PMID- 9542247
TI  - [Treatment review in rhinocerebral mucormycosis].
AB  - The rhinocerebral mucormycosis is the more common form produced by Rhizopus, a
      genus of fungi. It's a serious infective disease with high mortality, that needs
      a precocious medical treatment. Amphotericin B is the choice medical treatment,
      but liposomal amphotericine B in recent years is a better drug, due to minor
      renal toxicity and greater tisular diffusion. Even can not to treat all affected
      areas it's necessary an extensive surgical treatment according to individual
      characteristics and disease evolution. A 56-year-old man with rhinocerebral
      mucormycosis, caused by Rhizopus, who was treated with liposomal-amphotericin B
      and extensive rhino-orbital surgery is presented.

PMID- 9542248
TI  - Encephalocele with spontaneous CSF otorrhea.
AB  - Spontaneous encephalocele of the temporal bone is an uncommon condition (37 cases
      to date) associated with cerebrospinal fluid otorrhea. It results from a
      congenital dehiscence of the tegmen tympani and tegmen mastoideum. The AA. report
      3 additional cases and review methods for diagnosing and surgical treatment.

PMID- 9542249
TI  - [Cartilaginous tumors of the larynx. A report of 3 cases].
AB  - Cartilaginous tumours of the larynx are very seldom encountered. Worldwide
      literature report until now no more than 250 cases. The greatest number of cases
      (72%) are benign and localized on cricoid cartilage. They are characterized by
      its slow pace spread and chondrosarcomata shows scant tendency to metastasize,
      prevailing, instead, local increase. Best treatment resulted the conservative
      surgery. We report 3 cases (1 chondroma and 2 low ranked chondrosarcomata)
      diagnosed and treated in our Hospital in the last 15 years. Clinical and
      anatomopathologic features are exposed and the management as well, and also the
      postoperative course of each patient.

PMID- 9542250
TI  - [Tympanic chemodectoma. A report of 2 cases].
AB  - Report of 2 chemodectoma cases diagnosed in the ENT-Department (Prof. Labella) at
      C.H.U.S. The condition could be suspected because a tinnitus aurium and the
      transtympanic reddish image by otoscopy. And diagnosis settled through imaging
      techniques (computed tomography, magnetic resonance and selective angiography).
      Surgical treatment.

PMID- 9542251
TI  - [Lectin-mediated histochemical study of submucous glands of the normal nasal
      mucosa].
AB  - We have performed an histochemical study with lectins of the normal nasal mucosa
      of 6 patients. These patients were admitted at the Hospital for abdominal
      surgery. A wide biopsy was taken of the inferior nasal turbinate mucosa. The
      results show a different reactivity between the serous and mucous cells of the
      submucosal glands and with the goblet cells. We have not found reactivity to DBA,
      SBA and LTA lectins.

PMID- 9542252
TI  - Diabetes in pregnancy: state of the art in the Mediterranean countries, Portugal.
AB  - In Portugal since 1980 the health care for diabetes in pregnancy has begun to be
      specialised and centralised, and the care is provided by multidisciplinary teams.
      At present there are eight diabetic teams in the main cities in the North, Centre
      and South of the country: three in Oporto, two in Coimbra, two in Lisbon and one
      in Almada. In our Center of the University Hospital, Coimbra, from 1980 to 1992
      neonatal mortality dropped from 110/1000 to near 0/1000, macrosomia from 55% to
      20%, neonatal hypoglycemia from 28% to 5.6%, RDS from 26% to 2.5%, congenital
      malformation from 9% to 2%. A "consensus on diabetes and pregnancy" to implement
      and give uniformity to health care was recently done (1996): a) criteria for
      pregnancy planning and management for pregestional diabetes (type 1 and 2) have
      been given; b) protocol of screening, diagnosis and management for gestational
      diabetes have been suggested; c) finally a recent (1995) epidemiologic report of
      a multicentric Portuguese survey has been reported.

PMID- 9542253
TI  - Congenital malformations in infants of 517 pregestational diabetic mothers.
AB  - To determine whether the maternal metabolic control and/or the use of
      hypoglycemic drugs during early gestation is associated with a risk of congenital
      malformations, beginning on January 1989 to December 1994, clinical data from 16
      Italian centers were collected retrospectively and entered in a computerized data
      base: 517 pregnant women with pregestational diabetes mellitus, 362 with insulin
      dependent diabetes mellitus (IDDM) (mean age 28.13 +/- 4.8 years), 130 with non
      insulin-dependent diabetes mellitus (NIDDM) (mean age 33.01 +/- 5.32 years) and
      25 with impaired glucose tolerance (IGT) (mean age 32.48 +/- 6.2 years). The
      percentage of congenital malformations in NIDDM that took oral hypoglycemic drugs
      was 11.6% respect to 1.4% of NIDDM that did not take hypoglycemic drugs (p <
      0.01) and 3.7% of IDDM. Fasting blood glucose, glycosylated hemoglobin and urine
      keton bodies were more elevated in IDDM respect to NIDDM (p < 0.005). The
      percentage of malformations in offspring of NIDDM mothers is higher with respect
      to that of IDDM women, in spite of a better metabolic control.

PMID- 9542254
TI  - Diabetic pregnancy in over 35 years old women.
AB  - 87 pregnancies in diabetic women older than 35 years at time of conception were
      studied. 3% were insulin-dependent diabetes mellitus (IDDM), 52% non insulin
      dependent diabetes mellitus (NIDDM) and 45% gestational diabetes mellitus (GDM).
      Mean age was 38 +/- 3 years; BMI was 33.2 +/- 7.0 kg/m2; gestation rate was 5 +/-
      3 and number of alive children was 2 +/- 2. Only 3% of pregnancies were planned.
      Mean time of reference to diabetic care unit was 17 +/- 10 weeks. 95% of the
      women required human insulin. Mean total daily insulin dose was 0.49 +/- 0.28
      UI/kg/d, increasing with gestational age. Mean fasting glycemia was 6.85 +/- 1.93
      mmol/l and mean post-prandial glycemia was 8.29 +/- 2.52 mmol/l. Mean time of
      delivery was 38 +/- 2.1 weeks (less than 37 weeks in 9%). Cesarean section was
      performed in 44% of 34 cases. Death in utero occurred in 11% of 54 cases,
      postnatal death in 4%, congenital malformations in 4%, macrosomia in 40%. 9% of
      infants received intensive neonatal care. No difference was found between NIDDM
      and GDM about outcome of pregnancy. These results underlined importance of early
      screening for GDM as most cases seem to be undiagnosed pregravid diabetes
      mellitus (DM).

PMID- 9542255
TI  - Diabetes in pregnancy.
AB  - Despite the dramatic decline in maternal and perinatal morbidity and mortality
      over the past few decades, controversy still exists regarding the care of
      pregnant women with both pregestational and gestational diabetes mellitus.
      Carbohydrate intolerance is the most common metabolic complication of pregnancy.
      A review of the literature over the last two decades indicates that the incidence
      of gestational diabetes mellitus (GDM) varies from 0.15-12.3%. Between 0.2 and
      0.3% of pregnancies occur in women with insulin dependent diabetes mellitus
      (IDDM). When not diagnosed and treated properly, diabetes in pregnancy is
      associated with adverse maternal and fetal outcome; such as high perinatal
      wastage, congenital anomalies, macrosomia, and neonatal, childhood and adult
      complications. The main problems regarding maternal-fetal outcome in pregnancy
      complicated by diabetes can be divided into three main categories: the
      pathophysiology of the metabolic state in pregnancy and its implications on the
      mother and the conceptus. This presentation dealing with feto-maternal outcome of
      these high risk pregnancies will discuss accelerated fetal growth, congenital
      anomalies, future obesity and diabetes in babies born to GDM and pre-GDM mothers
      and future maternal diabetes in GDM and vascular complications in pre-GDM. Our
      organized team approach combined with intensive monitoring and therapy throughout
      pregnancy which has achieved successful results in women with complicated
      diabetes will be presented.

PMID- 9542256
TI  - Reclassification after delivery of diabetes in pregnancy.
AB  - Gestational diabetes mellitus (GDM) constitutes a risk factor for the development
      of non insulin-dependent diabetes mellitus (NIDDM). The search for parameters to
      provide discrimination between a high risk and a low risk for future development
      of NIDDM is today the aim of many investigations. The absence or presence of
      several factors such as glycemia during pregnancy and post partum, the need for
      insulin treatment, disorders of the pancreatic insulin secretion, the number of
      pregnancies, maternal obesity, the early diagnosis of GDM, the family history of
      diabetes mellitus, the race and immune disorders give rise to a very high
      relative risk (RR) of developing NIDDM. To know the degree of risk will allow a
      future appropriate clinical intervention to reduce the incidence of NIDDM and its
      economic cost.

PMID- 9542257
TI  - Delivery in diabetic pregnancy.
AB  - Two hundred and twenty deliveries of diabetic pregnant women, occurring from 1990
      1994 were studied: 186 gestational (GDM) and 34 pregestational diabetes (PGDM).
      Women who delivered during the year of 1994 were considered as control population
      (3615 births). Mode of delivery, planned delivery, delivery's gestational age,
      shoulder dystocia, macrosomia and large for gestational age (LGA) were
      investigated. Cesarean section and planned delivery were respectively 39% vs
      20.5% and 51.6% vs 16% respectively in diabetic vs control women. Deliveries
      after 40 weeks were 29% in GDM, 3% in PGDM and 50% in control women. Macrosomia
      occurred in 17.7% of diabetic against the 8% of controls. Finally shoulder
      dystocia occurred in the 3.6% of diabetic women against the 0.3% of the control
      group. These data indicate that in our diabetic population there is a high rate
      of cesarean sections and planned deliveries, as well as macrosomia, LGA and
      shoulder dystocia. Obstetric decision to allow the delivery to term or near term
      was not enough to bring the rate of macrosomia and LGA close to the normal, which
      can be consequence of the diabetic control in pregnancy, in spite of intensive
      care intervention.

PMID- 9542258
TI  - Does preconceptional counselling in diabetic women influence perinatal outcome?
AB  - We aimed to assess the impact of a preconceptional clinic (PC) on the perinatal
      outcome (PO) of diabetic pregnancies attended in our centre. We studied 185
      pregnancies attended in the 1986-1996 period (152 in women with insulin dependent
      diabetes mellitus (IDDM) and 33 with non insulin-dependent diabetes mellitus
      (NIDDM)) and we analysed the perinatal outcome for both mother and fetus. Sixty
      six women (36.1%) had enrolled in the PC, 41.4% for IDDM and 9.1% for NIDDM
      pregnancies, p < 0.01. First pregnancy HbA1c (in SD around the mean) was 3.98 +/-
      3.00 in non-attenders (NA) vs 2.57 +/- 2.41 in attenders (A), p < 0.01. The final
      HbA1c was in the normal range in both groups. D-R class according to White
      classification was 33.0% for NA vs 54.5% for A, p < 0.01. There were no
      differences in the rates of abortion and major malformations (8.8% NA vs 3.6% A,
      ns). Both groups differed in the rate of cesarean sections (54.9% NA vs 71.0% A,
      p < 0.05) and in the rate of small for gestational age infants (SGA) (8.7% NA vs
      1.8% A, p < 0.05). There were no differences between groups in maternal or
      neonatal outcomes. In this group of diabetic women with a moderate although less
      than optimal metabolic control at the beginning of pregnancy, the impact of PC on
      PO is less evident than described.

PMID- 9542259
TI  - Blood pressure monitoring in diabetic pregnancy.
AB  - Hypertensive disorders which complicate 5-10% of all pregnancies are more
      frequent in diabetic women. We longitudinally monitored blood pressure (BP) for a
      24 h period in 54 diabetic out patients, at each trimester of pregnancy, in order
      to observe the relationship between the blood pressure behaviour and the main
      clinical features of these subjects. A relationship was found between blood
      pressure and the diabetes type. In insulin-dependent diabetes mellitus (IDDM)
      women, the age of diagnosis and the diabetes duration played the major role
      whereas, in non insulin-dependent diabetes mellitus (NIDDM) women only the
      patients' age was correlated with the BP levels. Higher BP levels were found in
      women belonging to the White class D, and whose diabetes duration was more than
      10 years. An interesting correlation was also demonstrated between BP and insulin
      requirement, in late pregnancy as well as the time of delivery. Early in
      pregnancy, BP levels, even if within normal range, were undoubtedly higher in
      those women who developed hypertension compared to those who continued to be
      normotensive. Daytime BP values were always found higher than night-time BP
      values but, the physiological biorhythm seemed to be altered at the end of
      pregnancy.

PMID- 9542260
TI  - Diabetes and pregnancy: prophylaxis of genital infections.
AB  - Diabetic pregnant women have many potential reasons to have genital infections
      such as poor metabolic control and impairement of leucocyte function. Relative
      immune deficiency exists in pregnancy. This study was designed to test the
      hypotheses that pregnant patients with insulin-dependent diabetes have a higher
      rate of ante partum genital infections when compared with a pair-matched control
      population. Two groups of pregnant women consisting of 23 patients with and 23
      without diabetes mellitus, underwent colposcopy and cytology between 16th and
      24th week of gestation to detect the presence of human papilloma virus (HPV),
      Gardnerella vaginalis, Candida albicans and aspecific infections. No significant
      differences were observed between the two groups.

PMID- 9542261
TI  - Telemedicine in the treatment of diabetic pregnancy.
AB  - Good diabetic control requires that treatment be continuously adapted to the
      patient behavior. We investigated whether the use of telemedicine could present
      an advantage to the management of the diabetic woman during pregnancy. A system
      completely automatic (DIANET system) was used. Twenty IDDM women participated in
      the study: 10 treated by telemedicine and 10 by conventional system, at times
      "entry" (9.5 weeks), "basal" (9.5-16.8 weeks), "1st month" of investigation, and
      "end" (near delivery). All women used intensified protocols of insulin
      administration. The treatment with DIANET vs conventional showed a better
      metabolic control as estimated by profile of blood glucose absolute values (at
      time "end": values significantly lower before breakfast: 87 +/- 6 vs 104 +/- 4
      mg, lunch: 85 +/- 5 vs 104 +/- 4 mg, and after dinner: 102 +/- 5 vs 124 +/- 6
      mg). These results were associated with higher insulin doses in the DIANET vs
      conventional treatment, and a significant reduction of hypoglycemic reaction in
      both group. Our results suggest that telemedicine-DIANET is a practical way of
      providing specialist care in the pregnancy area.

PMID- 9542262
TI  - Pathophysiology of diabetes in pregnancy.
AB  - Pregnancy is attended by extensive hormonal readjustments on the part of the
      mother. Almost every endocrine tissue participates in adaptive changes that
      maintain the metabolic state of the woman during normal pregnancy. Endocrinologic
      and metabolic adaptations characterizing pregnancy in women with normal
      carbohydrate metabolism also impinge upon the metabolism of the diabetic during
      pregnancy. In the diabetic woman the impairment of metabolism which follows the
      modifications of endocrinologic adaptations induces a compromised metabolic
      "milieu" in both the foetal blood and amniotic fluid in which swallows the fetus,
      promoting several damages according to the gestational age in the conceptus.
      Disturbances of intermediary metabolism undoubtedly play a major role in the
      etiology of complications of diabetic pregnancy. However an increasing amount of
      evidence is accumulating that suggests that abnormalities of immune function may
      also be operative in both the mother and fetus as well as in placenta. Finally
      there is limited information on the long-term prognosis of infants born to
      mothers with pre-gestational and gestational diabetes mellitus. Follow-up studies
      have mainly focused on two aspects: the risk of appearance of diabetes later in
      life, and psychosomatic development. Genetic aspects and the role of metabolic
      disorders during pregnancy must be once again emphasized.

PMID- 9542263
TI  - Glucose transporters (GLUT 1, GLUT 3) mRNA in human placenta of diabetic and non
      diabetic pregnancies.
AB  - Glucose transporters (GLUT) catalyse the transport of glucose in many human
      tissues, including the placenta. On the other hand glucose concentrations can
      affect both glucose transport activity and level of GLUT mRNA and protein. Up to
      now very few studies, concerning GLUT in the placenta appeared and studies in
      vivo in human diabetic pregnancy are lacking. Therefore we investigated placental
      GLUT 1 and GLUT 3 mRNA in 10 diabetic (5 IDDM, 2 NIDDM, 3 GDM) and 9 non-diabetic
      women. GLUT 1 mRNA was found significantly correlated with maternal age (> 30 vs
      < 30 years: p < 0.025), with placental weight (> 575 vs < 575 g: p < 0.05), while
      GLUT 3 mRNA decreased significantly in late gestation of diabetic women (38-40 vs
      < 38 weeks: p < 0.025). In addition GLUT 3 was significantly lower in the
      diabetic than in non-diabetic women in late gestation. These preliminary results
      deserve to better elucidate feto-maternal carbohydrate metabolism at the
      placental level in normal as well as diabetic pregnancy.

PMID- 9542264
TI  - Na(+)-H+ exchange activity throughout pregnancy: the proper experimental
      approach.
AB  - Pregnancy is associated with a 30-50% rise in cardiac output and a close to 50%
      increase in blood volume. The Na(+)-H+ exchanger is a key mediator of tubular
      NaCl absorption and a stimulus-response coupling mediator. We measured
      erythrocyte Na(+)-H+ exchange activity over the course of normal pregnancy in 18
      healthy pregnant women (mean age 32 +/- 4 years) at 14, 24 and 33 weeks of
      gestation and 15 nonpregnant healthy women (mean age 32 +/- 9 years). No
      pregnancy was complicated by hypertension. Serum urea, creatinine and sodium did
      not change through gestation, while serum potassium slightly but significantly
      decreased. Urinary excretion rates of both sodium and potassium remained
      unchanged. Urea and creatinine clearances were constantly elevated in pregnant vs
      non-pregnant control women. Erythrocyte Na(+)-H+ exchanger reached the highest
      activity at about the 14th week of gestation, when cardiac output also peaked.
      Thereafter, it tended to decrease, yet remaining above the normal values until
      the 34th week. Conceivably, the observed hyperactivity of the transporter may be
      a contributing factor to the hemodynamic adjustments attending to normal
      pregnancy.

PMID- 9542265
TI  - Levels of advanced glycosylation end-products (AGE) in sera of pregnant diabetic
      women: comparison between type 1, type 2 and gestational diabetes mellitus.
AB  - The chronic hyperglycemia can lead to an increase of the advanced glycosylation
      end-products (AGE) levels on proteins and macromolecules. Abnormal levels of AGE
      in several tissues has been associated with the pathogenesis of late diabetic
      complications. In diabetic pregnant women, high AGE levels might influence the
      delicate maternal-fetal balance and therefore alter the pregnancy outcome. In
      this preliminary study, we have measured the AGE in sera of 44 diabetic women in
      two trimester. Sixteen sera from non diabetic pregnant women have been used as
      controls. The AGE have been analyzed by means of an ELISA method with an
      antiserum anti-RNAse-AGE, produced in the Laboratory of Clinical Biochemistry of
      the Istituto Superiore di Sanita. Diabetic patients type 1 and type 2, in good
      metabolic control, showed normal AGE levels at both trimester. Patients with
      gestational diabetes showed significantly high serum AGE levels (p < 0.05). A
      more extended study will give better insight on the association between AGE
      levels and a physiopathology of diabetic pregnancy.

PMID- 9542266
TI  - IGF-1 levels in diabetic pregnant women and their infants.
AB  - Plasma IGF-1 was measured in 38 diabetic pregnant women (DPW) and in 12 non
      diabetic pregnant women (NDPW) during the 1st, 2nd and 3rd trimester of
      pregnancy. IGF-1 was measured in the cord blood of 24 infants of diabetic mothers
      (IDDM) and IGF-1 in 11 infants of non diabetic mothers (NIDDM). A progressive and
      significant (p < 0.0001) increase of IGF-1 values was found throughout the
      pregnancy both in DPW and NDPW IGF-1 (149 +/- 18 ng/ml vs 181 +/- 14 ng/ml, 184
      +/- 17 ng/ml vs 232 +/- 25 ng/ml, 279 +/- 20 ng/ml vs 325 +/- 17 ng/ml).
      Furthermore IGF-1 decreased significantly soon after delivery in both groups of
      women. In type 1 diabetic pregnant women IGF-1 values were significantly lower
      than the controlled non diabetic patients. IGF-1 in the cord blood was
      significantly higher in IDDM than in NIDDM 86 +/- 7 ng/ml and 62 +/- 7 ng/ml
      respectively (p < 0.03). In addition, DPW plasma levels IGF-1 were positively
      correlated with the weight of the placenta (r = 0.233, p < 0.03) and negatively
      correlated with the diabetes duration (r = 0.412, p < 0.05). No correlations were
      found between IGF-1 cord blood concentrations and gestational age, birth weight
      and length, but there was a significant correlation with weight percentile (r =
      0.846, p < 0.001). No correlation was found between maternal IGF-1 plasma levels
      and other parameters like insulin need, weight gain, metabolic control and time
      of delivery.

PMID- 9542267
TI  - A protocol of screening of gestational diabetes mellitus.
AB  - We evaluated GDM frequency in the Padua area. 490 non-diabetic pregnant women
      were divided into group A (234), with at least one GDM risk factor, and group B
      (256), with no risk factors. Group A underwent this screening program with oral
      glucose challenge test (OGCT) and OGTT when OGCT was positive at 10-14th
      gestational week (gw), at 24-28th gw and at 30-34th gw. Group B underwent the
      same screening starting at 24-28th gw. 46.9% of the pregnant women had positive
      OGCT with higher frequency in group A (group A vs group B p < 0.01). GDM
      prevalence in all women was 10.8% with higher frequency in group A women (group A
      vs group B p < 0.01). The anticipation of the screening at the first trimester of
      pregnancy in group A women allowed early diagnosis of 11.6% of GDM. Regarding
      maternal and fetal outcome the only significative differences between GDM and non
      GDM were prevalence of macrosomia and of cesarean sections.

PMID- 9542268
TI  - Screening of gestational diabetes in Tuscany: results in 2000 cases.
AB  - According to the guidelines of the "Third international workshop conference on
      GDM", we have examined 2000 pregnant women. The glucose challenge test (GCT) was
      positive in 408 cases (20.4%) and negative in 1592 (79.6%). The OGTT (Carpenter
      and Coustan's criteria) was performed in 647 pregnant women. GDM and IGGT
      prevalence was of 6.25% and 5.5% respectively and normal glucose tolerance (NGT)
      88.25%. The GCT effectiveness for GDM and IGGT diagnosis is: sensibility 75.1%,
      specificity 44%, positive predictive value 46.4% and negative predictive value
      74%. GDM and IGGT compared with NGT women were significantly older (p < 0.05) and
      prepregnancy BMI was higher (p < 0.01); the prevalence of previous macrosomia (p
      < 0.01), previous gestational diabetes (p < 0.01) and family history for diabetes
      mellitus (p < 0.05) was greater in GDM and IGCT. The prevalence of preterm
      delivery was higher in both GDM and IGCT (GDM 12.5% and IGGT 15.4% vs NGT 6%; p <
      0.01), as well as the prevalence of cesarean sections (GDM 31.6% vs IGGT 23.5%
      and NGT 20.3%; p < 0.02), and the occurrence of macrosomia (GDM 27.6%, IGGT 16.6%
      and NGT 16.2%). In addition a higher prevalence (p < 0.01) of
      hyperbilirubinaemia, hypoglycemia and hypertrophy cardiomyopathy was observed in
      newborns from GDM women. Our data show that: GCT has a good specificity for GDM
      diagnosis, prevalence of GDM in our population is about 6%, GDM is still
      correlated to an elevated maternal and neonatal morbility.

PMID- 9542269
TI  - Should we treat minor degrees of glucose intolerance in pregnancy?
AB  - We examined the pregnancy outcome of 112 women classified as minor degrees of
      glucose intolerance (MDGI) in pregnancy in a screening program based on Carpenter
      and Coustan's criteria. The MDGI group comprised 49 women with abnormal oral
      glucose challenge test (OGCT) followed by normal OGTT (group A), and 63 with
      "borderline" OGTT (1 abnormal value, group B). No treatment was offered to 88
      MDGI women, while 26 received dietary advice and metabolic monitoring. A control
      group was constituted from 112 age- and BMI-matched negative screenees. Similar
      rates of cesarean sections and macrosomia, but higher rate of large for
      gestational age (LGA) babies (25.9% vs 14.3%) were found in MDGI, without
      difference between groups A and B. When comparing treated and untreated MDGI,
      lower LGA incidence (11.5% vs 30.2%) and no macrosomia were found in the former.
      In conclusion, untreated MDGI may present excessive fetal growth, which can be
      normalized by dietary treatment and metabolic monitoring.

PMID- 9542270
TI  - Gestational diabetes mellitus (GDM) and macrosomia: a controversial story.
AB  - Increased perinatal morbidity-mortality are associated with gestational diabetes
      mellitus (GDM). We studied 69 non-diabetic pregnancies (age 30 +/- 5 years) by
      repeating oral glucose tolerance test (OGTT, 100 g; area under glycemic, AUGC as
      g min/dl, and insulinemic, AUIC as mU min/ml, curves were calculated) and HbA1c
      measurement at 14, 24 and 33 weeks. In the 3rd trimester, 7 women had abnormal
      OGTT, but none of the 12 mothers of large babies (> 3.9 kg) had GDM. Among 15
      pregnants with basal body mass index (BMI) > 25 kg/m2, 2 developed GDM, 5 had
      babies > 3.9 kg, 8 had normal birthweight babies. Those pregnants who showed
      after-load hyperglycemia despite normal insulin secretory response (insulin
      resistance) developed GDM, but delivered normal birthweight babies. Large
      neonates were delivered from women with the greatest both gestational weight gain
      and insulin sensitivity, but normal glucose tolerance. The heaviest pregnants
      with normal both glucose tolerance and insulin sensitivity had normal weight gain
      and normal birthweight infants. Neonatal body weight was correlated with maternal
      gestational weight gain, placental weight, 3rd trimester AUIC/AUGC ratio and 1st
      2nd trimester HbA1c.

PMID- 9542271
TI  - Predictive factors for insulin treatment in women with diagnosis of gestational
      diabetes.
AB  - To evaluate if at diagnosis some factors are predictive of the insulin treatment,
      75 pregnant women with gestational diabetes mellitus (GDM) and 75 with normal
      glucose tolerance were examined. The GDM group underwent a diet containing 25
      kcal/kg/24 h and insulin was started when fasting and 2 h after meals glucose
      levels were respectively > 95 and > 125 mg/dl. 52 patients were treated with diet
      (GDd) and 23 with diet and insulin (GDi). Diagnosis week, prepregnancy body mass
      index (BMI), weight gain, glucose levels during oral glucose tolerance test
      (OGTT) (0', 60', 120' and 180'), area under curve (AUC), triglyceride levels and
      infant weight at delivery were evaluated. Triglyceride levels were higher in GDi
      respect to NGT group (232.2 +/- 110.7 mg/dl vs 147.4 +/- 70 mg/dl; p < 0.001).
      Diagnosis was earlier and 180' glucose levels, AUC and BMI were higher in GDi
      than GDd group. In conclusion, triglyceride and 180' glucose levels, AUC,
      pregestational BMI and diagnosis week are predictive factors for insulin
      treatment in gestational diabetes.

PMID- 9542272
TI  - Gestational diabetes: clinical characteristics and birth weight.
AB  - This retrospective study investigates the clinical characteristics of gestational
      diabetes mellitus (GDM) (time of diagnosis, different treatment, metabolic
      parameters, etc.) in relation to prepregnancy body mass index (BMI) and the
      influence of BMI on neonatal outcome. 93 GDM women and 110 control subjects were
      divided into three groups in relation to their prepregnancy BMI: normalweight
      (Nw), overweight (Ow) and obese (Ob). GDM was diagnosed significantly (p < 0.01)
      earlier in Ow and Ob than in Nw. Preterm deliveries and cesarean sections
      resulted significantly (p < 0.01) increased in all BMI categories of GDM respect
      to matched controls. Prevalence of neonatal macrosomia was higher in GDM patients
      (44.6%) compared with normal controls (15.4%) and correlated (p < 0.01) with
      prepregnancy BMI in both groups. Nevertheless in each BMI category the prevalence
      of macrosomia was significantly higher in GDM patients. The body weight increase
      during pregnancy was not associated with neonatal macrosomia. This study shows
      that prepregnancy BMI is an important risk factor for GDM and is predictive for
      macrosomia specially in women suffering from GDM.

PMID- 9542273
TI  - Lipid metabolism alterations in patients with gestational diabetes mellitus
      associated fetal macrosomia.
AB  - Fetal macrosomia is commonly associated with gestational diabetes mellitus (GDM)
      which may lead to various complications. It has been suggested that some other
      metabolites apart from maternal hyperglycemia are responsible for the genesis of
      macrosomia. Lipid metabolism changes in GDM patients having macrosomic fetuses
      were studied. A lipid tolerance test (10% Lipovenous solution) was performed in
      14 GDM. Pre- and post-infusion plasma lipid levels and their elimination rates
      were measured and compared to the ones of 8 non diabetic control pregnant women.
      HbA1c, basal glucose and triglyceride levels were found to be higher in GDM group
      and significantly higher levels of triglycerides persisted throughout the
      infusion. FFA, glycerol and phospholipid levels increased following infusion in
      both groups without significant differences. Glucose, C-peptide and insulin
      levels remained unchanged after the infusion. Increased basal triglycerides with
      slowed triglyceride metabolism may be responsible for the fetal macrosomia in
      mild GDM patients whose fasting blood glucose are below 105 mg/dl. A better
      metabolic control that provides plasma lipid regulation as well as glucose
      control may forestall the occurrence of fetal macrosomia.

PMID- 9542274
TI  - The "Sardinia-IDDM study": an attempt to unravel the cause of insulin-dependent
      diabetes mellitus in one of the countries with the highest incidence of the
      disease in the world.
AB  - Sardinia and Finland have the highest incidence of IDDM in the world. Thus, both
      regions represent ideal observatories for investigating the environmental,
      genetic and immunological factors, which have led to this dramatic increase. We
      have concentrated our efforts in Sardinia. Among several projects, there is the
      mapping of the Island for hot and cold spots for overt IDDM. In order to map the
      Island for pre-IDDM, we have collected and bled around 10,000 school children
      (age 6-14 years) and we are now in the process to enroll around 30,000 newborn.
      We report here our initial results, which show that progression to IDDM is
      accompanied in both cohorts by the presence of a combination of ICA with either
      GAD and IA-2 antibodies or both. This approach should lead to design reliable
      models of IDDM prediction in the general population, which will benefit an early
      insulin treatment and, hopefully, an effective prevention of the disease.

PMID- 9542275
TI  - Autoimmune markers of diabetes in diabetic pregnancy.
AB  - Gestational diabetes mellitus (GDM) has been described in 1-3% of pregnancies and
      increases the risk (up to 60-70%) to subsequently developing an overt diabetes
      (generally of type 2 non insulin-dependent diabetes mellitus (NIDDM)). Several
      humoral autoimmune phenomena have been described in GDM: islet cell antibodies
      (ICA) have been found and it was shown that ICA+ patients tend to have a worse
      glucose tolerance. Recently, autoantibodies against glutamic acid decarboxylase
      (GAD), were detected in type 1 diabetic sera before or at the onset of the
      disease; these markers, as well as ICA and insulin antibodies, seem to have a
      predictive value for the onset of the disease. Aim of our study was to
      investigate the presence of GAD65 in 83 GDM, 79 NIDDM and 64 pregnant normal
      women in late gestation. GAD Ab positivity was found (0.035 index as limit) only
      in GDM and NIDDM (3.6% in GDM, 3.8% in NIDDM, and nothing in control women).
      These results indicate that GAD positivity in GDM overlaps that of NIDDM,
      suggesting that the two diabetic populations have the same predisposition to
      develop a type 1 diabetes mellitus, and likely they share the same disease.
      Further studies need to clarify whether this prevalence of GAD positivity may
      unmask type 1 diabetes in both GDM and NIDDM diabetic women.

PMID- 9542276
TI  - A study on lymphocyte subpopulations in diabetic pregnant women and their
      newborn.
AB  - We studied the lymphocyte subpopulations in 14 pregnant women with type 1 insulin
      dependent diabetes mellitus (IDDM), mean age (+/- SD) 30 +/- 4 years, mean
      disease duration 12 +/- 5 years, in 14 with gestational diabetes mellitus (GDM)
      (mean age 33 +/- 6 years) and 21 matched healthy pregnant controls (C), when the
      subjects delivered, and in their newborn. The GDM and IDDM mothers show a
      significant increase (p < 0.05) of lymphocytes in comparison with C (GDM 1.83 +/-
      0.5 x 10(9)/l, IDDM 1.6 +/- 0.68 x 10(9)/l, C 1.06 +/- 0.45 x 10(9)/l
      lymphocytes), which has repercussion on lymphocyte subpopulations absolute
      values. The newborn of GDM mothers have an increase of lymphocytes T-activated
      (0.6 +/- 0.3 vs 0.3 +/- 0.2%; p < 0.05) and a reduction of NK lymphocytes than C
      (8.9 +/- 9 vs 15.5 +/- 7.6%; p < 0.05). The newborn of IDDM mothers show a
      significant reduction of NK lymphocytes than C (10 +/- 6 vs 15.5 +/- 7.6%; p <
      0.05). So in newborn of diabetic mothers there is a deficit of natural immunity
      at birth which has to be evaluated by follow-up study.

PMID- 9542277
TI  - Target antigens in autoimmune diabetes: pancreatic gangliosides.
AB  - Type 1 diabetes mellitus is a disease caused by the autoimmune destruction of
      insulin-producing pancreatic beta-cells that takes place in genetically
      prodisposed individuals. Autoantibodies and autoreactive T lymphocytes reacting
      with islet target molecules or protein of 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. As far as autoantigens of
      glycolipid nature is concerned, gangliosides such as GT3, GD3 and especially GM
      1, have been shown to be target of autoantibodies associated to autoimmune
      diabetes. Of particular interest is the islet-specific monosialo-ganglioside GM2
      1, which is target of an autoimmune response highly associated to future
      progression to diabetes development in first degree relatives of type 1 diabetic
      individuals. This molecule is recognized by IgG autoantibodies which have been
      detected before the appearance if clinical diabetes both in man and in the NOD
      mouse, representing a novel marker of beta-cell autoimmunity.

PMID- 9542278
TI  - Autoimmune thyroid disease and insulin-dependent diabetes mellitus during
      pregnancy and post partum.
AB  - The aim of this study was to assess thyroid dysfunction and autoimmunity in
      pregnant insulin-dependent diabetes mellitus (IDDM) women during pregnancy and
      early post partum. Fifteen pregnant IDDM women and 77 healthy pregnant women were
      studied. Free T4, TSH, TPO-Ab and Tg-Ab were assayed during the first and third
      trimester of pregnancy and 3 months post partum. In IDDM women FT4 levels
      significantly decreased (p < 0.05) during third trimester and 3 months post
      partum and also TPO-Ab during third trimester (p < .01). 26% of IDDM and 4% of
      the controls presented post partum thyroid dysfunction. We recommend that
      prepregnant IDDM be screened for TPO-Ab. Those with a positive result would be
      followed with serial monitoring of free T4 and TSH levels during each trimester
      as well as during the post partum period.

PMID- 9542279
TI  - Influences of thyroid diseases in diabetic pregnant women.
AB  - Thyroid disorders are particularly frequent in women and, second to diabetes
      mellitus, are the most common endocrine diseases during pregnancy. An association
      between insulin-dependent diabetes mellitus and thyroid autoimmunity has long
      been recognized. Management of thyroid diseases in pregnancy is different than in
      non pregnant women, due to physiological changes of thyroid hormone economy in
      the childbearing period. Thyroid dysfunction may affect carbohydrate metabolism
      and worsen glucose control in diabetic patients. On the other hand, poorly
      compensated diabetes mellitus may cause alteration in the production and
      metabolism of thyroid hormones. Pregnant women with insulin-dependent diabetes
      mellitus have an increased risk of developing post partum thyroiditis. These
      observations have lead to the recommendation that thyroid function should be
      checked in diabetic women during pregnancy and in the post partum.

PMID- 9542280
TI  - Thyroid autoimmunity in pregnant women at risk for GDM.
AB  - Presence of antithyroid autoantibodies (ThyAb) during pregnancy is strictly
      related to the risk of developing post partum thyroiditis (PPT) and this risk is
      increased in IDDM pregnant women. Gestational diabetes mellitus (GDM) is defined
      as carbohydrate intolerance of variable severity that begins, or is first
      diagnosed, during pregnancy. GDM is considered a risk factor for both type 1 and
      type 2 diabetes and various non-organ specific autoantibodies have been found to
      be associated with GDM, although there is little information on the association
      of GDM with thyroid autoimmunity. In this study oral glucose tolerance and
      prevalence of ThyAb were evaluated in a group of 41 pregnant women at increased
      risk of developing GDM and in a healthy control group. Our results showed that
      22% of GDM risk group had impaired glucose gestational tolerance (IGGT) or GDM at
      the time of oral glucose tolerance test (OGTT). Moreover, ThyAb prevalence found
      in the women at increased risk of GDM (14.6%) was similar to that observed in
      healthy pregnant controls (12.5%). Nevertheless ThyAb frequency was higher in
      those GDM risk women with family history of diabetes (30.7%).

PMID- 9542281
TI  - The 6 volt battery for implantable cardioverter/defibrillators.
AB  - The usage of a 6 V lithium manganese dioxide battery results in a significant
      reduction of capacitor loading time within implantable
      defibrillators/cardioverters. In order to provide ERI indication a new cathode
      formulation has been developed. The battery shows no voltage delays, a low self
      discharge and fulfilled all requirements to an energy source for an implantable
      device.

PMID- 9542282
TI  - [Possibilities and limits of automatic detection of pathologic intracranial
      pressure waves with FFT].
AB  - Owing to the existence of "reserve spaces" varying individually in extent and
      expressed by the term compliance, space-consumption intracranial processes do not
      raise the intracranial pressure (ICP) primarily. Only when this compliance has
      been exhausted may ICP rise dramatically and may rapidly reach dangerously high
      levels. It has been shown in the past that "anticipatory" initiation of ICP
      reducing measures--i.e. very early in the development of increasing mean ICP--may
      greatly benefit patient outcome. To recognize an imminent ICP crisis, the
      available compliance needs to be known. The classical method for determining this
      latter is the bolus test, which, however, has the disadvantage of being
      discontinuous and associated with the risk of infection. Another, less invasive
      and continuous, option is the recognition of pathological intracranial pressure
      waves. However, recognition of such patterns requires specialized knowledge, that
      is not widely available. Since, however, knowledge of the compliance is of
      general importance for intensive care, the idea of developing a PC-based
      automated system for the identification of pathological waves was followed up.
      During the course of our basic research effort, we investigated the suitability
      of the fast Fourier transformation (FFT) algorithm for this purpose. We were able
      to show that while the FFT is theoretically useful for the detection of
      pathological intracranial waves, its shortcomings in terms of its sensitivity to
      extraneous signals (noise) (of considerable importance for biological data
      handling) and errors in correctly estimating the amplitudes of pathological waves
      (of great importance for clinical evaluation) make FFT appear less than optimally
      suitable for this purpose.

PMID- 9542283
TI  - [Reduction of bacterial contamination during mechanical autotransfusion by uv
      irradiation--initial results].
AB  - OBJECTIVE: To investigate the effects of UV-radiation of autologous blood on
      bacteria and red blood cells when using intraoperative sampling of autologous
      blood using a cell separator--an established method for reducing the need for
      donor blood during surgery--which is reported to have a bacterial contamination
      rate of 5-75%, due mainly to coagulase-negative staphylococci (CNS). METHODS:
      Cell-separator blood was diluted to a haematocrit level permitting transmission
      of 1% of the UV-radiation used in this study (lambda 254 nm, coat thickness 1
      mm). CNS samples were irradiated for 2, 4, 10, 20 and 30 seconds. Free
      haemoglobin and methaemoglobin levels were measured, and erythrocytes examined
      microscopically at the end of the procedure. RESULTS: Blood samples had to be
      diluted to a haematocrit of 1% to permit transmission of 1% of the UV light. The
      optimal irradiation duration was 4 seconds, when bacteria were completely
      eliminated. Longer irradiation durations were associated with increasing levels
      of free haemoglobin and methaemoglobin, the levels of which at 4 seconds exposure
      were 12.5 mg/L and 15.5%, respectively. CONCLUSIONS: It is possible to prevent
      CNS contamination of cell-separator blood by irradiation with UV light. Prior to
      clinical application, however, the method will need to be modified to minimize
      side effects and increase its decontamination efficacy.

PMID- 9542284
TI  - [ISO 9001 conformity in research, teaching and rehabilitation].
AB  - Quality assurance, in particular in the areas of development and production of
      medical devices, is one of the tasks of biomedical engineering. The
      interdisciplinary working group "Functional Rehabilitation and Group Education,
      Vienna" is committed to the development and implementation of group education
      models on three levels: (1) direct education/instruction of patients with chronic
      diseases, (2) university research and teaching, and (3) development of technical
      aids for rehabilitation and the means for disseminating group education models in
      rehabilitation and therapy. Major aims were, by generating conformity with ISO
      9001 standards, to achieve greater transparency and process optimization with
      very small resources in university (teaching, research, technical aids) and extra
      university (rehabilitation) areas. A secondary aim was the establishment of
      interdisciplinary (clinical and biomedical) cooperation at university level. In
      all main areas (research, teaching and group education/instruction), ISO 9001
      conformity was achieved by our activities on three methodological levels: (1)
      description and analysis of processes, (2) use of ISO 9001 standards for
      evaluating internal processes, and (3) optimization measures. The following
      article contains relevant elements of the quality manual and quality assurance
      system, and offers a typical example of innovative cooperation between medicine
      and medical engineering.

PMID- 9542285
TI  - [Effect of prosthesis shaft coating on postoperative load bearing of the femur].
AB  - Stems and cups for total hip replacement (THR) must be coated with hydroxyapatite
      (HA), which enhances the osseo-integration of the implant. The aim of the present
      report was to investigate the basic influence of coating on the biomechanical
      situation, for example, the mechanical stress in the femur and at the femur
      implant interface. Using the finite element method, three types of stems for THR
      were investigated: non-coated, completely HA-coated, and proximally HA-coated.
      All three stems were of the same design, and had identical material properties.
      In addition, all other conditions were identical. The results show that, in terms
      of the nature of the coating, the HA-coated stem is biomechanical superior to the
      non-coated stem, and the proximally coated stem is superior to the completely
      coated stem.

PMID- 9542286
TI  - HIV-associated autoimmune hemolytic anemia complicated by pulmonary embolism
      following a red blood cell transfusion: case report and review of the literature.
AB  - BACKGROUND: Though positive direct antiglobulin tests are common in AIDS
      patients, overt hemolysis is rare. A hypercoagulable state has recently been
      recognized in these patients and may contribute to the thromboembotic
      complications previously reported in three patients with HIV-associated
      autoimmune hemolytic anemia. CASE REPORT: An AIDS patient with severe warm
      autoimmune hemolytic anemia developed a pulmonary embolus after a single red
      blood cell transfusion. CONCLUSION: There may be an increased risk of
      thromboembolism in AIDS patients with autoimmune hemolytic anemia who receive red
      blood cell transfusions, a concern we have previously raised. Prophylactic
      anticoagulation should be considered in this setting.

PMID- 9542287
TI  - Noxious fumes in a medical center: chemical and psychological aspects.
AB  - A group of operating room personnel at a medical center in Connecticut reported
      severe respiratory irritation manifested by either proxysmal cough or throat
      irritation suggestive of a noxious fume exposure, 13 April 1994. However,
      persistent complaints on 14 April 1994 were significantly different and more
      suggestive of a psychological reaction. By careful interviewing, physical
      examination, toxicological assays, and epidemiological investigation, the true
      nature of a mixed physiological and psychological episode was delineated.
      Enlightened management policy enabled rapid restoration of return to work with
      minimal economic loss.

PMID- 9542288
TI  - Clinical evaluation of hand-arm-vibration syndrome in shipyard workers:
      sensitivity and specificity as compared to Stockholm classification and
      vibrometry testing.
AB  - The hand-arm-vibration syndrome (HAVS) is a complex entity composed of
      circulatory, sensory, and motor disturbances, as well as associated
      musculoskeletal components. This study was performed to find a diagnostic testing
      modality with sufficient sensitivity, specificity, and predictive value to be
      utilized as a screening test for this disorder in a working population. A full
      range of testing modalities was utilized in the shipyard medical department. In
      addition, a clinical diagnosis of vascular and sensorineural disease was
      established in the workers by a combination of plethysmography, vibrometry, two
      point discrimination, and monofilament testing in an independent occupational
      medicine clinic. No one test modality met the requirements for such a definitive
      diagnostic test. Rather, a range of modalities was required to reach any
      acceptable level of predictive value, with sufficient degrees of specificity and
      sensitivity.

PMID- 9542289
TI  - Remifentanil (Ultiva).

PMID- 9542290
TI  - A community hospital's ambulatory addiction medicine program.

PMID- 9542291
TI  - Why not to invest in a publicly traded managed care company.

PMID- 9542292
TI  - "Slow down, you move too fast".

PMID- 9542293
TI  - The corporatization of the United States health-care system.

PMID- 9542295
TI  - In response to Physician assisted living (PAL)

PMID- 9542294
TI  - Should the city medical societies take an active part?

PMID- 9542296
TI  - In response to the physicians assisted living: the PAL partner initiative
      article.

PMID- 9542297
TI  - In response to Dr. Maria Lenaz's letter to the editor, "Ethics in managed care".

PMID- 9542298
TI  - In response to Dr. Maria Lenaz's letter to the editor, "Ethics in managed care".

PMID- 9542299
TI  - In response to Dr. Maria Lenaz's letter to the editor, "Ethics in managed care".

PMID- 9542300
TI  - In response to Dr. Richard Evans's Update on childhood asthma.

PMID- 9542301
TI  - [The usefulness of intrinsic risk factors of infection of the surgical site as
      predictors of other infections and death].
AB  - BACKGROUND: The use of two indices of patient intrinsic risk of surgical site
      infection, the SENIC index and the NNIS index, have been recommended to adjust
      for the case-mix and improve the comparability of infection rates across
      different hospitals. We assess the usefulness of the indices in predicting other
      infection sites and in-hospital death. METHODS: A prospective study on 1,483
      patients admitted to a service of general surgery was performed. The outcomes
      were nosocomial infection and in-hospital death. Relative risk and its 95%
      confidence interval were estimated. Unconditional logistic regression analysis
      was used to adjust for potential confounders. RESULTS: In the follow-up, 155
      surgical site infections (10.5%), 19 postoperative pneumonias (1.3%), 33 urinary
      tract infections (2.2%) and 33 in-hospital deaths (2.2%). Both the NNIS index and
      the SENIC index showed a clear trend with infection risk and death; the higher
      the index, the higher the risk. After controlling for several confounders, the
      association was still observed. To assess whether the SENIC index added
      predictive power to the NNIS index (and vice versa) a linear regression analysis
      of the SENIC index on the NNIS index. A set of residuals (difference between the
      observed and expected values according to the regression equation) were
      estimated. In the logistic regression models, residuals of the NNIS index (part
      of the NNIS index unrelated to the SENIC index, whereas the residuals of the
      SENIC index did not increase the predictive power of the NNIS index. CONCLUSIONS:
      Both the SENIC index and the NNIS index are independent predictors of several
      sites of nosocomial infection and in-hospital death. The NNIS is a better
      predictor than the SENIC index.

PMID- 9542302
TI  - [Genetic typing by PCR of isolates of C. albicans obtained in a resuscitation
      unit].
AB  - BACKGROUND: Typing by PCR (random polymorphic amplification or arbitrarily primed
      PCR) consists in a random amplification with the use of initiators of unknown
      homology with respect to the mold sequence. This study is of interest given the
      development of the technology of the amplification of nucleic acids and its
      application in the epidemiologic characterization of isolates of C. albicans.
      METHODS: Fourteen strains isolates in blood cultures of 8 patients were studied.
      All were identified as C. albicans. For amplification the sequence of AP3 and
      ERIC2 were selected. RESULTS: With one strain a band pattern very different from
      that obtained with the remaining isolates identified as C. albicans was achieved
      leading to reidentification and proving that it was C. parapsilopsis. On
      combining the results obtained with the use of both initiators 7 different
      genotypes were obtained with the remaining strains: A1, 2B, 3C, 4C, 5D, 6B and
      7E. CONCLUSIONS: The discriminative power of the two initiators was similar
      although the AP3 was greater obtaining one more genotype than ERIC2. The patients
      with repeated yeast isolates over time which may be considered as the same
      episode of bacteremia, each presented the same band pattern and each was infected
      by one single clone. We herewith confirm the usefulness of typing by PCR with one
      initiator by reaction. The results may be improved with the combination of the
      profiles obtained with the use of several sequences if greater discrimination is
      required. Likewise, its use has shown to be satisfactory in both the
      identification of clones within one species and the identification of species
      within the genus.

PMID- 9542303
TI  - [Meningitis by enterovirus in pediatrics. Clinical characteristics and virologic
      diagnosis].
AB  - BACKGROUND AND METHODS: With the aim of knowing the etiology of aseptic
      meningitis (pleocytosis in LCR with negative bacterial culture and positive or
      negative virus culture or without pleocytosis with viral culture in positive
      LCR), 48 children attending the Emergency Department of our hospital from June to
      December, 1995 were prospectively studied. Pharyngeal and rectal swab, LCR for
      bacteria and virus and blood cultures were carried out. The samples were
      inoculated in fibroblasts MRC-5, RD and BGM. The cytopathic effect was identified
      by immunofluorescence. Typing was performed in the National Center of Public
      Health Care Microbiology, Virology and Immunology in Majadahonda (Spain).
      RESULTS: Isolation of the virus was positive in 40/48 (83.3%) of the children: in
      17 (35.5%) of LCR and the remaining 23/40 (47.9%) of pharyngeal and/or rectal
      swab. In all the cases the cytopathic effect was detected in MRC-5. The viruses
      found were echovirus 30 and 5. A greater incidence of the disease was observed in
      November and December. CONCLUSIONS: Meningitis by enterovirus is frequent in our
      area. Culture of the virus in LCR, the pharynx and stools is useful on suspicion
      of aseptic meningitis since the virus may be isolated from LCR in more than one
      third of the patients. Serotyping aids in surveilling the appearance of outbreaks
      and to know the predominant viruses. Cell culture is the diagnostic treatment of
      choice, but has a low sensitivity and is slow. The application of other
      techniques such as PCR which have a greater sensitivity and with high specificity
      for the diagnosis of these infections is necessary.

PMID- 9542304
TI  - [Abscess of the psoas muscle: analysis of 11 cases and review of the literature].
AB  - BACKGROUND: Abscess of the psoas muscle (AP) is an infrequent disease of
      difficult diagnosis, developing spontaneously (primary AP) or by extension of a
      subjacent infection (secondary AP). In recent years changes have been observed in
      its etiology, advances in its diagnosis and modifications in the treatment
      schedules. METHODS: The cases of AP diagnosed from 1983-1996 were retrospectively
      studied. RESULTS: The cases included 11 AP, 5 (45%) primary and 6 (55%)
      secondary, of which the source of origin were: spondylitis in four, sacroiliac
      arthritis in one and intestinal in another. The clinical presentation was
      characterized by its prolonged course (evolution of symptoms greater than 30 days
      in 64% of the cases), with the most frequent symptoms being flank/abdominal pain
      (82%) and hip/inguinal pain (45%), with fever being presented in only 36%. The
      diagnostic profitability of echography and computerized tomography (CT) were 57%
      (4/7) and 91% (10/11), respectively. One case was diagnosed with magnetic
      resonance. The causal microorganisms were: Mycobacterium tuberculosis (36% of the
      cases), Staphylococcus aureus (18%), polymicrobian flora (18%) and Salmonella
      enteritidis, Streptococcus intermedius and Escherichia coli in 9% each. Eight
      cases (73%) underwent percutaneous (5 cases) and surgical (3 cases) drainage,
      with the evolution being favorable in 10 (91%) and death in one despite adequate
      medicosurgical treatment. CONCLUSIONS: The clinical presentation of AP is often
      unspecific, thereby delaying its diagnosis, and thus, CT is the procedure of
      choice. The tuberculous etiology continues to be frequent in our environment.
      Ultrasonographic or CT guided percutaneous drainage is a valid therapeutic
      alternative versus surgery.

PMID- 9542305
TI  - [Seroprevalence of anti-human parvovirus B19 antibodies in a sample of blood
      donors in Galicia].
AB  - BACKGROUND: To determine the seroprevalence of antibodies to human parvovirus B19
      (PVB19) in a series of 92 blood donors in Galicia. METHODS: Antibodies of the
      immunoglobulin G (IgG) class were investigated in serum samples from 44 females
      and 48 males aged 18-63 years (mean: 29.40; SD: 10.81) using a commercial ELISA
      system consisting of highly specific recombinant antigen. RESULTS: Nine positive
      cases (9.78%; CI 95%: 4.76-17.98%) were detected, including six females and three
      males with a mean age slightly higher as compared to all blood donors group. The
      prevalence of antibodies against PVB19 increased with age. No sex or age
      differences in the positive results were observed. CONCLUSIONS: These data
      indicate a PVB19 seroprevalence lower that in previous studies in several
      countries and in other areas in our country; since published references are
      limited in this community, complementary studies to establish the importance of
      this virus infection are justified.

PMID- 9542306
TI  - [Human fascioliasis with atypical severe presentation. Treatment with
      triclabendazole].
AB  - BACKGROUND: Fascioliasis is a zoonosis mainly involving sheep but which
      occasionally may be found in man as an accidental host. It is acquired by the
      consumption of herbs (watercress, wild endive, and dandelion) contaminated with
      metacercarias. The adult phase is established in the biliary tree. Most of the
      human infections are asymptomatic or with unspecific self limited abdominal
      symptoms making diagnosis difficult. METHODS: A case of human fascioliasis is of
      note because of two aspects: a) the infrequent, severe life threatening form of
      presentation: recurrent subcapsular hepatic hematomas, and b) favorable evolution
      of the patient on treatment with triclabendazol (to date its use is not approved
      in humans). RESULTS: Resistance to treatment with praziquantel was observed at a
      dosis of 75 mg/day for 2 days, being repeated 15 days later with no response. The
      patient was posteriorly treated with 10 mg/kg of a single dosis of triclabendazol
      following approval as "compassive use" with a favorable clinical response.
      CONCLUSIONS: This unusual disease requires a high index of suspicion to achieve
      diagnosis. Treatment with triclabendazol should be studied as a possible
      treatment of choice given is efficacy, absence of adverse effects and comfortable
      dosage.

PMID- 9542307
TI  - [Disseminated tuberculosis with cutaneous manifestations in AIDS patients.
      Presentation of 4 cases].
AB  - BACKGROUND: Acute cutaneous miliary tuberculosis is a rare form of Mycobacterium
      tuberculosis infection which has been described in only 25 published cases in the
      last 15 years. The appearance of serious disseminated forms of tuberculosis is
      enhanced by the severe immunodeficiency which characterizes AIDS. METHODS: Four
      cases are described of disseminated tuberculosis with cutaneous localization
      clinically described as the acute miliary form. Patients had AIDS and CD4
      lymphocyte levels of < 100 cells/mm3. Diagnosis was established in all cases by
      scraping of cutaneous lesions and direct examination with Ziehl-Neelsen
      coloration. RESULTS: The 4 patients presented signs and symptoms of disseminated
      tuberculosis with cutaneous manifestations, without a definite pattern and with
      localization predominantly on the thorax. Three had BAAR-positive sputum.
      Multiresistant strains of Mycobacterium tuberculosis were confirmed by
      antibiogram. One patient infected by a strain sensitive to first-line drugs
      responded favorably to conventional treatment for disseminated tuberculosis. In
      the remaining three with multiresistant strains, the evolution of the disease was
      rapid and unfavorable. CONCLUSIONS: Abrupt appearance of cutaneous lesions in a
      patient with disseminated tuberculosis and advanced HIV-disease should raise the
      suspicion of its etiology. Scraping and direct examination using Ziehl-Neelsen
      coloration is practical, economical and non-invasive diagnostic method.

PMID- 9542308
TI  - [Otitis externa in a patient with radical mastoid cavity].

PMID- 9542309
TI  - [Ocular sensation of foreign body and generalized pruritus in a young Guinean
      woman].

PMID- 9542310
TI  - [Ciprofloxacin and acute psychosis].

PMID- 9542311
TI  - [Bacteremia by Agrobacterium radiobacter of unknown origin].

PMID- 9542312
TI  - [Corynebacterium pseudodiphtheriticum: a new respiratory pathogen? Presentation
      of one case of acute suppurative tracheobronchitis].

PMID- 9542313
TI  - [Evaluation of the detection of IgM by EIA against the p18 protein of the IgG
      capsid against EBNA in the diagnosis of acute Epstein-Barr infection].

PMID- 9542314
TI  - [Infection by Chromobacterium violaceum in a patient with acquired
      immunodeficiency virus infection].

PMID- 9542315
TI  - [Lymph node cryptococcosis as the initial manifestation of AIDS].

PMID- 9542316
TI  - [Sparfloxacin].

PMID- 9542317
TI  - Primary effusion lymphoma containing human herpesvirus 8 DNA in two AIDS patients
      with Kaposi's sarcoma.
AB  - BACKGROUND AND OBJECTIVE: Primary effusion lymphomas (PELs) containing Kaposi's
      sarcoma-associated herpesvirus (human herpesvirus 8/HHV-8) DNA sequences
      represent a distinct but heterogeneous group of rare non-Hodgkin's lymphomas of
      null-cell phenotype/B-cell origin. We aimed to describe the clinicopathologic
      features of two human immunodeficiency virus (HIV)-related PELs occurring in
      homosexual men with Kaposi's sarcoma (KS). DESIGN AND METHODS: Thoracentesis was
      followed by morphologic plus immunophenotypic studies and molecular analysis of
      tumor cell DNA by means of combination of polymerase chain reaction and Southern
      blot analysis. RESULTS: Patients developed recurrent lymphomatous effusions
      lacking tissue involvement, in the context of severe immunodepression (CD4 count
      < 60/microL) and anti-retroviral therapy. The effusions disclosed an immunoblast
      like population CD45/CD30+, but B-cell- and T-cell-associated antigen negative,
      showing clonal immunoglobulin heavy chain gene rearrangements and harbouring HHV
      8 DNA sequences. One case contained Epstein-Barr virus genome with no evidence of
      c-myc, bcl-2 and bcl-6 gene alterations. Both patients had aggressive disease.
      INTERPRETATIONS AND CONCLUSIONS: These cases represent additional examples of PEL
      associated with HHV-8 and confirm that the group of HIV-positive homosexual men
      may be at highest risk for PEL.

PMID- 9542318
TI  - Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear
      cell subsets from healthy donors and HIV-infected patients.
AB  - BACKGROUND AND OBJECTIVE: P-glycoprotein (P-gp) is a transmembrane efflux pump
      that actively extrude a variety of unrelated drugs from cancer cells, leading to
      the so-called multidrug resistance (MDR) phenomenon. However, P-gp has also been
      found in normal bone marrow and peripheral blood mononuclear cells (PBMC).
      Recently, the presence of P-glycoprotein in PBMC from human immunodeficiency
      virus (HIV)-infected patients has also been investigated and a phenotype
      associated P-gp expression has been detected. DESIGN AND METHODS: A total of
      thirty-eight HIV-1 positive patients with a mean age of 34 years (range, 24-41
      years) were studied after an informed consent. Peripheral blood mononuclear cells
      (PBMC) were isolated by centrifugation on a Ficoll/Hypaque and P-glycoprotein
      expression was investigated on lymphocyte population by single and double-color
      immunofluorescence techniques. We investigated: i) both surface and intracellular
      expression of the P-gp molecule in different PBMC subsets, ii) P-gp expression
      modifications occurring during HIV infection, and iii) the effect of HIV-gp120 on
      the expression of P-gp by T lymphocyte subsets from healthy donors. RESULTS: Our
      experimental findings indicate that: a) P-gp glycoprotein can be detected on an
      intracellular level in different PBMC subpopulations (mainly CD8+ T lymphocytes,
      CD16+ NK cells and CD14+ monocytes); b) this intracellular expression is
      decreased in specific PBMC subsets (i.e. T-CD8+ and NK-CD16+) from HIV-infected
      patients and c) a rearrangement was obtained when CD4+ and CD8+ lymphocytes from
      healthy donors were exposed in vitro to the HIV-binding glycoprotein gp120.
      INTERPRETATION AND CONCLUSIONS: Our results indicate that P-gp glycoprotein can
      also be expressed intracellularly and can be rearranged in PBMC subsets from HIV
      infected patients.

PMID- 9542319
TI  - Detection and monitoring of trisomy 8 by fluorescence in situ hybridization in
      acute myeloid leukemia: a multicentric study.
AB  - BACKGROUND AND OBJECTIVE: The role of fluorescence in situ hybridization (FISH)
      in the detection and monitoring of trisomy 8 (+8) in acute myelogenous leukemia
      (AML) has not been defined exactly. This multicentric study was performed in
      order to: i) analyze the sensitivity of interphase FISH with respect to
      conventional chromosome analysis (CCA) in detecting +8; ii) compare the results
      of FISH and CCA in the quantitation of the frequency of +8-positive cells; iii)
      analyze the possible role of FISH in the cytogenetic follow-up of patients with
      +8. DESIGN AND METHODS: One hundred and ninety-eight nonconsecutive patients with
      a diagnosis of AML seen at five centers over a 3-year period were studied by CCA
      and FISH with a chromosome 8-specific centromeric probe. Two hundred interphase
      cells were scored in each test and the cut-off for the recognition of +8 was set
      at 3%. An irrelevant pericentromeric probe was used as negative control in those
      cases with an apparently normal karyotype and trisomy 8 in interphase cells. FISH
      studies were conducted at diagnosis and, in 14 cases with +8, on 1.5 occasions
      during follow-up. RESULTS: Karyotype aberrations were seen in 121 cases (61.1%),
      with +8 being present in 38 of them (16 as the sole aberration). Interphase FISH
      detected +8 in 37/38 cases; in a patient with 1/10 metaphases with +8, 2.3%
      interphase cells with 3 signals were seen. Fourteen additional cases with occult
      +8 were detected by FISH, which showed 4-22% interphase cells with three signals;
      6 patients had an abnormal karyotype without +8, 3 had a normal karyotype, 5 had
      no analyzable mitoses. In 24 cases with > 15 analyzable metaphases, percent
      variations between CCA and FISH in the estimation of the size of the trisomic
      clone ranged between 0.4% and 51%, median value 22%. Underestimation of the
      percent of trisomy 8 by FISH occurred in all 10 cases with > 90% +8 metaphases.
      In 7/14 cases investigated sequentially, FISH detected 5-35% trisomic cells in
      the BM after induction therapy (4 CR, 3 PR); 4 cases relapsed with +8 at 8-15
      months. The absence of +8 in remission marrows was documented in the remaining 7
      cases, 4 of which relapsed at 20-32 months. INTERPRETATION AND CONCLUSIONS: It is
      concluded that FISH was a valuable method in this multicentric study since it
      showed greater sensitivity than CCA in detecting minor clones with +8, in
      patients with both normal and abnormal karyotypes. The role of FISH in the
      cytogenetic follow-up of trisomies in AML patients may be promising.

PMID- 9542320
TI  - Short course infusional idarubicin plus intermittent cytarabine and etoposide for
      refractory hematologic malignancies: clinical and preliminary pharmacological
      results.
AB  - BACKGROUND AND OBJECTIVE: Idarubicin (IDA) is relatively immune to the multidrug
      resistance P-gp mechanism that is frequently expressed in recurrent and
      refractory hematologic malignancies. Owing to rapid metabolism in vivo, a
      continuous infusion (CI) of IDA might prolong exposure time to the parent drug
      rather than its more P-gp susceptible alcohol metabolite. For this reason we
      developed a brief retreatment schedule incorporating CI IDA in order to obtain
      clinical as well as preliminary pharmacological data in patients with refractory
      leukemias and lymphomas. DESIGN AND METHODS: Eligible patients had either
      advanced-stage acute myeloid or lymphoid leukemias (AML, ALL) or high-grade non
      Hodgkin's lymphomas (NHL) which failed curative-intent frontline or salvage
      regimens in use at our institution during the study period (July-October 1992).
      CI IDA 5 mg/m2/d was employed together with intermittent (every 8 hours)
      intermediate-dose cytarabine (500 mg/m2) and etoposide (200 mg/m2); all drugs
      were given for 2-4 days. A preliminary pharmacokinetic evaluation of CI IDA was
      carried out in three patients, including a comparison with bolus delivery in one.
      The in vitro effects of CI-type vs bolus-type IDA delivery in terms of
      intracellular IDA accumulation and related pro-apoptotic activity were assessed
      in P-gp- and P-gp+ human leukemic CEM cells by means of cytofluorimetry (IDA
      fluorescence intensity = FI, annexin V expression), with and without the addition
      of P-gp inhibitor cyclosporin A (CsA). RESULTS: Complete (2) or partial (4)
      responses were achieved in a total of 12 patients (17% and 33%, respectively),
      despite prior treatments with anthracyclines (100% of cases) and cytarabine
      etoposide (33% of cases). Hematological toxicity caused the duration of treatment
      to be reduced from 4 days to 2 days after the first 4 patients. The procedural
      death rate was 42% (5/12), which was probably related in part to the sum of
      adverse prognostic characteristics: median patient age 55 years, two-thirds of
      cases having previously failed second/third-line regimens. The pharmacokinetic
      study showed an increased plasma AUC value with CI IDA in one patient (2.9-fold
      increase vs bolus delivery) due to the prolonged presence of low IDA plasma
      levels (10-20 ng/mL vs 50 ng/mL), as seen in two other cases as well. On the
      other hand, the in vitro study did not prove to be in favor of CI IDA because the
      FI threshold (> 1500 units) associated with increased apoptosis of P-gp+ cells (>
      10%) was achieved only with bolus-type IDA exposure (50 ng/mL for 30') plus CsA.
      INTERPRETATION AND CONCLUSIONS: This short regimen demonstrated activity against
      end-stage leukemias and lymphomas and might prove to be more effective and less
      toxic in younger patients and in those with less advanced disease. In view of the
      results from plasma pharmacokinetics and in vitro intracellular IDA accumulation
      and apoptosis assays in lymphoblastic CEM cells, CI IDA 5 mg/m2/day may not
      represent a better therapeutic option than a rapid bolus injection, particularly
      in P-gp+ neoplasms. If obtaining an adequate intracellular drug concentration is
      the primary treatment goal, a higher CI IDA dosage, the addition of a P-gp down
      regulator such as CsA and others, and in vivo study focusing on tumor samples
      from patients could all be helpful.

PMID- 9542321
TI  - Treatment of elderly patients with AML: results of an individualized approach.
AB  - BACKGROUND AND OBJECTIVE: AML treatment in elderly patients must be
      individualized according to their characteristics. We report the results of a
      tailored treatment approach in all consecutive AML patients older than 60 years
      diagnosed at our institution during the last 2 years. DESIGN AND METHODS: Between
      December 1994 and December 1996, 43 AML patients over 60 years of age (median,
      72; range 61-89) were managed according to their performance status (PS) and
      associated diseases. Twenty patients (46%) were eligible for intensive
      chemotherapy and received combination chemotherapy including an anthracycline
      (Idarubicin or daunorubicin), ara-C and VP-16. After complete remission (CR),
      consolidation chemotherapy with mitoxantrone and intermediate-high-dose ara-C was
      given to 13 of the 15 patients in remission (65% of all patients candidates for
      intensive treatment). Twenty-three patients who were not eligible for intensive
      chemotherapy received palliative measures. RESULTS: Patients treated with one
      course of intensive chemotherapy had a CR rate of 70% (95% CI: 48-92%)(n = 14)
      with a mortality rate of 20% (n = 4) and a resistance of 10% (n = 2). An
      additional patient reached CR after rescue therapy. Median CR duration was 10.5
      months. Median survival was 10.5 months. Patients above 70 years had a median
      survival of 5 months compared to the median not reached for those aged between 60
      and 70 years (p = 0.03). This latter group had a probability of survival of 52 +/
      18% at 18 months. None of the patients treated with palliative measures achieved
      CR and the median survival in this group was only 1.5 months. INTERPRETATION AND
      CONCLUSIONS: Patients with AML aged 70 years or less with good PS and without
      severe associated diseases should be intensively treated due to the high
      probability of achieving CR and an acceptable median-term survival. By contrast,
      results in patients 70 years or older and in those suitable only for palliative
      treatment because of a poor PS or severe associated diseases are very poor.
      Alternative treatment approaches for these patients should be investigated.

PMID- 9542322
TI  - Two dosage interferon-alpha 2b maintenance therapy in patients affected by low
      risk multiple myeloma in plateau phase: a randomized trial.
AB  - BACKGROUND AND OBJECTIVE: The role of interferon (IFN) in the remission phase of
      multiple myeloma (MM) is still an open question, particularly for its scheduling
      and the subset of patients who could benefit from this approach. The present
      randomized multicenter study was designed to compare two schedules of IFN
      maintenance therapy in order to assess the difference in effectiveness and
      tolerance. DESIGN AND METHODS: This prospective randomized multicenter study was
      attempted to assess the best schedule of IFN administration in the maintenance
      treatment of MM in plateau phase with regard to progression free survival (PFS)
      and toxicity. The second aim was defining the difference between the two
      schedules in overall survival (OS) and identifying the critical dose of IFN
      therapy needed to prolong plateau phase and survival. We enrolled 52 patients
      affected with low-risk MM (i.e. with serum beta 2-microglobulin < 6.0 mg/L and
      serum albumin > 3.0 g/dL); 27 patients (group A) were randomly assigned to
      receive IFN alpha-2b 3 megaunits (MU) subcutaneously three times a week and 25
      patients (group B) 3 MU/day until disease progression. RESULTS: Median
      progression free survival (PFS) was 11.9 months in group A and 38.3 months in
      group B (p = 0.0038). Median survival was 63.2 months in group A and 61.9 months
      in group B (p = 0.489). However, those patients who were given an IFN dose > or =
      30 MU/month experienced a significantly longer PFS and survival than the other
      patients. Seventeen patients (32.7%) discontinued therapy and sixteen patients
      (30.8%) reduced IFN alpha-2b dose because of severe side effects without having a
      significant difference between the two schedules. INTERPRETATION AND CONCLUSIONS:
      Our results show that patients treated with IFN alpha 3 MU/day had a
      significantly longer remission duration than patients treated with IFN alpha 3 MU
      three times weekly. Moreover, an IFN dose is probably critical for obtaining a
      longer survival in patients affected with low-risk MM. Since the patients'
      discomfort during a IFN maintenance therapy was frequently experienced the
      quality of their lives should be carefully taken into account.

PMID- 9542323
TI  - Allogeneic peripheral blood stem cell transplantation in patients with early
      phase hematologic malignancy: a retrospective comparison of short-term outcome
      with bone marrow transplantation.
AB  - BACKGROUND AND OBJECTIVE: Transplantation of mobilized allogeneic peripheral
      blood stem cells (PBSC) has recently been reported by several groups. However,
      few patients receiving an allograft in the early stage of their disease have been
      described so far. DESIGN AND METHODS: Fifteen patients with early stage
      hematologic malignancies were transplanted with cryopreserved allogeneic PBSC
      from HLA-identical siblings. PBSC were collected after priming with 10
      micrograms/kg/day of glycosylated granulocyte colony-stimulating factor (G-CSF,
      lenograstim). Outcomes were compared to a historical control group of 15 patients
      who received conventional bone marrow transplantation (BMT) from HLA-identical
      sibling donors. The two groups were matched for diagnosis, stage of disease, age,
      preparative regimen, graft-versus host (GVHD) prophylaxis, patients' and donors'
      gender and cytomegalovirus (CMV) serology. Diagnoses in both groups were: chronic
      myelogenous leukemia (CML) in first chronic phase (= 5), acute leukemia in first
      complete remission (CR) (= 5), non-Hodgkin's lymphoma in CR (= 1) and multiple
      myeloma (MM) with sensitive disease (= 4). All patients were given cyclosporin-A
      (CsA) and methotrexate (MTX) for GVHD prophylaxis. Preparative regimens varied
      according to diagnosis and included either busulfan/cyclophosphamide combination
      (BU/Cy) or total body irradiation/cyclophosphamide +/- melphalan (TBI/Cy +/-
      Mel). RESULTS: The patients in the PBSC group showed a more rapid hematopoietic
      reconstitution with a significant difference in the median times to 1 x 10(9)
      neutrophils/L (19 days vs. 26 days; p = 0.03) and to platelet transfusion
      independence (18 days versus 22 days; p = 0.02). This finding was associated with
      a significantly shorter hospitalization (28 days versus 33 days after
      transplantation; p = 0.01). In the PBSC series, grade II-IV acute GVHD occurred
      in 3 patients (20%) and grade III-IV in 1 patient (7%). In the BMT control group,
      grade II-IV aGVHD was reported in 2 cases (13%; p = NS) and 1 case had grade III
      IV GVHD. Chronic GVHD developed in 7 patients (47%) (limited = 6; extensive = 1)
      undergoing PBSC transplantation and 5 patients (33%) (limited = 4; extensive = 1)
      in the BMT series (p = NS). No difference was found in the incidence of grade II
      IV (according to the World Health Organization) mucositis, whereas PBSC
      recipients did have a significantly lower incidence of additional severe (grade
      III-IV) organ toxicity. After a median follow-up of 300 days (range 180-630), all
      PBSC patients are still alive with a median Karnofsky score of 100% (range 80%
      100%). Thirteen patients are in CR and 2 myeloma patient are in good partial
      remission (PR). Also, in the BMT group the peritransplant mortality was absent;
      two MM patients died due to progressive disease at day +796 and +1,023,
      respectively; one leukemic patient died of chronic GVHD 407 days after
      transplantation and one additional leukemic individual relapsed 1,140 days after
      BMT. INTERPRETATION AND CONCLUSIONS: This retrospective comparison suggests that
      allogeneic PBSC transplantation performed in the early stage of the disease is
      safe and may be associated with a more rapid hematopoietic reconstitution than
      BMT, as well as lower transplant-related toxicity and earlier hospital discharge
      with apparently no increased risk of acute and chronic GVHD.

PMID- 9542324
TI  - The molecular biology and pyridoxine responsiveness of X-linked sideroblastic
      anaemia.
AB  - Pyridoxine-responsive, X-linked sideroblastic anaemia (XLSA) has been shown to be
      caused by missense mutations in the erythroid-specific ALA synthase gene, ALAS2.
      These are scattered widely across the part of the gene encoding the catalytic
      domain and in half the cases affect residues conserved throughout evolution. Only
      a loose correlation has been found between the in vitro kinetics and stability of
      the catalytic activity of the recombinant variant enzymes and the in vivo
      severity and pyridoxine-responsiveness of the anaemia. Enhanced instability in
      the absence of pyridoxal phosphate (PLP) or decreased PLP and substrate binding
      have been noted. A detailed explanation of the anaemia and its response to
      pyridoxine, however, requires greater insight into the structure-function
      relationships of this protein than we have at present. Knowledge of its tertiary
      structure and further knowledge of intracellular factors which impinge on the
      ability of normal and variant ALAS2 to contribute to haemoglobin production are
      also required. Mutations in the same gene which affect mitochondrial processing,
      terminate translation prematurely, or are thought to abolish function altogether
      cause an XLSA that is refractory to treatment with pyridoxine. A major
      complication of this disorder is its accompanying increased iron absorption and
      iron overload which occurs in patients and female heterozygotes. Mutation
      detection enables the early diagnosis of those affected, targeted education of
      families, early treatment with pyridoxine and prevention of iron overload. It
      also allows for a distinction to be made between late-onset variants of this
      condition and the more insidious refractory anaemia with ring sideroblasts. The
      next few years of investigation should be illuminating as tools now exist to
      study all aspects of this protein from the gene to the mitochondrial matrix.

PMID- 9542325
TI  - Pathogenesis, etiology and epidemiology of myelodysplastic syndromes.
AB  - BACKGROUND AND OBJECTIVE: The myelodysplastic syndromes are common hematological
      malignancies affecting predominantly elderly people. Patients usually present
      with chronic cytopenias which gradually worsen due to progressive bone marrow
      failure or transformation into acute myeloid leukemia. Disease prevention is more
      cost-effective than therapeutic intervention and the establishment of the
      etiology and pathogenesis of MDS therefore assumes considerable importance. This
      review will outline current concepts of the pathobiology of MDS, putative
      etiological insults and the mechanisms of disease initiation as well as recent
      contributions to the descriptive epidemiology of these disorders. EVIDENCE AND
      INFORMATION SOURCES: The authors of the present review have a long-standing
      interest in the pathogenesis, etiology and epidemiology of MDS. Journal articles
      covered by the Science Citation Index and Medline have been reviewed and personal
      experience and discussion with international experts collated. STATE OF THE ART
      AND PERSPECTIVES: The initiation processes for the development of MDS remain
      unknown. A poorly defined transforming event affects a pluripotent or multipotent
      progenitor cell in the bone marrow, conferring a growth advantage upon it and
      eventually establishing clonal hematopoiesis. An important pathogenetic mechanism
      in MDS is premature intramedullary cell death via excessive apoptosis, explaining
      the apparent paradox of a cellular marrow in combination with peripheral
      cytopenias (ineffective hematopoiesis). Therapy-related MDS/AML following
      exposure to alkylating agents is the only clear etiological factor thus
      identified. Increasing evidence for exposure to benzene and radiation and the
      development of MDS is emerging. Benzene hematotoxicity is mediated via both
      genotoxic and non-genotoxic mechanisms, leading to aplasia, apoptosis and
      initiation (via genetic mutation) of clonal disorders such as MDS. Further
      studies of benzene hematotoxicity and therapy-related MDS should provide models
      for the elucidation of initiation events in MDS pathogenesis. The importance of
      such studies is emphasized by the rising frequency of MDS which largely reflects
      improved diagnostic criteria, increased physician awareness and extended use of
      diagnostic procedures in the elderly. Demographic changes will lead to a marked
      increase in MDS over the next few decades.

PMID- 9542326
TI  - Plasmablastic lymphoma of the stomach. A case report.
AB  - We report the case of a 53 year-old woman with a gastric tumor showing
      morphological, phenotypical and molecular features of a plasmablastic lymphoma, a
      recently recognized subtype of diffuse large B-cell lymphoma. The tumor was
      composed of plasmablast-like cells, lacked CD45 and B-cell associated antigens,
      expressed the plasma cell-associated antigen CD38, and showed clonally rearranged
      IgH genes in the absence of bcl-2 and bcl-6 genes rearrangement.

PMID- 9542327
TI  - A case of microcytic anemia.

PMID- 9542328
TI  - Waldenstrom's macroglobulinemia complicated with acute myeloid leukemia. Report
      of a case and review of the literature.
AB  - The evolution of Waldenstrom's macroglobulinemia (WM) into chronic or acute
      myeloid leukemia (AML) is a rare event. Most of these cases have occurred after
      treatment with alkylating agents. We herein report a case of WM terminating in an
      acute myelomonocytic leukemia after treatment with prednimustine and chlorambucil
      and present a review of the literature.

PMID- 9542329
TI  - Idiopathic thrombocytopenic purpura associated with Crohn's disease.
AB  - Besides cytopenia related to treatment, several hematological disorders such as
      anemia, abnormal platelet activity, thrombosis, presence of anticardiolipin or
      anti-neutrophil antibodies, cyclic neutropenia, and myelodysplasia, have been
      reported in patients with Crohn's disease (CD). The case we report here is the
      first one documenting the association of idiopathic thrombocytopenic purpura
      (ITP) with CD.

PMID- 9542330
TI  - More on the appropriate fluorochrome-conjugated CD34 antibody choice for the flow
      cytometric detection of circulating progenitor cells.

PMID- 9542331
TI  - [Kinetics of development of human melanoma xenografts in immunosuppressed
      animals].
AB  - An experimental model of development of the human tumor xenografts (melanomas
      HCMB and Bro) in immunosuppressed phenotypically normal animals (CBA/Ca mice) was
      developed. Optimal conditions were established for immunodeficiency induction in
      the animals. Kinetics of development of the xenografts in the immunosuppressed
      animals was studied. The level of 0(6)-alkyl-guanine-DNA-alkyltransferase, an
      enzyme responsible for repair of DNA damage in the tumor cells induced by
      chemotherapeutic agents (nitroalkylurea), was determined.

PMID- 9542332
TI  - [Cytochrome p-450-dependent monooxygenase in fish tissues].
AB  - Data about enzymes involved in metabolism and detoxification of xenobiotics in
      fish are summarized. Special attention is given to the comparison of
      monooxygenase systems of fish and mammals. 3-Methylcholanthrone, benzo-pyrene,
      benzo-naphthoflavone, and various technogenic pollutants present in water are
      examined as inducers of fish monooxygenase systems. The induction of cytochrome P
      450 isozymes is specially reviewed, and we discuss their difference from similar
      isozymes of other vertebrates classes. We also discuss the relationship between
      the activity of the monooxygenase system in fish and temperature conditions of
      water bodies, as well as sex-related differences in the activity of this system.
      Perspective in the use of the monooxygenase system for biological monitoring are
      reviewed.

PMID- 9542333
TI  - [Taxonomy of the musk deer (Artiodactyla, Mammalia)].
AB  - We studied the chromosome sets and specific morphological features and phenetic
      traits of hair cover coloration, as well the pattern of its inheritance upon
      experimental hybridization. The diploid set of chromosomes in the animals from
      the northern part of the range contains 2n = 58 (there are two additional B
      chromosomes in the Far Eastern musk deer) and is identical to that from the
      southern musk deer forms. Discrete polymorphic features of neck and hair cover
      coloration have been identified in the northern and southern musk deer, and these
      are used as taxonomic features. A map illustrates distribution of the established
      subspecies.

PMID- 9542334
TI  - [Comparative analysis of the acoustic characteristics of speech models of human
      prototypes and budgerigar (Melopsittacus undulatus) imitations].
AB  - Phonemic comparative analysis of vowel (i) of the Russian language was carried
      out in pronunciation of nine budgerigars and humans (three men, five women, and
      three children under eleven years old). A complex device "KAPROS-01" was used as
      an analyzer. The contact signals of the same individuals was also analyzed.
      Transposition of the main tone and formants in the frequency range by 2 kHz
      upwards and adjacency of the main tone harmonics to the first formant area are
      the main distinctions of the three-dimensional (3D) graph between bird and human.
      The bird's signal does not differ practically from the human signal according to
      the number of formants (two to three). The length of vowel (i) in budgerigars
      averages 19% of the total word length, versus 29% in humans. The main voice
      frequency in budgerigars in their contact signals varies from 2.2 to 3.4 kHz and,
      in imitations, from 2.3 to 3.0 kHz.

PMID- 9542335
TI  - [Changes in the serum albumin system during toxic syndrome and their
      pharmacologic correction].
AB  - In connection with the important role of serum albumins in pathogenesis and
      sanogenesis of numerous toxic states, we examined binding capacity of these
      proteins and conditions of their binding sites after acute poisoning with
      tetrachloromethane (TCM) and administration of antihypoxic agents (sodium gamma
      hydroxybutirate), antioxidants (Dibunol), and actoprotector (Tomersol) to rats.
      We demonstrated that tetrachloromethane intoxication (3.2 g/kg over 24 h) was
      accompanied by a certain decrease (by 13.8%) in the total blood serum level of
      albumins and a tendency to a decrease in the value of the binding constant of
      negatively charged fluorescent probe 1-(phenylamino)-8-sulfonaphthalene. Under
      these conditions, the mean number of probe binding sites per albumin molecule
      increases, and as a result, the total concentration of albumin binding sites in
      the serum remains virtually unchanged. We found that accessibility of the probe
      to a quenching agent (potassium nitrate) increases in the protein--probe complex
      under intoxication conditions, suggesting that the type of interaction between
      the protein and the fluorescent probe changes as well. Therapeutic/prophylactic
      administration of an antioxidant, antihypoxic agent, or actoprotector leads to an
      increase in the level of albumin in the serum (Tomersol), partial normalization
      of its binding properties (binding constant in the case of sodium gamma
      oxybutirate, mean number of binding sites per molecule for Dibunol and Tomersol),
      and the state of binding sites (sodium gamma-oxybutirate, Dibunol).

PMID- 9542336
TI  - [Various aspects of the effect of heparin-serotonin complex on blood and blood
      flow].
AB  - High-molecular heparin-serotonin complex (3:1 weight ratio) was obtained in
      vitro. The complex, its components, and heparin-serotonin mixture were introduced
      intraperitoneally in rats, and the resulting effects were registered 10, 30, and
      60 min later. The complex had anticoagulant and lytic activities distinct from
      those of plasmin. According to decrease activity of factor XIII and decreased
      concentration of fibrinogen, the complex stimulated the anticoagulant system. In
      addition, the heparin-serotonin complex penetrated the hematoencephalic barrier
      and decreased the rate of brain bloodstream. The observed physiological
      properties of the heparin-serotonin complex were distinct from those of
      serotonin, heparin, and their mixture.

PMID- 9542338
TI  - Trends in funding for medical entomological research.

PMID- 9542337
TI  - [Receptor binding of aldosterone in the brain of rats with different types of
      behavior under normal conditions and after stress].
AB  - Results are given from experiments on binding of [3H]aldosterone to the
      cytoplasmic corticosteroid receptors, in the brain structures of the rat with
      different types of behavior under normal conditions 10 min and two weeks after
      its peritoneal injection. Binding of [3H]aldosterone to cytoplasmic
      corticosteroid receptors of the hippocampus, rather than the brain (without
      hippocampus and cerebellum), was shown to depend on the type of animal behavior.
      Stress was also shown to affect binding of this hormone to cytoplasmic
      corticosteroid receptors of the brain (without hippocampus and cerebellum),
      rather than hippocampus.

PMID- 9542339
TI  - Fleas in French Guiana (Insecta: Siphonaptera).
AB  - Based on a collection of approximately 760 fleas, of which 520 were collected in
      1994-1995 during scientific studies at the Petit Saut dam site in French Guiana,
      12 species and subspecies are discussed. Two taxa, Rhopalopsyllus garbei
      Guimaraes, 1940 and Adoratopsylla intermedia copha (Jordan, 1926), are new
      records for French Guiana. The fleas collected during the 1994-1995 study were
      obtained from 35 species of mammals (3,484 specimens); of which, 21 (60%) species
      were negative for fleas. The mammals were captured primarily by live-trapping
      during a capture-release study along a portion of the Sinnamary River and its
      tributaries up to a distance of 70 km upstream from the Petit Saut dam site.

PMID- 9542340
TI  - Patterns of activity in host-seeking adult Ixodes scapularis (Acari: Ixodidae)
      and host-produced kairomones.
AB  - Adult blacklegged ticks, Ixodes scapularis Say, were confined to clay islands
      each surmounted with a vertical glass rod, and tick activities were videotaped
      continuously for 48 h. Some rods were treated basally or apically with substances
      rubbed from pelage associated with the tarsal or interdigital glands of white
      tailed deer, Odocoileus virginianus (Zimmermann). Except for the activity
      immediately following their release, tick activity on both days was greatest
      during the period from 1700 to 2300 hours, which coincided with the onset of
      scotophase. Ticks were most active when rods had interdigital gland substances
      applied to their basal 2 cm, whereas they were least active when confined with
      rods treated with tarsal gland substances on their apical 2 cm. Overall, ticks
      spent more time on the apical 2 cm of the glass rods during the scotophase than
      during the photophase. The highest level of apical arrestment among treated and
      untreated rods occurred when the rod tips were treated with tarsal gland
      substances, with female ticks on the apical 2 cm of the rods 70-100% of every 3-h
      period beginning with the period from 2000 to 2300 hours on day 1. In contrast,
      when tarsal gland substances were applied to the basal 2 cm of the rods, the
      ticks spent < 40% of every period on day 2 on the rod tips.

PMID- 9542341
TI  - Morphometric multivariate analysis of field samples of adult Anopheles arabiensis
      and An. gambiae s.s. (Diptera: Culicidae).
AB  - The Afrotropical complex of sibling species Anopheles gambiae Giles includes the
      most efficient vectors of human malaria south of the Sahara. Anopheles arabiensis
      Patton and An. gambiae s.s. Giles are the members of the complex more adapted to
      the human environment. They are sympatric and synchronic over most of their
      distribution range; however, they show a different involvement in malaria
      transmission, with An. gambiae being more anthropophilic and endophilic than An.
      arabiensis. Discriminating between them is essential for a correct assessment of
      epidemiological parameters. The identification is currently achieved through
      recognition of species-specific chromosomal inversions or by molecular biology
      techniques. Both methods require considerable technical resources, not always
      available in the field. We carried out a morphometric analysis of field and
      laboratory samples of An. arabiensis and An. gambiae s.s. from sites in
      Madagascar, Burkina Faso, Mali, and Liberia to evaluate the degree of
      morphological differentiation. We examined 17 morphometric characters in samples
      representing each of the geographic sites. All of the measures were significantly
      larger for An. arabiensis (regardless of the collection site), demonstrating an
      intrinsic greater body size of this species. To assess the reliability associated
      with the multivariate statistic, we applied the discriminant function analysis,
      which provided a method for predicting to which group a new case will most likely
      be assigned. In a blind experiment, the morphometric method correctly identified
      approximately 85% of field-collected An. arabiensis and An. gambiae s.s., which
      provided a relatively simple method to approximate the relative frequencies of
      the 2 species in areas in which their concurrent presence was already known. The
      influence of laboratory conditions on the morphometrics of the 2 species was also
      analyzed.

PMID- 9542342
TI  - Seasonal oviposition and temperature requirements of eggs may limit northern
      distribution of European Argas reflexus (Acari: Argasidae).
AB  - Seasonal reproduction and embryonic development was investigated in Argas
      reflexus (F.) throughout a 5-yr period. Ticks were kept in desiccators at
      approximately 76% RH at 2 experimental sites--an attic and an outdoor aviary-
      that provided a natural photoperiod and temperature. Tick oviposition was limited
      to the summer months (June through August) regardless of the year of
      investigation and of the seasonal time of tick feeding. Engorged female ticks
      entered diapause between late July and late August. Ticks that had already
      started oviposition, stopped at that time and continued in the following year
      without requiring another blood meal. In the laboratory, A. reflexus eggs
      exhibited an upper lethal temperature (ULT50: 1-h exposure) of 44.1 degrees C
      (95% CL: 43.7-45.5 degrees C), which is in accordance with the increased egg
      mortality observed in the attic, where temperatures reached > or = 45 degrees C.
      A. reflexus eggs showed a low level of cold tolerance. Despite a supercooling
      point of approximately -25 degrees C, their lower lethal temperature (LLT50: 24-h
      exposure) was only -12.3 degrees C. Even at a typical winter temperature of 3
      degrees C and 76% RH, 50% egg mortality occurred after only approximately 34 d.
      In the attic and the aviary, none of the A. reflexus eggs were able to overwinter
      successfully during any of the investigated winters, including comparatively mild
      ones. The results strongly suggest that the temperature sum available for
      embryonic development in summer/autumn limits the northern distribution of A.
      reflexus.

PMID- 9542343
TI  - Random amplification of polymorphic DNA as a tool for taxonomic studies of
      triatomine bugs (Hemiptera: Reduviidae).
AB  - Eleven of 27 decameric primers were found to be suitable for random amplification
      of polymorphic DNA (RAPD) from triatomine bugs on the basis that they produced
      discrete profiles and distinguished among Panstrongylus megistus (Burmeister),
      Rhodnius prolixus Stal, and Triatoma infestans (Klug). The legs, or single leg
      segments, of individual bugs were used as the source of DNA so that the taxonomic
      value of the bug was conserved. Within the scope of the specimens studied, RAPD
      profiles allowed assignment to species even when bugs were kept dry for up to 12
      mo. Profiles for individuals within a species were not identical. RAPD profiles,
      with the specimens tested, distinguished among species of 3 pairs considered to
      be morphologically similar and closely related, namely, Rhodnius ecuadorensis
      Lent & Leon and Rhodnius pictipes Stal; Rhodnius nasutus Stal, and Rhodnius
      neglectus Lent; Rhodnius prolixus Stal and Rhodnius robustus Larrousse. RAPD data
      conformed with the perceived affinities among these species. RAPD polymorphisms
      were seen with T. infestans from 3 different localities, but none of the
      polymorphisms was confined to 1 source. RAPD provided a molecular basis to
      reassess taxonomic relationships within the Triatomine subfamily. The accurate
      distinction of triatomine species and of intraspecific bug populations may
      contribute to elimination of vector-borne Chagas disease from the Americas.

PMID- 9542344
TI  - Population dynamics of the house dust mites Dermatophagoides farinae, D.
      pteronyssinus, and Euroglyphus maynei (Acari: Pyroglyphidae) at specific relative
      humidities.
AB  - Experiments were conducted to determine the effects of relative humidity on the
      population dynamics of single and mixed species of Dermatophagoides farinae
      Hughes, D. pteronyssinus (Trouessart), and Euroglyphus maynei (Cooreman) at
      specific relative humidities maintained at 20 degrees C, with unlimited food. The
      population density of single and mixed species (D. farinae and D. pteronyssinus)
      increased exponentially when cultured at 65, 70, and 75% RH. The mean population
      growth rates were 17.3 +/- 4.4 SD and 32.5% +/- 4.7/wk for D. farinae and D.
      pteronyssinus, respectively. Mean population doubling times were 2.2 +/- 0.3 and
      4.2 +/- 1.3 wk for D. pteronyssinus and D. farinae, respectively. Mixed species
      cultures, started with equal numbers of D. farinae and D. pteronyssinus, resulted
      in higher percentages of D. farinae than D. pteronyssinus. In cultures started
      with 75% of one species and 25% of the other, the more numerous species remained
      dominant and in similar ratios throughout the experiment. Both D. farinae and D.
      pteronyssinus population densities maintained at 85% RH declined over a 12-wk
      culture period because of mold growth. E. maynei were unable to survive at 65,
      70, 75, and 85% RH, which indicated that their climatic requirements were
      different from those of D. farinae and D. pteronyssinus. Population densities of
      D. farinae and D. pteronyssinus cultures declined when held at 21-22 degrees C
      and relative humidities of < or = 50%; however, at 50% RH, significant
      proportions of the populations survived for 10 wk. Half-life for desiccation of
      D. farinae and D. pteronyssinus at 45% RH was 11.5 and 1.2 wk, respectively, but
      at 50% RH was 86.3 and 4.0 wk, respectively. The data indicated that a < or = 50%
      RH would have to be maintained for long periods to reduce both D. farinae and D.
      pteronyssinus by desiccation procedures. The results of this study show that D.
      farinae and D. pteronyssinus have high reproductive potentials and population
      growth rates, which indicate that mite reduction procedures must be thorough or
      mite densities will return to high levels quickly following remediation if
      adequate food and suitable microclimatic conditions exist.

PMID- 9542345
TI  - Occurrence of Ixodes scapularis (Acari: Ixodidae) on a selected segment of the
      Appalachian Trail.
AB  - A 918-km section of the Appalachian National Scenic Trail from the West Virginia
      Maryland border to the Massachusetts-Vermont border was surveyed for the presence
      of Ixodes scapularis Say. The trail and its edges were drag-sampled during 4
      hikes between May and October 1991. Trips were designed to survey areas of the
      Appalachian Trail when I. scapularis might be questing and to revisit states
      endemic for Lyme disease during differing times. After sampling for ticks,
      meteorological and ecological characteristics were measured at each site. In
      total, 1,776 km of the Appalachian Trail were hiked during 88 d and resulted in
      sampling 489 sites. All life stages of Ixodes scapularis (n = 46) were collected
      from 21 sites within a 331-km range of the Appalachian Trail between Salisbury,
      CT, to Delaware Water Gap, PA. This segment of Appalachian Trial is easily
      accessible to a large urban population and should be posted with tick warning
      signs to alert the public to the presence of I. scapularis.

PMID- 9542346
TI  - Attachment-site patterns of adult blacklegged ticks (Acari: Ixodidae) on white
      tailed deer and horses.
AB  - The attachment site pattern of adult Ixodes scapularis Say on white-tailed deer
      and horses in Maryland was determined by whole-body examinations during fall and
      spring periods of tick host-seeking activity. On deer in the fall, both female
      and male I. scapularis attached largely to anterior dorsal body regions, with
      attachment to the ears (outside), head, neck, and brisket accounting for 87.9% of
      females and 86.6% of males. The attachment pattern of females differed between
      bucks and does during fall, but not in spring, and both females and males were
      more abundant on bucks than does during fall, but not in spring. Neither female
      nor male attachment patterns on deer differed between fall and spring seasons. In
      contrast to deer, the ears and neck of horses were largely devoid of blacklegged
      ticks, and 84% of the females were attached either on the chest, in the axillae
      of the fore and rear legs, or under the jawbone. The restricted attachment of
      female blacklegged ticks to ventral body regions of horses may reflect avoidance
      of light. An understanding of the attachment patterns of adult I. scapularis, an
      increasingly abundant and economically important species, enhances sampling of
      feeding ticks, deticking to limit host irritation or exposure to tick-borne
      pathogens, and identifies body areas that should be targeted for delivery of
      repellents or acaricides.

PMID- 9542347
TI  - Comparison of Ixodes scapularis (Acari: Ixodidae) populations and their habitats
      in established and emerging Lyme disease areas in New Jersey.
AB  - Hunterdon Country, New Jersey, experienced a significant increase in the number
      of Lyme disease cases during 1990-1995, accounting for 21.2% of all New Jersey
      cases. This study compares the relative abundance of Ixodes scapularis Say in
      similar habitats in Hunterdon County, an emerging Lyme disease area, and Monmouth
      County, where Lyme disease has been established for well over a decade. The
      extent to which differences in habitat physiognomy could explain differences in
      tick populations, and consequently Lyme disease case rates, is addressed. Ticks
      were surveyed and vegetation measurements made in 4 habitat types at 1 site in
      each county. I. scapularis was 7 times more abundant in Monmouth County than in
      the Hunterdon County site, and the distribution of all life stages among habitats
      differed significantly between sites. The greater numbers of subadult ticks at
      the Monmouth County site was attributed to greater shrub cover and litter depth
      which created more favorable microclimatic conditions for tick survival. However,
      the overall physiognomy of the different vegetation types at the sites studied in
      Monmouth and Hunterdon counties was remarkably similar and did not appear to
      explain differences in tick abundance. Until further research clarifies
      microscale differences between habitats, the differences in the case rates
      between the counties appear to be more likely the result of reporting artifact.

PMID- 9542348
TI  - Ultrastructural studies on the reproductive system of male Aedes aegypti
      (Diptera: Culicidae) infected with dengue 2 virus.
AB  - Dengue 2 virus was found by transmission electron microscopy to be present in the
      reproductive tissues of male Aedes aegypti (L) 14 d after intrathoracic
      inoculation. Dengue 2 particles were detected in the matrix, epithelial cells,
      and the peripheral fat body of the testes; secretory droplets of columnar cells
      of the accessory glands; and the epithelial and muscle cells of the seminal
      vesicles. However, none was found in the germ cells (i.e., spermatogonia,
      spermatocytes, spermatid, or spermatozoa). These observations indicate that fluid
      transfer may be the mechanism of venereal transmission of dengue 2 virus by Ae.
      aegypti.

PMID- 9542349
TI  - Competence of pheasants as reservoirs for Lyme disease spirochetes.
AB  - Pheasants, Phasianus colchicus L., constitute a major part of the ground-feeding
      avifauna of England and Wales and are important hosts to immature stages of
      Ixodes ricinus L., the principal tick vector of Lyme borreliosis spirochetes in
      Europe. Therefore, their competence as hosts for Borrelia burgdorferi Johnson,
      Schmid, Steigerwalt & Brenner sensu lato was investigated. One group of pheasants
      was inoculated by needle with 1 x 10(6) cultured B. burgdorferi s.s. organisms,
      and a 2nd group of birds was infested with I. ricinus nymphs collected from a
      focus of Lyme borreliosis in southern England. Both bird groups were subjected to
      xenodiagnoses using uninfected I. ricinus nymphs. All recovered engorged ticks,
      as well as pheasant skin biopsies, were analyzed by a nested polymerase chain
      reaction targeting the 5S-23S rRNA genes of B. burgdorferi s.l. Both groups
      proved to be infective for ticks. The birds that were infected by tick bites
      proved to be significantly more infective for ticks (23% of the xenodiagnostic
      ticks positive) than those infected by needle (5%). The results show that
      pheasants can be infected experimentally with B. burgdorferi s.l., that they can
      pass the spirochetes to ticks and that their infectivity for ticks may persist as
      long as 3 mo. We conclude that pheasants are reservoir competent for Lyme
      borreliosis spirochetes and potentially play an important role in the maintenance
      of B. burgdorferi s.l. in England and Wales.

PMID- 9542350
TI  - Genetic structure of local populations of Lutzomyia longipalpis (Diptera:
      Psychodidae) in central Colombia.
AB  - Lutzomyia longipalpis (Lutz & Neiva), the sand fly vector of American visceral
      leishmaniasis in the New World tropics, has a broad but discontinuous
      geographical distribution from southern Mexico to Argentina. A baseline for
      population genetic structure and genetic variability for this species was
      obtained by analyzing 5 local, peridomestic populations at the approximate center
      of its distribution, the Magdalena River Valley of central Colombia. Three
      populations of L. longipalpis from El Callejon, a small rural community, were
      compared with 2 populations from neighboring areas 12 and 25 km distant for
      genetic variation at 15 isoenzyme loci. The mean heterozygosity ranged from 11 to
      16%, with 1.2 to 2.3 alleles detected per locus. Nei's genetic distances among
      the populations were very low, ranging from 0.001 to 0.007. Gene flow estimates
      based on FST indicated high levels of gene flow among local L. longipalpis
      populations, with minimal population substructuring.

PMID- 9542351
TI  - Kairomonal activity of white-tailed deer metatarsal gland substances: a more
      sensitive behavioral bioassay using Ixodes scapularis (Acari: Ixodidae).
AB  - A behavioral bioassay is described that detected kairomonal activity in
      substances associated with the metatarsal glands of white-tailed deer, Odocoileus
      virginianus (Zimmermann). Dry and aqueous wipes or rubs of glandular areas
      elicited an arrestant response in adult blacklegged ticks, Ixodes scapularis Say.

PMID- 9542352
TI  - Bone grafting in foot and ankle surgery. A review of 300 cases.
AB  - Three hundred foot and ankle bone grafts were reviewed in three separate series
      of 100 consecutive grafts from two institutions. The series represent a period
      from 1977 to 1990 and demonstrate treatment patterns that varied over time and
      between institutions in indications, graft material, and perioperative
      management. Over 42% of the 300 grafts were for calcaneal osteotomies; most were
      Evans calcaneal osteotomies. Over 72% of the grafts were allogeneic bone-bank
      bone, which performed well in calcaneal osteotomies and for packing of defects.
      Upon review of the incidence of bone complications, no significant differences
      were observed between surgical procedures that used autogenous versus allogeneic
      grafts. However, four out of six failures of first metatarsal repair were with
      allogeneic bone. There was a significant difference in complication rates for the
      major indications for bone-graft surgery. Nonunions and arthrodeses resulted in
      higher complication rates than expected, whereas calcaneal osteotomies resulted
      in a lower complication rate than expected.

PMID- 9542353
TI  - Alternative techniques for the clinical assessment of foot pronation.
AB  - Clinical measurement is a fundamental component of podiatric biomechanics.
      However, recent research has seriously questioned the reliability and validity of
      the commonly used approaches to clinical measurement of foot posture. A
      reevaluation of foot-morphology measurement is therefore warranted. This article
      discusses alternative clinical techniques of measuring foot type reported in the
      literature (arch height, footprint indices, the valgus index, and navicular drop)
      that may prove to be superior to the commonly used podiatric measurement system.
      On the basis of a critical evaluation of the literature, it would appear that
      arch height and footprint indices are invalid as means of categorizing foot
      morphology, while the valgus index and navicular drop offer a number of benefits
      over traditional frontal-plane measurements. An additional clinical measurement
      suggested by the author, navicular "drift," is also introduced. The advantages,
      disadvantages, and clinical application of each of these approaches are discussed
      in detail.

PMID- 9542354
TI  - Post-traumatic first metatarsal reconstruction using coralline hydroxyapatite.
AB  - Autogenous bone grafting has been the standard approach to reconstruction of
      trauma-induced metatarsal defects. However, this treatment has well-known
      disadvantages related to the harvesting, size, shape, and availability of
      autografts. The authors used a synthetic hydroxyapatite bone-graft substitute
      manufactured from a marine coral with a morphology similar to that of cancellous
      bone in the reconstruction of a large, post-traumatic first metatarsal defect.
      The authors found grafting with coralline hydroxyapatite to be a safe and
      effective substitute for autogenous bone grafting in the post-traumatic setting.

PMID- 9542355
TI  - Rare presentation of hereditary multiple exostoses. A case report.
AB  - Hereditary multiple exostoses is a relatively uncommon disorder of endochondral
      bone characterized by the presence of multiple, cartilaginous-capped exostoses
      arising from the metaphyses. A rare presentation of hereditary multiple exostoses
      in the calcaneus of a 35-year-old man is reviewed and discussed. A brief review
      of the literature is provided, as well as a discussion of the patient's family
      history.

PMID- 9542356
TI  - Charcot's joint following Keller arthroplasty. A case report.
AB  - Neuropathic osteoarthropathy, i.e., Charcot's joint, has not previously been
      reported as a sequela of elective foot surgery. The authors present a challenging
      case of a patient with long-standing diabetes mellitus and peripheral neuropathy
      who developed neuropathic osteoarthropathy after a Keller arthroplasty for a
      recalcitrant hallux ulcer. The radiographic findings, diagnostic tests, and
      histopathology are discussed. Finally, the authors offer suggestions for surgeons
      contemplating a Keller arthroplasty for patients with peripheral neuropathy.

PMID- 9542357
TI  - Recurrent ringed lesion of the sole: erythema annulare centrifugum.

PMID- 9542358
TI  - Secondary hypertrophic osteoarthropathy.
AB  - Whenever hypertrophic osteoarthropathy is diagnosed, it is imperative to search
      for the underlying pathology. The disorder is usually associated with a primary
      pulmonary lesion and periostitis and paresthesias of the lower extremities.
      Recognizing and understanding the primary pathology is essential to the effective
      treatment of secondary hypertrophic osteoarthropathy.

PMID- 9542359
TI  - Abscess-like gouty tophus of the foot.

PMID- 9542360
TI  - Synovial sarcoma: an unusual case presentation.

PMID- 9542361
TI  - Characterization of pulsatile secretion of gonadotropin and prolactin in women
      with normal menstrual cycle, secondary amenorrhea and polycystic ovary syndrome
      (PCOS).
AB  - To characterize the episodic fluctuations of serum LH, FSH and PRL in women with
      normally cycling, secondary amenorrhea and polycystic ovary syndrome (PCOS), four
      groups of women were studied: group I (N = 8) consisted of normal women in the
      follicular phase of the cycle; group II (N = 10) of women with secondary
      amenorrhea and positive progesterone withdrawal bleeding; group III (N = 8) of
      women with secondary amenorrhea and negative progesterone withdrawal bleeding;
      group IV (N = 9), women with polycystic ovary syndrome (PCOS). Blood samples were
      obtained at 15 minute intervals for 4 hours during one admission day. Ovarian
      steroids were measured to evaluate the baseline endocrine environment in each
      group. Distinct pulsatile fluctuations of serum LH, FSH and PRL were observed in
      all subjects. These pulses showed a high degree of coincidence in LH with FSH and
      LH with PRL in each group. However, the mean (+/- SD) frequencies of LH in group
      III and group IV were significantly lower (P < 0.01) and higher (P < 0.01) than
      in group I, respectively. The mean frequencies of FSH in groups III and IV were
      lower (P < 0.05), as compared with those of group I. The mean amplitude of LH in
      group IV was significantly higher (P < 0.001) than in group I. These results
      suggest that loss of the regulatory pulsatility of gonadotropin releases may be a
      contributory cause to anovulation and secondary amenorrhea. The concomitant
      pulsatile releases of gonadotropin and PRL are essential to reproductive function
      and their regulatory controls in the follicular phase may be mediated through a
      common neuroendocrine mechanism in normal and hypogonadal women.

PMID- 9542362
TI  - Anti-GT1b and anti-GM1 antibodies can increase after stroke but neither is
      associated with late post-apoplectic epilepsy.
AB  - The role of antiganglioside antibodies (AGAs) in late post-apoplectic epilepsy
      (LPAE) was studied. Serum AGAs from 8 patients with large lobar infarctions were
      serially checked for 2.5 months. Sera from another 30 patients with fronto
      temporoparietal (FTP) or frontal (F) infarction were obtained 3 months to 3 years
      after a stroke for AGA analysis. These 30 patients were followed up for 3 years
      following their strokes to determine if LPAE developed. Results showed that 7/8
      patients with large lobar infarction showed increase in either anti-GT1b or anti
      GM1 (IgM or IgG) within a few weeks, but levels returned to the baseline 2-3
      months after stroke. LPAE occurred in 9/21 patients with FTP infarction and 5/9
      with F infarction. There was no difference in AGAs among patients with FTP and F
      infarctions. Pooled data from these 2 groups showed no correlation between AGAs
      and LPAE. These data document for the first time that anti-GT1b and anti-GM1
      antibodies can transiently increase after stroke, but their late titers are not
      associated with LPAE.

PMID- 9542363
TI  - Simultaneous determination of paraquat and diquat in urine by capillary
      electrophoresis.
AB  - Qualitative and quantitative detection of paraquat and diquat in urine was
      performed by capillary zone electrophoresis (CZE). In non-extracted urine, these
      two closely related herbicides were hydrodynamically or electrokinetically
      injected into the capillary and well separated in a acidic (pH 3.0) buffer (10 mM
      glycin, 50 mM NaCl and 20% methanol) within 8 min. The analytes can be identified
      by their respective migration time with no interfering endogeous compounds
      around. The peaks were further confirmed by their respective multi-wavelength
      scanning spectra. Limits of detection (LOD) were 0.2 and 0.1 mg/ml for PQ and DQ,
      respectively, in nonextracted urine using hydrodynamic injection. Detection
      sensitivity was greatly improved by solid phase extraction of the compounds
      followed by CZE using electro-injection under which LODs were 15 and 8 ng/ml for
      paraquat and diquat respectively. We conclude CZE is a useful method for
      laboratory diagnosis of herbicide intoxication.

PMID- 9542364
TI  - Ankle arthrography and chronic lateral ankle instability.
AB  - Sixty-five ankle arthrograms of the patients who underwent surgical
      reconstruction for their chronic ankle instability from 1987 to 1995 were studied
      retrospectively by comparing their operative findings. There were 15 cases
      (23.1%) with definite positive arthrographic findings. In the remaining 50 cases
      (76.9%), the arthrograms showed a "tear-drop" extravasation of dye beneath the
      fibular tip which we called "suspectable positive". Of these all but one, which
      had normal ligament, proved to correspond to the operative finding. As there was
      only one false positive finding among our surgical cases with both the "definite"
      and "suspectable" positive arthrograms, we concluded that ankle arthrography is
      relatively reliable and may be worth doing even in chronic cases if only for
      reference. Even when other diagnostic methods are negative, arthrography might
      help surgeons make surgical decisions in clinical symptomatic cases.

PMID- 9542365
TI  - Tear of the anterior cruciate ligament: evaluation with MR imaging.
AB  - Sixteen patients with traumatic injury to the knees were surveyed with magnetic
      resonance (MR) machines with field strength of either 0.5 Tesla (T) using head
      coil (10 cases) or 1.5 T using dedicated knee coil (6 cases). Tears of the
      anterior cruciate ligament (ACL) were found in eight cases. The other eight cases
      had injuries of the other ligaments, meniscus or bone with intact ACL. All cases
      were proved by arthroscopy. Primary and secondary signs of the ACL tears were
      evaluated by MR imaging. Primary signs included the status of ACL. Secondary
      signs consisted of bone bruise in the posterolateral tibial plateau, in the
      lateral femoral condyle, or both (so-called kissing bone bruise), fracture at the
      posterolateral tibial plateau, Segond fracture, anterior dislocation of the tibia
      (> 5 mm), buckled posterior cruciate ligament (PCL), positive PCL line and the
      deep lateral femoral notch (> 1.5 mm). Of the eight cases of the ACL tears, 5
      cases (62.5%) revealed thickening and edema of the ACL, 3 cases (37.5%) kissing
      bone bruise, 1 case (12.5%) Segond fracture, 2 cases (25%) buckled PCL, 2 cases
      (25%) deep lateral femoral notch, 2 cases (25%) anterior dislocation of the tibia
      and 0 case (0%) positive PCL line. The ACL had normal thickness of low signal
      intensity in 3 cases of chronic ACL tears (50%). Lateral meniscal tears were
      found in seven of the eight cases of ACL tears (87.5%). For the eight cases with
      intact ACL, the ACL was normal in thickness and of low signal intensity. Other
      findings were bone bruise in the lateral femoral condyle (1 case, 12.5%),
      fracture at the posterolateral tibial plateau (1 case, 12.5%), buckled PCL (1
      case, 12.5%) and positive PCL line (1 case, 12.5%). It is concluded that primary
      sign is important in the MR diagnosis of the ACL tears. Secondary signs are
      helpful but may be present in lesions with intact ACL.

PMID- 9542366
TI  - The effects of Western music on postoperative pain in Taiwan.
AB  - Music is a method nurses can use to help relieve pain, however little is known
      about its effectiveness across cultures. In this study, Western music was tested
      for its effectiveness in reducing postoperative pain in 38 Taiwanese patients,
      and its acceptability was explored. A pretest and post-test experimental design
      was used with visual analogue scales to measure sensation and distress of pain.
      Before surgery, subjects were randomly assigned to receive tape recorded music or
      the usual care. Those who were assigned to the music group chose among 5 types of
      sedative music. On postoperative Day 1 and Day 2, the effectiveness of the tape
      recorded music was investigated during 15 minutes of rest in bed. Patients were
      interviewed on Day 3 to determine their liking for the music, its calming
      effects, and the helpfulness of the music. Repeated measures analysis of variance
      showed a significant interaction between time and group in the distress of pain
      on Day 1, but not on Day 2, and in pain sensation on Day 2, but not Day 1.
      Subjects from Taiwan were similar to subjects in a previous study in the United
      States in their liking for the music, and in reports of the helpfulness of the
      music for pain sensation and distress, but fewer Taiwanese found the music
      calming, and they had different choices: more chose harp music and fewer chose
      jazz than subjects in the U.S. study, and some would prefer Buddhist hymns or
      popular songs heard in Taiwan. Findings support the use of culturally acceptable
      music in addition to analgesic medication for the sensation and distress of
      postoperative pain.

PMID- 9542367
TI  - Factors related to adolescents' perceptions of treatment outcomes in an
      adolescent health clinic.
AB  - To determine factors related to adolescents' perceived treatment outcomes of
      their health problems in an adolescent health clinic located at a college
      hospital, 246 adolescent patients between the ages of 11 and 21 who visited the
      clinic twice or more during the period January 1994 to December 1995 were
      included in this study. Information concerning adolescents' sociodemographic
      characteristics, family function, office visits and health problems of first
      visits was collected by reviewing subjects' medical and other clinic-related
      records. In addition, a structured questionnaire was mailed to assess subjects'
      satisfaction with physicians and the environment and services provided by the
      clinic as well as their perceived treatment outcomes. 148 patients completed the
      questionnaire, a response rate of 60.2%. Most of the respondents were in late
      stage adolescence (71.0%) and were in school (71.0%). About half of respondents
      had normal family function, while the other half had moderate or severe family
      dysfunction. Most of the health problems of respondents were acute (64.2%) and
      were biological (76.4%) conditions. Most of the respondents were satisfied with
      the various characteristics of physicians except confidentiality emphasized by
      the physicians, while many fewer respondents were satisfied with the environment
      and services provided by the clinic. Family function, physicians' respect toward
      the adolescents, and the adolescents' satisfaction with the services provided in
      general were the factors significantly related to adolescents' perceived
      treatment outcomes based on a stepwise, multiple logistic regression analysis. We
      conclude that efforts to provided could result in better adolescent perceived
      treatment outcomes.

PMID- 9542368
TI  - Shaken baby syndrome.
AB  - Fourteen cases of shaken baby syndrome seen between 1993 to 1997 at the Kaohsiung
      Medical College Hospital were reviewed. The common clinical presentations were
      seizure, respiratory problem and disturbed consciousness. The signs and symptoms
      of this form of head trauma were nonspecific. The findings may mimic infection,
      intoxication, seizure disorder or metabolic abnormalities. The CT scan is the
      most common diagnostic tool in cases of suspected shaken baby syndrome. The
      common CT findings were acute subdural hematoma followed by chronic subdural
      hematoma and subarachnoid hemorrhage. One infant died due to delay in seeking
      medical help. Five patients sustained significant morbidity which included
      developmental delay, seizure, motor deficit and visual impairment. Early
      recognition and prompt treatment were key to the overall success of case
      management. The incidence of shaken baby syndrome can be reduced through public
      awareness and education of the parents not to shake the baby.

PMID- 9542369
TI  - Cavernous sinus syndrome and hepatoma metastasis.
AB  - A 46-year-old man presented with left cavernous sinus syndrome and subsequent
      right leg pain proved clear cell type hepatocellular carcinoma metastasis. An
      initial liver function test was normal and alpha-fetoprotein was only 15 ng/ml
      but they increased rapidly and he progressed to hepatic failure 2 weeks later.
      Therefore, a subclinical hepatoma with metastasis should be differentiated in
      cavernous sinus syndrome, even in cases of normal hepatic enzymes, because
      hepatoma is prevalent in Taiwan.

PMID- 9542370
TI  - Gastric duplication cyst: report of a case.
AB  - Gastric duplication cyst is a rare disease entity, especially in the adult
      population. We report a case of 33-year-old female patient who presented with
      epigastric pain, postprandial fullness and nausea for the past several months.
      Gastroendoscopy showed a submucosal mass with normal overlying gastric mucosa.
      Upper gastrointestinal series confirmed a extrinsic compression of mass in the
      fundus of the stomach. Endoscopic ultrasonography and computerized tomography
      demonstrated the lesion to be a cyst in nature. The surgical procedure consisted
      of total excision without violation of the gastric lumen. Gastric mucosa was
      found by the histologic study of the excised cyst.

PMID- 9542371
TI  - [The contributions of occupational medicine to ergonomics].
AB  - Major contributions to the development of ergonomics, originating from
      observations, studies, research and applications in numerous working situations
      in the occupational health area, are presented and discussed in an analytical and
      concise manner. Ergonomics can provide an extremely useful conceptual and
      methodological approach provided it complies with the trends developed by the
      European Coal and Steel Commission in the past ten years for the coal and steel
      industry and now adopted by the International Ergonomics Association. Otherwise
      prevention of occupational hazards would be reduced to early diagnosis only,
      relinquishing all prospects of primary prevention which, if correctly applied,
      can only be achieved via an anthropocentric design concept. Therefore new
      epistemological choices, new theories, methods and design procedures need to be
      widely implemented so that they can be correctly synthetized, in accordance with
      the centrality, the values and the aspirations of the human operator in complex
      systems.

PMID- 9542372
TI  - [Biomechanical pathology of the upper limb: a new epidemic?].
AB  - Work-related upper limb disorders are one leading occupational diseases in many
      industrialized countries. The paper reviews the evidence of work-relatedness of
      the most common upper limb disorders (namely carpal tunnel syndrome, hand-wrist
      and shoulder tendinitis, trapezius myalgia, hand hammer syndrome). Attention is
      drawn to the difference in the number of reported cases in Italy and other
      countries, assuming, as an underlying cause, underreporting of such conditions in
      Italy.

PMID- 9542373
TI  - [The health risks of exposure to electromagnetic fields in work environments].
AB  - In the last few years the debate on possible health risks of electromagnetic
      fields has focused on specific sources, namely power lines and, more recently,
      base stations for cellular telephones. This has drastically diverted the
      attention of the research and prevention community towards residential exposures.
      On the other hand, the increasing number of technological process exploiting or
      generating electromagnetic fields requires greater attention to exposures at the
      workplace. The scope of research in this area is vast because of different
      emission characteristics of the sources, different interaction mechanisms at
      various frequencies, and different effects that have been identified or
      hypothesized. The paper presents an overview of health problems involved in
      exposure to electromagnetic fields at the workplace. Different frequency ranges
      and related sources are considered separately. In particular, the different
      levels of knowledge are noted and areas requiring further research are
      identified.

PMID- 9542374
TI  - [The concentration levels of airborne quartz at an urban site].
AB  - The IARC has recently included crystalline silica among substances considered
      carcinogenic for man. This new evaluation immediately posed the need to measure
      the exposure levels of the general population. The paper reports the results of
      measurements of the concentrations of quartz (i.e., the most common form of
      crystalline silica) in a location in the urban area of Rome. First we studied the
      respirable fractions of the airborne particles (PM10) sampled in the Spring of
      1996 with a cascade impactor, which were characterized using a scanning electron
      microscope equipped with an X-ray microprobe. Ten components were identified
      including total silica (crystalline and amorphous), which was present in a
      percentage of 3.7% on average. On the basis of these data a methodological study
      was undertaken of the concentration of quartz in the historic series of PM10
      sampled daily at the same site by means of an AMP instrument (Airborne Particles
      Monitor). The filters of mixed cellulose esters on which the PM10 was collected
      were incinerated at low temperature in oxygen plasma to eliminate the organic
      component. The residue was deposited on silver filters which were read with a
      conventional X-ray diffractometer in order to determine the quantity of quartz.
      We analyzed 28 filters from four representative weeks of the four seasons of
      1994, the year in which systematic sampling was initiated. The results showed a
      mean weekly concentration of airborne quartz of between 0.6 and 1.5
      micrograms/Nmc, which gives a percentage over PM10 of 1.7 and 3.4 respectively.
      These data substantially agree with previous results obtained with electron
      microscopy and show that the levels of quartz in the urban atmosphere under study
      were about one hundred times lower than the TLV currently recommended by the
      ACGIH for working environments (100 micrograms/Nmc) and which are also in force
      in Italy.

PMID- 9542375
TI  - [Allergic pathology due to enzymes: a case report of asthma due to pectinase
      (polygalacturonase)].
AB  - The paper described the case of a worker handling pectinase, an enzyme used in
      the manufacture of food additives. This enzyme is a carbohydrase
      (polygalacturonase) obtained by extraction, and consists of three active phases.
      After little more than a year at the job, the subject complained of bouts of
      asthma, especially when she had to weigh the enzyme in dust form. Symptoms
      appeared even when this operation was performed by others near her work station.
      An allergological examination revealed skin hypersensitivity to the enzyme,
      without atopy. The methods of preparing the tests performed are described. The
      authors stress the need to perform similar investigations on other exposed
      workers in order to assess the allergogenic potential of the substance and adjust
      environmental preventive measures accordingly.

PMID- 9542376
TI  - Epidemiological study on knowledge, attitudes and behaviour of health care
      workers with respect to HIV infection.
AB  - To analyse knowledge, perception of risk, attitudes and behaviour towards HIV
      infection among health workers in two hospitals in the North-East of Italy, we
      sent all health care workers who were working in direct contact with patients an
      anonymous self-administered questionnaire covering personal and occupational
      data, perception and knowledge of risk, behaviour in routine activities,
      attitudes towards and care of HIV patients. The response rate was 70.06%. The
      perception of the risk of acquiring HIV infection was influenced by occupational
      qualification, by work unit and by having cared for a HIV-positive patient.
      Scientific knowledge about transmissibility of HIV infection was poor and 11.3%
      of the staff did not know the Universal Precautions. 28.3% behaved correctly in
      recapping needles, but with patients considered not at risk 29.9% did not use any
      protection in drawing venous blood. A significant portion of staff showed low
      willingness to care for HIV-positive patients. We found a high mean perception of
      the risk of contracting HIV infection through occupational exposure; health
      workers overestimated the specific risk and wrong behavioural attitudes
      persisted. To conclude, more attention should be paid to educational programs for
      health workers.

PMID- 9542377
TI  - [The presence of asbestos on board ships: optical microscopy as a research
      instrument].
AB  - Identification of asbestos in many different kinds of bulk materials was
      performed by means of optical microscopy and the results are reported in the
      present paper. Some hundreds of various samples taken aboard ships were analysed:
      panels, laggings, spray insulations, etc. These analyses were required to be not
      only reliable but also rapid. The results demonstrated the high reliability as
      well as the rapidity of the technique. Using both the well-known dispersion
      staining technique (with central stop objectives or with dark field condensers)
      and phase-contrast analyses on the same polarizing microscope, we carried out
      numerous checks on the optical properties of the fibres. Not only were dispersion
      staining colours detected but also refractive index, elongation and extinction
      signs, in order to obtain an absolutely certain identification. The Italian laws
      which deal with the asbestos detection discourage the use of the optical
      microscope because of its presumed unreliability. This paper tends to demonstrate
      that Italian laws underestimate the potential of the optical microscope. Optical
      microscopy is probably the only technique that is reliable, inexpensive and rapid
      at the same time.

PMID- 9542378
TI  - Practice management contracts/illegal fee-splitting.

PMID- 9542379
TI  - A physician's primer for managed care contracting.

PMID- 9542380
TI  - MSMSNET a "hit".

PMID- 9542381
TI  - "Back to sleep" campaign a success. SIDS rates drop due to information,
      education.

PMID- 9542382
TI  - Staying ahead financially. Reimbursement tips for a changing environment.
AB  - Physicians' primary goal is to give good care to their patients. But like other
      managers in changing times, they face big challenges to achieving their goals.
      Major national stressors for all professionals today, experts report, are time
      and money. MSMS leaders, participating in strategic planning sessions this past
      summer and fall, agreed, ranking reimbursement/revenue problems as second on
      their list of concerns, right behind autonomy as physicians.

PMID- 9542383
TI  - Area hospital receives a "breath of fresh air".

PMID- 9542384
TI  - [Control of apparatus in anesthesia. Gruppo di Studio SAARTI per la Sicurezza in
      Anestesia e Terapia Intensiva].

PMID- 9542385
TI  - [Recommendations for basic monitoring of patients during anesthesia. Gruppo di
      Studio SAARTI per la Sicurezza in Anestesia e Terapia Intensiva].

PMID- 9542386
TI  - [Informed consent in anesthesia. In accordance with the general guidelines
      proposed by the European Board of Anesthesiologists (EBA)].

PMID- 9542387
TI  - [Recommendations for post-anesthetic care. Gruppo di Studio SAARTI per la
      Sicurezza in Anestesia e Terapia Intensiva].

PMID- 9542389
TI  - [Recommendations for anesthesia in the day hospital. Gruppo di Studio SAARTI per
      la Sicurezza in Anestesia e Terapia Intensiva].

PMID- 9542388
TI  - [Recommendations on malignant hyperthermia. Gruppo di Studio SAARTI per la
      Sicurezza in Anestesia e Terapia Intensiva].

PMID- 9542390
TI  - [The HIV positive patient in anesthesia and intensive care. Organizational,
      medico-legal aspects. Gruppo di Studio SAARTI per la Sicurezza in Anestesia e
      Terapia Intensiva].

PMID- 9542391
TI  - Treatment of the epileptic patient in the dental office.
AB  - Epilepsy is a relatively common problem in children, adults and the elderly.
      Dentists need to be familiar with the various manifestations of the disease, the
      anticonvulsant medications (AEDs) the patients are taking, and the complications
      and side effects of these drugs. In this article the types of seizures and AEDs
      in common use are described. Guidelines for treatment planning are given.
      Recommendations are made for managing the patient who has a seizure in the dental
      office.

PMID- 9542392
TI  - Dental caries in developing countries. Preventive and restorative approaches to
      treatment.
AB  - The rate of dental caries in developing countries is rising. Because more than 80
      percent of the world's children live in these countries, this alarming trend is
      of great concern from a public health standpoint. Currently, most dental care in
      developing nations consists of dental surgery in urban areas. Decay is usually
      left untreated until it becomes so extensive and/or painful that extraction is
      the only option. Traditional approaches to treating carious lesions have met with
      marginal success. There is a need for widespread implementation of preventive
      strategies, which have proven extremely effective in industrialized nations.
      Also, promising new techniques and materials are being developed that are
      enabling dentists and dental personnel to make less costly treatment of dental
      caries more readily available to underserved populations.

PMID- 9542393
TI  - Recommendations for fluoride use in children. A review.
AB  - Fluoride has played a significant role in the improvement of the oral health of
      all Americans. Because of its effectiveness, cost and frequency of exposure,
      water fluoridation is the preferred method of delivery. Today, many products
      containing fluoride are available over the counter and as prescription items. The
      potential for exposure to multiple sources of fluoride has increased. Therefore,
      practitioners should prescribe fluoride therapy based on an understanding of
      patients' total exposure to fluoride and the need for additional amounts.

PMID- 9542394
TI  - When children put their fingers in their mouths. Should parents and dentists
      care?
AB  - We have heard mothers tell their children not to stick their fingers in their
      mouths because they will get sick. Medical and dental professionals know this is
      true. Oral habits like thumb sucking and nail biting can damage the structure of
      the mouth and can lead to the spread of infectious diseases.

PMID- 9542395
TI  - [One general pattern in the development of pathologic processes in the heart in
      various types of myocardial involvement].
AB  - Experiments on 50 rabbits were made to study left and right ventricular function
      and ultrastructure of the heart in its diffuse and focal disease, overload of the
      intact heart. In the middle stage of the above conditions there was a distinct
      dyscoordination of the heart function and the growth of differences in the heart
      ventricles ultrastructures. This phenomenon may underlie the rise of intracardiac
      and general hemodynamic disturbances.

PMID- 9542396
TI  - [Pathogenesis, diagnosis and therapy of heart disease caused by enteroviruses
      (molecular biological study)].
AB  - Molecular hybridization studies have demonstrated that human enteroviruses,
      including group B coxsackieviruses (CVB), are detectable in myocardial tissue of
      patients with acute and chronic myocarditis. As well, such infections are
      observed in some patients with end-stage dilated cardiomyopathy indicating the
      possibility of persistent heart muscle infection. Enterovirus persistence in the
      human heart is supported by the discovery in various murine models of chronic
      myocarditis, demonstrating that coxsackievirus B3 (CVB3), typically a cytolytic
      virus, is capable of evading immunological surveillance in a host-dependent
      manner. Currently attention is focused on the analysis of molecular mechanisms of
      virus persistence, the characterization of viral and host factors and their
      impact in determining the natural course of myocardial enterovirus infections.
      The evidence for a causal linkage of enterovirus infection with heart muscle
      diseases has emerged therapeutic implications. From the view of a virologist,
      immunosuppressive treatment of patients revealing enterovirus infection in the
      myocardium with steroids is clearly contraindicated. The evaluation of potent
      antiviral agents, such as interferons, in established in vitro and in vivo model
      systems of enterovirus infection is expected to contribute significantly to new
      therapeutic strategies in human enteroviral heart disease.

PMID- 9542397
TI  - [Visceral afferentation and nociception].
AB  - The authors present the results of acute cat experiments in which characteristics
      of the heart afferent reactions were studied by registration of evoked
      potentials. It was shown that in occlusion of the coronary arteries afferent and
      vegetative reactions did not correlate with development of cardial nociception.
      This was related to opiate mechanisms of the intraorgan regulation. In myocardial
      histotoxic hypoxia intraorgan mechanisms of the heart afferent reactions were
      destroyed.

PMID- 9542398
TI  - [Functional disturbances of the immune system in rheumatic diseases and their
      dynamics in the context of pathogenetic therapy].
AB  - Immunological investigations in patients with rheumatic diseases (rheumatoid
      arthritis, Reiter's disease, infectious endocarditis, rheumatic heart disease)
      evidence that the time of onset of different immunologic pathogenetic mechanisms
      was the same. Immunological rehabilitation was achieved by different therapeutic
      methods: drugs, plasmapheresis, hemosorption, electrophoresis, ultrasound. In
      experiments it was beta-1-trophoblastic glycoprotein.

PMID- 9542399
TI  - [Use of thymogen in the treatment of various forms of acute abdominal disorders
      in an experiment].
AB  - The authors have carried out experimental studies of thymogen action on the
      course of acute pancreatitis and acute peritonitis in white albino rat males. The
      preparation was introduced into the abdominal cavity early after the modeling and
      every 24 hours for 5 days. The results of the trial demonstrate that the degree
      of autoenzyme aggression (the data of blood serum alpha-amylolytic activity
      control) and the content of lipid peroxidation products (assessment of malonic
      dialdehyde quantity in tissue homogenate) were low in the experimental group as
      compared to the untreated animals. In the experimental group less pronounced
      depression of antiradical activity (superoxide dismutase and catalase activity
      control) was found, leukocytosis and leukocyte intoxication index were
      diminished. Thus, the efficiency of thymogen in acute inflammatory and
      destructive abdominal diseases has been proved.

PMID- 9542400
TI  - [Ultrastructure of human peripheral blood lymphocytes as affected by extreme
      factors].
AB  - Characteristic features of ultrastructure of peripheral blood lymphocytes were
      studied in males aged 20-24 years performing hard muscular labour under emotional
      stress in unfavourable climate conditions. It was found that a prolonged exposure
      (> 3 mo) to the extreme factors brings about characteristic changes in
      ultrastructure of peripheral blood lymphocytes: a complicated shape of the
      lymphocytic nuclei, plasma membrane labilization, partial or total destruction of
      the mitochondrial cristae in most of the cells. It was suggested that all these
      changes were morphological criteria of reduced resistance of the body in response
      to extreme conditions. It was also established that autumn is less favourable for
      adaptation to extreme physical and climate conditions than summer.

PMID- 9542401
TI  - [Ultrastructural characteristics of nonphlogogenic and phlogogenic reaction of
      mono- and polynuclear phagocytes in their interaction with Staphylococcus
      aureus].
AB  - Antibacterial function of neutrophil leukocytes and peritoneal macrophages in
      their interaction with massive doses of Staphylococcus aureus (25 x 10(6) and 25
      x 10(8) microorganisms) has been studied in the experiment in vivo. Two types of
      antibacterial reaction of phagocytes has been found, i.e. nonphlogogenic
      (physiological) and phlogogenic (inflammatory). nonphlogogenic type was
      characterized by marked antibacterial influence of phagocytes. phlogogenic
      reaction was accompanied by an increase of failure of phagocyte function, by
      their self-damage and break-up that leads to a decrease of their antibacterial
      activity followed by the inflammation.

PMID- 9542402
TI  - [Change in the content of alpha-fetoprotein and sex steroid hormones in the blood
      of rabbits in fever or subnormal temperature].
AB  - In experiments on rabbits, changes in the content of alpha-fetoprotein, estradiol
      and progesterone in blood serum in fever and subnormal temperature simulated with
      the use of pyrogenal and Freund's complete adjuvant were studied. The
      concentration of alpha-fetoprotein decreased and that of estradiol and
      progesterone increased. The results were analyzed in terms of the return of
      certain signs and properties in disease to the period of antenatal ontogenesis. A
      possible relation between the changes in alpha-fetoprotein in fever, subnormal
      temperature and immune, hormonal mechanisms of the thermoregulatory disorder was
      hypothesized.

PMID- 9542403
TI  - [Role of vascular and cellular complexes of nerve tissue in the mechanism of anti
      edema action of phenothiazine derivatives].
AB  - The stochastic model has been designed enabling elucidation of structural
      components of the nervous tissue involved in antiedema mechanism of phenotiazine
      derivatives in conditions of negative effects of edematous factors. The
      stochastic model helped detection of basic control structures in the tested
      morphofunctional complexes, provided quantitative assessment of the effects of
      interrelations of the morphofunctional structures in response to the interfering
      factors.

PMID- 9542404
TI  - [Vasotropic action of met-enkephalin in sympathetic nervous system block].
AB  - Administration of met-enkephalin to anesthetized cats promoted inhibition of the
      heart rate, weakening of the vagus chronotropic effect with changes of its
      functional structure consisting of suppression of the inhibitory tonic effect and
      potentiating synchronizing component. The comparison of the peptide's vagotropic
      action in the initial conditions versus in the block of the sympathetic nervous
      system induced by obsidan, guanethidine or reserpine allows the conclusion that
      the effect of met-enkephalin on the baseline heart rate, strength of the vagus
      chronotropic effect and its tonic component stems from weakened sympathetic
      effects on the heart, whereas potentiation of the synchronizing vagus component
      is achieved through the peptides effects in the limits of vagus regulation
      system.

PMID- 9542405
TI  - [The immune system and pathology (continuation). Chapter 4. Pathologic processes
      with involvement of the immune system. Pathogenetic methods of immunocorrective
      therapy].

PMID- 9542406
TI  - [Glucocorticoids and myocardial infarction].

PMID- 9542407
TI  - Keynote address: PDA/FDA joint conference.

PMID- 9542408
TI  - Evaluation of high-temperature and short-time sterilization of injection ampules
      by microwave heating.
AB  - The high-temperature and short-time sterilization by microwave heating with a
      continuous microwave sterilizer (MWS) was evaluated. The evaluation were
      performed with respect to: [1] lethal effect against microorganisms corresponding
      to F-value, and [2] reliability of MWS sterilization process. Bacillus
      stearothermophilus ATCC 7953 spores were used as the biological indicator and the
      heat-resistance of spores was evaluated with conventional heating method (121-129
      degrees C). In MWS sterilization (125-135 degrees C), the actual lethal effect
      against B. stearothermophilus spores was almost in agreement with the F-value and
      the survival curve against the F-value was quite consistent with that for the
      autoclave. These results suggest that the actual lethal effect could be estimated
      by the F-value with heat-resistance parameters of spores from lower than actual
      temperatures and that there was no nonthermal effect of the microwave on B.
      stearothermophilus spores. The reliability of sterilization with the MWS was
      confirmed using more than 25,000 test ampules containing biological indicators.
      All biological indicators were killed, thus the present study shows that the MWS
      was completely reliable for all ampules.

PMID- 9542409
TI  - Application of a newly developed hydrogen peroxide vapor phase sensor to HPV
      sterilizer.
AB  - A new type of concentration sensor for hydrogen peroxide vapor has been developed
      by making use of a semiconductor. Output from the vapor sensor has been shown to
      have a good linear relationship with the logarithm of the concentration of
      hydrogen peroxide vapor. Concentration of hydrogen peroxide vapor introduced into
      the sterilization chamber could be kept constant by monitoring the concentration
      of the hydrogen peroxide vapor continuously and controlling the vapor supply.
      Temperature and humidity have also been kept constant. D-values for B.
      stearothermophilus ATCC 12980 at various concentrations of hydrogen peroxide
      vapor have been determined by using the combination system of the hydrogen
      peroxide vapor sensor, the hydrogen peroxide vapor supplier, thermosensor and
      humidity sensor. D-values at the temperature of 30 degrees C and the absolute
      humidity of 0.7 mg H2O/L thus obtained, were 0.2 minutes at hydrogen peroxide
      concentration of 600 ppm and 1.2 minutes at 200 ppm at the temperature of 30
      degrees C and 0.7 mg/L absolute humidity. D-values for B. stearothermophilus ATCC
      12980 at various temperatures, humidity and levels of hydrogen peroxide
      concentration have also been determined. These fundamental data indicate that the
      sterilization by hydrogen peroxide vapor can be validated as precisely as steam
      sterilization by measuring and controlling the concentration of hydrogen peroxide
      vapor using a combination of the hydrogen peroxide concentration sensor and the
      vapor generator. Influence of temperature and humidity have also been studied.
      The hydrogen peroxide sensor has been calibrated and standardized by using the
      standard hydrogen peroxide vapor whose concentration has been determined by
      calculating partial pressure of hydrogen peroxide over the water-hydrogen
      peroxide solution.

PMID- 9542410
TI  - Silicone absorption of elastomeric closures--an accelerated study.
AB  - There is a trend in the parenteral industry to move from the use of elastomeric
      closures which are washed, siliconized, dried and sterilized in-house at the
      pharmaceutical manufacturers' site to pre-prepared closures purchased from the
      closure supplier. This preparation can consist of washing to reduce particle-load
      and bioburden, siliconization, placement in ready-to-sterilize bags and may
      eventually extend to sterilization by steam autoclave or gamma irradiation. Since
      silicone oil lubrication is critical to the processability/machinability of
      closures, research was designed to investigate this phenomenon in closures
      prepared using the Westar RS (Ready-to-Sterilize) process. This paper presents
      the data gathered in a study of the characteristic of silicone absorption into
      elastomeric closures under accelerated conditions. Variables such as silicone
      viscosity, rubber formulation, effect of sterilization and others are considered.

PMID- 9542411
TI  - Storage stability of stabilized MLV and REV liposomes containing sodium
      methotrexate (aqueous & lyophilized).
AB  - Multilamellar and unilamellar liposomes containing sodium methotrexate (MTX) were
      prepared by thin film hydration and reverse-phase evaporation methods.
      Encapsulation efficiency and release of MTX from liposomes at 4 degrees C, 25
      degrees C and 37 degrees C were determined. When stored at 25 degrees C the
      liposomes lost 33% MTX after one month. To stabilize liposomes, they were freeze
      dried in presence of different amounts of cryoprotectants (trehalose, PEG 10,000,
      PEG 20,000, and a mixture of trehalose-PEG 20,000). Measurements showed that the
      mixture of trehalose-PEG 20,000 imparted an MTX retention of about 70% after
      lyophilization. Stability tests of the lyophilized product at 4 degrees C, 25
      degrees C and 37 degrees C demonstrated they were fairly stable even at 37
      degrees C, indicating their potential use in commercial applications.

PMID- 9542412
TI  - Determining whether a product is steam sterilizable.
AB  - The FDA has issued proposed regulations to require that manufacturer's evaluate
      the "steam sterilizability" of parenteral products. There are many different ways
      to assess sterilizability. Within a company, it is helpful to standardize the
      methodology used to determine whether the product should be terminally
      sterilized. The following is one approach to determining product sterilizability.
      This approach is also depicted in a flow chart (Figure 4).

PMID- 9542413
TI  - Bacterial cell size and surface charge characteristics relevant to filter
      validation studies.
AB  - There are two recognized mechanisms whereby organisms are retained by liquid
      filters; namely, sieve-retention and adsorption. The efficiency of each may be
      influenced by the organism, suspending milieu, and by the filtration conditions.
      Validations of sterilizing filtrations require the use of organism suspensions in
      product-specific media. However, where the product is bactericidal to the
      challenge organism(s), surrogate solutions may be required. The ideal surrogate
      solution would minimize adsorptive retention, ensuring that the sterilizing
      action of the filter under consideration is the consequence of sieve-retention.
      This review explores the impact that various physicochemical factors may have on
      bacterial cell size and cell surface characteristics. An understanding of
      interactions among challenge bacteria, suspending fluid, and filter medium is
      essential for the development of surrogate solutions that provide a "worst case"
      mileu for filter validation studies or a "placebo," non-inhibitory challenge
      solution.

PMID- 9542414
TI  - Pharmaceutical laboratory compliance--manufacturer's view.

PMID- 9542415
TI  - Experimental evaluations of diffusive airflow integrity testing.

PMID- 9542416
TI  - [New trends in the management of asthma. Satellite Symposium of the 24th Congress
      of the German Society of Allergology. Hamburg, 6 September 1997].

PMID- 9542417
TI  - Pediatric nuclear medicine: a practical approach.
AB  - This paper is devoted to the practical aspects of pediatric nuclear medicine,
      particularly the controversy about drug sedation. The authors conclude that drug
      sedation should be exceptionally used. There is an alternative way, consisting in
      an adequate approach of the patient: good information to the parents and the
      child; taking care of the child's environment, starting from the first contacts
      in the waiting room; specific education of technologists: this includes
      injections and blood sampling, but also proper handling of the child during the
      procedure and adequate psychological attitudes toward child and parents. Taking
      these factors into account, it is exceptional that a test has to be postponed
      because of the lack of collaboration of the patient; good quality images, using
      the recommended paediatric amounts of radioactivity can be achieved even for
      procedures of prolonged duration.

PMID- 9542418
TI  - Assessment of gastro-esophageal dysfunction in children.
AB  - Scintigraphic methods to assess esophageal transit, gastro-esophageal reflux and
      gastric emptying are widely used in pediatric patients. This review describes the
      methodology and considers the clinical application of these techniques as well as
      the utility of alternative diagnostic studies.

PMID- 9542419
TI  - PET applications in pediatrics.
AB  - This article summarizes the major PET studies which have been performed in
      pediatric patients to elucidate and characterize diseases and normal development.
      Issues special for the application of the technique in children, such as
      dosimetry, patient preparation, and image acquisition are discussed. Studies of
      central nervous system (CNS) development and pathology, including epilepsy,
      intraventricular hemorrhage, neonatal asphyxia, tumors, and effects on the CNS
      from treatment of other tumors are reviewed. These have contributed information
      fundamental to our understanding of CNS development and pathology. PET
      investigations into the pathophysiology of congenital heart disease have begun
      and hold great promise to aid our understanding of these conditions. The second
      major area in which PET has been applied is the study of non CNS neoplasms.
      Neuroblastoma has been investigated with tracers which explore basic biochemical
      features which characterize this tumor, as well as with tracers which explore
      biochemical events relatively specific for this malignancy. Other common and
      uncommon tumors of childhood are discussed. The PET technique has been shown
      useful for answering questions of clinical relevance for the management of these
      uncommon neoplasms. PET, using tracers that reflect basic metabolic processes, is
      likely to continue to aid our understanding of many pediatric diseases and may
      gain more widespread clinical acceptance as the technology continues to
      disseminate rapidly.

PMID- 9542420
TI  - Lung scintigraphy in the assessment of recurrent bronchitis and pneumonia in
      children.
AB  - Recurrent bronchitis and pneumonia in childhood are a significant factor in
      predisposing adults to chronic respiratory disease. Lung scintigraphy in children
      with recurrent respiratory problems very frequently shows regional abnormalities,
      even in the absence of radiological signs: the main problem being the correct
      clinical use of such a high sensitivity. Structural changes, also at the
      histological level, are accompanied by functional disturbances that cause lung
      scan abnormalities to become stable with time and are very likely responsible for
      persisting disease in adulthood: the above condition needs to be identified by
      means of follow-up scintigraphies. Moreover, any chronic respiratory condition
      that has already been diagnosed, like cystic-fibrosis, bronchiectasis,
      bronchopulmonary malformations, lung fibrosis, should be assessed and followed-up
      by means of lung scintigraphy. Suspected radiotransparent foreign-body
      inhalation, radiographical hyperlucencies (compensatory or pathological
      emphysema?), functional assessment before lung surgery, suspected mucociliary
      function impairment, suspected interstitial pneumonia, pre-bronchographic or
      angiographic assessment, all of the above conditions represent important
      indications to lung scintigraphy in children. Finally, it is wise pointing out
      that, in order to avoid false positive results towards the diagnosis of
      structural disease, any easily reversible functional impairment should be removed
      before the scan, by proper patient preparation: in children this is done by at
      least aerosol therapy with beta-agonists, local steroids and mucolytics for 1
      week-10 days.

PMID- 9542421
TI  - Economic issue in pediatric nuclear medicine: cortical scanning of acute
      pyelonephritis.
AB  - Pediatric nuclear medicine, in order to survive, must be innovative in finding
      ways of competing with other pediatric imaging subspecialties for the health care
      dollars. Newer radiopharmaceuticals and imaging methods that are time-effective
      in answering clinical problems and cost-effective in attracting the health care
      providers are ways of accomplishing this difficult task. Renal cortical scanning
      for the diagnosis of acute pyelonephritis is presented as an example of an
      existing nuclear medicine study that is accurate and cost-effective, but has not
      yet taken a major place in the imaging armamentarium. In this discussion, the
      cortical scan is endorsed as the primary imaging tool for children presenting
      with acute urinary infection.

PMID- 9542422
TI  - Inflammatory bowel disease in pediatric patients.
AB  - Optimal management of chronic idiopathic inflammatory bowel disease requires
      determination of disease localization and intensity. Scintigraphy with the use of
      99mTc-HMPAO-White Blood Cells (99mTc-HMPAO-WBC) is a relatively new noninvasive
      nuclear medicine procedure. We have evaluated more than 230 children and have
      found a high correspondence between the disease distribution shown by the 99mTc
      HMPAO-WBC scan and that shown by endoscopic, radiologic, or surgical methods.
      Additionally the 99mTc-HMPAO-WBC scan has the ability of identifying extra
      intestinal site of inflammation, such as appendicitis and others. The erythrocyte
      sedimentation rate, the most frequently used indicator of disease activity in the
      clinical setting, has better correlation with the scan scores than the clinical
      activity index. The 99mTc-HMPAO-WBC scan is reliable in differentiating Crohn's
      disease from ulcerative colitis. Some patients because of unequivocal
      demonstrable small bowel uptake are reclassified from ulcerative colitis to
      Crohn's disease. The medication regimen is frequently altered because of the
      intensity of uptake displayed by the 99mTc-HMPAO-WBC scan. It is a practical and
      safe study even in an acutely ill patient who may not tolerate endoscopic or
      radiological study. At our institution, the 99mTc-HMPAO-WBC scan is now part of
      the initial evaluation, and follow-up of patients with inflammatory bowel
      disease. In conclusion the 99mTc-HMPAO-WBC is excellent for the detection,
      localization and characterization of inflammatory bowel disease in children.
      Compared with the other methods of investigation this study requires no bowel
      preparation, is noninvasive and has excellent diagnostic accuracy.

PMID- 9542423
TI  - Pediatric nuclear oncology.
AB  - Nuclear medicine plays an important and increasing role in the management of
      childhood malignancy. This is particularly true in the solid tumours of
      childhood. It is also helpful in the management of the complications of cancer
      treatment such as the infections which often accompany immune suppression in
      oncology patients. Scintigraphy is a complementary investigation to other
      radiological techniques and adds the functional dimension to anatomical
      investigations such as CT, MRI and ultrasound. Scintigraphy is used in the
      initial diagnosis, staging, assessment of tumour response to treatment, detection
      of recurrence and the diagnosis of complications. In selected malignancies
      radionuclides are also used in treatment. This review discusses the technical
      considerations relating to children and the specific techniques relating to
      pediatric oncology. Specific tumours and the various applications of
      radionuclides are discussed in particular lymphoma, primary bone tumours, soft
      tissue sarcomas, neuroblastoma, Iangerhan's cell histiocytosis, Wilms' tumour,
      brain tumours and leukemia. Uncommon tumours are also discussed and how
      radionuclides are useful in the investigation of various complications which
      occur in oncology patients.

PMID- 9542424
TI  - [Hemodynamic monitoring: Swan-Ganz catheter].

PMID- 9542425
TI  - [Mechanical ventilation].

PMID- 9542426
TI  - [Acute myocardial infarct].

PMID- 9542427
TI  - [General assessment of the trauma patient].

PMID- 9542428
TI  - [Poisoning].

PMID- 9542429
TI  - [Changes of the level of consciousness: coma and related conditions].

PMID- 9542430
TI  - [Immediate postoperative management].

PMID- 9542431
TI  - [Multiple organ dysfunction syndrome].

PMID- 9542432
TI  - [Continuous education in cardiology. Education Commission, Spanish Society of
      Cardiology].

PMID- 9542433
TI  - [Structure and function of the heart].

PMID- 9542434
TI  - [Cardiac tumors (II). Malignant primary tumors. Metastatic tumors. Carcinoid
      tumor].
AB  - Heart neoplasms are of increasing interest among clinicians and surgeons. A
      review of primary malignant cardiac tumors, secondary cardiac tumors and
      carcinoid heart tumors is presented, with special reference to their pathological
      and surgical aspects. Primary malignant heart tumors represent about 25% of all
      cardiac tumors, the great majority are sarcomas and the whole family of this
      group is described including angiosarcoma, rhabdomyosarcoma, fibrosarcoma,
      leiomyosarcoma, liposarcoma, neurogenic sarcoma, synovial sarcoma and
      osteosarcoma; mesothelioma, lymphoma, malignant teratoma and thymoma are also
      included. Metastatic heart tumors are 20-40 times more common than primary
      malignancies, their behavior and more relevant aspects in diagnostic and surgical
      therapy are mentioned. Carcinoid heart tumors represent a distinctive entity and
      are discussed individually.

PMID- 9542435
TI  - [The value of cardiac troponin I as diagnostic test in the study of chest pain].
AB  - BACKGROUND AND OBJECTIVES: Cardiac troponin I is a highly sensitive and specific
      myocardial injury marker. We have analyzed the use of cardiac troponin I values
      in the diagnosis of coronary artery disease, in previously healthy patients who
      developed chest pain with inconclusive analytical and ECG diagnostic findings.
      PATIENTS, MATERIAL AND METHODS: A one year cross-sectional consecutive study was
      conducted, in a total of 37 patients with no previously known heart disease who
      were admitted to the coronary unit for suspected anginal chest pain with normal
      cardiac enzymes and ECG. Abnormal cardiac troponin I levels at admission were
      defined as > or = 0.4 ng/ml, and were compared with coronary angiography or
      exercise test results and related to the duration of pain and the time from the
      appearance of symptoms to blood extraction. RESULTS: Thirty-three of the 37
      initially included patients were studied. Coronary artery disease was diagnosed
      in 22, 15 of whom had increased troponin I values, yielding a sensitivity of 68%
      (48%-84%) and a specificity of 82% (53%-97%). In the subgroup of patients with
      pain lasting > 30 min, sensitivity reached 85% (59%-97%) and specificity 83% (42%
      99%). There were no significant differences between subgroups with different time
      delays from appearance of symptoms to blood extraction. CONCLUSIONS: Cardiac
      troponin I is very useful for the studying ischemic chest pain without a
      definitive diagnostic ECG nor biochemical data, resulting in a high sensitivity
      and specificity for myocardial ischemic injury detection. Its diagnostic value
      increases in cases of prolonged pain episodes.

PMID- 9542436
TI  - [Coronary surgery without extracorporeal circulation: 5-year experience].
AB  - INTRODUCTION: Coronary surgery without extracorporeal circulation is now an
      accepted technique of myocardial revascularization. A progressive increase in
      operations has recently been observed. OBJECTIVE: We report our total experience
      with this technique in a consecutive series of patients operated on since 1991.
      This series is compared with other series of patients who underwent coronary
      surgery using cardiopulmonary bypass. PATIENTS AND METHODS: From December 1991 to
      July 1996, thirty patients underwent myocardial revascularization without
      cardiopulmonary bypass through median sternotomy at our institution. This group
      was retrospectively compared with 22 patients who received isolated coronary
      artery bypass grafting with cardiopulmonary bypass (excluding reoperations)
      during the same period of time. RESULTS: There were two hospital deaths and one
      case of myocardial infarction during the early postoperative period which
      required urgent reintervention. There were two variables showing a statistically
      significant difference between the groups with and without cardiopulmonary
      bypass. Incidence of non-fatal preoperative myocardial infarction increased (53%
      vs 23%), whereas minor mechanical ventilation time was reported (7 +/- 5 vs 14 +/
      9 h) in the group without cardiopulmonary bypass. Follow-up (1 to 55 months
      after operation, mean 29 months) was completed. There were no cardiac-related
      deaths. No return of angina nor any new myocardial infarctions were recorded. New
      myocardial revascularizations were not necessary. CONCLUSIONS: Myocardial
      revascularization without extracorporeal circulation obtained good results that
      were similar to conventional procedures and were cost-effective.

PMID- 9542437
TI  - [Clinical and echocardiographic impact of neonatal aortic valvuloplasty].
AB  - OBJECTIVES: The selection of patients for balloon aortic valvuloplasty is a vital
      clinical challenge in neonatal aortic stenosis. The present study was designed to
      establish possible predicting factors for poor results after balloon therapy.
      PATIENTS AND METHODS: 2D echocardiographic, Doppler color and clinical variables
      (grade of cardiac failure, aortic "anulus", mitral anulus, left ventricular
      diameter, ascending aorta, instantaneous Doppler gradient, and grade of aortic
      regurgitation) were analyzed in 32 neonates submitted to balloon dilation at 22
      +/- 18 days of life. The evaluations were conducted during three periods in
      respect to balloon therapy (A: before; B: immediately after, and C: mid-term
      follow-up). The outcome in both, B and C periods was defined as favorable (all
      survivors with Doppler gradient < or = 70 mmHg and no other intervention on the
      valve) and unfavorable (death, first stage of univentricularization, valvular
      replacement or survivors with Doppler gradient > 70 mmHg). Mean values between
      subgroups were compared by Wilcoxon test; unconditional logistic regression was
      used to analyze the impact of cardiac failure and anatomic variables (continuous,
      categorized or Z) on the outcome. RESULTS: The Doppler gradient decreased from 70
      +/- 28 to 34 +/- 14 mmHg after the valvuloplasty, and no changes were detected in
      the follow-up period (36 +/- 8 mmHg). An immediate favorable result was obtained
      in 72% of the patients; its consisted of 50% in period C. Nine neonates had an
      immediate unfavorable outcome (6 deaths and 3 with Norwood operation). In the
      follow-up, three patients had valvular replacement, one patient Doppler gradient
      > 70 mmHg and one patient with left ventricular endomyocardial abnormalities
      died. The severe cardiac failure (odds ratio: 33; CL 2.4-443; p = 0.008) and all
      categorized anatomic variables (aortic "anulus" < or = 6 mm; mitral anulus < or =
      9 mm; ascending aorta < or = 8 mm; left ventricular diameter < or = 13 mm) were
      related with the immediate poor outcome. At 7.6 years, survival and freedom with
      no valvular replacement nor reintervention probability rates were 83% and 67%,
      respectively. CONCLUSIONS: 2D echo Doppler provides essential information about
      the anatomic and functional lesions coexisting with severe or critical aortic
      stenosis in neonates. Patients with left heart hypoplasia and severe heart
      failure should not be candidates for balloon valvuloplasty. The degree of
      residual aortic regurgitation and endomyocardial abnormalities of the left
      ventricle play an important role in the mid-term follow-up.

PMID- 9542438
TI  - [Heart pathology of extracardiac origin (V). Recent advances in chagasic
      cardiomyopathy].
AB  - INTRODUCTION AND OBJECTIVES: Chronic Chagas' heart disease is an important public
      health problem in Latin America. Rural migration from endemic to nonendemic
      countries has aroused widespread interest (United States, Spain) because of the
      possibility of observing affected patients. METHODS: Review of recent literature.
      RESULTS: The diagnosis of Chagas' cardiomyopathy is based on the triad of
      epidemiological history, positive serology and the clinical Chagas' syndrome.
      About 75% of asymptomatic seropositive subjects had no or almost no heart damage
      but the disease could be transmitted by blood donation. The other 25% may develop
      arrhythmias, heart failure and/or embolisms. Specific parasiticidal drugs are
      mainly used in the acute phase. CONCLUSIONS: In countries where Chagas' disease
      is infrequent, patients may be inadvertently diagnosed as having primary dilated
      or ischemic cardiomyopathy. Disease reactivation in immunodepressed patients due
      to AIDS, chemotherapy for cancer or for organ transplantation constitutes a
      formidable clinical challenge. Sanitary prophylactic measures are the strategies
      of choice.

PMID- 9542439
TI  - [Staphylococcus aureus bacteremia and a mass in the right atrium in a patient
      carrying a central port].
AB  - A male heroin abuser was admitted because of Candida endophthalmitis. A permanent
      central venous line was inserted. Three months later, he had positive catheter
      and blood cultures with Staphylococcus aureus. Transthoracic and transesophageal
      echocardiography and magnetic resonance revealed a right atrial mass. Treatment
      with antibiotics in addition to clinical and echocardiographic follow up was
      decided upon. Six weeks later, a transesophageal echocardiography showed a
      decrease in right atrial mass size and the patient was discharged asymptomatic
      without treatment. Three months later, he was well and a new transesophageal
      echocardiography showed a further decrease in atrial mass size with signs of
      fibrosis. This follow up supports the clinical suspicion of thrombus in the right
      atrium attributable to a central venous line and Staphylococcus aureus
      bacteremia.

PMID- 9542440
TI  - [Minimally invasive surgery of the mitral valve].
AB  - The technique of minimal access for mitral valve operations is commented on. A
      small right mediastinotomy is performed, which is a small right parasternal
      incision with resection of two costal cartilages. A correct exposure of the
      mitral valve is achieved through the right atrium and interatrial septum,
      allowing for adequate surgical correction.

PMID- 9542441
TI  - [Pericardial tamponade and a mass in the pericardial cavity as the first clinical
      manifestation of a pulmonary neoplasms].
AB  - Cardiac tamponade and the finding of a simple pericardial mass as the first
      manifestations of a malignant neoplasia from another location are exceedingly
      rare events. Here we present a patient affected with a lung carcinoma whose first
      clinical manifestation was the development of a cardiac tamponade that
      established itself quickly within the context of a mass inside the pericardial
      cavity and adhered to the left atrium.

PMID- 9542442
TI  - Anticipating rotavirus vaccines: review of epidemiologic studies of rotavirus
      diarrhea in Argentina.
AB  - Rotavirus is the most common cause of severe diarrhea in children worldwide, and
      vaccines currently being field-tested could be available for childhood
      immunization in several years. To assess the rotavirus disease burden in
      Argentina and the value of future national surveillance for the disease, we
      reviewed available data on rotavirus detections reported by published and
      unpublished studies conducted in nine Argentine cities and by a multicenter
      study. Data from these studies indicated that rotavirus was detected in 20% of
      5,226 specimens (within a range of 6% to 54% for different studies) from children
      hospitalized for diarrhea and in 9% of 6,587 specimens (within a range of 5% to
      22% for different studies) from children who were outpatients, members of mixed
      populations (hospitalized patients and outpatients), or survey subjects in
      community-based studies. The hospital data showed that while rotavirus was
      detected throughout the year, a peak occurred during the winter months (May-July)
      when up to half of the children with diarrhea were found positive for rotavirus.
      Attempted serotyping of 294 rotavirus-positive specimens for G-protein by three
      laboratories was successful in 230 cases (78%); the resulting data indicated that
      serotype G1 was the most common (being present in 60% of the successfully
      serotyped specimens), followed by G2 (in 20%), G4 (in 14%), and G3 (in 5%). Based
      on national data for Argentina, we estimate that in 1991 there were roughly
      84,500 rotavirus-associated outpatient visits (1 for every 8 births) and 21,000
      hospitalizations averaging 4 days in length (1 for every 31 births), all of which
      entailed direct medical costs estimated at US$ 27.7 million. These preliminary
      data show that the rotavirus disease burden in Argentine children is extensive
      and could be decreased by a safe and effective vaccine. Further surveillance is
      needed to improve our understanding of the epidemiology and distribution of
      rotavirus strains in Argentina, to more accurately assess the cost-effectiveness
      of a rotavirus vaccine program, and to indicate what methods might best be used
      to monitor such a program's impact.

PMID- 9542443
TI  - [Program for the prevention and control of acute respiratory diseases in infancy
      in Santiago, Chile].
AB  - This paper describes and examines the activities for the prevention and control
      of acute respiratory infections (ARI) carried out by a pediatric program in a
      government health service that provides care to a low-income population in
      Santiago, Chile. The study area has a population of just over one million people
      and is served by one general hospital, 16 primary care clinics, and eight rural
      health posts. Specific activities carried out by the ARI program include
      personnel training as well as control measures at the primary care level and
      hospitalization of children with severe ARI. In the first 5 years of the program
      (1990-1994), a reduction in annual mortality from pneumonia from 3.0 to 1.7 per
      1,000 was observed among children under the age of one year, which contributed to
      a decline in infant mortality from 13.5 to 8.9 deaths per 1,000 live births. In
      1994, program costs amounted to US$ 224,000. Judging from the results obtained,
      the ARI prevention and control program has made a valuable contribution in the
      area of child health.

PMID- 9542444
TI  - [Determination of the dispersion of microorganisms in the course of dental
      surgical activity].
AB  - The professionals and patients involved in dental examinations are at risk for
      infection by various disease-causing bacteria, viruses, and fungi, such as those
      responsible for hepatitis, tuberculosis, herpes, and AIDS. It is known that
      aerosols and spatter containing pathogenic microorganisms can spread during an
      examination. Nevertheless, some dental clinics are designed to have multiple
      examination areas in the same room, with no physical barriers between them. The
      objective of this study was to verify the reach of spatter resulting from the use
      of a triple syringe and high-rotation turbine during five simulated exams in a
      collective clinic, bearing in mind that spatter can contain the patient's saliva
      and blood. To facilitate tracking of the spatter, aniline dye (pink, blue,
      yellow, green, and brown) was added to the water in the appropriate receptacle in
      each of the five units. The room, the equipment, and the patient's and operator's
      clothing were covered with white paper. A high concentration of spatter was
      observed on the chair, the operator, and the floor of each unit, and it also
      appeared on the chairs and trays of the surrounding units. The maximum distance
      reached by spatter was 1.82 m from a point on the chair corresponding to the
      position of the patient's mouth. During real simultaneous examinations, the
      surrounding chairs and their patients and operators, as well as the trays
      containing sterilized instruments, are within spatter range. Therefore, there is
      a real possibility of cross-infection, and physical barriers should be placed
      between the units. This study also confirmed the need for protection of the
      operator's face, body, hair, and arms, since these regions were heavily affected
      by spatter.

PMID- 9542445
TI  - [Data on birthweight in developing countries: are surveys useful?].
AB  - The main source of data on birth weight in developing countries is statistics
      from health facilities, although most developing countries do not produce annual
      estimates of the incidence of low birth weight from these data. Such estimates
      would be subject to selection bias as the data are usually limited to babies born
      within health facilities, and therefore are representative of a subgroup that is
      markedly different from the overall population of neonates. Since 1990 the
      Demographic and Health Surveys programme has included questions on recalled birth
      weight and relative size at birth in 15 national surveys. In this article, we
      show that these cross-sectional surveys can provide a useful data source for
      making national estimates of mean birth weight and the incidence of low birth
      weight. The extent of misclassification of birth weight is, however, too large to
      use the data on relative size as birth as an indicator of low birth weight at the
      individual level.

PMID- 9542446
TI  - [Epidemic outbreak of Salmonella richmond infection in Castellon, Spain].
AB  - A case-control study was carried out to investigate an outbreak of acute
      gastroenteritis among a military detachment stationed in a rural area of
      Castellon, Espana. The purpose of the study was to determine the causes of the
      outbreak and develop control measures. Of the 153 men in the detachment, 135 were
      included in the study. Between 9 and 11 August 1993, 45 cases were reported; the
      patients' average age was 19.2 +/- 1.5 years. The attack rate was 33.3%. The
      clinical picture was dominated by the following symptoms: diarrhea (76%),
      vomiting (67%), nausea (67%), and abdominal pain (28%). The median duration of
      symptoms was one day, and that of the incubation period was 33 hours. Only one
      patient required hospitalization and all of them recovered. Salmonella richmond
      (6.7: and :1.2) was isolated in 5 of the 14 stool cultures performed. An
      association was also discovered between the illness and consumption of water from
      an aqueduct that flowed near the camp. A logistic regression model showed that
      consumption of water from this source remained associated with cases after
      adjusting for age and the consumption of various foods (odds ratio = 96.5; 95%
      confidence interval, 11.4-814.4). The risk of suffering from the illness rose
      with the amount of water consumed (chi 2 trend test = 65.4, P < 0.0001). Chemical
      and bacteriological analyses of the aqueduct water indicated the presence of
      fecal contamination. The aqueduct had not been subject to sanitary monitoring,
      even though the water was used to irrigate agricultural crops. The widespread
      presence in the environment of species of Salmonella was demonstrated. Health
      education and microbiological studies of water courses can be of great value in
      preventing such epidemics.

PMID- 9542447
TI  - Technologic organization of malaria control in Sao Paulo, Brazil, 1930-1990.
AB  - Since the 1970s, when the world seemed on the threshold of malaria eradication,
      the incidence of the disease has increased in several countries. The upturn in
      cases raised a series of questions, and for some time malariologists and public
      health authorities scarcely understood what was happening. In an attempt to
      better comprehend the process, this article reviews the frequency of malaria
      cases in Sao Paulo, Brazil, between 1930 and 1990, examining the following
      factors in each of three 20-year time periods: the importance of malaria in the
      society, the conditions under which the disease occurred, the epidemiologic
      knowledge of the time, the technical instruments available to fight it, and the
      control strategies that were used. Through the construction of technological
      models based on these factors, it became clear that the occurrence of the
      disease, knowledge about it, and, consequently, the ways it was dealt with
      changed over time. In light of this research, the article discusses current
      options for the control of malaria.

PMID- 9542448
TI  - [Efficiency of oxidant gas generator cells powered by electric or solar energy].
AB  - Diseases caused by microbial contaminants in drinking water continue to be a
      serious problem in countries like Mexico. Chlorination, using chlorine gas or
      chlorine compounds, is one of the best ways to treat drinking water. However,
      difficulties in handling chlorine gas and the inefficiency of hypochlorite
      solution dosing systems--due to sociopolitical, economic, and cultural factors-
      have reduced the utility of these chlorination procedures, especially in far
      flung and inaccessible rural communities. These problems led to the development
      of appropriate technologies for the disinfection of water by means of the on-site
      generation of mixed oxidant gases (chlorine and ozone). This system, called
      MOGGOD, operates through the electrolysis of a common salt solution. Simulated
      system evaluation using a hydraulic model allowed partial and total costs to be
      calculated. When powered by electrical energy from the community power grid, the
      system had an efficiency of 90%, and in 10 hours it was able to generate enough
      gases to disinfect about 200 m3 of water at a cost of approximately N$8 (US
      $1.30). When the electrolytic cell was run on energy supplied through a
      photoelectric cell, the investment costs were higher. A system fed by
      photovoltaic cells could be justified in isolated communities that lack
      electricity but have a gravity-fed water distribution system.

PMID- 9542449
TI  - Tobacco use among Cuban migrants at Guantanamo Bay, Cuba.

PMID- 9542450
TI  - [Public health services: response to demands or needs?].

PMID- 9542451
TI  - Evaluation of a novel drinking water treatment and storage intervention in
      Nicaragua.

PMID- 9542452
TI  - [The cataract, an unavoidable sign manifestation of aging?].

PMID- 9542453
TI  - [Inline skating, an old sport, newly discovered: harmless or a potential danger
      with socioeconomic effects?].
AB  - Over a period of one year, all accidents associated with in-line skating (ILS)
      were surveyed. Sport-specific data was recorded with a standardized
      questionnaire. The study comprised 66 patients with 75 injuries (48 upper limb,
      16 skull, eight lower limb, three trunk). We were looking after 42 male and 24
      female patients with an average age of 20 years (5-53 years). Twenty-seven
      patients (40%) had to be treated as inpatients. Overall, the most frequent injury
      (one third of all injuries) was forearm fracture close to the wrist (21 radius
      fractures, four radioulnar fractures). It had to be reset in 20 cases. Additional
      internal fixation was required in 10 cases (Kirschner wire osteosynthesis,
      intramedullary nailing or plate osteosynthesis). Only five patients could be
      treated with plaster cast fixation alone. Most patients with injuries in the
      vicinity of the wrist were not wearing a wrist protector at the time of the
      accident. The most frequent reasons given for not wearing protectors was
      forgetfulness or the high price of protectors. However, there were also two
      distal radius fractures and a disc injury in the wrist in patients who had been
      wearing wrist protectors. In most cases, ILS accidents lead to appreciable damage
      requiring a healing period of several weeks to months (average period of loss of
      work 41 days). The bfu (advisory center for accident prevention) reckons with
      60,000 ILS cases annually in Switzerland. These injuries are thus of great
      socioeconomic importance. In the future, better risk behavior must be achieved by
      informing the population (wearing protectors, especially for the wrist and head,
      attendance of training courses).

PMID- 9542454
TI  - [Depression as a psychophysical illness phenomenon].
AB  - The old Greeks understood depression as a somatic process as well as an
      oppressing experience. Disturbances of the transmitters, ligands and receptors
      and the decoupling of the feedback-systems of the hypothalamic-pituitary
      adrenocortical systems with an impairment of the immune-system are experienced as
      depression with its narcissistic depletion and orientation towards conscience and
      order. Thereby the conscious experience is less differentiated than the complex
      somatic processes which are proving it. Under a holistic aspect it is, however,
      doubtful whether psychotherapy can be differentiated from somatotherapy. Each
      psychotherapy acts through the sensory organs on the body like somatotherapy.
      Until now, however, only a few results of research are known concerning somatic
      parameters, for example of the transmitter- and immune-processes of the body,
      during a simple, with preference cognitive-behavioral psychotherapy. For that the
      researchers would have to be trained to reach a reliable evaluation of its
      somatic parameters. As it was proved scientifically, the influence onto somatic
      functions is even possible with complex psychotherapeutic methods such as
      hypnosis. Such research is until now still relatively seldom done. This may be
      due, on one hand, to the fact that many psychiatrists and other physicians still
      maintain the fatal psychophysical dualism and on the other hand, that the
      pharmaceutical industry has until now not had an interest in comparative
      investigations concerning the effects of psychotherapy and pharmacotherapy.

PMID- 9542455
TI  - [New developments in asthma therapy: how do individual leukotriene antagonists
      work?].
AB  - Today it is generally acknowledged that bronchial asthma is a chronic
      inflammatory airway disease which is marked by recurrent bronchial obstructions
      and hyperreactivity of the airways. The best anti-inflammatory characteristics
      are shown by corticosteroids. However these can have considerable side-effects in
      long-term, systemic use. The search for alternative forms of therapy has for some
      time concentrated on the development and testing of leukotriene antagonists.
      These can limit the effect of leukotrienes via receptor antagonism or synthesis
      inhibition. The leukotrienes B4, C4, and D4 count as important key mediators in
      bronchial asthma. They are released by numerous inflammatory cells, have a
      bronchoconstricting effect and chemotactic characteristics, promote vessel
      permeability and increase mucous secretion. In addition, they probably increase
      bronchial hyperreactivity. Among biosynthesis restrictors, the 5-lipoxygenase
      restrictors have shown an anti-inflammatory effect in both experimental asthma
      models and in clinical use. In mild to moderate asthma, lung function improved
      and the use of a concomitant beta-agonist medication was reduced. While the older
      leukotriene receptor antagonists were rather disappointing, the newer substances
      display a significantly improved effect, are generally well tolerated and can
      also be given orally. In experimental asthma models, receptor antagonists, after
      antigen provocation, led to a marked reduction in bronchoconstriction and a
      decrease in the number of inflammatory cells (lymphocytes and eosinophils) in
      bronchial alveolar fluid. In clinical studies, this new class of drugs showed a
      reduction in clinical symptoms and an improvement in lung function in mild to
      moderate asthma. In addition, a bronchodilatatory effect was shown. The option of
      oral administration and good tolerance should improve compliance. The potential
      and long-term efficacy in severe asthma remains unclear. Further studies are
      required to elucidate the scope of their role and define their place in the
      treatment of asthma.

PMID- 9542456
TI  - [Dealing with the scientific literature--a report of experiences].
AB  - There are several problems in collecting, analysing and receiving medical
      articles or literature. The increasing number of medical articles calls for a
      computer-aided system for literature data base programs. Therefore we want to
      present our own experiences. The computer-aided data bases such as MEDLINE and
      EMBASE are very useful but many other difficulties regarding citation and
      procurement of articles remain.

PMID- 9542457
TI  - [Obstructive sleep apnea, treatment with CPAP and health risks].

PMID- 9542458
TI  - [Fever, headache and weakness. Primary cytomegalovirus infection].
AB  - We report on an acute primary infection with cytomegalo virus in a 26 year old
      immunocompetent and hitherto healthy man. The course of the disease was
      characterized by prolonged febrile state, headaches, myalgias and markedly
      reduced general condition. Indicators leading to diagnosis were in view of
      otherwise unremarkable clinical findings, reactive lymphocytosis, mild
      splenomegaly as well as elevated transaminases interpreted as concomitant
      hepatitis. The evolution was benign under symptomatic treatment. The patient
      recovered rapidly and completely. The clinical picture of primary CMV infection
      in nonimmunosuppressed adults is discussed.

PMID- 9542459
TI  - [Sarcoidosis and subclinical hyperthyroidism].

PMID- 9542460
TI  - Surveillance of tuberculosis in the WHO European Region in 1995. Results of a
      feasibility study.

PMID- 9542461
TI  - Global Programme for Vaccines and Immunization (GPV). The WHO position paper on
      Haemophilus influenzae type b conjugate vaccines.

PMID- 9542462
TI  - Dracunculiasis. Certification of transmission-free status.

PMID- 9542463
TI  - National Leadership Conference on Physical Activity and Women's Health.

PMID- 9542464
TI  - The role of physical activity in minority populations.

PMID- 9542465
TI  - Tailoring interventions to promote physically active lifestyles in women.

PMID- 9542467
TI  - Principles and practice of women's health care.

PMID- 9542466
TI  - Correlates of intention to use the female condom among women taking methadone.

PMID- 9542468
TI  - Society of Cardiovascular Anesthesiologists 20th annual meeting. Seattle,
      Washington, USA. April 25-29, 1998. Abstracts.

PMID- 9542469
TI  - Experiences with recombinant factor VIII products: development of inhibitors and
      immune tolerance therapy.

PMID- 9542470
TI  - 42nd Annual meeting of the GTH (Gesellschaft fur Thrombose- und
      Hamostaseforschung). Frankfurt am Main, Germany, February 25-28, 1998. Abstracts.

PMID- 9542471
TI  - Clinical pharmacology in an aging population.

PMID- 9542472
TI  - Protein binding of aspirin and salicylate measured by in vivo ultrafiltration.
AB  - OBJECTIVE: Methods for measuring protein binding of drugs generally require
      direct measurement of the concentration of unbound drug and thus may require a
      highly sensitive assay. In vivo ultrafiltration has been used to determine
      protein binding of endogenous substances. We have examined its value for
      measuring protein binding of drugs because it requires measurement of only the
      concentration of total drug, not unbound drug, in plasma. METHODS: The protein
      binding of aspirin and its metabolite salicylate was measured in 29 healthy
      subjects 20 minutes after a single oral dose of 600 mg soluble aspirin, by the
      new method, in vivo ultrafiltration, as well as by a standard method, in vitro
      ultracentrifugation. RESULTS: The data for salicylate were examined
      systematically to determine the optimal method of determining estimates of
      protein binding by in vivo ultrafiltration. Estimates of protein binding of
      salicylate were 81.7% +/- 10.1% (mean +/- SD) by the in vivo method and 81.6% +/-
      11.3% by in vitro ultracentrifugation. Bland-Altman analysis of agreement showed
      that within-individual differences in percentage of protein binding determined by
      the two methods did not differ significantly from zero (mean difference, 0.07%;
      95% confidence interval, -2.33 to +2.46). There was a highly significant
      correlation between estimates of protein binding by the two methods (r = 0.82; p
      = 0.001). Protein binding of aspirin was estimated of protein binding by the two
      methods (r = 0.82; p = 0.001). Protein binding of aspirin was estimated at 58.3%
      +/- 9.6% by in vivo ultrafiltration and could not be estimated by in vitro
      ultracentrifugation because the concentration of unbound aspirin in plasma was
      below the limit of detection for the assay. CONCLUSION: In vivo ultrafiltration
      can be used to measure protein binding of drugs and has potential advantages over
      conventional methods. A sensitive assay may not be required because the unbound
      drug need not be measured, measurement in vivo may maintain more physiologic
      conditions, and it may be useful in measuring protein binding of drugs that are
      degraded rapidly in vitro.

PMID- 9542473
TI  - Induction of CYP2E1 activity in liver transplant patients as measured by
      chlorzoxazone 6-hydroxylation.
AB  - OBJECTIVE: To examine the phenotypic expression of CYP2E1 in liver transplant
      patients, as measured by the in vivo probe chlorzoxazone, and to evaluate CYP2E1
      activity over time after transplantation. METHODS: Thirty-three stable liver
      transplant patients were given 250 mg chlorzoxazone within 1 year after
      transplantation as part of a multiprobe CYP cocktail; urine and blood were
      collected for 8 hours. Chlorzoxazone and 6-hydroxychlorzoxazone concentrations
      were determined by HPLC. Twenty-eight healthy control subjects, eight patients
      with moderate to severe liver disease, and four patients who had not received
      liver transplants were also studied for comparison. The chlorzoxazone metabolic
      ratio, calculated as the plasma concentration of 6
      hydroxychlorzoxazone/chlorzoxazone at 4 hours after chlorzoxazone administration,
      was used as the phenotypic index. In a subgroup of patients and control subjects,
      additional blood samples were obtained to allow for the calculation of
      chlorzoxazone pharmacokinetic parameters by noncompartmental methods. RESULTS:
      The chlorzoxazone metabolic ratio for the liver transplant patients in the first
      month after transplantation (mean +/- SD, 6.4 +/- 5.1) was significantly higher
      than that after 1 month after surgery (2.1 +/- 2.0), when the chlorzoxazone
      metabolic ratio was not different from control subjects (0.8 +/- 0.5). The
      chlorzoxazone metabolic ratios in the patients who had not received liver
      transplants (1.1 +/- 0.7) were equivalent to those of healthy control subjects.
      The maximum observed 6-hydroxychlorzoxazone plasma concentration was 3046 +/-
      1848 ng/ml in seven liver transplant patients in the first month after surgery
      compared with 1618 +/- 320 ng/ml in 16 healthy control subjects (p < 0.05). The
      maximum observed concentration of chlorzoxazone, the chlorzoxazone apparent oral
      clearance, and the formation clearance of 6-hydroxychlorzoxazone were also
      significantly different between the groups. CONCLUSIONS: We conclude that
      significant induction of CYP2E1, as indicated by the chlorzoxazone metabolic
      ratio, occurs in the first month after surgery in liver transplant patients and
      that drugs that are substrates for CYP2E1 may require dosage alteration during
      that period. Contrary to expectations, drug metabolism is not uniformly depressed
      after liver transplantation.

PMID- 9542474
TI  - Passive versus electrotransport-facilitated transdermal absorption of ketorolac.
AB  - OBJECTIVE: To investigate the bioavailability (extent and rate of absorption) of
      ketorolac from two cutaneous absorption sources, active electrotransport and
      passive transdermal, and to examine the enantiomeric selectivity of
      bioavailability for each source. METHODS: Based on a crossover study in 12
      healthy volunteers, the extent and rate of absorption of ketorolac, delivered by
      a patch, were found by estimating the input rate function of the drug. For that
      purpose, deconvolution was used in two steps. First, intravenous data were
      analyzed to estimate the ketorolac disposition function, and second, postpatch
      data were deconvolved to estimate the unknown patch input profile given the
      disposition function estimated in the first step. Because the input rate function
      curves to be estimated for the patches may be of arbitrary shape, a spline was
      used to model the patch input function, whereas intravenous data were modeled
      with use of a sum of exponentials. Differences in the extent of absorption (F)
      for the four treatment-enantiomer combinations were further examined with a mixed
      effect regression model, based on the sets of four individual estimates of
      bioavailability. RESULTS: On average, the F value for the active electrotransport
      treatment, which exhibited the faster absorption rate, was four times greater
      than the F for the passive transdermal treatment. Further, during the passive
      treatment, R-ketorolac yielded an average F that is 42% greater than that for S
      ketorolac and also exhibited a smaller absorption lag-time. During the active
      treatment, there was no important enantiomeric difference in either extent or
      rate of absorption.

PMID- 9542475
TI  - Effects of erythromycin or rifampin on losartan pharmacokinetics in healthy
      volunteers.
AB  - BACKGROUND: Losartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite,
      E3174, which has greater antihypertensive activity than the parent compound.
      Coadministered drugs that inhibit or induce metabolic processes may therefore
      alter the pharmacokinetics and pharmacologic response of losartan and E3174.
      OBJECTIVE AND METHODS: Ten healthy volunteers were studied to assess the effects
      of CYP3A4 inhibition and nonspecific P450 enzyme induction on the
      pharmacokinetics of losartan and E3174. Subjects completed three 1-week phases
      separated by 6 days: 50 mg losartan every morning, losartan plus 500 mg
      erythromycin four times a day, and losartan plus 300 mg rifampin (INN,
      rifampicin) twice a day. On the eighth day of each phase, serial plasma
      concentrations of losartan and E3174 were obtained over 32 hours and steady-state
      pharmacokinetics were determined. RESULTS: Rifampin decreased the area under the
      concentration-time curve from time zero to 24 hours after the dose (AUC[0-24]) of
      losartan by 35% (349 +/- 246 versus 225 +/- 130; p = 0.0001) and decreased the
      AUC(0-24) of E3174 by 40% (1336 +/- 445 versus 792 +/- 302; p < 0.005). Losartan
      oral clearance was increased by 44% (p = 0.0001). The half-life values of both
      compounds were decreased by 50% (p < 0.005). In contrast, erythromycin did not
      significantly affect the AUC(0-24) or half-life of either losartan or E3174.
      CONCLUSIONS: Rifampin is a potent inducer of losartan and E3174 elimination.
      Given the magnitude of the effect, this interaction is likely to be clinically
      significant. On the basis of the minimal inhibitory effects observed with
      erythromycin, CYP3A4 appears to play a minor role in the in vivo metabolism of
      losartan to E3174. Further studies are needed to define the contribution of other
      isozymes, particularly CYP2C9, to the pharmacokinetics of losartan and E3174.

PMID- 9542476
TI  - Pharmacokinetics and pharmacodynamics of single and multiple oral doses of a
      novel 5-lipoxygenase inhibitor (ABT-761) in healthy volunteers.
AB  - OBJECTIVE: This study evaluated the safety, pharmacokinetics and pharmacodynamics
      of ABT-761 [R(+)-N-[3-[5-(4-fluorophenylmethyl)-2-thienyl]-1- methyl-2-propynyl]
      N-hydroxyurea], a new N-hydroxyurea analog. METHODS: This was a randomized,
      double-blind, placebo-controlled, single- and multiple-dose (15-day) study of ABT
      761 (50 to 200 mg/day) in healthy, nonsmoking adult male volunteers. The
      pharmacokinetics were evaluated by investigation of the time- and dose-dependent
      effects of ABT-761, and the pharmacologic selectivity of ABT-761 was evaluated
      based on calcium ionophore-stimulated leukotriene B4 (LTB4) and thromboxane B2
      (TXB2) biosynthesis ex vivo in whole blood. RESULTS: After single and multiple
      doses, mean observed time to reach maximum concentration values of ABT-761 ranged
      from 4.0 to 7.5 hours. Mean values for maximum concentration and area under the
      plasma concentration-time curve from 0 to 24 hours increased approximately
      linearly with dose. Mean terminal half-life and apparent volume of distribution
      during the terminal elimination phase of ABT-761 ranged from 15.4 to 17.8 hours
      and 69.5 to 78.9 L, respectively, and was dose independent. Steady state was
      reached on day 11 after multiple dosing. Less than 0.05% of unchanged ABT-761 was
      recovered in urine within the 24-hour period after day 15 dosing. Population ABT
      761 plasma concentration at which 50% of the maximum possible inhibition was
      observed for LTB4 inhibition was 0.24 microgram/ml. No differences in mean TXB2
      inhibition were observed between the subjects receiving ABT-761 and placebo.
      CONCLUSIONS: These results indicate that ABT-761 is a potent and selective
      inhibitor of 5-lipoxygenase and the pharmacokinetics of ABT-761 are time and dose
      independent between 50 and 200 mg/day after single and multiple dosing.

PMID- 9542477
TI  - Simvastatin but not pravastatin is very susceptible to interaction with the
      CYP3A4 inhibitor itraconazole.
AB  - BACKGROUND: Itraconazole increases the risk of skeletal muscle toxicity of some 3
      hydroxy-3-methylglutaryl coenzyme A' (HMG-CoA) reductase inhibitors by increasing
      their serum concentrations. We studied possible interactions of itraconazole with
      simvastatin and pravastatin. METHODS: Two randomized, double-blind, two-phase
      crossover studies were performed with use of an identical design, one with
      simvastatin (study I) and one with pravastatin (study II). In both studies, 10
      healthy volunteers received either 200 mg itraconazole or placebo orally once a
      day for 4 days. On day 4, each subject ingested a single 40 mg dose of
      simvastatin (study I) or pravastatin (study II). Serum concentrations of
      simvastatin, simvastatin acid, pravastatin, HMG-CoA reductase inhibitors,
      itraconazole, and hydroxyitraconazole were determined. RESULTS: In study I,
      itraconazole increased the peak serum concentrations (Cmax) and the areas under
      the serum concentration-time curve [AUC(0-infinity)] of simvastatin and
      simvastatin acid at least tenfold (p < 0.001). The Cmax and AUC(0-infinity) of
      total simvastatin acid (naive simvastatin acid plus that derived by hydrolysis of
      the lactone) were increased 17-fold and 19-fold (p < 0.001), respectively, and
      the half-life (t1/2) was increased by 25% (p < 0.05). The AUC(0-infinity) of HMG
      CoA reductase inhibitors was increased fivefold (p < 0.001) and the Cmax and t1/2
      were increased threefold (p < 0.001). In study II, itraconazole slightly
      increased the AUC(0-infinity) and Cmax of pravastatin, but the changes were
      statistically nonsignificant (p = 0.052 and 0.172, respectively). The t1/2 was
      not altered. The AUC(0-infinity) and Cmax of HMG-CoA reductase inhibitors were
      increased less than twofold (p < 0.05 and p = 0.063, respectively) by
      itraconazole. There were no differences in the serum concentrations of
      itraconazole and hydroxyitraconazole between studies I and II. CONCLUSIONS:
      Itraconazole greatly increased serum concentrations of simvastatin, simvastatin
      acid, and HMG CoA reductase inhibitors, probably by inhibiting CYP3A-mediated
      metabolism, but it had only a minor effect on pravastatin. Concomitant use of
      potent inhibitors of CYP3A with simvastatin should be avoided or its dosage
      should be greatly reduced.

PMID- 9542478
TI  - The pharmacodynamics and pharmacokinetics of the 5HT1B/1D-agonist zolmitriptan in
      healthy young and elderly men and women.
AB  - OBJECTIVE: Zolmitriptan is a selective 5HT1B/1D-agonist for the treatment of
      migraine. In this study we investigated the cardiovascular and central nervous
      system effects and the pharmacokinetics of zolmitriptan in young and elderly
      adults. METHODS: Twelve young adult and 12 elderly volunteers received single
      doses of 5, 10, and 15 mg zolmitriptan during a randomized, double-blind, placebo
      controlled study. Blood pressure, heart rate, ECG, and central nervous system
      effects were monitored, and pharmacokinetic parameters of zolmitriptan and its
      metabolites calculated. RESULTS: Zolmitriptan did not affect heart rate and had
      little effect on systolic blood pressure in the young adults. In the elderly,
      mean peak supine systolic blood pressure values were 9 to 16 mm Hg higher after
      zolmitriptan than after placebo. Mean peak diastolic pressure was 6 to 10 mm Hg
      higher in both age groups. These changes were transient. Postural changes in
      blood pressure were unaffected. There was a dose-related increase in sedation,
      but the magnitude of the effects was small. Mean observed peak plasma
      concentration (Cmax) and area under the plasma concentration-time profile [AUC(0
      infinity)] for zolmitriptan and its active N-desmethyl metabolite were similar in
      both age groups but higher in young women than in young men. Metabolite/parent
      ratios probably the result of greater first-pass metabolism in young men.
      Zolmitriptan half-life was 2.8 to 3.6 hours in the elderly compared with 2.7 to
      2.9 hours in young adults. Mean Cmax and AUC(0-infinity) for the inactive, N
      oxide, and the indole acetic acid metabolites were higher in the elderly,
      associated with lower renal clearance. CONCLUSIONS: Zolmitriptan was well
      tolerated, with an effect of age on its effects on blood pressure and the
      pharmacokinetics of its metabolites. The data suggest no need for dose adjustment
      for age. In young subjects, concentrations were higher in women than in men, but
      the differences were insufficient to justify dosage adjustment.

PMID- 9542479
TI  - Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of
      steroid 5 alpha-reductase, in healthy volunteers.
AB  - The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor
      of steroid 5 alpha-reductase, were investigated in healthy volunteers, with use
      of plasma FK143 concentrations and serum dihydrotestosterone levels as an index
      for pharmacologic effects. The area under the plasma concentration-time curve
      from zero to infinity [AUC(0-infinity)] and maximum plasma concentration [Cmax]
      were increased dose proportionally after oral administration (100 to 500 mg)
      while subjects were in the fed state. The AUC(0-infinity) and Cmax after 500 mg
      oral administration during fed conditions were significantly larger than those
      during the fasted state, suggesting an increase of the absorption of FK143.
      Dihydrotestosterone concentrations after a single administration of FK143 (100 to
      500 mg) during fed conditions decreased to about 65% of predose values and
      thereafter slowly recovered to the same levels as predose values at 168 hours. A
      combined pharmacokinetic-pharmacodynamic model was constructed with use of
      changes in dihydrotestosterone concentrations. The pharmacokinetic
      pharmacodynamic profiles of FK143 after repeated administration were predictable
      with use of the pharmacokinetic-pharmacodynamic parameters obtained after a
      single administration of FK143.

PMID- 9542480
TI  - A pharmacokinetic interaction study of avitriptan and propranolol.
AB  - OBJECTIVE: To assess whether a clinically significant change in the
      pharmacokinetics of avitriptan and propranolol is observed in healthy subjects
      after coadministration of the two drugs. METHODS: The pharmacokinetics of
      avitriptan and propranolol were investigated when the two drugs administered
      separately and when two 150 mg doses of avitriptan 2 hours apart were added to a
      steady-state regimen (80 mg twice a day) of propranolol. The pharmacokinetics of
      metabolites of avitriptan (N-desmethylavitriptan, methoxypyrimidinyl piperazine,
      and O-desmethylavitriptan) and the pharmacokinetics of 4-hydroxypropranolol were
      also assessed. RESULTS: Administration of avitriptan alone and together with
      propranolol resulted in small increases in mean blood pressure and small
      decreases in heart rate. Administration of propranolol resulted in lowering of
      blood pressure and heart rate consistent with the beta-blocking actions of
      propranolol. There were no changes in the pharmacokinetics of avitriptan after
      coadministration with propranolol. However, area under the plasma concentration
      time curve (AUC) of propranolol showed a 20% increase after coadministration with
      avitriptan, whereas the AUC of 4-hydroxypropranolol significantly decreased.
      Avitriptan therefore appeared to affect the metabolism of propranolol to 4
      hydroxypropranolol. The peak plasma concentration and AUC for N
      desmethylavitriptan and the AUC for methoxypyrimidinyl piperazine also showed
      statistically significant increases (about 25%) when avitriptan was
      coadministered with propranolol. CONCLUSIONS: Considering the wide safety margin
      of propranolol, the increase in the exposure is not clinically significant. The
      increase in the exposure to the metabolites of avitriptan is also not considered
      to be clinically significant because the metabolite contribution to the
      pharmacologic activity or side effects is expected to be minimal. Based on these
      findings, avitriptan may be added to a steady-state regimen of propranolol as an
      abortive antimigraine therapy.

PMID- 9542481
TI  - Dose-related effects of oral acetaminophen on cold-induced pain: a double-blind,
      randomized, placebo-controlled trial.
AB  - The cold-pressor test is a widely used pain-induction model in humans. This
      method has been shown to be a sensitive measure for detecting opioid analgesia.
      However, nonsteroidal anti-inflammatory drugs have not produced consistent
      analgesic effects with use of this model. The analgesic effect of acetaminophen
      (INN, paracetamol) on cold pressor-induced pain has not been reported by other
      investigators. In this study, a double-blind, randomized, placebo-controlled
      design was used to evaluate the dose-related effects of oral acetaminophen on
      cold pressor-induced pain in 18 normal healthy human subjects. We observed dose
      related analgesic activity of oral acetaminophen using the cold pressor-induced
      pain model in these subjects. There were statistically significant main effects
      of both dose and time (pain and bothersomeness ratings decreased with increasing
      drug dose and increased over time). In pairwise comparisons only the contrast
      between the highest dose of acetaminophen (1000 mg) and placebo reached
      statistical significance. Results from our study suggest that the cold-pressor
      method may have clinical value in evaluating nonopioid analgesic agents.

PMID- 9542482
TI  - Pharmacodynamics and pharmacokinetics of DMP 728, a platelet GPIIb/IIIa
      antagonist, in healthy subjects.
AB  - DMP 728 showed a dose-dependent inhibition of platelet aggregation at doses of
      0.05 to 0.9 mg per subject, with a maximal inhibition (> 90%) of platelet
      aggregation at doses of 0.9 mg per subject and higher. Minimal changes in
      bleeding time from baseline were observed at doses up to 0.6 mg per subject. At
      the 0.9 mg/subject dose level, bleeding time was prolonged by approximately
      twofold to threefold above the baseline. At higher doses (1.5 mg/subject to 3.9
      mg/subject), bleeding time prolongation was > 30 minutes during the infusion. In
      all dose groups, bleeding times returned to the control value within 8 hours
      after cessation of the infusion. Maximum plasma concentration and area under the
      curve of DMP 728 increased linearly and proportionally to the dose. No clinical
      changes in vital signs, 12-lead electrocardiograms, physical examinations,
      coagulation tests, or stool hemoccult tests were observed at any of the doses. In
      conclusion, DMP 728 is a potent antiplatelet agent and well tolerated at doses
      ranging from 0.05 to 3.0 mg/subject.

PMID- 9542483
TI  - Gestational diabetes mellitus--are African diagnostic criteria warranted?

PMID- 9542484
TI  - Does successful completion of the Perinatal Education Programme result in
      improved obstetric practice?
AB  - OBJECTIVE: To determine whether successful completion of the Perinatal Education
      Programme (PEP) improves obstetric practice. METHOD: The three midwife obstetric
      units (MOUs) in a health district of Mpumalanga were included in the study. Two
      MOUs enrolled in the PEP and the third did not. A 'before-and-after' study design
      was used to assess any changes in practice, and to monitor whether any changes
      occurred in the district during the time of the study; data were also collected
      at the third MOU. Data were collected by scoring of the obstetric files after the
      patient had delivered. OUTCOME MEASURES: We ascertained whether the obstetric
      history, syphilis testing, blood group testing, haemoglobin measurement and
      uterine growth assessment were performed during antenatal care along with whether
      appropriate action was taken. For intrapartum care, estimation of fetal weight,
      the performance of pelvimetry, blood pressure monitoring, urine testing,
      evaluation of head above pelvis, fetal heart rate monitoring, monitoring of
      contractions and plotting of cervical dilatation, and whether the appropriate
      actions were taken, were assessed. RESULTS: Eight of the 13 midwives at the two
      MOUs completed the PEP and all demonstrated an improvement in knowledge. Case
      notes of 303 patients from the various clinics were studied. There was no change
      in the referral patterns of any of the clinics during the study period. The
      obstetric history was well documented, but in no group was there a satisfactory
      response to a detected problem; appropriate action was taken in between 0% and
      12% of cases. Syphilis testing was performed in 56-82% of cases, with no
      difference between the groups. The haemoglobin level was measured in only 4-15%
      of patients, with no difference before or after completion of the PEP. Where a
      problem in uterine growth was detected, an appropriate response occurred in 0-8%
      of patients and no difference before or after completion of the PEP was
      ascertained. In all groups, estimation of fetal weight and pelvimetry were seldom
      performed, the urine and fetal heart rate documentation were moderately well done
      and the blood pressure monitoring, assessment of head above pelvis, monitoring of
      contractions and plotting of cervical dilatation were usually performed. No
      differences before or after the PEP were detected. Where problems were detected,
      appropriate actions taken during labour improved, but not significantly.
      CONCLUSION: Completion of the obstetric manual of the PEP improved the knowledge
      of the midwives but no alteration in practice was detected.

PMID- 9542485
TI  - Comparison of the footpump suction evacuator with the manual vacuum aspirator for
      uterine evacuation.
AB  - OBJECTIVE: To compare the efficacy of a novel footpump suction evacuator with the
      manual vacuum aspirator in the management of women with incomplete abortions
      requiring uterine evacuation. DESIGN: A prospective comparative analysis of women
      allocated to either manual vacuum aspiration of the uterus or footpump suction
      evacuation, following first- or second-trimester incomplete abortion. SETTING:
      The gynaecology casualty theatre, Groote Schuur Hospital, Cape Town. PATIENTS:
      121 women with first- or second-trimester abortions. Patients with signs of
      septic abortion were excluded from the study. INTERVENTIONS: Uterine evacuation
      under general anaesthesia by means of a manual vacuum aspirator or a novel
      footpump suction evacuator. OUTCOME MEASURES: Endpoints assessed included
      duration of the procedures, ease of evacuation, estimated blood loss, volume of
      products of conception obtained, postoperative complications of the procedures
      and amount of analgesia required postoperatively. RESULTS: The manual vacuum
      aspirator and footpump suction evacuator appeared equally effective for uterine
      evacuation. There were no significant differences in the endpoints assessed.
      CONCLUSIONS: Both methods appear equally effective for uterine evacuation.

PMID- 9542486
TI  - Unbooked mothers and their babies--what causes the poor outcomes?
AB  - OBJECTIVES: To compare perinatal outcome between booked and unbooked mothers of
      similar gestational age using birth weight as a proxy for gestational age.
      DESIGN: 91 unbooked mothers were obtained from a pool of 2,054 mothers from the
      Chiawelo district in Soweto delivered consecutively at the local community clinic
      or at Baragwanath, the referral hospital. For each of these, a single booked
      control from the same pool was found, matched to within 50 g birth weight.
      Detailed information from case notes was used to compare the two groups and their
      perinatal outcomes. RESULTS: Unbooked mothers tended to be at lower obstetric
      risk. None of the unbooked versus 10 of the booked mothers had a poor obstetric
      history (2 previous abortions or a previous perinatal death). There was a trend
      to more twin pregnancies (5 v. 1) and more previous caesarean sections (12 v. 8)
      in the booked mothers. Perinatal mortality rates were not significantly different
      (unbooked 258/1,000; booked 268/1,000). Perinatal morbidity, as assessed on the
      basis of need for neonatal admission and ventilation, was similar in the two
      groups. CONCLUSION: Booked mothers were at higher risk, with worse obstetric
      histories, which probably influenced their decisions to book for antenatal care.
      Unbooked mothers seemed to be at lower risk, often presenting 'unbooked' because
      of preterm complications. Many of the latter would probably have booked had their
      pregnancies advanced uneventfully. As such, unbooked status should not be
      regarded as a high-risk, poor prognostic category. These mothers and their babies
      should therefore receive the same perinatal care as booked patients.

PMID- 9542487
TI  - Fetal vibro-acoustic stimulation with a can--a clinical study.
AB  - OBJECTIVE: To assess the usefulness of the can as a fetal vibro-acoustic
      stimulator in the clinical environment. PATIENTS AND SETTING: 112 high-risk
      obstetric patients at Coronation Hospital, Johannesburg. METHOD: 161 vibro
      acoustic stimulation tests with a can and 159 non-stress tests (NSTs) were
      performed. The results of the can test were compared with those of the NSTs and
      with fetal outcome at delivery. RESULTS: The can test showed poor sensitivity
      (5/9). Three of the 4 false-negative results were due to placental abruption that
      occurred subsequent to the can test. The ability of the can test to predict a
      reactive NST and good fetal outcome was 94% (negative predictive value).
      CONCLUSIONS: In view of the reasonable negative predictive value, the test should
      be evaluated further as a screening test at primary care level, where there are
      few or no cardiotocographic facilities.

PMID- 9542488
TI  - The fascination and challenges of epidemiological research.

PMID- 9542489
TI  - HLA-A, -B, -DR and -DQ antigens in black patients with infective endocarditis.
AB  - In order to determine if genetically determined immune response factors could
      play a role in the pathogenesis of infective endocarditis in black patients, we
      performed HLA-A and HLA-B typing in 38 patients with this disease and HLA-DR and
      HLA-DQ typing in 33 and 27 of these individuals, respectively. HLA typing was
      also carried out in a control group of normal black adults. The HLA typing was
      done by means of a standard microlymphocytotoxicity test. No difference in HLA-A,
      HLA-B, HLA-DR and HLA-DQ antigen frequencies between patients and controls were
      noted. This study did not provide any evidence that genetic factors could
      contribute to a disposition to infective endocarditis.

PMID- 9542490
TI  - Two roles for caveolae in the cardiac myocyte?
AB  - The presence of caveolae in many cell types including heart myocytes is well
      established. It is hypothesized that caveolae may play a role in the storing of
      excess Ca2+ and may be instrumental in Ca2+ transients during contraction and
      relaxation in pathological conditions. Furthermore, the presence of substances in
      caveolae and in their membranes may imply a role in the importing and exporting
      of key molecules under physiological and pathological conditions. Secretory
      activity is also suggested by an electron micrograph of rat heart muscle.

PMID- 9542491
TI  - Respiratory muscle endurance in heart failure--the effect of clinical severity.
AB  - In chronic heart failure there is no single explanation for reduced effort
      tolerance. Recently, abnormalities of skeletal muscles, which include respiratory
      muscles, have been described in cases of chronic heart failure. The aim of this
      study was to investigate the effect of clinical severity of heart failure,
      measured by means of the Boston score, on respiratory muscle performance
      (strength and endurance). METHODS: Using the Boston score, we compared 20
      patients with chronic heart failure and low ejection fraction to 20 normal
      people, measuring maximal inspiratory mouth pressures (MIPs), maximal expiratory
      mouth pressures (MEPs) and endurance. Endurance was measured by repeated maximal
      static contractions of MIP and MEP as well as maximal voluntary ventilation
      (MVV). RESULTS: Inspiratory strength (MIP 75 +/- 34 cmH2O) but not expiratory
      strength (MEP 116.9 +/- 43.7 cmH2O) were reduced in heart failure patients,
      compared with controls (MIP 96.2 +/- 29.2, MEP 120.4 +/- 31 cmH2O). Endurance of
      inspiratory muscles was significantly reduced (P < 0.007) but not of expiratory
      muscles (P > 0.25). Clinical severity did not correlate with reduced endurance.
      CONCLUSION: Endurance of the inspiratory muscles was reduced in chronic heart
      failure unrelated to clinical severity.

PMID- 9542493
TI  - Effects of adrenaline, administered early or later after ischaemia, and
      reperfusion on the isolated rat heart.
AB  - OBJECTIVE: To evaluate the effect of adrenaline on cardiac function when given
      early or later in the reperfusion period. DESIGN: Prospective study. SETTING:
      University laboratory. PARTICIPANTS: Wistar rats. INTERVENTIONS: Isolated rat
      hearts were subjected to 45 minutes of normothermic ischaemic arrest. During
      reperfusion, adrenaline was administered early (2 minutes) or later (12 minutes)
      after termination of ischaemic arrest in addition to a short (5 minutes) or
      longer (10 minutes) recovery period before function was resumed. MEASUREMENTS AND
      RESULTS: Aortic and coronary flow, peak systolic pressure and heart rate were
      determined before arrest, 10 and 15 minutes after termination of ischaemic
      arrest. Adenosine triphosphate and creatine phosphate levels were also determined
      after cardioplegic arrest and reperfusion. Results indicate that early
      administration of adrenaline was not detrimental but that a longer recovery
      period after arrest resulted in significantly better cardiac function.
      CONCLUSION: After ischaemic arrest of the isolated rat heart a longer recovery
      period resulted in better cardiac function than a shorter period of recovery.

PMID- 9542492
TI  - Evaluation of ibopamine plus prazosin in congestive heart failure.
AB  - STUDY OBJECTIVE: To determine the acute haemodynamic response of a single dose co
      administration of ibopamine plus prazosin in patients with congestive heart
      failure. DESIGN: A double-blind, placebo-controlled randomised crossover study
      followed by a 2-week, open safety evaluation. SETTING: Wentworth Hospital,
      Durban. PATIENTS: 12 patients with congestive heart failure who were in
      functional class (NYHA) II-III. INTERVENTIONS: All patients underwent right heart
      catheterisation. On days 1 and 2 they received study drug or placebo plus
      prazosin and underwent haemodynamic recordings for 4 hours. RESULTS: Single-dose
      (200 mg) ibopamine plus prazosin augmented cardiac output (and index) and an
      early (0-60 minute) phasic response in the pulmonary capillary wedge pressure
      (PCWP) that did not appear to be influenced by the presence of prazosin. The
      increase in cardiac output was accompanied by a moderate decline in systemic
      vascular resistance (P = NS) without a change in heart rate. In the open
      evaluation, 8/14 patients reported adverse events. Six events were considered to
      be related to study medication of which one (dizziness) occurred in the
      haemodynamic phase. CONCLUSION: This study shows that ibopamine has beneficial
      haemodynamic effects in patients with moderate to severe heart failure. The
      increase in cardiac output was mild and sustained but with little change in
      systemic vascular resistance. The early rise in PCWP is not mediated by the alpha
      agonistic vasoconstrictor effects of ibopamine.

PMID- 9542494
TI  - Numerical simulation of pulsating flow in the aortic arch.
AB  - In order to investigate the flow profiles in the aorta a numerical three
      dimensional model of the aortic arch was created. The velocity fields were
      simulated by applying an inlet velocity corresponding to the physiological
      velocity of the pressure wave at the aortic valve. The velocity field
      distribution was found to be uniform throughout the model during the time of
      increasing inlet velocities. With decreasing inlet velocities a region of low
      flow developed in the descending portion of the model leading to recirculating
      flow at the inner wall. At this region of low flow the variation in velocity with
      time at the inner wall was approximately twice the variation at the outer wall.
      As a result of the recirculating flow, the wall shear stresses at the inner wall
      are low and oscillating, predisposing to the development of atherosclerosis. This
      model shows that transient fluid flow in the aortic arch can be simulated.
      Biological studies are needed to prove that this model can be used to predict
      sites of pathology.

PMID- 9542495
TI  - Cardiology in China and Mongolia.

PMID- 9542504
TI  - Editorial report.

PMID- 9542500
TI  - Lipids, the cardiovascular system and HRT.

PMID- 9542505
TI  - The European Journal of Surgical Oncology and the Internet II--World Wide Web
      standard networks and clinical applications.

PMID- 9542506
TI  - Laparoscopic resection of colorectal cancer--high art or access artistry?

PMID- 9542507
TI  - Self-perceptions of women after early breast cancer surgery.
AB  - AIMS: To discover satisfaction with treatment decision and the late influences of
      surgery for early breast cancer on the lives and self-perceptions of women.
      METHODS: A two-part mail survey was returned by 90 women aged 2.8-7.6 years after
      breast-conserving treatment (BCT) and by 56 women aged 3.0-8.0 years after
      modified radical mastectomy (MRM). RESULTS: Approximately one-third of all
      patients felt the information and time before the treatment decision was
      inadequate. Most women in both treatment groups had participated in treatment
      decision-making. When the surgeon alone had made the choice it did not affect
      satisfaction with the treatment result. Few patients regretted the treatment
      modality chosen. The majority of patients felt no discomfort in their treated
      breast, but a quarter of all the women suffered from rib pain. Fifteen of 52
      sexually active women reported of reduced breast pleasure sensation in their
      resected breast. The women in both treatment groups were asked to score a summary
      satisfaction index (SSI) on a scale of 0-10 for seven different areas of life:
      cosmesis, function, work, home, recreation/sports, social life and sexuality. SSI
      was used as a measure of quality of life. There was a difference in all these
      categories between BCT and MRM groups, the former giving significantly higher
      values. Post-menopausal women tended to be more-satisfied than younger women and
      women over 70 years showed no difference in satisfaction between the two
      treatment modalities. Treatment of early breast cancer caused little morbidity in
      the long run. After MRM slightly more local symptoms were reported. CONCLUSIONS:
      Most women treated with breast-conserving surgery esteemed their life normal or
      close to normal, giving us a reason to favour BCT when suitable. For women over
      70 years old mastectomy remains a viable alternative.

PMID- 9542508
TI  - Prediction of nipple and areola involvement in breast cancer.
AB  - AIMS: To find a pre-operative test for nipple and areola involvement in breast
      cancer. METHODS: Areola-tumour distance was measured in 140 consecutive patients
      (median age 45, range: 23-83) undergoing a mastectomy. We analysed whether nipple
      and areola correlated with areola-tumour distance, tumour size, nodal status,
      perinodal involvement and lymphatic embolization. RESULTS: The nipple was
      involved in 22 (16%) cases and this correlated with tumour size, number of lymph
      nodes, perinodal extension and presence of lymphatic emboli. In all these 22
      cases, the tumour was within 2.5 cm of the areola. Tumour size, however, could
      not predict nipple involvement in tumours within 2.5 cm of the areolar edge.
      CONCLUSIONS: In the one-fifth of cases where the tumour is over 2.5 cm from the
      areola, preserving the nipple and areola for reconstruction may be worthwhile. In
      remaining cases, some other predictive test for nipple involvement would be
      necessary.

PMID- 9542509
TI  - Axillary lymphadenectomy prepared by fat and lymph node suction in breast cancer.
AB  - AIMS: To describe a new technique of axillary dissection and evaluate the
      results. METHODS: Axillary lymphadenectomy prepared by fat and lymph node suction
      was performed on 43 patients with breast cancer and uninvolved axilla on physical
      examination. The mean follow-up was 18 months (range 12-27). After lipolysis and
      liposuction of the axilla, lymph node dissection was performed by axilloscopy in
      patients treated with conservative surgery. For patients undergoing modified
      radical mastectomy, a mastectomy with open axillary dissection was carried out.
      The axillary space was drained until less than 20 ml of lymphorrhea was being
      produced per day. Seventeen modified radical mastectomies (group M) and 26
      lumpectomies (group L) were performed. RESULTS: No injury of muscles, vessels or
      nerves was observed. An average of 13.6 lymph nodes (8-31) were removed. In group
      L, the mean number of lymph nodes removed by liposuction, axilloscopy and control
      incision was 2.5, 5.4 and 4.2, respectively. In group M, the mean number of lymph
      nodes removed was 14. None of the 589 lymph nodes examined showed any
      pathological trauma. Fourteen patients (32%) had more than one histologically
      positive node. The mean quantity of lymphorrhea was 390 ml in group M and 275 ml
      in group L. The mean duration of drainage was 6 days in group M and 5 days in
      group L. Four patients had seromas which required punctures. Two patients had
      shoulder restriction (movements < 90 degrees) at 12 months. No arm oedema was
      seen. CONCLUSIONS: Axillary lymphadenectomy prepared by fat and lymph node
      suction is a reliable and effective procedure. However, it does not appear to be
      better than standard dissection as regards post-operative complications, except
      for arm oedema, but this must be confirmed by further studies.

PMID- 9542510
TI  - Modern trends in breast cancer therapy: towards less lymphoedema?
AB  - AIMS: To review from the evidence, with special reference to axillary node
      management, whether the incidence of lymphoedema following breast cancer
      treatment is falling in modern breast practice. CONCLUSIONS: The incidence of
      lymphoedema does seem to be reducing with modern approaches to breast cancer
      management. Axillary treatment seems to determine its development but more
      studies looking specifically at this problem are needed.

PMID- 9542511
TI  - The lack of age as a significant prognostic factor in non-metastatic breast
      cancer.
AB  - AIMS: To determine the prognostic significance of age at diagnosis in women with
      non-metastatic breast cancer. METHODS: A retrospective review of all newly
      diagnosed breast cancer in women between 1975 and 1991 was carried out at a
      tertiary Oncology Referral Centre. Patients were divided into three age groups: <
      40 years, 40-50 years and > 50 years. Demographic and management/outcome details
      were collected from patients with UICC stages I-III. The effect of age on overall
      and relapse free survival was analysed by standard statistical methods. RESULTS:
      Of 1289 new cases registered during the study period, 710 (55%) were UICC stages
      I-III. Of the latter group 250 (35%) women were in the age group of less than 40
      years, 237 (33%) were between 40 and 50 years and 223 (32%) were older than 50
      years. Women from the younger age group had a higher proportion of breast
      conserving surgery, and adjuvant chemo- and radiation therapy, while the
      proportion of hormone therapy usage was higher in older women. There was no
      difference in overall survival (P = 0.64) and relapse-free survival (P = 0.53)
      between the three age groups. CONCLUSION: In this study, age was not a prognostic
      factor in predicting overall or relapse-free survival in women with breast
      cancer.

PMID- 9542512
TI  - Assessment of c-erbB2 and vascular endothelial growth factor mRNA expression in
      fine-needle aspirates from early breast carcinomas: pre-operative determination
      of malignant potential.
AB  - AIMS: Although axillary lymph nodes status, tumour size, hormonal-receptor status
      and histological grade at diagnosis are frequently used to orient the treatment
      of breast cancer patients, some tumours recur in patients with early stage
      disease. Pre-operative assessment of individual tumour characteristics, based on
      oncogenes and growth factors related to tumour growth, invasion or metastasis,
      may guide the treatment for patients with breast carcinomas. METHODS: We examine
      here the prognostic significance of cyclin D1, urokinase type plasminogen
      activator, vascular endothelial growth factor (VEGF), platelet-derived growth
      factor, and c-erbB2 expression in pre-operatively obtained fine-needle aspirates
      from breast carcinomas less than or equal to 3 cm in size. Correlation between
      mRNA expression of these factors and clinicopathological characteristics was
      analysed. RESULTS: The level of c-erbB2 mRNA expression was significantly higher
      in tumours with lymph node metastases than in those without lymph node
      metastases. VEGF mRNA expression positively correlated with the degree of
      angiogenesis as quantitated by immunohistological staining with a CD31 monoclonal
      antibody. CONCLUSIONS: Analysis of c-erbB2 and VEGF mRNA expression in fine
      needle aspirates may be useful in assessing the malignant potential of individual
      breast carcinomas, leading to a pre-operative discrimination of a high-risk
      group.

PMID- 9542513
TI  - Loss of heterozygosity at microsatellite marker sites for tumour suppressor genes
      in oesophageal adenocarcinoma.
AB  - AIMS: Loss of cell cycle control is an important step in the development of human
      tumours. A number of tumour suppressor genes are involved in cell cycle control,
      including p16, p53 and Rb. The aim of this study was to seek evidence of
      deletions of these genes in oesophageal adenocarcinoma. METHODS: Paired (tumour
      and normal squamous epithelium) frozen tissue samples from 12 patients were
      analysed by polymerase chain reaction (PCR) for loss of heterozygosity (LoH) at
      five microsatellite marker sites (two each for p16 and Rb, one for p53).
      Aneuploid tumour cell populations were sorted by flow cytometry prior to PCR, to
      eliminate stromal cell contamination. RESULTS: Of the 12 tumours, 11 (92%) had
      LoH at one or more loci. LoH at the p53 locus occurred in nine of 12 tumours, at
      one or both p16 loci in seven of 11 tumours, and at one or both Rb loci in eight
      of 12 tumours. Five tumours had LoH at two tumour suppressor gene loci, and a
      further four tumours had LoH at loci for all three genes. CONCLUSIONS: Allelic
      deletions of p53, p16 and Rb are common in oesophageal adenocarcinoma, and may be
      important in the development of this disease.

PMID- 9542514
TI  - Transforming growth factor alpha immunoreactivity in human gallbladder and
      extrahepatic biliary tract tumours.
AB  - AIMS: Transforming growth factor alpha (TGF-alpha), a protein structurally
      similar to epidermal growth factor (EGF), is implicated in the development of
      many human tumours. This study examines the expression of TGF-alpha in
      gallbladder and extrahepatic biliary tract tumours in which EGFR expression has
      been previously shown to be important. METHODS: A monoclonal antibody to the TGF
      alpha protein was used to investigate the immunohistochemical expression of TGF
      alpha in carcinoma of the gallbladder (n = 13), common bile duct (CBD) (n = 6)
      and ampulla of Vater (n = 8). Tissues from cases of chronic cholecystitis (n =
      11), gallbladder dysplasia (n = 3) and adenoma (n = 1), and ampullary carcinoma
      in situ (CIS) (n = 3) were used as non-malignant controls. These cases were
      previously studied for EGFR expression. RESULTS: TGF-alpha overexpression,
      defined as intense immunoreactivity in more than two-thirds of cells
      immunostained for TGF-alpha, was present in most gallbladder carcinomas (n = 10;
      77%) but with no significant differences in expression between different tumour
      grades. None of the cases of gallbladder dysplasia or chronic cholecystitis had
      strong TGF-alpha expression and this was significantly different from the
      carcinomas (P = 0.013 and P = 0.0001, respectively; chi 2 test), although a few
      cases of chronic cholecystitis showed weak (n = 4), moderate (n = 6) or no (n =
      1) immunoreactivity. A few ampullary carcinomas (n = 2; 25%) and CIS (n = 1;
      33%), and half of the CBD carcinomas (50%) had strong TGF-alpha immunoreactivity.
      There was correlation between TGF-alpha and EGFR immunoreactivity in the tumour
      cases (r = 0.70, r2 = 0.49, P = 0.0001; simple regression analysis), although the
      rate of EGFR immunoreactivity in CBD and ampullary carcinomas was somewhat higher
      than that of TGF-alpha. However, no statistically significant correlation between
      TGF-alpha expression with patient survival or tumour recurrence (r = 0.11, r2 =
      0.012, P = 0.65; simple regression analysis) was found. CONCLUSIONS: Increased
      TGF-alpha expression occurs more frequently in gallbladder carcinoma than in
      gallbladder dysplasia, chronic cholecystitis, CBD or ampullary tumour, with no
      specific relationship to tumour grade, suggesting that TGF-alpha overexpression
      occurs early in the development of gallbladder cancers, and that biliary tract
      cancers have a different molecular origin. Correlation was found between TGF
      alpha and EFGR expression in gallbladder and biliary tract tumours.

PMID- 9542515
TI  - Erythrocyte membrane stearic to oleic acid ratio in carcinoma of the gallbladder:
      a preliminary study.
AB  - AIMS: The role of erythrocyte membrane stearic to oleic acid ratio (saturation
      index) as a marker of malignancy is still unclear, though an association has been
      found in colorectal carcinoma, bronchogenic carcinoma, leukaemia, lymphoma and in
      hepatic malignancies. This study aims to investigate the role of the saturation
      index in primary carcinoma of the gallbladder. METHODS: This paper describes the
      results of the stearic to oleic acid ratio determination in 26 subjects with
      either cholelithiasis or carcinoma of the gallbladder, also including a group of
      age- and sex-matched controls, using gas chromatography. This is the first report
      of the saturation index in carcinoma of the gallbladder. RESULTS: A significantly
      lower saturation index was observed in patients with carcinoma of the gallbladder
      than with cholelithiasis (t = 2.19, P = 0.043, T = 47, P < 0.05, Wilcoxon P <
      0.001, F = 2192.23, P < 0.001; 95% CI 18.45-30.44) and controls (t = 2.5, P =
      0.024, T = 36, P < 0.05, F = 10904.11, P < 0.001, Wilcoxon P < 0.001; 95% CI
      52.42-63.39). Among the carcinoma patients a further lowering was noted in stage
      IV disease compared with stage III (T = 6, P < 0.05). CONCLUSIONS: These changes
      are probably due to a marked increase in oleic acid content at the expense of
      stearic acid. This lowering of the saturation index in carcinoma of the
      gallbladder is similar to that observed previously in the other malignancies.

PMID- 9542516
TI  - Screening for colorectal cancer reduces emergency admissions.
AB  - AIMS: Colorectal cancer is common and accounts for over 15,000 deaths annually in
      England and Wales. Up to 30% of these patients require emergency surgery.
      Screening for colorectal cancer can reduce the mortality of colorectal cancer.
      This study addresses the impact of a population-based screening study on
      emergency admissions with colorectal cancer. METHOD: From 1981 a randomized trial
      of Faecal Occult Blood (FOB) screening has been undertaken in the Nottingham
      area, recruiting over 150,000 patients. The present study examined the records of
      patients enrolled in this study who presented as an emergency with colorectal
      cancer. RESULTS: Colorectal cancer was identified in 1962 cases, of which 468
      (23.9%) presented as emergencies. The overall compliance was 60% (proportion of
      individuals completing at least one test). There were significantly fewer
      emergencies in the Screen-detected group compared with the Control group (P = <
      0.0001). This group also had a significantly reduced 30-day mortality and a lower
      stoma rate than the Control group. Conversely the Non-responders had a
      significantly greater proportion of emergency admissions and a significantly
      increased stoma rate compared with the Control group. CONCLUSIONS: Screening for
      colorectal cancer using a faecal occult blood test can significantly reduce the
      number of emergency presentations with colorectal cancer. It is likely that the
      introduction of a national programme of screening for colorectal cancer would
      lead to increased compliance and that this would lead to a significant reduction
      in the emergency workload on the National Health Service from colorectal cancer.

PMID- 9542517
TI  - Computed tomography for the detection of neck node metastases in melanoma
      patients.
AB  - AIMS: To assess the value of CT scanning for detection of lymph node metastases
      in the neck. METHODS: The appearance and site of the metastases was studied, as
      well as the sensitivity and specificity of CT. RESULTS: Nodal metastases did not
      always show a high contrast uptake and nodal density therefore cannot be used as
      a criterion for metastasis. Irregular contrast enhancement was seen in seven of
      the 21 tumour-positive necks. Frequently, metastases in the parotids, superficial
      nodes in the neck and in the posterior triangle were seen. The sensitivity and
      specificity of palpation and CT scanning were 87 and 100%, respectively.
      CONCLUSIONS: However, because small, clinically occult, melanoma metastases were
      frequently overlooked on CT, the role of this imaging modality in assessing
      occult metastases remains limited. Based on recent data from literature it is
      reasonable to speculate that ultrasound guided fine needle aspiration cytology
      (FNAC) will prove to be more effective than a non-invasive staging procedure of
      the neck in melanoma patients.

PMID- 9542518
TI  - Breast cancer--mysteries of the axillary pyramid.

PMID- 9542519
TI  - Endothelin-1 and tumour development.
AB  - There has been a growing conviction amongst oncologists that cancer is a disease
      characterized by changes in specific molecules. These changes include alteration
      in the structure, regulation or quantity of growth factors and their receptors,
      signal transducers and the proteins encoded by dominant or suppressor/recessive
      oncogenes. The role of endothelin (vasoactive peptide) in tumour cell signal
      transduction and mitogenesis and induction of endothelial cell growth and
      angiogenesis in tumour growth is discussed in this article.

PMID- 9542521
TI  - The (continued) importance of the hypothesis in surgical oncology research.

PMID- 9542520
TI  - Appraisal of transplantation for malignant tumours of the liver with special
      reference to early stage hepatocellular carcinoma.
AB  - The enthusiasm to treat or even cure patients with unresectable hepatobiliary
      malignancy by total hepatectomy and liver transplantation has considerably
      diminished. Nowadays, due to organ-donor shortage, patients have to be selected
      with predictable likelihood for long-term survival. According to own experience
      and a review of the literature, liver transplantation may be considered in
      unresectable early stage hepatocellular and proximal bile duct carcinoma, the
      uncommon entities fibrolamellar carcinoma, epithelioid haemangioendothelioma and
      hepatoblastoma as well as in liver metastases from neuroendocrine tumours. At
      present, advanced stages of hepatocellular and proximal bile duct carcinoma, as
      well as intrahepatic bile duct carcinoma, haemangiosarcoma and metastases from
      nonendocrine tumours, should be excluded from transplantation. In order to cure
      the cancer-bearing disease, liver transplantation might be the ideal treatment
      for small but still resectable hepatocellular carcinoma with underlying
      cirrhosis. Our retrospective comparison of survival after resection and
      transplantation for early stage hepatocellular carcinoma does not reveal a
      significant difference. Although a tendency has been observed in favour of
      transplantation, resection of these tumours is still justifiable, not least
      because of donor organ shortage.

PMID- 9542522
TI  - Huge non-functioning pancreatic cystic neuroendocrine tumour: a case report.
AB  - A case of an 18-cm large cystic, non-functioning endocrine (islet cell) tumour
      located at the tail of the pancreas in a 29-year-old Caucasian female is reported
      here. Pre-operative radioimmunoassays for pancreatic peptides were negative,
      while immunohistochemistry confirmed the neuroendocrine nature of the tumour.
      This is the largest cystic non-functioning islet-cell tumour so far described.

PMID- 9542523
TI  - Primary angiosarcoma of the breast.
AB  - We report a case of a 44-year-old woman with primary angiosarcoma of the left
      breast. An excisional biopsy was performed initially and the mass was interpreted
      as angiosarcoma. The pre-operative staging provided no evidence of metastasis.
      The patient then underwent a left mastectomy with the placement of an expandable
      prosthesis. For 3 months the prosthesis was progressively expanded to the desired
      size and it was then replaced with a permanent one. Primary angiosarcoma of the
      breast is a rare and often misdiagnosed disease. Treatment options are numerous
      and conflicting. The diagnostic approach and treatment options from the
      literature are presented and discussed.

PMID- 9542524
TI  - Mucoepidermoid carcinoma of the breast: a case report and review of the
      literature.
AB  - Muco-epidermoid carcinoma is a rare primary of the breast with previous reports
      of only 15 cases. As the following case report demonstrates, it can be very
      difficult to diagnose on aspiration cytology and a negative result should be
      interpreted with caution.

PMID- 9542525
TI  - Nodular fasciitis-type papillary thyroid carcinoma. Presentation of a new case.

PMID- 9542526
TI  - Rare microsatellite polymorphisms in the DNA repair genes XRCC1, XRCC3 and XRCC5
      associated with cancer in patients of varying radiosensitivity.
AB  - DNA repair defects might contribute both to cancer progression and to the extreme
      reactions to radiotherapy observed in approximately 5% of patients. Polymorphic
      microsatellites in three DNA repair genes, XRCC1, XRCC3 and XRCC5, were analyzed
      for possible linkage to cancer status or clinical radiosensitivity. XRCC1, 3 and
      5 proteins are involved in single-strand DNA break rejoining, recombinational
      repair, and double-strand DNA break rejoining respectively. Mendelianly inherited
      microsatellite polymorphisms in these genes were analyzed in three groups:
      volunteers with no cancer history; radiosensitive cancer patients; cancer
      patients with acceptable reactions to radiotherapy. Rare heterozygous alterations
      in all three gene regions were found solely in the cancer subpopulation.
      Association testing between these rare polymorphisms and cancer status revealed a
      significant association for XRCC1 (P = 0.005), and XRCC3 (P = 0.004). There was
      also an association between these polymorphisms and clinical radiosensitivity for
      XRCC1 (P = 0.03), and XRCC3 (P = 0.005).

PMID- 9542527
TI  - Death of solid tumor cells induced by Fas ligand expressing primary myoblasts.
AB  - Anticancer therapy for solid tumors suffers from inadequate methods for the
      localized administration of cytotoxic agents. Fas ligand (FasL) has been reported
      to be cytotoxic to a variety of cells, including certain tumor cell lines. We
      therefore postulated that myoblasts could serve as non-transformed gene therapy
      vehicles for the continuous localized delivery of cytotoxic anticancer agents
      such as FasL. However, contrary to previous reports, fluorescence activated cell
      sorting (FACS) analyses revealed that both primary mouse and human myoblasts
      express Fas, the receptor for FasL. To avoid self-destruction and test the
      cytotoxic potential of myoblasts, the cells were isolated from mice deficient in
      Fas (lpr/lpr), the mouse counterpart of human autoimmune lymphoproliferative
      syndrome (ALPS). These primary mouse myoblasts were transduced with a retroviral
      vector encoding mouse FasL and expression of a biologically active and soluble
      form of the molecule was confirmed by the apoptotic demise of cocultured Fas
      expressing Jurkat cells, the standard in the field. To test whether the lpr
      myoblasts expressing FasL could be used in anticancer therapy, human
      rhabdomyosarcoma derived cell lines were assayed for Fas and then tested in the
      apoptosis coculture assay. The majority of Fas-expressing muscle tumor cells were
      rapidly killed. Moreover, FasL expressing myoblasts were remarkably potent;
      indeed well characterized cytotoxic antibodies to Fas were only 20% as efficient
      at killing rhabdomyosarcoma cells as FasL expressing myoblasts. These findings
      together with previous findings suggest that primary myoblasts, defective in Fas
      but genetically engineered to express FasL, could function as potent anticancer
      agents for use in the localized destruction of solid tumors in vivo by three
      synergistic mechanisms: (1) directly via Fas/FasL mediated apoptosis, (2)
      indirectly via neutrophil infiltration and immunodestruction, and (3) as
      allogeneic inducers of a bystander effect via B and T cells.

PMID- 9542528
TI  - Maintenance of hypomethylation status and preferential expression of exogenous
      human MDR1/PGY1 gene in mouse L cells by YAC mediated transfer.
AB  - Selection of cells for resistance to vincristine or doxorubicin often induces
      overexpression of the multidrug resistance (MDR) genes, which encode the cell
      surface P-glycoproteins, as a result of gene amplification, transcriptional
      activation, or mRNA stabilization. The LMD1 and LMD4 cell lines were established
      after the transfer into mouse L cells of two independent yeast artificial
      chromosome clones containing 300 and 850 kb, respectively, of the human MDR
      locus. The human MDR1/PGY1 gene, but not the endogenous mouse mdr1a and mdr1b
      genes, was overexpressed as a result of gene amplification and transcriptional
      activation in various sublines of LMD1 and LMD4 cells selected for resistance to
      vincristine. Then we asked why human MDR1/PGY1 gene, but not mouse relevant gene,
      was expressed. Determination of the methylation status of cytosine residues at
      Msp I/Hap II cleavage sites (CCGG) in the promoter regions of human MDR1/PGY1 and
      mouse mdr1a revealed hypomethylation and hypermethylation of the human and mouse
      genes, respectively in LMD1, LMD4, and their vincristine-resistant derivatives.
      Various vincristine-resistant sublines were also established after exposure of
      LMD1 cells for 48 h to 5-aza-2'-deoxycytidine, an inhibitor of DNA
      methyltransferase. These sublines exhibited overexpression of mouse mdr1a and
      mdr1b, but not of human MDR1/PGY1, as well as hypomethylation of the mouse mdr1a
      promoter region. Thus, the selective expression of human or mouse MDR genes in
      this cell system appears to be related to the methylation status of the
      respective gene promoter regions.

PMID- 9542529
TI  - Organization and expression of human telomere repeat binding factor genes.
AB  - The ends of mammalian chromosomes terminate in structures called telomeres.
      Recently a human telomere repeat binding factor (TRF1) that binds the vertebrate
      TTAGGG telomeric repeat in situ was isolated by Chong et al. (1). TRF1 regulates
      telomere length (2), which is often altered in cancer cells. To understand their
      genetic organization, TRF1 genes were localized to human chromosomes 13cen,
      21cen, and Xq13 by analysis of human monochromosomal hybrids, and by fluorescent
      in situ hybridization. We also confirmed the recent localization of a human TRF1
      gene to chromosome 8, and provide evidence that this locus is alternatively
      spliced. In contrast to the TRF1 genes on chromosomes 8 and X, the chromosomes 13
      and 21 TRF1 genes contained a 60 bp deletion in the coding region. The results
      suggest that two distinct forms of TRF1 are expressed and that the TRF1 gene
      family includes at least three pseudogenes whose dispersal in the human genome
      may have occurred via cDNA intermediates.

PMID- 9542530
TI  - Depletion of mitochondrial DNA by ddC in untransformed human cell lines.
AB  - In order to study the interaction between the nuclear and mitochondrial genomes
      we have developed a non-transformed cell system. It is based upon the complete
      removal of mtDNA from fibroblasts by treatment with a nucleoside analogue, 2',3'
      dideoxycytidine (ddC). After exposure to ddC we were able to generate viable
      fibroblasts devoid of mtDNA and to successfully repopulate them with exogenous
      mitochondria. This model system will be useful in characterizing nuclear
      mitochondrial interactions and in studying the effects of different nuclear
      backgrounds on the expression of different primary defects of mtDNA associated
      with human disease.

PMID- 9542531
TI  - Colocalization of P2Y2 and P2Y6 receptor genes at human chromosome 11q13.3-14.1.
AB  - Extracellular nucleotides mediate a number of physiological responses through
      either ligand gated P2X or G protein-coupled P2Y receptors. To date, six P2Y
      receptor subtypes, P2Y1-P2Y6, have been cloned. We mapped the human P2Y6 receptor
      gene to chromosome 11q13.3-13.5. Oligonucleotide primers complementary to a part
      of the human P2Y6 receptor cDNA were used to amplify a region from genomic DNA
      from a panel of mouse/human somatic cell hybrid cell lines, each containing a
      single human chromosome. A PCR product of the expected size (714 bp) resulted
      from a single hybrid cell line containing human chromosome 11. The gene was
      further localized to a region of chromosome 11 using a subchromosomal hybrid
      panel containing different segments of chromosome 11. Based on the specific PCR
      product obtained and its Southern hybridization to the P2Y6 receptor cDNA, the
      human P2Y6 receptor gene was localized to chromosome 11q13.3-13.5. Previously, we
      have localized the P2Y2 receptor gene to human chromosome 11q13.5-14.1. This is
      the first report of the clustering of the P2 receptor genes. The clustering of
      these two P2Y receptor subtypes suggests a relatively recent expansion of the
      gene family by gene duplication.

PMID- 9542532
TI  - Mapping of the human P84 gene to the subtelomeric region of chromosome 20p.
AB  - P84 is a novel neural adhesion molecule that may play an important role in
      synaptogenesis. We have recently cloned a murine cDNA encoding the P84 adhesion
      molecule. The human homologue of P84 has previously been isolated (by others) as
      a brain specific cDNA containing CCA repeats. We have mapped the human P84 gene
      to the subtelomeric region of chromosome 20p (20p13) by FISH. In addition, we
      have been able to place P84 onto the high resolution physical map of the human
      genome by utilizing the Unigene database. P84 maps to several YAC clones, between
      STS markers IB255 and WI-9632, and very close to the polymorphic marker D20S199,
      in an interval of less than 1 Mb on 20p13. P84 is a strong candidate gene for
      neurological disorders which map into this region.

PMID- 9542533
TI  - [XXVIII Argentine Congress on Gastroenterology, XV Argentine Congress on
      Digestive Endoscopy, V meeting of Pediatric Gastroenterology and Nutrition.
      Rosario, 21-24 September 1997. Abstracts].

PMID- 9542535
TI  - Canadian Digestive Diseases Week. 37th Annual meeting of the Canadian Association
      of Gastroenterology in conjunction with the Canadian Association for the Study of
      the Liver. Banff, Alberta, Canada. March 1-8, 1998. Abstracts.

PMID- 9542536
TI  - Cytokine and chemokine signaling in leukocyte development and function. 32nd
      National meeting of the Society for Leukocyte Biology. Baltimore, Maryland, USA.
      December 4-7, 1997. Abstracts.

PMID- 9542537
TI  - Membership directory, Society for Leukocyte Biology.

PMID- 9542538
TI  - XII Meeting of Brazilian Society of Protozoology and XXIII Annual meeting on
      Basic Research in Chagas' Disease. Caxambu, MG, Brasil, 5-8 November 1996.
      Abstracts.

PMID- 9542539
TI  - Reconsidering the effects of seat belt laws and their enforcement status.
AB  - The debate over the benefits of mandatory seat belt laws and their enforcement
      status has focused on a controversial empirical enigma: why have these policies,
      which appear to have increased belt use sharply, had a relatively small impact on
      traffic fatalities? In this paper, I offer new insights into this question by
      examining panel data on observed belt use from the National Highway Traffic
      Safety Administration and self-reported data on belt use from pooled cross
      sections of the Centers for Disease Control and Prevention's 1985-1993 Behavioral
      Risk Factor Surveillance System. By exploiting the panel nature of these data, I
      demonstrate that prior estimates, which have not conditioned on the unobserved
      time-varying determinants of belt use, have dramatically overestimated the impact
      of seat belt laws and their enforcement status on belt use. The true effects are
      more consistent with the modest impact these policies have had on traffic
      fatalities without having to appeal to the possibility of risk compensation by
      drivers. However, I find strong evidence in support of the selective recruitment
      hypothesis. Belt use among those most likely to be involved in traffic accidents
      (e.g. males, drinkers of alcohol, the young) has been significantly less
      responsive to seat belt laws and their enforcement status.

PMID- 9542540
TI  - Analysis of circumstances and injuries in 217 pedestrian traffic fatalities.
AB  - We performed a retrospective analysis of 217 pedestrian traffic fatalities in
      Seattle, WA, U.S.A. that occurred over a six-year period using medical examiner
      records with essentially all of the deaths examined by autopsy. The annual
      pedestrian fatality rate for the county averaged 2.0/100,000 for all ages and
      both sexes, and the age-specific rate varied from 1.0/100,000 for the 22-34 year
      age group to 1.5/100,000 for children under seven years and 7.0/100,000 for ages
      70 years and older. Males had a 50% higher rate than females. Fatal accidents
      were most common during December and January and during the evening hours.
      Wednesday had the greatest number of accidents leading to death, 79% higher than
      the Saturday weekend rate. Of those tested, 24% had ethanol in their blood. 66%
      of the fatal injuries occurred on city or residential streets, and 29% occurred
      on major thoroughfares. A single urban highway accounted for 12% of pedestrian
      fatalities and represented a particularly hazardous traffic environment. Fatal
      head injuries and severe chest injuries were present in 73% of cases; injuries
      involving multiple sites were present in 60%. There were few significant
      differences in the extent of injuries with respect to vehicle speed or type of
      vehicle. Head injuries were much less common in the oldest age group, probably
      because elderly pedestrians were more vulnerable to death from less severe trunk
      and extremity injuries. Severe chest injury was the most important predictor of
      death occurring at the scene.

PMID- 9542541
TI  - Comparison of lifestyle and substance use factors related to accidental injuries
      at work, home and recreational events.
AB  - The purpose of this study was to examine whether risk factors vary for injuries
      that occur at work, at home, at recreational events and at multiple settings.
      Three major types of factors were investigated: lifestyle factors such as sleep,
      stress and exercise; substance use; and demographic characteristics. Data were
      obtained from a household survey of 882 Ontario adults. In order to determine
      whether different factors were related to different kinds of accidental injuries,
      chi 2 tests were conducted among five injury groups: no injuries; work; home;
      recreational; and multiple injury episodes (i.e. at least two separate injury
      episodes in two different settings). The first set of comparisons were conducted
      between those with zero injuries and each of the aforementioned four injury
      groups. Those with multiple injury episodes were significantly more likely than
      those with no injuries to be single, under the age of 30, and have lifestyle
      problems (i.e. sleep problems, financial problems and a desire for counselling)
      and substance use/problems (i.e. cigarettes, alcohol, licit and illicit drugs).
      For comparisons between each of the work, home and recreational injury groups and
      no injury group, eight factors were significant altogether, but no single factor
      was significantly related to more than one injury group. Contrasts between all
      combinations of injury group pairs (i.e. excluding the no injury group) indicated
      that risk factors for those with multiple injury episodes differed significantly
      from those with home and recreational injuries for several characteristics. This
      exploratory study provides some support that risk factors may vary, depending on
      the injury group.

PMID- 9542542
TI  - Ottawa-Carleton commuter cyclist on- and off-road incident rates.
AB  - This analysis overcomes the known limitations of police and emergency room
      bicycle accident databases through use of a survey that asked cyclists to
      indicate their accident history as well as their regular commute route to work or
      school. By relating the route information of the 1604 respondents (52.5% of the
      distributed questionnaires) to facility attributes in a Geographic Information
      System, defensible estimates of travel exposure on roads, off-road paths and
      sidewalks were developed. The relative rates of collisions on the three different
      facility types were not statistically different from 1.0. The relative rates for
      falls and injuries suggest it is safest to cycle on-road followed by off-road
      paths and trails, and finally least safe on sidewalks. While there were no major
      injuries reported on sidewalks, the relative rate for these events on paths was
      greater than the rate for roads. The absolute event rates per bicycle kilometre
      were found to be between 10 and 41 times higher than similar rates for automobile
      travel. Results suggest a need to discourage sidewalk cycling, and to further
      investigate the safety of off-road paths/trails. The analysis also demonstrates
      the need for bicycle travel exposure information and the use of more than just
      collision databases for bicycle safety analysis.

PMID- 9542543
TI  - The situational risks of young drivers: the influence of passengers, time of day
      and day of week on accident rates.
AB  - This paper provides new insight into the situational risks of young drivers,
      especially in terms of the passenger effect. Two 1988 data bases from the Ontario
      Ministry of Transportation were used to estimate accident involvement rates by
      number of passengers, time of day and day of the week--first individually and
      then for all two-way combinations with the passenger variable. Accident data were
      derived from police reports for all accidents involving a fatality, personal
      injury or property damage exceeding $700. Estimates of exposure were based on the
      most up-to-date provincial travel survey available at the time of the study.
      Results indicate that the accident involvement rates of 16-19 year old drivers
      are higher than those of 20-24 and 25-59 year olds in all situations that were
      examined, but that they were disproportionately high on weekends, at nighttime
      and with passengers. The results of the passenger variable are particularly
      interesting because, unlike weekends and nighttime, the negative effect of
      passengers on overall accident rates was evident only for 16-19 year old drivers.
      This effect was quite pronounced for both sexes, with accident involvement rates
      being approximately twice as high with passengers as without. For 16-19 year
      olds, accident rates were also significantly higher for two or more passengers
      versus one passenger. The highest rates for this age group occurred with
      passengers at nighttime. Possible explanations for these patterns and policy
      implications are discussed.

PMID- 9542544
TI  - Studies on tractor related injuries in northern India.
AB  - Epidemiological studies were conducted in two phases each of 1 year duration in
      nine and 30 villages, respectively, in two northern states of India.
      Investigations were carried out to determine the causal factors, the activities
      involved and severity of injuries for farming and non-farming activities in
      tractor related accidents. A total of 76 cases involving five fatalities and 71
      non-fatal injuries were recorded. The pattern of tractor related injuries in
      India have been found to be very different compared to those reported from highly
      industrialized countries. Fifty-four percent of tractor related injuries in the
      first phase and 49% in the second phase were because of non-farming activities.
      Of the total injuries recorded in both the phases only 1 and 6% were tractor
      related. A major cause of tractor related injuries were collisions. In the two
      phases 28 and 40% injured were passengers on tractor or trailer.

PMID- 9542545
TI  - A study of commercial vehicle safety alliance's out-of-service criteria.
AB  - This paper summarizes a two-phase project that reviewed the Commercial Vehicle
      Safety Alliance's out-of-service criteria for vehicles. The first phase examined
      relevant background information and conducted a questionnaire survey of CVSA
      inspectors and industry representatives. The second phase of the project involved
      extensive collection and evaluation of accident data. The results of both phases
      show a high level of support, in terms of contribution to vehicle accidents, for
      four of the vehicle criteria (regarding brakes, load securement, tires, and
      wheels and rims). There was some support for coupling devices, fuel systems,
      lighting devices, steering and suspension. The support for the remaining vehicle
      criteria (exhaust systems, frames, van and open top trailer bodies, and
      windshield wipers) was little to none. Further research continuing the study of
      accident data is recommended to confirm these findings. However, the data must be
      collected in a consistent and detailed manner if accurate information on the
      relationship of accidents and vehicle criteria is to be established.

PMID- 9542546
TI  - Impact from changes in Illinois drivers license renewal requirements for older
      drivers.
AB  - In late 1989, Illinois revised the length of license term and renewal
      requirements for older drivers. The term was shortened from 4 to 2 years for
      those ages 81-86 and 1 year for those ages 87 and up. A mandatory road test which
      had been required at renewal for all drivers ages 69 and over, was eliminated for
      those ages 69 to 74. Data are available to explore the impact of these changes on
      crashes, fatal crashes, crash rates, and licensure rates of senior drivers.
      Comparisons are made between 1987-1989 averages and 1995 for three age groups: 70
      74, 75-80 (the control group that had no changes in requirements), and 81 and up.
      It does not appear that eliminating the road test for those ages 69 to 74 had any
      negative impact. On the contrary, it does not appear that the more frequent
      renewal period for those ages 81 and up produced any benefit compared to the
      control group. As the number of older drivers continue to increase into the
      future, the analysis of licensing requirements and their impact is important.

PMID- 9542547
TI  - The effect of resurfacing on friction, speeds and safety on main roads in
      Finland.
AB  - This study aimed at examining how resurfacing and the first winter period after
      resurfacing affect the safety of main roads in Finland. The study consisted of
      three substudies. In the first substudy the changes of side friction and lock
      braking friction were measured on newly paved roads after resurfacing and after
      the first winter period. The effect of different resurfacing methods was also
      compared in the course of the study. All the 50 road sections in the study were
      resurfaced in summer 1991 and measured with the friction truck of the Technical
      Research Centre of Finland (VTT). Friction was found to be highly dependent on
      the type of resurfacing treatment. In general, the friction of surfaces with high
      coefficients after resurfacing decrease and the lowest frictions increase with
      time, locked braking friction values immediately after resurfacing can be
      undesirably low. The second substudy dealt with the effect of resurfacing on the
      vehicle speeds. The analysis was based on automatic speed and weather measurement
      in 1991 and 1992 on resurfaced roads, which were resurfaced in the summer 1991
      and on a sample of comparison roads which had not been resurfaced. There is
      little change in speeds on the non-resurfaced roads during the study period, but
      there is some indication that resurfacing increases the average speeds, at least
      when the road is dry. Complete data were available for only one site, where the
      result was that average speeds on dry roads increased after resurfacing by 0.6
      km/h and increased still more (by 0.5 km/h) after the first winter period. The
      third substudy analysed fatal and injury accidents reported to the police on the
      resurfaced and comparison roads one and two years before, the same year
      resurfacing was performed and one and two years after the resurfacing. The
      accident results were similar to the speed findings. The most likely effect is a
      risk increase immediately after resurfacing by somewhat less than 7% and of 3 to
      7% of the first winter period. These results are, however, subject to large
      uncertainty because of the small number of accidents on the treatment roads.

PMID- 9542548
TI  - Fatalities from non-use of seat belts and helmets in Greece: a nationwide
      appraisal. Hellenic Road Traffic Police.
AB  - It has been established that seat belt use by car occupants and helmet use by
      motorcycle riders substantially reduces the risk of serious and fatal injuries
      following accidents. No study, however, has evaluated the motor vehicle deaths
      that could be prevented in Greece by general use of these devices, even though
      this country has the highest mortality from motor vehicle accidents in the
      European Union. We have estimated the odds ratios (OR) for death rather than
      injury in a motor vehicle accident by seat belt use among occupants of passenger
      cars or helmet use among motorcycle riders, using a nationwide database in which
      persons killed or injured in road traffic accidents in 1985 and 1994 were
      recorded. The study base included 910 dead and 19,511 injured persons for 1985
      and 1203 dead and 22,186 injured persons for 1994. The OR and 95% confidence
      intervals (CI) for death rather than injury was 0.69 (CI: 0.58 to 0.81, p < 10(
      5)) for seat belt users versus non-users and 0.64 (CI: 0.51 to 0.81; p < 10(-3))
      for helmet users versus non-users. There was evidence that the protective effect
      of these passive safety devices increased from 1985 to 1994 probably reflecting
      technological improvements. The proportion of all deaths that could have been
      avoided if all car occupants used seat belts was estimated to 27%, whereas 38% of
      motorcycle deaths could have been avoided if all motorcycle riders used helmets.
      These proportions translate to about 500 deaths per year, mostly deaths among
      young men.

PMID- 9542549
TI  - The assured clear distance ahead rule: implications for nighttime traffic safety
      and the law.
AB  - The assured clear distance ahead (ACDA) rule holds the operator of a motor
      vehicle responsible to avoid collision with any obstacle that might appear in the
      vehicle's path. Although widely considered a fundamental responsibility of safe
      driving, the ACDA rule is routinely violated by most drivers under nighttime
      conditions. This fact does not necessarily imply reckless disregard for public
      safety, however. Rather the troublesome discrepancy between drivers' behavior and
      the principles of safe driving may be understood in terms of vehicle operators'
      lack of awareness of selective losses of visual function that occur in low light.
      This theoretical perspective holds basic implications both for traffic
      regulations and for assessment of liability in nighttime road accidents.

PMID- 9542550
TI  - Are road safety evaluation studies published in peer reviewed journals more valid
      than similar studies not published in peer reviewed journals?
AB  - The peer review system of scientific journals is commonly assumed to prevent
      seriously flawed research from getting published. This paper compares the quality
      of 44 road safety evaluation studies published in peer reviewed journals to the
      quality of 79 evaluation studies dealing with the same safety measures, but not
      published in peer reviewed journals, in terms of seven criteria of study
      validity. Studies were scored for validity in terms of (1) sampling technique,
      (2) total sample size, (3) mean sample size for each result, (4) specification of
      accident or injury severity, (5) study design, (6) number of confounding factors
      controlled and (7) number of moderator variables specified. Confounding factors
      are all factors that disturb the attribution of a causal relationship between the
      safety measure being evaluated and the observed changes in safety, moderator
      variables are all variables that influence the size of the effect of the safety
      measure. Very few statistically reliable differences in study validity were found
      between studies published in peer reviewed journals and studies not published in
      such journals. There was, at best, a weak tendency for studies published in peer
      reviewed journals to score higher for validity. An interaction was found between
      author affiliation and type of publication with respect to study validity.
      Studies published in peer reviewed journals by authors who were at a university
      scored highest for validity. For a number of reasons, this study must be regarded
      as exploratory and its results as indicative only. The study does, however, point
      to a line of research that might be worth pursuing in larger and more rigorous
      studies.

PMID- 9542551
TI  - The occupations of drink drivers: using occupational information to identify
      targetable characteristics of offenders.
AB  - Data collected by the Victoria Police at the time an alleged drink-driving
      offender undergoes an evidential breath test for the presence of alcohol were
      analyzed to investigate the possibility that occupational information could be
      used to define groups of drink-drivers with similar characteristics. Such groups
      could then be utilized in the development of targeted public education campaigns
      in the Victorian (Australia) context where there are already high levels of
      enforcement and mass-media publicity. It is argued that drink-drivers in this
      context are likely to share some characteristics which might reduce the impact of
      current programs. Analysis of the data relied on the application of a theory of
      the relationship between career choice and other behavioral characteristics
      (Holland, 1973, Making Vocational Choices, Prentice Hall, Englewood Cliffs, N.J.;
      Holland, 1975, Manual for the Vocational Preference Inventory, Consulting
      Psychologists Press, Palo Alto, CA). The analysis identified two potential groups
      which accounted for 58% of the male drink-drivers. These groups differed from
      other male drink drivers in a number of ways, underlining the potential for their
      use as targets in future campaigns. One occupational category accounted for 42%
      of the male drink drivers, including occupations such as carpenter, electrician,
      chef, mechanic, gardener, and laborer. The behavioral characteristics associated
      with these occupational codes in the Holland model included asocial, conforming,
      reserved, introspective, unpopular, orderly, careful, unimaginative, and
      defensive. The other occupational category accounted for 16% of the male drink
      drivers and included occupations such as business manager, company director,
      public servant, and sales representative. Behavioral characteristics associated
      with this combination included acquisitive, adventurous, ambitious, energetic,
      extroverted, friendly, and generous.

PMID- 9542552
TI  - Lowering the legal blood alcohol level for motorcyclists.
AB  - The blood alcohol concentrations (BAC) of all operators involved in motorcycle
      accidents (MCA) and drivers of motor vehicle accidents (MVA) admitted to a New
      Jersey Level I Trauma Center during 1992 (the first year such data were
      computerized) were evaluated. Comparable to other institutional statistics (one
      third of vehicular accidents are related to alcohol consumption) our data showed
      13 (33%) of 40 MCA operators and 117 (35%) of 340 MVA drivers had measurable BAC.
      These values, as well as their respective Injury Severity Scores (ISS), were
      recorded and compared for significance of apparent differences using the 't' test
      for unpaired observations. Mean BAC was 124 +/- 24 (SE) mg dl-1 for MCA and 180
      +/- 9 mg dl-1 for MVA (p < 0.05). The respective mean ISS for MCA was 13.1 +/-
      5.4 and MVA was 7.9 +/- 0.9 (p = 0.12). These data indicate that drivers involved
      in MVA and MCA are frequently under the influence of alcohol. The mean BAC for
      motorcyclists is significantly less than that for drivers of four-wheeled
      passenger vehicles and is likely to reflect the need for greater coordination and
      balance when operating a two-wheeled vehicle.

PMID- 9542553
TI  - Does epidural analgesic technique influence mode of delivery?

PMID- 9542554
TI  - Obstetric outcome following epidural analgesia with bupivacaine-adrenaline 0.25%
      or bupivacaine 0.125% with sufentanil--a prospective randomized controlled study
      in 1000 parturients.
AB  - BACKGROUND: Epidural analgesia (EDA) is the most efficient method for pain relief
      during labour, but there is still a debate as to whether it interferes with the
      normal process of delivery. Some authors argue that the incidence of instrumental
      deliveries, Caesarean section, malrotation and protracted labour is increased in
      parturients receiving EDA. METHODS: 1000 parturients were prospectively
      randomized to receive EDA either with a high dose of local anaesthetic (0.25%
      bupivacaine with adrenaline = HD) or with a low dose (0.125% bupivacaine with
      sufentanil 10 micrograms = LD). RESULTS: The incidence of instrumental delivery
      and Caesarean section and the need for oxytocin was reduced in the LD compared to
      HD group. The delivery time was similar with HD and LD among primiparous, but
      decreased significantly among multiparous in the LD group. The incidence of
      malrotation was low in both groups. The quality of analgesia was equal during the
      first stage in the 2 groups, but was lower in the LD group during the second
      stage. More parturients in the LD group ambulated, but this did not affect the
      incidence of instrumental delivery. CONCLUSION: It is concluded that a lower
      dosage of bupivacaine combined with sufentanil in epidural analgesia
      significantly improves the obstetric outcome as compared to a higher dosage of
      bupivacaine with adrenaline using intermittent bolus technique.

PMID- 9542555
TI  - Efficacy of propacetamol in the treatment of postoperative pain. Morphine-sparing
      effect in orthopedic surgery. Italian Collaborative Group on Propacetamol.
AB  - BACKGROUND: Combined analgesic regimens have been suggested to improve the
      treatment of postoperative pain. The aim of our study was to evaluate the
      analgesic efficacy and tolerability of propacetamol, in combination with
      morphine. METHODS: Four i.v. infusions of propacetamol 2 g or placebo were
      administered, in a double-blind fashion, after orthopedic surgery (n = 97).
      Morphine was administered by a patient-controlled analgesia (PCA) device. The
      total dose of morphine, pain intensity and global efficacy of treatment were
      evaluated. Tolerability was assessed by monitoring blood pressure, heart and
      respiratory rate, sedation scores, adverse events, and renal and hepatic
      parameters. RESULTS: The total dose of morphine was significantly decreased in
      the propacetamol group compared to placebo (9.4 +/- 8.5 mg vs 17.6 +/- 12 mg; P <
      0.001), arriving at a sparing effect of 46%. The evolution of pain intensity
      showed a similar pattern in the two groups. Global efficacy of treatment was
      rated significantly better by patients receiving the combination propacetamol +
      PCA morphine (87% of "good"/"excellent" ratings vs 65%; P = 0.01). Tolerability
      was comparable in the two groups. Eight patients in the propacetamol and 4
      patients in the placebo group reported adverse events, of mild/moderate
      intensity, most commonly nausea/vomiting. Renal and hepatic parameters were also
      seen to be comparable. CONCLUSION: These results confirm a significant morphine
      sparing effect, significantly better scores in the final assessment by patients,
      and a good tolerability of propacetamol after orthopedic surgery. The drug may,
      therefore, represent a useful alternative to NSAIDs, as complementary drug to
      opioids, in the management of moderate/severe postoperative pain.

PMID- 9542556
TI  - Preoperative adjuvant epidural tramadol: the effect of different doses on
      postoperative analgesia and pain processing.
AB  - BACKGROUND: Tramadol is an analgesic with combined opioid agonist and monoamine
      reuptake blocker properties, which may be useful as a perioperative analgesic and
      antinociceptive adjuvant. METHODS: The dose-dependent effects of adjuvant
      preoperative epidural tramadol on postoperative analgesia (pain scores and
      patient-controlled analgesia (PCA) use) and pain processing (heat pain
      thresholds) were prospectively studied in a double-blind, randomised, placebo
      controlled 5-day trial. Forty patients undergoing knee or hip surgery received
      anaesthesia with epidural lidocaine and epidural tramadol 20, 50 or 100 mg or
      placebo as a preoperative adjuvant. Postoperative analgesia was by intravenous
      PCA tramadol in all patients. RESULTS: Postoperative pain scores were similar in
      all groups. The time to first PCA use was shorter, the total dose and duration of
      PCA use greater, and side-effects more common with 20 mg tramadol than with 100
      mg or placebo (P < 0.05). There were no differences in PCA doses required or side
      effects between the tramadol 100 mg and placebo treatment groups. Heat pain
      tolerance thresholds were increased with 100 mg tramadol at 48 h postoperatively
      compared to baseline and placebo (P = 0.01). CONCLUSIONS: Preoperative adjuvant
      epidural tramadol does not improve postoperative analgesia after lidocaine
      epidural anaesthesia compared to placebo. Tramadol 20 mg results in anti
      analgesia and increased side-effects. While tramadol 100 mg depresses
      postoperative pain-processing, as measured by heat pain tolerance thresholds,
      this is not reflected in improved clinical pain measures.

PMID- 9542557
TI  - Plasma levels of clonidine following epidural bolus injection in children.
AB  - BACKGROUND: The use of clonidine as an adjunct to epidural administration of
      local anesthetics in children has been reported to substantially improve the
      duration and quality of postoperative analgesia. The aims of the present study
      were to determine the pharmacokinetic profile and to investigate the interaction
      between postoperative sedation and analgesia after epidurally administered
      clonidine in children. METHODS: Plasma levels of clonidine (0-10 h postop) and
      assessment of postoperative analgesia and sedation (0-24 h postop) were performed
      at predetermined intervals following lumbar epidural administration of
      bupivacaine 2.0 mg/kg and clonidine 2 mg/kg in 8 children undergoing ureteral re
      implantation surgery using general anesthesia (age range: 1-9 yr, weight range: 9
      41 kg). Plasma levels of clonidine were analyzed by radioimmunoassay, and
      sedation and analgesia were assessed by previously described scoring systems.
      RESULTS: The venous plasma pharmacokinetics of clonidine following epidural
      administration showed a considerable interindividual variation. Cmax and Tmax
      values of clonidine were found to be within the 0.45-0.77 ng/mL and 48-193 min
      range, respectively. The time to absorb 95% of the clonidine dose from the
      epidural space into plasma varied between 36 min and 7.6 h. In 6 of the 8
      patients postoperative analgesia substantially outlasted the duration of sedation
      (> or = 2 h). Sedation could not be detected in any patients at plasma
      concentrations below 0.3 ng/mL. CONCLUSIONS: The pharmacokinetic profile
      associated with epidural clonidine administration in children (1-9 y) was similar
      to that previously reported in adults. The postoperative analgesia seen after
      administration of epidural bupivacaine-clonidine during general anesthesia in
      children cannot only be explained by residual postoperative sedation.

PMID- 9542558
TI  - Granisetron prevents nausea and vomiting during spinal anaesthesia for caesarean
      section.
AB  - BACKGROUND: Nausea and vomiting during spinal anaesthesia for caesarean section
      are common and unpleasant complications. This study was undertaken to evaluate
      the efficacy of granisetron, a selective 5-hydroxytryptamine type 3 receptor
      antagonist, for prophylactic treatment of nausea and vomiting in parturients
      undergoing nonemergent caesarean section under spinal anaesthesia. METHODS: In a
      randomized, double-blind, placebo-controlled trial, 100 patients, 21-38 years,
      received either placebo (saline) or granisetron at 3 different doses (20
      micrograms.kg-1, 40 micrograms.kg-1 or 80 micrograms.kg-1) (n = 25 for each)
      intravenously immediately after clamping of the foetal umbilical cord. Nausea,
      vomiting and safety assessments were performed during spinal anaesthesia for
      caesarean section. RESULTS: The treatment groups were similar with regard to
      maternal characteristics and operative management. The incidence of nausea and
      vomiting was 64%, 52%, 14% and 12% after administration of placebo and
      granisetron in a dose of 20 micrograms.kg-1, 40 micrograms.kg-1 and 80
      micrograms.kg-1, respectively (P < 0.05; overall Fisher's exact probability
      test). No clinically important adverse effects were observed in any group.
      CONCLUSION: Prophylactic use of granisetron in a minimum dose of 40 micrograms.kg
      1 is effective for preventing nausea and vomiting during spinal anaesthesia for
      caesarean section.

PMID- 9542559
TI  - Operations on patients deemed "unfit for operation and anaesthesia": what are the
      consequences?
AB  - BACKGROUND: The decision "patient unfit for anaesthesia and operation" is likely
      to cause a delay of the scheduled operation. This retrospective evaluation was
      done: 1) to determine the correctness of preoperative tentative diagnoses of
      coexisting diseases making anaesthesia and operation excessively risky in
      relation to the physician's training status; 2) to examine the question of
      whether preoperative medical management modified according to the
      anaesthesiologist's suggestions had a positive impact on the perioperative
      course. METHODS: The medical records of patients scheduled for elective non
      cardiac surgery who were rated "unfit for operation and anaesthesia" were
      evaluated. The accuracy of the tentative diagnoses was examined for relation to
      the training status of the anaesthesiologists. The preoperative management was
      tested for its impact on postoperative outcome. RESULTS: During the observation
      period 16,122 patients underwent preoperative anaesthesiological assessment; 1021
      (6.3%) were initially considered to be unfit for operation and anaesthesia. The
      records of 807 patients were available for review. The accuracy of the tentative
      diagnoses was 70%, and was not significantly affected by the training status of
      the physicians (P = 0.022). Four hundred and seventeen patients were excluded
      from the second part of the investigation (discharged without operation,
      underwent operation using local anaesthesia or tentative diagnosis not
      confirmed). Three hundred and ninety patients were operated under general
      anaesthesia. Group I (n = 216) was managed according to the anaesthesiologist's
      suggestions and was found to have a significantly lower complication rate (18.1%)
      than group II (n = 174) in which the suggestions from the preoperative assessment
      were ignored (32.2%; P < 0.05). The perioperative mortality rate in group I was
      2.3% compared with 5.2% in group II (n.s.; P > 0.05). CONCLUSIONS: We conclude
      that the anaesthesiology decision "patient unfit for operation and anaesthesia"
      has a high accuracy, independent of the anaesthesiologist's training status, and
      that preoperative medical management significantly reduces complications.

PMID- 9542560
TI  - Pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine.
      A comparison of two injection sites.
AB  - BACKGROUND: Intramuscular scopolamine plus morphine premedication is
      traditionally used when prominent sedative or antisialogogue effect is needed.
      Knowledge of the pharmacokinetics of scopolamine is limited due to low plasma
      concentrations found after therapeutic doses. This investigation compares the
      pharmacokinetics and the clinical responses of this drug combination injected
      into two commonly used injection sites. METHODS: Twelve ASA class 1 patients
      scheduled for minor surgery under spinal anaesthesia received scopolamine 6
      micrograms/kg plus morphine 200 micrograms/kg injected in either deltoid (group
      D, n = 6) or gluteal (group G, n = 6) muscle. RESULTS: The peak plasma
      concentrations of scopolamine after deltoid or gluteal injection (2.2 vs 1.6
      micrograms/l) and the time they were reached (17 vs 19 min) were comparable. The
      absorption of morphine was similar in both groups (Tmax 16 min), but the peak
      plasma concentrations were higher after deltoid injection (71 vs 49
      micrograms/l). The individual variation in the elimination half-lives of both
      scopolamine and morphine was smaller after deltoid injection (T1/2 scopolamine
      1.9 +/- 0.7 vs 2.1 +/- 1.1 h, morphine 1.3 +/- 0.7 vs 2.3 +/- 1.5 h). Moderate
      slowing (25%) of heart rate was found in both groups. A heavy sedation and
      antisialogogue effect (VAS) was found in both groups with faster occurrence of
      maximal effect in group D (60 vs 120-180 min). CONCLUSION: More predictable
      pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine
      premedication can be achieved after an injection into deltoid muscle.

PMID- 9542561
TI  - Improved oxygenation using the prone position in patients with ARDS.
AB  - BACKGROUND: The prone position is known to increase oxygen uptake in patients
      with Adult Respiratory Distress Syndrome (ARDS). METHODS: In this clinical study
      from 1995-96, 14 ARDS patients with severe respiratory failure were treated for
      at least 1 h in the prone position. Responders, defined as having more than 10%
      increase in PaO2/FiO2 ratio from baseline after 1 h, were treated at least 6 h in
      the prone position. RESULTS: 11 patients responded during the first period of the
      prone position (primary responders). Two of the 3 non-responders were turned
      prone a second time with increase in the PaO2/FiO2 ratio (secondary responders).
      Mean PaO2/FiO2 ratio (mean +/- SEM) in the supine position was 11.7 +/- 0.8 kPa,
      increasing to 16.6 +/- 1.8 kPa and 18.0 +/- 1.4 kPa after 1 and 6 h respectively
      (P = 0.009). Mean time spent in the prone position was 69 h (range 3-256 h), and
      mean ventilatory time was 17 d (3-52 d). The mortality in this subgroup of our
      patients with ARDS was 42%, compared to 58% in 19 patients not turned prone in
      the same period. CONCLUSION: The prone position together with PEEP appears to
      improve ventilation-perfusion matching. The prone position is simple, effective
      and readily available and could be used early in most patients with ARDS.

PMID- 9542562
TI  - Reduced CO2-elimination during combined high-frequency ventilation compared to
      conventional pressure-controlled ventilation in surfactant-deficient piglets.
AB  - BACKGROUND: Combined high-frequency ventilation (CHFV) combines a conventional
      low-frequency component with super-imposed high-frequency jet pulses. The
      intention is to overcome the limited CO2-elimination of high-frequency
      ventilation, and to decrease airway pressures and enhance hemodynamic performance
      by reducing the conventional component. The present study was performed to
      compare the effects of conventional continuous positive-pressure ventilation
      (CPPV) on gas exchange, airway pressures and cardiac output to those of CHFV at
      matched minute volume (MV) and mean airway pressure (MPAW). METHODS: Sixteen
      anaesthetised piglets with lavage-induced surfactant deficiency were ventilated
      with CPPV, with positive end-expiratory pressure (PEEP) set to obliterate the
      lower inflection point of the inspiratory pressure-volume loop. This setting was
      compared to CHFV during which 50% of the total MV was applied as superimposed jet
      pulses of 20 Hz at otherwise unchanged settings, and to CPPV at a PEEP level
      which was reduced (CPPVred) until MPAW matched MPAW during CHFV. Gas exchange,
      airway pressures and hemodynamics were measured after the ventilatory setting had
      been applied for 20 min. RESULTS: MPAW decreased from (median) 2.7 kPa with CPPV
      to 2.4 kPa with CHFV (P < or = 0.05). Peak inspiratory pressure was 3.6 kPa with
      CPPV, 3.2 kPa with CHFV, and 3.2 kPa with CPPVred (P < or = 0.05 for differences
      to CPPV), respectively. PaCO2 was comparable during CPPV (5.9 kPa), CPPVred and
      CHFVCO2, while it increased during CHFV (6.8 kPa, (P < or = 0.05)). Cardiac
      output did not differ significantly between the settings. CONCLUSION: In the
      porcine lavage model, CO2-elimination is reduced during CHFV compared to CPPV at
      matched minute volume. At matched mean airway pressure, CHFV fails to reduce peak
      inspiratory airway pressure and to improve hemodynamic performance compared to
      CPPV.

PMID- 9542563
TI  - Plasma catecholamines and haemodynamic changes during pneumoperitoneum.
AB  - BACKGROUND: Insufflation of CO2 into the abdomen is used during all kinds of
      laparoscopic operations. The procedure elicits haemodynamic and hormonal
      responses. The reports on sympathetic responses to laparoscopic surgery have been
      conflicting. However, few studies have assessed sympathetic and haemodynamic
      responses to CO2 insufflation per se, eliminating possible effects of intubation,
      skin incision, surgical manipulation and positioning of the body. No studies have
      measured both venous and arterial plasma catecholamines, the latter being a more
      sensitive indicator of sympathetic activity. In the present study, we
      hypothesised an increased sympathetic activity during pneumoperitoneum and an
      association between haemodynamic and sympathetic responses. METHODS: Plasma
      adrenaline and noradrenaline from the radial artery and superior vena cava were
      measured immediately before and 10 min after abdominal insufflation of CO2 in 11
      subjects. Haemodynamics were monitored invasively. RESULTS: During
      pneumoperitoneum arterial plasma noradrenaline increased from 155 (106, 209)
      pg/ml (median, lowest and highest quartile) to 283 (188, 378) pg/ml (P = 0.003),
      while there were no changes in arterial plasma adrenaline. The calculated
      arterial-superior vena cava difference in plasma noradrenaline did not change,
      indicating no increased sympathetic activity in the drainage area of the superior
      vena cava. Heart rate and cardiac index were unchanged, while total peripheral
      resistance and mean arterial blood pressure increased (P = 0.002). The changes in
      arterial plasma noradrenaline were closely related to the changes in total
      peripheral resistance (r = 0.69, P = 0.01). CONCLUSIONS: Plasma noradrenaline
      increases during pneumoperitoneum and is associated with changes in total
      peripheral resistance. Plasma adrenaline is unchanged and there is no evidence of
      increased sympathetic outflow to the drainage area of the superior vena cava.
      Thus, the increase in plasma noradrenaline may be due to more local activation of
      the sympathetic nervous system, probably somewhere from the drainage area of the
      inferior vena cava.

PMID- 9542564
TI  - Forced-air surface warming versus oesophageal heat exchanger in the prevention of
      peroperative hypothermia.
AB  - BACKGROUND: In a prospective, randomized, placebo-controlled study we
      investigated the efficacy of 2 different heating methods in 24 patients
      undergoing abdominal surgery of at least 2 h expected duration. METHODS: Group I:
      control, no active warming. Group II: forced-air surface warming on upper
      extremities and upper thorax. Group III: warming with oesophageal heat exchanger.
      All patients had a standardized, combined general and epidural anaesthesia. Core
      and skin temperatures were measured at induction of general anaesthesia, and
      subsequently every 30 min, and changes in total body temperature were calculated.
      RESULTS: There were no statistically significant differences between the 3 groups
      regarding demographic data. Patients in groups I and III developed hypothermia,
      while this was not the case with patients in group II. When using analysis of
      variance with repeated measurements, there was no significant difference in core
      temperature, comparing group I and group III (P = 0.299) or the interaction
      between time and treatment of these groups (P = 0.373). As a consequence, data
      from groups I and III were pooled and regarded as an internal group on the one
      hand, and group II as an external group on the other hand. Core temperature, the
      mean skin temperature and total body temperature were significantly different
      comparing the internal group and the external group. The interaction between time
      and treatment was likewise found to be significantly different. CONCLUSION: We
      conclude that in major abdominal procedures lasting 2 h or more, serious
      hypothermia develops unless effective measures to prevent hypothermia are used.
      Forced-air warming of the upper part of the body is effective in maintaining
      normothermia in these patients, while central heating with an oesophageal heat
      exchanger, at least in its present form, does not suffice to prevent hypothermia.

PMID- 9542565
TI  - Effects of desflurane, sevoflurane and halothane on postinfarction spontaneous
      dysrhythmias in dogs.
AB  - BACKGROUND: Although desflurane (DES) and sevoflurane (SEV) have desirable
      features for use in patients with coronary artery disease, their effects on
      ventricular dysrhythmias following infarction are less known. We therefore
      examined the effects of DES and SEV upon spontaneous postinfarction ventricular
      dysrhythmias in dogs, and compared those effects to the well-established
      antidysrhythmic effects of halothane (HAL) in this model. METHODS: After
      institutional approval, the left anterior descending coronary artery was ligated
      in 16 adult mongrel dogs during isoflurane anesthesia. All dogs developed acute
      myocardial infarction and severe ventricular tachydysrhythmias. Twenty-two hours
      after infarction, dogs were anesthetized at 1.5 MAC with desflurane (10.8%)
      followed by sevoflurane (3.5%) in the treatment group (n = 10), or halothane
      (1.3%) in the other group (n = 6). Anesthetic gases were allowed to equilibrate
      for at least 20 min at each end-tidal concentration. At this time, the ECG was
      recorded for 9 min and evaluated for the number of ventricular ectopic and
      sinoatrial beats and summed duration of ventricular tachycardia. RESULTS: DES and
      SEV reduced the average rate of total ventricular ectopic beats by 40 +/- 4% and
      42 +/- 4%, respectively. HAL decreased total ventricular ectopic rate by 59 +/-
      6% and 62 +/- 5% after durations of anesthesia comparable to DES and SEV,
      respectively. Decreases in dysrhythmia in the presence of DES and SEV were
      significantly smaller than those produced by HAL after a comparable total
      duration of anesthesia. CONCLUSION: DES and SEV inhibit spontaneous
      postinfarction ventricular dysrhythmias, although attenuation of dysrhythmias was
      smaller than the inhibition during comparable doses of HAL.

PMID- 9542566
TI  - Effects of inhaled nitric oxide on platelet-activating factor-induced pulmonary
      hypertension in dogs.
AB  - BACKGROUND: Platelet-activating factor (PAF), a lipid mediator released during
      endotoxin shock, induces pulmonary hypertension, systemic hypotension and cardiac
      dysfunction. In this study, we compared the effect of inhaled nitric oxide (NO)
      on PAF-induced pulmonary hypertension and NO metabolism with that on pulmonary
      hypertension induced by a stable thromboxane A2 mimetic, U46619. Since PAF
      induced hypotension might be mediated by NO, the effect of inhaled NO combined
      with an intravenously administered NO synthase inhibitor, NG-nitro-L-arginine (L
      NNA), on PAF-induced hemodynamic change was also investigated. METHODS: In a
      total of 28 beagles anesthetized with pentobarbital the following substances were
      intravenously administered: PAF 0.56 +/- 0.30 microgram.kg-1.min-1 (group PAF), L
      NNA 10 mg.kg-1 + PAF 0.04 +/- 0.03 microgram.kg-1.min-1 (group L-NNA + PAF),
      U46619 0.60 +/- 0.11 microgram.kg-1.min-1 (group U46619) or L-NNA 10 mg.kg-1 +
      U46619 0.61 +/- 0.23 microgram.kg-1.min-1 (group L-NNA + U46619) to obtain a mean
      pulmonary arterial pressure (MPAP) of 25 mmHg. Nitric oxide was then inhaled at
      5, 10, 20 and 40 ppm for 15 min at 15-min intervals in the order of increasing
      concentration. An additional 7 dogs (control group) inhaled NO at normal MPAP (17
      mmHg). Hemodynamic and respiratory parameters, NOHb, NO2- + NO3-, and MetHb
      levels in blood were measured before and during NO administration. RESULTS: In
      the control group, hemodynamic and respiratory values did not change
      significantly during NO administration. In group PAF, NO significantly reversed
      the PAF-induced pulmonary hypertension. PAF induced a marked systemic hypotension
      and cardiac output reduction, but these changes were not affected by inhalation
      of NO. L-NNA pretreatment markedly decreased the dose of PAF required to maintain
      a MPAP of 25 mmHg, and abolished the PAF-induced hypotension. In group L-NNA +
      PAF, the diminishing effect of inhaled NO on pulmonary vascular resistance (PVR)
      was significantly greater than that in group PAF. U46619 induced pulmonary
      hypertension and increases in blood pressure, intrapulmonary shunt and peak
      airway pressure. L-NNA pretreatment did not change the dose of U46619 required to
      maintain a MPAP of 25 mmHg. The effects of inhaled NO on PVR decrease were
      similar in groups U46619 and L-NNA + U46619. No NOHb was detected in any group.
      NO2- + NO3- concentration increased during NO administrations. There were no
      significant differences in NO2- + NO3- concentration among groups. CONCLUSIONS:
      Inhaled NO at the dose of 5-40 ppm effectively reversed PAF-induced pulmonary
      hypertension, especially following pretreatment with L-NNA. Inhaled NO did not
      affect PAF-induced hypotension or cardiac dysfunction. These findings indicate
      that low concentrations of inhaled NO may be useful in reversing pulmonary
      hypertension in the endotoxemia where PAF may be one mediator.

PMID- 9542567
TI  - The end-systolic pressure-volume relationship and ventriculoarterial coupling in
      patients undergoing coronary artery bypass graft surgery.
AB  - BACKGROUND: The end-systolic pressure-volume relationship and analysis of
      ventriculoarterial coupling have been established as a useful tool to determine
      the left ventricular performance and arterial loading conditions. The purpose of
      this study was to evaluate the end-systolic pressure-volume relationship and
      ventriculoarterial coupling in anesthetized patients with either a normal heart
      or coronary artery disease (CAD) using a transesophageal echocardiography (TEE)
      monitor. METHODS: Sixteen patients with CAD and 4 patients without ischemic
      disease were studied. The end-systolic volume of the left ventricle was obtained
      by TEE, and the end-systolic pressure was obtained from the brachial arterial
      dicrotic pressure. In order to obtain the end-systolic pressure-volume
      relationship, we plotted 7 different left ventricular end-systolic pressures
      against the corresponding left ventricular end-systolic volumes during the
      pressure manipulation. The linear regression obtained by this method was
      designated as the end-systolic elastance (Ees). Furthermore, we calculated the
      effective arterial elastance (Ea) using the pressure-volume framework. RESULTS:
      We divided the patients with CAD into 3 groups: Group A: left ventricular
      ejection fraction (LVEF) > 50%, Group B: LVEF 35-50%, Group C: LVEF < 35%. We
      also studied a control group (Group D) who did not suffer from an ischemic heart
      condition. Ees in group C (1.4 +/- 0.2) was lower than in the other 3 groups (P <
      0.05). Ea/Ees in group C (1.9 +/- 0.1) was greater than in group A (0.7 +/- 0.1),
      group B (1.0 +/- 0.06) and group D (0.6 +/- 0.1)(P < 0.05). There were no
      significant differences in Ees and Ea/Ees between group A and group D.
      CONCLUSIONS: We found that patients with CAD and a normal LVEF had a
      physiological Ea/Ees identical to the control subjects. We also demonstrated that
      patients with CAD and a reduced LVEF showed a deterioration in Ea/Ees.

PMID- 9542568
TI  - Transient radicular irritation with intrathecal plain lignocaine.
AB  - BACKGROUND: The aetiology of the syndrome known as transient radicular irritation
      (TRI) has generated much interest. METHOD: A 50-year-old woman had right knee
      arthroscopy performed under spinal anaesthesia with 1% plain lignocaine. RESULT:
      At home, on the night of the procedure, she was woken by severe, bilateral cramp
      like pain in both buttocks radiating to her thighs. Neurological examination of
      her lower limbs, the next morning, was entirely normal. The pain lasted for 36 h
      and a full recovery was made. CONCLUSION: This case of transient radicular
      irritation occurred in a patient given 40 mg of subarachnoid lignocaine (the
      lowest dose of isobaric preservative-free lignocaine reported thus far that has
      been associated with these symptoms). Her operation was performed in the supine
      position. The lack of confounding factors (hyperbaricity, high concentration
      solution, preservatives, lithotomy position) suggests lignocaine as a possible
      cause, yet current theories do not fully explain the aetiology of transient
      radicular irritation. Results from large-scale epidemiological studies will
      hopefully provide insight into the cause of this problem.

PMID- 9542569
TI  - Combined overdose with verapamil and atenolol: treatment with high doses of
      adrenergic agonists.
AB  - A 55-year-old man was admitted following an overdose of sustained-release
      verapamil (calcium channel blocker) and ordinary-release atenolol (beta-1
      blocker). At admission, there was extreme bradycardia (20-25 beats min-1) and
      hypotension (systolic arterial pressure 40-50 mm Hg). To counteract the
      cardiovascular depression, prenalterol, dopamine, dobutamine, isoprenaline,
      adrenaline and noradrenaline were used. A satisfactory state was obtained with
      adrenaline, noradrenaline and dopamine infused at high rates. Cardiac output was
      then more than 101 min-1, with a very low total peripheral resistance. The
      infusion of the adrenergic agonists could be interrupted on day 3. Prolonged
      ventilator treatment was necessary but the patient recovered without sequelae.
      Treatment options for similar cases are outlined.

PMID- 9542570
TI  - When fiberoptic bronchoscopy is indicated in the management of postoperative
      atelectasis.

PMID- 9542571
TI  - Calculated versus measured oxygen consumption during and after cardiac surgery.
      Is it possible to estimate lung oxygen consumption?

PMID- 9542572
TI  - Tracheal adrenaline in infants.

PMID- 9542573
TI  - Some electrocardiographic patterns predicting sudden cardiac death that every
      doctor should recognize.
AB  - In recent years major advances have been made in the recognition and treatment of
      candidates to sudden cardiac death. These advances include very sophisticated
      diagnostic and therapeutic techniques, such as genetic testing and the
      implantable cardioverter-defibrillator, new knowledge coming from large
      multicenter trials, particularly about the poor efficacy of so-called
      "antiarrhythmic" drugs, but also very important advances have been made in
      improving the diagnostic value of simple techniques such as the twelve-lead
      electrocardiogram. In this article six different electrocardiographic patterns
      associated to sudden cardiac death are described. Some patterns, like left
      ventricular hypertrophy or low voltage in the limb electrocardiographic leads,
      are frequent and the incidence of sudden death in these patients is relatively
      low, although clearly higher as compared to individuals with a normal
      electrocardiogram. On the other hand, other patterns which are rarer (like the
      long QT syndrome or the syndrome of right bundle branch block and ST segment
      elevation in V1-V3) are associated to a very high rate of sudden death. Because
      sudden death can be prevented in many cases, every doctor should be able to
      recognize these types of electrocardiograms.

PMID- 9542574
TI  - Ambulatory blood pressure, nocturnal blood pressure reduction and plasma
      catecholamines.
AB  - OBJECTIVE AND DESIGN: Controversial data have been reported on plasma
      catecholamines in hypertensives. Aims of this study were to find whether 24-hour
      ambulatory blood pressure was correlated with circulating catecholamines and to
      investigate whether nocturnal blood pressure reduction was associated with
      baseline plasma catecholamines. Samples for catecholamine determination were
      obtained in 34 consecutive male subjects after a 30-minute rest and before
      ambulatory blood pressure monitoring. RESULTS: Hypertensive patients (n = 22; 24
      hour blood pressure: 145 +/- 14/94 +/- 6 mm Hg) showed similar norepinephrine and
      epinephrine levels when compared with normotensives (n = 12; 24-hour blood
      pressure: 124 +/- 6/81 +/- 6 mm Hg), and higher dopamine values (hypertensives:
      64.6 +/- 58; normotensives: 26.2 +/- 31 pg/ml; p < 0.05). A positive correlation
      was observed between dopamine and diastolic nocturnal blood pressure (p < 0.05)
      while a negative correlation was found between dopamine and nocturnal diastolic
      blood pressure reduction (p < 0.025). No significant relationship was observed
      between both norepinephrine and epinephrine, and 24-hour blood pressures.
      CONCLUSIONS: Since previous reports have documented malfunctioning of
      dopaminergic system in hypertension, the higher levels of circulating plasma
      dopamine found in hypertensive patients in the present study may account for a
      peripheral compensatory increase. The correlation between dopamine and nocturnal
      blood pressure fall seems to indicate that the impairment of dopaminergic system
      may influence the 24-hour blood pressure profile, affecting the nocturnal blood
      pressure reduction.

PMID- 9542575
TI  - A randomized, double-blind comparison of the antihypertensive efficacy and safety
      of once-daily losartan compared to twice-daily captopril in mild to moderate
      essential hypertension.
AB  - INTRODUCTION: The antihypertensive efficacy and safety of losartan, a specific
      and selective angiotensin II (AII) receptor antagonist, was compared to captopril
      in patients with mild or moderate essential hypertension. DESIGN: This
      multinational, randomized trial consisted of a 4-week single-blind, placebo
      baseline period followed by a 12-week double-blind, parallel comparison of once
      daily administration of losartan 50 mg or twice-daily administration of captopril
      25 mg. After 6 weeks of treatment, the daily dosage was doubled in patients whose
      sitting diastolic blood pressure (SiDBP) remained > or = 90 mm Hg. PATIENTS:
      Patients with essential hypertension having a mean trough SiDBP of 95-115 mm Hg
      after the placebo baseline period were randomized to losartan (N = 192) or
      captopril (N = 204) treatment. MAIN OUTCOME MEASURES: The primary efficacy
      variable was the mean change from baseline to Week 12 in trough SiDBP. Safety was
      assessed by recording spontaneously reported or observed adverse experiences and
      clinical laboratory measurements. RESULTS: After 12 weeks, both treatments
      produced clinically important reductions in trough SiDBP and sitting systolic
      blood pressure (SiSBP). These mean reductions (SiDBP, SiSBP) were significantly
      greater in the losartan group (-11.5 and -15.4 mm Hg, respectively) than in the
      captopril group (-9.3 and -12.2 mm Hg, respectively) (p = 0.010 for diastolic and
      p = 0.023 for systolic). The percentage of patients exhibiting an excellent
      (trough SiDBP < 90 mm Hg) or good (trough SiDBP > 90 mm Hg, with decrease of > or
      = 10 mm Hg) antihypertensive response to losartan and captopril therapy at Week
      12 was comparable (60.0% and 54.7%, respectively). The percentage of patients
      reporting a clinical adverse experience considered drug-related by the
      investigator was 13% in the captopril group and 10% in the losartan group. The
      incidence of drug-related cough was 2.6% in the losartan group and 4.4% in the
      captopril group. CONCLUSION: Once daily administration of losartan 50 to 100 mg
      is an effective treatment for patients with essential mild to moderate
      hypertension. The antihypertensive efficacy of losartan 50/100 mg is
      significantly greater than that of twice daily captopril 25/50 mg. Both
      treatments were generally well-tolerated. The number of patients with the side
      effect of cough was higher following captopril.

PMID- 9542576
TI  - BWGIC guidelines for training and quality control in adult interventional
      cardiology. Belgian Working Group of Invasive Cardiology.

PMID- 9542577
TI  - Lectin histochemistry of human leukaemic mast cells (HMC-1) transplanted into
      severe combined immunodeficient (scid) mice.
AB  - It is difficult to isolate and impossible to propagate human mast cells in tissue
      culture. As an alternative to the use of human differentiated mast cells, a human
      leukaemic mast cell line (HMC-1), which can be propagated in vitro, has been
      employed in a number of studies. Carbohydrate binding proteins, lectins, have
      been used to characterise the terminal sugar residues of human mast cells in
      situ. The aim of the present study is to characterise the lectin binding sites of
      HMC-1 cells transplanted into severe combined immunodeficient (scid) mice.
      Lectins specific for the complex carbohydrates, neuraminic acid and N
      acetylglucosamine residues showed generally a strong uniform binding pattern,
      whereas mannose and glucose specific yielded lectins a greater heterogeneity.
      This glycotope expression pattern has some similarities with those of human mast
      cells in situ, and therefore HMC-1 cells grown in scid mice constitute a valuable
      model system for the study of carbohydrate expression in human mast cells.

PMID- 9542578
TI  - Long-term action of potassium bromide on the rat thyroid gland.
AB  - Male rats fed by a standard diet with determined of bromine and iodine content
      were exposed to a 133-day oral administration of KBr (100, 200, 400 mg Br-/l
      drinking water). Their thyroid glands showed increased growth of the epithelial
      cells reflected by a microfollicular rearrangement of the parenchyma due to
      proliferation of very small follicles with a low or zero content of colloid.
      Morphometric analysis of thyroids of Br(-)-exposed animals revealed a significant
      decrease in the volume of intrafollicular colloid and marked increase in the
      number of the smallest follicles (areas up to 100 and 100-300 micron 2). In
      addition, the nuclei of thyrocytes showed an increased number of mitoses. The
      vascularization was increased as well. In the blood plasma of the Br(-)-exposed
      animals the T4 concentration was significantly decreased in dependence on the
      bromine concentrations. Thyroglobulin immunoreactivity in the colloid of Br(-)
      exposed animals decreased after administration of 400 mg Br-/l drinking water.
      Increasing concentrations of Br- in the drinking water caused an increased
      bromine concentration in the thyroid, a decreased iodine content and a decreased
      I/Br molar ratio. The changes in the rat thyroid caused by long-term
      administration of 100 mg Br-/l were similar to hyperplastic parenchymal goitre
      and were comparable to those induced in previous experiments by the same bromine
      concentration administered over a 16- and 66-day period respectively.

PMID- 9542579
TI  - Succinate dehydrogenase (SDH) activity in single Paramecium caudatum cells.
AB  - We measured in situ the activity of succinate dehydrogenase (SDH), one of the
      mitochondrial marker enzymes, in single Paramecium cells. SDH activity was
      detected with nitroblue tetrazolium (Nitro BT). Images of cells were captured
      every 30 sec at 590 nm, nearly the isosbestic wavelength of two reduction
      products of Nitro BT, by using a microphotometric system for image analysis.
      Activity was estimated by the slope of linear regression lines representing the
      relationship between total absorbance of the processed image and delta reaction
      time (real reaction time minus 30 sec). To investigate individual differences in
      Paramecium cell populations, SDH activity was measured in cells at various
      succinate concentrations. Paramecium SDH showed bimodal activity distribution
      patterns at three of four succinate concentrations tested. This result suggests
      that there are two groups of Paramecium populations with different SDH activity
      under control culture conditions. On the basis of the relationship between SDH
      activity and succinate concentration, mean Vmax and apparent Km values were
      estimated. A Km of 3.2 mM was found for Paramecium.

PMID- 9542580
TI  - Region- and age-dependent variations of muscle fibre properties.
AB  - The cytophotometric-morphometrical analysis of extensor digitorum longus and
      soleus muscles of 2.5 and 18 months old rats revealed regional and age-dependent
      differences in fibre type distribution, fibre area and fibre type related-enzyme
      activities which characterize contractility and metabolic profile. Variations
      along the longitudinal axis from the origin to the insertion and along three
      transversal axes from superficial to deep were found dependent on the muscle
      investigated. For example, the fibres of extensor digitorum longus muscle showed
      increased contractile and glycolytic capacities near insertion and the fibres of
      soleus muscle increased oxidative capacity in its middle part. Furthermore, the
      contribution of the fibre type that is dominant in a muscle (fast-glycolytic
      fibre type in extensor digitorum longus and slow-oxidative fibre type in soleus
      muscle) to the total number of fibres increased from origin to insertion by 15
      and 30%, respectively. Along the superficial-deep axes the oxidative capacity of
      all fibres increased, the most in fast fibres of the soleus muscle by
      approximately 50%. In soleus muscle, a decrease of cross areas of all fibre types
      from superficial to deep was found, correlating negatively with the succinate
      dehydrogenase activity of the fibres. In extensor digitorum longus muscle the
      change in cross areas of slow-oxidative and fast-oxidative glycolytic fibres was
      dependent on the position of the transversal axis in the muscle. The results
      suggest that distribution patterns of fibre types and the metabolic make up of
      individual muscle fibres are adapted on the basis of local functional demands. In
      both muscles, higher numbers and increased oxidative capacity of fast-glycolytic
      fibres were found during ageing, but variations from superficial to deeper
      regions were irrespective of age.

PMID- 9542581
TI  - Intercellular adhesion molecule-1 (ICAM-1) expression in the liver of patients
      with extrahepatic cholestasis.
AB  - ICAM-1 mediates the recruitment of neutrophils through the endothelium to the
      site of inflammation by the ICAM-1/Mac-1 and ICAM-1/LFA-1 adhesion pathways. In
      extrahepatic cholestasis, recruitment of neutrophils is a main feature of the
      inflammatory infiltrate in areas of parenchymal damage. The aim of the present
      study was to describe the light and electron microscopical localization of ICAM-1
      expression in the liver of cholestatic patients. The peroxidase-antiperoxidase
      technique was used. Increased ICAM-1 expression was detected on sinusoidal
      endothelial and Kupffer cells. A de novo ICAM-1 expression was described on some
      Ito cells and the sinusoidal hepatocyte membrane in areas of parenchymal injury.
      In the portal areas of livers of cholestatic patients, ICAM-1 was observed on the
      endothelial surface of portal veins and on hepatic arteries. Occasionally, ICAM-1
      was found on the surface of bile duct epithelia. It is suggested that ICAM-1
      expression is up-regulated by cytokines like TNF-alpha, IL-1 and interferons
      released from activated Kupffer cells. The mechanisms of ICAM-1 upregulation and
      neutrophil recruitment in the liver during extrahepatic cholestasis are
      discussed.

PMID- 9542582
TI  - Pan-cadherin concentrates apically in uterine epithelial cells during uterine
      closure in the rat.
AB  - The ubiquitous cadherin probe, pan-cadherin was used to study changes in the
      distribution of cadherins in the plasma membrane of rat uterine epithelial cells
      during early pregnancy when the uterine lumen closes down. A major reorganisation
      of cadherin expression was observed to occur in uterine epithelial cells between
      days 1 and 6 of pregnancy with a clear shift in molecular distribution from a
      basal location on day 1 to a distinctly and almost exclusively apical
      distribution by day 6 of pregnancy when the blastocyst is attached. We suggest
      these results indicate participation of this molecule in closure of the uterine
      lumen, a phenomenon well-known to occur in the rat uterus during early pregnancy
      and in which apical surfaces of opposing uterine epithelial cells cohere.

PMID- 9542583
TI  - Distribution of N-cadherin and NCAM in neurons and endocrine cells of the human
      embryonic and fetal gastroenteropancreatic system.
AB  - For the first time, the distribution of N-cadherin and neural cell adhesion
      molecule (NCAM) as well as some neuropeptides in nerve cells and endocrine cells
      of the human embryonic and fetal gastroenteropancreatic system has been detected
      in early stages (from the 6th postovulatory week onwards). Epithelial cells of
      the stomach and small intestine contained gastrin and somatostatin and the
      epithelium of the small intestine also bombesin-positive cells. Myenteric
      ganglionic cells showed both bombesin and VIP and were NCAM- and N-cadherin
      positive at all ages studied. Some basally granulated epithelial cells of
      stomach, duodenum and the upper part of jejunum contained N-cadherin. The number
      of these cells increased from 6th to 10th postovulatory weeks. Nerve cells and
      the cytoplasm of individual epithelial cells of pancreatic ducts were
      immunoreactive for NCAM and N-cadherin. NCAM- and N-cadherin-positive cells also
      appeared in Langerhans islets (> 10 weeks), mainly in their peripheral part. NCAM
      and N-cadherin-positive endocrine cells were less numerous than endocrine cells
      producing somatostatin, bombesin, and VIP, probably reflecting the features of
      embryonic/fetal histogenesis of Langerhans islets from epithelial endocrine cells
      of pancreatic ducts. NCAM and N-cadherin were localized on the surface of
      endocrine islets cells as well as in the cytoplasm of single islet cells. This
      suggests the involvement of both membrane and soluble forms of adhesion proteins
      in embryonic/fetal histogenesis of human pancreatic islets. The early occurrence
      of N-cadherin (6th postovulatory week) in enteroendocrine cells supports the
      existence of a common precursor. The expression of NCAM and N-cadherin in nerve
      cells and endocrine cells of the human fetal gastroenteropancreatic system may
      indicate the involvement of neuronal adhesion mechanisms in the development of
      neuro-endocrine complexes of fetal stomach, small intestine and pancreas.

PMID- 9542584
TI  - Caveolin-3 and nitric oxide synthase I in healthy and diseased skeletal muscle.
AB  - Recently, it has been shown for mouse skeletal muscle that caveolin-3 is
      localized in the sarcolemma and cofractionates with the original dystrophin
      complex (DC). In order to find out whether caveolin-3 is a further component of
      the recently established and enlarged nitric oxide synthase (NOS) I-DC and
      whether members of this complex interact with and are potentially regulated by
      caveolin-3, mammalian and non-mammalian healthy and diseased (dystrophic)
      skeletal muscles were investigated using caveolin-3, NOS I, DC components and
      myosin immunohistochemistry as well as NOS I-associated diaphorase
      histochemistry. In healthy mammalian skeletal muscle, caveolin-3 was colocalized
      with the DC components in all extra- and intrafusal fibers. By contrast, NOS I
      was absent in type I extrafusal fibers of certain species. In patients with
      Duchenne muscular dystrophy and mdx mice the components of the NOS I-DC were not
      detected in all extra- and intrafusal fiber types, while caveolin-3 was found
      unchanged. In healthy non-mammalian skeletal muscle, i.e. of birds, reptiles and
      fishes, caveolin-3 immunoreactivity was lacking in the sarcolemma as was alpha
      sarcoglycan; the other NOS I-DC components were either present or absent. In
      conclusion, although caveolin-3 is localized in the sarcolemma of mammalian
      myofibers, there are differences in the microarchitecture of the components of
      the DC complex and of caveolin-3 which does not appear to be linked with the NOS
      I-DC. Potential regulatory interactions between caveolin-3 and NOS I may
      nevertheless exist in those fibers where both molecules are colocalized. The
      absence of caveolin-3 and alpha-sarcoglycan immunoreactivities in non-mammalian
      myofibers may suggest that the functions of these proteins are subserved by other
      components of NOS I-DC complex.

PMID- 9542585
TI  - Diffuse plaques associated with astroglial amyloid beta protein, possibly showing
      a disappearing stage of senile plaques.
AB  - To clarify whether senile plaques disappear, we examined amyloid beta protein (A
      beta) deposits in non-demented subjects, and found novel diffuse plaques
      associated with astroglial A beta. Formalin-fixed paraffin-embedded sections from
      cortical areas were immunolabeled with a panel of A beta antibodies, and
      astroglial and microglial markers. Cerebral A beta deposition was primarily found
      as diffuse plaques (DP) in these subjects. A subset of DP was associated with
      clusters of intensely A beta-positive small granules. The clusters, which were
      located just adjacent to astroglial nucleus, had the characteristics of
      lipofuscin granules and, therefore, were quite different from "small stellate
      deposits". Substantial amounts of A beta-positive granules were found inside
      astrocytes by dual labeling of A beta and glial fibrillary acid protein, and the
      majority of astroglial A beta immunoreactivity was located on lipofuscin
      granules. A beta-positive granules lacked immunoreactivity with antisera for the
      N-terminal region of A beta. These peculiar DP showed a much weaker staining than
      ordinary DP. The DP associated with astroglial A beta were found in about one
      third of the subjects, although the density varied widely among individuals. From
      these findings, we propose that DP, which are associated with the N-terminal
      truncated A beta in astrocytes, represent the disappearing stage of senile
      plaques.

PMID- 9542586
TI  - Immunolabelling of the cytoplasm and processes of apoptotic facial motoneurons
      following axotomy in the neonatal rat.
AB  - A polyclonal antibody intended to recognize c-Jun (Oncogene Science, c-jun/AP-1,
      Ab-2) has previously been shown to recognize an apparently novel "apoptosis
      specific protein" (ASP) in the cytoplasm of cells undergoing apoptotic cell death
      in vitro. We have investigated whether this antibody would also serve as a
      reliable marker for apoptotic motoneurons in vivo. Following transection of the
      left facial nerve in anesthetized neonatal rat pups, which results in over 90%
      death of the facial motoneurons, we performed immunohistochemistry on frozen
      brain stem sections with Oncogene Science Ab-1 and Ab-2 antibodies which are
      raised against different peptide fragments of c-Jun. While Ab-1/c-Jun labelling
      was seen in the nuclei of the majority of axotomized motoneurons, Ab-2/ASP
      immunoreactivity was present only in scattered cells, all of which had
      characteristic apoptotic morphology. Furthermore, Ab-2/ASP immunoreactivity was
      cytoplasmic and frequently included the dendrites and axons of dying neurons.
      Some cerebellar granule cells undergoing postnatal developmental cell death were
      also Ab-2/ASP positive. The time course of the number of Ab-2/ASP-labelled
      motoneurons corresponded relatively closely with our previous data on DNA
      fragmentation in these cells, as assessed by an in situ end labelling (ISEL)
      technique. When facial nerve axotomy was performed at 7 and 14 days postnatum,
      resulting in reduced cell death, the number of Ab-2/ASP immunoreactive cells
      decreased correspondingly. Although the exact identity of the epitope recognized
      by Ab-2 is unclear, we conclude that, by labelling the cytoplasmic and neuritic
      components of apoptotic motoneurons, Ab-2/ASP immunohistochemistry is a valuable
      complementary technique to existing in situ methods based on the detection of
      fragmented DNA in the cell nucleus.

PMID- 9542587
TI  - Enlarged and phagocytic, but not primed, interleukin-1 alpha-immunoreactive
      microglia increase with age in normal human brain.
AB  - Microglia-mediated inflammatory responses have been implicated in the
      pathogenesis of neuritic plaques in Alzheimer's disease. The strong age
      association of Alzheimer's disease incidence suggests that events in normal aging
      may promote such responses. We used immunohistochemistry and computerized image
      analysis to determine the numbers, size, activation state, and immunoreactive
      intensity of interleukin-1 alpha-immunoreactive (IL-1 alpha +) microglia in
      mesial temporal lobe of 20 neurologically normal individuals, 2-80 years of age.
      We also used Northern analysis to determine tissue levels of IL-1 alpha mRNA in
      an additional 11 neurologically normal individuals aged 1 day to 78 years. IL-1
      alpha + microglia were characterized as primed, enlarged, or phagocytic (enlarged
      with heterogeneous cytoplasmic contents) based on morphology. These three
      microglial subtypes showed significant differences in size [27 +/- 1 58 +/- 2 114
      +/- 6 (mean +/- SEM) micron 2/cell, respectively, P < 0.001 for each comparison]
      and in immunoreactive intensity [60 +/- 1 68 +/- 2 79 +/- 2 (arbitrary units),
      respectively, P < 0.001 or better for each comparison]. There were significant
      age-associated increases in the total numbers of activated IL-1 alpha +
      microglia. Among microglial subtypes, there were significant increases in the
      numbers of enlarged (threefold) and especially phagocytic (elevenfold), but not
      primed, microglia. Tissue IL-1 alpha mRNA levels were higher in individuals over
      60 than in those less than 60 (P < 0.05). The age-associated increases in
      microglial activation were independent of postmortem interval, patient sex, and
      the presence of Alzheimer-type 'senile' changes. Age-associated increases in
      microglial activation and IL-1 expression may contribute to the age-associated
      increased risk of Alzheimer's disease.

PMID- 9542588
TI  - Secondary microvascular degeneration in amyloid angiopathy of patients with
      hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D).
AB  - Various secondary microvascular degenerative and inflammatory alterations may
      complicate cerebral amyloid angiopathy (CAA) and contribute to the morbidity of
      CAA-associated stroke. We have investigated the severity of CAA-associated
      microangiopathy in a genetically determined Dutch form of CAA (HCHWA-D) that has
      major similarities to the type of CAA that more commonly occurs with aging or
      Alzheimer's disease (AD). The presence and extent of the following vascular
      abnormalities was assessed: (1) hyalinization/fibrosis, (2) microaneurysm
      formation, (3) chronic (especially lymphocytic) inflammation, (4) perivascular
      multinucleated giant cells/granulomatous angiitis, (5) macrophages/histiocytes
      within the vessel wall, (6) vessel wall calcification, (7) fibrinoid necrosis,
      and (8) mural or occlusive thrombi. (Of these, calcification of CAA-affected
      vessel walls has, to our knowledge, been described in only a single patient with
      CAA-associated cerebral hemorrhage.) Some of the changes, such as histiocytes in
      blood vessel walls and the relationship of vascular hyalinosis to amyloid beta/A4
      protein deposition, were highlighted by immunohistochemistry. By assessing the
      numbers of sections in which the changes were present for each case, a 'score'
      reflective of CAA-associated angiopathy could be obtained. This 'score' was
      reproducible among several observers. We suggest that it might also be applicable
      to quantifying severe CAA and related microvascular degenerative changes in
      patients with AD. beta/A4 immunoreactivity was often sparse and adventitial (or
      almost absent) in severely hyalinized arterioles and microaneurysms. However,
      macrophages were prominent in the walls of such vessels and may play a role in
      the pathogenesis and progression of CAA-related microvasculopathy.

PMID- 9542590
TI  - Increase in SNAP-25 immunoreactivity in the mossy fibers following transient
      forebrain ischemia in the gerbil.
AB  - SNAP-25 (a synaptosomal-associated protein of 25 kDa) has been shown to be
      involved both in synaptic vesicle exocytosis and in axonal outgrowth. In the
      present study, we investigated the changes in SNAP-25 immunoreactivity in the
      hippocampus of the Mongolian gerbil (Meriones unguiculatus) at different time
      points after transient forebrain ischemia insult. In parallel, immunostaining for
      GAP-43, a protein involved in axonal outgrowth, and for syntaxin-1 (stx1A and
      stx1B), another protein implicated in neurotransmitter release, was also
      analyzed. The animals were subjected to 2.5 or 5 min of transient forebrain
      ischemia through bilateral common carotid occlusion, and examined at different
      intervals after ischemia. SNAP-25 immunoreactivity was increased in the mossy
      fiber layer as early as 2 days after 5 min of ischemia. Increased SNAP-25
      immunoreactivity in mossy fibers was also detected at days 4 and 7 after
      ischemia. On day 15, SNAP-25 staining was similar to that observed in control non
      ischemic animals. In contrast, no changes in GAP-43 and syntaxin-1
      immunoreactivity were observed in the mossy fiber layer following 5 min of
      ischemia. No modifications in SNAP-25, syntaxin-1 or GAP-43 immunoreactivity were
      observed following 2.5 min of ischemia, the longest period for which no neuronal
      damage is observed. These results provide evidence of a specific involvement of
      SNAP-25 in the reactive changes associated with transient forebrain ischemia.

PMID- 9542589
TI  - The fragmented neuronal Golgi apparatus in amyotrophic lateral sclerosis includes
      the trans-Golgi-network: functional implications.
AB  - The Golgi apparatus (GA) of spinal cord motor neurons is fragmented in sporadic
      amyotrophic lateral sclerosis (ALS), and in asymptomatic and symptomatic
      transgenic mice expressing the G93A mutation of the gene of the human Cu,Zn
      superoxide dismutase, found in certain cases of familial ALS (FALS) [Gonatas NK
      (1994) Am J Pathol 145:751-761; Mourelatos Z, et al. (1996) Proc Natl Acad Sci
      USA 93:5472-5477]. A similar fragmentation of the GA has been described in cells
      treated with microtubule-depolymerizing drugs, where the organelle is functional
      and contains both Golgi stacks and trans-Golgi network (TGN), the compartment of
      exit and targeting of proteins processed by the GA. To gain a better definition
      of the structure of the fragmented neuronal GA in ALS, four cases of sporadic ALS
      with numerous Bunina bodies in spinal cord motor neurons were stained with
      antibodies against human TGN and against the lumenal and cytoplasmic domains of
      MG160, a protein of the medial cisternae of the GA. The fragmented GA was stained
      with the three antibodies, indicating the presence of both Golgi stacks and TGN.
      Furthermore, the staining of the fragmented GA by the antiserum against the
      cytoplasmic domain of MG160 indicates that the fragmentation of the GA is not the
      result of a terminal and global cytoplasmic lytic event. The Bunina bodies were
      not stained by the anti-MG160 antibodies, suggesting that they are not derived
      from the GA. The perikarya of neurons with fragmented GA showed normal
      immunoreactivity with antibodies against the heavy neurofilament subunit and
      alpha-tubulin. However, because of the lack of appropriate antibodies the
      localization of proteins such as spectrin, ankyrin, centractin and others which
      link the microtubules with the GA were not done. The findings support the
      hypothesis that, in ALS, the fragmented neuronal GA is functional. Additional
      work with animal models of ALS may establish whether the fragmentation of the GA
      is a sign of early degeneration or a compensatory reaction of the injured motor
      neuron.

PMID- 9542591
TI  - Lectin histochemistry in the aged dog brain.
AB  - Formalin-fixed and paraffin-embedded canine brains were examined histochemically
      using 15 selected lectins. Concanavalin A (Con A), Lens culinaris agglutinin,
      Lycopersicon esculentum agglutinin (LEL) and Limulus polyphemus agglutinin (LPA)
      labeled neurons in an age-dependent manner. These and some other lectins
      [Dolichos biflorus agglutinin (DBA), Vicia villosa agglutinin (VVA), Ricinus
      communis agglutinin 120 (RCA-I), Bandeiraea simplicifolia agglutinin (BSL-I), and
      Phaseolus vulagaris agglutinin-L (PHA-L)] also age-dependently labeled glial
      cells. These results indicate that monosaccharide composition and biochemical
      metabolism in brain cells change with age and that these lectins may be useful as
      histochemical markers for investigating senile changes in the canine brain.
      However, no significant correlation was found between ApopTag-positive and lectin
      positive cells. Amyloid plaques were positive for Con A, DBA, Glycine maximus
      agglutinin (SBA), LEL, PHA-L, Limax flavus agglutinin (LFA) and VVA. Among these
      lectins, VVA, SBA and LFA intensely stained amyloid both in blood vessel walls
      and senile plaque cores. Therefore, the sugar residues recognized by these
      lectins likely play specific roles in beta-amyloid deposition in the aged dog
      brain.

PMID- 9542592
TI  - Regulation of Schwann cell numbers in tellurium-induced neuropathy: apoptosis,
      supernumerary cells and internodal shortening.
AB  - We have used an experimental model of tellurium(Te)-induced demyelinating
      neuropathy in the rat to study cellular mechanisms involved in regulating Schwann
      cell (SC) numbers during remyelination. Starting at postnatal day 21, weaned rats
      were fed a diet containing 1.1% elemental Te. Following 7 days of Te treatment
      and at several time points of post-tellurium treatment (PTe), the animals were
      processed for ultrastructural analysis, SC nuclei quantification and teased fibre
      preparations. It is well-established that Te induces a transient
      demyelinating/remyelinating sequence in sciatic nerves. The loss of the myelin
      sheath in this neuropathy produces active proliferation and overproduction of
      immature SCs. By electron microscopy analysis most mitotic SCs were located along
      demyelinated segments. Quantitative determination of SC nuclei per transverse
      section of sciatic nerve revealed a dramatic increase of SCs at 2 days PTe
      relative to control nerves. The number of SC nuclei then decreased progressively
      during the long-term period of recovery studied (330 days PTe). In Te-treated
      rats, SCs undergoing cell death were regularly found within the nerve fibre
      compartment, especially on demyelinated segments. Dying cells exhibited
      morphological features of apoptosis and appeared enclosed by lamellar processes
      of adjacent healthy SCs in extracellular compartments. Both healthy immature SCs
      and endoneurial macrophages were involved in the phagocytosis of apoptotic SCs.
      Particularly during remyelination, supernumerary endoneurial SCs were observed
      surrounding myelinated fibres. These cells progressively became atrophic with a
      morphological phenotype similar so that of "onion bulb" cells. On the other hand,
      teased fibre measurements revealed a remarkable permanent internodal shortening
      in remyelinated fibres from Te-treated sciatic nerves. These results indicate
      that a portion of redundant immature SCs are susceptible to elimination by
      apoptosis. However, other distinct biological mechanisms such as the persistence
      of supernumerary SCs in the endoneurium and the shortening of internodal lengths
      are also involved in regulating SC numbers during the remyelination stage.

PMID- 9542593
TI  - Enhanced reactivity of Alz-50 antibody in brains of sudden infant death syndrome
      victims versus brains with lethal hypoxic/ischemic injury. Diagnostic
      significance after application of the ImmunoMax technique on routine paraffin
      material.
AB  - Alz-50 antibody is immunoreactive with brain tissue of subjects with Alzheimer's
      disease and can also be demonstrated by immunocytochemistry in neurons of
      vibratome-prepared brain tissue of victims of sudden infant death syndrome
      (SIDS). The application of a slightly modified ImmunoMax method enabled us to
      demonstrate Alz-50 immunoreactivity in paraffin-embedded material. The Alz-50
      epitope was detected in the hippocampus region and in nuclei of the medulla
      oblongata at the level of the inferior olivary protuberance in three diagnostic
      groups: victims of SIDS (n = 10), infants dying of subacute hypoxia/ischemia with
      subsequent (re-)perfusion (n = 9), and infants dying of acute ischemia without
      (re-) perfusion (n = 7). Quantitative evaluation of the hippocampal cortex and
      the nucleus olivaris inferior disclosed a significantly (P < 0.05) higher
      percentage of Alz-50-reactive neurons in SIDS cases than in the control groups
      (hippocampal cortex and the nucleus olivaris; SIDS victims: median = 100%;
      subacute hypoxia/ischemia: median = 33.6-81%; acute ischemia: median = 89.2-99%).
      Semiquantitative analysis revealed an equally pronounced preponderance of Alz-50
      reactive neurons in SIDS victims versus the control groups. This greater
      expression in SIDS victims may be due to an ongoing hypoxia/ischemia during
      agony, but the present paucity of knowledge prohibits definitive elucidation.
      Nevertheless, the method described here appears to offer the realistic
      possibility of distinguishing SIDS cases from cases of sudden death in infants
      due to other causes, i.e., it offers for the first time a positive criterion for
      the diagnosis of SIDS.

PMID- 9542594
TI  - Co-expression of Fas and Fas ligand in malignant glial tumors and cell lines.
AB  - Fas ligand (FasL) is involved in tumor evasion from the immune system. We
      analyzed 22 human gliomas for expression of FasL and its receptor, Fas. Positive
      FasL and Fas immunoreactivity was detected in 13 out of 22 tumors by Western
      blotting and in 15 out of 22 tumors by immunohistochemistry. Immunohistochemistry
      also showed that Fas and FasL expression was confined to tumor cells. Co
      expression of these molecules was confirmed by Western blotting and
      immunohistochemistry in 4 of 7 glioma cell lines. Co-expression of FasL and Fas
      within tumor cells suggests that their contribution in vivo to the process of
      immune system evasion and tumor cell apoptosis is complex and probably involves
      additional factors.

PMID- 9542595
TI  - Rare occurrence of inactivating p53 gene mutations in primary non-astrocytic
      tumors of the central nervous system: reappraisal by yeast functional assay.
AB  - While it is established that p53 mutation plays a critical role in the
      carcinogenesis of astrocytic brain tumors, its role remains to be clarified for
      other types of tumors in the central nervous system (CNS). Using a yeast-based
      assay which tests the ability of human p53 to activate transcription, we analyzed
      p53 mutations in 85 non-astrocytic CNS tumors, including 4 benign neuronal tumors
      (3 central neurocytomas and 1 pineocytoma), 12 primitive neuroectodermal tumors,
      14 germ cell tumors (7 germinomas, 7 non-germinomatous tumors), 4
      craniopharyngiomas, 14 ependymomas, 22 schwannomas, 10 primary brain lymphomas in
      immunocompetent patients, and 5 bone tumors of the skull. The only tumors found
      to contain p53 mutations were 3 malignant lymphomas. The presence of mutations in
      these cases was confirmed by DNA sequencing. Given the high accuracy and
      sensitivity of the yeast assay and previous negative results using conventional
      techniques, this indicates that p53 mutation is a rare event in non-astrocytic
      CNS tumor types examined here.

PMID- 9542596
TI  - Systemic complement depletion reduces inflammation and demyelination in adoptive
      transfer experimental allergic neuritis.
AB  - The effect of systemic complement depletion by cobra venom factor (CVF) was
      evaluated in adoptive transfer experimental allergic neuritis (AT-EAN). Spleen
      cells of rats immunized with a neuritogenic peptide SP26 were injected into naive
      rats. On days 3 and 6 after cell transfer AT-EAN rats were treated with CVF or
      saline intraperitoneally. AT-EAN rats treated with CVF had significantly lower
      scores for histological inflammation (0.25 +/- 0.25 vs 1.9 +/- 0.4, mean +/- SEM,
      P < 0.03) and demyelination (0.13 +/- 0.13 vs 1.6 +/- 1.4, P < 0.02) than saline
      treated AT-EAN rats. Immunocytochemistry of lumbosacral nerve roots showed
      significantly less ED1-positive macrophages (0.5 +/- 0.3 vs 1.6 +/- 0.6, P <
      0.04) and CD11bc-positive (expressing complement receptor 3 or CR3) inflammatory
      cells (0.6 +/- 0.4 vs 1.7 +/- 0.5, P < 0.03). Our data suggest that complement
      plays a crucial role in inflammatory demyelination since systemic complement
      depletion significantly reduces recruitment of macrophages into the nerve and
      subsequent macrophage-mediated demyelination.

PMID- 9542597
TI  - Anti-tubulin antibodies in a sensorimotor neuropathy patient alter tubulin
      polymerization.
AB  - The effect of anti-tubulin antibodies present in the serum of a patient with a
      progressive sensorimotor neuropathy on microtubule assembly was examined. The
      patient's serum was reactive on immunoblots with a single band of proteins of 55
      kDa from homogenates of neural tissues. Tubulin was identified as the
      quantitatively major component of these 55-kDa proteins. Polymerization of
      tubulin in vitro was significantly enhanced by the patient's serum. A monoclonal
      antibody to nerve-specific class III beta-tubulin precisely duplicated the
      immunoreactive profile of the patient's serum, while an antibody to class (I +
      II) beta-tubulins also reacted with tubulins in non-neural tissues. The results
      indicate for the first time that human antisera reactive with nerve specific beta
      tubulin can alter tubulin polymerization-depolymerization dynamics.

PMID- 9542598
TI  - Atypical juvenile neuronal ceroid lipofuscinosis with granular osmiophilic
      deposit-like inclusions in the autonomic nerve cells of the gut wall.
AB  - In this 8-year-old boy, who had been exposed to alcohol and oxazepam during
      pregnancy, visual failure was the first symptom of a neuronal ceroid
      lipofuscinosis (NCL) disorder, noticed at the age of 5 years. Ophthalmological
      examinations revealed a cystic type of macular degeneration, which would be more
      likely to be found in variant late infantile NCL. However, vacuolated lymphocytes
      were found in peripheral blood films and a diagnosis of the juvenile form of NCL
      (JNCL) was made. Molecular genetic studies showed the patient to be homozygous
      for the major mutation of JNCL, a 1.02-kb deletion. In whole-night
      polysomnography, there was significantly more epileptiform activity than in other
      JNCL patients under 10 years of age. Using magnetic resonance imaging, the signal
      intensity of the white matter was increased, especially in the periventricular
      area. In addition, there were enlarged perivascular spaces in the watershead
      areas. The corpus callosum was thin. Finally, in the autonomic ganglion cells of
      the submucosal nerve plexus there were membrane-enclosed homogeneous and granular
      cytosomes resembling the granular osmiophilic deposits of infantile NCL. However,
      extraneural cells, including blood capillaries and smooth muscle, showed
      inclusions with fingerprint and curvilinear profiles. The features of the present
      case indicated a phenotypic variant of JNCL.

PMID- 9542599
TI  - Disseminated perivenous necrotizing encephalomyelitis in systemic lupus
      erythematosus: report of an autopsy case.
AB  - The patient, a 22-year-old woman who had been treated for systemic lupus
      erythematosus (SLE) for 10 years, was hospitalized for arthralgia, melena, and
      difficulty in walking. CT examination of the brain showed grain-like high-density
      lesions scattered throughout the cerebral white matter and basal ganglia. At
      autopsy, multiple perivenous, well-demarcated foci of brownish discoloration were
      seen scattered throughout the cerebral white matter and basal ganglia.
      Histopathologically these lesions consisted of foci of coagulation necrosis
      surrounding the veins. The veins in the foci showed fibrous thickening of the
      walls, but there were no indications of vasculitis. At the periphery of the
      lesions, the axons were better preserved than their myelin sheaths. The
      neuropathological findings in the present case closely resemble those of acute
      disseminated (perivenous) encephalomyelitis, although an inflammatory cell
      infiltration had apparently already subsided. Although its pathogenesis remains
      unclear, this finding should not be regarded as an incidental complication but
      rather as a rare subtype of central nervous system lesion occurring with SLE.

PMID- 9542600
TI  - Neurocytoma/rhabdomyoma (myoneurocytoma) of the cerebellum.
AB  - An unusual case of cerebellar neurocytoma with rhabdomyomatous differentiation in
      a 6-year-old boy is reported. Immunocytochemical and ultrastructural features of
      the tumour were studied. Abortive synapse formation, the presence of clear
      vesicles and synaptophysin immunoreactivity of the tumour cells indicated its
      intermediate neuronal differentiation, while the presence of myoblasts and
      myotubes and immunolabelling by desmin confirmed the rhabdomyomatous
      differentiation. In addition, the mesenchymal cells variably expressed
      neurofilament protein and glial fibrillary acidic protein, suggesting inductive
      interaction between the neuroectodermal and ectomesenchymal elements and
      persistence of the pleuripotential nature of the cells along the rhombic area of
      the brain stem.

PMID- 9542601
TI  - Role of T cells in drug allergies.

PMID- 9542602
TI  - Systemic T-cell unresponsiveness during rush bee-venom immunotherapy.
AB  - By rush bee-venom immunotherapy, subjects reacting allergically to the venom can
      be effectively anergized, although the mechanism of action is not known. Here we
      analyzed the systemic effects of rush desensitization on the T cells of allergic
      patients. In most patients, we found reduced frequencies of T cells recalled to
      express CD69 and the cytokines interleukin (IL)-4 and interferon-gamma (IFN
      gamma) after stimulation of peripheral blood mononuclear cells with phorbol 12
      myristate 13-acetate (PMA) and ionomycin, as compared with normal donors. These
      frequencies are progressively reduced during immunotherapy. The frequency of
      cells expressing IL-2 does not change. A few patients show a different response
      to immunotherapy: frequencies of cells expressing CD69, IL-4, or IFN-gamma do not
      change, and remain similar to those of normal donors. However, the frequency of
      cells able to express IL-2 is increased. The analysis of cytokine expression in
      CD45RO+ vs CD45RO- T-cell populations revealed differences between normal and
      allergic donors. In allergic patients, higher frequencies of IL-4- and IFN-gamma
      expressing cells among the CD45RO- subpopulation were found than in normal
      donors. This situation is not modified by immunotherapy. The results reveal a
      certain degree of heterogeneity in the response of allergic patients to bee-venom
      rush immunotherapy; however, all are clearly differentiated from normal controls
      as judged by cytokine expression of CD45RO- T cells. In most allergic patients, a
      considerable percentage of Th cells become unresponsive to mitogenic stimulation,
      and may be responsible for the desensitization itself.

PMID- 9542603
TI  - Sensitization to Zygophyllum fabago pollen. A clinical and immunologic study.
AB  - Zygophyllum fabago is a herbaceous plant found widely in the Mediterranean area.
      There are no previous reports of its allergenicity. An aerobiologic and clinical
      survey was conducted in Murcia, southern Spain, to determine the quantity of
      airborne pollen and establish the possible role of this pollen as a cause of
      allergic symptoms. With a Hirst volumetric trap, we determined the atmospheric
      concentrations of this pollen in 1993, 1994, 1995, and 1996. Of 1180 patients
      tested, 181 (15.34%) had a positive skin test. To determine its allergenicity, we
      divided 47 patients into three groups: in group 1, all the patients had symptoms
      of rhinoconjunctivitis plus asthma; in groups 2 and 3, rhinoconjunctivitis. In
      group 1, we performed a bronchial provocation test (BPT); in groups 2 and 3, we
      performed nasal provocation (NPT) and conjunctival provocation (CPT) tests,
      respectively. SDS-PAGE was used to characterize the antigenic fractions and RAST
      inhibition to determine cross-reactivity with other pollens. The pollen
      dispersion period is from May to September (445 grains/m3). BPT was positive in
      13 of 15 patients, NPT in 14 of 16 patients, and CPT in 13 of 16 patients. RAST
      inhibition revealed cross-reactivity with Mercurialis, Ricinus, Olea, and Betula.
      SDS-PAGE identified 25 IgE antibody-binding components, five of which (60, 65,
      41, 38, and 15.5/14.7 kDa) were recognized by 40% of the sera. By SDS-PAGE
      immunoblotting with sunflower antiprofilin rabbit serum and affinity
      chromatography we established that the Z. fabago extract has profilin. This study
      shows that this pollen becomes airborne and elicits an IgE response which
      triggers respiratory symptoms in allergic subjects.

PMID- 9542604
TI  - Prevalence of allergy in children in relation to prior BCG vaccination and
      infection with atypical mycobacteria.
AB  - By influence on the Th1/Th2 cell balance, infectious agents may affect the
      development of atopic allergy. In this study, we investigated whether previous
      BCG vaccination or infection with atypical mycobacteria might be related to the
      development of atopic disease. The study, which involved skin testing with
      mycobacteria and answers to a questionnaire for more than 6000 children in
      Sweden, revealed a low prevalence of allergy among BCG-vaccinated children who
      were immigrants or adopted from other countries. Vaccinated children born in
      Sweden, however, did not have significantly lower allergy prevalence than age
      matched, unvaccinated children. Furthermore, the overall frequencies of skin-test
      reactivity to the atypical mycobacteria M. avium and M. scrofulaceum were higher
      rather than lower in allergic than in nonallergic children. By contrast, there
      was a tendency toward a lower frequency of more strongly positive skin reactions
      (> or = 10 mm) to mycobacteria in allergic than in nonallergic children. These
      findings do not support the hypothesis that early mycobacterial infections have a
      suppressive effect on the development of atopic disease. Earlier findings of an
      apparent association between atopy and lack of previous mycobacterial infection
      may possibly be explained by a relatively decreased ability of atopic patients to
      mount strong Th1 cell-mediated immune responses.

PMID- 9542605
TI  - Aeroallergens and viable microbes in sandstorm dust. Potential triggers of
      allergic and nonallergic respiratory ailments.
AB  - Aeroallergens and antigens in sandstorm dust, extracts of which were skin prick
      test (SPT) positive in allergic patients, were detected by rocket
      immunoelectrophoresis and ELISA. Fungi and bacteria isolated by agar settle
      plates and soil dilution and soil washing methods were enumerated and identified.
      Cat dander, Acacia, Alternaria, Aspergillus, Chenopodium, Cladosporium, Bermuda
      grass, Pithecellobium, Prosopis, Rumex, cultivated rye, and Washingtonia palm
      allergens were detected by both methods. Viable microbes including 1892 +/- 325
      colony-forming units (cfu) of bacteria, and 869 +/- 75 cfu of fungi were isolated
      per gram of dust by the soil dilution method. Randomly selected microbial
      colonies on streaking and subculture were found to consist of between two and
      seven mixed colonies. Fungi including Alternaria, Aspergillus, Botrytis,
      Cladosporium, Mortierella, Mucor, Mycelia sterilia, Penicillium, Pythium,
      Ulocladium, Verticillium, and some yeasts were isolated. Actinomyces, Bacillus,
      Pseudomonas, and mostly coagulase-negative Staphylococcus species were
      identified, but the bulk of unidentified bacterial isolates were mainly mixed
      colonies of rods, cocci, coccobacilli, and some filamentous types. Six-hour agar
      settle-plate counts during sandstorms were 100 and 40% higher for bacteria and
      fungi, respectively, than without sandstorms. The most abundant aeroallergens
      were those of Acacia, Alternaria, Aspergillus, Bermuda grass, Cladosporium,
      cultivated rye, Prosopis, and cat dander. Pithecellobium dulce, Rumex crispus,
      and Washingtonia palm allergens were detectable for the first time in Riyadh. IgE
      reactivities of the dust in man were demonstrated by ELISA using sera from
      atopic, exposed, and normal subjects. These results indicate that sandstorm dust
      is a prolific source of potential triggers of allergic and nonallergic
      respiratory ailments, and the methods mentioned here should be routinely used for
      quick sampling of the environment.

PMID- 9542606
TI  - Airborne grass (Poaceae) pollen in southern Spain. Results of a 10-year study
      (1987-96).
AB  - This work reports an exhaustive study of the aerobiology of the Gramineae in
      Seville, Spain, which is typical of coastal Mediterranean areas. Sampling was
      done with a Cour trap installed on the roof terrace of the School of Pharmacy,
      Seville, from 1987 to 1996, both inclusive. The climatic pattern of that period
      was characterized by two exceptionally wet years (1989 and 1996), between which
      were 5 consecutive years of drought (1990-5). This typically Mediterranean
      climate affects grass aerobiology. The annual amounts of total grass pollen are
      low, never exceeding 2500 grains/m3. The start, length, and intensity of the
      pollen season are significantly correlated with preseasonal meteorologic factors
      (precipitation and temperature), but intraseasonal meteorologic conditions have
      no effect on the three variables. The relationships are stated by three equations
      that, while further years of observations are anticipated, can be considered
      models to forecast the characteristics of the pollen season: the starting date
      depends on the mean temperatures of January and February, and the length and
      intensity of the season depend on the rainfall between the beginning of January
      and the starting date of the season. For the study period, the weekly
      concentrations (pollen curves) throughout the year showed no typical pattern of
      variation over the years, so that it was impossible to make mid- and long-term
      forecasts of the variation in weekly concentration. The most noteworthy aspects
      of grass pollen curves are a long pollen season, which starts in February or
      March and lasts until September or October; peaks of higher concentration (> 100
      grains/m3) in May and June, associated with increases in temperature and absence
      of precipitation; and other peaks in the summer months that may be as high as the
      spring peaks.

PMID- 9542607
TI  - Allergen-specific increase in interleukin (IL)-4 and IL-5 secretion from
      peripheral blood mononuclear cells during birch-pollen immunotherapy.
AB  - The mechanisms behind the effects of immunotherapy (IT) with birch-pollen extract
      are largely unknown. In this pilot study, we measured the cytokine secretion in
      vitro from peripheral blood mononuclear cells (PBMC) obtained from birch-pollen
      allergic patients undergoing IT treatment (n = 4) or placebo administration (n =
      4), collected before treatment, 1 and 4 weeks after start of treatment, and
      during and just after the pollen season (12-14 weeks after start of treatment).
      The PBMC were stimulated with birch-pollen extract in vitro for 7 days, followed
      by restimulation with the mitogens phytohemagglutinin (PHA) and phorbol 12
      myristate 13-acetate (PMA) for 24 h, to enhance the production of cytokines. The
      supernatants were analyzed with ELISA and radioimmunoassay for interferon-gamma
      (IFN-gamma), interleukin (IL)-4, and IL-5. In the therapy group, we noted an
      increased secretion of IL-4 and IL-5 from PBMC collected at 4 weeks after the
      start of treatment (IL-4: 29 +/- 21 pg/ml [day 0] to 374 +/- 448 pg/ml [week 4],
      mean +/- SD; IL-5: 95 +/- 48 pg/ml to 1147 +/- 697 pg/ml). No increase was seen
      in the placebo group. During the pollen season, we noted a trend toward increased
      IL-4 and IL-5 secretion in both groups. We conclude that the temporary increase
      in serum IgE observed in many IT studies may be a consequence of increased IL-4
      production due to the allergen exposure.

PMID- 9542608
TI  - Late skin-prick-test reactions to malted wheat. Clinical observations and
      immunohistochemical characterization.
AB  - This study reports late skin-prick-test (SPT) reactions in seven bakers and seven
      control subjects to malted wheat appearing after 6-10 h, and not preceded by an
      immediate-phase reaction. Two subjects in each group had a history of atopic
      symptoms and were Phadiatope positive. Serologic IgE analysis (RAST) of normal
      wheat flour and of malted wheat grain was negative in all subjects. Skin biopsy
      specimens were obtained 16-18 h after SPT to malted wheat grain and to histamine
      and from untested skin. The late SPT reactions in all participants had an
      urticarial appearance, clinically and in routine histology. Immunohistologically
      mild to moderate perivascular dermal cell infiltrates were observed in both
      groups, consisting mainly of CD4+ and HLA-DR+ cells. The number of CD1a+
      epidermal cells was statistically significantly higher (P < 0.01) in the bakers'
      prick-tested skin compared to that of the controls, a fact which might reflect
      preparedness to react upon challenge. There were no statistical differences
      between the two groups in IgE+ epidermal cells or epidermal cells expressing the
      high-affinity IgE receptor (Fc epsilon RI). However, there was a correlation
      between serum-IgE levels and the number of IgE+ epidermal cells. The late skin
      reactions observed in both bakers and controls were probably more of an irritant
      or toxic than immune-mediated nature, but they raise the question of whether skin
      contact with malted flour contributes to an unfavorable prognosis of hand eczema
      in bakers.

PMID- 9542609
TI  - Determination and characterization of cross-reacting allergens in latex, avocado,
      banana, and kiwi fruit.
AB  - Sera of 11 patients were used to characterize allergens in kiwi fruit, latex,
      avocado, and banana by SDS-PAGE/immunoblotting and to determine cross-reactions
      between these allergen extracts in EAST inhibition and immunoblot inhibition. By
      SDS-PAGE/immunoblotting, allergens with apparent molecular weights of 21, 38, 40,
      and 42 kDa were visualized in latex extract. In avocado extract, IgE-binding
      components of 27, 43, 52, 58, 65, 75, and 88 kDa were to be seen, whereas, in
      banana extract, a 40-kDa protein showed strong IgE binding. Furthermore,
      allergens of 52, 58, 88, and 94 kDa were detected in the extract of banana. Cross
      reactions between these allergen extracts were determined by EAST inhibition.
      Immunoblot inhibition demonstrated that almost all IgE-reactive bands in
      nitrocellulose-blotted latex, avocado, and banana extracts and two components of
      43 and 67 kDa in kiwi fruit shared common IgE epitopes.

PMID- 9542610
TI  - Comparison of olfactory function in patients with seasonal and perennial allergic
      rhinitis.
AB  - Hyposmia is a common symptom in allergic rhinitis. However, little is known about
      differences in the olfactory function of patients with seasonal or perennial
      allergy. A prospective controlled study was performed on 28 patients with
      allergic rhinitis to grass pollen and on 47 patients with allergic rhinitis to
      mites. Sixty-six healthy volunteers served as a control. Olfactory function was
      evaluated by a modified Connecticut Chemosensory Clinical Research Center testing
      procedure for threshold, identification, and discrimination. The grass pollen
      allergic patients were tested preseasonally and after 3 weeks of intraseasonal
      grass pollen exposure; the mite-allergic patients and the volunteers were tested
      once. In the mite allergics, olfactory threshold, identification, and
      discrimination tests were significantly worse than in the volunteers (all P <
      0.0001). In the grass pollen allergics, the results in olfactory identification
      and discrimination tests were not different from the controls if tested out of
      the season (both P > 0.05). However, in threshold testing (P = 0.0139), the
      results were worse. Intraseasonally, the grass pollen allergics showed a
      significant decrease in threshold, identification (both P < 0.0001), and
      discrimination testing (P = 0.0029). If the intraseasonal pollen allergics were
      compared to the mite allergics, they showed better results in identification (P =
      0.0087) and threshold (P < 0.0001) tests, but worse results in discrimination
      testing (P = 0.0002). Therefore, the different kind of allergen exposure seems to
      result in a different pattern of allergic olfactory dysfunction.

PMID- 9542611
TI  - Factors determining spontaneous histamine release from human basophils purified
      with Percoll gradients and Dynabeads.
AB  - Identification of factors influencing histamine release from purified and
      cultured basophil leukocytes is important for proper interpretation of results
      obtained on histamine release. This paper describes factors that influence
      spontaneous histamine secretion from human basophil leukocytes purified on
      Percoll gradients, followed by negative selection with Dynabeads. Anti-IgE and
      recombinant human interleukin-3 were used as model stimulants, and the purified
      basophil leukocytes were stimulated for 10 min and 6 h. The effect of the
      following conditions was examined: Percoll temperature, cell-suspension density,
      and serum in the media. The results showed that low Percoll temperature, high
      cell-suspension density, and the presence of serum in the media decreased
      spontaneous histamine release and increased maximal net histamine release upon
      stimulation.

PMID- 9542612
TI  - Milk hypersensitivity--key to poorly defined gastrointestinal symptoms in adults.
AB  - Lactose intolerance is a common adverse reaction to milk in adults, while milk
      hypersensitivity is a disorder of infancy. We hypothesized that milk
      hypersensitivity may cause many unspecific gastrointestinal disorders in adults.
      Twenty adults were subjected to double-blind, placebo-controlled milk challenge.
      Phagocyte activity, and Fc gamma and complement receptor expression of phagocytes
      were assayed, and serum total IgE, milk-specific IgE, and serum reactivity to
      milk protein were determined. The challenge increased phagocyte activity and
      complement receptor expression of phagocytes in subjects designated milk
      hypersensitive, who had gastrointestinal symptoms from milk ingestion but normal
      lactose tolerance. The increase was not detected in lactose-intolerant or control
      subjects. The milk-hypersensitive group was also distinguished from the lactose
      intolerant group by enhanced serum reactivity to milk protein. Only two out of
      nine milk-hypersensitive subjects had detectable milk-specific serum IgE. It is
      concluded that milk hypersensitivity in adults, occurring as gastrointestinal
      reactions, may be more common than previously thought.

PMID- 9542613
TI  - Isolation and immunobiochemical characterization of a major allergen (65 kDa)
      from Fusarium equiseti.
AB  - Fusarium equiseti is one of the most important species in the class
      Deuteromycetes (Fungi Imperfecti). For proper diagnosis and immunotherapy,
      isolation and characterization of allergens of F. equiseti are necessary. In the
      present study, culture filtrate (CF) extract of F. equiseti was resolved into 35
      37 bands on isoelectric focusing pI (3-9) and SDS-PAGE (mol. wt. 10-100 kDa).
      Most of them were glycoproteins, as identified by PAS staining. F. equiseti CF
      revealed 15 allergenic proteins on immunoblot with an allergic serum pool. It was
      fractionated into nine fractions (I-IX) on a Superose-12 column by FPLC. Fraction
      IV (65 kDa) and fraction VI (25 kDa) were found to be highly allergenic by IgE
      ELISA. A 65-kDa protein was observed as a major allergen because it was
      recognized by most of the patient sera on immunoblot. After elution from SDS-PAGE
      gel, it gave two bands of pI 7.4 and 6.0. Inhibition in IgE-binding components of
      F. equiseti CF with CF extracts of F. solani and F. moniliforme by immunoprint
      inhibition assay indicated the allergenicity shared between the extracts of
      Fusarium species. Data suggested that the 65-kDa is the major allergen in the
      Fusarium species and can be used for the treatment of allergic patients.

PMID- 9542614
TI  - Comparison of the oral health status and salivary flow rate of asthmatic patients
      with those of nonasthmatic adults--results of a pilot study.
AB  - The oral health status and stimulated salivary flow rate of 33 adult asthmatic
      outpatients were compared with those of 33 nonasthmatic controls. The groups were
      matched by age and sex, and an adjustment for education was made in the
      statistical analysis. In the oral examination, a small difference in the
      prevalence of caries was observed when the sums of decayed, missing, and filled
      teeth (DMFT) were compared. The mean (SD) crude DMFT score was 20.1 (5.8) in the
      asthma group and 18.4 (7.6) in the control group. A statistically significant
      difference was seen in the amount of periodontal inflammation and in the
      stimulated salivary flow rate between the groups. The mean (SD) crude periodontal
      status index (PSI) was 52.7% (23.8%) in the asthmatics and 37.1% (20.4%) in the
      controls. The 95% confidence interval (95% CI) for the difference in adjusted
      means of PSI ranged from 0.1% to 21.9% (P = 0.05). In the stimulated salivary
      flow rate, crude mean values were 1.0 (0.5) ml/min and 1.3 (0.5) ml/min,
      respectively, and the 95% CI for the difference was from 0.05 ml/min to 0.57
      ml/min (P = 0.01). Mucosal lesions in the oral cavity were found in 15 asthmatics
      (45%) and in eight controls (24%). In conclusion, the results of this study
      support the hypothesis that adult asthmatics have a higher risk of oral diseases
      than nonasthmatic subjects.

PMID- 9542615
TI  - A case of episodic angioedema associated with blood eosinophilia: upregulated C5a
      receptor expression on eosinophils.
AB  - A 47-year-old woman was admitted to hospital complaining of swelling and pain of
      the extremities, accompanied by high fever and generalized erythema. Laboratory
      examination showed marked blood eosinophilia with elevation of IgM, IgE, and C
      reactive protein. All autoantibodies examined were negative. The heart and lungs
      showed no untoward findings. Biopsies of the skin and muscle revealed cellular
      infiltration of eosinophils around small blood vessels. Quantitation of C5a
      receptor (C5aR) expression by flow cytometry using anti-C5aR antibody showed
      upregulated expression of C5aR on blood eosinophils but downregulated expression
      on neutrophils. The abnormal C5aR expression on eosinophils and neutrophils
      became normal after spontaneous resolution of symptoms and blood eosinophilia.
      The possibility that C5aR expression on granulocytes is related to the
      pathogenesis of this syndrome may be considered.

PMID- 9542616
TI  - Allergy to adhesive plaster.

PMID- 9542617
TI  - Non-IgE-mediated anaphylaxis to sesame.

PMID- 9542618
TI  - Evaluation of nasal cytology: a comparison between methods.

PMID- 9542619
TI  - Occupational asthma to hyacinth.

PMID- 9542620
TI  - Anaphylaxis after prednisone.

PMID- 9542621
TI  - Syndromes associated with eosinopenia.

PMID- 9542622
TI  - Conjunctivitis to thimerosal mistaken as hay fever.

PMID- 9542623
TI  - Cell cross-contamination in cell cultures: the silent and neglected danger.
AB  - Cell cross-contamination in cell cultures is a common problem during cell
      culturing and use. Contamination invalidates research results, compromises the
      comparison of results between laboratories, reduces reproducibility required in
      industrial production of cell lines, and may lead to unusable therapeutic
      products. The problem can be solved by increasing the awareness of its
      seriousness and by introducing regular quality control of cell cross
      contamination in every laboratory where cells are grown and used.

PMID- 9542624
TI  - Preparation of a pressurization system to study the effect of hydrostatic
      pressure on chondrocyte cultures.

PMID- 9542625
TI  - Aneuploidy induced by cyclophosphamide in developing rat testes.

PMID- 9542626
TI  - Construction of Xenopus (B3.2) and human (HeLa) cell lines expressing the
      tetracycline-controlled transactivator (tTA)

PMID- 9542627
TI  - Cultured human nasal gland cells in a three-dimensional collagen gel.

PMID- 9542628
TI  - Ca2+ mobilization in fetal-human cardiac myocytes is stimulated by isoproterenol
      and inhibited by ryanodine.

PMID- 9542629
TI  - Promoting matrix invasion by human lung epithelial cells.

PMID- 9542630
TI  - Integrins: utility as cell type- and stage-specific markers for hepatocellular
      carcinoma and cholangiocarcinoma.

PMID- 9542631
TI  - A simple method for freezing and storing viable tissue fragments.

PMID- 9542632
TI  - The effect of impermeable oxidants on the growth of neoplastic cells.

PMID- 9542633
TI  - Sensitivity of isoenzyme analysis for the detection of interspecies cell line
      cross-contamination.
AB  - The analysis of the gel electrophoresis banding patterns and relative migration
      distances for the individual isoforms of intracellular enzymes, such as lactate
      dehydrogenase, purine nucleoside phosphorylase, glucose-6-phosphate
      dehydrogenase, and malate dehydrogenase, is used routinely in the
      biopharmaceutical industry for confirmation of cell line species of origin. In
      the present study, the sensitivity of the technique (AuthentiKit, Innovative
      Chemistry, Marshfield, MA) for determining interspecies cell line cross
      contamination was examined. Extracts were prepared from a CHO-K1 line (AA8,
      Chinese hamster), MRC-5 (human) cells, and L929 (mouse) cells and from several
      proportional mixtures of the various binary combinations of cells. The isoenzymes
      were analyzed according to standard procedures for the technique. Contamination
      of MRC-5 cells with CHO-K1 or with L929 cells was clearly detectable with each
      enzyme analyzed. Similarly, the contamination of L929 or CHO-K1 cells with MRC-5
      cells was readily apparent with each enzyme. On the other hand, contamination of
      CHO-K1 cells with L929 cells was only detected with lactate dehydrogenase
      analysis, and contamination of L929 cells with CHO-K1 cells was not detected with
      any of the four enzymes examined. For the latter case, the analysis of an
      additional enzyme (peptidase B) was required. The results indicate that
      interspecies cross-contamination should be detectable with isoenzyme analysis if
      the contaminating cells represent at least 10% of the total cell population.

PMID- 9542634
TI  - Primary culture of choroidal epithelial cells: characterization of an in vitro
      model of blood-CSF barrier.
AB  - A primary rat choroidal epithelial cell culture system was developed to
      investigate mechanisms of heavy metal toxicity on the blood-cerebrospinal fluid
      (CSF) barrier. Epithelial cells were dissociated from choroidal tissue by pronase
      digestion and cultured in standard DMEM culture media supplemented with 10% fetal
      bovine serum and 10 ng epithelial growth factor per ml. The procedure yielded 2-5
      x 10(4) cells from pooled plexuses of three to four rats, and a viability of 77
      85%. The cultures displayed a dominant polygonal type of epithelial cells, with a
      population doubling time of 2-3 d. The cultures were of distinct choroidal
      epithelial origins. For example, immunocytochemical studies using monospecific
      rabbit anti-rat TTR polyclonal antibody revealed a strong positive stain of
      transthyretin (TTR), a thyroxine transport protein exclusively produced by the
      choroidal epithelia. Also, reverse-transcriptase polymerase chain reaction (PCR)
      confirmed the presence of specific TTR mRNA in the cultures. The cultures were
      further adapted to grow on a freely permeable membrane sandwiched between two
      culture chambers. The formation of an impermeable confluent monolayer occurred
      within 5 d after seeding and was verified by the presence of a steady electrical
      resistance across the membrane (80 +/- 10 ohm per cm2). The epithelial barriers
      appeared to actively transport [125I]-thyroxine from the basal to apical chamber.
      These results suggest that this primary cell culture system possesses typical
      choroidal epithelial characteristics and appears to be a suitable model for in
      vitro mechanistic investigations of blood-CSF barrier.

PMID- 9542635
TI  - Reconstituted human oral and esophageal mucosa in culture.
AB  - We have successfully established monolayer and organotypic culture techniques for
      growing human oral and esophageal epithelial cells. Cells in monolayer culture
      were grown in serum-free medium, modified from techniques previously reported by
      our group. The organotypic cultures were grown in a defined medium supplemented
      with 10% fetal calf serum. Oral and esophageal cells were maintained in
      keratinocyte basal medium with pituitary extract and other supplements, and 0.05
      mM calcium for 7-9 and 9-11 passages, respectively. Both cell types had similar
      morphology by phase contrast microscopy. When confluent, the cells were
      predominantly small, basaloid, and uniform and interspersed with larger,
      differentiated cells. By immunohistochemistry, both cell types in monolayer were
      positive to AE1, AE3, and 34BE12 antibodies to keratins of stratified epithelia.
      Oral epithelial cells in monolayer also were positive to 35BH11, representative
      of simple epithelial keratins, while esophageal cells were not. The esophageal
      cells were focally positive to K13, while the oral cells were negative. Both were
      negative for K19. When comparing monolayer to organotypic cultures and to in vivo
      specimens, there was a significant difference in the expression of keratins.
      Using organotypic cultures, AE1, AE3, and 34BE12 were strongly positive in both
      oral and esophageal cells, similar to in vivo tissues. In contrast to monolayers,
      both were also focally positive for K19. Esophageal cells were strongly positive
      for K13, while the oral cells were mildly but uniformly positive. Both were
      negative for keratins of simple epithelia. These two cell culture techniques
      offer unique opportunities to study the pathobiology, including carcinogenesis,
      of stable cell systems from the oral and esophageal epithelia.

PMID- 9542636
TI  - Establishment and characterization of a porcine kidney cell line, FS-L3, which
      forms unique multicellular domes in serum-free culture.
AB  - A stable porcine kidney epithelial cell line, FS-L3, was established and
      maintained in Eagle's minimum essential medium containing 0.295% tryptose
      phosphate broth, 0.5% Bacto Peptone, and 10 mM N, N-Bis (2-hydroxyethyl)-2
      aminoethanesulfonic acid without any serum. The mode of chromosomes is 37 to 38.
      The FS-L3 cells formed fluid-filled, multicellular, three-dimensional domes on a
      single monolayer. The number of domes increased markedly after further
      cultivation. The origin of this cell line was confirmed as porcine by
      hybridization using PRE-1, which can be detected as a specific sequence in the
      porcine genome. It was also found that FS-L3 cells were free from possible
      adventitious viruses and mycoplasmas.

PMID- 9542637
TI  - Development and characterization of SV40 immortalized rat parotid acinar cell
      lines.
AB  - Rat parotid salivary gland acinar cells were transfected by CaPO4 precipitation
      using a plasmid containing a replication-defective simian virus (SV40) genome.
      Out of 30 clonal cell lines, 2 were shown to have moderate to high levels of
      cytodifferentiation and salivary gland acinar cell function. Functional studies
      with the two cell lines indicated that the beta-adrenergic agonist
      (isoproterenol), vasoactive intestinal peptide prostaglandin E1, and forskolin
      were effective activators of intracellular cyclic adenosine 3':5'-cyclic
      monophosphate production. Phenylephrine, carbamylcholine, and UTP were effective
      in increasing inositol phosphate production and intracellular free calcium
      levels, whereas substance P was without affect. Utilizing indirect
      immunofluorescence analysis, both cell lines were shown to express the SV40 large
      T antigen. Electron microscopic evaluation documented moderate to high levels of
      cytodifferentiation with the maintenance of tripartite junctional complexes,
      cellular polarization, and presence of moderate amounts of secretory granules and
      rough endoplasmic reticulum. The two cell lines had doubling times of 22 and 36
      h, respectively.

PMID- 9542638
TI  - Stimulation of rat hepatocyte proliferation in vitro and in vivo by factors
      derived from the bovine small intestinal mucosa.
AB  - A factor with a molecular weight of less than 1 kDa in the mucosa of the bovine
      small intestine (low molecular weight factor or LMW factor) stimulated DNA
      synthesis in rat hepatocytes in primary culture. This factor only showed its
      activity when it was added with a larger factor with a molecular weight of 30 kDa
      that was also found in the same tissue (high molecular weight factor or HMW
      factor). The LMW factor probably acts to enhance the action of a hepatotrophic
      growth factor, since EGF and HGF can substitute for the HMW factor. The action of
      the LMW factor was not due to the actions of low molecular weight substances such
      as norepinephrine, estradiol, triiodothyronine, and putrescine, which enhance the
      action of EGF or HGF, since substantial amounts of these substances were not
      found in the extract. When intraperitoneally administered into rats, after two
      thirds hepatectomy, the LMW factor enhanced hepatocyte proliferation without the
      administration of the HMW factor. In the regenerating liver, a hepatotrophic
      growth factor(s), which acts synergistically with the LMW factor, might be
      properly provided, but the supply of the LMW factor might be below the level that
      maximally stimulates hepatocyte proliferation.

PMID- 9542639
TI  - Cross-talk between signaling pathways in murine embryonic palate cells: effect of
      TGF beta and cAMP on EGF-induced DNA synthesis.
AB  - Signaling pathways utilized by EGF, cAMP, and TGF beta have been demonstrated to
      play critical roles in normal palate development. Stimulation of these pathways
      has been shown in palate cells and numerous other systems to affect cell growth.
      Because proper regulation of cell growth is critical to palate development, we
      speculate that fine regulation of palatal cell growth may be accomplished through
      crosstalk between these signaling pathways. We therefore set out to determine the
      effects of cAMP and TGF beta on EGF-induced cell proliferation in murine
      embryonic palate cells. We found that both TGF beta and cAMP inhibited the
      proliferative response of cells to treatment with EGF, whereas H89, a serine/
      threonine protein kinase inhibitor with selectivity towards cAMP-dependent
      protein kinase, increased the cells' proliferative response to EGF. Genestein, a
      selective inhibitor of tyrosine kinases, at high doses abrogated the cells'
      proliferative response to EGF, confirming that EGF's ability to induce cell
      proliferation is critically dependent upon tyrosine kinase activity. Lower doses
      of genestein, however, actually enhanced cellular response to EGF. The data
      suggest that both the TGF beta- and cAMP-mediated signaling pathways may be
      involved in modulation of the effects of EGF on palate cell growth in vivo.

PMID- 9542640
TI  - In vitro and in vivo host range of Anticarsia gemmatalis multiple nuclear
      polyhedrosis virus.
AB  - A clone of the wild type (wt) Anticarsia gemmatalis multiple nuclear polyhedrosis
      virus AgMNPV, derived from a geographical isolate (Hondrina, Brazil) and
      designated AgMNPV-CL4-3A1, was used to determine the host range of this virus in
      six established lepidopteran cell lines: Anticarsia gemmatalis (BCIRL-AG-AM1),
      Helicoverpa zea (BCIRL-HZ-AM1), Heliothis virescens (BCIRL-HV-AM1), Helicoverpa
      armigera (BCIRL-HA-AM1), Trichoplusia ni (TN-CL1), Bombyx mori (BMN), and a
      coleopteran cell line Anthonomus grandis (BRL-AG-1). In addition, the in vivo
      host range of this clone was also assayed in larvae of Helicoverpa zea, Heliothis
      virescens, Trichoplusia ni, and the homologous species Anticarsia gemmatalis by
      probit analysis. On the basis of temporal studies of TCID50 values, BCIRL-HV-AM1
      cells gave the highest extracellular virus (ECV) titer (9.7 x 10(6) TCID50/ml)
      followed by BCIRL-HA-AM1 cells (8.3 x 10(5) TCID50/ml) and BCIRL-AG-AM1 cells
      (3.2 x 10(5) TCID50/ml). In addition, a low ECV titer of 1.37 x 10(3) TCID50/ml
      was detected from TN-CL1 cells 96 h postinoculation, while BRL-AG-1, BMN, and
      BCIRL-HZ-AM1 cells were nonpermissive to AgMNPV-CL4-3A1 on the basis of TCID50
      results. AgMNPV-CL4-3A1 and the wild type AgMNPV had similar restriction profiles
      that were different from wild type AcMNPV. The LC50 values were 96.9, 564.6,
      733.3, and 1.1 x 10(4) occlusion bodies/cm2 of diet for A. gemmatalis,
      Helicoverpa zea, Heliothis virescens, and T. ni, respectively.

PMID- 9542641
TI  - A novel synoviocyte line (RAMAK-1), derived from a patient with rheumatoid
      arthritis.

PMID- 9542642
TI  - M-CMRL, a new axenic medium to replace indicator cell cultures for the isolation
      of all strains of Mycoplasma hyorhinis.

PMID- 9542643
TI  - Cell-material systems for anterior cruciate ligament regeneration.

PMID- 9542644
TI  - Establishment of a human leukemia HL-60 cell line that expresses high levels of M
      CSF receptors.

PMID- 9542645
TI  - B-lymphoblastoid cell lines from cancer patients.

PMID- 9542646
TI  - N-glycosylation of a baculovirus-expressed recombinant glycoprotein in three
      insect cell lines.
AB  - The capacity of two Trichoplusia ni (TN-368 and BTI-Tn-5b 1-4) and a Spodoptera
      frugiperda (IPLB-SF-21A) cell lines to glycosylate recombinant, baculovirus
      encoded, secreted, placental alkaline phosphatase was compared. The alkaline
      phosphatase from serum-containing, cell culture medium was purified by phosphate
      affinity column chromatography. The N-linked oligosaccharides were released from
      the purified protein with PNGase F and analyzed by fluorophore-assisted
      carbohydrate electrophoresis. The majority of oligosaccharide structures produced
      by the three cell lines contained two or three mannose residues, with and without
      core fucosylation, but there were structures containing up to seven mannose
      residues. The oligosaccharides that were qualitatively or quantitatively
      different between the cell lines were sequenced with glycosidase digestions. The
      S. frugiperda cells produced more fucosylated oligosaccharides than either of the
      T. ni cell lines. The smallest oligosaccharide produced by S. frugiperda cells
      was branched trimannose. In contrast, both T. ni cell lines produced
      predominantly dimannose and linear trimannose structures devoid of alpha 1-3
      linked mannose.

PMID- 9542647
TI  - Massive culture of human liver cancer cells in a newly developed radial flow
      bioreactor system: ultrafine structure of functionally enhanced hepatocarcinoma
      cell lines.
AB  - With a view to initiating clinical trials, cell morphology and function for a
      newly developed artificial liver support system employing highly functional human
      liver cell line, FLC-7, cultured in a radial flow bioreactor were compared to
      cells grown in a conventional monolayer culture. The radial flow bioreactor
      consists of a vertically extended cylindrical matrix comprised of porous glass
      bead microcarriers through which liquid medium flows from the periphery in toward
      the central axis generating a beneficial concentration gradient of oxygen and
      nutrients, while preventing excessive shear stresses or buildup of waste
      products. The three-dimensional culture system supports high-density (1.1 x 10(8)
      cells/ml-matrix), large scale cultures (4.4 x 10(10) cells/400 ml-bioreactor)
      with long-term viability. Scanning and transmission electron microscopy (SEM and
      TEM) revealed that cells cultured in a monolayer system were flattened and
      extended with numerous cytoplasmic projections. Cells in the three-dimensional
      culture were spherical and covered with microvillilike processes resembling liver
      cells in vivo. The cells were solidly attached on the surfaces and within the
      pores of the microcarriers in highly dense colonies. The spherical cells remained
      in close contact with adjacent cells, while circulation of liquid medium flowed
      freely through spaces between cells. FLC-7 cells produced albumin at a rate of
      6.41 micrograms/24 h/10(6) cells. Alpha-fetoprotein (AFP) production dropped
      nearly threefold in comparison to monolayer cultures. Results demonstrated that
      the new artificial liver support systems (ALSS) provides a superior three
      dimensional culture environment that allows cells to perform at naturally
      functioning levels.

PMID- 9542648
TI  - Ecdysteroid resistant subclones of the epithelial cell line from Chironomus
      tentans (Insecta, Diptera). I. Selection and characterization of resistant
      clones.
AB  - Chironomus tentans cells were cultured in the presence of gradually increasing
      concentrations of 20-OH-ecdysone or a nonsteroidal molting hormone agonist, the
      benzoylhydrazine RH 5992, for a period of about 2 yr. From these cultures,
      subclones were selected, which are resistant to up to 25 microM 20-OH-ecdysone
      according to morphological (changes in cell shape and cell arrangement) and
      physiological criteria (acetylcholinesterase induction, secretion of chitinolytic
      enzymes, thymidine incorporation). Some subclones, selected in the presence of 20
      OH-ecdysone, are resistant only to molting hormone, but still respond to RH 5992
      morphologically and biochemically, whereas subclones selected in the presence of
      the benzoylhydrazine showed no reaction neither to 20-OH-ecdysone nor to the
      hormone agonist. Hormone resistance is stable; 3 mo. after hormone withdrawal,
      resistant clones still do not respond to renewed exposure to 20-OH-ecdysone or RH
      5992, respectively. Because in all resistant subclones tested so far all
      hormonally regulated responses known from sensitive cells were no longer
      detectable, it is assumed that the hormone signaling pathway itself is
      interrupted. Possible mechanisms of hormone resistance were discussed.

PMID- 9542649
TI  - Culture of chondrocytes in alginate gel: variations in conditions of gelation
      influence the structure of the alginate gel, and the arrangement and morphology
      of proliferating chondrocytes.
AB  - Sodium alginate, which gels in the presence of calcium ions, is commonly used for
      culture of anchorage-independent cells, such as chondrocytes. Normally, the gel
      appears microscopically homogeneous but, depending on the conditions of gelation,
      it may contain a varying number of small channels that extend inward from the
      surface. We have examined the influence of these channels on the morphology of
      cultured chondrocytes entrapped in alginate beads. Growth-plate or articular
      chondrocytes cultured in alginate normally proliferate and form rounded cell
      clusters but, in alginate beads containing numerous channels, many chondrocytes
      become aligned and form columns similar to those in the growth plate in vivo. As
      the pattern of cellular growth and morphology in alginate is profoundly
      influenced by the presence of channels in the gel, further studies were conducted
      to determine what specific conditions of gelation affect their formation. The
      channels are especially numerous when both the alginate and the gelling solutions
      lack sodium ions or other monovalent cations. The channels are cavities in the
      gel formed by particulate blocking of the rapid diffusion of calcium ions from
      the gelling solution into the boundary of the calcium alginate solution, and
      hence they extend inward from cells at the surface of the alginate gel. An
      understanding of the conditions under which these channels develop makes it
      possible either to avoid their formation or, alternatively, to enhance the number
      of channels in order to encourage proliferating cells to grow in radial columns,
      rather than in a less organized pattern characteristic of most culture systems.

PMID- 9542650
TI  - A simplified model of hypoxic injury in primary cultured rat hepatocytes.
AB  - The Anaeropack system for cell culture, which was originally designed for the
      growth of anaerobic bacteria, was used to produce a hypoxic atmosphere for
      cultured hepatocytes. We measured changes in the oxygen and carbon dioxide
      concentrations and the atmospheric temperature in an airtight jar. We also
      measured changes in the pH of the medium during hypoxia to assess the accuracy of
      this system. Moreover, we used three durations (2, 3, and 4 h) of hypoxia and 8 h
      of reoxygenation in cultured rat hepatocytes, and then measured the lactate
      dehydrogenase (LDH), ketone body concentration (acetoacetate + beta
      hydroxybutyrate), and the ketone body ratio (KBR: acetoacetate/beta
      hydroxybutyrate) in the medium in order to assess the suitability of this system
      as a model for reperfusion following liver ischemia. The oxygen concentration
      dropped to 1% or less within 1 h. The concentration of carbon dioxide rose to
      about 5% at 30 min after the induction of the hypoxic conditions, and was
      maintained at this level for 5 h. No effect of the reaction heat produced by the
      oxygen absorbent in the jar was recognized. The extent of cell injury produced by
      changing the hypoxic parameters was satisfactorily reflected by the KBR, the
      ketone body concentration, and the LDH activity released into the medium. Because
      this model can duplicate the conditions of the hepatocytes during
      revascularization following ischemic liver, and the Anaeropack system for cell
      culture is easy to manipulate, it seems suitable for the experimental study of
      hypoxic injury and revascularization in vitro.

PMID- 9542651
TI  - Evaluation of metanephric maturation in a human fetal kidney explant model.
AB  - We have developed a unique human fetal kidney explant model to study the role of
      the insulin-like growth factor (IGF) system in metanephric development. Kidneys
      from 10-18 wk gestation human abortuses were maintained in serum-free conditions
      and defined medium, which was shown to support the induction and differentiation
      of the viable metanephric blastema. Histologically the tissue remained viable to
      192 h of serum-free culture, while metanephric differentiation, reflected by a
      shrinking nephrogenic zone and the formation of maturing S-shape and glomerular
      forms, was accelerated and occurred between 48 and 96 h. In the nephrogenic zone,
      a significant decrease in IGF-II gene expression occurred, which reflected the
      differentiation of the metanephric blastema cell mass, IGF-II expression
      persisted, however, in the expanded interstitial mesenchyme. With differentiation
      over 48 h an increase in IGFBP-2 and WT1 gene expression by Northern blot
      analysis occurred, and was localized by in situ hybridization to the
      differentiating glomerular epithelial cell mass. Analysis of the explant
      conditioned media by Western ligand blot demonstrated an increase in the rate of
      IGF binding protein (IGFBP)-2 peptide production by the differentiating explant,
      consistent with an increase in IGFBP-2 gene expression and with metanephric
      differentiation. This pattern of temporal and spatial gene expression closely
      approximates that of normal in vivo fetal renal development and of glomerular
      epithelial cell differentiation.

PMID- 9542652
TI  - Different characteristics of endothelial cells from central and peripheral human
      cornea in primary culture and after subculture.
AB  - Several methods for isolation and cultivation of human corneal endothelial cells
      have been described during the last few decades. In contrast to the situation in
      vivo, the cultured cells show mitogenic activity but often lose their typical
      morphological appearance. In this paper, we describe a technique to isolate and
      cultivate morphologically unchanged endothelium from the human cornea. This
      method revealed different characteristics of endothelial cells according to their
      position within the human cornea. Endothelial cells isolated from the central
      part have a morphology similar to that of cells in vivo (i.e., they are densely
      packed and show no mitogenic activity). In contrast, endothelial cells derived
      from the peripheral part of the cornea are characterized by mitogenic activity
      but their cell-to-cell attachment seems to be less tight than in vivo. The
      significance of these two different endothelial cell types for wound healing in
      the human cornea is discussed.

PMID- 9542653
TI  - Transient inhibition of L929 cell mitosis and locomotion by argon ion laser
      irradiation.
AB  - Argon ion laser irradiation of L929 cells transiently inhibits both entry into
      and passage through mitosis without affecting clonogenic survival. Anaphase
      mitotic figures virtually disappear from irradiated cell monolayers although
      prophase + metaphase mitotic figures can still be identified. The total number of
      mitotic figures does not change significantly and time-lapse video recording
      shows that cells do not enter mitosis following irradiation. This effect is
      dependent on light dose within the 900-2700 J/cm2 range and persists for 10-48 h
      depending on the initial light exposure. Inhibition of cell locomotion and
      subsequent recovery were observed to occur over a similar time course. The
      possible contribution of these phenomena must be considered whenever biological
      systems are exposed to argon ion laser irradiation.

PMID- 9542654
TI  - Rapid, fluorometric DNA determination for chick limb-bud mesenchymal-cell
      microcultures.
AB  - Micromass cultures of chick and mouse limb-bud mesenchymal cells are commonly
      used for in vitro studies of cellular differentiation. Previously, adaptation of
      these cultures to 96-well plates facilitated analyses of various aspects of
      cellular behavior and the effects of different media components in these
      cultures. These adjustments allowed development of a serum-free medium for chick
      limb-bud mesenchymal cells and substantially decreased costs associated with
      media and reagents. Here we report a further development for this model system; a
      Hoechst 33342-based in situ DNA assay that provides reliable data much more
      quickly and with considerably less effort than had been feasible in the past.
      Because it allows quantitation of products of cellular differentiation and DNA in
      the same cultures, the number of cultures needed to provide the same data is
      essentially halved and the accuracy of normalized values for quantitative
      estimates of markers of differentiation is improved. Studies of the effects of
      retinoic acid on chick limb-bud mesenchymal cells were performed to document the
      usefulness of this method.

PMID- 9542655
TI  - The time-pattern of rises and falls in proliferation fades with senescence of
      mortal lines and is perpetuated in immortal rat hepatoma Fao cell line.
AB  - Immortal cells perpetuate the rises and falls of proliferation that are
      progressively damped in mortal long-term cultured cells. For immortal rat
      hepatoma Fao cells, similar waves of proliferation occurred about every 3-4 wk.
      Under the same conditions, embryonic human fibroblasts and transformed but not
      immortalized embryonic fibroblasts display similarly recurring proliferation
      waves that progressively decrease in amplitude until senescence of the lines. In
      addition, strains of diploid normal human skin fibroblasts cultured under
      different culture conditions display a similar time-pattern of proliferation.
      Although the amplitude and baseline of these fluctuations are characteristic for
      each cell line, a common point was marked slow down in proliferation after every
      sequence of about 25 population doublings for all cells. Renewed proliferation
      waves of Fao cells allow about 22-23 additional population doublings each. Normal
      embryonic fibroblast culture and its transformed counterpart accumulate about 30
      and 60 population doublings, respectively, before senescence. Normal fibroblast
      strains accumulate about 25 population doublings over their entire life spans.
      This halt in proliferation after every stretch of about 25 population doublings
      may correspond to a structural or functional stop following attrition of
      telomeric DNA. This putative stop may be bypassed once in transformed embryonic
      cells and repetitively in immortal cells. In support of this hypothesis, we
      observed rapid telomere shortening, in two steps, during divisions of mortal
      embryonic cells, and maintenance of long telomeres in immortal Fao cells, which
      may indicate episodic repair of telomeres. Alternatively, such maintenance of
      long telomeres may reflect survival and successive clonal growth of rare cells
      with long telomeres. We suggest that the balance between telomere attrition and
      repair processes regulates the waves of proliferation.

PMID- 9542656
TI  - The presence of transcription factors in fetal bovine sera.
AB  - Three sources of fetal bovine serum (FBS) were fractionated by ammonium sulfate
      precipitation and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE), transferred to Immobilon-P membranes, immunoblotted with a panel of
      transcription factor antibodies, and detected by enhanced chemiluminescence. Nine
      transcription factors were detected--ATF-2, SRE-ZBP, GATA-2, TFIID, Ets-1/Ets-2,
      E2F-1, Oct-2, p53, and AP-2; four transcription factors were not detected--Myo D,
      CREB, Sp2, and Wilms' tumor. The results indicated the presence of varying
      amounts of several transcription factors in three commercial sources and may
      represent heretofore unrecognized factors influencing cell culture.

PMID- 9542657
TI  - Apoptosis in the chick wing bud and the permanence of FGF-2 rescue.
AB  - Two regions of programmed cell death that occur in the mesoderm of developing
      chick wing buds were studied in vitro. The opaque patch (OP) and posterior
      necrotic zone (PNZ) were examined for the presence of internucleosomal DNA
      degradation and for rescue by protein synthesis inhibition, two defining
      characteristics of apoptosis. Agarose gel electrophoresis showed that DNA from OP
      and PNZ tissue was cleaved into nucleosome size pieces and this cleavage was
      prevented by inhibition of protein synthesis with cycloheximide. Both regions
      showed rescue with cycloheximide as determined by the chromium release assay and
      examination of electron micrographs. Also, the permanence of basic fibroblast
      growth factor (EGF-2) rescue in the OP and NPZ was examined using the chromium
      release assay. While rescue in the OP was found to be permanent, rescue in the
      PNZ only delayed death while FGF-2 was present in the culture medium. This
      research shows that death in the OP and PNZ exhibits internucleosomal DNA
      fragmentation and is prevented by inhibition of protein synthesis with
      cycloheximide, biochemically characterizing this death as apoptosis. It also
      suggests that in vitro FGF-2 rescue is permanent in the OP but is merely a delay
      of cell death in the PNZ.

PMID- 9542658
TI  - Topography of amphiregulin expression in cultured human keratinocytes:
      colocalization with the epidermal growth factor receptor and CD44.
AB  - Much of the autonomous growth of cultured keratinocytes is attributable to the
      signaling of amphiregulin, a heparin-binding autocrine growth factor, through the
      epidermal growth factor receptor. Emerging evidence suggests, moreover, that the
      membrane proteoglycan, CD44, is a cofactor for the interaction of heparin-binding
      ligands with their receptors. This model was evaluated by characterizing the
      patterns of the immunolabeled molecules in cultured human neonatal keratinocytes,
      to test the hypothesis that involvement in a common function results in
      coordinate segregation within or on the cell. The molecules were localized by
      double immunofluorescence labeling to detect amphiregulin and either the
      epidermal growth factor receptor or CD44, and the immunostained products were
      imaged by scanning laser confocal microscopy. Both amphiregulin and the epidermal
      growth factor receptor segregated to a perinuclear distribution and to
      intercellular contacts. In addition, amphiregulin localized to the outer leading
      edge of colonies and focally to intranuclear sites. Metabolic blockade of
      proteoglycan sulfation with sodium chlorate inhibited growth of the cells and
      concurrently enhanced the nuclear, but decreased the outer leading edge, labeling
      for amphiregulin. There was no nuclear or perimeter labeling for the epidermal
      growth factor receptor. Cultures co-immunolabeled for CD44 and amphiregulin
      exhibited variable perinuclear staining for both, but otherwise CD44 was
      distributed to intercellular contacts. The intercellular localizations of CD44
      with amphiregulin and of amphiregulin with the epidermal growth factor receptor
      were strongly concordant. These data are consistent with a concerted function at
      intercellular contacts, where cytokine signaling is mediated via receptor binding
      and possibly regulated by the CD44 proteoglycan as cofactor. The intranuclear and
      perimeter labeling of amphiregulin, however, suggests that this cytokine has
      additional functions, both in the nucleus and as a matrix receptor.

PMID- 9542659
TI  - The role of hepatocyte growth factor (HGF) at progressive stages of metanephric
      development.
AB  - Several lines of evidence suggest that hepatocyte growth factor (HGF), a soluble
      protein secreted by mesenchymal cells, may elicit a morphogenic response in the
      developing metanephros. We investigated the role of HGF at three different stages
      of murine metanephric development utilizing serum-free organ culture. Cultures
      were initiated at E-13, E-15, and E-17; treated with exogenous HGF or antibodies
      to HGF (to block endogenous HGF) for 120 h in vitro; and evaluated for growth and
      differentiation in comparison to control explants cultured for 120 h in basal
      medium. HGF treatment of E-13 explants resulted in a reduction of growth and
      differentiation compared to control explants. Treatment of E-13 explants with
      antibodies to HGF produced explant growth and differentiation indistinguishable
      from control explants. In contrast to the results of E-13 cultures, explants
      initiated at E-15 and E-17 demonstrated an increased growth and differentiation
      profile when treated with HGF compared to controls. Treatment of E-15 and E-17
      explants with antibodies to HGF resulted in a decrease growth and differentiation
      profile compared to control or HGF-treated explants. These data demonstrate that
      HGF has differential effects on renal morphogenesis at progressive developmental
      stages of metanephric development.

PMID- 9542660
TI  - Immunology of HPV infection and HPV-associated tumors.

PMID- 9542661
TI  - Acne inversa.

PMID- 9542662
TI  - Spontaneous course of hemangiomas: facts and speculations.

PMID- 9542663
TI  - Erythroderma: a clinico-etiologic study of 90 cases.
AB  - BACKGROUND: The difficulty with erythroderma lies in finding the underlying
      cause. Almost all the published original clinical series of erythroderma
      originate from western countries. Our aim was to evaluate various causes of
      exfoliative dermatitis in our community and compare the findings with previous
      studies. METHODS: Ninety patients with erythroderma of either sex and any age,
      were studied at the Dermatology Department, Mayo Hospital, Lahore, Pakistan,
      between April 1992 and May 1995. A through clinical examination and relevant
      laboratory investigations, including skin biopsies, were performed. RESULTS: The
      mean age of onset was 41.6 years with a male:female ratio of 2.8:1. The onset was
      acute in 69% of patients. The salient features included nail changes (80%),
      mucosal involvement (36.6%), alopecia (30%), islands of normal skin (14.4%), and
      the "deck chair sign" (5.5%). The most frequent cause of erythroderma was pre
      existing dermatoses (74.4%), including psoriasis (37.8%), dermatitis (12.2%),
      ichthyoses (7.8%), and pemphigus foliaceus (5.6%). Drugs and malignancy each
      induced erythroderma in 5.5% of cases. No cause could be found in 14.6% of cases.
      CONCLUSIONS: Etiologically, pre-existing dermatoses showed the highest incidence
      and drugs the lowest compared with previous studies. Dermatitis was less common.
      There was a greater variety of causes of erythroderma in our series. Hair and
      nails were more frequently involved. Mucosal involvement, not mentioned in other
      studies, was present in 36.6% of our cases. The "deck chair sign" and islands of
      normal skin were seen in dermatoses not reported previously.

PMID- 9542664
TI  - Sweet's syndrome without granulocytosis.
AB  - BACKGROUND: Sweet's syndrome (SS), acute febrile neutrophilic dermatosis, has
      been linked to hematologic malignancies and presents with characteristic
      edematous dermal plaques. Peripheral blood neutrophilia is frequently seen in
      association with SS and is one of the diagnostic criteria. OBJECTIVE: To report
      the clinical, laboratory, and hematologic data of four patients with myeloid
      leukemia who developed SS after chemotherapy. Three of these patients were
      neutropenic. METHODS: A retrospective study of four patients with SS and
      hematologic malignancies was undertaken. Three patients had de novo acute
      myelogenous leukemia and one was in the acute blast crisis of chronic myelogenous
      leukemia. RESULTS: Sweet's syndrome was not originally suspected in these
      patients because of the low peripheral white blood cell counts caused by
      chemotherapy. All of the patients presented with fevers, arthralgias, and an
      eruption. They had been treated with antibiotics because of a presumed infection.
      Once the correct diagnosis was made and oral prednisolone was started, a rapid
      response followed. CONCLUSIONS: Sweet's syndrome should be considered in the
      differential diagnosis when acute myeloid leukemic patients develop skin lesions
      and unexplained fevers regardless of the peripheral blood counts.

PMID- 9542665
TI  - Diabetic dermopathy and internal complications in diabetes mellitus.
AB  - BACKGROUND: Diabetic dermopathy is the most common cutaneous marker of diabetes
      mellitus. The relationship of diabetic dermopathy to internal complications of
      diabetes mellitus, such as nephropathy, retinopathy, and neuropathy, is still
      unknown. METHODS: The possible role of diabetic dermopathy as a clinical sign of
      internal complications in diabetes mellitus was investigated. One hundred and
      seventy-three patients with diabetes mellitus, of whom 125 (72%) had insulin
      dependent diabetes mellitus and 48 (28%) had non-insulin-dependent diabetes
      mellitus, were studied. RESULTS: Diabetic dermopathy was present in 69 (40%) of
      patients, statistically more significant in patients 50 years of age and older.
      The mean diabetic duration was significantly higher in patients with diabetic
      dermopathy than in those without. The associations of diabetic dermopathy with
      retinopathy, nephropathy, and neuropathy were each statistically significant, and
      the increased frequency of diabetic dermopathy correlated with an increased
      number of these three complications in each patient. CONCLUSIONS: Some of the
      factors that affect the development of internal complications in diabetes
      mellitus may play a role in the development of diabetic dermopathy, and diabetic
      dermopathy may serve as a clinical sign of an increased likelihood of these
      internal complications in diabetic patients.

PMID- 9542666
TI  - Immunophenotypic analysis of normal human dendritic cells isolated from epidermis
      and dermis.
AB  - BACKGROUND: The skin immune system comprises two types of dendritic cells, i.e.
      CD1a-positive Langerhans cells in the epidermis and CD36-positive dendritic
      macrophages in the dermis. Dendritic cells can migrate from skin explants into a
      culture medium. METHODS: We have examined the morphology and immunophenotype of
      the dendritic cells migrating from epidermal and dermal sheets in vitro. The
      epidermis and dermis of keratomes of normal human skin were separated with
      dispase and cultured for 72 h. At this time, the non-adherent cells in the medium
      were removed, enriched on a metrizamide or Lymphoprep gradient, counted, prepared
      by cytospin, and labeled for CD1a, CD36, and HLADr. RESULTS: Cells migrating from
      the epidermis and dermis show many thin projections or a few veils from the cell
      surface. Approximately four times more cells migrate from epidermal than dermal
      sheets from the same keratome. CONCLUSIONS: Using methods to separate the
      epidermis from the dermis, both CD1a-positive Langerhans cells and CD36-positive
      dendritic macrophages can be obtained from both tissues, although in different
      numbers.

PMID- 9542667
TI  - Wound healing in Behcet's syndrome.
AB  - BACKGROUND: Because there is an increased inflammatory response to trauma,
      particularly of the skin, in patients with Behcet's syndrome (BS), an alteration
      in wound healing in BS is expected. The aim of this study was to investigate the
      healing features of punch biopsy wounds in BS and acne vulgaris (AV) patients
      used as controls. METHOD: Full-thickness skin punch biopsies (4 mm) were taken
      from the hairless sites of the non-dominant forearms in 20 BS and 20 AV patients.
      Each patient was examined on days 1, 2, 3, 4, 5, 8, and 10, and the biopsy wound
      area and induration were marked on sterile glass slides. Other inflammatory
      changes, such as suppuration and pain, were also recorded. No antiseptic
      solutions or ointment, except saline, were used. RESULTS: The wound area healed
      similarly in both groups (p > 0.05). Thirteen (65%) BS patients had erythematous
      haloes around the wound on the first day. The number of patients presenting
      inflammatory changes reached 18 (90%) on the second day in the BS group. The area
      of erythema around the wound in BS patients was significantly greater than that
      in AV patients (5; 25%). It gradually decreased day by day. Purulent changes were
      observed in four BS patients on day 1, and induration around the biopsy wound in
      six patients on day 2. Only one patient with AV had suppuration, which appeared
      on the second day, while no AV patient displayed induration. CONCLUSION: Biopsy
      induced trauma may cause increased inflammation in BS, but wound healing is not
      altered.

PMID- 9542668
TI  - Protein C and protein S activities in Behcet's disease as risk factors of
      thrombosis.
AB  - BACKGROUND: In Behcet's disease (BD), there is a marked increase in vascular
      complications. Approximately 30% of patients with BD suffer from thrombosis of
      the arteries and veins, varices, aneurysms, and thrombophlebitis of superficial
      or deep veins. Protein C and Protein S are major inhibitors of coagulation, and
      it is well known that the deficiency of Protein C and Protein S causes thrombotic
      disorders. METHODS: Protein C and Protein S activities were measured in 23
      patients with BD and in a control group consisting of 23 age- and sex-matched
      healthy volunteers. Patients who had received anticoagulant or oral contraceptive
      drugs, or who had liver disease or active thrombosis, were not included in the
      study. RESULTS: Of the 23 patients with BD (age, 13-55 years), the mean Protein S
      activities (94.2 +/- 11.3%) were slightly lower than the means of the control
      group (109.1 +/- 8.4%), but not statistically significant differences could be
      demonstrated (p > 0.05). Compared with the means of the control group (103.5 +/-
      6.9%), the Protein C activities were not lower in BD (106.3 +/- 8.4%). No
      statistical difference was determined. CONCLUSIONS: Protein C and Protein S
      deficiencies are not a probable cause of thrombotic manifestations in BD. We do
      not recommend the measurement of these activities routinely in BD unless
      thrombosis is the major and primary manifestation of BD.

PMID- 9542669
TI  - Malignant blue nevus of the scalp.
AB  - A 70-year-old woman had noticed, at the age of 30, a single blue nodule of about
      1 cm in size on her scalp. The lesion remained stable until 1991, when it became
      larger and ulcerated and, because of the sudden onset of additional macules and
      nodules around it, the patient presented at our Dermatological Division in August
      1992. Physical examination showed a blue-black plaque, 2 x 2 cm in size, on the
      left parietal area of the scalp, surrounded by several blue-grey pigmented
      nodules and macules (Fig. 1). Chest X-ray, abdomen scan, and a total body
      computed tomography (CT) scan were negative for metastatic disease. A wide
      resection of the scalp lesion was performed. The histologic evaluation revealed a
      dense collection of spindled melanocytes in the dermis and in the subcutaneous
      fat. Nuclear and cytoplasmic pleomorphism, some mitotic figures, and necrosis
      foci were present (Figs 2 and 3). Pictures of cellular blue nevus were found in
      the surrounding lesions. Ten months later, new blue macular and papular lesions
      appeared in proximity to the surgical scar. The patient refused any additional
      surgery, and so was treated with dacarbazine (DTIC) 800 mg intravenously (every
      20 days) and 2 alpha interferon (3 million units subcutaneously, three times
      weekly). The growth of the lesions slowed down for a few weeks, and then
      increased again to become a wide, blue-black vegetating mass (Fig. 4). In June
      1995, a total body CT scan revealed multiple focal nodules on the lungs and two
      metastatic masses on the eighth segment of the liver. A palliative
      polychemotherapy, with vindesin 3 mg/m2 and DTIC 400 mg/m2, was started, but did
      not stop the progression of the disease, and the patient died in December 1996.

PMID- 9542670
TI  - Well-differentiated squamous cell carcinoma of the penis associated with HPV type
      33.

PMID- 9542671
TI  - Flexural purpura and Epstein-Barr virus infection.

PMID- 9542672
TI  - Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) presenting as
      a fever of unknown origin in an infant.

PMID- 9542673
TI  - Kwashiorkor/zinc deficiency overlap following partial gastrectomy.

PMID- 9542674
TI  - Cutaneous bronchogenic cysts.

PMID- 9542675
TI  - Short-term itraconazole versus terbinafine in the treatment of tinea pedis or
      manus.
AB  - A total of 304 patients with a clinical diagnosis of palmar-type tinea pedis or
      manus and a positive mycologic examination were recruited into this double-blind,
      randomized, multicenter, phase III study. Patients were randomized to receive
      either oral itraconazole 200 mg twice daily (in the morning and evening) for 7
      days, followed by placebo for 7 days (n = 153), or placebo in the morning and
      oral terbinafine 250 mg in the evening for 14 days (n = 151). At the first visit
      and 1, 2, and 6 weeks after the start of the study, signs and symptoms were
      assessed clinically, and scales were taken for mycologic assessments (microscopy
      and culture). At weeks 1, 2, and 6, the effectiveness of therapy was evaluated
      globally and given a rating of healed (absence of signs and symptoms), marked
      improvement (> or = 50% clinical improvement), considerable residual lesions (<
      50% clinical improvement), no change, or worsened. The primary efficacy parameter
      was the mycologic cure rate at the follow-up end-point (week 6). The tolerability
      of the study medications was assessed at weeks 1 and 2. Adverse events were
      recorded at weeks 1, 2, and 6. Routine hematologic and biochemical tests were
      performed at the start of the study and after 1 week of treatment. No significant
      differences were seen in the baseline patient characteristics between the two
      groups. The rate of mycologic cure (negative microscopy and culture test result)
      was 79% in the itraconazole group and 80% in the terbinafine group at the follow
      up end-point. The analysis of the 90% confidence interval for the difference
      between the treatment groups (-7.1, 5.4) and the outcome of the Blackwelder test
      (for two one-sided tests, P = 0.013 and P = 0.029) showed the two treatments to
      be equivalent. The results of the global evaluations of the efficacy in the two
      treatment groups are shown in Table 1. The rate of clinical response (healed or
      markedly improved) was 93% in the itraconazole group and 91% in the terbinafine
      group at the follow-up end-point. The analysis of the 90% confidence interval for
      the difference between the two groups (-2.5, 5.7) and the outcome of the
      Blackwelder test (for two one-sided tests, P = 0.004 and P < 0.001) showed the
      two treatments to be equivalent. The severity of the clinical signs and symptoms
      decreased from the baseline to the treatment end-point and from the treatment end
      point to the follow-up end-point in both groups. At the double-blind treatment
      period end-point (week 2), the tolerability of the study medication was rated as
      very good or good in more than 97% of patients. During treatment, 21 of 153
      patients (14%) in the itraconazole group and 28 of 151 patients (19%) in the
      terbinafine group reported adverse events. During follow-up, one patient in the
      itraconazole group and two in the terbinafine group reported adverse events. The
      most frequent events were headache, abdominal pain, nausea, vomiting, and
      hypertriglyceridemia. Two patients in the itraconazole group and four in the
      terbinafine group withdrew because of adverse events. Severe adverse events were
      reported by one patient in the itraconazole group and five in the terbinafine
      group. Serious adverse events were reported by two patients in the terbinafine
      group, although these were probably not drug related. No clinically relevant
      changes in laboratory variables were observed.

PMID- 9542676
TI  - Clobetasol propionate emollient 0.05% in the treatment of atopic dermatitis.
AB  - A 4-week, double-blind, randomized clinical trial, comparing the efficacy and
      safety of clobetasol propionate emollient cream 0.05% and its vehicle, was
      conducted at four private dermatology clinics in 81 non-hospitalized patients (>
      or = 12 years old) with moderate-to-severe atopic dermatitis covering 2% or more
      of their body surface. All patients had at least one lesion 2 cm or more in
      diameter. Three signs/symptoms of target lesions (erythema, pruritus, and
      induration/papulation) were scored by investigators on a scale of 0-3 (in 0.5
      point increments; 0 = absent, 1 = mild, 2 = moderate, and 3 = severe); the total
      of the three scores had to be > or = 6 for patients to qualify for study entry.
      Patients were excluded if they were immunocompromised, pregnant, or nursing; had
      skin atrophy, telangiectasia or striae in skin areas to be treated; or had
      received topical treatments for atopic dermatitis within 1 week prestudy,
      intramuscular triamcinolone within 6 weeks prestudy, or long-term systemic
      corticosteroid usage within 6 months prestudy. Patients were randomized in a 1:1
      ratio to receive either clobetasol propionate emollient 0.05% twice daily (n =
      41), or the emollient vehicle twice daily (n = 40), for 4 weeks. A fingertip
      unit, equaling approximately 0.5 g in males and 0.43 g in females (enough to
      cover approximately 2% of the body), was used to measure and apply a thin film of
      study drug to the affected areas. The efficacy was evaluated by investigators and
      patients on days 4, 8, 15, and 29 after initiation of therapy, and 2 weeks after
      the end of treatment (day 43). Investigators performed a physician's gross
      assessment based on the percentage improvement of the target lesion. They also
      rated changes from baseline in mean severity scores for six individual
      signs/symptoms (erythema, pruritus, induration/papulation, lichenification,
      erosion/oozing/crusting, and scaling/dryness) and for total signs/symptoms
      according to the severity scoring system described above. Patients rated their
      response to treatment as excellent, good, fair, poor, or worse. Laboratory
      assessments were made on days 15, 29, and (if necessary) day 43.

PMID- 9542678
TI  - The first 'rules' of an ancient dermatologic hospital, the S. Gallicano Institute
      in Rome (1725).

PMID- 9542677
TI  - Epidemiology and in vitro activity of antimycotics against candidal
      vaginal/skin/nail infections in Singapore.
AB  - BACKGROUND: Candidal infections of the skin/nails and vagina are very common
      worldwide. Various in vitro test systems are available to help to determine the
      antifungal activity of drugs. The minimum inhibitory concentration (MIC) is a
      standard measure of the in vitro potency of drugs against yeasts. METHODS:
      Vaginal smears and skin/nail scrapings of 50 consecutive patients with candidal
      vaginitis and 46 consecutive patients (28 women, 18 men) with cutaneous/nail
      candidosis were used in the study. Direct microscopy and culture from vaginal
      smears and skin scrapings were performed on all patients. The MICs were
      determined using the broth dilution method. RESULTS: For vaginal candidosis, the
      mean age of the patients was 28.2 years (range, 9-49 years). Candida albicans
      accounted for 58% of the isolates, C. glabrata for 32%, C. tropicalis for 6%, and
      C. parasilosis for 4%. At the MIC of < or = 4 mg/L, 65-95% of C. albicans, 66-94%
      of C. glabrata, 33-100% of C. tropicalis, and 0-50% of C. parasilosis were
      susceptible to the drugs tested (ketoconazole, itraconazole, nystatin,
      amorolfine, clotrimazole, and miconazole). For cutaneous/nail candidosis, the
      mean age of the patients was 45 years (range, 19-82 years). C. albicans made up
      59% of the isolates, C. parasilosis 20%, C. krusei 13%, C. glabrata 4%, and C.
      tropicalis 4%. At the MIC of < or = 4 mg/L, 59-96% of C. albicans, 100% of C.
      glabrata, 83-100% of C. krusei, 89-100% of C. parasilosis, and 100% of C.
      tropicalis were susceptible to the drugs tested (ketoconazole, itraconazole,
      nystatin, amorolfine, clotrimazole, and miconazole). CONCLUSIONS: C. albicans is
      the most common Candida species causing cutaneous/nail and vaginal candidosis in
      Singapore. The in vitro antifungal activities of ketoconazole, itraconazole,
      nystatin, amorolfine, clotrimazole, and miconazole are similar against the
      various Candida species. C. parasilosis in vaginal candidosis appears to be less
      susceptible. Here, itraconazole and amorolfine may be more effective.

PMID- 9542679
TI  - Peculiar dyschromic changes of finger nails in a patient with multiple system
      atrophy.

PMID- 9542680
TI  - Bowen's disease of the palm.

PMID- 9542681
TI  - Pemphigus Area and Activity Score (PAAS)--a novel clinical scoring method for
      monitoring of pemphigus vulgaris patients.

PMID- 9542682
TI  - Lichen planus developing on the border of tinea corporis.

PMID- 9542683
TI  - Evaluation of the alleviative action of neurotropin for penile pain associated
      with intracavernous injection of prostaglandin E1 assessed using the visual
      analogue scale.
AB  - We examined whether penile pain associated with intracavernous injection of PGE1
      could be alleviated with a intracavernous injection of neurotropin, a non
      protein, bioactive agent extracted from skin tissue with inflammation elicited by
      the Vaccinia virus. Twenty-three patients with erectile dysfunction were enrolled
      in this study. They were divided into two groups. The first group was allocated
      20 micrograms of PGE1 alone first, followed by PGE1 plus 1.5 ml of neurotropin
      after two weeks. The second group was allocated PGE1 plus 1.5 ml of neurotropin
      first, followed by PGE1 alone after two weeks. Pain was evaluated by the visual
      analogue scale (VAS). In the 17 patients reporting discomfort, pain scores for
      PGE1 injection with neurotropin were significantly lower than those without
      neurotropin. No patients showed local or systemic complications that might be
      related to neurotropin. From these data we conclude that neurotropin may be an
      effective and safe drug for penile pain associated with PGE1 intracavernous
      injection.

PMID- 9542684
TI  - Drop-out reasons and complications in self-injection therapy with a triple
      vasoactive drug mixture in sexual erectile dysfunction.
AB  - The usefulness, complications and reasons for discontinuing the self-injection
      program with a combination of papaverine, phentolamine and prostaglandin E1 were
      evaluated in 189 patients (mean age 57.2 y), who were included from April 1993 to
      September 1995 (mean follow-up 10.25 months). Patients were split into two
      groups: Active, those who continued with the program (48%); and Inactive, those
      who discontinued treatment or failed to attend consultation after five months
      from the last visit (52%). Only 30% of the inactive group reported failure to
      achieve response with the self-injected doses. Fibrosis in 5.3% and prolonged
      erection in 3.7% were the most severe complications. Patients lacking organic
      pathology showed a clear tendency to reduce the drug dose during treatment,
      recover spontaneous erections and discontinue the program for reasons unrelated
      to drug efficacy. The triple drug mixture provides an effective alternative in
      the treatment of impotence, with a low rate of complications.

PMID- 9542685
TI  - Alternative approaches to the management of priapism.
AB  - Herein we describe the use of intracavernous methylene blue (MB), a guanylate
      cyclase inhibitor, or internal pudendal artery embolization for the treatment of
      priapism. Eleven patients with priapism were treated from 1993-1996. Etiologies
      of priapism included PGE1/papaverine (3), trazodone (2), and sickle cell disease
      (1), in the other five cases the causes the cause was unknown. The average
      duration of priapism was 27 h for all patients (6-72 h). Five patients who failed
      intracavernous MB or an alpha-adrenergic agonist, underwent unilateral or
      bilateral pudendal artery embolization. The average duration of priapism for
      patients undergoing embolization was 43 h. Sixty-seven percent of the patients
      treated with MB responded with immediate detumescence. One-hundred percent of
      patients with priapism secondary to intracavernous injection therapy or trazodone
      responded. Of the five patients who underwent embolization, 40% achieved
      immediate pain relief and subsequent detumescence. The three non-responders
      exhibited a partial detumescence over 47-72 h. After follow-up of one year
      embolization available for only two patients revealed that one regained potency
      while the other remained impotent. These results confirmed that MB is effective
      for pharmacologically-induced priapism. Embolization is a less invasive option
      for refractory priapism, although results are less than satisfactory in men with
      priapism of several days duration.

PMID- 9542686
TI  - Engineering analysis of penile hemodynamic and structural-dynamic relationships:
      Part I--Clinical implications of penile tissue mechanical properties.
AB  - PURPOSE: The least investigated physical determinant of penile rigidity has been
      penile tissue material properties. The goals in this study (Part I) were to
      define two penile mechanical parameters, cavernosal expandability X and tunical
      distensibility VE/VF, determine their magnitudes in humans and develop an
      analytical expression for penile volume as a function of these two tissue
      characteristics and intracavernosal pressure. METHODS: Dynamic infusion
      pharmacocavernosometry was performed in 21 impotent patients (age 43 +/- 19 y) to
      provide human geometric, hemodynamic and structural data. A mathematically
      derived model of hemodynamic and structural-dynamic characteristics of penile
      erection was developed (Parts I, II, III) incorporating penile tissue mechanical
      qualities. RESULTS: Cavernosal expandability X provided a measure of the ability
      to approach maximum volume at relatively low intracavernosal pressures. Tunical
      distensibility VE/VF denoted the maximal erect to flaccid penile volume ratio.
      The magnitudes of X and VE/VF in the study population were 0.04-0.17 mmHg-1 and
      1.7-5.0 respectively. CONCLUSIONS: Enabling penile volume to be derived as a
      function of tissue mechanical characteristics and pressure, allows for penile
      rigidity to be expressed (in Part II) as a function of pressure, geometry and
      tissue qualities.

PMID- 9542687
TI  - Engineering analysis of penile hemodynamic and structural-dynamic relationships:
      Part II--Clinical implications of penile buckling.
AB  - PURPOSE: Penile buckling force was analytically described in terms of its
      constituents. In addition, theoretically-derived buckling force data were
      compared to clinically measured data and the influence of each constituent on
      penile buckling force data was assessed. METHODS: Using engineering buckling
      theory for a column, a mathematically-derived penile buckling model was developed
      which incorporated geometric and hemodynamic data obtained by dynamic infusion
      pharmacocavernosometry studies in 21 impotent patients (age 43, range 24-62 y) as
      well as penile tissue mechanical characteristics previously developed (Part I).
      RESULTS: In 17 of 21 patients the mean difference between theoretically derived
      and clinically measured buckling force data was 0.33 +/- 0.25 kg (r = 0.96).
      Factors which increased penile buckling forces were: (1) high intracavernosal
      pressure values (rigidity was related to pressure in an exponential-like
      fashion); (2) high penile aspect ratio (D/L) values (relatively large
      diameter/short length penile geometry) and high flaccid diameter; and (3) high
      cavernosal expandability values (a measure of the ability of the corpora to
      approach its erect volume with relatively low intracavernosal pressures).
      CONCLUSIONS: Pressure-volume data (pressure, geometry and tissue characteristics)
      obtained during erectile function testing have been shown, for the first time, to
      theoretically predict the magnitude of clinically-measured penile buckling
      forces.

PMID- 9542688
TI  - Effect of Korean red ginseng on the rabbit corpus cavernosal smooth muscle.
AB  - The extracts of Korean red ginseng (EKG) is a complex mixture containing
      ginsenosides, polysaccharides, and several other products. Animal experiments
      have shown that the intravenous administration of extract of ginseng reduces
      blood pressure. Recently, it has been reported that ginseng has a relaxing effect
      on vascular smooth muscle and that the relaxation is associated with nitric oxide
      (NO) released from the vascular endothelium. The present study was undertaken to
      investigate the effects of EKG on isolated rabbit corpus cavernosal smooth muscle
      for evaluation of the possibility of developing EKG as an pharmacoerecting agent.
      Strips of rabbit corpus cavernosum were mounted in organ chambers to measure
      isometric tension. On the precontracted muscle strip with phenylephrine (PHE; 5 x
      10(-6) M), EKG began to exert a relaxing effect at the concentration of 1 mg/ml
      and the maximal relaxation effect was reached at 40 mg/ml in a dose-dependent
      manner. EKG was inhibited significantly by endothelial disruption and by
      pretreatment with methylene blue, pyrogallol, L-NNA or atropine. EKG partially
      inhibited the PHE (5 x 10(-6) M) induced contraction up to 45.67% of the control
      in a dose-dependent fashion. EKG decreased basal tension as well as inhibited the
      contraction induced by addition of CaCl2 (10(-3) M) dose-dependently in muscle
      strips at basal equilibrated state in Ca2+ free, high K+ depolarizing solution.
      EKG also inhibited the contraction induced by depolarization with 20, 40 and 60
      mM of KCl. However, this inhibitory effect did not occur with high concentrations
      of KCl (80 and 120 mM). EKG has a relaxing effect on the rabbit corpus cavernosal
      tissue in a dose dependent manner. The relaxation action of EKG is mediated by
      multiple action mechanisms that include increasing the release of NO from the
      corporal sinusoids, increasing intracellular calcium sequestration, and a
      hyperpolarizing action.

PMID- 9542689
TI  - Erectile dysfunction following Nd-YAG visual laser-assisted prostatectomy (VLAP).
AB  - We investigated if side fire Nd-YAG visual laser prostatectomy (VLAP) causes
      erectile dysfunction (ED) in patients who were sexually active prior to the
      procedure. The 36 study patients gave a detailed medical/sexual history: physical
      examination included bulbo-cavernous reflex (BCR) on rectal examination and
      routine blood tests. Lasing time, power of the applied laser beam (in watts),
      coagulation site and energy intensity were recorded. Patients with new onset ED
      during the one year study period underwent pudendal nerve conduction (PNC), color
      duplex Doppler ultrasonography, and NPT/RigiScan testing. In 6 out of 36 (16.7%)
      patients reporting significant post-operative ED, there was a tendency towards
      higher energy applied and longer lasing time but no correlation between prostate
      size or the site of energy application. Patients reported loss of night and/or
      morning erections (n = 5), retrograde ejaculations (n = 2), loss of ejaculate (n
      = 2), and decreased sensation of orgasm (n = 3). Three had abnormal PNC, duplex
      Doppler showed abnormal blood supply in four, and all six had abnormal
      NPT/RigiScan. We believe this is the first demonstration that VLAP may be
      associated with a high rate of ED and that the lasing time and intensity of
      applied laser energy may play a role in this outcome.

PMID- 9542690
TI  - Repetition of color Doppler ultrasonography: is it necessary?
AB  - The aim of the study was to determine whether any difference would occur in peak
      systolic velocity (PSV) and end diastolic velocity (EDV) measurements of color
      Doppler ultrasonography (CDU) between proximal and distal segments of the
      cavernous arteries obtained at different times. Twenty-six cases have undergone
      CDU three times in weekly intervals. PSV and EDV measurements of cavernous
      arteries were obtained both proximally and distally. The results have shown that
      statistically there was no difference between each measurement obtained on either
      sides at three different tests. (ANOVA PSV F(2-50) = 0.63, EDV F(2-50) = 0.81).
      Four of the 26 cases had different PSV results and six cases had different EDV
      results in three CDU tests. There was a statistical difference in measurements
      between proximal and distal segments of the cavernous arteries. (t-test t = 2.53,
      P = 0.015) In conclusion, repetition of CDU would not be necessary in majority of
      the cases. However investigators should always be aware and cautious about
      falsely abnormal results of CDU. Proximal segments of the cavernous arteries
      should be the site to obtain true CDU measurements.

PMID- 9542691
TI  - Percutaneous core biopsy of the penis.
AB  - To describe the efficacy of percutaneous core biopsy of penile corporal tissue,
      on ten impotent men, the biopsy was performed with a 19 and a 20 gauge core
      biopsy co-axial system using an automatic biopsy device. All biopsies were
      performed on an outpatient basis under local anesthesia. Adequate biopsy
      specimens were obtained in all. Percutaneous core biopsy of the penis is a safe
      procedure that is technically easy to perform.

PMID- 9542692
TI  - Transurethral alprostadil with MUSE (medicated urethral system for erection) vs
      intracavernous alprostadil--a comparative study in 103 patients with erectile
      dysfunction.

PMID- 9542693
TI  - Pediatric psychopharmacoepidemiology: an introduction.
AB  - The increased use of psychopharmacological agents in children and adolescents,
      the increased public debate about the possible adverse effects of these agents,
      and the growth of managed care have led to a burgeoning of interest in the
      pharmacoepidemiology of child psychiatric medications. This special issue of the
      Journal of Child and Adolescent Psychopharmacology reviews pharmacoepidemiology
      in child psychiatry. This introduction gives an overview of the articles that
      follow.

PMID- 9542694
TI  - An overview of three decades of research in pediatric psychopharmacoepidemiology.
AB  - Although psychotropic drugs are prescribed relatively often for childhood
      psychiatric and seizure disorders, relatively little is known about their use in
      everyday clinical settings--with the exception of children with ADHD and
      individuals with mental retardation. A legion of methodological and logistical
      obstacles are encountered when trying to gather information about pharmacotherapy
      for children, and this has often limited data collection to institutional
      settings or highly restricted geographic areas. Although initial efforts to study
      the extent of drug therapy focused primarily on the number of individuals
      receiving treatment and secondarily on drug dose, the breadth of topics quickly
      expanded to include numerous issues pertaining to the way psychotherapeutic
      agents are prescribed, evaluated, and monitored in typical clinical situations.
      This article presents an overview of treatment prevalence studies conducted
      during the past three decades and reviews a variety of clinical concerns raised
      by researchers in pediatric psychopharmacoepidemiology. The most salient findings
      from these studies are: (a) medication use continues to increase, (b) treatment
      prevalence rates in residential programs continue to be very high (40%-60%), and
      (c) many researchers continue to be concerned about the quality of treatment
      practices. The methodologies of this field show considerable promise for
      addressing pressing issues in health care for children and adolescents with
      emotional or behavioral disorders.

PMID- 9542695
TI  - Sources of data for pharmacoepidemiological studies of child and adolescent
      psychiatric disorders.
AB  - In view of the dramatic shift to managed care models for United States health
      care delivery, reliable information on the prevalence and variations in
      psychopharmacological drug therapies for youth in community practice settings is
      essential. Pharmacoepidemiology, the study of medication use in large
      populations, aims to accomplish that challenging task. This article offers child
      psychopharmacologists a brief introduction to data sources for
      pharmacoepidemiology. Knowledge of these data sources combined with
      epidemiological methods for data analysis is a beginning step to assess the
      psychotropic medication prescribing patterns of community physicians. This review
      is organized in the following sequence: (1) characteristics of the "usual
      practice environment" according to setting, patient population, and physician
      characteristics; (2) validity issues related to data sources and their potential
      for outcomes research; (3) data sources divided into primary and secondary types
      that are described in terms of their features, advantages, and limitations,
      followed by examples of selected applied studies using such information; (4)
      procedures for analyzing secondary data; (5) data analytic and longitudinal
      approaches; and (6) access, confidentiality, and funding. A goal for future
      investigators in this emerging field is to develop applied research that is
      clinically sophisticated, methodologically sound, and public health-minded.

PMID- 9542696
TI  - Psychopharmacoepidemiology of mental retardation: 1966 to 1995.
AB  - We present a brief historical overview of the prevalence studies of psychotropic
      drugs in individuals with mental retardation that were published between 1966 and
      1985, and a more comprehensive review of the prevalence studies from 1986 to
      1995. During the 1966 to 1985 period, typical prevalence rates of drug treatments
      in institutions (children and adults analyzed together) were found to range from
      30% to 40% for psychotropic drugs, 25% to 45% for anticonvulsants, and 50% to 70%
      for psychotropic and/or anticonvulsant drugs (i.e., psychotropics,
      anticonvulsants, or their combinations). In the community during the same period,
      prevalence rates in children were typically 2% to 7% for psychotropics, 12% to
      31% for anticonvulsants, and 18% to 33% for psychotropic and/or anticonvulsant
      drugs. For adults in the community, prevalence rates ranged from 26% to 36% for
      psychotropics, 18% to 24% for anticonvulsants, and 36% to 48% for psychotropic
      and/or anticonvulsant drugs. In contrast, during the 1986 to 1995 period, typical
      prevalence rates in institutions ranged from 12% to 40% for psychotropics, 24% to
      41% for anticonvulsants, and 44% to 60% for psychotropic and/or anticonvulsant
      drugs. In the same period, the prevalence rates in the community (for adults and
      children analyzed together) ranged from 19% to 29% for psychotropics, 18% to 23%
      for anticonvulsants, and 35% to 45% for psychotropic and/or anticonvulsant drugs.
      An analysis of the patterns of medication use showed that patient demographic,
      physical, social, behavioral, and psychiatric variables, as well as a number of
      staff variables, were correlated with use of pharmacotherapy in the entire
      population of individuals with mental retardation. A substantial number of
      individuals with mental retardation appeared to be prescribed psychotropic
      medications that may have been inappropriate for their diagnosis.

PMID- 9542697
TI  - Changing patterns of psychotropic medications prescribed by child psychiatrists
      in the 1990s.
AB  - The active (1994) and closed (1988 to 1992) outpatient records of youths seen in
      four separate community mental health centers (CMHC) in Baltimore County,
      Maryland were reviewed in mid-1994 to document recent changes in the medication
      prescribing practices of local child psychiatrists. Inpatient summaries of
      previously hospitalized CMHC youths were also reviewed to supplement the
      outpatient medication assessment with hospital data. This regional survey of
      medication treatments in child psychiatry revealed that, during the half decade
      before 1994, there was an increase in overall psychotropic medication treatment,
      multiple concurrent medication treatments (polypharmacy), and antidepressant
      treatment with serotonin reuptake inhibitors (SRIs). Inpatient youths were
      consistently prescribed more psychotropic medications and diagnosed more
      frequently with major depressive disorder than outpatients. Medications typically
      used to first treat mood disorders became the predominant medication prescribed
      for both outpatients and inpatients by child psychiatrists in 1994, leading to a
      proportional decline in prescribed stimulant treatment. The shift from tricyclic
      antidepressants to SRI antidepressants in the 1990s by child psychiatrists
      matches the same recent practice shift by adult psychiatrists. Likewise, the
      increased prescription of drugs to treat mood disorders and the increased rate of
      polypharmacy notable of late among child psychiatrists now also mirrors adult
      psychiatry practice. Wide geographic variations in neuroleptic and antidepressant
      medication patterns were noted, even among facilities in the same metropolitan
      region. After psychiatric hospitalization, most youths who continued treatment at
      a CMHC outpatient clinic discontinued their inpatient medications within 3
      months; the sole exception were children who had been placed on psychostimulants.

PMID- 9542699
TI  - Pediatric pharmacoepidemiology: clinical applications and research priorities in
      children's mental health.

PMID- 9542698
TI  - Prescribing practices of inpatient child psychiatrists under three auspices of
      care.
AB  - To study prescribing practices of inpatient child psychiatrists under 3 auspices
      of care, 137 medicated patients were compared to 122 nonmedicated patients at a
      state hospital, a private hospital and a county-university hospital in New York
      during 1991. Overall, 79% of state, 76% of private, and 68% of county-university
      hospital patients received at least one dose of psychotropic medication, with the
      state versus county-university comparison significant (p < 0.05). Significantly
      more medicated patients at the private hospital (80%) than at the state or county
      university hospitals (each 26%) received antidepressants (p's < 0.001).
      Significantly more county-university (74%) than private (35%) patients received
      antipsychotic medications, but the proportion of nonpsychotic patients receiving
      antipsychotic medication was statistically similar across the three hospitals. In
      nonpsychotic patients, antipsychotic agents were used to treat aggressive
      behavior. Patients 12 years of age or younger received more stimulants, and
      patients 13 years of age or older received more lithium (p's < 0.01). In a
      clinical review of medical charts of medicated patients from the 3 auspices of
      care, approximately 90% of the medication-treated patients were treated at an
      acceptable dose level and with an acceptable rationale based on symptom or
      diagnosis. These and other findings and other suggest that children in state
      hospitals are not over-medicated in comparison to children in private hospitals
      or university-county hospitals, and that prescribing practices among the three
      hospitals, despite their different funding sources, are comparable.

PMID- 9542700
TI  - Determinants of cancer screening frequency: the example of screening for cervical
      cancer.
AB  - BACKGROUND: Cancer screening frequency should be based on the rate of progression
      of the disease and the sensitivity of the screening test. A common misconception
      is that a person's risk of getting the disease determines how often they should
      be screened. METHODS: We describe algebraically the theoretical interaction of
      disease progression rate and screening test sensitivity determining the portion
      of invasive cancers prevented by screening. After discussing the assumptions and
      limitations of the model, we apply this model to the example of screening for
      cervical cancer. Actual data from large screening programs assembled by the
      International Agency for Research on Cancer (IARC) are used to test the
      assumptions of the model. RESULTS: A simple formula can express the relation
      between disease progression rate, sensitivity of the screening test, screening
      frequency, and screening error. Disease prevalence does not figure in this
      equation. The IARC data suggest that, at least for cervical cancer, as screening
      frequency increases, incremental sensitivity of the test decreases or remaining
      undetected cases progress more rapidly so that anticipated benefits from more
      frequent screening are not realized. CONCLUSIONS: Rate of disease progression and
      sensitivity of the screening test are the proper determinants of cancer screening
      frequency. Because these factors can vary depending on screening frequency,
      however, the optimal screening interval for a particular cancer must be
      determined by clinical trials.

PMID- 9542702
TI  - Frequent users of rural primary care: comparisons with randomly selected users.
AB  - BACKGROUND: Frequent users of primary care have not been adequately
      characterized. The unique characteristics of this population was sought--why they
      come so often, what their care costs, and whether psychosocial factors play a
      role in their high utilization of health care. METHODS: The billing system of a
      rural primary care clinic was used to find the frequency of visits for all
      patients attending the clinic for the previous 12 months. The 211 most frequent
      visitors were selected. A comparison group of 250 patients was drawn from the
      billing records using a random number generator. Charts were reviewed to compare
      diagnoses (by frequency), number of procedures, amount billed for care, amount
      received from those billings, number of psychotropic medications prescribed, and
      response to medication. A subgroup of each group was interviewed to confirm chart
      review findings and to inquire about personal reasons for coming to the clinic.
      RESULTS: Compared with patients who were random users, patients who were frequent
      users were more likely to come from the younger and older age groups, they
      averaged significantly more emergency department visits and visits to other
      specialists (P < 0.0001), and they had more mental health problems diagnosed (P <
      0.01). Significantly more frequent users were insured by Medicaid and fewer were
      insured by Medicare. They had more detailed office visits and more laboratory
      tests. They received twice as much psychotherapy and had a higher percentage of
      problem-focused office visits. Chart audits and interviews of selected patients
      revealed that many nonmedical reasons were related to visits in addition to
      psychosocial stressors. CONCLUSIONS: Nonmedical factors are important among the
      most frequent users of a primary care clinic. Proposals to improve care for
      frequent users should consider the psychosocial needs of this population.

PMID- 9542701
TI  - Computerized prompts for cancer screening in a community health center.
AB  - BACKGROUND: We describe the implementation and subsequent use of a computerized
      health maintenance tracking system in a large, urban, North Carolina community
      health center (Lincoln Community Health Center) as part of a larger study
      designed to increase rates of mammography, Papanicolaou tests, and smoking
      cessation in low-income African-Americans. METHODS: Clinicians from the Lincoln
      Community Health Center were involved in the design and implementation of the
      computer system. At each office visit, clinicians received a computerized
      encounter form indicating needed screening tests, counseling, and immunizations
      for each randomly selected study patient (n = 1318). RESULTS: Initial clinician
      compliance rates with filling out the form were 95 percent (mammography), 82
      percent (Papanicolaou test), 77 percent (clinician breast examination), and 55
      percent (smoking cessation). Cumulative compliance leveled off at 21 months to 65
      percent, 57 percent, 53 percent, and 38 percent, respectively, despite multiple
      reminder strategies. When surveyed, most clinicians thought it was a good
      reminder system but said they did not always complete the form because of time
      demands. Costs of adapting and implementing the system were $23,332.08 ($17.70
      per study). Per-patient costs would have been reduced further if more patients
      had been included in the project. CONCLUSIONS: State-of-the-art computer
      prompting systems can be useful in a community health center; however, even with
      prompting, clinicians still only addressed health maintenance with their patients
      about 50 percent of the time. Additional interventions will be needed,
      particularly in low-income populations, to meet the Healthy People 2000 goals in
      health promotion.

PMID- 9542703
TI  - Putting population-based care into practice: real option or rhetoric?
AB  - BACKGROUND: Efforts to improve care have focused on population-based approaches,
      though little practical information exists about implementation. METHODS: This
      report reviews relevant literature on teamwork in the context of a time-series
      evaluation of a demonstration project to reorganize care of a single panel of
      patients in a managed care setting. The proportion of the study panel achieving
      recommended levels for breast and colon cancer screening, warfarin control, and
      diabetic eye care was compared with the surrounding practice panels and the
      managed care population as a whole. Using unconditional logistic regression, we
      compared changes within populations between March 1993 and March 1995, and the
      rate of change between populations during the same period. RESULTS: A model of
      team care was successfully implemented. Colon (occult blood in the stool) and
      breast (mammography) screening increased more rapidly in the study population
      than in the surrounding practices or plan as a whole (P < 0.05 for all
      comparisons). There was no significant improvement in warfarin control or
      diabetic eye examinations, though absolute increases occurred. CONCLUSION: This
      work shows that a team approach to population-based care is a real option. Such
      an approach, however, will not generalize to other settings or all conditions,
      and its implementation involves some major challenges.

PMID- 9542704
TI  - The pharmacologic treatment of depression.
AB  - BACKGROUND: Family physicians often provide the first line of treatment for
      patients with depression. Many effective drugs are now available for the
      pharmacologic treatment of depression. METHODS: We searched Medline from 1991-96
      under the topics of depressive disorders/treatment and antidepressant
      medications. Other sources were found by back-referencing from these references
      and from pharmacology texts. RESULTS: Although antidepressants appear to be
      equally effective, selective serotonin reuptake inhibitors are frequently the
      drugs of choice because of their safety profile the less troublesome side
      effects. CONCLUSIONS: When prescribing antidepressant medications, the clinician
      must educate patients about potential side effects and about the amount of time
      that must be allowed for therapeutic efficacy. Drug interactions and concurrent
      medical conditions are important factors in the choice of an antidepressant.

PMID- 9542705
TI  - Polypharmacy: a case report and new protocol for management.
AB  - BACKGROUND: Polypharmacy is an important issue in primary care, yet few data are
      available concerning its prevalence, complications, and management in clinical
      medicine. The following case illustrates the clinical perils of polypharmacy and
      serves as a point for critical discussion. METHODS: MEDLINE was searched, using
      the key word "polypharmacy," from 1994 to the present. A case report of
      polypharmacy is described, and a novel protocol for the management of
      polypharmacy is proposed. RESULTS: Polypharmacy can lead to unnecessary expense,
      wasted time, and embarrassment on the part of the patient and confusion and
      mismanagement on the part of the physician. The literature reveals controversy
      surrounding the definition of polypharmacy and reflects the considerable
      morbidity and expense associated with polypharmacy. Finally, the SAIL protocol
      shows that physicians need to keep in mind simplicity, adverse effects,
      indications, and a precise list of all medications to manage appropriately a
      patient's drug regimen. CONCLUSIONS: Polypharmacy is associated with morbidity
      and iatrogenic complications. The SAIL protocol can be a useful tool in the
      management of this entity. More research needs to be done on the prevalence,
      complications, and management of polypharmacy.

PMID- 9542706
TI  - Thrombolysis in acute ischemic stroke.
AB  - The administration of rt-PA to patients with acute ischemic stroke can result in
      improved functional outcomes. The safe and effective use of rt-PA in routine
      medical practice requires that patients seek help early, have a well-defined
      onset of their symptoms, be carefully examined for contraindications to rt-PA,
      receive a CT scan and interpretation to exclude hemorrhage, and receive the drug
      within a 3-hour period (Table 5). Intravenous rt-PA is given in a dosage of 0.9
      mg/kg (up to a maximum of 90 mg) with 10 percent of the dose administered as a
      bolus followed by a 60-minute infusion within 3 hours of the onset of symptoms.
      If these conditions cannot be achieved, the drug should not be administered.
      Although most patients will not meet the criteria of the NINDS trial, rt-PA is an
      important advance in the treatment of acute ischemic stroke.

PMID- 9542707
TI  - Dog bites: hidden danger of fulminant sepsis.

PMID- 9542708
TI  - Acute toxicity from home-brewed gamma hydroxybutyrate.

PMID- 9542709
TI  - Individualized strategies in the era of combination antiretroviral therapy.

PMID- 9542710
TI  - Put to sleep.

PMID- 9542711
TI  - Polypharmacy: old bad habits.

PMID- 9542712
TI  - Man's best friend?

PMID- 9542713
TI  - Breath test and serologic testing for Helicobacter pylori.

PMID- 9542714
TI  - Management of Parkinson disease.

PMID- 9542715
TI  - Health problems of refugees.

PMID- 9542716
TI  - Training residents to care for handicapped patients.

PMID- 9542717
TI  - Localization of dopamine1A receptor mRNA in different vascular beds in rat: a
      nonradioactive in situ hybridization study.
AB  - In situ hybridization of a biotin-labeled specific dopamine1A (D1A) receptor gene
      oligonucleotide probe combined with computer-assisted image analyzer was used to
      directly visualize D1A receptor mRNA and quantify the relative mRNA levels in
      sections of rat aorta and pulmonary and caudal arteries. Positive D1A receptor
      mRNA signals were found in rat aorta and pulmonary arteries, while no specific
      signals could be detected in the caudal artery. D1A receptor mRNA was located
      mainly within the medial layer of aorta, with intimal distribution in the
      pulmonary artery. The density of D1A receptor mRNA in different vascular beds
      demonstrated heterogeneity. D1A receptor mRNA levels in the aorta were much
      higher than those in the pulmonary artery (p < 0.01). These results demonstrate
      the existence of D1A receptor mRNA in both aorta and pulmonary beds, although
      with different distribution and density. The results further support the
      heterogeneity of the D1A receptor in different vascular beds.

PMID- 9542718
TI  - Reversal of benzodiazepine inverse agonist FG 7142-induced anxiety syndrome by
      neurosteroids in mice.
AB  - We have previously shown that neurosteroids produce GABA-A receptor mediated
      antistress, anxiolytic and other behavioral effects in rodents. In the present
      study, the effects of neuroactive steroids on benzodiazepine receptor inverse
      agonist FG 7142-induced anxiogenesis were investigated using mirrored chamber and
      elevated plus-maze paradigms in mice. FG 7142 (5-20 mg/kg) not only produced a
      dose-dependent reduction in the duration of open arm exploration and the total
      number of open arm entries, but also increased the latency to enter the mirrored
      chamber, decreased the number of entries and total time spent in the chamber,
      indicative of anxiogenic-like effects. Neurosteroids allopregnanolone (0.5 and
      1.5 mg/kg) and pregnenolone sulfate (2 mg/kg) significantly reversed the FG 7142
      (10 mg/kg)-induced anxiogenic response in both the paradigms, without producing
      any neurotoxicity. While dehydroepiandrosterone sulfate (1 and 2 mg/kg) failed to
      influence the anxiogenic effects of FG 7142. The neuroactive steroid progesterone
      (1-10 mg/kg), and the mitochondrial diazepam binding inhibitor (DBI) receptor
      agonist 4'-chlordiazepam (0.5 and 1 mg/kg) dose-dependently blocked the FG 7142
      induced anxiogenesis in a flumazenil (2 mg/kg)-insensitive manner. The 4'
      chlordiazepam-induced reversal response was, however, prevented by pretreatment
      with PK11195 (2 mg/kg), a selective mitochondrial DBI receptor antagonist.
      Further, at the anxiolytic doses, these neurosteroids did not produce locomotor
      inhibition and ataxia. These data suggest that neurosteroids allopregnanolone,
      pregnenolone sulfate, progesterone and the mitochondrial DBI receptor agonist 4'
      chlordiazepam reverses the anxiogenic-like effects of benzodiazepine receptor
      inverse agonist FG 7142 in the mouse models of anxiety.

PMID- 9542719
TI  - Effect of nimodipine on the cognitive dysfunction induced by phenytoin and
      valproate in rats.
AB  - Anticonvulsant effects of phenytoin (PHT) and valproate (VPA) were studied alone
      and in combination with nimodipine (NMD) against maximal electroshock (MES)
      induced seizures in rats. PHT and VPA induce cognitive deficit in terms of long
      term memory loss. The effect of NMD on the cognitive deficit induced by PHT and
      VPA was studied through the step-through passive avoidance test (PAT). It was
      seen that there was a potentiation of antielectroshock effect of PHT and VPA when
      NMD at a dose of 4 mg/kg was combined with PHT or VPA. NMD reversed the long-term
      memory loss induced by PHT and VPA in the PAT.

PMID- 9542720
TI  - Alacepril, an angiotensin-converting enzyme inhibitor, prevents cerebral
      vasospasm in subarachnoid hemorrhage model in rats.
AB  - The effects of angiotensin-converting enzyme (ACE) inhibitors was investigated on
      the development of cerebral vasospasm and on the endothelium-dependent relaxation
      in the rat subarachnoid hemorrhage (SAH) model. Alacepril or enalapril was used
      as an ACE inhibitor with or without a thiol moiety in the structure. SAH rats or
      sham-operated rats were produced by the injection of homologous blood or
      artificial cerebrospinal fluid into the cisternal magna, respectively. In the SAH
      rat, cerebral vasospasm was observed at 24 h after blood injection. Acetylcholine
      (Ach)-induced relaxation in basilar arteries from SAH rats significantly
      decreased compared to that from sham-operated rats, although the relaxation
      induced by 3-morpholinosydnonimine, sodium nitroprusside or papaverine did not
      decrease. These results suggest that the endothelium cell function of basilar
      arteries in SAH rats is damaged. Alacepril prevented both the development of
      cerebral vasospasm and the suppression in the Ach-induced relaxation of basilar
      artery in SAH rats. However, enalapril did not prevent the suppression of Ach
      induced relaxation in SAH rats, despite the tendency to prevent cerebral
      vasospasm. Therefore, it is suggested that the preventive effect of alacepril on
      cerebral vasospasm could be based on its protective effect on endothelium
      dependent relaxation system.

PMID- 9542721
TI  - Further pharmacological study on Sho-seiryu-to as an antiallergic.
AB  - Examination was made of the pharmacological characteristics of Sho-seiryu-to, an
      antiallergic kampo medicine. Sho-seiryu-to suppressed histamine release from rat
      peritoneal mast cells, but failed to inhibit the binding of [3H]-mepyramine to
      histamine H1 receptors in guinea pig cerebral cortex and lung. Sho-seiryu-to had
      no effect on cutaneous reactions induced by serotonin, platelet-activating factor
      (PAF), leukotriene (LT) C4 or LTD4. Ketotifen prolonged electrically induced
      convulsions, while Sho-seiryu-to did not. Sho-seiryu-to did not affect salivation
      induced by pilocarpine. Sho-seiryu-to thus does not appear to inhibit histamine
      H1 receptors or inflammation induced by serotonin, PAF, LTC4 and LTD4, but
      suppresses mast cell activity. Sho-seiryu-to would thus have only a few side
      effects such as dry mouth and convulsions due mainly to the blockage of the
      action of muscarinic in salivary glands and histamine in the brain.

PMID- 9542722
TI  - Influence of food on glycemia, insulin, C-peptide and glucagon levels in diabetic
      patients treated with antidiabetic metformin at steady-state.
AB  - Seventeen diabetic patients (5 males and 12 females) treated with long-term
      metformin therapy received their morning dose after an overnight fast or after
      one of four types of breakfast: low protein, low fat, low carbohydrate or
      standard. Mean (+/- SD) and median areas under the serum concentration curves
      (AUC), maximum concentrations (Cmax) and time to reach the maximum concentrations
      (tmax) were calculated for the major biological parameters (glycemia, C-peptide,
      insulin and glucagon levels). None of the diets were bioequivalent to the fasting
      condition and only the low carbohydrate diet gave comparable results. A strong
      relationship was found between the carbohydrate intake (in g) and the AUC of the
      various markers except glucagon.

PMID- 9542723
TI  - Indirect pharmacodynamic response models do not require any parametric
      pharmacokinetic model to be fitted to effect-time data.
AB  - Indirect response models (IRM) represent one of the possible ways to explain and
      quantitatively describe a delayed pharmacodynamic effect at non-steady-state
      conditions. The standard way to get estimates of pharmacodynamic (PD) parameters
      of IRM consists of two steps. First, an appropriate parametric pharmacokinetic
      (PK) model (compartmental, polyexponential, etc.) is to be fitted to plasma
      concentration-time data, and then IRM is fitted to PD data having PD model as an
      input. In the present work it is demonstrated that a simple piecewise function
      which consists in interpolation lines connecting concentration-time points can be
      used as a universal nonparametric PK model thereby allowing to skip the first
      step. MS Excel spreadsheets implementing this PK model and four known versions of
      IRM are presented. The usefulness of the approach is demonstrated by fitting IRMs
      to simulated data as well as to real PK/PD data of warfarin and terbutaline.
      Estimates of IRM parameters obtained with the nonparametric PK model were close
      to that published in the literature.

PMID- 9542724
TI  - Free radicals and the pathobiology of brain dopamine systems.
AB  - Oxygen is an essential element for normal life. However, reactive oxygen species
      (ROS) can also participate in deleterious reactions that can affect lipid,
      protein, and nucleic acid. Normal physiological function thus depends on a
      balance between these ROS and the scavenging systems that aerobic organisms have
      developed over millennia. Tilting of that balance towards a pro-oxidant state
      might result from both endogenous and exogenous causes. In the present paper, we
      elaborate on the thesis that the neurodegenerative effects of two drugs, namely
      methamphetamine (METH, ICE) and methylenedioxymethamphetamine (MDMA, Ecstasy) are
      due to ROS overproduction in monoaminergic systems in the brain. We also discuss
      the role of oxygen-based species in 6-hydroxydopamine (6-OHDA)-induced
      nigrostriatal dopaminergic degeneration and in Parkinson's disease. Studies are
      underway to identify specific cellular and molecular mechanisms that are
      regulated by oxygen species. These studies promise to further clarify the role of
      oxidative stress in neurodegeneration and in plastic changes that occur during
      the administration of addictive agents that affect the brain.

PMID- 9542725
TI  - Serotonergic projections to the retina of rat and goldfish.
AB  - Serotonin amacrine cells have been described in the retina of vertebrates, except
      mouse and rat. Moreover, serotonin immunoreactive fibers have been reported in
      the optic nerve of rodents, frog and stingray. The purpose of this work was to
      study serotonin dorsal raphe nucleus projections to the retina, and to determine
      whether this pathway occurs in teleosts. The existence of specific connections
      was investigated in the rat and in the goldfish by the use of the neurotoxic
      substance 5,7-dihydroxytryptamine followed by monoamines determination in the
      retina by HPLC. The administration of 5,7-dihydroxytryptamine into the central or
      the lateral area of the rat dorsal raphe nucleus decreased serotonin levels in
      the raphe area and in the hippocampus, but only the bilateral injection into the
      dorsal raphe nucleus decreased it in the retina. In the goldfish, the injection
      of 5,7-dihydroxytryptamine into the optic tectum decreased serotonin
      concentration in situ and in the retina. The binding of [3H]paroxetine, a marker
      of serotonin transporter, was reduced in the retina of both species after the
      central treatment with the neurotoxic substance. In addition, the administration
      of the serotonin precursor 5-hydroxytryptophan into the optic tectum increased
      serotonin levels in the site of the injection and in the retina. The intraocular
      administration of 5,7-dihydroxytryptamine produced a big decrease in the content
      of retinal serotonin. This indoleamine and 5-hydroxyindoleacetic acid were
      detected in the optic nerves of rat and goldfish. The results indicate the
      existence of serotonergic retinopetal fibers in the rat and in the goldfish, a
      pathway that was not specifically demonstrated for the rat and was not previously
      proposed for the fish. The study of these serotonergic projections from the brain
      to the retina could be of interest in the understanding of the functional role of
      serotonin in the retina.

PMID- 9542726
TI  - Distribution of GABAA receptors in the limbic system of alcohol-preferring and
      non-preferring rats: in situ hybridisation histochemistry and receptor
      autoradiography.
AB  - The present study has employed quantitative receptor autoradiography and in situ
      hybridisation histochemistry to compare the expression of the mRNA encoding the
      alpha 1 and alpha 2 subunits of the GABAA receptor and the binding density of
      mature GABAA receptors in the limbic system of alcohol-preferring Fawn-Hooded
      rats (FH) with Wistar-Kyoto rats (WKY). Quantifiable levels of mRNA encoding the
      alpha 1 subunit were found in cortical regions, ventral pallidum, substantia
      nigra, horizontal limb of the diagonal band and the hippocampus of both rat
      strains. Interestingly, expression of the alpha 1 subunit mRNA was decreased by
      approximately 30% in the hippocampus of FH compared to WKY rats. Following a 28
      day period with free access to 10% ethanol, expression of the alpha 1 subunit
      transcript, was significantly increased in the piriform cortex and horizontal
      limb of the diagonal band, unaltered in the hippocampus but decreased in the
      substantia nigra of FH rats. Quantifiable levels of mRNA encoding the alpha 2
      subunit were found in nucleus accumbens, amygdala, cortical regions, lateral
      septal nucleus, hippocampus, medial habenula and ventral pallidum of both
      strains. Expression of the alpha 2 subunit mRNA was decreased by approximately
      35% in both the hippocampus and occipital cortex of FH compared to WKY rats.
      However, consumption of 10% ethanol in FH rats had no impact upon expression of
      the mRNA encoding the alpha 2 subunit in any region examined. Mature GABAA
      receptors were studied by autoradiography utilising the antagonist radioligand
      [3H]SR95531 and the agonist radioligand [3H]muscimol. Topographic binding
      throughout the limbic system of both strains was observed for both radioligands.
      Specifically, [3H]SR95531 binding was higher in the occipital cortex,
      hippocampus, lateral septal nucleus, superior colliculus and ventral pallidum of
      the FH rats compared to WKY rats; however, in the nucleus accumbens [3H]SR95531
      binding was lower in FH compared to WKY. Ethanol consumption had no measurable
      effect on the binding of [3H]SR95531 in FH rats. In the case of [3H]muscimol,
      binding was higher in the cortex, lateral septum and ventral pallidum of FH
      compared to WKY. Furthermore, ethanol consumption resulted in a 25-30% increase
      in [3H]muscimol binding in the lateral septum and striatum of FH rats. These data
      provide evidence for differential expression of GABAA receptor subunits in FH and
      WKY rats, and additionally indicate anatomically defined variations in GABAA
      receptor binding between the two rat strains.

PMID- 9542727
TI  - Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage
      independent Ca2+ channels.
AB  - Mechanisms underlying the 5-HT2A receptor induction of intracellular Ca2+
      mobilization and Ca2+ influx in type I astroglial cells in primary culture from
      newborn rat cerebral cortex were evaluated. The 5-HT-evoked Ca(2+)-transients,
      inhibited by the 5-HT2A antagonists ketanserin or 4-(4-fluorobenzoyl)-1-(4
      phenylbutyl) piperidine oxalate, consisted of an initial peak caused by inositol
      1,4,5-trisphosphate (IP3)-mediated Ca2+ release from internal stores, and a
      second sustained part which was due to Ca2+ transport over the plasma membrane.
      The responses were pertussis toxin-insensitive, suppressed by the phospholipase C
      inhibitor neomycin and were inhibited by the Ca(2+)-ATPase inhibitor
      thapsigargin. Furthermore, the responses were inhibited by the IP3 receptor
      antagonist heparin. When the second sustained part of the 5-HT-evoked response
      was studied, it was concluded that Ca2+ influx was not a result of opening of
      voltage operated calcium channels of either L, N or T-type. Instead it appeared
      that Ca2+ entered the cells through specialized voltage independent Ca2+ channels
      which were dependent of the IP3 production and subsequent Ca2+ release from
      internal stores. From this, we conclude that 5-HT opens Ca2+ channels in
      astrocytes which closely resemble depletion-operated Ca2+ channels (DOCCs).

PMID- 9542729
TI  - Effect of dantrolene on K(+)- and caffeine-induced dopamine release in rat
      striatum assessed by in vivo microdialysis.
AB  - Recently, dantrolene has been reported to affect the central nervous system in
      addition to peripheral targets such as skeletal muscle. We examined effects of
      dantrolene on K(+)- and caffeine-induced dopamine release in rat striatum using
      in vivo microdialysis. Perfusion with KCl via the dialysis probe for 20 min
      induced immediate increase in DA release. Either chelation of extracellular
      calcium or addition of dantrolene for 120 min preceded reapplication of 100 mM
      KCl for 20 min. Calcium chelation attenuated the increase in DA release induced
      by KCl. Application of dantrolene enhanced the KCl-induced increase in DA
      release, but this effect disappeared at 100 microM. Caffeine caused a dose
      dependent increase in dopamine release, independently of extracellular calcium.
      Treatment with 100 microM dantrolene for 120 min reduced the increase in DA
      release induced by caffeine. These findings that dantrolene modulates dopamine
      release in rat striatum indicate that conventionally administered dantrolene is
      likely to act on the central nervous system.

PMID- 9542728
TI  - Axonal transports of Boc-Gly-Arg-Arg-MCA hydrolysing enzyme in rat sciatic
      nerves.
AB  - Study on neural axon transport is a very useful method to find a neuron-specific
      protease. In the present study, the enzyme activity (release of 7-amino-4-methyl
      coumarin from t-butyloxycarbonyl-glycyl-L-arginyl-L-arginine-4-methylcoumaryl-7
      amide) was measured in the proximal, middle, and distal segments between 12 and
      120 h after double ligations of rat sciatic nerves to find precursor processing
      enzyme specific for pair of basic amino acid residue. The enzyme activity was
      significantly increased not only in the proximal but also in the distal segments
      12-120 h after the ligation, and the maximal enzyme activity was found in both
      segments at 72 h. The enzyme activity eluted by anion exchange chromatography of
      the proximal segment showed at least three peaks, and was slightly higher than
      the activity of the distal one. The activity in the middle segment was very low
      in comparison with the activity in the proximal and distal segments. These data
      indicate that some of the enzymes specific for pair of basic amino acid residue
      are transported by both anterograde and retrograde axonal flow, and may undergo a
      neuron-specific processing.

PMID- 9542730
TI  - Hypothalamic GABA-ergic activity and T-cell proliferation in aged mammal: effect
      of dietary protein.
AB  - Short-term supplementation of low protein diet (LPD) or high protein diet (HPD)
      to the aged (18 months old) rats did not change the hypothalamic GABAergic
      activity and immune response. Long-term supplementation of LPD on the other hand,
      enhanced hypothalamic GABAergic activity with an immunopotentiation by increasing
      the T-cell proliferating activity and peripheral blood lymphocyte count in the
      same age group of rats. Unlike LPD, HPD under long-term supplementation to the
      aged rats reduced the hypothalamic GABAergic activity with immunosuppression.
      These results thus suggest that (i) hypothalamic GABAergic activity is a
      regulatory index of immune response in aged mammals and (ii) long-term
      consumption of protein-poor or protein-rich diet may be an exogenous modulator of
      neuroimmune regulation in relation to central GABAergic activity and immune
      response.

PMID- 9542732
TI  - Differential regulation by pregnenolone sulfate of intracellular Ca2+ increase by
      amino acids in primary cultured rat cortical neurons.
AB  - We investigated the effects of pregnenolone sulfate (PS) on the [Ca2+]i increase
      induced by gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) using
      fluorescence imaging. PS inhibited the 50 microM GABA-induced increase in [Ca2+]i
      in a dose-dependent manner with an IC50 of 30 microM. The inhibitory effect of PS
      was apparent within 5 min and was in a non-competitive manner, suggesting that PS
      may act directly to the membrane level but indirectly to the GABA binding sites.
      Our previous study has already shown that the GABA-induced Ca2+ increase involves
      GABAA receptors and the similar pathway to a high K(+)-induced Ca2+ response
      (Takebayashi et al., 1996). Because 50 microM of PS could not inhibit a 25 mM
      K(+)-induced Ca2+ increase, it seems likely that the site of the inhibitory
      action of PS on the GABA-induced Ca2+ increase may be independent of the pathway
      of the high K(+)-induced Ca2+ response, but rather at GABAA receptor complex. In
      contrast, PS potentiated the 50 microM NMDA-induced increase in [Ca2+]i in a dose
      dependent manner. The magnitude of the NMDA response was approximately doubled in
      the presence of 100 microM of PS. However, PS did not affect the
      acetylcholine(Ach)-induced increase in [Ca2+]i. Furthermore, corticosterone had
      little effect on the GABA- and NMDA-induced Ca2+ increases, indicating that the
      alteration of the Ca2+ response is specific for PS. In conclusion, it is
      suggested that PS modulates differentially [Ca2+]i increase induced by GABA and
      NMDA.

PMID- 9542731
TI  - The neurochemical markers in cerebrospinal fluid to differentiate between aseptic
      and tuberculous meningitis.
AB  - In this study, the use of neurochemical markers in patients with aseptic and
      tuberculous meningitis has been investigated. The cerebrospinal fluid levels of
      amino acids, nitrite (a metabolite of nitric oxide), vitamin B12 and homocysteine
      were quantitated in both groups of patients. Among the amino acids, aspartic acid
      and glutamic acid both excitatory amino acid, GABA, glycine and tryptophan were
      all significantly increased in both patient groups whereas decreased level of
      taurine and increased level of phenylalanine were only found in patients with
      tuberculous meningitis. The levels of nitrite and its precursor arginine were
      significantly higher in patients with tuberculous meningitis whereas unchanged
      levels were found in patients with aseptic meningitis. A significantly increased
      homocysteine level and a decreased level of vitamin B12 were found only in
      patients with tuberculous meningitis whereas unchanged levels were found in
      patients with aseptic meningitis. This indicates that patients with tuberculous
      meningitis are particularly prone to vitamin B12 deficiency resulting into
      increased level of HC, and involvement of free radical showing the importance of
      these biological markers for promoting the possibility for the design of
      therapeutic approach.

PMID- 9542733
TI  - Brain benzodiazepine binding in aged rats.
AB  - Membrane [3H]flunitrazepam binding to central and peripheral benzodiazepine
      binding sites was studied in four brain areas (cerebellum, cortex, striatum and
      midbrain) of young (age 2-4 months) and aged (> 24 months) rats. A generalized
      reduction in the density of central binding sites (Bmax) was observed in all
      brain areas examined in aged rats. This reduction is irrelevant of the brain area
      and, according to literature, may correspond to cell loss and/or differential
      expression of mRNAs coding for the subunits of the GABA/benzodiazepine receptor
      complex during ageing. In the case of the peripheral binding sites, there was a
      decrease of Bmax in all brain areas with the exception of the cerebellum.
      However, the percent reduction of peripheral binding sites varied significantly
      among the different brain areas. These data suggest a differential effect of
      ageing on brain benzodiazepine binding which may reflect the special role for
      each brain area during ageing.

PMID- 9542734
TI  - Biological and clinical MRS at ultra-high field.
AB  - The advantages of performing spectroscopic studies at higher field strengths
      include increased SNR, improved spectral resolution for J-coupled resonances, and
      improvements in the selectivity of spectral editing schemes. By using pulse
      sequences that minimize the required echo time, refocus J-evolution, employ low
      peak B1 requiring pulses and take advantage of spectroscopic imaging methods,
      these advantages can also be utilized in clinical applications of spectroscopy at
      high field. In addition to the static measurements measurements of N-acetyl
      aspartate (NAA), creatine (CR) and choline (CH) which can be performed at 1.5 T,
      high resolution measurements of glutamate, glutamine, GABA and the incorporation
      of 13C labeled glucose into glutamate are possible with improved spatial and
      spectral resolution. These methods have been utilized in patients with seizure
      disorders and multiple sclerosis to identify, characterize and map the metabolic
      changes associated with these diseases and their treatment.

PMID- 9542735
TI  - Decoupling: theory and practice. I. Current methods and recent concepts.
AB  - Current methods for broadband heteronuclear decoupling are reviewed from a
      historical perspective. The principal concern is that decoupling should be
      effective over a wide range of chemical shifts without undue radiofrequency
      heating of the sample, particularly when human patients are involved. Continuous
      wave methods are the least efficient in this respect, followed by noise
      decoupling. Composite pulse schemes offer a more effective use of radiofrequency
      power, while adiabatic passage methods are the most efficient of all. Bi-level
      decoupling employs a low level of radiofrequency irradiation during the
      relaxation delay to maintain the nuclear Overhauser effect, with a higher level
      during signal acquisition in order to decouple over a wide frequency band. All
      decoupling sequences introduce cycling sidebands into the observed spectrum, and
      schemes are described to minimize the intensity of these artifacts. In part II,
      practical applications of decoupling methods are examined in the context of in
      vivo spectroscopy, where the improvements in sensitivity and resolution through
      broadband decoupling can be critical for solving clinical problems. Attention is
      focused on the regulatory limits on power deposition in these experiments. A
      tabulation of the existing work on decoupling in biological tissue is presented,
      mainly involving 31P and 13C spectroscopy in vivo or in vitro.

PMID- 9542736
TI  - Decoupling: theory and practice. II. State of the art: in vivo applications of
      decoupling.
AB  - Current methods for broadband heteronuclear decoupling are reviewed from a
      historical perspective. The principal concern is that decoupling should be
      effective over a wide range of chemical shifts without undue radiofrequency
      heating of the sample, particularly when human patients are involved. Continuous
      wave methods are the least efficient in this respect, followed by noise
      decoupling. Composite pulse schemes offer a more effective use of radiofrequency
      power, while adiabatic passage methods are the most efficient of all. Bi-level
      decoupling employs a low level of radiofrequency irradiation during the
      relaxation delay to maintain the nuclear Overhauser effect, with a higher level
      during signal acquisition in order to decouple over a wide frequency band. All
      decoupling sequences introduce cycling sidebands into the observed spectrum, and
      schemes are described to minimize the intensity of these artifacts. In part II,
      practical applications of decoupling methods are examined in the context of in
      vivo spectroscopy, where the improvements in sensitivity and resolution through
      broadband decoupling can be critical for solving clinical problems. Attention is
      focused on the regulatory limits on power deposition in these experiments. A
      tabulation of the existing work on decoupling in biological tissue is presented,
      mainly involving 31P and 13C spectroscopy in vivo or in vitro.

PMID- 9542737
TI  - Theory and application of array coils in MR spectroscopy.
AB  - The theory and application of array coils are reviewed in the context of phased
      array spectroscopy. The optimization of the signal-to-noise ratio from an array
      of coils is developed by considering the efficiency of a phased array transmit
      coil. This approach avoids the need to consider noise correlation, and should be
      useful in future considerations of transmit phased array coils for MR
      spectroscopy. Methods to characterize array coil performance, including fields
      and coupling are briefly summarized, along with methods to minimize the effects
      of mutual inductance. The signal-to-noise advantages of array coils over single
      coils are examined for both planar and cylindrical arrays. Numerical simulations
      of planar arrays of 2 x 2, 4 x 4 and 8 x 8 elements and constant overall
      dimension are compared to a single coil of the same size. The results demonstrate
      a significant improvement in sensitivity near the array coil. Although the
      benefits of the array decrease as a function of distance from the array, the
      array sensitivity never drops below that of a single coil with the same overall
      dimensions, or that of a single element of the array. Similar results are
      obtained for a sixteen element cylindrical array, which is compared to a standard
      quadrature birdcage coil using both computational methods and phantom
      measurements. The phased array techniques reviewed are demonstrated with proton
      spectroscopic images of the brain.

PMID- 9542739
TI  - Adiabatic pulses.
AB  - Adiabatic pulses are sometimes considered to be mysterious and exotic entities
      which are difficult to understand, complex to generate and impractical to
      implement. This work is an attempt to bring familiarity and to fulfill the
      preliminary needs of anyone interested in learning more about this subject. The
      response of magnetization to stimuli produced by adiabatic pulses is analyzed
      using vector representations in a frequency modulated rotating frame. The first
      section deals with basic principles of amplitude and frequency modulated pulses
      and a vector representation in a second rotating frame is used to explain how the
      adiabatic condition can be satisfied. The subsequent section explains the
      principles of offset independent adiabaticity. These principles are then used to
      design optimal functions for the amplitude, frequency, and magnetic field
      gradient modulations for adiabatic inversion pulses. The last section considers
      some practical aspects for those who want to develop methodologies involving
      adiabatic pulses.

PMID- 9542738
TI  - High spatial resolution and speed in MRSI.
AB  - The in vivo applications of magnetic resonance spectroscopic imaging (MRSI) have
      expanded significantly over the past 10 years and have reached the point where
      clinical trials are underway for a number of different diseases. One of the
      limiting factors in the widespread use of this technology has been the lack of
      widely available tools for obtaining data which are localized to sufficiently
      small tissue volumes to make an impact upon diagnosis and treatment planning.
      This is especially difficult within the timeframe of a clinical MR examination,
      which requires that both anatomic and metabolic data are acquired and processed.
      Recent advances in the hardware and software associated with clinical scanners
      have provided the potential for improvements in the spatial and time resolution
      of imaging and spectral data. The two areas which hold the most promise in terms
      of MRSI data are the use of phased array coils and the implementation of echo
      planar k-space sampling techniques. These could have immediate impact for 1H MRSI
      and may prove valuable for future applications of 31P MRSI.

PMID- 9542740
TI  - Metabolite-specific NMR spectroscopy in vivo.
AB  - An outline is presented of metabolite-specific in vivo NMR spectroscopy
      (particularly in brain). It reviews from a physical spectroscopist's perspective,
      the need for and the methods of observation of, individual metabolite resonances.

PMID- 9542741
TI  - Current awareness in NMR in biomedicine.

PMID- 9542742
TI  - Expression of hMSH2 and hMLH1 in colorectal carcinomas with microsatellite
      instability.
AB  - Microsatellite instability (MIN) due to defective mismatch repair (MMR) genes has
      been reported in a subset of sporadic colorectal carcinomas and in the majority
      of tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC)
      syndrome. Among the known MMR genes, hMSH2 and hMLH1 genes are known to be
      predominantly altered in HNPCC patients and MIN-positive tumors. In this study,
      we examined MIN and the protein expression pattern of the hMSH2 and hMLH1 by
      Western blot and immunohistochemistry from 32 sporadic colorectal carcinomas. MIN
      was observed in 6 (18%) colorectal carcinomas. Of the 6 MIN-positive tumors, one
      case showed no expression of either protein, 3 cases showed an absence of hMSH2
      protein expression, one case showed an absence of hMLH1 protein expression and
      one case showed no altered expression of either protein by immunohistochemistry.
      The decreased expression of the hMSH2 protein in a tumor compared to the normal
      mucosa was also observed in 5 of the 6 MIN-positive cases by Western blot
      analysis. All of the MIN-negative tumors showed expression of both proteins by
      immunohistochemistry. Thus most of the MIN-positive tumors appear to be directly
      related to the altered expression of these two genes and can be diagnosed by the
      examination of protein expression.

PMID- 9542743
TI  - Prognosticating tools in primary neuroendocrine (Merkel-cell) carcinomas of the
      skin: histopathological subdivision, DNA cytometry, cell proliferation analyses
      (Ki-67-immunoreactivity) and NCAM immunohistochemistry. A clinicopathological
      study in 25 patients.
AB  - Histopathologically, 18 of our patients had classical Merkel-cell carcinomas
      (MCC); seven had neuroendocrine (NE) carcinomas with features different from MCC,
      here called "aberrant MCC". These patients showed a progressive neoplastic
      disease with a fatal outcome in four of them. The cytometric DNA distribution
      pattern of the tumor cell nuclei of all the aberrant MCCs was found to be of the
      aneuploid type. By contrast, the neoplastic disease of the majority of patients
      with classical MCC ran a milder course; a fatal outcome occurred in only one of
      them. Here, the DNA ploidy pattern was of the euploid (diploid or tetraploid)
      type in eight cases and of the aneuploid type in another eight. Our recently
      described "proliferation cell index" (PCI), based on nuclear immunoreactivity
      (IR) with the proliferation "marker" antigen Ki-67, was significantly lower in
      those five MCCs of the classical "DNA-diploid" type than in the seven "DNA
      aneuploid" ones. These five patients presented a mild neoplastic disease; only
      one had a local recurrence and none had metastases. Otherwise, neither the PCI
      values nor the NCAM IR of the MCC cells were found to be of any prognostic
      significance.

PMID- 9542744
TI  - Oncogene expression in tumour cells of pediatric Hodgkin's disease in Argentina-
      correlation with Epstein Barr virus presence.
AB  - A new category of oncogenes regulating apoptosis, p53 and bcl-2, and the Epstein
      Barr virus (EBV) latent membrane protein-1 (LMP-1) have been related to Hodgkin's
      disease (HD) pathogenesis. We attempt to determine p53, mdm2, p21waf-1, bcl-2 and
      LMP-1 immunohistochemical expression in tissue sections from formalin-fixed,
      paraffin-embedded lymph node biopsies of pediatric HD. P53 was detected in the
      nucleus of Reed Sternberg cells and their variants (H-RS) in 68% of the HD cases.
      However, there was no statistically significant association with either clinical
      stages or with histological subtypes. P21waf-1, an indirect marker of p53
      functional status, showed nuclear labelling of H-RS in all the studied cases.
      MDM2 co-expressed with p53 in 62% of the cases, suggesting that both proteins
      regulate one another, in HD by a self regulatory loop. Bcl-2 cytoplasmatic
      expression in H-RS was demonstrated in 65% of the cases. There was co-expression
      of bcl-2 and p53 in 51%, but it failed to correlate with a poor prognosis. LMP-1
      labelling was shown in 51% of the cases, disclosing a statistically significant
      association with the under 6-year group (p = 0.005, Fisher's exact test). Since
      LMP-1 induces the expression of bcl-2 in vitro, the relation of both proteins was
      analysed and found to co-express in 15/37 cases, with a statistically significant
      association only in the under 6-year group (p = 0.001, Fisher's exact test).
      Abnormal accumulation of these oncoproteins in tumour cells could play a role in
      the pathogenesis of a subset of pediatric HD.

PMID- 9542745
TI  - The value of PCNA and AgNOR staining in endoscopic biopsies of gastric mucosa.
AB  - The aim of the present study was to examine the usefulness of the quantification
      of PC10-positive-cells and of Argyrophilic Nucleolar Organizer Regions (AgNORs)
      in gastric biopsies for the identification of gastric mucosal proliferative
      lesions. Fifty seven paraffin-embedded endoscopic biopsies were classified into
      four histologic groups: normal, inflammatory, dysplastic and neoplastic mucosa.
      The percentage of PC10-positive cells was determined by immunohistochemistry. The
      AgNOR parameters determined included the total number of all identifiable silver
      precipitations in the nucleus, the mean number of silver precipitations per
      cluster, and the presence of morphologically heterogenous silver precipitations.
      Group comparisons were performed using the Kruskall Wallis and Dunn non
      parametric tests with a significance level of 5%. A discriminant analysis
      (followed by the jack-knife procedure) was performed using the three AgNOR
      parameters plus the percentage of PCNA-positive cells as the independent
      variables and histological groups as the dependent variable. All three AgNOR
      parameters, as well as the percentage of PCNA-stained nuclei, showed their
      highest values in the carcinoma group. However, no good differentiation among the
      four histologic groups was obtained using only one of these parameters, since
      there was always considerable overlap among them. By combining all the parameters
      in a linear discriminant analysis, we obtained a correct classification in 48 out
      of 57 cases. Within the classification errors there was only one false positive
      carcinoma, which was in fact a dysplasia and only one false negative carcinoma
      erroneously classified as dysplasia. The number of cells with heterogenous AgNORs
      was the most important parameter for the discriminant analysis. No correlation
      between PCNA values and the AgNOR parameters could be found, thus indicating that
      they do not represent the same phenomenon in the cell cycle. We concluded that
      the use of a combination of various proliferation parameters in a linear
      discriminant analysis may be helpful for differentiating gastric mucosal lesions.
      The peculiar AgNOR morphology is an important variable which should be taken in
      consideration in quantitative studies. PCNA and AgNORs seem to represent
      different physiological phenomena in the cell cycle.

PMID- 9542746
TI  - Development of osteoarthritis in the knee joints of Wistar rats after strenuous
      running exercise in a running wheel by intracranial self-stimulation.
AB  - The influence of excessive running load on the development of knee osteoarthritis
      (OA) was investigated in male Wistar rats. Running exercises were performed in a
      running wheel using intracranial self-stimulation to motivate Wistar rats to run
      daily distances of 500 m at 5 days/week. Hereby, ten rats ran a distance of 15 km
      within three weeks while a further ten rats run a total of 30 km within six
      weeks. Thirteen Wistar rats without running exercises served as controls.
      Complete knee joint sections of all rats were evaluated histologically using
      MANKINs grading system with categorization of the findings into non, mild
      moderate, and severe osteoarthritis. In addition, immunoreactivity of the
      chondrocytes to MMP-3 as an important cartilage degrading enzyme in OA was
      assessed by immunostaining with monoclonal MMP-3 IgG antibodies. Histological
      assessment of the knee joint sections revealed a significant increase in
      osteoarthritic changes with higher running load. While in rats with 15 km running
      all but two knee joints showed mild OA, moderate OA was the predominant finding
      in rats with 30 km running. In contrast, no OA was found in the controls.
      Immunostaining for MMP-3 revealed a significant increase in immunoreactivity of
      the chondrocytes to MMP-3 with higher running load, indicating a running load
      depending production of this cartilage-degrading enzyme in the course of
      increasing OA. Compared to 47.4% immunoreactive chondrocytes to MMP-3 in the
      controls, this ratio rose to 70.4% in rats with 15 km running and even up to
      89.9% in rats with 30 km running. In conclusion, in Wistar rats, excessive
      running load leads to marked, running distance-depending osteoarthritic changes
      which are caused, at least in part, by an increase in MMP-3 production rising
      with greater running distance. Within this exercise model of OA, intracranial
      self-stimulation is an effective method to motivate Wistar rats to extremely
      excessive running in a running wheel. This model offers a wide range of further
      approaches to studying different processes of the development of OA.

PMID- 9542747
TI  - Multilocular cystic epithelioid leiomyoma of the uterus with focal lymphangioma
      like pattern: report of a case with immunohistochemical study.
AB  - We report a rare case of epithelioid leiomyoma of the uterus presenting as a
      multilocular cystic mass containing clear fluid. The histologic basis of cysts
      was the diffuse intratumoral cystic degeneration. Histologically, the presence of
      numerous cystic cavities of variable size raised the possibility that vascular
      abnormalities, such as hemangioma, lymphangioma, and diffuse cavernous
      angiomatosis, could be associated with epithelioid leiomyoma. An
      immunohistochemical study using endothelial cell and basement membrane markers,
      was helpful in excluding the vascular nature of the cystic cavities and revealed
      an unexpected focal lymphangioma-like pattern as a peculiar component of tumor.

PMID- 9542748
TI  - Angiomyxoma of the umbilical cord in one twin with cystic degeneration of
      Wharton's jelly. A case report.
AB  - We report the prenatal diagnosis of an angiomyxoma of the umbilical cord in a
      female fetus of a dizygotic twin pregnancy. The pregnant woman was hospitalized
      at 18 weeks for exclusion of a suspected exomphalos. Using high-resolution
      ultrasound and color doppler, the umbilical tumor (8 x 5 x 4 cm) was suspected to
      be an angiomyxoma without malformations in the fetus. Neither chromosomal
      aberrations nor elevated alphafetoprotein were found after amniocentesis. Serial
      examinations showed an increase in the size of the cystic mass without
      deterioration of the fetal condition. Macroscopical and microscopical
      examinations of the tumor performed after delivery revealed an angiomyxoma with
      cystic degeneration of Wharton's jelly. Tumors of the umbilical cord are rare
      anomalies and should be considered when using prenatal ultrasound for detection
      of cystic lesions.

PMID- 9542749
TI  - Alveolar soft part sarcoma of the uterine corpus. Report of two cases and review
      of the literature.
AB  - Alveolar soft-part sarcoma (ASPS) is a rare tumor of uncertain histogenesis,
      mainly localized in the extremities and less frequently found in the head, neck
      and trunk. The present report describes two cases of ASPS localized in the
      uterus. In general, this entity is very rarely encountered in the female genital
      tract. Including the two cases presented here, 27 patients have been described in
      the literature. Whereas the prognosis for ASPS in soft tissues is usually poor
      (most of the patients died of lung metastases), those localized in the female
      genital tract are associated with a much better survival. This could be explained
      by the fact that their diameter seldom exceeds 5 cm, the size which is regarded
      as being the critical prognostic limit. Histologically, both tumors showed the
      same characteristics as known for ASPS in other localizations: organoid or nest
      like arrangement of tumor cells; rounded or polygonal cells with cytoplasm of
      varying density; thin-walled, sinusoidal vascular spaces between tumor cell
      nests. Immunohistochemically, we found positivity for desmin and, to a lesser
      extent, for vimentin. Cytokeratin was negative, which is important in
      differential diagnosis to other rare uterine neoplasias like clear cell
      (mesonephroid) adenocarcinomas or metastases.

PMID- 9542750
TI  - Physiologic doses of urocanic acid do not alter the allostimulatory function or
      the development of murine dendritic cells in vitro.
AB  - Exposure to UVB results in the isomerization of trans-urocanic acid (UCA),
      localized in the stratum corneum, to cis-UCA. Cis-UCA can mediate at least some
      of the immunosuppressive effects of UVB, though the mechanism of cis-UCA action
      remains incompletely defined. Alterations in Langerhans cells, and other
      dendritic antigen presenting cell populations in the skin, may contribute to the
      loss of skin immune function following UVB exposure. Hence, this study was
      designed to investigate whether cis-UCA directly can induce changes in the
      immunostimulatory capacity of dendritic cells (DC) and the development of DC from
      precursor cells. Murine DC were generated from C57BL/6 bone marrow (BM) using
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and were used as
      stimulator cells in mixed lymphocyte reactions (MLR) using BALB/c lymph node
      cells (LNC) as responders. The addition of cis- and trans-UCA at concentrations
      ranging from 0.1-500 micrograms/ml to the MLR did not affect proliferative
      responses. Cis- or trans-UCA (100 micrograms/ml) was added to GM-CSF stimulated
      mouse BM cells on day 0, day 3 or day 5 of culture, and the phenotype and allo
      stimulatory function of the DC were analysed on day 7. Treatment with cis- or
      trans-UCA did not affect the numbers or the viability of cells in the BM
      cultures. In addition, the expression on DC of Iab, CD11c or the costimulatory
      molecules ICAM-1, B7-1, B7-2 and CD40 was not altered by the addition of cis-UCA
      to BM cultures. The inability of cis-UCA to alter the development of DC in vitro
      was confirmed by analysing the functional capacity of DC in MLR. DC generated in
      the presence of cis-UCA were equally efficient in the induction of allo
      stimulation, when compared with control DC. These results suggest that cis-UCA
      does not exert its immunosuppressive activity through direct effects on DC. Such
      activity may be independent of DC, or alternatively, cis-UCA may influence DC
      function indirectly, through the induction of secondary mediators.

PMID- 9542751
TI  - Assessment of skin types, skin colours and cutaneous responses to ultraviolet
      radiation in an Asian population.
AB  - Ninety normal individuals were included in this study on skin types, skin colours
      and cutaneous responses to ultraviolet radiation. Skin types were recorded using
      Fitzpatrick's classification, skin colours were measured using the Minolta
      Chromameter CR-300, and cutaneous responses to UV radiation were measured in
      terms of minimal erythema dose (MED) to UVA, UVB and the immediate pigment
      darkening dose to UVA (IPDDA). Skin colour measurements were taken from the right
      cheek to represent facultative skin colours, and from the buttock to represent
      constitutive skin colours. The colours measured were expressed by the L x a x b
      colour space. Skin types and some colour parameters (L and b from covered parts
      of body) correlated fairly well with the minimal erythema doses (MED) to UVA and
      UVB. Skin colour measurements are more objective than skin type assessment and
      could be better markers of photosensitivity. However, there is still considerable
      overlap in MEDs for persons with different skin colours, and further studies of
      these parameters are warranted. Our MEDs are higher than other reports on similar
      skin types and skin colours. This could be due to differences in methodology,
      genetic make-up or acclimatization from chronic sun exposure. This illustrates
      the importance of local controls for each institution dealing with photosensitive
      disorders.

PMID- 9542753
TI  - Total body heliotherapy.
AB  - Sunlight has long been known to be beneficial for a variety of skin diseases.
      Patients with psoriasis and eczema frequently employ ambient heliotherapy to
      control their conditions. However, social norms do not permit a person to expose
      the entire body in public, thus placing severe restrictions on the utility of
      this modality for the treatment of generalized psoriasis, for example. Tan-Thru
      bathing suits, designed to attract those who wish to tan without an accentuated
      "tan line", are reported to absorb ultraviolet (UV) rays up to a maximum
      equivalent of a sun protection factor (SPF) 10 sunblock, thus offering
      approximately 89% protection while in use, according to their manufacturer. If
      so, this bathing suit may allow patients with UV-responsive skin dermatoses to
      achieve full body exposure in a socially acceptable manner. The objective of this
      study was to verify the SPF and to determine the actual transmittance to skin
      covered by a Tan-Thru bathing suit. Ten healthy adult subjects were recruited for
      this investigation. UVB minimal erythema dose (MED) was determined on unaffected
      gluteal or lower back skin, once with and once without the swimsuit on. Our
      results showed that the mean SPF afforded by the bathing suit was in fact 4.9
      (range 4.5-5.6). In conclusion, theoretically, the Tan-Thru bathing suits could
      allow enough UVB penetration under ambient conditions to be beneficial for
      patients with UVB responsive conditions.

PMID- 9542752
TI  - Phototoxic lysis of erythrocytes from humans is reduced after oral intake of
      ascorbic acid and d-alpha-tocopherol.
AB  - Ultraviolet (UV) radiation causes hemolysis of human erythrocytes in the presence
      of photosensitizers. This can be used as an in vitro model for evaluating
      photosensitizing properties of substances. Antioxidants such as ascorbic acid
      (vitamin C) and d-alpha-tocopherol (vitamin E) have been found to be
      photoprotective in such test systems. We assessed the effect of combined systemic
      intake of both ascorbic acid and d-alpha-tocopherol by human volunteers on
      phototoxic in vitro lysis of their erythrocytes. In a double-blind placebo
      controlled study, 10 subjects took daily 2 g ascorbic acid combined with 1000 IU
      d-alpha-tocopherol, and 10 took a placebo. Blood was taken before and after 7
      days of treatment, erythrocytes were prepared and then incubated with 10(-3)
      mol/l fenofibrate, a photosensitizer acting in the UVA and UVB region. The
      suspensions were exposed to radiation rich in UVA (up to 40 J/cm2 UVA) or to
      radiation rich in UVB (up to 1.6 J/cm2). Photohemolysis of the samples was
      calculated as a percentage of complete hemolysis. At the end of the treatment
      phase, in the placebo group photohemolysis was not significantly reduced compared
      with the initial values at all irradiation doses except for 1.6 J/cm2 UVB (96% vs
      79%; P < 0.01). In the group taking vitamins, photohemolysis was significantly
      reduced at nearly all UV doses, most impressively after moderate UVA irradiation
      (20 J/cm2 UVA: 86.5% vs 14.5%; P < 0.01). It is concluded that the results of the
      photohemolysis test are influenced by the antioxidative status of the cell donor
      and that ascorbic acid and d-alpha-tocopherol also may protect against phototoxic
      damage in vivo.

PMID- 9542754
TI  - Green light is effective and less painful than red light in photodynamic therapy
      of facial solar keratoses.
AB  - Photodynamic therapy (PDT) with topically applied delta-aminolevulinic acid (ALA)
      is increasingly employed to treat patients with multiple solar keratoses and
      superficial skin tumors. For these indications, ALA-PDT has been shown to be
      highly efficient. Treatment of multiple or extended lesions, however, is
      substantially hampered by the fact that ALA-PDT is associated with burning pain
      during the irradiation procedure. The standard irradiation devices commonly used
      for ALA-PDT emit red light around 630 nm. In the present half-side comparison
      study we have observed that ALA-PDT employing a green light irradiation device
      (543-548 nm) is equally effective, as compared with standard red light ALA-PDT.
      In contrast to red light ALA-PDT, however, green light ALA-PDT caused only little
      tingling and burning but no pain. These observations indicate that green light
      ALA-PDT is superior to standard ALA-PDT, because it is associated with less
      unwanted side effects.

PMID- 9542755
TI  - How well are sunscreen users protected?
AB  - Previous studies have shown that people often apply less sunscreen than the
      recommended amount of 2 mg/cm2. Our purpose in this study was to determine
      objectively how photoprotection varies with application thickness. The protection
      provided by differing quantities of sunscreens containing varying amounts of
      titanium dioxide was measured in vitro using excised human epidermis as the
      substrate. It was found that application thickness had a significant effect on
      the sun protection factor (SPF), with most users probably achieving a mean SPF of
      between 20-50% of that expected from the product label. Underprotection due to
      inadequate application, coupled with overexposure to the sun, might partially
      explain why sunscreen use has been reported to be a risk factor in melanoma.

PMID- 9542756
TI  - Clearance of UVB-induced erythema in patients with non-melanoma skin cancer.
AB  - We have examined the clearance of UVB-induced erythema in 10 non-melanoma skin
      cancer (NMSC) patients, comparing their responses to a control group. All
      participants were followed to resolution of erythema, as measured by a
      chromameter. The resultant response pattern was modelled in three phases, with
      comparison of the rates of decay in erythema carried out. Analysis of the rapid
      decay phase demonstrated a significantly slower rate of resolution of erythema in
      the NMSC group, compared with the controls. Further elucidation of the molecular
      and genetic mechanisms controlling this response may improve our understanding of
      UV-induced carcinogenesis.

PMID- 9542757
TI  - Time course of 8-methoxypsoralen-induced skin photosensitization in PUVA-bath
      photochemotherapy.
AB  - In recent years PUVA-bath photochemotherapy has been shown to be an effective
      treatment modality for several dermatoses. A limitation of PUVA-bath
      photochemotherapy has been the lack of guidelines for optimal performance,
      including the time course of photosensitization of the skin exposed to the 8
      methoxypsoralen (8-MOP) bath water solution. In the present study 12 healthy
      volunteers were exposed to a 20 min bath in 150 l of an 8-MOP water solution (0.5
      mg/l, 37 degrees C). Immediately, as well as 1, 2, 3 and 5 h after the 8-MOP
      bath, irradiation was performed with increasing doses of UVA (0.5, 1, 2, 3, 5
      J/cm2) on 2 cm2 test areas. The minimal phototoxic dose (MPD) was determined 72 h
      after the UVA exposure. In all volunteers, photosensitization was highest
      immediately after the bath, with a MPD significantly below 5 J/cm2 (0.5-2 J/cm2).
      One hour after the bath, erythema could be induced by 2 to 5 J/cm2 UVA. Two hours
      after the bath, erythema could be induced using irradiation of 5 J/cm2 only in
      two volunteers. Three and five hours after the 8-MOP bath, no erythema could be
      induced in any volunteer by UVA doses up to 5 J/cm2. Our results indicate that
      optimal bath-PUVA requires UVA irradiation immediately after the 8-MOP bath.
      Further, these results imply that no restrictions on further sun exposure are
      mandatory 3 h after the 8-MOP bath, thus allowing the patient to pursue normal
      life activities.

PMID- 9542758
TI  - The antimicrobial effect of narrow-band UVB (313 nm) and UVA1 (345-440 nm)
      radiation in vitro.
AB  - Two new UV lamps were investigated with respect to their antibacterial
      effectiveness in vitro. Propioni (n = 20 strains) and Micrococcaceae (n = 16
      strains) bacteria extracted from acne patients were applied to RCM and sheep
      blood agar plates and irradiated with a narrow-band UVB lamp (TL 100W/10R) at a
      wavelength of 313 nm and a UVA1 lamp (TL 01) at a wavelength of 345-440 nm. The
      precisely defined energy levels were, in the case of narrow-band UVB, 0.00, 0.30,
      0.50, 1.00, 2.00 and 3.00 J/cm2 and, in the case of UVA1, 0.00, 2.50, 5.00, 7.50,
      10.00 and 20.00 J/cm2. UVA1 inhibited neither the growth of Propioni nor
      Micrococcaceae bacteria. In contrast, the growth of Micrococcaceae was inhibited
      already at a dosage of 0.30 J/cm2 of narrow-band UVB (P < 0.05), highly
      significant from 0.50 J/cm2 (P < 0.01) and to a maximum of 2.2 powers of 10 at
      3.00 J/cm2 compared with non-radiated control plates. Propioni bacteria were
      significantly inhibited at the minimum dosage of 0.30 J/cm2 of narrow-band UVB (P
      < 0.01) and to a maximum of 2.8 powers of 10 at 3.00 J/cm2.

PMID- 9542759
TI  - Laboratory testing of UV transmission through fabrics may underestimate
      protection.
AB  - Laboratory testing of the ultraviolet protection factor (UPF) provided by fabrics
      normally utilizes a collimated source of UV radiation and either a broadband
      sensor or spectroradiometer to detect the radiation, both unattenuated and after
      passing through the fabric sample held in a flat tensionless state. We report the
      results of an in vivo study of UV transmission through various T-shirts at
      several sites on the trunk and arms of a life-size mannequin irradiated with
      diffuse radiation and using UV sensitive polymer films as the sensor. We found a
      variation in UPF by a factor of two or more at different anatomical sites for a
      given T-shirt, with lower UPFs seen at sites where the fabric is stretched; and
      found that at every site and for each T-shirt this in vivo UPF was higher than
      the conventional in vitro UPF determined using collimated radiation.

PMID- 9542760
TI  - In vitro spontaneous and UVB-induced lymphocyte apoptosis are not specific to
      SLE.
AB  - We studied in vitro spontaneous and ultraviolet light (UV)-induced lymphocyte
      apoptosis in patients with systemic lupus erythematosus (SLE, n = 11), cutaneous
      lupus erythematosus (CLE, n = 8), and other collagen diseases (n = 6), as well as
      normal individuals (n = 6). Apoptosis was confirmed by the presence of a 180 bp
      DNA ladder on gel electrophoresis. UVB-induced apoptosis was observed in 4 of 11
      patients with SLE (36.3%), 3 of 8 patients with CLE (37.5%) and 2 of 6 patients
      (33.3%) with other collagen diseases. There was no clinical correlation between
      clinical photosensitivity and UV-induced apoptosis. Similarly, spontaneous
      apoptosis was also found in lymphocytes from patients with diseases other than
      SLE. No apoptosis was found in normal subjects with or without UVB irradiation
      (25 mJ/cm2). These data suggest that UV-induced lymphocyte apoptosis may not be
      specific to SLE but may be common in collagen diseases.

PMID- 9542762
TI  - A Ph.D. in clinical science for physicians: one solution to the vanishing breed
      of the physician-scientist.

PMID- 9542761
TI  - Relationship between skin phototype and MED in Korean, brown skin.
AB  - The Fitzpatrick skin classification has been a useful method to categorize
      cutaneous sensitivity to ultraviolet radiation (UVR), although it was based
      originally on responses in white skin. Because the relevance of this phototype in
      brown skin is in question, we investigated skin phototypes of university students
      by a self-reporting questionnaire and measured their MEDs in Korean, brown skin.
      After studying our explanation of the definition of Fitzpatrick skin types, 707
      Korean university students answered the questionnaire. We then measured UVB MEDs
      in 156 randomly selected male students. The order of frequency of skin type was
      type III (55.0%), IV (29.0%), and V (12.3%) by the questionnaire, with the sun
      sensitive categories (types I and II) reported only for 3.7%. There was no
      significant difference in MEDs between types IV and V, and the mean MED of each
      skin type did not show a monotonic increase with increasing skin type. Subjects
      with MEDs of 70-90 mJ/cm2 (corresponding to the MED of skin type V, as proposed
      by Pathak & Fitzpatrick) represented about half or more of the subjects in all
      categories, even types II and III. Subjects with MEDs lower than 60 mJ/cm2 were
      more prevalent in types II and III compared with types IV and V. We suggest that
      there is at best a weak relationship between the skin types, by the Fitzpatrick
      method, and MEDs in Korean, brown skin.

PMID- 9542763
TI  - The need for basic science research education in the medical school curriculum.

PMID- 9542764
TI  - The need for clinical research education in the medical school curriculum.

PMID- 9542765
TI  - Hepatitis B and C viruses: molecular identification and targeted antiviral
      therapies.
AB  - Four agents are in clinical development for the treatment of chronic hepatitis B
      infection. These nucleoside analogs are incorporated into the growing DNA chain
      and terminate replication. Lamivudine, a cytadine analog that inhibits the
      synthesis of negative strand DNA from pre-genomic RNA, predictably inhibits
      replication and improves liver enzymes and histology in infected individuals.
      Following cessation of treatment, relapse is common, and genetic causes of viral
      resistance have been described. Other drugs for HBV infection include
      famciclovir, a guanosine analog that has also shown to suppress replication in
      immunocompetent as well as in immunocompromised patients; lobucavir, a guanosine
      analog; and adevfovir, an adenine nucleotide analog. The future of drug therapy
      against HBV likely includes combination agents with one or more
      nucleoside/nucleotide analogs and immune stimulants, such as interferon, or
      therapeutic vaccines. Recent advances in the treatment of HCV have been less
      impressive. An effective vaccine is greatly needed yet development in the near
      future is unlikely. Recommendations for therapy of chronic HCV have been proposed
      following the National Institutes of Health Consensus Conference. Interferon
      alpha is advised in patients with elevated serum alanine aminotransferases and
      liver histology demonstrating active hepatitis, regardless of level of
      pretreatment viremia or infecting genotype. Therapy should be continued for three
      months, at which time response should be assessed. If a biochemical and/or
      virological response has been achieved, treatment should be continued for a year.
      Trials are underway to evaluate interferon in combination with ribavirin. Recent
      identification of the crystalline structure of the HCV NS3 protease promises
      development of effective inhibitors of this critical viral enzyme.

PMID- 9542766
TI  - The genetic basis of systemic lupus erythematosus.
AB  - Although cumulative evidence suggests that a genetic predisposition plays a major
      role in the development of systemic lupus erythematosus (SLE), the susceptibility
      genes are mostly unknown. The difficulty in identifying susceptibility genes is
      due in part to the inherent nature of this polygenic complex disease and the
      diverse genetic backgrounds of human populations. Murine SLE models that have
      homogenous genetic backgrounds are less complex for genetic dissection. Genome
      wide linkage studies of murine SLE have mapped the position of a number of
      susceptibility loci. Recently, several of these major murine loci have been shown
      to link to different clinical and laboratory features of lupus-like phenotypes.
      In addition, evidence for additional genetic contributions via interaction
      between murine loci has been reported. In human SLE, many polymorphic genes
      (which have potential roles in SLE, as suggested by their known functions) have
      been associated with SLE or SLE subsets by population-based case-control or
      within-case studies. Because more compelling genetic evidence includes linkage
      analysis, our group has used the identified murine susceptibility loci as a guide
      and conducted linkage analysis of genetic markers located within a specific,
      possibly syntenic human chromosomal region. Evidence for linkage of a chromosome
      1q41-42 region was observed in SLE-affected sibling pairs from multiple ethnic
      groups. This article summarizes recent developments and outlines possible future
      directions in delineating the genetic basis of SLE.

PMID- 9542767
TI  - Modulation of cytokine function by heparan sulfate proteoglycans: sophisticated
      models for the regulation of cellular responses to cytokines.
AB  - Cytokines are diffusible, soluble factors with pleiotropic actions. The ability
      of some cytokines to blind to and be immobilized by heparan sulfate proteoglycan
      (HS-PG) on either the surface of cells or within the extracellular matrix
      accentuates their action by 1) promoting the accumulation of cytokines at high
      concentrations in the appropriate location to encounter their target cells; 2)
      activating cytokines by inducing conformational changes in the bound cytokine; 3)
      promoting conformation-dependent association or polymerization of cytokines and
      their cell-surface receptors and facilitating the assembly of the appropriate
      molecular complex to initiate signal transduction; and 4) protecting cytokines
      from both chemical and physiological degradation. Furthermore, many interactions
      between HS-PG and cytokines are highly specific. Thus, variations in the HS-PG,
      core protein, or carbohydrate sequences that are seen at different sites or that
      occur with inflammation will determine which cytokines bind to a particular HS
      PG, providing multiple options for cytokine binding and regulation. HS-PG
      therefore plays a pivotal role in regulating the function of the large number of
      heparin-binding cytokines. The involvement of HS-PG in promoting paracrine,
      autocrine, juxtacrine, and matricrine functions provides a powerful and
      sophisticated model for regulating cytokine-mediated cellular interactions. These
      functions of HS-PG have direct relevance for the control of cell growth as well
      as for the pathogenesis of leukocyte trafficking and inflammation, cell
      infiltration, and tumor metastasis. Therapies aimed at modulating HS-PG/cytokine
      binding may provide powerful tools for inhibiting unwanted cytokine effects in
      several disease processes.

PMID- 9542768
TI  - Dual-parameter model for prediction of type I diabetes mellitus.
AB  - The recent cloning and recombinant expression of novel islet autoantigens
      [glutamic acid decarboxylase (GAD) 65 and islet-cell autoantibody 512 (ICA512)]
      has made possible the determination of whether the quantitative expression of
      autoantibodies to these molecules is correlated with age of diabetes onset and
      rate of progression to diabetes, similar to insulin autoantibodies (IAAs). We
      measured autoantibodies reacting with GAD65 (GAD65AA), ICA512 (ICA512AA), and
      insulin in patients who recently had received a diagnosis of diabetes and in
      first-degree relatives prospectively identified and then followed because of the
      expression of high titers of ICA. Levels of IAAs (but not GAD65AA or ICA512AA)
      correlated inversely with age at diagnosis of diabetes and directly with time to
      diabetes onset among the ICA-positive relatives. In multiple linear regression
      models, the level of IAAs remained a significant predictor of the time to
      diabetes after allowing for first-phase insulin secretion. The unique and
      dramatic association of IAAs with progression to diabetes suggests that IAAs
      contribute directly to disease pathogenesis or that levels of IAAs are influenced
      uniquely by the process, leading--at different rates in different prediabetic
      individuals--to type I diabetes. In addition, the linear regression model
      described (involving two variables, first-phase insulin secretion and levels of
      IAAs) aids in the prediction of time to diabetes among ICA-positive relatives.

PMID- 9542769
TI  - Cell-specific induction of hsp72-mediated protection by glutamine against oxidant
      injury in IEC18 cells.
AB  - Glutamine is a major metabolic fuel and trophic agent for intestinal epithelial
      cells that can enhance intestinal epithelial cell survival against oxidant and
      thermal stress, possibly through the induction of heat shock protein 72 (hsp72).
      In this study, we examined the possibility of a direct causal relationship and
      tissue specificity of glutamine-induced hsp72. Glutamine treatment of intestinal
      (epithelial) IEC18 cells, but not HeLa (epidermoid) cells, induces the production
      of hsp72 in a concentration-dependent fashion, without affecting the expression
      of the constitutively expressed heat shock protein, hsc73. To determine the
      specific role that hsp72 induction by glutamine plays in resistance of IEC18
      cells to oxidant injury, stable transfected cells expressing an hsp72 antisense
      construct were established. Although thermal induction of hsp72 was blocked only
      partially by the antisense construct, glutamine induction of hsp72 was completely
      inhibited. This was associated with a loss of the protective effects of glutamine
      against oxidant-induced stress. Thus, glutamine specifically induces hsp72 in
      intestinal epithelial cells, which mediates cell protection against inflammation
      induced stress such as oxidants.

PMID- 9542771
TI  - Creatine supplementation does not improve physical performance in a 150 m race.
AB  - Creatine supplementation has been shown by several authors to improve physical
      performance in very high intensity, intermittent, exercises. The effect on
      performance, as well as in plasma creatine and lactate concentrations has been
      studied in a group of twelve sprinters of national class when running a distance
      of 150 m on two occasions, before and after creatine (or placebo) supplementation
      for the previous three days. The most important differences in the biochemical
      parameters analyzed have been in plasma creatinine concentration, which increased
      substantially both before and after the race in the group that had received a
      daily supplement of 25 grams of creatine monohydrate for the previous three days.
      Creatine supplementation, therefore, did not improve physical performance, in the
      conditions, when running a 150 m distance.

PMID- 9542770
TI  - An HMG-I protein from human endothelial cells apparently is secreted and impairs
      activation of Hageman factor (factor XII).
AB  - A highly purified protein from lysates of human umbilical vein endothelial cells
      (HUVECs) inhibited the activation of factor XII [Hageman factor (HF)] and removed
      factor XIIa from an activating surface, thus impairing HF-dependent coagulation
      and kinin-releasing activities. Two tryptic peptides from this protein had 100%
      identity with amino acids 31-44 and 89-101 of a nonhistone DNA-binding protein
      known as high-mobility group protein (HMG-I). In specific antibody experiments,
      the clot-inhibiting property in purified lysate protein from HUVECs was
      associated with HMG-I. The molecular weight of the protein that inhibited
      clotting was consistent with that predicted for HMG-I. Protein that inhibited
      contact activation and had antigenic properties of HMG-I and HUVEC lysate protein
      also was found in conditioned media from unchallenged cultured HUVECs. After
      HUVECs were incubated with 14C lysine, conditioned media contained
      immunoprecipitable radiolabeled protein with the same molecular weight as that
      recovered from cell lysates, suggesting that this high-mobility group protein
      (HMG-I) may be secreted. Purified factor XII antigens were displaced from a glass
      surface by HMG-I from lysates in proportion to the amount of HMG-I protein that
      was added. This HMG-I probably inhibits factor XII functions because its high
      positive charge favors competitive binding to an activating substance.

PMID- 9542772
TI  - Heterogeneous responsiveness of normolipemic women to n-3 long chain fatty acid
      supplementation. Changes in serum lipids and apoproteins.
AB  - The effect of 10 day-low dosage of n-3 long chain fatty acids (390 mg/day of EPA
      and 252 mg/day of DHA) on lipid and apolipoprotein (Apo) concentrations has been
      studied in nine normolipidaemic women aged 28.9 +/- 4.2 years. n-3 fatty acid
      supplementation did not significantly decrease total cholesterol and triglyceride
      levels but markedly decreased the Apo A1 and Apo B concentrations (12.7%, p <
      0.01 and 23.1%, p < 0.001, respectively), while the Apo A1/Apo B ratio
      significantly increased (14.8%, p < 0.02). In contrast to the individual
      variations found for triglycerides and cholesterol, Apo changes indicate a fairly
      homogeneous response to the fish oil supplement. In seven women Apo A1 decreased
      (> 10%), whereas Apo B decreased (> 10%) in all of them. The Apo A1/Apo B ratio
      increased (> 10%) in five of these nine women. Changes in Apo A-1 and Apo B did
      not significantly correlate with changes in serum lipids. These findings suggest
      that short-term supplementation with low amount of n-3 long chain fatty acids,
      EPA and DHA, influences the serum Apo content more than the lipid levels in
      normolipidaemic women.

PMID- 9542773
TI  - Downmodulation of HLA class I expression by dexamethasone in MCF-7 cell line.
AB  - Several reports have shown the importance of MHC class I antigens in enabling the
      host to regulate tumour growth in vivo. Glucocorticoid hormones have strong
      immunosuppressive effects and are known to be regulators of gene transcription.
      In this report the expression of Major Histocompatibility Complex (MHC) class I
      antigens in six breast carcinoma cell lines have been studied before and after
      treatment with the synthetic glucocorticoid dexamethasone. Hence, HLA class I
      expression in the MCF-7 cell line was down-regulated in the presence of
      dexamethasone. This down-modulation of expression appeared to be mediated by
      transcriptional mechanisms, as revealed by HLA-class I mRNA levels.

PMID- 9542774
TI  - c-fos expression in the rat hypothalamic paraventricular nucleus induced by LiCl:
      descending projections to the dorsal vagal motor nucleus.
AB  - Anorexia inducing lithium chloride is believed to involve descending projections
      from hypothalamus to preganglionic autonomic output neurons. A multiple-labelling
      technique has presently been used to analyze the anatomical projections of
      lithium chloride sensitive neurons in the hypothalamus. Immunolabelling of c-fos
      was performed to stain neurons activated after LiCl administration, while neurons
      projecting toward vagal parasympathetic preganglionic levels were identified by
      injection of diamidino yellow in the dorsal motor nucleus of the vagus. Perikarya
      of descending neurons were mainly observed in the ventral and lateral areas of
      the paraventricular hypothalamic nucleus. In contrast, lithium chloride activated
      neurons were observed mainly in the magnocellular division of the paraventricular
      nucleus and supraoptic nucleus. Double-labelled neurons were not observed. These
      data provide evidence that lithium chloride sensitive neurons in the
      paraventricular nucleus are clearly different from those descending toward
      preganglionic vagal outflow neurons.

PMID- 9542775
TI  - Effects of 3-hydroxybutyrate on the hypoxic and reoxygenated atria from fed and
      fasted rats.
AB  - When exposed to hypoxia, the isolated atria from fed rats released lactate into
      the medium and underwent a decline of the peak developed tension and pacemaker
      frequency. The atria from 24-h fasted rats showed a rise in the resting tension
      together with a greater decline of the pacemaker rate and a lower lactate output
      than those from fed rats. The exposure to 5 mM 3-hydroxybutyrate caused only a
      small and brief decline in the pacemaker rate in the fed rats atria indicating
      that ketone bodies are able to exert only a minor detrimental effect on the
      hypoxic atria. Since the lactate output remained unaffected, this effect cannot
      be ascribed to a lowering in the energy supply from anaerobic glycolysis. On the
      contrary, 3-hydroxybutyrate improved the post-hypoxic recovery of the peak
      tension in the atria from fasted rats. This finding may be reflecting an
      anaplerotic role of 3-hydroxybutyrate, thus suggesting that in addition to
      glucose a second substrate is needed to meet the energy demand in the
      reoxygenated atria from fasted rats.

PMID- 9542776
TI  - Rate of muscle protein synthesis in rats fed raw and extruded pea diets.

PMID- 9542777
TI  - Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid
      arthritis.
AB  - Tetracyclines exert, independently of their antimicrobial activity, anti
      collagenolytic effects by inhibiting activities of human interstitial
      collagenases and by preventing the oxidative activation of latent pro
      collagenases. We tested the clinical response to a 3-month doxycycline in concert
      with collagenase activity in 12 rheumatoid arthritis (RA) patients. Patients
      received 150 mg/day of doxycycline for 3 months. Clinical assessments at zero,
      six and 12 weeks comprised classification of the functional class, joint score
      index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS)
      of pain, pain disability index, comprehensible psychopathological rating scale
      (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and
      Western blots. Significant reductions were seen in joint score index (P < 0.01),
      pain VAS (P < 0.05) and some CPRS parameters. Furthermore, collagenase activities
      measured from saliva by quantitative SDS-PAGE electrophoresis were significantly
      reduced during the 12-week intervention (P < 0.01). Western blots demonstrated
      intact 75-80 kDa enzyme protein (classic neutrophil collagenase), but also a
      newly discovered mesenchymal, less glycosylated 40-55 kDa MMP-8 subtype of
      fibroblast/chondrocytic origin. These results indicate that the documented
      favourable clinical response may in part be due to in vivo inhibition of classic
      neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline.
      This anti-collagenolytic doxycycline effects is mediated through inhibition of
      the enzyme activity and not through degradation of the enzyme, which may have
      contributed to the reportedly reduced tissue destruction, as has been seen in
      clinical studies concerning RA as well as reactive arthritis.

PMID- 9542778
TI  - Ankylosing spondylitis and infections of the female urogenital tract.
AB  - Thirty-two female patients with confirmed ankylosing spondylitis (AS) and 33
      women of similar age with pure ileitis terminalis Crohn were examined for
      genitourinary infection. Urethral syndrome was found in 15 out of 32 patients
      with AS: 11 of them had urethritis and 4 urethritis associated with vaginitis.
      Five women of the control group suffered from urethritis. In all cases with
      genitourinary infection, Chlamydia trachomatis was isolated. By comparing the AS
      patients (urogenital infection group and the non-infected group) with regard to
      other present clinical parameters, it was found, as expected, that the
      erythrocyte sedimentation rate in the 1st hour was significantly higher in the
      infected group. In addition, the infected patients had a significantly higher
      incidence of enthesopathy, involvement of the spinal column, and higher C
      reactive protein values (CRP > or = 5 mg/l). A family history of AS was equally
      present. Other clinical parameters, such as inflammatory involvement of the
      joints and HLA-B27 correlation, did not differ significantly between infected and
      non-infected patients.

PMID- 9542779
TI  - TNF-alpha induces the transcription factor Egr-1, pro-inflammatory cytokines and
      cell proliferation in human skin fibroblasts and synovial lining cells.
AB  - In rheumatoid arthritis (RA) cell proliferation and altered metalloproteinase
      expression of synovial lining cells are associated with increased levels of TNF
      alpha in the rheumatoid joint. We previously showed that synoviocytes of RA
      patients express high levels of the transcription factor Egr-1. Here we report
      that TNF-alpha is capable of inducing high Egr-1 mRNA levels in human skin
      fibroblasts and in synoviocytes from both, RA and reactive arthritis patients.
      Moreover, we observed in vitro a marked increase in fibroblast proliferation, a
      loss of growth inhibition by cell-to-cell contact with pannus-like cell growth
      and an altered cytokine expression pattern when synoviocytes were cultured in
      presence of TNF-alpha.

PMID- 9542780
TI  - The demographic and clinical spectrum of Arab versus Asian patients with
      ankylosing spondylitis in the UAE.
AB  - Ankylosing spondylitis is a rather uncommon condition in the UAE. Over a period
      of 10 years. 28 hospital-based patients diagnosed as having AS were
      retrospectively studied. They included 17 Arabs and 11 Asians. The onset of AS in
      most patients in this study was in adulthood (mean age at onset was 27.7 years in
      Arabs and 28.75 years in Asians). HLA B27 was positive in 56 and 81% in these two
      populations, respectively (P > 0.05). Analysis of these figures, however, along
      with previous relevant published data, could indicate that Arabs with AS are less
      likely to be B27-positive than Asians. Among the Arab patients there was not a
      single case from the local community, which could be attributed to the extremely
      low rate of B27 phenotype in their normal population. The interracial variations
      in the frequency of clinical features were statistically insignificant, therefore
      indicating some degree of similarity in the form and disease expression in both
      groups. AS is characterized as being predominantly axial in the majority of our
      patients. Extraspinal (oligo-poly) arthropathy involved mainly hips and knees,
      and there have been fewer extra-articular manifestations compared with other
      series published.

PMID- 9542781
TI  - Pharmacokinetic effects of conversion to a new formulation of cyclosporin A in
      rheumatoid arthritis patients.
AB  - In this study we aimed at evaluating the modifications in the pharmacokinetic
      profile of cyclosporin A (CyA) after conversion from standard formulation (CyA
      ST) to a new formulation (CyA-NF, Sandimmun Neoral) in patients with rheumatoid
      arthritis (RA). It was an open, crossover study that involved 15 RA patients who
      were on stabilized treatment with CyA-ST. The patient continued receiving CyA-ST
      (mean dose of 3.0 +/- 0.7 mg/kg per day) for 3 weeks and then converted 1:1 to
      CyA-NF for a further 3 weeks. CyA pharmacokinetics were established on day 1 (CyA
      ST evaluation) and +21 (CyA-NF evaluation). The results showed that the
      bioavailability of CyA-NF was greater than that of CyA-ST (AUC tau, bss: 3335 +/-
      1300 vs 2667 +/- 1155 ng.h/ml, P = 0.0073; AUC tau, bss ratio 1.26 +/- 0.40 vs
      1.0 as reference, P < 0.05), with higher and earlier peak blood concentrations
      (Cmax: 677 +/- 256 vs 475 +/- 213 ng/ml, P = 0.0329; tmax: 1.5 +/- 0.7 vs 2.6 +/-
      1.6 h, P = 0.0720). The pharmacokinetic profile of CyA-NF showed greater between
      patient reproducibility (lower CV% for all of the considered parameters). In
      conclusion, when using CyA-NF instead of CyA-ST, greater and more constant
      exposure to CyA should be expected.

PMID- 9542782
TI  - Antibiotic sensitivity and proticine typing of Proteus mirabilis strains
      associated with rheumatoid arthritis.
AB  - Urinary isolates of Proteus mirabilis, obtained from 49 RA patients and 44
      healthy controls, were tested for susceptibility to antibiotics by the disc
      diffusion method. In addition, P. mirabilis isolates were also tested for
      proticine production and sensitivity (p/s) typing by the inhibition of growth of
      each test isolate against 13 reference strains of P. mirabilis. The P. mirabilis
      isolates from both RA patients and healthy controls were highly susceptible to
      norfloxacin, ciprofloxacin and trimethoprim, but less to minocycline. The urine
      of RA patients contained fewer different types of P. mirabilis strains than those
      isolated from healthy controls. All of the strains found in the RA patients were
      proticine producers (P < 0.001), mostly of proticine 3 (P < 0.005). The presence
      of such strains provides evidence of a sub-clinical upper urinary tract infection
      with P. mirabilis in some RA patients. Therapeutic intervention in RA with
      relevant antibiotics requires evaluation.

PMID- 9542783
TI  - Diagnosis of idiopathic myositis: value of 99mtechnetium pyrophosphate muscle
      scintigraphy and magnetic resonance imaging in targeted muscle biopsy.
AB  - Our objective was to study the value of 99mtechnetium-pyrophosphate (99mTc-PYP)
      muscle scintigraphy and magnetic resonance imaging (MRI) in detecting areas of
      likely muscle inflammation and in increasing the rate of positive muscle biopsies
      in patients with suspected myositis. The results showed that in 13 out of 13
      patients with clinical and/or signs of inflammatory muscle disease, increased
      99mTc-PYP uptake was demonstrated at different muscle sites 3 h after isotope
      injection. Subsequent MRI of symmetric muscle areas with enhanced 99mTc-PYP
      uptake revealed signal patterns suggesting inflammation in all cases. Biopsy of
      these targeted muscles demonstrated characteristic histopathologic signs of
      muscle inflammation in 9 out of 13 patients. Four of these 9 patients had
      clinically atypical disease or did not show elevated creatine phosphokinase
      levels. Seven of these 9 patients had not been pretreated with corticosteroids.
      In 4 patients only muscle fiber atrophy and/or necrosis without cellular
      infiltrations was seen. These 4 patients had received either high doses of
      corticosteroids or low doses over longer periods of time before muscle biopsy. In
      conclusion, the combination of 99mTc-PYP muscle scintigraphy and MRI demonstrated
      muscle areas with maximum inflammatory signal patterns. Targeting of muscles by
      MRI only will probably yield reliable results of muscle biopsy in cases of
      clinically and serologically characteristic myositis. 99mTc-PYP muscle
      scintigraphy may provide useful initial information about localization of
      inflamed muscle tissue, especially in atypical disease. Treatment with
      corticosteroids prior to histologic diagnosis may abolish inflammatory
      infiltrations in affected muscle tissue.

PMID- 9542784
TI  - The New York High-Risk Project: attention, anhedonia and social outcome.
AB  - In the New York High-Risk Project we have followed two samples of subjects
      (Sample A and Sample B) at risk for schizophrenic or affective disorders and low
      risk controls from childhood to adulthood, in an attempt to identify early
      predictors of later psychopathology. We administered a large number of cognitive,
      psychometric and other types of measures to both samples as possible
      psychopathology predictors, including an index of attentional deviance assessed
      in childhood, the Physical Anhedonia Scale in adolescence, and three measures of
      social outcome in adulthood ('Suspicious Solitude', 'Social Insecurity', and
      'Lack of Empathy'), derived from the Personality Disorders Examination. In the
      analysis of the combined samples, parental diagnostic group, gender, attentional
      deviance in childhood, and physical anhedonia in adolescence were used to predict
      three measures of social outcome in adulthood. While only physical anhedonia was
      directly related to all three social outcome measures, with the strongest
      relationship to Suspicious Solitude, attention deviance successfully predicted
      two of the three outcomes. Subjects at risk for affective disorder did not show
      increased levels of attention deviance, physical anhedonia, or social
      dysfunction, relative to the normal control subjects. Attention deviance appears
      to be a key neurobiological indicator and physical anhedonia appears to be a
      potentiating factor mediating the relationship between risk for schizophrenia and
      later social dysfunction.

PMID- 9542785
TI  - The state of functioning of working memory in schizophrenia.
AB  - The functioning of working memory in schizophrenic patients according to
      Baddeley's model was examined in two complementary experiments. Experiment 1
      comprised 27 patients and their controls, matched in age and level of education.
      Of this pool, 20 pairs participated also in Experiment 2. Digit span, reading
      rate, and immediate serial recall assessed the functioning of the phonological
      loop. Corsi and pattern span tasks assessed the capacity of visuo-spatial memory.
      The central executive's ability to monitor two concurrent tasks was evaluated in
      a dual task paradigm, and its capacity to control action in a random generation
      task. A preliminary set of analyses showed that the patients' performances were
      reduced in all tasks explored, except in digit span. This initial pattern changed
      consistently after controlling for reading rate. While slow and fast reading
      patients were comparable in demographic and clinical criteria, slow reading
      patients showed impaired performance in all tasks, whereas fast reading patients
      exhibited reduced performance in visuo-spatial tasks and in the random generation
      task only. The state of functioning of working memory in schizophrenia appears,
      therefore, to vary consistently among the components of the model and is markedly
      impaired in slow reading patients. The implications of slowness are discussed.

PMID- 9542786
TI  - Memory impairment and schizophrenia: the role of processing speed.
AB  - A link between slowing of processing speed and cognitive disorders, including
      memory, has repeatedly been found in research on aging, and suggested in other
      cognitively impaired populations. We tested the hypothesis that a link between
      memory impairment and slowing of processing speed would also be observed in
      schizophrenia. Forty-four schizophrenic patients and 40 normal controls were
      administered a memory task involving free recall and recognition. Processing
      speed was assessed by the Digit Symbol Substitution Test. Working memory span was
      assessed as well. The measure of processing speed was consistently correlated
      with the various memory measures in patients, including efficiency of encoding.
      These correlations remained significant, or tended to be significant, when
      working memory span was partialled out. Memory deficits observed in schizophrenia
      may thus be partly accounted for by a slowing of processing speed. It is
      suggested that research on cognitive deficits in this and other mental diseases
      focus more on processing speed.

PMID- 9542787
TI  - Cognitive processing efficiency in schizophrenia: generalized vs domain specific
      deficits.
AB  - The issue of generalized vs specific cognitive deficits in schizophrenia was
      explored by examining reaction time data from 40 published studies with 196
      reaction time conditions. Using a regression-based approach, the proportional
      relationship between the response times of groups with schizophrenia was compared
      with those of age-matched, healthy comparison groups. Through this method, the
      extent to which deficits in processing efficiency are explained by a single
      factor, general processing speed, was compared with possible domain specific or
      task specific deficits. The results suggest that, overall, the data conforms well
      to a general linear slowing model which accounts for 87% of the variance in
      reaction time performance. Some additional variance, however, is accounted for by
      different degrees of linear slowing for three types of tasks: tasks involving
      selective attention/inhibition showed the most slowing (2.3-times slower for
      schizophrenia), followed by lexical tasks (1.8-times slower for schizophrenia),
      and finally, non-lexical tasks showed the least slowing (1.4-times slower for
      schizophrenia). This pattern is distinct from other groups showing generalized
      slowing, such as older adults, and suggests a unique pattern of information
      processing deficits in schizophrenia.

PMID- 9542788
TI  - Delusional disorder and eye tracking dysfunction: preliminary evidence of
      biological and clinical heterogeneity.
AB  - This study used eye tracking movement tests to examine the relationships between
      frontal field functions and clinical features. Smooth pursuit and voluntary
      saccadic eye movements were recorded and analyzed in 34 delusional disorder (DD)
      patients and in 40 normal subjects. The DD group differed significantly from the
      group of normal subjects in some eye tracking performances. As reported in our
      previous study (Gambini et al., 1993), DD patients showed abnormalities of
      voluntary saccadic eye movements. In this study, we also found abnormal smooth
      pursuit eye movements, indicating a cerebral dysfunction similar to those
      detected in schizophrenic patients. Moreover, normal smooth pursuit eye movement
      performance in DD patients was related to remitted depressive mood and probably
      to benefit from antipsychotic medications, thus supporting the idea of the
      biological and clinical heterogeneity of DD.

PMID- 9542789
TI  - Familial transmission of two independent saccadic abnormalities in schizophrenia.
AB  - Difficulties with inhibiting inappropriate responses, i.e. disinhibition, and
      problems with spatial memory are both presumed to be a part of the phenotypic
      expression of the genetic risk for schizophrenia. Schizophrenic probands are
      impaired on saccadic eye movement tasks which require (a) response inhibition to
      prepotent stimuli and (b) generation of an accurate response to a remembered or
      calculated spatial location, but it is unknown how these deficits are inherited.
      Sixteen schizophrenic probands, their 32 parents, and two normal control groups
      completed a delayed oculomotor response and an antisaccade task. The parents with
      a positive ancestral family history for chronic psychosis (n = 8) were presumed
      to be more likely than their family history-negative spouses to be genetic
      carriers for schizophrenia. Probands and their positive family history parents
      had more failures of response inhibition than did normal control groups. However,
      it was the probands and their negative family history spouses who demonstrated
      impaired accuracy of the remembered- or antisaccades. Disinhibition may be
      closely tied to a specific genetic risk for schizophrenia. However, a second
      familial factor related to the maintenance or manipulation of spatial information
      may also contribute to the genetic risk of the full clinical disorder.

PMID- 9542790
TI  - Multiple site evaluation of P50 suppression among schizophrenia and normal
      comparison subjects.
AB  - Normally, when two brief, non-startling auditory stimuli are presented 500 ms
      apart, with long (e.g., 10 s) interpair intervals, the positive potential
      occurring approx. 50 ms after the first stimulus (P50) is relatively large, and
      the P50 to the second stimulus is smaller. In schizophrenia patients, however,
      the P50 to the second stimulus is larger than normal. In this study, 36
      schizophrenia and 36 normal comparison subjects were tested in a two-click
      paradigm. Data were recorded from six electrode locations (F3, Fz, F4, C3, Cz,
      C4). The results support the hypothesis that schizophrenia patients have poor P50
      suppression that is not an artifact of differential P50 wave morphology or
      differences in the number of usable trials between groups. In addition, the
      vertex location alone (Cz) was equal to, if not better than, any combination of
      sites for differentiating between groups. These results support the use of the Cz
      site alone in most investigations of P50 suppression deficits among schizophrenia
      spectrum patients. Further work investigating the neuropathological correlates of
      poor P50 suppression among schizophrenia patients by recording from multiple
      electrode locations, however, could be helpful.

PMID- 9542791
TI  - MRI correlates of treatment response in first episode psychosis.
AB  - It is not known whether the magnitude of the structural brain abnormalities that
      underlie schizophrenia is a determinant of the extent to which patients respond
      to antipsychotic medication. This study was undertaken in order to explore this
      relationship. Twenty-six patients receiving treatment for a first episode of
      psychosis were involved in both a study measuring treatment response and a
      magnetic resonance imaging (MRI) study. In the treatment study, haloperidol dose
      was increased weekly beginning at 2 mg/day until patients showed evidence of a
      response or extrapyramidal symptoms. MRI scans were analyzed using a computerized
      volumetric approach to yield estimates of cerebrospinal fluid (CSF), gray-matter
      and white-matter volumes. Improvement in positive and negative symptoms after 1
      week of treatment was significantly correlated with cortical gray-matter volumes.
      Those patients who were maintained on 2 mg/day of haloperidol had greater
      cortical gray-matter volume than those who were treated with higher doses. The
      severity of structural brain abnormalities at the onset of psychosis may
      contribute to individual variation in response to antipsychotic medication. It
      remains to be determined whether the degree to which particular domains of
      symptomatology can improve is related to the severity of structural brain
      pathology in specific brain regions.

PMID- 9542792
TI  - Prolactin response to D-fenfluramine challenge test as a predictor of treatment
      response to haloperidol in acute schizophrenia.
AB  - D-fenfluramine has been identified as a highly selective serotonin (5-HT)
      releaser and re-uptake inhibitor. The objective of our study was to investigate
      prolactin response to D-fenfluramine challenge in non-medicated, first episode
      schizophrenics. We hypothesized that 5-HT reactivity can predict a response to
      the neuroleptic treatment. Twenty-three inpatients, 11 males and 12 females, at
      the Prague Psychiatric Center participated in the study. Inclusion criteria were:
      ICD-10 diagnosis of schizophrenia, first episode or duration of illness shorter
      than 36 months. D-fenfluramine challenge test was performed before 4 weeks of the
      haloperidol treatment. During the test, prolactin plasma levels were measured.
      The Brief Psychiatric Rating Scale (BPRS) was administered before and after the
      treatment. A statistically significant negative correlation was found between
      prolactin response to the D-fenfluramine challenge and improvement of
      psychopathology measured by the change in total BPRS score (p = 0.0004), in
      positive (p = 0.0403), negative (p = 0.0267), and anxiety-depression symptoms of
      BPRS (p = 0.0014). Our data support the original hypothesis that there is a
      relationship between 5-HT system activity and treatment response. The higher
      responsiveness of the 5-HT system in first episode, non-medicated schizophrenics,
      was associated with a poorer treatment response to haloperidol, an
      antidopaminergic neuroleptic.

PMID- 9542793
TI  - Prenatal exposure to influenza and schizophrenia in Surinamese and Dutch
      Antillean immigrants to The Netherlands.
AB  - There is evidence of an increased incidence of schizophrenia in Afro-Caribbean
      immigrants to the UK and in Surinamese- and Dutch Antillean immigrants to The
      Netherlands. We tested the hypothesis that second-trimester exposure to the 1957
      A2 influenza pandemic, which swept through the Caribbean in the same period as it
      affected Western Europe, contributes to this phenomenon. The dates of birth of
      immigrants, discharged from a Dutch psychiatric institute with a diagnosis of
      schizophrenia, were examined for any effect of the pandemic. Individuals who were
      in their second-trimester of fetal life at the peak of the pandemic were at no
      greater risk of developing schizophrenia than controls.

PMID- 9542794
TI  - A case of treatment-refractory psychosis responsive to sertindole.
AB  - Sertindole is an antipsychotic with atypical in vitro and ex vivo binding
      profiles and little propensity to cause extrapyramidal symptoms. However, its
      potential usefulness in the treatment of psychosis resistant to the 'classical'
      neuroleptics has not been determined. In the present study we used a double
      blind, placebo-controlled trial of sertindole and observed dramatic, sustained
      resolution of formerly-chronic positive and negative psychotic symptoms in a
      schizophrenic patient. This patient had averaged 2.5 inpatient admissions per
      year for the 8 years preceding initiation of sertindole therapy, but has had no
      hospitalizations or psychosis in the 3.5 years since. Improved cognitive function
      has also been documented. This preliminary, but controlled, experience suggests
      that sertindole may possess a spectrum of clinical activity distinct from that of
      the typical antipsychotic agent.

PMID- 9542795
TI  - Literary descriptions of the restless legs syndrome.

PMID- 9542796
TI  - Serotonin 5-HT3-receptor antagonist GR 38032F suppresses sleep apneas in rats.
AB  - The effects of administration of GR38032F, a 5-HT3 receptor antagonist, on
      spontaneous sleep apneas were studied in adult Sprague-Dawley rats by monitoring
      sleep, respiration and blood pressure for 6 hours. Intraperitoneal injection of
      GR38032F (1 mg/kg) suppressed spontaneous central apneas during non-rapid-eye
      movement (NREM) and especially during rapid-eye-movement (REM) sleep. This effect
      was associated with increased respiratory drive but did not cause cardiovascular
      changes at the dose tested. The suppressive action of GR38032F on spontaneous
      sleep apneas is analogous to findings in anesthetized rats in which 5-HT and 2
      methyl-5-HT provoked central apneas that were antagonized by GR38032 (Yoshioka et
      al, JPET 1992; 260:917-924). Our data implicate 5-HT3 receptor systems in
      determining sleep-related respiratory drive and apnea expression in rats, effects
      which are most probably mediated by vagal afferents.

PMID- 9542797
TI  - The effects of sensory stimulation on REM sleep duration.
AB  - Previous experiments have demonstrated that auditory (AS) and/or somatosensory
      (SS) stimulation can increase the duration of REM sleep periods in rats, cats and
      humans. The objectives of this study were to determine whether repeated AS
      stimulation causes habituation to the stimulus and whether any additive effects
      could be obtained with the simultaneous application of AS and SS. Three
      experimental procedures were used in this study. In experiment 1, animals were
      recorded for 4 consecutive days with AS, followed by a post-stimulus session. In
      experiment 2, they were recorded for 24 hours with AS applied at each REM period,
      followed by a subsequent 24-hours-post-stimulus recording. In experiment 3,
      animals underwent AS, SS stimulation, or simultaneous application of both in a
      random fashion at each REM period. The results of all experiments confirm
      previous findings showing that auditory or somatosensory stimuli significantly
      increase REM sleep period duration. In addition, AS--applied with different
      presentations during REM and throughout the sleep-wake cycle--are capable of
      increasing REM duration regardless of the manner in which they were presented.
      However, the effects of the stimuli were not additive. It is worth noting that
      although REM duration increased, REM period frequency decreased, resulting in no
      net change of total REM sleep through time. Furthermore, no changes were observed
      in other sleep-wake variables. These experiments clearly demonstrate that
      repeated auditory stimulation does not cause habituation, and there are no
      evident side effects on the sleep-wake cycle. These results confirm that the
      mechanisms involved in REM generation and maintenance can be modulated by sensory
      modalities.

PMID- 9542798
TI  - Developmental alterations in auditory arousal from sleep in healthy and virus
      infected cats.
AB  - To investigate the impact of respiratory-tract infections on arousability from
      sleep, we evaluated the auditory arousal responses of healthy and virus-infected
      cats in two age groups. Arousability was positively associated with stimulus
      intensity but negatively associated with experimental day. Infected animals were
      more responsive to auditory stimuli than were uninfected ones, and younger cats
      were less responsive than older animals. Within the younger groups, infected cats
      demonstrated increased arousability across the entire range of stimulus volumes
      during quiet sleep but not during active sleep. Young infected cats also
      demonstrated lower EEG delta-wave amplitudes than did uninfected animals. These
      effects on arousability and EEG amplitudes were not observed in older cats. Thus,
      under the conditions studied, cats with mild viral infections show an age-related
      enhancement of auditory arousability from sleep, suggesting that they sleep less
      deeply than do healthy, age-matched animals. The generalization of these
      observations to other arousing stimuli, such as hypoxia or hypercapnia, and
      possible implications for the pathogenesis of sudden infant death syndrome remain
      to be determined.

PMID- 9542799
TI  - Medium-intensity light produces circadian rhythm adaptation to simulated night
      shift work.
AB  - STUDY OBJECTIVES: To assess the effect of nocturnal light intensity on circadian
      adaptation to simulated night work. SETTING AND PARTICIPANTS: Normal young men
      and women, simulated night work, home sleep. DESIGN AND MEASUREMENTS: We compared
      temperature rhythm phase shifts following timed exposure to high (approximately
      5700 lux 3 hours/day), medium (approximately 1230 lux 3 hours/day) or constant
      low-intensity (< 250 lux) light during consecutive night shifts. Subjects (n =
      35) followed a schedule of 7 days baseline, 6 days of 8-hour night shifts (with
      day sleep delayed 10 hours from baseline sleep), and 4 days of recovery. Subjects
      wore dark sunglasses while outdoors during daylight. Sleep logs were completed
      after each 8-hour sleep/dark period. Night work fatigue was rated by
      questionnaire. RESULTS: During the 3rd through 5th days of night work, most
      subjects in the high and medium groups (100% and 85%) exhibited phase delays
      large enough that their body temperature minima occurred within the daytime
      sleep/dark period. Only 42% of subjects in the low group exhibited phase delays
      large enough to meet this criterion of circadian adaptation. The phase shifts of
      the high and medium groups were not significantly different, and were
      significantly different from the low group. Larger phase shifts were correlated
      with more sleep and less fatigue. CONCLUSIONS: Extremely "bright" light may not
      be necessary for circadian adaptation in shift work situations similar to our
      study protocol (e.g., regular daytime sleep/dark periods, sunglasses).

PMID- 9542800
TI  - Diurnal rhythm of fetal behavioral state.
AB  - To test for the presence in utero of diurnal periodicity in the amount of time
      spent in organized behavioral states, seven records of 24-hour duration were
      obtained from each of five chronically instrumented fetal baboons between 144 and
      158 days gestation (term = 175 days). Concordance of fetal breathing activity,
      heart-period variability, and electroencephalographic parameters were used to
      define two distinctive patterns of fetal physiological activities. One pattern
      was characterized as EEG activity dominated by trace alternant, reduced heart
      period variability, and fewer breaths in epochs of fetal breathing. This fetal
      behavioral state (1FB) is analogous to quiet sleep in infants. A second pattern
      was characterized by the relative absence of trace alternant, increased heart
      period variability, and fetal breathing activity. This fetal behavioral state
      (2FB) is analogous to active sleep. Cycles of these states were present 29% of
      time, with a duration of approximately 26 minutes and a 1.7:1 predominance of
      2FB/1FB. Cosinor analysis across fetuses revealed a significant (p < .01) 24-hour
      periodicity of the time spent by the fetus in organized behavioral states, with a
      peak around 1400 (lights-on 0700 to 1900) and a peak-nadir fluctuation of 15%.
      These periodicities in the incidence of organized state were significant (p <
      .01) in three fetuses, and approached significance (< .09) in the two others.
      Data demonstrate a diurnal rhythmicity in fetal behavioral states, with less time
      spent in organized state at night than during the day.

PMID- 9542801
TI  - Epidemiology of alcohol and medication as aids to sleep in early adulthood.
AB  - STUDY OBJECTIVES: In a representative sample of adults 18-45 years of age, this
      study addressed three questions about the use of sleep aids in the general
      population: (1) what are the past-year prevalences of the use of alcohol, over
      the-counter medication and prescription medication to facilitate sleep? (2) among
      those who use these substances for sleep problems, what are the patterns of use?
      and (3) are there social factors, independent of sleep characteristics, that
      increase the likelihood of alcohol and medication use to aid sleep? DESIGN: The
      1996 Detroit Area Survey was a random-digit-dial, computer-assisted survey of a
      representative sample of 2,181 adults ages 18-45 in the Detroit primary
      metropolitan statistical area. Eligible household response rate was 86.8%.
      RESULTS: In the general population, use of alcohol and medication as sleep aids
      in the past year was found to be fairly common: 13% used alcohol, 18% used
      medications and 5% used both. The prevalence of any substance use to aid sleep
      was 26%. The duration of use was short for the majority of users, less than 1
      week. However, duration of use was greater for the majority of those using
      prescription sleep aids. A substantial minority of users report regular use
      lasting longer than 1 month: 15%, 9%, and 36% for alcohol, OTC medications, and
      prescription medications, respectively. Both sociodemographic and sleep
      characteristics were associated with alcohol and medication use to aid sleep.
      Difficulty falling asleep was the factor most strongly associated with use of
      substances to improve sleep. Sex, race/ethnicity, work shift, marital status and
      education were also significantly associated with one or more types of sleep aid
      use adjusting for difficulty falling asleep.

PMID- 9542802
TI  - Evaluation of a computerized polysomnographic system.
AB  - Computerized polysomnographic systems have came into common use in sleep
      laboratories around the world. Despite potential advantages over standard paper
      polysomnography, these computerized systems have been minimally evaluated as to
      accuracy, analysis time, or cost effectiveness when compared to paper. We
      evaluated the Healthdyne ALICE 3 system for comparability to paper
      polysomnography in sleep quantification and technician analysis time. Fifty
      patients were recorded simultaneously both on paper and on the ALICE 3 system and
      analyzed blindly with summary data from these records being quantified and
      compared. Five additional patients were studied for epoch-by-epoch analysis.
      Score-rescore assessments were accomplished for both groups. The results indicate
      that when allowed to autoscore, this computerized system produced substantial
      errors in sleep staging (REM sleep time 56.4 + 4.9 minutes vs 73.2 + 8.4 minutes
      for paper versus computer). This was the case for respiratory (AHI of 26.5 + 4.3
      vs 15.3 + 2.6 for paper vs computer) and arousal assessment as well. However,
      with editing, similar results to those obtained with paper were achieved (REM
      sleep time -56.4 + 4.9 vs 59.0 + 4.6; AHI -26.5 + 4.3 vs 26.1 + 4.7 for paper and
      computer respectively), with differences rarely exceeding score-rescore
      discrepancies. Analysis time was substantially reduced by use of the computer
      (172.6 + 9.9 vs 79.7 + 4.8 minutes for paper vs computer). Epoch-by-epoch
      analysis revealed a trend to score toward wakefulness or lighter sleep on
      computer compared to paper although the differences were small. Respiratory,
      arousal and PLM scoring were quite similar. In conclusion, this study suggests
      that the ALICE 3 system with editing can produce results similar to those
      obtained with paper.

PMID- 9542803
TI  - Evaluation of the Healthdyne NightWatch system to titrate CPAP in the home.
AB  - Although a number of devices have been developed to monitor sleep and breathing
      in the home, there are few publications on methodologies by which CPAP can be
      titrated in the home setting. This study was conducted to determine the outcome
      of CPAP titration in the home using the Healthdyne NightWatch (NW) system. This
      home sleep-evaluation system was used to diagnose sleep apnea in 30 patients
      using a previously described methodology. These patients subsequently underwent
      CPAP titration in the home using the NW system, with modem technology allowing
      the transfer of data from the home to the laboratory. This group was compared
      with 30 patients who were diagnosed with sleep apnea using standard in-lab
      polysomnography and had CPAP titrated on a full night in the laboratory. Both
      groups were subsequently placed on CPAP at the appropriate pressure for 6-8
      weeks, after which a full in-lab study was completed to assess CPAP efficacy at
      the prescribed pressure. Compliance was also determined using a pressure
      activated monitor. No differences in any variable assessed could be found between
      the two groups. Mean compliance was 4.6 + 0.5 (SEM) and 4.3 + 0.5 hours of CPAP
      use per night for the home and in-lab groups respectively. Mean AHIs on the
      follow-up study were 7.4 + 1.2 and 7.6 + 1.6 events per hour for the home versus
      in-lab groups. Sleep stage distribution was also quite comparable between groups.
      As a result, this study suggests that sleep apnea can be diagnosed and CPAP
      titrated in the home with a similar outcome, at least at 6 to 8 weeks, to
      standard in-laboratory testing.

PMID- 9542804
TI  - Direct comparison of two widely used activity recorders.
AB  - Wrist actigraphy is increasingly used to track circadian rest-activity cycles and
      to identify states of wakefulness and sleep, yet the measurement characteristics
      of activity recorders have never been compared. Two widely used recorders are
      compared here: the MotionLogger from Ambulatory Monitoring, Inc (AM) and the
      Gaehwiler (G). They were worn together on the same wrist for periods averaging
      41.5 hours by five members of a research team. Activity counts were stored every
      half-minute. Pairwise comparisons between recorders of each type showed both
      types to be reliable. Each also validly detected circadian rest/activity cycles.
      Both types suffered, however, from insensitivity. For the lower 75% of activity
      levels, the variance of data from the G was indeed so small as to be essentially
      uninformative. Since these levels include over 95% of all nocturnal data, the G
      must be less sensitive than the AM to small nocturnal movements, including those
      signifying arousal. An additional difference is that data from the AM but not the
      G were distributed in biphasic fashion. Biphasic activity levels are consistent
      with the common assumption that activity/wakefulness and rest/sleep are distinct
      neurobehavioral states. As the use of actigraphy increases, the important
      differences found here between two leading instruments point to an urgent need
      for standards by which activity recorders can be compared. Aspects of instrument
      design that could be quantitatively rated are reliability, validity, ruggedness
      and artifact rejection.

PMID- 9542805
TI  - Bibliography of recent literature in sleep research.

PMID- 9542806
TI  - [Activities of the enzymes LDH, gamma-GT, GOT, GPT and lactoperoxidase in the
      milk of breeding mares during the course of lactation].
AB  - Milk samples were collected from 44 mares (trotters, warm blood horses, quarter
      horses) during lactation between the 1st and 90th day p.p. at 20 defined days.
      The activity of the enzymes LDH, gamma-GT, GOT, GPT and lactoperoxidase was
      investigated. The aim of this study was to find out the changes of these
      parameters during lactation and whether an influence of race, conception, date of
      foaling, age and number of lactations existed on the enzyme activities in mare's
      milk. The following results were obtained: In mare's milk the LDH-activity was
      highest (xg = 629 x 1.5 +/- 1 U/l) on the 1st day p.p. and showed a marked
      decrease on the 3rd day p.p. followed by a slight decrease until the 20th day
      p.p. It remained then at a constant level of about 80 U/l. The lowest activity
      (xg = 65.2 x 1.51 +/- 1 U/l) was measured on the 76th day p.p. The influence of
      conception and date of foaling time were statistically significant. The gamma-GT
      activity was highest on the 3rd day p.p. (xg = 143.4 x 1.45 +/- 1 U/L) and
      decreased during lactation. The lowest activity was measured on the 90th day p.p.
      (xg = 23.2 x 1.51 +/- 1 U/L). The influence of race and conception--time were
      statistically significant. The GOT-activity of the 1st day p.p. (xg = 38.3 x 1.77
      +/- 1 U/L) was higher than in mature milk. After the 3rd day p.p. activities
      between 15.5 x 1.38 +/- 1 U/l and 11.9 x 1.38 +/- 1 U/L were measured. The GPT
      activity was highest on the 1st day p.p. (xg = 37.5 x 1.81 +/- 1 U/L) and
      decreased on the following days. After the 9th day p.p. activities between 9.1 x
      1.37 +/- 1 U/l and 8.5 x 1.32 +/- 1 U/l were found. The influence of age, race,
      race (time, date of foaling (time and conception (time were significant. No
      Lactoperoxidase activity could be found in mare's milk. The origin and importance
      of the mare's milk enzymes are discussed.

PMID- 9542807
TI  - [Protein patterns of Pasteurella multocida strains in relation to the animal host
      and the geographic site of isolation].
AB  - Protein patterns from 681 Pasteurella multocida strains of different animal
      species and distinct geographical regions were analyzed by PAGE. We found 9
      protein types taking the most intense band as reference. This band represents a
      protein of the outer membrane (OMP). In assigning the strains to protein types a
      relation to animal hosts of the strains was established. The majority of isolates
      from rabbits (88%) belongs to type P6, which is not found in strains isolated
      from cattle or pigs. Strains from pigs did not include the protein types P2, P4
      and P8, in cattle strains type P9 was absent. The distribution of protein types
      in bovine isolates was shown to be related to the geographical location. The
      results are discussed with particular emphasis on immuno-prophylaxis. It appears
      promising to develop P. m. vaccines specific for certain animal species.

PMID- 9542808
TI  - [Characterization of viral hemorrhagic septicemia (VHS) virus isolates in trout].
AB  - Virus diseases of fish can seriously impair the economy of aquacultur. Control
      and prevention of fish diseases in the European Union (EU) are focussed on the
      viral haemorrhagic septicaemia (VHS) and the infectious haematopoeitic necrosis
      (IHN). The diagnosis of VHS and IHN is performed in the Federal Republic of
      Germany (FRG) on the basis of the legislation of the EU. Since 1994 we received
      an increasing number of VHS virus (VHSV) isolates which did not react with a
      commercially available anti-VHSV monoclonal antibody (MAb) in the indirect immuno
      fluorescence test. With our own MAb ID8, however, as well as with additional
      diagnostic methods these virus isolates could be identified. These isolates of
      rainbow trouts were designated as VHSV type "Wi". Electron microscopically all
      stages of rhabdovirus maturation could be detected. Morphologically the isolates
      were undistinguishable from other rhabdoviruses. By immuno electron microscopy
      using the MAb ID8 rhabdovirus nucleocapsid structures were demonstrated. The
      virulence of the new VHSV type Wi was not different from that of a VHSV isolate
      with conventional reaction patterns as well as of a VHSV laboratory strain.

PMID- 9542809
TI  - [A case of Echinococcus granulosus hydatid cyst in a zoo born dromedary in the
      Berlin-Fridrichsfelde zoo].
AB  - In Germany, the threat to human health by the small fox tapeworm (Echinococcus
      multilocularis) has been increasingly discussed in the last few years. On the
      other hand, the hydatid worm of the dog (Echinococcus granulosus) became more and
      more rare in Germany and was often declared to be eradicated. This paper presents
      a case of hydatid infection of the lung in an adult dromedary (Camelus
      dromedarius), which was born and kept all its life at Tierpark Berlin
      Friedrichsfelde. Questions connected with E. granulosus infection are discussed
      from an ecological point of view: history, urbanisation, biology, clinical signs,
      potential threat to man, prophylaxis and treatment. In view of the extensive and
      sometimes uncontrolled dog keeping in urban households it must be stressed that
      careful documentation and surveillance of this life-threatening zoonosis, which
      was the main reason for its decline in the past, has not yet lost its importance.

PMID- 9542810
TI  - [Digital and analog radiographic techniques in the case of thoracic diagnosis].
AB  - Up to now digital luminescens radiography has not been used widely in veterinary
      medicine. This paper gives an overview of the first experiences with the
      application of the digital ADC-System (Agfa Diagnostic Center) for imaging
      pulmonary nodules and other lung diseases in dogs in comparison to the
      conventional method. For this, we used radiographs of dogs of several weight
      groups with lung diseases. To compare both systems (conventional and digital) we
      took pictures with either method in the same positioning. Compared to the analog
      film screen system, the phosphor storage radiographs enhance the detection of
      fine details. Additionally, the digital technology gives an opportunity for post
      processing of image data in order to optimize the discrimination of various image
      details and offers a wide latitude for exposure, which means less retakes and a
      wider range for dose selection. The advantage of digital filing stations is on
      the one hand the possibility of space saving and storage unlimited by time, on
      the other hand it offers the possibility to recover X ray pictures in very short
      time.

PMID- 9542811
TI  - [Treatment of hypertensive insulin-resistant patients is a difficult decision to
      make. Metabolically neutral drugs should be the choice of treatment].

PMID- 9542812
TI  - [Risk of depression may be discovered by sleep. The sleep pattern is predictable
      and possible to manipulate].

PMID- 9542813
TI  - [Heart rehabilitation in Nynashamn. Life-saving activities may be closed down].

PMID- 9542814
TI  - [Maintain medical ethics!].

PMID- 9542816
TI  - [Quality and/or safety of health care].

PMID- 9542815
TI  - [The art of reading a debate on the treatment of schizophrenia].

PMID- 9542817
TI  - [The rattlesnake is not more dangerous than the viper].
AB  - The article consists of a comparison of the effects of snakebites inflicted by
      North American rattlesnakes and those of European vipers, based on a review of
      series of snake bite victims reported in the literature since 1980. The two
      groups of snakebites were found to manifest close similarity, even regarding the
      currently low fatality rates. Whereas local reactions seem to be more extensive
      after rattlesnake bites, circulatory symptoms including severe hypotension appear
      to be more common after viper bites. It is concluded that the two groups of
      snakes may be regarded as equally dangerous.

PMID- 9542818
TI  - [For a long time it was believed that "giants on Earth" were ancestors of
      humans].

PMID- 9542819
TI  - [Cultural aspects of pain: pain behavior--symptom or communication?].

PMID- 9542820
TI  - [Is antihypertensive treatment a risk factor of coronary disease? Therapy-related
      triglyceride increase nor diabetes increase the risk].
AB  - In an observational study designed to determine whether metabolic changes during
      long-term antihypertensive drug treatment are associated with an increased risk
      of coronary heart disease (CHD), 686 middle-aged hypertensive men recruited from
      a random population screening sample were followed up for 15 years.
      Antihypertensive treatment predominantly consisted of beta-adrenoceptor blockers
      and/or thiazide diuretics. CHD and diabetes mellitus were checked for at annual
      examinations. Time-dependent Cox regression analysis was used to determine
      correlation between the incidence of CHD and entry characteristics, the monitored
      serum levels of cholesterol and triglyceride concentrations and the development
      of diabetes mellitus. Univariate analysis showed the presence of diabetes
      mellitus a entry to the study and increased baseline serum concentrations of
      cholesterol and of triglycerides each to be a significant predictor of CHD, the
      respective relative risks (RR) being 2.12, 1.21 and 1.21. However, analysis of
      monitored levels of metabolic variables during follow-up showed only an increased
      serum cholesterol concentration to be significantly and independently associated
      with CHD (RR 1.07). Although serum triglyceride concentrations increased slightly
      during follow-up, they were unrelated to the incidence of CHD; nor was onset of
      diabetes mellitus during follow-up significantly associated with an increased
      risk of CHD (RR 1.48. Thus, the study showed the presence of metabolic
      disturbances such as diabetes mellitus and hyperlipidaemia before the start of
      antihypertensive treatment to be of positive predictive value in middle-aged
      hypertensive men, and an increase in the monitored serum cholesterol level to be
      an independent predictor of CHD, whereas neither drug-related diabetes nor an
      increase in the monitored serum triglyceride concentration seemed to be
      associated with the occurrence of CHD.

PMID- 9542821
TI  - [Gynecologic examination, a role-playing for two].
AB  - Although pelvic examination (PE) is a common procedure in gynaecological
      practice, there is little discussion among gynaecologists about the decision
      making process and the possible indications and contraindications. Moreover,
      examiners need to be aware that their approach and body language during PE will
      inevitably reflect their attitude toward women. At PE, there is tacit agreement
      between the examiner and the patient involving a cognitive restructuring of the
      situation. However, if memories of earlier experiences bearing some resemblance
      to the PE situation are aroused in the patient, and the emotions connected with
      them reactivated, she may become overwhelmed by the intensive reactions
      triggered. In such cases, the examiner needs to be able to recognise what is
      happening and provide the support the patient needs. Other responsibilities of
      the examiner at PE include recognising symptoms of post-traumatic stress
      reactions and vaginismus. In performing a young woman's first PE, the examiner's
      primary aim should be provide the experience; that PE is a benign procedure,
      unconnected with pain or distress; as the patient's experience at her first PE
      will inevitably influence all future examinations. Learning to perform a PE in
      such a way that it is beneficial to the patient in all these respects is an
      intricate and challenging task. However, experience with students and
      gynaecological teaching associates suggests that such skills can be taught and
      learned. The PE situation is charged with latent salubrious potential, which is
      usually insufficiently exploited.

PMID- 9542822
TI  - [Pain analysis is vital in rheumatic diseases. The pain is often the patient's
      worst problem].
AB  - The article consists of a synthesis of a rheumatic pain symposium held at the
      annual meeting of the Swedish Medical Association in 1996. Various aspects of
      pain in rheumatic diseases were discussed, such as physiological, neurohumoral
      and neurogenic mechanisms, sensory stimulation treatment, differentiation of
      mechanical and inflammatory pain, quality enhancement by improved cooperation
      between primary and tertiary care facilities, pharmacological treatment with
      (centrally and peripherally acting) opioids, selective cyclo-oxygenase
      inhibitors, and NMDA (N-methyl-D-aspartate) receptor antagonists. The aim of the
      symposium, with its focus on the manifest pain problem, was to improve our
      knowledge and skill in the understanding and treatment of this large patient
      category. For patients with rheumatic disorders exacerbated by pain problems, as
      for other patients, a pain diagnosis is of fundamental importance. This can be
      achieved by analysis of the social, psychological, physiological and medical
      factors contributing to the cause and degree of pain and to pain behaviour, and
      of the extent to which the pain may be nociceptive (i.e., inflammatory,
      mechanical, or ischaemic in origin), neurogenic or idiopathic. Pain analysis
      should be followed by individualised treatment focused on the patient's most
      crucial problems, thus enhancing the prospect of optimal treatment outcome.

PMID- 9542823
TI  - [Radiation-induced hemorrhagic proctitis treated with formalin. A simple and
      efficient help against adverse effects of radiation].

PMID- 9542825
TI  - [How much more care do the elderly need when compared to the younger? The age
      weighting differences are difficult to understand].

PMID- 9542824
TI  - [Hemicraniectomy in malignant mid-cerebral infarction. Further trials needed
      before its acceptance in clinical practice].
AB  - In cases of completed middle cerebral artery territory stroke, prognosis is very
      poor and the clinical course is characterised by a rapid decline in consciousness
      and signs of herniation 2-4 days after the onset of symptoms due to a space
      occupying mass. Failure of conservative therapy is the rule, and herniation is
      the usual cause of death, occurring in almost 80 per cent of cases. Recently
      published results have suggested that hemicraniectomy may improve survival in
      patients with massive hemisphericstroke, decreasing mortality to less than 35 per
      cent. The article presents what is probably the first case to be reported in
      Sweden, where hemicraniectomy was performed on a 45-year-old woman with right
      hemispheric completed middle cerebral artery infarction.

PMID- 9542826
TI  - [Child welfare. Concentration on education, research and service].

PMID- 9542827
TI  - [Stem cell transplanted to fetus].

PMID- 9542828
TI  - [DNA contaminated drugs may be the cause of antibiotic resistance. Insufficiently
      purified preparations are carriers of danger].

PMID- 9542829
TI  - [Surgery for cleft lip and palate should benefit from centralization. Experts of
      social medicine should also be included in the team].

PMID- 9542830
TI  - [The new occupational health services and ethics. Are physicians in occupational
      health services reliable?].

PMID- 9542831
TI  - [Physicians should respect work of their colleagues].

PMID- 9542832
TI  - [Persons with self-destructive behavior may have been sexually abused as
      children].

PMID- 9542833
TI  - [First generation cephalosporins are not suitable in bacterial respiratory tract
      infections].

PMID- 9542834
TI  - [Important questions in connection with "How dangerous is health care service"?].

PMID- 9542835
TI  - [Surgery or training in urinary incontinence?].

PMID- 9542836
TI  - [Improved treatment of cleft lip and palate is now available].
AB  - When cleft lip and palate treatment was introduced at Gothenburg in 1957, the
      procedure used was early bone grafting (EBG). By 1965, EBG had been omitted from
      the regimen, bone grafting being postponed until the appearance of mixed
      dentition. Analysis of the results of both techniques showed maxillary retrusion
      of different degrees. Accordingly, this routine was abandoned in 1975, being
      replaced by a procedure which is characterised by delayed closure of the hard
      palate (DCHP). Thus, the surgical procedure comprised the following steps: 1, lip
      closure at 1-2 months of age; 2, soft palate repair at 6-8 months; 3, final lip
      nose surgery at 12 months; and 4, closure of the left in the hard palate, and
      bone grafting to the alveolar process during mixed dentition at about 8-10 years
      of age. Follow-up has shown the majority of patients to manifest acceptable
      speech development during childhood, though problems may occur in some cases.
      Maxillary growth has been found to be improved after DCHP, and at present the
      need of maxillary advancement surgery has been reduced to approximately 5% of
      cases, as compared with the former rates of 50% of cases among those treated with
      EBG, and of 25% among those treated with the vomer flap procedure.

PMID- 9542837
TI  - [Parturients are under-treated. Only 21 out of 55 clinics administer oxytocics
      routinely during the third stage of labor].
AB  - A questionnaire answered by all 55 Swedish labour wards in 1995 showed oxytocic
      treatment to be given routinely to all parturients during the third stage of
      labour at only 38% (21/55) of the units, and that five of these 21 units were
      considering cessation of the practice. At a further 25 units the treatment was
      given routinely only in selected risk cases, the most common risk factors being a
      history of postpartum haemorrhage (a criterion at 20 units), multiple pregnancy
      (14 units), prolonged labour (12 units), and a large baby (8 units). Of the
      remaining nine units, where oxytocic treatment was given only on clinical
      indications (i.e., postpartum haemorrhage), two were considering the introduction
      of routine treatment. In view of results obtained in a recent randomised, placebo
      controlled Swedish study, the authors of the article conclude that, if clinical
      practice in this respect has remained unchanged since the questionnaire study was
      performed, Swedish parturients are undertreated with oxytocics during the third
      stage of labour.

PMID- 9542838
TI  - [A study of young offenders undergoing forensic psychiatric evaluation. There is
      a need of correctional care alternatives].
AB  - With effect from January 1, 1992, legislation regulating the practice of forensic
      psychiatry in Sweden, the Forensic Mental Care Act, was changed to meet more
      restrictive demands. A retrospective study of 15-20-year-old male offenders,
      investigated at the Dept. of Forensic Psychiatry in Stockholm during the period
      1990-93, showed the proportion sentenced to forensic psychiatric care to have
      decreased by 21 per cent since the introduction of the new legislation. The
      majority of young offenders otherwise sentenced, mainly to correctional
      treatment, were suffering from personality disorders. Most of them had previously
      been in contact with the correctional and social service sectors. Several of them
      received prison sentences despite the fact that young offenders are not to be
      sent to prison without exceptional reasons. One such exceptional reason might be
      the lack of an appropriate alternative. A third treatment alternative is called
      for.

PMID- 9542839
TI  - [Association of parents of children with diaphragmatic hernia: prenatal diagnosis
      -a right for all who want it].

PMID- 9542840
TI  - [Simpler prenatal diagnosis results in new ethical problems. Blood tests of
      pregnant women may detect Down syndrome].

PMID- 9542841
TI  - [An analysis of mortality in Sweden during 1987-1994: no overmortality among
      persons born outside the Nordic countries].

PMID- 9542842
TI  - [Careful optimism when it comes to xenotransplantations].

PMID- 9542843
TI  - [The picture of the psychiatrist should be more nuanced. General practitioners
      react to articles on depression in primary health care].

PMID- 9542844
TI  - [More than 20,000 adolescents start smoking every year. Is school-based
      prevention a possible way?].

PMID- 9542845
TI  - [Hippocrates' ethics are still of current interest].

PMID- 9542846
TI  - [Hippocrates' ethics still up to date? No, it should be re-evaluated!].

PMID- 9542847
TI  - [Death in literature].

PMID- 9542848
TI  - 1st Croatian Congress on Atherosclerosis. Brijuni Islands, Croatia, September 30
      October 3, 1997. Abstracts.

PMID- 9542849
TI  - Treatment of the wounded at Chipyong-ni.
AB  - The battle fought by a U.S.-French force at Chipyong-ni in mid-February 1951 has
      been called the turning point of the Korean War, and may have been the first time
      that transfusions of whole blood were given as far forward as the regimental area
      during combat. The surgeon, or chief medical officer, of the United Nations force
      at Chipyong-ni describes this and other measures required by the tactical and
      medical situations there, and illustrates how they were made possible, in large
      part, because an important lesson learned during World War II had been applied:
      the surgeon had direct access to the commander as a member of his staff, and
      controlled the task force medical facilities.

PMID- 9542850
TI  - Co-occurrent use of cigarettes, alcohol, and caffeine in a retired military
      population.
AB  - Previous studies have linked the use of caffeine, nicotine, and alcohol to health
      complications and have also found that the use of these substances significantly
      covary. Given the prevalence of health problems of older adults, it is surprising
      that no studies to date have examined the co-occurrent use of alcohol, caffeine,
      and nicotine in a senior population. This investigation evaluated the co
      occurrent use of cigarettes, caffeine, and alcohol in a community sample of older
      Americans. Respondents (1,095 women and 1,371 men) completed a questionnaire
      examining their use of caffeine, nicotine, and alcohol. This study replicated
      earlier findings that tobacco, caffeine, and alcohol use co-occur and that there
      are consistent use patterns for these substances. The results suggest that health
      organizations could better target services by prescreening for smoking, alcohol,
      and caffeine use and possibly targeting smokers and ex-smokers for potentially
      problematic use patterns of caffeine and alcohol.

PMID- 9542851
TI  - The impact on a health care system of a program to facilitate self-care.
AB  - BACKGROUND: High utilization for self-limiting conditions has challenged health
      care systems to be innovative. The facilitation of self-care has been identified
      as a viable concept to control demand and encourage efficient use of resources. A
      Self-Care Intervention Program (SCIP) coupled with a Health Promotion Pharmacy
      (HPP) was implemented in an Army health care system to determine the impact on
      the use of self-care. METHODS: A questionnaire was mailed to 283 SCIP
      participants at the 6-month interval to assess achievement of program objectives.
      Use of the HPP was documented during the same interval. The response rate was
      67.5% (n = 191). RESULTS: A positive response was obtained for all six program
      OBJECTIVES: Increased knowledge of personal health issues (84.3%); increased
      confidence to treat minor illnesses (77%); improved opinion of the health care
      system (74.9%); increased practice of healthy behaviors (64.9%); and an increased
      commitment to seek preventive medicine (62.8%). Seventy-two percent of the
      respondents reported avoiding at least one clinic visit, and 39.8% reported
      avoiding at least one visit to the emergency room. The calculated return on
      investment was 11:1. CONCLUSION: A formal self-care program supported by a
      pharmacy can have a positive effect on participants' health and health care,
      resulting in cost-effective demand management.

PMID- 9542852
TI  - A comparison of 5-minute povidone-iodine scrub and 1-minute povidone-iodine scrub
      followed by alcohol foam.
AB  - The purpose of this study was to determine if a 1-minute scrub with povidone
      iodine followed by alcohol foam is as effective as a 5-minute scrub with povidone
      iodine in reducing skin bacterial counts. A 1-minute scrub with povidone-iodine
      followed by alcohol foam and a 5-minute scrub with povidone-iodine was done. In
      the first study, cultures were obtained after 1 hour, and in the second study,
      cultures were obtained after 2 hours. Cultures were obtained by imprinting the
      first, second, and third fingers on nutrient agar plates. Bacterial counts were
      then obtained at 24 and 48 hours. The study involved two groups of 12
      participants and a total of 37 patients over a period of 5 months. The results
      show that there was no significant difference between the number of colonies
      cultured for the 1-minute scrub compared with the 5-minute scrub for either the 1
      hour or the 2-hour study. In fact, the total number of bacterial colonies was
      less after the 1-minute scrub with alcohol foam than after the standard 5-minute
      scrub in both the 1-hour group (10 vs. 18) and the 2-hour group (18 vs. 44).

PMID- 9542854
TI  - Dental utilization by spouses of active duty U.S. military personnel.
AB  - This study explores dental utilization and access barriers to dental care for
      spouses of active duty U.S. military personnel as reported by their military
      sponsor. It also compares dental utilization of spouses and civilians. The data,
      collected using self-administered questionnaires between April 1994 and January
      1995, are from 5,732 Army, Air Force, Navy, and Marine personnel with nonmilitary
      spouses. Comparative civilian data are from the most recent (1985-1986) U.S. oral
      health survey of working adults. Results show that dental utilization of military
      spouses parallels that of civilians. Cost was the most commonly cited barrier to
      dental care for spouses. Logistic regression results show that the likelihood of
      a spouse having seen a dentist within the past year is influenced by insurance
      status, sex, branch of service of sponsor, and rank of sponsor. Insurance status
      is the strongest predictor of dental utilization for spouses.

PMID- 9542853
TI  - Comparing annual dental utilization rates of active duty U.S. military personnel
      and their employed civilian cohorts.
AB  - This study compares annual dental utilization rates between a representative
      sample of active duty U.S. military personnel (N = 11,765) and a national sample
      of employed U.S. civilians (N = 10,798). Military data were collected between
      April 1994 and January 1995 at 26 sites using self-administered questionnaires on
      a prestratified, random sample of Army, Air Force, Navy, and Marine personnel.
      Women and blacks were oversampled. Civilian data are from the most recent U.S.
      oral health survey of working adults. Results show that annual dental utilization
      rates of service members exceed those of their employed civilian cohorts.
      Overall, 86% of active duty military personnel have seen a dentist in the past
      year versus barely half of employed civilians. For service members, annual dental
      utilization is invariant across age, sex, race, education, branch of service, and
      rank. Dental health class and perceived need for dental care are inversely
      related to annual dental utilization.

PMID- 9542855
TI  - The need for and prevalence of dental sealants in active duty U.S. military
      personnel.
AB  - This paper explores the need for and the prevalence of dental sealants in active
      duty U.S. military personnel. The data come from the 1994 Tri-Service
      Comprehensive Oral health Survey. Data were collected on 13,050 Army, Air Force,
      Marine Corps, and Navy active duty personnel at 26 sites. Women and minorities
      were oversampled. Both bivariate and logistic regression analyses were done on
      the need for at least one dental sealant and the prevalence of at least one
      dental sealant in service members. Weighted data (1,669,662) were used for the
      bivariate analyses; unweighted data were used for the regressions. Results show
      that 3.6% of service members need dental sealants and that 6.8% have dental
      sealants. The need for dental sealants varies across age, rank, and branch of
      service. The prevalence of dental sealants varies across age, race, rank, and
      branch of service. The cost-effectiveness of dental sealants in this population
      should be established.

PMID- 9542856
TI  - Performance of the universal portable anesthesia complete vaporizer with
      mechanical ventilation in both drawover and pushover configurations.
AB  - Currently, a mechanical ventilator that can be adapted to the Universal Portable
      Anesthesia Complete (UPAC) vaporizer and anesthetic delivery system does not
      exist. The need for the anesthetist to concentrate on drug delivery and fluid
      resuscitation for the combat casualty in the field setting provides an expedient
      for the adaptation of a ventilator to the UPAC system. The purpose of this study
      was to determine whether the performance of the UPAC vaporizer was significantly
      altered when mechanical ventilation was provided in a drawover versus a pushover
      configuration, and to provide vaporizer performance curves for ventilatory
      parameters common for mechanical ventilation. The Ohio V5A and Lifecare PLV-100
      ventilators were used in controlled benchwork analysis. The results of the
      comparison between the two ventilators indicated that there was no significant
      difference in vaporizer output between drawover and pushover configurations. The
      data indicated that vaporizer output could be reliably predicted in either mode
      and was correlated with tidal volume and respiratory rate.

PMID- 9542857
TI  - Clinical evaluation of pushover mechanical ventilation with the Ohmeda Universal
      Portable Anesthesia Complete vaporizer.
AB  - Previous studies have not demonstrated the usefulness of a mechanical ventilator
      with the Universal Portable Anesthesia Complete (UPAC) field anesthesia delivery
      system in a pushover mode. This study demonstrated that the Lifecare PLV-100
      ventilator can function effectively in a practical pushover configuration with
      the UPAC vaporizer. By comparison, vaporizer output followed the patterns of
      documented concentration curves for isoflurane at a given dial setting and minute
      ventilation. Measured airway pressures in the breathing circuit were within
      physiological parameters.

PMID- 9542858
TI  - Recognition and treatment of osteosarcoma in the military health care system.
AB  - Forty-two patients with high-grade intramedullary osteosarcoma treated at Walter
      Reed Army Medical Center between 1985 and 1995 were reviewed to determine what
      effects military "managed health care" had on diagnosis, treatment, and outcome.
      Five-year survival was 61% overall (SE +/- 9.9%), despite local disease control
      obtained in 95% of patients. There was a statistically significant difference
      between active duty members and dependents in time to diagnosis (p = 0.008), yet
      there was no significant difference in survival between the two groups. Five-year
      survival in our patient population was slightly lower than 5-year survival
      reported in some large civilian medical centers despite good local disease
      control and intensive multiagent chemotherapy. Delays in diagnosis and military
      status had no apparent effect on survival, although limb salvage was not possible
      in nearly 40% of patients because of tumor size, disease extent, and involvement
      of neurovascular structures.

PMID- 9542859
TI  - Radiographic characteristics of the vesicourethral anastomosis after radical
      retropubic and perineal prostatectomy.
AB  - A fundamental difference between the surgical techniques of radical retropubic
      and radical perineal prostatectomy is the method by which the vesicourethral
      anastomosis is accomplished. In the latter procedure, because the anastomosis is
      performed under direct vision, some authors have suggested that continence may be
      improved while reducing the risk of obstruction. The merit of this observation
      has not been established. To evaluate the characteristics of the vesicourethral
      anastomosis in retropubic and perineal prostatectomy, postoperative cystograms of
      59 patients who underwent these procedures were reviewed in a blinded fashion. A
      normal, tapering bladder neck to the proximal urethra was noted in 80% of
      patients undergoing perineal prostatectomy compared with 2% of patients
      undergoing the retropubic approach. Various grades of diamond-shaped or bulbous
      irregularity of the vesicourethral anastomosis were seen in 98% of patients
      undergoing retropubic prostatectomy, and a system of grading of these
      abnormalities was established. These data suggest that a more physiologic
      appearing bladder neck and proximal urethra is achieved with radical perineal
      prostatectomy. Further study is required to determine the impact of this
      radiologic finding on urinary function and continence.

PMID- 9542860
TI  - Nomograms to follow recovery rate in status asthmaticus in a veteran population.
AB  - Data from 12 Department of Veterans Affairs patients hospitalized for status
      asthmaticus were analyzed to determine the rate and degree of response to
      therapy. The time to achieve recovery was directly related to the level of
      baseline obstruction at the time of hospital admission. The recovery rate was
      constant and could be described by a single second-degree polynomial regression
      equation. Nomograms were constructed showing this rate of improvement of
      pulmonary function over time at four levels of baseline pulmonary obstruction.

PMID- 9542861
TI  - Prevalence of sinusitis in young asthmatics and its relation to bronchial asthma.
AB  - In this paper, we present data on the prevalence of sinusitis and its
      relationship to bronchial asthma in 120 young male asthmatics evaluated without
      exacerbations of their disease. All patients reported respiratory symptoms during
      the preceding year, and in the most of them (74%), the severity of asthma was
      mild. Sinusitis was observed in 52 patients (43.3%), and the maxillary sinus was
      involved in 36 asthmatics. Sixteen of 52 patients with sinusitis had never had
      nasal symptoms of rhinitis. In all patients, physical examination of the lung was
      negative for wheezing. All patients had FEV1 (forced expiratory volume/forced
      vital capacity x 100 in 1 second of expiration) values in the normal range, and
      bronchial hyperresponsiveness was detected in 101 asthmatics (84.2%). One hundred
      sixteen patients (96.6%) were found to be skin reactors. We did not find
      statistical differences between asthmatics with or without sinusitis with regard
      to severity of asthma, basal lung function, and bronchial hyperresponsiveness. We
      suggest that antibiotic therapy for sinusitis should be given only to asthmatics
      with worsening respiratory symptoms and obvious signs of chronic sinusitis.

PMID- 9542862
TI  - Multiple giant cell tumors in a patient with Gulf War syndrome.
AB  - "Persian Gulf syndrome" refers to a group of clinical findings found in military
      personnel who served in the Persian Gulf War. The most commonly reported symptoms
      include chronic fatigue, headache, and neurologic disorders. Recently, new
      information has linked Whipple's disease and Ki-1 anaplastic large cell lymphoma
      to this syndrome. Presented here is an unusual case of multiple giant cell tumors
      of the hand in a patient with documented Persian Gulf syndrome. The epidemiologic
      significance between these two entities is unclear, because this is a single
      reported case. However, the practical message is clear. Physicians must
      meticulously evaluate patients who are veterans of the Persian Gulf conflict to
      further our understanding and confirm the existence of this syndrome.

PMID- 9542863
TI  - Fibrous dysplasia of the clivus and sphenoid sinus.
AB  - Fibrous dysplasia is a primary disease of bone that may lead to bony distortion,
      expansion, and weakness. Craniofacial involvement is an important entity for
      physicians to be aware of because of the potential for impingement on
      neurovascular structures, intracranial extension, and cosmetic deformity. We
      report two cases of craniofacial fibrous dysplasia and discuss the clinical
      presentation, radiographic and histologic findings, and the management of
      affected patients.

PMID- 9542864
TI  - [Glomerulonephritis caused by acute serum sickness].
AB  - A 51-year-old male patient was treated for a rejection episode after kidney
      transplantation with horse antithymocyte globulin (ATG). Twelve days after the
      start of the ATG treatment he developed fever, arthralgia, purpura and acute
      renal failure. This clinical picture is characteristic of serum sickness,
      resulting from formation of antibodies to a foreign protein and development of
      immune complexes. Kidney biopsy revealed an endocapillary glomerulonephritis.
      Immune complexes probably develop in the mesangium and along the glomerular basal
      membrane through local formation and precipitation from the circulation.
      Spontaneous recovery is the rule.

PMID- 9542865
TI  - ['Open season in the hunt for poliovirus' (continued)].
AB  - Global eradication of poliomyelitis was started in 1988. Polio eradication is
      considered feasible on theoretical and practical grounds, is cost-effective and
      is endorsed at the highest political levels. The strategy is based on (a)
      increasing vaccination coverage through routine immunization, national
      immunization days and so-called mopping-up campaigns, (b) improving surveillance,
      and (c) polio-free certification. Since the start of the programme global
      vaccination coverage increased from 67% in 1988 to 83% in 1995; the number of
      reported cases--an estimated 10% of the total number--decreased by 90% from
      35,251 (1988) to 3,755 (1996). A rapid further decrease is expected with the
      start of national immunization days on the Indian subcontinent. In the next years
      the emphasis will be strongly on surveillance i.e. detection of possible polio
      patients and (wild) poliovirus circulation. All countries will need to implement
      reliable surveillance to show their polio-free status. Only then can the world be
      declared polio-free.

PMID- 9542866
TI  - [Side effects of minocycline in the treatment of acne vulgaris].
AB  - Minocycline is the most commonly used systemic antibiotic in the long-term
      treatment (weeks to months) of severe acne vulgaris. Currently much attention is
      being paid in the Dutch and international literature to the safety of
      minocycline, after several reports on serious adverse events. The clinical
      efficacy of minocycline in the treatment of acne vulgaris is better than that of
      tetracycline and equal to that of doxycycline. The serious adverse events of
      minocycline therapy described consist of hyperpigmentation of various tissues,
      autoimmune disorders (systemic lupus erythematosus, autoimmune hepatitis) and
      serious hypersensitivity reactions (hypersensitivity syndrome reaction,
      pneumonitis and eosinophilia, and serum sickness-like syndrome). In relation to
      the number of prescriptions, the number of serious adverse events of minocycline
      described is small. However, it is very important that prescribing doctors should
      be aware of the possibility of these adverse events occurring during long-term
      minocycline therapy and able to recognize the characteristic symptoms at an early
      stage.

PMID- 9542867
TI  - [A painful encounter with the weever (Echiichtis vipera)].
AB  - The National Poisons Information Centre of the National Institute of Public
      Health and the Environment in the Netherlands in the past 2 years received dozens
      of requests for information about intoxication due to stings of the weever,
      Echiichtis vipera. The venomous apparatus of the weever consists of gill cover
      spines and 5 to 8 dorsal fin spines. The fish buries itself in the sandy or muddy
      bottom of the sea to wait for prey. The mixture of toxins that enters the skin
      upon contact with the spines causes a heavy local reaction, characterized mostly
      by pain, which untreated persists for 24 hours. An erythematous oedema may
      develop locally, spread over the entire extremity and persist for days. Systemic
      reactions are rare. Since the toxin mixture is heat labile, treatment is
      essentially simple: clean the wound and immerse the affected limb as soon as
      possible in warm water (45 degrees C) for 30 to 90 minutes. This makes the pain
      disappear.

PMID- 9542869
TI  - [An amebic liver abscess; early suspicion, late detection].
AB  - Two men aged 38 and 26 years developed symptoms including pain in the (upper)
      abdomen, malaise and fever 1.5-5 months after visiting the Caribbean. It was only
      after repeated ultrasonography that liver abscesses were observed. Adequate
      treatment was instituted and the patients recovered. The diagnosis of 'amoebic
      abscess of the liver' is usually based on the clinical presentation, the
      serological findings and characteristic observations at ultrasonography. However,
      if patients are seen at an early stage of development of the abscess, the
      serological findings may be negative and the ultrasonographic findings normal;
      consequently these findings do not justify exclusion of the diagnosis.

PMID- 9542870
TI  - [Is the term 'registration' applicable for homeopathic drugs?].

PMID- 9542871
TI  - [Is the term 'registration' applicable for homeopathic drugs?].

PMID- 9542872
TI  - [Is the term 'registration' applicable for homeopathic drugs?].

PMID- 9542873
TI  - [Blue toes and kidney insufficiency].

PMID- 9542874
TI  - [European registration of drugs; consequences for prescriber and patient].

PMID- 9542875
TI  - [Thorn apple poisoning].

PMID- 9542876
TI  - [Barrett esophagus and Barrett carcinoma].

PMID- 9542877
TI  - [A sleeping disorder seldom comes alone].

PMID- 9542878
TI  - [Failing diuretics in severe chronic heart failure].
AB  - Three patients with chronic heart failure, men aged 29, 78 and 69 years,
      developed severe dyspnoea and oedema in spite of reduced sodium and fluid intake
      and medication including furosemide. Heart failure may become 'resistant to
      diuretics' due to pharmacokinetic and pharmacodynamic causes. High-dose
      continuous intravenous administration of a loop diuretic may afford relief in
      such cases, if necessary in combination with a thiazide derivative, an ACE
      inhibitor, an inotropic agent or an extracorporal technique. Monitoring and
      correction of the state of hydration of a patient with chronic heart failure may
      improve the prognosis and the quality of life.

PMID- 9542879
TI  - [Kidney transplantation without previous dialysis: limitations, but also
      possibilities].
AB  - Kidney transplantation guarantees a better quality of life than dialysis and is
      less costly. Transplantation without preceding dialysis is an attractive option.
      However, transplantation long before end-stage renal failure prolongs the period
      of exposure to immunosuppressive therapy, thereby increasing the risk of
      malignancy. Transplantation at one year before dialysis-dependency is expected
      would seem an acceptable compromise. Unfortunately, this option is purely
      theoretical because there is a long waiting-list due to the existing donor
      shortage. Patients are usually put on the waiting-list after dialysis has already
      been started. Extension of the list with pre-dialysis patients is currently only
      justifiable in exceptional cases. These limitations do not apply to patients who
      have received an offer of kidney donation from a living (related or unrelated)
      donor. In these patients transplantation can be done as soon as the creatinine
      clearance has reached a level of 10-12 ml per minute. More attention should be
      paid to this form of transplantation, because it can help to decrease the donor
      shortage.

PMID- 9542880
TI  - [Acute dystonia].
AB  - Acute dystonia is a side effect of antipsychotic medication; it nearly always
      develops a few weeks after the start of a dopamine-blocking agent or substantial
      increase of the dosage. Acute dystonia is characterized as a syndrome of
      sustained muscle contractions, frequently causing twisting and repetitive
      movements or abnormal postures. The risk of acute dystonia depends greatly on the
      presence of risk factors: early age, male sex, use of cocaine, a history of acute
      dystonia, and use of a highly potent antipsychotic agent in a normal dosage. The
      mechanism underlying acute dystonia is unknown: both increase and decrease of the
      striatal dopamine transmission have been put forward as possible causes. Acute
      dystonia may also be caused by dopamine-blocking agents that are used not as
      antipsychotic medication but, for instance, as anti-emetics. Anticholinergic
      agents are extremely efficacious in treatment as well as prevention of acute
      dystonia. Prophylaxis of acute dystonia is indicated for patients belonging to
      the risk groups.

PMID- 9542881
TI  - [Good experiences with an implantable automatic defibrillator with transvenous
      electrodes for patients with life-threatening arrhythmias].
AB  - OBJECTIVE: To describe the results of treatment of patients with a life
      threatening arrhythmia by implantation of an second generation implantable
      cardioverter defibrillator with transvenous electrodes. DESIGN: Descriptive.
      SETTING: St.-Antonius Hospital, Nieuwegein, the Netherlands. METHOD: In the
      period October 1991-February 1996 the ICD with transvenous electrodes was
      implanted in 44 patients. After a year the quality of life was assessed by
      written questionnaire. RESULTS: The in-hospital mortality was 1/44 (2%), without
      peroperative death. During follow-up 4 patients died: 3 due to congestive heart
      failure and 1 due to sudden cardiac death. Within one year 50% of the patients
      had a therapeutical ICD discharge. In 30/44 (68%) patients antiarrhythmic drugs
      were prescribed to reduce the number of ICD discharges or because they were
      suffering from paroxysmal atrial fibrillation with high heart rates, which could
      result in an inappropriate ICD discharge. Quality of life analysis showed a good
      acceptance of the ICD, although 86% of the patients considered it a very serious
      limitation that they were not allowed to drive a motor vehicle anymore.
      CONCLUSION: The ICD constitutes a major step forward in the treatment of life
      threatening ventricular arrhythmias because the implantation is easier and follow
      up shows adequate antiarrhythmic effects and survival.

PMID- 9542882
TI  - [Initial Groningen experiences with dynamic cardiomyoplasty].
AB  - Four patients, one woman and three men aged 48, 62, 49, en 54 years respectively,
      were subjected to cardiomyoplasty because of medically refractory heart failure
      secondary to ischaemic or idiopathic dilating cardiomyopathy. The operation and
      the training period were uncomplicated. In one patient symptoms of heart failure
      did not improve; the other patients experienced substantial relief of symptoms.
      However, all three died suddenly within one year after the operation, probably
      due to ventricular arrhythmias. Cardiomyoplasty may deserve a place in the
      treatment of heart failure, provided sudden death can be better prevented.
      Possibly, treatment with an implantable cardioverter-defibrillator might be
      useful.

PMID- 9542883
TI  - [Suppurative hidradenitis].
AB  - An obese woman aged 18 years had been suffering for several years from axillary
      hidradenitis suppurativa. Repeated incision and drainage never gave lasting
      results and the patient became socially isolated. Hidradenitis suppurativa is a
      chronic suppurative inflammation of skin areas containing apocrine glands: the
      skin of the axillae, of the breasts and of the anogenital region. Treatment in
      the first instance consists of general hygienic measures. Pharmaceuticals used
      include antibiotics, antiandrogens and oestrogens. Surgery is performed when the
      condition is at an advanced stage, with cellulitis and scarring; ample excision
      is necessary to reduce the risk of recurrence. CO2 laser therapy is a new method
      of treatment that shows good results in incipient and advanced lesions.

PMID- 9542884
TI  - [History of healing; bath treatment as psychiatric therapy (1900-1950)].
AB  - During the first decade of the twentieth century the prolonged bath treatment was
      introduced as a therapy for restless patients in Dutch psychiatric institutions.
      They were kept for hours or days at a stretch in lukewarm water, in order to calm
      them down. It became a common treatment, which nevertheless was gradually
      replaced by occupational therapy. The rise of psychopharmacology during the
      fifties of this century marked the end of the prolonged bath treatment.

PMID- 9542885
TI  - [The changed role of chemotherapy in the treatment of stage III non-small-cell
      lung carcinoma].

PMID- 9542886
TI  - [The changed role of chemotherapy in the treatment of stage III non-small-cell
      lung carcinoma].

PMID- 9542887
TI  - [The changed role of chemotherapy in the treatment of stage III non-small-cell
      lung carcinoma].

PMID- 9542888
TI  - [A uniform protocol for liver transplantation in adults in The Netherlands].

PMID- 9542889
TI  - Consciousness and neuroscience.

PMID- 9542890
TI  - EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and
      gabaergic neurons besides pyramidal cells in the rat cerebral cortex.
AB  - High-affinity uptake of glutamate from the synaptic cleft plays a crucial role in
      regulating neuronal activity in physiological and pathological conditions. We
      have used affinity-purified specific polyclonal antibodies raised against a
      synthetic peptide corresponding to the C-terminal region of rabbit and rat EAAC1,
      a glutamate (Glu) transporter believed to be exclusively neuronal, to investigate
      its cellular and subcellular localization and whether it is expressed exclusively
      in glutamatergic cells of infragranular layers, as suggested by previous studies.
      Light microscopic studies revealed that EAAC1 immunoreactivity (ir) is localized
      to neurons and punctate elements in the neuropil. EAAC1-positive neurons were
      more numerous in layers II-III and V-VI, i.e. throughout all projection layers.
      Most EAAC1-positive neurons were pyramidal, although nonpyramidal cells were also
      observed. Some EAAC1-positive non-pyramidal neurons stained positively with an
      antiserum to GAD, thus demonstrating that EAAC1 is not confined to glutamatergic
      neurons. Non-neuronal EAAC1-positive cells were also observed in the white
      matter, and some of them stained positively with an antiserum to GFAP.
      Ultrastructural studies showed that EAAC1-ir was in neuronal cell bodies,
      dendrites and dendritic spines, but not in axon terminals, i.e. exclusively
      postsynaptic. Analysis of the type of axon terminals synapsing on EAAC1-ir
      profiles showed that 97% of them formed asymmetric contacts, thus indicating that
      EAAC1 is located at the very sites of excitatory amino acid release.
      Unexpectedly, EAAC1-ir was also found in a few astrocytic processes located in
      both the gray and the white matter. The localization of EAAC1 may explain the
      pathological symptoms that follow EAAC knockout (seizures and mild toxicity), as
      seizures could be due to the loss of EAAC1-mediated fine regulation of neuronal
      excitability at axodendritic and axospinous synapses, whereas the mild toxicity
      may be related to the functional inactivation of astrocytic EAAC1.

PMID- 9542891
TI  - A profile of cortical gray matter volume deficits characteristic of
      schizophrenia.
AB  - Quantitative magnetic resonance imaging (MRI) studies from our laboratory have
      reported that patients with schizophrenia show a widespread cortical gray matter
      volume deficit, which is especially pronounced in the prefrontal and anterior
      superior temporal cortices. The present study compared two separate samples of
      schizophrenic patients -- 71 men from a Veterans Administration (VA) hospital and
      a sample of 57 severely ill men from a state hospital (SH) -- in an effort to
      test whether the pattern of brain volume abnormalities previously observed in VA
      schizophrenic patients can be generalized to other groups of schizophrenic
      patients. MRI-derived brain volumes of gray matter, white matter and sulcal
      cerebrospinal fluid (CSF) in six cortical regions, and CSF in the lateral and
      third ventricles were computed. All MRI volumes were adjusted for normal
      variation in head size and age and were expressed as standardized Z-scores, which
      also permitted structures of different sizes to be compared directly. The two
      schizophrenic groups displayed similar patterns of volume abnormalities: cortical
      gray matter but not white matter volume deficits that were widespread but
      especially notable in the prefrontal and temporal regions. The regional gray
      matter deficits in the SH group were generally greater than those in the VA
      group, particularly in the prefrontal and posterior superior temporal regions.
      Both schizophrenic groups had abnormally large volumes of the cortical sulci and
      lateral and third ventricles; however, the SH group showed greater enlargements,
      the most prominent occurring in the ventricles and temporal sulci. The
      overlapping patterns of cortical gray matter deficits in the two groups provide
      evidence for generality of this pattern of regional brain volume abnormalities in
      schizophrenia.

PMID- 9542892
TI  - The posterior field P of cat auditory cortex: coding of envelope transients.
AB  - The posterior field (P) of the cat auditory cortex contains a very high
      proportion of neurons whose responses change non-monotonically with the sound
      pressure level (SPL) of tonal stimuli, leading to circumscribed frequency-SPL
      response areas, and it has therefore been suggested that field P may be
      specialized for processing of sound intensity. We demonstrate here a great
      diversity of response areas in field P. Furthermore, by varying tone SPL and rise
      time, we show that, as in primary auditory cortex (AI), the onset response of a
      field P neuron is better described as a function of the instantaneous peak
      pressure (envelope) at the time of response generation than of the steady-state
      SPL of the stimulus. Such responses could be used to track transients or
      represent envelopes in more general terms, rather than to code SPL. Compared with
      AI, field P neurons have relatively long minimum latencies along with a large
      jitter in spike timing. Tracking would therefore be most effective for slowly
      varying envelopes, and one function of the inhibition that generates non
      monotonicity in field P may be to suppress temporally sluggish responses to rapid
      transients, such as the onsets of high-SPL, short rise time tones. Field P may
      thus be specialized for coding slowly varying signals.

PMID- 9542893
TI  - Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic
      deficits and reduces dendritic branching and spine density of neocortical
      pyramidal neurons.
AB  - The role of basal forebrain-derived cholinergic afferents in the development of
      neocortex was studied in postnatal rats. Newborn rat pups received
      intraventricular injections of 192 IgG-saporin. Following survival periods
      ranging from 2 days to 6 months, the brains were processed to document the
      cholinergic lesion and to examine morphological consequences. Immunocytochemistry
      for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA
      demonstrate a loss of approximately 75% of the cholinergic neurons in the medial
      septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ
      hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal
      forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a
      marked reduction of the cholinergic axons in neocortex. Cholinergic axons are
      reduced throughout the cortical layers; this reduction is more marked in medial
      than in lateral cortical areas. The thickness of neocortex is reduced by
      approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal
      cells reveals a reduction in cell body size and also a reduction in numbers of
      branches of apical dendrites. Spine densities on apical dendrites are reduced by
      approximately 20-25% in 192 IgG-saporin-treated cases; no change was detected in
      number of spines on basal dendrites. These results indicate a developmental or
      maintenance role for cholinergic afferents to cerebral cortical neurons.

PMID- 9542894
TI  - Auditory cortical responses in hearing subjects and unilateral deaf patients as
      detected by functional magnetic resonance imaging.
AB  - Functional magnetic resonance imaging is a non-invasive method for the detection
      of focal brain activity at high spatial resolution. Acoustic stimulation leads to
      a blood oxygenation level dependent signal change in the plane of the superior
      temporal gyrus. The dependence of this response in the auditory cortex on
      binaural, monaural left and monaural right acoustic stimulation for 10 healthy
      subjects and five monaural deaf patients is described. Acoustic stimulation
      consists of 1000 Hz pulsed sine tones at a pulse rate of 6 Hz and a sound
      pressure level of 95 dB. For monaural stimulation, normal-hearing subjects
      revealed a strong lateralization of cortical response towards the contralateral
      hemisphere. The lateralization ratios between left and right hemispheric response
      areas were 3.4-5.2 for monaural stimulation and nearly balanced for binaural
      stimulation. Additionally, the sum of cortical activation volumes induced by
      monaural left and right stimulation was approximately 30% smaller than for
      binaural stimulation, indicating either inhibitory mechanisms or neuronal
      facilitation within the auditory pathways. For monaural deaf subjects the
      lateralization ratio between left to right response was just 1.3 towards the
      contralateral hemisphere of the healthy ear, which is comparable to binaural
      responses of normal-hearing subjects. This observation seems to indicate a
      plasticity or a reorganization of auditory pathways of monaural deaf patients.

PMID- 9542895
TI  - Age-related differences in distractibility and response to methylphenidate in
      monkeys.
AB  - Increased susceptibility to distraction is a symptom of normal aging and several
      clinical syndromes, including Alzheimer's disease and attention deficit
      disorders. In the present study, aged and young adult macaques were well-trained
      to perform an automated delayed matching-to-sample (DMTS) task which assesses
      both attention and short-term memory. On 19% of all trials, a task-relevant
      distracting stimulus was presented during either the initial 1 or 3 s of delay
      intervals (early onset) or the final 1 or 3 s of delay intervals (late onset). In
      aged monkeys, both early and late onset distractors lasting 1 or 3 s impaired
      delayed recall on trials with the shortest delay intervals, but did not affect
      accuracy on trials with long delay intervals. In contrast, young adult monkeys
      were impaired only by the presence of an early onset distractor lasting 3 s.
      Impairment was selective for only those trials with the shortest delay intervals.
      Late onset distractors were relatively ineffective in producing distractibility
      in young adult animals. Methylphenidate (MPH; 0.005-1.0 mg/kg) failed to reduce
      distractibility in aged monkeys, producing locomotor abnormalities and hypophagia
      at doses ranging from 0.25 to 1.0 mg/kg. In young adult monkeys, however,
      distractibility was significantly attenuated by administration of the 0.125 mg/kg
      dose. Habituation to the distracting stimulus (under saline conditions) was
      assessed throughout the study and was not evident at any time point of testing.
      These data indicate that attention and recall after brief delays are impaired
      following exposure to a task-relevant distracting stimulus in both aged and young
      adult monkeys, but that aged monkeys are more susceptible to distraction and do
      not receive significant benefit from MPH administration.

PMID- 9542896
TI  - Optical imaging and electrophysiology of rat barrel cortex. I. Responses to small
      single-vibrissa deflections.
AB  - A study was undertaken to investigate the response of the rodent somatosensory
      barrel cortex to single-whisker, near-threshold vibrissal stimuli. Cortical
      responses to controlled whisker deflections were recorded by (i) conventional
      multi-unit extracellular recording within the cytochrome oxidase rich barrels
      centers and the interbarrel septa, and (ii) intrinsic signal optical imaging, a
      technique that provides a spatial view of cortical activation thought to be
      related to the deoxygenation of hemoglobin in activated areas. Barrel cortex
      neurons responded weakly to whisker deflections of 0.04 degrees. Their response
      to a series of small stimuli of increasing amplitude was well-fitted by a
      logarithmic function. Responses to larger stimuli declined monotonically with
      distance from the center of the barrel column, and were characterized by greater
      onset and offset firing rates, by greater post-excitatory reduction of firing to
      below spontaneous levels, and by shorter response latency. In comparison to
      measurements taken previously from primary vibrissal afferent fibers, we conclude
      that cortical cells can respond to activity in a very small fraction of first
      order sensory neurons.

PMID- 9542897
TI  - Optical imaging and electrophysiology of rat barrel cortex. II. Responses to
      paired-vibrissa deflections.
AB  - A study was undertaken to investigate the response of the rodent somatosensory
      barrel cortex to paired-whisker stimuli. Cortical responses to controlled whisker
      deflections were recorded by (i) conventional multi-unit extracellular recording
      within the cytochrome oxidase rich barrels centers, and (ii) intrinsic signal
      optical imaging, a technique that measures an optical correlate of neuronal
      activity thought to be related to the deoxygenation of hemoglobin in activated
      regions. Stimuli were applied to two whiskers in sequence, at temporal
      separations ranging from 0 to 60 ms. Over intervals of 10-40 ms, the primary
      effect of paired-whisker stimulation was suppressive. We suggest that paired
      whisker inhibition results from the activation of layer IV fast-spike units
      within the principle whisker's barrel, by excitatory input arriving from a
      surround-whisker. Paired-whisker stimulation produces inhibition in intrinsic
      images, because it results in a net reduction in layer II/III and/or layer IV
      metabolism. Intra-cortical inhibition may serve to convert the sequence of inputs
      from the whisker array into a barrel cortex magnitude code that can be read by
      higher cortical areas.

PMID- 9542898
TI  - Enzyme-linked immunosorbent assay using recombinant OspC and the internal 14-kDa
      flagellin fragment for serodiagnosis of early Lyme disease.
AB  - The outer surface protein C (OspC) and the internal 14-kDa flagellin fragment of
      strain GeHo of Borrelia burgdorferi sensu stricto were expressed as recombinant
      proteins in Escherichia coli and were purified for use in an immunoglobulin M
      (IgM) enzyme-linked immunosorbent assay (OspC-14-kDa antigen ELISA). No hint at
      disturbing protein-protein interferences, which might influence the availability
      of immunoreactive epitopes, was found when the recombinant antigens were combined
      in the ELISA. The recombinant OspC-14-kDa antigen ELISA was compared to a
      commercial IgM ELISA that used a detergent cell extract from Borrelia afzelii PKo
      as the antigen. According to the manufacturer's information, the cell extract
      contains, in addition to other antigens, the following diagnostically relevant
      antigens: the 100-kDa (synonyms, 93- and 83-kDa antigens), 41-kDa, OspA, OspC,
      and 17-kDa antigens. The specificity was adjusted to 95% on the basis of data for
      154 healthy controls. On testing of 104 serum samples from patients with erythema
      migrans (EM), the sensitivity of the recombinant ELISA (46%) for IgM antibodies
      was similar to that of the commercial ELISA (45%). However, when 42 serum samples
      from patients with polyclonal B-cell stimulation due to an Epstein-Barr virus
      infection were tested, false-positive reactions were significantly less frequent
      in the recombinant ELISA (10%) than in the whole-cell-extract ELISA (23%). OspC
      displays sequence heterogeneity of up to 40% according to the genomospecies.
      However, when the reactions of serum specimens from controls and EM patients with
      OspC from representative strains of B. burgdorferi sensu stricto (strain GeHo)
      and B. afzelii (strain PKo) were compared in an ELISA, almost no differences in
      specificity and sensitivity were seen. This demonstrates that the sera
      predominantly recognize the common epitopes of OspC tested in this study. In
      conclusion, we suggest that the OspC-14-kDa antigens ELISA is a suitable test for
      the detection of an IgM response in early Lyme disease.

PMID- 9542899
TI  - Multicenter evaluation of the COBAS AMPLICOR HCV assay, an integrated PCR system
      for rapid detection of hepatitis C virus RNA in the diagnostic laboratory.
AB  - The benefits shown by the recent introduction of PCR for the in vitro diagnosis
      of hepatitis C virus (HCV) infection has prompted the development of
      standardized, ready-to-use assays that can be implemented in routine clinical
      laboratories. We have evaluated the clinical performance of COBAS AMPLICOR HCV
      (COBAS), the first instrument system that allows the automation of HCV RNA
      amplification and detection, to determine its performance in the routine
      laboratory setting. More than 2,000 specimens collected at five centers were
      analyzed in parallel by the COBAS and the manual AMPLICOR HCV (AMPLICOR) tests,
      and the results were compared with the results for biochemical and serological
      markers of HCV. In this study the two PCR systems showed the same accuracy, with
      a concordance rate of 99.8%. As expected, the correlation between serology and
      PCR was not absolute because the presence of anti-HCV antibodies may be
      associated with a latent or past infection. On the other hand, if the presence of
      confirmed anti-HCV antibodies and elevated alanine aminotransferase levels are
      taken as the "gold standard," indicating an active, ongoing infection, the COBAS
      and AMPLICOR tests show high and comparable sensitivities (100%) and
      specificities (98%), with positive and negative predictive values of 100 and 97%,
      respectively. During the study no false-positive reactions were detected. The use
      of an internal control allowed the identification of inhibitory substances that
      prevented amplification for 0.3 and 0.4% of samples tested by the COBAS and
      AMPLICOR tests, respectively. Compared to the manual system, the COBAS system
      allowed a significant reduction of hands-on time and could improve the overall
      laboratory work flow. In conclusion, these results support the use of the COBAS
      and AMPLICOR tests for the molecular diagnosis of active HCV infections.

PMID- 9542901
TI  - Different hepatitis C virus (HCV) RNA load profiles following seroconversion
      among injecting drug users without correlation with HCV genotype and serum
      alanine aminotransferase levels.
AB  - Hepatitis C virus (HCV) infection often persists in association with chronic
      hepatitis. Different factors have been proposed to determine the clinical outcome
      of HCV infection. The aim of this study was to examine three different factors of
      HCV infection among injecting drug users. Nineteen untreated HCV seroconverters
      were tested longitudinally for the presence of HCV RNA by reverse transcriptase
      (RT) PCR, and results were quantified by the branched-DNA (bDNA) assay. HCV
      genotypes were determined with the first sample taken after HCV seroconversion.
      To assess the natural course of infection, serum alanine aminotransferase (ALT)
      levels were measured at three stages in every individual. The concordance between
      bDNA and RT-PCR was 98.9%. Three distinct patterns were found, according to the
      HCV RNA load after seroconversion during a mean follow-up period of 5 years
      (range, 1 to 8 years). HCV genotype 1a was predominant (52.6%). There was a
      significant increase in serum ALT levels (mean 55.5 U/liter) in the early phase
      of HCV infection, compared with basal serum ALT levels before HCV seroconversion
      and at the end of the follow-up period. Three distinct HCV RNA load profiles were
      found, without apparent relationship to genotype and serum ALT levels in the
      first 5 years of HCV infection.

PMID- 9542900
TI  - Molecular identification of Gemella species from three patients with
      endocarditis.
AB  - Gemella morbillorum and Gemella haemolysans are opportunistic pathogens which
      cause endocarditis and other severe infections. We report on three patients with
      endocarditis, one with endocarditis caused by G. haemolysans and two with
      endocarditis caused by G. morbillorum. The paucity of reports concerning these
      bacteria is probably related to the difficulties associated with their
      identification. For example, one of the strains reported in this study was
      originally sent to our laboratory with a preliminary characterization as a short
      "gram-negative" coccobacillus, highlighting the specific problem associated with
      Gram staining of these bacteria. The usefulness of 16S rRNA gene amplification,
      partial sequencing, and comparison of the nucleotide sequence to those in
      databases when standard phenotypic identification schemes are not helpful is
      emphasized. We also suggest that the use of simple tests, such as testing
      susceptibility to vancomycin for gram-negative bacteria and colistin for gram
      positive bacteria, could prevent misinterpretation of Gram staining in gram
      variable bacteria such as Gemella spp.

PMID- 9542902
TI  - Isolation and characterization of verocytotoxin-producing Escherichia coli O157
      strains from Dutch cattle and sheep.
AB  - In the periods from July to November 1995 and 1996, fecal samples from Dutch
      cattle and sheep were collected at the main slaughterhouses of The Netherlands,
      located at different geographic sites. The samples were examined for the presence
      of verocytotoxin (VT)-producing Escherichia coli (VTEC) of serogroup 0157. E.
      coli O157 strains could be isolated from 57 (10.6%) of 540 adult cattle, 2 (0.5%)
      of 397 veal calves, 2 (3.8%) of 52 ewes, and 2 (4.1%) of 49 lambs. Immunomagnetic
      separation with O157-specific-antibody-coated beads appeared to be significantly
      more sensitive than conventional plating for detection of the organism in feces.
      With the exception of two isolates from adult cattle which appeared to be
      negative for VT genes, all animal isolates were positive for both VT (VT1 and/or
      VT2) and E. coli attaching-and-effacing gene sequences, and therefore, they were
      regarded as potential human pathogens. Although genomic typing by pulsed-field
      gel electrophoresis revealed a wide variety of distinct restriction patterns,
      comparison of the 63 animal isolates with 33 fecal O157 VTEC strains previously
      isolated from humans with the diarrhea-associated form of the hemolytic-uremic
      syndrome by their phage types and VT genotypes showed a marked similarity between
      animal and human isolates: 30 (90.9%) of the 33 human isolates appeared to be of
      E. coli O157 strain types also isolated from cattle and sheep. It was concluded
      that Dutch cattle and sheep are an important reservoir of E. coli O157 strains
      that are potentially pathogenic for humans.

PMID- 9542903
TI  - Comparison of RapID yeast plus system with API 20C system for identification of
      common, new, and emerging yeast pathogens.
AB  - The ability to identify yeast isolates by the new enzymatic RapID Yeast Plus
      System was compared to the ability to identify yeast isolates by the API 20C
      system. A total of 447 yeast isolates representing Blastoschizomyces capitatus,
      17 Candida spp., 5 Cryptococcus spp., Geotrichum spp., 2 Hanseniaspora spp.,
      Hansenula anomala, Hansenula wingei, 3 Rhodotorula spp., Saccharomyces
      cerevisiae, Sporobolomyces salmonicolor, Trichosporon beigelii, and 2 Prototheca
      spp. were evaluated. Also, five quality control strains (Candida spp. and
      Cryptococcus laurentii) with well-documented reactivities by the RapID Yeast Plus
      System were used. Each isolate was evaluated by both methods with a 48-h culture
      grown at 30 degrees C on Sabouraud dextrose agar (Emmons modification) by
      following the recommendations of the manufacturers. The RapID Yeast Plus System
      enzymatic reactions were read after 4 h of incubation, and the API 20C
      carbohydrate assimilation identification profiles were obtained after 72 h of
      incubation. There was good (95.7%) agreement between the identifications obtained
      by the two methods with the eight common Candida spp. and with Cryptococcus
      neoformans. The agreement was lower when the emerging Candida spp. and other
      yeast-like pathogens were tested (79.1 and 75.2%, respectively). These
      preliminary data suggest the potential utility of the RapID Yeast Plus System for
      use in the clinical laboratory for the rapid identification of common yeast
      pathogens as well as certain new and emerging species.

PMID- 9542904
TI  - Taxonomic relationships among spotted fever group rickettsiae as revealed by
      antigenic analysis with monoclonal antibodies.
AB  - The spotted fever group (SFG) is made up of more than 20 different rickettsial
      species and strains. Study of the taxonomic relationships among the group has
      been attempted by phenotypic, genotypic, and phylogenetic analyses. In this
      study, we determined taxonomic relationships among the SFG rickettsiae by
      comparative analysis of immunogenic epitopes reactive against a panel of
      monoclonal antibodies. A total of 98 monoclonal antibodies, which were directed
      against epitopes on the major immunodominant proteins or on the
      lipopolysaccharide-like antigens of strains of Rickettsia africae, Rickettsia
      conorii, Rickettsia massiliae, Rickettsia akari, Rickettsia sibirica, and
      Rickettsia slovaca, were used in the study. The distribution and expression of
      the epitopes among 29 SFG rickettsiae and Rickettsia bellii were assessed by
      determination of reaction titers in a microimmunofluorescence assay. The results
      were scored as numerical taxonomic data, and cluster analysis was used to
      construct a dendrogram. The architecture of this dendrogram was consistent with
      previous taxonomic studies, and the implications of this and other findings are
      discussed.

PMID- 9542905
TI  - Emergence of multidrug resistance in ubiquitous and dominant Pseudomonas
      aeruginosa serogroup O:11. The Greek Pseudomonas Aeruginosa Study Group.
AB  - The serotypes of 88 nonreplicate nosocomial Pseudomonas aeruginosa isolates from
      11 Greek hospitals were studied in relation to their antibiotic susceptibilities.
      Rates of resistance to beta-lactams, aminoglycosides, and quinolones ranged from
      31 to 65%, except for those to ceftazidime (15%) and imipenem (21%). Four
      serotypes were dominant: O:12 (25% of isolates), O:1 (17%), O:11 (16%), and O:6
      (10%). Multidrug resistance rates in the major serogroups O:12 (91%) and O:11
      (79%) were higher than those in serogroups O:1 (40%) and O:6 (43%). Further
      typing with respect to pulsed-field gel electrophoresis patterns following XbaI
      digestion of genomic DNA discriminated the isolates into 74 types. Pulsed-field
      gel electrophoresis revealed that the ubiquitous O:12 group was genetically
      homogeneous, since 95% of strains belonged to two clusters of genotypic
      similarity, while the O:11 strains, present in 8 of the 11 hospitals, were
      distributed among five such clusters. Therefore, apart from the already reported
      O:12 multidrug-resistant European clone, an O:11 population, characterized by a
      serotype known to be dominant in the environment and the hospital in several
      parts of the world, but previously not associated with multidrug resistance to
      antibiotics, has progressed to a multidrug-resistant state.

PMID- 9542906
TI  - Group A streptococcal Vir types are M-protein gene (emm) sequence type specific.
AB  - The M-protein genes (emm genes) of 103 separate impetiginous Streptococcus
      pyogenes isolates were sequenced and the sequence types were compared to the
      types obtained by Vir typing. Vir typing is based on restriction fragment length
      polymorphism (RFLP) analysis of a 4- to 7-kb pathogenicity island encoding emm
      and other virulence genes. By using both HaeIII and HinfI to generate RFLP
      profiles, complete concordance between Vir type and emm sequence type was found.
      Comparison of the emm sequences with those in GenBank revealed new sequence types
      sharing less than 90% identity with known types. Diversity in the emm sequence
      was generated by corrected frameshift mutations, point mutations, and small in
      frame mutations.

PMID- 9542907
TI  - Identification of a novel enteric Helicobacter species in a kitten with severe
      diarrhea.
AB  - A previously undescribed Helicobacter sp. was recovered from a cat with severe
      diarrhea. Based upon the absence of any other identifiable cause of diarrhea,
      this helicobacter may be involved in the development of the disease signs. The
      organism could not be cultured but was described on the basis of 16S rRNA gene
      sequence analysis and morphology and appeared to be a new species, with
      Helicobacter canis being the most genetically similar species. The presence of a
      diarrhea-inducing helicobacter in a companion animal may pose a risk of zoonosis.

PMID- 9542908
TI  - Novel recombinant-antigen enzyme immunoassay for serological diagnosis of
      syphilis.
AB  - Enzyme immunoassay (EIA) is an ideal method for screening large numbers of
      patients for syphilis. We evaluated a novel immune-capture EIA (ICE Syphilis;
      Murex Diagnostics) that uses three recombinant Treponema pallidum antigens
      (TpN15, TpN17, and TpN47) and compared the results with those obtained by the
      native T. pallidum antigen EIA (Captia SelectSyph-G; Centocor) that we currently
      use for the serodiagnosis of syphilis. Specificity was evaluated by screening
      1,184 unselected serum specimens in parallel by the ICE Syphilis and SelectSyph-G
      assays, while sensitivity was tested with a panel of 101 serum specimens
      containing antitreponemal antibodies (treated and untreated) from patients with
      various stages of infection. The specificity of the ICE Syphilis EIA (99.8%) on
      screening was significantly higher (P < 0.02) than that of the SelectSyph-G EIA
      (99.2%). The sensitivity of the ICE Syphilis EIA was significantly higher (P <
      0.01) than that of the SelectSyph-G EIA on both initial (99 versus 91.4%) and
      repeat (100 versus 92.4%) testing. The ICE Syphilis EIA was also significantly
      more sensitive (P < 0.01) than the fluorescent treponemal antibody-abs (92.4%)
      but not the T. pallidum hemagglutination assay (97.1%). Sera containing
      antitreponemal antibodies gave a much higher antibody index (absorbance of test
      serum/kit cutoff) by the ICE Syphilis EIA than by the SelectSyph-G EIA. This
      combined with the overall high sensitivity makes the ICE Syphilis EIA an ideal
      test for excluding or detecting treponemal infection in human immunodeficiency
      virus (HIV)-infected patients. The ICE Syphilis EIA was positive with sera from
      all 15 HIV-infected patients in the study, whereas sera from 3 HIV-infected
      patients were negative by the SelectSyph-G EIA. We conclude that the high
      sensitivity and specificity of the ICE Syphilis EIA and its suitability for
      automation make it an ideal screening test.

PMID- 9542909
TI  - Differentiation of Mycobacterium ulcerans, M. marinum, and M. haemophilum:
      mapping of their relationships to M. tuberculosis by fatty acid profile analysis,
      DNA-DNA hybridization, and 16S rRNA gene sequence analysis.
AB  - Although Mycobacterium ulcerans, M. marinum, and M. haemophilum are closely
      related, their exact taxonomic placements have not been determined. We performed
      gas chromatography of fatty acids and alcohols, as well as DNA-DNA hybridization
      and 16S rRNA gene sequence analysis, to clarify their relationships to each other
      and to M. tuberculosis. M. ulcerans and M. marinum were most closely related to
      one another, and each displayed very strong genetic affinities to M.
      tuberculosis; they are actually the two mycobacterial species outside the M.
      tuberculosis complex most closely related to M. tuberculosis. M. haemophilum was
      more distinct from M. ulcerans and M. marinum, and it appeared to be as related
      to these two species as to M. tuberculosis. These results are important with
      regard to the development of diagnostic and epidemiological tools such as species
      specific DNA probes and PCR assays for M. ulcerans, M. marinum, and M.
      haemophilum. In addition, the finding that M. ulcerans and M. marinum are more
      closely related to M. tuberculosis than are other pathogenic mycobacterial
      species suggests that they may be evaluated as useful models for studying the
      pathogenesis of M. tuberculosis. M. marinum may be particularly useful in this
      regard since strains of this species grow much more rapidly than M. tuberculosis
      and yet can cause systemic disease in immunocompromised hosts.

PMID- 9542910
TI  - Comparative evaluation of FUNGITEST and broth microdilution methods for
      antifungal drug susceptibility testing of Candida species and Cryptococcus
      neoformans.
AB  - The FUNGITEST method (Sanofi Diagnostics Pasteur, Paris, France) is a microplate
      based procedure for the breakpoint testing of six antifungal agents (amphotericin
      B, flucytosine, fluconazole, itraconazole, ketoconazole, and miconazole). We
      compared the FUNGITEST method with a broth microdilution test, performed
      according to National Committee for Clinical Laboratory Standards document M27-A
      guidelines, for determining the in vitro susceptibilities of 180 isolates of
      Candida spp. (50 C. albicans, 50 C. glabrata, 10 C. kefyr, 20 C. krusei, 10 C.
      lusitaniae, 20 C. parapsilosis, and 20 C. tropicalis isolates) and 20 isolates of
      Cryptococcus neoformans. Overall, there was 100% agreement between the methods
      for amphotericin B, 95% agreement for flucytosine, 84% agreement for miconazole,
      83% agreement for itraconazole, 77% agreement for ketoconazole, and 76% agreement
      for fluconazole. The overall agreement between the methods exceeded 80% for all
      species tested with the exception of C. glabrata (71% agreement). The poorest
      agreement between the results for individual agents was seen with C. glabrata
      (38% for fluconazole, 44% for ketoconazole, and 56% for itraconazole) and C.
      tropicalis (50% for miconazole). The FUNGITEST method misclassified as
      susceptible 2 of 12 (16.6%) fluconazole-resistant isolates, 2 of 10 (20%)
      itraconazole-resistant isolates, and 4 of 8 (50%) ketoconazole-resistant isolates
      of several Candida spp. Further development of the FUNGITEST procedure will be
      required before it can be recommended as an alternative method for the
      susceptibility testing of Candida spp. or C. neoformans.

PMID- 9542911
TI  - Use of immunoblot assay to define serum antibody patterns associated with
      Helicobacter pylori infection and with H. pylori-related ulcers.
AB  - Serology has been used worldwide to detect Helicobacter pylori infection. Using
      an immunoblot assay with an antigen from strain ATCC 43579, we sought to
      determine the antibodies which were good markers of colonization and the antibody
      patterns associated with ulcers or atrophy. Out of 98 dyspeptic patients, 41 were
      colonized by H. pylori, based on a positive culture or on positive results of
      both a urease test and direct examination. These 41 patients were seropositive by
      an enzyme immunoassay, and 12 of them had ulcers and 29 had evidence of atrophy.
      Fifty-seven of the 98 patients were noncolonized. Twenty-five of the 57 had
      evidence of gastric atrophy, and 10 were seropositive; 5 of these 10 had ulcers.
      By Western blot analysis, 12 antibodies were significantly more frequent in sera
      from colonized patients, and they produced immunoreactive bands at 125, 87, 74,
      66, 54, 48, 46, 42, 35, 30, 16 and 14 kDa. The presence of at least one band at
      54, 35, or 42 kDa was the best marker of infection (sensitivity, 95%;
      specificity, 82%). In the group of colonized patients, none of the antibody
      patterns were correlated to gastric atrophy. Conversely, the presence of a band
      at 125, 87, or 35 kDa was statistically associated with the presence of an ulcer.
      The simultaneous presence of bands at 87 and 35 kDa predicted the risk of ulcers
      with 83% sensitivity and 69% specificity. By using CagA-positive and VacA
      positive strains and CagA-negative and VacA-negative isogenic mutants, the
      antigens corresponding to the bands at 125 and 87 kDa were shown to be CagA and
      VacA, respectively. On the other hand, the 35-kDa antigen is a novel
      uncharacterized component of H. pylori. These results may help to optimize the
      composition of antigenic preparations for serologic detection of H. pylori
      colonization. Immunoblot assay would be useful for screening patients at high
      risk of ulcers.

PMID- 9542912
TI  - Identification of a new DNA region specific for members of Mycobacterium
      tuberculosis complex.
AB  - The successful use of DNA amplification for the detection of tuberculous
      mycobacteria crucially depends on the choice of the target sequence, which
      ideally should be present in all tuberculous mycobacteria and absent from all
      other bacteria. In the present study we developed a PCR procedure based on the
      intergenic region (IR) separating two genes encoding a recently identified
      mycobacterial two-component system named SenX3-RegX3. The senX3-regX3 IR is
      composed of a novel type of repetitive sequence, called mycobacterial
      interspersed repetitive units (MIRUs). In a survey of 116 Mycobacterium
      tuberculosis strains characterized by different IS6110 restriction fragment
      length polymorphisms, 2 Mycobacterium africanum strains, 3 Mycobacterium bovis
      strains (including 2 BCG strains), and 1 Mycobacterium microti strain, a specific
      PCR fragment was amplified in all cases. This collection included M. tuberculosis
      strains that lack IS6110 or mtp40, two target sequences that have previously been
      used for the detection of M. tuberculosis. No PCR fragment was amplified when DNA
      from other organisms was used, giving a sensitivity of 100% and a specificity of
      100% in the confidence limit of this study. The numbers of MIRUs were found to
      vary among strains, resulting in six different groups of strains on the basis of
      the size of the amplified PCR fragment. However, the vast majority of the strains
      (approximately 90%) fell within the same group, containing two 77-bp MIRUs
      followed by one 53-bp MIRU.

PMID- 9542914
TI  - Identification and purification of specific Penicillium marneffei antigens and
      their recognition by human immune sera.
AB  - Disseminated infection with the dimorphic pathogenic fungus Penicillium marneffei
      is increasingly seen among patients with AIDS in southeast Asian countries.
      Previous studies have demonstrated the presence of humoral immune responses to
      this fungus in patient sera; we have confirmed this work using sera from P.
      marneffei-infected patients (n = 21) to develop Western blots of P. marneffei
      cytoplasmic yeast antigen (CYA). P. marneffei CYA was then partially purified by
      liquid isoelectric focusing, and fractions were subjected to sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting.
      Immunoenzyme development of the Western blots with pooled sera from patients with
      P. marneffei infection and with pooled sera from patients with aspergillosis (n =
      20), candidiasis (n = 10), cryptococcosis (n = 9), and histoplasmosis (n = 11)
      revealed three antigens with relative molecular masses of 61, 54, and 50 kDa.
      These antigens were specifically recognized by the pooled sera from the P.
      marneffei-infected patients. The 61- and 54-kDa antigens were subsequently
      purified to homogeneity by preparative gel electrophoresis, and the 50-kDa
      antigen was partially purified by the same technique. N-terminal amino acid
      sequencing revealed that the 61-kDa antigen had a strong homology (87% identity)
      with the antioxidant enzyme catalase. The three antigens were then subjected to
      SDS-PAGE and Western blotting and to immunoenzyme development with individual
      patient sera; sera from 86% of P. marneffei-infected patients recognized the 61
      kDa antigen, sera from 71% recognized the 54-kDa antigen, and sera from 48%
      recognized the 50-kDa antigen. These specifically recognized antigens are the
      first to be purified from P. marneffei and can be used either singly or in
      combination to detect antibody responses in a large percentage of individuals
      infected with P. marneffei.

PMID- 9542913
TI  - Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and
      CagA protein expression, cytotoxin production, and associated diseases.
AB  - The vacuolating cytotoxin and the cytotoxin-associated protein, encoded by vacA
      and cagA, respectively, are important virulence determinants of Helicobacter
      pylori. Sixty-five H. pylori strains were isolated from dyspeptic patients (19
      with peptic ulcer disease, 43 with chronic gastritis, and 3 with gastric cancer)
      and studied for differences in the vacA and cagA genes and their relationship to
      VacA and CagA expression, cytotoxin activity, and the clinical outcome of
      infection. By PCR, fifty-four (83.1%) of 65 strains had the vacA signal sequence
      genotype s1 and only 10 (15.4%) had the type s2. After primer modification, the
      vacA middle-region types m1 and m2 were detected in 24 (36.9%) and 41 (63.1%)
      strains, respectively. The combinations s1-m2 (31 [47.7%]) and s1-m1 (23 [35.4%])
      occurred more frequently than s2-m2 (10 [15.4%]) (P = 0.01). No strain with the
      combination s2-m1 was found. All 19 patients with peptic ulcers harbored type s1
      strains, in contrast to 32 (74.4%) of 43 patients with gastritis (P = 0.02). The
      vacA genotype s1 was associated with the presence of cagA (P < 0.0001), VacA
      expression (P < 0.0001), and cytotoxin activity (P = 0.003). The cagA gene was
      detectable in 48 (73.8%) of 65 isolates and present in 16 (84.2%) of 19 ulcer
      patients and 29 (67.4%) of 43 patients with gastritis (P = 0.17). The vacA
      genotypes of German H. pylori isolates are identical to those previously
      reported. H. pylori strains of vacA type s1 are associated with the occurrence of
      peptic ulceration and the presence of cagA, cytotoxin activity, and VacA
      expression.

PMID- 9542915
TI  - Evaluation of Pyloriset Screen, a rapid whole-blood diagnostic test for
      Helicobacter pylori infection.
AB  - Helicobacter pylori infection can be detected by several invasive tests based on
      gastroscopy and by noninvasive methods such as serologic assays. Noninvasive
      tests can be used not only in addition to invasive tests but also by themselves
      to screen for H. pylori infection in patients who are not in urgent need of
      endoscopy. Lately, rapid qualitative serologic tests have been developed. In the
      present study, the accuracy of a novel rapid whole-blood test, Pyloriset Screen,
      detecting immunoglobulin G (IgG) and IgA antibodies against H. pylori was
      evaluated. A total of 207 consecutive adult outpatients referred for upper
      endoscopy were enrolled. Gastric biopsy specimens were taken from the antrum and
      corpus for histologic examination and rapid urease testing. Cultures were
      available for 113 patients. Serum samples collected from all patients were tested
      for H. pylori antibodies by two enzyme immunoassays (EIAs) (Pyloriset EIA and an
      in-house EIA), a rapid latex agglutination test (Pyloriset Dry), and Pyloriset
      Screen. Patients were considered H. pylori positive if helicobacters were seen on
      histologic examination (77 patients) or, if in combination with histologically
      verified (although helicobacter-negative) gastritis, their IgG antibody titers
      were elevated in the two EIAs (five patients). The Pyloriset Screen test had a
      sensitivity of 95%, a specificity of 94%, a positive predictive value of 91%, and
      a negative predictive value of 97%. Among 63 patients under the age of 45 years,
      the Pyloriset Screen test did not miss a single H. pylori diagnosis, and only 1
      patient had a false-positive result. Pyloriset Screen could be used reliably to
      screen for H. pylori infection.

PMID- 9542916
TI  - Flow cytometric determination of ganciclovir susceptibilities of human
      cytomegalovirus clinical isolates.
AB  - A flow cytometric assay has been developed for the measurement of
      susceptibilities to ganciclovir of laboratory strains and clinical isolates of
      human cytomegalovirus (HCMV). The assay uses fluorochrome-labeled monoclonal
      antibodies to HCMV immediate-early and late antigens to identify HCMV-infected
      cells and flow cytometry to detect and quantitate the number of antigen-positive
      cells. By this assay, the 50 and 90% inhibitory concentrations (IC50 and IC90,
      respectively) of ganciclovir for the AD169 strain of HCMV were 1.7 and 9.2
      microM, respectively, and the IC50 for the ganciclovir-resistant D6/3/1
      derivative of the AD169 strain was greater than 12 microM. The ganciclovir
      susceptibilities of 17 HCMV clinical isolates were also determined by flow
      cytometric analysis of the effect of ganciclovir on late-antigen synthesis in
      HCMV-infected cells. The average IC50 of ganciclovir for drug-sensitive HCMV
      clinical isolates was 3.79 microM (+/-2.60). The plaque-reduction assay for these
      clinical isolates yielded an average IC50 of 2.80 microM (+/-1.46). Comparison of
      the results of the flow cytometry assays with those obtained from the plaque
      reduction assays demonstrated acceptable bias and precision. Flow cytometric and
      plaque-reduction analysis of cells infected with ganciclovir-resistant clinical
      isolates failed to show a reduction in the percentage of late-antigen-positive
      cells or PFU, even at 96 microM ganciclovir. The flow cytometric assay for
      determining ganciclovir susceptibility of HCMV is quantitative, and objective,
      and potentially automatable, and its results are reproducible among laboratories.

PMID- 9542917
TI  - Epidemiology of a dominant clonal strain of vancomycin-resistant Enterococcus
      faecium at separate hospitals in Boston, Massachusetts.
AB  - In 1996, the dominant (43%) strain of vancomycin-resistant enterococci (VRE; type
      A) at Massachusetts General Hospital was identified at Brigham and Women's
      Hospital (BWH). To characterize the epidemiology of infection with type A
      isolates of VRE at BWH, we collected demographic and clinical data for all
      patients from whom VRE were isolated from a clinical specimen through September
      1996. The first clinical isolates from all BWH patients from whom VRE were
      isolated were typed by pulsed-field gel electrophoresis of SmaI digests of
      chromosomal DNA. Among patients hospitalized after the first patient at BWH
      infected with a type A isolate of VRE was identified, exposures were compared
      between patients who acquired type A isolates of VRE and those who acquired other
      types of VRE. Isolates from 99 patients identified to have acquired VRE were most
      commonly from blood (n = 27), urine (n = 19), or wounds (n = 19). Three months
      after the index patient arrived at BWH and at a time when > or =12 types of
      strains of VRE were present, type A isolates of VRE became dominant; 39 of 75
      (52%) of the study cohort had acquired type A isolates of VRE. We found no
      association between the acquisition of type A isolates of VRE and transfer from
      another institution or temporal overlap by service, ward, or floor with patients
      known to have acquired type A isolates of VRE. By multivariate analysis, only
      residence in the medical intensive care unit (adjusted odds ratio [OR], 3.2; 95%
      confidence interval [CI], 1.4 to 107) and the receipt of two or more antibiotics
      per patient-day (adjusted OR, 12.2; 95% CI, 1.2 to 9.0) were associated with the
      acquisition of strain A. This strain of VRE, dominant at two Boston hospitals,
      was associated with intensity of antibiotic exposures (i.e., two or more
      antibiotics per patient-day). We hypothesize that this strain may have
      unidentified properties providing a mechanism favoring its spread and dominance
      over other extant isolates, and further studies are needed to define these
      properties.

PMID- 9542918
TI  - Epidemiological analysis of Salmonella enteritidis isolates from humans and
      broiler chickens in Thailand by phage typing and pulsed-field gel
      electrophoresis.
AB  - To determine the phage types (PT) of Salmonella enteritidis found in Thailand and
      to clarify the potential for human infection by S. enteritidis in broiler chicken
      meat, human and poultry isolates taken from Thailand between 1990 and 1997 were
      phage typed and analyzed by pulsed-field gel electrophoresis (PFGE). Ten
      different PT were found among the 302 isolates phage typed, with PT 4 being the
      most frequent in human (73.9%) and poultry (76.2%) isolates, followed by PT 1
      (8.0%), 8 (3.6%), and 7a (2.2%) in human isolates and by PT 7a (4.9%), 1 (3.7%),
      and 12 (2.4%) in poultry isolates. Of the 53 isolates analyzed by PFGE, 45 showed
      an indistinguishable pattern (pattern A) by BlnI-digested PFGE and the other 8
      isolates showed a very similar pattern that differed by only a few bands. These
      results indicate the spread of a genetically identical clone of S. enteritidis in
      humans and poultry in Thailand.

PMID- 9542919
TI  - Detection of Mycobacterium tuberculosis complex in sputum specimens by the
      automated Roche Cobas Amplicor Mycobacterium Tuberculosis Test.
AB  - Three hundred twenty-four sputum specimens from 151 patients with suspected
      active pulmonary tuberculosis were tested for the presence of the Mycobacterium
      tuberculosis complex with auramine fluorochrome stain and automated PCR assay
      (Roche Cobas Amplicor Mycobacterium Tuberculosis Test [MTB]). The results were
      compared with those of the conventional Lowenstein-Jensen tube culture and the
      BACTEC radiometer liquid culture. A total of 76 specimens from 32 patients were
      culture positive for M. tuberculosis. In addition, 37 specimens from 15 patients
      were smear and culture positive for other Mycobacterium species but negative by
      the present nucleic acid amplification method and thus were not included in the
      comparison. Compared with culture, the sensitivities, specificities, and positive
      and negative predictive values for acid-fast smear were 67, 98, 93, and 91% and
      those for the Cobas Amplicor MTB were 83, 99, 97, and 95%, respectively. When
      three consecutive sputum specimens per patient could be obtained, the sensitivity
      of the Cobas Amplicor MTB improved to 91%, whereas the sensitivity of the acid
      fast smear remained unchanged.

PMID- 9542920
TI  - Performance of a PCR assay for detection of Pneumocystis carinii from respiratory
      specimens.
AB  - This study evaluates the performance of a PCR assay for the detection of
      Pneumocystis carinii from respiratory specimens that has been designed for use in
      the clinical microbiology laboratory. The test includes a simple method for
      nucleic acid extraction and amplification, a colorimetric probe hybridization
      technique for detection of amplicons, and an internal control to evaluate for the
      presence of inhibitors of amplification. Two hundred thirty-two clinical
      specimens (120 induced-sputum [IS] and 112 bronchoalveolar lavage [BAL]
      specimens) from 168 patients were tested by both immunofluorescent (direct
      fluorescent-antibody [DFA]) staining and PCR. Of the 112 BAL specimens, 17 were
      positive for P. carinii by DFA staining and PCR. An additional two specimens were
      DFA negative and PCR positive. For BAL specimens, the sensitivity and specificity
      of PCR compared to DFA were 100 and 98%, respectively. Eighteen IS specimens were
      positive for P. carinii by DFA, and 27 were positive by PCR. One of the 18 DFA
      positive IS specimens was negative by PCR; this patient had just completed
      therapy for P. carinii pneumonia. Of the 10 specimens that were PCR positive and
      DFA negative, 4 were from patients who had a subsequent BAL specimen that was
      positive by DFA and PCR. For IS specimens, the sensitivity of DFA and PCR was 82
      and 95%, respectively. The specificity of PCR for IS specimens was 94%. Due to
      the high sensitivity of PCR for the detection of P. carinii from IS specimens, a
      PCR-based diagnostic test may be a useful screening test and may alleviate the
      need for bronchoscopy in some patients.

PMID- 9542921
TI  - Identification of Lactococcus garvieae by PCR.
AB  - Lactococcus garvieae junior synonym Enterococcus seriolicida) is an emerging
      zoonotic agent isolated from economically important fish (rainbow trout and
      yellowtail), from cattle, and from humans. Clindamycin susceptibility is the only
      phenotypic test which can differentiate L. garvieae from Lactococcus lactis,
      another emerging agent in humans. A PCR assay for the identification of L.
      garvieae was developed and resulted in an amplified fragment of 1,100 bp in size.
      The PCR assay was shown to be specific to L. garvieae. The PCR assay was positive
      for all the L. garvieae strains tested, which originated from three different
      continents (Asia, Australia, and Europe). The PCR assay was negative for the
      phenotypically similar L. lactis and for all the other fish pathogens tested,
      including Streptococcus iniae and Aeromonas salmonicida. The PCR assay was
      applied to plasma obtained from diseased animals and was found sensitive enough
      to detect bacteria from 1 microl of plasma. The PCR assay that was developed is
      the only practical test besides the clindamycin test which can specifically
      identify the zoonotic agent L. garvieae and which can differentiate it from L.
      lactis.

PMID- 9542922
TI  - Soft salt-mannitol agar-cloxacillin test: a highly specific bedside screening
      test for detection of colonization with methicillin-resistant Staphylococcus
      aureus.
AB  - The early detection of colonization with methicillin-resistant Staphylococcus
      aureus (MRSA) of patients in intensive-care units is an essential step in the
      strategy for preventing MRSA epidemics. In this study, tubes containing soft salt
      mannitol agar with cloxacillin (6 microg/ml) (SSMAC) were prepared for
      inoculation of clinical samples at patients' bedsides by personnel of an
      intensive-care unit. A total of 1,914 swabs from different sample sites of 81
      patients were dipped into SSMAC tubes, and after 24 h of incubation (in an
      incubator located near the intensive-care unit), an evident color change was
      considered by the intensive-care-unit personnel to be an MRSA alarm. Sixty-three
      (3.3%) SSMAC tubes were considered positive for MRSA, 1,827 (95.4%) were
      considered negative, and 24 (1.2%) were considered intermediate. Compared with
      values for parallel conventional surveillance cultures for MRSA, excluding tubes
      with intermediate results, the SSMAC test had a sensitivity of 72.7%, a
      specificity of 99.2%, a positive predictive value of 76.2%, and a negative
      predictive value of 99.0%. When intermediate tubes were considered positive, the
      corresponding values were 75.3, 98.2, 63.2, and 99.0%, respectively. The
      sensitivity and specificity values of the test to identify MRSA-colonized
      patients were 89.4 and 100%, respectively. Oropharyngeal and naris specimens were
      the most reliable samples for MRSA detection. False-negative results were
      frequent in bronchial aspirates with low (< 10(3) to 10(6) CFU/ml) MRSA counts.
      False-positive results were mainly due to methicillin-resistant Staphylococcus
      haemolyticus. The SSMAC tube is a useful, rapid, and inexpensive tool for the
      early identification of MRSA-colonized patients and, consequently, for the
      implementation of measures to prevent the spread of MRSA.

PMID- 9542923
TI  - Evaluation of use of a new chromogenic agar in detection of urinary tract
      pathogens.
AB  - CHROMagar Orientation, a new chromogenic medium, was evaluated for the detection
      and differentiation of gram-positive and gram-negative pathogenic microorganisms
      in 900 urine samples from hospitalized patients. Performance characteristics of
      the medium were evaluated in comparison to those of 5% sheep blood and MacConkey
      agars by direct inoculation of the urine samples on the three media. Four gram
      negative and two gram-positive strains as well as one yeast control strain from
      the American Type Culture Collection were used to ensure quality control.
      CHROMagar Orientation succeeded in detecting all the urine pathogens that were
      detected by the reference media, including gram-negative bacilli, staphylococci,
      streptococci, and yeasts. Colony color and morphology on CHROMagar Orientation
      accurately differentiated Escherichia coli, Proteus mirabilis, Proteus vulgaris,
      Pseudomonas aeruginosa, and Acinetobacter spp. Owing to the similarity in the
      pigmentation produced by Klebsiella, Enterobacter, and Citrobacter isolates, the
      medium failed to distinguish among them; however, these isolates were easily
      recognized as coliforms because of their metallic blue coloration. Staphylococci
      were clearly perceptible: S. aureus and S. epidermidis grow in regular-size
      colonies that range from opaque white to yellowish, and S. saprophyticus produces
      opaque pink colonies. All streptococcus strains, including those from groups B
      and C, were detected. They grow as undifferentiated flat dry diffused colonies,
      and additional tests were required for identification. Enterococci were easily
      discriminated by their strong turquoise pigmentation and their typical growth on
      the agar's surface. Yeast grow in typical creamy wet convex colonies. The
      accuracy of antibiotic susceptibility determinations according to standard
      methods was also tested by picking isolates directly from CHROMagar Orientation.
      The results showed excellent correlation with those obtained with microorganisms
      picked from reference media. Owing to the ease in differentiating mixed flora on
      CHROMagar Orientation, antimicrobic susceptibility tests were performed directly
      from primary isolates in all cases without the need for subcultures.

PMID- 9542924
TI  - Comparison of PCR and microscopy for detection of Cryptosporidium parvum in human
      fecal specimens: clinical trial.
AB  - PCR technology offers alternatives to conventional diagnosis of Cryptosporidium
      for both clinical and environmental samples. We compared microscopic examination
      by a conventional acid-fast staining procedure with a recently developed PCR test
      that can not only detect Cryptosporidium but is also able to differentiate
      between what appear to be host-adapted genotypes of the parasite. Examinations
      were performed on 511 stool specimens referred for screening on the basis of
      diarrhea. PCR detected a total of 36 positives out of the 511 samples, while
      routine microscopy detected 29 positives. Additional positives detected by PCR
      were eventually confirmed to be positive by microscopy. A total of five samples
      that were positive by routine microscopy at Western Diagnostic Pathology but
      negative by PCR and by microscopy in our laboratory were treated as false
      positives. Microscopy therefore exhibited 83.7% sensitivity and 98.9% specificity
      compared to PCR. PCR was more sensitive and easier to interpret but required more
      hands-on time to perform and was more expensive than microscopy. PCR, however,
      was very adaptable to batch analysis, reducing the costs considerably. Bulk
      buying of reagents and modifications to the procedure would decrease the cost of
      the PCR test even more. An important advantage of the PCR test, its ability to
      directly differentiate between different Cryptosporidium genotypes, will assist
      in determining the source of cryptosporidial outbreaks. Sensitivity, specificity,
      ability to genotype, ease of use, and adaptability to batch testing make PCR a
      useful tool for future diagnosis and studies on the molecular epidemiology of
      Cryptosporidium infections.

PMID- 9542925
TI  - Bordetella parapertussis infection in children: epidemiology, clinical symptoms,
      and molecular characteristics of isolates.
AB  - The clinical trial conducted in Italy to evaluate the efficacy of acellular
      pertussis vaccines provided an opportunity to estimate the frequency of clinical
      infections with Bordetella parapertussis and to compare the clinical
      characteristics of children suffering from Bordetella pertussis illness with
      those of children with B. parapertussis illness. This study dealt with 76 B.
      parapertussis infections diagnosed from a population of 15,601 children
      participating in the follow-up of suspected cases of pertussis. An overall
      incidence of 2.1 cases of laboratory-confirmed parapertussis per 1,000 person
      years was observed. Children affected by B. parapertussis infections showed a
      less severe clinical picture both in the duration of symptoms and in the
      percentage of patients affected, even when compared with vaccinated children with
      pertussis. To characterize the isolated strains, we performed assays for
      susceptibility to erythromycin and sulfamethoxazole-trimethoprim, and we examined
      the genomic DNAs by pulsed-field gel electrophoresis. The results showed a high
      degree of genetic stability among B. parapertussis strains regardless of time of
      collection and geographical distribution.

PMID- 9542926
TI  - Diversity of DNA fingerprints of Mycobacterium tuberculosis isolates in the
      United States.
AB  - To investigate the diversity of IS6110 fingerprints of Mycobacterium tuberculosis
      isolates in the United States and to determine if matching IS6110 fingerprints
      represent recent interstate tuberculosis transmission, we performed restriction
      fragment length polymorphism analysis of M. tuberculosis isolates from 1,326
      patients in three geographically separated states. Seven hundred ninety-five
      different IS6110 fingerprint patterns were generated, and pattern diversity was
      similar in each state. Ninety-six percent of the fingerprint patterns were
      observed in only one state, demonstrating that most IS6110 fingerprint patterns
      are confined to a single geographic location. Of the IS6110 fingerprint patterns
      that were shared by isolates from more than one state, most isolates with 1 to 5
      IS6110 copies were separable by pTBN12 fingerprinting whereas those with > 15
      copies were not. One high-copy-number M. tuberculosis strain had identical IS6110
      and pTBN12 fingerprints and included 57 isolates from three states.
      Epidemiological data demonstrated significant recent transmission of tuberculosis
      within each city but not among the states. This suggests that identical
      fingerprints of isolates from geographically separate locations most likely
      reflect interstate tuberculosis transmission in the past, with subsequent
      intrastate spread of disease. Further evaluation of M. tuberculosis strains that
      cause outbreaks in different geographic locations will provide insight into the
      epidemiological and bacteriological factors that facilitate the spread of
      tuberculosis.

PMID- 9542927
TI  - Utility of major leukocyte subpopulations for monitoring secondary
      cytomegalovirus infections in renal-allograft recipients by PCR.
AB  - The feasibility of the major peripheral blood leukocyte (PBL) subsets for use in
      qualitative and quantitative PCR to monitor secondary cytomegalovirus (CMV)
      infection and ganciclovir therapy was assessed with 188 blood samples derived
      from 40 CMV immunoglobulin G-positive renal-allograft recipients. In pp65 antigen
      positive patients all leukocyte fractions, but only 79.5% of plasma preparations,
      were PCR positive. In pp65 antigen-negative samples from patients after antiviral
      treatment only 7.3% of polymorphonuclear cell (PMNL) samples, but 81.8% of
      peripheral blood mononuclear cells (PBMC), and 10.9% of plasma samples remained
      PCR positive. Similarly, in patients with latent infections only 5.0% of PMNL,
      but 51.7% of PBMC preparations, and 8.0% of plasma samples were PCR positive.
      Regarding patients with active CMV infection, CMV DNA copy numbers in PMNL
      correlated significantly with pp65 antigen-positive cell counts before and after
      onset of ganciclovir therapy. Significant differences in CMV DNA copy numbers in
      PMNL and plasma were observed (i) between patients with symptomatic infection and
      those with asymptomatic infection and (ii) between patients with active infection
      and those with latent infection. In contrast, PBMC harbored equally low CMV DNA
      levels both in patients with active infection and those with latent infections,
      and no decline of CMV DNA load in PBMC was observed during antiviral treatment.
      We conclude that detection of CMV DNA in PMNL, not in PBMC, is associated with
      active infections and is more sensitive than detection of CMV DNA in plasma.
      Negative PCR results for PMNL after antiviral therapy indicate recovery, and
      fewer unwanted positive results occur compared to PBMC and plasma. Therefore,
      purified PMNL should be preferred for analysis by qualitative CMV PCR to avoid
      unwanted positive results. The CMV DNA load in PBMC compared with that in PMNL is
      negligible during active infection, so mixed PBL are sufficient for use in
      quantitative PCR.

PMID- 9542928
TI  - Culture-confirmed reinfection of a person with different strains of Borrelia
      burgdorferi sensu stricto.
AB  - In recent years, the utility of serum-based diagnostic testing for Lyme disease
      has improved substantially; however, recovery by culture of the bacterium from
      skin biopsies of suspected patients is still the only definitive laboratory test.
      Reinfection of patients has been assumed to occur but as yet has not been
      documented by serial isolates from the same person. We present a case of culture
      confirmed reinfection of a patient in Menominee County, Michigan. Borrelia
      burgdorferi was isolated from the skin punch biopsy specimens during each episode
      of erythema migrans (EM) and was subjected to molecular strain typing, genetic
      analysis of two outer surface protein genes, protein profile analysis, and serum
      antibody response testing. Results show that these isolates are distinct strains
      of the bacterium and that the two episodes of EM were caused by independent
      infections. This report describes the documented, culture-confirmed reinfection
      of a human by two different strains of B. burgdorferi.

PMID- 9542929
TI  - Characterization of staphylococci with reduced susceptibilities to vancomycin and
      other glycopeptides.
AB  - During the last several years a series of staphylococcal isolates that
      demonstrated reduced susceptibility to vancomycin or other glycopeptides have
      been reported. We selected 12 isolates of staphylococci for which the vancomycin
      MICs were > or =4 microg/ml or for which the teicoplanin MICs were > or =8
      microg/ml and 24 control strains for which the vancomycin MICs were < or =2
      microg/ml or for which the teicoplanin MICs were < or =4 microg/ml to determine
      the ability of commercial susceptibility testing procedures and vancomycin agar
      screening methods to detect isolates with reduced glycopeptide susceptibility. By
      PCR analysis, none of the isolates with decreased glycopeptide susceptibility
      contained known vancomycin resistance genes. Broth microdilution tests held a
      full 24 h were best at detecting strains with reduced glycopeptide
      susceptibility. Disk diffusion did not differentiate the strains inhibited by 8
      microg of vancomycin per ml from more susceptible isolates. Most of the isolates
      with reduced glycopeptide susceptibility were recognized by MicroScan
      conventional panels and Etest vancomycin strips. Sensititre panels read visually
      were more variable, although with some of the panels MICs of 8 microg/ml were
      noted for these isolates. Vitek results were 4 microg/ml for all strains for
      which the vancomycin MICs were > or =4 microg/ml. Vancomycin MICs on Rapid
      MicroScan panels were not predictive, giving MICs of either < or =2 or > or =16
      microg/ml for these isolates. Commercial brain heart infusion vancomycin agar
      screening plates containing 6 microg of vancomycin per ml consistently
      differentiated those strains inhibited by 8 microg/ml from more susceptible
      strains. Vancomycin-containing media prepared in-house showed occasional growth
      of susceptible strains, Staphylococcus aureus ATCC 29213, and on occasion,
      Enterococcus faecalis ATCC 29212. Thus, strains of staphylococci with reduced
      susceptibility to glycopeptides, such as vancomycin, are best detected in the
      laboratory by nonautomated quantitative tests incubated for a full 24 h.
      Furthermore, it appears that commercial vancomycin agar screening plates can be
      used to detect these isolates.

PMID- 9542931
TI  - Evaluation of four methods for rapid identification of Staphylococcus aureus from
      blood cultures.
AB  - The identification of Staphylococcus aureus directly from blood cultures is
      clinically relevant, but it requires a test that is both rapid and reliable.
      Previously, biochemical, immunological, tube coagulase, and thermostable
      endonuclease methods have shown variable sensitivity and specificity. Testing
      directly from blood culture broth has not been described for the latex kit
      Staphaurex Plus (Murex Diagnostics Ltd.), and the modified conventional tests
      have not been used with the newer, continuously monitored blood culture systems.
      In addition, the commercial RAPIDEC staph kit (bioMerieux Vitek, Inc.) has been
      used to detect S. aureus directly from the Vital blood culture system
      (bioMerieux, Marcy l'Etoile, France), but its performance has not been evaluated
      with other continuously monitored systems. A total of 201 clinical blood cultures
      (BACTEC 9240 culture system; Johnston Laboratories, Inc.) in which a Gram stain
      showed gram-positive cocci resembling staphylococci were evaluated prospectively.
      The Staphaurex Plus kit, the tube coagulase test, the thermostable-endonuclease
      test, and the RAPIDEC staph kit were compared. The sensitivities were 23, 92, 85,
      and 98% and the specificities were 99, 100, 93, and 100%, respectively. The
      RAPIDEC staph kit was the most reliable test, with a diagnostic accuracy
      comparable to that of the best published results for any of the rapid tests.
      However, it was the most expensive of the tests and relatively labor-intensive.
      The tube coagulase test was also sensitive, the simplest to perform, and
      inexpensive.

PMID- 9542930
TI  - Detection and identification of Mycobacterium tuberculosis directly from sputum
      sediments by ligase chain reaction.
AB  - Sputum specimens received for the diagnosis of tuberculosis or other
      mycobacterial infections were tested by a ligase chain reaction (LCR)-based assay
      and acid-fast stain and culture techniques. Results from the LCR assay (Abbott
      LCx Mycobacterium tuberculosis [MTB] Assay) were compared to results from
      standard culture techniques held for 6 weeks. Four hundred ninety-three specimens
      from 205 patients suspected of pulmonary tuberculosis were included in the
      prospective study. Thirty-four (6.9%) of the specimens were culture positive for
      M. tuberculosis, and 13 (38%) of these were also fluorochrome stain positive. LCR
      sensitivities and specificities compared to culture were 74 and 98%,
      respectively. LCR sensitivity was 100% for fluorochrome stain-positive specimens
      and 57% for fluorochrome stain-negative specimens. Nine LCR-negative, culture
      positive specimens were the result of low concentrations of M. tuberculosis. No
      inhibitors were detected in any of these specimens. Of the eight LCR-positive,
      culture-negative specimens, five were from patients with active tuberculosis.
      With these considered culture misses, final LCR sensitivity, specificity,
      positive predictive value, and negative predictive value were 77, 99, 91, and
      98%, respectively. The same performance values for the fluorochrome acid-fast
      bacillus smear were 33, 98, 62, and 94%, respectively. After normal laboratory
      sputum processing, the Abbott LCx MTB Assay can be completed in 6 h. Thus, it is
      possible to have results available within 8 h of specimen submission.

PMID- 9542932
TI  - Intergenic transcribed spacer PCR ribotyping for differentiation of Saccharomyces
      species and interspecific hybrids.
AB  - The taxonomy of the genus Saccharomyces has undergone significant changes
      recently with the use of genotypic rather than phenotypic methods for the
      identification of strains to the species level. The sequence of rRNA genes has
      been utilized for the identification of a variety of fungi to the species level.
      This methodology, applied to species of Saccharomyces, allows unknown
      Saccharomyces isolates to be assigned to the type strains. It was the aim of the
      present study to assess whether typing of the intergenic spacer region by using
      restriction fragment length polymorphisms of PCR products (intergenic transcribed
      spacer PCR [ITS-PCR] ribotyping) could distinguish among type strains of the 10
      accepted species of Saccharomyces and further to assess if this method could
      distinguish strains that were interspecific hybrids. Cellular DNA, isolated after
      the lysis of protoplasts, was amplified by PCR using ITS1 and ITS4 primers,
      purified by liquid chromatography, and digested with restriction endonucleases.
      Ribotyping patterns using the restriction enzymes MaeI and HaeIII could
      distinguish all species of Saccharomyces from each other, as well as from Candida
      glabrata, Candida albicans, and Blastomyces dermatitidis. The only exception to
      this was the inability to distinguish between Saccharomyces bayanus and S.
      pastorianus (S. carlsbergensis). Furthermore, interspecific hybrids resulting
      from the mating of sibling species of Saccharomyces were shown to share the ITS
      PCR ribotyping patterns of both parental species. It should now be possible, by
      this simple PCR-based technique, to accurately identify these strains to the
      species level, thereby allowing an increase in our understanding of the
      characteristics required by these interspecific hybrids for their particular
      ecological niches.

PMID- 9542933
TI  - Evaluation of PCR for diagnosis of melioidosis.
AB  - Previously published PCR-based diagnostic tests for melioidosis were evaluated
      for clinical usefulness. A Burkholderia pseudomallei 16S rRNA-derived primer set
      had a sensitivity approaching 100% for clinical samples from 22 culture-confirmed
      cases of melioidosis and enabled diagnosis of 3 culture-negative cases. However,
      samples from 10 of 30 inpatients from Royal Darwin Hospital with other diagnoses
      were positive by PCR, giving a specificity of 67% and a positive predictive value
      of only 70%. Although there are a number of intriguing possible explanations for
      our results, concerns of inappropriate therapy resulting from a positive result
      by PCR have led us to forgo the advantage of rapid PCR diagnosis for melioidosis
      until a better system is validated.

PMID- 9542934
TI  - Detection of staphylococcal superantigenic toxins by a CD69-specific
      cytofluorimetric assay measuring T-cell activation.
AB  - The presence of staphylococcal superantigenic toxins in the supernatants of
      liquid cultures was detected by an easy and rapid method assessing the activation
      of T lymphocytes by cytofluorimetric measurement of CD69 expression.
      Staphylococcus aureus cells were grown in Eagle's minimum essential medium
      supplemented with 5% heat-inactivated fetal calf serum. Supernatant fluids from
      all S. aureus strains producing superantigen-related toxins, including
      enterotoxins A to E, toxic shock syndrome toxin, and exfoliative toxins A and B,
      induced CD69 expression in a significantly higher number of T cells than a cutoff
      of 2%. This CD69 assay might be used for initial detection of superantigens from
      S. aureus strains isolated in the context of staphylococcal toxemia or related
      chronic human diseases such as atopic dermatitis or Kawasaki syndrome.

PMID- 9542936
TI  - Detection of Mycobacterium tuberculosis complex in cattle by PCR using milk,
      lymph node aspirates, and nasal swabs.
AB  - The PCR technique was applied to the diagnosis of tuberculosis in live cattle,
      and both skin-test-negative and skin-test-positive animals were studied. DNA was
      taken from various sources including specimens of lymph node aspirates, milk, and
      nasal swabs. After slaughter and visual inspection, tissues such as lymph nodes,
      lungs, and udders from tuberculin reactors were tested by the same technique.
      Specific oligonucleotide primers internal to the IS6110 insertion element were
      used to amplify a 580-bp fragment. A 182-bp fragment was obtained by designating
      a nested PCR from the first amplification product. This fragment was cloned and
      sequenced, and after being labeled it was employed in dot blot hybridization. A
      total of 100 cattle were tested, and PCR analysis was performed using nasal swab,
      milk, and lymph node aspirate. Sixty skin-test-positive cows were also tested to
      detect mycobacterial DNA in tissue samples from lymph nodes, lungs, and udders,
      and the infection was confirmed in all of the animals. Using PCR analysis of
      tissue samples from slaughtered animals as a "gold standard" we calculated 100%
      values for sensitivity, specificity, and positive and negative predictive values
      for milk and lymph node aspirate samples. The respective values for nasal swab
      samples were 58, 100, 100, and 28%. The respective values for all of the samples
      were 74, 100, 100, and 35%, while for visual inspection the values were 81, 100,
      100, and 58%, respectively. PCR analysis of specimens of lymph node aspirates,
      milk, and nasal swabs from skin-test-negative animals showed that 52% of these
      skin test results were false negatives. These animals, not being removed from the
      farms, represent a potential source of further infection.

PMID- 9542935
TI  - Sensitivity of fluorochrome microscopy for detection of Mycobacterium
      tuberculosis versus nontuberculous mycobacteria.
AB  - The results for 6,532 consecutive mycobacterial respiratory specimens collected
      from 1,040 patients from 1993 to 1995 in a Texas hospital were studied to
      determine the sensitivity of fluorescence microscopy for detection of
      Mycobacterium tuberculosis and nontuberculous mycobacteria (NTM). Smears were
      positive for acid-fast bacilli (AFB) in 63% (677 of 1,082) of specimens growing
      M. tuberculosis and 56% (638 of 1,148) of specimens growing the four most common
      species of NTM. Smear positivity by species was 58% (446 of 776) for M. avium
      complex, 51% (154 of 300) for rapidly growing mycobacteria (98% were M.
      abscessus), 78% (29 of 37) for M. kansasii, and 26% (9 of 35) for M. gordonae.
      Definite or probable disease by clinical criteria was present in 79% of patients
      with M. avium complex, 93% of patients with rapidly growing mycobacteria, 100% of
      patients with M. kansasii, and 0% of patients with M. gordonae. Patients with M.
      avium complex had a low incidence of AIDS (7%), and approximately 50% of non-AIDS
      patients had upper-lobe cavitary disease and 50% had nodular bronchiectasis. Only
      23 of 6,532 (0.35%) of AFB smears were positive with a negative culture excluding
      patients on therapy for established mycobacterial disease. These studies suggest
      that NTM are as likely as M. tuberculosis to be detected by fluorescent
      microscopy in specimens from patients from areas endemic for NTM lung disease and
      at low risk for AIDS.

PMID- 9542937
TI  - Comparison of culture- and non-culture-based methods for quantification of viral
      load and resistance to antiretroviral drugs in patients given zidovudine
      monotherapy.
AB  - Virological assays for human immunodeficiency virus type 1 load and drug
      resistance can broadly be divided into culture-based and molecular biology-based
      methods. Culture-based methods give a direct measure of infectious virus load and
      phenotypic drug resistance, whereas molecular biology-based methods are indirect,
      assaying nucleic acid levels to determine virus load and point mutations
      associated with drug resistance. We have compared culture-based and non-culture
      based methods for patients enrolled in a placebo-controlled trial of zidovudine
      (the Concorde Trial). Virus loads were assayed by culture of peripheral blood
      mononuclear cells (PBMCs) or quantitative PCR, and drug resistance was assayed in
      culture or in a quantitative, PCR-based point mutation assay. The rates of
      detection of viremia and drug resistance were higher by PCR than by culture for
      this population of subjects. Comparison of the virus loads by the two measures
      showed a good correlation for virus loads in PBMCs but a poor correlation for
      virus loads in plasma. The latter result probably reflected the inaccuracies of
      culture in assaying plasma with the low infectious virus titers seen in the study
      population. The concordance of phenotypic and genotypic drug resistance methods
      was high, with all phenotypically resistant isolates having at least one
      resistance-associated mutation and with no mutations being found in a drug
      sensitive isolate. Genomic resistance scores (weighted sums of levels of
      resistance mutations) showed good correlations with the levels of phenotypic
      resistance, and both resistance measures were observed to increase as the
      duration of exposure to drug increased. Overall, non-culture-based methods were
      shown to correlate well with culture-based methods and offer a low-cost, high
      throughput alternative. However, culture-based methods remain the final arbiters
      of infectious virus load and phenotypic drug resistance and are unlikely to be
      superseded entirely.

PMID- 9542938
TI  - Detection of Norwalk virus and other genogroup 1 human caliciviruses by a
      monoclonal antibody, recombinant-antigen-based immunoglobulin M capture enzyme
      immunoassay.
AB  - Sera obtained from two groups of adult volunteers infected with Norwalk virus
      (NV) and two groups of patients involved in two natural outbreaks were tested for
      NV-reactive immunoglobulin M (IgM) by use of a monoclonal antibody, recombinant
      antigen-based IgM capture enzyme immunoassay (EIA). No NV-reactive IgM was
      detected in the preinoculation sera of 15 volunteers, and 14 of 15 showed NV
      reactive antibodies postinfection with NV. All of the volunteers showed IgG
      seroconversion to NV. In the outbreak studies, all 9 persons in one outbreak and
      19 of 24 in another outbreak had NV-reactive IgM. In the first outbreak, only
      three of nine seroconverted to NV, which was likely due to late collection of
      acute-phase sera. In the second outbreak, 21 of 24 showed IgG seroconversion to
      NV. Sequencing of viruses isolated from five stool samples selected from those in
      the second outbreak showed that they were human calicivirus (HuCV) genogroup 1
      viruses related, but not identical, to NV. In the volunteer studies, NV-reactive
      IgM was first detected 8 days postinoculation. The time of development of NV
      reactive IgM antibodies in natural outbreaks was estimated to be similar to that
      found in the volunteer studies. Sera from three Hawaii virus-infected volunteers,
      four Snow Mountain virus patients, and 80 healthy individuals were negative for
      NV-reactive IgM, indicating test specificity for HuCV genogroup I infections.
      This capture IgM EIA is suitable for diagnosis of NV and other HuCV genogroup I
      infections and is especially useful when sera and fecal samples have not been
      collected early in the course of an outbreak.

PMID- 9542939
TI  - Optimization of specimen-handling procedures for accurate quantitation of levels
      of human immunodeficiency virus RNA in plasma by reverse transcriptase PCR.
AB  - Human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma are currently
      widely used clinically for prognostication and in monitoring antiretroviral
      therapy. Accurate and reproducible results are critical for patient management.
      To determine the effects of specimen collection and handling procedures on
      quantitative measurement of HIV-1 RNA, we compared anticoagulants and sample
      processing times. Whole blood was collected from 20 HIV-1-infected patients in
      EDTA, acid citrate dextrose (ACD), and heparin tubes, aliquoted, and stored at
      room temperature. Plasma was separated from whole-blood aliquots prepared at < or
      =1, 3, 6, 24, and 48 h postcollection and then stored at -70 degrees C until use.
      HIV-1 RNA levels were determined by the AMPLICOR HIV-1 MONITOR assay. Heparinized
      plasma samples, which were pretreated with heparinase prior to analysis, had the
      lowest baseline HIV-1 RNA levels. In the first 6 h, HIV-1 RNA levels decreased by
      10, 20, and 31% in EDTA, ACD, and heparin tubes, respectively. From 6 to 48 h
      postcollection, HIV-1 RNA levels decreased in all anticoagulants, albeit at a
      slower, more consistent rate. Our results indicate that EDTA should be the
      anticoagulant of choice for plasma HIV-1 RNA measurement by reverse transcriptase
      PCR, but ACD tubes are acceptable if the plasma is separated within 6 h of blood
      collection. Caution must be applied in the interpretation of absolute HIV-1 RNA
      copy number values obtained with suboptimal specimen collection and processing
      procedures.

PMID- 9542940
TI  - Immunoglobulin M capture assay for serologic confirmation of early Lyme disease:
      analysis of immune complexes with biotinylated Borrelia burgdorferi sonicate
      enhanced with flagellin peptide epitope.
AB  - We previously reported on the efficacy of the enzyme-linked immunoglobulin M
      capture immune complex (IC) biotinylated antigen assay (EMIBA) for the
      seroconfirmation of early Lyme disease and active infection with Borrelia
      burgdorferi. In earlier work we identified non-cross-reacting epitopes of a
      number of B. burgdorferi proteins, including flagellin. We now report on an
      improvement in the performance of EMIBA with the addition of a biotinylated form
      of a synthetic non-cross-reacting immunodominant flagellin peptide to the
      biotinylated B. burgdorferi B31 sonicate antigen source with the avidin
      biotinylated peroxidase complex detection system used in our recently developed
      indirect IgM-capture immune complex-based assay (EMIBA). As in our previous
      studies, the enzyme-linked immunosorbent assay (ELISA) reactivities of antibodies
      liberated from circulating ICs (by EMIBA) were compared with those of antibodies
      in unprocessed serum (antibodies found free in the serum, thus as an IgM-capture
      ELISA, but not EMIBA, because the antibodies were not liberated from ICs), the
      sample usually used in standard ELISAs and Western blot assays. The addition of
      the flagellin epitope enhanced the ELISA signal obtained with untreated sera from
      many Lyme disease patients but not from healthy controls. In tests with both free
      antibodies and ICs, with or without the addition of the flagellin epitope to the
      sonicate, we found the most advantageous combination was IC as the source of
      antibodies and sonicate plus the flagellin epitope as the antigen. In a blinded
      study of sera obtained from patients with early and later-phase Lyme disease,
      EMIBA with the enhanced antigenic preparation compared favorably with other
      serologic assays, especially for the confirmation of early disease.

PMID- 9542941
TI  - Glycogen assay for diagnosis of female genital Chlamydia trachomatis infection.
AB  - Chlamydia trachomatis can synthesize glycogen at various stages in its
      developmental cycle. The glycogen content of female genital epithelial cells was
      detected by anthrone, and the results were compared with those from PCR. A total
      of 320 cervical samples were examined. Of 92 specimens that were positive by PCR,
      78 were positive and 14 were negative by the glycogen assay. Of 228 specimens
      that were negative by PCR, 220 were negative and 8 were positive by the glycogen
      assay. The sensitivity and specificity of the glycogen assay obtained from these
      data were 84.8% (78 of 92) and 96.5% (220 of 228), respectively. Use of the
      glycogen assay to detect the glycogen content in genital epithelial cells may be
      helpful in the diagnosis of C. trachomatis infection. This is an easy, fast, and
      inexpensive assay and can be done in less-sophisticated labs.

PMID- 9542942
TI  - Molecular typing of Staphylococcus aureus based on PCR restriction fragment
      length polymorphism and DNA sequence analysis of the coagulase gene.
AB  - A typing procedure for Staphylococcus aureus was developed based on improved PCR
      amplification of the coagulase gene and restriction fragment length polymorphism
      (RFLP) analysis of the product. All coagulase-positive staphylococci produced a
      single PCR amplification product of either 875, 660, 603, or 547 bp. Those
      strains of epidemic methicillin-resistant S. aureus 16 (EMRSA-16) studied all
      gave a product of 547 bp. PCR products were digested with AluI and CfoI, and the
      fragments were separated by gel electrophoresis. Ten distinct RFLP patterns were
      found among 85 isolates of methicillin-resistant S. aureus (MRSA) and 10
      propagating strains (PS) of methicillin-sensitive S. aureus (MSSA) examined. RFLP
      patterns 1, 2, and 3 were specific to strains of EMRSA-3, -15, and -16,
      respectively. By contrast, RFLP patterns 4 and 5 were seen with a heterogeneous
      collection of strains, together with drug-resistant forms of S. aureus isolated
      in Europe and four propagating strains used for the international phage set. RFLP
      pattern 6 was given by the Airedale isolate and PS 95. RFLP pattern 7 encompassed
      EMRSA-2 (isolate 331), PS 94, and PS 96. An isolate from Germany gave RFLP
      pattern 8. Eight strains of MSSA gave patterns similar to those of methicillin
      resistant strains (RFLP patterns 3, 4, 5, 6, and 7), but two, PS 42E and PS 71,
      gave unique RFLP patterns 9 and 10, respectively. The coagulase gene PCR products
      for 24 isolates of MRSA and two isolates of MSSA were sequenced for both strands.
      The sequences were aligned, and evolutionary lineages were inferred based on
      pairwise distances between isolates.

PMID- 9542943
TI  - Nested PCR assay for detection of granulocytic ehrlichiae.
AB  - A sensitive and specific nested PCR assay was developed for the detection of
      granulocytic ehrlichiae. The assay amplifies the 16S rRNA gene and was used to
      examine acute-phase EDTA-blood and serum samples obtained from seven humans with
      clinical presentations compatible with human granulocytic ehrlichiosis. Five of
      the seven suspected cases were positive by the PCR assay using DNA extracted from
      whole blood as the template, compared with a serologic assay that identified only
      one positive sample. The PCR assay using DNA extracted from the corresponding
      serum samples as the template identified three positive samples. The sensitivity
      of the assay on human samples was examined, and the limit of detection was shown
      to be fewer than 2 copies of the 16S rRNA gene. The application of the assay to
      nonhuman samples demonstrated products amplified from template DNA extracted from
      Ixodes scapularis ticks collected in Rhode Island and from EDTA-blood specimens
      obtained from white-tailed deer in Maryland. All PCR products were sequenced and
      identified as specific to granulocytic ehrlichiae. A putative variant
      granulocytic ehrlichia 16S rRNA gene sequence was detected among products
      amplified from both the ticks and the deer blood specimens.

PMID- 9542944
TI  - Development of PCR assays for species- and type-specific identification of
      Pasteurella multocida isolates.
AB  - Genomic subtractive hybridization of closely related Pasteurella multocida
      isolates has generated clones useful in distinguishing hemorrhagic septicemia
      causing type B strains from other P. multocida serotypes. Oligonucleotide primers
      designed during the sequencing of these clones have proved valuable in the
      development of PCR assays for rapid species- and type-specific detection of P.
      multocida and of type B:2 in particular. This study demonstrated that the primer
      pair designed from the sequence of the clone 6b (KTT72 and KTSP61) specifically
      amplified a DNA fragment from types B:2, B:5, and B:2,5 P. multocida and that the
      primers KMT1T7 and KMT1SP6 produced an amplification product unique to all P.
      multocida isolates analyzed. It was also shown that PCR amplification performed
      directly on bacterial colonies or cultures represents an extremely rapid,
      sensitive method of P. multocida identification.

PMID- 9542945
TI  - Mycobacterium tuberculosis infection in a green-winged macaw (Ara chloroptera):
      report with public health implications.
AB  - Mycobacterium tuberculosis was isolated from the eyelid, skin, tongue, and lungs
      of a green-winged macaw (Ara chloroptera). Two persons living in the same
      household were culture positive for pulmonary tuberculosis 3 to 4 years before
      tuberculosis was diagnosed in the bird. Although humans have not been shown to
      acquire tuberculosis from birds, an infected bird may be a sentinel for human
      infection.

PMID- 9542946
TI  - Misidentification of unusual Aeromonas species as members of the genus Vibrio: a
      continuing problem.
AB  - Two unusual cases of Aeromonas infection are described, one associated with
      bacteremia (Aeromonas schubertii) and another in which the organism was recovered
      from an infected gall bladder (Aeromonas veronii biotype veronii). These strains
      were initially identified as Vibrio damsela and Vibrio cholerae by the Vitek and
      API 20E systems, respectively. Use of appropriate screening tests and familiarity
      with the newer Aeromonas species could prevent initial misidentifications and
      potential public health consequences.

PMID- 9542947
TI  - Baculovirus expression of the fusion protein gene of bovine respiratory syncytial
      virus and utility of the recombinant protein in a diagnostic enzyme immunoassay.
AB  - The fusion (F) protein of bovine respiratory syncytial virus (BRSV) was expressed
      by using a baculovirus vector. Antigenicity was tested by immunofluorescence
      analysis with F-specific monoclonal and polyclonal antibodies. Antibodies to
      recombinant F protein raised in a rabbit neutralized BRSV and human respiratory
      syncytial virus infectivity when tested in a plaque reduction assay. The
      recombinant F protein was evaluated as a source of antigen in an enzyme-linked
      immunosorbent assay (ELISA), and this ELISA was compared with the virus
      neutralization (VN) test for detecting BRSV antibodies in 10 consecutive serum
      samples from four calves vaccinated with a live modified BRSV vaccine and from
      two nonvaccinated control calves. The ELISA with the baculovirus-expressed F
      protein as an antigen compared favorably with the VN test and is a rapid,
      sensitive, and specific method for detecting serum antibodies to BRSV.

PMID- 9542948
TI  - Sensitivity and specificity of an improved rapid latex agglutination test for
      identification of methicillin-sensitive and -resistant Staphylococcus aureus
      isolates.
AB  - The performance of a second-generation rapid agglutination kit, Slidex Staph Plus
      (SSP; bioMerieux), was compared to those of the Slidex Staph (SS; bioMerieux),
      Staphaurex (SRX; Murex Diagnostics), and BBL Staphyloslide (BBL; Becton
      Dickinson) kits by using 508 clinical isolates composed of 150 methicillin
      sensitive Staphylococcus aureus (MSSA) organisms, 154 methicillin-resistant S.
      aureus (MRSA) organisms, and 204 non-S. aureus Staphylococcus spp. Of the 508
      isolates tested, 75% were fresh clinical isolates, with the remainder taken from
      five different freezer collections. All four agglutination tests had comparable
      sensitivities for MSSA and MRSA. However, the SS kit was significantly less
      specific (93.1%) than the three other tests (P > 0.05, McNemar test). These
      results demonstrate that the new rapid latex agglutination kit, SSP, was more
      specific for the identification of S. aureus than the previous version and
      performed comparably to the SRX and BBL kits.

PMID- 9542949
TI  - Rising levels of human cytomegalovirus (HCMV) antigenemia during initial
      antiviral treatment of solid-organ transplant recipients with primary HCMV
      infection.
AB  - In 7 of 18 solid-organ transplant recipients with primary human cytomegalovirus
      (HCMV) infection, HCMV antigenemia levels were unexpectedly found to rise
      significantly (P = 0.018) during a mean time of 7.3 +/- 3.2 days after initiation
      of specific antiviral treatment, whereas corresponding levels of viremia dropped
      significantly (P = 0.043). Thus, shifting to an alternative antiviral drug based
      solely on increasing antigenemia levels is not justified in this group of
      patients.

PMID- 9542951
TI  - Spoligotyping followed by double-repetitive-element PCR as rapid alternative to
      IS6110 fingerprinting for epidemiological studies of tuberculosis.
AB  - A total of 129 clinical isolates of Mycobacterium tuberculosis representing 91
      patients were typed by a combination of direct-repeat (DR)-based spoligotyping
      and an inter-IS6110-PGRS (polymorphic GC-rich region)-PCR, also designated double
      repetitive-element PCR (DRE-PCR). During the first phase of this investigation,
      72 clinical strains representing 52 patients were initially typed by IS6110
      restriction fragment length polymorphism (RFLP) and DR-RFLP, followed by
      spoligotyping and DRE-PCR. In the second phase of this investigation, the
      discriminating ability of spoligotyping plus DRE-PCR was studied for 57 isolates
      from 39 patients who were suspected to be epidemiologically linked, and the
      typing results were later confirmed by IS6110-RFLP and DR-RFLP analyses. The
      molecular clustering of the isolates remained identical irrespective of the
      methods used. These results show that the association of two PCR-based
      fingerprinting techniques for molecular epidemiology of tuberculosis has a
      discriminating ability similar to the IS6110-RFLP reference method.

PMID- 9542950
TI  - Intravitam diagnosis of human rabies by PCR using saliva and cerebrospinal fluid.
AB  - An optimized reverse transcription (RT)-PCR protocol for the intravitam detection
      of rabies virus genomic RNA was tested with clinical samples obtained from 28
      patients suspected of having rabies, 9 of whom were confirmed to have had rabies
      by postmortem examination. RT-PCR using saliva combined with an
      immunofluorescence assay performed with skin biopsy samples allowed detection of
      rabies in the nine patients.

PMID- 9542952
TI  - Development of a monoclonal antibody to a Ureaplasma urealyticum serotype 9
      antigen.
AB  - We produced a monoclonal antibody (MAb) to Ureaplasma urealyticum Vancouver, the
      serotype 9 standard strain. By immunoblotting, this MAb showed a single, 85-kDa
      band with the homologous serotype and a minor, 100-kDa band with serotype 2 but
      did not react with any other serotype standard strain. Clinical isolates of U.
      urealyticum were tested with this MAb and with two sets of polyclonal antisera
      against the 14 serotype standard strains. The use of MAb 9-2H9 correctly
      identified certain serotype 9 strains but did not react with wild-type strains
      lacking the serotype 9 determinant.

PMID- 9542953
TI  - Application of an optimized and highly discriminatory method based on arbitrarily
      primed PCR for epidemiologic analysis of methicillin-resistant Staphylococcus
      aureus nosocomial infections.
AB  - The optimization of an arbitrarily primed PCR method for typing 96 methicillin
      resistant Staphylococcus aureus (MRSA) isolates was compared with pulsed-field
      gel electrophoresis. Identical results in the differentiation of MRSA clones and
      identification of the main cluster that included 82 strains (88% of patients)
      were obtained by both techniques.

PMID- 9542954
TI  - Bile-esculin test for presumptive identification of enterococci and streptococci:
      effects of bile concentration, inoculation technique, and incubation time.
AB  - The bile-esculin test is used to differentiate enterococci and group D
      streptococci from non-group D viridans group streptococci. The effects on test
      performance of the concentration of bile salts, inoculum, and duration of
      incubation were examined with 110 strains of enterococci, 30 strains of
      Streptococcus bovis, and 110 strains of non-group D viridans group streptococci.
      Optimal sensitivity (> 99%) and specificity (97%) of the bile-esculin test can be
      obtained with a bile concentration of 40%, a standardized inoculum of 10(6) CFU,
      and incubation for 24 h.

PMID- 9542955
TI  - Detection of JC virus in cerebrospinal fluid (CSF) samples from patients with
      progressive multifocal leukoencephalopathy but not in CSF samples from patients
      with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis.
AB  - JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF) samples from
      patients with progressive multifocal leukoencephalopathy (PML) but not in CSF
      samples from patients with herpes simplex encephalitis, enteroviral meningitis,
      or multiple sclerosis. This suggests that inflammatory processes in the brain do
      not necessarily reactivate JCV, which further supports the proposal that the
      presence of JCV DNA in the CSF is diagnostic for PML.

PMID- 9542956
TI  - Long-term survival of Streptococcus pneumoniae at room temperature on Dorset egg
      medium.
AB  - Forty-five isolates of Streptococcus pneumoniae were inoculated on Dorset egg and
      supplemented Columbia agar base media, incubated overnight at 37 degrees C, and
      then kept at room temperature (RT; 21 degrees C) or 4 degrees C. Long-term
      viability was best at RT for both media, with all isolates remaining viable on
      Dorset egg medium for 44 days; viability was 90 and 57% on Columbia agar base
      medium after 7 and 30 days. We recommend the use of Dorset egg medium for the
      maintenance of pneumococci at RT.

PMID- 9542957
TI  - Phylogenetic relationships among highly virulent Newcastle disease virus isolates
      obtained from exotic birds and poultry from 1989 to 1996.
AB  - Newcastle disease virus [NDV (avian paramyxovirus type 1 [APMV1])] isolates were
      recovered from imported exotic birds confiscated following importation into the
      United States, from waterbirds in the United States, and from poultry. The exotic
      birds probably originated from Central and South America, Asia, and Africa. The
      NDV isolates were initially characterized as highly virulent because of a short
      mean death time in embryonated chicken eggs. The isolates were typed as
      neurotropic or viscerotropic velogenic by intracloacal inoculation of adult
      chickens. Intracerebral pathogenicity index values for the virulent NDV isolates
      ranged from 1.54 to 1.90, compared to a possible maximum value of 2.0. These
      isolates had a dibasic amino acid motif in the fusion protein cleavage site
      sequence required for host systemic replication. Sequence differences were
      detected surrounding the fusion protein cleavage site and the matrix protein
      nuclear localization signal, indicating evolution of highly virulent NDV.
      Phylogenetically, these isolates were categorized with other highly virulent NDV
      strains that caused outbreaks in southern California poultry during 1972 and in
      cormorants in the north central United States and southern Canada during 1990 and
      1992. These isolates are related to NDV that may have the APMV1 strain
      chicken/Australia/AV/32 or a related virus as a possible progenitor. Recent
      virulent NDV isolates and those recovered during disease outbreaks since the
      1970s are phylogenetically distinct from current vaccine viruses and standard
      challenge strains.

PMID- 9542958
TI  - Disseminated invasive infection due to Metarrhizium anisopliae in an
      immunocompromised child.
AB  - The first reported human case of possible disseminated infection with the insect
      pathogen Metarrhizium anisopliae var. anisopliae, a fungus which has been used
      commercially for biocontrol of insects, is described. The patient, a 9-year-old
      boy, had a 5-year history of pre-B-cell acute lymphoblastic leukemia and had been
      on chemotherapy throughout this period. After 10 days of profound neutropenia,
      lesions consistent with ecthyma gangrenosum appeared on his arms and legs. M.
      anisopliae was grown from specimens from three separate sites, collected at
      different times over a period of 1 month: a skin biopsy, a swab from the base of
      a lesion, and the core of another skin lesion which spontaneously discharged. The
      initial skin biopsy also showed histological evidence of epidermal necrosis and
      dermal invasion with fungal hyphae. A computed-tomography (CT) scan of the chest
      demonstrated a lesion in the superior segment of the lower lobe of the left lung.
      A CT scan of the brain revealed a lesion in the left temporoparietal region of
      the brain, consistent with an abscess. Despite antifungal treatment including
      liposomal amphotericin and 5-flucytosine, the patient eventually died. The
      initial portal of entry is unknown, but hematogenous dissemination to the skin
      appears likely because of the multiple ecthymic lesions, and the appearances of
      the brain lesion on the CT scan are consistent with a hematogenous fungal
      abscess.

PMID- 9542959
TI  - Diagnosis of Mycoplasma pneumoniae infection in autopsy and open-lung biopsy
      tissues by nested PCR.
AB  - A nested PCR specific for the Mycoplasma pneumoniae P1 gene was used to diagnose
      mycoplasma infection in two cohort patients with severe pneumonia within 24 h of
      tissue receipt. A postmortem diagnosis of M. pneumoniae infection was obtained
      for the first patient, who died without the collection of appropriate paired
      samples for serodiagnosis. An open-lung biopsy obtained from the second patient
      allowed a quick, definitive diagnosis and proper selection of therapy.

PMID- 9542960
TI  - Corneal ulcer caused by Nocardia asteroides in a patient with leprosy.
AB  - Nocardia asteroides is a rare cause of keratitis usually associated with trauma.
      We report a case of corneal ulceration caused by N. asteroides in a patient with
      leprosy. This is the first case report of nocardial keratitis from Southeast
      Asia. The diminished corneal sensation in a patient with leprosy could be a
      predisposing factor for development or exacerbation of corneal ulceration.

PMID- 9542961
TI  - Chromogenic tube test for presumptive identification or confirmation of isolates
      as Candida albicans.
AB  - This report describes a new, modified, simple, and cost-effective method for the
      use of CHROMagar Candida (CHROMagar Company, Paris, France) for the presumptive
      identification of isolates as Candida albicans after preliminary growth. Sixty
      randomly selected clinical isolates were evaluated, including 38 of C. albicans.
      With incubation at 37 degrees C for 24 h, the sensitivity and specificity
      appeared to be excellent and the test performed better than the traditional germ
      tube test. However, at earlier times, C. tropicalis isolates gave false-positive
      results.

PMID- 9542962
TI  - Nosocomial pneumonia caused by three genetically different strains of Legionella
      pneumophila and detection of these strains in the hospital water supply.
AB  - A 44-year-old woman developed Legionella pneumophila pneumonia after cerebral
      surgery. Initially, one colony from a clinical specimen and two colonies from
      water samples, all belonging to serogroup 12, did not match when their DNA
      restriction patterns were compared. When additional colonies from the water
      specimens were analyzed, a serogroup 12 strain complementary to that found in the
      clinical specimen was identified. Other colonies from the clinical specimen were
      identified as serogroup 12 strains complementary to those identified from the
      water. In addition, the same serogroup 1 strain was isolated from the patient and
      the water system.

PMID- 9542963
TI  - Effect of nonionic detergents on amplification of human papillomavirus DNA with
      consensus primers MY09 and MY11.

PMID- 9542964
TI  - Discrepancies between E-test and agar dilution methods for testing metronidazole
      susceptibility of Helicobacter pylori.

PMID- 9542966
TI  - CFTR gene and male fertility.
AB  - Secretion of electrolytes and water by the epididymal epithelium is important in
      the formation an optimal fluid environment for sperm maturation and transport.
      This process is disrupted in the genetic disease cystic fibrosis caused by
      mutation of the cystic fibrosis transmemebrane conductance regulator (CFTR) gene.
      Recent findings of CFTR gene mutations in healthy men with congenital bilateral
      absence of the vas deferens or poor sperm quality may indicate that CFTR gene
      mutations have a far-reaching effect on human reproduction.

PMID- 9542965
TI  - Clostridium difficile bacteremia in an immunocompetent child.

PMID- 9542967
TI  - The fatty acid composition of phospholipids of spermatozoa from infertile
      patients.
AB  - The lipid composition of the sperm membrane has a significant effect upon the
      functional characteristics of spermatozoa. In the present study we investigated
      the fatty acid (FA) composition of subpopulations of spermatozoa separated on a
      discontinuous Percoll gradient (47:90%) and the FA composition of phospholipids
      (PL) of sperm heads and tails in both normal and abnormal semen samples. In
      normozoospermic samples, polyunsaturated fatty acids (PUFA) represented 34.0 +/-
      1.3 (mean +/- SE, mole %) and 25.6 +/- 1.2% of total FA of PL of the 47 and 90%
      Percoll fractions respectively. Docosahexaenoic acid (22:6omega3, DHA)
      contributed to more than 60% of total PUFA. DHA was significantly lower in both
      the 47% (P < 0.05) and the 90% (P < 0.01) Percoll fractions of oligozoospermic
      samples and in the 90% Percoll layer of asthenozoospermic samples (P < 0.01),
      compared with normozoospermic samples. The omega6/omega3 ratio was significantly
      increased in both Percoll fractions of samples with oligozoospermia (47%, P <
      0.001 and 90%, P < 0.001) or with asthenozoospermia (47%, P < 0.05 and 90%, P <
      0.001) compared with normozoospermic samples. The oxidative potential index (OPI)
      of spermatozoa recovered from the 47% Percoll layer was significantly higher (P <
      0.0001) than of those recovered from the 90% Percoll. Mean melting point (MMP),
      an index of membrane fluidity, was significantly lower in head than in tails (P <
      0.01) of spermatozoa, and also in both the 47% (P < 0.01) and 90% (P < 0.001)
      Percoll fractions of normozoospermic samples in comparison with oligozoospermic
      samples. The MMP was significantly higher (P < 0.05) in samples of patients with
      idiopathic oligo/asthenozoospermia, varicocele, and male accessory gland
      infection (MAGI). These differences in FA composition of PL in subpopulations of
      human spermatozoa, and in their heads and tails may be related to sperm maturity
      and to differences in physiological function.

PMID- 9542968
TI  - Specific localization in the equatorial region of gp20, a 20 kDa
      sialylglycoprotein of the capacitated human spermatozoon acquired during
      epididymal transit which is necessary to penetrate zona-free hamster eggs.
AB  - In this study we set out to characterize gp20, a 20 kDa glycoprotein of the human
      sperm surface, first identified by us by radiolabelling the sialic acid residues
      of the sperm surface [R. Focarelli et al. (1995), Mol. Hum. Reprod., 2, 2755
      2759]. The protein was partially purified from pooled sperm samples of several
      healthy donors and used to raise a specific antiserum to study its localization
      in the reproductive system. When tested with freshly ejaculated spermatozoa, the
      anti-gp20 antibody intensely stained the head and midpiece. However, on
      capacitated spermatozoa the antigen was restricted to a sharp zone in the
      equatorial region. The antibody did not bind to differentiating germ cells but
      the antigen was present in epididymal epithelial cells and also in seminal
      plasma. Anti-gp20 exerted a blocking effect in a test for sperm penetration of
      zona-free hamster eggs, thus suggesting that gp20 is involved in the early stages
      of fertilization.

PMID- 9542969
TI  - In-situ competition between protamine and fluorochromes for sperm DNA.
AB  - In this study we investigated the relationship between the presence of bound
      protamine on mouse and human sperm DNA and the level of chromomycin A3 (CMA3) and
      4'6-diamidino-2-phenylindole (DAPI) fluorescence. This was accomplished by
      performing a competition assay between salmon protamine and fluorochromes on
      decondensed spermatozoa that had their nuclear proteins extracted and were fixed
      on slides. Various concentrations (0, 0.005, 0.0225, 0.05, 0.225, 0.5 and 5
      mg/ml) of salmon protamine were added to either the CMA3 or DAPI staining
      solutions. Fluorescence emission measurements of stained sperm nuclei were then
      performed using a microfluorometer. When the treated decondensed sperm heads were
      stained with either CMA3 or DAPI all spermatozoa were found to fluoresce
      intensely. The addition of protamines to the spermatozoa led to an elimination of
      CMA3 fluorescence, while the intensity of DAPI staining was decreased to
      approximately 50% at the highest concentrations of protamine. The addition of
      increasing amounts of salmon protamine also induced the sperm nuclei to regain
      their initial condensed appearance. This study shows that protamine retains a
      strong affinity for sperm DNA in situ and that CMA3 fluorescence is a strong
      indicator of the protamination state of spermatozoa.

PMID- 9542970
TI  - In-vitro human spermatozoa nuclear decondensation assessed by flow cytometry.
AB  - The process of sperm chromatin decondensation occurs when a spermatozoon enters
      an ovum. Protamine disulphide bonds are reduced to SH and the polycationic
      protamines combine with the polyanionic egg protein, nucleoplasmin, thus being
      stripped from DNA which then combines with histones. Defective chromatin
      decondensation will thus prevent further development of the male pronucleus. In
      this study human sperm samples were incubated in vitro at 28 degrees C (using a
      medium in which the polyanion, heparin, substitutes for nucleoplasmin and beta
      mercaptoethanol for egg glutathione) for 10, 20 and 30 min before stopping the
      reaction with formalin (to 3.6%). The DNA of the fixed cells was stained with
      Acridine Orange by a one-step method and subjected to flow cytometry and data
      analysis, in which a zone characteristic of condensed chromatin is outlined on
      red-green fluorescence contour plots. After 20 min of incubation 97% of the
      control spermatozoa that were in the mature window (WIN M) had decondensed and
      moved out of this region. Defects in sperm decondensation were seen in four semen
      samples of the 20 that were tested. In cases where spermatozoa fail to produce a
      fertilized egg the cause may lie with defective chromatin quality, including
      failure of the sperm chromatin to decondense. The method described here is a
      simple procedure for detecting sperm samples containing such defective cells.

PMID- 9542971
TI  - Effect of maternal age and conditions of fertilization on programmed cell death
      during murine preimplantation embryo development.
AB  - One of the major morphological anomalies observed in many human pre-embryos is
      extensive cellular fragmentation. Previously we confirmed that embryo
      fragmentation seemed to be associated with the activation of programmed cell
      death (PCD). The purpose of our experiments was to establish a rate for murine
      embryo fragmentation in vivo after hormonal stimulation in young versus older
      females and to compare it with the rate of embryo fragmentation during in-vitro
      fertilization (IVF). While murine maternal age beyond 40 weeks increased the rate
      of embryo fragmentation following in-vivo fertilization (P = 0.001), oocytes from
      females of all ages had a uniformly high rate of fragmentation when fertilized in
      vitro (33%). None of the fragmented murine embryos proceeded further in
      development. In the mouse, fragmentation occurs exclusively during the first cell
      cycle. Furthermore, IVF significantly reduced the rate of blastocyst formation (P
      = 0.0001) and decreased the mean cell number at the blastocyst stage in
      comparison with embryos produced in vivo (P < 0.0001). The cell death index was
      significantly affected by both maternal age (P = 0.005) and IVF (P = 0.0001).
      Identification of specific factors which trigger PCD, especially those associated
      with IVF, may enable us to lower the rates of fragmentation in preimplantation
      embryos and thereby increase pregnancy rates after human IVF.

PMID- 9542972
TI  - A rapid method for the measurement of the oxoreductase activity of 11beta
      hydroxysteroid dehydrogenase in granulosa-lutein cells from patients undergoing
      in-vitro fertilization.
AB  - The presence of 11beta-hydroxysteroid dehydrogenase (11beta-HSD; EC1.1.1.146),
      the enzyme responsible for the interconversion of cortisol and cortisone, in
      granulosa-lutein (GL) cells is associated with a poor outcome in in-vitro
      fertilization (IVF). We have developed a simple method of assessing the reductase
      component of 11beta-HSD in these cells which is sufficiently rapid to provide
      data on the enzyme's activity prior to embryo replacement. Cells were pooled from
      follicular aspirates and challenged with cortisone within 2 h of aspiration.
      Cortisol secretion was then measured by radioimmunoassay. Conversion of cortisone
      to cortisol was linear for up to 3 h and was completely inhibited by
      glycyrrhetinic acid, a specific 11beta-HSD inhibitor. Initial velocity rates were
      determined for eight cortisone concentrations (range 0.1-8 micromol/l), and the
      apparent Km calculated (1.6 +/- 0.4 micromol/l). There was no evidence of
      substrate/product inhibition and conversion of cortisone to cortisol was <2% in
      all experiments. In subsequent work, cells were challenged with cortisone (6
      micromol/l) for 2 h. Cells challenged for 2 h immediately following purification
      from follicular aspirates produced varying amounts of cortisol (range 25-150
      nmol/pooled follicles from each patient, n = 10 patients), while basal outputs
      were <6 nmol/l. Enzyme activity was also examined in cells on a per follicle
      basis from individual patients and found to vary considerably (e.g. 19, 53 and 36
      nmol/l cortisol/1000 cells, three follicles). Having established the method for
      assessing 11beta-reductase activity within GL cells, we performed a small
      prospective study on a series of 20 patients examining the enzyme activity within
      110 individual follicles. 11Beta-reductase activity varied greatly from patient
      to patient and from follicle to follicle ranging from <0.024-0.57 nmol
      cortisol/microg DNA but at present low patient numbers preclude a meaningful
      correlation between enzyme activity and pregnancy rate. In summary, we have
      developed a simple, rapid (<8 h) assay for detecting the reductase activity of
      11beta-HSD in GL cells isolated from pooled or individual follicles. This
      procedure is sufficiently quick to aid in the choice of embryo for replacement.

PMID- 9542973
TI  - Expression of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA in
      embryos and endometrial stromal cells.
AB  - The objective of the present study was to investigate the effects of insulin-like
      growth factor-binding protein-1 (IGFBP-1) on the interaction between mouse
      embryos and endometrial stromal cells in co-culture systems. To explore
      quantitatively the changes in expression of IGFBP-1 mRNA from endometrial stromal
      cells cultured alone or co-cultured with embryos, a combination of reverse
      transcription-polymerase chain reaction (RT-PCR) and Southern blotting followed
      by a densitometric analysis was used. In co-culture systems, development of
      embryos was significantly improved and the production of IGFBP-1 from endometrial
      stromal cells was stimulated by the embryos. Quantitative analysis showed that
      expression of IGFBP-1 mRNA in endometrial stromal cells co-cultured with embryos
      was higher on days 3,5 and 8 (1.6-, 4.5- and 2.3-fold respectively) than in
      endometrial stromal cells cultured alone. In addition, intensity of PCR products
      for IGFBP-1 mRNA in endometrial stromal cells co-cultured with embryos was higher
      on day 5 than on days 3 and 8. However, the expression of IGFBP-1 mRNA in embryos
      cultured alone was very low. In conclusion, co-culture of embryos with
      endometrial stromal cells improved the development of embryos and may be
      associated with the production of IGFBP-1 by the co-cultured endometrial stromal
      cells. A combination of RT-PCR and Southern blotting followed by a densitometric
      analysis appeared to be a sufficiently quantitative method to determine changes
      in IGFBP-1 mRNA values.

PMID- 9542974
TI  - Immunodetection of benzo[a]pyrene adducts in ovarian cells of women exposed to
      cigarette smoke.
AB  - Benzo[a]-pyrene (B[a]P) is a potent mutagen and carcinogen present in cigarettes.
      We report here on immunodetection and quantification of B[a]P-DNA adducts in
      granulosa-lutein cells of patients undergoing in-vitro fertilization (IVF) and
      embryo transfer, who were exposed to cigarette smoke. Follicular fluids (FF) and
      granulosa-lutein cells were obtained from the same follicular aspirate from 32
      women self-reported as active smokers, passive smokers, or non-smokers. Cells
      were immunostained with 5D11, an anti-B[a]P diolepoxide monoclonal antibody that
      recognizes DNA adducts. Cotinine, a reliable marker for recent smoke exposure and
      dose, was assessed by radioimmunoassay in 32 FF samples. Individual scores of
      cell immunoreactivity were highly correlated with FF cotinine concentrations.
      Evaluations of immunostaining intensity in 9770 granulosa-lutein cells from the
      32 women revealed higher average scores in active and passive smokers, relative
      to non-smokers. In passive smokers the average level of cell immunostaining was
      63% of that of active smokers. These relationships provide quantitative evidence
      that B[a]P-DNA adduct levels are related to smoke exposure and dose, both recent
      and long term. Immunostaining was confined to the nucleus, suggesting adduct
      formation by covalent binding to DNA. Presence of adducts in granulosa-lutein
      cells from women exposed to cigarette smoke may increase the risk for DNA damage.

PMID- 9542975
TI  - Preimplantation genetic diagnosis of chromosome balance in embryos from a patient
      with a balanced reciprocal translocation.
AB  - Duplications or deletions are present in a high percentage of the gametes
      produced by individuals carrying balanced translocations. Preimplantation genetic
      diagnosis was used to examine chromosome balance in embryos from a patient having
      a reciprocal translocation within the short arms of chromosomes 5 and 8
      (46,XX,t(5;8)(p13;p23)). This woman has two sisters with the translocation
      unbalanced, resulting in a partial trisomy for chromosome 5 and partial monosomy
      for chromosome 8 (46,XX,-8, +der(8)t(5;8)(p13;p23)) with associated mental
      retardation and physical abnormalities. The patient and her husband desired to
      have children without the abnormal chromosome balance and wished to reduce the
      likelihood of spontaneous abortion or need for therapeutic abortion. Fluorescence
      in-situ hybridization (FISH) probes for the alpha-satellite region of chromosome
      8 and for a region on the short arm of chromosome 5 (5p15.2) were tested
      initially on lymphocytes from the patient and her sisters. The hybridization
      signal for chromosome 5 was detected in the expected two copies for the patient
      and three copies for the sisters in 87% of the cells. Two hybridization signals
      for chromosome 8 were detected in 96% of the cells from all individuals.
      Additional probe testing was done using blastomeres from polyspermic embryos. The
      couple then proceeded with a stimulated in-vitro fertilization (IVF) cycle and
      biopsies were done on 13 embryos at the 7-10-cell stage using a method of zona
      drilling and fluid displacement. Diagnosis was possible on at least one
      blastomere for nine embryos. Three embryos had nuclei with three hybridization
      signals for chromosome 5, three had fewer than two signals for one or both
      chromosomes, one was mosaic, and two had two signals for each chromosome. The
      latter were transferred to the patient, but pregnancy was not achieved. The
      results demonstrate that preimplantation genetic diagnosis for patients with
      reciprocal translocations can be used to identify embryos having normal
      chromosome balance. The potential advantages and limitations of this approach are
      discussed.

PMID- 9542976
TI  - Telomerase activity in the human endometrium throughout the menstrual cycle.
AB  - In a total of 41 endometrial tissue samples, the relationship between telomerase
      activity and proliferating cell nuclear antigen (PCNA) labelling index was
      studied. In samples of endometrium from the proliferative phase of the menstrual
      cycle, telomerase activity was found in 15 out of 17 cases (88%). Two samples
      from the early proliferative phase showed negative telomerase activity and a low
      PCNA labelling index. However, three out of 16 samples of early secretory phase
      endometrium showed telomerase activity and a PCNA labelling index. In mid- to
      late secretory phase endometrium, in menopausal endometrium and in decidualized
      endometrium induced by progesterone neither telomerase activity nor PCNA
      labelling was found. These results suggest that telomerase activity of the
      endometrium may be correlated with the proliferative potential of the epithelial
      cells and that its activity may be regulated by oestrogen.

PMID- 9542977
TI  - The presence of chorionic gonadotrophin beta subunit in normal cyclic human
      endometrium.
AB  - The aim of the present study was to determine whether human endometrial cells are
      able to secrete beta-chorionic gonadotrophin (betaCG). Immunohistochemical
      studies and in-situ hybridization were performed in order to provide evidence for
      the occurrence of betaCG in the normal endometrium in 15 patients in the
      proliferative phase, two patients in the periovulatory phase and 13 patients in
      the secretory phase. Neither immunohistochemical nor hybridization reactions
      could be recognized during the proliferative phase. In contrast, both protein and
      betaCG mRNA were observed in the glandular cells of the endometrium during the
      secretory phase. The results were supported by Western blotting of secretory
      phase endometrium extracts and the assessment of the functional secretory
      capacity of primary endometrium cultures. In comparison with cultured and
      separated cell fractions, tissue extracts showed a higher betaCG, indicating a
      regulatory interaction. In conclusion, betaCG can be demonstrated in normal human
      cyclic endometrium, suggesting a paracrine role in endometrial physiology.

PMID- 9542978
TI  - Endothelin receptor expression in human decidua.
AB  - The endothelins are signalling peptides that act via two receptors, ET(A) and
      ET(B). In the human endometrium, endothelin receptors have been demonstrated in
      glands and stroma and have been shown to vary during the course of the menstrual
      cycle. The present study was undertaken to determine whether or not expression of
      endothelin receptors changes during pregnancy or after administration of
      exogenous progestagens. The expression of the receptors was correlated with the
      appearance of basement membrane components during decidualization of the
      endometrial stroma. Decidual specimens (n = 15) were obtained during the first
      trimester of pregnancy and 10 at term. Sixteen pairs of endometrial biopsies were
      obtained from women with menorrhagia before and after exposure to exogenous
      progestagens. A total of 15 hysterectomy specimens were used as controls for the
      expression of stromal basement membrane proteins in the absence of
      decidualization. Autoradiography was carried out with selective ligands for ET(A)
      ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of ligand binding
      was then compared with the distribution of laminin alpha2 light chain and
      collagen IV. ET(A), ET(B), laminin alpha2 light chain, and collagen IV were
      expressed in stromal decidual cells in the first trimester of pregnancy. ET(B)
      was also found on endometrial glandular epithelium. Quantitative macro
      autoradiography and multiple regression analysis demonstrated a highly
      significant positive correlation (P < 0.001) between expression of ET(B) and
      laminin alpha2 light chain. In the third trimester qualitative examination
      suggested a reduction of ET(A) in the stroma. Progestagen-induced decidua
      exhibited a similar pattern to that found in first trimester decidua. This study
      has demonstrated up-regulation of ET(B) during the progesterone-dependent process
      of decidualization and suggests a paracrine or autocrine role for endothelins in
      the decidua.

PMID- 9542979
TI  - Expression of the Kir2.1 (inwardly rectifying potassium channel) gene in the
      human placenta and in cultured cytotrophoblast cells at different stages of
      differentiation.
AB  - The aim of this study was to investigate whether the Kir2.1 gene is expressed by
      the human placenta throughout pregnancy and in cytotrophoblast cells at different
      stages of differentiation in culture. RNA was extracted from cytotrophoblast
      cells isolated from term placentas and maintained in culture for 18, 66 and 114 h
      and from first, second and third trimester placentas. Using the reverse
      transcriptase-polymerase chain reaction (RT-PCR) with gene-specific primers, a
      cDNA product of 1.2 kb, as expected for Kir2.1 gene expression, was detected in
      all the RNA samples from cytotrophoblast cells and from placentas. The RT-PCR
      products were verified by sequencing and by detection of the expected transcript
      size for the Kir2.1 mRNA at 5.6-5.7 kb on Northern blots, using the 1.2 kb cDNA
      generated by RT-PCR. Northern blot quantification, using a control 28S rRNA
      probe, showed no significant difference in Kir2.1 mRNA expression between any of
      the three stages of cytotrophoblast cell differentiation studied (ANOVA; n = 3
      RNA samples from each stage). These data demonstrate that the Kir2.1 gene is
      expressed by the human placenta and, specifically, by cytotrophoblast cells, at
      all stages of development and differentiation.

PMID- 9542981
TI  - Salvage treatment of failed hallux valgus operations with proximal first
      metatarsal osteotomy and distal soft-tissue reconstruction.
AB  - We reviewed the results of 15 patients (16 feet) in whom a hallux valgus
      procedure had failed. Salvage was by proximal crescentic first metatarsal
      osteotomy with distal soft-tissue reconstruction. Results based on a clinical
      scale considering the level of pain, activity limitations, support requirement,
      footwear limitations, and alignment were good in 11, fair in two, and poor in
      three. Patients were satisfied with the results in 10 feet, satisfied with
      reservations in four feet, and dissatisfied in two feet. Complications were:
      transfer metatarsalgia in three, hallux varus in one, and osteotomy nonunion in
      one. One of the patients required reoperation to bone graft a proximal osteotomy.
      Metatarsal osteotomy was helpful in the salvage treatment of recurrent,
      symptomatic hallux valgus when the first metatarsophalangeal joint was functional
      and painless.

PMID- 9542982
TI  - Effect of medial displacement calcaneal osteotomy on ankle kinematics in a
      cadaver model.
AB  - Although medial displacement calcaneal osteotomy has been advocated for treatment
      of acquired pes planus, no studies have determined the biomechanical consequences
      at the ankle of such a procedure. The present investigation examined the
      alteration in ankle motion that resulted from a medial sliding calcaneal
      osteotomy. In dorsiflexion, the ankle specimens were found to have altered
      internal rotation and varus alignment. At maximal dorsiflexion, there was a 76%
      increase in internal rotation (4.4 degrees +/- 2.5 degrees versus 2.5 degrees +/-
      1.7 degrees for intact ankles, P < 0.0004) and an increase of 425% in varus (0.42
      degrees +/- 0.56 degrees versus 0.08 degrees +/- 0.34 degrees for intact ankles,
      P < 0.003). There were no significant differences seen in plantar flexion. Based
      on these results, caution is advised in the indiscriminate use of medial sliding
      osteotomies, because this procedure may predispose the patient to premature ankle
      arthritis as a consequence of the altered ankle motions.

PMID- 9542983
TI  - Surgical treatment of patients with painful instability of the second
      metatarsophalangeal joint.
AB  - An unstable second metatarsophalangeal joint may produce pain in the forefoot.
      Eighteen patients (20 feet) had a transfer of the flexor digitorum longus to the
      extensor side of the base of the proximal phalanx performed as the primary
      procedure to stabilize this painful joint. Most patients had a hallux valgus
      deformity that also required correction, because it either was also symptomatic
      or was preventing adequate reduction of the second toe. A ruptured plantar plate
      of the second metatarsophalangeal joint was demonstrated in 13 feet and in these
      joints appeared to be the cause of the vertical instability. However, all feet
      showed an unstable joint upon clinical examination. A vertical-stress test almost
      always reproduced the patient's pain while demonstrating instability in the
      joint; this was the most prominent physical finding in these patients. Eleven
      patients (13 feet) had an excellent result. Seven patients (seven feet) had a
      fair result, but they complained only of mild and occasional pain at the joint on
      exertion. Although difficult to quantify, it appears that postoperative stiffness
      in the joint provided some of the joint stability seen in our patients. The
      flexor tendon transfer appears to be a satisfactory method to treating the
      unstable metatarsophalangeal joint and of relieving patients' pain, but may not,
      however, restore a normal alignment of the second toe. Correction of other
      forefoot deformities as hallux valgus and hammertoes may also be important in
      restoring metatarsophalangeal stability.

PMID- 9542984
TI  - An evaluation of the use of gait plate inlays in the short-term management of the
      intoeing child.
AB  - A method of short-term intervention in cases of symptomatic intoeing in young
      children was evaluated. Foot placement angle (FPA) in subjects (N = 18) suffering
      from symptomatic intoeing was compared before and during the wearing of "gait
      plate" inlays in the footgear. The median preintervention FPA in the study group
      was -9.5 degrees (i.e., 9.5 degrees of intoeing). After the addition of gait
      plate inlays, this angle fell to -3.5 degrees (Wilcoxon's matched pairs test P <
      0.0001). There was no correlation found between the site of the underlying
      pathology, gender, or age in relation to either the degree of original intoeing
      or resulting improvement. There was a significant negative correlation
      (Spearman's correlation coefficient -0.512, P < 0.001) between the FPA at
      diagnosis and the subsequent improvement.

PMID- 9542985
TI  - Biomechanical consequences of sequential plantar fascia release.
AB  - Plantar fascia release has long been a mainstay in the surgical treatment of
      persistent heel pain, although its effects on the biomechanics of the foot are
      not well understood. With the use of cadaver specimens and digitized computer
      programs, the changes in the medial and lateral columns of the foot and in the
      transverse arch were evaluated after sequential sectioning of the plantar fascia.
      Complete release of the plantar fascia caused a severe drop in the medial and
      lateral columns of the foot, compared with release of only the medial third.
      Equinus rotation of the calcaneus and a drop in the cuboid indicate that strain
      of the plantar calcaneocuboid joint capsule and ligament is a likely cause of
      lateral midfoot pain after complete plantar fascia release.

PMID- 9542986
TI  - Differences in impulse distribution in patients with plantar fasciitis.
AB  - The impulse distribution based upon vertical foot-floor reaction forces and time
      under the fore-, mid-, and hindfoot was determined using Tekscan's F-Scan system.
      This was compared in 40 barefoot patients with long-standing plantar fasciitis
      with an equal number of normal subjects. The patient group tended to load the
      hind- and midfoot to a lesser extent than the control group. Consequently, a
      greater proportionate load was borne by the forefoot. This result was highly
      significant for both the midfoot (P < 0.001) and forefoot (P = 0.002)
      comparisons. An objective biomechanical method such as this may be useful as a
      diagnostic aid, to identify individuals predisposed to this condition, and for
      evaluating the efficacy of various treatment modalities.

PMID- 9542987
TI  - Stress fracture of the base of the third metatarsal after an endoscopic plantar
      fasciotomy: a case report.

PMID- 9542988
TI  - Treatment of diabetic (neuropathic) foot ulcers with two-stage debridement and
      closure.
AB  - We reviewed 33 patients with 37 wounds treated between November of 1991 and
      December of 1995 in the Wound Care Center. A two-stage debridement and closure
      technique for neuropathic foot ulcers was performed. Patients selected included
      those with obvious osteomyelitis and those who had failed nonsurgical treatment.
      The approach included initial surgical excision of the ulcer with biopsy, bone
      resection with biopsy, and deep culture. The second-stage procedure 4 to 8 days
      later included debridement of the wound and delayed closure. Intravenous
      antibiotic treatment using a central line was given postoperatively in patients
      with documented osteomyelitis for at least 6 weeks and in patients with infected
      soft tissues only for about 4 weeks. All patients remained nonweightbearing for 4
      weeks; this was felt necessary to prevent separation of the wound edges. Four
      wounds in four patients failed to heal, and two of these went on to amputation.
      Satisfactory healing occurred in 29 of 33 patients and in 33 of 37 wounds. The
      authors conclude that two-stage surgical debridement and closure is an acceptable
      treatment in selected nonhealing diabetic (neuropathic) foot ulcers.

PMID- 9542989
TI  - Results of preprocedure and postprocedure toe cultures in orthopaedic surgery.
AB  - This study was to determine whether there is any benefit to wrapping the toes
      sterilely during orthopaedic procedures not involving the foot but performed on
      the lower extremity. The group studied consisted of 12 patients who had an
      orthopaedic procedure performed in which the foot and toes were included in the
      surgical prep, but not involved in the surgical procedure. Nine of the 12
      patients (75%) had positive results from preprocedural aerobic cultures and two
      of the 12 (16.6%) had positive results from preprocedural fungal cultures.
      Recolonization of the bacteria between the toes was also demonstrated. Sterile
      draping of the toes would minimize the risk of infection and also protect against
      bacteria that recolonize during the procedure.

PMID- 9542990
TI  - Piperacillin/tazobactam therapy for diabetic foot infection.
AB  - In this study, 29 patients were hospitalized with a diabetic foot infection and
      were treated with piperacillin/tazobactam. Of these 23 patients who were
      evaluated for efficacy of treatment, 22 patients improved or were clinically
      cured. In seven patients (30%), there was persistence of one of the baseline
      pathogens. Adverse events were reported in 15 patients (58%), three of which were
      serious. Piperacillin/tazobactam may be useful as monotherapy in diabetic foot
      infection giving an adequate clinical response and the level of side effects
      equivalent to those of other broad-spectrum antibiotics.

PMID- 9542991
TI  - Risk of contamination of the wound in a hydrotherapeutic tank.
AB  - Over a 4-week period, samples for culture were taken from active hydrotherapeutic
      tanks (whirlpools) from two institutions in a university medical center. Samples
      were obtained in the morning before treatments began, and in the evening after,
      the final patient had been treated. Specific attention was directed toward
      recovery of S. aureus, P. aeruginosa, and E. coli, organisms felt to be
      especially dangerous for the diabetic dysvascular patients utilizing the
      hydrotherapeutic tanks involved in this study. Only eleven of 96 cultures (11.5%)
      were positive for these prospective pathogens. Of the positive cultures, nine
      (9.4%) were taken from near the agitator-jet, and only two (2.1%) from the floor
      of the hydrotherapeutic tanks, where the extremity is likely to be placed. Our
      results reveal that hydrotherapeutic immersion is not likely to expose patients
      with open wounds to potential iatrogenic contamination of the wound.

PMID- 9542992
TI  - An unusual cause of posterior tibial tendon degeneration.
AB  - A case demonstrating a mechanical cause of posterior tibial tendon degeneration
      is reported. The possible etiologies for degeneration of the posterior tibial
      tendon are discussed.

PMID- 9542993
TI  - Posttraumatic posterior tibialis tendon insertional elongation with functional
      incompetency: a case report.
AB  - We present a case report and literature review of distal intrasubstance rupture
      of the posterior tibial tendon with progressive pes planovalgus secondary to
      tendon incompetence. Three months after a severe ankle sprain, a 25-year-old
      basketball player presented with ankle weakness and pain. Treatment by
      advancement of the posterior tibial tendon to the navicular and medial
      displacement osteotomy of the calcaneal tuberosity restored alignment, strength,
      and full function.

PMID- 9542994
TI  - Arthroscopy of the foot and ankle: current concepts review.

PMID- 9542995
TI  - Fold recognition and molecular modeling of a lectin-like domain in UDP
      GalNac:polypeptide N-acetylgalactosaminyltransferases.
AB  - By use of threading methods, the C-terminal region of uridine diphospho-N-acetyl
      D-galactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc
      transferases) was predicted to have the same fold as the lectin-domain of the
      plant cytotoxins ricin and abrin-a, for which crystal structure are available.
      The sequence identities are very low. Nevertheless, the amino acids involved in
      the hydrophobic core essential for the structure stability and the cysteine
      residues are conserved. In addition, the amino-acids involved in carbohydrate
      binding are conserved in ppGalNAc-transferases. The extra C-terminal domain of
      these enzymes is therefore a putative glycan-binding domain. A model of the
      lectin-like domain of human ppGalNAc-transferase T1 was built using knowledge
      based methods. Geometry optimization of the complex with galactose allowed
      prediction that this domain could bind this monosaccharide. However, the
      interaction seems to be rather weak, and at the moment there is no evidence that
      ppGalNAc-transferases displays a lectin activity in vivo.

PMID- 9542996
TI  - The dimerization of Pseudomonas putida cytochrome P450cam: practical consequences
      and engineering of a monomeric enzyme.
AB  - Cytochrome P450cam dimerizes via the formation of an intermolecular disulfide
      bond, complicating the storage and handling of the enzyme, particularly at higher
      concentrations. The dimeric enzyme is 14% less active than the monomer and forms
      at a slow but significant rate even at 4 degrees C [k = 1.09 x 10(-3) mM(-1) h(
      1)]. To eliminate any ambiguity introduced by dimer formation and to simplify
      handling and storage of the enzyme, site-directed mutagenesis was used to
      identify C334 as the single cysteine residue responsible for the formation of the
      disulfide linkage and to engineer a monomeric enzyme by substituting an alanine
      in its place. The C334A mutant is identical with the wild-type P450cam monomer in
      terms of optical spectra, camphor binding and turnover activity, but shows no
      evidence of dimerization and aggregation even at millimolar concentrations.
      Preliminary 1H NMR investigations also indicate a significant improvement in the
      quality of spectra obtained with this mutant. (C334A)P450cam is therefore
      proposed as an alternative to the wild-type enzyme-a base mutant otherwise
      identical with the wild-type but with improved handling characteristics.

PMID- 9542997
TI  - A fast estimate of electrostatic group contributions to the free energy of
      protein-inhibitor binding.
AB  - Dissecting ligand-protein binding free energies in individual contributions of
      protein residues (which are referred to here as 'group contributions') is of
      significant importance. For example, such contributions could help in estimating
      the corresponding mutational effects and in studies of drug resistance problems.
      However, the meaning of group contributions is not always uniquely defined and
      the approximations for rapid estimates of such contributions are not well
      developed. In this paper, the nature of group contributions to binding free
      energy is examined, focusing particularly on electrostatic contributions which
      are expected to be well behaved. This analysis examines different definitions of
      group contributions; the 'relaxed' group contributions that represent the change
      in binding energy upon mutation of the given residue to glycine, and the 'non
      relaxed' group contributions that represent the scaled Coulomb interaction
      between the given residue and the ligand. Both contributions are defined and
      evaluated by the linear response approximation (LRA) of the PDLD/ S method. The
      present analysis considers the binding of pepstatin to endothiapepsin and 23 of
      its mutants as a test case for a neutral ligand. The 'non-relaxed' group
      contributions of 15 endothiapepsin residues show significant peaks in the
      'electrostatic fingerprint'. The residues that contribute to the electrostatic
      fingerprint are located in the binding site of endothiapepsin. They include the
      aspartic dyad (Asp32, Asp215) with adjacent residues and the flap region. Twelve
      of these 15 residues have a heavy atom distance of <3.75 A to pepstatin. The
      contributions of 8 (10) of these 12 residues can be reconciled with the
      calculated 'relaxed' group contributions where one allows the protein and solvent
      (solvent only) to relax upon mutation of the given residue to glycine. On the
      other hand, it was found that residues at the second 'solvation shell' can have
      relaxed contributions that are not captured by the non-relaxed approach. Hence,
      whereas residues with significant non-relaxed electrostatic contributions are
      likely to contribute to binding, residues with small non-relaxed contributions
      may still affect the binding energy. At any rate, it is established here that
      even in the case of uncharged inhibitors it is possible to use the non-relaxed
      electrostatic fingerprint to detect 'hot' residues that are responsible for
      binding. This is significant since some versions of the non-relaxed approximation
      are faster by several orders of magnitude than more rigorous approaches. The
      general applicability of this approach is outlined, emphasizing its potential in
      studies of drug resistance where it is crucial to have a rapid way of
      anticipating the effect of mutation on both drug binding and catalysis.

PMID- 9542998
TI  - Is there a Mobius band in closed protein beta-sheets?
AB  - Protein beta-strands can form beta-barrels and other complicated structures. This
      paper defines bifurcations and pseudobifurcations of beta-sheets. They are
      important structural elements for protein folding. This paper also presents a
      characteristic number that can be used to test whether the surface of a closed
      beta-sheet is one- or two-sided. Searching the whole Protein Data Bank released
      in April 1997 with the definition of beta-structures given by the DSSP program,
      we do not find any one-sided beta-Mobius band. However, there are interesting
      structures such as beta-bands with odd number of antiparallel ladders and odd
      number of bifurcations. There are also beta-structures that are closed only at a
      singular point. Adding a small patch near the singular point in different ways
      can make it a one- or two-sided surface. The catalytic triad of a GMP synthetase
      (1GPM) is near the singular point of such a beta-sheet.

PMID- 9543000
TI  - Structural studies of EcoRII methylase: exploring similarities among methylases.
AB  - EcoRII methyltransferase (M.EcoRII) is a cytosine-C5 DNA methylating enzyme. A
      model of its three-dimensional structure is proposed on the basis of homology
      modeling. Crystal structures of two members of the same family of enzymes, HaeIII
      and HhaI methyltransferases (M.HaeIII and M.HhaI respectively), were used as
      template molecules. Molecular dynamics was used to ensure sampling of
      conformationally stable structures. The final model has good geometry. The DNA
      and cofactor binding residues are in expected positions and form proper
      interactions. M.EcoRII is 147 amino acids longer than the template molecules, and
      hence the model contains several loops that are significantly longer than those
      in M.HaeIII and M.HhaI. The model provides a framework for interpretation and
      designing site-directed mutants that have a potential to improve crystallization
      experiments of this enzyme, and possibly other similar enzymes.

PMID- 9542999
TI  - Molecular modeling of HIV-1 reverse transcriptase drug-resistant mutant strains:
      implications for the mechanism of polymerase action.
AB  - A computer model of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) either alone, or complexed with a non-nucleoside inhibitor
      (NNI), was constructed using crystal coordinate data from a subset of the protein
      surrounding the binding pocket region. Molecular mechanics calculations were
      carried out on solvated wild-type RT and RT that contained modifications
      corresponding to resistance-engendering mutations. Results from the calculations
      revealed that the r.m.s. difference between 12 modified proteins and that of wild
      type RT could be qualitatively correlated with the measured polymerase activity
      of the enzyme in the presence of these mutations. In addition, the level of
      activity was related to the measured distance between the primer grip and dNTP
      binding regions of the protein. These data suggest a direct correlation between
      RT structure and function. Complexes of RT-8-C1 TIBO and RT-alpha-APA were also
      minimized in models containing modifications corresponding to key drug-resistant
      mutants. The variant complexes all showed weaker binding than wild-type RT, while
      giving rise to similar, but critical changes in the protein. Therefore, the
      design of new inhibitors should center on obtaining stronger binding drugs to key
      drug-resistant RT variants.

PMID- 9543001
TI  - Development of a structural model for the cytoplasmic domain of an integrin.
AB  - The cytoplasmic tails of integrin heterodimers play central roles in controlling
      the activation states of integrins and in transmitting intracellular signals.
      Despite their short length, no structure of any integrin cytoplasmic domain has
      been determined. Therefore, molecular models for the cytoplasmic domain of
      alpha(IIb)beta3, the major platelet integrin, were generated, including models
      for the individual cytoplasmic tails, the binary alphaIIb-calcium complex, and
      the ternary alphaIIb-beta3-calcium complex. Structural analysis of circular
      dichroism spectra were compiled with data obtained from short homologous
      sequences within crystallized proteins, and with secondary structural predictions
      to develop starting models for each subunit. These models were subjected to a
      series of energy minimization and molecular dynamic simulations to generate final
      models. AlphaIIb was predicted to be ordered at its N-terminus and its C-terminus
      could accommodate a cation in a multicoordinated complex. The structure of beta3
      was dominated by a beta-turn at its NPXY motif (beta3 744-747). In docking of
      alphaIIb to different sites within beta3, the conformation of the beta3 juxta
      transmembrane (beta3 716-721) was greatly altered. This region was confirmed to
      be a conformational 'hot-spot' by circular dichroism. The conformational
      flexibility of this juxta-transmembrane region, which is highly conserved amongst
      integrins, is ideally located to regulate signaling.

PMID- 9543002
TI  - Identification of indispensable residues for specific DNA-binding in the
      imperfect tandem repeats of c-Myb R2R3.
AB  - The individual repeats, R2 and R3, of the minimum specific DNA-binding domain
      (R2R3) of c-Myb have very similar structures, with a helix-turn-helix variation
      motif, although their sequence identity in the tandem repeats is only 31%. From
      previous mutational and structural studies, the third helices in both repeats
      were shown to directly recognize the specific base sequence, PyAACG/TG. In order
      to elucidate the reason for the imperfection of the tandem repeats at amino acid
      positions other than the recognition helices, a series of R2R3 mutants was
      generated by swapping the helices and the N-terminus in R2 to those in R3.
      Consequently, the sequence composing the first helix of R2 was found to be
      essential for specific DNA-binding, in addition to the third recognition helix of
      R2. Further mutational studies revealed that the only indispensable residues in
      the first helix are Val103 and Val1O7, which are involved in the hydrophobic core
      of R2. These residues do not directly interact with the DNA, but they contribute
      to the correct formation of helix 1 and the characteristic packing of R2, which
      is slightly different from that of R3, and are required for specific base
      recognition through strong cooperativity with R3.

PMID- 9543003
TI  - A glutamine 67--> histidine mutation in homotetrameric R67 dihydrofolate
      reductase results in four mutations per single active site pore and causes
      substantial substrate and cofactor inhibition.
AB  - R67 dihydrofolate reductase (DHFR) is a type II DHFR produced by bacteria as a
      resistance mechanism to increasing clinical use of the antibacterial drug
      trimethoprim. Type II DHFRs are not homologous in either sequence or structure
      with chromosomal DHFRs. The crystal structure of R67 DHFR shows a single active
      site pore that spans the length of the homotetramer. Related sites (due to a 222
      symmetry element at the center of the pore) are used to bind ligands, i.e. each
      half of the pore can accommodate either the substrate, dihydrofolate (DHF), or
      the cofactor, NADPH, although DHF and NADPH are bound differently. To evaluate
      the role of glutamine 67 (and its symmetry-related Q167, Q267 and Q367 residues
      which occur at the center of the active site pore), a Q67H mutation was
      constructed. Binary binding of dihydrofolate (DHF; monitored by isothermal
      titration calorimetry) displays two identical sites with a Kd value of 0.04
      microM, while binding of NADPH shows two sites possessing negative cooperativity
      with Kd values of 0.027 and 0.62 microM. A comparison of ligand binding in Q67H
      versus wild-type (wt) R67 DHFR indicates both ligands bind more tightly (80-6000
      fold) and DHF binding in Q67H R67 DHFR no longer displays positive cooperativity
      as seen in wt R67 DHFR. Ternary complex binding in the Q67H mutant indicates a
      total of two ligands can bind per pore. Substantial substrate and cofactor
      inhibition are observed during catalysis, consistent with non-productive binding
      of either two DHF or two NADPH molecules in Q67H R67 DHFR. Because of the
      symmetry-related binding sites in the active site pore, the accumulation of
      potentially positive mutations in R67 DHFR is limited by the balance between
      tighter binding of ligands (and thus potentially increased catalytic efficiency)
      and inhibition that arises upon tighter binding of two identical ligands at
      symmetry-related sites.

PMID- 9543004
TI  - Structural and functional roles of a conserved proline residue in the alpha2
      helix of Escherichia coli thioredoxin.
AB  - Proline 40 in Escherichia coli thioredoxin is located close to the redox active
      site (Cys32-Cys35) within the alpha2 helix. The conservation of this residue
      among most of the thioredoxins suggests that it could play an important role in
      the structure and/or function of this protein. We have substituted Pro40 for Ala
      by using site-directed mutagenesis and expressed the mutant P40A in E.coli. The
      effects of the mutation on the biophysical and biological properties of
      thioredoxin have been analyzed and compared with molecular dynamics simulations.
      Modeling predicted that the replacement of Pro40 by Ala induced a displacement of
      the active site which exposes Trp31 to the solvent and opens a cleft located
      between helices alpha2 and alpha3. The solvation free energy (SFE) calculation
      also indicated that P40A became more hydrophobic as W31 became more accessible.
      These predictions were totally in agreement with the experimental results. The
      mutant P40A exhibited chromatographic behavior and fluorescence properties very
      different from those of the wild-type (WT) protein, in relationship with the
      displacement of W31. The determination of the free energy of unfolding of P40A
      showed that the mutant was globally destabilized by 2.9 kcal/mol. However, the
      effect of the mutation on the transition curve was highly unusual as the midpoint
      of the unfolding transition increased, indicating that some local structures were
      actually stabilized by the mutation. Despite these structural modifications,
      neither the ability of the protein to reduce a chloroplastic enzyme nor its
      reactivity with the bacterial reductase decreased. The only functional difference
      was the higher stability of P40A in light activation of NADP-malate dehydrogenase
      under air, which suggests that the mutant was less rapidly re-oxidized than WT.
      Therefore, it can be concluded that Pro40 is not essential for maintaining the
      redox function of thioredoxin but rather is required for the stability of the
      protein.

PMID- 9543005
TI  - Spontaneous oligomerization of a staphylococcal alpha-hemolysin conformationally
      constrained by removal of residues that form the transmembrane beta-barrel.
AB  - Staphylococcal alpha-hemolysin is a water soluble, monomeric, bacterial exotoxin,
      which forms heptameric pores in membranes. The rate determining step in assembly
      is the conversion of a heptameric prepore to the fully assembled pore in which
      the central glycine-rich domain of each subunit inserts into the membrane to form
      a 14 strand beta barrel. Barrel formation is accompanied by a conformational
      change in which each N terminus latches onto an adjacent subunit. In the monomer
      in solution, the central domain is loosely organized and exposed to solvent. In
      this study, 25 amino acids of the central domain were removed and replaced with
      the sequence Asp-Gly, which favors the formation of a type I' beta-turn, to yield
      a mutant devoid of hemolytic activity. Within minutes after synthesis in the
      absence of membranes, the mutant polypeptide spontaneously assembled into
      heptamers, as demonstrated by atomic force microscopy. Limited proteolysis
      suggested that the N termini of the subunits in the heptamers were in the fully
      assembled pore conformation rather than the prepore conformation. Based on these
      findings, the deletion is proposed to constrain the central domain and thereby
      force the creation of a shortened beta barrel, which in turn induces the
      additional structural changes that normally accompany pore formation. The
      truncated pore might make a useful framework for the construction of designed
      membrane active macromolecules.

PMID- 9543006
TI  - Effects of sulfhydryl regents on the activity of lambda Ser/Thr phosphoprotein
      phosphatase and inhibition of the enzyme by zinc ion.
AB  - Sulfhydryl reagents, such as dithiothreitol (DTT), affected the activity of
      Ser/Thr phosphoprotein phosphatases. Addition of DTT to the assay buffer
      increased the affinity of lambda Ser/Thr phosphoprotein phosphatase (lambda
      PPase) for its Mn2+ cofactor. On the other hand, the enzyme was found to be
      inactivated simply by dilution in Tris buffer. The inactivation could be
      completely prevented by the presence of DTT or Mn2+ in the buffer. Further
      studies showed that oxidation or reduction of cysteine residues in lambda-PPase
      may not be the cause of the change in the enzyme activity. Without exception,
      mutation of all cysteine residues in lambda-PPase to serine did not convert the
      enzyme into a thiol-insensitive mutant. By careful examination of the effects of
      different sulfhydryl reagents, metal ion cofactors and substrates on lambda
      PPase, it was found that the role of sulfhydryl reagents was the chelation of
      small amounts of inhibitory metal ions, which were present in plastic laboratory
      ware, such as disposable cuvets and tubes, with prevention of the enzyme from
      inactivation. One of the main contaminants found in plastic cuvets was Zn2+,
      which is a potent inhibitor of lambda-PPase. The inhibition of lambda-PPase by
      Zn2+ was characterized. Pre-treatment of the enzyme (1-4 nM) with 1 microM of
      ZnCl2 almost completely inhibited the enzymatic activity in response to 2 mM
      Mn2+. However, no significant inhibition was found when the enzyme was added to
      the assay mixture containing 1 microM Zn2+ and 2 mM Mn2+ . This confirms the
      sensitivity of the holoenzyme to inhibitory metal ions in vitro. The kinetic
      analysis indicated that the inhibitory metal ion might compete with Mn2+ to bind
      to the active site of lambda-PPase. This was further supported by the mutation of
      metal cofactor binding amino acid residues of the enzyme. Mutants which have less
      affinity for Mn2+ are also less sensitive to Zn2+. Our results suggest that
      inhibitory metal ions may induce a different structural conformation for lambda
      PPase.

PMID- 9543007
TI  - A form of anti-Tac(Fv) which is both single-chain and disulfide stabilized:
      comparison with its single-chain and disulfide-stabilized homologs.
AB  - Disulfide-stabilized Fvs (dsFvs) are recombinant proteins composed of a heavy
      chain variable domain (VH) of an antibody connected via a disulfide bond to the
      light-chain variable domain (VL). In single-chain Fvs (scFvs), a peptide
      connector links VH and VL. The dsFv form of the anti-Tac monoclonal antibody
      which reacts with the alpha subunit of the IL2 receptor was recently reported to
      be more stable and to aggregate less during renaturation than anti-Tac(scFv). In
      addition, it could be produced in a better yield owing to less aggregation.
      However, the yields are still too low to permit the production of material for
      clinical trials in which the dsFv will be used to image or treat IL2 receptor
      (CD25)-containing tumors. To increase the efficiency by which VH and VL associate
      and form a disulfide bond during renaturation, we have prepared an Fv form of
      anti-Tac which is both single chain and disulfide stabilized (scdsFv). The
      recombinant protein is expressed in Escherichia coli, where it accumulates in
      inclusion bodies. Using inclusion body protein as the reference point, the yield
      of purified anti-Tac(scdsFv) was 13% compared with 2% for anti-Tac(dsFv). Anti
      Tac(scdsFv) has equivalent binding affinity, immunoreactivity after radiolabeling
      and stability. The results show that a linker between VH and VL facilitates
      heterodimer formation and leads to disulfide bond formation in a higher
      percentage of the molecules renatured. Thus anti-Tac(scdsFv) is the preferred
      form of anti-Tac(Fv) to be used for clinical studies. We anticipate that scdsFvs
      will be the optimum recombinant form of Fv to produce from bacteria.

PMID- 9543008
TI  - Purification and crystallization of complexes modeling the active state of the
      fragile histidine triad protein.
AB  - Fragile histidine triad protein (Fhit) is a diadenosine triphosphate (ApppA)
      hydrolase encoded at the human chromosome 3 fragile site which is frequently
      disrupted in tumors. Reintroduction of FHIT coding sequences to cancer cell lines
      with FHIT deletions suppressed the ability of these cell lines to form tumors in
      nude mice even when the reintroduced FHIT gene had been mutated to allow ApppA
      binding but not hydrolysis. Because this suggested that the tumor suppressor
      activity of Fhit protein depends on substrate-dependent signaling rather than
      ApppA catabolism, we prepared two crystalline forms of Fhit protein that are
      expected to model its biologically active, substrate-bound state. Wild-type and
      the His96Asn forms of Fhit were overexpressed in Escherichia coli, purified to
      homogeneity and crystallized in the presence and absence of ApppA and an ApppA
      analog. Single crystals obtained by vapor diffusion against ammonium sulfate
      diffracted X-rays to beyond 2.75 A resolution. High quality native synchrotron X
      ray data were collected for an orthorhombic and a hexagonal crystal form.

PMID- 9543009
TI  - Prion protein expression in Chinese hamster ovary cells using a glutamine
      synthetase selection and amplification system.
AB  - Syrian hamster prion protein (PrPC) and a truncated Syrian hamster prion protein
      lacking the glycosylphosphatidylinositol (GPI) anchor C-terminal signal sequence
      (GPI-) were expressed in Chinese hamster ovary cells using a glutamine synthetase
      selection and amplification system. The CHO cell clones expressing the GPI- PrP
      secreted the majority of the protein into the media, whereas most of the PrP
      produced by clones expressing the full-length protein with the GPI anchor was
      located on the cell surface, as demonstrated by its release upon treatment with
      phosphatidylinositol-specific phospholipase C (PIPLC). A cell clone that
      expressed the highest levels of full length PrP was subcloned to obtain clone
      30C3-1. PrP from clone 30C3-1 was shown to be sensitive to proteolysis by
      proteinase K and to react with monoclonal and polyclonal antibodies that
      recognize native PrPC. The recombinant PrP migrated as a diffuse band of 19-40
      kDa but removal of the N-linked oligosaccharides with peptide N-glycosidase F
      (PNGase F) revealed three protein species of 19, 17 and 15 kDa. The 19 kDa band
      corresponding to deglycosylated full-length PrP was quantified and found to be
      expressed at a level approximately 14-fold higher than that of PrPC found in
      Syrian hamster brain.

PMID- 9543010
TI  - Analysis of constitutive heterochromatin of Aotus (Cebidae, Primates) by
      restriction enzyme and fluorochrome bands.
AB  - The current classification of genus Aotus includes nine species, four of which
      occur above the Amazon River and five below it. The position of several of these
      taxa as a valid species has been questioned. Recently, we described the
      chromosomal constitution of a population in the state of Rondonia, Brazil, whose
      karyotype typically presented a considerable accumulation of constitutive
      heterochromatin. To best characterize these heterochromatins, in this work we
      subjected the metaphases of these animals to banding using AluI, HaeIII, HinfI,
      RsaI, DdeI, MboI and MspI restriction enzymes and CMA3 and DAPI fluorochromes.
      The banded metaphases were also submitted to sequential C-banding. RsaI, DdeI and
      MboI enzymes showed, in all chromosomes, a banding pattern of C type, similar to
      that obtained using barium hydroxide. This banding was also seen with AluI, HinfI
      and MspI, but with reduction or elimination of the C-bands in the chromosome
      pairs 1, 3-7 and 9. MspI also reduced the C-band of pairs 11, 16-21 and 23.
      HaeIII induced intermediate bands between G and C. Considering the data of the
      different bands produced, it was possible to characterize at least three distinct
      types of constitutive heterochromatin in Aotus from Rondonia: (a) centromeric
      bands, (b) bands of the heterochromatic short arms and (c) interstitial bands.

PMID- 9543011
TI  - Molecular cloning of metaphase chromosome protein 1 (MCP1), a novel human
      autoantigen that associates with condensed chromosomes during mitosis.
AB  - Systemic lupus erythematosus autoantibodies were used to identify and to
      characterize new human chromosome-associated proteins. Previous
      immunolocalization studies in human and murine tissue culture cells showed that
      some of these monoclonal antibodies recognize nuclear antigens that associate
      with condensed chromosomes during mitosis. One antibody was selected for
      screening a human HeLa S3 cDNA expression library, and cDNAs that code for an
      antigen of 31-33 kDa were isolated. Immunological, biochemical and cell
      fractionation data indicate that the 31- to 33-kDa antigen corresponds to the
      chromosome-associated protein recognized by the original monoclonal antibody.
      Sequence analysis shows that we isolated a novel human gene. Immunolocalization
      to human tissue culture cells shows that during interphase the antigen is
      dispersed in the nucleus and that during mitosis it associates exclusively with
      condensed chromosomes. A similar pattern of localization was also observed in
      mouse fibroblasts, suggesting that the antigen is conserved among different
      species. Finally, we show that part of the antigen remains bound to the
      scaffold/matrix component, even after high salt extraction.

PMID- 9543012
TI  - Chromosomal localization and distribution of simple sequence repeats and the
      Arabidopsis-type telomere sequence in the genome of Cicer arietinum L.
AB  - We used fluorescence in situ hybridization to probe the physical organization of
      five simple sequence repeat motifs and the Arabidopsis-type telomeric repeat in
      metaphase chromosomes and interphase nuclei of chickpea (Cicer arietinum L.).
      Hybridization signals were observed with the whole set of probes and on all
      chromosomes, but the distribution and intensity of signals varied depending on
      the motif. On root-tip metaphase chromosomes, CA and GATA repeats were mainly
      restricted to centromeric areas, with additional GATA signals along some
      chromosomes. TA, A and AAC repeats were organized in a more dispersed manner,
      with centromeric regions being largely excluded. In interphase nuclei of the
      inner integument, CA and GATA signals predominantly occurred in the
      heterochromatic endochromocentres, whereas the other motifs were found both in eu
      and heterochromatin. The distribution of the Arabidopsis-type telomeric repeat
      (TTTAGGG)n on metaphase chromosomes was found to be quite exceptional. One major
      cluster of repeats was spread along the short arm of chromosome B, whereas a
      second, weaker signal occurred interstitially on chromosome A. Only faint and
      inconsistent hybridization signals were visualized with the same probe at the
      chromosomal termini.

PMID- 9543013
TI  - Germ cell restriction and regular transmission of an accessory chromosome that
      mimics a sex body in the zebra finch, Taeniopygia guttata.
AB  - Mitotic and meiotic analysis with light and electron microscopy was performed in
      male and female zebra finches (Taeniopygia guttata). Somatic cells from bone
      marrow have a 2n = 80 and show the usual sex chromosome mechanism of birds ZZ
      (male)/ZW (female). In the germ lines of both sexes, a single accessory
      chromosome was regularly present in all the cells examined from all the
      individual birds. In synaptonemal complex (SC) spreads of pachytene oocytes and
      spermatocytes, this accessory chromosome forms a single axis, but it behaves
      differentially in male and female meiosis. While this accessory chromosome is
      euchromatic in oocytes, it is strongly heterochromatic in spermatocytes. In
      pachytene spermatocytes, the accessory chromosome adopts a morphology strikingly
      similar to that of the XY body ('sex vesicle') of mammalian spermatocytes. This
      accessory chromosome is eliminated during male meiosis and forms a cytoplasmic
      dense body in young spermatids that shows strong fluorescence with DAPI. The
      presence of this germ line-restricted chromosome does not affect the behaviour of
      the ZW pair in oocytes, as the sex chromosomes pair regularly and show a
      localized recombination nodule. It is suggested that this accessory chromosome
      has transcriptional activity during oogenesis, and thus it is regularly
      transmitted through preferential segregation during female meiosis.

PMID- 9543014
TI  - Chromosome stability is maintained by short intercentromeric distance in
      functionally dicentric human Robertsonian translocations.
AB  - While the formation of a dicentric chromosome often leads to chromosome
      instability, human dicentric Robertsonian translocations usually remain stable.
      To investigate the basis for this stability, we have examined the centromeres of
      15 structurally dicentric rob(13q14q) Robertsonian translocations using
      immunofluorescence and fluorescence in situ hybridization (FISH). The
      immunofluorescence detection of centromere protein C (CENP-C) was used as a
      marker for centromere function as CENP-C seems to play an essential role in
      kinetochore structure and stability and was previously shown to be absent from
      inactive centromeres. In all 15 translocation-containing cell lines, CENP-C was
      confined to only one of the centromeres of the translocation in a fraction of the
      cells analyzed. This suggests that centromere inactivation commonly occurs on
      dicentric Robertsonian translocations and may serve as one mechanism allowing for
      their stability. However, in the majority of the translocations (12 out of 15), a
      portion of the cells analyzed displayed CENP-C immunofluorescence at both
      centromeres, suggesting that both centromeres were active and that the
      translocation was functionally dicentric. The percentage of cells with CENP-C at
      both centromeres ranged from 2% to 82%. These results support the hypothesis that
      the close proximity of two functional centromeres on Robertsonian translocations
      allows them to remain stable.

PMID- 9543015
TI  - Relevance of kinetochore size and microtubule-binding capacity for stable
      chromosome attachment during mitosis in PtK1 cells.
AB  - Chromosomes attach to the mitotic spindle via their kinetochores. The average
      number of spindle microtubules binding to each kinetochore varies with species,
      the stage of mitosis, and the length of time that the kinetochore has been
      attached to the spindle. In this report, we investigate how kinetochore
      microtubule number varies with kinetochore size and chromosome size in PtK1
      cells. From an analysis of serial-section electron micrographs, we determined
      that the average surface area of metaphase, taxol-treated metaphase, and anaphase
      kinetochores is 0.16 +/- 0.05 microm2 (N = 181). Surprisingly, kinetochore
      microtubules are packed more densely on the smaller kinetochores, as seen by a
      reduction in the average spacing between kinetochore microtubules from 89 nm to
      59 nm. Our interpretation of this result is that PtK1 cells require a minimum
      kinetochore microtubule-binding capacity for survival during repeated rounds of
      mitotic division. We estimate the lower limit to be 23 kinetochore microtubules
      and suggest that this capacity is required to ensure stable attachment during the
      dynamic and highly stochastic process of kinetochore fiber formation. There is a
      modest but statistically significant increase in kinetochore microtubule number
      with chromosome size, indicating that chromosome size is a minor determinant of
      kinetochore microtubule number.

PMID- 9543017
TI  - The X1X2Y sex chromosome system in the fish Hoplias malabaricus. II. Meiotic
      analyses.
AB  - The neotropical fish Hoplias malabaricus shows diversified cytotypes and may
      represent a group of distinct species. One of these cytotypes is characterized by
      2n = 40 and 2n = 39 chromosomes in females and males, respectively, with a
      multiple sex chromosome system of the X1X1X2X2/X1X2Y type. The Y, representing a
      large chromosome in male karyotype, is derived from a translocation event between
      two biarmed chromosomes: one of them similar to X1 chromosome (no. 6) and another
      one similar to X2 chromosome (probably no. 20). Meiotic data (standard and
      synaptonemal complexes analyses) show 18 bivalents and one characteristic
      trivalent in pachytene and metaphase I spermatocytes, as well as two kinds of
      metaphase II cells with 19 and 20 chromosomes. The trivalent is formed by the Y,
      X1 and X2 chromosomes and usually presents a complete pairing in pachytene.
      However, trivalents with partially or fully asynapsed segments are also observed.
      These segments are assumed to be non-homologous regions of the X1 and X2
      chromosomes without correspondence with the Y chromosome, which can
      heterosynapse. This behaviour of the sex trivalent leading to a fully paired
      structure, taken together with the close frequencies of the two spermatocyte
      types at metaphase II, suggests a normal pattern for male H. malabaricus meiosis,
      representing a stabilized multiple sex chromosome system in this species.

PMID- 9543016
TI  - Nucleotide specificity at the boundary and size requirement of the target sites
      recognized by human centromere protein B (CENP-B) in vitro.
AB  - Human centromere protein B (CENP-B) has a sequence-specific DNA binding activity.
      We previously reported several CENP-B binding motifs by analysing synthetic
      oligonucleotides as well as alphoid DNA isolated from the human genomic library.
      Here, we examined the size requirement and nucleotide specificity of human CENP-B
      binding sequences in vitro. We synthesized three sets of mixed oligonucleotides
      containing diverged authentic binding sites (CTTCGTTGGAAACGGGA) in which certain
      pairs of nucleotides (underlined) were degenerated. Each oligonucleotide with a
      defined sequence was separately introduced into a plasmid and mixed with GST
      fused recombinant CENP-B. The DNA-protein complex formed was affinity purified
      with glutathione Sepharose. Any nucleotide substitutions at the positions 1, 2
      and 17 did not significantly influence the recovery, while the substitutions at
      positions 3, 4 and 16 did, suggesting that the internal 14-bp motif
      (TCGTTGGAAACGGG) constituted the minimum requirement. However, it showed a lower
      affinity to CENP-B, compared with the authentic motif. The inclusion of T at the
      5' end greatly increased the affinity, and the further addition of A or T at the
      3' end (TTCGTTGGAAACGGGA/T) offered affinity similar to the authentic motif. The
      first nucleotide of the 17-bp authentic binding motif may not be essential for
      CENP-B binding.

PMID- 9543018
TI  - Rights and welfare of incapable adults: advocacy, ethics and the law.

PMID- 9543019
TI  - Eradication of poliomyelitis is on track in the WHO European and Eastern
      Mediterranean regions.

PMID- 9543020
TI  - Stop exporting tobacco madness.

PMID- 9543021
TI  - Aspirin treatment.

PMID- 9543023
TI  - The hidden waiting lists--older people denied care.

PMID- 9543022
TI  - Midwives and woman-centred care.

PMID- 9543024
TI  - Clinical effectiveness can be routine, says King's Fund.

PMID- 9543025
TI  - Primary and secondary interface for mental healthcare.

PMID- 9543026
TI  - HAS 2000.

PMID- 9543027
TI  - Healthcare inadequate according to MS society.

PMID- 9543028
TI  - Recommendations for psychiatrists working with recovered memories of child sexual
      abuse.

PMID- 9543029
TI  - Cultural safety: a new concept in nursing people of different ethnicities.
AB  - Cultural safety is a concept which has been developed by Maori nurses in New
      Zealand in order to reflect on nursing practice from their point of view as the
      indigenous minority in our country. The paper contrasts this new concept
      critically with Leininger's well-known model of transcultural nursing in order to
      suggest its potential significance. To date work on cultural safety in New
      Zealand has focused on the attitudes which individual nurses bring to their
      practice, attempting to change the effects of their social conditioning on their
      approach to nursing. The paper supports the view that all nursing care is
      provided in a social context which influences its efficacy, and specifies that
      the structural elements, such as the institutional context within which nursing
      care is provided and policies which influence how care is the provided, need to
      be explicitly recognized. The paper concludes that until the effects on the
      health care system of inequalities in power between groups in society are
      addressed we cannot ensure that the needs of persons from minority cultures will
      be met. Because it illuminates this dimension of nursing care, cultural safety is
      a concept of general significance for all nurses.

PMID- 9543030
TI  - Relationships between infant temperament, demographic variables, and family
      dynamics of childrearing families.
AB  - Relationships between infant temperament, demographic variables, and family
      dynamics of child-rearing families were investigated in this study. The revised
      Infant Temperament Questionnaire (RITQ), the Family Dynamics Questionnaire (FDQ)
      and the Family Dynamics Measure (FDM) were sent to 118 families who had
      participated in the first stage of the study as child-bearing families. About 8
      months after childbirth 96 mothers and 95 fathers completed the questionnaires.
      The characteristics of infant temperament and demographic variables related to
      the variance of dimensions of family dynamics. Characteristics of the
      temperamentally easy baby related to more positive family dynamics perceived by
      child-rearing parents. Fathers rearing their first child reported that their
      families functioned better than fathers with their second infant. In child health
      clinics families rearing their second child should also be supported, especially
      families with arrhythmic and negative mood infants.

PMID- 9543031
TI  - Relaxation techniques for acute pain management: a systematic review.
AB  - This review aims to document the effectiveness of relaxation techniques, when
      used alone for the management of acute pain, after surgery and during procedures.
      A systematic review of randomized controlled trials (RCTs) was undertaken. Seven
      studies involving 362 patients were eligible for this review. One hundred and
      fifty patients received active relaxation as the sole intervention. Reports were
      sought by searching MEDLINE, psycLIT, CINAHL, and the Oxford Pain Relief
      Database. The outcome measures used were pain and psychological factors. A meta
      analysis was not possible, due to lack of primary data. Three of the seven
      studies demonstrated significantly less pain sensation and or pain distress in
      those who had relaxation. Four studies did not detect any difference. There was
      some weak evidence to support the use of relaxation in acute pain. However, this
      was not conclusive and many of both the positive and the negative studies
      suffered from methodological inadequacies. Well designed and executed randomized
      controlled trials are needed before the clinical use of relaxation in acute pain
      management can be firmly underpinned by good quality research evidence. Until
      this evidence is available we recommend that the clinical use of relaxation in
      acute pain settings is carefully evaluated and not used as the main treatment for
      the management of acute pain.

PMID- 9543032
TI  - Relaxation for the relief of chronic pain: a systematic review.
AB  - The effectiveness of relaxation techniques in the management of chronic pain was
      determined in this systematic review of published randomized controlled trials.
      Reports were sought by searching MEDLINE, psycLIT, CINAHL, EMBASE and the Oxford
      Pain Relief Database. Studies were included in this review if they were
      randomized controlled trials of relaxation techniques in chronic pain. Studies
      which investigated the effects of relaxation in combination with other
      interventions were not considered. Nine studies involving 414 patients met the
      predefined inclusion criteria and are critically appraised in this review. Meta
      analysis was not possible, due to lack of quantitative data in the primary
      studies. Studies involved patients with a range of chronic pain conditions. The
      McGill Pain Questionnaire was the most common pain outcome used. Whilst four
      studies were able to show a significant difference for the pain outcomes in
      favour of relaxation for the pre- and post-treatment assessments, few
      statistically significant differences were reported in favour of relaxation when
      between treatment comparisons were used. Only three studies reported
      statistically significant differences in favour of relaxation (judged as a
      significant difference for at least 1 of the pain outcomes) compared to the other
      treatment groups. In rheumatoid arthritis the McGill Pain Questionnaire scores
      were significantly lower for patients receiving relaxation compared to those who
      were in the routine treatment control group. In ulcerative colitis significant
      differences were reported for six of seven different pain outcome measures in
      favour of progressive muscle relaxation compared to patients in the waiting list
      control group. In one of the two cancer pain studies, relaxation taught by nurses
      produced significantly lower pain sensation scores compared to the control group.
      Two studies reported significant differences in favour of the experimental
      control groups rather than for relaxation. There is insufficient evidence to
      confirm that relaxation can reduce chronic pain. Many of the studies both
      positive and negative suffer methodological inadequacies. Recommendations for
      future research into the effectiveness of relaxation techniques for chronic pain
      are made.

PMID- 9543033
TI  - Investigating psychosocial aspects of participation in early anti-cancer drug
      trials: towards a choice of methodology.
AB  - This paper presents the methodological approach and research methods chosen to
      explore psychosocial aspects of participation in early anti-cancer drug trials
      from the perspective of those actually involved. The paper describes how an
      appropriate methodology, or principles of reasoning behind the choice of research
      methods, emerged. The choice of methodology was based on three elements: first,
      an understanding of the competing philosophies about how research can be
      approached and conducted; second, the author's view of the subject area; and
      third, a consideration of previous research approaches which have investigated
      psychosocial aspects of cancer clinical trials. A qualitative methodology
      situated within an interpretative paradigm was eventually chosen as the most
      appropriate means of exploring trial participants' experiences and the aim and
      objectives of the research were developed within this methodological framework.

PMID- 9543034
TI  - The co-existence of psychiatric disorders and substance misuse: working with dual
      diagnosis patients.
AB  - The co-existence of substance misuse and psychiatric disorders is often referred
      to by the term 'dual diagnosis'. The health-related problems associated with dual
      diagnosis has received growing attention by clinicians and researchers alike.
      Severely mentally ill patients who misuse drugs (prescribed and illicit) or
      alcohol have complex health and social needs. Mental health nurses have a key
      role to play in the early recognition and management of this group of patients.
      This paper examines the nature and extent of dual diagnosis and its implications
      for mental health nurses. It also addresses treatment strategies that are
      required to meet the needs of this cohort of patients.

PMID- 9543035
TI  - Developing a non-aversive intervention strategy in the management of aggression
      and violence for people with learning disabilities using natural therapeutic
      holding.
AB  - This paper builds upon a previous piece of research regarding the development of
      'natural therapeutic holding' as a non-aversive alternative to control and
      restraint (C and R) in managing aggression and violence in people with learning
      disabilities. This paper represents aspects of an ongoing programme of research
      and explains the aims and values which underpin natural therapeutic holding by
      describing the theory, aims, values and practical application. The concepts of
      individual risk management and pro-active intervention strategies are discussed
      with illustrations of practical application given by means of a case study. The
      case study shows that over a relatively short period of time, an individual with
      severe learning disabilities who is aggressive and violent, learns alternative
      coping strategies to aggression and violence through the application of natural
      therapeutic holding. The article concludes that natural therapeutic holding is a
      very effective intervention strategy in the management of violence in people with
      learning disabilities from two perspectives: (a) it provides staff with safe,
      professional and ethical skills with which they can manage aggressive and violent
      clients and (b) as a therapy, natural therapeutic holding gives clients the
      opportunity to learn coping strategies which are more effective than violence.

PMID- 9543036
TI  - The contexts for managing depression and its stigma among black West Indian
      Canadian women.
AB  - There is a paucity of literature available to assist nurses and other care
      providers in knowing how to meet the needs of depressed women from non-dominant
      cultural backgrounds. To begin to address this need, we conducted a grounded
      theory study on black West Indian Canadian Women's strategies for managing
      depression. We discovered a basic social process, Being Strong, that the women
      used to manage or ameliorate depression. Being strong occurs within the
      overlapping areas of three social contexts: the cultural stigma of depression,
      male-female roles and relationships, and belief in Christian doctrine. These
      contexts are located against a backdrop of visible minority status within a
      eurocentric society. This socio-cultural contextual material provides the setting
      within which black West Indian Canadian women live and make decisions. In this
      article, we present findings related to the social and cultural aspects of the
      women's situation.

PMID- 9543037
TI  - Stress and the intensive care patient: perceptions of patients and nurses.
AB  - This study was a replication of an earlier Cochran & Ganong study that
      investigated the perception of nurses and patients regarding the stressors faced
      by patients in the intensive care unit environment. As the original study was
      American in origin, one of the aims of the present study was to discover if the
      results would be replicated in a United Kingdom (UK) intensive care unit. Data
      collection was by the use of an environmental stress questionnaire that was an
      adaptation of the original data collection tool modified for use in a UK
      intensive care unit. The study was undertaken in two intensive care units
      producing a sample size of 71 patients and 71 nurses. There appears to be a wide
      variation in the perception of nurses and patients regarding the stress faced by
      patients in the intensive care unit. Similarities were noted between subject
      groups as to the nature of the stressors, although nurses tended to rate items
      over which they believed they had control as being more stressful than did the
      patients. Patients tended to rate items related to their illness and physical
      comfort as being most stressful. The results are in keeping with those from the
      Cochran & Ganong study.

PMID- 9543038
TI  - The influence of psychological factors on the self-management of insulin
      dependent diabetes mellitus.
AB  - This study investigated the influence of a number of psychological factors upon
      the practice and outcome of diabetic self-management among young adults with
      insulin-dependent diabetes mellitus. Health beliefs, perception of control and
      knowledge were assessed by scales and questionnaires and glycosylated haemoglobin
      results and clinic attendance records obtained for 263 patients. The results
      demonstrated that the sample members perceived that they were responsible for the
      control of their diabetes, that the benefits of following treatment were greater
      than any barriers and that they were knowledgeable about their diabetes. However,
      these factors were not predictive of the outcome variables of metabolic control
      or clinic attendance according to multiple regression analysis. Implications of
      these results for nursing practice and for future research are discussed.

PMID- 9543039
TI  - Successive surveys of an expert panel: research in decision-making with health
      visitors.
AB  - A United Kingdom expert panel was consulted to develop a self-completion
      instrument for research on decision making in health visiting practice. The use
      of a Delphi-type technique demonstrated how a stand-alone postal survey was an
      insufficient measure for health visitors, requiring a supplementary follow-up
      method to study types of casework. A review of literature raised questions about
      the significance of intuitive thinking and reasoning in health visitor practice,
      in relation to measuring professional service and individual performance.

PMID- 9543040
TI  - Working with team midwifery: health visitors' views of one team midwifery scheme.
AB  - The fragmented nature of maternity services in the UK has led to the introduction
      of various forms of team midwifery scheme. The aim of such schemes is usually to
      increase continuity through the provision of antenatal, intrapartum and postnatal
      care to women by a small team of midwives. Few published studies of this
      organization of midwifery care exist, and even fewer consider the impact of such
      schemes on related health professionals. This paper presents the results of an
      independent survey of health visitors working alongside one team midwifery scheme
      in the south-east of England. Eighty per cent of the health visitors thought that
      team midwifery was a good idea in theory; however, just 27% thought it was
      working well locally and 70% reported that they would like to go back to working
      in the way they did before the introduction of team midwifery. The survey
      highlighted the health visitors' concerns in relation to team midwifery locally.
      Two issues were paramount: firstly a reported deterioration in interdisciplinary
      communications, and secondly a perceived loss of continuity for the women. Thus
      team midwifery, as implemented in this locality, may not attain the goals aimed
      at by the organization of care in this way.

PMID- 9543041
TI  - Nursing assessments in New Zealand mental health.
AB  - During 1992 a new Mental Health Act was implemented in New Zealand. The Act
      created a new role, that of the duly authorised officer (DAO) which has been
      mainly carried out by community mental health nurses. During 1994 a multisite
      qualitative research study was undertaken to describe the newly structured mental
      health nursing role and examine the issues related to it. A key issue which
      emerged was the concern that the nursing role had been defined and resourced by
      other groups (legal, medical and management) on the basis of its visible tasks
      rather than the invisible components of professional nursing knowledge and
      expertise. The legal descriptions of the DAO role negated the highly developed
      assessment skills of mental health nurses, suggesting that nurses are there for
      advice and assistance. Yet expert clinical judgement was pivotal to the effective
      functioning of the new role. This paper argues that the initial nursing mental
      health crisis assessment which is carried out in the community is a highly
      skilled nursing activity which must be recognized and resourced accordingly.

PMID- 9543042
TI  - Getting going with clinical supervision: an introductory seminar.
AB  - Clinical supervision is an emerging force in nursing practice in the United
      Kingdom. However, much of the nursing literature suggests uncertainty with
      regards to what clinical supervision is and the resources needed for safe
      professional practice. This paper explores a method of introducing clinical
      supervision to nurses in such a way as to model the skills and competencies
      required for developing productive working relationships. The main recommendation
      of this paper is that procedures for introducing clinical supervision mirror
      qualities required for developing effective nursing relationships.

PMID- 9543043
TI  - Living with high blood pressure.
AB  - This study was undertaken to explore the experience of people taking long-term
      antihypertensive medication. The study contributes to the understanding health
      professionals have of people with high blood pressure and the antihypertensive
      treatments they receive. Consideration was given to the full life context of
      people taking long-term antihypertensive medication and the health/medical
      culture in which people find themselves. A qualitative method of inquiry
      generated the descriptive data. Nineteen participants (four men and 15 women)
      were interviewed once, of which 16 were interviewed a second time. Data analysis
      involved extraction of concepts which in turn were clustered into themes. An
      organizing framework was constructed to integrate the six themes and 18 sub
      themes. The framework represents the individual's experience as a sequence,
      starting broadly in the social context of her/his life, and narrowing down to the
      particulars of personal routine and patterns referring to living with
      hypertension and it's medication regimens. The final theme refers to the broader
      context of the health culture. A vast range of experiences were described by
      participants taking long-term antihypertensive medication. This accentuates the
      necessity for health professionals to address the uniqueness of the individual,
      and consider the context of a person's life when prescribing and monitoring
      medications for people with high blood pressure.

PMID- 9543044
TI  - Interviewing older people by telephone following initial contact by postal
      survey.
AB  - Although the use of the telephone for interviewing has become a commonly used and
      largely accepted research method, the literature on this subject makes it clear
      that certain reservations remain. Some of these relate to problems encountered
      when interviewing older adults by telephone and others concern the use of the
      telephone in interviews where there has been no prior face-to-face contact. The
      conclusions of others who have studied these two sets of problems in combination
      are that special difficulties exist. These conclusions are examined with
      reference to researchers' experiences of conducting a study on continence care,
      in which a postal survey (as opposed to face-to-face contact) preceded telephone
      interviews. Interviews were conducted with adults of all ages, including a high
      proportion of older people. Researchers encountered few major difficulties and
      were satisfied with both response rate and response quality. Research to compare
      the effects of a variety of initial contact modes on telephone interviews with
      both younger and older adults is recommended.

PMID- 9543045
TI  - A model of professional nurse caring: nursing students' experience.
AB  - Research into caring from the perspective of nursing students is poorly
      documented. This paper presents a study which described the construct of caring
      as experienced by students in pre-registration programmes at two universities in
      New South Wales, Australia. Qualitative data were collected using a questionnaire
      and semi-structured interviews. From the analysis of the data a model of
      professional nurse caring from the student's perspective was created. In this
      model, compassion, as the core of caring is actualized in the students' nursing
      of patients by communicating, providing comfort, being competent, being
      committed, having conscience, being confident and being courageous. Communication
      is not only an actualization of this caring but constitutes an important medium
      for the expression of caring actions.

PMID- 9543046
TI  - Empirically generated attributes of experience in nursing.
AB  - Researchers examining clinical decision-making often explored the role of the
      nurse's experience. In these studies, experience was conceptualized as either the
      time spent in nursing or the knowledge which came from practice. This paper
      reports on the conceptualization of the nurse's experience emerging from a
      grounded theory study describing one decision-making process: 'knowing the
      patient'. Data included in-depth interview text, participant observation
      fieldnotes, and documents. Data were analysed using the constant comparative
      method and open, axial and selective coding techniques. In the analysis, the
      nurse's experience was conceptually defined as 'the application of that learned
      from previous practice situations'. Three attributes of the nurse's experience
      emerged. These included a focus on the patient, confidence in practice, and
      knowledge of antecedents and consequences of similar patient situations. Each
      aspect enhanced the individualization of nursing interventions. The findings are
      related to other investigations in nursing and insights for practice are offered.

PMID- 9543047
TI  - Self-efficacy as a predictor of academic performance in science.
AB  - Nursing students have traditionally experienced difficulties with the science
      subjects in nursing curricula, and irrespective of the institution conducting a
      nursing programme, this trend appears to be continuing. A satisfactory means of
      predicting academic performance in these subjects will facilitate the development
      of educational strategies designed to assist students overcome their
      difficulties. In this study, an instrument called the Self-Efficacy for Science
      (SEFS) was developed and tested. The SEFS was designed to predict academic
      performance in the science areas of a first-year undergraduate nursing course. A
      cohort of first-year students enrolled in a bachelor of nursing course were
      surveyed by questionnaire. Students' academic scores for two first-year science
      subjects were obtained and used as the criterion measure for the study. Principal
      component factor analysis revealed the SEFS contained six instead of the
      hypothesized four factors. These six factors could explain 70% of students' self
      efficacy for science. Cronbach alpha of the SEFS was 0.9. The SEFS could predict
      24% of the cohort's academic performance in a physical science subject and 18.5%
      for a bioscience subject. Studying science in the final year at high school was
      not statistically significantly related to the SEFS. Implications for students
      and future research are discussed.

PMID- 9543048
TI  - Non-English speaking background high school students' attitudes towards the
      nursing profession.
AB  - Australia is a multicultural nation with its population coming from over 120
      different cultural backgrounds. With the arrival of new immigrants from Southeast
      Asia, China, Korea and Lebanon over the last 20 years, issues such as the
      recruitment of bilingual and cross-cultural knowledgeable nurses have become a
      high priority within the health care system. However, recruiting these skilled
      professionals has been difficult. This study aimed to examine (1) non-English
      speaking background (NESB) high school students' career preferences in relation
      to nursing; and (2) whether nursing is perceived differently by the Korean,
      Lebanese, Vietnamese and mainland Chinese high school students. A convenience
      sample of 162 NESB high school students with parents from Korea, Lebanon, Vietnam
      and China was recruited from Sydney, New South Wales, Australia. Data were
      collected by a questionnaire to measure students' knowledge about, attitudes
      towards and intention to study nursing and their demographic details. Descriptive
      and inferential statistics were used to describe students' demographic
      background, their career preference and to compare knowledge, attitudes and
      intention scales among the NESB groups. Results indicated that less than 10% of
      students included nursing among their preferred career options. Korean students
      scored lower than the other NESB groups on attitude and intention towards
      nursing. The findings provide clues as to how nursing can be better promoted to
      NESB school leavers. Limitations of the study were discussed and recommendations
      were suggested for future research.

PMID- 9543049
TI  - The role of personal tutor in nurse education: towards an understanding of
      practice in a college of nursing and midwifery at a particular point in time.
AB  - This paper describes an inquiry to increase understanding of the role of personal
      tutor in a college of nursing and midwifery. Concepts of tutor and role are
      discussed in relation to their historical influences and an over view is provided
      of the research process which included document analysis and reflective audio
      taped interviews with student nurses, teachers and education managers. Five
      conceptual categories are identified and critically analysed in relation to
      personal, institutional and social contexts and the factors which influence them.
      The first two categories identified reflect the concepts discussed in the
      literature. The third category reflects the uncertainties and confusion which
      surround differing perceptions of the role. The fourth category suggests the
      misunderstandings which may occur through taking for granted apparently shared
      concepts. The fifth category suggests the significance of personal theory in
      practice and the extent to which roles are taken or made. Traditional values
      concerning theory and practice are thus challenged. The reflective evidence
      provided by the participants suggests a theory, generated by them through the
      meanings they give to their views and actions, concerning their roles and the
      situation in which they find themselves at a particular point in time.

PMID- 9543050
TI  - The use of professional nursing practice standards in nursing labour arbitrations
      in British Columbia, 1987-1994.
AB  - This study examined the use of nursing practice standards in British Columbia in
      labour arbitrations related to patient care for the years 1987-1994.
      Retrospective secondary content analysis was the method used to analyse the
      cases. Although practice standards were referred to in some of the cases, the
      nature and clarity of these standards were not always evident. In addition,
      corporate and industrial precedents, rather than health care precedents, formed
      the basis for much of the arbitration deliberations. The perspectives of nurses,
      patients, and families were not significantly represented. Many of the
      arbitration hearings did not get beyond procedural matters, and so did not
      address substantive patient care situations. Clearly, the visibility and
      importance of nursing standards need to be raised among nurses and non-nurses
      alike. Implications and recommendations for nursing practice, administration,
      education and research, as well as for nursing professional associations and
      unions are discussed. Research questions for the future are suggested.

PMID- 9543051
TI  - Backs to the future? Reflections on women, ageing and nursing.
AB  - There is now a certain amount of evidence to support the contention that ageism
      is not only rife amongst the population at large, but also amongst many of those
      who care for older people in a professional capacity. Given that many of these
      professionals are women caring for other women -- and nursing is a prime example 
      - this should at the very least give us serious cause for concern. This paper
      explores the relationship between 'ageing women' and 'old women' from the point
      of view of personal and professional attitudes and practices. It examines the
      proposition that until we, as women, fully explore and understand our own
      attitudes towards ageing and old age, we cannot work in ways which are truly
      beneficial and empowering for the older women in our care. The purpose of the
      paper is threefold. First, it reviews what is a relatively limited body of
      literature and research on this topic. Second, it reports on the preliminary
      findings from an exploratory study examining the attitudes of female nurses to
      their own ageing. Finally, it reflects further on the issues raised and considers
      some of the ways in which we can begin to address and confront the challenges
      which being 'ageing women' and 'aged women' in late 20th century Britain
      presents.

PMID- 9543052
TI  - Student nurses' lived experience of the sudden death of their patients.
AB  - This phenomenological study looks at the lived experience of third-year student
      nurses caring for dying patients in surgical, medical and elderly care units.
      Informal interviews were tape recorded and interpretive analysis was applied to
      narrative accounts of the nursing students' experiences. Themes which emerged
      from the students' narrative accounts included sudden death experience,
      vulnerability and support. These are evaluated in terms of their meaning for
      students and the possible implications for clinical care. In addition, the use of
      students' narratives is also suggested as a valuable learning tool both within
      clinical and academic frameworks.

PMID- 9543053
TI  - The work of clinical nurse specialists (HIV/AIDS) in areas with a low prevalence
      of HIV infection.
AB  - The role of the clinical nurse specialists (HIV/AIDS) who work in areas with a
      low known prevalence of HIV is considered and their contribution to patient care,
      either directly or indirectly through the education and support of other health
      care workers, is discussed. Attention is given to the implications for nursing
      practice and the role of the clinical nurse specialist associated with the
      relative infrequency of contact with patients who have HIV disease; and some of
      the issues for people living with HIV/AIDS in rural areas are alluded to.
      Finally, some of the limitations of the clinical nurse specialist role are
      delineated and some consideration is given to the future role of clinical nurse
      specialists for HIV and AIDS.

PMID- 9543054
TI  - Decision making: the context of nurse prescribing.
AB  - From October 1994 qualified district nurses and health visitors from eight
      demonstration sites in England have been able to prescribe from a limited list of
      formulary items. Data collected from nurses formed only one part of the
      evaluation of nurse prescribing. These data highlighted a number of areas where
      prescribing nurses were faced with difficult decisions. A number of authors have
      considered how both doctors and nurses make decisions, and the factors which may
      influence the decision making process. With reference to the literature this
      paper focuses on the findings related to decision making in the context of nurse
      prescribing.

PMID- 9543055
TI  - Clinical nurse specialisation: the route to future practice? Conference organised
      by Professional Nurse, held at the Kensington Town Hall, London, England, 24-25
      November 1997.

PMID- 9543056
TI  - T cell-depleted autologous hematopoietic stem cell transplantation for multiple
      sclerosis: report on the first three patients.
AB  - Multiple sclerosis (MS) is a disease of the central nervous system characterized
      by immune-mediated destruction of myelin. In patients with progressive
      deterioration, we have intensified immunosuppression to the point of
      myeloablation. Subsequently, a new hematopoietic and immune system is generated
      by infusion of CD34-positive hematopoietic stem cells (HSC). Three patients with
      clinical MS and a decline of their Kurtzke extended disability status scale
      (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS
      of 8.0 at the time of enrollment were treated with hematopoietic stem cell (HSC)
      transplantation using a myeloablative conditioning regimen of cyclophosphamide
      (120 mg/kg), methylprednisolone (4 g) and total body irradiation (1200 cGy).
      Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells. The
      average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of
      all immunosuppressive medications, functional improvements have occurred in all
      three patients. We conclude that T cell-depleted hematopoietic stem cell
      transplantation can be performed safely in patients with severe and debilitating
      multiple sclerosis. Stem cell transplantation has resulted in modest neurologic
      improvements for the first time since onset of progressive disease although no
      significant changes in EDSS or NRS scales are evident at this time.

PMID- 9543057
TI  - T cell-depleted bone marrow transplantation and delayed T cell add-back to
      control acute GVHD and conserve a graft-versus-leukemia effect.
AB  - Thirty-eight patients with hematological malignancies, received T cell-depleted
      marrow transplants (BMT) and cyclosporine to prevent acute graft-versus-host
      disease (aGVHD), followed by delayed add-back of donor lymphocytes to prevent
      leukemia relapse. In 26 patients scheduled for donor T cell add-back of 2 x 10(6)
      cells/kg on day 30 and 5 x 10(7) cells/kg on day 45 (schedule 1), the overall
      probability of grade > or = II aGVHD developing was 31.5%, with a 15.5%
      probability of aGVHD occurring after T cell add-back. In 12 patients receiving
      10(7) donor T cells/kg on day 30 (schedule 2), the probability of grade > or = II
      aGVHD was 100%. The incidence of grade III-IV aGVHD was higher in schedule 2 than
      in schedule 1 (P=0.02). Of 24 evaluable patients, 10 (46%) developed chronic GVHD
      which was limited in eight and extensive in two. Current disease-free survival
      for 18 patients at standard risk for relapse (chronic myeloid leukemia (CML) in
      chronic or accelerated phase, acute myeloid leukemia in remission) vs 20 patients
      with more advanced leukemia or multiple myeloma were respectively 72% vs 12% (P <
      0.01) with a 29% vs 69% probability of relapse (P=0.08). In 12 CML patients
      surviving more than 3 months, PCR analysis of the BCR/ABL transcript showed that
      minimal residual disease after T cell add-back was transient except in two
      patients who developed hematological relapse. Results indicate that the risk of
      acute GVHD is low following substantial T cell doses, transfused 45 days after
      transplant, using cyclosporine prophylaxis. Furthermore a graft-versus-leukemia
      effect was conserved.

PMID- 9543058
TI  - Generation of leukemia-reactive cytotoxic T lymphocytes from HLA-identical donors
      of patients with chronic myeloid leukemia using modifications of a limiting
      dilution assay.
AB  - Donor leukocyte transfusions (DLT) have an anti-leukemic effect in most patients
      with a relapse of chronic myeloid leukemia (CML) after allogeneic stem cell
      transplantation. However, DLT are often complicated by graft-versus-host disease.
      Selection of donor lymphocytes with a relative specificity for leukemic cells is
      desirable. The generation of leukemia-reactive cytotoxic T lymphocyte (CTL)
      responses between HLA-identical donors and patients in bulk cultures showed major
      variations, and false negative results were observed. In a modification of a
      limiting dilution analysis (LDA) two-fold serial dilutions of HLA-identical donor
      mononuclear cells (MNC) were cultured in the presence of CML cells. The anti
      leukemic CTL precursor frequencies in these donors varied between <1 and 9 per
      106 MNC. HLA-restricted CD4+ or CD8+ lymphocytes as well as MHC non-restricted
      gammadelta T cells were responsible for the anti-leukemic responses. A positive
      correlation between cytotoxicity in the various wells after 3, 4 and 5 weeks of
      culture could be found. The LDA may be superior to bulk cultures in selecting
      stable immune responses and in separating multiple different anti-leukemic T cell
      responses in each donor-patient combination.

PMID- 9543059
TI  - CD34+ cells mobilized by cyclophosphamide and granulocyte colony-stimulating
      factor (G-CSF) are functionally different from CD34+ cells mobilized by G-CSF.
AB  - Mobilized peripheral blood progenitor cells (PBPC) are increasingly used as an
      alternative to bone marrow for autografting procedures. Currently,
      cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF)
      or G-CSF alone are the most commonly used PBPC mobilization schedules. In an
      attempt to investigate whether the use of these two mobilization regimens could
      result in the collection of functionally different CD34+ cells, we analyzed
      nucleated cells (NC), CD34+ cells, committed progenitor cells and long-term
      culture initiating-cells (LTC-IC) in 52 leukaphereses from 26 patients with
      lymphoid malignancies, mobilized either by CY+G-CSF (n=16) or G-CSF alone (n=10).
      Thirty-four aphereses from the CY+G-CSF group and 18 aphereses from the G-CSF
      group were investigated. According to the study design, leukaphereses were
      carried out until an average number of 7 x 10(6) CD34+ cells/kg body weight were
      collected. The mean (+/-s.e.m.) numbers of CD34+ cells mobilized per apheresis by
      CY+G-CSF and G-CSF were not significantly different (2.76+/-0.6 x 10(8) vs 2.53+/
      0.4 x 10(8), P < or = 0.7). This resulted from a mean number of NC that was
      significantly lower in the CY+G-CSF products than in the G-CSF products (12.4+/
      1.7 x 10(9) vs 32+/-5.4 x 10(9), P < or = 0.0001) and a mean incidence of CD34+
      cells that was significantly higher in the CY+G-CSF products than in the G-CSF
      products (2.9+/-0.6% vs 0.9+/-0.2%, P < or = 0.0018). The mean (+/-s.e.m.) number
      of CFU-GM collected per apheresis was significantly higher in the CY+G-CSF group
      than in the G-CSF group (37+/-7 x 10(6) vs 14+/-2 x 10(6), P < or = 0.03).
      Interestingly, CY+G-CSF-mobilized CD34+ cells had a significantly higher plating
      efficiency than G-CSF-mobilized CD34+ cells (25.5+/-2.9% vs 10.8+/-1.9%, P < or =
      0.0006). In addition, the mean number of LTC-IC was significantly higher in the
      CY+G-CSF products than in the G-CSF products (6.3+/-1 x 10[6] vs 3.3+/-0.3 x
      10[6], P < or = 0.05). In conclusion, our data provide evidence that CY+G-CSF and
      G-CSF induce the mobilization of CD34+ cells with different clonogenic potential.
      As mobilized PBPC containing large numbers of progenitors lead to safer
      transplantation, this issue may have implications for planning mobilization
      strategies.

PMID- 9543060
TI  - Long-term results of autologous marrow transplantation for relapsed or refractory
      male or female germ cell tumors.
AB  - Twenty-one patients with relapsed or refractory germ cell tumors were treated
      with high-dose chemotherapy and marrow transplantation (HDC/BMT) from 1982-1993.
      Primary sites of disease were testis (17), ovary (three), and pineal gland (one).
      Pathology included dysgerminoma (one), choriocarcinoma with adenocarcinoma (one),
      seminoma (four), and nonseminoma or mixed germ cell tumor (15). Nineteen had at
      least two prior chemotherapy regimens and eight had cisplatin-refractory disease
      defined as progression within 4 weeks of a cycle of cisplatin-based chemotherapy.
      HDC regimens were mostly combinations of cyclophosphamide with etoposide and
      cisplatin or carboplatin. There were only two treatment-related deaths
      (aspergillosis and interstitial pneumonitis). Times to engraftment of
      granulocytes (21+/-8.3 days) and platelets (32+/-20.2 days) were reasonable with
      only the last nine patients receiving growth factors. At a minimum of 4 years
      follow-up, eight patients have died of disease, six of whom were cisplatin
      refractory prior to transplant. Eleven patients (52% overall) are alive and
      continuously free of disease after 4-10 years including one of three with
      refractory ovarian germ cell tumor. HDC/BMT provides significant long-term
      disease-free survival as salvage therapy for both male and female relapsed germ
      cell tumor patients who are not refractory to cisplatin.

PMID- 9543061
TI  - The role of thalidomide in the treatment of refractory chronic graft-versus-host
      disease following bone marrow transplantation in children.
AB  - Chronic graft-versus-host disease (cGVHD) is a frequent complication of
      allogeneic bone marrow transplantation (BMT). Thalidomide was found to have
      immunosuppressive properties and it has been used in a limited number of children
      with cGVHD. We report our experience with refractory and/or high-risk cGVHD in 14
      children. Six children showed complete clinical response to thalidomide in a
      median time of 2 months. Four children had partial responses and four failed.
      Side-effects were usually mild (somnolence, constipation) and only two patients
      developed sensory peripheral neuropathy. An increased incidence of infectious
      complications attributable to thalidomide was not observed. Nine out of 10
      responding patients are alive 49-111 months post-BMT. Thalidomide can be
      effective particularly in children with prevailing mucocutaneous cGVHD. All
      patients should be carefully monitored to detect peripheral neuropathy early.

PMID- 9543062
TI  - Relative importance of CD4+ and CD8+ T cell repertoires in the development of
      acute graft-versus-host disease in a murine model of bone marrow transplantation.
AB  - T cell repertoire alterations occurring after allogeneic BMT and related
      emergence of aGVHD has not been directly demonstrated. CD4, CD8 and Vbeta usage
      of T cells infiltrating spleen, lymph nodes and liver was compared in lethally
      irradiated F1(DBA/2 x B10.D2) recipients which develop (GVHD mice) or not (long
      survivor:LS mice) aGVHD across minor histocompatibility antigens (mHAgs) and Mtv
      6 and Mtv-7 encoded super-antigens (SAgs) barriers according to experimental
      conditions. The early expansion in GVHD mice of CD4Vbeta6+ and of CD4Vbeta3+ T
      cell subsets specific for Mtv-7 and Mtv-6 SAgs, respectively, is abolished in LS
      protected mice. By contrast, CD8+ T cells infiltrate lymph nodes, the liver but
      not the spleen of LS as in GVHD mice. Vbeta subset overexpression is frequent in
      all T cell phenotypes in GVHD but only among CD8+ T cells in LS mice. Predominant
      Vbeta pattern subpopulation is unique to each mouse. Overexpressed Vbeta
      subpopulation sequencing clearly indicates that expansion results from a very
      limited number of clones. Association of a given Vbeta segment with different
      Jbeta for each mouse suggests that the response is directed towards many
      different antigens. The data emphasize that Mtv-SAg and mHAgs CD4+ T cells are of
      crucial importance during GVHD and that there is no relationship between CD8+ T
      cell repertoires and pathological status.

PMID- 9543063
TI  - Streptococcus viridans bacteremia following autologous peripheral blood stem cell
      transplantation.
AB  - A retrospective evaluation of 200 consecutive recipients of autologous peripheral
      blood stem cell transplantation was conducted to ascertain the incidence and
      outcome of Streptococcus viridans bacteremia as well as to determine the role of
      prophylactic ampicillin therapy in the peri-transplant setting. Viridans
      streptococci were isolated from the blood of 35 individuals at a median of 6 days
      (range 2-8 days) following stem cell infusion. The most common isolates were S.
      sanguis and S. mitis. All patients received ciprofloxacin orally during the peri
      transplant period. Additionally, 79 patients received oral ampicillin
      prophylactically against gram-positive cocci. Although none of the patients
      suffered a fatal outcome, three individuals developed respiratory compromise
      requiring mechanical ventilation. Female sex proved to be the only independent
      risk factor for viridans streptococcal bacteremia (P=0.04). The shorter duration
      of neutropenia observed after stem cell transplantation did not impact on the
      incidence of S. viridans infections. Moreover, the prophylactic use of ampicillin
      failed to decrease the incidence of viridans sepsis and selected out organisms
      that were resistant to beta-lactam antibiotics.

PMID- 9543064
TI  - Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant
      patients: relationship between peak virus load, donor/recipient serostatus, acute
      GVHD and CMV disease.
AB  - Quantitative competitive PCR was used to monitor the quantity of cytomegalovirus
      (HCMV) in 1647 blood samples from 110 BMT recipients. DNAemia was detected in
      49/110 (45%) of the patients, of whom 15/49 experienced HCMV disease. Peak virus
      load during surveillance was elevated in symptomatic (median 4.5 log10
      genomes/ml) vs asymptomatic patients (median 3.6 log10 genomes/ml, P=0.002) and
      was also significantly elevated in HCMV seropositive recipients of seronegative
      marrow, (R+D-, median 5.0 log10), compared to those in the R-D- and R+D+ groups
      (P < 0.01 and <0.005). Odds ratios for disease per 0.25 log10 increase in viral
      load, recipient seropositivity and aGVHD were 1.43 (P=0.004), 6.60 (P=0.05) and
      3.17 (P=0.08), respectively. In multivariate logistic regression analysis only
      elevated viral load remained a significant risk factor for HCMV disease. The
      computed disease probability viral load curve showed a rapid increase in disease
      risk at viral loads between 3.8 and 5.5 log10 genomes/ml in blood, and odds
      ratios for disease were determined for different threshold viral loads. These
      data demonstrate the central role of viral load in the pathogenesis of HCMV in
      BMT recipients and provide an additional marker for targeting and monitoring
      therapy.

PMID- 9543065
TI  - Prospective economic evaluation accompanying a trial of GM-CSF/IL-3 in patients
      undergoing autologous bone marrow transplantation for Hodgkin's and non-Hodgkin's
      lymphoma. IL-3 BMT Study Team.
AB  - Our objective was to assess the economic impact of a new cytokine therapy that
      was being compared to standard therapy as supportive care in patients receiving
      autologous bone marrow transplantation for treatment of lymphoma. We performed an
      economic study accompanying a multicenter, randomized, controlled clinical trial
      in academic medical centers. One hundred and fifteen patients consented to
      participate in a parallel economic study of a randomized controlled trial of
      sequential IL-3 followed by GM-CSF vs GM-CSF alone after autologous bone marrow
      transplantation. We measured costs and quality-adjusted survival over a 13-month
      follow-up period. For the 13-month study period, the total cost estimates were
      $79892 (95% CI $69343 to $90544) for patients receiving GM-CSF alone and $89651
      (95% CI $79769 to $102114) for patients receiving IL-3/GM-CSF. The difference was
      not statistically significant. During the 13-month study period, the total number
      of quality-adjusted life-months in the GM-CSF arm was 6.67 (95% CI 5.75 to 7.56)
      months, while the total number of quality-adjusted life-months in the IL-3 arm
      was 6.26 (95% CI 5.34 to 7.15) months. The difference in quality-adjusted life
      months between the two treatment arms was not statistically significant. We
      conclude that economic analysis of a phase III clinical trial of IL-3/GM-CSF
      compared with GM-CSF alone showed no significant effect of IL-3 on the costs of
      care for patients undergoing bone marrow transplantation for a period of up to 13
      months after the procedure. This study demonstrates the feasibility of
      prospective economic evaluation within phase III trials of new cancer therapies.
      Data from this type of economic protocol could be used to help physicians,
      patients and managed care organizations understand the effect of new treatments
      from both a clinical and an economic perspective.

PMID- 9543066
TI  - Bone marrow infarction due to acute graft-versus-host disease in an acute
      lymphoblastic leukemia patient after unrelated bone marrow transplantation.
AB  - We report a case of bone marrow infarction in a 20-year-old woman with acute
      lymphocytic leukemia (ALL) who underwent unrelated bone marrow transplantation
      (BMT). Hematopoietic engraftment occurred on day 9 and, thereafter, the patient
      developed acute dermal and hepatic graft-versus-host disease (GVHD). She also
      experienced severe arthralgia in her knee joints on day 21. Immunosuppressive
      therapy with prednisolone (PSL) for acute GVHD was given, and the arthralgia
      improved rapidly, correlating with the improvement in dermal and hepatic GVHD.
      Based on the laboratory findings and analysis of magnetic resonance images, she
      was diagnosed as having bone marrow infarction. The cause of the bone marrow
      infarction was thought to be acute GVHD-related microangiopathy.

PMID- 9543067
TI  - Fatal CMV pneumonia associated with steroid therapy after autologous
      transplantation in patients previously treated with fludarabine.
AB  - Fludarabine has been associated with an increased risk of opportunistic
      infections, possibly related to the induction of profound CD4+ lymphopenia. We
      observed two cases of cytomegalovirus pneumonia (CMV-IP) in a total of nine
      patients over a 5-year period who had previously received fludarabine and who
      proceeded to autografting. Both patients also received steroids post-transplant.
      CMV-IP was observed in one of 104 other autograft recipients over this time who
      had not received prior fludarabine. This observation suggests that the
      combination of fludarabine pre-transplant and steroids post-transplant may
      increase the risk of invasive CMV disease in autograft recipients.

PMID- 9543068
TI  - B cell lymphoma-associated hemophagocytic syndrome after PBSCT.
AB  - Hemophagocytic syndrome (HPS) associated with T cell lymphoma is well known, but
      an association with B cell lymphoma is rare. We report a patient who developed
      subcutaneous non-Hodgkin's lymphoma (NHL) of B cell origin. Autologous peripheral
      blood stem cell transplantation (PBSCT) was undertaken in her second complete
      remission (CR), but HPS appeared 5 months after transplantation. The patient
      deteriorated rapidly and died of metabolic acidosis. Necropsy revealed that she
      had relapsed B cell NHL involving liver, spleen and bone marrow. B cell NHL after
      PBSCT, associated with HPS as an initial sign, is rare. We report this case and
      review the literature.

PMID- 9543069
TI  - Treatment of MPS VII (Sly disease) by allogeneic BMT in a female with homozygous
      A619V mutation.
AB  - A 12-year-old girl with Sly disease (mucopolysaccharidosis VII; beta
      glucuronidase deficiency), who is homozygous for the A619V mutation, had a
      successful allogeneic BMT, donored by an HLA-identical unrelated female to
      replace the deficient enzyme. Within 5 months after BMT, the enzyme activity of
      the recipient's lymphocytes increased to normal range. No signs of acute or
      chronic GVHD were observed. For the successive 31 months post-BMT, beta
      glucuronidase activity in her lymphocytes was maintained at almost normal levels
      and excretion of glycosaminoglycans in the urine was greatly diminished.
      Ultrastructural findings demonstrated no abnormal vacuoles and inclusion bodies
      in the cytoplasm of her rectal mucosal cells. Coincident with the restoration of
      the enzyme activity, clinical improvement was dramatic. Especially notable were
      improvements in motor function. The patient was able to walk alone for a long
      time without aid, and she even became able to ride a bicycle and take a bath. In
      addition, recurrent infections of the upper respiratory tract and the middle ears
      decreased in frequency and severity, and dyspnea on exertion, severe snoring and
      vertigo have substantially improved. Thus, allogeneic BMT in this patient
      produced a better quality of life and provided a more promising outlook.

PMID- 9543070
TI  - Toxoplasma retinitis/encephalitis 9 months after allogeneic bone marrow
      transplantation.
AB  - In a 34-year-old patient toxoplasma retinitis/encephalitis developed 9 months
      after bone marrow transplantation. The BMT was complicated with a serious GVHD.
      Although she initially responded well to antibiotic therapy she died 2 years
      after BMT due to progressive infection.

PMID- 9543071
TI  - Successful treatment of severe Shulman's syndrome by allogeneic bone marrow
      transplantation.
AB  - We describe a patient with severe Shulman's syndrome (ShS) (eosinophilic
      fasciitis). This auto-immune disease involved not only the skin and muscles, but
      the bone marrow as well - thereby fulfilling the criteria of severe aplastic
      anemia. As the disease was steroid-resistant, the patient underwent allogeneic
      bone marrow transplantation (BMT). Remission of ShS was achieved. Eight months
      later chronic GVHD developed and relapse of ShS (probably induced by GVHD)
      occurred. He was successfully treated with corticosteroids and the disappearance
      of GVHD was followed by cessation of the symptoms of ShS. At present (34 months
      following BMT) he is doing well and displays no signs of ShS or GVHD. This case
      suggests that an aggressive immunoablative preparative regimen with subsequent
      allogeneic BMT can result in long-lasting clinical remission of a severe auto
      immune disease.

PMID- 9543072
TI  - Beta2-adrenoceptor responsiveness and asthma activity.

PMID- 9543073
TI  - Can asthma be prevented? Evidence from epidemiological studies of children in
      Australia and New Zealand in the last decade.

PMID- 9543074
TI  - Symptom control in patients with hay fever in UK general practice: how well are
      we doing and is there a need for allergen immunotherapy?
AB  - BACKGROUND: Seasonal allergic rhinitis is often regarded as a trivial condition
      which patients should treat themselves. However, a significant proportion of
      sufferers are not fully controlled on standard hay fever medication, either
      because they do not use it properly or because their symptoms are resistant to
      standard therapy. The latter group may be suitable for allergen immunotherapy,
      which was once widely available in UK general practice but is now only available
      through specialist centres. AIMS: To describe the symptom control of patients
      with hay fever, to assess concordance with prescribed medication, and to estimate
      the number of patients who may benefit from referral for allergen immunotherapy.
      SETTING: General practices in Hampshire and Dorset, UK. METHOD: Survey of adult
      hay fever sufferers prescribed a non-sedating antihistamine and nasal steroid
      spray by their general practitioner. A postal questionnaire was sent to all
      eligible patients aged 16-64 registered with 16 general practices. Self
      assessment of symptom control and reported compliance with medication were used
      to identify those patients who were suboptimally controlled and might therefore
      benefit from immunotherapy. RESULTS: Eight hundred and forty-six out of 62500
      registered patients aged 16-64 (1.4%) were receiving both drugs, and responses
      were received from 627 (74.1%); 526 of these met the full entry criteria. One
      hundred and forty-two patients (27.0%) were using both types of drug regularly.
      Of the 142 patients using optimum pharmacotherapy, 54 (38.0%) reported good
      control of their hay fever symptoms. The remaining 62.0% experienced troublesome
      residual symptoms and described symptom control as partial or poor. Among those
      using suboptimal pharmacotherapy, 181/376 (48.1%) reported good control.
      CONCLUSION: Many patients are using treatment inappropriately. Current guidelines
      need to be applied better but there is also a significant burden of residual
      symptoms, even among those receiving current optimal therapy. This indicates a
      need for patients with severe summer hay fever to receive specialist assessment.

PMID- 9543075
TI  - Seasonal variations in cyclic AMP production by peripheral blood mononuclear
      cells in allergic asthmatics.
AB  - BACKGROUND: Dysfunction of the beta-adrenoceptor (betaAR)/adenylyl cyclase (AC)
      system can impair the response of different cell types, including lymphocytes. In
      asthma, impairment of this system as well as changes in cytokine production by
      lymphocytes have been described. Because the severity of asthma can change over
      the year, a circannual pattern of the betaAR/AC system activity may also exist.
      OBJECTIVES: We set out to examine the activity of this betaAR/AC signal
      transduction system in peripheral blood mononuclear cells (PBMCs) of allergic
      asthmatics to asses whether differences existed between seasons. We investigated
      whether changes were associated with asthma severity and circannual changes in
      serum cortisol levels. METHODS: During 19 months, 41 allergic asthmatics (mean
      age 28 years) with nocturnal airway obstruction were enrolled in the study. AC
      activity was measured by cyclic AMP production. Resting, stimulated and
      potentiated AC activities and their relationships with clinical parameters,
      seasonal influences and serum cortisol levels were assessed. RESULTS: The AC
      activity in resting, stimulated and potentiated cells varied during the year. AC
      activity was relatively low in the periods June-August and September-November,
      and higher in December-February and March-May. Receptor-mediated and potentiated
      responses expressed as percentage of the resting response were equivalent
      throughout the year. Serum cortisol levels were positively related to AC
      activity. No relationships were found between clinical parameters and AC activity
      or serum cortisol levels. CONCLUSIONS: These results indicate that AC activity in
      PBMCs of allergic asthmatics shows a seasonal variation. However, seasonal
      differences in AC activity seems to be unrelated with clinical parameters. Other
      factors such as serum cortisol levels may have a modulating influence on AC
      activity. Future studies of AC systems in blood cells of asthmatic patients need
      to take into account these seasonal influences.

PMID- 9543076
TI  - Expression of cyclo-oxygenase 1 and 2 proteins in upper respiratory mucosa.
AB  - BACKGROUND: Cyclo-oxygenases 1 (Cox-1) and 2 (Cox-2) catalyse the conversion of
      arachidonic acid to prostaglandin endoperoxides, leading to the formation of
      prostaglandin and thromboxane mediators of inflammation. The involvement of these
      enzymes in inflammatory disorders such as sinusitis and nasal polyps is unknown
      although this may be relevant to their pathophysiology. METHODS: We studied Cox-1
      and Cox-2 immunoreactivities in nasal polyp, maxillary sinus, and turbinate
      biopsies obtained from eight patients with chronic allergic rhinitis and
      sinusitis and/or nasal polyps, 15 patients with chronic non-allergic rhinitis and
      sinusitis and/or nasal polyps and five control subjects (patients requiring nose
      surgery not related to sinusitis or nasal polyps). RESULTS: Both Cox- and Cox-2
      were mainly expressed in the epithelium (basal, ciliated) and were found in 16/28
      and 25/28 subjects for Cox-1 and Cox-2 respectively. We did not find any
      differences between the patient populations. There were no correlations between
      any of the clinical parameters studied nor the pathological patterns and the
      presence and characteristics of the Cox immunoreactivities. CONCLUSION: Both
      cyclo-oxygenase enzymes are expressed in normal human upper respiratory
      epithelium and are not upregulated in chronic sinusitis nor in nasal polyposis,
      possibly suggesting that Cox products do not have an important role as mediators
      of the chronic upper airway inflammation.

PMID- 9543077
TI  - Changes in sputum composition during sputum induction in healthy and asthmatic
      subjects.
AB  - BACKGROUND: Induced sputum is increasingly used to characterize the cellular and
      biochemical composition of the airways. OBJECTIVE: We studied whether the
      composition of induced sputum is different between samples obtained sequentially
      during one sputum induction. METHODS: Subjects with mild asthma (n=7) or healthy
      subjects (n=6) produced sputum during and after three consecutive 10 min periods
      of hypertonic saline inhalation. Samples were analysed separately for the three
      periods. To determine the reproducibility of the cellular composition, sputum
      induction was repeated on another two days. RESULTS: The mean percentage of
      neutrophils decreased significantly (P<0.01) during sputum induction in asthmatic
      (36.9, 29.8, 16.3%) and healthy subjects (43.6, 17.2, 18.0%). Correspondingly,
      percentages of macrophages increased and percentages of eosinophils were 4.9,
      3.5, and 3.7% in the asthmatic and 0.6, 0.7, and 0.5% in the healthy subjects,
      without significant change over the three periods; mean eosinophil numbers were
      significantly higher in the subjects with asthma (P< 0.05). Reproducibility of
      percentage cell counts did not markedly depend on sampling periods in terms of
      coefficients of variation. The concentration of eosinophil cationic protein
      decreased in both groups during sputum induction (P<0.01), geometric mean values
      being 579, 143, 57.4 microg L(-1) in the asthmatic and 130, 47.3, 28.4 microg L(
      1) in the healthy subjects. Similar changes were seen for lactate dehydrogenase.
      CONCLUSION: The separate analysis of induced sputum from three consecutive
      sampling periods of a single induction procedure demonstrated significant changes
      in their cellular and biochemical composition, both in healthy and mild asthmatic
      subjects.

PMID- 9543078
TI  - Intranasal fluticasone propionate reduces ICAM-1 on nasal epithelial cells both
      during early and late phase after allergen challenge.
AB  - BACKGROUND: Allergen specific nasal challenge (ASNC) is an optimal method to
      study the pathophysiological mechanisms sustaining the allergic inflammation and
      in particular the adhesion molecule system, which is involved in cellular
      infiltration of nasal mucosa. Topical steroids have been accepted as a highly
      effective anti-inflammatory therapy for allergic rhinitis. OBJECTIVE: The aim of
      this double-blind placebo- controlled study was the evaluation of clinical and
      cytological parameters, including ICAM-1 expression on nasal epithelial cells,
      after a 4 week treatment with nasal fluticasone propionate (200 microg/daily) or
      placebo, using the model of ASNC. METHODS: Twenty allergic rhinitics underwent
      nasal challenge before and after treatment. The following parameters were
      evaluated: (i) nasal symptoms (rhinorrhoea, itching, sneezing, obstruction), (ii)
      inflammatory cells (eosinophils and neutrophils), (iii) ICAM-1 expression on
      nasal epithelial cells at baseline, 30 min (early phase) and 6 h (late phase)
      after ASNC. RESULTS: Fluticasone propionate was capable of reducing: (i) clinical
      symptoms during both early (P<0.001) and late phase (P<0.04), (ii) eosinophil
      (P<0.002) and neutrophil (P<0.001) infiltrate during late phase, and (iii) ICAM-1
      expression on nasal epithelial cells during both early (P < 0.01) and late phase
      (P < 0.03). CONCLUSIONS: The present results demonstrate that fluticasone
      propionate exerts a significant action on early and late phase clinical events
      following specific nasal challenge, reducing also the cellular influx during the
      late phase. This event is likely due to the modulation of ICAM-1 expression on
      epithelial cells.

PMID- 9543079
TI  - Determinants of eosinophil cationic protein in nasal lavages in children.
AB  - BACKGROUND: Nasal lavages are increasingly used to assess airways inflammation in
      children. However, there are no studies assessing how measurement error as well
      as biological influences contribute to the concentration of nasal inflammatory
      parameters in a population based survey. OBJECTIVE: To investigate determinants
      of concentration of eosinophil cationic protein (ECP) in nasal lavages we studied
      147 schoolchildren (mean age 8.1 years, SD 0.6 years) by repeated nasal
      lavages/year over a 2 year period. METHODS: Standardized questionnaires were
      completed by the parents each year. A skin-prick test with seven aeroallergens
      (birch, cat, dog, hazel, weeds, Dermatophagoides pteronyssinus and D. farinae)
      was performed. One hundred and one children could perform valid lavages at least
      five times a year. As a measure of reproducibility the intraclass coefficient of
      reliability was calculated. RESULTS: The intraclass coefficient of reliability
      was 0.27 over all observations suggesting that about a quarter of total variance
      is due to between-subject variance. Taking means over each year increased
      reliability to 0.60. Linear regression analyses with ECP being the dependent
      variable demonstrated significant higher values for boys (beta=12.26; P < 0.01),
      children sensitized to seasonal (beta=34.27; P=0.02) but not to perennial
      allergens (beta=-4.44; P=0.57), and for children with a serous (beta=10.01;
      P=0.01) or purulent rhinitis (beta=22.45; P < 0.001). CONCLUSION: Assessment of
      inflammatory mediators in nasal lavages is a useful tool for epidemiological
      paediatric studies. However, due to the relatively high intraindividual
      variability of ECP concentrations multiple lavages are necessary to characterize
      the individual.

PMID- 9543080
TI  - Changes in CD23 expression of blood and skin in atopic eczema after Chinese
      herbal therapy.
AB  - BACKGROUND: Aberrant expression of CD23 (low affinity IgE receptor) on cells of
      the monocyte/macrophage series in peripheral blood and lesional skin of patients
      with atopic eczema has been demonstrated. It is not known whether this
      abnormality results from a fundamental systemic problem of the monocytes of these
      patients or reflects local changes to cell populations within the skin tissues.
      OBJECTIVES: This study was designed to determine whether this aberrant expression
      was caused by local cutaneous influences on mature cells or fundamental changes
      in monocyte differentiation. The possible relationship between these aberrations
      and clinical severity was also investigated by repeating these immunopathological
      studies after a course of efficacious treatment with Chinese herbal therapy
      (CHT). METHODS: Peripheral blood mononuclear cells were obtained from patients
      with atopic eczema before, and after 8 weeks of treatment. Efficacy of CHT was
      quantified on clinical grounds. Monocytes were isolated by adherence to plastic
      and cultured for up to 7 days. Samples were harvested at 2, 5 and 7 days of
      culture and cytospins prepared. Immunocytochemical staining to identify
      phenotypic subsets was performed on the monocytes at time 0 and on maturing cells
      from culture. This immunocytology was quantified using computerized image
      analysis equipment to determine the emergence of macrophage subsets and their
      level of CD23 expression. Biopsies were taken from lesional skin before and after
      treatment and immunohistology was performed on cryostat sections to determine the
      number of antigen presenting cells expressing CD23 as well as the level of
      expression of these molecules. RESULTS: The results showed that increased numbers
      of monocytes from patients with atopic eczema express CD23 at day 0 and that
      cultured monocytes from these patients differentiate faster during the 7 day
      culture period as compared to normal controls. Efficacious treatment did not
      affect the number of peripheral blood monocytes expressing CD23. However,
      treatment did lead to a significant decrease in the number of CD23+ mature
      macrophages in the skin as well as a reduction in the level of expression of this
      moiety. These results demonstrate that changes in clinical severity are more
      closely related to the expression of CD23 on mature antigen presenting cells in
      lesional skin rather than to differentiating peripheral blood monocyte CD23
      expression. CONCLUSIONS: These results suggests that local factors within
      lesional skin govern the accumulation and the expression of CD23 on mature
      macrophages and that these factors may be more relevant to the pathogenesis of
      the disease than aberrations in CD23 expression that may occur systemically.

PMID- 9543081
TI  - Post-translational modifications influence IgE reactivity to the major allergen
      Phl p 1 of timothy grass pollen.
AB  - BACKGROUND: Grass group I consists of very potent allergenic components which are
      found in the pollen of all temperate grasses. Several post-translational
      modifications are predicted from the cDNA data. OBJECTIVE: The aim of this study
      was to identify sequential IgE-binding sites on the allergen Phl p 1 and to
      determine their influence on IgE reactivity. METHODS: Based on cDNA data and
      microsequencing results we synthesized overlapping decapeptides covering the
      complete Phl p 1 molecule and tested them for immunological reactivity by means
      of the PEPSCAN technique. In a dot test we determined the frequency of IgE
      reactivities to post-translationally modified structures (hydroxylated proline
      residues, carbohydrate structure, and disulphide formations). RESULTS: Screening
      by overlapping peptides demonstrated an IgE binding site on the 10 N-terminal
      amino acids. Comprehensive studies showed that the two hydroxyproline residues of
      the native Phl p 1 allergen (at positions 5 and 8) and the N-glycan (at position
      9) can result in an increased IgE reactivity; 3.3% of the sera exclusively bound
      to the hydroxyproline bearing peptide, while only 0.4% bound to the proline
      containing peptide. With regard to glycosylation, we estimated that 20% of sera
      recognized protein and carbohydrate epitopes, while one serum exclusively bound
      to the glycan. The formation of disulphide bonds has no detectable effect on the
      IgE reactivity to Phl p 1. CONCLUSION: Our results indicate that the post
      translational modifications, the carbohydrate structure and the hydroxylation of
      proline residues, can enhance the IgE reactivity of Phl p 1.

PMID- 9543082
TI  - Limited genetic control of specific IgE responses to rye grass pollen allergens
      in Australian twins.
AB  - BACKGROUND: Both genetic and environmental factors are thought to contribute to
      specific IgE responses, however, the relative contribution of each in the
      responses to individual ryegrass pollen allergens is largely unknown even though
      some responses to allergens have been linked to certain HLA complexes. OBJECTIVE:
      Using a large group of monozygotic and dizygotic twins, this study was designed
      to investigate the IgE binding profiles of individual ryegrass pollen (Lolium
      perenne) components to assess the relative contribution of genetic and
      environmental factors in determining IgE responses to specific allergens.
      METHODS: Ryegrass pollen proteins were separated by electrophoresis and
      immunoblotted with sera from 191 pairs of twins where at least one sibling had a
      SPT > 2 mm to perennial ryegrass. Concordance levels for individual ryegrass
      pollen components were compared between monozygotic and dizygotic twins in a
      subset group where both twins had SPT > 3 mm to perennial ryegrass. RESULTS:
      Immunoblotting revealed 23 individual IgE-binding components from ryegrass
      pollen. Although there was a significantly greater proportion of monozygotic
      twins with SPT wheals greater than 3 mm when compared with the dizygotic twins,
      the mean case-wise concordance for the immunoblot components was similar for both
      groups of twins. The mean case-wise concordance when at least four pairs of sera
      were involved was 44% for the MZ twins (n=11 components) and 45% for the DZ twins
      (n=12 components). We found no significant differences in concordance levels for
      any of the 23 individual components including allergens previously associated
      with HLA. CONCLUSION: Evidence for genetic control of allergen-specific IgE
      responses in a large population sample of twins to individual ryegrass allergens
      is limited, indicating that the IgE responses to specific ryegrass pollen
      allergens are determined largely by environmental factors.

PMID- 9543083
TI  - Identification of volatile organic compounds emitted in the field by oilseed rape
      (Brassica napus ssp. oleifera) over the growing season.
AB  - BACKGROUND: Oilseed rape has been associated by rural dwellers with seasonal
      symptoms, such as sneezing, coughing, headache and eye irritation, during its
      flowering season, for a number of years. This study was performed to identify the
      volatile chemicals emitted from oilseed rape in the field. OBJECTIVE: The
      objective of this study was to establish which volatile chemicals may be
      causative factors of oilseed rape allergy/toxicity. METHODS: The volatile organic
      compounds were sampled over the flowering period using a modified entrainment
      technique for headspace analysis under field conditions. These volatiles were
      then identified using thermal desorption-gas chromatography-mass spectrometry.
      RESULTS: The major constituents identified were the monoterpenes limonene,
      sabinene, beta-myrcene, and cis-3-hexen-l-ol acetate, a 'green leaf' volatile.
      The minor constituents included monoterpenes, sesquiterpenes, short chain
      aldehydes and ketones, other 'green leaf' volatiles and organic sulphides
      including the respiratory irritant, dimethyl disulphide. CONCLUSIONS: This report
      highlights the diversity of volatile chemicals emitted by oilseed rape and
      confirms field emissions to be broadly similar to those found previously in
      laboratory studies. A review is carried out on the scientific literature already
      published on oilseed rape flower headspace analysis.

PMID- 9543085
TI  - IgG subclass responses to pigeon intestinal mucin are related to development of
      pigeon fanciers' lung.
AB  - BACKGROUND: Pigeon fanciers' lung (PFL) is a form of extrinsic allergic
      alveolitis. Affected individuals produce antibodies to various pigeon antigens,
      and the resulting immune complexes are thought to initiate the disease. However,
      high antibody titres also occur in some asymptomatic individuals. Previously
      attention has focused on protein antigens, but we have recently identified pigeon
      intestinal mucin as a novel antigen in PFL. OBJECTIVE: To determine the
      relationship between IgG subclass antibodies to pigeon intestinal mucin and the
      development of pigeon fanciers' lung. METHODS: Sera were collected from 250
      pigeon fanciers, who also completed a clinical questionnaire. Sera were screened
      for precipitating antibodies to pigeon serum and droppings. Individuals with
      symptoms and precipitating antibodies were considered to have classical PFL.
      Serum IgG and IgG subclass antibodies to pigeon intestinal mucin and pigeon serum
      proteins were investigated by quantitative enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Very high titres of IgG antibodies against pigeon mucin were
      found in all precipitin-positive individuals. A strong positive correlation was
      seen between titres of antibodies to mucin and to serum proteins, but this was
      not due to crossreactivity. No significant differences in IgG titres to either
      mucin or pigeon serum proteins were found between individuals with PFL and
      asymptomatic precipitin positive fanciers. IgG1 and IgG2 were the major
      subclasses of anti-mucin, with lower titres of IgG3. Patients with PFL had
      significantly higher titres of IgG1 to mucin than asymptomatic, precipitin
      positive individuals. In contrast, no significant differences were seen between
      PFL and asymptomatic precipitin-positive sera with respect to the subclass titres
      against pigeon serum proteins. CONCLUSION: The high titres of anti-mucin IgG in
      sera of all individuals with PFL, together with the finding that high IgG1 titres
      to mucin are associated with the development of disease confirm pigeon intestinal
      mucin as an important antigen in PFL.

PMID- 9543084
TI  - Analysis of T-cell reactive regions and HLA-DR4 binding motifs on the latex
      allergen Hev b 1 (rubber elongation factor).
AB  - BACKGROUND: The rubber elongation factor in Hevea rubber (Hev b 1) is one of the
      important latex-allergenic proteins inducing the production of specific IgE
      antibodies in latex-exposed subjects. In addition, Hev b 1 induces lymphocyte
      proliferation responses. A study about detailed T-cell epitope analysis of major
      latex allergens has not been published yet. OBJECTIVE: The aim of this study was
      to define the T-cell reactive regions on the latex allergen Hev b 1. METHODS:
      Nine overlapping peptides with 19 or 17 amino acid lengths representing the
      complete sequence of Hev b 1 were used for T-cell epitope mapping. Peripheral
      blood mononuclear cells (PBMCs) of latex-sensitized patients and healthy subjects
      were isolated and stimulated with the synthetic peptides to determine the
      specific proliferation response. The examined patients were sensitized to latex
      by occupational exposure (n=14) and suffered from rhinitis, conjunctivitis,
      contact urticaria and/or asthma. Two control groups of non-sensitized subjects
      were studied, one occupationally exposed to latex (n=4), the other one not
      exposed to latex (n=4). RESULTS: Positive proliferation response induced by one
      or more peptides was detected in 10 of the latex-sensitized patients and in two
      of the latex-exposed non-sensitized subjects. Each patient exhibited an
      individual epitope reactivity pattern. The whole protein was found to be
      immunogenic, but the intensity of lymphocyte responses induced by the peptides
      was different. The majority of the patients' PBMCs (more than 66%) responded to
      the peptides 31-49 and 91-109. Using the peptide selection of Stille's
      algorithms, three epitopes were predicted covering region 38-74 and two others
      covering region 82-104; the two peptides 31-49 and 91-109 are part of these
      regions. A strong HLA-DR4Dw4 (DRB1*0401)-binding motif according to published
      DR4w4 binding motifs was predicted in the region of 102-110 including peptide 91
      109 to which the majority of tested HLA-DR4-positive patients responded.
      CONCLUSIONS: Our data indicate that the whole 14 kDa protein Hev b 1 is
      immunogenic having regions that demonstrate individual and varying PBMC
      stimulation. Experimental data of T-cell reactive regions based on PBMC
      stimulation complement the information on T-cell epitope prediction. In addition,
      the Hev b 1 molecule contains a HLA-DR4Dw4 (DRB1*0401)-binding motif.

PMID- 9543086
TI  - Diethanolamine-induced occupational asthma, a case report.
AB  - BACKGROUND: Amino alcohols are low molecular weight chemicals used widely in
      industrial processes, often as minor constituents. They have been found to cause
      allergic contact dermatitis. Marked exposure through airways is uncommon in other
      than occupational settings where chemicals containing amino alcohols may be
      heated or vaporized, liberating free amino alcohols into the ambient air. A few
      cases of asthma and allergic rhinitis have been reported, but the amounts
      inducing the airway reactions have not been defined. OBJECTIVE: To further
      characterize ethanolamine-induced asthma and define the concentration inducing
      the asthmatic reaction, a case of diethanolamine-induced occupational asthma in a
      patient handling diethanolamine containing cutting fluid is reported. METHODS:
      Suspicion of work related asthma was raised by symptoms and peak expiratory flow
      monitorings at work and at home. Specific bronchial provocation tests with the
      cutting fluid containing DEA and with DEA aerosol at two different concentration
      below the American Conference of Governmental Industrial Hygienists threshold
      limit value of DEA (2.0 mg/m3) were done. RESULTS: DEA caused asthmatic airway
      obstruction at two different concentrations below the ACGIH TLV. A slight dose
      response relationship was observed. Specific IgE-antibodies against DEA could not
      be found. CONCLUSIONS: DEA is able to induce occupational asthma by a
      sensitization mechanism, the exact pathophysiological mechanism of which is not
      known.

PMID- 9543087
TI  - Occupational asthma in fruit salad processing.
AB  - BACKGROUND: Three subjects employed in the preparation of fruit for fruit salads
      reported work-related respiratory symptoms. Their work entailed removing the peel
      from citrus fruits, primarily oranges, following soaking of the fruits in a bath
      of enzymes including fungal derived pectinase and glucanase. Objectives To
      investigate the respiratory symptoms reported by these workers and determine
      their causes. METHODS: The three workers were investigated by a respiratory
      physician, including spirometry and serial peak flow measurements. Blood was
      taken for the measurement of IgE and IgG antibody responses against the enzyme
      solution. RESULTS: Predominant symptoms in these workers were shortness of
      breath, chest tightness and wheezing which were all alleviated at weekends and
      holidays only to occur when returning to work. Serial peak flow measurements
      showed a clear work-related pattern. All three had strong IgE responses to the
      enzyme solution used at the workplace and showed distinct patterns of binding in
      immunoblots. All three improved immensely following withdrawal from the workplace
      environment. CONCLUSION: Enzymes appear to be widely used in the preparation of
      fruit and although they are used in liquid form, exposure can occur to induce
      immunological sensitization and asthma.

PMID- 9543088
TI  - Oral sensitization to food proteins: a Brown Norway rat model.
AB  - BACKGROUND: Although several in vivo antigenicity assays using parenteral
      immunization are operational, no adequate enteral sensitization models are
      available to study food allergy and allergenicity of food proteins. OBJECTIVE:
      This paper describes the development of an enteral model for food allergy
      research in the Brown Norway (BN) rat. METHODS: The animals were exposed to
      ovalbumin either ad libitum via the drinking water (0.002 to 20 mg/mL)
      continuously for 6 weeks or by gavage (1 mg/mL per rat). Gavage dosing was
      performed either daily, twice a week, once a week or once every 2 weeks during a
      period of 6 weeks. No adjuvants were used during the sensitization studies.
      RESULTS: After intra-gastric administration of ovalbumin once or twice a week or
      once every two weeks, no or only a very low frequency of ovalbumin-specific
      antibody responses were detected. Daily intra-gastric dosing with ovalbumin
      resulted in antigen-specific IgG as well as IgE responses in almost all animals
      tested. Upon ad libitum exposure, ovalbumin-specific IgG but no ovalbumin
      specific IgE was detected. The cellular response was examined by determination of
      delayed-type hypersensitivity (DTH) reactions in the animals dosed by daily
      gavage and in the ad libitum exposed rats. Both sensitization protocols
      sensitized for DTH. The response was most pronounced in ad libitum exposed rats
      at day 28 of exposure. CONCLUSIONS: These studies show that the BN rat may
      provide a suitable animal model for inducing specific IgG and IgE responses as
      well as specific T-cell mediated hypersensitivity (DTH) to ovalbumin upon
      exposure via the enteral route without the use of adjuvants.

PMID- 9543089
TI  - Leflunomide, a novel immunomodulating agent, prevents the development of allergic
      sensitization in an animal model of allergic asthma.
AB  - BACKGROUND: Leflunomide is a new anti-inflammatory and immunomodulating agent
      which is showing promise in several immune disorders, especially rheumatoid
      arthritis. Its activity profile suggests it may be of use in modulating allergic
      sensitization. OBJECTIVE: To investigate the effectiveness of leflunomide in
      preventing the development of allergic sensitization. METHODS: Fifty-three brown
      Norway rats were sensitized by intraperitoneal injection of ovalbumin and
      adjuvant (ricin) on day 0. To determine the ability of leflunomide to inhibit
      primary allergic sensitization six rats were treated with A77 1726, the active
      metabolite of leflunomide, from day 0 through day 5, six were treated from day 5
      through day 10, and nine rats acted as controls. On day 14, ovalbumin-specific
      serum antibody levels and the magnitude of the early-phase airway response (EAR)
      after inhalation allergen challenge were assessed. To determine the ability of
      acute topical treatment with leflunomide to inhibit mast cell degranulation,
      three groups of five animals received either vehicle, 100 microg A77 1726, or
      1000 g A77 1726 60 min prior to aerosol allergen challenge. To determine the
      effects of leflunomide treatment in vivo on mast cell function in vitro, mast
      cells were obtained by bronchoalveolar lavage from 17 rats (nine treated with
      leflunomide and eight controls). Allergen-specific and non-specific degranulation
      (48/80 induced) were studied. RESULTS: In the leflunomide treated rats both
      ovalbumin-specific IgE and IgG levels were significantly reduced, and the
      increases in lung resistance and lung elastance were essentially abolished,
      compared to those of the control group. Non significant differences were found in
      any of the parameters between the two leflunomide treated groups. Topical pre
      treatment with leflunomide did not prevent the allergen-induced EAR. Treatment
      with leflunomide in vivo prevented allergen-induced mast cell degranulation in
      vitro because the mast cells lacked IgE on their surface. Non allergen-specific
      degranulation was normal and allergen-induced degranulation could be restored by
      passive sensitization. CONCLUSIONS: These data suggests that leflunomide can
      prevent primary allergic sensitization and prevent allergen-induced EAR by
      inhibiting production of allergen-specific IgE antibodies. Further studies in
      atopic conditions are warranted.

PMID- 9543090
TI  - A specific 15-lipoxygenase inhibitor limits the progression and monocyte
      macrophage enrichment of hypercholesterolemia-induced atherosclerosis in the
      rabbit.
AB  - Oxidant signalling and lipoprotein oxidation may play important roles in
      atherosclerotic lesion development. Given coincident localization of 15
      lipoxygenase (15-LO), stereospecific products of 15-LO and epitopes of modified
      LDL in atherosclerotic lesions, we hypothesized that inhibition of 15-LO by
      PD146176, an inhibitor of 15-LO with an IC50 in cells or isolated enzyme of 0.5
      0.8 microM, may limit atherosclerotic lesion development through regulation of
      monocyte-macrophage enrichment. Rabbits exposed to chronic endothelial denudation
      of the iliac-femoral artery were meal-fed a 0.25% cholesterol (C), 3% peanut oil
      (PNO), 3% coconut oil (CNO) diet twice daily with and without 175 mg/kg PD146176
      for 12 weeks. In a second study, atherosclerotic lesions were pre-established in
      rabbits through chronic endothelial denudation and meal-fed a 0.5% C, 3% PNO, 3%
      CNO diet for 9 weeks and a 0% C/fat diet for 6 weeks prior to an 8 week
      administration of PD146176 at 175 mg/kg, q.d. Plasma total and lipoprotein
      cholesterol exposure were similar in control and PD146176-treated animals in both
      studies but PD146176 increased plasma triglyceride exposure 2- to 4-fold. Plasma
      PD146176 concentrations ranged from 99 to 214 ng/ml at 2 h post-dose. In the
      progression study, the iliac-femoral monocyte-macrophage area was reduced 71%,
      cross-sectional lesion area was unchanged and cholesteryl ester (CE) content was
      reduced 63%. In the regression study, size and macrophage content of iliac
      femoral, fibrous plaque-like lesions were decreased 34%, CE content was reduced
      19% and gross extent of thoracic aortic lesions were reduced 41%. We conclude
      that PD146176 can limit monocyte macrophage enrichment of atherosclerotic lesions
      and can attenuate development of fibrofoamy and fibrous plaque lesions in the
      absence of changes in plasma total or lipoprotein cholesterol concentrations.

PMID- 9543091
TI  - The codon 55 polymorphism in the paraoxonase 1 gene is not associated with the
      risk of coronary heart disease in Asian Indians and Chinese.
AB  - Recently several but not all studies have implicated the codon 192 polymorphism
      in the paraoxonase 1 (PON1) gene with the risk of coronary heart disease (CHD).
      These findings suggest that this polymorphism is not functional but rather may be
      in linkage disequilibrium with a functional mutation in the PON1 or a nearby
      gene. In this investigation, we have evaluated the role of another common
      polymorphism in the PON1 gene at codon 55 with the risk of CHD in a biracial
      sample of Asian Indians and Chinese. We observed a significant inter-racial
      variability in the allelic distribution as the frequency of the less common
      allele, codon 55/L, was significantly higher in Indians than Chinese (0.202
      versus 0.036; P < 0.0001). However, despite this inter-racial difference the
      codon 55 polymorphism was neither associated with CHD risk nor with plasma
      lipoprotein-lipids variation in both racial groups. We also used two site
      haplotype data (codons 55 and 192) to assess the combined contribution of the two
      polymorphisms to the risk of CHD. There was a strong linkage disequilibrium
      between the two polymorphic sites in both racial groups (P < 0.0001). While the
      haplotype data revealed no association with CHD in Chinese, the frequency of the
      BL haplotype was significantly higher (0.430 versus 0.311; P = 0.004) and the
      frequency of the AL haplotype was significantly lower (0.368 versus 0.483; P =
      0.006) in Indian patients than controls. Since the B allele of the codon 192
      polymorphism was shown to be an independent risk factor for CHD in Indians in our
      previous study, the positive association of the BL haplotype with CHD appears to
      be mediated by the B allele with no independent contribution from the codon 55
      polymorphism.

PMID- 9543092
TI  - Remnant-like particle cholesterol is a major risk factor for myocardial
      infarction in vasospastic angina with nearly normal coronary artery.
AB  - We investigated the association of remnant-like particle cholesterol (RLP-C),
      with vasospastic angina (VSA). We selected 66 subjects with nearly normal
      coronary artery as a control group, and 74 VSA with nearly normal coronary
      artery, of whom 19 had prior myocardial infarction (MI). Coronary risk factors,
      triglyceride, lipoproteins and apolipoproteins were evaluated using stepwise
      discriminant analysis, smoking was the only discriminator of the control group
      from VSA and RLP-C was the only discriminator of VSA with MI from VSA without MI.
      In comparison between VSA with and without MI, using stepwise logistic regression
      analysis, the only significant variable was RLP-C, and odds ratio of RLP-C for MI
      was 1.59. Thus, RLP-C is a major discriminator of VSA with MI and appears to be a
      major risk factor for MI in VSA.

PMID- 9543093
TI  - R451Q mutation in the cholesteryl ester transfer protein (CETP) gene is
      associated with high plasma CETP activity.
AB  - Cholesteryl ester transfer protein (CETP), as a candidate gene for
      dyslipoproteinemia and coronary heart disease, was studied in 105 men with low
      plasma concentrations of high density lipoprotein cholesterol (HDL-C) and
      established coronary heart disease as well as in 515 randomly selected men and
      women. A one-nucleotide substitution (G to A) in exon 15, which changes arginine
      (451) to glutamine in CETP protein, was detected by PCR-SSCP and direct
      sequencing and screened in the population sample by a simple PCR-based
      restriction assay. In the random population sample the allele frequency of the
      R451Q mutation was 1.9%. Men heterozygous for the R451Q mutation (n = 7) had 27%
      higher CETP activity than age-, body mass index-, smoking- and alcohol
      consumption-matched controls with normal genotype (n = 21; P = 0.003). Women
      heterozygous for the R451Q mutation (n = 7) had 16% lower total cholesterol
      compared to matched controls (n = 21; P = 0.07), but no such difference was
      detected in men. In the random population sample the correlation between plasma
      total cholesterol level and CETP activity was 0.19 (P = 0.044), both in men and
      women. When women with total cholesterol over 5.2 mmol/l were excluded from
      analysis, heterozygotes (n = 4) had plasma CETP activity of 113 nmol/h/ml plasma,
      whereas those of normal genotype (n = 12) had 103 nmol/h/ml plasma, but this
      difference was not statistically significant. Women heterozygous for the R451Q
      mutation and consuming less than 10 g alcohol a week had 23% lower HDL-C compared
      to women with the normal genotype (P = 0.032). In conclusion, we describe a
      mutation in the CETP gene associated with high plasma CETP activity in men and
      with low total cholesterol in women. Further studies are needed to evaluate the
      effect of mutation on the risk of coronary heart disease.

PMID- 9543094
TI  - Iron measures in coronary angiography patients.
AB  - Excess iron has been postulated as a risk factor for coronary artery disease
      (CAD) because of its presence in atherosclerotic lesions, its ability to oxidize
      low density lipoprotein cholesterol (LDLc), and its promotion of oxygen
      reperfusion damage after an ischemic event. Whether iron, indirectly measured by
      its storage protein ferritin and its transport protein transferrin, is related to
      CAD was examined in a consecutive series of white male (n = 457) and female (n =
      114) cardiac patients. Atherosclerosis measures were analyzed in patients grouped
      by tertiles of ferritin. A similar analysis was done with tertiles of
      transferrin. Contrary to expectations, men in the third tertile of ferritin had a
      smaller mean number of stenoses than men in the two lower tertiles (4.9 versus
      5.6 and 5.9; P = 0.027); otherwise, there were no statistically significant
      differences in either number of lesions or extent of arterial narrowing based on
      tertiles of either measure. Separate multiple logistic regression models with
      age, fibrinogen, LDLc and triglycerides as covariates provided no evidence that
      ferritin (odds ratio = 0.88 with 95% C.I. = 0.72-1.07 for men and odds ratio =
      0.79 with 95% C.I. = 0.54-1.16 for women) or transferrin (odds ratio = 0.60 with
      95% C.I. = 0.31-1.16 for men and odds ratio = 1.33 with 95% C.I. 0.52-3.42 for
      women) were important correlates of the presence of atherosclerosis in this
      study.

PMID- 9543095
TI  - Similar response to simvastatin in patients heterozygous for familial
      hypercholesterolemia with mRNA negative and mRNA positive mutations.
AB  - In patients heterozygous for familial hypercholesterolemia, the low-density
      lipoprotein (LDL) cholesterol lowering effect of beta-hydroxy-beta-methylglutaryl
      coenzyme A reductase inhibitors may depend on the nature of the mutation in the
      LDL receptor gene. To test this hypothesis, we compared the response to
      simvastatin, 20 mg daily for 9 weeks, between heterozygous carriers of
      functionally different classes of mutations, i.e. mRNA negative or mRNA positive
      mutations. Out of 116 consecutive, unrelated patients with familial
      hypercholesterolemia, 27 patients were selected for molecular analyses: 14
      patients with mRNA negative and 13 with mRNA positive mutations. Before
      simvastatin treatment, patients with mRNA negative mutations had higher levels of
      LDL cholesterol, lower levels of high-density lipoprotein (HDL) cholesterol and
      significantly more often tendon xanthomas, compared to patients with mRNA
      positive mutations. Simvastatin reduced the mean fasting LDL cholesterol levels
      to a similar percentage in the mRNA negative and mRNA positive patients (37, 36%,
      respectively, 95% CI of difference--8 to 5%, P = 0.2). This effect was similar to
      the 37% decrease observed in our total series of patients with familial
      hypercholesterolemia (n = 116). The increase in mean concentration of HDL
      cholesterol was greater in the mRNA negative group than in the mRNA positive
      group (16, 0%, respectively, 95%, CI of difference 8-25%, P = 0.002) independent
      of the response of total triglycerides to simvastatin. The percentage LDL
      cholesterol lowering response varied among multiple carriers of the same
      mutation, even in the case of mRNA negative mutations. We conclude that the
      percentage LDL lowering response to simvastatin treatment was similar in patients
      with mRNA negative and mRNA positive mutations. Moreover, variation of this
      response within multiple carriers of the same mutation suggests an influence of
      additional factors.

PMID- 9543096
TI  - Effect of apolipoprotein E variants on lipolysis of very low density lipoproteins
      by heparan sulphate proteoglycan-bound lipoprotein lipase.
AB  - Lipoprotein lipase (LPL) is bound to heparan sulphate proteoglycans (HSPG) at the
      luminal surface of endothelium. It is the key enzyme involved in the hydrolysis
      of very low density lipoproteins (VLDL). Prior to lipolysis by LPL, the
      lipoproteins are considered to interact with vessel wall HSPG. Apolipoprotein
      (apo) E is thought to mediate this interaction thereby enhancing the stability of
      the lipoprotein-LPL complex. We hypothesize that apo E mutations may cause a
      diminished interaction of VLDL with HSPG leading to impaired lipolysis of VLDL by
      HSPG-bound LPL. In order to test this hypothesis, lipolysis experiments were
      performed using HSPG-bound LPL. The mean lipolysis rates of VLDL, isolated from
      the apo E2 (Lys146-->Gln) heterozygotes, apo E2 (Arg158-->Cys) homozygotes and
      apo E3-Leiden heterozygotes were 92.3 +/- 10.3 (ns), 77.3 +/- 4.2 (P < 0.05) and
      76.7 +/- 10.0% (P < 0.05), respectively, of that of control VLDL (100.0 +/-
      9.7%). No differences in lipolysis were observed between VLDL from controls and
      VLDL from the same patients if LPL in solution was used. Thus, compositional
      differences alone can not explain the differences in lipolysis rates observed
      with HSPG-bound LPL. In competition experiments, the binding efficiency to HSPG
      LPL of VLDL from the apo E2 (Lys146-->Gln) heterozygotes, apo E2 (Arg158-->Cys)
      homozygotes and apo E3-Leiden heterozygotes was 63 (ns), 41 (P < 0.05) and 35% (P
      < 0.05), respectively of that of control VLDL (100%). We conclude that VLDL
      isolated from apo E2 homozygotes and apo E3-Leiden heterozygotes display
      decreased lipolysis by HSPG-bound LPL due to a defective binding of these
      lipoproteins to the HSPG-LPL complex.

PMID- 9543097
TI  - Oxidative damage of vascular smooth muscle cells by the glycated protein-cupric
      ion system.
AB  - To clarify the mechanism of cellular injury through the nonenzymatic reaction of
      glucose with proteins, we studied the cytotoxic effect of glycated bovine serum
      albumin on cultured smooth muscle cells in the presence of cupric ion. Glycated
      proteins were prepared by incubating bovine serum albumin with 0.5 M D-glucose in
      0.3 M sodium phosphate buffer at 37 degrees C for 2, 4 and 16 weeks (g-BSA-2, g
      BSA-4 and g-BSA-16, respectively). Early glycation products, such as
      fructosamine, were formed more than two weeks after incubation. However, the
      immunoreactivity of glycated proteins to anti-AGE antibody was 12-fold higher in
      g-BSA-16 than in g-BSA-2. Both g-BSA-2 and g-BSA-16 showed a concentration
      dependent cytotoxicity in smooth muscle cells in the presence of 80 microM cupric
      ion by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) dye
      reduction assay and dye exclusion test. Flow cytometry and
      spectrofluorophotometry using dihydrorhodamine 123 showed that the extracellular
      generation of oxidants was dose-dependently enhanced with increasing
      concentrations of g-BSA-2 or g-BSA-16 in the presence of cupric ion. However, no
      difference was observed in the intracellular generation of oxidants between the
      presence and absence of glycated proteins by flow cytometry using 2', 7'
      dichlorofluorescein diacetate. Cytotoxicity and oxidant generation were prevented
      by catalase and tiron, but not by superoxide dismutase or mannitol, a hydroxyl
      radical scavenger. These results indicate that smooth muscle cells may be damaged
      by reactive oxygen species which are produced extracellularly by the interaction
      with the early glycation products and cupric ion, and suggest that hydrogen
      peroxide may be a candidate for reactive oxygen species which contribute to such
      oxidative damage of smooth muscle cells.

PMID- 9543098
TI  - Troglitazone suppresses intimal formation following balloon injury in insulin
      resistant Zucker fatty rats.
AB  - Troglitazone, a thiazolidinedione derivative, overcomes insulin resistance
      through promoting insulin receptor function. However, the effect of the resultant
      enhancement of insulin action on the regulation of cellular proliferation remains
      unknown. We investigated the effect of troglitazone on intimal proliferation
      after balloon injury in insulin-resistant Zucker fatty rats. Troglitazone
      markedly decreased blood glucose and triglyceride levels at the therapeutic
      dosage. The area of neointima significantly decreased in treated animals 2 weeks
      after operation, as compared with the untreated control animals (0.0526 +/-
      0.0292 and 0.115 +/- 0.0354 mm2, respectively). The ratio of neointimal to medial
      area in treated rats (0.75 +/- 0.26) decreased by as much as 53% compared with
      untreated rats (1.40 +/- 0.05). We next examined DNA synthesis in cultured smooth
      muscle cells (SMCs) derived from non-insulin-resistant rats, to assess whether
      troglitazone suppresses the proliferation of vascular SMCs independent of
      metabolic effects. The result showed that troglitazone decreased [methyl
      3H]thymidine incorporation into DNA. In conclusion, treatment with troglitazone
      in Zucker fatty rats resulted in a reduction in neointima formation after balloon
      injury, and also corrected hypertriglyceridemia and hyperglycemia. In addition,
      in vitro studies revealed that the anti-proliferative effect of troglitazone
      stems from its direct action on DNA synthesis rather than any accompanying
      metabolic changes. Therefore, troglitazone seems to be applicable in preventing
      atherosclerosis in patients with insulin resistance.

PMID- 9543099
TI  - Advanced glycosylation end products induced tissue factor expression in human
      monocyte-like U937 cells and increased tissue factor expression in monocytes from
      diabetic patients.
AB  - Tissue factor (TF) plays a central role in the initial activation of the
      extrinsic coagulation pathway and is thought to be involved in the development of
      atherosclerosis and thrombosis. The effect of advanced glycosylation end products
      (AGEs) on TF expression and its mechanism were assessed by flow cytometric
      analysis. Human macrophage-like U937 cells, which were shown to contain mRNA
      encoding the receptors of advanced glycosylation end products (RAGE), expressed
      TF in a dose-dependent manner on incubation with AGE-albumin. AGE-albumin-induced
      TF expression was completely inhibited by the anti-oxidant agents, catalase and
      probucol. TF expression in peripheral monocytes from normal volunteers was also
      increased by AGE-albumin. Finally, TF expression in monocytes from individuals
      with diabetes mellitus, in whom the concentration of circulating AGEs is reported
      to be increased, was higher than that in monocytes from normal controls. These
      results suggest that AGE-induced TF expression in macrophages/monocytes is
      mediated by oxidant stress. AGEs may promote thrombosis and the development of
      atherosclerosis by inducing TF expression in monocytes in patients with diabetes
      mellitus.

PMID- 9543100
TI  - Diabetes mellitus in a new kindred with familial hypobetalipoproteinemia and an
      apolipoprotein B truncation (apoB-55).
AB  - Familial hypobetalipoproteinemia is an autosomal co-dominant disorder, which in a
      minority of cases is due to a truncation producing mutation in the apoB gene. We
      have identified an apoB mutation in a 40-year old hypobetalipoproteinemic man
      with Type II diabetes mellitus. Immunoblotting of plasma revealed a major band
      for apoB-100 and a minor band with estimated size between apoB-52 and apoB-55.
      The proband's 75-year old father with Type II diabetes and a non-diabetic
      daughter also possessed the truncated protein. Direct sequencing of the amplified
      fragment of genomic DNA revealed a C-->T transition at nt 7692 in exon 26 of the
      apoB gene. This substitution yielded a premature stop codon at residue 2495 and
      abolished a BsaI restriction endonuclease site. The identical mutation has been
      described previously; however, the genotypes and ancestors of the kindred were
      different, suggesting that the mutation may have occurred independently. The
      majority of apoB-55 was eluted as particles smaller than LDL-sized apoB-100, and
      floated mostly between the LDL and HDL density range. It is worth noting that
      despite the presence of Type II diabetes, both the proband and his father have
      very low plasma lipid levels and neither have any clinically manifest
      macrovascular complications.

PMID- 9543101
TI  - Monocytic cell adhesion to endothelial cells stimulated by oxidized low density
      lipoprotein is mediated by distinct endothelial ligands.
AB  - Treatment of human umbilical vein endothelial cells (HUVEC) with oxidized low
      density lipoprotein (ox-LDL, 100 microg/ml) for 24 h increased adhesion of human
      monocytic Mono Mac 6 cells from 4.8 +/- 0.9% to 17.6 +/- 2.5% (P < 0.001). The
      effect was dose dependent and first evident at 10 microg/ml ox-LDL. In contrast,
      adhesion of U937 cells was not significantly increased. Mac-1 (CD11b/CD18), a
      monocytic counter-receptor for intercellular adhesion molecule-1 (ICAM-1), that
      also binds to heparin, is present on Mono Mac 6 but not on U937 cells, and may
      thus explain these differences in adhesion. Consistently, ox-LDL induced a 2-fold
      upregulation of ICAM-1 surface expression on HUVEC. The presence of maltose-1
      phosphate or heparin but not monoclonal antibodies (mAbs) to ICAM-1 reduced
      adhesion of Mono Mac 6 cells to untreated HUVEC. Combinations of mAbs to ICAM-1
      with either maltose-1-phosphate or heparin inhibited Mono Mac 6 adhesion to ox
      LDL-stimulated HUVEC by more than 50%, while either alone had no effect. This
      suggests that two distinct endothelial ligands for Mac-1, inducible ICAM-1 and
      carbohydrate-decorated heparin-like proteoglycan structures mediate monocytic
      cell interaction with ox-LDL-treated HUVEC. The stimulating activity in ox-LDL
      could partly be transfered to bovine serum albumin, while lysophosphatidylcholine
      or 8-epi prostaglandin F2alpha produced no stimulatory effects. The inhibition of
      ox-LDL effects with the antioxidant PDTC indicates radicals as possible
      mediators. In conclusion, we show that oxidatively modified LDL induces adhesion
      of monocytic cells, which utilize at least two distinct adhesive receptors on
      endothelium, one being identified as ICAM-1.

PMID- 9543102
TI  - Inhibition of LDL oxidation by a new estradiol receptor modulator compound LY
      139478, comparative effect with other steroids.
AB  - Oxidation of low-density lipoprotein (LDL) is postulated to be essential for the
      development of atherosclerosis. LY-139478 is a new non-steroidal potent estrogen
      analog, but its effects on in vitro LDL oxidation have not been completely
      elucidated. We investigated the ability of LY-139478 to inhibit in vitro copper
      sulfate-mediated LDL oxidation using several methods, including conjugated diene
      (CD) accumulation, relative electrophoretic mobility on agarose gel,
      thiobarbituric acid-reactive substances (TBARS) assay, and superoxide anions
      scavenging activity. The antioxidative potential of LY-139478 was compared to
      testosterone (T), 17-alpha-estradiol (17alphaE), 17-beta-estradiol (17betaE),
      dehydroepiandrosterone (D), and dehydroepiandrosterone-3-sulfate (DS). LY-139478
      was superior to 17alphaE and 17betaE in prolonging the lag phase and decreasing
      the slope and peak concentration of the conjugated diene accumulation, decreasing
      the rate of migration of LDL on agarose gel electrophoresis, and inhibiting the
      production of melonyldialdehyde (MDA) in the TBARS assay. T, D and DS were
      ineffective in all three assays. It was previously shown that when native LDL is
      oxidized by previously oxidized LDL (secondary oxidation) the lag phase is lost
      (Schnitzer et al. Free Rad Res 1995;23:137). LY-139478 was at least 15-fold more
      effective than 17alphaE, and 17betaE in slowing the propagation phase and
      reducing CD accumulation in this secondary oxidation, with 50% inhibition at 10
      microM and 98% inhibition at 100 microM. However, none restored the lag phase. T,
      D and DS were ineffective. Superoxide anion generation was inhibited only by DS
      at high doses (500 microM). These results demonstrate that LY-139478 is an
      effective inhibitor of LDL oxidation and is superior to natural steroidal
      hormones, including 17betaE, in protecting against primary and secondary LDL
      oxidation.

PMID- 9543103
TI  - Hypochlorite-modified low-density lipoprotein stimulates human polymorphonuclear
      leukocytes for enhanced production of reactive oxygen metabolites, enzyme
      secretion, and adhesion to endothelial cells.
AB  - Hypochlorite-oxidized low-density lipoprotein ((-)OCl-LDL) has been shown to
      stimulate various functions of human polymorphonuclear leukocytes (PMNLs).
      Incubation of PMNLs with (-)OCl-LDL (produced by incubation of 0.4 mM LDL
      cholesterol with 1 mM NaOCl for 40 min at 37 degrees C) but not native or copper
      oxidized LDL induced a substantial generation of reactive oxygen species (ROS) as
      measured by means of chemiluminescence with one peak at 10-12 min. Upon
      stimulation with (-)OCl-LDL about 70% of ROS (hydrogen peroxide and superoxide
      anion) were released from the cells into the extracellular environment. The (
      )OCl-LDL-induced increase of the respiratory burst was dependent upon the dose,
      exposure time, and extent of LDL oxidation. Cytochalasin B, an inhibitor of
      phagocytosis, markedly diminished the LDL-induced ROS generation to nearly 40% of
      control values. (-)OCl-LDL enhanced the adhesion of PMNLs to human umbilical
      venous endothelial cells 2.5-fold as compared to native LDL and promoted the
      secretion of the active granule enzymes lysozyme and beta-glucuronidase.
      Together, the results suggest a potential role of LDL-activated PMNLs in
      initiating and/or maintaining the inflammatory process during the early phase of
      atherosclerotic lesion development. Alternatively, PMNLs may also play a
      protective role by phagocytosing oxidized LDL and, thus, preventing further
      detrimental atherogenic effects of oxidized LDL.

PMID- 9543104
TI  - Triglyceride metabolism in heterozygote of Watanabe heritable hyperlipidemic
      rabbit.
AB  - The present study was conducted in order to examine the role of low-density
      lipoprotein (LDL)-receptor activity in very-low-density lipoprotein (VLDL)
      triglyceride metabolism in vivo. Fructose-feeding (10% in drinking water) for 2
      weeks resulted in elevated plasma triglyceride in heterozygote of Watanabe
      heritable hyperlipidemic (WHHL) rabbit (WHHLH) associated with suppressed
      fractional catabolic rate (FCR) of plasma triglyceride, whereas Japanese white
      (JW) rabbit with normal LDL receptor activity showed no remarkable change in
      plasma triglyceride turnover after fructose-feeding, suggesting an involvement of
      LDL receptor activity on triglyceride metabolism. Thereafter, in order to
      stimulate cellular LDL receptor activity, fluvastatin, a new 3-hydroxy-3
      methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor, was administered orally
      (1.52 +/- 0.26 mg/kg) to fructose-fed WHHLH. Significant suppression of
      triglyceride secretion rate (TGSR) was observed after treatment. However, since
      plasma triglyceride level was markedly suppressed, FCR of plasma triglyceride was
      significantly elevated by fluvastatin. Thus, it is speculated from the present
      data that LDL receptor activity is significantly involved in VLDL triglyceride
      metabolism in rabbits.

PMID- 9543105
TI  - Effects of reducing LDL and increasing HDL with gemfibrozil in experimental
      coronary lesion development and thrombotic risk.
AB  - The use of lipid-lowering drugs has been shown to have beneficial effects in
      primary and secondary prevention of cardiovascular disease. Gemfibrozil has shown
      beneficial effects as a lipid lowering agent; however, some proactivating effects
      on platelet function in vitro have been described. We have studied in a porcine
      model of atherosclerosis if gemfibrozil could prevent the early vascular effects
      of a cholesterol-rich diet without inducing platelet activation and, hence, mural
      thrombosis. Pigs were fed for 50 days with a diet rich in saturated fat and
      cholesterol (cho). The longitudinal follow-up study showed that in control
      animals LDL-cho increased significantly up to 181.9 +/- 34.2 mg/dl or 79% of
      total-cho, while HDL-cho was reduced to 19% of total-cho. Gemfibrozil, at average
      therapeutic plasma levels (peak levels of 28 micrograms/ml) [corrected], induced
      a significant reduction in the relative amount of LDL (P < 0.05) and increased
      HDL (P < 0.05). The increase in fibrinogen plasma levels observed in the control
      group due to the dietary intervention (+25%) was prevented in the treated animals
      (-5%). In treated animals, vascular lesions were significantly less severe,
      platelet deposition upon exposure of damaged vessel wall was unchanged and the
      fibrin layer deposited on the damaged vessel wall was significantly reduced over
      control animal values. This short term pharmacologic lipid lowering intervention
      has been able to slow down lesion development and to reduce fibrin formation onto
      lesioned disrupted vascular substrates without increasing platelet mural
      thrombosis.

PMID- 9543106
TI  - C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate
      reductase (MTHFR): its frequency and impact on plasma homocysteine concentration
      in different European populations. EARS group.
AB  - A common polymorphism has been described in the methylenetetrahydrofolate
      reductase (MTHFR) gene, substituting an alanine (A) for a valine (V), where the V
      allele results in a thermolabile enzyme with reduced activity. This polymorphism
      is easily detectable by PCR amplification and digestion with HinfI restriction
      enzyme. We describe the use of the MADGE high throughput genotyping system for
      rapid typing of this polymorphism. Seven hundred and eighty five individuals
      participating in the European Atherosclerosis Research Study II (EARS II), aged
      22-25 from 14 universities in 12 countries across Europe were genotyped for this
      polymorphism. The frequency of the V allele was 0.32 overall (95% CI; 0.30-0.35),
      but was significantly lower in the Baltic countries (0.23; 95% CI; 0.19-0.28)
      compared with the other regions of Europe (0.37; 95% CI; 0.32-0.38) (P < 0.001).
      Individuals homozygous for the V allele had statistically significant (P < 0.001)
      higher plasma homocysteine (16.5 micromol/l) compared with those heterozygous for
      an A allele (10.4 micromol/l) or homozygous for an A allele (10.0 micromol/l).
      This effect was seen in all countries and regions of Europe. Mean plasma
      homocysteine levels were significantly higher in the South compared to the
      Baltic, UK and Middle regions (P = 0.001), but this difference was not explained
      by the difference in the frequency of the V allele in the samples. This
      polymorphism explained 12.3% of the total sample variance in plasma homocysteine,
      other measured factors (smoking, alcohol consumption, systolic blood pressure,
      physical activity) explained 0.7%. This study demonstrates the large and
      consistent impact of the thermolabile MTHFR variant on plasma homocysteine levels
      in different European populations, and shows a regional difference in the levels
      of homocysteine that must be explained by other genetic or environmental factors.

PMID- 9543107
TI  - Glycoxidation in aortic collagen from STZ-induced diabetic rats and its relevance
      to vascular damage.
AB  - Glycoxidation reactions lead to the formation of permanent, irreversible chemical
      modifications and cross-links in protein, such as the glycoxidation products
      carboxymethyllysine (CML) and pentosidine. It has been implicated that CML as
      well as Amadori products play a role in the formation of superoxidative products,
      such as H2O2 and advanced glycosylation endproducts in trapping LDL. Therefore, a
      possible relationship between glycoxidation and lipoperoxidation might exist
      because oxidized lipoprotein, which has been directly linked to atheroma
      formation, could be produced by the superoxidative products released from the
      pathway of CML formation. Using a CML-specific monoclonal antibody (6D12) and a
      specific antiserum against hexitol-lysine (HL), an Amadori product, we studied
      the relationship between glycoxidation and lipoperoxidation by determining the
      aortic CML contents with ELISA and the fluorescence levels of lipoperoxidation
      side products, malondialdehyde (MDA) and hydroxynonenal (HNE) from STZ-induced
      diabetic rats and age-matched control rats. The immunohistochemical and
      ultrastructural changes relevant to glycoxidation and lipoperoxidation were also
      studied. The CML content measured by ELISA in DM rats was significantly higher
      than that in the control rats at 28 weeks (n = 11, P < 0.01). The levels of MDA
      linked and HNE-linked fluorescence in the DM rats increased in a similar way and
      were significantly higher than the levels in control rats at 28 weeks (n = 11,
      both P < 0.01 at 28 weeks). The CML contents correlated with the fluorescence
      levels of both MDA-linked (n = 19, r = 0.638, P < 0.01) and HNE-linked
      fluorescence (n = 19, r = 0.629, P < 0.01) only in the DM rats, but not in the
      control rats. Our immunohistochemical study thus demonstrated that CML was
      initially formed in the aortic media of diabetic rats in the 16th week of
      diabetes, localized primarily in the extracellular matrix surrounding the aortic
      smooth muscle cells after HL occurred early in the 2nd week of diabetes.
      Consequently, a significant increase in the extracellular matrix and decrease in
      the area of the SMCs were observed in the aortic media in the DM rats by a
      morphometrical study. The in vivo results of this study provided the first
      evidence that CML correlated with fluorescence levels of MDA and HNE, and thus
      suggested the existence of a close relationship between glycoxidation and
      lipoperoxidation in vivo. This information is thus considered to shed some new
      light on the etiology of atherogenesis in diabetes.

PMID- 9543108
TI  - Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low
      alpha-linolenic acid.
AB  - Flaxseed (Type I flaxseed) with 51-55% alpha-linolenic acid in its oil and
      richest source of plant lignans, has been shown to reduce hypercholesterolemic
      atherosclerosis by 46% without lowering serum lipids. Antiatherogenic activity
      was claimed to be due to its alpha-linolenic acid and/or lignan content. If alpha
      linolenic acid component of flaxseed is responsible for antiatherogenic activity,
      then, CDC-flaxseed (Type II flaxseed) which has similar oil and lignan content
      but has very little (2-3% of the total oil) alpha-linolenic acid would have no
      antiatherogenic effect. An investigation, therefore, was made of Type II flaxseed
      on high cholesterol diet-induced atherosclerosis and serum lipids [total
      cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL
      C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein
      cholesterol (VLDL-C)] in rabbits. Rabbits were assigned to four groups: Group I,
      Control; Group II, Type II flaxseed diet (7.5 g/kg orally daily); Group III, 1%
      cholesterol diet; Group IV, 1% cholesterol diet supplemented with Type II
      flaxseed (7.5 g/kg orally daily). Blood samples were collected before (0 time)
      and after 4 and 8 weeks of experimental diets for measurement of serum lipids.
      Aorta was removed at the end of 8 weeks for assessment of atherosclerotic
      plaques. Serum TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C were lower in Group IV as
      compared to Group III by 14 and 31%, 17 and 32%, 28 and 34% and 24 and 32%,
      respectively, at 4 and 8 weeks. HDL-C was not affected by Type II flaxseed in
      hypercholesterolemic rabbit. TG and VLDL-C were markedly increased in Group IV as
      compared to Group III. Type II flaxseed reduced the development of
      atherosclerosis by 69%. Histological changes in the atherosclerotic regions were
      qualitatively similar in Groups III and IV. Results indicate that reduction in
      hypercholesterolemic atherosclerosis by Type II flaxseed is due to a decrease in
      serum TC and LDL-C. In conclusion, antiatherogenic activity of Type II flaxseed
      is not due to alpha-linolenic acid.

PMID- 9543109
TI  - Transforming growth factor beta1 induces IL-1 receptor antagonist production and
      gene expression in rat vascular smooth muscle cells.
AB  - Atherosclerosis is an inflammatory-fibroproliferative process that may represent
      a possible milieu in which transforming growth factor-beta (TGF-beta) can be
      involved. Vascular smooth muscle cells (VSMC) may represent a source or a target
      of a large number of growth factors and proinflammatory cytokines, including
      interleukin-1 and its receptor antagonist (IL-1Ra). We tested the effect of TGF
      beta1, on IL-1Ra production and gene expression in rat VSMC cultures. We found a
      significant dose (3-30 ng/ml) and time-dependent (0-48 h) increase in IL-1Ra
      immunoactivity in the supernatant of conditioned medium and cell lysates. The
      maximal effect was observed with TGF-beta at 30 ng/ml and after 24 h incubation
      time, respect to untreated cells (320 +/- 26 vs. 211 +/- 20 pg/ml; P < 0.01).
      Furthermore, TGF-beta1 induced an increased mRNA expression which began at 2 h
      and peaked at 18 h incubation time (about a 6-fold increase with respect to
      unstimulated cells). The effect of TGF-beta1 on IL-1Ra production was completely
      inhibited by an anti-IL-1beta antibody (10 microg/ml) (from 320 +/- 81 to 181 +/-
      46 pg/ml). These experiments suggest that TGF-beta1, potentially produced in the
      vascular wall during atherogenesis, may play a pathophysiological role in the
      autocrine control of IL-1 actions, via VSMC IL-1Ra production.

PMID- 9543110
TI  - Association of smoking and low serum bilirubin antioxidant concentrations.
AB  - This study sought to examine the association between cigarette smoking and serum
      bilirubin antioxidant concentrations in 715 middle-aged men undergoing coronary
      angiography. The study involved 153 current smokers, 251 who quit smoking and 311
      who never smoked. Serum bilirubin concentrations were divided into the following
      quartiles; 0.20-0.57, 0.58-0.73, 0.74-0.95 and 0.96-3.26 mg/dl. The percentage of
      individuals within each quartile were as follows; current smokers (42, 22, 24,
      12), former smokers (22, 27, 23, 28), nonsmokers (16, 28, 27, 29). A total of 42%
      of the current smokers had bilirubin concentrations in the lowest quartile
      compared to 16% of the nonsmokers. Also, 12% of the current smokers had bilirubin
      concentrations in the highest quartile compared to 29% in the nonsmoking group.
      The Mantel-Haenszel chi-square test for association between ordered categorical
      variables was 30.6 (P < 0.0001). Subdividing the subjects according to maximum
      percent stenosis on angiography (< 10, 10-49, 50-100%) revealed a significant
      inverse association between smoking and bilirubin (< 0.01) within each subset.
      The data shows that smoking is associated with decreased serum bilirubin
      concentrations. In addition, it supports the hypothesis that cigarette smoking
      may increase the risk of coronary artery disease by lowering antioxidant
      concentrations and raising oxidized lipid and lipoprotein concentrations.

PMID- 9543111
TI  - Elevated lipoprotein(a) levels and small apo(a) isoforms are compatible with
      longevity: evidence from a large population of French centenarians.
AB  - Epidemiological studies have shown lipoprotein(a) (Lp(a)) to be an independent
      risk factor for cardiovascular disease. Lp(a) is a cholesterol-rich, low-density
      lipoprotein (LDL)-like particle to which a large glycoprotein, apolipoprotein(a)
      (apo(a)) is attached. Plasma Lp(a) levels are highly genetically determined and
      influenced to a minor degree by environmental factors. In an effort to determine
      whether Lp(a) might be associated with longevity, we have evaluated Lp(a) levels
      and apo(a) isoform sizes in a population of French centenarians (n = 109)
      compared to a control group (n = 227). The mean age of centenarians was 101.5 +/-
      2.4 years while the control group was 39.4 +/- 7.2 years. Plasma levels of total
      cholesterol and triglyceride were within the normal range in both centenarian and
      control subjects. Lp(a) levels were higher in centenarians (both male and female)
      than in the normolipidemic control group (mean Lp(a) level = 0.33 +/- 0.42 and
      0.22 +/- 0.27 mg/ml, respectively, P < 0.005). The distribution of apo(a)
      isoforms was significantly shifted towards small isoform size in the centenarian
      population as compared to the controls (54.4 and 41.4% of isoforms < or = 27
      kringles (kr), respectively, P = 0.04). Nonetheless, the apo(a) size distribution
      in centenarians did not entirely explain the high Lp(a) levels observed in this
      population. Factors other than apo(a) size, and which may be either genetic or
      environmental in nature, appear to contribute to the elevated plasma Lp(a) levels
      of our centenarian population. We conclude therefore that high plasma Lp(a)
      levels are compatible with longevity.

PMID- 9543112
TI  - Lipid profiles reflecting high and low risk for coronary heart disease:
      contribution of apolipoprotein E polymorphism and lifestyle.
AB  - To elucidate the role of modifiable factors and the apolipoprotein E polymorphism
      in explaining lipid profiles reflecting low, average and high risk for coronary
      heart disease, we selected subjects from a large population-based study. Subjects
      with low total cholesterol (TC) (< 15th percentile) and high HDL-cholesterol
      levels (> 85th percentile) were randomly selected (n = 99) and represent subjects
      with a low risk lipid profile. Additionally, 95 subjects with total and HDL
      cholesterol levels in the 15% around the population-median (median risk lipid
      profile) and 100 subjects with high TC (> 85th percentile) and low HDL
      cholesterol levels (< 15th percentile) (high risk lipid profile) were selected.
      Compared with E3/3 subjects, the likelihood for a low risk lipid profile was
      considerably higher (odds ratio 14.3; 2.6-79) in female, but not in male E2
      carriers (1.5; 0.3-6.7). Smoking and alcohol consumption were independently
      associated with a low risk lipid profile in both genders, physical inactivity
      only in women. The odds ratio for a high risk lipid profile was elevated in male
      E4-carriers (4.9; 1.1-23) only. In addition to the E4 isoform, smoking and
      physical inactivity, overweight was the main determinant for a high risk lipid
      profile (odds ratio 16.8; 3.4-82). Male overweight E4-carriers had a 50 times
      higher likelihood of a high risk lipid profile than E3/3 men of normal weight. In
      women, only overweight was independently associated with a high risk lipid
      profile. Our results suggest that both modifiable factors and the apolipoprotein
      E polymorphism contribute to a lipid profile, reflecting low, average and high
      risk for coronary heart disease, but effects may be gender-specific.

PMID- 9543113
TI  - A little more on lipoprotein profile in peripheral arterial disease.

PMID- 9543114
TI  - Susceptibility to oxidation and physicochemical properties of LDL in insulin
      dependent diabetics.

PMID- 9543115
TI  - Clinical review 93: Autoimmune polyglandular syndrome type 1.

PMID- 9543116
TI  - Bone turnover during lactation--can calcium supplementation make a difference?

PMID- 9543117
TI  - Biochemical markers of calcium and bone metabolism during 18 months of lactation
      in Gambian women accustomed to a low calcium intake and in those consuming a
      calcium supplement.
AB  - The effect of 18 months of lactation on indexes of calcium and bone metabolism
      was studied in 60 Gambian women accustomed to a very low calcium intake. Half the
      women consumed a calcium supplement from 10 days postpartum for 52 weeks
      (supplement, 714 mg Ca/day; total Ca intake, 992 +/- 114 mg/day), and half
      consumed placebo (total Ca intake, 288 +/- 128 mg/day). Fasting blood and 24-h
      urine samples were collected at 1.5, 13, 52, and 78 weeks of lactation and
      analyzed for calciotropic hormones (intact PTH, 1,25-dihydroxyvitamin D, and
      calcitonin), bone turnover markers (osteocalcin, bone alkaline phosphatase, and
      urinary deoxypyridinoline), and plasma minerals (calcium and phosphate). The
      first months of lactation were associated with increased bone turnover and plasma
      phosphate, and decreased PTH and 1,25-dihydroxyvitamin D. These effects
      diminished by 52 weeks, although breast milk volumes remained high. The Gambians
      had higher PTH, 1,25-dihydroxyvitamin D, and bone formation than British women
      with a greater customary calcium intake. None of the biochemical indexes was
      affected by calcium supplementation, with the possible exception of bone alkaline
      phosphatase (-29% at 52 weeks; P = 0.015). These data demonstrate that lactation
      associated changes in calcium and bone metabolism are physiological and are
      independent of dietary calcium supply in women with very low calcium intakes.

PMID- 9543118
TI  - Does growth hormone have a role in the management of children with nongrowth
      hormone deficient short stature and intrauterine growth retardation?

PMID- 9543119
TI  - Short stature associated with intrauterine growth retardation: final height of
      untreated and growth hormone-treated children.
AB  - Short term studies have demonstrated the acceleration of growth velocity after
      the administration of GH in short children born with intrauterine growth
      retardation (IUGR). We report the final heights of 70 IUGR children whose short
      stature was attributed to idiopathic GH deficiency (peak plasma GH <10 ng/mL at 2
      provocative tests) and treated with GH at a mean dosage of 0.4 +/- 0.1 U/kg x
      week during an average of 4.6 +/- 2.5 yr. They were compared to a control group
      of 40 untreated short children born with IUGR, without GH deficiency. At the time
      of evaluation, age, auxological data, and pubertal status were similar in the 2
      groups (height, -2.9 +/- 0.8 and -2.8 +/- 0.7 SD score). Final heights were
      comparable in both groups of children (-2 +/- 0.7 and -2.2 +/- 1.1 SD score). A
      multivariate analysis identified 4 independent predictors of final height, namely
      target height, age and body mass index at evaluation, and GH treatment. Treatment
      was associated with a gain of 0.6 SD score, suggesting a final height gain of
      about 3.4 cm. Fifty-three of 70 treated children were reevaluated after
      completion of growth, and 43 of 53 had a peak plasma GH level of 10 ng/mL or
      more. Auxological characteristics of these 53 patients were not different from
      those of nonreevaluated patients. We believe that the transient character of the
      GH deficiency in most patients and the nonstringent initial criteria used for the
      diagnosis of GH deficiency render the spontaneous growth potentials identical in
      the 2 groups of patients. Our data, therefore, suggest that GH treatment at this
      dosage has a limited effect on the final height of short children born with IUGR.

PMID- 9543120
TI  - Comparison of final heights of growth hormone-treated vs. untreated children with
      idiopathic growth failure.
AB  - We measured adult heights (Ht) of 94 healthy GH-sufficient children (peak GH > 10
      ng/mL, polyclonal RIA) whose Ht at presentation were more than 2 SD below the
      mean for chronological age, with normal weight-to-Ht ratios, normal body
      proportions, and pathologic growth velocity for chronological age. Group 1 (n 36,
      6 females) received standardized doses (0.3 mg/kg x week) of GH (mean duration =
      41 months), while group 2 (n = 58, 17 females) received no treatment. Our
      conclusion was that the mean final Ht SD score in the GH-treated group (-1.5) was
      significantly greater than in the untreated group (-2.1); P < .001. Genetic
      predisposition to short stature was evident in both groups: the midparental Ht SD
      score was -1.1 in the treated and -1.0 in the untreated group. Midparental Ht was
      met or exceeded by 42% of the GH-treated group but only 15% of the untreated
      group. Final Ht was not significantly different from predicted Ht, except from GH
      treated girls, who exceeded their predicted Ht. Although the mean Ht gains (6.8
      cm in girls and 3 cm in boys) were modest and variable, GH treatment provided
      significantly better Ht outcomes for the majority of children with idiopathic
      growth failure.

PMID- 9543121
TI  - Calcimimetics--new drugs with the potential to control hyperparathyroidism.

PMID- 9543122
TI  - Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel
      calcimimetic agent.
AB  - Parathyroid carcinoma is one cause of primary hyperparathyroidism, a condition in
      which there is hypercalcemia and dysregulated hypersecretion of PTH. In normal,
      and in some neoplastic parathyroid cells, PTH secretion is mediated by the cell
      surface calcium-sensing receptor. We describe the first therapeutic use of a
      novel molecule, a calcimimetic, that has agonist action at the calcium-sensing
      receptor. A 78-yr-old man with parathyroid carcinoma was admitted with
      hypercalcemia, markedly elevated PTH, and a change in mental status. He was
      treated for 17 days with conventional therapy, which included saline hydration,
      furosemide, pamidronate, and calcitonin. This was ineffective, and on hospital
      day 18, calcimimetic at a dose of 50 mg, orally, every 6 h was added. On hospital
      day 25, the dose was increased to 100 mg, orally, every 6 h, and on hospital day
      30, saline and furosemide were discontinued. He was discharged on hospital day
      40. With several dose adjustments, he has been treated with monotherapy
      calcimimetic for over 600 days and has not required any other interventions for
      his parathyroid carcinoma. Mean daily precalcimimetic treatment values of serum
      ionized calcium and PTH were 1.83 mmol/L and 872 pg/mL, respectively. During
      hospitalization, at the lower dose of calcimimetic, calcium and PTH decreased to
      1.67 mmol/L and 538 pg/mL; with the higher dose they further decreased to 1.51
      mmol/L and 444 pg/mL. Since discharge, and despite increasing levels of PTH,
      serum calcium has remained high, but lower than the admission level and acutely
      responsive to changes in calcimimetic doses. This compound, a calcimimetic, the
      first of a new class of compounds with activity at the calcium-sensing receptor,
      has been used to treat a patient with parathyroid carcinoma. During 2 yr of
      treatment, no adverse clinical effects have been observed, and it appears to have
      been effective at controlling hypercalcemia.

PMID- 9543123
TI  - Leptin and puberty.

PMID- 9543125
TI  - Therapeutic controversy: Thyroid surgery--the choice.

PMID- 9543126
TI  - Normal postprandial lipemia and chylomicron clearance in offspring of parents
      with early coronary artery disease.
AB  - To assess the importance of postprandial lipemia and delayed chylomicron
      clearance as early atherogenic risk factors, 60 male offspring of parents with
      early coronary artery disease (CAD) and 41 controls were administered a fat-rich
      meal containing vitamin A. There were no significant differences between CAD
      positive (CAD+) offspring and CAD-negative controls for areas under the
      postprandial curves for triglyceride and plasma, chylomicron, and chylomicron
      remnant retinyl palmitate. Older CAD+ offspring, aged 31-45 yr, had significantly
      increased very low density lipoprotein (VLDL) cholesterol, VLDL triglyceride,
      VLDL apoprotein B, and areas under postprandial curves for triglyceride and
      plasma, chylomicron, and chylomicron remnant retinyl palmitate than younger CAD+
      offspring, aged 15-30 yr. Correcting for waist/hip ratio eliminated significant
      differences between the two groups for VLDL and areas under the triglyceride and
      chylomicron remnant curves, but this was not the case for the insulin sensitivity
      index. We conclude that neither increased postprandial lipemia nor abnormalities
      of chylomicron clearance are important early atherogenic risk factors in this
      population. An increase in age is associated with increased VLDL and postprandial
      lipemia and decreased chylomicron remnant clearance. This is due mainly to an
      increase in the waist/hip ratio and not to a change in insulin sensitivity.

PMID- 9543124
TI  - The impact of reversible gonadal sex steroid suppression on serum leptin
      concentrations in children with central precocious puberty.
AB  - Serum leptin concentrations increase during childhood in both sexes. During
      sexual maturation, levels rise further in girls, but decrease in boys. These data
      suggest that testosterone either directly suppresses leptin levels or induces
      changes in body composition that result in lower leptin concentrations. To
      examine further the relationship between sex steroids and leptin, we performed a
      longitudinal study in children with central precocious puberty (28 girls and 12
      boys) before, during, and after discontinuation of GnRH agonist-induced pituitary
      gonadal suppression. Nighttime and daytime leptin levels were measured to
      determine whether the activity of the pituitary-gonadal axis affects their
      diurnal variation. In the boys, suppression of testosterone increased leptin
      levels, whereas resumption of puberty was associated with decreased leptin levels
      [3.5 +/- 0.8 vs. 9.5 +/- 3.1 ng/dL (P = 0.005) and 12.2 +/- 4.5 vs. 7.0 +/- 2.6
      ng/dL (P = 0.012), respectively]. Serum leptin levels did not change in the girls
      with alteration of the pituitary-ovarian axis and consistently exceeded those in
      boys. Nighttime levels were consistently greater than daytime values by an
      average of 38.3% in the girls and 29.4% in the boys. These serial observations
      during reversible pituitary-gonadal suppression suggest that testosterone
      decreases leptin concentrations, but that estrogen, at least in this childhood
      model, has no discernible effect. In addition, our data indicate that the
      presence of the diurnal rhythm in leptin concentrations is independent of the
      state of the reproductive axis.

PMID- 9543127
TI  - Suppressibility of plasma adrenocorticotropin by hydrocortisone: potential
      usefulness in the diagnosis of Cushing's disease.
AB  - Repeatedly normal cortisol suppressibility by dexamethasone in 2 patients with
      Cushing's disease led to the present study of the prevalence of this phenomenon
      in 58 patients with otherwise incontrovertible evidence of Cushing's disease.
      Because as many as 23% of these patients manifested this phenomenon, we
      investigated the suppressibility of plasma ACTH: 1) during i.v. infusion of
      hydrocortisone, after a priming dose (7 mg), at 3 mg/h in 8 patients and 8 normal
      controls; and 2) for 2 h, after oral hydrocortisone, 0.25 mg/kg, in 13 patients
      and 16 controls. The data showed invariable suppression of plasma ACTH to < or =
      10 pg/mL (< or = 2.2 pmol/L) after 120 min of the infusion or at 90 min after
      oral hydrocortisone in 16 fasting normal subjects given oral hydrocortisone
      between 0800 and 0830 h. Plasma ACTH exceeded 10 pg/mL (2.2 pmol/L) at the same
      times in 14/14 patients with active Cushing's disease, including 3 patients whose
      cortisol suppressibility by dexamethasone had been misleadingly normal and in 4/7
      patients with intermittent hypercortisolism. Occasional variations in plasma
      cortisol elevations after the oral dose require that plasma cortisol
      concentration be monitored at 60 min after the oral hydrocortisone dose, because
      the present evidence supports the validity of the conclusion that a plasma ACTH
      concentration below 10 pg/mL excludes Cushing's disease only when plasma cortisol
      concentration at 60 min lies between 16 and 38 microg/dL. Further evaluation of
      ACTH suppressibility by cortisol would be worthwhile, to confirm its potential
      value in facilitating positive diagnosis of Cushing's disease when dexamethasone
      suppressibility seems misleading.

PMID- 9543128
TI  - Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin
      measurement, and prognostic significance in patients with differentiated thyroid
      carcinoma.
AB  - The prevalence of circulating thyroid autoantibodies (TgAb or antithyroid
      peroxidase) was increased nearly 3-fold in patients with differentiated thyroid
      cancers (DTC) compared with the general population (40% vs. 14%, respectively).
      Serum TgAb (with or without antithyroid peroxidase) was present in 25% of DTC
      patients and 10% of the general population. Serial postsurgical serum TgAb and
      serum Tg patterns correlated with the presence or absence of disease.
      Measurements of serum Tg were made in 87 TgAb-positive sera by a RIA and two
      immunometric assay (IMA) methods to study TgAb interference. TgAb interference,
      defined as a significant intermethod discordance (>41.7% coefficient of
      variation) between the Tg RIA and Tg IMA values relative to TgAb-negative sera,
      was found in 69% of the TgAb-positive sera. TgAb interference was characterized
      by higher Tg RIA vs. IMA values and was, in general, more frequent and severe in
      sera containing high TgAb concentrations. However, some sera displayed marked
      interference when serum TgAb was low (1-2 IU/mL), whereas other sera with very
      high TgAb values (>1000 IU/mL) displayed no interference. An agglutination method
      was found to be too insensitive to detect low TgAb concentrations (1-10 IU/mL)
      causing interference. Exogenous Tg recovery tests were an unreliable means for
      detecting TgAb interference. Specifically, the exogenous Tg recovered varied with
      the type and amount of Tg added and the duration of incubation employed. Further,
      recoveries of more than 80% were found for some sera displaying gross serum
      RIA/IMA discordances. The measurement of serum Tg in DTC patients with
      circulating TgAb is currently problematic. It is important to use a Tg method
      that provides measurements that are concordant with tumor status. IMA methods are
      prone to underestimate serum when TgAb is present, increasing the risk that
      persistent or metastatic DTC will be missed. The RIA method used in this study
      provided more clinically appropriate serum Tg values in the group of TgAb
      positive patients with metastatic DTC. Furthermore, as serial serum TgAb
      measurements paralleled serial serum Tg RIA measurements, TgAb concentrations may
      be an additional clinically useful tumor marker parameter for following TgAb
      positive patients. Disparities between serial serum Tg and TgAb measurements
      might alert the physician to the possibility of TgAb interference with the serum
      Tg measurement and prompt a more cautious use of such data for clinical decision
      making.

PMID- 9543129
TI  - Randomized trial of effect of cyclical etidronate in the prevention of
      corticosteroid-induced bone loss. Ciblos Study Group.
AB  - Osteoporosis is a well-recognized adverse effect of corticosteroid therapy. This
      study aimed to investigate the effect of etidronate, intermittent cyclical
      therapy, in the prevention of corticosteroid-induced bone loss. Patients with
      various medical conditions starting high-dose corticosteroid therapy were
      enrolled in the study. The treatment had to be expected to continue for at least
      12 months with the initial 90 days at a mean daily dose of at least 7.5 mg of
      prednisone, with subsequent treatment of at least 2.5 mg/day. One hundred
      seventeen patients were randomly assigned oral etidronate 400 mg/day, or placebo,
      for 14 days, followed by 76 days of oral calcium carbonate (500 mg elemental
      calcium), cycled over 12 months. The primary outcome measure was the difference
      in percent change from baseline in bone mineral density of the lumbar spine
      between the groups at the end of year 1. Secondary measures included changes in
      femur bone density and in biochemical markers of bone remodeling. The mean (+/-
      SEM) lumbar spine bone density changed 0.30 +/- 0.61% and -2.79 +/- 0.63% in the
      etidronate and placebo groups, respectively. The mean difference between groups
      after 1 yr was 3.0 +/- 0.84% (P = 0.004). The changes in the femoral neck and
      great trochanter were not different between the groups. There was a decrease in
      pyridinium crosslinks, significant from baseline at both 6 and 12 months, in the
      etidronate group. Osteocalcin increased in the placebo group, and difference
      between groups was -25.07 +/- 14.89% (P = 0.032) and -34.68 +/- 19.77% (P =
      0.051), at 6 and 12 months respectively. There was no significant difference
      between the groups in number of adverse experiences, including gastrointestinal
      disorders. Etidronate intermittent cyclical therapy prevents lumbar vertebral
      bone loss in patients starting high-dose corticosteroid therapy.

PMID- 9543130
TI  - Quality of life among formerly treated childhood-onset growth hormone-deficient
      adults: a comparison with unaffected siblings.
AB  - Several studies have investigated the quality of life (QOL) of GH-deficient (GHD)
      adults who, as children, had been treated with GH. Variable findings are probably
      related to sample heterogeneity and disparate research methodologies and designs,
      particularly the choice of control or comparison groups. In addition to comparing
      a relatively large sample to questionnaire norms, the present study is the first
      to compare the QOL adjustment of GHD patients to that of same sex siblings. A
      total of 140 former patients (76% of those eligible; mean age, 26 yr; n = 95
      isolated GHD, n = 45 multiple pituitary hormone deficiencies; 117 males and 23
      females) and 53 same sex siblings (84% participation), 18 yr and older,
      participated in the telephone questionnaire survey. The majority of interviews
      with GHD patients (78%) and siblings (87%) were conducted blind to the subject's
      clinical status. Comparisons between GHD patients and norms for standardized
      questionnaires indicated both better and worse functioning in several domains. In
      contrast, very limited differences were detected between GHD cases and same sex
      siblings. Isolated GHD patients were functioning better than those with multiple
      pituitary hormone deficiencies, but the effect sizes of these differences in most
      areas were relatively small. Adult height and degree of growth over the course of
      GH therapy were generally unrelated to QOL outcomes. Findings from the present
      study underscore the importance of selecting unbiased control/comparison groups
      in evaluating psychological outcomes among GHD adults.

PMID- 9543131
TI  - High prevalence of polycystic ovaries and associated clinical, endocrine, and
      metabolic features in women with previous gestational diabetes mellitus.
AB  - The prevalence of polycystic ovaries, according to ultrasonography, and
      associated clinical, endocrine, and metabolic features were investigated in women
      with previous gestational diabetes mellitus (GDM). Thirty-four women with GDM 3-5
      yr before the investigation and 36 controls with uncomplicated pregnancies,
      selected for similar age, parity, and date of delivery, were investigated. The
      women with previous GDM showed a higher prevalence of polycystic ovaries [14 of
      34 (41%) vs. 1 of 36 (3%); P < 0.0001], hirsutism (P < 0.01), irregular menstrual
      cycles (P < 0.01), and a higher body mass index (BMI; P < 0.001) than the
      controls. Five women (15%) with previous GDM had developed manifest diabetes
      (excluded in comparisons of metabolic variables). After dividing the women with
      previous GDM into subgroups according to ovarian appearance, the 2 subgroups
      showed similar glucose tolerance and prevalence of diabetes, whereas the women
      with polycystic ovaries were younger (mean +/- SD, 33.3 +/- 1.4 vs. 38.2 +/- 1.1;
      P < 0.01), had higher truncal-abdominal/femoral fat ratio according to skin folds
      (P < 0.05), had higher concentrations of androstenedione (P < 0.01) and
      testosterone (P < 0.01), and had a higher LH/FSH ratio (P < 0.01), lower levels
      of GH (P < 0.01), higher levels of triglycerides (P < 0.05) and cholesterol (P <
      0.05) in very low density lipoprotein, all independent of age and BMI, and had a
      higher prevalence of pregnancy-induced hypertension (50% vs. 15%; P < 0.05)
      during the index pregnancy compared with the women with normal ovaries. The group
      of women with GDM showed a lower early insulin release after glucose (i.v.
      glucose tolerance test) for their degree of insulin resistance (euglycemic
      hyperinsulinemic clamp) compared with controls (P < 0.05). In the two subgroups,
      insulin sensitivity was lower in the polycystic ovaries group, independent of BMI
      (P < 0.05), than in the group with normal ovaries. In conclusion,
      ultrasonographic, clinical and endocrine signs of polycystic ovary syndrome were
      much increased in women with a history of GDM. Compared with the women with
      normal ovaries and previous GDM, those with polycystic ovaries formed a distinct
      subgroup that may be more prone to develop various features of the insulin
      resistance syndrome. Both groups showed a similarly disturbed balance between
      beta-cell activity and insulin sensitivity, but in women with polycystic ovaries,
      insulin resistance may be the dominant component.

PMID- 9543132
TI  - Influence of exogenous atrial natriuretic peptide on the pituitary-adrenal
      response to corticotropin-releasing hormone and vasopressin in healthy men.
AB  - Atrial natriuretic peptide (ANP) has been considered a potential candidate
      participating in the inhibitory control of pituitary-adrenal secretory activity.
      Here, we investigated the influence of ANP, infused at two different doses and
      over infusion intervals of two different durations, on the release of ACTH and
      cortisol after stimulation with CRH and with combined administration of CRH and
      vasopressin (VP). In young healthy men, three experiments were conducted. In Exp
      I, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and
      after a 45-min period of ANP infusion at a rate of 4.4 microg/min (starting 15
      min before CRH injection). In Exp II, ACTH/cortisol secretory responses to CRH
      (50 microg) were examined during and after a 90-min infusion period of ANP
      administered at rates of 4.4 and 8.8 microg/min. In Exp III, ANP was infused at a
      rate of 4.4 microg/min over 90 min, but instead of CRH, a combined administration
      of CRH (50 microg) and VP (0.5 IU infused within 5 min) was employed to stimulate
      ACTH/cortisol release. ANP diminished pituitary-adrenal secretory responses
      within the first hour after stimulation with exogenous secretagogues. Thereafter,
      the effect of ANP turned in the opposite direction, with distinctly enhanced
      concentrations of ACTH and cortisol during the third hour after stimulation. The
      inhibitory effect of ANP during the first hour of the pituitary-adrenal response
      was more pronounced on concentrations of cortisol than ACTH and was also more
      pronounced after combined administration of CRH/VP than after stimulation with
      CRH alone. Increasing the dose of ANP enhanced the late stimulatory effect on
      ACTH/cortisol release, thereby terminating the early period of inhibited
      ACTH/cortisol release more abruptly. The late stimulatory effect was enhanced
      with prolonged infusion of ANP. In addition, it was associated with reduced
      hematocrit, increased urine volumes collected, increased heart rate, and enhanced
      plasma VP concentrations. Together, these changes suggest that the late
      stimulatory effect of ANP on ACTH/cortisol release reflects an effect secondary
      to its hypovolemic actions. This stimulatory effect originating from peripheral
      systemic actions of ANP after exogenous administration appears to override a more
      direct inhibitory action of the peptide on pituitary-adrenal secretory activity.
      Therefore, we would expect that with localized release into portal hypophyseal
      blood the inhibitory component of the action of ANP on pituitary-adrenal
      secretory activity prevails.

PMID- 9543133
TI  - Comparison of effects of tamoxifen and toremifene on bone biochemistry and bone
      mineral density in postmenopausal breast cancer patients.
AB  - Antiestrogens are used in the treatment, and sometimes even in the prophylaxis,
      of breast cancer. Tamoxifen is the most commonly used antiestrogen, but
      toremifene is gaining in popularity. We compared here the effects of tamoxifen
      and toremifene on bone metabolism and density in 30 postmenopausal patients with
      breast cancer, who were randomized to receive tamoxifen (20 mg/day, n = 16) or
      toremifene (40 mg/day, n = 14) for 1 yr. Biochemical markers of bone resorption
      [urinary hydroxyproline, serum cross-linked carboxyterminal telopeptide of type I
      collagen, urinary cross-linked aminoterminal telopeptide of type I collagen
      (NTx)] and bone formation [serum bone-specific alkaline phosphatase, osteocalcin,
      and aminoterminal and carboxyterminal propeptide of type I procollagen] were
      assessed before treatment and at 6 and 12 months of the antiestrogen regimen.
      Bone mineral density (BMD) in the lumbar spine and proximal femur (neck,
      trochanter, and Ward's triangle) was measured using dual-energy x-ray
      absorptiometry before treatment and at 12 months of treatment. Urinary NTx
      decreased after 6 months' use of tamoxifen (mean fall: 33%) and of toremifene
      (mean fall: 16%). Use of tamoxifen was associated with a significant decrease in
      osteocalcin (mean fall: 25%) and aminoterminal propeptide of type I procollagen
      (mean fall: 22%), whereas toremifene failed to influence these markers. Tamoxifen
      increased BMD, on average, by 2% in the lumbar spine, 1% in the femoral neck, and
      5% in Ward's triangle. Toremifene failed to increase BMD at any site measured,
      and in contrast, a slight trend toward a fall (-0.3 to -0.9%) in BMD was seen in
      patients treated with toremifene. Falls in urinary NTx, from baseline to 6
      months, correlated significantly with changes in the lumbar spine BMD (r = -0.57,
      P = 0.0002) in the whole patient series. We conclude that tamoxifen (20 mg/day)
      increases BMD in postmenopausal breast cancer patients, whereas toremifene (40
      mg/day) merely prevents the increasing age-associated fall in BMD. More prolonged
      studies on bone metabolism, comparing these two antiestrogens, are needed; but
      even now, clinicians should be aware of these differences between tamoxifen and
      toremifene.

PMID- 9543134
TI  - A single midnight serum cortisol measurement distinguishes Cushing's syndrome
      from pseudo-Cushing states.
AB  - Cushing's syndrome (CS) may be difficult to distinguish from pseudo-Cushing
      states (PCS) based on physical findings or urinary glucocorticoid excretion. As
      the lack of diurnal variation in serum cortisol is characteristic of CS, we
      studied whether diurnal cortisol determinations could discriminate CS from PCS.
      Two hundred and sixty-three patients were evaluated: 240 had CS, and 23 had PCS.
      Urine was collected for 24 h for measurement of cortisol and 17
      hydroxycorticosteroids (17OHCS). Blood was drawn at 2300, 2330, 0000, 0030, and
      0100 h and at 0600, 0630, 0700, 0730, and 0800 h the next morning for serum
      cortisol determination. The main outcome measure was the sensitivity of these
      parameters for the diagnosis of CS at 100% specificity. A midnight cortisol value
      greater than 7.5 microg/dL correctly identified 225 of 234 patients with CS and
      all PCS patients. This sensitivity (96%) was superior to that obtained for any
      other measure, including urinary cortisol (45%), 17OHCS (22%), any other
      individual cortisol time point (10-92%), the morning (23%) or the evening (93%)
      cortisol mean, and the ratio (11%) of morning to evening values. We conclude that
      at 100% specificity, a single serum cortisol value above 7.5 microg/dL at
      midnight discriminates CS from PCS with higher sensitivity than 24-h urinary
      cortisol or 17OHCS, or other individual or combined measures of serum cortisol.

PMID- 9543135
TI  - Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a
      phase I study in children.
AB  - Administration of GH-releasing peptide-2 (GHRP-2) represents a potential mode of
      therapy for children of short stature with inadequate secretion of GH. Requisite
      information to determine the dosing route and frequency for GHRP-2 consists of
      the pharmacokinetics (PK) and pharmacodynamics (PD) for this compound, neither of
      which have been previously evaluated in children. The purpose of this study was
      to characterize the PK and PD of GHRP-2 in children with short stature. Ten
      prepubertal children (nine boys and one girl; 7.7 +/- 2.4 yr old) received a
      single 1 microg/kg i.v. dose of GHRP-2 over 1 min, followed by repeated (n = 9)
      blood sampling over 2 h. GHRP-2 and GH were quantitated by specific RIA methods.
      PK parameters were calculated from curve fitting of GHRP-2 and GH vs. time data.
      Posttreatment plasma GH concentrations (normalized for pretreatment values) were
      used as the effect measurement. PD parameters were generated using the sigmoid
      Emax model. Disposition of GHRP-2 best fit a biexponential function. GHRP-2 PK
      parameters (mean +/- SD) were: alpha = 13.4 +/- 9.7 h(-1), beta = 1.3 +/- 0.3 h(
      1), t(1/2beta) = 0.55 +/- 0.14 h, AUC(0-infinity) = 2.02 +/- 1.37 ng/mL x h, Cmax
      = 7.4 +/- 3.8 ng/mL, plasma clearance = 0.66 +/- 0.32 L/h x kg, and apparent
      volume of distribution = 0.32 +/- 0.14 L/kg. PK parameters for GH were:
      appearance rate constant = 5.9 +/- 3.1 h(-1), elimination t(1/2) = 0.37 +/- 0.15
      h, lag time = 0.05 +/- 0.01 h, Cmax = 50.7 +/- 17.2 ng/mL, Tmax = 0.42 +/- 0.16
      h, and AUC(0-infinity) = 47.9 +/- 26.1 ng/mL x h. PD parameters for GHRP-2 were:
      Ke0 = 1.13 +/- 0.94 h(-1), gamma = 13.15 +/- 9.44, E0 = 6.63 +/- 4.86 ng/mL (GH),
      Emax = 67.5 +/- 23.5 ng/mL (GH), and EC50 = 1.09 +/- 0.59 ng/mL. We concluded
      that 1) GHRP-2 produced a predictable and significant (i.e. compared to
      pretreatment values) increase in plasma GH concentrations; 2) the PK-PD link
      model enabled quantitative assessment of GHRP-2 modulation of serum GH levels;
      and 3) definition of the EC50 for GHRP-2 will enable PD and PK evaluations of
      extravascular dosing regimens for children.

PMID- 9543136
TI  - Response to androgen treatment in a patient with partial androgen insensitivity
      and a mutation in the deoxyribonucleic acid-binding domain of the androgen
      receptor.
AB  - Supplemental androgen therapy has enhanced virilization in only a few patients
      with partial androgen insensitivity (PAIS). We herein report on virilization in a
      patient with PAIS and a point mutation in the DNA-binding domain of the androgen
      receptor. At the age of 19 yr, the patient sought medical attention because of
      undervirilization. Endocrine findings were typical for androgen insensitivity,
      but 5alpha-reductase activity and androgen binding characteristics in fibroblasts
      cultured from genital skin were normal. In an attempt to improve virilization,
      high dose testosterone enanthate treatment (250 mg by i.m. injection once a week)
      was begun. After 3.5 yr of this treatment, marked promotion of virilization was
      achieved, i.e. lowering of voice, male pattern secondary hair distribution,
      marked growth of beard and coarse body hair, increase in phallic size, increase
      in bone mineral density, and decrease in mammary gland size. In addition, serum
      lipid levels were not affected. To our knowledge this is the first documentation
      of successful treatment in a patient with PAIS and a point mutation in the DNA
      binding domain of the androgen receptor.

PMID- 9543137
TI  - Elevated connexin-43 expression in term human myometrium correlates with elevated
      c-Jun expression and is independent of myometrial estrogen receptors.
AB  - Just previous to the onset of parturition, a number of genes such as the one that
      codes for connexin-43 (Cx43) gap junction protein are induced in the myometrium.
      We have shown previously that activation of protein kinase C in human myometrial
      cultured cells leads to an up-regulation of cx43 transcription through an
      activating protein-1 element in the 5'-flanking promoter. Analyses were now
      performed on extracts of term myometrial tissue to test for an association
      between the up-regulation of cx43 expression and the expression of transcription
      factors and steroid hormone receptors that might regulate cx43 expression at
      term. Immunoblot analyses were performed on extracts of term myometrial tissue
      from women receiving elective or indicated cesarean sections to test for an
      association between the up-regulation of cx43 expression and the up-regulation of
      expression of the transcription factors c-Jun, c-Fos, and Sp1, which have cognate
      binding elements in the cx43 5'-flanking promoter. Immunoblot analysis,
      immunohistochemistry, and receptor binding assays were also performed to analyze
      the levels of progesterone receptors (PR) and estrogen receptors (ER) in the same
      term myometrial tissue, and these were compared to the levels in nonpregnancy
      myometrial tissue. The levels of PR were consistently 2- to 3-fold higher in term
      myometrial tissue than in nonpregnancy values and did not fluctuate during the
      menstrual cycle as did ER levels. Surprisingly, in term myometrium, ER was barely
      detectable by immunoblot and had whole cell diffuse staining by
      immunohistochemistry. In addition, very low levels of estrogen binding were
      observed in the term myometrial tissue. Treatment of primary myometrial cultures
      containing ER with estrogen for 3 or 48 h did not result in up-regulation of c
      Jun or c-Fos proteins or in trans-activation from the proximal cx43 promoter with
      the activating protein-1 element. In contrast, an activated form of c-Jun protein
      was 10- to 18-fold higher in term myometrial tissue that also had elevated cx43
      expression compared to c-Jun levels in term myometrial tissue with low cx43
      expression. Likewise, c-Fos and Sp1 levels were 2-4 fold higher in term
      myometrial tissue with elevated cx43 expression. Although c-Fos and Sp1 proteins
      could be detected by immunoblot in myometrial tissue from nonpregnant women, c
      Jun and Cx43 proteins could not. In summary, these results suggest that up
      regulation of human myometrial cx43 gene expression at term involves induction of
      primarily c-jun expression through a mechanism that does not directly involve
      myometrial ER or the loss of PR. Peptide hormones that activate protein kinase
      cascades, such as the protein kinase C cascade, may be important to signal the
      onset of labor in humans.

PMID- 9543138
TI  - Growth hormone (GH)-releasing peptide-6 requires endogenous hypothalamic GH
      releasing hormone for maximal GH stimulation.
AB  - GH-releasing peptide-6 (GHRP-6) is a potent GH secretagogue that releases GH by
      uncertain mechanisms. To assess whether GHRH is required for GH release by GHRP-6
      in humans, we used the specific antagonist to GHRH (N-Ac-Tyr1,D-Arg2)GHRH(1
      29)NH2 (GHRH Ant). We have previously shown that GHRH-Ant (400 microg/kg) blocked
      the GH response to 0.33 and 3.3 microg/kg boluses of GHRH by 95% and 81%,
      respectively. Nine healthy men between the ages of 20 and 30 yr were studied on
      two occasions. They received either saline or GHRH-Ant (400 microg/kg, i.v.) at
      0840 h, followed by GHRP-6 (1 microg/kg, i.v. bolus) at 0900 h. Blood was sampled
      every 10 min from 0800-1100 h. GH responses were measured as the maximal increase
      over the baseline GH concentration and as the area under the curve. GHRH-Ant
      eliminated most of the GH response to GHRP-6 [maximal increase over the baseline
      GH concentration, 33.8 +/- 4.8 vs. 6.2 +/- 1.8 microg/L (mean +/- SEM; P <
      0.0001); area under the curve, 1701 +/- 278 vs. 376 +/- 113 microg/min x L (P <
      0.001)]. These data show that endogenous GHRH is necessary for most of the GH
      response to GHRP-6 in humans.

PMID- 9543139
TI  - 17Beta-hydroxysteroid dehydrogenase type 1 in normal breast tissue during the
      menstrual cycle and hormonal contraception.
AB  - Our purpose was to assess 17beta-hydroxysteroid dehydrogenase (17HSD) type 1
      protein expression in normal breast tissue during the menstrual cycle and
      hormonal contraception. We analyzed 17HSD type 1 protein expression by
      immunohistochemistry during the regular menstrual cycle (n = 12) and hormonal
      contraception (n = 7) in women undergoing reduction mammoplasty. 17HSD type 1
      protein was detected in normal breast epithelial cells throughout the menstrual
      cycle and in all women using hormonal contraception. Mean 17HSD type 1 staining
      intensity was higher in alveolar epithelial cells in women using hormonal
      contraception (2.14) than in untreated women (1.25; P < 0.04). For ducts, this
      difference approached significance (2.29 vs. 1.41; P = 0.06). There was a
      negative correlation between serum estradiol (E2) levels and 17HSD type 1 protein
      expression for both alveolar (r(s) = -0.68; P = 0.004) and ductal (r(s) = -0.75;
      P = 0.002) breast epithelial cells. Enhanced 17HSD type 1 protein expression
      might increase the conversion to E2 in normal breast tissue during hormonal
      contraception. The negative correlation between serum E2 levels and 17HSD type 1
      suggests this enzyme to be one of the regulatory mechanisms of intratissue E2
      concentration in normal breast tissue.

PMID- 9543140
TI  - Expression and secretion of inhibin and activin in normal and neoplastic uterine
      tissues. High levels of serum activin A in women with endometrial and cervical
      carcinoma.
AB  - Inhibins and activins are growth factors belonging to the transforming growth
      factor-beta) family and are known to influence cell proliferation and
      differentiation. Because transforming growth factor-beta is involved in
      physiological and tumoral changes of uterine tissues, the present study aimed to
      evaluate whether human normal and neoplastic endometrial and cervical epithelial
      cells express and secrete inhibin A, inhibin B, and activin A. To test this
      hypothesis, different approaches were used. By RT-PCR, the expression of specific
      messenger RNAs (mRNAs) for the inhibin alpha, activin betaA and betaB subunits,
      and activin receptor type II and type IIB was investigated: 1) in primary
      cultures of endometrial (stroma and epithelium) or cervical (epithelium) cells
      from healthy women; and 2) in specimens of endometrial or cervical carcinoma. To
      demonstrate a possible secretion of the proteins, dimeric inhibin A, inhibin B,
      and activin A were measured in culture medium of normal epithelial or stromal
      endometrial cells and in uterine washing fluid of healthy women or patients with
      endometrial adenocarcinoma. Levels of the proteins were also measured in serum of
      women with endometrial or cervical carcinoma. Cultured endometrial stromal or
      epithelial cells and epithelial cervical cells expressed inhibin alpha, activin
      betaA and betaB, and activin receptor type II and type IIB mRNAs. The same
      finding was obtained in specimens of endometrial or cervical carcinomas. Dimeric
      inhibin A, inhibin B, and activin A were measured in culture medium of both
      endometrial and cervical cells. In particular, resulting activin A levels were
      significantly higher in epithelial than in stromal cultured endometrial cells (P
      < 0.01). Dimeric proteins were also detected in the washing fluid of the uterine
      cavities of healthy women (controls) and with endometrial adenocarcinoma, in
      which higher activin A levels were found (P < 0.01 vs. controls). Women with
      endometrial carcinoma showed serum activin A levels significantly higher than
      healthy controls (P < 0.01), which significantly decreased after surgical removal
      of endometrial or cervical tumors (P < 0.01). The present study, for the first
      time, showed that inhibin A, inhibin B, and activin A, as well as activin
      receptors, are expressed in normal and neoplastic human uterine tissues. A
      secretion of activin A from tumoral cells into systemic circulation is suggested
      by the observation that the high levels in serum of patients with endometrial or
      cervical carcinoma decreased after the surgical removal of the tumor.

PMID- 9543141
TI  - Interleukin-8 induces proliferation of endometrial stromal cells: a potential
      autocrine growth factor.
AB  - Proliferation of endometrium is dependent on sex steroid hormones, but specific
      growth factors are likely to play an important role in regulating this process. A
      number of cytokines and growth factors are synthesized in the endometrium in
      response to sex steroid hormones and act to regulate endometrial function.
      Endometrial cells produce interleukin-8 (IL-8) both in vivo and in vitro. We
      hypothesized that IL-8, a neutrophil chemoattractant/activating factor and a
      potent angiogenic agent that has been shown to stimulate growth in other cell
      types, may directly stimulate proliferation of endometrial cells. We first
      investigated the effect of IL-8 and mouse antihuman-IL-8 neutralizing antibody on
      endometrial stromal cell proliferation using both a colorimetric assay and
      thymidine uptake. We then investigated the modulation of endometrial stromal cell
      IL-8 production and proliferation by antisense oligonucleotides specific for IL
      8. There was a concentration-dependent increase of cell proliferation with IL-8
      (2-fold at 1 ng/mL; P < 0.01 between control and concentrations above 0.01 ng/mL)
      and a concentration-dependent inhibition of cell proliferation with anti-IL-8
      antibody (to 30% of the control at 1 microg/mL; P < 0.01 between control and
      concentrations above 0.1 microg/mL). IL-8 antisense oligonucleotide treatment
      decreased IL-8 production by endometrial stromal cells in culture as well as cell
      proliferation when it is compared with scrambled (nonsense) oligonucleotide
      treatment (P < 0.01). Addition of IL-8 (1 ng/mL) reversed the proliferation
      inhibitory effect of IL-8 antisense oligonucleotides. We propose that IL-8 may
      act as an autocrine growth factor in the endometrium, and suggest that it may
      also play a role in the pathogenesis of endometriosis.

PMID- 9543142
TI  - No effect of growth hormone on serum insulin-like growth factor binding protein-3
      proteolysis.
AB  - Increased proteolysis of insulin-like growth factor binding protein (IGFBP)-3 is
      seen in several pathophysiological conditions and may represent an important
      mechanism for the regulation of insulin-like growth factor bioavailability. It
      has previously been suggested that proteolysis of IGFBP-3 is dependent on the GH
      status. To investigate this, IGFBP-3 proteolysis was measured in three groups of
      subjects: 1) GH-deficient patients before and after GH replacement (n = 14); 2)
      healthy subjects before and after 14 days of GH administration (n = 7); and 3)
      acromegalic patients before and after treatment with a long-acting SRIH analogue
      (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investigated by Western
      immunoblotting. No difference was detected in pretreatment samples, and GH
      treatment in GH-deficient subjects or octreotide treatment in acromegalic
      subjects had no impact on in vivo proteolysis. In contrast, GH administration to
      healthy subjects caused a 21% increase in in vivo proteolysis (P = 0.0008). In
      vitro IGFBP-3 proteolysis was investigated by incubation of serum with 125I
      rhIGFBP-3, followed by SDS-PAGE. In pretreatment samples, the percentage of
      proteolyzed 125I-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects), 11 +/- 1%
      (healthy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-deficient
      vs. acromegalic subjects). Treatment had no effect on in vitro proteolysis. We
      conclude that GH status has no major impact on IGFBP-3 protease activity in
      serum.

PMID- 9543143
TI  - How much insulin-like growth factor I (IGF-I) circulates? Impact of
      standardization on IGF-I assay accuracy.
AB  - There is a significant systematic difference between the normal range obtained
      from ethylenediamine tetraacetate plasma samples using the Genentech total
      insulin-like growth factor I (IGF-I) RIA and normal ranges for other total IGF-I
      RIAs. To determine whether the quality of the assay standard was the cause of
      this systematic difference, we analyzed commercially available preparations of
      recombinant human IGF-I (rhIGF-I) typical of those used as IGF-I immunoassay
      standards along with our own well characterized rhIGF-I assay standard. For the
      commercial standards, high performance liquid chromatography-derived purities
      were low, and some vendor-assigned protein concentrations were inconsistent with
      values from quantitative amino acid analysis. The Genentech rhIGF-I assay
      standard was highly pure and quantitatively correct. However, the poor quality of
      some commercial rhIGF-I preparations was not the primary reason for the
      systematic discrepancy between the Genentech total IGF-I RIA normal range and
      most other normal ranges. Most assays for total IGF-I are calibrated against the
      WHO International Reference Reagent (IRR) for IGF-I Immunoassays (87/518). The
      Genentech total IGF-I RIA is not calibrated against WHO IRR 87/518. The protein
      content assigned to WHO IRR 87/518 was a consensus value from a multicenter
      collaborative study. Physicochemical analyses showed that WHO IRR 87/518 is Met(
      1)-IGF-I of low purity (44%), and that the assigned protein content is higher
      than the value determined by quantitative amino acid analysis. Thus, assays that
      are calibrated against WHO IRR 87/518 will report total IGF-I concentrations in
      excess of actual values. We believe that calibration against WHO IRR 87/518 is
      the cause of the systematic discrepancy between the Genentech IGF-I assay normal
      range and most other normal ranges, and that much of the plasma IGF-I
      concentration data in the literature are of questionable accuracy.

PMID- 9543144
TI  - The modulation of the human sodium iodide symporter activity by Graves' disease
      sera.
AB  - The transport of iodide into the thyroid, catalyzed by the Na+/I- symporter
      (NIS), is the initial and rate-limiting step in the formation of thyroid
      hormones. To study the basic characteristics of the human (h) NIS, we have
      established a Chinese hamster ovary cell line stably expressing the hNIS (CHO
      NIS9). In agreement with previous work on the rat NIS, iodide uptake in these
      cells was initiated within 2 min of the addition of 131I, reaching a plateau
      after 30 min. Both perchlorate and thiocyanate inhibited iodide uptake in a dose
      dependent manner, with inhibition evident at concentrations of 0.01 and 0.1
      micromol/L, respectively, and reaching complete inhibition at 20 micromol/L and
      500 micromol/L, respectively. Ouabain, which blocks the activity of the Na+/K+
      adenosine triphosphatase, also inhibited iodide uptake in a dose-dependent
      manner, starting at concentrations of 100 micromol/L and reaching maximum
      inhibition at 1600 micromol/L, indicating that iodide uptake in these cells is
      sodium dependent. CHO-NIS9 cells were further used to study 88 sera from patients
      with Graves' disease, for iodide uptake inhibitory activity, which were compared
      with sera from 31 controls. Significant iodide uptake inhibition was taken as any
      inhibition in excess of the mean + 3 SD of the results with the control sera. On
      this basis, 27 (30.7%) of the Graves' sera, but none of the controls, inhibited
      iodide uptake in CHO-NIS9. IgGs from these patients also inhibited iodide uptake,
      indicating that this inhibitory activity was antibody mediated. In summary, we
      have established a CHO cell line stably expressing the hNIS and shown that
      antibodies in GD sera can inhibit iodide uptake in these cells. This further
      emphasizes the role of NIS as a novel autoantigen in thyroid immunity.

PMID- 9543145
TI  - Soluble intercellular adhesion molecule-1 (sICAM-1) concentrations in Graves'
      disease patients followed up for development of ophthalmopathy.
AB  - It is commonly recognized that a few patients with Graves' disease (GD) develop
      an overt ophthalmopathy, although most of them show subclinical extraocular
      muscle enlargement by appropriate imaging techniques. At present, it is not
      possible to identify the subgroup of GD patients with subclinical retroorbital
      connective involvement. Recently, it has been shown that increase of soluble
      intercellular adhesion molecule-1 (sICAM-1) serum levels is correlated to
      clinical activity score in active Graves' ophthalmopathy (GO) patients with or
      without hyperthyroidism, suggesting that sICAM-1 serum values could reflect the
      degree of ocular inflammatory activity. The aim of this longitudinal study was to
      evaluate sICAM-1 serum levels in GD patients without clinical ophthalmopathy and
      to assess their possible relationship with occurrence of GO. We measured sICAM-1
      serum levels in 103 initially hyperthyroid GD patients without clinical
      ophthalmopathy and in 100 healthy subjects. All patients were treated with
      methimazole for 2 yr. Sera were collected from all patients before treatment and
      then monthly for the first 6 months of therapy, every 2 months in the following 6
      months, and finally at the end of the follow-up study. Patients developing GO
      were excluded from the follow-up at the onset of ophthalmopathy. During the
      follow-up 17 GD patients (16.5%, group 1) developed overt eye involvement (14 as
      active inflammatory ophthalmopathy and 3 as ophthalmopathy without clinical
      retroorbital connective inflammation) and 86 (83.5%, group 2) did not. At start
      of the study, the mean of sICAM-1 serum concentrations did not differ
      significantly between the 2 groups, but it was significantly higher than in
      controls in both groups. No significant correlation between serum sICAM-1
      concentrations and free thyroid hormone levels was found in the 2 groups of
      patients. During the follow-up study, a further increase of sICAM-1 serum levels
      was observed in 12 of the 14 patients (85.7%) of group 1 who developed active
      inflammatory ophthalmopathy not only at the onset but also before clinical GO
      appearance. On the contrary, the 3 patients of group 1 that developed
      ophthalmopathy without clinical retroorbital inflammation did not show any
      further increase of sICAM-1 levels at every time of follow-up in comparison with
      the starting values, even if their sICAM-1 levels were always higher than in
      normal controls. Finally, group 2 patients showed significantly decreased sICAM-1
      levels throughout the follow-up period when compared with the starting values,
      although they were still significantly higher than in controls. These results
      indicate that a further increase of sICAM-1 serum levels before the onset of
      clinical ophthalmopathy may be a marker of subclinical retroorbital connective
      inflammation in GD patients. Therefore, our study suggests that serial
      determinations of sICAM-1 serum levels could help to identify and trace at the
      right time those GD patients prone to developing active inflammatory
      ophthalmopathy.

PMID- 9543146
TI  - Regulation of the glycosylated beta-lactoglobulin homolog, glycodelin [placental
      protein 14:(PP14)] in the baboon (Papio anubis) uterus.
AB  - In vitro studies indicate that glycodelin (PP14) synthesis by the human
      endometrium increases dramatically at the time of implantation and early
      pregnancy. It has been postulated that this protein may have an immunosuppressive
      function. Due to the limitations associated with in vivo studies in the human,
      this study was undertaken to study the regulation of the baboon glycodelin
      homolog in vivo during the menstrual cycle and early pregnancy. In nonpregnant
      baboons, between days 10-12 postovulation (n = 3) the mid and apical regions of
      the glandular epithelium showed a distinct punctate staining pattern, which
      increased between days 12-18 of pregnancy (n = 3). Between days 25-60 of
      pregnancy, staining intensity in the glandular epithelium decreased. The decrease
      was more apparent at the implantation site compared with the nonimplantation
      site. The immunostaining correlated with the synthesis of radiolabeled baboon
      glycodelin in explant culture. Northern blot analysis demonstrated two messenger
      RNA (mRNA) transcripts [1.0 and 1.7 kilobases (kb)] in the baboon uterus compared
      with a single 1.0-kb transcript in the human, and mRNA expression was consistent
      with protein localization and synthesis. The protein and mRNA expression was
      consistently higher in the deeper glands of the functionalis and basalis during
      early pregnancy. Because the increased expression of glycodelin in the baboon
      endometrium coincided with peak levels of CG, a simulated pregnant baboon model
      was used to confirm hormonal regulation. Exogenous human CG (hCG) followed by
      estrogen and progesterone treatment in intact and ovariectomized baboons up
      regulated glycodelin expression between days 18-25 postovulation (n = 10). By day
      32 postovulation (n = 3), glycodelin synthesis decreased. Estrogen and
      progesterone treatment in the absence of exogenous hCG did not result in an
      increase of glycodelin synthesis. Analysis of uterine flushings from hCG-treated
      animals revealed that a minimum of 7 days of hCG treatment was required for
      glycodelin to be detectable in the uterine lumen. These studies indicate that a
      posttranslationally modified glycodelin homolog is synthesized by the baboon
      uterus during early pregnancy and appears to be regulated directly by CG. This
      pattern of synthesis is comparable with that observed with in vitro studies in
      the human. Because glycodelin expression is associated with CG secretion, we
      suggest that this protein may have a functional role during implantation in the
      primate. Thus, the baboon may serve as a nonhuman primate model to elucidate the
      function of this protein in vivo.

PMID- 9543147
TI  - Effect of glucose on production and release of proinsulin conversion products by
      cultured human islets.
AB  - Isolated human islets were examined for the rates of conversion and release of
      newly formed (pro)insulin-like peptides. The rate of proinsulin (PI) conversion
      was 2-fold slower in human beta-cells (t(1/2) = 50 min) than in rat beta-cells
      (t(1/2) = 25 min). During the first hour following labeling of newly synthesized
      proteins, PI represented the main newly formed hormonal peptide in the medium;
      its release was stimulated 2-fold over the basal level by 20 mmol/L glucose.
      During the second hour, newly synthesized hormone was mainly released as insulin,
      with 10- to 20-fold higher rates at 20 mmol/L glucose. Prolonged preculture of
      the islets at 20 mmol/L glucose did not delay PI conversion, but markedly
      increased the release of newly formed PI, des(31,32)-PI, and insulin at both low
      and high glucose levels. Our data demonstrate that 1) the release of PI provides
      an extracellular index for the hormone biosynthetic activity of human beta-cells;
      2) an acute rise in glucose exerts a stronger amplification of the release of
      converted hormone than in that of nonconverted hormone; and 3) prolonged exposure
      to high glucose levels results in an elevated basal release of converted and
      nonconverted PI; this elevation is not associated with a delay in PI conversion,
      but is attributed to the hyperactivated state of the human beta-cell population,
      which was recently found to be responsible for an elevation in basal rates of
      hormone synthesis. These in vitro observations on human beta-cells provide a
      possible explanation for the altered circulating (pro)insulin levels measured in
      nondiabetic and noninsulin-dependent diabetic subjects.

PMID- 9543148
TI  - Expression of c-kit messenger ribonucleic acid in human oocyte and presence of
      soluble c-kit in follicular fluid.
AB  - The c-kit protooncogene receptor and its ligand stem cell factor (SCF) regulate
      the proliferation and survival of germ cells as well as hematopoietic cells and
      melanocytes. In adult rodent ovary, c-kit and SCF play important roles in
      follicular development. However, little information about c-kit in the human
      ovary is available. In this study, we examined the expressions of c-kit messenger
      ribonucleic acid (mRNA) and c-kit protein in human oocytes, granulosa cells, and
      follicular fluid obtained from the women who underwent in vitro fertilization or
      laparoscopic examination. Expression of c-kit mRNA was detected by RT-PCR in the
      oocytes and granulosa cells. Western blot analysis showed the presence of soluble
      c-kit protein in the follicular fluid, and lower levels of c-kit protein were
      detected in the granulosa cells and the supernatant of granulosa cell cultures.
      The concentration of soluble c-kit in follicular fluid measured by enzyme-linked
      immunosorbent assay showed significant correlation with fluid volume and
      follicular fluid concentrations of estradiol, testosterone, and androstenedione.
      In summary, we found for the first time the presence of c-kit mRNA and soluble c
      kit protein in human oocytes and follicular fluid. The results suggested that in
      human ovary, c-kit may play an important role in follicular development.

PMID- 9543149
TI  - Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth
      retardation on serum leptin concentrations.
AB  - The aim of this study was to investigate the ontogeny of serum leptin
      concentrations during the second half of gestation and at birth in small for
      gestational age and normal fetuses and newborns. Serum leptin concentrations were
      measured in arterial cord blood of fetuses (n = 79) and newborns (n = 132), with
      or without intrauterine growth retardation, at 18-42 weeks gestation. Serum
      leptin was detectable in fetal cord blood in all subjects as early as 18 weeks
      gestation. Leptin levels dramatically increased after 34 weeks gestation. In
      newborns, serum leptin concentrations were positively correlated with body weight
      (P < 0.001) and body mass index (P < 0.001). Newborns with intrauterine growth
      retardation had significantly lower serum leptin values (P < 0.001) than those
      with normal growth, and leptin levels were only positively correlated with body
      mass index (P < 0.001). These results suggest that the development of adipose
      tissue and the accumulation of fat mass are the major determinants of fetal and
      neonatal serum leptin levels. In addition, a gender difference, with higher
      leptin concentrations in female fetuses, was observed during the last weeks of
      gestation and was confirmed at birth regardless of growth status, suggesting that
      a sexual dimorphism already exists in utero.

PMID- 9543150
TI  - The daily cortisol production reinvestigated in healthy men. The serum and
      urinary cortisol production rates are not significantly different.
AB  - We have measured the urinary cortisol production rate (uCPR) simultaneously with
      the serum cortisol production rate (sCPR) in four healthy men within a period of
      3 days. uCPR, determined by isotope dilution of 11-oxoetiocholanolone was
      compared with sCPR, which was measured in three different ways (a, b, c). Blood
      was sampled at 10-min intervals for 24 h, and deconvolution analysis was applied
      to the cortisol concentrations. The daily serum cortisol production per liter,
      multiplied by the distribution volume yielded sCPR. The measurement methods are
      characterized as follows: a) the secretion and elimination terms were free; b)
      like method a, but with the input of the rate constants alpha and beta into the
      elimination function; c) the average 24-h cortisol concentration was multiplied
      by the metabolic clearance rate. uCPR was 25.4 +/- 4.7 [range: 21.3-31.4]
      micromol/(m2 x day), sCPR (method a) was 28.8 +/- 4.5 [range: 23.5-34.3]
      micromol/(m2 x day), sCPR (method b) was 27.9 +/- 8.1 [range: 18.5-37.7]
      micromol/(m2 x day), and sCPR (method c) was 29.3 +/- 4.8 [range: 22.7-33.2]
      micromol/(m2 x day). uCPR did not significantly differ from each of the 3 sCPR
      values (P > 0.30; > 0.46; and > 0.06, respectively). The patterns of the cortisol
      secretory rates in the present and previous studies do not necessarily represent
      the physiological process of the secretory bursts. We conclude that the estimated
      CPR, being 25-30 micromol/(m2 x day) [9-11 mg/(m2 x day)], can serve as a
      guideline for glucocorticoid replacement dose and that the urinary route to
      measure CPR is preferred because of its relative ease.

PMID- 9543151
TI  - Suppression of cell proliferation and induction of apoptosis in uterine leiomyoma
      by gonadotropin-releasing hormone agonist (leuprolide acetate).
AB  - Cell proliferation and apoptosis in uterine leiomyoma were investigated during
      therapy with GnRH agonist (GnRHa). Patients with uterine leiomyomas were injected
      with 3.75 mg GnRHa (depot leuprolide acetate) at intervals of 4 weeks and
      underwent hysterectomy or myomectomy at the 2nd, 4th, 8th, 12th, or 16th week of
      GnRHa therapy. Tissue sections of leiomyomas from these patients and from control
      patients (control patients received no GnRHa therapy) were stained with the Ki-67
      antibody or by an in situ DNA 3'-end labeling method, and numbers of Ki-67
      immunostained cells and DNA 3'-end-labeled cells per cm2 were examined as indices
      of cell proliferation and apoptosis, respectively. The number of Ki-67
      immunostained cells/cm2 in leiomyomas at the 2nd week of the GnRHa therapy was
      comparable with that of control patients. However, it decreased to a level less
      than one forth that of control patients at the 4th week, and it remained at
      similar low levels at the 8th, 12th, and 16th week. The number of DNA 3'-end
      labeled cells/cm2 in leiomyomas of control patients and in leiomyomas at the 2nd,
      8th, 12th, and 16th weeks of GnRHa therapy were at low levels but, at the 4th
      week, was at an extremely high level (about 5 times more than that of control
      patients). The present results indicate that GnRHa therapy suppresses cell
      proliferation and causes a transient increase in apoptosis in uterine leiomyomas.

PMID- 9543152
TI  - Developmentally regulated responses of human granulosa cells to insulin-like
      growth factors (IGFs): IGF-I and IGF-II action mediated via the type-I IGF
      receptor.
AB  - In experimental animal models, insulin-like growth factors (IGFs) have been found
      to be more potent stimulators of ovarian function than insulin. In human theca
      cells, however, insulin, IGF-I, and IGF-II have similar effects on androgen
      production. The relative effects of insulin and IGFs on human granulosa cell
      steroidogenesis is unknown. Furthermore, it is unclear whether effects of IGF-II
      on steroidogenesis are mediated by the type-I or type-II IGF receptor. The
      effects of insulin, IGF-I, and IGF-II on human granulosa cell steroidogenesis
      were compared in vitro. As expected, insulin, IGF-I, and IGF-II enhanced
      steroidogenesis. Previously, IGF-II has been shown to enhance granulosa cell
      steroid production after insulin preincubation. In this study, an effect of IGF
      II, independent of insulin priming, also was observed. In granulosa cell cultures
      from small antral follicles (< or = 13 mm), insulin and IGF-I stimulated steroid
      production to a similar degree, whereas IGF-II was less effective. In contrast,
      IGFs were more effective than insulin (IGF-I > IGF-II > insulin) in granulosa
      cells isolated from preovulatory follicles. IGF-I and IGF-II actions were
      mediated via the type-1 IGF receptor. The increased responsiveness of mature
      granulosa cells to IGFs may be an important mechanism by which granulosa cells
      increase their steroidogenic output in the preovulatory follicle.

PMID- 9543153
TI  - Pima Indian males have lower beta-adrenergic sensitivity than Caucasian males.
AB  - The sympathetic nervous system controls cardiovascular homeostasis and regulates
      energy metabolism. Pima Indians, a population with a low prevalence of
      hypertension and a high prevalence of obesity, have low sympathetic nervous
      activity, compared with Caucasians. Preliminary findings suggest that they may
      also have a low beta-adrenergic sensitivity. We studied beta-adrenergic
      sensitivity in 87 nondiabetic normotensive individuals [52 Pima Indians (35
      males/17 females) and 35 Caucasians (24 males/11 females)], matched for age and
      body weight. Chronotropic sensitivity to beta-adrenergic stimulation was assessed
      by the dose of isoproterenol necessary to increase heart rate by 25 beats per
      minute [chronotropic dose-25 (CD25)]. Despite a similar basal heart rate and
      arterial blood pressure, Pimas tended to have lower beta-adrenergic sensitivity
      than Caucasians (CD25 = 2.37 +/- 2.27 vs. 1.57 +/- 1.38 microg, P = 0.07; mean +/
      SD). This difference was significant in males (CD25 = 3.03 +/- 2.39 vs. 1.85 +/-
      1.56 microg, P = 0.02) but not in females (CD25 = 1.01 +/- 1.17 vs. 0.96 +/- 0.61
      microg, P = 0.99). In males only, CD25 was positively correlated to percent body
      fat (r = 0.36, P < 0.01). After adjustment for percent body fat, beta-adrenergic
      sensitivity was still significantly lower in Pima than in Caucasian males (CD25 =
      3.44 +/- 2.24 vs. 2.57 +/- 1.60 microg, P = 0.05). In conclusion, our data
      suggest that increased adiposity is accompanied by decreased beta-adrenergic
      sensitivity in males only. However, at each level of adiposity, Pima Indian males
      have lower beta-adrenergic sensitivity than Caucasian males. In combination with
      a low sympathetic nervous system activity, a reduced beta-adrenergic sensitivity
      may contribute to the low prevalence of hypertension and the high prevalence of
      obesity observed in Pima Indians.

PMID- 9543154
TI  - Proteins in the heat shock-70 family specifically bind 25-hydroxyvitamin D3 and
      17beta-estradiol.
AB  - Most New World primates evolved to express a form of compensated resistance to
      steroid hormones from the gonads and adrenal glands as well as to the
      hydroxylated vitamin D3 prohormone, 25-hydroxyvitamin D3 (25OHD3), and the
      vitamin D hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] originating from the
      liver and kidney, respectively. We recently demonstrated that this form of
      resistance is associated with the overexpression of a novel member of the 70-kDa
      heat shock protein (hsp-70) molecular chaperone family, which we have termed the
      intracellular vitamin D binding protein (IDBP). In the current report we more
      closely examine the ligand-binding capability of purified IDBP and two other
      mammalian hsp-70 family members, heat-inducible (hsp-70) and constitutively
      expressed (hsc-70) hsp-70 proteins. Purified IDBP, hsp-70, and hsc-70 all bound
      25OHD3 with relatively high affinity; the mean Kd for 25OHD3 ranged from 0.5-2.2
      nmol/L (rank order: IDBP > or = hsp-70 > or = hsc-70). By Scatchard analysis,
      high affinity, specific binding of 1,25-(OH)2D3 was not reproducibly observed for
      any of the three members of the hsp-70 family. Unlike purified IDBP, hsc-70 and
      hsp-70 were also competent binders of the gonadal steroid 17beta-estradiol (mean
      Kd for 25OHD3, 2.5 and 6.6 nmol/L by hsc-70 and hsp-70, respectively), but not of
      two other gonadal hormones, progesterone and testosterone. These data suggest
      that IDBP is relatively specific for 25OHD3 and that additional hsp-70-like
      binding proteins are present in unpurified New World primate cell extracts that
      are specific for 1-hydroxylated vitamin D metabolites as well as other gonadal
      steroid hormones.

PMID- 9543155
TI  - Detection of CD40 on human thyroid follicular cells: analysis of expression and
      function.
AB  - Thyroid follicular cells (TFC) are a common target of autoimmune attack, but the
      role they play in inciting and maintaining this attack is unclear. TFC express
      cytokines, adhesion molecules, and class I and II major histocompatibility
      complex molecules, but without additional signals that costimulate T cells, they
      may down-regulate, rather than stimulate, T cell function. In this report, we
      have investigated whether TFC can express the CD40 molecule, which plays a
      crucial role in the reciprocal two-way communication between T and B cells. We
      have shown by immunohistochemistry and flow cytometry that CD40 is expressed by
      TFC in vivo and in vitro in both autoimmune and nonautoimmune glands. CD40
      expression was up-regulated by interleukin-1alpha and interferon-gamma, but not
      by TSH. Although there was no significant effect of CD40 ligation on cAMP
      synthesis or [3H]thymidine incorporation, there was a significant increase in
      interleukin-6 release by TFC. Thus, although TFC do not express members of the B7
      family of T cell costimulators, they do express CD40, indicating the possibility
      of mutually stimulatory T cell-TFC interaction. This has important implications,
      both for TFC synthesis of immunological mediators and for the biasing of T cell
      behavior toward a T helper 2-type phenotype.

PMID- 9543156
TI  - Measurement of leukemia inhibitory factor in biological fluids by
      radioimmunoassay.
AB  - Leukemia inhibitory factor (LIF) exhibits multiple biological activities in
      various tissues, and we have shown that LIF activates POMC gene transcription in
      response to immune signals. As higher serum levels of LIF have been reported in
      septicemia, we measured LIF values in biological fluids by RIA. Immunoreactive
      LIF was detected in 303 of 428 human serum samples. Circulating LIF detection
      rates were 69% in acute inflammatory diseases, 83% in chronic inflammatory
      diseases, 61% in noninflammatory diseases, and 90% in cancer patients. Serum
      concentrations of human LIF was higher in patients with inflammatory disease than
      in noninflammatory disease (0.80 +/- 0.10 vs. 0.53 +/- 0.02 ng/mL; P < 0.05) or
      in cancer patients (0.44 +/- 0.06; P < 0.05). Higher serum human LIF levels were
      found in septicemia (0.78 +/- 0.14 ng/mL), pneumonia (0.80 +/- 0.10 ng/mL), acute
      bronchitis (0.88 +/- 0.09 ng/mL), other infections (1.01 +/- 0.17 ng/mL), and
      systemic lupus erythematosus (SLE; 0.79 +/- 0.06 ng/mL). In 7 septicemia
      patients, Gram-negative infection was associated with higher LIF levels (1.06 +/-
      0.16 ng/mL) than was Gram-positive infection (0.58 +/- 0.14 ng/mL). In patients
      with acute inflammatory disease, serum LIF levels decreased within several days
      after hospitalization. To test circulating mouse (m) LIF changes in response to
      inflammatory stress, lipopolysaccharide (LPS) was injected ip to mice. LPS
      increased serum mLIF values concordantly with ACTH levels. After i.p. injection
      of 80 microg LPS, serum mLIF increased by 144% (P < 0.05), 173% (P < 0.05), and
      134% at 30, 90, and 120 min respectively. In vitro, however, LPS did not increase
      ACTH and mLIF secretion from dispersed mouse primary pituitary cells. These
      results suggest that LIF is an important participant in the pathogenesis of the
      acute inflammatory response. The elevated serum LIF levels observed in
      inflammation do not appear to originate from the pituitary.

PMID- 9543157
TI  - Stereological evaluation of human spermatogenesis after suppression by
      testosterone treatment: heterogeneous pattern of spermatogenic impairment.
AB  - Testosterone (T) treatment suppresses gonadotropin levels in normal men and is a
      promising reversible contraceptive that induces azoospermia in approximately 70%
      of subjects and oligospermia in the remainder; however, the basis of this
      variable response is unclear. This study aimed to investigate this reported
      variable response by examining the spermatogenic process and quantitating germ
      cell number in men after T-induced gonadotropin withdrawal. Ten normal fertile
      men (31-46 yr), already planning to undergo vasectomy, either received T
      enanthate (200 mg, i.m., weekly) for 19-24 weeks (n = 5; TE group) or proceeded
      directly to surgery (n = 5; controls), at which time a unilateral testicular
      biopsy was taken, and germ cell numbers were estimated using the optical disector
      stereological method. In response to TE treatment, serum T levels rose 2-fold,
      and FSH/LH levels became undetectable. Sperm counts fell to azoospermia in 4 men
      and to 21 million/mL in the fifth man. The mean number of type A spermatogonia
      per 100 Sertoli cells was unchanged, but type B spermatogonia fell markedly to
      10% of the control values, and later germ cell types decreased to 11-18% of the
      control values. The pattern of germ cell suppression varied widely and showed no
      relationship with sperm count or the time to azoospermia. Despite the presence of
      elongated spermatids (1.4-20% of the control), four men remained azoospermic. Two
      TE subjects with similar early germ cell complements and elongated spermatid
      numbers had sperm counts of zero and 21 million/mL; the latter man demonstrated
      marked variability in germ cell numbers between adjacent tubules. We conclude
      that 1) the principal spermatogenic lesion in TE-treated men is the marked (90%)
      inhibition of type A-->B spermatogonial maturation. Other sites are also
      affected, particularly the release and/or survival of elongated spermatids during
      transit; and 2) a steady state in germ cell number may not be established even
      after 4-5 months of TE treatment. The findings suggest that TE treatment does not
      adequately or consistently withdraw hormonal support for spermatogenesis, leading
      to variable between- and within-individual patterns of germ cell suppression.

PMID- 9543158
TI  - The follicle-stimulating hormone (FSH) threshold/window concept examined by
      different interventions with exogenous FSH during the follicular phase of the
      normal menstrual cycle: duration, rather than magnitude, of FSH increase affects
      follicle development.
AB  - According to the threshold concept, FSH concentrations need to surpass a distinct
      level to stimulate ovarian follicle growth. The window concept stresses the
      significance of a limited duration of elevated FSH levels above the threshold for
      single dominant follicle selection. The aim of this study was to investigate
      effects on follicle growth of increased FSH levels, differing in duration and
      magnitude of elevation, during the follicular phase. Twenty-three normo-ovulatory
      (cycle length, 26-31 days), young (age, 20-31 yr) women volunteered for this
      study. In all subjects a series of daily transvaginal sonography scans of the
      ovaries and blood sampling [for FSH and estradiol (E2) determinations] were
      performed during two consecutive cycles. The first study cycle (control cycle)
      started 10 days after urinary assessment of the LH surge in the preceding cycle
      (DayLH) and was concluded on the day of ovulation assessed by transvaginal
      sonography scans. The second series of daily monitoring (intervention cycle)
      started 10 days after DayLH in the control cycle. After randomization, subjects
      received either 375 IU urinary FSH, s.c., as a single injection on Day(LH+14)
      (group A; n = 11) or 75 IU daily from Day(LH+19) until Day(LH+23) (group B; n =
      12). In group A, FSH levels increased on the day after injection to a median
      concentration of 10.1 IU/L, which was 1.9 times higher (P < 0.01) than levels on
      matching days during the control cycle. Concentrations returned to basal levels 3
      days after injection. In group B, a moderate elevation of FSH concentrations (15%
      increase; P < 0.05) was observed compared to levels during the control cycle. In
      group A, E2 concentrations increased (P = 0.03) 1 day after FSH injection and
      returned to baseline levels within 2 days. In group B, E2 levels started to
      increase after the first injection of FSH and remained significantly higher (P <
      0.01) during the following 5 days compared to those on matching days in the
      control cycle. Compared to matching days in the control cycle an increased number
      of follicles 8-10 mm in size was found in group A (P < 0.01) during the period
      from Day(LH+14) until Day(LH+19), without an increase in follicles 10 mm or
      larger thereafter. In contrast, in group B, the numbers of both 8- to 10-mm and
      10-mm or larger follicles were higher during the period from Day(LH+19) until
      Day(LH+24) in group B (P = 0.02 and P < 0.01, respectively). Results from the
      present study suggest that a brief, but distinct, elevation of FSH levels above
      the threshold in the early follicular phase does not affect dominant follicle
      development, although the number of small antral follicles did increase. In
      contrast, a moderate, but continued, elevation of FSH levels during the mid to
      late follicular phase (effectively preventing decremental FSH concentrations)
      does interfere with single dominant follicle selection and induces ongoing growth
      of multiple follicles. These findings substantiate the FSH window concept and
      support the idea of enhanced sensitivity of more mature follicles for stimulation
      by FSH. These results may provide the basis for further investigation regarding
      ovulation induction treatment regimens with reduced complication rates due to
      overstimulation.

PMID- 9543159
TI  - Localization, characterization, and second messenger coupling of pituitary
      adenylate cyclase-activating polypeptide receptors in the fetal human adrenal
      gland during the second trimester of gestation.
AB  - The distribution and pharmacological properties of pituitary adenylate cyclase
      activating polypeptide (PACAP) receptors were studied in the fetal human adrenal
      gland during the second trimester of gestation. Autoradiographic studies, using
      [125I]PACAP27 as a radioligand, revealed that PACAP-binding sites are exclusively
      located on chromaffin cells of adrenals from fetuses 14-20 weeks old. Biochemical
      characterization of binding revealed the occurrence of a single class of PACAP
      binding sites with a dissociation constant value of 0.32-0.74 nmol/L and a
      binding capacity of 0.30-0.81 pmol/mg wet tissue. PACAP27 and PACAP38 were
      equipotent in competing for [125I]PACAP27 binding (IC50 = 0.28-0.64 nmol/L and
      0.15-0.81 nmol/L, respectively), and the Hill coefficients were close to 1. In
      contrast, vasoactive intestinal polypeptide was much less efficient in displacing
      the tracer (IC50 = 4-362 nmol/L), and the Hill coefficients were less than 0.6.
      PACAP38 induced a dose-dependent increase in cAMP production in fetal human
      adrenal cell suspension (ED50 = 0.07 +/- 0.02 nmol/L), as well as in cells
      maintained in culture for 5 days (5.4 +/- 1.8 nmol/L). In contrast, PACAP38
      induced a modest increase in inositol phosphate formation. These data indicate
      that type I PACAP receptors are present in the early stages of the human medulla
      organization during the process of migration of chromaffin cells from the
      periphery to the central part of the gland. The present results suggest that
      PACAP could be involved in the regulation of the human adrenochromaffin cells
      during ontogenesis.

PMID- 9543160
TI  - Evaluation of abdominal fat distribution in noninsulin-dependent diabetes
      mellitus: relationship to insulin resistance.
AB  - Accumulation of visceral adipose tissue is associated with metabolic
      complications such as noninsulin-dependent diabetes mellitus. The aim of this
      study was to evaluate the effect of abdominal adipose tissue on insulin
      sensitivity in subjects with noninsulin-dependent diabetes mellitus (NIDDM).
      Areas of abdominal fat were calculated from axial magnetic resonance images
      obtained at the level of the umbilicus in 21 men with NIDDM [age, 45.6 +/- 8.3
      (+/-SD) yr; body mass index, 29.3 +/- 4.5 kg/m(-2); total body fat (skinfold
      thickness), 26.8 +/- 5.4%; waist to hip ratio, 0.97 +/- 0.07; duration of
      diabetes, 59 +/- 47 months; hemoglobin A1c, 8.1 +/- 1.5%]. Insulin sensitivity
      was evaluated by an insulin tolerance test. The areas of deep abdominal fat and
      sc abdominal fat were, respectively, 135.3 +/- 55.1 and 211.8 +/- 99.1 cm2. The
      blood glucose disappearance rate was 2.11 +/- 0.87%/min and was negatively
      related to deep abdominal fat (r = 0.72; P = 0.0025). In contrast, areas of sc
      abdominal fat, total body fat, body mass index, and waist to hip ratio were not
      related to the blood glucose disappearance rate. Plasma triglyceride
      concentrations averaged 1.8 +/- 0.8 mmol/L and were positively related to deep
      abdominal fat (r = 0.69; P = 0.0018). We conclude that insulin sensitivity is
      strongly related to visceral adipose tissue accumulation in NIDDM.

PMID- 9543162
TI  - Human 17beta-hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid
      expression and localization in term placenta and in endometrium during the
      menstrual cycle.
AB  - According to the current hypothesis, 17beta-hydroxysteroid dehydrogenases
      (17HSDs) regulate the extent of estrogen influence in the endometrium by
      converting estradiol (E2) locally into a biologically less active sex steroid,
      estrone (E1), and vice versa. Recently, we have shown that both 17HSD type 1 and
      type 2 are expressed in the human endometrium, and in the present work, using in
      situ hybridization, we show that 17HSD type 2 is localized in the glandular
      epithelial cells as previously shown for the type 1 enzyme, but in contrast to
      type 1, the expression of type 2 is highest at the end of the cycle. Hence, we
      hypothesize that the differential expression of the two 17HSD enzymes, with
      opposite activities in same cell types, could modulate intracellular E2
      concentrations during the end of the luteal phase of the menstrual cycle. We
      further analyzed the expression of 17HSD type 1 and type 2 mRNAs in term human
      placenta. Expression of 17HSD type 1 mRNA was detected in the
      syncytiotrophoblasts, and signals for type 2 mRNA were found inside the villi,
      corresponding to cytotrophoblasts. The expression of 17HSD type 2 in the placenta
      may serve to maintain the presence of inactive sex steroids and attenuate the
      formation of biologically potent androgens and estrogens.

PMID- 9543161
TI  - The use of a sensitive equilibrium dialysis method for the measurement of free
      testosterone levels in healthy, cycling women and in human immunodeficiency virus
      infected women.
AB  - Measurements of total and free testosterone levels in women have lacked precision
      and accuracy because of limited assay sensitivity. The paucity of normative data
      on total and free testosterone levels in healthy women has confounded
      interpretation of androgen levels in women with human immunodeficiency virus
      (HIV) infection and other disease states. Therefore, the objectives of this study
      were to develop sensitive assays for the measurement of the low total and free
      testosterone levels in women to define the range for these hormones during the
      normal menstrual cycle and assess the total and free testosterone levels in HIV
      infected women. By using a larger volume of serum, increasing the incubation
      time, and reducing the antibody concentration, the sensitivity of the total
      testosterone assay was increased to 0.008 nmol/L, and that of the free
      testosterone assay was increased to 2 pmol/L. The mean percent free testosterone
      was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone
      levels in the follicular and luteal phases were not significantly different, but
      both demonstrated a modest preovulatory increase, 3 days before the LH peak.
      Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0
      ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80)
      vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower
      in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and
      free testosterone levels were also significantly lower in HIV-infected women who
      were menstruating normally. There were no significant differences in serum total
      and free testosterone levels between those who had lost weight and those who had
      not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid
      copy number. Serum FSH, but not LH, levels were significantly higher in HIV
      infected women than in controls. Using assays with sufficient sensitivity, we
      defined the range for total and free testosterone levels during the normal
      menstrual cycle. Serum total and free testosterone levels are lower in HIV
      infected women and correlate inversely with plasma HIV ribonucleic acid levels.
      The hypothesis that androgen deficiency contributes to wasting in HIV-infected
      women remains to be tested.

PMID- 9543163
TI  - Immunohistochemical localization of type 1 11beta-hydroxysteroid dehydrogenase in
      human tissues.
AB  - Two isozymes of 11beta-hydroxysteroid dehydrogenase (11betaHSD) catalyze the
      interconversion of hormonally active cortisol to inactive cortisone. Activity and
      messenger ribonucleic acid studies indicate that type 1 11betaHSD (11betaHSD1) is
      expressed in glucocorticoid target tissues such as liver, gonad, and cerebellum,
      where it regulates the exposure of cortisol to glucocorticoid receptors. To
      further understand the role of 11betaHSD1 in human tissues, we have studied the
      localization of this isozyme using an antibody raised in sheep against amino
      acids 19-33 of human 11betaHSD1. Western blot analyses indicated that the
      immunopurified antibody recognized a band of approximately 34 kDa in human liver
      and decidua. Immunoperoxidase studies on liver, adrenal, ovary, decidua, and
      adipose tissue indicated positive cytoplasmic staining for 11betaHSD1. 11BetaHSD1
      immunoreactivity was observed more intensely around the hepatic central vein,
      with no staining around the portal vein, hepatic artery, or bile ducts. No
      staining for 11betaHSD1 was observed in the adrenal medulla, but 11betaHSD1
      immunoreactive protein was observed in all three zones of the adrenal cortex,
      with the most intense staining in the zona reticularis > zona glomerulosa > zona
      fasciculata. In the human ovary, immunoreactivity was observed in the developing
      oocyte and the luteinized granulosa cells of the corpus luteum. No staining was
      observed in granulosa cells, thecal cells, or ovarian stroma, which contrasted
      with the marked expression of 11betaHSD2 in the granulosa cell layer. Sections of
      human decidua showed high expression of 11betaHSD1 in decidual cells. In omental
      adipose tissue, 11betaHSD1 immunoreactivity was observed in both stromal and
      adipocyte cells. Immunohistochemical localization of 11betaHSD1 in human liver,
      adrenal, ovary, decidua, and adipose tissue using this novel antiserum provides
      us with a tool to investigate the role of this isozyme in modulating
      glucocorticoid hormone action within these tissues.

PMID- 9543164
TI  - Fibroblast growth factors 1 and 2 and fibroblast growth factor receptor 1 are
      elevated in thyroid hyperplasia.
AB  - We have previously reported increased expression of fibroblast growth factor (FGF
      1 and FGF-2) in benign and malignant human thyroid neoplasia. To determine the
      role of these factors in thyroid hyperplasia we have examined their expression in
      multinodular goiter and compared findings with those in normal thyroid tissue.
      Because the effects of FGF-1 and FGF-2 are predominantly mediated through the FGF
      receptor-1 (FGFR-1), its expression has also been examined. Immunocytochemistry
      was performed on sections from multinodular goiters (n = 18) and normal thyroid
      (n = 7). Cytoplasmic staining for FGF-1, FGF-2, and FGFR-1 was scored on a scale
      of 0 (no staining) to 3 (heavy staining) and expressed as a percentage of total
      cells stained. Confocal microscopy of immunofluorescent staining for FGF-1, FGF
      2, and FGFR-1 in sections of multinodular goiter (n = 3) and normal thyroid (n =
      3) provided quantitation of immunostaining. FGF-1 expression was significantly
      increased in multinodular goiter when compared with normal. A mean of 74% of
      follicular cells in multinodular goiter compared with 9% of follicular cells in
      normal thyroid expressed FGF-1 (P < 0.0001). When expression of FGF-2 was
      examined, 77% of the follicular cells in multinodular goiter compared with 5% in
      normal thyroids were immunopositive (P < 0.0001). Confocal microscopy revealed
      that the intensity was 160 times greater in follicular cells in sections of
      multinodular goiters when compared with normal. When expression of FGFR-1 was
      analyzed, 89% of the follicular cells in multinodular goiter stained positively,
      compared with 15% of follicular cells in sections of normal thyroid. Confocal
      microscopy revealed a 6-fold increase in intensity of FGFR-1 expression in
      follicular cells of multinodular goiter (P < 0.05). In addition, there was
      significant nuclear expression of FGFR-1 in multinodular goiter contrasting with
      negligible expression in normal thyroid. These data show that enhanced expression
      of FGF-1, FGF-2, and FGFR-1 accompany thyroid hyperplasia and are not exclusively
      associated with the neoplastic state. These factors may be involved in the
      pathogenesis of uncontrolled thyroid growth observed in these conditions.

PMID- 9543165
TI  - Corticotropin regulates vascular endothelial growth factor expression in human
      fetal adrenal cortical cells.
AB  - The human adrenal cortex has a complex vasculature that is essential for growth,
      organ maintenance, and access of secreted hormones to the circulation. Growth and
      function of the adrenal cortex are regulated by corticotropin (ACTH), the actions
      of which are in part mediated by locally produced growth factors. As cortical
      growth and vascularization must increase in a coordinated manner, we hypothesized
      that ACTH also influences adrenal cortical angiogenesis by stimulating the local
      expression of specific angiogenic factors. Vascular endothelial growth factor
      (VEGF) is a potent endothelial cell-specific angiogenic peptide, the expression
      of which has been detected in adrenal cortical cells. Therefore, we examined the
      localization of VEGF expression in the midgestation (16-20 weeks) human fetal
      adrenal cortex and determined whether VEGF expression and secretion by isolated
      human fetal adrenal cortical cells are regulated by ACTH. By immunohistochemical
      analysis, strong cytoplasmic staining for VEGF was detected in scattered clusters
      of fetal zone (inner cortical compartment) cells. In contrast, cells in the
      outer, definitive zone of the cortex stained only weakly for VEGF. The
      predominant staining for VEGF in the fetal zone correlated with the extensive
      vasculature of this zone as detected by immunohistochemical staining for von
      Willebrand factor, which is specific for endothelial cells. In primary cultures
      of human fetal adrenal cortical cells, ACTH (1 nmol/L) and forskolin (10
      micromol/L) increased the abundance of messenger ribonucleic acid transcripts
      encoding VEGF, as assessed by Northern and slot blot analyses. The stimulatory
      effect of ACTH and forskolin on VEGF gene expression occurred within 2 h of
      agonist exposure and persisted for at least 24 h. ACTH and forskolin also
      increased VEGF protein secretion by fetal adrenal cortical cells, as assessed by
      enzyme-linked immunosorbent assay for VEGF in fetal adrenal cortical cell
      conditioned medium. A significant (P < 0.05) increase in VEGF secretion was
      detected as early as 8 h after ACTH or forskolin treatment. By 24 h after the
      addition of ACTH or forskolin, VEGF secreted from isolated human fetal adrenal
      cells was increased 5- to 6-fold. These data demonstrate that the human fetal
      adrenal cortex, particularly the cells of the inner fetal zone, express VEGF and
      that VEGF expression and secretion by these cells are directly regulated by ACTH
      and the activation of adenylate cyclase. Thus, VEGF may be a local regulator of
      adrenal cortical angiogenesis and an important mediator of the tropic action of
      ACTH, ensuring the coordination of ACTH-stimulated cortical growth and
      vascularization.

PMID- 9543166
TI  - The aromatase excess syndrome is associated with feminization of both sexes and
      autosomal dominant transmission of aberrant P450 aromatase gene transcription.
AB  - Increased extraglandular aromatization has been reported as the cause of familial
      gynecomastia. We studied a kindred with aromatase excess inherited in an
      autosomal dominant manner, in which affected males had heterosexual precocity
      and/or gynecomastia, and affected females had isosexual precocity and/or
      macromastia. The propositus was a 9-yr-old boy with gynecomastia. His 7.5-yr-old
      sister had precocious puberty, and their father and paternal grandmother had
      peripubertal gynecomastia and macromastia, respectively. Serum concentrations of
      gonadal and adrenal steroid hormones were determined before and after the
      administration of corticotropin and/or hCG. Aromatase activity was determined by
      [3H]delta4-androstenedione to [3H]estrone conversion by cultured skin fibroblasts
      and/or Epstein-Barr virus-transformed lymphocytes and was detected by
      immunohistochemistry and/or Western analysis. Linkage was examined with a
      polymorphism of the aromatase (P450arom) gene. The P450arom messenger ribonucleic
      acid was analyzed by rapid amplification of complementary DNA (cDNA) ends,
      ribonuclease protection assay, and RT-PCR. hCG testing demonstrated a high rate
      of conversion of delta4-androstenedione to estrone and of testosterone to
      estradiol in the propositus and his father. Treatment of the propositus and his
      sister was initiated with an aromatase inhibitor (testolactone) and a GnRH
      analog, which successfully delayed skeletal and pubertal development in both
      children. Markedly increased aromatase activity was found in the patients'
      fibroblasts and Epstein-Barr virus-transformed lymphocytes. The P450arom
      polymorphism segregated with the disease in the family. A new 5'-splice variant
      was present in the patients' P450arom messenger ribonucleic acid, thus
      identifying yet another first exon of this gene, which appears to be aberrantly
      expressed in this family. In conclusion, a family with the aromatase excess
      syndrome is described, in which the condition was inherited in an autosomal
      dominant manner, led to feminizing manifestations in both sexes, and was
      associated with the aberrant utilization of a novel transcript of the P450arom
      gene.

PMID- 9543167
TI  - Prostaglandin endoperoxide H synthase (PGHS) activity and PGHS-1 and -2 messenger
      ribonucleic acid abundance in human chorion throughout gestation and with preterm
      labor.
AB  - Term and preterm parturition is associated with elevated intrauterine PG
      production. Although an increase of PG synthesis by the fetal membranes during
      term labor is well documented, there is little data available regarding the
      prostanoid production of these tissues at term, before the spontaneous onset of
      labor. In the present study, we determined the expression of PG H2 synthase
      (PGHS), the committing and rate-limiting enzyme of prostanoid biosynthesis, in
      the chorion laeve during gestation. Tissues were collected from 18 patients at
      term (37-41 weeks of gestation) and from 13 patients between 17 and 35 weeks of
      pregnancy. None of the patients were in labor. PGHS-specific activity and the
      abundance of messenger RNAs (mRNAs) encoding the two PGHS isoenzymes (the
      constitutive PGHS-1 and the inducible PGHS-2) were measured by a cell-free enzyme
      assay and specific ribonuclease protection assays, respectively. PGHS-specific
      activity as well as PGHS-1 and -2 mRNA levels were significantly (P < 0.01)
      higher at term before labor than earlier during gestation. Furthermore, PGHS
      activity at term exhibited significant positive correlation with PGHS-2 mRNA
      levels, but not with PGHS-1 mRNA levels. In situ hybridization indicated that the
      expression of both PGHS mRNAs increased in the epithelial and the mesenchymal
      cells of the amnion and the chorion laeve at term. Additionally, PGHS activity
      and mRNA levels were determined in the chorion laeve of a group of patients who
      gave birth spontaneously before term (30.6 +/- 1 weeks, mean +/- SEM, n = 5), and
      the values were compared with a group who delivered by cesarean section before
      labor at a similar gestational age (31.9 +/- 1.4 weeks, n = 5, P > 0.05 vs. the
      preterm labor group). None of the patients exhibited signs of genital tract
      infection. PGHS-specific activity and PGHS-1 and -2 mRNA levels were
      significantly higher in the preterm labor group than in the group who delivered
      preterm without labor. In situ hybridization suggested that the enhanced PGHS-1
      and -2 mRNA expression occurred predominantly in the mesenchymal cells of the
      fetal membranes at preterm labor. Thus, PGHS-1 and -2 expression increases in the
      chorion laeve at term before labor, with PGHS-2 as the functionally prevalent
      isoform. This supports the possibility that PGs originating in the fetal
      membranes promote the onset of normal labor. Furthermore, preterm labor is
      associated with the elevated expression of the two PGHS isoenzymes in the chorion
      laeve. The maturation of the fetal membranes in preparation for term labor
      involves both the epithelial and the mesenchymal cells, whereas preterm labor is
      accompanied by the maturation of the mesenchymal tissue components, as reflected
      by PGHS expression. This difference may have implications in the early
      recognition of preterm labor.

PMID- 9543168
TI  - Heterogeneous dopamine D2 receptor subtype messenger ribonucleic acid expression
      in clinically nonfunctioning pituitary adenomas.
AB  - Little is known about differences in the expression, localization, and function
      of the two dopamine D2 receptor subtypes, D2short and D2long (D2s and D2l), in
      either normal or adenomatous pituitary. We investigated the messenger RNA (mRNA)
      expression of the D2 receptor (D2R) subtypes in clinically nonfunctioning
      pituitary adenomas by in situ hybridization using subtype-specific
      oligonucleotides. The five normal pituitaries studied expressed similar ratios of
      D2R subtypes mRNA with a predominant expression of the D2l isoform. In 2 of 18
      clinically inactive adenomas no D2R mRNA was found, whereas in 16 a heterogeneous
      expression of D2R isoforms was observed. Six adenomas expressed only the D2l and
      2 adenomas only the D2s subtype mRNA; the remaining 8 expressed extremely varying
      proportions of the two subtypes. The D2R was found only in a subset of the
      nonfunctioning adenoma cells. In gonadotropin-immunopositive adenomas, the D2R
      was mainly localized in LH- and FSH-immunopositive cells. Probably because of the
      heterogeneous D2R subtype expression, suppression of cell proliferation was
      observed in only 3 of 9 adenoma cell cultures in which the growth inhibitory
      effect of bromocriptine was studied. Although there is some evidence that the
      presence of the D2s receptor subtype favors the growth inhibitory response to
      bromocriptine, further studies with a larger number of inactive adenomas are
      needed to confirm this speculation.

PMID- 9543169
TI  - The human placenta and fetal membranes express the corticotropin-releasing
      hormone receptor 1alpha (CRH-1alpha) and the CRH-C variant receptor.
AB  - Placentally derived CRH plays a major role in the mechanisms controlling human
      pregnancy and parturition. It has been suggested that there is a CRH placental
      clock that is active from the early stages of pregnancy and determines the length
      of gestation and the timing of parturition. CRH can influence human reproductive
      tissue function via specific CRH receptors. Two distinct CRH receptors have been
      cloned (R1 and R2) that share 70% homology at the amino acid level and exist as
      two alternatively spliced forms (alpha and beta). In this study we investigated
      the presence of CRH receptor subtypes in human fetal membranes derived from
      spontaneous rupture and placental biopsies at term. Using RT-PCR, we identified
      the full length of the CRH-R1alpha subtype in placental and fetal membranes. In
      both tissues we also identified a spliced variant of the CRH receptor (CRH-Rc).
      We were unable to detect any CRH-R2 messenger ribonucleic acid in any of the
      biopsies. Fluorescent in situ hybridization and immunofluorescence in both
      tissues demonstrated that syncytiotrophoblast cells and amniotic epithelium are
      the major cell types expressing CRH-1alpha and CRH-Rc receptor messenger
      ribonucleic acid. Further studies are necessary to give a better insight into the
      role of CRH and its receptors in these tissues.

PMID- 9543170
TI  - Age-related changes in glucocorticoid fast feedback inhibition of
      adrenocorticotropin in man.
AB  - A decrease in hypothalamic-pituitary-adrenal axis sensitivity to glucocorticoid
      feedback suppression seems to occur with aging. To investigate possible
      abnormalities in the inhibitory effect of glucocorticoids on ACTH secretion in
      the elderly, we evaluated the endogenous ACTH response to hydrocortisone (25 mg
      as an i.v. bolus) in 15 healthy aged (65-88 yr) and 15 healthy young (18-26 yr)
      men. Blood samples for ACTH and cortisol determinations were collected at -15, 0,
      2, 5, 10, 15, 30, 45, 60, 90, 120, and 180 min. Hydrocortisone injection produced
      a rapid increase in plasma cortisol levels within the first 2 min in both groups.
      In old men, in concomitance with the cortisol increase, ACTH levels showed only a
      slight and nonsignificant decrease within the first 15 min, followed by a
      pronounced and significant decline thereafter. In young subjects, in concomitance
      with the plasma cortisol increase, a marked decrease in ACTH levels was observed
      within the first 15 min, followed by a less pronounced decline thereafter. The
      response curve of ACTH inhibition could be arbitrarily divided in two parts. The
      first part (from 0-60 min) showed a significant difference between old and young
      men, whereas the remaining part of the curve (from 60-180 min) showed no
      differences between the two groups. The slower response in glucocorticoid
      feedback inhibition of ACTH in old men supports the concept of some alteration in
      the central regulation by steroids in aging. Age-related vascular factors
      affecting cortisol penetration through the blood-brain barrier more than
      hippocampus-hypothalamus receptor abnormalities could be involved in the fast
      component of hypothalamic-pituitary-adrenal axis feedback regulation.

PMID- 9543171
TI  - Retinoid receptors expression in human term placenta: involvement of RXR alpha in
      retinoid induced-hCG secretion.
AB  - To investigate the role of retinoids on human placental development and
      functions, we characterized the spatial distribution of retinoid receptors in
      human term chorionic villi. In situ hybridization with 35S labeled sense and
      antisense probes for the RARs, alpha, beta, gamma and RXRs, alpha, beta, gamma,
      specifically detected only RAR alpha and RXR alpha. Both RAR alpha and RXR alpha
      mRNA were preferentially expressed in the trophoblast cell layer. This
      syncytiotrophoblast expression was confirmed by immunohistochemical analyses
      using anti-RAR alpha and RXR alpha antibodies. Using trophoblast cells in
      culture, we then studied the effect on hCG secretion of 0.1 microM RA
      physiological forms and of selective RAR alpha and RXR alpha synthetic agonists.
      Only RXR alpha specific ligands such as physiological 9-cis RA and synthetic Ro
      25-7386 stimulated hCG secretion (doubled). These results suggest an important
      role for RXR alpha in human placental development and function.

PMID- 9543172
TI  - Molecular characterization of the men1 tumor suppressor gene in sporadic
      pituitary tumors.
AB  - Anterior pituitary tumors arise sporadically, and also as part of the inherited
      multiple endocrine neoplasia type 1 (MEN 1) syndrome. To investigate the role of
      the recently isolated men1 gene in sporadic pituitary tumorigenesis, the complete
      coding sequence was screened for mutations in 45 sporadic anterior pituitary
      tumors, including 14 hormone-secreting tumors and 31 nonsecreting tumors, by
      dideoxy fingerprinting and sequence analysis. No pathogenic sequence changes were
      found in the men1 coding region. The men1 gene was expressed in 43 of these
      tumors with sufficient RNA, including one tumor with loss of heterozygosity (LOH)
      for several polymorphic markers on chromosomal region 11q13. Furthermore, both
      alleles were expressed in 19 tumors in which the constitutional DNA was
      heterozygous for intragenic polymorphisms. Thus, inactivation of the men1 tumor
      suppressor gene, by mutation or by imprinting, does not appear to play a
      prominent role in sporadic pituitary adenoma pathogenesis.

PMID- 9543173
TI  - Insulin and IGF binding by IGFBP-3 fragments derived from proteolysis,
      baculovirus expression and normal human urine.
AB  - Recombinant human IGFBP-3 was proteolysed with different concentrations of
      plasmin for various periods of time. The major IGFBP-3 fragment resulting from
      this digestion migrated at ca. 15 kDa in nonreducing SDS-PAGE. Following the
      identification of this fragment as an N-terminal IGFBP-3 fragment, by use of N
      terminus-specific monoclonal antibody and amino acid sequence analysis, we
      constructed and expressed a similar fragment in a baculovirus expression system.
      The fragments resulting from plasmin digestion, as well as the baculovirus
      expressed recombinant human IGFBP-3(1-97), retain weak IGF binding and show
      specific insulin binding on cross-linking and western ligand blot. RhIGFBP-3(1
      97) can inhibit insulin receptor autophosphorylation in insulin receptor
      overexpressing NIH 3T3 cells. Insulin and IGF binding to IGFBP-3 fragments could
      be further demonstrated in normal urine. These data indicate the physiological
      significance of IGFBP-3 fragments derived from proteolysis in vivo.

PMID- 9543174
TI  - Different effects of GH treatment on cognitive function in girls with Turner's
      syndrome and in adults with GH deficiency.

PMID- 9543175
TI  - Psychological stress and skydiving.

PMID- 9543176
TI  - Childhood Graves' disease--remission rate and risk factors.

PMID- 9543177
TI  - Why nobody has P450scc (20,22 desmoslase) deficiency.

PMID- 9543178
TI  - Serum leptin levels in a patient with pheochromocytoma.

PMID- 9543179
TI  - Differential expression of HGF and Met in human placenta.

PMID- 9543180
TI  - Low BMD in calcium stone formers with hypercalciuria.

PMID- 9543181
TI  - The influence of mouse housing density on autoimmune reactivity.
AB  - Splenic cells from C57BL/6 mice housed in groups (six per cage) or individually
      (one per cage) were analyzed for their ability to synthesize autoantibodies
      against autologous bromelain-treated erythrocytes. Group-housed male mice had a
      significantly lower number of autoimmune plaque forming cells (APFC) in their
      spleens than age matched female mice housed under similar conditions. However,
      when male mice were housed individually for 4 to 44 weeks, a marked increase in
      numbers of APFC were found in their spleens, approaching those of female control
      mice. Our results demonstrate that a simple environmental manipulation such as
      housing conditions can profoundly modulate autoimmune reactivity. Thus,
      alteration of the psychophysiological state determined by the quality of housing
      may significantly affect the development of autoimmune disease.

PMID- 9543182
TI  - Pancreatic IL-10 induces diabetes in NOD.B6 Idd3 Idd10 mice.
AB  - Transgenic NOD backcross mice expressing pancreatic interleukin 10 (IL-10) were
      crossed and backcrossed to NOD.B6 Idd3 Idd10 mice, which have diabetes-resistance
      alleles at Idd3 and Idd10 on chromosome 3 and have a very low frequency diabetes
      and insulitis. Insulitis and diabetes developed in almost all IL-10 transgenic
      backcross 1 (BC1) mice of the H2g(7/g7) haplotype regardless of the allelic
      status at Idd3 and Idd10. Furthermore, diabetes occurred in 23% of IL-10
      transgenic H2g(7/d) BC1 mice. These results indicate that pancreatic IL-10 is
      able to overcome the diabetes protection afforded by C57BL/6 (B6)-derived alleles
      at Idd3 and Idd10 as well as the absence of NOD MHC homozygosity, if other non
      MHC NOD-derived Idd alleles are provided.

PMID- 9543183
TI  - Serum levels of interleukins 8 and 10, interferon gamma, granulocyte-macrophage
      colony stimulating factor and soluble CD23 in patients with primary sclerosing
      cholangitis.
AB  - The presence of auto-antibodies and hypergammaglobulinaemia in patients with
      primary sclerosing cholangitis (PSC) suggest an overactive humoral immune system.
      Serum cytokines, measured using in-house double monoclonal sandwich ELISA, were
      used to assess the state of cellular and humoral immunity in this condition by
      comparison with sex and age matched normal controls and patients with alcoholic
      cirrhosis (AC). Soluble CD23 (sCD23) as a marker of humoral immunity was
      significantly elevated in PSC (N = 31) relative to patients with AC (N = 12) and
      the control group (N = 20) (P < 0.0001 and P < 0.001 respectively). Serum
      interleukin (IL) 10, as an anti-inflammatory cytokine and IL8, as a marker of
      neutrophil activation were significantly elevated in patients with PSC relative
      to those with AC and the controls (P < 0.001 and P < 0.05 respectively).
      Interferon gamma, as a marker of cellular immunity, and granulocyte-macrophage
      colony stimulating factor, a marker of monocyte/macrophage function were similar
      in all the groups. Cytokines and sCD23 were no different between patients with AC
      and the control group. While more than two thirds of the patients with PSC were
      positive for ANCA, there was no correlation between the presence of ANCA or ANCA
      titre and serum levels of either IL8, IL10 and sCD23. These results suggest
      exaggerated humoral immunity in PSC. The raised levels of IL10 and IL8 in PSC are
      discussed in the context of inflammatory bowel disease and liver dysfunction.

PMID- 9543185
TI  - Cytokines and autoimmune beta cell destruction in NOD mouse fetal pancreas
      isografts in cyclophosphamide-induced diabetes.
AB  - The role of cytokines in a model of cyclophosphamide (CP)-accelerated beta cell
      destruction in fetal pancreas isografts transplanted into NOD mice was studied.
      One group of prediabetic NOD mice was injected with CP at a dose of 300 mg/kg
      i.p. and 7 days later isografts of organ cultured fetal pancreas (FP) were
      transplanted under the kidney capsule of these and untreated control mice. The
      mice were killed at several time points post-transplantation and the histological
      appearance of the host pancreas used to evaluate the disease progress in the
      grafts since previous studies had shown good correlation between isograft and
      native pancreas pathology. Intragraft cytokine gene expression was monitored by
      reverse-transcriptase polymerase chain reaction (RT-PCR) at the same time points
      and the expression levels between the experimental groups compared to normal
      kidney tissue. In comparison to isografts from non-CP injected mice, isografts
      from CP-treated mice showed increased expression of IFN-gamma, TNF-alpha, TNF
      beta, IL-5, and eotaxin but no increase in IL-10 expression. The enhanced
      transcription of these cytokines correlated with massive infiltration of immune
      cells and ongoing beta cell destruction in the host pancreas of the CP-treated
      recipients.

PMID- 9543184
TI  - Anti-laminin reactivity and glomerular immune deposition by in vitro recombinant
      antibodies.
AB  - Growing evidence suggests that recombinatorial events prior to antigen contact
      can generate pathogenic autoantibodies in the nonautoimmune individual, thus
      providing potential disease mediators if conditions arise that permit bypass of
      tolerance and activation of autoreactive lymphocytes. To examine the disease
      potential of selected germline antibody genes, Ig were created de novo by in
      vitro recombination of Ig H and L chains. H chain loss variant (i.e., L-chain
      only) cell lines were transfected with a DNA construct encoding the variable
      region and regulatory sequences (LamH) of a nephrotropic murine lupus anti
      laminin Ig, and the resultant Ig were examined for in vitro antigen reactivity
      and in vivo glomerular immune deposition. The results indicate that two light
      chains, LamL (Vk8, Jk5) and 238L (Vk4, Jk5), expressing unrelated germline V1
      genes, combine with LamH to generate Ig that bind basement membrane laminin in
      vitro, diverge in their capacity to bind ssDNA, and produce two distinct patterns
      of glomerular immune deposits in vivo: dense mesangial matrix (LamH/LamL) and
      dramatic linear glomerular basement membrane (LamH/238L) deposits. The Ig genes
      used by both LamH and 238L are present in nonautoimmune mice as well as in lupus
      prone strains. We conclude that certain unmutated Ig genes can contribute to
      multiple distinct disease associated specificities, including binding to
      intrinsic kidney antigens, and that mutation is not essential to generate these
      Ig. Collectively, these observations suggest that pathogenic autoantibodies can
      be generated in the normal preimmune repertoire by random recombinatorial and
      somatic events in the absence of mutation.

PMID- 9543186
TI  - Autoantibody binding to steroid 21-hydroxylase--effect of five mutations.
AB  - Steroid 21-hydroxylase (21-OH) is a key haem containing steroidogenic enzyme and
      a major adrenal specific autoantigen. Cys 428 in 21-OH is thought to have an
      important role in haem binding and we now describe the effects of mutations at
      Cys 428 (to Ser, Arg and Phe) on 21-OH autoantibody binding. Expression of wild
      type and mutated 21-OH was carried out using an in vitro
      transcription/translation (TnT) system and reactivity of 21-OH autoantibodies
      with mutated 21-OH analysed by western blotting (in the case of unlabelled
      proteins) or immunoprecipitation assay (IPA) (in the case of 35S-labelled
      proteins). All 3 substitutions at Cys 428 had similar effects on 21-OH
      autoantibody binding and each one caused a reduction in autoantibody binding to
      about 50% of wild type in the case of IPA and to about 70% of wild type in the
      case of western blotting analysis. In addition to mutations at Cys 428, we
      studied 2 naturally occurring mutations at Pro 30 to Leu and Ile 172 to Asn which
      are associated with diminished 21-OH enzyme activity. The Pro 30 mutation had no
      effect, but the Ile 172 mutation caused a reduction in 21-OH autoantibody binding
      in the IPA to about 80% of wild type. Overall, our studies emphasise the close
      relationship between the 21-OH aminoacid sequences important for 21-OH enzyme
      activity and 21-OH autoantibody binding.

PMID- 9543187
TI  - Glutamate decarboxylase antibodies in non-diabetic pregnancy precedes insulin
      dependent diabetes in the mother but not necessarily in the offspring.
AB  - We studied the risk for diabetes of glutamate decarboxylase (GAD65Ab) and islet
      cell (ICA) autoantibodies in non-diabetic pregnant mothers and their children.
      Pregnancy and cord blood sera were collected in 1970-87 from about 35,000 mothers
      who delivered a child in the city of Malmo, Sweden. A total of 42 mothers were
      identified in 1988 who, 1-18 years after their pregnancies, had developed either
      insulin-dependent (n = 22) or non-insulin dependent (n = 20) diabetes mellitus.
      First, in 123 pregnant mothers selected as controls, 0.8% had GAD65Ab and 0.8%
      ICA. Second, among the mothers with non-insulin dependent diabetes, 7/20 (35%)
      had GAD65Ab eight months to 13 years, 10 months before clinical diagnosis. Third,
      in mothers who later developed insulin-dependent diabetes, 12/22 (55%) had
      GAD65Ab and 10/22 (45%) had ICA in pregnancies preceding the clinical diagnosis
      by 13 months to 9 years, 4 months. In 1996, none of the children born to the 42
      mothers have developed diabetes. GAD65Ab and ICA in non-diabetic pregnancies may
      predict insulin-dependent diabetes in the mother but not necessarily in the
      offspring.

PMID- 9543188
TI  - The relationship of health beliefs and psychological mood to patient adherence to
      oral hygiene behaviour.
AB  - Patient adherence to oral hygiene instructions (compliance) is important for the
      success of periodontal treatment. However, there are many different definitions
      and measures of what constitute patient adherence. Also, many different models of
      patient behaviour have been studied, with inconsistent or conflicting findings.
      The purpose of this study was to explore the relationships between health beliefs
      (three aspects of dental health locus of control, health values and adherence
      intent), psychological mood and periodontal outcomes. Complete periodontal data
      were obtained for 47 untreated patients prior to instruction in oral hygiene, and
      again 4-6 weeks later. Psychological variables were measured by questionnaire and
      adherence was measured by reductions in clinical variables (plaque and
      inflammation). Data were analysed using an item analysis of the questionnaire to
      assess the internal consistency of the subscales. The results showed overall
      stability in the psychological variables and reductions in the clinical
      variables. The main result was a series of negative associations between plaque
      scores and adherence intent. Inflammatory variables showed some association with
      psychological constructs related to dependence on external factors.

PMID- 9543189
TI  - Influence of smoking on the outcome of periodontal surgery. A 5-year follow-up.
AB  - The 5-year outcome following periodontal surgery was evaluated in 57 patients
      that had received regular maintenance care throughout the follow-up period. The
      study population included 20 smokers, 20 former smokers and 17 non-smokers in the
      age range 37-77 years. The clinical characteristics evaluated were supragingival
      plaque, gingival bleeding and pocket probing depth. The region assigned for
      surgery was, in addition, radiographically evaluated in terms of periodontal bone
      height. Furthermore, the occurrence of the periopathogens Actinobacillus
      actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Prevotella
      intermedia (Pi) and the gingival crevicular fluid (GCF) levels of tumor necrosis
      factor alpha (TNF-alpha) were assessed at follow-up. Plaque index was 28.5% at
      baseline and 32.9% at follow-up, indicating a good standard of oral hygiene, and
      gingival bleeding 31.7% and 24.9%, respectively, suggesting a low to moderate
      level of gingival inflammation. In regions assigned for surgery, pocket probing
      depth decreased significantly from on average 5.6 mm to 4.3 mm (p<0.0001) and
      periodontal bone height increased significantly from on average 62.5% to 67.5%
      (p<0.0001). In terms of bone height, the outcome was less favorable among smokers
      compared with non-smokers. There was a predominance of smokers among patients
      exhibiting loss of bone height after the 5 years of maintenance. No significant
      associations were found between the therapeutical outcome and supragingival
      plaque or subgingival occurrence of periopathogens. The associations between GCF
      levels of TNF-alpha and probing depth and bone height were unclear, whereas the
      level of TNF-alpha was significantly elevated in smokers.

PMID- 9543190
TI  - The effectiveness of different root debridement modalities in open flap surgery.
AB  - It is unclear what degree of roughness or smoothness result from use of hand
      instruments alone in comparison to the use of hand instruments in combination
      with other aids and how it may effect the grade of cleanliness. The aim of this
      study was to determine in vivo whether the combination of hand instruments with
      other aids can increase the effectiveness of root debridement. 11 patients with
      holpless 4 mandibular incisors were involved in this study. After elevating a
      lingual and buccal mucoperiosteal flap, the 4 incisors were randomly treated with
      either: (1) no treatment (control); (2) 5-min scaling (method 1); (3) 4-min
      scaling and 1 min instrumentation with a perio-diamond bur (15 microm) (method
      2); (4) 3-min scaling, 1-min instrumentation with a perio-diamond bur (15 microm)
      and 1 min with an air abrasive system (method 3). The cleanliness of the surface
      was determined using the method of Eschler and -Rapley. The degree of roughness
      (Ra and Rt) were measured with a laser beam (computer supported optical surface
      sensor system). In addition, an SEM analysis was performed. With regard to the
      remaining calculus (surface cleanliness), method 3 yielded significantly better
      results than the other 2 methods. The roughness analyses also exhibited that
      method 3 is superior to methods 1 and 2. The qualitative results of the SEM
      investigations demonstrated the most homogeneous and smooth surfaces with method
      3. Root debridement in vivo was most significant using a combination of different
      treatment modalities (i. e., curettes, perio-diamond bur and air abrasive
      system).

PMID- 9543191
TI  - Long-term effects of root-resective therapy in furcation-involved molars. A 10
      year longitudinal study.
AB  - The present investigation was designed to evaluate the long-term effect of root
      resective therapy in the treatment of furcation-involved molars. The patient
      sample included 72 patients, 21-62 years of age, who presented periodontal
      lesions in the posteriors segments of the mouth including furcation involvement
      of various degrees. After an initial examination, each patient was subjected to a
      series of full-mouth scaling and root planing. They were recalled 1-3 months
      later for a presurgical examination and subsequently underwent the corrective
      phase of therapy. During the surgical procedure, the furcation-involved teeth
      were subjected to root-resective therapy in conjunction with osseous recontouring
      and apically positioned flaps (test sites). A surgical procedure identical to the
      test procedure was performed in the non-furcation-involved teeth (control sites)
      with the exception of the root resection. At the completion of the active phase
      of treatment, 175 test and 175 control sites were available for the study. After
      a period of 6 months of healing and plaque control supervision following surgical
      procedures, the patients were recalled for a baseline examination. They were then
      enrolled in a maintenance program including professional tooth cleaning every 26
      months. The patients were re-examined 3, 5 and 10 years post-operatively. The
      results of the assessments demonstrated that the survival rate, during the 10
      year period of observation, reached 93% at test and 99% at control sites. The
      positive treatment outcome at the root-resected, furcation-involved teeth as well
      as at non-furcation-involved teeth was probably the consequence of the
      reestablishment of a tissue morphology favorable for oral hygiene and careful
      plaque control by the patients.

PMID- 9543192
TI  - Untreated periodontal disease in Indonesian adolescents. Clinical and
      microbiological baseline data.
AB  - At present, several risk factors for the initiation and progression of
      periodontitis have been identified. In order to investigate the role of various
      potential clinical and microbiological risk factors and indicators, a
      longitudinal study was initiated in a young population deprived from regular
      dental care. The present communication describes the baseline cross-sectional
      data obtained in 1987 in terms of the clinical periodontal condition and
      prevalence of periodontal bacteria in the oral cavity. All inhabitants in the age
      range 15-25 years of a village with approximately 2000 inhabitants at a tea
      estate on Western Java, Indonesia, were examined clinically and
      microbiologically. In total, 255 adolescents, comprising 130 males and 125
      females participated in the study. Samples for bacteriological examination were
      taken from the gingiva, the dorsum of the tongue, and the saliva. Plaque index,
      bleeding upon probing, pocket depth, and attachment loss (AL) were scored on the
      approximal surfaces from the vestibular aspect of all teeth as well as the mid
      vestibular and mid-lingual aspects of the Ramfjord teeth. Calculus was scored
      only on the 4 surfaces of the Ramfjord teeth. Following the clinical
      measurements, the deepest bleeding pocket with no clinical loss of attachment was
      sampled for microbiological examination. In addition, in 37 subjects a deep
      bleeding (> or = 4 mm) with at least 4 mm of attachment loss was sampled.
      Moderate periodontitis (max. AL 3-4 mm) was found in 26% of the population,
      advanced periodontitis (max. AL > or = 5 mm) in 8%, whereas 66% of the population
      showed no or minor periodontitis (max. AL 0-2 mm). Actinobacillus
      actinomycetemcomitans was found in 57% of the population, Porphyromonas
      gingivalis in 87%, Prevotella intermedia and motile rods in all cases and
      spirochetes in 89%. P. gingivalis (66%), A. actinomycetemcomitans (37%) and
      spirochetes (63%) were, of all the sampled sites of the oral cavity, most
      frequently detected in pockets without attachment loss. Motile rods were most
      prevalent on the tongue and in the saliva (92% and 89%, respectively). A high
      prevalence of the investigated periodontal bacteria was detected both in the
      pockets without and with attachment loss. No significant association between the
      clinical periodontal parameters and the prevalence of the microorganisms was
      observed at a patient level. At a site level, both P. gingivalis and spirochetes
      were more prevalent in sites with attachment loss. The actual role of these
      putative periodontal pathogens may be elucidated more extensively, when
      longitudinal data on the present population become available.

PMID- 9543193
TI  - Pre-transplant gingival hyperplasia predicts severe cyclosporin-induced gingival
      overgrowth in renal transplant patients.
AB  - The relationship between the pre-transplant periodontal status and the
      development of post-transplant gingival overgrowth was investigated in a
      longitudinal study. The periodontal condition of 35 patients was examined on 2
      occasions while they were on the transplant waiting list and then at 4-6, 10-12,
      16 and 20 weeks post-transplant. At each visit the plaque index, the bleeding
      index and a pocket index (CPITN) were measured. Dental impressions were taken of
      the pre- and post-transplant gingival condition and used to make stone models
      which were used to score the gingival overgrowth index (GOI). The patients
      divided into 3 distinct groups having severe (n=13), mild (n=16) or no post
      transplant gingival overgrowth (n=6). Only 1 of the patients had taken
      cyclosporin prior to inclusion into the study. All the patients who developed
      severe overgrowth had evidence of gingival hyperplasia before the transplant.
      There was no difference in the serum cyclosporin levels between the three groups
      (chi2<2.28, p>0.319). Furthermore, there was no statistical difference for any of
      the periodontal indices. This study indicates that the hyperplastic gingival
      inflammatory response of some individuals appears to be potentiated by
      cyclosporin resulting in severe post-transplant overgrowth. In other patients the
      same reaction may allow the fibroblastic activity to occur to an extent where it
      produces a mild clinically apparent overgrowth.

PMID- 9543194
TI  - Gingival inflammation and subgingival calculus as determinants of disease
      progression in early-onset periodontitis.
AB  - This study was undertaken to test the hypothesis that gingival inflammation and
      dental calculus are important determinants of the development and progression of
      early-onset periodontitis. The study sample included 156 individuals who were 13
      20 years old at baseline and who were examined 2x during 6 years to assess the
      attachment loss, gingival state and the presence of dental calculus. 33 (21%), 62
      (40%), and 61 (39%) individuals were classified as having localized, generalized,
      or incidental EOP, respectively. The results showed an increase in the % of teeth
      with overt gingivitis and subgingival calculus, and also an increase in the % of
      teeth showing attachment loss during the 6-year period in all classification
      groups. Of teeth with 0-2 mm attachment loss at the beginning of the study and
      which developed > or = 3 mm attachment loss during the following 6 years, there
      were 2x as many teeth with overt gingival inflammation, and 4x more teeth with
      subgingival calculus at baseline than teeth without. Gingivitis and subgingival
      calculus when present at both examinations resulted in a stronger association
      with the development of new lesions than presence of these variables at baseline.
      Teeth with gingivitis at baseline had a significantly higher mean attachment loss
      during 6 years than teeth without gingivitis (p<0.0001), and teeth with
      subgingival calculus at baseline had a significantly higher mean attachment loss
      than teeth without subgingival calculus (p<0.0001). The presence of gingivitis
      and subgingival calculus at baseline and 6 years later was associated with the
      occurrence of even higher disease progression during this period. The association
      between gingival inflammation and subgingival calculus and the development and
      progression of attachment loss during the study period in the generalized and the
      localized EOP groups was significantly higher than the association in the
      incidental EOP group. In an appreciable % of the sites in all 3 groups, however,
      the presence of the 2 factors was not associated with attachment loss during 6
      years. The results suggest a significant association between gingival
      inflammation and subgingival calculus and the development and progression of
      early-onset periodontitis.

PMID- 9543195
TI  - Nicotine and smokeless tobacco effects on gingival and peripheral blood
      mononuclear cells.
AB  - The pathogenesis of tobacco-related periodontal diseases is not well understood.
      The purpose of this study was therefore to investigate smokeless tobacco extract
      (ST) and nicotine effects on prostaglandin E2 (PGE2) and interleukin-1beta (IL
      1beta) secretion by peripheral blood mononuclear cells (PBMC, consisting of
      monocytes and lymphocytes) and gingival mononuclear cells (GMC). Both peripheral
      blood and gingival tissue adjacent to the alveolar crest were taken from non
      smoking adult periodontitis patients. Gingival tissue was treated with
      collagenase and deoxyribonuclease and GMC and PBMC were isolated by Ficoll
      Hypaque centrifugation. GMC and PBMC (100,000 cells/200 microl) were cultured for
      24 hours in supplemented RPMI 1640 alone (control), or in supplemented RPMI 1640
      containing 1% ST, 100 microg/ml nicotine, 1 microg/ml Porphyromonas gingivalis
      LPS, or 1 microg/ml P. gingivalis LPS and either 100 microg/ml nicotine or 1% ST.
      Enzyme immunoassays were used to quantify PGE2 and IL-1beta. Treatments were
      compared by repeated measures ANOVA. 100 microg/ml nicotine (7-fold, p<0.02) and
      1% ST (3.5-fold, p<0.004) significantly increased secretion of PGE2 by PBMC
      relative to control cultures. 100 microg/ml nicotine and 1% ST, however, had no
      effect on IL-1beta secretion by PBMC. Enhanced PGE2 secretion also was seen when
      PBMC were treated with P. gingivalis LPS+ 100 microg/ml nicotine relative to P.
      gingivalis LPS alone (p<0.007). In contrast, 100 microg/ml nicotine significantly
      downregulated IL-1beta secretion by GMC relative to medium alone (p<0.008) and
      had no effect on PGE2 secretion by GMC. These data indicate that while nicotine
      and ST can stimulate PBMC to secrete PGE2, they cannot activate further
      mononuclear cells extracted from gingiva, possibly due to maximal previous
      stimulation in the periodontitis lesion.

PMID- 9543196
TI  - GTR treatment of degree III furcation defects with 2 different resorbable
      barriers. An experimental study in dogs.
AB  - The aim of the present study was to describe the periodontal tissue that formed
      after GTR when different resorbable barriers were applied to degree III furcation
      defects. The study was performed in 5 foxhound dogs. The 2nd and 4th premolars in
      both sides of the mandible were extracted. Degree III furcation defects were
      produced in the 3rd mandibular premolars. 5 weeks later, GTR therapy using a
      barrier composed by a polylactide-glycolide copolymer was performed on one
      quadrant (group A). In the contralateral quadrant, a barrier made of polylactide
      and citric acid ester (group B) was used. The dogs were sacrificed 6 months after
      reconstructive therapy. Tissue blocks containing the experimental teeth were
      excised, demineralised in EDTA and embedded in paraffin. Serial sections were cut
      in the mesio-distal plane and parallel with the long axis of the roots. The
      microtome was set at 7 microm. The sections were stained in hematoxyline and
      eosin. From each biopsy, 3 sections representing the central part of the
      furcation were selected for light microscopic examination. In the healed
      furcation sites, descriptive histological analysis and histomorphometric
      measurements of the newly formed tissues were performed. In both groups the root
      surface of the healed furcation defects was covered by a cellular, extrinsic
      intrinsic fibers type cementum. The composition of the newly formed periodontal
      ligament was similar in both groups. The proportions of bone, bone marrow and
      periodontal ligament, however, were substantially larger in group A than in group
      B. In Group B, an area in the previous furcation defect was consistently occupied
      by a granuloma. It is suggested that the presence of the granuloma in the healed
      furcation defect prevented bone regrowth.

PMID- 9543197
TI  - Gingival ulceration in HIV infection. A case series and case control study.
AB  - All cases of HIV-associated gingival ulceration seen at a dedicated dental clinic
      in a 5-year period were reviewed and compared against other patients attending
      the clinic. 94 (7.1%) of 1308 patients had 146 episodes of gingival ulceration.
      89 patients had 140 episodes similar to acute necrotising ulcerative gingivitis
      (ANUG) and responded well to conventional treatment for ANUG. The cases were
      compared with 269 controls in logistic regression. Gingival ulceration was
      associated with oral candidiasis, lower age and lack of AIDS diagnosis possibly
      due to a protective effect of co-trimoxazole medication. 5 patients with
      neutropenia had extensive ulceration without the microflora of ANUG.
      Histopathology, viral and bacterial culture revealed non-specific changes. The
      ulcers did not respond to the treatment regimen for ANUG but responded to
      treatment of their neutropenia. Gingival ulceration is not common in HIV
      infection. Most cases resemble severe ANUG. It is more frequent in younger
      people, those with oral candidiasis and without AIDS. Co-trimoxazole may be
      protective. A minority of cases with ulceration and associated neutropenia
      resembled the non-specific oral ulceration associated with HIV.

PMID- 9543198
TI  - Clozapine in bipolar disorder: treatment implications for other atypical
      antipsychotics.
AB  - Traditional neuroleptics are often utilized clinically for the management of
      bipolar disorder. Although effective as antimanic agents, their mood stabilizing
      properties are less clear. Additionally, their acute clinical side effect profile
      and long term risk of tardive dyskinesia, particularly in mood disorder patients,
      portend significant liability. This review focuses on the use of atypical
      antipsychotics in the treatment of bipolar disorder focusing on clozapine as the
      prototypical agent. Although, preclinical research and clinical experience
      suggest that the atypical antipsychotics are distinctly different from typical
      antipsychotics, they themselves are heterogeneous in profiles of
      neuropharmacology, clinical efficacy, and tolerability. The early clinical
      experience of clozapine as a potential mood stabilizer suggests greater antimanic
      than antidepressant properties. Conversely, very preliminary clinical experience
      with risperidone suggests greater antidepressant than antimanic properties and
      some liability for triggering or exacerbating mania. Olanzapine and sertindole
      are under investigation in psychotic mood disorders. The foregoing agents and
      future drugs with atypical neuroleptic properties should come to play an
      increasingly important role, compared to the older classical neuroleptics, in the
      acute and long term management of bipolar disorder.

PMID- 9543199
TI  - Auditory event related potentials in major depression: prolonged P300 latency and
      increased P200 amplitude.
AB  - BACKGROUND: Some studies have shown disturbances in auditory event related
      potentials (AERPs) in patients with major depression. METHODS: In this
      exploratory study, the late AERP components, N100 (latency), P200 (amplitude and
      latency) and P300 (amplitude and latency) were recorded in 68 subjects, i.e. 39
      major depressed subjects, with (n=4) or without (n=35) cognitive deterioration,
      18 patients with Alzheimer's dementia (SDAT) and 11 normal volunteers. Twenty
      five major depressed patients had repeated measurements of AERPs both before and
      after treatment with antidepressants. RESULTS: Major depressed subjects without
      cognitive deterioration had significantly higher P300 latency and P200 amplitude
      than normal volunteers. SDAT patients and major depressed patients with cognitive
      impairment had a significantly higher P300 latency than depressed patients
      without cognitive impairment. In the latter, no significant alterations in any of
      the AERP components upon subchronic treatment with antidepressants were recorded.
      Nonresponders to antidepressant therapy had significantly higher pretreatment
      P300 latency and P200 amplitude than responders to treatment (P=0.006) and normal
      volunteers (P=0.0004). CONCLUSIONS: The findings may suggest that delayed P300
      latency as well as increased P200 amplitude accompany major depression and may
      predict a nonresponse to subsequent antidepressive therapy.

PMID- 9543200
TI  - Increased heart rate in depressed subjects in spite of unchanged autonomic
      balance?
AB  - A clinical study was conducted to examine the effects of depression on cardiac
      autonomic control. Cardiac autonomic control was measured in 26 nonmedicated
      patients (19 females) suffering from Major Depression, melancholic type, and in
      26 age- and sex-matched normal controls. We measured heart rate and high
      frequency heart rate variability (respiratory sinus arrhythmia), pulsewave
      velocity and blood pressure, during 10 min of supine rest under controlled
      conditions. Using a log transformed time domain measure of respiratory sinus
      arrhythmia (logRSA), we found an inverse linear dependence between cardiac vagal
      tone and age in the healthy subjects as well as the depressed patients. logRSA
      was 0.22+/-0.25 in the patients and 0.25+/-0.16 in the control group. While this
      difference was not significant (P > 0.1), the deviations from the regression line
      were significantly (P < 0.0005) greater in the patients (0.21+/-0.12) than in the
      control group (0.09+/-0.07), indicating a more heterogeneous vagal tone in the
      depressed patients. Heart rate was also significantly (P < 0.03) greater in the
      depressed patients (76.6+/-12.4) than in the control group (69.5+/-6.9). No
      between-group differences were found in pulsewave velocity or systolic blood
      pressure, but diastolic blood pressure was lower in depressed patients (73.5+/
      8.7 vs. 80.8+/-9.1). We discuss the possibility that the increased heart rate
      seen in the absence of vagal tone changes may not be due to altered vagal or
      sympathetic tone, as measured in this study. Other factors, including altered
      autonomous heart rate, may be responsible for the higher heart rate in the
      depressed group.

PMID- 9543201
TI  - Choosing an antidepressant: effectiveness based pharmacoeconomics.
AB  - BACKGROUND: SSRIs have been one of the major innovations in psychopharmacology in
      recent years. The debate over the competing claims of SSRIs and the older,
      cheaper TCAs has implications for clinical practice and prescribing expenditure.
      Several reviewers have focused on acquisition costs and stressed the higher costs
      associated with using SSRIs. METHODS: Recently there have been several
      applications of economics to the issue of whether to use SSRIs or TCAs as first
      line antidepressants. Most have argued that there is an economic case for using
      SSRIs. Several previous papers have used modelling techniques and decision
      analysis to generate economic evaluations from clinical trials. This paper
      examines some recent studies based on retrospective evaluations of real patients
      and real practices. Their methods and results are summarised and discussed.
      RESULTS: They all suggest that in practice, where concerns are with effectiveness
      rather than efficacy, there are advantages to be gained from using SSRIs.
      CONCLUSIONS: There are important questions about how to perform such economic
      evaluations. Clinical practice has long viewed the RCT as a 'gold standard' for
      evaluation. Some SSRI/TCA comparisons, incorporating economic studies, are under
      way and will be reported on eventually. When they appear, these studies should be
      examined carefully for their implications for antidepressant prescribing.

PMID- 9543202
TI  - A functional variant of the serotonin transporter gene in families with bipolar
      affective disorder.
AB  - BACKGROUND: The serotonin transporter protein (SERT) reuptakes serotonin from
      synapses and has been implied as the site of therapeutic action of many
      antidepressant drugs. SERT is one of the most relevant candidate genes for
      bipolar affective disorder. Recently a functionally important 44 basepair
      deletion in the regulatory region of the SERT gene was described. Association
      between this variant and affective disorder has been suggested. METHODS: The
      present study analysed this variation and another variation in the SERT gene and
      nearby DNA markers in order to test for linkage between SERT and bipolar
      affective disorder in two Danish families. RESULTS AND CONCLUSION: There was no
      evidence that variants in the SERT gene were a stronger dominant disease gene for
      the development of affective disorder in the families. The possibility of a
      recessive disease gene at or near SERT could not be excluded. LIMITATIONS: The
      present study cannot exclude if variations at or near the SERT gene were weak
      susceptibility genes or determine if they are important for other characteristics
      than presence or absence of disease. CLINICAL RELEVANCE: Further studies of the
      SERT gene in affective and other disorders, as well as in relation to treatment
      response to antidepressants are needed.

PMID- 9543203
TI  - Seasonal Affective Disorder and response to light in two patients with learning
      disability.
AB  - BACKGROUND: Seasonal Affective Disorder is now a well recognised variant of
      recurrent depressive disorder. No previous description of its occurrence in
      people with a learning disability has appeared. METHODS: Two patients are
      described who manifested seasonal cycles in mood related behaviour. RESULTS: Both
      patients were treated with bright artificial light and showed adequate clinical
      responses. CONCLUSION: Patients with a learning disability and recurrent
      behavioural changes indicative of a mood disorder should be assessed for the
      seasonal pattern of the illness and, if appropriate, given a trial of treatment
      with bright artificial light. LIMITATION: The data relates to two case reports
      without structured assessments. Further studies in this population should use
      standardised diagnostic criteria and systematic severity of depression scores.
      CLINICAL RELEVANCE: Patients with poor verbal skills may not be able to express
      their seasonal changes adequately but careful observation of the timing of
      behavioural abnormalities may aid the diagnosis of SAD leading to new therapeutic
      possibilities in phototherapy.

PMID- 9543204
TI  - Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell
      membranes of depressed patients.
AB  - BACKGROUND: There is a hypothesis that lack of n-3 polyunsaturated fatty acids
      (PUFAs) is of aetiological importance in depression. Docosahexaenoic acid, a
      member of the n-3 PUFA family, is a crucial component of synaptic cell membranes.
      The aim of this study was to measure RBC membrane fatty acids in a group of
      depressed patients relative to a well matched healthy control group. METHOD: Red
      blood cell (RBC) membrane levels, and dietary PUFA intake were measured in 10
      depressed patients and 14 matched healthy control subjects. RESULTS: There was a
      significant depletion of RBC membrane n-3 PUFAs in the depressed subjects which
      was not due to reduced calorie intake. Severity of depression correlated
      negatively with RBC membrane levels and with dietary intake of n-3 PUFAs.
      CONCLUSION: Lower RBC membrane n-3 PUFAs are associated with the severity of
      depression. LIMITATIONS: Although patient numbers were small, confounding factors
      were well controlled for and the results were highly significant. Results of the
      dietary data would tend to be weakened due to the limitations associated with
      dietary assessment. CLINICAL RELEVANCE: The findings raise the possibility that
      depressive symptoms may be alleviated by n-3 PUFA supplementation.

PMID- 9543205
TI  - Testosterone replacement therapy for hypogonadal men with SSRI-refractory
      depression.
AB  - BACKGROUND: Testosterone replacement therapy is an effective treatment of some
      depressive symptoms in hypogonadal men, and may be an effective augmentation
      treatment for SSRI-refractory major depression in such men. METHODS: We treated
      five depressed men who had low testosterone levels and had not responded to an
      adequate SSRI trial with 400 mg testosterone replacement biweekly for 8 weeks.
      Four patients underwent single-blind placebo discontinuation. Patients were
      assessed at baseline and biweekly thereafter using the Hamilton Depression Rating
      Scale (HAM-D) and the Endicott Quality of Life Enjoyment and Satisfaction Scale
      (Q-LES-Q). RESULTS: Patients' mean age was 40 years, and mean testosterone level
      277 ng/dl. All had a rapid and dramatic recovery from major depression following
      testosterone augmentation: mean 21-item HAM-D decreased from 19.2 to 7.2 by week
      2, and to 4.0 by week 8; mean Q-LES-Q increased from 45% to 68%. Three of four
      subjects who underwent discontinuation of testosterone under single-blind placebo
      treatment began to relapse. CONCLUSION: Testosterone replacement therapy may be
      an effective treatment of depressive symptoms in some men, and warrants further
      research.

PMID- 9543206
TI  - Negative symptoms, depression, and parkinsonian symptoms in chronic, hospitalised
      schizophrenic patients.
AB  - BACKGROUND: Negative symptoms of schizophrenia are often confounded by
      overlapping depressive and parkinsonian symptoms. The role of medication as an
      aetiological factor in the development of these symptoms is an important issue
      for prevention and treatment. METHODS: A total of 45 inpatients in chronic wards
      who met RDC criteria for schizophrenia were assessed with the Hamilton depression
      rating scale (HDRS) and negative symptom rating scale (NSRS) and the targeting
      abnormal kinetic effect scale (TAKE). RESULTS: No significant correlation was
      found between the total scores on the vegetative superfactor of the HDRS and the
      NSRS. Duration of neuroleptic treatment was positively correlated with depressive
      symptoms (r=0.299, P < 0.05) and negative symptoms (r=0.443, P < 0.001). Dose of
      antipsychotic was also correlated positively with negative symptoms (r=0.260, P <
      0.05). Age was negatively correlated with depressive symptoms as assessed by the
      HDRS (r=0.306, P <0.05). CONCLUSION: The data suggest that depressive and
      negative symptoms can be separated in chronic schizophrenia, while pointing to a
      possible role of antipsychotic medication in the aetiology. LIMITATIONS: The
      study was conducted in a small chronically hospitalised population treated with
      relatively high doses of antipsychotics. It is not clear that the results
      obtained here would be applicable to an acute patient population.

PMID- 9543207
TI  - Risk factors for depression in primary care. Findings of the TADEP project.
AB  - BACKGROUND: Depression is a common but poorly recognized disorder in primary
      care. Knowing risk factors related to depression can help doctors in diagnosing
      and treating depressive patients. METHODS: A random sample of 1643 individuals,
      aged 18 to 64, attending community health centres in Central Finland, took part
      in an inquiry with an instrument (the DEPS) measuring their depressiveness.
      RESULTS: Negative life events, poor physical health, poor marital or other
      interpersonal relationships, spouse's poor health, poor socio-economic and work
      situation and problems with alcohol were the major variables explaining the
      variance of depressive symptoms both in regression and discriminant analyses.
      CONCLUSION: In the primary care patients, negative life events, poor physical
      health, poor marital or other interpersonal relationships, spouse's poor health,
      poor socio-economic and work situation and problems with alcohol indicate high
      risk for depression; they also often accumulate in the same patients. The
      connection between risk factors and depression is stronger in males than in
      females. LIMITATION: The assessment of depression is based on the self-fulfilled
      scale and cannot, therefore, be directly generalized to clinical depression.
      Because of the cross-sectional study design, it is not possible to make any
      causal conclusion between risk factors and depression. CLINICAL RELEVANCE: By
      paying attention to the most general risk factors of depression, general
      practitioners can become more sensitive in their recognition of depression.

PMID- 9543208
TI  - Subpopulations of early separation anxiety: relevance to risk of adult anxiety
      disorders.
AB  - BACKGROUND: The present study aims to examine whether discrete subpopulations can
      be identified according to their levels of early separation anxiety (SA), and if
      so, whether such a typology of SA influences risk to particular adult anxiety
      disorders. METHODS: Mixture analysis was applied to early SA scores provided
      retrospectively by a composite group (n=1800) of adult community and patient
      samples. The distribution of adult anxiety diagnoses across the SA categories was
      assessed in a community (n=136) and a clinic (n=74) sample. RESULTS: The mixture
      analysis yielded two subpopulations according to SA scores. Odds ratios for
      assignment to the high SA category for the various anxiety disorders ranged from
      3.6 to 6.7. A logistic regression analysis revealed that when comorbidity was
      taken into account, the panic disorder-agoraphobia (PD-Ag) group was the only
      anxiety disorder to be associated with the high SA category. CONCLUSION:
      Assignment to a high early SA category appears to increase risk to adult anxiety
      disorders, particularly PD-Ag. Several possible pathways may account for such a
      risk including the persistence of separation anxiety disorder into adulthood.
      LIMITATIONS: Assessment of early SA was made using a retrospective measure and
      the samples included groups which were known to have high SA scores. CLINICAL
      RELEVANCE: Only a subpopulation of anxiety sufferers may have elevated levels of
      SA. Identification of this group may be important for early detection and
      intervention.

PMID- 9543209
TI  - Self-concept and mood: a comparative study between depressed patients with and
      without borderline personality disorder.
AB  - Within the framework of Self-Structure Theory, this study investigated the
      relationship between depressed mood and Borderline Personality Disorder (BPD) on
      self and others descriptions, with a special emphasis on the self-structure's
      valence, that is, its affective, negative and/or positive content. Seventeen DSM
      III-R unipolar depressed patients with associated BPD (DSM-III-R axis II) and
      twelve unipolar depressed patients without BPD were compared to eighteen non
      psychiatric controls on four measures of evaluation and of affective discrepancy
      of descriptions of self and others. Subjects were administered the grid repertory
      technique. The analysis of the resulting two-way valence matrix, with
      attributions as columns, and self and others as rows, showed that depressed
      patients with and without BPD differed from the non-psychiatric controls with
      regard to negativity of the descriptions. As compared with the two other groups,
      depressed patients with BPD showed a distinctive pattern characterised by the
      joint presence of a negative view of self and a larger affective discrepancy for
      others, with others being conjunctively assigned positive and negative
      attributes. Despite some limitations, the distinctive pattern evidenced
      corroborates the conflicted interpersonal relationship and is in keeping with
      clinical theorising on BPD.

PMID- 9543210
TI  - Conduct disorder and mania: what does it mean in adults.
AB  - OBJECTIVE: Because of the relationship between childhood behavior disorders and
      adult substance abuse, we hypothesized that substance abusing adult bipolars were
      more likely to have had behavior disorders as children than nonabusing bipolar
      adults. METHODS: Conduct disorder (CD) symptoms in 132 bipolar adults were
      compared by age and presence of comorbid substance use problems using data from
      the Epidemiologic Catchment Area study. RESULTS: Rates of CD were higher in
      bipolar subjects under age 30 (32.6%) versus those over (16.3% P<0.05). Young BPs
      with substance use problems (SUBST) had CD rates three times those without SUBST
      (52% vs. 14.8%) (P < 0.01). Young subjects without mania or SUBST had CD rates of
      7.75%. CONCLUSION: Substance abuse in bipolar adults may be more related to
      childhood conduct disorder than uncomplicated bipolar disorder.

PMID- 9543211
TI  - Health-related quality of life assessment in euthymic and depressed patients with
      bipolar disorder. Psychometric performance of four self-report measures.
AB  - The purpose of this study was to evaluate the psychometric properties of selected
      health-related quality of life (HRQL) self-report measures in 62 euthymic and
      depressed patients diagnosed with bipolar disorder. Patients completed the
      Quality of Life in Depression Scale (QLDS), Mental Health Index-17 (MHI-17),
      Cognitive Function Scale, and Medical Outcomes Study Short Form-36 (SF-36) at
      baseline and 8 weeks following treatment. Hamilton and Young Rating Scales were
      used to assess clinical status and validate the HRQL measures. The MHI-17,
      Cognitive Function Scale, QLDS, and SF-36 social function, vitality, role
      limitations-emotional, and mental health scales have good reliability and
      validity, and are responsive to changes in clinical status in patients with
      bipolar disorder. Although the small sample size limits generalizablity, euthymic
      and depressed outpatients with bipolar disorder appear to contribute reliable
      self reports on selected aspects of their quality of life.

PMID- 9543212
TI  - To what extent do premenstrual and interictal dysphoric disorder overlap?
      Significance for therapy.
AB  - BACKGROUND: Premenstrual dysphoria has shown a significant relationship to
      epilepsy, and its symptoms correspond to those of the interictal dysphoric
      disorder. The established treatment for interictal dysphoric disorder is explored
      as an effective treatment for premenstrual dysphoria. METHODS: Women with
      premenstrual dysphoria (the majority with epilepsy) were evaluated and treated
      systematically. RESULTS: Premenstrual disorder responded well to the combination
      of antidepressant and antiepileptic medication. CONCLUSION: Concordance of
      symptomatology between interictal and premenstrual dysphoric disorder may extend
      to treatment. LIMITATIONS: The treatment needs to be evaluated in a large series
      of women without epilepsy. CLINICAL RELEVANCE: A novel understanding and
      treatment of premenstrual dysphoria is suggested.

PMID- 9543213
TI  - Minor depressive disorder and subsyndromal depressive symptoms: functional
      impairment and response to treatment.
AB  - BACKGROUND: This study quantifies functional impairment and depressive
      symptomatology in patients with minor depressive disorder (MinD) and subsyndromal
      depressive symptomatology (SSD) before and after 8 weeks of treatment with
      fluvoxamine. Study patients were compared and contrasted with archival data from
      a sample of the general population measured by the Medical Outcome Survey Short
      Form 36. METHOD: Fifteen patients with MinD and 15 patients with SSD were
      identified from primary care clinics, referrals and newspaper advertisements.
      Patients signed informed consent and were offered open label treatment with
      fluvoxamine 25-100 mg/day. Patients were seen biweekly and measures of functional
      impairment and depressive symptomatology were gathered systematically. RESULTS:
      MinD and SSD were associated with dysfunction and disability when compared to
      archival normative data from the general population. Eight week treatment with
      fluvoxamine was associated with a substantial decrease in depressive
      symptomatology and a normalization of psychosocial functioning. CONCLUSION: This
      is the first study to quantify functional impairment and the severity of
      depressive symptomatology in a clinical sample of patients with MinD and SSD, and
      to demonstrate that treatment with a selective serotonin reuptake inhibitor
      decreases depressive symptomatology and improves psychosocial functioning.
      Placebo-controlled double-blind confirmation of these preliminary observations
      seems warranted.

PMID- 9543214
TI  - An epidemiological and clinical investigation of postpartum psychiatric illness
      in Japanese mothers.
AB  - A case note study of postpartum psychiatric illness as defined by Research
      Diagnostic Criteria (RDC) was conducted in an epidemiologically defined large
      area of Japan. The admission rate was 0.34/1000 live births. The most frequent
      diagnostic category was affective disorder (53%). "Atypical" symptoms were
      observed in 31% of all cases and were more frequent (67%) in patients with
      schizoaffective disorder. Fifty six percent of mothers developed a psychiatric
      illness within two weeks of delivery. The patients with "atypical" symptoms were
      admitted much more quickly and their length of stay in hospital was shorter.

PMID- 9543215
TI  - The clinical value of duplex surveillance following internal carotid artery
      reconstruction.
AB  - BACKGROUND: The purpose of this retrospective analysis was to evaluate the
      benefit of a yearly duplex ultrasonography of both the reconstructed and the
      contralateral internal carotid artery (ICA). METHODS: From 1985 to 1994, 1210
      unilateral, primary ICA reconstructions were performed. Although these patients
      received yearly invitations, duplex follow-up was not available in 114 patients
      (9%). RESULTS: At 5 years a stenosis of 50% or more was found in 9% and at 10
      years in 14% of patients. During the follow-up period 20 patients developed a
      stenosis of 80-99%. Ten patients had a redo-procedure. The others remained
      asymptomatic, even though one patient developed an occlusion. A stroke occurred
      in 96 patients. 58 of these had no significant stenoses. 57% of all patients had
      no significant contralateral lesion at the time of the first procedure. In only
      4% of these a contralateral CAE was performed during the follow-up. CONCLUSIONS:
      In view of the above data, we would conclude that the clinical benefit of duplex
      surveillance is doubtful.

PMID- 9543216
TI  - Transcranial duplex ultrasound: experience with contrast enhancing agents.
AB  - Transcranial duplex real time sonography (TCCS) is a non-invasive imaging
      modality that allows repetitive examinations of central nervous system vascular
      and parenchymal anatomy; a broad spectrum of cerebral pathology may be disclosed:
      vascular changes include ischemic and hemorrhagic stroke, arteriosclerotic
      vascular degeneration, arteno-venous malformations and aneurysms, as well as
      neoplastic and degenerative parenchymal disorders. Imaging was performed with a
      duplex ultrasound system, employing a 2.25 resp. 2.0 MHz phased-array transducer.
      Imaging was achieved through the acoustic bone window of the temporal bone and
      through the foramen magnum. For three-dimensional image reconstruction a
      mechanical position sensor and online video grabbing was applied. To evaluate the
      potential of a transpulmonary stable ultrasound contrast enhancing agent we used
      galactose-based SH U 508 A (Levovist, Schering, Berlin) with 1 to 6 i.v.
      injections per patient in a phase 2/3 clinical protocol. The signal to noise
      ratio is significantly improved; the Doppler signal intensity is increased by
      approx. 25 dB. Levovist was well tolerated and no adverse events occurred,
      approx. 30% of patients had a sensation of heat and slight pain at the injection
      site during and shortly after the injection. With the increase in signal
      intensity, the complete circle of Willis, the peripheral arterial branches, the
      vertebro-basilar system and the basal venous system may be depicted. In addition,
      tumour parenchyma vascularisation may be detected, as well as improved
      delineation of arteriovenous malformations and aneurysms. Three dimensional image
      reconstruction may represent a novel option in contrast enhanced transcranial
      duplex imaging including additional information about 3D structure and
      continuity.

PMID- 9543217
TI  - The importance of the Doppler angle.
AB  - We examined 118 infrainguinal grafts (103 patients) to determine the effect
      changes in the angle of theta or Doppler angle had on the accuracy of velocity
      measurements made with a duplex scanner. Four separate measurements of peak
      velocity were made on each graft. Three measurements were made with the flow
      toward the probe at 60 degrees, 50 degrees, 120 degrees (60 degrees the other
      way). The probe was then turned 180 degrees so the flow was away from the probe
      and measurements were made at 60 degrees. When the primary cursor was aligned
      with the vessel wall (Technologist A), the mean velocity at 60 degrees was 69.4
      cm/sec and 57.3 cm/sec at 50 degrees, a difference of 12 cm/sec. The same
      measurements done by Technologist B (primary cursor non aligned with the wall),
      showed a 10 cm/sec difference (60.7 and 50.5). We saw a consistent difference
      with even this small difference in the angle of theta throughout the study. The
      mean velocity obtained by Technologist A when the flow was toward the probe was
      61.7. When the probe was turned 180 degrees (flow away from the probe), the mean
      velocity was 60.5. The same measurements by Technologist B were 51.8 and 50.5.
      This indicates that the direction of the flow of blood towards or away from the
      probe does not effect the velocity measurements. Using the vessel wall to line up
      the primary cursor provides a consistent and easily reproducible reference point
      to compare measurements made on different days but is less important for single
      measurements.

PMID- 9543218
TI  - Characteristics of chronic venous insufficiency in 895 patients followed in
      general practice.
AB  - BACKGROUND: This study was designed to describe the main semiological and
      etiological characteristics of chronic venous insufficiency (CVI) and to
      determine if there was a relationship between the extent of objective signs,
      severity of symptoms and aetiology. MATERIALS AND METHODS: 895 outpatients
      presenting CVI of the lower limbs over a period of at least one year,
      irrespective of grade of severity or aetiology, were included in this
      retrospective study. They were treated with 2 different pharmaceutical forms of
      the same venoactive medication (1000 mg of micronised flavonoid fraction) for 2
      months. Organic CVI (OCVI) was classified, in stages of increasing severity,
      according to the Widmer and Porter classification. In the absence of anatomical
      lesions of the main veins or their valvular system, CVI was termed functional
      (FCVI). RESULTS: Analysis indicated that CVI was more frequent in women than in
      men (sex ratio 10:1). 26% were FCVI and 91% of OCVI were of varicose origin. The
      mean progression time of the disease was 13+/-11 years. Disease began earlier in
      women than in men (34+/-14 vs 41+/-14 years). Oedema was the first objective sign
      in 68% of patients and the only one in 20% of FCVI. Heaviness was more frequent
      in FCVI and its intensity was not related to the severity of CVI. Trophic
      complications were more frequent in the advanced stages. CONCLUSIONS: In order to
      avoid progression to more severe forms which are disabling or expensive to treat,
      a rational approach to the management of early CVI is essential.

PMID- 9543219
TI  - Conservative management of superior mesenteric and portal vein thrombosis
      associated with protein C and S deficiency. Case report.
AB  - Protein C and S, vitamin K-dependent proteins, are blood coagulation inhibitors.
      Their deficiency causes systemic thrombosis. A 35-year-old man who developed
      superior mesenteric venous thrombosis and portal vein thrombosis showed markedly
      decreased protein C and S levels. The therapeutic modality of this thrombosis
      associated with protein C and S deficiency is still debated. We treated this
      patient with systemic anticoagulation and long term total parenteral nutrition
      without surgical intervention.

PMID- 9543220
TI  - Clinical and morphological aspects of Buerger's disease.
AB  - BACKGROUND: Thirty-five patients with TAO and 35 with ASO have been studied. To
      determine differences between these two arterial diseases, we used clinical
      criteria, arteriographic and morphological methods. The peripheral (below the
      bifurcation of the popliteal artery) angiographic changes were found in TAO with
      94% sensitivity, 94% specificity and with 96% of positive predictive value. Other
      clinical diagnostic criteria for differential diagnosis had a lower value (they
      had high sensitivity and low specificity or low sensitivity and high
      specificity). RESULTS: The histologic studies confirmed the clinical diagnoses of
      Buerger's disease in 92,9% cases. The pathologic findings in TAO and ASO were
      different. CONCLUSIONS: Our investigations proved that the characteristics of
      Buerger's disease include the development of changes not only in small and medium
      size arteries or veins, but also in microcirculation.

PMID- 9543221
TI  - New method and device for assessment of functional capacity of upper extremity
      with chronic ischemia.
AB  - BACKGROUND: The aim of this study is to establish an objective diagnostic method,
      through which the functional capacity of the upper extremity with chronic
      ischemia could be best assessed. METHODS: For a 9-year period (1986-1994) 74
      patients suffering Arterial Occlusive Disease (AOD) of the upper extremity with
      chronic ischemia were treated. Fifty five of them (74.3%) were males (an average
      age of 52.4 years) and 19 females (25.6%), (an average age of 42.5 years). Forty
      nine of them (66.2%) were in second stage according to the adapted Fontain's
      classification. An original method and device have been established for the
      investigation of the abilities of the upper extremity to make repeated movements
      till they get an intermittent claudication. The apparatus consists of tree
      modules: a mechanical device, an interface adapter and a microcomputer. RESULTS:
      During the flexion of the fingers the patient overcomes the resistance of springs
      which is 1.82 Nm. An Ischemic Fatigue Index (IFI) is calculated--it gives the
      quantitative value of the functional capacity of the limb. IFI in patients in
      second stage of Chronic Arterial Ischemia (CAI) is from 0.14 to 0.76 during the
      diagnostic test and from 0.18 to 1.0 after the operative or drug treatment or
      Percutaneous Transluminal Angioplasty (PTA). A retrospective analysis shows that
      in patients who were operated on, the preoperative IFI was less than 0.50. The
      measurement of Arm-Arm Blood Pressure Index (AABPI) before treatment and after it
      in some cases shows normal values in spite of the presence of subclavian artery
      stenoses. The angiographies that were done could not help for the evaluation of
      the functional capacity of the upper extremities. The presence of pulse in 9
      patients (18.4%) does not exclude a presence of occlusion. CONCLUSIONS: IFI is a
      quantitative indicator for the upper extremity capacity. It shows whether the
      symptoms are severe enough to justify the surgery. The periodical measurement of
      IFI is a monitoring of the development of AOD.

PMID- 9543223
TI  - Cure of renovascular hypertension by percutaneous occlusion of a large idiopathic
      renal arteriovenous fistula. Case report.
AB  - Percutaneous balloon occlusion of a large hypertensive idiopathic renal
      arteriovenous fistula is reported. A lumbar thrill was noted in a 52-year-old
      hypertensive woman. Intravenous digital substraction angiography identified the
      lesion. After arteriographic assessment a percutaneous embolisation was performed
      with a releasable balloon positioned on a coaxial micro-catheter. Immediate post
      procedural angiographic control demonstrated complete occlusion with a small
      segmental area of renal hypoperfusion. The lumbar thrill disappeared.
      Normalisation of the blood pressure was noted two days later and confirmed eight
      months later. Persistent occlusion of the fistula was angiographically confirmed,
      whereas the area of renal hypoperfusion had partially decreased. Releasable
      balloon percutaneous embolisation appears to be a safe alternative to surgery in
      the treatment of large renal arteriovenous fistulas.

PMID- 9543222
TI  - Treatment of severe Raynaud's syndrome by injection of autologous blood
      pretreated by heating, ozonation and exposure to ultraviolet light (H-O-U)
      therapy.
AB  - OBJECTIVE: To determine the effect of re-injection of small samples of autologous
      blood, pretreated with heat, ozone and ultraviolet light (H-O-U therapy) in
      patients with severe Raynaud's syndrome. EXPERIMENTAL DESIGN: Open trial in 4
      patients. SETTING: Temperature/humidity controlled vascular laboratory. PATIENTS:
      Severe Raynaud's syndrome of more than 5 years duration and defined as more than
      5 attacks daily or 10 attacks in one week, at least half of which were painful
      and lasting for more than 30 minutes. Three patients were refractory to infusions
      of Iloprost. INTERVENTIONS: Patients were treated daily or on alternate days for
      a two to three weeks period by re-injection of citrated autologous blood pre
      treated with heat, ozone and ultraviolet light (H-O-U therapy). MEASURES:
      Clinical observations; mean equilibrated hand temperature (infrared
      thermography); distributive and microcirculatory blood-flow (venous occlusion
      strain-gauge plethysmography, infrared photoplethysmography, laser Doppler
      flowmetry) iontophoresis of acetylcholine and sodium nitroprusside; estimations:
      serum levels of 6-keto-PGF1alpha and serum levels of anti-hsp65 antibody.
      RESULTS: Reduction or abolition of Raynaud's attacks for at least three months
      after treatment. Mean equilibrated hand temperature increased but did not
      normalise. Blood flow parameters improved but did not reach statistical
      significance. Iontophoresis of acetylcholine showed an increase in laser Doppler
      flowmetry which was statistically significant. Serum levels of 6-keto-PGF1alpha,
      fell significantly in three patients. Serum levels of anti-hsp65 antibody fell in
      the one patient which was followed sequentially. CONCLUSIONS: H-O-U therapy may
      prove useful in patients with severe Raynaud's syndrome.

PMID- 9543224
TI  - Effect of gemfibrozil on early carotid atherosclerosis in diabetic patients with
      hyperlipidaemia.
AB  - BACKGROUND: An increased thickness of the carotid artery wall is thought to be a
      sign of early atherosclerosis. We have investigated the effects of gemfibrozil in
      asymptomatic diabetic hyperlipidaemic subjects on the 12-month progression of
      arterial wall thickness. METHODS: Forty non-insulin-dependent diabetics with
      hyperlipidaemia and without hypertension were studied. After a 4-week run-in-diet
      phase, oral gemfibrozil was administered (900 mg once daily) in 20 patients
      randomly selected, while 20 subjects were treated only with diet. The two groups
      were matched for age, sex, body mass index (BMI), duration of diabetes and
      glycaemic control. Arterial wall thickness was measured as the mean of the
      maximum intima of media thickness (IMT) in 16 carotid segments by B-mode
      ultrasound. RESULTS: Baseline size of IMT and lipid values were similar in both
      groups. The IMT increase over 12 months was 5% in the gemfibrozil group vs 15.2%
      in subjects treated by diet alone. CONCLUSIONS: We conclude that gemfibrozil
      treatment may be useful in decreasing the progression rate of arterial wall
      thickness.

PMID- 9543225
TI  - Effect of cooling on vascular smooth muscle response to endothelin-1 in human and
      rat veins.
AB  - BACKGROUND: The plasma level of endothelin-1 is locally increased during cooling
      but the net vasoconstrictor effect will be dependent on temperature effects on
      the vascular smooth muscle reactivity in response to the polypeptide. The aim of
      this study was to investigate the effect of cooling on the vascular smooth muscle
      response to endothelin-1 in human and rat veins. METHODS: Registration of
      vascular smooth muscle activity in vitro in vessel preparations from normal
      subjects. SETTING: Laboratory. PATIENTS AND ANIMALS: Superficial hand veins from
      14 patients undergoing hand surgery and external jugular veins from 14 rats.
      INTERVENTIONS: Effects of endothelin-1, after denudation of the endothelium and
      during cooling, were compared with controls without these interventions. RESULTS:
      At 37 degrees C, endothelin-1 induced a concentration-dependent contraction in
      the human hand and rat jugular veins. The sensitivity to endothelin-1 was
      enhanced in segments without endothelium. At 37 degrees C, no relaxation in
      response to endothelin-1 was observed. Cooling to 10 degrees C did not alter
      precontraction achieved by endothelin-1 at 37 degrees C in the human hand veins,
      while it depressed the precontraction in the rat jugular vein. The effect of cold
      was reversible. Removal of the endothelium did not alter the response to cooling.
      CONCLUSIONS: The maintained reactivity in response to endothelin-1 during cooling
      of the human vessels suggests that the reported increase in endothelin-1 levels
      due to local cooling could contribute in the pathophysiology of peripheral
      vasospasm in humans.

PMID- 9543226
TI  - Endothelin-1 in arterial hypertension after cold pressor test.
AB  - BACKGROUND: We assessed plasma endothelin-1 (ET-1) concentrations in a group of
      hypertensive subjects in order to determine the possible presence of a disorder
      of ET-1 production and release. METHODS: A selected cohort of hypertensive
      subjects was compared with a control group. Plasma levels of ET-1 in baseline
      conditions and after cold the pressor test (CPT) were measured. All subjects were
      studied as outpatients. Twenty-one male hypertensive patients were compared with
      15 male controls. The hypertensive patients had undergone clinical examinations
      to rule out the presence of vascular damage. Clinical examination of the controls
      was performed to rule out hypertension. Patients with essential hypertension were
      21 males, age: 57+/-7 years, body mass index 22.3+/-11.2 kg/m2. We assessed
      plasma ET-1 in baseline conditions and after a cold pressor test. RESULTS: Means
      +/-SD baseline concentrations of ET-1 were 12.47+/-2.41 pg/ml in hypertensives
      and 8.2+/-3.8 pg/ml in controls (p<0.01). Mean +/-SD post CPT plasma ET-1 was
      12.55+/-2.83 pg/ml in hypertensive subjects and 8.6+/-1.9 pg/ml in controls
      (p<0.01). CPT did not modify plasma ET-1 concentrations in either group. CPT
      significantly raised arterial pressure only in hypertensive subjects.
      CONCLUSIONS: These results lead us to postulate the presence of a disorder of ET
      1 production and release in hypertensive subjects.

PMID- 9543227
TI  - Plasma adrenomedullin in cerebrovascular disease: a possible indicator of
      endothelial injury.
AB  - BACKGROUND: Cultured vascular endothelial and smooth muscle cells actively
      produce adrenomedullin, a novel vasodilator peptide discovered in human
      pheochromocytoma tissue. This present study was designed to determine whether the
      plasma level of adrenomedullin is a useful indicator for estimating the degree of
      endothelial injury in patients with atherosclerotic disease. METHODS: We used a
      radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients
      with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in
      10 subjects without symptomatic cerebrovascular disease. We also measured the
      plasma concentrations of thrombomodulin and endothelin as markers of endothelial
      injury. The patients were divided into three groups (A, B, and C) on the basis of
      the number of risk factors for atherosclerosis: hypertension, hyperlipidemia,
      smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A
      (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2
      years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more
      risk factors. RESULTS: The plasma concentration of adrenomedullin in these
      patients showed a significant positive correlation with age (r=0.33, p<0.05), as
      well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and
      endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of
      adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be
      higher in Group B and to be significantly higher in Group C as compared to Group
      A. Plasma adrenomedullin concentrations did not, however, significantly differ
      between the infarction and haemorrhage patients. CONCLUSIONS: These findings
      suggest that the plasma adrenomedullin concentrations reflect the degree of
      endothelial injury in patients with atherosclerotic disease.

PMID- 9543228
TI  - Conditioned fear stress induces ethanol-associated place preference in rats.
AB  - The purpose of the present study was to establish ethanol-induced place
      preference under conditioned fear stress (exposure to an environment paired
      previously with electric foot shock) in rats by using the conditioned place
      preference paradigm. The administration of ethanol (300 mg/kg, i.p.) with
      conditioned fear stress, but not without conditioned fear stress, induced a
      marked and significant place preference. Furthermore, additional exposure to
      conditioned fear stress immediately before the post-conditioning test further
      enhanced the development of ethanol-induced place preference. These results
      suggest that psychological stress may play an important role in the development
      of ethanol-induced place preference, and the present method may be useful for
      studying the mechanism of the rewarding effect of ethanol.

PMID- 9543229
TI  - 'Candyflipping': synergistic discriminative effect of LSD and MDMA.
AB  - The co-administration of D-lysergic acid diethylamide (LSD; 'Acid') and 3,4
      methylenedioxymethamphetamine (MDMA; 'Ecstasy'; 'XTC'), has reached a prevalence
      that has allowed for the street terminology 'candyflipping' to describe the
      combination. Internet sites indicate a significant enhancement of central effects
      with their simultaneous use. In this preliminary observation, male Fawn-Hooded
      rats were trained to discriminate 1.5 mg/kg MDMA and were, subsequently, tested
      with doses of MDMA (0.15 mg/kg) or LSD (0.04 mg/kg) that each produced a saline
      like response. Co-administration of these doses of MDMA and LSD synergized to
      produce a maximal MDMA-like response. The possible mechanism for synergistic
      action upon central serotonergic neurons is discussed to explain the observed
      effect.

PMID- 9543230
TI  - Meta-chlorophenylpiperazine induced changes in locomotor activity are mediated by
      5-HT1 as well as 5-HT2C receptors in mice.
AB  - 1-(Meta-chloro)phenylpiperazine (m-CPP) is a 5-HT receptor agonist which has been
      purported to be relatively selective for the 5-HT2C receptor. In particular, the
      hypolocomotion produced by m-CPP has been suggested to be mediated by 5-HT2C
      receptors. m-CPP binds with high affinity to 5-HT1 as well as 5-HT2 receptors,
      thus effects of m-CPP on locomotor activity may be due to the physiologic
      summation of the actions of m-CPP at 5-HT1 as well as 5-HT2 receptors. The
      present study investigated the effects of m-CPP alone and in the presence of the
      5-HT2 receptor antagonist 6-methyl-1-(-methyethyl)-ergoline-8beta-carboxylic acid
      2-hydroxy-1-methylpropyl ester maleate (LY53857), the 5-HT1A receptor antagonist
      N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2pyridinyl)c
      yclohexanecarboxamide trihydrochloride (WAY 100,635), and the 5-HT(1B/1D)
      receptor antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4
      corbox ylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]amide (GR 127935)
      on locomotor activity. Administration of m-CPP alone (0.3-10 mg/kg) produced a
      dose-related decrease in locomotor activity. The 5-HT(1B/1D) receptor antagonist
      GR 127935 (3.0 mg/kg) in combination with m-CPP produced a slight leftward shift
      of the dose-response curve of m-CPP. The 5-HT1A receptor antagonist WAY 100,635
      (1.0 mg/kg) in combination with m-CPP did not alter the m-CPP dose-response
      curve. The non-selective 5-HT2 receptor antagonist LY53857 (1.0 mg/kg) in
      combination with m-CPP unmasked a hyperlocomotion produced by m-CPP. Furthermore,
      the hyperlocomotion produced by m-CPP in the presence of LY53857 (1.0 mg/kg) was
      blocked by both the 5-HT(1B/1D) receptor antagonist GR 127935 (3.0 mg/kg) and the
      5-HT1A receptor antagonist WAY 100,635 (1.0 mg/kg). The present results
      demonstrate that the hyperlocomotion seen with the combination of m-CPP and
      LY53857 is mediated by 5-HT1 receptors. Taken together the data indicate that m
      CPP affects locomotor activity by the physiologic summation of agonist activity
      at the 5-HT2C receptor as well as the 5-HT1 receptor family.

PMID- 9543231
TI  - Properties of ginseng saponin inhibition of catecholamine secretion in bovine
      adrenal chromaffin cells.
AB  - To investigate the relationship between the inhibitory effects of ginseng
      saponins (ginsenosides) on acetylcholine-evoked secretion of catecholamines and
      the structures of ginsenosides, we examined the effects of ginsenoside-Rg3 and 
      Rh2, which are panaxadiol saponins, 20(R)- and 20(S)-ginsenoside-Rg2, which are
      epimers involving the hydroxyl group at C-20 of sapogenin, and other plant
      saponins on the acetylcholine-evoked secretion of catecholamines from cultured
      bovine adrenal chromaffin cells. The ginsenoside-Rg3 (1-100 microM) and -Rh2 (10
      100 microM) greatly reduced the acetylcholine-evoked secretion in a concentration
      dependent manner comparable to that of ginsenoside-Rg2, a panaxatriol saponin,
      which was the most potent inhibitor in our previous study. 20(R)- and 20(S)
      ginsenoside-Rg2 (1-100 microM) similarly reduced the acetylcholine-evoked
      secretion. In contrast, saikosaponin-a, glycyrrhizin and the cardiac glycosides
      (100 nM-100 microM), digitoxin and digoxin, had no significant inhibitory effect
      on catecholamine secretion. Saikosaponin-c (10-100 microM), however, had an
      inhibitory effect, which was less than that of ginsenoside-Rg2 and -Rg3. These
      results strongly suggest that the inhibitory effects of ginsenosides on the
      acetylcholine-evoked secretion of catecholamines from bovine adrenal chromaffin
      cells are a unique property of ginseng. Further, the relationship between the
      inhibitory effects and the structures of ginsenosides is discussed.

PMID- 9543233
TI  - Time course of chronic diazepam effects on the auditory evoked potential of the
      rat.
AB  - The time course of chronic diazepam effects on auditory evoked potentials was
      studied in rats. Auditory evoked potentials were elicited by background and
      target tones in a passive oddball paradigm. Diazepam was administered by slow
      release implants to establish constant blood concentrations. Recordings were made
      during 21 days of treatment and 9 days after treatment ceased. Diazepam increased
      the amplitude of the P40 component and decreased the amplitude of the P72-P102
      components elicited by background tones. Diazepam increased the amplitude of the
      P40-P48 component and decreased that of the N58 component elicited by target
      tones. These effects remained constant during treatment. Diazepam further
      decreased the amplitude of the P102 component elicited by target tones. This
      effect became more distinct over time. No group differences were found 9 days
      after treatment. The constant drug effects on middle-latency components (P40-P48)
      might reflect diazepam-induced changes in sensory information processing. The
      decreased long-latency component (P102) might reflect a diminished attention to,
      or discrimination of, target tones. The time course of this effect might reflect
      diazepam-enhanced habituation.

PMID- 9543232
TI  - Anticonvulsant effect of polyunsaturated fatty acids in rats, using the cortical
      stimulation model.
AB  - Recent studies have shown that long-chain polyunsaturated fatty acids can prevent
      cardiac arrhythmias, attributed to the reduction in excitability of
      cardiomyocytes, owing mainly to a shift in hyperpolarizing direction of the
      inactivation curves of both Na+ and Ca2+ currents and to a slowed recovery from
      inactivation. Qualitatively similar effects of polyunsaturated fatty acids on
      inactivation parameters have been observed in freshly isolated hippocampal
      neurons. Since the same effects are presumed to underlie the action of some
      established anticonvulsant drugs, polyunsaturated fatty acids might have an
      anticonvulsant action as well. We have investigated this for eicosapentaenoic
      acid, docosahexaenoic acid, linoleic acid and oleic acid, employing cortical
      stimulation in rats, a seizure model allowing the determination of the full
      anticonvulsant effect-time profile in freely moving, individual animals. I.v.
      infusion of 40 micromol of eicosapentaenoic acid or docosahexaenoic acid over a
      period of 30 min, modestly increased the threshold for localized seizure activity
      after 6 h by 73 +/- 13 microA (mean +/- S.E.M.; n = 7) and 77 +/- 17 microA (n =
      7), respectively, and the threshold for generalized seizure activity by 125 +/-
      20 and 130 +/- 19 microA, respectively (P < 0.001). The thresholds remained
      elevated for 6 h after infusion, but returned to baseline the next day. Free
      plasma concentrations in rats treated with eicosapentaenoic acid or
      docosahexaenoic acid, averaged 5.7 +/- 1.6 microM (n = 4) for eicosapentaenoic
      acid and 12.9 +/- 1.8 microM (n = 5) for docosahexaenoic acid at the end of
      infusion, but declined to undetectable levels within 3 h. Linoleic acid and oleic
      acid were less effective. Possible mechanisms for the modest anticonvulsant
      effect but of long duration with the polyunsaturated fatty acids are discussed.

PMID- 9543234
TI  - Acute effects of morphine on the expression of mRNAs for NMDA receptor subunits
      in the rat hippocampus, hypothalamus and spinal cord.
AB  - The acute effects of subcutaneously injected morphine on transcripts of the NMDA
      receptor subunits NR1, NR2A and NR2B in certain areas of the central nervous
      system of male rats were examined by Northern blot analysis. The result clearly
      indicated that a single dose (10 mg/kg) of the opioid alters the expression of
      the mRNA for receptor subunits in the hippocampus and hypothalamus 4 h after drug
      injection. No change in the mRNA levels was observed 30 min following injection,
      and after 24 h most of the levels were restored to control values. The
      observation suggests that morphine affects this type of glutamate receptor
      already in the acute phase of its administration.

PMID- 9543235
TI  - WAY 100,635 enhances both the 'antidepressant' actions of duloxetine and its
      influence on dialysate levels of serotonin in frontal cortex.
AB  - The mixed serotonin and noradrenaline reuptake inhibitor, duloxetine, (5.0 mg/kg,
      s.c.), increased levels of serotonin (220%), dopamine (180%) and noradrenaline
      (470%) in individual dialysates of frontal cortex of freely moving rats. Its
      influence on serotonin, but not dopamine or noradrenaline, levels was enhanced by
      the 5-HT1A receptor antagonist, WAY 100,635 (N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide 3HCl) (0.16 mg kg(-1),
      s.c). In the forced swimming test, although duloxetine was inactive alone, it
      dose dependently reduced immobility in the presence of WAY 100,635. Thus,
      blockade of 5-HT1A (auto)receptors selectively facilitates the influence of
      duloxetine on serotonin levels in the frontal cortex in rats and, in the forced
      swimming model, enhances its 'antidepressant' properties in parallel.

PMID- 9543236
TI  - Activation of neurotensin receptors in the prefrontal cortex stimulates midbrain
      dopamine cell firing.
AB  - The effects of medial prefrontal cortex microinjections of 3 nmol/0.5 microl of
      neurotensin-(1-13), the inactive fragment neurotensin-(1-8), or vehicle on the
      firing rate of midbrain dopamine neurons were studied in anesthetized rats.
      Twelve of 19 cells tested with neurotensin-(1-13) showed an average 20-25%
      increase in firing rate between 10 and 20 min after the injection. This effect
      was not mimicked by neurotensin-(1-8) (9 cells), nor by a control injection (10
      cells) suggesting that it is mediated by high-affinity neurotensin receptors.
      These results suggest that activation of neurotensin receptors in the medial
      prefrontal cortex can modulate neural activity of a subpopulation of midbrain
      dopamine neurons.

PMID- 9543237
TI  - Inhibition of protein phosphatases alters the expression of morphine tolerance in
      mice.
AB  - Recently our laboratory found that tolerance to morphine-induced antinociception
      could be completely reversed with intracerebroventricular (i.c.v.) administration
      of a protein kinase A inhibitor, whereas intrathecal (i.t.) administration of the
      inhibitor produced hyperalgesia in morphine-tolerant mice. In the experiments
      described here, we sought to characterize further the role of phosphorylation
      events in supraspinal versus spinal opioid-mediated pain pathways and how such
      events might be involved in the development of antinociceptive tolerance. Two
      phosphatase inhibitors were administered centrally to determine whether they
      affected morphine-induced antinociception in naive or chronically morphine
      treated mice. By the i.c.v. route, okadaic acid enhanced morphine-induced
      antinociception in tolerant mice and produced toxicity by the i.t. route. The
      calcineurin inhibitor ascomycin had no effect on antinociception following acute
      or chronic morphine treatment. These results suggest that increased activity of
      protein phosphatase types 1 and/or 2A in the brain may contribute to the
      development of morphine tolerance.

PMID- 9543238
TI  - Antagonism of alpha1-adrenoceptor agonist-induced responses by rilmenidine in
      vascular smooth muscle.
AB  - The effect of the centrally acting antihypertensive agent, rilmenidine, was
      examined on the contractile properties of isolated rat portal vein strips and on
      the free cytosolic [Ca2+] ([Ca2+]i) in isolated myocytes. Rilmenidine (1-30
      microM) relaxed strips precontracted with noradrenaline. This effect was not
      inhibited by the alpha2-adrenoceptor antagonist, yohimbine, and was not mimicked
      by the alpha2-adrenoceptor agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6
      quinoxalinamine (UK 14,304). Rilmenidine dose dependently shifted to the right
      the concentration-response curves to noradrenaline and to phenylephrine but not
      that to carbachol. Rilmenidine alone (0.1-30 microM) caused a contraction which
      maximally corresponded to 18% of the maximal noradrenaline-induced contraction.
      This effect was not produced by UK 14,304, was not affected by yohimbine, but was
      inhibited by the alpha1-adrenoceptor antagonist, prazosin. In isolated myocytes,
      rilmenidine reduced the noradrenaline-induced [Ca2+]i increase but alone, it
      produced a rise in [Ca2+]i, the peak amplitude of which averaged 15% of the
      noradrenaline-induced transient [Ca2+]i rise. It is concluded that rilmenidine
      acts as a partial agonist of alpha1-adrenoceptors of vascular smooth muscle,
      causing relaxation of vessels precontracted by full agonists of alpha1
      adrenoceptors.

PMID- 9543239
TI  - Endothelin-1 and unstable angina: effect of either endothelin ET(A) or ET(B)
      receptor antagonism in a locally injured canine coronary artery.
AB  - The role of endogenous endothelin-1 in variant angina was investigated using two
      endothelin receptor antagonists: LU 135252 (ET(A)) and BQ 788 (ET(B)). Cyclic
      flow reductions were induced in a coronary artery of mongrel dogs by combining
      critical stenosis with endothelial injury. One hour after induction of cyclic
      coronary flow reductions the dogs were randomized to intravenous treatment with
      either saline, or LU 135252 (10 mg kg(-1)), or BQ 788 (0.1 mg kg(-1)). Cyclic
      coronary flow reductions were monitored for two hours after drug and remained
      constant in controls as well as after BQ 788. LU 135252 reduced the number of
      cyclic coronary flow reductions significantly (about 50%) without effects on
      hemodynamics or hemostasis.

PMID- 9543240
TI  - Effects of FK409, a nitric oxide donor, on renal responses to renal nerve
      stimulation in anesthetized dogs.
AB  - We examined the effects of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3
      hexenamide (FK409), a nitric oxide (NO) donor, on renal actions and
      norepinephrine overflow induced by renal nerve stimulation in anesthetized dogs,
      with or without N(G)-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal
      nerve stimulation at a low frequency (0.5-2.0 Hz) produced significant decreases
      in urine flow and urinary excretion of Na+ and increases in norepinephrine
      secretion rate. Renal nerve stimulation at a high frequency (2.5-5.0 Hz) which
      diminishes renal hemodynamics, elicited more marked decreases in urine formation
      and increases in norepinephrine secretion rate. Intrarenal arterial infusion of
      FK409 (0.25 microg/kg/min) failed to alter renal actions and increases in
      norepinephrine secretion rate in response to both low- and high frequency renal
      nerve stimulation. When NOARG (40 microg/kg/min) was administrated intrarenally,
      low-frequency renal nerve stimulation caused a potent antidiuresis and renal
      vasoconstriction. The renal nerve stimulation-induced increase in norepinephrine
      secretion rate was markedly enhanced by NOARG infusion. Simultaneous infusion of
      FK409 markedly attenuated the NOARG-induced enhancement of renal actions and
      increases in norepinephrine secretion rate, in response to low-frequency renal
      nerve stimulation. These results suggest that exogenous NO suppresses the renal
      nerve stimulation-induced norepinephrine overflow and renal actions in NO
      depleted conditions. We also propose that endogenous NO functions tonically as an
      inhibitory modulator of renal noradrenergic neurotransmission.

PMID- 9543241
TI  - Pharmacology of the peptidomimetic, MEN 11149, a new potent, selective and orally
      effective tachykinin NK1 receptor antagonist.
AB  - In this study we investigated the pharmacological properties of MEN 11149, 2-(2
      naphthyl)-1-N-[(1R,2S)-2-N-[1(H)indol-3-ylcarbonyl]aminocy clohexanecarbonyl]-1
      [N'-methyl-N'-(4-methylphenylacetyl)]di aminoethane, a novel partially retro
      inverse pseudo peptide antagonist of tachykinin NK1 receptors. MEN 11149 potently
      inhibits the binding of [3H]substance P to tachykinin NK1 sites in IM9 cells (pKi
      = 8.5 +/- 0.1). The compound is highly specific for the human tachykinin NK1
      receptors, since it has negligible effects (pKi < 6) on the binding of specific
      ligands to tachykinin NK2, NK3 receptors and a battery of central and peripheral
      receptors or ion channels. The tachykinin NK1 receptor antagonism of MEN 11149
      appears to be insurmountable since, in saturation binding experiments, both K(D)
      and Bmax are significantly affected by incubation with the compound (1-30 nM). In
      isolated guinea-pig ileum, MEN 11149 (0.1-100 nM) shifts to the right in a non
      parallel way the substance P methyl ester-induced cumulative concentration
      response curve with progressive inhibition of the maximal response (pK(B) = 9.6
      +/- 0.1). When tested for reversibility at 5 nM in the same preparation, the
      compound displays a slow dissociation rate compared to the fast dissociation rate
      with FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N
      methy l-N-phenylmethyl-L-3-(2-naphthyl)alaninamide) at 5 nM. In the same
      preparation, MEN 11149 (10 microM) did not affect the cumulative concentration
      response curve to acetylcholine. In vivo, MEN 11149 dose dependently antagonizes
      [Sar9,Met(O2)11]substance P-induced bronchoconstriction in anaesthetized guinea
      pigs (ID50 = 83 +/- 31 nmol/kg i.v.). The duration of the effect exceeds 3 h. MEN
      11149 does not affect the bronchoconstriction induced by neurokinin A. The
      compound dose dependently inhibits [Sar9,Met(O2)11]substance P-induced plasma
      protein extravasation in guinea-pig bronchi whether administered intravenously
      (ID50 = 0.22 +/- 0.02 micromol/kg) or orally (ID50 = 0.97 +/- 0.21 micromol/kg).
      These results demonstrate that MEN 11149 is a potent, highly selective and orally
      effective insurmountable antagonist of tachykinin NK1 receptors with a long
      duration of action.

PMID- 9543242
TI  - Tachykinin NK2 receptors predominantly mediate tachykinin-induced contractions in
      ovine trachea.
AB  - In vitro studies were conducted to characterize the contractile effects of
      tachykinins in normal ovine trachea with a view in the future to compare
      tachykinin contractile responses in allergic tissue. Tracheal smooth muscle
      strips were prepared for in vitro studies of isometric contraction in response to
      cumulative addition of carbachol, acetylcholine, histamine, neuropeptide gamma,
      substance P, neurokinin A, neurokinin B, [Sar9, Met(O2)11]substance P,
      [Nle10]neurokinin A-(4-10), and [Succinyl-Asp6, Me-Phe8]substance P-(6-11)
      (senktide). The rank order of potency was neuropeptide gamma > carbachol >
      neurokinin A > or = [Nle10]neurokinin A-(4-10) > acetylcholine > or = histamine.
      Phosphoramidon enhanced the contractile response to neurokinin A and substance P,
      but not to neuropeptide gamma, [Sar9, Met(O2)11]substance P or senktide. Repeated
      cumulative concentration responses for acetylcholine, substance P, neurokinin A,
      [Sar9, Met(O2)11]substance P and histamine were also conducted to test for
      tachyphylaxis. No tachyphylaxis to acetylcholine, substance P, or neurokinin A
      was observed, however, [Sar9, Met(O2)11]substance P and histamine did exhibit
      tachyphylaxis. Atropine had no effect on tracheal contractions to neurokinin A
      and substance P, while [Sar9, Met(O2)11]substance P contractions were atropine
      sensitive. Pyrilamine did not affect substance P-induced tracheal smooth muscle
      contractions, indicating that the response to substance P was not mediated by
      histamine release. These results show that, in vitro, natural tachykinins induce
      tracheal smooth muscle contraction predominantly by a direct effect mediated by
      tachykinin NK2 receptors, and a small tachykinin NK1 receptor mediated
      cholinergic mechanism.

PMID- 9543243
TI  - The role of cGMP in the relaxation to nitric oxide donors in airway smooth
      muscle.
AB  - The aim of this study was to determine the effect of the soluble guanylyl cyclase
      inhibitors methylene blue and LY83583 (6-anilino-5,8-quinolinedione) on
      relaxation and increases in intracellular guanosine 3',5'-cyclic monophosphate
      (cGMP) concentration ([cGMP]i) induced by sodium nitroprusside, 3
      morpholinosydnonimine (SIN-1) and diethylamine-nitric oxide (NO) in porcine
      tracheal smooth muscle in vitro. We measured (1) the effect of NO donors on
      isometric force and [cGMP]i and (2) the ability of methylene blue and LY83583 to
      antagonize these effects. In muscle strips contracted with carbachol (0.1-0.3
      microM), both sodium nitroprusside and diethylamine-NO caused relaxation and an
      increase in [cGMP]i. By contrast, SIN-1 caused a relaxation which was not
      associated with a concomitant increase in [cGMP]i. Methylene blue (10 microM) and
      LY83583 (10 microM) completely blocked the increase in [cGMP]i induced by sodium
      nitroprusside and diethylamine-NO; however substantial relaxation remained. It is
      concluded that in porcine airway smooth muscle, (1) relaxation induced by some NO
      donors may occur without a concomitant increase in [cGMP]i; and (2) whereas
      relaxation induced by some NO donors may be associated with increases in [cGMP]i,
      the relaxation is not completely dependent upon it.

PMID- 9543244
TI  - Pharmacological profiles of new orally active nonpeptide tachykinin NK1 receptor
      antagonists.
AB  - Pharmacological profiles of new orally active amide-based tachykinin NK1 receptor
      antagonists, N-[3,5-bis(trifluoromethyl)benzyl]-5-(4-fluorophenyl)-7,8-dihydro
      N,7-di methyl-8-oxo-1,7-naphthyridine-6-carboxamide (referred to as compound I)
      and two related compounds (compounds II and III), were compared with that of (+)
      (2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994), another
      nonpeptide tachykinin NK1 receptor antagonist. Compounds I, II, III and CP-99,994
      caused parallel rightward shifts of the concentration-response curve of substance
      P in the guinea-pig ileum pretreated with atropine, mepyramine and indomethacin,
      with the pA2 values of 8.70, 7.56, 8.41 and 8.27, respectively. These antagonists
      did not alter the concentration-response curve of acetylcholine in the guinea-pig
      ileum nor that of neurokinin A in the rat vas deferens. Furthermore, contractile
      responses to senktide of the rat portal vein were not affected by these
      antagonists. In the isolated neonatal gerbil spinal cord pretreated with
      tetrodotoxin, substance P produced a dose-dependent depolarization of ventral
      roots. Compounds I, II, III and CP-99,994 caused parallel rightward shifts of the
      concentration-response curve of substance P in the spinal cord with the pA2
      values of 7.07, 5.93, 6.40 and 7.26, respectively. In contrast, these antagonists
      did not affect the concentration-response curve of L-glutamate. These results
      suggest that compounds I, II and III are selective antagonists for tachykinin NK1
      receptor both in peripheral tissues and the central nervous system.

PMID- 9543245
TI  - Effect of a cardiotonic agent, MCI-154, on the contractile properties of skinned
      skeletal muscle fibers.
AB  - We have studied the effect of a cardiotonic agent, MCI-154 (6-[4-(4
      pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride trihydrate), on
      the contractile properties and adenosine triphosphatase (ATPase) activity of
      chemically skinned rabbit skeletal muscle fibers. As in cardiac muscle, MCI-154
      potentiated isometric tension and improved isometric tension cost at full Ca2+
      activation. It showed little Ca2+-sensitizing effect. In contrast to its effect
      on cardiac muscle, however, MCI-154 decreased all the kinetic parameters tested
      (shortening velocity, the rate of rise of tension, and actomyosin ATPase
      activity). All the results are explainable if MCI-154 acts directly on skeletal
      actomyosin and inhibits a reaction step(s) of the ATPase cycle later than the
      force-generating event. The qualitative difference between cardiac and skeletal
      muscles in the responsiveness to this class of cardiotonic agents (MCI-154 and
      EMD 53998, a thiadiazinone derivative) is most readily understood if the agents
      have two independent actions, one on troponin and the other on actomyosin itself,
      the latter being dominant in skeletal muscle.

PMID- 9543246
TI  - Histamine H3 receptor desensitization in the guinea-pig ileum.
AB  - Histamine H3 receptor ligands are usually tested in guinea-pig intestine
      preparations. A possible desensitization of agonist-induced twitch inhibition was
      studied in longitudinal muscle-myenteric plexus from ileal segments. A cumulative
      concentration-response curve for R-alpha-methylhistamine was made; when a second
      curve was made 30 min afterwards, a marked decrease of pD2 and a more modest
      decrease of Emax were observed without changes in tissue sensitivity to
      electrical stimulation or morphine inhibition. At 120 min, pD2 and Emax were not
      different from those for the first curve. Receptor desensitization seems
      homologous and reversible and could interfere with repetitive testing of
      histamine H3 receptor ligands.

PMID- 9543247
TI  - Acute glucosuria after continuous glucocorticoid loading in the rat in vivo.
AB  - We investigated the effects of the continuous infusion of various steroids in
      rats on renal tubular reabsorption of glucose in vivo to elucidate the
      pathogenesis of steroid-induced glucosuria. Urinary glucose excretion increased
      60 min after administration of dexamethasone (2.38 mM). By 120 min, urinary
      excretion of glucose was three times higher in the dexamethasone group than in
      the control group (24.1 +/- 4.6 versus 72.4 +/- 16.7 micromol); the plasma level
      of glucose did not increase. Dexamethasone had no effect on the resorption of 1,5
      anhydro-D-glucitol, which is a glucose-resembling polyol that is actively
      absorbed by the renal tubules as glucose. Neither estradiol nor progesterone
      increased urinary excretion of glucose. These findings suggest that continuous
      administration of a high-dose glucocorticoid selectively influences the glucose
      reabsorption system in the kidney.

PMID- 9543248
TI  - Zn2+ inhibits nitric oxide formation in response to lipopolysaccharides:
      implication in its anti-inflammatory activity.
AB  - There is compelling evidence to indicate an anti-inflammatory action of Zn2+.
      Most inflammatory diseases are associated with an increase of the inducible form
      of nitric oxide (NO) synthase. Additionally, inflammatory mediators such as
      histamine or bradykinin stimulate the constitutive NO synthase. Thus, the present
      study was undertaken to investigate whether Zn2+ inhibits production of inducible
      NO synthase and/or constitutive NO synthase activity to produce NO.
      Lipopolysaccharide, 5 mg/kg i.v., administered to Zn2+-deficient (ZD) rats, rats
      supplemented with Zn2+ sulfate (ZG), 10 mg/kg s.c., or controls resulted in a
      significant reduction of their serum Zn2+. The levels of N(G)-nitro-L-arginine
      methylester (L-NAME)-sensitive cyclic GMP (cGMP) in aortas isolated from ZD or ZG
      were significantly lower than those obtained from control animals. Zinc (100-150
      microM) produced a dose-dependent inhibition of lipopolysaccharide or interleukin
      1beta-induced NO formation in isolated rat aortic smooth muscle cells. Compared
      to cyclohexamide or actinomycin-D, the time course of inhibition of NO formation
      by 150 microM Zn2+ did not suggest an effect of Zn2+ on inducible NO synthase
      protein synthesis. Moreover, Zn2+ (150 microM) significantly reduced the rate of
      conversion of [3H]arginine to [3H]citrulline in lung homogenates from
      lipopolysaccharide-treated rats. Incubation of rat aortic smooth muscle cells and
      bovine pulmonary artery endothelial cell co-cultures with Zn2+ (150 microM)
      caused a significant reduction in basal and bradykinin- or A-23187-induced
      formation of cGMP. Thus, our results indicate that Zn2+ is capable of inhibiting
      lipopolysaccharide- or interleukin-1beta-induced NO formation as well as NO
      formation by constitutive NO synthase basally or in response to bradykinin or A
      23187, and may explain the reported anti-inflammatory activity of Zn2+.

PMID- 9543249
TI  - Amino acid release during volume regulation by cardiac cells: cellular
      mechanisms.
AB  - Mechanisms of amino acid efflux during volume regulation in hypoosmotically
      treated isolated rat hearts were studied by collecting the coronary artery
      perfusate and analysis by high pressure liquid chromatography. Hypoosmotic stress
      resulted in marked percentage increases in perfusate taurine, aspartate and
      glutamate levels, smaller increases in phosphoethanolamine, glycine and alanine
      and non-significant increases in serine and glutamine. Amino acid levels declined
      during reperfusion with isosmotic perfusate. The anion channel blocker 4
      acetamido-4-isothiocyanostilbene-2:2'-disulfonic acid (SITS, 500 microM)
      significantly reduced hypoosmotic release of taurine, aspartate, glutamate and
      glycine. Furosemide reduced hypoosmotically-evoked releases of taurine, glycine,
      alanine and phosphoethanolamine. The polyunsaturated amino acids, arachidonic and
      linoleic also reduced amino acid efflux. Phospholipase A2 inhibition with 7,7
      dimethyleicosadienoic acid (DEDA, 2 microM) reduced osmotically-evoked releases
      of taurine, aspartate and glutamate. 4-Bromophenacyl bromide (1 microM) inhibited
      osmotically-evoked release of glutamate and glycine. Combined applications of
      SITS + DEDA markedly reduced osmotically evoked release of all eight amino acids.
      Glutamate and aspartate effluxes were not inhibited by the glutamate transport
      inhibitor dihydrokainic acid (1 mM). These results indicate that the hypoosmotic
      stress, by inducing cell swelling, can initiate an amino acid efflux as part of a
      regulatory volume decrease. An opening of anion-permeant channels and
      phospholipase activation appear to be involved in the regulatory volume decrease
      phenomenon.

PMID- 9543250
TI  - The effect of arachidonic acid and free fatty acids on vesicular uptake of
      glutamate and gamma-aminobutyric acid.
AB  - The manner in which arachidonic acid and other free fatty acids influence the
      vesicular uptake of glutamate and gamma-aminobutyric acid (GABA) has been
      investigated. The cis-polyunsaturated fatty acid arachidonic acid (20:4),
      eicosapentanoic acid (20:5) and linolenic acid (18:3) at 150 nmol/mg protein (50
      microM) inhibited the vesicular uptake of glutamate and GABA more than 70%.
      Reduced inhibition of vesicular uptake was seen with the cis-monounsaturated
      fatty acid oleic acid (18:1) and the trans-mono-unsaturated fatty acid elaidic
      acid (18:1). The saturated fatty acids stearic acid (16:0) and arachidic acid
      (20:0) had no significant effect on the uptake. The inhibition of vesicular
      uptake by arachidonic acid was prevented by the addition of fatty acid free
      bovine serum albumin. Arachidonic acid inhibited in a dose-dependent manner the
      generation of the transmembrane pH gradient of the synaptic vesicles. This
      inhibition was proportional to the inhibition of the vesicular uptake of
      glutamate and GABA. The saturated fatty acid arachidic acid showed no inhibition
      of delta pH generation. Arachidonic acid at 200 nmol/mg of protein did not
      increase the uptake-independent leakage of glutamate and GABA from the vesicles,
      showing that the effect of arachidonic acid is not caused by an unspecific
      detergent effect. These results suggest that arachidonic acid and other
      polyunsaturated fatty acids are acting like proton-ionophores on the vesicular
      uptake of these neurotransmitters. This finding may have implications for the
      increased fatty acid concentration during pathological conditions like ischemia
      and in long term potentiation.

PMID- 9543251
TI  - Adenosine modulates cell proliferation in human colonic adenocarcinoma. I.
      Possible involvement of adenosine A1 receptor subtypes in HT29 cells.
AB  - Several lines of evidence suggest that extracellular adenosine interacting with
      specific cell surface receptors may influence cell growth and differentiation of
      cancer cells in culture. The data presented here demonstrate that various
      treatments of human colonic adenocarcinoma HT29 cells in the presence of
      exogenously added adenosine deaminase, which converts extracellular adenosine
      into inosine, resulted in a significant decrease of the proliferation. Cell
      growth inhibition was also observed in the presence of adenosine A1 receptor
      antagonists. These various treatments also induced a significant elevation of
      basal intracellular cAMP levels. This strongly indicated that extracellular
      adenosine was maintaining low intracellular cAMP levels in HT29 cells. A partial
      pharmacological characterization of the binding of the adenosine A1 receptor
      agonist [3H]CCPA (2-chloro-N6-cyclopentyl[2,3,4,5-(3)H]adenosine), and the
      adenosine A1 receptor antagonist [3H]DPCPX (cyclopentyl-1,3-dipropyl[2,3
      (3)H]xanthine), to HT29 cells is also provided. Together the data support the
      idea that A1-adenosine receptors are expressed in HT29 cells and might mediate
      part of the above described effects of adenosine on cell proliferation.

PMID- 9543252
TI  - Adenosine modulates cell proliferation in human colonic carcinoma. II.
      Differential behavior of HT29, DLD-1, Caco-2 and SW403 cell lines.
AB  - In a previous study, we provided evidence that extracellular adenosine modulates
      growth of the poorly differentiated colonic adenocarcinoma cells HT29 and
      proposed that adenosine A1 receptors might mediate proliferative effects. We now
      extend our investigations to a group of colonic adenocarcinoma cells at different
      stages of enterocytic differentiation. In HT29, DLD-1, Caco-2 and SW403,
      proliferation was decreased in the presence of adenosine deaminase (5 or 10
      U/ml), 5'-N-ethylcarboxamido-adenosine (NECA; 1 microM), xanthine amine congener
      and 8-phenyltheophylline (both at 1 nM or 1 microM). NECA stimulated cAMP
      accumulation in all cell lines except for HT29. In the presence of forskolin
      (adenyl cyclase activator) cAMP accumulation was inhibited at sub-nanomolar
      concentrations of NECA and stimulated at micromolar concentrations in all four
      cell lines. The inhibitory response disappeared in the presence of 50 nM
      cyclopentyladenosine (CPA). The binding of [3H]cyclopentyl-1,3-dipropylxanthine
      and [3H]NECA was also investigated in the four cell lines. Results of
      displacement experiments were consistent with the idea that poorly differentiated
      cells with high proliferation rates (e.g. HT29) express mainly adenosine A
      receptors. In contrast, displacement curves with more differentiated cells
      exhibiting low proliferation rates (e.g. Caco-2, DLD-1, SW403) displayed two
      components. The high-affinity component was no longer seen in competition
      experiments performed in the presence of [3H]NECA and 50 nM CPA. Together, our
      results further support the idea that extracellular adenosine stimulates cell
      proliferation in colonic adenocarcinoma cells. The effects might involve cAMP
      coupled adenosine receptors.

PMID- 9543253
TI  - Corticosteroids inhibit the expression of the vascular endothelial growth factor
      gene in human vascular smooth muscle cells.
AB  - The vascular endothelial growth factor (VEGF) is a specific mitogen for vascular
      endothelial cells and enhances vascular permeability and edemagenesis. VEGF is
      also a major regulator of angiogenesis and may be a key target for inhibiting
      angiogenesis in angiogenesis-associated diseases. Among the extensively studied
      angiostatic compounds are several corticosteroids when used alone or in
      combination with heparin. In this study we present evidence for an additional
      mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting
      edemagenesis or angiogenesis. In cultures of aortic human vascular smooth muscle
      cells these corticosteroids (1 x 10(-8) to 1 x 10(-12) M) abolished the platelet
      derived growth factor-induced (PDGF) expression of the VEGF gene in a dose
      dependent manner. In contrast, two precursors of corticosteroids,
      desoxycorticosterone or pregnenolone, did not affect PDGF-induced VEGF
      expression. Our findings indicate that the capacity of corticosteroids to reduce
      edema or to prevent new blood vessel formation may be attributed, at least in
      part to the ability of these agents to abolish the expression of VEGF.

PMID- 9543254
TI  - Suppression of phospholipase C blocks Gi-mediated inhibition of adenylyl cyclase
      activity.
AB  - The potential effect of inhibition of phospholipase C on the response of Gi
      coupled receptors was investigated in neuroblastoma x glioma hybrid (NG108-15)
      cells. The phospholipase C specific inhibitor 1-[6-((17beta-3-methoxyestra
      1,3,5(10)-trien-17-yl)amino)hexyl]-1H -pyrrole-2,5-dione (U73122), which did not
      affect basal and forskolin-stimulated adenylyl cyclase activities, time- and dose
      dependently blocked delta-opioid receptor-mediated inhibition of adenylyl cyclase
      activity, the EC50 (0.5 microM) of which was consistent with that for inhibition
      of bradykinin-dependent phospholipase C activation (EC50 = 1 microM). U73122
      treatment also blocked functional responses of m4 muscarinic receptor and alpha2
      adrenoceptor in NG108-15 cells and three opioid receptors (mu, delta and opioid
      receptor-like receptor (ORL1)) in human neuroblastoma SK-N-SH cells. 1-[6
      ((17Beta-3-Methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-2, 5-pyrrolidinedione
      (U73343), an inactive analog of U73122, did not show any effect, which suggests
      that the blockade by U73122 of Gi-coupled receptor-mediated signaling is probably
      mediated through inhibition of phospholipase C, although a possible direct
      modification of G proteins can not be excluded. Furthermore, treatment with
      U73122 but not U73343 blocked the GTP-induced inhibition of adenylyl cyclase,
      indicating blockade at the level of Gi proteins.

PMID- 9543255
TI  - Synergy of CD95 ligand and teniposide: no role of cleavable complex formation and
      enhanced CD95 expression.
AB  - Teniposide (VM26) enhanced the anti-glioma activity of the cytotoxic cytokine,
      CD95 ligand. Synergy was observed at concentrations of teniposide that were
      insufficient for cleavable DNA topoisomerase II complex formation. CD95 ligand
      did not modulate the formation or removal of such complexes after teniposide
      treatment. These processes were also unaffected by ectopic expression of bcl-2.
      Teniposide enhanced CD95 expression in a glioma cell line with wild-type p53 (LN
      229) but not in two p53 mutant cell lines (T98G, LN-308). Forced expression of a
      transdominant negative p53 mutant prevented the teniposide induced augmentation
      of CD95 expression in LN-229 cells but did not prevent the synergy of CD95 ligand
      and teniposide. Teniposide did not alter CD95 ligand expression, and forced
      expression of CD95 did not modulate sensitivity to VM26. Thus, teniposide-induced
      DNA lesions and alterations in CD95 or CD95 ligand are not necessary for
      teniposide-induced sensitization of human malignant glioma cells to CD95-mediated
      apoptosis.

PMID- 9543256
TI  - Substance P-related inhibitors of mast cell exocytosis act on G-proteins or on
      the cell surface.
AB  - [p-Glu5,D-Trp(7,9,10)]substance P-(5-11) inhibited mastoparan-stimulated GTPase
      activity in homogenized rat peritoneal mast cells and decreased histamine
      secretion induced by mastoparan from streptolysin O-permeabilized mast cells
      (IC50 of about 30 microM), but not from intact cells. In contrast, [D-Pro4,D
      Trp(7,9,10)]substance P-(4-11) inhibited the secretion from intact cells (IC50 of
      about 10 microM) but had no effect on histamine secretion from permeabilized
      cells, suggesting that this peptide exerts its inhibitory effect on the plasma
      membrane, whereas [p-Glu5,D-Trp(7,9,10)]substance P-(5-11) interacts with G
      proteins. Pretreatment of mast cells with neuraminidase led to an inhibition of
      the secretory response to mastoparan and related triggers. This response was
      restored following cell permeabilization, demonstrating the role of the cell
      surface on the entry of mastoparan and related triggers and on their ability to
      reach G proteins sensitive to pertussis toxin and [p-Glu5,D-Trp(7,9,10)]substance
      P-(5-11).

PMID- 9543257
TI  - Signal transduction in cardiac and vascular tissue from normotensive and
      transgenic hypertensive TGR(mREN2)27 rats.
AB  - Adenylyl cyclase and soluble guanylyl cyclase activities were measured in cardiac
      and aortic tissue from transgenic hypertensive TGR(mREN2)27 and normotensive
      Sprague-Dawley rats. Cardiac basal and stimulated adenylyl cyclase activity was
      significantly lower in TGR(mREN2)27 than in Sprague-Dawley rats except after
      uncoupling of G-proteins by Mn2+-ions. Aortic cAMP formation did not differ
      between both strains, indicating that the disturbance of cardiac adenylyl cyclase
      activity was due to local rather than systemic factors. Vascular cGMP formation
      was significantly reduced in TGR(mREN2)27 aortae under basal conditions and after
      stimulation with sodium nitroprusside, indicating that there is a subsensitive
      vasodilating second messenger pathway in the transgenic strain.

PMID- 9543258
TI  - Cyclopiazonic acid and thapsigargin induce platelet aggregation resulting from
      Ca2+ influx through Ca2+ store-activated Ca2+-channels.
AB  - The effects of cyclopiazonic acid and thapsigargin, selective inhibitors of the
      endoplasmic reticulum Ca2+-ATPase pump, on the platelet aggregation were
      investigated using washed rat platelets prepared by chromatography on Sepharose
      2B columns. In Ca2+-free medium, cyclopiazonic acid and thapsigargin did not
      induce aggregation, but in the presence of 1 mM Ca2+, platelet aggregation was
      induced in a concentration-dependent manner. Cyclopiazonic acid- and thapsigargin
      induced platelet aggregation was blocked by 1 mM Ni2+ but not by 100 microM
      indomethacin or 1 microM nifedipine. In aequorin-loaded platelets, cyclopiazonic
      acid and thapsigargin caused sustained elevation of the cytosolic Ca2+
      concentration, an effect which was blocked by Ni2+, a non-selective Ca2+ channel
      blocker and SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenyl]-1H
      imidazole hydrochloride), a putative receptor-operated Ca2+ channel antagonist.
      The above results indicated that both cyclopiazonic acid and thapsigargin induced
      platelet aggregation and elevation of cytosolic Ca2+ concentration, that
      extracellular Ca2+ was essential for cyclopiazonic acid- and thapsigargin-induced
      platelet aggregation, and that platelet aggregation may be associated with Ca2+
      influx through Ca2+ store-activated Ca2+ channels.

PMID- 9543259
TI  - Stereoselective actions of halothane at GABA(A) receptors.
AB  - Isoflurane anesthesia exhibits stereoselectivity, and a corresponding
      stereoselectivity ((+)->(-)-isomer) has been reported at GABA(A) receptors in
      vitro. The objective of the present study was to determine if the positive
      modulatory actions of halothane at GABA(A) receptors exhibited a similar
      stereoselectivity. Both (R)- and (S)-halothane ((+)- and (-)- isomers,
      respectively) enhanced [3H]flunitrazepam binding to brain membranes in a
      concentration dependent manner without a significant difference in either potency
      (EC50) or efficacy (Emax). While both (R)- and (S)-halothane enhanced
      [3H]muscimol binding, the potency of the (+)-isomer was slightly greater than the
      corresponding (-)-isomer (0.91 +/- 0.17 versus 1.45 +/- 0.04% atmospheres,
      respectively (P < 0.02)). Thus, subtle structural differences between
      inhalational anesthetics can have a significant impact on the degree of
      stereoselectivity at the receptor level and may provide insights for the
      development of more specific drugs.

PMID- 9543260
TI  - Upregulation of NMDA receptor subunit proteins in the cerebral cortex during
      diazepam withdrawal.
AB  - The present study investigated the changes in NMDA receptor subunit proteins in
      diazepam-withdrawn rat cerebral cortex, using Western blotting analysis. The
      protein levels of the NR1 and NR2B, but not NR2A, subunits were significantly
      increased in diazepam-withdrawn rats compared to those in control rats.
      Therefore, an increase in the NR1 and NR2B subunit proteins may be responsible
      for both the previously observed upregulation of [3H]dizocilpine binding in the
      cerebral cortex and the appearance of diazepam withdrawal signs.

PMID- 9543261
TI  - Augmented chemosensitivity to hypercapnia: another link in our understanding of
      the pathogenesis of Cheyne-Stokes respiration.

PMID- 9543262
TI  - Testing health status ("quality of life") questionnaires for asthma and COPD.

PMID- 9543263
TI  - Ventilatory control in patients with sleep apnoea and left ventricular
      dysfunction: comparison of obstructive and central sleep apnoea.
AB  - Sleep apnoea is common in patients with heart failure. While most patients have
      central sleep apnoea (CSA), a minority have obstructive sleep apnoea (OSA). The
      pathophysiology of CSA is not well understood. We hypothesized that central
      chemosensitivity would be an important pathophysiological factor in patients with
      CSA, and not in OSA. The aim of this study was to compare ventilatory responses
      between patients with CSA and those with OSA. Acute ventilatory responses to
      eucapnic hypoxia and hyperoxic hypercapnia were measured during wakefulness in 34
      patients (33 males and one female, aged 59+/-8 yrs (mean+/-SD)), with stable
      medically-treated left ventricular dysfunction (LVD) and sleep apnoea (18 OSA and
      16 CSA). Patients with CSA had a decreased awake end-tidal carbon dioxide tension
      (4.1+/-0.5 kPa), increased ventilatory response to carbon dioxide (0.65+/-0.43
      L.min.(-1).kPa PCO2(-1)), and eucapnic hypoxic responses in the normal range
      (0.6+/-0.4 L.min(-1)/% fall in arterial oxygen saturation (Sa,O2)). In contrast,
      patients with OSA had normal end-tidal carbon dioxide tension (4.9+/-0.5 kPa),
      and normal ventilatory responses to hypercapnia (0.29+/-0.16 L.min(-1).kPa PCO2(
      1)) and hypoxia (0.5+/-0.5 L-min(-1)/% fall in Sa,O2). These findings suggest
      that augmented chemosensitivity to hypercapnia may be an important factor in the
      pathophysiology of central sleep apnoea in patients with heart failure.

PMID- 9543264
TI  - Obstructive sleep apnoea and diabetes mellitus: the role of cardiovascular
      autonomic neuropathy.
AB  - Knowledge of conditions associated with an increased prevalence of obstructive
      sleep apnoea (OSA) may help to identify patients with OSA and might give some
      insight into the pathogenesis of OSA and its sequelae. A number of earlier,
      smaller studies hinted at an association between diabetic cardiovascular
      autonomic neuropathy (AN) and OSA. The present study was, therefore, conducted
      with the aim of establishing the prevalence of OSA in diabetics with AN and of
      determining whether OSA is more prevalent in diabetics with AN, than in those
      without. We studied two groups of diabetic patients: 23 with and 25 without AN.
      All patients were evaluated for possible OSA (apnoea/hypopnoea index > or = 10)
      using initial ambulatory screening followed by polysomnography. Six patients with
      AN (26%) were found to have OSA, but none of the patients without AN met the
      diagnostic criteria (p<0.01). When the patients with OSA were compared to those
      without, no differences were found in terms of age, sex, body mass index or
      diabetes type or duration. In conclusion, about one in four diabetic patients
      with autonomic neuropathy suffers from OSA. Thus, obstructive sleep apnoea is
      more prevalent in diabetic patients with autonomic neuropathy, than in those
      without.

PMID- 9543265
TI  - Cardiorespiratory consequences of sleep apnoea syndrome in patients with massive
      obesity.
AB  - Assessment of cardiorespiratory consequences of sleep apnoea syndrome (SAS) is
      difficult owing to confounding factors, especially obesity, that are strongly
      associated with SAS. This study was designed to assess the cardiorespiratory
      consequences of SAS by comparing the results of a comprehensive cardiorespiratory
      evaluation in apnoeic and nonapnoeic patients with massive obesity. In a
      retrospective chart-review study, we studied 60 patients with massive obesity
      defined by a body mass index (BMI) >40 kg.m(-2), presenting no chronic
      respiratory disease, who underwent an extensive assessment of cardiorespiratory
      consequences of obesity, including overnight polysomnography, lung function
      tests, arterial blood gas analysis, evaluation of vascular risk factors,
      myocardial scintigraphy with dipyridamole stress-test, isotopic ventriculography,
      Doppler echocardiography and Holter electrocardiogram recording. SAS defined by
      an apnoea + hypopnoea index (AHI) > or = 10 was diagnosed in 42% of patients (25
      out of 60). Mean+/-SD AHI of SAS-positive (SAS+) patients was 38+/-24. Age, BMI,
      ventilatory function parameters, prevalence of smoking history and diabetes
      mellitus did not differ significantly in SAS+ versus SAS-negative (SAS-) groups.
      The following complications were observed more frequently in SAS+ than in SAS-
      patients: daytime hypoxaemia (35 vs 9%, p<0.02), pulmonary arterial hypertension
      (36 vs 7%, p<0.05) and increased interventricular septal thickness (50 vs 15%,
      p<0.03). No association was found between SAS on the one hand and systemic
      arterial hypertension, coronary artery disease, left ventricular dysfunction and
      nocturnal cardiac arrhythmias on the other. Nocturnal apnoeas in massive obesity
      may thus be associated with moderate daytime hypoxaemia, mild pulmonary arterial
      hypertension and moderate left ventricular hypertrophy, but not with severe
      cardiorespiratory complications.

PMID- 9543266
TI  - Effect of inspiratory muscle training with an intermediate load on inspiratory
      power output in COPD.
AB  - There is very little information about the effect of inspiratory muscle training
      on inspiratory flow (V'I) and thus on power output (PO) in patients with chronic
      obstructive pulmonary disease (COPD). In this study we aimed to evaluate the
      changes induced by training on the determinants of PO. Thirty one patients with
      severe COPD were randomly divided into: Group 1, trained with 30% maximal
      inspiratory pressure (PI,max); Group 2, with 10% PI,max; and Group 3 also trained
      with 30% PI,max, but the breathing pattern was evaluated while performing the
      training manoeuvres along inspiratory muscle training (IMT). All groups used a
      threshold device for 10 weeks. The PO for each of the loads during an incremental
      threshold test was evaluated prior to and after training. Maximal PO (POmax)
      increased in all groups, but the increment was higher in groups trained with 30%
      PI,max (p<0.005), mainly due to an increase in V'I. Group 3 showed a progressive
      increase in V'I (p<0.001) during the training manoeuvres in spite of an increase
      in load along IMT. In addition, the load after IMT was overcome with a shorter
      inspiratory time (tI) (p<0.02), a smaller tI/total duration of the respiratory
      cycle (t(tot)), (p<0.001) with no change in tidal volume or t(tot). The increment
      in POmax in this group correlated with the V'I generated while training (r=0.85;
      p<0.0001). We conclude that in patients with chronic obstructive pulmonary
      disease, the use of an intermediate threshold load for training improves power
      output mainly by increasing inspiratory flow, an effect consistent with an
      increase in shortening velocity of inspiratory muscles.

PMID- 9543267
TI  - Mask intermittent positive pressure ventilation in chronic hypercapnic
      respiratory failure due to chronic obstructive pulmonary disease.
AB  - Noninvasive ventilation in chronic obstructive pulmonary disease (COPD) has been
      shown to improve arterial blood gases but its long-term role has not been
      established. We retrospectively studied 26 consecutive patients with hypercapnic
      ventilatory failure due to COPD in whom oxygen therapy caused worsening
      hypercapnia (defined as a rise in the daytime arterial carbon dioxide tension
      (Pa,CO2) to >8.0 kPa or nocturnal transcutaneous carbon dioxide tension (Ptc,CO2)
      to >9 kPa). All were treated with mask ventilation (15 with nasal and 11 face
      masks) at night and during daytime naps. Additional oxygen therapy was required
      in 15 patients. The mean annualized death rate was 10.8% with a 1 and 3 yr
      survival of 92 and 68%, respectively. After 1 yr the median daytime Pa,CO2 had
      fallen by 1.35 kPa and the arterial oxygen tension (Pa,O2) had risen by 2.4 kPa.
      In subjects not using additional oxygen the median overnight Sa,O2 rose by 12%
      and the Ptc,CO2 fell by 2.8 kPa after 1 yr. The haematocrit was significantly
      less than pretreatment at 6 months and 1 yr. Quality of life in the domain of
      role limitation by physical health (measured using the SF-36 questionnaire)
      improved significantly at 6 months. Survival in this selected group with
      clinically stable airflow obstruction unable to tolerate oxygen therapy and
      treated with noninvasive mask ventilation is better than historical controls and
      is comparable to those able to tolerate oxygen therapy. Poor survival was
      associated with a low forced expiratory volume in one second, a low body mass
      index and a high nocturnal transcutaneous carbon dioxide tension. No difference
      in survival was found between those treated with mask intermittent positive
      pressure ventilation alone or with mask intermittent positive pressure and
      supplementary oxygen therapy.

PMID- 9543268
TI  - Testosterone levels in men with chronic obstructive pulmonary disease with or
      without glucocorticoid therapy.
AB  - Under the clinical impression that patients with chronic obstructive pulmonary
      disease (COPD) may demonstrate signs compatible with hypogonadism, we
      investigated whether oral glucocorticoid therapy is associated with testosterone
      deficiency. Thirty six men with COPD of whom 16 were receiving oral
      glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were
      investigated in a cross-sectional cohort study. Patients with or without oral
      glucocorticoid therapy were not different in terms of age, smoking history and
      additional therapy. Vital capacity, forced expiratory volume in one second,
      airway resistance, intrathoracic gas volume and blood gases at rest were not
      different between the groups. However, patients receiving glucocorticoids had a
      shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02)
      compared to patients without oral steroid therapy. Serum levels of testosterone
      (mean+/-SEM 13.7+/-0.9) were below normal (<12 nM) in 15 of 36 patients. Serum
      testosterone did not correlate with any other evaluated parameter. Serum levels
      of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of
      the 36 patients, including all patients receiving glucocorticoid treatment. In
      the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the
      current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index
      (r=0.241; p=0.037). All other parameters examined revealed no significant
      correlations in multiple regression analysis. Glucocorticoid treatment appears to
      aggravate hypogonadism and a therapeutic study using testosterone in patients
      with chronic obstructive pulmonary disease receiving glucocorticoid medication
      appears warranted.

PMID- 9543269
TI  - Immunological findings in blood and bronchoalveolar lavage fluid in chronic
      bronchitis patients with recurrent infectious exacerbations.
AB  - Bronchial infections are common in smokers and seem to be related to the presence
      of chronic bronchitis (CB). Why only some smokers develop repeated bronchial
      infections is not known. The aim of this study was to screen for immunological
      changes associated with disease in patients with CB and recurrent infectious
      exacerbations compared to asymptomatic smokers. Sixteen smokers with stable CB
      and recurrent infectious exacerbations, and 18 asymptomatic smokers, all without
      any immunomodulating treatment, underwent bronchoscopy and bronchoalveolar lavage
      (BAL). Smoking history and current smoking status were comparable. Serum levels
      of immunoglobulin (Ig)A, IgM, IgG and IgG subclasses were measured. Blood and BAL
      lymphocyte phenotypes and proliferative responses of peripheral blood mononuclear
      cells (PBMCs) to various stimulators were analysed. Unstimulated and tetanus
      toxoid-stimulated production of cytokines in PBMC cultures was measured. Natural
      killer (NK-) cell activity was analysed. A significantly (p<0.05) lower level of
      IgG3 was found in the CB group, and a significantly (p<0.01) higher proliferative
      response of PBMCs was found in the CB group after stimulation with diphtheria
      toxoid. Detectable levels of interleukin (IL)-6, tumour necrosis factor-alpha
      (TNF-alpha) and interferon-gamma, but not of IL-2, IL-4 or transforming growth
      factor-beta2, were found in supernatants from cultured cells in both study
      groups. Stimulated TNF-alpha production was significantly (p<0.05) higher in the
      CB group. NK-cell activity did not differ significantly between the study groups.
      There were no major differences between the groups in lymphocyte subpopulations
      in blood or BAL. In conclusion, no major alterations in the analysed indices of
      cell-mediated and humoral immunity were found in patients with chronic bronchitis
      prone to recurrent infectious exacerbations when compared with asymptomatic
      smoking controls.

PMID- 9543270
TI  - Quality of life in patients with chronic respiratory disease: the Spanish version
      of the Chronic Respiratory Questionnaire (CRQ)
AB  - The aim of this study was to translate the Chronic Respiratory Questionnaire
      (CRQ) into Spanish and to test its measurement properties. The study was
      performed in 60 patients with chronic obstructive pulmonary disease (forced
      expiratory volume in one second (FEV1) mean+/-SD 35+/-14% of reference value). A
      rigorous process of forward and back translation and review produced an easily
      comprehensible questionnaire, which was administered together with measures of
      pulmonary function and exercise capacity. The patients were randomly allocated to
      one of two groups: 30 received respiratory rehabilitation and the other 30
      received standard community care only. Weak to moderate statistically significant
      correlations (0.2-0.38) were found between the domains of the CRQ and pulmonary
      function and exercise measures. For the three CRQ domains that measure
      differences between patients at a point in time, Crohnbach's alpha and intraclass
      correlation coefficients were: fatigue 0.80 and 0.80; emotional function 0.86 and
      0.68; and mastery domains 0.84 and 0.67, respectively. Scores remained stable in
      patients who were deemed clinically stable, and showed large statistically
      significant improvement (p<0.0001) in patients in the rehabilitation programme.
      Only low correlations were found between the changes in CRQ and the changes in
      pulmonary function and exercise capacity. The index of responsiveness was 0.92
      for fatigue, and 0.91 for dyspnoea, emotional function and mastery. In
      conclusion, the Spanish translation of the Chronic Respiratory Questionnaire is
      likely to be useful for measuring differences between patients, and particularly
      for measuring the effects of intervention on quality of life in chronic
      respiratory disease.

PMID- 9543271
TI  - Reliability and validity of a Swedish version of the St George's Respiratory
      Questionnaire.
AB  - The St George's Respiratory Questionnaire (SGRQ) was designed to measure quality
      of life (QoL) in obstructive pulmonary disease. Its reliability, validity and
      sensitivity have been demonstrated. The aim was to develop a Swedish version of
      the SGRQ and to confirm its scaling and clinical properties. The SGRQ was adapted
      for Swedish conditions following a translation-backtranslation procedure. The
      psychometric and clinical evaluation included 68 patients with chronic
      obstructive pulmonary disease (COPD). Supplementary QoL, clinical and
      physiological data were collected. A follow-up study was performed 1 yr later.
      Correlation analysis used a multitrait-multimethod model. Internal consistency
      reliability and discriminant validity were documented by performing a multitrait
      analysis. The results confirmed expected levels of associations. Correlation
      coefficients between the SGRQ total score and the Sickness Impact Profile Total
      score (a generic health measure), forced expiratory volume in one second (FEV1)
      and 6 min walking distance were 0.69, -0.42 and -0.61 respectively. The pattern
      of correlations in the Swedish data set was very similar to that of the original.
      The stability of the SGRQ scores was confirmed at follow-up after 1 yr. The
      reliability was satisfactory, with Cronbach's alpha coefficients >0.80 for the
      SGRQ and its subdimensions. In conclusion, the Swedish version of the St George's
      Respiratory Questionnaire is reliable, valid and compares well with the
      corresponding tests of the original version.

PMID- 9543272
TI  - Association between health-related quality of life and consultation for
      respiratory symptoms: results from the DIMCA programme.
AB  - In general practice, diagnosis of chronic obstructive pulmonary disease (COPD) is
      hampered by underpresentation. A substantial proportion of subjects experiencing
      respiratory complaints do not consult their general practitioner (GP). In this
      study, the relationship between disease-specific quality of life and presentation
      of respiratory symptoms to a GP is investigated. A random sample from the general
      population (undiagnosed subjects) was screened for symptoms and objective signs
      of COPD (n=1,155). The lung function of subjects with symptoms of COPD was
      monitored for 6 months. During this period, 48 new COPD patients with a
      persistently reduced lung function (forced expiratory volume in one second (FEV1)
      less than or equal to the predicted value minus 2 SD) were detected. A disease
      specific quality-of-life questionnaire (chronic respiratory questionnaire (CRQ))
      was administered and clinical and GP consultation data were collected.
      Multivariate analysis showed that quality-of-life impairments due to dyspnoea and
      fatigue and variability in lung function (bronchial hyperresponsiveness,
      reversibility and peak expiratory flow rate variability) were related to medical
      consultation. Only 31% of the newly detected patients reported that they had ever
      visited their GP for respiratory complaints. A similarly low percentage was found
      in the rest of the sample (26%). It is concluded that the mere presence of
      respiratory symptoms or a (gradually) reduced lung function is insufficient
      reason for patients to seek medical help. Subjects are more likely to consult
      their general practitioner once their quality of everyday life is affected or
      they experience variability in lung function.

PMID- 9543273
TI  - Empirical therapy for nonhospitalized patients with community-acquired pneumonia.
      Study Group of General Practitioners.
AB  - A prospective survey involving a group of 95 general practitioners (GPs) in
      France was conducted to describe antibiotic therapy prescribed for out-patients
      with community-acquired pneumonia (CAP). A total of 173 cases of CAP, defined by
      the association of fever and pulmonary focal crackles and/or radiological changes
      consistent with a pulmonary infection, were reported between February 1993 and
      March 1994: 84 males and 89 females (mean age: 48 yrs) of whom 45% had no
      underlying disease. Nineteen (11%) were immediately hospitalized and the
      remaining 154 out-patients were treated without microbiological investigation.
      First-line antibiotic therapy was amoxicillin or amoxicillin-clavulanic acid
      combination (57%), a first or second generation cephalosporin (12%), ceftriaxone
      (8%), oral broad-spectrum cephalosporin (3%), a macrolide (16%), a tetracycline
      (1%) and a fluoroquinolone (2%). A total of 120 (78%) patients recovered with no
      change in treatment and 34 (22%) patients failed to improve: 18 were hospitalized
      and 16 had a second-line therapy, mainly a macrolide or a quinolone. Five
      patients died at hospital. The overall mortality was 3%, and 14% in hospitalized
      patients. Empirical therapy using a betalactam to target a presumed pneumococcal
      infection, in agreement with European guidelines, is appropriate for out-patients
      with mild lobar community-acquired pneumonia.

PMID- 9543274
TI  - Distribution of immunoreactive endothelin in the lungs of mice during respiratory
      viral infection.
AB  - Respiratory tract viral infections are associated with the generation of a wide
      array of pro-inflammatory cytokines, some of which enhance the release of the
      potent airway smooth muscle spasmogen, endothelin, from respiratory epithelial
      cells in tissue culture. The aim of this study was to determine whether the
      content and distribution of immunoreactive endothelin in the intact murine lung
      is increased during the course of a respiratory tract viral infection. Mice were
      inoculated intranasally with Influenza A/PR-8/34 virus or sterile vehicle and at
      various days postinoculation were sacrificed, and their lungs processed for
      either fluorescence immunohistochemistry with rabbit anti-endothelin sera or
      measurement of immunoreactive endothelin with an enzyme-linked immunosorbent
      assay (ELISA). At 2 and 4 days postinoculation, the content of immunoreactive
      endothelin in lung extracts of virus-infected mice was approximately twice that
      present in lung extracts from control mice (n=3-4, p<0.05). Consistent with this,
      an increased intensity and broader distribution of fluorescent
      immunohistochemical staining for endothelin was observed in the airway epithelium
      of the trachea and intrapulmonary airways of virus-infected mice. This study has
      clearly demonstrated that respiratory tract viral infection is associated with an
      increased content and broader distribution of immunoreactive endothelin within
      the lungs of mice. Whether the elevated content of endothelin contributes to the
      symptoms of virus-induced hyperresponsiveness or to virus-induced exacerbations
      of asthma remains to be established.

PMID- 9543275
TI  - Effect of salmeterol on Haemophilus influenzae infection of respiratory mucosa in
      vitro.
AB  - Haemophilus influenzae is a common bacterial pathogen causing human respiratory
      tract infections. We have previously shown that the beta2-agonist salmeterol
      reduces damage to the respiratory mucosa caused by Pseudomonas aeruginosa in
      vitro. We have now investigated the effect of salmeterol on H. influenzae
      infection of adenoid tissue in an organ culture by scanning electron microscopy.
      Tissue was preincubated with or without salmeterol (4x10(-7)M), prior to
      infection with H. influenzae and incubated for 12 or 24 h. Infected organ
      cultures had increased epithelial damage and decreased numbers of both ciliated
      and unciliated cells at 12h, which were significantly different (p < or = 0.01)
      from the controls at 24 h. Salmeterol (4x10(-7)M) significantly (p < or = 0.03)
      reduced damage and loss of ciliated cells in infected organ cultures at both 12
      and 24, and significantly (p < or = 0.03) reduced loss of unciliated cells at 24
      h. Salmeterol had no effect on the density of bacteria adhering to each
      individual mucosal feature or the total number of bacteria adhering to the organ
      culture. These results suggest that salmeterol protects the respiratory
      epithelium against Haemophilus influenzae-induced damage. The mechanism of
      salmeterol cytoprotection and its potential clinical relevance remain to be
      investigated.

PMID- 9543276
TI  - Adhesion molecule expression in the lung: a comparison between normal and diffuse
      interstitial lung disease.
AB  - Cellular adhesion molecules are crucial determinants of the migration of immune
      effector cells to the tissues. In chronic inflammatory diseases, upregulation of
      the expression of these molecules may contribute to the persistent inflammatory
      process. The aim of this study was to determine whether there is evidence of
      adhesion molecule expression in chronically inflamed lung. Soluble adhesion
      molecules in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked
      immunoassay in 54 patients with chronic interstitial lung diseases and 16 normal
      controls. Adhesion molecule expression in fibrosing alveolitis (FA) lung and in
      control lung was assessed using immunohistology and reverse transcription
      polymerase chain reaction (RT-PCR) amplification. Soluble intercellular adhesion
      molecule-1 (ICAM-1) was detected in all but two subjects. There was no difference
      in ICAM-1 concentration between disease groups and normal subjects. In contrast,
      soluble E-selectin was detected in 17 of the 70 subjects and was significantly
      associated with the presence of lung disease (p=0.0173). Furthermore, the
      presence of soluble E-selectin was associated with a raised lymphocyte percentage
      in BALF (p=0.0069). Soluble VCAM was only detected in five of the 70 subjects
      (two normals, three patients). There was no difference in adhesion molecule
      expression in lung parenchyma between FA and controls assessed by immunohistology
      and RT-PCR. The most striking finding of our study was the universal expression
      of intercellular adhesion molecule-1 in both normal and diseased lung,
      emphasizing the important role of the lung in immune function. Upregulation of E
      selectin may contribute to inflammatory cell accumulation in chronic interstitial
      lung diseases.

PMID- 9543277
TI  - Changing strategies of lung biopsies in diffuse lung diseases: the impact of
      video-assisted thoracoscopy.
AB  - The aims of this report were: 1) to compare the strategy of bioptic approach in
      Italy during the last 4 yrs with a previous period; and 2) to compare efficacy
      and safety of video-assisted thorascopic lung biopsy (VTLB) versus OLB. We
      retrospectively evaluated: 1) the strategy of the bioptic approach in the Milan
      Sarcoid Clinic in the years 1992-1995 (201 patients) versus 1988-1991 (197
      patients); and 2) data from 65 VTLB procedures in the years 1992-1995 versus 68
      OLB procedures in the years 1988-1991 performed in patients with diffuse lung
      disease. It was found that the use of OLB (17-9%), mediastinoscopy (15-5%), and
      scalene node biopsy (20-7%) decreased, whereas transbronchial biopsy (TBB)
      increased (11-17%). VTLB biopsy is now performed in 17% of patients. VTLB
      compares favourably with OLB as there is less need for analgesia (7.5+/-7.5
      versus 17.5+/-8.0 methadone mg i.m.: p<0.001), lower blood loss (61+/-58 versus
      156+/-84 mL in the first postoperative day: p<0.001), and shorter postoperative
      stay (4.7+/-1.6 versus 5.7+/-1.4 days: p<0.001). Specimen adequacy (98.6 versus
      985%) and diagnostic accuracy (86.1% VTLB, versus 92.6% OLB: p>0.05) were the
      same in the two groups. In conclusion, video-assisted thoracoscopic lung biopsy
      is replacing both mediastinoscopy and open lung biopsy. It is at present the best
      option when a surgical procedure is required for histological confirmation of
      diffuse lung disease.

PMID- 9543278
TI  - Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse
      panbronchiolitis.
AB  - Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides
      in the azurophil granules, which belong to a family of mammalian neutrophil
      peptides named defensins. Here we investigate the role of these peptides in
      diffuse panbronchiolitis (DPB). Defensins (human neutrophil peptide-1, -2 and -3)
      were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30
      patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15
      healthy adults. The concentration of defensins was higher in BALF of patients
      with DPB than in patients with IPF and healthy subjects. DPB and IPF patients
      also had significantly higher plasma concentrations of defensins than controls.
      In patients with DPB, BALF concentration of defensins correlated significantly
      with neutrophil count or BALF concentration of interleukin (IL)-8.
      Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed
      localization of defensins in neutrophils and mucinous exudate in the airways, and
      on the surface of bronchiolar epithelial cells. In vitro studies showed an
      enhanced extracellular release of defensins following stimulation of neutrophils
      with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human
      recombinant IL-8. Treatment of DPB with macrolides for 6 months significantly
      reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our
      results indicate accumulation of neutrophil-derived defensins in the airway in
      diffuse panbronchiolitis, and suggest that defensins may be a marker of
      neutrophil activity in this disease.

PMID- 9543279
TI  - Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of
      inflammatory lung diseases.
AB  - Complement receptor type 1 (CR1) (CD35; C3b/C4b receptor) is a transmembrane
      protein of many haematopoietic cells. Once cleaved, soluble complement receptor
      type 1 (sCR1) exerts opposite effects as a powerful inhibitor of complement. This
      study addressed both the question of whether sCR1 was found in bronchoalveolar
      lavage (BAL) of normals and patients with various inflammatory disease, and its
      possible origin. In this retrospective study covering specimen and clinical data
      of 124 patients with acute and chronic inflammatory lung pathologies, BAL
      supernatants were analysed by enzyme-linked immunosorbent assay technique for
      sCR1. Correlations were made between the sCR1 levels obtained and the
      constituents of BAL. Human alveolar macrophages were cultivated in order to
      determine their secretory capacity of sCR1. Alveolar macrophages from normal
      subjects were shown to release sCR1 in vitro. In addition, sCR1 was present in
      BAL of normal controls and was significantly increased in acute inflammatory lung
      diseases such as acute respiratory distress syndrome (ARDS), bacterial and
      Pneumocystis carinii pneumonia, as well as in chronic inflammatory diseases such
      as interstitial lung fibrosis and sarcoidosis. In BAL of ARDS, bacterial, and P.
      carinii pneumonia, there was a good correlation between sCR1 and the absolute
      neutrophil counts. In sarcoidosis, a correlation was found with BAL lymphocyte
      counts. Serum sCR1 was not increased in patients compared to controls. Soluble
      complement receptor type 1 (sCR1) is found in the bronchoalveolar lavage in
      health as well as in acute and chronic inflammatory disease. Alveolar macrophages
      are capable of releasing sCR1 in vitro and may be the main physiological source
      of sCR1 in the alveoli. The good correlation between sCR1 and the absolute
      neutrophil or lymphocyte numbers in bronchoalveolar lavage of inflammatory
      diseases suggests a predominant role of leucocytes for the release of sCR1 in
      such conditions. The release of this inhibitor of complement may be crucial to
      control and reduce complement activation and thus prevent lung injury.

PMID- 9543280
TI  - Neutrophil elastase: alpha-1-proteinase inhibitor complex in serum and
      bronchoalveolar lavage fluid in patients with pulmonary fibrosis.
AB  - It was hypothesized that neutrophil elastase released from activated neutrophils
      may play an important role in the pathogenesis of pulmonary fibrosis. In the
      present study, we measured the neutrophil elastase:alpha-1-proteinase inhibitor
      complex (E-PI) in serum and bronchoalveolar lavage fluid (BALF) in 26 patients
      with pulmonary fibrosis and evaluated the correlation between E-PI levels and
      several parameters. E-PI levels in serum of patients with pulmonary fibrosis
      (635.8+/-112.0 ng.mL(-1)) were significantly elevated compared to normal
      nonsmokers (122.0+/-4.0 ng.mL(-1)) as well as normal smokers (132.8+/-8.4 ng.mL(
      1)) (p<0.01). E-PI levels in serum significantly correlated with hepatocyte
      growth factor (HGF) levels in serum, C-reactive protein (CRP), and negatively
      correlated with arterial oxygen tension (Pa,O2), and arterial carbon dioxide
      tension (Pa,CO2). E-PI/albumin levels in BALF significantly correlated with
      HGF/albumin levels in BALF, lactate dehydrogenase (LDH)/albumin in BALF, total
      number of inflammatory cells (alveolar macrophages and neutrophils) in BALF, and
      several markers derived from epithelial cells in BALF. Our data demonstrated: 1)
      neutrophil elastase:alpha-1-proteinase inhibitor complex in serum increased in
      patients with pulmonary fibrosis; and 2) neutrophil elastase:alpha-1-proteinase
      inhibitor complex in serum and bronchoalveolar lavage fluid correlated with
      clinical parameters in pulmonary fibrosis. These results suggest that neutrophil
      elastase may play a significant role in the process of lung injury in pulmonary
      fibrosis.

PMID- 9543281
TI  - Relationship between exhaled nitric oxide and airway hyperresponsiveness
      following experimental rhinovirus infection in asthmatic subjects.
AB  - Exhaled nitric oxide (NO) is elevated in asthmatics, and varies with disease
      severity. We postulated that a respiratory virus infection increases exhaled NO
      levels in asthma, and examined the relationship between the virus-induced changes
      in exhaled NO and in airway hyperresponsiveness to histamine. In a parallel
      study, seven patients underwent experimental rhinovirus 16 (RV16) inoculation at
      days 0 and 1, whilst seven patients received placebo. Exhaled NO was measured at
      baseline (day 0) and at days 1, 2 and 3 after inoculation. Histamine challenges
      were performed prior to (day -7) and after inoculation (day 3), and were
      expressed as provocative concentration causing a 20% fall in forced expiratory
      volume in one second (FEV1) (PC20). Following RV16 infection there was a
      significant increase in NO at days 2 and 3 as compared to baseline (median change
      (range): 4.2 (7.5) parts per billion (ppb), p=0.03, and 3.0 (10.1) ppb, p=0.02,
      respectively). Furthermore, PC20 decreased significantly following RV16 infection
      (mean+/-SD change in doubling dose: -0.65+/-0.54, p=0.02), whereas PC20 did not
      change in the placebo group (p=0.1). There was a significant correlation between
      the RV16-induced changes in exhaled NO levels at day 2 and the accompanying
      changes in PC20 at day 3 (rank correlation coefficient (rs): 0.86, p=0.01).
      Hence, the greater the increase in exhaled NO, the smaller the decrease in PC20.
      We conclude that rhinovirus infection increases exhaled nitric oxide levels in
      asthmatics, and that this increase is inversely associated with worsening of
      airway hyperresponsiveness to histamine. These results suggest that viral
      induction of nitric oxide synthase within the airways may play a protective role
      in exacerbations of asthma.

PMID- 9543282
TI  - Superoxide anion production by monocytes of corticosteroid-treated asthmatic
      patients.
AB  - Reactive oxygen species play an important role in promoting inflammation. Blood
      monocytes have been described to release higher amounts of superoxide anion in
      uncontrolled and untreated asthmatics. Corticosteroids are widely used in asthma,
      but little is known about their molecular mechanism of action. The aim of our
      study was to analyse the ex vivo effect of corticosteroid treatments on
      superoxide anion release by blood monocytes. Superoxide anion release was
      measured by a spectrophotometric method based on the superoxide dismutase (SOD) 
      inhibitable reduction of ferricytochrome C by blood monocytes from untreated
      patients and asthmatics treated with i.v., inhaled and oral corticosteroids.
      Monocytes from uncontrolled and untreated asthmatics, released high amounts of
      superoxide anions. After short-term treatment with i.v., corticosteroids, this
      release was found to decrease significantly (1.410 versus 0.340 nM, p<0.05).
      Cells from asthmatics who had undergone long-term treatment with inhaled or oral
      steroids presented low amounts of superoxide anion production, with a significant
      difference as compared to untreated asthmatics (0.375 nM p<0.01 and 0.620 nM
      p<0.02 respectively). In general, patients with controlled asthma (treated with
      short-term oral steroids, or with long-term inhaled steroids) released lesser
      amounts of superoxide anion than uncontrolled and untreated asthmatics. In the
      case of steroid-dependent asthmatics there was no difference between patients
      with a controlled or uncontrolled disease.

PMID- 9543283
TI  - Effects of long-term inhaled corticosteroids on skin collagen synthesis and
      thickness in asthmatic patients.
AB  - There are only a few studies on the adverse effects of inhaled corticosteroids on
      the skin in asthmatic patients. Therefore, we evaluated the effect of inhaled
      corticosteroids on de novo collagen synthesis of skin and bone, skin thickness
      and the total amount of skin collagen. Twenty seven consecutive new asthmatic
      patients, on a moderate dose of budesonide or beclomethasone dipropionate, were
      invited to take part in this prospective study. Radioimmunological analyses of
      aminoterminal propeptides of type I and III procollagens (PINP, PIIINP,
      respectively) in suction blister fluid (SBF) of skin and in serum and
      carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carbox
      terminal telopeptide of type I collagen (ICTP) in serum were performed at entry
      and after 3 and 6 months of inhaled corticosteroid treatment. Ultrasound
      measurements of skin thickness at two sites were performed at entry, at 3 and 6
      months and after 1-2 yrs of inhaled corticosteroid treatment in 20 patients, six
      of whom had been prescribed one or more courses of oral corticosteroids. Skin
      hydroxyproline of punch biopsies was determined to measure the total amount of
      skin collagen (males, at entry and at 6 months). Skin thickness and the total
      amount of skin collagen on the abdomen were unchanged after 1-2 yrs of inhaled
      corticosteroid use. A slight decrease was observed in the upper arm skin
      thickness, especially in those subjects who had received inhaled plus oral
      corticosteroids. The procollagen propeptide concentrations (PINP, PIIINP) were
      markedly decreased in SBF at 3 months and remained at this level at 6 months. In
      serum, a slight decrease was seen in the PINP, PIIINP and ICTP concentrations at
      3 and 6 months. In conclusion, inhaled corticosteroids decrease the collagen
      synthesis of skin and bone, but skin thickness and the total amount of collagen
      in skin are not changed markedly after 1-2 yrs of treatment.

PMID- 9543284
TI  - Effects of oral hyposensitization with recombinant Der f2 on immediate airway
      constriction in a murine allergic model.
AB  - Recombinant Der f2 (rDer f2) has recently been developed as a promising allergen
      for the diagnosis and immunotherapy of house-dust mite allergy, and studies in
      immunology. The aim of the present study was to evaluate whether oral
      administration of rDer f2 could suppress an immediate allergic reaction in mice
      sensitized with mite allergen. We developed a murine allergic model that showed
      bronchoconstriction after inhalation of rDer f2, and studied the effect of oral
      administration of rDer f2 on the reaction. Seven week old male A/J mice were
      intranasally immunized with rDer f2 12 times. Sensitized mice showed anti-rDer f2
      immunoglobulin (Ig)E production and immediate airway constriction after
      inhalation of 10 mg.mL(-1) of rDer f2, as determined by the Konzett-Rossler
      method. Immunized animals were divided into three groups, and fed phosphate
      buffered saline (PBS), 0.1 mg.day(-1), or 1 mg.day(-1) of rDer f2 for 4 weeks,
      respectively. Seven days after the last feeding, the mice were examined for their
      immediate response. Animals fed with 1 mg.day(-1) rDer f2 showed significantly
      reduced bronchoconstriction after inhalation of both 2 mg.mL(-1) and 10 mg.mL(-1)
      of rDer f2 compared with PBS-fed mice. Similar results were obtained when we
      examined mice 10 weeks after the last feeding. Reactions in the 0.1 mg.day(-1)
      rDer f2-fed group also tended to decrease in comparison with PBS-fed animals.
      Plasma anti-rDer f2 IgE, IgG1, IgG2a, and IgG2b levels were not changed by
      feeding with rDer f2. We conclude that recombinant Der f2 exhibits both
      sensitizing and hyposensitizing activities in mice. rDer f2 may be useful in
      immunotherapy and diagnosis of house-dust mite allergy.

PMID- 9543285
TI  - Reported food intolerance and respiratory symptoms in young adults.
AB  - The aim of the study was to assess the ability of the European Community
      Respiratory Health Survey (ECRHS) questionnaire to provide data on the
      prevalence, type and reported symptoms associated with food intolerance from a
      group of young adults in Melbourne. Six hundred and sixty nine randomly selected
      subjects completed the questionnaire with 553 attending the laboratory for skin
      prick tests, anthropometry, and ventilatory function tests. A further 207
      symptomatic participants completed the questionnaire, with 204 of them attending
      the laboratory. Seventeen per cent of all respondents reported food intolerance
      or food allergy. A wide variety of food items was cited as being responsible for
      food-related illnesses. Those with current asthma did not report food-related
      illness more frequently than those without asthma. Respondents who reported
      respiratory symptoms following food ingestion were more likely to be atopic, to
      have used inhaled respiratory medications in the previous 12 months, reported
      less exposure to regular passive smoking over the past 12 months and weighed
      more. These associations between respiratory symptoms and food intolerance
      require further prospective investigation and verification. The importance of
      using appropriate dietary methodology in future studies for determining diet
      disease relationships was highlighted by this study.

PMID- 9543286
TI  - Airway dynamics, oesophageal pressure and cough.
AB  - This study hypothesizes that: peak supramaximal airflow during cough reflects
      expiratory muscle effort, and that expiratory muscle function during cough might
      be assessed from the airflow signal alone. We monitored airflow and oesophageal
      pressure (Poes) in normal subjects during cough generated under two conditions:
      1) voluntarily from functional residual capacity (FRC); and 2) involuntarily
      after inhalation of citric acid (CA). Maximal expiratory cough flow was
      quantified as the quotient of maximal flow during a given cough divided by
      maximal flow at the matched volume of thoracic gas (Vtg) as identified on the
      maximal expiratory flow-volume curve. We found: flow ratios correlated poorly
      with Poes; the variance of flow ratios associated with a series of voluntary
      coughs was poorly explained by Poes. During CA inhalation, when the Vtg
      compressed during cough could not be controlled, correlation of Poes with flow
      ratio remained poor. We conclude that to study the motor limb of the cough
      reflex, measurements of both airflow and oesophageal pressure are required.

PMID- 9543287
TI  - High dose rate endobronchial brachytherapy: results and complications in 189
      patients.
AB  - The purpose of this study was to determine the benefit of high dose rate
      endobronchial brachytherapy in the treatment of obstructive lung cancer. Between
      September 1990 and March 1995, 189 patients with bronchogenic carcinoma were
      treated with high dose rate endobronchial brachytherapy. Most patients (69.3%)
      had received prior treatment and presented with symptomatic bronchial obstruction
      due to either recurrent or residual endobronchial disease. A small group (12%)
      was medically unfit for either surgical resection or thoracic radiotherapy and
      benefited from endobronchial brachytherapy alone for small endobronchial tumours.
      The remainder of the patients had not been treated previously and endobronchial
      brachytherapy was performed for life-threatening symptoms requiring emergency
      obstruction relief before other therapy. Treatment was performed weekly and
      consisted of three to four 8 to 10 Gy fractions at a radius of 10 mm from the
      centre of the source. Major symptomatic relief was obtained for haemoptysis
      (74%), dyspnoea (54%), and cough (54%). Complete endoscopic response was observed
      in 54% of cases. Median survival was 7 months for the entire group. For small,
      strictly endobronchial tumours, complete response rate was 96%, median survival
      17 months, and 30 month survival 46%, with a plateau starting at 18 months. Grade
      3 to 4 toxicities occurred at a rate of 17% and included massive haemoptysis
      (n=13), bronchial stenosis (n=12), soft tissue necrosis (n=8), and bronchial
      fistula (n=3). By univariate analysis, no factor was found to be predictive of
      late pulmonary toxicity. The present study confirms the usefulness of
      endobronchial brachytherapy in alleviating symptoms caused by endobronchial
      recurrence of bronchogenic carcinoma. In addition, this therapy can be tried with
      curative intent in patients who present with small endobronchial tumours and are
      not candidates for other forms of therapy.

PMID- 9543288
TI  - Radiographically occult lung cancer treated with fibreoptic bronchoscopic
      electrocautery: a pilot study of a simple and inexpensive technique.
AB  - The curative potential of bronchoscopic intervention, e.g. photodynamic therapy
      (PDT) and brachytherapy, for resectable radiographically occult lung cancer has
      been reported previously. Bronchoscopic electrocautery is currently feasible
      using an insulated flexible bronchoscope to coagulate and vaporize tumour tissue.
      Since the lesions are usually small, noninvasive bronchoscopic electrocautery may
      be able to eradicate radiographically occult lung cancer completely. In a
      prospective study, 13 patients with 15 radiographically occult lung cancer
      lesions were treated with bronchoscopic electrocautery. The duration of follow-up
      was > or = 16 months. The median age of the patients was 69 yrs (range 48-79
      yrs). Fibreoptic bronchoscopy under local anaesthesia was used to coagulate the
      occult lung cancer. Approximately 30 W of energy was applied until visible
      necrosis of the tumour area became apparent. There were no immediate
      complications. In 10 patients with 12 lesions, a complete response (CR) was
      obtained (CR rate 80%; 95% confidence interval (95% CI) 52-96%). Median duration
      of follow-up was 21 months (range 16-43 months). Bronchoscopic electrocautery did
      not obtain a CR in the remaining three patients, but PDT also failed to achieve
      CR. Two patients underwent radical resection, and the tumours were histologically
      confirmed to be more invasive. One patient received external radiotherapy. Three
      patients with a CR died during follow-up, two as a result of myocardial
      infarction and apoplexy, and one because of metastasis from his previously
      resected T3N1 primary large cell cancer. Current data show bronchoscopic
      electrocautery to be equally effective and potentially as curative as
      photodynamic therapy for treating patients with radiographically occult lung
      cancer. Obvious advantages are that it is an inexpensive and simple procedure,
      which does not cause photosensitivity.

PMID- 9543289
TI  - Depressive reactions to lung cancer are common and often followed by a poor
      outcome.
AB  - In diverse human malignancies, including lung cancer, quality of life (QOL)
      affects the clinical outcome of patients. Many QOL dimensions, however, are
      influenced by physical status. The current study was undertaken to delineate the
      role of depression, a state of mind not necessarily influenced by somatic
      factors. All patients, seen for a newly diagnosed carcinoma of the lung, received
      a copy of the Self-rating Depression Scale (SDS) proposed by W.W.K. Zung. One
      hundred and thirty three patients were able and willing to complete the
      questionnaire. A depression index was calculated, as originally described.
      Nineteen other prognostically important variables were recorded and available for
      evaluation. Among the 95 patients who completed all 20 items included in the
      questionnaire, 53 had an SDS index < or = 50 (no depression), while 42 were
      moderately or severely depressed (SDS index >50). The survival of depressed
      patients was significantly lower (p=0.048). Diverse SDS subscales were associated
      with survival, in either univariate or multivariate analysis. SDS item 19, "I
      feel that others would be better off if I were dead", emerged as the most
      significant one. A multivariate model of survival, constructed using only SDS
      data, had a global Chi-squared value of 29.78, and a p-value of 0.00023. Based on
      this evidence, it appears that a relationship does exist between patients'
      depression and prognosis, at least in lung cancer. Further studies are needed to
      clarify the prognostic effect of depression in more specific (and homogeneous)
      subgroups of patients.

PMID- 9543290
TI  - Accuracy of thermistors and thermocouples as flow-measuring devices for detecting
      hypopnoeas.
AB  - The aim of this work was to assess the accuracy of thermistors/thermocouples as
      devices for detecting hypopnoeas in sleep studies. Conventional
      thermistor/thermocouples were studied with a respiratory model allowing the
      simulation of inspiratory (22 degrees C) and expiratory (37 degrees C) flows. The
      thermistor signal (V'th) was compared with a pneumotachograph (V'th): 1) for
      sinusoidal and square-wave airflows (+/-0.05 to +/-0.8 L.s(-1), 10-20
      breaths.min(-1) (bpm)); 2) when changing the distance from the thermistor to the
      nose (0-20 mm); and 3) when doubling the section of the nostrils. The thermistor
      was strongly nonlinear and flow reductions (hypopnoeas) were underestimated: a
      50% reduction in V' (+/-0.5 L.s(-1), 15 bpm, sinusoidal) resulted in only an 18%
      reduction in V'th. V'th depended considerably on the airflow pattern: for V'=+/
      0.5 L.s(-1), V'th increased by 100% from sinusoidal (20 bpm) to square-wave (10
      bpm). For V'=+/-0.5 L.s(-1), 15 bpm, sinusoidal flow, V'th increased by 79% when
      the distance thermistor-nose varied from 20-0 mm, and V'th decreased by 37% when
      doubling the nose section. We concluded that thermistor/thermocouples are
      inaccurate flow-measuring devices when used at the airflow conditions typical of
      sleep studies. Their use for quantifying hypopnoeas may lead to considerable
      underdetection of these respiratory events.

PMID- 9543291
TI  - Assessment of the lactate biosensor methodology.
AB  - The rapid determination of lactate level is useful for clinical emergencies, as
      in the case of shock conditions or during surgical operations, as well as in
      numerous cases of respiratory failure, in cardiac or paediatric pathology and
      during exercise tests. Moreover, it is of prognostic significance in critically
      ill patients. Photometric methods are slow and, even when performed in good
      conditions, will give results only 30 min after blood collection, during which
      time the clinical condition of the patient may change. In this study, we have
      assessed the lactate biosensor, a method that yields lactate measurements in less
      than 1 min with only 100 microL of biological fluid. In order to test the
      validity of this method, we performed comparisons between the Sigma classical
      enzymatic reference method and two commercially available biosensors: the Ciba
      Corning biosensor 865 and the Yellow Springs lactate biosensor. Lactate
      measurements were performed in heparinized arterial blood samples without
      antiglycolitic agent (n=71). In order to cover a wide range of lactate levels,
      samples came from patients admitted to the intensive care unit for severe
      conditions and patients addressed for bicycle exercise testing. Each whole blood
      sample was processed in duplicate by both biosensors. For plasma measurement,
      subsamples of whole blood were centrifuged and the resulting plasma were
      processed by the biosensors and the Sigma method. Two parameters that can
      potentially influence lactate measurement were also investigated: haematocrit and
      total protein levels. The data showed that measurements performed on plasma are
      satisfactory for both biosensors. For whole blood, the Ciba-Corning device gives
      accurate results but the Yellow Springs apparatus seriously underestimates
      lactate levels. This underestimation is strongly influenced by the haematocrit
      level, so that a correction factor can be calculated (based on the haemoglobin
      level), which allows accurate "corrected" results to be obtained for whole blood
      with the Yellow Springs analyser.

PMID- 9543292
TI  - Eleven peak flow meters: a clinical evaluation.
AB  - Peak flow meters are essential tools in the management of asthma. Many types are
      on the market. A computer-driven piston pump is normally not available for
      evaluation of the various meters. Comparison with values from a pneumotachograph
      is an accepted way of testing peak flow meters. This study aims at comparing 11
      peak flow meters, for accuracy and linearity. Seven adult peak flow meters were
      tested: Miniwright with an equidistant scale (Clement Clarke); Personal Best
      (Healthscan); Wright Pocket fdE (Ferraris); Vitalograph (Vitalograph); Assess
      (Healthscan); Pocket Peak flow meter (Micro Medical); and Truzone (Monaghan).
      Furthermore, four low-range (LR) peak flow meters were tested: LR Miniwright with
      equidistant scale (Clement Clarke); LR Personal Best (Healthscan); LR Wright
      Pocket (LR Ferraris); and LR Pocket peak flow meter (LR Micro Medical). Two test
      series were performed: in the first one, a peak flow meter was connected
      downstream in series with a Fleisch #4 pneumotachograph. One subject performed 50
      partial forced expiratory manoeuvres through this ensemble. In the second series,
      50 adult patients and 25 healthy children performed sequential maximal forced
      expiratory manoeuvres on each peak flow meter, and on the pneumotachograph. A
      ranking system was devised for the various parameters of agreement of the meters
      with the pneumotachograph. Substantial differences in the quality of the adult
      meters were found. The adult peak flow meters with the closest agreement to the
      pneumotachograph were Personal Best and Micro Medical. In the low-range peak flow
      meters, the lowest differences were seen in the LR Personal Best and LR Micro
      Medical.

PMID- 9543293
TI  - Magnetic resonance imaging of the thorax in the evaluation of asbestosis.
AB  - The purpose of the study was to evaluate the accuracy of magnetic resonance
      imaging (MRI) in detecting subclinical morphological changes caused by asbestos
      exposure. Conventional chest radiographs according to the International Labour
      Organisation (ILO) categories 0-11 and spirometric data were compared with MRI in
      17 men with mean (+/-2SD) asbestos exposure time of 24.6+/-13.0 yrs. Mean age was
      62.0+/-9.4 yrs. The inclusion criterion was an ILO score of 2 or more.
      Electrocardiographic registrations and antirespiratory movement artefact
      techniques were used in all MRI examinations to avoid movement artefacts. Mean
      ILO grading was found to be 7.7+/-3.8 on chest radiography and 9.8+/-2.0 with MRI
      (p=0.01). Five patients had a higher ILO stage as evaluated by MRI, but in nine
      patients the staging remained unchanged. MRI revealed mediastinal adenopathy in
      four patients. Forced expiratory volume in one second (expressed as a percentage
      of the predicted value) was negatively correlated with ILO score as assessed by
      MRI (r=-0.4, p=0.032). Magnetic resonance imaging seems to be more sensitive than
      conventional radiographs in detecting subclinical fibrosis as well as the extent
      of pleural asbestosis.

PMID- 9543294
TI  - Functional evaluation of the lung resection candidate.
AB  - Advances in operative technique and perioperative care have considerably reduced
      surgical morbidity and mortality after pulmonary resections. Various single and
      combined parameters of functional operability have been proposed to assess the
      surgical risk. Pulmonary function tests adequately assess the pulmonary risk, and
      baseline or stress electrocardiography, echocardiography and nuclear cardiac
      studies assess the cardiac risk. Patients with normal or only slightly impaired
      pulmonary function (forced expiratory volume in one second (FEV1) and transfer
      factor of the lung for carbon monoxide (TL,CO) > or = 80% of predicted) and no
      cardiovascular risk factors can undergo pulmonary resections up to a
      pneumonectomy without further investigation. For others, exercise testing,
      pulmonary split-function studies, or a combination of these two methods are
      recommended. Exercise testing, most frequently performed as a symptom-limited
      test with the measurement of maximal oxygen uptake (V'O2,max), assesses both the
      pulmonary and cardiovascular reserves. A V'O2,max of <10 mL.kg(-1).min(-1) is
      generally considered prohibitive for any resection, a value of >20 mL.kg(-1).min(
      1) or >75% of predicted normal, safe for major resections. Split-function studies
      are radionuclide-based estimations of the predicted postoperative (ppo) values of
      various parameters. The currently used ppo-parameters are FEV1-ppo, TL,CO-ppo
      and, most recently, V'O2,max-ppo. Suggested cut-off values for safe resection
      are: for FEV1-ppo and TL,CO-ppo > or = 40% pred; and for V'O2,max > or = 35%
      pred, combined with an absolute value of > or = 10 mL.kg(-1).min(-1). The lowest
      acceptable ppo-values will still have to be established by additional prospective
      studies. In the long-term, resections involving not more than one lobe usually
      lead to an early functional deficit followed by later recovery. The permanent
      functional loss in pulmonary function is small (< or = 10%) and exercise capacity
      is only slightly reduced or not at all. Pneumonectomy, on the other hand, leads
      to an early permanent loss of about 33% in pulmonary function and 20% in exercise
      capacity. Thus, pulmonary function tests alone overestimate the functional loss
      after lung resection.

PMID- 9543295
TI  - Thoracoscopy--state of the art.
AB  - "Medical" thoracoscopy as compared with "surgical" thoracoscopy (which is more
      precisely known as video-assisted thoracic surgery (VATS)) has the advantage that
      it can be performed under local anaesthesia or conscious sedation, in an
      endoscopy suite, using nondisposible rigid instruments. Thus, it is considerably
      less invasive and less expensive. The main diagnostic and therapeutic indications
      for medical thoracoscopy are pleural effusions and pneumothorax. Due to its high
      diagnostic accuracy, approaching almost 100% in malignant and tuberculous pleural
      effusions, it should be used when pleural fluid analysis and needle biopsy are
      nondiagnostic. In addition, medical thoracoscopy provides staging for lung cancer
      and diffuse malignant mesothelioma. Talc poudrage, as the best conservative
      method for pleurodesis in 1998, can also be performed with medical thoracoscopy.
      It can also be effectively used in the early management of empyema. In
      spontaneous pneumothorax it allows staging, thereby facilitating treatment
      decisions, and in addition coagulation of eventual blebs and talc poudrage for
      efficient pleurodesis. Medical thoracoscopy is a safe procedure which is even
      easier to learn than flexible bronchoscopy. Due to its high diagnostic and
      therapeutic efficiency, it should be applied increasingly in the management of
      the above-mentioned pleuropulmonary diseases.

PMID- 9543296
TI  - Experimental models for studying mucociliary clearance.
AB  - Respiratory tract mucus is a viscoelastic gel, the rheological properties of
      which are determined mainly by its content of mucous glycoproteins and water. The
      rheology and quantity of mucus, in concert with ciliary factors, are the major
      determinants of mucociliary clearance. A wide range of animal models for studying
      the secretion and clearance of mucus are available. Ex vivo models, such as the
      frog palate or excised bovine trachea, provide direct, meaningful data regarding
      the clearability of mucus. Rodent models of chronic bronchitis, based on irritant
      gas or cigarette smoke exposure, show important features of the human condition
      in a relatively short time. The rheological characterization of mucus is made
      difficult by the small quantities obtainable, particularly from normal animals.
      Large animal models, such as the dog or sheep, although more expensive, offer
      many advantages, such as the ability to carry out long-term serial measurements,
      and to make integrated measurements of the clearance of mucus, ciliary function,
      epithelial ion transport, and the rheology of mucus in the same preparation.

PMID- 9543297
TI  - A childhood asthma death in a clinical trial: potential indicators of risk.
AB  - A 9 yr old girl with a history of eczema and asthma was admitted to our
      specialist asthma service and recruited into a trial designed to investigate
      systemic as well as therapeutic benefits of inhaled corticosteroids. Eight months
      after referral the patient died from an acute asthma attack. This childhood
      asthma death during an inhaled steroid trial has facilitated identification of
      risk factors. Despite good clinical response to inhaled corticosteroids, the
      patient was distinguishable from the other patients by: increased variability of
      the morning and evening peak flow rates; increased reactivity, though not
      sensitivity, to histamine; and an unprecedented rise in serum soluble interleukin
      2 receptor levels immediately after commencing inhaled steroids. The
      immunological basis for corticosteroid resistance and immunohistochemical studies
      on postmortem specimens from asthma deaths suggest that T-cell activation markers
      may be indicators of the fatality prone asthmatic.

PMID- 9543298
TI  - High-frequency ventilation augments the effect of inhaled nitric oxide in
      persistent pulmonary hypertension of the newborn.
AB  - Does inhaled nitric oxide (iNO) during high-frequency ventilation (HFV) lead to a
      more pronounced improvement in oxygenation than iNO during conventional
      ventilation? We report two cases of newborn infants with profound hypoxaemia, who
      did not respond with an increase in arterial oxygenation following iNO therapy
      during conventional mechanical ventilation. The first infant was a term neonate
      with persistent pulmonary hypertension of the newborn (PPHN) following postnatal
      hypoxia, the second patient a premature infant of 29 weeks of gestation with PPHN
      secondary to lung hypoplasia and perinatal asphyxia. After the initial failure of
      iNO we switched both neonates to HFV without NO, which did not lead to a
      significant improvement of oxygenation in either case. Shortly after the
      initiation of HFV a second trial of iNO was started. Both infants responded
      favourably to iNO with a marked and sustained increase in arterial oxygenation
      and absent right-to-left shunting via the ductus arteriosus and the foramen
      ovale. We conclude that the favourable response to inhaled nitric oxide is
      dependent on the degree of lung expansion and is more readily achieved by the use
      of high-frequency ventilation than conventional ventilation.

PMID- 9543299
TI  - Bronchoalveolar lavage cell analysis in a child with chronic lipid pneumonia.
AB  - In an asymptomatic 4 yr old child with radiographic evidence of parenchymal lung
      disease, bronchoalveolar lavage (BAL) yielded the diagnosis of chronic lipid
      pneumonia caused by chronic aspiration of mineral oil given as a laxative. BAL
      analysis showed a marked reduction in the total number of alveolar macrophages;
      almost 70% of these cells contained intracytoplasmic lipid vacuoles. It also
      disclosed lymphocytic (cytotoxic/suppressor) alveolitis. A high percentage of
      lymphocytes expressed antigen markers of activation (human leucocyte antigen
      (HLA)-DR), CD54 and CD25). BAL analysis 18 months after mineral oil intake
      revealed that lymphocytes bearing antigen markers of activation had markedly
      decreased whereas alveolar macrophages (normal and lipid-laden) had increased. A
      subsequent whole lung BAL was considered unnecessarily invasive in this otherwise
      healthy child.

PMID- 9543300
TI  - An unusual presentation of secondary pleural hydatidosis.
AB  - Although pleural involvement is relatively common in cystic hydatid disease, one
      of the rarest and least known complications is secondary pleural hydatidosis. We
      report the case of a patient who presented with polycystic secondary pleural
      hydatidosis 4 yrs after treatment for a pyopneumothorax caused by rupture of a
      pulmonary cyst near the pleural space. Due to the coexistence of severe chronic
      obstructive pulmonary disease, surgery was ruled out. The patient was treated
      with albendazole, with a favourable outcome.

PMID- 9543301
TI  - Multiple breath helium dilution measurement of lung volumes in adults.

PMID- 9543302
TI  - Corticosteroid-resistant asthma: pathogenesis and clinical implications for
      management.

PMID- 9543303
TI  - Prevalence of mood disorders in the rural population of Udmurtia.
AB  - A sample of 855 rural adult inhabitants of Udmurtia was interviewed by means of
      the Composite International Diagnostic Interview (CIDI) in order to investigate
      the incidence and prevalence of mood disorders. Depression affected 30.5% of the
      population according to ICD-10, and 22% according to DSM-III-R over a 12-month
      period. Depressive disorders were more common in women (40.5%) than in men
      (17.4%), and in subjects who were widowed (68.8%), divorced (55.6%) or had poor
      family relationships. Depression was not related to ethnicity, educational level,
      income or living conditions. Depression showed a high level of comorbidity with
      social phobia in Udmurts and with persistent somatoform pain disorder in Russian
      women. The annual incidence of depressive episode was 7.5%, and the highest risk
      of depression was among younger women and older men.

PMID- 9543304
TI  - Trauma exposure, postmigration stressors, and symptoms of anxiety, depression and
      post-traumatic stress in Tamil asylum-seekers: comparison with refugees and
      immigrants.
AB  - Compared to research on displaced persons whose refugee status has been endorsed
      prior to arriving in Western countries, there is little systematic information
      available about levels of past trauma, postmigration living difficulties and
      psychiatric symptoms amongst asylum-seekers who claim refugee status only after
      arrival. Asylum-seekers, authorized refugees and immigrants of Tamil background
      were recruited by personal contact and mail-out in Sydney, Australia. A total of
      62 subjects, constituting approximately 60% of the estimated pool of Tamil asylum
      seekers, agreed to participate in the study. They returned statistically
      significantly higher scores than immigrants (n = 104) on measures of past trauma,
      symptoms of anxiety, depression and post-traumatic stress, and on all dimensions
      of postmigration difficulties. Asylum-seekers did not differ from refugees (n =
      30) on measures of past trauma or psychiatric symptoms, but they scored higher on
      selective components of postmigration stress relating to difficulties associated
      with their insecure residency status. Although limited by sampling and diagnostic
      constraints, the present study suggests that asylum-seekers may be a high-risk
      group in relation to ongoing stress in the postmigration period.

PMID- 9543305
TI  - Executive deficits in major depression.
AB  - Clinically depressed patients and control subjects were examined by means of
      different tests to assess executive functions (the Wisconsin Card Sorting Test,
      the Stroop Color Word Test and a test of verbal fluency). The results indicate
      that the depressed patients were generally slower than the controls, as reflected
      by longer retrieval times for both words and colours. Furthermore, the depressed
      patients showed impairment with regard to altering behaviour appropriately in
      response to feedback. However, there were no depression-related increases in
      perseverative responses, and the ability to inhibit irrelevant information was
      unaffected by depression. No relationship was found between specific depressive
      symptoms or the severity of depression and cognitive performance. The overall
      pattern of results suggests that depression may affect various executive
      functions in a differentiated manner.

PMID- 9543306
TI  - Clinical characteristics of a total cohort of female and male applicants for sex
      reassignment: a descriptive study.
AB  - The objective of this study was to compare the features of female-to-male
      transsexuals (F-M) with those of male-to-female transsexuals (M-F) in the cohort
      of all applicants for sex reassignment over a 20-year period. In an
      observational, cross-sectional design the cohort was retrospectively identified,
      consisting of all 233 subjects who applied for sex reassignment in Sweden during
      the period 1972-1992. The cohort was subdivided into the groups M-F (n=134) and F
      M (n=99), and the two groups were compared. M-F were older when applying for sex
      reassignment surgery than F-M, and more often had a history of marriage and
      children than their F-M counterparts. M-F also had more heterosexual experience.
      F-M, on the other hand, more frequently exhibited cross-gender behaviour in
      childhood than did M-F transsexuals. The present and previous studies strongly
      support the view that transsexualism manifests itself differently in males and
      females. Various models for understanding these differences are discussed.

PMID- 9543307
TI  - The association between attitudes toward suicide and suicidal ideation in
      adolescents.
AB  - The aims of this study were to determine whether adolescent attitudes to suicide
      could be grouped into distinct factors, and then to examine the relationship
      between these factors and the psychosocial parameters known to be associated with
      suicide, and between attitudes towards suicide and suicidal ideation. A
      questionnaire designed to assess attitudes to suicide was distributed to a total
      of 525 Israeli adolescents. Statistical analysis indicated that the attitude
      items could be grouped into four distinct factors: the right of society to
      prevent suicide; suicide as a symptom of mental illness; the right of the
      individual to talk about suicide; and taking suicidal behaviour seriously. Each
      factor was differentially associated with the various psychosocial parameters
      examined. The association between the attitude factors and subjects' suicidal
      ideation was significant and at least as strong as that of the psychosocial
      parameters normally associated with adolescent suicide, namely gender and
      exposure to suicide. A generally approving attitude towards suicide was
      correlated with a high level of suicidal ideation.

PMID- 9543308
TI  - Fatigue mood as an indicator discriminating between anorexia nervosa and bulimia
      nervosa.
AB  - In order to clarify the differences in mood states between anorexia and bulimia
      nervosa, the Profile of Mood States (POMS) with tension-anxiety, depression,
      anger-hostility, vigour, fatigue and confusion scales was administered to 32
      female patients with anorexia nervosa (age range 14 to 32 years, mean age 20
      years), 49 female patients with bulimia nervosa (age range 15 to 33 years, mean
      age 23 years) and 410 'normal' female subjects (age range 14 to 35 years, mean
      age 23 years). The scores on the depression, fatigue and confusion scales for
      both anorexia and bulimia nervosa and those on the tension-anxiety and anger
      hostility scales for bulimia nervosa were significantly higher than those for the
      control subjects. The score on the fatigue scale for bulimia nervosa was
      significantly higher than that for anorexia nervosa. Moreover, the result of the
      multiple logistic regression analysis including all of the POMS scales indicated
      that the fatigue scale significantly discriminated between the two disorders.
      Fatigue mood appears to be a principal indicator for differentiating between the
      two disorders.

PMID- 9543309
TI  - Eating disorders and insulin-dependent diabetes mellitus (IDDM): relationships
      with glycaemic control and somatic complications.
AB  - This study was designed to assess (by means of a diagnostic interview based on
      DSM-III-R criteria) the prevalence of eating disorders in 69 insulin-dependent
      diabetic (IDDM) out-patients, and the relationship with somatic risks. We found
      no cases of anorexia nervosa or bulimia nervosa, current or lifetime, in male
      patients with IDDM. No female patients with IDDM had anorexia, and 4.8% had
      current and lifetime bulimia. Eating disorders not otherwise specified (bulimic
      type) were significantly more frequent in women than in men (lifetime incidence
      43% vs. 21%; current incidence 33% vs. 5%), and generally occurred after the
      onset of IDDM. Self-reports of bulimic behaviours according to the Bulimic
      Investigatory Test of Edinburgh (BITE) were associated with high levels of
      glycosylated haemoglobin. There was no association between eating disorders
      (current or lifetime), with somatic complications being more likely to be
      explained by a long duration of illness and impaired glycaemic control.

PMID- 9543311
TI  - Factors affecting the development of spontaneous recurrence of methamphetamine
      psychosis.
AB  - The process triggering spontaneous recurrences of methamphetamine (MAP) psychosis
      (i.e. flashbacks) was studied in 41 flashbackers, along with 84 non-flashbackers
      with a history of MAP psychosis. Plasma monoamine metabolite levels were assayed
      in 25 of the 41 flashbackers, 16 of the 84 non-flashbackers, 9 subjects with
      persistent MAP psychosis and 28 control subjects. All flashbackers had
      experienced threatening events or frightening paranoid-hallucinatory states
      during previous MAP use. The dominant factor triggering flashbacks was a mild
      fear of other people. Plasma norepinephrine levels were elevated during
      flashbacks. The results suggest that a mild fear of other people may have
      elicited memories of MAP psychosis associated with threatening experiences
      through increased sensitivity to psychosocial stressors. As a result the
      flashbacks occurred, including an increase in peripheral noradrenergic activity.

PMID- 9543310
TI  - Collaboration with drug treatment by schizophrenic patients with and without
      psychoeducational training: results of a 1-year follow-up.
AB  - Within a controlled prospective intervention study, schizophrenic outpatients
      randomly assigned to four treatment groups and one control group were assessed
      with regard to collaboration with drug treatment. In total, 39.3% of 84 regular
      attenders of the psychoeducational training programme and 26.6% of 64 control
      patients reported having persuaded their psychiatrists to modify their medication
      prescriptions. A total of 8.3% and 7.8%, respectively, modified their medication
      on their own initiative, although with subsequent approval by the psychiatrist,
      and 20.2% and 15.6%, respectively, modified their medication after consulting
      their psychiatrist. With regard to medication management, the groups did not
      differ either at post-treatment or at follow-up. At follow-up, regular attenders
      showed a reduced fear of side-effects, increased confidence in their medication
      and stable confidence in their physician. Among the control subjects, confidence
      in the medication and in their physician declined, and fear of side-effects
      increased. Psychoeducational training therefore led to an optimization of
      patients' attitudes toward treatment, but not to changes in medication
      management.

PMID- 9543312
TI  - A prevalence study of folate deficiency in a psychiatric in-patient population.
AB  - Controlled clinical trials in the UK have shown folate deficiency in psychiatric
      patients, and it has been suggested that such deficiency is most likely to occur
      among patients with affective disorders. Studies have led to the use of folate as
      an adjunct to therapy in such patients. The present paper describes a preliminary
      investigation into the red cell folate status of psychiatric patients in a
      general hospital unit compared with age- and sex-matched healthy controls, using
      up-to-date assays and strict entry criteria and overall improved methods on
      previous studies. The study showed that, although there is a trend for
      psychiatric patients to have lower serum folate levels than controls, there is no
      statistically significant difference in folate levels as measured by red cell
      folate, a more reliable measure of folate status, between healthy controls and
      psychiatric patients, and all but one of the patients had normal haematological
      indices.

PMID- 9543313
TI  - Amitriptyline vs. lorazepam in the treatment of opiate-withdrawal insomnia: a
      randomized double-blind study.
AB  - Benzodiazepine use in the treatment of insomnia may cause benzodiazepine
      dependence, especially in opiate users. The aim of this study was to investigate
      the sedative-hypnotic effects of amitriptyline in treating opiate-withdrawal
      insomnia. A total of 27 patients with opiate withdrawal were given either
      amitriptyline or lorazepam in a randomized double-blind trial. Sleep was assessed
      by means of the Sleep Evaluation Questionnaire and three insomnia items of the
      Hamilton Depression Rating Scale. The scores of two sleep measures showed that
      all aspects of sleep, except for ease of awakening from sleep, in the two
      treatment groups were not significantly different. In conclusion, apart from the
      hangover effect, amitriptyline is as effective as lorazepam in the treatment of
      opiate-withdrawal insomnia.

PMID- 9543314
TI  - Naturalistic experience with the use of divalproex sodium on an in-patient unit
      for adolescent psychiatric patients.
AB  - This paper focuses on the importance of data collected not only from controlled
      clinical trials, but also from naturalistic treatment experience. In particular
      we examine the use of divalproex sodium either as monotherapy or as part of
      combined therapy on an in-patient ward for adolescents aged 13-18 years. All
      admissions in which divalproex sodium use was attempted (n=36) were analysed over
      a 1-year period. The most common use was in patients with a mixed-presentation
      bipolar disorder (n=16), followed by patients with major depression (n=7), mania
      (n=4) or psychoses not otherwise specified (n=4). Divalproex sodium use was
      evaluated in the control of mania, psychosis, agitation, mood swings, aggression
      and/or anxiety. Overall, the use of divalproex sodium was associated with a
      marked improvement along all psychopathological variables in the vast majority of
      patients. Few side-effects or medical complications were noted. We believe that
      divalproex sodium is a potentially useful drug in adolescent patients with
      varying forms of psychopathology.

PMID- 9543315
TI  - Severe motor-dominant neuropathy with IgM M-protein binding to the NeuAcalpha2
      3Galbeta- moiety.
AB  - We report the occurrence of a relapsing, severe predominantly motor neuropathy in
      a 75-year-old man with an IGM-K M-protein binding to gangliosides GM2, GM3, GM4,
      GD1a, GT1b and LM1. Motor nerve conduction velocities were slowed with conduction
      block. A superficial peroneal nerve biopsy specimen revealed segmental
      demyelination and remyelination. The patient improved after repeated plasma
      exchanges, and the antibody titer decreased in association with clinical
      recovery. This IgM M-protein has a unique, previously unreported binding
      specificity for terminal NeuAcalpha2-3Galbeta- moiety in common to all
      gangliosides bound by the antibody except GM2. M-proteins with this affinity may
      be involved in the pathogenesis of this and other cases of motor-dominant
      demyelinating neuropathy.

PMID- 9543316
TI  - Bulbocavernosus reflex studies and autonomic testing in the diagnosis of erectile
      dysfunction.
AB  - The electrophysiologic evaluation of patients with erectile dysfunction presents
      an important diagnostic challenge. The bulbocavernosus reflex (BCR) latency has
      been commonly used to evaluate these disorders. However, it is a measure of
      somatic penile innervation, whereas erection is primarily dependent on autonomic
      function. We evaluated 195 men with erectile dysfunction over a 3 year period.
      Each had electrophysiologic studies, nerve conduction studies and a BCR. BCR
      studies were abnormal in only 7%, of which most had diabetes or pelvic trauma.
      The BCR was the sole electrophysiologic abnormality in only 2%. Autonomic testing
      (AT) was additionally performed in 19 diabetic and 23 non-diabetic patients. This
      included sympathetic skin responses and measurement of the Valsalva ratio and
      heart rate variability with 6/min breathing. In the diabetic group, AT was
      positive in 63%, and most often was the sole abnormality. The bulbocavernosus
      reflex is relatively insensitive in the diagnosis of erectile dysfunction. Brief
      autonomic testing may provide valuable additional data, particularly in
      diabetics.

PMID- 9543317
TI  - Acute cytomegalovirus infection and IgM anti-GM2 antibody.
AB  - Guillain-Barre syndrome (GBS) sometimes is preceded by cytomegalovirus (CMV)
      infection. Irie et al. (J. Neuroimmunol. 1996;68:19-26) reported that three
      patients with GBS subsequent to CMV infection had IgM and IgG anti-GM2
      antibodies. In our larger study, the IgMs from the CMV-associated GBS patients
      showed significantly higher anti-GM2 antibody titers than anti-GM3, anti-GD1a,
      anti-GD1b, anti-GD2, anti-GD3, anti-GT1b, anti-GQ1b, and anti-SGPG antibody
      titers. None of the anti-glycosphingolipid antibody titers differed significantly
      from the others in the IgGs from the CMV-associated GBS patients. However, IgM
      anti-GM2 antibody frequently was present in GBS patients who were not preceded by
      CMV infection and non-GBS patients with acute CMV infection. Our results did not
      support the conclusion of Irie et al. that anti-GM2 antibodies were closely
      associated with acute CMV infection in GBS, but acute CMV infection, with and
      without GBS, was associated with IgM anti-GM2 antibody.

PMID- 9543318
TI  - Alteration of spatial-temporal parameters of gait in Chronic Fatigue Syndrome
      patients.
AB  - Chronic Fatigue Syndrome (CFS) has been widely studied and a lot of information
      is available in the literature regarding the immunological, virological,
      neuroendocrinal and psychiatric aspects of the disease, but its aetiology is
      still poorly understood. Great attention has also been paid to the alteration of
      the muscular function caused by CFS. The aim of the present work was to study CFS
      patients' gait in order to find out objective measures which can better
      characterize the pathology. Spatial and temporal parameters of gait were
      collected from a group of 12 CFS informed volunteers by using the typical
      instrumentation of movement analysis, and raw data were statistically elaborated.
      Comparisons with reference data from a population of healthy subjects revealed
      significant abnormalities in the symmetry indices of the bilateral parameters and
      in the linear relationships among parameters, and between these parameters and
      the physical characteristics of the patients. Interestingly, the abnormalities
      were present as from the beginning of the gait, which indicates that they are
      unlikely to be caused by the rapid increasing fatigue. This strengthens the
      hypothesis of a direct involvement of the central nervous system (CNS) in the
      onset of the disease.

PMID- 9543319
TI  - Microvascular endothelial activation in the skeletal muscles of patients with
      multiple organ failure.
AB  - The relationship between microvascular damage and the presence of muscle fibre
      atrophy and necrosis has been investigated in skeletal muscle biopsies taken from
      57 patients with multiple organ failure. Immunohistochemical studies showed no
      loss of capillaries and no luminal thrombosis, while neutrophil leucocytes were
      more prevalent in the patients' biopsies than in controls. Deposition of the
      complement membrane attack complex (C5-9MAC) in capillaries was observed in 41%
      of cases. Endothelial activation was suggested by an increased intensity of
      expression of ICAM-1, and by an increased proportion of capillaries expressing P
      selectin and E selectin, although this was not directly associated with
      neutrophil accumulation. Endothelial swelling was present in many biopsies with
      38% of the biopsies having larger capillary profiles on immunohistochemical
      labelling for von Willebrand factor (vWF), thrombomodulin and CD34, and on Ulex
      europaeus agglutinin 1 binding. Endothelial swelling was confirmed by image
      analysis and morphometric evaluation of capillary ultrastructure, however, the
      capillary luminal area was not reduced as the capillaries were dilated. Increased
      vWF labelling was associated with C5-9MAC deposition and with fibre necrosis, but
      the vascular changes were not related to fibre atrophy nor to clinical indices of
      the severity of the patients' illness. The results suggest that microvascular
      damage and ischaemia may not be major factors in the pathogenesis of muscle fibre
      damage in multiple organ failure, but that endothelial activation is a common
      occurrence. The variability in the patterns of markers of endothelial activation,
      and the small proportion of capillaries affected, may reflect the complexity of
      the endothelial response to circulating or locally produced cytokines.

PMID- 9543320
TI  - Adverse changes in fibre type composition of the human masseter versus biceps
      brachii muscle during aging.
AB  - The fibre composition of functionally different regions, the superficial and the
      deep portions, of the human masseter and the biceps brachii muscles of six
      elderly subjects (mean age 74 years) was studied by morphological and enzyme
      histochemical methods. When compared to previous data for young adults, the
      masseter muscle from elderly subjects showed a significant decrease in the
      proportion of type I fibres and an increase of type IM and II fibre types,
      concomitant with muscle fibre atrophy. In the old biceps, there were no changes
      in the type I fibre proportion and fibre diameter, but a significant decrease in
      the type IIB fibre content. The present results of changes in fibre composition,
      in addition to previous findings of functional deterioration of the old masseter,
      probably reflect a combination of age related degenerative and adaptive processes
      within the trigeminal neuromuscular system. When compared with previous findings
      in young adult masseter, it can be concluded that the human masseter muscle
      differs from limb muscles both in fibre composition and in structural response of
      the muscle during aging. These differences between the masseter and the biceps
      brachii muscle suggest muscle specific alterations during aging probably due to
      differences in genetical control, functional performance and nerve and hormonal
      influences.

PMID- 9543321
TI  - Clinical diagnosis in Karwinskia humboldtiana polyneuropathy.
AB  - Intoxication by Karwinskia humboldtiana presents a neurological picture similar
      to that for Guillain-Barre syndrome or other polyradiculoneuropathies. Clinical
      diagnosis in poisoned humans may be difficult if no evidence of previous fruit
      ingestion is available. We present our experience in the clinical diagnosis of
      Karwinskia humboldtiana polyneuropathy, as confirmed by toxin detection in blood.
      We designed an open trial at the Pediatric Neurology service and included all
      cases with acute ascending paralysis that were admitted to our hospital in the
      last two years. In all cases, we performed hematological, immunological and
      biochemical profiles, CSF analysis including immunological studies, oligoclonal
      bands and myelin basic protein determinations. Electrodiagnostic studies were
      performed, including motor conduction velocities, distal latencies, F-wave
      latency and compound muscle action potential (CAMP) amplitude. The presence of
      Karwinskia humboldtiana toxins in blood were determined by thin layer
      chromatography. In six cases, T-514 Karwinskia humboldtiana toxin was detected.
      These cases had a symmetric motor polyneuropathy with the absence of tendon
      reflexes and no sensory signs or cranial nerve involvement. Only one patient
      required assisted ventilation due to bulbar paralysis. In two of these cases, a
      sural nerve biopsy revealed a segmental demyelination with swelling and
      phagocytic chambers in Schwann cells and without lymphocytic infiltration. All
      six cases survived, with complete recovery in five. We conclude that this
      intoxication is common in Mexico. The availability of toxin detection in blood
      samples allows the clinician to establish an accurate diagnosis and should be
      included in the study of children with polyradiculoneuropathy, especially in
      countries where this poisonous plant grows.

PMID- 9543322
TI  - Positron emission tomography in vascular dementia.
AB  - BACKGROUND: Vascular dementia (VaD) is an ill-defined entity. It is not known how
      acute brain failure related to stroke becomes chronic leading to dementia.
      PURPOSE: The present study investigates whether positron emission tomography
      (PET) can detect different metabolic patterns in VaD. PATIENTS AND METHODS: Four
      groups of stroke patients were selected. The PET findings of 14 stroke patients
      with multiple large infarcts and dementia (MID) and 14 without dementia (MS) were
      compared. Sixteen stroke patients with lacunes, leukoaraiosis and dementia (LD)
      were assessed against nine without dementia (LS). The PET examination utilised
      the 15-O-steady-state technique in order to determine regional cerebral blood
      flow (rCBF), regional oxygen extraction rate (rOER) and regional cerebral
      metabolic rate for oxygen (rCMRO2) in different pre-established cortical,
      subcortical and cerebellar regions. RESULTS: Decreased coupled mean rCBF and
      rCMRO2 with comparable rOER values were observed in all cerebral regions except
      in the cerebellum of the MID compared to the MS group. In the LD group mean rCBF
      and rCMRO2 were decreased with increased rOER in all cerebral regions except in
      the cerebellum compared to the LS group. CONCLUSIONS: The PET findings in
      demented patients with multiple large infarcts are in agreement with the concept
      of multi-infarct dementia. In demented patients with lacunes and leukoaraiosis,
      the PET pattern suggests a state of misery perfusion not only in the deep
      structures but also in the whole cerebral cortex. The present PET study argues
      that there are at least two possible mechanisms that can explain the occurrence
      of VaD in stroke patients.

PMID- 9543323
TI  - Gly341Arg mutation indicating malignant hyperthermia susceptibility: specific
      cause of chronically elevated serum creatine kinase activity.
AB  - We report on three families with the Gly341Arg ryanodine receptor gene (RYR1)
      mutation. Thirteen individuals were heterozygote carriers of the Gly341Arg
      mutation and had clearly positive in vitro contracture tests, indicating
      malignant hyperthermia susceptibility. Nine Gly341Arg mutation positive
      individuals from two families had elevated serum creatine kinase (CK) activity at
      rest (up to six times the normal upper limit). Their clinical and neurological
      examinations as well as detailed muscle histology were normal. The third family
      did not show increased CK activity. These findings indicate that the Gly341Arg
      mutation can be a specific cause of chronically elevated serum CK activity in
      asymptomatic individuals.

PMID- 9543324
TI  - Clinicopathological features of chronic inflammatory demyelinating
      polyradiculoneuropathy in childhood.
AB  - The clinical, electrophysiological, and pathological findings, and the
      therapeutic characteristics in ten children with chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP), whose onset age was less than 16
      years, were evaluated. The clinical progression pattern of the initial phase
      divided the patients into two groups. One group (six patients) showed a subacute
      progression for up to 2 months after onset and a subsided progression over 3
      months. Three patients in this group had a preceding febrile episode. The other
      group (four patients) showed a chronic insidious progression for more than 3
      months. The former group of patients revealed a favourable response to
      corticosteroid therapy as compared with the latter group. However, other clinical
      and laboratory features at the peak impairment were not distinguishable between
      these two groups. Motor dominant neuropathy was common to all patients, and only
      three cases showed sensory disturbance on the distal limbs. No cases revealed
      cranial nerve involvement. Motor and sensory nerve conduction and sural nerve
      biopsy studies revealed the demyelinating nature of the neuropathy. These
      clinicopathological features suggest that the subacute progression form
      frequently associated with prodromal episode and rather favourable corticosteroid
      response is characteristic in childhood CIDP, while the chronic insidious
      progression form is indistinguishable from the common adult CIDP.

PMID- 9543325
TI  - Roussy-Levy syndrome is a phenotypic variant of Charcot-Marie-Tooth syndrome IA
      associated with a duplication on chromosome 17p11.2.
AB  - The Roussy-Levy syndrome (MIM #180800) was described in 1926 as a disorder
      presenting with pes cavus and tendon areflexia, distal limb weakness, tremor in
      the upper limbs, gait ataxia and distal sensory loss. We report a family with
      affected members in four generations, showing these clinical signs of Roussy-Levy
      syndrome and a partial duplication at chromosome 17p11.2. This genetic defect is
      commonly found in patients with the hypertrophic form of the Charcot-Marie-Tooth
      syndrome. Our finding provides evidence against the Roussy-Levy syndrome as a
      distinct entity but suggests a close relation with the Charcot-Marie-Tooth
      syndrome. What causes the additional features of gait ataxia and essential tremor
      needs further clarification.

PMID- 9543326
TI  - Propentofylline enhances cerebral metabolic response to auditory memory
      stimulation in Alzheimer's disease.
AB  - To evaluate efficacy, safety, metabolic and clinical effects of propentofylline
      in Alzheimer's disease (AD), a prospective, randomized, double-blind, placebo
      controlled trial was performed in 30 patients with mild to moderate AD who
      underwent pretreatment and posttreatment 18F-2-fluoro-2-deoxy-D-glucose positron
      emission tomography under resting conditions and during stimulation with an
      auditory memory paradigm. Twenty-eight subjects completed the 3-month study. The
      drug was well tolerated. In the active treatment group, a significant increase of
      cerebral metabolic response to the memory task was observed (multiple measurement
      ANOVA P = 0.02). The placebo group showed a significantly decline in the MMSE
      score (P = 0.02) while there was no change in the treatment group. This suggests
      a protective role for propentofylline in slowing the progression of AD.

PMID- 9543327
TI  - Substantial spontaneous long-term remission in subacute sclerosing
      panencephalitis (SSPE).
AB  - We report a 25-year-old female who developed clinical and electroencephalographic
      (EEG) features of subacute sclerosing panencephalitis (SSPE) at the age of 17
      years. After almost 17 months of progressive neurological deterioration to a
      level where she was bedridden and incapable of self-care (Risk and Haddad stage
      3a), she experienced a substantial spontaneous clinical and EEG remission (stage
      4c) which she has maintained for the last 8 years. The measles antibody titer in
      the cerebrospinal fluid (CSF), however, progressively increased during follow-up.
      There are only very few patients with well documented diagnosis of SSPE who have
      maintained such a prolonged remission. The age at onset of SSPE of > or = 12
      years, disappearance of periodic complexes and a tendency for normalization of
      the background activity in the EEG, and a progressive increase in the measles
      antibody titer in the CSF appears to predict a favourable outcome of SSPE.

PMID- 9543328
TI  - Case report: a veterinarian who collapsed after the delivery of a calf by
      cesarean section.
AB  - We report a patient who experienced internal carotid artery dissection with
      cerebral ischemia and cranial nerve involvement. The clinical features, the
      diagnostic approach and the therapeutic options are discussed in view of the
      recent literature.

PMID- 9543329
TI  - Horner's syndrome associated with mononeuritis multiplex due to cytomegalovirus
      as the initial manifestation in a patient with AIDS.
AB  - We report on a 60-year-old male with AIDS who presented Horner's syndrome that
      was associated with mononeuritis multiplex due to cytomegalovirus (CMV)
      infection. This is the first case who presented Homer's syndrome in the course of
      AIDS. Horner's syndrome associated with mononeuritis multiplex in this patient
      was the initial manifestation without any opportunistic infections. Since
      Horner's syndrome and mononeuritis multiplex in the present case were both
      improved by ganciclovir, it is important to consider CMV infection when Horner's
      syndrome or mononeuritis multiplex is observed in immunocompromised patients,
      such as those with HIV-1 infection or AIDS, even if they do not show any other
      opportunistic infections.

PMID- 9543330
TI  - Uncommon presentations of neurocysticercosis.
AB  - Neurocysticercosis commonly presents with seizures, raised intracranial tension
      and dementia. The unusual location of the cysts may result in uncommon
      manifestations mimicking a host of neurological disorders. Ten patients with
      neurocysticercosis with rare clinical presentations have been described in this
      series. These include dorsal midbrain syndrome, isolated bilateral ptosis,
      papillitis, cerebral hemorrhage, painful cervical radiculopathy, progressive
      swelling of arm, paraplegia due to intramedullary cyst, third ventricular cyst,
      dystonia and nominal aphasia masquerading as transient ischaemic attacks. The
      clinical details and possible mechanisms for these rare presentations are
      discussed.

PMID- 9543331
TI  - Recurrent cranial neuropathy as a clinical presentation of idiopathic
      inflammation of the dura mater: a possible relationship to Tolosa-Hunt syndrome
      and cranial pachymeningitis.
AB  - We report 14 patients with idiopathic recurrent cranial neuropathy, in whom
      multiple cranial nerves were involved recurrently, either at the same or
      different times, and appeared bilaterally. Oculomotor nerve involvement was most
      frequent, while the abducens and facial nerves were the next most frequent.
      Clinical courses were benign and not progressive, and the symptoms responded well
      to corticosteroids. Ten patients developed Tolosa-Hunt syndrome during the course
      of their illness. Laboratory findings and CSF were normal. MRI and CT studies
      were unremarkable, except for an asymmetric appearance of the cavernous sinus in
      some patients. One patient showed focal hypertrophic pachymeningitis in the
      posterior fossa in MRI. We discuss the relationship of the idiopathic recurrent
      cranial neuropathy with disorders characterized by inflammation of the dura
      mater, such as Tolosa-Hunt syndrome and cranial pachymeningitis.

PMID- 9543332
TI  - Non-familial olivopontocerebellar atrophy combined with late onset Alzheimer's
      disease: a clinico-pathological case report.
AB  - A 76-year-old woman with olivopontocerebellar atrophy (OPCA) presented with
      progressive intellectual deterioration. She showed cerebellar ataxia and muscle
      atrophy and weakness, and gradually developed generalized dementia with
      visuospatial disturbance. An autopsy revealed numerous senile plaques (SPs),
      neurofibrillary tangles (NFTs) and neuropil threads particularly in the CA1,
      subiculum and entorhinal cortex and to a lesser degree in the cerebral neocortex
      shown by immunostaining and specific silver impregnation techniques. The nucleus
      basalis of Meynert had numerous NFTs with fibrillary gliosis and neuronal cell
      loss. The basis pontis was markedly atrophied and the pontine nucleus had severe
      neuronal depopulation and gliosis. The pontine transverse fibers were
      demyelinated with their axons being fragmented. The cerebellar white matter was
      also severely degenerated. The striatum, Onuf's and intermediolateral nuclei of
      the spinal cord remained unchanged. Ubiquitin immunohistochemistry and Gallyas
      silver impregnation technique revealed oligodendroglial inclusions in the pontine
      nucleus, corticopontine tract, cerebral and cerebellar white matter. On double
      immunostaining of KP1 and ubiquitin, globular neurite SPs encircled by KP1
      positive fibrous structures were found in the hippocampus and cerebral neocortex.
      The curly neurite SPs contained KP1-positive granules. The KP1-positive
      microglial cells were distributed widely in the cerebral white matter and HLA-DR
      positive ones were found around the SPs. The present case showed generalized
      dementia compatible with Alzheimer's disease (AD) and had a pathologically limbic
      type of late onset AD. This is the first case where AD affected non-familial
      OPCA.

PMID- 9543333
TI  - Localized muscle wasting as an initial symptom of skeletal muscle lymphoma.
AB  - A 25-year-old man who developed painless muscle wasting and weakness of only the
      right thigh, was eventually shown to have systemic lymphoma with muscle
      infiltration. The patient was initially misdiagnosed as focal inflammatory
      myopathy, and he had a partial response to steroid therapy. Immunohistochemical
      analysis of the biopsied muscle and the subcutaneous tumor revealed the
      infiltrating cells with a positive macrophage-associated marker (CD68) and
      negative T- or B-cell-associated antigens, leading to the final diagnosis of true
      histiocytic lymphoma. Although skeletal muscle lymphoma is extremely rare, it
      should be considered in the differential diagnosis of localized muscle wasting.

PMID- 9543334
TI  - Suprachiasmatic nucleus in a patient with multiple system atrophy with abnormal
      circadian rhythm of arginine-vasopressin secretion into plasma.
AB  - We performed a quantitative investigation of arginine-vasopressin (AVP)
      immunopositive neurons in the suprachiasmatic nucleus (SCN), which is the
      endogenous clock of the brain of a patient with multiple system atrophy (MSA) who
      exhibited nocturnal polyuria associated with decreased urinary specific gravity
      and depression of nocturnal AVP secretion. Eleven age- and sex-matched subjects
      were used as controls. Although, the number of AVP-positive neurons was decreased
      in neither the supraoptic nucleus nor the paraventricular nucleus, the number of
      AVP-positive neurons in the SCN was decreased and gliosis was present in the SCN.
      The cytoplasmic area of AVP-immunopositive neurons in the SCN was smaller in the
      patient than in the control subjects. These findings raise the possibility that
      SCN is involved in MSA and the neurodegeneration in the SCN results in altered
      circadian rhythm of AVP secretion and nocturnal polyuria.

PMID- 9543335
TI  - Neurulation in the rabbit embryo.
AB  - Among a broad range of factors and mechanisms involved in the complex process of
      neurulation a relationship between the curvature of the craniocaudal body axis
      and rate of neural tube closure has been proposed, but more examples and models
      are needed to further substantiate the existence of this relationship. This is
      particularly true for mammals, where marked differences in embryonic body
      curvature between species exist. The rabbit embryo has virtually no curvature
      during the main phase of neurulation and is therefore a suitable model, but
      neurulation is hardly documented in this species. In the present study,
      therefore, neural tube closure in the rabbit embryo is presented in detail by
      morphological and morphometrical parameters, as well as from scanning electron
      microscopic investigations. At the stages of 6-8 somites, the flat neural plate
      transforms into a V-shaped neural groove, beginning at the rhombo-cervical level.
      Between the stages of 8 and 9 somites, multiple closure sites occur
      simultaneously at three levels: at the incipient pros-mesencephalic transition,
      at the incipient mes-rhombencephalic transition, and at the level of the first
      pairs of somites. This results in four transient neuropores. The anterior and
      rhombencephalic neuropores close between the stages of 9-11 somites. The
      mesencephalic neuropore is very briefly present. The posterior neuropore is the
      largest and remains longest. Its tapered (cranial) portion closes fast within
      somite stages 9-10. Subsequently its wide (caudal) portion closes up to a narrow
      slit, but further closure slows down till full closure is achieved at the 22
      somite stage. In comparing rabbit neurulation with that of chick and mouse, the
      sequence of multiple site closure resembles that of the mouse embryo, but other
      important aspects of neurulation resemble those of the chick embryo. In contrast
      to mouse and chick, no time lag between closure at the three closure sites in the
      rabbit was seen.

PMID- 9543336
TI  - Expression of the axon growth-related neural adhesion molecule TAG-1/axonin-1 in
      the adult mouse brain.
AB  - TAG-1/axonin-1 is a neuronal cell adhesion molecule of the immunoglobulin
      superfamily. It is predominantly expressed during neural development and has been
      reported to be involved in axonal growth and pathfinding. Here, the expression of
      TAG-1/axonin-1 was investigated anatomically in the adult mouse brain by in situ
      hybridization using digoxigenin-labeled cRNA probes. Low levels of TAG-1/axonin-1
      could be detected in cerebellar granule cells, in tufted and mitral cells of the
      olfactory bulb, and in pyramidal cells of area CA1 and CA3 of the hippocampus. We
      suspect that the expression of TAG-1/axonin-1 in these structures of the adult
      brain may serve neural plasticity.

PMID- 9543337
TI  - Normal ontogenic observations on the expression of Eph receptor tyrosine kinase,
      Cek8, in chick embryos.
AB  - The spatio-temporal pattern of expression for the Eph receptor tyrosine kinase,
      Cek8, was observed in normal chick embryos from H-H stage 6 to 23 by
      immunohistochemical techniques. Expression of Cek8 was already present in embryos
      at H-H stage 6, where it was located in the neural plate of the brain region,
      paraxial mesoderm, and the primitive streak. Regions expressing Cek8 subsequently
      increased during development to include the neural folds of the brain,
      rhombomeres 3 and 5, the caudal part of the neural plate, neural crest cells
      related to the formation of glossopharyngeal nerve ganglia, invaginated cells
      throughout the primitive groove and the epithelium of the rudiment of the gall
      bladder. Cek8 was also expressed in the mesenchymal cells of the pharyngeal
      arches, allantoic stalk and limb buds as well as in the areas surrounding the eye
      vesicles and nasal pits. Furthermore, cells in the tail bud progressing to the
      secondary neurulation expressed Cek8. Thus, the spatiotemporal patterns of Cek8
      expression appears to have intimate relationships with tissue rebuilding, the
      maturation of differentiated cells, and the spatial organization of tissues.
      Consequently, it appears that Cek8 plays an integral role in the developmental
      events leading to the formation of a wide--though not inclusive--variety of
      tissues and organ systems.

PMID- 9543338
TI  - Immunohistochemistry and in situ hybridization of the androgen receptor in the
      developing human prostate.
AB  - As it is suggested that the androgen receptor mechanism is required for prostatic
      development, we attempted to determine the appearance, expression and
      distribution of the androgen receptor in embryonic, infantile and pubertal human
      prostate. Using mono- and polyclonal antibodies and a digoxigenin-labeled 713 bp
      riboprobe, the androgen receptor expression in paraffin sections of fetal,
      infantile, and pubertal prostates was studied at the protein and RNA level. Under
      highly standardized conditions, application of the polyclonal antibodies resulted
      in a weak cytoplasmic and nuclear labeling of the epithelium of fetal glands. No
      immunoreaction was obtained with monoclonal antibodies. Applying the polyclonal
      antibody to pubertal and adult specimens, immunoreactivity of the androgen
      receptor was positive in nuclei of adluminal and basal epithelial cells, in
      interstitial and vascular smooth muscle cells and vascular endothelium, whereas
      ganglionic cells and enteroendocrine cells were negative. In situ hybridization
      with the digoxigenin-labeled riboprobe gave clear positive results already in
      epithelium of very young fetal specimens. A semiquantitative visual evaluation of
      in situ hybridizations showed that intermediate intensity of expression was
      increased in pubertal and adult specimens, whereas strong expression was reduced
      in prostatic epithelium. CONCLUSIONS: The essential findings are: (1) an early
      expression of androgen receptor mRNA in the fetal prostate; (2) no immunoreaction
      of monoclonal antibodies against the androgen receptor in the same specimens, (3)
      a decrease of androgen receptor mRNA expression, but increase in immunoreactivity
      of the androgen receptor protein with the onset of glandular maturation during
      puberty.

PMID- 9543340
TI  - Development of the male urogenital system of the koala phascolarctos cinereus.
AB  - This paper described several developmental stages of the male urogenital system
      in the koala Phascolarctos cinereus, employing both light and scanning electron
      microscopy. There are few studies of the development of the urogenital system in
      male marsupials. Findings by White and Timms (1994) that male koalas can be
      infected with Chlamydia psittaci emphasise the importance of studies on male
      animals and in particular their reproductive system. Specimens in our study
      ranged in age from 15 days postnatal to adults. Due to the rarity of such
      specimens, details of each specimen are linked to the changes of the structures
      at each available stage. Light microscopy revealed that differentiation of the
      gonads had commenced by 15 days postnatal and that the cytological arrangements
      of the urogenital system are essentially the same as those of other mammals.
      Scanning electron microscopy revealed stereocilia and microvilli along the lumen
      of each ductus epididymis and cilia and microvilli along the lumina of the vasa
      deferentia and urethra. The development of these structures coincided with the
      onset of sexual maturation, sperm production and differentiation at about three
      years of age.

PMID- 9543339
TI  - Differential expression of lactoseries carbohydrate epitopes HNK-1, CD15, and
      NALA by olfactory receptor neurons in the developing chick.
AB  - The formation of the nasal lining with its sensory and its nonsensitive
      respiratory epithelium requires a spatially ordered pattern of cellular
      differentiation. Aiming at identifying cell recognition molecules that may be
      involved in cellular differentiation steps, we applied a panel of antibodies to
      terminal carbohydrate sequences of the lactoseries on the developing chick
      olfactory epithelium. This approach is based on the idea that these terminal
      sugar residues may be involved in certain steps of maturation. Restricted
      expression of three epitopes NALA, HNK-1, and CD15 was observed in olfactory
      receptor neurons. The first immature olfactory receptor neurons were observed by
      day 3 of incubation, expressing the HNK-1 epitope, whereas a total epithelial
      staining was observed for NALA. By day 9 of incubation high numbers of HNK-1
      positive immature olfactory receptor neurons were observed. At the same time
      mature olfactory receptor neurons showed immunoreactivity for CD15, whereas NALA
      was still expressed throughout the whole epithelial cell population. However,
      there was a pronounced staining in the population of mature olfactory receptor
      neurons. Around hatching only CD15 was detectable in (mature) olfactory receptor
      neurons, whereas HNK-1 and NALA immunoreactivity have switched to glandular and
      sustentacular cells respectively. The differentiation-dependent expression
      patterns of these three cell surface molecules suggest them as suitable markers
      to explore mechanisms that determine embryonic olfactory receptor neurogenesis.

PMID- 9543341
TI  - Ontogeny of NADPH-diaphorase in rat forebrain and midbrain.
AB  - This study characterizes the developmental expression of NADPH-diaphorase from
      embryo to adulthood in the forebrain, midbrain and cerebellum of rat brain via
      histochemical staining. On embryonic day 12 no neurons stained. Labeling was
      observed in certain nuclei from E15 through the postnatal period to adulthood.
      Labeling in neurons increased or maintained a constant level with increased age.
      The embryo demonstrated substantial labeling in neurons of the caudate putamen,
      bed nucleus of the stria terminalis, preoptic area, lateral hypothalamic area,
      paraventricular thalamic nucleus, ventromedial hypothalamic nucleus,
      magnocellular nucleus posterior commissure, and periaqueductal central gray.
      Additional neuronal labeling was observed postnatally in the olfactory bulb,
      cerebral cortex, amygdala, various nuclei of the thalamus, interpeduncular
      nucleus, linear nucleus of the raphe, pretectal area and superior colliculus. In
      the cerebellum, labeling appeared only after P14 in cells of the molecular cell
      layer and granular cell layer. The sizes of labeled neurons developed
      significantly from P4 to P14 in several nuclei. The distinctive temporal and
      spatial expression pattern of NADPH-diaphorase implies that the NO/cGMP system
      may play an important role in physiological and developmental functions.

PMID- 9543342
TI  - Induction of monocyte chemotactic protein-1 (MCP-1) and TNF alpha by Trichinella
      spiralis in serum of mice in vivo.
AB  - MCP-1 is a small (8-10 KDa) protein and a prototype member of the CC chemokine
      beta subfamily, which plays a critical role in acute and chronic inflammation.
      Recent evidence suggests an important role for MCP- 1, MCP-2 and MCP-3 in a
      number of pathological states, including delayed type hypersensitivity
      conditions, parasitic infections and rheumatoid arthritis. Forty BALB-c mice were
      treated with the parasite Trichinella spiralis. After the infection the animals
      were sacrificed at different periods from the initial infection and MCP-1 and
      TNFalpha were quantified in the mouse serum. The level of MCP-1 in the serum of
      mice infected with 100 larvae increases from 27.5+/-7.0 pg/ml at day 23, to a
      maximum level of 31.5+/-5.0 pg/ml at day 33, then decreased to 14.6+/-2.0 pg/ml
      at day 47. When the mice were infected with 200 larvae of T. spiralis the maximum
      increase was 34.4+/-2.5 pg/ml found on day 23. From day 33 to day 47 MCP-1 levels
      were decreased. In addition, in infected mice levels of TNFalpha were detectable
      in the serum as early as day 1. The level of TNFalpha was maximum at day 35
      (3812+/-224 pg/ml). Serum from non-infected mice contained no detectable levels
      of either MCP-1 or TNFalpha. However, even if MCP-1 seems to be implicated in
      Trichinellosis, its exact role and function in inflammatory parasitic diseases
      remains to be determined.

PMID- 9543343
TI  - Possible role of GH/IGF-1 in the ovarian function of adult hypothyroid rats.
AB  - We have monitored estrous cycle and measured serum estradiol, GH, IGF-1, T4 and
      T3 levels in adult hypothyroid female rats which were divided into four groups: H
      group, hypothyroid rats without treatment; H-T4 group, hypothyroid rats injected
      daily with T4; HT4-PTU group, hypothyroid rats injected daily with T4 plus PTU
      (propylthiouracil), and H-T4-IOP group, hypothyroid rats injected daily with T4
      plus IOP (iopanoic acid); Euthyroid rats (E group) were used as control. Our
      results indicate that the lack of sexual cycle in H animals was associated with
      lower values of estradiol, GH and IGF-1 in comparison to E group; the restoration
      of sexual cycle in H-T4 group was associated with values of estradiol, GH and IGF
      1 higher than those of H group, whereas in H-T4-PTU and H-T-IOP groups the
      restoration was associated with higher values of GH and IGF-1 and values of
      estradiol similar to those of H group. These data could suggest a potential role
      of GH/IGF-1 axis, at least in part, in the lack of sexual cycle in H group and in
      the ovulation induction in H-T4, H-T4-PTU and H-T4-IOP groups.

PMID- 9543344
TI  - Purification of guinea pig small intestinal peroxisomes and the subcellular
      localization of glucose-6-phosphate dehydrogenase.
AB  - A method for the isolation of highly purified peroxisomes from guinea pig small
      intestine was developed. This two-stage process involved a rate-dependent banding
      of a light-mitochondria lambda-fraction followed by a density-dependent banding
      of the catalase enriched fractions obtained from the first step, using a
      horizontal rotor. Furthermore, the subcellular localization of glucose-6
      phosphate dehydrogenase (NADP+-dependent) activity in guinea pig small intestine
      was examined. Analysis of density-gradient fractions indicated that approximately
      3-4% of the cellular NADP+-dependent glucose-6-phosphate dehydrogenase activity
      is associated with peroxisomal fractions and that it is localized to the matrix
      of peroxisomes. It is therefore suggested that a peroxisomal source of NADPH may
      be utilized by enzyme systems that use NADPH specifically as a reductant.

PMID- 9543345
TI  - Human mitochondrial function during cardiac growth and development.
AB  - Little information is presently available concerning mitochondrial respiratory
      and oxidative phosphorylation function in the normal human heart during growth
      and development. We investigated the levels of specific mitochondrial enzyme
      activities and content during cardiac growth and development from the early
      neonatal period (10-20 days) to adulthood (67 years). Biochemical analysis of
      enzyme specific activities and content and mitochondrial DNA (mtDNA) copy number
      was performed with left ventricular tissues derived from 30 control individuals.
      The levels of cytochrome c oxidase (COX) and complex V specific activity, mtDNA
      copy number and COX subunit II content remained unchanged in contrast to
      increased citrate synthase (CS) activity and content. The developmental increase
      in CS activity paralleled increasing CS polypeptide content, but was neither
      related to overall increases in mitochondrial number nor coordinately regulated
      with mitochondrial respiratory enzyme activities. Our findings of unchanged
      levels of cardiac mitochondrial respiratory enzyme activity during the
      progression from early childhood to older adult contrasts with the age-specific
      regulation found with CS, a Krebs cycle mitochondrial enzyme.

PMID- 9543346
TI  - Sodium selenate corrects glucose tolerance and heart function in STZ diabetic
      rats.
AB  - Sodium selenate, administered intraperitoneally (i.p.), resulted in an
      improvement in glucose tolerance in treated diabetic rats. Fed rat plasma glucose
      levels were reduced by selenate treatment in streptozotocin diabetic rats. The
      lowest values of blood glucose were reached within 3 weeks of beginning the
      treatment. Food and fluid consumption was reduced in treated compared to
      untreated diabetic rats. Diabetic treated rats did not release insulin in
      response to a glucose challenge and insulin release in response to a challenge
      was markedly reduced in control treated rats. Assessment of heart function using
      a working heart apparatus showed that treated diabetic rats with improved blood
      glucose levels had normal heart function at 8 weeks of diabetes in contrast to
      hearts from non-treated diabetics. This study extends previous observations on
      the in vivo insulin-like effects of sodium selenate.

PMID- 9543347
TI  - Hepatic heterogeneity in the response to ATP studied in the bivascularly perfused
      rat liver.
AB  - The zonation of the purinergic action of ATP in the hepatic parenchyma was
      investigated in the bivascularly perfused rat liver by means of anterograde and
      retrograde perfusion. Livers from fed rats were used, and ATP was infused
      according to four different experimental protocols: (A) anterograde perfusion and
      ATP infusion via the portal vein; (B) anterograde perfusion and ATP via the
      hepatic artery; (C) retrograde perfusion and ATP via the hepatic vein; (D)
      retrograde perfusion and ATP via the hepatic artery. The following metabolic
      parameters were measured: glucose release, lactate production and oxygen
      consumption. The hemodynamic effects were evaluated by measuring the sinusoidal
      mean transit times by means of the indicator-dilution technique. ATP was infused
      during 20 min at four different rates (between 0.06-0.77 micromol min[-1] g
      liver[-1]; 20-200 microM) in each of the four experimental protocols. The results
      that were obtained allow several conclusions with respect to the localization of
      the effects of ATP along the hepatic acini: (1) In retrograde perfusion the
      sinusoidal mean transit times were approximately twice those observed in
      anterograde perfusion. ATP increased the sinusoidal mean transit times only in
      retrograde perfusion (protocols C and D). The effect was more pronounced with
      protocol D. These results allow the conclusion that the responsive
      vasoconstrictive elements are localized in a pre-sinusoidal region; (2) All
      hepatic cells, periportal as well as perivenous, were able to metabolize ATP, so
      that concentration gradients were generated with all experimental protocols.
      Extraction of ATP was more pronounced in retrograde perfusion, an observation
      that can be attributed, partly at least, to the longer sinusoidal transit times.
      In anterograde perfusion, the extraction of ATP was time-dependent, a phenomenon
      that cannot be satisfactorily explained with the available data; (3) ATP produced
      a transient initial inhibition of oxygen uptake when protocols A and B were
      employed. These protocols are the only ones in which the cells situated shortly
      after the intrasinusoidal confluence of the portal vein and the hepatic artery
      were effectively supplied with ATP. The decrease in oxygen consumption was more
      pronounced at low ATP infusions when protocol B was employed. These observations
      allow the conclusion that the former phenomenon is localized mainly in cells
      situated shortly after the intrasinusoidal confluence of the portal vein and
      hepatic artery. Oxygen consumption in all other cells, especially the proximal
      periportal ones, is increased by ATP; (4) In agreement with previous data found
      in the literature, glycogenolysis stimulation by ATP was more pronounced in the
      periportal region. The cells that respond more intensively are not the proximal
      periportal ones, but those situated in the region of the intrasinusoidal
      confluence of the portal vein and the hepatic artery.

PMID- 9543348
TI  - Immunodetection of ralA and ralB GTP-binding proteins in various rat tissues and
      platelets.
AB  - Polyclonal antibodies were generated against a synthetic peptide corresponding to
      the C-terminal (amino acids 192-204) region of ralA and ralB GTP-binding
      proteins. The ralA and ralB antibodies recognized a 27 kDa protein in the human
      platelet particulate fraction. Incubation of ralA antibodies with ralB immunizing
      peptide and ralB antibodies with ralA immunizing peptide prior to Western
      blotting did not abolish the ability of antibodies to recognize the 27 kDa
      protein in human platelet particulate fraction. However, when antibodies were
      incubated with the respective immunizing peptide prior to Western blotting, the
      27 kDa human platelet protein was no longer recognized by the antibodies.
      Incubation of nitrocellulose blots containing polypeptides separated using SDS
      PAGE with [alpha-32P]GTP demonstrated the presence of GTP-binding proteins of
      molecular mass between 23-27 kDa in rat platelets and the various tissues tested.
      Analysis using subtype specific antibodies demonstrated that both ralA and ralB
      GTP-binding proteins were expressed in rat platelets and the various tissues
      tested. The protein recognized by the ralA and ralB antibodies in rat tissues and
      platelets had mobility on SDS-PAGE identical to that of the human platelet ral
      protein. Varying amounts of these proteins were detected in all the tissues
      tested except white muscle which contained very low level of ralB protein. The
      widespread distribution of ralA and ralB GTP-binding proteins suggests that they
      may participate in a common pathway in mammalian cells and tissues.

PMID- 9543349
TI  - Respiratory muscle injury: is it important?

PMID- 9543350
TI  - Respiratory muscle injury in animal models and humans.
AB  - Respiratory muscle injury may result from excessive loading due to a decrease in
      respiratory muscle strength, an increase in the work of breathing, or an increase
      in the rate of ventilation. Other conditions such as hypoxemia, hypercapnia,
      aging, decreased nutrition, and immobilization may potentiate respiratory muscle
      injury. Respiratory muscle injury has been shown in animal models using direct
      muscle or phrenic nerve stimulation, acute inspiratory resistive loading,
      tracheal banding, corticosteroids, phrenic nerve section, and the mdx mouse.
      Although numerous examples of diaphragm injury have been shown in animal models,
      evidence in humans is sparse. Potential mechanisms which may contribute to
      respiratory muscle injury include high levels of intracellular calcium-activated
      degradative enzymes, non-uniformity of stresses and strains, plasma membrane
      disruptions, and activation of the inflammatory process.

PMID- 9543351
TI  - Determinants of diaphragmatic injury.
AB  - Limb muscles can be injured during and after vigourous contractions. However,
      this injury is most evident under specific conditions. The strength and type of
      muscle contraction as well as the contractile status of the muscle are important
      determinants of injury. The initiating event leading to muscle injury is not
      clearly understood but there are several leading theories. The respiratory
      muscles are of obvious importance to survival, and fatigue or injury to them has
      been hypothesized to be prevented by various mechanisms. One such mechanism is
      reduced activation by the central nervous system. In this review information on
      the neural activation of the breathing muscles during inspiratory loading is
      discussed and reveals that neural activation to the diaphragm, the main
      inspiratory muscle, is high. Previous studies investigating the presence of
      muscle fatigue immediately after such inspiratory loading have shown little
      evidence of it. However, based on information from limb muscles, delayed or
      secondary muscle injury might occur and could produce deleterious effects on
      respiratory muscle function. Recent evidence shows that chronic low intensity
      inspiratory loading can produce diaphragmatic injury (Reid et al.) and secondary
      or delayed muscle injury can occur three days after an acute period of high
      intensity inspiratory loading. The results reviewed in this article suggest that
      the respiratory muscles, specifically the diaphragm, are not spared from injury
      or the results of muscle injury. Diaphragmatic function during the period of
      secondary muscle injury is markedly impaired and thus respiratory muscle injury
      is a phenomenon that warrants further investigation.

PMID- 9543352
TI  - Respiratory muscle dysfunction in mechanically-ventilated patients.
AB  - The interaction between a patient and a ventilator is the major determinant of
      the amount of respiratory muscle rest achieved by the machine. We are beginning
      to acquire a better understanding of the mechanisms that underlie this complex
      interaction, but this information has yet to be integrated into the routine
      clinical management of ventilator-supported patients. To achieve that goal, we
      need better techniques of detecting and monitoring patient-ventilation
      asynchrony, and the development of simple algorithms that can minimize its
      occurrence. Finally, research is needed to determine the occurrence and
      importance of respiratory muscle fatigue during failed weaning attempts so as to
      better guide the timing and pace of the weaning process in problematic patients.

PMID- 9543353
TI  - Free radical induced respiratory muscle dysfunction.
AB  - It is now recognized that respiratory muscle fatigue contributes to the
      development of respiratory failure in some patients with lung disease. This
      observation has prompted an examination into the mechanisms of development of
      muscle fatigue, with the understanding that an elucidation of these processes may
      lead to new therapeutic approaches to the treatment of these patients. A series
      of recent studies examining this issue have, moreover, discovered that oxygen
      derived free radicals generated during strenuous contraction may modulate
      respiratory muscle contractile function and contribute to the development of
      muscle fatigue. The data supporting this concept include: (a) direct (e.g. EPR,
      ESR studies) and indirect (evidence of lipid peroxidation, protein carbonyl
      formation, glutathione oxidation) evidence that there is heightened free radical
      production in contracting muscle, (b) evidence that pharmacologic depletion of
      muscle antioxidant stores increases degree of muscle fatigue present after a
      period of exercise, and (c) evidence that administration of agents that act as
      free radical scavengers retard the development muscle fatigue. Free radicals may
      produce these changes in muscle force generating capacity by interacting with and
      altering the function of a number of intracellular-biophysical processes (i.e.
      sarcolemmal action potential propagation, sarcoplasmic reticulum calcium
      handling, mitochondrial function, contractile protein interactions).

PMID- 9543354
TI  - The molecular basis of activity-induced muscle injury in Duchenne muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is the most common of the human muscular
      dystrophies, affecting approximately 1 in 3500 boys. Most DMD patients die in
      their late teens or early twenties due to involvement of the diaphragm and other
      respiratory muscles by the disease. The primary abnormality in DMD is an absence
      of dystrophin, a 427 kd protein normally found at the cytoplasmic face of the
      muscle cell surface membrane. Based upon the predicted structure and location of
      the protein, it has been proposed that dystrophin plays an important role in
      providing mechanical reinforcement to the sarcolemmal membrane of muscle fibers.
      Therefore, dystrophin could help to protect muscle fibers from potentially
      damaging tissue stresses developed during muscle contraction. In the present
      paper, the nature of mechanical stresses placed upon myofibers during various
      forms of muscle contraction are reviewed, along with current lines of evidence
      supporting a critical role for dystrophin as a subsarcolemmal membrane
      stabilizing protein in this setting. In addition, the implications of these
      findings for exercise programs and other potential forms of therapy in DMD are
      discussed.

PMID- 9543355
TI  - Respiratory muscle dysfunction in sepsis.
AB  - It became evident in the past 12 years that venitlatory muscle contractile
      performance is significantly impaired during the course of septic shock. In
      animal models of septic shock, depression of ventilatory muscle contractile
      performance has been shown to cause hypercapneic ventilatory failure and
      respiratory arrest. Failure of ventilatory muscle contractility in septic shock
      has never been attributed to a single factor, but two groups of factors are
      likely to be involved: (a) increased ventilatory muscle metabolic demands due to
      augmentation of ventilation, hypoxemia and increased pulmonary impedance; and (b)
      specific cellular, metabolic, immune and hemodynamic defects which interfere with
      several processes necessary for normal force generation. These defects are
      mediated by complex interactions between several local and systematic mediator
      such a bacterial endotoxin, proinflammatory cytokines, prostaglandins, platelet
      activating factor, reactive oxygen species and nitric oxide. This is a summary of
      how these interactions are likely to interfere with ventilatory muscle
      contractile performance in septic shock with particular emphasis on the newly
      described role of nitric oxide.

PMID- 9543356
TI  - Exercise-induced muscle injury: a calpain hypothesis.
AB  - It is well established that periods of increased contractile activity result in
      significant changes in muscle structure and function. Such morphological changes
      as sarcomeric Z-line disruption and sarcoplasmic reticulum vacuolization are
      characteristic of exercise-induced muscle injury. While the precise mechanism(s)
      underlying the perturbations to muscle following exercise remains to be
      elucidated, it is clear that disturbances in Ca2+ homeostasis and changes in the
      rate of protein degradation occur. The resulting elevation in intracellular
      [Ca2+] activates the non-lysosomal cysteine protease, calpain. Because calpain
      cleaves a variety of protein substrates including cytoskeletal and myofibrillar
      proteins, calpain-mediated degradation is thought to contribute to the changes in
      muscle structure and function that occur immediately following exercise. In
      addition, calpain activation may trigger the adaptation response to muscle
      injury. The purpose of this paper is to: (i) review the chemistry of the calpain
      calpastatin system; (ii) provide evidence for the involvement of the non
      lysosomal, calcium-activated neutral protease (calpain) in the response of
      skeletal muscle protein breakdown to exercise (calpain hypothesis); and (iii)
      describe the possible involvement of calpain in the inflammatory and regeneration
      response to exercise.

PMID- 9543357
TI  - Simultaneous stiffness and force measurements reveal subtle injury to rabbit
      soleus muscles.
AB  - The time course of force generation and the time course of muscle stiffness were
      measured in rabbit soleus muscles during eccentric contraction to understand the
      underlying basis for the force loss in these muscles. Muscles were activated for
      600 msec every 10 sec for 30 min. Soleus muscles contracting isometrically
      maintained constant tension throughout the treatment period, while muscles
      subjected to eccentric contraction rapidly dropped tension generation by 75%
      within the first few minutes and then an additional 10% by the end of 30 min.
      This indicated a dramatic loss in force-generating ability throughout the 30 min
      treatment period. To estimate the relative number of cross-bridges attached
      during the isometric force generation phase immediately preceding each eccentric
      contraction, stiffness was measured during a small stretch of a magnitude equal
      to 1.5% of the fiber length. Initially, muscle stiffness exceeded 1300 g/mm and,
      as eccentric treatment progressed, stiffness decreased to about 900 g/mm. Thus,
      while muscle stiffness decreased by only 30% over the 30 min treatment period,
      isometric force decreased by 85%. In isometrically activated muscles, stiffness
      remained constant throughout the treatment period. These data indicate that,
      while soleus muscles decreased their force generating capability significantly,
      there were a number of cross-bridges still attached that were not generating
      force. In summary, the loss of force generating capacity in the rabbit soleus
      muscle appears to be related to a fundamental change in myosin cross-bridge
      properties without the more dramatic morphological changes observed in other
      eccentric contraction models. These results are compared and contrasted with the
      observations made on muscles composed primarily of fast fibers.

PMID- 9543358
TI  - Cytokines in exertion-induced skeletal muscle injury.
AB  - Cytokines are a diverse family of intercellular signaling proteins that influence
      the movement, proliferation, differentiation, metabolism and membrane processes
      of target cells. Synthesis and release of cytokines from leukocytes in response
      to microbial stimuli are well known. This review, however, will present evidence
      that non-infectious stimuli can induce cytokine secretion from leukocytes and
      other cells (including muscle cells) following myocellular injury. The biological
      actions and potential adaptive values of these cytokines through the course of
      muscle necrosis and regeneration will be described.

PMID- 9543361
TI  - Pediatric renal transplantation without steroids.
AB  - Pediatric renal transplant patients present a number of challenges and problems,
      especially the inhibited post-transplant growth seen in children receiving
      standard immunosuppressive triple therapy that includes steroids. We report the
      successful use of steroid-free immunosuppression since 1990 in 14 pediatric renal
      allograft recipients who received a 10-day initial course of anti-lymphocyte
      globulin and surface area-adjusted doses of cyclosporine, 7 of whom also received
      mycophenolate mofetil (MMF) as maintenance immunosuppression. Only 1 patient died
      (3 months after transplantation as a result of a primary Epstein-Barr virus
      infection-induced lymphoproliferative disorder), 1 patient's graft never
      functioned, and another patient lost his graft after 3 years because of chronic
      rejection. Three patients experienced early acute cellular rejection, which
      resolved in 2 cases with OKT3, and in the 3rd with MMF. There were no late acute
      rejections. All patients evidenced growth and a growth spurt under this regimen.
      We conclude that all the pediatric patients benefited from our steroid-free
      protocol and that this protocol is superior to conventional triple therapies,
      which entail the eventual reduction and discontinuation of steroids, a procedure
      that not only inhibits growth but also carries an additional risk of acute
      rejection due to a steroid-adapted immune response.

PMID- 9543360
TI  - Cellular responses in exertion-induced skeletal muscle injury.
AB  - Muscle injury is a common result of muscle exertion caused by overload and over
      activity. In this presentation, an attempt was made to discuss models of muscle
      injury which involve exertion but not excessive strain, although most functional
      activities of the extremities require some eccentric muscle actions. Muscle
      injury is characterized by cellular and extracellular matrix responses which
      appear to be common to all types of muscle trauma -- even in the absence of
      bleeding. Using tenotomy and functional over-load of the rat hindlimb muscles as
      examples, illustrations of several of these responses are presented and
      discussed.

PMID- 9543363
TI  - Pediatric renal biopsy: should this procedure be performed in an outpatient
      setting?
AB  - Although several retrospective reports suggest that pediatric outpatient renal
      biopsies may be done in a safe and cost-effective manner, risk factors and the
      natural history of major complications following this procedure have not been
      clearly delineated. In an effort to determine the minimal observation period
      required to detect major post-renal biopsy complications in children and to
      establish clinical parameters predictive of these complications, a retrospective
      review of 177 percutaneous renal biopsies was performed. The overall major
      complication rate was 3.4%, while the minor complication rate was 14.1%. The mean
      percentage change in hemoglobin 4-10 h postbiopsy in patients with major bleeding
      complications was significantly greater than patients with minor bleeding
      complications. Using a 16% drop in hemoglobin 4-10 h postbiopsy, the sensitivity
      and specificity of identifying a major bleeding complication was 100% and 98%,
      respectively, while the positive and negative predictive value was 68% and 100%,
      respectively. All patients with major complications due to excess sedation or
      immediate bleeding were diagnosed within 11 h of the biopsy. Automated renal
      biopsies offered several safety and efficiency advantages compared with non
      automated methods. Our results suggest that outpatient pediatric renal biopsies
      should be encouraged provided certain precautions are taken to reduce the risk of
      developing major complications.

PMID- 9543362
TI  - Hepatitis G virus infection in children on dialysis and after renal
      transplantation.
AB  - The aim of the present study was to use a combination of the reverse
      transcription-polymerase chain reaction and a new diagnostic test for antibodies
      against the viral envelope protein E2 to assess the prevalence of hepatitis G
      virus (GBV-C/HGV) infection in sera of Hungarian children on hemodialysis (HD) or
      peritoneal dialysis (CAPD), as well as in sera of renal transplant patients
      (RTx). The GBV-C/HGV RNA prevalence was significantly higher in the whole group
      of children with renal failure (18.5%) than in the control group (children with
      urinary tract infection, 2.5%). The difference between the GBV-C/HGV RNA
      prevalence in the RTx group (33.3%) and in the control group (2.5%) was
      significant (P = 0.007). Anti-E2, which is considered an indicator of a past GBV
      C/ HGV infection, was detected in 10% (1/10) of HD patients, in 33.3% (4/12) of
      RTx patients, but in none of the children on CAPD. These differences were not
      significant. Children receiving a renal graft are at an increased risk of
      developing GBV-C/HGV infection, which may be attributed to the immunosuppressive
      drugs necessary to maintain the grafts.

PMID- 9543364
TI  - Steroids in the hemolytic uremic syndrome.
AB  - To determine whether steroids could be of clinical benefit in the treatment of
      the hemolytic uremic syndrome (HUS), we conducted a randomized, double-blinded,
      placebo-controlled trial of methylprednisone (5 mg/kg per day in four oral doses
      over 7 days), in children with HUS during the acute phase. Ninety-two patients
      with typical HUS (47 receiving placebo and 45 receiving steroids) were
      investigated for neurological, hematological, and nephrological variables. There
      were no differences between groups in the number of convulsive episodes or
      transfusion requirements during the hospital stay. Serum creatinine levels were
      slightly increased on day 10 in the placebo group compared with the steroid group
      (P = 0.06) and declined significantly between days 1 and 10 only in the steroid
      group (P = 0.001). In the 51 patients with anuria (24 placebo, 27 steroids),
      median serum creatinine levels were reduced in the steroid group compared with
      the placebo group on the 10th day (P = 0.01). Differences in median days of
      oliguria [11.5 versus 8 (P = 0.28)], anuria [5 versus 7 (P = 0.20)], and dialysis
      [12 versus 10 (P = 0.26)] for the placebo and the steroid group respectively were
      not significant. Our data suggest that oral steroids are not able to modify
      hematological, neurological, or nephrological clinical parameters during the
      acute phase of childhood HUS, even though they do seem to be associated with a
      more rapid decline in serum creatinine levels.

PMID- 9543365
TI  - The paucity of minimal change disease in adolescents with primary nephrotic
      syndrome.
AB  - Data are sparse regarding the histological lesions associated with the primary
      nephrotic syndrome in adolescents. To our knowledge there are only two published
      articles that have specifically addressed the histopathological lesions that
      typify idiopathic nephrotic syndrome in the adolescent population. We reviewed
      our experience from the last 14 years of children between the ages of 12 and 18
      years who were referred to our center for the evaluation of the nephrotic
      syndrome. A total of 29 adolescents met the inclusion criteria for this review.
      All patients were biopsied prior to the initiation of treatment. The sex ratio
      consisted of 52% males and 48% females and the racial breakdown was largely
      African-American, with 83% black adolescents, 7% Hispanic, and 10% Caucasian
      patients. Minimal change nephrotic syndrome (MCNS), the predominant lesion of
      children at an early age, was noted in only 20% of patients. The majority of
      patients (55.2%) had focal segmental glomerulosclerosis (FSGS); 7% had IgM
      nephropathy and 3.5% had diffuse mesangial hypercellularity. Only 7% of biopsied
      adolescents had membranoproliferative glomerulonephritis. Our results indicate
      that the most common lesion in this predominantly African-American patient
      population is FSGS, with only a small number showing MCNS. Thus, in our
      experience derived from a racially mixed population, adolescents with the
      nephrotic syndrome are less likely to have MCNS than younger children.

PMID- 9543359
TI  - Inflammatory responses to ischemia and reperfusion in skeletal muscle.
AB  - Skeletal muscle ischemia and reperfusion is now recognized as one form of acute
      inflammation in which activated leukocytes play a key role. Although restoration
      of flow is essential in alleviating ischemic injury, reperfusion initiates a
      complex series of reactions which lead to neutrophil accumulation, microvascular
      barrier disruption, and edema formation. A large body of evidence exists which
      suggests that leukocyte adhesion to and emigration across postcapillary venules
      plays a crucial role in the genesis of reperfusion injury in skeletal muscle.
      Reactive oxygen species generated by xanthine oxidase and other enzymes promote
      the formation of proinflammatory stimuli, modify the expression of adhesion
      molecules on the surface of leukocytes and endothelial cells, and reduce the
      bioavailability of the potent antiadhesive agent nitric oxide. As a consequence
      of these events, leukocytes begin to form loose adhesive interactions with
      postcapillary venular endothelium (leukocyte rolling). If the proinflammatory
      stimulus is sufficient, leukocytes may become firmly adherent (stationary
      adhesion) to the venular endothelium. Those leukocytes which become firmly
      adherent may then diapedese into the perivascular space. The emigrated leukocytes
      induce parenchymal cell injury via a directed release of oxidants and hydrolytic
      enzymes. In addition, the emigrating leukocytes also exacerbate ischemic injury
      by disrupting the microvascular barrier during their egress across the
      vasculature. As a consequence of this increase in microvascular permeability,
      transcapillary fluid filtration is enhanced and edema results. The resultant
      increase in interstitial tissue pressure physically compresses the capillaries,
      thereby preventing microvascular perfusion and thus promoting the development of
      the no-reflow phenomenon. The purpose of this review is to summarize the
      available information regarding these mechanisms of skeletal muscle
      ischemia/reperfusion injury.

PMID- 9543366
TI  - Glomerular growth in childhood focal segmental glomerulosclerosis.
AB  - Studies have suggested that glomerular size increases in childhood minimal lesion
      with age or growth. To examine whether mean glomerular volume (MGV) of pediatric
      patients with focal segmental glomerulosclerosis (FSGS) also increases with age
      and whether FSGS by itself can contribute to glomerular hypertrophy, we studied
      67 children (40 boys, 27 girls) with primary FSGS and 95 children (68 boys, 27
      girls) with minimal lesion by morphometry. FSGS patients had segmental sclerosis
      affecting 17.1% +/- 14.8% of the glomeruli. The percentage of segmental
      glomerulosclerosis was not related to age. MGV increased with age in the FSGS
      patients (r2 = 0.36, P < 0.001) and in the minimal lesion patients (r2 = 0.37, P
      < 0.001). MGV of children with FSGS is significantly larger than that of the
      minimal lesion group [(14.8 +/- 5.7) x 10(5) microm3 vs. (12.1 +/- 3.7) x 10(5)
      microm3, P < 0.001]. Multiple regression estimates suggest that the FSGS lesion
      affects MGV independently (P < 0.001). The volume density of mesangium and the
      volume density of cortical interstitium were significantly greater in the FSGS
      patients than in the minimal lesion patients (P < 0.001). These results indicate
      that MGV of pediatric FSGS patients increases with age and that the FSGS lesion
      itself may cause glomerular hypertrophy, possibly via mesangial expansion. Thus,
      glomerular hypertrophy in childhood minimal lesion may be an indicator of FSGS
      that is undetected because of the problem of sampling.

PMID- 9543367
TI  - Systemic juvenile rheumatoid arthritis complicated by two different renal
      lesions.
AB  - Systemic-onset juvenile rheumatoid arthritis (JRA) is a complex disease which
      affects many organ systems. Associated renal lesions are unusual, with the
      possible exception of amyloidosis. We describe a girl with systemic-onset JRA who
      developed first membranous nephropathy and then, 3.5 years later, a severe
      crescentic glomerulonephritis. The membranous lesion followed therapy with
      intravenous immune globulin, and the possibility that this intervention caused
      the renal disease must be considered. It appears that both of these lesions
      should be added to the list of possible complications of systemic-onset JRA.

PMID- 9543368
TI  - In situ hybridization of hepatitis B DNA in hepatitis B-associated
      glomerulonephritis.
AB  - Renal tissues from 43 of 49 children with hepatitis B virus-associated
      glomerulonephritis (HBV-GN) were examined for HBV DNA by in situ hybridization
      (ISH) assay within the last 10 years. HBV DNA was identified in 41 of the 43
      cases (95.3%). HBV DNA was distributed generally in the nucleus and cytoplasm of
      epithelial cells and mesangial cells of glomeruli, and epithelial cells of renal
      tubules. HBV DNA also existed simultaneously in renal interstitial tissues in
      some of these cases. The positive results from HBV DNA ISH correlated well with
      HBV antigen assays. The analyses implied that the more extensive the existence of
      HBV DNA in the nephron unit and interstitial tissue, the more severe the clinical
      manifestation. The duration of proteinuria in cases with HBV DNA in renal tubules
      was much longer than in those with no HBV DNA in renal tubules. The persistence
      of the HBV genome or genes in the kidney could lead to the expression of viral
      antigens in renal tissues and might cause cellular pathological alteration. This
      would support utilization of antiviral therapy, such as cytokines, in the
      treatment of HBV-GN.

PMID- 9543369
TI  - Renovascular hypertension and vascular anomalies in Alagille syndrome.
AB  - Alagille syndrome (AS) is characterized by the association of at least three of
      the following five abnormalities: chronic cholestasis, peripheral pulmonary
      artery stenosis, vertebral arch defects, embryotoxon, and typical facies. In
      addition to urological abnormalities, tubulointerstitial nephritis, renal tubular
      acidosis, and mesangiolipidosis have been noted in AS. The usual manifestations
      of such renal pathologies rarely include hypertension. We report five patients
      with at least four of the five major features of AS who developed secondary
      hypertension of renovascular origin 3.5-28 years after the initial diagnosis of
      AS. Angiography demonstrated uni- or bilateral renal artery stenosis and various
      other abnormalities of the main arteries in all five patients: aorta (3 cases),
      celiac artery (4 cases), superior mesenteric artery (1 case), subclavian artery
      (1 case). Our findings underscore the value of arterial blood pressure monitoring
      in patients with AS. If hypertension occurs, a renovascular origin should be
      sought. The diffuse vascular abnormalities which appeared to be a feature of AS
      in these patients should prompt larger studies of vascular abnormalities in AS.

PMID- 9543370
TI  - Reference values for cystatin C serum concentrations in children.
AB  - Cystatin C, a low molecular weight protein, is a new endogenous marker of renal
      function whose serum concentration correlates better with glomerular filtration
      rate than creatinine. The aim of the present study was to define a reference
      interval for cystatin C concentrations in children. Cystatin C was measured by an
      immunoturbidimetric assay in sera obtained from 258 children (93 girls, 165 boys,
      median age 6.29 years, range 1 day to 18 years) without evidence of kidney
      disease. The reference interval was calculated non-parametrically using the 2.5th
      and 97.5th percentiles. For comparison, creatinine was measured in the same
      samples. The cystatin C concentration was highest on the first days of life
      (range 1.64-2.59 mg/l) with a rapid decrease during the first 4 months. Beyond
      the 1st year, the cystatin C concentration was constant, with a reference
      interval of 0.7-1.38 mg/l. In contrast, serum creatinine concentrations steadily
      increased with age until adulthood. Compared with creatinine, cystatin C
      facilitates the recognition of abnormal renal function in children as its
      reference range is constant beyond the 1st year of life. The higher levels of
      cystatin C in the 1st year of life probably reflect the low glomerular filtration
      rate of neonates and infants.

PMID- 9543371
TI  - Adequate clinical control of congenital nephrotic syndrome by enalapril.
AB  - The combination of captopril and indomethacin has been shown to control nephrotic
      proteinuria in an infant with congenital nephrotic syndrome of the Finnish type.
      We report the satisfactory control of congenital nephrotic syndrome by enalapril,
      maintaining normal serum albumin levels without albumin infusions. The haplotype
      data of our patient were consistent with the diagnosis of a Finnish-type
      nephrotic syndrome. After 21 months, during which daily infusions of albumin
      allowed partial control of the symptoms, captopril treatment was started. No
      adverse effects were noted. Serum creatinine levels remained normal. Within 8
      weeks, albumin infusions were completely stopped. After 1 month the treatment was
      changed to a single dose of enalapril (0.8 mg/kg per day). During the next 15
      months, the serum protein concentration was maintained around 6.5-7 g/dl,
      although proteinuria persisted (0.3-0.5 g/day). Weight and length gain are now
      satisfactory. We conclude that enalapril may be safely used in infants with
      severe forms of congenital nephrotic syndrome and might allow the avoidance of
      aggressive treatments for prolonged periods.

PMID- 9543372
TI  - Subclinical activation of lupus nephritis by recombinant human growth hormone.
AB  - The effect of growth hormone (GH) on subclinical disease activity in a 15-year
      old boy with previously quiescent lupus nephritis and chronic renal failure is
      described. Institution of supraphysiological doses of GH resulted in a rise in
      erythrocyte sedimentation rate, decrease in serum complement, rise in anti-DNA
      antibody titers, and increase in T-cell activation markers, all of which improved
      following cessation of GH treatment.

PMID- 9543373
TI  - Remission of infantile systemic lupus erythematosus with intravenous
      cyclophosphamide.
AB  - We report an 8-month-old boy with systemic lupus erythematosus and World Health
      Organization class IV lupus nephritis who has gone into complete clinical and
      serological remission with pulse i.v. cyclophosphamide therapy. To our knowledge
      this is the first case of pulse i.v. cyclophosphamide therapy in infantile
      systemic lupus erythematosus resulting in long-term remission.

PMID- 9543374
TI  - Chronic interstitial cystitis and systemic lupus erythematosus in an 8-year-old
      girl.
AB  - An 8-year-old girl with systemic lupus erythematosus (SLE) and diffuse
      proliferative glomerulonephritis had chronic interstitial cystitis (CIC) early in
      the course of SLE. The early occurrence of CIC, the lack of intestinal symptoms,
      the association with vesicoureteric reflux, and the improvement of CIC during
      therapy with cyclosporin A were the prominent features of the patient reported
      here.

PMID- 9543375
TI  - Coexistence of VATER association and recurrent urolithiasis: a case report.
AB  - VATER association is diagnosed by the combined presence of at least three of the
      following features: vertebral anomalies, anal atresia, tracheo-esophageal fistula
      and/or esophageal atresia, radial ray anomalies, and renal anomalies (53%).
      Urolithiasis has not been reported in this syndrome. A 4-month old girl presented
      because of irritability, and the presence of stones in the diapers. Physical
      examination revealed anal atresia for which colostomy was performed in the
      newborn period. The diagnosis of VATER association was established by the
      additional findings of hemivertebrae, sacral dysgenesis, and horseshoe kidney
      which was partly non-functional. Urinary pH was repeatedly below 6. An excreted
      stone consisted of pure uric acid. Metabolic investigations detected no specific
      pathology in purine metabolism. Urolithiasis did not recur after reconstructive
      anal and anorecto-vaginoplasty, implying that it was a consequence of colostomy
      and/or of the underlying renal anomaly. We suggest that after colostomy patients
      with VATER association should be followed for possible urate stones, e.g. by
      regular screening of urinary pH.

PMID- 9543376
TI  - Nephrocalcinosis in three siblings with idiopathic hypercalciuria.
AB  - Idiopathic hypercalciuria (IH) associated with nephrocalcinosis was found in
      three of six siblings. After the three affected children were maintained on a low
      calcium diet, they demonstrated increasing hypercalciuria, parathyroid hormone,
      and vitamin D3 levels. An oral calcium loading test was not necessary to diagnose
      renal IH. During treatment with hydrochlorothiazide, the calcium excretion was
      normalized. These patients are remarkable because nephrocalcinosis is generally
      regarded as a rare complication of renal IH. Moreover, the fact that three of six
      siblings are affected raises the question of whether the renal form of IH is
      genetically distinct from other forms of IH.

PMID- 9543377
TI  - Sedation with intravenous benzodiazepine and ketamine for renal biopsies.
AB  - "Lytic cocktail" is the customary sedation before percutaneous renal biopsy.
      Owing to deficient sedation and respiratory depression, this approach is no
      longer advised. The intravenous combination of a benzodiazepine plus ketamine,
      which has been found to be effective and safe in several conditions, was
      therefore used for 60 pediatric biopsies. In addition to pulse oximetry, a
      physician trained in airway management monitored the patient. The quality of
      sedation was acceptable (n = 7) or optimal (n = 53) in all cases. None of the
      patients required ventilation or intubation. A mild oxygen desaturation lasting 4
      min or less was detected in 6 patients. None of the patients experienced major
      change in respiratory rate or blood pressure. The administration of ketamine and,
      in some cases, the biopsy puncture were associated with a mildly increased heart
      rate. In conclusion, a benzodiazepine plus ketamine provides effective deep
      sedation for renal biopsy in childhood.

PMID- 9543378
TI  - Evaluation of perioperative antibiotics at the time of dialysis catheter
      placement.
AB  - The effect of prophylactic antibiotics on the occurrence of peritonitis in the 14
      days following surgical peritoneal dialysis catheter placement was evaluated.
      Medical records from 73 pediatric patients who had 89 Tenckhoff catheters
      inserted over 6 years were reviewed. Twelve catheter procedures were excluded for
      rapid catheter loss, unavailable charts, eosinophilic peritonitis, and antibiotic
      administration > 3 h postoperatively. Chi-squared analysis for non-continuous
      variables compared factors at the time of catheter placement with outcome
      (peritonitis). Thirteen patients developed postoperative peritonitis when 77
      catheter insertions were analyzed (17%). Peritonitis was significantly more
      common in patients who did not receive perioperative antibiotics (7 of 16
      catheter placements) (chi(2) = 12.48, P < or = 0.001). The reduced incidence of
      peritonitis was not specific to any one antibiotic class. Using step-wise
      logistic regression analysis, no association was found between peritonitis
      incidence and nephrotic syndrome, immunosuppression, recent surgery (< 14 days),
      acute versus chronic use, year of catheter placement, surgeon, or patient age.
      Catheter type, implantation technique, exit site care, and operative wound care
      did not vary. These results indicate that perioperative peritonitis episodes can
      be significantly reduced by the use of prophylactic antibiotics prior to or at
      the time of surgery.

PMID- 9543379
TI  - Acute changes in endothelin after hemodialysis in children.
AB  - The purpose of this study was to investigate the acute changes in endothelin (ET)
      levels immediately after hemodialysis and to determine whether these changes vary
      with the use of different membranes and hemodialysis solutions. Ten children were
      included in the study. Three different hemodialysis sessions were performed on
      all patients: session 1, acetate-based dialysate and polycarbonate membrane;
      session 2, bicarbonate-based dialysate and polycarbonate membrane; session 3,
      acetate-based dialysate and polysulfone membrane. In all cases blood samples were
      obtained before and after dialysis. Pre- and post-hemodialysis ET levels of the
      patients with acetate-based dialysate and polycarbonate membrane were 33.68 +/-
      11.51 pg/ml and 28.27 +/- 12.85 pg/ml, respectively. The fall in ET levels after
      this session was statistically significant (P = 0.015). We did not observe a
      statistically significant change in ET levels in the other sessions. Post
      dialysis mean arterial pressure values were significantly lower than the pre
      dialysis values in all three dialysis sessions (P < 0.01). A positive correlation
      was observed between plasma ET levels and blood urea nitrogen and serum
      potassium; a negative correlation was observed between plasma ET levels and
      hematocrit.

PMID- 9543380
TI  - Growth hormone and renal osteodystrophy: a case report.
AB  - A 14-year-old male with end-stage renal disease on hemodialysis was treated with
      recombinant growth hormone for growth retardation. He developed severe renal
      osteodystrophy, which responded only to the discontinuation of growth hormone.

PMID- 9543381
TI  - A bridge over troubled water...mixed water and electrolyte disorders.
AB  - Plasma volume, nitrogenous wastes in the plasma, and plasma osmolality profoundly
      affect the function of various organs in the body, particularly the central
      nervous system and the heart. Some parameters are more critical for these organs
      than others, so that, when homeostatic mechanisms come into play, the body often
      defends the parameter of greatest importance at the expense of others. The
      hyponatremia and azotemia that develop in dehydrated infants exemplify this
      prioritization of the body. The primary goal of therapeutic intervention in such
      circumstances is, therefore, geared toward a correction of dehydration. While
      alterations in plasma and urinary electrolyte patterns commonly reflect
      adjustments made by the body's machinery, it is essential at the bedside to
      identify factitiously abnormal laboratory results produced by laboratory
      analytical machines. They measure not only biologically active but also
      insignificant components of plasma electrolytes and osmolality.

PMID- 9543382
TI  - Hyposensitization is contraindicated in Hymenoptera venom-allergic children
      treated with cyclosporin.

PMID- 9543383
TI  - Additional cases of ureteral obstruction associated with Henoch-Schonlein
      purpura.

PMID- 9543384
TI  - More on ureteral obstruction associated with Henoch-Schonlein purpura.

PMID- 9543385
TI  - Which antibiotics must I use to treat acute pyelonephritis in an oligoanuric
      child?

PMID- 9543386
TI  - C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3
      3 protein binding.
AB  - Cdc25C is a dual-specificity protein kinase that controls entry into mitosis by
      dephosphorylating Cdc2 on both threonine 14 and tyrosine 15. Cdc25C is
      phosphorylated on serine 216 throughout interphase but not during mitosis. Serine
      216 phosphorylation mediates the binding of 14-3-3 protein to Cdc25C, and
      Cdc25C/14-3-3 complexes are present throughout interphase but not during mitosis.
      Here we report the cloning of a human kinase denoted C-TAK1 (for Cdc twenty-five
      C associated protein kinase) that phosphorylates Cdc25C on serine 216 in vitro. C
      TAK1 is ubiquitously expressed in human tissues and cell lines and is distinct
      from the DNA damage checkpoint kinase Chk1, shown previously to phosphorylate
      Cdc25C on serine 216. Cotransfection of Cdc25C with C-TAK1 resulted in enhanced
      phosphorylation of Cdc25C on serine 216. In addition, a physical interaction
      between C-TAK1 and Cdc25C was observed upon transient overexpression in COS-7
      cells. Finally, coproduction of Cdc25C and C-TAK1 in bacteria resulted in the
      stoichiometric phosphorylation of Cdc25C on serine 216 and facilitated 14-3-3
      protein binding in vitro. Taken together, these results suggest that one function
      of C-TAK1 may be to regulate the interactions between Cdc25C and 14-3-3 in vivo
      by phosphorylating Cdc25C on serine 216.

PMID- 9543387
TI  - Rac1 and extracellularly regulated kinase activation are sufficient for E1A
      dependent cooperative transformation of primary epithelial cells, but progression
      can only be modulated by E1A or Rac1.
AB  - Ras transformation of fibroblast cell lines requires activation of multiple
      distinct signal pathways that act synergistically. E1A-ras cotransformation of
      primary epithelial cells is enhanced by distinct mutations in the second exon of
      E1A, resulting in "hypertransformation" and metastasis. The molecular and
      cellular differences in the in vitro properties of such transformed cells are
      characterized here. Hypertransformed cells grew faster and to higher saturation
      densities; had smaller, more refractile cell morphologies with pronounced actin
      microspikes; and were less adhesive when compared with wild-type (WT) E1A+ras
      expressing cells. No significant differences were observed in extracellularly
      regulated kinase activity levels between the hypertransformed and WT transformed
      cells. Activated raf and Rac1 together were sufficient for transformation of
      primary epithelial cells with E1A, whereas neither alone was competent to
      cooperate with E1A. In the presence of activated ras and WT E1A, activated Rac1
      expression effected all of the hypertransformation properties. Dominant-negative
      Rac1 expression was suppressive of the hypertransformation phenotype, including
      cell morphology, actin cytoskeletal structures, decreased growth rates, and
      increased adhesion. Thus, hypertransformation is not the result of
      extracellularly regulated kinase differences but can be effected by perturbations
      in Rac1 signals, as well as E1A 12S COOH-terminal mutants.

PMID- 9543388
TI  - FKBP12 is not required for the modulation of transforming growth factor beta
      receptor I signaling activity in embryonic fibroblasts and thymocytes.
AB  - Transforming growth factor beta (TGF-beta) signals through a heteromeric complex
      of type I and type II transmembrane serine-threonine kinases. Recent evidence
      suggests that the immunophilin FKBP12 modulates the activity of the type I
      receptor, based on data that immunosuppressive drugs that disrupt FKBP12 binding
      to the type I receptor enhance TGF-beta signaling in mink lung epithelial cells,
      and overexpression of FKBP12 inhibits type I receptor phosphorylation by the type
      II receptor. To determine the physiological relevance of the FKBP12-TGF-beta
      receptor I interaction, we investigated whether disruption of this interaction
      affects TGF-beta-signaling in primary mouse embryo fibroblasts and thymocytes. We
      found that the addition of excess drugs had no effect on either TGF-beta-mediated
      transcriptional responses or growth inhibition. Dose-response curves for TGF-beta
      mediated signaling in primary fibroblasts and thymocytes isolated from either
      wild-type or FKBP12-deficient mice were identical. Taken together, our results
      indicate that FKBP12 does not play a unique physiological role in TGF-beta
      signaling in primary fibroblasts and thymocytes.

PMID- 9543389
TI  - Dominant-negative interference of the transforming growth factor beta type II
      receptor in mammary gland epithelium results in alveolar hyperplasia and
      differentiation in virgin mice.
AB  - Transforming growth factor (TGF)-beta1 and TGF-beta3 are normally expressed at
      high levels in the mammary gland during quiescence and at all stages of
      development, except lactation. Exogenously added TGF-beta1, -beta2, and -beta3
      have been shown to regulate growth and differentiation of mammary epithelial
      cells in vitro and in vivo. TGF-betas signal through a heteromeric complex of
      type I and type II serine/threonine kinases. The type II receptor is necessary
      for ligand binding and growth suppression by TGF-betas. Deletions of the
      cytoplasmic domains of several kinase receptors known to function in multimeric
      complexes have been shown to act as dominant-negative mutations. To evaluate the
      role of endogenous TGF-betas in the growth and differentiation of the mammary
      gland in vivo, we have targeted expression of a truncated, kinase-defective TGF
      beta type II receptor to mammary epithelial cells in transgenic mice using the
      mouse mammary tumor virus promoter/enhancer. Transgene expression was localized
      to the epithelial cells of terminal ducts and alveolar buds. At approximately 20
      weeks of age, virgin female transgenic mice demonstrated varying degrees of
      mammary epithelial hyperplasia. Mammary glands from transgenic, virgin animals
      exhibited alveolar development and expression of the milk protein, beta-casein.
      The data suggest that impaired responsiveness in the epithelium to endogenous TGF
      betas results in inappropriate alveolar development and differentiation in the
      mammary gland. We conclude that endogenous TGF-betas signal to the epithelium to
      maintain quiescence in the mammary glands of virgin animals.

PMID- 9543390
TI  - Effects of endothelial nitric oxide synthase gene expression on the tumor biology
      of human oral carcinoma SCC-25 cells.
AB  - Stable transfection of endothelial nitric oxide synthase (eNOS) cDNA in human
      oral carcinoma SCC-25 cells was performed. Two eNOS-expressing clones were
      isolated, and both were shown to have increased eNOS expression as assayed by
      Northern and Western analyses. Furthermore, a nitrite assay indicated that nitric
      oxide production in eNOS-transfected cells was increased. The growth rate and
      plating efficiency of eNOS-transfected cells in vitro were lower than that of the
      wild-type parental or vector control-transfected cells as assayed by growth
      curves, [3H]thymidine incorporation, and standard plating efficiency assays in L
      arginine-rich medium. However, when these cancer cells were inoculated into nude
      mice, tumor size of eNOS-transfected cells was smaller during the first 25 days
      but increased later as compared to tumor size of parental and vector control
      transfected cells. It is not clear whether the later increase in tumor size was
      due to an increase in SCC-25 cancer cell proliferation, normal stromal cell
      proliferation, or both. These results show significant effects of overexpression
      of eNOS on tumor growth in vitro and in vivo.

PMID- 9543391
TI  - Activation of phosphatidylinositol 3-kinase is necessary for differentiation of
      FDC-P1 cells following stimulation of type III receptor tyrosine kinases.
AB  - Signaling molecules that are responsible for proliferation and differentiation of
      hematopoietic cells following ectopic expression of receptor tyrosine kinases
      (RTKs) were investigated in the interleukin 3 (IL-3)-dependent hematopoietic cell
      line, FDC-P1. Cells were transfected with human platelet-derived growth factor
      receptor (PDGF-R), macrophage colony stimulating factor-1 receptor (CSF-1R),
      epidermal growth factor receptor (EGF-R), and chimeras consisting of the
      extracellular domain of EGF-R and the transmembrane and cytoplasmic domains of
      either HER2 (HER1-2) or c-kit (EK-R). All FDC-P1 transfectants proliferated in
      response to the corresponding growth factor in the absence of IL-3. However, only
      cells expressing PDGF-R, CSF-1R, and EK-R (type III RTKs) differentiated along
      the monocyte-macrophage lineage after treatment with their activating ligands.
      Analysis of proteins from these RTK-expressing cells revealed that a Mr 85,000
      protein showed in vitro phosphorylation, and V8 protease peptide mapping showed
      that this protein was p85, the regulatory subunit of phosphatidylinositol 3
      kinase (PI3-kinase). Accordingly, activation of PDGF-R-, CSF-1R-, and EK-R
      expressing cells led to an increase in PI3-kinase activity. Expression of EK-R
      mutant Y721F, which lacked the known p85 binding site, blocked differentiation
      and activation of PI3-kinase, without affecting proliferation. Last, addition of
      wortmannin to cells expressing PDGF-R, CSF-1R, and EK-R blocked ligand-induced
      differentiation in a concentration-dependent manner, and this effect correlated
      with wortmannin's ability to inhibit PI3-kinase. Thus, ectopic expression of both
      type I and III RTKs could stimulate FDC-P1 proliferation in the absence of IL-3;
      however, only activation of type III RTKs led to differentiation via selective
      coupling to p85 and PI3-kinase activation.

PMID- 9543392
TI  - Negative regulation of the rat cdc2 promoter in G1 by the silencer element.
AB  - Expression of the cdc2 gene is induced steeply at the G1-S-phase boundary. The
      previous analysis of promoter elements that confer inducibility revealed the
      enhancer at positions -276 to -265. Enhancer activity is suppressed by the
      upstream sequence that seems to contain the silencer. The silencer element was
      analyzed by fusing several oligonucleotides covering the silencer region upstream
      of the enhancer in the cdc2 promoter-luciferase construct. Oligonucleotide IV,
      which suppressed enhancer activity, was further dissected by the introduction of
      base substitutions and by forming the DNA-protein complexes with quiescent rat
      cell extract. The silencer element, AAGTAGTAAAAATA, was finally identified at
      positions -374 to -360, which resembles the enhancer sequencer but contains extra
      internal AG residues. Silencer complexes were formed with the quiescent cell
      extract, whereas the amounts of the complexes decreased with the progression of
      the cell cycle, and nearly no complexes were formed with the late G1 cell
      extracts. Conversely, the enhancer complex begins to be formed after late G1.
      Among the three silencer complexes, the formation of the slowest-migrating
      complex (complex III) was inhibited by the enhancer sequence, suggesting that a
      common factor interacts with both the silencer and enhancer. These results
      suggest that the conversion of complex formation from the silencer to the
      enhancer site regulates the induction of cdc2 promoter activity at the G1-S-phase
      boundary.

PMID- 9543393
TI  - Induction of the nuclear orphan receptor RORgamma during adipocyte
      differentiation of D1 and 3T3-L1 cells.
AB  - Here, we analyzed the expression of the three members of the retinoid-like orphan
      receptor (ROR) nuclear receptor subfamily during adipocyte differentiation.
      RORalpha and RORgamma mRNA were upregulated during adipocyte differentiation in
      preadipocyte D1 and 3T3-L1 cells, whereas RORbeta mRNA could not be detected. The
      induction of RORalpha and RORgamma mRNA succeeded the induction of peroxisome
      proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding
      protein alpha and occurred at a similar time interval as did the increase in aP2
      and lipoprotein lipase mRNA. Like the expression of PPARgamma and aP2, the
      induction of RORgamma mRNA was repressed by tumor necrosis factor alpha and
      transforming growth factor beta. The induction of adipogenesis by prostaglandin
      D2 and two thiazolidinediones in the multipotent stem cells C3H10T1/2 was also
      accompanied by an induction in RORgamma mRNA. In contrast to parental cells,
      clofibrate induces adipogenesis and RORalpha and RORgamma mRNA in BALB/c3T3 cells
      that ectopically express PPARgamma. RORgamma mediates its effect on transcription
      through specific response elements. Cotransfection of RORalpha or RORgamma and
      (RORgamma response element)4-chloramphenicol acetyltransferase into preadipocyte
      D1 cells induced transactivation of chloramphenicol acetyltransferase about 100
      fold, suggesting that ROR plays a role in the regulation of gene expression in
      adipocytes. The nuclear orphan receptor Rev-ErbAalpha, which did not exhibit
      transactivation function, was able to inhibit transactivation by RORgamma at two
      different levels. Our results show that RORgamma is induced during adipocyte
      differentiation in D1 and 3T3-L1 cells and functions as an active transcription
      factor, suggesting a role for RORgamma in the regulation of gene expression
      during this differentiation process.

PMID- 9543394
TI  - Problems associated with the Z-fold region of defibrillation electrodes.
AB  - To examine performance failures of automatic external defibrillator (AED) self
      adhesive electrodes, a retrospective analysis of patient reports and electrodes
      was conducted in a suburban emergency medical service (EMS) system. In all cases,
      only records from out-of-hospital cardiac arrests (OHCA) were used if the EMS was
      activated and an AED was used. Electrode failures were assessed as follows: 1)
      EMS staff returned defibrillation electrodes when they were unable to resolve
      repeated "Check Electrode" messages, and 2) an audit of selected records was used
      to determine the frequency of electrode problems during calls. Of 302 OHCA calls
      during the study period, 22 (7%) resulted in returned electrodes. Defects (cracks
      or faults) in the internal conductor were present in 37 (86%) of the 43 returned
      electrodes; 2 (5%) possessed dehydrated conductive gel, and in 4 (9%) electrodes
      no faults could be identified. Of the 21 complete sets of defective electrodes,
      16 (76%) had faults in both electrodes. Chart review revealed at least one "check
      electrode" message occurring in 21 (60%) of 35 OHCA reports. The electrode checks
      were present for a total of over 83 min, representing 11% of the call times.
      Paramedics were required to change electrodes in 9 (26%) of the 35 cases,
      resolving the malfunction in all instances. Electrode malfunction appears to be a
      common prehospital problem; the conductor is responsible for the majority of
      electrode problems and is probably subjected to the most stress during storage
      and handling. More reliable, durable defibrillation electrodes are required for
      OHCA treatment. Other strategies for electrode storage and quality control are
      also discussed.

PMID- 9543395
TI  - Case report of an unusual source of tetanus.
AB  - We report a case of generalized tetanus in a 31-year-old male originating from a
      surgical wound after repair of an achilles tendon rupture. Our case illustrates
      an unusual source of tetanus, the need for tetanus prophylaxis before surgery,
      and the importance of asking about primary tetanus immunization, particularly in
      immigrants.

PMID- 9543396
TI  - Facial injury and airway threat from inhalant abuse: a case report.
AB  - Fluorinated hydrocarbons cause toxicity in humans via their dysrhythmogenic
      potential and their local physical effects on the skin and mucous membranes. The
      former is generally the more life-threatening toxic consequence. We present a
      case of fluorinated hydrocarbon injury resulting from an intentional inhalation
      exposure that created facial frostbite, which threatened the patient's airway.
      The clinical range and management of these tissue-toxic effects are reviewed.

PMID- 9543397
TI  - Heavy metal toxicity, part II: lead and metal fume fever.
AB  - This review is the second of a two-part review of heavy metal toxicity. This part
      will identify the salient features of the toxicopathophysiology, clinical
      presentation, and emergency department management of lead toxicity and metal fume
      fever.

PMID- 9543398
TI  - Missed cervical dissociation--recognizing and avoiding potential disaster.
AB  - Complete cervical disruptions are high-energy injuries often associated with
      polytrauma and spinal cord injury. Because these injuries disrupt all anterior
      and posterior stabilizers, they result in a highly unstable spine, and the
      injuries are usually apparent on screening radiographs. Patients with these
      injuries must be identified and protected during the multiple diagnostic and
      surgical procedures they may require during their initial evaluation and
      treatment. Emergency procedures must be carefully prioritized relative to other
      life-threatening injuries; formal evaluation of the cervical spine may be carried
      out before, after, or in stages around other urgently indicated procedures. Until
      the cervical spine is cleared, careful observation of precautions can avoid
      disasterous complications in even the most unstable situation. A case of complete
      cervical disruption in a neurologically intact, hemodynamically unstable patient
      is presented for discussion. For polytraumatized patients with cervical
      dissociation, combined anterior and posterior stabilization is the treatment of
      choice.

PMID- 9543399
TI  - Lacerations against Langer's lines: to glue or suture?
AB  - This study evaluated the effects of initial wound orientation on the cosmetic
      outcome of facial lacerations repaired with histoacryl blue (HAB), a tissue
      adhesive, vs. conventional suturing. This was a retrospective analysis of
      patients from a prospective randomized clinical trial on the use of HAB. Children
      in the initial cohort who had facial lacerations and were also evaluated for
      cosmetic appearance at a 2-month follow-up appointment were eligible. Orientation
      along Langer's Lines, which define the functional anatomy of the underlying
      structures to the skin, was determined by two investigators blinded to the
      initial method of repair. Photographs of the wounds were reviewed and the wounds
      were categorized as being: Langer (+) (<20 degrees deviated from Langer's Lines)
      or Langer (-) (> or =20 degrees deviated from Langer's Lines). Photographic
      appearance at follow-up was evaluated using a 100-mm visual analog scale (0=best,
      100=worst) by two plastic surgeons blinded to the method of repair. Sixty-one
      patients were enrolled in the initial cohort, with 55 (90%) evaluated at the 2
      month follow-up. Forty-eight of the 55 (87%) had facial lacerations, therefore
      meeting present study criteria: [HAB (n=26), Suturing (n=22), Langer (+) (n=27),
      Langer (-) (n=21)]. Langer (+) patients were comparable to Langer (-) for
      demographics, wound characteristics, and method of repair. There was no
      difference in overall cosmetic appearance of facial wounds closed with HAB vs.
      conventional suturing. Follow-up appearance was significantly worse for sutured
      Langer (-) vs. Langer (+) wounds. In contrast, cosmetic appearance of lacerations
      closed by HAB were comparable between Langer (-) and Langer (+) wounds. In
      conclusion, initial wound orientation had a greater impact on the cosmetic
      appearance for lacerations closed by suturing compared to HAB. HAB may be the
      preferred method of cutaneous closure for facial lacerations oriented against
      Langer's Lines.

PMID- 9543400
TI  - Parenteral hydralazine revisited.
AB  - Historical aspects of the development and application of the vasodilator
      hydralazine are reviewed. The pharmacology, pharmacokinetics, metabolism, and
      mechanism of action are discussed, with emphasis on the parenteral use of this
      drug. It is reiterated that parenteral hydralazine is the preferred drug for the
      treatment of severe preeclampsia, but its usefulness in other forms of
      accelerated hypertension is also addressed. Through comparisons with other
      established antihypertensive agents, the efficacy and pharmacoeconomic potential
      of hydralazine are stressed.

PMID- 9543401
TI  - A close look at fenfluramine and dexfenfluramine.
AB  - In an effort to combat obesity, several medications have been developed. The
      nonamphetamine anorectics, such as phentermine, fenfluramine, and
      dexfenfluramine, have been recommended as first-line drug therapy for the
      treatment of obesity once diet and exercise alone have failed. Numerous studies
      have shown that these agents can promote weight loss when combined with diet
      restriction and exercise. Although fenfluramine and dexfenfluramine lack the
      abuse potential of amphetamine and its congeners, these agents are associated
      with drug interactions and adverse effects. Concomitant administration of
      fenfluramine or dexfenfluramine with medications that enhance serotonin levels
      (e.g., antidepressants, monoamine oxidase inhibitors, and migraine medications)
      can precipitate serotonin syndrome. Sudden discontinuation of fenfluramine or
      dexfenfluramine after prolonged administration can precipitate withdrawal
      depressive symptoms. Primary pulmonary hypertension, a potentially fatal
      disorder, has been reported to occur approximately 30 times more frequently in
      patients receiving anorectic agents for more than 3 months compared to the
      general population. More recently, the association of these popular anorectics
      with valvular heart disease has caused increased concerns about their use. The
      risks of primary pulmonary hypertension, valvular heart disease, and the
      occurrence of convulsions, coma, and death in overdose appear to be equally
      likely with dexfenfluramine and fenfluramine. In addition, many patients who lose
      weight while taking these anorectics rapidly regain it after the medication has
      been discontinued.

PMID- 9543402
TI  - High-speed motor vehicle crash.

PMID- 9543403
TI  - Erythema multiforme major.

PMID- 9543404
TI  - Cost-effective medicine: the financial impact that practice guidelines have on
      outpatient hospital charges in the emergency department.
AB  - The objective of this study was to determine whether specific cost-effective
      guidelines based on a patient's chief complaint can significantly reduce
      outpatient hospital charges in the ED. A prospective randomized single-blinded
      clinical trial was conducted in an urban community hospital ED with a 14,000
      annual census. The first phase of the study involved preintervention data
      collection. The second phase focused on development, physician approval, and
      implementation of 23 specific cost-effective guidelines, as well as general
      recommendations for diagnostic tests. The third phase involved postintervention
      data collection. Results showed that the total outpatient hospital charge
      decreased by 28% per patient. The laboratory hospital charge decreased by 46% per
      patient. The radiology hospital charge decreased by 20% per patient. The hospital
      supply charge and pharmacy charge decreased by 31% per patient and 11% per
      patient, respectively. In conclusion, cost-effective medicine practiced with
      specific guidelines, based on a patient's chief complaint, significantly reduces
      unnecessary diagnostic tests and medical treatments ordered by emergency
      physicians.

PMID- 9543405
TI  - The duality of medicine: reaching a balance.

PMID- 9543406
TI  - "Black plaque" on the Internet.

PMID- 9543407
TI  - Pneumothorax following acupuncture is a generally recognized complication seen by
      many emergency physicians.

PMID- 9543408
TI  - Against customer service.
AB  - This essay examines the nature of service in medicine and the relationship
      between service and profit. "Customer service medicine" is identified with the
      interrelated views that 1) profit is or ought to be healthcare's fundamental
      concern and 2) the quality of medical service corresponds to the degree to which
      it produces a feeling of approval in patients. This position is contrasted with
      the more traditional "beneficence model," which holds that 1) service ought to be
      healthcare's fundamental concern and 2) the proper criterion of quality medical
      service is the alleviation, mitigation, or prevention of the human suffering that
      occasions illness. Five shortcomings in the customer service model are
      identified: 1) customer service advocates often appeal to an unsound "efficiency
      argument"; 2) the prioritization of profit over service will vitiate patients'
      legitimate trust in healthcare; 3) the prioritization of profit converts medicine
      from a "practice" into an "instrumental activity"; 4) the prioritization of
      profit countervails the values of continuity and thoroughness; and 5) the notion
      of service as customer satisfaction derives more from the exigencies of turning a
      profit than from an analysis of sick persons' needs.

PMID- 9543409
TI  - Guidelines for red blood cell and plasma transfusion for adults and children: an
      emergency physician's overview of the 1997 Canadian Blood Transfusion Guidelines.
      Part 2: Plasma transfusion and infectious risk.

PMID- 9543410
TI  - Physician services in small and rural emergency departments: a critique of the
      Scott Report.

PMID- 9543411
TI  - Imaging asynchronous mechanical activation of the paced heart with tagged MRI.
AB  - A method for imaging the rapid temporal-spatial evolution of myocardial
      deformations in the paced heart is proposed. High time resolution-tagged MR
      images were obtained after stimulation of the myocardium with an MR-compatible
      pacing system. The images were analyzed to reconstruct dynamic models of local 3D
      strains over the entire left ventricle during systole. Normal canine hearts were
      studied in vivo with pacing sites on the right atrium, left ventricular free wall
      and right ventricular apex. This method clearly resolved local variations in
      myocardial contraction patterns caused by ventricular pacing. Potential
      applications are noninvasive determination of electrical conduction abnormalities
      and the evaluation of new pacing therapies.

PMID- 9543412
TI  - Improved coverage in dynamic contrast-enhanced cardiac MRI using interleaved
      gradient-echo EPI.
AB  - An interleaved gradient-echo echo-planar imaging (IGEPI) sequence was modified
      for and applied to dynamic contrast-enhanced imaging of the heart. Using IGEPI,
      images with 3.0 x 3.9 mm nominal in-plane resolution are acquired in 100 ms,
      enabling eight slices per heartbeat for a heart rate of 60 beats/min. The
      acquisition speed and use of saturation prepulses allows acquisition of short-
      and long-axis images during the same contrast bolus. IGEPI maintains the
      acquisition characteristics required for performing a quantitative first-pass
      perfusion analysis as well as providing improved coverage compared with
      conventional fast gradient echo.

PMID- 9543413
TI  - Spatial and temporal differentiation of fMRI BOLD response in primary visual
      cortex of human brain during sustained visual simulation.
AB  - The blood oxygenation level dependent (BOLD) response during sustained visual
      stimulation has been studied by several groups using fMRI with controversial
      conclusions. This issue was investigated for the human brain at high (4 Tesla)
      magnetic field strength using a flashing goggle at 8 Hz. The results demonstrate
      that the overall BOLD response in the primary visual cortex has an initial
      overshoot after the onset of visual stimulation and an undershoot after the
      termination of visual stimulation. A significant and positive BOLD response,
      however, remains constant between the initial and terminal transient responses.
      The temporal BOLD responses in the primary visual cortex were spatially
      dependent. The regions identified as draining veins in images displayed
      proportionately larger initial and terminal transient responses, whereas regions
      devoid of such vessels and associated mainly with parenchyma exhibited a more
      time-independent BOLD response. These results reveal that the BOLD effect and,
      presumably, the uncoupling between cerebral blood flow and cerebral metabolic
      rate of oxygen consumption, are maintained in the primary visual cortex during
      sustained visual stimulation, and the temporal characteristics of the BOLD effect
      are spatially dependent.

PMID- 9543415
TI  - Sound generation in gradient coil structures for MRI.
AB  - When supporting plates of plastic material are subjected to alternating
      transverse Lorentz forces while in a strong magnetic field normal to the plate
      surface, compressional waves within the solid produce a modulation of the plate
      surface that launches an acoustic wave in air along the magnetic field axis. We
      have extended our previous theory describing this process to include a detailed
      description of the formation of an acoustic interference pattern in air described
      by Fraunhofer diffraction at a distance from the plate surface. The extended
      theory predicts that the observed acoustic signal midpoint and normal to the
      plate surface gives a variation with frequency in approximate agreement with our
      previous measurements. The acoustic output off axis shows acoustic blazing that
      produces two main diffraction peaks with a splitting inversely proportional to
      the velocity of sound in the plate material. The new results could have important
      ramifications for the minimization of sound output in gradient coil design for
      MRI. A new arrangement of coils is proposed to ameliorate the acoustic output
      problem centrally and normal to the plate by extending the frequency response of
      the supporting plates to much higher frequencies. Also presented are estimates of
      the compressional wave velocities deduced from frequency response data recorded
      at the center-point of a number of different plates.

PMID- 9543414
TI  - Multiple-echo proton spectroscopic imaging using time domain parametric spectral
      analysis.
AB  - A multiple-echo MR spectroscopic imaging (MRSI) method is presented that enables
      improved metabolite imaging in the presence of local field inhomogeneities and
      measurement of transverse relaxation parameters. Short echo spacing is used to
      maximize signal energy from inhomogeneously line-broadened resonances, and time
      domain parametric spectral analysis of the entire echo train is used to obtain
      sufficient spectral resolution from the shortened sampling periods. Optimal
      sequence parameters for 1H MRSI are determined by computer simulation, and
      performance is compared with conventional single-echo acquisition using phantom
      studies at a field strength of 4.7 T. A preliminary example for use at 1.5 T is
      also presented using phantom and human brain MRSI studies. This technique is
      shown to offer improved performance relative to single-echo MRSI for imaging of
      metabolites with shortened T2* values due to the presence of local field
      inhomogeneities. Additional advantages are the intrinsic measurement of
      metabolite T2 values and determination of metabolite integrals without T2
      weighting, thereby facilitating quantitative metabolite imaging.

PMID- 9543416
TI  - Simultaneous intracellular and extracellular pH measurement in the heart by 19F
      NMR of 6-fluoropyridoxol.
AB  - 6-Fluoropyridoxol (6-FPOL) was evaluated as a simultaneous indicator of
      intracellular and extracellular pH and, hence, pH gradient in perfused rat
      hearts. After infusion, 19F NMR spectra rapidly showed two well-resolved peaks
      assigned to the intracellular and extracellular compartments, and pH was
      calculated on the basis of chemical shift with respect to a sodium
      trifluoroacetate standard. To demonstrate use of this molecule, dynamic changes
      in myocardial pH were assessed with a time resolution of 2 min during respiratory
      and metabolic alkalosis or acidosis and ischemia. For a typical heart,
      intracellular pH (pHi) = 7.14+/-0.01 and extracellular pH (pHe) = 7.52+/-0.02. In
      response to metabolic alkalosis, pHi remained relatively constant and the pH
      gradient increased. In contrast, respiratory challenge caused a significant
      increase in pHi. Independent measurements using pH electrodes and 31P NMR
      confirmed validity of the 19F NMR results.

PMID- 9543418
TI  - Quantitative measurements of cerebral blood flow in rats using the FAIR
      technique: correlation with previous iodoantipyrine autoradiographic studies.
AB  - Flow-sensitive alternating inversion recovery (FAIR) is a recently introduced MRI
      technique for assessment of perfusion that uses blood water as an endogenous
      contrast agent. To characterize the FAIR signal dependency on spin tagging time
      (inversion time (TI)) and to validate FAIR for cerebral blood flow (CBF)
      quantification, studies were conducted on the rat brain at 9.4 T using a
      conventional gradient-recalled echo sequence. The T1 of cerebral cortex and blood
      was found to be 1.9 and 2.2 s, respectively, and was used for CBF calculations.
      At short TIs (<0.8 s), the FAIR signal originates largely from vascular
      components with fast flows, resulting in an overestimation of CBF. For TI > 1.5
      s, the CBF calculated from FAIR is independent of the spin tagging time,
      suggesting that the observed FAIR signal originates predominantly from
      tissue/capillary components. CBF values measured by FAIR with TI of 2.0 s were
      found to be in good agreement with those measured by the iodoantipyrine technique
      with autoradiography in rats under the same conditions of anesthesia and arterial
      pCO2. The measured pCO2 index on the parietal cortex using the FAIR technique was
      6.07 ml/100 g/min per mmHg, which compares well with the pCO2 index measured by
      other techniques. The FAIR technique was also able to detect the regional
      reduction in CBF produced by middle cerebral artery occlusion in rats.

PMID- 9543417
TI  - Sodium TQF NMR and intracellular sodium in isolated crystalloid perfused rat
      heart.
AB  - The feasibility of monitoring intracellular sodium changes using Na triple
      quantum filtered NMR without a chemical shift reagent (SR) was investigated in an
      isolated rat heart during a variety of interventions for Na(i) loading. Perfusion
      with 1 mM ouabain or without K+ present in the perfusate for 30 min produced a
      rise of the Na TQF signal with a plateau of approximately 190% and approximately
      228% relative to the preintervention level, respectively. Stop-flow ischemia for
      30 min resulted in a TQF signal growth of approximately 147%. The maximal Na TQF
      signal increase of 460% was achieved by perfusion without K+/Ca2+, corresponding
      to an elimination of the Na transmembrane gradient. The observed values of Na NMR
      TQF growth in the physiological and pathological ranges are in agreement with
      reported data by other methods and have a linear correlation with intracellular
      sodium content as determined in this study by Co-EDTA method and by sucrose
      histidine washout of the extracellular space. Our data indicate that the increase
      in Na TQF NMR signal is determined by the growth of Na(i), and the extracellular
      Na contribution to the total TQF signal is unchanged at approximately 64%. In
      conclusion, Na TQF NMR without using SR offers a unique and noninvasive
      opportunity to monitor alterations of intracellular sodium. It may provide
      valuable insights for developing cardioprotective strategies and for observing
      the effects of pharmaceutical treatments on sodium homeostasis.

PMID- 9543419
TI  - Ultra-fast velocity imaging in stenotically produced turbulent jets using RUFIS.
AB  - A method for rapidly producing velocity images is presented. This sequence
      combines a modified bipolar gradient pulse to magnitude encode the velocity with
      the rotating ultra-fast imaging sequence (RUFIS) to image the encoded spins.
      Velocity encoding is done in 3 msec, and RUFIS acquires 32 projections in 8 msec.
      The method is applied to turbulent jets associated with a 75% stenosis in a 15-mm
      inner diameter glass pipe. Data is acquired upstream and downstream from the
      stenosis for Reynolds numbers from 560 to 3750. In addition, a robust method of
      reconstructing the unobserved short time region of a free induction decay is
      presented and incorporated into the image processing.

PMID- 9543420
TI  - Gradient characterization using a Fourier-transform technique.
AB  - This paper describes a technique for characterizing the gradient subsystem of a
      magnetic resonance (MR) system. The technique uses a Fourier-transform analysis
      to directly measure the k-space trajectory produced by an arbitrary gradient
      waveform. In addition, the method can be easily extended to multiple dimensions
      and can be adapted to measuring residual gradient effects such as eddy currents.
      Several examples of gradient waveform and eddy-current measurements are
      presented. Also, it is demonstrated how the eddy-current measurements can be
      parameterized with an impulse-response formalism for later use in system tuning.
      When compared to a peak-fitting analysis, this technique provides a more direct
      extraction of the k-space measurements, which reduces the possibility of analysis
      error. This approach also has several advantages as compared to the conventional
      eddy-current measurement technique, including the ability to measure very short
      time constant effects.

PMID- 9543421
TI  - Off-resonance proton T1rho dispersion imaging of 17O-enriched tissue phantoms.
AB  - Proton T1rho dispersion imaging is a recently described method for indirect
      detection of 17O. However, clinical implementation of this technique is hindered
      by the requirement for a high-amplitude spin-locking field (gammaB1 > 1 kHz) that
      exceeds current limitations in specific absorption rate (SAR). Here, a strategy
      is offered for circumventing high SAR in T1rho dispersion imaging of 17O through
      the use of low-amplitude off-resonance spin-locking pulses (gammaB1 < 300 Hz).
      Proton spin-lattice relaxation times in the off-resonance rotating frame were
      measured in H2(17)O-enriched tissue phantoms. On- and off-resonance T1rho
      dispersion imaging was implemented at 2 T using a spin-locking preparatory pulse
      cluster appended to a standard spin-echo sequence. On- and off-resonance
      dispersion images exhibited similar 17O-based image contrast. Magnetization
      transfer effects did not depend on 17O concentration and had no effect on image
      contrast. In conclusion, off-resonance proton T1rho dispersion imaging shows
      promise as a safe, sensitive technique for generating 17O-based T1rho contrast
      without exceeding SAR limitations.

PMID- 9543422
TI  - Concomitant magnetic-field-induced artifacts in axial echo planar imaging.
AB  - When a linear magnetic field gradient is used, spatially higher-order magnetic
      fields are produced to satisfy the Maxwell equations. It has been observed that
      the higher-order magnetic field produced by the readout gradient causes axial
      echo planar images acquired with a horizontal solenoid magnet to shift along the
      phase-encoding direction and lose image intensities. Both the shift and intensity
      reduction become increasingly severe as the slice offset from the isocenter
      increases. These phenomena are quantitatively analyzed, and good correlation
      between experiments and theory has been established. The analysis also predicts a
      previously unreported Nyquist ghost on images with very large slice offsets. This
      ghost has been verified with computer simulations. Based on the analysis, several
      methods have been developed to eliminate the image shift, the intensity
      reduction, and the ghost. Selected methods have been implemented on a commercial
      scanner and proved effective in removing these image artifacts.

PMID- 9543423
TI  - Effects of gradient anisotropy in MRI.
AB  - A gradient system is anisotropic if the impulse responses of at least two of the
      gradient channels, x, y, or z, differ from each other. Such an undesired
      condition may arise, for example, from differences between the gradient channels
      with respect to eddy currents or from unbalanced time delays in the electronic
      components. Depending on the degree of anisotropy, the actual gradient then
      deviates from the nominal, desired gradient under certain oblique orientations
      during the transient periods of gradient switching. The adverse consequence is
      degradation of image quality, such as distortion, ghosting, and blurring. In this
      paper, a theoretical analysis is given of the basic effects. Furthermore, the
      implications for the MRI process and possible correction methods are described.
      The effects of anisotropy are shown experimentally for echo-planar imaging and
      two-dimensional selective RF excitation with spiral gradient pulses.

PMID- 9543425
TI  - Asymmetric sampling along k(slice-select) in two-dimensional multislice MRI.
AB  - Reduction of the slice-select refocusing gradient in two-dimensional multislice
      imaging results in asymmetry of the k-space representation of collected data
      along the slice-select direction. Standard methods of partial Fourier
      reconstruction developed for other methods of asymmetric k-space sampling can be
      used to reconstruct these data with final through-plane resolution smaller than
      the collected slice thickness. This method can be used for reducing scan time in
      the same manner as asymmetric sampling in the phase-encoded direction. In
      addition, the reduced refocusing gradient reduces minimum TE and motion artifacts
      in the same manner as for asymmetric sampling in the frequency-encoded direction
      (fractional echoes). Results using a resolution phantom and a flow phantom
      illustrate these concepts.

PMID- 9543424
TI  - Dynamic functional imaging of relative cerebral blood volume during rat forepaw
      stimulation.
AB  - Dynamic measurements of regional changes in cerebral blood volume (CBV) were
      performed in rat models of hypercarbia and focal neuronal activation using T2
      weighted imaging after injection of an intravascular contrast agent with a very
      long blood half-life. Calculated percent CBV change during hypercarbia was
      consistent with literature results from other non-invasive modalities. Equivalent
      percent CBV increases were found using spin- and gradient-echo images, suggesting
      proportional changes in blood volume for capillaries and small veins. During
      electrical stimulation of rat forepaw, focal CBV response to stimulation (24+/
      4%) was significantly delayed relative to blood oxygen level dependent (BOLD)
      signal after both onset and cessation of stimulation. Poststimulus CBV decay was
      temporally consistent with the BOLD poststimulus undershoot. The use of exogenous
      agent increased the functional contrast-to-noise ratio relative to BOLD imaging
      by 5.7+/-1.3 at a magnetic field strength of 2 Tesla and 1.5+/-0.2 at 4.7 Tesla.

PMID- 9543426
TI  - On the nature and reduction of plaque-mimicking flow artifacts in black blood MRI
      of the carotid bifurcation.
AB  - Cardiac-gated black blood MRI of the carotid artery bifurcation in normal human
      subjects shows signal within the lumen suggesting wall thickening or
      atherosclerotic plaque. This signal was believed to be artifactual, arising from
      complex flow patterns present at the carotid bifurcation. Computer simulation of
      the hemodynamics and black blood multislice image acquisition in a model of the
      carotid bifurcation showed that these artifacts arise from spins recovering their
      signal within the slow, recirculating flow of the carotid bulb. The computed
      hemodynamics also suggested that these artifacts could be minimized or eliminated
      entirely by gating the acquisition of slices in the most artifact-prone region of
      the carotid bulb within a 250-ms window after peak systole. Application of these
      predictions to studies of normal volunteers showed that, in most cases, these
      flow artifacts in black blood MRI can be eliminated simply by altering the phase
      of the cardiac cycle to which the image acquisition is gated. The observation
      that the size and placement of the saturation slabs had little effect on these
      artifacts suggested that, in those cases in which recirculation persists
      throughout the cardiac cycle, either inversion-recovery or presaturation within
      the bulb itself would be required to suppress them.

PMID- 9543427
TI  - Calibration of the 1H decoupling field strength and experimental evaluation of
      the specific RF absorption rate in 1H-decoupled human 13C-MRS.
AB  - For patient safety in human 1H decoupled 13C-MRS, it is absolutely necessary to
      evaluate the specific RF absorption rate (SAR) of the tissue exposed to 1H
      frequency irradiation. With the use of surface coils, the local SAR at the body
      surface is of most concern due to the inherent RF field inhomogeneity. An
      empirical procedure to spatially calibrate the decoupler power level and to
      evaluate the local SAR at the body surface is described. For head, liver, muscle
      gastrocnemius, and muscle vastus lateralis, the SAR at the body surface was
      estimated for an 1H/13C double surface coil setup. Optimized duty cycle values
      obtained with this procedure show that broad-band 1H-decoupled 13C-MR
      spectroscopy is clinically feasible at 1.5 T for such a coil configuration within
      safety guidelines.

PMID- 9543428
TI  - Proton T2 relaxation of cerebral metabolites during transient global ischemia in
      rat brain.
AB  - Putative changes of metabolite T2 relaxation times were investigated before and
      after a 20-min period of global ischemia in rat brain in vivo (n = 10) using
      localized proton MRS at different echo times (2.35 T). Neither absolute T2
      relaxation times (TE = 20-270 ms) nor time courses of T2-weighted metabolite
      signals (TE = 135 ms) revealed statistically significant changes during the
      occlusion or early reperfusion relative to pre-ischemic baseline. These findings
      are in line with reports of relaxation changes at much later stages and further
      demonstrate that altered T2 relaxation is not a confounding factor in diffusion
      weighted long-TE proton MRS during early ischemic events.

PMID- 9543429
TI  - A localized double-quantum filter for the in vivo detection of brain glucose.
AB  - A double-quantum filter (DQF) sequence with PRESS localization was developed for
      in vivo detection of the glucose resonances in the 3.85-ppm region of the brain
      proton spectrum. The efficiency and spectral editing characteristics were studied
      in phantom and animal experiments. Approximately 45% detection efficiency was
      achieved at 4.7 T with TE = 68 ms. Since the efficiency of the DQF method is
      dependent on the relative phases of the RF pulses, a phase calibration procedure
      was used to correct for phase shifts induced by the spatial localization. In
      addition to detecting the 3.85-ppm glucose resonances with approximately 45%
      efficiency, the DQF sequence simultaneously detects 1.3-ppm lactate resonance
      with approximately 20% efficiency. The use of the DQF technique for
      simultaneously monitoring both the input and output of anaerobic glycolysis in
      the brain was demonstrated by detecting brain glucose and lactate in the same
      acquisition after iv injection of glucose followed by the induction of global
      ischemia.

PMID- 9543430
TI  - Improved sampling of myocardial motion with variable separation tagging.
AB  - A novel tagging method is introduced that increases the spatial resolution of
      estimates of myocardial radial thickening. The separation of adjacent parallel
      tag planes is customized to match the expected motion of specific regions of the
      heart wall. In regions in which the tags increase their separation over systole
      (radial thickening), the tag planes are placed close together at end diastole. In
      regions in which the tags decrease their separation over systole (circumferential
      shortening), the tags are placed farther apart so they remain detectable at end
      systole. With variable separation tagging (VTAG), parallel plane tagging can be
      used to obtain higher-resolution estimates of radial thickening and
      circumferential shortening simultaneously.

PMID- 9543431
TI  - Simultaneous multislice acquisition with arterial-flow tagging (SMART) using echo
      planar imaging (EPI).
AB  - Arterial spin tagging techniques have been used to image tissue perfusion in MR
      without contrast injection or ionizing radiation. Currently, spin tagging studies
      are performed primarily using single-slice imaging sequences, which are time
      consuming. This note reports a multislice echo-planar arterial spin tagging
      technique (Simultaneous Multislice Acquisition with aRterial-flow Tagging, or
      "SMART"). Multiband RF encoding (Hadamard) is used to provide simultaneous
      multislice acquisition capability for spin tagging techniques (such as echo
      planar imaging signal targeting with alternating radio frequency and flow
      sensitive alternative inversion recovery). The method is illustrated with a two
      slice pulse sequence that was implemented using the FAIR technique to generate
      two perfusion weighted images simultaneously. Compared with single-slice
      sequences, this two-slice sequence provided similar image quality, signal-to
      noise ratio, and twice the spatial coverage compared with the single-slice
      technique within the same scan time.

PMID- 9543432
TI  - FID-based lung MRI at 0.5 T: theoretical considerations and practical
      implications.
AB  - Pulse sequences based on FID signals and projection reconstruction (PR) were
      investigated for lung MRI at 0.5 T and evaluated for artifacts caused by: (1) k
      space mismapping due to either delay or distortion of the readout gradient
      waveform, (2) cardiac motion and pulsatile flow, and (3) respiratory motion.
      Nonstructured artifacts were described, simulated, and experimentally confirmed
      for the first time. Nonstructured artifacts did not impair the demonstration of
      structures of high signal-to-noise ratio (SNR) but generated quantitative errors
      in the image intensity analysis over the lung parenchyma. The use of FID-based PR
      techniques for lung MRI is not justified at 0.5 T.

PMID- 9543433
TI  - Time-course imaging of rat embryos in utero with magnetic resonance microscopy.
AB  - Magnetic resonance (MR) microscopy was used to noninvasively investigate the
      development of live rat embryos in utero. The difficulty in making sequential
      observations of a developing mammalian embryo has frustrated developmental
      biologists for many years. Most current technologies analyze normal and abnormal
      development by observing end point phenotypes (in fixed specimens) rather than
      investigating the live embryo. MR microscopy was adapted to allow rat litters to
      be scanned three times each (at 1- to 3-day intervals) and has produced images of
      live developing embryos. It was demonstrated that repeated anesthesia and imaging
      protocols produced no gross malformations in the rat pups that were subsequently
      delivered and observed. Three-dimensional projection encoding with phase
      rewinders produced isotropic [256(3)] image data sets in about 30 minutes with
      excellent tissue contrast arising from steady-state effects in the amniotic
      fluid.

PMID- 9543435
TI  - A clinically relevant HIV-1 subunit vaccine protects rhesus macaques from in vivo
      passaged simian-human immunodeficiency virus infection.
AB  - OBJECTIVES: To investigate whether immunization with recombinant HIV-1 envelope
      protein derived from a clinical isolate could protect macaques from infection
      with an in vivo passaged chimeric simian-human immunodeficiency virus (SHIV).
      DESIGN AND METHODS: A total of 16 animals were studied from which three groups of
      four animals were immunized with vaccine formulations of the CC-chemokine
      receptor-5-binding recombinant gp120 of HIV-1W6.1D. Four weeks after the last
      immunization, all 16 animals were intravenously challenged with in vivo passaged
      SHIV derived from the same HIV-1 group B clinical isolate (W6.1D) as the
      vaccines. RESULTS: Vaccine protection from infection was demonstrated in 10 out
      of 12 macaques immunized with recombinant gp120. Complete protection from
      infection was achieved with all of the animals that received the SBAS2-W6.1D
      formulation, a potent inducer of both T-cell and humoral immune responses.
      Partial protection was achieved with SBAS1-W6.1D, a formulation based on
      immunomodulators known to induce T-cell responses in humans. In vaccinated
      animals that were infected, virus load was reduced and infection was delayed.
      CONCLUSIONS: In a relatively large number of primates, vaccine efficacy was
      demonstrated with a clinically relevant HIV-1 vaccine. These results reveal that
      it is possible to induce sterilizing immunity sufficient to protect from
      infection with SHIV which was passaged multiple times in vivo. Our findings have
      implications for current HIV-1 clinical vaccine trials and ongoing efforts to
      develop safe prophylactic AIDS vaccines.

PMID- 9543434
TI  - The duration of viral suppression during protease inhibitor therapy for HIV-1
      infection is predicted by plasma HIV-1 RNA at the nadir.
AB  - OBJECTIVE: To determine markers that are associated with the durability of
      virologic response to therapy with HIV protease inhibitors in HIV-infected
      individuals. DESIGN: This study encompassed two retrospective analyses of the
      duration of virologic response to protease inhibitor therapy. The first analysis
      included 29 patients receiving either monotherapy or combination therapy with the
      protease inhibitor ritonavir whose plasma HIV RNA levels rebounded from the point
      of greatest decline with mutations associated with resistance to ritonavir. The
      second analysis included a cohort of 102 patients who initially responded to
      randomized treatment with either monotherapy with ritonavir or combination
      therapy with ritonavir and zidovudine. METHODS: Durability of response was
      defined as the time from the initiation of therapy to the point at which plasma
      HIV RNA displayed a sustained increase of at least 0.6 log10 copies/ml from the
      nadir value. In the first analysis, durability of response was analyzed with
      respect to baseline HIV RNA, HIV RNA at the nadir, and the drop in HIV RNA from
      baseline to the nadir. In the second analysis, time to rebound was examined using
      Kaplan-Meier analysis, stratifying by either baseline HIV RNA or HIV RNA at the
      nadir. RESULTS: In both analyses, the durability of response was not highly
      associated with either baseline RNA or the magnitude of RNA decline from
      baseline. Instead, a strong relationship was observed between the durability of
      response and the nadir plasma HIV-1 RNA value (P < 0.01). The nadir in viral load
      was generally reached after 12 weeks of randomized therapy. CONCLUSIONS: Viral
      RNA determinations at intermediate timepoints may be prognostic of impending
      virologic failure of protease inhibitor therapy. Therapeutic strategies that
      allow intensification of initial antiretroviral regimens in the subset of
      patients with incomplete virological response before the emergence of high level
      resistance should be investigated.

PMID- 9543436
TI  - The effects of lamivudine treatment on HIV-1 disease progression are highly
      correlated with plasma HIV-1 RNA and CD4 cell count.
AB  - OBJECTIVE: To determine the value of plasma HIV-1 RNA and CD4 cell count as
      predictors of the clinical benefit of antiretroviral treatment. DESIGN AND
      SETTING: The CAESAR (Canada, Australia, Europe, South Africa) trial randomized
      1840 patients [inclusion CD4 cell count, 25-250 x 10(6)/l] to add either placebo,
      lamivudine (3TC) or 3TC plus loviride in a double-blinded fashion to baseline
      treatments (zidovudine, zidovudine-didanosine or zidovudine-zalcitabine) for 1
      year. PATIENTS: This analysis included 487 patients with data on CD4 cell count
      and HIV-1 RNA after 12-20 weeks of treatment and subsequent follow-up for
      clinical progression. MAIN OUTCOME MEASURES: The correlation between 12-20-week
      change in CD4 cell count, HIV-1 RNA and progression to AIDS or death in the
      placebo group was used to predict the clinical benefit of the 3TC-containing arms
      of the trial, given their effects on CD4 cell count and HIV-1 RNA. RESULTS: After
      12-20 weeks of treatment, HIV-1 RNA fell by 0.37 log10 copies/ml in the 3TC arms
      versus a rise of 0.05 log10 copies/ml in the placebo arm. The 12-20-week CD4 cell
      count rose by 35 x 10(6)/l in the 3TC arm versus a fall of 8 x 10(6)/l in the
      placebo arm. After 12-20 weeks of treatment, a reduction in HIV-1 RNA of 1 log10
      at 12-20 weeks predicted a 49% reduction in progression [hazard ratio (HR), 0.51;
      95% confidence interval (CI), 0.30-0.87] and a rise in CD4 cell count of 50 x
      10(6)/l predicted a 51% reduction in progression (HR, 0.49; 95% CI, 0.33-0.73).
      Using the model from the placebo arm, the rises in CD4 cell count and reductions
      in HIV-1 RNA during 3TC treatment predicted a 59% reduction in progression to
      AIDS or death. The observed clinical benefit was a 57% reduction in progression
      for the 3TC arms versus placebo (HR, 0.43; 95% CI, 0.26-0.71). CONCLUSIONS: Rises
      in CD4 cell count and reductions in HIV-1 RNA were reliable in predicting the
      clinical benefit of 3TC in the CAESAR trial.

PMID- 9543437
TI  - Decreasing incidence of HIV and sexually transmitted diseases in young Thai men:
      evidence for success of the HIV/AIDS control and prevention program.
AB  - OBJECTIVE: To determine whether HIV and sexually transmitted disease (STD)
      incidence rates among young men in northern Thailand have declined since the
      establishment of the '100% Condom Program', and to prospectively document changes
      in the association between behavioral risk factors and incident HIV and STD
      infections. SETTING: Thirteen military bases in northern Thailand. METHODS:
      Serial prospective cohorts of 19-23-year-old male conscripts (n = 4086) inducted
      into military service from six northern Thai provinces between 1991 and 1993 were
      followed at 6-month intervals for incident HIV and STD through May 1995. HIV
      incidence was determined by serology, and incident STD were reported by
      conscripts as diagnosed by health-care providers. RESULTS: HIV incidence declined
      from a rate of 2.48 per 100 person-years during 1991-1993 to 0.55 per 100 person
      years during 1993-1995. STD incidence showed an even greater decline, with a 10
      fold decrease from 1991-1993 to 1993-1995. Behavioral risk factors for incident
      STD infections included a history of prior STD and sex with girlfriends and sex
      workers. Inconsistent condom use remained a strong predictor of incident STD
      among brothel visitors. Other previously-reported risk factors in 1991-1993 such
      as illicit drug use, frequency and cost of brothel visits, and low socioeconomic
      status were not associated with incident STD or HIV in 1993-1995. CONCLUSIONS:
      Although several studies have recently reported decreased prevalence of HIV and
      STD infections in Thailand, these data demonstrate that a dramatic decrease in
      the incidence rates of STD, including HIV infection, has occurred among young men
      in military service in northern Thailand. The Thai AIDS prevention and control
      program might be implemented by other countries experiencing major epidemics of
      heterosexually transmitted HIV infections. Similar prevention programs targeted
      at other populations in Thailand and elsewhere in Asia are needed to decrease the
      spread of the HIV epidemic.

PMID- 9543442
TI  - Resistance and cross-resistance with saquinavir and other HIV protease
      inhibitors: theory and practice.

PMID- 9543443
TI  - The frequency of resistant mutant virus before antiviral therapy.
AB  - OBJECTIVE: To calculate the expected prevalence of resistant HIV mutants before
      antiviral therapy. DESIGN: HIV replication generates virus mutants. The
      prevalence of these mutants is determined by mutation and selection/fitness. Some
      mutations will confer drug resistance and it is crucial for the success of
      antiviral drug therapy to determine whether these resistant viruses are present
      before the initiation of therapy. METHODS: A quasispecies equation was used to
      calculate the expected frequency of drug-resistant virus prior to therapy.
      RESULTS AND CONCLUSIONS: We show how the pretreatment frequency of resistant
      virus depends on the number of point mutations between wild-type and mutant
      virus, the selective disadvantage of the resistant mutant and the intermediate
      mutants, and the mutation rate.

PMID- 9543444
TI  - Infection of primary dermal microvascular endothelial cells by Kaposi's sarcoma
      associated herpesvirus.
AB  - OBJECTIVE: To develop an in vitro model for infection of primary human cells with
      Kaposi's sarcoma (KS) herpesvirus (KSHV). DESIGN: The recent identification of a
      herpesvirus associated with KS, its successful isolation in vitro, and its
      complete DNA sequencing facilitates experiments on the pathogenesis of AIDS
      related KS. Completed studies demonstrate that the endothelial cells lining the
      vascular slits in KS lesions are productively infected with KSHV and may be the
      principal site of virus replication. We have designed a model system to study the
      infection of primary human cells with KSHV. METHODS: A coculture technique was
      used with KS cells (KS-1) and primary dermal microvascular endothelial cells.
      RESULTS: We detected increasing viral DNA concentrations as well as viral mRNA
      suggesting that a productive virus infection occurs in the target cells.
      Infection of these cells is dose- and time-dependent and is inhibited by
      lobucavir, foscarnet and 9-(2-phosphomethoxyethyl) adenine. With a modification
      of the model, KSHV can be serially passaged in primary cells in excess of 16
      passages. CONCLUSIONS: This novel model assay system makes new studies on the
      role of KSHV and KSHV-induced cellular products on the pathogenesis of KS
      possible. It also provides a high volume screening method to detect agents that
      inhibit KSHV infection of primary endothelial cells.

PMID- 9543445
TI  - Phase II controlled trial of post-exposure immunization with recombinant gp160
      versus antiretroviral therapy in asymptomatic HIV-1-infected adults. VaxSyn
      Protocol Team.
AB  - OBJECTIVE: To alter the natural course of HIV-1 infection by inducing or
      potentiating immune responses to HIV-1 envelope glycoprotein. DESIGN:
      Multicentre, double-blind, three-arm, placebo-controlled study. SETTING:
      Outpatients attending clinics in two University Hospitals. PATIENTS: Ninety-nine
      asymptomatic HIV-1-infected adults with CD4+ T-cell counts > 400 and < 600 x
      10(6)/l and no previous antiretroviral therapy were included. INTERVENTIONS:
      Patients were randomly assigned to three groups treated with: (i) gp160 in alum
      over a 2-year period in combination with placebo for the full study duration (n =
      32); (ii) gp160 in alum over a 2-year period in combination with zidovudine for
      the full study duration (n = 34); and (iii) alum over a 2-year period in
      combination with zidovudine for the full study duration (n = 33). RESULTS:
      Immunotherapy was well tolerated and no significant differences in disease
      progression were seen in the treatment groups. The majority of patients (85%)
      receiving gp160 showed persistent lymphoproliferative responses to the immunogen
      and to a different Env antigen preparation. CD4+ cell count changes in patients
      receiving zidovudine alone were significantly higher than those seen in patients
      receiving immunotherapy alone after 1 year of treatment. Zidovudine
      administration was associated with initial transient reduction of plasma
      viraemia. CONCLUSIONS: Prolonged immunization with a soluble HIV-1 subunit
      provided no benefit to asymptomatic HIV-1-infected patients and was inferior to
      zidovudine monotherapy. Furthermore, immunization with gp160 shortened the
      duration of the transient viral load reduction induced by zidovudine.

PMID- 9543446
TI  - Role of transforming growth factor-beta1 in the suppressed allostimulatory
      function of AIDS patients.
AB  - BACKGROUND: The T-cell stimulatory function of accessory cells isolated from
      peripheral blood lymphocytes of AIDS patients has been reported to be suppressed.
      These patients also have elevated levels of the immunosuppressive factor
      transforming growth factor (TGF)-beta1 in their serum and plasma. OBJECTIVE: To
      explore the role of TGF-beta1 in the loss of accessory cell function of
      peripheral blood lymphocytes from AIDS patients. METHODS: Fluorescent labeled
      anti-TGF-beta1 and confocal microscopy were used to detect the presence of TGF
      beta1 on the cell membrane of dendritic cells. To assess the role of TGF-beta1 in
      the inhibition of accessory cell function in AIDS, antibodies against TGF-beta1
      or the TGF-beta1 type III receptor, beta-glycan, were added to a mixed lymphocyte
      reaction. RESULTS: TGF-beta1 was detected on the cell membrane of dendritic cells
      isolated from AIDS patients. The addition of blocking antibodies against either
      TGF-beta1 or beta-glycan restored the T-cell stimulatory function to accessory
      cells from these patients. CONCLUSIONS: T-cell stimulatory function was not
      irreversibly lost in AIDS patients. Our data suggested that beta-glycan-TGF-beta1
      immunosuppressive complexes may contribute to the suppression of accessory cell
      function in these patients.

PMID- 9543447
TI  - Pilot study of zidovudine-lamivudine combination therapy in vertically HIV
      infected antiretroviral-naive children.
AB  - OBJECTIVE: To examine tolerance and efficacy of a zidovudine plus lamivudine
      combination in HIV-infected children without previous exposure to antiretroviral
      drugs. METHODS: Thirteen vertically infected children (aged 4 months to 10 years)
      were treated with zidovudine (approximately 100 mg/m2 three times daily) and
      lamivudine (4 mg/kg twice daily). CD4 T-cell count, plasma HIV RNA concentration,
      complete blood count and blood chemistry profile were monitored before treatment
      and at months 1, 3 and 6. RESULTS: In general, treatment was well tolerated. One
      child developed slight neutropenia in the presence of antineutrophil antibodies.
      CD4 cell count increased from 851+/-621 x 10(6)/l at baseline to 1073+/-945 x
      10(6)/l at month 3 (P < 0.05) and to 1133+/-728 x 10(6)/l at month 6 (P = 0.01).
      CD4+ cell count increased in 10 patients after 3 months and in 11 patients
      treated for 6 months. One child showed a continuous decrease of CD4 cells despite
      treatment. Before treatment the plasma HIV RNA concentration was elevated in nine
      children (> 4.0 log10 copies/ml) and decreased in all of them: by month 1, the
      mean reduction was -1.16 log10 copies/ml; by month 3, -1.38 log10 copies/ml; and
      by month 6, -1.53 log10 copies/ml compared with baseline. However, one child
      showed steadily increasing viral load from 2.7 log10 copies/ml to a maximum of
      4.52 log10 copies/ml, surprisingly in association with increasing numbers of CD4
      cells. This child was switched to a new combination regimen after 6 months of
      treatment. Plasma HIV RNA levels below limit of detection were reached in six
      patients: after 1 month of treatment in one patient, after 3 months in five
      patients, and after 6 months in six patients. There was a mean reduction of viral
      load from 4.56 log10+/-4.63 log10 copies/ml (n = 13) to 3.8 log10+/-3.9 log10
      copies/ml (P < 0.05; n = 9) after 1 month, to 3.67 log10+/-3.88 log10 copies/ml
      (P < 0.01; n = 13) after 3 months, and to 3.64 log10+/-3.95 log10 copies/ml after
      6 months of treatment (P < 0.001; n = 13). CONCLUSIONS: This pilot study
      demonstrates the feasibility of zidovudine-lamivudine combination in children not
      previously exposed to antiretroviral drugs. This promising combination should
      therefore be evaluated in larger trials.

PMID- 9543448
TI  - High incidence of anal high-grade squamous intra-epithelial lesions among HIV
      positive and HIV-negative homosexual and bisexual men.
AB  - OBJECTIVE: The incidence of anal cancer among homosexual men exceeds that of
      cervical cancer in women, and HIV-positive homosexual men may be at even higher
      risk than HIV-negative men. Cervical cancer is preceded by high-grade squamous
      intra-epithelial lesions (HSIL) and anal HSIL may similarly be the precursor to
      anal cancer. In this study, we describe the incidence of and risk factors for
      HSIL in HIV-positive and HIV-negative homosexual and bisexual men. DESIGN:
      Prospective cohort study of HIV-positive and HIV-negative homosexual men.
      SETTING: The University of California, San Francisco. PATIENTS: 346 HIV-positive
      and 262 HIV-negative men enrolled at baseline, 277 HIV-positive and 221 HIV
      negative homosexual men followed after baseline. STUDY DESIGN: A questionnaire
      was administered detailing lifestyle habits, medical history and sexual
      practices. Anal swabs for cytology and human papillomavirus studies were
      obtained, followed by biopsies of visible lesions. Human papillomavirus testing
      was performed using polymerase chain reaction (PCR) and 'hybrid capture'. Blood
      was obtained for HIV testing and measurement of CD4 levels. MAIN OUTCOME
      MEASURES: Incident HSIL. RESULTS: HIV-positive men were more likely to develop
      HSIL than HIV-negative men relative risk (RR), 3.7; 95% confidence interval (CI),
      2.6-5.7. Life-table estimates of the 4-year incidence of HSIL was 49% (95% CI, 41
      56) among HIV-positive men and 17% (95% CI, 12-23) among HIV-negative men. Among
      HIV-positive men, those with lower baseline CD4 counts (P = 0.007) and persistent
      infection with one or more human papillomavirus types, determined using PCR (P =
      0.0001), were more likely to develop HSIL. CONCLUSIONS: HIV infection, lower CD4
      levels and human papillomavirus infection were associated with high rates of
      incident HSIL among homosexual men. However, high rates were found at all CD4
      levels among HIV-positive men and among HIV-negative men.

PMID- 9543450
TI  - Breastfeeding, genetic, obstetric and other risk factors associated with mother
      to-child transmission of HIV-1 in Sao Paulo State, Brazil. Sao Paulo
      Collaborative Study for Vertical Transmission of HIV-1.
AB  - OBJECTIVES: To evaluate the effect of maternal, obstetric, neonatal and post
      natal factors on the risk of vertical transmission of HIV-1. DESIGN: Multicentre
      retrospective cohort study. SETTING: Obstetric and paediatric clinics in four
      cities in Sao Paulo State, Brazil. MAIN OUTCOME: Child's HIV-1 infection status.
      METHODS: Data were collected by standardized record abstraction and interview on
      553 children born to women identified as HIV-1-infected before or at delivery.
      Paediatric infection was determined by immunoglobulin G anti-HIV-1 tests at age
      18 months or by AIDS diagnosis at any age. Multivariate logistic regression was
      used to assess the effect of potential risk factors on vertical transmission of
      HIV-1. RESULTS: HIV-1 infection status was determined for 434 children (follow-up
      rate of 78%); 69 were classified as HIV-1-infected [transmission risk, 16%; 95%
      confidence interval (CI), 13-20%]. In multivariate analysis, advanced maternal
      HIV-1 disease [odds ratio (OR), 4.5; 95% CI, 2.1-9.5], ever breastfed (OR, 2.2;
      95% CI, 1.2-4.2), child's negative Rhesus blood group (OR, 2.5; 95% CI, 1.2-5.5),
      third trimester amniocentesis (OR, 4.1; 95% CI, 1.2-13.5) and black racial group
      (OR, 0.3; 95% CI, 0.1-0.9) were independently and significantly associated with
      mother-to-child transmission of HIV-1. Transmission was increased marginally with
      prematurity, more than 10 lifetime sexual partners and prolonged duration of
      membrane rupture. No association was found between child's HIV-1 infection and
      mode of delivery or serological evidence of syphilis during pregnancy.
      CONCLUSION: These findings support the importance of severity of maternal HIV-1
      disease in the risk of vertical transmission of HIV-1, indicate measures to
      reduce transmission by avoiding amniocentesis and breastfeeding and suggest that
      race and Rhesus blood type may be markers for genetic susceptibility to
      infection.

PMID- 9543449
TI  - The Cote d'Ivoire national HIV counseling and testing program for tuberculosis
      patients: implementation and analysis of epidemiologic data.
AB  - OBJECTIVES: To describe the implementation of a free, voluntary and confidential
      HIV counseling and testing program for patients with newly diagnosed tuberculosis
      at the eight large outpatient tuberculosis centers in Cote d'Ivoire, and to
      present epidemiologic findings on participating patients. DESIGN: HIV counseling
      and testing program with ongoing HIV serosurveillance. METHODS: HIV counseling
      and testing services were established at the two tuberculosis centers in Abidjan
      in 1989 and were extended to six centers in the Cote d'Ivoire interior in the
      first half of 1994. Characteristics of counseled patients, acceptance rates of
      HIV testing, and HIV serologic results were analyzed for all eight centers from
      1994 to 1996. Temporal trends in HIV seropositivity rates were examined for the
      two centers of Abidjan from 1989 to 1996. RESULTS: From July 1994 through
      December 1996, 17 946 (91.8%) out of 19 594 patients who were counseled at the
      eight centers in Cote d'Ivoire consented to HIV testing, of whom 7749 (43.2%)
      were HIV-seropositive. The highest rates of 47.0 and 45.6% were found in the two
      centers in Abidjan, with rates ranging from 32.9 to 42.4% in the six centers in
      the interior. HIV-seropositive tuberculosis patients from each of the 50
      districts in Cote d'Ivoire were identified. In Abidjan, the HIV seropositivity
      rate remained relatively stable among men (46.7% in 1989, 48.5% in 1991, 43.6% in
      1996), but rose sharply among women from 32.7% in 1989 to 50.1% in 1996.
      CONCLUSIONS: The high HIV seropositivity rates among tuberculosis patients in all
      geographic regions of Cote d'Ivoire indicate that the HIV epidemic has now spread
      throughout the country. However, the successful implementation of an extensive
      HIV counseling and testing program for more than 37000 tuberculosis patients to
      date demonstrates the commitment of the Cote d'Ivoire Ministry of Health to
      integrating HIV/AIDS prevention activities with tuberculosis control efforts.
      When logistically and economically feasible, the extension of HIV-related social
      and clinical services to HIV-seropositive tuberculosis patients should be
      considered by other national tuberculosis control programs in Africa.

PMID- 9543451
TI  - A molecular epidemiologic survey of HIV in Uganda. HIV Variant Working Group.
AB  - OBJECTIVE: Previous data, based on a small sampling of convenience, reported
      subtypes A, B, C, D, and G in Uganda, but neither the extent nor the proportion
      of these subtypes could be evaluated. To establish correctly the prevalence and
      distribution of HIV-1 subtypes, we analysed viral clades in 739 HIV-1
      seropositive specimens from different areas of Uganda. METHODS: Blood specimens
      from 1100 patients were collected in five districts of Uganda. Within this
      collection, 929 HIV-1-seroreactive samples underwent analysis of viral DNA, and
      739 were selected for further subtyping in env or pol regions. RESULTS: Using a
      combination of subtype A- and D-specific probes to C2-V3 region and DNA
      sequencing, HIV-1 env subtypes were determined in 594 specimens: 341 were of
      subtype A (57.4%), 250 of subtype D (42.1%), and three of subtype C (0.5%). Sixty
      two samples showed reactivity with both probes, suggesting potential mixed
      infections, cross-reactivity to probes, or possibly other subtypes. Subsequent
      sequence analysis of 19 randomly selected specimens revealed subtypes A (n = 4),
      D (n = 12), and C (n = 3). Sequence analysis of the 27 samples chosen from the
      remaining 83 samples, which could be amplified only with viral gp41 or protease
      gene primers, classified them as subtypes A (n = 13) and D (n = 14). No
      significant clinical, demographic, or geographic differences were found between
      HIV-1 infections with viruses of subtypes A and D, despite considerable genetic
      diversity within these clades. CONCLUSIONS: This is the first major population
      based study of the prevalent HIV-1 strains in an African country selected for
      vaccine trials. The subtyping methods we describe should be of use to
      investigators seeking to conduct large-scale screening for HIV variants in other
      populations.

PMID- 9543452
TI  - The impact of new antiretroviral regimes on HIV-associated hospital admissions
      and deaths.

PMID- 9543453
TI  - High prevalence of hepatitis G virus RNA and antibody to probable viral envelope
      protein but not both in AIDS patients' plasma.

PMID- 9543454
TI  - Fatal acute haemolysis in an AIDS patient treated with indinavir.

PMID- 9543455
TI  - New treatments for progressive multifocal leukoencephalopathy in HIV-1-infected
      patients.

PMID- 9543456
TI  - Longitudinal comparison of HIV-1 RNA burden in plasma and cerebrospinal fluid in
      two patients starting triple combination antiretroviral therapy.

PMID- 9543457
TI  - Therapeutic concentrations of indinavir in cerebrospinal fluid of HIV-1-infected
      patients.

PMID- 9543458
TI  - Resolution of azole-resistant oropharyngeal candidiasis after initiation of
      potent combination antiretroviral therapy.

PMID- 9543459
TI  - Seroprevalence of human herpesvirus-8 in healthy subjects and patients with AIDS
      associated and classical Kaposi's sarcoma in France.

PMID- 9543460
TI  - The first Zambian population-based HIV survey: saliva-based testing is accurate
      and acceptable.

PMID- 9543461
TI  - High seroprevalence of human herpesvirus-8 in pregnant women and prostitutes from
      Cameroon.

PMID- 9543462
TI  - New advances in the treatment of Alzheimer's disease. Proceedings of a symposium.
      Dallas, Texas, USA. July 12, 1997.

PMID- 9543463
TI  - A multidisciplinary team approach to managing Alzheimer's disease.
AB  - Patients with Alzheimer's disease experience a range of symptoms that may
      overwhelm the patients, their families, and the people responsible for their
      care. With today's drive to reduce health care costs, any plan for managing these
      patients must produce maximum effectiveness at the lowest possible cost. A
      multidisciplinary team potentially offers both effective and efficient dementia
      care by eliminating duplicative or ineffective services and maintaining the
      optimum health of the patient and family.

PMID- 9543464
TI  - Metrifonate: overview of safety and efficacy.
AB  - Metrifonate is a cholinesterase inhibitor with a long-lasting inhibition that
      raises brain acetylcholine levels. It is well-absorbed and has limited binding to
      serum proteins. In preliminary studies of its utility in the treatment of
      Alzheimer disease's (AD), it led to improvements of cognition or reduced the rate
      of decline of cognition compared with placebo. It also benefited the global
      function of these patients. Side effects include nausea, cramping, and diarrhea.
      Metrifonate has promise as a well-tolerated treatment of the symptoms of AD.

PMID- 9543465
TI  - Pharmacokinetics and drug interactions of cholinesterase inhibitors administered
      in Alzheimer's disease.
AB  - Cholinesterase inhibitors are the first agents to be successfully developed
      specifically for the treatment of cognitive decline associated with Alzheimer's
      disease. Basic knowledge of their pharmacokinetics is important to their
      appropriate administration. Their pharmacokinetics help determine the magnitude
      and duration of their pharmacologic effects, and also the manner in which they
      affect the degree of cholinesterase inhibition and recovery. The clinical utility
      of measuring these values in daily practice awaits further research. Drug
      interactions with cholinesterase inhibitors may occur by pharmacokinetic or
      pharmacodynamic mechanisms. For the most part, interactions that are mediated by
      the hepatic cytochrome P-450 system have been inadequately evaluated.

PMID- 9543466
TI  - Preclinical pharmacology of metrifonate.
AB  - Alzheimer's disease is a chronic neurodegenerative disorder that is characterized
      by memory impairment, cognitive dysfunction, behavioral disturbances, and
      deficits in activities of daily living. A consistent observation in these
      patients is that cholinergic neurons are affected and deteriorate over time,
      leading to decreased levels of acetylcholine (ACh). Acetylcholinesterase (AChE)
      inhibitors, which attempt to prevent the breakdown of ACh, may be classified as
      short acting, intermediate acting, and long acting based on AChE regeneration
      time. Metrifonate is converted by a nonenzymatic process to the long-acting
      cholinesterase inhibitor 2,2-dichlorovinyl dimethyl phosphate (DDVP).
      Acetylcholinesterase inhibition produced by metrifonate occurs rapidly, is dose
      dependent, can be detected by inhibition measured in red blood cells, and can be
      reversed by oxime administration. Metrifonate and DDVP improved performance in
      young rats; cognitive improvement in aged rats also was observed. Both agents
      were well tolerated and did not have significant effects on various preclinical
      pharmacologic safety tests.

PMID- 9543468
TI  - Prospects of developing interventions to prevent Alzheimer's disease.
AB  - Based largely on recommendations of scientists from around the world, it is
      possible to discover treatments designed to maintain independent functioning of
      patients with Alzheimer's disease. It is hoped that discussion of critical
      targets for intervention, and possible strategies for altering the degenerative
      course of the disease will spur interested groups into action.

PMID- 9543467
TI  - Economic considerations in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the third most expensive disease in the United
      States, costing society approximately $100 billion each year. It is one of the
      most prevalent illnesses in the elderly population, and with the aging of
      society, will become even more significant. Costs associated with AD include
      direct medical costs such as nursing home care, direct nonmedical costs such as
      in-home day care, and indirect costs such as lost patient and caregiver
      productivity. Medical treatment may have economic benefits by slowing the rate of
      cognitive decline, delaying institutionalization, reducing caregiver hours, and
      improving quality of life. Pharmacoeconomic evaluations have shown positive
      results regarding the effect of drug therapy on nursing home placement,
      cognition, and caregiver time.

PMID- 9543470
TI  - Epidemiology of mild pneumonia.
AB  - Clinicians define mild pneumonia as patients who are "not too sick," have normal
      respiratory and mental status, and are able to maintain oral intake. As yet there
      is no uniform definition of mild pneumonia. By inference, mild pneumonia occurs
      in younger patients with less comorbidity and has a better outcome than pneumonia
      that is moderate to severe. "Atypical" pathogens such as Mycoplasma pneumoniae,
      Chlamydia pneumoniae and respiratory tract viruses are common causes of mild
      pneumonia.

PMID- 9543471
TI  - Management of pneumonia in the outpatient setting.
AB  - Most patients with pneumonia never reach the hospital but are managed in the
      community. Unlike patients admitted to the hospital, in most, no investigations
      are performed and the diagnosis is based on clinical features. Less than half of
      those with clinical pneumonia have radiographic infiltrates and some of those
      with lower respiratory tract infection that is not considered to be pneumonia do.
      Few studies have investigated this condition, partly because of these diagnostic
      difficulties. The importance of distinction of these conditions is uncertain at
      present. The role of microbiological investigations in patients with pneumonia in
      the community requires clarification. For most patients it is unlikely that such
      tests will alter management, but it is not possible to predict those in whom such
      tests may help. What little is known about the microbial cause of pneumonia
      managed outside of the hospital is that the causative pathogens are similar to
      those found in studies of hospitalized patients, with the exception of pathogens
      usually associated with severe illness such as legionella and staphylococci,
      which are uncommon. Empirical antibiotic therapy can be predicted from the above
      findings, but much further research is required to fill in current gaps in our
      knowledge.

PMID- 9543472
TI  - Impact of influenza and other community-acquired viruses.
AB  - The incidence of community-acquired pneumonia peaks during the winter season each
      year. Increases in mortality from these pneumonias and influenza-like illnesses
      (P&I) above an "epidemic threshold" for 2 or more weeks generally signify
      increased numbers of influenza virus infections in the community, although peaks
      in P&I mortality typically lag a few weeks behind peaks in influenza virus
      activity. Most of the pneumonias cases found during influenza virus epidemics are
      due to secondary bacterial infections, with an increase in the frequency of
      Staphylococcus aureus over that seen in nonepidemic periods. One interaction
      between bacteria and influenza viruses that may increase disease severity by
      increasing growth of the virus is proteolytic cleaving of the hemagglutinin
      mediated directly or indirectly by bacterial products. Influenza virus infections
      also have many effects on the host that can enhance secondary bacterial
      infections; included are impairments of mucus clearance and T cell,
      polymorphonuclear cell and macrophage functions, as well as alterations in
      respiratory epithelium that can enhance adherence of bacteria. Recent studies
      indicate that the role of respiratory syncytial virus infections in causing acute
      pulmonary syndromes in elderly individuals, including secondary bacterial
      pneumonia, is essentially equivalent to that of influenza A viruses during years
      when there is not a severe influenza epidemic. Although other respiratory viruses
      can occasionally cause or facilitate the development of community-acquired
      pneumonia, currently available epidemiological data do not support significant
      roles for them relative to those of influenza and respiratory syncytial viruses.

PMID- 9543473
TI  - What new antibiotics to offer in the outpatient setting.
AB  - The treatment of community-acquired pneumonia is empiric. Guidelines have been
      developed to assist the clinician in selecting antibiotics to cover the likely
      pathogens. Given the difficulty of predicting an etiologic agent from patient
      characteristics, radiologic findings, and laboratory studies, initial regimens
      recommend broad-spectrum coverage. In some circumstances, two antibiotics may be
      required. The prevalence of resistant organisms is increasing and must be
      considered when prescribing treatment. Patient compliance is essential for
      successful therapy but diminishes with inconvenient dosing schedules and with
      poorly tolerated medicines. A number of novel antimicrobials have either been
      just launched or are in the late stages of development. Most have been developed
      in an attempt to address the above concerns. This article focuses on the new oral
      cephalosporins, macrolides, and fluoroquinolones, and discusses the place of each
      in the therapy of community-acquired pneumonia.

PMID- 9543474
TI  - Duration and route of antibiotic therapy in community-acquired pneumonia: switch
      and step-down therapy.
AB  - The treatment of hospitalized patients with community-acquired pneumonia (CAP)
      has traditional been with intravenous antibiotics. More recently, the focus of
      this antibiotic therapy has been empiric and based on the most likely pathogens
      in a given patient. The concept of when and how to approach the patient for
      conversion to oral therapy, known as switch therapy, is now the focus of
      controversy. Recently, several studies have emerged from the literature that shed
      some light on the subject of switch therapy for CAP. Although the data are
      limited at this time, it seems clear that switching to oral antibiotics in
      selected low-risk patients may be feasible and safe. In this article, we focus on
      the problem and help formulate a practical approach to switching patients from
      intravenous antibiotics to oral therapy for CAP.

PMID- 9543475
TI  - Emergence of antimicrobial resistance in community-acquired pulmonary pathogens.
AB  - Antibiotic resistance to the common respiratory tract pathogens is increasing
      worldwide. Penicillin-resistant pneumococci are of particular concern. Most
      strains of penicillin-resistant Streptococcus pneumoniae have intermediate
      resistance to penicillin, and highly resistant strains are rare at present.
      Careful selection of antibiotics with low resistance potential and excellent
      activity against highly penicillin-resistant pneumococci (ie, cefotaxime,
      ceftriaxone, cefepime, cefprozil, doxycycline, levofloxacin, sparfloxacin, and
      meropenem) is the best current strategy to delay or increase the emergence of
      highly penicillin-resistant strains of S pneumoniae.

PMID- 9543476
TI  - Chronic pneumonias.
AB  - Some patients present in the outpatient setting with persistent respiratory and
      constitutional symptoms in association with unresolving parenchymal infiltrates
      on the chest radiograph. Clinicians must entertain a wide differential diagnosis
      as many infectious and noninfectious conditions can lead to this chronic
      pneumonia syndrome. The clinical presentation and radiographic abnormalities are
      often nonspecific. A significant proportion of patients have no underlying
      predisposing illness, and most of the bacterial pathogens are often considered
      constituents of the "normal respiratory flora." Accurate diagnosis generally
      requires bronchoscopic evaluation. Prolonged therapy is essential. This article
      reviews the epidemiology and the predominant bacterial, mycobacterial, and fungal
      pathogens associated with this syndrome. A brief discussion of some of the
      noninfectious processes is also included.

PMID- 9543478
TI  - Radiographic findings in Klebsiella (Friedlander's) pneumonia: the bulging
      fissure sign.

PMID- 9543477
TI  - Strategies for prevention of community-acquired pneumonia.
AB  - Our rapidly expanding knowledge of the cause and pathogenesis of Community
      acquired pneumonia (CAP) offers new opportunities to prevent this disease.
      Influenza vaccine is effective for the prevention of respiratory illness,
      including pneumonia, in the setting of influenza A and B infection. Pneumococcal
      vaccine is effective for preventing the most common form of bacterial CAP, but it
      is most effective when administered early in the course of chronic illnesses.
      Even with the widespread availability and proven efficacy of influenza and
      pneumococcal vaccines, their use has remained suboptimal. Rimantadine and
      Amantadine have also been used successfully for prevention of influenza A
      infection. Further improvement in strategies for the prevention of CAP lies in
      the development of new and improved vaccines, enhanced environmental control, and
      general education of physicians and the public, so that new approaches such as
      hospital-based immunization can be applied.

PMID- 9543479
TI  - Neocortical efferent neurons with very slowly conducting axons: strategies for
      reliable antidromic identification.
AB  - Although simple in concept, reliable antidromic identification of efferent
      populations poses numerous technical challenges and is subject to a host of
      sampling biases, most of which select against the detection of the neurons with
      slowly conducting axons. This problem is particularly acute in studies of the
      neocortex. Many neocortical efferent systems have large sub-populations with very
      slowly conducting, nonmyelinated axons and these elements have been relatively
      neglected in antidromic studies of neocortical neurons. The present review
      attempts to redress this problem by analyzing the steps that must necessarily
      precede antidromic identification and the sampling biases associated with each of
      these steps. These steps include (1) initial recognition that the microelectrode
      is near a neuron; (2) activation of the efferent axon via the stimulating
      electrode; (3) conduction of the antidromic impulse from stimulation site to
      soma; (4) detection of the antidromic spike in the extracellular record and (5)
      discriminating antidromic from synaptic activation. Experimental strategies are
      suggested for minimizing the sampling biases associated with each of these steps;
      most of which can be reduced or eliminated by appropriate experimental
      procedures. Careful attention to such procedures will make it possible to better
      understand the nature and function of the information flow along the very slowly
      conducting axonal systems of the neocortex.

PMID- 9543480
TI  - Multiple fragment statistical analysis of post-spike effects in spike-triggered
      averages of rectified EMG.
AB  - Spike-triggered averaging of EMG is a useful experimental technique for revealing
      functional connectivity from central neurons to motoneurons. Because EMG
      waveforms constitute time series, statistical analysis of spike-triggered
      averages is complicated. Empirical methods generally have been employed to detect
      the presence of post-spike effects (PSEs), since, as we argue in this report, it
      is not feasible to develop a rigorous yet sensitive statistical test that detects
      PSEs in a single grand average of rectified EMG. We have developed a method of
      multiple fragment statistical analysis (MFSA) of PSEs, based on dividing an
      experimental record into a large numbers of non-overlapping fragments. The
      calculations necessary to obtain accurate P-values using the multiple fragment
      method are simple and efficient, and therefore preliminary results can be
      obtained while recording. In this report, we present the rationale for MFSA, and
      give examples of its application. We found MFSA to have considerable utility in
      accurately testing the significance of small PSEs, and in detecting PSEs in
      shorter recordings. Statistical corrections that should be used when recording
      multiple channels simultaneously are discussed. MFSA could be implemented for
      statistical analysis of other waveforms averaged, such as evoked potentials,
      movement-related cortical potentials, or event-related desychronizations.

PMID- 9543481
TI  - [3H]-noradrenaline secretion from rat cortex synaptosomes perforated with
      Staphylococcus aureus alpha-toxin.
AB  - Rat cortex synaptosomes have been successfully perforated with high
      concentrations (> or = 400 U/ml) of Staphylococcus aureus alpha-toxin. The free
      Ca2+-concentration dependence of [3H]-noradrenaline release was similar to that
      observed for PC 12 and chromaffin cells. Release from the alpha-toxin perforated
      synaptosomes was not significantly inhibited by omega-conotoxin GVIA. Initially,
      Ca2+-dependent release was independent of MgATP (for 0.5 min), but became
      increasingly dependent on MgATP with time. Lactate dehydrogenase efflux from
      alpha-toxin-perforated synaptosomes was not different than efflux from control
      synaptosomes, and an antibody to N-ethylmaleimide-sensitive fusion protein did
      not enter the synaptosomes. [3H]-noradrenaline release was temperature and alpha
      toxin-concentration dependent. Ca2-dependent release was more resistant to
      rundown from alpha-toxin- than from streptolysin-O-perforated synaptosomes. This
      preparation of perforated synaptosomes should be useful for studies of regulated
      exocytosis from nerve endings.

PMID- 9543483
TI  - Principal component analysis of minimal excitatory postsynaptic potentials.
AB  - 'Minimal' excitatory postsynaptic potentials (EPSPs) are often recorded from
      central neurones, specifically for quantal analysis. However the EPSPs may emerge
      from activation of several fibres or transmission sites so that formal quantal
      analysis may give false results. Here we extended application of the principal
      component analysis (PCA) to minimal EPSPs. We tested a PCA algorithm and a new
      graphical 'alignment' procedure against both simulated data and hippocampal
      EPSPs. Minimal EPSPs were recorded before and up to 3.5 h following induction of
      long-term potentiation (LTP) in CA1 neurones. In 29 out of 45 EPSPs, two (N=22)
      or three (N=7) components were detected which differed in latencies, rise time
      (Trise) or both. The detected differences ranged from 0.6 to 7.8 ms for the
      latency and from 1.6-9 ms for Trise. Different components behaved differently
      following LTP induction. Cases were found when one component was potentiated
      immediately after tetanus whereas the other with a delay of 15-60 min. The
      immediately potentiated component could decline in 1-2 h so that the two
      components contributed differently into early (< 1 h) LTP1 and later (1-4 h) LTP2
      phases. The noise deconvolution techniques was applied to both conventional EPSP
      amplitudes and scores of separate components. Cases are illustrated when quantal
      size (upsilon) estimated from the EPSP amplitudes increased whereas upsilon
      estimated from the component scores was stable during LTP1. Analysis of component
      scores could show apparent double-fold increases in upsilon which are interpreted
      as reflections of synchronized quantal releases. In general, the results
      demonstrate PCA applicability to separate EPSPs into different components and its
      usefulness for precise analysis of synaptic transmission.

PMID- 9543482
TI  - A method for long term culture of murine type 2 astrocytes.
AB  - Producing cultures of mouse type 2 astrocytes is difficult as these cells have
      low proliferative ability when isolated as pure cultures. Often standard glial
      culture techniques yield mixed glial cultures from mouse which contain little or
      no type 2 glia. This has made studies of the nature and activity of type 2
      astrocytes difficult. A co-culture technique has been established to allow long
      term culturing of type 2 astrocytes which can be grown in large number and
      isolated at very high purity. This technique uses co-culture of isolated type 2
      astrocytes and their progenitor cells with microglia. Using this method, type 2
      astrocytes can be grown to high density cultures and maintained in culture for
      over a year without noticeable change in basic phenotypic characteristics. Aged
      type 2 astrocytes show increased activity of anti-oxidant enzymes suggesting that
      these cells have increased resistance to oxidative stress. This method may allow
      analysis of the development of type 2 astrocytes from progenitor cells and may
      help to identify the in vivo equivalent of these cells.

PMID- 9543484
TI  - Review of neural network applications in sleep research.
AB  - To find a better automated sleep-wake staging system for human analyses of
      numerous polygraphic records is an interesting challenge in sleep research. Over
      the last few decades, many automated systems have been developed but none are
      universally applicable. Improvements in computer technology coupled with
      artificial neural networks based systems (connectionist models) are responsible
      for new data processing approaches. Despite extensive use of connectionist models
      in biological data processing, in the past, the field of sleep research appeared
      to have neglected this approach. Only a few sleep-wake staging systems based on
      neural network technology have been developed. This paper reviews the current use
      of artificial neural networks in sleep research. Following a brief presentation
      of neural network technology, each of the existing system is described and
      attention drawn to the heterogeneity of the different processing approaches in
      sleep research. The high performances observed with systems based on neural
      networks highlight the need to integrate these tools into the field of sleep
      research.

PMID- 9543485
TI  - A technique for in vivo vascular perfusion fixation of the sheep central nervous
      system.
AB  - A method for perfusion fixation of the sheep central nervous system is described.
      The technique utilises the vascular anatomy of the spinal cord and brain to
      provide fixation that is comparable to transcardiac perfusion of the small
      animal. It can be applied with relative ease, cost effectiveness and without
      risking premature death of the animal due to complications of a major procedure
      such as thoracotomy.

PMID- 9543486
TI  - Measurements of (Na+,K+)ATPase after in vitro hypoxia and reoxygenation are
      affected by methods of membrane preparation.
AB  - (Na+,K+ )ATPase activity was evaluated in membranes from rat hippocampal slices
      after in vitro hypoxia and reoxygenation. Membranes were prepared with two
      different methods, one using an isotonic medium and another using a hypotonic
      one. The changes that were found after hypoxia went into opposite directions in
      the two cases. Membranes prepared in a hypotonic medium are probably more
      suitable for these measurements. Using these membranes, hypoxia results in a
      slight decrease of (Na+,K+)ATPase activity and in a further decrease after
      reoxygenation. We also found that expressing (Na+,K+)ATPase activity as a percent
      of total ATPase activity is appropriate for membranes prepared under hypotonic
      conditions and can unveil (by reducing variability between experiments)
      significant changes that may be masked in small samples like ours.

PMID- 9543487
TI  - Radio-iodination of neurotrophins and their delivery in vivo: advantages of
      membrane filtration and the use of disposable syringes.
AB  - This paper reports two simple improvements for the radio-iodination of
      neurotrophins and their delivery in vivo. (1) Neurotrophins can be effectively
      separated from free iodide by using membrane filtration devices. Seven methods
      for the separation of free iodide are compared, including dialysis, gel
      filtration, and membrane filtration. Membrane filtration of the iodinated protein
      has several important advantages over dialysis or gel filtration. These include
      the precise control over the final concentration; excellent recovery of the
      neurotrophin; easy and inexpensive procedure; performance of the entire procedure
      in a fume hood; and reduced volume of radioactive waste. (2) Disposable,
      inexpensive syringes are suitable for the delivery of small volumes of radio
      iodinated or non-radioactive neurotrophins. Plastic disposable insulin syringes
      are compared with Hamilton syringes. The ejection volume of the disposable
      syringes is surprisingly reliable in the dose range 2-15 microl. Their in vivo
      performance was tested by injections in the eyes of chick embryos in ovo. The
      amounts remaining in the eye varied significantly less with the disposable
      syringes. Leakage into the surrounding eye-muscles after intraocular injection
      was significantly more frequent with Hamilton syringes than with the disposable
      syringes. Thus, disposable syringes can be a reliable and cost-effective
      alternative for drug delivery of 2-15 microl volumes.

PMID- 9543488
TI  - Construction of 1 mm microdialysis probe for amino acids dialysis in rats.
AB  - We describe here a microdialysis probe with 1 mm opening for precise and confined
      dialysis area in the awake, freely moving rat. This probe is designed to allow
      the local diffusion of the perfusion medium to an area approximately 175 microm
      high, 266 microm wide (mediolateral direction), and 305 microm in rostrocaudal
      direction. In addition, the probe allows the local application of drugs to the
      same precise area of interest. The probe was constructed from a piece of 25 gauge
      tubing with 1 mm hallowed opening located 0.5 mm from the distal (inserting) end.
      The dialysis fiber which was inserted into the stainless steel 25 gauge tubing
      and cemented into place has 200 microm diameter and 5000 molecular weight cut
      off. We tested the probe diffusion extent by direct infusion of fluorogold
      through the dialysis cannula. Changes in the extracellular concentrations of
      amino acids were measured in response to infusion of veratridine a sodium channel
      activator. All amino acids tested showed a significant 80% times decrease in
      their recovery concentration when compared to their respective concentrations
      recovered through 2 mm probe constructed earlier in our laboratory (Renno et al.,
      1992). Tests in awake rats with probes in the ventrocaudal PAG showed stable
      amounts of 12 different amino acids during repeated (6-8 times) 12 min samples at
      3-5 microl/min collecting rate. Depolarization with 75 microM veratridine
      resulted in significant elevation in extracellular gamma-aminobutyric acid
      (GABA), aspartate, glutamate, taurine, glycine and citrulline. This design
      enables us to apply drugs of interest and measure the concentrations of amino
      acid neurotransmitters to a more precise, delineated and premeasured areas in the
      CNS.

PMID- 9543489
TI  - Improved method facilitates reliable APOE genotyping of genomic DNA extracted
      from formaldehyde-fixed pathology specimens.
AB  - Apolipoprotein E (APOE) genotyping of genomic DNA extracted from formaldehyde
      fixed specimens is cumbersome: there is not only a low yield or failure of PCR
      amplification (presumably due to degradation of DNA in the formaldehyde-fixed and
      paraffin-embedded tissue), but the standard method also involves the separation
      of DNA fragments as small as 48, 72, 81 and 91 bp requiring high-yield PCR
      products. Here we report about a semi-nested PCR method suitable for providing
      specific high-yield PCR products from DNA that has been extracted from
      formaldehyde-fixed specimens which initially generate low-quality templates. This
      method facilitates reliable APOE genotyping of DNA from difficult templates.

PMID- 9543490
TI  - Structure and function of plasma membrane amino acid, oligopeptide and sucrose
      transporters from higher plants.

PMID- 9543491
TI  - Halide and alkyl phenols block volume-sensitive chloride channels in human glial
      cells (U-138MG).
AB  - Swelling of cells in hypotonic media activates a volume-sensitive Cl channel with
      well-known characteristics, but its structure and its regulation are still
      largely undetermined. It also has many inhibitors and most of them are also
      blocking other types of Cl channels. The numerous inhibitors of Cl channels have
      apparently no structural relationship among them. The purpose of this study was
      to try to determine the most simple molecules that could block these channels and
      identify some common properties among inhibitors. From the 37 new molecules that
      were studied, it was found that simple halide phenols like trichloro and
      triiodophenols could block these channels in the micromolar range. Also alkyl
      phenols, like butylphenols, are very sensitive blockers, comparable to other well
      known blockers. But acidic halide phenols or nitrophenols are poor blockers. Also
      neutral polyphenols are more sensitive than acidic polyphenols. All these results
      indicate that the common basis for blocking these Cl channels is a phenol with
      hydrophobic groups, like short alkyl chains or an additional phenyl ring,
      attached to some of its sites, preferably sites 3-4-5. These results identify a
      new family of Cl channel blockers and hopefully improve our understanding of the
      blocking mechanism.

PMID- 9543492
TI  - Regulation of renal Na-HCO3 cotransporter: VIII. Mechanism Of stimulatory effect
      of respiratory acidosis.
AB  - We examined the effect of respiratory acidosis on the Na-HCO3 cotransporter
      activity in primary cultures of the proximal tubule of the rabbit exposed to 10%
      CO2 for 5 min, 2, 4, 24 and 48 hr. Cells exposed to 10% CO2 showed a significant
      increase in Na-HCO3 cotransporter activity (expressed as % of control levels, 5
      min: 142 +/- 6, 2 hr: 144 +/- 13, 4 hr: 145 +/- 11, 24 hr: 150 +/- 15, 48 hr: 162
      +/- 24). The increase in activity was reversible after 48 hr. The role of protein
      kinase C (PKC) on the stimulatory effect of respiratory acidosis on the
      cotransporter was examined in presence of PKC inhibitor calphostin C or in
      presence of PKC depletion. Both calphostin C and PKC depletion prevented the
      effect of 10% CO2 for 5 min or 4 hr to increase the activity of the
      cotransporter. 10% CO2 for 5 min or 4 hr increased total and particulate fraction
      PKC activity. To examine the role of phosphotyrosine kinase (PTK) on the increase
      in cotransporter activity we studied the effect of two different inhibitors, 2
      hydroxy-5-(2,5-dihydroxylbenzyl) aminobenzoic acid (HAC) and methyl 2,5
      dihydroxycinnamate (DHC) which inhibit phosphotyrosine kinase in basolateral
      membranes. Cells were pretreated either with vehicle or HAC or DHC and then
      exposed to 10% CO2 for 5 min or 4 hr. In cells treated with vehicle, 10% CO2
      significantly increased cotransporter activity as compared to control cells
      exposed to 5% CO2. This stimulation by 10% CO2 was completely prevented by HAC or
      DHC at 5 min (5% CO2: 1.8 +/- 0.2, 10% CO2: 2.6 +/- 0.2, 10% CO2 + HAC: 1.6 +/-
      0.2, 10% CO2: +DHC: 2.0 +/- 0.3 pH unit/min) and also at 4 hr. The protein
      synthesis inhibitors actinomycin D and cycloheximide appear to prevent the effect
      of 10% CO2 for 4 hr on the cotransporter. Our results show that early respiratory
      acidosis stimulates the Na-HCO3 cotransporter through PKC and PTK-dependent
      mechanisms and the late effect appears to be mediated through protein synthesis.

PMID- 9543493
TI  - The staphylococcal pore-forming leukotoxins open Ca2+ channels in the membrane of
      human polymorphonuclear neutrophils.
AB  - The ability of leukotoxins secreted by Staphylococcus aureus to modify the
      permeability of the membrane of human polymorphonuclear neutrophils has been
      studied by spectrofluorometry and appropriate fluorescent probes. This family of
      bicomponent leukotoxins is constituted by, at least, three pairs of proteins:
      LukS-PV/LukF-PV, HlgA/HlgB, HlgC/HlgB. After binding of both components to the
      membrane, each pair induces influxes of divalent cations and ethidium in
      polymorphonuclear neutrophils, although with different intensities. The influx of
      divalent cations appears sooner than the influx of ethidium. The pathway for
      divalent cations is not permeable to monovalent cations (Na+, K+, ethidium+) and
      is blocked by Ca2+ channel inhibitors that do not block the fluxes of ethidium
      and monovalent cations. It is concluded that the leukotoxins bind to a receptor
      linked to a divalent cation-selective channel or to the channel itself which is
      activated. Then, the leukotoxins open a second pathway by insertion into the
      membrane and subsequent formation of aspecific pores allowing an influx of
      ethidium.

PMID- 9543494
TI  - Hypothyroidism decreases the ATP sensitivity of KATP channels from rat heart.
AB  - The effects of thyroid status on the properties of ATP-sensitive potassium
      channels were investigated. Single-channel recordings were made using excised
      inside-out membrane patches from enzymatically dissociated ventricular myocytes
      from hearts of control and thyroidectomized rats and each group was studied with
      and without administration of thyroid hormone. In patches excised from
      hypothyroid myocytes the IC50 for ATP inhibition of KATP channels was 110 micro
      m. This value was 3-fold higher than the IC50 in control myocytes (43 micro m).
      Treatment of hypothyroid rats to restore physiological levels of thyroid hormone
      (tri-iodothyronine, T3), resulted in a return to normal ATP-sensitivity (IC50 =
      46 micro M). In patches from animals rendered hyperthyroid, the IC50 for ATP was
      50 micro M and this value was not significantly different from the control. There
      was no difference in the cooperativity of ATP-binding (Hill coefficient, nH)
      among control (nH = 2.2), hypothyroid (nH = 2.1), T3-treated (nH = 2.0) and
      hyperthyroid groups (nH = 2.4). The unitary conductance was unchanged and there
      was no apparent change in intraburst kinetics between examples of single KATP
      channels from control and hypothyroid rats. Action potentials recorded in
      myocytes from hypothyroid rats were significantly shortened by 50 micro M
      levcromakalim, a KATP channel opener (P < 0.001) but unchanged in control
      myocytes.We conclude that hypothyroidism significantly decreased the ATP
      sensitivity of KATP channels, whereas the induction of hyperthyroid conditions
      did not alter the ATP-sensitivity of these channels. Thus, hypothyroidism is
      likely to have important physiological consequences under circumstances in which
      KATP channels are activated, such as during ischemia.

PMID- 9543495
TI  - Activators of epithelial Na+ channels inhibit cytosolic feedback control.
      Evidence for the existence of a G protein-coupled receptor for cytosolic Na+.
AB  - We have previously shown that epithelial Na+ channels in mouse mandibular gland
      duct cells are controlled by cytosolic Na+ and Cl-, acting, respectively, via Go
      and Gi proteins. Since we found no evidence for control of epithelial Na+
      channels by extracellular Na+ ([Na+]o), our findings conflicted with the long
      held belief that Na+ channel activators, such as sulfhydryl reagents, like para
      chloromercuriphenylsulfonate (PCMPS), and amiloride analogues, like
      benzimidazolylguanidinium (BIG) and 5-N-dimethylamiloride (DMA), induce their
      effects by blocking an extracellular channel site which otherwise inhibits
      channel activity in response to increasing [Na+]o. Instead, we now show that
      PCMPS acts by rendering epithelial Na+ channels refractory to inhibition by
      activated G proteins, thereby eliminating the inhibitory effects of cytosolic Na+
      and Cl- on Na+ channel activity. We also show that BIG, DMA, and amiloride
      itself, when applied from the cytosolic side of the plasma membrane, block
      feedback inhibition of Na+ channels by cytosolic Na+, while leaving inhibition by
      cytosolic Cl- unaffected. Since the inhibitory effects of BIG and amiloride are
      overcome by the inclusion of the activated alpha-subunit of Go in the pipette
      solution, we conclude that these agents act by blocking a previously unrecognized
      intracellular Na+ receptor.

PMID- 9543496
TI  - Effects of hyperosmolality on Na, K-ATPase gene expression in vascular smooth
      muscle cells.
AB  - Cultured vascular smooth muscle cells (VSMC) from rat thoracic aortas were
      exposed to hyperosmotic media to determine the effects on Na, K-ATPase alpha1-
      and beta1-mRNA expression. Hyperosmotic media (500 mOsm/kgH2O) supplemented with
      glucose or mannitol increased alpha1-mRNA levels threefold at 24 hr and beta1
      mRNA levels sevenfold at 12 hr. In sharp contrast, hyperosmotic urea medium had
      no effect at any time. Both the protein synthesis inhibitor cycloheximide and the
      RNA transcription inhibitor actinomycin D reduced alpha1- and beta1-mRNA
      upregulation induced by hyperosmotic glucose or mannitol media. Protein kinase C
      (PKC) inhibitors (staurosporine A or calphostin C) or tyrosine kinase (TK)
      inhibitors (genistein or herbimycin A) had no effect on the alpha1-mRNA
      upregulation induced by hyperosmotic glucose or mannitol media. Hyperosmotic
      glucose or mannitol media (500 mOsm/kgH2O) significantly increased alpha1- and
      beta1-subunit protein levels and Na, K-ATPase activity, whereas hyperosmotic urea
      medium had no effect. Transfection experiments with the 5'-flanking sequences of
      the alpha1- or beta1-subunit genes linked to the luciferase reporter gene
      revealed that hyperosmolar glucose medium increased luciferase activity 2.9- and
      3.7-fold, respectively. Similarly, hyperosmotic mannitol medium increased such
      activity 2.7- and 3.4-fold, respectively. These results demonstrate that: (i)
      hyperosmolality induced by the poorly permeating solutes (glucose and mannitol)
      stimulates alpha1- and beta1-mRNA accumulation, alpha1- and beta1-subunit protein
      accumulation, and Na, K-ATPase activity, whereas the rapidly permeating solute
      (urea) has no effect; (ii) the upregulation of alpha1- and beta1-mRNA in response
      to hyperosmotic glucose or mannitol media requires, at least in part, de novo
      synthesis of intermediate regulatory proteins; (iii) the hyperosmolality-induced
      alpha1-mRNA upregulation occurs through PKC- and TK-independent mechanisms,
      whereas the hyperosmolality-induced beta1-mRNA upregulation occurs through
      activation of PKC and TK; and (iv) hyperosmolality induced by glucose or mannitol
      increases promoter activities of the alpha1- and beta1-subunit genes.

PMID- 9543497
TI  - Phosphorylated carboxy terminal serine residues stabilize the mouse gap junction
      protein connexin45 against degradation.
AB  - Phosphoamino acid analysis of mouse connexin45 (Cx45) expressed in human HeLa
      cells revealed that phosphorylation occurred mainly at serine residues, but also
      on tyrosine and threonine residues. To characterize the role of Cx45
      phosphorylation, different serine residues of the serine-rich carboxy terminal
      region were deleted or exchanged for other amino acids residues. Human HeLa cells
      deficient in gap junctional intercellular communication were stably transfected
      with appropriate constructs and analyzed for expression, localization,
      phosphorylation, formation of functional gap junction channels and degradation of
      mutant Cx45. fter exchange or deletion of nine carboxy terminal serine residues,
      phosphorylation was decreased by 90%, indicating that these serine residues
      represented main phosphorylation sites of mouse Cx45. The various serine residues
      of this region contributed differently to the phosphorylation of Cx45 suggesting
      a cooperative mechanism for phosphorylation. Substitution of different serine
      residues for other amino acids did not interfere with correct intracellular
      trafficking and assembly of functional gap junction channels, as shown by
      localization of mutant Cx45 at the plasma membrane and by dye transfer to
      neighboring cells. Truncated Cx45 was also weakly phosphorylated but was trapped
      in perinuclear locations. Dye transfer of these transfectants was similar as in
      nontransfected HeLa cells. The half-life of mouse Cx45 protein in HeLa cells was
      determined as 4.2 hr. Pulse-chase experiments with the different transfectants
      revealed an increased turnover of Cx45, when one or both of the serine residues
      at positions 381 and 382 or 384 and 385 were exchanged for other amino acids. The
      half-life of these mutants was diminished by 50% compared to wild type Cx45.

PMID- 9543499
TI  - The Extent of Benthic Impacts of CCA-Treated Wood Structures in Atlantic Coast
      Estuaries
AB  - To ascertain the extent of impacts from CCA-treated wood bulkheads, we sampled
      sediments along 10-m transects from these bulkheads and from reference sites
      (either bulkheads made of other materials or unbulkheaded areas nearby) and
      analyzed the fine fraction for metals. We ascertained metal content in resident
      biota, and analyzed species richness, Shannon-Wiener diversity index, and biomass
      of the benthic community. We found accumulation of metals in the fine-grained
      portion of nearby sediments and reduction in the biotic community nearby
      (generally at 0 and 1 m); such gradients were generally not seen in reference
      transects. At two of the sites there was evidence for secondary reduction of the
      community out further to 3 or 10 m, where the metals in the fines were lower but
      the percent fines was greatly increased. At all the other sites, impacts were
      generally limited to 0 and 1 m. The lack of reduction at further distances at the
      other sites is attributed to factors such as the age of the bulkheads, high
      energy of the environment, or nature of the sediments at those sites.

PMID- 9543498
TI  - Interactions of primary amphipathic vector peptides with membranes.
      Conformational consequences and influence on cellular localization.
AB  - The conformations of two peptides produced by the combinations of a nuclear
      localization sequence and a sequence issued from the fusion protein gp41 of HIV 1
      have been analyzed both in solution and in membranes or in membrane mimicking
      environments. Both are shown to be nonordered in water, alpha-helical when
      incorporated into SDS micelles where the helical domain concerns the hydrophobic
      part of the peptides. Interactions with lipids induce the formation of beta-sheet
      and the lipid-peptide interactions are governed by the nature of the lipid polar
      headgroups. A monolayer study shows that replacement of the sequence separating
      the two sequences with an arginine favors the lipid-peptide interactions which
      may contribute to the understanding of the different, nuclear and membrane
      associated, cellular localizations of the peptides.

PMID- 9543500
TI  - The Fate of Elements in Residential Composters
AB  - An investigation into the fate of elements during residential composting was
      conducted by studying an Envirocycle residential-type aerobic composter unit that
      was set up and operated at the University of Toronto's greenhouse facility.
      Source materials consisting of various fruits and vegetables were combined with
      Metropolitan Toronto Works Department's finished leaf compost (MWFLC), and
      composted over a 2-month period. Instrumental neutron activation analysis (INAA)
      was used to determine the concentrations of Al, As, Ba, Ca, Co, Cr, Fe, K, Mg,
      Mn, Na, Sb, Sr, Ti, V, and Zn in the source materials and the 2-month greenhouse
      finished compost (GHFC). Results indicate that the ratio of final element mass to
      input element mass was approximately 1, suggesting that elements are conserved
      during the composting process. One tailed t tests (0.05 level of significance) on
      element concentrations between the MWFLC and GHFC revealed that supplementing
      MWFLC with fruits and vegetables does not significantly change concentrations
      >25%. One-way analyses of variances conducted on Toronto residential compost
      samples revealed good homogeneity within an individual composter, although
      significant elemental variances occurred between separate composters.
      Incidentally, it was noticed that several of the Toronto residential compost
      samples had Cr levels that exceeded Ontario Ministry of Environment and Energy
      guideline values for municipal compost.

PMID- 9543501
TI  - Lead content in edible wild mushrooms in northwest Spain as indicator of
      environmental contamination.
AB  - Lead content was determined in wild growing mushrooms collected from two
      different areas in the Province of Lugo (NW Spain). It has been analyzed by
      graphite furnace atomic absorption spectrometry in 95 samples of 13 species (7
      mycorrhizals and 6 saprophites). In an assessment of lead concentrations, the
      following factors have been considered: species and ecology, morphological
      portion, and traffic pollution. The average lead concentration of the samples was
      1 ppm dry weight (dw). Saprophite species presented higher levels than
      mycorrhizal ones (< 1 ppm), Coprinus comatus reaching the maximum mean
      concentration with 2.06 and 2.79 ppm of dw in the hymenophore and the rest of the
      fruit body. Morphological portion, statistically, did not show significant
      difference between the two portions; however, Macrolepiota procera always
      presented lead high levels in the hymenophore in all samples. The effect due to
      traffic pollution has been specially observed in Coprinus comatus, presenting the
      highest concentration with values of 6.51 and 10.43 ppm, respectively, in samples
      collected in the city center. This species, as other researchers have indicated,
      could be considered as an indicator by lead contamination. The contribution of
      mushrooms to the weekly intake of lead was calculated and the possible health
      risk for the consumer is pointed out. These data are of great importance in view
      of toxicology and partly environmental protection.

PMID- 9543502
TI  - In Situ Investigation of Trace Metal Availability in Industrial Effluents Using
      Transplanted Aquatic Mosses
AB  - Three species of aquatic mosses, Rhynchostegium riparioides, Fontinalis
      antipyretica, and Cinclidotus danubicus, were collected from the same reference
      location and exposed in five industrial effluents. The purpose was to test their
      suitability for assessing trace metal contamination under adverse and contrasted
      environmental conditions. Two distinct experiments of 16 and 11 days were
      conducted. In spite of short residence times in the effluents, the bryophytes
      were considerably affected at several sites, showing a light green to yellowish
      color, brown-edged leaves, and even dead strands. Cinclidotus danubicus was the
      most resistant whereas Fontinalis antipyretica was the most sensitive species.
      The observed physiological damage had no obvious incidence on the accumulation
      capacity of the mosses. The biomonitors provided time-integrated patterns of
      trace metal bioavailability (copper, chromium, nickel, lead, and zinc) in the
      effluents with a clear discrimination between poorly, moderately, and heavily
      polluted sites. Compared to water analyses, these more reliable indications could
      be obtained with a considerably reduced sampling design. When substantial
      accumulation occurred in mosses, the highest concentrations were systematically
      found in Rhynchostegium riparioides and the lowest in Cinclidotus danubicus. As
      only quantitative, not qualitative, differences were observed, all investigated
      moss species can be recommended for the assessment of trace metals in effluents
      at their discharge into the natural environment.

PMID- 9543503
TI  - Inertia and Resilience in the Responses of the Aquatic Bryophyte Fontinalis
      antipyretica Hedw. to Thermal Stress
AB  - The physiological responses of the aquatic bryophyte Fontinalis antipyretica
      Hedw. to high temperatures, ranging from 16 degreesC (control) to 34 degreesC,
      were investigated experimentally. Plant samples were maintained at the
      temperature under study for up to 25 days with regular determination of
      physiological variables (pigment ratio and photosynthetic and respiratory rates).
      Physiological responses to temperature did not differ significantly between
      mosses collected from a normal river site and from a river site with abnormally
      high temperature due to input from a hot spring. Simple curve-fitting procedures
      and summary statistics analogous to those used in toxicological research were
      employed to compare responses as revealed by the different physiological
      variables. In a second series of experiments, the capacity of F. antipyretica to
      recover from high-temperature stress was investigated by maintaining samples at
      30 degreesC for 2, 4, or 10 days, then transferring the samples to normal
      conditions (16 degreesC) for 40 days. Physiological variables were again
      monitored at regular intervals throughout both phases of the experiment. In
      general, good recovery was observed even after exposure to high temperatures for
      10 days. The results of these assays allow quantification of the relationship
      between a pigment ratio and net photosynthesis rate.

PMID- 9543504
TI  - Ecotoxicity Assessment of Contaminated Dredged Material with the Marine Amphipod
      Corophium volutator
AB  - The incorporation of toxicological data from bioassays can improve the present
      system of sediment quality criteria in the Netherlands. The use of acute
      lethality toxicity tests alone does not however provide sufficient discrimination
      and sensitivity for predicting ecological effects of slightly and moderately
      contaminated dredged material. Sublethal endpoints are needed for the assessment
      of environmental hazards of such dredged material. In this study, two approaches
      were used to identify toxicity of marine sediments collected from 16 locations
      classified as "slightly and moderately contaminated" on the basis of chemical
      data: (1) a comparison of growth vs. mortality as different endpoints in the
      marine amphipod Corophium volutator (Pallas); (2) an investigation on the use of
      sediment dilutions to characterize the degree of toxicity. The influence of
      sediment storage time on toxicity was also evaluated. In four out of 16
      locations, mortality over 10 days of exposure ranged 80-100%; in two out of 16
      locations mortality ranged 40-60%. In the other 10 locations, mortality was below
      15%. Results on growth showed that in all locations final dry weight values were
      significantly lower (a factor of 1.5 to 3) than in controls. Results of dilution
      experiments showed that if sediments were diluted with a reference sediment of
      similar physicochemical characteristics, total concentrations of metals, mineral
      oil, and PAHs decreased as expected and so did the effects on C. volutator. In
      the 100% contaminated sediments growth was reduced by 32-60% compared to
      controls. The dilution rate necessary to reduce toxicity to the EC10 value for
      growth of C. volutator was considered an appropriate endpoint for the evaluation.
      When sediments were stored for a period of 3-5 months at 4 degreesC and retested,
      effects on mortality and growth decreased, although some effects on growth were
      still measured after 5 months of storage. The experiments illustrate the
      usefulness of ecotoxicity assessment to evaluate contaminted dredged material.

PMID- 9543505
TI  - Bioassays using the midge Chironomus riparius and the zebra mussel Dreissena
      polymorpha for evaluation of river water quality.
AB  - To evaluate if the water quality of the river Meuse affects macrofauna species,
      the impact of water from this river on two representative species was tested
      under controlled conditions. Short-term bioassays with reference populations of
      the midge Chironomus riparius and the zebra mussel Dreissena polymorpha were
      performed simultaneously, using growth and filtration rate as sublethal
      parameters, respectively. Filtration rates of mussels seemed to be slightly
      inhibited by Meuse water in 1994 and 1995, although this was only significant in
      the first year. Apparently, although this species is inhabiting the river Meuse,
      the water quality still causes sublethal effects. In contrast to the mussel,
      midges were less sensitive to Meuse water in laboratory experiments; growth
      inhibition was never observed, while in some experiments growth was even
      enhanced. In the period of testing, it was not possible to relate effects on
      macrofauna species in laboratory tests to individual substances in polluted river
      systems. Because the response of the test species was marginal, it is recommended
      to include more sensitive species as tested in the present study, especially in
      view of a general improvement of the water quality in the river Meuse.

PMID- 9543506
TI  - Paraquat tolerance and alteration of internal gill structure of Scinax nasica
      tadpoles (Anura: Hylidae).
AB  - Paraquat acute tolerance, and histological and ultrastructural response analysis
      of gills were evaluated in Scinax nasica tadpoles at stages 25-26. The treated
      tadpoles were able to survive with a mortality rate similar to the controls in
      media containing 6.48 to 10.80 mg PQ/L. At 18.00 mg PQ/L survival rate was about
      85%; at 30.00 and 50.00 mg PQ/L an incremented mortality rate was detected. Their
      internal gills appear to have a critical role in adaptation to exposure to PQ.
      The LC-50 values found helped us conclude that increasing time of exposure to PQ
      produces a decrease of tadpole survival rate. With light microscopy, the apical
      ramification gill tufts exhibited a dose response increase of the total volume.
      At the ultrastructural level, an increase in the intercellular spaces and
      alteration in gill epithelium organization were the most notable changes.
      Furthermore, the capillaries showed enlarged endothelial cells, irregular nuclei,
      and numerous cytoplasmatic projections.

PMID- 9543507
TI  - Comparative toxicity of diuron on survival and growth of Pacific treefrog,
      bullfrog, red-legged frog, and African clawed frog embryos and tadpoles.
AB  - The effects of the herbicide diuron on survival and growth of Pacific treefrog
      (Pseudacris regilla), bullfrog (Rana catesbeiana), red-legged frog (Rana aurora),
      and African clawed frog (Xenopus laevis) embryos and tadpoles were determined in
      static-renewal tests. P. regilla and X. laevis embryos had reduced growth and
      developed increased deformities in diuron concentrations over 20 mg/L. Hindlimb
      bud and forelimb development were retarded in R. aurora following 14 days
      exposure to diuron concentrations of > 7.6 mg/L. Mean 14-day LC50s for P. regilla
      and X. laevis tadpoles were 15.2 and 11.3 mg/L diuron, respectively. The 21-day
      LC50 for R. catesbeiana tadpoles was 12.7 mg/L diuron. The 14-day LC50 for R.
      aurora tadpoles was 22.2 mg/L. The lowest NOAELs calculated in embryo tests were
      14.5 mg/L for P. regilla (10 days) and 7.6 mg/L diuron for X. laevis (4 days).
      The lowest NOAELs calculated in tadpole tests were: P. regilla, 14.5 mg/L (14
      days); R. catesbeiana, 7.6 mg/L (21 days); R. aurora, 7.6 mg/L (14 days); and X.
      laevis, > 29.1 mg/L (14 days). Diuron concentrations having an effect on
      survival, growth, and malformation in the laboratory were much higher than those
      found in normal field spray situations; field studies would be needed to
      determine the hazard to amphibians in areas of localized pooling of recently
      applied herbicide in the environment.

PMID- 9543508
TI  - Effects of subchronic exposure to cadmium chloride on endocrine and metabolic
      functions in rainbow trout Oncorhynchus mykiss.
AB  - Adult and juvenile rainbow trout, Oncorhynchus mykiss, were exposed for 30 days
      to CdCl2 in water (10 and 25 micrograms Cd/L for adults, and 1 and 5 micrograms
      Cd/L for juveniles) to investigate effects of subchronic exposures to Cd on the
      hypothalamo-pituitary-interrenal and the hypothalamo-pituitary-thyroid axis, and
      on metabolic status. liver size and glycogen content and body mass gain were
      significantly reduced in the exposed adult fish and similar changes were detected
      in the juveniles. Plasma cortisol levels increased after exposure to the lower
      dose but decreased at the higher dose. Plasma T3 and T4 tended to decrease in the
      exposed adult fish. No significant differences in plasma glucose or cholesterol
      levels were detected between the controls and the exposed fish, plasma calcium
      levels were lower in the exposed fish. The results indicate that long-term
      exposures to Cd at sublethal doses have adverse effects on the physiological
      status of the fish and that these effects are mediated partly through alterations
      of endocrine function.

PMID- 9543509
TI  - Trace elements in egg contents and egg shells of slider turtles (Trachemys
      scripta) from the Savannah River Site.
AB  - In this paper we examine the levels of trace elements in the egg contents and egg
      shells of slider turtles (Trachemys scripta) from the Savannah River Site, near
      Aiken, South Carolina. Trace elements have seldom been examined in the tissues or
      eggs of reptiles, although some turtles and large snakes occupy a high trophic
      level. Lead, mercury, cadmium, selenium, chromium, and manganese levels were
      examined in one egg and its egg shell collected from each of 16 females that laid
      in late May and June 1996. We were interested in determining background levels,
      whether certain metals were sequestered in the egg shells, and whether levels
      were higher in contents or shells. Concentrations were higher in egg contents
      than in shells for lead, mercury, and selenium, while chromium was higher in the
      shell. There were no differences for cadmium and manganese. Compared to eggs from
      other reptiles, levels in slider turtles were generally similar for cadmium and
      selenium, lower for chromium and lead, and higher for manganese.

PMID- 9543510
TI  - Accumulation Features of Polychlorinated Biphenyls and Organochlorine Pesticides
      in Resident and Migratory Birds from South India
AB  - Persistent organochlorines such as DDT and its metabolites (DDTs),
      hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs),
      hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs) were determined in
      whole-body homogenates of resident and migratory birds collected from South
      India. Organochlorine contamination pattern in birds varied depending on their
      migratory behaviour. Resident birds contained relatively greater concentrations
      of HCHs (14-8,800 ng/g wet wt) than DDTs and PCBs concentrations. In contrast,
      migrants exhibited elevated concentrations of PCBs (20-4,400 ng/g wet wt). The
      sex differences in concentrations and burdens of organochlorines in birds were
      pronounced, with females containing lower levels than males. Inland piscivores
      and scavengers accumulated greater concentrations of HCHs and DDTs while coastal
      piscivores contained comparable or greater amounts of PCBs. Global comparison of
      organochlorine concentrations indicated that resident birds in India had the
      highest residues of HCHs and moderate to high residues of DDTs. It is, therefore,
      proposed that migratory birds wintering in India acquire considerable amounts of
      HCHs and DDTs. Estimates of hazards associated with organochlorine levels in
      resident and migratory birds in India suggested that Pond Heron, Little Ringed
      Plover, and Terek Sandpiper may be at risk from exposure to DDTs.

PMID- 9543511
TI  - Dietary Exposure to Mercury in Nestling Wood Storks (Mycteria americana) in
      Georgia
AB  - The United States breeding population of the wood stork (Mycteria americana) was
      listed as endangered in 1984; the U.S. Fish and Wildlife Service has listed the
      determination of potential contaminant hazards as a task important to the
      recovery of the species. Storks nest in colonies and adult storks forage over
      wide areas and return with prey items to feed to nestlings. The most recently
      consumed prey items are usually regurgitated by nestlings when they are handled.
      In 1995, over 200 food items from four wood stork colonies were collected while
      banding nestlings between 20 and 40 days old, and total mercury determined in
      individual food items. Two colonies were located on the Atlantic coast and two in
      inland areas. Overall dietary mercury concentration for each colony was
      calculated based on the biomass of each type of food item within the diet.
      Freshwater prey items had higher mercury concentrations than saltwater items most
      frequently chosen by storks. Daily Hg doses were estimated for a range of
      nestling sizes and daily food consumption rates. Risk factors were calculated
      based on two lowest observable adverse effect concentrations (LOAECs) from
      previous avian mercury ingestion studies. Based on one LOAEC, all four colonies
      in this study were at risk of sublethal effects due to mercury in the diet of
      nestling wood storks. More extensive studies of sublethal effects in avian
      species from mercury contamination are necessary for more accurate risk
      assessment.

PMID- 9543512
TI  - Organochlorine and heavy metal contaminants in wild mink in western Northwest
      Territories, Canada.
AB  - The mink (Mustela vision) is a top trophic level species that readily
      bioaccumulates environmental pollutants and is considered to be a sensitive
      indicator of ecosystem health. Spatial trends in levels of organochlorine and
      heavy metal contaminant burdens were determined from 1991 to 1995 for wild mink
      from western Northwest Territories (NWT), Canada. Tissue samples from 207 mink
      from seven communities were analyzed for residues of 63 organochlorines and 10
      heavy metals. All groups of organochlorines were detected in mink livers at
      relatively low levels; maximum community means were 9.52 ng/g sigma DDT and 73.07
      ng/g sigma PCB (sum of 43 congeners). There was a general trend of decreasing
      organochlorine burdens along a northerly or westerly gradient for some groups of
      compounds, primarily sigma DDT, sigma PCB, sigma chlordane and dieldrin. Toxic
      equivalents (TEQs) of mink liver tissue were low, with the maximum community mean
      of 0.28 pg/g wet weight (5.5 pg/g lipid weight). Levels of heavy metal burdens in
      liver and kidney tissues were found to be relatively low, with the exception of
      Hg, which was found at moderate levels. There was no obvious geographic trend to
      the pattern of heavy metal burdens. The available evidence suggests that long
      range atmospheric transport is the main source of the organochlorine contaminants
      observed. Local conditions (geology, water and soil chemistry, diet, etc.) may
      determine heavy metal burdens. Levels of contaminants in NWT mink appear to be
      one to two orders of magnitude lower than levels observed to cause reproductive
      impairment, reduced survival of kits, or lethality in adult mink. In the western
      NWT mink may be the best indicator to assess trends in environmental contaminants
      and ecosystem health; periodic monitoring is recommended.

PMID- 9543514
TI  - Anouncements

PMID- 9543513
TI  - Polychlorinated naphthalenes and other organochlorine contaminants in Swedish
      human milk, 1972-1992.
AB  - The concentrations of polychlorinated naphthalenes (PCNs) were determined
      together with polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs),
      dibenzofurans (PCDFs), 1,1-bis-(4-chlorophenyl)-2,2,2-trichloroethane (p,p'-DDT),
      2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) and hexachlorobenzene
      (HCB) in milk, sampled in the course of 1972-92 from mothers living in Stockholm.
      A previously developed method for multicomponent analysis of organochlorine
      environmental contaminants was adapted for simultaneous analysis of PCNs. The
      mean recoveries of seven chlorinated naphthalene (CN) congeners added to milk
      prior to extraction were 76-99%. Similar recoveries were obtained for the
      commercial PCN product Halowax 1014. The pattern of PCNs in milk differed to a
      great extent from that in the commercial PCN products. The dominating congeners
      in breast milk were 1,2,3,5,7-pentachloronaphthalene (CN-52), 1,2,3,4,6,7- and/or
      1,2,3,5,6,7-hexachloronaphthalene (CN-66/ CN-67) and one unidentified
      tetrachloronaphthalene. There was a notable decrease in the concentrations of
      PCNs as was of the other organochlorine contaminants in milk from 1972 to 1992.
      During this time period the sum of CN congeners decreased from 3,081 to 483 pg/g
      milk fat and the sum of toxic equivalents of dioxin and dioxin-like compounds
      decreased from 100 to 39 pg/g milk fat.

PMID- 9543515
TI  - Complications of laparoscopic cholecystectomy.

PMID- 9543516
TI  - Biliary tract complications in laparoscopic cholecystectomy. A multicenter study
      of 148 biliary tract injuries in 26,440 operations.
AB  - BACKGROUND: The higher risk of biliary tract injury is considered the most
      significant disadvantage of laparoscopic cholecystectomy. METHODS: A national
      multicenter retrospective study was performed to determine the frequency,
      etiology, and treatment of biliary tract injuries between January 1, 1991, and
      December 31, 1994. Follow-up was by questionnaire. RESULTS: Some 148 biliary
      tract complications were observed during 26,440 laparoscopic cholecystectomies.
      There was no significant correlation found between the number of LCs performed in
      one institute and the incidence of biliary tract injuries and postoperative bile
      leakage, but in the 2nd year of practice, the incidence of both complications
      decreased. In institutes with more conversions, more cases of bile leakage were
      also observed. A significant positive relationship was found between biliary
      tract injuries and postoperative bile leaks. There was no significant
      relationship between usage of intravenous and intraoperative cholangiography and
      ERCP. In univariant analysis of the type of injury, the primary treatment
      modality did not affect the outcome of injury or entail the necessity of
      reoperation. Obscure anatomy leads to significantly more main bile duct injuries.
      According to multivariant analysis, the outcome is significantly influenced
      unfavorably by the necessity of repeated interventions and advanced age.
      CONCLUSIONS: The definitely higher risk of bile duct injury mentioned in early
      studies was not confirmed.

PMID- 9543517
TI  - Laparoscopic endobiliary stenting as an adjunct to common bile duct exploration.
AB  - BACKGROUND: The management of common bile duct stones (CBDS) in the era of
      operative laparoscopy is evolving. Several minimally invasive techniques to
      remove CBDS have been described, including preoperative endoscopic retrograde
      cholangiopancreatography (ERCP), postoperative ERCP, lithotripsy, laparoscopic
      transcystic common bile duct exploration, and laparoscopic choledochotomy with
      common bile duct exploration (CBDE). Because of the risks and limitations of
      these procedures, we utilize laparoscopically placed endobiliary stents as an
      adjunct to CBDE. METHODS: Sixteen patients underwent laparoscopic common bile
      duct exploration (LCBDE) by either choledochotomy or the transcystic technique
      with placement of endobiliary stents. These patients were identified during
      laparoscopic cholecystectomy as having occult choledocholithiasis, using routine
      dynamic intraoperative cholangiography. RESULTS: CBDS were successfully removed
      in all patients as demonstrated by completion cholangiography and intraoperative
      choledochoscopy. Eighty percent of patients were discharged the following day;
      the first three patients in this series were observed for 48 h prior to
      discharge. No patient required T-tube placement and closed suction drains were
      removed the morning after surgery. Stents were removed endoscopically at 1 month.
      Six- to 30-month follow-up demonstrates no complications to date. CONCLUSIONS:
      Laparoscopic endobiliary stenting reduces operative morbidity, eliminates the
      complications of T-tubes, and allows patients to return to unrestricted activity
      quickly. We recommend laparoscopically placed endobiliary stents in patients
      undergoing LCBDE.

PMID- 9543518
TI  - Spilled gallstones after laparoscopic cholecystectomy. A relevant problem? A
      retrospective analysis of 10,174 laparoscopic cholecystectomies.
AB  - BACKGROUND: Spilled gallstones after laparoscopic cholecystectomy may cause
      abscess formation, but the exact extent of this problem remains unclear. METHOD:
      The data (collected by the Swiss Association of Laparoscopic and Thoracoscopic
      Surgery) on 10,174 patients undergoing laparoscopic cholecystectomy at 82
      surgical institutions in Switzerland between January 1992 and April 1995 were
      retrospectively analyzed with special interest in spilled gallstones and their
      complications. RESULTS: In 581 cases (5.7%) spillage of gallstones occurred; 34
      of these cases were primarily converted to an open procedure for stone retrieval.
      Of the remaining 547 cases only eight patients (0.08%) developed postoperatively
      abscess formation requiring reoperation. CONCLUSIONS: Spillage of gallstones
      after laparoscopic cholecystectomy is fairly common and occurs in about 6% of
      patients. However, abscess formation with subsequent surgical therapy remains a
      minor problem. Removal of spilled gallstones is therefore not recommended for all
      patients, but an attempt at removal should be performed whenever possible.

PMID- 9543519
TI  - Common bile duct injuries during laparoscopic cholecystectomy that result in
      litigation.
AB  - BACKGROUND: Iatrogenic common bile duct injury is the worst complication of
      laparoscopic cholecystectomy. The goal of this study is to increase awareness of
      the problem and educate surgeons about the consequences of these injuries.
      METHODS: A total of 46 bile duct injuries were analyzed by review of medical
      records, cholangiograms, videotapes, and surgeon statements. All cases were
      involved in malpractice litigation. RESULTS: All types of injuries were
      represented. There were 15 transections, 11 excisions, 6 lacerations, 8 clip
      impingements, 3 burns, 2 bile leaks, and 1 cystic duct leak. In all, 72% of these
      injuries occurred in elective cases in which there was no acute inflammation.
      Cholangiograms were performed in 16 cases, but they were misinterpreted in 11 of
      them. Injury type and severity was similar in patients with and without
      cholangiography. A total of 80% of these injuries were not detected at the
      initial surgery. The average delay in diagnosis was 10 days. Complications were
      worse in patients with delayed diagnosis. Primary surgeons had less successful
      outcomes from repairs than referral surgeons (27% versus 79%). In 86% of cases,
      litigation was resolved in favor of plaintiffs by settlement or verdicts. The
      average award was $214,000. CONCLUSIONS: Factors that predispose to lawsuits
      include treatment failures in immediately recognized injuries, complications that
      result from delays in diagnosis, and misinterpretation of abnormal
      cholangiograms. Injury prevention can be improved by increased awareness of
      common mistakes,. Improved cholangiographic technique and interpretation should
      decrease injury severity, delays in diagnosis, and subsequent morbidity.

PMID- 9543520
TI  - Bile duct injury after laparoscopic cholecystectomy. The United States
      experience.
AB  - BACKGROUND: Forty series reporting experience with laparoscopic cholecystectomy
      in the United States from 1989 to 1995 were reviewed. A total of 114,005 cases
      were analyzed and 561 major bile duct injuries (0.50%) and 401 bile leaks from
      the cystic duct or liver bed (0.38%) were recorded. Intraoperative
      cholangiography (IOC) was attempted in 41.5% of the laparoscopic
      cholecystectomies and was successful in 82.7%. In major bile duct injuries, the
      common bile duct/common hepatic duct were the most frequently injured (61.1%) and
      only 1.4% of the patients had complete transection. METHODS: When reported, most
      of the bile duct injuries were managed surgically with a biliary-enteric
      anastomosis (41.8%) or via laparotomy and t-tube or stent placement (27.5%). The
      long-term success rate could not be determined because of the small number of
      series reporting this information. The management for bile leaks usually
      consisted of a drainage procedure (55.3%) performed endoscopically
      percutaneously, or operatively. RESULTS: The morbidity for laparoscopic
      cholecystectomy, excluding bile duct injuries or leaks, was 5.4% and the overall
      mortality was 0.06%. It was also noted that the conversion rate to an open
      procedure was 2.16%. CONCLUSIONS: It is concluded based on this review of
      laparoscopic cholecystectomies that the morbidity and mortality rates are similar
      to open surgery. In addition, the rate of bile duct injuries and leaks is higher
      than in open cholecystectomy. Furthermore, bile duct injuries can be minimized by
      lateral retraction of the gallbladder neck and careful dissection of Calot's
      triangle, the cystic duct-gallbladder junction, and the cystic duct-common bile
      duct junction.

PMID- 9543521
TI  - How, when, and why bile duct injury occurs. A comparison between open and
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Bile duct injury (BDI) is a severe complication of laparoscopic
      cholecystectomy (LC). There is general agreement about the increase of this
      complication after LC vs open cholecystectomy (OC), but comparative studies are
      scarce. The aim of this paper has been to compare the incidence and clinical
      features of BDI after LC vs open procedures. MATERIALS AND METHODS: 3,051 OC,
      performed from June 1977 to December 1988 were retrospectively analyzed and
      compared with 1,630 LCs performed from June 91 to August 96, for which data were
      prospectively recorded. Age, sex, type of BDI, performance of intraoperative
      cholangiography (IOC), underlying biliary pathology, morbidity, mortality, and
      late morbidity were all analyzed. RESULTS: BDI incidence was higher in group II
      (LC) (N: 16, 0.95%) than in group I, (OC, N: 19. 0.6%). BDI incidence was also
      higher in the group of patients in which it was necessary to convert to an open
      procedure (3/109, 2.7%, p < 0.05). BDIs were more frequently diagnosed
      intraoperatively in group I (OC, 18/19) than in group II (LC, 12/16). In both
      groups, BDI was more prevalent in cases operated by staff surgeons than
      residents, mainly in complicated gallbladder patients, with a bile duct of less
      than 7-mm diameter. Morbidity, postoperative stay, mortality, and late morbidity
      were similar after a BDI in both types of approach. CONCLUSIONS: (1) BDI
      increases with LC. (2) BDI after LC carries a similar postoperative morbidity and
      mortality to those after OC. (3) Incidence of BDI in converted cases increases
      significantly and this constitutes a high-risk group.

PMID- 9543522
TI  - Biliary stenting is more effective than sphincterotomy in the resolution of
      biliary leaks.
AB  - BACKGROUND: Biliary fistulae may occur following surgical injury, abdominal
      trauma, or inadequate closure of a cystic duct stump. These leaks are most often
      managed by drainage of the associate biloma and either endoscopic sphincterotomy
      or placement of a biliary endoprosthesis to decrease the pressure gradient
      between the bile duct and the duodenum created by the muscular contraction of the
      ampullary sphincter. In a previous study, we demonstrated a statistically
      significant reduction in ductal pressures following stent placement as compared
      to sphincterotomy. The goal of this present study was to determine if reduction
      in ductal pressures correlates clinically with the resolution of biliary leaks in
      an animal model. METHODS: Fourteen mongrel dogs underwent laparotomy,
      cholecystectomy without closure of the cystic stump, and a lateral duodenotomy to
      identify the major papilla. The dogs were then randomized into three groups.
      Group I (n = 5) was a control group undergoing closure of the duodenotomy only.
      Group II (n = 4) underwent sphincterotomy. Group III (n = 5) underwent placement
      of a 7 Fr x 5 cm biliary endoprosthesis prior to duodenotomy closure. A drain was
      placed adjacent to the cystic duct stump in all groups. Drain output was recorded
      daily. The biliary leak was considered resolved when the output was < 10 cc/day.
      Regardless of suspected fistula closure, the drains were not removed until 2
      weeks postprocedure. Necropsy was performed to identify undrained intraperitoneal
      bile. Statistical analysis was performed using Student's paired t test. RESULTS:
      All dogs had bile leaks identified on postoperative day 1. The number of days
      required for resolution of bile leak in group I (mean +/- SEM) was 7.60 +/- 0.87
      days, as compared to 6.75 +/- 0.80 days for group II and 2.60 +/- 0.24 days for
      group III. There was no significant difference in the duration of bile leak
      between groups I and II (p = 0.445). Group III, however, had a significant
      reduction in the duration of biliary fistulae as compared to both groups I and II
      (p < 0.005). At autopsy, persistent bilomas were identified in 80% of group I,
      25% of group II, and 0% of group III. None of the dogs showed evidence of
      dehisence of the duodenotomy closure site as a source of bile leak. CONCLUSION:
      Biliary stenting significantly reduces the time to resolution of cystic duct
      leaks as compared to sphincterotomy in a canine model. The results obtained in
      this study support the use of biliary endoprostheses in the management of biliary
      leaks and fistulae.

PMID- 9543523
TI  - Laparoscopic liver surgery. A report on 28 patients.
AB  - BACKGROUND: An effort was made to evaluate the indications, safety, and
      therapeutic efficacy of laparoscopic liver surgery. METHODS: Between 1989 and
      1996, 28 patients, 23 to 88 years old were operated upon laparoscopically.
      Pathology consisted of simple cyst (ten), polycystic liver disease (seven),
      hydatid cyst (three, two of them calcified), abscess (one), focal nodular
      hyperplasia (six), and metastatic breast cancer (one). RESULTS: Operations
      included 17 fenestrations, three pericystectomies, and eight resections (two
      lateral lobes). Operative time was 45 to 525 min with only four cases longer than
      4 h. There was a 21% morbidity rate. There were no mortalities. Follow-up was 1
      67 months with one asymptomatic recurrence. CONCLUSIONS: Laparoscopic hepatic
      surgery can be performed safely with good results by surgeons with hepatic and
      laparoscopic experience when careful selection criteria are followed. We advocate
      the "four-hands technique" for simultaneous dissection and control of bleeding
      and bile ducts during resections.

PMID- 9543524
TI  - Total radiated power, infrared output, and heat generation by cold light sources
      at the distal end of endoscopes and fiber optic bundle of light cables.
AB  - BACKGROUND: Skin burns and ignition of drapes have been reported with the use of
      cold light sources. The aim of the study was to document the temperature
      generated by cold light sources and to correlate this with the total radiated
      power and infrared output. METHODS: The temperature, total radiated power, and
      infrared output were measured as a function of time at the end of the endoscope
      (which is inserted into the operative field) and the end of the fiber optic
      bundle of the light cable (which connects the cable to the light port of the
      endoscope) using halogen and xenon light sources. RESULTS: The highest
      temperature recorded at the end of the endoscope was 95 degrees C. The
      temperature measured at the optical fiber location of the endoscope was higher
      than at its lens surface (p < 0.0001). At the end of the fiber optic bundle of
      light cables, the temperature reached 225 degrees C within 15 s. The temperature
      recorded at the optical fiber location of all endoscopes and light cables studied
      rose significantly over a period of 10 min to reach its maximum (p <0.0001) and
      then leveled off for the duration of the study (30 min). The infrared output
      accounted only for 10% of the total radiated power. CONCLUSIONS: High
      temperatures are reached by 10 min at the end of fiber optic bundle of light
      cables and endoscopes with both halogen and xenon light sources. This heat
      generation is largely due to the radiated power in the visible light spectrum.

PMID- 9543525
TI  - Bilateral thoracoscopic stapled volume reduction for bullous vs diffuse
      emphysema.
AB  - BACKGROUND: We compared our results with bullous vs diffuse emphysema by
      performing a bilateral thoracoscopic stapled volume reduction technique in 15
      patients (age 45-80, 10 males, five females). METHODS: Eight patients
      demonstrated bullous emphysema and seven patients diffuse emphysema. Lung
      reduction was performed with a bilateral thoracoscopic stapled technique
      utilizing bovine pericardium in the supine position. RESULTS: Comparison of the
      bullous versus diffuse groups revealed no significant differences in means for
      the following variables: length of air leak (7.5 vs 3.3 days); length of stay
      (8.1 vs 6.5 days); pre-op FEV1, (23% vs 22%); pre-op dyspnea index (3.4 vs 3.6).
      At 3 months the bullous subset had a highly significant improvement (p < 0.007)
      in FEV1 (88%) compared with the diffuse subset FEV1 (59%). CONCLUSIONS: These
      early results suggest that patients with bullous emphysema are at no greater risk
      and demonstrate a significantly greater improvement in FEV1 than patients with
      diffuse emphysema.

PMID- 9543526
TI  - Ultrasonic epithelial ablation of the lower esophagus without stricture
      formation. A new technique for Barrett's ablation.
AB  - BACKGROUND: The premalignant potential of Barrett's esophagus has stimulated
      efforts to find a way to ablate the columnar epithelium in order to reheal the
      area with squamous epithelium, thus obviating the cancer risk. This study
      describes and evaluates a new technique using ultrasonic energy to ablate the
      epithelium of the lower esophagus in a porcine model. METHODS: Eight young farm
      pigs were used to develop the technique of applying a laparoscopic Cavitron
      Ultrasonic Surgical Aspirator (CUSA) to the lower esophageal mucosa through an
      operating gastrostomy. A further 11 Yakutan minipigs then underwent CUSA
      epithelial ablation, followed by a laparoscopic Nissen fundoplication or
      postoperative acid suppression therapy. We then assessed the healing response in
      these subjects. RESULTS: Optimal CUSA energy settings enabled complete ablation
      of the squamous epithelium with preservation of the muscularis mucosa and
      submucosa. The integrity of the aspirated cells was sufficient for cytological
      analysis. Healing occurred by squamous regeneration without stricture formation.
      CONCLUSION: The CUSA technique holds promise for complete ablation of the
      Barrett's epithelium in a single setting. The unique tissue-selective nature of
      the ablative process allows complete mucosal reepithelialization without
      stricture formation.

PMID- 9543527
TI  - The effect of peritoneal air exposure on postoperative tumor growth.
AB  - BACKGROUND: Previous work has demonstrated that cell-mediated immune function is
      better preserved in rodents after laparoscopic than open surgery. The cause of
      this laparotomy-related immunosuppression is unclear. Some investigators have
      attributed it to the length of the incision; others, to peritoneal air exposure.
      It has also been shown that tumors in mice are more easily established and grow
      larger after sham laparotomy than after pneumoperitoneum. Lastly, the differences
      in tumor growth have been shown to be, at least in part, attributable to the
      immunosuppression that occurs after laparotomy. The purpose of this study was to
      determine if air pneumoperitoneum, presumably via immunosuppression related to
      peritoneal air exposure, is associated with increased tumor growth in the
      postoperative period. METHOD: A total of 150 immunocompetent syngeneic mice
      received high-dose intradermal injections of mouse mammary carcinoma tumor cells.
      They were then randomized to undergo one of the following procedures: (a)
      anesthesia alone, (b) air insufflation (44 mm Hg), (c) CO2 insufflation, or (d)
      full laparotomy. No intraabdominal procedure was carried out. All procedures were
      20 min long. After 12 days, the animals were killed and the mean tumor mass
      determined for each group. RESULTS: All animals grew tumors. There was no
      significant difference in the mean tumor size of the anesthesia control, CO2
      insufflation, and air insufflation groups (p > 0.85 by ANOVA). However, the
      laparotomy group tumors were 1.5 times as large as those of the other three
      groups (p < 0.05 by ANOVA). CONCLUSIONS: In this model, air insufflation did not
      significantly affect postoperative tumor growth, nor did CO2 pneumoperitoneum.
      However, full laparotomy was associated with increased tumor growth.

PMID- 9543528
TI  - Operative technique for thoracoscopic transmyocardial laser revascularization.
AB  - We describe herein the operative steps used to perform a transmyocardial laser
      revascularization by thoracoscopy. A special technique and specific equipment are
      required for the efficacy and safety of the procedure. Our preliminary results
      with this novel approach suggest that it could be a valid alternative to the
      thoracotomic procedure.

PMID- 9543529
TI  - Endoluminal stenting for benign colonic obstruction.
AB  - We report a case of complete descending colon obstruction due to diverticular
      disease that was initially managed by endoscopic stent placement followed by
      single-stage left colectomy with primary anastomosis. Traditional management of
      complete large bowel obstruction, whether due to benign or malignant disease,
      most often requires a temporary colostomy because of unprepared colon. In this
      case, preparation of the colon was accomplished by successful stenting of the
      benign colonic obstruction. We believe that endoscopic colonic stenting is an
      effective way of avoiding a temporary colostomy in patients with complete large
      bowel obstruction.

PMID- 9543530
TI  - EndoScope: world literature reviews

PMID- 9543531
TI  - J. B. Murphy, M.D. Of buttons and blows.

PMID- 9543533
TI  - Intraoperative screening for common bile duct stonesUltrasound or
      cholangiography?

PMID- 9543532
TI  - SSAT/SAGES minimally invasive surgeryAdvanced laparoscopic hepatobiliary surgery

PMID- 9543535
TI  - Laparoscopic transcystic duct common bile duct exploration

PMID- 9543534
TI  - ERCP interaction with laparoscopic cholecystectomy

PMID- 9543537
TI  - Laparoscopic treatment for right upper quadrant tumors and hepatic metastases

PMID- 9543536
TI  - Laparoscopic choledochotomy for treatment of common bile duct stones

PMID- 9543538
TI  - Endoscopic surgery for pancreaticobiliary cancer

PMID- 9543540
TI  - Integrating advanced laparoscopy into surgical residency training

PMID- 9543539
TI  - Laparoscopic surgery for solid lesions

PMID- 9543541
TI  - SAGES position statement on advanced laparoscopic training

PMID- 9543542
TI  - SAGES statement on concentration in general surgery residency

PMID- 9543543
TI  - Guidelines for granting of privileges for laparoscopic and/or thoracoscopic
      general surgery

PMID- 9543544
TI  - Granting of privileges for gastrointestinal endoscopy by surgeons

PMID- 9543545
TI  - News and notices

PMID- 9543546
TI  - The impact of allergic rhinitis on quality of life and other airway diseases.
      Summary of a European conference.

PMID- 9543547
TI  - Turner syndrome: a cytogenetic and molecular study.
AB  - Two hundred and eleven patients with a clinical diagnosis of Turner syndrome were
      studied. We report (i) the cytogenetic results, (ii) the frequency of cryptic
      mosaicism and (iii) the parental age and the parental origin of the abnormality.
      We scored 100 cells from blood cultures and found 97 patients to have a 45,X
      constitution, 15 to be 45,X/46,XX or 45,X/47,XXX mosaics, 86 to have a
      structurally abnormal X and 13 to have a structurally abnormal Y chromosome.
      Molecular methods were used to look for cryptic X and Y chromosome mosaicism in
      patients with a 45,X constitution. Two cryptic X but no cryptic Y mosaics were
      detected. In 74% of the 45,X patients the X was maternal in origin. The i(Xq)s
      were approximately equally likely to involve the paternal or maternal chromosome,
      while the majority of deletions and rings and virtually all the abnormal Y
      chromosomes were paternal in origin. We suggest that the preponderance of
      paternal errors in Turner syndrome may result from the absence of pairing along
      the greater part of the XY bivalent during paternal mei I, which may make the sex
      chromosomes particularly susceptible to both structural and non-disjunctional
      errors during male gametogenesis.

PMID- 9543548
TI  - Molecular characterization of isochromosomes of Xq.
AB  - We have undertaken a study of 35 patients with i(Xq) to determine whether those
      that are maternally derived originate by similar mechanisms to those that are
      paternally derived. Isochromosome formation is not associated with increased
      parental age and > 90% of i(Xq) contain proximal Xp sequences suggesting that
      centromere misdivision is not a common mechanism of formation. Our results
      indicate that the majority of i(Xq) originate from a single X chromosome and the
      usual mechanisms of formation do not appear to differ according to the parent of
      origin.

PMID- 9543549
TI  - Genetic analysis of a Japanese patient with butyrylcholinesterase deficiency.
AB  - A patient (64-year-old, male) with familial cholinesterasemia caused by BChE
      deficiency was studied. DNA sequence analysis of all exons identified a point
      mutation, an A-->G transition at codon 128, resulting in a Tyr-->Cys
      substitution. The propositus showed extremely low BChE activity, but his other
      family members (three individuals) showed from intermediate to normal BChE
      activity. An immunological method revealed the absence of BChE protein in serum
      of the propositus. Both PCR primer introduced restriction analysis (PCR-PIRA) and
      sequence analysis revealed all three family members to be heterozygotes for this
      mutation.

PMID- 9543550
TI  - Development of a microsatellite-based approach to co-segregation analysis of
      familial hypercholesterolaemic kindreds.
AB  - Co-segregation studies based on a selection of intragenic restriction fragment
      length polymorphisms of the low density lipoprotein receptor (LDLR) gene have
      been used extensively both for research and diagnostic studies of familial
      hypercholesterolaemia (FH) families, because direct mutation screening remains
      complex. Here we describe the development and application of a more efficient
      approach to co-segregation studies based on highly informative dinucleotide and
      tetranucleotide repeats flanking the LDLR gene. A series of microsatellites
      (D19S391, D19S394, D19S221 and D19S179) were selected for study on the basis of
      linkage analysis in the CEPH families using intragenic polymorphisms for a TA
      repeat (exon 18) in the LDLR gene, and earlier data for a Pvu II polymorphism
      (intron 15). A physical map of the region of chromosome 19 also contributed to
      this selection. One marker in particular, D19S394, sited 150 kilobases telomeric
      to the gene, was extremely useful, displaying 90% heterozygosity, robust PCR of
      tetranucleotide repeats without stutter bands, and no recombination with the LDLR
      gene (theta = 0, LOD 68). Use of this marker in the families of twenty-three FH
      probands from Hampshire demonstrated co-segregation of the hyperlipidaemia
      phenotype with the LDLR gene region, except in one family with defective
      apolipoprotein B-100, and a family turning out to display familial combined
      hyperlipidaemia. This approach should facilitate the search for any families
      where FH does not co-segregate with the LDLR gene, and will enhance the
      repertoire of molecular diagnostic tools available for FH.

PMID- 9543551
TI  - A tale of two islands: population history and mitochondrial DNA sequence
      variation of Bioko and Sao Tome, Gulf of Guinea.
AB  - The hypervariable segment I of the control region of the mtDNA was sequenced in
      45 unrelated individuals from Bioko and 50 from Sao Tome, two islands in the Gulf
      of Guinea that have had very different settlement patterns: Bioko was colonized
      around 10000 BP, while Sao Tome was first settled by the Portuguese, who brought
      African slaves to the island. Two different patterns of sequence variation are
      evident and are also clearly a consequence of their very different demographic
      histories. The Bubi present a low genetic diversity and it is likely that the
      island was colonized by a small number of individuals with small later migration.
      Sao Tomeans might be considered a subset of a mainland African population
      relocated to the island. They present high genetic diversity with a high number
      of sequences being shared with many continental populations. This study, with
      knowledge of the population history in island populations, strengthens the
      genetic approach to unravel past demographic events.

PMID- 9543552
TI  - Localization of the fast skeletal muscle troponin I gene (TNNI2) to 11p15.5:
      genes for troponin I and T are organized in pairs.
AB  - We have localized the gene encoding the fast skeletal muscle isoform of troponin
      I (TNNI2) to 11p15.5 by PCR-based analysis of somatic cell hybrid panels: based
      on the Genebridge4 radiation hybrid panel, TNNI2 is coincident with the marker
      D11S922. The gene encoding the fast skeletal muscle troponin T gene (TNNT3) has
      been previously assigned to 11p15.5 suggesting that TNNI2 and TNNT3 may be
      closely linked. The overall location of genes encoding troponin I and T isoforms
      now reveals that they are organized at three loci each containing a troponin
      I/troponin T gene pair. This organization contrasts with all other sarcomeric
      protein genes and has implications for the evolution of these two gene families,
      for their regulation and for the analysis of mutations suspected to result in
      cardiomyopathy.

PMID- 9543553
TI  - DNA polymorphisms of apolipoprotein B in the population of Senegal.
AB  - Three apolipoprotein B (apoB) genetic polymorphisms, the XbaI, MspI and EcoRI
      restriction fragment length polymorphisms (RFLPs), were analysed for 221
      individuals in Senegal by polymerase chain reaction. Allelic frequency
      determination revealed that this population has 0.79 XbaI- (X-), 0.96 MspI+ (M+),
      and 0.89 EcoRI+ (E+). Major genotypes were X-/X- (0.62), M+/M+ (0.92) and E+/E+
      (0.80). The XbaI allele frequency is different (p < 10(-9)) from that in
      Caucasians (0.47) and from that in Mongoloids (0.98). Significant differences
      between Senegalese and Caucasians, and between Senegalese and Mongoloids were
      also observed for the EcoRI and MspI alleles of the apoB genes.

PMID- 9543554
TI  - The role of the hypothalamus-pituitary-adrenocortical and -gonadal axis in
      rheumatoid arthritis.

PMID- 9543555
TI  - Mycobacterium tuberculosis infection in a corticosteroid-treated rheumatic
      disease patient population.
AB  - OBJECTIVE: To investigate the incidence and risk factors of Mycobacterium
      tuberculosis infection in longterm corticosteroid treated rheumatic disease
      patients. METHODS: We assessed retrospectively the incidence of active
      tuberculosis and its risk factors in 269 rheumatic disease patients treated with
      moderate to high doses of corticosteroid for an evaluation period representing
      1,035 corticosteroid years of therapy. RESULTS: The mean daily dose of steroid
      was 18.7 mg prednisolone and the mean daily dose during the first year of
      treatment was 20.4 mg prednisolone. 21 of these patients developed active
      tuberculosis resulting in an incidence rate of 20/1,000 patient-years. Cumulative
      and mean daily steroid doses during the follow-up period and during the first
      year of treatment, and a history of steroid pulse therapy were significantly
      correlated with the development of tuberculosis. A past history of tuberculosis,
      initial chest P-A abnormality, the starting dose of steroid, a history of more
      than 30 mg/day of prednisolone for more than one month, and a history of
      cytotoxic therapy were not related to the development of tuberculosis.
      CONCLUSION: The incidence of active tuberculosis is increased in rheumatic
      patients on moderate-to-high dose steroid treatment. Its risk factors are the
      cumulative and mean daily steroid doses during the follow-up period and during
      the first year of steroid treatment, and a history of steroid pulse therapy.

PMID- 9543556
TI  - Relationship between radiographic classification and arthroscopic findings of
      articular cartilage lesions in osteoarthritis of the knee.
AB  - OBJECTIVE: To examine the relationship between radiographic abnormalities and
      arthroscopic findings of the cartilage lesions in patients with osteoarthritis
      (OA) of the knee. METHODS: Arthroscopy was performed in 190 patients with primary
      medial compartment (MC) OA of the knee to assess the severity of the cartilage
      lesion. Standing radiographs of all patients were graded according to the joint
      space narrowing (JSN) and Kellgren-Lawrence (K/L) scales. In addition to
      evaluating the correlation between arthroscopic articular cartilage lesions and
      the radiographic scale, multiple regression analysis was used to identify the
      arthroscopic findings and clinical factors that influenced the cartilage lesions.
      RESULTS: The positive predictive values of the JSN and K/L scales of the MC for
      the presence of essentially abnormal articular cartilage in the MC by arthroscopy
      were high (0.98, 0.96, respectively). The sensitivity and specificity of the JSN
      scale and the sensitivity and negative predictive value of the K/L scale were
      also high in the MC. In contrast, the positive predictive values of these
      radiographic scales for the presence of arthroscopic lesions in the lateral
      compartment (LC) were poor (0.20 and 0.19). In this study population with severe
      OA, there were more patients with a high K/L score than with a high JSN score in
      the MC. CONCLUSION: In MC-OA of the knee, the JSN and K/L scores for the MC
      correlated highly with cartilage lesions of the MC by arthroscopy. However, the
      cartilage lesion of the LC correlated poorly with both of these radiographic
      scales.

PMID- 9543557
TI  - Prevalence of digital clubbing in bronchogenic carcinoma by a new digital index.
AB  - OBJECTIVE: Clubbing can be a paraneoplastic manifestation of bronchogenic
      carcinoma. We assessed a new digital index of clubbing and used it to determine
      the prevalence of clubbing for different cell types of lung cancer. METHODS:
      Clubbing was assessed by measurement of the thickness of both the base of the
      nailbed (distal phalangeal depth--DPD) and the distal interphalangeal depth (IPD)
      of the index finger in a control group compared to patient groups with either
      chronic obstructive lung disease, or lung cancer. RESULTS: Of the 55 normal
      subjects, no patient had a DPD/IPD ratio of more than 1.05 on either hand, while
      11% of the patients with COPD had a ratio of more than one. For the cancer
      patients, 33% had a ratio greater than one, with 30 of 109 (37%) having a ratio >
      1.05 (chi(2) = 17.6, p < 0.0001). There was no difference in the prevalence of
      clubbing between the 33 squamous cell patients, the 43 adenocarcinoma patients,
      and the 33 small cell lung carcinoma patients included. CONCLUSIONS: Measurement
      of the interphalangeal and distal phalangeal distance demonstrated that one-third
      of patients with lung cancer had evidence of clubbing. The type of bronchogenic
      carcinoma did not appear to affect the proportion of patients with clubbing.

PMID- 9543558
TI  - Soft tissue composition, quadriceps strength, bone quality and bone mass in
      rheumatoid arthritis.
AB  - OBJECTIVES: To examine differences in soft tissue composition, bone quality, bone
      mass and quadriceps strength between women with rheumatoid arthritis (RA) and
      healthy controls. METHODS: 79 women with RA (median disease duration 10 yrs) were
      studied. Most were or had been on steroids. 67 healthy age-matched women served
      as controls. The lean tissue mass (LTM) and fat mass (FM) of the total body and
      of the major body subregions, as well as the bone mineral density (BMD, g/cm2) of
      the femoral neck, spine (L2-L4) and distal forearm were measured by dual energy x
      ray absorptiometry (DXA). Bone quality expressed as the speed of sound (SOS
      m/sec), broadband ultrasound attenuation (BUA, dB/MHz) and stiffness was assessed
      by an Achilles ultrasound device, and isometric quadriceps strength by an
      isokinetic dynamometer. RESULTS: No between-group differences were found for the
      body mass index (BMI, weight/height2), total or regional percentage fat, LTM and
      FM. However, women with RA had 20% lower quadriceps strength than controls. BMD
      at the femoral neck and distal forearm, and SOS, BUA and stiffness were
      significantly lower in patients than in controls. No difference was found for
      spine BMD. In the RA group, z-scores for SOS and stiffness were significantly
      more reduced than those for BMD. Multiple regression analyses indicated negative
      associations between ultrasound parameters and the cumulative steroid dose.
      CONCLUSIONS: Reductions in BMD and muscle strength in RA were not accompanied by
      changes in soft tissue composition, Bone quality assessed by ultrasonography was
      compromised in RA and may be modified by steroids.

PMID- 9543559
TI  - Reconstitution of severe combined immunodeficient mice with spleen cells from
      autoimmune NZBxNZW F1 mice.
AB  - OBJECTIVE: The aim of this study is to establish an animal model to investigate
      the role of individual subsets of immune cells in the pathogenesis of systemic
      lupes erythematosus. METHODS: Spleen cells isolated with from both young and old
      autoimmune NZB/W F1 mice were injected into the peritoneal cavity of severe
      combined immunodeficient (SCID) mice. Sera anti-DNA antibody levels and
      proteinuria of these SCID mice were followed regularly. In addition, histological
      changes of the kidneys were also examined. RESULTS: The data suggest that anti
      ss, dsDNA antibody can be detected in the sera of SCID mice 21 days after
      reconstitution with the spleen cells of either young or old NZB/W F1 mice, with
      titers of antibody increasing over time. In addition, proteinuria was also noted
      in most of these mice 3 months after reconstitution. Histopathological
      examination of the kidney also revealed the typical changes of
      glomerulonephritis. Immunofluorescence staining of kidney sections also
      demonstrated immune complex deposition. CONCLUSION: Once validated, this animal
      model could be used in future studies to investigate the role of individual
      subsets of cells in the pathogenic mechanisms of SLE.

PMID- 9543560
TI  - Actinically degenerate elastic tissue: the prime antigen in the giant cell
      (temporal) arteritis syndrome? New data from the posterior ciliary arteries.
AB  - OBJECTIVE: To search for evidence of actinic elastotic degeneration (actinic
      arteriopathy) and giant cell arteritis (GCA) in the posterior ciliary arteries of
      eyes from aged white Australians. METHODS: Three hundred donor eyes were given to
      us by the Lions Eye Bank of New South Wales at Sydney Hospital. Of these, 146
      formed the basis of this study. Portions of the posterior ciliary arteries
      located in relation to the optic nerve heads were processed in paraffin and were
      then stained by a sensitive haematoxylin and eosin stain that had been especially
      developed to display actinic elastotic degeneration of elastic tissue. RESULTS:
      Among 60 "aged" subjects (70-90 yrs.), a total of 41 (approximately 68%) showed
      definite changes of actinic elastotic degeneration in their laminae, a condition
      called actinic arteriopathy. One of these subjects revealed giant cells on
      degenerate lamina, giving a picture regarded as early (pre-clinical) GCA. A young
      "control" group of 60 subjects 17-59 years of age revealed only one subject with
      a similar degree of actinic arteriopathy. CONCLUSIONS: Actinic arteriopathy of
      the posterior ciliary arteries was more frequent and advanced in the "aged", over
      70 group as compared with changes in the "young" group < 60 years of age. One
      aged subject without a history of eye disease showed giant cells associated with
      elastotically degenerate internal elastic lamina. Her fortuitous lesions are
      regarded as indicative of how GCA is likely to begin in the damaged arteries.

PMID- 9543561
TI  - Quality of life assessment during six months of NSAID treatment [Gonarthrosis and
      Quality of Life (GOAL) Study].
AB  - OBJECTIVE: To identify the time point of the greatest degree of improvement in
      daily living activities, pain and depression in patients with osteoarthritis (OA)
      of the knee during 6 months of treatment with NSAIDs, in order to define
      compliance and drop-out rate. METHODS: 107 patients were recruited into a
      multicentre, prospective, randomized, controlled trial comparing two treatments,
      piroxicam-beta-cyclodextrin (PBCD) and slow release diclofenac (DCL). RESULTS:
      The greatest improvement in quality of life occurred in both groups after 3
      months, with a slight further gain observed by the end of treatment. The Stanford
      Health Assessment Questionnaire score improved (p < 0.05 vs baseline) at 3 and 6
      months with PBCD and at 6 months with DCL. The Arthritis Impact Measurement Scale
      score improved (p < 0.05 vs baseline) after 6 months in both groups. Significant
      (p < 0.05 vs baseline) improvement in other psychological and pain scores were
      recorded in both groups after 3 and 6 months. Compliance with treatment at 3
      months was 73% for PBCD and 72% for DCL, and was 60% in both groups at 6 months.
      CONCLUSIONS: The results of this study indicate that the optimal length of time
      for an NSAID trial in OA patients is 3 months, when assessment of daily living
      activities is considered as the main outcome criterion.

PMID- 9543562
TI  - C4A and C4B null alleles are genetic markers of different types of systemic
      sclerosis in Japanese patients.
AB  - OBJECTIVE: The contribution of the polymorphism of complement C4A and C4B alleles
      to the pathogenesis of systemic sclerosis (SSc) was studied in Japanese patients.
      METHODS: C4A and C4B typing was carried out in 44 SSc patients and in 83 normal
      subjects using electrophoresis followed by immunofixation and immunoblotting. HLA
      DR typing and HLA DRB1*15 and *08 genotyping were carried out by the PCR method
      and the PCR-SSCP method, respectively. RESULTS: In SSc with diffuse scleroderma,
      the frequency of C4BQ0 was significantly increased (44.4%, p < 0.001, pc < 0.01).
      In SSc with antitopoisomerase I antibody (a-Scl-70) C4BQ0 was also increased
      (50.0%, p < 0.001, pc < 0.01). Association analysis indicated that the increase
      in C4BQ0 was not primary but reflected an increase in HLA-DRB1*1502. In contrast,
      C4A/Q0 was significantly increased in limited scleroderma (53.8%, p < 0.005, pc <
      0.05) and SSc without a-SCL-70 (53.8%, p < 0.005, pc < 0.05). CONCLUSION: Diffuse
      scleroderma with SSC with a-Scl-70 have different genetical backgrounds from
      limited scleroderma and SSc without a-Scl-70, respectively, in Japanese patients.
      C4AQ0 were independent genetic markers for each clinical subgroup and for a a-Scl
      70 positivity.

PMID- 9543563
TI  - The management of osteoporosis-related fractures: a survey of orthopaedic
      surgeons' practice.
AB  - A questionnaire survey of 70 orthopaedic surgeons regarding their policy for the
      management of osteoporosis-related fractures revealed that, in the main, UK
      Department of Health guidelines on osteoporosis are not followed uniformly,
      although Royal College of Physicians guidelines regarding rehabilitation are met
      more frequently. A written policy or agreed protocol with an osteoporosis service
      may potentially benefit a large number of patients and reduce future fracture
      risks.

PMID- 9543564
TI  - Association of mast cells with fibrosis and fatty infiltration in the minor
      salivary glands of patients with Sjogren's syndrome.
AB  - OBJECTIVE: To determine the distribution and density of mast cells in the minor
      salivary glands of patients with primary Sjogren's syndrome (pSS) and of normal
      controls. METHODS: Minor salivary gland biopsies were obtained from 19 patients
      with pSS, 9 with systemic lupus erythematosus, one each with rheumatoid
      arthritis, sarcoidosis, and Hodgkin's disease, and from 10 individuals who had
      subjective xerostomia with normal salivary gland biopsies. Biopsy specimens were
      evaluated for the degree of inflammation according to Tarpley's classification.
      Sections were analysed for staining with Toluidine blue and with the mast cell
      specific marker c-kit. The data obtained were correlated with the histological
      findings of fatty infiltration, fibrosis and lymphocytic infiltration. RESULTS:
      There was a significant correlation between the number of mast cells identified
      and the degrees of fibrosis and fatty infiltrates. There was no correlation
      between the intensity of lymphoid infiltration and the number of mast cells. c
      kit staining showed a high correlation when compared to Toluidine blue staining.
      CONCLUSION: Mast cells in the minor salivary glands of patients with pSS are
      strongly associated with fibrosis and cell acid infiltration. However, there is
      no correlation with parameters of disease activity such as lymphoid infiltration.

PMID- 9543565
TI  - HLA-TNF haplotype heterogeneity in Greek SLE patients.
AB  - OBJECTIVE: To examine TNF microsatellite allele frequencies in SLE patients in
      the Greek population, where disease susceptibility is less associated with HLA
      DR3 haplotypes. METHODS: A cohort of 46 Greek SLE patients were investigated.
      Allele frequencies for the TNF microsatellite markers a, b, c and d were
      determined using a fluorescence based DNA fragment sizing technique. HLA class II
      typing was performed using a molecular based technique. RESULTS: Associations
      between SLE and DRB1*1501, *1601 and *0701 were observed and DRB1*0301 was only
      marginally increased in patients. Linkage disequilibrium was found between
      DRB1*1501 and TNF a11 and also for DR3 and TNF a2, b3, d2. Stratification of
      patients suggested that DRB*1501 and TNF a11 frequencies were higher in SLE
      patients with renal disease and TNF a2 and b 3 frequencies in those without,
      although these differences did not reach statistical significance. CONCLUSIONS:
      SLE in this Greek population appears to be associated with a number of HLA-DRB1
      alleles. The development of renal complications in these patients may be related
      to the TNF polymorphism encoded on these HLA haplotypes.

PMID- 9543566
TI  - Sucrose permeability as a marker for NSAID-induced gastroduodenal injury.
AB  - OBJECTIVE: To evaluate sucrose permeability as a non-invasive test for the
      monitoring of upper gastrointestinal mucosal damage (uGMD) in patients treated
      with NSAIDs. METHODS: 40 patients with non-inflammatory joint pain were enrolled
      in a prospective study. Before and after 14 days of ibuprofen treatment (3 x 400
      mg/day), the rates of urinary sucrose excretion after an oral sucrose load were
      assessed. Individuals with increased sucrose permeability underwent endoscopy.
      RESULTS: 8 patients (20%) showed abnormal sucrose permeability before taking any
      NSAID. In 5/20 patients (25%) who completed 2 weeks of ibuprofen medication,
      sucrose excretion increased above the normal level. Endoscopic examination and
      biopsy revealed mild uGMD, but no ulceration in 8/11 (72%) patients with
      increased permeability to this marker. CONCLUSION: Sucrose permeability testing
      is a sensitive procedure for research protocols on NSAID-induced gastropathy.
      Since this test also seems to detect slight and clinically insignificant mucosal
      damage, however, its use in clinical decision-making regarding gastroprotective
      medication is limited.

PMID- 9543567
TI  - Fever and abdominal pain in a 45-year-old woman with cutaneous necrotising
      vasculitis.

PMID- 9543568
TI  - Selective IgA deficiency with recurrent vasculitis of the central nervous system.
AB  - We describe an unusual case of selective IgA deficiency complicated by recurrent
      vasculitis of the central nervous system (CNS). The patient suffered from two
      episodes of CNS vasculitis, one of which was located in the cerebrum and the
      other in the cerebellum. The vasculitic process resulted in brain tumor-like
      lesions shown by computed tomography. There was no evidence of associated
      connective tissue diseases. Vasculitis in other organs or tissues was not noted.
      This is the first detailed description in the English literature of
      pathologically proven CNS vasculitis in a patient with selective IgA deficiency.
      Our report demonstrates that isolated CNS angiitis can be a rare clinical feature
      of selective IgA deficiency.

PMID- 9543569
TI  - Hepatic hypertrophic osteoarthropathy: the value of liver transplantation.
AB  - We describe 4 cases of hepatic hypertrophic osteoarthropathy treated successfully
      by liver transplantation. Hepatic hypertrophic osteoarthropathy is a rare and
      disabling condition associated with severe liver diseases. It responds poorly to
      conservative management, and liver transplantation is the only radical treatment
      option.

PMID- 9543570
TI  - Acquired winged scapula in a patient with systemic lupus erythematosus.
AB  - A 34-year-old woman presented with a right winged scapula 8 months after
      developing systemic lupus erythematosus (SLE) with subacute cutaneous
      manifestations. The patient experienced severe shoulder pain followed by weakness
      of the right arm in the typically winged scapula fashion. Electromyography of the
      serratus anterior showed long thoracic nerve palsy. Clinical and laboratory signs
      did not reveal any associated disease. Paralysis of the long thoracic nerve has
      never been described before in SLE.

PMID- 9543572
TI  - Reclassifying the pathogenesis of rheumatoid arthritis: from the susceptibility
      to the degenerative stages.
AB  - Rheumatoid arthritis is a heterogeneous disease in which different pathogenic
      mechanisms have been suggested. Recent advances in immunology and immunogenetics
      have contributed to a better understanding of this complex illness. Several
      stages have been previously described, based on clinical and radiological
      findings, and proposing different therapeutic options. We have analysed previous
      classification schema, making some changes and incorporating new knowledge. Our
      classification system includes a susceptibility stage and a degenerative stage.
      Therapeutic options are described for each stage. We hope that this will provide
      useful guidelines in the future for clinicians and researchers.

PMID- 9543571
TI  - Non-X-linked hyper-IgM syndrome with systemic lupus erythematosus.
AB  - A 24-year-old woman had suffered from recurrent bacterial infections and clinical
      manifestations of systemic lupus erythematosus (SLE). Laboratory findings
      disclosed an elevated level of serum IgM, markedly decreased IgG, IgA, IgD and
      IgE levels, and low levels of serum complement. Both the CD40 and CD40 ligands
      appeared to be normally expressed. Assays of in vitro immunoglobulin production
      by lymphocytes showed that IgM was produced normally and that IgE but not IgG or
      IgA production was rescued by signaling through CD40 on B cells. The
      proliferative response of lymphocytes to phobol ester was markedly decreased,
      suggesting some impairment of signal transduction in the patient's lymphocytes.

PMID- 9543573
TI  - Association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis
      in a child.
AB  - The authors report the case of a 15-year-old, HLA-B27-positive male patient who
      presented a rare association of ankylosing spondylitis, Crohn's disease and
      Takayasu's arteritis, which resulted in death. A brief review of the literature
      is provided.

PMID- 9543574
TI  - Thrombomodulin, tissue plasminogen activator and plasminogen activator inhibitor
      1 in Henoch-Schonlein purpura.
AB  - OBJECTIVE: To evaluate the changes in the plasma levels of thrombomodulin (TM),
      tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1
      (PA1-1) as indices of endothelial injury/activation and fibrinolysis in childhood
      Henoch-Schonlein purpura (HSP). METHODS: Twenty-six children with HSP aged
      between 4-15 years and 10 healthy controls were included in the study. Blood
      samples were taken from these patients at admission and 6-12 weeks after healing
      of skin rash and arthritis. Plasma levels of TM, t-PA and PAI-1 activities and t
      PA and PAI-1 antigen (Ag) levels were measured. RESULTS: The plasma levels of TM,
      t-PA Ag and PAI-1 Ag in patients during the acute phase were significantly
      different from the controls. The difference in TM between the acute phase and
      recovery in patients was also significant. The decrease in plasma levels of t-PA
      Ag and PAI-1 Ag in patients between the acute and recovery phases was not
      significant. t-PA activity was significantly higher in the acute phase than in
      the recovery phase. CONCLUSION: We suggest that increased levels of TM, t-PA, and
      PAI-1 activity may reflect the presence of endothelial injury and/or activation
      and fibrinolytic activation in patients with HSP.

PMID- 9543575
TI  - Epidemiology of juvenile chronic arthritis in northern Norway: a ten-year
      retrospective study.
AB  - OBJECTIVE: To study the incidence and prevalence of juvenile chronic arthritis
      (JCA) in northern Norway. METHODS: Cases from the period 1985-1994 were
      retrospectively identified from the hospital files of the only pediatric
      department treating JCA in the study area. The European League Against Rheumatism
      (EULAR) criteria for JCA were used. RESULTS: The annual incidence of JCA was
      22.6/100,000 children under 16 years of age. The incidence of oligoarticular JCA
      was 11.8, and the incidence of systemic JCA was 0.8/100,000. In the incidence
      group 25% were ANA positive, 14% developed uveitis and 42% of the tested patients
      were HLA-B27 positive. The point prevalence was 148.1/100,000. CONCLUSION: These
      incidence and prevalence data are higher than those reported in most other
      studies. The impact of genetic differences, cyclic variations and other factors
      in relation to the onset and course of JCA merit further investigation.

PMID- 9543576
TI  - Atypical renal onset and involvement in primary antiphospholipid syndrome in a
      child.
AB  - A case of primary antiphospholipid syndrome (APS) with renal involvement in a 10
      year-old child is reported. The peculiarity of the case resided not only in the
      apparent "primary" occurrence of APS in the pediatric age, but also in the
      involvement of the kidney. The renal picture in the case described consisted of a
      focal proliferative glomerulonephritis, without any sign of glomerular
      thrombosis. We conclude that this should lead to a consideration of primary APS
      in the differential diagnosis of nephropathies, also in childhood.

PMID- 9543577
TI  - Severe anemia due to hemorrhagic gastritis associated with Sjogren's syndrome.

PMID- 9543578
TI  - Evaluation of S-adenosylmethionine in secondary fibromyalgia: a double-blind
      study.

PMID- 9543579
TI  - Simultaneous development of SLE-like syndrome and autoimmune thyroiditis
      following alpha-interferon treatment.

PMID- 9543580
TI  - CD11b positive blood lymphocytes correlate with disease activity in patients with
      RA.

PMID- 9543581
TI  - Beneficial effect of a thiazide diuretic on bone mineral density in male
      osteoporosis with hypercalciuria.

PMID- 9543582
TI  - Magnetic resonance imaging findings in acute cerebellitis.
AB  - Cerebellitis, also known as acute cerebellar ataxia, is an inflammatory syndrome
      of cerebellar dysfunction that may reflect an infectious, post-infectious, or
      post-vaccination disorder. We present serial magnetic resonance imaging (MRI)
      findings in a partially reversible, idiopathic cerebellitis. Bilateral cerebellar
      parenchymal abnormalities were noted, including hyperintensities on T2-weighted
      images and cerebellar swelling. After contrast administration, the cerebellum
      showed abnormal bilateral enhancement. The authors state this represents the
      first report of abnormal contrast enhancement in this condition. The MRI lesions
      most likely reflect the reversible, inflammatory nature of the syndrome.

PMID- 9543583
TI  - Power Doppler findings in nasopharingeal angiofibroma.
AB  - Juvenile nasopharingeal angiofibroma (JNA) is a rare, histologically benign but
      clinically malign hypervascular tumor localized in the nasopharynx which occurs
      exclusively in adolescent boys. There is no definite attitude towards etiology of
      angiofibroma. In diagnostics, besides epypharyngoscopy, computed tomography and
      magnetic resonance imaging are the primary diagnostic tests. Angiography is used
      for preoperative embolization. In this case report, we aim to demonstrate the
      vascularity of JNA with power Doppler sonography (PDS) and advanced vasculature
      was observed into tumoral lesion with PDS.

PMID- 9543584
TI  - Evaluation of galactography for nipple discharge.
AB  - Galactography is useful in the evaluation of spontaneous discharge from the
      nipple of a nonlactating breast. Without galactography, surgeons have relied on
      either masectomy or excision of the major duct system responsible for the
      discharge. From January 1989 to May 1996, 106 galactograms were performed with
      monofilament polypropylene suture guiding for duct cannulation in 105 cases. The
      discharge duct was identified by pre-operative galactography, followed by a
      selective excision of ductal-lobular unit. In all tissue specimens, the cause of
      the pathologic secretion was found histologically; most often, it was intraductal
      papilloma (42.6%). In 35.6% of the specimens, findings with a prospective
      significance (papillomatosis, hyperplasia, carcinoma) were discovered and further
      operative treatment was initiated. The color of the discharge allowed no
      prediction of the histological findings. The accuracy of galactography was 88.4%,
      84.6%, and 77.4% in papilloma, cancer, and other benign lesions, respectively. It
      is better than physical examination and other tests. Galactography represents a
      useful test in the diagnostic workup of secretory breasts.

PMID- 9543585
TI  - Tamoxifen-induced regression of breast cysts.
AB  - The use of Tamoxifen as treatment for breast cancer is well established and its
      use experimentally as prophylaxis is promising, but little has been written about
      mammographically detected changes in breast parenchyma as a result of Tamoxifen
      therapy. We report two cases of spontaneous regression of breast cysts after
      Tamoxifen therapy for premenopausal breast cancer in the contralateral breast.

PMID- 9543586
TI  - Wegener's granulomatosis upper respiratory tract and pulmonary radiographic
      manifestations in 30 cases with pathogenetic consideration.
AB  - Although the radiographic manifestations and pathologic features of Wegener's
      granulomatosis have been well described, their relationship to two variants of
      anti-neutrophil cytoplasmic antibodies (c- and p-ANCA) remains unclear. The
      purposes of this study are to analyze the radiographic and pathologic findings in
      30 patients with Wegener's granulomatosis and to correlate c- and p-ANCA with
      such findings. Major histologic findings included parenchymal necrosis,
      necrotizing vasculitis, and granulomatous inflammations. Nodular lesions were
      more often associated with arteritis whereas patchy fluffy lesions associated
      with hemorrhagic capillaritis. ANCAs, particularly c-ANCA, instead of p-ANCA,
      were present in a high percentage of patients tested. These findings suggest that
      c-ANCA could play an important pathogenetic role in Wegener's granulomatosis
      which showed dual pathologic processes: vasculitis and granulomatous inflammation
      manifested radiographically as either nodular or pneumonia-like lesions, whereas
      p-ANCA was more often associated with patchy fluffy lung lesions as the
      consequence of hemorrhagic capillaritis.

PMID- 9543587
TI  - Pancreaticopleural fistula. An unusual cause of persistent unilateral pleural
      effusion.
AB  - There are a myriad of causes of a large persistent pleural effusion.
      Pancreaticopleural fistula is a rare entity seldomly included in the above
      differential. As it usually presents with thoracic rather than abdominal
      symptoms, a combination of imaging modalities, including chest radiography (CXR),
      computerized tomography (CT) and endoscopic retrograde cholangiopancreatography
      (ERCP) is essential in obtaining the diagnosis.

PMID- 9543588
TI  - Spiral CT with 3D reconstruction in children requiring reoperation for failure of
      chest wall growth after pectus excavatum surgery. Preliminary observations.
AB  - Pectus excavatum is the most common congenital chest wall deformity. Extensive
      corrective surgery prior to age 3 may disturb chest wall growth and result in a
      constricted thorax. We describe our surgical and radiologic experience with eight
      such cases, paying particular attention to the role of spiral computed tomography
      (CT) with 3D reconstruction in patient management. Spiral CT was performed on
      children who had developed restrictive chest walls following pectus excavatum
      surgery. These children then underwent a unique operation to elevate the sternum
      and attempt to correct their restrictive chest wall defects. In several cases,
      postoperative spiral CT was performed. Spiral CT with 3D reconstruction defined
      the orientation of the ribs and costal cartilages and their relationship to the
      sternum, allowing exact preoperative measurement of the bony rib cage and guiding
      individualized operative correction. Computed thoracic volumes in select cases
      correlated well with subjective patient reports of increased exercise capacity.
      Repair of pectus excavatum defects prior to age 3 may result in constrictive
      thoracic abnormalities. Surgical correction can increase thoracic volume and
      improve prospects for normal thoracic function. Three-dimensional reconstruction
      of spiral CT data is useful in both preoperative and postoperative evaluation.

PMID- 9543589
TI  - Arterio-esophageal communication from a ruptured aberrant right subclavian artery
      aneurysm. CT diagnosis.
AB  - We report the computed tomography (CT) findings of an arterio-esophageal
      communication from an aberrant right subclavian artery aneurysm which had eroded
      into the esophagus. Pathologic correlation is provided. To our knowledge, this is
      the first CT demonstration of an aberrant right subclavian aneurysm causing a
      communication to the esophagus reported in the literature. Previously, one CT
      case of a left aberrant subclavian artery aneurysm that had ruptured into the
      esophagus, had been described. The characteristic location of the aberrant vessel
      with aneurysmal dilation and the presence of abnormal air identified within the
      wall of the aneurysm on CT, helped establish the diagnosis antemortem.

PMID- 9543590
TI  - CT demonstration of infected SVC thrombus.
AB  - We report a case in which computed tomography (CT) demonstrated gas within a
      thrombus in the superior vena cava in a patient with fever of unknown origin
      (FUO), indicating that the thrombus was infected. This CT finding is important to
      recognize, as it affects subsequent therapy.

PMID- 9543591
TI  - Castleman disease mimicking a hepatic neoplasm.
AB  - Castleman disease, or angiofollicullar hyperplasia, is a rare cause of lymph node
      enlargement. This most commonly occurs within the thorax, although rare
      extrathoracic presentations have been described. Only two cases with hepatic
      localization have been reported. We present a case of Castleman disease within
      the porta hepatis masquerading as a hepatic neoplasm.

PMID- 9543592
TI  - MRI findings in adenosquamous carcinoma of the gallbladder.
AB  - In this report, we present the MRI findings of adenosquamous carcinoma of the
      gallbladder, a rare type of gallbladder malignancy. MRI examination not only
      helped established the diagnosis but also accurately depicted the extent of
      involvement of the adjacent liver. The ability to image in multiple planes was
      also useful in assessing the anatomic location of the tumor and in determining
      that the patient could be treated with surgical resection.

PMID- 9543593
TI  - Cardiac-triggered and segmented two-dimensional MR angiography of peripheral
      arterial occlusive disease. A pictorial essay.
AB  - Magnetic resonance (MR) angiography has been shown to be an important technique
      to image the vasculature of the lower extremities. The two-dimensional (2D) time
      of-flight technique has evolved as the standard method of MR angiography used to
      examine patients with peripheral arterial occlusive disease (PAOD). There is
      evidence that cardiac triggering substantially improves the quality of 2D time-of
      flight angiography. In this pictorial essay, we describe PAOD, show the results
      of this nonintrusive angiographic technique, and provide a current overview of
      the interventional and surgical management of PAOD.

PMID- 9543594
TI  - Membranoproliferative glomerulonephritis in the aged and its possible causal
      relationship with CD8+CD57+ lymphocytes.
AB  - Membranoproliferative glomerulonephritis (MPGN) is a chronic progressive
      glomerulonephritis that occurs primarily in patients under the age of 30, and is
      rare in the elderly. We report eight aged patients with MPGN associated with
      CD8+CD57+ lymphocytosis. All eight patients showed a significant increase in
      CD8+CD57+ lymphocytes with a significant decrease in the ratio of CD4+ cells to
      CD8+ cells. Infiltration of CD8+CD57+ lymphocytes was observed within capillary
      lumens to various degrees according to the severity of endocapillary
      proliferation in each case. Expression of endothelial-leukocyte adhesion molecule
      1 was observed in a focal and segmental manner on glomerular endothelial cells
      and on the endothelium of arterioles and arteries in kidney tissue in four cases
      in which a pronounced endocapillary proliferation was simultaneously seen. These
      findings suggest that cell-mediated cytotoxic mechanisms against glomerular
      endothelial cells may be involved in the pathogenesis of MPGN in the aged.

PMID- 9543595
TI  - Glomerular enlargement in the progression of mesangial proliferative
      glomerulonephritis.
AB  - A close association between glomerular hypertrophy and subsequent sclerosis had
      been demonstrated in diverse animal and human studies. We investigated the
      relationship between the glomerular volume and glomerular constituents (mesangial
      matrix, mesangial cells and capillary lumens) in human mesangial proliferative
      glomerulonephritis (GN). The data were obtained from glomeruli in the specimens
      of 23 patients undergoing repeat renal biopsies. Glomerular volume and glomerular
      constituents of each patient were obtained by averaging those of all glomeruli in
      each specimen. The interval from the first biopsy to the second was 51.2 +/- 6.8
      months and the number of glomeruli included in each specimen was 16 +/- 1.
      Between glomerular volume and fractional mesangial volume, three patterns were
      recognized. In 8 of 23 patients glomerular volume and fractional mesangial volume
      were increased in the second biopsy (Group A). In 12 of 23 patients glomerular
      volume was decreased and fractional mesangial volume increased in the second
      biopsy (Group B), and in 3 of 23 patients glomerular volume was increased and
      fractional mesangial volume decreased in the second biopsy (Group C). One patient
      who underwent renal biopsy three times shifted from Group A to Group B in the
      course of mesangial proliferative GN. At the final follow-up, 4 of 12 patients in
      Group B required hemodialysis in contrast to none of 8 patients in Group A.
      Between glomerular volume and fractional mesangial volume, a positive and inverse
      relation existed, and we considered that in the course of mesangial proliferative
      GN, initially, glomerular size increases and thereafter decreases progressively.
      With glomerular enlargement, mesangial matrix expansion, glomerular capillary
      enlargement and relative decrease of the number of capillary lumen profiles and
      mesangial cells per glomerulus to increased glomerular volume were recognized. We
      concluded that these histological changes play a role in the progression of
      mesangial proliferative GN in humans as has been speculated in animal models of
      renal ablation.

PMID- 9543596
TI  - Inadequate suppression of angiotensin II modulates left ventricular structure in
      humans.
AB  - BACKGROUND: In a previous study we found that high angiotensin II levels in
      relation to the corresponding urinary sodium excretion aggravate left ventricular
      hypertrophy in hypertensive patients. To analyze whether a dysregulation of the
      renin angiotensin aldosterone system determines left ventricular structure in
      young individuals, we examined whether the response of angiotensin II after
      increasing salt intake is related to left ventricular structure. METHODS: In 51
      young, male Caucasians with normal or mildly elevated blood pressure, left
      ventricular structure, 24-hour ambulatory blood pressure and dietary sodium
      intake (as estimated by 24-hour sodium excretion) were determined in parallel
      with plasma renin activity, angiotensin II, and aldosterone concentrations.
      Angiotensin II concentration and 24-hour sodium excretion were measured twice:
      firstly on a normal Bavarian diet and secondly at high salt intake to determine
      the resulting suppression of the renin-angiotensin-aldosterone system. RESULTS:
      Body mass index (r = 0.42, p < 0.001) and both systolic (r = 0.28, p < 0.05) and
      diastolic (r = 0.25, p < 0.05) 24-hour ambulatory blood pressure correlated with
      left ventricular mass. No direct relationship was found between left ventricular
      structure and baseline angiotensin II concentration. The lower the physiological
      decrease of angiotensin II after high oral salt intake, i.e. the higher the
      angiotensin II level after salt intake remained, the greater was left ventricular
      mass (r = 0.38; p < 0.006) even after taking 24-hour ambulatory blood pressure
      into account (partial correlation; r = 0.43, p < 0.005). Consistently,
      angiotensin II concentration at high salt intake correlated with left ventricular
      mass independently of ambulatory blood pressure (partial correlation: r = 0.29, p
      < 0.05). Subgroup analysis revealed that the increase in sodium excretion at high
      salt intake was related to the decrease in angiotensin II levels in normotensive
      (r = -0.43, p < 0.05), but not in hypertensive subjects (r = 0.16, n.s.). The
      changes in angiotensin II concentration at high salt intake were related to left
      ventricular mass in hypertensive (r = 0.43, p < 0.02), but not in normotensive
      individuals (r = 0.21, n.s.). CONCLUSION: Our finding that angiotensin II
      concentration at high salt intake correlated with left ventricular mass
      independently of ambulatory blood pressure suggests that inadequate suppression
      of angiotensin II after high salt intake contributes to left ventricular
      hypertrophy already in young hypertensive individuals independently of blood
      pressure.

PMID- 9543597
TI  - A comparison of the safety and efficacy of mibefradil and nifedipine SR in
      patients with renal disease and hypertension.
AB  - The antihypertensive efficacy and safety of mibefradil and nifedipine SR were
      compared in 143 patients with chronic renal failure and mild-to-moderate
      hypertension in a multicenter, double-blind, randomized, parallel-design study.
      At treatment week 12, a significantly greater decrease in sitting diastolic blood
      pressure (SDBP) was seen with mibefradil than with nifedipine SR (12.8 mmHg vs
      8.1 mmHg, respectively; p = 0.014). A significantly greater number of mibefradil
      treated patients achieved normalization of SDBP by week 12 (62% vs 37%; p <
      0.01). The changes in renal function parameters and the incidence of adverse
      events were similar in both groups. In this population, 12 weeks of treatment
      with mibefradil were more effective than nifedipine SR for lowering blood
      pressure and had similar effects on renal function parameters.

PMID- 9543598
TI  - Contribution of tubular anion and cation secretion to residual renal function in
      chronic dialysis patients.
AB  - The clearance of organic ions by the tubules may contribute to the removal of
      uremic waste products in dialysis patients. The renal excretion of an exogenous
      anion p-aminohippurate (PAH) was investigated in 10 peritoneal dialysis patients
      and 10 hemodialysis patients during one clearance period and compared with the
      clearance of creatinine (Ccr) and inulin (CIn). The clearance period was 24 hours
      in the peritoneal dialysis patients and one interdialytic interval of 3 days
      divided in 4 parts [CPA-D] in hemodialysis patients. In peritoneal dialysis
      patients the renal clearance of total PAH (median 14.3 ml/min, range 3.8-33.0)
      exceeded the CIN (median 3.2 ml/min, range 1.6-11.2, p < 0.005) and Ccr (median
      4.0 ml/min, range 1.7-15.0, p < 0.005). A positive correlation was found between
      the tubular clearances of creatinine (cationic pathway) and of total PAH (anionic
      pathway, r: 0.72, p <0.02). In hemodialysis patients the clearance of total PAH
      (CPA: median 2.0, range 0.8-9.6; CPD: median 3.8, range 1.7-15.4) also exceeded
      the clearance of inulin (CPA: median 1.5, range 0.2-3.4; CPD: median 2.7, range
      0.9-4.4) in the beginning and the end of the interdialytic interval (p < 0.005).
      The CIN and the clearance of total PAH increased during the interdialytic
      interval, but the Ccr (CPA: median 2.2, range 0.4-8.9, CPD: median 2.9, range 1.2
      4.6) remained stable. Thus, the change in tubular clearance of creatinine and PAH
      was opposite during the interdialytic interval: it increased for total PAH and
      decreased for creatinine. The CTPAH/CIN ratio in hemodialysis patients was lower
      than in peritoneal dialysis patients. In CPA it was median 1.6 (range 1.1-5.6, p
      < 0.05) and in CPD it was median 1.7 (range 1.1-5.0, p < 0.02) and in the
      peritoneal dialysis patients it was median 3.6 (range 1.5-9.1). We conclude that
      tubular clearances contribute to the residual renal function in dialysis
      patients, but the tubular handling of anions and cations in relation to the
      residual GFR is different between peritoneal and hemodialysis patients. A
      difference in clearance of organic acids caused by the dialysis techniques may be
      an explanation for the differences in clinical outcome between the two dialysis
      modalities.

PMID- 9543599
TI  - Assessment of PD treatment delivered by 125I-Iothalamate plasma disappearance.
AB  - The calculation of treatment delivered to PD patients requires the collection of
      PD effluent, plasma and urine samples. 125I-Iothalamate plasma disappearance,
      which eliminates the need for PD effluent collections, was tested as an alternate
      method to measure the weekly PD treatment delivered. Two protocols were designed.
      In protocol A, a 35 microCi dose of 125I-Iothalamate was injected in three
      subjects and allowed to equilibrate. A plasma sample was taken and patients
      returned on both of the following two days with timed labeled effluent bags and a
      24-hour urine collection for each day. The timed PD effluent and 24-hour urine
      collections were measured for 125I-Iothalamate, urea and creatinine
      concentrations. 125I-Iothalamate and urea clearances were strongly correlated for
      both PD (R2 = 0.76, n = 24) and renal (R2 = 0.92, n = 6) clearances. In protocol
      B, thirteen subjects were given a 35 microCi injection of 125I-Iothalamate. A
      blood sample was taken one hour post injection and a second blood sample taken on
      day five. Kt/V were calculated from the 125I-Iothalamate plasma disappearance
      curve and compared to weekly Kt/V values extrapolated from one day's collections
      (Traditional Method). The comparison of Kt/V values found by 125I-Iothalamate
      Method vs. the "Traditional Method" yielded R2 = 0.79, n = 13. In conclusion, the
      plasma disappearance of 125I-Iothalamate is an alternate method of determining
      weekly Kt/V, over an extended period of time, which eliminates the need for PD
      effluent collections.

PMID- 9543600
TI  - Four-site skinfold anthropometry (FSA) versus body impedance analysis (BIA) in
      assessing nutritional status of patients on maintenance hemodialysis: which
      method is to be preferred in routine patient care?
AB  - BACKGROUND: Both four-site skinfold anthropometry (FSA) and bioelectrical
      impedance analysis (BIA) claim to be useful in routine clinical practice of
      maintenance dialysis as easy methods to assess nutritional status. The purpose of
      this study was to investigate which of these two methods is to be preferred.
      METHODS: Both before and after dialysis nutritional and hydration status were
      evaluated by BIA in 20 stable hemodialysis patients. Variables of nutritional
      status as lean body mass (LBM) and body fat (BF) were assessed by four-site
      skinfold anthropometry (LBM-FSA and BF-FSA) and BIA (LBM-BIA and BF-BIA).
      Variables of hydration status were total body water (TBW), its distribution into
      intracellular and extracellular compartments (ICW and ECW, respectively) and
      ICW/ECW. RESULTS: Weight loss during dialysis correlated with a change of LBM-FSA
      (r = 0.75, p <0.005) and also with that of LBM-BIA (r = 0.69, p < 0.005). To
      promote reliability of follow-up measurements in intervention studies it is
      warranted to evaluate nutritional status in an unchanged hydration status. The
      highly significant correlation (r = 0.93, p < 0.005) between the two techniques
      and the comparability between means and SD indicate that both techniques were
      almost equivalent to each other, although, compared to LBM-BIA, LBM-FSA was less
      affected by changes in fluid status. The sam held true for BF-BIA and BF-FSA. BF
      FSA correlated significantly with BF-BIA (r = 0.65, p <0.005), whereas no
      difference of mean +/- SD was found between BF-FSA and BF-BIA. CONCLUSION: FSA
      and BIA are almost comparable techniques to assess both LBM and BF, although FSA
      is less affected by changes in fluid status. However, assessing LBM in
      normohydration is mandatory. Compared with FSA, BIA is able to establish
      hydration status and lacks depency on operator interpretation. Therefore, in
      routine patient care the BIA technique is the one to be preferred.

PMID- 9543601
TI  - Transferrin receptor assay and zinc protoporphyrin as markers of iron-deficient
      erythropoiesis in end-stage renal disease patients.
AB  - To evaluate storage iron deficiency and iron-deficient erythropoiesis we
      determined, in a cross-sectional study of 95 patients mainly including end-stage
      renal disease patients (ESRD) with (32) and without rh-EPO therapy (55), the
      following parameters: hemoglobin, mean corpuscular red cell volume, ferritin,
      transferrin saturation (TS), zinc protoporphyrin (ZPP) and soluble transferrin
      receptor (TfR). In the dialysis group the percentage of positive samples with
      each marker of tissue iron supply defined as TS < 20%, ZPP > 40 mumol/mol Heme
      and TfR > 3.05 microgram/ml was as follows: TS 43.7% and 32.2% at a diagnostic
      threshold level of < 16%, ZPP 33.3% and TfR 17.2%. Manifest storage iron
      deficiency defined as ferritin < 30 ng/ml was observed in 5.7% of the samples
      while the mean ferritin concentration of the rh-Epo treated dialysis patients was
      509.3 ng/ml compared to 262.5 ng/ml in the group without rh-EPO therapy. These
      data reflect a generous iron substitution in our series taking a TS < 20% as an
      intervention criterion. Looking at the different results of the three markers the
      best correspondence was found between ZPP and TfR resulting in a weak positive
      correlation (+0.64). In conclusion, we found quite different results with
      different assays when evaluating endogenous iron availability in our series of
      mainly ESRD patients in a cross-sectional study. Because a gold-standard is not
      defined further firm conclusions cannot be drawn from this type of study. The
      adequacy of the different parameters of iron metabolism including threshold
      levels and, consequently, the decision and route of iron substitution deserve an
      evaluation in a longitudinal study to characterize the best marker or marker
      combination in this setting.

PMID- 9543602
TI  - Thrombotic thrombocytopenic purpura accompanied by transient pure red cell
      aplasia and thymoma.
AB  - We describe a 64-year-old man with thrombotic thrombocytopenic purpura (TTP),
      transient pure red cell aplasia (PRCA) and thymoma. TTP in this case was thought
      to be idiopathic and was accompanied by microangiopathic hemolytic anemia. The
      patient, therefore, had an aplastic crisis due to PRCA. He was treated with
      peritoneal dialysis, plasma exchange with plasma infusion, red blood cell
      transfusion, methylprednisolone pulse therapy followed by maintenance dosing with
      intravenous prednisolone, gamma-globulin, vincristine, and dipyridamol. As a
      result, the patient's mental disorder, acute renal failure, anemia and
      thrombocytopenia improved; however, the haptoglobin level remained low. The
      pathogenesis of PRCA and thymoma indicates that these are immunological disorders
      often associated with each other. To our knowledge, there are no reports of TTP
      with transient PRCA and thymoma. Although such a combination is considered
      relatively rare, this case suggests that there is an immunological contribution
      to the pathogenesis of the association of these disorders.

PMID- 9543603
TI  - Fungal bezoars as a cause of renal insufficiency in neonates and infants-
      recommended treatment strategy.
AB  - Fungal bezoars may be a cause of urinary tract obstruction and acute renal
      failure in neonates and young infants. We describe a female very low birth weight
      infant (25+3 weeks, 795 gram) who developed renal insufficiency on the basis of
      systemic fungal infection with fungal bezoars in both kidneys. The girl was
      treated by local irrigation of the kidneys and bladder with amphotericin B via
      percutaneously inserted bilateral nephrostomy catheters, in combination with
      intravenous fluconazol. Renal function subsequently improved and after 11 weeks
      of treatment the bezoars had disappeared sonographically. Follow-up of this child
      and the one we similarly treated for fungal bezoars before, however, shows
      suboptimal renal function as assessed by the clearance of creatinine and the
      mercapto acetyl triglycine scan (MAG III). Until now, insufficient data are
      available yet to assess with certainly the long-term effects of fungal bezoars on
      renal function. Based on our experience and a review of the recent literature
      (1980-1996) on systemic candidal infections in premature infants, we recommend to
      perform regular renal ultrasound in any case of systemic candidal infection in a
      prematurely born infant. If candidal bezoars are found with pelvic obstruction,
      we suggest to start treatment by the insertion of bilateral nephrostomy catheters
      and local irrigation with amphotericin B in combination with systemic antifungal
      agents, aiming at both the restoration of renal function and the eradication of
      the fungal infection.

PMID- 9543604
TI  - Co-trimoxazole-induced hypouricemia.

PMID- 9543605
TI  - The use of brachial arteriovenous fistulas for hemodialysis.

PMID- 9543606
TI  - Sjogren's syndrome, renal tubular acidosis and nephrocalcinosis.

PMID- 9543607
TI  - Three-dimensional treatment planning for radiotherapy.

PMID- 9543608
TI  - Radiation-induced apoptosis.

PMID- 9543609
TI  - Prognostic factors in invasive carcinoma of the breast.

PMID- 9543610
TI  - An audit of 3D treatment planning facilities and practice in the UK.
AB  - The availability and use of 3D treatment planning facilities in the UK was
      investigated by questionnaire. Fifty-eight of the 62 UK radiotherapy centres
      responded (94%). There was considerable variation in the facilities available and
      in the manner in which they were used. Although 36 centres (62%) have the
      facilities to undertake complex, non-coplanar treatment planning, only 12 did so
      on a regular basis. More surprising was the inconsistent implementation of
      coplanar CT planning. It is suggested that we need to work towards reaching a
      consensus on best practice in radiotherapy planning. This will require the
      creation of systems for guidance and further training of the various staff
      involved.

PMID- 9543611
TI  - Variations in referral pattern for postoperative radiotherapy of patients with
      screen-detected breast cancer in the south Thames (east) region.
AB  - This paper describes the findings of a region-wide audit undertaken in 1995-1996
      of post-operative radiotherapy treatment for patients with screen-detected breast
      cancer. The study covers the first 3 years from the start of the South Thames
      (East) Breast Screening Programme in June 1988 up to March 1992. The audit shows
      that only 60% of the patients with invasive carcinoma who were treated by
      conservation surgery are known to have received radiotherapy. A considerable
      variation in referral patterns was observed across the region. Analysis suggests
      that whilst geographical, patient choice and tumour factors may play an important
      role in the selection of patients for radiotherapy treatment after conservative
      surgery for early breast cancer, management protocols of surgical units were the
      most critical factor, and that these appear to vary, depending on the level of
      involvement of the clinician with the screening programme (as measured by case
      load).

PMID- 9543612
TI  - Variation in postoperative radiotherapy delivery for patients with screen
      detected breast cancer in the south Thames (east) Region.
AB  - This paper stems from a region-wide audit of postoperative radiotherapy treatment
      for patients with screen-detected breast cancer, commencing from the start of the
      South Thames (East) screening programme in June 1988 and ending in March 1992. It
      reports on the variation in treatment practices amongst clinical oncologists in
      the region. There was diversity in treatment schedules, dose specification
      points, and the use of lymph node radiotherapy, breast boost and interstitial
      implants. While local protocols vary by centre and individual oncologist, many
      treatment decisions appear to have been dictated by the availability of machines
      and other resources. However, further analysis suggests that the variation is
      within the same range as that described in the nationwide survey of breast
      radiotherapy by the Audit Office of the Royal College of Radiologists in 1995 [1
      3].

PMID- 9543614
TI  - Magnetic resonance imaging of the whole spine in suspected malignant spinal cord
      compression: impact on management.
AB  - Patients with suspected malignant spinal cord compression may present with a
      misleading sensory level or have multiple levels of compression that are not
      apparent clinically or on imaging of a limited area of the spine. To estimate how
      often this occurs and to evaluate a policy of magnetic resonance imaging (MRI) of
      the whole spine for any patient with suspected cord compression, data from 127
      patients who had undergone MRI scans of the whole spine were reviewed. In 85 of
      127 scans, there was evidence of compression of or impingement upon the spinal
      cord. A sensory level was present in 47 of these 85 patients, but in 12/47 (26%)
      the sensory level was four or more segments below or three or more segments above
      the actual lesion. Multiple levels of compression or impingement were found in 33
      of 85 (39%) patients; in 24 of these, more than one region
      (cervical/thoracic/lumbar) of the cord was involved. For 32 patients who
      commenced radiotherapy to a treatment volume based on clinical criteria before
      the MRI scan was available, the radiotherapy fields needed modification in 16
      (50%) as a result of the MRI findings. The results support a policy of MRI of the
      whole spine in any patient with suspected malignant spinal cord compression.

PMID- 9543613
TI  - The effect of cimetidine on the pharmacokinetics of epirubicin in patients with
      advanced breast cancer: preliminary evidence of a potentially common drug
      interaction.
AB  - Epirubicin is known to be metabolized in the liver. Therefore, drugs such as
      cimetidine, which inhibit the cytochrome P-450 enzyme system or reduce liver
      blood flow, may reduce the plasma clearance of epirubicin. In a small study,
      epirubicin 100 mg/m2 every 3 weeks was administered intravenously to eight
      patients, who also received oral cimetidine (400 mg b.d. for 7 days starting 5
      days before chemotherapy) with either the first or second cycles. Epirubicin
      pharmacokinetics and liver blood flow (idocyanine green clearance) were assessed
      at each course. The areas under the plasma concentration time curves (AUCs) were
      used to compare the systemic exposure to epirubicin and its metabolites with each
      course. The estimated median percentage increase (95% confidence interval CI) in
      the AUC with cimetidine were: epirubicin 50% (95% CI -18 to 193, epirubicinol 41%
      (95% CI 1 to 92). Despite the small numbers studied, the increase in the active
      metabolite epirubicinol was significant (P < 0.05). These changes in exposure
      were not explained by reduced cytochrome P-450 activity as the 7-deoxy
      doxorubicinol aglycone AUC was not reduced (357% increase: 95% CI 17 to 719) or
      by a decrease in liver blood flow (17% increase: 95% CI -39 to 104). Cimetidine
      is likely to be coprescribed or self-administered with epirubicin and therefore
      clinicians should be aware of this potential interaction.

PMID- 9543615
TI  - Bone density: is it affected by orchidectomy and radiotherapy given for stage I
      seminoma of the testis?
AB  - A cross-sectional study of bone density involving 30 patients who had undergone
      orchidectomy and para-aortic radiotherapy for Stage I seminoma of the testis, has
      been performed. Bone density measurements were made of the whole body, lumbar
      spine and hips, including all irradiated areas. Comparison was made with
      previously obtained standard sex and age matched control data. The 30 patients
      treated for seminoma had a significantly increased mean bone density compared
      with age matched normal values. No significant differences were demonstrated
      between the mean bone densities of the irradiated and non-irradiated hips. There
      was no significant relationship between bone density measurement and time since
      orchidectomy or radiotherapy. These results suggest that nodal irradiation for
      seminoma has little long term effect on bone density.

PMID- 9543616
TI  - Evolution and development of hospice and specialist palliative care services.

PMID- 9543617
TI  - Germ cell cancer and dermatomyositis.
AB  - Although the association of dermatomyositis and malignancy is well recognized,
      there have been few previous reports of germ cell tumours occurring in this
      context. Two cases of teratoma with dermatomyositis have presented at the Wessex
      Medical Oncology Unit in Southampton, which prompted a review of the literature.

PMID- 9543618
TI  - Tuberculosis of the nasopharynx following radiotherapy.
AB  - We report the case history of a patient who was treated with radiotherapy for
      nasopharyngeal carcinoma. During follow-up, she showed signs, symptoms and
      radiological evidence of disease recurrence and progression. However, repeated
      biopsies of the posterior nasal space (PNS) failed to demonstrate malignancy. A
      diagnosis of nasopharyngeal tuberculosis was finally made when tissue from a PNS
      biopsy stained positive for acid-fast bacillus. The patient responded to
      antituberculous chemotherapy.

PMID- 9543619
TI  - An unusual case of carotid body tumour.
AB  - Carotid body tumours are uncommon but fascinating lesions, which arise from
      paraganglionic tissue at the bifurcation of the common carotid artery. We report
      the case history of a 40-year-old female patient who presented initially with a
      malignant left-sided tumour, followed by a right-sided tumour 17 years later.
      Although there is no known family history, it is likely, because of the bilateral
      tumours and the young age at presentation, that the tumour was inherited in this
      patient. The literature on carotid body tumours is reviewed, with particular
      emphasis on malignant and multiple tumours and their treatment. We discuss the
      recently elucidated mechanism of inheritance and its implications for affected
      patients and their families.

PMID- 9543620
TI  - Interstitial pneumonitis as a late complication of high dose therapy with
      cyclophosphamide/thiotepa and peripheral blood progenitor cell rescue for
      carcinoma of the breast.

PMID- 9543621
TI  - Where next in the treatment of rectal cancer.

PMID- 9543622
TI  - Prenatal care.
AB  - This paper describes the psychological and psychosocial aspects of prenatal care,
      which are believed to be of particular importance for medical/psychological
      practice. The emotional changes that "normally" take place during pregnancy are
      surveyed and evidence is provided linking these changes with potential adverse
      effect on pregnancy and labour. The salience of anxiety and life stresses in
      pregnancy research is highlighted as well as their intricate inverse relationship
      with social support. Antenatal classes are offered as an example of social
      support provision. The different kinds of such classes and evaluation of their
      effectiveness are briefly presented, as well as a number of controlled trials of
      enhanced support during pregnancy. Finally, the effect provision of prenatal care
      has on women as well as their role in their own care are raised. The need is
      stressed for further sophisticated longitudinal and multivariate research
      exploring further the causative links between quality of prenatal care, pregnancy
      outcome, and subsequent child development.

PMID- 9543623
TI  - Meta-analytic investigation of the effectiveness of self-regulatory components in
      the treatment of adult problem behaviors.
AB  - The present paper utilized meta-analysis to examine the effectiveness of
      interventions in which components of self-regulation theories (e.g., self
      monitoring, self-reinforcement) were the primary treatment intervention utilized
      in treating habit disturbances, depression, anxiety and health-related problems
      with adults. The effect size (ES)1 comparing interventions utilizing all
      combinations of self-regulatory components to no intervention at all was d = .25
      (p < .005). The ES comparing interventions utilizing self-monitoring (SM) plus
      any other self-regulatory component(s) to interventions utilizing SM alone was d
      = .42 (p < .001). Differential effectiveness was demonstrated for various
      combinations of self-regulatory components.

PMID- 9543624
TI  - A review of instruments for assessing family history.
AB  - The influence of family history on one's development has long been a focus of
      psychological theory, research, and practice. In recent years, however,
      conceptualizations of family influences on development have evolved considerably,
      and there has also been increased concern about the reliability of individuals'
      memory for their childhoods in general. Current knowledge regarding these and
      other issues are applied to reviewing the instruments that have been developed to
      assess aspects of family history. The complexity of this type of assessment is
      emphasized, and a variety of problems with the reliability and validity of the
      currently available instruments are discussed. Suggestions for future research
      are also offered.

PMID- 9543625
TI  - Psychiatric rehabilitation: efficacy of four models.
AB  - This paper is a critical review of four major rehabilitation programs: assertive
      community treatment, case management, vocational rehabilitation, and educational
      rehabilitation. Reported outcomes are reviewed in the context of study design,
      service characteristics, client characteristics, and operationalization of
      outcomes. Findings from the four programs are compared with one another. The
      authors concluded that clients are able to learn most of the skills taught,
      independently of the rehabilitation model. Furthermore, skills learned in one
      life domain generalized to a moderate extent to other areas. The four
      rehabilitation programs had varied effects on the outcome variables, and part of
      the variability in the findings appears to be related to client characteristics.
      Limitations of the studies reviewed are identified and a set of recommendations
      was suggested for the future practice of research into psychiatric
      rehabilitation.

PMID- 9543626
TI  - The Behavior Management Flow Chart: a component analysis of behavior management
      strategies.
AB  - Representative published child behavior management research was reviewed. Based
      upon the review, a task analysis of child behavior management strategies was
      conducted. The Behavior Management Flow Chart is a flow chart of the task
      analysis that synthesizes the research into a cohesive unit and visually depicts
      actions that adults may be trained to use to manage misbehavior displayed by
      disruptive children. A discussion compares and contrasts the Behavior Management
      Flow Chart with Hanf-model behavior management programs, the appropriate unit of
      analysis is examined, and concerns regarding integrating a wide range of research
      variables into a unitary model are addressed.

PMID- 9543627
TI  - Protein-tyrosine phosphatases: biological function, structural characteristics,
      and mechanism of catalysis.
AB  - The protein-tyrosine phosphatases (PTPases) superfamily consists of tyrosine
      specific phosphatases, dual specificity phosphatases, and the low-molecular
      weight phosphatases. They are modulators of signal transduction pathways that
      regulate numerous cell functions. Malfunction of PTPases have been linked to a
      number of oncogenic and metabolic disease states, and PTPases are also employed
      by microbes and viruses for pathogenicity. There is little sequence similarity
      among the three subfamilies of phosphatases. Yet, three-dimensional structural
      data show that they share similar conserved structural elements, namely, the
      phosphate-binding loop encompassing the PTPase signature motif (H/V)C(X)5R(S/T)
      and an essential general acid/base Asp residue on a surface loop. Biochemical
      experiments demonstrate that phosphatases in the PTPase superfamily utilize a
      common mechanism for catalysis going through a covalent thiophosphate
      intermediate that involves the nucleophilic Cys residue in the PTPase signature
      motif. The transition states for phosphoenzyme intermediate formation and
      hydrolysis are dissociative in nature and are similar to those of the solution
      phosphate monoester reactions. One strategy used by these phosphatases for
      transition state stabilization is to neutralize the developing negative charge in
      the leaving group. A conformational change that is restricted to the movement of
      a flexible loop occurs during the catalytic cycle of the PTPases. However, the
      relationship between loop dynamics and enzyme catalysis remains to be
      established. The nature and identity of the rate-limiting step in the PTPase
      catalyzed reaction requires further investigation and may be dependent on the
      specific experimental conditions such as temperature, pH, buffer, and substrate
      used. In-depth kinetic and structural analysis of a representative number of
      phosphatases from each group of the PTPase superfamily will most likely continue
      to yield insightful mechanistic information that may be applicable to the rest of
      the family members.

PMID- 9543628
TI  - Enzymes in low water systems.
AB  - Water is fundamental for enzyme action and for formation of the three-dimensional
      structure of proteins. Hence, it may be assumed that studies on the interplay
      between water and enzymes can yield insight into enzyme function and formation.
      This has proven correct, because the numerous studies that have been made on the
      behavior of water-soluble and membrane enzymes in systems with a low water
      content (reverse micelles or enzymes suspended in nonpolar organic solvents) have
      revealed properties of enzymes that are not easily appreciated in aqueous
      solutions. In the low water systems, it has been possible to probe the relation
      between solvent and enzyme kinetics, as well as some of the factors that affect
      enzyme thermostability and catalysis. Furthermore, the studies show that low
      water environments can be used to stabilize conformers that exhibit unsuspected
      catalytic properties, as well as intermediates of enzyme function and formation
      that in aqueous media have relatively short life-times. The structure of enzymes
      in these unnatural conditions is actively being explored.

PMID- 9543629
TI  - An immortalized hamster corneal epithelial cell line for studies of the
      pathogenesis of Acanthamoeba keratitis.
AB  - PURPOSE: The protozoan Acanthamoeba produces a severe keratitis in a small
      percentage of people, especially contact lens-wearers. The purpose of this work
      was to develop and characterize an immortalized line of hamster corneal
      epithelial cells to be used in studies of the pathogenesis of Acanthamoeba
      keratitis. METHODS: Hamster corneal epithelial cells were maintained in primary
      culture and immortalized using simian virus 40 (SV40). Foci of transformed cells
      were cloned and subsequently characterized by phase-contrast microscopy and
      immunocytochemistry. Growth characteristics of the clone that were analyzed
      included loss of dependence on conditioned medium and ability to grow in soft
      agar. Cytotoxicity experiments were performed, to determine whether the selected
      clone was susceptible to Acanthamoeba infection in vitro. RESULTS: A cell line
      which exhibited epithelial morphology, as determined by phase contrast
      microscopy, was selected and cloned. Immunocytochemistry demonstrated the
      presence of keratin in the cloned cells, confirming the epithelial nature of the
      cell line. Immortalization was shown by loss of dependence on fibroblast
      conditioned medium, ability to form colonies in soft agar and no apparent
      senescence following numerous passages in culture. This cell line was found to be
      sensitive to the cytotoxic effects of a pathogenic strain of Acanthamoeba.
      CONCLUSIONS: An immortalized line of hamster corneal epithelial cells was
      developed. This clone is susceptible to infection with Acanthamoeba and will be a
      useful tool with which to investigate the pathogenesis of Acanthamoeba keratitis.

PMID- 9543630
TI  - Environmental factors influence P. aeruginosa binding to the wounded mouse
      cornea.
AB  - PURPOSE: To determine whether environmental factors or bacterial viability affect
      the binding of two strains of P. aeruginosa to mouse cornea. METHODS: Scarified
      corneas were placed in organ culture and inoculated with P. aeruginosa cell
      suspensions containing either ATCC 19660 or PAO1 bacterial strains classed as
      cytotoxic or invasive, respectively. Eyes were incubated in vitro for 1 h after
      bacterial application at different pH or temperature conditions or in PBS
      containing various divalent cations. The adhesion of heat-killed or formalin
      fixed bacteria was tested similarly. Scanning electron microscopy (scanning EM)
      was used to quantitate adherent bacteria. RESULTS: P. aeruginosa ATCC 19660
      showed an increase in binding at pH 8.0, favored higher temperatures and required
      both calcium and magnesium for optimum binding. Adherence of PAO1 was enhanced at
      pH 6.5 and decreased at pH 8.0. This strain favored binding at lower temperatures
      and did not require either divalent cation for optimum binding. In addition, the
      presence of magnesium ions resulted in reduced binding for this strain. Both
      strains exhibited less binding ability after formalin fixation or heat killing.
      CONCLUSION: Environmental factors and bacterial viability are important factors
      which influence the ability of both cytotoxic and invasive strains of P.
      aeruginosa to bind to the scarified cornea.

PMID- 9543631
TI  - Localization of TIMP-1, TIMP-2, TIMP-3, gelatinase A and gelatinase B in
      pathological human corneas.
AB  - PURPOSE: Determine the tissue distribution patterns for tissue inhibitors of
      metalloproteinases (TIMP-1, TIMP-2, TIMP-3), gelatinase A and gelatinase B in
      normal and pathologic corneas. METHODS: Corneas were examined by
      immunohistochemistry, using antibodies to TIMP-1, TIMP-2, TIMP-3, gelatinase A or
      gelatinase B. RESULTS: In normal corneas, TIMP-1 antibody stained the epithelium
      and endothelium. TIMP-2 and TIMP-3 stained the epithelium, keratocytes and
      endothelium. Gelatinase A staining was weak and restricted to the epithelial
      cells. Radial keratotomy scars showed increased staining for TIMP-1 and TIMP-2
      around the epithelial cell plug and along the incision. Bullous keratopathy
      corneas showed TIMP staining patterns similar to normal corneas and increased
      gelatinase A staining in regions of subepithelial fibrosis. Stromal scars of
      keratoconus corneas also had increased staining with TIMP-1 and TIMP-2
      antibodies. In many keratoconus corneas, the TIMP-3 staining pattern was similar
      to normal corneas. However, in some keratoconus corneas, when Bowman's layer was
      missing, the stroma beneath was completely devoid of TIMP-3 antibody staining. No
      gelatinase B was seen in either the normal or diseased corneas. CONCLUSION: These
      data suggest that TIMP-1 and TIMP-2 are important for scar formation and corneal
      remodeling, since they were found in increased amounts at radial keratotomy
      incision sites and keratoconus scars. The significance of the focal stromal
      defects in TIMP-3 staining, associated with absence of Bowman's layer on
      keratoconus corneas, needs to be elucidated. At the stages of disease examined in
      this study, gelatinase B may not play a significant role in these pathological
      processes, since it was not seen in any of the corneas examined.

PMID- 9543632
TI  - Quantitation of asparagine-101 deamidation from alpha-A crystallin during aging
      of the human lens.
AB  - PURPOSE: To quantitate deamidation of asparagine-101 from the alpha-A crystallin
      protein of human lenses of different ages. METHODS: Alpha-A crystallin was
      purified from total proteins of human lenses of different ages, followed by
      tryptic digestion and resolution of the peptides, using reverse phase
      chromatography. Known amounts of synthetic peptide standards, corresponding to
      the amidated and deamidated forms of the expected tryptic peptide containing
      asparagine-101, were used to identify and quantitate the amount of deamidation.
      RESULTS: From 0-30 yrs of age, approximately 45% of asparagine-101 was
      deamidated, while only approximately 5% additional deamidation occurred during 30
      68 yrs of age. CONCLUSIONS: In the normal human lens, most deamidation of
      asparagine-101 occurs during the first approximately 30 years of age, followed by
      a small additional amount of deamidation (approximately 5%) during the next
      approximately 38 years, resulting in a maximum of approximately 50% deamidation
      during the lifetime of the individual.

PMID- 9543633
TI  - The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not
      influenced by aminoguanidine treatment.
AB  - PURPOSE: To examine the levels of the free radical protecting enzyme glutathione
      and the endothelial/pericyte ratio in retinal capillaries in the Goto-Kakizaki
      (GK) Wistar rat, with and without aminoguanidine treatment. METHODS: Eight-month
      old GK rats, with non-obese, spontaneous non-insulin-dependent diabetes mellitus
      (NIDDM), were examined after a six month period of aminoguanidine treatment.
      Glutathione levels were measured with high performance liquid chromatography and
      the endothelial/pericyte ratio was calculated in trypsin digested vessel
      preparations. RESULTS: The levels of glutathione in GK rat retina were
      significantly lower compared to controls (p = 0.0108). There was no difference in
      the endothelial/pericyte ratio compared to matched control rats (1.8 +/- 0.2 vs.
      1.8 +/- 0.1, respectively). Aminoguanidine treatment did not influence either the
      degree of hyperglycemia, the levels of glutathione or the endothelial/pericyte
      ratio in GK or control rat retina. CONCLUSIONS: The results indicate that
      impaired glucose metabolism may influence one of the defense mechanisms for
      oxidative stress, but also suggest that decreased glutathione levels occur prior
      to morphological signs of pericyte loss and/or endothelial cell proliferation in
      this animal model of hereditary NIDDM.

PMID- 9543634
TI  - Tear fluid content of electrochemically active components including water soluble
      antioxidants.
AB  - PURPOSE: To describe the content of water-soluble antioxidants in tear fluid.
      METHODS: We collected tear fluid from healthy subjects, either into borosilicate
      glass tubing or by absorption onto Schirmer strips. High pressure liquid
      chromatography with electrochemical detection provided data on several components
      in a single assay. The system was sufficiently sensitive to provide reliable
      values for components present in tear fluid collected at normal (basal) or
      stimulated rates of secretion. RESULTS: Tear fluid at basal secretion was found
      to contain four compounds often considered to function in biology as
      antioxidants. Ascorbic acid (AA) is found at 665 microM, tyrosine at 45 microM
      and glutathione (GSH) at 107 microM. Cysteine (48 microM) and uric acid (328
      microM) are reported for the first time; the latter is somewhat controversial as
      a physiologically active antioxidant. One peak on the chromatogram was
      consistently present but has not been identified. During stimulation of flow by
      brief inhalation of ammonium hydroxide fumes, the concentration of each compound
      was lower. CONCLUSION: This work demonstrates the presence of electro-chemically
      active components that might function as antioxidants at the anterior surface of
      the cornea against potential damage from radiation, oxygen toxicity, abrasion and
      environmental chemicals.

PMID- 9543635
TI  - Molecular biology and electrophysiology of calcium-activated potassium channels
      from lens epithelium.
AB  - PURPOSE: We structurally and functionally characterized the alpha and beta
      subunits of the human lens epithelium Ca(++)-activated potassium channel (BK).
      METHODS: The two subunits were sequenced following RT-PCR with multiple primer
      pairs. The subunits were cloned using a PCR approach and were expressed in tsA
      201 cells for patch clamp recording. Green fluorescence protein-channel subunit
      fusion proteins were characterized by patch clamping and were imaged by
      fluorescence microscopy. RESULTS: Alpha subunits alone make a large single
      channel conductance, potassium-selective channel with modest Ca++ sensitivity.
      Beta subunits alone make no channel but, when coexpressed with the alpha subunit,
      make a channel with increased Ca++ sensitivity, although still less than for
      natural channels of this type. GFP-BK subunit fusion proteins continue to
      function and result in a fluorescing channel, which can be localized by
      fluorescence microscopy. The alpha subunit codes for a "minimal" BK channel in
      that none of its potential alternative splicing sites contains an "extra" exon.
      CONCLUSIONS: The Ca(++)-activated potassium channel known as BK has the
      nucleotide sequences of its alpha and beta subunits represented in messenger RNA
      of cultured human lens epithelium. It is the first identified channel, to date,
      which imparts internal Ca++ dependence to lens epithelial potassium conductance.

PMID- 9543636
TI  - Growth factor and cytokine modulation of trabecular meshwork matrix
      metalloproteinase and TIMP expression.
AB  - PURPOSE: We hypothesize that regulated trabecular extracellular matrix (ECM)
      turnover, initiated by the matrix metalloproteinases, is critical for the
      maintenance of normal aqueous humor outflow rates. However, very little is known
      about the regulation of trabecular ECM turnover. To identify candidate trabecular
      regulators, we evaluated the effects of several growth factors and cytokines on
      trabecular matrix metalloproteinase and TIMP expression. METHODS: Porcine
      trabecular meshwork cells were treated with several doses of a variety of growth
      factors and cytokines and culture media was analyzed after 24, 48, and 72 h.
      Zymograms were used to evaluate stromelysin, gelatinase A and B activity levels,
      while immunoblots of Western transfers were used to evaluate stromelysin,
      collagenase, TIMP-1 and TIMP-2 protein levels. RESULTS: A phorbol mitogen (TPA),
      and TNF alpha and beta, interleukin-1 alpha and PDGF BB stimulate gelatinase B,
      stromelysin, interstitial collagenase and TIMP-1 expression, while having
      negligible effects on gelatinase A expression; TIMP-2 levels are reduced by TNF
      but not affected by the other treatments. Acidic and basic FGF, IL-1 beta, TGF
      beta and PDGF AB produce similar but smaller effects, while HGF, VEGF, EGF, KGF,
      and LIF produce small to moderate elevations in stromelysin with minimal other
      responses. PDGF AA, gamma INF, oncostatin-M and endothelin-1 produce negligible
      changes in these proteinases and inhibitors. CONCLUSIONS: In addition to
      providing potential ways to modulate trabecular metalloproteinase and TIMP
      levels, the responsiveness of these cells to some of these growth factors and
      cytokines suggests possible roles in normal or pathogenic trabecular cell
      regulation and some may affect aqueous humor outflow.

PMID- 9543638
TI  - Epidermal growth factor stimulates phospholipase D independent of phospholipase
      C, protein kinase C or phosphatidylinositol-3 kinase activation in immortalized
      rabbit corneal epithelial cells.
AB  - PURPOSE: Activation of phospholipase D (PLD) is believed to be an important
      signaling pathway involved in cell growth and differentiation in several tissues,
      in response to a variety of mitogens. The aim of the present study was to
      investigate the effect of epidermal growth factor (EGF) on PLD activity in rabbit
      corneal epithelial cells (RCEC). We have also examined whether the EGF effect is
      dependent on concurrent activation of phospholipase C (PLC), protein kinase C
      (PKC) or phosphatidylinositol 3-kinase (PI-3-kinase) in these cells. METHODS:
      RCEC, immortalized with adenovirus SV-40, were cultured until they became
      confluent. The cells were labeled with [3H]myristic acid and incubated with or
      without EGF or other agents for specified time intervals. PLD activity was
      measured by quantifying [3H]phosphatidylethanol in cells incubated in the
      presence of ethanol. PLC activity was determined by measuring the radioactivity
      in inositol trisphosphate in myo[3H]inositol-labeled RCEC. PI 3-kinase activity
      was assessed by measuring the production of PIP3 in 32P-labeled cells. RESULTS:
      Addition of EGF to RCEC stimulated PLD activity in a time- and dose-dependent
      manner. The maximal effect was observed with 150 ng/ml EGF and at 10 min of
      incubation. The PLD activity was also stimulated when phorbol myristate acetate
      (PMA) was added to the cells. Treatment of the cells with EGF stimulated PLC
      activity which was inhibited by U73122, a PLC inhibitor. Under the same
      experimental conditions, the inhibitor had no effect on EGF-stimulated PLD
      activity. Down-regulation of PKC or treatment of the cells with RO31-8220, a PKC
      inhibitor, inhibited the PMA- but not EGF-stimulated PLD activity. Incubation of
      the cells with wortmannin, a PI 3-kinase inhibitor, abolished the EGF-stimulated
      PI 3-kinase activity, but potentiated the EGF-stimulated PLD activity. The EGF
      effect was inhibited by treatment of the cells with tyrphostin B42, a receptor
      tyrosine kinase inhibitor. CONCLUSIONS: These results indicate that EGF
      stimulates PLD activity in RCEC by a mechanism that involves tyrosine
      phosphorylation of a protein(s) in the cascade of biochemical reactions initiated
      by EGF-receptor interaction, and it is not dependent on concurrent activation of
      PKC, PLC, or PI 3-kinase in these cells.

PMID- 9543637
TI  - TGF-beta s stimulate cell proliferation via an autocrine production of FGF-2 in
      corneal stromal fibroblasts.
AB  - PURPOSE: Although transforming growth factor-betas (TGF-beta s) inhibit
      epithelial cell proliferation, these same substances stimulate cell proliferation
      of fibroblasts. In order to elucidate the mechanism of stimulatory activity of
      TGF-beta on fibroblast, the present study was performed to determine whether TGF
      beta might be an indirect mitogen acting through induction of an endogenous
      growth factor(s) that then acts as the direct mitogen in an autocrine manner in
      corneal stromal fibroblasts (CSFs). METHODS: Cell proliferation was determined
      either by counting cell numbers or by analyzing the incorporation of [3H]
      thymidine into DNA. The synthesis of TGF-beta, TGF-beta receptors, FGF-2 and p27
      was analyzed by immunoprecipitation and immunoblotting. RESULTS: TGF-beta 1, TGF
      beta 2, and TGF-beta 3 significantly stimulated cell proliferation of CSFs in a
      dose-dependent manner. The medium conditioned by CSFs and subsequently activated
      by acid-inhibited cell proliferation of corneal endothelial cells by 40%. When
      the acid-activated media conditioned by CSFs were immunoprecipitated with either
      combined anti-TGF-beta 1 and TGF-beta 2 antibodies or anti-TGF-beta 3 antibody,
      all three TGF-beta s, with an apparent molecular size of 25 kDa, were detected,
      whereas CSFs produced an 80-kDa latent form of TGF-beta 1. These cells can also
      express TGF-beta type II receptor and betaglycan. Interestingly, CSFs produced
      and secreted 18-kDa FGF-2, the synthesis of which is further stimulated by either
      TGF-beta 1 or TGF-beta 3, while both the neutralizing antibody to FGF-2 and the
      FGF-2 specific antisense oligonucleotide primers significantly inhibited the
      stimulatory activities of TGF-beta 1 in CSFs. The expression of p27, a negative
      regulator in cell cycle, was not altered by TGF-beta. CONCLUSIONS: These findings
      indicate that CSFs produce both TGF-beta s and FGF-2 and that FGF-2 appears to be
      a direct stimulator for TGF-beta-mediated cell proliferation in CSFs.

PMID- 9543639
TI  - Augmented retinal endothelin-1, endothelin-3, endothelinA and endothelinB gene
      expression in chronic diabetes.
AB  - PURPOSE: Endothelins (ETs) belong to a family of vasoactive peptides implicated
      in several disorders of the microvasculature. In the present study, we
      investigated ET-1 and ET-3 peptide mRNAs and ETA, ETB receptor mRNAs in the
      retina of diabetic BB/W rats and age-matched, non-diabetic control animals,
      following six months of diabetes. METHODS: Total mRNA was extracted from each
      retina and was subjected to reverse transcriptase polymerase chain reaction for
      ET-1, ET-3, ETA and ETB. Simultaneously, beta-globin was amplified and used as a
      housekeeping gene. The products were analyzed on agarose gels and the specificity
      of the amplification was established by hybridization with amplification-specific
      biotinylated oligoprobes. For quantification, the products from the linear phase
      of amplification were subjected to serial dilution slot-blot hybridization and
      densitometry. RESULTS: ETs and their receptor mRNA expressions were present in
      the retina. Retinas from the diabetic animals showed significant increases in ET
      1, ET-3 ET(A), ET(B) mRNA expressions compared to those from control rats.
      CONCLUSIONS: These findings indicate that retinal ET-1, ET-3, ET(A) and ET(B)
      mRNA expression in increased in the chronically diabetic BB/W rat. Augmented gene
      expression of ETs and their receptors potentially may be of importance in the
      pathogenesis of retinal microangiopathy in diabetes.

PMID- 9543640
TI  - Effects of nitric oxide synthase inhibitor on intraocular pressure and ocular
      inflammation following laser irradiation in rabbits.
AB  - PURPOSE: To examine the effects of nitric oxide synthase (NOS) inhibitors on
      intraocular pressure (IOP) and ocular inflammation following laser irradiation of
      the rabbit iris, and to investigate the involvement of nitric oxide (NO).
      METHODS: Thirty min after the intravenous administration of a nonselective
      inhibitor of NOS, N omega-nitro-L-arginine methyl ester (L-NAME, 1-100 mg/kg), or
      a selective inhibitor of iNOS, aminoguanidine (AG, 100 mg/kg), Q-switched Nd:YAG
      laser irradiation was applied to the iris of albino rabbits at an energy level of
      48 mJ. IOP was measured prior to and for 24 h after irradiation. In separate
      groups of rabbits, aqueous humor was withdrawn 30 min after irradiation to
      determine protein and prostaglandin (PG) E2 concentrations. RESULTS:
      Intravenously administered L-NAME dose-dependently inhibited the acute increase
      in IOP, the peak of which was observed at 30 min, following laser irradiation.
      The IOP increase was completely abolished by 100 mg/kg of L-NAME. This dose of L
      NAME significantly reduced the elevation of protein concentration in aqueous
      humor following irradiation; however, this dose failed to affect the increase in
      PGE2 concentration On the other hand, the inhibitory effects of AG (100 mg/kg) on
      the increase in IOP and aqueous protein following laser irradiation were not
      significant. CONCLUSIONS: Intravenous administration of L-NAME significantly
      inhibits the IOP rise and the increase in protein concentration in aqueous humor
      following laser irradiation, but AG does not, suggest the involvement of cNOS in
      these ocular responses to laser irradiation.

PMID- 9543641
TI  - Recombinant adenovirus-mediated gene transfer into the adult rat retina.
AB  - PURPOSE: The present study was designed to evaluate the feasibility of gene
      transfer into the retina of adult rats, using a recombinant replication-defective
      adenovirus vector expressing a reporter gene. METHODS: Purified recombinant
      adenovirus expressing beta-galactosidase (lacZ) (Ad5.hCMV.lacZ) at doses ranging
      from 1.4 x 10(2) to 1.4 x 10(6) plaque-forming units (pfu) were injected into the
      subretinal space of adult Lewis rats. The presence of lacZ was determined by
      histochemical assay and reverse transcription and polymerase chain reaction
      analysis (RT PCR) of total RNA extracted from eyes injected with recombinant
      adenovirus expressing lacZ. RESULTS: As assessed by biomicroscopy, the expression
      of lacZ was highest in the retinal pigment epithelium in a localized area
      corresponding to the site of injection. The level of lacZ expression was
      correlated with the amount of virus delivered to the subretinal space. Persistent
      but decreasing expression of lacZ was noted over time. RT PCR revealed the
      expression of messenger RNA for at least sixty days. CONCLUSIONS: The results of
      this study demonstrate that efficient and stable transfer of genetic material
      into the subretinal space of adult rats may be achieved using a recombinant
      adenoviral vector. The use of such vectors should prove useful in developing
      novel applications and approaches to the study of recombinant protein expression
      in vivo.

PMID- 9543642
TI  - Sharp vision: a prerequisite for compensation to myopic defocus in the chick?
AB  - PURPOSE: Compensatory responses to focusing errors imposed by spectacle lenses in
      chicks, tree shrews and primates leave little doubt that active emmetropization
      can occur, and debate is now centered on whether this process is uni-directional
      or bi-directional in nature. To provide further insight into this emmetropization
      process, the studies reported in this paper addressed the question of whether
      access to sharp vision is necessary for compensation to myopic defocus in the
      chick. METHODS: Two different experimental paradigms were used to address the
      above question: (A) Myopic defocus was imposed, either with +15 or +40 d lenses
      alone or with +15 D lenses on eyes made myopic by 7 days of form deprivation;
      these treatments result in a shift in the plane of focus of the eye (far point)
      to 6.67, 2.5 cm and approximately 3.5 cm resp., with only objects at or closer
      than these planes being in focus. The addition to the lenses of stand-off cones,
      either 2.5 or 5 cm in length, further limited access to (or precluded) sharp
      vision by controlling how closely the chicks could approach objects. One group
      that had sharp vision precluded also underwent optic nerve section. (B) A range
      of positive lenses (+15 to +65 D) were used on their own to impose myopic
      defocus; for the high power lenses, access to sharp vision was very restricted
      because of the close proximity of the new far point (1.54 cm for +65 D lens).
      Refractive errors and axial ocular dimensions were measured in all experiments.
      RESULTS: In the first study (A), preclusion of sharp vision not only prevented
      compensation but resulted in increased eye growth and myopia. This myopia, like
      form-deprivation myopia, was unaltered by optic nerve section surgery. Limiting
      but not precluding sharp vision resulted in partial compensation. In the second
      study (B), good compensation was observed with the +15 D lens but compensation
      progressively declined for higher powers, with the +50 D lens having no apparent
      effect on eye growth and refraction and the +65 D lens inducing myopia instead of
      hyperopia. CONCLUSIONS: Together these results argue that some sharp vision is
      fundamental to compensation to impose myopia. The significance of this new
      finding in relation to the processes underlying active emmetropization is
      discussed.

PMID- 9543643
TI  - A novel homozygous Ile535Asn mutation in the rod cGMP phosphodiesterase beta
      subunit gene in two brothers of a Japanese family with autosomal recessive
      retinitis pigmentosa.
AB  - PURPOSE: Recently, mutations in several genes have been identified as being
      responsible for the pathogenesis of autosomal recessive retinitis pigmentosa
      (arRP). These genes include rhodopsin, beta-subunit of rod cGMP phosphodiesterase
      (PDEB), alpha-subunit of rod cGMP phosphodiesterase (PDEA), and alpha-subunit of
      rod cGMP-gated channel. We here attempted to identify a novel mutation in the
      PDEB gene in Japanese arRP patients. METHODS: Using the PCR-SSCP method,
      sequencing analysis, and restriction endonuclease digestion assay, we analyzed
      the PDEB gene in 17 Japanese families with non-dominant retinitis pigmentosa.
      RESULTS: A novel Ile535Asn mutation was identified in two patients in a single
      family and the mutation cosegregated with RP in this family. Among 90 unrelated
      healthy individuals, no one was identified as homozygous for this mutation,
      except for one individual who was found to be heterozygous. CONCLUSIONS:
      Isoleucine at codon 535 in the PDEB gene is conserved among various mammals.
      Missense mutations of the PDEB gene causing arRP have been reported in a limited
      region (codon 527-codon 699) in which codon 535 is located. Thus, the Ile535Asn
      mutation is an additional missense mutation which is responsible for the
      pathogenesis of arRP.

PMID- 9543644
TI  - Effect of religion and religiosity on alcohol use in a college student sample.
AB  - Two hundred and sixty-three alcohol using college students completed a
      questionnaire on their levels of alcohol use, problems with alcohol use, reasons
      for drinking, perceptions of control over drinking, impulsivity, venturesomeness,
      irrational beliefs, neuroticism, expectations of alcohol effects, depression,
      social norms, religious affiliation and intrinsic and extrinsic religiosity.
      Analyses of variance revealed that students with no religious affiliation
      reported significantly higher levels of drinking frequency and quantity, getting
      drunk, celebratory reasons for drinking and perceived drinking norms than those
      of either Catholic or Protestant religious affiliation, while no significant
      differences across groups were found for alcohol use problems. Protestants
      reported significantly higher levels of perceived drinking control than
      Catholics. Intrinsic religiosity, reflecting one's ego involvement with the
      tenets of one's religion, appeared to play a more important positive role over
      drinking behavior for Protestants than for Catholics.

PMID- 9543645
TI  - Sociodemographic representation in published studies of cocaine abuse
      pharmacotherapy.
AB  - This study evaluated: (1) the reporting of sociodemographic characteristics of
      research subjects in published outpatient studies of cocaine abuse
      pharmacotherapy; (2) the association of study characteristics with such reporting
      and with the distribution of characteristics; and (3) the comparison of
      sociodemographic characteristics in the research subjects with those of a
      community-based sample of cocaine abusers who had sought treatment. Medline
      search identified 68 articles on cocaine abuse outpatient pharmacotherapy
      published from 1983 to 1993 in an English language, peer-reviewed journal.
      Sociodemographic characteristics of research subjects (n = 1802) were compared
      with those of respondents (weighted n = 135) to the National Comorbidity Survey
      (1990-1992), who reported at least one cocaine-related problem and had sought
      substance abuse treatment. Only three (4.4%) articles reported all six of the
      following sociodemographic characteristics of their subjects: 82.4%, reported
      mean age; 58.8%, race/ethnicity; 85.3%, sex; 22.1%, employment status; 13.2%,
      educational status; and 5.9%, socioeconomic status/income. Compared to survey
      respondents, research subjects were significantly more likely to be African
      American and live in the Northeast region of the US and marginally more likely to
      be male and currently unemployed. These findings indicate that many published
      articles do not follow currently recommended guidelines for describing
      sociodemographic characteristics of research subjects and that, aside from
      race/ethnicity and geographic location, research subjects are fairly comparable
      in basic sociodemographic characteristics to the larger population of treatment
      seeking individuals with cocaine-related problems.

PMID- 9543646
TI  - An acute dose of nicotine enhances cue-induced cocaine craving.
AB  - The present study examined whether the active component in tobacco, nicotine, can
      modulate cocaine craving in patients with a history of smoking crack cocaine when
      exposed to crack cocaine related environmental cues. Twenty patients, all
      cigarette smokers, were randomly assigned to nicotine (two 22 mg transdermal
      patches) or placebo in a single-dose, placebo-controlled, crossover, double-blind
      study. Craving and anxiety were measured before and after cocaine cues with
      visual analog scales for desire to use cocaine and mood. Skin conductance and
      skin temperature were recorded before and during cocaine cues. Following exposure
      to cocaine cues, all patients reported an increase in cocaine craving and anxiety
      relative to the pre-cue measures. Cue exposure also produced an increase in skin
      conductance and decrease in skin temperature. The cue-induced increase in cocaine
      craving was strongly enhanced by nicotine, while the increase in anxiety was
      slightly augmented. Cue-induced skin conductance and temperature responses were
      unaffected by nicotine. These findings show that cue-induced cocaine craving is
      enhanced by nicotine. This occurred in the absence of any tobacco smoking-related
      cues, suggesting that nicotine may have direct psychopharmacological effects on
      conditioned cocaine craving.

PMID- 9543647
TI  - A family history and direct interview study of the familial aggregation of
      substance abuse: the adolescent substance abuse study.
AB  - The adolescent substance abuse (ASA) study collected information concerning drug
      use and psychopathology on male adolescent probands in treatment for substance
      abuse and also on matched control adolescents, as well as all available family
      members of both groups. Information was obtained through direct interview and the
      family history method of assessment. Both methods revealed greater alcohol and
      drug use, conduct disorder (CD) and antisocial personality disorder (ASP) in the
      relatives of treatment probands as compared with control relatives. These results
      suggest familial transmission, not only for alcohol abuse, but also for non
      alcohol substance abuse. Familial transmission for CD and ASP is also evident for
      both male and female relatives, although the prevalence of these disorders is
      significantly greater in males than females.

PMID- 9543648
TI  - Adolescent versus adult onset and the development of substance use disorders in
      males.
AB  - This study examines the influence of adolescent age of onset on the development
      of substance use disorders (SUD) by comparing adult males (n = 181) with SUD
      categorized into adolescent-onset, early-adult onset and late-adult onset groups
      on patterns of substance use and related disorders, time course of the
      development of substance dependence and rates of comorbid mental disorders. A
      sample of male adolescents (n = 81) with SUD was also included as a comparison
      group. The subjects were recruited from intervention programs in the community
      and participated in semistructured interviews with diagnoses determined by the
      best estimate method. Adolescent-onset adults, compared with other adult-onset
      groups, had higher lifetime rates of cannabis and hallucinogen use disorders,
      shorter times from first exposure to dependence, shorter times between the
      development of their first and second dependence diagnoses and higher rates of
      disruptive behavior disorders and major depression. Adolescents were similar to
      adolescent-onset adults. While the findings must be interpreted in light of
      methodological limitations, these results suggest that adolescent-onset SUD is a
      distinct subtype involving different substances and more rapid development than
      adult-onset SUD.

PMID- 9543649
TI  - The relationship of pre-treatment Alcoholics Anonymous affiliation with problem
      severity, social resources and treatment history.
AB  - Little research has examined the relationship of substance abuse patients' prior
      Alcoholics Anonymous (AA) affiliation to important treatment-related variables.
      This study of 927 individuals seeking treatment in public, health maintenance
      organization (HMO) and private-for-profit medical programs, found that 82.8% of
      patients presented at treatment with a history of AA affiliation. Degree of prior
      AA affiliation was significantly associated with more extensive prior utilization
      of formal and informal helping resources, current seeking of treatment in the
      public sector, having low income, being divorced/separated and having more severe
      alcohol, employment/support and psychiatric problems. Implications for service
      delivery and future research are discussed.

PMID- 9543650
TI  - Pharmacotherapy of cerebral ischemia in cocaine dependence.
AB  - This paper will examine how cerebral perfusion deficits in cocaine abusers may be
      a target for pharmacotherapy. The review covers five areas: (1) cerebral ischemia
      and neuropsychological impairment in cocaine abusers, (2) neuroimaging evidence
      for cerebral perfusion defects in cocaine abusers, (3) mechanisms for cocaine
      induced cerebral thrombosis, (4) neurotoxicity from cerebral ischemia and
      excitatory amino acids, (5) glutamate antagonists as potential treatment agents
      for cocaine induced neurotoxicity. Several pharmacotherapies are suggested
      including antiplatelet agents and excitatory amino acid (EAA) antagonists such as
      lamotrigine. Clinical trials in cocaine abusers with cerebral perfusion defects
      are indicated and EAA antagonists hold promise as they are developed for stroke
      treatment.

PMID- 9543651
TI  - International traffic in coca through the early 20th century.
AB  - This paper compiles records of coca exported by the major producing sites, Peru,
      Bolivia, Java and Formosa, from the late 19th century through the first third of
      the 20th century. During most of this era coca was legally produced and
      responsive to market demands. World coca exports did not peak [corrected] until
      around 1920, followed by a steady decline over the next decade. This export
      pattern (if not the exact figures) suggests a period of rising cocaine
      consumption, peaking regionally first in North America, then in Europe and other
      parts of the world, followed [corrected] by a marked decrease in the drug's
      popularity and acceptance.

PMID- 9543652
TI  - Self detoxication by amphetamine dependent patients: a pilot study.
AB  - Fifty current or past amphetamine dependent clients attending a Community Drug
      and Alcohol Team service took part in structured interviews about their previous
      attempts to stop using amphetamine. Thirty three had made a total of 47 attempts
      at self detoxication; 15 had undergone enforced withdrawal and ten had previously
      sought medical treatment. A total of 86% of subjects described significant
      withdrawal symptoms on stopping use of amphetamines. Increased use of other drugs
      was commonly reported as a means of coping with withdrawal, psycho-social
      techniques being used less systematically. The implications for the provision of
      attractive, effective treatments are discussed.

PMID- 9543653
TI  - Reliability of drug dependents' self-reports.

PMID- 9543654
TI  - Extending family therapy's horizons.

PMID- 9543655
TI  - Toward a developmentally informed narrative therapy.
AB  - Narrative approaches to psychotherapy emphasize the impact of the stories or
      narratives we construct on our reality and behavior. However, little effort has
      been made to elucidate how individuals' differential capacities for meaning
      making influence the process of re-storying lives. The present article introduces
      to family therapy a model of the changing nature of individuals' ability to
      create meaning. The model, referred to as developmental-constructivism (Kegan,
      1994), suggests that, in addition to contextual factors, individual differences
      in the capacity for organizing experience will influence therapeutic efforts to
      generate new and more adaptive narratives. The model is also presented as a
      heuristic for comparing and integrating two influential approaches to narrative
      therapy: the externalizing approach of Michael White and the solution-focused
      approach of Steve de Shazer.

PMID- 9543656
TI  - Hearing metaphor: an approach to working with family-generated metaphor.
AB  - This article presents a step-by-step approach to working with family-generated
      metaphor in family therapy. Although the use of therapist-generated "therapeutic
      metaphors" has been widely advocated and practiced for many years now, less
      attention has been paid to the metaphors used by family members. We argue that
      the family's metaphors are a neglected linguistic resource in family therapy.
      Highlighting and validating these metaphors produces a therapeutic conversation
      in which the voices of family members are heard more clearly by the therapist,
      and the families' own imaginative energies are engaged in defining and pursuing
      the goals of therapy. Several case examples illustrate the use of this approach
      with children of various ages.

PMID- 9543657
TI  - Family functioning and mental illness: a comparison of psychiatric and
      nonclinical families.
AB  - The primary objective of the present investigation was to examine adaptive
      functioning in the families of patients with a wide range of psychiatric
      disorders. Seven dimensions of family functioning, as measured by the Family
      Assessment Device (FAD), were compared across families of patients with a
      schizophrenia spectrum disorder (n = 61), bipolar disorder (n = 60), major
      depression (n = 111), anxiety disorder (n = 15), eating disorder (n = 26),
      substance abuse disorder (n = 48), and adjustment disorder (n = 46). Families in
      each psychiatric group were also compared to a control group of nonclinical
      families (N = 353). Results indicated that regardless of specific diagnosis,
      having a family member in an acute phase of a psychiatric illness was a risk
      factor for poor family functioning compared to the functioning of control
      families. However, with few exceptions, the type of the patient's psychiatric
      illness did not predict significant differences in family functioning. Thus,
      having a family member with a psychiatric illness is a general stressor for
      families, and family interventions should be considered for most patients who
      require a psychiatric hospitalization for either the onset of, or an acute
      exacerbation of, any psychiatric disorder.

PMID- 9543658
TI  - The Family Environment Scale: reliability and normative data for an adolescent
      sample.
AB  - The Family Environment Scale has been used extensively in family research since
      first being published. However, despite its appeal both conceptually and
      empirically, doubts have been raised over the scale's reliability. This article
      presents normative and reliability data for the Family Environment Scale from a
      large, combined sample of adolescents. Means and standard deviations were
      generally found to be in line with those reported in the scale's manual; however,
      estimates of internal consistency for most subscales could be considered
      inadequate for research purposes.

PMID- 9543659
TI  - Toward an African American genogram.
AB  - This article addresses the inadequacy of the standard genogram for African
      American families because of its underlying assumption that "family" is strictly
      a biological entity. The author suggests that this assumption is not culturally
      valid for African American families who have a long history of defining "family"
      as a kinship based on biological and functional ties. Using this
      conceptualization, an African American genogram is proposed.

PMID- 9543660
TI  - Marital interactions of male versus female alcoholics.
AB  - This study assessed the interactions of 131 alcoholic and nonalcoholic couples as
      they engaged in discussions of personally relevant problems. For 50 couples, the
      husband was alcoholic; for 15 couples, the wife was alcoholic; for 16 couples,
      both spouses were alcoholics; and for 50 couples, neither spouse was alcoholic.
      Observations were conducted during sessions when alcohol was consumed and in
      nondrinking sessions. Female alcoholic couples (with nonalcoholic spouses)
      demonstrated high negativity in the "no-drink" session, which was normalized in
      the drink session, suggesting an adaptive function to alcohol use. Concordant
      couples (both members were alcoholic) also demonstrated high negativity in the no
      drink session, but exhibited increased negativity in the drink session,
      suggesting that concordance has a maladaptive impact on marital interaction. All
      alcoholic groups demonstrated greater negativity and lower positivity and
      congeniality in their marital interactions compared to nonalcoholic couples.
      Couples with male alcoholics were the least divergent from normal control
      couples. Unique female patterns in alcoholism are discussed in terms of adaptive
      and reinforcing patterns and spousal influences.

PMID- 9543661
TI  - A prospective validation study of inclination, belief, and context predictors of
      family-focused prevention involvement.
AB  - Prior research by the authors tested a model of factors influencing parent
      inclination to participate in parenting interventions. Family context, belief,
      attitude, and inclination to participate variables from this model were used to
      predict the actual participation of 1,121 families in assessment and intervention
      activities of a family-focused preventive intervention research project.
      Invitations to the project assessment and intervention components were,
      respectively, about 6 months and 10 months following the initiation of a
      telephone survey collecting predictor variable data. Logistic regression analyses
      examining each predictor individually showed that a number of family context,
      belief, attitude, and inclination variables were predictive of project
      participation. Subsequently, multiple logistic regressions were conducted,
      entering variables by blocks corresponding to theoretical model components. These
      analyses showed that prospectively stated inclination to participate in a
      parenting intervention and level of education were consistently significant
      predictors of both assessment participation and intervention enrollment.
      Implications for both research and practice are discussed.

PMID- 9543662
TI  - Forbidden suffering: the Pollyanna syndrome of the disabled and their families.
AB  - Has suffering become an ugly word in the normalization debate? Are the disabled
      and their families forced into a Pollyanna culture in order to be acknowledged
      and accepted in good company as the worthy disabled? This essay poses a
      controversial question: I would like to start a debate and ask whether
      normalization also has an unseen, ideological downside.

PMID- 9543663
TI  - The meaning of disability and suffering: sociopolitical and ethical concerns.

PMID- 9543664
TI  - Optimizing immunohistochemistry: antigen retrieval and signal amplification.

PMID- 9543665
TI  - Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like
      differentiation (CASTLE) exhibits CD5 immunoreactivity: new evidence for thymic
      differentiation.
AB  - AIMS: Cases of intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus
      like differentiation (CASTLE) were examined for CD5 immunoreactivity, a feature
      of true thymic carcinoma, but not other thymic epithelial neoplasms or carcinomas
      of other sites. ITET/CASTLE, a rare, low-grade malignant neoplasm arising within
      the thyroid gland which resembles lymphoepithelioma-like and squamous cell
      carcinoma of the thymus, is postulated to arise from remnants of branchial pouch
      capable of thymic differentiation, but thymic differentiation in this neoplasm
      remains unproven. METHODS AND RESULTS: The largest published series of cases of
      ITET/CASTLE was examined for CD5 immunoreactivity using an anti-CD5 antibody
      reactive in fixed, paraffin-embedded tissue with microwave antigen retrieval.
      Neoplastic cells in all five cases of ITET/CASTLE studied were immunoreactive for
      CD5, including foci of tumour metastatic to lymph node and lung. In contrast,
      none of five cases of thyroid carcinoma with squamous differentiation was
      immunoreactive for CD5. A minority of cases of typical thyroid carcinomas showed
      some weak immunoreactivity for CD5. Other carcinomas of the head and neck were
      nonimmunoreactive for CD5. CONCLUSIONS: CD5 immunoreactivity in ITET/CASTLE is
      new evidence in support of thymic differentiation in this neoplasm.

PMID- 9543666
TI  - Anaplastic large cell malignant lymphoma with extensive eosinophilic or
      neutrophilic infiltration.
AB  - AIMS: We describe the clinicopathological features of eight cases of Ki-1
      positive anaplastic large cell malignant lymphoma (Ki-1 ALCL) in which there was
      extensive infiltration by eosinophils and/or neutrophils in the absence of
      necrosis. METHODS AND RESULTS: The patients comprised four males and four females
      with an age range of 24-74 years. Five cases had originally been diagnosed as
      Hodgkin's disease and one as true histiocytic lymphoma. In all cases, there was
      massive infiltration by eosinophils and/or neutrophils sometimes to such an
      extent that malignant cells were obscured. Immunohistochemical staining was
      performed using the monoclonal antibodies CD30, CD15, CD45, CD20, CD3, CD45RO,
      epithelial membrane antigen (EMA), CAM5.2, vimentin and CD68. In all cases,
      tumour cells were strongly positive for CD30 but negative for CD15. One case was
      positive for CD45 but none expressed B or T-cell markers. Five cases were
      positive for vimentin and two for EMA. Three of seven patients in whom adequate
      clinical details were available had stage III or IV disease at presentation and
      four exhibited B symptoms. Four patients had a peripheral neutrophilia and one a
      peripheral eosinophilia. CONCLUSIONS: The study shows that an eosinophil and/or
      neutrophil-rich variant of Ki-1 ALCD exists, expanding the morphological spectrum
      of this tumour.

PMID- 9543667
TI  - Multiple polypoid lesions of primary mucosa-associated lymphoid-tissue lymphoma
      of colon.
AB  - AIMS: This study was focused on unusual cases of mucosa-associated lymphoid
      tissue (MALT) lymphoma presenting with multiple polypoid lesions of the colon and
      rectum with a special reference to the differential diagnosis of mantle cell
      lymphoma. METHODS AND RESULTS: The lesions of these five cases grossly showed a
      segmental distribution of nodular protrusions in three patients and of
      innumerable small polyps in two. These patterns of involvement simulated those of
      multiple lymphomatous polyposis, known as the gastrointestinal presentation of
      mantle cell lymphoma (MCL), and caused a differential diagnostic problem between
      MALT lymphoma and MCL, which have different prognostic and therapeutic
      implications. Their histological features are almost indistinguishable from each
      other, especially in the small biopsy specimens via endoscope. The most important
      procedure for their differentiation is cyclin D1 immunohistochemistry and its
      negative reaction provides strong indication of MALT lymphoma. Of interest, one
      case showed a rare karyotypic abnormality of t(11;18)(q21;q21), which has been
      reported specifically in MALT lymphoma. CONCLUSIONS: This study has indicated
      that the multiple polypoid lesions of the colon occur not only in MCL, but also
      in MALT lymphoma, making differential diagnosis between the two entities
      necessary, and cyclin D1 immunohistochemistry is indispensable for distinguishing
      between them.

PMID- 9543668
TI  - Up-regulation of lysozyme production in colonic adenomas and adenocarcinomas.
AB  - AIMS: The presence of lysozyme protein in some gastric adenomas and
      adenocarcinomas has been well documented. There have been relatively few studies
      investigating the presence of lysozyme in tumours of the large intestine and they
      show contrasting results. We aim to investigate the cellular source and
      expression of lysozyme in colonic adenomas and adenocarcinomas. METHODS AND
      RESULTS: We randomly selected 29 and 27 colonic adenomas and adenocarcinomas,
      respectively. Using in-situ hybridization (ISH) and immunohistochemistry (IHC),
      we found an up-regulation of lysozyme in the dysplastic epithelium of all the
      adenomas studied, with more than 80% of cases expressing moderate to strong
      signals. Although the up-regulation of lysozyme was also observed in
      adenocarcinomas, only 30% of the cases showed moderate to strong signals, mostly
      with an uneven distribution. Down-regulation of lysozyme in the severely
      dysplastic and invasive foci were noted in some cases of adenoma with malignant
      transformation. Normal colonic glands were consistently negative for lysozyme at
      both the mRNA and the protein level, but inflamed and immature regenerative
      colonic epithelium at the crypt base showed positive signals in a similar pattern
      to those observed in the dysplastic epithelium of the adenomas. CONCLUSIONS: Our
      results confirm that colonic epithelium can produce lysozyme and its expression
      is up-regulated in the dysplastic epithelium in adenomas and in invasive cancer
      cells. It is interesting that regenerative colonic epithelium showed a similar
      pattern of lysozyme expression as in adenomas. The loss of lysozyme secreting
      phenotype in most of the invasive tumours suggests that lysozyme may not confer
      an advantage to tumour progression.

PMID- 9543670
TI  - Comparison of immunohistochemical staining of the novel antibody melan-A with
      S100 protein and HMB-45 in malignant melanoma and melanoma variants.
AB  - AIMS: The staining pattern of the recently described antibody melan-A was
      compared with those of S100 protein and HMB-45 in a variety of melanocytic
      lesions to assess the specificity and sensitivity of these antibodies. METHODS
      AND RESULTS: Immunohistochemical staining of paraffin sections of a range of
      melanocytic lesions was carried out following a high temperature antigen
      retrieval technique. The pattern and intensity of staining was semiquantitatively
      scored. S100 remains the most sensitive marker of melanocytic differentiation
      being diffusely positive in all benign and all primary and secondary malignant
      lesions including naevoid melanomas, and in most desmoplastic/spindle cell
      melanomas. Of the two more specific melanocytic markers melan-A stains the
      majority of benign and malignant lesions diffusely but with occasional patchy
      positivity only in some secondary melanoma deposits and with little staining of
      desmoplastic/spindle cell melanomas. HMB-45 is the least sensitive of the three
      showing little positivity of benign mature naevus cells, only variable patchy
      positivity of primary and secondary melanoma cells and limited positivity in
      naevoid, desmoplastic and metastatic melanomas. CONCLUSIONS: Melan-A is a useful
      addition to antibody panels as it is apparently specific for melanocytic lesions
      and is more sensitive than HMB-45; however, it has less value than S100 in the
      detection of spindle cell and desmoplastic melanomas.

PMID- 9543669
TI  - Expression of vascular endothelial growth factor in digestive neuroendocrine
      tumours.
AB  - AIMS: Angiogenesis is a complex multistep process essential for tumour growth.
      Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen
      and vascular permeability-inducing agent. Recent studies have shown that VEGF
      expression is correlated to microvessel density and tumour progression. The aim
      of this study was to analyse VEGF expression in a series of gastrointestinal
      neuroendocrine tumours. METHODS AND RESULTS: Surgical specimens from 28
      gastrointestinal carcinoids and 20 pancreatic endocrine tumours were examined for
      VEGF expression by immunohistochemistry. Intense cytoplasmic staining for VEGF
      was observed in several cells of the islets of Langerhans and in neuroendocrine
      cells of normal digestive mucosa. All midgut carcinoids showed strong VEGF
      expression in tumoral cells. Positive VEGF immunostaining was observed in 16 of
      20 neuroendocrine pancreatic tumours but it was usually much lower than in midgut
      carcinoids. Western blotting analysis in eight cases identified a major band at
      30-32 kDa. No correlation between VEGF expression and tumour stage was found.
      CONCLUSIONS: This study demonstrates that neuroendocrine cells are a major source
      of VEGF, particularly in midgut carcinoids. This finding suggests that the
      presence of VEGF may be required to maintain the differentiated state of
      capillary vessels in these hypervascular tumours. Such secretion, in conjunction
      with the other growth factors synthesized by these neuroendocrine tumours, may
      have an important role in tumour growth.

PMID- 9543671
TI  - Spontaneous regression of hepatocellular carcinoma.
AB  - AIMS: To determine the clinical and histopathological features of a case of a
      spontaneous regression of hepatocellular carcinoma (HCC). CASE DETAILS: HCC was
      found incidentally in a 73-year-old man during a laparotomy for evaluation of
      gastric retention. Despite no treatment being given, he improved gradually with
      no sign of tumour as evidenced by coeliac angiography 15 months later, as well as
      by explorative laparotomy after another 2 years. The patient died 15 years after
      the primary diagnosis of HCC, without known evidence of tumour recurrence. The
      patient's clinical records were reviewed, and paraffin-embedded liver tissue was
      re-evaluated. Both histological and immunohistochemical features were compatible
      with the diagnosis of a well differentiated HCC. Conceivable causes of the
      spontaneous regression of this and other reported cases are discussed, but the
      phenomenon remains enigmatic. CONCLUSIONS: This case with a histologically proven
      HCC and a very long follow-up time confirms that spontaneous regression does
      occur. Since the case was found incidentally our report also implies that this
      may not be as rare as reported.

PMID- 9543672
TI  - Analysis of CD44 expression in serous and mucinous borderline tumours of the
      ovary: comparison with cystadenomas and overt carcinomas.
AB  - AIMS: To determine the diagnostic and prognostic value of the immunohistochemical
      analysis of CD44 variants in benign borderline and malignant tumours of the
      ovary. METHODS AND RESULTS: The reactivity of tumour cells with three monoclonal
      antibodies, respectively, directed to all CD44 variants, CD44-v3 isoform and CD44
      v6 isoform, was assessed by using an indirect immunoperoxidase technique applied
      to formalin-fixed, paraffin-embedded samples of 36 cases of borderline, as
      compared to 20 cases of benign tumours and 20 cases of carcinomas. CD44 variants
      were detected in 97% of borderline tumours, as compared to 60% of benign tumours
      and 100% of carcinomas. CD44-v3 was detected in 25% of borderline tumours, as
      compared to 0% of benign tumours (P = 0.003) and 55% of carcinomas (P = 0.065).
      The expression of CD44-v6 was detected in 28% of borderline tumours, as compared
      to 20% of benign tumours and 30% of carcinomas. In borderline tumours, as in
      carcinomas, CD44-v6, but not CD44-v3, expression was correlated with an increased
      proliferative index and with a higher incidence of p53 expression. CONCLUSION:
      Borderline tumours of the ovary present frequent quantitative and qualitative
      alterations in the pattern of expression of CD44 proteins. However, these
      alterations are unlikely to represent useful diagnostic or prognostic markers.

PMID- 9543673
TI  - Dissecting leiomyoma of the uterus with extrauterine extension.
AB  - AIMS: Familiarity with benign uterine smooth muscle tumours with unusual growth
      patterns by gynaecologists and pathologists is essential in avoiding misdiagnosis
      and overtreatment. CASE DETAILS: An enlarged uterus in a 35-year-old woman
      contained numerous, ill-defined nodules with marked hydropic changes which showed
      an extrauterine extension. Histologically, although some nodules had an
      appearance of conventional leiomyoma, the predominant part of the lesion was
      characterized by ill-defined spindle cell nodules with marked hydropic changes
      and irregular dissection of the myometrium. The cellularity was variable from
      area to area and there were neither nuclear atypia nor mitotic figures. No
      coagulative tumour necrosis was observed. The extrauterine components, which were
      in continuity with the intrauterine nodule, were histologically identical to the
      intrauterine nodules except for the complication of endometriosis.
      Immunohistochemically, the tumour cells were positive for vimentin, desmin, alpha
      smooth muscle actin and muscle actin (HHF35). The tumour was DNA diploid by flow
      cytometry. The patient was well and without disease 6 months after hysterectomy.
      CONCLUSIONS: This tumour illustrates that rare benign smooth muscle tumours can
      proliferate in dissecting and extrauterine growth patterns, findings that should
      not be confused with malignant mesenchymal tumours.

PMID- 9543674
TI  - Solid alveolar rhabdomyosarcoma of the thorax in a child.
AB  - AIMS: This case illustrates the difficulties and pitfalls of diagnosis of
      alveolar rhabdomyosarcoma in its solid variant and in an unusual primary
      location, the mediastinum. CASE DETAILS: A 9-year-old boy presented with a
      primary thoracic tumour associated with metastasis in the left sacroiliac joint.
      Bronchial and mediastinal biopsies showed a malignant neoplasm with a solid sheet
      like pattern of small round cells with a high nuclear to cytoplasmic ratio
      associated with little or no fibrosis usually evocative of a peripheral
      neuroectodermal tumour (PNET) at this age. Immunohistochemical positive staining
      with vimentin (80% of tumour cells), desmin (20%) and titin (30%) antibodies was
      suggestive of a rhabdomyosarcoma. In addition, all neural cell adhesion molecule
      (NCAM) markers tested were positive as well as MIC2, a marker for the Ewing
      family of sarcomas. There was no rhabdomyoid differentiation at ultrastructural
      examination. Molecular analysis with RT-PCR amplification of RNA isolated from
      the tumour demonstrated the presence of a PAX3/FKHR fusion transcript, product of
      a t(2;13) reciprocal translocation, a genetic marker specific for alveolar
      rhabdomyosarcoma. CONCLUSIONS: The diagnostic methodology of a small round cell
      tumour of the child must now include immunohistochemical study and molecular
      biology to confirm the diagnosis of alveolar rhabdomyosarcoma, in a solid and
      undifferentiated variant.

PMID- 9543675
TI  - Pathology of the spleen: report on the workshop of the VIIIth meeting of the
      European Association for Haematopathology, Paris 1996.

PMID- 9543676
TI  - Langerhans cell histiocytosis associated with papillary carcinoma of the thyroid.

PMID- 9543677
TI  - Multinodular pleural involvement in aggressive systemic mast cell disease.

PMID- 9543678
TI  - Ovarian atypical endometriosis.

PMID- 9543679
TI  - Pilomatrixoma of the ovary: a rare variant of mature teratoma.

PMID- 9543680
TI  - Prostate specific antigen and the salivary gland.

PMID- 9543682
TI  - Pituitary corticotroph adenoma in a primary enlarged empty sella turcica.

PMID- 9543681
TI  - Monophasic sarcomatoid carcinoma of the breast.

PMID- 9543685
TI  - Metabolic and membrane-altering toxins, molecular differentiation factors, and
      pheromones in the evolution and operation of endocrine-signalling systems.
AB  - The endocrine systems of vertebrates and higher invertebrates may have evolved
      functionally from as far back on the evolutionary scale as bacteria and early
      multicellular organisms and their biological communities, which have been shown
      to produce a variety of cyclic nucleotides, peptides, fatty acids, prostaglandins
      and sterols with endocrine-altering effects in primative as well as more highly
      evolved species.

PMID- 9543683
TI  - Giant cell angiofibroma of the mediastinum.

PMID- 9543684
TI  - Enhancement of apoptotic susceptibility in human endometrial epithelial cell line
      HHUA by transforming growth factor-beta 1.
AB  - Although reports have been published on the generation of transforming growth
      factor-beta 1 (TGF-beta 1) and expression of TGF-beta receptors in human
      endometrial tissues, the biological functions of endometrial TGF-beta 1 have
      remained unclear. In this study, the effects of TGF-beta 1 on endometrial
      apoptosis were examined by using an endometrial epithelial cell line HHUA which
      is susceptible to Fas-mediated apoptosis. TGF-beta 1 alone did not affect the
      cell growth of HHUA, but pretreatment of HHUA with TGF-beta 1 enhanced Fas
      mediated growth suppression and DNA fragmentation of the cells. Flow cytometric
      analyses showed that TGF-beta 1 did not affect Fas expression on the cell
      surface. These findings lead to the conclusion that TGF-beta 1 enhances
      susceptibility to Fas-mediated apoptosis in the endometrial epithelial cell.
      Modulation of Fas-mediated endometrial apoptosis by TGF-beta 1 may thus be a
      tissue-specific effect which is distinct from other TGF-beta 1 effects on Fas
      mediated apoptosis in activated T-cells and rheumatoid synovial cells. The
      biological functions of endometrial TGF-beta 1 and endometrial apoptosis are also
      discussed.

PMID- 9543686
TI  - Effect of insulin on intramuscular 3-hydroxybutyrate levels in diabetic rats.
AB  - It has been shown that inhibition of lipolysis and ketogenesis by insulin is more
      sensitive than suppression of hepatic glucose production and stimulation of
      tissue glucose uptake. Clinically, on the other hand, blood glucose
      concentrations fall much more quickly than blood ketone concentrations.
      Therefore, during continuous insulin infusion at a rate of 3.0 mU/kg B.W./min
      over a period of 150 min we monitored blood glucose and 3-hydroxybutyrate (3
      OHBA) concentrations and muscle 3-OHBA levels using the microdialysis technique
      in streptozotocin-induced diabetic rats. Blood glucose concentrations decreased
      rapidly after insulin infusion. However, significant reduction in blood-3-OHBA
      concentration was found for the last 30 min. In muscle dialysate 3-OHBA
      concentrations and muscle local blood flow there was no significant change
      throughout the study. These results suggest that one possible mechanism of
      delayed improvement in ketonemia is a reduction in muscle removal capacity.

PMID- 9543687
TI  - Type II diabetics with macrovascular complications: polymorphonuclear leukocyte
      (PMN) filtration, PMN membrane fluidity and cytosolic Ca2+ content after
      activation.
AB  - We evaluated polymorphonuclear (PMN) filtration parameters, membrane fluidity and
      cytosolic Ca2+ content in 21 normal subjects and in 18 type II diabetics with
      macrovascular complications (MVC). Evaluations were carried out at baseline and
      after in vitro activation prolonged for 5 and 15 min. PMA (4-phorbol 12-myristate
      13-acetate) and fMLP (N-formyl-methionyl-leucyl-phenylalanine) were used as
      stimulating agents. TMA-DPH (1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5
      hexatriene) was used as fluorescent probe for the membrane fluidity tests and
      Fura 2-AM for the cytosolic Ca2+ content. A significant variation was evident in
      PMN filtration parameters at 5 and 15 min. No variation was present in PMN
      membrane fluidity and cytosolic Ca2+ content in normals. In type II diabetics
      with MVC, we found an increase solely in PMN cytosolic Ca2+ content after PMA
      activation and an early decrease in PMN membrane fluidity and a late increase in
      PMN cytosolic Ca2+ content after fMLP activation. After PMA activation alone (at
      15 min), PMN filtration distinguishes normals from type II diabetics with MVC.
      The PMN filtration parameters behave similarly in the two groups, but PMN
      membrane fluidity and cytosolic Ca2+ content behave differently.

PMID- 9543688
TI  - Ay-4166 increases the sensitivity of insulin secretion to glucose in isolated
      perfused rat pancreas.
AB  - To study the effect of a therapeutic dose (3 microM) of AY-4166 on the glucose
      stimulated insulin secretion, the rat pancreas was perfused with 5 to 15 mM
      glucose. AY-4166 did not affect the basal insulin secretion at 5 mM glucose, and
      increased the first and second phases of insulin secretion stimulated by 7.5 to
      15 mM glucose. The dose-response curve of the insulin secretion to glucose was
      shifted to the left side by AY-4166. These results suggest that AY-4166 ist not a
      stimulator releasing insulin independently of glucose concentrations, but a
      potentiator of insulin secretion.

PMID- 9543689
TI  - Fatty acids inhibit adrenocorticotropin-induced adrenal steroidogenesis.
AB  - Unsaturated long chain fatty acids modulate hormone secretion from a variety of
      endocrine glands, including the adrenal cortex. Oleic acid and linoleic acid have
      been shown to stimulate production of glucocorticoids in the absence of
      adrenocorticotropic hormone, but at a high concentration appeared to inhibit the
      action of this hormone. In the present study, the concentration dependence of the
      inhibitory actions of these two fatty acids was tested in collagenase-dispersed
      rat adrenal fasciculata cells, and the effects of both lipids on cAMP production
      were also determined. Adrenocorticotropic hormone stimulated steroid production
      from isolated cells approximately ten-fold above unstimulated cells. Oleic and
      linoleic acid significantly inhibited the response to this hormone by 44% and
      54%, respectively. The half-maximally effective inhibitory concentration of both
      lipids was between 75-100 microM. A maximal concentration of adrenocorticotropic
      hormone increased cAMP secretion 138-fold above unstimulated cells. Oleic and
      linoleic acids inhibited the increase in cAMP secretion by 47% and 33%,
      respectively. It is concluded that pathophysiological concentrations of
      unsaturated fatty acids inhibit the action of adrenocorticotropic hormone on the
      adrenal gland, and that the mechanism of action of the lipids may be partly via
      inhibition of cAMP production.

PMID- 9543690
TI  - Ovariectomy fails to modify the cardiac myosin isoenzyme profile of adult rats.
AB  - Estrogen has been shown to help maintain the elevated expression of the high
      ATPase myosin isoform, V1, present in the hearts of young rats (< 70 days of
      age). Because hearts of this age are still undergoing significant maturation, the
      current study sought to determine if estrogen similarly regulates myosin
      isoenzyme expression in the mature adult heart. To make this determination, ten
      month old retired female Sprague-Dawley rats were made estrogen-deficient by
      ovariectomy (OVAR, n = 8). Sham-operated (CONTR, n = 8) animals served as
      controls. Nine weeks later, the animals were sacrificed and left ventricular
      tissue collected. Crude myofibrills were isolated from these samples and
      electrophoretically separated into the three isoenzymatic forms of cardiac myosin
      (V1, V2, and V3). OVAR animals were larger than the CONTR group (p < 0.05), but
      heart weight/body weight ratios were not different between groups. Distribution
      of myosin among its three isoenzymes was similar between groups (CONTR: V1, 80%,
      V2, 14%; V3, 6%; OVAR: V1, 77%, V2, 16%, V3, 7%). These data demonstrate that
      myosin isoenzyme distribution in the adult heart is unaltered by ovariectomy,
      suggesting that estrogen loses its ability to regulate expression of this protein
      in the mature heart.

PMID- 9543691
TI  - Parathyroid hormone activity increases during endotoxemia in conscious rats.
AB  - Our previous studies showed that the phosphaturic effect of parathyroid hormone
      (PTH) is blunted during acute-phase endotoxemia in anesthetized rats. However,
      the possibility that the antiphosphaturia was secondary to hyponatriuresis due to
      endotoxin (Et)-induced acute renal failure could not be ruled out. The objective
      of this study was to evaluate phosphate (Pi) excretion during early- and late
      phase endotoxemia in conscious rats fed by total parenteral nutrition. Male
      Wistar rats weighing 270 g were used. Urine samples were taken to determine the
      Pi excretion rate for 12 h just after Et (E. coli B055) challenge (early-phase
      endotoxemia), and for 12 h after a 36-h recovery period following Et challenge
      (late-phase endotoxemia). Rats given isovolumetric saline instead of Et served as
      controls. Et injection reduced endogenous creatinine clearance markedly (0.88 +/-
      0.12 ml/min, P < 0.0001, n = 7) and caused hyponatriuresis (0.80 +/- 0.19
      microliters/min, P < 0.001) compared with saline injection (1.78 +/- 0.10 ml/min
      and 3.12 +/- 0.39 microliters/min, respectively, n = 8) during the early phase.
      Greater phosphaturia and hypocalciuria were observed simultaneously during early-
      (Pi excretion = 4.18 +/- 1.38 micrograms/min, P < 0.05; calcium excretion = 0.70
      +/- 0.14 micrograms/min, P < 0.05) and late-phase (4.76 +/- 1.72 micrograms/min,
      P < 0.05; 0.60 +/- 0.18 micrograms/min, P < 0.05, respectively) endotoxemia (n =
      8) in comparison with the respective control values (1.61 +/- 0.39 and 1.40 +/-
      0.21 micrograms/min, early; 0.34 +/- 0.14 and 1.97 +/- 0.55 micrograms/min, late,
      n = 6). Et adminidstration resulted in a significantly increased plasma PTH
      concentration during the late phase (34.7 +/- 7.0 pg/ml, P < 0.05) compared with
      saline administration (15.4 +/- 2.4 pg/ml). In conclusion, these data suggest
      that the hyperphosphaturia during endotoxemia lasting longer than 12 h is
      attributable to elevated PTH secretion.

PMID- 9543692
TI  - Intravenous methylprednisolone pulse therapy in the treatment of Graves'
      ophthalmopathy.
AB  - Graves' ophthalmopathy (GO) is a specific immune-mediated disorder, whose
      treatment is sometimes difficult. In order to investigate the efficacy of
      intravenous methylprednisolone (MP) pulse therapy in GO, we studied eight
      patients with GO, followed up for at least 6 months by clinical patient self
      assessment, ophthalmological examination and orbital computed tomography (OCT). A
      12.5 mg/kg dose of MP was administered intravenously over a 10 hour period, once
      every month. Three to six MP pulse administrations were performed in each
      patient. All patients were outpatients. A 0.5 mg/kg/day oral prednisone dose was
      given to each patient as interpulse therapy. Clinical assessment of MP pulse
      therapy showed a good response in 87.5% and no response in 12.5% of patients. The
      treatment was rapidly efficient, mostly on patient self-assessment, soft tissue
      inflammation, ophthalmoplegia, corneal involvement, visual acuity and extraocular
      muscle enlargement on OCT. Post-treatment ophthalmic index was significantly
      improved (6.75 +/- 3.06 vs. 2.5 +/- 1.41: p < 0.05). MP pulse therapy had less
      effect on proptosis (22.94 +/- 2.32 mm vs. 21.56 +/- 2.22 mm: p < 0.05). No
      adverse effects were noted with MP pulse therapy. Patients showed no relapse of
      eye involvement during a mean follow up of 31.8 months (2-77 months). In
      conclusion, our results suggest that intravenous MP pulse therapy is a good
      immunosuppressive therapy for GO. Moreover, in comparison with the previous
      studies, the MP dose used in our present study appears to be optimal with high
      efficacy. MP pulse therapy represents a safe and efficient treatment in GO, which
      can easily be performed in outpatients.

PMID- 9543693
TI  - Intracellular magnesium depletion relates to increased urinary magnesium loss in
      type I diabetes.
AB  - We investigated whether erythrocyte magnesium (Mg) depletion exists in subjects
      with Type I diabetes. To this end, Mg levels in plasma, erythrocytes and urine
      were determined in 12 patients with Type I diabetes and compared with 12 healthy
      control subjects. Mean plasma Mg concentrations were comparable between diabetic
      patients and control subjects (0.90 +/- 0.29 mmol/l vs 1.04 +/- 0.14 mmol/l,
      respectively; p = 0.16). Mean erythrocyte Mg concentration was significantly
      lower in the diabetic group compared with the control group (1.41 +/- 0.56 mmol/l
      vs. 2.94 +/- 1.13 mmol/l, respectively; p < 0.0001). Mean urine Mg excretion was
      significantly elevated in the diabetic group with respect to the controls (6.86
      +/- 3.5 mmol/g creatinine/24 h vs. 4.03 +/- 1.65 mmol/g creatinine/24 h,
      respectively; p = 0.02). As to the diabetic group, erythrocyte Mg concentration
      showed a significant inverse correlation with urine Mg excretion (r = -0.58, p =
      0.049). There was no correlation between urine Mg concentration and glycosylated
      hemoglobin or fasting plasma glucose level. The data suggest that intracellular
      Mg depletion without significant hypomagnesemia is related to increased urinary
      Mg loss in patients with Type I diabetes. The urinary Mg loss is not correlated
      with the degree of metabolic control.

PMID- 9543694
TI  - Circulating levels of 7 S domain of type IV collagen and atrial natriuretic
      peptide in normotensive type 2 diabetic patients with or without retinopathy.
AB  - Thickening of the basement membrane and other structural alterations of the
      vascular walls occur frequently in patients with diabetes. The vascular response
      to atrial natriuretic peptide (ANP) is also altered in these patients. Abnormal
      vascular response in diabetes may be due to alteration of vascular
      physicochemical properties induced by accumulation of components of vascular
      basement membrane. The aim of this study was to evaluate the relationship between
      circulating levels of the 7 S domain of type IV collagen (7 S-collagen), and ANP
      in normotensive type 2 diabetic patients with or without retinopathy. Forty-one
      normotensive type 2 diabetic patients (n = 19 with and n = 22 without
      retinopathy) and 18 age-matched control subjects participated in the study. Serum
      7 S-collagen and plasma ANP levels were measured by radioimmunoassays. Serum 7 S
      collagen (4.4 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01) levels and plasma ANP (20.8
      +/- 1.0 vs 15.5 +/- 1.0 pg/ml; p < 0.01) were significantly higher in diabetic
      patients than in normal subjects. Serum 7 S-collagen increased significantly in
      diabetic patients without retinopathy compared with normal subjects (4.1 +/- 0.1
      vs 3.5 +/- 0.1 ng/ml; p < 0.01). Diabetic patients with retinopathy showed
      significantly higher circulating concentrations of 7 S-collagen (4.6 +/- 0.1 vs
      4.1 +/- 0.1 ng/ml; p < 0.01) and ANP (22.9 +/- 1.4 vs 18.9 +/- 1.3 pg/ml; p <
      0.05) than those without retinopathy. There was a significant and positive
      correlation (r = 0.51, p < 0.01) between the circulating levels of 7 S-collagen
      and ANP in all patients. The results of this investigation showed that increased
      circulating levels of ANP correlate with the abnormal metabolism of the vascular
      basement membrane observed in diabetic patients with microangiopathy.

PMID- 9543695
TI  - In most poorly controlled glyburide-treated type 2 diabetic patients drug
      withdrawal causes further increase in glycemia not accompanied by changes in
      insulin secretion.
AB  - To find out whether the secondary failure of glyburide in type 2 diabetes is
      complete or partial, we studied 38 patients, age (M +/- SD) 69 +/- 9 years,
      suffering from diabetes from 13.5 +/- 8.4 years and treated with glyburide for 5
      13 years, with poor glycemic control (glycohemoglobin 10.6 +/- 2.6%). Serum
      glucose, insulin and C-peptide were assayed before and 1 h and 2 h after a
      simulated meal load (355 Cal), after which the drug was replaced with placebo for
      4 weeks, and the test repeated. After glyburide withdrawal, fasting glycemia
      increased from 10.3 +/- 3.3 to 15.1 +/- 4.4 mmol/L (p < 0.001), but in 3/38
      patients, it even decreased and in five others the changes were less than +/- 2
      mmol/L. These changes negatively but only weakly correlated with initial
      glycemia: r = 0.4123, p < 0.010. The mean post-meal glycemia at 1 h and 2 h
      increased respectively by 3.3 and 5.9 mmol/L (both p < 0.001). Neither the levels
      of glycemia nor its changes after the glyburide withdrawal correlated with the
      levels of, or changes in, insulin or C-peptide. We conclude that in most but not
      all type-2 diabetic patients, poorly controlled with glyburide, the drug still
      retains some limited therapeutic effectiveness, and therefore its withdrawal
      causes further deterioration of control with the almost equal increases in
      fasting and post-meal levels of glycemia. These changes are not accompanied by
      decrease in insulin secretion.

PMID- 9543696
TI  - Soluble (s) CD14 and plasmatic lipopolysaccharides (LPS) in patients with chronic
      hepatitis C before and after treatment with interferon (IFN)-alpha.
AB  - CDI4 is a monocyte/polymorphonuclear cell receptor for lipopolysaccharide (LPS)
      LPS Binding Protein (LBP), which mediates most of the toxic effects exerted by
      such a bacterial component in the host. Here, we provide evidence that sCD14 and
      interferon (IFN)-gamma serum levels are significantly higher in chronic hepatitis
      C (CH-C) patients than those detected in normal donors. On the other hand,
      CD4+/CD8+ antibacterial activity is depressed, thus facilitating entry of
      bacteria into the host. Of note, all these immune parameters are not modified by
      in vivo IFN-alpha administration over a period of one year. Finally, after 12
      months of IFN-alpha treatment number of CH-C patients with detectable levels of
      plasmatic LPS increased, thus indicating a continuous release of LPS into the
      host and also suggesting a putative pathogenetic role for sCD14 LPS-LBP complex
      in subjects affected by CH-C virus infection.

PMID- 9543698
TI  - Enhancing and priming of macrophages for superoxide anion production by taxol.
AB  - Taxol, an anticancer drug, has been known not only to block cell division by
      stabilizing microtubules but also to activate murine macrophages to express TNF
      alpha, interleukin-1, and to produce nitric oxide (NO). We therefore reasoned
      that taxol could activate murine macrophages to generate reactive oxygen
      intermediates, such as superoxide anion (O2-), which are responsible for
      intracellular killing of pathogenic microbes. Treatment of RAW264.7 cells, murine
      macrophage cell line, with taxol increased phorbol ester-induced O2- production
      in a dose dependent manner (approximately 2 fold). In addition, taxol rapidly (<
      1 hr) primed RAW264.7 cells to enhance O2- release stimulated with PMA. Taxol
      also enhanced stimulation of O2- production by FMLP, but not by Con A. This
      effect was abolished by prior treatment with both superoxide dismutase (SOD) and
      N-acetyl-L-cystein, a free radical scavenger. To investigate the mechanism of
      taxol-induced macrophage stimulation, we evaluated the ability of colchicine, a
      drug that inhibit tubulin polymerization, and cAMP analogues, which is known to
      depolymerize microtubule. Taxol-induced O2- production was inhibited by the
      treatment with both colchicine and DB-cAMP. Taken together, these results
      demonstrated that taxol provides two signals, "priming" and "enhancing", to
      generate superoxide anion via the stabilization of microtubules in murine
      RAW264.7 cells

PMID- 9543697
TI  - Tumor regression of advanced carcinomas following intra- and/or peri-tumoral
      inoculation with VRCTC-310 in humans: preliminary report of two cases.
AB  - The authors report their clinical experience with VRCTC-310 in two patients
      suffering with advanced cancer in which the skin was severely compromised. VRCTC
      310 is a combination of the snake venoms crotoxin (CT) and cardiotoxin (CD). The
      local (peritumoral) treatment with the drug (0.O14 mg/kg/week during 6 weeks)
      provoked the complete disappearance of a relapsed skin squamous cell cancer in
      one patient. The other patient was an aged woman with local-advanced breast
      cancer (carcinoma en cuirasse) who was inoculated intra-and-peritumoral with
      VRCTC-310. After 6 weekly courses (0.014 mg/kg/week) with the drug a > 80% tumor
      reduction was seen. A 133 days follow-up demonstrated not only an objective
      complete response of the primary tumor mass, but the disappearance of
      supraclavicular tumor mass as well a significant reduction in lymphangitis. To
      our knowledge, this is the first communication about the in vivo antitumoral
      activity of VRCTC-310 when injected locally to humans. Further studies are now in
      progress.

PMID- 9543699
TI  - Effect of propranolol and IFN-beta on the induction of MHC class II expression
      and cytokine production by IFN-gamma IN THP-1 human monocytic cells.
AB  - This study was undertaken to investigate the effects of propranolol, IFN-beta,
      and the protein kinase modulators on IFN-gamma induction of MHC class II antigen
      expression and cytokine production in THP-1 human monocytic cells. IFN-gamma
      induced expression of HLA-DR and DQ molecules and secretion of the monokines IL-1
      beta and TNF-alpha in THP-1 cells in a time and dose-dependent manner. The effect
      of INF-gamma on class II HLA antigens was dose-dependently inhibited by IFN-beta.
      H-7, phloretin, staurosporine as well as GF 109203X are selective enzyme
      inhibitors of protein kinase C (PKC), down-regulating IFN-gamma induced MHC class
      II expression and cytokine production. Stimulators of PKC, like PMA, replaced IFN
      gamma in the induction of monokines in THP-1 cells, whereas the addition of HA
      1004 or arachidonic acid to the culture had no effect on IFN-gamma mediated
      changes. Blocking of phospholipase D (PLD)-derived diacylglycerol (DAG) formation
      by propranolol abrogated IFN-gamma increased HLA class II expression and IL-1
      beta secretion, but had little effect on IFN-gamma induced TNF-alpha production.
      These findings appear to suggest that PLD-derived phosphatidate is not the
      primary source of DAG production in IFN-gamma-induced TNF-alpha secretion, but
      may be necessary for IFN-gamma-mediated MHC class II induction and IL-1 beta
      production in human monocytes, whereas phospholipase A2 may not be required for
      IFN-gamma activation of PKC in the process.

PMID- 9543700
TI  - Effects of 2-chlorodeoxyadenosine and gold sodium thiomalate on human bcl-2 gene
      expression.
AB  - Aberrant expression of apoptosis-related genes, including the "cell death
      suppressor gene" bcl-2, may play an important pathogenetic role in cancer and
      autoimmune diseases, In vivo upregulation of bcl-2 mRNA in synovial lining cells
      of patients with rheumatoid arthritis but not in patients with osteoarthritis has
      been recently found. In the present study we investigated whether agents exerting
      beneficial effects in patients with rheumatoid arthritis, namely the long used
      Gold Sodium Thiomalate (GST) and the novel immunosuppressive, purine analogue 2
      chlorodeoxyadenosine (2-CdA), a lymphocyte apoptosis-inducing agent interfere
      directly with induction of bcl-2 mRNA expression. The phytohemagglutinin (PHA)
      induced in vitro proliferation of normal human peripheral blood lymphocytes was
      significantly inhibited by non-toxic concentrations of 2-CdA and GST which are
      within the range of in vivo plasma concentrations in patients receiving the
      respective treatment. Using mRNA dot-blot analysis and hybridization with an IL-2
      specific probe we found that GST, similarly to dexamethasone that served as
      control, suppressed the PHA-induced IL-2 mRNA accumulation dose-dependently. In
      contrast, 2-CdA (0.1 microgram/ml) at concentrations that inhibit by 80-90% the
      PHA-induced proliferative responses of lymphocytes did not affect IL-2 mRNA
      accumulation. Hybridization with a bcl-2-specific probe showed that the
      activation-induced accumulation and kinetics of bcl-2 mRNA were not changed in
      the presence of a wide range of concentrations of either GST or 2-CdA. Similarly,
      the mRNA accumulation of the "house-keeping" control gene beta-action remained
      unchanged by both agents. These findings indicate that biosynthesis of bcl-2 is
      not specifically affected by GST and CdA, suggesting that the immunomodulating
      effects of these agents, including their efficacy in suppressing chronic
      arthritis, are not related with a bcl-2-dependent mechanism.

PMID- 9543701
TI  - Effect of macrophage colony-stimulating factor (M-CSF) on mouse immune responses
      in vivo.
AB  - We examined the effects of recombinant human M-CSF (rhM-CSF) on mouse macrophages
      and immune responses in vivo. Intraperitoneal administration of rhM-CSF (20-500
      microgram/ml) increased Mac-1+ cell numbers in the peritoneal cavity. The
      tumoricidal activities of the macrophages from vehicle-administered (V-M phi) and
      from rhM-CSF-administered (M-M phi) mice were the same as those observed in
      vitro. However, when activated by lipopolysaccharide (LPS), the tumoricidal
      activity of M-M phi was stronger than that of V-M phi. Intravenous administration
      of rhM-CSF (500 micrograms/gk) increased the number of spleen cells. Flow
      cytometric analysis showed that administration of rhM-CSF increased Mac-1+, B220+
      and NK 1.1+ cell counts in the spleen. However, CD4+ and CD8+ cell numbers did
      not change. Concomitant increases were observed in levels of IL-4 and IL-10 in
      mouse serum following rhM-CSF administration, but no significant changes were
      observed in the serum level of IFN-gamma. In experiments involving mouse immune
      responses, the administration of rhM-CSF reduced the contact sensitivity (CS)
      reaction against picryl chloride (PC) and augmented IgE production in response to
      2,4-dinitrophenyl (DNP), but did not affect the production of either IgM or IgC1.
      These results suggest that administration of rhM-CSF not only activates murine
      macrophages, but modulates antigen-specific immune responses in vivo.

PMID- 9543702
TI  - Hydrogen peroxide modulation of the superoxide anion production by stimulated
      neutrophils.
AB  - Hydrogen peroxide (H2O2) pretreatment of human neutrophils results in a
      suppression of the superoxide anion (O2) production in response to surface-acting
      stimulants such as lipopolysaccharide (LPS) and opsonized zymosan. This effect
      was not observed when phorbol myristate acetate (PMA), formyl-methionyl-leucyl
      phenylalanine (fMLP) or tumor necrosis factor alpha (TNF alpha) were used as a
      stimuli. Since the response to PMA and other stimuli was unimpaired by
      preincubation with H2O2, we assume that the H2O2 modulated O2 production is
      probably due to alteration of the LPS receptor conformation rather than effecting
      directly NADPH-oxidase. The balance of reactive oxygen species (ROS) produced by
      neutrophils in the state of sepsis may thus be autoregulated by negative feedback
      phenomena of locally produced H202.

PMID- 9543703
TI  - Immunostimulatory activity of Milife, a novel immunomodulator of fungus origin.
AB  - Milife is a novel immunomodulator derived from the fungus Fusarium Sambucium. In
      this study we examined immunomodulatory properties of Milife in 10 months-old
      BLRB mice. Milife was given to mice orally in a daily dose of 1 mg per mouse, for
      2 to 6 days. Groups of mice were sacrificed on days 2, 4, and 6 of treatment, and
      3 weeks after completion of a 6 days treatment with Milife, and lymphoid organs
      were obtained for analysis. Milife administration led to rapid and significant
      increase in total leukocyte and lymphocyte numbers in peripheral blood that
      persisted for at least 3 weeks after a 6 days treatment. Cellularity of lymph
      nodes, bone marrow and thymus increased significantly at days 4 and 6 of
      treatment, but returned to pretreatment levels after Milife discontinuation.
      Though total splenocyte numbers did not change dramatically, there occurred
      delayed increase in CD4+ cells in the spleen 3 weeks following treatment.
      Preferential accumulation of CD4+ cells was also consistently found in peripheral
      blood, with the peak being observed at day 6 of treatment. As a result, CD4/CD8
      ratio in blood and spleen was significantly higher in treated than in untreated
      mice. Splenocytes from treated mice proliferated more vigorously in response to
      Con A. When added in vitro, Milife also mildly costimulated Con A-induced
      proliferation of splenocytes from intact animals. In conclusion, we have found
      that Milife can stimulate leuko- and lymphopoesis in BLRB mice, in particular,
      accumulation of CD4+ T cells in peripheral lymphoid organs. We conclude that
      Milife may represent an immunomodulator with the potential to correct T cell
      dysfunction in patients with immunodeficiency.

PMID- 9543704
TI  - Solanum lyratum inhibits anaphylactic reaction and suppresses the expression of L
      histidine decarboxylase mRNA.
AB  - We investigated the effect of aqueous extract of Soloanum lyratum THUNB.
      (Solanaceae) (SLAE) on anaphylactic reaction. The mast cell is widely thought to
      contribute to the acute changes associated with anaphylaxis. SLAE inhibited skin
      mast cells-mediated anaphylactic reaction activated by anti-dinitrophenyl (DNP)
      IgE. SLAE dose-dependently inhibited histamine release in mouse peritoneal mast
      cells activated by anti-DNP IgE or substance P. Substance P increased steady
      state levels of L-histidine decarboxylase (HDC) mRNA in mouse mastocytoma P-815
      cells. Northern-blot analysis demonstrated that significantly reduced level of
      the mRNA of HDC was expressed in mast cells treated with SLAE, compared to that
      without SLAE. We conclude that SLAE directly affect IgE-mediated anaphylactic
      reaction and substance P-induced HDC mRNA over-expression.

PMID- 9543705
TI  - Evaluation of nitric oxide production by Leishmania infantum-infected dog
      macrophages.
AB  - Protozoa of the genus Leishmania (L.) infect reticuloendothelial cells of several
      mammalian species, including dogs, in which they often give rise to a chronic,
      not self-healing visceral disease. Since the parasitocidal mechanism of
      macrophages towards Leishmania in dog has not yet been well investigated, in this
      work we have evaluated in Leishmania infantum-infected macrophage cultures from
      10 healthy dogs, killing capacity and nitric oxide (NO) production, in terms of
      nitrite (NO2) levels. Parallel experiments were performed on macrophages
      stimulated with both Concanavalin A (ConA)-activated PBMC supernatants and
      Salmonella typhimurium lipopolysaccharide (LPS), and in the same conditions, but
      in the presence of the NO synthase inhibitor L-N monomethylarginine (L-NMMA). In
      L. infantum-infected macrophages, nitric oxide production was observed at a
      concentration significantly higher after stimulation with both Con A-activated
      PBMC supernatants and LPS than that observed in uninfected cells cultured in
      medium alone, or infected cells unstimulated or stimulated by PBMC supernatants
      or LPS alone, respectively. Moreover, NO production was abolished in the presence
      of the NO synthase inhibitor L-NMMA. Finally, killing of Leishmania by
      macrophages was significantly reduced in the presence of L-NMMA.

PMID- 9543706
TI  - Effect of streptolysin-O-on rat hepatic acetyl coenzyme-A: arylamine N
      acetyltransferase and cytochrome P-450 2B 1/2 activities ex vivo.
AB  - Numerous immunostimulants have been found to increase N-acetylation in vivo but
      are not associated with a similar increase in vitro. Streptolysin-O (SLO), a
      thiol-activated (oxygen-labile) hemolytic and immune-stimulating exotoxin
      produced by group A streptococci, has been reported to increase the metabolic
      rate constant for sulfamethazine in vivo and arylamine N-acetyltransferase (NAT)
      activity toward procainamide (PA) ex vivo. The effect of SLO pretreatment of rats
      on cytochrome P-450-catalyzed tolbutamide hydroxylation and NAT activities toward
      PA (a substrate for NAT1), and p-aminobenzoic acid (a substrate for NAT2) was
      examined ex vivo. Subacute SLO (SIGMA Chemical Company, St. Louis, MO)
      pretreatment (100 Hemolytic Units/kg/day, intraperitoneal, for 4 days) did not
      alter body weight, liver weight or cytosolic protein content as compared with
      controls. SLO-pretreatment did not alter NAT activities measured ex vivo, nor was
      an alteration in tolbutamide hydroxylation observed. Pretreatment with an
      alternative SLO preparation (DIFCO Laboratories, Detroit, MI) also failed to
      alter the parameters of body weight, liver weight or cytosolic protein content as
      compared with controls. While treated animals had significantly reduced
      microsomal protein content, SLO pretreatment failed to alter the enzyme
      activities measured. We conclude that SLO does not serve as a useful model
      immunostimulant for mechanistic studies as it produces no consistent effect on
      drug metabolizing enzymes.

PMID- 9543707
TI  - Dietary quercetin, immune functions and colonic carcinogenesis in rats.
AB  - Rats fed 100 mg/kg quercetin (QUE) daily for 7 weeks had significantly enhanced
      natural killer cell activity compared to their vehicle (VEH)-fed control. In
      contrast, rats fed 100 mg/kg QUE and treated with the colon carcinogen,
      azoxymethane had significantly reduced natural killer cell activity compared to
      their VEH-fed azoxymethane-treated control. There was no significant difference
      in natural killer cell activity between the two control groups. Antibody
      production and delayed-type hypersensitivity were not altered by QUE feeding in
      any treatment group. In vitro exposure of splenic natural killer cells to 1mM QUE
      significantly decreased natural killer cell cytotoxicity. Lower QUE
      concentrations produced a non-significant reduction in natural killer cell
      activity that was restored to control values at 1 x 10(-13)M QUE. The
      distribution, multiplicity and total number of colonic preneoplastic lesions,
      aberrant crypt foci, was not significantly different in the QUE-fed azoxymethane
      treated rats when compared to azoxymethane-treated vehicle-fed rats at the
      conclusion of 7 week feeding period. We found no correlation between immune
      function and development of preneoplastic colon lesions in this study.

PMID- 9543708
TI  - Therapeutic efficacy of Ashwagandha against experimental aspergillosis in mice.
AB  - Therapeutic efficacy of an Indian Ayurvedic medicinal preparation, Ashwagandha
      [Withania somnifera L. Dunal (Solanceae; root)] was evaluated against
      experimental aspergillosis in Balb/c mice. Ashwagandha given orally once daily
      for 7 consecutive days in a dose of 100 mg/kg after intravenous infection of
      Aspergillus fumigatus prolonged the survival period of infected mice. This
      protective activity was probably related to the observed increases in
      phagocytosis and intracellular killing of peritoneal macrophages induced by
      Ashwaganda treatment. The number of peripheral leukocytes was not modified,
      excluding a possibility of mobilization of cells from other compartments. On the
      basis of these findings, the probable mechanism underlying the protective action
      of Ashwagandha against systemic Aspergillus infection was discussed in relation
      with its possible activity to activate the macrophage function.

PMID- 9543709
TI  - Purification and characterization of a male-specific protein in the hemolymph of
      the wax moth, Galleria mellonella L.
AB  - A male-specific protein (MSP) present only in males was identified from the
      hemolymph of the wax moth, Galleria mellonella L., by polyacrylamide gel
      electrophoresis (PAGE) and purified by anion-exchange chromatography. MSP has a
      native molecular mass of 55 kDa and consists of two 27-kDa subunits. An
      isoelectric point of MSP was measured to be approximately 5.8. MSP is a
      glycoprotein that contains 1.7% carbohydrate. The compositional analysis of
      carbohydrate component indicated a predominance of fructose and glucose. MSP also
      contains large amounts of asparagine, aspartic acid, glutamine, glutamic acid,
      and lysine but small amounts of tyrosine, methionine, and tryptophan. Western
      blot analysis of the hemolymph of each developmental stage indicated that MSP is
      present in the hemolymph of 8-day-old pupa and adult. Also, results from Western
      blotting indicated that MSP is not present in the tissues of larvae and of female
      adults but appears in the fat body of male pupae and adult and testis of adult.
      The fat body and testis of male pupae and adult were cultured in vitro to trace
      the place and time of MSP synthesis. The fat body began to synthesize MSP in late
      pupae and showed active synthesis during the adult stage. The distribution of MSP
      in the testis was observed by electron microscopic immunogold labeling, using the
      antibody against MSP. MSP is present between the germinal cysts and is taken up
      through the basal surface of the seminiferous tubular epithelium.

PMID- 9543710
TI  - Localization of allatostatin-immunoreactive material in the central nervous
      system, stomatogastric nervous system, and gut of the cockroach Blattella
      germanica.
AB  - Immunoreactivity against peptides of the allatostatin family having a typical
      YXFGL-NH2 C-terminus has been localized in different areas of the central nervous
      system, stomatogastric nervous system and gut of the cockroach Blattella
      germanica. In the protocerebrum, the most characteristic immunoreactive perikarya
      are situated in the lateral and median neurosecretory cell groups. Immunoreactive
      median neurosecretory cells send their axons around the circumesophageal
      connectives to form arborizations in the anterior neuropil of the tritocerebrum.
      A group of cells in the lateral aspect of the tritocerebrum project to the
      antennal lobes in the deutocerebrum, where immunoreactive arborizations can be
      seen in the periphery of individual glomeruli. Nerve terminals were shown in the
      corpora allata. These terminals come from perikarya situated in the lateral
      neurosecretory cells in the pars lateralis and in the subesophageal ganglion.
      Immunoreactive axons from median neurosecretory cells and from cells positioned
      in the anteriormost part of the tritocerebrum enter together in the
      stomatogastric nervous system and innervate foregut and midgut, especially the
      crop and the valve between the crop and the midgut. The hindgut is innervated by
      neurons whose perikarya are located in the last abdominal ganglion. Besides
      immunoreactivity in neurons, allatostatin-immunoreactive material is present in
      endocrine cells distributed within the whole midgut epithelium. Possible
      functions for these peptides according to their localization are discussed.

PMID- 9543712
TI  - Binding of heterocyclic amines by lactic acid bacteria from miso, a fermented
      Japanese food.
AB  - Miso, a widely used Japanese fermented food was analysed for its lactic acid
      bacterial count on bromocresol purple agar. The binding of eight different
      foodborne carcinogenic heterocyclic amines to 25 bacterial isolates from miso
      were investigated. The heterocyclic amines used were 3-amino-1,4
      dimethyl[5H]pyrido(4,3-b)indole (Trp-P-1), 3-amino-1-methyl[5H]pyrido(4,3
      b)indole (Trp-P-2), 2-amino-6-methyldipyrido(1,2-a:3'2'-d)imidazole (Glu-P-1), 2
      amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino
      dimethylimidazo(4,5f)quinoline (IQ), 2-amino-3,4-dimethylimidazo(4,5-f) quinoline
      (MeIQ), 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), and 2-amino-3
      methyl-9H-pyrido(2,3)indole (MeA alpha C). The lyophilized cells of all of the
      isolates exhibited high binding activity towards Trp-P-1, Trp-P-2, MeA alpha C,
      and PhIP, while Glu-P-1 and IQ were not effectively bound. Of the isolates
      tested, the strongest and weakest binders were identified as Pediococcus
      acidilactici 1 and 2, respectively. Lyophilized cell wall fractions, heat-treated
      cells, and the cytoplasmic contents of P. acidilactici 1 and 2 were analysed for
      their ability to bind to different mutagens. Pure cell wall and peptidoglycan
      showed greater binding activity than the bacterial cells. Cytoplasmic content
      also showed some binding, but it was much less effective. The impact of enzymes
      (amylase, protease, cellulase, chitinase, muraminase, and peptidase) and
      acetylation of Trp-P-1 and IQ on the binding action of bacteria and cell wall
      material were also analysed to understand the possible processes involved in the
      binding of lactic acid bacteria to carcinogenic heterocyclic amines.

PMID- 9543716
TI  - Molecular characterization of Gluconobacter oxydans recA gene and its inhibitory
      effect on the function of the host wild-type recA gene.
AB  - A DNA fragment containing the recA gene of Gluconobacter oxydans was isolated and
      further characterized for its nucleotide sequence and ability to functionally
      complement various recA mutations. When expressed in an Escherichia coli recA
      host, the G. oxydans recA protein could efficiently function in homologous
      recombination and DNA damage repair. The recA gene's nucleotide sequence analysis
      revealed a protein of 344 amino acids with a molecular mass of 38 kDa. We
      observed an E. coli-like LexA repressor-binding site in the G. oxydans recA gene
      promoter region, suggesting that a LexA-like mediated response system may exist
      in G. oxydans. The expression of G. oxydans recA in E. coli RR1, a recA+ strain,
      surprisingly caused a remarkable reduction of the host wild-type recA gene
      function, whereas the expression of both Serratia marcescens recA and Pseudomonas
      aeruginosa recA gene caused only a slight inhibitory effect on function of the
      host wild-type recA gene product. Compared with the E. coli RecA protein, the
      identity of the amino acid sequence of G. oxydans RecA protein is much lower than
      those RecA proteins of both S. marcescens and Pseudomonas aeruginosa. This result
      suggests that the expression of another wild-type RecA could interfere with host
      wild-type recA gene's function, and the extent of such an interference is
      possibly correlated to the identity of the amino acid sequence between the two
      classes of RecA protein.

PMID- 9543717
TI  - Protease activity of Clostridium difficile strains.
AB  - The production of proteolytic enzymes by 10 Clostridium difficile isolates of
      varying toxigenicity and clinical origin was studied to determine if all isolates
      secreted proteases. Different protease substrates were studied: gelatin,
      collagen, phenylazobenzyloxycarbonyl-leucyl-glycyl-L-prolyl-D-arginine (Pz
      peptide), casein, azocasein, and azocoll. All isolates degraded gelatin,
      collagen, and azocoll. The supernatants of all isolates contained an enzyme
      capable of attacking gelatin incorporated in a polyacrylamide gel (zymograms) and
      forming two closely spaced lytic bands with an estimated molecular mass of 35-40
      kDa. Polyclonal antibodies, produced against the C. difficile gelatinase,
      revealed in Western blots a 35-kDa protein in the culture supernatants of all C.
      difficile isolates. In the same manner, Clostridium perfringens collagenase
      polyclonal antibodies detected a 120-kDa protein in the culture supernatants of
      all isolates; this suggests that at least two proteases may exist in C.
      difficile. The protease activities of the 10 strains examined did not seem
      strikingly different quantitatively but were in general weak and their role in
      pathogenicity is suspect.

PMID- 9543711
TI  - Juvenile hormone acid: evidence for a hormonal function in induction of
      vitellogenin in larvae of Manduca sexta.
AB  - In the tobacco hornworm (Manduca sexta), vitellogenin (Vg), the major yolk
      protein precursor, and its mRNA are first detectable in the prepupal stage; and
      production of both can be enhanced by methoprene, a juvenile hormone (JH) analog.
      Competence to respond to methoprene is acquired after ecdysteroid-initiated
      commitment for metamorphosis. Here we show that acquisition of competence
      requires prior exposure to JH-II acid in addition to ecdysteroid. Application of
      20-hydroxyecdysone or RH5992, an ecdysteroid analog, to isolated abdomens from
      feeding larvae (precommitment) results in exposure of the dorsal vessel (EDV), a
      sign of metamorphic commitment--but such abdomens do not make Vg in response to
      methoprene. However, injection of JH-II acid along with 20-hydroxyecdysone into
      isolated abdomens causes Vg production in response to methoprene. Methoprene acid
      similarly induces competence to respond to methoprene. Northern blot analysis
      confirmed that Vg transcripts are present in fat body only if isolated abdomens
      were pretreated with both ecdysteroid, and JH-II acid or methoprene acid. The
      latter two can induce competence even in precocious prepupae resulting from
      removal of the corpora allata (the glands that produce JH) from early penultimate
      larvae. JH-III acid and related metabolites such as farnesol, farnesoic acid, and
      methyl farnesoate do not induce competence. Hitherto, JH acids have been regarded
      as precursors or catabolites of JHs. Here we show for the first time that JH acid
      has a hormonal function that cannot be performed by JH itself.

PMID- 9543719
TI  - Comparative genome analysis of Bacillus sphaericus by ribotyping, M13
      hybridization, and M13 polymerase chain reaction fingerprinting.
AB  - A comparative genome analysis of 15 strains representing the five homology groups
      of the highly heterogeneous species Bacillus sphaericus was performed by M13
      hybridization fingerprinting, M13 polymerase chain reaction fingerprinting, and
      ribotyping with the whole rrn operon. The computer cluster analyses of the
      polymorphic patterns, presented in dendrograms, showed that these methods allow
      the differentiation of the individual strains and some homology groups. Our
      results confirm the close genetic relatedness of the mosquito pathogenic strains
      of group IIA and support the idea for differentiation of a separate species. At
      the same time, we present additional proof of the significant genetic
      heterogeneity of B. sphaericus and the necessity of reconsideration of its
      present classification.

PMID- 9543720
TI  - Multidrug- and metal-resistant strains of Klebsiella pneumoniae isolated from
      Penaeus monodon of the coastal waters of deltaic Sundarban.
AB  - Marine shrimp of the species Penaeus monodon were collected from the coastal
      region (Haroa) of the deltaic Sundarbans of West Bengal, India during the
      premonsoon period in 1996. Klebsiella pneumoniae was isolated from the alimentary
      canal and gills of the shrimp as the sole isolate. All 10 isolated strains were
      resistant to erythromycin (30 micrograms/mL), ampicillin (100 micrograms/mL),
      furazolidone (100 micrograms/mL), and penicillin (100 IU). These strains were
      able to grow in the presence of silver (Ag+), cobalt (Co2+), cadmium (Cd2+),
      nickel (Ni2+), lead (Pb2+), copper (Cu2+), and zinc (Zn2+) at concentrations up
      to 10 mM. All the strains showed similar plasmid profiles, ranging in sizes from
      1.8 to 120 kb. Resistance to lead, cobalt, nickel, and copper was encoded by a
      3.5-kb plasmid of K. pneumoniae. Synthesis of a 14-kDa periplasmic protein was
      increased when they were grown in presence of 10 mM Cu2+.

PMID- 9543721
TI  - Potentiation of the virucidal activity of sterilized natural waters.
AB  - After heat, conductivity has been described as the second most inactivating
      factor of viruses in surface waters. Using poliovirus-1, we showed that a highly
      significant linear relationship between virus inactivation rate and water
      conductivity can be obtained for most of the tested sterilized water samples.
      Using sterile saline solutions, we demonstrated that this apparent relationship
      is false, i.e., virus inactivation rate is not affected by water conductivity
      alone. With the hypothesis that salts may serve to potentiate the antiviral
      activities of certain microbiological substances that are supposed to be found in
      the tested samples, we can explain the apparent relationship observed in this
      study and in similar ones. As a consequence, an effective water treatment could
      be responsible for the removal of both viruses and some virus-inactivating
      factors. Alternatively, virus-inactivating capability of a given water resource
      could be enhanced along with its hardness or its degree of mineralization.

PMID- 9543722
TI  - Pentatomic cyclic antagonists and muscarinic receptors: a 30-year review.
AB  - This work is a sequel to and completes the review, that recently appeared in this
      journal, of pentatomic cyclic muscarinic agonists. It reports the results of
      structure-activity relationship (SAR) studies of pentatomic cyclic antagonists on
      muscarinic receptors and compares these results with some recent advances in
      molecular biology and quantitative structure-activity relationship (QSAR)
      studies.

PMID- 9543723
TI  - Synthesis and anti-ulcer activity of new derivatives of glycyrrhetic, oleanolic
      and ursolic acids.
AB  - A review is made of the literature describing the structural changes to
      glycyrrhetic, oleanolic and ursolic acids and their influence on anti-ulcer
      activity. For the glycyrrhetic acid derivatives some analogues were prepared in
      which the ketonic group in position 11 was removed and the carboxylic function at
      position 30 was either intact, reduced to alcohol or transformed into ketone.
      This first series of compounds suggests the possibility of obtaining compounds
      devoid of the conjugated ketonic group, maintaining anti-ulcer activity but with
      reduced or lacking mineralocorticoid activity. Based on these findings, a series
      of carbenoxolone analogues in the beta-amyrin series of glycyrrhetic and
      oleanolic acid was prepared. In particular, the delta 9,11 unsaturated compounds
      14b and 23b and the 11-methylene derivative 18 present advantages in terms of
      acute toxicity and mineralocorticoid activity as compared to the reference
      compound. The derivative 14b in the volunteer showed an increase of gastric PGE2
      levels with minor pseudoaldosteronic effect. Among the ursolic acid derivatives,
      the dihemisuccinate sodium salt 35b demonstrated a good separation between anti
      ulcer and mineralocorticoid activities. Nevertheless, kidney and liver toxicity
      was observed in the monkey thus jeopardizing its further development. Better
      results were obtained with the uvaol dihemiphthalate sodium salt and the diene
      analogue 39b. In particular, 38b and 39b showed a potent anti-ulcer activity, 3-
      to 25-fold higher than carbenoxolone. Furthermore, compound 38b does not show
      signs of liver toxicity in the monkey.

PMID- 9543724
TI  - Glycosidopyrroles. Part 1. Acyclic derivatives: 1-(2-hydroxyethoxy)methylpyrroles
      as potential anti-viral agents.
AB  - Acyclic glycosidopyrroles of type 1, synthesized in good overall yields, were
      evaluated for anti-viral activity. Compound 10i was found to inhibit the HIV-1
      replication at concentrations that were very close to those cytotoxic for MT-4
      cells. Compounds 10a,f,i inhibited both strains HSV-1 and HSV-2 at concentrations
      slightly below those cytotoxic for Vero cells. However for this series of
      glycosidopyrroles some relationship between calculated log P values and the
      observed cytotoxicity was found.

PMID- 9543725
TI  - Stereoisomeric effect on antimicrobial activity of a series of quaternary
      ammonium salts.
AB  - Two homologous series of diastereoisomeric racemic +/- cis and +/- trans-N,N
      dimethyl-N-alkyl-2-benzoyloxycyclohexylmethylammonium bromides with the number of
      carbon atoms in the alkyl chain from six to twenty (m = 6,8 ... 20) were
      synthesised. Their structures have been elucidated by IR, UV and in some cases
      also with 1H and 13C NMR spectrometry. The title compounds were assayed for their
      antimicrobial activity on microorganisms S. aureus, E. coli and C. albicans. The
      highest antimicrobial activity was observed against S. aureus (log 1/MIC = 5.5
      mol-1 dm3) and the lowest against E. coli (log 1/MIC = 4.5 mol-1 dm3). The +/-
      cis and +/- trans stereoisomers of all eight couples of diastereoisomeric
      compounds show differences in their physico-chemical characteristics (including
      partition coefficient and lipophilicity) which is also reflected in the different
      antimicrobial activity of these diastereoisomers.

PMID- 9543726
TI  - Diastereomeric separation of 1,5-benzodiazepines due to the presence of a chiral
      centre on the N-5 alkylic chain.
AB  - The presence of a chain bearing a stereogenic centre at the N-5 position of 1-(1
      adamantylmethyl)-3-arylureido-2,4-dioxo-1,5-benzodiazep ines induces optical
      resolution. The synthesis of these compounds and their potency as potential CCK-B
      receptor antagonists is discussed briefly here.

PMID- 9543727
TI  - Further studies on analgesic activity of cyclic imides.
AB  - As part of our research programme to obtain pharmacologically active compounds
      structurally related to cyclic imides, we have synthesized different compounds
      and examined their analgesic activities using the abdominal constriction test in
      mice. The results showed that some of the compounds studied, given
      intraperitoneally, exhibited graded and significant analgesia against acetic acid
      induced abdominal constriction, being several times more potent than aspirin and
      paracetamol, two standard drugs used for comparison.

PMID- 9543728
TI  - Synthesis and in vitro and in vivo evaluation of dopaminergic ergoline
      derivatives.
AB  - A series of ergoline-amides was synthesised in the discovery of new
      dopaminomimetic agents. Several compounds exhibited in vivo high prolactin
      lowering activity (indirectly measured by the nidation test) in rats. For the
      most active, the potential anti-Parkinson activity was evaluated by observation
      of the contralateral turning behaviour in 6-OH-DA lesioned rats. The acute
      toxicity by oral route in mice was also studied.

PMID- 9543729
TI  - Anti-nociceptive and anti-inflammatory activity of some (2-benzoxazolone-3-yl and
      2-benzothiazolone-3-yl)acetic acid derivatives.
AB  - Sixteen (2-benzothiazolone-3-yl and 2-benzoxazolone-3-yl) acetic acid derivatives
      5 have been tested for anti-nociceptive and anti-inflammatory activity in this
      study, 4-[2-(6-Benzoyl-2-benzoxazolone-3-yl)acetyl]morpholine (5c), 4-?2-[6-(2
      chloro-benzoyl)-2-benzoxazolone-3-yl]acetyl?morpholine (5d), 1-[2-(5-chloro-2
      benzoxazolone-3-yl)acetyl]pyrrolidine (5f), methyl (6-methyl-2-benzoxazolone-3
      yl)acetate (5k) and N,N-diethyl-2-(2-benzothiazolone-3-yl)acetamide (5m) have
      shown more potent anti-nociceptive activity than others. Among these compounds,
      5c, 5d and 5m have exhibited good anti-inflammatory activity, with 5f, and to a
      lesser extent, the other molecules displaying some toxic potential.

PMID- 9543730
TI  - Antioxidant activity of some ascorbic and cinnamic acids derivatives.
AB  - Some 4-benzoyl 3-hydroxy furan-2 (5H) ones (3a-d) and 2-amino 3-hydroxymethyl 4
      aryl 4-oxo 2-butenoic acids (4a-h) have been synthesized. Compound 3c with an
      isobutyl substituent in the 5-position of the furan ring was the most effective
      (IC50 = 8.69 x 10(-4) M) in scavenging the superoxide anion. In vivo, 3c was also
      protective against reperfusion injury.

PMID- 9543731
TI  - Fatal attack among wedge-capped capuchins.

PMID- 9543732
TI  - Indiscriminate response to infant calls in wild patas monkeys (Erythrocebus
      patas).

PMID- 9543733
TI  - Adoption and social interactions between a mother and 'twin' offspring in Macaca
      fuscata.

PMID- 9543734
TI  - [Chronic fatigue--'tired with 23 i's'].
AB  - Two patients, a woman aged 32 years and a man aged 49, presented with severe
      chronic fatigue. The woman had chronic fatigue syndrome; she recovered slowly.
      The man suffered from a pituitary adenoma producing follicle stimulating hormone;
      he recovered after transsphenoidal hypophysectomy. In patients with chronic
      fatigue, the history and a thorough physical examination to exclude underlying
      illness are very important; secondary symptom criteria must not be overemphasized
      (as is the case with the Holmes and Fukuda criteria), chronic fatigue syndrome
      should not be diagnosed if the condition has a shorter duration than 6 months,
      but it should be diagnosed if the clinical picture is compatible. The prognosis
      is not poor: in patients with a median disease duration of 4.5 years, 20% show
      significant improvement over an 18-month period.

PMID- 9543735
TI  - [Chronic fatigue syndrome].
AB  - Chronic fatigue syndrome is a controversial disease entity. Opinions range from
      non-disease via psychiatric disorder to a somatic disturbance. Somatic
      pathogenetic hypotheses include persisting infections, intoxications, metabolic
      or immunologic disturbances, nervous system diseases and endocrine pathology.
      None of these hypotheses has been substantiated as yet. Psychological factors are
      important in the course of the disorder and can be used in the therapeutic
      approach of patients with chronic fatigue syndrome.

PMID- 9543736
TI  - [Attributions and chronic fatigue].
AB  - It was recently suggested that chronic fatigue is merely a question of
      attribution. Attribution clearly contributes to the course of chronic fatigue
      syndrome (CFS) but is not its sole determinant. The presence of strong somatic
      attributions appears to be one of the perpetuating factors in CFS but not the
      only one. Many CFS patients present a self-diagnosis, e.g. myalgic
      encephalomyelitis. Communication problems between patient and doctor easily arise
      because of different attributions of the complaints. At the start of fatigue
      somatic attributions are of less importance than later on in the course of the
      complaints. In this process an iatrogenic factor might be involved. On the other
      hand doctors are able to influence these attributions actively in a favourable
      direction.

PMID- 9543737
TI  - [Chronic fatigue syndrome in young persons].
AB  - The prevalence of chronic fatigue syndrome (CFS) in teenagers is 10-20 per
      100,000 inhabitants in the Netherlands. The natural course of the disorder is not
      favourable according to the literature. Proposed criteria for the diagnosis 'CFS'
      in adolescence are: absence of a physical explanation for the complaints, a
      disabling fatigue for at least six months and prolonged school absenteeism or
      severe motor and social disabilities. Exclusion criterion should be a psychiatric
      disorder. Factors that attribute to the persistence of fatigue are somatic
      attributions, illness enhancing cognitions and behaviour of parents as well as
      physical inactivity. The role of the physician and the role of parents can
      enhance the problems. The treatment should focus on decreasing the somatic
      attributions, on reinforcement by the parents of healthy adolescent behaviour, on
      the gradual increase of physical activity and on decreasing attention (including
      medical attention) for the somatic complaints.

PMID- 9543738
TI  - [Indications for management in long-term, physically unexplained fatigue
      symptoms].
AB  - In meetings arranged by the minister of Public Health, Welfare and Sports between
      general practitioners and specialists concerning chronic fatigue syndrome (CFS),
      suggestions for the diagnosis, treatment and assistance and support of patients
      with protracted physically unexplained fatigue symptoms, were established in the
      light of current scientific insight. The term 'CFS' is applicable in cases of
      fatigue complaints, of at least 6 months' standing, reported by the patient
      himself and evaluated medically, for which no physical explanation has been found
      and which cause considerable disabilities in professional social and/or personal
      functioning. The management depends on the duration of the illness. A distinction
      is made between an acute phase (up to one month after the first consultation; the
      policy is mostly expectative), a subacute phase (until 6 months after the onset
      of the complaints and disabilities; the management is aimed at making the patient
      accept the condition and persuading him or her to make an effort to promote
      health) and a chronic phase (from 6 months after the onset of the complaints and
      disabilities; the management is aimed at health-promoting behaviour and
      cognitions). Further (laboratory) examinations are useful only if the symptoms
      have not disappeared after one month (this is the case in approximately 20% of
      the patients); such examinations may be useful in older patients earlier. It is
      important that the CFS patient learns to realize that it is useless to continue
      to spend energy on searching for causes and possible therapies, but that he
      should try to promote his own health, for instance by means of a quantified
      programme of activities linked to a time schedule (instead of to a level of
      fatigue).

PMID- 9543739
TI  - [Prevalence of chronic fatigue syndrome and primary fibromyalgia syndrome in The
      Netherlands].
AB  - OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) and of
      primary fibromyalgia syndrome (PFS) in the Netherlands. DESIGN: Questionnaire.
      SETTING: Department of Medical Psychology, University Hospital Nijmegen, the
      Netherlands. METHOD: A questionnaire was mailed to all the 6657 general
      practitioners in the Netherlands in order to inform them of the existence of CFS
      and to ask them if they had any CFS or PFS patients in their practices. RESULTS:
      Sixty percent (n = 4027) of the general practitioners returned the questionnaire.
      Of all the general practitioners, 27% said they had no CFS patients, 23% said
      they had 1 CFS patient, while 21% had 2 CFS patients, and 29% said they had 3 or
      more CFS patients in their practice. Concerning PFS the results were 17% (no PFS
      patients), 18%, 18% and 47%, respectively. With a mean practice of 2486 patients
      per general practice, the estimated prevalence of CFS was 112 per 100,000 and
      that of PFS 157 per 100,000 persons. Of the CFS patients 81% were women and 55%
      were 25-44 years old; for PFS these figures were 87% and 48% respectively.
      CONCLUSION: Extrapolation of the study results indicates that there are at least
      17,000 CFS patients and 24,000 PFS patients in the Netherlands. The found
      prevalence is probably an under-estimation.

PMID- 9543740
TI  - [Prevalence of chronic fatigue syndrome in 4 family practices in Leiden].
AB  - OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) in
      general practice. DESIGN: Descriptive. SETTING: General practice and primary
      health care centres in Leyden region, the Netherlands. METHOD: RNUH-LEO is a
      computerized database which contains the anonymous patient information of one
      general practice (with two practitioners) and four primary health care centres.
      The fourteen participating general practitioners were asked what International
      Classification of Primary Care (ICPC) code they used to indicate a patient with
      chronic fatigue or with CFS. With these codes and with the code for depression
      patients were selected from the database. It then was determined whether these
      patients met the criteria of CFS by Holmes et al. RESULTS: The general
      practitioners used 10 codes. Including the code for depression a total of 601
      patients were preselected from a total of 23,000 patients in the database. Based
      on the information from the patients' records in the database, 42 of the
      preselected patients were selected who might fulfill the Holmes' criteria of CFS.
      According to the patients' own general practitioner, 25 of the 42 patients would
      fulfil the Holmes' criteria. The men:women ratio was 1:5. The prevalence of CFS
      in the population surveyed was estimated to be at least 1.1 per 1,000 patients.

PMID- 9543741
TI  - ['Abbreviated fatigue questionnaire': a practical tool in the classification of
      fatigue].
AB  - The 'Shortened fatigue questionnaire' (SFQ) is a short, reliable and easily used
      instrument to determine the intensity of the patient's bodily fatigue. It
      consists of four questions which the patient answers by checking an item at a 7
      point scale ('I feel tired', 'I tire easily', 'I feel fit' and 'I feel physically
      exhausted'). The physician can then calculate a total score and compare it with
      the score in standard groups (standardized by load-bearing). The questionnaire
      can be completed simply and quickly. It constitutes a valuable addition in daily
      medical practice and in clinical scientific studies for the assessment of fatigue
      complaints.

PMID- 9543743
TI  - [Synopsis of the revised standard 'stomach symptoms' of the Nederlands Huisartsen
      Genootschap].

PMID- 9543744
TI  - [Temperature measurement in adults: equally good results using the tympanic
      membrane thermometer and the rectal digital thermometer in the Internal Medicine
      department].

PMID- 9543745
TI  - [Acetylcysteine in children with lung disorders prescribed by one third of family
      physicians; no support in the literature].

PMID- 9543746
TI  - [Peritoneal pseudomyxoma].

PMID- 9543747
TI  - [Medical and administrative disregard of a high blood sugar value; notes on a
      decision by the medical disciplinary tribunal].

PMID- 9543748
TI  - [Allogeneic bone marrow transplantation of unrelated donors; fewer complication,
      more donors].
AB  - A female patient aged 37 years who suffered from chronic myeloid leukemia
      received an allogeneic bone marrow transplantation (BMT) from an HLA-matched
      unrelated donor. No life-threatening complications ensued; 2.5 years after BMT
      she is still in complete remission. Survival after BMT from an unrelated donor
      for the time being is still lower than that after BMT from a related donor, but
      is improving due to better prevention and treatment of opportunistic infections
      and better selection of registered donors by meticulous HLA matching.

PMID- 9543749
TI  - [Hospital Infection Epidemiology Nederland (ZIEN): from club to study group].
AB  - Medical care is increasingly a technical business, and hospitalised patients are
      more and more susceptible to infections, notably due to the application of
      aggressive therapies for all kinds of disorders. As a consequence the
      epidemiology of hospital infections requires serious attention. Following the
      initiative of some medical microbiologists in the Netherlands, a study group was
      established to tackle this epidemiology and to initiate relevant research
      (Working party on Hospital Infections and Epidemiology of the Netherlands; WHEN).
      Recent subjects include fungemia in hospitalised patients, risk factors for
      acquiring methicillin-resistant Staphylococcus aureus during a stay abroad, and
      prevalence of vancomycin-resistant enterococci.

PMID- 9543750
TI  - [Contact allergy for corticosteroids].
AB  - Contact allergy to corticosteroids is not rare. In some studies prevalence rates
      up to 6% have been observed among patients suspected of allergic contact
      dermatitis. Hypersensitivity occurs especially in individuals who have been
      suffering for years from atopic dermatitis, contact dermatitis of the hands and
      feet, or stasis dermatitis caused by chronic venous insufficiency. The clinical
      picture is rarely that of acute allergic contact dermatitis, because the reaction
      is mitigated by the anti-inflammatory properties of the corticosteroid itself;
      the diagnosis must be suspected when eczema does not improve or spreads during
      topical corticosteroid therapy. Application to the mucous membranes less
      frequently leads to sensitisation. Most such cases are caused by nasal sprays
      containing tixocortol pivalate or budesonide. Oral or parenteral administration
      of corticosteroids to sensitive individuals causes exacerbation of pre-existing
      contact dermatitis or widespread allergic cutaneous drug reactions.
      Allergological investigation with corticosteroids presents some specific
      problems, the most important being occurrence of false-negative reactions.
      Nevertheless, most sensitive patients can be identified by testing the
      'indicator' allergens, budesonide and tixocortol pivalate, which should be added
      to the routine series of contact allergens. Cross-reactions to other
      corticosteroids occur frequently. This should be taken into account when
      prescribing alternative corticosteroid preparations.

PMID- 9543751
TI  - [More than 10 years of revision-cleaning and revision-reconstructive ear surgery
      in chronic otitis media; good long-term results].
AB  - OBJECTIVE: To describe the long-term results of revision surgery in patients with
      chronic otitis media. SETTING: University Hospital, Utrecht, the Netherlands.
      METHODS: A personal series of 323 revision mastoidectomies and (or) revision
      tympanoplasties was evaluated. Surgery was performed between 1981-1995 with a
      follow-up of one (minimal) to 14 years (maximal). Anatomical and functional
      results of various subgroups were compared. RESULTS: A preoperative incidence of
      cholesteatoma of 34% (n = 99) dropped after revision surgery to 11%
      residual/recurrent cholesteatomas (n = 9). A dry, safe and disease-free ear with
      a closed tympanic membrane was obtained in nearly 90% of the cases. However, in
      5% (n = 10) without pre-existent cholesteatoma (n = 199), a cholesteatoma
      developed de novo after revision surgery. A residual air-bone hearing gap < or =
      30 dB resulted in 79% of the patients after revision tympanoplasty only (n = 27).
      Revision mastoidectomy with revision tympanoplasty in open (n = 91) and closed (n
      = 92) procedures lead to a residual air-bone gap < or = 30 dB in 56% of the open
      cases (n = 91) and in 73% of the closed cases (before the operation the figures
      were 37% and 55% respectively). CONCLUSION: Revision mastoid surgery and (or)
      revision tympanoplasty can be quite rewarding and successful.

PMID- 9543752
TI  - [Sore throat in rheumatoid arthritis: 2 patients with cricoarytenoid arthritis].
AB  - In two patients with chronic rheumatoid arthritis, a woman aged 65 and a man aged
      56 years, cricoarytenoid arthritis was diagnosed. The symptoms were hoarseness,
      sore throat and stridor. In both patients a narrowed glottic fissure was found.
      In one patient tracheostomy was necessary to guarantee a free airway; in the
      other, therapy with local corticosteroid injections (triamcinolone), combined
      with immunosuppressive therapy (prednisone), was effective. Early detection
      through anamnesis and laryngoscopy allows early therapy with a good prognosis.

PMID- 9543753
TI  - [Infection with T-lymphotropic virus in Dutch blood donors, 1993-1996].
AB  - Infection with human T-lymphotrophic virus (HTLV) type 1 causes a neurological
      disorder or leukaemia in a minority of infected persons. Since January 1993 the
      Dutch blood banks screen each donation for presence of HTLV-1 infection.
      Approximately 4,000,000 donations from 700,000 donors have been tested. The
      numbers of confirmed HTLV-1 positive donors were: 1993: 15; 1994: 6; 1995: 8;
      1996: 3. In 1995 one case of HTLV-2 infection was detected as well. In 26/32
      (81%) of the HTLV-1 positive cases either the donor or his/her partner originated
      from HTLV-1 endemic areas. The introduction of HTLV screening prevents the silent
      spread of HTLV via blood transfusion.

PMID- 9543754
TI  - [Communication between treating physician and occupational physician in the
      management of absenteeism].
AB  - In case of an employee's absenteeism, both the treating physician and the company
      doctor possess relevant medical information. With a view to reducing absenteeism,
      exchange of data is considered important. Provision of data requires the consent
      of the patient/employee. If the latter is informed of the purpose for which the
      data are requested and of how they will be used, medical professional secrecy is
      not violated. In order to enhance the exchange of data between treating physician
      and company doctor, without bypassing the requirement of consent or cancelling
      the division between treatment and checking, the treating physician should be
      permitted to provide more information than just the data asked for in specific
      questions. This however requires the development of guidelines for careful
      consultation.

PMID- 9543755
TI  - [In which childbirth should endocarditis prophylaxis be given?].

PMID- 9543756
TI  - [Peer review in request for subsidy].

PMID- 9543757
TI  - [Pleural mesothelioma in family practice; complicated pain problems].

PMID- 9543758
TI  - [Pleural mesothelioma in family practice; complicated pain problems].

PMID- 9543759
TI  - [Plastic surgery as a last resort in lichen sclerosus].

PMID- 9543760
TI  - [Hypertension in the acute phase of brain infarct; generally do not treat].

PMID- 9543761
TI  - [Low birth weight and risk of heart and vascular diseases].

PMID- 9543762
TI  - [Increasing incidence of mesothelioma in the future due to occupational exposure
      to asbestos in the past].

PMID- 9543763
TI  - [Neurological presentation of non-Hodgkin lymphoma: a diagnostic problem].
AB  - In two patients, men aged 69 and 38 years, neurological signs were the first
      presenting symptoms of systemic non-Hodgkin's lymphoma (NHL). This presentation
      is uncommon. The patients had focal neurological deficit and elevated serum
      lactate dehydrogenase (LDH) activity. Neurological manifestations of NHL may be
      caused by extradural lymphoma or by diffuse leptomeningeal metastasis (meningitis
      lymphomatosa). A third patient, a woman of 48, had a third form of nervous system
      involvement, primary cerebral NHL, which is not a metastatic sequel to systemic
      NHL. Primary neurological presentation of NHL may be difficult to diagnose,
      particularly in case of prior treatment with corticosteroids.

PMID- 9543764
TI  - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia
      applicable in The Netherlands as well].
AB  - There are three Anglo-Saxon guidelines for the management of patients with a
      community-acquired pneumonia: an American, a British and a Canadian one. The
      guidelines correspond fairly well. There is a subdivision into categories
      according to whether the patients are treated at home (formerly healthy patients
      younger than 60 years versus patients with pre-existent disease or aged 60 years
      and more) or in the hospital (patients not needing intensive care versus those
      who do need it). For each category the most common causative micro-organisms are
      listed together with recommended antibiotic treatment. The Canadian guidelines
      have nursing home patients as a separate category because of slightly different
      causative organisms due to frequent microaspiration. The guidelines are
      applicable to the situation in the Netherlands, with a few exceptions: antibiotic
      resistance is not a major problem in the Netherlands (as yet), and contrary to
      what the guidelines state an agent with activity against Pseudomonas aeruginosa
      is not necessary; the same agents as in category III can be prescribed in these
      patients. A macrolide or azalide antibiotic is advisable for intensive care
      patients in view of the possibility of infection with Legionella pneumophila or
      Mycoplasma pneumoniae.

PMID- 9543765
TI  - [Current lymphoma classification: a step forward for pathologists and
      clinicians].
AB  - Non-Hodgkin lymphomas encompass a heterogeneous group of lymphoid malignancies
      from the clinical as well as from the pathological point of view. Consequently,
      one condition of optimal communication among pathologists, clinicians and
      scientific researchers is an adequate classification system. A new classification
      of lymphomas was proposed in September 1994, the Revised European-American
      Lymphoma Classification (REAL classification). The REAL classification is aiming
      at integration of pathological and clinical data, making it possible to
      distinguish clinical-pathological entities each of which has its characteristic
      pathological spectrum, clinical evolution and clinical presentation. The REAL
      classification is based not only on morphological and immunohistochemical but
      also on molecular and cytogenetic data. Such a system may make it possible to
      develop specific therapies for specific pathological entities. The REAL
      classification constitutes an important step forward in haemato-oncology.

PMID- 9543767
TI  - [Acute tumor lysis syndrome due to mono-therapy with a corticosteroid in a
      patient with non-Hodgkin lymphoma].
AB  - A 20-year-old man was hospitalised because he nearly suffocated when lying on his
      back. After bronchoscopy which revealed severe external compression of the
      airways, suddenly respiratory insufficiency developed. Because a malignant
      lymphoma was suspected chemotherapy was started, using monotherapy with
      prednisolone as the risk of acute tumour lysis syndrome (ATLS) is high with
      polychemotherapy of bulky tumours. Nevertheless ATLS developed, for which
      haemodialysis had to be applied. The tumour, a T-cell lymphoblastic non-Hodgkin
      lymphoma with high grade malignancy, was treated successfully with
      cyclophosphamide, doxorubicin, vincristine en prednisone. ATLS is characterized
      by hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia, lactate
      acidosis and acute renal failure. It can occur in the course of aggressive
      cytoreductive therapy in rapidly growing lymphoproliferative malignancies with
      large tumour size, due to massive tumour cel lysis. Corticosteroid monotherapy is
      a very rare cause of ATLS.

PMID- 9543768
TI  - [A special case of 'deafness'; Landau-Kleffner syndrome].
AB  - A boy aged 5 had displayed from the age of 3 a fluctuating deficit in
      understanding spoken language. Audiometric testing proved his hearing to be
      normal. After 18 months, the parents noticed minor attacks of 'absence'. An EEG
      showed a normal background pattern and frequent spikes and spike waves complexes;
      CT-scanning of the brain revealed no abnormalities. On the basis of the acquired
      language disorder, the seizures and the features of the nocturnal EEG, the
      diagnosis the syndrome of Landau-Kleffner was made. After treatment with
      ethosuximide a temporary improvement of the aphasia occurred. A permanent
      improvement however was realized by treatment with prednisone. The boy could
      attend a primary school. The syndrome runs a fluctuating course; the patient may
      recover, but he may also undergo general mental deterioration. Antiepileptic
      agents only may have a brief favorable effect on the aphasia. In case of failure
      corticosteroids or even subpial cortical transsection are indicated.

PMID- 9543769
TI  - [Dexamethasone in a non-registered ointment from the Far East].
AB  - The Oriental cream Piyan Ping 999 has been used in the Netherlands as an
      unlicensed product. Chemical analysis revealed the presence of dexamethasone and
      dexamethasone-21-acetate in pharmacologically relevant concentrations. It was
      prescribed for 2 children; the 3-year-old girl had meanwhile developed bruises
      and small, poorly healing wounds.

PMID- 9543770
TI  - [Comparison of regional formularies for family physicians].

PMID- 9543771
TI  - [Comparison of regional formularies for family physicians. Formulariumcommissie
      Formularium Midden-Nederland].

PMID- 9543772
TI  - [Diabetes mellitus in connection with a hereditary disorder].

PMID- 9543773
TI  - [Pregnancy following oocyte donation].
AB  - Five women, aged 31, 26, 31, 34, and 28 years, became pregnant after oocyte
      donation and in-vitro fertilization. One was a carrier of Leber's optical
      atrophy, three had had an early menopause (in two because of chromosomal
      abnormalities), and one had had bilateral ovarian extirpation because of a
      cystadenoma and endometriosis. Three developed (pre-)eclampsia during pregnancy
      and one had a serious fluxus post partum. One twin died in utero, the other
      children were healthy. In the Netherlands in-vitro fertilization (with or without
      egg-donation) takes place up to the age of about 40. Regarding the high incidence
      of obstetrical complications in women under 40, raising the age limit could lead
      to even more pregnancy problems. Candidates for oocyte donation should be
      informed about these risks, furthermore they should not deliver at home.

PMID- 9543774
TI  - [Mood disorders in daily practice; the North American consensus statement on the
      undertreatment of depression].
AB  - The American National Depressive and Manic-Depressive Association consensus
      statement on the undertreatment of depression may have consequences for the
      treatment of patients in the Netherlands. It is concluded that Dutch clinicians,
      also, can be expected to play a more active role in cases of mood disorders than
      formerly. A comparison of the definitions of depressive disorder in the available
      classification system results in the recommendation to be strict about the
      distinction between severe and moderate depressive disorders on the one hand and
      subthreshold or mild conditions on the other. It is expected that this will limit
      the anticipated shift towards a more general willingness to use pharmacotherapy
      for mood disorders in patients in whom this can be expected to be efficacious.

PMID- 9543775
TI  - [The 'medical work disability criterium'].
AB  - Legal texts regarding incapacity to work use normal language and not medical
      jargon. Physicians tend to ignore that, with serious consequences. For instance,
      'disease' (Dutch 'ziekte') in the law text is not identical to 'diagnosis', but
      refers to 'illness' (in Dutch also 'ziekte') as well. Likewise, the term
      'objective criteria' for determining disease/illness not only refers to the
      results of physical examination and of additional laboratory tests and imaging,
      but should also include anamnestic findings provided these are verifiable,
      reproducible and consistent. The law is not about diseases, but about ill people.

PMID- 9543776
TI  - [Microalbuminuria in essential hypertension: of limited value as an indicator of
      patients with a high risk for complications].
AB  - Microalbuminuria is usually defined as a urinary albumin excretion of 30-300
      mg/24 h (i.e. 20-200 micrograms/min) measured, in view of the short-term
      variation of 15-30%, in at least 2 out of 3 urine samples. An alternative
      definition is: an albumin-creatinine ratio of 2-20 mg/mmol creatinine.
      Microalbuminuria is an indicator of an enhanced risk of chronic kidney failure
      and cardiovascular disease in diabetic patients and of cardiovascular disease in
      the elderly general population. It is not known whether these relationships exist
      in essential hypertension as well. In essential hypertension there is, however, a
      relationship between microalbuminuria and endothelial dysfunction, impaired
      regulation of renal haemodynamics and an increased risk of left ventricular
      hypertrophy and hypertensive retinopathy. By screening for microalbuminuria a
      group of patients can be distinguished who have a relatively high risk for the
      presence of complications of hypertension. It is not certain, however, that more
      intensive treatment of such patients (e.g. with ACE inhibitors) is useful.
      Consequently, for the time being, screening of patients with essential
      hypertension for microalbuminuria is of little practical importance.

PMID- 9543777
TI  - [Folic acid use for women desiring offspring: the family physician's response].
AB  - OBJECTIVE: To establish to what extent general practitioners (GP's) are familiar
      with the folic acid campaign of the Netherlands Bureau for Food and Nutrition
      Education, display a positive attitude regarding use of folic acid tablets by
      women who would like to become pregnant and factually provide information on
      folic acid. DESIGN: Cross-sectional, descriptive. SETTING: Regions: Central
      Brabant, Achterhoek, Randstad and Northern Netherlands. METHOD: In 1996 a printed
      questionnaire was sent to 300 GP's selected at random. It contained questions
      about knowledge, attitude and management regarding the use of folic acid by women
      who would like to become pregnant and with a normal risk to have a child with a
      neural tube defect. RESULTS: The response was high (81%). Most GP's were familiar
      with the national campaign on folic acid (87%), but 18% considered themselves
      insufficiently informed about the education campaign and/or the folic acid
      recommendations. Half the GP's considered use of folic acid tablets by women who
      would like to become pregnant as important, while two-thirds were of the opinion
      that it contributed to medicalization of the pregnancy. Most GP's (82%) thought
      that pregnant women who had not used folic acid tablets might develop feelings of
      guilt. Nevertheless, 64% recommended use of folic acid tablets and 63% were
      willing to write a prescription if the woman asked for it. Seventy-five per cent
      of the GP's reported that they themselves suggested use of folic acid tablets to
      women who they assumed would like to become pregnant, although most stated they
      sometimes forgot (58%). The percentages of GP's who sometimes or always suggested
      folic acid tablets during a contraception advice after delivery or who advised
      women who would like to become pregnant to switch to a diet rich in folic acid,
      were much smaller (29 and 37%, respectively). CONCLUSION: Although a large number
      of the GP's mentioned potential problems, the majority actively cooperated in
      promoting use of folic acid by women who would like to become pregnant.

PMID- 9543778
TI  - [A patient with a cytomegalovirus infection and multiple stomach ulcers].
AB  - In a 64-year-old, previously healthy woman an upper gastrointestinal endoscopy
      was performed because of serious dyspeptic complaints during fourteen days.
      Multiple fundic gastric ulcers were found without Helicobacter pylori and the
      patient did not take non-steroidal anti-inflammatory drugs (NSAIDs). The
      diagnosis was primary cytomegalovirus infection, based on the demonstration of
      infected cells in the biopsy specimens, using specific monoclonal anti
      cytomegalovirus antibodies.

PMID- 9543779
TI  - [Immune thrombocytopenia attributed to norfloxacin].
AB  - A 65-year-old woman developed haemorrhagic diathesis due to a profound
      thrombocytopenia (thrombocyte count: 1 x 10(9)/l) within one week after a 10-day
      course of norfloxacin (2 x 400 mg/day), prescribed for cystitis. On account of
      increased megakaryopoiesis in the bone marrow and absence of other causes of
      thrombocytopenia norfloxacin-induced immune thrombocytopenia was diagnosed. No
      norfloxacin-dependent antibodies against platelets were detected. Treatment with
      prednisone (1.5 mg/kg/day) resulted in the normalization of the platelet count
      within 5 days.

PMID- 9543780
TI  - [The Stimulation Program Health Research. X. Evaluation of the program section
      'Psychogeriatrics'].
AB  - In the programme section 'Psychogeriatrics' of the SGO Health Research Promotion
      Programme a longitudinal study was carried out in Amsterdam from 1989 until 1994,
      concerning the course of mild cognitive decline in elderly people (the AMSTEL
      project). The scientific aims were the development of diagnostical instruments
      for the early diagnosis of dementia, the development of criteria which predict
      the course of mild cognitive impairment and the expansion of knowledge on the
      relationship between somatic and psychiatric pathology and dementia. The
      programme also had aims regarding medical education and patient care. The results
      include the following: in order to diagnose dementia in general practice
      questions regarding orientation and short-term memory are helpful. Risk factors
      for cognitive deterioration in elderly people include hippocampal atrophy on the
      MRI scan, a low level of education and subjective complaints regarding memory.
      Subjective complaints regarding memory are not primarily caused by a depressive
      mood, as is often thought, but are important as correct self-observations of
      cognitive deterioration, and go with an increased risk of developing dementia.
      Besides the AMSTEL project a feasibility study was carried out concerning a
      psychogeriatric case register in Amsterdam.

PMID- 9543781
TI  - [The Diagnostisch Kompas; a recent contribution to diagnosis].

PMID- 9543782
TI  - [Automatization of the medical literature and information provisions].

PMID- 9543783
TI  - [Misunderstood symptoms in patients with infectious endocarditis].
AB  - Infectious endocarditis was diagnosed in four patients, men aged 18, 44, 35 and
      22; the bacteria involved were Streptococcus viridans, Eikenella corrodens,
      Staphylococcus aureus and Streptococcus mutans, respectively. In all patients
      mycotic aneurysms were observed which had led to seemingly unrelated neurological
      or abdominal complaints. In one patient an aneurysm of the A. cerebri media
      resolved in two years, another patient died following fatal bleeding of a
      ruptured aneurysm in the A. hepatica propria. Mycotic aneurysms may be found in
      all parts of the body. This complication is often diagnosed too late because it
      is not considered.

PMID- 9543784
TI  - [Application of the Act Special Admissions in Psychiatric Hospitals; balance
      between respect for autonomy and acting in the patient's best interest].
AB  - Three years after the implementation of the Dutch Act on Compulsory Admission to
      Psychiatric Hospitals an evaluation was made. It shows that the law has
      reinforced the patients' rights to self-determination, but that actual practice
      is not yet fully according to the law. For the latter the reporters blame the
      complexity of the law and the inadequate manner in which the law was introduced.
      An evaluation of the effects of a similar law in the USA puts this issue in a
      different light. It shows that caregivers and judges do not let the patient's
      rights to autonomy prevail if this is not in the patient's best interests. The
      right to self-determination, expected in the sixties and seventies to become a
      revolution in psychiatry appears to be merely 'a near-revolution'. The moral
      importance of caring for a psychiatric patient outweighs the respect for his or
      her right to self-determination.

PMID- 9543785
TI  - [Therapeutic applications and biomedical effects of cannabinoids; pharmacological
      starting points].
AB  - A broad range of therapeutic applications has been suggested for cannabis or its
      pharmacologically active compound (tetrahydrocannabinol; THC) in many
      publications. Psychotropic side effects and the anecdotal character of the
      research have limited the pharmacotherapeutic use of THC until now. Therefore,
      the Netherlands Health Council recently decided negatively on this matter.
      Besides several cannabinoid receptor subtypes present in the central nervous
      system and peripheral tissues endogenous cannabinoids have been detected. These
      endogenous cannabinoids appear to play an important role in signal transduction,
      which may be starting points for therapy regarding: cardiovascular diseases,
      multiple sclerosis and spinal cord disorders. cerebrovascular accident and brain
      trauma, neurodegenerative diseases, epilepsy, pain management, glaucoma,
      oncologic and aids-related disorders such as nausea, vomiting and appetite
      problems.

PMID- 9543786
TI  - [Vaccination against hepatitis B possibly indicated for elderly institutionalized
      mentally handicapped persons with isolated anti-HBc positivity of the
      prevaccination serum].
AB  - OBJECTIVE: To determine whether vaccination against hepatitis B may be omitted in
      persons with isolated positive anti-HBc. DESIGN: Prospective study using control
      groups. SETTING'S: Heeren Loo-Lozenoord, Ermelo, the Netherlands. METHOD: Twenty
      six older residents (group P) with isolated anti-HBc positivity (HBsAg negative
      and anti-HBs < 10 IU/l) were given hepatitis B vaccine (3 doses); 16 matched
      controls (group C1) lacking hepatitis B markers, received a primary vaccination
      (3 doses), 8 controls (group C2) with a immune status based on infection in the
      past received vaccination (3 doses) and 27 controls (group C3) were given a
      booster vaccination (1 dose) after vaccination 7 years earlier. The anti-HBs
      response was measured 0, 1 and 7 months after the first vaccine dose. An
      anamnestic response was defined as a fourfold rise of anti-HBs after one dose of
      vaccine or--in the absence of an anti-HBs titer in the prevaccination serum--a
      response > or = 10 IU/l after one dose of vaccine. A primary response was defined
      as an anti-HBs response > or = 10 IU/l after giving 3 vaccines, while the
      criteria for an anamnestic response were not met. RESULTS: In the isolated anti
      HBc group (P) and in the corresponding control group (C2) 15 and 12.5%,
      respectively, showed an anamnestic response; the majority reacted with a primary
      response or did not respond at all. The subjects given a primary vaccination (C1)
      responded in 62.5% with a primary response while those vaccinated earlier (C3)
      responded in 92.6% with a fourfold rise of anti-HBs. CONCLUSIONS: The anti-HBs
      response to vaccination in older mentally handicapped persons is delayed and
      there is a reduced chance of development of a protective anti-HBs titer. The
      majority of individuals with isolated anti-HBc showed a primary response. In
      these persons vaccination should not be omitted, especially if there is a risk of
      hepatitis B.

PMID- 9543787
TI  - [5 children with hypokalemia, hypomagnesemia and hypocalciuria (Gitelman
      syndrome) in one family].
AB  - Gitelman's syndrome was diagnosed in five siblings. The parents were relatives in
      the third remove. Gitelman's syndrome is a rare autosomal recessive hereditary
      magnesium reabsorption defect in the distal tubule. It is characterized by
      episodes of muscle weakness, usually accompanied by abdominal pain and vomiting.
      Tetany may occur during a febrile illness. Patients are of normal height and
      weight and have normal blood pressures. Sometimes eczematous skin lesions are
      found. Biochemically there is hypokalaemia, hypomagnesaemia and alkalosis.
      Urinary excretion rates of potassium and magnesium are elevated, the excretion of
      calcium is diminished. Treatment consists of oral suppletion of magnesium,
      sometimes also with oral potassium. A potassium-sparing diuretic may be used. The
      prognosis appears to be good.

PMID- 9543788
TI  - [Changes in health care in the Middle East and North African regions].
AB  - A three-day conference, Regional Seminar on Health Sector Development, was held
      in Cairo in June 1997. Top policy makers from countries in the region Middle East
      and North Africa were invited. At this conference, the World Bank presented a
      model aimed at solving the health care problems in this region. Egypt was used to
      illustrate the current problems. In this country, birth rate and infant mortality
      are decreasing while the population is increasing. Owing to infectious diseases
      in children and chronic diseases in the elderly, the demand for health care is
      great. However, physicians, pharmacists and nurses frequently are poorly trained
      and more interested in money than in quality of care. Outpatient clinics and
      hospitals are funded by the government and by major companies. In addition there
      are private practices. No reliable statistical data are available. What
      regulation there is, is mostly aimed at users of the health care facilities (to
      limit the demand for care). The World Bank proposal implied that governments
      should be less concerned with the provision of care and more with the regulation
      of care provisions. Care givers' pay should be made dependent on observation of
      rules still to be defined, for instance with regard to rational treatment
      protocols. The Netherlands was presented as an example with regard to the
      (financial) organization of health care. The two countries have been co-operating
      for years in a number of projects. Hopefully, the expertise of the World Bank and
      good co-operation between all countries involved will lead to improvement of the
      health care in the region Middle East and North Africa.

PMID- 9543789
TI  - [Changes in therapy-resistant primary depression].

PMID- 9543790
TI  - [Hypothermia in patients with a high spinal cord lesion].

PMID- 9543791
TI  - [Side effects of minocycline in the treatment of acne vulgaris. Dutch Society of
      Family Physicians].

PMID- 9543792
TI  - [New proven materials, systems and technologies].

PMID- 9543793
TI  - [An introduction to forensic dentistry. Forensic dentistry can be defined as the
      dental discipline applied to the needs of justice].

PMID- 9543794
TI  - [The adventure that became reality].

PMID- 9543795
TI  - [Risk assessment--a tool to find the maximum safety?].

PMID- 9543796
TI  - [Sterilization--a re-evaluation?].

PMID- 9543797
TI  - [Current reproductive treatment].

PMID- 9543798
TI  - [Intracytoplasmic sperm injection].
AB  - The first results of intracytoplasmic sperm injection (ICSI) in Norway are
      presented. Acceptable fertilization rates were obtained for all indications;
      severe male infertility, as well as moderately reduced sperm quality where in
      vitro fertilization (IVF) and embryo transfer had previously failed. Furthermore,
      in cases where IVF had failed despite normal sperm quality, fertilization rates
      of 50-60% were achieved. The overall pregnancy rate was 24.9% per embryo
      transfer, and the live pregnancy rate per started cycle was 13.4%. As expected,
      the results improved with experience. The results were greatly influenced by the
      age of the female. In the age group 34 years or less, the total pregnancy rate
      per cycle was 32.4%, with a miscarriage rate of 24.2%. In the age group 35 years
      or more, (42% of the study group), the total pregnancy rate per embryo transfer
      was 15.2%, with a miscarriage rate of 75%. The corresponding implantation rates
      were 17.4% and 7.9% respectively. 23 children have been born so far, none with
      major malformations or chromosome abnormality symptoms.

PMID- 9543799
TI  - [Gabapentin--a new antiepileptic agent].
AB  - Gabapentin is a new antiepileptic drug. Its mechanism of action is not clearly
      understood, but it seems to differ from that of other antiepileptic drugs. The
      favourable pharmacokinetic properties of gabapentin make it simple to use. Our
      preliminary clinical observations with gabapentin at the National Center for
      Epilepsy are presented. 58 adult patients (mean age 28.9 years), mainly with
      refractory partial seizures, had gabapentin added to their existing medication.
      The follow-up period was 6.9 months on average. Only one patient experienced a
      reduction in seizures of more than 50%, while 25 patients experienced a moderate
      reduction in seizures (10-50%). The clinical effect was most favourable in
      patients with secondary generalized tonic-clonic seizures. Gabapentin was well
      tolerated, and no clinically significant interactions were encountered. Recent
      observations show that the doses of gabapentin used in our study may have been
      too low.

PMID- 9543800
TI  - [Cholecystectomy in the laparoscopic era].
AB  - Since 1991 laparoscopic cholecystectomy has been performed on 323 patients; 47
      patients underwent conversion to open surgery. In the same period, 46 patients
      were primarily selected for open cholecystectomy. Half the patients were operated
      on because of gallbladder colic (the sole symptom). Conversion to open operation
      (14%) occurred not so much because of peroperative complications, but rather
      because of anatomical problems. On the fourth postoperative day, one patient died
      of septicaemia caused by iatrogenic diathermy damage to the duodenum. One patient
      developed a stricture of the choledochus as a result of ischemia. This was caused
      by dissecting the choledochus, having mistaken it for the ductus cysticus which
      was missing in this anatomic variant.

PMID- 9543801
TI  - [Neonatal hemochromatosis].
AB  - Neonatal haemochromatosis is a disorder which affects foetuses and newborns. It
      is characterized by hepatocellular insufficiency, often appearing on the first
      day of life in the form of coagulopathy, hypoalbuminemia, hypoglycemia and
      jaundice. While spontaneous recovery has been reported, most of these infants
      die, and the diagnosis was previously often made during autopsy. With the help of
      MRI and salivary gland biopsies, plus increasing awareness of this disorder, the
      diagnosis is now often made quite early, and successful liver transplantations
      have been reported. Recently, there have also been encouraging preliminary
      reports of successful intervention with antioxidant and chelation
      pharmacotherapy, using a combination of selenium, vitamin E, N-acetylcysteine,
      deferoxamine, and prostaglandin E. We describe two patients with neonatal
      haemochromatosis who were both treated with this new "cocktail", one of whom died
      at five days of age, while the other survived, but needed a liver transplant at 2
      1/2 months of age. The pathology of this condition is characterized by hepatic
      cirrhosis with giant cell transformation, and by siderosis of extrahepatic
      tissues. The prognosis is poor, and our experience with antioxidant treatment has
      been disappointing. Liver transplantation is a therapeutic option, but its use is
      limited by the scarcity of donor organs and the small size of many of the
      patients.

PMID- 9543802
TI  - [Pregnancy, essential hypertension and chronic renal disease].
AB  - Women with chronic hypertension or renal disease are at a particular high risk of
      developing pre-eclampsia or eclampsia. Pre-eclampsia is associated with an
      increased risk of fetomaternal complications. In women with uncomplicated mild
      and moderate hypertension, pregnancy is usually normal. Treatment of high blood
      pressure aims at reducing maternal cardio- and cerebrovascular catastrophies, and
      the benefit of the treatment must be weighed against possible harmful effects on
      the foetus. In some cases, antihypertensive treatment can be discontinued, or
      medication changed. Preconceptional counselling is important both for women with
      chronic hypertension and, even more so, for women with renal disease, since the
      outcome of the pregnancy may be affected by the underlying disease.

PMID- 9543803
TI  - [Risk assessment in preventive medicine].
AB  - The aim of this article is to present and discuss the value of risk analysis in
      preventive medicine. Risk analysis consists of three major areas; risk
      assessment, risk management and risk communication. Risk analysis is illustrated
      here by two examples: exposure to radon and the risk of lung cancer, and
      infection with toxoplasma gondii in pregnancy and adverse pregnancy outcome. The
      analyses highlight the complementary elements of scientific judgement and
      political valuation. The barriers against implementation of preventive measures
      are many. Adequate risk assessment and consequence analysis based on empirical
      studies, together with risk communication are important for implementing the
      correct measures. We suggest that risk analysis should be used more often in
      medicine as a tool for systematic evaluation of the need and usefulness of
      preventive measures.

PMID- 9543804
TI  - [Compulsory collegial guidance. What do candidates in general practice think
      about training of practical procedures?].
AB  - In 1994 a new module addressing the quality of practical procedures was added to
      the Norwegian general practice specialisation programme. Over a five-year period
      31 practical procedures must be performed under the supervision of fellow GPs. In
      1995 a survey was carried out by questionnaire among all specialist candidates
      registered in the new programme (n = 165, response rate 83%) and a control group
      consisting of all candidates registered in 1993 (n = 162, response rate 62%). The
      aims of the survey were to evaluate the candidates' motivation, self-rated level
      of competence, and the presence of barriers to programme implementation. The main
      group and control group were almost identical; mean age has 36.5 years, 37% were
      females. There were no differences in the self-rated levels of competence between
      the groups. The majority (80%) reported a need to improve their performance of
      practical procedures, and 93% stated that mutual guidance with colleagues would
      be of considerable benefit by improving technical performance, professional
      confidence and the quality of relationships with colleagues. The main barriers to
      mutual guidance were shortage of time, lack of structured opportunities for
      performing procedures in the presence of colleagues, and lack of instruction
      manuals or videos detailing the correct performance of procedures.

PMID- 9543805
TI  - [Virtual reality in medical education].
AB  - Virtual reality technology has found new applications in industry over the last
      few years. Medical literature has for several years predicted a break-through in
      this technology for medical education. Although there is a great potential for
      this technology in medical education, there seems to be a wide gap between
      expectations and actual possibilities at present. State of the technology was
      explored by participation at the conference "Medicine meets virtual reality V"
      (San Diego Jan. 22-25 1997) and a visit to one of the leading laboratories on
      virtual reality in medical education. In this paper we introduce some of the
      basic terminology and technology, review some of the topics covered by the
      conference, and describe projects running in one of the leading laboratories on
      virtual reality technology for medical education. With this information in mind,
      we discuss potential applications of the current technology in medical education.
      Current virtual reality systems are judged to be too costly and their usefulness
      in education too limited for routine use in medical education.

PMID- 9543806
TI  - [Oslo '96--how is it?].
AB  - A new, problem-based integrated medical curriculum was introduced in Oslo in
      August 1996. We asked both students and teachers how satisfied they were with the
      first semester; teachers were also asked what their expectations were of the new
      curriculum. We investigated the relationship between the students' evaluation of
      individual elements of the curriculum and their satisfaction with the group
      tutors and the semester as a whole. During the course of the first semester
      students (n = 127), tutors (n = 26), and lecturers (n = 28) responded to
      questionnaires (response rates 92-100%) by rating various elements of the
      curriculum on a five point scale. Overall, the semester was rated either "good"
      or "very good" by 79% of the students and 91% of the teachers. The students'
      degree of satisfaction with the semester correlated with their evaluation of
      subject content, subject integration, and the case histories used in problem
      solving. The students' degree of satisfaction with the group tutors correlated
      with their evaluation of the tutors' contributions to subject content and group
      interaction and the tutors' personal attitudes. The tutors themselves expected
      the new curriculum to produce better results than the old one in all respects
      except the students' knowledge of basic science.

PMID- 9543807
TI  - [Group learning in medical education].
AB  - The implementation of group learning in medical education puts special demands on
      the participants, but also offers pedagogical benefits, which may be conductive
      to the efficient learning of facts, skills and attitudes. The group makes it
      possible to verify or modify the learned material, which is an important part of
      preparing for a career as a doctor. Students develop a dependence on others when
      solving problems in groups, whereas as clinicians they are often alone when
      confronted with problems demanding quick decisions. In this article we discuss
      some of the pedagogical principles involved in group learning and make
      suggestions on how to apply them to learning based on problem solving and other
      forms of group learning in the medical curriculum.

PMID- 9543808
TI  - [Teaching clinical decision making in Trondheim].
AB  - In the new medical curriculum at the University of Trondheim the preliminary
      teaching in clinical epidemiology is organized as a series of courses held in the
      third and fourth year. The objective is to develop skills in clinical appraisal
      based on scientific knowledge. A workbook and answers to exercises are provided
      for each course. The workbooks contain short introductions to important clinical
      epidemiological principles, as well as clinical problems which the students try
      to solve. The students' activities vary from reading to working with exercises
      and discussing the various topics. The courses give the students the opportunity
      to practice their newly acquired knowledge and to apply it to their clinical
      thinking.

PMID- 9543809
TI  - [Outplacement of medical students in local hospitals].
AB  - The organisation and content of the training of medical students in practical and
      clinical skills at Norwegian universities is presented and discussed. Based on
      experience from Tromso University, an increased use of local hospitals for
      training medical students in practical and clinical skills is planned for all
      universities in Norway.

PMID- 9543810
TI  - [Use of non-approved drugs].

PMID- 9543811
TI  - [Sick-listing practice of physicians--should the routines be changed?].

PMID- 9543812
TI  - [Massachusetts. Psychiatric rehabilitation and women's health].

PMID- 9543813
TI  - [Hemochromatosis--should genetic testing be a routine?].

PMID- 9543814
TI  - [Health and health services to the mentally disabled].

PMID- 9543815
TI  - [Standardization work in Norwegian medicine].

PMID- 9543816
TI  - [Means to measure patient satisfaction].

PMID- 9543817
TI  - [Feet--a diagnostic tool?].

PMID- 9543818
TI  - [Etidronate versus alendronate].

PMID- 9543819
TI  - [Controlled release of pseudoephedrine HCl from pellets].
AB  - This study describes the development work on a dosage form, which should release
      the drug pseudoephedrine HCl over twelve hours. Pellets were chosen as the dosage
      form. The pellets contained 20, respectively, 45 percent pseudoephedrine HCL and
      were produced using a high shear mixer-granulator. These pellets were coated in a
      fluidized bed and in a high shear mixer-granulator equipped with a microwave
      drying installation. The results of the experiments indicate that it is possible
      to produce pellets in a high shear mixer-granulator. Strong pellets with a narrow
      size distribution were obtained. A high shear mixer-granulator appears,
      therefore, to be a valuable alternative to the more commonly used pellet-forming
      technique of extrusion-sphere formation. The pellets could be coated as well in a
      fluidized bed as in a high shear mixer-granulator equipped with a microwave
      drying installation. A major advantage of the high shear mixer-granulator
      equipped with a microwave drying installation is the possibility to perform
      several unit operations such as mixing, pellet formation drying, and coating in
      one piece of equipment. With respect to the requirement of getting a release of
      pseudoephedrine HCl over twelve hours, the pellets containing 20 percent
      pseudoephedrine HCl fulfilled this requirement. For pellets containing 45 percent
      pseudoephedrine HCl it appears to be hard to obtain a sufficient delay in release
      using the commonly used coating formulations. This can be attributed to the very
      good solubility of pseudoephedrine HCl in water. Optimization of the coating
      formulation by changing the nature and concentration of the plasticizer may solve
      the problem.

PMID- 9543820
TI  - On the roles of extracellular matrix remodeling by gelatinase B.
AB  - Human extracellular matrix is constantly remodelled by de novo synthesis of
      structural components and by degradation of the matrix proteins by various
      proteinases. The secreted proteolytic enzymes are regulated at several levels: by
      control of gene transcription, by glycosylation, by specific inhibitors and by
      enzyme activation processes. The latter level most often involves clipping of a
      proenzyme or zymogen into an active proteinase. A series of such activation
      reactions leads to enzyme cascades. Whereas proteolytic activation is an all-or
      none phenomenon, glycosylation usually has a restricted or fine-tuning effect on
      the catalytic activity of enzymes. Commonly, a two- to threefold reduction in
      specific activity is imposed by N-glycosylation on each member of the multi
      enzyme chain. In a series comprising e.g. four enzymes, this can lead to
      significant influences (2(4)-3(4)-fold increase) on the substrate converting
      activity of the terminal member of a cascade. Gelatinase B is a terminal member
      of the protease cascade which leads to matrix degradation. It cleaves gelatins
      (denatured collagens or collagen fragments after digestion by collagenase) and
      other substrates and is thought to be involved in matrix remodeling during the
      normal processes of embryogenesis, tissue remodeling and development. Gelatinase
      B expression is upregulated in pathological states such as invasion of cancer
      cells and when leukocytes are released from the bone marrow and migrate towards
      an inflammatory focus. Proteases, including gelatinase B, are transcriptionally
      regulated by cytokines and directly by the activation processes. The gene
      regulation of enzyme inhibitors as well as other humoral factors, which
      contribute to protease activation, influence protease activities in an indirect
      way. Proteases might also play a role in the pathophysiology of chronic
      inflammation and autoimmunity by cleaving extracellular structural proteins and
      by generating proteolytic fragments. Indeed, these remnant fragments
      antigenically resemble the original precursor proteins, but are structurally and
      quantitatively different and may provoke an autoimmune response. Application of
      the knowledge of the structure, function and regulation of gelatinase B has
      contributed to the understanding of the mechanism of action of some gelatinase
      inhibiting antirheumatic drugs and promises to contribute further to the
      development of novel treatment strategies for autoimmune diseases such as
      multiple sclerosis and for invasive cancers.

PMID- 9543821
TI  - Acute phase proteins as protective factors against the toxicity of tumor necrosis
      factor.
AB  - Tumor Necrosis Factor is an endogenous messenger molecule (cytokine) exhibiting a
      broad range of biological activities. Of special interest is its cytotoxic
      activity, specific for transformed tumor cells and which results in outspoken
      tumor regression in experimental animals. Administration of high dose of TNF,
      necessary to treat internal tumors, however is currently impossible because of
      the pro-inflammatory properties of TNF. Injection of TNF causes significant
      decrease in blood pressure and serious liver-toxicity. However, the liver is not
      only a target organ for TNF, it also produces protecting factors. Based on our
      studies of the role of Interleukin-1 and Interleukin-6, two other cytokines, we
      investigated the protective role of a set of liver-derived proteins, the acute
      phase proteins. We identified two such proteins as protective factors in our
      mouse models: alpha-1-Acid Glycoprotein (AGP) and alpha-1-Antitrypsin (AT). Both
      proteins confer complete protection against TNF-induced lethality in mouse
      models, and are currently evaluated as adjuvans in TNF-based antitumor therapy.
      The protection by both proteins also brought us new insights in the mechanism of
      TNF-induced liver-toxicity. In this sense, molecules like elastase and Platelet
      Activating Factor were recognized as mediating factors.

PMID- 9543822
TI  - [Hypersensitivity following low one-time irradiation dosage and induced radio
      resistance].
AB  - There is now little doubt of the existence of radioprotective mechanisms, or
      stress responses, that are upregulated in response to exposure with small doses
      of ionizing radiation and other DNA-damaging agents. Phenomenologically, there
      are two ways in which these induced mechanisms operate. First, a small
      conditioning dose (generally below 30 cGy) may protect against a subsequent,
      separate irradiation. This has been termed the adaptive response. Second, the
      response to single doses may itself be dose-dependent so that small acute
      radiation exposures are more effective per unit dose than larger exposures above
      the threshold where the induced radioprotection is triggered. This combination
      has been termed low dose hypersensitivity (HRS) and induced radioresistance (IRR)
      as the dose increases. Both the adaptive response and HRS/IRR have been well
      documented in studies with yeast, bacteria, protozoa, algae, higher plant cells,
      insect cells, mammalian and human cells in vitro, and in studies on animal models
      in vivo. There is indirect evidence that the adaptive response and the IRR
      phenomenon in response to single doses is a manifestation of the same underlying
      mechanisms, namely an increase of the amount and rate of DNA repair induced by
      low radiation doses.

PMID- 9543823
TI  - Some facts about the supply of dental hygienists.

PMID- 9543825
TI  - Modern management of dental caries: the cutting edge is not the dental bur.

PMID- 9543824
TI  - A brief review of the newer nonsteroidal anti-inflammatory analgesics.
AB  - The intent of this article is to present information about selected analgesic
      products marketed within the past five years and their potential for use in
      dental practice. As a rule, most new drugs are not specifically produced for
      dental therapy as economics and medical needs drive research and development.
      However, for this group of drugs, the dental pain model involving third molar
      extractions has provided some of the clinical data. Because the information
      presented is brief, the practitioner is cautioned to consult complete prescribing
      information, such as the drug package insert, prior to using of any medication
      which might be appropriate to employ in the usual course of dental therapeutics.

PMID- 9543826
TI  - DOS, Windows, networks and more!

PMID- 9543827
TI  - The amalgam issue ... or is it?

PMID- 9543828
TI  - Practicing the principles of gingival non-violence in restorative dentistry.

PMID- 9543829
TI  - Ten year results of sealants placed in the New Mexico sealant program.

PMID- 9543830
TI  - The handpiece issue.

PMID- 9543831
TI  - Subepithelial connective tissue grafts.

PMID- 9543832
TI  - The black hole--what happens to your insurance preestimates.

PMID- 9543833
TI  - The functional smile: a goal for orthodontics.

PMID- 9543834
TI  - Elements of a beautiful smile.

PMID- 9543835
TI  - Prevention of post-operative sensitivity in bonded restorations.

PMID- 9543836
TI  - Supportive periodontal care. A review of the literature.

PMID- 9543837
TI  - Stress and dentistry. Better practice through control.

PMID- 9543838
TI  - Health providers in rural New Mexico.

PMID- 9543839
TI  - So you thought you knew how to take an alginate impression OR can it really be
      done without gagging?

PMID- 9543840
TI  - Current trends in periodontal regeneration: a review and case report.

PMID- 9543841
TI  - Selection of dental hygiene as a career: associate degree students compared with
      baccalaureate students.
AB  - One of the most significant issues in the dental hygiene profession is the
      recruitment of qualified applicants. Throughout the decade of the 80s, a dramatic
      decline in enrollment has occurred in dental hygiene programs across the nation.
      According to recent demographic reports, there are fewer individuals in the age
      group where dental hygiene students are traditionally recruited and no
      significant change is expected. Therefore, in order to maintain and improve the
      pool of students preparing for a career in dental hygiene, it is critical that an
      attempt be made to understand the forces which lead students to choose the health
      care profession. A study was conducted using baccalaureate alumni and three
      classes in the baccalaureate degree dental hygiene program at The Ohio State
      University in order to determine why they had chosen the career of dental
      hygiene. This study was subsequently expanded to include students enrolled in
      eight associate degree dental hygiene programs in Ohio. The results from the
      survey indicate that career decisions are made at varying points in the
      educational process. Dentists and dental hygienists account for half of the
      influence in the decision process with high school guidance counselors having
      negligible influence. Nearly all respondents chose working with people as the top
      career benefit. Those findings point to the importance of involving dental and
      dental hygiene professionals in the recruitment process and the necessity to
      provide appropriate information to others who may provide career counseling.

PMID- 9543842
TI  - Treatment of an unusual case of external resorption and a six-year follow-up of
      that treatment.
AB  - It seems that few cases of idiopathic external resorption appear in the
      literature and fewer that are followed for a number of years. Such a case is
      presented with a six-year follow-up. Results showed that there was no remaining
      pathology and that the tooth was completely asymptomatic following its initial
      treatment.

PMID- 9543843
TI  - Relationships between dental hygienists' career attitudes and their retention of
      practice. Part II. From the results of the Ohio Dentist and Dental Hygiene
      Surveys.
AB  - This article utilizes findings from the Ohio Dental Hygiene Survey and Ohio
      Dentist Survey to uncover what specific dental hygiene attitudes exist relative
      to employment and what factors have led to job termination and to re-entry. Ohio
      dental hygiene employees are most satisfied with patient relationships, co-worker
      relationships, and flexible working hours. The dental hygienists are least
      satisfied with fringe benefits, financial growth, and career creativity. Salary,
      benefits, nor career longevity were significant factors in determining
      satisfaction. Dental hygienists who were not working when surveyed, said they
      would consider returning to practice if a better salary were available, if they
      could find part-time work, if there were a good wage scale with benefits, or if
      their own financial need changed. Thirty-six percent of the non-practitioners
      said they would not ever consider returning to practice due to working
      conditions, establishment of a new career, or inadequate compensation. Dentist
      employers stated that they were satisfied or very satisfied with their dental
      hygienists' patient care and contribution to the practice.

PMID- 9543844
TI  - Poverty, health insurance, and use of health services.

PMID- 9543845
TI  - An analysis of dental hygienist remuneration. Part III. From the results of the
      Ohio Dentist and Dental Hygiene Surveys.
AB  - The Division of Dental Hygiene of Ohio State University, working under a grant
      from the Ohio Dental Association, completed research defining the practice of
      dental hygiene in Ohio utilizing data gathered in the summer of 1991. This
      portion of the research focuses on the salaries and benefits earned by practicing
      Ohio dental hygienists. It also presents the salary and benefit levels which Ohio
      dentists believe to be reasonable for dental hygienist employees. The largest
      number of dental hygienists work 27 hours per week and are paid a straight salary
      averaging $15.86 per hour. The largest number of dentists believe that
      experienced, full-time dental hygienists should receive higher salaries and more
      benefits than part-time hygienists. They feel that $16-$21 per hour is a
      reasonable salary, and they most often provide reduced dental fees as a benefit.

PMID- 9543846
TI  - Comparison of handpiece asepsis among Ohio dentists: 1991 & 1992.
AB  - In 1991, we found that 23 percent of Ohio dentists sterilized handpieces between
      patients and 67 percent flushed handpieces between patients. In this study, we
      chose to investigate the changes in handpiece asepsis within Ohio dental offices
      for the twelve-month period ending August, 1992. Sixty-two percent of the 730
      offices polled responded to the questionnaire. Offices reporting sterilization of
      handpieces between patients in 1992 is 80 percent compared to 23 percent in 1991.
      Sixty-nine percent of offices in the 1992 survey reported that they have changed
      infection control protocol to include heat sterilization of handpieces between
      patients while 24 percent report disinfection between patients. Back order of
      equipment, inadequate number of handpieces and fear of damage is cited by the
      offices using disinfection as the reasons for not sterilizing handpieces.
      Flushing handpieces between patients is reported by 83 percent of the offices.
      Previously, only 67 percent flushed between patients. Anti-retraction valves are
      present in 69 percent of the water lines. Breakdown of handpieces attributed to
      sterilization was reported by 45 percent of the offices. Two-hundred and three
      offices (45 percent) report questions from patients regarding office infection
      control policies. Infection control awareness of the general population and
      implementation of these procedures by dental professionals is increasing in Ohio.

PMID- 9543847
TI  - Dentally induced bacteremia and infection of total joint replacement
      arthroplasty.

PMID- 9543848
TI  - Straight talk on Dental Corps career planning.

PMID- 9543849
TI  - AIDS-related knowledge, attitudes, and behavior among Navy personnel.

PMID- 9543850
TI  - A denture for Tojo.

PMID- 9543851
TI  - U.S. Navy Dental Corps Survey of 1994: analysis of narrative responses.

PMID- 9543853
TI  - Aesthetic dentistry systems: positioning advanced materials in a modern dental
      practice.

PMID- 9543852
TI  - Fiber-reinforced framework and Ceromer restorations: a technical review.
AB  - The utilization of synthetic resins and ceramics in combination with metal
      frameworks continues to be the mainstay of crown and bridge prosthetics. Although
      most of these systems have resulted in years of clinical success, each material
      when used in combination has inherent properties that induce stresses to the
      system. The combination of ceramic technology and polymer research, in addition
      to fiber integration, has resulted in the development and introduction of a new
      category of crown and bridge materials--a ceromer and fiber-reinforced
      restorative system. This article examines the history of polymer and ceramic
      technology, and reports the clinical and research data currently available on one
      indirect ceromer system (Targis System, Ivoclar Williams, Amherst, NY).

PMID- 9543854
TI  - Anatomical applications of a new direct Ceromer.
AB  - Composite resin materials have become the basic restorative materials of the
      modern aesthetics-oriented practice. However, the application of composite resin
      in posterior teeth remains a challenge as a result of its handling
      characteristics and chairside stratification. New ceramic optimized polymers
      (ceromers), such as Tetric Ceram (Ivoclar Vivadent, Amherst, NY), now offer
      versatility and improved handling properties in response to increasing clinical
      demand for producing high-quality natural restorations. With a well-designed
      instrumentation, the work of the clinician may be greatly facilitated. This
      article evaluates the selection and utilization of a direct ceromer material for
      posterior restorations and presents a predictable method to achieve aesthetic
      restorations.

PMID- 9543856
TI  - Postorthodontic restoration of enamel surface characteristics.
AB  - Following orthodontic treatment, the mechanical debonding of brackets often
      results in damage to the enamel surface of teeth. Loss of natural luster, a
      roughened surface, and scarring may occur. When scarring occurs, a method for re
      establishing the enamel luster and surface characteristics can be instituted by
      either the restorative dentist or the orthodontist. One method of restoring
      enamel luster and natural surface characteristics following removal of
      orthodontic fixtures is through a sequence of enamel polishing. This article
      discusses logical steps for the restoration of enamel through the utilization of
      polishing burs and progressive pastes (Proxyt), Ivoclar Vivadent, Amherst, NY)
      for the final aesthetic orthodontic result.

PMID- 9543855
TI  - Achieving functional restorations utilizing a new Ceromer system.
AB  - The advent of pressed ceramic restorations (IPS Empress, Ivoclar Williams,
      Amherst, NY) has driven dental therapy to continuously strive for more aesthetic
      and functional materials. The dental profession requires restorations to exhibit
      strength, natural color, wear resistance, marginal integrity, and ease of
      fabrication in the restorative therapies selected. With the introduction of a new
      ceromer and fiber-reinforced composite (FRC) system (Targis System, Ivoclar
      Williams, Amherst, NY), the replacement of a single tooth or multiple teeth with
      a FRC, metal-free bridge is now a suitable alternative to conventional dental
      therapy. This presentation will review the clinical protocol, material
      properties, and aesthetic characteristics of this new generation of restorative
      material.

PMID- 9543857
TI  - Introducing a new brick onto a solid foundation.

PMID- 9543858
TI  - Increasing patient satisfaction with natural denture teeth.
AB  - Successful laboratory communication in removable prosthodontics will always be
      more complex than in fixed prosthodontics. However, the unique characteristics of
      natural denture teeth (SR-Antaris/SR-Postaris), Ivoclar Williams, Amherst, NY)
      are enabling clinicians to overcome functional and aesthetic challenges.
      Specifically, the characterized anatomy of these anterior and posterior teeth,
      and their translucency and natural layering, facilitate the reestablishment of a
      natural smile. This article describes the benefits of SR-Antaris/SR-Postaris
      denture teeth and provides guidelines for communication with the laboratory to
      ensure predictable results.

PMID- 9543859
TI  - Classification and application of cementation alternatives.
AB  - More important than any resin cement is the marginal fit and retentive nature of
      the ceramic restoration to be bonded. Cementation should not be intended to
      compensate for poor dentistry, but to assist in producing superior aesthetic
      results. Responding to the demand for all-ceramic restorations, dental
      manufacturers continue to refine the resin cements used in luting for this
      modality. The ideal resin cement for ceramic restorations must demonstrate low
      viscosity; easy loading; a film thickness which facilitates complete seating high
      strength; and excellent wear resistance. This article reviews the available resin
      cements, with particular focus on a new type of initiator and stabilizer for
      light- and dual-cured resin cements.

PMID- 9543860
TI  - Technique for realistic anterior crowns using the IPS Empress porcelain system.
AB  - In dentistry, the concept of realism can be applied to the creation of an
      artificial prosthesis that is not perfect, but real. If prosthesis are made to a
      flawless perfection, they will appear artificial. Ultimately, the clinician and
      ceramist should strive for realism. The IPS Empress System (Ivoclar Williams,
      Amherst, NY) is an all-ceramic restorative alternative utilizing a pressable
      leucite-reinforced glass ceramic for a variety of indications (e.g., crowns,
      inlays/onlays, veneers). The resulting tooth-colored and metal-free restorations
      combine strength and aesthetics approaching those of natural teeth. This article
      describes the technique and procedures required to achieve realistic anterior
      crowns with this all-ceramic system.

PMID- 9543861
TI  - The changing face of aesthetic dentistry.

PMID- 9543863
TI  - Anecdotal, clinical evaluation: a catalyst for the evolution of dentistry.

PMID- 9543862
TI  - Securing the position of ceramic veneers in dentistry.
AB  - Porcelain laminate veneers have exhibited predictability and, as a result,
      experienced an incredibly rapid public acceptance with widespread utilization.
      The introduction of a stronger, leucite-reinforced ceramic system which could be
      accurately pressed (IPS Empress, Ivoclar Williams, Amherst, NY), presented new
      avenues for this remarkable treatment modality beyond aesthetic enhancement.
      Porcelain veneer restorations could be utilized to accurately alter and correct
      occlusal relationships, and the less abrasive surface of the material offered a
      distinct advantage in occlusal modifications, such as altering cuspal guidance or
      vertical dimension. This presentation reviews the history of porcelain veneer
      restoration and outlines the use of a luting cement (Variolink II, Ivoclar
      Vivadent, Amherst, NY) for its application.

PMID- 9543864
TI  - Ceromer/FRC technology: the future of biofunctional adhesive aesthetic dentistry.
AB  - With recent advancements in adhesive technology, restorative materials have
      evolved to an enhanced level of aesthetics while enabling more conservative
      cavity preparations and promoting reinforcement of the remaining tooth structure.
      These restorations have included both anterior and posterior treatment modalities
      applied directly and indirectly. With a growing awareness on the part of many
      patients of the possible cosmetic treatment alternatives came the desire for
      aesthetic, metal-free, durable restorations. This presentation discusses the
      material properties and clinical protocol of a new material which combines a
      ceramic optimized polymer with a fiber-reinforced framework for durable,
      aesthetic anterior and posterior restorations.

PMID- 9543865
TI  - Direct Ceromers: assuring restorative integrity with selective application of two
      viscosities.
AB  - The objectives of an ideal direct restoration include pulpal health,
      biocompatibility, occlusal stability, anatomical restitution, marginal
      perfection, and interproximal integrity. While tooth-colored composites have
      replaced amalgam as the restorative material of choice for many dental
      professionals, the utilization of composite materials of two different
      viscosities has proven effective in increasing strength and adaptation, and
      facilitating placement of anterior and posterior restorations. Several newly
      enhanced composite combinations have begun to allay reservations about directly
      placed tooth-colored restorations. This article classifies the ideal handling
      characteristics and benefits of a recently introduced, direct Ceromer system
      (Tetric Flow and Tetric Ceram, Ivoclar Vivadent, Amherst, NY.)

PMID- 9543866
TI  - Conventional cementation technique for Targis restorations.
AB  - Ivoclar can now recommend a clinical and laboratory procedure for the
      conventional cementation of Targis single- and multiple-unit full-coverage
      restorations. The ability to bond restorations utilizing enamel/dentin bonding
      systems and dual-cure resin cements (Variolink II, Ivoclar Vivadent, Amherst, NY)
      has minimized microleakage and postoperative sensitivity, provided stronger
      restorations, and reinforced remaining tooth structure. Unfortunately, the
      benefits of the adhesive technique can often be compromised by existing or pre
      existing clinical conditions. This challenge has limited the broad use of
      adhesive, metal-free restorations in many clinical situations. Targis
      restorations can now be successfully cemented utilizing zinc phosphate or
      conventional glass ionomer cements. This article describes the technique through
      a case presentation.

PMID- 9543867
TI  - IPS Empress: a standard of excellence.
AB  - For 10 years, clinicians have been able to provide patients with a proven
      aesthetic and functional restoration that exhibits wear-compatibility,
      durability, and marginal integrity. This leucite-reinforced, pressed ceramic (IPS
      Empress, Ivoclar Williams, Amherst, NY) presents to patients and dentists the
      option of a metal-free alternative which retains the functional advantages of a
      porcelain-fused-to-metal restoration. This article illustrates the importance of
      sound laboratory communication in the utilization of this restorative material,
      focusing upon three aspects: midline and incisal edge inclination, elimination of
      open gingival embrasures, and incisal edge translucency. Techniques are also
      presented in order to efficiently communicate details of each case presented to
      the laboratory.

PMID- 9543868
TI  - Life on the arc: principle-centered comprehensive care.
AB  - Today's dental practice is experiencing an evolution in the manner through which
      new materials and techniques are marketed and introduced. An increasing concern
      among the patient population regarding aesthetics contributes to the acceptance
      of a commodity dental philosophy, without questioning the reliability of the
      technique or new material. A principle-centered practice differentiates the
      product marketing from the viability of a restorative material in vivo. This
      article discusses the concept of a principle-centered practice and describes how
      to place quality products in a balanced system in which harmony exits between all
      components of the masticatory system: the teeth, the muscles, and the
      temporomandibular joints.

PMID- 9543869
TI  - An innovative approach to Class II preparation and restoration.
AB  - When patients exhibit Class II defects requiring restoration, the treatment
      modality and respective preparation requirements may present challenges to the
      clinician. Aesthetics, chairside time, and expense become factors for the
      consideration of both dentist and patient. However, a new sonically driven system
      for the preparation and restoration of proximal defects was recently introduced
      (SONICSYS, Ivoclar Vivadent, Amherst, NY). This system, composed of diamond
      coated tips and prefabricated ceramic inserts, promises to enable clinicians to
      efficiently, confidently, and expertly prepare and restore Class II defects in a
      timely, consistent, and cost-efficient manner. This article describes the
      components of the system and demonstrates its utilization in a case report.

PMID- 9543870
TI  - An aesthetically and physically advanced system for post and core restorations.

PMID- 9543871
TI  - All-ceramic crown systems: clinical research versus observation in supporting
      claims.

PMID- 9543872
TI  - Restoration of a single anterior crown.
AB  - All-ceramic restorations have gained patient acceptance and are increasingly
      being used in aesthetic appearance-related restorations. This case report of a
      single anterior crown matching natural dentition utilizes some of the new special
      effect ceramic powders designed for use with the layering technique. These
      powders help to properly replicate incisal, mamelon, and gingival areas. The
      clinical procedure is described, using photographs of the case to illustrate the
      steps involved.

PMID- 9543873
TI  - Six years of clinical experience with an all-ceramic system.
AB  - The search for tooth-colored and metal-free restorations is one of the major
      challenges in dental research. For several decades, ceramic has been used as a
      restorative material because of its aesthetics and stability. Unfortunately, the
      survival rate of most all-ceramic systems seems unsatisfactory; due to the
      natural brittleness of ceramic, fractures have been the primary reason for the
      high failure rate. Since 1988, the University of Zurich Dental School,
      Switzerland, has been working with the IPS Empress all-ceramic system
      (Ivoclar/Williams, Amherst, NY). This article reports the clinical and research
      data from approximately 3,000 all-ceramic restorations.

PMID- 9543874
TI  - A clinical trial of all-ceramic crown restorations: status, fall 1995.
AB  - Although porcelain-fused-to-metal (PFM) restorations are the most widely used
      full-coverage crown restoration systems, their inherent properties make the
      achievement of natural aesthetic restorations an elusive task. In contrast, the
      all-ceramic system (IPS Empress, Ivoclar North America, Amherst, NY) offers
      excellent translucency and vitality, without the opacity associated with PFM
      restorations. Its vitality is further enhanced by an adhesive resin cementation
      method that conducts the color of the underlying tooth structure. This article
      reports the status of a 5-year investigation, initiated in 1992, of the clinical
      performance of the IPS Empress all-ceramic system and the resin cementation
      system used with it.

PMID- 9543876
TI  - Personal and career management.

PMID- 9543875
TI  - IPS Empress veneers. Color communication, laboratory fabrication, and
      cementation.
AB  - Once considered to be revolutionary, porcelain veneers are now the foundation of
      most aesthetic dental practices. Requiring only conservative preparations,
      porcelain veneers can dramatically change a smile. This article discusses the
      technique necessary to prepare and place porcelain veneers, using a new pressed
      ceramic system. Close and thorough cooperation and communication between the
      clinician and the laboratory are essential throughout the procedure, and this
      article is coauthored by a dentist and a ceramist.

PMID- 9543877
TI  - Career development: the key questions.

PMID- 9543879
TI  - Presentation of self: being heard.
AB  - "Be yourself and you'll be fine." Sound advice but not so easy to achieve in
      pressure situations. How does one project oneself effectively? This article
      discusses ways to stop selling oneself short and to be heard.

PMID- 9543878
TI  - Personal development: a lifelong journey.
AB  - This article explores critical aspects of career and personal development, in
      particular the importance of a lifelong commitment to reflective practice. It
      focuses on the key questions: Where have I been? Where am I now? and Where do I
      want to be? Specific approaches discussed include journal writing and collegial
      small group work.

PMID- 9543880
TI  - Is your financial house in order?
AB  - In today's rapidly changing world individuals are being faced by many new issues
      that are challenging their ability to survive financially. It is therefore
      important that we recognize the need to manage our financial lives. To do that
      requires a commitment of time to identify assets held and determine how best to
      protect them, set future financial goals, and then determine how assets can be
      used to reach those goals.

PMID- 9543881
TI  - Strength of character through the ethics of nursing.
AB  - "A Practice-Based Bioethic" is a regular column in Advanced Practice Nursing
      Quarterly. A practice-based approach is derived from, and therefore is intended
      to be appropriate to, the situation of a patient, the purpose of the health care
      setting, and the role of the nurse. It is based on a shared state of awareness,
      the foundation on which ethical interactions between nurse and patient occur.

PMID- 9543882
TI  - Career journeys.
AB  - Capturing stories of a culture is important to its life blood. The following
      career stories of a sample of our colleagues describe the many and interesting
      journeys to advanced practice roles they have explored through their careers.

PMID- 9543883
TI  - A reflective approach to career trajectory in advanced practice nursing.
AB  - Opportunities in nursing continue to expand. Advanced practice nurses today have
      greater control over the scope of their practice and can look forward to mapping
      a career pathway using personal and professional talents and interests. This
      article offers a reflective process approach to evaluating and relating career
      satisfaction and satisfactoriness to personal development needs. Through
      implementation of the suggested reflective exercise, a 3- to 5-year career plan
      can be constructed that will guide change and affect growth for the advanced
      practice nurse.

PMID- 9543884
TI  - Clinical leadership.
AB  - Leadership skills are necessary no matter what work you are doing. This article
      explores some controversial aspects of leadership for clinical professionals.

PMID- 9543885
TI  - Crystal ball gazing: back to the future.
AB  - This article presents some of the challenges, competencies, and opportunities
      that advanced practice nurses will face in the near future as the emerging health
      care system unfolds. Nurses must be knowledgeable about, prepared for, and
      participate in the creation of a preferred future in health care policy and
      practice. Advancing educational programs and orienting research and activism in
      the direction of personal and community health will allow advanced practice
      nurses to continue to have a significant influence on the transformation of
      health care and delivery systems.

PMID- 9543886
TI  - An interview with Judith Igoe. Interview by Cheryl Slagle King.

PMID- 9543887
TI  - Autonomy in practice: are nurse practitioner students being prepared for reality?
AB  - This article reports on a study examining the relationship between nurse
      practitioner students' expectations of future professional autonomy and the level
      of autonomy experienced by certified nurse practitioners. The findings indicate
      that practicing nurse practitioners experience a greater sense of autonomy than
      student nurse practitioners perceive. As autonomy is an issue of continuing
      importance in nursing, and for advanced practice, further research is needed to
      assist schools of nursing in devising reality-based curricula for nurse
      practitioner programs.

PMID- 9543888
TI  - Cross-jurisdictional advocacy in family violence: the role of the advanced
      practice nurse in the judicial system.
AB  - Advanced practice nurses have many career alternatives. The role of the advanced
      practice nurse in the judicial system is as a cross-jurisdictional advocate--a
      case manager, a court advocate, and a legal nurse consultant. This article
      explores these roles with specific emphasis to the problem of family violence.

PMID- 9543889
TI  - Nurses can influence public health policy.
AB  - Nurses can and should take part in making the policy decisions that affect their
      practice and the health of their clients. This article provides some common-sense
      tips for organizing collaboratively in order to make changes that count.

PMID- 9543890
TI  - Giving something back.
AB  - The Taoist teachings of self-reflection, openness, and sharing of self illustrate
      the need for the seasoned professional to examine one's own practice and share
      with the greater professional community. Taoism incorporates interdependency and
      harmony for all systems and suggests that as individuals we rely on the well
      being of the whole. Four specific methods provide meaningful ways to give back to
      the profession; networking, presenting, publishing, and professional association
      work. Implementing one or more of these methods promotes the profession's
      collegial spirit and facilitates one's own growth while giving to others.

PMID- 9543891
TI  - Your career and job success.

PMID- 9543892
TI  - From job to career: are you ready?
AB  - The times call for a focus on career not on job. Nurses will advance to the
      extent they can match their skill sets with the demands of the new age of health
      care.

PMID- 9543893
TI  - Surprising findings? ... I don't think so.

PMID- 9543894
TI  - Despite the continuum of care, is hospice terminal?

PMID- 9543895
TI  - Comfort and incidence of abnormal serum sodium, BUN, creatinine and osmolality in
      dehydration of terminal illness.
AB  - This prospective clinical study was undertaken to evaluate the effect of
      spontaneous food/fluid intake on serum sodium and comfort levels in a population
      of terminal patients (n = 31) receiving clysis or intravenous hydration. The
      median and mode of serum sodium were within normal limits and 56 percent of the
      patients were eunatremic. There was no statistically significant difference in
      comfort scores between predehydration and dehydration phases, and 85 percent had
      an optimal comfort score. A statistically significant difference was found (p <
      0.5) between mean daily comfort scores of those with normal sodium versus those
      with abnormal sodium; those with hypernatremia were lower but still in the top
      third comfort levels. Because the sodium was tested using a Chem7, we also were
      able to calculate the BUN, creatinine, and osmolality. These are presented and
      compared to other study results. The findings of this study reinforce the belief
      that fluid depletion in dying patients results in relatively benign symptoms,
      that serum sodium levels are not always altered with limited intake and that
      comfort levels can be maintained when the serum sodium is abnormal.

PMID- 9543896
TI  - First know thyself ... the value of a hospice environmental analysis.

PMID- 9543897
TI  - Palliative chemotherapy.

PMID- 9543898
TI  - Barriers to effective pain/symptom control.
AB  - We have a challenging call to provide compassionate care and comfort in a
      changing and varied clinical, social and financial setting. Multiple variables
      including race, creed, age, and sex of the patient can impact the decision-making
      process. It is hoped that consideration by professional caregivers of the above
      barriers will improve and provide consistent care to those put in our charge.

PMID- 9543899
TI  - Palliation of painful bone metastases: Strontium-89.
AB  - Most patients with bony metastases experience painful symptoms. Strontium-89
      isotope therapy is an alternative to traditional hemibody radiation in cases of
      multiple, diffuse metastases. Generally given as a single i.v. slow-push
      infusion, relief begins in one to three weeks, peaks at six weeks, and has a mean
      duration of 12 months. Up to 22 percent of patients are pain-free at three
      months.

PMID- 9543900
TI  - Onchologic stress: its causality in myofascial pain disorder or in
      temporomandibular disorder.

PMID- 9543901
TI  - Hospice or palliative care?

PMID- 9543902
TI  - What is your role? You can make a difference!

PMID- 9543903
TI  - Preventing amputations in patients with end stage renal disease: whatever
      happened to foot care?
AB  - Lower extremity amputations in patients with diabetes are largely preventable
      through proper foot hygiene, routine foot surveillance, and patient education
      about proper foot care. Diabetics with end stage renal disease are at especially
      high risk for foot complications, but nephrology nursing has been largely silent
      about the importance of diabetic foot care. This article discusses the diabetic
      pathophysiology underlying the development of most foot complications and
      outlines the basic principles of safe and effective foot care.

PMID- 9543904
TI  - Osteitis fibrosa: treatment trends.
AB  - Renal osteodystrophy is frequently seen in patients with end stage renal disease.
      Osteitis fibrosa associated with secondary hyperparathyroidism is often
      diagnosed. Treatment options vary based on disease severity. Individual patient
      considerations need to be addressed to determine the best therapeutic plan.
      Medical management with calcitriol, dietary modifications, and administration of
      phosphate binders continues to be the best treatment for most patients.
      Parathyroidectomy should be reserved for patients with complications related to
      severe irreversible hyperparathyroidism and/or failure of medical management.
      Total resection of all parathyroid tissue with or without autotransplant is the
      most common surgery for hyperparathyroid bone disease.

PMID- 9543905
TI  - Teaching program effects on high phosphorus levels in patients receiving
      hemodialysis.
AB  - OBJECTIVE: The objective was to determine the effect of a patient education
      intervention on decreasing serum phosphorus levels, increasing calcium levels,
      and increasing knowledge in hemodialysis patients with abnormally high phosphorus
      levels (n = 29). SAMPLE/SETTING: Study subjects were (a) on hemodialysis at least
      3 months, (b) English speaking, (c) mentally alert, (d) not under constant
      nursing care, and (e) hyperphosphatemic. The study was conducted at two suburban
      dialysis units in the Chicago Metropolitan area. DESIGN: This study had a one
      group, pretest-posttest design, using subjects as their own controls. METHODS:
      The intervention was a one-on-one education session performed by a nephrology
      nurse using a teaching booklet, an Osteodystrophy Tool, and a medication diary.
      RESULTS: The mean change score for phosphorus did not reach significance (t [28]
      = .68, p = .50). The change in mean phosphorus levels was not related to gender,
      education, or dialysis unit. There was a weak relationship between a decrease in
      phosphorus and an increase in knowledge about phosphorus (r = 0.21). However,
      calcium levels improved significantly after the teaching intervention (t [28] =
      3.23, p = 0.003). Mean overall scores for knowledge about phosphorus control
      increased significantly also (t [28] = 2.60, p = < 0.01). CONCLUSION: The
      findings of this study demonstrated that an education session can have an effect
      on patients' knowledge and compliance.

PMID- 9543907
TI  - Medication compliance and the older hemodialysis patient.
AB  - OBJECTIVE: The purpose of this study was to identify relationships between
      demographic factors, psychosocial characteristics, and medication compliance
      rates in older patients receiving hemodialysis and to determine the effectiveness
      of a teaching program on medication-taking behavior. DESIGN: A descriptive
      correlational study design was used. SAMPLE/SETTING: A total of 26 patients, age
      65 and over, undergoing hemodialysis at an inner city outpatient dialysis clinic
      met sample criteria. METHODS: The instrument included a demographic data form,
      the Iowa Self-Assessment Inventory (ISAI) to measure psychosocial variables, and
      a form to collect data to calculate medication compliance rates. RESULTS: All
      participants were African-American. Mean age was 70. Sample attrition was high.
      Scores were below the norm for most ISAI psychosocial factors, medication
      compliance rates were low, and the teaching intervention did not affect
      compliance rates. CONCLUSION: Medication compliance in this older dialysis
      patient population was problematic, and further research in this area is
      essential.

PMID- 9543909
TI  - Where do young adult renal transplant recipients fit in?
AB  - Young adult renal transplant recipients often have unique concerns and interests.
      To give them an opportunity to share these concerns with peers, a support group
      was established at Boston Children's Hospital. Despite a less than enthusiastic
      beginning, this group is now well attended, meets four times a year, and has
      continued for over 4 years. The group has become a comfortable setting where the
      participants discuss their unique perspectives on schooling, family, and
      relationships.

PMID- 9543910
TI  - Survey of nephrology nurses' interest in graduate education.
AB  - OBJECTIVE: The purpose of the survey was to determine interest in a Master's
      nephrology nursing program among ANNA members residing in North Carolina, South
      Carolina, and Virginia. DESIGN: Needs assessment. SAMPLE/SETTING: 153 ANNA
      members residing in South Carolina, North Carolina, and Virginia. METHOD: Mailed
      survey. RESULTS: Response rate was 27%; 54 (35%) expressed interest in attending
      such a program, with 62 others (41%) interested "depending." Part-time study was
      the most commonly desired program option. Almost half (48%) were not currently
      baccalaureate prepared, a requirement for admission. CONCLUSIONS: Enrollment was
      inadequate to support the program despite numerous marketing efforts, bringing
      into question the adequacy of needs surveys for program planning.

PMID- 9543911
TI  - Maintaining iron balance with total-dose infusion of intravenous iron dextran.
AB  - Recombinant human erythropoietin (rHuEPO) is an important component of anemia
      management in patients with chronic renal failure, however, it can lead to
      functional iron deficiency (FID). Patients with FID are less likely to have an
      optimal response to rHuEPO (Cavill et al., 1997). Intravenous (i.v.) iron dextran
      is often required to replace iron losses, maintain adequate iron stores, and
      correct iron deficiency. The following article provides a rationale for the use
      of IV iron dextran and details one unit's protocol and experience with its use.

PMID- 9543912
TI  - Teaching an illiterate transplant patient.
AB  - RSR is now several years posttransplant. He has a serum creatinine of 2.1 mg/dl
      and his hypertension remains borderline with additional medication. He is seen
      regularly by his local nephrologist and once a year at the transplant center. In
      RSR's case, collaboration with physicians, nurses, and home health helped this
      patient achieve the goal of self-care. Illiteracy was no barrier to achieving
      this goal when assessing the patient's skills, developing a plan that uses those
      skills, and working together as a team to implement the plan.

PMID- 9543913
TI  - Neoral: the new cyclosporine.
AB  - Neoral is an improved formulation of cyclosporine which, through microemulsion
      technology, provides a more consistent rate of absorption and exposure. If
      patients are able to take less Neoral and still maintain the same cyclosporine
      level, there will also be a cost savings involved. A dose reduction of 30% yields
      pharmacoeconomic savings. With a more consistent rate of absorption, the risks of
      nephrotoxicity may be reduced.

PMID- 9543914
TI  - Determining the direction of blood flow.

PMID- 9543915
TI  - Dialysis in the newborn with chronic renal insufficiency: ethical considerations.

PMID- 9543916
TI  - Hemoglobin and hematocrit: an analysis of clinical accuracy. Case study of the
      anemic patient.
AB  - Hemoglobin (Hgb) and hematocrit (Hct) are often used interchangeably to evaluate
      anemia in dialysis patients. Hgb is the preferred method in most European
      countries, while Hct is generally used by clinicians in the United States. This
      article examines the comparative accuracy of these two values, including a same
      patient assessment of laboratory samples. These data illustrate that Hgb is a
      more accurate method of assessing anemia. Using Hgb may help nurses and patients
      by: (a) decreasing variability in laboratory assessment, (b) avoiding ongoing
      errors in anemia measurement, (c) decreasing the nursing time spent on anemia
      management, and (d) increasing the potential for patients remaining in the
      recommended DOQI target Hgb range of 11 g/dL to 12 g/dL.

PMID- 9543917
TI  - Nursing's past, present, and future: looking back in order to move forward.

PMID- 9543918
TI  - Clinical risk modification, quality, and patient safety: interrelationships,
      problems, and future potential.
AB  - Iatrogenic injury, in which patients are unintentionally injured by medical
      treatment, occurs in 4% of hospital admissions and causes considerable human
      suffering, financial losses, and waste of healthcare resources. This article
      discusses why existing quality initiatives have had little impact on iatrogenic
      injury and suggests an approach to clinical risk modification that may enhance
      the safety of medical treatment.

PMID- 9543919
TI  - Measuring patient satisfaction in healthcare organizations: qualitative and
      quantitative approaches.
AB  - Patient perceptions of the quality of services provided are a key factor in
      determining a healthcare organization's competitive advantage and survival. This
      article examines the advantages, disadvantages, and problems associated with nine
      different qualitative and quantitative methods of measuring patient satisfaction
      with service quality and concludes with guidelines for measurement of patient
      satisfaction and implementation of managerial follow-up.

PMID- 9543920
TI  - Technology assessment in healthcare: a review and description of a "best
      practice" technology assessment process.
AB  - BACKGROUND: Technology assessment has become a rapidly growing component of the
      healthcare system. It has assumed a functional role in operational settings and
      is rapidly impacting decisions involving purchasing, coverage, and reimbursement.
      This review is intended to assist the healthcare decision maker in considering
      the application of technology assessment in healthcare, so as to maximize the
      efficiency of future purchasing decisions. METHODS: This "best practice" was
      synthesized after identifying key institutions performing technology assessment
      in healthcare and analyzing their working processes, including literature review,
      consensus panel discussions, and expert opinion. RESULTS: We describe this best
      practice on a reiterative loop that consists of five processes: awareness,
      strategic appropriateness, analysis versus need, acquisition and implementation,
      and reassessment. Typical barriers to adoption of technology assessment are also
      identified and discussed. CONCLUSIONS: This review suggests a common terminology
      for the core processes involved in technology assessment, thereby facilitating a
      more uniform understanding among the different components of the healthcare
      system (i.e., payer, provider, and society) while recognizing their different
      perspectives.

PMID- 9543921
TI  - Disease management: Lovelace Health Systems episodes of care--a case study.
AB  - The evolving paradigm shift in healthcare emphasizes population health status.
      Disease management is gaining popularity as a means of providing cost-effective,
      quality healthcare to an entire population at risk. Outcomes measurements,
      standardized clinical protocols and commitment by physicians and staff are
      crucial to a successful program. This article presents a case study from Lovelace
      Health Systems in Albuquerque, N.M., and identifies key components, cost savings
      and successes of one of its disease management programs.

PMID- 9543922
TI  - Academic health center teaching hospitals in transition: a perspective from the
      field.
AB  - A study of 11 Academic Health Center Teaching Hospitals (ATHs) in 11 states found
      that cost reduction programs, internal reorganizations, reengineering,
      benchmarking, and broadened entrepreneurial activity were prominent among the
      strategic initiatives reported in dealing with an increasingly turbulent
      environment. Although none of the ATHs had experienced negative net margins, we
      conclude that today's competitive healthcare system requires ATHs be reimbursed
      separately for their educational and other societally related costs to assist
      them in competing on a level playing fields.

PMID- 9543924
TI  - Best practices in the best places: benchmarking in the emergency department.

PMID- 9543923
TI  - Attracting RNs to nursing homes: nurses' work experience and perceived importance
      of organization and job attributes.
AB  - Applicant attraction theories stipulate that employment inducements be customized
      to meet the desires and specific characteristics of potential applicants. This
      study examined the relationship between nurses' level of work experience and
      perceived importance of organization and job attributes in attracting them to
      nursing home jobs. Importance ratings of recruitment factors varied significantly
      by nurses' level of work experience. Unique variation was attributed to education
      opportunities, potential for career advancement, compensation issues, benefits,
      and work flexibility.

PMID- 9543925
TI  - A brave New World.

PMID- 9543926
TI  - Transmyocardial laser revascularisation in Edinburgh.
AB  - This paper describes a feasibility study to evaluate the Xenon-Chloride Excimer
      laser in patients requiring myocardial revascularisation. METHODS: Between
      November 1995 and September 1997, 30 patients (aged 48 to 80 years) underwent
      Transmyocardial Laser Revascularisation (TMR), either combined with coronary
      artery bypass grafting (CABG) or as a sole procedure. These patients were
      considered unsuitable for conventional coronary revascularisation on the basis of
      angiographic findings. Evaluation included NYHA status, exercise tolerance test,
      dobutamine stress echocardiography, Thallium myocardial perfusion scan, with
      follow-up scan at 3 months and clinical review at 3, 6, 12 and 18 months.
      Operative technique initially was standardised comprising median sternotomy, full
      cardiopulmonary bypass, moderate systemic hypothermia and induced ventricular
      fibrillation. This was later modified to mini-left anterior thoracotomy, femoral
      cannulation with venous centrifugal assist. RESULTS: Patients undergoing TMR also
      had conventional grafts whenever possible (18/30 (60%), 1 graft 12/30, 2 grafts
      6/30). 14 patients were redo cases, and 12 were unsuitable for further grafts,
      and therefore had TMR as a sole procedure. The number of channels created was
      between 6 and 100 (mean 45.6 +/- 20.7). The majority of the cases had severe
      angina (NYHA classes III or IV) at presentation, with an improvement of at least
      2 points postoperatively (p < 0.001) which was sustained throughout the period of
      follow-up. Objective evidence of improved myocardial perfusion and function
      (dobutamine stress echocardiography and Thallium myocardial perfusion scan) was
      obtained in a few patients. Complications following TMR were uncommon-one patient
      developed complete AV dissociation requiring permanent pacemaker insertion. No
      other specific TMR-related complications were identified. CONCLUSION: Despite
      initial difficulties in recruiting adequate numbers of patients, TMR has proved
      to be a useful adjunct in relieving angina in patients who are either poor
      candidates for surgery or unsuitable for full revascularisation. Modification in
      the technique has allowed a less invasive approach and improved recovery period.

PMID- 9543927
TI  - Record keeping: legally and professionally important?

PMID- 9543928
TI  - Alison Bell Memorial Writer's Award. Research and the practice of scrubbing up in
      theatre.

PMID- 9543929
TI  - Perioperative pain management: a gate control perspective.
AB  - The assessment and management of perioperative pain are critical skills for the
      surgical nurse, hence, the subjective nature of pain should be reflected in their
      approach to pain control. Unfortunately, many studies (Seers 1987, Kuhns et al
      1990, Royal College of Surgeons and Royal College of Anaesthetists 1990, Closs
      1992 and Field 1996) suggest that the nurse's knowledge of perioperative
      management is inadequate. However, as Carr (1997) reported, nurses are not the
      only group of health care professionals who demonstrate a lack of 'expertise' in
      providing analgesic relief. Carr reviewed the survey of 27 medical schools by
      Marcer and Deighton in 1988 which revealed that 4 schools undertook no formal
      teaching on pain control, and the remainder averaged only 3.5 hours during a four
      year course. Clearly, perioperative pain management remains a major problem! We
      have suggested that surgical nurses must have a sound knowledge of the
      neurophysiology associated with this subjective phenomenon (Clancy and McVicar
      1998) since such an understanding is paramount in assisting the decision making
      process which underpins effective individualised perioperative pain management.

PMID- 9543930
TI  - Are you research minded?

PMID- 9543931
TI  - Rearranging the deckchairs on the Titanic.

PMID- 9543933
TI  - Let the bank feed the river.

PMID- 9543934
TI  - Spirituality and practice. Stories, barriers and opportunities. Interview by
      Laurence A. Savett.
AB  - What are "spiritual matters?" Are "spiritual matters" the same as "religious
      matters?" What is spiritual inquiry? Are such questions appropriate for those of
      us in the caring professions, other than clergy, to consider? If we accept that
      role, how far should we go? When should we call for help? Whom should we call? We
      convened a gathering of a hospital chaplain, a social worker, a hospice nurse and
      a physician to discuss many of the dimensions of spirituality and then to apply
      their personal and professional paradigms of care to a discussion of an actual
      case. This article is a record of that conversation. It is actually several
      articles in one, for it deals with their own views of the meaning of
      spirituality, the degree to which their spirituality has impact on their
      practice, what they see as the merit of spiritual matters in the caring
      professions, barriers to collaboration among their professions and to addressing
      these issues with patients, and boundaries beyond which one should not go. One
      way to read this conversation is to include yourself; that is, to reflect on the
      points the participants make and the ways in which you might integrate their
      insights into your personal practice. We hope that you find this task worthwhile
      and that it provokes further thought and discussion. The discussion began with
      participant introductions.

PMID- 9543935
TI  - Spiritual self-care: the healer's journey.

PMID- 9543936
TI  - Hope in healthcare today.

PMID- 9543937
TI  - The patient as focus in differentiating nursing practice.

PMID- 9543938
TI  - Home care's situational crisis.

PMID- 9543939
TI  - Nursing interventions with advanced osteoporosis.
AB  - The patient with advanced osteoporosis presents with multisystem dysfunction, a
      decrease in ability to perform activities of daily living (ADLs), and often both
      acute and chronic pain. These men and women may experience depression and loss of
      self-esteem as well as future disability and increasing physical dependence. In
      the short time and limited visits allowed, the home care nurse can act as
      advocate, teacher, and caregiver in helping these patients to reach the goals of
      maintaining function and improving their quality of life.

PMID- 9543940
TI  - The physical therapist as a member of the home healthcare team: caring for
      patients with replacements.
AB  - The projected life of a total knee and total hip replacement today is
      approximately 15 years. Orthopedic surgeons are therefore very cautious to
      replace joints in patients who are young, believing that if patients receive
      joint replacements in their mild or early 60s, there is a good possibility they
      may outlive the replacement and thereby require a revision. One role of physical
      therapy with the postoperative replacement patient is education of the patient in
      precautions that should be observed and guidelines to be followed for general
      activities. This is very valuable information that should be shared with the
      patient before surgery and reinforced afterward. In the changing healthcare
      environment of the 1990s, home healthcare professionals are being challenged to
      provide effective, skilled care that is the most cost effective and appropriate
      for patients. It is important that all professional home healthcare personnel
      work as a team to accomplish these goals. The PT is an important member of this
      team. After an acute illness or injury, or throughout the course of a chronic
      illness, there are numerous times when home healthcare patients will benefit from
      skilled PT services. Home healthcare nurses are in a unique position to recognize
      the need to work with the patient's physician for referral to other members of
      the healthcare team.

PMID- 9543942
TI  - Home care nursing as a philosophy of care.

PMID- 9543941
TI  - Assessing the high-risk pregnant woman at home.
AB  - Many women with high-risk pregnancies such as pregnancy-induced hypertension and
      preterm labor are being managed in their homes. By using tools designed to detect
      subtle changes in the health status of the woman and her fetus, the home
      healthcare nurse can have a positive impact on the treatment and outcome of the
      pregnancy.

PMID- 9543943
TI  - Pharmacologic pain. Management for cancer patients at home.
AB  - Pain management is one of the most important responsibilities of the home care
      nurse serving cancer patients. Patients and caregivers often fear uncontrolled
      pain, and need frequent reassurance that effective pain control can be achieved.
      This article discusses the etiology and types of cancer pain, pain assessment,
      pharmacologic pain management interventions, and evaluation of pain management
      for home care patients.

PMID- 9543944
TI  - Beyond venipuncture as the qualifying service for Medicare: seeing the forest for
      the trees.

PMID- 9543946
TI  - A message from a client.

PMID- 9543945
TI  - Sexual activity and knowledge of safe sex reported by HIV-infected persons
      receiving home care.
AB  - Sexual activity and knowledge of safe sex were assessed for 57 human
      immunodeficiency virus (HIV)-infected persons on admission to home care. More
      than one third of the individuals providing information were sexually active; 72%
      of the sexually active persons reported that they practiced safe sex. Definitions
      of safe sex were inconsistent, particularly regarding safety of oral sex. Needs
      for counseling on safe sex of HIV-infected persons receiving home care practices
      were clearly evident.

PMID- 9543947
TI  - Home care fraud & abuse: dishonest documentation.

PMID- 9543948
TI  - The coffee connection: the benefits of memory.

PMID- 9543949
TI  - The American Academy of Pediatrics recommendations on breastfeeding and the use
      of human milk.

PMID- 9543951
TI  - HIV transmission via breastfeeding: reflection on the issues.

PMID- 9543950
TI  - Fortified human milk: nature's way to feed premature infants.

PMID- 9543952
TI  - Rethinking latch-on problems.

PMID- 9543953
TI  - Breastfeeding as the norm.

PMID- 9543954
TI  - WIC-based interventions to promote breastfeeding among African-American Women in
      Baltimore: effects on breastfeeding initiation and continuation.
AB  - We evaluated the single and combined effects of introducing a motivational video
      and peer counseling into four matched WIC clinics on breastfeeding initiation and
      continuation at 7-10 days among African-American WIC participants. Of the 242
      women with complete data, 48% initiated breastfeeding, but only 31% were still
      breastfeeding at 7-10 days. Initiation was associated with cesarean delivery,
      infant feeding instruction, no artificial milk discharge pack, attending the peer
      counselor only-intervention site, and intention to breastfeed. Continuation was
      influenced by infant feeding instruction, no artificial milk discharge pack, and
      intention to breastfeed. Overall, trends toward a positive impact of the
      breastfeeding promotion activities were evident but weak, and largely gone by 7
      10 days postpartum.

PMID- 9543955
TI  - The anticarcinogenic conjugated fatty acid, 9c, 11t-18:2, in human milk:
      confirmation of its presence.
AB  - The concentration of the anticarcinogenic fatty acid, 9c, 11t-18:2, in human milk
      was determined by gas-liquid chromatography (GLC). The mean concentration of 20
      samples from 5 women taken at 1, 7, 14, and 21 days was: 0.18% +/- 0.02; range,
      0.14-0.28%. Identity was confirmed by GLC-mass spectrometry (MS). Conjugated
      isomers other than 9c, 11t-18:2 were not detected. The amounts were not changed
      by supplementation of the maternal diet with fish oil beginning on day 1 after
      the milk sample was taken.

PMID- 9543956
TI  - Breastfeeding of very low birth weight infants.
AB  - This research examines the rate of breastfeeding among mothers of very low birth
      weight infants (VLBW, < 1500 grams), and the correlates of breast milk pumping
      and transition to nursing at the breast. Eighty-two mothers and their 69
      singleton and 21 twin VLBW infants admitted to the Neonatal Intensive Care Unit
      (January 1-June 30, 1995) of an urban tertiary care hospital. Maternal
      demographic, infant birth, and neonatal data were compared according to breast or
      bottle feeding, and a telephone interview was administered retrospectively to
      mothers pumping breast milk at the time of the infant's discharge home. Of 39
      mothers who chose to pump breast milk, 19 were still pumping at the time of the
      infant's discharge home. Only 8 made a successful transition to nursing at the
      breast. Mothers who continued pumping tended to be white, married, and older, and
      their infants had fewer neonatal complications. The rates of prolonged breast
      milk pumping and of nursing are very low. Specific interventions and better
      support might improve the success rates.

PMID- 9543958
TI  - The role of social support in breastfeeding promotion: a literature review.
AB  - The current worldwide decline in the initiation and duration of breastfeeding has
      increased the need for effective breastfeeding promotion. Promotion policies and
      programs need to be sensitive to those factors that may help or hinder a mother
      in her efforts to breastfeed. Such factors include sociodemographic
      characteristics, maternal employment, and social support. Social support that
      increases breastfeeding includes emotional, tangible, and educational components
      from both informal social network members (male partner, mother, family/friends)
      and professional network members (health care professionals, lactation
      consultants). Conversely, negative social support may decrease breastfeeding.

PMID- 9543957
TI  - Prenatal lactation advice and intention to breastfeed: selected maternal
      characteristics.
AB  - This study uses data from the NICHD/MMIHS to examine the relationship among
      maternal characteristics and (a) whether mothers were asked by their prenatal
      providers to consider breastfeeding and (b) mothers' prenatal plans on how to
      feed their infants. Only 37% of the study population reported that their
      providers advised them to consider breastfeeding. Proportions of women who
      received prenatal advice to breastfeed and who intended to breastfeed were higher
      among married, Caucasian non-Hispanic, primiparous mothers, and women who were
      not enrolled in WIC. Women who received advice to breastfeed had significantly
      higher rates of planning to breastfeed (61.1%) than women who did not receive
      this advice (34.7%; p < 0.005). Efforts to meet the DHHS Healthy People 2000
      objective for 75% of women to breastfeed in the early postpartum period will
      require a concentrated effort by prenatal providers to help women overcome their
      resistance to breastfeeding by offering support and encouragement.

PMID- 9543959
TI  - Breastfeeding a baby with a cleft palate: a case report.
AB  - A case report is presented on the experience of breastfeeding a baby with a cleft
      palate. The importance of breastfeeding for the baby and the mother is discussed
      as well as the importance of support from health care professionals. Problems are
      described relating to (a) the long term maintenance of lactation by exclusive
      breast pumping; and (b) the lack of information available on feeding techniques
      and devices helpful in breastfeeding prior to and following palate repair.
      Practical suggestions are proposed for expressing and feeding expressed milk to a
      baby with a cleft palate.

PMID- 9543960
TI  - A breastfeeding teaching tool using a sandwich analogy for latch-on.
AB  - Effective latch-on is central to comfortable, efficient breastfeeding. Since
      breastfeeding involves taking a large mouthful of an even larger object, a latch
      on teaching model based on bottle-feeding or on suction alone may be
      inappropriate. A model based on the way in which an adult approaches a large
      sandwich, using a water balloon to demonstrate, can help a mother and baby
      achieve an effective latch-on for breastfeeding.

PMID- 9543961
TI  - Statistical report of the 1997 IBLCE Examination.

PMID- 9543962
TI  - Sedatives and hypnotics in lactation.

PMID- 9543963
TI  - How to order banked donor milk in the United States: what the health care
      provider needs to know.

PMID- 9543964
TI  - Effects of preoperative ambulatory gynecological education: clinical outcomes and
      patient satisfaction.
AB  - Because of the limited access to health care providers in ambulatory care,
      individual patients must assume presurgical and postsurgical responsibility for
      their own well-being. The purpose of this study was to identify optimal methods
      of preparing patients for surgery. The clinical outcomes, length of stay in PACU,
      and satisfaction of two groups of patients were compared using an experimental
      design. Thirty patients who were scheduled for laparoscopic tubal ligation were
      randomly assigned to either the experimental (structured) or control
      (unstructured) education program. Clinical data about return to baseline vital
      signs, use of analgesics, experiences of nausea and vomiting, and length of stay
      in PACU were assessed via retrospective chart review. Patient satisfaction with
      the instruction program was measured by a telephone interview using the Patient
      Satisfaction Index. Results of t-tests, repeated measures (ANOVA), and sign tests
      identified no significant differences concerning clinical outcomes except for
      analgesics requested and received. Time between Phase I and Phase II and
      discharge was not statistically significant. Future research is needed on major
      ambulatory surgical procedures combined with an alternate method to assess
      attitudinal data.

PMID- 9543965
TI  - Factors influencing successful discharge after outpatient laparoscopic
      cholecystectomy.
AB  - Advanced laparoscopic and laser technologies have revolutionized the treatment of
      gallbladder disease. A new treatment, laparoscopic cholecystectomy, allows direct
      visualization of the abdominal cavity by means of a laparoscope and the removal
      of the gallbladder with only four small 0.5-inch incisions. For the majority of
      laparoscopic cholecystectomy patients, this service is provided in an ambulatory
      surgery or free-standing outpatient surgery center. Ambulatory surgery patients
      must meet established criteria before being discharged, but not all patients are
      successful in meeting discharge criteria. Many must be admitted overnight for
      further observation and treatment. Problems delaying discharge at one facility
      related to pain control, inability to ambulate, or uncontrolled nausea. This
      inability of patients to be discharged impacted on unit staffing, hospital
      productivity and cost, and patient satisfaction. This article discusses the
      factors that influenced the discharge outcome of patients undergoing elective
      laparoscopic cholecystectomy surgery at an ambulatory surgery center in an urban
      community hospital. Contributing factors included time of surgical procedure,
      comorbidity, premedication for pain (preemptive analgesia), and incisional local
      anesthesia. This information is important to providers caring for this patient
      population. Careful screening processes and development of treatment protocols
      related to the contributing factors will enhance the ability to safely discharge
      laparoscopic cholecystectomy patients.

PMID- 9543966
TI  - Perianesthesia care of adult and pediatric strabismus surgery patients.
AB  - Strabismus procedures on children and adults are frequently performed in an
      outpatient setting. Perianesthesia care of patients having strabismus procedures
      may be optimized by recognizing the characteristics of strabismus patients, the
      frequently associated diagnoses that may affect perioperative care, and the
      specific surgical techniques used to treat strabismus. Complications including
      postoperative nausea, pain, prolonged PACU stay, and unplanned postoperative
      admissions can be minimized and treatment facilitated by preparing patients with
      preoperative instructions, careful choice of anesthetic agents and postoperative
      medications, and appropriate perioperative care. This report will provide a brief
      review of surgical strabismus, including current techniques, and present
      guidelines for perioperative care of pediatric and adult strabismus patients.

PMID- 9543967
TI  - Computer and information technology: hardware.
AB  - Computers open the door to an ever-expanding arena of knowledge and technology.
      Most nurses practicing in perianesthesia setting were educated before the
      computer era, and many fear computers and the associated technology. Frequently,
      the greatest difficulty is finding the resources and knowing what questions to
      ask. The following is the first in a series of articles on computers and
      information technology. This article discusses computer hardware to get the
      novice started or the experienced user upgraded to access new technologies and
      the Internet. Future articles will discuss start up and usual software
      applications, getting up to speed on the information superhighway, and other
      technologies that will broaden our knowledge and expand our personal and
      professional world.

PMID- 9543968
TI  - Differentiation of atrioventricular blocks.
AB  - In closing, it has been the purpose of this article to present and elaborate on
      the types of AV blocks, their clinical significance and causes, nursing
      interventions, and treatments associated with their management. The nurse that
      has knowledge of these heart blocks will be well equipped and prepared to
      promptly treat a patient suffering from AV block.

PMID- 9543969
TI  - Science and theory.
AB  - This manuscript presents some of the basic concepts of science and scientific
      reasoning. Whether you are reading research or planning to do a Master's thesis,
      understanding these concepts will be important. How theories differ from beliefs
      and their ultimate practicality are discussed.

PMID- 9543971
TI  - Forget authority--go for power.
AB  - Real power comes from the ability to influence other people. The organization is
      constantly changing, and when it gives a manager authority, it does not confer
      power with it. With authority comes responsibility and accountability. What
      managers need is power. Power comes from understanding values, and is the key to
      bridging the gap between authority and accountability.

PMID- 9543970
TI  - Postextubation laryngeal edema: a review with consideration for home discharge.
AB  - Respiratory complications occurring in the immediate postoperative period are
      well known to the seasoned postanesthesia care unit nurse. The most common
      adverse respiratory events originating in this setting are airway obstruction,
      hypoventilation, hypoxemia, and pulmonary aspiration of gastric contents. The
      focus of this article details airway compromise secondary to edema of the larynx
      and adjacent structures as a consequence of translaryngeal intubation.
      Postextubation laryngeal edema is a relatively rare problem; however, severe
      episodes may have life-threatening ramifications. A review of pertinent airway
      anatomy and airflow dynamics as they relate to this compromised airway condition
      is presented. Risk factors for the development of postextubation laryngeal edema
      plus contemporary patient treatment strategies will be reinforced. Patient
      management issues are addressed, with emphasis placed on the ambulatory patient
      in which discharge to a remote location is anticipated.

PMID- 9543972
TI  - Treat them tenderly.

PMID- 9543973
TI  - The challenge of effective professional practice.

PMID- 9543974
TI  - A comparison of dressings in the management of surgical abdominal wounds.
AB  - This prospective randomised trial compared the performance of three dressing
      protocols in the management of 36 dehisced surgical abdominal wounds: a standard
      alginate; a gauze moistened with sodium hypochlorite (0.05%); and a combine
      dressing pad. Outcomes assessed were: healing time (cm2 per day and cm3 per day),
      patient comfort (pain and satisfaction) and cost. There were no statistically
      significant differences in healing rates between the three groups but there was a
      trend for the combine dressing pad protocol to produce a greater reduction in
      wound area. The combine dressing pad protocol performed well when compared with
      the calcium alginate in terms of healing time, patient comfort and cost. Maximum
      pain was significantly greater (p = 0.011) and satisfaction significantly lower
      among patients who received the sodium hypochlorite protocol. Costs during the in
      patient phase were also substantially higher for the sodium hypochlorite
      protocol. Trial results support the view that sodium hypochlorite dressing
      protocols for surgical wounds should be abandoned.

PMID- 9543975
TI  - A comparison of two amorphous hydrogels in the debridement of pressure sores.
AB  - This study compared the efficacy of two hydrogel dressings in the debridement of
      necrotic pressure sores. This randomised, controlled, assessor-blind, clinical
      trial involved 50 patients whose wounds were assessed weekly using computerised
      wound analysis for four weeks or until debrided. Debridement was identified when
      there was 80% red granulation tissue present and no sign of necrosis. There were
      no statistically significant differences in comfort, wound odour, surrounding
      skin condition or time to debridement between the two groups.

PMID- 9543976
TI  - An evaluation of hyper-oxygenated fatty acid esters in pressure sore management.
AB  - The aim of this study was to use transcutaneous oxygen pressure (tcpO2)
      measurements to evaluate the efficacy of a solution containing hyper-oxygenated
      fatty acid esters in the prevention of pressure sores in 28 patients at high risk
      of developing sores. Statistical analysis indicates a significant difference
      between tcpO2 values during pressure exertion before and after application of the
      product (p = 0.014). Oxygen pressure values decreased significantly when the
      patient applied pressure to the sacral area before the test product was applied
      whereas no difference in oxygen pressure values was noted after application of
      the test product.

PMID- 9543977
TI  - Hospital-acquired pressure sores in surgical patients.
AB  - This study is based on a retrospective analysis of case notes of 314 elective and
      emergency patients who underwent major surgical procedures between November 1995
      and March 1996. The research is part of a larger project on pressure sores in
      surgical patients. The effects of patient characteristics and the organisational
      processes of care on the development of hospital-acquired pressure sores were
      examined. Factors identified can be used as parameters in the assessment of
      pressure sore risk in surgical patients. This report presents the preliminary
      results of the univariate statistical analysis.

PMID- 9543978
TI  - Wound-healing problems associated with cancers.

PMID- 9543979
TI  - Minimising risk factors in pressure sore care.

PMID- 9543980
TI  - Pressure sore risk assessment.

PMID- 9543981
TI  - Community leg ulcer clinics and the effectiveness of care.

PMID- 9543982
TI  - Healing in the nasal mucosa.

PMID- 9543983
TI  - The pathophysiology and treatment of diabetic foot disease.

PMID- 9543985
TI  - [The concept and practice of empowerment related to health promotion].

PMID- 9543984
TI  - [Health promotion in health education].

PMID- 9543986
TI  - [Self control and self care].

PMID- 9543987
TI  - [Modeling theory and its future in health education].

PMID- 9543988
TI  - [Diabetes education and self efficacy].

PMID- 9543989
TI  - [Nursing care of children requiring home parental nutrition and their families:
      descriptive study of 7 children with gastrointestinal disorders].

PMID- 9543991
TI  - [Development of an observational method of sleep state].

PMID- 9543990
TI  - [Relationship between the experience of steroids side effects and noncompliance
      with oral steroids treatment in collagen disease patients].
AB  - PURPOSE: To analyze the relationship between the experience of side effect and
      the compliance with oral steroids drug treatment of the patients in Collagen
      Disease Clinic. METHODS: A questionnaire survey through interview was conducted
      on 165 outpatients with various collagen disease at Saga Medical School Hospital.
      RESULTS: 94 patients (57%) had a history of noncompliance to the steroids drug.
      49 patients (52.1%) adventitiously had forgotten to take the steroids as ordered
      and 45 patients (47.9%) intentionally had regulated their steroids dose or had
      discontinued the steroids drug treatment. Over 80% of the patients had
      experienced side effects of the steroids. The patients who experienced one or
      more of the following side effects, osteoporosis, bone fractures, menstrual
      disorders, moon face, central obesity, alopecia, acnelike eruption, manic
      depressive state, and insomnia, intentionally regulated, or discontinued the
      steroids therapy. In addition, the patients who were not made cognizance about
      side effects of the steroids by their physicians and nurse tended to
      noncompliance group. CONCLUSION: To increase the compliance rate with oral
      steroids drug treatment, we must make conscious efforts to inform the patients on
      the condition of their medical states, the efficacy of the prescribed drugs, and
      the side effects and risk concerning discontinuation of the steroids. It is Also
      necessary to establish "Drug information and counseling day" in outpatient
      Department.

PMID- 9543992
TI  - [Quality of life of children and adolescents with cancer: telling diagnosis,
      support systems, length of hospitalization, and home care].

PMID- 9543994
TI  - [Survey and research (12). Steps in the survey process: testing reliability of
      scales].

PMID- 9543993
TI  - [Survey of studies on the role of play in child nursing].
AB  - In this survey, 103 papers submitted to several nursing societies and published
      in leading nursing journals are outlined and analyzed in terms of motives for
      studies, kinds of play enjoyed by the subjects and effects of play on members of
      ward staff, child patients and their family members. The articles are listed in
      chronological order so that the changes and trends in the studies in this field
      will be shown. Studies on play started and developed in the clinical field for
      better ward management and more effective treatment. However, effects of play on
      development of child patients gradually became the focus of the studies. In terms
      of the subjects' level of health, it used to be limited to chronically
      hospitalized patients who were not behaviorally limited. The scope of the
      subjects has widened to include "every health level". It's now purported that
      every patient regardless of his/her health level should enjoy the benefits of
      play. Regarding kinds of play, indoor plays were initially predominant, but
      subsequently outdoor activities became more popular with the playing repertoire
      increasing. Infantile stage has been and still is most frequently discussed in
      the field, while other developmental stages are now attracting more attention
      than before.

PMID- 9543996
TI  - Juggling work and the family.

PMID- 9543997
TI  - Liability arising out of professional disciplinary law.

PMID- 9543998
TI  - Dealing with chronic illness.

PMID- 9543999
TI  - ANF Biennial Conference.

PMID- 9544000
TI  - Inreach team's a winner.

PMID- 9544001
TI  - Nurses' attitudes to voluntary euthanasia.

PMID- 9544003
TI  - President's report.

PMID- 9544004
TI  - Jo Leavy. Interview by Kimberly O'Sullivan.

PMID- 9544005
TI  - Taking time for ourselves.

PMID- 9544006
TI  - Breaking the boundaries: collaborating to develop a model ventilator training
      program.
AB  - Changes in the health care system have created new opportunities for acute care
      nurses to establish collaborative relationships with their rehabilitation
      partners. When a rehabilitation facility decided to establish a ventilator
      weaning rehabilitation program, an acute care facility joined forces with the
      institution to develop an educational plan for the nursing staff. The development
      and implementation of the educational program as well as the collaborative
      relationship established between the two facilities are highlighted in this
      continuing education article.

PMID- 9544007
TI  - The integration of a tuberculosis control plan into a standard of care for
      tuberculosis.
AB  - Tuberculosis is a significant public health problem. Health care agencies and
      hospitals are mandated to have in place protocols to manage patients with
      suspected or confirmed cases and to implement infection control measures to
      prevent the spread of the disease. A facility with a high percentage of infected
      patients developed and integrated a standard of care to improve the management
      and outcomes of infected patients.

PMID- 9544008
TI  - Implementing a residency program for the acute care nurse practitioner.
AB  - A clinical residency program for acute care nurse practitioners (ACNPs) was
      developed to facilitate the strengthening of practice competencies and role
      performance. Strengthening collaboration between physicians and ACNPs and
      supporting the growth of ACNPs through supportive and individualized learning
      opportunities were key components to a highly successful initiative.

PMID- 9544009
TI  - Nurses' perceptions of why medication administration errors occur.
AB  - Nurses play a key role in medication administration in hospital settings. Five
      categories of reasons for medication errors were identified in a survey of 1,384
      nurses. These categories include physician, systems, pharmacy, individual, and
      knowledge-related factors. In this article, issues surrounding the occurrence and
      prevention of medication errors are discussed.

PMID- 9544010
TI  - Describing pain management documentation.
AB  - Managing postsurgical pain continues to be one of the nation's top clinical care
      priorities and concerns. Despite widely publicized national care guidelines,
      effective pain management for all patients is not a reality. This study explored
      how nurses in a community hospital documented the process of pain management for
      a group of postsurgical patients. The results have implications for all adult
      health nurses.

PMID- 9544011
TI  - In search of a 'magic' pill to treat obesity: the rise and fall of 'Fen-Phen'.

PMID- 9544012
TI  - A road map for navigating end-of-life care.
AB  - As nurses begin to develop the sensitivities and skills necessary to preserve the
      integrity of clinical care and professional life, they must recognize the
      legitimacy of their perspectives and the value and consequences they have for the
      well-being of patient and family care. Nurses have much to contribute to the
      development of ethical practice environments for patients, families,
      multidisciplinary team members, and themselves. The frenzied, and at times
      anesthetized, culture of clinical settings can mitigate against the kind of
      deliberate reflection that is necessary if nurses are to act with ethical
      integrity. Knowing the rules of the road for end-of-life care and being attentive
      to common warning signs and addressing them proactively, enables nurses to
      provide patients and families with the highest quality care at the end of life.

PMID- 9544013
TI  - Transforming the workplace.

PMID- 9544014
TI  - An update on nursing involvement in hospital governance: 1990-1996.
AB  - The purpose of this study was to examine the nature and extent of nursing
      involvement in hospital governance in 1994; compare the 1994 level of involvement
      to 1990 levels; compare 1990 projections for 1995 to the actual state in 1994;
      and examine CNEs' projections of the nature and extent of involvement in 1996.
      The database compiled in the study and the author's earlier work (Havens, 1990,
      1992) will assist in efforts to monitor nursing's status in hospital policy
      making as monumental structural changes take place in health care organizations.

PMID- 9544015
TI  - Managing change in health care redesign: a model to assist staff in promoting
      healthy change.

PMID- 9544016
TI  - Delegation skills and nurse job satisfaction.
AB  - In this study, the mean age was 41 and these nurses had been out of school for
      approximately 13 years. Over half of these RNs had never been taught delegation
      skills in nursing school. Of those who were exposed to the concept of delegation,
      their skills were not adequate to meet the patient care demands in the
      restructured health care system. During these challenging periods in health care,
      it is imperative that nursing service administrators provide RNs with the
      continuing education necessary to develop delegation strategies to adapt to their
      evolving professional roles. Continuing education classes on delegation skills
      are requisite for RNs practicing in a competitive managed care environment. As we
      approach the year 2000, the economic climate will dictate that RNs be skilled not
      only as clinicians, but also as leaders of the health care team. The findings of
      this study support that delegation decision-making skills enhance job
      satisfaction in the areas of decision making and promotional opportunity.
      Delegation knowledge is crucial to the successful direction of the health care
      team in the managed care environment.

PMID- 9544017
TI  - Facilitating instrument evaluation.

PMID- 9544018
TI  - Information technology: strategies for success.

PMID- 9544019
TI  - Awake and talking: ambulatory surgery and conscious sedation.

PMID- 9544021
TI  - Are you aware?

PMID- 9544020
TI  - Turnaround hospitals...

PMID- 9544022
TI  - About being a nurse...

PMID- 9544023
TI  - Does JCAHO require one nurse executive?
AB  - Rumors have been flying that the Joint Commission is going to eliminate the
      requirement for a single nurse executive as required by standard NR. 1 in the
      Comprehensive Accreditation Manual for Hospitals (CAMH). This column clarifies
      the JCAHO's intent in this regard.

PMID- 9544024
TI  - Subacute care: creating alternatives. Reengineering: the key to survival and
      growth under PPS.
AB  - Many postacute care providers are concerned about the effects of the prospective
      payment system on skilled nursing facilities. To retain their contractual
      arrangements, physical, occupational and speech therapists are trying to develop
      services within the financial constraints the PPS imposed. Management and staff
      of SNFs also are struggling with the Resource Utilization Groups III and the
      Minimum Data Set that will be the basis for the predetermined, per diem, all
      inclusive fixed rate to be paid. The most logical approach to dealing with this
      crisis is to reengineer all of the SNFs' processes.

PMID- 9544025
TI  - Risk adjustment for health status.
AB  - A managed care plan's capitation payments should include an adjustment for its
      members' health status. Demographic and diagnostic information can be used to
      make the adjustment, which would help to minimize a health plan's potential
      financial liabilities. Without the adjustment, health plans have an incentive not
      to enroll persons with the heaviest care needs.

PMID- 9544026
TI  - A new millennium for health care IT: the year 2000 conversion.
AB  - The new millennium. It means many things for many people, from astrologers to
      information technology (IT) professionals. But the latter, especially those in
      health care, have good reason to be concerned. Because for the majority of
      computer systems, January 1,2000, marks both the beginning of a new decade and
      total system chaos.

PMID- 9544027
TI  - Liability for falls.
AB  - Reengineering of roles, inexperienced personnel and poor communications among
      departments has led to an increase in patient falls--a major source of liability.
      While health care facilities are not liable for all falls, they are expected to
      take precautions based on patients' deficits.

PMID- 9544028
TI  - Competencies drive decision making.
AB  - Staff nurses, using the Nursing Interventions Classification, selected the core
      competencies, performance criteria and interventions relevant to their practice.
      A performance-based approach highlights performance outcomes and previous
      experience. A preceptor and self-directed learning activities help apply the
      knowledge in the work setting.

PMID- 9544029
TI  - A nursing fellowship--building leadership skills.
AB  - A postgraduate nursing fellowship helps future nursing leaders deal with constant
      change, focus on learning and development, think systemically and mobilize
      resources through team building and goal directedness. An administrative
      fellowship program helps to develop future leaders, with the skills necessary to
      assume key positions in health care. Core competencies--leadership criteria,
      roles of the fellow and preceptor, skills of the fellow and preceptor and
      fellowship projects--are described.

PMID- 9544030
TI  - The leader meter--a feedback survey.
AB  - A survey rates leadership behavior at all levels. The confidential feedback
      survey accomplishes three things: (1) it gives valuable feedback about leadership
      skills; (2) it gives employees a voice or a chance to be heard; and (3) it
      encourages teambuilding.

PMID- 9544031
TI  - Continuing care beyond the hospital walls and onto the streets.
AB  - Trauma center nurses joined forces with their city's leaders and organizations to
      address juvenile violence and crime. Metropolitan Partners Against Crime's
      primary initiatives focus on overcoming race, class and gender variances and
      establishing community awareness programs.

PMID- 9544032
TI  - A patient resource program--strengthening primary nursing.
AB  - A patient resource program addresses fragmentation of care, duplication and
      blurred accountability. This centralized referral service uses experts such as
      clinical nurse specialists, enterostomal therapists and pain management nurses to
      improve the primary nursing care model.

PMID- 9544033
TI  - Managing nurse managers--what is the secret?
AB  - What can managers do to ensure a nurse manager's competency and effectiveness in
      today's dynamic health care environment? Strategies on how to lead nurse managers
      and, in turn, help build a strong health care environment through effective
      nursing management are given.

PMID- 9544034
TI  - Nursing council ... coordination within decentralization.
AB  - A nursing council modeled after the traditional five nursing roles--manager,
      educator, practitioner, evaluator and researcher--improves patient outcomes and
      enhances nurse work satisfaction. The council provides a participative forum to
      address nursing and patient-care issues within a decentralized matrix
      organization.

PMID- 9544035
TI  - Peer interviewing: sharing the selection process.

PMID- 9544036
TI  - Initiating action through understanding.

PMID- 9544037
TI  - About preparing for managed care.

PMID- 9544038
TI  - The time of their lives.

PMID- 9544039
TI  - Debate of the age.

PMID- 9544041
TI  - He's doing it my way.

PMID- 9544040
TI  - Cradle to bus pass.

PMID- 9544042
TI  - A healthy outlook?

PMID- 9544043
TI  - A healthy outlook?. Interview by Charlotte Alderman.

PMID- 9544044
TI  - Patients first.

PMID- 9544045
TI  - Organising the workforce: annual hours in nursing.

PMID- 9544046
TI  - Managing pressure sores.

PMID- 9544048
TI  - The student's role in child nursing.

PMID- 9544047
TI  - Learn about plans for the health service of tomorrow.

PMID- 9544049
TI  - Forum bridges the divide.

PMID- 9544051
TI  - Healthy practice is vital for teachers.

PMID- 9544050
TI  - Clinical placements--are students treated properly?

PMID- 9544052
TI  - Practical procedures for nurses. 9.2. Mouth care--2.

PMID- 9544053
TI  - Nutrition in practice. 10. Nutrition and the elderly.

PMID- 9544054
TI  - It's purely professional.

PMID- 9544055
TI  - Calming measures.

PMID- 9544056
TI  - Losing contact with ground control.

PMID- 9544057
TI  - Legislation in the area of HIV infection.

PMID- 9544059
TI  - Nursing management.

PMID- 9544058
TI  - Mental health services.

PMID- 9544060
TI  - Not a plain sailing.

PMID- 9544061
TI  - Me and my doll.

PMID- 9544062
TI  - On duty off shore.

PMID- 9544063
TI  - Elderly care--waiting for a health return. Interview by Janet Snell.

PMID- 9544064
TI  - Mental health--out of the darkness.

PMID- 9544065
TI  - Face to face. Interview by Craig Kenny.

PMID- 9544066
TI  - Forensic nursing.

PMID- 9544067
TI  - Sexually transmitted diseases. Gonorrhoea: symptoms and treatment.
AB  - This article continues our series looking at common sexually transmitted
      infections. It focuses on gonorrhoea, its symptoms and treatment. The nursing
      management and patient's experience are discussed in a case study.

PMID- 9544068
TI  - Developing a reflective standard of care.
AB  - Developing and monitoring effective practice is essential in health care
      organisations. Reflective practice offers practitioners and organisations a means
      to understand and learn through experience in complex care situations and develop
      expertise. This paper describes standard-setting in a hospice to construct a
      standard for managing patients who exhibit aggressive behaviour as part of their
      terminal illness.

PMID- 9544069
TI  - The care programme approach: a patient perspective.
AB  - This study explores the attitudes and experiences of one group of patients on the
      care programme approach living in an outer London borough. There was evidence to
      suggest that patients were unfamiliar with their treatment programmes and lacked
      knowledge regarding their care. Further research into patient attitudes to the
      CPA would be beneficial, since it was not possible to make precise conclusions
      based on this study.

PMID- 9544071
TI  - Feed the patient, fool the pancreas.

PMID- 9544070
TI  - Skills for preventing aggression.
AB  - This case study shows how the assessment and action taken helped a person with
      severe learning disabilities to adjust to life outside a hospital secure unit.

PMID- 9544072
TI  - Know how nutritional assessment.

PMID- 9544073
TI  - Gut instinct.

PMID- 9544074
TI  - Feeding a habit.

PMID- 9544075
TI  - Latex sensitisation--what causes it and what can be done to minimise the risks:
      Part 2.

PMID- 9544076
TI  - Advanced practice and consent.

PMID- 9544077
TI  - Preventing skin cancer.

PMID- 9544078
TI  - Clinical supervision for all.

PMID- 9544079
TI  - Clinical supervision for specialist nurses.
AB  - The UKCC has stated that every practitioner should have access to clinical
      supervision. There is little literature on the supervision needs of specialist
      nurses. Choosing the appropriate model of supervision and establishing formal
      ground rules was essential to the success of the project.

PMID- 9544080
TI  - Audit of nutritional practice and knowledge.
AB  - An audit of nutritional practice was carried out in one NHS trust. Findings
      demonstrated areas for improvement, particularly in the documentation of
      nutritional status and in criteria for referral for specialist help. An
      assessment sheet and a nursing care plan were developed to assess patients' risk
      of being malnourished and to provide a recognised place for recording nutrition
      related information.

PMID- 9544081
TI  - Peripherally inserted central catheters.
AB  - Peripherally inserted central catheters (PICCs) can meet the needs of patients
      requiring short- to intermediate-term intravenous therapy in a variety of
      settings. PICCs minimise insertion and catheter-related complications when
      compared to other central venous access devices (CVADs). PICCs have been
      introduced in the UK mainly through innovative advanced nursing practice.

PMID- 9544083
TI  - Post-herpetic neuralgia.

PMID- 9544082
TI  - Skin cancer.

PMID- 9544084
TI  - Nurse prescribing in diabetes.
AB  - The adjustment of diabetes medication is vital for the prevention of
      complications. Insulin dose adjustment by diabetes specialist nurses is common
      practice but its legality is questionable. Two surveys were undertaken to
      identify common practice. The results were used to establish the basis for an
      effective multiprofessional protocol for nurse administration of diabetes
      medication.

PMID- 9544085
TI  - Family attitudes to bed-wetting and their influence on treatment.
AB  - Bed-wetting can have far-reaching social consequences for the whole family. Seven
      types of attitude towards bed-wetting have been identified that can be strongly
      predictive of behaviour, including the readiness to engage in and persist with
      treatment. Understanding the family's perspective enables a dialogue to be
      engaged in which takes account of the reality of the family's circumstances.

PMID- 9544086
TI  - Consent and children.
AB  - While children aged 16 and 17 years can consent to any surgical or medical
      procedure, for those under 16, adults with parental responsibility may give
      consent on their behalf. If parents and child disagree, however, the doctor
      usually has a choice as to whose wishes he or she should follow.

PMID- 9544087
TI  - Changing practice.

PMID- 9544088
TI  - Ethics in action.

PMID- 9544089
TI  - A CHF program that focuses on best practices and benchmarks.

PMID- 9544090
TI  - New hypertension guidelines. Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure.

PMID- 9544091
TI  - When your patient is on an insulin pump.

PMID- 9544092
TI  - What's wrong with this patient?

PMID- 9544093
TI  - Another way to open an airway.

PMID- 9544094
TI  - As America ages. Assessing the older patient.

PMID- 9544095
TI  - Getting a better read on thermometry.

PMID- 9544096
TI  - The legal implications of genetic testing.

PMID- 9544097
TI  - Making HIV therapy more manageable.

PMID- 9544098
TI  - Keep your boss happy.

PMID- 9544099
TI  - [Straight to a criminal case. Interview by Claus Leick].

PMID- 9544100
TI  - [Management should take a stand. Interview by Claus Leick].

PMID- 9544101
TI  - [Experiencing the situation differently. Interview by Claus Leick].

PMID- 9544102
TI  - [There is a lack of discussion and frankness. Interview by Claus Leick].

PMID- 9544103
TI  - [Regulations on the way about force against demented patients].

PMID- 9544104
TI  - [Regulations ensure safety. Interview by Kirsten Bjornsson].

PMID- 9544105
TI  - [Provide demented patients with a companion in the system. Interview by Kirsten
      Bjornsson].

PMID- 9544106
TI  - [Difficult with ban against code lockup. Interview by Kirsten Bjornsson].

PMID- 9544107
TI  - [Overlook hidden medication].

PMID- 9544108
TI  - [Farewell to telephone lines and TV lounges].

PMID- 9544109
TI  - [Prevention--health gulf between rich and poor must be discarded].

PMID- 9544110
TI  - [Observations on progress of care].

PMID- 9544111
TI  - [Executive Board--members question services].

PMID- 9544112
TI  - [Executive Board--close contact with employers].

PMID- 9544113
TI  - [From the mail box].

PMID- 9544114
TI  - [Nursing--failure can be prevented].

PMID- 9544115
TI  - [Education--research: the young ones lack real knowledge about nursing].

PMID- 9544116
TI  - [Education--campaign: new image of the profession].

PMID- 9544117
TI  - [Education--research: a professorship in nursing].

PMID- 9544118
TI  - [Membership in Norwegian Nurses' Association at any cost?].

PMID- 9544119
TI  - [Snowed under by stress].

PMID- 9544120
TI  - [Family influence greatly exaggerated].

PMID- 9544121
TI  - [Nightmare for the health system].

PMID- 9544122
TI  - [Close-up: Tom Ovlien, editorial secretary for Blikk. Tolerant--yet sharp around
      the edges. Interview by Kari Anne Aase].

PMID- 9544123
TI  - [The normal is problematic. Interview by Kari Anne Aase].

PMID- 9544124
TI  - [My workplace: head nurse surgical department, Kongsvinger Hospital. A hazardous
      position. Interview by Kjell Arne Bakke].

PMID- 9544126
TI  - [Epilepsy--with thunderstorms in the head].

PMID- 9544125
TI  - [From bygone days--social and economic conditions for nurses at the turn of the
      century].

PMID- 9544127
TI  - [Rape--volunteerism for care and support. Interview by Erik Dale].

PMID- 9544128
TI  - [Education--where is "the real life"?. Interview by Erik Dale].

PMID- 9544129
TI  - [History--cut healthy 60 years ago. Interview by Oddrunn Marie Dyrdal].

PMID- 9544130
TI  - [USA--strict demand for licensure. Interview by Jan Erik Andreassen].

PMID- 9544131
TI  - [Care of the elderly: geriatrics--only for those specially interested?].

PMID- 9544132
TI  - [Care for the elderly--elderly persons needing care should select residential
      community carefully].

PMID- 9544133
TI  - [When you have power, you have responsibility!].

PMID- 9544134
TI  - [Home care nursing--when care is experienced as an affront].

PMID- 9544135
TI  - Aortoiliac occlusive disease and gastrointestinal malignancy: changing
      therapeutic options.
AB  - Treatment of gastrointestinal malignancy encountered unexpectedly during
      procedures involving the abdominal aorta continues to be debated. Previously,
      simultaneous vascular procedures with intra-abdominal malignancy were rare. Most
      underwent vascular reconstruction followed by a delayed aortic procedure. With
      recent improvement in axillobifemoral graft patency, a one-stage procedure for
      aortoiliac disease should be entertained. We recently encountered a small bowel
      lymphoma while beginning an aortic replacement for aortic occlusion. Resection of
      a near-obstructing small bowel tumor immediately after axillofemoral
      reconstruction provided treatment of both entities at one time. Since the early
      description of axillofemoral bypass in 1963, varying success with extra-anatomic
      bypass has been reported. Early data for axillofemoral bypass were dismal, but
      with recent technical and graft improvements patency has been improved. Occult
      malignancy during aortic procedures is uncommon, about 2 to 4 per cent, but when
      met is usually dealt with after the patient recovers from the vascular procedure.
      With improvements in extra-anatomic bypass results, a single operative period can
      be entertained.

PMID- 9544136
TI  - Gallbladder diverticulum: a case report and review of the literature.
AB  - Gallbladder diverticulum is an unusual and uncommon disease process rarely
      discussed in the literature. This disorder may not be diagnosed until surgically
      resected. The presentation may entail nonspecific complaints over a prolonged
      period as highlighted in a case report of a 17-year-old woman with this disease.
      The incidence and pathophysiology of this disease process is correlated to the
      symptoms and signs of this patient. The surgical findings, procedure, and outcome
      are described.

PMID- 9544137
TI  - Successful management of visceral Klippel-Trenaunay-Weber syndrome with the
      antifibrinolytic agent tranexamic acid (cyclocapron): a case report.
AB  - Klippel-Trenaunay-Weber syndrome (KTWS) is a rare, congenital disorder
      characterized by vascular nevus formation, deep venous thrombosis, varicosities,
      and hypertrophy of affected tissues. A patient with known thrombosis of his
      splanchnic circulation and visceral KTWS presented with life-threatening
      hemorrhage from rectosigmoid varices. Portosystemic shunting was not feasible.
      Endoscopic sclerosis, variceal ligation, and proctocolectomy were not possible
      due to the size and number of the varices. Previous treatment with epsilon
      aminocaproic acid had been unsuccessful and complicated by thrombophlebitis.
      Conservative treatment with blood transfusions, cryoprecipitate, fresh frozen
      plasma, vitamin K, propanolol, and somatostatin analog failed to stop the
      bleeding. The patient was given the antifibrinolytic agent, tranexamic acid, with
      cessation of his hemorrhage. Serial thromboelastograms confirmed improved
      reaction time, coagulation time, clot formation rate, and maximum amplitude. We
      conclude that tranexamic acid may be a useful adjunct in the medical treatment of
      high-risk patients with KTWS and other vascular nevi complicated by coagulopathy.

PMID- 9544139
TI  - Mucoepidermoid carcinoma of the thyroid gland arising from a papillary epithelial
      neoplasm.
AB  - We report a case of mucoepidermoid carcinoma of the thyroid gland. The
      simultaneous association of papillary and mucoepidermoid carcinoma in a
      Hashimoto's thyroiditis makes the present observation unusual. Surgery was
      limited due to local extension of the neoplasm. The patient consequently
      underwent external radiotherapy followed by radiometabolic therapy. The patient
      survived 11 months after diagnosis. As far as the histogenesis of the neoplasm is
      concerned, we believe that mucoepidermoid areas correspond to squamous and
      mucinous metaplasia of a preexisting papillary carcinoma. Transition areas
      between elements morphologically characteristic of both neoplasms were observed.
      Histochemical and immunohistochemical studies confirmed the diagnosis of a
      carcinoma with multiple aspects showing a focal positive reaction for
      thyroglobulin or keratin antisera. Therefore, this demonstrates different
      functional activities of the neoplastic cells. There is still debate about
      adjuvant therapies, the results of which appear for the moment very poor.

PMID- 9544138
TI  - Ectopic thyroid nodular goiter presenting as a porta hepatis mass.
AB  - An ectopic thyroid goiter was found in a 58-year-old woman who presented with
      abdominal and low back pain, diarrhea, and generalized weakness. Initial workup,
      including abdominal CT scan, revealed a mass extending from the duodenum to the
      porta hepatis. After resection and upon pathologic examination of the tissue,
      nodular arrangement of thyroid follicles and colloid lakes with focal
      hyperplastic and nodular goiter changes were identified.

PMID- 9544140
TI  - Small-bowel perforation secondary to metastatic carcinoma of the breast.
AB  - Perforation from a solitary metastatic lesion of the small bowel is rare. We
      report a case of acute perforation with no evidence of metastatic disease within
      the abdomen. Resection of the small bowel was performed.

PMID- 9544141
TI  - Nonsurgical pneumoperitoneum: a case report and a review.
AB  - The finding of extraluminal gas on plain radiographs is usually associated with a
      perforated viscus. But, as this case shows, the finding of pneumoperitoneum is
      not pathogenic of a perforated viscus or even of a surgical emergency, because
      there are many benign explanations for a pneumoperitoneum. Perhaps the most
      important maneuver for differentiating between the two is by performing a through
      history and physical examination. This in conjunction with either a diagnostic
      peritoneal lavage, contrast studies, or endoscopic evaluation can help prevent a
      patient from having needless surgery. The causes of a nonsurgical
      pneumoperitoneum are described as well as a treatment plan for patients
      presenting with a nonsurgical pneumoperitoneum.

PMID- 9544142
TI  - Atherosclerotic aneurysm of the proximal subclavian artery: a case report.
AB  - Aneurysms of the upper extremities, and particularly the intrathoracic segment of
      the subclavian artery, are unusual. Surgical approach and timing of repair remain
      controversial. We successfully treated a case of a large proximal subclavian
      artery aneurysm, atherosclerotic in origin. In spite of the size, the symptoms
      were vague. The patient underwent partial resection of the lesion located in the
      proximal third of the right subclavian artery, and repair using 8 mm dacron
      interposition graft. She did well postoperatively and remains symptom free at 1
      year. A discussion of this disorder with the relevant literature review is herein
      included.

PMID- 9544143
TI  - Electrophysiologic nerve stimulation for identifying the recurrent laryngeal
      nerve in thyroid surgery: review of 70 consecutive thyroid surgeries.
AB  - To describe a simple technique for identifying the recurrent laryngeal nerve
      (RLN) with a nerve stimulator to prevent damage to the nerve during thyroid
      surgery. A retrospective review of 70 thyroidectomies performed from October 1989
      to January 1995 by one surgeon using electrophysiologic nerve stimulation to
      identify the RLN was conducted. The technique is described. Outpatient flexible
      fiberoptic laryngoscopy was performed preoperatively and postoperatively in all
      patients. From 70 thyroidectomies, 80 RLNs were identified to be at risk for
      injury. Five patients had transient unilateral vocal cord paresis
      postoperatively. No RLN transection or permanent vocal cord paralysis occurred.
      This is the first large series of patients undergoing the use of
      electrophysiologic nerve stimulation for identifying the RLN during thyroid
      surgery. We found the technique to be useful and safe for identifying the RLN. We
      present this technique as a less costly and time-consuming alternative to
      intraoperative RLN monitoring.

PMID- 9544144
TI  - Primary lymphoma of the thyroid.
AB  - Primary lymphoma is an uncommon malignancy of the thyroid, comprising between 0.6
      and 5 per cent of thyroid cancers in most series. This report is presented
      because of a 10 per cent (6 of 60) incidence of this cancer at one institution. A
      short history of a rapidly enlarging neck mass often associated with dyspnea,
      difficulty swallowing, or voice change is the hallmark presentation of thyroid
      lymphoma. The majority of patients are women with a mean age in the 6th decade.
      Although fine-needle aspiration has become the procedure of choice for the
      diagnosis of a thyroid nodule, it has yielded mixed results with the presence of
      lymphoma. The majority of thyroid lymphomas are diffuse, large cell lesions of B
      cell origin. Controversy remains as to the role of surgery in thyroid lymphomas.
      Within the improvement in results with the use of radiotherapy and chemotherapy
      alone or in combination, some authors have advocated relegating surgery to the
      role of diagnosis only. This can be accomplished by fine-needle aspiration, core
      biopsy, or open biopsy. Others have favored a more aggressive surgical approach,
      showing that the amount of residual disease after debulking procedures was
      directly correlated with local and distant recurrences. A lack of randomized
      prospective studies makes it difficult to resolve this issue. The rates of
      complications of surgery, including hypocalcemia and recurrent laryngeal nerve
      damage, are higher than for operations for other types of thyroid malignancy.
      Improved prognosis has been associated with the following factors: disease
      limited to the thyroid, the absence of dysphagia, primary mass less than 10 cm,
      tumors without necrosis, and tumors consisting of plasmacytomas.

PMID- 9544145
TI  - Lower-extremity saphenous vein transposition arteriovenous fistula: an
      alternative for hemodialysis access in AIDS patients.
AB  - Arteriovenous access for long-term hemodialysis in patients with the acquired
      immunodeficiency syndrome (AIDS) represents a special challenge. Many of these
      patients are chronic intravenous drug abusers and do not have patent superficial
      upper-extremity veins available for conventional arteriovenous fistulas. This
      group of patients is also particularly prone to infections, which contraindicates
      the use of prosthetic grafts. Over a period of 13 months, five lower-extremity
      saphenous vein transposition arteriovenous fistulas (SVTAFs) were performed. Four
      patients had a diagnosis of AIDS at the time of operation; all of these were
      intravenous drug abusers. Three patients were male, two were female, and their
      age ranged from 34 to 66 years (mean, 48). Three patients had a SVTAF as their
      first hemodialysis access, and in two it was performed after multiple failed
      upper-extremity accesses. Four fistulas remain patent to date, after a mean
      follow-up of 11 months (range, 4 weeks to 16 months). One fistula thrombosed 4
      weeks postoperatively, due to a hematoma that occurred after premature
      venipuncture for dialysis. There were no other major complications. We conclude
      that SVTAF is a suitable alternative to the limited hemodialysis venous access
      sites, especially in the AIDS population.

PMID- 9544146
TI  - Meandering bullet in the pericardial sac: to remove or not to remove.
AB  - Patients with bullets in the pericardial sac without obvious myocardial injuries
      are rare, making it difficult to analyze the natural history and propose
      management approaches. We present the case of a meandering bullet in the
      pericardial sac and a review of the literature.

PMID- 9544147
TI  - The CVC removal distress syndrome: an unappreciated complication of central
      venous catheter removal.
AB  - The removal of a central venous catheter (CVC) can be complicated by rare but
      potentially life-threatening neurocardiopulmonary distress. The clinical courses
      of eight patients who had CVC removal complications are reviewed. Seven patients
      had catheter removal from the right internal jugular vein, and one from the right
      subclavian vein. The complications occurred after complete removal of the
      catheter (four patients), after guidewire replacement for catheter change (three
      patients), and after detachment of the hemostasis side port of the Swan
      introducer during sheath removal (one patient). Each of them had more than one
      complication. The major complications were: neurologic paresis or coma (four
      patients), respiratory failure (four patients), and shock (two patients). One
      patient died of pulmonary sepsis. The overall mortality rate was 12.5 per cent.
      Guidelines for safe removal of central venous catheters are proposed. Possible
      mechanisms of the complications are discussed. We refer to the observed
      complications as the CVC removal distress syndrome.

PMID- 9544148
TI  - Breaking strength and diameter of absorbable sutures after in vivo exposure in
      the rat.
AB  - Although absorbable sutures are commonly used in clinical practice, the rate of
      decay of strength in various tissues has not been studied. The purpose of this
      study was to assess breaking strength (BS) and diameter of monofilament (chromic
      gut, polydiaxanone, Maxon, Monocryl) and multifilament (Vicryl, Dexon, Polysorb)
      absorbable sutures implanted in various sites and measured at specific time
      intervals. A 15 cm length of 4-0 suture from a single lot of each material was
      implanted in the pleural space, rectus abdominus muscle, subcutaneous tissue,
      intravascular space, peritoneal cavity, and stomach lumen in the rat. A
      precipitous decrease in BS was noted in all multifilament sutures after 7 days,
      and in chromic gut and Monocryl sutures after 1 day. Polydiaxanone and Maxon
      sutures maintained the highest BS over the 28-day period, 71 per cent and 59 per
      cent of their initial BS, respectively. Suture diameter remained essentially
      unchanged except for chromic gut and the multifilament sutures which exhibited
      increased diameter. This increase was attributed to inflammatory tissue
      infiltration.

PMID- 9544149
TI  - Adenocarcinoid tumor of the ampulla of Vater.
AB  - We report a rare case of adenocarcinoid tumor of the ampulla of Vater. The tumor
      contained an intermixture of adenocarcinoma and carcinoid tumor and was removed
      successfully by pancreaticoduodenectomy. The characteristics of these rare tumors
      are reviewed.

PMID- 9544150
TI  - Intrathoracic aberrant thyroid: identification critical for appropriate operative
      approach.
AB  - True aberrant thyroid in the chest is a rarely described entity. More commonly,
      "aberrant" thyroid is a substernal goiter that is an extension of the cervical
      gland inferiorly and can be removed safely with the classic "collar" incision.
      Aberrant intrathoracic thyroid typically derives its blood supply from
      intrathoracic sources and requires an alternate surgical approach for adequate
      exposure. The ability to identify these rare intrathoracic thyroids is critical
      for safe surgical excision.

PMID- 9544151
TI  - The role of liver transplantation in the subacute trauma patients.
AB  - Two case reports are presented involving complex liver traumas requiring the need
      for liver transplantation. Both of these patients were designated unsalvageable
      until the transplant team was consulted. It is imperative that surgeons involved
      with complex hepatic trauma not give up hope and include these patients as
      potential liver recipients when irreversible liver failure occurs.

PMID- 9544152
TI  - A Muir-Torre syndrome family.
AB  - The Muir-Torre syndrome is a rare autosomal-dominant disease involving sebaceous
      neoplasms as markers for multiple internal malignancies. Diagnostic criteria
      include at least one sebaceous gland adenoma, epithelioma, or carcinoma and at
      least one internal malignancy. The world literature contains 162 cases with 316
      internal malignancies. Colorectal and urogenital malignancies predominate, and
      nearly half the patients had two or more internal cancers. The discovery of a
      Muir-Torre syndrome-associated sebaceous lesion is rare and should prompt an
      evaluation for internal malignancies. We report a family over five generations
      displaying this syndrome. The proband is a 44-year-old man with two skin and two
      colon malignancies who presented to our clinic with the chief complaint of an
      infected sebaceous cyst. The world literature is reviewed, and an emphasis on the
      surgeon's role in evaluation and treatment is discussed.

PMID- 9544153
TI  - Muscle-splitting thoracotomy.
AB  - Muscle-splitting thoracotomy avoids transection of the latissimus dorsi and the
      serratus anterior muscles, thereby decreasing post thoracotomy pain and
      preserving the function and viability of these two muscles. The exposure provided
      for most intrathoracic procedures is excellent.

PMID- 9544154
TI  - The anterior extrapleural approach to the thoracolumbar junction revisited.
AB  - General surgeons often provide the exposure for the anterior repair of vertebral
      body lesions. The standard anterior approach to the thoracolumbar junction (T11
      L1) is a transpleural 9th or 10th rib thoracoabdominal incision. From October
      1995 through March 1997, 22 patients underwent anterior repair of thoracolumbar
      junction vertebral lesions through an alternative 11th rib resection while
      maintaining an extrapleural approach. Exposure was excellent, as judged by the
      neurosurgical team completing the repairs. Chest tubes were not used routinely,
      and all patients healed without complications. A major limitation of the 11th rib
      extrapleural approach to the thoracolumbar junction has been poor exposure. This
      problem is eliminated with the use of an abdominal self-retaining retractor
      system. With many potential advantages to this 11th rib exposure (less pain,
      fewer pulmonary problems, and better wound healing), we consider the 11th rib
      incision to be the approach of choice to the thoracolumbar junction and recommend
      renewed interest in this incision.

PMID- 9544156
TI  - Clinical pathways for general surgeons: emergency appendectomy without rupture.

PMID- 9544155
TI  - Howard Christian Naffziger: the surgeon and his syndrome.

PMID- 9544157
TI  - Position statement for the need to define pediatric hematology/oncology programs:
      a model of subspecialty care for chronic childhood diseases. Health Care Policy
      and Public Issues Committee of the American Society of Pediatric
      Hematology/Oncology.

PMID- 9544158
TI  - Efficacy of surveillance radiographic imaging in detecting progressive disease in
      children with advanced stage neuroblastoma.
AB  - PURPOSE: Advanced stage neuroblastoma (NB) is generally associated with a grim
      prognosis. Surveillance radiographic imaging is usually performed frequently to
      detect progressive (PD) or recurrent disease (RD) and promptly begin salvage
      therapy. We studied children with advanced stage NB to determine both how PD or
      RD was detected and the impact of detection in asymptomatic versus symptomatic
      children on outcome. STUDY DESIGN: A retrospective review of children with NB was
      performed between 1984 and 1996. Children with advanced stage NB and RD or PD
      were further studied. RESULTS: Thirty-two children with advanced stage NB and PD
      or RD were identified. The median time to PD or RD after diagnosis was 1 year 2
      months. Nine (28%) children progressed on therapy. One child underwent
      confirmatory biopsy of residual scan abnormalities at the completion of planned
      therapy. Disease recurred in 22 (67%) children after therapy (median time 6
      months). Two children (6%) had RD detected by surveillance studies associated
      only with elevated urinary catecholamines. Despite recent normal studies, 29 of
      32 children (91%) had onset of new symptoms prompting confirmatory radiographic
      studies. CONCLUSIONS: Surveillance radiographic imaging was insensitive in
      detecting PD or RD in children with advanced stage NB. Careful history,
      examination, and selective laboratory evaluation were sensitive and cost
      effective in detecting PD or RD.

PMID- 9544159
TI  - Combined RT-PCR and metaphase-FISH posttransplant studies in pediatric patients
      with chronic myeloid leukemia.
AB  - PURPOSE: To evaluate the use of a combined reverse-transcriptase polymerase chain
      reaction (RT-PCR) and metaphase fluorescent in situ hybridization (FISH) approach
      post-allogeneic marrow transplant in the detection of relapse in pediatric
      patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: Five
      pediatric patients with CML were monitored post-allogeneic transplant (two of
      them also had received donor lymphocyte infusions) using the combined approach of
      RT-PCR and metaphase FISH. Both the transplants and the follow-up were carried
      out in a single institution setting. RESULTS: During the posttransplant
      evaluation, a transiently positive signal for the Philadelphia chromosome but no
      transcription of the bcr/abl-fusion message was detected in one patient currently
      in remission. A posttransplant relapse was detected in two patients who
      demonstrated the Philadelphia chromosome and the bcr/abl-fusion transcript; one
      was successfully treated with donor lymphocyte infusions. The two patients
      consistently negative for both the Philadelphia chromosome and the bcr/abl-fusion
      transcript and currently in remission. CONCLUSION: Pediatric patients with CML
      may transiently demonstrate cells positive for the Philadelphia chromosome but
      not actively transcribing the bcr/abl-fusion message in their marrow during their
      posttransplant evaluation but remain in remission. Recurrence is highly likely in
      patients demonstrating positivity for both; these patients may be considered
      candidates for donor lymphocyte transfusion therapy.

PMID- 9544160
TI  - Identification of (CA/GT)n polymorphisms within the X-linked chronic
      granulomatous disease (X-CGD) gene: utility for prenatal diagnosis.
AB  - PURPOSE: The majority of known female carriers of X-linked chronic granulomatous
      disease (X-CGD), a deficiency of the gp91-phox (phagocyte oxidase) subunit and
      the most common genetic subtype of CGD, are not informative for the linked
      restriction fragment length polymorphisms (RFLPs) described to date. The
      isolation and characterization of two polymorphic (CA/GT)n repeats that lie
      within the X-CGD gene are reported, which are a useful linked marker for prenatal
      diagnosis. PATIENTS AND METHODS: cDNA for gp91-phox was used to probe a genomic
      library. Genomic clones were isolated and screened for (CA/GT)n repeats. The
      repeats were isolated and sequences surrounding the repeats were determined.
      Oligonucleotide primer pairs surrounding the repeats were chosen to facilitate
      polymerase chain reaction (PCR) across the repeat. RESULTS: Analysis of DNA
      derived from over 100 individuals shows both markers to be highly polymorphic
      with a resultant high proportion of heterozygosity in females. Several kindreds
      affected by X-CGD were studied and the (CA/GT)n length polymorphisms were shown
      to segregate with the clinical syndrome or biochemical carrier status. The
      technique was prospectively applied to several kindreds containing a carrier
      mother and an affected child. In a case where a male fetus was shown to carry the
      unaffected allele, the pregnancy was carried to term and the child was not
      affected. CONCLUSIONS: This approach is highly informative in a multiple allele
      system, can provide a technical analysis in just hours, requires only a ng of
      DNA, and permits the transport of diagnostic samples. Therefore, this method can
      be used early in pregnancy on a chorionic villus biopsy sample for prenatal
      diagnosis.

PMID- 9544161
TI  - Clinical value of bone marrow cultures in childhood pure red cell aplasia.
AB  - PURPOSE: We assessed the value of marrow cultures for defining the
      pathophysiology, diagnosis, and therapeutic response to immunosuppressive therapy
      in childhood pure red cell aplasia (PRCA). PATIENTS AND METHODS: Patients were
      evaluated either at diagnosis (n = 23) or at the time of treatment failure (n =
      2). Twelve patients had transient erythroblastopenia of childhood (TEC), 4 had
      Diamont-Blackfan anemia (DBA), and 9 had acquired sustained PRCA (A-Su-PRCA).
      Bone marrow mononuclear cells were cultured with combination of human recombinant
      (rhu) erythropoietin (EPO), granulocyte monocyte colony stimulating factor (GM
      CSF), granulocyte colony stimulating factor (G-CSF), Interleukin 3 (IL-3), either
      with or without stem cell factor (SCF), and burst forming unit of erythroid (BFU
      E) growth was assessed. RESULTS: The combination of growth factors without SCF
      failed to induce any erythropoiesis (BFU-E < 10/10(5) mononuclear cells) in 10
      patients (2 with TEC, 2 with DBA, and 6 with A-Su-PRCA), although the growth of
      erythroid colonies was substantially lower in the remaining patients than in
      controls (45.5 +/- 15.4 versus 91.7 +/- 12.7, p < 0.05). Addition of SCF restored
      erythropoiesis in all but 6 patients (5 with A-Su-PRCA and 1 with DBA). Five of 6
      nonresponders did not respond to any immunomodulating therapy; of the 5, 3 had or
      developed some evidence of myelodysplasia. CONCLUSION: Our data indicate that in
      vitro colony studies might prove to be a useful diagnostic tool, because
      erythropoiesis' poor response to growth factors, including SCF, may suggest the
      diagnosis of myelodysplasia. Moreover, it may have predictive value; in cases of
      PRCA, regardless of etiology, poor growth of erythropoietic colonies may predict
      refractoriness to immunomodulating therapy.

PMID- 9544162
TI  - Postoperative chemotherapy in children less than 4 years of age with malignant
      brain tumors: promising initial response to a VETOPEC-based regimen. A Study of
      the Australian and New Zealand Children's Cancer Study Group (ANZCCSG).
AB  - PURPOSE: Postoperative chemotherapy with indefinite postponement of radiation
      therapy in children < 4 years old with brain tumors was investigated in a multi
      institutional study. PATIENTS AND METHODS: From 1991 to 1995, 42 patients aged 3
      to 47 months (median 20) with brain tumors were enrolled in a 2-phase
      chemotherapy protocol: 16 patients had medulloblastoma (MB); 8 had supratentorial
      primitive neuroectodermal tumor (PNET); 14 had ependymoma; and 4 had other
      tumors. The initial phase was comprised of 4 courses of the 3-drug regimen:
      vincristine (VCR), etoposide (VP-16), and intensive cyclophosphamide (CPA) in a
      previously reported schedule (VETOPEC). The continuation phase was comprised of 2
      drug courses: A, CPA + VCR; B, cisplatin + VP-16; and C, carboplatin + VP-16, for
      a total duration of 64 weeks. RESULTS: Response to VETOPEC was evaluable in 28
      patients with postresection residual (25) and/or metastatic (1 M2, 6 M3) tumor.
      There were 9 complete responses (CR) and 9 partial responses (PR) with a combined
      CR + PR of 64% (95% confidence interval [CI] 44 to 81). In 12 evaluable patients
      with MB, CR + PR was 82% (48 to 98); in 6 patients with PNET, 50% (12 to 88);
      and, in 8 patients with ependymoma, 86% (42 to 99). Of 40 patients eligible for
      further analysis, 6 remain progression-free at a median of 30 months, 14 are
      alive at a median of 38 months, 29 have progressed at a median of 7 months
      (range, 2 to 37 months), and 26 have died. The progression-free and overall
      survival rates at 36 months are estimated to be 11% (95% CI 1 to 22) and 34% (18
      to 50), respectively. CONCLUSIONS: The initial response to the VETOPEC regimen is
      encouraging and warrants study of further dose escalation. Survival remains poor
      with current strategies in this high-risk population.

PMID- 9544163
TI  - Effective adjuvant chemotherapy for advanced nasopharyngeal carcinoma in
      children: a final update of a long-term prospective study in a single
      institution.
AB  - PURPOSE: The purpose of this study was to determine the efficacy and toxicity of
      a doxorubicin/cyclophosphamide-based chemotherapy and local radiation therapy in
      children with locally advanced or metastatic nasopharyngeal carcinoma (NPC).
      PATIENTS AND METHODS: Twelve patients aged 6 to 20 years old were treated with a
      chemotherapy regimen comprised of vincristine (1.5 mg/m2) and doxorubicin (45
      mg/m2) on day 1 and cyclophosphamide (210 mg/m2) and 5-fluorouracil (240 mg/m2)
      on days 1 to 5. Chemotherapy was administered every 3 weeks for 1 to 2 years.
      Radiotherapy to the primary site (59 to 68 Gy) and to the neck (59 to 66 Gy) was
      given before or after 2 to 4 courses of chemotherapy. RESULTS: All patients
      achieved a complete response 4 to 16 months from the start of therapy (median 7
      months). Nine patients have remained tumor free from 2 to 21 years (median 11
      years) from diagnosis. One child was lost to follow-up and one died of
      tuberculosis; both were disease-free. One child developed a secondary
      osteosarcoma in the left mandible. Chemotherapy caused grade 4 neutropenia and
      thrombocytopenia in four patients. There were no therapy-related deaths and the
      most common late effect of therapy was neck fibrosis, which was observed in all
      patients. We conclude that the chemotherapy and radiotherapy regimen used in this
      study is highly effective for children and adolescents with locally advanced NPC
      and is associated with tolerable toxicity.

PMID- 9544164
TI  - In vitro antitumor activity of rebeccamycin analog (NSC# 655649) against
      pediatric solid tumors.
AB  - PURPOSE: This study determined the in vitro antitumor activity of a rebeccamycin
      analog (NSC# 655649) using tetrazolium/formazan (MTT) and clonogenic assays
      against established pediatric cell lines and solid tumor specimens obtained from
      children. MATERIALS AND METHODS: Tumor cells from 14 established cell lines and
      20 patient specimens were exposed in vitro for 1 hour to NSC# 655649 at
      concentrations ranging from 0.015 to 15.0 microM. The cytotoxicity (IC50) of this
      agent against established cell lines was determined using both the MTT
      (cytotoxic) and clonogenic/soft agar cloning (cytostatic) assays. Tumor specimens
      from children undergoing biopsy or surgical resection were also evaluated in
      vitro against NSC# 655649 using the clonogenic assay. For studies using patient
      specimens, antitumor activity was measured by comparing the number of tumor
      colonies from NSC# 655649-treated cells with those from solvent-treated controls.
      RESULTS: These studies showed that the mean IC50S using the MTT and clonogenic
      assays using established solid tumor cell lines were 0.94 and 0.51 microM,
      respectively. In general, for cell lines tested using both types of assays, the
      clonogenic assay resulted in a smaller IC50. The overall in vitro responses (< or
      = 50% survival compared to controls) using patient tumor specimens and the
      clonogenic assay were 35% (1.5 microM), 60% (7.5 microM), and 80% (15.0 microM).
      Of the 9 patients with neuroblastoma, responses to NSC# 655649 were seen in 33%
      (1.5 microM), 58% (7.5 microM), and 92% (15.0 microM) of the specimens. Prior
      chemotherapy did not appear to adversely affect in vitro responses. CONCLUSIONS:
      NSC# 655649 appears to have broad antitumor activity in vitro against pediatric
      malignancies at drug concentrations achieved during adult phase I clinical
      trials. These studies support the further development of NSC# 655649 for solid
      tumors in children.

PMID- 9544165
TI  - Blunted serum erythropoietin response to anemia in patients polytransfused for
      beta-thalassemia major.
AB  - PURPOSE: To investigate the response of erythropoietin (EPO) to anemia in
      patients polytransfused for beta-thalassemia major. PATIENTS AND METHODS: We
      measured the serum EPO levels and the concurrent hemoglobin (Hb) concentrations
      in 40 patients polytransfused for beta-thalassemia major, in 18 patients with
      iron deficiency anemia (IDA), and 32 healthy subjects. Serum EPO levels were
      assayed by an enzyme immunoassay. RESULTS: In both groups with beta-thalassemia
      major and IDA, serum EPO levels were significantly elevated (114 +/- 71 and 239
      +/- 217 mU/mL, respectively). There was a significant inverse correlation between
      log EPO values and Hb concentrations in patients with beta-thalassemia major (r =
      0.61; p < 0.01) and IDA (r = 0.81; p < 0.01). In a semilogarithmic plot, the
      slope of the regression line obtained in patients with beta-thalassemia major was
      significantly lower than that of IDA (p < 0.01), suggesting a blunted EPO
      response to anemia in patients polytransfused for beta-thalassemia major. The
      elevation of serum EPO in patients with beta-thalassemia major was poorly related
      to clinical variables except serum ferritin. CONCLUSIONS: We conclude that a
      significant inverse relationship between serum EPO levels and Hb concentration
      exists in patients with beta-thalassemia major. However, this EPO response in
      patients with anemia caused by beta-thalassemia major may be blunted when
      compared to patients with IDA.

PMID- 9544166
TI  - Donor lymphocyte infusions to displace residual host hematopoietic cells after
      allogeneic bone marrow transplantation for beta-thalassemia major.
AB  - PURPOSE: Donor lymphocyte infusion (DLI) was used to reverse relapse after
      allogeneic bone marrow transplantation (BMT) in a patient with beta-thalassemia
      major. PATIENTS AND METHODS: The patient with unstable mixed chimerism after BMT
      was treated with graded increments of donor lymphocytes (10(5) T cells/kg to 5 x
      10(7) T cells/kg) to displace residual hematopoietic host cells. RESULTS: DLI
      resulted in complete donor-derived reconstitution of the hematopoietic
      compartment. The patient developed mild graft-versus-host disease (GVHD) that
      could be controlled by steroid treatment. CONCLUSIONS: This case report shows
      that DLI can effectively eradicate host stem cells in mixed chimeras after BMT in
      nonmalignant hematopoietic diseases.

PMID- 9544168
TI  - Phenytoin-induced thrombocytopenia treated with intravenous immune globulin.
AB  - PURPOSE: To describe the use of intravenous immune globulin (IVIG) in an 8-year
      old girl with phenytoin-induced thrombocytopenia and leukopenia. PATIENTS AND
      METHODS: An 8-year-old girl had fever, rash, thrombocytopenia, and leukopenia 18
      days after initiation of phenytoin therapy. The phenytoin level was elevated. She
      was treated with 1 g/kg of IVIG. RESULTS: The thrombocytopenia improved
      dramatically after IVIG therapy. There was a slower response to the leukopenia.
      CONCLUSIONS: Phenytoin hypersensitivity can present with thrombocytopenia and
      leukopenia. Treatment with IVIG was associated with a rapid rise in the platelet
      count in the patient in this report. IVIG should be considered for patients with
      phenytoin-induced thrombocytopenia.

PMID- 9544167
TI  - Hemolytic anemia associated with cold agglutinin during chickenpox and a review
      of the literature.
AB  - PURPOSE: To describe the findings and cause of anemia and jaundice in a 2-year
      old boy. PATIENT AND METHODS: This boy was admitted with a hemoglobin of 7.8
      g/dL, a bilirubin of 1.8 mg/dL, and increased urobilinogen. RESULTS: On the
      second day after admission, hemolytic anemia associated with an anti-I cold
      agglutinin was diagnosed, which was transient and recovered without any
      treatment. CONCLUSION: This is a very rare complication of chickenpox; only five
      cases have been previously reported and these were all characterized by anti-Pr
      cold agglutinin with hemolytic anemia after the onset of chickenpox. We report
      the first case of hemolytic anemia associated with an anti-I cold agglutinin
      during the incubation period of chickenpox.

PMID- 9544169
TI  - Pregnancy during therapy for childhood acute lymphoblastic leukemia: two case
      reports and a review of the literature.
AB  - PURPOSE: The incidence and consequences of pregnancy during therapy for childhood
      acute lymphoblastic leukemia (ALL) are largely unknown. To explore the issues
      involved in this complication of ALL treatment, two recent cases are presented.
      PATIENTS: Two 15-year-old girls with "high risk" ALL became pregnant while
      receiving maintenance therapy. RESULTS: In one case, the patient experienced a
      spontaneous abortion at approximately 5 to 6 weeks gestation. The patient
      completed maintenance therapy and is in remission 8 months after the end of
      treatment. The second patient, known to be non-compliant during therapy, was
      found to be 5 months pregnant at the end of maintenance therapy. She developed
      HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), was
      induced at approximately 34 weeks, and delivered an apparently normal baby girl.
      Both the patient and her baby continue to do well 10 months after delivery.
      CONCLUSIONS: A variety of factors may influence the incidence of pregnancy during
      ALL therapy. Gonadal function, which is likely to return to normal during
      maintenance therapy, may also be affected by alterations in the dose intensity of
      treatment. Social factors may also alter the incidence of pregnancy. Adverse
      effects on the fetus are more likely to occur in the first trimester, depending
      on the drug or drugs used. Although all chemotherapies may have mutagenic and
      teratogenic effects, they do not invariably cause abnormalities. Survival of
      adolescents who become pregnant during treatment does not appear to be adversely
      affected when therapy is not modified or discontinued.

PMID- 9544170
TI  - Spindle cell sarcoma of the kidney with ganglionic elements (malignant
      ectomesenchymoma) associated with chromosomal abnormalities and a review of the
      literature.
AB  - PURPOSE: Malignant ectomesenchymomas are tumors that exhibit both mesenchymal and
      neuroectodermal elements (1). We report a case thought to represent a malignant
      ectomesenchymoma arising in the kidney with cytogenetic abnormalities that may
      provide insight into the biologic basis for this unusual tumor. METHODS: We
      discuss the clinical features, histopathologic findings, cytogenetics, treatment,
      and outcome of a child with a malignant ectomesenchymoma arising in the kidney.
      RESULTS: An asymptomatic 16-month-old boy had a large abdominal mass. The
      resected tumor contained sheets of spindled cells that expressed mesenchymal
      markers and cartilaginous differentiation, interspersed with clusters of ganglion
      cells that expressed neural markers. No blastemal or epithelial elements were
      demonstrated. Cytogenetic analysis of the tumor revealed a hyperdiploid count
      with multiple numerical and structural abnormalities, including a translocation
      between chromosomes 12 and 15. In addition to the surgical resection, the patient
      was successfully treated with adjuvant chemotherapy and local radiation therapy.
      CONCLUSION: This is the first report of which we are aware of an ectomesenchymoma
      arising within the kidney. A subset of malignant ectomesenchymomas may be related
      to the Ewing's family of tumors (EFTs) (2), but this case did not exhibit
      cytogenetic features consistent with EFT. Thus, the malignant ectomesenchymoma
      phenotype probably represents a heterogeneous group of tumors with different
      genotypes and origins. Cytogenetic analysis may be instrumental in determining
      the appropriate therapeutic approach when faced with such a neoplasm. The
      outcomes of 12 other children with ectomesenchymoma are reviewed.

PMID- 9544171
TI  - Clear cell sarcoma of the kidney: an unusual presentation and review of the
      literature.
AB  - PURPOSE: To describe a child with clear cell sarcoma of the kidney (CCSK) with an
      unusual presentation, including a primary tumor of the left kidney with
      metastases to the right kidney and soft tissues of the lower extremities, and to
      review the literature. PATIENT AND METHODS: An 8-month-old infant presented with
      hypertension, an abdominal mass, and soft tissue masses in the left thigh and
      right foot. Imaging studies revealed a large left-sided renal tumor, left
      paravertebral soft tissue masses, and left thigh mass. At laparotomy, a lesion
      was noted in the lower pole of the contralateral kidney. CCSK with metastases to
      the contralateral kidney and to the soft tissues of left thigh, right foot, and
      left paravertebral region was diagnosed on histopathologic examination. RESULTS:
      Multimodal oncologic treatment included surgery, chemotherapy, and radiotherapy.
      Three months after completion of therapy, a soft tissue lesion in the left arm
      and, later, soft tissue lesions involving multiple parts of the body developed.
      The patient died 18 months after diagnosis without clinical or radiographic
      evidence of bone involvement. CONCLUSIONS: In a review of the literature, CCSK is
      most commonly associated with bone and lung metastases. Soft tissue involvement
      is uncommon. Metastasis to the contralateral kidney at initial diagnosis has not
      previously been reported. This case represents an unusual metastatic pattern of
      CCSK.

PMID- 9544172
TI  - Nongestational choriocarcinoma in the postpartum period: a case report.
AB  - PURPOSE: To determine the tissue of origin (gestational versus nongestational) of
      an extensive metastatic choriocarcinoma in an 18-year-old woman to determine
      prognosis and treatment. METHODS: DNA microsatellite polymorphisms after
      polymerase chain reaction (PCR) amplification of the tumor tissue and blood from
      the patient, husband, and daughter were used to determine the tissue of origin.
      RESULTS: Molecular analyses revealed that the tumor shared the genetic features
      of only the patient. She responded well to multiagent chemotherapy. CONCLUSIONS:
      Molecular analysis is a useful tool to determine whether a choriocarcinoma
      occurring in a female patient of child-bearing age is gestational or
      nongestational when clinical findings are not clearly indicative of the primary.

PMID- 9544173
TI  - Upstaging of non-Hodgkin's lymphoma in a child based on 67Gallium scintigraphy.
AB  - PURPOSE: To describe a patient whose non-Hodgkin's lymphoma (NHL) appeared to be
      localized by standard modalities but who was upstaged after Gallium scintigraphy
      suggested disseminated disease. PATIENT AND METHODS: A patient with biopsy proven
      NHL in the maxillary sinus was staged as having localized disease based on
      computed tomography (CT) scans, bone scintigraphy, and evaluation of bone marrow
      and spinal fluid. Open biopsy of a bony lesion, standard modalities for lymphoma
      staging, and Gallium scintigraphy were obtained. RESULTS: Gallium scanning showed
      bony lesions not previously seen with the standard modalities. Open biopsy of one
      of these lesions confirmed disseminated disease. CONCLUSIONS: Gallium scanning
      aids in the early identification of metastases in some patients with NHL and
      should be included in a standard evaluation of apparently localized disease.

PMID- 9544174
TI  - Ewing's tumor and papillary adenocarcinoma of the thyroid in a 14-year-old girl.
AB  - PURPOSE: We describe an adolescent girl with Stage 1 Ewing's tumor and localized
      papillary adenocarcinoma of the thyroid gland, a previously unreported
      association. PATIENTS AND METHODS: A 14-year-old girl with right axillary
      adenopathy was evaluated. RESULTS: Ewing's tumor was diagnosed after a lymph node
      biopsy. A magnetic resonance imaging scan of the axilla, chest wall, and neck
      demonstrated a nodule in the right lobe of the thyroid gland. A biopsy revealed
      papillary adenocarcinoma. CONCLUSIONS: This is the first report of Ewing's tumor
      and carcinoma of the thyroid in the same patient.

PMID- 9544175
TI  - Highly probable anaphylactic reaction to systemic thrombolytic therapy with high
      dose urokinase in a child with a prosthetic valve.

PMID- 9544176
TI  - Pediatric residency training in an era of managed care: an introduction to
      proceedings of a national conference.
AB  - On May 4, 1996, a conference sponsored jointly by the Division of Medicine of the
      Health Resources and Services Administration and the Ambulatory Pediatric
      Association brought together pediatric educators from academic medical centers
      and managed care organizations to address the challenges and opportunities for
      pediatric residency training, given current trends toward increasing managed care
      for children. This supplement is designed to bring the issues discussed there to
      a broader audience of pediatricians and educators. The contributions are written
      by the participants of that conference, with invited commentaries to add
      additional perspectives on each topic. The papers were reviewed by an editorial
      board of leaders in pediatric education with experience in relevant areas. This
      introduction describes the impetus for the conference and highlights a number of
      critical issues facing pediatric postgraduate training that are presented in
      greater depth in the contributions that follow. Finally, this paper summarizes
      the recommendations of the conference for meeting the challenges of training
      pediatricians in these areas.

PMID- 9544177
TI  - Pediatric education and managed care: a literature review.
AB  - Managed care is becoming the dominant form of health care delivery and financing
      in the United States, necessitating changes in pediatric education. This
      transition is redefining the questions of what needs to be taught, who should be
      teaching it, where it should be taught, and how to pay for this education. We
      performed a literature review and examined reports from policy and professional
      groups to seek answers to these questions. We have identified curricular,
      administrative, and financial challenges to pediatric education in managed care.
      Although road maps for innovation have been described, there is a deficiency of
      research and information in key areas of pediatric education in the managed care
      environment.

PMID- 9544178
TI  - Child health care in changing times.
AB  - Unprecedented transformations in the financing and organization of child health
      care are driving change in the practice of pediatrics at a remarkably fast pace.
      The health care needs of children also are evolving, reflecting changing disease
      patterns, new technologies, and shifting socioeconomic and demographic
      characteristics of children and families. Changes in the financing and
      organization of child health services catalyzed by managed care and legislative
      initiatives need to be responded to proactively by the pediatric community. Yet,
      the anticipated health care needs of children also must be addressed as models
      for both pediatric training and practice in the future are developed. This
      article summarizes briefly these changes in health care services and in child
      health needs, addresses training implications, and discusses several initiatives
      the pediatric community is undertaking to develop guidelines for training
      pediatricians for the 21st century.

PMID- 9544179
TI  - Developing models for pediatric residency training in managed care settings.
AB  - The preparation of pediatric residents to function optimally in managed care
      environments challenges educators to create a new set of educational objectives
      and competencies and to incorporate these into curricula that are already full.
      Many of the skills needed to practice managed care are those that have been
      required for the practice of pediatrics in any setting. Nevertheless, the
      emergence of managed care requires the identification of new knowledge to be
      acquired and new skills and attitudes to be incorporated into daily practice.
      These competencies can be identified most thoroughly through collaboration among
      physicians, educators, and leaders of managed care organizations. This joint
      effort should also serve to establish a foundation on which collaborative,
      mutually beneficial learning environments can be created. The development of
      curricula that provide the opportunities needed to attain managed care
      proficiencies requires an individualized approach for each program that takes
      into account the degree of managed care penetration in each training environment.
      Programs in which a managed care approach to patient care predominates will be
      able to promote most easily their trainees' incorporation of these principles
      into routine practice. Those with less regular exposure will be forced either to
      promote managed care principles in an environment in which they may not be
      accepted or practiced, or to join in partnership with managed care organizations
      (MCOs) to train residents. Regardless of the setting, evaluation methodologies
      must be developed to ensure that each of the core competencies has been learned,
      can be applied to clinical situations, and is retained throughout the training
      period. These efforts require the development of faculty who understand and can
      model a managed care approach to patient management. The ongoing evolution of
      managed care systems encourages the development of new, creative strategies to
      train faculty, who may find themselves learning about this emerging environment
      at the same time as are their trainees.

PMID- 9544180
TI  - Teaching clinical decision-making to pediatric residents in an era of managed
      care.
AB  - The growth of managed care has brought a new focus on physician competency in the
      appropriate use of resources to help patients. The community of pediatric
      educators must improve residency curricula and teaching methodologies to ensure
      that graduates of their programs can effectively and efficiently meet the needs
      of children and their families. The educational approach in many pediatric
      residency programs is an implicit apprenticeship model, with which the residents
      follow the actions of attending physicians with little attention to scrutiny of
      the clinical evidence for and against diagnostic and treatment strategies.
      Evidence-based medicine stresses to the trainee the importance of the evaluation
      of evidence from clinical research and cautions against the use of intuition,
      unsystematic clinical experience, and untested pathophysiologic reasoning as
      sufficient for medical decision-making. Managed care also has helped to create a
      heightened awareness of the need to educate residents to incorporate the
      preferences of patients and families into diagnostic and treatment decisions.
      Trainees must know how to balance their duty to maximize the health of
      populations at the lowest resource use with their duty to each individual patient
      and family. Changes in the residency curriculum will bring change in educational
      settings and the structure of rotations. Potential barriers to implementation
      will include the need for faculty development and financial resources for
      information technology.

PMID- 9544181
TI  - Continuous improvement learning for residents.
AB  - Physicians must be ready to assume an active role in the design, implementation,
      and improvement of emerging models of health care delivery. Knowledge and skill
      in continuous improvement prepare them to engage seriously in the processes of
      change, on the basis of the same scientific principles they always have relied on
      in the use of evidence to improve outcomes. This includes include the ability to
      1) identify the health needs of the individuals and communities for which they
      provide health services; 2) assess the impact of current practice with
      appropriate outcome measures; 3) discover what in the process of health care may
      be contributing to less than desired outcomes; 4) design and test interventions
      to change the process of care to improve outcomes; 5) act as an effective member
      of the interdisciplinary team required to complete these tasks; and 6) consider
      ethical principles and professional values when making decisions about change in
      health services delivery. Graduate medical education presents special
      opportunities and challenges for learning about continuous improvement. Early
      experiences at Rainbow Babies and Children's Hospital in Cleveland and Children's
      Hospital in Boston suggest how we might prepare pediatricians and other
      physicians to create positive change and continually improve health care.

PMID- 9544182
TI  - General pediatric teaching clinics and managed care.
AB  - Academic general pediatric divisions can function as effective primary care
      providers in a managed care environment. Residents training in these programs are
      expected to be better equipped to enter a work environment that is increasingly
      structured in a managed care format. Positive and negative consequences of
      managed care in an academic setting are discussed. Recommendations for successful
      implementation of resident training in the world of managed care are shared.

PMID- 9544183
TI  - Training pediatricians for the evolving generalist-specialist interface in the
      managed care era.
AB  - Managed care involves the linkage of service delivery and financing. One of the
      outgrowths of the rapid expansion of managed care over the past decade has been
      an increasing consensus that the generalist of the future will need to manage
      more of the patients traditionally cared for by subspecialists. Subspecialty
      education for pediatric residents becomes increasingly important as the role of
      the pediatric generalist enlarges to include independent outpatient management of
      some less complex but traditional subspecialty patients as well as collaborative
      management of more complex patients. To prepare for this role, a balanced
      exposure to subspecialty problems in outpatient as well as inpatient settings is
      required. At the same time, however, the growth of managed care has led to
      certain barriers for providing this enhanced training. This article describes the
      effects of managed care on the role and scope of the pediatric subspecialist as
      well as on educational strategies for coping with these changes while reshaping
      the roles of both generalists and subspecialists for maximal effectiveness in
      meeting the health care needs of children.

PMID- 9544184
TI  - The impact of graduate medical education financing policies on pediatric
      residency training.
AB  - OBJECTIVE: To review special issues related to pediatric residency training in
      managed care organizations, the effects of the changing health care system on the
      demand for pediatricians and the potential impact on financial support for
      residency training, current methods of financing graduate medical education
      (GME), possible future approaches to financing GME, and policy directions to
      support training of pediatricians well prepared for future practice. METHODS: We
      reviewed current information on residency education in managed care settings,
      including the rationale for training in such settings and the realities of such
      educational experiences. We then assessed the evidence concerning the supply and
      demand for pediatricians in the present health care marketplace, with its
      evolution to managed systems of health care. We summarized current approaches to
      financing GME through Medicare, Medicaid, private insurers and purchasers, and
      direct federal and state support, with emphasis on the financing of ambulatory
      training which could occur in managed care settings. Lastly, we described factors
      influencing the upcoming revolution in GME financing and outlined possible new
      policy directions for the financing of relevant GME training experiences.
      RESULTS: Appropriate training experiences in managed care organizations may be a
      valuable strategy to address the current disconnect between the traditional
      hospital-based education of pediatricians and the expanded competencies necessary
      to practice in intensively managed, integrated and accountable health systems.
      Present pediatrician supply appears to be in relative balance with health
      maintenance organization staffing patterns and with needs-based requirements
      estimates. However, the pediatrician-to-child population ratio is predicted to
      increase rapidly over the next decade, leading to an oversupply of pediatricians
      under likely future health care delivery system scenarios. Medicare is the
      largest explicit payer of GME training costs, historically directing
      reimbursement primarily for hospital-based education. Numerous innovative
      financing strategies are being considered to facilitate funding of GME training
      in ambulatory settings and to open up funding to greater public scrutiny and
      accountability. CONCLUSIONS: Although reforms in federal GME financing have been
      limited to date and other significant changes have been largely state-based, it
      is likely in the future that explicit funds will be targeted to specialties in
      demand that prepare physicians well for future practice. Pediatricians and
      medical educators must intensify their voices in the financing debate to ensure a
      productive future for quality pediatric residency training.

PMID- 9544185
TI  - The changing health care environment: implications for residency training.
AB  - Throughout the United States, the growth of managed care is forcing pediatric
      providers (physicians and hospitals) to reconstruct and integrate the health care
      delivery system with a focus away from the academic center and toward the
      community. Managed care also is forcing new financing approaches geared toward
      the assumption of economic risk for patient management and utilization of
      services. Radical changes in pediatric training programs will be necessary to
      accommodate the strategic and operational changes being pursued in response to
      these evolving market forces. These changes, while disruptive, will strengthen
      the breadth and diversity of graduate medical education and will better prepare
      trainees for the new delivery system in which they will practice. In this
      article, we examine how the evolution of managed care is redefining the basic
      financial and organizational framework for pediatric care and the implications of
      this redefinition for children's hospitals and academic medical center-based
      pediatric programs. We draw on our experience in the greater Philadelphia market
      to illustrate the impact of these changes and discuss one pediatric system's
      response. Finally, we review the educational opportunities provided by these
      changes.

PMID- 9544186
TI  - Organizational responses to managed care: issues for academic health centers and
      implications for pediatric programs.
AB  - The health care market dynamics that supported and directed the growth and
      development of Academic Health Centers (AHCs) have changed dramatically in the
      last 10 years. AHCs are struggling to adapt to new reimbursement mechanisms and
      to compete effectively for limited dollars, but are constrained by administrative
      and governance structures that are slow to evolve. Their multiple missions,
      including education, research, and care for complex patients and underserved
      populations, are at risk. Although most recognize the need for substantive
      reorganization, available resources and market specifics vary dramatically from
      one AHC to another. The current approaches to adaptation by four AHCs are
      described, along with some of the unique challenges confronted by academic
      pediatric programs.

PMID- 9544187
TI  - Phenolphthalein: a sheep in wolf's clothing?

PMID- 9544188
TI  - Psoralen photochemotherapy, clinical efficacy, and photomutagenicity: the role of
      molecular epidemiology in minimizing risks.
AB  - Photochemotherapy employing 8-methoxypsoralen and ultraviolet radiation (PUVA) is
      widely used in the treatment of psoriasis. The photoactivation of psoralens in
      skin cells leads to DNA photoadduct formation which may be responsible for the
      efficacy of PUVA. Subsequent mutations may lead to the increased incidence of
      squamous cell carcinoma (SCC). Mutations in the p53 tumor suppressor gene have
      been detected in many human cancers. In this review, p53 mutation spectra in
      murine and human SCC are compared to those obtained from murine cells and skin
      treated with PUVA as well as to the p53 mutation spectrum in human solar SCC.
      While the expected psoralen-type mutations at alternating AT sites were detected
      in the treated cells and murine SCC (average frequency > 40%), such mutations
      were not commonly detected in the human SCC (< 10%). Other common mutations in
      the human SCC included: CG-->TA transitions (18%) and CG-->AT and TA-->GC
      transversions (17 and 25%, respectively). In addition, the frequency of UVB-type
      mutations at dipyrimidine sites (CC-->TT) in the SCC PUVA-treated psoriasis
      patients was comparable to that in patients with SCC from only solar exposure. A
      review of therapeutic history of these patients showed that many had also
      received UVB phototherapy. Furthermore, because sunlight is thought to be
      beneficial for psoriasis, nontherapeutic, casual UVB exposure cannot be excluded.
      Thus, the PUVA SCC may have arisen from the solar mutations and PUVA may enhance
      tumor progression by other epigenetic effects.

PMID- 9544189
TI  - Measurement of micronucleated erythrocytes and DNA damage during chronic
      ingestion of phenolphthalein in transgenic female mice heterozygous for the p53
      gene.
AB  - Phenolphthalein, a common ingredient in nonprescription laxatives and a multisex,
      multispecies rodent carcinogen, was evaluated under chronic exposure conditions
      for genotoxicity in transgenic female mice heterozygous for the p53 gene
      (heterozygous TSG-p53 mice). Phenolphthalein was administered in the diet at 200,
      375, 750, 3,000, and 12,000 ppm (corresponding to a time-weighted average of 37,
      71, 146, 569, and 2,074 mg/kg/day, respectively) for 6 months (183 days). On days
      39, 92, 137, and 183 of treatment, peripheral blood samples were collected and
      evaluated for the frequency of micronucleated polychromatic and normochromatic
      erythrocytes (MN-PCE and MN-NCE, respectively), the percentage of PCE (%PCE)
      among total erythrocytes, and the extent of DNA damage (single strand breaks,
      alkali labile sites, DNA crosslinking) in leukocytes. In addition, the extent of
      DNA damage was evaluated in liver parenchymal cells sampled from mice at the end
      of the 6-month treatment period. DNA damage was evaluated using the alkaline (pH
      > 13) Single Cell Gel (SCG) assay. In addition, using a modified SCG technique,
      the frequencies of leukocytes and liver parenchymal cells with extremely low
      molecular weight DNA (indicative of apoptosis and/or necrosis) were determined.
      At each sample time, phenolphthalein induced a highly significant, dose-dependent
      increase in the frequency of MN-PCE and MN-NCE and in %PCE. Maximal induction of
      MN-PCE and %PCE decreased with increasing treatment duration, most likely due to
      a treatment duration-dependent decrease in the relative amount of ingested
      phenolphthalein. A comparative analysis of the kinetochore status of MN in
      erythrocytes sampled from control mice and mice ingesting phenolphthalein at
      12,000 ppm for 183 days indicates that the induced MN resulted predominantly but
      not exclusively from numerical chromosomal damage. The analysis for increased
      levels of DNA damage in blood leukocytes was inconclusive, with a small but
      statistically significant increase in DNA migration on days 39 and 137 but not on
      days 92 and 183. The extent of DNA migration in liver parenchymal cells sampled
      from mice at the end of treatment was not altered significantly. The frequencies
      of apoptotic and/or necrotic leukocytes and liver parenchymal cells were not
      increased among mice ingesting phenolphthalein. The lowest effective dose at
      which a significant genotoxic response (i.e., the induction of MN-NCE) was
      detected was 200 ppm, the lowest dose tested in this study. This dose in mice is
      comparable to doses (on a mg/m2 basis) experienced by humans.

PMID- 9544190
TI  - Epididymal sperm aneuploidies in three strains of rats detected by multicolor
      fluorescence in situ hybridization.
AB  - A multicolor fluorescence in situ hybridization (FISH) method was developed to
      detect aneuploidy and diploidy in epididymal sperm of rats using DNA probes
      specific for chromosomes 4 and Y. Fourteen healthy young-adult rats from three
      strains were evaluated: inbred Fisher 344/N/ehs, outbred Sprague-Dawley, and
      outbred WU Wistar/CPB. The hybridization efficiency of the FISH procedure was >
      99.9%, the sex-ratio in sperm was approximately 1 as expected, and there was no
      significant variation among two independent scorers. No significant variations
      were detected within or among strains in the frequencies of sperm disomy for
      chromosome 4 (1-6.5 per 10,000 cell per animal) or the Y chromosome (0-2.5 per
      10,000 cells per animal). There was a trend toward increased variation among
      Wistar rats. The frequencies of sperm-carrying hyper- and hypohaploidy for
      chromosome 4 were similar, suggesting a symmetrical mechanism of chromosome gain
      and loss during meiosis. The frequencies of Y-Y-4-4 sperm, which represent
      genomic meiosis II errors, did not differ significantly across strains (0.1-0.7
      per 10,000 cells per strain). This FISH method for detecting aneuploidy in rat
      epididymal sperm provides a promising interspecies biomarker of male germ cell
      aneuploidy and introduces the rat as an animal model for investigating the
      heritable risk to offspring associated with paternal genotype, physiology, and
      exposure to environmental mutagens. There appear to be no significant differences
      among young healthy rats, mice, and men in the baseline frequencies of sperm with
      Y chromosomal disomy, the only chromosome for which data currently exists for all
      three species.

PMID- 9544191
TI  - Apoptotic response of spermatogenic cells to the germ cell mutagens etoposide,
      adriamycin, and diepoxybutane.
AB  - In testis, apoptosis is a way to eliminate damaged germ cells during their
      development. In this study, we evaluated the ability of three germ cell mutagens
      to induce apoptosis (or programmed cell death) at specific stages of rat
      seminiferous epithelial cycle. These chemicals include the cancer chemotherapy
      drugs etoposide and adriamycin and the butadiene metabolite diepoxybutane.
      According to our results, etoposide is a very potent inducer of apoptosis in male
      rat germ cells and the cell types most sensitive to it include all types of
      spermatogonia, zygotene, and early pachytene spermatocytes and meiotically
      dividing spermatocytes. Also, adriamycin causes an increase in apoptosis at
      specific stages of seminiferous epithelial cycle and the most sensitive cell
      types are type A3-4 spermatogonia, preleptotene, zygotene, and early pachytene
      spermatocytes. Diepoxybutane does not cause any significant increase in the
      frequency of apoptosis in rat testis. In addition, we studied whether p53 is
      taking part in the apoptotic response of spermatogenic cells by studying the
      levels of p53 protein in testis before and after chemical treatment. No
      accumulation of p53 in testis was seen after treatment with these three
      chemicals. The expression of two p53-regulated genes, p21WAF1 and mdm2, was also
      studied but no increase in the levels of mRNA of these genes was observed after
      treatment. The results indicate that apoptosis should be taken into consideration
      when the genotoxic effects of chemicals are evaluated in germ cells.

PMID- 9544192
TI  - Comparison of the types of mutations induced by 7,12-dimethylbenz[a]anthracene in
      the lacI and hprt genes of Big Blue rats.
AB  - An important question regarding the use of transgenic reporter genes to detect
      mutation in rodents is how the types of mutations recovered in transgenes compare
      with the types of mutations found in endogenous genes. In this study, we examined
      mutations induced by 7,12-dimethylbenz[a]anthracene in the lacI transgene and the
      endogenous hprt gene of lymphocytes from Big Blue rats and in the hprt gene of
      lymphocytes from nontransgenic Fischer 344 rats. The overall mutation profiles
      found in these genes were remarkably similar: the majority of mutations were base
      pair substitutions, with the most common mutation being A:T-->T:A transversion.
      Differences were found for the mutational profiles in the endogenous gene and
      transgene with respect to the location of the mutations and the orientation of
      basepair substitutions in the DNA strands. In most cases, these differences could
      be explained by the nature of the target genes. The results support the use of
      the lacI transgene for detecting in vivo mutation.

PMID- 9544193
TI  - Effects of germanium oxide and other chemical compounds on phenylmercury acetate
      induced genotoxicity in cultured human lymphocytes.
AB  - Phenylmercury acetate (PMA), which not only causes an elevation of sister
      chromatid exchanges (SCEs) but also induces high frequency of endoreduplication
      in human lymphocytes, may be genotoxic to humans. The major aim of our study was
      to investigate the effects of germanium oxide (GeO2), D-penicillamine (D-PA),
      dimercaprol (BAL), and diltiazem (DTM) on PMA-induced genotoxicity as quantified
      by SCEs. All concentrations of the four chemical compounds tested alone did not
      induce genotoxicity in cultured human lymphocytes. However, GeO2 significantly
      inhibited PMA-induced genotoxicity in a concentration-dependent manner.
      Similarly, D-PA at concentrations of 3 microM and 10 microM, and BAL at a
      concentration of 30 microM produced the antigenotoxic effects. In addition, GeO2
      (1.5 microM) significantly reversed an increase of endoreduplication frequency
      caused by PMA. In a cell cycle kinetic study, GeO2 (0.5-5.0 microM) reversed the
      inhibition of PMA on the proliferating rate index (PRI) of lymphocytes. On the
      contrary, both D-PA and DTM at concentrations of 30-300 microM markedly
      potentiated PMA-induced inhibition of PRI. These findings show that GeO2, D-PA
      and BAL could antagonize PMA-induced genotoxicity, and GeO2 appears to be the
      most effective.

PMID- 9544194
TI  - Formation of direct-acting mutagens from mixtures of N-nitrosomorpholine and
      carboxylates by UVA irradiation.
AB  - Previously, we found that a directly mutagenic compound is produced from N
      nitrosopiperidine (NPIP) in phosphate buffer on exposure to near-ultraviolet
      light (UVA) and we identified its structure as alpha-hydroxy-N-nitrosopiperidine
      phosphate ester. In the present study, we show that a similar photoactivation of
      an N-nitrosamine can take place with carboxylates in place of phosphate. When a
      neutral solution of a mixture of N-nitrosomorpholine (NMOR) and sodium acetate
      was irradiated with UVA, the solution became directly mutagenic towards
      Salmonella typhimurium TA1535. O6-Alkylguanine-DNA alkyltransferase-deficient
      strains of S. typhimurium showed remarkably higher mutagenesis responses to this
      mutagen than the proficient strains. Citrate, succinate, and several other
      biological carboxylates were also effective in producing the mutagens. Since a
      treatment of the "NMOR plus acetate" photoproduct with carboxylic ester hydrolase
      resulted in a loss of the mutagenicity, the active principle is suggested to be
      an acetate-esterified derivative of NMOR. The role of the esters as intermediates
      in the photomutagenesis of nitrosamines is discussed.

PMID- 9544195
TI  - Comparative studies of the mutagenicity of environmental tobacco smoke from
      cigarettes that burn or primarily heat tobacco.
AB  - The mutagenicity of particulate matter concentrated from environmental tobacco
      smoke (ETS) from a prototype cigarette that primarily heats tobacco was compared
      to that of four popular commercially available cigarettes that burn tobacco. ETS
      was generated by six individuals simultaneously smoking 1 cigarette each in a 20
      min time period in a 45 m3 environmental chamber operated in the static mode
      (without ventilation). Respirable suspended particles (RSP) were collected on
      polytetrafluoroethylene (PTFE) filters at a flow rate of 3 LPM for 120 min. Less
      ETS-RSP (86-90%) was emitted by the prototype tobacco-heating cigarette than by
      the tobacco-burning cigarettes. RSP was extracted from the filters by sequential
      sonication in acetone and dichloromethane. The acetone extract was dried under
      nitrogen and the dichloromethane filtrate was added and then dried to obtain ETS
      RSP for testing. Mutagenicity was assessed in the microsuspension modification of
      the Ames Salmonella/microsome assay with strains TA98 and YG1024 in the presence
      of 5% S9 metabolic activation. The results show that the mutagenic activity of
      RSP from the prototype cigarette was reduced by 75-83% on a per-mg basis when
      compared to the commercially available cigarettes and was reduced by 96-98% when
      calculated as revertants/m3 air under identical smoking conditions.

PMID- 9544196
TI  - High production of nondisjunction mutants in the offspring of Drosophila
      melanogaster females exposed to carbon dioxide at meiosis I.
AB  - Drosophila melanogaster females homozygous for X-linked recessive markers, y and
      wi, were exposed to CO2 and mated with y+ w+/Y males. The progeny were sampled
      and inspected for y wi/y wi/Y (XXY) and y+ w+/O (XO) mutants. The frequency of
      nondisjunction XXY mutants after a 90-min exposure to CO2 increased 100-fold
      above the control level in the first-day brood but did not increase above the
      control level in the second to sixth broods, showing that CO2 is an extremely
      potent inducer of nondisjunction in mature oocytes during meiotic metaphase I but
      is not harmful to immature oocytes. Nondisjunction-causing damage induced by CO2
      in mature oocytes disappeared completely within one day after CO2 treatment, as
      evidenced by a reduction of the number of XXY mutants to the control level when
      the mating of CO2-treated females was delayed by one day. CO2-induced
      nondisjunction is probably due to damage to spindle microtubules in mature
      oocytes at metaphase I. N2 is a less potent inducer of nondisjunction than CO2.
      Maternal X-irradiation with 4 Gy did not induce XXY mutants, showing that medium
      level radiation does not induce nondisjunction. The results support Gaulden's
      hypothesis that oxygen deficits and CO2 increases in the microenvironment of
      mature oocytes can be potent inducers of nondisjunction. The possible
      relationship to the cluster of Down syndrome seen in Berlin shortly after the
      Chernobyl accident is discussed.

PMID- 9544197
TI  - Genotoxic effects of heavy metals: comparative investigation with plant
      bioassays.
AB  - The potential use of micronucleus assays in plants for the detection of genotoxic
      effects of heavy-metal ions was investigated. Three different plant systems were
      comparatively investigated in micronucleus tests with Tradescantia pollen mother
      cells (Trad MCN) and micronucleus tests with meristematic root tip cells of
      Allium cepa and Vicia faba (Allium/ Vicia MCN). As3+, Pb2+, Cd2+, Zn2+ caused a
      dose-dependent increase of MCN frequencies in all three test systems. Cu2+ gave
      consistently negative responses in all three tests; Zn2+ caused only a moderate,
      statistically not significant increase of MCN frequencies in Vicia. The ranking
      of genotoxic potencies in all three tests was in the descending order: As3+ >
      Pb2+ > Cd2+ > Zn2+ Cu2+. In experiments with Tradescantia, induction of MCN was
      observed in a concentration range between 1 and 10 mM, whereas in tests with root
      tip cells, higher concentrations (10-1,000 mM) were required to show significant
      effects. Further increase of the exposure levels caused toxic effects (reduction
      of root growth), cell division delays, and a decrease of MCN frequencies.
      Comparisons by linear regression analyses indicated that the sensitivity of the
      three bioassays for heavy metals decreases in the order: Trad MCN > Vicia root
      MCN > Allium root MCN. In further experimental series, a soil sample which
      contained high concentrations of the five metals and a control soil were
      investigated. Aqueous soil extracts induced only weak effects in Trad MCN tests
      and no effects in the root tip assays, whereas cultivation of the plants in the
      soils resulted in a pronounced induction of MCN in the Tradescantia system and
      moderate effects in Vicia and Allium. In conclusion, the results of the study
      indicate that the Trad MCN assay detects the genotoxic effects of heavy metals
      and can be used for biomonitoring metal-contaminated soils.

PMID- 9544198
TI  - Transgenic model systems, National Institute of Environmental Health Sciences,
      Research Triangle Park, North Carolina, March 17 and 18, 1997.

PMID- 9544199
TI  - Physicochemical high throughput screening: parallel artificial membrane
      permeation assay in the description of passive absorption processes.

PMID- 9544200
TI  - Design of novel, potent, noncovalent inhibitors of thrombin with nonbasic P-1
      substructures: rapid structure-activity studies by solid-phase synthesis.
AB  - Study of surface representations of the inhibitor-bound thrombin P-1 pocket
      revealed a lipophilic recess in this pocket which is not occupied by any known
      inhibitor. Solid-phase synthesis was used to generate benzylamides of D
      diphenylAlaPro by aminolysis of Boc dipeptide Kaiser resin. The resulting amides
      inhibited thrombin in the range IC50 = 3-13,000 nM, and the structure-activity
      relationships and molecular modeling suggest a unique fit of the benzyl side
      chain into P-1 with the meta substituent occupying the recess.

PMID- 9544201
TI  - Cytotoxic activities of Mannich bases of chalcones and related compounds.
AB  - Various Mannich bases of chalcones and related compounds displayed significant
      cytotoxicity toward murine P388 and L1210 leukemia cells as well as a number of
      human tumor cell lines. The most promising lead molecule was 21 that had the
      highest activity toward L1210 and human tumor cells. In addition, 21 exerted
      preferential toxicity to human tumor lines compared to transformed human T
      lymphocytes. Other compounds of interest were 38, with a huge differential in
      cytotoxicity between P388 and L1210 cells, and 42, with a high therapeutic index
      when cytotoxicity to P388 cells and Molt 4/C8 T-lymphocytes were compared. In
      general, the Mannich bases were more cytotoxic than the corresponding chalcones
      toward L1210 but not P388 cells. A ClusCor analysis of the data obtained from the
      in vitro human tumor screen revealed that the mode of action of certain groups of
      compounds was similar. For some groups of compounds, cytotoxicity was correlated
      with the sigma, pi, or molar refractivity constants in the aryl ring attached to
      the olefinic group. In addition, the IC50 values in all three screens correlated
      with the redox potentials of a number of Mannich bases. X-ray crystallography and
      molecular modeling of representative compounds revealed various structural
      features which were considered to contribute to cytotoxicity. While a
      representative compound 15 was stable and unreactive toward glutathione (GSH) in
      buffer, the Mannich bases 15, 18, and 21 reacted with GSH in the presence of the
      pi isozyme of glutathione S-transferase, suggesting that thiol alkylation may be
      one mechanism by which cytotoxicity was exerted in vitro. Representative
      compounds were shown to be nonmutagenic in an intrachromosomal recombination
      assay in yeast, devoid of antimicrobial properties and possessing anticonvulsant
      and neurotoxic properties. Thus Mannich bases of chalcones represent a new group
      of cytotoxic agents of which 21 in particular serves as an useful prototypic
      molecule.

PMID- 9544202
TI  - Thiol-induced nitric oxide release from 3-halogeno-3,4-dihydrodiazete 1,2
      dioxides.
AB  - In this work we studied the mechanism of nitric oxide (NO) release underlying the
      vasorelaxant and antiaggregant effect of 3,4-dihydrodiazete 1,2-dioxides (DD).
      Six derivatives were included in the investigations, namely, 3-bromo- and 3
      chloro-3,4,4-trimethyl-DD (1a,b), 3-bromo- and 3-chloro-4-methyl-3,4
      hexamethylene-DD (2a,b), 3,3,4,4-tetramethyl-DD (3), and 3-methyl-3,4
      hexamethylene-DD (4), and their reactivity toward thiols was analyzed. The 3
      bromo- and 3-chloro-DD derivatives were found to react with thiols; this reaction
      can lead to NO formation, DD 2a being the most reactive compound. 2
      (Hydroxyamino)-2-methylbutan-3-one oxime (5a) and 2-hydroxy-2-methylbutan-3-one
      oxime (6) were the main products isolated from the reaction of 1a with cysteine.
      Reaction rates of DD with thiols were dependent upon pH and concentration of the
      reagents. Maximum rates of NO release corresponded to thiol concentrations in the
      range of 1 mM. Consistent with reaction kinetics data and products isolated, a
      reaction mechanism was proposed. Addition of 2a to bovine aortic endothelial
      cells led to strong NO release indicating a reaction with endogenous thiols. In
      rat mesenterial arteries, the vasorelaxant action of 2a was only slightly
      influenced by addition of thiol to the incubation medium. For the most reactive
      DD derivatives, cytotoxic effects were observed at concentrations roughly 2
      orders of magnitude higher than those inducing vasorelaxation.

PMID- 9544203
TI  - Design and synthesis of enantiomers of 3,5-dinitro-o-tyrosine: alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropanoic acid (AMPA) receptor antagonists.
AB  - The R- and S-isomers of 3,5-dinitro-o-tyrosine (6a,b) have been synthesized
      through the use of chemoenzymatic synthesis and shown to bind differentially with
      the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid (AMPA, 3) receptors.
      The phenolic functional group of these o-tyrosine analogues was designed to act
      as a bioisostere of the gamma-carboxyl group of glutamate. The S-isomer of 3,5
      dinitro-o-tyrosine (6b) was 6.5 times more potent than the R-isomer (6a) in
      inhibiting [3H]AMPA binding with IC50 values of 13 +/- 7 and 84 +/- 26 microM,
      respectively. The phenolic group was important for binding affinity since the
      methoxy compound 7 was less potent than the phenolic compound 6 in inhibiting the
      binding of AMPA. The free amino group was also shown to be important since the N
      acetyl analogue 15 and the N-t-BOC compounds 16 and 17 exhibited very low
      affinity for the AMPA receptors. AMPA receptor functional tests showed that the o
      tyrosine analogues are antagonists and that the S-isomer 6b (IC50 = 630 +/- 140
      microM) was more potent than the racemate 6 (IC50 = 730 +/- 88 microM) while the
      R-isomer 6a was inactive up to 1 mM concentration, which is consistent with the S
      isomer having higher binding affinity than the R-isomer.

PMID- 9544204
TI  - Novel nonpeptide CCK-B antagonists: design and development of quinazolinone
      derivatives as potent, selective, and orally active CCK-B antagonists.
AB  - We have designed a novel series of CCK-B receptor antagonists by combining key
      pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two
      known series. Our earlier studies showed that compounds with methylene linkers in
      our "target" produced moderate binding affinity and selectivity for CCK-B
      receptors, whereas its higher and lower homologues resulted in loss of affinity.
      Introduction of -NH- as a linker dramatically enhanced binding affinity and
      selectivity for CCK-B receptors, thus providing several compounds with single
      digit nanomolar binding affinity and excellent selectivity. Analogous to the
      earlier studies of the series of quinazolinone derivatives 3, we also found 3
      isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron
      withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B
      potency. Representative compounds of this series were tested in the functional
      assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active
      in the elevated rat X-maze test. These compounds were also evaluated for their
      pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22%
      in rats.

PMID- 9544205
TI  - Inhibition of Fc epsilon RI-mediated activation of mast cells by 2,3,4
      trihydropyrimidino[2,1-a]isoquinolines.
AB  - Assays based on reporter gene technology represent today an important tool in the
      pharmaceutical industry for discovering novel compound classes interfering with
      the activation and signaling of target cells after stimulation. Here we describe
      a reporter gene assay targeting mast cell activation of IgE plus antigen,
      established in an attempt to identify substances preventing type I allergy
      (allergic rhinitis, allergic conjunctivitis, allergic asthma, and acute and
      chronic urticaria). The assay is based on a murine mast cell line designated
      CPII, stimulation by IgE plus antigen, and a reporter gene construct with the TNF
      alpha promoter linked to luciferase as a read-out system. Via screening about
      50,000 substances, compound 2 was found to inhibit the reporter gene induction in
      the submicromolar range in this assay. Analogues of compound 2 of the 2,3,4
      trihydropyrimidino[2,1-a]isoquinoline type were synthesized starting from 2-alkyl
      substituted benzonitriles via aminolysis with 1,3-diaminopropane, dimetalation of
      2-substituted 2-phenyl-1,4,5,6-tetrahydropyrimidines with n- and sec-butylithium,
      reaction with carboxylic acid methyl esters, and finally acidic dehydration. From
      about 50 derivatives, compound 41 was selected as a lead structure with an IC50
      of 0.2 microM and a TC50 of 2.7 microM. In a first profiling in secondary assays,
      it effectively interfered with the production of mediators such as TNF alpha, IL
      4, IL-6, IL-13, and leukotriene synthesis as measured by the corresponding
      ELISAs. In addition, a passive cutaneous anaphylaxis in mice (a typical type I
      reaction) is inhibited to more than 90% by compound 41, when administered
      intradermally 90 min before challenge.

PMID- 9544206
TI  - 2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease.
AB  - A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated
      as inhibitors of the complement enzyme C1r. C1r is a serine protease at the
      beginning of the complement cascade, and complement activation by beta-amyloid
      may represent a major contributing pathway to the neuropathology of Alzheimer's
      disease. Compounds such as 7-chloro-2-[(2-iodophenyl)-amino]benz[d][1,3]oxazin-4
      one (32) and 7-methyl-2-[(2-iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show
      improved potency compared to the reference compound FUT-175. Many of these active
      compounds also possess increased selectivity for C1r compared to trypsin and
      enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4
      one (1).

PMID- 9544207
TI  - Steroidal and nonsteroidal sulfamates as potent inhibitors of steroid sulfatase.
AB  - Synthetic routes to potent steroidal and nonsteroidal sulfamate-based active site
      directed inhibitors of the enzyme steroid sulfatase, a topical target in the
      treatment of postmenopausal women with hormone-dependent breast cancer, are
      described. Novel compounds were examined for estrone sulfatase (E1-STS)
      inhibition in intact MCF-7 breast cancer cells and placental microsomes. Reaction
      of the sodium salt of estrone with sulfamoyl chloride gave estrone 3-O-sulfamate
      (EMATE, 2) which inhibits E1-STS activity potently (> 99% at 0.1 microM in intact
      MCF-7 cells, IC50 = 65 pM) in a time- and concentration-dependent manner,
      suggesting that EMATE is an active site-directed inhibitor. EMATE is also active
      in vivo orally. 5,6,7,8-Tetrahydronaphthalene 2-O-sulfamate (7) and its N
      methylated derivatives (8 and 9) were synthesized, and 7 inhibits the E1-STS
      activity in intact MCF-7 cells by 79% at 10 microM. 4-Methylcoumarin 7-O
      sulfamate (COUMATE) and its derivatives (14, 16, and 18) were prepared to extend
      this series of nonsteroidal inhibitors, and COUMATE reduces the E1-STS activity
      in placental microsomes by > 90% at 10 microM. Although the orally active COUMATE
      is less potent than EMATE as an active site-directed inhibitor, it has the
      important advantage of being nonestrogenic. Analogues (20, 22, 24, 26, 27, 31,
      33, 39, and 44) of COUMATE were synthesized to study its structure-activity
      relationships, and sulfamates of tetralones (46 and 48) and indanones (49, 51,
      and 53) were also prepared. While most of these compounds were found to inhibit
      E1-STS activity less effectively than COUMATE, one analogue, 3,4-dimethylcoumarin
      3-O-sulfamate (24), was found to be some 12-fold more potent than COUMATE as an
      E1-STS inhibitor in intact MCF-7 cells (IC50 = 30 nM for 24, cf. 380 nM for
      COUMATE). Hence, highly potent sulfamate-based inhibitors of steroid sulfatase,
      such as EMATE, COUMATE, and 24, possess therapeutic potential and will allow the
      importance of estrogen formation in breast tumors via the E1-STS pathway to be
      assessed. A pharmacophore for active site-directed sulfatase inhibition is
      proposed.

PMID- 9544208
TI  - Novel 5-(3-aryl-2-propynyl)-5-(arylsulfonyl)thiazolidine-2,4-diones as
      antihyperglycemic agents.
AB  - Novel 5-(3-aryl-2-propynyl)-5-(arylsulfonyl)thiazolidine-2,4-diones and 5-(3-aryl
      2-propynyl)-5-(arylsulfanyl)thiazolidine-2,4-diones were prepared and evaluated
      as oral antihyperglycemic agents in the obese, insulin resistant db/db mouse
      model at 100 mg/kg and, if the analogue had sufficient potency, 20 mg/kg. The
      sulfonylthiazolidinediones, 2, were more potent than the corresponding
      sulfanylthiazolidinedione congeners, 1. With regard to substituent effects on the
      3-propynyl phenyl ring (Ar') of 2, 4-halogen substitution generally resulted in
      the more potent analogues. Substituent effects on the phenylsulfonyl moiety (Ar)
      of 2 were less clear, although para-halogen substitution on Ar generally was
      preferable. 2-Pyridinesulfonyl derivatives (Ar = 2-pyridine in 2) also had good
      potency. Several compounds from series 2 were effective at lowering glucose and
      insulin in the obese, insulin resistant ob/ob mouse at the 50 mg/kg oral dose.
      Compound 20 significantly improved the glucose tolerance of obese, insulin
      resistant Zucker rats at the 20 mg/kg dose level and had no effect on plasma
      glucose or on glucose tolerance in normal rats fasted for 18 h at the 100 mg/kg
      level.

PMID- 9544209
TI  - Synthesis and endectocidal activity of novel 1-(arylsulfonyl)-1
      [(trifluoromethyl)sulfonyl]methane derivatives.
AB  - We have recently synthesized a series of novel disulfonylmethane compounds that
      have shown anthelmintic and insecticidal (endectocidal) activity. Several
      analogues have shown activity against the internal nematode Haemonchus contortus.
      In sheep studies, these analogues have shown 100% control of this internal
      parasite at a 10 mg/kg rate. In vitro activity against the biting flies, Stomoxys
      calcitrans and Haematobia irritans, has been observed at rates as low as 25 and
      2.3 ppm, respectively. Only marginal activity against the liver fluke Fasciola
      hepatica and Trichostrongylus colubriformis was seen. Respiratory control index
      values on rat liver mitochondria for this series suggested uncoupling of
      oxidative phosphorylation as a mechanism of action. Compound 1 is considered to
      be a promising agent for treatment of parasitized sheep.

PMID- 9544210
TI  - Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6
      bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane
      (TBC1269).
AB  - Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x)
      (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously
      reported biphenyl-based inhibitors that would provide additional interactions
      with the protein. These compounds were assayed for the ability to inhibit the
      binding of sialyl Lewis(x) (sLe(x), 2) bearing HL-60 cells to E-, P-, and L
      selectin fusion proteins. We report that dimeric or trimeric compounds containing
      multiple components of simple nonoligosaccharide selectin antagonists inhibit
      sLe(x)-dependent binding with significantly enhanced potency over the monomeric
      compound. The enhanced potency is consistent with additional binding interactions
      within a single selectin lectin domain; however, multivalent interaction with
      multiple lectin domains as a possible alternative cannot be ruled out. Compound
      15e (TBC1269) showed optimal in vitro activity from this class of antagonists and
      is currently under development for use in the treatment of asthma.

PMID- 9544211
TI  - New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3
      dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and
      analgesic agents: discovery and variation of the 5-keto substituent.
AB  - A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans
      (DHDMBFs) were prepared and evaluated as potential nonsteroidal antiinflammatory
      and analgesic agents. Interest in this class of compounds arose when a DHDMBF was
      found to be an active metabolite of the di-tert-butylphenol antiinflammatory
      agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs
      have good in vivo antiinflammatory and analgesic activity after oral
      administration. These compounds inhibit both cyclooxygenase (COX) and 5
      lipoxygenase (5-LOX) in vitro. The cyclooxygenase inhibition was found to be
      selective for the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX
      inhibition may be responsible for the gastrointestinal safety of compounds such
      as 30.

PMID- 9544213
TI  - Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)
      benzothiazolone derivatives.
AB  - A series of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives were
      synthesized and evaluated for anticonvulsant activity. The compounds were
      assayed, intraperitoneally in mice and per os in rats, against seizures induced
      by maximal electroshock (MES) and pentylenetetrazole (scMet). Neurologic deficit
      was evaluated by the rotarod test. The compounds were prepared to determine the
      relationship between the 2(3H)-benzoxazolone and 2(3H)-benzothiazolone
      derivatives' structures and anticonvulsant activity. Several of these compounds
      showed significant anticonvulsant activity. Compounds 43 and 45 were the most
      active of the series against MES-induced seizures with ED50 values of 8.7 and 7.6
      mg/kg, respectively. Compound 45 displayed good protection against MES-induced
      seizures and low toxicity in rats with an oral ED50 of 18.6 mg/kg and a
      protective index (PI = TD50/ED50) of < 26.9. In vitro receptor binding studies
      revealed that compounds 43 and 45 bind to sigma 1 receptors with nanomolar
      affinities.

PMID- 9544212
TI  - New cyclooxygenase-2/5-lipoxygenase inhibitors. 2. 7-tert-butyl-2,3-dihydro-3,3
      dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and
      analgesic agents: variations of the dihydrobenzofuran ring.
AB  - A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans
      (DHDMBFs) were found to be nonsteroidal antiinflammatory and analgesic agents.
      These compounds are inhibitors of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX)
      with selectivity for the COX-2 isoform. A series of analogues were prepared to
      investigate the scope of this lead. Five ketone side chains from active DHDMBFs
      were used to investigate the effects of changes in the DHDMBF "core": the size
      and identity of the heterocycle and the substituent requirements of the
      heterocycle and phenyl ring. Biological testing showed that a variety of
      structural changes can be accommodated, but no structure was clearly superior to
      the DHDMBF structure.

PMID- 9544214
TI  - Potent antagonists of somatostatin: synthesis and biology.
AB  - The search for synthetic analogues of somatostatin (SRIF) which exhibit selective
      affinities for the five known receptor subtypes (sst1-5) has generated a large
      number of potent agonist analogues. Many of these agonists display good subtype
      selectivities and affinities for the subtypes 2, 3, and 5, with very few
      selective for sst1 or sst4. Until the recent report by Bass and co-workers (Mol.
      Pharmacol. 1996, 50, 709-715; erratum, Mol. Pharmacol. 1997, 51, 170), no true
      antagonists had been discovered, let alone any displaying differential receptor
      subtype selectivity. In this present study, we explore the effect of this
      putative L5,D6 antagonist motif on various series of somatostatin agonist
      analogues, both linear and cyclic. It was found that many D5,L6 agonists could be
      converted into competitive antagonists by applying this motif, the most potent of
      which was H-Nal-cyclo[DCys-Pal-DTrp-Lys-Val-Cys]-Nal-NH2 (32). This antagonist
      was selective for hsst2 with an affinity of 75 nM and an IC50 of 15.1 nM against
      SRIF-14 in a rat in vitro antagonist bioassay. Receptor-selective somatostatin
      antagonists should provide valuable tools for characterizing the many important
      physiological functions of this neuropeptide.

PMID- 9544215
TI  - Antitumor agents. 181. Synthesis and biological evaluation of 6,7,2',3',4'
      substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolones as a new class of
      antimitotic antitumor agents.
AB  - A novel series of 6,7,2',3',4'-substituted-1,2,3,4-tetrahydro-2-phenyl- 4
      quinolones were synthesized and evaluated for interactions with tubulin and for
      cytotoxic activity against a panel of human tumor cell lines, including ileocecal
      carcinoma (HCT-8), breast cancer (MCF-7), lung carcinoma (A-549), epidermoid
      carcinoma of the nasopharynx (KB), renal cancer (CAKI-1), and melanoma cancer
      (SKMEL-2). Most compounds (18, 20, 22-27) showed potent cytotoxic and antitubulin
      effects. The most active compounds (23, 26, 27) demonstrated strong cytotoxic
      effects with ED50 values in the nanomolar or subnanomolar range in almost all
      tumor cell lines. Three active racemates (20, 22, 25) were separated into the
      enantiomers, and generally, the optically pure (-)-isomers (20a, 22a, 25a)
      exhibited greater biological activity than the racemates or (+)-isomers.
      Cytotoxicity and antitubulin activity were closely correlated, with the most
      active compounds (23, 26, 27) having effects comparable to those of colchicine,
      podophyllotoxin, and combretastatin A-4.

PMID- 9544216
TI  - Synthesis and evaluation of compounds that facilitate the gastrointestinal
      absorption of heparin.
AB  - A family of novel compounds (delivery agents) that promote the gastrointestinal
      absorption of USP heparin in rats and primates has been discovered. The delivery
      agents in combination with heparin were administered either orally or
      intracolonically in an aqueous propylene glycol solution and caused dramatic
      increases in both plasma heparin concentrations (anti-Factor Xa) and clotting
      times (APTT). Using one of the most effective delivery agents in this series, an
      estimated relative bioavailability of 8% can be achieved following oral
      administration to cynomolgus monkeys. To establish a correlation between the in
      vivo data and an in vitro parameter, immobilized artificial membrane (IAM)
      chromatography was performed. Log relative k' values were correlated to the
      efficiency of oral heparin delivery.

PMID- 9544218
TI  - Role of the C(6)-hydroxy group in bicyclomycin: synthesis, structure, and
      chemical, biochemical, and biological properties.
AB  - Bicyclomycin (1) is a commercial antibiotic whose primary site of action in
      Escherichia coli is the transcription termination factor rho. A recent structure
      activity relationship study of 1 showed that replacing the C(6)-hydroxy group
      with alkoxy and thioalkoxy substituents led to dramatic losses of inhibitory
      activity in rho biochemical assays. The origin for this structural specificity
      has been explored by the synthesis and chemical, biochemical, and biological
      evaluation of C(6)-amino- (13), C(6)-(hydroxylamino)-(14), and C(6)
      mercaptobicyclomycin (15). These compounds, like 1, are capable of entering into
      hydrogen bond donor interactions with rho and are capable of undergoing C(6) ring
      opening to generate alpha, beta-unsaturated carbonyl, imine, or thione systems.
      The chemical reactivity of 13-15 was compared with that of 1. We observed that 1,
      upon treatment with EtSH under moderate and basic conditions, readily underwent
      C(6) hemiaminal bond cleavage followed by conjugate addition to beta-methylene
      alpha-ketoamide 2 to give Michael addition adducts whereas 13-15 reacted by
      initial cleavage of the C(1)-O(2) bond. Biochemical and biological assays of 13
      15 and related analogues demonstrated that the C(6) hydroxy group in 1 was
      essential for activity. We found that replacing the C(6)-hydroxy group in 1 with
      weaker hydrogen bond donors led to low inhibitory activities in the rho-dependent
      ATPase and transcription termination assays. None of the bicyclomycin derivatives
      exhibited antibiotic activity against E. coli W3350 cells at a 32 mg/mL
      concentration. The apparent specificity for the C(6)-hydroxy group in 1 suggests
      that an efficient hydrogen bond donor interaction from the C(6)-hydroxy group to
      rho or the C(6) hemiaminal bond cleavage to 2 or both is necessary for drug
      function.

PMID- 9544217
TI  - (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol: a
      conformationally restricted analogue of the NR2B subtype-selective NMDA
      antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)- 1
      propanol.
AB  - (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP
      101,606, 1) is a recently described antagonist of N-methyl-D-aspartate (NMDA)
      receptors containing the NR2B subunit. In the present study, the optimal
      orientation of compounds of this structural type for their receptor was explored.
      Tethering of the pendent methyl group of 1 to the phenolic aromatic ring via an
      oxygen atom prevents rotation about the central portion of the molecule. Several
      of the new chromanol compounds have high affinity for the racemic [3H]CP-101,606
      binding site on the NMDA receptor and protect against glutamate toxicity in
      cultured hippocampal neurons. The new ring caused a change in the stereochemical
      preference of the receptor-cis (erythro) compounds had better affinity for the
      receptor than the trans isomers. Computational studies suggest that steric
      interactions between the pendent methyl group and the phenol ring in the acyclic
      series determine which structures can best fit the receptor. The chromanol
      analogue, (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1- yl]chroman-4,7-diol
      (12a, CP-283,097), was found to possess potency and selectivity comparable to CP
      101,606. Thus 12a is a new tool to explore the function of the NR2B-containing
      NMDA receptors.

PMID- 9544219
TI  - Pharmacophoric requirements for cannabinoid side chains: multiple bond and C1'
      substituted delta 8-tetrahydrocannabinols.
AB  - Accumulated evidence indicates that within the cannabinoid structure the
      aliphatic side chain plays a pivotal role in determining cannabimimetic activity.
      We describe the synthesis and affinities for the CB1 and CB2 receptors of a
      series of novel delta 8-THC analogues in which the side-chain pharmacophores are
      conformationally more defined than in the parent molecule. No analogue has the
      side-chain pharmacophore in a fully restricted conformation. However, our design
      serves to narrow down the scope of options for conformational requirements at the
      receptor active sites. All the analogues tested showed nanomolar or subnanomolar
      affinities for the receptors; 2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy
      6H- dibenzo[b,d]pyranyl)-2-hexyl-1,3-dithiolane was found to possess very high
      affinity for both cannabinoid receptors (CB1, Ki = 0.32 nM; CB2, Ki = 0.52 nM).

PMID- 9544220
TI  - Simultaneous measurement of nineteen binding constants of peptides to vancomycin
      using affinity capillary electrophoresis-mass spectrometry.
AB  - On-line affinity capillary electrophoresis-electrospray ionization-mass
      spectrometry (ACE-MS) was used for the simultaneous measurement of multiple
      binding constants of an all-D-tetrapeptide library to the model receptor,
      vancomycin. Determination of Kd values for the 19 peptides of the form Fmoc-DXYA
      is demonstrated. The data are compared with the results obtained for individual
      compounds using ACE-UV, and good correlation between the two detection methods is
      shown. Simultaneous determination of multiple Kd values by ACE-MS is achieved in
      one set of experiments, whereas only one Kd value can be obtained by ACE-UV
      during the same time. ACE-MS measures multiple binding constants in solution in a
      fast and reliable manner using femtomole amounts of samples.

PMID- 9544221
TI  - The ultimate gift: mortui vivos docebunt.

PMID- 9544222
TI  - Treatment of children with relapsed soft tissue sarcoma: report of the German
      CESS/CWS REZ 91 trial.
AB  - BACKGROUND: The present study was performed to evaluate the possibilities of
      relapse treatment in patients heavily pretreated for a soft tissue sarcoma.
      PATIENTS AND METHODS: Prospective, multicenter study in 44 soft tissue sarcoma
      (STS) patients with first relapse. Primary diagnosis was embryonal
      rhabdomyosarcoma (RME) in 17 patients, alveolar rhabdomyosarcoma (RMA) in 13,
      primitive neuroectodermal tumor (PNET) in 6, and miscellaneous soft tissue
      sarcomas in 8 patients. Initial chemotherapy consisted of carboplatin/etoposide
      combination (150 mg/m2 each, days 1 to 4) followed by local therapy including
      surgical treatment and, whenever possible, radiotherapy. RESULTS: In 11/17
      patients without primary tumor resection, CR or PR was achieved following the
      initial two cycles of chemotherapy (61%). The probability of event-free survival
      (pEFS) for RME patients was 0.41 +/- 0.12 at 5 years, and 0.25 +/- 0.12 for RMA
      patients. But, in contrast no PNET patient or patient with another soft-tissue
      sarcoma achieved long-term remission. Additional local radiotherapy significantly
      (P = 0.002) improved pEFS (3-year estimates of 0.23 +/- 0.2 vs. 0.1 +/- 0.1 in
      patients without radiotherapy). CONCLUSIONS: In patients with RME, relapse
      treatment employing a carboplatin/etoposide combination may induce a second
      remission in approximately 40% of patients. Surgical excision and additional
      local radiotherapy seem to be essential to maintain a stable remission. In
      patients with RMA or PNET, however, this treatment strategy is of no long-term
      benefit.

PMID- 9544223
TI  - Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis
      in Japan. Japan LCH Study Group.
AB  - BACKGROUND AND PROCEDURE: The etiology of familial hemophagocytic
      lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly,
      pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all
      with affected siblings, in 18 families who were identified during the period 1986
      1995 in Japan. RESULTS: The presence of consanguinity was evident in two families
      (11%). The majority of families lived in western Japan, where the frequency of
      consanguineous marriage is high. The incidence of FHL was significantly higher in
      the western island, Kyushu, than in other areas. The segregation ratio calculated
      for these families was 0.35 by the Weinberg proband method, showing the autosomal
      recessive inheritance of the disease. Since the diagnosis of an FHL patient
      without affected siblings (sporadic case) is quite difficult, we calculated the
      possible number of sporadic cases; approximately 122 patients could be identified
      as sporadic FHL cases during the same period in Japan. Most of the clinical and
      laboratory findings were not distinguishable from those of other types of
      lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules
      in peripheral blood were observed in half of the patients at diagnosis,
      suggesting the clinical importance of this parameter for early diagnosis. Despite
      intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8
      patients who have survived had received bone marrow transplantation (BMT),
      indicating the effectiveness of BMT for this disorder. CONCLUSIONS: The
      distribution of FHL in areas of highly frequent consanguineous marriage and the
      segregation analysis indicated a genetic factor in FHL. The identification of the
      genes for FHL is expected to contribute to a cure for this disorder, and might
      also enable FHL carrier detection and donor selection for BMT.

PMID- 9544224
TI  - Autopsy in children with cancer who die while in terminal care.
AB  - BACKGROUND: The purpose of this study was to find out whether autopsy of children
      with cancer should be recommended after terminal care, or whether in those
      circumstances it could be abandoned. PATIENTS AND METHODS: One hundred pediatric
      patients with cancer treated at the Children's Hospital, University of Helsinki,
      Finland, died during 1987-92. Seventy children died while in organized terminal
      care. The underlying diagnoses were brain tumors (21), other solid tumors (24),
      and leukemias (25). The method was a retrospective analysis of patients' records
      and autopsy reports, in addition to a structured interview of the two parents
      separately. RESULTS: Autopsy was performed in 40 (57%) of these 70 cases. It was
      more often performed on children dying in hospital (69%) than in those dying at
      home (39%). The autopsy rate also varied with the underlying disease: 68% of
      patients with leukemia, 50% of those with solid tumors, and 52% of those with
      brain tumors were autopsied. Autopsy afforded totally new medical information in
      20% of cases, and important additional information in 55%. Nothing unexpected was
      found in 25%. Almost all the parents (94%) who agreed to autopsy felt that it was
      appropriate. Of both mothers and fathers, 50% felt that knowing the findings at
      autopsy was helpful for them, and all the parents except one mother thought that
      the autopsy of their child would at least be helpful to other patients.
      CONCLUSIONS: Autopsy often provides important and even unexpected information in
      those dying after terminal care. The majority of our parents felt that autopsy
      was an acceptable and appropriate practice. We recommend that autopsies should be
      performed, with the parents' consent, even after terminal care.

PMID- 9544226
TI  - Childhood hemangiopericytoma.
AB  - BACKGROUND: Hemangiopericytoma (HPC) is an uncommon tumor of childhood. PROCEDURE
      AND RESULTS: This paper summarizes our experience with 5 children with
      histologically proven HPC treated in a single institution, including 2 cases of
      congenital HPC. This tumor has varying clinical presentations and biological
      behavior. Congenital tumors have a better prognosis. Chemotherapy and
      radiotherapy had little effect on outcome. CONCLUSION: Complete surgical excision
      is the treatment of choice.

PMID- 9544225
TI  - Rhabdomyosarcoma of extrahepatic biliary tree: initial treatment with
      chemotherapy and conservative surgery.
AB  - BACKGROUND: The very low frequency of rhabdomyosarcoma (RMS) of the extrahepatic
      biliary tree has impeded the development of a standardized form of treatment.
      PROCEDURE: Based on the good response of embryonal RMS to chemotherapy, we used a
      multi-drug protocol as the initial treatment of a 3-year-old girl after obtaining
      adequate transparietohepatic biliary drainage. The treatment achieved complete
      remission. Later conservative laparoscopic surgery revealed only residual scar
      tissue. The patient is alive and well 1 year after remission. DISCUSSION AND
      CONCLUSIONS: Management of this difficult tumor using modern less invasive
      techniques for diagnosis and treatment, with the help of preoperative
      chemotherapy, prevented extensive damage to the biliary tree and allowed complete
      recovery.

PMID- 9544227
TI  - Misleading leads. Thallium-201 uptake in rebound thymic hyperplasia.

PMID- 9544228
TI  - Primitive neuroectodermal tumor (PNET)/extraosseous Ewing sarcoma of the kidney.

PMID- 9544229
TI  - Acute basal ganglia necrosis associated with cytarabine therapy.

PMID- 9544230
TI  - Experience treating a patient with Bloom syndrome and acute myelogenous leukemia.

PMID- 9544231
TI  - Chemotherapy for spinal cord astrocytoma.

PMID- 9544232
TI  - The importance of molecular screening of 11q23 abnormalities in childhood acute
      lymphoblastic leukemia: has the t(11;19)(q23;p13) a higher frequency than that
      revealed by conventional cytogenetic techniques?

PMID- 9544233
TI  - Bone marrow biopsy as prognostic indicator in childhood acute lymphoblastic
      leukemia--another opinion.

PMID- 9544234
TI  - The multi-epitope approach for immunotherapy for cancer: identification of
      several CTL epitopes from various tumor-associated antigens expressed on solid
      epithelial tumors.
AB  - One approach to development of specific cancer immunotherapy relies on the
      induction of cytotoxic T lymphocytes (CTL) specific for tumor-associated antigens
      (TAA). Induction of TAA-specific CTL could be used towards the eradication of
      established tumors, or to prevent their dissemination or recurrence after primary
      treatment. The present study identifies a set of CTL epitopes from TAA frequently
      found on solid epithelial tumors such as breast, lung and gastro-intestinal
      tumors. Specifically, HLA-A2.1 binding peptides from the MAGE2, MAGE3, HER-2/neu
      and CEA antigens were tested for their capacity to elicit in vitro anti-tumor CTL
      using lymphocytes from normal volunteers and autologous dendritic cells as
      antigen-presenting cells. A total of 6 new epitopes (MAGE2[10(157)],
      MAGE3[9(112)], CEA[9(691)], CEA[9(24)], HER2[9(435)] and HER2[9(5)]) were
      identified which were capable of specifically recognizing tumor cell lines lines
      expressing HLA-A2.1 and the corresponding TAA. In one case (CEA[9(24)]),
      induction of vigorous anti-tumor CTL responses required epitope engineering to
      increase HLA-A2.1 binding affinity. Finally, most of the newly identified
      epitopes (5 out of 6) were found to be highly crossreactive with other common HLA
      alleles of the A2 supertype (A2.2, A2.3, A2.6 and A6802), thus demonstrating
      their potential in providing broad and non-ethnically biased population coverage.
      The results are discussed in the context of the development of multi-epitope
      based therapies with broad applicability for patients suffering from commonly
      found tumors.

PMID- 9544236
TI  - Age-related defect of phospholipase C activity, differential expression of the
      beta 2 isoform in active T lymphocytes from aged humans.
AB  - The activation of phosphoinositide-specific PLC is one of the early cellular
      responses to various growth factors and mitogens. It is known that these
      functions are altered with ageing. Here we show that the beta 2 isozyme is
      decreased with ageing in a peculiar T lymphocyte subpopulation involved in the
      immune response, namely the active T lymphocytes. The presence and cellular
      distribution of PLC isozymes were investigated with immunochemical and
      immunocytochemical methods. The in situ immunocytochemistry displayed the
      presence of the beta and gamma isoforms in the cytoplasm, while no reactivity for
      the delta isoform was observed regardless of the age. The immunoblot analysis
      showed an increased expression in the beta 2 isoform in the young and an equal
      expression of the gamma 1 isoform in either age group. Our findings suggest that
      the age-related defect of PLC activity is possibly due to an impaired expression
      of isozymes in aged active T lymphocytes.

PMID- 9544235
TI  - HLA-DP: a class II restriction molecule involved in epitope spreading during the
      development of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central
      nervous system. It is widely believed that complex polygenic inheritance patterns
      involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and
      current evidence indicates that disease risk vs disease outcome may be associated
      with distinctly different HLA class II alleles. We have recently shown that the
      early development of MS is accompanied by an extensive plasticity of myelin self
      recognition with the acquisition of neo-autoreactivity, or epitope spreading, as
      a prominent feature. Although we did not observe a common determinant recognized
      by patients sharing identical HLA-DR or -DQ class II alleles, we did observe
      epitope spreading to the p50-63 determinant of myelin proteolipid protein (PLP)
      in two study subjects showing complete disparity at HLA-DR and -DQ but identity
      at the HLA-DP allele DPB1*0301. In the present study we show that self
      recognition during the early stages in the development of MS involves HLA-DP
      class II restricted responses to the PLP 50-63 spreading determinant. Our results
      suggest that self-presentation by HLA-DP may play an important role in epitope
      spreading and in the propagation of self-recognition during the clinical
      progression of MS.

PMID- 9544237
TI  - Kawasaki disease and the T-cell antigen receptor.
AB  - We investigated the evidence for an infectious etiology of Kawasaki disease (KD),
      an acute vasculitis of unknown etiology, by assessing the effects of KD on the T
      cell antigen receptor variable beta region families (V beta). Using 3-color flow
      cytometry, we studied KD patients pre- and post-intravenous gamma globulin (IVIG)
      therapy and at > 40 days post therapy, additionally comparing them to matched
      pediatric control patients (PCC) and their own healthy parents (one parent/KD
      child). Of all the V beta families examined, only V beta 2 exhibited
      statistically significant differences, between the pre- and post-IVIG samples and
      preIVIG and parent samples. No associations were found between V beta 2 findings
      and T cell memory, activation, or adhesion markers. For 2 KD patients, 4 parents,
      and 1 PCC participant, > 15% of resting CD8+ lymphocytes and > 15% of blastic
      CD8+ lymphocytes expressed a single V beta family, which varied by individual,
      without similar expansions in the CD4+ cell populations. One of the participants
      with this abnormality was the only one with significant cardiac abnormalities.
      For all participants with the V beta abnormality, other T-cell abnormalities were
      extensive and involved both CD4+ and CD8+ cells. We suggest that V beta 2 changes
      do occur in KD, as previously reported. However, these may not be involved in
      disease pathogenesis. Other V beta changes also occur. Those occurring in parents
      may reflect asymptomatic reinfection with an infectious agent causing KD.
      Further, some KD patients may have restricted cytotoxic T-cell responses to that
      as yet unidentified agent; this restricted response may be associated with more
      severe cardiac involvement.

PMID- 9544238
TI  - Individuals from multiplex insulin-dependent diabetes mellitus (IDDM) families
      express higher levels of TCRBV2S1 than controls.
AB  - T lymphocytes recognise peptide antigens through the T cell antigen receptor,
      which is composed of variable alpha and beta chains. There are forty-six
      functional variable regions on the beta chain. In this study the expression of
      the T cell receptor beta-chain variable regions 2S1 and 3S1, in a large cohort of
      multiplex insulin-dependent diabetes mellitus families, have been determined by
      use of monoclonal antibodies and flow cytometry. Peripheral blood was collected
      from these multiplex families and three control groups, healthy individuals,
      sporadic insulin-dependent diabetes mellitus patients and non-insulin-dependent
      diabetes mellitus patients. The level of TCRBV2S1 expression in the multiplex
      families was significantly higher than all the control groups for both the CD4+
      and CD8+ T lymphocyte subsets. Detailed analysis of the family data showed that
      this increased expression was not associated with age, sex, HLA type or the
      diabetic phenotype. The TCRBV3S1 expression in all the diabetic cohorts was
      significantly lower than the healthy controls, in the CD4 subset only. Detailed
      analysis of the family data showed only the fathers TCRBV3S1 expression was lower
      than the healthy controls. This study gives further insight into TCRBV usage
      which could reflect the mechanism of the autoimmune response in IDDM multiplex
      families.

PMID- 9544239
TI  - Analysis of HLA class I and class II in Na-Dene and Amerindian populations from
      British Columbia, Canada.
AB  - We analyzed the distribution of HLA class II alleles and haplotypes in one Na
      Dene (Athabaskan) group from British Columbia (Canada) by PCR amplification of
      the DRB1, DQA1 and DQB1 second exon sequences. We extended the typing of the DRB1
      in an Amerindian group (Penutian) from British Columbia. The presence of the
      alleles DRB1* 0405, *0407 and *0410 only in Na-Dene and alleles DRB1*0408,
      *1301*1302, *1304, *1305, *1502 and *1601 only in Amerindians suggests separate
      origins of these two groups. There were fifteen different DRB1/DQA1/DQB1
      haplotypes. One unique haplotype previously reported in Native Americans was
      found. Thirty-four per cent of Athabaskans presented Native American haplotype
      DRB1*1402/DQA1*0501/DQB1*0301. In addition, the results of this study are
      compatible with previous evidence with mitochondrial (mtDNA) polymorphisms
      indicating that Amerindians and Na-Dene populations derived from different
      migrations from Asia.

PMID- 9544240
TI  - MHC haplotype analysis by artificial neural networks.
AB  - Conventional matching is based on numbers of alleles shared between donor and
      recipient. This approach, however, ignores the degree of relationship between
      alleles and haplotypes, and therefore the actual degree of difference. To address
      this problem, we have compared family members using a block matching technique
      which reflects differences in genomic sequences. All parents and siblings had
      been genotyped using conventional MHC typing so that haplotypes could be assigned
      and relatives could be classified as sharing 0, 1 or 2 haplotypes. We trained an
      Artificial Neural Network (ANN) with subjects from 6 families (85 comparisons) to
      distinguish between relatives. Using the outputs of the ANN, we developed a
      score, the Histocompatibility Index (HI), as a measure of the degree of
      difference. Subjects from a further 3 families (106 profile comparisons) were
      tested. The HI score for each comparison was plotted. We show that the HI score
      is trimodal allowing the definition of three populations corresponding to
      approximately 0, 1 or 2 haplotype sharing. The means and standard deviations of
      the three populations were found. As expected, comparisons between family members
      sharing 2 haplotypes resulted in high HI scores with one exception. More
      interestingly, this approach distinguishes between the 1 and 0 haplotype groups,
      with some informative exceptions. This distinction was considered too difficult
      to attempt visually. The approach provides promise in the quantification of
      degrees of histocompatibility.

PMID- 9544241
TI  - Investigation of two yeast genes encoding putative isoenzymes of phosphoglycerate
      mutase.
AB  - Our previous data indicated that GPM1 encodes the only functional
      phosphoglycerate mutase in yeast. However, in the course of the yeast genome
      sequencing project, two homologous sequences, designated GPM2 and GPM3, were
      detected. They have been further investigated in this work. Key residues in the
      deduced amino acid sequence, shown to be involved in catalysis for Gpm1 (i.e.
      His8, Arg59, His181) are conserved in both enzymes. Overexpression of the genes
      under control of their own promoters in a gpm1 deletion mutant did not complement
      for any of the phenotypes. This could in part be attributed to a lack of
      expression due to their weak promoters. Higher level expression under the control
      of the yeast PFK2 promoter partially complemented the gpm1 defects, without
      restoring detectable enzymatic activity. Nevertheless, deletion of either GPM2 or
      GPM3, or the two deletions in concert, did not produce any obvious lesions for
      growth on a variety of different carbon sources, nor did they change the levels
      of key intermediary metabolites. We conclude that both genes evolved from
      duplication events and that they probably constitute non-functional homologues in
      yeast.

PMID- 9544242
TI  - Post-translational fate of CAN1 permease of Saccharomyces cerevisiae.
AB  - To study the post-translational fate of arginine permease (Can1p), the gene
      coding for this transport protein was placed behind a constitutive promoter of
      plasma membrane ATPase (PMA1) and furnished with a Myc tag. In exponential-phase
      cells the amount of Can1p is constant, although turnover can be demonstrated. A
      rapid decrease in transport activity during the early stationary phase is
      paralleled by a corresponding net degradation of the protein. The amount of Can1p
      present in exponential cells grown on various nitrogen sources is the same,
      except in arginine-grown cells, in which the amount of the protein is markedly
      lower. This occurs solely when arginine serves as nitrogen source but not as an
      immediate consequence of, for example, arginine addition to cells growing on
      other nitrogen sources. it was demonstrated that Can1p is phosphorylated. Since
      Can1p expression under the PMA1 promoter is glucose-dependent, the amount of the
      permease expressed in high-glucose-grown cells is higher than in low-glucose
      grown ones. Only a part of the Can1p overexpressed in high-glucose-grown cells is
      phosphorylated, while in low-glucose-grown cells the phosphorylated form probably
      represents the majority of Can1p. The permease phosphorylation or
      dephosphorylation is not related to transinhibition.

PMID- 9544243
TI  - The Saccharomyces cerevisiae TGL2 gene encodes a protein with lipolytic activity
      and can complement an Escherichia coli diacylglycerol kinase disruptant.
AB  - Escherichia coli cells with a disrupted diacylglycerol kinase gene are unable to
      grow on media containing arbutin due to a lethal accumulation of diacylglycerol.
      In order to isolate genes from the yeast Saccharomyces cerevisiae involved in
      diacylglycerol metabolism we complemented an E. coli diacylglycerol kinase
      disruptant with a yeast genomic library and transformants were selected capable
      of growing in the presence of arbutin. Using this method, a gene (TGL2) was
      isolated coding for a protein resembling lipases from Pseudomonas. After
      expression of the TGL2 gene in E. coli, lipolytic activity towards
      triacylglycerols and diacylglycerols with short-chain fatty acids could be
      measured. Therefore, it is very likely that the TGL2 gene can complement the E.
      coli diacylglycerol kinase disruptant, because it encodes a protein that degrades
      the diacylglycerol accumulated after growth in the presence of arbutin.
      Disruption of the TGL2 gene in S. cerevisiae did not result in a detectable
      phenotype. The role of the Tgl2 protein in lipid degradation in yeast is still
      unclear.

PMID- 9544244
TI  - Isolation and characteristics of yeasts able to grow at low concentrations of
      nutrients.
AB  - Seven oligotrophic yeasts, which can grow in a 10(4)-fold dilution of malt-yeast
      glucose-peptone medium (10(-4) YM), were mainly isolated from soil. These yeasts
      belong to the Cryptococcaceae. When inoculated at about 10(2) cells/ml in 10(-4)
      YM, the isolates grew to 1.4 x 10(3)-2.4 x 10(5) cells/ml after 3 days. Some
      culture collection yeasts fell into three groups according to their growth
      characteristics in 10(-4) YM, one group showing characteristics of the
      oligotrophic yeasts. The half-saturation values of uptake by the five isolated
      oligotrophic yeasts for D-glucose, L-leucine and L-amino acids were 6.0-25.0, 1.7
      43.3 and 3.5-21.6 microM, respectively. The oligotrophic yeasts suspended in 10
      mM-phosphate buffer (pH 6.0) had high tolerances for starvation, and remained
      more than 15% viable after 90 days of starvation.

PMID- 9544245
TI  - Identification and kinetic analysis of a functional homolog of elongation factor
      3, YEF3 in Saccharomyces cerevisiae.
AB  - Yeast and other fungi contain a soluble elongation factor 3 (EF-3) which is
      required for growth and protein synthesis. EF-3 contains two ABC cassettes, and
      binds and hydrolyses ATP. We identified a homolog of the YEF3 gene in the
      Saccharomyces cerevisiae genome database. This gene, designated YEF3B, is 84%
      identical in protein sequence to YEF3, which we will now refer to as YEF3A. YEF3B
      is not expressed during growth under laboratory conditions, and thus cannot
      rescue growth of YEF3A deletion strains. However, YEF3B can take the place of
      YEF3A in vivo when expressed from the YEF3A or ADH1 promoters. The products of
      the YEF3A and YEF3B genes, EF-3A and EF-3B, respectively, were expressed from the
      ADH1 promoter and purified. Both factors possessed basal and ribosomal-stimulated
      ATPase activity, and had similar affinity for yeast ribosomes (103 to 113 nM).
      K(m) values for ATP were similar, but the Kcat values differed significantly.
      Ribosome-dependent ATPase activity of EF-3A was more efficient than EF-3B, since
      the Kcat and Kcat/K(m) values for EF-3A were about two-fold higher; however, the
      difference in Kcat/K(m) values between the two factors was small for basal ATPase
      activity.

PMID- 9544246
TI  - Generation of Saccharomyces cerevisiae deletants and basic phenotypic analysis of
      eight novel genes from the left arm of chromosome XIV.
AB  - The disruption of eight novel genes was realized in two genetic backgrounds.
      Among these open reading frames, NO333, NO348 and NO364 presented homologies with
      other proteins of yeast or other organisms, whereas NO320, NO325, NO339, NO384
      and NO388 showed no similarity with any protein. Tetrad analysis of heterozygous
      deletant strains revealed that NO348, NO364 and NO388 are essential genes for
      vegetative growth, whereas NO320, NO325, NO333, NO339 and NO384 are non
      essential. Basic phenotypic analyses of the non-lethal deletant strains as
      suggested in the six-pack B0 programme did not reveal any significant differences
      between parental and mutant strains.

PMID- 9544247
TI  - Cloning, sequencing and disruption of the ARG8 gene encoding acetylornithine
      aminotransferase in the petite-negative yeast Kluyveromyces lactis.
AB  - A recombinant plasmid was isolated from a Kluyveromyces lactis genomic DNA
      library which complements a Saccharomyces cerevisiae arg8 mutant defective in the
      gene encoding acetylornithine aminotransferase. The complementation activity was
      found to reside within a 2.0 kb DNA fragment. Nucleotide sequence analysis
      revealed an open reading frame able to encode a 423-residue protein sharing 68.1%
      and 35.0% sequence identities with the products of the ARG8 and argD genes of S.
      cerevisiae and Escherichia coli. That the cloned gene, KlARG8, is the functional
      equivalent of S. cerevisiae ARG8 was supported by a gene disruption experiment
      which showed that K. lactis strains carrying a deleted chromosomal copy of KlARG8
      are auxotrophic for arginine.

PMID- 9544248
TI  - The SPL1 tRNA splicing gene of Candida maltosa and Candida albicans.

PMID- 9544249
TI  - Current awareness on yeast.

PMID- 9544250
TI  - Hexose recognition by the pancreatic beta-cell and the gustatory cell.

PMID- 9544251
TI  - Glucose-induced time-dependent potentiation and "run down" of insulin secretion
      in islets of young rats.
AB  - A "run down" phenomenon in isolated islets from young rats has been detected, in
      which the amount of insulin released in response to glucose decreases with time.
      This has been studied in conjunction with glucose-induced time-dependent
      potentiation (TDP) to see if the two are related. Islets, isolated from 7-day-old
      rats, exposed to 16.7 mM glucose for the first time after 30, 75 and 120 minutes
      of perifusion in Krebs-Ringer bicarbonate buffer (KRB) and 2.8 mM glucose, showed
      a progressive loss of responsiveness, and less insulin was released at the later
      times. This run down of the responses was prevented by successive challenges with
      16.7 mM glucose and marked TDP was observed. The earlier the islets were exposed
      to glucose the more effectively was the run down prevented. Also, and perhaps
      causally related to the prevention of run down, the earlier the exposure to
      glucose the greater the TDP of a subsequent response. The results could possibly
      be explained in terms of a shift in metabolism in the isolated 7-day islets, with
      resultant diminution of the signals for the stimulation of insulin release and
      TDP. Early, and repeated exposure to high glucose would appear to minimize and
      delay the metabolic shift.

PMID- 9544252
TI  - ATP-sensitive K+ channel closure is not an obligatory step for glucose-induced
      priming of pancreatic B-cell.

PMID- 9544254
TI  - Modulation of three types of potassium selective channels by NAD and other
      pyridine nucleotides in human pancreatic beta-cells. NAD and K+ channels in human
      beta-cells.

PMID- 9544253
TI  - Bursting electrical activity generated in the presence of KATP channel blockers.
      Pharmacology, sensitivity to intracellular pH and modulation by glucose
      metabolism.

PMID- 9544255
TI  - Novel actions of the potassium channel modulator SDZ PCO 400 on ATP-regulated
      potassium channels in insulin secreting cells. SDZ PCO 400 and beta-cells.

PMID- 9544256
TI  - Effects of protein phosphorylation on the sulphonylurea receptor of the
      pancreatic beta-cell.

PMID- 9544257
TI  - Intracellular second messengers.

PMID- 9544258
TI  - Immunological analysis of G-protein expression in the endocrine pancreas.

PMID- 9544259
TI  - Calcyclin, a calcium-binding protein, which regulates insulin secretion from the
      permeabilized pancreatic beta-cell.

PMID- 9544260
TI  - Molecular cloning of the cDNA encoding beta-cell calcium/calmodulin-dependent
      protein kinase II.

PMID- 9544261
TI  - Trans-acting factor(s) confer glucose-responsive transcriptional regulation in
      the insulin gene.

PMID- 9544262
TI  - Extracellular messages for pancreatic B-cells.

PMID- 9544263
TI  - The human glucagon-like peptide-1 (GLP-1) receptor. Cloning and functional
      expression.

PMID- 9544264
TI  - Islet release of ACTH-like peptides and their modulatory effect on insulin
      secretion.

PMID- 9544265
TI  - Chronic sympathetic innervation of islets in transgenic mice results in
      differential desensitization of alpha-adrenergic inhibition of insulin secretion.
AB  - The effects of chronic sympathetic hyperinnervation on pancreatic beta-cell
      insulin secretion were investigated utilizing the in vitro perfused pancreas from
      transgenic mice. These mice exhibit islet hyperinnervation of sympathetic neurons
      resulting from overexpression of nerve growth factor in their beta-cells (1). The
      goal was to determine whether sympathetic hyperinnervation increased classic
      alpha-adrenergic inhibition of beta-cell insulin secretion or, in contrast, down
      regulated beta-cell sensitivity to adrenergic input resulting in enhanced insulin
      secretion. Both fasting and fed blood sugars and pancreatic insulin content were
      normal in the transgenics. Response of the transgenic perfused pancreas to low
      glucose (7 mM) was primarily first phase and normal whereas high glucose (22 mM)
      caused enhanced, rather than reduced, insulin secretion of both first and second
      phases. The alpha-antagonist, phentolamine, caused a six-fold increase in glucose
      stimulated insulin secretion from the control pancreas, an effect that was
      blunted for the transgenic pancreas. A similarly blunted response to phentolamine
      occurred when this agent was superimposed on a combined glucose-forskolin
      stimulus. (The positive effect on insulin secretion by phentolamine in normal
      beta-cell preparations has arguably been ascribed to non-specific ionic effects.)
      Therefore, as a test of possible changes in the ATP regulated K+ channel or the
      linked Ca++ channels, glyburide was perfused during glucose stimulation. Insulin
      secretion in response to glyburide was increased two fold in the control
      pancreas. However, with the transgenic pancreas, in contrast to the enhanced
      response to glucose, the effect of glyburide was almost completely inhibited. It
      is concluded that: 1) chronic adrenergic hyperinnervation results in enhanced
      glucose-stimulated insulin secretion by desensitization of a major alpha
      adrenergic inhibitory site(s); and 2) adrenergic hyperinnervation acts directly
      or indirectly on ion flux to partially inhibit insulin release, an effect which
      is not desensitized. Since down-regulation of a single alpha-adrenergic receptor
      would be expected to desensitize both phenomena the observed differential
      desensitization indicates that different post receptor events or more than one
      adrenergic receptor are involved.

PMID- 9544266
TI  - Colocalization of WE-14 immunostaining with the classical islet hormones in the
      porcine pancreas.

PMID- 9544267
TI  - Pyridothiadiazines as potent inhibitors of glucose-induced insulin release.

PMID- 9544268
TI  - Increase in [Ca2+]i and subsequent insulin release from beta TC3-cells with the L
      type Ca(2+)-channel activator, FPL 64176.

PMID- 9544269
TI  - Identification and characterization of non-adrenergic binding sites in insulin
      secreting cells with the imidazoline RX821002.

PMID- 9544270
TI  - PACAP as low as 10(-13) M raises cytosolic Ca2+ activity in pancreatic B-cells by
      augmenting Ca2+ influx through L-type Ca2+ channels to trigger insulin release.

PMID- 9544271
TI  - Characterization of purinergic receptor-evoked increases in intracellular Ca2+
      transients in isolated human and rodent insulin-secreting cells. Purinergic
      receptor signalling and [Ca2+]i in human beta-cells.

PMID- 9544272
TI  - Reciprocal links between metabolic and ionic events in islet cells. Their
      relevance to the rhythmics of insulin release.

PMID- 9544274
TI  - Oscillations of cytosolic Ca2+ in pancreatic islets of Langerhans.

PMID- 9544275
TI  - Effects of localized pulses of high K+ and carbachol on [Ca2+]i in pancreatic
      islets of Langerhans.

PMID- 9544273
TI  - Glyceraldehyde and the pancreatic beta-cell.

PMID- 9544276
TI  - Cyclic AMP, a mediator of GLP-1, acts in concert with glucose and tolbutamide to
      increase cytosolic Ca2+ in pancreatic B-cells.

PMID- 9544277
TI  - Metabolism of phosphatidylcholine in mouse pancreatic islets.

PMID- 9544278
TI  - Phe-Met-Arg-Phe-NH2 (FMRFa)-related peptides inhibit Na/Ca exchange in pancreatic
      B cells.

PMID- 9544279
TI  - Cell culture conditions influence glucose-induced [Ca2+]i responses in isolated
      rat pancreatic B cells.

PMID- 9544280
TI  - Glucose metabolism regulates cytosolic Ca2+ in the pancreatic beta-cell by three
      different mechanisms.

PMID- 9544281
TI  - Heterogeneity of beta-cell secretion. Possible involvement of K-ATP channels.

PMID- 9544282
TI  - Heterogeneity of beta-cell Ca2+ responses to glucose.

PMID- 9544283
TI  - Glucose-induced B-cell recruitment and the expression of hexokinase isoenzymes.

PMID- 9544284
TI  - Physiological behavior of functional subpopulations of single pancreatic beta
      cells.

PMID- 9544285
TI  - Computer modeling of heterogeneous beta-cell populations.

PMID- 9544286
TI  - Reconstructing islet function in vitro.

PMID- 9544287
TI  - New aspects to the functioning and regeneration of pancreatic beta-cells. Cyclic
      ADP-ribose and Reg gene.

PMID- 9544288
TI  - A role for nitric oxide and other inflammatory mediators in cytokine-induced
      pancreatic beta-cell dysfunction and destruction.

PMID- 9544289
TI  - The REG gene and islet cell repair and renewal in type 1 diabetes.

PMID- 9544290
TI  - DNA-damage and NAD(+)-depletion are initial events in oxygen radical induced
      islet cell death.

PMID- 9544291
TI  - Nitric oxide rather than superoxide or peroxynitrite inhibits insulin secretion
      and causes DNA damage in HIT-T15 cells.

PMID- 9544292
TI  - Activation of peritoneal macrophages during the prediabetic phase in low-dose
      streptozotocin-treated mice.

PMID- 9544293
TI  - Immunological reactivity of diabetes-prone BB/OK rats to syngeneic antigens.
      Effect on beta-cell destruction and diabetes onset.

PMID- 9544294
TI  - Effects of oxidants on membrane potential, K+ and Ca2+ currents of mouse
      pancreatic B-cells.

PMID- 9544295
TI  - IAPP and insulin regulation in human pancreatic islets.

PMID- 9544296
TI  - Hyperproinsulinaemia and islet dysfunction in the NIDDM-like syndrome of
      Psammomys obesus.

PMID- 9544297
TI  - Altered secretory responsiveness of BRIN-BD11 cells cultured under hyperglycaemic
      conditions is not readily reversed by subsequent culture in lower glucose
      concentrations.

PMID- 9544298
TI  - B-cell hyperresponsiveness to glucose in NIDDM during prediabetes.

PMID- 9544299
TI  - Insulin treatment prevents adaptation of the endocrine pancreas to pregnancy.

PMID- 9544300
TI  - Islet transplantation.

PMID- 9544301
TI  - The syngeneic islet transplantation to study physiology and pathophysiology of
      pancreatic beta-cells.

PMID- 9544302
TI  - Islet growth after pancreatic fragments autotransplantation into the dog's
      spleen. How can the engrafted islet mass satisfy the demand for its specific
      products?

PMID- 9544303
TI  - The use of immunomagnetic separation for secondary purification of pancreatic
      islets. A comparison of different magnetic fields in the rat.

PMID- 9544304
TI  - Transplantation of syngenic pancreatic islets into rats with streptozotocin
      induced non insulin dependent diabetes mellitus.

PMID- 9544305
TI  - Effects of caffeine on glucose-stimulated insulin release from islet transplants.

PMID- 9544306
TI  - Prevention and treatment of respiratory syncytial virus infections (for advances
      in pediatric infectious diseases).

PMID- 9544307
TI  - Pertussis in older children and adults.

PMID- 9544308
TI  - The athlete: an immunocompromised host.

PMID- 9544309
TI  - Human parvovirus B19 infections in infants and children.

PMID- 9544310
TI  - Controversies in Kawasaki syndrome.

PMID- 9544311
TI  - Neisseria meningitidis in the 1990s.

PMID- 9544312
TI  - Acute and chronic mastoiditis in children.

PMID- 9544313
TI  - Tick-borne diseases.

PMID- 9544314
TI  - Rabies risk and immunoprophylaxis in children.

PMID- 9544315
TI  - Vancomycin resistant enterococci: impact and management in pediatrics.

PMID- 9544316
TI  - Haemophilus influenzae vaccines: 1997.

PMID- 9544317
TI  - Changing poliovirus vaccine policy can be controversial at best.

PMID- 9544318
TI  - New vaccines against mucosal pathogens: rotavirus and respiratory syncytial
      virus.

PMID- 9544319
TI  - Selected topics in novel methods of antibiotic delivery: aerosolized antibiotics
      and lipid preparations.

PMID- 9544320
TI  - Seattle pilot project makes emergency contraception available directly from
      pharmacists.

PMID- 9544321
TI  - Wisconsin health plan rolls out comprehensive pharmacy provider contract.

PMID- 9544322
TI  - First COMT inhibitor approved for Parkinson's disease.

PMID- 9544323
TI  - New warnings issued for bromfenac, astemizole.

PMID- 9544324
TI  - USP moves forward in providing information on botanical products.

PMID- 9544325
TI  - University of Florida signs up Pharm.D. students for Texas, Illinois sites.

PMID- 9544326
TI  - NCPA's TV network primes consumers, pharmacists for pharmaceutical care.

PMID- 9544327
TI  - Assisted suicide: an issue for pharmacists.

PMID- 9544328
TI  - Views on assisted suicide. Perspectives of the AMA and the NHO.

PMID- 9544329
TI  - Views on assisted suicide. The aid-in-dying perspective.

PMID- 9544330
TI  - Views on assisted suicide. An ethicist's perspective.

PMID- 9544331
TI  - Topiramate: a new antiepileptic drug.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug
      interactions, and dosage of topiramate are reviewed. Topiramate is indicated for
      use in the adjunctive treatment of adult partial-onset epilepsy. A sulfamate
      substituted monosaccharide, it is structurally distinct from other antiepileptic
      agents. Topiramate acts by blocking the spread of seizures. Oral topiramate has
      high bioavailability and low protein binding, and as monotherapy its half-life
      permits once- or twice-daily administration. The drug is excreted largely
      unchanged in the urine. Clinical trials have shown that topiramate is effective
      as adjunctive therapy in treating adult partial-onset epilepsy with or without
      secondarily generalized seizures. In adults with refractory partial epilepsy,
      topiramate has shown efficacy when carbamazepine or phenytoin has failed.
      Topiramate may also be effective against partial-onset epilepsy and Lennox
      Gastaut syndrome in children, but more pediatric studies are needed. CNS adverse
      effects are the most common; weight loss and nephrolithiasis have also been
      reported. The drug does not appear to interact significantly with other
      antiepileptic agents, but enzyme inducers like phenytoin and carbamazepine can
      decrease serum topiramate levels by 50%. The initial dosage is 50 mg nightly for
      seven nights, followed by an increase weekly to 400 mg/day in two divided doses.
      Topiramate is more costly than other anticonvulsants; however, drug therapy
      accounts for less than 10% of the total direct cost of epilepsy treatment.
      Topiramate offers an effective, well-tolerated option in patients with adult
      partial-onset seizures.

PMID- 9544332
TI  - Update on childhood immunization.
AB  - Changes made in 1997 and 1998 in the U.S. childhood immunization schedule are
      discussed, with a focus on the use of poliovirus, pertussis, and combination
      vaccines. Oral poliovirus vaccine (OPV), the vaccine of choice for all four doses
      in the polio immunization series since 1962, can cause vaccine-associated
      paralytic poliomyelitis (VAPP). The inactivated poliovirus vaccine (IPV) has not
      been associated with VAPP but must be administered by injection and provides
      inferior intestinal immunity. With the reduced threat of poliovirus importation
      into the United States, the risk of VAPP, although low, has become less
      acceptable. The Centers for Disease Control and Prevention accordingly
      recommended a shift from OPV to IPV in the childhood immunization schedule for
      the United States, effective January 1997. A sequential OPV and IPV series is
      recommended, but the schedule includes an OPV-only option, which may be preferred
      in order to avoid the required injections, and an IPV-only option, which is
      recommended for immunocompromised persons and their contacts. Concern over local
      and systemic reactions associated with whole-cell pertussis vaccines, in addition
      to controversy over a possible relationship between the whole-cell vaccine and
      neurologic damage, has led to the development of new diphtheria and tetanus
      toxoids and acellular pertussis vaccine products for use in the diphtheria and
      tetanus toxoids and pertussis immunization series. Several combination products
      were licensed in 1997, and more are on the way. This will mean fewer inoculations
      for children. Increased use of IPV and acellular pertussis products could reduce
      the frequency of VAPP due to OPV and the local and systemic reactions associated
      with whole-cell pertussis vaccine.

PMID- 9544333
TI  - 0.9% sodium chloride injection with and without heparin for maintaining
      peripheral indwelling intermittent-infusion devices in infants.
AB  - The use of 0.9% sodium chloride injection with and without heparin sodium for
      maintaining peripheral indwelling intermittent-infusion devices (PIIIDs) in
      infants was studied. In this double-blind study, children up to one year of age
      who had a 24-gauge PIIID through which a continuous i.v. infusion was no longer
      running were randomly assigned to have their PIIID capped with 0.9% sodium
      chloride injection with or without heparin sodium 10 units/mL. PIIIDs were capped
      every eight hours if no medications were administered; otherwise, they were
      capped after each dose of an i.v. drug. The heparin group had 26 patients with 28
      evaluable PIIIDs, and the 0.9% sodium chloride injection group had 32 patients
      with 46 evaluable PIIIDs. The two groups did not differ significantly in
      variables assessing the duration of PIIID use, reasons for removal of PIIIDs,
      mean number of cappings, irritant potential of administered drugs, or severity of
      medication-related irritation. There was no significant difference between 0.9%
      sodium chloride injection with and without heparin sodium 10 units/mL in
      maintaining 24-gauge PIIIDs in children younger than one year.

PMID- 9544334
TI  - Stability of acyclovir sodium 1, 7, and 10 mg/mL in 5% dextrose injection and
      0.9% sodium chloride injection.

PMID- 9544335
TI  - Longing for mercy, requesting death: pharmaceutical care and pharmaceutically
      assisted death.

PMID- 9544336
TI  - Legal aspects of expanded prescribing authority for pharmacists.

PMID- 9544337
TI  - Direct-to-consumer advertising: for better profits or for better health?

PMID- 9544338
TI  - Albendazole versus praziquantel for neurocysticercosis.

PMID- 9544339
TI  - Stability of carboplatin in polyvinyl chloride bags.

PMID- 9544340
TI  - Paroxetine treatment of aggression and self-injury in persons with mental
      retardation.
AB  - An open, prospective assessment of the treatment of severe aggression and self
      injurious behavior (SIB) with paroxetine, a serotonin re-uptake inhibitor, in 15
      institutionalized persons with mental retardation was undertaken. Frequency and
      severity of aggression and SIB were charted by trained staff members. Only
      aggression severity was reduced over the entire 4-month follow-up period. Within
      the limits of an open trial, this effect was significant at one month but did not
      remain significant subsequently. The apparent diminution of effectiveness after 4
      weeks of treatment may suggest adaptive changes warranting further study.

PMID- 9544341
TI  - Cognitive representation of motion in individuals with mental retardation.
AB  - Participants with and without mental retardation were compared on their tendency
      to show the representational momentum effect when viewing a stimulus array that
      implied motion. The representational momentum effect occurs when, due to implied
      or apparent motion, an object is more likely to be remembered slightly shifted in
      the direction of motion rather than against the direction of motion. Participants
      with mental retardation showed the representational momentum effect as did
      participants without mental retardation, though the magnitude of the memory shift
      was smaller for participants with mental retardation. Results suggest that
      individuals with mental retardation cognitively process motion information in the
      same general way as do those without mental retardation, although less
      efficiently.

PMID- 9544342
TI  - Assessing perceived agency adherence to the values of community inclusion:
      implications for staff satisfaction.
AB  - Measures of staff members' knowledge (N = 518) of the values of community
      inclusion, perception of agency adherence to community inclusion, and
      satisfaction with relevant components of their jobs were developed. Staff
      represented 130 agencies in a state-wide program of individualized community
      living supports for adults with developmental and/or mental disabilities. Results
      suggest relatively high levels of knowledge about values of inclusion and
      perceived agency adherence to the inclusion philosophy among employees regarding
      the need to provide individuals who have disabilities with opportunities for
      engaging in community daily activities and their rights for services. Employees,
      however, had significantly less knowledge of and noted less agency adherence to
      activities intended to provide consumers with opportunities to make choices.
      Staff who perceived more agency adherence to the philosophy of inclusion were
      more satisfied with their jobs.

PMID- 9544344
TI  - Matching training tasks to abilities of people with mental retardation: a
      learning test versus experienced staff.
AB  - Three sets of predictions were compared concerning the ability of 18 persons with
      severe or moderate mental retardation to learn 12 training tasks. Predictions
      were made by (a) experienced teachers who had worked with the clients for a
      minimum of 8 months and (b) experienced teachers who did not know the clients
      personally but who interacted with them for 30 minutes and by (c) consideration
      of client performance on the Assessment of Basic Learning Abilities test. To
      teach each task to a pass or fail criterion, we applied standard training
      procedures. The Assessment of Basic Learning Abilities test was significantly
      more accurate for predicting client performance than was either group of
      experienced staff. Implications for decreasing the high cost of unproductive
      training time were discussed.

PMID- 9544343
TI  - Evolution of epilepsy in children with mental retardation: five-year experience
      in 78 cases.
AB  - Various aspects of epilepsy, including its evolution, were studied in 78 children
      with mental retardation in a prospective 5-year (1989-1994) follow-up study.
      Level of mental retardation was moderate or even more severe (IQ < 50) in 83% of
      children, and 56% suffered from significant cerebral palsy. Epilepsy remained
      uncontrolled in 28% of cases, 2-year remission was achieved by 26%, and mortality
      was 12% during the study period. Associated cerebral palsy was the most important
      single risk factor for severe epilepsy, and several handicaps seemed to have a
      strong multiplicative effect. Complexity of epilepsy in children with mental
      retardation was reflected by the evolutionary features described.

PMID- 9544345
TI  - Confrontation naming of familiar sounds and pictures by individuals with Down
      syndrome.
AB  - We investigated whether adolescents and young adults with Down syndrome
      experience difficulty in finding words to name familiar objects. In Experiment 1,
      IQ- and MA-matched individuals with Down syndrome and with mental retardation due
      to other causes orally identified familiar pictures and sounds. Results showed no
      evidence of syndrome-specific word-finding difficulty in accuracy or speed.
      Although both groups identified auditory stimuli less accurately and more slowly
      than visual stimuli, results of Experiments 2 and 3 confirmed that young children
      without mental retardation and college students showed the same pattern. Although
      previous researchers have shown expressive speech deficits among people with Down
      syndrome, these results suggest that adolescents and young adults with Down
      syndrome show no syndrome-specific difficulty in finding words to label familiar
      nonverbal sounds or pictures.

PMID- 9544346
TI  - Longitudinal study of institutional downsizing: effects on individuals who remain
      in the institution.
AB  - In a 4-year study we examined the longitudinal effects of deinstitutionalization
      programs on those who remain in institutions being downsized. Individual outcomes
      investigated were community access, social activities, community inclusion,
      family relationships, and choice. Effects of residential relocation on individual
      outcomes such as adaptive behavior were evaluated and total daily per-person
      expenditure on institutional services for participants was determined. Downsizing
      was associated with decreased community integration but no change in most other
      outcomes. Availability of therapy services fell over time, and individuals
      experienced many residential and day program moves within the institution. Per
      person expenditure on services increased substantially. Finally, no significant
      changes in adaptive behavior were associated with intrainstitutional moves.

PMID- 9544347
TI  - Implicit and explicit memory in individuals with mental retardation.
AB  - Students with and without mental retardation from three age groups were compared
      on implicit and explicit memory tasks. Consistent with previous research on
      intelligence-related differences in controlled and automatic processes, students
      without mental retardation performed better than those with mental retardation on
      the explicit memory task, but there was no difference between groups on the
      implicit memory task. For both groups implicit and explicit memory increased from
      age 6 to 8 to age 10 to 12, but did not significantly increase to age 15 to 17.
      Because implicit memory appears to be a relative strength for students with
      mental retardation, we suggest further exploration into broader types of implicit
      processes that may be useful in training situations.

PMID- 9544348
TI  - The health care revolution: a catalyst for professional evolution.

PMID- 9544349
TI  - Test-retest reliability of the evaluation tool of children's handwriting
      manuscript.
AB  - OBJECTIVE: This study examined the test-retest reliability of the legibility
      portion of the Evaluation Tool of Children's Handwriting-Manuscript (ETCH-M).
      METHOD: The sample consisted of 31 first-grade and second-grade students with
      handwriting dysfunction. The ETCH-M was administered two times, 1 week apart, to
      participants. The primary investigator acted as sole rater and followed standard
      scoring procedures. RESULTS: The reliability coefficients were .63 for total
      numeral legibility .77 for total letter legibility, and .71 for total word
      legibility. Individual task reliability coefficients were generally lower and
      ranged from .20 (near-point copy) to .76 (alphabet uppercase). CONCLUSION: Total
      letter, total word, and uppercase letter legibility were more stable than total
      numeral legibility scores and other individual tasks scores. When evaluating
      handwriting for a child, it is important to consider ETCH legibility scores as
      only one aspect of a comprehensive evaluation.

PMID- 9544350
TI  - Clinical interpretation of "test-retest reliability of the Evaluation Tool of
      Children's Handwriting-Manuscript".

PMID- 9544351
TI  - The complexities embedded in family-centered care.
AB  - The recent movement toward family-centered care, which has been propelled by the
      implementation of the Education for All Handicapped Children Amendments of 1986,
      poses considerable challenges to professionals trained in client-centered models
      of service delivery. These challenges are compounded by the fact that our
      understanding of family-centered care lags considerably behind our attempts to
      implement responsive and efficacious services. When practitioners include family
      members more integrally as collaborators in pediatric treatment, their
      perceptions about families and the nature of the therapeutic experience is
      affected. In this article, we present a number of critical dilemmas that are
      based on data drawn from ethnographic research, descriptive studies, and training
      seminars we conducted with pediatric practitioners and parents of children with
      special health care needs. These dilemmas highlight the complexities involved in
      building effective partnerships among all the key players, the influence of
      multiple cultural worlds on everyday practices, and the need to provide supports
      to practitioners for the emotional and social dimensions of practice.
      Implications for practice and future research are presented.

PMID- 9544352
TI  - Estimates of driving abilities and skills in different conditions.
AB  - OBJECTIVES: This research was a preliminary effort to determine whether various
      driving situations seemed to require different driving skills and abilities and
      to identify the relative demands of specific physical, perceptual, cognitive,
      behavioral, and operational skills and abilities in different driving situations.
      METHOD: Experienced driver evaluators and trainers estimated the magnitude of
      driving abilities and skills for different photographed driving situations.
      Pictures of driving scenarios were counterbalanced for road type, traffic
      condition, and weather condition. RESULTS: A multifactorial analysis of variance
      of the total score for each scenario revealed significant main effects for road
      type and traffic condition but not for weather condition. Highway and city
      driving were rated as significantly more demanding overall than residential
      driving, but no difference was found between city and highway driving. Estimates
      of the overall demands for driving in heavy traffic were significantly greater
      than in light traffic. However, driving in inclement weather was not regarded as
      significantly more demanding than driving in sunny weather. Additionally,
      significant interaction effects were found for road type by weather condition and
      traffic by weather condition but not for road type by traffic condition. Through
      multivariate methods to evaluate the significance of individual abilities and
      skills across conditions, significant main and interactive effects were found for
      road type, traffic condition, and weather condition. Post hoc analyses showed the
      impact of these effects on such abilities and skills as scanning, attention and
      concentration, information-processing speed, and others. CONCLUSION: Evaluators'
      quantified estimates of driving demands showed driving as a complex task that (a)
      requires high levels of abilities and skills in all situations; (b) demands
      greater abilities in some situations than in others; and (c) involves different
      kinds and various degrees of abilities and skills, depending on the demand
      characteristics of the situation.

PMID- 9544353
TI  - How occupational therapists teach older patients to use bathing and dressing
      devices in rehabilitation.
AB  - OBJECTIVE: This article describes the methods occupational therapists use to
      teach bathing and dressing device use to older patients in rehabilitation
      programs. The relationship of three patient characteristics to five aspects of
      assistive device instruction was examined. METHOD: The study sample included 86
      patients and 19 occupational therapists who provided the assistive device
      training. Patients were 55 years of age or older and in rehabilitation for an
      orthopedic deficit, cerebrovascular accident, or lower limb amputation.
      Therapists recorded information on teaching methods, perceptions of patient
      knowledge, and expectations for future device use after each treatment session.
      RESULTS: Patients received an average of three dressing and two bathing devices
      for home use. Therapists devoted an average of two and a half sessions (10 min
      average duration) to teach dressing device use and an average of one session (9
      min average duration) to teach bathing device use. Teaching occurred mostly in
      the clinic setting through oral instruction and demonstration. At discharge,
      patients who evaluated devices positively and were evaluated as having a positive
      affect were perceived by the therapists as "having greater knowledge of device
      use." More time was spent teaching those patients with lower Functional
      Independence Measure scores, less positive evaluations of devices, and lower
      affect scores. Family caregivers were involved in one or more dressing sessions
      for 26% of patients and one or more bathing sessions for 36% of patients.
      CONCLUSION: Assistive device training in rehabilitation centers consists largely
      of simulated sessions in the occupational therapy clinic, and patients in the
      study described the instruction they received as "satisfactory." More research is
      needed to study the long-term effectiveness of assistive device training after
      patients return home.

PMID- 9544355
TI  - The fieldwork case study: writing for clinical reasoning.

PMID- 9544354
TI  - The sensory profile: a discriminant analysis of children with and without
      disabilities.
AB  - OBJECTIVES: The purpose of this study was to determine which factors on the
      Sensory Profile, a measure of children's responses to commonly occurring sensory
      experiences, best discriminate among children with autism or pervasive
      developmental disorder (PDD), children with attention deficit hyperactivity
      disorder (ADHD), and children without disabilities. METHOD: Data for three groups
      of children 3 to 15 years of age were used: 38 children with autism or PDD, 61
      with ADHD, and 1,075 without disabilities. The researchers conducted a
      discriminate analysis on the three groups, using group membership as the
      dependent variable and the nine factors of the Sensory Profile as independent
      variables. RESULTS: The analysis yielded two discriminant functions: one that
      differentiated children with disabilities from children without disabilities and
      another that differentiated the two groups of children with disabilities from
      each other. Nearly 90% of the cases were correctly classified with these two
      functions. CONCLUSION: The Sensory Profile is useful for discriminating certain
      groups of children with disabilities. Children with disabilities are accurately
      classified into disability categories with the factors described by previous
      authors. This suggests that patterns of behavior associated with certain
      developmental disorders are reflected in populations of children without
      disabilities. It may be the frequency or intensity of certain behaviors that
      differentiate the groups.

PMID- 9544356
TI  - Covers for a powered wheelchair head-array system.

PMID- 9544357
TI  - Occupational therapy after stroke: are we providing the right services at the
      right time?

PMID- 9544358
TI  - Metal-backed patellar component failure in total knee arthroplasty: a possible
      risk for late infection.
AB  - Between 1985 and 1987, 1837 primary total knee arthroplasty (TKA) prostheses were
      implanted in 1503 patients. Group I included 843 knee with metal-backed patellar
      components (MBPC), and group II included 994 knees with all polyethylene patellar
      components (APPC). Follow-up averaged 5.7 years (range, 2 to 11 years). Twenty
      four MBPC (2.9%) and 16 APPC TKA cases (1.6%) developed deep infection. In the
      time interval between arthroplasty and 2-year follow-up, eight MBPC and 11 APPC
      knees developed deep periprosthetic infection. The difference in the cumulative
      probability of infection between the two groups during this time interval was not
      significant (relative risk, 0.9; 95% confidence interval [CI], 0.3-2.1; P =
      0.73). However, after the 2-year follow-up, 16 MBPC and 5 APPC knees developed
      late infection, and the difference in the cumulative probability of infection
      between the MBPC and APPC knees during this time interval was significant
      (relative risk, 3.1; 95% CI, 1.1-8.5; P = 0.02). Although the mechanism for this
      increased risk of these late infections is not well understood, the attendant
      synovitis, effusion, and relative hyperemia of these knees in the presence of the
      particulate metal and polyethylene debris may increase the potential of bacterial
      seeding to these prostheses. Particulate metal debris has been previously shown
      to suppress bacterial phagocytosis and may play a role in the pathogenesis of
      these infections. We propose that the presence of metal-backed patellar failure
      represents a "prosthesis at risk" for the development of late prosthetic
      infection.

PMID- 9544359
TI  - The effectiveness of gallium citrate Ga 67 radionuclide imaging in vertebral
      osteomyelitis revisited.
AB  - We investigated the role of gallium citrate Ga 67 scanning in diagnosing
      spondylodiscitis. Scans of 41 patients with suspected spondylodiscitis showed
      increased radionuclide uptake in 39 patients; these findings correlated with
      those of magnetic resonance imaging and were proved by biopsy. Two patients with
      negative findings on gallium scans had been strongly suspected of having
      spondylodiscitis; biopsy findings in these patients showed degenerative changes.
      Thirteen patients had negative cultures, while 22 had polygenic infections and 4
      had granulomatous infections. Gallium scanning proved to be 100% sensitive,
      specific, and accurate. The interrater accuracy was excellent. Follow-up scans
      were used to track therapeutic progress. We recommend complementary bone and
      gallium scans in cases of suspected spinal infections. If the scan is positive, a
      biopsy should be done. If the scans are negative, no further investigation is
      needed.

PMID- 9544360
TI  - Percutaneous transpedicular discectomy and drainage in pyogenic spondylodiscitis.
AB  - Spondylodiscitis normally heals itself, but it can cause bone destruction leading
      to deformity and often pain. Debridement of these infections by percutaneous
      transpedicular discectomy with access from adjacent caudal pedicles can
      accelerate natural healing and prevent progression to bone destruction and
      deformity. We outline this technique and discuss a series of 28 patients treated
      using a percutaneous transpedicular approach to obtain culture and histopathology
      specimens, permit drainage and antibiotic irrigation, and provide a channel for
      granulation tissue to invade the infected space. This procedure is safe and
      effective, but it is contraindicated for epidural abscess or granulation tissue
      induced neurocompression and it is ineffective against extensive bone
      destruction.

PMID- 9544361
TI  - In vitro elution of tobramycin and vancomycin polymethylmethacrylate beads and
      spacers from Simplex and Palacos.
AB  - In vitro studies of antibiotic elution from polymethylmethacrylate cement
      comparing Simplex (Howmedica, Rutherford, NJ) with Palacos brands (Richards,
      Memphis, TN) have shown variable results. This study compares the elution of
      tobramycin and vancomycin from Simplex and Palacos beads and spacers. Six
      millimeter beads and spacers were incubated in phosphate-buffered saline, and the
      solution was sampled and changed daily until the concentration of antibiotic fell
      below the minimum inhibitory concentration (MIC) for Staphylococcus aureus. In
      all groups, the Palacos PMMA beads and spacers showed elution at higher levels
      and remained above the MIC longer than did the Simplex PMMA beads. Tobramycin had
      superior elution to vancomycin in all groups. This in vitro study shows that
      Palacos PMMA has superior elution properties to Simplex PMMA in tobramycin and
      vancomycin beads and spacers.

PMID- 9544362
TI  - Relation of surface area to in vitro elution characteristics of vancomycin
      impregnated polymethylmethacrylate spacers.
AB  - To study the relationship between surface area and antibiotic elution from
      antibiotic-impregnated polymethylmethacrylate (PMMA) spacers, a standard block
      spacer made of vancomycin (4 g) and 40 g of PMMA was compared with two unique
      spacer designs, the "donut" and "fenestrated." The spacers were incubated in
      phosphate-buffered saline, which was changed daily, and a microbiologic assay was
      used to measure the antibiotic activity of the eluates. The donut and fenestrated
      spacers had 12% and 40% more surface area than the standard spacer, respectively.
      There was no significant difference, however, in daily elution levels of
      antibiotic between the donut spacer and the standard spacer. The fenestrated
      spacer displayed significantly better elution than either the standard or donut
      spacers, with an average of 20% more antibiotic eluted on any given day.

PMID- 9544363
TI  - The use of dynamic external fixation to obtain tibiocalcaneal fusion after Boyd's
      amputation.
AB  - Two patients sustained severe injuries of the foot and ankle, which were managed
      with Boyd's amputation. A large-pin dynamic external fixator was used to obtain
      fusion between the calcaneus and distal tibia. Boyd's amputation preserves limb
      length and prevents posterior migration of the heel pad (both are disadvantages
      of Syme's amputation). Use of a dynamic external fixator may result in reliable
      and rapid consolidation of the fusion (thus overcoming the disadvantage
      associated with Boyd's amputation).

PMID- 9544364
TI  - Prosthetic joint infection due to Mycobacterium tuberculosis: a case series and
      review of the literature.
AB  - Prosthetic joint replacement is being performed more frequently for patients with
      prior septic arthritis due to Mycobacterium tuberculosis. Prosthetic joint
      infection due to Mycobacterium tuberculosis does occur, but is rare. We report
      the clinical characteristics and outcome of seven cases of Mycobacterium
      tuberculosis prosthetic joint infection seen at our institution over a 22-year
      period and summarize the English-language literature regarding current
      prophylaxis and treatment strategies. Tuberculous prosthetic joint infection most
      often represents reactivation of prior tuberculous septic arthritis. The
      diagnosis of tuberculous prosthetic joint disease is often delayed, because a
      history of prior Mycobacterium tuberculosis septic arthritis is not known.
      Treatment of tuberculous prosthetic joint infection requires a combined medical
      and surgical approach. Removal of the prosthesis has been the traditional
      surgical modality, followed by appropriate antituberculous therapy, but other
      surgical methods have been used successfully in selected cases. To decrease the
      risk of reactivation of infection after prosthesis implantation in patients with
      quiescent tuberculous septic arthritis who have not received prior
      antituberculous therapy, consideration should be given to preoperative or
      perioperative antituberculous prophylaxis.

PMID- 9544365
TI  - Isolated plantar fracture-dislocation of the middle cuneiform.
AB  - A previously unreported case of plantar dislocation of the medial cuneiform is
      described. The significance of this injury does not lie in its rarity, but in the
      amount of force required to cause such an injury. This large force may cause bony
      disruption, along with significant soft-tissue injury, and even compartment
      syndrome. Analysis of the preoperative evaluation, including the importance of a
      computed axial tomographicscan, operative intervention, and postoperative care
      are discussed.

PMID- 9544366
TI  - Technique for endoscopic femoral interference screw placement during anterior
      cruciate ligament reconstruction.
AB  - Proper femoral interference screw placement during endoscopic anterior cruciate
      ligament reconstruction is technically demanding. Potential graft injury and the
      high incidence of screw divergence can be decreased by using the tibial tunnel
      for screw advancement, as described in this article.

PMID- 9544367
TI  - Pain management in orthopedics.

PMID- 9544368
TI  - Pain management in orthopedics.

PMID- 9544369
TI  - Data about 154 children and adolescents reporting sexual assault.
AB  - Sexual assaults on girls occur at an alarming rate representing a significant
      public health problem, but difficulties in correctly identifying the problem,
      managing the child and reporting for legal purposes have been recognized. We
      describe data obtained on 154 recent cases of child and adolescent sexual
      assault. Results indicate that those at highest risk of sexual assault are girls
      at age of 11-15 years having a stepfather, although the most girls at age of > 15
      were assaulted by strange men with higher incidence of cross-race assault. Over a
      quarter of girls showed signs of physical trauma with face and neck as most
      common site of contact. A total of 17.5% reported threat of violence or with
      weapons and 9.7% had alcoholic influence. Pattern and incidence of genital
      injuries were described.

PMID- 9544370
TI  - Retrospective study of outcome on vaginal and abdominal delivery in twin
      pregnancy in which twin 1 is presenting by the breech.
AB  - We retrospectively reviewed the perinatal outcome of twin pregnancies cohere the
      first baby was presenting by the breech. 21 were delivered vaginally and 37
      abdominally. Differences in perinatal outcome, as measured by Apgar score and
      mortality, were not apparently different.

PMID- 9544371
TI  - A randomized study of local or general anesthesia for laser conization of the
      cervix.
AB  - Laser Conization of the cervix was performed in both inpatient and outpatient
      settings with either local or general anesthesia. All of the patients included
      had abnormal cervical smears, abnormal colposcopic findings and were allocated to
      one of two groups, A and B. Patients in group A had general anesthesia while
      patients in group B had only local anesthesia. A standard operative technique,
      was used and all patients had estimation of blood loss, recording of operative
      time, surgical suite time, anesthesia induction time, and assessment of
      postoperative pain and morbidity. Statistical analysis was performed using the
      student t-test. We concluded that laser conization of the cervix can be performed
      more cheaply with local anesthesia than with general anesthesia and with little
      discomfort, less nausea, and vomitting.

PMID- 9544372
TI  - Endometrial cancer in patients undergoing diagnostic curettage.
AB  - We made a retrospective review of in 2769 patients in whom curettage was
      performed. Of 1468 women under 50 years of age, only one (0.08%) had endometrial
      cancer. Of 834 patients presenting with postmenopausal bleeding 31, (3.7%) had
      endometrial cancer.

PMID- 9544373
TI  - Nine year survey of 138 ectopic pregnancies.
AB  - During the nine years (1986-1994), 138 women underwent surgery for ectopic
      pregnancies (One for every 213 deliveries). The commonest presenting symptom was
      abdominal pain (96%) followed by vaginal bleeding (83%). Four patients were
      asymptomatic and were diagnosed at a routine antenatal ultrasound scan. The most
      frequent physical findings were abdominal tenderness (87%) and followed by
      adnexal tenderness (57%). Histories of infertility in 17%, use of intrauterine
      contraceptive device (13%), and previous ectopic pregnancy in 11% were elicited.
      Eleven patients (8%) had a false negative urinary pregnancy test and subsequently
      required surgery. The ectopic pregnancies were tubal in 97% of the cases. There
      were 3 ovarian ectopics and one cervical ectopic.

PMID- 9544374
TI  - Endometriosis diagnosed by laparoscopy in adolescent girls.
AB  - 105 adolescent girls with mean age of 17.3 (11-19) years had
      laparoscopy/pelviscopy between 1996 and 1997. In 37 cases, endometriosis was
      diagnosed (35.2%). The majority of the girls (32.4%) presented with endoscopic
      endometriosis classification (EEC) stage I. 2.8% of the girls had stage EEC II.
      The lesions involved one site or pelvic organ (64.8%) with a mean age of 18.7 (14
      19) years. In 35.2% of cases, the lesions were at multiple sites with a mean age
      of 16.9 (11-19) years. Indications for laparoscopy included chronic or acute
      pelvic pain and right-sided lower abdominal pain. Endometriotic lesions were
      found in the pouch of Douglas (64.8%), uterosacral ligaments (37.8%), and ovarian
      fossa (24.3%), 42.8% of directed biopsies were positive. Endocoagulation of the
      endometriotic lesions was performed in 91.9% of cases.

PMID- 9544375
TI  - Molecular analysis of the androgen receptor gene in 4 patients with complete
      androgen insensitivity.
AB  - Androgen insensitivity syndromes are due to defects in the androgen receptor
      gene. In this study, we analyzed the androgen receptor gene in four cases with
      complete androgen insensitivity syndrome. In patient 1, one substitutional
      mutation [arginine (codon CGC) to cysteine (codon TGC) at position 774] of exon F
      was identified. This position was located in the hormone binding domain and
      appeared to be one hot spot of mutations because the mutations at the same
      position in several unrelated cases were reported before. In patient 2, one
      substitutional mutation [tyrosine (codon TAT) to cysteine (codon TGT) at position
      571] of exon B was identified. This position was located in the DNA binding
      domain. In patients 3 and 4 (siblings), one substitutional mutation [arginine
      (codon CGA) to glutamine (codon CAA) at position 752] of exon E was identified.
      Taken together, these abnormalities might be related to the pathogenesis of
      complete androgen insensitivity.

PMID- 9544376
TI  - Preeclampsia with fetal death in a patient with schistosomiasis japonica.
AB  - A case of preeclampsia with fetal death at 32 weeks' gestation is reported. Liver
      examination of the patient revealed network patterns on ultrasonography and
      linear calcifications on unenhanced CT scans in the liver. These findings are
      typical of those of chronic schistosomal infection. Indeed, liver biopsy
      specimens showed eggs of schistosoma japonicum. We diagnosed her case as
      preeclampsia with liver cirrhosis due to chronic schistosomiasis japonica.
      Schistosomal placentitis may have been present and may have contributed to
      preeclampsia and fetal death.

PMID- 9544377
TI  - Persistent mullerian duct syndrome.
AB  - We report an 18-month old male presenting with a right-sided inguinal hernia and
      undescended testes. At herniotomy, a uterus and two fallopian tubes were found in
      the pelvic peritoneum adjacent to the two gonads which received their blood
      supply partly along the mullerian duct remnants. The gonads were testes by
      histological examination. Bilateral orchiopexy was performed without removal of
      the mullerian structures for fear of jeopardizing the testicular blood supply.
      The diagnosis of persistent mullerian duct syndrome was confirmed postoperatively
      by genetic and hormonal investigations.

PMID- 9544378
TI  - Antimicrobial resistance and Helicobacter pylori: impacts on current and future
      therapies.

PMID- 9544379
TI  - Systemic lupus erythematosus (SLE): changing concepts and challenges for the new
      millennium.
AB  - SLE is still the prototype experimental animal and human autoimmune disease. The
      clinical manifestations are so diverse that some have come to regard it as the
      incumbent 'luetic heir apparent' of the late 20th century. The aberrations of the
      immune disturbance have up until now defied clear explanation but have certainly
      generated a level of academic and research interest far greater than the
      frequency of the disease would initially suggest. The clear understanding of the
      immune derangements in SLE will probably lead to the understanding of the core
      mechanisms of the immune system and thus to better ways of its specific
      manipulation in the management of many other conditions including cancer.
      Research currently being undertaken on the mechanisms of control of
      immunologically mediated inflammation and the possible use of immunogenetic
      therapy in the treatment of various forms of SLE will hopefully further improve
      SLE related morbidity and mortality.

PMID- 9544380
TI  - Short duration therapy for Helicobacter pylori in Western Australia: the impact
      of metronidazole resistance.
AB  - BACKGROUND: Limited Australian data are available on either short duration
      therapy for Helicobacter pylori infection, or the impact of metronidazole
      resistance on the outcome of treatment. AIM: To compare the efficacy of two
      treatment regimens and determine the influence metronidazole resistance has on
      clearing H. pylori infection. METHODS: Eighty patients with H. pylori infection
      proven at upper gastrointestinal endoscopy, none of whom had previously received
      therapy for H. pylori, were randomised to one week therapy with either bismuth
      subcitrate one tablet qid, tetracycline 500 mg qid and metronidazole 400 mg tds
      (BTM), or lansoprazole 30 mg bd, amoxycillin 500 mg qid and metronidazole 400 mg
      tds (LAM). Effectiveness of therapy was measured by C14-urea breath test at six
      weeks. RESULTS: On an intention-to-treat basis, clearance of infection was
      achieved in 17 of 32 (53%; 95% CI: 35-71%) evaluable patients receiving BTM and
      32 of 46 (70%, 54-82%) patients receiving LAM (p = 0.16). Metronidazole
      resistance was found in 32 of 65 (49%) patients in whom H. pylori was isolated by
      culture. On a per-protocol basis, of patients who had metronidazole sensitive
      strains of H. pylori 23 of 24 (96%) cleared infection after therapy with either
      BTM or LAM, compared with 14 of 24 (58%) who were metronidazole resistant (p =
      0.004). Clarithromycin resistance was not found in 45 patients tested.
      CONCLUSIONS: In Western Australia clearance rates of H. pylori infection, after
      one week of BTM or LAM, are lower than in other published series. The high
      incidence of metronidazole resistance is the main determinant of our relatively
      poor eradication rates.

PMID- 9544381
TI  - Pregnancy outcome in systemic lupus erythematosus (SLE): a review of 54 cases.
AB  - AIM: To compare the pregnancy outcome, in particular gestational age and birth
      weight in women with systemic lupus erythematosus (SLE) diagnosed before and
      after pregnancy, and to review data on presence or absence of the
      antiphospholipid (aPL) antibody and flares of disease activity. METHOD: Case
      histories were reviewed of women with a diagnosis of SLE and an obstetric event
      attending Monash Medical Centre (MMC) over an eight year period (1988-96). Fifty
      four pregnancies in 28 women were studied, with 44 occurring after the diagnosis
      of SLE (Group 1) and ten prior to the diagnosis of SLE (Group 2). RESULTS: In
      Group 1 there were 25 live births (63%) with 16 full term and nine premature
      deliveries, 12 spontaneous abortions, three foetal deaths in utero and four
      elective terminations. In Group 2 there were seven live births (70%), two
      spontaneous abortions and one foetal death in utero. The mean gestational age of
      live births was 35.8 weeks and 39.2 weeks respectively (p < 0.001). The mean
      birth weight of live births was 2448 g and 3030 g respectively (p < 0.023). a PL
      antibodies were positive in eight of 26 women tested with three live births and
      were negative in 18 of 26 women with 12 live births. Flares of disease activity
      occurred in 17 of 28 pregnancies. CONCLUSION: Pregnancy in women with a
      predisposition to SLE have a high risk of an adverse outcome. Clinical disease
      confers an additional risk. The mean gestational age and birth weight were
      significantly less in women with established disease. Mild flares in disease
      activity resulted in a favourable outcome while renal flares had a worse outcome.

PMID- 9544382
TI  - Staphylococcal bacteraemia: the hospital or the home? A review of Staphylococcus
      aureus bacteraemia at Concord Hospital in 1993.
AB  - AIMS: To examine the risk factors for, and the complications and mortality of,
      Staphylococcus aureus bacteraemia. METHODS: A retrospective case review of
      patients with S. aureus bacteraemia in 1993 diagnosed at the Concord Repatriation
      General Hospital, Sydney. RESULTS: Of 104 cases reviewed, 32 were due to
      methicillin resistant S. aureus (MRSA), 73 were due to methicillin sensitive S.
      aureus (MSSA) and one was a dual infection. Twenty-eight of the bacteraemias were
      community-acquired, including one case of MRSA, and 76 were hospital-acquired;
      38% had an implanted prosthetic device or graft. The average age (68 years),
      incidence of underlying diseases and hospitalisation in the past month (26%) did
      not differ between MRSA and MSSA groups. MRSA was more likely in patients with
      recent broad-spectrum antibiotic use (53% vs 0, p < .01). Vascular access was the
      commonest source of sepsis (61%) but in community-acquired cases the source was
      unknown in 50%. Use of central line access was more predictive of MRSA infection
      (75% vs 49%, p = .018). In hospital-acquired infection, MRSA sepsis occurred
      later in the course of the admission (26 days vs eight days, p < .01). Directly
      attributable mortality was highest in MRSA and community-acquired MSSA infection
      (9% and 11%) compared with hospital-acquired MSSA infection (1%). CONCLUSIONS:
      Nosocomial S. aureus bacteraemia, particularly MRSA, is a major source of
      preventable morbidity, which could be addressed by improved infection control of
      MRSA, antibiotic use and attention to central line catheter use.

PMID- 9544383
TI  - Long term follow-up of CEOP in the treatment of HIV related non-Hodgkin's
      lymphoma (NHL).
AB  - BACKGROUND: The development of non-Hodgkin's lymphoma (NHL) in AIDS conveys a
      poor prognosis with less than 10% of patients surviving beyond two years. These
      tumours are generally aggressive and often require systemic chemotherapy to bring
      about effective palliation. AIMS: To report on the long term follow-up of
      patients with HIV related NHL treated with CEOP chemotherapy. METHODS: This is a
      retrospective analysis of a group of 18 patients treated at two institutions
      between October 1990 and 1992 with modified CEOP chemotherapy. Doses were
      calculated using cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, vincristine 2
      mg and prednisone 75-100 mg x five days, however initial doses of
      cyclophosphamide and epirubicin were modified to 50-75% of calculated dose.
      RESULTS: Seventeen of the 18 patients were male, one female; age range 26-79
      (median 36 years); seven with immunoblastic, three Burkitt's, one Ki-1
      (anaplastic), six diffuse large cell, and one mixed large and small cell. Eight
      patients (44%) achieved a complete remission, with seven patients (39%) achieving
      a partial remission, for an overall response rate of 83% (95% CI = 59-96%).
      Survival ranged from three-35 months (median nine months). Interestingly, four
      patients (22%) survived more than two years (median 31 months), three remaining
      in complete remission at the time of death. Generally therapy was well tolerated
      and toxicity was manageable. CONCLUSIONS: CEOP is an effective, tolerable and
      safe regimen and our long term follow-up suggests that there is a small sub
      population of patients with HIV and lymphoma who may have a better prognosis and
      as such would clearly benefit from systemic chemotherapy as a means of prolonging
      survival and not simply palliation.

PMID- 9544384
TI  - Comparison of thallium-201 and gallium-67 scintigraphy in the evaluation of non
      Hodgkin's lymphoma.
AB  - BACKGROUND: Gallium-67 (Ga-67) is widely used in the assessment of patients with
      lymphoma. Although highly sensitive in Hodgkin's disease and high grade non
      Hodgkin's lymphoma (NHL), its sensitivity is reported to be reduced in lower
      grades of NHL. Several series have suggested that thallium-201 (Tl-201) may be
      more useful than Ga-67 in the evaluation of low and possibly intermediate grade
      NHL. AIM: To compare the sensitivity and relative avidities (uptakes) of Tl-201
      and Ga-67 in patients with NHL. METHODS: A total of 36 pairs of studies were
      performed in 33 patients (14 male: 19 female; age range 16-84 years, mean 55
      years). All had whole body Ga-67 (400 MBq) and Tl-201 (100-200 MBq) studies
      (interval 0-three days) which were read by two experienced nuclear medicine
      physicians blinded to clinical history and results of other investigations.
      RESULTS: Tl-201 had a higher sensitivity and avidity than Ga-67 in patients with
      low grade NHL. In contrast, Ga-67 was slightly more sensitive and had a higher
      avidity in patients with both intermediate and high grade NHL. CONCLUSIONS: We
      conclude that Tl-201 is more sensitive and avid for low grade NHL than Ga-67 and
      that consideration should be given to its use in this condition in conjunction
      with Ga-67 as it may provide complementary information. Routine use in
      intermediate grade NHL is less convincing as Ga-67 was superior in most cases. Ga
      67 is more sensitive than Tl-201 in assessment of high grade NHL.

PMID- 9544385
TI  - Graves' ophthalmopathy: pathogenesis and clinical implications.

PMID- 9544386
TI  - The Everett Magnus Oration. Euthanasia and the law: crossing the Rubicon?

PMID- 9544387
TI  - Euthanasia--crossing the Rubicon or at the cross roads?

PMID- 9544388
TI  - Euthanasia: over the Rubicon already?

PMID- 9544389
TI  - Deliberate self-poisoning with eucalyptus oil in an elderly woman.

PMID- 9544390
TI  - Heparin-induced skin lesions.

PMID- 9544391
TI  - Very rapid echocardiographic appearance of Aspergillus endocarditis.

PMID- 9544392
TI  - Skull metastases masquerading as cerebral secondaries in patients with cancer.

PMID- 9544393
TI  - Acute rheumatic fever (ARF) in non-aboriginal patients in the Northern Territory.

PMID- 9544394
TI  - Lupus anticoagulant antiprothrombin syndrome.

PMID- 9544395
TI  - Implementation of guidelines for no-CPR orders.

PMID- 9544396
TI  - Implementation of guidelines for no-CPR orders.

PMID- 9544397
TI  - Haemolytic uraemic syndrome with acute oedematous pancreatitis.

PMID- 9544398
TI  - Giant cell arteritis (GCA) presenting with severe aortic regurgitation and a
      normal ESR.

PMID- 9544399
TI  - Insulin requiring diabetes as a manifestation of Munchausen's syndrome.

PMID- 9544400
TI  - Multi-focal Salmonella typhi infection.

PMID- 9544401
TI  - Parallel implementations of individual-based models in biology: bulletin- and non
      bulletin-board approaches.
AB  - Particle-based models are simulations in which the discrete representation of
      physical phenomenon involves interacting particles. This paper studies the
      efficiency of two different methods of implementing these models on a network of
      UNIX workstations. Two data parallel methods of modeling particles are tested:
      bulletin-board and non-bulletin-board. In the former method, the programs
      communicate through a logically shared, associative memory called a bulletin
      board. The simulated particles are distributed among the workstations dynamically
      as the processing load on the processors changes. In the latter method, the
      particles are divided amongst the networked workstations statically at load time.
      The simulated system is a collection of ants moving and foraging in a two
      dimensional space. This paper analyzes and compares the execution times of both
      implementations for different combinations of particles and number of
      workstation, using speed-up, tuple granularity and communication cost as
      measures. Analysis shows that the bulletin-board method is better for particle
      based simulations when the correct granularity is chosen.

PMID- 9544402
TI  - An interdisciplinary approach towards a theory of consciousness.
AB  - Instead of attacking the difficult problem of consciousness or self-consciousness
      directly, the theory is based on the more basic concept of reflection. A concept
      of reflection is suggested on four levels (recursion, reflective thinking, self
      reflection, intersubjective reflection). We propose the glial-neuronal
      interaction as a neurobiological substrate for reflection processes. It is
      assumed that glia have a boundary-setting function (scaffolding,
      compartmentalization) in the spatio-temporal interaction with the neurons. This
      function could be a possible mechanism of 'dividing' the brain into different
      self-systems each with their own capacity of self-organization. Although the
      brain's different self-systems are normally integrated, they may disintegrate and
      show themselves in special states of the brain (e.g. multiple personality
      disorder). A tree of reflection consisting of a number of places (ontological
      loci) on which reflection processes of varying complexity take place, is
      suggested as the formal model. Finally, the problem of self-conscious qualitative
      experience (Qualia) is discussed in terms of the reflection model.

PMID- 9544403
TI  - Characteristics of ionic transport processes in fish intestinal epithelial cells.
AB  - A general mathematical version of the cell model of a leaky epithelium for the
      NaCl absorption is presented, analysed and integrated numerically. The model
      consists in the adequate differential equations that describe the rate of change
      of the intracellular ion concentrations and are expressed in strict accordance
      with the law of mass conservation. The model includes many state variables
      representing ion concentrations, the cell volume, and membrane potentials. Ion
      movements are described by the Michaelis-Menten kinetics or by the constant field
      flux equation (Goldman-Hodgkin-Katz). In this paper, we model the intracellular
      ion concentrations, change in the cell volume, the transmembrane flux and
      membrane potentials of intestinal epithelium of both fresh water and sea water
      fish, and generate several simulations (in both the steady state and the
      transient state analysis) that appear to accord with prior experimental data in
      this area. For the ion movements of the sea water fish intestine, there were
      included a Na+/K+ pump, a K(+)-Cl- symport system, the K+ and Cl- channels in the
      basolateral membrane, whereas a Na(+)-K(+)-2Cl- cotransporter for NaCl absorption
      and K+ channels are located in the apical membrane. In the fresh water fish
      intestinal cells, the NaCl absorption is performed by two coupled antiporters
      Na+/H+ and Cl-/HCO3- presumably responsible for the intracellular pH regulation.
      In this type of cells, Na+ and K+ channels are located within the apical
      membrane, whereas Cl- channels are located within the basolateral membrane. The
      osmotically induced water transport across the apical and basolateral membranes
      has been taken into account as well. The simulations plot the steady state values
      for membrane potential difference, short-circuit current and intracellular ionic
      concentrations using the magnitude of the transmembrane flux through the Na+/K+
      pump and Na(+)-K(+)-2Cl- cotransporter, or the basolateral Cl- permeability as
      dependent variables. The model behaves appropriately with regard to several
      experimental studies regarding the hyperpolarization (sea water fish intestine)
      and depolarization (fresh water fish intestine) of the apical membrane potential
      and inhibition of the short-circuit flux with reduced NaCl absorption. The model
      is also used to make several analytical predictions regarding the response of the
      membrane potential and ionic concentrations to variations in the basolateral Cl-
      flux. Furthermore, maintaining conservation of both mass and electroneutrality
      and taking into account the osmolar forces is an important advantage, because it
      allows a rigorous analysis of the relationship between membrane potential
      difference, volume and flux. The model can be used in the analysis and planning
      of the experiments and is capable of predicting the instantaneous values of ionic
      fluxes and intracellular concentrations and of cell volume.

PMID- 9544404
TI  - Enzyme-dependent responses of stimuli-sensitive systems.
AB  - The methods of creating of systems where properties depend both on an outer
      physical signal and enzyme activity are discussed. The construction of a
      conjugation chain between responses of stimuli-sensitive materials and urea
      hydrolysis catalyzed with urease is demonstrated on the basis of light- and
      thermoreversible polymeric matrices.

PMID- 9544405
TI  - Diffusion theory, the cell and the synapse.
AB  - The possibility exists that the cell internum is far more highly organised right
      down to the molecular level than was hitherto appreciated, to the point where
      ideas of a relatively solid-state chemistry model have been entertained (Coulson,
      R.A., 1993. The flow theory of enzyme kinetics--a role of solid geometry in the
      control reaction velocity in live animals. Int. J. Biochem. 25, 1445-1474). This
      contrasts sharply with the traditional dogma that diffusion is the mechanism by
      which molecules interact within an aqueous solution of the cell internum,
      although it should have been clear from an early stage that diffusion could not
      play other than a very restricted role in metabolic regulation. When physicists
      began to question certain aspects of the fundamental Law of Heat Conductance
      formulated over 170 years ago by Fourier, Diffusion Theory was also implicated
      (Maddox, J., 1989. Heat conductance is a can of worms. Nature 338, 373), and
      application of Fick's Laws of Diffusion to living systems criticised (Agutter
      P.S., Malone, P.C., Wheatley, D.N., 1995. Intracellular transport mechanisms: a
      critique of diffusion theory. J. Theoret. Biol. 176, 261-272). While we have
      argued (Wheatley, D.N., Malone, P.C., 1993. Heat conductance, diffusion theory
      and intracellular metabolic regulation. Biol. Cell 79, 1-5) that diffusion cannot
      be prevented from occurring, we found that, irrespective of whether it was a
      valid theory, diffusion was of little relevance in most actively metabolising
      cell systems. However, diffusion is still perceived as essential for interacting
      molecules to demonstrate their specificities. Any new model of the internal state
      of the living cell has to resolve this dilemma. The question also relates to
      molecular movement and ligand-receptor interactions outside the cell. In looking
      at this situation, attention was paid to one site in the body in which diffusion
      has long been assumed to be essential, namely in the passage of the chemical
      transmitter between one neurone and the next across the synaptic cleft. A
      detailed examination of this assumption has helped to identify one possible place
      in which the importance of diffusion over a distance of no more than 20-30 nm
      occurs, although objections to diffusion being involved have been raised. The
      outcome, however, only re-enforces the conviction that diffusion has little role
      in metabolic activity and is normally 'assisted' in almost all aspects of cell
      physiology.

PMID- 9544406
TI  - The role of the genetic code in generating new coding sequences inside existing
      genes.
AB  - The genetic code has a very interesting property--it generates an open reading
      frame (ORF) inside a coding sequence, in a specific phase of the antisense strand
      with much higher probability than in the random DNA sequences. Furthermore, these
      antisense ORFs (A-ORFs) possess the same features as real genes--the asymmetry in
      the nucleotide composition at the first and second positions in codons. About two
      thirds of the 2997 overlapping ORFs in the yeast genome possess this feature.
      Thus, the question arises: has this feature of the genetic code been exploited in
      the evolution of genes? We have searched the FASTA data bases for homologies with
      the antisense translation products of a specific class of genes and we have found
      some sequences with relatively high homology. Many of them have scores which
      could be randomly found in the searched data bases with a probability lower than
      10(-6). We conclude that some genes could arise by positioning a copy of the
      original gene under a promoter in the opposite direction in such a way that both,
      the original gene and its copy initially use the same nucleotides in the third,
      degenerated positions in codons.

PMID- 9544407
TI  - Esophageal ulcer.

PMID- 9544408
TI  - Collagenous colitis.

PMID- 9544409
TI  - Methotrexate therapy.
AB  - Methotrexate may be very helpful for your illness if proper care is taken in the
      use of this medication. Follow your physician's instructions faithfully. Take
      methotrexate weekly as directed. Notify your physician at once if an accidental
      overdose is suspected or if you develop fever, cough or shortness of breath. If
      you develop vomiting, there is a change in your pattern of diarrhea or you
      suspect that you are dehydrated, notify your physician before taking the next
      dose of methotrexate. Do not start or change any medicine without first checking
      with your physician. Avoid or severely restrict alcohol, including wine and beer.
      Obtain the blood tests ordered by your physician. Avoid pregnancy during and for
      several months after taking methotrexate. Keep methotrexate out of the reach of
      children. It has been prescribed for your current medical problem and must not be
      given to other people.

PMID- 9544410
TI  - Canadian Helicobacter pylori consensus conference. Canadian Association of
      Gastroenterology.
AB  - These guidelines were created to dispel confusion and provide guidance about how
      the isolation of Helicobacter pylori infection has led to new opportunities and
      initiatives to improve patient care. The guidelines are designed for practical
      application in management decisions, but must remain flexible and amenable to
      change with new information. Updated versions of the recommendations are
      anticipated. Although it is now clear that H pylori is a major gastrointestinal
      pathogen, the extent of the clinical consequences posed by this microorganism has
      yet to be fully defined.

PMID- 9544411
TI  - A cost-utility analysis comparing omeprazole with ranitidine in the maintenance
      therapy of peptic esophageal stricture.
AB  - BACKGROUND: Recent studies have suggested that patients receiving omeprazole for
      prophylaxis against peptic esophageal stricture recurrence have less dysphagia
      and require fewer repeat dilations than patients receiving ranitidine. OBJECTIVE:
      To estimate the incremental utility gain and associated incremental cost of
      omeprazole compared with those of ranitidine for the maintenance therapy of
      patients with peptic stricture who required esophageal dilation. METHODS:
      Decision analysis using SMLTREE software was used to compare the incremental cost
      utility of omeprazole 20 mg once daily with that of ranitidine 150 mg bid for one
      year. Variables were estimated from the literature, hospital data, and utility
      analyses involving patients with peptic stricture and health professionals. The
      primary outcome measure was cost per quality-adjusted life-years (QALYs) gained.
      RESULTS: The incremental cost of omeprazole compared with that of ranitidine was
      $556 per patient treated. The incremental utility gain of omeprazole was 0.0112
      QALYs. Overall, the incremental cost:utility ratio of omeprazole in the
      maintenance therapy of patients with peptic stricture was $49,600 per QALY
      gained. A sensitivity analysis revealed that the estimates with the greatest
      impact on the cost:utility ratio were disutility associated with dysphagia and
      dilation, the probability of requiring redilation and the cost of medications.
      CONCLUSIONS: Omeprazole 20 mg once daily is associated with greater utility and
      higher cost than ranitidine 150 mg bid when used as prophylaxis against stricture
      recurrence. Omeprazole may be considered clinically and economically sufficient
      enough to warrant widespread use in this setting.

PMID- 9544412
TI  - Combination ciprofloxacin and metronidazole for active Crohn's disease.
AB  - Recent experimental evidence underscores the contribution of intestinal bacteria
      to the inflammatory process of Crohn's disease. This open study examined the
      efficacy and safety of combination ciprofloxacin and metronidazole for patients
      with active Crohn's disease of the ileum and/or colon. Seventy-two patients with
      active Crohn's disease of the ileum (n = 27), ileocolon (n = 22) or colon (n =
      23) were treated with ciprofloxacin 500 mg bid and metronidazole 250 mg tid for a
      mean of 10 weeks. Clinical remission was defined as a Harvey-Bradshaw index of
      three points or less; an index reduction of at least three points indicated a
      clinical response. Clinical remission was observed in 49 patients (68%), and 55
      patients (76%) showed a clinical response. A clinical response was noted in 29 of
      43 patients (67%) who were not taking concurrent prednisone treatment and in 26
      of 29 patients (90%) receiving prednisone (mean dose of 15 mg/day). A clinical
      response also occurred in a greater proportion of patients with colonic disease,
      with or without ileal involvement (84%), compared with patients with ileal
      disease alone (64%), and in patients without resection (86%) compared with those
      with previous resection (61%). Five patients discontinued antibiotics because of
      adverse events. After a mean follow-up of nine months, clinical remission was
      maintained in 26 patients off treatment and in 12 patients who continued
      antibiotic therapy. Ciprofloxacin in combination with metronidazole is well
      tolerated and appears to play a beneficial role in achieving clinical remission
      for patients with active Crohn's disease, particularly when there is involvement
      of the colon.

PMID- 9544413
TI  - Antibody levels in Ethiopian children five years after vaccination with two
      different doses of hepatitis B vaccine: is there a need for booster vaccine?
AB  - It was hypothesized that, following effective initial vaccination, a booster dose
      of hepatitis B vaccine will not be necessary in areas of hyperendemicity for
      hepatitis B virus (HBV) infection. A total of 314 Ethiopian children, ranging
      from two to 14 years old, were alternatively vaccinated with 10 and 20 micrograms
      hepatitis B vaccine doses, using the initial, one- and six-month schedule. Five
      years later, 210 of the vaccinees were retested for anti-HBV surface antibody
      titres. Both 10 and 20 micrograms doses of hepatitis B rDNA yeast vaccine were
      equally immunogenic and protective against HBV infection for at least five years
      despite marked reduction of mean antibody levels and geometric mean titres, with
      11% of the vaccinees showing antibodies below the protective level. For firm
      further recommendations a longer follow-up period of vaccinees is suggested.

PMID- 9544414
TI  - Eligibility and exclusion of hemochromatosis patients as voluntary blood donors.
AB  - BACKGROUND: Hereditary hemochromatosis patients are excluded in many countries as
      voluntary blood donors. In 1991, changes in the Canadian Red Cross policy allowed
      healthy hemochromatosis patients to become voluntary donors. STUDY DESIGN AND
      METHODS: The medical histories of 208 hemochromatosis patients were evaluated for
      eligibility for blood donation from a large prospective database of
      hemochromatosis patients. A survey that determined the success or exclusion of 81
      patients for blood donation and the reasons for their exclusion based on Canadian
      Red Cross donor exclusion criteria was analyzed. RESULTS: Of 208 hemochromatosis
      patients, 140 (67%) were eligible for blood donation. Criteria for exclusion were
      other illnesses excluded by Canadian Red Cross criteria and the use of
      contraindicated medications. Fifty-one per cent of patients had attempted to
      donate blood, with only 7% being successful. CONCLUSIONS: A large number of
      potential blood donors are excluded from blood donation inappropriately despite
      changes in eligibility criteria to the contrary. Further public and health
      education is needed to increase awareness and, thus, increase blood donation by
      potential donors.

PMID- 9544415
TI  - Liver transplantation for neuropsychiatric Wilson disease.
AB  - Although neuropsychiatric manifestations are prominent in some patients with
      Wilson disease, there is little published information regarding the efficacy of
      liver transplantation for these patients. A 22-year-old male with advanced
      neurological impairment and prominent psychiatric manifestations due to Wilson
      disease who underwent liver transplantation is presented. After transplantation,
      the ceruloplasmin and copper studies normalized and eventually the Kayser
      Fleischer rings disappeared. Neurological recovery was very slow and incomplete,
      and his behavioural and personality disorder was entirely unaffected. He
      committed suicide 43 months post-transplantation. A review of the small number of
      related published cases in the English language literature shows variable
      neurological recovery post-transplantation, but the course of psychiatric
      manifestations is virtually never described. This case suggests that one must be
      cautious regarding liver transplantation for Wilson disease in patients with
      prior psychiatric manifestations. Aggressive medical management is likely to be
      preferable in most cases.

PMID- 9544416
TI  - Hemorrhagic intestinal Henoch-Schonlein purpura complicated by cytomegalovirus
      infection.
AB  - A 54-year-old man on hemodialysis for acute chronic renal failure and on
      corticosteroids for Henoch-Schonlein purpura developed massive hematochezia.
      After extensive clinical investigation, an ileal bleeding site was identified and
      surgically removed. Pathological examination of the diseased bowel segment
      revealed an extensive vasculitis with mucosal ulceration attributable to Henoch
      Schonlein purpura as well as florid cytomegalovirus infection.

PMID- 9544417
TI  - Obscure gastrointestinal bleeding from an ampullary tumour in a patient with a
      remote history of renal cell carcinoma: a diagnostic conundrum.
AB  - Metastasis of renal cell carcinoma to the ampulla of Vater is a rare occurrence.
      The outlined case, which presented as an upper gastrointestinal bleed, is only
      the eighth such reported case in the English-language literature. This case is
      the longest reported time interval between surgical nephrectomy to presentation
      with ampullary metastasis at 17.5 years. The ampullary source of bleeding in this
      case was initially obscure and missed by conventional gastroscopy. Diagnosis was
      made with a side-viewing endoscope, emphasizing the usefulness of this instrument
      in the investigation of active bleeding from a small bowel source.

PMID- 9544418
TI  - A Canadian physician survey of dyspepsia management.
AB  - OBJECTIVE: To determine the management of patients with new onset dyspepsia by
      Canadian family physicians. METHODS: A survey was mailed to 195 family physicians
      in August 1995 to identify how they manage dyspepsia in patients according to
      four scenarios: based on presenting symptoms alone; assuming Helicobacter pylori
      positive; known to be H pylori-negative; and endoscopically confirmed nonulcer
      dyspepsia. RESULTS: A total of 170 of 195 physicians (87.2%) completed the
      survey. Physicians reported that 7.3% of their practice is devoted to dyspepsia
      and 23% of these dyspeptic patients present for the first time. Ninety-three per
      cent of family physicians find a symptom classification of ulcer-, reflux- and
      dysmotility-like dyspepsia helpful. The majority of patients are advised to make
      life-style changes and are treated with antacids or empiric drug therapy. A H2
      receptor antagonist was the drug of choice for ulcer and reflux-like dyspepsia,
      while prokinetics were often used for reflux and dysmotility-like dyspepsia.
      After failure of initial treatment, patients were given another course of empiric
      treatment, commonly with cisapride or omeprazole. Family physicians estimated
      that the mean time to obtain a gastrointestinal consult was five weeks, and 70%
      indicated that this time to consult adversely influenced their decision to refer.
      If this time was reduced to less than two weeks, responding physicians would
      consider referring all eligible patients. On average, two to 2.5 courses of
      empiric therapy were given before referral. If H pylori status was known, fewer
      empiric treatments (mean 1.8) were given before gastroenterological referral
      compared with the other scenarios. If the patient had nonulcer dyspepsia, 30% of
      family physicians provided reassurance only and did not prescribe empiric drug
      treatment. CONCLUSIONS: Most newly dyspeptic patients in Canada are treated with
      empiric therapy according to symptom classification and referred for endoscopy
      after an average two to 2.5 treatment courses.

PMID- 9544419
TI  - Significance of nitric oxide in carcinogenesis, tumor progression and cancer
      therapy.

PMID- 9544420
TI  - Molecular biology of nitric oxide synthases.
AB  - Nitric oxide (NO) is a potent biologic mediator with diverse physiologic and
      pathophysiologic roles. NO is produced from L-arginine by the family of nitric
      oxide synthase (NOS) enzymes, forming the free radical NO and citrulline as
      byproduct. Three distinct isoforms of the NOS enzyme have been isolated and
      represent the products of three different genes. Two of the NOS enzymes are
      continuously present and are termed constitutive NOS (cNOS). One cNOS enzyme was
      identified in neurons, and the other in endothelial cells. The two cNOS enzymes
      are contrasted with the third NOS isoform, inducible NOS, which is not typically
      expressed in resting cells and must first be induced by certain cytokines,
      microbial products, or lipopolysaccharide. Since NO production has both
      beneficial and detrimental consequences, understanding the molecular mechanisms
      that regulate NOS expression is critical to the control of NO release in
      homeostatic and pathophysiologic conditions. The purpose of this review is to
      describe the molecular biology of NO synthases, with particular emphasis on the
      regulation of the human NO synthase genes. Transcriptional and post
      transcriptional regulation of neuronal and endothelial cNOS genes will be
      reviewed first, followed by the molecular regulation of the inducible NOS gene.

PMID- 9544421
TI  - Role of nitric oxide in genotoxicity: implication for carcinogenesis.
AB  - Reactive oxygen species can initiate carcinogenesis by virtue of their capacity
      to react with DNA and cause mutations. Recently, it has been suggested that
      nitric oxide (NO) and its derivatives produced in inflamed tissues could
      contribute to the carcinogenesis process. Genotoxicity of NO follows its reaction
      with oxygen and superoxide. It can be due either to direct DNA damage or indirect
      DNA damage. Direct damage includes DNA base deamination, peroxynitrite-induced
      adducts formation and single strand breaks in the DNA. Indirect damage is due to
      the interaction of NO reactive species with other molecules such as amines,
      thiols and lipids. The efficiency of one pathway or another might depend on the
      cellular antioxidant status or the presence of free metals.

PMID- 9544422
TI  - Role of nitric oxide in mediation of macrophage cytotoxicity and apoptosis.
AB  - Macrophages can recognize and eliminate tumor cells. To this effect, these cells
      use a variety of cytotoxic effectors. Recent work has paid particular attention
      to nitric oxide (NO) and its metabolic by-products in mediating macrophage tumor
      cytotoxicity. Moreover, work from this and other laboratories have indicated that
      macrophage-dependent, NO mediated tumor cell death meets the morphologic and
      molecular criteria that define apoptotic cell death. This review will initially
      discuss the characteristics of macrophage tumor cytotoxicity and the potential
      mechanisms by which NO can induce apoptosis in tumor cells. In addition,
      observations of spontaneous and acquired resistance to NO will be analyzed.
      Lastly, the relevance of results obtained using animal cells to the biology of
      the human macrophage will be considered.

PMID- 9544424
TI  - Role of nitric oxide in angiogenesis and microcirculation in tumors.
AB  - Nitric oxide (NO) is a free radical molecule with high reactivity, a short half
      life and a variety of physiological activities. The role of NO in tumor
      microcirculation, based on the data collected to date, can be summarized as
      follows: 1) NO may partially mediate tumor angiogenesis; 2) endogenous NO derived
      from tumor vascular endothelium and/or tumor cells increases and/or maintains
      tumor blood flow via dilatation of arteriolar vessels, decreases leukocyte
      endothelial interaction, and increases vascular permeability; 3) exogenous NO can
      increase tumor blood flow via vessel dilatation, and reduce vessel tone; and 4)
      NO production rates and vascular response to NO are heterogeneous and tumor
      dependent. Modulation of NO level in tumor vessels can alter tumor hemodynamics
      and thus augment oxygen, drug, gene vector and effector cell delivery to solid
      tumors.

PMID- 9544423
TI  - Therapy of cancer metastasis by activation of the inducible nitric oxide
      synthase.
AB  - The process of cancer metastasis consists of multiple sequential and highly
      selective steps. The vast majority of tumor cells that enter the circulation die
      rapidly; only a few survive to produce metastases. This survival is not random.
      Metastases are clonal in origin and are produced by specialized subpopulations of
      cells that preexist in a heterogeneous primary tumor. Experimental studies
      concluded that metastatic cells survive in the circulation whereas nonmetastatic
      cells do not. In part, this difference is due to an inverse correlation between
      expression of endogenous inducible nitric oxide synthase (iNOS) and production of
      nitric oxide (NO) and metastatic potential. Direct evidence for the role of iNOS
      in metastasis has been provided by our data on transfection of highly metastatic
      murine K-1735 clone 4 (C4.P) cells which express low levels of iNOS, with a
      functional iNOS (C4.L8), inactive mutated iNOS (C4.S2), or neomycin resistance
      (C4.Neo) genes in medium containing 3 mM of the specific iNOS inhibitor NG-L
      methyl arginine (NMA). C4.P, C4.Neo, and C4.S2 cells were highly metastatic,
      whereas C4.L8 cells were not. Moreover, C4.L8 cells produced slow-growing
      subcutaneous tumors in nude mice, whereas the other 3 cell lines produced fast
      growing tumors. In vitro studies indicated that the expression of iNOS in C4.L8.5
      cells was associated with either cytostasis or cytolysis via apoptosis, depending
      upon NO output. The tumor cells producing high levels of NO underwent
      autocytolysis and produced cytolysis of bystander cells under both in vitro and
      in vivo conditions. Multiple i.v. injections of liposomes containing a synthetic
      lipopeptide upregulated iNOS expression in murine M5076 reticulum sarcoma cells
      growing as hepatic metastases. The induction of iNOS was associated with the
      complete regression of the lesions. Transfection of interferon-beta suppressed
      tumor formation and eradicated metastases, which was apparently linked to iNOS
      expression and NO production in host cells such as macrophage. Besides mediating
      cell death, NO produced tumor suppression by regulating expression of genes
      related to metastasis, e.g., survival, invasion, and angiogenesis. Suppression of
      metastasis can be achieved through use of immunomodulators that induce iNOS
      expression in tumor lesions or by the direct delivery of the iNOS gene to tumor
      cells or host cells through liposome and/or viral vectors.

PMID- 9544425
TI  - Role of nitric oxide in tumor progression: lessons from experimental tumors.
AB  - Nitric oxide (NO), a potent biological mediator, plays a key role in
      physiological as well as pathological processes, including inflammation and
      cancer. The role of NO in tumor biology remains incompletely understood. While a
      few reports indicate that the presence of NO in tumor cells or their
      microenvironment is detrimental to tumor cell survival and consequently their
      metastatic ability, a large body of clinical and experimental data suggest a
      promoting role of NO in tumor progression and metastasis. We suggest that tumor
      cells capable of very high levels of NO production die in vivo, and those
      producing or exposed to lower levels of NO, or capable of resisting NO-mediated
      injury undergo a clonal selection because of their survival advantage; they also
      utilize certain NO-mediated mechanisms for promotion of growth, invasion and
      metastasis. The possible mechanism(s) are: (a) a stimulatory effect on tumor cell
      invasiveness, (b) a promotion of tumor angiogenesis and blood flow in the tumor
      neovasculature, and (c) a suppression of host anti-tumor defense. In this review,
      we discuss these mechanisms on the basis of data derived from experimental
      models, in particular, a mouse mammary tumor model in which the expression of
      eNOS by tumor cells is positively correlated with invasive and metastatic
      abilities. Tumor-derived NO was shown to promote tumor cell invasiveness and
      angiogenesis. The invasion-stimulating effects of NO were due to an upregulation
      of matrix metalloproteases and a downregulation of their natural inhibitors.
      Treatment of tumor-bearing mice with NO-blocking agents reduced the growth and
      vascularity of primary tumors and their spontaneous metastases. We propose that
      selected NO-blocking drugs may be useful in treating certain human cancers either
      as single agents or as a part of combination therapies.

PMID- 9544426
TI  - Role of nitric oxide in tumour progression: lessons from human tumours.
AB  - Varied cellular expression and localisation of nitric oxide synthase (NOS)
      isoforms has been shown in human cancers, including tumours of the breast, ovary,
      stomach, cervix and central nervous system. Mapping of NOS expression within
      tumour tissue from breast and gastric cancers shows inducible NOS (iNOS) is
      expressed predominantly in stromal (macrophage and endothelial) cells, although
      the level of NOS activity is at least 1-2 orders of magnitude lower than the
      enzyme activity associated with cytotoxicity and apoptosis. There is evidence
      that the intratumoural environment may provide chemoattractant signals for
      monocyte-macrophage recruitment and their subsequent activation via expression of
      interleukin-4, IgE, and CD23. Such signals lead to induction of iNOS in human
      macrophages in vitro. The correlation between NOS activity and grade for breast
      cancer suggests that NO may provide a positive growth signal within the tumour
      microenvironment. In vivo studies showing increased growth rate, vascular density
      and invasiveness of a human tumour cell line transfected to constitutively
      express iNOS support this. Furthermore, in vivo administration of a highly
      selective inhibitor of iNOS limited invasion and growth rate of iNOS transfected
      tumours and other murine tumours expressing this isoform. Inhibition of NO
      generation in the intratumoural microenvironment may prove a useful cancer
      therapy by preventing angiogenesis, invasion and metastasis.

PMID- 9544427
TI  - The role of nitric oxide in interleukin-2 therapy induced hypotension.
AB  - Nitric oxide is an uncharged free radical that mediates a range of physiologic
      processes in the vasculature. As a principal determinant of vascular tone, the
      overproduction of nitric oxide has been implicated in the pathogenesis of sepsis-
      and cytokine-induced hypotension. The enzyme that produces nitric oxide, nitric
      oxide synthase, exists in three isoforms. One of the three isoforms, inducible
      nitric oxide synthase, is expressed in many cell types only after stimulation by
      cytokines and/or endotoxin. Compared to the constitutive nitric oxide synthase
      enzymes, the inducible enzyme generates larger quantities of nitric oxide for
      longer periods. Expression of the inducible isoform in vitro requires stimulation
      by a mixture of cytokines including interferon-gamma, tumor necrosis factor
      alpha, and interleukin-1 beta. These proinflammatory cytokines are known
      mediators of sepsis and are also produced in the serum of cancer patients during
      interleukin-2 therapy, thereby leading to excessive production of nitric oxide.
      Interleukin-2 therapy is associated with a spectrum of cardiovascular toxicities
      and hemodynamic alterations that are indistinguishable from those seen in septic
      shock. Many of these hemodynamic effects have been linked to the overproduction
      of nitric oxide via a cytokine-inducible nitric oxide pathway. In this regard,
      inhibition of nitric oxide synthesis represents a novel approach to limit the
      cardiovascular toxicity associated with interleukin-2 therapy and to improve its
      therapeutic index. Clinical trials to evaluate the efficacy of nitric oxide
      synthase inhibitors in reversing the hypotension associated with IL-2 therapy are
      now underway.

PMID- 9544428
TI  - Role of nitric oxide in IL-2 therapy-induced capillary leak syndrome.
AB  - Nitric oxide (NO) is a potent short-lived and short range bioactive molecule,
      which plays a key role in physiological and pathological processes including
      inflammation and cancer. Detrimental effects of excessive NO production during
      septic shock have been well recognized. We tested the hypothesis that 'capillary
      leak syndrome' following systemic interleukin-2 (IL-2) therapy resulted from a
      cascade of events leading to the induction of NO which, directly or indirectly,
      injured capillaries and caused fluid leakage. Our results provided the first
      direct evidence that the induction of active NO synthase (NOS) leading to the
      overproduction of NO is instrumental in IL-2-induced capillary leakage in mice
      and that successful blocking of this overproduction with chronic oral
      administration of NOS inhibitors can mitigate this leakage without interfering
      with the beneficial antitumor effects of IL-2 therapy. NO blocking agents can, in
      fact, improve IL-2-induced antitumor effector cell activation, as well as tumor
      regression. In our studies, NO blocking agents alone reduced the growth and
      metastasis of a murine mammary carcinoma, at least in part, by mitigating the
      invasion and angiogenesis-stimulating role of tumor-derived NO. Thus, NOS
      inhibitors may be useful in treating certain tumors and serve as valuable
      adjuncts to systemic IL-2 based immunotherapy of cancer and infectious diseases.

PMID- 9544429
TI  - Evaluation of cell-mediated immunity and circulating immune complexes as
      prognostic indicators in cancer patients.
AB  - Cell-mediated immunity (CMI) and circulating immune complexes (CIC) were
      estimated in 55 cancer patients and 25 control volunteers to evaluate their
      prognostic significance. Cancer patients comprised head and neck cancer (11),
      breast cancer (13), gastrointestinal cancer (10), genitourinary cancer (11), and
      lymphomas and sarcomas (10). CMI was tested in vitro by early rosette-forming
      cells (ARFC) and total rosette-forming cell (TRFC) counts. ARFC count in control
      group was 758.1 +/- 78.09 cells/cumm. In advancing clinical stages of cancer (I
      IV), ARFC counts were decreased (i.e., 601.12 +/- 74.96 [p < 0.01]; 494.8 +/-
      71.83 [p < 0.001]; 432.44 +/- 36.05 [p < 0.001], and 438.55 +/- 69.99 [p < 0.001]
      cells/cumm, respectively). TRFC count in control group was 1029 +/- 88.39
      cells/cumm. In cancer stages I through IV, these counts decreased significantly
      (i.e., 699.63 +/- 66.24; 597.55 +/- 82.9; 505.11 +/- 52.56; and 501.55 +/- 69.99
      cells/cumm, respectively [p < 0.001]. Dinitrochlorobenzene cutaneous reactivity
      in vivo was 100% positive in control group, 62.5% positive in cancer stage I, 5%
      positive in stage II, and negative in stages III and IV. CIC of intermediate size
      were estimated by polyethylene glycol precipitation (PEG pptn) technique, which
      detects CIC in the ratio of 2:1 (Ag2Ab). Mean PEG index in control group was 39.5
      +/- 4.65; sequential increase in CIC was observed in advancing clinical stages of
      cancer (I-IV)(i.e., 49 +/- 7.03 [p < 0.01]; 75.38 +/- 44.01 [p < 0.001]; 93.38 +/
      44.57 [p < 0.001]; and 216.00 +/- 147.05 [p < 0.001], respectively). Latex
      agglutination inhibition (LAI) titer was done to detect CIC as small as 8s, which
      constitute the opposite polar end of CIC spectrum. LAI titers in control group
      were nil. However, LAI titers in cancer stages I through IV were 1 +/- 2.64; 8.6
      +/- 5.6 (p < 0.001); 12.00 +/- 8.11 (p < 0.001); and 25.77 +/- 9.06 (p < 0.001),
      respectively. Decrease in CMI and subsequent increase in CIC indicate unfavorable
      prognosis in cancer patients, and also precede clinical manifestation of
      increased tumor mass in vivo.

PMID- 9544430
TI  - Risk factors for glioma in adults: a case-control study in northeast China.
AB  - A case-control study of risk factors for glioma in adults was carried out in
      Heilongjiang province in northeast China. Between September 1989 and May 1995,
      218 histologically confirmed cases of glioma requiring surgery for tumor removal
      (139 astrocytoma glioma and 79 other glioma) and 436 controls with non-neoplastic
      and non-neurological disease were recruited and personally interviewed in the
      wards of six major hospitals. Controls were matched by sex, age, and area of
      residence. Occupational, lifestyle, and medical information was obtained through
      a standardized questionnaire. Use of liquor was associated with cancer risk.
      Compared with males who never drank liquor, males with total lifetime liquor
      consumption of less than 1000 liters had an adjusted odds ratio (OR) of 1.60 (95%
      CI: 0.89-2.88) and for more than 1000 liters, 2.73 (95% CI: 1.06-7.08).
      Statistically significant associations were also found for diseases related to
      the brain (OR: 5.75; 95% CI: 1.08-30.47) and trauma to the head requiring medical
      attention (OR: 4.09; 95% CI: 2.51-10.31). Increased consumption of vegetables and
      of fruit were each associated with decreased glioma risk. Compared with lowest
      quartile intake, adjusted risks associated with highest quartile intake were 0.51
      (95% CI: 0.29-0.89) for total vegetables and 0.28 (95% CI: 0.16-0.51) for total
      fruit.

PMID- 9544431
TI  - Cigarette smoking and cervical dysplasia among non-Hispanic black women.
AB  - This is the first case-control study to determine whether smoking is associated
      with cervical dysplasia, after adjustment for human papillomavirus (HPV)
      infection, among a group of non-Hispanic black women. Subjects were interviewed
      and asked questions about smoking and other risk factors for cervical cancer. HPV
      infection was determined by hybrid capture. Thirty-two women with histologically
      confirmed incident dysplasia and 113 control women with normal cytologic smears
      were enrolled; all women were HIV negative. Smoking was more strongly associated
      with dysplasia among women with high-grade lesions than among all case women
      combined. After adjustment, women with high-grade lesions were roughly four times
      more likely to be ever (odds ratio [OR]: 3.8; 95% confidence interval [CI]: 0.76
      18.4) or current (OR: 4.3; 95% CI: 0.83-21.9) smokers, compared with control
      women. Larger studies among black women that control for HPV infection are needed
      to confirm these findings and to explore associations among black women with low
      grade lesions.

PMID- 9544432
TI  - Immunohistochemical prediction of radiation response and local control in
      radiation therapy for cervical cancer.
AB  - Prognosis of 64 cervical cancer patients treated with radiation therapy was
      analyzed by tumor expressions of c-erbB-2 oncoprotein (CerbB-OPE) and p53 protein
      (p53-PE), Ki-67 growth fraction (Ki-GF), and the mitotic index of proliferating
      cell population (pMI). Positivity of CerbB-OPE and p53-PE was 42.4% and 84.6%,
      respectively. Mean Ki-GF and pMI were 33.0% and 2.7%, respectively. Mean Ki-GF
      for CerbB-OPE was 38.3%, significantly higher than the 26.2% for the negative
      patients (p < 0.01). The mean pMI for CerbB-OPE was 2.00%, significantly lower
      than the 3.70% of the negative patients (p < 0.05). The 5-year survival rate of
      CerbB-OPE-positive patients was 44.4%, significantly lower than the 74.8% of
      negative patients (p < 0.01). The survival rates of Ki-GF < 33% was 44.7%,
      significantly lower than the 87.5% of Ki-GF > or = 33% (p < 0.01). The survival
      rates of pMI > or = 3.5% was 0%, significantly lower than the 81.8% of pMI < 3.5%
      (p < 0.001). The survival rates of p53-PE-positive and negative patients were
      52.8% and 85.0%, respectively (p > 0.1). The poor prognosis of the cervical
      cancer with CerbB-OPE, lower Ki-GF, and higher pMI were due to local recurrence
      following radiation therapy. Multiple regression analysis indicated that pMI was
      the strongest prognostic factor and was followed by CerbB-OPE, tumor volume, and
      Ki-GF. In conclusion, the c-erbB-2 oncoprotein expression, Ki-67 growth fraction,
      and the mitotic index of proliferating cell population were considered to be
      effective prognostic factors in radiation therapy for cervical cancer.

PMID- 9544433
TI  - GSTM1 and GSTT1 genes are potential risk modifiers for bladder cancer.
AB  - The role of the polymorphic glutathione S-transferase genes GSTM1 and GSTT1 in
      the development and in the clinicopathological outcome of bladder cancer was
      investigated in 37 Egyptian bladder cancer patients and 34 matched controls. Of
      the 37 patients studied, 26 had transitional cell carcinoma (TCC) and 11 had
      squamous cell carcinoma (SCC). Fourteen out of twenty-six TCC and four out of
      eleven SCC patients were infected with schistosoma. We observed an increased
      relative risk for bladder cancer associated with the GSTM1 null genotype (OR =
      2.99; 95% CL = 1.01-9.00; p = 0.02). The relative risk was more pronounced in
      squamous cell carcinoma (SCC) (OR = 5.70; 95% CL = 0.91-36.70; p = 0.03) than in
      transitional cell carcinoma (TCC) (OR = 2.39; 95% CL = 0.73-7.90; p = 0.08). Our
      results also indicate that the GSTT1 polymorphism is individually associated with
      increased risk for bladder cancer (OR = 4.93; 95% CL = 1.39-18.42; p = 0.004)
      with no preferential increase in risk with respect to the type of the carcinoma.
      Individuals with the null genotype for both GSTM1 and GSTT1 were at a
      significantly higher risk for developing bladder cancer than individuals with
      both genes present (OR = 9.92; 95% CL = 1.84-46.90; p = 0.001). These individuals
      were more susceptible to developing SCC than TCC (OR = 14.16; 95% CL = 1.35
      131.35; p = 0.01; and OR = 8.5; 95% CL = 1.38-60.10; p = 0.007, respectively). In
      conclusion, our results indicate that the null genotypes for GSTM1 and GSTT1,
      either individually or in combination, are important host risk factors for
      bladder cancer. In addition, the null GSTM1 genotype may also affect the
      clinicopathological tumor outcome. Since the deleted genotypes for GSTM1 and
      GSTT1 are prevalent in the general population, the identification of these
      individuals may provide a useful public health approach for early detection and
      prevention of environmental cancers.

PMID- 9544434
TI  - Prognostic significance of c-erbB-2 gene expression in the poorly differentiated
      type of adenocarcinoma of the stomach.
AB  - Prognostic significance of c-erbB-2 gene abnormalities is unclear in the poorly
      differentiated type of gastric carcinoma, because the abnormalities of this gene
      have been reported to be restricted to the differentiated type of gastric
      carcinoma. In this study, correlation of c-erbB-2 gene
      amplification/overexpression of mRNA and protein were studied in the poorly
      differentiated type of gastric carcinoma. c-erbB-2 gene amplification determined
      by the slot-blot hybridization was observed in 11 (13%) of 82 gastric cancer, and
      8 of 11 tumors were poorly differentiated. In addition, c-erbB-2 mRNA expression
      was studied by the reverse transcriptase-polymerase chain reaction. Four (17%) of
      24 tumors showed overexpression of c-erbB-2 mRNA, and all these four exhibited
      morphologically a poorly differentiated type. Among 157 poorly differentiated
      gastric cancers, 20 (13%) tumors showed immunohistochemically c-erbB-2 protein
      expression. These tumors had significantly higher incidences of larger tumor,
      serosal invasion-positive tumors, node-positive tumor, or peritoneal
      dissemination-positive tumor than those without c-erbB-2 expression. Furthermore,
      patients with c-erbB-2 protein overexpression ran poorer prognoses than those
      without c-erbB-2 expression. From these results, we conclude that expression c
      erbB-2 tissue status may be a good prognostic indicator in poorly differentiated
      gastric carcinoma.

PMID- 9544435
TI  - Shared tumor antigens in colorectal carcinoma and neuroendocrine tumors.
AB  - ND4 monoclonal antibody recognizes a tumor marker found on poorly differentiated
      colorectal cancer. We demonstrate its expression in 25% of gastrointestinal
      neuroendocrine tumors, which also express CEA in 37% of cases. As in colorectal
      cancer the ND4 marker is predominantly membrane bound in a colonic neuroendocrine
      tumor cell line, LCC-18 (p < 0.05). The ND4 marker is absent in a poorly
      differentiated colorectal cancer cell line that does not express CEA or other
      tumor antigens. Shed antigen in the serum of patients with neuroendocrine tumors
      is detected in only five of seven patients with the carcinoid syndrome and two of
      four of those without evidence of the syndrome. However, the reactivity was less
      in the patients with localized disease, and this test is unlikely to be of
      diagnostic utility in this group of patients. The sharing of this antigen in
      colorectal cancer and neuroendocrine tumors is not universal, but does support
      the common-cell progenitor theory for the origin of these tumors.

PMID- 9544436
TI  - Effects of gamma-glutamylcysteine ethyl ester in cisplatin-induced changes in
      prostanoid concentrations in rat gastric and colonic mucosa.
AB  - We evaluated changes in gastric and colonic mucosal prostanoid contents in rats
      treated with cisplatin. We also determined effects of gamma-glutamylcysteine
      ethyl ester (GCE), a pro-drug of glutathione, on cisplatin-induced changes in
      prostanoid concentrations. Rats were divided into three groups--the control: 0.5
      ml of physiological saline was administered intraperitoneally (i.p.); the
      cisplatin group: 0.5 ml of cisplatin, 10 mg/kg, was administered i.p.; the GCE +
      cisplatin group: GCE, 30 min before cisplatin injection. In each group, rat
      gastric and colonic mucosa were isolated and their prostanoid concentrations were
      determined using high-performance liquid chromatography. 6-Keto-PGF1 alpha, PGF2
      alpha, PGE2 were detected in gastric mucosa. In addition to these prostaglandins
      (PGs), thromboxane (TX) B2 was also detected in the colonic mucosa. In the
      cisplatin group, gastric mucosal 6-keto-PGF1 alpha concentration decreased
      significantly 24 h after administration, while PGE2 and PGD2 concentrations were
      increased significantly after 12 and 24 h, respectively. In colonic mucosa,
      cisplatin increased PGE2 and PGD2 concentrations, while it decreased TXB2
      concentration. 6-Keto-PGF1 alpha concentration was not affected by cisplatin in
      colonic mucosa. GCE canceled out these changes in prostanoid concentrations in
      both gastric and colonic mucosa. Changes in prostanoid concentrations might be
      implicated in the adverse gastrointestinal effects of cisplatin, and clinical
      application of GCE could be expected.

PMID- 9544437
TI  - Screening mammography behavior after a false positive mammogram.
AB  - This pilot study describes women's interpretations of the experience of a false
      positive mammogram followed by a negative biopsy and the impact of this
      experience on subsequent participation in screening mammography. A 25-min, open
      ended telephone interview was administered in 1992 to 30 women over age 39 who
      had negative biopsies in 1987 preceded by abnormal mammograms. Almost twice as
      many women reported getting regular mammograms after the biopsy (60%) as did
      before 1987 (33%). Most received their next mammogram after the biopsy within the
      recommended interval (73%), and those getting regular mammograms prior to the
      biopsy experience were more likely than those who did not have a prior habit of
      undergoing mammography to continue to get them afterwards. These preliminary
      findings suggest that a negative breast biopsy after a positive mammogram does
      not reduce a patient's likelihood of undergoing screening in the future. In fact,
      it may serve as an impetus for increased compliance with screening
      recommendations.

PMID- 9544439
TI  - Resistance of spontaneously transformed Syrian hamster embryo cells and their
      malignant variants to cytotoxic activity of recombinant tumor necrosis factor
      alpha.
AB  - To study the possible role of the host macrophages in the selection of tumor
      cells and tumor progression, a series of Syrian hamster tumor cell lines all
      originating from a single spontaneously transformed Syrian hamster embryo cell
      line (STHE strain) have been established. These STHE tumor cell variants,
      selected either in vitro with resident and lipopolysaccharide-activated
      macrophages or in vivo, differ in tumorigenic and metastatic activity. The
      selected malignant STHE cells become resistant to cytotoxic activity of activated
      peritoneal macrophages and of exogenous hydrogen peroxide (H2O2). Since activated
      macrophages are a known source for both cytotoxic agents H2O2 and tumor necrosis
      factor (TNF), the purpose of the present study was to define the sensitivity of
      the STHE tumor cell lines to a direct cytotoxic activity mediated by recombinant
      TNF-alpha in an attempt to understand the role of the cytokine in in vitro
      selection of a malignant STHE cells by activated macrophages. The spontaneously
      transformed STHE cells (selected in vivo and in vitro) as well as the hamster
      embryo cells transformed in vitro by a tumorigenic Rous sarcoma virus (Schmidt
      Ruppin strain) were used as targets. TNF-alpha-sensitive mouse L929 cells were
      included in the study as a positive control. Sensitivity of actinomycin D
      pretreated target cells studied for cytotoxic activity of a recombinant TNF-alpha
      was examined over 21 h with a crystal violet dye assay. It was found that, in
      contrast to L929 cells, the spontaneously transformed STHE cells as well as
      tumorigenic Rous sarcoma virus hamster embryo transformants, were all
      significantly resistant to the TNF-alpha-mediated cytolysis. This indicates that
      TNF-alpha is not the single factor responsible in in vitro selection of malignant
      STHE cell variants by activated macrophages. It appears that H2O2 is involved in
      the selection of the hamster macrophage-resistant STHE tumor cells.

PMID- 9544438
TI  - Enhancement of tumor cell lysis by natural killer cells after blocking of HLA
      monomorphic determinant using F(ab')2 fragment of W6/32.
AB  - It has been known that negative signal of natural killer (NK) cells is triggered
      by HLA-polymorphic determinant (PMD) of target cells. However, it is not clear
      whether or not the negative signal is triggered by HLA-monomorphic determinant
      (MMD). In this study, we determined the interaction of NK receptor and MMD by
      mean of a blocking test. For the blocking, W6/32, which is an antibody to the
      MMD, was used. As target cells, we used a tumor cell line H42 and several cell
      lines. The H42 was established from a bladder cancer patient after radiation
      therapy. This cell line was demonstrated to be PMD negative but MMD positive and
      showed NK sensitivity. We had established one more cell line, H41, from the same
      patient before the radiation therapy. However, the H41 possessed both the PMD and
      MMD and exhibited NK resistance. Thus, the NK sensitivity of the H42 may be due
      to depression of the PMD. We performed a blocking test against the MMD of these
      cell lines. When the H42 was pretreated with F(ab')2 fragment of the W6/32, the
      killing by NK cells increased. Other cell lines, EB33, KMT-1, and HMy2-C1R, which
      possessed low levels of PMD, were killed moderately after the pretreatment,
      although the H41 and other cell lines (KO, MT-2, OKM-3T), which possessed high
      levels of PMD, were killed only slightly. These findings suggest that the
      negative signal may be triggered not only by the PMD but also by the MMD.

PMID- 9544440
TI  - Families' experiences of caring at home for a technology-dependent child: a
      review of the literature.
AB  - Recent medical advances have led to the emergence of a group of chronically ill
      children who are dependent upon technology for their survival. Many of these
      children are cared for at home by their parents. This paper presents an overview
      of the literature that has examined the experiences of families caring for a
      technology-dependent child at home. The social, emotional and financial impact on
      families and their perspectives on the services supporting them at home is
      described. The paper concludes by identifying areas where further research is
      needed.

PMID- 9544441
TI  - Emotional and behavioural difficulties in children with diabetes: a controlled
      comparison with siblings and peers.
AB  - This study describes a comparison of children with insulin dependent diabetes
      mellitus (IDDM) with two control groups: the sibling nearest to them in age, and
      peers matched for gender and age. A broad range of emotional and behavioural
      difficulties were assessed using the Conners' Teachers' and Parents' rating
      scales (CTRS 39 and CPRS 93). Individually completed children's questionnaires
      provided qualitative data about the children's problems. The results of the study
      showed markedly higher scores for the children with diabetes on the parent scales
      on factors such as hyperactivity, psychosomatic and restless/disorganized, in
      comparison to their siblings, but not their peers. These differences were not
      found on the Teachers' Scales. The findings are discussed in terms of parental
      perceptions of children with diabetes and the difficulties these children and
      their siblings experience in their lives. Suggestions are made for further
      research.

PMID- 9544442
TI  - The British Paediatric Surveillance Unit--a pioneering method for investigating
      the less common disorders of childhood. Report of a seminar held in June 1995.
AB  - The British Paediatric Surveillance Unit (BPSU) of the Royal College of
      Paediatrics and Child Health is an 'active' case reporting scheme set up in 1986
      to facilitate the investigation of uncommon childhood conditions of public health
      and clinical importance in the UK and Ireland. Its methodology involves the
      monthly mailing of a card containing a menu of up to 12 reportable conditions to
      all clinically active paediatricians in the British Isles. Respondents either
      indicate any cases seen in the past month or make a nil return. The BPSU forwards
      details of respondents reporting cases to the investigators, who when obtain
      information from the clinician. The menu changes from time to time and studies
      undergo a rigorous selection process. In 1995, the BPSU held an international
      seminar to review lessons learned during its first decade which would improve and
      develop surveillance of paediatric disorders. Over the 9 years to mid-1995 a
      total of 34 studies took place (25 completed, nine still in progress) with a high
      respondent response rate (e.g. 90% in 1994). Underascertainment had been
      addressed by seeking, in parallel, other sources of cases, e.g. death
      registrations, laboratory reports, other relevant clinical specialists, and by
      use of capture-recapture techniques. Other specialties and countries have since
      followed the BPSU example providing opportunity for multispeciality and
      international studies. The latter were valuable, but required careful planning to
      standardize case definitions and laboratory techniques, otherwise geographical
      differences in the incidence of study disorders were difficult to interpret. The
      BPSU has facilitated studies which increased knowledge about a range of disorders
      and informed national policy decisions. It also increased diagnostic awareness
      and showed itself able to respond to public health emergencies. Its emulation in
      further countries will have similar benefits.

PMID- 9544444
TI  - Do the younger siblings of learning-disabled children see them as similar or
      different?
AB  - Pre-school siblings' comments about, and behaviour towards, their older, learning
      disabled brothers and sisters are reported. Initially, some of the very young
      siblings want to be similar, and attempt to imitate their brothers and sisters,
      particularly if he or she is also physically disabled; this may be because of the
      immediate visibility of physical disability, which makes it appear interesting
      and important to the younger child. Before they are 2 years old, children are
      able to recognize that their older brothers and sisters are different, and often
      imitate the parents' behaviour towards the older child.

PMID- 9544443
TI  - Short stature at school entry--an index of social deprivation? (The Wessex Growth
      Study).
AB  - This study was carried out to examine the biological and environmental variables
      associated with non-organic short stature. We observed an unselected population
      of very short normal children (SN) and their age- and sex-matched controls (C)
      within the community. All 14,346 children in two health districts entering school
      during 2 consecutive years were screened for short stature, and those whose
      height lay below the 3rd centile, according to Tanner and Whitehouse standards (n
      = 180) were identified. Excluding 32 with pathology, five from ethnic minorities
      and three who refused to take part, the remaining SN children (mean height SDS
      2.26) were matched with 140 age- and sex-matched controls (C) of average height
      (mean height SDs 0.14). Birth weight, target height and predicted adult height
      (based on parental height and bone age respectively), medical and social
      background (obtained from parental interviews), and school performance (assessed
      by class teachers) were the main outcome measures. Mean birth weight of the SN
      children was significantly lower than C (SN = 2845 g, C = 3337 g, P < 0.001).
      Mean mid-parental target height was also very different (SN = 162.0 cm, C = 170.9
      cm, P < 0.001). Thirty-five per cent of SN children (C = 6%) had height SD scores
      below parental target range, though only 10% had predicted heights below target
      range (mean delay in bone age 0.68 years). There was a significant difference
      between SN children and C in the number of children in the household (SN = 2.8, C
      = 2.4 (P = 0.007) and in socio-economic status (P < 0.002). Many more SN children
      were in social classes IV and V (SN = 31%, C = 13%, P < 0.002), and had an
      unemployed father (SN = 22%, C = 10%, P < 0.010), highlighting the importance of
      environmental influences on growth. One in four SN children was judged to have
      serious psychosocial problems. However, the lower the socio-economic class, the
      less likely the SN children were to be inappropriately short for parents.
      Significantly more SN children were reported to have asthma (SN = 18%, C = 7%, P
      < 0.007) and eczema (SN = 19%, C = 5%, P < 0.001), though only the latter was
      significantly associated with stature below target height for both SN and C
      groups. Biological variables are often insufficient to explain short stature. No
      child, whatever the parental height, should be dismissed as normal without
      careful evaluation, as poor growth in the early years may be an important pointer
      to an adverse but potentially remediable environment.

PMID- 9544445
TI  - An activity week for children with cancer: who wants to go and why?
AB  - Many children now live with cancer rather than die from it, and such children
      need both to continue their social, emotional and cognitive development and to
      make long-term psychological adjustments. This paper presents the findings of a
      research project set up to explore issues pertinent to the current provision of
      an activity week experience for a group of British paediatric cancer patients.
      The aims of the study included finding out which factors discriminate between
      families who apply for a place to attend the week for their child and families
      who do not, and to develop a knowledge of what factors are considered by parents
      and children. The findings suggest that the week appeals to children who are
      confident, active and able to separate from parents and whose parents are keen to
      encourage independence and new experiences. Children diagnosed and treated at a
      younger age and further away from treatment were more likely to express concerns
      about being homesick and safety and to not apply for the week. Issues of
      protection, independence and disability are discussed with reference to the
      importance of parental attitude on children's psychological accommodation to
      disease and treatment and to the experiences of adult survivors of childhood
      cancer.

PMID- 9544446
TI  - Alzheimer's amyloid beta interaction with normal human plasma high density
      lipoprotein: association with apolipoprotein and lipids.
AB  - We report studies of the interaction of Alzheimer's amyloid beta protein (A beta)
      with normal human plasma high density lipoprotein (HDL), aiming to clarify to
      which lipoprotein (LP) structural constituent (apolipoprotein or lipid) soluble A
      beta is primarily bound. Purified HDLs were incubated with biotinylated A beta 1
      40 followed by LP repurification by size exclusion (SE) HPLC. SDS-PAGE,
      immunoblot and N-terminal sequence analysis of the biotin-A beta positive protein
      bands revealed that A beta is bound to many apolipoproteins of the HDL, mainly
      apoA-I, apoA-II, apoE and apoJ. On the other hand, reconstituted, protein-free
      HDL lipid particles also bind A beta peptide and inhibit its aggregation, as
      intact HDL does. This was assessed by SE-HPLC, SDS-PAGE, immunoblot analysis,
      ultrastructural electron microscopy and Congo Red staining for beta amyloid
      fibrils. Our data imply that A beta binding to lipids may play an important role
      in maintaining the peptide in solution and thus be particularly relevant to A
      beta normal and pathologic biochemistry and physiology.

PMID- 9544447
TI  - A routine method for the simultaneous measurement of retinol, alpha-tocopherol
      and five carotenoids in human plasma by reverse phase HPLC.
AB  - We describe a simple isocratic HPLC method for the accurate and precise
      measurement of retinol, alpha-tocopherol and the major carotenoids in plasma
      using UV detection. Reference ranges for retinol, alpha-tocopherol and five
      carotenoids are determined in a healthy population group. The most abundant
      carotenoids found in plasma were beta-carotene, lycopene, lutein and
      cryptoxanthin. Retinol, alpha-tocopherol and carotenoids were determined
      simultaneously using two internal standards, retinol acetate for retinol and
      tocopherol acetate for alpha-tocopherol and carotenoids. The use of echinenone as
      an internal standard for carotenoids was investigated. The protective effect of
      an antioxidant (ascorbic acid) on the stability of samples and extracted material
      is documented. The method is useful for the routine measurement of plasma
      retinol, alpha-tocopherol and carotenoids and could also be used in large scale
      epidemiological studies.

PMID- 9544448
TI  - An ultrasensitive, nonisotopic immunoassay for hyaluronan using the streptavidin
      biotin system.
AB  - A time-resolved fluoroimmunoassay for measuring hyaluronan concentrations in
      plasma and several biological fluids is described. The solid-phase immunoassay is
      based on the competition between aggregation of hyaluronan with the cartilage
      proteoglycan monomer, followed by binding of a monoclonal antibody to keratan
      sulfate of the proteoglycan and a biotinylated anti-mouse IgG. Fluorescence can
      be measured by a time-resolved fluorometer after binding of Eu(3+)-labelled
      streptavidin to the biotinylated IgG. The assay is precise and correlates well (r
      = 0.986) with the only established radioimmunoassay known. The results show that
      it is essential to perform a blank run without addition of proteoglycan, as
      endogenous proteoglycan disturbs the measurement and causes underestimation of
      plasma hyaluronan. The distinguishing feature of this assay is its extreme
      sensitivity (< 0.24 microgram/l of plasma). The mean analytical recovery after
      serial dilutions and addition was 100.3 and 101.3%, the within-assay and between
      assay coefficients of variation were 3.67% and 7.02%, respectively.

PMID- 9544449
TI  - Oxidation of erythrocyte glutathione by monocytes stimulated with interleukin-6.
      Analysis by 1H spin echo NMR.
AB  - 1H spin echo NMR was used to follow the release of reactive oxygen species (ROS)
      from human monocytes by monitoring erythrocyte glutathione status, which is
      sensitive to applied oxidative stress. This allowed the ability of the cytokine
      interleukin-6 (IL-6) to stimulate release of ROS from monocytes to be assessed in
      terms of oxidative damage to other cells, providing an estimation of its
      importance in vivo. It was found that incubation of monocytes with erythrocytes
      in the presence of IL-6 resulted in oxidation of the erythrocyte glutathione
      pool, indicating that oxidants are released in sufficient amounts to cause
      oxidative stress. High levels of IL-6 occurring in plasma of women with severe
      pre-eclampsia could therefore be responsible for depleted plasma antioxidants and
      haemolysis. The oxidation of erythrocyte glutathione was inhibited by the
      presence of the cyclooxygenase inhibitor indomethacin, suggesting that this may
      be of value in the treatment of oxidative pathologies.

PMID- 9544450
TI  - Elimination of alkaline phosphatases from circulation by the galactose receptor.
      Different isoforms are cleared at various rates.
AB  - Three isoforms of human alkaline phosphatase (liver, bone and placental ALP) were
      purified and their elimination studied after intravenous injection in rats. The
      rates of elimination were significantly inhibited by prior injection of
      asialofetuin, indicating that the uptake was mediated by the galactose receptor
      in liver. Their relative clearance rates differed, being rapid for the bone ALP,
      significantly slower for the liver isoform and very slow for the placental ALP.
      The bone ALP showed a rapid initial clearance, apparently related to its large
      glycan heterogeneity and to the presence of molecules with a low sialic acid
      content. When isolated from serum the liver and bone ALP isoforms showed
      clearance rates differing slightly from those of the organ derived forms. We
      conclude that differences in carbohydrate structure and amount of sialic acid of
      the three isoforms result in various clearance rates. These differences will also
      affect their serum concentrations as well as the composition and heterogeneity of
      the individual isoforms in serum.

PMID- 9544451
TI  - Erythrocyte membrane lipids and serum selenium in post-viral and alcoholic
      cirrhosis.
AB  - Erythrocyte-membrane fatty acid composition and cholesterol content were
      evaluated along with serum selenium in 33 patients with liver cirrhosis and in 40
      normal subjects. Thirteen patients were suffering from post-viral (group V) and
      20 from alcoholic (group A) cirrhosis. The aim of the study was to elucidate
      whether membrane lipid abnormalities in cirrhosis were linked to the aetiology of
      the disease or whether they were the results of the cirrhotic process itself. The
      patients presented a significant increase in membrane cholesterol, palmitic acid
      (C16:0) and saturated fatty acids (SFA), and a decrease in polyunsaturated fatty
      acids (PUFA) and polyunsaturated/saturated fatty acids ratio (P/S) compared with
      the control group. Serum selenium levels were significantly reduced. When
      patients were subdivided according to aetiology, the alcoholic patients showed
      greater lipid composition abnormalities than the viral cirrhotics (higher levels
      of SFA and lower PUFA and P/S), while pathologic palmitic acid, membrane
      cholesterol and serum selenium values were confirmed in both groups of patients.
      In conclusion, low serum selenium and a series of erythrocytes membrane lipid
      composition abnormalities would appear to be features peculiar to cirrhosis.
      Alcoholic cirrhotics, on the other hand, show a more deranged erythrocyte
      membrane lipid profile.

PMID- 9544452
TI  - Specific interaction of food proteins with apical membranes of the human
      intestinal cell lines Caco-2 and T84.
AB  - A comparison between the intestinal epithelial cell lines Caco-2 and T84 was made
      to assess the influence of enterocytic differentiation on food protein binding
      capacities of the brush border membrane. Cell morphology and expression of brush
      border-associated enzymes were studied as differentiation markers. Food protein
      binding to isolated brush border membranes was measured with a dot blot
      chemiluminescence assay. Early at confluence, Caco-2 cells exhibited a more
      differentiated state compared to T84 cells. Brush border membranes of both cell
      lines bound gliadin peptides, beta-lactoglobulin and ovalbumin specifically.
      Binding capacities increased from gliadin peptides to ovalbumin to beta
      lactoglobulin. There was correlation of membrane binding capacity with degree of
      cell differentiation. Due to their similarity to small intestinal epithelial
      cells, the colon carcinoma cell lines Caco-2 and T84 represent models for
      studying food protein-enterocytic brush border membrane interactions in relation
      to varying degrees of cell differentiation.

PMID- 9544453
TI  - Identification and quantitative analysis of haptoglobin Johnson heterozygote.

PMID- 9544454
TI  - The advantage of phenylalanine to tyrosine ratio for the early detection of
      phenylketonuria.

PMID- 9544455
TI  - Clinical specificity of a second-generation cardiac troponin T assay in patients
      with chronic renal failure.

PMID- 9544456
TI  - Stability of semicarbazide-sensitive amine oxidase in human blood and plasma.

PMID- 9544457
TI  - Genetic variation in human serum albumin: a 313 Lys-->Asn mutation in albumin
      reading identified by PCR analysis.
AB  - An early case of bisalbuminaemia was reported in this journal in 1964, with the
      name Albumin Reading added later. Its use in electrophoretic comparisons led to
      some new variants being described as 'of the Reading type' on this basis alone.
      Protein sequencing and DNA studies have since found the single point mutation 313
      Lys-->Asn common to this type, but the eponymous variant has not, until recently,
      been available for study. We now report on its characterisation using PCR
      analysis with allele-specific oligonucleotide primers, a method also applicable
      to studies of the population distribution of variants. We also draw attention to
      the need to link clinically-significant effects to individual variants of known
      structure.

PMID- 9544458
TI  - [Measles outbreaks in the Bern canton].
AB  - Currently, overall vaccination coverage against measles among infants ranges
      between 77% and 89% in Switzerland. Experience in other countries has shown that
      this level of vaccination is not sufficient to prevent measles outbreaks,
      especially among schoolchildren. During 1992 surveillance for measles outbreaks
      in closed populations was conducted in the Canton of Berne. Outbreaks were
      investigated for vaccine efficacy. Two measles outbreaks in schoolchildren were
      observed during the study period. In 2 Bernese suburban schools 6 measles cases
      in children (median age 12.5 years) occurred over a period of 37 days. One of the
      cases had been vaccinated. Vaccination rate in the healthy control children was
      89.7%. Estimated vaccine efficacy was 97.7% (95% confidence interval [CI]: 68%,
      99%). The second outbreak occurred in a rural region and comprised 21 measles
      cases (median age 7.5 years) within 43 days. 10 (47.6%) of the cases attended the
      same school. None of the cases had been vaccinated. Of the healthy control
      children 82.6% had received measles vaccine. Estimated vaccine efficacy was 100%
      (CI: 87%, 100%). These two measles outbreaks were due to failure to vaccinate
      rather than low vaccine efficacy. Surveillance for measles cases is currently not
      sufficient for the detection of measles outbreaks in our population. Laboratory
      confirmation of measles, especially in vaccinated persons, has become more
      important in a time of relatively low measles incidence.

PMID- 9544459
TI  - Extreme hypercapnia is not a long-term prognostic factor after near-fatal asthma:
      a 12-year follow-up study.
AB  - QUESTION OF THE STUDY: Some patients experiencing near-fatal asthma present with
      extreme hypercapnia (PaCO2 > or = 100 mm Hg), whereas others do not. The
      influence of this factor on short- and long-term outcome and quality of life in
      these patients is still unknown. PATIENTS AND METHODS: A series of 39 consecutive
      patients who had had an episode of near-fatal asthma between 1978 and 1992 were
      followed up. Long-term outcome and quality of life of the 12 patients who had
      experienced extreme hypercapnia were compared with those of the 27 patients who
      had not. RESULTS: Four patients died, but only 1 from asthma. Three patients were
      lost to follow-up. The remaining 32 patients had a median observation period of
      12.7 years. The hypercapnic patients did not significantly differ from the others
      in past asthma history, subsequent hospitalizations, medication needs, pulmonary
      function tests, quality of life and impairment/disability. In the event of
      subsequent near-fatal asthma attacks, they tended to present with hypercapnia
      levels similar to those observed during the first episode. DISCUSSION: Extreme
      hypercapnia in near-fatal asthma tended to recur, but is not an aggravating long
      term prognostic factor. Targeted surveillance of these high-risk patients should
      make it possible to reduce relapses and death rates from asthma.

PMID- 9544460
TI  - [Castleman disease: 2 unusual cases].
AB  - Castleman's disease is a localized, rare and benign hyperplasia of the lymph
      nodes, occurring mainly in the mediastinum. Three histologic types-
      hyalinvascular, plasmacellular and intermediate--have been recognized. We report
      on two patients with unusual locations of the disease, i.e. the pelvis and the
      retroperitoneum respectively. These observations show that diagnosis is
      difficult. They also indicate that, in selected patients, radiotherapy may induce
      tumor regression and allow the resection of apparently inoperable lesions.

PMID- 9544461
TI  - [Inflammatory mechanisms in the kidney].
AB  - Diverse mechanisms regulate the infiltration of the kidney with leukocytes in
      immune-mediated renal diseases. Chemotactic factors (chemokines) and
      intercellular adhesion molecules are known to promote the anchoring of
      infiltrating mononuclear cells in the kidney. We have recently shown that
      fragments of the polysaccharide hyaluronan (HA), but not native high molecular
      weight HA can cause prominent upregulation of the adhesion molecules ICAM-1 and
      VCAM-1 in renal proximal tubular cells. HA is also capable of stimulating the
      synthesis of chemokines in these cells. HA accumulates in many inflammatory renal
      diseases and could cause a proinflammatory effect by promoting leukocyte
      infiltration in the kidney after binding with its cellular receptor CD44. This
      mechanism may play an important role in immune renal injury in various renal
      diseases.

PMID- 9544462
TI  - [Phlebitis after vinorelbine].

PMID- 9544463
TI  - Risk equalization, competition and choice in Germany: a reply to Wysong and Abel.

PMID- 9544464
TI  - Competition and "cream skimming" in Germany: incentives and opportunities.

PMID- 9544465
TI  - Competition under a regime of imperfect risk adjustment: the Swiss experience.

PMID- 9544466
TI  - [Asylum seekers and refugees: health management of a complex minority].

PMID- 9544467
TI  - [Asylum seekers and refugees in general practice: problems and possible
      developments].
AB  - Health and health services provided to asylum seekers and refugees by the Swiss
      National Health System have so far not been systematically investigated. The aim
      of this cross-sectional study was to describe the attending asylum seekers and
      refugees demographically and clinically, to identify main problem areas as
      perceived by general practitioners and to highlight options and venues for
      improvements. 272 questionnaires have been filled in by GPs of eight "federal
      districts" (Kantone) and the consultations of 1477 asylum seekers and refugees
      have been documented during one month in 193 surgeries. The documented asylum
      seekers and refugees reflected the distribution of this population in
      Switzerland. Low consultation rates of asylum seekers and refugees in the
      majority of surgeries and high diversity of this population in respect to places
      of origin, education and proficiency in languages appear to be the major
      determinants of the difficulties in providing adequate health services to them.
      Readily available information on the past medical history and on the ethnic
      background of these patients and continuing education on specific topics
      concerning health care for asylum seekers and refugees were thought to be
      particularly useful. This needs to be considered in the planning of services for
      this group. General practitioners specialized in health care for asylum seekers
      and refugees is an option for providing improved specific services (interpreters,
      institutional links, culturally adapted medical care).

PMID- 9544468
TI  - [Asylum seekers and refugees in the medical polyclinic: a comparison between the
      Basel, Bern and Geneva polyclinics].
AB  - This cross-sectional study describes the state of health of asylum seekers and
      refugees and the health services provided to them by the medical outpatient
      departments of three major Swiss university hospitals, Basel, Berne and Geneva.
      The comparison of outpatient departments differing in organisational structure
      facilitated the identification of positive and negative determinants of health
      service provision. Questionnaires have been filled in by all physicians of the
      three medical outpatient departments (Basel: 10, Berne: 1, Geneva: 36). All
      consultations of asylum seekers and refugees have been recorded during the study
      period (Basel: 42, Berne: 93, Geneva: 187). Interviews have been done with the
      physicians who coordinated the study. During the study period the majority of the
      patients originated from former Yugoslavia, Turkey, Sri Lanka, Somalia, Angola
      and Zaire. One of the most prominent features of the population investigated has
      been its diversity in respect to countries of origin, languages, ability to
      communicate and education. Diversity and low consultation rates per physician
      could explain many of the problems which have been observed, e.g. the lack of
      experience in specific approaches to these patients or difficulties to provide
      interpreters. To improve the health care for this group of patients in medical
      outpatient departments small teams of physicians should be selected. By these
      means adequate levels of experience could be achieved and organizational problems
      could be dealt with more effectively. In addition, the relationship between
      specific problems of asylum seekers and refugees and more general issues of the
      interaction between physicians and patients are discussed in view of tasks in
      research and training.

PMID- 9544470
TI  - [Medical faculty of the Vienna University and national socialists--a perspective
      from a distance of 60 years].

PMID- 9544469
TI  - [Asylum seekers and refugees in the emergency department].
AB  - This cross-sectional study describes the health problems and the health care of
      asylum seekers and refugees from the point of view of accident & emergency (A &
      E) physicians at the major hospital in St. Gallen, Switzerland. The physicians
      filled in a detailed questionnaire and documented all consultations of asylum
      seekers/refugees and of a control group of patients during eleven weeks (2 x 98
      consultations). 76% of these asylum seekers/refugees originated from former
      Yugoslavia. The distribution of the main ICD-coded diagnoses did not differ
      between asylum seekers/refugees and the control group after correction for age.
      In comparison with the asylum seekers and refugees attending GPs, injuries were
      much more common in the A & E department attenders (37% vs. 8%). Asylum
      seekers/refugees and the patients in the control group did not differ in respect
      to being classified as an emergency case (58% vs. 65%). There were also no
      differences in hospitalisation rates (29% vs. 36%). Asylum seekers/refugees who
      were registered with a GP attended the A & E department more often during the
      night than during the day compared to patients who were not registered with a GP.
      Consultations which have been classified as emergencies occurred more frequently
      during the day than at night time. The time of residence in Switzerland was
      negatively associated with the registration with a GP and with being classified
      as an emergency case. A lack of experience in caring for asylum seekers and
      refugees and of specific training in this field has been the major complaint by
      the A & E physicians. Asylum seekers should be introduced to the tasks and
      functions of the various sectors of the national health care system as early as
      possible. Registration with a GP in the community should be promoted.

PMID- 9544471
TI  - [Racial eugenics in Vienna 1938].

PMID- 9544472
TI  - [Political misuse of science: biology in the Third Reich].

PMID- 9544473
TI  - [Previously unrecognized significance of national socialism for Vienna medicine].

PMID- 9544474
TI  - ["Guiding" instead of healing. On some discoveries from the Vienna Public Health
      Office 1938-1945].

PMID- 9544475
TI  - [Opportunists, sympathists and officials. Support of the national socialism
      system at the Vienna Academy of Sciences, exemplified by the efforts of Nadler,
      srbink and Meister].

PMID- 9544477
TI  - [Arthur Schuller, father of neuroradiology or: an Austrian scientist's fate].

PMID- 9544478
TI  - Edelweiss to kangaroo paw.

PMID- 9544476
TI  - Austrian medical refugees in Great Britain: from marginal aliens to established
      professionals.
AB  - About 360 Austrian physicians were refugees in the UK between 1938 and 1945. This
      paper traces their experiences. Apart from a scheme to admit only fifty
      physicians and forty dental surgeons, support ranged from domestic service
      permits to the backing from scientists keen to modernize British medicine. After
      the wave of internments in 1940, it was possible for physicians to be placed on
      the Temporary Register of Medical Practitioners. Three case studies of three
      types of Austrian contributions to child health are presented. The position
      improved after World War 2 when full registration of Austrian qualifications
      became possible, and the National Health Service provided career opportunities
      for clinical specialists. Only circa 10% of the medical refugees from Austria
      returned there eventually. Examples are given of successful careers in a wide
      range of medical specialties.

PMID- 9544479
TI  - From personae non gratae in Vienna 1938 to respected citizens of Edinburgh: a
      vignette of my parents Dr. Ernst Adler and Dr. Regina Kapeller-Adler.

PMID- 9544480
TI  - The silence of words--some thoughts on the Pernkopf Atlas.

PMID- 9544481
TI  - [The scientific development in dermatology in Germany in relation to the
      emigration of Jewish dermatologists during national socialism].
AB  - The anti-semitic laws let to the persecution of the Jews in Germany during the
      time of National Socialism. About 600 Jewish dermatologists had to suffer from
      the prohibition of their profession. 63% of them left Germany. The emigrants
      mainly preferred to move out to the U.S. The policy of coordination and
      elimination of the National Socialists led to the reappointment of dermatological
      chairs in universities. The National Socialists also forced the change in the
      boards of dermatological societies and the change of the editorial boards of
      dermatological journals. All papers of the three leading dermatological journals
      were analysed for the evaluation of the development of science. The assessment
      included the number of articles, the origin of the authors and the contents of
      articles (research, clinics, diagnostic, therapy). From 1933 to 1945 the number
      of papers per year decreased consequently, especially during the Second World
      War. During the whole time the number of German authors increased and the number
      of abroad living authors decreased. There was a very good and interesting
      international exchange of information in the journal "Archiv fur Dermatologie und
      Syphilis". The activity reduced clearly after the beginning of the Second World
      War in 1939. The analysis of contents resulted in a reduction of basis science
      research and an orientation to the clinical research. Papers about therapeutical
      possibilities were always published. The emigration of Jewish dermatologists led
      to a continuous reduction of scientific activities and to an extensive
      international isolation.

PMID- 9544482
TI  - [Ernst Klee: Auschwitz, national socialist medicine and its victims].

PMID- 9544483
TI  - Eduard Pernkopf's atlas of anatomy or: the fiction of "pure science".

PMID- 9544484
TI  - The Wiener klinische Wochenschrift from 1938 to 1945. On the 50th anniversary of
      its reappearance in 1946.

PMID- 9544486
TI  - [The intestine as the cause of infection and multiple organ failure].

PMID- 9544487
TI  - [Significance of small intestine mucosa as a metabolic organ].

PMID- 9544488
TI  - [Physiology and pathophysiology of intestinal flora].

PMID- 9544489
TI  - History of the Department of Pediatrics Yale University School of Medicine.
AB  - The history of pediatrics at the Yale University School of Medicine can be
      divided into eight historical eras. The "Paleohistorical Era" included colonial
      figures such as Governor John Winthrop and Hezekiah Beardsley who wrote about
      children's disease in colonial times. Eli Ives, Professor of the Diseases of
      Children at Yale Medical School gave the first systematic pediatric course in
      America in the first half of the nineteenth century. During the second era, from
      1830-1920, the New Haven Hospital was opened. An affiliation between Yale
      University and the New Haven Hospital led to the formal establishment of clinical
      departments including pediatrics in the early 20th century. Six eras coinciding
      with successive pediatric chairman have led the department to its present
      respected position in American pediatrics. The department's 75th anniversary in
      1996 is an occasion to recognize many of the department's accomplishments and
      leaders over the years. It is also a time to reaffirm the mission of the
      department: to the health needs of the children of Connecticut and beyond, to the
      advancement of scientific knowledge of infants and children and their diseases,
      and to the training and educational of the pediatric clinicians, educators and
      investigators of the future.

PMID- 9544490
TI  - Yale pediatrics: today and into the 21st century.

PMID- 9544491
TI  - Building bridges between academia and industry: forms; foundations; functions.

PMID- 9544492
TI  - Iron deficiency: lessons from anemic mice.
AB  - Iron is an essential nutrient, and disorders of iron metabolism are common.
      Nonetheless, intestinal iron absorption and cellular iron transport are poorly
      understood. Biochemical approaches to elucidating these processes have yielded
      little in the past decade. As an alternative approach, we have begun to study
      spontaneous mouse mutants, that have inherited defects in key steps in iron
      transport. We have undertaken positional cloning of the gene responsible for
      microcytic anemia (gene symbol mk). This report describes the important
      characteristics of these mice, and our progress in studying them.

PMID- 9544493
TI  - Preventing preterm birth: are we making any progress?
AB  - Most industrialized countries have reported recent decreases in the size of
      infants born at term but no reduction, or even a rise in the incidence of preterm
      birth. This paper reviews recent secular trends in preterm birth and the evidence
      about possible reasons for those trends. The hypothesized reasons include
      ignorance about the causal determinants of preterm birth, failure to reduce
      exposure to recognized determinants, increases in multiple births, the use of
      early ultrasound (rather than menstrual dates) to estimate gestational age, early
      induction or cesarean section for pregnancy complications, and registration of
      extremely immature births of borderline viability.

PMID- 9544495
TI  - [Use of metal stents in gastroenterology].
AB  - A variety of metal stents have been increasingly used for malignant esophageal,
      biliary and colorectal stenoses. Esophageal self-expandable stents significantly
      reduce the early morbidity after implantation compared to conventional plastic
      prostheses. However they offer no benefit in the long-term due to various late
      complications. Biliary stents offer a significantly longer patency than plastic
      devices. This advantage is however clinically relevant only for patients with a
      survival time of more than three months. Preliminary trials indicate promising
      results for palliation of colorectal stenoses with metal stents in selected
      cases. Due to a lack of comparative studies the different types of metal stents
      must be selected on basis of their physical characteristics and clinical
      experiences. Most of the prostheses are irremovable which is a limitation for use
      in benign stenoses of the gastrointestinal and biliary tract. In addition metal
      stents are extremely expensive so that carefully designed trials are warranted
      for evaluation of the cost-benefit ratio.

PMID- 9544494
TI  - [Guidelines of the German Society of Digestive and Metabolic Diseases. Guidelines
      for endoscopic colorectal polypectomy with the sling. German Society of Digestive
      and Metabolic Diseases].

PMID- 9544496
TI  - Evaluation of a cacao drink as a simple oral stimulus to assess gallbladder
      contraction.
AB  - Gallbladder contractility plays an important role in the pathogenesis of
      gallstones and in the course of cholelithiasis. Furthermore, a functioning
      gallbladder is an important condition for performing a successful disolution of
      gallstones by bile acids. Therefore, a reliable simple physiological test is
      desired to assess gallbladder contractility. In ten volunteers gallbladder
      contraction was stimulated by 50 g chocolate, 330 ml cacao drink or in comparison
      by intramuscular injection of 0.3 microgram/kg ceruletide. Gallbladder volume was
      measured sonographically and CCK in serum was determined by radioimmunoassay
      (RIA) after 0, 15, 30 and 45 min. Additionally gallbladder contraction was
      determined in 20 patients with symptomatic gallstones using cacao drink on
      ceruletide. In health volunteers remaining gallbladder volume after 30 min was
      28% +/- 5% using ceruletide and 37% +/- 7% using cacao. Stimulation by chocolate
      resulted in a remaining volume of 59% +/- 12% after 45 min only. Simultaneously
      to gallbladder contraction an increase of CCK in serum was registered. 30 min
      after cacao CCK had increased from 0.9 to 3.3 pmol/l. Using chocolate an increase
      of CCK amounted to 2.1 pmol/l after 45 min only. In patients with gallstones the
      positive predictive value of the cacao test for a functioning gallbladder was 91%
      and the negative predictive value was 78% in comparison to the unphysiologic
      stimulation by ceruletide injection. CONCLUSION: Cacao test but not chocolate is
      suitable and reliable to assess gallbladder contraction in patients with
      symptomatic gallstones.

PMID- 9544497
TI  - Evaluation of four methods for detection of Clostridium difficile or C. difficile
      toxin: cytotoxin assay, culture, latex agglutination, and a new rapid immunoassay
      (C. difficile toxin A test).
AB  - The performance of C. difficile toxin A test (Oxoid, Basingstoke, UK), an
      immunoassay for the detection of C. difficile toxin A in fecal samples, for the
      diagnosis of C. difficile-associated diarrhea was compared with those of
      cytotoxin assay, culture, and a latex agglutination assay (Culturette Brand CDT
      Rapid Clostridium difficile test; Becton Dickinson, Cockeysville, MD). A total of
      105 stool specimens from 71 patients were tested. Of the 105 specimens analyzed,
      6 (5.7%) samples were positive by all four methods, 66 samples (62.9%) were
      concordant negative. Two patients fulfilled all clinical criteria for C.
      difficile-associated diarrhea but had negative results in the cytotoxicity tests.
      The sensitivity and specificity, as determined against cytotoxin assay results,
      were, respectively 52.4% and 93.9% for latex agglutination, 68.2% and 84.3% for
      rapid immunoassay and 36.4% and 92.8% for culture. No single laboratory test
      yields a definitive diagnosis of C. difficile-associated diarrhea at present.
      Test results by any of these methods must be used in conjunction with patient
      history when making the diagnosis to avoid indiscriminate treatment of
      individuals without disease or the lack of treatment for individuals with a
      serious infection. We consider the rapid and easy-to-perform C. difficile toxin A
      test not to be an essential adjunct for the diagnosis of C. difficile-associated
      diarrhea.

PMID- 9544498
TI  - [Value of endosonography in diagnosis of diffusely growing stomach carcinomas].
AB  - The diagnosis of diffuse type gastric carcinoma is very difficult. The delay of
      diagnosis is often due to false-negative endoscopic and histologic evaluation.
      The architecture of the stomach can be clearly visualized by endosonography.
      Therefore, already minor destructions of the gastric layers can be found. The
      endosonographic picture includes the presence of the layers, which are larger and
      of irregular contour. In infiltrating gastric cancer typically the submucosal
      layer and the muscularis are concentrically enlarged and appear folded. Based on
      the endosonographic picture diffuse type gastric carcinoma has been diagnosed in
      32 patients. When compared to the histologic diagnosis after gastrectomy or
      autopsy the accuracy of the endosonographic diagnosis was 87.5%, (28 out of 32
      patients). From the remaining four patients diagnosed to have diffuse type
      gastric cancer by endosonography three patients turned out to have malignant
      infiltrating tumors of different histologies. Therefore, the positive predictive
      value of endosonography in detection of infiltrating malignant tumors was 96.8%
      in our group. In contrast the accuracy of preoperative histologic diagnosis by
      biopsies was only 58%. Suspicious results of gastroscopy, especially in
      combination with a negative biopsy, should lead to further evaluation by
      endosonography to detect diffuse type gastric cancer earlier.

PMID- 9544499
TI  - Transjugular intrahepatic portosystemic stent-shunt after orthotopic liver
      transplantation in a patient with early recurrence of portal hypertension of
      unknown origin.
AB  - A 65-year-old italian patient developed complicated portal hypertension
      immediately after orthtopic liver transplantation (OLT) necessitating shunt
      creation. One to five weeks after OLT, massive ascitic fluid losses of up to
      121/day developed. Vascular and major hepatic-parenchymal abnormalities were
      excluded by duplexsonography, angiography and initial histology, respectively. A
      peritoneovenous shunt (Denver-shunt) on day 31 after OLT reduced (by about 50%)
      but did not stop ascitic fluid losses. Furthermore, three variceal bleedings
      occurred after implantation of the Denver-shunt. Direct portography on day 45
      after OLT revealed portal hypertension (pressure gradient of 26 mmHg) requiring
      the implantation of a transjugular intrahepatic portosystemic stent-shunt (TIPS)
      leading to a reduction of the pressure gradient to 13 mmHg. Subsequently, ascites
      resolved within ten days and esophageal varices improved. Liver function
      parameters normalized inspite of recurrence of HCV infection with detection of
      HCV RNA in serum already in the fifth week after OLT. During follow-up,
      histological findings deteriorated from mild changes to extended fibrosis at day
      61 after OLT, which might have contributed to the maintenance of portal
      hypertension. The deterioration of liver histology was accompanied by an
      improvement/normalization of liver graft function. There was no evidence for
      additional viral liver infections, e.g. hepatitis B or cytomegalovirus infection.
      This case illustrates an etiologically unclear syndrome developing directly after
      OLT and reaffirms the effectiveness of TIPS in the treatment of complicated
      portal hypertension even after liver transplantation.

PMID- 9544500
TI  - [Protein-losing giant fold gastritis in childhood--a case report and
      differentiation from Menetrier disease of adulthood].
AB  - We report on a 2.5-year-old boy, who presented with vomiting since one week and
      periorbital and pitting edema. Laboratory studies revealed hypoproteinemia and
      hypoalbuminemia without signs of renal or liver disease. The cause of protein
      loss was giant fold gastritis disclosed by upper endoscopy. Biopsies revealed
      foveolar hyperplasia with cystic dilatation of the glands, identical to
      Menetrier's disease in adulthood. About 55 cases of hypertrophic gastropathy in
      children have been published. In contrast to the chronic course of Menetrier's
      disease in adults, the pediatric cases are generally benign, self-limited with
      complete resolution typically within a few weeks. While the etiology of
      Menetrier's disease is still unknown, the benign pediatric hypertrophic
      gastropathies have been associated with infections, primarily CMV and
      occasionally helicobacter pylori, herpes simplex and mycoplasma. Supportive
      treatment with a high-protein-diet and intravenous albumin transfusions is
      recommended. H2-receptor antagonists might improve symptoms.

PMID- 9544501
TI  - [A system of nonspecific defense in chronic inflammatory bowel diseases-
      pathophysiologic and therapeutic aspects].
AB  - Monocytes/macrophages are a prominent feature of the inflammatory infiltrate in
      inflammatory bowel disease (IBD). Progress in the development of monoclonal
      antibodies has provided a powerful means to identify and study various subsets of
      macrophages in the intestinal mucosa. In both Crohn's disease and ulcerative
      colitis distinct macrophage populations have been found being prominent in active
      disease, but absent from normal mucosa. Studies of our group show that the Ca(2+)
      binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10
      epitope) can be immunolocalized in the majority of granulocytes and macrophages
      in active but not inactive IBD. Serum MRP8/14 concentrations are significantly
      increased in patients with active IBD compared with patients suffering from
      inactive/mild disease. In vitro studies revealed that IL-13, IL-10 and IL-4
      strongly suppress secretion of monocytic proteins. Differential responses of
      monocytes and macrophages towards the inhibitory effects of TH2-cytokines can be
      observed in both patients with IBD and control groups. Combined treatment with
      TH2-cytokines may effectively suppress the response of activated
      monocytes/macrophages thus being of potential therapeutic benefit for patients
      with IBD.

PMID- 9544502
TI  - [Treatment of primary sclerosing cholangitis: drug, endoscopic, combined or no
      treatment at all?].

PMID- 9544503
TI  - [Stress proteins and molecular chaperones--protectors of intestinal epithelial
      damage?].

PMID- 9544504
TI  - [Does liver transplantation have the greatest chance of healing in cirrhosis with
      hepatocellular carcinoma?].

PMID- 9544505
TI  - The effect of serial dilution error on calibration inference in immunoassay.
AB  - A common practice in immunoassay is the use of sequential dilutions of an initial
      stock solution of the antigen of interest to obtain standard samples in a desired
      concentration range. Nonlinear, heteroscedastic regression models are a common
      framework for analysis, and the usual methods for fitting the model assume that
      measured responses on the standards are independent. However, the dilution
      procedure introduces a propagation of random measurement error that may
      invalidate this assumption. We demonstrate that failure to account for serial
      dilution error in calibration inference on unknown samples leads to serious
      inaccuracy of assessments of assay precision such as confidence intervals and
      precision profiles. Techniques for taking serial dilution error into account
      based on data from multiple assay runs are discussed and are shown to yield valid
      calibration inferences.

PMID- 9544508
TI  - Added risk and inverse estimation for count responses in reproductive aquatic
      toxicology studies.
AB  - One of the experimental designs used to evaluate the toxicity of certain
      chemicals in aquatic organisms focuses on reproductive output. Toxic effects are
      manifested through a reduced level of reproduction in exposed organisms.
      Historically, evaluating risks in this context has focused on changes in the mean
      reproduction in a population of organisms. In this paper, we focus on the toxic
      effects at the level of the individual organism. This new method for count
      responses involves added risk, the probability of the production of young being
      suppressed below certain specified levels in individuals exposed to a particular
      concentration level relative to the probability of that level of suppression in
      control organisms. This probability serves as the basis of the individual-based
      risk estimation procedures. In particular, inverse estimation of the
      concentration associated with a specified added risk and estimates of the added
      risk associated with a particular concentration are discussed in the context of a
      negative binomial regression model. Confidence intervals are constructed for both
      of these quantities using the delta method. These methods are illustrated with a
      study of an aquatic organism, Ceriodaphnia dubia, exposed to the herbicide
      nitrofen.

PMID- 9544509
TI  - A method for parametric estimation of the number and size distribution of cell
      clusters from observations in a section plane.
AB  - The problem of finding the number and size distribution of cell clusters that
      grow in an organ or tissue from observations of the number and sizes of
      transections of such cell clusters in a planar section is considered. This
      problem is closely related to the well-known corpuscle or Wicksell problem in
      stereology, which deals with transections of spherical objects. However, for most
      biological applications, it is unrealistic to assume that cell clusters have
      spherical shapes since they may grow in various ways. We therefore propose a
      method that allows for more general spatial configurations of the clusters. Under
      the assumption that a parametric growth model is available for the number and
      sizes of the cell clusters, expressions are obtained for the probability
      distributions of the number and sizes of transections of the clusters in a
      section plane for each point in time. These expressions contain coefficients that
      are independent of the parametric growth model and time but depend on which model
      is chosen for the configuration of the cell clusters in space. These results
      enable us to perform estimation of the parameters of the growth model by maximum
      likelihood directly on the data instead of having to deal with the inverse
      problem of estimation of three-dimensional quantities based on two-dimensional
      data. For realistic choices of the configuration model, it will not be possible
      to obtain the exact values of the coefficients, but they can easily be
      approximated by means of computer simulations of the spatial configuration. Monte
      Carlo simulations were performed to approximate the coefficients for two
      particular spatial configuration models. For these two configuration models, the
      proposed method is applied to data on preneoplastic minifoci in rat liver under
      the assumption of a two-event model of carcinogenesis as the parametric growth
      model.

PMID- 9544510
TI  - Change-point analysis of neuron spike train data.
AB  - In many medical experiments, data are collected across time, over a number of
      similar trials, or over a number of experimental units. As is the case of neuron
      spike train studies, these data may be in the form of counts of events per unit
      of time. These counts may be correlated within each trial. It is often of
      interest to know if the introduction of an intervention, such as the application
      of a stimulus, affects the distribution of the counts over the course of the
      experiment. In such investigations, each trial generates a sequence of data that
      may or may not contain a change in distribution at some point in time. Each
      sequence of integer counts can be viewed as arising from a Poisson process and
      are therefore independently distributed or as an integer-valued time series that
      allows for correlations between these counts. The main aim of this paper is to
      show how the ensemble of sample paths may be used to make inference about the
      distribution of the instantaneous times of change in a given population. This
      will be accomplished using a Bayesian hierarchical model for these change-points
      in time. A bonus of these models is they also allow for inference about the
      probability of a change in each unit and the magnitude of the effects, if any.
      The use of such change-point models on integer-valued time series is illustrated
      on neuron spike train data, although the methods can be applied to other
      situations where integer-valued processes arise.

PMID- 9544511
TI  - Three approaches to regression analysis of receiver operating characteristic
      curves for continuous test results.
AB  - The accuracy of a medical diagnostic test is typically summarized by the
      sensitivity and specificity when the test result is dichotomous. Receiver
      operating characteristic (ROC) curves are measures of test accuracy that are used
      when test results are continuous and are considered the analogs of sensitivity
      and specificity for continuous tests. ROC regression analysis allows one to
      evaluate effects of factors that may influence test accuracy. Such factors might
      include characteristics of study subjects or operating conditions for the test.
      Unfortunately, regression analysis methods for ROC curves are not well developed
      and methods that do exist have received little use to date. In this paper, we
      propose and compare three very different regression analysis methods. Two are
      modifications of methods previously proposed for radiology settings. The third is
      a special case of a general method recently proposed by us. The three approaches
      are compared with regard to settings in which they can be applied and
      distributional assumptions they require. In the setting where test results are
      normally distributed, we elucidate the correspondence between regression
      parameters in the different models. The methods are applied to simulated data and
      to data from a study of a new diagnostic test for hearing impairment. It is hoped
      that the presentation in this paper will both encourage the use of regression
      analysis for evaluating diagnostic tests and help guide the choice of the most
      appropriate regression analysis approach in applications.

PMID- 9544512
TI  - Inference for odds ratio regression models with sparse dependent data.
AB  - Suppose the number of 2 x 2 tables is large relative to the average table size,
      and the observations within a given table are dependent, as occurs in
      longitudinal or family-based case-control studies. We consider fitting regression
      models to the odds ratios using table-level covariates. The focus is on methods
      to obtain valid inferences for the regression parameters beta when the dependence
      structure is unknown. In this setting, Liang (1985, Biometrika 72, 678-682) has
      shown that inference based on the noncentral hypergeometric likelihood is
      sensitive to misspecification of the dependence structure. In contrast,
      estimating functions based on the Mantel-Haenszel method yield consistent
      estimators of beta. We show here that, under the estimating function approach,
      Wald's confidence interval for beta performs well in multiplicative regression
      models but unfortunately has poor coverage probabilities when an additive
      regression model is adopted. As an alternative to Wald inference, we present a
      Mantel-Haenszel quasi-likelihood function based on integrating the Mantel
      Haenszel estimating function. A simulation study demonstrates that, in medium
      sized samples, the Mantel-Haenszel quasi-likelihood approach yields better
      inferences than other methods under an additive regression model and inferences
      comparable to Wald's method under a multiplicative model. We illustrate the use
      of this quasi-likelihood method in a study of the familial risk of schizophrenia.

PMID- 9544513
TI  - Tests for homogeneity of the risk difference when data are sparse.
AB  - Test statistics for the homogeneity of the risk difference for a series of 2 x 2
      tables when the data are sparse is proposed. A weighted least squares statistic
      is commonly used to test for equality of the risk difference over the tables;
      however, when the data are sparse, this statistic can have anticonservative Type
      I error rates. Simulation is used to compare the proposed test statistics to the
      weighted least squares statistic. The weighted least squares statistic has the
      most anticonservative Type I error rates of all the statistics compared. We
      suggest the use of one of our proposed test statistics instead of the weighted
      least squares statistic.

PMID- 9544514
TI  - Interpreting the beta geometric in comparative fecundability studies.
AB  - The beta distribution has often been used to describe variation in fecundability
      between couples when modelling the number of menstrual cycles required for a
      couple to achieve pregnancy. Groups are often compared for a condition or factor
      that could affect conception rates. However, when heterogeneity is present in
      each group, comparing group-specific parameters is not very informative on what
      any differences might imply for the individual couples. We present a quantile
      ratio that provides an individual level interpretation of any between-group
      differences in the beta distribution. Our results are illustrated on the two
      examples of Ridout and Morgan (1991, Biometrics 47, 1423-1433). The quantile
      ratio suggests a simplification in one of the examples.

PMID- 9544515
TI  - Permutational distribution of the log-rank statistic under random censorship with
      applications to carcinogenicity assays.
AB  - In the random censorship model, the log-rank test is often used for comparing a
      control group with different dose groups. If the number of tumors is small, so
      called exact methods are often applied for computing critical values from a
      permutational distribution. Two of these exact methods are discussed and shown to
      be incorrect. The correct permutational distribution is derived and studied with
      respect to its behavior under unequal censoring in the light of recent results
      proving that the permutational version and the unconditional version of the log
      rank test are asymptotically equivalent even under unequal censoring. The log
      rank test is studied by simulations of a realistic scenario from a bioassay with
      small numbers of tumors.

PMID- 9544516
TI  - Conditional logistic regression with sandwich estimators: application to a meta
      analysis.
AB  - Motivated by a meta-analysis of animal experiments on the effect of dietary fat
      and total caloric intake on mammary tumorigenesis, we explore the use of sandwich
      estimators of variance with conditional logistic regression. Classical
      conditional logistic regression assumes that the parameters are fixed effects
      across all clusters, while the sandwich estimator gives appropriate inferences
      for either fixed effects or random effects. However, inference using the standard
      Wald test with the sandwich estimator requires that each parameter is estimated
      using information from a large number of clusters. Since our example violates
      this condition, we introduce two modifications to the standard Wald test. First,
      we reduce the bias of the empirical variance estimator (the middle of the
      sandwich) by using standardized residuals. Second, we approximately account for
      the variance of these estimators by using the t-distribution instead of the
      normal distribution, where the degrees of freedom are estimated using
      Satterthwaite's approximation. Through simulations, we show that these sandwich
      estimators perform almost as well as classical estimators when the true effects
      are fixed and much better than the classical estimators when the true effects are
      random. We achieve simulated nominal coverage for these sandwich estimators even
      when some parameters are estimated from a small number of clusters.

PMID- 9544517
TI  - Prediction of cumulative incidence function under the proportional hazards model.
AB  - In the presence of dependent competing risks in survival analysis, the Cox model
      can be utilized to examine the covariate effects on the cause-specific hazard
      function for the failure type of interest. For this situation, the cumulative
      incidence function provides an intuitively appealing summary curve for marginal
      probabilities of this particular event. In this paper, we show how to construct
      confidence intervals and bands for such a function under the Cox model for future
      patients with certain covariates. Our proposals are illustrated with data from a
      prostate cancer trial.

PMID- 9544518
TI  - Multiple imputation for early stopping of a complex clinical trial.
AB  - It is desirable to have procedures available for stopping a clinical trial early
      if there appears to be no treatment effect. Conditional power procedures allow
      for early stopping in favor of the null hypothesis if the probability of
      rejecting H0 at the planned end of the trial given the current data and a value
      of the parameter of interest is below some threshold level. Lan, Simon, and
      Halperin (1982, Communications in Statistics C1, 207-219) proposed a stochastic
      curtailment procedure that calculates the conditional power under the alternative
      hypothesis. Alternatively, predictive power procedures incorporate information
      from the observed data by averaging the conditional power over the posterior
      distribution of the parameter. For complex problems in which explicit evaluation
      of conditional power is not possible, we propose treating the problem of
      projecting the outcome of a trial given the current data as a missing data
      problem. We then complete the data using multiple imputation and thus eliminate
      the need for explicit calculation of conditional power. We apply this method to
      AIDS Clinical Trials Group (ACTG) protocol 118 and to several simulated clinical
      trials.

PMID- 9544519
TI  - An optimal design for screening trials.
AB  - Yao, Begg, and Livingston (1996, Biometrics 52, 992-1001) considered the optimal
      group size for testing a series of potentially therapeutic agents to identify a
      promising one as soon as possible for given error rates. The number of patients
      to be tested with each agent was fixed as the group size. We consider a
      sequential design that allows early acceptance and rejection, and we provide an
      optimal strategy to minimize the sample sizes (patients) required using Markov
      decision processes. The minimization is under the constraints of the two types
      (false positive and false negative) of error probabilities, with the Lagrangian
      multipliers corresponding to the cost parameters for the two types of errors.
      Numerical studies indicate that there can be a substantial reduction in the
      number of patients required.

PMID- 9544520
TI  - A strategy for dose-finding and safety monitoring based on efficacy and adverse
      outcomes in phase I/II clinical trials.
AB  - We propose a design strategy for single-arm clinical trials in which the goals
      are to find a dose of an experimental treatment satisfying both safety and
      efficacy requirements, treat a sufficiently large number of patients to estimate
      the rates of these events at the selected dose with a given reliability, and stop
      the trial early if it is likely that no dose is both safe and efficacious.
      Patient outcome is characterized by a trinary ordinal variable accounting for
      both efficacy and toxicity. Like Thall, Simon, and Estey (1995, Statistics in
      Medicine 14, 357-379), we use Bayesian criteria to generate decision rules while
      relying on frequentist criteria obtained via simulation to determine a design
      parameterization with good operating characteristics. The strategy is illustrated
      by application to a bone marrow transplantation trial for hematologic
      malignancies and a trial of a biologic agent for malignant melanoma.

PMID- 9544521
TI  - A Bayesian framework for intent-to-treat analysis with missing data.
AB  - In longitudinal clinical trials, one analysis of interest is an intention-to
      treat analysis, which groups subjects according to the randomized treatment
      regardless of whether they stayed on that treatment or not. When in addition to
      going off the randomized treatment subjects may also drop out of the study and be
      lost to follow-up, it is unclear what an intention-to-treat analysis should be.
      If measurements are made after treatment drop-out on a random sample of subjects
      who drop the treatment, then Hogan and Laird (1996, Biometrics 52, 1002-1017)
      present a random effects model, well suited to this type of analysis, which fits
      a two-piece linear spline to the data with the knot at the time the assigned
      treatment is dropped. This article presents a Bayesian approach to fitting a
      similar two-piece linear spline model and shows how the model can be applied to
      data that have no off-treatment observations.

PMID- 9544522
TI  - Sample size determination for phase II clinical trials based on Bayesian decision
      theory.
AB  - This paper describes an application of Bayesian decision theory to the
      determination of sample size for phase II clinical studies. The approach uses the
      method of backward induction to obtain group sequential designs that are optimal
      with respect to some specified gain function. A gain function is proposed
      focussing on the financial costs of, and potential profits from, the drug
      development programme. On the basis of this gain function, the optimal procedure
      is also compared with an alternative Bayesian procedure proposed by Thall and
      Simon. The latter method, which tightly controls type I error rate, is shown to
      lead to an expected gain considerably smaller than that from the optimal test.
      Gain functions with respect to which Thall and Simon's boundary is optimal are
      sought and it is shown that these can only be of the form considered, that is,
      with constant cost for phase III study and cost of the phase II study
      proportional to the sample size, if potential profit increases over time.

PMID- 9544523
TI  - Inference using conditional logistic regression with missing covariates.
AB  - When there are many nuisance parameters in a logistic regression model, a popular
      method for eliminating these nuisance parameters is conditional logistic
      regression. Unfortunately, another common problem in a logistic regression
      analysis is missing covariate data. With many nuisance parameters to eliminate
      and missing covariates, many investigators exclude any subject with missing
      covariates and then use conditional logistic regression, often called a complete
      case analysis. In this article, we derive a modified conditional logistic
      regression that is appropriate with covariates that are missing at random.
      Performing a conditional logistic regression with only the complete cases is
      convenient with existing statistical packages, but it may give bias if
      missingness is not completely at random.

PMID- 9544524
TI  - Comparison of meta-analysis versus analysis of variance of individual patient
      data.
AB  - Meta-analysis is a method of synthesizing the results of independent studies. We
      consider the case in which there are multiple treatments and a control, with the
      goal of estimating the relative effect of each treatment based on continuous
      outcomes. Even when all data are available, rather than only summary data, it has
      become common to use meta-analytic estimators of treatment contrasts.
      Alternatively, we could use a two-way analysis of variance model with no
      interaction in which one factor is study and one factor is treatment. For the
      unbalanced case, we obtain the surprising result that the standard meta-analysis
      estimates of treatment contrasts are identical to the least squares estimators of
      treatment contrasts in the linear model. Because a meta-analysis of individual
      patient data can be considerably more costly in terms of data retrieval than a
      meta-analysis of summary data, this equivalence provides for cost-efficient
      analysis.

PMID- 9544525
TI  - Sample size calculations based on slopes and other summary statistics.
AB  - Sample size calculations based on two-sample comparisons of slopes have been
      reported by many. This paper extends such discussions to include summary
      statistics other than slopes, such as post-baseline means, change scores, and
      final observations. Specifically, sample size formulas for analyses based on a
      broad class of summary statistics are presented, with modifications proposed to
      allow for missing data caused by staggered entry and random dropouts. The
      formulas developed are used to illustrate how required sample size is affected by
      summary statistic choice, variance parameters, the type of treatment difference
      of interest, and the manner in which incomplete observations are used in the
      analysis. An example based on longitudinal data from the Muscatine Study is
      presented.

PMID- 9544526
TI  - Power and sample size for stratified prospective studies using the score method
      for testing relative risk.
AB  - We derive the asymptotic power function of the score test for detecting a common
      relative risk greater than unity from multiple 2 x 2 tables and formulate methods
      of sample size determination for use when designing stratified prospective
      studies. The stratified score test is more efficient than the unstratified test
      when the latter is unbiased.

PMID- 9544527
TI  - Analysis of compositional bone density data using log ratio transformations.
AB  - In skeletal research, one of the techniques available to measure bone
      mineralization produces compositional data, which consist of vectors of ordered
      proportions of bone sample in prespecified density intervals. We investigated the
      value of two multivariate data transformations, the cumulative log ratio and the
      continuation log ratio, in the analysis of an experimental study of the dose
      response effect of a drug treatment on bone mineralization. Based on a comparison
      of alternative approaches to the analysis of compositional bone mineralization
      data in the application and in a simulation study, we recommend the use of the
      average of the cumulative log ratios over all the density intervals to detect
      change in the density distribution. We also recommend the use of one of the
      continuation log ratios when a specific density interval of interest can be
      specified a priori.

PMID- 9544528
TI  - Gibbs sampling for long-term survival data with competing risks.
AB  - Many researchers use the 5-year survival probability as a measurement of cure for
      long-term survival data. In addition to this probability, a mixture model with
      possibility of cure provides a predictive probability of cure given that a
      patient has survival to a period of time. Such probabilities are more realistic
      in measuring the effectiveness of the treatment and predicting the long-term
      survival of the patient than the 5-year survival rate. An extension of the cure
      model to the competing risks data is developed. The extended model is a finite
      mixtures model, where the independence of cause-specific failure times is not
      assumed. A data set consisting of leukemia with bone marrow transplant is used
      for illustration. Patients have three possible statuses after transplant: cured
      by the treatment, relapse of leukemia, or non-relapse-related death. Only the
      last two events are observable. Patients observed with these endpoints are
      uncensored cases and the transplant is not successful for them. A case is
      censored if the case is relapse-free and still alive at the end of its follow-up.
      Only censored cases have the possibility of being cured, but cure is not assumed
      to be observable. The status of cure is imputed by the posterior predictive
      probability of cure given the lifetime and is implemented in the Gibbs sampling.
      Cure is defined by assuming the risk for failure of a cured patient to be
      approximately zero. The probability of cure for the leukemia patients after the
      bone marrow transplant is about 27% for patients with the acute graft-versus-host
      disease (GVHD) and 46% for the non-GVHD group. The probability of relapse, given
      that one is not cured, is 0.50 for the non-GVHD group and 0.34 for the GVHD
      group. The non-GVHD group has a better chance of survival, while the GVHD group
      has a lower chance for relapse. This is known as the GVHD-versus-leukemia effect.

PMID- 9544529
TI  - Mixed effects logistic regression models for longitudinal binary response data
      with informative drop-out.
AB  - A shared parameter model with logistic link is presented for longitudinal binary
      response data to accommodate informative drop-out. The model consists of observed
      longitudinal and missing response components that share random effects
      parameters. To our knowledge, this is the first presentation of such a model for
      longitudinal binary response data. Comparisons are made to an approximate
      conditional logit model in terms of a clinical trial dataset and simulations. The
      naive mixed effects logit model that does not account for informative drop-out is
      also compared. The simulation-based differences among the models with respect to
      coverage of confidence intervals, bias, and mean squared error (MSE) depend on at
      least two factors: whether an effect is a between- or within-subject effect and
      the amount of between-subject variation as exhibited by variance components of
      the random effects distributions. When the shared parameter model holds, the
      approximate conditional model provides confidence intervals with good coverage
      for within-cluster factors but not for between-cluster factors. The converse is
      true for the naive model. Under a different drop-out mechanism, when the
      probability of drop-out is dependent only on the current unobserved observation,
      all three models behave similarly by providing between-subject confidence
      intervals with good coverage and comparable MSE and bias but poor within-subject
      confidence intervals, MSE, and bias. The naive model does more poorly with
      respect to the within-subject effects than do the shared parameter and
      approximate conditional models. The data analysis, which entails a comparison of
      two pain relievers and a placebo with respect to pain relief, conforms to the
      simulation results based on the shared parameter model but not on the simulation
      based on the outcome-driven drop-out process. This comparison between the data
      analysis and simulation results may provide evidence that the shared parameter
      model holds for the pain data.

PMID- 9544530
TI  - To use or not to use? Backward equations in stochastic carcinogenesis models.
AB  - The method based on the Kolmogorov backward equations of Little (1995, Biometrics
      51, 1278-1291) for computing hazard functions for the multistage carcinogenesis
      models fails when model parameters are time-dependent. In addition to suggesting
      an alternative method based on the Kolmogorov forward equation, this note
      highlights the interplay of the forward equation, the backward equation, and the
      characteristic method. Advantages and disadvantages of the forward and backward
      equations are discussed.

PMID- 9544531
TI  - The phosphatase system in Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae has at least six species of acid and alkaline
      phosphatases with different cellular localizations, as well as inorganic
      phosphate (Pi) transporters. Most of the genes encoding these enzymes are
      coordinately repressed and derepressed depending on the Pi concentration in the
      growth medium. The Pi signals are conveyed to these genes through a regulatory
      circuit consisting of a set of positive and negative regulatory proteins. This
      phosphatase system is interested as one of the best systems for studying gene
      regulation in S. cerevisiae due to the simplicity of phenotype determination in
      genetic analysis. With this methodological advantage, considerable amounts of
      genetic and molecular evidence in phosphatase regulation have been accumulated in
      the past twenty-five years. This article summarizes the current progress of
      research into this subject.

PMID- 9544532
TI  - Presence of wheat retrotransposons in Gramineae species and the origin of wheat
      retrotransposon families.
AB  - Distribution of wheat retrotransposon families (families 1 to 7) was examined in
      11 Gramineae species by the use of representative reverse transcriptase domain
      clones selected from six of the seven wheat retrotransposon families previously
      identified as probes. The homologues of families 3, 4, 5, and 7 retrotransposons
      were detectable only in the Pooideae species, suggesting that the distribution of
      the retrotransposons related to these families is restricted to the Pooideae
      subfamily. The representatives of families 1 and 2, distantly related to families
      3 to 7, revealed homologues additionally in the species outside the Pooideae
      subfamily including rice. These results suggest that the retrotransposons related
      to the former families have wider distribution than those related to families 3,
      4, 5, and 7. Analysis of a wheat genomic clone confirmed that the family 1
      representative reverse transcriptase domain clone is a Ty1-copia group
      retrotransposon derivative, which we have named Tar1. On the basis of these
      results, the origin of wheat retrotransposon families is discussed.

PMID- 9544534
TI  - Cranial thickness in American females and males.
AB  - To date, numerous studies have examined the range of cranial thickness variation
      in modern humans. The purpose of this investigation is to present a new method
      that would be easier to replicate, and to examine sex and age variation in
      cranial thickness in a white sample. The method consists of excising four cranial
      segments from the frontal and parietal regions. The sample consists of 165
      specimens collected at autopsy and 15 calvarial specimens. An increase in cranial
      thickness with age was observed. The results suggest that cranial thickness is
      not sexually dimorphic outside the onset of hyperostosis frontalis interna (HFI).

PMID- 9544535
TI  - Sex determination from the ribs of contemporary Turks.
AB  - There have been several in-depth studies showing that the sternal extremity of
      the fourth rib can be used in estimating age as well as in determining sex, as
      illustrated in North American whites and blacks. Yet biological differences
      between populations may preclude the cross-application of standards. To test this
      hypothesis and develop a sex determination standard for the Turkish population, a
      sample of the sternal ends of the fourth rib was collected from 294 individuals
      autopsied in Istanbul, Turkey. Dimensions from the superior edge to the inferior
      one (SI) and the anterior edge to its posterior edge (AP) were measured with a
      caliper. The sample was divided into three age groups, "young," "old," and
      "total." Using discriminant function analysis, three formulae were developed, one
      for each group. The results indicated that SI height is the most dimorphic
      dimension and that both dimensions together can given an accuracy of 86% to 90%.
      To reach such an accuracy, the age of the unknown should be estimated, at least
      whether it is phase 4 or above or below, using the age standards for ribs
      developed by Iscan and associates. When cross-validation tests are carried out,
      incorrect formulae reduce accuracy by as much as 20%. Furthermore, it was
      observed that North American based white sex determination formulae assign many
      Turkish males into a female category. In conclusion, it is important to note that
      population and age specificity are essential in determining sex from the rib. Yet
      its accuracy is as good as, if not better than, many bones of the postcranial
      skeleton.

PMID- 9544536
TI  - Excavation of a Vietnam-era aircraft crash site: use of cross-cultural
      understanding and dual forensic recovery methods.
AB  - The excavation of a 23 year-old aircraft crash site in the Socialist Republic of
      Vietnam and the transformational processes preceding its excavation in 1995-1996
      are detailed. The history of the site involved an initial catastrophic event,
      with subsequent reclamation and disturbances. Ultimately, a recovery effort by a
      joint U.S. team from the Central Identification Laboratory, Hawaii (CILHI). Joint
      Task Force-Full Accounting (JTF-FA) and a Socialist Republic of Vietnam
      contingent yielded numerous human remains, personal effects, and life-support
      items from the crash site. This case study should be of interest to the
      increasing number of forensic anthropologists who carry out work in international
      contexts. The application of forensic anthropology in human rights abuse cases,
      for example in Rwanda, Argentina, and Bosnia, provide examples of such cross
      cultural endeavors. Cultural factors act in the development of a site and should
      not be overlooked as significant taphonomic agents. The approach that an
      indigenous person takes to a crash site or mass grave may be quite different from
      our own approach, involving Western science. Holland, Anderson, and Mann (I)
      describe the postmortem alternation of exhumed and/or curated bone caused by
      indigenous South-east Asian peoples; the examples provided by these authors
      demonstrate how culture affects the treatment of what we would call "evidence."
      The international nature of an incident can add complicating "filters" to the
      reconstruction of events, since reclamation responses by indigenous people vary
      according to their interpretations of the scene. An investigating forensic
      anthropologist needs to understand the emic viewpoint (the insider's view), as
      cultural anthropologists do, when attempting to recover and reconstruct such an
      incident. In response to the cultural (and natural) taphonomic agents at work on
      such a site, the use of dual forensic recovery methods--simultaneously treating
      the investigation scene like an aircraft crash and a clandestine burial site--is
      advised. Employing a flexible set of methods will allow for maximal recovery of
      evidence.

PMID- 9544537
TI  - Short UV luminescence for forensic applications: design of a real-time
      observation system for detection of latent fingerprints and body fluids.
AB  - An assembly that allows a pseudo real-time (one second delay) observation of
      latent fingerprints by their short ultraviolet luminescence was designed. It is
      composed of a mercury-xenon lamp and a CCD camera, both water-cooled and computer
      controlled. The system is used to study the behaviour of latent fingerprints and
      stains of body fluids such as blood, semen and saliva under short-UV
      illumination.

PMID- 9544538
TI  - Evaluation of the human hair root for DNA typing subsequent to microscopic
      comparison.
AB  - Telogen human hairs are one of the most common useful evidence findings at crime
      scenes and/or on homicide victims. Occasionally, the microscopic characterization
      of the found telogen hair is the only physical evidence association to a victim
      or suspect. Recently efforts to characterize these hairs by mitochondrial DNA
      (mtDNA) methods have progressed. The nature of the telogen hair root morphology
      and ultrastructure has, however, been largely ignored. Examiners have recognized
      these hairs are unlikely to be typable by nuclear DNA (nuDNA) methods. Most
      forensic biologists have little knowledge of the complex cellular composition of
      anagen, catagen, and telogen hair roots or their morphogenesis. This paper
      reviews ex situ human hair root morphology as it relates to the likelihood of
      successful nuclear DNA typing. Dermatology texts of hair root morphology always
      demonstrate their microscopic appearance in the skin. This study investigates the
      use of fluorescence in situ hybridization (FISH) methods to sex type telogen head
      hairs, and it further investigates hair root morphology as it relates to the
      potential nuclear DNA content of evidence hairs. There is a need for the use of
      appropriate, consensus terminology for describing hair root morphology. There is
      also a need for standardized laboratory light microscopic methods in evaluating a
      hair root for DNA typing. FISH was found to be an unsuitable technique for sex
      determination of telogen hair clubs. It was determined that anagen/catagen hair
      roots without translucent sheath material are excellent candidates for nuDNA PCR
      based typing and that hairs with telogen club root material only should not be
      submitted for nuDNA typing attempts.

PMID- 9544539
TI  - Rapid PCR for identity testing using a battery-powered miniature thermal cycler.
AB  - A microfabricated, battery-powered thermal cycler was implemented in PCR-based
      DNA typing for human identification. HLA DQ alpha and an STR triplex were PCR
      amplified using a device known as the Miniature Analytical Thermal Cycling
      Instrument (MATCI). The extremely efficient heating properties of the MATCI
      enabled thermal cycling to be completed in as little as 21 min. In addition, the
      feasibility of using the real-time fluorescent detection system of the MATCI was
      demonstrated. The successful application of this portable, prototype device to
      forensic identity testing is a significant milestone towards the eventual
      development of a completely integrated DNA testing instrument that would also
      incorporate sample preparation and allele detection.

PMID- 9544540
TI  - Post-traumatic movement disorders: effect of the legal system on outcome.
AB  - Since patients with post-traumatic, neurologic, movement disorders often seek
      legal counsel and become involved in litigation, we used this group of disorders
      as a model for testing the hypothesis that an interaction with the legal system
      may influence its outcome. We reviewed 100 consecutive medical records of
      patients with post-traumatic movement disorders from the Movement Disorders
      Clinic at the Baylor College of Medicine. Additionally, 40 patients completed a
      detailed questionnaire and a health survey. Nineteen of the 40 respondents had
      obtained legal representation in regards to compensation for their medical
      problems. The group of patients with attorneys differed from those without legal
      representation in that they were significantly younger and a significantly higher
      percentage of these patients were disabled as compared to the group without
      attorneys. While most were dissatisfied with the legal system, 68% were satisfied
      with services provided by their attorneys. Although the patients with legal
      aspects of their movement disorders seemed to have more severe and persistent
      disability, we could not definitely conclude that the legal system had adversely
      affected the outcome of the post-traumatic movement disorders.

PMID- 9544541
TI  - Criminal and behavioral aspects of juvenile sexual homicide.
AB  - This preliminary research provides a descriptive, systematic study of juvenile
      sexual homicide. Fourteen incarcerated juveniles, identified through a department
      of corrections computer search, were assessed using a structured diagnostic
      interview, an author-designed clinical interview, and a review of correctional
      files and other available records. Five of the offenders' victims survived the
      homicidal attack, but their cases were nevertheless included in this study as the
      offenders' intent was clearly to kill their victim, and the victim's survival was
      merely by chance. All victims were female and all offenders were male. Their
      crimes typically occurred in the afternoon, and involved a low-risk victim of the
      same race who lived in the offender's neighborhood. The sexual component of the
      crime consisted of vaginal rape in over one-half of the cases. Weapons, typically
      a knife or bludgeon, were used in all but one case. Thirteen of these youths had
      a prior history of violence, and twelve had previous arrests. Chaotic, abusive
      backgrounds and poor adjustment in school were typical for these boys. A conduct
      disorder diagnosis was present in twelve of the youths, and violent sexual
      fantasies were experienced by one-half of the sample. The findings in this study
      suggest that juvenile sexual murderers comprise less than 1% of juvenile
      murderers, and are likely to be an emotionally and behaviorally disturbed
      population with serious familial, academic, and environmental vulnerabilities.

PMID- 9544542
TI  - Accuracy of bite mark overlays: a comparison of five common methods to produce
      exemplars from a suspect's dentition.
AB  - Physical comparison of a suspect's teeth to a bite mark injury using hollow
      volume comparison overlays is a common forensic odontology technique. Several
      methods are used to record characteristics of the size, shape and position of the
      teeth and to generate overlays. These include computer-based, radiographic,
      xerographic and hand-traced methods. Five common overlay production methods were
      compared using digital images of dental study casts as a reference standard. Area
      of the biting edges of the anterior teeth and relative rotation of each anterior
      tooth were measured and compared. The computer-based production method was
      determined to be the most accurate of those studied. It produced accurate
      representations of the biting edges of the teeth in an objective manner. The
      radiographic method was determined to be more accurate than the xerographic
      method with respect to tooth area measurement. The opposite is true with respect
      to tooth rotation. Hand-traced methods, from either wax impressions of teeth or
      directly from study casts, were determined to be inaccurate and subjective. It is
      recommended that forensic odontologists discontinue the use of hand-traced
      overlays in bite mark comparison cases.

PMID- 9544543
TI  - The natural decomposition of adipocere.
AB  - Adipocere is a waxy substance which sometimes forms from the adipose tissue of
      dead bodies, especially when they are under water. A disinterment in southern
      Ontario lead to the recovery of extensive adipocere from an interment which
      occurred in AD 1869. Subsequent laboratory research was designed to explore the
      conditions under which adipocere will disappear, the goal being to identify
      strategies for estimating a range of time since death in cases where adipocere is
      present. Varieties of aerobic or facultatively anaerobic microorganisms from the
      surface of the adipocere were separated and identified. In culture, the gram
      positive bacteria were able to degrade the adipocere. We propose that the
      persistence of adipocere is related to the exclusion of gram positive bacteria
      from the burial environment. The role of bacteria in adipocere formation and
      degradation must be understood before we can use the presence of adipocere to
      extrapolate information about the post-death interval.

PMID- 9544544
TI  - A 15 year retrospective review of homicide in the elderly.
AB  - With constant improvements in socioeconomic conditions, the people of most
      industrialized nations are living longer. Most elderly individuals lead
      productive lives within the community. Unfortunately, when elderly individuals
      suffer from a debilitating disease or injury, society seems ill-equipped to care
      for them. The frailty and social isolation that comes with illness or advanced
      age renders the elderly more vulnerable to crime. This study examines the
      circumstances that surround homicides of those 65 years of age or older which
      occurred in Jefferson County, Alabama over a 15 year span. We conducted a
      retrospective study of all decedents brought to the Jefferson County
      Coroner/Medical Examiner Office during the 15 years from 1981-1995. A computer
      search identified 150 homicide victims who were 65 years or older. In these 150
      cases the causes of death were as follows: gunshot wound 50%, blunt force
      injuries 19%, knife wounds 14%, and asphyxiation 10%. Younger homicide victims
      were much less likely to be killed as the result of a direct physical assault;
      blunt force injuries and asphyxiation combined caused death in only 7% of the
      younger population. Robbery was the most common motive for death in the elderly
      population, which accounted for 37% of cases. The most common location for
      homicides in the elderly population was in their own residence, which accounted
      for 71% of cases. Four elderly homicide victims were shot by the police. Three
      elderly decedents died as a result of abuse.

PMID- 9544545
TI  - Subdural neomembranes and sudden infant death syndrome.
AB  - Cranial dura maters of 36 consecutive infants with sudden infant death syndrome
      (SIDS) and 16 control infants coming to the Department of Coroner were examined
      microscopically to determine if subdural neomembranes are associated with cases
      submitted as SIDS. Thirty-one percent (31%) of the infants with SIDS and 13% of
      control infants had organizing subdural neomembranes (p > 0.05). Overall
      prevalence of organizing subdural neomembranes was 25% in the group examined. In
      all but two cases, birth trauma could be excluded as a cause of head trauma by
      aging neomembranes histologically. No association was found between type of
      delivery (vaginal or Cesarean) and presence of a subdural neomembrane. Subdural
      neomembranes are common in infants autopsied in a forensic setting, but they may
      be missed without a microscopic examination. Subdural neomembranes have no
      demonstrated association with SIDS.

PMID- 9544546
TI  - Death investigation in Canada.
AB  - A survey of death investigation systems in Canada was conducted by questionnaire
      and included questions on the type of system used (coroner or medical examiner),
      budget, method of appointment and qualifications of coroners and medical
      examiners, responsible department of government, training requirements,
      laboratory facilities, and the utilization of investigators and pathologists by
      each jurisdiction. Of the population of Canada 81.5% reside in coroner
      jurisdictions, the primary death investigator in 81% of the population is a
      licensed physician. The majority of jurisdictions either require or provide
      training in death investigation. All death investigation systems are under the
      respective provincial or territorial department of Justice or Attorney General
      with the chief coroner or chief medical examiner appointed by their respective
      provincial cabinet. The qualifications of the chief coroner vary with
      jurisdiction, while in 75% of medical examiner jurisdictions the chief medical
      examiner must be a pathologist. On a per capita basis medical examiner systems
      are less expensive to operate than coroner systems.

PMID- 9544547
TI  - Postmortem amitriptyline pharmacokinetics in pigs after oral and intravenous
      routes of administration.
AB  - In this study we have evaluated the postmortem pharmacokinetics of amitriptyline
      (Ami) and metabolites in pigs after oral and intravenous administration, and the
      results are compared with previous studies in rats and humans. In addition a
      meticulous investigation of blood and tissue concentrations after postmortem
      intravenous infusion of Ami was undertaken. Of a total of 9 over-night fasted
      pigs, 3 were given 25 mg/Kg Ami orally, and another 3 pigs received an
      intravenous infusion lasting 1 h of 3.3 mg/Kg Ami prior to death. The final 3
      pigs were sacrificed and then given the intravenous infusion after death. After
      approximately 5 h at room temperature, all carcasses were subsequently stored at
      4-5 degrees C. Postmortem blood samples were collected at 0.25, 1, 2, 4, 8, 24,
      48, and 96 h through an indwelling intracardial needle. Postmortem examination
      with blood and tissue sampling was performed 96 h after death. Analysis was
      carried out by high performance liquid chromatography with ultraviolet detection.
      Postmortem blood samples from the heart of the orally dosed animals revealed
      large and variable concentration increases of 99(30-243)% for Ami and 96(52-429)%
      for the main metabolite 10-OH-Ami at 96 h. In the intravenously infused live pigs
      heart blood Ami increased by 55(33-69)% and 10-OH-Ami increased by 232(76-240)%.
      Blood from the atria had significantly higher Ami concentrations than blood from
      both ventricles in the animals dosed while alive, and the drug concentration in
      femoral blood was higher than in heart blood (p < 0.01). In the orally dosed pigs
      the left lobe of the liver had significantly higher Ami levels than the right
      lobe. Tissue/blood Ami concentration ratios were generally lower than previously
      reported in rats and approximating the levels reported in humans. The animals
      infused intravenously after death demonstrated high drug levels in blood samples
      from central vessels, heart, lungs as well as cerebrospinal fluid and vitreous
      humour. This implies that the presence of a lethal concentration of a drug in
      just one sample of heart blood can prove worthless in a case where agonal drug
      infusion may have occurred.

PMID- 9544548
TI  - Considerations in the interpretation of urine analyses in suspected opiate
      intoxications.
AB  - Over the years, it has been observed that in many suspected opiate intoxications,
      a urine screen using the standard 300 ng/mL cutoff has produced negative results.
      Subsequent analysis of the blood in many of these cases, in fact, were positive
      for morphine. To identify the frequency of this occurrence and to determine a
      more appropriate urine screening cutoff, paired blood and urine specimens were
      tested for opiates at the above cutoffs. Over the 6 months period of this study,
      102 cases were identified where the blood morphine concentration by Roche
      Abuscreen was greater than 100 ng/mL of "morphine equivalents." All positive
      cases were confirmed as morphine by gas chromatography-mass spectrometry. Seventy
      nine of these cases, or 77%, had urine concentrations by Abuscreen exceeding 300
      ng/mL of "morphine equivalents." The remaining 23 cases had urine morphine
      concentrations less than 300 ng/mL by Abuscreen. Urine specimens were then
      reanalyzed by Abuscreen using dilutions of the 300 ng/mL calibrator: 50, 75, and
      150 ng/mL. Even with the use of a 50 ng/mL cutoff, 9 of these 23 specimens tested
      negative by Abuscreen. Moreover, 23 of the 67 cases or 34% in which the cause of
      death was narcotic intoxication had urine opiate concentrations by Abuscreen less
      than the recommended 300 ng/mL cutoff. These results indicate the critical
      importance in cases of suspected narcotic intoxication of screening the blood in
      addition to urine.

PMID- 9544549
TI  - Setting cutoff concentrations for immunoassay screening of postmortem blood.
AB  - The objective of this study was to establish the optimum immunoassay cutoff
      concentrations for screening postmortem blood from coroner's cases for drugs of
      abuse with a coated tube radioimmunoassay (RIA) to ensure that the results with
      the coated tube RIA would be equal to or better than those with the previously
      used double antibody RIA. Immunoassay results (positive or negative) blood were
      compared to confirmed results on those cases by GC/MS alone or in combination
      with GLC using either a NPD or FID detector. Four to seven potential cutoff
      concentrations were evaluated for the drug classes opiates, amphetamines, cocaine
      and metabolites, and barbiturates. Specimens were 350 postmortem blood specimens
      and liver homogenates. The cutoffs chosen for the coated tube RIA using this
      approach were 5 ng/mL morphine, 25 ng/mL methamphetamine, 500 ng/mL
      benzoylecgonine, and 500 ng/mL secobarbital. These cutoffs corresponded to a
      sensitivity and specificity of 94% and 96% for opiates, 93% and 86% for
      amphetamines, 91% and 96% for cocaine and metabolites and 91% and 87% for
      barbiturates. The double antibody RIAs were run on the same specimens with
      cutoffs of 20 ng/mL morphine, 50 ng/mL methamphetamine, 50 ng/mL benzoylecgonine
      and 1000 ng/mL phenobarbital. The sensitivity and specificity's for the double
      antibody immunoassay were: > 99% and 96% for opiates, 83% and 89% for
      amphetamines, 98% and 97% for cocaine, 79% and 95% for barbiturates.

PMID- 9544550
TI  - Evaluation of the accuracy of on-site multi-analyte drug testing devices in the
      determination of the prevalence of illicit drugs in drivers.
AB  - A principal goal of this research was to conduct a field evaluation of "on-site"
      multi-analyte drug testing devices to determine the most accurate, efficient, and
      cost-effective device available for the purpose of rapidly detecting drivers
      under the influence of drugs. Four on-site kits were selected and evaluated for
      accuracy and efficiency for the detection of tetrahydrocannabinol (THC), the
      cocaine metabolites (COC), and opiates (OPI). From 16 December 1995 to 17 March
      1996, 303 voluntary urine specimens were collected by law enforcement officers
      from persons arrested for driving-under-the-influence (DUI). These specimens were
      tested using the four selected kits and aliquots of the specimens were sent to a
      DHHS certified lab for "gold standard" comparison testing by immunoassay and Gas
      Chromatography/Mass Spectrometry. On-site kit sensitivity ranged from 82.9% to
      100% for THC, 82.5% to 100% for COC, and all were at 100% for OPI. Specificity,
      and positive and negative predictive values were also determined. Accuracy ranged
      from 94.0% to 98.3% for THC, 97.4% to 98.0% for COC, and 99.7% to 100% for OPI.
      All four kits were in very close agreement on prevalence: 15.5% to 15.8% for THC,
      all were at 13.2% for COC, and all were at 0.7% for OPI. For law enforcement
      purposes, sensitivity may be the most important indicator in these kits.

PMID- 9544551
TI  - Xylazine toxicity--literature review and report of two cases.
AB  - Xylazine is a veterinary sedative, analgesic or general anesthetic. Its
      pharmaceutical action results in sympathetic discharge via stimulation of alpha-2
      adrenoceptors. In humans, toxicity consists of central nervous system depression,
      bradycardia and hypotension. The dosages known to produce toxicity in humans vary
      from 40 mg up to 2400 mg. Because of decomposition, xylazine blood concentrations
      in two homicide victims were unknown; however, the concentrations in the brain,
      liver, and kidneys were much higher in the 23-year-old female versus the 33-year
      old male victim. A bottle of xylazine found on the crime scene had a
      concentration of 100 mg/mL. This 50 mL bottle had 32 mL remaining. Therefore at
      some point in time 18 mL had been utilized. The amount of available milligrams of
      xylazine (1800 mg) were enough to cause toxicity in both the woman and the man.
      Of interest was the fact that the partially skeletonized heads were found remote
      from the torsos, however, the concentration of xylazine in the body tissues
      provided a toxicological match of which head belonged to which body. Xylazine
      toxicity in humans and its relationship to these homicides will be the focus of
      this report.

PMID- 9544552
TI  - Quechua Amerindian population characterized by HLA-DQ alpha, YNZ22, 3'APO B,
      HUMTH01, and HUMVWA31A polymorphisms.
AB  - Allele and genotype frequencies of DNA polymorphisms were determined in a
      population sample of Quechua (n = 113) using the polymerase chain reaction (PCR).
      We report data on the frequencies of HLA-DQ alpha, YNZ22, 3'ApoB, HUMTH01 and
      HUMVWA31A alleles and the distribution of the different genotypes. No significant
      deviations between observed and expected numbers were found, thus assuming the
      Hardy-Weinberg equilibrium.

PMID- 9544553
TI  - D4S43 locus DNA typing in the Japanese population and application to teeth with
      degraded DNA.
AB  - VNTR polymorphism at the D4S43 locus was investigated, and allele frequencies in
      the Japanese population sample were determined by the polymerase chain reaction.
      Eleven different alleles and 16 genotypes were observed in 131 unrelated
      Japanese. The most common allele was one repeat unit (60.3%), the heterozygosity
      index of the present study was 58.7%, and the polymorphic information content was
      calculated at 0.55. In addition, we found four new size variations in the one
      repeat-unit allele, which was the most common allele among the Japanese
      population. These variations were believed to be different from variations by
      repeats of the basic 14-bp unit. The one-repeat-unit allele at the D4S43 locus,
      which comes in four sizes, was detected in all of the samples, including degraded
      DNA samples obtained from hard tooth tissue. Therefore, this new variation is
      useful in personal identification by DNA analysis using forensic scientific
      degraded DNA samples.

PMID- 9544554
TI  - The DRPLA CAG repeats in an Italian population sample: evaluation of the
      polymorphism for forensic applications.
AB  - The DRPLA CAG repeats polymorphism has been studied in an Italian population
      sample. PCR amplification, manual PAGE and silver staining were employed. A total
      of 16 different alleles, spanning the range from 5 to 21 CAG triplettes, was
      observed. The heterozygosity was 0.81 and no significant deviation from Hardy
      Weinberg equilibrium was found 81 meioses from parentage testing were also
      analyzed and a Mendelian pattern of inheritance was observed in all cases. In
      addition, we could successfully type DRPLA locus in some forensic specimens, 1 ng
      of DNA allowing clear definition of alleles. The authors conclude that the DRPLA
      CAG repeats analysis may be useful for forensic applications.

PMID- 9544555
TI  - Human orosomucoid (ORM1) subtyping: further population genetic data and reports
      on the feasibility to type aged blood samples and stains.
AB  - Genetic polymorphism of serum orosomucoid (ORM1) was investigated in 1072
      unrelated German Caucasians using isoelectric focusing followed by Western
      blotting and EIA. The estimated allele frequencies were ORM1 *F1 = 0.5690, ORM1
      *S = 0.3927, ORM1 *F2 = 0.0368, ORM1 *F2S = 0.0009 and ORM1 *F5 = 0.0005. The
      method was successfully applied to determine ORM1 phenotypes in aged blood
      samples and blood stains. The results indicated that the ORM protein is a
      informative and remarkably robust blood group system.

PMID- 9544556
TI  - Experimental single controlled study of burned bones: contribution of scanning
      electron microscopy.
AB  - Burned bones were studied using Scanning Electron Microscopy. The samples were
      cut from a maxillary-mandibular block taken during an autopsy. These fragments
      were heated in a furnace under controlled temperature conditions for 60 minutes.
      The temperatures ranged from 150 to 1150 degrees Celsius. The results are as
      following: (i) there are significant alterations of the bone, more and more
      obvious as the temperature increases, (ii) it appears to be difficult to
      establish a precise correlation between the temperature and the scanning electron
      microscopy patterns.

PMID- 9544557
TI  - Analysis of shrinkage in human fetal diaphyseal lengths from fresh to dry bone
      using Petersohn and Kohler's data.
AB  - Calculation of gestational age from forensic fetal remains may be problematic. If
      soft-tissue indicators are not available, then diaphyseal lengths obtained
      through sonograms on living fetuses in utero or radiographs of long bones can be
      compared to known European standards, such as Fazekas and Kosa (1978) and Olivier
      and Pineau (1958, 1960). Radiographic comparison to these European standards,
      however, requires a correction factor for diaphyseal shrinkage from fresh to dry
      states. Percent shrinkage is calculated for six diaphyses (humerus, ulna, radius,
      femur, tibia and fibula) from Petersohn and Kohler's data published in Fazekas
      and Kosa (1978:362-369). Average shrinkage, standard deviation, minimum and
      maximum values are calculated for each diaphysis and for all diaphyses during 4
      10 lunar months (LM) and newborns. Corresponding average and standard deviation
      values are as follows: 4 LM-10.09% +/- 2.67%; 5 LM-5.74% +/- 0.84%; 6 LM-3.48% +/
      0.49%; 7 LM-2.32% +/- 0.16%; 8 LM-2.18% +/- 0.51%; 9 LM-1.76% +/- 0.14%; 10 LM
      1.90% +/- 0.59%; and newborns-1.28% +/- 0.55%. Analysis of these values suggests
      that percent shrinkage steadily declines as the fetus ages. This pattern
      presumably reflects calcification of bone during growth and development in utero.
      These findings demonstrate a significant shrinkage in the diaphysis early in
      development, which may alter accurate age estimation in the earliest fetal age
      groups.

PMID- 9544558
TI  - Correlation of body mass index with thoracic and abdominal panniculus.
AB  - Obesity can play a significant role in chronic diseases, sudden unexpected death,
      and morbid obesity may be important as a cause of death for forensic
      pathologists. Our study attempted to determine if there is a correlation between
      panniculus measurements and body mass index (BMI) since BMI has been used in most
      studies to categorize obesity. Using data obtained from a review of 524 adult
      autopsies conducted at the University of Michigan from 1990 to 1992 we were able
      to show a correlation between both thoracic and abdominal panniculus and BMI (r2
      = 0.335 and 0.296 respectively) which is statistically significant (p = 10(-47)
      and 10(-41) respectively). A prospective study confirmed the correlation (r2 =
      0.552 for thoracic and 0.436 for abdominal panniculus) when the measurements were
      taken at the xyphoid process and 3 cm below the umbilicus. Using these data we
      calculated a panniculus index (PI) which is equal to the thoracic + abdominal
      panniculus in centimeters divided by the square of the height (in meters). The PI
      strongly correlated with BMI and was able to predict obesity. Using a BMI cutoff
      of 39 for morbid obesity, a PI value of 4.07 for females and 3.25 for males
      predicted morbid obesity with the probability of a false positive less than or
      equal to 2.5%. Mild and severe obesity could also be determined using the PI.
      Based on these data we've concluded that a concise mathematical relationship does
      exist between BMI and panniculus measurements. Therefore panniculus measurements
      can be used either as a surrogate measurement of morbid obesity or to support BMI
      calculations.

PMID- 9544559
TI  - Origin and gender determination of dried blood on a statue of the Virgin Mary.
AB  - In Italy, blood exudation from objects of worship recurs frequently in ancient
      chronicles and literature, in popular beliefs, and even in modern mass-media
      reports. This phenomenon, that was associated with epochal or catastrophic
      events, has roots that reach classical antiquity. In the last few years, several
      events connected with the detection of bloody "tears" on statues of the Virgin
      Mary required forensic medicine investigations. In the present report we describe
      genetic investigations conducted on dried blood of unknown derivation found on a
      statuette representing the Virgin Mary. To test the human or animal origin of the
      blood, we amplified Alu-specific sequences from DNAs obtained from the unknown
      sample and from humans, large apes, various Old and New World monkeys, a
      prosimian, mouse, common domestic artiodactyls and chicken. This investigation
      restricted the range of possible origin of the statue blood to humans, apes and
      Old World monkeys. To test the male or female origin of the blood, we used a
      multiplex nested polymerase chain reaction method, that allows the simultaneous
      amplification of the X-specific locus DXZ4 and of the Y-specific locus SRY.
      Considering the unlikelihood of an origin from simian Old World primates, the
      exclusive amplification of the X-specific product from the unknown sample and
      from human female blood controls, compared to the amplification of distinct X-
      and Y-specific bands from human male blood controls, strongly supports a human
      female origin of the statue blood.

PMID- 9544560
TI  - Evidence of polydrug use using hair analysis: a fatal case involving heroin,
      cocaine, cannabis, chloroform, thiopental and ketamine.
AB  - A case is presented involving a young woman on several illicit drugs (heroin,
      cocaine and cannabis) as well as two medications and a solvent used for their
      anesthetic and narcotic properties: thiopental, ketamine and chloroform. This
      complex drug use was supported by hair analysis over a 10.5 cm segment of the
      hair taken at autopsy. The average measured concentrations in hair were:
      thiopental = 5.3 ng/mg, pentobarbital = 10.0 ng/mg, ketamine = 11.3 ng/mg
      norketamine = 1.0 ng/mg, diazepam = 1.2 ng/mg, nordiazepam = 0.1 ng/mg, 6
      acetylmorphine = 4.4 ng/mg, morphine = 3.4 ng/mg, codeine = 1.2 ng/mg, cocaine =
      5.5 ng/mg, benzoylecgonine = 1.5 ng/mg and methylecgonine ester = 1.0 ng/mg.
      While the ketamine/norketamine ratio is consistent with that already reported on
      drug detection in hair, the thiopental/pentobarbital ratio seems to be inverted.

PMID- 9544561
TI  - Croton ruizianus: platelet proaggregating activity of two new pregnane
      glycosides.
AB  - The MeOH extract of the aerial parts of Croton ruizianus afforded two new
      pregnane glycosides 1 and 2, together with the morphinandienone alkaloids
      flavinantine (3) and O-methylflavinantine (4). Their structures were elucidated
      by NMR experiments including 1H-1H (1D TOCSY and 2D DQF-COSY) and 1H-13C (HSQC,
      HMBC) spectroscopy. The proaggregating activity of the MeOH extract and the
      isolates were evaluated. Although the MeOH extract and pregnane glycosides (at
      different doses) were found to promote platelet aggregation, flavinantine (3) and
      O-methylflavinantine (4) showed only slight activity. The ability of the MeOH
      extract and the four compounds to act synergistically with thrombin was also
      evaluated. All the tested compounds were successful in augmenting the aggregating
      effect of thrombin, although to different degrees.

PMID- 9544562
TI  - Triterpenoid saponins from Spergularia ramosa.
AB  - Six new oleanene glycosides were isolated from the MeOH extract of the aerial
      parts of Spergularia ramosa. They possess gypsogenin or quillaic acid as the
      aglycons. The disaccharide moiety linked to C-3 of the aglycons is made up of
      galactose (or glucose) and glucuronic acid (or glucose); the pentasaccharide
      moiety linked to C-28 is made up of glucose (or galactose), xylose, rhamnose,
      fucose, and arabinose. Their structures were elucidated by 1D and 2D NMR
      experiments including 1H-1H (DQF-COSY, 1D TOCSY, 2D HOHAHA, ROESY) and 1H-13C
      (HSQC, HMBC) spectroscopy.

PMID- 9544563
TI  - Cardiovascular effects of aspidofractinine-type alkaloids from Kopsia.
AB  - Intravenous injection of the aspidofractinine alkaloid, kopsingine (1, 0.2-10.0
      mg/kg) from Kopsia teoi, produced dose-related decreases in the mean arterial
      blood pressure and heart rate in anesthetized spontaneously hypertensive rats,
      which were similar to those seen in normotensive controls. Minor modifications in
      the molecular structure of kopsingine, as in kopsaporine (2, the 12-demethoxy
      derivative of kopsingine) and 14,15-dihydrokopsingine (4), did not significantly
      alter the hypotensive responses, whereas a more drastic change in the structure,
      as in the heptacyclic kopsidine A (3) and the 3-to-17 oxo-bridged compound 5,
      resulted in an increase in blood pressure. The antihypertensive effects of
      kopsingine (1) and its congeners (2 and 4) along with the pressor effects
      produced by the heptacyclic oxo-bridged compounds (5 and 3) could be ascribed to
      central as well as peripheral actions.

PMID- 9544564
TI  - 5-Lipoxygenase and cyclooxygenase-1 inhibitory active compounds from Atractylodes
      lancea.
AB  - Lipophilic extracts of Atractylodes lancea rhizomes exhibited potent inhibitory
      activities in 5-lipoxygenase [IC50 (5-LOX) = 2.9 micrograms/mL (n-hexane
      extract)] and cyclooxygenase-1 [IC50 (COX-1) = 30.5 micrograms/mL (n-hexane
      extract)] enzymatic assays. Bioactivity-guided fractionation of the n-hexane
      extract led to the isolation of a new compound atractylochromene (1), a potent
      inhibitor in both test systems [IC50 (5-LOX) = 0.6 microM, IC50 (COX-1) = 3.3
      microM]. Also obtained was 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2,5
      cyclohexadiene-1 ,4-dione (2), which showed a selective inhibitory activity
      against 5-LOX [IC50 (5-LOX) 0.2 microM, IC50 (COX-1) 64.3 microM]. The
      sesquiterpene atractylon (3) and the coumarin osthol (4) turned out to be
      moderate but selective 5-lipoxygenase inhibitors. Atractylenolides I (5), II (6),
      and III (7) showed no significant inhibitory effects for either enzyme.
      Structures were established by spectral data interpretation.

PMID- 9544565
TI  - HIV-inhibitory and cytotoxic oligostilbenes from the leaves of Hopea malibato.
AB  - Three new oligostilbenes, malibatols A (1) and B (2) and dibalanocarpol (3),
      together with one known oligostilbene balanocarpol (4), were isolated from the
      organic extract of the leaves of Hopea malibato. The structure elucidation of
      these compounds was based on the interpretation of their chemical and spectral
      data. Compounds 3 and 4 exhibited very modest HIV-inhibitory activity, while
      compounds 1 and 2 were cytotoxic to the host cells (CEM SS) in the antiviral
      assay.

PMID- 9544567
TI  - New imidazole alkaloids and zinc complexes from the micronesian sponge Leucetta
      cf. chagosensis.
AB  - Four new imidazole alkaloids, 2-5, along with the known isonaamidine B (1) were
      isolated from a Pacific sponge, Leucetta cf. chagosensis, collected from Yap,
      Federated States of Micronesia. Among these, 4 and 5 are zinc complexes derived
      from isonaamidine B and isonaamidine D. The structures of the new compounds were
      elucidated from spectral data. Isonaamidine D (3) showed weakly antifungal
      activity against Aspergillus niger with MIC = 100 micrograms/mL.

PMID- 9544566
TI  - DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia.
AB  - An ethanol extract of Psoralea corylifolia caused strong DNA polymerase
      inhibition in a whole cell bioassay specific for inhibitors of DNA replication
      enzymes. Bioassay-directed purification of the active compounds led to the
      isolation of the new compound corylifolin (1) and the known compound bakuchiol
      (2) as DNA polymerase inhibitors. On the basis of the structures of 1 and 2,
      resveratrol (3) was tested and found to be active as a DNA polymerase inhibitor
      in this bioassay. Neobavaisoflavone (4) was isolated as a DNA polymerase
      inhibitor, daidzein (5) as a DNA polymerase and topoisomerase II inhibitor, and
      bakuchicin (6) as a topoisomerase II inhibitor.

PMID- 9544568
TI  - Antihyperglycemic effects of N-containing sugars from Xanthocercis zambesiaca,
      Morus bombycis, Aglaonema treubii, and Castanospermum australe in streptozotocin
      diabetic mice.
AB  - The aqueous MeOH extract of the leaves and root of Xanthocercis zambesiaca
      (Leguminosae) and eight structurally related nitrogen-containing sugars, fagomine
      (1), 4-O-beta-D-glucopyranosylfagomine (2), 3-O-beta-D-glucopyranosylfagomine
      (3), 3-epifagomine (4), 2,5-dideoxy-2,5-imino-D-mannitol (5), castanospermine
      (6), alpha-homonojirimycin (7), and 1-deoxynojirimycin (8) were evaluated for
      antihyperglycemic effects in streptozotocin (STZ)-diabetic mice. The insulin
      releasing effects of 1 were also investigated. The blood glucose level fell after
      i.p. injection of the extract (50 mg/kg). Compounds 1, 2, 5, and 6 reduced the
      blood glucose level after i.p. injection of 150 mumol/kg. Compound 1 increased
      plasma insulin level in STZ-diabetic mice and potentiated the 8.3-mM glucose
      induced insulin release from the rat isolated-perfused pancreas. The 1-induced
      potentiation of insulin release may partly contribute to antihyperglycemic
      action.

PMID- 9544569
TI  - Pseudopterane and norcembrane diterpenoids from the Caribbean sea plume
      Pseudopterogorgia acerosa.
AB  - A chemical study of the common Caribbean sea plume Pseudopterogorgia acerosa from
      Puerto Rico has produced two previously undescribed secondary metabolites. One of
      them, 1, is a new representative of the pseudopterane family of diterpenes
      possessing the uncommon 3,4;5,6 diepoxyfuran moiety. The other metabolite, 2, is
      a rare norcembranolide diterpene. Their chemical structures, including relative
      stereochemistry, were established by detailed analysis of the spectral data in
      addition to NMR spectral comparisons with known pseudopterane and cembrane
      models.

PMID- 9544570
TI  - Transcription factors that regulate monocyte/macrophage differentiation.
AB  - Although all the cells in an organism contain the same genetic information,
      differences in the cell phenotype arise from the expression of lineage-specific
      genes. During myelopoiesis, external differentiating signals regulate the
      expression of a set of transcription factors. The combined action of these
      transcription factors subsequently determines the expression of myeloid-specific
      genes and the generation of monocytes and macrophages. In particular, the
      transcription factor PU.1 has a critical role in this process. We review the
      contribution of several transcription factors to the control of macrophage
      development.

PMID- 9544571
TI  - The role of CD40/CD154 interactions in the priming, differentiation, and effector
      function of helper and cytotoxic T cells.
AB  - This review focuses on the emerging body of literature suggesting a critical role
      for CD40/CD154 interactions in antigen-presenting cell (APC) activation, CD4+ and
      CD8+ T cell priming, and effector T cell maturation. In this context effective
      antigen presentation involves not only T cell expansion and long-term survival
      but also the ability of the APC to guide the T cell response toward the Th1
      (interferon-gamma producing) or the Th2 (interleukin-4 producing) phenotype. We
      suggest a model to explain why CD40/CD154 interactions are critical for some
      helper and cytotoxic T cell responses, whereas others occur independently of this
      receptor/ligand pair. In addition, we will discuss the potential role for
      CD40/CD154 interactions in effector T cell maturation and cytokine production.

PMID- 9544572
TI  - Trypanosoma brucei infection elicits nitric oxide-dependent and nitric oxide
      independent suppressive mechanisms.
AB  - During murine Trypanosoma brucei infection, macrophages contribute significantly
      to the inhibition of T cell responses. Although nitric oxide (NO) was shown to
      play a central role in macrophage-mediated splenic suppression, macrophage
      mediated lymph node suppression occurred in an interferon-gamma (IFN-gamma)
      dependent manner. In this study, using NO inhibitor NG-monomethyl-L-arginine and
      anti-IFN-gamma antibodies, the relative contribution of NO and IFN-gamma to the
      active inhibition of ex vivo concanavalin A-induced T cell proliferation taking
      place in the spleen and the lymph nodes of T. brucei-infected mice was
      investigated. NO contributes to the suppressive activity of spleen and lymph node
      cells only during early-stage infection. The existence of NO-independent
      suppressive pathway was further evidenced in IFN-gamma(-/-)-infected mice. Spleen
      cells from such animals do not produce NO but exert significant suppressive
      activity during the whole course of infection. In contrast in the lymph nodes, no
      suppressive activity is recorded at any moment of infection. Moreover, addition
      of exogenous IFN-gamma to cultures containing lymph node cells from IFN-gamma(-/
      )-infected mice does not impair proliferation despite NO production in such
      cultures. Thus during late-stage infection, an IFN-gamma-independent suppressive
      mechanism is elicited in the spleen, whereas in the lymph nodes, IFN-gamma is
      required yet not sufficient to inhibit T cell proliferation.

PMID- 9544573
TI  - Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal
      tuberculous (BCG) lesions.
AB  - To our knowledge, this is the first sequential study of cytokines in tissue
      sections of developing and healing tuberculous (BCG) lesions. In situ
      hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine
      mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN)
      containing IL-1beta, TNF-alpha, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day
      lesions, apparently because of the nonspecific inflammatory response caused by
      the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was
      significantly reduced. With IFN-gamma, the peak and trough were delayed by 2
      days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines
      had again increased and the rabbits had become tuberculin-positive. In general,
      MCP-1 and TNF-alpha proteins and the vascular adhesion molecules, ICAM, VCAM, and
      perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the
      central areas of solid and liquefied caseous necrosis contained chemokine IL-8
      mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN
      containing chemokine MCP-1 mRNA were present more peripherally in areas rich in
      macrophages and lymphocytes. The early nonspecific cytokine response seems to be
      an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid
      entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells
      into local sites of antigen deposition. This effect should be considered in
      developing improved vaccines for the prevention of tuberculosis, because BCG
      vaccines producing a strong early cytokine response should be more immunogenic
      than BCG vaccines with similar antigens producing a weak response.

PMID- 9544574
TI  - Collagenase expression by normal human eosinophils.
AB  - Collagenolytic activity was detected in extracts from human blood eosinophilic
      granulocytes. To characterize this collagenase, we compared extracts from
      isolated populations of eosinophils and neutrophils. Significant collagenase
      activity against type I and II collagens was present in extracts from both cell
      populations. Although collagenase activity was present in eosinophils, the cells
      did not stain with antibodies specific for fibroblast, neutrophil collagenase, or
      collagenase-3. In contrast, neutrophils immunostained positively with antibody to
      neutrophil collagenase. Western blot analysis confirmed the presence of
      immunoreactive protein in neutrophil extracts but not in the eosinophil extracts.
      Reverse transcription-polymerase chain reaction using primers specific for all
      three known collagenases of an eosinophil cell suspension from peripheral blood
      that had 3% contamination with immature neutrophils showed a polymerase chain
      reaction product only with neutrophil collagenase oligonucleotide primers, but
      not with fibroblast collagenase or collagenase-3 primers. Eosinophil collagenase
      would appear to have a unique antigenic structure and may represent a new enzyme.

PMID- 9544575
TI  - Processing of C5a by human polymorphonuclear leukocytes.
AB  - Uptake of human C5a by neutrophils was monitored in vitro using both 125I-labeled
      and unlabeled C5a. The ligand was internalized by the cells in a dose-dependent
      manner and maximal binding/uptake was observed after 5 min of incubation.
      Neutrophils were incubated with labeled C5a and the cytosol and supernatant were
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      autoradiography. C5a degradation products were primarily observed in the
      supernatant, whereas most of the protein remained intact in the cytosol even
      after 60 min of incubation. Cytosol from neutrophils incubated for 20 min with
      unlabeled C5a was examined by radioimmunoassay and found to contain antigenically
      intact C5a and retained the ability to induce a neutrophil (shape change)
      response. The functional activity of C5a recovered from the cytosol was inhibited
      by antibodies to either C5a or the C5a receptor (CD88). This data supports our
      hypothesis that although C5a is internalized it remains antigenically intact and
      functionally active inside the cell and is primarily degraded extracellularly.

PMID- 9544576
TI  - HIV-1 induces human monocyte-derived macrophages to produce C3 and to fix C3 on
      their surface.
AB  - Complement components, particularly C3, are known to be involved in the
      pathogenesis of AIDS and macrophages may serve as a source of C3 at sites of
      infection. We investigated whether the interaction between HIV-1 and monocytes
      has any effect on C3 production by the cells. Monocytes isolated from the blood
      of healthy volunteers were incubated with monocytotropic and T lymphocytotropic
      HIV-1 strains or with recombinant gp160 and cultured in serum-free medium up to 7
      days. Supernatants were tested for secreted C3 by enzyme-linked immunosorbent
      assay. Our data show that monocytes cultured with either the monocytotropic or
      the T lymphocytotropic HIV-1 strains produce C3 in large amounts. The effect of
      both viruses is dose dependent and the amount of C3 induced by HIV was up to 20
      fold higher than in the control samples. C3 production was also enhanced by
      gp160, the envelope protein of the virus. Secretion of IL-6 by the cells was also
      measured and found to be elevated up to threefold as a consequence of the
      interaction with the virus. HIV-1-activated monocyte-derived macrophages acquired
      the capacity to cleave exogenous C3 and to fix generated C3 fragments on their
      cell membrane.

PMID- 9544577
TI  - Platelets induce monocyte differentiation in serum-free coculture.
AB  - Terminal maturation of blood monocytes (MO) in vitro and in vivo into macrophages
      (MAC) occurs as a result of interactions with various cell types. To characterize
      some of the cell-cell connections that may be important for MO differentiation we
      cocultured human MO with lymphocytes and/or with platelets. We found that intact
      platelets strongly promoted MO maturation under serum-free conditions as evident
      from the expression of differentiation-dependent antigens and morphology. To
      further characterize the differentiation-inducing component(s) we prepared
      membrane and cytosol fractions of platelets. Both fractions could induce MO
      maturation, comparable to intact platelets. Further centrifugation of the
      cytosolic fraction revealed that only the pellet of ultracentrifugation, e.g.,
      membrane fragments, could induce MO differentiation. Digestion with either
      trypsin or neuraminidase could only partially inhibit this effect. The same was
      true for heat-treated fractions, indicating that this platelet-derived
      differentiation stimulus is not solely an intact protein. Next we prepared
      protein and lipid fractions of platelets. Treatment of MO with platelet proteins
      or platelet lipids clearly showed that only the lipid components were able to
      induce MO maturation. We propose components present in the lipid fraction of
      platelet membranes as possible inducers of MO maturation in vitro.

PMID- 9544578
TI  - Ligation of CR1 attenuates Fc receptor-mediated myeloperoxidase release and HOCl
      production by neutrophils.
AB  - Surface adherent immunoglobulins are potent stimuli for inducing neutrophil
      release of myeloperoxidase and production of hypochlorous acid (HOCl), an oxidant
      that promotes activity of neutrophil proteases. Opsonization of surface adherent
      IgG (SAIgG) by complement results in attenuation of these responses, despite
      augmenting neutrophil production of superoxide and release of specific granule
      enzymes. The role of complement receptor ligation in modulating Fc receptor
      triggered myeloperoxidase release and HOCl production by neutrophils was
      determined by incubating neutrophils with SAIgG in the presence of complement
      receptor ligating antibody reagents. Ligation of CR1 by F(ab')2 derived from CR1
      specific monoclonal antibody (mAb 543) resulted in significant attenuation of
      surface-associated IgG (SAIgG)-induced release of myeloperoxidase and HOCl
      production but did not result in attenuation of SAIgG-induced superoxide or
      hydrogen peroxide production; ligation of CR1 by mAb 543 F(ab')2 also attenuated
      surface adherent IgA-induced myeloperoxidase release and HOCl production. HOCl
      production was not significantly attenuated when neutrophils were activated with
      SAIgG in the presence of surface adherent C1q or when CR3 was ligated by F(ab')2
      derived from mAb having specificity for the CD11b (mAb M1/70) or CD18 (mAb TS1)
      subunits of CR3. These results indicate that ligation of CR1 on neutrophils by
      C3b fixed to IgG may alter signal transduction events linking ligation of
      neutrophil Fc receptors to cellular events required for release of
      myeloperoxidase and generation of HOCl.

PMID- 9544579
TI  - Chemokine synthesis in the HSV-1-infected cornea and its suppression by
      interleukin-10.
AB  - Herpes simplex virus type 1 (HSV-1) infection of the murine cornea results in a
      tissue-destructive inflammatory response. In this study we show that virus
      infection induces the synthesis of macrophage inflammatory protein-2 (MIP-2), MIP
      1alpha, and monocyte chemoattractant protein-1 (MCP-1). However, only the
      production of MIP-2 and MIP-1alpha coincided with the influx of leukocytes into
      the cornea. IL-10 treatment markedly suppressed chemokine message and protein
      synthesis in vivo. Local administration of IL-10 also dramatically reduced the
      number of T cells and neutrophils migrating into the cornea and suppressed the
      severity of corneal disease. The inflammatory response could also be suppressed
      by the passive transfer of neutralizing antibody to MIP-1alpha but not MCP-1. We
      conclude that local IL-10 administration can suppress chemokine synthesis,
      thereby ameliorating corneal disease. Furthermore, our results indicate that MIP
      1alpha plays a major role in herpes stromal keratitis development, whereas MCP-1
      does not.

PMID- 9544580
TI  - Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease
      activities and phases of human IgA nephropathy.
AB  - Leukocytes have been implicated to be involved in the pathogenesis of IgA
      nephropathy (IgAN). To clarify the precise molecular mechanism of recruitment and
      activation of leukocytes in the subgroups of IgAN, latent, acute, and chronic
      types, we studied monocyte chemotactic and activating factor (MCAF/MCP-1) and
      interleukin (IL)-8 in urines and renal expression of these cytokines. Urinary
      MCAF levels were significantly higher in chronic type, and were correlated with
      pathological progressive factors such as mesangial proliferation and interstitial
      cellular infiltration associated with CD68-positive macrophage. On the other
      hand, urinary IL-8 elevated only in acute type and were correlated with
      glomerular endocapillary proliferation and the degree of hematuria. In
      immunohistochemical study, IL-8 was mainly observed in glomeruli, otherwise MCAF
      in vascular endothelial cells, tubular epithelial cells, and infiltrated
      mononuclear cells in the interstitial lesions. These observations demonstrated
      that MCAF and IL-8 were differentially expressed in kidneys with IgAN, and their
      subtypes, and suggest that chemokines may be involved in the pathogenesis of IgAN
      at distinct phases or pathological lesions, possibly through the recruitment and
      activation of a distinct type of leukocyte.

PMID- 9544581
TI  - Modulation of neutrophil adherence to endothelial cells by platelet-derived
      adherence-inhibiting factor through interactions with selectin molecules.
AB  - Platelet-derived adherence-inhibiting factor (AIF) has been demonstrated to
      regulate the neutrophil binding to type IV collagen. In this study, we have
      examined the effect of AIF on neutrophil adherence to confluently cultured human
      umbilical vein endothelial cells (EC). AIF inhibited neutrophil adherence to
      thrombin- or tumor necrosis factor alpha (TNF-alpha)-stimulated EC by 75 or 43%,
      respectively, but hardly affected neutrophil adherence to resting EC. It is
      interesting to note that the inhibitory activity of AIF was reduced by N-formyl
      methionyl-leucyl-phenylalanine (fMLP) stimulation of neutrophils. Pretreatment of
      neutrophils or EC with AIF inhibited neutrophil adherence to thrombin- or TNF
      alpha-stimulated EC, suggesting that neutrophils and EC have AIF-binding
      proteins. Using AIF-Sepharose affinity chromatography, AIF-binding proteins
      containing L-selectin were isolated from 125I-labeled resting neutrophils.
      However, L-selectin was markedly decreased in the AIF-binding fraction from fMLP
      stimulated neutrophils. With the use of AIF-affinity chromatography, P- and E
      selectins were obtained in the AIF-binding fractions from resting, thrombin-, and
      TNF-alpha-stimulated EC. It is important to note that P- and E-selectin were
      greatly increased in the AIF-binding fractions from thrombin- and TNF-alpha
      stimulated EC, respectively. Furthermore, AIF was able to bind to L-selectin-IgG
      chimeric protein and inhibit the binding of chimeric protein to thrombin or TNF
      alpha-stimulated EC. In addition, AIF inhibited the binding of anti-P- or anti-E
      selectin monoclonal antibody to the lysates of thrombin- or TNF-alpha-stimulated
      EC. Together these observations indicate that AIF could recognize L-, P-, and E
      selectins, and modulate neutrophil adherence to EC through interactions with
      selectin molecules.

PMID- 9544582
TI  - Inhibition of LPS-mediated activation in rat Kupffer cells by N-acetylcysteine
      occurs subsequent to NF-kappaB translocation and requires protein synthesis.
AB  - Activation of the resident hepatic macrophage population, Kupffer cells, leads to
      production of mediators that initiate, potentiate, and modulate hepatic injury.
      Recent studies have shown that activation of the pluripotent transcription factor
      nuclear factor-kappaB (NF-kappaB) is an important step in the induction of
      inflammatory cytokines, chemokines, growth factors, cell adhesion proteins, and
      cytokine receptors, thus efforts have been focused to modulate its activity. A
      common observation in diverse experimental systems is that oxidant stress
      activates NF-kappaB and antioxidant drugs prevent activation and subsequent
      inflammatory gene transcription. However, we have recently shown that the
      inhibitory effect of N-acetylcysteine (NAC) is independent of its role as a
      substrate of glutathione synthesis and NAC can inhibit Kupffer cell activation at
      points beyond the initiation of activation. The goal of this study was to
      characterize the mechanism for NAC-mediated inhibition of Kupffer cell
      activation. We show for the first time that this process requires a cellular
      synthetic response to prevent both NF-kappaB and tumor necrosis factor alpha (TNF
      alpha) mRNA activation. Furthermore, NAC-mediated inhibition occurs after
      degradation of IkappaB-alpha and nuclear translocation of NF-kappaB. These data
      suggest that inhibition of Kupffer cell activation by NAC is a nuclear event and
      offers a potential approach to modulate Kupffer cell activation during hepatic
      injury.

PMID- 9544583
TI  - Medals, memoirs--and Metchnikoff.

PMID- 9544584
TI  - Mechanisms of neutrophil-induced parenchymal cell injury.

PMID- 9544585
TI  - Methodological inquiries in health status assessment.

PMID- 9544586
TI  - The risk of hospitalization for ischemic stroke among older adults.
AB  - OBJECTIVES: The purpose of this study was to identify risk factors for stroke and
      to estimate their relative importance in a large, nationally representative
      sample of very old men and women. METHODS: The study was designed as a secondary
      analysis of the Longitudinal Study on Aging. Baseline (1984) in-person interview
      data were linked to Medicare hospitalization records for 1984 to 1991.
      Participants were 6,071 noninstitutionalized adults 70 years old or older at
      baseline. Hospitalization for ischemic stroke was defined as having one or more
      episodes with a primary discharge diagnosis containing ICD-9-CM codes of 433.0
      434.9, 436, and 437.0-437.1. Multivariable proportional hazards regression was
      used to estimate the risks associated with previously identified epidemiologic
      factors. RESULTS: Five hundred and three persons (8.3%) had at least one primary
      discharge diagnosis of ischemic stroke. In descending order of importance-based
      on the partial r statistics associated with their adjusted hazards ratios (AHRs),
      the salient risk factors were having a previous history of stroke (AHR = 2.86),
      age (AHR = 1.04 per year), diabetes (AHR = 1.78), male gender (AHR = 1.42), lower
      body limitations (AHR = 1.09 per limitation), arthritis (AHR = 0.74),
      hypertension (AHR = 1.29), and poverty (AHR = 1.33). CONCLUSION: Patients
      presenting with the high risk factors identified in this study should be
      considered for further evaluation and monitoring. Current protocols for the
      therapeutic management of these higher risk patients should be considered, and
      compliance should be encouraged.

PMID- 9544587
TI  - The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a
      community-based analysis.
AB  - OBJECTIVES: The effectiveness of upper endoscopy in unselected patients with
      upper gastrointestinal hemorrhage has not been well studied. This study was
      undertaken to identify factors associated with the performance of early endoscopy
      (ie, within 1 day of hospitalization) and, after adjusting for these factors, to
      determine associations between early endoscopy and in-hospital mortality, length
      of stay, and performance of surgery. METHODS: Subjects in this observational
      cohort study were 3,801 consecutive admissions with upper gastrointestinal
      hemorrhage to 30 hospitals in a large metropolitan region. Demographic and
      clinical data were abstracted from hospital records. A multivariable model based
      on factors that potentially could relate to the decision to perform endoscopy was
      developed to determine the propensity (0 to 100%) for early endoscopy in each
      patient. RESULTS: Early endoscopy was performed in 2,240 patients (59%), and
      although it was not associated with mortality after adjusting for severity of
      illness among all patients, it was associated with a higher risk of death for
      patients in the lowest propensity group. Early endoscopy was associated with a
      lower likelihood of upper gastrointestinal surgery in all patients and in the two
      highest propensity groups and with a shorter length of stay in the entire cohort
      and in all subgroups. CONCLUSIONS: In the absence of specific contraindications,
      early endoscopy should be considered because of associated reductions in length
      of stay and surgical intervention. Further studies are needed to identify
      subgroups in whom the procedure may be associated with adverse effects on
      survival.

PMID- 9544588
TI  - The demand for post-acute and chronic care in nursing homes.
AB  - OBJECTIVES: Nursing homes provide care for persons with both post-acute and
      chronic conditions. In general, these two types of patients are associated with
      short and long stays, respectively. They also tend to be covered by different
      public or private insurance plans. The author investigated whether and how the
      demand for these two types of nursing home care differ. How alternative
      definitions of post-acute and chronic care nursing home stays affect estimates
      also was explored. METHODS: Data on a sample of elderly persons from the National
      Long-Term Care Channeling Demonstration was used. To account for market
      disequilibrium, demand was estimated using a bivariate probit with partial
      observability model. RESULTS: Differences were found in the demand for the two
      types of nursing home care. For instance, economic factors and functional and
      cognitive limitations were relatively more important in the demand for nursing
      home care for chronic conditions. Further, chronic care patients appeared more
      likely to face problems of access into nursing homes. Classifying nursing home
      stays by payer, rather than by length of stay, captured expectations at admission
      and appeared to reflect consumer behavior better. CONCLUSIONS: Differentiating
      post-acute and chronic care nursing home stays provides more meaningful
      information on consumer demand for nursing home care and will facilitate policy
      analysis in this area.

PMID- 9544589
TI  - Comparative responsiveness of generic versus disease-specific and weighted versus
      unweighted health status measures in carpal tunnel syndrome.
AB  - OBJECTIVES: The authors evaluated the relative responsiveness to change of
      generic versus disease-specific and unweighted versus weighted health status
      measures in carpal tunnel syndrome (CTS). METHODS: Data were obtained from 196
      subjects followed in a prospective community-based cohort study in Maine who
      underwent carpal tunnel release (The Maine Carpal Tunnel Syndrome Study).
      Patients were evaluated before and 6 months after surgery. The disease-specific,
      unweighted severity score was derived from the validated Carpal Tunnel Syndrome
      Assessment Questionnaire. Patients were asked to rate the importance of each
      symptom included in the severity score. Each severity question was weighted by
      its importance, creating a disease-specific weighted score. Generic instruments
      were the SF-36, SF-12, and a Quality of Life Rating Scale. Sensitivity to change
      was calculated with the standardized response mean (SRM, mean change/standard
      deviation of change) as well as the effect size (ES, mean change/standard
      deviation of baseline values). The ability of the instruments to distinguish
      clinically important differences was assessed by correlating the changes in
      scores with global ratings on satisfaction and perceived improvement as external
      criteria. RESULTS: The disease-specific weighted score (SRM: 1.56, ES: 1.99) was
      more responsive than the unweighted score (SRM: 1.36, ES: 1.57). The Quality of
      Life Rating Scale, SF-36, and SF-12 subscales were less sensitive to change, with
      standardized response means and effect sizes that ranged from -0.23 to 0.88. The
      ability to distinguish clinically important differences was higher for the two
      disease-specific scales. The coefficients of correlation with the external
      criteria ranged from 0.50 to 0.56 for the unweighted score and 0.56 to 0.62 for
      the weighted score and were significantly stronger than the correlations between
      external measures and the most responsive subscale of the SF-36 (Bodily Pain
      subscale, r = 0.36). The SF-12 health survey performed as well as the SF-36 in
      term of responsiveness and ability to distinguish clinically important change.
      CONCLUSIONS: Disease-specific measures were superior to generic measures in
      capturing clinical change after carpal tunnel release, and a weighted score was
      slightly more responsive than the unweighted score. The SF-12 showed comparable
      psychometric properties compared with the longer 36-item Short-Form Survey.

PMID- 9544590
TI  - Access to public mental health services: determinants of population coverage.
AB  - OBJECTIVES: This study examined factors that affect access to Veterans
      Administration mental health services. METHODS: Data from national Veterans
      Affairs databases and the 1990 Decennial Census were used to estimate rates of
      Veterans Affairs mental health service use in each US county (n = 3,156) among
      all US veterans and in three subpopulations defined by eligibility and clinical
      status. Independent variables examined in standard multivariate analyses and
      using hierarchical linear modeling techniques included county-level
      sociodemographic characteristics (age, race, and income); "unmanaged" service
      system characteristics (those not directly controlled by Veterans Affairs program
      managers, eg, distance from residence to Veterans Affairs and to non-Veterans
      Affairs services, local supply of non-Veterans Affairs services); and "managed"
      service system factors (those directly controlled by Veterans Affairs program
      managers, eg, per capita Veterans Affairs funding level and the efficiency of
      Veterans Affairs service delivery). RESULTS: Altogether, 2.0% of US veterans used
      Veterans Affairs mental health services. More than one third (36%) of the
      variance in utilization was explained by sociodemographic factors; 8% was
      explained by unmanaged service system factors and 7% was explained by managed
      service system factors, with variations among subgroups. Substitution effects
      were demonstrated between Veterans Affairs and non-Veterans Affairs systems and
      appeared to be diagnosis-specific. CONCLUSIONS: Both per capita funding levels
      and efficient service delivery were significantly associated with increased
      access to mental health services. Implications for health system performance
      assessment and management are discussed.

PMID- 9544591
TI  - Outcomes for persons with rheumatoid arthritis with a rheumatologist versus a non
      rheumatologist as the main physician for this condition.
AB  - OBJECTIVE: The authors compared outcomes among persons with rheumatoid arthritis
      (RA) with a rheumatologist versus a non-rheumatologist as the main physician for
      this condition. METHODS: A cohort of 1,025 persons with rheumatoid arthritis were
      followed for as long as 11 years. The principal measures were obtained from an
      annual structured telephone interview conducted by a trained survey worker. All
      persons with rheumatoid arthritis originally were selected from a random sample
      of community rheumatologists, but some subsequently had migrated to the practices
      of non-rheumatologists. The main outcome measures included the number of painful
      and swollen joints, extent of morning stiffness, a global pain rating, functional
      status, and a measure of global improvement. RESULTS: The persons with rheumatoid
      arthritis treated by rheumatologists reported significantly better functional
      status, fewer painful joints, and a lower overall pain rating, although the
      magnitude of these differences was small. A significantly greater proportion of
      the persons with rheumatoid arthritis treated by rheumatologists also reported
      improvement in a global measure of rheumatoid arthritis outcome and simultaneous
      improvement in all outcome measures. On all other outcome measures, the point
      estimate favored those with a rheumatologist as the main rheumatoid arthritis
      physician, although the differences did not reach statistical significance.
      CONCLUSIONS: The evidence suggests an advantage for persons with a rheumatologist
      as the main rheumatoid arthritis physician, but on several of the measures of
      outcome, the magnitude of the advantage was small. Because the present study was
      an observational design, the possibility that the advantage among persons with a
      rheumatologist as the main rheumatoid arthritis physician is an artifact of
      selection bias cannot be ruled out.

PMID- 9544592
TI  - Heterogeneity in the relationship between the time tradeoff and Short Form-36 for
      HIV-infected and primary care patients.
AB  - OBJECTIVES: Evidence in the literature suggests that the overall correlation
      between descriptive and valuational measures of health are weak to moderate. In
      this study, the relationship between descriptive health status measures, obtained
      using the Short-Form 36, and health values, measured with the time tradeoff, was
      explored. METHODS: Two groups of patients matched for age and gender were
      interviewed. One group comprised 139 human immunodeficiency virus (HIV)-infected
      patients; the other group comprised 124 primary care patients. The relationship
      between the SF-36 and the time tradeoff was estimated, assuming homogeneity
      across patients, using multiple regression analysis. Subsequently, the
      relationship was examined assuming heterogeneity across patients and using the
      expectation maximization algorithm in a maximum likelihood context (latent class
      analysis). RESULTS: Four classes, representing 47%, 13%, 8%, and 32% of the
      population, respectively, were found. The overall percentage of variation
      explained under the assumption of a homogeneous relationship was only 33% as
      compared with 85% when heterogeneity was accounted for. Only three
      characteristics (educational level, employment status, and the SF-36 social
      functioning score) sufficed to generate a nearly perfect classification of the
      patients. CONCLUSIONS: Heterogeneity across subjects should be taken into account
      in describing the relationship between health values and health status
      dimensions.

PMID- 9544593
TI  - Functional status transitions and survival in HIV disease: evidence from the AIDS
      Costs and Service Utilization Survey.
AB  - OBJECTIVE: The authors examined the prevalence of limitations in physical
      functioning in a large sample of people with human immunodeficiency virus (HIV)
      infection and the patterns of change in their functional status with time.
      METHODS: Patients receiving treatment for HIV infection were sampled from 26
      providers in 10 cities across the United States; the analytic sample included
      1,784 adults with HIV infection. Functional status was measured three times
      during a 12-month period. Respondents indicated whether they were limited in
      their ability to perform six activities, ranging from vigorous activities to
      bathing and dressing. Responses to the six items were combined to form an index
      of physical functioning. Medical records were used to determine stage of HIV
      infection, and death records were used to determine vital status. Changes in
      functional status during a 1-year period were assessed; correlates of change were
      examined using multinomial logistic regression, with "deceased" included as an
      outcome state. RESULTS: Limitation was most prevalent for vigorous activities
      (55%) and least prevalent for activities of daily living (12%). For each
      activity, the prevalence of limitations rose with increasing disease severity.
      During 1 year, 43% of respondents did not change in functional status, whereas
      42% became worse and 15% reported improved functioning. Controlling for prior
      functional status, multivariate analyses showed that declines in functioning were
      related to developing acquired immunodeficiency syndrome (AIDS), to prior reports
      of fatigue, and to poor self-rated health. These same variables also predicted
      mortality. CONCLUSIONS: Results suggest that the most prevalent types of home
      care assistance needed by those with HIV disease involve help with energy
      demanding activities, such as shopping, and that nonuniform patterns of change in
      functioning necessitate flexible programs to meet frequently changing needs.

PMID- 9544594
TI  - Employer-sponsored health insurance for chiropractic services.
AB  - The use of chiropractors has increased substantially in recent years, and there
      is growing scientific evidence on the effectiveness of chiropractic treatment for
      common low back ailments. Despite the increased acceptance of chiropractic care,
      little is known about the prevalence of chiropractic coverage in employer health
      plans and the nature of such benefits when they are provided. This article
      reports on the extent and composition of chiropractic insurance among workers
      with employer-sponsored health insurance in 1993. The prevalence of the benefits
      in employer plans was examined, as was the extent to which plans are in
      compliance with state mandated benefits in this area. The authors also examined
      what the actual benefits consist of and how they compare with those for physician
      office visits and physical therapy.

PMID- 9544595
TI  - An explanatory model of the dental care utilization of low-income children.
AB  - OBJECTIVES: Factors related to the utilization of dental care by 5- to 11-year
      old children from low-income households were investigated using a comprehensive
      multivariate model that assessed the contribution of structure, history,
      cognition, and expectations. The influence of dentist-patient interactions,
      psychosocial and health beliefs, particularly fear of the dentist, on utilization
      were investigated. METHODS: Children were chosen randomly from public schools,
      and 895 mothers were surveyed and their children were interviewed in the home.
      Utilization was studied during the 1991-1992 school year, including a 6-month
      follow-up period after the interview. RESULTS: The overall utilization rate was
      63.2%, and the rate for nonemergent (preventive) visits was 59.9%. Utilization
      was unrelated to actual oral health status. Race and years the guardian lived in
      the United States were predictive of an episode of care. Preventive medical
      visits and perceived need were strong predictors of a visit to the dentist, as
      were beliefs in the efficacy of dental care. Mothers who were satisfied with
      their own care and oral health and whose children were covered by insurance were
      more likely to utilize children's dental care. In contrast, child dental fear and
      absences from school for family problems were associated with lower rates of
      utilization. CONCLUSIONS: Mutable factors that govern the use of care in this
      population were identified. These findings have implications for the design of
      dental care delivery systems for children and their families.

PMID- 9544596
TI  - SF-36 summary scores: are physical and mental health truly distinct?
AB  - OBJECTIVES: Data from 536 primary care patients initiating antidepressant
      treatment were used to examine the performance of the Medical Outcomes Study SF
      36 Physical Component and Mental Component summary scores. METHODS: The SF-36 was
      administered at baseline and readministered after 1 month and 3 months (n = 482).
      RESULTS: At the baseline assessment, patients reported modest impairment on the
      Physical Function, Role--Physical, Bodily Pain, and General Health Perceptions
      subscales (0.10 to 0.68 standard deviations below national norms), but the
      Physical Component summary (mean = 51) indicated no impairment based on a
      population norm of 50. During 3 months of follow-up evaluation, the Physical
      Function, Role--Physical, Bodily Pain, and General Health Perceptions subscales
      all showed moderate and statistically significant improvement (range from 0.28 to
      0.49 standard deviation units), whereas the Physical Component summary score was
      essentially unchanged (mean = 50 at both 1-month and 3-month assessments). This
      pattern of results is a natural consequence of the assumptions and methods used
      to calculate these summary scores-orthogonal factor rotation and negative scoring
      coefficients. CONCLUSIONS: These findings suggest caution in the interpretation
      of Mental Component Summary and Physical Component Summary scores when the
      condition or treatment of interest has strong effects on scales with negative
      scoring coefficients (Mental Health and Role--Emotional for the Physical
      Component; Physical Function, Role--Physical, and Bodily Pain for the Mental
      Component).

PMID- 9544597
TI  - Psychiatric morbidity and physician visits: lessons from Ontario.
AB  - OBJECTIVES: The authors examine the association between psychiatric morbidity and
      visits to general practitioners and family practitioners in Ontario, Canada.
      METHODS: A nested set of hypotheses were posed to account for different levels of
      use among persons with differing levels of psychiatric morbidity. The sample of
      8,116 is drawn from a comprehensive household survey of physical and mental
      health that included the UM-CIDI standardized diagnostic interview. RESULTS: The
      findings suggest that persons with psychiatric disorders make more visits than
      can be accounted for by sociodemographic factors, medical status, access, or by
      intentional use of the general medical system for mental health treatment.
      CONCLUSIONS: Psychiatric morbidity is associated with higher rates of health
      service use. This effect is strongest among persons with multiple psychiatric
      disorders.

PMID- 9544598
TI  - An economic evaluation of home care for children with newly diagnosed diabetes:
      results from a randomized controlled trial.
AB  - OBJECTIVE: This study was undertaken to determine the health and cost effects of
      using home care to treat newly diagnosed Type I diabetic children rather than
      traditional inpatient hospital care. There had been no well-designed evaluations
      of home care for such children, and very few for children with other health
      conditions. METHODS: Sixty-three children seen at the Montreal Children's
      Hospital were randomly assigned at diagnosis to home care or traditional
      inpatient care. The children in the former group were discharged once their
      metabolic condition stabilized; insulin adjustments and teaching were done in
      their homes by a trained nurse. The children in the latter group remained
      hospitalized for insulin adjustments and teaching. All were followed for 24
      months. The cost effects were estimated using hospital and parental data.
      RESULTS: Social costs were only $48 higher with home care. It had little effect
      on social costs, because the increased costs of health care services with home
      care ($768) were largely offset by parental cost savings ($720). Home care
      improved the children's metabolic outcomes without adversely affecting their
      psychosocial outcomes. CONCLUSIONS: Using home care to reduce hospital stays for
      children with newly diagnosed Type I diabetes improved the children's health
      outcomes without significantly increasing social costs.

PMID- 9544599
TI  - Emergency Department Observation Unit versus hospital inpatient care for a
      chronic asthmatic population: a randomized trial of health status outcome and
      cost.
AB  - OBJECTIVES: This study was designed to determine if an accelerated treatment
      protocol administered to acute asthmatics presenting to a Hospital Emergency
      Department Observation Unit (EDOU) can offset the need for inpatient admissions
      and reduce total cost per episode of care without sacrificing patient quality of
      life. METHODS: The authors used a prospective randomized controlled trial
      comparing postintervention patient quality of life for EDOU care versus standard
      inpatient care as measured by the standardized Medical Outcomes Study (MOS) SF-36
      instrument. Other measures reported include: clinical status as measured by peak
      flow rates, total cost per treatment arm using microcosting techniques, and
      relapse-free survival 8 weeks after treatment. Eligible patients (n = 113) were
      assigned randomly to an EDOU or inpatient care from a consecutive sample of 250
      acute asthmatic patients presenting to an urban hospital emergency department who
      could not resolve their acute asthma exacerbation after 3 hours of emergency
      department therapy. RESULTS: Patients assigned to the EDOU had lower mean costs
      of treatment (EDOU = $1,202 versus Hospital Inpatient = $2,247) and higher
      quality of life outcomes after intervention in five of eight domains measured by
      the MOS SF-36: Physical Functioning, Role Functioning-Emotional, Social
      Functioning, Mental Health, and Vitality. No differences were found in clinical
      outcomes as measured by peak flow rates or postintervention relapse-free
      survival. Univariate comparative findings were re-examined and confirmed through
      multivariable analysis when baseline SF-36 scores and postintervention peak
      expiratory flow rates clinical status were used as covariates. CONCLUSIONS: The
      study showed that the EDOU was a lower cost and more effective treatment
      alternative for a refractory asthmatic population presenting to the Emergency
      Department. Several baseline MOS SF-36 domains proved useful in predicting or
      validating posttreatment clinical status, relapse, and total costs of care.
      Outcome SF-36 domain scores were also useful in identifying patients with the
      most favorable clinical, cost, and relapse rate outcomes at the study endpoint.

PMID- 9544601
TI  - "Appearing twin": undercounting of multiple gestations on early first trimester
      sonograms.
AB  - An important role of first trimester sonography is to determine whether a
      pregnancy is a singleton, twin, or higher order multiple gestation. We assessed
      how frequently sonography at 5.0-5.9 weeks undercounts multiple gestations. We
      identified all pregnancies at our institution since 1988 in which (1) an initial
      sonogram obtained at 5.0-5.9 weeks demonstrated at least a singleton intrauterine
      pregnancy and (2) a subsequent sonogram at 6.0 weeks or beyond demonstrated a
      living multiple gestation. Twenty-four (11%) of 213 dichorionic twin gestations
      were initially undercounted as singletons, as were six (86%) of seven
      monochorionic twin gestations. Among 105 higher order multiples, 17 (16%) were
      undercounted initially. All but one of the undercounted cases were scanned
      transvaginally. Undercounting occurred in both natural and assisted conceptions,
      and it occurred more frequently on sonograms obtained at 5.0-5.4 weeks than at
      5.5-5.9 weeks (P = 0.02, Fisher's exact test). Prognosis for undercounted
      multiple gestations was similar to that of correctly counted ones with respect to
      several measures of pregnancy outcome, including the likelihood that all fetuses
      would be delivered liveborn, gestational age at birth, and birth weight (P >
      0.20, all comparisons). In conclusion, transvaginal sonography at 5.0-5.9 weeks
      frequently undercounts multiple gestations. Initially undercounted multiple
      gestations and those correctly counted have similar pregnancy outcomes.

PMID- 9544600
TI  - Dimensions and correlates of physician work satisfaction in a midwestern city.
AB  - OBJECTIVES: The purpose of this study was to examine the dimensions of physician
      work satisfaction across a variety of medical specialties and practice settings.
      METHODS: A modified version of the Scheckler et al survey instrument was mailed
      to all physicians in Marion County, Indiana. Forty-two percent (777) of the
      eligible physicians responded. Exploratory factor analysis and internal
      consistency measures were used to assess the instrument's validity and
      reliability. Multivariable linear regression was used to predict global and
      summary scale scores. RESULTS: Four dimensions of physician work satisfaction
      were identified: relationships with patients (k = 6, alpha = 0.81), autonomy in
      clinical decision-making (k = 8, alpha = 0.81), office resources (k = 7, alpha =
      0.87), and professional relationships (k = 5, alpha = 0.82). Most (73%) of the
      physicians were satisfied with their overall practice, and the majority were also
      satisfied with their income. Significant differences were observed in the sources
      and magnitude of physician work satisfaction across medical specialty, practice
      setting, and financial arrangement. Physicians in private practice were most
      satisfied with their overall practice and office resources, whereas physicians in
      health maintenance organizations (HMOs) were most satisfied with their autonomy
      in clinical decision-making. Physicians not working in HMOs but having a large
      percentage of patients with capitated reimbursement were not enthusiastic about
      the effect of managed care on their medical practice. Among primary care
      physicians, family practitioners and general internists were generally less
      satisfied, and general pediatricians were generally more satisfied with most
      aspects of their medical practices. CONCLUSIONS: The modified version of the
      Scheckler et al instrument is a reliable and valid measure of physician work
      satisfaction. Increases in the market share of managed care have differentially
      affected the work satisfaction of physicians based on their medical specialty,
      practice setting, and financial arrangements.

PMID- 9544603
TI  - Distention of the fetal duodenum: abnormal finding?
AB  - We investigated whether a fluid-filled duodenum is observed in normal fetuses. In
      part 1 of the study a view in the region of the duodenum was obtained during
      routine obstetric ultrasonography from 123 low-risk patients. All examinations
      demonstrated a collapsed duodenum. No gastrointestinal abnormalities were found
      in these infants. In part 2 of the study, 1163 fetuses (both high-risk and low
      risk) were evaluated with real-time scanning, and duodenal fluid without a
      "double bubble" was seen in one fetus who had a duodenal web. We conclude that a
      nondistended fetal duodenum is the norm. If fetal duodenal dilation is
      visualized, this may allow for earlier detection of duodenal obstructions.

PMID- 9544602
TI  - Gallbladder polyps: prospective study.
AB  - The aim of this study was to describe the natural history of gallbladder polyps.
      Thirty-eight subjects who had been previously identified as having gallbladder
      polyps in an epidemiologic study of gallstone prevalence in 627 diabetic subjects
      and matched controls were followed longitudinally. Follow-up sonograms were
      obtained on 33 and 22 of the 38 subjects at 2 and 5 years, respectively.
      Prevalence for gallbladder polyps in this population was 6.7%, with a marked male
      predominance (odds ratio 2.3). No statistical difference in prevalence was found
      between diabetic subjects and nondiabetic controls. Ninety percent of the polyps
      were less than 10 mm in diameter, with no polyp being larger than 12 mm. During
      the follow-up period no changes suggestive of malignant transformation were
      observed. In conclusion, we found that gallbladder polyps were relatively common
      and that few significant changes occurred over a 5 year period. In asymptomatic
      subjects in whom gallbladder polyps less than 10 mm in diameter are found
      incidentally, the likelihood of malignant transformation is low.

PMID- 9544604
TI  - Appendiceal ultrasonography performed by nonradiologists: does it help in the
      diagnostic process?
AB  - We performed a retrospective study to compare the sensitivity, specificity,
      predictive value, and diagnostic accuracy of appendiceal ultrasonography
      performed by unsupervised technicians during the nighttime hours with studies
      performed during the day by supervised technicians. Fifty-nine percent of the 163
      sonographic examinations were done during the day, and 41% were performed at
      night. The sensitivity during the day (61%) was significantly higher than at
      night (26%), as was the positive predictive value (93% day, 71% night). We
      conclude that ultrasonography is an operator-dependent study. Its sensitivity is
      so diminished when not performed by an experienced radiologist or technician that
      a negative examination is not reliable.

PMID- 9544605
TI  - Fetal cerebral and umbilical artery blood flow changes during pregnancy
      complicated by malaria.
AB  - The objectives of our study were to quantify the fetal cerebral artery and
      umbilical artery blood flow changes daily during a malaria crisis in a pregnant
      patient and evaluate the sensitivity and the specificity of Doppler indices for
      the prediction of acute fetal distress at the end of the pregnancy. The study,
      designed as a prospective and observational one, was carried out in the obstetric
      department of a government hospital in French Guiana, on 23 women with
      pregnancies complicated by malaria (age range, 23 +/- 5 years; primiparas, 30%);
      crisis date: 30.8 +/- 2.5 weeks of gestation; start of treatment: 3.7 +/- 1.3
      days after crisis started). The main measures of outcome consisted of daily
      determinations of fetal Doppler indices during the crisis, evidence of fetal
      distress (fetal heart rate decelerations) during labor, Apgar scores after birth,
      gestational age at birth, mode of delivery, and birth weight. During the crisis
      umbilical artery resistance index increased by 5 to 20% (P < 0.05), cerebral
      artery resistance index decreased by 5 to 20% (P < 0.05), and CURR decreased by
      10 to 35% (P < 0.01), indicating flow redistribution toward the brain. No
      relationship was found between the CURR value and the following data: parasitemia
      grade, parity, gestational age of the crisis, date and mode of delivery, and
      fetal weight. A change in the hypoxia index (% change in CURR during the crisis x
      number of days of crisis) greater than 150 was associated with abnormal fetal
      heart rate in 75% of the cases, and a hypoxia index lower than 150 was associated
      with normal fetal heart rate in 90% of the cases (sensitivity, 89%; specificity,
      77%). Lastly, the combination (hypoxia index > 150 and CURR < 1) was associated
      with abnormal fetal heart rate in 80% of the cases, and one or two of these
      normal parameters were associated with normal fetal heart rate in 84.6% of the
      cases (sensitivity, 80%; specificity, 84%). The CURR and the hypoxia index during
      the malaria crisis can be used to predict acute fetal distress at delivery.

PMID- 9544606
TI  - Sonographic analysis of gallbladder findings in Salmonella enteric fever.
AB  - The purpose of this study was to analyze gallbladder sonographic findings
      associated with Salmonella typhi enteric fever. Sixty-two patients with culture
      positive Salmonella enteric fever were analyzed with serial sonography. The
      following gallbladder sonographic findings were noted: globular gallbladder
      distention (33 of 62 patients, 530%), positive sonographic Murphy sign (25
      patients, 40%), pericholecystic edema or fluid (25 patients, 40%), gallbladder
      wall thickening > 4 mm (21 patients, 34%), low-level nonshadowing intraluminal
      echoes or sludge (nine patients, 15%), intramural linear sonolucency or striation
      (eight patients, 13%), and mucosal irregularity or sloughed membrane (four
      patients, 6%). Using the sonographic findings a gallbladder score was devised to
      assess the severity of gallbladder changes, and the score was correlated with the
      following clinical parameters--duration of fever, multidrug resistance, and
      clinical outcome. An abnormal gallbladder score was noted in 37 patients (60%),
      and multidrug resistance was noted in 35 of these patients (95%). The gallbladder
      scores showed a strong positive correlation with the duration of fever and the
      frequency of multidrug resistance. All 62 patients were treated with intensive
      antibiotic therapy without any deaths.

PMID- 9544607
TI  - Three-dimensional gray scale ultrasonographic imaging of the celiac axis:
      preliminary report.
AB  - The vessels of the celiac axis were evaluated in 16 healthy volunteers with three
      dimensional gray scale ultrasonography. Sonographic volume data sets were
      obtained from both sagittal and transverse planes. The visualization of specific
      branches of the celiac artery (hepatic, splenic, left gastric, gastroduodenal,
      left hepatic, right hepatic, right gastric) was evaluated, and each vessel was
      placed in one of four categories on the basis of the appearance of the specific
      vessel and image clarity (not seen, poorly seen, adequately seen, well seen).
      Each vessel was evaluated on an initial two-dimensional scan and on a second scan
      using the entire volume to optimize and follow the designated vessel using
      rotating, referencing, and scrolling display capabilities. The ability to
      manipulate an entire volume improved visualization of the selected vessels as
      noted by an improved score. The proportion of vessels in the "not seen" and
      "poorly seen" categories decreased from the initial scan (62.5%) to the scan
      utilizing the entire volume (36%). Alternatively, the percentage of vessels in
      the "adequately seen" to "well seen" categories improved from 37.50% on the
      initial examination to 64% on the scans using the entire volume to depict
      vascular anatomy. The optimal plane to image each vessel depended on the course
      of a specific vessel. For optimal imaging of all the selected vessels, both
      sagittal and transverse volume acquisitions and both sagittal and transverse
      planes were needed. Three-dimensional imaging provided a new imaging plane
      (coronal) that was useful in following and identifying vessels, especially those
      vessels coursing in a right to left direction. Vascular variants were identified
      by this technique in two of 16 subjects. Vascular imaging was improved with three
      dimensional ultrasonography, and this imaging method may provide additional
      assistance in decision making when evaluating abdominal vessels.

PMID- 9544608
TI  - Ultrasonographic-surgical correlation of ankle tendon tears.
AB  - This study evaluates the accuracy of ultrasonography in detecting ankle tendon
      tears of the peroneal, posterior tibial, and flexor digitorum longus tendons
      based on operative findings and clinical follow-up. A prospective study was
      performed in 33 patients with clinically suspected tendon injury. Sixty-eight
      tendons were evaluated sonographically. The diagnosis of an intrasubstance tear
      was made when disruption of uniform tendon architecture by hypoechoic linear or
      globular clefts was observed. Criteria used to diagnose complete tendon rupture
      included discontinuity or gap within the tendon or complete nonvisualization of
      the tendon. Treatment decisions were based on a combination of clinical
      parameters and imaging studies. Twenty-six patients had the presence or absence
      of tear confirmed at surgery. Five patients had a final diagnosis based on
      clinical findings, and two were lost to follow-up. Of the 68 tendons evaluated
      sonographically, 54 were directly inspected at surgery; 20 were found to be torn
      and 34 were intact. Ultrasonography was able to identify all tears correctly with
      an accuracy of 93%, a sensitivity of 100%, and a specificity of 88%. The positive
      and negative predictive values were 83% and 100%, respectively. The combined
      accuracy, sensitivity, and specificity of ultrasonography in detecting tendon
      tears in all patients evaluated both surgically and by clinical follow-up were
      94%, 100%, and 90%, respectively.

PMID- 9544609
TI  - Iliotibial band friction syndrome: sonographic findings.

PMID- 9544610
TI  - Congenital transverse vaginal septum: vaginal hydrosonographic diagnosis.

PMID- 9544611
TI  - Prenatal ultrasonographic diagnosis of a simple umbilical hernia.

PMID- 9544612
TI  - A photodetoxification mechanism of the cyanobacterial hepatotoxin microcystin-LR
      by ultraviolet irradiation.
AB  - When microcystin-LR was exposed to UV, three major nontoxic compounds were
      formed. These compounds were identified as [4(E),6(Z)-Adda5]- and [4(Z),6(E)
      Adda5]microcystin-LR, which are geometrical isomers of the Adda [3-amino-9
      methoxy-2,6,8-trimethyl-10-phenyl-4(E),6(E)-decadienoic acid] moiety of
      microcystin-LR, and a novel compound, tricyclo-Adda
      [(2S,3S,1'R,3'S,4'S,5'R,6'R,7'R)-3-amino-5-(4',6'-dimethyl-3'-methoxy
      tricyclo[5.4.0.0(1',5')]undeca-8',10'-dien-6'-yl)-2-methy l-4(E)-pentenoic acid]
      containing microcystin-LR ([tricyclo-Adda5]microcystin-LR), which was formed by
      [2 + 2] addition between the benzene ring and the double bond at position 6-7 of
      the Adda moiety of the microcystin. The geometrical isomers were formed
      reversibly, and their equilibrium constants were almost the same. [Tricyclo
      Adda5]microcystin-LR was also formed reversibly and was decomposed under UV
      light. These results suggest that the breakdown of microcystin-LR by UV
      irradiation proceeds via [tricyclo-Adda5]microcystin-LR.

PMID- 9544613
TI  - Immunochemical detection and identification of protein adducts of diclofenac in
      the small intestine of rats: possible role in allergic reactions.
AB  - Idiosyncratic adverse drug reactions are unpredictable, target multiple organ
      systems, and often become life-threatening events. Although the causes of
      idiosyncratic adverse drug reactions are not known in most cases, evidence
      suggests that they may be mediated through immunological mechanisms. It is
      generally thought that for a drug to lead to an immune response, it must first
      become covalently bound to a carrier protein. Since most drugs are unreactive, it
      is usually a reactive metabolite that is expected to form covalent adducts.
      However, it is not clear why more people do not develop immune reactions against
      drug-protein adducts. One possible explanation is that orally administered drugs
      may lead to oral tolerance in most individuals through mechanisms similar to that
      found with orally administered antigens. However, very little is known regarding
      the interaction of drugs with gut-associated lymphoid tissue of the small
      intestine, where oral tolerance can develop. As an initial step to test this
      hypothesis, we have investigated whether diclofenac, a commonly used nonsteroidal
      antiinflammatory drug, can lead to protein adducts in rat small intestine.
      Diclofenac was administered to rats by gastric gavage. Immunoblot analysis of
      small intestine homogenates and isolated enterocyte subcellular fractions with
      drug-specific antiserum revealed 142-, 130-, 110-, and 55-kDa protein adducts of
      diclofenac. The 142- and 130-kDa adducts of diclofenac were identified as
      aminopeptidase N (CD13) and sucrase-isomaltase, respectively, by amino acid
      sequence analyses and by their reactions with protein-specific antibodies. The
      adducts were localized by immunohistochemistry and found primarily in the mid
      villus and villus-tip enterocytes and also in the dome overlying Peyer's patches.
      Similar adducts were detected immunochemically in villus-tip enterocytes of
      animals treated with halothane or acetaminophen. These results show that
      intestinal protein adducts of drugs can be formed in gut-associated lymphoid
      tissue where they may lead to the down-regulation of drug-induced allergic
      reactions in many individuals.

PMID- 9544614
TI  - Drug-photosensitized protein modification: identification of the reactive sites
      and elucidation of the reaction mechanisms with tiaprofenic acid/albumin as model
      system.
AB  - Certain drugs can photosensitive the formation of protein modifications, which
      are thought to be responsible for the occurrence of photoallergy. In the present
      work, the UV irradiation of serum albumin in the presence of tiaprofenic acid has
      been studied as a model system for drug-photosensitized protein modifications.
      The photolysates evidenced that His, Tyr, and Trp are the reactive sites of the
      protein. The experimental results strongly suggest that formal hydrogen
      abstraction from the OH or NH groups of Tyr or Trp by the excited drug is the key
      photochemical process. Competition between cage escape and in cage recombination
      of the resulting radical pairs governs the final outcome: protein photo-cross
      linking versus drug-protein adduct formation. These findings are highly relevant
      to understand the process of photohapten formation, the first event in the onset
      of photoallergy.

PMID- 9544615
TI  - Identification of a rat liver microsomal esterase as a target protein for
      bromobenzene metabolites.
AB  - The hepatotoxicity of bromobenzene and many other simple organic molecules has
      been associated with their biotransformation to chemically reactive metabolites
      and the subsequent covalent binding of those metabolites to cellular
      macromolecules. To identify proteins targeted by bromobenzene metabolites, we
      incubated [14C]bromobenzene in vitro with liver microsomes from phenobarbital
      induced rats under conditions which typically led to covalent binding of 2-4 nmol
      equiv of bromobenzene/mg of protein. Microsomal proteins were solubilized with
      detergent, separated by chromatography and electrophoresis, and analyzed for 14C
      by phosphorimaging of stained blots. Much of the radioactivity was associated
      with several bands of proteins of ca. 50-60 kDa, plus another prominent band
      around 70 kDa, but labeling density appeared to vary considerably overall. A
      major radiolabeled protein was purified by preparative electrophoresis and
      submitted to automated Edman microsequencing. Its N-terminal sequence was found
      to correspond to that of a known rat liver microsomal carboxylesterase (E.C.
      3.1.1.1) previously identified as a target for reactive metabolites of halothane.
      The extent to which covalent modification of this protein by reactive metabolites
      contributes to the production of hepatotoxic effects remains to be determined.

PMID- 9544616
TI  - Immunochemical detection of hepatic cocaine-protein adducts in mice.
AB  - Cocaine is capable of producing hepatic necrosis in laboratory animals and
      humans. Studies in mice indicate that N-oxidative metabolism of cocaine is
      required for hepatotoxicity and have suggested that toxicity may result from the
      adduction of proteins by cocaine-reactive metabolites. To aid in identifying
      protein targets for cocaine-reactive metabolites, an antibody was raised in
      rabbits immunized with cocaine linked via the tropane nitrogen to a carrier
      protein (bovine serum albumin). Hepatic proteins from cocaine-treated mice (ICR
      males, 50 mg of cocaine/kg of body weight, ip) and saline-treated controls were
      prepared from whole liver homogenate or following subcellular fractionation, and
      Western blot analyses of hepatic proteins using this antibody were conducted
      following one- and two-dimensional SDS-PAGE. Analysis of liver homogenate from
      cocaine-treated mice revealed major protein targets with approximate molecular
      masses of 20 kDa (pI = 6.0), 44 kDa (two proteins with pI's of 5.0 and 7.0), 52
      54 kDa (pI = 4.5), and 64 kDa (pI = 5.5). These specific protein targets were
      shown to be localized in the mitochondria and microsomes. Several minor bands of
      immunoreactivity were also seen in mice treated with cocaine, but not in saline
      treated controls. Pretreatment of mice with the P450 inhibitor SKF 525A
      diminished or eliminated the formation of these cocaine-protein adducts. Liver
      sections from cocaine-treated mice immunostained using the antibody indicated the
      presence of cocaine-adducted proteins in the centrilobular and midzonal regions
      of the lobule, corresponding to areas of hepatocyte swelling and necrosis. This
      study indicates that reactive metabolites from cocaine bind to discrete proteins
      in specific regions of the liver, consistent with a role for protein adduction in
      cocaine hepatotoxicity.

PMID- 9544617
TI  - Synthesis of enzymatically noncleavable carbocyclic nucleosides for DNA-N
      glycosylase studies.
AB  - Carbocyclic nucleosides have been of great interest as antiviral agents and in
      studies in the area of antisense technology. The recent finding that the
      replacement of a single 2'-deoxynucleoside in DNA by a carba analogue does not
      alter the Watson-Crick base pairing, yet at the same time provides a chemically
      and enzymatically stable "glycosidic" linkage, led us to examine this class of
      compound as enzyme inhibitors of the DNA-repair enzymes involved in oxidative
      damage. We now report the synthesis and incorporation into oligomeric DNA via
      suitable derivatives, the carbanucleosides 8-oxo-7,8-dihydro-2'
      deoxycarbainosine, 8-oxo-7,8-dihydro-2'-deoxycarbaguanosine, and 2'
      deoxyaristeromycin. Aristeromycin (1) was deoxygenated at the 2'-position as
      follows. Treatment of 1 with TPDSCl2 gave the 3',5'-protected derivative 3 (76%)
      which on phenylthiocarbonylation at the 2'-position gave 4 in 51% yield. The
      latter compound on reduction with Bu3SnH led to the 2'-deoxy derivative 5 (90%).
      Benzoylation followed by deprotection with TBAF in THF then gave the desired
      intermediate (6) in 65% yield. N2-Isobutyryl-8-oxo-7,8-dihydro-2'
      deoxycarbaguanosine (16) was synthesized from 3-chloro-2'-deoxycarbainosine (9).
      Treatment of 9, either with hydrazine followed by catalytic reduction of the 2
      hydrazino derivative or with 1-(2-nitrophenyl)ethylamine followed by photolysis
      of the resulting 2-substituted derivative, in both instances gave the desired 2'
      deoxycarbaguanosine (12) in approximately 50% overall yield in each case.
      Bromination of 12 gave 13 (90%) which, when treated with BnONa in DMSO at 65
      degrees C, led to the 8-benzyloxy derivative 14 (46%). Isobutyrylation of 14
      followed by catalytic reduction then afforded 16. 8-Oxo-7,8-dihydro-2'
      deoxycarbainosine (23) was prepared in four steps. Bromination of 2'
      deoxyaristeromycin (19) at the 8-position gave 20 (> 95%) which was converted to
      the 8-benzyloxy derivative 21 (61%) using BnONa/DMSO at 80 degrees C. Reductive
      debenzylation of 21 then led to 8-oxo-7,8-dihydro-2'-deoxyaristeromycin
      (approximately 100%) which, when treated with adenosine deaminase, provided the
      desired carbainosine derivative 23 in quantitative yield. Compounds 6, 16, and 23
      were converted to their respective 5'-O-DMT, 3'-O-[(2-cyanoethoxy)-(N,N
      diisopropylamino)phosphine] derivatives (8, 18, and 25) in excellent overall
      yields. The latter were then used to synthesize a series of DNA oligomers by
      automated procedures.

PMID- 9544618
TI  - A mitomycin-N6-deoxyadenosine adduct isolated from DNA.
AB  - A minor N6-deoxyadenosine adduct of mitomycin C (MC) was isolated from synthetic
      oligonucleotides and calf thymus DNA, representing the first adduct of MC and a
      DNA base other than guanine. The structure of the adduct (8) was elucidated using
      submilligram quantities of total available material. UV difference spectroscopy,
      circular dichroism, and electrospray mass spectroscopy as well as chemical
      transformations were utilized in deriving the structure of 8. A series of
      synthetic oligonucleotides was designed to probe the specificities of the
      alkylation of adenine by MC. The nature and frequency of the oligonucleotide-MC
      adducts formed under conditions of reductive activation of MC were determined by
      their enzymatic digestion to the nucleoside level followed by quantitative
      analysis of the products by HPLC. The analyses indicated the following: (i) (A)n
      sequence is favored over (AT)n for adduct formation; (ii) the alkylation favors
      the duplex structure; (iii) at adenine sites only monofunctional alkylation
      occurs; (iv) the adenine-to-alkylation frequency in the model oligonucleotides
      was 0.3-0.6 relative to guanine alkylation at the 5'-ApG sequence but only 0.02
      0.1 relative to guanine alkylation at 5'-CpG. The 5'-phosphodiester linkage of
      the MC-adenine adduct is resistant to snake venom diesterase. The overall ratio
      of adenine to guanine alkylation in calf thymus DNA was 0.03, indicating that 8
      is a minor MC-DNA adduct relative to MC-DNA adducts at guanine residues in the
      present experimental residues in the present experimental system. However, the
      HPLC elution time of 8 coincides with that of a major, unknown MC adduct detected
      previously in mouse mammary tumor cells treated with radiolabeled MC [Bizanek,
      R., Chowdary, D., Arai, H., Kasai, M., Hughes, C. S., Sartorelli, A. C.,
      Rockwell, S., and Tomasz, M. (1993) Cancer Res. 53, 5127-5134]. Thus, 8 may be
      identical or closely related to this major adduct formed in vivo. This
      possibility can now be tested by further comparison.

PMID- 9544619
TI  - Effect of cadmium exposure on background and anti-5 methylchrysene-1,2
      dihydrodiol 3,4-epoxide-induced mutagenesis in the supF gene of pS189 in human
      Ad293 cells.
AB  - Cadmium is a toxic environmental contaminant that is carcinogenic in humans and
      rodents. Although cadmium has proven to be mutagenic in a variety of assay
      systems, exactly how cadmium achieves gentoxicity is poorly understood. To define
      the mechanism(s) underlying the mutagenicity and comutagenicity of cadmium, human
      Ad293 cells were exposed to subtoxic doses of the metal and transfected with
      untreated or anti-5-methylchrysene-3,4-dihydrodiol 1,2-epoxide (5-MCDE)-treated
      pS189 shuttle vector. Alterations in the frequency, types, and distribution of
      mutations were subsequently assessed in the supF gene of pS189 that was
      replicated in Ad293 cells and screened in indicator bacteria. Doses of 0.5 and 1
      microM CdCl2 increased the mutation frequency of untreated pS189 by approximately
      4- and 8-fold, respectively, with no apparent effect on the types of mutations
      generated. In contrast, host-cell exposure to cadmium had little or no effect on
      the frequency, types, or distribution of mutations generated with 5-MCDE-treated
      pS189. These results indicate that cadmium increases mutagenesis of untreated
      pS189 by affecting a process that is not involved in mutagenesis of the 5-MCDE
      treated vector. Although it is not clear exactly how host-cell exposure to
      cadmium increases background mutagenesis, presumably, the mutagenic effect does
      not involve cadmium interaction with the cellular machinery used to replicate
      past bulky DNA lesions.

PMID- 9544620
TI  - Metabolism of the food-borne mutagen 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline in humans.
AB  - The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was
      investigated in five human volunteers given a dietary equivalent of 14C-labeled
      MeIQx. The amount of the dose excreted in urine ranged from 20.2% to 58.6%, with
      unmetabolized MeIQx accounting for 0.7-2.8% of the dose. Five principal
      metabolites were detected in urine, and four of the derivatives were
      characterized by on-line UV spectroscopy and by HPLC-MS following immunoaffinity
      chromatography. Two metabolites were identified as the phase II conjugates N2
      (3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl)sulfamic acid (MeIQx-N2-SO3(-)) and N2
      (beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline (MeIQx-N2
      Gl). Two other metabolites were the cytochrome P450-mediated (P450) oxidation
      products 2-amino-8-(hydroxymethyl)-3-methylimidazo[4,5-f]quinoxaline (8-CH2OH
      MeIQx), and N2-(beta-1-glucosiduronyl)-N-hydroxy-2-amino-3,8-dimethylimidaz o[4,5
      f]quinoxaline (NOH-MeIQx-N2-Gl). The latter product is a conjugate of the
      genotoxic metabolite 2-(hydroxyamino)-3,8-dimethylimidazo-[4,5-f]quinoxaline
      (NHOH-MeIQx). A large interindividual variation was observed in the metabolism
      and disposition of MeIQx; these four metabolites and unchanged MeIQx combined
      accounted for 6.3-26.7% of the total dose. The remaining principal metabolite
      found in all subjects accounted for 7.6-28% of the dose. It has not been
      previously identified in rodents or nonhuman primates, and its structure remains
      unknown. P450-mediated ring oxidation of MeIQx at the C-5 position, a major
      pathway of detoxication in rodents, was not detected in humans. Both 8-CH2OH
      MeIQx formation and NHOH-MeIQx formation are catalyzed by P450 1A2 and may be
      useful biomarkers of P450 1A2 activity in humans. The levels of NHOH-MeIQx-N2-Gl
      found in human urine ranged from 1.4% to 10.0% of the dose, which is
      significantly higher than that formed in rodents and nonhuman primates undergoing
      cancer bioassays. Thus, bioactivation of MeIQx by P450-mediated N-oxidation is
      extensive in humans.

PMID- 9544621
TI  - Reaction of the potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy
      2(5H)-furanone (MX) with 2'-deoxyadenosine and calf thymus DNA: identification of
      fluorescent propenoformyl derivatives.
AB  - The potent bacterial mutagen and drinking water disinfection byproduct 3-chloro-4
      (dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was reacted with 2'-deoxyadenosine
      and calf thymus DNA in aqueous solutions at neutral conditions. HPLC analyses of
      the 2'-deoxyadenosine reaction mixtures showed that two previously unidentified
      products were formed. The products were isolated by preparative C18
      chromatography, and their structures were characterized by UV absorbance,
      fluorescence emission, 1H and 13C NMR spectroscopy, and mass spectrometry. It was
      concluded that in both products a propeno bridge had been incorporated between N
      1 and N6 of the adenine unit. In one of the products, the propeno bridge carried
      a formyl group [3-(2'-deoxy-beta-D-ribofuranosyl)-7H-8-formyl[2,1
      i]pyrimidopurine++ + (pfA-dR)], and in the other the substituents consisted of a
      formyl group and a chlorine atom [3-(2'-deoxy-beta-D-ribofuranosyl)-7H-8-formyl-9
      chloro[2,1-i]pyrimid opurine (Cl-pfA-dR)]. These novel adducts exhibited
      fluorescence in the visible region with emission maxima around 460 nm. The yields
      of the products in reactions performed at pH 7.4 and 37 degrees C were about 0.03
      mol %. In reaction of MX with calf thymus DNA, the adduct pfA-dR was formed and
      its yield was about 0.6 adduct/10(5) nucleotides.

PMID- 9544622
TI  - Structural characterization of contaminants found in commercial preparations of
      melatonin: similarities to case-related compounds from L-tryptophan associated
      with eosinophilia-myalgia syndrome.
AB  - On-line HPLC/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) in
      conjunction with NMR has been successfully employed to identify and structurally
      characterize seven contaminants found in three different commercial preparations
      of melatonin. Six of these contaminants were identified as analogues of
      impurities found in contaminated L-tryptophan (an over-the-counter dietary
      supplement) associated with the eosinophilia-myalgia syndrome (EMS) epidemic that
      occurred in the United States during 1989. In particular, our studies identified
      two compounds with MH+ = 249 to be hydroxymelatonin isomers. Four other compounds
      with MH+ = 477 were identified as melatonin-formaldehyde condensation products.
      These compounds are structural analogues of L-tryptophan contaminants, namely,
      'peak C' and 'peak E' that were previously implicated as etiological agents
      causing EMS. It has been reported that melatonin consumption has resulted in
      eosinophilia in some humans taking high doses of this supplement. Although there
      has not been a major outbreak of EMS-like symptoms from consumption of melatonin,
      this study clearly suggests that tighter control and regulation of nutritional
      supplements sold and used as drugs is necessary.

PMID- 9544623
TI  - Glaucoma "valves"--truth versus myth.

PMID- 9544624
TI  - Is advancing wave-like epitheliopathy distinct from whorled microcystic
      dystrophy?

PMID- 9544625
TI  - Decreasing blindness in developing countries.

PMID- 9544626
TI  - Alternative treatment in retinoblastoma.

PMID- 9544627
TI  - Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age
      effect on radiation-related risk.
AB  - OBJECTIVE: This study aimed to investigate the relationship in bilateral
      retinoblastoma survivors between the incidence of second tumors and the age when
      external beam radiation (EBR) was used. DESIGN: A retrospective analysis of
      patients diagnosed with retinoblastoma was performed by examining records for
      background information and treatment information as well as reviewing
      documentation of patients with second nonocular tumors. Two telephone interviews
      were conducted for follow-up as well as inquiries directed to tumor registries
      and state databases. PARTICIPANTS: The original study included 1729 patients
      treated in New York and Boston; the current study includes only the 1506 patients
      treated in New York. Of those, 816 patients were diagnosed with bilateral
      retinoblastoma, had sufficient treatment data to be useful, and survived at least
      1 year from diagnosis. MAIN OUTCOME MEASURES: The subjects were observed for
      evidence of the development of second nonocular tumors. RESULTS: There was a
      significant decrease in tumor-free survival among patients treated with EBR
      before the age of 12 months, but no significant difference between the group
      treated with EBR after the age of 12 months and the group not treated with EBR.
      For tumors in the field of radiation, patients treated with early EBR showed a
      significant decrease in tumor-free survival when compared to patients treated
      with late EBR, with no significant difference between late radiation and no
      radiation. There were no significant differences between groups for tumors out of
      the field of radiation. Significant differences attributable to the use of EBR
      were found only for tumors of the skull and face bones and for tumors of the soft
      tissue of the head. CONCLUSIONS: The long-term effect of radiation treatment on
      survivors of bilateral retinoblastoma is to increase the incidence and affect the
      distribution of second tumors. However, no increased risk is observed for tumors
      out of the field of radiation among patients who underwent radiation, and the
      risk for tumors in the field of radiation is heavily dependent on the age at
      which EBR is given and may be acceptably small to the patient after the age of 12
      months.

PMID- 9544628
TI  - Transpupillary thermotherapy for choroidal melanoma: tumor control and visual
      results in 100 consecutive cases.
AB  - OBJECTIVE: The authors evaluated the results of primary transpupillary
      thermotherapy for choroidal melanoma in 100 cases. DESIGN: Prospective
      nonrandomized analysis of treatment method. PARTICIPANTS: One hundred patients
      with choroidal melanoma were studied. MAIN OUTCOME MEASURES: Tumor response,
      ocular side effects, and visual results. RESULTS: Of 100 consecutive patients
      with choroidal melanoma treated with transpupillary thermotherapy, the mean tumor
      basal diameter was 7.1 mm and tumor thickness was 2.8 mm. The tumor margin
      touched the optic disc in 34 eyes (34%) and was beneath the fovea in 42 eyes
      (42%). Documented growth was present in 64 eyes (64%), and known clinical risks
      for growth were present in all of the remaining 36 eyes (36%), with an average of
      4 of 5 statistical risk factors for growth per tumor. After a mean of three
      treatment sessions and 14 months of follow-up, the mean tumor thickness was
      reduced to 1.4 mm. Treatment was successful in 94 eyes (94%) and failed in 6 eyes
      (6%). Three patients with amelanotic tumors showed no initial response to
      thermotherapy, but subsequent intravenous indocyanine green administration during
      thermotherapy resulted in improved heat absorption and tumor regression to a flat
      scar. The six eyes classified as treatment failures included four eyes with
      tumors that showed partial or no response to thermotherapy, thus requiring plaque
      radiotherapy or enucleation, and two eyes with recurrence, subsequently
      controlled with additional thermotherapy. After treatment, the visual acuity was
      the same (within 1 line) or better than the pretreatment visual acuity in 58 eyes
      (58%) and worse in 42 eyes (42%). The main reasons for poorer vision included
      treatment through the foveola for subfoveal tumor (25 eyes), retinal traction (10
      eyes), retinal vascular obstruction (5 eyes), optic disc edema (1 eye), and
      unrelated ocular ischemia (1 eye). Temporal location (versus nasal and superior,
      P = 0.02) and greater distance from the optic disc (P = 0.04) were risks for
      retinal traction. CONCLUSIONS: Transpupillary thermotherapy may be an effective
      treatment for small posterior choroidal melanoma, especially those near the optic
      disc and fovea. Despite satisfactory local tumor control, ocular side effects can
      result in decreased vision. Longer follow-up will be necessary to assess the
      impact of thermotherapy on ultimate local tumor control and metastatic disease.

PMID- 9544629
TI  - The multidisciplinary management of psammomatoid ossifying fibroma of the orbit.
AB  - OBJECTIVE: To discuss the multidisciplinary management of psammomatoid ossifying
      fibroma (POF) of the orbit and to clarify the clinicopathologic terminology.
      DESIGN: The authors present a cohort of cases of POF involving the frontal and
      ethmoid sinuses and the orbit and discuss the nomenclature and literature.
      PARTICIPANTS: Three patients with POF and their treatment are discussed.
      INTERVENTION: Patients were worked up and treated by a multidisciplinary team
      using imaging studies and histopathologic analysis. Reconstruction, if necessary,
      was carried out at the time of excision or in a second-stage procedure. MAIN
      OUTCOME MEASURES: In each case, the lesion was completely excised and has not
      recurred. RESULTS: The diagnosis of POF was made in each case, and the patient
      underwent successful resection of the tumor. CONCLUSION: The authors' experience
      suggests that a multidisciplinary approach, including a radiologist, pathologist,
      neurosurgeon, otolaryngologist, craniofacial surgeon, and orbital specialist, may
      be useful in the evaluation and management of these lesions.

PMID- 9544630
TI  - Malignant nonteratoid medulloepithelioma of the ciliary body in an adult.
AB  - BACKGROUND: The authors describe a 62-year-old man with a malignant nonteratoid
      malignant medulloepithelioma of the ciliary body with extension into the anterior
      choroid and posterior chamber. He developed gradual loss of vision in his right
      eye, and a clinical diagnosis of malignant melanoma of the ciliary body and
      choroid was made. RESULTS: Histopathologic examination of the enucleated eye
      showed a malignant nonteratoid medulloepithelioma of the ciliary body with
      extension into the anterior choroid and posterior chamber. CONCLUSION: This
      report provides clinicopathologic evidence that intraocular medulloepithelioma
      can occur rarely in an adult. The lesion clinically may mimic a malignant
      melanoma. The authors also summarize five previously reported cases of this
      unusual lesion.

PMID- 9544632
TI  - Results of laser in situ keratomileusis in different degrees of myopia.
AB  - PURPOSE: This study aimed to analyze the results of laser in situ keratomileusis
      (LASIK) in different degrees of myopia. MATERIAL AND METHODS: Three hundred
      consecutive eyes were divided into 4 groups according to their degree of
      preoperative myopia. Group I was between -3 and -6 diopters (D) (28 eyes), low
      myopia. Group II was between -6.25 and -10 D (138 eyes), moderate myopia. Group
      III was between -10.25 and -15 D (91 eyes), high myopia. Group IV was between 
      15.25 and -25.50 D (43 eyes), extremely high myopia. Patients were observed for 6
      to 25 months. RESULTS: For group I, the preoperative spherical equivalent was 
      5.12 D +/- 0.81 standard deviation (SD), corrected visual acuity was 0.88 +/-
      0.14 (SD), and keratometry was 44.09 D +/- 1.65 (SD). At the last check-up, the
      spherical equivalent was -0.42 D +/- 0.98 (SD), corrected visual acuity was 0.89
      +/- 0.15 (SD), keratometry was 39.11 D +/- 1.61 (SD). For group II, preoperative
      spherical equivalent was -8.33 D +/- 1.24 (SD), corrected visual acuity was 0.72
      +/- 0.22 (SD), keratometry was 44.34 D +/- 1.64 (SD). At last check-up, the
      spherical equivalent was -0.19 D +/- 1.22 (SD), corrected visual acuity was 0.76
      +/- 0.17 (SD), keratometry was 37.56 D +/- 1.90 (SD). For group III, the
      preoperative spherical equivalent was -12.37 D +/- 1.49 (SD), corrected visual
      acuity was 0.58 +/- 0.23 (SD), and keratometry was 44.06 D +/- 1.63 (SD). At last
      check-up, spherical equivalent was -0.55 D +/- 1.63 (SD), corrected visual acuity
      was 0.61 +/- 0.18 (SD), and keratometry was 35.88 D +/- 2.18 (SD). For group IV,
      the preoperative spherical equivalent was -19.04 +/- 2.82 (SD), corrected visual
      acuity was 0.37 +/- 0.17 (SD), and keratometry was 44.02 D +/- 1.30 (SD). At last
      check-up, spherical equivalent was -1.49 D +/- 1.54 (SD), corrected visual acuity
      was 0.44 +/- 0.18 (SD), and keratometry was 33.94 D +/- 2.54 (SD). CONCLUSION:
      With some exceptions, LASIK results generally are acceptable and stable.
      Nevertheless, the scatter of some cases shows that there is room for improvement,
      even in the most sophisticated excimer software. The high regression of group I
      proves the need to sample multizone software to determine whether stability is
      improved. Although visual results are better in patients with lower myopia, the
      patients whose eyes had higher ametropia more often showed improvement in their
      visual acuity. This may be because of the greater postoperative size of the image
      on the macula.

PMID- 9544631
TI  - Cutaneous melanoma metastatic to the vitreous cavity.
AB  - OBJECTIVE: The authors report their experience with cutaneous melanoma metastatic
      to the vitreous and elaborate on the features of this entity. DESIGN: The study
      design was a retrospective review. PARTICIPANTS: Three patients with four
      affected eyes from cutaneous melanoma metastatic to the vitreous participated.
      INTERVENTION: All three patients were white men, and their mean age was 58 years.
      The previously excised cutaneous melanomas were all Clark level IV. The mean
      interval from diagnosis of the primary cutaneous melanoma to vitreous metastasis
      was 25 months. Ocular findings included clumps of cells arranged in sheets or
      linear strands on the vitreous framework. The vitreous cells were nonpigmented in
      two cases and pigmented in one case. Neovascular glaucoma was found in all three
      cases. After the diagnosis of vitreous melanoma was made by cytopathologic
      examination, external beam irradiation (5000 cGy) was given in all patients. MAIN
      OUTCOME MEASURES: Local tumor control and survival were measured. RESULTS: At a
      mean follow-up of 14 months from diagnosis of vitreous melanoma, tumor control
      was achieved in only one of the four affected eyes. One eye was enucleated
      because of painful neovascular glaucoma, and the other two eyes had progressive
      vitreous disease. After a mean follow-up of 14 months (from ocular diagnosis),
      all three patients had died. CONCLUSION: Cutaneous melanoma metastatic to the
      vitreous can present with nonpigmented or pigmented cells. Neovascular glaucoma
      frequently is found. External beam radiation therapy often is unsuccessful in
      local tumor control, and systemic prognosis is poor.

PMID- 9544633
TI  - Corneal topography of photorefractive keratectomy versus laser in situ
      keratomileusis. Summit PRK-LASIK Study Group.
AB  - OBJECTIVE: This study aimed to compare qualitative patterns of corneal topography
      early in the postoperative course after excimer laser photorefractive keratectomy
      (PRK) and laser in situ keratomileusis (LASIK) when used for the treatment of
      myopia of 6.0 to 15.0 diopters. DESIGN: The study design was a prospective,
      multicenter, randomized clinical trial. PARTICIPANTS: A total of 64 eyes were
      treated with PRK and 54 eyes were treated with LASIK. INTERVENTION: Using the
      Summit Apex excimer laser, patients received either PRK or LASIK using a single
      pass, multizone excimer laser ablation. Computer-assisted videokeratography was
      performed at designated postoperative examinations. MAIN OUTCOME MEASURES:
      Videokeratography maps at 1 and 3 months after surgery were classified using a
      standard classification scheme. The association of topography patterns to loss of
      spectacle-corrected visual acuity was tested. RESULTS: At 1 month, for the PRK (n
      = 60) and LASIK (n = 51) groups, respectively, 63.3% and 19.6% of eyes fell into
      one of the four optically irregular groups (central island, keyhole,
      semicircular, or irregularly irregular; P < 0.001). At 3 months, for the PRK (n =
      49) and LASIK (n = 39) groups, respectively, 36.7% and 10.3% of eyes fell into
      one of the optically irregular groups (P = 0.004). Comparing the 1- and 3-month
      examination results in the PRK and LASIK groups, respectively, 19 (42%) of 45
      eyes and 11 (31%) of 36 eyes had a change in topography, generally to an
      optically smoother pattern. The irregular groups, taken together, were associated
      with a greater tendency toward loss of spectacle-corrected visual acuity of two
      or more Snellen lines (P = 0.01). There also was greater tendency toward loss of
      spectacle-corrected visual acuity in the PRK group that diminished with time (P <
      0.01 at 1 month, P = 0.05 at 3 months). CONCLUSIONS: After treatment for moderate
      to-high myopia, LASIK topography patterns generally are more regular than are PRK
      patterns. This may be a result either of masking of underlying topography
      perturbations by the lamellar corneal flap, thus mitigating induced topography
      changes, or differences in surface wound healing. This study suggests that more
      rapid return of spectacle-corrected visual acuity found in patients treated with
      LASIK may be a result of more regular topography patterns early in the
      postoperative course.

PMID- 9544634
TI  - Excimer laser photoastigmatic refractive keratectomy: eighteen-month follow-up.
AB  - OBJECTIVE: To study the efficacy of photoastigmatic refractive keratectomy (PARK)
      by the MEL 60 (Aesculap-Meditec, Jana, Germany) scanning excimer laser for the
      treatment of myopic astigmatism, with follow-up of 18 months. PATIENTS AND
      METHODS: One hundred and twenty-eight eyes of 102 patients with different degrees
      of myopic astigmatism were treated by PARK and followed prospectively in an open
      study. Ablations were performed with an MEL 60 excimer laser using an astigmatic
      module. RESULTS: Mean preoperative refractive cylinder improved from a
      preoperative value of -1.8 +/- 0.8 diopters (D; range, -1.0 to -6.0 D) to -0.3 +/
      0.5 D (range, +1.0 to -2.5 D) at 18 months. The mean reduction in cylindrical
      correction alone was 84 +/- 37% in the low astigmatism group (-1.0 to -1.5 D); 91
      +/- 21% in the moderate astigmatism group (-1.75 to -2.5 D); and 75 +/- 25% in
      the high astigmatism group (-2.75 to -6.0 D). One hundred and three eyes (80%) at
      12 months and 100 eyes (85%) at 18 months were within +/-0.5 D of the intended
      astigmatic correction, with more eyes in the low astigmatic group. One hundred
      and nineteen eyes (93%) and 114 eyes (97%) at 12 and 18 months, respectively,
      were within +/-1.0 D of the intended correction. Ninety-two percent to 95.7% of
      the eyes in the different groups had a postoperative axis less than 10 degrees of
      the preoperative and intended axis at 12 and 18 months after PARK. Uncorrected
      visual acuity (UCVA) of 20/40 or better was achieved in nearly 84% of the eyes 12
      and 18 months after PARK. A UCVA of 20/20 was achieved in 49% of eyes 18 months
      after PARK. Ten eyes (8%) underwent reoperation at the end of 12 months.
      CONCLUSIONS: The data indicate that PARK is an effective surgical tool for
      correcting astigmatism, especially astigmatism of 1.0 to -2.5 D, with a success
      rate of approximately 70%.

PMID- 9544635
TI  - Refractive and keratometric results after the triple procedure: experience with
      early and late suture removal.
AB  - OBJECTIVE: The objective of this study was to determine the outcome of early and
      late suture removal after the triple procedure (i.e., penetrating keratoplasty,
      cataract extraction, lens implant). DESIGN AND PARTICIPANTS: The refractive and
      keratometric results of 106 eyes undergoing the triple procedure were reviewed.
      The target postoperative refractive error was -1 diopter (D). RESULTS: Average
      length of follow-up was 40.3 months. Twenty eyes had sutures removed early (<18
      months after surgery), 39 had sutures removed late (> or = 18 months after
      surgery), and 47 had sutures still intact at last follow-up. A best spectacle
      corrected visual acuity of 20/40 or better was achieved in 90% of eyes with
      sutures removed early, 82.1% with sutures removed late, and 70.2% with sutures in
      place. For all eyes, the mean spherical equivalent at last follow-up was -2.50 D,
      with 75% of eyes falling between -4 and +2 D. The mean final refractive error was
      -3.40 +/- 3.53 D for eyes with sutures removed early and -1.79 +/- 3.99 D for
      eyes with sutures removed late. Eyes with sutures remaining had a mean final
      refractive error of -0.33 +/- 2.25 D. There was an overall decrease in refractive
      and keratometric astigmatism after both early and late suture removal with no
      significant difference between groups. However, there was a wide range of change
      with some eyes experiencing a decrease and others an increase in astigmatism.
      Mean postoperative K readings increased significantly for both groups after
      suture removal (final mean K, 47.00 D) but remained stable for eyes with sutures
      in. CONCLUSION: The authors data suggest that the final refractive error and net
      change in refractive and keratometric astigmatism after the triple procedure are
      not dependent on the timing of suture removal.

PMID- 9544636
TI  - Confocal microscopy of cystic disorders of the corneal epithelium.
AB  - OBJECTIVE: This study aimed to describe the morphology of cystic disorders of the
      corneal epithelium by confocal microscopy. DESIGN: The study design was a
      prospective evaluation of confocal microscopic images of patients with cystic
      corneal disorders. PARTICIPANTS: Thirteen patients (19 eyes) were included. The
      corneal disorders included four patients with corneal decompensation (Fuchs'
      dystrophy), five patients with epithelial basement membrane dystrophy (e.g.,
      Cogan's microcystic and map-dot dystrophies), one patient with Meesmann's
      dystrophy, and three patients with recurrent erosion syndrome of unknown
      etiology. Confocal images of diseased corneas were compared with those of ten
      normal control eyes (ten subjects). INTERVENTION: All patients were examined by
      slit-lamp biomicroscopic analysis and confocal microscopic analysis (Tomey,
      Erlangen-Temmenlohe, Germany). Image analysis was used to identify the corneal
      epithelial structures correlated with the corresponding pathology. MAIN OUTCOMES
      MEASURES: Confocal microscopy was used to assess the size, shape, light scatter,
      and reflection of the cysts. RESULTS: Slit-lamp examination results showed
      corneal epithelial cystic lesions in all cases. Confocal microscopy was able to
      identify cystic lesions in 9 (69.2%) of 13 patients. Of the four patients in whom
      lesions could not be found by confocal microscopy, three had recurrent erosion
      syndrome and the other one had epithelial basement membrane dystrophy. The
      confocal images were compatible with the clinical and histologic pictures of the
      disease. Normal control eyes did not show any epithelial lesion, either by
      biomicroscopy or confocal microscopy. CONCLUSIONS: Confocal microscopy provides
      an in vivo evaluation of cystic epithelial corneal lesions. This study shows that
      confocal microscopy is suitable for examining cystic lesions of the corneal
      epithelium. Nevertheless, it is not as sensitive as biomicroscopy in detecting
      cystic lesions in certain corneal conditions.

PMID- 9544637
TI  - Long-term follow-up of patients with atopic keratoconjunctivitis.
AB  - OBJECTIVE: This study aimed to review the presenting features, treatment
      administered to, histopathologic findings, and complications encountered in a
      cohort of patients with atopic keratoconjunctivitis. DESIGN: The study design was
      a retrospective cohort series. PARTICIPANTS: The medical records of 20 patients
      with atopic keratoconjunctivitis and a minimum follow-up of 3 years were
      reviewed. MAIN OUTCOME MEASURES: Conjunctival and corneal complications, visual
      acuity before and after surgery, and histopathologic features on conjunctival
      biopsy were measured. RESULTS: Significant keratopathy developed in 70% of
      patients, corneal neovascularization in 60%, fornix foreshortening in 25%, and
      symblepharon in 20% during the course of their disease. Eleven patients (12 eyes)
      required penetrating keratoplasty (3 for tectonic purposes and 8 for visual
      rehabilitation). Vision improved by four or more lines of Snellen acuity in four
      eyes, improved by two lines in two eyes, remained the same in five eyes, and
      worsened by two lines in one eye after keratoplasty. Cataract surgery was
      performed in seven patients (nine eyes) with vision improving by four or more
      lines in six patients (eight eyes). CONCLUSION: Atopic keratoconjunctivitis is a
      potentially blinding disease that may result in a poor visual outcome as a result
      of corneal complications. Elective surgical intervention may be of benefit and
      can be considered in those patients whose inflammation is well controlled.

PMID- 9544638
TI  - Keratoconjunctivitis sicca associated with achalasia of the cardia,
      adrenocortical insufficiency, and lacrimal gland degeneration:
      Keratoconjunctivitis sicca secondary to lacrimal gland degeneration may parallel
      degenerative changes in esophageal and adrenocortical function.
AB  - OBJECTIVE/DESIGN: This study aimed to examine and describe three siblings with
      alacrima, the eldest of whom had associated achalasia and adrenocortical
      insufficiency. PARTICIPANTS: Three affected siblings and four age-matched control
      subjects participated. INTERVENTION/MAIN OUTCOME MEASURES: The three children
      underwent complete ophthalmologic examinations; computed tomographic scanning of
      brain, orbit, chest, and abdomen; and measurement of serum cortisol. All three
      were subjected to a short synacthen challenge. Lacrimal gland biopsies were
      performed on the two younger subjects, and specimens were studied by light and
      electron microscopy. RESULTS: All three children showed virtually absent tear
      secretion as tested by the Schirmer test. The resulting keratopathy was most
      severe in the oldest child, who developed bilateral corneal melting. The two
      younger children showed interpalpebral corneal staining with rose bengal. All
      three children improved after punctal occlusion. Addison's disease was present in
      the oldest child. Computed tomographic scanning showed absent lacrimal and
      shrunken adrenal glands in association with achalasia of the cardia in the oldest
      child. The lacrimal glands were found to be reduced in size in the next eldest
      child. When evaluated by electron microscopy, the lacrimal gland biopsy specimens
      from the two younger children showed neuronal degeneration associated with
      depletion of secretory granules in the acinar cells. CONCLUSION: In this disease,
      radiologic evidence of reducing lacrimal gland size with increasing age could
      represent a degenerative process. This may be paralleled by other signs and the
      possibility of adrenocortical insufficiency and achalasia of the cardia should be
      investigated in all children presenting with dry eyes. These children appear to
      have a progressive neuronal disease.

PMID- 9544639
TI  - Anterior uveitis and hypotony after intravenous cidofovir for the treatment of
      cytomegalovirus retinitis.
AB  - OBJECTIVE: This study aimed to describe the incidence and risk factors for the
      development of anterior uveitis in patients receiving intravenous cidofovir for
      the treatment of longstanding cytomegalovirus retinitis. DESIGN: The study design
      was a retrospective cohort. PARTICIPANTS: Eighteen patients (30 eyes) receiving
      parenteral cidofovir for the treatment of complicated cytomegalovirus retinitis
      participated. MAIN OUTCOME MEASURES: The clinical response to parenteral
      cidofovir; the occurrence of anterior uveitis, and the management and outcome of
      patients with this complication; and the effect of cidofovir on intraocular
      pressure measurements were measured. RESULTS: There was no progression or relapse
      of retinitis in patients receiving intravenous cidofovir. Eight (44%) of the 18
      patients developed anterior uveitis, which occurred after a median of 4 doses of
      intravenous cidofovir. The median CD4+ cell count at the time of development of
      iritis was 101/mm3. Patients who developed uveitis had a mean increase in serum
      creatinine over baseline measurements (P = 0.05). The use of human
      immunodeficiency virus type-1 (HIV-1) protease inhibitors was not different
      between both groups of patients (P = 1.0). The development of anterior uveitis
      and visually significant hypotony necessitated withdrawal of cidofovir in only
      one patient. CONCLUSIONS: Anterior uveitis was a common complication after
      intravenous cidofovir therapy. Despite the frequency of this complication,
      continued treatment with intravenous cidofovir was possible in the majority of
      patients. Patients with anterior uveitis after intravenous cidofovir may be
      treated successfully with topical corticosteroid therapy and cycloplegic agents.

PMID- 9544640
TI  - Pharmacokinetics of azithromycin in trachoma patients: serum and tear levels.
AB  - OBJECTIVE: To determine the effectiveness of single-dose oral azithromycin in the
      treatment of Chlamydia trachomatis through monitoring of tear and serum levels.
      DESIGN: Nonrandomized, clinical trial. PARTICIPANTS: Fourteen school-age children
      with active trachoma (one failed to complete the study). INTERVENTION: A single
      dose of azithromycin (20 mg/kg) was administered orally to 14 patients, and tear
      and serum levels were determined with high-performance liquid chromatography at
      12, 24, 48, 72, 96, 120, and 144 hours after administration. MAIN OUTCOME
      MEASURES: Azithromycin levels in tears and serum. RESULTS: Peak levels of 1.53
      microg/ml (standard deviation [SD] +/- 0.94) and 0.15 microg/ml (SD +/- 0.04)
      were obtained at 12 hours in both tears and serum, gradually decreasing over 144
      hours. All patients were disease-free by 6 months. CONCLUSIONS: Levels of
      azithromycin in patients with trachoma were found to be within minimum inhibitory
      concentration range for Chlamydia trachomatis (0.03-0.25 microg/ml) throughout
      the monitored period of 6 days.

PMID- 9544641
TI  - Feeder vessel photocoagulation of subfoveal choroidal neovascularization
      secondary to age-related macular degeneration.
AB  - PURPOSE: This study aimed to assess the feasibility of laser photocoagulation of
      feeder vessels of subfoveal choroidal neovascularization (CNV) secondary to age
      related macular degeneration. PATIENTS AND METHODS: Of 170 consecutive patients
      with subfoveal CNV secondary to age-related macular degeneration, feeder vessels
      were detected in 37 patients by means of indocyanine green videoangiography using
      a scanning laser ophthalmoscope. Dye laser photocoagulation was applied to
      extrafoveal feeder vessels, with the fovea spared. RESULTS: Twenty-six (70%) of
      those 37 patients had complete resolution of exudative manifestations. Persistent
      or worsened manifestations were seen in 11 patients (30%) because of recurrent
      CNV or persistent CNV. The visual acuity improved or stabilized in 25 patients
      (68%). Ten patients (27%) had a final visual acuity of 20/40 or better and six
      patients (16%) had a final visual acuity of 20/50 to 20/100. Significant factors
      prognostic of the visual outcome of 20/100 or better were small CNV (2 disc areas
      or smaller, Fisher's exact probability test, P = 0.041), the absence of white,
      fibrous tissue in neovascular membranes (Fisher's exact probability test, P =
      0.003), and the closest distance of laser burns to the center of the foveal
      avascular zone (Fisher's exact probability test, P = 0.049). Preoperative visual
      acuity had a significant positive correlation with final visual acuity
      (Spearman's rank correlation test, P = 0.0076). CONCLUSION: Feeder vessel
      photocoagulation should be considered as a treatment option for subfoveal CNV
      secondary to age-related macular degeneration, because no other treatment method
      has a better visual outcome.

PMID- 9544642
TI  - Laser chorioretinal venous anastomosis for nonischemic central retinal vein
      occlusion.
AB  - OBJECTIVE: This study aimed to test the efficacy and safety of laser
      chorioretinal anastomosis for central retinal vein occlusion (CRVO). DESIGN: The
      study design was a consecutive case series. PARTICIPANTS: Eight eyes of eight
      patients were treated. INTERVENTION: The argon laser was used in the method of
      McAllister and Constable to attempt to form an anastomosis. The patients were
      observed for 1 to 19 months (median, 11 months). MAIN OUTCOME MEASURES: Visual
      acuity, anastomosis success, and complications were measured. RESULTS: Twenty
      attempts to create anastomoses were made with 2 successful anastomoses but not of
      a therapeutic type. Three patients developed rubeosis, retinal neovascularization
      at the laser site, and vitreous hemorrhage. Traction retinal detachment occurred
      twice and neovascular glaucoma occurred once. Secondary panretinal
      photocoagulation, pars plana vitrectomy, and glaucoma seton were required in
      three patients, one patient, and one patient, respectively. Visual acuity
      improved in two patients independent of failed attempts at anastomosis creation
      and did not improve or worsened in six patients, including the two patients with
      the successfully created anastomoses. CONCLUSION: Laser chorioretinal anastomosis
      for nonischemic CRVO has greater risks and less success than the initial report
      suggested. Further refinement of the technique is needed before it is adopted
      extensively. Even when successful, macular pigment epithelial scarring can limit
      vision, implying a relatively short time window for its effective application in
      the face of severe macular edema. Successful laser chorioretinal anastomosis does
      not preclude development of anterior segment neovascularization.

PMID- 9544643
TI  - Digital subtraction indocyanine green angiography of occult choroidal
      neovascularization.
AB  - OBJECTIVE: This study aimed to use a new technique for ocular imaging, digital
      subtraction indocyanine green angiography (DS-ICGA), to evaluate patients with
      occult choroidal neovascularization (CNV). DESIGN: The design was a cross
      sectional study of patients with occult CNV. PARTICIPANTS: A total of 31 eyes of
      31 patients were studied. INTERVENTION: Digital subtraction of sequentially
      acquired indocyanine green angiographic frames was used to image the progression
      of the dye front in eyes with occult CNV. A method of pseudocolor imaging of the
      choroid was developed that allows differentiation and identification of
      underlying choroidal arteries and veins. RESULTS: The DS-ICGA of occult CNV
      showed consistent findings. Occult CNV was imaged with greater detail and in a
      shorter period of time than with conventional indocyanine green angiography. The
      fundus landmarks were retained with DS-ICGA much better than with conventional
      indocyanine green angiography. CONCLUSIONS: The DS-ICGA uses time to dissect the
      choroidal circulation. With DS-ICGA, occult CNV could be imaged more quickly and
      in greater detail than with conventional imaging techniques. The DS-ICGA may
      improve the authors ability to image, and subsequently treat, occult CNV.

PMID- 9544644
TI  - Functional assessment of macular hole surgery by scanning laser ophthalmoscopy.
AB  - OBJECTIVE: This study aimed to evaluate more precisely the benefit of macular
      hole surgery. DESIGN: The design was a prospective study of 40 eyes in 40
      patients examined before and after surgery of full-thickness macular holes with a
      scanning laser ophthalmoscope (SLO). PARTICIPANTS: Forty patients with full
      thickness macular holes participated. Three of the holes were stage 2, 23 were
      stage 3, and 14 were stage 4. INTERVENTION: The SLO examination consisted of
      macular imaging and assessment of macular function using tests produced by an
      acousto-optical modulator. MAIN OUTCOME MEASURES: Preferred retinal locus (PRL)
      was determined, visual acuity was measured, and scotoma was detected by
      microscotometry and by the line test (modified Watzke-Allen test). RESULTS:
      Anatomic success was achieved in 32 of 40 cases as assessed biomicroscopically.
      On SLO examination before surgery, macular holes were seen as a central bright
      round disc outlined by a thin dark edge surrounded by a dark ring and a less dark
      area with ill-defined limits. In all cases, the PRL was located on the upper edge
      of the hole, a scotoma was always detected inside the hole, and the line was seen
      as broken in 26 of 32 cases. After surgery, the hole closed completely in 25 of
      32 eyes; it disappeared from 14 of these 25 eyes and was replaced by a dark or
      clear disc in 11. In the other seven successful cases, its size shrank and its
      edge flattened but remained faintly visible. The hole remained unchanged in eight
      cases. Eccentric PRL became central in 28 of 32 cases. The scotoma disappeared in
      23 of 32 cases. The line was seen as continuous in 24 of 32 cases. Complete
      anatomic and functional successes were achieved in 19 of the 32 cases of macular
      hole closure. CONCLUSION: The SLO examination allows accurate assessment of the
      anatomic and functional results of macular hole surgery. Various degrees of
      functional success were recorded, depending on the test used.

PMID- 9544645
TI  - Comparison of recombinant transforming growth factor-beta-2 and placebo as an
      adjunctive agent for macular hole surgery.
AB  - OBJECTIVE: This study aimed to compare the visual and anatomic results of macular
      hole surgery in eyes treated with recombinant transforming growth factor-beta-2
      (TGF-beta2) or placebo. DESIGN: The design was a prospective, multicenter,
      randomized, double-masked, placebo-controlled clinical study. PARTICIPANTS: One
      hundred thirty eyes with idiopathic macular holes of 1 year or less and a
      refracted Early Treatment Diabetic Retinopathy Study visual acuity of 20/80 or
      worse were treated with 1.1 microg recombinant TGF-beta2 or placebo to the
      macular hole after fluid-gas exchange. INTERVENTION: The effect of recombinant
      TGF-beta2 as an adjunctive agent for macular hole surgery was evaluated. MAIN
      OUTCOME MEASURES: Closure of the macular hole and change in visual acuity at 3
      months were measured. RESULTS: The 3-month visits were completed for 120 eyes.
      The macular hole was closed at 3 months in 35 (61.4%) of 57 eyes treated with
      placebo and 49 (77.8%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.08).
      The mean visual acuity gain was +6.4 letters in eyes receiving placebo and +8.9
      letters in eyes treated with recombinant TGF-beta2 (P = 0.27). Visual acuity
      improved 2 or more lines in 23 (40.4%) of 57 eyes treated with placebo and 30
      (47.6%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.42). Intraocular
      pressure elevation greater than 30 mmHg was more common 2 weeks after surgery in
      eyes treated with recombinant TGF-beta2 (P < 0.001). CONCLUSIONS: Recombinant TGF
      beta2 resulted in a similar proportion of successful closure of macular holes as
      placebo. There was no statistically significant visual acuity benefit with the
      use of recombinant TGF-beta2 for the treatment of macular holes.

PMID- 9544646
TI  - Additional procedures after the initial vitrectomy or tap-biopsy in the
      Endophthalmitis Vitrectomy Study.
AB  - OBJECTIVE: The study aimed to assess the frequency, indications, and outcome of
      additional ocular procedures after initial treatment of vitrectomy (VIT) or tap
      biopsy (TAP) for patients with endophthalmitis after cataract extraction. DESIGN:
      The study design was an analysis of observational data collected as part of a
      multicenter, randomized clinical trial. PARTICIPANTS: Of the 420 patients
      enrolled in the Endophthalmitis Vitrectomy Study, the 148 who had additional
      procedures were compared with the 272 who did not. MAIN OUTCOME MEASURES: The
      types, indications, and number of additional ocular procedures were assessed. A
      masked examiner measured visual acuity 9 to 12 months after study entry. RESULTS:
      Within 1 week of study entry, 8% of VIT eyes and 13% of TAP eyes underwent
      additional procedures, 14% for complications of the initial procedure and 86% for
      worsening ocular inflammation or infection. Cultures were obtained in 33 of the
      38 eyes operated on for worsening inflammation or infection and were positive in
      42%. Cultures obtained from the early additional procedures were positive more
      frequently in eyes with an initial TAP (71%) than in eyes with an initial VIT
      (13%). Both virulence of initial microbiologic organism isolated and poor
      presenting vision were risk factors for requirement of reoperation. In all cases
      in which a single organism was cultured at the initial procedure, when the
      reculture was positive, it was the same organism. Late additional procedures
      (after 7 days) were required in 27% of patients. Visual outcome was much worse
      for eyes that had an additional procedure compared to eyes that did not, and this
      was especially the case for eyes that had an early additional procedure. Only 15%
      of eyes that had an early additional procedure achieved 20/40 visual acuity as
      compared to 57% of eyes that did not. CONCLUSION: Need for an additional
      procedure was a marker of more severe disease, and patients who underwent
      additional procedures achieved poorer visual acuity at final follow-up.

PMID- 9544647
TI  - Hereditary external ophthalmoplegia synergistic divergence, jaw winking, and
      oculocutaneous hypopigmentation: a congenital fibrosis syndrome caused by
      deficient innervation to extraocular muscles.
AB  - BACKGROUND: The congenital fibrosis syndrome is a hereditary form of external
      ophthalmoplegia that is considered to be a primary myopathy. PURPOSE: To document
      the coexistence of two distinct forms of ocular motor synkinesis in a subgroup of
      patients with congenital fibrosis syndrome. METHODS: Clinical and intraoperative
      examination results and extraocular muscle biopsy specimens from four patients
      with congenital fibrosis syndrome were studied. RESULTS: Three patients displayed
      a variant of synergistic divergence characterized by simultaneous abduction with
      intorsion and depression of the synkinetically abducting eye. Three patients had
      variant of Marcus Gunn jaw winking characterized by elevation of a ptotic eyelid
      during mouth opening. Three patients had oculocutaneous hypopigmentation.
      CONCLUSIONS: A subgroup of patients with congenital fibrosis syndrome display two
      distinct synkinetic ocular movements in conjunction with oculocutaneous
      hypopigmentation. The patterns of neuronal misdirection implicate a regional
      innervational disturbance involving cranial nerves III through VI as the
      underlying cause of diffuse hereditary ophthalmoplegia in these patients.

PMID- 9544648
TI  - Comparative pupil dilation using phenylephrine alone or in combination with
      tropicamide.
AB  - OBJECTIVE: A prevalence survey of actinic and other eye diseases was conducted in
      Nambour, Queensland, Australia, in 1992. Pupils were dilated with phenylephrine
      alone for cataract identification because there were concerns that patient
      discomfort, due to cycloplegia occurring with the usual dilating agents of
      tropicamide and phenylephrine, may influence future compliance in an associated
      intervention study. This validation study was undertaken to measure the possible
      underestimation of cataract prevalence in this community study, which may have
      occurred because of inadequate dilation from phenylephrine alone. DESIGN: The
      study design was a repeated measures experimental design. PARTICIPANTS: Forty
      seven normal subjects participated in the study. Both eyes were tested.
      INTERVENTION: Pupil diameter after dilation with three drops of 10% phenylephrine
      alone was compared with pupil diameter after dilation with three drops of 10%
      phenylephrine together with three drops of 1% tropicamide. The two regimens were
      given to the same subjects 1 week apart. Reversal was attempted with thymoxamine
      hydrochloride 0.5%. MAIN OUTCOME MEASURES: Pupil diameter was assessed using a
      Neitz cataract camera, and accommodation reserve also was measured. Subjects'
      subjective appreciation of return of ocular function was assessed by a
      questionnaire. Repeated measures analysis of variance, paired t test, McNemar's
      test, and Wilcoxon signed rank test were used to analyze outcomes. RESULTS: Mean
      maximum pupil size with 10% phenylephrine and 1% tropicamide was significantly
      larger than pupil size after the use of 10% phenylephrine alone (F1,19 = 18.99, P
      = 0.0003). However, there was no significant difference between the two dilation
      regimens when comparing the proportion of subjects who dilated to 6 mm or more
      (McNemar's X(2)1 = 2.7, P > 0.1). Compared with 10% phenylephrine and 1%
      tropicamide, pupil diameters were significantly smaller (t46 = 16.77, P =
      0.0001), and accommodation reserve greater (t46 = 4.14, P = 0.0001), 40 minutes
      after reversal with thymoxamine in the group dilated with 10% phenylephrine
      alone. CONCLUSION: Pupil dilation with 10% phenylephrine alone, if allowed at
      least 40 minutes to act, will be as satisfactory for the identification of
      cataracts in a normal population as 10% phenylephrine and 1% tropicamide and is
      more acceptable because of reduced problems with glare and accommodation.

PMID- 9544649
TI  - The prevalence of glaucoma in the Melbourne Visual Impairment Project.
AB  - PURPOSE: The purpose of the study was to determine the prevalence of glaucoma in
      Melbourne, Australia. METHODS: All subjects were participants in the Melbourne
      Visual Impairment Project (Melbourne VIP), a population-based prevalence study of
      eye disease that included residential and nursing home populations. Each
      participant underwent a standardized eye examination, which included a Humphrey
      Visual Field test, applanation tonometry, fundus examination including fundal
      photographs, and a medical history interview. Glaucoma status was determined by a
      masked assessment and consensus adjudication of visual fields, optic disc
      photographs, intraocular pressure, and glaucoma history. RESULTS: A total of 3271
      persons (83% response rate) participated in the residential Melbourne VIP. The
      overall prevalence rate of definite primary open-angle glaucoma in the
      residential population was 1.7% (95% confidence limits = 1.21, 2.21). Of these,
      50% had not been diagnosed previously. Only two persons (0.1%) had primary angle
      closure glaucoma and six persons (0.2%) had secondary glaucoma. The prevalence of
      glaucoma increased steadily with age from 0.1% at ages 40 to 49 years to 9.7% in
      persons aged 80 to 89 years. There was no relationship with gender. The authors
      examined 403 (90.2% response rate) nursing home residents. The age standardized
      rate for this component was 2.36% (95% confidence limits = 0, 4.88). CONCLUSION:
      The rate of glaucoma in Melbourne rises significantly with age. With only half of
      patients being diagnosed, glaucoma is a major eye health problem and will become
      increasingly important as the population ages.

PMID- 9544650
TI  - The role of adjunctive mitomycin C in secondary glaucoma triple procedure as
      compared to primary glaucoma triple procedure.
AB  - OBJECTIVE: This study aimed to investigate whether previously failed glaucoma
      filtration surgery is a risk factor for filtration failure of subsequent
      trabeculectomy combined with cataract surgery and to determine the role of
      adjunctive mitomycin C (MMC) in the secondary glaucoma triple procedure (SGTP) as
      compared to primary glaucoma triple procedure (PGTP). DESIGN: A prospective,
      controlled study that was randomized with respect to assignment to adjunctive MMC
      and a case-control design with respect to comparisons between SGTP and PGTP was
      studied. PARTICIPANTS: The SGTP group consisted of 49 eyes of 49 consecutive
      patients with primary open-angle glaucoma with a history of glaucoma filtration
      surgery requiring glaucoma medical therapy and in need of cataract surgery,
      randomized to adjunctive MMC (SGTP MMC subgroup of 21 eyes) and no adjunctive MMC
      (SGTP control subgroup of 28 eyes). The PGTP group consisted of 49 PGTP cases
      closely matched to the SGTP cases with respect to age, race, gender, MMC use, C:D
      ratio, and systemic diseases. INTERVENTION: Trabeculectomy combined with
      phacoemulsification and a small incision (5 x 6 mm), all polymethylmethacrylate
      posterior chamber intraocular lens implantation with or without adjunctive MMC
      (0.5 mg/ml for 1 minute), was performed. MAIN OUTCOME MEASURES: Surgery failure
      was defined as the need of an additional intraocular procedure or the need of
      more than one medication to achieve intraocular pressure control to the target
      level. Intragroup and intergroup comparisons were made with respect to filtration
      outcome among the SGTP and PGTP patients. RESULTS: Without adjunctive MMC,
      filtration success was significantly less in SGTP than in PGTP (P = 0.03).
      Adjunctive MMC significantly increased the success rate of SGTP (P = 0.02) but
      not that of PGTP (P = 0.89) over the average follow-up period of 2 years.
      CONCLUSIONS: Previously failed glaucoma filtration surgery is a significant risk
      factor for the filtration failure of combined surgery. Intraoperative use of
      adjunctive MMC significantly improves the filtration success rate of SGTP.

PMID- 9544651
TI  - An ultrasound biomicroscopic study of eyes after deep sclerectomy with collagen
      implant.
AB  - OBJECTIVE: This study aimed to assess the natural history of eyes after deep
      sclerectomy with collagen implant (DSCI), a nonperforating glaucoma-filtering
      surgery. DESIGN: The design was a prospective, longitudinal, observational, and
      nonrandomized study. PARTICIPANTS: Forty-five eyes of 41 patients with medically
      uncontrolled open-angle glaucoma were studied. INTERVENTION: Deep sclerectomy
      with collagen implant was performed. MAIN OUTCOME MEASURES: Ultrasound
      biomicroscopy (UBM) of the sclerectomy site was performed 1, 2, 3, 6, 9, 12, and
      18 months after surgery. The following parameters were assessed: length and
      height of the collagen implant, thickness of the residual trabeculodescemetic
      membrane, and bleb appearance. RESULTS: Mean intraocular pressure decreased from
      a preoperative value of 26.3 +/- 3.5 mmHg (mean +/- standard deviation) to a
      postoperative value of 16.6 +/- 3.1 mmHg (mean +/- standard deviation) at 18
      months (P < 0.001). The UBM findings showed a subconjunctival filtration with a
      nonperforated thin trabeculodescemetic membrane. In 23 eyes (51%), a hypoechoic
      area in the suprachoroidal space was observed. The thickness of the
      trabeculodescemetic membrane was stable throughout the study with a mean value of
      0.13 mm +/- 0.02 (mean +/- standard deviation) at 18 months. The collagen implant
      dissolved slowly within 6 to 9 months, leaving a tunnel in the sclera.
      CONCLUSIONS: The UBM findings are consistent with intraocular pressure lowering
      by aqueous filtration through the thin remaining trabeculodescemetic membrane to
      an area under the scleral flap, which was maintained open by the collagen
      implant. The authors speculate that aqueous humor then reached the
      subconjunctival space and, eventually, was filtered through the thin scleral wall
      into the suprachoroidal space. Complete resorption of the collagen implant
      occurred between 6 and 9 months after surgery.

PMID- 9544652
TI  - Glaucoma associated with keratoprosthesis.
AB  - OBJECTIVE: This study aimed to review the authors clinical experience with
      glaucoma associated with keratoprosthesis in patients with severe corneal
      disease. DESIGN: The study design was a retrospective review of case series.
      PARTICIPANTS: The authors studied 55 eyes in 52 patients with keratoprostheses
      with follow-up of 21 +/- 16 months (range, 3-77 months). INTERVENTION: Glaucoma
      drainage devices were implanted in 36 eyes (35 Ahmed valves, 1 Krupin valve) with
      21 +/- 15 months' follow-up (range, 3-64 months). MAIN OUTCOME MEASURES: Clinical
      outcome assessment included vision, intraocular pressure (IOP), visual fields,
      optic disc appearance, and identification of complications. RESULTS: Glaucoma was
      found in the majority (64%) of eyes treated with keratoprostheses, identified in
      20 eyes (36%) before surgery and an additional 15 eyes (28%) after surgery. Of
      the 36 eyes treated with glaucoma drainage devices, IOP was controlled in 29 eyes
      (81%), with 9 eyes (25%) requiring additional medications. Continued progression
      of glaucoma occurred in 5 (14%) of 36 eyes with keratoprostheses and glaucoma
      drainage implants (4 of these eyes had advanced glaucomatous optic nerve damage
      before surgery). There were nine nonvision-threatening complications due to
      drainage implants. Compared with the preoperative visual acuity, vision was
      markedly improved in 63%, unchanged in 17%, and worse in 20% of eyes after
      keratoprosthesis surgery. CONCLUSION: Elevation of IOP is common in patients with
      keratoprosthesis, and prevention or treatment with glaucoma drainage implants is
      effective.

PMID- 9544653
TI  - New isotope production company gearing up for nuclear medicine industry.

PMID- 9544654
TI  - Investing in the future: MDS Nordion's Maple Medical Isotope Reactor Project.

PMID- 9544655
TI  - Accelerator production of tritium as a future source of medical radionuclides.

PMID- 9544656
TI  - Nuclear medicine pioneer: Joseph F. Ross. Focus and determination melded nuclear
      medicine into recognized specialty.

PMID- 9544657
TI  - Update on ambulatory payment classifications.

PMID- 9544658
TI  - SNM house of delegates approves physician supervision guidelines; HCFA delays
      physician supervision rule.

PMID- 9544659
TI  - Prognostic value of myocardial perfusion imaging with exercise and/or
      dipyridamole hyperemia in patients with preexisting left bundle branch block.
AB  - The detection of myocardial ischemia in patients with preexisting left bundle
      branch block (LBBB) remains problematic. Pharmacologic hyperemia with
      dipyridamole is now used routinely in such patients for detection of significant
      coronary artery disease. Little data exists on the prognostic value of cardiac
      nuclear scintigraphy in patients with preexisting LBBB. The purpose of our study
      was to determine the prognostic value of cardiac nuclear scintigraphy in patients
      with preexisting LBBB. METHODS: Ninety-six patients with preexisting LBBB
      underwent perfusion imaging between July 1987 and June 1995. Thirty-seven
      underwent planar 201Tl imaging, and 59 underwent SPECT sestamibi imaging. Images
      were interpreted by consensus of two experienced observers and classified as
      normal, abnormal low risk and abnormal high risk. Outcomes measured were
      survival, cardiac and noncardiac death. The final study group included 43 women
      and 53 men, aged 42-83 (mean 66 +/- 9). Average follow-up was 3.4 +/- 2.1 yr.
      RESULTS: Of the 96 patients examined, 31 had normal scans, 39 had low-risk scans
      and 26 had high-risk scans. At the end of the study period, 27 patients with
      normal scans were still alive while 2 suffered cardiac death and 2 suffered
      noncardiac death. Of those with low-risk scans, 36 survived while 2 suffered
      cardiac death and 1 suffered noncardiac death. Finally, of those with high-risk
      scans, 17 survived while 8 suffered cardiac death and 1 suffered noncardiac death
      (chi-square test, p = 0.020). CONCLUSION: Dipyridamole imaging is an important
      prognostic tool for predicting future cardiac events in patients with preexisting
      LBBB and aids in their risk stratification for coronary artery disease.

PMID- 9544660
TI  - Myocardial tomography with technetium-99m-tetrofosmin during intravenous infusion
      of adenosine triphosphate.
AB  - The purpose of this study was to determine the biodistribution of 99mTc
      tetrofosmin during intravenous infusion of adenosine triphosphate (ATP) and to
      evaluate the potential diagnostic value of myocardial tomography with 99mTc
      tetrofosmin during ATP infusion for the detection of coronary artery disease.
      METHODS: Myocardial 99mTc-tetrofosmin imaging with ATP infusion and coronary
      arteriography were performed on 65 patients with suspected coronary artery
      disease. ATP was infused intravenously at a rate of 0.16 mg/kg/min for 5 min, and
      370 MBq of 99mTc-tetrofosmin was injected 3 min after the start of ATP infusion.
      Myocardial SPECT imags were obtained 60 min later. Then, 740 MBq of 99mTc
      tetrofosmin was administered at rest, and myocardial SPECT was repeated. Regional
      uptakes of 99mTc-tetrofosmin were scored from 4, normal, to 0, no activity.
      Serial 5-min planar images were obtained in the anterior projection at 15, 30, 45
      and 60 min after the 99mTc-tetrofosmin injection in 10 patients. Heart-to-lung
      and heart-to-liver count ratios were defined from the serial planar images.
      RESULTS: Adverse effects of ATP infusion were mild and transient. A heart-to-lung
      ratio after ATP infusion was high even at 15 min (3.40 +/- 0.33) and gradually
      increased with time. A heart-to-liver ratio after ATP was 0.53 +/- 0.40 at 15 min
      and increased with time. A heart-to-liver ratio reached 0.99 +/- 0.25 (p < 0.01)
      after 45 min and 1.32 +/- 0.36 (p < 0.01) after 60 min. The sensitivity and
      specificity for detecting coronary artery disease by myocardial SPECT with ATP
      were 89% (39/44) and 86% (18/21), respectively. CONCLUSION: This study shows the
      favorable biodistribution of 99mTc-tetrofosmin after intravenous infusion of ATP.
      A one-day imaging protocol of 99mTc-tetrofosmin tomography with ATP is feasible
      and has high diagnostic accuracy for coronary artery disease.

PMID- 9544661
TI  - The effect of coronary artery bypass surgery on brain perfusion.
AB  - Coronary artery bypass grafting (CABG) is one of the major treatment methods of
      coronary artery disease. CABG is an open-heart surgery that uses cardiopulmonary
      bypass (CPB). After CPB, it is well known that neurological and
      neuropsychological complications may occur. The purpose of this study was to
      evaluate brain perfusion patterns before and after CPB and to locate brain
      perfusion changes in patients with neurological and neuropsycological
      complications after CPB. METHODS: Twenty-five patients who underwent open-heart
      surgery (22 CABG, 3 valve replacement) and 5 patients (4 cholecystectomy, 1
      periferic vascular surgery) as a control group were included in the study. The
      99mTc-HMPAO injected dose was 925 MBq. Brain perfusion SPECT images were obtained
      30-60 min postinjection using a dedicated triple-head brain SPECT camera. Imaging
      was performed 1 wk before and 4-6 wk after surgery. Technetium-99m-HMPAO brain
      SPECT slices were evaluated visually and semiquantitatively. RESULTS: None of the
      patients had severe neurologic complications. Neuropsychological deficits
      occurred in eight patients after CABG. Cognitive deterioration and depressive
      mood occurred in five patients. Disorientation, agitation and confusion periods
      were present in another two patients. Frontal hypoperfusion was found in these
      patients by visual and semiquantitative evaluations (p = 0.0277) and left
      parietal hypoperfusion was also present semiquantitatively (p = 0.0277). Visual
      hallucinations occurred in one patient. Computed tomography of these patients was
      normal. No perfusion abnormalities were observed in the patient with visual
      hallucinations and in patients without symptoms after open-heart surgery nor in
      the control group. Brain SPECT was repeated in two symptomatic patients 5 mo
      after CABG. Frontal hypoperfusion became normal, and these patients' symptoms
      disappeared. CONCLUSION: The results of this study indicate that regional
      cortical hypoperfusion may occur in patients with neuropsychological
      complications after CABG. Technetium-99m-HMPAO brain SPECT is a useful method to
      locate and determine brain perfusion changes after CABG.

PMID- 9544662
TI  - Dual spillover problem in the myocardial septum with nitrogen-13-ammonia flow
      quantitation.
AB  - Conventional cardiac PET modeling techniques for [13N]ammonia flow determination
      do not fully account for the effects of spillover of activity from the right
      ventricle (RV) onto the activity in the myocardial septum. The purpose of this
      study was to investigate and to quantitatively account and correct for this
      effect. METHODS: Simulations were performed to determine the error introduced by
      conventional quantitation using septal time-activity curves, which only account
      for left ventricle (LV) spillover. Furthermore, we explored two separate methods
      to account for the dual spillover problem: direct estimation of the RV and LV
      spillover fractions incorporated into the [13N]ammonia model by using the LV and
      RV input functions in the fit and estimation of the relative dispersion and time
      shift between the LV and RV input functions by fitting using only the LV input
      function. The simulated curves were fitted using a two-compartment [13N]ammonia
      model. Flow estimates from the conventional model and the models including either
      of the two correction procedures were compared with canine microsphere data.
      RESULTS: The influence of RV spillover on flow estimation in the septum is
      determined by several parameters (e.g., dispersion between the RV and LV input
      function). Depending on the value of these parameters, the septal flow may be
      underestimated by 0%-30%. The applied methods for correction of the dual
      spillover problem were comparable and allow for more accurate quantitation in the
      septum. The canine microsphere data revealed that flow underestimation in the
      septum is small but significant. CONCLUSION: Dual spillover in the myocardial
      septum can introduce significant errors in the estimation of flow by the
      conventional [13N]ammonia model fitting method, which does not properly account
      for the RV spillover. Adjusting for the RV spillover in one of the two proposed
      methods allows for more accurate quantitation of myocardial septal flow with
      [13N]ammonia PET data.

PMID- 9544663
TI  - Direct detection of regional myocardial ischemia with technetium-99m
      nitroimidazole in rabbits.
AB  - Conventional perfusion scintigraphy assesses disparities in regional myocardial
      blood flow but does not directly detect hypoxic tissue. Nitroimidazoles labeled
      with positron-emitting radionuclides have recently shown promise as direct
      markers of myocardial hypoxia. This study evaluates a new 99mTc-labeled
      nitroimidazole of potential benefit in standard myocardial scintigraphy. METHODS:
      Technetium-99m-labeled nitroimidazole was administered to rabbits during the
      early reperfusion phase after 10 min (Group 1) or 60 (Group 2) min of coronary
      occlusion or after 10 min of a fixed coronary occlusion (Group 3). Tracer
      retention at 1 hr was assessed in relation to microsphere-determined blood flow
      during coronary occlusion and at tracer injection. The pattern of nitroimidazole
      retention on autoradiographs was then compared with the pattern of myocardial
      hypoperfusion defined by fluorescein photography to precisely define tracer
      localization. RESULTS: The retention of nitroimidazole in Group 1 rabbits (brief
      occlusion) was independent of both occlusion and reperfusion blood flow and was
      uniformly distributed on the autoradiographs. In contrast, nitroimidazole
      retention in Groups 2 and 3 increased with the severity of hypoperfusion during
      the occlusion phase and precisely delineated the ischemic zone on all
      autoradiographs. CONCLUSION: This 99mTc-labeled hypoxia-avid tracer delineates
      severe ischemia even after blood flow to the compromised myocardium has been
      restored. This class of compounds can potentially enhance the physiological
      assessment of patients with ischemic heart disease.

PMID- 9544664
TI  - Hypofrontality and negative symptoms in major depressive disorder.
AB  - The purpose of the current study was to compare regional cerebral blood flow
      (rCBF) in patients with major depressive disorder (MDD) to that of healthy
      subjects and to examine the relationship between rCBF, depressive symptoms (DS)
      and negative symptoms (NS) in these patients. METHODS: Eleven psychiatric
      inpatients with diagnosed (MDD) and 15 normal control subjects were administered
      the scale for the assessment of negative symptoms (SANS) and the modified
      Hamilton rating scale for depression with items descriptive of NS excluded (HRSD
      DS). Each patient underwent a SPECT scan using 99mTc-HMPAO at rest. Cortical and
      subcortical regions of interest (ROIs) were symmetrically defined in each
      hemisphere. Cortical-to-cerebellar perfusion ratios were established
      quantitatively using ADAC software. RESULTS: Subjects in the MDD group had
      significantly lower rCBF in the frontal cortex and cinglulate gyrus (MANOVA, p =
      0.038) due to differences in dorsolateral prefrontal cortex bilaterally (right F
      = 7.69, p = 0.01; left F = 8.41, p = 0.01) in the right orbitofrontal cortex (F =
      6.79, p = 0.02) and in the cingulate gyrus (F = 5.34, p = 0.03). The MDD group
      also had lower rCBF in the posterior cortical structures (MANOVA, p = 0.072),
      which was due to decreased perfusion in the right parietal cortex (F = 7.54, p =
      0.01). There were negative correlations between the SANS total score and rCBF in
      both the left dorsolateral prefrontal cortex (Pearson's correlation coefficient r
      = .-67, p < 0.05) and the left anterior temporal cortex (r = -0.71, p < 0.01) in
      MDD patients. Additionally, there were positive correlations between HRSD scores
      and rCBF in the left anterior temporal (r = 0.71, p < 0.01), left dorsolateral
      prefrontal (r = 0.70, p < 0.01), right frontal (r = 0.82, p < 0.01) and right
      posterior temporal (r = 0.74, p < 0.01) cortices. Cerebral blood flow was not
      correlated with either mini-mental state examination scores or age. CONCLUSION:
      This preliminary study replicates the finding of hypofrontality in MDD and
      indicates that decreased perfusion is associated specifically with negative
      symptom severity. These results support the hypothesis that, in MDD, negative
      symptoms and symptoms of depression are distinct phenomena and underscore the
      importance of negative symptom evaluation in neuroimaging studies of MDD and
      other disorders.

PMID- 9544665
TI  - Imaging of cerebral blood flow with technetium-99m-HMPAO and technetium-99m-ECD:
      a comparison.
AB  - Because 99mTc-HMPAO and 99mTc-ECD are both used for SPECT imaging of cerebral
      blood flow, the question arises whether there are any differences in their
      respective regional cerebral distribution. For that purpose, visual and
      semiquantitative comparisons between 99mTc-HMPAO and 99mTc-ECD studies were
      performed. METHODS: Seventeen patients (4 women; 13 men; age 45-89 yr; mean age
      71 yr) with various neurological diseases, except acute/subacute stroke, were
      investigated twice with 99mTc-HMPAO and 99mTc-ECD using a triple-headed rotating
      SPECT camera. After image reorientation, the two studies were evaluated visually.
      Seventy regions of interest (ROIs) were drawn manually and the same set of ROIs
      was applied in both studies. Regional indices (RI) normalized to individual brain
      values were calculated and first compared between two random patient groups.
      Second, for all patients, RI for 70 and later for 27 regions (gained after
      summing values of corresponding regions in different brain slices) were compared
      by using a paired Student's t-test applying Bonferroni's correction. RESULTS:
      Visual evaluation demonstrated relatively high 99mTc-ECD uptake in occipital and
      comparatively low uptake in mediotemporal regions. Calculation of RI revealed
      significantly higher values in the right cerebellum, brainstem, mediotemporal
      regions, right basal ganglia and the thalamus in the 99mTc-HMPAO SPECT studies
      and higher values in the occipital, supratemporal/inferior parietal and parietal
      cortex in the 99mTc-ECD SPECT studies, respectively. CONCLUSION: Significant
      differences in regional tracer distribution between 99mTc-HMPAO and 99mTc-ECD
      could be detected, probably caused by different tracer kinetics. The results
      indicate that direct comparisons of studies performed with 99mTc-HMPAO and 99mTc
      ECD are not possible and the use of either tracer can be favorable in different
      clinical questions.

PMID- 9544666
TI  - Technetium-99m-ECD brain SPECT in cerebral palsy: comparison with MRI.
AB  - Hypoxic brain injury is one of the major causes of cerebral palsy. Therefore,
      this study was performed to evaluate cerebral perfusion impairments in these
      patients using 99mTc-ECD brain SPECT. METHODS: Fifty-one patients (31 boys, 20
      girls; age range 6 mo to 6 yr, 11 mo) with clinical manifestations of cerebral
      palsy underwent brain SPECT after intravenous injection of 99mTc-ECD. The
      clinical subtypes of cerebral palsy were spastic diplegia (n = 35), spastic
      quadriplegia (n = 11), spastic hemiparesis (n = 2), choreoathetoid (n = 2) and
      mixed (n = 1). Transaxial, coronal and sagittal images obtained with a brain
      dedicated annular crystal gamma camera were qualitatively analyzed and compared
      with the findings of magnetic resonance imaging (MRI). RESULTS: In SPECT,
      thalamic hypoperfusion was seen in all patients except one (98%), followed by
      hypoperfusion in the temporal lobe (52.9%, n = 27), basal ganglia (41.2%, n =
      21), cerebellum (39.2%, n = 20) and extratemporal cortices (21.6%, n = 11).
      However, MR imaging demonstrated thalamic abnormality in seven (13.7%), basal
      ganglia in two (3.9%), extratemporal cortical defect in five (9.8%) and
      cerebellar atrophy in one (1.9%). Instead, white matter changes such as
      periventricular leukomalacia or ischemia (56.9%, n = 25) and thinning of corpus
      callosum (49%, n = 25) were the major findings. CONCLUSION: Brain SPECT is useful
      in the diagnosis of cerebral palsy and is more sensitive in the detection of
      cortical, subcortical nuclei and cerebellar abnormalities. MRI is superior in the
      detection of white matter changes.

PMID- 9544667
TI  - Technetium-99m-HMPAO in Tourette's syndrome on neuroleptic therapy and after
      withdrawal.
AB  - Both decreased and increased perfusion and metabolism have been described with
      PET and SPECT in different areas of the brain in patients with Gilles de la
      Tourette's syndrome. The aim of this study was to define the regional cerebral
      perfusion pattern in drug-free patients and the changes in perfusion with the
      usual neuroleptic treatment. METHODS: A group of 13 normal control subjects and
      15 unmedicated Gilles de la Tourette's syndrome patients were studied with 99mTc
      HMPAO brain SPECT. Thirteen of the initial group of patients were retested on
      neuroleptic treatment. A semiquantitative analysis of the images was performed.
      RESULTS: Decreased perfusion in orbital and anterior medial regions of both
      frontal lobes as well as in both temporal lobes was observed in the nontreated
      group compared with control subjects. With treatment, a perfusion increase in
      these frontal regions and in the left medial temporal cortex was observed.
      CONCLUSION: Neuroleptic treatment could decrease the hyperactivity of the
      dopaminergic system leading to improvement of the clinical symptoms and
      reperfusion of some previously hypoperfused regions.

PMID- 9544668
TI  - Cerebral perfusion imaging in asymptomatic carotid artery occlusion following gun
      shot.
AB  - Recognition of brain injury in asymptomatic carotid artery injuries with
      conventional methods can be difficult. We present a case of angiographically
      proven asymptomatic left internal carotid artery occlusion with normal CT after a
      gunshot wound. The SPECT brain perfusion imaging showed mild generalized
      supratentorial hypoperfusion of the bilateral cerebral cortices on the left side
      and severe left temporal lobe hypoperfusion.

PMID- 9544669
TI  - Cerebral perfusion impairment in a patient with toluene abuse.
AB  - We report the case of a 17-yr-old man diagnosed as a toluene abuser. He had an 8
      mo history of toluene inhalation exposure and was admitted to this hospital with
      symptoms of auditory and visual hallucination. Magnetic resonance imaging (MRI)
      revealed no structural abnormalities both on T1- and T2-weighted images, whereas
      SPECT using 99mTc-ethyl cysteinate dimer (ECD) showed multifocally decreased
      perfusion in the cerebral cortex, basal ganglia and thalami. Our case indicates
      that SPECT detects early central nervous system injury from toluene inhalation
      even when neurological examination and neuroanatomic imaging such as MRI are
      normal.

PMID- 9544670
TI  - In vivo detection of malignant thymic masses by indium-111-DTPA-D-Phe1-octreotide
      scintigraphy.
AB  - Many tumors with neuroendocrine characteristics express high amounts of
      somatostatin receptors that enable in vivo imaging with [(111)In-DTPA-D-Phe1]
      octreotide. In this study, we have analyzed the feasibility in detecting and
      characterizing thymic masses by somatostatin receptor scintigraphy (SRS).
      METHODS: Eighteen patients (13 women, 5 men, ages 18-78 yr; mean +/- s.d. = 42.1
      +/- 17.6 yr) were enrolled in this study. Eleven patients were studied during
      diagnosis and seven during routine follow-up. In seven patients, myasthenia
      gravis was the presenting symptom. SRS was performed within 4 wk after CT and/or
      MRI. Planar and tomographic images were acquired within 24 hr after the injection
      of approximately 111 MBq of [(111)In-DTPA-D-Phe1]-octreotide. The scintigraphic
      results were categorized according to the histologic findings. RESULTS: Histology
      diagnosed 10 mixed epithelial/lymphoid thymomas (8 with prevalent epithelial
      component), 2 thymic carcinomas, 1 thymic carcinoid, 1 lymphangioma and 4 thymic
      hyperplasias. Two thymoma were Stage I, 3 were Stage II, 2 were Stage III and 5
      were Stage IV, as was the thymic carcinoid. Indium-111-DTPA-D-Phe1-octreotide
      concentrated in primary and/or metastatic sites of thymic tumors, thereby
      enabling successful external gamma imaging of sites greater than 1.5 cm in size.
      Tumor-to-lung (T/L) ratios were as high as 7.6-fold (range 1.7-7.6). Untreated
      thymomas showed higher T/L (4.34 +/- 1.57) than treated ones (2.68 +/- 1.18). No
      uptake was detectable in the four patients with benign thymic hyperplasia and the
      patient with the lymphangioma. CONCLUSION: Indium-111-DTPA-D-Phe1-octreotide is
      avidly concentrated within thymic tumors, but it is not concentrated by thymic
      hyperplasia, which allows differential diagnosis. Thus, in patients with
      myasthenia gravis, SRS may have a role in characterizing thymic masses, thereby
      overcoming the limits of cross-sectional imaging modalities.

PMID- 9544671
TI  - Combined fluorine-18-FDG and carbon-11-methionine PET for diagnosis of tumors in
      lung and mediastinum.
AB  - We evaluated the value of PET using 18F-fluorodeoxyglucose (FDG) and 11C
      methionine, individually or in combination, to distinguish malignant from benign
      tumors and to identify or exclude mediastinal metastases. METHODS: Seventeen
      patients with a tumor in the lung or mediastinum were evaluated with 18F-FDG and
      11C-methionine PET. For morphological comparison, we used CT, and all findings
      were confirmed by histology of surgical resection specimens (n = 16) or by
      cytology (n = 1). RESULTS: All tumors were visualized equally well with both
      tracers, and there were no false-positive results. In 2 patients with a malignant
      tumor, coexisting pneumonia was correctly diagnosed as an inflammatory lesion
      because of its wedge-like shape. PET correctly excluded hilar invasion and
      mediastinal lymph node metastases in 10 of 14 patients with primary lung tumor.
      PET identified mediastinal metastases in 4 of 4 patients. CT failed to detect
      mediastinal tumor spread in 2 patients and gave a false-positive reading in 2
      others. Significantly higher uptake (SUV) and transport rate (slope) values were
      obtained from malignant than benign lesions with both tracers. No major
      differences were seen in either the levels of significance or accuracy when the
      two tracers were compared. Slope values did not add further information to what
      was obtained with SUV. Density correction of SUV and slope values, to avoid the
      influence of surrounding air as well as tumor heterogeneity, increased these
      differences somewhat. Both tracers distinguished malignant from benign lesions
      with a 93% sensitivity and an accuracy of 89%-95%, but sensitivity improved to
      100% when values from both tracers were combined. CONCLUSION: Fluorine-18-FDG and
      11C-methionine PET visualized all tumors equally well and detected mediastinal
      spread better than CT. For differentiation purposes, the problems of false
      positive and false-negative PET findings could not be safely overcome in a
      limited number of cases either by the use of both tracers, by the additional use
      of slope values or by lesion density correction.

PMID- 9544672
TI  - Iodine-131-metaiodobenzylguanidine uptake in metastatic carcinoid tumor to the
      orbit.
AB  - Metastatic tumor is one of several etiologies of space-occupying masses in the
      orbit that accounts for 1%-13% of all orbital masses (1). In the adult patient
      population, breast cancer is the most common tumor to metastasize to the orbit
      followed by metastases from the lung, prostate and gastrointestinal tract (2). It
      is rare for carcinoid tumors to metastasize to the eye or to the orbit. Carcinoid
      tumors arise from Kulchitsky cells that originate in the neural crest.
      Histologically, these tumors resemble, but are not as aggressive as,
      adenocarcinomas. Most carcinoids arise in the gastrointestinal tract or the lung.
      The most common site for carcinoid metastases is the liver. On anatomical imaging
      studies, such as CT and magnetic resonance imaging, metastatic orbital carcinoid
      tumors appear as nonspecific tumor masses. Carcinoid tumors have an affinity for
      uptake of the radiopharmaceutical 131I-metaiodobenzylguanidine (MIBG) (3). We
      report a case of a patient with a known carcinoid tumor who developed a left
      orbital mass that demonstrated abnormal uptake of 131I-MIBG indicative of
      metastatic carcinoid tumor to the orbit.

PMID- 9544673
TI  - Prostate cancer abdominal metastases detected with indium-111 capromab pendetide.
AB  - To provide appropriate therapy for prostate cancer, accurate staging of the
      patient's disease is essential. Determination of tumor size, location,
      periprostatic extension and metastatic disease in the skeleton and soft tissue
      are needed to stage properly. Current diagnostic modalities may lead to
      understaging in 40%-70% of prostate cancer. Detection of metastatic disease, both
      at the time of initial diagnosis and in patients with suspected local recurrence,
      can significantly alter the type of therapy given. Clinical studies using the
      (111)In radiolabeled immunoconjugate, MAb 7E11-C5.3-GYK-DTPA (capromab
      pendetide), have shown the superiority of radioimmunoscintigraphy over other
      diagnostic modalities in the detection of both primary and metastatic prostate
      cancer. Radioimmunoscintigraphy with capromab pendetide depends on expression of
      tumor-associated antigen rather than lesion size. Earlier detection of
      extraprostatic invasion and metastases by means of radioimmunoscintigraphy
      provides valuable information for treatment decisions. A case of metastatic
      prostate cancer in the abdomen of a patient without local disease, in which the
      extent of disease was confirmed at autopsy after sudden cardiac arrest, is
      presented.

PMID- 9544674
TI  - Capromab pendetide imaging of occult lymph node metastases.

PMID- 9544675
TI  - Fluorine-18-fluorodeoxyglucose dual-head gamma camera coincidence imaging of
      recurrent colorectal carcinoma.
AB  - We report our experience with coincidence detection imaging of 18F
      fluorodeoxyglucose (FDG) using a dual-head gamma camera. Scanning of the pelvis
      and abdomen of a patient with recurrent colorectal carcinoma showed recurrent
      disease in the pelvic floor and the base of the urinary bladder and metastatic
      disease in the retroperitoneal space of the pelvis. Although the tumor involving
      the bladder and pelvic floor was detected by CT and magnetic resonance imaging
      (MRI), metastatic spread to the retroperitoneal nodes on the left side was
      detected only by 18F-FDG imaging. Based on the ultrasound, CT, MRI and
      cystoscopy, a local recurrence of cancer was presumed in our patient. An
      exploratory laparotomy was performed to resect the tumor in its entirety. At the
      time of surgery, the retroperitoneal metastasis in the pelvis was confirmed. Had
      the findings of the coincidence detection imaging study been considered, the
      patient would have been spared the surgical procedure.

PMID- 9544676
TI  - Accumulation of iodine-131-iodocholesterol in renal cell carcinoma adrenal
      metastases.
AB  - Adrenocortical scintigraphy is a useful technique for differentiating between
      types of nonhyperfunctioning adrenal masses. Metastatic tumors do not normally
      accumulate radioiodocholesterol and show discordant uptake on scintigrams. We
      present two patients who showed accumulation of 131I-6beta-iodomethyl-19
      norcholesterol (NP59) in the adrenal metastases from renal cell carcinoma. In one
      patient with bilateral adrenal metastases, accumulation in the primary tumor as
      well as adrenal metastases was demonstrated. The adrenal metastases in both
      patients were resected and were histologically proven to be metastases from clear
      cell renal carcinoma. Accumulation of NP59 in metastatic adrenal tumors, although
      a very rare finding, suggests a pitfall in the differential diagnosis of adrenal
      cortical tumors.

PMID- 9544677
TI  - Rhenium-188(Sn)HEDP for treatment of osseous metastases.
AB  - Rhenium-188 (tin) hydroxyethylidine diphosphonate [188Re(Sn)HEDP] is a new
      radiopharmaceutical that localizes in skeletal metastases and emits beta
      particles that may be therapeutically beneficial. METHODS: It was evaluated by in
      vitro and in vivo testing in the laboratory, in animals and in humans using 188Re
      from a variety of sources. It may be produced by a desk-top method developed
      previously for 186Re(Sn)HEDP using 188Re produced through neutron irradiation of
      either enriched 187Re or naturally occurring rhenium targets or the use of a
      188W/188Re generator. RESULTS: So long as the mass of rhenium in the 188Re
      perrhenate to be processed into 188Re(Sn)HEDP is at least 100 microg,
      satisfactory radiochemical yields and purity may be obtained by all methods. The
      188Re(Sn)HEDP has biodistribution and radiation dosimetry characteristics that
      are similar to those noted previously for 186Re(Sn)HEDP and appears to result in
      similar benefits and toxicities in patients with skeletal metastases. External
      radiation exposure monitoring indicates that, only 4 hr after a therapeutic
      administration of 1110 MBq (30 mCi) of 188Re(Sn)HEDP, average exposure rates at 1
      meter from the patient would be only 0.5 mR/hr. CONCLUSION: Same-day, on-demand,
      outpatient therapy of disseminated skeletal metastases appears to be feasible
      with 188Re(Sn)HEDP.

PMID- 9544678
TI  - Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a
      potential tumor-detecting agent.
AB  - Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT agent for
      imaging amino acid uptake in tumors. We developed L-[3-(18)F]-alpha-methyl
      tyrosine (FMT) for PET studies. The aim of this study was to investigate its
      potential use as a tumor-detecting agent by using tumor-bearing mice. METHODS: We
      investigated the biodistribution in normal BALB/C mice and BALB/cA nude mice
      bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT
      tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPM11788 B
      cell lymphoma and MCF7 mammary cell carcinoma was assessed, and the results were
      compared with 18F-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The effect of
      competitive inhibition of large neutral amino acid transport system using
      unlabeled L-alanine was also investigated. RESULTS: The amount of FMT in blood
      fell to 1.05%ID/20 g at 60 min postinjection, whereas that in the pancreas was
      15.2%ID/20 g, resulting in a high pancreas-to-blood ratio of 14.5. In other
      organs, initial uptake peaked at 5 min postinjection and then declined with time.
      In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min
      postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94
      and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake of FMT
      was clearly reduced by inhibition of the amino acid transport system. In mice
      with LS180 and MCF7 tumors, FMT tumor uptake at 60 min postinjection was
      significantly higher than FDG tumor uptake, whereas in RPM11788 lymphoma, uptake
      of FDG was significantly higher than FMT tumor uptake. Tumor-to-blood ratios of
      FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were
      1.82, 5.88 and 3.56, respectively. CONCLUSION: FMT, like other fluorinated amino
      acids, may become a promising tumor-detecting agent for PET, assuming that
      efficient methods of radiosynthesis are developed.

PMID- 9544679
TI  - Effects of radiolysis on yttrium-90-labeled Lym-1 antibody preparations.
AB  - The physical half-life of 2.6 days and 2.2 MeV beta emissions of 90Y provide
      excellent properties for radioimmunotherapy applications. However, the clinically
      useful beta particles may be a source of radiation-induced damage of 90Y-labeled
      immunoconjugate radiopharmaceuticals during preparation or short-term storage.
      The stability of 90Y-labeled Lym-1 antibody was studied in standard radiopharmacy
      conditions to establish a formulation at which radiolysis is not a problem.
      METHODS: Lym-1-21T-BAD immunoconjugate intermediate was prepared according to our
      standard procedure, then labeled with 90Y at 1, 2, 4 and 9.4 mCi/mg Lym-1 using
      0.5 M tetramethylammonium acetate, pH 7, labeling buffer. Each mixture was
      challenged in diethylenetriaminepentaacetic acid to remove nonspecifically bound
      90Y. The 90Y-21T-BAD-Lym-1 products were purified by centrifuged molecular
      sieving column chromatography. The radiochemical purity and immunoreactivity of
      each preparation was monitored daily by high-performance liquid chromatography
      (HPLC) and solid-phase radioimmunoassay, respectively, for 3 days. The
      preparation at 2 mCi/mg was also formulated in 4% (wt/vol) human serum albumin
      (HSA) overall and at 9.4 mCi/mg in five-fold water, 4 and 10% (wt/vol) HSA
      overall; all were monitored as above. RESULTS: The monomeric quality and purity
      profile of products at 1 and 2 mCi/mg were retained (> or = 80%) as was their
      immunoreactivity (> or = 75%) over 3 days. The radiochemical purity and
      immunoreactivity of the product at 4 mCi/mg declined to 65% and 28%,
      respectively, by 3 days after preparation and in just 48 hr, the product at 9.4
      mCi/mg had degraded to 21% in radiochemical purity with only 3% immunoreactivity.
      The current HPLC data and earlier published chromatographic evidence did not
      support a compromised radiochemical integrity of 90Y-DOTA complexes by loss of
      90Y from the DOTA chelate. CONCLUSION: Radiolysis of 90Y-labeled antibody
      preparations did not appear to be a problem at 90Y-21T-BAD-Lym-1 products < or =
      2 mCi/mg. Human serum albumin proved to be an effective radioprotectant as the
      initial 100% immunoreactivity of the product at 2 mCi/mg was retained for 72 hr.
      The results underscore the need for appropriate formulations and dilutions of
      clinical doses of 90Y immunopharmaceuticals immediately after manufacture.

PMID- 9544680
TI  - Radiation absorbed dose estimates for indium-111-labeled B72.3, an IgG antibody
      to ovarian and colorectal cancer: MIRD dose estimate report No. 18.

PMID- 9544681
TI  - CuTira brachytherapy: a new combination of radioactive copper isotopes and the
      hypoxic cytotoxin, tirapazamine, for targeted tumor therapy.
AB  - We previously showed a significant enhancement of tirapazamine-induced
      cytotoxicity and DNA damage after binding with copper. This result suggests that
      conjugates of tirapazamine with radioactive copper, i.e., 64Cu and 67Cu, may
      offer potential for targeted therapy of a wide range of advanced stage tumors
      including a possible treatment for patients with solitary hepatocellular
      carcinoma by intrahepatic arterial infusion. Major supporting considerations
      include: (a) tirapazamine having a high selective toxicity against hypoxic cells;
      (b) the nature of radioactive decay of these copper isotopes and obtainable high
      specific activity; and (c) simple procedure for the production of copper
      tirapazamine complex.

PMID- 9544683
TI  - Health hazards of radiation exposure in the context of brain imaging research:
      special consideration for children.
AB  - This review provides information on health and biological effects of low-dose
      radiation to help institutional review boards and investigators make educated
      assessments of the risks of low-level radiation exposure involved in research,
      particularly in children. METHODS: Studies of low-level radiation exposure with
      large sample sizes and long follow-up were reviewed. To help interpret the
      studies, we clarified the measures and measurement strategies of radiation
      exposure and of health risks. The few large studies of risks of low-level
      radiation in children have failed to detect an increased incidence of cancer.
      Most studies of low-level radiation involve adults. RESULTS: The risk of
      increased rates of cancer after low-level radiation exposure is not supported by
      population studies of health hazards from exposure to background radiation, radon
      in homes, radiation in the workplace or radiotherapy. Compared to the frequency
      of daily spontaneous genetic mutations, the biological effect of low-level
      radiation at the cellular level seems extremely low. Furthermore, the
      potentiation of cellular repair mechanisms by low-level radiation may result in a
      protective effect from subsequent high-level radiation. Studies approved by
      institutional review boards in the U.S. that involve the exposure of healthy
      normal children to ionizing radiation were reviewed. CONCLUSION: Health risks
      from low-level radiation could not be detected above the "noise" of adverse
      events of everyday life. In addition, no data were found that demonstrated higher
      risks with younger age at low-level radiation exposure.

PMID- 9544682
TI  - Current concepts on the diagnostic use of MIBG in children.
AB  - Metaiodobenzylguanidine (MIBG) was developed 18 yr ago for scintigraphic imaging
      of the adrenomedullary tumors pheochromocytoma and neuroblastoma. Many studies
      have shown the usefulness of this agent for the management of patients with
      neuroblastoma or pheochromocytoma, and the 131I-labeled form was recently
      approved by the Food and Drug Administration for use in the U.S. This article
      summarizes our current concepts on the diagnostic use of MIBG in children. The
      radioisotopes available for labeling of MIBG and related compounds, the
      dosimetry, metabolism and mechanisms of uptake and retention are discussed. Our
      protocols for imaging both 131I-MIBG and 123I-MIBG, along with the normal
      distribution of these compounds, are reviewed. The use of MIBG for the management
      of neuroblastoma, and comparisons with other radiotracers available for imaging
      neuroblastomas are also addressed.

PMID- 9544684
TI  - Kinetic studies with iodine-123-labeled serum amyloid P component in patients
      with systemic AA and AL amyloidosis and assessment of clinical value.
AB  - In systemic amyloidosis, widespread amyloid deposition interferes with organ
      function, frequently with fatal consequences. Diagnosis rests on demonstrating
      amyloid deposits in the tissues, traditionally with histology although
      scintigraphic imaging with radiolabeled serum amyloid P component (SAP) has
      lately been developed as a specific noninvasive alternative. We report a detailed
      analysis of the abnormal turnover of SAP in patients with systemic amyloidosis
      and an assessment of its clinical value. METHODS: Iodine-123-labeled human SAP
      (200 MBq) SAP was injected intravenously into 49 patients with histologically
      proven systemic AA- or AL- amyloidosis and in 7 control subjects. Plasma
      clearance and whole-body retention of labeled SAP were analyzed over 48 hr using
      plasma sampling, whole-body gamma camera imaging and measurement of radioactivity
      in the urine. The rate of SAP synthesis and interstitial exchange were
      determined, and the size of the amyloid compartment was compared with clinical
      estimates of whole-body amyloid load and patient survival. RESULTS: All plasma
      time-activity curves were biphasic. In comparison with control subjects, patients
      with amyloidosis showed significantly faster plasma disappearance [4-hr value: AA
      48% +/- 18%, AL 45% +/- 15% versus 65% +/- 8% (p < 0.05)], higher total-body
      retention 48 hr p.i. [AA 74% +/- 14%, AL 73% +/- 17% versus 46% +/- 15% (p <
      0.01)] and especially higher extravascular retention 48 hr p.i. [AA 59% +/- 16%,
      AL 58% +/- 19% versus 30% +/- 14% (p < 0.01)]. Extravascular retention correlated
      with clinical estimation of the amyloid load. If extravascular retention values
      in patients with AL amyloidosis were over 60%, survival was decreased (median 4
      versus 23 mo, p < 0.001). Markedly increased interstitial exchange rates were
      present in amyloidosis (AA 64 +/- 61, AL 50 +/- 37 versus 18 +/- 8 mg/hr),
      whereas the SAP synthesis rate did not differ from the control values (AA 5.0 +/-
      3.0, AL 5.5 +/- 3.2 versus 4.5 +/- 1.4 mg/hr). CONCLUSION: The presence of
      systemic amyloidosis is characterized by accelerated initial clearance of 123I
      SAP from the plasma and increased interstitial exchange rate and extravascular
      retention. These findings reflect reversible binding of radiolabeled SAP to
      amyloid deposits and provide clinically useful information for diagnosis,
      monitoring of therapy and prognosis in patients with systemic amyloidosis.

PMID- 9544685
TI  - Diagnostic evaluation of the adrenal incidentaloma: decision and cost
      effectiveness analyses.
AB  - The goal of this study was to examine the clinical and economic outcomes of
      alternative diagnostic strategies for differentiating benign from malignant
      adrenal masses. METHODS: We used cost-effectiveness assessment derived from
      decision analysis and the economic perspective of the payer of health care
      services. One-time evaluation with fine-needle aspiration (FNA) and combinations
      of chemical-shift MRI, noncontrast CT, 131I-6beta-iodomethylnorcholesterol (NP
      59) scintigraphy, with or without FNA, in a hypothetical cohort of 1000 patients
      with incidentally discovered unilateral, nonhypersecretory adrenal masses. We
      calculated and compared the diagnostic effectiveness, costs and cost
      effectiveness of the alternative strategies based on estimates from published
      literature and institutional charge data. RESULTS: At an assumed baseline
      malignancy rate of 0.25, diagnostic utility varied from 0.31 (CT0) to 0.965 (NP
      59) and diagnostic accuracy from 0.655 [noncontrast CT using a cut-off
      attenuation value of > or = 0 (CT0)] to 0.983 (NP-59). The average cost per
      patient per strategy ranged from $746 (NP-59) to $1745 (MRI +/- FNA). The best
      and worst potential cost-to-diagnostic utility ratios were 773 (NP-59) and 2839
      (CT0) and 759 (NP-59) and 1982 (MRI +/- FNA) for cost and diagnostic accuracy,
      respectively. The NP-59 strategy was the optimal choice regardless of the
      expected outcome examined: cost, diagnostic utility, diagnostic accuracy or cost
      effectiveness. Varying the prevalence of malignancy did not alter the cost
      effectiveness advantage of NP-59 over the other diagnostic modalities.
      CONCLUSION: Based on available estimates of reimbursement costs and diagnostic
      test performance and using reasonable clinical assumptions, our results indicate
      that the NP-59 strategy is the most cost-effective diagnostic tool for evaluating
      adrenal incidentalomas over a wide range of malignancy rates and that additional
      clinical studies are warranted to confirm this cost-effectiveness advantage.

PMID- 9544686
TI  - Radioiodine treatment outcomes in thyroid glands previously irradiated for
      Graves' hyperthyroidism.
AB  - Persistent or recurrent Graves' hyperthyroidism after an initial treatment dose
      of radioactive iodine (RAI) is not uncommon and usually necessitates additional
      administrations. The radiation sensitivity of the previously irradiated thyroid
      gland is unknown but is of importance in selecting the retreatment dose. METHODS:
      A retrospective analysis of patients receiving RAI for Graves' hyperthyroidism
      was undertaken. A first treatment dose was given to 1076 patients, and 168 of
      these patients subsequently required a second dose for persistent or recurrent
      hyperthyroidism (interval between RAI treatments, 8.5 +/- 17.1 mo). RESULTS:
      Paired comparisons for retreated patients showed similar RAI doses (291 +/- 95
      MBq and 283 +/- 129 MBq; p = ns) and treatment intensities (3.26 +/- 1.87 MBq g(
      1) and 3.48 +/- 1.88 MBq g(-1); p = ns) for first and second treatments.
      Hypothyroidism occurred significantly earlier and more frequently after the first
      RAI dose (p = 0.002), but there was no difference for persistent or recurrent
      hyperthyroid events (p = 0.14). Multivariate regression established that the RAI
      treatment number (first or second) was a significant independent determinant of
      hypothyroid (p = 0.008) and combined (p = 0.001) events, whereas RAI dose and
      dose intensity were not. CONCLUSION: We conclude that previous RAI treatment
      failure does not lessen the chance of successfully eradicating Graves'
      hyperthyroidism with additional RAI treatment. Furthermore, the previously
      irradiated thyroid gland may be less susceptible to early hypothyroidism than the
      RAI-naive thyroid gland.

PMID- 9544687
TI  - Prediction of prognosis in peripheral facial nerve paralysis using submandibular
      gland scintigraphy.
AB  - In this study, we evaluated the ability of submandibular gland scintigraphy to
      predict the prognosis of peripheral facial nerve paralysis. METHODS:
      Submandibular gland scintigraphy was performed in 78 patients with acute
      peripheral facial nerve paralysis. After injection of 180-370 MBq
      [99mTc]pertechnetate, serial 1-min images were acquired for 25 min. At 15 min
      after injection of radionuclide, ascorbic acid was administered intraorally to
      stimulate salivary secretion. Regions of interest were set manually on both
      submandibular glands, and time-activity curves were generated. The ratios of peak
      count density (PCR) and washout (WR) of the affected side to the normal side were
      calculated. Parameters of > or = 0.8 suggested normal affected submandibular
      function and indicated a good prognosis. RESULTS: Complete recovery of facial
      nerve paralysis was observed in 52 of 78 patients. The sensitivity, specificity
      and accuracy of PCR for a good prognosis were 79%, 50% and 69%, and those of WR
      were 85%, 77% and 82%, respectively. Positive and negative predictive values for
      a good prognosis were 76% and 54% in PCR and 88% and 71% in WR, respectively.
      When WR obtained within 14 days of the onset was used, positive and negative
      predictive values for a good prognosis were 94% and 73%, respectively. None of
      the eight patients who had values of <0.8 for both parameters within 14 days of
      the onset recovered completely. CONCLUSION: Submandibular gland scintigraphy can
      serve as a reliable indicator to predict the prognosis of acute peripheral facial
      nerve paralysis in its early symptomatic period.

PMID- 9544688
TI  - Pulmonary SPECT imaging and the stripe sign.
AB  - A patient with high clinical suspicion for pulmonary embolism underwent a
      diagnostic scintigraphic ventilation/perfusion scan. The planar images revealed
      an unmatched perfusion defect with a stripe sign in the right middle lobe. A
      stripe sign is the appearance of normally perfused tissue between the defect and
      the pleural surface suggesting a nonpleural-based abnormality. SPECT images
      acquired in the same study period, however, failed to demonstrate normally
      perfused tissue between the defect and the pleural surface. Previous studies have
      compared planar ventilation/perfusion studies with stripe sign perfusion defects
      to pulmonary angiography. The results suggest that stripe sign perfusion defects
      are generally not due to emboli. However, planar imaging is projectional and may
      miss pleural contact in some perfusion lesions depending on the projection. In
      the absence of SPECT data, the significance of the stripe sign may need to be
      reassessed.

PMID- 9544689
TI  - Early detection of bleomycin-induced lung injury in rat using indium-111-labeled
      antibody directed against intercellular adhesion molecule-1.
AB  - We have investigated whether an (111)In-labeled mouse monoclonal antibody to rat
      intercellular adhesion molecule-1 ((111)In*aICAM-1) could detect lung injury
      early in rats treated with bleomycin. METHODS: Rats received an intravenous
      injection of either (111)In*aICAM-1 or (111)In-labeled normal mouse IgG
      ((111)In*nmIgG) and were imaged and killed 24 hr later. Lung injury was induced
      by an intratracheal injection of bleomycin 4 or 24 hr before the rats were
      killed. After death, tissue was removed and activity was measured, lungs were
      cryostat-sectioned to detect the presence of ICAM-1 by immunofluorescence, and
      the up-regulation of LFA-1alpha was examined on blood polymorphonuclear
      leukocytes (PMNs) using fluorescence-activated cell-sorter (FACS) analysis.
      RESULTS: In rats injected with (111)In*aICAM-1, the percent injected dose/organ
      in lungs both at 4 and 24 hr postbleomycin increased significantly compared to
      the values in either uninjured rats or rats that received (111)In*nmIgG. At 4 and
      24 hr postinjury, the target-to-blood (T/B) ratio was 8/1 and 6/1, respectively.
      For (111)In*nmIgG, the T/B ratio at 4 hr was 0.5/1 and 0.4/1 at 24 hr. In
      (111)In*aICAM-1 rats injured at 4 or 24 hr, images could easily be distinguished
      from uninjured rats. All images of (111)In*nmIgG rats showed only cardiac blood
      pool and liver activity with little lung activity. Lung ICAM-1 immunofluorescence
      intensity increased in the bleomycin-treated samples compared to uninjured lungs.
      Expression of LFA-1alpha on PMNs increased 19% and 210% at 4 hr and 24 hr
      postinjury, respectively, compared to control values. CONCLUSION: Biodistribution
      and imaging data demonstrate that (111)In*aICAM-1 can detect early acute
      bleomycin-induced lung injury. Immunofluorescence and FACS data suggest that
      (111)In*ICAM-1 uptake is a specific process. This antibody has potential as an
      early radionuclide detector of acute inflammations.

PMID- 9544690
TI  - Noninvasive methods for quantitating blood time-activity curves from mouse PET
      images obtained with fluorine-18-fluorodeoxyglucose.
AB  - The mouse model is currently being explored for various applications with PET
      imaging. Low resolution of current animal scanners relative to mouse size leads
      to difficulty in quantitating data from mouse PET images. We have, therefore,
      investigated methods for determining blood time-activity curves (TACs) from mouse
      PET studies done with fluorine-18-fluorodeoxyglucose (FDG). METHODS: Eight mice
      were fasted, the tail vein was injected with 150-300 microCi of FDG and dynamic
      images were acquired with a CTI/Siemens (Knoxville, TN) animal tomograph for 64.5
      min. Concurrently, 11-14 left ventricle (LV) blood samples were drawn directly
      from the LV chamber. Organ TACs were obtained by drawing circular regions of
      interest (ROIs) of various sizes on images of the heart, liver and brain. For
      each mouse, the FDG model parameter K = (K1 x k3)/(k2 + k3) was estimated by a
      Patlak algorithm with various estimates of the blood TAC and, as a reference
      tissue TAC, the brain TAC. RESULTS: Most partial-volume-corrected heart ROI TACs
      overestimated the LV samples. Blood TACs from heart images produced statistically
      different estimates of K than did the LV samples. The liver image-derived blood
      TACs yielded estimates of K that were comparable to those yielded by the LV
      samples. Estimates of K determined with two directly sampled LV points in
      conjunction with the liver image-derived TAC were not statistically different
      from the estimates obtained with the LV samples. The size and location of ROIs on
      images of the liver minimally affected the TACs. CONCLUSION: We have shown that
      it is experimentally possible to obtain a blood TAC from mouse studies by
      repeatedly sampling from the LV. We have also shown that images of the liver can
      be used to reliably estimate the blood TAC. Future FDG PET studies with the mouse
      model will benefit from this demonstrated ability to noninvasively quantitate
      blood TACs directly from FDG PET images.

PMID- 9544691
TI  - Artificial neural network as a tool to compensate for scatter and attenuation in
      radionuclide imaging.
AB  - This study investigates the ability of artificial neural networks (ANN) to
      simultaneously correct for attenuation and Compton scattering in scintigraphic
      imaging. METHODS: Three sets of experiments are conducted using images of
      radioactive sources with various shapes and distributions in a homogeneous
      medium. Numerical Monte Carlo simulations and physical phantom acquisitions of
      radioactive geometric sources provide the basic material for correction. Our
      method is based on the following assumptions: information needed to correct for
      scattering can be extracted from the energy spectrum at each pixel without any
      assumption concerning the source distribution, and two diametrically opposed
      energy spectrum acquisitions yield enough information on the source location in
      the diffusing medium for simultaneous correction for attenuation and scattering.
      RESULTS: Qualitative and quantitative evaluations of scatter correction by ANN
      demonstrate its ability to perform scatter correction from the energy spectra
      observed in each pixel. By using the energy spectra of incident photons detected
      in two diametrically opposed images, multilayer neural networks are able to
      perform a proper restitution of projection images without any assumption on
      geometry or position of radioactive sources in simple geometric cases. ANN
      corrections compare favorably to those provided by five of the most popular
      methods. A satisfying correction of both scatter and attenuation is observed for
      a human pelvis scan obtained during routine clinical practice. CONCLUSION: An ANN
      is an efficient tool for attenuation and Compton scattering in simple model
      cases. The results obtained for routine scintigrams in a much more complex
      situation are strong incentives for performing further studies.

PMID- 9544692
TI  - Supercomputer description of human lung morphology for imaging analysis.
AB  - A supercomputer code that describes the three-dimensional branching structure of
      the human lung has been developed. The algorithm was written for the Cray C94. In
      our simulations, the human lung was divided into a matrix containing discrete
      volumes (voxels) so as to be compatible with analyses of SPECT images. The matrix
      has 3840 voxels. The matrix can be segmented into transverse, sagittal and
      coronal layers analogous to human subject examinations. The compositions of
      individual voxels were identified by the type and respective number of airways
      present. The code provides a mapping of the spatial positions of the almost 17
      million airways in human lungs and unambiguously assigns each airway to a voxel.
      Thus, the clinician and research scientist in the medical arena have a powerful
      new tool to be used in imaging analyses. The code was designed to be integrated
      into diverse applications, including the interpretation of SPECT images, the
      design of inhalation exposure experiments and the targeted delivery of inhaled
      pharmacologic drugs.

PMID- 9544693
TI  - Inducible interleukin 4 (IL-4) production and mRNA expression following exposure
      of mice to chemical allergens.
AB  - Previous investigations have indicated that different classes of chemical
      allergen provoke discrete immune responses in mice characterized by the
      development of selective cytokine secretion patterns by draining lymph node
      cells. It was found that, in mice exposed chronically to chemical respiratory
      allergens, lymph node cells produced high levels of mitogen-inducible interleukin
      4 (IL-4), a cytokine necessary for the development of IgE antibody responses. In
      contrast, exposure of mice to contact allergens resulted in only low levels of IL
      4 production. The studies described here were conducted to determine whether
      differentially induced expression of IL-4 messenger RNA was independent of the
      need for mitogen stimulation, unlike secretion of IL-4 protein. Mice were exposed
      to concentrations of trimellitic anhydride (TMA), a respiratory allergen, or to
      2,4-dinitrochlorobenzene (DNCB), a contact allergen, under conditions of
      equivalent immunogenicity and where the former, but not the latter, resulted in
      significant production of mitogen-inducible IL-4 protein. The steady state levels
      of IL-4 mRNA in draining lymph nodes were measured by reverse transcription
      polymerase chain reaction after a single or repeated daily application of the
      test chemical to the ears of chronically sensitized mice. Expression of mRNA for
      IL-4 was evaluated relative to the expression of a housekeeping gene,
      glyceraldehyde 3-phosphate dehydrogenase. Both chemicals elicited increased
      steady state levels of IL-4 mRNA by draining lymph node cells compared with
      vehicle-treated and naive controls. However, using two different treatment
      protocols, a chronic and an abbreviated chronic protocol and at all times
      examined, the elevation in IL-4 mRNA steady state levels induced by TMA was
      greater than that observed with DNCB. These data provide further support for the
      differential stimulation by contact and respiratory chemical allergens of
      cytokine secretion patterns in mice and demonstrate that the divergent production
      of IL-4 in response to these classes of allergen is at least partly
      transcriptionally regulated.

PMID- 9544695
TI  - Hepatotoxicity of the drinking water disinfection by-product, dichloroacetic
      acid, in the medaka small fish model.
AB  - Recent studies have shown that dichloroacetic acid (DCA), a by-product of
      chlorination of public water supplies, is carcinogenic to both rats and mice.
      However, conflicting data have left the mechanism of DCA carcinogenicity, vital
      to assessment of human health risk, unclear. Elucidation of this mechanism in
      another animal model at a different phyletic level than rodents would advance the
      risk assessment process for government agencies concerned with regulation and
      provision of safe drinking water. The Japanese medaka (Oryzias latipes), a well
      characterized small fish model, is being used increasingly for carcinogenicity
      testing because of its low cost, ease of maintenance and carcinogen sensitivity.
      In this study, 6-week-old medaka were exposed to diethylnitrosamine (DEN, a known
      initiator), followed by continuous exposure to 0.5 or 2.0 g/l DCA in the ambient
      water, over a 4 week period. At both exposure concentrations, changes in the
      liver included marked hepatocellular cytoplasmic vacuolation, cytomegaly,
      karyomegaly, nuclear atypia and multifocal areas of hepatocellular necrosis and
      loss as early as week two of DCA exposure. The majority of the hepatocellular
      cytoplasmic vacuoles were shown by periodic acid Schiff (PAS) staining to contain
      large amounts of glycogen. These elevated glycogen levels may reflect a
      disruption in the enzyme pathways for glycolysis. The total cellular changes seen
      in this short-term exposure regimen are compatible with preneoplastic changes
      seen in rats and mice exposed to DCA. The results of this study strengthen the
      role of the Japanese medaka as a suitable species in carcinogenicity testing as
      well as its implementation in the risk assessment process for DCA across several
      phyletic levels.

PMID- 9544694
TI  - Effects of 2-amino-7-phosphonohepatanoic acid, melatonin or NG-nitro-L-arginine
      on cyanide or N-methyl-D-aspartate-induced neurotoxicity in rat cortical cells.
AB  - When cortical neuronal cells were exposed to potassium cyanide (0.01, 0.05, 0.1,
      0.5, or 1.0 mM) or N-methyl-D-aspartate (NMDA: 0.005, 0.01, 0.05, 0.1, or 0.2 mM)
      for 24 h at 37 degrees C in a 95% air and 5% CO2 environment, lactate
      dehydrogenase (LDH) efflux into the extracellular fluid from the cortical cells
      was significantly increased in a concentration dependent manner and morphological
      changes were observed. The increased LDH efflux and the morphological changes in
      cortical cells induced by potassium cyanide or NMDA were blocked by co-exposure
      to 2-amino-7-phosphonoheptanoic acid (AP7: 1.0 mM), a selective antagonist of the
      NMDA receptor, melatonin (1.0 mM), a potent hydroxyl and peroxyl radical
      scavenger, or NG-nitro-L-arginine (1.0 mM), an inhibitor of nitric oxide (NO)
      synthase. These results suggest that activation of NMDA receptor and NO synthase
      and/or free radical formation may contribute to the development of neurotoxicity
      induced by cyanide or NMDA.

PMID- 9544696
TI  - The effect of heptachlor, a chlorinated hydrocarbon insecticide, on p53 tumor
      suppressor in human lymphocytes.
AB  - Previous studies have shown that heptachlor, a chlorinated hydrocarbon
      insecticide, is a liver tumor promoter in rats and mice and induces tumor
      promoting-like alterations in human myeloblastic leukemia cells. The nature of
      tumor promotion is multifaceted and has recently been shown to include
      suppression of programmed cell death (apoptosis) as a mechanism by which a tumor
      promoter can prolong cell viability. The ability of tumor promoters to suppress
      apoptosis prompted us to address the question of whether heptachlor is capable of
      effecting the expression of genes involved in lymphocyte apoptosis, in
      particular, the p53 tumor suppressor gene. Experiments with a CEM x 174 cell
      line, a hybrid of human T and B cells, revealed that heptachlor downregulated p53
      gene expression at the post-transcriptional level without changing levels of mRNA
      in the cells. The heptachlor-induced reduction in the basal levels of expression
      of this gene was both in a concentration and time-dependent manner.

PMID- 9544697
TI  - Momordica charantia (Bitter Gourd) peel, pulp, seed and whole fruit extract
      inhibits mouse skin papillomagenesis.
AB  - The present study was designed to elucidate the inhibitory potential of Momordica
      charantia (Bitter Gourd) peel, pulp, seed and whole fruit extract on mouse skin
      papillomagensis with the modulatory influence of biotransformation system
      enzymes. Topical application of Momordica whole fruit extract (100 microl/animal
      per day) during the peri-initiation stage (1 week before and 2 weeks after
      initiation) by 7,12-dimethylbenz[a]anthracene (DMBA) and/or during the tumor
      promotion stage reduced the (i) tumor burden to 4.26, 3.72 and 3.11 (positive
      control value: 5.42); (ii) cumulative number of papillomas to 81, 67 and 53
      (positive control value: 103); and (iii) percent incidence of mice bearing
      papillomas to 100, 94 and 94, respectively (positive control value: 100). In a
      comparison of the anticarcinogenic efficacy of Momordica peel, pulp, seed and
      whole fruit extract (100 microl/animal per day), after topical treatment during
      the peri-initiation and during the tumor promotion stage, revealed the modulation
      of the (i) tumor burden (tumors/mouse) to 3.06, 3.61, 3.17 and 3.11; (ii)
      cumulative number of papillomas to 49, 65, 54 and 53; and (iii) percent incidence
      of mice bearing papillomas to 84, 100, 94 and 94, respectively. Significant
      elevation in the sulfhydryl (-SH) level was observed in the liver and skin
      tissues by the topical treatment of Momordica peel, pulp, seed and whole fruit
      extract. Elevation in the hepatic levels of cytosolic glutathione S-transferase
      (GST) and microsomal cytochrome b, was also observed by the topical treatment of
      Momordica peel, seed and whole fruit extract. The results suggest the maximum
      chemopreventive potential is in the Momordica peel. Equivocal efficacy is in the
      Momordica seed and whole fruit extract. Biotransformation system enzymes may be
      the cause of this reduced papillomagenesis.

PMID- 9544698
TI  - Effect of chronic poisoning with aluminum on the renal handling of phosphate in
      the rat.
AB  - The effects of aluminum on renal function and phosphate handling were studied
      using clearance techniques in chronically-intoxicated rats. Rats were given
      aluminum hydroxide (80 mg/kg b.w., i.p.), three times per week during 6 months.
      The phosphate tubular transport capacity was evaluated by determining the maximum
      tubular transport (TmRPi) and the fractional excretion of phosphate (FE% Pi)
      during the infusion of phosphate solutions with increasing concentrations (0, 9,
      18, 33 mM). Parathyroid gland function was studied using indirect methods:
      calcemia recovery after EDTA administration and the nephrogenic excretion of cAMP
      as indicative of renal PTH actions, by RIA. The systemic acid base status was
      determined and food intake and rat growth were controlled in both groups. No
      changes were observed in the renal function. Pi reabsorption values per ml
      glomerular filtration rate (TRPi/GFR microg/ml) for different Pi plasmatic
      concentrations were distributed following a saturation curve compatible with a
      saturation kinetics. Aluminum increased TmRPi/GFR in treated animals (T) 76+/-4
      as compared with control animals (C) 57+/-7 microg/ml, without a statistical
      modification in the apparent affinity. The FE% Pi and FE% Na were significantly
      lower in treated animals than in control animals. There were neither systemic
      variations in the acid-base balance nor in the Ca and Pi concentrations in
      plasma. The calcemia recovery following a hypocalcemic stimulus and the
      nephrogenic excretion of cAMP (T: 44+/-4; C: 91+/-7 pmol/min) were diminished.
      Considering all these facts, it can be postulated that the aluminum renal effect
      is associated from a decrease in PTH phosphaturic capacity. Nevertheless, other
      associated factors like minor phosphate intestinal absorption rate may not be
      disregarded, even though there were no significant intake variations.

PMID- 9544700
TI  - The acetaminophen regioisomer 3'-hydroxyacetanilide inhibits and covalently binds
      to cytochrome P450 2E1.
AB  - 3'-Hydroxyacetanilide has been previously studied as a nontoxic regioisomer of
      the analgesic acetaminophen (4'-hydroxyacetanilide). The radiolabeled derivative
      has been shown to covalently bind to liver proteins at levels similar to that
      observed with hepatotoxic doses of radiolabeled acetaminophen with no evidence of
      hepatic damage. Using an anti-arylacetamide antiserum the primary protein adduct
      detected following administration of 3'-hydroxyacetanilide (300 and 600 mg/kg) to
      mice was a 50 kDa microsomal protein that co-migrated with cytochrome P450 2E1.
      Cytochrome P450 2E1 enzyme activity (p-nitrophenol hydroxylase) was decreased by
      79% in the mice treated with 3'-hydroxyacetanilide (600 mg/kg). Incubation of 3'
      hydroxyacetanilide with hepatic microsomes resulted in a time dependent 47%
      decrease in cytochrome P450 2E1 activity. Pre-incubation of acetaminophen with
      microsomes did not result in covalent binding to the cytochrome P450 nor was
      there a decrease in p-nitrophenol hydroxylase activity. These data suggest that
      3'-hydroxyacetanilide covalently binds to cytochrome P450 2E1 with preferential
      loss of activity.

PMID- 9544699
TI  - Induction of heme oxygenase-1 in toxic renal injury: mercuric chloride-induced
      acute renal failure in rat.
AB  - It is known that mercuric chloride (HgCl2) is a nephrotoxicant. When HgCl2 (1
      mg/kg body weight) was intraperitoneally injected into rats, acute renal failure
      was induced. Histological changes in the kidneys were exclusively observed in the
      proximal tubules and the severe necrosis was found as early as 24 h after HgCl2
      injection. The heme oxygenase-1 (HO-1) mRNA was strongly and promptly induced at
      about 2.5 h, the earliest time examined and abruptly decreased after the
      injection. Whereas the time course of HO-1 protein level was delayed as compared
      with that of HO-1 mRNA level. The levels of HO-1 mRNA and protein similarly
      increased with dose-dependent manner. The localization of HO-1 protein was
      restricted to the tubule cells. These findings suggest the potential involvement
      of HO-1 induction in the response to HgCl2-induced acute renal injury.

PMID- 9544701
TI  - Regions of the Escherichia coli primary sigma factor sigma70 that are involved in
      interaction with RNA polymerase core enzyme.
AB  - BACKGROUND: The sigma factors of bacterial RNA polymerase are required for
      recognition of promoters in transcription initiation. Most sigma factors share
      several regions with significant homology in their amino acid sequences (regions
      1-4). Some primary sigma factors carry a large nonconserved segment between
      regions 1 and 2. The binding of an sigma factor to the core enzyme alters the
      structure and properties of the sigma factor, but little is known about the
      binding mechanism and subsequent reactions. In this report, we employed the
      protein footprinting method to investigate the alteration of the structure and
      function of Escherichia coli sigma70 by binding to core enzyme and promoter DNA.
      RESULTS: A segment between regions 1.1 and 1.2, and that in region 3.2, were
      preferentially cleaved by hydroxyl radicals. Upon binding to the core enzyme,
      segments in regions 1.1, 2, 3 and 4 were substantially protected, while cleavage
      at a small segment in region 4.2 was weakly enhanced. In a binary complex of
      holoenzyme and promoter DNA, additional segments in regions 2.4 and 4.2 were
      protected, while the protection at region 1.1 disappeared. The nonconserved
      acidic region of sigma70 in the holoenzyme became hypersensitive upon binding to
      DNA. CONCLUSIONS: These results suggest that not only the conserved region 2, but
      also regions 1.1, 3 and 4 of the sigma factor are involved in binding to the core
      enzyme. The nonconserved acidic region is likely to be more exposed by further
      binding of sigma factor to promoter DNA.

PMID- 9544702
TI  - Roles of TraI protein with activities of cleaving and rejoining the single
      stranded DNA in both initiation and termination of conjugal DNA transfer.
AB  - BACKGROUND: The plasmid R100 encodes the TraI protein, which is required for
      conjugal DNA transfer. TraI has the activity of site- and strand-specific nicking
      of the supercoiled plasmid DNA. The molecular mechanism of this specific nicking,
      which is supposed to be the initiation reaction of DNA transfer, is not
      understood. RESULTS: We have demonstrated that TraI has the ability to cleave the
      single-stranded DNA at the same site as the nicking site (nic) in a region, which
      we here refer to as sbi. The product contained the TraI protein which was
      covalently linked to the newly generated 5' end of the nicking reaction. Both the
      cleaving and nicking reactions took place under almost the same conditions and
      required the presence of the sbi region. DNase I-footprinting analysis revealed
      that the TraI bound to the single-stranded DNA of the sbi region. TraI did not
      cleave the double-stranded DNA fragment, but it did cleave the double-stranded
      DNA with a single-stranded DNA portion in the sbi region. KMnO4 mapping analysis
      revealed that TraI can melt the sbi region in the supercoiled DNA to generate a
      single-stranded portion. We have also demonstrated that TraI was able to rejoin
      the cleaved products. The rejoining reaction required the 5' end of one cleaved
      product with the TraI covalently attached and the 3' end of the other product
      containing the sbi region. CONCLUSIONS: Our results demonstrate that the nicking
      reaction-the initiation reaction of DNA transfer-is actually the cleaving
      reaction of the single-stranded DNA. TraI, which has both cleaving and rejoining
      activities, is thought to be involved in the termination of DNA transfer, to give
      a copy of the conjugative plasmid by joining the 5' end, which is generated by
      the initiation reaction, with the 3' end, which will be generated upon cleavage
      of the sbi region appearing after one round of the rolling circle replication of
      the plasmid.

PMID- 9544703
TI  - Gin4 of S. cerevisiae is a bud neck protein that interacts with the Cdc28
      complex.
AB  - BACKGROUND: A number of proteins make up the Cdc28 complex in Saccharomyces
      cerevisiae, and regulate CDK activity. The cell cycle regulator Nik1 (Hsl1) is a
      protein kinase that interacts with the Cdc28 complex. The growth inhibitor Gin4
      is structurally similar to Nik1 and may play a redundant role in the regulation
      of the cell cycle. We investigated the functions of Gin4 with respect to those of
      Nik1. RESULTS: GIN4 was not essential for growth, and cells deficient in the GIN4
      gene displayed no obvious defects in cell cycle regulation. The delta(gin)4
      delta(nik)1 strain was temperature sensitive and showed an abnormal cell shape
      and FACS profile at permissive temperatures. GFP-fused Gin4 was localized at the
      bud-neck from late G1 to the M phase. Over-production of the C-terminal portion
      of Gin4 was toxic for cell growth, and this domain was required for the bud-neck
      localization of Gin4-GFP. High copy expression of Gin4-GFP disturbed the bud-neck
      localization of Gin4 in the abnormally elongated cells. Cytokinesis was defective
      in the delta(gin)4 cdc28 double mutants. The GST-Gin4 fusion protein physically
      associates with the Cdc28 complex. CONCLUSIONS: Gin4 is a bud-neck protein. GIN4
      and NIK1 have distinct but partially overlapping functions. The major function of
      GIN4 is to ensure proper mitotic progression and cytokinesis.

PMID- 9544704
TI  - Two mechanisms in the action of repressor deltaEF1: binding site competition with
      an activator and active repression.
AB  - BACKGROUND: Counteraction between activators and repressors is crucial for the
      regulation of a number of cell-specific enhancers, where an activator and a
      repressor are mutually competitive in binding to the same site. DeltaEF1 is a
      repressor protein of delta1-crystallin minimal enhancer DC5 binding at the CACCT
      site, and inhibits activator deltaEF3 from binding to the overlapped site. It has
      two zinc finger clusters N-fin and C-fin, close to N- and C-termini,
      respectively, and a homeodomain in the middle. deltaEF1 also binds to the E2-box
      sequence CACCTG, and represses E2-box-dependent enhancers. RESULTS: The mechanism
      of the repressor action of deltaEF1 was investigated by examining various
      deletion mutants of deltaEF1 for their activity to repress delta1-crystallin
      enhancer fragment HN which contained DC5 sequence and an additional activator
      site. Both zinc finger clusters were found to be essential for DNA binding and
      repression, but the homeodomain was not. In addition, the NR domain close to the
      N-terminus was required for full repression. The NR domain showed active
      repression when fused to the Gal4 DNA binding domain. Active repression by
      deltaEF1, dependent on the NR domain, was also demonstrated in a situation where
      the binding sites of deltaEF1 and deltaEF3 were separated. N-fin and C-fin in
      their isolated forms bind the 5'-(T/C)ACCTG-3' and 5'-(t/C)ACCT-3' sequences,
      respectively, while the homeodomain showed no DNA binding activity. An analysis
      of DNA binding of the delta(Int)F form, having both N-fin and C-fin, indicated
      that a single DNA binding domain is assembled from two zinc finger clusters.
      CONCLUSION: Two mechanisms are involved in the repressor action of deltaEF1.
      First, a binding site competition with an activator which depends on the
      integrity of both zinc finger clusters, and second, an active repression to
      silence an enhancer which is attributed to the NR domain.

PMID- 9544705
TI  - Double-cleavage production of the CTL epitope by proteasomes and PA28: role of
      the flanking region.
AB  - BACKGROUND: Proteasomes are known to produce major histocompatibility complex
      (MHC) class I ligands from endogenous antigens, and the gamma-interferon
      inducible proteasome activator PA28 has been thought to play an important role in
      the generation of immunodominant MHC ligands by proteasomes. Several attempts
      have been made to show that proteasomes have the ability to yield cytotoxic T
      lymphocyte (CTL) epitopes effectively from model polypeptides derived from viral
      and intracellular proteins in vitro, but their antigen processing mechanism is
      poorly understood. RESULTS: Proteasomes produce the tumour rejection antigen
      precursor peptide pRL1b (SIIPGLPLSL), but not pRL1a (IPGLPLSL), bound to the H
      2Ld molecule, from synthetic peptides covering the CTL epitope. This double
      cleavage production of pRL1b by proteasomes seemed to depend on the length of the
      flanking regions adjacent to either end of the CTL epitope, in which their
      successive deletions caused the almost complete prevention of pRL1b excision. The
      newly identified PA28 collaborates with proteasomes for efficient production of
      pRL1b, by promoting not only single cleavage of all susceptible peptides, but
      also dual cleavage in some peptides harboring certain characteristic lengths.
      CONCLUSION: The flanking regions outside pRL1b of suitable length appear to be
      essential for the correct CTL epitope production, possibly functioning as anchors
      to trap target peptides for proteasomal degradation. We propose a novel mechanism
      for dual-cleavage excision of immunodominant epitopes by proteasomes and PA28.

PMID- 9544706
TI  - Induction of labor with intravaginal administration of misoprostol.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of
      intravaginal misoprostol for labor induction. METHODS: 110 singleton term
      pregnancies with or without rupture of membranes were enrolled. Fractionated
      doses of misoprostol were applied (50-100 microg), every 6 h until a maximum of
      three doses or beginning of labor. RESULTS: The average interval (+/- S.D.) from
      vaginal application to the beginning of active labor and to delivery were,
      respectively, 9.5 +/- 5.7 h and 14.8 +/- 9.5 h. Failed labor induction was
      observed in two cases (2%). Cesarean section rate was 14%. The incidence of
      tachysystole was 18% and hypersystole 4%, but these situations were associated
      with abnormal fetal heart rate pattern (hyperstimulation) in only 3%. No maternal
      side effects and neonatal adverse effects were noted. CONCLUSIONS: Intravaginal
      misoprostol administration with low doses is an effective and safe method for
      labor induction in term pregnancies, with or without rupture of membranes.

PMID- 9544707
TI  - Prenatal strategies for reducing severe thalassemia in pregnancy.
AB  - OBJECTIVE: To describe the prenatal strategy in reducing new cases of severe
      thalassemia at Maharaj Nakorn Chiang Mai Hospital. The study design involved a
      prospective descriptive analysis set in Maharaj Nakorn Chiang Mai Hospital,
      Chiang Mai University. SUBJECTS: Pregnant women attending antenatal clinic.
      METHODS: The strategy included: (1) carrier identification by retrospective
      (history review) and prospective screening program; (2) the couples at risk were
      counseled and offered cordocentesis; (3) analysis of fetal blood with high
      performance liquid chromatography (HPLC) or electrophoresis; and (4) counseling
      for termination of pregnancy in case of affected fetus. The prospective screening
      consisted of testing for a carrier by a simple erythrocyte osmotic fragility test
      (EOFT) in women with no risk and testing the husbands of the women with abnormal
      tests. A pregnancy in which both of the couple were carriers was considered a
      risk. RESULTS: Cordocentesis was performed in 554 pregnancies at risk, 252 and
      302 from retrospective and prospective screening, respectively. Sixty of 252 of
      the first group had severe thalassemia. In the prospective screening program of
      12 680 women, 459 risk couples were identified, 302 pregnancies underwent
      cordocentesis and 53 (17.5%) had severe thalassemia. This strategy enabled us to
      identify 113 cases of severe thalassemia (Hb Bart's; 60, beta-thal entities; 53)
      from 554 cases at risk. CONCLUSION: The strategy proves valuable in the control
      of severe thalassemia. This extensive experience suggests the strategy be
      considered an effective way in the control of severe thalassemia in high
      prevalence areas.

PMID- 9544708
TI  - Birth weight, gestational age and medications during pregnancy.
AB  - OBJECTIVE: To determine the effect of medication on birth weight and gestational
      age in 29,004 healthy newborn infants born to mothers with or without treatment
      of drugs. METHOD: Birth weight and gestational age were evaluated in healthy
      control newborn infants in the population-based dataset of the Hungarian Case
      Control Surveillance of Congenital Abnormalities (1980-1991) using multiple
      regression analysis. RESULTS: Of 114 drugs used in more than 100 pregnant women,
      19 had a positive or negative impact. CONCLUSIONS: Further studies should be
      carried out to identify the possible mechanisms of medication and/or the maternal
      disorder for which this medication was given.

PMID- 9544709
TI  - Transcutaneous electrical nerve stimulation (TENS) for adjuvant pain-relief
      during labor and delivery.
AB  - OBJECTIVE: We examined the efficacy of transcutaneous electrical nerve
      stimulation (TENS) in general and the new Freemom TENS device (LifeCare, Israel)
      in particular, for pain relief during labor and delivery. METHODS: The study
      group consisted of 104 women. Forty-six nulliparas (44.2%) and 58 multiparas
      (55.8%), all of whom used the TENS device for pain relief during labor. All
      participants completed a questionnaire on the degree of pain relief afforded them
      by TENS during the delivery and related questions. The objective evaluation was
      based on the documented labor and delivery parameters including medical
      interventions during delivery. RESULTS: The majority of subjects (72% of the
      nulliparas and 69% of the multiparas) considered TENS effective for the relief of
      pain during labor. Most of them (67% of the nulliparas and 60% of the multiparas)
      responded positively to the use of TENS in future deliveries. Sixty-five percent
      of the multiparas considered TENS at least as effective as the other pain relief
      methods they had used before. TENS significantly reduced the duration of the
      first stage of labor P < 0.001 for nulliparas, P < 0.005 for multiparas and it
      significantly decreased the amount of analgesics administered to individual
      patients. No significant difference was found in fetal heart rate tracings, Apgar
      scores and cord blood pH between the study group and an equal number of matched
      controls who used other forms of pain management. CONCLUSIONS: TENS is an
      effective non-pharmacological, non-invasive adjuvant pain relief modality for use
      in labor and delivery. TENS application reduced the duration of the first stage
      of labor and the amount of analgesic drug administered. There were no adverse
      effects on mothers or newborns.

PMID- 9544710
TI  - Erythropoietin in amniotic fluid as a marker of chronic fetal hypoxia.
AB  - OBJECTIVE: To determinate the erythropoietin concentration in amniotic fluid in
      normal pregnancies and pregnancies with suspected hypoxia. METHOD: The
      erythropoietin concentration of 164 samples of amniotic fluid was determined by
      ELISA. The samples were taken by amniotomy during birth, as well as amniocentesis
      conducted during prenatal care. RESULTS: A distribution of 1.07-7.29 U/l (10th
      90th percentile) within the normal group (n = 106) was determined. Significantly
      elevated erythropoietin levels in amniotic fluid were determined in maternal
      hypertension (P = 0.039) and low birth-weight children (P = 0.0032). A
      correlation with the child's sex could be excluded. CONCLUSION: Elevated
      erythropoietin levels in amniotic fluid indicated chronic fetal hypoxia.

PMID- 9544711
TI  - Reproducibility of the revised American Fertility Society classification of
      endometriosis using laparoscopy or laparotomy.
AB  - OBJECTIVE: To assess the discrepancy between laparoscopic and laparotomic scoring
      methods using the revised American Fertility Society (AFS) classification of
      endometriosis. METHOD: In this prospective study, 84 patients with endometriosis
      were scored twice (laparoscopically and laparotomically) by the same subspecialty
      certified reproductive endocrinologist. The magnitude of inter-method variability
      was reported quantitatively by the S.D. of the differences in scores between the
      pairs. The differences in the mean endometriosis scores between the two methods
      were assessed by the paired Student's t-test. P < 0.05 was considered as
      statistically significant. Discrepancy between the two methods in the staging of
      endometriosis patients was presented by kappa measure of agreement. RESULT: There
      was considerable variability in the scores between the two scoring methods by the
      same observer. Among individual components of the scoring system, the greatest
      variability occurred in the ovarian endometriosis and cul-de-sac obliteration
      subscores, with the least variability observed for peritoneum endometriosis. The
      inter-method variation in score was sufficient to alter the endometriosis staging
      in 34.5% of patients, including a difference of two stages in 3.6% of patients.
      The kappa coefficient was 0.49, indicating fair-to-good agreement between the two
      scoring methods. CONCLUSION: Inter-method variability between laparoscopic and
      laparotomic scoring methods was high for ovarian endometriosis subscore using the
      revised AFS classification of endometriosis. Agreement in endometriosis staging
      between the two methods was fair to good.

PMID- 9544712
TI  - Effect of long-term hormone replacement therapy on the bone in ovariectomized
      women with cancer.
AB  - OBJECTIVE: To evaluate longitudinally the effectiveness of long-term hormone
      replacement therapy (HRT) in preserving the bone mineral density (BMD) over a 5
      year period in ovariectomized patients treated for gynecologic malignancies.
      METHODS: A total of 70 pre-menopausal women ovariectomized for gynecologic
      malignancies at our hospital were divided non-randomly into two groups: HRT (+)
      group (n = 59) and HRT (-) group (n = 11). HRT was administered in a sequential
      regimen of 0.625-1.25 mg conjugated estrogen for 24 days and 5-10 mg
      medroxyprogesterone acetate for 10 days. RESULTS: The BMD of the lumbar vertebrae
      decreased significantly in the HRT (-) group (pre-operative BMD was 91.8%, 91.0%
      and 91.3% at 1, 2 and 3 years post-ovariectomy), but no decrease in the BMD was
      observed in the HRT (+) group (pre-operative BMD was 98.4%, 99.0%, 99.4%, 98.8%
      and 98.7% at 1, 2, 3, 4 and 5 years post-ovariectomy); the difference in BMD
      between the two groups was statistically significant (P < 0.01). Serum alkaline
      phosphatase levels were significantly lower in the HRT (+) group than in the HRT
      (-) group (P < 0.01). There were four recurrences of cancer in the HRT (+) group.
      CONCLUSION: HRT appeared to have beneficial effects on bone metabolism by
      maintaining BMD for 5 years in ovariectomized patients for gynecologic
      malignancies.

PMID- 9544713
TI  - Single dose methotrexate therapy: application to interstitial ectopic pregnancy.
AB  - A woman with a small (6-mm gestational sac) interstitial pregnancy had complete
      resolution after medical therapy alone. A single cycle of methotrexate 50 mg/m2
      was used as outpatient treatment without any operative procedure either for
      diagnosis or intervention. The guidelines that have evolved for selection of
      women for single dose methotrexate treatment for both intrauterine and tubal
      ectopic pregnancies may be applicable to interstitial ectopic pregnancy as well.
      A suggested framework for treatment decisions is presented.

PMID- 9544714
TI  - Ovarian carcinoma in the third trimester.

PMID- 9544715
TI  - Perinatal Enterobius vermicularis infection.

PMID- 9544716
TI  - Feasibility of photodynamic endometrial ablation without anesthesia.

PMID- 9544717
TI  - Catamenial hemoptysis treated with a long-acting GnRH agonist.

PMID- 9544718
TI  - Assessment of second-look operations in malignant ovarian germ cell tumors.

PMID- 9544719
TI  - Pain control in abortion clinics.

PMID- 9544720
TI  - ACOG educational bulletin. Sexual assault. Number 242, November 1997 (replaces
      No. 172, September 1992). American College of Obstetricians and Gynecologists.

PMID- 9544721
TI  - ACOG committee opinion. Physician/patient responsibility for follow-up of
      diagnosis and treatment. Number 193, November 1997. Committee on Professional
      Liability. American College of Obstetricians and Gynecologists.

PMID- 9544722
TI  - ACOG practice patterns. Shoulder dystocia. Number 7, October 1997. American
      College of Obstetricians and Gynecologists.

PMID- 9544723
TI  - ACOG criteria set. Hysterectomy, abdominal or vaginal for abnormal uterine
      bleeding. Number 28, November 1997. Committee on Quality Assessment. American
      College of Obstetricians and Gynecologists.

PMID- 9544724
TI  - ACOG criteria set. Hysterectomy, abdominal or vaginal for chronic pelvic pain.
      Number 29, November 1997. Committee on Quality Assessment. American College of
      Obstetricians and Gynecologists.

PMID- 9544725
TI  - Lipid levels and peripheral vascular disease in diabetic and non-diabetic
      subjects.
AB  - Non-insulin dependent diabetes (NIDDM) is associated with an increased risk of
      peripheral vascular disease (PVD), but within the diabetic population the
      relationship between lipid profile and PVD has not been clearly defined. In this
      study we examined the association of lipid parameters and in particular low
      density lipoprotein (LDL) particle size, with the presence of PVD in subjects
      with and without NIDDM. 41 NIDDM patients and 31 non-diabetic subjects with PVD
      in the absence of rest pain or ulceration, defined by ankle-brachial index
      measurements and duplex scanning, were compared with 41 NIDDM and 31 euglycemic
      control subjects of comparable age and sex, without PVD. In both groups those
      with PVD were found to have significantly elevated triglycerides (2.7 [2.2-3.3]
      versus 1.9 [1.6-2.2] mmol/l; P < 0.05 in the diabetic group and 2.0 [1.6-2.3]
      versus 1.4 [1.1-1.5] mmol/l; P < 0.05 in the non-diabetic group), decreased
      apolipoprotein A1 (124 +/- 3 versus 139 +/- 5 mg/dl; P < 0.01 in the diabetic
      group and 133 +/- 4 versus 147 +/- 4 mg/dl; P < 0.05 in the non-diabetic group)
      and decreased LDL particle size (25.4 +/- 0.1 versus 25.8 +/- 0.1 nm; P < 0.01 in
      the diabetic group and 26.0 +/- 0.1 versus 26.3 +/- 0.1 nm; P < 0.05 in the non
      diabetic group). In the non-diabetic group apolipoprotein[a] (365 [239-554]
      versus 184 [17-266] U/l; P < 0.01), total cholesterol (6.3 +/- 0.2 versus 5.6 +/-
      0.2 mmol/l; P < 0.05), LDL cholesterol (4.1 +/- 0.2 versus 3.6 +/- 0.2 mmol/l; P
      < 0.05) and apolipoprotein B (146 +/- 8 versus 117 +/- 5 mg/dl; P < 0.05) were
      also found to be associated with PVD although these associations were not
      observed in the group with diabetes. In addition, 11 NIDDM subjects and 11 non
      diabetic subjects with rest pain or ulceration were compared to the corresponding
      groups with uncomplicated PVD and had lipid profiles with significantly lower
      levels of total cholesterol and LDL cholesterol. We conclude that the
      dyslipidemic profile characterized by increased triglyceride level, decreased
      apolipoprotein A1 level and small dense LDL is associated with uncomplicated PVD
      in both NIDDM and non-diabetic subjects.

PMID- 9544726
TI  - A novel mutation in Exon 4 of the low density lipoprotein receptor gene resulting
      in heterozygous familial hypercholesterolemia associated with decreased ligand
      binding.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by
      mutations in the low density lipoprotein (LDL) receptor gene. Currently,
      diagnosis of heterozygous FH relies on clinical phenotype; however, the use of
      clinical criteria for the diagnosis of heterozygous FH does not always permit
      unequivocable diagnosis of the disease. Molecular diagnosis of FH is clinically
      valuable especially in regions where founder mutations exist or where polygenic
      hypercholesterolemia is prevalent. In this paper we report the identification of
      a novel mutation, a cytosine to guanine substitution, at codon 152 in exon 4 of
      the LDL receptor gene in a Nova Scotian family clinically diagnosed with
      heterozygous FH. The mutation creates a recognition sequence for the restriction
      endonuclease BsrI, and can be readily detected by BsrI restriction analysis of a
      160 bp amplicon spanning the mutation. This analysis was used to show that the
      mutation segregated with the disease in this family and is the probable cause of
      FH in this kindred.

PMID- 9544727
TI  - C57BL/6 mice fed high fat diets as models for diabetes-accelerated
      atherosclerosis.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is a major risk factor for the
      development of atherosclerosis in humans. The development of an animal model that
      displays accelerated atherosclerosis associated with NIDDM will aid in
      elucidating the mechanisms that associate these disorders. C57BL/6 mice may
      provide such a model system. This strain becomes obese, hyperglycemic and insulin
      resistant when fed a high fat diet (diabetogenic diet) and is susceptible to
      atherosclerotic lesion development when fed a separate high fat diet containing
      cholesterol and bile acids (atherogenic diet). This report tests whether a diet
      commonly used to induce atherosclerosis also provokes a diabetic phenotype and
      whether a diet used to induce diabetes provokes the development of aortic fatty
      streak lesions. Mice of strains C57BL/6, C3H/He, BALB/c and seven recombinant
      inbred (RI) strains were fed an atherogenic diet for 14 weeks and glucose
      parameters were measured. No correlation was observed between atherosclerosis
      susceptibility and fasting insulin or glucose levels, or glucose clearance
      following short-term insulin or glucose treatment. Analysis of the RI strains
      suggested that multiple genes control these glucose metabolic parameters. Feeding
      the diabetogenic diet for 14 weeks to C57BL/6 mice induced obesity and diabetes
      and 2-fold increases in plasma lipoprotein concentrations. Also, small aortic
      sinus lipid deposits were observed in 40% of the mice. Thus, analysis of the
      diabetogenic diet fed C57BL/6 mouse may provide an important tool for further
      studies of diabetes accelerated vascular disease.

PMID- 9544728
TI  - Cardiovascular risk factors in non-insulin-dependent diabetics compared to non
      diabetic controls: a population-based survey among Asians in Singapore.
AB  - Cardiovascular risk factors were compared between 126 people with non-insulin
      dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random
      sample of people (Chinese, Malays, and Asian Indians) aged 40-69 years from the
      general population of Singapore. Data were adjusted for age and ethnicity. For
      both genders, people with NIDDM had higher mean body mass indices, waist-hip
      ratios and abdominal diameters. They also had a higher prevalence of
      hypertension, higher mean levels of fasting serum triglyceride, slightly lower
      mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels
      of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator
      (antigen). These factors are components of syndrome X (metabolic syndrome) and
      increase the risk of atherosclerosis and thrombosis. In contrast, there were no
      important differences for cigarette smoking, serum total and low-density
      lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and
      plasma prothrombin fragment 1 + 2. Females with NIDDM, but not males, had a
      higher mean serum fibrinogen level than non-diabetics, which could explain why
      NIDDM has a greater cardiovascular effect in females than males. Serum
      lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of
      serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls,
      but there were no important differences for plasma vitamins A, C and E, and serum
      selenium, which are anti-oxidants.

PMID- 9544729
TI  - Endothelial injury and leukocyte adherence in Hautchen preparations from coronary
      arteries and aorta of cynomolgus monkeys.
AB  - The aim was to describe the production of en face preparations (Hautchens) of the
      endothelium from the aorta and the coronary arteries of cynomolgus monkeys
      (Macaca fascicularis), to describe the morphology of the endothelium and to
      estimate endothelial injury. The present study describes, for the first time, the
      application of this technique to the coronary arteries. Numerous leukocytes
      (peroxidase-positive and -negative cells) were observed on the endothelium and a
      positive correlation between the numbers of adherent leukocytes and injured
      endothelial cells was found. A relatively leukocyte-independent measure of
      endothelial injury in the aorta was obtained by counting areas with a restricted
      number of leukocytes. The results indicated an even distribution and a relatively
      low frequency of injured endothelial cells along the arterial tree. The
      percentage of injured endothelial cells in LAD and LCX was 0.18 and 0.16, and in
      non-branched and circumostial areas of the descending thoracic aorta the
      corresponding figures were 0.22 and 0.28. There were, on average, 344 and 236
      adherent leukocytes/mm2 in the non-branched and circumostial areas of the
      descending thoracic aorta, respectively, compared to 13 in the LAD and 23 in the
      LCX. Proportionally more peroxidase-positive leukocytes (possibly granulocytes)
      were found on the coronary endothelium than on the aortic endothelium, and the
      peroxidase-positive cells were preferentially located around small artery
      branches in the coronary arteries. The foregoing data provide an estimate of the
      distribution and frequency of endothelial injury and adherent leukocytes at
      pathobiologically relevant arterial sites in unmanipulated cynomolgus monkeys, an
      animal frequently used in atherosclerosis research.

PMID- 9544730
TI  - Oxidized cholesterol in oxidized low density lipoprotein may be responsible for
      the inhibition of LPS-induced nitric oxide production in macrophages.
AB  - Previous work has shown that oxidized low density lipoprotein (Ox-LDL) inhibited
      lipopolysacchride (LPS)-induced nitric oxide (NO) production in macrophages. In
      this paper, the role of different components of Ox-LDL in the inhibitory effect
      was studied by measuring nitrite in media. Ox-LDL inhibited LPS-induced NO
      production in macrophage cell line J774.A1. When compared with Ox-LDL, native and
      acetylated LDL had a lesser effect on NO production. Pre-clearance of lipid
      hydroperoxides (LOOH) in Ox-LDL and removal of soluble thiobarbituric acid
      reactive substances (TBARS) in Ox-LDL solution by dialysis had no influence on
      the inhibitory effect of Ox-LDL. The protein moiety of Ox-LDL had no effect on NO
      production, but the lipid moiety inhibited NO production to about the same extent
      as intact Ox-LDL. Linoleic acid and phosphatidylcholine, the main components of
      LDL lipid, whether oxidized separately or together, had no effect on NO
      production. However, if linoleic acid and cholesterol oxidized together, there
      was very strong inhibition of NO production. Cholesterol oxidized alone also had
      some inhibitory effect. These results suggest that oxidized cholesterol in Ox-LDL
      might be responsible for the inhibition of NO production in macrophages.

PMID- 9544731
TI  - Inhibitory effect of inducible type nitric oxide synthase on oxidative
      modification of low density lipoprotein by vascular smooth muscle cells.
AB  - Oxidative modification of low density lipoprotein (LDL) plays an important role
      in atherogenesis. Inducible type nitric oxide synthase (iNOS) has been shown to
      be expressed in vascular smooth muscle cells (VSMC) of atherosclerotic arteries.
      Nitric oxide (NO) donors have been shown to inhibit metal ion- or cell-mediated
      oxidation of LDL. To elucidate whether NO produced by iNOS in VSMC inhibit
      oxidation of LDL, we investigated the effect of NO donors and iNOS-induction in
      VSMC on oxidation of LDL. NO donor, S-Nitroso-n-acetylpenicillamine (SNAP) or 3
      morpholinosydnonimine (SIN-1) (0.1-1.0 mmol/l) dose-dependently reduced copper
      induced oxidation of LDL as demonstrated by the inhibition of electrophoretic
      mobilities on agarose gels and the formation of thiobarbituric acid-reactive
      substances (TBARS) and conjugated dienes. Moreover, treatment with IL-1beta (5-50
      ng/ml) reduced the increases in electrophoretic mobilities on agarose gels and
      TBARS formation in association with increases in NO production. In addition,
      inhibition of NO production by NG-monomethyl-L-arginine monoacetate reduced the
      inhibitory effect of IL-1beta on LDL oxidation. These results indicate that NO
      release via iNOS action induced by cytokines in VSMC may play protective roles in
      oxidative modification of LDL during the atherosclerosis process.

PMID- 9544732
TI  - Amino-terminal fragment (1-34) of parathyroid hormone-related protein inhibits
      migration and proliferation of cultured vascular smooth muscle cells.
AB  - We investigated the effects of amino-terminal fragment (1-34) of parathyroid
      hormone-related protein [PTHrP-(1-34)] on the migration and proliferation of
      vascular smooth muscle cells (VSMCs). Cultured VSMCs (5-9th passage) obtained
      from the aortas of male Wistar rats were used in this study. Migration of VSMCs
      was assessed using a modified Boyden's chamber. Proliferation of VSMCs was
      evaluated by measuring [3H]thymidine incorporation and counting cell numbers.
      PTHrP-(1-34) inhibited 10% fetal bovine serum (FBS)-induced increase in migration
      of VSMCs (61% of control at 1 micromol/l) in a concentration-dependent manner.
      PTHrP-(1-34) also inhibited 5% FBS-induced increase in [3H]thymidine
      incorporation (37% of control at 1 micromol/l) and cell number of VSMCs (33% of
      control at 1 micromol/l) in a concentration-dependent manner. Parathyroid hormone
      (PTH)-(1-34) inhibited the migration and DNA synthesis of VSMCs to a similar
      extent. PTHrP-(7-34), a PTH/PTHrP receptor antagonist, significantly inhibited
      these effects of PTHrP and PTH. PTHrP-(1-34) also inhibited platelet-derived
      growth factor-BB (5 ng/ml)-induced migration and DNA synthesis of VSMCs. These
      findings suggest that PTHrP-(1-34) inhibits the migration and proliferation of
      VSMCs through PTH/PTHrP receptors.

PMID- 9544733
TI  - Dietary L-arginine decreases myointimal cell proliferation and vascular monocyte
      accumulation in cholesterol-fed rabbits.
AB  - L-arginine, the precursor of endogenous nitric oxide (NO), has been shown to
      enhance endothelial function and to reduce the progression of atherosclerosis in
      cholesterol-fed rabbits. In the present study, we investigated whether myointimal
      cell proliferation is enhanced in hypercholesterolaemic rabbit aorta and whether
      chronic treatment of the rabbits with L-arginine or with the NO synthase
      inhibitor L-NAME influences this proliferative response and vascular monocyte
      accumulation. Rabbits were fed 1% cholesterol or normal rabbit chow for 12 weeks.
      Subgroups of cholesterol-fed rabbits were treated with oral L-arginine (2.25%) or
      L-NAME (3 mg/dl) in drinking water. Myointimal cell proliferation was quantified
      in aortic segments by immunohistochemical detection of bromodeoxyuridine (BrdU)
      incorporation into nuclear DNA; vascular monocyte accumulation was assessed by
      immunohistochemistry using a monoclonal anti-macrophage/monocyte antibody (RAM
      11). Plasma levels of L-arginine and the endogenous NO synthase inhibitor, ADMA,
      were quantified by high-performance liquid chromatography (HPLC). Cholesterol
      feeding increased the aortic intima/media (I/M) ratio, which was not measurable
      in the control group, to 1.9 +/- 0.3. This was paralleled by enhanced cell
      proliferation (cholesterol, 2.4 +/- 0.2%; P < 0.05; control, 0.02 +/- 0.001% BrdU
      positive cells per 72 h) and vascular monocyte accumulation. Double
      immunostaining for BrdU and alpha-actin showed that about two thirds of the
      proliferating cells were smooth muscle cells. ADMA levels increased from 0.8 +/-
      0.1 micromol/l to 2.2 +/- 0.2 micromol/l in cholesterol-fed rabbits, but were
      unchanged by L-arginine or L-NAME treatment. Myointimal proliferation and
      intima/media ratios were correlated with ADMA plasma levels. Dietary L-arginine
      reduced monocyte accumulation by 85 +/- 2% (P < 0.05 vs cholesterol), myointimal
      cell proliferation (1.8 +/- 0.3% per 72 h; P < 0.05) and intimal thickening (I/M
      ratio: 0.7 +/- 0.2), whereas the inhibitor of NO synthase, L-NAME, further
      increased cell proliferation to 3.1 +/- 0.4% per 72 h (P < 0.05). No significant
      difference was observed in vascular monocyte infiltration between the cholesterol
      and L-NAME groups. We conclude that cell proliferation and vascular monocyte
      accumulation are enhanced in hypercholesterolaemic rabbit aorta. These
      atherogenic effects can be attenuated by dietary L-arginine. Decreased NO
      formation might underlie the enhanced monocyte accumulation and cell
      proliferation in hypercholesterolaemic rabbit aorta. The observed inhibition of
      cell proliferation adds to our understanding of the antiatherosclerotic effects
      of L-arginine in vivo.

PMID- 9544734
TI  - CI-1011 lowers lipoprotein(a) and plasma cholesterol concentrations in chow-fed
      cynomolgus monkeys.
AB  - Lipoprotein(a) (Lp(a)), which is generated through the covalent association of
      apolipoprotein(a) (apo(a)) and apo B-100-LDL, is an independent risk factor for
      several vascular diseases. Therefore, there is interest in developing therapies
      for lowering Lp(a). This investigation was carried out to determine the effect of
      CI-1011, a potent lipid regulator in rodents, on Lp(a) and other lipid parameters
      in cynomolgus monkeys (Macaca fascicularis). Nine healthy male monkeys on a
      normal chow diet were orally treated with CI-1011 at 30 mg/kg per day for 3
      weeks. Lp(a) and total cholesterol levels were significantly decreased after 1
      week and maximally reduced to 68 and 73% of control levels, respectively, after 3
      treatment weeks. The decreases in total cholesterol were mainly due to changes in
      low density lipoprotein (LDL). The LDL:HDL ratio decreased by 30%. Triglycerides
      were unaffected by treatment. Lp(a) and total cholesterol levels returned to
      pretreatment values after stopping treatment suggesting a direct effect of the
      compound on their inhibition. Further studies demonstrated that CI-1011 was
      effective at a low dose of 3 mg/kg per day after 1 week of administration. CI
      1011 also decreased apo B-100 to 80% of control levels, but this change was not
      sufficient to account for the Lp(a) lowering. There was also no correlation
      between the changes in Lp(a) and apo B-100 levels. Treatment of cynomolgus monkey
      primary hepatocyte cultures with CI-1011 resulted in a dose-dependent inhibition
      of Lp(a) levels suggesting a direct hepatic effect of the compound. Western blot
      analysis of the samples showed that changes in Lp(a) were associated mainly with
      decreased apo(a) (47%), but not apo B-100 (17%). These results demonstrate that
      CI-1011 effectively decreases Lp(a) levels both in vivo and in vitro.

PMID- 9544735
TI  - Effect of naturally reduced ovarian function on plasma lipoprotein and 27
      hydroxycholesterol levels in baboons (Papio sp.).
AB  - Female baboons over 15 years of age develop irregular menstrual cycles, an
      indication of declining ovarian function similar to that occurring in
      perimenopausal women. To determine the effect of declining ovarian function on
      plasma lipoprotein metabolism and plasma oxysterols, we measured plasma
      lipoprotein and 27-hydroxycholesterol levels in 86 female baboons from 15-28
      years of age with regular (n = 51) and irregular (n = 35) menstrual cycles. We
      sampled blood and liver while they were consuming a basal diet and after
      consuming a high cholesterol and high fat diet for 7 weeks. On the basal diet,
      baboons with irregular cycles had higher VLDL + LDL/HDL cholesterol ratios (P =
      0.034). After consuming the HCHF diet for 7 weeks, total plasma (P < 0.001) and
      VLDL + LDL (P < 0.001) cholesterol concentrations and VLDL + LDL/HDL sterol
      ratios (P < 0.001) increased in both cycle groups; whereas HDL cholesterol
      concentrations increased only in baboons with regular cycles (P = 0.009). As a
      result, HDL cholesterol concentrations (P = 0.006) were lower and VLDL + LDL/HDL
      cholesterol ratios (P = 0.002) were higher in baboons with irregular cycles on
      the HCHF diet. Plasma 27-hydroxycholesterol concentrations were higher in baboons
      with regular cycles than in those with irregular cycles on both basal (P = 0.018)
      and HCHF (P = 0.037) diets and were positively correlated (P < 0.001) with
      hepatic sterol 27-hydroxylase activities on both diets. Hepatic sterol 27
      hydroxylase activities were negatively correlated with the VLDL + LDL/HDL
      cholesterol ratios on the HCHF diet (r = -0.342, P = 0.033). These results
      suggest that declining ovarian function changes the plasma lipoprotein pattern to
      one that is more atherogenic. Ovarian failure is also associated with decreased
      concentrations of plasma 27-hydroxycholesterol (the major oxysterol of plasma),
      and the decrease in plasma 27-hydroxycholesterol concentration was due to the
      decrease in hepatic sterol 27-hydroxylase activity. The effects of ovarian
      failure on plasma lipoprotein metabolism and plasma 27-hydroxycholesterol may be
      mediated by the decreased production of estrogen in perimenopausal baboons. Thus,
      the perimenopausal baboon is an excellent model for menopause and can be used for
      studies that cannot be conducted in women.

PMID- 9544736
TI  - Dehydroepiandrosterone protects low density lipoproteins against peroxidation by
      free radicals produced by gamma-radiolysis of ethanol-water mixtures.
AB  - Oxidized low density lipoproteins (LDL) are believed to play a central role in
      the events that initiate atherosclerosis. Antioxidants have been shown to
      decrease the oxidation of LDL, leading to the diminution of atherosclerosis.
      Since it is well-known that decreased levels of dehydroepiandrosterone (DHEA) are
      linked to the development of atherosclerosis, we studied the modulation of the
      oxidation of LDL by DHEA. LDL were obtained from 10 healthy subjects and oxidized
      by free radicals produced by gamma-radiolysis of ethanol-water mixtures. The
      formation of conjugated dienes and thiobarbituric acid-reactive substances
      (TBARS), the vitamin E content, as well as the incorporation of 4-[14C]DHEA in
      LDL and the chemotactic effect of oxidized LDL in the presence of DHEA towards
      monocytes, were investigated. It was found that DHEA was able to inhibit the
      oxidation of LDL by reducing over 90% of the conjugated dienes and TBARS
      formation, as well as by reducing the vitamin E disappearance and significantly
      decreasing the chemotactic activity towards monocytes. Our results suggest that
      DHEA exerts its antioxidative effect by protecting the endogenous vitamin E of
      LDL.

PMID- 9544737
TI  - The 4G/5G polymorphism of the plasminogen activator inhibitor gene is associated
      with the time course of progression to acute coronary syndromes.
AB  - The 4G allele of the plasminogen activator inhibitor (PAI-I) gene is associated
      with increased PAI-I levels. Increased PAI-I levels have been reported to be
      associated with atherothrombotic events. However, the significance of the 4G/5G
      polymorphism of the PAI-I gene in the pathogenesis of ischemic heart diseases has
      not been determined. We assessed the 4G/5G polymorphism of the PAI-I gene in 500
      subjects including 148 normal controls, 23 subjects with normal coronary
      arteries, 28 subjects with a paradoxical acetylcholine response, 97 subjects with
      angina pectoris (AP) and 204 subjects with myocardial infarction (MI). We
      assessed the length of time between the first anginal pain and the onset of acute
      coronary syndromes (ACS) in the AP and MI subjects. Subjects who developed ACS
      within 2 months from the first anginal pain were categorized to have a rapid
      progression to ACS, and subjects who had had stable anginal pain more than 2
      months were placed in the non-ACS group. Subjects in the ACS group were younger
      than those in non-ACS group (P = 0.012) The frequency of the 5G/5G genotype of
      the PAI-I gene was lower in the ACS (0.228) than in the non-ACS group (0.093) (P
      = 0.003). Multiple logistic analyses revealed that a younger age (P = 0.028, odds
      ratio = 1.03) and the (4G/5G + 4G/4G) genotype of the PAI-I gene (P = 0.008, odds
      ratio = 2.68) were associated with the ACS group. We also assessed plasma PAI-I
      antigen levels in 78 subjects. Plasma PAI-I antigen levels in the non-ACS group
      were significantly lower than those in the ACS group (P = 0.050). Multiple
      regression analyses revealed that plasma PAI-I levels were determined by plasma
      insulin (P < 0.001) and the genotype of the PAI-I gene (P = 0.019). Higher plasma
      insulin levels and the (4G/5G + 4G/4G) genotype of the PAI-I gene were associated
      with higher plasma PAI-I levels. The 4G/5G polymorphism of the PAI-I gene
      influenced not only plasma PAI-I antigen levels but also the time course of the
      progression to ACS in patients with coronary atherosclerosis.

PMID- 9544738
TI  - Poloxamer 407-induced atherogenesis in the C57BL/6 mouse.
AB  - Poloxamer 407 (P-407) induces hyperlipidemia in the rat. It was the purpose of
      this investigation to determine if chronic P-407 administration would produce
      atherogenic arterial lesions in the C57BL/6 mouse, a strain reported to be
      susceptible to hyperlipidemia-induced atherosclerotic plaque formation. One
      injection (i.p.) of P-407 (0.5g/kg) produced hypercholesterolemia in the mouse
      that peaked at 24 h and returned to control levels by 96 h following treatment.
      Four groups of mice were maintained: (1) saline injected (C); (2) P-407-injected
      (0.5g/kg every 3rd day) (P); (3) P-407 injected plus cholic acid in the diet
      (PC); and (4) mice fed a high cholesterol (CHOL) diet containing cholic acid
      (HF). Mice from each group were sacrificed following 90, 145, 200, or 300 days of
      treatment. Plasma lipid concentrations, hepatic CHOL concentrations (145 and 300
      day), and aortic atherogenic lesion areas were measured. Plasma CHOL and
      triglyceride remained at control levels throughout the 300 days in the C group.
      CHOL of the HF animals plateaued at approximately 225 mg/dl. P-407 produced CHOL
      concentrations of 600 mg/dl in P mice and 1000-1500 mg/dl in PC animals. There
      was no lesion formation in C mice. However, by 90 days lesions were present in
      the three other groups. Size of the lesions progressed through day 300 with the
      largest lesions (184.33 + 27.99 mu2 x 10(-3)) being present in the PC mice. HF
      and P animals had lesions of 70.50 + 11.35 and 43.33 + 7.88 mu2 x 10(-3),
      respectively. This study provides an animal model where atherogenesis has been
      produced with hyperlipidemia induced using a chemical agent.

PMID- 9544739
TI  - Aminoguanidine has an anti-atherogenic effect in the cholesterol-fed rabbit.
AB  - Advanced glycosylation endproducts (AGEs) which result from the non-enzymatic
      interaction of proteins and glucose are implicated in the vasculopathy of
      diabetes and aging. Since aminoguanidine (A) inhibits the accumulation of AGEs,
      we explored its effects on the development of atherosclerosis. Male New Zealand
      white cross rabbits fed a high cholesterol (1%) diet were randomized to control
      (C) or increasing doses of A treatment (25, 50 and 100 mg/kg A body weight). The
      animals were sacrificed after 12 weeks. Sudan IV was used to stain the lipid
      containing plaques of the aortic arch, thoracic and abdominal aorta and the
      surface area occupied by atheroma was assessed. Increasing doses of A treatment
      were associated with reduction in plaque formation in the aorta. At a dose of 100
      mg/kg A, there was a 30, 49 and 48% reduction in plaque formation in the aortic
      arch, thoracic and abdominal aorta, respectively. There was a correlation between
      AGE levels and the degree of atheroma in these cholesterol fed rabbits (control,
      r = 0.75, P < 0.01; 100 mg/kg A, r = 0.59, P = 0.02). These data suggest that
      advanced glycation may participate in atherogenesis and raise the possibility
      that inhibitors of advanced glycation may retard this process.

PMID- 9544740
TI  - Elevated triglycerides and low HDL cholesterol in transgenic mice expressing
      human apolipoprotein A-I(Milano).
AB  - In general, plasma concentrations of high density lipoproteins (HDL) are
      inversely related to the incidence of coronary artery disease. One exception to
      this trend is individuals with apolipoprotein A-I(Milano) (apo A-IM), a molecular
      variant of apo A-I, which results in very low plasma apo A-I and HDL-cholesterol
      levels. Despite these low levels, and other lipoprotein defects, individuals with
      this mutation have no increased risk for cardiovascular disease. As a first step
      in proving why apo A-IM carriers appear to be protected from the pro-atherogenic
      effect of a low HDL, transgenic mice expressing apo A-IM were generated. Mice
      expressing either wild-type human apo A-I or apo A-IM, together with human apo A
      II, were crossed into mice lacking murine apo A-I. Apo A-IM/A-II mice had lower
      cholesterol and HDL plasma levels compared to apo A-I/A-II mice. Moreover, as in
      human carriers, apo A-IM mice were characterized by elevated triglyceride plasma
      levels and by the presence of a population of very small HDL particles. These
      results indicate that the expression of apo A-IM in a mouse model reproduces the
      major lipid/lipoprotein abnormalities observed in human carriers. Thus, apo A-IM
      transgenic mice appear to be a suitable model in which to assess whether the
      mutation has an anti-atherogenic effect.

PMID- 9544741
TI  - Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice.
AB  - Apo E3-leiden transgenic mice express human dysfunctional apo E variant and
      develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet.
      We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic
      mice using immunocytochemical methods in order to examine foam cell formation and
      determine whether advanced atherosclerotic lesions develop in these animals.
      Special attention was given to the presence of oxidized lipoproteins and
      expression of lipoprotein receptors. Plasma cholesterol levels in apo E3-leiden
      mice on an atherogenic diet increased from 2 to 36 mmol/l in 4 months. At this
      time apo E3-leiden mice had developed lesions, which ranged from early fatty
      streaks in thoracic and abdominal aorta to advanced lesions in aortic arch. Early
      fatty streaks were entirely composed of macrophages which also expressed
      scavenger receptors. Epitopes characteristic of oxidized LDL were present in
      macrophage-rich foam cells. Advanced atherosclerotic lesions also developed in
      apo E3-leiden mice including smooth muscle cell cap formation and erosion of the
      media. Macrophages and epitopes characteristic of oxidized LDL were present in
      core and shoulder regions. Scavenger receptors were expressed in macrophages in
      advanced lesions, whereas LDL-receptor-related protein (LRP) was mainly expressed
      in smooth muscle cells. It is concluded that: (1) macrophages are the major cell
      type in both early and advanced atherosclerotic lesions; (2) scavenger receptors
      and oxidized lipoproteins are present in lesion macrophages; and (3) LRP is
      mostly expressed in smooth muscle cells. Thus, lesions in apo E3-leiden
      transgenic mice have features in common with human atherosclerosis. Since lesion
      macrophages also retain their ability to synthesize endogenous apo E, apo E3
      leiden transgenic mouse may be a useful model for studies on the development and
      genetics of atherosclerosis.

PMID- 9544742
TI  - Psychosocial stress causes endothelial injury in cynomolgus monkeys via beta1
      adrenoceptor activation.
AB  - Current evidence links psychosocial factors to exacerbation of diet-induced
      atherosclerosis in monkeys via activation of the sympathetic nervous system.
      However, it is uncertain whether these factors can potentiate initial lesion
      formation, and do so even in the absence of dietary provocation, and whether any
      such effects can be prevented by beta-adrenergic blockade. As endothelial injury
      has been considered an initiating event in atherogenesis, we studied the effect
      of psychosocial stress on endothelial integrity in 48 adult male cynomolgus
      monkeys (Macaca fascicularis). All animals were housed in 12 social groups of
      four monkeys each for 11 weeks. The monkeys in half of the groups were exposed to
      a socially unstable ('stressed') condition for 72 h and received saline (n = 8),
      a lipophilic beta1-blocker (metoprolol, 0.30 mg/kg per h; n = 8), or hydrophillic
      beta1-blocker (atenolol, 0.15 mg/kg per h; n = 8). The remaining six social
      groups were assigned to the socially stable (non-stressed) condition; for 72 h
      these animals all remained in their social groups and were similarly treated with
      saline (n = 8), metoprolol (n = 8), or atenolol (n = 8). The frequency of IgG
      positive (injured) endothelial cells was estimated on en face (Hautchen)
      preparations from the thoracic aorta and coronary arteries. Psychosocial stress
      caused a significant increase in the number of injured endothelial cells in the
      circumostial areas of the descending thoracic aorta in the placebo group (0.3 vs.
      0.8%, P < 0.02), an effect that had not been demonstrated previously. Moreover,
      beta-blockade significantly (P < 0.01) inhibited the stress effect, with no
      differences between the two beta-blocking agents. The number of injured
      endothelial cells in the non-branched portions of the aorta and coronary arteries
      were low and indistinguishable among groups; irregularities in the size and
      location of branching points in the coronary arteries precluded analysis of these
      sites. This study demonstrated that psychosocial stress induces endothelial
      injury, and that this effect is mediated via beta1-adrenoceptor activation.

PMID- 9544743
TI  - Troglitazone enhances glucose uptake and inhibits mitogen-activated protein
      kinase in human aortic smooth muscle cells.
AB  - The thiazolidinedione analogue troglitazone is an antidiabetic agent that
      improves insulin resistance in rodents and humans. Although coronary artery
      disease is common in patients with the insulin resistance syndrome, the effects
      of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We
      therefore examined the effects of troglitazone on cell growth and glucose uptake
      in human aortic SMC. Mitogen-activated protein (MAP) kinase activity and glucose
      transporter (Glut) 1 mRNA levels were also studied. In the absence of
      troglitazone, insulin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC
      and troglitazone suppressed the increase of DNA synthesis in a dose-dependent
      manner. This growth suppression was accompanied by inhibition of MAP kinase
      activity. On the other hand, troglitazone significantly increased Glut 1 mRNA and
      enhanced glucose uptake in SMC. These results suggest that troglitazone affects
      the insulin signaling pathways in SMC and suppresses growth while promoting
      glucose uptake. Our findings support the application of troglitazone as an
      inhibitor of SMC proliferation in patients with insulin resistance.

PMID- 9544744
TI  - The effect of homocysteine on DNA synthesis in cultured human vascular smooth
      muscle.
AB  - Elevated plasma homocysteine is an established risk factor for vascular disease
      although the mechanisms are unclear. Homocysteine has been reported to stimulate
      DNA synthesis and proliferation in rat aortic smooth muscle cells. Human vascular
      smooth muscle cells (HVSMC) from saphenous veins (n = 8), internal mammary
      arteries (n = 6) and umbilical arteries (n = 2) were studied. To reflect DNA
      synthesis, 3H-thymidine incorporation, during 24 h exposure to homocysteine in
      concentrations from 0.0625 to 10 mM, was studied. Incorporation was significantly
      increased up to 0.5 or 1 mM and thence was progressively depressed, the maximum
      stimulation being 24 +/- 5(S.E.)% in vein (P < 0.005) and 34 +/- 4% in mammary
      artery (P < 0.001) while incorporation fell to approximately 25% of the control
      values at 10 mM (P < 0.001). Qualitatively similar results were obtained in
      umbilical arteries. Homocysteine had a biphasic effect on DNA synthesis in
      cultured HVSMC but the higher inhibitory concentrations are well above those
      commonly found in vivo. While the conditions of exposure to homocysteine render
      close analogy to the clinical situation impossible, homocysteine can stimulate
      HVSMC, offering one possible mechanism for the involvement of homocysteine in the
      pathogenesis of atherosclerosis.

PMID- 9544745
TI  - Influence of genotype at the low density lipoprotein (LDL) receptor gene locus on
      the clinical phenotype and response to lipid-lowering drug therapy in
      heterozygous familial hypercholesterolaemia. The Familial Hypercholesterolaemia
      Regression Study Group.
AB  - The relationship between molecular defect and clinical phenotype has been
      examined in 42 patients with heterozygous familial hypercholesterolaemia (FH) and
      premature coronary heart disease. The defined defects included mutations in the
      low density lipoprotein (LDL)-receptor gene (23/42) or the apolipoprotein B
      Arg3500Gln mutation (5/42). Mean LDL-cholesterol was higher, both before and
      during treatment with simvastatin and bile acid sequestrants, in patients
      predicted as having a 'severe' mutation than in those with a 'mild' mutation
      (8.72 +/- 2.02 mmol/l vs 6.63 +/- 1.8, P = 0.05 before and 4.51 +/- 0.90 mmol/l
      vs 3.19 +/- 0.58, P = 0.05 during treatment). Maximum inducible LDL-receptor
      activity in cultured lymphoblasts was inversely correlated with LDL-cholesterol
      before (r2 = 0.499, P = 0.002) and during (r2 = 0.478, P = 0.004) treatment in
      patients with a defined mutation in the LDL-receptor gene, but not in the 14
      patients with no detectable molecular defect. LDL-cholesterol concentrations
      before and during treatment were significantly correlated in patients with a
      defined LDL-receptor gene mutation (r2 = 0.548, P = 0.0001), but not in those
      with no detectable genetic defect. All these correlations were weak, however and
      there were no differences in the response to treatment in terms of either
      relative reduction or absolute decrease in LDL-cholesterol concentration between
      patients with different LDL-receptor defects. We conclude that only part of the
      variable phenotype of heterozygous FH patients is explained by different LDL
      receptor defects and that other factors determine the severity of their
      hypercholesterolaemia and the onset of coronary disease.

PMID- 9544747
TI  - Why plasma should not be used to study paraoxonase.

PMID- 9544746
TI  - Low density lipoprotein receptor mutations in a selected population of
      individuals with moderate hypercholesterolemia.
AB  - To evaluate mutations in the low density lipoprotein receptor (LDL-R) gene in
      moderate primary hypercholesterolemia, a combination of polymerase chain reaction
      (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing, was
      used to screen the LDL-R gene in a selected population of 82 unrelated
      individuals with moderate elevation of plasma LDL-C [mean 4.55 +/- 0.55 mmol/l
      (176.4 +/- 21.6 mg/dl)]. Four subjects (5%) were found to be heterozygotes for
      missense mutations in the LDL-R gene. These mutations were located in four
      different exons (exons 6, 7, 15 and 17) and all alters highly conserved residues
      of LDL-R protein. None of these mutations were detected in 79
      normocholesterolemic individuals. The mutation in exon 15 (T705I) was previously
      reported in a compound heterozygote for familial hypercholesterolemia (FH). In
      the proband carrying the mutation in exon 17 (R793Q), an in vivo LDL turnover
      study was performed and it demonstrated a reduction of LDL catabolism. These
      findings demonstrate that mutations in the LDL-R may occur in primary moderate
      hypercholesterolemia. They also extend the concept that some FH patients may
      present with a mild phenotype.

PMID- 9544748
TI  - Can endothelial cells accumulate lipids?

PMID- 9544749
TI  - A farewell to harms: experts debate global disease eradication efforts.

PMID- 9544751
TI  - From the Centers for Disease Control and Prevention. Progress toward
      poliomyelitis eradication--Bangladesh, 1995-1997.

PMID- 9544750
TI  - FDA funding problems imperil safety of biological products in the United States.

PMID- 9544752
TI  - From the Centers for Disease Control and Prevention. Enhanced medical assessment
      strategy for Barawan Somali refugees--Kenya 1997.

PMID- 9544753
TI  - A piece of my mind. After the miracle.

PMID- 9544754
TI  - Gatekeeping: good or bad, but never indifferent.

PMID- 9544755
TI  - Gatekeeping: good or bad, but never indifferent.

PMID- 9544756
TI  - Gatekeeping: good or bad, but never indifferent.

PMID- 9544757
TI  - Gatekeeping: good or bad, but never indifferent.

PMID- 9544758
TI  - Gatekeeping: good or bad, but never indifferent.

PMID- 9544759
TI  - Risk adjustment, quality assessment, and process of care.

PMID- 9544760
TI  - Risk adjustment, quality assessment, and process of care.

PMID- 9544761
TI  - Prevention and management of latex allergy.

PMID- 9544762
TI  - Varicella infection in adults reporting prior varicella.

PMID- 9544763
TI  - Medication dispensing and Medicaid managed care.

PMID- 9544764
TI  - Reengineering quality in managed care.

PMID- 9544765
TI  - Frequency of breast cancer attributable to BRCA1 in a population-based series of
      American women.
AB  - CONTEXT: Previous studies of BRCA1 mutation prevalence have been based on high
      risk groups, yielding estimates that do not reflect the experience of the general
      population of US patients with breast cancer. OBJECTIVE: To determine prevalence
      of known disease-related mutations and other variants in BRCA1 and how it differs
      by race, age at diagnosis, and family history status in a population-based sample
      of white and black patients with breast cancer unselected for family history.
      DESIGN: Case-control study. SETTING: A 24-county area of central and eastern
      North Carolina. PARTICIPANTS: Cases were women aged 20 to 74 years diagnosed as
      having a first invasive breast cancer between May 1993 and June 1996. Controls
      were frequency matched to cases by 5-year age range and race. The first 211 cases
      and 188 controls regardless of race and the subsequent 99 cases and 108 controls
      of African American ancestry are included in this report. MAIN OUTCOME MEASURE:
      Germline variants at any site in the coding sequence, splice junctions, 5'
      untranslated region, or 3' untranslated region of the BRCA1 gene were analyzed in
      cases, and selected variants were analyzed in controls. Screening was performed
      using multiplex single-strand conformation analysis, with all potential variants
      confirmed using genomic sequencing. RESULTS: Three of 211 patients with breast
      cancer had disease-related variants at BRCA1, all of which were protein
      truncating mutations. After adjustment for sampling probabilities, the proportion
      of patients with breast cancer with disease-related variants was 3.3% (95%
      confidence interval, 0%-7.2%) in white women and 0% in black women. Young age at
      diagnosis alone did not predict BRCA1 carrier status in this population. In white
      women, prevalence of inherited mutation was 23% for cases with family history of
      ovarian cancer, 13% for cases from families with at least 4 cases of breast
      cancer with or without ovarian cancer, and 33% for cases from families with both
      breast and ovarian cancer and at least 4 affected relatives. Because these
      results are based on few families at the highest levels of risk, confidence
      intervals around these estimates are wide. An additional 5 patients had rare
      missense mutations or a single amino acid deletion, the biological significance
      of which is unknown. In black women, a variant in the 3' untranslated region was
      statistically significantly more common in cases than in controls. CONCLUSIONS:
      These data suggest that in the general US population, widespread screening of
      BRCA1 is not warranted. In contrast, BRCA1 mutations are sufficiently frequent in
      families with both breast and ovarian cancer, or at least 4 cases of breast
      cancer (at any age), that genotyping might be considered. The emerging picture of
      BRCA1 population genetics involves complex interactions of family history, age,
      and genetic ancestry, all of which should be taken into account when considering
      testing or interpreting results.

PMID- 9544766
TI  - BRCA1 mutations and breast cancer in the general population: analyses in women
      before age 35 years and in women before age 45 years with first-degree family
      history.
AB  - CONTEXT: Studies of high-risk families with multiple early-onset cases of breast
      cancer have been useful for assessing the type and spectrum of germline mutations
      on the BRCA1 gene, but do not provide guidance to women with modest family
      history profiles. Thus, studies of women from the general population are needed
      to determine the BRCA1 mutation frequency in women perceived to be at high risk,
      and to develop profiles of those most likely to be carriers. OBJECTIVE: To
      characterize frequency and spectrum of germline BRCA1 mutations in 2 categories
      of women identified via population-based studies hypothesized to be at increased
      risk of carrying such mutations: those diagnosed as having breast cancer before
      age 35 years and those diagnosed before age 45 years who have first-degree breast
      cancer family history. DESIGN: Study subjects were drawn from 2 population-based
      case-control studies of breast cancer in young women on the basis of their family
      history or their age of diagnosis. Cases were younger than 35 years or were
      younger than 45 years with first-degree family history at the time of breast
      cancer diagnosis and were ascertained via a population-based cancer registry, and
      controls (women without breast cancer) were identified via random-digit dialing.
      SETTING: Three counties in western Washington State. MAIN OUTCOME MEASURE: BRCA1
      germline mutations in study subjects identified in DNA from peripheral blood
      lymphocytes by single-strand conformation polymorphism analysis using primer
      pairs that span the BRCA1 coding region and intron-exon boundaries. RESULTS: Of
      193 women diagnosed as having breast cancer before age 35 years, none of whom
      were selected on the basis of family history status, 12 (6.2%, 95% confidence
      interval [CI], 3.2%-10.6%) had germline BRCA1 mutations. In 208 women diagnosed
      before age 45 years who had first-degree breast cancer family history, 15 (7.2%,
      95% CI,4.1%-11.6%) had germline mutations in BRCA1. In both groups, there were
      variations in mutation frequency noted by age and by family history. Mutation
      frequency decreased with increasing age of diagnosis. Higher proportions of
      mutations were seen in cases with at least 1 relative diagnosed as having breast
      cancer before age 45 years, in cases with greater numbers of affected relatives,
      and those with ovarian cancer family history. Mutation frequency did not vary by
      bilateral breast cancer family history. No frameshift or nonsense mutations were
      observed in 71 control women with a first-degree family history, although
      missense changes of unknown significance were seen in cases and controls.
      CONCLUSIONS: Women with BRCA1 germline mutations lacked a common family history
      profile. Also, a large proportion of the women with a first-degree breast cancer
      family history and women diagnosed as having breast cancer before age 35 years
      did not carry germline BRCA1 mutations. Hence, while early-onset disease and a
      strong breast cancer family history may be useful guidelines for checking BRCA1
      status, these findings on women drawn from the general population suggest that it
      may be difficult to develop BRCA1 mutation screening criteria among women with
      modest family history profiles.

PMID- 9544768
TI  - Relationship of physical activity and television watching with body weight and
      level of fatness among children: results from the Third National Health and
      Nutrition Examination Survey.
AB  - CONTEXT: Physical inactivity contributes to weight gain in adults, but whether
      this relationship is true for children of different ethnic groups is not well
      established. OBJECTIVE: To assess participation in vigorous activity and
      television watching habits and their relationship to body weight and fatness in
      US children. DESIGN: Nationally representative cross-sectional survey with an in
      person interview and medical examination. SETTING AND PARTICIPANTS: Between 1988
      and 1994, 4063 children aged 8 through 16 years were examined as part of the
      National Health and Nutrition Examination Survey III. Mexican Americans and non
      Hispanic blacks were oversampled to produce reliable estimates for these groups.
      MAIN OUTCOME MEASURES: Episodes of weekly vigorous activity and daily hours of
      television watched, and their relationship to body mass index and body fatness.
      RESULTS: Eighty percent of US children reported performing 3 or more bouts of
      vigorous activity each week. This rate was lower in non-Hispanic black and
      Mexican American girls (69% and 73%, respectively). Twenty percent of US children
      participated in 2 or fewer bouts of vigorous activity perweek, and the rate was
      higher in girls (26%) than in boys (17%). Overall, 26% of US children watched 4
      or more hours of television per day and 67% watched at least 2 hours per day. Non
      Hispanic black children had the highest rates of watching 4 or more hours of
      television per day (42%). Boys and girls who watch 4 or more hours of television
      each day had greater body fat (P<.001) and had a greater body mass index (P<.001)
      than those who watched less than 2 hours per day. CONCLUSIONS: Many US children
      watch a great deal of television and are inadequately vigorously active. Vigorous
      activity levels are lowest among girls, non-Hispanic blacks, and Mexican
      Americans. Intervention strategies to promote lifelong physical activity among US
      children are needed to stem the adverse health consequences of inactivity.

PMID- 9544767
TI  - A randomized, double-blind trial comparing combinations of nevirapine,
      didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The
      Netherlands, Canada and Australia Study.
AB  - CONTEXT: Current guidelines recommend that individuals infected with the human
      immunodeficiency virus type 1 (HIV-1) be treated using combinations of
      antiretroviral agents to achieve sustained suppression of viral replication as
      measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged
      remission of the disease. However, until recently, many drug combinations have
      not led to sustained suppression of HIV-1 RNA. OBJECTIVE: To compare the
      virologic effects of various combinations of nevirapine, didanosine, and
      zidovudine. DESIGN: Double-blind, controlled, randomized trial. SETTING:
      University-affiliated ambulatory research clinics in Italy, the Netherlands,
      Canada and Australia (INCAS). PATIENTS: Antiretroviral therapy-naive adults free
      of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and
      0.60x10(9)/L (200-600/microL). INTERVENTION: Patients received zidovudine plus
      nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine
      placebo), or zidovudine plus didanosine plus nevirapine. MAIN OUTCOME MEASURE:
      Plasma HIV-1 RNA. RESULTS: Of the 153 enrolled patients, 151 were evaluable. At
      week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the
      triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine
      groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA
      levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the
      triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine
      groups, respectively (P<.001). Viral amplification was attempted in 59 patients
      at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19,
      and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus
      didanosine, and zidovudine plus nevirapine groups, respectively. Among patients
      from whom virus could be amplified, resistance to nevirapine was found in all 11
      patients receiving zidovudine plus nevirapine and in all 5 patients receiving
      triple drug therapy. Rates of disease progression or death were 23% (11/47), 25%
      (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus
      didanosine, and triple drug therapy groups, respectively (P=.08). CONCLUSIONS:
      Triple drug therapy with zidovudine, didanosine, and nevirapine led to a
      substantially greater and sustained decrease in plasma viral load than the 2-drug
      regimens studied. Our results also suggest that suppression of viral replication,
      as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of
      quantitation of the most sensitive test available, may at least forestall the
      development of resistance.

PMID- 9544769
TI  - Directly observed therapy for treatment completion of pulmonary tuberculosis:
      Consensus Statement of the Public Health Tuberculosis Guidelines Panel.
AB  - OBJECTIVE: To evaluate evidence on the relative effectiveness of directly
      observed therapy in achieving treatment completion for pulmonary tuberculosis.
      PARTICIPANTS: A panel of 11 practitioners representing the public health,
      behavioral, and clinical management of tuberculosis was convened by the Council
      on Linkages Between Academia and Public Health Practice in 1995 to develop public
      health guidelines for tuberculosis treatment completion. EVIDENCE: English
      language articles identified through MEDLINE (1966 to August 1, 1996) with
      original data on directly observed therapy, supervised therapy, compliance,
      treatment completion, case management, and treatment adherence for tuberculosis.
      CONSENSUS PROCESS: Each eligible article underwent structured review by at least
      2 panel members for study design, sample size, evaluation methods, and treatment
      completion as the primary outcome. The full panel was convened twice, with
      intercurrent small group meetings, conference calls, and summary workshop to
      review findings. Recommendations made through this process were drafted by the
      panel chair and circulated twice for additional panel comments. CONCLUSIONS:
      Treatment completion rates for pulmonary tuberculosis are most likely to exceed
      90%, as recommended by the Centers for Disease Control and Prevention, when
      treatment is based on a patient-centered approach using directly observed therapy
      with multiple enablers and enhancers. Other less intensive interventions,
      including nonsupervised strategies and modified approaches to directly observed
      therapy, are unlikely to achieve this recommended treatment completion goal.
      Directly observed therapy also appears to be cost-effective compared with self
      administered therapy, although data on cost-effectiveness are limited.

PMID- 9544770
TI  - A 66-year-old woman with ulcerative colitis.

PMID- 9544771
TI  - A 27-year-old woman with migraine headaches, 1 year later.

PMID- 9544772
TI  - BRCA1 testing--advances and retreats.

PMID- 9544773
TI  - HIV treatment strategies: planning for the long term.

PMID- 9544774
TI  - Does television cause childhood obesity?

PMID- 9544775
TI  - Attachment of group B streptococci to macrophages is mediated by a 21-kDa
      protein.
AB  - Group B Streptococcus (GBS) is able to bind to human macrophages in vitro in the
      absence of exogenous opsonins. The exact mechanisms that mediate this attachment
      are unclear. This study was undertaken to determine what protein adhesins are
      present on the surface of GBS that mediate attachment to macrophages. We have
      identified a 21-kDa protein from the envelope of GBS type III that directly binds
      to macrophages as determined by Western blot analysis. Antiserum against this
      protein was able to inhibit binding of GBS to macrophages by greater than 80% as
      measured by flow cytometry. Antiserum against the 21-kDa protein cross-reacted
      with 21-kDa proteins from GBS type Ib, type II, type III (COH31 and MR732) and
      type IV, as well as Staphyloccus epidermidis, but not GBS type Ia, Listeria
      monocytogenes or Enterococcus faecalis. This protein may be important in
      mediating the attachment of GBS to macrophages in an opsonin-poor environment.

PMID- 9544776
TI  - Effect of trifluoperazine on in vitro ATP synthesis by Mycobacterium leprae.
AB  - The effect of trifluoperazine (TFP), a calmodulin antagonist, was investigated on
      in vitro ATP levels of human derived Mycobacterium leprae. M. leprae were
      obtained from biopsies from multi-bacillary forms of leprosy and were incubated
      in a modified Dubos medium system which supports limited in vitro synthesis of M.
      leprae. This incubation was carried out in the absence and presence of different
      concentrations of trifluoperazine. Samples for estimation of bacillary ATP levels
      were taken at day 0 and at 14 days of incubation. TFP inhibited ATP levels in M.
      leprae and this inhibitory effect was marginal at 2.5 microg ml(-1) (35%
      inhibition), highly significant at 5 microg ml(-1) (87% inhibition) and almost
      total at 10 microg ml(-1) (98.5% inhibition). This compound appears to have
      potential as an anti-leprotic drug and also as a broad spectrum anti
      mycobacterial agent in view of its anti-tubercular activity reported earlier.

PMID- 9544777
TI  - Sequence analysis of a compound coding-region microsatellite in Candida albicans
      resolves homoplasies and provides a high-resolution tool for genotyping.
AB  - Sequence diversity at a coding-region microsatellite locus of two diploid Candida
      species was surveyed. Twenty-one alleles from fourteen strains of Candida
      albicans and three alleles from two strains of the closely related Candida
      dubliniensis were sequenced. Results show independent length variation in two
      contiguous hexanucleotide repeats, one non-contiguous hexanucleotide repeat, and
      two non-contiguous trinucleotide repeats within a 120 bp coding region. A
      neighboring, non-repetitive 120 bp region showed no variation. The information
      density of sequence polymorphisms in this region provides a powerful tool for
      genotyping microorganisms in epidemiological studies, yielding detailed
      resolution of closely related strains, and clearly distinguishing the two species
      studied here. The individual length-variable repeat regions are very short (2-8
      repeats), demonstrating that even very short microsatellites can show high levels
      of length variability when surrounded by similarly repetitive DNA. Extensive
      homoplasy was discovered among the C. albicans alleles, with the majority of
      overall length categories consisting of alleles with more than one sequence. Our
      results show that microsatellite length alone should not be used to assume either
      sequence identity or identity by descent. Microsatellite length mutations appear
      to have generated the high degree of both inter- and intraspecific polymorphism
      seen at the ERK1 locus, and form an island of variability in an otherwise well
      conserved gene.

PMID- 9544779
TI  - Immunochemical characterization of an IgG-binding protein of Streptococcus suis.
AB  - Several bacterial species express surface proteins with affinity for the constant
      region (Fc) of immunoglobulin (Ig) of different animal species. Previous studies
      from our group have reported the presence of an IgG-binding protein in various
      serotypes of Streptococcus suis. This molecule was also shown to bind in a non
      immune fashion chicken IgY and to our knowledge this characteristic is unique. In
      the present study, by dot-blotting, we showed that the native protein, obtained
      by affinity chromatography, reacted more strongly with IgG from various animal
      species than the denatured material. Using a competitive enzyme-linked
      immunosorbent assay the affinity of the native 60-kDa protein (previously
      identified as a 52-kDa protein) towards IgG of various animal species was
      compared to pig IgG. Bovine, goat and human IgG were able to compete effectively
      with pig IgG whereas chicken IgY constituted a poor competitor. Peptide mapping
      analysis using denatured protein indicated that pig and bovine IgG recognized the
      same proteolytic fragment whereas chicken IgY did not. The smallest proteolytic
      fragment that retained the binding activity towards the IgG of the different
      animal species tested had a molecular mass of approximately 40 kDa. Fragments
      with Mr < 40 kDa showed specific binding activities. That is, the smallest
      fragment binding pig and bovine IgG had a Mr of 30 kDa whereas for goat and human
      IgG a fragment of less than 16 kDa still showed binding activity. Finally, we
      observed that antisera raised against a heat-shock protein of Pseudomonas
      aeruginosa reacted with the 60-kDa S. suis protein indicating that the S. suis 60
      kDa protein is a member of the 60-kDa hsp family that possesses the
      characteristic of binding in a non-immune way mammalian IgG and chicken IgY.

PMID- 9544778
TI  - A Salmonella typhimurium strain genetically engineered to secrete effectively a
      bioactive human interleukin (hIL)-6 via the Escherichia coli hemolysin secretion
      apparatus.
AB  - Human interleukin-6 (hIL-6) cDNA was genetically fused with the Escherichia coli
      hemolysin secretorial signal (hlyA[S]) sequence in a plasmid vector. Recombinant
      E. coli XL-1 Blue and attenuated Salmonella typhimurium secreted a 30 kDa hIL-6
      HlyA(S) fusion protein, with an additional form of higher apparent molecular mass
      produced by S. typhimurium. In S. typhimurium cultures hIL-6-HlyA(S)
      concentrations entered a plateau at 500 to 600 ng ml(-1) culture supernatant. In
      contrast to E. coli XL-1 Blue, in S. typhimurium culture supernatants hIL-6
      HlyA(S) was accumulated faster reaching three-fold higher maximal concentrations.
      The cell proliferating activity of hIL-6-HlyA(S) fusion protein(s) was equivalent
      to that of mature recombinant hIL-6. Furthermore. hIL-6-secreting S. typhimurium
      were less invasive than the attenuated control strain. Therefore, the bulky
      hemolysin secretorial peptide at the C-terminus of the fusion protein does not
      markably affect hIL-6 activity, suggesting that the hemolysin secretion apparatus
      provides an excellent system to study immunomodulatory effects of in situ
      synthesized IL-6 in Salmonella vaccine strains.

PMID- 9544780
TI  - Characterization of antigens recognized by new monoclonal antibodies raised
      against culture filtrate proteins of Mycobacterium bovis bacillus Calmette
      Guerin.
AB  - Effective protection against Mycobacterium tuberculosis may be achieved in
      experimental animals by immunization with proteins secreted by tuberculous
      bacilli in the extracellular milieu during growth. In this study, monoclonal
      antibodies were raised against Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      culture filtrate proteins or live BCG, in an attempt to identify novel
      mycobacterial secretion antigens: the localization of the antigens recognized by
      the monoclonal antibodies within the mycobacterial cell was studied and
      interspecies reactivity was also investigated. The monoclonal antibodies obtained
      recognized proteins of molecular mass ranging from 5 to 82 kDa, with a prevailing
      frequency in the 30 kDa region. Three of the monoclonal antibodies recognized
      proteins present only in culture filtrates, one reacted with a cytoplasmic
      antigen, while the remaining antibodies recognized components which were mainly
      associated with the cell wall and the cytoplasmic membrane. The chemical nature
      and possible identity of the antigens was checked. Three monoclonal antibodies
      are likely to react with novel mycobacterial antigens of 5, 42 and 82 kDa,
      respectively.

PMID- 9544781
TI  - Induction of abnormal respiratory sounds by capsaicin in rats previously infected
      with Bordetella pertussis.
AB  - Sprague Dawley rats, previously infected with Phase-I Bordetella pertussis,
      developed more severe abnormal respiratory sounds than normal animals, but not
      coughing, when exposed to aerosolized capsaicin, one of several cough-inducing
      agents tested. Stethoscope examination suggested that greater production of
      pulmonary mucus might be occurring after capsaicin challenge of the infected
      animals, compared to the uninfected controls. Rats of three other strains gave
      characteristically different responses from the Sprague Dawleys. The
      administration of capsaicin to B. pertussis-infected rats may provide useful
      insights into the pathophysiology of excess mucus secretion in human pertussis.

PMID- 9544782
TI  - Identification of mycobacterial HSP70 reactive human T cell clones discriminating
      between M. tuberculosis and M. leprae.
AB  - M. tuberculosis reactive CD4+ T cell clones were established from a BCG
      vaccinated donor and tested for proliferative responses against complex
      mycobacterial antigens like M. tuberculosis, M. leprae, and PPD, as well as the
      recombinant M. tuberculosis HSP70 and HSP65 antigens from both M. tuberculosis
      and M. leprae. This screening permitted the identification of T cell clones
      specifically recognizing the mycobacterial HSP70 or HSP65 antigen. All HSP65
      reactive T cell clones were cross-reactive for M. tuberculosis and M. leprae,
      whereas three HSP70 reactive T cell clones only recognized M. tuberculosis. In
      addition, HLA typing and blocking experiments with anti-HLA antibodies revealed
      that antigen presentation to all M. tuberculosis reactive T cell clones was
      restricted by HLA-DR3 molecules. We have thereby demonstrated the presence of
      human T cell specificities directed against the mycobacterial HSP70 antigen that
      are able to discriminate between M. tuberculosis and M. leprae.

PMID- 9544783
TI  - Antifungal antibiotic hamycin increases susceptibility of Candida albicans to
      phagocytosis by murine macrophages.
AB  - Hamycin is an antifungal antibiotic produced by Streptomyces pimprina Thirum. In
      the present study, the effect of hamycin on (a) the phagocytosis of Candida
      albicans by murine peritoneal macrophages and (b) the cell surface hydrophobicity
      (CSH) of C. albicans was investigated. Addition of hamycin to the culture of
      macrophages and Candida cells increased the susceptibility of Candida cells to
      the phagocytosis by macrophages. Pretreatment of Candida cells with hamycin
      increased their vulnerability to killing by macrophages. Examination of physico
      chemical properties of Candida cell surface showed a significant decrease in the
      CSH. These findings suggest that the binding of hamycin to Candida cells induces
      biochemical/physico-chemical alterations of the surface, so that it becomes more
      susceptible to phagocytosis by murine macrophages.

PMID- 9544784
TI  - Neuropeptides in the livers of mice during bacterial infections.
AB  - Neuropeptides such as substance P (SP) and vasoactive intestinal peptide (VIP)
      are known to act as immunomodulators. We investigated the induction of SP and VIP
      in the livers of mice infected with Listeria monocytogenes or injected with
      Tsukamurella paurometabolum. VIP was detected in the livers of mice after L.
      monocytogenes infection by an immunohistochemical technique and preproVIP mRNA,
      which was detected by reverse transcription-polymerase chain reaction (PCR), was
      induced post infection. However, no SP was detected. In contrast, SP, but not VIP
      was detected within granulomas in the livers of T. paurometabolum-injected mice,
      suggesting VIP and SP might be selectively induced in the liver by different
      bacterial infections.

PMID- 9544785
TI  - Genotypic and phenotypic characterization of two Swedish isolates and two
      prototypic strains of Coxiella burnetii.
AB  - Two Swedish isolates of Coxiella burnetii and the two prototype strains of the
      species, Nine Mile and Priscilla, were characterized with regard to their
      multiplication and cytopathic effect on BGM cells and by PCR-based amplification
      of repetitive element DNA and the C. burnetii-specific plasmids QpH1 and QpRS.
      Moreover, 1330 bp of each 16S rRNA gene were sequence-determined. All four
      strains multiplied at virtually the same rate and displayed the same type of
      vacuoles in the BGM cells. Genetic homogeneity was observed inasmuch as the 16S
      rDNA sequences were identical and the strains showed identical PCR amplification
      patterns using primers specific to enterobacterial repetitive intragenic
      consensus DNA sequences. The two Swedish strains and the Priscilla strain also
      showed identical patterns after PCR amplification of repetitive extragenic
      palindromic DNA sequences, whereas the Nine Mile strain demonstrated a similar,
      but not identical pattern. Thus, the investigated strains demonstrated very
      similar phenotypic and genotypic characteristics. This finding is discussed in
      view of the very rare occurrence of domestic Q fever in Sweden.

PMID- 9544786
TI  - New visions in the pharmacology of anticonvulsion.
AB  - Seizures are resistant to treatment with currently available anticonvulsant drugs
      in about 1 out of 3 patients with epilepsy. Thus, there is a need for new, more
      effective anticonvulsant drugs for intractable epilepsy. Furthermore, because of
      the inadequacy of the currently available anticonvulsant armamentarium with
      respect to safety, newly developed drugs should be less toxic than existing
      drugs. Previous and current strategies for development of novel anticonvulsants
      with improved efficacy or safety are critically discussed in this review. 'Old
      drugs' (or 'first generation' drugs), which were developed and introduced between
      1910 and 1970, are compared with new anticonvulsants both in terms of clinical
      efficacy and safety and in terms of mechanisms of action. The new drugs are
      referred to as 'second generation' drugs, i.e. anticonvulsants which have been
      introduced into clinical practice in recent years, or 'third generation' drugs,
      i.e. compounds in the pipeline of development. In spite of some 30 years of
      'modern' neuroscientific epilepsy research, most novel, clinically effective
      second generation anticonvulsants have been found by screening (i.e. serendipity)
      or structural variation of known drugs and not by rational strategies based on
      knowledge of processes involved in generation of seizures or in development of
      epilepsy. An exception are only the GABA (gamma-aminobutyrate)-mimetic drugs
      vigabatrin and tiagabine and, to some extent, gabapentin, which have been
      developed by a rational strategy, i.e. the 'GABA hypothesis' of epilepsy. The
      fact that preclinical seizure models used for identification and development of
      novel drugs have been originally validated by old drugs, i.e. conventional
      anticonvulsants, may explain that several of the new drugs possess mechanisms
      which do not differ from those of the standard drugs. This may also explain that
      none of the new drugs seems to offer any marked advantage towards the old, first
      generation drugs with respect to the ultimate goal of drug treatment of epilepsy,
      i.e. complete control of seizures, although some of the second generation drugs
      may have benefits in terms of side effects and tolerability. It is to be hoped
      that the various novel currently used or planned strategies for drug development
      produce more effective and safe anticonvulsants than previous strategies. This
      goal can only be achieved by strengthening our understanding of the fundamental
      pathophysiology of seizure expression and epileptogenesis as theoretical
      substrates for new pharmacological strategies, and by devising and refining
      laboratory models for studying new agents obtained by such strategies.

PMID- 9544787
TI  - Tetrahydroaminoacridine and D-cycloserine stimulate acquisition of water maze
      spatial navigation in aged rats.
AB  - We investigated the effect of tetrahydroaminoacridine, a cholinesterase inhibitor
      and D-cycloserine (a partial glycine-B agonist of the NMDA receptor complex) on
      the defect of water maze spatial navigation in rats induced by aging.
      Tetrahydroaminoacridine (3 mg/kg, i.p.) or D-cycloserine (10 mg/kg, i.p.)
      enhanced acquisition of the water maze task. A combination of subthreshold doses
      of tetrahydroaminoacridine (1 mg/kg) and D-cycloserine (3 mg/kg) improved water
      maze acquisition, but a combination of lower subthreshold doses
      (tetrahydroaminoacridine 0.3 mg/kg + D-cycloserine 1 mg/kg) was ineffective.
      Consolidation in water maze test was not improved by tetrahydroaminoacridine (3
      mg/kg) and/or D-cycloserine (10 mg/kg). The results suggest that
      tetrahydroaminoacridine and D-cycloserine synergistically enhance acquisition of
      spatial navigation in aged rats.

PMID- 9544788
TI  - The anxiolytic effect of gamma-hydroxybutyrate in the elevated plus maze is
      reversed by the benzodiazepine receptor antagonist, flumazenil.
AB  - The effects of gamma-hydroxybutyrate (GHB), a product of gamma-aminobutyric acid
      (GABA) metabolism which possesses neuromodulatory properties in brain, were
      investigated in the elevated plus maze in rats. The number of entries and the
      time spent in the open arms of the maze were increased by GHB (50, 150, 250 mg/kg
      i.p.). This is classically considered as indicative of an anxiolytic effect of
      the drug. There was no sedative effect at these doses as measured by the
      spontaneous locomotor activity in the actimeter or the total number of arm
      entries. The anxiolytic properties of GHB were reversed by neither the GHB
      receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5(H)-5-olylidene acetic acid)
      (300 mg/kg i.p.), nor the opioid receptor antagonist, naloxone (10 mg/kg i.p.).
      However the anti-anxiety effect of GHB was antagonized by the benzodiazepine
      receptor antagonist, flumazenil (10 mg/kg i.p.), suggesting an interaction of GHB
      with the GABA(A) receptor complex which mediates the anti-anxiety effect of
      benzodiazepines.

PMID- 9544789
TI  - Chronic exposure to melatonin receptor agonists does not alter their effects on
      suprachiasmatic nucleus neurons.
AB  - Previous studies have demonstrated that melatonin and a novel melatonin receptor
      agonist, S20098 (N-[2-(7-methoxy-1-naphthyl) ethyl] acetamide), regulate neuronal
      firing activity of photically responsive cells in the suprachiasmatic nucleus in
      vivo. In the present study, we used several different methods to investigate the
      effects of chronic daily treatment with melatonin, S20098 (1.0 mg/kg, s.c.) or
      control vehicle for 14 d on responsiveness of suprachiasmatic nucleus cells to
      these agonists. Both chronic and acute application of drugs were carried out
      during the day-night transition period. We confirmed that suprachiasmatic nucleus
      cells from control animals were most sensitive at this circadian phase. Chronic
      drug treatments did not alter sensitivity of photically responsive
      suprachiasmatic nucleus cells to S20098 or melatonin given intraperitoneally
      (i.p.) or iontophoretically in vivo. Suprachiasmatic nucleus cells studied in
      brain slice preparations also responded similarly to micropressure ejections of
      melatonin receptor agonists regardless of drug pretreatment. These results
      indicate that chronic melatonin receptor agonist pretreatment does not result in
      desensitization of suprachiasmatic nucleus neuronal responses to these agonists
      during the daily phase of maximum melatonin sensitivity.

PMID- 9544790
TI  - Weak anticonvulsant effects of two novel glycineB receptor antagonists in the
      amygdala-kindling model in rats.
AB  - In the present work we evaluated the anticonvulsant effects of two novel
      antagonists of the glycine co-agonist site (glycineB receptor) within the N
      methyl-D-aspartate (NMDA) receptor complex, MRZ 2/576 (a tricyclic pyrido
      phtalazin dione derivative) and L-701,324 (7-chloro-4-hydroxy-3-(3-phenoxy)phenyl
      2(H)quinoline). As a model of epilepsy we used amygdala-kindled rats, which are
      considered as a model to study the efficacy of drugs against human complex
      partial seizures. MRZ 2/576 (2.5-10 mg/kg i.p. 15 min before testing) did not
      influence afterdischarge threshold, which is believed to be the most subtle
      indicator of efficacy against kindled seizures, nor did it affect other measures
      of seizure activity such as seizure severity, seizure duration and afterdischarge
      duration. However, MRZ 2/576 produced dose-dependent ataxia as measured in the
      open field and rotarod test. The highest dose tested (10 mg/kg) also markedly
      reduced rectal temperature (by about 1.5 degrees C). L-701,324 (2.5-10 mg/kg i.p.
      30 min before testing) dose dependently and significantly increased
      afterdischarge threshold, but other seizure parameters remained unchanged. The
      ataxia produced by lower doses of L-701,324 (2.5 and 5 mg/kg) was more pronounced
      than that caused by MRZ 2/576. However, the ataxia observed following the higher
      dose of L-701,324 (10 mg/kg) was less intense than that elicited by MRZ 2/576.
      The behavioral alterations produced by the two drugs did not resemble those
      characteristic for classical competitive and uncompetitive NMDA receptor
      antagonists. In conclusion, our data indicate that glycineB receptor antagonists
      are not promising candidates for the treatment of complex partial seizures in
      humans, at least as monotherapy.

PMID- 9544791
TI  - Increase in nitric oxide in the hypoxic-ischemic neonatal rat brain and
      suppression by 7-nitroindazole and aminoguanidine.
AB  - We measured the changes in nitric oxide (NO) metabolites in the brains of
      neonatal rats with hypoxic-ischemic damage. There were two peaks of NO
      metabolites in the lesioned side of the cortex without treatment: one during
      hypoxia and the other during the re-oxygenation period. Prehypoxic treatment with
      7-nitroindazole, a selective neuronal NO synthase inhibitor, suppressed both
      peaks of NO metabolites, whereas prehypoxic treatment with aminoguanidine, a
      selective inducible NO synthase inhibitor, partially suppressed only the peak in
      the re-oxygenation period. These data suggest different roles of neuronal and
      inducible NO synthases in the pathogenesis of hypoxic-ischemic encephalopathy.

PMID- 9544792
TI  - Effects of imipramine and sertraline on protein kinase activity in rat frontal
      cortex.
AB  - Three-week administration of sertraline or imipramine to rats (10 mg/kg,
      intraperitoneally, twice a day) increased ex vivo cyclic AMP-dependent protein
      kinase activity in the soluble but not in the particulate fraction of the frontal
      cortex. However, cyclic AMP-dependent protein kinase activity was not affected in
      either fraction of the parietotemporal cortex and hippocampus. Neither
      antidepressant altered protein kinase C activity in the soluble and particulate
      fractions or Ca2+/calmodulin-dependent protein kinase II activity in the frontal
      cortex. Therefore, sertraline and imipramine both selectively enhance cyclic AMP
      dependent protein kinase activity in the frontal cortex. This enhancement might
      be involved in their biochemical mechanisms.

PMID- 9544793
TI  - Activation of genes for growth factors and cyclooxygenases in rat gastric mucosa
      during recovery from stress damage.
AB  - Growth factors and prostaglandins protect the gastric mucosa against stress
      induced lesions but their role in the recovery of the mucosa from these lesions
      has been little studied. We evaluated gastric mucosa lesions, gastric blood flow,
      mucosal generation of prostaglandin E2 and mucosal gene expression of epidermal
      growth factor (EGF) and transforming growth factor alpha (TGF alpha) as well as
      constitutive prostaglandin cyclooxygenase-1 and inducible cyclooxygenase-2 and
      the effect of the inhibition of these enzymes on the recovery of mucosa from the
      stress-induced lesions. Rats were exposed to 3.5 h of water immersion and
      restraint stress and killed at 0, 2, 4, 6, 8, 12 and 24 h after stress. The
      number of gastric lesions was determined and gastric blood flow was measured by
      H2-gas clearance. Gastric acid secretion was tested in separate gastric fistula
      rats. Gastric mucosa biopsies were taken for determination of immunoreactive EGF
      and TGF alpha. Expression of EGF and TGF alpha mRNA and cyclooxygenase-1 and
      cyclooxygenase-2 mRNA was also determined by reverse-transcriptase polymerase
      chain reaction. The number of gastric lesions induced by 3.5 h stress averaged
      approximately 20 per rat and declined significantly at 2, 4, 6, 8 and 12 h, to
      disappear almost completely after 24 h. This was accompanied by a gradual rise in
      gastric blood flow, mucosal generation of prostaglandin E2 and mucosal EGF and
      TGF alpha contents, while the increased gastric acid secretion returned to
      normal. In the intact mucosa, EGF mRNA was not detected but TGF alpha mRNA was
      found in measurable amounts. Following exposure to stress, the expression of both
      these factors was significantly increased. Similarly, the expression of cyclo
      oxygenase-1 and cyclooxygenase-2 mRNA was detected in the oxyntic mucosa at all
      time intervals after exposure to stress. Indomethacin (5 mg/kg i.p.), an
      inhibitor of cyclooxygenase-1 and cyclooxygenase-2, and meloxicam (1 mg/kg i.p.),
      an inhibitor of cyclooxygenase-2, both prolonged the healing of stress lesions
      and reduced the gastric blood flow, while enhancing gastric acid secretion at all
      times tested. We conclude that healing of stress lesions results in the
      restoration gastric blood flow and mucosal prostaglandin generation and that
      these effects are accompanied by overexpression of EGF and TGF alpha as well as
      cyclooxygenase-1 and cyclooxygenase-2 mRNA and by increased biosynthesis of
      gastroprotective prostaglandin.

PMID- 9544794
TI  - Protective effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose)
      synthase in a carrageenan-induced model of local inflammation.
AB  - A cytotoxic cycle triggered by oxidant-induced DNA single strand breakage and
      subsequent activation of the nuclear enzyme poly (ADP-ribose) synthetase have
      been shown to contribute to the cellular injury during various forms of oxidant
      stress in vitro. The aim of the present study was to investigate the role of poly
      (ADP-ribose) synthetase in a model of acute local inflammation (carrageenan
      induced pleurisy), where oxyradicals, nitric oxide and peroxynitrite are known to
      play a crucial role in the inflammatory process. The results show that the poly
      (ADP-ribose) synthetase inhibitor 3-aminobenzamide (given at 1-30 mg/kg) inhibits
      the inflammatory response (pleural exudate formation, mononuclear cell
      infiltration, histological injury). Moreover, 3-aminobenzamide reduces the
      formation of nitrotyrosine, an indicator of the formation of peroxynitrite, in
      the lung. The present results demonstrate that 3-aminobenzamide, presumably by
      inhibition of poly (ADP-ribose) synthetase, exerts potent anti-inflammatory
      effects. Part of the anti-inflammatory effects of 3-aminobenzamide may be related
      to a reduction of neutrophil recruitment into the inflammatory site.

PMID- 9544795
TI  - Nitrosative and oxidative stress induced heme oxygenase-1 accumulation in rat
      mesangial cells.
AB  - The formation of nitric oxide (NO.) and superoxide (O2-) promotes rat mesangial
      cell death. Apoptotic death is characterized by DNA fragmentation, caspase-3
      activation and concomitant poly(ADPribose) polymerase cleavage, as well as
      accumulation of the tumor suppressor protein p53. In close association with
      apoptotic parameters we noticed upregulation of heme oxygenase by the NO donor S
      nitrosoglutathione (GSNO) and the redox cycler 2,3-dimethoxy-1,4-naphthoquinone
      (DMNQ) in a time- and concentration-dependent manner. In response to the NO.
      donor, heme oxygenase-1 expression was more easily obtained than initiation of
      apoptosis. Radical (NO./O2-) cogeneration abrogated DNA fragmentation, suppressed
      caspase activation and lowered p53 accumulation, thereby promoting cell survival
      of mesangial cells. In contrast, heme oxygenase-1 expression remained elevated
      under conditions of GSNO/DMNQ coadministration. Conclusively, heme oxygenase-1 is
      a stress marker for both nitrosative and oxidative stress. Accumulation of heme
      oxygenase-1 is found under conditions of both, apoptotic cell death and cell
      survival, thereby questioning a specific cytoprotective role of heme oxygenase-1
      under conditions of NO. and/or O2- formation in rat mesangial cells.

PMID- 9544796
TI  - Differential alpha1-adrenoceptor labeling by [3H]prazosin and [3H]tamsulosin.
AB  - The radioligand binding properties of [3H]prazosin and [3H]tamsulosin at alpha1
      adrenoceptors of several rat tissues, human prostate and cloned rat and human
      alpha1-adrenoceptor subtypes were compared in Tris/EDTA buffer unless otherwise
      indicated. The affinity of [3H]tamsulosin at tissue and cloned alpha1A- and
      alpha1B-adrenoceptors was somewhat greater and smaller, respectively, than that
      of [3H]prazosin. In most rat tissues and at cloned rat alpha1A- and alpha1B
      adrenoceptors, [3H]tamsulosin had a smaller Bmax than [3H]prazosin. Studies with
      rat liver showed that this was due to considerably poorer labeling of agonist low
      affinity sites, while both radioligands detected similar numbers of agonist high
      affinity sites. Statistically significant differences in the number of binding
      sites for both ligands were not detected in HEPES or glycylglycine buffer, as the
      detectable receptor number for [3H]prazosin and [3H]tamsulosin tended to be
      smaller and greater, respectively, in these than in Tris/EDTA buffer. Among human
      alpha1-adrenoceptor subtypes [3H]tamsulosin labeled fewer sites than [3H]prazosin
      for alpha1B- but more sites for alpha1A- and alpha1D-adrenoceptors. We conclude
      that [3H]prazosin and [3H]tamsulosin do not detect the same number of alpha1
      adrenoceptors under a variety of conditions. This should be taken into account in
      the interpretation of data obtained with either radioligand.

PMID- 9544797
TI  - Effects of bisaramil, a novel class I antiarrhythmic agent, on heart, skeletal
      muscle and brain Na+ channels.
AB  - The effects of bisaramil, a novel diazabicyclononane antiarrhythmic agent, were
      compared to those of lidocaine, a clinically used class Ib antiarrhythmic agent,
      on heart, skeletal muscle and brain Na+ channels expressed in Xenopus laevis
      oocytes using a two-electrode voltage clamp. Both bisaramil and lidocaine
      produced a concentration-dependent tonic block of Na+ current that was most
      effective on cardiac channels, but bisaramil was more potent than lidocaine. Both
      drugs produced a concentration-dependent shift in the voltage-dependence of
      inactivation and delayed recovery from inactivation. Bisaramil produced marked
      frequency-dependent block of heart channels and mild frequency-dependent block of
      skeletal muscle and brain channels, whereas lidocaine produced marked frequency
      dependent block of all three channel types. Therefore, bisaramil shows tonic and
      frequency-dependent blockade that is most potent against the heart Na+ channel,
      which may account for its potent antiarrhythmic efficacy in vivo, and may result
      in reduced central nervous system toxicity compared to clinically used agents
      such as lidocaine.

PMID- 9544798
TI  - Effect of SA4503, a novel sigma1 receptor agonist, against glutamate
      neurotoxicity in cultured rat retinal neurons.
AB  - We examined the effects of sigma1 receptor agonists against glutamate-induced
      neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal
      rat retinas (16-19 d gestation) were used. The neurotoxic effect of glutamate was
      quantitatively assessed using the trypan blue exclusion method. A brief exposure
      of retinal cultures to glutamate (500 microM) led to delayed neuronal cell death.
      The glutamate-induced neurotoxicity was inhibited by (5R,10S)-(+)-5-methyl-10,11
      dihydro-5H-dibenzo-[a,b]-cyclohepten-5 ,10-imine hydrogen maleate (MK-801). The
      sigma1 receptor agonists, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)
      piperazine dihydrochloride (SA4503) and (+)-pentazocine at a concentration range
      of 0.1 approximately 100 microM reduced the glutamate-induced neurotoxicity in a
      dose-dependent manner. In addition, the neuroprotective effects of both SA4503
      and (+)-pentazocine were antagonized by co-treatment with N,N-dipropyl-2-[4
      methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a
      putative sigma1 receptor antagonist. These findings suggest that sigma1 receptor
      agonists protect retinal cells against glutamate-induced neurotoxicity.

PMID- 9544799
TI  - Clotrimazole and bifonazole detach hexokinase from mitochondria of melanoma
      cells.
AB  - Cancer cells are characterized by a high rate of glycolysis. Hexokinase (ATP: D
      hexose 6-phosphotransferase, EC 2.7.1.1), the only glycolytic enzyme which binds
      to mitochondria, is exceptionally high in cancer cells, and believed to play a
      key role in regulating cell energy metabolism and cancer cell growth rate. We
      have previously found that clotrimazole (1-(alpha-2-chlorotrityl)imidazole) and
      bifonazole (1-(alpha-biphenyl-4-ylbenzyl)imidazole), the antifungal azole
      derivatives, which were recently recognized as calmodulin antagonists, are
      calmodulin antagonists which most effectively reduce glycolysis and ATP level in
      B16 melanoma cells. They act through allosteric regulation and detachment of
      glycolytic enzymes from cytoskeleton. Here we report of a novel, additional,
      mechanism of action of these drugs. We show that they induce a dose-dependent
      detachment of hexokinase from mitochondria of B16 melanoma cells. This effect
      preceded the decrease in cell viability. These results suggest that clotrimazole
      and bifonazole may be promising drugs in treatment of melanoma.

PMID- 9544800
TI  - Ca2+ release-activated channels in rat stomach smooth muscle cells.
AB  - In rat stomach fundus, contractions induced by Ca2+ (1.8 mM) were strikingly
      potentiated by thapsigargin. This potentiation was partially inhibited by the
      blockers of Ca2+ release activated channels (CRACs), miconazole and SK&F96365 ([1
      [beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole, HCL]) and
      slightly blocked by the antagonist of calcium voltage-operated channels (VOCs),
      isradipine. In dissociated cells in a 0Ca solution, thapsigargin potentiated the
      increase in intracellular calcium after reintroduction of Ca2+. This potentiation
      was partially reduced by the CRAC blockers, but not by the VOC blockers. This
      data suggests that calcium influx increased due to the depletion of intracellular
      calcium by thapsigargin and that this influx occurs predominantly through CRACs.

PMID- 9544801
TI  - Specific G protein activation and mu-opioid receptor internalization caused by
      morphine, DAMGO and endomorphin I.
AB  - Previous studies have shown that the agonist [D-Ala2, N-Me-Phe4, Gly
      ol5]enkephalin (DAMGO) but not morphine induces mu-opioid receptor
      internalization [Arden, J.R., Segredo, V., Wang, Z., Lameh, J., Sadee, W., 1995.
      J. Neurochem. 65, 1636-1645]. In the present study we investigated the
      relationship between internalization of the mu-opioid receptor and the specific G
      proteins activated following treatment with morphine, DAMGO and endomorphin I
      (Tyr-Pro-Trp-Phe-NH2) (a putative endogenous mu-opioid receptor agonist) in human
      embryonic kidney (HEK) cells. Endomorphin I and DAMGO, but not morphine, caused
      mu-opioid receptor internalization. Morphine, DAMGO and endomorphin I each
      activated Gi1 alpha/Gi2 alpha, Go alpha and Gi3 alpha to a similar extent, but
      not Gq alpha/G11 alpha or Gs alpha in HEK membranes. Therefore, the three ligands
      tested differed in their ability to internalize mu-opioid receptors even though
      they were similar in activating individual G proteins.

PMID- 9544802
TI  - Capillary electrophoretic behavior of milk proteins in the presence of non-ionic
      surfactants.
AB  - The electrophoretic behavior of alpha-lactalbumin and beta-lactoglobulins (A and
      B) in the presence of non-ionic surfactants was studied by capillary
      electrophoresis (CE), using a poly(ethylene glycol) coated capillary column. The
      surfactants (Tween 20, Brij 35 and 78) were used as buffer additives. The
      separation is based on the difference in the strength of protein-surfactant
      association complexes, which results in a change of the effective electrophoretic
      mobility. The modification of the electrophoretic mobilities of proteins was
      observed and this variation permitted the estimation of the interaction between
      protein and surfactant. The effect of surfactant type and concentration on the
      migration behavior of protein in CE is discussed. It is found that the retention
      behavior of the milk proteins (the alpha-lactalbumin and the beta-lactoglobulins)
      in CE is very different. The pH of the buffer and the surfactant type influence
      significantly the protein-surfactant interactions.

PMID- 9544803
TI  - Characterization and application of new macroporous membrane ion exchangers.
AB  - A new ready-to-use unit for high-performance membrane chromatography has been
      characterized. Its dynamic capacity, resolving power and protein recovery were
      measured at different flow-rates. The binding capacity was 0.5-2 mg/cm2 with a
      95% recovery at 10 ml/min irrespective of the protein concentration up to 10
      mg/ml. For very-high flow-rates (50 and 100 ml/min) the recovery was 90% and 70%.
      At these flow-rates, the maximum back-pressure was about 0.1 MPa and was
      independent of the filtration area. By increasing the filtration area, a
      proportional capacity increase was obtained, indicating an easy scale-up. High
      flow-rates had only a slight effect on resolution. This new adsorber was able to
      purify IgM from supernatant of cell culture of a human hybridoma in less than 8
      min with a high degree of purity (95%).

PMID- 9544804
TI  - Physico-chemical characterization of proteins by capillary electrophoresis.
AB  - The electrophoretic mobility of proteins was successfully determined by means of
      capillary electrophoresis (CE) with various background electrolytes (BGEs). The
      objective was focused on the variation in BGE physico-chemical composition and
      the consequential impact on the observed protein charge. Experimental and
      calculated mobilities, according to Henry's equation, versus ionic strength have
      been compared. For positively-charged lysozyme, a good agreement between observed
      and calculated mobilities was observed using triethanolamine chloride at pH 7.0
      as the BGE. Mobility close to zero was shown using borate (pH 8.0) and phosphate
      (pH 7.0) at a low ionic strength of about 20 mmol l(-1), and as a consequence,
      specific adsorption of oxyanions was evidenced. Lysozyme retention in the case of
      reversed-phase high-performance liquid chromatography (RP-HPLC) was decreased by
      the presence of phosphate ions. CE and HPLC are complementary tools for
      characterizing the behaviour of lysozyme. On the other hand, the mobility of the
      negatively-charged alpha-lactalbumin remained constant as regards phosphate at pH
      7.0 in the 20-200 mmol l(-1) range, contrary to the decrease that had been
      expected with the increasing ionic strength. beta-Lactoglobulin exhibited
      increasingly lower mobilities than those expected of boric acid/borate at pH 7.0
      and 8.0 (I=20 mmol l(-1)).

PMID- 9544805
TI  - Influence of the nature of coupling agents on insulin adsorption on supports
      grafted with sialic acid for high-performance affinity chromatography.
AB  - Porous silica exhibits excellent mechanical properties for use as a stationary
      phase for high-performance liquid chromatography. However, negative surface
      charges make it unusable in its native state. For this reason, silica beads are
      coated with dextran polymers carrying a calculated amount of diethylaminoethyl
      groups. Both the minimization of non-specific interactions and the hydrophilic
      character of such supports allow their functionalization with biospecific ligands
      and finally their use in high-performance affinity chromatography of biological
      products. The use of these modified supports in high-performance affinity
      chromatography requires a better understanding of various characteristics of
      stationary phases. For this purpose, several techniques were utilized, in
      particular, size-exclusion chromatography and adsorption of radiolabelled
      albumin. These methods provided complementary information on the structure of
      these supports. Coated silica-based supports were functionalized with sialic acid
      by means of different coupling agents. The affinity of these supports for insulin
      was determined by the establishment of adsorption isotherms and by high
      performance affinity chromatography, to evidence the relationships between
      structural characteristics of the supports and their separation properties. The
      study of interactions between these supports and insulin allowed us to show the
      importance of the coupling method on the performances of supports in affinity
      chromatography.

PMID- 9544806
TI  - Preliminary report on fractionation of fucans by ion-exchange displacement
      centrifugal partition chromatography.
AB  - A new method combining ion-exchange displacement chromatography with centrifugal
      partition chromatography (CPC) was used for the fractionation of partially
      depolymerized fucans (polysulphated polysaccharides). The ion-exchanger was
      Amberlite LA2, a high-molecular-mass liquid secondary amine miscible with most
      common organic solvents and immiscible with aqueous solutions. Ion-exchange
      displacement centrifugal partition chromatography was performed with LA2 in
      methyl isobutyl ketone (MiBK) as the stationary phase, water as the mobile phase,
      Cl- as the carrier and OH- as the displacer. A complex mixture of partially
      depolymerized fucans was resolved into adjacent families characterized by their
      peak molecular mass and polydispersity. The Dubois test (sugar) and the azur A
      test (SO3-) confirmed the displacement mode of the process, and size-exclusion
      chromatographic controls confirmed its efficiency.

PMID- 9544807
TI  - High-performance affinity chromatography for the purification of heparin-binding
      proteins from detergent-solubilized smooth muscle cell membranes.
AB  - Heparin and heparan sulfates are regulators of cellular events including
      adhesion, proliferation and migration. In particular, the antiproliferative
      effect of heparin on smooth muscle cell (SMC) growth is well described. However,
      its mechanism of action remains unclear. Numerous results suggest an endocytosis
      mediated by a still unknown heparin receptor on vascular SMCs. In order to
      identify a putative heparin receptor on SMCs that could be involved in heparin
      signalling, affinity chromatography supports were developed. In this paper, we
      describe high-performance liquid affinity chromatography (HPLAC) supports
      obtained from silica beads coated with dextran polymer substituted by a
      calculated amount of diethylaminoethyl functions. With a polysaccharide dextran
      layer, this type of support can be grafted with specific ligands, such as
      heparin, using conventional coupling methods. In a previous work, we
      demonstrated, using butanedioldiglycidyl ether, that silica stationary phases
      coupled to heparin could be used for the fast elution and good peak resolution of
      heparin-binding proteins. In the present work, an affinity chromatographic
      fraction of SMC membrane extracts was analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and six heparin-binding proteins
      from dodecyloctaethyleneglycol monoether-solubilized SMCs were observed. Their Mr
      values were between 40 and 70 kDa, with three major protein bands at 66, 45 and
      41 kDa. These results indicate the usefulness of the chromatographic method for
      purifying heparin binding proteins from SMC membrane.

PMID- 9544808
TI  - Purification of a 41 kDa cod-allergenic protein.
AB  - Cod fish is one of the foods most frequently involved in allergy. Only the cod
      allergen Gad c I, a 12.3 kDa parvalbumin, has been purified and characterized.
      Recently, we have detected allergen bands which have not previously been
      described, in particular a 41 kDa protein, by Western-blot. In the present work,
      this protein has been purified from a crude cod extract by ammonium sulfate
      fractionation, hydroxyapatite chromatography and preparative electrophoresis; a
      single band with an Mr of 41 x 10(3) was found in silver-stained sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The amino acid composition and the
      isoelectric point of the protein were determined. The purified protein (p41) was
      shown to bind specifically to reaginic IgE from sera of cod-allergic individuals
      and to a monoclonal anti-parvalbumin which recognizes specifically the first
      calcium binding site of parvalbumins. p41 may therefore contain a calcium binding
      site corresponding to an IgE-epitope similar to that of Gad c I.

PMID- 9544809
TI  - Capillary zone electrophoresis in normal or reverse polarity separation modes for
      the analysis of hydroxy acid oligomers in neutral phosphate buffer.
AB  - Capillary zone electrophoresis (CZE) with neutral phosphate buffer as the
      background electrolyte was used to analyse water-soluble oligomers obtained by
      polycondensation of racemic lactic acid. Two CZE separation modes were tested.
      The first mode was based on normal separation (injection at the anodic side)
      using a fused-silica capillary. Eight peaks were observed within a 60-min
      migration time range. They were ascribed to dimer and higher water-soluble
      oligomers. Peaks from dimer to tetramer were split due to sensitivity for the
      fine structures at the level of the distribution of chiral lactic acid moieties
      in oligomer chains. The second mode was based on reverse separation (injection at
      the cathodic side) using a fused-silica capillary modified by adsorption of a
      polycation on its inner wall. Under these conditions, oligomers were rapidly
      separated without peak splitting. Considering the forces which are involved in
      CZE, data were plotted as a function of 1/t scale, according to the equation
      [signal]=f((-1)(k)/t) where k=0 and k=1 for normal and reverse separation modes,
      respectively. Such a plot allowed direct comparison between the various runs
      after a simple translation along the 1/t axis, regardless of the separation mode
      and the variation of electroosmotic flow. The second separation mode allowed
      separation of 3-hydroxybutyric acid and 6-hydroxyhexanoic acid oligomers. For the
      former series of oligomers, a side reaction generating crotyl bonds was observed
      due to the high sensitivity of CZE. It was shown that separation was governed by
      the ratio charge/mass of the oligoesters whatever their structure.

PMID- 9544810
TI  - Covalent chromatography of influenza virus membrane M1 protein on activated
      thiopropyl Sepharose-6B.
AB  - The M1 protein of influenza virus is a highly hydrophobic polypeptide that is
      resistant to enzyme cleavage during incubation in water solutions. We show here
      that the M1 protein that is immobilized on an insoluble activated support
      (thiopropyl Sepharose-6B) by means of a thiol-disulfide exchange reaction
      acquires sensitivity to trypsin. After tryptic digestion noncysteine-containing
      peptides of M1 were removed by washing the support, while cysteine-containing
      ones were detached from the support by reduction. As a result, 24 unique tryptic
      peptides of M1 protein were clearly separated by reversed-phase high-performance
      liquid chromatography. The described method opens a new way to the investigation
      of functional properties of distinct domains of viral thiol proteins.

PMID- 9544811
TI  - Analytical development of electrospray and nanoelectrospray mass spectrometry in
      combination with liquid chromatography for the characterization of proteins.
AB  - Mass spectrometry has significantly extended its applicability in the area of
      characterization of protein structures. Electrospray ionization enables on-line
      coupling with liquid chromatography which has become a powerful tool for the
      characterization of peptide and protein mixtures. The most recent development of
      a nanoelectrospray source, using capillary forces for a particularly mild analyte
      transport and ionization into the mass spectrometer, opens a wide field for
      applications to protein structure analysis. In this paper, the analytical
      development of liquid chromatography-electrospray ionization mass spectrometry
      and nano-electrospray ionization mass spectrometry, adapted to an electrospray
      ionization quadrupole mass spectrometer and its application to the
      characterization of noncovalent protein complexes are described.

PMID- 9544812
TI  - Isolation of the O-glycosidically linked oligosaccharides obtained by alkaline
      borohydride degradation from oviducal mucins of the toad Bufo bufo.
AB  - A combination of normal-phase high-performance liquid chromatography (HPLC) on
      amino-bonded silica and reversed-phase HPLC on octadecylsilica has been used to
      separate the reduced oligosaccharides produced by alkaline borohydride
      degradation of oviducal mucins obtained from the jelly coat of Bufo bufo. The
      former technique provides suitable separation on the basis of molecular size,
      while the latter method offers selectivity for stereoisomers. Thirty-four
      compounds, ranging in size from a trisaccharide to a dodecaoligosaccharide, have
      been isolated preparatively using a Supelcosyl LC-NH2 normal-phase column eluted
      with aqueous acetonitrile and a Zorbax ODS reversed-phase column eluted with
      water.

PMID- 9544813
TI  - Purification of a recombinant protein expressed in yeast: optimization of
      analytical and preparative chromatography.
AB  - The industrial production of recombinant proteins requires control of both
      fermentation and purification steps. For the serodiagnosis of toxoplasmosis, the
      main antigen is a membrane protein of 30 kDa (P30). The P30 gene was cloned and
      expressed in Schizosaccharomyces pombe at 0.7 microg/ml in culture medium. Batch
      fermentation was optimized by the specific choice of peptones, which enabled
      optimum growth and protein expression without reducing the efficacy of the
      purification step. Analytical purification was then carried out using cation
      exchange chromatography. For larger volumes, scaling up was performed on expanded
      mode by using a Streamline system (Pharmacia). This purification step allowed us
      to obtain a 67.5% recovery with a purification factor greater than 27-fold.
      Expanded bed adsorption technology is a convenient and effective technique for
      protein capture directly from feedstock, and the eluted fraction is ready for a
      second affinity chromatography step. This second step is performed with a yield
      of 40% and provides a final purification factor of 2000-fold.

PMID- 9544814
TI  - Qualitative and quantitative analysis of hemoglobin variants by capillary
      isoelectric focusing.
AB  - We developed two capillary isoelectric focusing (CIEF) assays, in narrow pH
      gradients, with the aim of routinely separating and quantitating normal and
      abnormal hemoglobins (Hbs): a one-step CIEF assay where residual electroosmotic
      flow mobilizes the proteins during focalization, and a two-step CIEF assay where
      focused Hbs are mobilized by low pressure by maintaining high-voltage. The
      resolution of 0.10 pH unit obtained with the one-step assay allowed the
      separation of the Hbs A, F, S and C; but Hb A2, which represents about 2-3% of
      whole Hb, could not be quantitated. The better resolution of 0.02 pH unit
      obtained with the two-step assay allowed the separation of some Hb variants of
      very close isoelectric points. The reproducibility of retention times was
      satisfactory (C.V.<5%). Moreover, in this configuration quantitation of Hb A2, Hb
      F and Hb S led to a standard deviation of less than 5%, allowing the diagnosis of
      thalassemias. The one-step assay could be useful only for the detection of
      abnormal variants, while the two-step assay could be applied to the routine
      analysis of Hbs, with quantitation of minor fractions and presumptive
      identification of variants.

PMID- 9544815
TI  - Characterization of the oligomeric behavior of a 16.5 kDa peanut oleosin by
      chromatography and electrophoresis of the iodinated form.
AB  - Oleosins are amphipathic proteins associated with oil bodies in seeds. We
      purified the major 16,500 peanut oleosin by preparative SDS-PAGE. Autoradiography
      after SDS-PAGE separation of the iodinated oleosin revealed covalently bound
      oligomers with Mr of 21,000, 33,000, 44,000 and 51,000. The strong capacity of
      these oligomers to form aggregates and to be incorporated into large-sized
      detergent micelles was demonstrated by gel permeation and isoelectric focusing. A
      50% ethanol concentration was necessary to elute the 16,500 oleosin from octyl
      groups in hydrophobic interaction chromatography showing its natural tendency to
      interact with lipid acyl chains. This oligomerization behavior in aqueous
      solution is an indirect reflection of the interactions that occur in the oil
      body.

PMID- 9544816
TI  - Methodology for vesicle permeability study by high-performance gel exclusion
      chromatography.
AB  - A methodology based on high-performance gel exclusion chromatography (HPLC-GEC)
      has been developed to perform permeability studies of vesicles. Encapsulation of
      two marker isothiocyanate fluorescein (FITC) dextrans of 4400 and 40,500
      molecular mass was used as a model system. Combination of two TSK-PW columns, one
      efficient in vesicle sizing (G6000 PW), the other in that of dextrans (G4000 PW),
      was required to achieve complete particle separation and to remove entirely the
      unentrapped dextran after encapsulation into vesicles. Coupling fluorescence and
      light scattering detection allowed to control the efficiency of the separation,
      to quantify the vesicle leakage and to follow both the integrity of the vesicles
      and changes in their size. This methodology can be applied to other fields such
      as encapsulation of water soluble compounds and drug delivery systems.

PMID- 9544817
TI  - Evaluation of coupling of cobalamin to antisense oligonucleotides by thin-layer
      and reversed-phase liquid chromatography.
AB  - We have evaluated by chromatography two strategies of oligonucleotide binding to
      vitamin B12 (cobalamin). The first one was based on a covalent linkage of
      aminooligonucleotide to carboxycobalamin in presence of 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide hydrochloride (EDC). Carboxycobalamin and EDC
      cobalamin were eluted with a retention time of 16.5 and 21.6 min, respectively,
      in RP-HPLC, while aminooligonucleotide and oligonucleotide-cobalamin were
      coeluted at 19.4 and 19.8 min. In the second strategy, avidin was coupled to both
      biotinylated oligonucleotide and vitamin B12. Aminocobalamin and biotinylated
      cobalamin had respective retention times of 13 and 15.7 min in RP-HPLC and
      respective Rf values of 0.3 and 0.8 in thin-layer chromatography. Incubation of
      avidin with biotinylated cobalamin produced, in Superose 12 gel permeation, a
      peak with a retention time of 28 min, which corresponded to avidin-biotinylated
      cobalamin as it disappeared with an excess of either biotin or biotinylated
      oligonucleotide. In conclusion, we have prepared and purified by RP-HPLC and gel
      permeation chromatography an oligonucleotide-avidin-cobalamin complex which will
      be used as a vector complex of antisense oligonucleotides.

PMID- 9544818
TI  - Effect of salt concentration gradient on separation of different types of
      specific immunoglobulins by ion-exchange chromatography on DEAE cellulose.
AB  - A three-stage process, consisting of an ammonium sulfate precipitation step,
      dialysis desalination with microporous anion-exchange Neosepta membranes and
      anion-exchange chromatography on DEAE-cellulose DE-52 was used for the isolation
      of mouse monoclonal antibodies specific against different antigens. The ascites
      fluids contained monoclonal antibodies against human IgG, against horseradish
      peroxidase and against the heavy chain of human IgM. The effect of the salt
      concentration gradient in the elution buffer was examined with the aim of
      optimizing chromatographic conditions. The quality of separation of protein zones
      was determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      under non-reducing conditions. The immunoreactivity of purified monoclonal
      antibodies was determined by enzyme-linked immunosorbent assay using a solid
      phase adsorbed antigens against which each monoclonal antibody type was directed.

PMID- 9544819
TI  - Affinity purification and characterization of recombinant human galectin-1.
AB  - Galectin-1, a polypeptidic factor that can have major effects on cell growth and
      apoptosis, was overexpressed in E. coli. This protein was purified to homogeneity
      by affinity chromatography on lactose coupled to divinylsulfone-activated
      agarose. The recombinant galectin-1 (rGAL1) was compared with the homologous
      protein purified from human brain tissue using two-dimensional electrophoresis on
      immobilized pH gradient (IPG-DALT). rGAL1 had a major isoelectric point of 5.4
      (major pI of tissular galectin-1, 5.1) and its subunit molecular mass was 14500.
      Addition of rGAL1 to Jurkat T-lymphoblastoid cells induced cell death in a
      concentration-dependent manner.

PMID- 9544820
TI  - Gastrectomy in elderly patients.

PMID- 9544821
TI  - Frequent expression of bcl-2 protein in solitary fibrous tumors.
AB  - The distinction of solitary fibrous tumors from histologically similar neoplasms
      is often difficult because they rarely occur at a variety of extrapleural sites.
      CD34 immunoreactivity has recently been recognized to be an adjunct for the
      diagnosis of solitary fibrous tumors. However, it is now known that CD34 staining
      is not entirely specific for this entity. We evaluated 23 solitary fibrous tumors
      and 54 other spindle cell tumors often considered in the differential diagnosis
      for immunoreactivity using monoclonal antibodies directed against bcl-2 protein,
      which protects cells from apoptosis and CD34. The patients with solitary fibrous
      tumors comprised 11 men and 12 women, ranging in age from 35 to 85 years (mean,
      57.6 years). Fourteen tumors arose in the pleura, four in the retroperitoneum,
      three in the superficial soft tissue and one each in the mediastinum and uterine
      cervix. Nineteen of 23 solitary fibrous tumors (83%), irrespective of tumor site,
      demonstrated diffuse cytoplasmic staining for bcl-2 protein. bcl-2
      immunoreactivity was also observed in five of seven neurofibromas (71%), eight of
      10 synovial sarcomas (80%) and one of three spindle cell lipomas (33%). CD34
      immunoreactivity was present in all but one solitary fibrous tumor (96%), seven
      of seven neurofibromas (100%), three of three spindle cell lipomas (100%), five
      of five dermatofibrosarcomas (100%), three of three hemangiopericytomas (100%)
      and two of seven malignant fibrous histiocytomas (29%). To date, most of the
      pleural and extrapleural cases have not shown aggressive features. We suggest
      that bcl-2 protein can be used together with CD34 in the diagnosis of solitary
      fibrous tumor to distinguish this entity from other spindle cell neoplasms.

PMID- 9544822
TI  - Determination of cytosol c-erbB-2 protein in breast cancer by sandwich enzyme
      immunoassay.
AB  - We determined cytosol c-erbB-2 protein levels using a sandwich enzyme immunoassay
      in benign breast disease and primary and recurrent breast cancer and analyzed the
      relationship between c-erbB-2 protein levels and clinicopathological factors.
      Overexpression of c-erbB-2 protein, the cut-off value being set at 18 ng/mg
      protein, was observed in 26 of the 139 cases of stages I-IIIB breast cancer
      (18.7%), four of the 12 cases of stage IV breast cancer (33.3%) and seven of the
      13 recurrent breast cancer cases (53.8%). The levels of c-erbB-2 protein were
      significantly different between the stages. Overexpression of c-erbB-2 protein in
      stages I-IIIB breast cancer was associated with histological grade and serum CEA
      level, but not with other clinicopathological factors. In addition, there was an
      inverse correlation in the group of stages I-III plus IV breast cancer between c
      erbB-2 protein expression and estrogen receptor status. Overexpression of c-erbB
      2 protein can be easily determined in the cytosol fraction together with hormonal
      receptor by this method. The prognostic importance will be evaluated in ongoing
      adjuvant trials for operable breast cancer patients.

PMID- 9544823
TI  - CD4- and TCRalphabeta-positive T lymphocytes predominantly infiltrated into well
      moderately differentiated colon adenocarcinoma tissues.
AB  - Intraepithelial T lymphocytes have been reported as being functional in the
      growth of epithelial cells and also in the discrimination of aberrant cells,
      whereas their function against colon adenocarcinoma cells is obscure. The
      phenotype of colon intraepithelial T lymphocytes has been found in patients with
      inflammatory bowel diseases but not in patients with colon adenocarcinoma. In
      this study, we investigated cell surface markers of tumor-infiltrating T
      lymphocytes of adenocarcinoma of the colon and rectum at various grades of
      differentiation and intraepithelial T lymphocytes of adjacent normal colon by
      enzyme immunostaining. Among intraepithelial T lymphocytes of the normal colon,
      CD8-and TCRgammadelta-positive T lymphocytes were predominant as described. In
      contrast, tumor-infiltrating T lymphocytes of well-moderately differentiated
      adenocarcinoma of the colon and rectum were predominantly CD4- and TCRalphabeta
      positive. The decrease of TCRgammadelta-positive T lymphocytes and the increase
      of CD4 and TCRalphabeta-positive T lymphocytes in adenocarcinoma tissues of the
      colon and rectum suggests that an alteration of the local immune system
      participates in the formation of adenoma and/or adenocarcinoma of the colon and
      rectum, resulting in infiltration of CD4-positive T lymphocytes that have certain
      activity against transformed cells.

PMID- 9544824
TI  - Gastrointestinal cancer metastasis and lymphogenous spread: viewpoint of animal
      models of lymphatic obstruction.
AB  - Primary gastrointestinal cancer frequently spreads to the mesentery, omentum and
      other parts of the peritoneum and these deposits are generally considered to be
      induced by intraperitoneal seeding from the primary lesion. In this work, we
      examined the spread of gastrointestinal cancer from the viewpoint of lymphogenous
      metastasis using a rat model of mesenteric lymph vessel obstruction. With these
      models, we carried out mesenteric lymphangiography on the fourth and sixth
      postoperative days (five animals each) to examine morphological changes in the
      lymph vessels and lymph flow. In model animals with mesenteric lymph vessel
      obstruction, re-celiotomy, performed on the fourth postoperative day, revealed
      marked mesenteric edema and enlargement of the mesenteric lymph nodes, suggestive
      of lymph retention. We also carried out mesenteric lymphangiography and obtained
      images of extensive mesenteric lymph vessels and reflux of lymph distal to the
      obstruction point in all five animals. On the sixth postoperative day, we
      obtained lymphangiographic images of lymphatico-venous communication in the
      mesentery in all five animals. Thus in animals with lymph vessel obstruction, the
      lymph flow appeared to change to lymphatico-venous communication or reverse
      lateral flow. In clinical cases, it is conceivable that lymph retention and
      reflux of lymph induced by lymph vessel obstruction sometimes play a role in the
      mechanism of intraperitoneal cancer dissemination and hematogenous metastasis.

PMID- 9544825
TI  - Usefulness of magnetic resonance imaging with dynamic contrast enhancement and
      fat suppression in detecting a pancreatic tumor.
AB  - The purpose of this study was to compare the value of dynamic magnetic resonance
      imaging (MRI) and fat suppression in detecting a pancreatic tumor. The subjects
      were 19 patients with invasive ductal adenocarcinoma and six patients with islet
      cell tumor where diagnosis was established pathologically. Breath-hold gradient
      echo images, breath-hold gradient echo images with fat suppression and breath
      hold gradient echo images with dynamic enhancement at 1.5 T were obtained for all
      patients. The efficacies of these three imaging techniques were compared by
      calculating the contrast-to-noise ratio, as indicative of conspicuousness between
      a tumor-affected and a normal pancreas. As for adenocarcinoma, our results
      indicated that the usefulness in detecting the tumor was high, decreasing in the
      order dynamic contrast images > fat suppression images > plain images, and that
      the difference between any two of these three types of image was statistically
      significant. On the other hand, these imaging techniques showed no statistically
      significant difference in detecting islet cell tumors. In conclusion, dynamic MRI
      is the best method for detecting pancreatic adenocarcinoma. As the fat
      suppression technique has the advantage of being non-invasive, this method is
      suitable for screening studies of pancreatic adenocarcinoma. However, no
      advantage was recognized in using the fat suppression technique for detecting an
      islet cell tumor in comparison with plain MRI.

PMID- 9544826
TI  - The outcome of surgical treatment for gastric carcinoma in the elderly.
AB  - Surgeons are increasingly being faced with the problem of treating elderly
      gastric carcinoma patients. The purpose of this study was to elucidate the
      feasibility of surgical treatment for these patients. Among 4740 gastric
      carcinoma patients treated from 1971 to 1990, 112 (2.4%) were aged 80 or over.
      The results of treatment in this elderly group were compared retrospectively with
      those in 2664 younger gastric carcinoma patients (aged 50-69, control group,
      56.2%). The TNM stage distribution and the curative resection rates (75.9 vs
      81.4%) were similar between the groups. Reduced nodal dissection was more common
      in the elderly group. The elderly had a higher incidence of preoperative risk
      factors (76.8 vs 53.1%) and 90-day mortality (10.7 vs 3.9%). However, the
      postoperative complication rates were similar between the groups. The 90-day
      mortality rates in the elderly group were higher in the subgroups undergoing
      total gastrectomy or D2 dissection. In the patients without pre-existing
      morbidity, the 30-day mortality, 90-day mortality and postoperative complications
      were similar between the groups. The 5-year survival rate after curative
      resection of the elderly group was significantly lower than that of the control
      group (44.4 vs 74.0%). This difference lost significance when non-cancer death
      was excluded (62.5 vs 79.9%). We believe that, although gastrectomy can be
      carried out safely in elderly patients, extended surgery should be limited to
      those without preoperative morbidity.

PMID- 9544827
TI  - Complications after surgery for gastric cancer in patients aged 80 years and
      over.
AB  - Recent studies have shown a considerable increase in the number of aged patients
      with gastric cancer. In this retrospective study, we report our 18-year
      experience with 110 patients aged 80 years and over affected with this neoplasm.
      Postoperative morbidity and mortality rates and risk factors affecting their
      incidence were examined by univariate and multivariate analysis. Operability and
      resectability rates were 70.9% and 47.3% respectively. Of the resective
      procedures, 41 (78.8%) were subtotal gastrectomies. In five cases (9.6%), we
      performed combined resections. Twenty-five patients (32.1%) experienced
      postoperative complications; overall mortality rate was 12.8% (10 patients). In
      resective procedures, morbidity and mortality were 26.9% and 3.8% respectively,
      which are very low rates compared to other Western reports. Statistical analysis
      identified the number of preexisting medical illnesses as an independent
      predictor of morbidity and mortality. Crude five-year survival rate of curatively
      resected cases was 43%. Although multiple medical illnesses involved much higher
      operative mortality, neither the presence of postoperative complications nor the
      number of preexisting medical illnesses significantly influenced five-year
      survival rate of curatively resected patients. With careful evaluation and
      selection of patients, correct treatment of concomitant diseases and adequate
      peri- and postoperative care, gastric surgery provides good immediate and long
      term results even in very old patients. Subtotal gastrectomy with limited
      lymphadenectomy should be the preferred procedure; total gastrectomy, combined
      resections and extended lymphadenectomy should be performed only when necessary,
      in patients with fewer than two illnesses. Surgery should be avoided in patients
      with highly advanced disease, if multiple medical illnesses are present.

PMID- 9544828
TI  - Macroscopic features at the deepest site of tumor penetration predicting liver
      metastases of colorectal cancer.
AB  - Liver metastasis is the gravest prognostic factor in colorectal cancer. To
      identify a reliable indicator for liver metastasis, we evaluated macroscopic
      features and seven established histopathological findings at the cut section
      containing the deepest penetration using univariate and multivariate analyses in
      417 colorectal cancers. Macroscopic features were divided into two types, streak
      type and non-streak type, according to the presence or absence of white streak(s)
      at the advancing margin of tumor invasion. Streak type was observed in 109
      patients (26%). The frequency of liver metastasis in streak type tumors (56%) was
      significantly higher than that in non-streak type tumors (13%) (p < 0.001). The
      white streak corresponded histologically with cancer cells showing focal
      dedifferentiation with marked stromal and perivascular fibrosis extending towards
      the serosa or adventitia. In 343 curatively treated patients, univariate analysis
      showed that recurrent liver metastasis was significantly associated with
      macroscopic features, venous invasion, focal dedifferentiation and lymph node
      metastasis. Multivariate analysis disclosed that macroscopic features and lymph
      node metastasis were independent indicators of liver metastasis. These
      macroscopic features, corresponding histologically to stromal behavior against
      invading cancer cells, are a simple and useful indicator of liver metastasis of
      colorectal cancer.

PMID- 9544829
TI  - Navoban (tropisetron, ICS 205-930) and dexamethasone combination in the
      prevention of vomiting for patients receiving preconditioning high-dose
      chemotherapy before marrow transplantation.
AB  - The anti-emetic efficacy of a combination of tropisetron and dexamethasone was
      studied in 33 patients who underwent bone marrow transplantation. Another 50
      patients receiving conventional anti-emetic therapies in bone marrow
      transplantation served as control. On the first and second days of
      preconditioning chemotherapy, 51% and 36% respectively of patients in the
      tropisetron and dexamethasone group did not experience vomiting, compared with
      only 12% and 10% of control group patients (P < 0.001). The mean number of
      episodes of vomiting in the tropisetron and dexamethasone group was also
      significantly lower than in the control group (0.97+/-1.65 vs 3.50+/-2.45 and
      1.30+/-1.40 vs 4.44+/-2.91 respectively, both P < 0.001). Control of vomiting in
      the two groups was not significantly different during days 3-6. Analysis of
      patients receiving busulfan and cyclophosphamide as the preconditioning regimen
      still showed better anti-emetic control in the tropisetron and dexamethasone
      group than in the control group on the first two days of treatment (total control
      rate 33.3% vs 6.5% and 44.4% vs 12.9% respectively, P < 0.001). Patients given
      tropisetron and dexamethasone combination more frequently suffered from dizziness
      and burning sensation of the chest. However, diarrhea and extrapyramidal symptoms
      were the most frequent adverse effects seen after using conventional anti-emetic
      combination. The combination of tropisetron and dexamethasone was thus superior
      to conventional anti-emetic combinations in preventing vomiting during
      preconditioning period of bone marrow transplantation. The adverse effects of
      this combination were minimal and well tolerated by patients.

PMID- 9544830
TI  - Results of a qualitative and field study using the WHOQOL instrument for cancer
      patients.
AB  - The main purpose of the study was to evaluate quality of life (QOL) among cancer
      patients using the WHOQOL-100 instrument and to see if any significant
      differences were seen in cancer stages, treatment status and prognosis. This
      study consisted of two parts; qualitative and quantitative. For the qualitative
      study, two focus groups were conducted by medical professionals to establish the
      applicability of the WHOQOL instrument in evaluating the QOL of cancer patients,
      but most participants were negative about using a generic instrument such as
      WHOQOL. For the quantitative study, 197 cancer patients (average age 55.86) from
      eight medical centers using the WHOQOL instrument, in addition to each patient's
      information sheet filled in by their own physicians, were analyzed. The average
      overall QOL score was 3.39. There was high reliability (Cronbach's alpha =
      0.9685) and a high correlation between the psychological and the environmental
      domains (r = 0.7021), the physical domain and the level of independence (r =
      0.6031) and social relations and the environment (r = 0.6856) and between health
      conditions perceived by patients and QOL scores. In addition, differences by
      gender, treatments and cancer sites were also found to be significantly different
      at the 5% significance level. The results indicated that the WHOQOL core
      instrument was sensitive enough to evaluate the QOL of cancer patients.

PMID- 9544831
TI  - Primary seminoma in the middle mediastinum: case report in a 69-year-old male.
AB  - Primary mediastinal seminoma is an uncommon tumor usually located in the anterior
      mediastinum. The majority of cases occur in young males. We report here an
      extremely rare case of a 69-year-old male with primary seminoma in the middle
      mediastinum. The patient had no complaints, but an abnormal shadow was seen in a
      routine chest X-ray. We performed a tumorectomy in the middle mediastinum, a
      thymectomy and an orchidectomy and added postoperative chemotherapy. It seems
      that the tumor was not associated with the thymus, so we believe the tumor did
      not stem from the embryonic thymus. Our case demonstrated that mediastinal
      seminoma does not always occur in the anterior mediastinum of young males.
      Although this case is rare, seminoma should be included among the possible
      diagnoses of a middle mediastinal mass.

PMID- 9544834
TI  - Research programs in Japan.

PMID- 9544833
TI  - Anastomotic recurrence after curative resection of a transverse colon carcinoma:
      a case report.
AB  - We report a case of anastomotic recurrence after curative surgery for transverse
      colon cancer in a 53-year-old man. The recurrence was first detected as a
      submucosal tumor 1.3 cm in diameter, located on the suture line, during an annual
      follow-up barium enema and colonoscopy. A repeat examination 3 months later
      showed the lesion to be a typical colon cancer, 2.5 cm in size, with a large
      ulcerated area. Right hemicolectomy was performed with curative intent.
      Anastomotic recurrence is much rarer after colonic resection than after anterior
      resection. This was the first time that we had detected a recurrent lesion as a
      submucosal tumor during annual follow-up examination.

PMID- 9544832
TI  - A case of malignant peritoneal mesothelioma showed complete remission with
      chemotherapy.
AB  - A 71-year-old woman presented with an abdominal mass and ascites and was
      subsequently admitted to our hospital in June 1995. Further examination revealed
      that the mass was malignant and, as a result, surgery was indicated. However, the
      mass demonstrated widespread peritoneal dissemination, which therefore could not
      be resected, and pathological findings suggested a malignant peritoneal
      mesothelioma. The patient showed a remarkable response to combined chemotherapy
      with an accompanying intraperitoneal injection of cisplatin and etoposide and an
      intravenous injection of caffeine. However, owing to side effects, this regimen
      was discontinued. The patient was administered a combination drug of uracil and
      tegafur (UFT) in addition to intraperitoneal injection of cisplatin as an
      outpatient. By the 223rd day after surgery, the tumor mass and ascites had
      completely disappeared according to the CT. Hence chemotherapy was judged to have
      resulted in complete remission. Such a marked response to chemotherapy is rare in
      an advanced malignant peritoneal mesothelioma such as the present case. Eight
      months later, the tumor recurred in the pleura. Another regimen of chemotherapy
      with cisplatin and CPT-11 was performed. However, this treatment proved
      ineffective. The patient subsequently died of respiratory failure in January 1997
      due to the mesothelioma. This is a case report of complete remission of malignant
      peritoneal mesothelioma by combined chemotherapy.

PMID- 9544835
TI  - A 50-year perspective of a family with chromosome-14-linked Alzheimer's disease.
AB  - A Swedish family with two generations suffering from presenile dementia with an
      unusually severe Alzheimer encephalopathy was first reported in 1946. The
      hypothesis that the disease was inherited through a dominant gene is strongly
      supported by the follow-up 50 years later of three additional generations and
      molecular genetic findings of a novel presenilin-1 gene mutation in the family.
      The pedigree contains six cases with well-documented dementia in four consecutive
      generations. The Alzheimer encephalopathy was unusually severe in the three cases
      studied post-mortem, with a pronounced involvement of the central grey
      structures, such as the claustrum, the nuclei around the third ventricle, the
      central thalamic nuclei and the brain stem. There were no vascular lesions and
      little amyloid angiopathy. All six affected cases showed the typical
      temporoparietal symptom pattern and other core symptoms of Alzheimer's disease,
      such as logoclonia, myoclonic twitchings and major motor seizures. Other
      predominant features were psychomotor slowness, increased muscular tension, a
      stiff stooped gait and a rapid loss of weight. The symptom pattern is
      convincingly explained by the consistent and severe involvement of cortical and
      central grey structures and is probably linked to the presenilin-1 gene mutation.

PMID- 9544836
TI  - Identification of CpG islands hypermethylated in human lung cancer by the
      arbitrarily primed-PCR method.
AB  - DNA hypermethylation is believed to be involved in human carcinogenesis, since it
      suppresses the transcription of defined genes and is associated with chromosomal
      instability. In this study, we identified CpG islands that are hypermethylated in
      human lung cancer by a modified arbitrarily primed-polymerase chain reaction
      method using genomic DNAs digested with a methylation-sensitive restriction
      enzyme, HpaII, as templates. When we analyzed genomic DNAs from normal lung
      tissues and non-small cell lung carcinoma cell lines using three arbitrary
      primers, three DNA fragments were amplified from lung cancer DNAs but not from
      normal lung DNAs. Restriction mapping and Southern blot analysis revealed that
      all of these bands were amplified from CpG islands that were hypermethylated in
      the lung cancer cell lines. These islands were mapped to chromosomes 4q34, 10q26
      and 17p13.1-p13.2, respectively, and these chromosomal regions were also
      hypermethylated in a subset of primary lung tumors in vivo. Thus, diverse
      chromosomal regions are hypermethylated in lung cancer cells. The results also
      indicate that this method is simple and effective for screening of CpG islands
      that are hypermethylated in cancer cells.

PMID- 9544837
TI  - Multiple different missense mutations in the pore region of HERG in patients with
      long QT syndrome.
AB  - Long QT syndrome (LQTS), is an inherited cardiac disorder in which ventricular
      tachyarrhythmias predispose affected individuals to syncope, seizures, and sudden
      death. Characteristic electrocardiographic findings include a prolonged QT
      interval, T wave alternans, and notched T waves. We have screened LQTS patients
      from 89 families for mutations in the pore region of HERG , the K+ channel gene
      previously associated with chromosome 7-linked LQT2. In six unrelated LQTS
      kindreds, single-strand conformation polymorphism analyses identified aberrant
      conformers in all affected family members. These conformers were not seen in over
      100 unaffected, unrelated control individuals, suggesting that they represent
      pathogenic LQTS mutations. DNA sequence analyses of the aberrant conformers
      demonstrated that they reflect five different missense mutations: V612L, A614V,
      N629D, N629S, and N633S. The missense mutation A614V was found in two unrelated
      families. Further functional studies will be required to determine what effect
      each of these changes may have on HERG channel function.

PMID- 9544838
TI  - Linkage of the apo CIII microsatellite with isolated low high-density lipoprotein
      cholesterol.
AB  - To evaluate whether a highly polymorphic microsatellite region within intron 3 of
      the apolipoprotein (apo) CIII gene is linked to the isolated low HDL-C phenotype,
      we studied eight unrelated probands (mean HDL-C = 10+/-5 mg/dl) and 157
      biological family members. After PCR amplification of genomic DNA and denaturing
      polyacrylamide gel electrophoresis, 26 alleles were identified in this
      microsatellite including 9 alleles heretofore unreported. Quantitative sib-pair
      linkage analysis demonstrated strong evidence of linkage between the isolated low
      HDL-C phenotype and the apo CIII microsatellite region (P = 0.007). The
      microsatellite was also linked to apo AI (P = 0.001), the primary apolipoprotein
      of HDL-C. Therefore, this highly polymorphic microsatellite region is a
      potentially important marker in the genetic evaluation of the isolated low HDL-C
      phenotype.

PMID- 9544839
TI  - Isolation of the human BACH1 transcription regulator gene, which maps to
      chromosome 21q22.1.
AB  - In order to contribute to the development of the transcriptional map of
      chromosome 21, we performed exon trapping using cosmid clones mapped in the
      region 21q22.1-22.2 and identified a number of potential exons. One of the
      trapped exons (Genbank No. AF026200) showed a strong homology with the mouse
      Bach1 gene (Genbank No. D86603), a transcription factor regulating gene
      expression. We then isolated the full-length coding region of the human BACH1
      gene using expressed sequence tags, reverse transcription-polymerase chain
      reaction and rapid amplification of cDNA ends. The predicted BACH1 protein
      contains 736 amino acids and is 88% identical to its mouse homolog. It contains
      basic leucine zipper and BTB-zinc finger domains (which are directly involved in
      DNA binding for transcription regulation). The BACH1 gene maps in a relatively
      gene-poor region on 21q22.1 in yeast artificial chromosome 814c1 of the
      collection of Chumakov et al. Northern blot analysis revealed that it is
      expressed as an mRNA species of approximately 5.8 kb in all 16 adult and 4 fetal
      tissues examined; an additional mRNA species of 2.8 kb was observed in adult
      testis. The contribution of the BACH1 gene to the pathophysiology of trisomy or
      monosomy 21 is unknown. In addition, no monogenic disorders associated with
      mutations in the BACH1 gene have yet been identified.

PMID- 9544840
TI  - Identification and characterization of a new human cDNA from chromosome 21q22.3
      encoding a basic nuclear protein.
AB  - Congenital heart disease (CHD) affects over 40% of Down syndrome (DS) patients.
      The region proposed to contain the gene(s) for DS CHD has been restricted to
      21q22.2-22.3, from D21S55 to MX1. The identification and functional
      characterization of the genes mapping to this region is a necessary step to
      understand the pathogenesis of CHD in DS. In an effort to contribute to the
      construction of a transcriptional map of the DS CHD region we have performed
      direct cDNA selection using a YAC contig that maps between ETS2 and D21S15 and
      cDNAs synthesised from fetal heart structures. Here we describe the
      identification and characterization of a new gene, WRB, that maps to 21q22.3
      between ACTL5 and HMG 14 and appears to be widely expressed in adult and fetal
      tissues. The new gene encodes a basic protein of unknown function containing a
      tryptophan-rich carboxyl-terminal region and a potential nuclear localization
      signal. Immunofluorescence analysis shows a predominant localization in the cell
      nucleus. The understanding of the biological function of the protein product
      should clarify the potential role of WRB in the pathogenesis of DS CHD.

PMID- 9544841
TI  - Novel mutations of the peripheral myelin protein 22 gene in two pedigrees with
      Dejerine-Sottas disease.
AB  - Peripheral myelin protein 22 (PMP22), a membrane glycoprotein, plays a
      significant role in the formation and/or maintenance of compact myelin in the
      peripheral nervous system. We studied two pedigrees with Dejerine-Sottas disease
      and identified two novel mutations in the PMP22 gene: one a 2-bp deletional
      mutation at nucleotide positions 426 and 427 of exon 4 (this is predicted to
      alter the reading frame at leucine 80 and thus to lead to frame-shifted
      translation), and the other a guanine to thymine substitution at nucleotide
      position 636 leading to a cysteine substitution for glycine 150. Both mutations
      were located in the putative transmembrane domains reported in many cases of
      Charcot-Marie-Tooth neuropathy, Dejerine-Sottas disease, and hereditary
      neuropathy with liability to pressure palsies. The results suggest an important
      role for the putative transmembrane domains of PMP22 in its function.

PMID- 9544842
TI  - A high risk phenotype of hypertrophic cardiomyopathy associated with a compound
      genotype of two mutated beta-myosin heavy chain genes.
AB  - Hypertrophic cardiomyopathy (HCM) is a genetically and clinically heterogeneous
      myocardial disease that is in most cases familial and transmitted in a dominant
      fashion. The most frequently affected gene codes for the cardiac (ventricular)
      beta-myosin heavy chain. We have investigated the genetic cause of an isolated
      case of HCM, which was marked by an extremely severe phenotype and a very early
      age of onset. HCM is normally not a disease of small children. The proband was a
      boy who had suffered cardiac arrest at the age of 6.5 years (resuscitation by
      cardioconversion). Upon screening of the beta-myosin heavy chain gene as a
      candidate, two missense mutations, one in exon 19 (Arg719Trp) and a second in
      exon 12 (Met349Thr), were identified. The Arg719Trp mutation was de novo, as it
      was not found in the parents. In contrast, the Met349Thr mutation was inherited
      through the maternal grandmother. Six family members were carriers of this
      mutation but only the proband was clinically affected. Segregation and molecular
      analysis allowed us to assign the Met349Thr mutation to the maternal and the
      Arg719Trp de novo mutation to the paternal beta-myosin allele. Thus, the patient
      has no normal myosin. We interpret these findings in terms of compound
      heterozygosity of a dominant (Arg719Trp) and a recessive (Met349Thr) mutation.
      Whereas a single mutated Arg719Trp allele would be sufficient to cause HCM, the
      concurrent Met349Thr mutation alone does not apparently induce the disease.
      Nevertheless, it conceivably contributes to the particularly severe phenotype.

PMID- 9544844
TI  - Genetic and immunohistochemical detection of mutations inactivating the
      keratinocyte transglutaminase in patients with lamellar ichthyosis.
AB  - Autosomal recessive lamellar ichthyosis is a clinically heterogeneous group of
      severe congenital keratinization disorders that is characterized by generalized
      hyperkeratosis and variable erythema. About half of the patients have mutations
      in the TGM1 gene, which encodes the keratinocyte transglutaminase. Linkage
      studies have shown that at least two further loci for autosomal recessive
      lamellar ichthyosis must exist. We present here two patients with lamellar
      ichthyosis caused by mutations in the TGM1 gene. The first patient is compound
      heterozygous for the novel missense mutation C53S and the splice mutation A3447G.
      The second patient, a child of consanguineous parents from Tunisia, is homozygous
      for the unknown nonsense mutation W263X. This is the first report of a mutation,
      C53S, that affects the region of the keratinocyte transglutaminase that is
      essential for anchorage of the enzyme to the plasma membrane. A novel, rapid in
      situ transglutaminase activity assay revealed the absence of keratinocyte
      transglutaminase activity in both patients. The mutations described are hence
      causative for the ichthyosis phenotype.

PMID- 9544843
TI  - Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type
      II.
AB  - Tyrosinemia type II (Richner-Hanhart syndrome, RHS) is a disorder of autosomal
      recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis,
      mental retardation, and elevated blood tyrosine levels. The disease results from
      deficiency in hepatic tyrosine aminotransferase (TAT). We have previously
      described one deletion and six different point mutations in four RHS patients. We
      have now analyzed the TAT genes in a further seven unrelated RHS families from
      Italy, France, the United Kingdom, and the United States. We have established PCR
      conditions for the amplification of all twelve TAT exons and have screened the
      products for mutations by direct sequence analysis or by first performing single
      strand conformation polymorphism analysis. We have thus identified the presumably
      pathological mutations in eight RHS alleles, including two nonsense mutations
      (R57X, E411X) and four amino acid substitutions (R119W, L201R, R433Q, R433W).
      Only the R57X mutation, which was found in one Scottish and two Italian families,
      has been previously reported in another Italian family. Haplotype analysis
      indicates that this mutation, which involves a CpG dinucleotide hot spot, has a
      common origin in the three Italian families but arose independently in the
      Scottish family. Two polymorphisms have also been detected, viz., a protein
      polymorphism, P15S, and a silent substitution S103S (TCG-->TCA). Expression of
      R433Q and R433W demonstrate reduced activity of the mutant proteins. In all,
      twelve different TAT gene mutations have now been identified in tyrosinemia type
      II.

PMID- 9544845
TI  - X chromosome-inactivation patterns in patients with Rett syndrome.
AB  - Rett syndrome (RS) is a complex and severely disabling neurologic disorder,
      restricted to females. As non-random X inactivation could indicate that the X
      chromosome has a role in the etiology of the syndrome, we performed molecular
      analysis based on the differential methylation of the active and inactive X
      chromosomes with probe M27beta, taking into account the parental origin of the
      two Xs, in 24 RS girls (including a pair of concordant monozygote twins), 22
      mothers, and a control group of 30 normal women. The results showed a
      significantly (Fisher's exact test) increased frequency of skewed X inactivation
      in lymphocytes from 15/23 RS compared with 4/22 mothers (P = 0.0031) and 6/30
      controls (P = 0.0021). Our results, together with those from the literature,
      showed that as a group, RS patients are apparently more prone to skewed X
      inactivation than their mothers and normal controls, and this suggests that the X
      chromosome is somehow involved in RS etiology.

PMID- 9544846
TI  - Exclusion of five subunits of cGMP phosphodiesterase in Leber's congenital
      amaurosis.
AB  - Leber's congenital amaurosis (LCA) is the earliest and most severe of all
      inherited retinal dystrophies. Recently, we mapped an LCA gene to chromosome
      17p13.1 (LCA1) and ascribed the disease to mutations of the retinal guanylate
      cyclase (ret GC) gene in a subset of families of North African ancestry. Owing to
      the genetic heterogeneity of LCA and considering that LCA1 results from an
      impaired production of cGMP in the retina (with permanent closure of cGMP-gated
      cation channels), we hypothesized that the activation of the cGMP
      phosphodiesterase (PDE) could trigger the disease by lowering the intracellular
      cGMP level in the retina. The rod and cone cGMP-PDE inhibitory subunits were
      regarded therefore as candidate genes in LCA. Here, we report the exclusion of
      five rod and cone cGMP-PDE subunits in LCA families unlinked to chromosome 17p13.

PMID- 9544848
TI  - Allele frequencies of hereditary hemochromatosis gene mutations in a local
      population of west Brittany.
AB  - Hereditary hemochromatosis (HH) gene mutations, C282Y and H63D, have been
      screened in a cohort of 254 presumably healthy persons originating from a western
      region of France. The carrier frequencies of these mutations and the incidence of
      HH have been estimated and compared with those of other studies. This cohort
      contains two C282Y/C282Y genotypes and has the highest C282Y heterozygosity
      frequency (17.46%) ever reported.

PMID- 9544847
TI  - Familial mitochondrial DNA depletion in liver: haplotype analysis of candidate
      genes.
AB  - Two sons and one daughter of healthy consanguineous parents presented with fatal
      hepatic failure in association with severe depletion of mitochondrial (mt)DNA in
      liver; a third son is healthy. Other published cases of mtDNA depletion concern
      single members of a family, which excludes the use of haplotype analysis. In the
      family presented here, the inheritance of the genes for mitochondrial
      transcription factor A (mtTFA), nuclear respiratory factor 1 (NRF-1),
      mitochondrial single-stranded DNA-binding protein (mtSSBP), and endonuclease G
      (EndoG) was studied using microsatellite markers linked to these genes. The
      inheritance of the gene for mtDNA polymerase (pol gamma) was studied using a
      polymorphic CAG repeat present within the coding region of the gene. EndoG and
      mtSSBP were excluded, but mtTFA remains a candidate. Pol gamma or NRF-1
      involvement would be compatible only with autosomal dominant inheritance. Coding
      sequence analysis of NRF-1 and mtTFA revealed no novel mutations in affected
      individuals.

PMID- 9544849
TI  - Mutation analysis of the dystrophin gene in Southern French DMD or BMD families:
      from Southern blot to protein truncation test.
AB  - Data from 6 years of experience in molecular diagnosis of Duchenne (DMD) and
      Becker (BMD) muscular dystrophy in Southern France are reported. DMD and BMD
      patients have been extensively analyzed for deletions and for point mutations in
      the dystrophin gene. By scanning the whole coding sequence as reverse-transcribed
      from lymphocytes or muscular RNA by the protein truncation test, we have reached
      a minimum of an 86% detection rate for point mutations responsible for DMD; these
      mutations consist of nonsense, frameshifting, and splicing mutations. Four of 12
      small alterations identified in our sample are novel and described in this study.
      We also present an improved protocol for the automated detection of fluorescently
      labeled duplex polymerase chain reactions of six known intragenic microsatellites
      (Dys II, TG 15, STRs 44, 45, 49, and 50). Accurate sizing of the alleles at each
      locus was performed, and we elucidated the sequence of several repeat units.
      Allele frequencies at each of the six microsatellite loci and at one restriction
      fragment length polymorphism site (intron 16/TaqI) were defined in a sample of
      normal, DMD, and BMD X chromosomes from Southern France. The determination of the
      grandparental origin of either deletions or point mutations revealed differences
      depending on the type of the mutation, with most of the deletions occurring in
      oogenesis and most of the point mutations occurring in spermatogenesis.

PMID- 9544850
TI  - Analysis of low density lipoprotein receptor gene mutations and microsatellite
      haplotypes in Greek FH heterozygous children: six independent ancestors account
      for 60% of probands.
AB  - This study reports the characterization of 60% of low density lipoprotein
      receptor (LDLR) gene mutations in 150 unrelated Greek familial
      hypercholesterolaemia (FH) heterozygous children by the analysis of six LDLR gene
      mutations. The linkage disequilibrium of two polymorphic microsatellites (D19S394
      and D19S221) flanking the LDLR gene on chromosome 19 to the four most common
      mutations strongly suggests that each mutation is identical-by-descent in the
      probands included in this study (this is also supported by the geographical
      distribution of FH families with these mutations throughout Greece) and permits
      an estimation of the number of generations from a common ancestor for each
      mutation. The characterization of 60% of LDLR mutations in a representative
      sample of Greek FH heterozygotes provides a basis for the diagnosis of FH through
      DNA analysis in Greece, by using single-strand conformation polymorphism analysis
      followed by allele-specific oligonucleotide hybridization (exon 6 mutations) or
      restriction endonuclease analysis (C152R, V408M). A rapid diagnostic assay
      positive for the mutation has been developed for the most common mutation, G528D.
      The application of simple DNA diagnostic assays for LDLR mutation analysis are
      appropriate for the early identification of FH heterozygotes in Greece and are
      useful for the primary prevention of coronary artery disease.

PMID- 9544851
TI  - Breast cancer risk assessment: use of complete pedigree information and the
      effect of misspecified ages at diagnosis of affected relatives.
AB  - Reliable risk estimates for hereditary breast cancer are important for the
      genetic counseling of women who have one or more first- and/or second-degree
      relatives affected by the disease. If no mutation analysis of known high
      penetrance breast cancer genes is performed, risk estimation is often based on
      published reference tables. These tables express a woman's age-specific risk of
      breast cancer as a function of the ages at diagnosis of one or two affected
      relatives with different degrees of relationship to the counselee. However,
      unaffected relatives are not taken into account when these estimates are derived.
      We report here the extent to which risk estimation is influenced by the number
      and ages of any unaffected relatives and by the exact genealogical relationship
      between the proband and affected relative rather than merely the degree.
      Additionally, we describe the sensitivity of risk estimates when ages at
      diagnosis of affected relatives are misspecified because of inaccurate
      information supplied by the counselee. We determined a proband's probability of
      being a carrier of a highly penetrant breast cancer susceptibility gene, such as
      BRCA1 or BRCA2, by likelihood calculations that take into account information
      from the entire pedigree. This genetic risk was used to estimate a phenotypic
      lifetime breast cancer risk, which was compared with the risks derived from the
      published reference tables. We demonstrate numerically that the tabulated values
      tend to over-estimate the probands risk and that the extent of over-estimation
      depends greatly on the number and ages of unaffected relatives. The validity of
      the relatives ages at diagnosis can affect risk predictions considerably in small
      families with two or three affected relatives. Furthermore, the magnitude of the
      estimated breast cancer risks depends upon the assumed genetic model and can
      therefore vary appreciably when different penetrance estimates are used.

PMID- 9544852
TI  - Variable number tandem repeat polymorphism of the mucin genes located in the
      complex on 11p15.5.
AB  - A family of four genes that encode major secreted mucins (MUC6, MUC2, MUC5AC and
      MUC5B) map to within 400 kb on chromosome 11p15.5. These genes contain long
      stretches of tandem repeats of sequence that encode serine- and threonine-rich
      domains but that otherwise show no similarity from gene to gene, and regions of
      unique sequence domains that do show evidence of sequence homology. We have
      previously reported the existence of polymorphism in three of these genes but the
      extent and nature of this allelic variation is now described here in detail.
      Variable number tandem repeat polymorphisms of MUC6, MUC2 and MUC5AC are
      predicted to encode mucin polypeptides that differ in length. In the case of MUC2
      and MUC6 these length differences are substantial (up to twofold). MUC5B in
      contrast does not show common allele length variation. Three MUC2 mutations are
      reported, none of which are associated with the meiotic recombinations previously
      observed in this region of chromosome 11.

PMID- 9544853
TI  - Two novel mutations in exons 19a and 20 and a BsaBI [correction of BsaI]
      polymorphism in a newly characterized intron of the neurofibromatosis type 1
      gene.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder. It is
      caused by mutations in the NF1 gene, which comprises 60 exons and is located on
      chromosome 17q11.2. A total of 170 unrelated NF1 patients were screened for
      mutations in four exons by temperature-gradient gel electrophoresis. Preparatory
      work revealed the presence of a previously uncharacterized intron (19a) in what
      was previously designated exon 19; this allowed us to develop assays for genomic
      mutation screening in the newly defined exons 19a and 19b. Two novel NF1
      mutations were detected: a single-base insertion in exon 19a creating a
      frameshift, and a second mutation affecting the splice donor site of intron 20
      and leading to skipping of exon 20. A novel BsaBI polymorphism was identified in
      intron 19a.

PMID- 9544854
TI  - Relationship of the angiotensin-converting enzyme gene polymorphism to glucose
      intolerance, insulin resistance, and hypertension in NIDDM.
AB  - The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism has been shown to be associated with
      cardiovascular and renal diseases in diabetes mellitus, but the mechanism
      underlying this association is not known. In addition, recent studies of the
      effect of the ACE gene on blood pressure have yielded conflicting results.
      Therefore, we studied the association of the ACE gene I/D polymorphism with
      glucose intolerance and insulin resistance, and the contribution of this locus to
      genetic susceptibility to hypertension in non-insulin-dependent diabetic mellitus
      (NIDDM). We analysed the ACE genotype in 84 unrelated NIDDM patients with a known
      disease duration of less than 1 year and in 115 age- and sex-matched controls.
      The I/D polymorphism was determined by the polymerase chain reaction. There were
      no differences in ACE genotype distribution and allele frequencies between
      patients with NIDDM and nondiabetic controls. The frequencies of the D and I
      alleles in both groups were identical, viz., 0.65 and 0.35, respectively. The
      NIDDM patients with the DD genotype had significantly higher blood glucose levels
      in the oral glucose tolerance test than those with the other genotypes; the
      incremental glucose area under the curve in the order of II, ID, and DD was 7.2+/
      2.4, 9.2+/-4.0, and 10.7+/-2.7 mmol/l x h (II vs ID vs DD, P=0.0066 by ANOVA). No
      significant difference was found between the ACE genotype and serum insulin
      values. Similarly, there were no differences in body mass index, blood pressure,
      or serum lipids between the three genotypes. Among the non-diabetic controls,
      there was no statistically significant association of the I/D polymorphism with
      serum lipids, blood glucose levels, serum insulin concentrations, or blood
      pressure values. In conclusion, NIDDM patients with the DD genotype have higher
      blood glucose levels and are more glucose intolerant; this may help to explain
      the reported association between the D allele and vascular complications in
      NIDDM.

PMID- 9544855
TI  - A meta-analysis of clinical studies on the caries-inhibiting effect of fluoride
      gel treatment.
AB  - A meta-analysis was performed on published data on the caries-inhibiting effect
      of fluoride gel treatment in 6- to 15-year-old children. The purposes of this
      meta-analysis were: (1) to calculate the overall caries-inhibiting effect of
      clinical fluoride gel treatment studies, based on explicit selection criteria,
      and (2) to explore factors potentially modifying the effect of fluoride gel
      treatment in caries prevention, concerning the baseline caries prevalence of the
      target population, the general fluoride regimen, and application features. The
      caries-inhibiting effect of fluoride gel application was assessed by the
      prevented fraction and the 'number needed to treat'. The overall prevented
      fraction of the fluoride gel treatment studies, indicating the reduction of
      caries incidence by fluoride gel treatment relative to the incidence in the
      control group, was 22% (95% CI = 18-25%). Multiple regression analysis showed no
      significant influence on the prevented fractions for the variables 'baseline
      caries prevalence', 'general fluoride regimen', 'application method', and
      'application frequency'. The 'number needed to treat' (NNT), indicating the
      number of patients that need to be treated in order to prevent 1 DMFS, estimated
      the efficiency of fluoride gel treatment according to the caries incidence of the
      target population, including cost/effect relations. It was found that the NNT =
      18 in a population with caries incidence 0.25 DMFS per year, and NNT = 3 in a
      population with caries incidence = 1.5 DMFS per year (treatment duration 1 year).
      From the standpoint of cost-effectiveness, the additional effect of fluoride gel
      treatment in current low and even moderate caries incidence child populations
      must be questioned.

PMID- 9544857
TI  - The isolation of Actinomyces naeslundii from sound root surfaces and root carious
      lesions.
AB  - The isolation of Actinomyces naeslundii from sound, exposed root surfaces (n =
      56) and soft and leathery root carious lesions (n = 71) was investigated. Root
      carious lesions were sampled after the removal of overlying plaque. Supragingival
      plaque or carious dentine was sampled using a sterile excavator, the samples were
      disaggregated and cultured on both selective and non-selective media. A.
      naeslundii isolates were identified to the genospecies using specific antisera.
      Significantly greater numbers and proportions of A. naeslundii genospecies 2 than
      A. naeslundii genospecies 1 were isolated from all sites sampled. There was no
      significant difference between the numbers and proportions of the two genospecies
      isolated from leathery and soft lesions. The relationship between the presence of
      A. naeslundii genospecies and aciduric and acidogenic organisms was investigated.
      Those sound exposed root surfaces from which A. naeslundii genospecies 1 and/or 2
      were isolated yielded significantly lower numbers of lactobacilli and yeasts than
      the surfaces from which A. naeslundii were not isolated. This difference was also
      found in leathery lesions but not soft root carious lesions. The microflora of
      soft root carious lesions was found to comprise primarily gram-positive
      pleomorphic rods which formed 70+/-7.8% of the flora, while in plaque from
      exposed root surfaces and in infected dentine from leathery lesions the gram
      positive pleomorphic rods represented only 35% of the flora.

PMID- 9544856
TI  - Root caries and some related factors in 88-year-old carriers and non-carriers of
      Streptococcus sobrinus in saliva.
AB  - The prevalence of caries on exposed root surfaces in 88-year-old subjects with
      and without salivary levels of Streptococcus sobrinus was studied. Ninety-two
      individuals were examined with regard to root caries lesions and fillings. The
      root caries index (RCI) was calculated and related to salivary flow rate and
      buffer capacity, plaque score and salivary counts of Streptococcus mutans, S.
      sobrinus and lactobacilli. In 89 subjects with exposed root surfaces, all but 2
      harbored mutans streptococci; 51 subjects carried S. mutans only, 35 both S.
      sobrinus and S. mutans, and 1 S. sobrinus only. The RCI was significantly higher
      in persons with than those without S. sobrinus (p < 0.05). Subjects with both S.
      sobrinus and S. mutans had higher counts of total mutans streptococci and
      lactobacilli than subjects with only S. mutans (p < 0.05). The RCI was
      significantly correlated to S. sobrinus and S. mutans (p < 0.05). The positive
      correlation between the RCI and S. sobrinus was still significant when the other
      tested variables were kept constant, whereas the correlation between the RCI and
      S. mutans was weaker when S. sobrinus and lactobacilli were kept constant. The D
      component of the RCI (DSr%) was significantly correlated to S. sobrinus, S.
      mutans and lactobacilli, whereas the F-component of the RCI showed no significant
      correlation to any of the tested variables. A stepwise multiple correlation
      showed that the variance of DSr% was best explained in the S. sobrinus carriers
      by S. sobrinus and the salivary buffer effect, and in the non-carriers by S.
      mutans.

PMID- 9544858
TI  - A descriptive report of the effects of a 16-month xylitol chewing-gum programme
      subsequent to a 40-month sucrose gum programme.
AB  - A previous caries trial (Belize studies) involved the usage of sucrose chewing
      gum for a period of 40 months in one group of initially 10-year-old subjects in
      an environment of high sugar consumption, high caries activity, and limited
      access to restorative care. After the termination of the 40-month supervised
      sucrose gum usage, the 109 subjects of the original sucrose group retrieved at
      the endpoint of the original trial were invited to participate in a xylitol
      chewing-gum programme (involving the usage of the '100% pellet-shaped formular')
      for 16 months. The average daily consumption level of xylitol was up to 14 g per
      subject, normally used in seven daily chewing episodes. Although most subjects
      used chewing-gum at schools and received their gum portions from a school
      official, gum chewing during these 16 months was mostly unsupervised. After 16
      months, 83 subjects (76%; mean age 14.9 years) were retrieved. The caries status
      of these subjects was examined by the same calibrated, blinded examiners as in
      the original trial. To mask the examiners, 141 similar non-participating subjects
      were recruited from the same school classes and were examined in a random order
      with the gum-using subjects, according to the same standard routine. The
      intensified xylitol gum usage for 16 months was associated with a reduction of
      the mean DMFS score from 10.9 (at 40 months) to 9.3 (at 56 months, p = 0.0013)
      and a reduction in caries rate from 20.1 caries onsets per 1,000 surface-years
      (40-month period average rate) to 10.2 caries onsets per 1,000 surface-years. The
      reduction in DMFS score resulted mostly from the change in the D component of the
      index and possibly reflected a stabilisation of the caries process and
      rehardening of some caries lesions to a non-progressive carious state.

PMID- 9544859
TI  - Comparison of the efficacy of three different chlorhexidine preparations in
      decreasing the levels of mutans streptococci in saliva and interdental plaque.
AB  - The aim of the present study was to evaluate and compare the effects of three
      different chlorhexidine (CHX)-containing preparations on mutans streptococci (MS)
      levels in interdental plaque and whole saliva. Ninety-three healthy school
      children (8-10 years old) with high scores of salivary MS were selected by a
      screening procedure and randomised into three equally sized groups. MS were
      enumerated at all mesial interdental sites of the first permanent molars with aid
      of a modified chairside technique. The patients were then treated three times
      within 2 weeks with either a 1% CHX/thymol-containing varnish (group A) or a 1%
      CHX gel (group B), or they were subjected to daily supervised toothbrushing with
      a 0.4% CHX dentifrice for 1 month (group C). Follow-up samples of saliva and
      plaque from the interdental sites were collected 1 and 3 months after termination
      of treatment. A statistically significant reduction of MS levels in saliva and
      interdental plaque was found in all groups after 1 month. The CHX-containing
      dentifrice (group C) was the most effective method in reducing MS levels in
      saliva, and a significantly stronger (p < 0.05) suppression was found after 1 and
      3 months when compared with the gel and the varnish forms. The gel (group B)
      tended to be slightly more effective than the varnish (group A). In the
      interdental plaque, the reduction of MS was less marked than in the saliva, and
      the three groups exhibited MS reductions of similar magnitude (20%) and duration,
      persisting up to 3 months. However, a high proportion (approximately 50%) of all
      interdental sites were relatively unaffected by the treatments. In conclusion,
      our results suggest that the interdental MS colonisation was difficult to combat,
      irrespective of CHX preparation and method, while the salivary levels were more
      easily affected. Daily tooth-brushing with a CHX-containing dentifrice was more
      effective in reducing MS in saliva compared with the gel or varnish applications.

PMID- 9544860
TI  - Three-year survival of one-surface ART restorations and glass-ionomer sealants in
      a school oral health programme in Zimbabwe.
AB  - An oral health care programme in secondary schools using the atraumatic
      restorative treatment (ART) approach for dental caries was started in 1993. Glass
      ionomer (restorative type II, 1) was used as the restorative and sealant
      material. Sealants were placed using the 'press-finger' technique. Results after
      3 years revealed a survival percentage for one-surface ART restorations of 85.3
      (95% CL: 89.7-80.9%), which ranged from 96.1 to 69.3% per operator. Failures were
      related to 'unacceptable marginal defects' (8.1%), 'falling out' (6.1%) and
      'excessive wear' (2.5%). Of the 33 failed one-surface ART restorations, 17 were
      material-related, 7 had caries and no information was available for 9
      restorations. Sealants were placed only on surfaces diagnosed as early enamel
      lesions and on some small dentinal lesions. After 3 years, 50.1% (95% CL: 55.1
      45.1%) of the fully and partially retained sealants survived with a range of 68.5
      25.9% per operator. Regardless of the low rate of retention, the sealed surfaces
      had a 4 times lower chance of developing caries than unsealed surfaces with early
      enamel lesions over the 3-year period. The retention of sealants and the survival
      of one-surface ART restorations were influenced by an operator effect. The mean
      treatment time for one-surface ART restorations without chairside assistance was
      22.1 min (range per operator of 19.8-23.6 min), whilst the mean time for placing
      sealants was 9.3 min (range per operator of 8.2-10.8 min). It is concluded that
      the ART approach and the use of glass-ionomer sealants have made preventive and
      restorative dental care available for this student population and further that
      ART seems to be appropriate for population groups currently not receiving
      preventive and restorative dental care.

PMID- 9544861
TI  - The effect of a knowledge-based, image analysis and clinical decision support
      system on observer performance in the diagnosis of approximal caries from
      radiographic images.
AB  - The aim of this study was to investigate the effect of a knowledge-based image
      analysis and clinical decision support system (CariesFinder, CF) on diagnostic
      performance and therapeutic decisions. The study material consisted of
      radiographic images of 102 approximal surfaces, 35 sound, 67 caries (25 caries
      and cavitated and 42 caries). Sixteen general practitioners were presented with
      (1) radiographic film images and (2) digital filmless images with the results of
      CF. The viewers were asked to respond whether approximal caries was present and
      whether a restoration was indicated. Responses were analyzed for accuracy,
      sensitivity, specificity and agreement. Further, the practitioners were ranked
      according to the accuracy of their restorative decisions and assigned to ten
      overlapping groups of 7 practitioners. For each group the diagnostic and
      therapeutic decisions were then examined for unanimity. The parameters of
      accuracy, sensitivity and specificity were then established for each group based
      on only unanimous, correct decisions. The diagnostic and therapeutic accuracy of
      CF alone was equal or superior to the decisions of the practitioners viewing film
      images alone. For unanimous decisions, CF alone was more accurate than the most
      accurate group of practitioners and made fewer incorrect decisions to restore non
      cavitated surfaces than the practitioners. In general, dental practitioners
      viewing the results of CF significantly increased their ability to diagnose
      caries correctly, their overall diagnostic accuracy, and their ability to
      recommend restorations for cavitated surfaces. There was a decrease in the
      accuracy of their restorative decisions overall and in the specificity in
      particular.

PMID- 9544862
TI  - Human enamel as a substrate for in vitro acid dissolution studies: influence of
      tooth surface and morphology.
AB  - The variation in susceptibility of enamel to acid dissolution has been
      quantitatively assessed in vitro by examination of different surfaces of both
      maxillary and mandibular teeth of different morphology obtained from a pool of
      sound human teeth. The lingual/palatal surfaces of all teeth showed greater
      susceptibility to acid dissolution than the corresponding labial/buccal surfaces.
      The palatal surface of the maxillary teeth appeared more susceptible to acid than
      the lingual surface of the corresponding teeth in the mandible. The palatal
      surfaces of the maxillary teeth showed least variation in acid susceptibility,
      whilst the lingual surfaces of mandibular teeth and buccal/labial surfaces of
      teeth from both jaws showed much more variation between teeth of different
      morphology. These differences in susceptibility to acid dissolution probably
      reflect both developmental differences and post-eruptive changes in enamel and
      may contribute to the clinical presentation of dental disease. Importantly, the
      data indicates that careful selection of teeth for in vitro study of enamel
      dissolution processes is essential to minimise inter-sample variation. For such
      purposes, the palatal surface of the maxillary teeth appears to be most suitable.

PMID- 9544863
TI  - Inhibition of dentin demineralization by fluoride in vitro.
AB  - Compared with the knowledge accumulated on enamel-fluoride interactions,
      relatively little data is available regarding fluoride effects on dentin. This
      applies to both laboratory and clinical studies into the efficacy of fluoride
      schemes for the prevention of root surface caries. This study aimed to determine
      the effects of fluoride and pH on the demineralization of dentin, such as to
      provide information necessary to develop preventive programmes. Bovine dentin
      blocks were subjected to undersaturated calcium- and phosphate-containing
      solutions in the pH range 4.0-6.0 with fluoride added at concentrations between
      0.5 and 10 ppm. Non-fluoride solutions served as controls. Mineral loss was
      assessed chemically and by transversal microradiography. Comparisons were made
      with similar studies on enamel demineralization. The results showed that
      demineralization of dentin depends on both pH and fluoride concentration in the
      demineralizing solution. Inhibition of demineralization that could be relevant
      from a clinical point of view was found at fluoride values 5-10 times the
      corresponding values for enamel. Also rapid depletion of fluoride from the
      solutions was observed, indicating the high uptake capacity of dentin for
      fluoride. Lesion depth depended on pH of the solution while the fluoride levels
      were associated with the surface layer, both in mineral content and depth. For
      dentin we propose a demineralization mechanism where acid penetrates rapidly into
      the tissue, presumably through the tubules, after which the released calcium and
      phosphate is partly trapped by the inward diffusing fluoride. This leads to the
      formation of a surface layer, which may even be hypermineralized compared to
      sound dentin.

PMID- 9544864
TI  - The production of subsurface artificial caries lesions on third molar teeth.

PMID- 9544865
TI  - Effect of antihypertensive treatment on cardiac and subcutaneous artery
      structure: a comparison between calcium channel blocker and thiazide-based
      regimens.
AB  - The effects of two antihypertensive regimens (isradipine and hydrochlorothiazide
      amiloride) on the ratio between media thickness and lumen diameter of
      subcutaneous arteries and on left ventricular mass in essential hypertension were
      compared. Fifty patients, aged 46.3+/-8 (mean+/-SD) years, with newly diagnosed
      or poorly controlled essential hypertension were randomized to treatment with
      either isradipine or hydrochlorothiazide-amiloride. Atenolol and hydralazine were
      added in both groups as secondary and tertiary drugs, respectively, when needed
      for normalization of diastolic blood pressure. A subcutaneous gluteal biopsy was
      taken surgically before medication and again after 9 months of successful
      antihypertensive treatment. Two small resistance arteries were isolated from each
      biopsy and mounted in a Mulvany-Halpem isometric small vessel myograph. The media
      thickness-to-lumen diameter ratio (percentage) of the vessels was measured under
      standardized conditions and meaned. Left ventricular mass (LVM) index was
      determined by echocardiography according to the Penn convention. Ten patients
      were treated with isradipine as monotherapy, whereas only one patient was well
      controlled on diuretics as monotherapy. Mean blood pressure was reduced equally
      with the two regimens, from 131+/-9 mm Hg to 101+/-10 mm Hg with the isradipine
      and from 128+/-9 mm Hg to 99+/-7 mm Hg with the thiazide/atenolol regimen. LVM
      decreased significantly in both groups by 130+/-75 g with the isradipine-based
      regimen and by 70+/-53 g with the hydrochlorothiazide/atenolol-based regimen. The
      reduction of LVM was significantly greater on the isradipine-based regimen than
      on the thiazide-based regimen (P < .01). There was a significant reduction of
      media thickness-to-lumen diameter ratio during treatment with the isradipine
      based regimen from 10.9% to 8.8% (P < .01). The reduction in the thiazide regimen
      was from 9.7% to 8.5%, which was not significant (P = .07). The study
      demonstrated significant reduction of hypertensive changes in peripheral
      resistance artery structure during antihypertensive treatment with an isradipine
      based regimen. The thiazide/betablocker-based regimen did not have a significant
      effect on the vessels. Significant reduction of LVM was achieved with both
      isradipine-based and thiazide/atenolol-based regimens. The reduction of LVM
      obtained with the isradipine-based regimen was significantly greater than that of
      the thiazide/atenolol-based regimen.

PMID- 9544866
TI  - Little effect of ordinary antihypertensive therapy on nocturnal high blood
      pressure in patients with sleep disordered breathing.
AB  - The antihypertensive effects of four different antihypertensive medications (beta
      blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release]
      2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting
      enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered
      breathing and hypertension were compared by the ambulatory blood pressure
      measurement (ABPM). Eighteen patients were randomized in a double-blind,
      crossover fashion to receive each of the four different medications for 8 weeks.
      ABPM was performed at baseline and after an 8-week treatment with these
      medications. A 2- to 3-week washout period occurred both at baseline and between
      each of the four medications. Three patients were omitted from statistical
      analysis because of technical problems of ABPM. Atenolol, isradipine SRO, and
      spirapril decreased significantly (P < .01) the mean 24-h systolic blood
      pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased
      significantly after all four medications: 12 (SD+/-14) mm Hg with atenolol, 7
      (SD+/-10) mm Hg with isradipine SRO, 3 mm Hg (SD+/-14) with HCTZ, and 6 (SD+/-15)
      mm Hg with spirapril (P < .01). During nighttime none of the medications reduced
      the mean diastolic or systolic blood pressure significantly. According to the 24
      h blood pressure curve the influence of these four medications during the whole
      measurement period was not similar. Atenolol and spirapril lost their
      antihypertensive effect during the early morning hours. The antihypertensive
      effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no
      medication was >0.50. Negative correlation was observed between the apnea time
      and the mean systolic 24-h (r = -0.604, P = NS) and the mean systolic nocturnal
      blood pressure change (r = -0.590, P = NS). Our study revealed that the daytime
      high blood pressure was quite easily controlled by the ordinary monotherapy in
      these patients with partial upper airway obstruction and hypertension. Instead
      none of the medications used decreased nocturnal high blood pressure markedly.

PMID- 9544867
TI  - QT dispersion in dipper- and nondipper-type hypertension.
AB  - The aim of this study was to identify the relationship of QT dispersion on 12
      lead electrocardiograms and left ventricular mass index on echocardiograms
      associated with the circadian rhythm of blood pressure (BP). Heart rate and BP
      were monitored every 30 min for 48 h in 62 patients with essential hypertension
      using an ambulatory BP monitoring device. The patients were divided into four
      groups according to gender and circadian BP pattern (nocturnal BP dipper or
      nondipper). The patients were classified as dippers if their daytime BP decreased
      by at least 10% during the night and all the other subjects were classified as
      nondippers. Age, body mass index, and 48-h mean BP were similar among the four
      groups. During the night-rest period, the systolic and diastolic BP were
      significantly decreased in dipper-type hypertensives. The maximum QTc interval
      and QTc dispersion were longer in nondippers than in dippers. Left ventricular
      mass index (LVMI) had a tendency to increase in nondippers. The nocturnal
      reduction of BP significantly correlated with QTc dispersion and LVMI. The QTc
      dispersion significantly correlated with LVMI and interventricular septum
      thickness.

PMID- 9544868
TI  - Left ventricular geometric patterns and QT dispersion in borderline and mild
      hypertension: their evolution and regression.
AB  - To investigate whether QT dispersion increases in borderline and mild
      hypertension during a longitudinal observation of > 3 years and whether it is
      improved with medications, left ventricular geometric patterns and QT dispersion
      were studied with special regard to their longitudinal changes in 85 male
      borderline and mild hypertensive subjects with left ventricular mass index < 125
      g/m2. These subjects were followed for > 3 years without medication. Thirty-two
      patients with a left ventricular mass index > 125 g/m2 at the end of follow-up
      period were further observed using antihypertensive drugs for an additional 3
      years. Echocardiograms and electrocardiograms were obtained at the beginning and
      end of the follow-up period. At the end of the follow-up period, subjects were
      classified into four groups based on ventricular geometric patterns determined by
      left ventricular mass index and relative wall thickness in diastole. The QT
      dispersion was greater in patients with concentric hypertrophy (56+/-18 msec)
      than in patients with normal geometry (41+/-17 msec) (P < .05) and increased
      significantly in the former group during the follow-up period. After medication,
      the left ventricular mass index regressed and the QT dispersion decreased (from
      55+/-21 to 50+/-26 msec, P < .01) in these patients. Thus, these findings suggest
      that changes in the QT dispersion reflect both concentric evolution and
      regression of left ventricular hypertrophy.

PMID- 9544869
TI  - Aortic stiffening does not predict coronary and extracoronary atherosclerosis in
      asymptomatic men at risk for cardiovascular disease.
AB  - Stiffness of aortic walls has been shown to be a marker of coronary and
      cerebrovascular diseases in patients with myocardial infarction or stroke.
      However, its value for predicting preclinical atherosclerosis has not been
      demonstrated. Therefore, this study tested the association of aortic wall
      stiffness and coronary and extracoronary atherosclerosis in the absence of
      clinical cardiovascular disease. In 190 asymptomatic men at cardiovascular risk,
      carotid-to-femoral pulse wave velocity (PWV) was measured mechanographically and
      the compliance of the aorta (C), as well as the intrinsic compliance (Ci), was
      deduced after correction for the effect of blood pressure. Also determined
      noninvasively were 1) the degree of coronary calcium deposit coded as grade 0, 1,
      2, or 3 using ultrafast computed tomography; 2) the extent of extracoronary
      plaque detected by B-mode echography at three different sites (carotid, abdominal
      aorta, and femoral) coded as 0, 1, 2, or 3 diseased sites; and 3) the estimated
      Framingham coronary risk. The grade of coronary calcium was not associated with
      any aortic elastic parameter. The number of extracoronary diseased sites was not
      associated with PWV and C but correlated negatively with Ci before but not after
      age adjustment. The coronary risk correlated positively with PWV and negatively
      with C before but not after age adjustment and was not associated with Ci. In
      symptom-free subjects aortic stiffening does not predict the presence of coronary
      and extracoronary atheroma and therefore cannot be considered as a useful
      surrogate marker of early atherosclerosis.

PMID- 9544870
TI  - Relationship between autonomic function and progression of renal disease in
      diabetic proteinuria: clinical correlations and implications for blood pressure
      control.
AB  - The objective of this study was to test the relationship between neurologic and
      microvascular complications of type 1 diabetes mellitus. It was hypothesized that
      the mechanisms operative in autonomic dysfunction seen in diabetic patients with
      microangiopathy play a role in the rapidity of progression to renal failure.
      Twenty-six type 1 diabetic patients with proteinuria were studied with
      computerized monitoring of heart rate variation during timed ventilation,
      assumption of upright posture, and Valsalva maneuver and with 24-h ambulatory
      blood pressure monitoring at baseline. Renal function was evaluated over the
      ensuing 12 months of intensive insulin therapy. Blood pressure was treated so as
      to achieve consistent 24-h readings < 140/90 mm Hg. Angiotensin converting enzyme
      inhibitors were the preferred antihypertensive agents. Serial serum creatinine
      concentrations were compared using repeated measures analysis of variance. Over
      12 months there were no significant serum creatinine changes for any autonomic
      test group with normal results at baseline. Groups with abnormal autonomic
      results at baseline demonstrated statistically significant increases in serum
      creatinine over 12 months compared to their baseline. Of the tests, Valsalva
      separated groups of patients with similar degrees of baseline renal impairment.
      Each of the sympathetic plus Valsalva combinations demonstrated a significant
      difference in progression of serum creatinine increase over 12 months. In each
      instance, if both sympathetic and Valsalva results were abnormal, there was a
      statistically significant increase in serum creatinine over 12 months when
      compared to groups in which one or both test results were normal. There is a
      relationship between autonomic function and the progression of renal dysfunction.
      The inability to vary the heart rate to a Valsalva maneuver identifies a degree
      of parasympathetic dysfunction that permits unopposed sympathetic tone, heralding
      more rapid renal destruction. A simple inexpensive bedside laboratory test
      discerned a relatively low-risk group of diabetic patients with proteinuria that
      demonstrated no deterioration in renal function over 12 months. When the Valsalva
      maneuver was markedly abnormal the presence of a mean arterial pressure > 100 mm
      Hg was associated with a greater likelihood of rapid renal deterioration. This
      group at higher risk of renal deterioration should undergo aggressive lowering of
      mean arterial blood pressure to < 95 mm Hg.

PMID- 9544872
TI  - Angiotensin II type 1 receptor gene polymorphism is associated with increase of
      left ventricular mass but not with hypertension.
AB  - A genetic epidemiologic approach is useful to elucidate the genes responsible for
      hypertension. Genetic analyses of the components of the renin-angiotensin system
      have succeeded in showing an association between their polymorphism and
      hypertension. Recently, two types of angiotensin II receptor were cloned and
      characterized. To examine the genetic contribution of angiotensin II type 1
      receptor (AT1) and type 2 receptor (AT2) genes in human essential hypertension, a
      case-control study was performed in Japanese subjects. The study comprised 321
      subjects with hypertension who satisfied the criteria for essential hypertension,
      together with 215 age and sex matched controls. The significance of the
      differences in genotype distribution between hypertensive and normotensive
      subjects was examined by chi2 analysis. Neither AT1 nor AT2 gene variants were
      associated with human essential hypertension in the Japanese subjects. However,
      the AT1 receptor gene polymorphism was associated with left ventricular mass
      index in normotensive subjects. The study results suggest that gene polymorphisms
      of both angiotensin II receptors are not directly involved in the increase of
      genetic risk for hypertension, but that the AT1 receptor gene might contribute
      genetically to the increase of left ventricular mass.

PMID- 9544871
TI  - The clinical utility of ambulatory blood pressure and heart rate monitoring in
      psychiatric inpatients.
AB  - Alterations in heart rate and blood pressure (BP) may occur in patients receiving
      psychiatric medication. Twenty-four-hour ambulatory blood pressure (ABP)
      monitoring was compared with nurses' conventional vital signs (CVS) for systolic
      (SBP) and diastolic (DBP) and heart rate (HR) measurements in psychiatric
      inpatients receiving multidrug treatments. Twelve consecutive subjects were
      enrolled. ABP monitoring and CVS measurements were concurrent but independent in
      each subject. Ambulatory BP monitoring recorded SBP, DBP, and HR thrice hourly
      from 6:00 AM to 10:00 PM and once hourly between 10:00 PM and 6:00 AM; CVS were
      obtained an average of 3.6 times/24 h. The frequency with which each BP and HR
      measurement method detected Level-1 (SBP 90 to 100 or 180 to 209 mm Hg; DBP 40 to
      60 or 110 to 119 mm Hg; HR 50 to 60 or 110 to 119 beats/min) or Level-2 (SBP < 90
      or > or = 210 mm Hg; DBP < 40 or > or = 120 mm Hg; HR < 50 or > or = 120
      beats/min) events was determined, and disagreements between the two measurement
      systems were analyzed using the McNemar test for paired sample data. Ambulatory
      BP monitoring detected significantly more Level-1 and Level-2 events than CVS. A
      significant number of mostly low BP were documented by ABP monitoring and were
      undetected by the CVS obtained by the nursing staff. This finding may be of
      clinical relevance in view of the potential hemodynamic consequences of
      hypotension, especially in older patients receiving psychotropic multidrug
      treatment.

PMID- 9544873
TI  - Effects of verapamil and trandolapril in the treatment of hypertension.
      Trandolapril Study Group.
AB  - The combination of an angiotensin converting enzyme inhibitor with a calcium
      antagonist has become a common way of treating patients with essential
      hypertension who respond insufficiently to monotherapy. This double-blind,
      randomized, parallel, placebo-controlled, multicenter, outpatient study evaluated
      the antihypertensive efficacy and safety of a calcium antagonist (verapamil SR)
      and an angiotensin converting enzyme inhibitor (trandolapril) in patients with
      mild-to-moderate (stages I and II) essential hypertension. Six hundred thirty-one
      patients were enrolled in this 10-week study. After a 4-week single-blind placebo
      phase, patients received one of the following daily dosage regimens in a double
      blind fashion for 6 weeks: placebo, 4 mg of trandolapril, 240 mg of verapamil SR,
      or a combination of 4 mg of trandolapril and 240 mg of verapamil SR. Trough
      sitting diastolic blood pressure was lowered by 4.5 mm Hg, 4.3 mm Hg, and 8.1 mm
      Hg more than placebo in the trandolapril, verapamil SR, and combination groups,
      respectively. In the combination group, sitting diastolic blood pressure was
      significantly lowered (P < .01) by 3.6 mm Hg more than in the trandolapril group
      and by 3.8 mm Hg more than in the verapamil SR group. An analysis of the trough
      to-peak ratio for sitting diastolic blood pressure revealed values of 0.75 and
      0.67, for the 4-mg trandolapril and the combination groups, respectively, at end
      point. The overall incidence of adverse reactions was similar for all treatment
      groups. In this study the combination of an angiotensin converting enzyme
      inhibitor and calcium antagonist was well tolerated and more effective than
      either agent administered alone for the treatment of mild-to-moderate essential
      hypertension.

PMID- 9544874
TI  - Cardiovascular-renal responses to long-term nitric oxide inhibition during
      angiotensin II-AT1 receptor inhibition.
AB  - A previous study in conscious dogs showed that the normal hypertensive response
      to short-term nitric oxide synthesis inhibition was markedly attenuated during
      angiotensin II-AT1 receptor inhibition. However, whether angiotensin plays an
      important cardiovascular role in the dog during long-term nitric oxide synthesis
      inhibition has not been determined and was therefore the goal of this
      investigation. Studies were conducted in 16 conscious dogs that received
      angiotensin AT1 receptor inhibition with L158809 (N = 8) or vehicle (N = 8) for
      12 d. During the last 6 d of this infusion, nitric oxide synthesis was inhibited
      by infusing NG-nitro-L-arginine methyl ester intravenously at 37.1 nmol/kg/min.
      In both the AT1 and vehicle groups, nitroarginine infusion significantly
      decreased the acetylcholine depressor response, glomerular filtration rate, renal
      plasma flow, and heart rate, and increased arterial pressure and renal vascular
      resistance in a similar manner, whereas it caused little change in the urinary
      excretion of sodium and water or in plasma renin activity. In conclusion, the
      long-term responses of arterial pressure, renal hemodynamics, and the renal
      excretion of sodium and water to nitric oxide synthesis inhibition were not
      significantly influenced by blockade of angiotensin AT1 receptors with L158809 in
      the dog.

PMID- 9544875
TI  - Alterations in membrane fatty acid unsaturation and chain length in hypertension
      as observed by 1H NMR spectroscopy.
AB  - Alterations in fatty acids of membrane phospholipids in essential hypertension
      may account for altered membrane ion transport, elasticity, and contractility
      properties of hypertensive tissues. To investigate the abnormalities in membrane
      fatty acids in essential hypertension, the degree of fatty acid unsaturation ([
      CH=CH-]/[-CH3]), the average carbon chain length, ratio of glycerol to fatty acyl
      chains, ratio of phosphatidylcholine to fatty acyl chains, and the ratio of free
      and acylated cholesterol to fatty acyl chains in fatty acid fractions of membrane
      phospholipids of aorta, kidney, and heart were determined in spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats by 1H nuclear magnetic
      resonance (NMR) spectroscopy. The degrees of fatty acid unsaturation in the aorta
      and the kidney membranes were significantly lower in SHR than in WKY rats (aorta,
      0.53+/-0.01 v 0.63+/-0.01, n = 5, P = .01; kidney, 0.70+/-0.01 v 0.84+/-0.03, n =
      10, P = .01). No significant difference could be detected in fatty acid
      unsaturation in heart membranes between these two strains. For aorta, kidney, and
      heart membranes, the average carbon chain lengths of fatty acid fractions of
      membrane phospholipids were significantly shorter for SHR than for WKY rats
      (aorta, 15.1+/-0.2 v 18.3+/-0.7, n = 5, P = .02; kidney, 14.5+/-0.2 v 16.4+/-0.4,
      n = 10, P = .01; heart, 17.3+/-0.5 v 18.8+/-0.6, n = 10, P = .05). The lower
      unsaturated fatty acid content in membrane phospholipids of the aorta and the
      kidney, with concomitant reduction in average chain length, may arise from
      increased oxidation of fatty acid double bonds in hypertensive tissues and may
      account, in part, for the increased aortic stiffness and abnormal kidney function
      associated with essential hypertension. Whether the lower unsaturated fatty acid
      content and decreased carbon chain length of phospholipid membranes in the aorta
      and the kidney are a cause or a consequence of the high blood pressure, however,
      remains unknown.

PMID- 9544876
TI  - Increased contraction of myocytes isolated from the young spontaneously
      hypertensive rat: relationship between systolic and diastolic function.
AB  - This study was designed to assess heart performance in young (10-week-old)
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, in terms of
      whole heart function in vivo and mechanics of isolated ventricular myocytes in
      vitro. The data suggest that left ventricular pressure (LVP) generation is
      greater, and the maximal velocities of LVP generation and decline are faster in
      SHR than in WKY. Two-dimensional morphologic measurements show that SHR myocytes
      are hypertrophied and that augmented contractile function is also present in
      isolated cells as determined by the extent of shortening and velocity of
      shortening. Relaxation is also faster at the myocyte level as determined by
      velocity of relengthening. However, the slope of the relationship between myocyte
      peak shortening and velocity of relaxation was similar in both groups. These
      results suggest that hyperdynamic myocyte relengthening may reflect changes in
      elastic recoil from increased shortening rather than intrinsic changes in
      cellular mechanisms, which are independent of shortening.

PMID- 9544877
TI  - Depressor role of angiotensin AT2 receptors in the (mRen-2)27 transgenic rat.
AB  - The (mRen-2)27 transgenic rat (Tg+), a hypertensive model dependent on increased
      expression of the renin angiotensin system, was used to explore the role of
      angiotensin AT2 receptors in the control of cardiovascular and renal excretory
      function. Experiments tested the effect of blockade of AT2 receptors on basal
      blood pressure and the pressor, renal excretory, and vasopressin (VP) responses
      to intravenous hypertonic saline (HS). Chronically catheterized male Tg+ and
      normotensive Sprague-Dawley rats (Tg-) were housed in metabolic cages. PD123319
      (AT2 antagonist) or 0.9% NaCl was given by intravenous bolus (3 mg/kg) followed
      by infusion (50 microg/kg/ min). Blockade of AT2 receptors both in Tg+ and Tg-
      rats produced no change in basal mean arterial pressure (MAP). The pressor
      response to intravenous HS (10% NaCl; 325 microL/100 g body weight) was
      significantly greater in Tg+ than in Tg- rats. PD123319 did not affect the peak
      rise in MAP but extended the time course of the response only in Tg+ rats. MAP
      was increased 39+/-4 and 36+/-3 mm Hg in Tg+ rats with and without the antagonist
      as compared to 20+/-2 and 24+/-2 mm Hg in Tg- rats. In the antagonist-treated Tg+
      rats, MAP remained elevated for 60 min as compared to 5 min for Tg+ control or Tg
      control or antagonist-treated rats. Hypertonic saline caused similar increases
      in plasma Na, VP, and in the natriuretic and diuretic responses in both Tg+ and
      Tg- rats, with no effect of antagonist treatment. These results demonstrate that
      Tg+ rats are sensitive to the effects of peripheral osmotic stimulation showing
      an increased pressor response, not attributed to greater secretion of VP or
      diminished natriuresis. These data also suggest that angiotensin AT2 receptors
      play a depressor role in the sodium-induced pressor response in this model.

PMID- 9544878
TI  - Effects of omapatrilat in low, normal, and high renin experimental hypertension.
AB  - Combined inhibition of neutral endopeptidase (NEP) and angiotensin converting
      enzyme (ACE) produces cardiovascular effects greater than those elicited by
      selective inhibition of either enzyme alone. Dual metalloprotease inhibitors are
      single molecules that inhibit both NEP and ACE and produce cardiovascular effects
      in animal models similar to those elicited by the combination of NEP and ACE
      inhibitors. The purpose of this study was to determined the duration of
      antihypertensive activity of the dual metalloprotease inhibitor omapatrilat in
      rodent models of hypertension. Omapatrilat inhibited NEP (Ki = 9 nmol/L) and ACE
      (Ki = 6 nmol/L) activities in vitro and inhibited the pressor response to
      angiotensin I in rats after intravenous administration with a potency and
      duration of action similar to those of the long acting ACE inhibitor
      fosinoprilat. After single dose administration, omapatrilat lowered mean arterial
      blood pressure (aortic catheter) in sodium depleted spontaneously hypertensive
      rats (high renin model) from 148+/-5 to 106+/-3 mm Hg (baseline to 24 h), in
      deoxycorticosterone acetate-salt hypertensive rats (low renin) from 167+/-4 to
      141+/-5 mm Hg and in spontaneously hypertensive rats (normal renin) from 162+/-4
      to 138+/-3 mm Hg (P < .05 at 24 h v vehicle in all models). After oral
      administration, omapatrilat (100 micromol/kg/day) persistently lowered systolic
      blood pressure (tail cuff) in spontaneously hypertensive rats during 11 days of
      treatment; at 24 h after dosing on day 12, mean arterial pressure (aortic
      catheter) was lower (P < .05) in the group receiving omapatrilat (133+/-5 mm Hg)
      than in the group receiving vehicle (149+/-2 mm Hg). The results indicate that
      omapatrilat is a potent dual metalloprotease inhibitor of NEP and ACE with long
      lasting, oral antihypertensive effects in low, normal, and high renin models of
      hypertension. Omapatrilat has the potential to be an effective, broad spectrum
      antihypertensive agent.

PMID- 9544879
TI  - Absence of endogenous circadian rhythmicity in blood pressure?
AB  - Currently available evidence reveals a predominant role of exogenous (so-called
      "masking") factors in the 24 h variation of blood pressure in humans. The
      existence of a (minor) endogenous circadian factor cannot be excluded, however.
      This possibility was tested by applying the rigorous unmasking conditions of the
      constant-routine protocol, that is, strict bed rest in a separate bedroom, total
      sleep deprivation, constant ambient temperature and illumination, and hourly
      equicaloric food and liquid intake. Twenty-five normotensive young individuals
      were subjected to a 26 h constant-routine procedure while hourly measurements
      were made of their blood pressure and heart rate. Repeated-measures analysis of
      variance failed to show a significant 24 h variation of blood pressure. The power
      of this test appeared satisfactorily high (>0.95). Heart rate, however, exhibited
      a significant circadian pattern, with a range of 6.7 beats/min (10% of the 24 h
      mean value). Moreover, the timing of the 24 h heart rate curves differed
      significantly between so-called morning (n = 10) and evening (n = 9) individuals.
      Mean peak values for the morning-types occurred at 11 AM, for the evening types
      nearly 6 h later. In conclusion, no evidence was found for the involvement of a
      circadian oscillator in the regulation of blood pressure.

PMID- 9544880
TI  - Antihypertensive drug treatment and fibrinolytic function.
AB  - Thromboembolic complications such as ischemic stroke and myocardial infarction
      are significantly more frequent in patients with arterial hypertension. From the
      available intervention studies, it appears that pharmacologic treatment of
      hypertension-at least with diuretics and beta-blockers-may more effectively
      protect against cerebrovascular as compared to coronary thromboembolic events.
      Whether other antihypertensive substances provide a more effective protection
      with respect to cardiac morbidity and mortality is the subject of numerous
      studies presently underway. These studies will help to answer the question of
      whether the extent of protection from coronary events during antihypertensive
      treatment depends on factors beyond blood pressure control. The fibrinolytic
      system is crucially involved in the pathogenesis of thromboembolic events. One
      determinant of this system is the balance between plasminogen activators (tissue
      type plasminogen activator [t-PA]) and inhibitors (plasminogen activator
      inhibitor 1 [PAI-1]). Experimental and clinical evidence suggests that at least
      some of the drugs used in the treatment of hypertension may alter the activity of
      the fibrinolytic system. Scarce and controversial data with respect to such an
      interaction exist with respect to diuretics, beta-blockers, and calcium
      antagonists. In addition, experimental evidence demonstrates that PAI-1 is
      stimulated by angiotensin II (A II), whereas t-PA is activated by bradykinin.
      Thus, antihypertensive drugs acting within the renin angiotensin system should
      exert effects also within the fibrinolytic system. However, results from clinical
      studies with angiotensin converting enzyme (ACE) inhibitors and A II receptor
      antagonists do not unequivocally support such a concept. The discrepancy in the
      results may, at least in part, be explained by studies performed in healthy
      volunteer subjects showing that ACE inhibition profoundly affected fibrinolysis
      only during stimulation of the renin angiotensin system by NaCL restriction.

PMID- 9544881
TI  - Regarding neonatal salt restriction.

PMID- 9544882
TI  - Children at increased risk for Wilms tumor: monitoring issues.

PMID- 9544883
TI  - Assessment of the respiratory status of infants and toddlers with cystic
      fibrosis.

PMID- 9544884
TI  - Inhaled steroids in children: risks versus rewards.

PMID- 9544885
TI  - Overweight and cholesterol elevation: which is the chicken and which is the egg?

PMID- 9544886
TI  - Dissecting the spectrum of fatty acid oxidation disorders.

PMID- 9544887
TI  - Bone mineral content in patients with short bowel syndrome: the impact of
      parenteral nutrition.

PMID- 9544888
TI  - Childhood cancer predisposition: applications of molecular testing and future
      implications.

PMID- 9544889
TI  - Risk of cancer during the first four years of life in children from The Beckwith
      Wiedemann Syndrome Registry.
AB  - To determine the incidence and relative risk (RR) of cancer in children with
      Beckwith-Wiedemann syndrome (BWS), children with BWS were followed up from birth
      until death, diagnosis of cancer, fourth birthday, or last day of follow-up. A
      total of 183 children with BWS were followed up for 482 person-years. The end
      points were incidence of cancer, RR of cancer, and RR associated with specific
      BWS phenotypic features. Thirteen children were identified with cancers before
      the fourth year of life in comparison with fewer than one cancer expected in this
      group on the basis of general population rates over the same period. The average
      annual incidence of cancer in the first 4 years of life was 0.027 cancer per
      person-year. The RR of Wilms tumor (RR = 816; 95% confidence interval [CI], 359
      1156), neuroblastoma (RR = 197; 95% CI, 22-711), and hepatoblastoma (RR = 2280;
      95% CI, 928-11,656) were statistically significant. Asymmetry of the limbs
      (hemihypertrophy) was the only clinical feature associated with an increased RR
      of cancer (RR = 4.6; 95% CI, 1.5-14.2). Given the high incidence of cancer in
      infancy and early childhood of patients with BWS, a prospective study is
      warranted to address the utility of screening for cancer.

PMID- 9544890
TI  - Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in
      Beckwith-Wiedemann syndrome.
AB  - OBJECTIVE: Beckwith-Wiedemann Syndrome (BWS) is an overgrowth syndrome associated
      with macrosomia, omphalocele, macroglossia, visceromegaly and Wilms tumor (WT).
      We conducted a case-control study in children with BWS to examine whether
      nephromegaly increases the risk of WT. METHODS: The BWS Registry was used to
      identify control and case patients. Control patients were defined as children
      with BWS who were older than 6 years and had no imaging evidence of renal disease
      or previous WT and for whom complete records were available; 31 patients met
      these criteria. Case patients were defined as children with BWS who had WT and
      screening renal imaging before the diagnosis of WT; 12 of these patients had
      serial screening images before diagnosis of WT and comprised the study
      population. Only renal images obtained before the diagnosis of WT was made were
      used to assess renal length. RESULTS: All 12 patients with WT had nephromegaly (>
      or =95th percentile of age adjusted renal length) on serial screening studies.
      Only four of 31 control patients (specificity = 86%) had nephromegaly resulting
      in an odds ratio of 72 (95% confidence interval = 13-391) for the risk of WT with
      nephromegaly. CONCLUSIONS: In patients with BWS, persistent nephromegaly is a
      strong risk factor for the development of WT. If screening for WT is done in this
      population, infants with nephromegaly should be considered those at greatest risk
      for WT, and screening may be best targeted at this group.

PMID- 9544891
TI  - Pulmonary function in hospitalized infants and toddlers with cystic fibrosis.
AB  - In older children with cystic fibrosis (CF), well-documented improvements in lung
      function occur during hospitalization for treatment of pulmonary exacerbations.
      OBJECTIVES: (1) To test the hypothesis that improvement in lung function occurs
      in infants and toddlers hospitalized because of CF pulmonary exacerbations. (2)
      To compare changes in lung function measured during forced expiratory flow and
      tidal breathing. STUDY DESIGN: Seventeen infants and toddlers with CF were
      evaluated at the beginning and end of hospitalization by the rapid thoracic
      compression technique to yield maximal flow at forced residual capacity. Tidal
      mechanics were measured by the esophageal balloon technique to yield lung
      conductance and compliance. RESULTS: Lung function improved during the course of
      hospitalization. The greatest change was observed in measurements of maximal flow
      at functional residual capacity (.VmaxFRC), increasing from 38.5% +/- 6%
      predicted (mean +/- SEM) to 59.8% +/- 6% at the end (p < 0.005). Lung conductance
      (GL) increased from 60% +/- 6% to 78% +/- 8% (p < 0.02); lung compliance (CL)
      increased from 66% +/- 5% to 75% +/- 5% (p < 0.03). The degree of improvement of
      .VmaxFRC, GL, and CL was related to baseline measurements; those with poorer
      pulmonary function at baseline had the greatest degree of improvement during
      hospitalization. CONCLUSION: Assessments of airflow obstruction from measurements
      of .VmaxFRC and GL do not necessarily demonstrate similar findings in a given
      infant with CF, perhaps because these two techniques measure different
      physiologic properties. Changes in .VmaxFRC may best reflect the predominant
      pathophysiology of lung disease in infants and toddlers with CF.

PMID- 9544892
TI  - Collagen metabolism and growth in prepubertal children with asthma treated with
      inhaled steroids.
AB  - OBJECTIVE: To investigate growth and markers of collagen and bone metabolism in
      prepubertal children with asthma. STUDY DESIGN: We measured growth velocity over
      12 months and markers of collagen types I and III synthesis (PINP, PICP, PIIINP),
      collagen type I degradation (ICTP), and bone metabolism (bone-specific alkaline
      phosphatase and osteocalcin) on one occasion in 56 prepubertal children with
      stable asthma, 39 of whom were treated with inhaled budesonide or beclomethasone.
      Collagen data were compared with normal control values. RESULTS: Children treated
      with inhaled steroids had reduced collagen synthesis (PINP, PIIINP) compared with
      control subjects (p = 0.038, p = 0.045), although PICP was increased (p = 0.05).
      Carboxyterminal telopeptide of type I collagen was reduced in patients treated
      with inhaled steroids (p < 0.0005) compared with nonsteroid-treated patients.
      Serum osteocalcin but not bone-specific alkaline phosphatase was significantly
      reduced in children treated with inhaled steroids (p < 0.02). Significant
      correlation was observed between PIIINP and ICTP and growth velocity. CONCLUSION:
      Collagen turnover is reduced in children with asthma receiving long-term inhaled
      steroid treatment. Markers of collagen synthesis provide a more accurate
      reflection of growth disturbance than osteocalcin and bone-specific alkaline
      phosphatase.

PMID- 9544894
TI  - Low total body bone mineral content and high bone resorption in Korean winter
      born versus summer-born newborn infants.
AB  - Seasonal differences in newborn total body bone mineral content (TBBMC) have not
      been studied, particularly in relation to alterations in vitamin D status in
      winter. In vitamin D deficiency bone resorption may be high and bone
      mineralization low. Bone resorption may be assessed by serum cross-linked
      carboxyterminal telopeptide of type I collagen (ICTP) measures. Because vitamin D
      supplements throughout pregnancy are uncommon in Korea, we hypothesized that in
      Korean winter newborns, TBBMC is low and serum ICTP high from high bone
      resorption and low 25-hydroxyvitamin D (25-OHD) compared with those in summer
      newborns. Seventy-one Korean term infants were studied prospectively in summer
      (July through September, n = 37) versus winter (January through March, n = 34);
      TBBMC was measured before 3 days of age by dual-energy x-ray absorptiometry.
      Significant seasonal differences were found: winter newborns had 6% lower TBBMC
      (least squares means +/- SD; 86.7 +/- 7.7 gm vs 93.9 +/- 7.8 gm, p = 0.0002),
      lower cord serum 25-OHD (10.7 +/- 8 nm vs 30 +/- 15 nm, p = 0.0001) and 1,25
      dihydroxyvitamin D, and higher ICTP (96.4 +/- 20.3 microg/L vs 74.8 +/- 24
      microg/L, p = 0.0002) and calcium than summer newborns. TBBMC correlated with
      serum 25-OHD (r = 0.243, p = 0.047) and inversely with ICTP (r = -0.333, p =
      0.008). We suggest that in Korea low maternal vitamin D status in winter results
      in marked reduction in newborn TBBMC.

PMID- 9544893
TI  - Age-related changes in cardiovascular disease risk factors of
      hypercholesterolemic children.
AB  - OBJECTIVE: To describe the age-related changes in cardiovascular disease risk
      factors in young, hypercholesterolemic (HC) children. METHODS:
      Hypercholesterolemic (n = 227) and nonhypercholesterolemic (NHC) (n = 80)
      children between the ages of 4 and 10 years were identified. Height, weight, skin
      fold and blood pressure measurements, and total cholesterol levels were measured.
      The HC group also had insulin levels evaluated. The groups were compared by
      analysis of variance. Simple Spearman correlations evaluated the associations
      between factors within each group. RESULTS: The HC and NHC groups had similar
      mean ages, heights, and weights, both contained 51% girls, and all were white
      subjects. Percent weight-for-height median, and biceps, triceps, suprailiac and
      subscapular skin-fold measurements were all larger for the HC group. A
      significant age interaction demonstrated that the HC group's larger suprailiac
      and sum of skin-fold measures were expressed in the 8.0- to 9.9-year-old
      children, but not the 4.0- to 5.9-year-olds. For both groups, systolic blood
      pressure was associated with the measures of adiposity. For the HC group, insulin
      levels were also associated with adiposity. CONCLUSIONS: These results suggest
      that: (1) children with HC have greater body fat, (2) the expression of the
      hypercholesterolemia precedes the expression of increased body fat, (3) body fat
      increases with age, and (4) altered insulin and blood pressure levels are
      expressed in association with the increased body fat in children with HC.
      Confirmation with longitudinal data is necessary.

PMID- 9544896
TI  - Regional cerebral blood flow during seizures in neonates.
AB  - With the use of 99mTc-D, L,-hexamethylpropylenamine oxime and single photon
      emission computed tomography, regional cerebral blood flow was measured ictally
      in 12 mature infants with recurrent seizures and compared with a reference group
      of nine interictal studies. The study indicates that both clinical and electrical
      seizures in neonates are associated with a focal cerebral hyperperfusion of the
      same amount as seen in adults.

PMID- 9544895
TI  - Feeding responses to free-flow formula in term and preterm infants.
AB  - OBJECTIVES: Although introducing freely flowing formula into the infant's mouth
      is a common feeding practice, its effect on feeding behavior is largely unknown.
      We evaluated the effects of free flow of formula from the nipple on infant
      feeding activity (sucking, swallowing, ingestion rate) and documented potential
      adverse behaviors such as cough, restless behavior, drooling, apnea, and
      bradycardia. METHODS: We studied 13 preterm and 7 term infants. During a feeding,
      bottle pressure was adjusted every 2 to 3 minutes to increase or decrease free
      flow from the nipple. RESULTS: Increase in free flow of formula from the nipple
      caused rapid increases in suck and swallow frequency in term and preterm infants
      and increased ingestion rate. The response was reversed by decreasing flow and
      was repeatable throughout the feeding. Peak suck and swallow rates were highest
      in term infants. Although drooling increased with increased milk flow, no effect
      of flow on coughing, restless behavior, or apnea was observed. CONCLUSIONS: Free
      flow formula is a potent stimulus for feeding activity in both preterm and term
      infants and is not associated with increased apnea or other adverse behaviors.
      The ability of the infant to divert excess formula flow by drooling is an
      efficient airway protective behavior. Reduced maximum suck and swallow frequency
      may be a primary basis for slow feeding in preterm infants.

PMID- 9544897
TI  - Relationship of uric acid concentrations and severe intraventricular
      hemorrhage/leukomalacia in the premature infant.
AB  - The purine metabolite hypoxanthine accumulates with hypoxia ischemia and with
      reperfusion is converted to uric acid (UA). We hypothesized that elevated UA
      concentration is a marker of previous hypoxia ischemia and would identify infants
      at greatest risk for having subsequent intraventricular hemorrhage
      (IVH)/periventricular leukomalacia (PVL). We determined the relationship between
      UA concentrations in the first postnatal day and the development of severe IVH,
      PVL, or both in 58 infants of birth weight 865 +/- 177 gm and gestational age 27
      +/- 2 weeks. Severe IVH developed in 10 (17%) infants and PVL in 3 (5.1%)
      infants. UA concentrations on day 1 (obtained at 16 +/- 4 hours) were 7.9 +/- 2.8
      mg/dl and increased to 9.5 +/- 2.58 mg/dl on day 2. UA concentrations on day 1
      were higher in infants with severe IVH/PVL versus those in infants with neither
      condition: 10.2 vs 7.3 mg/dl (p = 0.005). Infants with hyperkalemia on the second
      postnatal day had higher UA concentrations on the first day versus infants with
      normal potassium levels: 11.7 +/- 2 mg/dl versus 6.8 +/- 1.8 mg/dl (p < 0.0005).
      Infants with severe IVH/PVL had higher potassium levels on day 2 versus infants
      with neither condition: 11.9 vs 6.9 mg/dl (p < 0.048). By univariate analysis UA
      concentrations were significantly related to gestational age (p = 0.005) and
      birth weight (p = 0.03). Only UA concentration (p = 0.004) and gestational age (p
      = 0.02) were related to IVH/PVL. By multivariate analysis UA remained
      significantly related to IVH/PVL even when adjusted for other clinical variables,
      with an odds ratio estimate of 1.63 (95% confidence interval 1.16 to 2.31). In
      conclusion, higher UA concentrations on the first postnatal day were associated
      with the subsequent development of severe IVH/PVL and with subsequent
      hyperkalemia. Elevated UA concentrations in the first postnatal day may help to
      identify a subset of premature infants at greatest risk for having subsequent
      hemorrhagic ischemic injury.

PMID- 9544898
TI  - Chest physiotherapy may be associated with brain damage in extremely premature
      infants.
AB  - OBJECTIVES: To determine whether a characteristic form of brain damage
      (encephaloclastic porencephaly) was associated with chest physiotherapy treatment
      in preterm babies. METHODS: A retrospective case-control study was undertaken
      among 454 infants of birth weight less than 1500 gm cared for during the 3-year
      period of 1992 to 1994. Thirteen babies of 24 to 27 weeks of gestation who
      weighed 680 to 1090 gm at birth had encephaloclastic porencephaly. Twenty-six
      control subjects were matched for birth weight and gestation. RESULTS: The
      patients received two to three times as many treatments with chest physiotherapy
      in the second, third, and fourth weeks of life as did control infants (median 79
      vs 19 treatments in the first 4 weeks, p < 0.001). Patients also had more
      prolonged and severe hypotension in the first week than did control subjects
      (median duration of hypotension 4 vs 0.5 days, p < 0.01), and were less likely to
      have a cephalic presentation (31% vs 81%, p < 0.01). Since December 1994 no very
      low birth weight baby has received chest physiotherapy treatment in the first
      month of life in our nursery, and no further cases have occurred. CONCLUSIONS:
      Encephaloclastic porencephaly may be a previously unrecognized complication of
      chest physiotherapy in vulnerable extremely preterm infants.

PMID- 9544899
TI  - Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal
      infection.
AB  - OBJECTIVES: To determine whether neutrophil surface expression of CD11b predicts
      early-onset infection or suspected infection in at-risk infants. STUDY DESIGN:
      CD11b expression on peripheral blood neutrophils was determined by flow cytometry
      of whole blood samples. Blood (0.1 ml) was obtained from a convenience sample of
      at-risk infants admitted to the neonatal intensive care unit, stained with
      antibodies detecting CD11b and CD15, chilled, and analyzed within 8 hours. Blood
      for culture, blood counts, and C-reactive protein (CRP) determination was
      obtained simultaneously. Subjects were grouped on the basis of culture results
      and clinical signs, and investigators were blinded to CD11b level. RESULTS: Of
      106 subjects, seven had positive bacterial or viral cultures ("confirmed
      infection"), 17 had clinical signs of infection but negative cultures ("suspected
      infection"), and 82 had negative cultures and no clinical signs ("no infection").
      Neutrophil CD11b was elevated in all infants with confirmed infection, 94% with
      suspected infection, and none with no infection. The negative and positive
      predictive values, sensitivity, and specificity were 100%, 99%, 96%, and 100%,
      respectively, for diagnosis of neonatal infection at initial evaluation. CD11b
      levels correlated with peak CRP (r2 = 0.76, p < 0.0001); however, CD11b was
      elevated at the time of admission in all five infants with proven bacterial
      infection, whereas CRP was normal until the second day in the neonatal intensive
      care unit in three of these five. Both infants with positive viral cultures had
      elevated CD11b, but the CRP levels remained within normal limits. The negative
      predictive value of neutrophil CD11b for identifying suspected or confirmed
      infection was 99%. CONCLUSION: This assay for neutrophil CD11b is a promising
      test for exclusion of early-onset neonatal infection. If validated prospectively,
      this assay may reduce hospital and antibiotic use in the population of neonates
      at risk for early-onset infection.

PMID- 9544900
TI  - Decreased growth hormone response to glucagon in infants after an apnea of
      infancy.
AB  - We studied glucagon-induced growth hormone secretion in 9 patients with apnea of
      infancy and in 55 siblings of children who had died of sudden infant death
      syndrome, who were included as a comparison group. We observed a 33% decrease in
      growth hormone secretion in patients with apnea of infancy. However, linear
      growth remained normal. This finding could be related to either repeated episodes
      of hypoxia or to abnormal maturation of the autonomous nervous system.

PMID- 9544901
TI  - Growth hormone therapy with three dosage regimens in children with idiopathic
      short stature. European Study Group Participating Investigators.
AB  - OBJECTIVE: In children with idiopathic short stature (ISS) we studied the growth
      promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in
      three dose regimens and evaluated whether increasing the dosage after the first
      year could prevent a decline in height velocity (HV). DESIGN: Included were 223
      patients who were treated with subcutaneous administrations of rhGH 6 days per
      week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5
      IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter,
      corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively.
      Growth was compared with a standard of 229 untreated children with ISS [ISS
      standard]. RESULTS: During the first year of treatment HV almost doubled and was
      higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed
      among the groups, but increasing the dosage slowed the rate of the fall of HV.
      During 4 years of therapy the height SD score for age increased by a mean (SD) of
      2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased
      by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7).
      After 4 years the results of the group with 4.5 IU/m2 were slightly better than
      those of the other groups. When dropouts were included in the analysis (assuming
      a stable height SD score after discontinuation of rhGH therapy), height gain was
      still significant. CONCLUSIONS: During 4 years of rhGH therapy, growth and final
      height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to
      4.5 IU/m2. However, bone age advanced on average 4.8 years during this period;
      therefore, any effect on final height will probably be modest.

PMID- 9544902
TI  - Long-term growth and development in children after home parental nutrition.
AB  - Growth and development after the cessation of prolonged parenteral nutrition (PN)
      has not been fully evaluated. Growth, body composition, and nutritional and
      developmental status were documented in nine children (five boys, four girls) 2
      to 6 years old (mean 4.9 +/- 1.0 years) who had previously received long-term PN
      (mean 14.6 +/- 11.4 months). PN had been discontinued in all subjects for at
      least 6 months (mean 3.4 +/- 1.4 years); they were receiving oral feedings only.
      One subject had a significantly low height-for-age, and another had a low percent
      ideal body weight; five subjects had low total body fat. Serum vitamin A was low
      in six subjects. Seventy-two-hour fecal fat analysis was abnormal in two of eight
      subjects. Abnormal bone mineral density was present in four of nine subjects.
      Psychomotor development was normal in all nine subjects. Two had functional
      difficulties in swallowing. One or more abnormalities were present in all nine
      subjects. These findings suggest that children who require prolonged PN in early
      life are at risk for abnormalities in growth and nutritional status in later
      childhood; they require long-term dietary, growth, and nutritional monitoring.

PMID- 9544903
TI  - Plasma zinc status, growth, and maturation in children with sickle cell disease.
AB  - OBJECTIVE: The objective of this study was to determine the relation of plasma
      zinc (Zn) status to growth and maturation in children with SS genotype sickle
      cell disease. STUDY DESIGN: A cross-sectional study of 104 subjects who were 50%
      female and ranged in age from 0.4 to 18 years was performed. Measures included
      plasma Zn concentration (Znp), height, weight, skinfold thicknesses, elbow
      breadth, upper arm muscle area, and fat-free mass and fat mass by total body
      electrical conductivity. Skeletal maturation was assessed by hand-wrist x-ray
      evaluation and sexual maturation by Tanner stage. RESULTS: A total of 44% of the
      patients had low Znp (<10.7 micromol/L [70 microg/dl]); those with low Znp had
      significantly lower SD scores for height (p = 0.003), weight (p = 0.003), upper
      arm muscle area (p = 0.045), fat-free mass (p = 0.025), and elbow breadth (p =
      0.017) and greater skeletal maturation delay (p = 0.04). In older children (>9
      years) low Znp was associated with decreased Tanner scores for pubic hair (p =
      0.001) and breast and genital maturation (p = 0.009). No significant differences
      were seen in age, sex, or fat stores according to Zn status. CONCLUSIONS:
      Decreased plasma Zn is common in children with SS genotype sickle cell disease
      and is associated with decreased linear growth, skeletal growth, muscle mass, and
      sexual and skeletal maturation.

PMID- 9544904
TI  - Growth in asthmatic children treated with fluticasone propionate. Fluticasone
      Propionate Asthma Study Group.
AB  - OBJECTIVE: To determine whether inhaled fluticasone propionate has long-term
      effects on growth in children with persistent asthma. STUDY DESIGN: In a double
      blind, randomized, parallel-group, multicenter study, 325 prepubescent children
      with persistent asthma and normal growth rates were treated with placebo or
      inhaled fluticasone propionate powder 50 microg or 100 microg administered twice
      daily by a breath-actuated device for 1 year. Growth was evaluated monthly,
      whereas other safety variables and pulmonary function were evaluated
      periodically. RESULTS: The prepubescent patients showed no statistically
      significant differences in mean height, mean growth velocity, or mean skeletal
      age between any of the treatment groups at any time. Over a period of 1 year,
      mean height (+/- SE) increased 6.15 +/- 0.17 cm in the placebo group, 5.94 +/-
      0.16 cm in the fluticasone propionate 50 microg group, and 5.73 +/- 0.13 cm in
      the fluticasone propionate 100 microg group (p = 0.308, overall). CONCLUSIONS:
      Prepubescent children treated with fluticasone propionate 50 microg and 100
      microg administered twice daily for 1 year grew at rates similar to placebo
      treated control subjects and at rates equal to expected growth velocity for age.

PMID- 9544905
TI  - Growth status in children with cystic fibrosis based on the National Cystic
      Fibrosis Patient Registry data: evaluation of various criteria used to identify
      malnutrition.
AB  - OBJECTIVES: The objectives of this study were to determine growth status and to
      identify malnutrition with various anthropometric indicators in children with
      cystic fibrosis (CF) based on cross-sectional analysis of the 1993 National CF
      Patient Registry data. METHODS: Heights and weights of 13,116 children with CF
      were evaluated with percentile, percent of reference median, Z-score, and percent
      ideal weight-for-height based on National Center for Health Statistics/Centers
      for Disease Control growth references. Malnutrition was defined by four criteria:
      (1) height-for-age <5th percentile ("stunting") or weight-for-age <5th percentile
      ("wasting") (2) height-for-age <90% of reference median or weight-for-age <80% of
      reference median, (3) height-for-age <5th percentile or percent ideal weight-for
      height <85%, and (4) height-for-age <90% of reference median or weight-for-height
      <85% of reference median. RESULTS: Mean and median height- and weight-for-age
      were found to be at the 30th and 20th percentiles in children with CF.
      Malnutrition (height- or weight-for-age <5th percentile) was particularly
      pronounced in infants (47%) and adolescents (34%) and patients with newly
      diagnosed CF (44%). A significant sex difference (p < 0.01) in the occurrence of
      stunting (height-for-age <5th percentile) was observed during adolescence: boys
      11 to 14 years of age showed lower occurrence of stunting (19%) compared with
      girls (29%), whereas the opposite trend was observed at 15 to 18 years (34% in
      male patients vs 28% in female patients). CONCLUSION: Twenty percent of all
      children in the 1993 National CF Patient Registry were <5th percentile for height
      or weight-for-age. A significant discrepancy was found when different criteria
      were used to distinguish "stunting" versus "wasting" in malnourished children
      with CF.

PMID- 9544906
TI  - Nutrition intervention for weight gain in cystic fibrosis: a meta analysis.
AB  - OBJECTIVES: A meta analysis of the literature on treatment approaches to
      malnutrition in cystic fibrosis (CF) was conducted to evaluate the effectiveness
      of oral supplementation, enteral nutrition, parenteral nutrition, and behavioral
      intervention on weight gain before and after treatment. STUDY DESIGN: Eighteen
      studies were reviewed: four behavioral, six supplement, five enteral nutrition,
      and three parenteral nutrition. RESULTS: The weighted effect size for weight gain
      was large for each intervention: 1.51 behavioral, 1.62 oral, 1.78 enteral, and
      2.20 parenteral intervention. All interventions produced a large effect for
      weight gain in patients with CF. A univariate analysis of variance indicated no
      significant difference among the four interventions, F(3, 17) = 0.87, p > 0.05.
      Effect size for calorie intake was also evaluated when data were available (N = 7
      studies), yielding a sample size of three behavioral, two enteral, and two oral
      supplement studies. Analysis of variance indicated a significant effect for
      treatment, F(2,4) = 13.34, p < 0.05, with post hoc analysis indicating that the
      behavioral intervention had a greater effect size for calorie intake than oral
      supplement. CONCLUSIONS: All interventions were effective in producing weight
      gain in patients with CF. Behavioral intervention appeared to be as effective in
      improving weight gain in patients with CF as more invasive medical procedures.
      These findings support continued research on nutrition intervention with patients
      with CF including controlled clinical trials of the interventions and long-term
      follow-up on the impact of nutrition on disease progression.

PMID- 9544907
TI  - Acute pulmonary exacerbation is not associated with increased energy expenditure
      in children with cystic fibrosis.
AB  - OBJECTIVE: The objective of this study was to document alterations in resting
      energy expenditure (REE), energy intake, and body composition that occur during
      admission for management of a pulmonary exacerbation in children with cystic
      fibrosis. STUDY DESIGN: A prospective study of 14 children with cystic fibrosis
      (8 male, 12.5 +/- 3.3 years) was conducted throughout a 14-day hospitalization
      and again 3 weeks after discharge. Repeated measures analysis of variance was
      used to examine the change in variables across time. RESULTS: Significant
      increases were documented from days 1 to 14 in weight (37.1 +/- 13.1 kg to 38.4
      +/- 13.5 kg) and pulmonary function (forced expiratory volume in 1 second: 67.6%
      +/- 19.8% to 78.5% +/- 24.5%). Energy intake was not different between
      hospitalization and follow-up and averaged 175% of the Recommended Dietary
      Allowance. REE on day 1 was elevated (122% +/- 11% predicted); however, when
      expressed with fat free mass as a covariate, no significant changes were noted in
      REE throughout the eight measurements. CONCLUSIONS: These data suggest that an
      acute pulmonary exacerbation is not associated with an increase above a subject's
      baseline REE in children with cystic fibrosis with mild to moderate lung disease.
      Management of an acute pulmonary exacerbation should be associated with sustained
      improvement in pulmonary function and nutritional status; in contrast, weight
      loss or failure to improve pulmonary function should be seen as atypical.

PMID- 9544908
TI  - Symptoms of pervasive developmental disorders as observed in prediagnostic home
      videos of infants and toddlers.
AB  - OBJECTIVES: The objectives of this study were (1) to show prediagnostic
      abnormalities in social and communicative behaviors on home videos of children
      who later received a diagnosis of one of the pervasive developmental disorders
      (PDD) and (2) to demonstrate that prediagnostic abnormalities in social and
      communicative behaviors for children with PDD not otherwise specified will be
      less prominent than those in children with autistic disorder but still
      distinguishable from those of typically developing peers. STUDY DESIGN: Parents
      of children with PDD each submitted home videos of social events that were made
      when their child was between the ages of 12 and 30 months, before diagnosis. Two
      independent observers, unaware of the subjects' diagnoses or purpose of the
      study, scored the rates of specific anomalies in social and communicative
      behavior. Two additional observers scored the percentage of time the children
      were engaged socially or with objects. Data from the experimental group were
      compared with those of 25 age-matched children with no developmental
      disabilities. RESULTS: Significant differences were found between the rates of
      social engagement and 8 of the 25 specific behaviors of the children in whom PDD
      was later diagnosed and those of the typical children. The children later given
      the diagnosis of PDD not otherwise specified had mean frequencies of some social
      interactions and communicative skills that fell between those of children later
      given the diagnosis of autistic disorder and those of children with typical
      development. CONCLUSION: In our sample children in whom PDD was later diagnosed
      could be differentiated from their typically developing peers on the basis of
      specific anomalies noted in their social and communicative behaviors, especially
      joint attention. In our sample children with PDD not otherwise specified could
      have been further differentiated on the basis of the rates of social interaction.
      Careful assessment of social interaction and communicative behaviors may help to
      identify children with PDD before the age of 30 months.

PMID- 9544909
TI  - Presenting signs of retinoblastoma.
AB  - A retrospective chart review was performed on the charts of 1265 patients with
      retinoblastoma who were on file at New York Hospital and whose conditions had
      been diagnosed between the years 1960 and 1990. The mean follow-up was 90 months,
      ranging from 0 to 409 months. Thirty-two distinct presenting signs of
      retinoblastoma were identified, the most common of which were leukocoria (56.2%),
      strabismus (23.6%), poor vision (7.7%), and family history (6.8%). No correlation
      was found between any of the presenting signs and laterality, sex, race, or
      survival. Leukocoria correlated to Reese-Ellsworth Group Va or Vb, whereas
      strabismus was invariably associated with either macular tumors or macular
      retinal detachments. Eighty-three (96.5%) patients presenting with a family
      history did so before the age of 24 months. The presenting sign leading to a
      diagnosis of retinoblastoma was correlated with degree of advancement and tumor
      location. Leukocoria and strabismus are the most common presenting signs, with
      leukocoria correlated to more advanced disease and strabismus always associated
      with macular involvement. Vitreous hemorrhage (1 case, 0.1%), microphthalmos (4
      cases, 0.3%), and orbital cellulitis (3 cases, 0.2%) are extremely rare
      presenting findings in retinoblastoma.

PMID- 9544910
TI  - Risk factors for pediatric tuberculosis infection and disease after household
      exposure to adult index cases in Alaska.
AB  - OBJECTIVES: To determine risk factors for pediatric tuberculosis infection and
      active tuberculosis. STUDY DESIGN: We examined medical records from multiple
      sources for all 282 children younger than 15 years in Alaska during the period
      1987 to 1994 who were household contacts of an adult with culture-positive
      pulmonary tuberculosis. RESULTS: Infection developed in 25% of the children and
      progressed to active disease in 9.6%. Risk factors for pediatric infection
      included exposure to a parent who had active tuberculosis and exposure to any
      adult with active tuberculosis who had a cough, smear positivity, or a left upper
      lobe (LUL) chest lesion (odds ratios, 2.1 to 2.8). Among the 71 children in whom
      infection developed, Alaska Natives and younger children were more likely to
      progress to active tuberculosis, as were children exposed to a parent who had
      active tuberculosis and children exposed to any adult who had a LUL chest lesion
      (odds ratios, 1.5 to 12). CONCLUSIONS: Although all children with household
      exposure to adults with active tuberculosis have a high risk of contracting the
      infection and disease, specific risk factors can be identified and differ for
      infection and disease. Alaska Natives have an increased risk of progression to
      disease once infected.

PMID- 9544911
TI  - A patient with carnitine-acylcarnitine translocase deficiency with a mild
      phenotype.
AB  - Carnitine-acylcarnitine translocase deficiency, a rare beta-oxidation defect, is
      manifest in most cases by cardiomyopathy and death in early childhood. We report
      an affected patient, 3 years of age, who has had no serious complications. The
      residual enzyme activity in fibroblasts was higher than in previously reported
      patients, which may explain the benign clinical course.

PMID- 9544912
TI  - Bone mineral content in children with short bowel syndrome after discontinuation
      of parental nutrition.
AB  - To determine whether children with short bowel syndrome had evidence of metabolic
      bone disease, total body bone mineral content was measured by dual-energy x-ray
      absorptiometry in 18 patients and 36 age-, sex-, and race-matched control
      subjects. Children with short bowel syndrome had decreased bone mineral content
      compared with control subjects; however, it was not significant when adjusted for
      differences in weight and height. Whether these children will have normal bone
      accretion throughout puberty is not known.

PMID- 9544913
TI  - 3-Methylcrotonyl-coenzyme A carboxylase deficiency in Amish/Mennonite adults
      identified by detection of increased acylcarnitines in blood spots of their
      children.
AB  - Isolated 3-methylcrotonyl coenzyme A carboxylase (MCC) deficiency was documented
      in four adult women from the Amish/Mennonite population of Lancaster County,
      Pennsylvania. Metabolic and enzymatic investigations in these individuals were
      instituted after the detection of abnormal acylcarnitine profiles in blood spots
      obtained from their newborn children, in whom MCC activity was normal.

PMID- 9544914
TI  - Calibrated-orifice nipples for measurement of infant nutritive sucking.
AB  - To measure infant nutritive sucking reproducibly, nipple flow resistance must be
      controlled. Previous investigators have accomplished this with flow-limiting
      venturis, which has two limitations: flow resistance is highly dependent on fluid
      viscosity and older infants often reject the venturi nipple. This report
      describes the validation of calibrated-orifice nipples for the measurement of
      infant nutritive sucking. The flow characteristics of two infant formulas and
      water through these nipples were not different; those through venturi nipples
      were (analysis of variance; p < 0.0001). Flow characteristics did not differ
      among calibrated-orifice nipples constructed from three commercial nipple styles,
      indicating that the calibrated-orifice design is applicable to different types of
      baby bottle nipples. Among 3-month-old infants using calibrated-orifice nipples,
      acceptability was high, and sucking accounted for 85% of the variance in fluid
      intake during a feeding. We conclude that calibrated-orifice nipples are a valid
      and acceptable tool for the measurement of infant nutritive sucking.

PMID- 9544916
TI  - Increased risk of spastic diplegia among very low birth weight children after
      preterm labor or prelabor rupture of membranes.
AB  - Our objective was to study the association of spastic diplegia (SDP; N = 29) with
      the initiator of preterm birth in a regional cohort of 312 6-year-old very low
      birth weight children (< or =1500 gm). We determined the prevalence of SDP among
      those children born after idiopathic preterm onset of labor (POOL) or prelabor
      rupture of membranes (PROM) (12% SDP), and among those born after pregnancy
      induced hypertension or other medical indications for preterm delivery (4% SDP).
      Stratification showed that 83% of the children with diplegia were born after POOL
      or PROM. The threefold increased risk of SDP among those children born after POOL
      or PROM compared with the remainder of the cohort (crude odds ratio 3.2, 95%
      confidence interval 1.2 to 8.5) remained elevated after controlling for perinatal
      and neonatal variables (odds ratio 2.4 to 2.7) in logistic regression models. We
      conclude that birth after POOL or PROM increases the risk of SDP among very low
      birth weight children and speculate that this might be related to infectious
      processes leading to both POOL or PROM and SDP.

PMID- 9544915
TI  - Spastic diplegia as a complication of interferon Alfa-2a treatment of hemangiomas
      of infancy.
AB  - We report the development of spastic diplegia in infants during the course of
      interferon Alfa-2a (IFN) therapy for potentially life-endangering hemangiomas.
      Five infants who displayed diplegia were selected from a group of 26 infants
      treated with IFN. Diplegia persisted in three infants, and in the remaining two
      significant recovery occurred after IFN was discontinued. Magnetic resonance
      imaging showed no significant brain or spinal abnormalities except minor to
      moderate delayed myelination in two patients. Myelination was normal on
      subsequent radiographic examination in all five patients. We conclude that IFN
      can adversely affect the immature central nervous system and produce spastic
      diplegia, which is potentially reversible. We recommend careful clinical
      assessment of neurodevelopmental status during IFN therapy.

PMID- 9544917
TI  - Successful treatment of a staphylococcal endocarditis vegetation with tissue
      plasminogen activator.
AB  - A 930 gm premature infant had Staphylococcal endocarditis with a tricuspid
      valvular vegetation that was unresponsive to antibiotics and not amenable to
      resection. Infusion of tissue plasminogen activator over a 3-day period
      completely lysed the vegetation. The infection cleared with continued
      antibiotics, and the infant recovered without sequelae.

PMID- 9544918
TI  - Recurrent group B streptococcal disease in infants: Who should receive rifampin?
AB  - A preterm breast-fed infant had three episodes of type Ia/c group B streptococcus
      septicemia. After the second episode rifampin was given to the infant, but
      further Ia/c exposure to maternal breast milk ensued. We propose rifampin
      treatment for both the mother and infant in cases of recurrent group B
      streptococcus disease.

PMID- 9544919
TI  - Acute eosinophilic pneumonia: a cause of reversible, severe, noninfectious
      respiratory failure.
AB  - We report a case of acute eosinophilic pneumonia associated with adult
      respiratory distress syndrome in an adolescent. This entity should be considered
      in the differential diagnosis in previously well children and adolescents who are
      seen with unexplained respiratory failure and who have many eosinophils in
      bronchoalveolar lavage fluid. Prompt recognition of this rapidly reversible
      noninfectious disorder and institution of corticosteroids may be lifesaving.

PMID- 9544920
TI  - A pilot study of combination therapy with indinavir, stavudine (d4T), and
      didanosine (ddI) in children infected with the human immunodeficiency virus.
AB  - Twelve children infected with the human immunodeficiency virus were treated
      orally with indinavir, stavudine, plus didanosine for 12 to 48 weeks. Therapy was
      limited in some cases by nonadherence, intolerance, toxicity, and virologic
      failure. Marked increases in CD4+ lymphocyte counts and decreases in plasma human
      immunodeficiency virus RNA concentrations suggest that the regimen has potent
      antiviral activity.

PMID- 9544921
TI  - Pneumatosis intestinale in children with primary combined immunodeficiency.
AB  - We report six episodes of pneumatosis intestinale (PI) in children with primary
      combined immunodeficiency. PI was generally benign and responded to conservative
      therapy. Increased risk of infection or disruption of gastrointestinal mucosa are
      probable predisposing factors. A diagnosis of PI should be considered in children
      with primary combined immunodeficiency who experience otherwise unexplained
      gastrointestinal symptoms, particularly in the early post-transplant period.

PMID- 9544922
TI  - Profound neonatal congestive heart failure caused by maternal consumption of blue
      cohosh herbal medication.
AB  - A newborn infant whose mother ingested an herbal medication, blue cohosh, to
      promote uterine contractions presented with acute myocardial infarction
      associated with profound congestive heart failure and shock. The infant remained
      critically ill for several weeks, although he eventually recovered. Other causes
      of myocardial infarction were carefully excluded. Blue cohosh, Caulophyllum
      thalictroides, contains vasoactive glycosides and an alkaloid known to produce
      toxic effects on the myocardium of laboratory animals. We believe this represents
      the first described case of deleterious human fetal effects from maternal
      consumption of blue cohosh.

PMID- 9544923
TI  - Pediatric imaging perspective: acute head trauma--Is skull radiography useful?

PMID- 9544924
TI  - Purpura fulminans skin lesions in a newborn with complete protein C deficiency.

PMID- 9544925
TI  - Osteogenesis imperfecta: Are fractures and growth hormone treatment linked?

PMID- 9544926
TI  - Oral feeding in low birth weight infants.

PMID- 9544927
TI  - Spectrum of the X-linked hyper IgM syndrome.

PMID- 9544928
TI  - Cyclization of alpha-aminoadipic acid into the the delta-lactam 6-oxo-piperidine
      2-carboxylic acid by Penicillium chrysogenum.

PMID- 9544929
TI  - TMC-49A, a novel transcriptional up-regulator of low density lipoprotein
      receptor, produced by Streptomyces sp. AS1345.
AB  - Microbial metabolites were screened for a transcriptional up-regulator of low
      density lipoprotein (LDL) receptor by a reporter assay. TMC-49A was discovered as
      an up-regulator obtained from the fermentation broth of Streptomyces sp. AS1345.
      The structure of TMC-49A was elucidated to be butyl N-phenethylcarbamate by
      spectroscopic analyses. This compound enhanced the synthesis of LDL receptor in
      human hepatoma HepG2 cells as assessed by a receptor binding assay. Taxonomy of
      the producing strain is also described.

PMID- 9544930
TI  - CJ-12,373, a novel topoisomerase II inhibitor: fermentation, isolation, structure
      elucidation and biological activities.
AB  - A novel isochroman carboxylic acid CJ-12,373 was isolated from Penicillium sp.
      CL22557. CJ-12,373 inhibits both DNA gyrase-mediated supercoiling and relaxation
      without the formation of a cleavage intermediate, suggesting that CJ-12,373
      inhibits DNA gyrase at a stage distinct from the religation step. CJ-12,373 is
      not selective for procaryotic DNA gyrase as it also inhibits relaxation mediated
      by eukaryotic topoisomerase II. The antimicrobial potency of CJ-12,373, however,
      is largely attributed to its inhibition of DNA gyrase.

PMID- 9544931
TI  - Glisoprenins C, D and E, new inhibitors of appressorium formation in Magnaporthe
      grisea, from cultures of Gliocladium roseum. 1. Production and biological
      activities.
AB  - Glisoprenins C, D, and E, new glisoprenin derivatives, were isolated together
      with glisoprenin A from submerged cultures of the deuteromycete Gliocladium
      roseum HA190-95. All glisoprenins inhibited appressorium formation in Magnaporthe
      grisea on inductive (hydrophobic) surfaces. The compounds exhibited moderate
      cytotoxic, but no antifungal, antibacterial or phytotoxic activities.

PMID- 9544932
TI  - Cremimycin, a novel 19-membered macrocyclic lactam antibiotic, from Streptomyces
      sp.
AB  - A novel 19-membered macrocyclic lactam antibiotic, cremimycin, was isolated from
      the culture broth of an actinomycete strain. The producing organism, designated
      MJ635-86F5, was identified as a member of Streptomyces. Cremimycin was isolated
      from the mycelial cake by extraction with CHCl3-MeOH and precipitation with
      hexane-MeOH. The structure of cremimycin was determined by spectroscopic study.
      Cremimycin showed broad antimicrobial activities against Gram-positive bacteria
      including MRSA.

PMID- 9544933
TI  - Nothramicin, a new anthracycline antibiotic from Nocardia sp. MJ896-43F17.
AB  - A new antibiotic designated nothramicin was isolated from the culture broth of
      Nocardia sp. MJ896-43F17 which was closely related to Nocardia brasiliensis. It
      was isolated by the Diaion HP-20 column chromatography, butyl acetate extraction
      and purified by HPLC. It inhibited the growth of mycobacteria at the
      concentration of 1.56 approximately 25 microg/ml. Nothramicin was revealed to be
      a new member of anthracycline antibiotics by the various spectroscopies.

PMID- 9544934
TI  - In vitro microbiological characterization of novel macrolide CP-163,505 for
      animal health specific use.
AB  - A novel 16-membered-ring macrolide agent (CP-163,505, a reductive amination
      derivative of repromicin) was identified as an antibacterial against Pasteurella
      haemolytica, P. multocida and Actinobacillus pleuropneumoniae, important
      etiological agents of livestock respiratory disease. In vitro MIC50/90 analysis
      revealed that CP-163,505 was more potent (4x) than tilmicosin against P.
      multocida, and equivalent to tilmicosin against P. haemolytica and A.
      pleuropneumoniae. In time kill kinetic studies, CP-163,505 showed bactericidal
      activity against P. haemolytica, P. multocida and A. pleuropneumoniae and
      bacteriostatic activity against E. coli at 8 times its MIC. In vitro, CP-163,505
      was more potent in alkaline pH (16 approximately 32 x ) and less potent in the
      presence of excess cations (Mg+2 and Ca+2, 4x). EDTA and PMBN increased CP
      163,505 potency against E. coli (4x) but not against the other species. Similar
      results were obtained with erythromycin A and tilmicosin, which were used as
      controls. From our data, we hypothesize that Pasteurella and Actinobacillus have
      an outer membrane significantly different from that of the typical enteric Gram
      negative bacterium E. coli.

PMID- 9544935
TI  - New quinolone compounds from Pseudonocardia sp. with selective and potent anti
      Helicobacter pylori activity: taxonomy of producing strain, fermentation,
      isolation, structural elucidation and biological activities.
AB  - Eight novel quinolones with anti-Helicobacter pylori activity were isolated from
      the actinomycete Pseudonocardia sp. CL38489. The quinolones were very potent
      against H. pylori with MICs up to 0.1 ng/ml. The quinolones appear to be specific
      for H. pylori, since they did not show antimicrobial activity when tested against
      a panel of other microorganisms.

PMID- 9544936
TI  - Antimalarial activity of radicicol, heptelidic acid and other fungal metabolites.
AB  - In the course of our screening program for artemisinin-like antimalarial
      compounds from microorganisms, seven fungal metabolites such as radicicol and
      heptelidic acid were identified as active compounds. Some of them exhibited
      antimalarial activity in vitro against the human malaria parasite Plasmodium
      falciparum to the extent of approximately 1/10 as potent as artemisinin.
      Radicicol was moderately active in vivo against Plasmodium berghei in mice.

PMID- 9544937
TI  - Development of an improved cloning vector and transformation system in
      Amycolatopsis mediterranei (Nocardia mediterranei).
AB  - A versatile plasmid cloning vector pRL60 carrying kanamycin/neomycin resistance
      (km/neo), erythromycin resistance (ermE) and alpha-amylase (alpha-amy) marker
      genes that replicates in various Amycolatopsis mediterranei strains and
      Escherichia coli has been constructed. This cloning vector has been derived from
      a hybrid plasmid pRL50, which was developed by cloning ermE from pIJ4026 into a
      pRL1 derivative pULAM2. While cloning ermE into the BamHI site of pULAM2, only a
      hybrid plasmid pRL50 with an additional copy of pULAM2 was selected. Thus pRL50
      (18.7 kb) contained two copies each of the km/neo, alpha-amy, and one copy of
      ermE. When pRL50 was transformed into A. mediterranei DSM 40773 through
      electroporation and selected under erythromycin resistance, the plasmid underwent
      a spontaneous deletion of 8.5 kb fragment resulting in the formation of plasmid
      pRL60. pRL60 (10.2 kb) is a shuttle vector between A. mediterranei and E. coli
      with three marker genes: km/neo, ermE and alpha-amy. ermE is expressed in A.
      mediterranei thus allowing good selection of transformants. The alpha-amy gene of
      pRL60 is also expressed in A. mediterranei DSM 40773 and its activity can be
      easily detected on starch containing medium after iodine staining. Most critical
      parameters evaluated for electrotransformation using pRL60 in A. mediterranei
      were growth phase, electrical field strength, pulse length, pretreatment of
      mycelia with lysozyme and use of salt free water. At optimized parameters, a
      transformation efficiency of 4.0 x 10(4) transformants/microg DNA was
      reproducibly achieved for A. mediterranei DSM 40773. pRL60 could also be
      transformed into A. mediterranei DSM 43304, DSM 46095, MTCC-17 and in mutants
      F1/24 and T-195, (derived from an industrial strain of A. mediterranei N813). The
      alpha-amy of pRL60 conferred an amylolytic phenotype to all these strains. With
      the development of pRL60 and a reproducible transformation protocol, the
      application of recombinant DNA techniques to these industrial microorganisms has
      now become feasible.

PMID- 9544938
TI  - Directed biosynthesis of peptaibol antibiotics in two Trichoderma strains. I.
      Fermentation and isolation.
AB  - Peptaibols are linear alpha-aminoisobutyric acid-containing peptide antibiotics
      originating from soil fungi mainly of the genus Trichoderma and biosynthesized in
      complex mixtures of closely related analogues by a polyenzymatic pathway.
      Addition of amino acids such as alpha-aminoisobutyric acid (Aib), glutamic acid
      or arginine, to the fermentation medium of two Trichoderma strains, T. harzianum
      and T. longibrachiatum, has been shown to result in the simplification of the
      natural peptaibol mixtures, leading in each case to the almost exclusive
      biosynthesis of a single peptide. Surprisingly, the obtained peptides are Aib
      enriched, whether the added amino acid is Aib, Glu or Arg. By adding Aib to the
      fermentation medium of T. harzianum, two new Aib-rich peptaibols were isolated.
      Moreover, adding glutamic acid to the culture medium of T. longibrachiatum, which
      produces both neutral and acidic 20-residue peptaibols with either glutamine or
      glutamic acid at position 18, increases the production of the acidic peptides.
      However, arginine which is a positively charged amino acid generally absent from
      peptaibol sequences, is not incorporated in trichorzins when added to the
      fermentation medium of T. harzianum.

PMID- 9544939
TI  - Directed biosynthesis of peptaibol antibiotics in two Trichoderma strains. II.
      Structure elucidation.
AB  - Alpha-aminoisobutyric acid-directed biosynthesis in two Trichoderma strains has
      been shown to lead to the simplification of the natural peptaibol
      microheterogeneous mixtures and to the production of new analogues. Hence, two
      new peptides originating from T. harzianum, trichorzin PA(U) 4 and harzianin PCU
      4, were isolated by HPLC. Their sequences were determined by positive liquid
      secondary-ion mass spectrometry (LSI MS). Trichorzin PA(U) 4 and harzianin PC(U)
      4 are 18- and 14-residue peptaibols, respectively, both containing a high
      proportion of alpha-aminoisobutyric acid (Aib). LSI MS performed with lithium
      cationized peptides, allowed to assign the relative position of
      leucine/isoleucine isomeric residues, even without the use of tandem mass
      spectrometry.

PMID- 9544940
TI  - Synthesis and activities of bactobolin derivatives based on the alteration of the
      functionality at C-3 position.
AB  - Some derivatives of bactobolin were prepared from bactobolin (1) by radical
      reduction and formation of the fused azetidine ring. The derivatives proved less
      active than the parent antibiotic 1 against bacteria, indicating that
      dichloromethyl group at C-3 position play an important role in biological
      activity.

PMID- 9544941
TI  - Synthesis and antimicrobial evaluation of TAN-1057A/B analogs.
AB  - TAN-1057A-D, dipeptides isolated from bacteria Flexibacter sp. PK-74 and PK-176,
      are new antibiotics with potent antibacterial activity against methicillin
      resistant Staphylococcus aureus (MRSA). We describe, in detail, the synthesis of
      several TAN-1057A/B analogs by a convergent route featuring a new method to
      construct the cyclic amidinourea functional group. The biological activity of
      these substances against methicillin-resistant Staphylococcus aureus (MRSA) is
      reported.

PMID- 9544942
TI  - Synthesis and activity of 3-epi-actinobolin.
AB  - 3-epi-Actinobolin was synthesized by the chemical transformation of actinobolin
      involving a key step of the reconstruction of fused delta-lacton skeleton via
      intramolecular acylation reaction. The analogue with low toxicity weakly inhibits
      Gram-positive and Gram-negative bacteria.

PMID- 9544944
TI  - Sch 40832: a novel thiostrepton from Micromonospora carbonacea.

PMID- 9544943
TI  - Novel C-2 substituted carbapenem derivatives. Part IV. Synthesis and biological
      activity of five membered heteroaromatic derivatives.
AB  - The synthesis, antibacterial activity, and stability to human dehydropeptidase-1
      (DHP-1) of a novel series of (5R,6S)-6-[(1R)-1-hydroxyethyl]-2
      heterocyclylcarbapen-2-em-3-carb oxylates are described. Of the compounds
      investigated 1,5-disubstituted pyrazol-3-yl and 3-substituted isoxazol-5-yl
      derivatives have the best combination of antibacterial activity and stability to
      DHP-1. They are particularly active against community-acquired respiratory tract
      pathogens and have stabilities to DHP-1 superior to that of meropenem.

PMID- 9544945
TI  - Biosynthetic studies on the alpha-glucosidase inhibitor acarbose in Actinoplanes
      sp.: glutamate is the primary source of the nitrogen in acarbose.

PMID- 9544946
TI  - Glisoprenins C, D and E, new inhibitors of appressorium formation in Magnaporthe
      grisea, from cultures of Gliocladium roseum. 2. Structure determination.

PMID- 9544947
TI  - Structure of ericamycin having a 2-azahexaphene ring system.

PMID- 9544948
TI  - Studies on the cytotoxicity of asterriquinone derivatives.

PMID- 9544949
TI  - The synthesis and antifungal activity of nitrogen containing hemiaminal ethers of
      LY303366.

PMID- 9544950
TI  - Will xenotransplantation ever be feasible?
AB  - In several recent conferences, the principal questions have been whether
      xenotransplantation technology should be encouraged and, if so, how it should be
      regulated. Because the prospect of successful transplantation of animal organs
      into humans is still remote, the rush to achieve consensus about clinical
      application would be inexplicable were it not for two ostensibly unrelated
      issues. The first is the small but undeniable theoretical hazard of causing new
      human infections with the intermingling of tissues from different species. The
      second, advanced by animal-rights advocates, concerns the spiritual and ethical
      relationship of humans to animals.

PMID- 9544951
TI  - Genetic therapies for xenotransplantation.

PMID- 9544952
TI  - The dialectic nature of xenotransplantation.

PMID- 9544953
TI  - En bloc transplantation of infant kidneys: ten-year experience.
AB  - BACKGROUND: Recent data have shown that en bloc infant kidneys transplanted to
      adult recipients functioned well. Longterm graft survival and function are not
      available, however. This study analyzes the 10-year experience with
      transplantation of en bloc infant kidneys from 1987-1997. STUDY DESIGN: This is a
      chart review of adult recipients of en bloc infant kidneys with respect to
      donors' and recipients' age, weight, creatinine, HLA antigen matching, panel
      reactive antibodies, cold ischemia time, surgical complications, original
      disease, and longterm graft function and survival. RESULTS: Five en bloc kidneys
      thrombosed (6.4%). Two ureteral fistulas were repaired successfully. Five
      patients underwent dialysis (6.4%). Two patients died of infection, six of heart
      attack and stroke, and one of cancer. All had excellent graft function at
      patients' death. Renal artery stenosis was dilated in seven patients. Six grafts
      were lost to rejection (one from noncompliance at 20 months). The original
      disease recurred in three patients with massive proteinuria despite excellent
      function. Graft survival at 43 months (range, 6-123 months) was 79%, with serum
      creatinine levels at 1, 3, 9 and 10 years of 1.2, 1.0, 0.8 and 0.8 mg/dl,
      respectively. Creatinine clearance averaged 88 mL/min (range, 34-188 mL) and 24
      hour proteinuria was 146 mg (normal range, 10-150). CONCLUSIONS: In conclusion,
      en bloc infant kidneys can be transplanted successfully with excellent longterm
      function, hyperfiltration injury was not observed, and infant kidneys should be
      used more frequently.

PMID- 9544954
TI  - Intraoperative endovascular angioplasty and stenting of iliac artery: an adjunct
      to femoro-popliteal bypass.
AB  - BACKGROUND: With the rapid development of endovascular techniques, the management
      strategy of patients with multilevel atherosclerotic arterial occlusive disease
      is also evolving. Iliac artery stenting is a means whereby multiple bypass
      operations can be avoided in such patients. The early results of preoperative
      iliac artery stenting seem promising but the role of intraoperative iliac artery
      angioplasty and stenting is less clear. STUDY DESIGN: This study was undertaken
      to evaluate our early results of a combined endovascular and operative approach
      to patients with multilevel atherosclerotic arterial occlusive disease. Between
      June 1995 and March 1997, primary intraoperative iliac artery balloon angioplasty
      and stent placement were performed on 13 affected limbs of 12 patients undergoing
      an infrainguinal bypass operation. Indications for operation, patient
      demographics, and risk factors were noted. The outcome of surgery and the patency
      rates of bypass graft and stent were also recorded. RESULTS: The initial
      technical success of primary iliac artery angioplasty and stenting was 93%. An
      improvement of the ankle-brachial index by a mean value of 0.38 was attained
      after operation (p < 0.001). Clinical success, based on the criteria suggested by
      the Society for Vascular Surgery/International Society for Cardiovascular
      Surgery, was achieved in all patients. There was no operative or hospital
      mortality. Postoperative morbidity rate was 8% (n = 1). The cumulative 1-year
      patency rates of iliac stent and infra-inguinal bypass grafts were 100% and 85%,
      respectively. The limb loss rate was 7%. CONCLUSIONS: The technique of
      intraoperative angioplasty and stenting can be easily mastered by an experienced
      and skilled vascular surgeon, using a portable C-arm fluoroscopic unit, in the
      operation theater. A combined endovascular and operative approach optimizes the
      therapeutic option to this selected group of patients.

PMID- 9544955
TI  - A comparative analysis of lobular and ductal carcinoma of the breast:
      presentation, treatment, and outcomes.
AB  - BACKGROUND: Compared with invasive ductal carcinoma, invasive lobular carcinoma
      of the breast is considered by many to be a more indistinct and multicentric form
      of cancer that is detected later and is treated less optimally by breast
      preservation techniques. This study analyzed the presentation, treatment trends,
      and survival rates of women who had invasive lobular and ductal breast carcinoma.
      The objective was to determine the utility of breast-preservation therapy for
      invasive lobular carcinoma by analysis of historic data on tumor features and
      survival. STUDY DESIGN: Data on 291,273 women diagnosed with invasive carcinoma
      between 1985 and 1993 were obtained from the National Cancer Data Base. Analysis
      included the patient's age at diagnosis; tumor histology, anatomic site,
      diameter, grade, and stage; treatment; and disease status 5 years after
      diagnosis. RESULTS: The mean patient age at diagnosis was 61.0 years for invasive
      ductal carcinoma, 63.0 years for invasive lobular carcinoma, and 60.6 years for
      tumors with combined histology. The anatomic location, tumor diameter, and tumor
      grade were similar for each histotype. Breast-preservation therapy was less
      frequent for invasive lobular carcinoma. The 5-year overall survival and local
      disease-free survival rates for women treated with breast preservation were
      similar for invasive ductal carcinoma (84% overall survival; 97% disease-free
      survival) and invasive lobular carcinoma (87% overall survival; 98% disease-free
      survival). CONCLUSIONS: Invasive lobular carcinoma presents with a similar age
      distribution, anatomic subsite, diameter, and grade as invasive ductal carcinoma.
      Breast preservation is selected less commonly for women who have invasive lobular
      carcinoma, but this choice of therapy does not compromise the disease-free or
      overall survival status of this group of patients.

PMID- 9544956
TI  - Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan
      Kettering Cancer Center.
AB  - BACKGROUND: Sentinel node biopsy (SNB) has emerged as a potential alternative to
      routine axillary dissection in clinically node-negative breast cancer. STUDY
      DESIGN: From September 1995 to June 1996 at Memorial Sloan-Kettering Cancer
      Center, 60 patients with clinically node-negative cancer underwent SNB, which was
      immediately followed by standard axillary dissection. Both blue dye and
      radioisotope were used to identify the sentinel node. SNB was compared with
      standard axillary dissection for its ability to accurately reflect the final
      pathologic status of the axillary nodes. RESULTS: The sentinel node was
      successfully identified by lymphoscintigraphy in 75% (42 of 56), by blue dye in
      75% (44 of 59), by isotope in 88% (52 of 59), and by the combination of blue dye
      and isotope in 93% (55 of 59) of all 59 evaluable patients. Of the 55 patients in
      this study where sentinel nodes were identified, 20 (36%) were histologically
      positive. The sentinel node was falsely negative in three patients, yielding an
      accuracy of 95%. SNB was more accurate for T1 (98%) than for T2-T3 tumors (82%).
      CONCLUSIONS: Lymphatic mapping is technically feasible, reliably identifies a
      sentinel node in most cases, and appears more accurate for T1 tumors than for
      larger lesions. Blue dye and radioisotope are complementary techniques, and the
      overall success of the procedure is maximized when the two are used together.

PMID- 9544957
TI  - Laparoscopic repair of paraesophageal hiatal hernias.
AB  - BACKGROUND: Regardless of symptoms, paraesophageal hiatal hernias should be
      repaired in order to prevent complications. This study reports the University of
      California San Francisco experience with laparoscopic repair of paraesophageal
      hiatal hernias, emphasizing the technical steps essential for good results.
      PATIENTS AND METHODS: From May 1993 to September 1997, 55 patients, 27 women and
      28 men, with a mean age of 67 years (range, 35-102 years) underwent laparoscopic
      repair of paraesophageal hernias at the University of California San Francisco.
      Symptoms, which had been present an average of 85 months before surgery,
      consisted mainly of pain (55%), heartburn (52%), dysphagia (45%), and
      regurgitation (41%). Of the four patients who presented with acute illness, two
      had gastric obstruction, one had severe dyspnea, and one had gastric bleeding.
      Endoscopy demonstrated esophagitis in 25 (69%) of 36 patients, and 24-hour pH
      monitoring demonstrated acid reflux in 22 (67%) of 33 patients. Manometry
      detected severely impaired distal esophageal peristalsis in 17 (52%) of 33
      patients. The preferred operation consisted of reduction of the hernia, excision
      of the sack and the gastric fat pad, closure of the enlarged hiatus without mesh,
      and construction of a fundoplication anchored by sutures within the abdomen.
      RESULTS: Of the 55 patients, the operations of 49 were completed laparoscopically
      using the following reconstructions: Guarner (270-degree) fundoplication (30
      patients); Nissen fundoplication (10 patients); and gastropexy (9 patients). Five
      (9%) operations were converted to laparotomies. The average operating time was
      219 minutes; the average blood loss was less than 25 mL; resumption of an
      unrestricted diet, 27 hours; and mean hospital stay, 58 hours. Intraoperative
      technical complications occurred in five (9%) patients. One patient died during
      surgery from a sudden pulmonary embolus. Two (4%) patients required a second
      operation for recurrent paraesophageal hernias. CONCLUSIONS: Laparoscopic repair
      of paraesophageal hiatal hernias is safe and effective, but the operation is
      difficult and good results hinge on details of the operative technique and the
      surgeon's experience. In this series, the crus could always be closed securely
      without using mesh. We realized early that a fundoplication should be a routine
      step, because it corrects reflux and is the best method to secure the
      gastroesophageal junction in the abdomen.

PMID- 9544958
TI  - Gastric mucosal protection from enteral nutrients: role of motility.
AB  - BACKGROUND: Cold restraint stress increases the force of gastric contractions and
      produces gastric mucosal injury in rats. The aim of our study was to determine
      whether enteral glucose or hyperglycemia alone would alter the stress-induced
      gastric motility pattern and ameliorate the associated gastric mucosal injury.
      METHODS: Adult male rats underwent surgical placement of gastric catheters,
      jugular venous catheters, and gastric strain gauge transducers 5 days before cold
      restraint. Three groups of rats received different substances during the same
      cold restraint stress protocol. Group 1 received 0.9% NaCl, 2 mL/h infused both
      intravenously (i.v.) and intragastrically (i.g.); group 2 received 0.9% NaCl, 2
      mL/h i.g. plus 25% glucose, 2 mL/h i.v.; and group 3 received 0.9% NaCl, 2 mL/h
      i.v. plus 25% glucose i.g. Following baseline gastric motility measurements, all
      rats were restrained for 2 hours at 20 degrees C followed by 2 hours at 4 degrees
      C. RESULTS: Restraint even at room temperature increased the force of gastric
      contractions; the cold environment gradually prolonged gastric contractions.
      Enteral glucose blunted the effects of stress on gastric motility, increased
      gastric residual volume, decreased gastric acidity, and prevented gastric mucosal
      injury. Parenteral glucose had little effect on any gastric parameters.
      CONCLUSIONS: Enteral glucose prevents the abnormal gastric motility pattern that
      is necessary to produce the gastric mucosal injury associated with cold restraint
      stress, but hyperglycemia alone has little effect on the pathophysiology of cold
      restraint.

PMID- 9544959
TI  - Intraoperative abandonment of ileal pouch to anal anastomosis--the Mayo Clinic
      experience.
AB  - BACKGROUND: Completion of the ileal pouch to anal anastomosis (IPAA) is neither
      always possible nor advisable based on intraoperative findings. This study was
      undertaken to document the incidence of and reasons for intraoperative
      abandonment of IPAA in a series of over 1,700 attempts. STUDY DESIGN: A
      retrospective review of the Mayo Clinic surgical index from January 1981 through
      December 1995. Patients with the preoperative diagnosis of chronic ulcerative
      colitis or familial adenomatous polyposis for whom IPAA was planned but not
      completed are the subject of this report. Comparison is made to patients with a
      completed IPAA from the Mayo Clinic IPAA registry. RESULTS: During a 15-year
      period, 1,789 IPAA attempts were made. Intraoperative abandonment occurred in 74
      (4.1%). Patients in whom the operation was abandoned were older than patients in
      whom it was not (38 versus 33 years, p < 0.01), with age older than 40 years
      conferring a relative risk of 1.87 versus age younger than 40 (95% confidence
      interval, 1.19-2.94%). IPAA was abandoned for technical reasons in 32 (43%),
      intraoperative diagnosis of Crohn's disease in 27 (36%), colorectal cancer in 10
      (14%), mesenteric desmoid in 3 (4%), and miscellaneous reasons in 2 (3%)
      patients. Fifty-one (69%) patients underwent proctocolectomy and ileostomy and 23
      (31%) underwent sphincter preserving procedures. Of these, 2 underwent subsequent
      successful IPAA. CONCLUSIONS: Preoperative counseling for IPAA should include
      discussion of the risk of intraoperative abandonment (4.1%). Older patients are
      at increased risk. If the IPAA is abandoned for reversible reasons, preservation
      of the anal sphincter preserves the option of a subsequent IPAA.

PMID- 9544960
TI  - Three thousand one hundred seventy-five primary inguinal hernia repairs:
      advantages of ambulatory open mesh repair using local anesthesia.
AB  - BACKGROUND: Controversy exists over the relative advantages of open mesh repair
      compared with open stitching methods and the laparoscopic approach. STUDY DESIGN:
      Two thousand nine hundred six (2,906) consecutive unselected adult patients
      underwent 3,175 primary inguinal hernia repairs using polypropylene mesh, under
      local anesthesia on an ambulatory basis. The age range was 15-92 years. The study
      specifically investigated the postoperative course with regard to pain,
      complications, and time of return to work. RESULTS: There were no postoperative
      deaths and no cases of urinary retention. Two percent of patients developed a
      hematoma. The incidence of deep infection was 0.3%. No case of testicular atrophy
      occurred. Postoperatively 19% of patients used no analgesia at all; 60% used oral
      analgesics for up to 7 days. There was a gradual decrease in time of return to
      work over four successive 1-year periods. Manual workers returned to work in 15
      days (median) in the first year, reducing to 9 days in the fourth year. The
      overall median time of return to work across the whole group was 9 days. There
      were eight recurrences with an 18-month to 5-year followup. CONCLUSIONS: Open
      mesh repair under local anesthesia is an effective day case technique,
      particularly in the elderly and medically unfit. The economic benefits are
      enhanced by low morbidity, early return to normal activities and low recurrence
      rates.

PMID- 9544961
TI  - The past is prologue: surgeons then and now.

PMID- 9544963
TI  - Biology and treatment of peritonitis: the historic development of current
      concepts.

PMID- 9544962
TI  - Reflections on informed consent: 40 years after its birth.

PMID- 9544964
TI  - Knot properties of alternating sliding knots with different patterns in
      comparison to alternating and simple sliding knots.
AB  - This study attempts to compare the alternating sliding knots with different
      patterns with the alternating and simple sliding knots. Silk and nylon sutures of
      2-0 and 4-0 United States Pharmacopeia (USP) sizes were mechanically tested. The
      values of knot holding capacities (KHCs) varied depending on knot configuration,
      suture material, and size. The parallel alternating knot with different patterns
      showed a high KHC for silk suture of both sizes. For nylon, the alternating knots
      with different patterns were comparable to the simple sliding knots. When we
      compared silk with nylon in knots with different patterns we observed the
      following. For size 2-0 loops, the nonidentical knot of nylon was higher in KHC
      than that of silk, and the parallel knot of silk was higher in KHC than that of
      nylon. Loops of 4-0 showed higher KHCs for the parallel knot in nylon than in
      silk but similar values for both materials with the nonidentical knot. The
      parallel alternating knot with different patterns was the most efficient for
      nylon 4-0. The silk loops had good efficiencies for both sizes. The silk suture
      knots were all reliable. The nylon suture showed unreliability for the parallel
      and alternating nonidentical knots of both sizes and the alternating parallel
      knot in 2-0 suture. The results section discusses the physical structure and
      suture dimension. This study did not prove that the strength of the knot
      increases with complexity.

PMID- 9544965
TI  - Open technique during laparoscopic operations.

PMID- 9544966
TI  - The hernia repair debate.

PMID- 9544967
TI  - Aortic cannulation in organ donors with pathology of the infrarenal aorta.

PMID- 9544968
TI  - Aortic cannulation in organ donors with pathology of the infrarenal aorta.

PMID- 9544969
TI  - Combined effect of two different polymorphic sequences within the beta globin
      gene cluster on the level of HbF.
AB  - Beta thalassemia and Hb Lepore heterozygotes included in this study exhibit fetal
      hemoglobin levels varying from trace quantities to 14% (1.74 g/dl) of total
      hemoglobin in the adult. In this work, we have examined the correlation of DNA
      sequence polymorphisms with the observed HbF level. The analysis of polymorphic
      markers within the beta globin cluster in 39 individuals heterozygous for beta
      thalassemia or Hb Lepore confirms the previous findings for homozygous beta
      thalassemia: the presence of both an (AT)9 T5 sequence configuration at position 
      540 of the beta globin gene and a (C --> T) variation at -158 of the Ggamma
      globin gene is associated with elevated expression of HbF. However, at least one
      defective beta globin gene is required to reveal this association. The best
      evidence is from the study of individuals heterozygous for Hb Lepore with various
      levels of HbF. In these individuals it was possible to explore the effect of a
      single (AT)x Ty motif (the other being absent from the rearranged Lepore
      chromosome) on HbF expression. The presence of the (AT)9 T5 configuration
      increases HbF level from a median of 0.515 g/dl observed in (AT)7 T7 subjects, to
      1.39 g/dl. We confirm the existence of linkage disequilibrium between the (C -->
      T) variation at -158 of Ggamma gene and the (TG)13 configuration at the second
      intervening sequence (IVS-2) of Agamma gene and identify two new polymorphisms in
      this region: (TG)7 (CG)5 (TG)8 linked to haplotype V and (TG)8 (CG)5 (TG)10
      linked to haplotype II. This study suggests that two distinct regions of the beta
      cluster, whether in cis or in trans to each other, can interact to enhance HbF
      expression when a beta thalassemic determinant is present in heterozigosity.

PMID- 9544970
TI  - Aspirin increases the bleeding side effects in essential thrombocythemia
      independent of the cyclooxygenase pathway: role of the lipoxygenase pathway.
AB  - Acetylsalicylic acid (ASA) is currently recommended as an antithrombotic for
      patients with essential thrombocythemia (ET) who are at an increased risk of
      thrombotic events. However, ASA is also associated with an increased risk of
      bleeding in these patients as compared to the risk of bleeding in other patients
      treated with ASA. Recent data suggest that while ASA inhibits platelet
      thromboxane A2 (TxA2) synthesis in all individuals, ASA has little effect or
      inhibits the lipoxygenase pathway (i.e., 12-hydroxyeicosatetranoic acid or 12
      HETE synthesis) in some individuals, and enhances 12-HETE synthesis in others.
      These differential effects are associated with a pronounced prolongation of the
      bleeding time vs. no prolongation of the bleeding time, respectively, i.e., in
      ASA responders and ASA nonresponders, respectively. To determine if the increased
      risk of ASA-induced bleeding seen in ET patients is associated with an effect on
      12-HETE synthesis, we compared the relative effects of ASA on the bleeding time,
      platelet TxA2 and 12-HETE synthesis, and platelet aggregation and adhesion in ET
      patients and healthy volunteers. ASA (300 mg, taken orally) prolonged the
      bleeding time in 82% of the ET patients but only 27% of the healthy volunteers
      although platelet TxA2 synthesis and ADP- and collagen-induced aggregation were
      inhibited significantly in both groups. In contrast, platelet 12-HETE synthesis
      was unchanged and platelet adhesion was decreased in those patients and
      volunteers whose bleeding times were prolonged by ASA, whereas platelet 12-HETE
      synthesis was increased significantly and platelet adhesion was unaffected in
      those patients and volunteers whose bleeding times were not prolonged, and in
      some cases shortened by ASA. These results confirm previous data that demonstrate
      that ASA has different effects on platelet 12-HETE synthesis and platelet
      adhesion in different individuals, i.e., inhibitory or no effect in ASA
      responders (in whom ASA prolonged bleeding) vs. enhancing effects in ASA
      nonresponders (in whom ASA did not prolong bleeding). These results also indicate
      that there is a greater percentage of ASA responders in patients with ET than
      that seen in the general population, a difference that is associated with an
      effect of ASA on the lipoxygenase pathway. This may explain the increased
      bleeding side effects seen in the ET patient population.

PMID- 9544971
TI  - Detection of zeta-globin chains in the cord blood by ELISA (enzyme-linked
      immunosorbent assay): rapid screening for alpha-thalassemia 1 (Southeast Asian
      type).
AB  - Fetuses with homozygous alpha-thalassemia 1, in which the deletion of all four
      alpha-globin genes results in the absence of any alpha-globin chains, are
      severely anemic with clinical features of hydrops fetalis. Definitive diagnosis
      of alpha-thalassemia 1 carriers is difficult since there are few red cell
      abnormalities. Recently Chui et al. found that minute amounts of embryonic zeta
      globin chains are present in adult hemoglobin of the Southeast Asian type of
      alpha-thalassemia 1 carriers. In this study, we screened 521 cord bloods for
      alpha-thalassemia 1. Hemoglobin analysis, including quantitation of Hb Bart's,
      was performed using the automated HPLC, alpha-thalassemia short program (VARIANT,
      Bio-Rad, Hercules, CA). Of these, 200 cord blood samples in which Hb Bart's was
      demonstrated were tested for the presence of zeta-globin chains by ELISA using
      labeled anti-zeta monoclonal antibody. Zeta-globin ranged between 0.21 and 0.83%
      in 19 specimens carrying alpha-thalassemia 1 gene. In the remaining 90 out of 109
      specimens in which Hb Bart's was greater than 1.2%, zeta-globin was less than
      0.17%. DNA analysis revealed the presence of normal alpha-genotype and other
      types of alpha-thalassemia including alpha-thalassemia 2 and Hb Constant Spring.
      One false positive was found in which the zeta-globin was 0.25% by ELISA but in
      which PCR indicated an alpha-thalassemia 2 heterozygote. Ninety-one samples with
      Hb Bart's of less than 1.2% by HPLC are most likely normal with a zeta-globin
      range between 0 and 0.14%. This study also showed that the frequency of alpha
      thalassemia 1 in Bangkok is 3.65%.

PMID- 9544972
TI  - Decreased numbers of circulating B cells in myeloma patients with reduction after
      conventional chemotherapy.
AB  - Reports of high numbers of circulating monotypic B cells in patients with
      multiple myeloma (MM) have recently been published. These cells, which were
      identified by their expression of CD19, were reported to be resistant to
      conventional chemotherapy and to represent the source of relapse. We examined
      blood samples from 48 patients before and 53 patients after glucocorticoid
      containing chemotherapy by dual color flow cytometry. The absolute count of
      CD19+B cells in patients before treatment (212.6+/-24.8 x 10(6)/l) was decreased
      compared to normal controls (P = .038). In the post-treatment group, circulating
      B cells were highly significantly lower than in untreated patients (45.23+/-6.69
      x 10(6)/l. P < .001). This reduction was also seen in 26 patients, that were
      followed during chemotherapy. The cytoplasmic kappa/lambda ratio was within
      normal range before and after treatment with no difference according to the light
      chain isotype of the paraprotein. We conclude that circulating B cells are not
      increased in patients with MM, that the majority of these cells are polyclonal,
      and that conventional chemotherapy effectively reduces circulating B cells
      without leading to dominance of resistant monotypic cells.

PMID- 9544973
TI  - Increased von Willebrand factor binding to platelets in single episode and
      recurrent types of thrombotic thrombocytopenic purpura.
AB  - Extensive microvascular platelet aggregation is characteristic of thrombotic
      thrombocytopenic purpura (TTP). Previous studies have indicated that
      abnormalities of von Willebrand factor (vWf) are often present in TTP patient
      plasma. There has not been previously any direct evidence linking these
      abnormalities to the process of intravascular platelet aggregation in TTP. We
      used flow cytometry to analyze the binding of vWf to single platelets, and the
      presence of platelet aggregates, in the blood of 4 children with chronic
      relapsing (CR) TTP and 5 adults with single episode or recurrent TTP. vWf on the
      single platelets of CRTTP patients at all time points studied was significantly
      increased compared to controls, and was increased further as platelet counts
      decreased to levels below 40,000/microl. The single episode and recurrent adult
      TTP patients had platelet aggregates in the blood, as well as increased vWf on
      single platelets, before therapy commenced and thereafter until recovery was in
      process. In the one unresponsive single episode TTP patient, vWf on single
      platelets remained elevated, and platelet aggregates persisted, until her death.
      The platelet alpha-granular protein, P-selectin, was not increased on the single
      platelets of most TTP blood samples, suggesting that it is vWf from plasma
      (rather than from alpha-granules) that attaches to platelet surfaces in
      association with platelet aggregation. These results suggest that vWf-platelet
      interactions are involved in the platelet clumping process that characterizes
      TTP.

PMID- 9544974
TI  - Recombinant human granulocyte colony-stimulating factor (G-CSF) combined
      conditioning regimen for allogeneic bone marrow transplantation (BMT) in standard
      risk myeloid leukemia.
AB  - We previously suggested that using a combined conditioning regimen including rhG
      CSF with allogeneic BMT in refractory AML and CML in blast crisis might reduce
      the rate of relapse and improve disease-free survival, without any major side
      effects. In this study, we used the same protocol for 10 AML patients in complete
      remission (CR) and 6 CML patients in the chronic phase (CP). We compared disease
      free survival as well as toxic side effects of the regimen with 6 AML patients in
      CR and 6 CML patients in CP treated with chemoradiotherapy without G-CSF. The
      conditioning regimen consisted of TBI and high-dose AraC. RhG-CSF was infused
      continuously at a dose of 5 microg/kg/day, starting 24 hr before the initial dose
      of total body irradiation (TBI) until the end of AraC therapy. In all 28 cases,
      there were no early stage deaths due to regimen-related toxicity (RRT). None of
      the 10 AML cases treated with the G-CSF combined regime relapsed. In 6 AML cases
      treated conventionally without G-CSF, one patient died of infection and another
      relapsed. There were no relapses in either CML group. In the combined G-CSF
      group, one patient died of interstitial pneumonitis 48 days after BMT, while the
      rest of the CML cases are still alive. There were no relapses with rhG-CSF and no
      serious adverse effects in terms of RRT, acute graft vs. host disease (GVHD), or
      leukocyte recovery.

PMID- 9544975
TI  - Plasma fibronectin during myocardial ischemia-reperfusion: effects of magnesium,
      diltiazem, and a novel Mac-1 inhibitor.
AB  - The important role of fibronectin (Fn) has been recognized in patients with
      ischemic heart disease. However, serial changes of Fn during both brief and
      prolonged ischemia-reperfusion are poorly known. Plasma Fn was measured during
      acute myocardial infarction (AMI) and myocardial stunning (MS), and in the
      absence of myocardial injury. The effects of magnesium (Mg), diltiazem, and a Mac
      1 inhibitor on the level of Fn were elucidated. Forty-nine swine underwent
      prolonged (50 min) or brief (8 min) coronary artery occlusion followed by
      reperfusion, while six control animals were free of ischemia. During the AMI
      experiments, plasma Fn underwent a significant progressive increase. Mg or
      diltiazem similarly affects the plasma Fn, reducing its release during the entire
      reperfusion period, and did not influence the plasma Fn in the absence of
      myocardial injury. Contrarily, Mac-1 inhibition resulted in the Fn elevation in
      controls, and during the occlusion phase, with no significant effect during
      reperfusion. There were no changes in the plasma Fn during MS, while inhibition
      of Mac-1 was associated with the significant increase of Fn during ischemia
      reperfusion. Ability of Mg, diltiazem, and leumedins to modulate plasma Fn level
      may have direct clinical implications for the use of these agents in patients
      with coronary artery disease.

PMID- 9544976
TI  - Rapid detection of anticardiolipin antibodies.
AB  - A rapid screening method for the detection of antiphospholipid antibodies is
      described. Dense, red dyed polystyrene beads coated with cardiolipin were
      incubated with test sera for a short period of time, then added to a microtube
      containing anti-human IgG in a gel provided within a pre-cast card (DiaMed ID
      Microtyping System). The card was centrifuged at 150g for 5 min and then examined
      for movement of the beads through the gel. Beads without bound antibody travelled
      through the gel and formed a pellet on the bottom of the tube. Anti-human IgG
      within the gel matrix impeded cardiolipin-coated beads when antiphospholipid
      antibodies bound to the beads. Positivity was indicated by the formation of a
      layer of beads on the top of the gel matrix. Prospective analysis of 103 samples
      for the presence of antiphospholipid antibodies by flow cytometry and the gel
      card technique showed good correlation between the two methods. All samples found
      to be positive by flow cytometry (23 of 103) were identified as positive by the
      gel-card technique. Two samples were identified as positive by the gel-card
      method but negative by flow cytometry. The technique is simple to perform and
      should prove useful as a rapid screening method for the detection of
      antiphospholipid antibodies.

PMID- 9544977
TI  - Chronic myeloid leukemia with minor-bcr breakpoint developed hybrid type of blast
      crisis.
AB  - Although a breakpoint in the minor breakpoint cluster region (m-bcr) of the BCR
      gene is observed in about two-thirds of patients with Philadelphia chromosome
      positive acute lymphoblastic leukemia, this type of genomic rearrangement occurs
      very rarely in chronic myeloid leukemia (CML). We describe here the eighth case
      of m-bcr CML, and delineate unique clinical characteristics found in common to
      the 7 cases reported previously. Monocytosis with a low neutrophil/monocyte ratio
      resembling chronic myelomonocytic leukemia was the most striking feature of m-bcr
      CML. Splenomegaly and basophilia were not conspicuous in chronic phase. A high
      percentage of immature granulocytes and low neutrophil alkaline phosphatase score
      were the findings in common with classical CML. Lymphoid and myeloid blast
      changes have been observed at and shortly after presentation so far. We found a
      hybrid type of blast crisis in the course of m-bcr CML.Thus, m-bcr CML may be a
      definite subtype of CML, exhibiting distinct clinical characteristics. The
      presence of fusion product of m-bcr mRNA in an earlier myeloid cell may involve
      monocytic lineage in addition to myeloproliferative defects.

PMID- 9544978
TI  - Transfusion management of an IgA deficient patient with anti-IgA and incidental
      correction of IgA deficiency after allogeneic bone marrow transplantation.
AB  - A patient with multiple myeloma was noted to have an IgA deficiency during
      investigation of a possible transfusion reaction due to IgA deficiency and anti
      IgA. Because of the patient's age, otherwise good health, and early stage of
      disease, he was enrolled in a research treatment protocol that involved an
      allogeneic bone marrow transplant (BMT). The BMT successfully put the patient in
      complete remission from his multiple myeloma and corrected his IgA deficiency.
      Class-specific IgG anti-IgA antibody that had been identified prior to BMT was no
      longer detectable in his plasma. Anaphylactic transfusion reactions were
      successfully avoided by using a combination of IgA-deficient and washed blood
      components including the marrow graft, and IgA-reduced intravenous
      immunoglobulin.

PMID- 9544980
TI  - Immunologic thrombocytopenic purpura as presenting symptom of hepatitis C
      infection.
AB  - We report on 3 female patients with immunologic thrombocytopenic purpura (ITP)
      for whom diagnostic procedures evidenced a chronic Hepatitis C virus (HCV)
      infection. In 2 cases, a transfusion performed more than 10 years ago represented
      the probable way of contamination. One patient received a course of steroids,
      which normalized the platelet counts. Another one has been treated with repeated
      IV immunoglobulins, which induced partial responses of variable duration. HCV is
      responsible for many autoimmune manifestations and a search for this virus seems
      warranted for exploring patients with ITP.

PMID- 9544979
TI  - T-cell lymphoma associated with natural killer-like T-cell reaction.
AB  - We report a case of T-cell lymphoma showing in the peripheral blood (PB)
      exclusively T-lymphocytes with suppresser T-cell preponderance and a high
      percentage of natural killer (NK) marker positive cells by flow cytometry. A T
      cell receptor (TCR) gene analysis of the PB leukocytes demonstrated
      rearrangements of TCRalpha, TCRbeta, and TCRgamma genes. Therefore, the phenotype
      and genotype appeared to be consistent with an NK-like T-cell leukemia/lymphoma.
      However, when the PB lymphocytes were separated by size, it was found that 80% of
      NK marker positive cells were in the smaller cell population, while the
      neoplastic cells were in the large cell gate. A diagnosis of T-cell lymphoma with
      reactive NK-like T-cells was finally confirmed by demonstrating the presence of
      both large atypical lymphoid cells and large granular lymphocytes (LGL) on PB
      smears. Although immunoperoxidase stain of bone marrow and colon showed positive
      T-cell markers in the tumor cell population, cytoplasmic granules could not be
      identified in tissue sections and, thus, a distinction between T-cell lymphoma
      and NK-like T-cell lymphoma could not be made by light microscopy until NK
      markers were studied. CD57 was demonstrated immunohistochemically in small
      lymphocytes but not in the large tumor cells in the colon. Electron microscopy,
      however, demonstrated LGL reaction to the lymphoma cells in the colonic biopsy.
      NK-like T-cell lymphoma usually carries a poorer prognosis than peripheral T-cell
      lymphoma, thus the distinction of these neoplasms is important. This study
      emphasizes that T-cell lymphoma may cause an LGL reaction or proliferation. If
      the lymphoma cells were of the same size as LGL, flow cytometric studies may have
      misled the diagnosis to NK-like T-cell-lymphoma.

PMID- 9544981
TI  - Oxidized LDL damages endothelial cell monolayer and promotes thrombocyte
      adhesion.
AB  - The influence of oxidized low density lipoprotein (LDL) on a human endothelial
      cell monolayer was examined. The resulting contraction of the oxidized LDL
      damaged endothelial cells lets intercellular spaces become enlarged and therefore
      visible via light microscopy. Electron microscopy reveals that the structural
      damage facilitates thrombocyte adhesion and formation of microthrombi. Oxidized
      LDL appears to play a pivotal role in initiating and deteriorating thromboembolic
      complications.

PMID- 9544982
TI  - Low risk of venous thrombosis in two families with combined type I plasminogen
      deficiency and factor V R506Q mutation.
AB  - Two families with type I plasminogen deficiency and APC resistance are reported.
      The proposita of family A suffered from ischemic stroke when taking estrogen
      progesterone-containing oral contraceptive. Several hemostatic challenges in the
      past (ovariectomy, appendectomy, and two pregnancies) were without thrombosis.
      Plasminogen activity and antigen (60 and 58%, normal range 72-136 and 69-135%,
      respectively) were reduced, and an increased APC resistance (APC-SR= 1.55; normal
      range 1.8-3.00) associated with G --> A change at 1,691 nucleotide position in
      exon 10 of FV gene (FV Leiden) was observed. The asymptomatic son had isolated
      plasminogen deficiency (activity 57% and antigen 60%) whereas the asymptomatic
      daughter had isolated APC resistance (APC-SR = 1.61) and FV Leiden mutation. The
      proposita of family B, referred for superficial thrombophlebitis, had low
      plasminogen levels (activity 55% and antigen 53%) and APC resistance (APC-SR =
      1.5) whereas the asymptomatic mother and the brother had isolated APC resistance
      (APC-SR = 1.62 and 1.8, respectively) and the asymptomatic father isolated
      plasminogen deficiency (activity 61% and antigen 62%). These data suggest that
      the combination of plasminogen deficiency and APC resistance probably does not
      significantly increase the risk of venous thrombosis. However, larger experience
      with additional cases is needed to definitely assess the magnitude of thrombotic
      risk in these families.

PMID- 9544983
TI  - Oct-1 binds promoter elements required for transcription of the GnRH gene.
AB  - The GnRH gene is exclusively expressed in a discrete population of neurons in the
      hypothalamus. The promoter-proximal 173 bp of the rat GnRH gene are highly
      conserved through evolution and are bound by multiple nuclear proteins found in
      the neuronal cell line, GT1-7, a model for the GnRH-expressing hypothalamic
      neuron. To explore the protein-DNA interactions that occur within this promoter
      and the role of these interactions in targeting GnRH gene expression, we have
      mutagenized individual binding sites in this region. Deoxyribonuclease I
      protection experiments reveal that footprint 2, a 51-bp sequence that confers a
      20-fold induction of the GnRH gene, is comprised of at least three independent
      protein-binding sites. Transfections of the GnRH promoter-reporter plasmid
      containing a series of block mutations of footprint 2 into GT1-7 neurons indicate
      that each of the three putative component sites contributes to transcriptional
      activity. Mutations in footprint 4 also decrease GnRH gene expression. Footprint
      4 and the promoter-proximal site in footprint 2 contain octamer-like motifs, an
      element that is also present in the neuron-specific enhancer of the rat GnRH gene
      located approximately 1.6 kb upstream of the promoter. Previous studies in our
      laboratory have demonstrated that two enhancer octamer sites are bound by the POU
      homeodomain transcription factor Oct-1 in GT1-7 cells. We now show that Oct-1
      binds the octamer motifs within footprints 2 and 4. Thus, Oct-1 plays a critical
      role in the regulation of GnRH transcription, binding functional elements in both
      the distal enhancer and the promoter-proximal conserved region.

PMID- 9544984
TI  - Further characterization of the glucocorticoid response unit in the
      phosphoenolpyruvate carboxykinase gene. The role of the glucocorticoid receptor
      binding sites.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step of
      gluconeogenesis. The activity of this enzyme is controlled by several hormones,
      including glucocorticoids, glucagon, retinoic acid, and insulin, that principally
      affect the rate of transcription of the PEPCK gene. Glucocorticoids induce PEPCK
      gene transcription through a complex glucocorticoid response unit that consists
      of, from 5' to 3', accessory factor elements AF1 and AF2; two noncanonical
      glucocorticoid receptor-binding sites, GR1 and GR2; a third accessory factor
      element, AF3; and a cAMP-response element, CRE. A complete glucocorticoid
      response is dependent on the presence of both GR-binding sites, all three
      accessory elements, and the CRE. In this study we assess the relative roles of
      GR1 and GR2 in the context of the glucocorticoid response unit and use a
      combination of binding and function assays to compare GR1 and GR2 to
      glucocorticoid response elements (GREs) that conform closely to the consensus
      sequence. The relative binding affinity of GR follows the order: consensus GRE >>
      GR1 > GR2. Mutations that disrupt the binding of GR to GR1 result in a major
      reduction of the glucocorticoid response, whereas similar mutations of GR2 have a
      much smaller effect. Unlike the simple consensus GRE, neither GR1 nor GR2 mediate
      a glucocorticoid response through a heterologous promoter. The accessory elements
      appear to have different functional roles. AF2 is still needed for a maximal
      glucocorticoid response when GR1 is converted to a high-affinity GR-binding
      element, but AF1 and AF3 are not required.

PMID- 9544985
TI  - Differential regulation and transcriptional control of immediate early gene
      expression in forskolin-treated WEHI7.2 thymoma cells.
AB  - Agents that increase intracellular cAMP are frequently growth inhibitory for
      lymphocytes and induce apoptosis in cortical thymocytes by regulating gene
      expression. In the present study, immediate early gene expression was examined in
      WEHI7.2 thymoma cells undergoing cAMP-mediated apoptosis. Temporal differences in
      c-fos, junB, and inducible cAMP early repressor (ICER) steady-state mRNA levels
      were observed after forskolin exposure. Maximal induction of c-fos and junB
      occurred within 1 h, returning to basal levels by 3.5 h. In contrast, a 1.5-h
      time lag was observed before ICER transcript levels increased, reaching maximal
      levels after 3.5 h. This rise in expression, correlating with the decrease in c
      fos and junB levels, preceded apoptotic DNA fragmentation by 1.5 h. Transient
      expression of ICER promoter constructs demonstrated that cAMP responsiveness
      occurred through cAMP-autoregulatory response element (CARE)3/4, two of the four
      proposed response elements in the ICER promoter. In contrast to the cAMP
      responsive cell line JEG-3, CARE1/2 was not functional for cAMP-activated
      transcription in WEHI7.2 cells. An observed differential binding pattern of WEHI
      and JEG nuclear extracts to these elements may account for the cell-specific
      differences in expression patterns. To determine the role of endogenous ICER in
      regulating gene expression, cells were treated with two sequential doses of
      forskolin after which ICER and c-fos mRNA levels were measured. The high levels
      of cAMP-induced ICER expression dramatically reduced a second induction of c-fos.
      These data suggest that ICER expression may function as an antioncogene to
      attenuate the expression of certain protooncogenes, thereby preventing
      transformation and oncogenesis due to continuous overexpression. Moreover,
      inhibition of growth-stimulatory genes may be required for the activation of the
      cell death machinery in specific cells.

PMID- 9544986
TI  - Cell-specific inhibition of retinoic acid receptor-alpha silencing by the AF2/tau
      c activation domain can be overcome by the corepressor SMRT, but not by N-CoR.
AB  - The human retinoic acid receptor alpha (hRAR alpha) exhibits cell-specific
      transcriptional activity. Previously, it was shown that in the absence of hormone
      the wild-type receptor is a transcriptional silencer in L cells, whereas it lacks
      silencing function and is a weak activator in CV1 cells. Addition of hormone
      leads to a further increase in transactivation in CV1 cells. Thus, the retinoic
      acid response mediated by RAR alpha is weak in these cells. It was shown that the
      CV1-specific effect is due to the receptor C terminus. We show, that the failure
      of silencing by RAR is not due to a general lack of corepressors in CV1 cells,
      since the silencing domain of RAR is functionally active and exhibits active
      repression in these cells. Furthermore, we show that the conserved AF2/tau c
      activation function of RAR is responsible for the cell-specific inhibition of
      silencing. Thereby, the CV1 cell specificity was abolished by replacing AF2/tau c
      of RAR with the corresponding sequence of the thyroid hormone receptor. Thus, we
      find a new role of the C-terminal conserved activation function AF2/tau c in
      that, specifically, the RAR AF2/tau c-sequence is able to prevent silencing of
      RAR in a cell-specific manner. In addition, we show that the inhibitory effect of
      AF2/tau c in CV1 cells can be overcome by expression of the corepressor SMRT
      (silencing mediator of retinoic acid and thyroid hormone receptor), but not by
      that of N-CoR (nuclear receptor corepressor). The expression of these two
      corepressors, however, had no measurable effect on RAR-mediated silencing in L
      cells. Thus, the expression of a corepressor can lead to a dramatic increase of
      hormonal response in a cell-specific manner.

PMID- 9544987
TI  - A nuclear receptor corepressor modulates transcriptional activity of antagonist
      occupied steroid hormone receptor.
AB  - Synthetic steroid hormone antagonists are clinically important compounds that
      regulate physiological responses to steroid hormones. The antagonists bind to the
      hormone receptors, which are ligand-inducible transcription factors, and modulate
      their gene-regulatory activities. In most instances, a steroid receptor, such as
      progesterone receptor (PR) or estrogen receptor (ER), is transcriptionally
      inactive when complexed with an antagonist and competitively inhibits
      transactivation of a target steroid-responsive gene by the cognate hormone
      occupied receptor. In certain cellular and promoter contexts, however, antagonist
      occupied PR or ER acquires paradoxical agonist-like activity. The cellular
      mechanisms that determine the switch from the negative to the positive mode of
      transcriptional regulation by an antagonist-bound steroid receptor are unknown.
      We now provide strong evidence supporting the existence of a cellular inhibitory
      cofactor that interacts with the B form of human PR (PR-B) complexed with the
      antiprogestin RU486 to maintain it in a transcriptionally inactive state. In the
      presence of unliganded thyroid hormone receptor (TR) or ER complexed with the
      antiestrogen 4-hydroxytamoxifen, which presumably sequesters a limiting pool of
      the inhibitory cofactor, RU486-PR-B functions as a transcriptional activator of a
      progesterone-responsive gene even in the absence of hormone agonist. In contrast,
      hormone-occupied TR or ER fails to induce transactivation by RU486-PR-B. Recent
      studies revealed that a transcriptional corepressor, NCoR (nuclear receptor
      corepressor), interacts with unliganded TR but not with liganded TR.
      Interestingly, coexpression of NCoR efficiently suppresses the partial agonistic
      activity of antagonist-occupied PR-B but fails to affect transactivation by
      agonist-bound PR-B. We further demonstrate that RU486-PR-B interacts physically
      with NCoR in vitro. These novel observations suggest that the inhibitory cofactor
      that associates with RU486-PR-B and represses its transcriptional activity is
      either identical or structurally related to the corepressor NCoR. We propose that
      cellular mechanisms that determine the switch from the antagonistic to the
      agonistic activity of RU486-PR-B involve removal of the corepressor from the
      antagonist-bound receptor so that it can effect partial but significant gene
      activation.

PMID- 9544988
TI  - Differential use of transcription activation function 2 domain of the vitamin D
      receptor by 1,25-dihydroxyvitamin D3 and its A ring-modified analogs.
AB  - Analogs of 1,25-dihydroxyvitamin D3 (1,25D3) can be used to elucidate details of
      vitamin D receptor (VDR) activation. The A ring-modified analog, (TN-2) has 15
      fold less affinity for VDR, but its transcriptional activity is diminished 1000
      fold. Likewise, the ability of TN-2 to induce a protease-resistant conformation
      in VDR is 1/1000 that of 1,25D3. The stability of the VDR-TN-2 complexes is also
      significantly lower than VDR-1,25D3 complexes. Mapping the VDR-binding site of TN
      2 showed that it had a significantly greater requirement for transcription
      activation function 2 (AF-2) residues than 1,25D3 did. These results suggest that
      the increased requirement for AF-2 residues that was induced by the A ring
      modifications is associated with diminished receptor activation. To determine
      whether restoring the potency of TN-2 by additional structural modifications
      would change the requirements for AF-2 residues, we synthesized hybrid analogs
      with 1beta-hydroxymethyl-3-epi groups and with dimethyl groups at positions 26
      and 27 of the side chain, without or with a double bond between CD ring positions
      16 and 17. We found that the side chain modification enhanced transcriptional
      activity 150-fold, increased the ability of the receptor to form a protease
      resistant conformation 100-fold, and stabilized the VDR-analog complexes. The
      addition of the 16-ene group further reduced the analog's dissociation rate and
      increased its potency in the protease assays. These functional changes in the
      hybrid analogs were associated with a significant reduction in interaction with
      AF-2 residues. We conclude that there is an inverse relationship between analogs'
      potencies and their interaction with AF-2 residues of VDR.

PMID- 9544989
TI  - Shc phosphotyrosine-binding domain dominantly interacts with epidermal growth
      factor receptors and mediates Ras activation in intact cells.
AB  - The adaptor protein Shc contains a phosphotyrosine binding (PTB) domain and a Src
      homology 2 (SH2) domain, both of which are known to interact with phosphorylated
      tyrosines. We have shown previously that tyrosine 1148 of the activated epidermal
      growth factor (EGF) receptor is a major binding site for Shc while tyrosine 1173
      is a secondary binding site in intact cells. In the present study, we
      investigated the interaction between the PTB and SH2 domains of Shc and the
      activated human EGF receptor. Mutant 52-kDa Shc with an arginine-to-lysine
      substitution at residue 175 in the PTB domain (Shc R175K) or 397 in the SH2
      domain (Shc R397K) was coexpressed in Chinese hamster ovary cells overexpressing
      the wild-type or mutant EGF receptors that retained only one of the
      autophosphorylation sites at tyrosine 1148 (QM1148) or 1173 (QM1173). Shc R397K
      was coprecipitated with the QM1148 and QM1173 receptors, was tyrosine
      phosphorylated, and associated with Grb2 and Sos. In contrast, coprecipitation of
      Shc R175K with the mutant receptors was barely detectable. In cells expressing
      the QM1173 receptor, Shc R175K was tyrosine-phosphorylated and associated with
      Grb2, while association of Sos was barely detectable. In cells expressing the
      QM1148 receptor, tyrosine phosphorylation of Shc R175K was markedly reduced. When
      both Shc R175K and 46-kDa Shc R397K were coexpressed with the mutant receptors,
      p46 Shc R397K was dominantly tyrosine-phosphorylated. In cells expressing the
      wild-type receptor, Shc R397K, but not Shc R175K, translocated to the membrane in
      an EGF-dependent manner. In addition, Ras activity stimulated by the
      immunoprecipitates of Shc R397K was significantly higher than that by the
      immunoprecipitates of Shc R175K. The present results indicate that tyrosine 1148
      of the activated EGF receptor mainly interacts with the Shc PTB domain in intact
      cells. Tyrosine 1173 interacts with both the PTB and SH2 domains, although the
      interaction with the PTB domain is dominant. In addition, Shc bound to the
      activated EGF receptor via the PTB domain dominantly interacts with Grb2-Sos
      complex and plays a major role in the Ras-signaling pathway.

PMID- 9544990
TI  - N-glycosylation of the prolactin receptor is not required for activation of gene
      transcription but is crucial for its cell surface targeting.
AB  - The functional importance of the three oligosaccharide chains linked to Asn35,
      Asn80 and Asn108, of the long form of the PRL receptor (PRLR) was investigated by
      individual or multiple substitutions of asparagyl residues using site-directed
      mutagenesis and transient transfection of these mutated forms of PRLR in monkey
      kidney cells, Chinese hamster ovary, and human 293 fibroblast cells that exhibit
      different levels of protein expression. Scatchard analysis performed on monkey
      kidney cells revealed that the mutants possess the same affinity for PRL as
      compared with wild-type PRLR. A strong reduction (90%) of the aglycosylated PRLR
      expression at the cell surface of monkey kidney or human 293 cells was observed.
      Immunohistochemistry experiments using an anti-PRLR monoclonal antibody showed an
      accumulation of the deglycosylated receptor in the Golgi area of transfected
      monkey kidney cells. Upon PRL stimulation, the aglycosylated PRLR associated with
      Janus kinase 2 was phosphorylated and was able to activate a beta-casein gene
      promoter in transfected 293 fibroblast cells. The active form of the PRLR was
      thus acquired independently of glycosylation. By contrast, no functional activity
      was detectable in transfected Chinese hamster ovary cells that expressed low
      levels of PRLR. These studies demonstrate that the glycosylation on the asparagyl
      residues of the extracellular domain of the PRLR is crucial for its cell surface
      localization and may affect signal transduction, depending on the cell line.

PMID- 9544991
TI  - Dominant negative variants of the SHP-2 tyrosine phosphatase inhibit prolactin
      activation of Jak2 (janus kinase 2) and induction of Stat5 (signal transducer and
      activator of transcription 5)-dependent transcription.
AB  - PRL plays a central role in the regulation of milk protein gene expression in
      mammary epithelial cells and in the growth and differentiation of lymphocytes. It
      confers its activity through binding to a specific transmembrane, class I
      hematopoietic receptor. Ligand binding leads to receptor dimerization and
      activation of the tyrosine kinase Jak (janus kinase) 2, associated with the
      membrane-proximal, intracellular domain of the receptor. Jak2 phosphorylates and
      activates Stat5, a member of the Stat (signal transducers and activators of
      transcription) family. PRL receptor also activates SHP-2, a cytosolic tyrosine
      phosphatase. We investigated the connection between these two signaling events
      and derived a dominant negative mutant of SHP-2 comprising the two SH2 domains
      [SHP-2(SH2)2]. An analogous variant of the SHP-1 phosphatase [SHP-1(SH2)2] was
      used as a control. The dominant negative mutant of SHP-2 was found to inhibit the
      induction of tyrosine phosphorylation and DNA-binding activity of m-Stat5a, m
      Stat5b, and the carboxyl-terminal deletion variant m-Stat5adelta749, as well as
      the transactivation potential of m-Stat5a and m-Stat5b. The dominant negative
      mutant SHP-1(SH2)2 had no effect. The kinase activity of Jak2 is also dependent
      on a functional SHP-2 phosphatase. We propose that SHP-2 relieves an inhibitory
      tyrosine phosphorylation event in Jak2 required for Jak2 activity, Stat5
      phosphorylation, and transcriptional induction.

PMID- 9544993
TI  - The agonist-induced phosphorylation of the rat follitropin receptor maps to the
      first and third intracellular loops.
AB  - Previous results from this laboratory have shown that the rat FSH receptor
      (rFSHR) becomes phosphorylated on S/T residues upon stimulation of transfected
      cells with human (h)FSH and that a truncation of the C-terminal tail that removes
      12 of the 25 intracellular S/T residues does not affect phosphorylation. Based on
      the results of phosphopeptide-mapping experiments we analyzed three new mutants.
      rFSHR-1L and rFSHR-3L were constructed by mutating the S/T residues in the first
      intracellular loop or the third intracellular loop, respectively. rFSHR-(3L+CT)
      was constructed by mutating all the S/T residues in the third loop as well as
      S624, the only C-terminal tail residue that was not previously eliminated as a
      potential phosphorylation site. All mutants were biologically active. The agonist
      induced phosphorylation of rFSHR-3L and rFSHR-(3L+CT) were partially reduced,
      while that of rFSHR-1L was almost completely lost. The agonist-induced uncoupling
      of rFSHR-1L and rFSHR-3L are retarded to about the same extent, while the agonist
      induced internalization is retarded only in rFSHR-1L. Four major conclusions can
      be made from the present studies: 1) the phosphorylated rFSHR is a common
      molecular intermediate in agonist-induced uncoupling and internalization; 2)
      agonist-induced phosphorylation of the rFSHR maps to the first and third
      intracellular loops; 3) the phosphorylation of the third intracellular loop
      facilitates agonist-induced uncoupling but is not necessary for agonist-induced
      internalization; 4) agonist-induced internalization is facilitated by
      phosphorylation but it is not known if only the first loop, only the third loop,
      or both the first and third loops need to be phosphorylated for this response.

PMID- 9544992
TI  - Extinction of insulin-like growth factor-I mitogenic signaling by antiestrogen
      stimulated Fas-associated protein tyrosine phosphatase-1 in human breast cancer
      cells.
AB  - Steroidal (ICI 182, 780) and nonsteroidal hydroxytamoxifen (OH-Tam) antiestrogens
      inhibit growth factor-mitogenic activity in MCF 7 estrogen receptor-positive
      human breast cancer cells. Cell inhibition is correlated with an increase in
      membrane protein tyrosine phosphatase (PTP) activity, and the addition of
      orthovanadate prevents OH-Tam inhibition. After RT-PCR cloning of PTPs expressed
      in MCF 7 cells with primers to their catalytic domains, we have shown, by
      differential screening, that the expression of two enzymes, leukocyte common
      antigen-related PTP (LAR) and Fas-associated PTP-1 (FAP-1), was modulated by
      antiestrogens. By comparative RT-PCR, in situ hybridization, and Northern blot,
      LAR and FAP-1 mRNAs accumulation was found to be dose- and time-dependently
      increased by antiestrogens. To further demonstrate that PTPs were key mediators
      of antiestrogen-inhibitory action on the growth factor pathway, a panel of stable
      FAP-1 transfectants expressing low to high levels of antisense mRNAs was
      established. In these clones, the level of antisense RNA expression was
      correlated with a reduction in basal levels and a complete inhibition of
      antiestrogen-stimulated values of PTP activity. When FAP-1 expression was
      abolished, OH-Tam was no longer able to block insulin-like growth factor I
      mitogenic activity even though it remained strongly antiestrogenic. However, ICI
      182,780 was still inhibitory, indicating that its effect was not exclusively
      mediated by PTP. Our data first demonstrate that a specifically regulated
      phosphatase (FAP-1) is implicated in the triggering of negative proliferation
      signals in breast cancer cells.

PMID- 9544994
TI  - A ligand-mimetic model for constitutive activation of the melanocortin-1
      receptor.
AB  - Dark coat color in the mouse and fox results from constitutively activated
      melanocortin-1 receptors. Receptor mutations in the mouse (E92K, L98P), cow
      (L99P), fox (C125R), and sheep (D119N) cluster near the membrane/extracellular
      junctions of the second and third transmembrane domains, an acidic domain that is
      the likely site of electrostatic interaction with an arginine residue in the
      ligand, alpha-MSH. For transmembrane residues E92, D119, and C125, conversion to
      a basic residue is required for constitutive activation. Unlike constitutively
      activating mutations in many G protein-coupled receptors that increase agonist
      efficacy and affinity, these MC1-R mutations have the opposite effect. Therefore,
      these mutations do not activate the receptor by directly disrupting
      intramolecular constraints on formation of the active high-affinity state, R*,
      but do so indirectly by mimicking ligand binding.

PMID- 9544995
TI  - Epithelial tight junction structure in the jejunum of children with acute and
      treated celiac sprue.
AB  - Tight junction morphology was analyzed in freeze fracture electron micrographs
      from biopsies at two locations along the surface-crypt axis in the jejunum of
      children with treated and untreated sprue and in control subjects. In control
      jejunum, strand number, meshwork depth, and total depth of the tight junction
      decreased from surface to crypt, consistent with the concept of the crypt being
      more permeable than the surface epithelium. In acute sprue, strand number was
      reduced in all regions along the surface-crypt axis, from 5.5+/-0.2 to 3.4+/-0.3
      (surface) and from 4.7+/-0.2 to 3.6+/-0.1 (crypt). Meshwork depth was also
      reduced at all regions along the surface-crypt axis. Strand discontinuities were
      more frequent in acute sprue. Aberrant strands appeared below the main meshwork
      of crypt tight junctions in acute sprue. In asymptomatic children treated with
      the gluten-free diet, jejunal tight junctional structure only partially
      recovered. Strand number was restored to normal at the surface, but was still
      decreased in the crypts, from 4.7+/-0.2 to 3.9+/-0.3. We conclude that the
      epithelial barrier function of the small intestine is seriously disturbed by
      structural modifications of the tight junction in acute symptomatic celiac
      disease, thereby accounting for increased ionic permeability noted in a parallel
      study on identical specimens. This epithelial barrier defect may contribute to
      diarrhea in celiac disease by a "leak flux mechanism." In children with sprue
      treated with a gluten-free diet, barrier dysfunction was only partly recovered,
      suggesting a level of "minimal damage."

PMID- 9544996
TI  - Arginine-metabolizing enzymes in the developing rat small intestine.
AB  - Before weaning, arginine biosynthesis from citrulline most likely takes place in
      the small intestine rather than in the kidney. We studied the expression of
      ornithine cycle enzymes in the rat small intestine during perinatal development.
      The spatiotemporal patterns of expression of ornithine aminotransferase,
      carbamoylphosphate synthetase, ornithine transcarbamoylase, argininosuccinate
      synthetase, argininosuccinate lyase, and arginase mRNAs were studied by Northern
      blot analysis and in situ hybridization. In addition, the expression of
      carbamoylphosphate synthetase and argininosuccinate synthetase protein was
      studied by immunohistochemistry. Before birth, the developmentally more mature
      proximal loops of the intestine expressed the mRNAs at higher concentrations than
      the more distal loops. After birth, this difference was no longer obvious. The
      mRNAs of argininosuccinate synthetase and argininosuccinate lyase, the enzymes
      that metabolize citrulline to arginine, were detectable only in the upper part of
      the villi, whereas the other mRNAs were concentrated in the crypts. The
      distribution of argininosuccinate synthetase protein corresponded with that of
      the mRNA, whereas carbamoylphosphate synthetase protein was present in all
      enterocytes of the crypts and villi. Hepatic arginase mRNA could not be detected
      in the enterocytes. The spatial distribution of the respective mRNAs and proteins
      along the villus axis of the suckling small intestine indicates that the basal
      enterocytes synthesize citrulline, whereas the enterocytes in the upper half of
      the villus synthesize arginine.

PMID- 9544997
TI  - Metabolic and endocrine responses to cold exposure in chronically incubated
      extrauterine goat fetuses.
AB  - To investigate developmental aspects of metabolic and endocrine responses to cold
      exposure in fetuses, we conducted experiments on six goat fetuses, three aged 95
      116 d of gestation (dGA; group I), and three aged 122-134 dGA (group II), using
      an extrauterine fetal incubation system that provided arterio-venous
      extracorporeal membrane oxygenation (A-V ECMO). The fetuses were cannulated via
      the umbilical vessels, and their blood gas exchange was totally supported by A-V
      ECMO, while they were maintained in an isothermal incubator containing artificial
      amniotic fluid. After confirming that fetuses were in metabolically stable
      condition in the extrauterine incubation system, fetal core temperature was
      lowered by 2 degrees C over 2 h by decreasing the temperature of incubating fluid
      from 39.5 degrees C. During and after cold exposure, fetal heart rate and
      arterial blood pressure remained unchanged. We observed significant increases in
      oxygen consumption and plasma concentrations of norepinephrine, epinephrine,
      adrenocorticotropic hormone, and cortisol in group II but not in group I fetuses.
      In addition, based on regression analysis, maximal changes of these parameters
      during cold exposure were linearly correlated with gestational age significantly,
      and the regression lines were found to intersect the x (gestational age) axis at
      around 98-106 dGA. These results suggest that metabolic and endocrine responses
      to cold exposure develop with gestational age in the goat fetus, the responses
      being manifested around 100 dGA.

PMID- 9544998
TI  - Evidence that phenylalanine hydroxylation rates are overestimated in neonatal
      subjects receiving total parenteral nutrition with a high phenylalanine content.
AB  - Recent publications have indicated that the parenterally fed neonate has a
      substantial ability to hydroxylate phenylalanine. Examination of these data
      suggests that, at high phenylalanine intakes, estimated rates of hydroxylation
      exceed rates of intake. This implies significant net tissue breakdown. However,
      the quantitative validity of the estimates of phenylalanine hydroxylation cannot
      be assessed without nitrogen balance data. We have recently developed a
      parenterally fed neonatal piglet model and have used this to study aromatic amino
      acid metabolism in piglets fed different amino acid solutions. Reappraisal of the
      data from these studies has allowed us to estimate both phenylalanine
      hydroxylation and tissue protein accretion. Piglets were parenterally fed Vamin
      [292 micromol of Phe x kg(-1) x h(-1), 26 micromol of Tyr x kg(-1) x h(-1)],
      Vaminolact + Phe [VLP, 277 micromol of Phe x kg(-1) x h(-1), 26 micromol Tyr x
      kg(-1) x h(-1)], or Vaminolact + glycyl-L-tyrosine [VLGT, 152 micromol of Phe x
      kg(-1) x h(-1), 159 micromol of Tyr x kg(-1) x h(-1)] for 8 d. Nitrogen balance
      was measured over the last 5 study d, and aromatic amino acid kinetics were
      determined using a primed continuous infusion of L-[1-4C]phenylalanine on d 8.
      Average body protein gain, derived from nitrogen balance, was 11 g x kg(-1) x d(
      1). For the Vamin and VLP groups, the rates of phenylalanine hydroxylation were
      estimated to be 139 and 90% of intake, respectively. However, phenylalanine
      hydroxylation was only 16% of intake for the VLGT group. In view of the tissue
      protein accretion data, it appears that the rate of phenylalanine hydroxylation
      may be overestimated in neonates fed high phenylalanine parenteral nutrition. The
      extent to which the parenterally fed neonate can adapt to a high phenylalanine
      intake, by increasing the rate of phenylalanine hydroxylation, remains to be
      determined.

PMID- 9544999
TI  - Factors affecting the 2H to 18O dilution space ratio in infants.
AB  - In the doubly labeled water (DLW) method, for measurement of energy expenditure
      in humans, calculation of carbon dioxide production rate is influenced by the
      ratio (R) of the dilution spaces of the tracer isotopes 2H and 18O. Recent
      publications have recommended use of a fixed value for R, using a mean population
      value (meanR) rather than individually derived experimental values. However, most
      of the data considered previously were derived from adults. Infants are
      characterized by rapid rates of energy deposition and high body water content,
      either of which could influence isotope kinetics. We have considered whether use
      of a fixed R value is suitable for DLW studies of infants, and whether the adult
      (meanR) value is appropriate. Data from 281 DLW measurements in healthy infants
      aged 6 wk to 12 mo were analyzed. Mean R of all measurements was 1.036 (SD
      0.019), very similar to (meanR) values recommended for adults. We found
      analytical precision could account for almost all between-subject variation at a
      single time point. However, we also found relationships between R and age and
      weight gain, indicating that physiology does influence the space ratio. The
      effect of weight gain on R was negligible, but changes of (meanR) with age,
      reflecting changes in percentage body water during infancy, were of sufficient
      magnitude to affect calculation of energy expenditure significantly. Our analysis
      suggests that use of a fixed ratio at a single time point in infancy is
      acceptable, but that the appropriate value of (meanR) changes over the first year
      of life.

PMID- 9545000
TI  - Hyperprolactinemia, a tool in treatment control of tetrahydrobiopterin
      deficiency: endocrine studies in an affected girl.
AB  - Severe tetrahydrobiopterin (BH4) deficiency is a naturally occurring model of
      cerebral catecholamine and serotonin shortage. Examination of the stimulated
      release and physiologic secretion pattern of several hormones in affected
      individuals permits certain conclusions concerning the involvement of these
      neurotransmitters in hormone regulation. Treatment, moreover, permits the ranking
      of the quality of the therapeutic regimens in use according to the degree of
      hormonal alteration. The 24-h secretion pattern of prolactin, GH, cortisol, and
      melatonin and the stimulated release of prolactin, GH, TSH, and gonadotropins
      were studied in an affected girl. Severe hyperprolactinemia with disruption of
      the pulsatile and circadian secretion pattern was the prevailing feature. The GH
      physiologic secretion pattern was not affected, but its stimulation was impaired.
      Melatonin displayed a normal circadian secretion pattern; the rhythm, however,
      was advanced by several hours. Conventional treatment of BH4 deficiency, i.e.
      BH4, 5-hydroxytryptophan, and L-DOPA/carbidopa (the last named given in three
      doses per day), suppresses prolactin levels merely for a few hours. L
      DOPA/carbidopa given at shorter intervals or, even better, as a slow release
      preparation, is more effective in suppressing prolactin levels. Our data indicate
      immense hyperprolactinemia but few other hormonal disturbances in severe BH4
      deficiency. Prolactin secretion may serve as an extremely sensitive marker for
      the hypothalamic dopamine content under different therapeutic regimens. Treatment
      with an L-DOPA/carbidopa slow release preparation produces virtually normal
      prolactin levels.

PMID- 9545001
TI  - Growth, insulin-like growth factor I (IGF-I), and IGF-binding proteins 1 and 3 in
      children with severe liver disease before and after liver transplantation: a
      longitudinal and cross-sectional study.
AB  - We aimed to study the growth and growth factors of children with liver disease
      before and after liver transplantation (LT). Three observation intervals: 1)
      before LT (preLT), 2) after LT on daily prednisone treatment (dP), and 3) on
      alternate day prednisone (adP). A longitudinal study (LS) involved 17 infants (9
      male) aged 0.73-2.38 y at LT; mean (+/- SD) height (Ht) SD score (SDS) at LT was 
      2.02 (+/- 1.25). In a cross-sectional study, there were 123 children (73 male)
      aged 0.16-14.88 y (mean 3.72 y). IGF-I and IGF binding proteins (BP) 1 and 3 were
      measured at the same intervals. The results were, for LS, preLT height velocity
      (HV) SDS (X +/- SD -0.8+/-1.4) lower (p < 0.01) than adP-HV SDS (3.1+/-1.8) but
      not different from dP-HV SDS (-1.0+/-1.9). For the cross-sectional study, dP-Ht
      SDS (X+/-SD -1.94+/-1.31) lower (p < 0.001) than preLT-Ht SDS (-1.03+/-1.06) and
      adP-Ht SDS (-0.98+/-1.20). Parental target SDS was not different from adP-Ht SDS.
      (Similar observations were made in the LS.) The dP- sitting height (SH) and
      subischial leg length (SLL) SDS were significantly lower than both preLT- and adP
      SH SDS and SLL SDS (p = 0.02 and 0.002, respectively). There was a significant
      improvement of head circumference SDS and arm circumference SDS from preLT to
      adP. The dP and adP IGF-I and IGF-BP3 levels were greater than preLT levels (p <
      0.001); no differences were found between preLT, dP, and adP IGF-BP1 levels. We
      conclude that growth in children with liver disease does not improve after LT on
      dP, but catch-up growth is shown on adP, appearing to depend mainly on the
      clinical course and corticosteroid regimen. IGF-I and IGF-BP3 increment on dP
      (and sustained on adP) is possibly due to liver regeneration, in contrast with
      inhibition of body growth on dP, possibly due to central and peripheral effects
      of corticosteroid.

PMID- 9545002
TI  - Treatment with recombinant human growth hormone in short children with
      nephropathic cystinosis: no evidence for increased deterioration rate of renal
      function. The European Study Group on Growth Hormone Treatment in Short Children
      with Nephropathic Cystinosis.
AB  - To evaluate the effect of long-term treatment with recombinant human GH (rhGH) on
      renal function in short children with nephropathic cystinosis with and without
      concomitant cysteamine treatment, 36 growth-retarded children with nephropathic
      cystinosis (age 7.3+/-2.7 y; creatinine clearance [C(CR)] 50+/-27 mL (min x 1.73
      m2)(-1) were treated with 1 IU rhGH/kg/wk for up to 5 y. The rise in serum
      creatinine before and during rhGH treatment was compared with that in a
      historical control group of cystinotic patients. The effect of concomitant
      cysteamine treatment on the evolution of renal function before and after the
      start of rhGH was evaluated separately in patients without (group A) and with
      cysteamine treatment (group B). The decline of C(CR) was also compared with that
      in noncystinotic patients with chronic renal failure with and without rhGH
      treatment. At study entry, serum creatinine values in group A were similar to
      those in the historical controls, whereas group B had significantly lower serum
      creatinine values. Treatment with rhGH did not accelerate the rise in creatinine
      independently of cysteamine treatment. There were no significant differences in
      the mean decline of C(CR) per year in cystinotic compared with noncystinotic
      patients with chronic renal failure with or without rhGH treatment. rhGH therapy
      for up to 5 y does not accelerate the deterioration of renal function. This
      justifies the continuation of controlled studies of rhGH treatment in these
      patients. The study also provides further evidence that cysteamine therapy
      reduces the progression of renal failure in children with cystinosis.

PMID- 9545003
TI  - Effect of plasma from patients with idiopathic nephrotic syndrome on proteoglycan
      synthesis by human and rat glomerular cells.
AB  - In vivo and in vitro findings have shown that plasma of patients with idiopathic
      nephrotic syndrome (INS) contain factors that increase glomerular permeability to
      proteins. The effects of these factors on proteoglycan synthesis by glomerular
      cells are unknown. To investigate the effect of plasma from patients with INS (n
      = 23) and other glomerulopathies (n = 12) on the amount of proteoglycans
      synthesized by cultured rat mesangial cells and human glomerular epithelial
      cells, glomerular cells were cultured for 24 h with plasma from patients or
      control subjects, and incorporation of Na2(35)SO4 in chondroitin dermatan sulfate
      and heparan sulfate was assessed using a cationic nylon membrane. The mean ratio
      of glycosaminoglycan produced by rat mesangial cells when in contact with plasma
      (5%) from INS patients to the amount produced when in contact with control plasma
      was 0.70+/-0.06. The mean ratio of heparan sulfate was 0.58+/-0.08. The decrease
      of heparan sulfate production was present in the cellular and in the
      extracellular fraction. It was observed when the cells were in contact with
      plasma from patients in relapse but not when in remission. No decrease of heparan
      sulfate production was observed with four of the five patients with membranous
      glomerulonephritis (ratio of 1.27+/-0.03), IgA nephropathy (n = 5, ratio of
      1.27+/-0.03), and membranoproliferative glomerulonephritis (n = 2, ratio of
      1.39+/-0.34). When human glomerular epithelial cells were exposed to 5% plasma
      from INS patients in relapse (n = 9), the mean ratio of heparan sulfate was
      0.62+/-0.06 in the cellular fraction and 0.72+/-0.08 in the medium. When in
      contact with plasma from patients in remission, no difference of
      glycosaminoglycan production was observed. A factor present in plasma from
      patients with INS during initial episodes or relapses is able to decrease the
      proteoglycan production of glomerular cells.

PMID- 9545005
TI  - Quantitative correlation between globin mRNAs and synthesis of fetal and adult
      hemoglobins during hemoglobin switchover in the perinatal period.
AB  - To determine whether a quantitative relationship existed between globin mRNAs and
      their translation products during the period of switchover, the relative amounts
      of the mRNAs of alpha-, beta-, and gamma-globins and their protein synthesis in
      cord blood samples were measured and compared. The synthesis of globins in
      immature red cells was measured by the incorporation of [3H]leucine followed by
      separation and quantitation of the polypeptides on a C4-reverse phase HPLC. The
      relative proportions of the mRNAs of globins were determined by RNase protection
      assay. A comparison of cord blood samples from 45 newborn infants of different
      gestational ages (25-41 wk; birth weight, 850-4695 g) revealed a very significant
      correlation (r2 = 0.924) between the ratio of globin mRNAs encoding HbF
      ([gamma/(gamma + beta)] mRNAs) and HbA ([beta/(gamma + beta)] mRNAs) and the
      ratio of de novo synthesis of HbF [gamma/(gamma + beta)] and HbA [beta/(gamma +
      beta)]. There was a linear relationship between the proportions of globin mRNAs
      encoding HbF with the proportional synthesis of HbF throughout the developmental
      stage studied. The ratio of alpha2/alpha1-globin mRNAs increased from 2.0 +/- 0.2
      between 24 and 36 wk of gestation to 2.3+/-0.4 (p = 0.02) during 37-41 wk of
      gestation. These results of the complementary changes at alpha- and beta-loci
      during fetal development may further the understanding of the coordinated
      regulation of globin gene expression.

PMID- 9545004
TI  - Characterization of early activation events in cord blood B cells after
      stimulation with T cell-independent activators.
AB  - Human neonates are immunologically immature, particularly in their humoral
      antibody responses to T cell-independent antigens, as exemplified by their
      increased susceptibility to infections with polysaccharide-encapsulated bacteria.
      To clarify the mechanism(s) underlying the unresponsiveness of neonates to
      polysaccharide antigens, we used an in vitro model with neonatal cord blood cells
      that has been shown to mimic surface Ig-dependent signaling in the adult by T
      cell-independent antigens. We studied the ability of cord blood human B cells to
      become activated after ligation of their surface Ig by unconjugated anti-Ig,
      dextran-conjugated anti-Ig, and Staphylococcus aureus Cowan A1, and compared
      their response with that of adult B cells. After the addition of nanogram
      concentrations of anti-Ig-dextran, neonatal cord blood B cells proliferated at
      levels comparable to that observed with adult B cells. The majority of cord blood
      B cells showed a marked rise in intracellular calcium, increased surface
      expression of human leukocyte antigen DR, and an increase in cell size. Direct
      activation of protein kinase C by phorbol esters in neonatal B cells led to
      cellular proliferation, and when combined with anti-Ig, a synergistic effect on
      proliferation was observed. These data suggest that the unresponsiveness of human
      neonates to polysaccharide antigens does not represent an inability of these
      antigens to induce early activation events in circulating B cells.

PMID- 9545006
TI  - Human choriocarcinoma JAR cells constitutively express pro-interleukin-1beta that
      can be released with Fc(gamma) receptor engagement.
AB  - Some authors have suggested that fetally derived syncytiotrophoblasts, which form
      the barrier between mother and the fetus, are an integral part of a complex
      macrophage-cytokine network involving maternal leukocytes, decidual cells,
      placental tissues, and even the fetus itself. We report here that
      syncytiotrophoblast-like JAR cells, a human choriocarcinoma cell line, share
      another feature common to cells of the monocyte-macrophage lineage, the ability
      to secrete IL-1beta when stimulated through their Fc(gamma) receptors. We
      incubated JAR cells with physiologically relevant concentrations of model BSA
      rabbit IgG-anti-BSA immune complexes or monomeric rabbit IgG for periods of up to
      72 h. Both monomeric IgG and immune complexes induced IL-1beta from JAR cells,
      although levels produced by immune complexes were approximately twice those
      induced by monomeric IgG. IL-1beta secretion was not inhibited by cycloheximide,
      and Western blots of JAR cell lysates using pro-IL-1beta MAb revealed
      constitutive expression of a 31-kD protein, whose levels declined within 2 h of
      stimulation by either IgG or immune complexes, but returned to baseline within 18
      h.

PMID- 9545007
TI  - Responses to pulsatile flow in piglet isolated cerebral arteries.
AB  - Because cerebrovascular hemorrhage in newborns is often associated with
      fluctuations in cerebral blood flow, this study was designed to investigate the
      effects of pulsatile flow in isolated cerebral arteries from neonatal piglets.
      Arteries mounted on cannulas were bathed in and perfused with a physiologic
      saline solution. An electronic system produced pulsations, the amplitude and
      frequency of which were independently controlled. At constant mean transmural
      pressure (20 mm Hg), increasing flow in steps from 0 to 1.6 mL/min under steady
      flow conditions caused a biphasic response, constriction at low flow, and
      dilation at high flow. Under pulsatile flow conditions (pulse amplitude 16-24 mm
      Hg; 2 Hz), the arteries dilated upon flow initiation and continued to dilate as
      mean flow increased. Dilation to pulsatile flow did not depend on the level of
      mean flow because switching from steady to pulsatile flow at each flow step also
      caused dilation. Arteries dilated further upon increasing either pulse amplitude
      (12-28 mm Hg; 2 Hz) or frequency (16-24 mm Hg; 4 Hz). Inhibiting nitric oxide
      synthesis with Nomega-nitro-L-arginine or perfusing with glutaraldehyde to
      decrease endothelial cell deformability significantly reduced dilations to
      pulsatile flow and to increased amplitude and frequency. These data suggest that
      the arterial response to flow is highly dependent on the mode of flow. Dilation
      induced by initiating pulsatile flow or increasing either pulse amplitude or
      frequency appears to be mediated by augmented nitric oxide release as result of
      shear stress-induced deformation of the endothelial cells.

PMID- 9545008
TI  - Pressure overload induced in newborn rats: effects on left ventricular growth,
      morphology, and function.
AB  - Gradual pressure overload was induced by abdominal aortic constriction in male
      rats on postnatal d 6 (AC6) or 2 (AC2). At the age of 8 wk, the systemic blood
      pressure was measured, and the contractile performance of the left ventricle (LV)
      was assessed after acute ligation of the ascending aorta in open chest
      anesthetized animals. The LV free wall was used for the determination of collagen
      concentration and morphometric analysis of cardiac myocytes and capillaries.
      Aortic constriction resulted in LV hypertrophy, which was more pronounced in AC2
      (by 71%) as compared with AC6 (by 34%) groups and correlated closely with the
      degree of pressure overload (r = 0.88 and 0.80, respectively). The right
      ventricular weight was increased by 13% in the AC2 group only. Contractile
      performance of the LV of aortic constricted rats was significantly higher before
      as well as after the acute load, but the average functional reserve was unchanged
      in both experimental groups. Although the maximum value of the rate of pressure
      development increased linearly with the degree of ventricular hypertrophy in the
      AC6 group (r = 0.82), a negative correlation was observed in the AC2 animals (r =
      -0.61). The density of myocytes was decreased, and the calculated average myocyte
      cross-sectional area was increased in aortic constricted rats, but the coronary
      capillary density and myocardial concentration of collagen remained constant.
      Thus, in spite of the larger cardiac growth response in the younger age group,
      the capillary proliferation and collagen formation were proportional to the
      ventricular hypertrophy. Therefore, the degrees of overload and hypertrophy do
      not seem to be limiting factors. Pressure overload induced in newborn rats can be
      a useful model for the study of mechanisms that control either the growth and
      differentiation of myocardium soon after birth, as well as the transition from
      compensated to decompensated hypertrophy at later stages.

PMID- 9545009
TI  - The relationship between temperature and calcium in acute cell damage after
      exposure to radiofrequency or thermal energy in isolated neonatal and adult
      rabbit cardiac myocytes.
AB  - Radiofrequency (RF) ablation is a nonsurgical technique using catheter-directed
      RF energy for treating cardiac arrhythmias in children and adults. Previous
      reports have suggested that sequestration of calcium (Ca2+) by the sarcoplasmic
      reticulum may partially protect mature cardiac myocytes from the effects of RF
      energy. The purposes of this study were to determine whether differences exist
      between neonatal and adult myocyte responses to RF energy and if myocyte damage
      is a Ca2+-dependent process. Because immature myocardium is functionally
      deficient in sarcoplasmic reticulum, we hypothesized that immature myocytes would
      be more susceptible to damage induced by RF energy. Isolated ventricular myocytes
      were obtained from neonatal and adult New Zealand White rabbits by enzymatic
      dissociation, then placed in a perfusion chamber designed to deliver RF energy or
      a heated perfusate solution. Measurements of bath temperature, cell morphology,
      and contractile response to electrical stimuli were recorded. RF energy
      application associated with increased perfusate temperature resulted in cell
      death, but not when the temperature rise was inhibited. Thus, the acute damage to
      cells exposed to RF energy appears to be mediated by thermal energy. After
      exposure to thermal energy, neonatal cells underwent contracture at lower
      temperatures than did adult cells. Perfusion with solutions containing low Ca2+
      concentrations, comparable to intracellular diastolic Ca2+ levels, had a
      protective effect for both neonatal and adult myocytes. These findings indicate
      that acute cell damage after exposure to RF energy is mediated by a Ca2+
      dependent process. Furthermore, immature myocardium is particularly susceptible
      to RF-mediated cell damage, possibly secondary to reduced Ca2+ sequestration by
      the sarcoplasmic reticulum.

PMID- 9545010
TI  - Experimental study of coil embolization using a new atelocollagen spring coil.
AB  - Spring steel coils have been used to occlude abnormal vessels in patients with a
      congenital heart malformation. However, long-term adverse effects of steel spring
      coils remain uncertain, although some long-term results appear to be good. The
      purpose of this study was to evaluate the angiographic and histologic results of
      coil embolization experimentally using a biodegradable atelocollagen coil that we
      have recently developed. The spring coil was made from a 30% atelocollagen
      solution mixed with a contrast medium. The delivery system consisted of a 5-F end
      hole catheter and a 3-F modified biotome catheter as a catch and release system.
      Coil embolization was percutaneously attempted in 12 dogs, and only one coil was
      placed in each dog so that a variety of endothelial coverage could be evaluated
      both in complete and incomplete occlusion. At 1 wk to 5 mo after the procedure,
      the occluded vessels were resected and examined histologically. Postprocedural
      angiography showed complete occlusion in 6 of the 12 vessels and partial
      occlusion in 6. Follow-up angiography showed complete occlusion in 8 and
      incomplete occlusion in 4. Histologic examination revealed that diffuse
      thrombosis around the coil loops and the exchange between blood and contrast
      medium were detectable as early as 7 d after embolization. Atelocollagen was
      gradually replaced with fibrous tissue and became markedly degraded by 5 mo.
      Atelocollagen spring coils can be used to occlude abnormal vessel effectively and
      safely. The histologic reactions and the fate of the coil seem to be within
      tolerable limits. This experimental study supports the feasibility of a clinical
      trial of this coil embolization in patients with an aorticopulmonary collateral
      artery.

PMID- 9545011
TI  - Impaired gas mixing and low lung volume in preterm infants with mild chronic lung
      disease.
AB  - The aim of this study was to assess the possible role of gas mixing inefficiency
      in spontaneously breathing infants with mild chronic lung disease (CLD) of
      prematurity in relation to changes in other functional parameters. A simple
      bedside technique for recording and analysis of multiple breath nitrogen washout
      curves was applied together with occlusion mechanics. Fifteen preterm infants
      with mild or moderately severe CLD were studied at a mean postconceptional age of
      35 wk, together with 15 healthy preterm infants at the same maturity. All infants
      breathed spontaneously, and the test was performed by a continuous bypass flow
      system, connected to a face mask, a pneumotachograph, and a nitrogen meter. The
      results showed impaired gas mixing with moment ratios above the 95th percentile
      of the normal group in 11/15 infants with CLD. Functional residual capacity (FRC)
      was low in 13/15 infants, but specific compliance and resistance of the
      respiratory system did not differ between the groups. As FRC and moment ratios
      were not correlated, it is suggested that they may reflect different aspects of
      the pathophysiology in CLD. It is concluded that low FRC and disturbed gas mixing
      are characteristic disturbances in CLD at different degrees of severity. The
      multiple breath nitrogen washout test, followed by moment analysis of end-tidal
      nitrogen concentrations, is a simple and sensitive method for detection of these
      disturbances and for monitoring purposes.

PMID- 9545012
TI  - Surfactant versus saline as a vehicle for corticosteroid delivery to the lungs of
      ventilated rabbits.
AB  - Local administration of steroids to the lungs in ventilated newborn infants can
      minimize the harmful side effects that occur with systemic administration. An
      efficient system of drug delivery that provides uniform distribution within the
      lungs is essential for the treatment of bronchopulmonary dysplasia. In this study
      we compare surfactant with 0.9% saline solution as vehicles for the direct
      instillation of a steroid (budesonide) into the lungs. Twenty-two anesthetized,
      ventilated rabbits received [3H]budesonide in either 0.9% saline or surfactant,
      administered through an endotracheal tube. Before drug administration, bronchial
      lavage was performed on half of the animals to serve as a model for surfactant
      deficiency. Lung samples were analyzed by both autoradiography (alveolar versus
      airway distribution) and liquid scintillation counting (central versus peripheral
      deposition). As expected, the delivered concentration of [3H]budesonide decreased
      as airway size decreased and branching increased. Significantly less
      [3H]budesonide was deposited in the alveolar spaces of all study groups compared
      with that deposited in the small and large airways (p < 0.05). However, both
      vehicles were equally efficient in delivering [3H]budesonide to the lungs.
      Although the alveolar and peripheral areas received less (4-11%) of the drug than
      the central tissue (14-28%), this was consistent among all the groups and was not
      affected by altered lung compliance. Therefore, either surfactant or saline could
      be used to efficiently and reliably deliver budesonide to the lungs at a level
      greater than that reported using nebulizers. Because normal saline is currently
      used for tracheal toilette, it is likely to be preferred considering the
      increased costs associated with surfactant.

PMID- 9545013
TI  - Potassium channels in human fetal airway smooth muscle cells.
AB  - Ion channels underlying the resting membrane potential were examined in human
      fetal airway smooth muscle (ASM). Tissue was obtained from the Medical Research
      Council Tissue Bank, London, UK. ASM cells were enzymatically dispersed, and ion
      currents were examined using a patch clamp. Although all cells were of similar
      size and stained intensely for vimentin, only approximately 50% stained intensely
      for smooth muscle alpha-actin or myosin heavy chain. Depolarization induced a
      tetraethylammonium (TEA)- and charybdotoxin (ChTX)-sensitive outward current that
      varied widely among cells (<50 to >2000 pA at +100 mV), and a smaller
      nonselective cation current that was similar in all cells (approximately 20 pA at
      +100 mV). The TEA-sensitive current was associated with three types of large
      conductance, ChTX-sensitive K+ channel: a 200-pS channel, which was active at
      negative potentials and low [Ca2+], as described for freshly isolated adult ASM,
      and two other K+ channels of 100 and 150 pS, previously observed only in adult
      ASM proliferating in culture. ChTX, but not 4-aminopyridine, caused a substantial
      depolarization in the current clamp mode, suggesting that, in contrast to ASM
      from other species or vascular smooth muscle, large conductance K+ channels
      rather than a delayed rectifier are the major determinant of membrane potential
      in this tissue. Our results show a distinct similarity between fetal ASM and
      adult ASM proliferating in culture. We suggest that the heterogeneity in current
      density and staining reflect different degrees of differentiation, rather than
      different cell types, and that the 100- and 150-pS K+ channels are specifically
      associated with a proliferative phenotype in human ASM.

PMID- 9545014
TI  - Presence of thyrotropin receptor in infant adipocytes.
AB  - In healthy infants, the levels of TSH are known to peak at 50-100 times adult
      values during the first days of life. In studies of isolated human infant
      adipocytes, we have earlier shown that bovine TSH (bTSH) has a strong lipolytic
      effect, accompanied by a blunted response of adipocytes to catecholamines. In
      this study, we used human recombinant TSH (hTSH), and incubation of adipocytes
      with hTSH induced a lipolytic response similar to that obtained with the beta
      adrenergic receptor agonist isoprenaline in adipocytes isolated from three
      infants. The lipolytic effect of hTSH was completely blocked by inhibitory TSH
      receptor (TSHR) antibodies. The TSHR mediates the effects of TSH in the thyroid,
      and it has been detected in some extrathyroid tissues, but not in isolated human
      adipocytes or childhood adipose tissue. In this study, we found TSHR RNA in
      infant and adult adipose tissues and isolated adipocytes with reverse
      transcriptase-PCR. The sequence of the amplified PCR product agreed with the
      published sequence. Northern blot hybridization on RNA prepared from infant
      adipose tissue showed a transcript of the expected size, and the expression of
      TSHR seemed higher in infant than in adult adipose tissue. In conclusion, this
      study indicates that TSH plays an active role in the metabolic adaptation after
      birth.

PMID- 9545015
TI  - Current estimates of the economic cost of obesity in the United States.
AB  - This study was undertaken to update and revise the estimate of the economic
      impact of obesity in the United States. A prevalence-based approach to the cost
      of illness was used to estimate the economic costs in 1995 dollars attributable
      to obesity for type 2 diabetes mellitus, coronary heart disease (CHD),
      hypertension, gallbladder disease, breast, endometrial and colon cancer, and
      osteoarthritis. Additionally and independently, excess physician visits, work
      lost days, restricted activity, and bed-days attributable to obesity were
      analyzed cross-sectionally using the 1988 and 1994 National Health Interview
      Survey (NHIS). Direct (personal health care, hospital care, physician services,
      allied health services, and medications) and indirect costs (lost output as a
      result of a reduction or cessation of productivity due to morbidity or mortality)
      are from published reports and inflated to 1995 dollars using the medical
      component of the consumer price index (CPI) for direct cost and the all-items CPI
      for indirect cost. Population-attributable risk percents (PAR%) are estimated
      from large prospective studies. Excess work-lost days, restricted activity, bed
      days, and physician visits are estimated from 88,262 U.S. citizens who
      participated in the 1988 NHIS and 80,261 who participated in the 1994 NHIS.
      Sample weights have been incorporated into the NHIS analyses, making these data
      generalizable to the U.S. population. The total cost attributable to obesity
      amounted to $99.2 billion dollars in 1995. Approximately $51.64 billion of those
      dollars were direct medical costs. Using the 1994 NHIS data, cost of lost
      productivity attributed to obesity (BMI> or =30) was $3.9 billion and reflected
      39.2 million days of lost work. In addition, 239 million restricted-activity
      days, 89.5 million bed-days, and 62.6 million physician visits were attributable
      to obesity in 1994. Compared with 1988 NHIS data, in 1994 the number of
      restricted-activity days (36%), bed-days (28%), and work-lost days (50%)
      increased substantially. The number of physician visits attributed to obesity
      increased 88% from 1988 to 1994. The economic and personal health costs of
      overweight and obesity are enormous and compromise the health of the United
      States. The direct costs associated with obesity represent 5.7% of our National
      Health Expenditure in the United States.

PMID- 9545016
TI  - Evidence for multiple determinants of the body mass index: the National Heart,
      Lung, and Blood Institute Family Heart Study.
AB  - The body mass index (BMI) is a complex phenotype representing the amount of fat
      mass, lean mass, body build and proportions, and it is likely to be affected by
      various metabolic processes, hormonal effects, energy intake and expenditure, and
      interactions within and among these broad categories of etiologic factors.
      Nonetheless, several previous studies have reported evidence for major gene
      segregation for the BMI in various populations. Data on a random sample of
      Caucasian families participating in the National Heart, Lung, and Blood Institute
      (NHLBI) Family Heart Study were analyzed to document the extent of familial
      resemblance and to investigate whether a similar monogenic inheritance pattern
      could be detected. Genetic analysis was carried out on age- and sex-adjusted BMI
      values. Familial correlations were significant implying a maximal heritability,
      including all genetic and environmentally inherited additive factors, of 41% to
      59%. Segregation analysis revealed the presence of two maximum likelihood
      solutions, one characterized as a recessive Mendelian gene and the other as a
      major effect with an ambiguous transmission pattern. The presence of two such
      solutions is consistent with detection of two separate factors, each influencing
      the BMI distribution in a substantive manner. The evidence also supports a
      multifactorial background for BMI and suggests that the frequencies of these two
      factors, one of which appears to be a gene, may vary among diverse populations in
      the United States.

PMID- 9545017
TI  - Effects of sibutramine on resting metabolic rate and weight loss in overweight
      women.
AB  - Sibutramine, a monoamine re-uptake inhibitor, has recently been approved by the
      Food and Drug Administration as a weight loss agent. Sibutramine lowers
      bodyweight in rodents by reducing energy intake and increasing energy
      expenditure. Sibutramine facilitates weight loss in human subjects, but it is not
      clear whether it acts on energy intake, energy expenditure, or both. The present
      study was a randomized clinical trial designed to assess the effects of
      sibutramine (at 10 or 30 mg/day) on body weight and resting metabolic rate (RMR).
      Forty-four overweight women were randomized to 1) placebo (n=15); 2) sibutramine
      at 10 mg/day (n=15) or, 3) sibutramine at 30 mg/day (n=14). All subjects were
      instructed to consume a 1200 kcal/day diet for 8 weeks while receiving drug or
      placebo. RMR was assessed by indirect calorimetry at baseline, at 3 hours after
      the first dose of drug (or placebo), and at the end of the 8-week weight-loss
      period. Sibutramine reduced body weight-relative to placebo, but there was no
      difference between weight loss on the two sibutramine doses. No significant
      differences in RMR between sibutramine and placebo were seen, either 3-hour post
      dose or after the 8-week weight-loss period. After the weight loss period, all
      groups were taken off medication and kept weight stable for another 4 weeks. RMR
      was measured again and was not different among groups. That there was no change
      in RMR when sibutramine was stopped further suggests that the drug does not
      directly affect RMR. In summary, while sibutramine was shown to be an effective
      weight-loss agent over 8 weeks, we found no evidence that it increased RMR.

PMID- 9545018
TI  - Leptin receptor gene in a large cohort of massively obese subjects: no indication
      of the fa/fa rat mutation. Detection of an intronic variant with no association
      with obesity.
AB  - The massive obesity caused in rodents by the disruption of the leptin-receptor
      signal through genetic defects at the level of either leptin (OB) or leptin
      receptor (OB-R) has raised the question of the relevance of these genes to morbid
      obesity in humans. In this study, we screened a large population of massively
      obese subjects for the presence of a leptin receptor mutation homologous to that
      of fa/fa rats, a single base substitution changing glutamine 269, a highly
      conserved glutamine found at position 270 in the human sequence. After polymerase
      chain reaction (PCR) amplification of a DNA region encompassing the end of exon
      5, intron 5, and the beginning of exon 6, we performed restriction fragment
      length polymorphism analysis. Within the limitations of this approach where only
      mutations introducing restriction sites (5 of 8 possibilities) could be assessed,
      no evidence of mutation at the codon gln 270 was found in 343 massively obese
      subjects. However, a new OB-R gene variant in intron 5 was revealed by MaeII
      digestion of the PCR products. MaeII/hOB-R genotyping revealed no difference in
      the distribution of the genotypes between obese subjects and a group of 79
      unrelated nonobese control subjects. In addition, no significant association
      between various obesity-related metabolic phenotypes and the presence of
      MaeII/hOB-R alleles was found. Thus, our results did not support a significant
      role for the MaeII/hOB-R gene variant in the development of the obese phenotype
      in the population we studied.

PMID- 9545019
TI  - Relationship of leptin concentration to gender, menopause, age, diabetes, and fat
      mass in African Americans.
AB  - This investigation was designed to determine the relationship of leptin
      concentration to gender, sex hormones, menopause, age, diabetes, and fat mass in
      African Americans. Participants included 101 African Americans, 38 men (mean age,
      34.2 +/- 7.4 years), 29 age-matched premenopausal women (mean age, 32.6 +/- 3.7
      years), and 36 postmenopausal women (mean age, 57.8 +/- 5.9 years). The women
      were not taking exogenous sex hormones, and 12 subjects were diabetic. Percent
      body fat was calculated with the Siri formula, fat mass (FM) was calculated as
      weight x percent body fat, and Fat-free mass (FFM) was calculated as weight minus
      FM. Fasting plasma was assayed for leptin, estradiol, free testosterone, glucose,
      and insulin concentrations. The nondiabetics had an oral glucose tolerance test
      (OGTT). The diabetics compared with the non-diabetics had a higher central fat
      index (p=0.04) but otherwise were similar to nondiabetics in all parameters
      measured. Body mass index, percent body fat, and FM were greater in women than
      men (p<0.001). Leptin concentrations in men, premenopausal, and postmenopausal
      women were: 7.51 +/- 8.5, 33.9 +/- 17.3, 31.4 +/- 22.3 ng/mL. Leptin/FM x 100 in
      the three groups were: 28.9 +/- 16.1, 98.65 +/- 44.9, 77.1 +/- 44.5 ng/mL/kg. The
      gender difference in leptin concentration and leptin/FM was significant
      (p<0.001), but the difference between premenopausal and postmenopausal women was
      not. In each group, weight, percent body fat, and FM were highly correlated with
      leptin concentration. Multiple regression analyses with leptin concentration as
      the dependent variable and age, diabetic status, percent body fat, weight, FM,
      FFM, estradiol, and free testosterone concentrations as independent variables
      demonstrated that the determinants of leptin concentration in men was weight only
      (R=0.83, p<0.001), in premenopausal women it was FM only (R=0.57, p<0.001), and
      in postmenopausal women it was weight only (R=0.67, p<0.001). With diabetics
      excluded, the multiple regression analysis was repeated with fasting insulin
      concentration and the area under the insulin curve during the OGTT included as
      independent variables. The results for this multiple regression analyses were the
      same as the first. Therefore, leptin concentration in African Americans is
      determined by gender and fat mass. Menopause, age, and diabetes do not affect
      leptin concentration.

PMID- 9545020
TI  - Demand characteristics of the research setting can influence indexes of negative
      affect-induced eating in obese individuals.
AB  - Measures of negative affect-induced eating (NAIE) are common in clinical research
      with obese individuals. However, previous studies suggest that measures of NAIE
      can be induced by social desirability tendencies or demand characteristics of the
      research setting. Using an experimental design, the present study tested the
      effects of demand characteristics of the research setting on self-report and
      behavioral indexes of NAIE. Obese and nonobese subjects (n=107) were randomly
      assigned to an experimental or control group. Experimental subjects received a
      lecture indicating an association between emotional eating and obesity; control
      subjects received no information. Outcome measures were indexes of NAIE from a
      questionnaire, food diaries, and food intake during a laboratory "taste test." We
      hypothesized that the association between relative body mass and NAIE would be
      stronger among subjects receiving the lecture manipulation than control subjects.
      Results indicated that NAIE indexes, particularly from food diaries, were
      influenced modestly by research demand characteristics. We conclude that demand
      characteristics of the research setting can affect indexes of NAIE among obese
      persons.

PMID- 9545021
TI  - Composition of dietary fat affects blood pressure and insulin responses to
      dietary obesity in the dog.
AB  - Cardiovascular and metabolic parameters were evaluated in 15 female spayed dogs
      before and after they became obese on either a saturated fat (LD, lard, n=8) or
      unsaturated fat (CO, corn oil, n=7) diet. Body weight and body fat increased
      significantly in both groups, although no differences occurred between diet
      groups. Dogs receiving the LD diet exhibited a greater increase in mean arterial
      pressure than those receiving the CO diet (p<0.01; 15.9 +/- 2.1 vs. 9.8 +/- 3.3
      mm Hg increase). The CO diet stimulated a greater increase in heart rate than the
      LD diet (p<0.05; 32.8 +/- 7.8 vs. 14.1 +/- 5.8 bpm increase). Ganglionic blockade
      with chlorisondamine caused an increase in HR in both lean groups and in the
      obese CO group, but not the obese LD group, consistent with a decrease in
      parasympathetic tone to the heart in the dogs overfed saturated fat. Obesity
      enhanced the heart rate response to beta-adrenergic stimulation by isoproterenol
      in the LD, but not CO group. The LD diet increased circulating insulin and
      decreased insulin sensitivity, whereas the CO diet had no effect on either
      parameter. These findings suggest that the composition of dietary fat can
      modulate the autonomic and metabolic adaptations induced by dietary obesity.

PMID- 9545022
TI  - Effect of chronic central administration of glucagon-like peptide-1 (7-36) amide
      on food consumption and body weight in normal and obese rats.
AB  - Glucagon-like peptide (7-36) amide (GLP-1) acutely inhibits food and water
      consumption in rats after intracerebroventricular (icv) administration. To assess
      the potential for desensitization of these effects, we investigated the effects
      of chronic icv administration of GLP-1 on food consumption and body weight in
      Sprague-Dawley (SD) rats and Zucker (fa/fa) obese rats. In vitro functional
      densensitization of the GLP-1 receptor was not observed after overnight exposure
      of Rin m5F insulinoma cells to GLP-1 at concentrations up to 10 nM.
      Administration of GLP-1 to SD rats (30 microg icv twice a day for 6 days)
      resulted in significant reductions in 24-hour food consumption each day (25 +/-
      1%). Continuous icv infusion of GLP-1 for 7 and 14 days significantly inhibited
      cumulative food consumption and reduced body weight in SD rats. In the
      genetically obese Zucker rat, chronic dosing with GLP-1 (30 microg icv) once a
      day for 6 days caused significant reductions in food consumption each day and a
      reduction in body weight. These results indicate that the GLP-1 pathways in the
      central nervous system controlling food consumption do not desensitize after
      chronic exposure to GLP-1 and suggest that agonists of the central GLP-1 receptor
      may be effective agents for the treatment of obesity.

PMID- 9545023
TI  - The effect of glucose concentration on insulin-induced 3T3-L1 adipose cell
      differentiation.
AB  - We examined the effect of glucose concentration on insulin-induced 3T3-L1 adipose
      cell differentiation. Oil Red O staining of neutral lipid, cellular triglyceride
      mass, and glycerol phosphate dehydrogenase (GPDH) activity, were greater in 3T3
      L1 cells cultured at 5 mM vs. 25 mM glucose. GPDH activity was 2- to 4-fold
      higher at 5 mM vs. 25 mM glucose over a range of insulin concentrations (0.1 to
      100 nM). Insulin-stimulated tyrosine phosphorylation of insulin receptor
      substrate-1 (IRS-1) was 1.7-fold greater, and insulin-stimulated phosphoinositide
      3-kinase association with IRS-1 was 2.3-fold higher, at 5 mM vs. 25 mM glucose.
      These effects of glucose were not caused by alterations in IRS-1 mass or cell
      surface insulin binding. In preadipose cells at 5 mM glucose, expression of the
      leukocyte antigen-related (LAR) protein tyrosine phosphatase (negative regulator
      of insulin signaling) was 63% of the level at 25 mM glucose. Our data demonstrate
      that glucose concentration affects insulin-induced 3T3-L1 adipose cell
      differentiation as well as differentiation-directed insulin signaling pathways.
      Alterations in LAR expression potentially may be involved in modulating these
      responses.

PMID- 9545024
TI  - Hormonal regulation of leptin mRNA expression and preadipocyte recruitment and
      differentiation in porcine primary cultures of S-V cells.
AB  - The hormonal regulation of leptin mRNA expression and the association between
      leptin expression and adipocyte differentiation were examined in primary cultures
      of porcine S-V cells with Northern blot and immunocytochemical analysis. Seeding
      for 3 days with fetal bovine serum (FBS) with varying levels of dexamethasone
      (Dex) increased levels of leptin mRNA in a dose-dependent manner in parallel with
      increases in the proportion of preadipocytes (AD-3 positive cells; AD-3, a
      preadipocyte marker). Six-day treatment with 10 or 850 nM insulin after FBS+Dex
      treatment resulted in a similar increase in leptin mRNA expression and
      morphological differentiation. However, significantly lower levels of leptin mRNA
      and smaller fat cells were observed in cultures treated with 1 nM insulin or 10
      nM insulin-like growth factor-I (IGF-I). Dex-induced increases in leptin mRNA
      levels and AD-3 cell numbers were blocked completely by the addition of
      transforming growth factor-beta (TGF-beta) to FBS+Dex-treated cultures. However
      TGF-beta significantly increased fat cell size and leptin mRNA expression when
      added to ITS (insulin, 850 nM; transferrin, 5 microg/ml; and selenium, 5
      microg/mL) treated cultures during the lipid-filling stage. When added with
      FBS+DEX for the first 3 days, growth hormone (GH) did not influence the Dex
      induced increase in AD-3 cells and leptin mRNA expression, but GH reduced leptin
      mRNA levels when added with insulin for 6 days after FBS+Dex. These results
      demonstrated that regulation of leptin mRNA expression by Dex, insulin, IGF-I,
      TGF-beta, and GH may be associated with changes in preadipocyte number and fat
      cell size.

PMID- 9545025
TI  - The economic impact of obesity in the United States: whither?

PMID- 9545026
TI  - Twisting DNA molecules.

PMID- 9545027
TI  - Compliant realignment of binding sites in muscle: transient behavior and
      mechanical tuning.
AB  - The presence of compliance in the lattice of filaments in muscle raises a number
      of concerns about how one accounts for force generation in the context of the
      cross-bridge cycle--binding site motions and coupling between cross-bridges
      confound more traditional analyses. To explore these issues, we developed a
      spatially explicit, mechanochemical model of skeletal muscle contraction. With a
      simple three-state model of the cross-bridge cycle, we used a Monte Carlo
      simulation to compute the instantaneous balance of forces throughout the filament
      lattice, accounting for both thin and thick filament distortions in response to
      cross-bridge forces. This approach is compared to more traditional mass action
      kinetic models (in the form of coupled partial differential equations) that
      assume filament inextensibility. We also monitored instantaneous force
      generation, ATP utilization, and the dynamics of the cross-bridge cycle in
      simulations of step changes in length and variations in shortening velocity.
      Three critical results emerge from our analyses: 1) there is a significant
      realignment of actin-binding sites in response to cross-bridge forces, 2) this
      realignment recruits additional cross-bridge binding, and 3) we predict
      mechanical behaviors that are consistent with experimental results for velocity
      and length transients. Binding site realignment depends on the relative
      compliance of the filament lattice and cross-bridges, and within the measured
      range of these parameters, gives rise to a sharply tuned peak for force
      generation. Such mechanical tuning at the molecular level is the result of
      mechanical coupling between individual cross-bridges, mediated by thick filament
      deformations, and the resultant realignment of binding sites on the thin
      filament.

PMID- 9545028
TI  - Structure and dynamics of calmodulin in solution.
AB  - To characterize the dynamic behavior of calmodulin in solution, we have carried
      out molecular dynamics (MD) simulations of the Ca2+-loaded structure. The crystal
      structure of calmodulin was placed in a solvent sphere of radius 44 A, and 6 Cl-
      and 22 Na+ ions were included to neutralize the system and to model a 150 mM salt
      concentration. The total number of atoms was 32,867. During the 3-ns simulation,
      the structure exhibits large conformational changes on the nanosecond time scale.
      The central alpha-helix, which has been shown to unwind locally upon binding of
      calmodulin to target proteins, bends and unwinds near residue Arg74. We interpret
      this result as a preparative step in the more extensive structural transition
      observed in the "flexible linker" region 74-82 of the central helix upon complex
      formation. The major structural change is a reorientation of the two Ca2+-binding
      domains with respect to each other and a rearrangement of alpha-helices in the N
      terminus domain that makes the hydrophobic target peptide binding site more
      accessible. This structural rearrangement brings the domains to a more favorable
      position for target binding, poised to achieve the orientation observed in the
      complex of calmodulin with myosin light-chain kinase. Analysis of solvent
      structure reveals an inhomogeneity in the mobility of water in the vicinity of
      the protein, which is attributable to the hydrophobic effect exerted by
      calmodulin's binding sites for target peptides.

PMID- 9545029
TI  - Mathematical modeling and fluorescence imaging to study the Ca2+ turnover in
      skinned muscle fibers.
AB  - A mathematical model was developed for the simulation of the spatial and temporal
      time course of Ca2+ ion movement in caffeine-induced calcium transients of
      chemically skinned muscle fiber preparations. Our model assumes cylindrical
      symmetry and quantifies the radial profile of Ca2+ ion concentration by solving
      the diffusion equations for Ca2+ ions and various mobile buffers, and the rate
      equations for Ca2+ buffering (mobile and immobile buffers) and for the release
      and reuptake of Ca2+ ions by the sarcoplasmic reticulum (SR), with a finite
      difference algorithm. The results of the model are compared with caffeine-induced
      spatial Ca2+ transients obtained from saponin skinned murine fast-twitch fibers
      by fluorescence photometry and imaging measurements using the ratiometric dye
      Fura-2. The combination of mathematical modeling and digital image analysis
      provides a tool for the quantitative description of the total Ca2+ turnover and
      the different contributions of all interacting processes to the overall Ca2+
      transient in skinned muscle fibers. It should thereby strongly improve the usage
      of skinned fibers as quantitative assay systems for many parameters of the SR and
      the contractile apparatus helping also to bridge the gap to the intact muscle
      fiber.

PMID- 9545030
TI  - Fabrication of a new substrate for atomic force microscopic observation of DNA
      molecules from an ultrasmooth sapphire plate.
AB  - A new stable substrate applicable to the observation of DNA molecules by atomic
      force microscopy (AFM) was fabricated from a ultrasmooth sapphire (alpha-Al2O3
      single crystal) plate. The atomically ultrasmooth sapphire as obtained by high
      temperature annealing has hydrophobic surfaces and could not be used for the AFM
      observation of DNA. However, sapphire treated with Na3PO4 aqueous solution
      exhibited a hydrophilic character while maintaining a smooth surface structure.
      The surface of the wet-treated sapphire was found by x-ray photoelectron
      spectroscopy and AFM to be approximately 0.3 nm. The hydrophilic surface
      character of the ultrasmooth sapphire plate made it easy for DNA molecules to
      adhere to the plate. Circular molecules of the plasmid DNA could be imaged by AFM
      on the hydrophilic ultrasmooth sapphire plate.

PMID- 9545031
TI  - Computation of the internal forces in cilia: application to ciliary motion, the
      effects of viscosity, and cilia interactions.
AB  - This paper presents a simple and reasonable method for generating a
      phenomenological model of the internal mechanism of cilia. The model uses a
      relatively small number of parameters whose values can be obtained by fitting to
      ciliary beat shapes. Here, we use beat patterns observed in Paramecium. The
      forces that generate these beats are computed and fit to a simple functional form
      called the "engine." This engine is incorporated into a recently developed
      hydrodynamic model that accounts for interactions between neighboring cilia and
      between the cilia and the surface from which they emerge. The model results are
      compared to data on ciliary beat patterns of Paramecium obtained under conditions
      where the beats are two-dimensional. Many essential features of the motion,
      including several properties that are not built in explicitly, are shown to be
      captured. In particular, the model displays a realistic change in beat pattern
      and frequency in response to increased viscosity and to the presence of
      neighboring cilia in configurations such as rows of cilia and two-dimensional
      arrays of cilia. We found that when two adjacent model cilia start beating at
      different phases they become synchronized within several beat periods, as
      observed in experiments where two flagella are brought into close proximity.
      Furthermore, examination of various multiciliary configurations shows that an
      approximately antiplectic wave pattern evolves autonomously. This modeling
      evidence supports earlier conjectures that metachronism may occur, at least
      partially, as a self-organized phenomenon due to hydrodynamic interactions
      between neighboring cilia.

PMID- 9545032
TI  - Physical mechanisms for chemotactic pattern formation by bacteria.
AB  - This paper formulates a theory for chemotactic pattern formation by the bacteria
      Escherichia coli in the presence of excreted attractant. In a chemotactically
      neutral background, through chemoattractant signaling, the bacteria organize into
      swarm rings and aggregates. The analysis invokes only those physical processes
      that are both justifiable by known biochemistry and necessary and sufficient for
      swarm ring migration and aggregate formation. Swarm rings migrate in the absence
      of an external chemoattractant gradient. The ring motion is caused by the
      depletion of a substrate that is necessary to produce attractant. Several scaling
      laws are proposed and are demonstrated to be consistent with experimental data.
      Aggregate formation corresponds to finite time singularities in which the
      bacterial density diverges at a point. Instabilities of swarm rings leading to
      aggregate formation occur via a mechanism similar to aggregate formation itself:
      when the mass density of the swarm ring exceeds a threshold, the ring collapses
      cylindrically and then destabilizes into aggregates. This sequence of events is
      demonstrated both in the theoretical model and in the experiments.

PMID- 9545033
TI  - Numerical methods to determine calcium release flux from calcium transients in
      muscle cells.
AB  - Several methods are currently in use to estimate the rate of depolarization
      induced calcium release in muscle cells from measured calcium transients. One
      approach first characterizes calcium removal of the cell. This is done by
      determining parameters of a reaction scheme from a fit to the decay of elevated
      calcium after the depolarizing stimulus. In a second step, the release rate
      during depolarization is estimated based on the fitted model. Using simulated
      calcium transients with known underlying release rates, we tested the fidelity of
      this analysis in determining the time course of calcium release under different
      conditions. The analysis reproduced in a satisfactory way the characteristics of
      the input release rate, even when the assumption that release had ended before
      the start of the fitting interval was severely violated. Equally good
      reconstructions of the release rate time course could be obtained when the model
      used for the analysis differed in structure from the one used for simulating the
      data. We tested the application of a new strategy (multiple shooting) for fitting
      parameters in nonlinear differential equation systems. This procedure rendered
      the analysis less sensitive to ill-chosen initial guesses of the parameters and
      to noise. A locally adaptive kernel estimator for calculating numerical
      derivatives allowed good reconstructions of the original release rate time course
      from noisy calcium transients when other methods failed.

PMID- 9545034
TI  - Molecular dynamics simulation of cytochrome c3: studying the reduction processes
      using free energy calculations.
AB  - The tetraheme cytochrome c3 from Desulfovibrio vulgaris Hildenborough is studied
      using molecular dynamics simulation studies in explicit solvent. The high heme
      content of the protein, which has its core almost entirely made up of c-type
      heme, presents specific problems in the simulation. Instability in the structure
      is observed in long simulations above 1 ns, something that does not occur in a
      monoheme cytochrome, suggesting problems in heme parametrization. Given these
      stability problems, a partially restrained model, which avoids destruction of the
      structure, was created with the objective of performing free energy calculations
      of heme reduction, studies that require long simulations. With this model, the
      free energy of reduction of each individual heme was calculated. A correction in
      the long-range electrostatic interactions of charge groups belonging to the redox
      centers had to be made in order to make the system physically meaningful.
      Correlation is obtained between the calculated free energies and the experimental
      data for three of four hemes. However, the relative scale of the calculated
      energies is different from the scale of the experimental free energies. Reasons
      for this are discussed. In addition to the free energy calculations, this model
      allows the study of conformational changes upon reduction. Even if the precise
      details of the structural changes that take place in this system upon individual
      heme reduction are probably out of the reach of this study, it appears that these
      structural changes are small, similarly to what is observed for other redox
      proteins. This does not mean that their effect is minor, and one example is the
      conformational change observed in propionate D from heme I when heme II becomes
      reduced. A motion of this kind could be the basis of the experimentally observed
      cooperativity effects between heme reduction, namely positive cooperativity.

PMID- 9545035
TI  - Glucose diffusion in pancreatic islets of Langerhans.
AB  - We investigate the time required for glucose to diffuse through an isolated
      pancreatic islet of Langerhans and reach an equilibrium. This question is
      relevant in the context of in vitro electrophysiological studies of the response
      of an islet to step changes in the bath glucose concentration. Islet cells are
      electrically coupled by gap junctions, so nonuniformities in islet glucose
      concentration may be reflected in the activity of cells on the islet periphery,
      where electrical recordings are made. Using a mathematical model of hindered
      glucose diffusion, we investigate the effects of the islet porosity and the
      permeability of a surrounding layer of acinar cells. A major factor in the
      determination of the equilibrium time is the transport of glucose into islet beta
      cells, which removes glucose from the interstitial spaces where diffusion occurs.
      This transport is incorporated by using a model of the GLUT-2 glucose
      transporter. We find that several minutes are required for the islet to
      equilibrate to a 10 mM change in bath glucose, a typical protocol in islet
      experiments. It is therefore likely that in electrophysiological islet
      experiments the glucose distribution is nonuniform for several minutes after a
      step change in bath glucose. The delay in glucose penetration to the inner
      portions of the islet may be a major contributing factor to the 1-2-min delay in
      islet electrical activity typically observed after bath application of a
      stimulatory concentration of glucose.

PMID- 9545036
TI  - Strong precursor-pore interactions constrain models for mitochondrial protein
      import.
AB  - Mitochondrial precursor proteins are imported from the cytosol into the matrix
      compartment through a proteinaceous translocation pore. Import is driven by
      mitochondrial Hsp70 (mHsp70), a matrix-localized ATPase. There are currently two
      postulated mechanisms for this function of mHsp70: 1) The "Brownian ratchet"
      model proposes that the precursor chain diffuses within the pore, and that
      binding of mHsp70 to the lumenal portion of the chain biases this diffusion. 2)
      The "power stroke" model proposes that mHsp70 undergoes a conformational change
      that actively pulls the precursor chain through the pore. Here we formulate these
      two models quantitatively, and compare their performance in light of recent
      experimental evidence that precursor chains interact strongly with the walls of
      the translocation pore. Under these conditions the simulated Brownian ratchet is
      inefficient, whereas the power stroke mechanism seems to be a plausible
      description of the import process.

PMID- 9545037
TI  - The effect of protein relaxation on charge-charge interactions and dielectric
      constants of proteins.
AB  - The effect of the reorganization of the protein polar groups on charge-charge
      interaction and the corresponding effective dielectric constant (epsilon(eff)) is
      examined by the semimicroscopic version of the Protein Dipole Langevin Dipoles
      (PDLD/S) method within the framework of the Linear Response Approximation (LRA).
      This is done by evaluating the interactions between ionized residues in the
      reaction center of Rhodobacter sphaeroides, while taking into account the protein
      reorganization energy. It is found that an explicit consideration of the protein
      relaxation leads to a significant increase in epsilon(eff) and that
      semimicroscopic models that do not take this relaxation into account force one to
      use a large value for the so-called "protein dielectric constant," epsilon(p), of
      the Poisson-Boltzmann model or for the corresponding epsilon(in) in the PDLD/S
      model. An additional increase in epsilon(eff) is expected from the reorganization
      of ionized residues and from changes in the degree of water penetration. This
      finding provides further support for the idea that epsilon(in) (or epsilon(p))
      represents contributions that are not considered explicitly. The present study
      also provides a systematic illustration of the nature of epsilon(eff), supporting
      our previously reported view that charge-charge interactions correspond to a
      large value of this "dielectric constant," even in protein interiors. It is also
      pointed out that epsilon(eff) for the interaction between ionizable groups in
      proteins is very different from the effective dielectric constant, epsilon'(eff),
      that determines the free energy of ion pairs in proteins (epsilon'(eff) reflects
      the effect of preoriented protein dipoles). Finally, the problems associated with
      the search for a general epsilon(in) are discussed. It is clarified that the
      epsilon(in) that reproduces the effect of protein relaxation on charge-charge
      interaction is not equal to the epsilon(in) that reproduces the corresponding
      effect upon formation of individual charges. This reflects fundamental
      inconsistencies in attempts to cast microscopic concepts in a macroscopic model.
      Thus one should either use a large epsilon(in) for charge-charge interactions and
      a small epsilon(in) for charge-dipole interactions or consider the protein
      relaxation microscopically.

PMID- 9545038
TI  - Thermally induced proliferation of pores in a model fluid membrane.
AB  - The growth of thermally induced pores in a two-dimensional model fluid membrane
      is investigated by Monte Carlo simulation. Holes appear in the membrane via an
      activated process, and their subsequent growth is controlled by an edge energy
      per unit length or line tension. The barrier height and line tension, together
      with a lateral tension, are the independent parameters of the model. In the
      resulting phase diagram, a rupture transition separates an intact membrane from a
      disintegrated state. The approach to the ruptured state shows distinct regimes.
      Reducing the barrier height at large line tension produces multiple, quasi
      independent, small holes whose behavior is dominated by their edge energy,
      whereas at lower line tensions shape fluctuations of the holes facilitate their
      coalescence into a single large hole. At a small value of line tension and large
      barrier height, a single hole spontaneously permeabilizes the membrane in an
      entropically driven phase transition. Entropy dominates pore growth for line
      tensions not far below those measured for artificial vesicles. Permeabilization
      of lipid bilayers by certain peptides involves perturbing lipid-lipid cohesive
      energies, and our simulations show that at small line tensions the entropy of
      hole shape fluctuations destroys the model membrane's stability.

PMID- 9545039
TI  - Depolarization increases the single-channel conductance and the open probability
      of crayfish glutamate channels.
AB  - We have studied the voltage sensitivity of glutamate receptors in outside-out
      patches taken from crayfish muscles. We found that single-channel conductance,
      measured directly at the single-channel level, increases as depolarization rises.
      At holding potentials from -90 mV to approximately 20 mV, the conductance is 109
      pS. At holding potentials positive to 20 mV, the conductance is 213 pS. This
      increase in single-channel conductance was also observed in cell-attached
      patches. In addition, desensitization, rise time, and the dose-response curve
      were all affected by depolarization. To further clarify these multifaceted
      effects, we evaluated the kinetic properties of single-channel activity recorded
      from cell-attached patches in hyperpolarization (membrane potential around -75
      mV) and depolarization (membrane potential approximately 105 mV). We found that
      the glutamate dissociation rate constant (k_) was affected most significantly by
      membrane potential; it declined 6.5-fold under depolarization. The rate constant
      of channel closing (k(c)) was also significantly affected; it declined 1.8-fold.
      The rate constant of channel opening (k(o)) declined only 1.2-fold. The possible
      physiological significance of the depolarization-mediated changes in the above
      rate constants is discussed.

PMID- 9545041
TI  - Altered voltage dependence of fractional Ca2+ current in N-methyl-D-aspartate
      channel pore mutants with a decreased Ca2+ permeability.
AB  - The Ca2+ permeability properties of an N-methyl-D-aspartate (NMDA) channel pore
      mutant (NR1E603K-NR2A) were studied using whole-cell patch-clamp recordings in
      human embryonic kidney cells. Measurements of reversal potential shifts indicated
      that the relative permeability of Ca2+ over monovalent ions, P(Ca)/P(M), was 1.6,
      a value reduced by a factor of approximately 2 with respect to the wild-type
      channel. The ratio of Ca2+ current over total current (fractional Ca2+ current),
      however, was 19.7 +/- 1% at -50 mV and 2 mM external Ca2+ concentration, a value
      similar to that of the wild-type channel, but 2.3-fold larger than that predicted
      by simple permeation models for the corresponding P(Ca)/P(M) value. The deviation
      from predicted values gradually disappeared with membrane depolarization. Similar
      results were obtained for two cysteine mutations at asparagine residues of the
      NR1 and NR2A subunits. When interpreted in terms of a two-barrier one-site model
      for ion permeation, the results indicate that changes in the relative Ca2+
      permeability occur close to an internal energy barrier limiting ion permeation.

PMID- 9545040
TI  - Inactivation of Kv2.1 potassium channels.
AB  - We report here several unusual features of inactivation of the rat Kv2.1 delayed
      rectifier potassium channel, expressed in Xenopus oocytes. The voltage dependence
      of inactivation was U-shaped, with maximum inactivation near 0 mV. During a
      maintained depolarization, development of inactivation was slow and only weakly
      voltage dependent (tau = 4 s at 0 mV; tau = 7 s at +80 mV). However, recovery
      from inactivation was strongly voltage dependent (e-fold for 20 mV) and could be
      rapid (tau = 0.27 s at -140 mV). Kv2.1 showed cumulative inactivation, where
      inactivation built up during a train of brief depolarizations. A single
      maintained depolarization produced more steady-state inactivation than a train of
      pulses, but there could actually be more inactivation with the repeated pulses
      during the first few seconds. We term this phenomenon "excessive cumulative
      inactivation." These results can be explained by an allosteric model, in which
      inactivation is favored by activation of voltage sensors, but the open state of
      the channel is resistant to inactivation.

PMID- 9545042
TI  - Effect of luminal calcium on Ca2+ release channel activity of sarcoplasmic
      reticulum in situ.
AB  - Ca2+ influx into empty SR in the absence of Ca2+ pump activity was determined in
      skinned frog skeletal muscle fibers and compared with Ca2+ efflux from loaded SR
      (i.e., Ca2+ release) to deepen our understanding of the properties of the Ca2+
      release channel (CRC). Calcium content in SR increased approximately in a first
      order kinetics and finally reached the equilibrium level determined by
      cytoplasmic Ca2+ ([Ca2+]c). Because AMP caused an increase in the rate of Ca2+
      influx, and procaine, Mg2+, and high concentrations of Ca2+ caused a
      characteristic decrease, the major Ca2+ influx pathway was concluded to be the
      CRC, as is true of Ca2+ release. The apparent rate constant (k(app)) of Ca2+
      efflux did not significantly change when the loading level was decreased to one
      third. At a given [Ca2+]c, the same equilibrium level of calcium in SR was
      attained with a similar k(app) by both Ca2+ influx and Ca2+ efflux. The
      relationship between [Ca2+]c and calcium in SR indicated the Ca2+ binding sites
      in SR. These results, together with the anticipated effects of these Ca2+ buffer
      sites on kinetics, are consistent with the idea that luminal Ca2+ inhibits the
      CRC.

PMID- 9545043
TI  - A permanent ion binding site located between two gates of the Shaker K+ channel.
AB  - K+ channels can be occupied by multiple permeant ions that appear to bind at
      discrete locations in the conduction pathway. Neither the molecular nature of the
      binding sites nor their relation to the activation or inactivation gates that
      control ion flow are well understood. We used the permeant ion Ba2+ as a K+
      analog to probe for K+ ion binding sites and their relationship to the activation
      and inactivation gates. Our data are consistent with the existence of three
      single-file permeant-ion binding sites: one deep site, which binds Ba2+ with high
      affinity, and two more external sites whose occupancy influences Ba2+ movement to
      and from the deep site. All three sites are accessible to the external solution
      in channels with a closed activation gate, and the deep site lies between the
      activation gate and the C-type inactivation gate. We identify mutations in the P
      region that disrupt two of the binding sites, as well as an energy barrier
      between the sites that may be part of the selectivity filter.

PMID- 9545044
TI  - Assembly of ROMK1 (Kir 1.1a) inward rectifier K+ channel subunits involves
      multiple interaction sites.
AB  - The ROMK1 (Kir 1.1a) channel is formed by a tetrameric complex of subunits, each
      characterized by cytoplasmic N- and C-termini and a core region of two
      transmembrane helices flanking a pore-forming segment. To delineate the general
      regions mediating the assembly of ROMK1 subunits we constructed epitope-tagged N
      terminal, C-terminal, and transmembrane segment deletion mutants. Nonfunctional
      subunits with N-terminal, core region, and C-terminal deletions had dominant
      negative effects when coexpressed with wild-type ROMK1 subunits in Xenopus
      oocytes. In contrast, coexpression of these nonfunctional subunits with Kv 2.1
      (DRK1) did not suppress Kv 2.1 currents in control oocytes. Interactions between
      epitope-tagged mutant and wild-type ROMK1 subunits were studied in parallel by
      immunoprecipitating [35S]-labeled oocyte membrane proteins. Complexes containing
      both wild-type and mutant subunits that retained H5, M2, and C-terminal regions
      were coimmunoprecipitated to a greater extent than complexes consisting of wild
      type and mutant subunits with core region and/or C-terminal deletions. The
      present findings are consistent with the hypothesis that multiple interaction
      sites located in the core region and cytoplasmic termini of ROMK1 subunits
      mediate homomultimeric assembly.

PMID- 9545045
TI  - Both T- and L-type Ca2+ channels can contribute to excitation-contraction
      coupling in cardiac Purkinje cells.
AB  - Although L-type Ca2+ channels have been shown to play a central role in cardiac
      excitation-contraction (E-C) coupling, little is known about the role of T-type
      Ca2+ channels in this process. We used the amphotericin B perforated patch method
      to study the possible role of T-type Ca2+ current in E-C coupling in isolated
      canine Purkinje myocytes where both Ca2+ currents are large. T-type Ca2+ current
      was separated from L-type Ca2+ current using protocols employing the different
      voltage dependencies of the channel types and their different sensitivities to
      pharmacological blockade. We showed that Ca2+ admitted through either T- or L
      type Ca2+ channels is capable of initiating contraction and that the contractions
      depended on Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR). The
      contractions, however, had different properties. Those initiated by Ca2+ entry
      through T-type Ca2+ channels had a longer delay to the onset of shortening,
      slower rates of shortening and relaxation, lower peak shortening, and longer time
      to peak shortening. These differences were present even when L-type Ca2+ current
      amplitude, or charge entry, was less than that of T-type Ca2+ current, suggesting
      that Ca2+ entry through the T-type Ca2+ channel is a less effective signal
      transduction mechanism to the SR than is Ca2+ entry through the L-type Ca2+
      channel. We conclude that under our experimental conditions in cardiac Purkinje
      cells Ca2+ entry through the T-type Ca2+ channel can activate cell contraction.
      However, Ca2+ entry through the L-type Ca2+ channel is a more effective signal
      transduction mechanism. Our findings support the concept that different
      structural relationships exist between these channel types and the SR Ca2+
      release mechanism.

PMID- 9545046
TI  - Modulation of C-type inactivation by K+ at the potassium channel selectivity
      filter.
AB  - With prolonged or repetitive activation, voltage-gated K+ channels undergo a slow
      (C-type) inactivation mechanism, which decreases current flow through the
      channel. Previous observations suggest that C-type inactivation results from a
      localized constriction in the outer mouth of the channel pore and that the rate
      of inactivation is controlled by the-rate at which K+ leaves an unidentified
      binding site in the pore. We have functionally identified two K+ binding sites in
      the conduction pathway of a chimeric K+ channel that conducts Na+ in the absence
      of K+. One site has a high affinity for K+ and contributes to the selectivity
      filter mechanism for K+ over Na+. Another site, external to the high-affinity
      site, has a lower affinity for K+ and is not involved in channel selectivity.
      Binding of K+ to the high-affinity binding site slowed inactivation. Binding of
      cations to the external low-affinity site did not slow inactivation directly but
      could slow it indirectly, apparently by trapping K+ at the high-affinity site.
      These data support a model whereby C-type inactivation involves a constriction at
      the selectivity filter, and the constriction cannot proceed when the selectivity
      filter is occupied by K+.

PMID- 9545047
TI  - Mechanism of anode break stimulation in the heart.
AB  - Anodal stimulation is routinely observed in cardiac tissue, but only recently has
      a mechanism been proposed. The bidomain cardiac tissue model proposes that
      virtual cathodes induced at sites distant from the electrode initiate the
      depolarization. In contrast, none of the existing cardiac action potential models
      (Luo-Rudy phase I and II, or Oxsoft) predict anodal stimulation at the single
      cell level. To determine whether anodal stimulation has a cellular basis, we
      measured membrane potential and membrane current in mammalian ventricular
      myocytes by using whole-cell patch clamp. Anode break responses can be readily
      elicited in single ventricular cells. The basis of this anodal stimulation in
      single cells is recruitment of the hyperpolarization-activated inward current
      I(f). The threshold of activation for I(f) is -80 mV in rat cells and -120 mV in
      guinea pig or canine cells. Persistent I(f) "tail" current upon release of the
      hyperpolarization drives the transmembrane potential toward the threshold of
      sodium channels, initiating an action potential. Time-dependent block of the
      inward rectifier, I(K1), at hyperpolarized potentials decreases membrane
      conductance and thereby potentiates the ability of I(f) to depolarize the cell on
      the break of an anodal pulse. Inclusion of I(f), as well as the block and unblock
      kinetics of I(K1), in the existing Luo-Rudy action potential model faithfully
      reproduces anode break stimulation. Thus active cellular properties suffice to
      explain anode break stimulation in cardiac tissue.

PMID- 9545048
TI  - Pressure effects on the lateral distribution of cholesterol in lipid bilayers: a
      time-resolved spectroscopy study.
AB  - The effects of hydrostatic pressure and temperature on the phase behavior and
      physical properties of the binary mixture
      palmitoyloleoylphosphatidylcholine/cholesterol, over the 0-40 molar % range of
      cholesterol compositions, were determined from the changes in the fluorescence
      lifetime distribution and anisotropy decay parameters of the natural lipid trans
      parinaric acid (t-PnA). Pressurized samples were excited with a Ti-sapphire
      subpicosecond laser, and fluorescence decays were analyzed by the quantified
      maximum entropy method. Above the transition temperature (T(T) = -5 degrees C),
      at atmospheric pressure, two liquid-crystalline phases, alpha and beta, are
      formed in this system. At each temperature and cholesterol concentration below
      the transition pressure, the fluorescence lifetime distribution pattern of t-PnA
      was clearly modulated by the pressure changes. Pressure increased the fraction of
      the liquid-ordered beta-phase and its order parameter, but it decreased the
      amount of cholesterol in this phase.
      Palmitoyloleoylphosphatidylcholine/cholesterol phase diagrams were also
      determined as a function of temperature and hydrostatic pressure.

PMID- 9545049
TI  - Studies of the binding and structure of adrenocorticotropin peptides in membrane
      mimics by NMR spectroscopy and pulsed-field gradient diffusion.
AB  - The partition and structure of three adrenocorticotropic hormone peptides ACTH(1
      10), ACTH(1-24), and ACTH(11-24) in water and in sodium dodecylsulfate (SDS) and
      dodecylphosphocholine (DPC) micelles were studied by 2D NMR and NMR gradient
      diffusion measurements. The diffusion rates, the NH chemical shifts, and the
      nuclear Overhauser effect patterns provided a coherent picture of binding of
      these peptides. All three peptides are significantly partitioned in the
      negatively charged SDS micelles and possess definite secondary structure, as
      opposed to random structures in water. For ACTH (1-24), the hydrophobic 1-10
      segment is partitioned in DPC micelles, but the charged 11-24 segment prefers to
      remain in the aqueous region. ACTH(11-24) does not bind significantly to the DPC
      micelles. The binding of the ACTH peptides in these two widely used "membrane
      mimics" are substantially different from that in 1-palmitoyl-2-oleoyl-sn-glycero
      3-phosphocholine (POPC) bilayers obtained by attenuated total reflection infrared
      spectroscopy and from our preliminary diffusion studies of the same peptides in
      POPC vesicles. This study showed that, in a given micellar medium, all
      corresponding segments of these peptides are located in the same membrane
      environment in the system, regardless of whether these segments exist by
      themselves or are attached to other segments. This result may contradict the
      membrane-compartments concept of Schwyzer, which suggests that ACTH(1-10) and
      ACTH(1-24) are located in different membrane compartments because they have
      different address segments, and consequently, bind to different receptors. The
      present results also suggest that the assumption that micelles are good membrane
      mimics should be carefully examined.

PMID- 9545050
TI  - Correlation between electric field pulse induced long-lived permeabilization and
      fusogenicity in cell membranes.
AB  - Electric field pulses have been reported to induce long-lived permeabilization
      and fusogenicity on cell membranes. The two membrane property alterations are
      under the control of the field strength, the pulse duration, and the number of
      pulses. Experiments on mammalian cells pulsed by square wave form pulses and then
      brought into contact randomly through centrifugation revealed an even stronger
      analogy between the two processes. Permeabilization was known to affect well
      defined regions of the cell surface. Fusion can be obtained only when
      permeabilized surfaces on the two partners were brought into contact.
      Permeabilization was under the control of the pulse duration and of the number of
      pulses. A similar relationship was observed as far as fusion is concerned. But a
      critical level of local permeabilization must be present for fusion to take place
      when contacts are created. The same conclusions are obtained from previous
      experiments on ghosts subjected to exponentially decaying field pulses and then
      brought into contact by dielectrophoresis. These observations are in agreement
      with a model of membrane fusion in which the merging of local random defects
      occurs when the two membranes are brought into contact. The local defects are
      considered part of the structural membrane reorganization induced by the external
      field. Their density is dependent on the pulse duration and number of pulses.
      They support the long-lived permeabilization. Their number must be very large to
      support the occurrence of membrane fusion.

PMID- 9545051
TI  - Effects of a cationic and hydrophobic peptide, KL4, on model lung surfactant
      lipid monolayers.
AB  - We report on the surface behavior of a hydrophobic, cationic peptide, [lysine
      (leucine)4]4-lysine (KL4), spread at the air/water interface at 25 degrees C and
      pH 7.2, and its effect at very low molar ratios on the surface properties of the
      zwitterionic phospholipid 1,2-dipalmitoylphosphatidylcholine (DPPC), and the
      anionic forms of 1-palmitoyl-2-oleoylphosphatidylglycerol (POPG) and palmitic
      acid (PA), in various combinations. Surface properties were evaluated by
      measuring equilibrium spreading pressures (pi(e)) and surface pressure-area
      isotherms (pi-A) with the Wilhelmy plate technique. Surface phase separation was
      observed with fluorescence microscopy. KL4 itself forms a single-phase monolayer,
      stable up to a surface pressure pi of 30 mN/m, and forms an immiscible monolayer
      mixture with DPPC. No strong interaction was detected between POPG and KL4 in the
      low pi region, whereas a stable monolayer of the PA/KL4 binary mixture forms,
      which is attributed to ionic interactions between oppositely charged PA and KL4.
      KL4 has significant effects on the DPPC/POPG mixture, in that it promotes surface
      phase separation while also increasing pi(e) and pi(max), and these effects are
      greatly enhanced in the presence of PA. In the model we have proposed, KL4
      facilitates the separation of DPPC-rich and POPG/PA-rich phases to achieve
      surface refinement. It is these two phases that can fulfill the important lung
      surfactant functions of high surface pressure stability and efficient spreading.

PMID- 9545052
TI  - Hydration of the dienic lipid dioctadecadienoylphosphatidylcholine in the
      lamellar phase--an infrared linear dichroism and x-ray study on headgroup
      orientation, water ordering, and bilayer dimensions.
AB  - In the phospholipid 1,2-bis(2,4-octadecadienoyl)-sn-glycero-3-phosphorylcholine
      (DODPC) in each of the fatty acid chains, a rigid diene group is inserted in a
      position near the polar/apolar boundary that is exceptionally sensitive for
      membrane stability. DODPC transforms upon gradual dehydration from the liquid
      crystalline to a metastable gel state, which rearranges into two subgel phases at
      low and intermediate degrees of hydration. The molecular dimensions of the
      respective bilayers were determined by means of x-ray diffraction. Infrared
      linear dichroism of selected vibrations of the phosphate and trimethylammonium
      groups and of the nu13(OH) band of water adsorbed onto the lipid was used to
      study the molecular order in the polar part of the bilayers in macroscopically
      oriented samples. The dense packing of the tilted acyl chains in the subgel
      causes the in-plane orientation of the phosphatidylcholine headgroups with direct
      interactions between the phosphate and trimethylammonium groups, and a strong
      orientation of adsorbed water molecules. In the more disordered gel, the
      thickness of the polar part of the bilayer increases and the lateral interactions
      between the lipid headgroups weaken. The higher order in the headgroup region of
      the subgels correlates with shorter decay lengths of the repulsive forces acting
      between opposite membrane surfaces. This result can be understood if the work to
      dehydrate the lipid is determined to a certain degree by the work to break up the
      lipid-water interactions without compensation by adequate lipid-lipid contacts.
      Almost similar area compressibility moduli are found in the liquid-crystalline
      and solid phases. Obviously, the lipid avoids lateral stress by the structural
      rearrangement.

PMID- 9545053
TI  - Membrane structure characterization using variable-period x-ray standing waves.
AB  - The variable-period x-ray standing wave (XSW) technique is emerging as a powerful
      tool for studying membrane structure. However, two significant problems arise
      when the method is used to characterize membranes of thickness dL < 100 A. First,
      the surface roughness, sigma(r), of the supporting reflecting mirror convolutes
      with the intrinsic half-width of the marker atom distribution in the membrane,
      sigma(in), and contributes to an apparent half-width, sigma, which is measured in
      the XSW experiment. Here we show how the latter terms are related quantitatively
      [sigma(in) = (sigma2 - sigma(r)2)(1/2)], such that rough mirrors give rise to
      larger marker atom distribution widths, sigma, and how the required quantity
      sigma(in) can be determined in the XSW measurement. Second, when the mean
      position of the marker atom layer, (z), is close to one or both boundaries of the
      membrane, its distribution function is truncated at the boundary. In such cases,
      we show why marker atom distribution should be expressed in terms of its first
      and second moments. We also demonstrate by numerical simulations of realistic
      samples how the physical parameters, sigma(r), sigma, (z), and dL, affect x-ray
      reflectivity and fluorescence yield profiles as an aid in their interpretation.

PMID- 9545054
TI  - Electrochemical measurement of lateral diffusion coefficients of ubiquinones and
      plastoquinones of various isoprenoid chain lengths incorporated in model
      bilayers.
AB  - The long-range diffusion coefficients of isoprenoid quinones in a model of lipid
      bilayer were determined by a method avoiding fluorescent probe labeling of the
      molecules. The quinone electron carriers were incorporated in supported
      dimyristoylphosphatidylcholine layers at physiological molar fractions (<3 mol%).
      The elaborate bilayer template contained a built-in gold electrode at which the
      redox molecules solubilized in the bilayer were reduced or oxidized. The lateral
      diffusion coefficient of a natural quinone like UQ10 or PQ9 was 2.0 +/- 0.4 x 10(
      8) cm2 s(-1) at 30 degrees C, two to three times smaller than the diffusion
      coefficient of a lipid analog in the same artificial bilayer. The lateral
      mobilities of the oxidized or reduced forms could be determined separately and
      were found to be identical in the 4-13 pH range. For a series of isoprenoid
      quinones, UQ2 or PQ2 to UQ10, the diffusion coefficient exhibited a marked
      dependence on the length of the isoprenoid chain. The data fit very well the
      quantitative behavior predicted by a continuum fluid model in which the
      isoprenoid chains are taken as rigid particles moving in the less viscous part of
      the bilayer and rubbing against the more viscous layers of lipid heads. The
      present study supports the concept of a homogeneous pool of quinone located in
      the less viscous region of the bilayer.

PMID- 9545055
TI  - The effects of solutes on the freezing properties of and hydration forces in
      lipid lamellar phases.
AB  - Quantitative deuterium nuclear magnetic resonance is used to study the freezing
      behavior of the water in phosphatidylcholine lamellar phases, and the effect upon
      it of dimethylsulfoxide (DMSO), sorbitol, sucrose, and trehalose. When sufficient
      solute is present, an isotropic phase of concentrated aqueous solution may
      coexist with the lamellar phase at freezing temperatures. We determine the
      composition of both unfrozen phases as a function of temperature by using the
      intensity of the calibrated free induction decay signal (FID). The presence of
      DMSO or sorbitol increases the hydration of the lamellar phase at all freezing
      temperatures studied, and the size of the increase in hydration is comparable to
      that expected from their purely osmotic effect. Sucrose and trehalose increase
      the hydration of the lamellar phase, but, at concentrations of several molal, the
      increase is less than that which their purely osmotic effect would be expected to
      produce. A possible explanation is that very high volume fractions of sucrose and
      trehalose disrupt the water structure and thus reduce the repulsive hydration
      interaction between membranes. Because of their osmotic effect, all of the
      solutes studied reduced the intramembrane mechanical stresses produced in
      lamellar phases by freezing. Sucrose and trehalose at high concentrations produce
      a greater reduction than do the other solutes.

PMID- 9545056
TI  - Energetics of inclusion-induced bilayer deformations.
AB  - The material properties of lipid bilayers can affect membrane protein function
      whenever conformational changes in the membrane-spanning proteins perturb the
      structure of the surrounding bilayer. This coupling between the protein and the
      bilayer arises from hydrophobic interactions between the protein and the bilayer.
      We analyze the free energy cost associated with a hydrophobic mismatch, i.e., a
      difference between the length of the protein's hydrophobic exterior surface and
      the average thickness of the bilayer's hydrophobic core, using a (liquid-crystal)
      elastic model of bilayer deformations. The free energy of the deformation is
      described as the sum of three contributions: compression-expansion, splay
      distortion, and surface tension. When evaluating the interdependence among the
      energy components, one modulus renormalizes the other: e.g., a change in the
      compression-expansion modulus affects not only the compression-expansion energy
      but also the splay-distortion energy. The surface tension contribution always is
      negligible in thin solvent-free bilayers. When evaluating the energy per unit
      distance (away from the inclusion), the splay-distortion component dominates
      close to the bilayer/inclusion boundary, whereas the compression-expansion
      component is more prominent further away from the boundary. Despite this
      complexity, the bilayer deformation energy in many cases can be described by a
      linear spring formalism. The results show that, for a protein embedded in a
      membrane with an initial hydrophobic mismatch of only 1 A, an increase in
      hydrophobic mismatch to 1.3 A can increase the Boltzmann factor (the equilibrium
      distribution for protein conformation) 10-fold due to the elastic properties of
      the bilayer.

PMID- 9545057
TI  - Prodan as a membrane surface fluorescence probe: partitioning between water and
      phospholipid phases.
AB  - Fluorescence spectral features of 6-propionyl-2-dimethylaminonaphthalene (Prodan)
      in phospholipid vesicles of different phase states are investigated. Like the
      spectra of 6-lauroyl-2-dimethylaminonaphthalene (Laurdan), the steady-state
      excitation and emission spectra of Prodan are sensitive to the polarity of the
      environment, showing a relevant shift due to the dipolar relaxation phenomenon.
      Because of the different lengths of their acyl residues, the partitioning of the
      two probes between water and the membrane bilayer differs profoundly. To account
      for the contribution of Prodan fluorescence arising from water, we introduce a
      three-wavelength generalized polarization method that makes it possible to
      separate the spectral properties of Prodan in the lipid phase and in water, and
      to determine the probe partitioning between phospholipid and water and between
      the gel and the liquid-crystalline phases of phospholipids. In contrast to
      Laurdan, Prodan preferentially partitions in the liquid-crystalline phase with
      respect to the gel and is sensitive to the polar head pretransition, and its
      partition coefficient between the membrane and water depends on the phase state,
      i.e., on the packing of the bilayer. Prodan is sensitive to polarity variations
      occurring closer to the bilayer surface than those detected by Laurdan.

PMID- 9545058
TI  - Force regulation by Ca2+ in skinned single cardiac myocytes of frog.
AB  - Atrial and ventricular myocytes 200 to 300 microm long containing one to five
      myofibrils are isolated from frog hearts. After a cell is caught and held between
      two suction micropipettes the surface membrane is destroyed by briefly jetting
      relaxing solution containing 0.05% Triton X-100 on it from a third micropipette.
      Jetting buffered Ca2+ from other pipettes produces sustained contractions that
      relax completely on cessation. The pCa/force relationship is determined at 20
      degrees C by perfusing a closely spaced sequence of pCa concentrations (pCa = 
      log[Ca2+]) past the skinned myocyte. At each step in the pCa series quick release
      of the myocyte length defines the tension baseline and quick restretch allows the
      kinetics of the return to steady tension to be observed. The pCa/force data fit
      to the Hill equation for atrial and ventricular myocytes yield, respectively, a
      pK (curve midpoint) of 5.86 +/- 0.03 (mean +/- SE.; n = 7) and 5.87 +/- 0.02 (n =
      18) and an nH (slope) of 4.3 +/- 0.34 and 5.1 +/- 0.35. These slopes are about
      double those reported previously, suggesting that the cooperativity of Ca2+
      activation in frog cardiac myofibrils is as strong as in fast skeletal muscle.
      The shape of the pCa/force relationship differs from that usually reported for
      skeletal muscle in that it closely follows the ideal fitted Hill plot with a
      single slope while that of skeletal muscle appears steeper in the lower than in
      the upper half. The rate of tension redevelopment following release restretch
      protocol increases with Ca2+ >10-fold and continues to rise after Ca2+ activated
      tension saturates. This finding provides support for a strong kinetic mechanism
      of force regulation by Ca2+ in frog cardiac muscle, at variance with previous
      reports on mammalian heart muscle. The maximum rate of tension redevelopment
      following restretch is approximately twofold faster for atrial than for
      ventricular myocytes, in accord with the idea that the intrinsic speed of the
      contractile proteins is faster in atrial than in ventricular myocardium.

PMID- 9545060
TI  - Behavior of supercoiled DNA.
AB  - We study DNA supercoiling in a quantitative fashion by micromanipulating single
      linear DNA molecules with a magnetic field gradient. By anchoring one end of the
      DNA to multiple sites on a magnetic bead and the other end to multiple sites on a
      glass surface, we were able to exert torsional control on the DNA. A rotating
      magnetic field was used to induce rotation of the magnetic bead, and reversibly
      over- and underwind the molecule. The magnetic field was also used to increase or
      decrease the stretching force exerted by the magnetic bead on the DNA. The
      molecule's degree of supercoiling could therefore be quantitatively controlled
      and monitored, and tethered-particle motion analysis allowed us to measure the
      stretching force acting on the DNA. Experimental results indicate that this is a
      very powerful technique for measuring forces at the picoscale. We studied the
      effect of stretching forces ranging from 0.01 pN to 100 pN on supercoiled DNA (
      0.1 < sigma < 0.2) in a variety of ionic conditions. Other effects, such as
      stretching-relaxing hysteresis and the braiding of two DNA molecules, are
      discussed.

PMID- 9545059
TI  - Calcium regulation of tension redevelopment kinetics with 2-deoxy-ATP or low
      [ATP] in rabbit skeletal muscle.
AB  - The correlation of acto-myosin ATPase rate with tension redevelopment kinetics
      (k(tr)) was determined during Ca(+2)-activated contractions of demembranated
      rabbit psoas muscle fibers; the ATPase rate was either increased or decreased
      relative to control by substitution of ATP (5.0 mM) with 2-deoxy-ATP (dATP) (5.0
      mM) or by lowering [ATP] to 0.5 mM, respectively. The activation dependence of
      k(tr) and unloaded shortening velocity (Vu) was measured with each substrate.
      With 5.0 mM ATP, Vu depended linearly on tension (P), whereas k(tr) exhibited a
      nonlinear dependence on P, being relatively independent of P at submaximum levels
      and rising steeply at P > 0.6-0.7 of maximum tension (Po). With dATP, Vu was 25%
      greater than control at Po and was elevated at all P > 0.15Po, whereas Po was
      unchanged. Furthermore, the Ca(+2) sensitivity of both k(tr) and P increased,
      such that the dependence of k(tr) on P was not significantly different from
      control, despite an elevation of Vu and maximal k(tr). In contrast, lowering
      [ATP] caused a slight (8%) elevation of Po, no change in the Ca(+2) sensitivity
      of P, and a decrease in Vu at all P. Moreover, k(tr) was decreased relative to
      control at P > 0.75Po, but was elevated at P < 0.75Po. These data demonstrate
      that the cross-bridge cycling rate dominates k(tr) at maximum but not submaximum
      levels of Ca(2+) activation.

PMID- 9545061
TI  - PsaC subunit of photosystem I is oriented with iron-sulfur cluster F(B) as the
      immediate electron donor to ferredoxin and flavodoxin.
AB  - The PsaC subunit of photosystem I (PS I) binds two [4Fe-4S] clusters, F(A) and
      F(B), functioning as electron carriers between F(X) and soluble ferredoxin. To
      resolve the issue whether F(A) or F(B) is proximal to F(X), we used single
      turnover flashes to promote step-by-step electron transfer between electron
      carriers in control (both F(A) and F(B) present) and HgCl2-treated (F(B)-less) PS
      I complexes from Synechococcus sp. PCC 6301 and analyzed the kinetics of P700+
      reduction by monitoring the absorbance changes at 832 nm in the presence of a
      fast electron donor (phenazine methosulfate (PMS)). In control PS I complexes
      exogenously added ferredoxin, or flavodoxin could be photoreduced on each flash,
      thus allowing P700+ to be reduced from PMS. In F(B)-less complexes, both in the
      presence and in the absence of ferredoxin or flavodoxin, P700+ was reduced from
      PMS only on the first flash and was reduced from F(X)- on the following flashes,
      indicating lack of electron transfer to ferredoxin or flavodoxin. In the F(B)
      less complexes, a normal level of P700 photooxidation was detected accompanied by
      a high yield of charge recombination between P700+ and F(A)- in the presence of a
      slow donor, 2,6-dichlorophenol-indophenol. This recombination remained the only
      pathway of F(A)- reoxidation in the presence of added ferredoxin, consistent with
      the lack of forward electron transfer. F(A)- could be reoxidized by methyl
      viologen in F(B)-less PS I complexes, although at a concentration two orders of
      magnitude higher than is required in wild-type PS I complexes, thus implying the
      presence of a diffusion barrier. The inhibition of electron transfer to
      ferredoxin and flavodoxin was completely reversed after reconstituting the F(B)
      cluster. Using rate versus distance estimates for electron transfer rates from
      F(X) to ferredoxin for two possible orientations of PsaC, we conclude that the
      kinetic data are best compatible with PsaC being oriented with F(A) as the
      cluster proximal to F(X) and F(B) as the distal cluster that donates electrons to
      ferredoxin.

PMID- 9545062
TI  - Association and dissociation kinetics of anti-hen egg lysozyme monoclonal
      antibodies HyHEL-5 and HyHEL-10.
AB  - The immunoglobulin G1 (IgG1) kappa antibodies HyHEL-5 and HyHEL-10 interact with
      nonoverlapping epitopes on hen egg lysozyme (HEL); the HyHEL-5/HEL interface has
      two energetically and structurally important salt links, whereas the HyHEL-10/HEL
      interface involves predominantly hydrogen bonds and van der Waals interactions.
      The kinetics of association and dissociation of antibodies HyHEL-5 and HyHEL-10
      with HEL under a variety of conditions were investigated in this study. The
      association of each antibody with HEL follows second-order kinetics. The
      association process is significantly diffusion-limited, as indicated by the
      viscosity dependence of the interaction of both antibodies with HEL, although
      detailed energetics suggest that the association process may be more complex. The
      association rate constant for the HyHEL-5/HEL system is within a factor of 2 of
      the modified Smoluchowski estimate for proteins of this size, whereas HyHEL-10
      interacts with HEL with an association rate an order of magnitude lower. The
      association reactions are insensitive to ionic strength, showing only a twofold
      decrease in the association rate constant when the ionic strength was increased
      from 27 mM to 500 mM. Interestingly, the association rate constant for the
      interaction of HyHEL-5 with HEL varies with pH in the range 6.0-10.0, whereas
      HyHEL-10/HEL association is not affected by pH in the same range. The
      dissociation of the HyHEL-5/HEL and HyHEL-10/HEL complexes follow first-order
      kinetics with half-lives at 25 degrees C of approximately 3,150 s and
      approximately 21,660 s, respectively.

PMID- 9545063
TI  - Flavin fluorescence dynamics and photoinduced electron transfer in Escherichia
      coli glutathione reductase.
AB  - Time-resolved polarized flavin fluorescence was used to study the active site
      dynamics of Escherichia coli glutathione reductase (GR). Special consideration
      was given to the role of Tyr177, which blocks the access to the NADPH binding
      site in the crystal structure of the enzyme. By comparing wild-type GR with the
      mutant enzymes Y177F and Y177G, a fluorescence lifetime of 7 ps that accounts for
      approximately 90% of the fluorescence decay could be attributed to quenching by
      Y177. Based on the temperature invariance for this lifetime, and the very high
      quenching rate, electron transfer from Y177 to the light-excited isoalloxazine
      part of flavin adenine dinucleotide (FAD) is proposed as the mechanism of flavin
      fluorescence quenching. Contrary to the mutant enzymes, wild-type GR shows a
      rapid fluorescence depolarization. This depolarization process is likely to
      originate from a transient charge transfer interaction between Y177 and the light
      excited FAD, and not from internal mobility of the flavin, as has previously been
      proposed. Based on the fluorescence lifetime distributions, the mutants Y177F and
      Y177G have a more flexible protein structure than wild-type GR: in the range of
      223 K to 277 K in 80% glycerol, both tyrosine mutants mimic the closely related
      enzyme dihydrolipoyl dehydrogenase. The fluorescence intensity decays of the GR
      enzymes can only be explained by the existence of multiple quenching sites in the
      protein. Although structural fluctuations are likely to contribute to the
      nonexponential decay and the probability of quenching by a specific site, the
      concept of conformational substates need not be invoked to explain the
      heterogeneous fluorescence dynamics.

PMID- 9545064
TI  - Structural characterization of the hydrophobin SC3, as a monomer and after self
      assembly at hydrophobic/hydrophilic interfaces.
AB  - Hydrophobins are small fungal proteins that self-assemble at
      hydrophilic/hydrophobic interfaces into amphipathic membranes that, in the case
      of Class I hydrophobins, can be disassembled only by treatment with agents like
      pure trifluoroacetic acid. Here we characterize, by spectroscopic techniques, the
      structural changes that occur upon assembly at an air/water interface and upon
      assembly on a hydrophobic solid surface, and the influence of deglycosylation on
      these events. We determined that the hydrophobin SC3 from Schizophyllum commune
      contains 16-22 O-linked mannose residues, probably attached to the N-terminal
      part of the peptide chain. Scanning force microscopy revealed that SC3 adsorbs
      specifically to a hydrophobic surface and cannot be removed by heating at 100
      degrees C in 2% sodium dodecyl sulfate. Attenuated total reflection Fourier
      transform infrared spectroscopy and circular dichroism spectroscopy revealed that
      the monomeric, water-soluble form of the protein is rich in beta-sheet structure
      and that the amount of beta-sheet is increased after self-assembly on a water-air
      interface. Alpha-helix is induced specifically upon assembly of the protein on a
      hydrophobic solid. We propose a model for the formation of rodlets, which may be
      induced by dehydration and a conformational change of the glycosylated part of
      the protein, resulting in the formation of an amphipathic alpha-helix that forms
      an anchor for binding to a substrate. The assembly in the beta-sheet form seems
      to be involved in lowering of the surface tension, a potential function of
      hydrophobins.

PMID- 9545065
TI  - Energy transfers in the B808-866 antenna from the green bacterium Chloroflexus
      aurantiacus.
AB  - Energy transfers within the B808-866 BChl a antenna in chlorosome-membrane
      complexes from the green photosynthetic bacterium Chloroflexus aurantiacus were
      studied in two-color pump-probe experiments at room temperature. The steady-state
      spectroscopy and protein sequence of the B808-866 complex are reminiscent of well
      studied LH2 antennas from purple bacteria. B808-->B866 energy transfers occur
      with approximately 2 ps kinetics; this is slower by a factor of approximately 2
      than B800-->B850 energy transfers in LH2 complexes from Rhodopseudomonas
      acidophila or Rhodobacter sphaeroides. Anisotropy studies show no evidence for
      intra-B808 energy transfers before the B808-->B866 step; intra-B866 processes are
      reflected in 350-550 fs anisotropy decays. Two-color anisotropies under 808 nm
      excitation suggest the presence of a B808-->B866 channel arising either from
      direct laser excitation of upper B866 exciton components that overlap the B808
      absorption band or from excitation of B866 vibronic bands in nontotally symmetric
      modes.

PMID- 9545066
TI  - Optical chemical imaging of tobacco mosaic virus in solution at 60-nm resolution.
AB  - Scanning near-field optical microscopy can provide images with a resolution less
      than the wavelength of light, and therefore ought in principle to be of great
      value in studies of biological structures. In this work we show how for the first
      time images have been obtained of tobacco mosaic virus particles at 60-nm
      resolution, combined with chemical imaging using monoclonal antibodies under in
      vitro conditions.

PMID- 9545067
TI  - Micropipet-based pico force transducer: in depth analysis and experimental
      verification.
AB  - Measurements of forces in the piconewton range are very important for the study
      of molecular adhesion and mechanics. Recently, a micropipet-based force
      transducer for this type of experiment was presented (E. Evans, K. Ritchie, and
      R. Merkel, 1995, Biophys. J., 68:2580-2587). In the present article we give a
      detailed mechanical analysis of this transducer, including nonlinear effects. An
      analytical expression for the transducer stiffness at small elongations is given.
      Using magnetic tweezers (F. Ziemann, J. Radler, and E. Sackmann, 1994, Biophys.
      J., 66:2210-2216), we were able to determine the force displacement relation of
      this transducer experimentally. Forces from approximately 10 pN to 500 pN were
      applied. Theoretical predictions and experimental results coincide remarkably
      well.

PMID- 9545068
TI  - Depolarized resonance light scattering by porphyrin and chlorophyll a aggregates.
AB  - A quantum mechanical model is developed for the observed resonance enhancement of
      light scattering by aggregates of electronically interacting chromophores.
      Aggregate size, monomer oscillator strength, extent of electronic coupling, and
      aggregate geometry are all important determinants of intensity in resonance light
      scattering (RLS) spectra. The theory also predicts the value of the
      depolarization ratio (rho(v)(90)) of RLS for a given aggregate geometry. These
      results are used to interpret the RLS depolarization ratios of four aggregates:
      tetrakis(4-sulfonatophenyl)porphine aggregated at low pH (rho(v)(90) = 0.17 at
      488 nm), trans-bis(N-methylpyridinium-4-yl)-diphenylporphinato copper(II)
      aggregated in 0.2 M NaCl solution (rho(v)(90) = 0.13 at 450 nm) and on calf
      thymus DNA (rho(v)(90) = 0.20 at 454 nm), and chlorophyll a aggregates in
      formamide/water (rho(v)(90) = 0.23 and 0.32 at 469 and 699 nm, respectively). The
      analysis is consistent with a J-aggregate geometry for all four systems.
      Furthermore, the specific values of rho(v)(90) allow us to estimate the
      orientation of the monomer transition dipoles with respect to the long axis of
      the aggregate. We conclude that depolarized resonance light scattering
      spectroscopy is a powerful probe of the geometric and electronic structures of
      extended aggregates of strong chromophores.

PMID- 9545069
TI  - Comparison of secretory responses as measured by membrane capacitance and by
      amperometry.
AB  - We have compared capacitance and amperometric measurements in bovine chromaffin
      cells when secretion was elicited by flash photolysis of caged-calcium or step
      depolarizations. Total amperometric charge depended linearly on the amount of
      capacitance increase in both types of experiments. Furthermore, the properties of
      resolvable amperometric spikes after flashes were comparable to those observed
      after depolarizations, and their timing was compatible with the rate of
      capacitance increase. For a more detailed comparison, we used Monte Carlo
      simulations of multiple amperometric events occurring randomly over the surface
      of a sphere and summing together, to generate a reference amperometric signal for
      a given measured capacitance increase. Even after correction for endocytotic
      processes, the time courses of the integrated experimental records lagged behind
      the integrated Monte Carlo records by approximately 50 ms in flash and
      depolarization experiments. This delay was larger by approximately 40 ms than
      what can be expected from the "pre-foot delay" or the foot duration. Possible
      sources for the remaining delay could be diffusional barriers like the patch
      pipette and the chamber bottom, which are not taken into account in the model. We
      also applied a novel type of fluctuation analysis to estimate the relative
      quantum size of an amperometric event. On average the estimates from experimental
      amperometric traces, in both flash and depolarization experiments, were 3-5 times
      smaller than estimates from simulated ones. This discrepancy can be due to
      contributions to the amperometric current from small vesicles, preferred release
      from cellular regions orientated toward the chamber bottom, or abundance of "foot
      only" events. In conclusion, amperometric signals in flash and depolarization
      experiments displayed similar delayed average time courses and a lower estimate
      for the relative quantum size compared to the modeled amperometric signals.
      However, individual amperometric spikes were in agreement with expectations
      derived from capacitance signals.

PMID- 9545070
TI  - Low frequency electrorotation of fixed red blood cells.
AB  - Electrorotation of fixed red blood cells has been investigated in the frequency
      range between 16 Hz and 30 MHz. The rotation was studied as a function of
      electrolyte conductivity and surface charge density. Between 16 Hz and 1 kHz,
      fixed red blood cells undergo cofield rotation. The maximum of cofield rotation
      occurs between 30 and 70 Hz. The position of the maximum depends weakly on the
      bulk electrolyte conductivity and surface charge density. Below 3.5 mS/m, the
      cofield rotation peak is broadened and shifted to higher frequencies accompanied
      by a decrease of the rotation speed. Surface charge reduction leads to a decrease
      of the rotation speed in the low frequency range. These observations are
      consistent with the recently developed electroosmotic theory of low frequency
      electrorotation.

PMID- 9545072
TI  - Imaging the permeability pore transition in single mitochondria.
AB  - In mitochondria the opening of a large proteinaceous pore, the "mitochondrial
      permeability transition pore" (MTP), is known to occur under conditions of
      oxidative stress and matrix calcium overload. MTP opening and the resulting
      cellular energy deprivation have been implicated in processes such as hypoxic
      cell damage, apoptosis, and neuronal excitotoxicity. Membrane potential (delta
      psi(m)) in single isolated heart mitochondria was measured by confocal microscopy
      with a voltage-sensitive fluorescent dye. Measurements in mitochondrial
      populations revealed a gradual loss of delta psi(m) due to the light-induced
      generation of free radicals. In contrast, the depolarization in individual
      mitochondria was fast, sometimes causing marked oscillations of delta psi(m).
      Rapid depolarizations were accompanied by an increased permeability of the inner
      mitochondrial membrane to matrix-entrapped calcein (approximately 620 Da),
      indicating the opening of a large membrane pore. The MTP inhibitor cyclosporin A
      significantly stabilized delta psi(m) in single mitochondria, thereby slowing the
      voltage decay in averaged recordings. We conclude that the spontaneous
      depolarizations were caused by repeated stochastic openings and closings of the
      transition pore. The data demonstrate a much more dynamic regulation of membrane
      permeability at the level of a single organelle than predicted from ensemble
      behavior of mitochondrial populations.

PMID- 9545071
TI  - High microvascular endothelial water permeability in mouse lung measured by a
      pleural surface fluorescence method.
AB  - Transport of water between the capillary and airspace compartments in lung
      encounters serial barriers: the alveolar epithelium, interstitium, and capillary
      endothelium. We previously reported a pleural surface fluorescence method to
      measure net capillary-to-airspace water transport. To measure the osmotic water
      permeability across the microvascular endothelial barrier in intact lung, the
      airspace was filled with a water-immiscible fluorocarbon. The capillaries were
      perfused via the pulmonary artery with solutions of specified osmolalites
      containing a high-molecular-weight fluorescent dextran. An increase in perfusate
      osmolality produced a prompt decrease in surface fluorescence due to dye dilution
      in the capillaries, followed by a slower return to initial fluorescence as
      capillary and lung interstitial osmolality equilibrate. A mathematical model was
      developed to determine the osmotic water permeability coefficient (Pf) of lung
      microvessels from the time course of pleural surface fluorescence. As predicted,
      the magnitude of the prompt change in surface fluorescence increased with
      decreased pulmonary artery perfusion rate and increased osmotic gradient size.
      With raffinose used to induce the osmotic gradient, Pf was 0.03 cm/s at 23
      degrees C and was reduced 54% by 0.5 mM HgCl2. Temperature dependence
      measurements gave an Arrhenius activation energy (Ea) of 5.4 kcal/mol (12-37
      degrees C). The apparent Pf induced by the smaller osmolytes mannitol and glycine
      was 0.021 and 0.011 cm/s (23 degrees C). Immunoblot analysis showed approximately
      1.4 x 10(12) aquaporin-1 water channels/cm2 of capillary surface, which accounted
      quantitatively for the high Pf. These results establish a novel method for
      measuring osmotically driven water permeability across microvessels in intact
      lung. The high Pf, low Ea, and mercurial inhibition indicate the involvement of
      molecular water channels in water transport across the lung endothelium.

PMID- 9545073
TI  - First hominoid from the Miocene of Ethiopia and the evolution of the catarrhine
      elbow.
AB  - The first known fossil ape from the early-middle Miocene of Fejej, Ethiopia, is
      described here. The specimen, FJ-18SB-68, is a partial ulna from a locality dated
      by 40Ar/39Ar and paleomagnetic methods to a minimum age of 16.18 MYA. Compared to
      a variety of extant and fossil ulnae, FJ-18SB-68 is most similar to
      Turkanapithecus, Proconsul, and Pliopithecus, and appears to have been an
      arboreal quadruped with substantial forearm rotational mobility. Among the extant
      ulnae, canonical variates analysis successfully discriminates platyrrhines from
      catarrhines and within the latter, cercopithecoids from hominoids. Basal
      catarrhines (e.g., Aegyptopithecus) are platyrrhine-like in their morphology. Two
      basic trends appear to evolve from this generalized template: one with less
      mobile and more habitually pronated forearms, as seen in living and fossil
      cercopithecoids (including Victoriapithecus and Paracolobus), and another with
      greater forearm rotational mobility in fossil and modern hominoids. Primitive
      Miocene apes, including Proconsul, Turkanapithecus, and FJ-18SB-68, share with
      extant hominoids a more laterally positioned and laterally facing radial notch
      and an incipient trochlear keel. This morphology, along with a large insertion
      area for m. brachialis, suggests a departure from the more habitually pronated
      hand posture of monkeys and may indicate greater climbing abilities in these
      arboreally quadrupedal apes. Later Miocene apes, such as Oreopithecus and
      Dryopithecus share additional morphological features with hominoids, indicating
      considerable suspensory and climbing capabilities.

PMID- 9545074
TI  - Restoration of the type and palate of Ankarapithecus meteai: taxonomic and
      phylogenetic implications.
AB  - A small number of large hominoid specimens are known from the late Miocene of
      Turkey. (This paper focuses on the two specimens known until 1996. New fossils
      described by Alpagut et al. ([1996] Nature 382:349-351) are briefly discussed in
      this paper as well.) Among these, a fragmentary mandible is the type specimen of
      Ankarapithecus meteai. Another specimen, a partial face, is from the same taxon.
      Based on the morphology of this face, Ankarapithecus meteai was synonymized with
      Sivapithecus (Andrews and Tekkaya [1980], Paleontology 23:85-95). The facial
      specimen was recently restored by the authors, exposing much anatomy that had
      previously been obscured. The new anatomical details reveal many important
      differences from Sivapithecus and justify a revision of the nomen Ankarapithecus.
      Ankarapithecus was a large hominid (great apes and humans) in the clade that also
      includes Sivapithecus and Pongo. Sivapithecus and Pongo share derived characters
      not found in Ankarapithecus, which is thus the sister clade to the Sivapithecus
      Pongo clade. While the results of this analysis support the sister relationship
      of Sivapithecus and Pongo, there is some uncertainty regarding paleobiogeographic
      and taxonomic relationships to the large hominids from the Siwaliks. An
      Ankarapithecus-like taxon may have been ancestral to Sivapithecus, or an early
      Siwalik (Chinji formation) taxon, which predates both Sivapithecus sensu stricto
      and Ankarapithecus, may be ancestral to both.

PMID- 9545075
TI  - EMG study of hand muscle recruitment during hard hammer percussion manufacture of
      Oldowan tools.
AB  - The activity of 17 hand muscles was monitored by electromyography (EMG) in three
      subjects during hard hammer percussion manufacture of Oldowan tools. Two of the
      subjects were archaeologists experienced in the replication of prehistoric stone
      tools. Simultaneous videotapes recorded grips associated with the muscle
      activities. The purpose of the study was to identify the muscles most likely to
      have been strongly and repeatedly recruited by early hominids during stone tool
      making. This information is fundamental to the identification of skeletal
      features that may reliably predict tool-making capabilities in early hominids.
      The muscles most frequently recruited at high force levels for strong precision
      pinch grips required to control the hammerstone and core are the intrinsic
      muscles of the fifth finger and the thumb/index finger regions. A productive
      search for skeletal evidence of habitual Oldowan tool-making behavior will
      therefore be in the regions of the hand stressed by these intrinsic muscles and
      in the joint configurations affecting the relative lengths of their moment arms.

PMID- 9545076
TI  - Positional behavior and vertebral morphology in atelines and cebines.
AB  - Atelines are of particular interest to primate evolutionary studies because they
      converge with hominoids in postcranial anatomy, including the vertebral column.
      Currently, our understanding of ateline vertebral morphology is limited to mainly
      qualitative descriptions and functional interpretations based on general
      categories of positional behavior. Even less is known about the vertebrae of
      other platyrrhines. This study more closely examines vertebral form and function
      in atelines and cebines by combining direct field observations of axial postures
      and movements, assessments of spinal loading regimes, and a detailed vertebral
      morphometric analysis. Field observations (Corcovado, Costa Rica) on Ateles
      geoffroyi, Alouatta palliata, Cebus capucinus, and Saimiri oerstedii were
      quantified in conjunction with a morphometric analysis of ateline and cebine
      lumbar vertebrae. Hylobates was also included for comparison. Compared to Cebus
      and Saimiri, atelines engage more frequently in postures and locomotor behaviors
      that induce pronounced bending loads on the spine. All atelines share lumbar
      adaptations for resisting bending, including ventrodorsally elongated vertebral
      bodies and perpendicularly oriented transverse processes. Among atelines, lumbar
      region lengths and vertebral bodies are shortest in Ateles and Brachyteles,
      longest in Alouatta (resembling Cebus), and intermediate in Lagothrix. Compared
      to Cebus and all atelines, Saimiri has a relatively longer lumbar region, longer
      and less ventrodorsally expanded vertebral bodies, and more ventrally oriented
      transverse processes. These features accentuate bending loads, but increase the
      sagittal flexibility required for leaping. Vertebral convergence between
      hylobatids and atelines is more readily interpretable as a product of shared
      spinal loading patterns than shared positional behaviors.

PMID- 9545077
TI  - Morphological diversity of anatomical strepsirrhinism and the evolution of the
      lemuriform toothcomb.
AB  - The hypothesis that the vomeronasal organ has an important functional
      relationship with, and led to the evolution of, the prosimian toothcomb has not
      been well tested. This paper examines the diversity of anatomical strepsirrhinism
      across several mammalian taxa to determine if fossil and living strepsirrhine
      primates exhibit any derived characters that may highlight the functional link
      between the vomeronasal organ and the toothcomb, and to examine the potential
      importance of anatomical strepsirrhinism to toothcomb origins. Results indicate
      that extant gregarious lemuriforms are derived in having a relatively wide
      interincisal gap, providing an unobstructed line of communication between the
      vomeronasal organ and anterior rostral structures such as the toothcomb. This
      finding is consistent with the proposal that anatomical strepsirrhinism is
      functionally related to use of the toothcomb in grooming. However, the importance
      of the vomeronasal organ to toothcomb origins is less clear. If the morphology of
      adapiforms and non-gregarious lemuriforms is representative of the morphology of
      basal lemuriforms, then it can be inferred that early lemuriforms did not possess
      the wide-gap autapomorphy; hence, anatomical evidence discussed here cannot be
      used to rule out non-social hypotheses of toothcomb origins.

PMID- 9545078
TI  - Bicoronal synostosis in a child from historic Omaha Cemetery 25DK10.
AB  - Fragmentary cranial remains of a child from a commingled burial in a historic
      Omaha Cemetery (AD 1780-1800) exhibit bony fusion between the frontal, parietals,
      and sphenoid. The child's remains are consistent with a developmental age between
      newborn and 6 months postnatal. Radiological and morphological analyses confirm
      that this individual exhibits osteological signs pathognomic of bicoronal sutural
      synostosis, including deformation of the lateral orbital margin. This case,
      although fragmentary, significantly augments other archaeological cases of
      coronal synostosis reported in the literature. In addition, an extremely large
      bregmatic fontanel, expanded anterior cranial fossa, and bossed forehead compared
      with undeformed individuals suggest the child also suffered from increased
      intracranial pressure perhaps related to an associated hydrocephaly. Despite the
      deformity, the remains of this child were treated in much the same manner as
      other infant remains from the site, including the presence of red mercury pigment
      on the skeletal remains.

PMID- 9545079
TI  - Finger ridge-count asymmetry and diversity in Andean Indians and interpopulation
      comparisons.
AB  - A separate analysis of ulnar and radial finger ridge-counts, obtained from 115
      Aymara Indians (55 males and 60 females) of northern Chile, was performed. From
      these variables, directional asymmetry, fluctuating asymmetry, indices of
      bilateral asymmetry (square root of A2), and intraindividual diversity (s/square
      root of 5) were calculated for each sex. The results show that most bimanual
      differences for the ridge-counts are not statistically significant in the Aymara,
      except for radial counts in female first and second fingers (right hand means are
      larger), while most ulnar-radial differences are highly significant in both sexes
      (radial values exceed ulnar ones). Most sex differences do not reach statistical
      significance, although males have more ridge-counts, lower directional asymmetry,
      somewhat lower fluctuating asymmetry, and lower indices of asymmetry and
      diversity than females. As fluctuating asymmetry is not larger in males, the
      dermatoglyphic findings do not indicate support for the hypothesis that males are
      less canalized than females. In accordance with the findings of other authors,
      interpopulation comparisons in the indices of asymmetry and diversity show ethnic
      differences. Both indices tend to be low in samples of African ancestry, high in
      samples of European origin, and intermediate in the Aymara, while Indian groups
      are characterized by high asymmetry and low diversity values. Moreover, the data
      reveal a geographical trend in that asymmetry and diversity values tend to
      decrease from the northern to the southern hemisphere in populations of Europe,
      the Middle East, and Africa, thus indicating greater ridge-count variability and
      heterogeneity among fingers in northern populations. It is assumed that this
      gradient primarily reflects different degrees of miscegenation and
      heterozygosity.

PMID- 9545080
TI  - Technical note: chromosomal and mtDNA analysis of Oliver.
AB  - Oliver is an African ape whose species identity has been debated in the popular
      media and by various scientists since the early 1970s. Although decisive
      morphological data has never been adduced on Oliver, many reports indicated that
      Oliver was morphologically unusual for a chimpanzee, particularly in his habitual
      bipedal posture. In addition, his diploid chromosome number was reported to be
      inconsistent with either human or chimpanzee, but instead intermediate between
      those species. We performed standard chromosomal studies which demonstrated that
      Oliver had the diploid number expected for a chimpanzee (2N = 48) and that the
      banding patterns of his chromosomes were typical for a chimpanzee and different
      from both humans and bonobos. We also sequenced a 312 bp region of his
      mitochondrial DNA D-loop region. Results indicated a high sequence homology to
      the Central African variety of chimpanzee, Pan troglodytes troglodytes. The
      highest percent homology was observed with a previously characterized specimen
      from Gabon, strongly suggesting that Oliver originated from this region.

PMID- 9545081
TI  - How is membrane phospholipid biosynthesis controlled in neural tissues?
AB  - Phospholipids are the major constituents of cell membranes, and have numerous
      structural and functional roles in the nervous system. Although the metabolic
      pathways responsible for the syntheses of the phosphatides phosphatidylcholine
      (PtdCho), phosphatidylethanolamine (PtdEtn), and phosphatidylserine (PtdSer) are
      well understood, the mechanisms controlling these pathways in neural tissue have
      not been fully characterized. Recent studies have suggested that the main factors
      controlling PtdCho and PtdEtn synthesis by the Kennedy cycle tend to be the
      intracellular levels of key substrates for the biosynthetic enzymes, or changes
      in the activities of the rate-limiting enzymes. Moreover, different control
      mechanisms may operate, depending upon the functional state of the tissue.

PMID- 9545082
TI  - Cell culture models for reactive gliosis: new perspectives.
AB  - Reactive gliosis, which occurs in response to any damage or disturbance to the
      central nervous system, has been recognized for many years, but is still not
      completely understood. The hallmark is the increased expression of glial
      fibrillary acidic protein (GFAP), yet studies in GFAP knockout mice suggest that
      GFAP may not be required for an astrocyte to become hypertrophic. In this review,
      we describe a series of tissue culture models that have been established in order
      to address: 1) the biochemical phenotype of reactive astrocytes; 2) the factor
      and/or cell responsible for induction of gliosis; 3) the mechanisms by which one
      might block the induction. These models range from cultures of astrocytes, both
      neonatal and adult, to co-cultures of astrocytes with either neurons or
      microglia, to organ cultures. None is ideal: each addresses a different set of
      questions, but taken together, they are beginning to provide useful information
      which should allow a better understanding of the plasticity response of
      astrocytes to brain injury.

PMID- 9545083
TI  - Stimulation of L-type Ca2+ channel in growth cones activates two independent
      signaling pathways.
AB  - Although growth cones respond to various modulators of neurite outgrowth, such as
      neurotrophins, neurotransmitters, and cell adhesion molecules, the signal
      transducing mechanisms for these modulators in growth cones are unclear. Since
      recent studies have suggested that the signals of these modulators are mediated
      by Ca2+ influx through L-type voltage-sensitive Ca2+ channels (VSCCs) in the
      growth cone, we examined L-type VSCC-dependent signaling pathways, using isolated
      growth cones (IGCs) from developing rat forebrains. Binding assays revealed that
      L-type VSCC is enriched in growth cone membrane and gradually decreased in amount
      developmentally, while N-type VSCC has the opposite tendency. In intact IGCs, Bay
      K 8644 (BK, an L-type agonist) induced much more rapid elevation of [Ca2+]i than
      that in adult synaptosomes. Ca2+-dependent phosphorylation of GAP-43 and MARCKS
      protein by protein kinase C (PKC) was enhanced in the IGC by BK, resulting in the
      release of these proteins from the membrane, which is consistent with our recent
      report. In addition, the Ca2+-dependent degradation of brain spectrin (fodrin) by
      calpain was also enhanced by BK or GABA, consequently inducing the release of
      alpha-actinin from the membrane skeleton of the growth cones. The activities of
      PKC and calpain were not inhibited by inhibitors of the other, indicating that
      these reactions occur independently. Our results suggest that Ca2+ influx through
      L-type VSCCs activates two distinct signaling branches, probably in the different
      domains of the growth cone, i.e., Ca2+-dependent phosphorylation of GAP-43 and
      MARCKS protein, and Ca2+-dependent degradation of brain spectrin and the release
      of alpha-actinin by calpain.

PMID- 9545084
TI  - Granule cells of the internal granule layer have increased expression of GABA(A)
      receptor beta 2/beta 3 subunits.
AB  - We have examined the expression of GABA(A) receptor beta 2/beta 3 subunits from
      postnatal day 4 (P4) to P23. beta 2/beta 3 subunits are not detected in
      premigratory granule cells. Expression of beta 2/beta 3 was also low in granule
      cells found in the internal granule layers (IGLs) of P7 and P10 cerebella.
      However, between P10 and P16, the levels of beta 2/beta 3 increase substantially
      and reach high levels at P16-23. Because granule cells continue to migrate from
      the external granule layer (EGL) into the IGL after P10, this increase in the
      number of cells and the intensity of beta 2/beta 3 expression could be the result
      of a second wave of granule cells expressing beta 2/beta 3 that have migrated
      from the EGL. To test this hypothesis, migrating granule cells after P10 were
      eliminated by gamma-irradiation. Despite elimination of migrating granule cells,
      beta2/3 expression remained high in the IGLs of P16 irradiated animals similar to
      that observed in non-irradiated controls, suggesting that the increase of beta
      2/beta 3 is not due to the arrival of a new population of granule cells
      expressing GABA(A) receptors. To explore the possibility that the increase of
      beta2/beta 3 is triggered by synaptic activity, we cultured P10 cerebellar
      sections, free of mossy fiber inputs, for 6 days in vitro. As observed in vivo,
      beta 2/3 expression in the IGL of cultured slices continued to increase,
      suggesting that beta 2/3 expression could be triggered without synaptic inputs
      from mossy fibers.

PMID- 9545085
TI  - Bipotential roles of ceramide in the growth of hippocampal neurons: promotion of
      cell survival and dendritic outgrowth in dose- and developmental stage-dependent
      manners.
AB  - Ceramide is now regarded as a lipid messenger molecule involved in a variety of
      cellular processes, including growth, differentiation, and cell death.
      Previously, we demonstrated that ceramide is required for cell survival and
      dendritic growth of cerebellar Purkinje neurons (Furuya et al.: J Neurochem 65:
      1551-1561, 1995). Here, we show that ceramide plays growth-supportive roles in
      hippocampal neurons at immature stages of development. Application of cell
      permeable N-hexanoyl-D-erythro-sphingosine (C6-ceramide) at a concentration of 3
      microM promoted cell survival and dendritic outgrowth of the immature neurons. A
      structurally related compound, N-hexanoyl-D-erythro-dihydrosphingosine (C6
      dihydroceramide), was ineffective, showing a requirement of 4-5 double bonds in
      the sphingosine moiety for activity. Incorporation of 5-bromo-2'-deoxyuridine
      into neurons was not altered by the treatment with C6-ceramide, indicating that
      C6-ceramide did not facilitate neuronal proliferation but protected hippocampal
      neurons against basal cell death. The survival-promoting activity of C6-ceramide,
      however, appeared to be biphasic; C6-ceramide at a concentration of 10 microM
      caused retraction of the dendrites and detachment of the neurons from the culture
      plate followed by cell death. In contrast to the immature neurons, the treatment
      of mature hippocampal neurons with C6-ceramide did not support cell survival but
      caused nonnecrotic cell death, even at a concentration of 3 microM. These results
      suggest strongly that ceramide regulates the fate of hippocampal neurons,
      depending on its concentration and on the developmental stage.

PMID- 9545086
TI  - Axonal regrowth through a collagen guidance channel bridging spinal cord to the
      avulsed C6 roots: functional recovery in primates with brachial plexus injury.
AB  - Intraspinal implantation of a collagen guidance channel (CGC) to promote axon
      regeneration was investigated in marmosets with brachial plexus injury. After
      avulsion of the right C5, C6 and C7 spinal roots, a CGC containing (group B) or
      not (group A) a nerve segment, or a nerve graft (group C), was ventro-laterally
      implanted into the cord to bridge the ventral horn and the avulsed C6 roots. No
      spinal cord dysfunction was observed following surgery. Two months later, the
      postoperative flaccid paralysis of the lesioned arm improved. In five months, a
      normal electromyogram of the affected biceps muscle was recorded in all repaired
      animals. Motor evoked potentials were obtained with a mean amplitude of 13.37 +/-
      13.66 microV in group A, 13.21 +/- 5.16 microV in group B and 37.14 +/- 35.16
      microV in group C. The force of biceps muscle contraction was 27.33 +/- 20.03 g
      (group A), 24.33 +/- 17.03 g (group B) and 37.38 +/- 21.70 g (group C).
      Retrograde tracing by horseradish peroxidase showed labelled motoneurons
      ipsilaterally located in the C5 and C6 ventral horn, nearby the implantation
      site. The mean labelled neurons was 32.33 +/- 21.13, 219.33 +/- 176.29 and 64.33
      +/- 23.54 in group A, B and C respectively. Histological analysis presented
      numerous myelinated and unmyelinated regenerating axons in the implant of these
      animals. Statistical analysis did not show significant difference among the three
      repaired groups. Our results indicate that spinal neurons can regenerate through
      a CGC to avulsed nerve roots and induce motor recovery in primates.

PMID- 9545087
TI  - Differential distribution of beta-dystroglycan in rabbit and rat retina.
AB  - The distribution of the dystrophin-associated glycoprotein complex was
      investigated in rabbit and rat retina by using the monoclonal antibody 43DAG/8D5,
      which specifically recognizes beta-dystroglycan, a central component of the
      complex. In cryostat sections of retinae from both species, the authors observed
      staining of blood vessels, continuous labeling around the vitreal border, and
      strong immunoreactivity in the outer plexiform layer (OPL). Electron microscopy
      showed that the immunoreactivity associated with the vitreal border of the retina
      was the result of a subcellular concentration of beta-dystroglycan in the endfeet
      of Muller glial cells. A similar concentration was observed in endfeet of
      perivascular astrocytes in the region of contact with the capillary basal lamina.
      In the OPL, beta-dystroglycan was associated with the terminals of both rods and
      cones. The label was almost exclusively found outside the synaptic area and was
      particularly strong in the extensions of the photoreceptor terminals protruding
      into the OPL. In the OPL of the rabbit retina, the authors found additional
      immunoreactivity associated with the tips of postsynaptic horizontal and bipolar
      cell processes. These results show that the dystrophin-associated glycoprotein
      complex is subcellularly concentrated in photoreceptor terminals and glial cell
      endfeet, and that the rabbit retina differs from the rat retina by the additional
      expression of this complex in bipolar and horizontal cells.

PMID- 9545088
TI  - Mechanical injury to neuronal/glial cultures in microplates: role of NMDA
      receptors and pH in secondary neuronal cell death.
AB  - In vitro models of traumatic injury are useful adjuncts to animal models for
      studying mechanisms of post-traumatic cell death. Here we describe a new in vitro
      model in which reproducible levels of injury are delivered by a punch device that
      produces 28 parallel cuts in individual wells of 96-well microplates. Cell loss
      is measured by LDH assay or quantitative fluorometric assay for ethidium
      homodimer staining. Glial cultures show cell death restricted to the initial
      injury site, whereas neuronal/glial cultures demonstrate substantial spread of
      cell loss over time. We used this model to examine the role of pH and NMDA
      receptors in delayed post-traumatic injury. NMDA receptor blockade by dizocilpine
      (MK-801) or treatment with antisense oligodeoxynucleotides directed against
      NMDAR1 was neuroprotective. Decreased cell death was observed under acidic
      conditions whereas increased extracellular pH was associated with increased, MK
      801 sensitive cell loss. Advantages of our model include: reproducible trauma
      induction; rapid measurements of cell injury; and use of 96-well microplates
      which reduce time and cost. This model appears to be well-suited for the study of
      selected mechanisms of post-traumatic neuronal injury as well as for screening
      potential neuroprotective agents.

PMID- 9545089
TI  - TCR repertoire and cytokine profiles of cerebrospinal fluid- and peripheral blood
      derived T lymphocytes from patients with multiple sclerosis.
AB  - The cerebrospinal fluid (CSF) represents an important source of T lymphocytes
      that could be involved in the inflammatory response occurring in the central
      nervous system in multiple sclerosis (MS). In order to investigate whether the
      Vbeta gene usage of CSF T lymphocytes is restricted, we analyzed the TCR Vbeta
      expression in twelve CSF expanded by in vitro culture compared to the paired in
      vitro-stimulated peripheral blood T lymphocytes. The overexpression of one or two
      Vbeta genes was demonstrated in ten CSF, but the type of Vbeta over expressed
      varied from one patient to another. For one patient, the Vbeta repertoire was
      also investigated by single cell cloning. High frequency of BV6S7-expressing T
      cell clones was observed in the CSF while no BV6S7 clone was derived from the
      peripheral blood T lymphocytes suggesting that these cells could be involved in
      the immunopathological process in the central nervous system (CNS). The cytokine
      patterns of the T cell clones derived from the CSF- and peripheral blood-T
      lymphocytes of this patient were determined. The CSF T cell clones produced
      higher levels of cytokines than the peripheral blood T cell clones. The high
      frequency of IL-4-producing-T cell clones observed in CSF demonstrate that T
      cells which could downregulate the inflammatory process are present in the CNS.

PMID- 9545090
TI  - PCR detection of Y-specific sequences in patients with Ullrich-Turner syndrome:
      clinical implications and limitations.
AB  - Cytogenetic analysis of patients with Ullrich-Turner syndrome (UTS) may fail to
      detect low levels of Y chromosome mosaicism or Y-derived marker chromosomes. More
      sensitive polymerase chain reaction (PCR)-based tests have been developed;
      however, applicability of these data to prognosis of virilization and
      gonadoblastoma development has not been investigated adequately. We used a
      multiplex PCR-based method to detect two Y-specific sequences, SRY and AMGLY.
      Thirteen patients with UTS without cytogenetically detected Y chromosomes were
      studied. Y-specific sequences were detected in 5 patients by multiplex PCR. A
      cryptic translocation involving the Y chromosome was found in one patient with
      severe virilization of external genitalia and a male phenotype. Y chromosomal
      mosaicism was detected in peripheral blood and in both gonads of one patient, and
      only in the left gonad of another patient. Existence of a Y-derived marker was
      demonstrated in 2 patients, one of whom had no testicular tissue or virilization.
      Consistent with previous reports, we conclude that PCR is more sensitive than
      classical cytogenetic analysis and detects patients with Y-specific sequences in
      blood cells. However, the absence of Y-specific material in blood is not a
      sufficient reason to reject surgical treatment in case of virilization.

PMID- 9545091
TI  - Sweat electrolyte and cystic fibrosis mutation analysis allows early diagnosis in
      Brazilian children with clinical signs compatible with cystic fibrosis.
AB  - A total of 540 individuals with clinical signs suggestive of cystic fibrosis (CF)
      was studied. The sweat chloride was measured and the DF508, G542X, R553X, and
      W1282X mutations of the CF gene were screened by polymerase chain reaction (PCR).
      With this approach the diagnosis of CF was confirmed in 12 children, while 7
      additional cases, who are heterozygous for the DF508 mutation, have had minor
      clinical signs. The frequency of the DF508 allele among the 540 individuals was
      approximately 3%. The mean age of children diagnosed with CF was 1.81 years,
      which is significantly earlier than in other studies of the Brazilian population.
      We also demonstrated that this approach has important clinical implications for
      earlier and adequate treatment, which was shown to be fundamental for increasing
      significantly the quality of life and life expectancy. This is particularly true
      in countries such as Brazil where most CF cases remain undiagnosed, mainly in
      families of low socio-economical status.

PMID- 9545092
TI  - Errors of morphogenesis and developmental field theory.
AB  - Field theory provides a rational basis for birth defects terminology. During
      blastogenesis in higher metazoa, pattern formation in the primary field leads to
      the establishment of upstream expression domains of growth and transcription
      factors, which, in various permutations and at specific sites and times, lay down
      the pattern of progenitor fields. Further spatially coordinated, temporally
      synchronized, and epimorphically hierarchical morphogenetic events, mostly during
      organogenesis, lead to the attainment of final form in the secondary, epimorphic
      fields. Because of shared molecular determinants, spatial contiguity, and close
      timing of morphogenetic events during blastogenesis, most malformations arising
      during blastogenesis are polytopic, i.e., involving two or more progenitor
      fields, e.g., acrorenal, cardiomelic, gastromelic, or splenomelic anomalies.
      Defects of organogenesis tend to be monotopic malformations, e.g., cleft palate
      or postaxial polydactyly. We suggest that what were called "associations" (e.g.,
      VATER, schisis) be designated primary polytopic developmental field defects, or
      simply polytopic field defects, and that the term "association" be reserved for
      the original definition of a statistical combination of anomalies (mostly of
      organogenesis) [Spranger et al. (1982): J Pediatr 100:160-165]. If genetically
      caused or predisposed, all structures involved in a polytopic or monotopic
      malformation are genetically abnormal, whereas the parts secondarily affected as
      a consequence of a malformation sequence (e.g., spina bifida) are genetically
      normal. Polytopic field anomalies, per se, must be distinguished from pleiotropy,
      although such anomalies may constitute a part of pleiotropy (e.g., in trisomy
      18). Because they are downstream from pattern-forming events in the primary
      field, multiple anomalies of organogenesis more likely represent syndromal
      pleiotropy.

PMID- 9545093
TI  - Correlated heart/limb anomalies in Mendelian syndromes provide evidence for a
      cardiomelic developmental field.
AB  - Coordinated development of heart and limbs is suggested by a review of human
      abortus, chromosomal, and teratogenic syndromes, and characterized by an analysis
      of Mendelian disorders that affect the limbs, heart, or both (672, 202, or 107,
      respectively). Mendelian syndromes with altered limb patterns often include
      cardiac anomalies, as shown by limb duplications (34%), deficiencies (30%),
      hypoplasias (23%), or dysplasias (9.3%). Syndromes with particular cardiac
      anomalies, illustrated by VSD (85%) or ASD (90%), frequently include limb
      defects. Positional correlations of anterior (preaxial/conotruncal), posterior
      (postaxial/atrial), or lateral (mirror hand/atrial isometry) heart/limb anomalies
      are consistent with the existence of a cardiomelic developmental field.
      Vertebrate comparisons suggest an early D-V limb-heart gradient, influenced by
      the neural crest, with distal limb segments (80% of syndromic defects) at its
      dorsal extreme. The proposed cardiomelic field relates the genetic heterogeneity
      of disorders such as Holt-Oram syndrome to a cascade of molecules, including the
      brachyury, sonic hedgehog, bone morphogenetic protein, retinoic acid receptor,
      and transforming growth factor-beta families.

PMID- 9545094
TI  - Complex familial rearrangement of chromosome 9p24.3 detected by FISH.
AB  - We describe a newborn male with minor facial anomalies, pyloric stenosis, and a
      chromosome rearrangement that involves deletion and addition of material at
      9p24.3. Routine studies showed a 46, XY, add (9) (p24) karyotype. Fluorescence in
      situ hybridization (FISH) with two different whole chromosome probes for
      chromosome 9 failed to identify whether the additional material was derived from
      that chromosome. FISH with single copy YAC probes from 9p24 (D9S1858, D9S1813 and
      D9S54) showed a more complex rearrangement involving a deletion at D9S1858 but
      not at D9S1813 or D9S54. Parental chromosome studies demonstrated an apparently
      identical 9p abnormality in the patient's mother. This report describes a
      familial chromosome rearrangement in an abnormal child and his normal mother and
      demonstrates the use and limitations of FISH in characterizing chromosomal
      abnormalities.

PMID- 9545095
TI  - Lack of association between mutations in the folate receptor-alpha gene and spina
      bifida.
AB  - Defects of neural tube closure are among the most common of all human
      malformations. Epidemiological and genetic studies indicate that most of these
      defects are multifactorial in origin with genetic and environmental causes.
      Although periconceptional supplementation of the maternal diet with folic acid
      has been shown to reduce the recurrence and occurrence of neural tube defects
      (NTDs) by up to 70%, the underlying mechanism remains unknown. Folic acid enters
      cells of certain tissues via a receptor-mediated process known as potocytosis.
      The folate receptor alpha (FR-alpha) gene codes for the protein responsible for
      binding folate, which is the first, and only, folate-dependent step in folate
      transport. The FR-alpha exons, which code for mature protein and the intron-exon
      boundaries, were examined for mutations in three separate studies. Initial
      screening was performed by single-stranded conformational polymorphism (SSCP)
      analysis in a subset of 1,688 samples obtained from a population-based case
      control study of NTDs in California. In the second study, the DNA sequence of
      exons 5 and 6 was determined in a group of 50 NTD affected individuals. The final
      experiment involved using dideoxy fingerprinting (ddF) to screen a population
      based case-control sample of 219 individuals who were stratified into four sub
      groups on the basis of folate intake and pregnancy outcome. No polymorphism was
      detected in any of the four exons examined. It is unlikely that the beneficial
      effects of maternal folate supplementation in preventing NTDs acts through a
      mechanism involving pharmacological correction of a variant form of folate
      receptor alpha.

PMID- 9545096
TI  - A multicenter investigation with interphase fluorescence in situ hybridization
      using X- and Y-chromosome probes.
AB  - Twenty-six laboratories used X and Y chromosome probes and the same procedures to
      process and examine 15,600 metaphases and 49,400 interphases from Phaseolus
      vulgaris-leucoagglutinin (PHA)-stimulated lymphocytes. In Part I, each laboratory
      scored 50 metaphases and 200 interphases from a normal male and a normal female
      from its own practice. In Part II, each laboratory scored 50 metaphases and 200
      interphases on slides prepared by a central laboratory from a normal male and a
      normal female and three mixtures of cells from the male and female. In Part III,
      each laboratory scored 50 metaphases (in samples of 5, 10, 15, and 20) and 100
      interphases (in samples of 5, 10, 15, 20, and 50) on new, coded slides of the
      same specimens used in Part II. Metaphases from male specimens were scored as 98
      99% XY with no XX cells, and 97-98% of interphases were scored as XY with 0.04%
      XX cells. Metaphases from female specimens were scored as 96-97% XX with 0.03% XY
      cells, and 94-96% of interphases were scored as XX with 0.05% XY cells.
      Considering the data as a model for any probe used with fluorescence in situ
      hybridization (FISH), a statistical approach assessing the impact of analytical
      sensitivity on the numbers of observations required to assay for potential
      mosaicisms and chimerisms is discussed. The workload associated with processing
      slides and scoring 50 metaphases and 200 interphases using FISH averaged 27.1 and
      28.6 minutes, respectively. This study indicates that multiple laboratories can
      test/develop guidelines for the rapid, efficacious, and cost-effective
      integration of FISH into clinical service.

PMID- 9545098
TI  - Identification of heterozygotic carriers of 21-hydroxylase deficiency:
      sensitivity of ACTH stimulation tests.
AB  - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common
      autosomal-recessive disorder. To ascertain carrier status, adrenocorticotropin
      (ACTH) stimulation tests are often used. To determine the sensitivity of ACTH
      stimulation to detect heterozygotes and to correlate stimulated 17
      hydroxyprogesterone responses with molecular genotype, we compared molecular
      genetic analysis of the 21-hydroxylase (CYP21) gene with 17-hydroxyprogesterone
      responses at 30 min in 51 individuals. Molecular genotype analysis and ACTH
      stimulation tests were performed in healthy volunteers (n = 20) and relatives of
      patients with congenital adrenal hyperplasia (n = 31). Polymerase chain reaction
      (PCR) amplification, single-strand conformational polymorphism (SSCP) analysis,
      allele-specific oligonucleotide hybridization (ASOH) analysis, and restriction
      fragment length polymorphism (RFLP) analysis were utilized to screen for 14 CYP21
      mutations which account for >90% of the mutations associated with 21-hydroxylase
      deficiency. Molecular genotype analysis classified 28 individuals as
      heterozygotic carriers and 23 individuals as normal for all mutations tested. As
      a group, the heterozygotes had significantly greater stimulated 17
      hydroxyprogesterone responses at 10 and 30 min (P < 0.0005). However, on an
      individual basis, 14/28 (50%) genotyped heterozygotic carriers had stimulated 17
      hydroxyprogesterone concentrations, 17-hydroxyprogesterone/cortisol ratios, and
      17-hydroxyprogesterone incremental elevations indistinguishable from the
      genotyped normal individuals. Thus, a normal 17-hydroxyprogesterone response to
      ACTH stimulation testing does not exclude carrier status for 21-hydroxylase
      deficiency. Molecular genotype analysis is a more reliable method to determine 21
      hydroxylase heterozygotes.

PMID- 9545097
TI  - Autism and maternally derived aberrations of chromosome 15q.
AB  - Of the chronic mental disabilities of childhood, autism is causally least well
      understood. The former view that autism was rooted in exposure to humorless and
      perfectionistic parenting has given way to the notion that genetic influences are
      dominant underlying factors. Still, identification of specific heritable factors
      has been slow with causes identified in only a few cases in unselected series. A
      broad search for genetic and environmental influences that cause or predispose to
      autism is the major thrust of the South Carolina Autism Project. Among the first
      100 cases enrolled in the project, abnormalities of chromosome 15 have emerged as
      the single most common cause. The four abnormalities identified include deletions
      and duplications of proximal 15q. Other chromosome aberrations seen in single
      cases include a balanced 13;16 translocation, a pericentric inversion 12, a
      deletion of 20p, and a ring 7. Candidate genes involved in the 15q region
      affected by duplication and deletion include the ubiquitin-protein ligase (UBE3A)
      gene responsible for Angelman syndrome and genes for three GABA(A) receptor
      subunits. In all cases, the deletions or duplications occurred on the chromosome
      inherited from the mother.

PMID- 9545099
TI  - Caroline Crachami, the Sicilian dwarf (1815-1824): was she really nine years old
      at death?
AB  - Caroline Crachami (C.C.) considered to have had the Seckel syndrome was one of
      the most extreme cases of dwarfism ever recorded. Reputedly born in Sicily in
      1815, she attracted much attention when exhibited in England before her death on
      3 June 1824. Although she is said to have been 9 years old at death, published
      descriptions give her a dental age varying from 2 to 7 years. Examination of her
      skull in the Royal College of Surgeons of England demonstrated a more or less
      erupted complete deciduous dentition, with no erupted permanent teeth.
      Radiographs showed agenesis of several permanent teeth. It was concluded that the
      dental age of C.C. was 3 years (+/- 6 months). Perikymata were evident in the
      surface enamel encircling the crown of the partially exposed maxillary left first
      permanent molar. Their distribution and spacing were normal, with no evidence of
      developmental retardation. The distance between the periradicular bands in the
      root near the cement-enamel junction was also normal. We conclude that the dental
      age of C.C. was similar to her chronological age and that at death she was about
      3 and not 9 years old. The reason that she was said to be nearly 9 when exhibited
      in England we believe was related to financial considerations, as people would be
      generally less impressed with a dwarf only 3 years old. The new age we give C.C.
      has implications on the diagnosis of her medical condition.

PMID- 9545100
TI  - A growth on the tip of the nose, small appendages on both fifth fingers, and a
      sign from heaven in a child born in 1738.

PMID- 9545102
TI  - (Mis)classifying limb deficiencies: Reply to "Academicians are more likely to
      share each other's toothbrush than each other's nomenclature (Cohen, 1982)".

PMID- 9545101
TI  - Delineation of supernumerary marker chromosomes in 38 patients.
AB  - We present cytogenetic and clinical data on 38 patients with supernumerary marker
      chromosomes (SMCs). SMCs were characterized using a strategy combining classical
      banding techniques and molecular cytogenetic studies. Cases were ascertained
      prenatally, postnatally, and after fetal death. In 26 patients (68%), the SMC
      originated entirely from acrocentric chromosomes. Among these, most patients
      carried a der(15). In 11 patients (29%), they were of nonacrocentric origin,
      including 9 autosomal and 2 gonosomal marker chromosomes. In 1 patient the SMC
      was of partially acrocentric origin. Patients with small derivatives of
      chromosome 15 [der(15)] had a normal phenotype. Those with a larger der(15)
      showed phenotypical abnormalities. Patients with supernumerary marker chromosomes
      derived from chromosomes 13 or 21, and 14 appeared to have a low risk of
      abnormalities. Out of this group only 1 patient who carried an additional r(21)
      had physical anomalies. Patients with an SMC originating from chromosome 22
      showed physical abnormalities in 2 out of 6 cases. Supernumerary marker
      chromosomes identified as i(9p), i(12p), and der(18) were all associated with an
      abnormal phenotype. Two of the derivatives of chromosome 20 analyzed were
      correlated with a normal phenotype, while the carrier of the third one showed
      physical anomalies and motor retardation. Of 2 patients with an extra der(X), 1
      was normal and 1 showed an abnormal phenotype.

PMID- 9545103
TI  - FGFR2 gene mutation (Tyr375Cys) in a new case of Beare-Stevenson syndrome.

PMID- 9545104
TI  - Mosaic trisomy 18 male with normal intelligence who fathered a normal baby girl.

PMID- 9545105
TI  - Chronic thyroiditis as a favorable prognostic factor in papillary thyroid
      carcinoma.
AB  - A subgroup of patients with papillary thyroid carcinoma (PTC) also has chronic
      thyroiditis (CT) as an associated disease of the thyroid. To assess the
      prognostic value of CT in patients with PTC, we reviewed the histological slides
      of 2225 patients with PTC who had undergone surgery between 1971 and 1992. Of the
      2225 patients, 692 were excluded from the analysis because regional lymph nodes
      and/or nonneoplastic thyroid tissues were unavailable for histological
      assessment. The series included 281 patients with CT in nonneoplastic thyroid
      tissue and 1252 without CT. We performed statistical analyzes by the log-rank
      test and Cox's proportional-hazard method. Sixty-two (5.0%) of the 1252 patients
      without CT died of metastatic disease during the follow-up period and the relapse
      free 10-year survival rate was 85%. By contrast, only 2 (<1.0%) of the 281
      patients with CT died, and their relapse-free 10-year survival rate was 95%. The
      difference between patients with CT and those without CT in terms of relapse-free
      and overall survival was statistically significant (p < 0.0001). Risk factors for
      unfavorable outcome were age 45 years or more, absence of psammoma bodies, and
      absence of CT (p < 0.0001), followed by vascular invasion (p = 0.0007), male sex
      (p = 0.0013), and metastasis to regional lymph nodes (p = 0.047). Multivariate
      analysis indicated that all of these factors with the exception of gender were
      independent factors in the final model for overall survival. Chronic thyroiditis
      in the nonneoplastic thyroid of patients with PTC is a powerful prognostic factor
      for both relapse-free and overall survival.

PMID- 9545106
TI  - mRNA levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP
      9 and of their inhibitors TIMP-2 and TIMP-3 in normal thyrocytes and thyroid
      carcinoma cell lines.
AB  - Thyroid cancer can degrade basement membranes and invade tissues. This depends on
      a cascade of matrix metalloproteinases involving membrane-type 1 matrix
      metalloproteinase (MT1-MMP), MMP-2, and MMP-9. We analyzed the expression and
      role of these MMPs and their specific inhibitors TIMP-2 and TIMP-3 in human
      highly purified thyroid epithelial, C 643, HTh 74, SW 1736, and 8505 C thyroid
      carcinoma and thyroid-derived fibroblast cell cultures. The effect of phorbol
      myristate acetate (PMA), and of the inflammatory cytokines interleukin-1 (IL-1)
      and tumor necrosis factor-alpha (TNF-alpha) on MMP and TIMP mRNA levels were
      monitored by semiquantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) including an internal homologous competitor fragment. The highest MT1-MMP
      mRNA levels were found in thyroid-derived fibroblasts. The MT1-MMP mRNA
      expression was increased up to 10-fold by PMA, while all other growth factors
      tested had only negligible effects. The thyroid carcinoma cells themselves did
      not seem to play a crucial role in the production of MT1-MMP in thyroid tumors.
      Higher MMP-2 mRNA levels were found in all cell types investigated. The highest
      MMP-2 mRNA levels were determined in thyroid-derived fibroblasts and HTh 74
      cells. We found a lack of MMP-2 response to IL-1, TNF-alpha, and phorbol esters.
      In unstimulated cells, MMP-9 mRNA was found near the detection limit or at low
      levels. In nearly all cell types, treatment with PMA, IL-1, and TNF-alpha caused
      an increase of the MMP-9 mRNA levels. The results of basal and stimulated MMP-2
      and MMP-9 mRNA expression were confirmed at the protein level by gelatin
      zymography. TIMP-2 and TIMP-3 mRNAs were expressed at high levels. In contrast to
      the basal TIMP-3 mRNA levels, which varied over a great range, there were no
      striking differences the cell types from analyzing TIMP-2 mRNA. There were no or
      only slight stimulatory effects on TIMP-2 and TIMP-3 mRNA expression by IL-1, TNF
      alpha, and PMA. Taken together, most enzymes of the MT-MMP/MMP class of proteases
      facilitating invasion of thyroid tumor cells seem to have been produced by
      fibroblasts, not by the tumor cells themselves. However, some dedifferentiated
      thyroid tumor cell lines may be capable of secreting some of these enzymes, as in
      the case of HTh 74 cells.

PMID- 9545107
TI  - Treatment of micronodular lung metastases of papillary thyroid cancer: are the
      tumors too small for effective irradiation from radioiodine?
AB  - Our purpose was to determine if micronodular lung metastases from papillary
      thyroid cancer had diameters that were less than 1 mm and therefore of a size for
      which irradiation by radioiodine (131I) is inefficient. In five patients, lung
      metastases seen on computed tomography (CT) were enumerated and sized in the
      entire right lung and right upper lung giving volumes of measurable, ie, more
      than 1 mm diameter, tumors. Concentrations of diagnostic 131I were quantified
      scintigraphically in the same regions. Fractions of administered 131I per
      milliliter of tumor and the absorbed radiation from the subsequent treatments
      were calculated to see if the 131I levels in lungs were greater than expected for
      the visible tumor volumes. Two other patients manifesting similar findings had
      lung biopsies that were reviewed for size of metastases. The calculated fractions
      of administered activity per milliliter of tumor and the absorbed radiations from
      the treatments with 131I were exceptionally high. Biopsies revealed numerous
      tumors below the resolution of CT. We conclude that the fractions of administered
      activity and absorbed radiations of 131I in tumors were high because the measured
      tumor volumes underestimated the total tumor volumes. Many lung metastases were
      less than 1 mm in diameter.

PMID- 9545108
TI  - Changes in the thyroid technetium-99m scintigram after antithyroid and subsequent
      radioiodine treatment for solitary autonomous nodules.
AB  - In patients with solitary autonomous thyroid nodules, the treatment of choice is
      radioiodine (131I) therapy, eventually preceded by antithyroid drugs to avoid
      aggravation of hyperthyroidism. The aim of this study was to evaluate the
      scintigraphical results of 131I treatment when using antithyroid pretreatment.
      Twenty-four patients having a solitary autonomous thyroid nodule were studied. A
      technetium-99m (99mTc) pertechnetate scintigraphy was performed at the time of
      diagnosis, when serum thyrotropin (TSH) had been normal for about 3 months on
      antithyroid drug treatment, and finally when serum TSH was normalized after 131I
      treatment. The primary scintigram showed suppression of 99mTc pertechnetate in
      the paranodular thyroid tissue in all patients. The second scintigram showed
      normal uptake in the paranodular tissue in 22 patients and a continuing
      suppression of the paranodular tissue in 2 patients. The third scintigram showed
      a solitary adenoma in 14 patients with none or almost no uptake in the
      paranodular tissue, resembling the first scintigram. In 6 patients an adenoma was
      still present, but uptake was seen in the paranodular tissue; in 3 patients a
      homogenous uptake without any sign of the previous nodule, and in 1 patient very
      low uptake in the gland was seen. Four patients developed hypothyroidism in the
      follow-up period of approximately 1 year. Pretreatment with antithyroid drugs
      induced an increase in serum TSH, stimulating the paranodular tissue. 131I will
      therefore be distributed in the whole thyroid gland, and not only in the
      autonomous solitary nodule. After 131I treatment, we continuously found a
      solitary nodule with low uptake in the paranodular tissue in 20 of 24 patients.

PMID- 9545109
TI  - Induction of oral tolerance in human autoimmune thyroid disease.
AB  - Our laboratory has reported suppression of experimental autoimmune thyroiditis in
      mice by oral feeding with antigen. Based on these data, we considered it possible
      that oral feeding of animal thyroglobulin (TG) might induce tolerance to antigen
      in human autoimmune thyroid disease (AITD). Thirteen patients receiving thyroid
      hormone replacement with synthetic thyroxine (T4) (five patients with Graves'
      disease, treated with radioiodine 4 to 11 years ago and eight patients with
      Hashimoto's thyroiditis) were randomly assigned to a test group (switched to
      replacement with desiccated thyroid from porcine thyroids) and a control group
      (maintained on synthetic T4). Humoral and cellular immunologic parameters were
      evaluated in addition to clinical parameters before and every 3 months after the
      onset of study for a year. At the onset of study, there was no difference in
      clinical parameters, or humoral and cellular immunity to thyroid autoantigens,
      except a finding that one thyroid peroxidase (TPO) peptide (100 approximately
      119) appeared to stimulate peripheral blood mononuclear cells (PBMC) during in
      vitro microproliferation assay more in the test group than control group (p =
      0.051 by t test). Additionally, almost all of TPO and thyrotropin receptor
      extracellular domain (TSHR) peptides were slightly more stimulatory to PBMC from
      the test group than the control group, although this was not statistically
      significant. After treatment, all variables were analyzed at each time point
      between groups (t test), and also were analyzed over time in each group (analysis
      of variance, ANOVA). Among the clinical parameters, thyrotropin (TSH) levels were
      unchanged and equal. Total serum T4 levels (p < 0.05 at 6 and 12 months after
      treatment) and free thyroxine indices (FT4I) (p < 0.05 at all time points after
      treatment) were lower in the test group than the control group. This is an
      expected result of treatment with desiccated thyroid. We found no change over
      time nor any difference between groups at time points for titers of antibodies to
      thyroid autoantigens, ie, human TG, human TPO, and recombinant human TSHR from
      Escherichia coli. However, cellular immunity, measured by in vitro
      microproliferation of PBMC to peptides of TPO or TSHR, showed significant
      differences between groups. At 12 months, stimulatory indices (SI) of PBMC to six
      peptides, containing the indicated amino acids (764 approximately 95, 100
      approximately 119, 110 approximately 129, 261 approximately 275, 441
      approximately 448, 708 approximately 727) of 10 TPO peptides, and one peptide
      (145 approximately 163) of 14 TSHR peptides were lower in the test group than
      control group (p < 0.05). SI of PBMC to phytohemagglutinin, purified protein
      derivative from mycobacteria, and tetanus toxoid were not different between
      groups nor changed over time in any group. In conclusion, treating patients with
      AITD with an antigen related to the autoantigen TG did not produce changes in
      humoral immunity parameters, while cellular immunity to certain peptides were
      apparently suppressed. While the results are both surprising and intriguing, we
      need more evidence to justify the use of autoantigen as a form of immunospecific
      therapy in patients with AITD.

PMID- 9545110
TI  - Increased serum concentration of interleukin-5 in patients with Graves' disease
      and Hashimoto's thyroiditis.
AB  - We investigated serum levels of interleukin-5 (IL-5) in order to examine the role
      of T-helper 2 (Th2)-type immune response in the pathogenesis of autoimmune
      thyroid diseases. Serum levels of IL-5 were determined by a highly sensitive
      sandwich enzyme-linked immunosorbent assay in 42 patients with Graves' disease,
      32 patients with Hashimoto's thyroiditis, 12 patients with silent thyroiditis,
      and 21 normal controls. Compared with serum levels in normal subjects (5.8 +/-
      4.2 pg/mL), IL-5 was increased in patients with Graves' disease (16.4 +/- 16.7
      pg/mL, p < .01), and in patients with Hashimoto's thyroiditis (10.0 +/- 7.6
      pg/mL, p < .05), but not in patients with silent thyroiditis. There was no
      correlation between serum free thyroxine (FT4) and IL-5 levels. These data
      suggest an important role of the Th2-type immune response in the pathogenesis of
      Graves' disease and Hashimoto's thyroiditis.

PMID- 9545111
TI  - High frequency of T-cell lines responsive to immunodominant epitopes of
      thyrotropin receptor in healthy subjects.
AB  - In this study we analyzed the proliferative response to the extracellular domain
      of thyrotropin receptor (TSHR-ECD) of T-cell lines raised from healthy subjects.
      We found high frequencies of cell lines reactive to TSHR-ECD, ranging from 12% to
      37%. The response of the cell lines to a set of overlapping peptides of TSHR-ECD
      showed that the most recognized epitopes by T lymphocytes are on the C-terminal
      portion. In particular, the regions of residues 360-396 and 258-277 are
      immunodominant in T-lymphocyte reactivity. A group of cell lines specific for the
      peptides of TSHR-ECD lost the response to the peptides during time in culture.
      However, these lines were still responsive to TSHR extracellular domain. The
      cloning of one of these lines showed three types of T-cell clones: (1) CD4+
      clones (n = 4) highly responsive to the TSHR-ECD; (2) CD4+ clones (n = 4) low
      responsive to TSHR-ECD; (3) CD8+ clones (n = 9) not responsive to TSHR-ECD. The
      first group of clones was stable during time in culture, while the second group
      was characterized by the loss of the specific response to TSHR-ECD after some
      weeks from the first analysis. The observation of a spontaneous anergy in the
      second group of CD4+ clones suggests that mechanisms of control of the lymphocyte
      response to TSHR-ECD could be activated in vitro.

PMID- 9545112
TI  - Simultaneous measurement of free thyroxine and free 3,5,3'-triiodothyronine in
      undiluted serum by direct equilibrium dialysis/radioimmunoassay: evidence that
      free triiodothyronine and free thyroxine are normal in many patients with the low
      triiodothyronine syndrome.
AB  - We have devised a practical, sensitive and specific method for simultaneous
      measurement of free thyroxine (FT4) and free triiodothyronine (FT3) in undiluted
      serum by direct equilibrium dialysis radioimmunoassay (RIA). Two hundred
      microliters serum sample was dialyzed against buffer (pH 7.4) for 20 hours at 37
      degrees C and approximately 800 microL of the dialysate was used for measuring
      FT4 and FT3 simultaneously. The assay was set up in polystyrene tubes coated with
      anti-T4 antibody and available commercially for FT4 measurement (Quest-Nichols
      Institute, San Juan Capistrano, CA). The mean +/- SE (range) FT4 concentration
      (ng/dL) was 1.2 +/- 0.04 (0.7.0 to 2.30) in 54 normal subjects. It was
      significantly increased (3.6 +/- 0.4 [1.8 to 9.6], n = 20) in hyperthyroidism and
      clearly decreased (0.40 +/- 0.04 [1.10 to 0.70], n = 26] in hypothyroidism. All
      nonthyroid illness (NTI) patients had normal FT4 except 3, 2 of whom were on
      amiodarone and 1 had received heparin. Serum FT4 concentration was minimally
      elevated in 18 newborn cord blood serum (1.40 +/- 0.08 [0.90 to 2.2], cf. normal
      p < .05). The mean serum FT3 concentration (pg/dL) was 285 +/- 10 (134 to 454) in
      54 normal sera. It was clearly increased in hyperthyroidism (1033 +/- 98 [593 to
      2134], n = 20, p < .001). However, serum FT3 varied widely in hypothyroidism (27
      to 597, mean 235 +/- 24, NS) as did serum total T3 (19 to 175). Interestingly,
      however, the mean serum FT3 concentration was normal (273 +/- 28 [62 to 575, NS])
      in 25 NTI patients. All of these patients had low serum total T3 (46 +/- 5.0 [10
      to 84], ng/dL; normal 84 to 160, p < 0.001), while FT3 was clearly normal in 21
      of 25 patients and low in the remaining 4 patients. Similarly, among 18 newborn
      cord blood sera serum FT3 concentration was normal in 15 and subnormal only in
      the remaining 3 while all had clearly subnormal total T3 (28 to 74 ng/dL).
      CONCLUSIONS: (1) A practical, sensitive, and specific assay for simultaneous
      measurement of FT4 and FT3 is described; (2) FT3 is consistently elevated in
      hyperthyroidism while FT4 is elevated in most (approximately 85%) cases; (3) FT4
      is consistently decreased in hypothyroidism but FT3 varies widely; (4). Serum FT3
      concentration is normal in approximately 83% of patients with the low T3 syndrome
      in NTI and newborn cord blood serum. These data suggest that normal FT3 may
      explain clinical euthyroidism in many patients with the low T3 syndrome.

PMID- 9545113
TI  - Persistently increased gastrin and decreased pepsinogen concentrations in serum
      from some patients with Graves' disease of triiodothyronine-predominant type and
      common type.
AB  - This study aimed to investigate the cause of persistently increased serum gastrin
      concentration seen in some Graves' disease patients even when euthyroid during
      antithyroid drug treatment. The subjects studied consisted of three groups: 33
      patients with a common-type of Graves' disease, 14 with triiodothyronine (T3)
      predominant Graves' disease (characterized from previous studies as having potent
      immunologic abnormalities including greater concentrations of thyroid-stimulating
      antibodies together with larger goiter size), and a group of 20 normal subjects.
      Fasting serum gastrin concentrations in common Graves' disease patients were
      significantly higher than those of normal subjects (58.4 +/- 38.9 pmol/L vs. 37.8
      +/- 18.9 pmol/L [mean +/- SD], p < 0.05). The serum gastrin concentrations were
      even greater in T3-predominant Graves' disease patients than common Graves'
      disease patients (162.9 +/- 224.0 pmol/L vs. 58.4 +/- 38.9 pmol/L, p < .05).
      Serum pepsinogen I (PGI) concentrations were significantly lower in the T3
      predominant patient group than the common Graves' group (24.0 +/- 12.9 ng/mL vs.
      39.7 +/- 19.6 ng/mL, p < .05). Serum ratios of PG I to PG II were significantly
      lower in the T3-predominant Graves' disease patients than normal subjects (3.59
      +/- 2.66 vs. 5.97 +/- 1.56, p < .01). The ratios also had a significant (p < .05)
      inverse correlation with serum gastrin concentrations in T3-predominant Graves'
      disease patients. The results suggest that autoimmune gastritis is associated
      with Graves' disease, particularly in patients with potent thyroid-autoimmunity.

PMID- 9545114
TI  - Pentagastrin testing in patients with renal insufficiency: normal responsivity of
      mature calcitonin.
AB  - Calcitonin (CT) is the most sensitive tumor marker for medullary thyroid
      carcinoma available, but it lacks specificity. Chronic renal failure (CRF) is
      known to be associated with elevations of serum immunoreactive calcitonin. Using
      an immunoradiometric assay to detect only mature CT, we evaluated the basal CT
      level and its response to pentagastrin in 30 patients with CRF and compared these
      data with those obtained in 71 controls. Basal mature CT was significantly higher
      (p < 0.05) in patients with CRF (3.55 pg/mL) than in controls (2.00). Among these
      patients, 20% had basal CT levels more than 10 pg/mL with a maximum of 51 pg/mL.
      Peak CT values (highest value obtained 3 or 5 minutes after pentagastrin) were
      comparable in the two groups. Among patients with CRF, 10% had peak CT values
      greater than 30 pg/mL with a maximum of 53 pg/mL. In this group of patients, no
      correlation was found between CT (at any time during the test) and parathyroid
      hormone, calcium, phosphate, or creatinine clearance. Men had significantly
      higher CT values compared with women at each time point tested, including peak
      values. Patients with CRF, who have not yet undergone dialysis, have moderately
      elevated basal CT levels, but have normal pentagastrin-stimulated peak CT levels.

PMID- 9545115
TI  - Adrenal insufficiency after recurrent post-partum thyroiditis (post-partum
      Schmidt syndrome): a case report.
AB  - Polyglandular autoimmune syndrome (PGAS) type 2 (Schmidt syndrome) is
      characterized by the association of primary adrenocortical insufficiency with
      autoimmune thyroid disease, and/or insulin-dependent diabetes mellitus (IDDM). In
      this report we describe the occurrence of two episodes of post-partum thyroiditis
      (PPT) after a first and second pregnancy as well the development acutely of
      adrenal insufficiency after a second pregnancy. A family history of autoimmune
      thyroid disease and IDDM as well as positive antiadrenal and antithyroid
      antibodies and HLA typing is evidence for an underlying polyendocrine autoimmune
      syndrome. This case report provides further evidence that the immune system that
      is suppressed in pregnancy to tolerate the fetal allograft can rebound post
      partum to unmask polyendocrine autoimmune disorders such as adrenalitis and PPT
      in susceptible women.

PMID- 9545116
TI  - Radiation-induced painless thyrotoxic thyroiditis followed by hypothyroidism: a
      case report and literature review.
AB  - A 68-year-old woman presented with a small painless goiter and thyrotoxic
      symptoms immediately after 50-Gy external radiation for mucoepidermoid carcinoma
      of the submandibular gland. Elevated serum thyroid hormone and thyroglobulin
      levels, and undetectable serum thyrotropin level, together with extremely low
      thyroidal radioiodine uptake established the diagnosis of painless thyrotoxic
      thyroiditis. Thyroidal autoantibodies were negative. At follow-up without
      medication, all the symptoms disappeared, and laboratory abnormalities normalized
      within 6 months. One year later, the patient developed compensated hypothyroidism
      as indicated by elevated serum thyrotropin level with low normal serum thyroid
      hormone levels.

PMID- 9545117
TI  - The medical costs of social deprivation--whose job is it anyway?

PMID- 9545118
TI  - The emerging role of post-prandial hyperglycaemic spikes in the pathogenesis of
      diabetic complications.

PMID- 9545119
TI  - The blood glucose lowering effects of exercise and glibenclamide in patients with
      type 2 diabetes mellitus.
AB  - Physical exercise is associated with a fall in serum insulin levels, whereas
      sulphonylurea administration increases insulin release. To date, the opposing
      effects of exercise and sulphonylurea administration have not been systematically
      studied in Type 2 diabetic patients, who are not infrequently treated with
      sulphonylureas. In this study nine patients with Type 2 diabetes mellitus were
      subjected to four treatments in random order on separate days: (A) endurance
      exercise after the administration of 3.5 mg glibenclamide; (B) as A but given
      only 1.75 mg glibenclamide; (C) as A but with placebo; (D) rest and
      administration of 1.75 mg glibenclamide. Exercise and placebo resulted in only a
      small decrease in glycaemia. Rest and administration of 1.75 mg glibenclamide led
      to a moderate but steady fall in blood glucose concentrations. If glibenclamide
      administration and exercise were combined, blood glucose concentrations declined
      more markedly. Serum insulin concentrations showed a physiological decrease
      during exercise and placebo administration. If patients rested after
      administration of glibenclamide serum insulin levels rose and remained elevated.
      When exercise and glibenclamide were combined the rise in serum insulin levels
      was blunted and insulin levels fell once exercise was begun. Thus, exercise
      attenuates the glibenclamide induced increase in serum insulin in moderately
      hyperglycaemic Type 2 diabetic patients. Nevertheless, exercise has a substantial
      hypoglycaemic effect in glibenclamide treated Type 2 diabetic patients.

PMID- 9545120
TI  - Counterregulatory hormones in insulin-treated diabetic patients admitted to an
      accident and emergency department with hypoglycaemia.
AB  - The aim of the study was (1) to describe hormone responses in insulin-induced
      hypoglycaemia and (2) to investigate if a combined treatment with intravenous
      glucose and intramuscular glucagon (group A) would improve glucose recovery as
      compared to treatment with intravenous glucose alone (group B). Eighteen adult
      patients with insulin-treated diabetes mellitus admitted to the Accident and
      Emergency Department with hypoglycaemia (plasma glucose 1.23 +/- 0.15 mmol l(-1)
      on admission) were randomized to one of the above treatments and plasma glucose
      and counterregulatory hormones were measured before and 30-120 min after
      treatment. Pre-treatment counterregulatory hormone concentrations were
      significantly lower than hormone concentrations during induced hypoglycaemia in
      healthy control subjects but significantly higher than healthy fasting
      concentrations for plasma adrenaline (p = 0.020), glucagon (p = 0.008), growth
      hormone (p = 0.011), and cortisol (p<0.00001). Thus, although glucagon and
      adrenaline responses may be absent when studying Type 1 diabetic patients in the
      experimental setting, both hormones increase to a significant extent in 'real
      life' hypoglycaemia in this patient group, although to a lesser degree than might
      be expected. Plasma glucose did not differ significantly between the two
      treatments at any time point. Despite access to food, one of four patients in
      group B and one of five patients in group A had plasma glucose below 4.0 mmol l(
      1) after 120 min. In conclusion, low yet significantly elevated concentrations of
      adrenaline and glucagon were found in diabetic patients admitted with severe
      hypoglycaemia to an Accident and Emergency Department.

PMID- 9545121
TI  - Social deprivation and mortality in adults with diabetes mellitus.
AB  - To investigate the relationship between measures of social deprivation and
      mortality in adults with diabetes, data from 2104 randomly selected adults (> 16
      years of age) with Type 1 and Type 2 diabetes mellitus from 8 hospital out
      patient departments were analysed. A total of 38% of subjects had Type 1
      (diagnosed before the age of 36 years and treated with insulin), 55% were male
      and 85% Caucasian. During a follow-up period (mean (SD) of 8.4 (0.9) years), 293
      (14%) of the subjects died, the most commonly recorded cause of death being
      cardiovascular disease. Duration adjusted odds ratios (OR) and 95% confidence
      intervals (CI) were calculated separately for Type 1 and Type 2 subjects. The
      mortality rates for men were higher than for women (Type 1: OR 1.27, CI 0.61
      2.62; Type 2: OR 1.79, CI 1.27-2.52); were higher for those of lower vs higher
      social class (Type 1: OR 1.34, CI 0.61-2.96; Type 2: OR 2.0, CI 1.41-2.85); and
      were higher for those who left school before 16 years of age compared to those
      who left school at or after 16 years of age (Type 1: OR 3.98, CI 1.96-8.06; Type
      2: OR 2.86, CI 1.93-4.25). Subjects who were unemployed had a higher mortality
      rate than those employed at the time of the study (Type 1: OR 3.10, CI 1.67-5.79;
      Type 2: OR 2.88, CI 2.12-3.91) and those living in council housing had a greater
      mortality than those who were living in other types of housing (Type 1: OR 2.57,
      CI 1.35-4.91, Type 2: OR 2.76, CI 2.05-3.73). Also for both Type 1 and Type 2
      subjects mortality was significantly higher in those subjects who had a least one
      diabetic complication at baseline and reported one or more hospital admissions in
      the previous year and in Type 2 subjects with poor glycaemic control. After
      adjusting for duration of diabetes, hospital admissions, and the presence of
      diabetic complications, being unemployed, male, in poor glycaemic control (Type 2
      only), and less educated were significant risk factors for mortality (p<0.001).
      These results suggest that there are important indicators of social deprivation
      which predict mortality over and above diabetic health status itself. Locally
      targeted action will be required if these inequalities in health experienced by
      people with diabetes are to be reduced.

PMID- 9545122
TI  - Low educational status is a risk factor for mortality among diabetic people.
AB  - Diabetes mellitus and its complications are an important cause of mortality in
      Western populations. The purpose of the present study was to examine the
      relationship between self-reported diabetes mellitus, gender, attained level of
      education, and socio-economic resources to all-cause mortality risk in a simple
      random sample of 39055 subjects, aged 25 to 74 years. Follow-up data were
      obtained for a maximum of 16 years, from baseline (1979-1985) to 31 December
      1995. Diabetic males (2.2% of the male study group) had a relative risk (RR) for
      total mortality of 2.24 (CI = 1.96-2.57), adjusted for age, education, marital
      status, housing tenure, and car ownership, compared with non-diabetic males. The
      corresponding figure for females with diabetes (1.9%) was RR = 3.67 (CI = 3.16
      4.27). Diabetic women had the highest age-adjusted mortality risk for coronary
      heart disease (CHD) of 8 compared with non-diabetic women. The corresponding RR
      for men was just below 3 (p<0.0001). Males and females (with and without
      diabetes) of low attained educational level had a RR = 1.26 (CI = 1.15-1.39) and
      RR = 1.54 (CI = 1.31-1.81), respectively. When analysing all people with diabetes
      separately, adjusting for sex and age, low-educated subjects had a 40% excess all
      cause mortality compared with high-educated subjects. We conclude that diabetic
      women have a very high relative risk for CHD mortality compared to non-diabetic
      women. Furthermore, diabetic people with a low attained level of education, have
      an increased vulnerability to, and a higher total mortality.

PMID- 9545123
TI  - Size at birth, maternal weight, and type 2 diabetes in South India.
AB  - Recent research in Europe and the USA has shown that adults who had a low
      birthweight or who were thin at birth with a low ponderal index
      (birthweight/length3) tend to be insulin resistant and have an increased risk of
      developing Type 2 diabetes mellitus. Low birthweight and Type 2 diabetes are
      common in India. We have studied glucose and insulin metabolism in 506 men and
      women (aged 39-60 years) born in a hospital in Mysore, South India, which kept
      detailed obstetric records from 1934. The prevalence of Type 2 diabetes was 15%.
      In contrast to Western populations, higher rates were found in men and women who
      were short at birth (p = 0.07) and had a high ponderal index (p = 0.05). Their
      mothers tended to be heavier than average during pregnancy (p = 0.004). Higher
      ponderal index at birth was also associated with a lower 30 minute insulin
      increment (p = 0.009), a marker of reduced beta cell function. We speculate that
      the rise in Type 2 diabetes in Indian urban populations may have been triggered
      by mild obesity in mothers, leading to glucose intolerance during pregnancy,
      macrosomic changes in the fetus, and insulin deficiency in adult life.

PMID- 9545124
TI  - Peripheral sensory nerve dysfunction in children and adolescents with type 1
      diabetes mellitus.
AB  - The aim of the present study was to investigate peripheral sensory nerve function
      in diabetic children and adolescents without neurological symptoms. Ninety-two
      children and adolescents with Type 1 (insulin-dependent) diabetes mellitus (mean
      +/- SD age: 14.2 +/- 2.1 years, diabetes duration: 5.8 +/- 3.0 years) and 80
      healthy control subjects (age: 13.8 +/- 2.2 years) matched for age, sex, body
      mass index, and height standard deviation score were involved in the study. Using
      a sine-wave transcutaneous stimulator, current perception threshold (CPT) testing
      at 2000, 250 and 5 Hz was performed on the left median and peroneal nerves.
      Diabetic children had increased CPT at 2000 Hz on both nerves as compared to the
      control group (median (interquartile range), median nerve: 2.43 (2.20-3.43) vs
      1.80 (1.51-2.60) mA, p = 0.02; peroneal nerve: 3.51 (2.81-4.82) vs 2.70 (2.04
      3.70) mA, p = 0.01). Twenty-one (23%) of patients had CPT values higher than that
      of any healthy individual. Of these, elevated CPT was observed in 9 (9.8%)
      patients on the median nerve, in 8 (8.7%) patients on the peroneal nerve, and in
      4 (4.3%) patients on both median and peroneal nerves. Using multiple logistic
      regression analysis, worse long-term metabolic control and advanced puberty were
      independently predictive of peripheral sensory nerve dysfunction as the dependent
      variable (adjusted OR (95% CI): 3.4 (1.2-6.2), p = 0.01, and 2.8 (1.1-5.6), p =
      0.03, respectively). In conclusion, evidence of peripheral sensory nerve
      dysfunction is not rare in children and adolescents with diabetes and can be
      demonstrated by CPT testing in asymptomatic patients. Poor metabolic control is a
      risk factor for such subclinical neuropathy, and pubertal development may be
      involved in the pathogenesis of diabetic peripheral neuropathy.

PMID- 9545125
TI  - Reproducibility and comparability of insulin sensitivity indices measured by
      stable-label intravenous glucose tolerance test.
AB  - We have investigated the reproducibility of (1) insulin sensitivity (S*I) and
      glucose effectiveness (S*G) as measured by the stable-label (one compartment)
      minimal model, and (2) insulin sensitivity (S*Ib), plasma clearance rate (PCR),
      basal hepatic output (HGOb), and total hepatic glucose output (HGO0-240) as
      measured by the novel stable-label two compartment model of glucose disappearance
      during labelled intravenous glucose tolerance test (IVGTT) using 6,6-(2)H
      glucose. Ten normal male subjects were studied on two occasions one week apart.
      Both models provided estimates of all indices with acceptable precision (CV of
      parameter estimates < or =50%). The within subject CVs of S*I and S*Ib were
      comparable (17% vs 19%) as were the within subject CVs of S*G and PCR (13% vs
      16%). A highly significant linear relationship was observed between S*Ib and S*I
      (0.303 +/- 0.046 ml kg(-1) min(-1) per mU l(-1) vs 13.04 +/- 1.89 10(-4) min(-1)
      per mU l(-1), y = 0.0037 x + 0.0002, r = 0.90, p < 0.001; mean +/- SE), but not
      between PCR and S*G (1.98 +/- 0.15 ml kg(-1) min(-1) vs 0.0089 +/- 0.0005 min(
      1), rs = 0.34, NS). The two compartment model provided a plausible time-profile
      of hepatic glucose output during IVGTT, reproducible estimates of HGOb (1.96 +/-
      0.18 mg kg(-1) min(-1), 15%; mean +/- SE, within subject CV), and a highly
      reproducible HGO0-240 (7%; within subject CV). We conclude that the stable-label
      (one compartment) minimal model and the stable-label two compartment model
      provide reproducible estimates of parameters of glucose kinetics in normal
      subjects. Insulin sensitivity indices estimated by the two models are strongly
      linearly related.

PMID- 9545126
TI  - Human insulin analogue [LYS(B28), PRO(B29)]: the ideal pump insulin?
AB  - The short-acting insulin analogue lispro ([LYS(B28), PRO(B29)] is absorbed from
      the subcutis more rapidly than soluble insulin (S). To compare the clinical
      effectiveness of lispro vs S, 11 Type 1 patients using continuous subcutaneous
      insulin infusion (CSII) therapy (6 F, 5 M, age 30 +/- 2.5 years, diabetes
      duration 14 +/- 1.0 years, BMI 24.0 +/- 0.8 kg m(-2), HbA1c 6.5 +/- 0.2%) were
      studied in an open, randomized, crossover study for 6 months (3 months lispro and
      3 months S or vice versa). During lispro treatment mean fasting and 2 h
      postprandial blood glucose were lower compared to the S phase (fasting 6.5 +/-
      0.4 vs 7.5 +/- 0.4 mmol l(-1) (NS), postprandial 6.8 +/- 0.3 vs 8.3 +/- 0.3 mmol
      l(-1), p = 0.03). In patients treated first with lispro HbA1c levels improved
      from 6.3 +/- 0.2% to 5.7 +/- 0.3%; On reversion to S HbA1c increased to 6.2 +/-
      0.2%. In the group treated first with S, HbA1c fell (6.7 +/- 0.4% vs 6.5 +/-
      0.3%) and then improved further to 6.3 +/- 0.3% with lispro. None of these
      changes were significant. There was no significant difference with respect to
      hypoglycaemic or other adverse events. It can be concluded that lispro in CSII
      therapy is safe and may improve postprandial glucose excursions.

PMID- 9545127
TI  - A comparison of digital retinal images and 35 mm colour transparencies in
      detecting and grading diabetic retinopathy.
AB  - We compared digital retinal images and 35 mm colour transparencies taken with the
      Canon CR5 retinal camera for the detection and grading of diabetic retinopathy in
      a clinical setting, in a randomized, blinded study of diabetic patients with a
      spectrum of severity of diabetic retinopathy. Forty patients were photographed,
      giving a total of 75 eyes including non-diabetic eyes as controls. Images were
      graded according to the validated European guidelines. There was exact agreement
      between grades obtained from both the 2 field 45 degrees 35 mm colour
      transparencies and digital images in 93.3% (70/75) of eyes, with Cohen's Kappa
      statistic for the comparison being 0.92. Overall, when grading from the digital
      images 5.3% (4/75) eyes were undergraded with three cases of sight threatening
      diabetic retinopathy (STDR) graded as non-sight threatening (NSTDR) (3/48, 6.3%).
      One eye was overgraded (1/75, 1.3%). Two of the three cases of STDR undergraded
      as NSTDR had small numbers of intra-retinal microvascular abnormalities (IRMA)
      discernible on the colour transparencies but which were not visible from the
      digital image. The third had multiple small cotton wool spots graded as laser
      photocoagulation scars from the digital images. In conclusion there is good to
      excellent agreement between retinopathy grades using the Canon CR5 digital
      retinal imaging system compared to 35 mm colour transparencies.

PMID- 9545128
TI  - Instant electronic imaging systems are superior to Polaroid at detecting sight
      threatening diabetic retinopathy.
AB  - Polaroid photography in diabetic retinopathy screening allows instant image
      availability to enhance the results of ophthalmoscopy. Retinal cameras are now
      being developed which use video/digital imaging techniques to produce an instant
      enlarged retinal image on a computer monitor screen. We aimed to compare one such
      electronic imaging system, attached to a Canon CR5 45NM, with standard Polaroid
      retinal photography. Two hundred and thirteen eyes from 107 diabetic patients
      were photographed through dilated pupils by both systems in random order and the
      images were analysed blind. Diabetic retinopathy was present in 58 eyes of which
      55/58 (95%) were detected on the electronic image and only 49/58 (84%) on the
      Polaroid. Of 34 eyes requiring ophthalmologist referral according to standard
      European criteria, 34/34 (100%) were detected on the electronic image and only
      24/34 (71%) on the Polaroid. Side by side comparisons showed electronic imaging
      to be superior to Polaroid at lesion detection. Using linear analogue scales, the
      patients assessed the electronic imaging photographic flash as less uncomfortable
      than the Polaroid equivalent (p < 0.0001). Other advantages of electronic imaging
      include: ready storage of the images with other patient clinical data on the
      diabetes computerized register/database; potential for image enhancement and
      analysis using image analysis software and electronic transfer of images to
      ophthalmologist or general practitioner. Electronic imaging systems represent a
      potential major advance for the improvement of diabetic retinopathy screening.

PMID- 9545129
TI  - Central pontine myelinolysis and ataxia: an unusual manifestation of
      hypoglycaemia.
AB  - Hypoglycaemia is common in people with diabetes who aim to achieve good blood
      glucose control. Severe hypoglycaemia presents with evidence of neurological
      dysfunction, such as inability to concentrate, confusion, seizures, and coma.
      Such disturbances are reversible on correction of the hypoglycaemia. Infrequently
      there may be a focal neurological deficit and we report one such case presenting
      with cerebellar symptoms following an episode of severe hypoglycaemia. A magnetic
      resonance scan showed features consistent with the presence of central pontine
      myelinolysis. The symptoms resolved within a few months with only minimal
      residual neurological deficit.

PMID- 9545130
TI  - Use of a prostacyclin analogue in cholesterol crystal embolism.
AB  - The prognosis of cholesterol embolism is often poor, and no treatment is
      presently available. We report the use of a stable prostacyclin analogue in
      treating cholesterol embolism in a diabetic patient with arteriopathy. As a sole
      therapy, it improved cutaneous manifestations and pain, in parallel with an
      increased transcutaneous oxymetry. We think that prostacyclin analogues are novel
      candidates for the treatment of cholesterol embolism.

PMID- 9545131
TI  - Porcine reproductive and respiratory syndrome.
AB  - In 1987, porcine reproductive and respiratory syndrome (PRRS) was recognized in
      the USA as a new disease of swine causing late-term reproductive failure and
      severe pneumonia in neonatal pigs. The syndrome is caused by an RNA virus
      referred to as PRRS virus (PRRSV), which is classified in the family
      Arteriviridae. Swine macrophages are the only indigenous cell type known to
      support PRRSV replication. Direct contact between infected and naive pigs is the
      predominant route of PRRSV transmission. Exposure of a mucosal surface to PRRSV
      leads to virus replication in regional macrophages, a prolonged viremia and
      systemic distribution of virus to other macrophage populations. Reproductive
      failure induced by PRRSV infection in late-gestation sows is characterized by
      premature farrowing of stillborn, partially autolyzed, and mummified fetuses.
      Pneumonia caused by PRRSV infection is more severe in young pigs compared to
      adults and may be complicated by concurrent bacterial infections. Gross lung
      lesions associated with PRRSV infection vary from none to diffuse consolidation.
      In addition, multiple lymph nodes may be markedly enlarged. Microscopically,
      PRRSV-pneumonia is characterized by multifocal, interstitial thickening by
      macrophages and necrotic cell debris in alveoli. Other less common microscopic
      lesions of PRRSV infection include myocarditis, vasculitis, encephalitis, and
      lymphoid hypertrophy and hyperplasia. In acute or subacute PRRSV infections,
      serum and lung are the best specimens for diagnosis. Persistent PRRSV infections
      can be produced by transplacental or intranasal infection. Persistent PRRSV
      infections are an important factor for virus survival and transmission within a
      swine herd and will complicate control programs.

PMID- 9545132
TI  - Lesions caused by cardiovascular flukes (Digenea: Spirorchidae) in stranded green
      turtles (Chelonia mydas).
AB  - Evidence of infection with spirorchid flukes (Digenea: Spirorchidae) was sought
      at necropsy of 96 stranded green turtles, Chelonia mydas, that were examined
      during the course of a survey of marine turtle mortality in southeastern
      Queensland, Australia. Three species of spirorchid (Hapalotrema mehrai, H.
      postorchis, and Neospirorchis schistosomatoides) were identified. Severe disease
      due to spirorchid fluke infection (spirorchidiasis) was implicated as the
      principal cause of mortality in 10 turtles (10%), and appeared to be one of
      multiple severe problems in an additional 29 turtles (30%). Although flukes were
      observed in only 45% of stranded C. mydas in this study, presumed spirorchid
      fluke infection was diagnosed in an additional 53% of turtles, based principally
      on characteristic necropsy lesions and to a lesser extent on the
      histopathological detection of spirorchid eggs. Characteristic necropsy lesions
      included miliary spirorchid egg granulomas, which were observed most readily on
      serosal surfaces, particularly of the small intestine. Cardiovascular lesions
      included mural endocarditis, arteritis, and thrombosis, frequently accompanied by
      aneurysm formation. Resolution of thrombi was observed to occur via a combination
      of granuloma formation about indigestible components (spirorchid fluke egg
      shells) and exteriorization through the vessel wall, which resulted in
      granulomatous nodules on the adventitial surface. Septic aortic thrombosis
      complicated by disseminated bacterial infection, observed in five turtles, was
      recorded for the first time. Egg granulomas were ubiquitous in turtle tissues
      throughout this study. Although they generally appeared to be mild or incidental
      lesions, they were occasionally associated with severe multifocal granulomatous
      pneumonia or meningitis.

PMID- 9545133
TI  - Vesicular and ulcerative dermatopathy resembling superficial necrolytic
      dermatitis in captive black rhinoceroses (Diceros bicornis).
AB  - The histopathology, clinical presentation, and epidemiology of a cutaneous and
      oral mucosal disease affecting 40 black rhinoceroses (Diceros bicornis) at 21
      zoological parks (50% of the captive US population) were investigated. Twenty
      seven biopsies were examined from recent lesions, and clinical information was
      available from 127 episodes. The cutaneous lesions began as plaques that
      progressed to vesicles, bullae, or ulcers. Lesions waxed and waned in individual
      cases. Lesions were predominantly bilaterally symmetrical, affecting pressure
      points, coronary bands, tips of the ears and tail, and along the lateral body
      wall and dorsum. Oral lesions were first noticed as ulcers and were present on
      the lateral margins of the tongue, palate, and mucocutaneous junctions of the
      lips. All recent lesions had similar histopathologic findings of prominent
      acanthosis, hydropic degeneration of keratinocytes in the stratum spinosum,
      spongiosis, intraepithelial vesicles, and parakeratosis without dermal
      inflammation. Chronic lesions were ulcerated. No pathogens were identified by
      culture or electron microscopy. Most episodes coincided with stress events
      (transportation, sudden cold temperatures, intraspecific harassment, estrus,
      advanced pregnancy) or concurrent diseases (toxic hepatopathy, hemolytic anemia,
      respiratory or urinary tract infections). Affected rhinoceroses usually were
      lethargic and had weight loss. Affected rhinoceroses also had lower hematocrit,
      serum albumin, and cholesterol values than captive healthy or wild rhinoceroses.
      The clinical patterns and histopathologic findings are similar to those of
      superficial necrolytic dermatitis in dogs and necrolytic migratory erythema in
      humans. The high prevalence of this skin disease in captive black rhinoceroses
      under many circumstances suggests that their epidermis is acutely sensitive to
      any disruption of metabolic homeostasis. We propose that metabolic changes
      secondary to a stress response from maladaptation or nutritional inadequacy of
      captive diets may contribute to the development of this disease in rhinoceroses
      without hepatopathies.

PMID- 9545134
TI  - Immunohistochemical characterization of inflammatory cells in brains of dogs with
      granulomatous meningoencephalitis.
AB  - The inflammatory cells of eleven dogs with canine granulomatous
      meningoencephalitis were characterized immunohistochemically. Macrophages were
      identified by antibodies directed against lysozyme and the DH82 antigen
      (expressed by cells of a malignant histiocytosis). T cells were demonstrated by
      CD3, CD43, and CD45R antigen, and B cells by immunoglobulin G and immunoglobulin
      M expression. Furthermore, staining for the major histocompatibility complex
      (MHC) class II antigen was evaluated. Diseased animals ranged from 1 to 9 years
      of age. Small and medium-sized breeds were affected predominantly. Lesions were
      widespread and localized mainly in the brain stem, less frequently in the
      cerebrum or cerebellum. Alterations were represented by perivascular cuffs,
      parenchymal granulomas, and leptomeningeal infiltrates. Lymphocytes and
      macrophages comprised the dominant cell populations; their percentage varied
      substantially between different animals and between sections from the same
      individual. Immunohistochemically, the bulk of lymphocytes were CD3 antigen
      positive T cells, while only a few cells were CD43 and CD45R antigen-positive or
      were classified as B cells. The majority of macrophages expressed both lysozyme
      and DH82 antigen; however, some were positive for only one antigen. MHC class II
      antigen-expression, observed only within and in close proximity to the lesions,
      was found on all inflammatory cells, pericytes/endothelial cells, and microglia.
      Results were negative for canine distemper virus antigen and nucleoprotein mRNA,
      rabies virus antigen, fungi, bacteria, and protozoal agents. This
      immunomorphologic study reveals that inflammatory lesions in canine granulomatous
      meningoencephalitis consist of a heterogeneous population of MHC class II antigen
      positive macrophages and predominantly CD3 antigen-positive lymphocytes. The data
      suggest a T cell-mediated delayed-type hypersensitivity of an organ-specific
      autoimmune disease as a possible pathogenic mechanism for this unique canine
      brain lesion.

PMID- 9545135
TI  - The effects of the tremorgenic mycotoxin penitrem A on the rat cerebellum.
AB  - Within 10 minutes of intraperitoneal injection of penitrem A (3 mg/kg), rats
      develop severe generalized tremors and ataxia that persist for up to 48 hours.
      These are accompanied by a three- to fourfold increase in cerebellar cortical
      blood flow. Mitochondrial swelling occurs in cerebellar stellate and basket cells
      within 30 minutes of dosing and persists for more than 12 hours without leading
      to cell death. From 2 hours, Purkinje cell dendrites show early cytoplasmic
      condensation accompanied by fine vacuolation of smooth endoplasmic reticulum and
      enlargement of perikaryal mitochondria. From 6 hours, many Purkinje cells develop
      intense cytoplasmic condensation with eosinophilia that resembles "ischemic cell
      change," and from 12 hours, many other Purkinje cells show marked watery
      swelling. Astrocytes begin to swell from 0.5 hours after injection and show
      hypertrophy of organelles from 6 hours. Also from 6 hours onward, discrete foci
      of necrosis appear in the granule cell layer, while permeability of overlying
      meningeal vessels to horseradish peroxidase becomes evident at 8 hours. All
      changes are more severe in vermis and paravermis. Despite widespread loss of
      Purkinje cells, the animals' behavior becomes almost normal within a week. While
      tremor occurs with doses of 1.5 and 0.5 mg/kg, cellular damage is minimal. The
      tremor mechanism differs from that of harmaline since destruction of inferior
      olivary nuclei abolishes neither the tremor response to penitrem A nor the
      cellular damage. No morphological changes are found in other brain regions. The
      affinities of penitrem A for high-conductance calcium-dependent potassium
      channels and for gamma-aminobutyric acid receptors with the probability of
      resultant excitotoxity are considered to be important underlying factors for
      these changes.

PMID- 9545136
TI  - Primitive neuroectodermal tumor in a two-month-old black and white Colobus
      monkey.
AB  - A 2-month-old male black and white Colobus monkey (Colobus guereza kikuyuensis)
      was euthanatized because of progressive physical deterioration, rear limb
      paralysis, lymphadenopathy, and the presence of facial and retroperitoneal lumbar
      masses. At necropsy, soft white masses were present in and around lumbar
      vertebrae, the subcutis of the face, multiple lymph nodes, and the fourth
      ventricle of the brain. Histologic and immunohistochemical analysis of these
      masses revealed a primitive neoplasm with both neuronal and glial
      differentiation, consistent with a primitive neuroectodermal tumor (PNET) with
      bipotential differentiation. The extracranial tumors were synaptophysin (SYN)
      positive, glial fibrillary acidic protein (GFAP)-negative, and neurofilament
      protein (NFP)-negative, while the intracranial tumor was SYN-positive, GFAP
      positive, and NFP-negative.

PMID- 9545137
TI  - Macroscopic and microscopic characterization of a uriniferous perirenal
      pseudocyst in a Domestic Short Hair cat.
AB  - The macroscopic and microscopic features of a uriniferous perirenal pseudocyst in
      a castrated male 12-year-old American Domestic Short Hair cat are characterized.
      The development in humans and animals of a perirenal pseudocyst due to the
      accumulation of urine, lymph, or blood is discussed. In the presented case,
      microscopic evidence suggests that the pseudocyst developed following formation
      of a split in the kidney capsule. Emphasis is placed on the development of
      uriniferous pseudocysts and three proposed criteria for their development:
      trauma, abnormal openings that allow extravasation of urine, or urethral
      obstruction.

PMID- 9545138
TI  - Generalized AA-amyloidosis in Siberian tigers (Panthera tigris altaica) with
      predominant renal medullary amyloid deposition.
AB  - Generalized amyloidosis with predominant renal medullary amyloid deposition was
      found in four closely related Siberian tigers (Panthera tigris altaica) suffering
      from end stage kidney diseases. Only minimal to mild amounts of amyloid were
      deposited in various organs outside the kidneys with individually variable organ
      involvement. The Congo red staining affinity of amyloid deposits was sensitive to
      potassium permanganate oxidation. The deposits were further characterized as
      being of the amyloid-A (AA) type by immunohistochemistry using the mouse
      monoclonal antibody mc4 directed against a conserved region of the human AA
      protein. A combination of immunohistochemistry and Congo red staining was much
      more sensitive for the diagnosis of amyloid deposits than Congo red staining
      alone. With this combination, even minimal amyloid deposits were detected that
      had been missed in the first reading using Congo-red-stained slides alone. Since
      no common primary cause was identified, the amyloidosis was classified as
      idiopathic generalized AA-amyloidosis with a potential familial predisposition.

PMID- 9545139
TI  - Primary vascular neoplasms of lymph nodes in the dog.
AB  - Primary vascular neoplasms of lymph nodes are rare, and appear not to have
      previously been reported in domestic animals. This report describes hemangiomas
      and a lymphangioma in lymph nodes of aged Beagle dogs. Eight hemangiomas (4.8%)
      and one lymphangioma were present in 165 examined popliteal lymph nodes, and one
      hemangioma occurred in a hepatic lymph node. The hemangiomas were cavernous and
      benign.

PMID- 9545140
TI  - Polycystic kidney and liver disease in two related West Highland White Terrier
      litters.
AB  - Polycystic kidney and liver disease was present in four of six female and three
      of five male offspring born in two matings between the same pair of West Highland
      White Terriers. Clinical signs were apparent and serum biochemistry analysis
      consistent with liver failure was evident by 5 weeks of age. Affected pups were
      euthanatized because of their disease. Renal cysts were confirmed to be of
      collecting duct origin by Dolichos bifluros agglutinin lectin histochemistry, and
      hepatic cysts were of biliary origin. The clinically unaffected parents were
      related through multiple common ancestors, and there were no reports of similar
      disease in related dogs. An autosomal recessive mode of inheritance is therefore
      suggested. This is the first report of polycystic kidney and liver disease in the
      West Highland White Terrier. The features of the disease in these pups are
      similar to those of autosomal recessive polycystic kidney disease (ARPKD) in
      humans. The West Highland White Terrier may therefore be a potential animal model
      for ARPKD.

PMID- 9545141
TI  - Current management of human bites.
AB  - Human bites should be considered dangerous injuries with potentially serious
      complications. Their characteristics vary from an uninfected abrasion to a
      serious infection such as cellulitis or osteomyelitis. An estimated 10% of the
      injuries become infected; suspected pathogens include oral and skin flora.
      Management consists of history and examination, wound care, surgical intervention
      if necessary, assessment of risk of disease transmission, and appropriate
      antibiotic prophylaxis or treatment. The best choice for oral or intravenous
      antibiotic therapy remains the combination of a beta-lactam antibiotic with a
      beta-lactamase inhibitor. Among the most serious human bites are clenched fist
      injuries, which often require surgical intervention and intravenous antibiotic
      therapy.

PMID- 9545142
TI  - Antiepileptic drug withdrawal--a good idea?
AB  - Patients who are seizure free for 2 years or more are candidates for
      antiepileptic drug (AED) withdrawal. A MEDLINE search of the English language
      literature from 1980-1996 was performed to identify articles dealing with AED
      withdrawal in both adults and children. Factors examined included advantages and
      disadvantages of withdrawal, risks of relapse, prognostic factors of outcome, and
      methods of withdrawal. Advantages include psychosocial benefits, cost savings
      (direct drug costs, indirect monitoring costs), and avoidance of adverse effects
      and toxicity. The benefits must be balanced against the risks and impact of
      seizure relapse, which are different for each individual patient. A review of the
      prognostic factors that influence the risk of relapse will aid clinicians in
      determining appropriate candidates for AED withdrawal.

PMID- 9545143
TI  - Statins in the prevention of coronary heart disease.
AB  - Although epidemiologic studies proved that a causal relationship exists between
      elevated serum cholesterol levels and coronary heart disease, it is only recently
      that cholesterol-lowering strategies have shown significant reductions in total
      mortality. In the last few years, three landmark coronary artery disease
      reduction trials with HMG-coenzyme A reductase inhibitors (statins) showed
      significant reductions in coronary heart disease and mortality. Statins have
      beneficial effects on coronary heart disease and overall mortality in primary and
      secondary prevention, including in women and the elderly. Angiographic studies
      reveal the potential mechanisms through which statins exert their clinical
      benefits.

PMID- 9545144
TI  - The association between cryptococcal variety and immunocompetent and
      immunocompromised hosts.
AB  - The varieties of Cryptococcus neoformans serotypes are neoformans and gattii.
      Data suggest an association between cryptococcal variety and host immune status.
      In addition, the two varieties differ in their epidemiology and pathogenicity.
      Furthermore, symptoms, outcome, and response of cryptococcosis to antifungal
      therapy may vary. The two varieties also differ in immune-modulating effects.
      Sparse clinical data suggest var. gattii is more virulent and may be more
      recalcitrant to antifungal therapy. Also, its infections produce more sequelae. A
      better understanding of how cryptococcal variety influences the clinical course
      and response to the treatment of cryptococcosis is needed. Clinicians should be
      aware of the association, especially in patients with refractory disease. It may
      be useful to type the isolate to the variety level and administer prolonged
      antifungal therapy.

PMID- 9545145
TI  - Low-molecular-weight heparins in coronary arterial thrombus disease: a review of
      the literature.
AB  - Popularity of low-molecular-weight heparins (LMWH) continues to grow. Clinical
      trials established their efficacy for various venous thromboembolic disease
      states. Their use in arterial disorders is also becoming widespread.
      Unfortunately, clinical trials in this population subgroup are either lacking or
      show little or no benefit of LMWH. Specifically, they appear to offer no benefit
      over antiplatelet agents, such as aspirin and ticlopidine, after percutaneous
      transluminal coronary angioplasty. Conversely, they may have a role in the
      management of unstable angina. At this time, however, their efficacy appears
      equivalent only to therapeutic dosages of unfractionated heparin.

PMID- 9545147
TI  - Cyclosporine trough concentrations in predicting allograft rejection and renal
      toxicity up to 12 months after renal transplantation.
AB  - STUDY OBJECTIVE: To evaluate the utility of cyclosporine (CsA) trough
      concentrations as a monitoring tool for acute graft rejections and CsA
      nephrotoxicity. DESIGN: Retrospective chart review. SETTING: University
      affiliated teaching hospital. PATIENTS: One hundred thirty-seven adults who had
      undergone kidney transplantation. MEASUREMENTS AND MAIN RESULTS: Clinical data
      extracted from the charts were CsA dosage, CsA trough levels (whole blood, HPLC
      method), biopsy findings to confirm acute rejections, and serum creatine to
      determine clearance by the Jelliffe method. Data were collected at up to 1 month,
      between 1 month and 3 months, and between 3 and 12 months after transplantation.
      For each time period, receiver's operating characteristics curves were generated
      to identify the optimum CsA concentration for avoiding acute rejection and CsA
      nephrotoxicity. At up to 1 month, the CsA therapeutic response threshold was 182
      ng/ml (sensitivity 69%, specificity 84%, p<0.0001) and toxicity threshold for CsA
      nephrotoxicity was 204 ng/ml (sensitivity 89%, specificity 56%, p<0.0001).
      Between 1 month and 3 months, the respective figures were 175 ng/ml (sensitivity
      58%, specificity 89%, p<0.0002) and 189 ng/ml (sensitivity 87%, specificity 65%,
      p<0.0001). Between 3 and 12 months, the CsA therapeutic response threshold
      decreased to 135 ng/ml (sensitivity 56%, specificity 40%, p>0.1) and the toxicity
      threshold for CsA nephrotoxicity remained relatively static at 204 ng/ml
      (sensitivity 100%, specificity 14%, p<0.0001). CONCLUSION: Early in CsA therapy
      it is essential to prevent graft rejection. Drug concentrations exceeding
      approximately 182 ng/ml threshold accomplish this goal. Later, successful therapy
      demands that CsA nephrotoxicity be avoided. This goal is accomplished by not
      exceeding a CsA concentration of 204 ng/ml.

PMID- 9545146
TI  - Population pharmacokinetics of carbamazepine in adults with epilepsy.
AB  - STUDY OBJECTIVE: To conduct a population pharmacokinetic analysis of
      carbamazepine (CBZ). DESIGN: Retrospective chart review. SETTING: Ambulatory
      neurology clinics at three medical centers. PATIENTS: Patients diagnosed with
      epilepsy from 1991-1995. The index set included 829 adults receiving CBZ. A
      separate validation set consisted of 50 patients. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Final regression equations were apparent oral
      clearance (Cl/F) (L/hr) = (0.0134 x TBW + 3.58), x 1.42 if receiving phenytoin
      only; x 1.17 if receiving phenobarbital or felbamate; x 1.62 if receiving
      phenytoin and phenobarbital or felbamate; x 0.749 if age > or = 70 years;
      apparent volume of distribution (Vd/F) (L) = 1.97 x total body weight; absorption
      rate constant [hr(-1)] = 0.441. Interindividual variability in Cl/F and Vd/F was
      26% and 82%, respectively. Residual variability was 1.8 mg/L. Predictive
      performance analysis of the validation set provided a mean prediction error of
      0.6 mg/L and median absolute error of 2.4 mg/L. CONCLUSIONS: These routinely
      collected data provided quantitative estimates of changes in CBZ Cl/F due to
      comedication and an age-related decrease in Cl/F The derived regression equations
      reasonably predicted concentrations in a separate validation set.

PMID- 9545148
TI  - Relative bioavailability of ondansetron 8-mg oral tablets versus two
      extemporaneous 16-mg suppositories: formulation and gender differences.
AB  - STUDY OBJECTIVE: To compare the relative bioavailability of two 16-mg
      extemporaneously prepared suppository formulations with that of an 8-mg
      commercially available oral tablet. DESIGN: Prospective, crossover
      bioavailability study. SETTING: Inpatient clinical research center. SUBJECTS:
      Sixteen young, nonsmoking, healthy volunteers. INTERVENTIONS: Blood samples were
      obtained 24 and 48 hours after administration of an 8-mg oral ondansetron tablet
      and 16-mg suppository, respectively. Two 16-mg suppository formulations were
      compounded using commercially available Fattibase and Polybase. MEASUREMENTS AND
      MAIN RESULTS: Ondansetron was well absorbed by both routes of administration. The
      following pharmacokinetic parameters (mean+/-SEM) were obtained for the 8-mg
      tablet, 16-mg Fattibase suppository, and 16-mg Polybase suppository,
      respectively: area under the curve (AUC) in men 154.2+/-21.77, 253.4+/-72.3,
      304.8+/-62.2 ng x hr/ml; AUC in women 353.6+/-32.7, 561.6+/-103.6, and 768.7+/
      117.9 ng x hr/ml; maximum concentration (Cmax) in men 45.5+/-7.0, 40.6+/-10.4,
      and 51.2+/-6.7 ng/ml; Cmax in women 51.4+/-.8, 47.1+/-3.9, and 82.9+/-6.6 ng/ml.
      Times to Cmax (Tmax; mean+/-SEM) for men were 1.5+/-0.3, 4.4+/-0.5, and 2.9+/-0.3
      hours; Tmax for women were 1.8+/-0.3, 4.1+/-0.4, and 4.4+/-0.6 hours for the
      three formulations, respectively. Women had a consistently higher AUC for all
      three formulations than men (p<0.05). CONCLUSION: With the exception of the 16-mg
      Polybase formulation in women, the two suppositories closely approximated the
      pharmacokinetics of the 8-mg oral tablet. These results suggest that gender may
      be a significant factor in ondansetron's disposition.

PMID- 9545149
TI  - Food interaction and steady-state pharmacokinetics of itraconazole oral solution
      in healthy volunteers.
AB  - STUDY OBJECTIVES: To evaluate the effect of food on the bioavailability of
      itraconazole (ITR) hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solution under
      multiple-dose to steady-state conditions, and to determine the pharmacokinetics
      of ITR solution at steady state. DESIGN: Open-label, randomized, multiple-dose,
      crossover study SETTING: University-affiliated health center. PATIENTS: Thirty
      healthy men randomized to one of two treatment sequences (fasted-fed, fed
      fasted). INTERVENTIONS: Subjects were either fasted or fed a standard breakfast
      before receiving ITR oral solution 200 mg once/day for 15 days. Crossover phases
      were separated by a 4-week washout period. MEASUREMENTS AND MAIN RESULTS: On day
      1, blood samples were collected before the dose (time zero) and 0.5, 1, 2, 3, 4,
      5, 6, 8, 12, and 24 hours after the dose. Trough samples were obtained before the
      dose on days 4, 7, 12, 13, and 14. On day 15, samples were obtained at the same
      times as day 1, and at 36, 48, 72, 96, 168, 240, and 360 hours. Samples were
      analyzed by high-performance liquid chromatography for ITR and its major
      metabolite hydroxyitraconazole (OH-ITR). Urine was collected on days 1 and 15
      before and 0-8 and 8-24 hours after the dose; HP-beta-CD was measured by size
      exclusion chromatography. Mean bioavailabilities of ITR and OH-ITR were 43% and
      38% higher, respectively, when ITR solution was taken as a single dose under
      fasted conditions. With multiple dosing, steady state was achieved by day 14. At
      steady state, mean bioavailabilities were 29% and 17% higher, respectively, in
      the fasted state; terminal half-life was similar under fasted and fed conditions
      (mean 39.8 and 37.5 hrs for ITR, respectively; 27.3 and 26.2 hrs for OH-ITR,
      respectively). HP-beta-CD was eliminated almost exclusively in urine. CONCLUSION:
      The bioavailability of ITR and OH-ITR is enhanced when ITR oral solution is given
      in the fasted state; this was true for both single and multiple dosing to steady
      state.

PMID- 9545150
TI  - 1995 National Clinical Pharmacy Services Study.
AB  - To determine the extent of hospital-based clinical pharmacy services in 1995, we
      surveyed 1109 United States acute care, general, medical-surgical, and pediatric
      hospitals with 50 or more licensed beds. Fifteen clinical pharmacy services were
      assessed to determine pharmacists' specific patient care responsibilities. The
      percentage of hospitals offering services grew between 1992 and 1995:
      pharmacokinetic consultations (16% increase), drug therapy protocol management
      (15%), drug therapy monitoring (8%), drug counseling (13%), and parenteral
      enteral nutrition team (6%). All other services increased 0-5%. Pharmacists
      conducted clinical research in 14% of hospitals, averaging 6.3+/-22.1
      protocols/department annually; total budget $96,219+/-$262,026. Patient-focused
      care predominated in 20% of hospitals, although most pharmacists reported to
      directors of pharmacy through traditional pharmacy department channels. Clinical
      pharmacy services continue to expand, with pharmacists providing higher-level
      direct patient care activities related to drug therapy management and monitoring.

PMID- 9545152
TI  - Impact of patient knowledge, patient-pharmacist relationship, and drug
      perceptions on adverse drug therapy outcomes.
AB  - The purpose of this project was to determine the relationship between adverse
      drug outcomes and knowledge of drugs, quality of a counseling relationship, and
      perceptions about drugs in an ambulatory clinic population. The presence of these
      three factors and other indicators of adverse outcomes were identified through a
      structured interview of 78 patients. Medical records were reviewed 3, 6, and 12
      months after the initial interview to determine the presence of adverse drug
      outcomes. Four outcomes-hospitalizations, unscheduled clinic visits, emergency
      room visits, and changes in drug regimen-were assessed and categorized according
      to drug-related problem. Demographics of the group were recorded. Responses to
      the interview were analyzed to determine differences in counseling relationships
      between pharmacists and other health professionals. Logistic regression analysis
      was performed to determine the influence of independent variables on outcome.
      Relative risks for developing adverse outcomes given the presence of certain
      independent variables were calculated for significant associations. Significant
      relationships between predictor variables and adverse drug outcomes were
      identified for the following independent variables: female gender (RR = 5.2, CI
      1.11, 24.31), three or more diseases (RR = 3.3, CI 1.13, 9.75), more drug
      knowledge and better perceptions (RR = 0.29, CI 0.10, 0.84), perception of no or
      low drug interference (RR = 0.18, CI 0.044, 0.745), and inadequate data
      collection by nurses and physicians as perceived by the patient (RR = 3.08, CI
      1.09, 8.70). More knowledge and better perceptions about drugs were associated
      with a reduced risk of therapy changes due to drug-related problems. No
      association was found between the quality of the pharmacist-patient counseling
      relationship and adverse drug outcomes.

PMID- 9545151
TI  - The cost-effectiveness of a clinical pharmacist intervention among elderly
      outpatients.
AB  - We estimated the cost and cost-effectiveness of a clinical pharmacist
      intervention known to improve the appropriateness of drug prescribing. Elderly
      veteran outpatients prescribed at least five drugs were randomized to an
      intervention (105 patients) or control (103) group and followed for 1 year. The
      intervention pharmacist provided advice to patients and their physicians during
      all general medicine visits. Mean fixed and variable costs/intervention patient
      were $36 and $84, respectively Health services use and costs were comparable
      between groups. Intervention costs ranged from $7.50-30/patient/unit change in
      drug appropriateness. The cost to improve the appropriateness of drug prescribing
      is thus relatively low.

PMID- 9545154
TI  - Rifampin, a useful drug for nonmycobacterial infections.
AB  - Rifampin has clinical efficacy against a wide variety of organisms, including
      Staphylococcus aureus, Legionella pneumophila, group A Streptococcus, Brucella
      sp, Haemophilus influenzae, and Neisseria meningitidis, as well as in vitro
      activity against penicillin-resistant Streptococcus pneumoniae, Neisseria
      gonorrhoeae, Chlamydia trachomatis, Haemophilus ducreyi, and many gram-negative
      rods. Rifampin is a useful drug for several types of bacterial infections because
      of its broad spectrum of activity, excellent tissue penetration, and low side
      effect profile. In combination with other antibiotics, it may be effective when
      conventional therapies are not.

PMID- 9545153
TI  - Cyclosporine-induced beta-adrenergic receptor down-regulation in bovine pulmonary
      artery smooth muscle cells: a pilot study.
AB  - We attempted to determine the effects of cyclosporine on beta-adrenergic
      receptors in bovine pulmonary artery smooth muscle cells. Bovine pulmonary artery
      smooth muscle cells were exposed to cyclosporine at a concentration of 100 ng/ml
      in culture media for 5 days, and control bovine pulmonary artery smooth muscle
      cells were exposed to only culture media for the same 5-day period. Beta
      adrenergic receptors were measured as total binding capacity (Bmax) by nonlinear
      least squares fit of the specific binding curve. In a separate experiment beta1-
      versus beta2-adrenergic receptor subtypes were identified by computer modeling
      (LIGAND) of 17-19 point CGP20712A-125ICYP competition curves. Cyclosporine
      significantly (p=0.02) decreased bovine pulmonary artery smooth muscle beta
      adrenergic receptor density by 54%+/-7%. The Bmax for control versus treated
      cells was 38.9+/-18 versus 17.7+/-12 fmol/mg protein, respectively. Subtype
      determination of beta-receptors revealed 70% or more beta2- and 30% or less beta1
      adrenergic receptors. Cyclosporine caused a 54% reduction in overall beta
      adrenergic receptor density in bovine pulmonary artery smooth muscle cells. The
      reduction in Bmax is suspected not to be a result of selective down-regulation of
      beta1-adrenergic receptors alone. We believe that cyclosporine may also
      contribute to a decrease in beta2-adrenergic receptors.

PMID- 9545155
TI  - Patient recall of therapeutic paralysis in a surgical critical care unit.
AB  - STUDY OBJECTIVE: To investigate patient recall of therapeutic paralysis (TP) in a
      surgical critical care unit. DESIGN: Prospectively applied structured interview
      of patients undergoing TP over 18 months. SETTING: Surgical critical care unit
      with 27 beds at a tertiary care university teaching hospital. PATIENTS: Forty
      patients admitted for postoperative care after coronary artery bypass graft
      surgery, trauma, or gastrointestinal surgery. INTERVENTIONS: Patients received TP
      and concurrent sedation with benzodiazepines, propofol, and narcotics.
      MEASUREMENTS AND MAIN RESULTS: After the end of TP patients were asked to recall
      the experience, and their responses were ranked on a four-point ordinal scale.
      Four of 11 patients recalled mostly negative events and experiences with TP, such
      as sleeplessness, discomfort, pain, anxiety, and inconsistent caregiver
      communication. All patients with recall experienced fear, anxiety, and
      sleeplessness. Single-drug therapy with propofol and inadequate benzodiazepine
      dosing were linked to patient recall. CONCLUSIONS: Patient recollection from TP
      may be more common than appreciated and is generally unpleasant. Adequate dosing
      with benzodiazepines and narcotics is warranted to prevent recall and discomfort.

PMID- 9545156
TI  - Circadian variations in the pharmacokinetics of a new microemulsion formulation
      of cyclosporine in cardiac transplant recipients.
AB  - We attempted to characterize circadian variations in pharmacokinetic parameters
      of a new formulation of cyclosporine (CsA) in nine cardiac allograft recipients.
      A secondary objective was to determine the sampling time that correlated best
      with exposure of patients to the drug. This was a two-period study with each
      period lasting 12 hours. All patients received two equal doses of a new
      microemulsion of CsA 12 hours apart. Blood samples to measure drug levels were
      obtained at administration and 1, 2, 3, 4, 6, 9, and 12 hours after each dose. We
      found no statistically significant difference in pharmacokinetic parameters
      (areas under the curve, minimum blood concentration, oral clearance) measured
      during the day and during the night. However, maximum blood concentrations during
      the day were 30% higher than those at night (p<0.05). We found a good correlation
      between minimum concentrations in the morning and overall exposure of patients to
      CsA (r=0.89). This new microemulsion appears to have few circadian variations of
      blood concentrations in cardiac transplant recipients. The clinical significance
      of higher maximum blood concentration during daytime remains to be elucidated.
      Our results support the most widely accepted method for monitoring CsA, which is
      based on minimum concentrations in the morning.

PMID- 9545157
TI  - Effect of pharmacokinetic sampling methods on aminoglycoside dosing in critically
      ill surgery patients.
AB  - We compared pharmacokinetic parameters derived from three aminoglycoside serum
      concentration sampling methods and evaluated their effects on recommended
      aminoglycoside dosing regimens in 60 critically ill surgery patients. Patients
      had presumed or documented gram-negative sepsis, and had at least 4
      aminoglycoside serum concentrations measured. We used a one-compartment model for
      peak and trough, 3-point series, and 4-point series sampling methods. Dosing
      regimens were calculated for each patient based on values derived from each
      method. We found differences in regimens for nearly 50% of patients if either 4-
      or 3-point series sampling was used to calculate the recommended dosage rather
      than peak and trough sampling. However, the 3-point method required a clinically
      significant change in regimen in only 12% of patients compared with 4-point
      sampling. The variability of all values derived from 3-point sampling were well
      accounted for by the 4-point method (r2 > 0.80). In addition, we noted
      significantly greater relative precision for 3-point sampling than peak and
      trough sampling for estimates of clearance, elimination rate, recommended daily
      dosage, and recommended dosing frequency. We recommend three optimally timed
      samples be drawn instead of peak and trough levels in dosing aminoglycosides in
      critically ill surgery patients.

PMID- 9545158
TI  - Nefazodone: single versus twice daily dose.
AB  - This pilot study involved six men with major depression treated with nefazodone
      dosed either twice/day or once/day at bedtime. Depression was rated before
      nefazodone therapy and at 4 weeks by the self-report version of the Hamilton
      Depression Rating Scale. A simple 10-cm visual analog side effect scale for
      daytime drowsiness was completed at the latter time. Dosages of nefazodone were
      at least 400 mg/day. The results suggest that nefazodone given once/day at
      bedtime may be as effective as the currently accepted twice/day regimen, with
      less daytime drowsiness.

PMID- 9545159
TI  - Prolongation of the QT interval related to cisapride-diltiazem interaction.
AB  - Cisapride, a cytochrome P450 3A4 (CYP3A4) substrate, is widely prescribed for the
      treatment of gastrointestinal motility disorders. Prolongation of QT interval,
      torsades de pointes, and sudden cardiac death have been reported after
      concomitant administration with erythromycin or azole antifungal agents, but not
      with other CYP3A4 inhibitors. A possible drug interaction occurred in a 45-year
      old woman who was taking cisapride for gastroesophageal reflux disorder and
      diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. The
      patient was in near syncope and had QT-interval prolongation. After discontinuing
      cisapride, the QT interval returned to normal and symptoms did not recur. We
      suggest that caution be taken when cisapride is prescribed with any potent
      inhibitor of CYP3A4, including diltiazem.

PMID- 9545160
TI  - Delayed elevation of international normalized ratio with concurrent
      clarithromycin and warfarin therapy.
AB  - Clarithromycin is rarely reported to cause disturbances in anticoagulation.
      Theoretically, clarithromycin administered concurrently with warfarin could
      result in enhanced anticoagulation, since many properties of clarithromycin are
      similar to those of erythromycin, which interacts with warfarin. A search of the
      National Library of Medicine produced no published reports of an interaction
      between the drugs. Erythromycin competitively inhibits hepatic metabolism of
      warfarin, specifically the R-warfarin enantiomer, by the cytochrome P450 3A3 and
      3A4 pathways, resulting in increased prothrombin time and international
      normalized ratio (INR). Two men, age 61 and 70 years, who received stable
      warfarin regimens, experienced supratherapeutic elevations in prothrombin time
      (98.4 and 26.8 sec) and INR (90.3 and 5.6), respectively. While taking warfarin,
      both patients experienced dramatically increased anticoagulation effects 5 days
      after starting clarithromycin for atypical pneumonia. They were similarly managed
      for overanticoagulation by discontinuing clarithromycin, holding warfarin, and
      receiving intravenous phytonadione. Neither man suffered from medical
      complications related to anticoagulation. Until clear documentation of the exact
      mechanism and temporal relationship of this interaction is known, patients
      receiving warfarin who require the concurrent clarithromycin should have
      prothrombin time and INR closely monitored.

PMID- 9545161
TI  - Fatal toxic epidermal necrolysis related to lamotrigine administration.
AB  - Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe
      life-threatening dermatologic conditions. To date, eight cases of TEN and one of
      SJS related to lamotrigine administration have been reported in the literature.
      Most patients were also taking concomitant valproic acid. It was hypothesized
      that valproic acid may interfere with glucuronidation of lamotrigine, leading to
      increased serum lamotrigine levels, or perhaps alter the drug's metabolism,
      resulting in accumulation of a toxic intermediate metabolite. Ultimately, this
      may possibly predispose a patient to increased dermatologic reactions, including
      TEN. A 54-year-old man developed TEN 4 weeks after beginning lamotrigine for
      complex partial seizures related to a glioblastoma multiforme brain tumor. The
      patient had also been taking concomitant allopurinol and captopril for more than
      4 years with no complications, and valproic acid 3 months before the cutaneous
      event. Despite aggressive intensive care management, the patient died 17 days
      from the onset of symptoms due to multiple organ failure. Administration of
      lamotrigine, especially in combination with valproic acid, may lead to the
      development of TEN.

PMID- 9545162
TI  - Serotonin syndrome secondary to phenelzine-venlafaxine interaction.
AB  - A 44-year-old woman accidentally ingested phenelzine along with venlafaxine.
      Thirty minutes after the ingestion the woman began to feel nauseous and anxious.
      Approximately 45 minutes later a friend noted that the woman had lower extremity
      shaking and increasingly rapid respirations. The friend brought the woman to the
      emergency department and she was subsequently diagnosed with serotonin syndrome.
      Serotonin syndrome is usually precipitated by combinations of serotonin
      potentiating agents and can lead to devastating outcomes. When using combinations
      of drugs that elevate serotonin levels in the central nervous system, the
      possibility of serotonin syndrome should be considered.

PMID- 9545163
TI  - Famotidine-associated mental status changes.
AB  - A 77-year-old man who had taken ranitidine for several years for dyspepsia was
      prescribed alternative therapy with famotidine 20 mg twice/day. He subsequently
      developed mental status changes, with confusion, disorientation, and nightmares.
      The symptoms dissipated after he discontinued famotidine for 2 days. He
      rechallenged himself and experienced return of the symptoms shortly thereafter,
      with additional visual hallucinations. His therapy was changed to lansoprazole,
      and his symptoms again disappeared and have not recurred. Case reports of central
      nervous system effects with other histamine2 antagonists have been published.
      Eight cases occurred with famotidine, all of which were in hospitalized patients
      receiving intravenous famotidine. We believe this is the first report of mental
      status changes in an ambulatory patient taking oral famotidine. The elderly may
      be particularly susceptible to such changes.

PMID- 9545164
TI  - Subcutaneous enoxaparin for outpatient anticoagulation therapy in a patient with
      an aortic valve replacement.
AB  - Low-molecular-weight heparins have been administered for a variety of clinical
      conditions. A patient with a mechanical aortic valve replacement patient
      underwent elective transurethral prostatectomy. Anticoagulation was managed with
      unfractionated heparin immediately preoperatively and postoperatively. Warfarin
      was begun on postoperative day 1. The patient had a prolonged hospitalization due
      to subtherapeutic international normalized ratios (INR) despite warfarin
      administration. Because he intended to leave the hospital against medical advice
      before therapeutic INR was achieved, enoxaparin 1 mg/kg subcutaneously every 12
      hours was prescribed to provide anticoagulation, facilitating discharge and
      improving the patient's quality of life. Enoxaparin was associated with an
      approximate saving of $4500 over warfarin. The only adverse event reported was
      bruising at the injection site.

PMID- 9545165
TI  - Octreotide-induced bradycardia.
AB  - Because of deleterious hemodynamic effects of octreotide in a nonacromegalic
      patient with a pancreatic fistula, we conducted a MEDLINE search of English
      language journal articles to extract information on this complication of
      octreotide or somatostatin therapy. Few data are available regarding patients
      with disease states other than acromegaly. We believe octreotide should be
      considered when determining the cause of bradycardia.

PMID- 9545166
TI  - The strategic plan of the American College of Clinical Pharmacy 1998-2000.

PMID- 9545167
TI  - Clinical utility research: an introduction.
AB  - Clinical utility research is concerned with how one develops knowledge that can
      be directly used for improving clinical practice. Some have referred to this
      domain as "effectiveness" research, but clinical utility implies much more than
      clinical effectiveness. It also addresses issues of access, transferability,
      sample specificity, and the uniqueness of each human condition. This special
      series of papers describe several research programs that have been conducted in
      applied settings and that illustrate research on clinical utility. These
      descriptions are modestly representative of the wide applicability of research
      methods that address the uniqueness of each setting and population and the nature
      of findings that can be used to guide clinical practice. The papers bridge
      cultures, countries, settings, and problems. They illustrate some of the
      advantages of, and some of the knowledge to be gained from conducting controlled
      research in settings that are devoted to clinical service.

PMID- 9545168
TI  - Diagnosis and treatment of depression in primary medical care practice: the
      application of research findings to clinical practice.
AB  - Approximately 50% of persons experiencing clinical depression seek help for this
      disorder from their primary care physician. This pattern of help-seeking has
      stimulated interest in providing appropriate treatment for depressed primary
      medical care patients. While the efficacy of both psychotherapy and
      pharmacotherapy for depression have been demonstrated in the mental health
      specialty sector, current research endeavors to establish the effectiveness of
      such treatments when provided to primary medical care patients. We review and
      discuss the clinical, practical, and methodological issues pertaining to the
      transfer of depression research to routine primary care practice. Possible
      directions for future research which will inform the continued applicability of
      research findings to routine practice are discussed.

PMID- 9545169
TI  - Research in training clinics: a bridge between science and practice.
AB  - Clinics associated with psychology training programs have potential to generate
      important research data. The expectation that research be experimental in nature
      has limited the pursuit of research in training clinics. This type of efficacy
      study is not feasible in most clinics, where too much variation occurs as a
      result of training and administrative demands. Numerous process-outcome studies
      have been effectively conducted in training clinics. This article reviews some of
      these studies, identifies problems related to research in training clinics, and
      makes recommendations for the development of an enhanced research agenda for
      training clinics.

PMID- 9545170
TI  - Factors associated to outcome in psychotherapy: an effectiveness study in Puerto
      Rico.
AB  - Psychotherapy research has not received much attention among Latinos in the U.S.
      or in Latin America including Puerto Rico. The present study explores factors
      associated with the effectiveness of psychotherapy with a sample of Puerto
      Ricans. Seventy-nine persons who received psychotherapy participated in a study
      aimed at evaluating the process and outcome of psychotherapy. Participants
      completed a questionnaire on the effects of treatment on the presenting problem.
      Information from the questionnaire and other information from the clinical
      records included the BDI and the Symptom Check List-36 scores, the number of
      sessions received, etc. constituted the data set. The results show that
      symptomatic severity, age. the number of sessions, and the therapeutic alliance
      were associated with effectiveness. Also, the alliance explained 45% of the
      variance in effectiveness. The results suggest that the therapeutic alliance
      merits further study in psychotherapy research and in clinical training.

PMID- 9545171
TI  - The research program at AIGLE.
AB  - The purpose of this work is to present the research program of a Clinical Center,
      the AIGLE Foundation in Buenos Aires, Argentina. It describes the potentialities
      and advantages of research in this context. It also describes the institute, the
      types of patients treated and its professional staff. The program covers four
      areas: determining the demand for psychotherapeutic care in the population at
      large, studying the conditions making participation in community mental health
      possible, analyzing and follow-up on the outcomes and studying the personal
      styles of the therapists. Finally, this work discusses the usefulness and
      applicability of these results for clinical practice.

PMID- 9545172
TI  - From the laboratory to the hospital, adults to adolescents, and disorders to
      personality: the case of psychological reactance.
AB  - Study 1 assessed whether trait reactance in disturbed adolescents (ages 12 to 17)
      is part of the same constellation of personality variables associated with
      reactance in adults, and Study 2 examined whether reactance predicts inpatient
      treatment duration and outcomes. Correlations between reactance and MMPI-A
      variables among 76 inpatients (41 girls) showed that reactance is associated with
      oppositional, nonaffiliative, and narcissistic traits in disturbed adolescents as
      well as adults. Reactance predicted longer hospital stays among 176 adolescents
      (90 girls), and also changes in aggression, mood problems, and substance abuse
      among those in middle (n=89) but not early (n=87) adolescence. Additional
      analyses identified "typically male" and "typically female" patterns of reactance
      change relationships. The clinical significance and utility of these findings are
      discussed.

PMID- 9545173
TI  - Using feedback on patient progress to predict the outcome of psychotherapy.
AB  - The Dose-Response and Phase Models are useful for informing quality assurance
      research on the expected patterns for separate categories of outcomes in
      psychotherapy. Moreover, these models predict the sequence of change for outcomes
      that may be differentially valued by patients, therapists, stakeholders, and cost
      managers. Valid feedback on the progress of treatment is critical because
      patients, therapists, and cost managers make decisions about continuation and
      focus of treatment while psychotherapy is in progress. In this study, the focus
      is on the validity of feedback data for therapist appraisal of patient progress.
      Feedback at patient intake, in early sessions of psychotherapy, and at later
      sessions of psychotherapy is considered. Among the variables examined are patient
      and therapist agreement on severity, level of severity, evidence of
      remoralization, and evidence of symptomatic remission. Data are drawn from
      archived records of 243 psychotherapy cases conducted in several managed care
      service delivery settings. The implications of a therapist's use of feedback to
      adjust the therapeutic process in an individual case are discussed.

PMID- 9545174
TI  - Congenital muscular dystrophies: 1997 update.
AB  - The congenital muscular dystrophies (CMDs) comprise a heterogeneous group of
      muscle disorders with onset in utero or during the first year of life. Several
      forms of CMD show various types of brain involvement in addition to a muscular
      dystrophy. Two forms are defined at the molecular level: merosin deficient-CMD
      caused by mutations in the LAMA2-gene on chromosome 6q2. Fukuyama congenital
      muscular dystrophy (FCMD) is prevalent in Japan and caused by an as yet
      unidentified gene on chromosome 9q31. At least two further forms of CMD with
      brain involvement are nosologically well defined: Walker--Warburg-CMD is
      characterized by lissencephaly type 11, eye dysgenesis and muscular dystrophy.
      This autosomal recessive disorder is fatal or results in complete lack of
      development. A similar but much milder phenotype with pachygyria of the brain,
      various degrees of eye changes and milder muscular dystrophy that is compatible
      with achievement of simple motor milestones has been described under the name of
      muscle-eye-brain disease (MEB) in Finland. A number of nosologically less
      distinct forms of muscular dystrophy have been outlined such as 'pure' CMD
      without brain involvement, CMD with cerebellar hypoplasia or CMD type Ullrich
      with hyperelasticity of the distal joints. Several other CMD phenotypes are
      known, some of which are suggestive of more distinctly separate nosological
      entities due to their occurrence in siblings or due to a characteristic pattern
      of clinical, histopathological and imaging features, and await further
      clarification.

PMID- 9545175
TI  - Mechanisms of generalized absence epilepsy.
AB  - Absence seizures represent bilaterally synchronous burst-firing of an ensemble of
      reciprocally connected neuronal populations located in the thalamus and
      neocortex. Recent studies demonstrate that neurons in the reticular thalamic
      nucleus (nRt), thalamic relay neurons (RNs), and neocortical pyramidal cells
      comprise a circuit that sustains the thalamocortical oscillatory burst-firing of
      absence seizures. Recent studies have focused on three intrinsic neuronal
      mechanisms that increase the likelihood of thalamocortical oscillations. The
      first mechanism involves T-currents elicited by activating the T-type calcium
      channel, which appear to trigger sustained burst-firing of thalamic neurons
      during absence seizures. A second intrinsic mechanism is GABA B receptors which
      can elicit longstanding hyperpolarization in thalamic neurons required to 'prime'
      T-channels for sustained burst-firing. A third mechanism involves the ability of
      GABA A receptors, located on nRt neurons, to mediate recurrent inhibition.
      Enhanced activation of GABA A receptors on nRt neurons decreases the pacemaking
      capacity of these cells, therefore decreasing the likelihood of generating
      absence seizures. Cholinergic mechanisms through modulating cortical excitability
      and excitatory amino acid mediated mechanisms through depolarizing thalamic
      neurons also play a role in absence seizures.

PMID- 9545176
TI  - Reflex sympathetic dystrophy associated with deep peroneal nerve entrapment.
AB  - Reflex sympathetic dystrophy (RSD or causalgia) has been rarely reported in
      children. We now report a 10-year-old boy with RSD in whom we performed extensive
      ancillary investigations including thermography, bone scintigraphy and dermo
      echography. The clinical, laboratory and ancillary studies reported here
      highlight the profound focal acquired autonomic disturbance in this disorder. The
      patient presented a compression of the deep peroneal nerve at the inferior
      extensor retinaculum in the affected limb. Surgical decompression lead to rapid
      improvement of the patient's condition. Peripheral nerve decompression should be
      considered as a possible treatment of RSD in children, particularly those that
      are refractory to conservative maneuvers.

PMID- 9545177
TI  - Panniculitis due to potassium bromide.
AB  - Potassium bromide again is well known to be surprisingly effective in patients
      with severe myoclonic epilepsy in infants (SME). Rare side effects on the skin
      reappeared, such as the febrile nodular panniculitis (Weber-Christian syndrome).
      In 1993 we described the first three cases of necrotizing panniculitis and
      introduced the term 'halogen panniculitis'. It is a systemic disease with crops
      of subcutaneous nodules, fever, elevated sedimentation rate, hepatosplenomegalia,
      and abdominal pain. Later severe necrosis of the skin and adipose tissue may
      happen with deep ulcerations. History and course of five cases, described in this
      paper, suggest either an allergy or toxic reason. Histologic picture shows
      inflammation of adipose tissues with infiltrating lymphocytes, but lymphocyte
      transformation test (LTT) was not reliable in diagnosing the disease. Possibly,
      bromides act as a chemokine and stimulate inflammatory processes. Bromide can be
      transformed into a bromine radical/free electron pair under UV irradiation at
      228.8 nm in aqueous solution. The bromine radical may have detrimental effects on
      the tissue. However, despite some research, the origin of halogen panniculitis
      and similar diseases remains unclear.

PMID- 9545178
TI  - Neuronal nuclear antigen (NeuN): a marker of neuronal maturation in early human
      fetal nervous system.
AB  - Neuronal nuclear antigen (NeuN) immunocytochemistry was studied in 15 normal
      human fetal nervous systems of 8-24 weeks gestation and in four term neonates.
      Material was derived from products of conception or from autopsy. Antigen
      retrieval was enhanced for immunocytochemistry by microwave heating of formalin
      fixed paraffin sections. NeuN appears highly specific as a marker of neuronal
      nuclei in human fetal brain. Only rare nuclei are recognized in the germinal
      matrix. Cerebellar external granule cells are more strongly immunoreactive than
      postmigratory internal granule cells until 24 weeks gestation; by term most
      internal and only a few external granule cells are recognized by NeuN antibody.
      In the cerebrum, some reactive nuclei are demonstrated along radial glial fibers,
      particularly near the cortical plate. Within the cortical plate, only deep
      neurons (future layers 4-6) are marked at 19-22 weeks, but by 24 weeks most
      neurons in the cortical plate exhibit immunoreactivity, though at term some in
      layer 2 are still non-reactive. Some neurons fail to be recognized by NeuN at all
      ages: Cajal-Retzius cells, Purkinje cells, inferior olivary and dentate nucleus
      neurons, and sympathetic ganglion cells are examples. Despite their common origin
      in the cerebellar tubercle, basal pontine neurons are strongly reactive even
      before midgestation, hence NeuN does not predict embryonic origin. Neurons of
      dorsal root and cranial nerve ganglia are reactive even at 8 weeks. This study of
      normal fetal central nervous system provides a basis for neuropathological
      evaluation and as a prelude to applications in cerebral dysgeneses.

PMID- 9545179
TI  - Increased levels of GM2 ganglioside in fibroblasts from a patient with juvenile
      Niemann-Pick disease type C.
AB  - A 15-year-old boy was suffering from splenomegaly and a 10-year history of a
      neurologic disorder that included mental retardation, vertical supranuclear gaze
      palsy, dysarthria, ataxia, and dystonia. Bone marrow aspirates revealed foamy
      cells with storage materials which were positive with filipin staining. Cultured
      skin fibroblasts derived from the patient showed moderate loss of
      sphingomyelinase activity and the impairment of cholesterol esterification. The
      characteristic clinical presentations and typical histochemical findings of this
      patient met the diagnostic criteria of Niemann-Pick disease type C (NPC). In the
      fibroblasts from the patient, there was an accumulation of GM2 ganglioside around
      their cytoplasms. Increased levels of glycolipids. including GM2 ganglioside are
      reported in the cerebral cortex of NPC, but not in the fibroblasts. The
      fibroblasts derived from NPC may reflect the abnormal metabolism of glycolipids
      in the central nervous system of NPC.

PMID- 9545180
TI  - Neuropathological characteristics and alteration of the dopamine D2 receptor in
      hypoxic-ischemic basal ganglia necrosis.
AB  - The neuropathological characteristics and alteration of the dopamine D2 receptor
      (D2R) were investigated in 27 cases of hypoxic-ischemic basal ganglia necrosis
      (BGN) by means of neuropathological and immunohistochemical methods. Perinatal
      hypoxic-ischemic BGN manifested neuronal karyorrhexis as well as eosinophilia,
      karyorrhexis being more predominant in preterm infants and eosinophilia more
      predominant in full-term infants. Immunoreactivity to D2R was detected in the
      cytoplasm and dendrites of small and large neurons in the basal ganglia, and
      increased with neuronal maturation during the late gestational period in normal
      human basal ganglia. The number of D2R-positive neurons was smaller in all cases
      of acute BGN than that in controls, the areas of decreased D2R-positive neurons
      corresponding to the damaged regions observed on HE staining. Furthermore,
      neurons showed high expression of D2R in a few cases of remote BGN, suggesting
      some plasticity as to the recovery of D2R. Thus, the neuropathological
      characteristics of perinatal hypoxic-ischemic BGN may be related to neuronal
      maturation during different developmental stages in each region, and D2R
      development may play a role in the basal ganglia vulnerability to hypoxic
      ischemia.

PMID- 9545181
TI  - Benign partial epilepsy in infancy with complex partial seizures (Watanabe's
      syndrome): 12 non-Japanese new cases.
AB  - International epilepsy classification includes different epileptic syndromes with
      favourable outcomes in pediatric age. In addition to these, other forms probably
      exist and in various papers in international literature they are proposed as new
      entities. This article presents a survey of benign complex partial epilepsy in
      infancy, a new epileptic syndrome first proposed by Watanabe, in 1987. Our work
      represents the only description of non-Japanese cases although similar but
      familial cases had been referred by Vigevano in 1992. We present data for 12
      children (aged up to 9 years) followed over 2 years who had all the typical
      clinical features characterizing Watanabe's cases. For all of them we obtained
      EEG seizure recordings demonstrating the partial nature of their fits, arising
      from occipital or temporal regions. Interictal EEG were completely normal, both
      in waking and sleep. Evolution demonstrated benign outcome and all the children
      are seizure-free (eight of them have already stopped all medication) and all have
      normal psychomotor development.

PMID- 9545182
TI  - Severe infantile congenital myopathy with nemaline and cytoplasmic bodies: a case
      report.
AB  - A Japanese boy had marked generalized hypotonia and weakness and progressive
      respiratory failure since birth. Left biceps brachii muscle biopsy at 47 days of
      age showed marked variation in muscle fiber size, and nemaline and/or cytoplasmic
      bodies in approximately 10% of the muscle fibers. To our knowledge, the presence
      of nemaline and cytoplasmic bodies in the same muscle has not been previously
      reported. The severity of his respiratory failure and muscle weakness were
      thought to be related to muscle immaturity since there were many undifferentiated
      type 2C fibers.

PMID- 9545183
TI  - Paroxysmal tonic upgaze of childhood with ataxia: a benign transient dystonia
      with autosomal dominant inheritance.
AB  - Paroxysmal tonic upgaze of childhood with ataxia is a rare form of age related
      dystonia. Out of 12 previously reported cases, three had a clinical history of
      similar symptoms occurring in at least one first degree relative belonging to the
      same or two consecutive generations. Autosomal dominant inheritance was therefore
      hypothesized. We report on a family in which the disorder appeared in three
      consecutive generations between ages 6 and 11 months, disappearing gradually and
      spontaneously between ages 18 to 24 months. All affected individuals had normal
      neurologic development. The pedigree analysis of previously reported cases and of
      the family reported herein provides strong evidence that the disorder may be
      inherited as an autosomal dominant trait and represents a form of transient
      paroxysmal dystonia with benign long-term prognosis.

PMID- 9545184
TI  - Neuropsychological recovery from childhood moyamoya disease.
AB  - These reports describe mental recovery from childhood moyamoya disease wherein
      comprehensive and valid neuropsychological testing is administered in serial
      fashion. Two young children diagnosed with moyamoya disease underwent procedures
      to achieve bilateral revascularization. Neuropsychological studies were
      administered pre-operatively in one case and in serial fashion post-operatively
      through longer-term follow-up in both cases. Results indicated a trend of gradual
      improvements in both cases. The disease process and its postulated
      neuroanatomical and hemodynamic relationship to the psychometric findings are
      discussed.

PMID- 9545185
TI  - A case report of remarkable improvement of motor disturbances with L-dopa in a
      patient with post-diffuse axonal injury.
AB  - A 9-year-old girl with rigidospastic quadriplegia as post-traumatic sequela was
      reported. The distribution of lesions observed on a MRI implied diffuse axonal
      injury; involvement of the substantia nigra was also detected. L-Dopa
      administration was remarkably effective for relief of the rigidity. As a result,
      she became able to walk on her knees and communicate by writing letters. L-Dopa
      administration should be considered for patients who show rigidity as sequela of
      diffuse axonal injury with involvement of the substantia nigra.

PMID- 9545186
TI  - Trisomy 12p and epilepsy with myoclonic absences.
AB  - We report the case of a 6-year-2-month-old female affected by trisomy 12p
      syndrome. Seizures were typical myoclonic absences from both the clinical and EEG
      points of view. Our patient and other sporadic reports in the literature seem to
      support the hypothesis that, at least in some cases, myoclonic absences can be a
      direct or indirect effect of a chromosomopathy.

PMID- 9545187
TI  - Developmental signalling: a careful balancing act.
AB  - Embryos of arthropods and chordates are patterned along the dorso-ventral axis by
      a gradient of secreted morphogens of the Bmp4/Dpp family. This gradient now
      appears to be shaped by the opposing activities of Bmp-sequestering proteins, on
      the one hand, and Bmp-releasing metalloproteases, on the other.

PMID- 9545188
TI  - Zebrafish genetics: harnessing horizontal gene transfer.
AB  - The promiscuous spread of Tc1/mariner transposons across species implies that
      host factors are relatively unimportant for their transposition. Heterologous
      elements can integrate on expression of the corresponding transposases, an
      approach that should greatly facilitate genetic analysis in the zebrafish.

PMID- 9545189
TI  - Visual attention: controlling what we see and do.
AB  - Controlling what we see and do in complex environments depends upon the
      interaction of top-down control mechanisms located in the prefrontal cortex, on
      the one hand, and bottom-up competition between objects for limited perceptual
      resources in posterior cortical areas, on the other.

PMID- 9545190
TI  - Translation control: connecting mitogens and the ribosome.
AB  - The identification of 3-phosphoinositide-dependent kinase 1 (PDK1) as one of the
      elusive 70 kDa S6 kinase kinases has filled a gap in the signaling pathway by
      which extracellular receptors regulate translation. Will it cause us to
      reconsider the relationships between previously identified members of the
      pathway?

PMID- 9545191
TI  - Population genetics: surviving under mutation pressure.
AB  - Concern has been voiced about the survival of endangered species, and even the
      long-term prospects for humans, in the face of accumulating deleterious
      mutations. Two experiments have investigated the mutation accumulation process in
      laboratory Drosophila populations, with apparently conflicting results.

PMID- 9545193
TI  - Obesity: progress through genetic manipulation.
AB  - Transgenic mice have been produced that either lack or overproduce
      neuroregulatory substances implicated in the control of food intake and body
      weight. Are such mice useful models for understanding the underlying etiology of
      obesity in humans?

PMID- 9545192
TI  - Cancer predisposition: where's the phosphate?
AB  - Mutations in a protein phosphatase and a protein kinase cause hamartomatous
      polyposis syndromes, which are characterised by the formation of multiple benign
      polyps and an increased susceptibility to some types of cancer.

PMID- 9545194
TI  - Temporal precision of the encoding of motion information by visual interneurons.
AB  - BACKGROUND: There is much controversy about the timescale on which neurons
      process and transmit information. On the one hand, a vast amount of information
      can be processed by the nervous system if the precise timing of individual spikes
      on a millisecond timescale is important. On the other hand, neuronal responses to
      identical stimuli often vary considerably and stochastic response fluctuations
      can exceed the mean response amplitude. Here, we examined the timescale on which
      neural responses could be locked to visual motion stimuli. RESULTS: Spikes of
      motion-sensitive neurons in the visual system of the blowfly are time-locked to
      visual motion with a precision in the range of several tens of milliseconds.
      Nevertheless, different motion-sensitive neurons with largely overlapping
      receptive fields generate a large proportion of spikes almost synchronously. This
      precision is brought about by stochastic rather than by motion-induced membrane
      potential fluctuations elicited by the common peripheral input. The stochastic
      membrane-potential fluctuations contain more power at frequencies above 30-40 Hz
      than the motion-induced potential changes. A model of spike generation indicates
      that such fast membrane-potential changes are a major determinant of the precise
      timing of spikes. CONCLUSIONS: The timing of spikes in neurons of the motion
      pathway of the blowfly is controlled on a millisecond timescale by fast membrane
      potential fluctuations. Despite this precision, spikes do not lock to motion
      stimuli on this timescale because visual motion does not induce sufficiently
      rapid changes in the membrane potential.

PMID- 9545195
TI  - Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in
      living mammalian cells.
AB  - BACKGROUND: The amplification of oncogenes in cancer cells is often mediated by
      paired acentric chromatin bodies called double minute chromosomes (DMs), which
      can accumulate to a high copy number because of their autonomous replication
      during the DNA synthesis phase of the cell cycle and their subsequent uneven
      distribution to daughter cells during mitosis. The mechanisms that control DM
      segregation have been difficult to investigate, however, as the direct
      visualization of DMs in living cells has been precluded because they are far
      smaller than normal chromosomes. We have visualized DMs by developing a highly
      sensitive method for observing chromosome dynamics in living cells. RESULTS: The
      human histone H2B gene was fused to the gene encoding the green fluorescent
      protein (GFP) of Aequorea victoria and transfected into human HeLa cells to
      generate a stable line constitutively expressing H2B-GFP. The H2B-GFP fusion
      protein was incorporated into nucleosomes without affecting cell cycle
      progression. Using confocal microscopy, H2B-GFP allowed high-resolution imaging
      of both mitotic chromosomes and interphase chromatin, and the latter revealed
      various chromatin condensation states in live cells. Using H2B-GFP, we could
      directly observe DMs in living cancer cells; DMs often clustered during anaphase,
      and could form chromosomal 'bridges' between segregating daughter chromosomes.
      Cytokinesis severed DM bridges, resulting in the uneven distribution of DMs to
      daughter cells. CONCLUSIONS: The H2B-GFP system allows the high-resolution
      imaging of chromosomes, including DMs, without compromising nuclear and
      chromosomal structures and has revealed the distinctive clustering behavior of
      DMs in mitotic cells which contributes to their asymmetric distribution to
      daughter cells.

PMID- 9545196
TI  - Dissociation of the signalling and antiviral properties of SDF-1-derived small
      peptides.
AB  - BACKGROUND: The chemokine receptor CXCR4 (a receptor for the Cys-X-Cys class of
      chemokines) is a CD4-associated coreceptor for T-cell-tropic strains of human
      immunodeficiency virus 1 (HIV-1) and represents a target for antiviral therapy.
      Infection by T-tropic HIV-1 can be blocked by stromal-cell-derived factor-1 (SDF
      1), the natural ligand of CXCR4. The broad variety of cells expressing CXCR4 and
      the perturbations observed in mice deficient for SDF-1 suggest that antiviral
      compounds antagonizing the signalling activity of CXCR4 might have severe side
      effects in vivo. Compounds that interfere selectively with HIV entry and not with
      SDF-1 signalling would therefore be useful. RESULTS: A series of peptides, each
      of 13 residues, spanning the whole SDF-1alpha sequence were tested for their
      ability to block HIV-1 infection. The antiviral and signalling properties of SDF
      1 were retained by a peptide corresponding to its amino terminus. Removal of the
      first two residues resulted in an antiviral antagonist of the SDF-1-CXCR4
      signalling pathway. We prepared 234 single-substitution analogues and identified
      one antiviral analogue that had drastically reduced agonistic or antagonistic
      properties. The antiviral peptides competed with the monoclonal antibody 12G5 for
      CXCR4 binding. Their antiviral activity seems to be due to receptor occupancy
      rather than induction of receptor endocytosis. CONCLUSIONS: The amino terminus of
      the SDF-1 chemokine is sufficient for signal transduction via CXCR4 and for
      inhibition of HIV-1 entry, but these activities could be dissociated in a peptide
      analogue. This peptide represents a lead molecule for the design of low molecular
      weight antiviral drugs.

PMID- 9545197
TI  - Repair of oxidatively damaged guanine in Saccharomyces cerevisiae by an
      alternative pathway.
AB  - BACKGROUND: Transversion mutations are caused by 8-oxoguanine (OG), a DNA lesion
      produced by the spontaneous oxidation of guanine nucleotides, which mis-pairs
      with adenine during replication. Resistance to this mutagenic threat is mediated
      by the GO system, the components of which are functionally conserved in bacteria
      and mammals. To date, only one of three GO system components has been identified
      in the budding yeast Saccharomyces cerevisiae, namely the OG:C-specific
      glycosylase/lyase yOgg1. Furthermore, S. cerevisiae has been reported to contain
      a unique glycosylase/lyase activity, yOgg2, which excises OG residues opposite
      adenines. Paradoxically, according to the currently accepted model, yOgg2
      activity should increase the mutagenicity of OG lesions. Here we report the
      isolation of yOgg2 and the elucidation of its role in oxidative mutagenesis.
      RESULTS: Borohydride-dependent cross-linking using an OG-containing
      oligonucleotide substrate led to the isolation of yOgg1 and a second protein,
      Ntg1, which had previously been shown to process oxidized pyrimidines in DNA. We
      demonstrate that Ntg1 has OG-specific glycosylase/lyase activity
      indistinguishable from that of yOgg2. Targeted disruption of the NTG1 gene
      resulted in complete loss of yOgg2 activity and yeast lacking NTG1 had an
      elevated rate of A:T to C:G transversions. CONCLUSIONS: The Ntg1 and yOgg2
      activities are encoded by a single gene. We propose that yOgg2 has evolved to
      process OG:A mis-pairs that have arisen through mis-incorporation of 8-oxo-dGTP
      during replication. Thus, the GO system in S. cerevisiae is fundamentally
      distinct from that in bacteria and mammals.

PMID- 9545198
TI  - Exogenous phospholipase D generates lysophosphatidic acid and activates Ras, Rho
      and Ca2+ signaling pathways.
AB  - BACKGROUND: Phospholipase D (PLD) hydrolyzes phospholipids to generate
      phosphatidic acid (PA) and a free headgroup. PLDs occur as both intracellular and
      secreted forms; the latter can act as potent virulence factors. Exogenous PLD has
      growth-factor-like properties, in that it induces proto-oncogene transcription,
      mitogenesis and cytoskeletal changes in target cells. The underlying mechanism is
      unknown, although it is generally assumed that PLD action is mediated by PA
      serving as a putative second messenger. RESULTS: In quiescent fibroblasts,
      exogenous PLD (from Streptomyces chromofuscus) stimulated accumulation of the GTP
      bound form of Ras, activation of mitogen-activated protein (MAP) kinase and DNA
      synthesis, through the pertussis-toxin-sensitive inhibitory G protein Gi.
      Furthermore, PLD mimicked bioactive lysophospholipids (but not PA) in inducing
      Ca2+ mobilization, membrane depolarization and Rho-mediated neurite retraction.
      PLD action was mediated by Iysophosphatidic acid (LPA) derived from
      Iysophosphatidylcholine acting on cognate G-protein-coupled LPA receptor(s).
      There was no evidence for the involvement of PA in mediating the effects of
      exogenous PLD. CONCLUSIONS: Our results provide a molecular explanation for the
      multiple cellular responses to exogenous PLDs. These PLDs generate bioactive LPA
      from pre-existing Iysophosphatidylcholine in the outer membrane leaflet,
      resulting in activation of G-protein-coupled LPA receptors and consequent
      activation of Ras, Rho and Ca2+ signaling pathways. Unscheduled activation of LPA
      receptors may underlie, at least in part, the known pathogenic effects of
      exogenous PLDs.

PMID- 9545199
TI  - Wing development and specification of dorsal cell fates in the absence of
      apterous in Drosophila.
AB  - The development and patterning of the Drosophila wing relies on interactions
      between cell populations that have the anteroposterior (AP) axis and dorsoventral
      (DV) axis of the wing imaginal disc as frames of reference [1-3]. Each of these
      cell populations gives rise to a compartment - a group of cells that have their
      fates restricted by cell lineage - within which cells acquire specific identities
      through the expression of 'selector' genes [1,2,4]. The genes engrailed (en) and
      invected (inv), for example, label cells in the posterior compartment and mediate
      a set of cell interactions that direct the patterning and growth of the wing
      along the AP axis [1,2,4]. A similar situation has been proposed to exist across
      the DV axis, along with apterous (ap) as a dorsal selector gene [5], mediating
      cell interactions by regulating the expression of Serrate (Ser) [6] [7] and
      fringe (fng) [8]. In ap mutants, the wing is lost [5] [9], and here we report
      that this phenotype can be rescued by ectopic expression of either Ser or fng and
      that, surprisingly, the resulting wings have both dorsal and ventral cell fates.

PMID- 9545200
TI  - Direct isolation, phenotyping and cloning of low-frequency antigen-specific
      cytotoxic T lymphocytes from peripheral blood.
AB  - Cytotoxic T lymphocytes (CTLs) play an important role in controlling viral
      infections and certain tumours, but characterising specific CTL responses has
      always been technically limited. Fluorogenic 'tetramers' of major
      histocompatibility complex (MHC) class I complexes have been exploited recently
      to quantify the massive expansion of specific CTLs in human immunodeficiency
      virus (HIV) infection [1]. Here, we use MHC class I complex tetramers to isolate
      low-frequency antigen-specific CTLs directly from human peripheral blood,
      allowing the simultaneous phenotypic and functional characterisation and cloning
      of these CTLs. We synthesised a tetramer that specifically stained human
      leukocyte antigen (HLA)-A2. 1-restricted CTL clones recognising the influenza
      matrix protein peptide 58-66, matrix 58-66 [2]. This tetramer stained between 1
      in 1,500 and 1 in 58,000 peripheral blood mononuclear cells (PBMCs) from HLA
      A2.1+ individuals. The surface phenotype of these cells could be analysed by
      fluorescence-activated cell sorting (FACS), and the cells could be directly
      sorted into enzyme-linked immunospot (ELISpot) plates, where they released
      interferon-gamma (IFN-gamma) within 1 day of antigen exposure. The same
      population was cloned by FACS, and the specificity of several expanded clones was
      confirmed. Cloning was greatly simplified and accelerated compared with standard
      protocols, and was highly efficient. We also used tetramer-based sorting to
      enrich melanoma-specific CTLs derived from a tumour-infiltrated lymph node.
      Direct cloning of specific CTLs from peripheral blood can provide important
      information about immunological memory, CTL responses against tumour antigens and
      CTL proliferation and function, and opens up new possibilities for generating
      CTLs for adoptive immunotherapy.

PMID- 9545201
TI  - Use of a fusion protein between GFP and an actin-binding domain to visualize
      transient filamentous-actin structures.
AB  - Many important processes in eukaryotic cells involve changes in the quantity,
      location and the organization of actin filaments [1] [2] [3]. We have been able
      to visualize these changes in live cells using a fusion protein (GFP-ABD)
      comprising the green fluorescent protein (GFP) of Aequorea victoria and the 25
      kDa highly conserved actin-binding domain (ABD) from the amino terminus of the
      actin cross-linking protein ABP-120 [4]. In live cells of the soil amoeba
      Dictyostelium that were expressing GFP-ABD, the three-dimensional architecture of
      the actin cortex was clearly visualized. The pattern of GFP-ABD fluorescence in
      these cells coincided with that of rhodamine-phalloidin, indicating that GFP-ABD
      specifically binds filamentous (F) actin. On the ventral surface of non-polarized
      vegetative cells, a broad ring of F actin periodically assembled and contracted,
      whereas in polarized cells there were transient punctate F-actin structures;
      cells cycled between the polarized and non-polarized morphologies. During the
      formation of pseudopods, an increase in fluorescence intensity coincided with the
      initial outward deformation of the membrane. This is consistent with the models
      of pseudopod extension that predict an increase in the local density of actin
      filaments. In conclusion, GFP-ABD specifically binds F actin and allows the
      visualization of F-actin dynamics and cellular behavior simultaneously.

PMID- 9545203
TI  - Curiosity and a dash of good luck 

PMID- 9545204
TI  - A lust for science 

PMID- 9545202
TI  - Identification of a common docking topology with substantial variation among
      different TCR-peptide-MHC complexes.
AB  - Whether T-cell receptors (TCRs) recognize antigenic peptides bound to major
      histocompatability complex (MHC) molecules through common or distinct docking
      modes is currently uncertain. We report the crystal structure of a complex
      between the murine N15 TCR [1-4] and its peptide-MHC ligand, an octapeptide
      fragment representing amino acids 52-59 of the vesicular stomatitis virus nuclear
      capsid protein (VSV8) bound to the murine H-2Kb class I MHC molecule. Comparison
      of the structure of the N15 TCR-VSV8-H-2Kb complex with the murine 2C TCR-dEV8-H
      2Kb [5] and the human A6 TCR-Tax-HLA-A2 [6] complexes revealed a common docking
      mode, regardless of TCR specificity or species origin, in which the TCR variable
      Valpha domain overlies the MHC alpha2 helix and the Vbeta domain overlies the MHC
      alpha1 helix. As a consequence, the complementary determining regions CDR1 and
      CDR3 of the TCR Valpha and Vbeta domains make the major contacts with the
      peptide, while the CDR2 loops interact primarily with the MHC. Nonetheless, in
      terms of the details of the relative orientation and disposition of binding,
      there is substantial variation in TCR parameters, which we term twist, tilt and
      shift, and which define the variation of the V module of the TCR relative to the
      MHC antigen-binding groove.

PMID- 9545205
TI  - Negative equity 

PMID- 9545206
TI  - Hidden agenders 

PMID- 9545208
TI  - Cell asymmetry in development.

PMID- 9545210
TI  - Stormy weather in galaxy clusters 
AB  - Recent x-ray, optical, and radio observations coupled with particle and gas
      dynamics numerical simulations reveal an unexpectedly complex environment within
      clusters of galaxies, driven by ongoing accretion of matter from large-scale
      supercluster filaments. Mergers between clusters and continuous infall of dark
      matter and baryons from the cluster periphery produce long-lived "stormy weather"
      within the gaseous cluster atmosphere-shocks, turbulence, and winds of more than
      1000 kilometers per second. This weather may be responsible for shaping a rich
      variety of extended radio sources, which in turn act as "barometers" and
      "anemometers" of cluster weather.

PMID- 9545207
TI  - The NB-ARC domain: a novel signalling motif shared by plant resistance gene
      products and regulators of cell death in animals.

PMID- 9545211
TI  - Protactinium-231 and thorium-230 abundances and high scavenging rates in the
      western arctic ocean 
AB  - The Canadian Basin of the Arctic Ocean, largely ice covered and isolated from
      deep contact with the more dynamic Eurasian Basin by the Lomonosov Ridge, has
      historically been considered an area of low productivity and particle flux and
      sluggish circulation. High-sensitivity mass-spectrometric measurements of the
      naturally occurring radionuclides protactinium-231 and thorium-230 in the deep
      Canada Basin and on the adjacent shelf indicate high particle fluxes and
      scavenging rates in this region. The thorium-232 data suggest that offshore
      advection of particulate material from the shelves contributes to scavenging of
      reactive materials in areas of permanent ice cover.

PMID- 9545212
TI  - Is GRO J1744-28 a strange star? 
AB  - The unusual hard x-ray burster GRO J1744-28 recently discovered by the Compton
      Gamma-Ray Observatory can be modeled as a strange star with a dipolar magnetic
      field of </=10(11) gauss. According to this model, when the accreted mass of the
      star exceeds some critical mass, its crust breaks, resulting in the conversion of
      the accreted matter into strange matter and a release of energy. Subsequently, a
      fireball forms and expands relativistically outward. The expanding fireball
      interacts with the surrounding interstellar medium, causing its kinetic energy to
      be radiated in shock waves and producing a burst of x-ray radiation. The burst
      energy, duration, interval, and spectrum derived from such a model are consistent
      with the observations of GRO J1744-28.

PMID- 9545213
TI  - Two-fraction model of initial sediment motion in gravel-Bed rivers 
AB  - The prediction of sediment transport in gravel-bed rivers is essential to the
      management of land, water, and ecological resources in mountain regions. Dividing
      the bed sediment into two populations-sand and gravel-permits realistic and
      useful predictions of the onset of sediment transport. The critical flow
      initiating grain motion decreases rapidly with sand content over the transition
      from a gravel-framework bed to a sand-matrix bed. The two-fraction model provides
      a simple means of forecasting the movement of excess fine sediment supply. The
      model also helps to explain the development of the abrupt gravel-sand transition
      commonly observed in natural rivers.

PMID- 9545214
TI  - Formation of carbonates in the Tatahouine meteorite.
AB  - The Tatahouine meteorite, in southern Tunisia, shows terrestrial contamination
      that developed during 63 years of exposure on Earth's surface. Samples collected
      on the day of the fall in 1931 contained fractures, with no secondary minerals,
      whereas samples collected in 1994 contain calcite aggregates (70 to 150
      micrometers) and rod-shaped forms (100 to 600 nanometers in length and 70 to 80
      nanometers in diameter) on the fractures. Carbon isotope analysis of the
      carbonates within the Tatahouine meteorite [delta13C = -2.0 per mil Pee Dee
      belemnite standard (PDB)] and the underlying ground (delta13C = -3.2 per mil PDB)
      confirm their terrestrial origin.

PMID- 9545216
TI  - Osmium isotopic evidence for ancient subcontinental lithospheric mantle beneath
      the kerguelen islands, southern indian ocean 
AB  - Upper mantle xenoliths found in ocean island basalts are an important window
      through which the oceanic mantle lithosphere may be viewed directly. Osmium
      isotopic data on peridotite xenoliths from the Kerguelen Islands, an archipelago
      that is located on the northern Kerguelen Plateau in the southern Indian Ocean,
      demonstrate that pieces of mantle of diverse provenance are present beneath the
      Islands. In particular, peridotites with unradiogenic osmium and ancient rhenium
      depletion ages (to 1.36 x 10(9) years old) may be pieces of the Gondwanaland
      subcontinental lithosphere that were incorporated into the Indian Ocean
      lithosphere as a result of the rifting process.

PMID- 9545215
TI  - Oxygen isotopic abundances in calcium- aluminum-rich inclusions from ordinary
      chondrites: implications for nebular heterogeneity.
AB  - The oxygen isotopic compositions of two calcium-aluminum-rich inclusions (CAIs)
      from the unequilibrated ordinary chondrite meteorites Quinyambie and Semarkona
      are enriched in 16O by an amount similar to that in CAIs from carbonaceous
      chondrites. This may indicate that most CAIs formed in a restricted region of the
      solar nebula and were then unevenly distributed throughout the various chondrite
      accretion regions. The Semarkona CAI is isotopically homogeneous and contains
      highly 16O-enriched melilite, supporting the hypothesis that all CAI minerals
      were originally 16O-rich, but that in most carbonaceous chondrite inclusions some
      minerals exchanged oxygen isotopes with an external reservoir following
      crystallization.

PMID- 9545218
TI  - A monolithic photovoltaic-photoelectrochemical device for hydrogen production via
      water splitting 
AB  - Direct water electrolysis was achieved with a novel, integrated, monolithic
      photoelectrochemical-photovoltaic design. This photoelectrochemical cell, which
      is voltage biased with an integrated photovoltaic device, splits water directly
      upon illumination; light is the only energy input. The hydrogen production
      efficiency of this system, based on the short-circuit current and the lower
      heating value of hydrogen, is 12.4 percent.

PMID- 9545217
TI  - Unitary control in quantum ensembles: maximizing signal intensity in coherent
      spectroscopy 
AB  - Experiments in coherent magnetic resonance, microwave, and optical spectroscopy
      control quantum-mechanical ensembles by guiding them from initial states toward
      target states by unitary transformation. Often, the coherences detected as
      signals are represented by a non-Hermitian operator. Hence, spectroscopic
      experiments, such as those used in nuclear magnetic resonance, correspond to
      unitary transformations between operators that in general are not Hermitian. A
      gradient-based systematic procedure for optimizing these transformations is
      described that finds the largest projection of a transformed initial operator
      onto the target operator and, thus, the maximum spectroscopic signal. This method
      can also be used in applied mathematics and control theory.

PMID- 9545220
TI  - Association of the AP-3 adaptor complex with clathrin.
AB  - A heterotetrameric complex termed AP-3 is involved in signal-mediated protein
      sorting to endosomal-lysosomal organelles. AP-3 has been proposed to be a
      component of a nonclathrin coat. In vitro binding assays showed that mammalian AP
      3 did associate with clathrin by interaction of the appendage domain of its beta3
      subunit with the amino-terminal domain of the clathrin heavy chain. The beta3
      appendage domain contained a conserved consensus motif for clathrin binding. AP-3
      colocalized with clathrin in cells as observed by immunofluorescence and
      immunoelectron microscopy. Thus, AP-3 function in protein sorting may depend on
      clathrin.

PMID- 9545219
TI  - Gastrointestinal tract as a major site of CD4+ T cell depletion and viral
      replication in SIV infection.
AB  - Human and simian immunodeficiency virus (HIV and SIV) replicate optimally in
      activated memory CD4(+) T cells, a cell type that is abundant in the intestine.
      SIV infection of rhesus monkeys resulted in profound and selective depletion of
      CD4+ T cells in the intestine within days of infection, before any such changes
      in peripheral lymphoid tissues. The loss of CD4+ T cells in the intestine
      occurred coincident with productive infection of large numbers of mononuclear
      cells at this site. The intestine appears to be a major target for SIV
      replication and the major site of CD4+ T cell loss in early SIV infection.

PMID- 9545221
TI  - NMR structure of a classical pseudoknot: interplay of single- and double-stranded
      RNA.
AB  - Pseudoknot formation folds the 3' ends of many plant viral genomic RNAs into
      structures that resemble transfer RNA in global folding and in their reactivity
      to transfer RNA-specific proteins. The solution structure of the pseudoknotted T
      arm and acceptor arm of the transfer RNA-like structure of turnip yellow mosaic
      virus (TYMV) was determined by nuclear magnetic resonance (NMR) spectroscopy. The
      molecule is stabilized by the hairpin formed by the 5' end of the RNA, and by the
      intricate interactions related to the loops of the pseudoknot. Loop 1 spans the
      major groove of the helix with only two of its four nucleotides. Loop 2, which
      crosses the minor groove, interacts closely with its opposing helix, in
      particular through hydrogen bonds with a highly conserved adenine. The structure
      resulting from this interaction between the minor groove and single-stranded RNA
      at helical junctions displays internal mobility, which may be a general feature
      of RNA pseudoknots that regulates their interaction with proteins or other RNA
      molecules.

PMID- 9545222
TI  - Autoinducer of virulence as a target for vaccine and therapy against
      Staphylococcus aureus.
AB  - Staphylococcus aureus causes pathologies ranging from minor skin infections to
      life-threatening diseases. Pathogenic effects are largely due to production of
      bacterial toxin, which is regulated by an RNA molecule, RNAIII. The S. aureus
      protein called RAP (RNAIII activating protein) activates RNAIII, and a peptide
      called RIP (RNAIII inhibiting peptide), produced by a nonpathogenic bacteria,
      inhibits RNAIII. Mice vaccinated with RAP or treated with purified or synthetic
      RIP were protected from S. aureus pathology. Thus, these two molecules may
      provide useful approaches for the prevention and treatment of diseases caused by
      S. aureus.

PMID- 9545223
TI  - Impacts of rising atmospheric carbon dioxide on model terrestrial ecosystems 
AB  - In model terrestrial ecosystems maintained for three plant generations at
      elevated concentrations of atmospheric carbon dioxide, increases in
      photosynthetically fixed carbon were allocated below ground, raising
      concentrations of dissolved organic carbon in soil. These effects were then
      transmitted up the decomposer food chain. Soil microbial biomass was unaffected,
      but the composition of soil fungal species changed, with increases in rates of
      cellulose decomposition. There were also changes in the abundance and species
      composition of Collembola, fungal-feeding arthropods. These results have
      implications for long-term feedback processes in soil ecosystems that are subject
      to rising global atmospheric carbon dioxide concentrations.

PMID- 9545224
TI  - Control of alternative splicing of potassium channels by stress hormones.
AB  - Many molecular mechanisms for neural adaptation to stress remain unknown.
      Expression of alternative splice variants of Slo, a gene encoding calcium- and
      voltage-activated potassium channels, was measured in rat adrenal chromaffin
      tissue from normal and hypophysectomized animals. Hypophysectomy triggered an
      abrupt decrease in the proportion of Slo transcripts containing a "STREX" exon.
      The decrease was prevented by adrenocorticotropic hormone injections. In Xenopus
      oocytes, STREX variants produced channels with functional properties associated
      with enhanced repetitive firing. Thus, the hormonal stress axis is likely to
      control the excitable properties of epinephrine-secreting cells by regulating
      alternative splicing of Slo messenger RNA.

PMID- 9545225
TI  - Maternal control of embryogenesis by MEDEA, a polycomb group gene in Arabidopsis.
AB  - The gametophytic maternal effect mutant medea (mea) shows aberrant growth
      regulation during embryogenesis in Arabidopsis thaliana. Embryos derived from mea
      eggs grow excessively and die during seed desiccation. Embryo lethality is
      independent of the paternal contribution and gene dosage. The mea phenotype is
      consistent with the parental conflict theory for the evolution of parent-of
      origin-specific effects. MEA encodes a SET domain protein similar to Enhancer of
      zeste, a member of the Polycomb group. In animals, Polycomb group proteins ensure
      the stable inheritance of expression patterns through cell division and regulate
      the control of cell proliferation.

PMID- 9545226
TI  - Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the
      thymus.
AB  - Degradation of invariant chain (Ii) is a critical step in major
      histocompatibility complex class II-restricted antigen presentation. Cathepsin L
      was found to be necessary for Ii degradation in cortical thymic epithelial cells
      (cTECs), but not in bone marrow (BM)-derived antigen-presenting cells (APCs).
      Consequently, positive selection of CD4+ T cells was reduced. Because different
      cysteine proteinases are responsible for specific Ii degradation steps in cTECs
      and BM-derived APCs, the proteolytic environment in cells mediating positive and
      negative selection may be distinct. The identification of a protease involved in
      class II presentation in a tissue-specific manner suggests a potential means of
      manipulating CD4+ T cell responsiveness in vivo.

PMID- 9545227
TI  - Perturbation of beta1-integrin function alters the development of murine mammary
      gland.
AB  - The expression of a transgene coding for a chimeric molecule, containing the
      cytoplasmic and transmembrane domains of the beta1-integrin chain and the
      extracellular domain of the T-cell differentiation antigen CD4, was targeted to
      the mouse mammary gland by the mouse mammary tumor virus (MMTV) promoter. The
      chimera does not interact with the extracellular ligands; however, its expression
      in cultured cells was shown to interfere with focal adhesion kinase (FAK)
      phosphorylation following ligation of endogenous beta1-integrin. Therefore,
      expression of the transgenic protein on the cell surface should uncouple adhesion
      from intracellular events associated with the beta1-cytoplasmic domain and thus
      perturb beta1-integrin functions. Although most of the transgenic females were
      able to lactate, their mammary glands had a phenotype clearly distinct from that
      of wild-type mice. At mid-pregnancy and the beginning of lactation, transgenic
      glands were underdeveloped and the epithelial cell proliferation rates were
      decreased, while the apoptosis levels were higher than in wild-type glands. In
      lactation, the amounts of the whey acidic protein (WAP) and beta-casein gene
      transcripts were diminished, and the basement membrane component, laminin and the
      beta4-integrin chain accumulated at the lateral surface of luminal epithelial
      cells, revealing defects in polarization. Our observations prove that in vivo,
      beta1-integrins are involved in control of proliferation, apoptosis,
      differentiation and maintenance of baso-apical polarity of mammary epithelial
      cells, and therefore are essential for normal mammary gland development and
      function.

PMID- 9545228
TI  - Dileucine-based sorting signals bind to the beta chain of AP-1 at a site distinct
      and regulated differently from the tyrosine-based motif-binding site.
AB  - In previous work, we showed that peptides from endocytosed proteins containing
      the tyrosine YXXphi sorting motif are recognized by the mu 2 subunit of AP-2, the
      plasma membrane clathrin adaptor protein complex. This interaction is activated
      by phosphoinositide lipids that are phosphorylated at the D-3 position of the
      inositol ring, and is also enhanced by the formation of clathrin-AP-2 coats.
      Here, we describe the detection of a specific interaction between peptides
      containing a second sorting motif, the dileucine motif, and AP-1, the clathrin
      adaptor complex responsible for sorting proteins at the trans-Golgi network
      (TGN). Surprisingly, the site of dileucine binding is the beta1 subunit, not mu
      1. A YXXphi-containing peptide from a protein trafficked within the TGN does bind
      to mu 1, however. Phosphatidylinositol 3,4-diphosphate and 3,4, 5-triphosphate
      did not activate the interaction between dileucine-containing peptides and AP-1
      but instead inhibited it, and clathrin-AP-1 coat formation did not alter the
      interaction. Thus, there are at least two physically separate binding sites for
      sorting signals on APs, which are also regulated independently.

PMID- 9545229
TI  - Initial docking of ER-derived vesicles requires Uso1p and Ypt1p but is
      independent of SNARE proteins.
AB  - ER-to-Golgi transport in yeast may be reproduced in vitro with washed membranes,
      purified proteins (COPII, Uso1p and LMA1) and energy. COPII coated vesicles that
      have budded from the ER are freely diffusible but then dock to Golgi membranes
      upon the addition of Uso1p. LMA1 and Sec18p are required for vesicle fusion after
      Uso1p function. Here, we report that the docking reaction is sensitive to excess
      levels of Sec19p (GDI), a treatment that removes the GTPase, Ypt1p. Once docked,
      however, vesicle fusion is no longer sensitive to GDI. In vitro binding
      experiments demonstrate that the amount of Uso1p associated with membranes is
      reduced when incubated with GDI and correlates with the level of membrane-bound
      Ypt1p, suggesting that this GTPase regulates Uso1p binding to membranes. To
      determine the influence of SNARE proteins on the vesicle docking step,
      thermosensitive mutations in Sed5p, Bet1p, Bos1p and Sly1p that prevent ER-to
      Golgi transport in vitro at restrictive temperatures were employed. These
      mutations do not interfere with Uso1p-mediated docking, but block membrane
      fusion. We propose that an initial vesicle docking event of ER-derived vesicles,
      termed tethering, depends on Uso1p and Ypt1p but is independent of SNARE
      proteins.

PMID- 9545230
TI  - A novel EspA-associated surface organelle of enteropathogenic Escherichia coli
      involved in protein translocation into epithelial cells.
AB  - Enteropathogenic Escherichia coli (EPEC), like many bacterial pathogens, employ a
      type III secretion system to deliver effector proteins across the bacterial cell.
      In EPEC, four proteins are known to be exported by a type III secretion
      system_EspA, EspB and EspD required for subversion of host cell signal
      transduction pathways and a translocated intimin receptor (Tir) protein (formerly
      Hp90) which is tyrosine-phosphorylated following transfer to the host cell to
      become a receptor for intimin-mediated intimate attachment and 'attaching and
      effacing' (A/E) lesion formation. The structural basis for protein translocation
      has yet to be fully elucidated for any type III secretion system. Here, we
      describe a novel EspA-containing filamentous organelle that is present on the
      bacterial surface during the early stage of A/E lesion formation, forms a
      physical bridge between the bacterium and the infected eukaryotic cell surface
      and is required for the translocation of EspB into infected epithelial cells.

PMID- 9545231
TI  - Ramifications of kinetic partitioning on usher-mediated pilus biogenesis.
AB  - The biogenesis of diverse adhesive structures in a variety of Gram-negative
      bacterial species is dependent on the chaperone/usher pathway. Very little is
      known about how the usher protein translocates protein subunits across the outer
      membrane or how assembly of these adhesive structures occurs. We have discovered
      several mechanisms by which the usher protein acts to regulate the ordered
      assembly of type 1 pili, specifically through critical interactions of the
      chaperone-adhesin complex with the usher. A study of association and dissociation
      events of chaperone-subunit complexes with the usher in real time using surface
      plasmon resonance revealed that the chaperone-adhesin complex has the tightest
      and fastest association with the usher. This suggests that kinetic partitioning
      of chaperone-adhesin complexes to the usher is a defining factor in tip
      localization of the adhesin in the pilus. Furthermore, we identified and purified
      a chaperone-adhesin-usher assembly intermediate that was formed in vivo. Trypsin
      digestion assays showed that the usher in this complex was in an altered
      conformation, which was maintained during pilus assembly. The data support a
      model in which binding of the chaperone-adhesin complex to the usher stabilizes
      the usher in an assembly-competent conformation and allows initiation of pilus
      assembly.

PMID- 9545232
TI  - ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class
      I assembly.
AB  - The assembly of newly synthesized MHC class I molecules within the endoplasmic
      reticulum and their association with the transporter associated with antigen
      processing (TAP) is a process involving the chaperones calnexin and calreticulin.
      Using peptide mapping by matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry to identify a new component, we now introduce a third molecular
      chaperone, the thiol-dependent reductase ER-60 (ERp57/GRP58/ERp61/HIP-70/Q2),
      into this process. ER-60 is found in MHC class I heavy chain complexes with
      calnexin that are generated early during the MHC class I assembly pathway. The
      thiol reductase activity of ER-60 raises the possibility that ER-60 is involved
      in the disulfide bond formation within heavy chains. In addition, ER-60 is part
      of the late assembly complexes consisting of MHC class I, tapasin, TAP,
      calreticulin and calnexin. In a beta2-microglobulin (beta2m)-negative mouse cell
      line, S3, ER-60-calnexin-heavy chain complexes are shown to bind to TAP,
      suggesting that beta2m is not required for the association of MHC class I heavy
      chains with TAP.

PMID- 9545234
TI  - A novel protein modification pathway related to the ubiquitin system.
AB  - Ubiquitin conjugation is known to target protein substrates primarily to
      degradation by the proteasome or via the endocytic route. Here we describe a
      novel protein modification pathway in yeast which mediates the conjugation of
      RUB1, a ubiquitin-like protein displaying 53% amino acid identity to ubiquitin.
      We show that RUB1 conjugation requires at least three proteins in vivo. ULA1 and
      UBA3 are related to the N- and C-terminal domains of the E1 ubiquitin-activating
      enzyme, respectively, and together fulfil E1-like functions for RUB1 activation.
      RUB1 conjugation also requires UBC12, a protein related to E2 ubiquitin
      conjugating enzymes, which functions analogously to E2 enzymes in RUB1-protein
      conjugate formation. Conjugation of RUB1 is not essential for normal cell growth
      and appears to be selective for a small set of substrates. Remarkably,
      CDC53/cullin, a common subunit of the multifunctional SCF ubiquitin ligase, was
      found to be a major substrate for RUB1 conjugation. This suggests that the RUB1
      conjugation pathway is functionally affiliated to the ubiquitin-proteasome system
      and may play a regulatory role.

PMID- 9545233
TI  - Mtr10p functions as a nuclear import receptor for the mRNA-binding protein Npl3p.
AB  - MTR10, previously shown to be involved in mRNA export, was found in a synthetic
      lethal relationship with nucleoporin NUP85. Green fluorescent protein (GFP)
      tagged Mtr10p localizes preferentially inside the nucleus, but a nuclear pore and
      cytoplasmic distribution is also evident. Purified Mtr10p forms a complex with
      Npl3p, an RNA-binding protein that shuttles in and out of the nucleus. In mtr10
      mutants, nuclear uptake of Npl3p is strongly impaired at the restrictive
      temperature, while import of a classic nuclear localization signal (NLS)
      containing protein is not. Accordingly, the NLS within Npl3p is extended and
      consists of the RGG box plus a short and non-repetitive C-terminal tail. Mtr10p
      interacts in vitro with Gsp1p-GTP, but with low affinity. Interestingly, Npl3p
      dissociates from Mtr10p only by incubation with Ran-GTP plus RNA. This suggests
      that Npl3p follows a distinct nuclear import pathway and that intranuclear
      release from its specific import receptor Mtr10p requires the cooperative action
      of both Ran-GTP and newly synthesized mRNA.

PMID- 9545235
TI  - IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct
      inhibition of distinct caspases.
AB  - Inhibitor of apoptosis (IAP) gene products play an evolutionarily conserved role
      in regulating programmed cell death in diverse species ranging from insects to
      humans. Human XIAP, cIAP1 and cIAP2 are direct inhibitors of at least two members
      of the caspase family of cell death proteases: caspase-3 and caspase-7. Here we
      compared the mechanism by which IAPs interfere with activation of caspase-3 and
      other effector caspases in cytosolic extracts where caspase activation was
      initiated by caspase-8, a proximal protease activated by ligation of TNF-family
      receptors, or by cytochrome c, which is released from mitochondria into the
      cytosol during apoptosis. These studies demonstrate that XIAP, cIAP1 and cIAP2
      can prevent the proteolytic processing of pro-caspases -3, -6 and -7 by blocking
      the cytochrome c-induced activation of pro-caspase-9. In contrast, these IAP
      family proteins did not prevent caspase-8-induced proteolytic activation of pro
      caspase-3; however, they subsequently inhibited active caspase-3 directly, thus
      blocking downstream apoptotic events such as further activation of caspases.
      These findings demonstrate that IAPs can suppress different apoptotic pathways by
      inhibiting distinct caspases and identify pro-caspase-9 as a new target for IAP
      mediated inhibition of apoptosis.

PMID- 9545236
TI  - Caspase-mediated activation and induction of apoptosis by the mammalian Ste20
      like kinase Mst1.
AB  - Mst1 is a ubiquitously expressed serine-threonine kinase, homologous to the
      budding yeast Ste20, whose physiological regulation and cellular function are
      unknown. In this paper we show that Mst1 is specifically cleaved by a caspase 3
      like activity during apoptosis induced by either cross-linking CD95/Fas or by
      staurosporine treatment. CD95/Fas-induced cleavage of Mst1 was blocked by the
      cysteine protease inhibitor ZVAD-fmk, the more selective caspase inhibitor DEVD
      CHO and by the viral serpin CrmA. Caspase-mediated cleavage of Mst1 removes the C
      terminal regulatory domain and correlates with an increase in Mst1 activity in
      vivo, consistent with caspase-mediated cleavage activating Mst1. Overexpression
      of either wild-type Mst1 or a truncated mutant induces morphological changes
      characteristic of apoptosis. Furthermore, exogenously expressed Mst1 is cleaved,
      indicating that Mst1 can activate caspases that result in its cleavage. Kinase
      dead Mst1 did not induce morphological alterations and was not cleaved upon
      overexpression, indicating that Mst1 must be catalytically active in order to
      mediate these effects. Mst1 activates MKK6, p38 MAPK, MKK7 and SAPK in co
      transfection assays, suggesting that Mst1 may activate these pathways. Our
      findings suggest the existence of a positive feedback loop involving Mst1, and
      possibly the SAPK and p38 MAPK pathways, which serves to amplify the apoptotic
      response.

PMID- 9545237
TI  - Cell wall integrity modulates RHO1 activity via the exchange factor ROM2.
AB  - The essential phosphatidylinositol kinase homologue TOR2 of Saccharomyces
      cerevisiae controls the actin cytoskeleton by activating a GTPase switch
      consisting of RHO1 (GTPase), ROM2 (GEF) and SAC7 (GAP). We have identified two
      mutations, rot1-1 and rot2-1, that suppress the loss of TOR2 and are synthetic
      lethal. The wild-type ROT1 and ROT2 genes and a multicopy suppressor, BIG1, were
      isolated by their ability to rescue the rot1-1 rot2-1 double mutant. ROT2 encodes
      glucosidase II, and ROT1 and BIG1 encode novel proteins. We present evidence that
      cell wall defects activate RHO1. First, rot1, rot2, big1, cwh41, gas1 and fks1
      mutations all confer cell wall defects and suppress tor2(ts). Second,
      destabilizing the cell wall by supplementing the growth medium with 0.005% SDS
      also suppresses a tor2(ts) mutation. Third, disturbing the cell wall with SDS or
      a rot1, rot2, big1, cwh41, gas1 or fks1 mutation increases GDP/GTP exchange
      activity toward RHO1. These results suggest that cell wall defects suppress a
      tor2 mutation by activating RHO1 independently of TOR2, thereby inducing TOR2
      independent polarization of the actin cytoskeleton and cell wall synthesis.
      Activation of RHO1, a subunit of the cell wall synthesis enzyme glucan synthase,
      by a cell wall alteration would ensure that cell wall synthesis occurs only when
      and where needed. The mechanism of RHO1 activation by a cell wall alteration is
      via the exchange factor ROM2 and could be analogous to signalling by integrin
      receptors in mammalian cells.

PMID- 9545238
TI  - Membrane-targeting sequences on AKAP79 bind phosphatidylinositol-4, 5
      bisphosphate.
AB  - Protein kinases and phosphatases are targeted through association with anchoring
      proteins that tether the enzymes to subcellular structures and organelles.
      Through in situ fluorescent techniques using a Green Fluorescent Protein tag, we
      have mapped membrane-targeting domains on AKAP79, a multivalent anchoring protein
      that binds the cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and
      protein phosphatase 2B, calcineurin (CaN). Three linear sequences termed region A
      (residues 31-52), region B (residues 76-101) and region C (residues 116-145)
      mediate targeting of AKAP79 in HEK-293 cells and cortical neurons. Analysis of
      these targeting sequences suggests that they contain putative phosphorylation
      sites for PKA and PKC and are rich in basic and hydrophobic amino acids similar
      to a class of membrane-targeting domains which bind acidic phospholipids and
      calmodulin. Accordingly, the AKAP79 basic regions mediate binding to membrane
      vesicles containing acidic phospholipids including phosphatidylinositol-4, 5
      bisphosphate [PtdIns(4,5)P2] and this binding is regulated by phosphorylation and
      calcium-calmodulin. Finally, AKAP79 was shown to be phosphorylated in HEK-293
      cells following stimulation of PKA and PKC, and activation of PKC or calmodulin
      was shown to release AKAP79 from membrane particulate fractions. These findings
      suggest that AKAP79 might function in cells not only as an anchoring protein but
      also as a substrate and effector for the anchored kinases and phosphatases.

PMID- 9545240
TI  - Calmodulin controls the rod photoreceptor CNG channel through an unconventional
      binding site in the N-terminus of the beta-subunit.
AB  - Calmodulin (CaM) controls the activity of the rod cGMP-gated ion channel by
      decreasing the apparent cGMP affinity. We have examined the mechanism of this
      modulation using electrophysiological and biochemical techniques. Heteromeric
      channels, consisting of alpha- and beta-subunits, display a high CaM sensitivity
      (EC50 </=5 nM) similar to the native channel. Using surface plasmon resonance
      spectroscopy, we identified two unconventional CaM-binding sites (CaM1 and CaM2),
      one in each of the N- and the C-terminal regions of the beta-subunit. Ca2+ co
      operatively stimulates binding of CaM to these sites exactly within the range of
      [Ca2+] occurring during a light response. Deletion of the N-terminal CaM1 site
      results in channels that are no longer CaM-sensitive, whereas deletion of CaM2
      has only minor effects. We discuss different models to explain the high-affinity
      binding of CaM.

PMID- 9545239
TI  - A novel lipid-anchored A-kinase Anchoring Protein facilitates cAMP-responsive
      membrane events.
AB  - Compartmentalization of protein kinases with substrates is a mechanism that may
      promote specificity of intracellular phosphorylation events. We have cloned a low
      molecular weight A-kinase Anchoring Protein, called AKAP18, which targets the
      cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits
      functional coupling to the L-type calcium channel. Membrane anchoring is mediated
      by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5
      which are lipid-modified through myristoylation and dual palmitoylation,
      respectively. Transient transfection of AKAP18 into HEK-293 cells expressing the
      cardiac L-type Ca2+ channel promoted a 34 9% increase in cAMP-responsive Ca2+
      currents. In contrast, a targeting-deficient mutant of AKAP18 had no effect on
      Ca2+ currents in response to the application of a cAMP analog. Further studies
      demonstrate that AKAP18 facilitates GLP-1-mediated insulin secretion in a
      pancreatic beta cell line (RINm5F), suggesting that membrane anchoring of the
      kinase participates in physiologically relevant cAMP-responsive events that may
      involve ion channel activation.

PMID- 9545241
TI  - Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C
      interactions essential for G protein-coupled signaling.
AB  - Drosophila INAD, which contains five tandem protein interaction PDZ domains,
      plays an important role in the G protein-coupled visual signal transduction.
      Mutations in InaD alleles display mislocalization of signaling molecules of
      phototransduction which include the essential effector, phospholipase C-beta (PLC
      beta), which is also known as NORPA. The molecular and biochemical details of
      this functional link are unknown. We report that INAD directly binds to NORPA via
      two terminally positioned PDZ1 and PDZ5 domains. PDZ1 binds to the C-terminus of
      NORPA, while PDZ5 binds to an internal region overlapping with the G box-homology
      region (a putative G protein-interacting site). The NORPA proteins lacking
      binding sites, which display normal basal PLC activity, can no longer associate
      with INAD in vivo. These truncations cause significant reduction of NORPA protein
      expression in rhabdomeres and severe defects in phototransduction. Thus, the two
      terminal PDZ domains of INAD, through intermolecular and/or intramolecular
      interactions, are brought into proximity in vivo. Such domain organization allows
      for the multivalent INAD-NORPA interactions which are essential for G protein
      coupled phototransduction.

PMID- 9545242
TI  - Xvent-1 mediates BMP-4-induced suppression of the dorsal-lip-specific early
      response gene XFD-1' in Xenopus embryos.
AB  - Ectopic expression of the ventralizing morphogen BMP-4 (bone morphogenetic
      protein-4) in the dorsal lip (Spemann organizer) of Xenopus embryos blocks
      transcription of dorsal-lip-specific early response genes. We investigated the
      molecular mechanism underlying the BMP-4-induced inhibition of the fork head gene
      XFD-1'. The promoter of this gene contains a BMP-triggered inhibitory element
      (BIE) which prevents activation of this gene at the ventral/vegetal side of the
      embryo in vivo. In the present study, we show that BMP-4-induced inhibition is
      not direct but indirect, and is mediated by Xvent homeobox proteins. Micro
      injections of Xvent-1 RNA and XFD-1' promoter deletion mutants demonstrate that
      Xvent-1 mimics the effect of BMP-4 signalling not only by suppression of the XFD
      1' gene, but also by utilizing the BIE. Suppression could be reverted using a
      dominant-negative Xvent-1 mutant. The repressor domain was localized to the N
      terminal region of the protein. Gel-shift and footprint analyses prove that Xvent
      1 binds to the BIE. Moreover, PCR-based target-site selection for the Xvent-1
      homeodomain confirms distinct motifs within the BIE as preferential binding
      sites. Thus, biological and molecular data suggest that Xvent-1 acts as direct
      repressor for XFD-1' transcription and mediates BMP-4-induced inhibition.

PMID- 9545243
TI  - A phosphorylation site in the ftz homeodomain is required for activity.
AB  - The Drosophila homeodomain-containing protein Fushi tarazu (Ftz) is expressed
      sequentially in the embryo, first in alternate segments, then in specific
      neuroblasts and neurons in the central nervous system, and finally in parts of
      the gut. During these different developmental stages, the protein is heavily
      phosphorylated on different subsets of Ser and Thr residues. This stage-specific
      phosphorylation suggests possible roles for signal transduction pathways in
      directing tissue-specific Ftz activities. Here we show that one of the Ftz
      phosphorylation sites, T263 in the N-terminus of the Ftz homeodomain, is
      phosphorylated in vitro by Drosophila embryo extracts and protein kinase A. In
      the embryo, mutagenesis of this site to the non-phosphorylatable residue Ala
      resulted in loss of ftz-dependent segments. Conversely, substitution of T263 with
      Asp, which is also non-phosphorylatable, but which successfully mimics
      phosphorylated residues in a number of proteins, rescued the mutant phenotype.
      This suggests that T263 is in the phosphorylated state when functioning normally
      in vivo. We also demonstrate that the T263 substitutions of Ala and Asp do not
      affect Ftz DNA-binding activity in vitro, nor do they affect stability or
      transcriptional activity in transfected S2 cells. This suggests that T263
      phosphorylation is most likely required for a homeodomain-mediated interaction
      with an embryonically expressed protein.

PMID- 9545245
TI  - Erythroid Kruppel-like factor (EKLF) is active in primitive and definitive
      erythroid cells and is required for the function of 5'HS3 of the beta-globin
      locus control region.
AB  - Disruption of the gene for transcription factor EKLF (erythroid Kruppel-like
      factor) results in fatal anaemia caused by severely reduced expression of the
      adult beta-globin gene, while other erythroid-specific genes, including the
      embryonic epsilon- and fetal gamma-globin genes, are expressed normally. Thus,
      EKLF is thought to be a stage-specific factor acting through the CACC box in the
      beta-gene promoter, even though it is already present in embryonic red cells.
      Here, we show that a beta-globin gene linked directly to the locus control region
      (LCR) is expressed at embryonic stages, and that this is only modestly reduced in
      EKLF-/- embryos. Thus, embryonic beta-globin expression is not intrinsically
      dependent on EKLF. To investigate whether EKLF functions in the locus control
      region, we analysed the expression of LCR-driven lacZ reporters. This shows that
      EKLF is not required for reporter activation by the complete LCR. However,
      embryonic expression of reporters driven by 5'HS3 of the LCR requires EKLF. This
      suggests that EKLF interacts directly with the CACC motifs in 5'HS3 and
      demonstrates that EKLF is also a transcriptional activator in embryonic
      erythropoiesis. Finally, we show that overexpression of EKLF results in an
      earlier switch from gamma- to beta-globin expression. Adult mice with the EKLF
      transgene have reduced platelet counts, suggesting that EKLF levels affect the
      balance between the megakaryocytic and erythroid lineages. Interestingly, the
      EKLF transgene rescues the lethal phenotype of EKLF null mice, setting the stage
      for future studies aimed at the analysis of the EKLF protein and its role in beta
      globin gene activation.

PMID- 9545244
TI  - Identification of BSAP (Pax-5) target genes in early B-cell development by loss-
      and gain-of-function experiments.
AB  - The Pax-5 gene codes for the transcription factor BSAP which is essential for the
      progression of adult B lymphopoiesis beyond an early progenitor (pre-BI) cell
      stage. Although several genes have been proposed to be regulated by BSAP, CD19 is
      to date the only target gene which has been genetically confirmed to depend on
      this transcription factor for its expression. We have now taken advantage of
      cultured pre-BI cells of wild-type and Pax-5 mutant bone marrow to screen a large
      panel of B lymphoid genes for additional BSAP target genes. Four differentially
      expressed genes were shown to be under the direct control of BSAP, as their
      expression was rapidly regulated in Pax-5-deficient pre-BI cells by a hormone
      inducible BSAP-estrogen receptor fusion protein. The genes coding for the B-cell
      receptor component Ig-alpha (mb-1) and the transcription factors N-myc and LEF-1
      are positively regulated by BSAP, while the gene coding for the cell surface
      protein PD-1 is efficiently repressed. Distinct regulatory mechanisms of BSAP
      were revealed by reconstituting Pax-5-deficient pre-BI cells with full-length
      BSAP or a truncated form containing only the paired domain. IL-7 signalling was
      able to efficiently induce the N-myc gene only in the presence of full-length
      BSAP, while complete restoration of CD19 synthesis was critically dependent on
      the BSAP protein concentration. In contrast, the expression of the mb-1 and LEF-1
      genes was already reconstituted by the paired domain polypeptide lacking any
      transactivation function, suggesting that the DNA-binding domain of BSAP is
      sufficient to recruit other transcription factors to the regulatory regions of
      these two genes. In conclusion, these loss- and gain-of-function experiments
      demonstrate that BSAP regulates four newly identified target genes as a
      transcriptional activator, repressor or docking protein depending on the specific
      regulatory sequence context.

PMID- 9545246
TI  - Rb binds c-Jun and activates transcription.
AB  - The retinoblastoma protein (Rb) acts as a critical cell-cycle regulator and loss
      of Rb function is associated with a variety of human cancer types. Here we report
      that Rb binds to members of the AP-1 family of transcription factors, including c
      Jun, and stimulates c-Jun transcriptional activity from an AP-1 consensus
      sequence. The interaction involves the leucine zipper region of c-Jun and the B
      pocket of Rb as well as a C-terminal domain. We also present evidence that the
      complexes are found in terminally differentiating keratinocytes and cells
      entering the G1 phase of the cell cycle after release from serum starvation. The
      human papillomavirus type 16 E7 protein, which binds to both c-Jun and Rb,
      inhibits the ability of Rb to activate c-Jun. The results provide evidence of a
      role for Rb as a transcriptional activator in early G1 and as a potential
      modulator of c-Jun expression during keratinocyte differentiation.

PMID- 9545247
TI  - Structure of wild-type yeast RNA polymerase II and location of Rpb4 and Rpb7.
AB  - The three-dimensional structure of wild-type yeast RNA polymerase II has been
      determined at a nominal resolution of 24 A. A difference map between this
      structure and that of the polymerase lacking subunits Rpb4 and Rpb7 showed these
      two subunits forming part of the floor of the DNA-binding (active center) cleft,
      and revealed a slight inward movement of the protein domain surrounding the
      cleft. Surface plasmon resonance measurements showed that Rpb4 and Rpb7 stabilize
      a minimal pre-initiation complex containing promoter DNA, TATA box-binding
      protein (TBP), transcription factor TFIIB and the polymerase. These findings
      suggest that Rpb4 and Rpb7 play a role in coupling the entry of DNA into the
      active center cleft to closure of the cleft. Such a role can explain why these
      subunits are necessary for promoter-specific transcription in vitro and for a
      normal stress response in vivo.

PMID- 9545248
TI  - Mechanism of translational coupling in the nifLA operon of Klebsiella pneumoniae.
AB  - The nifLA operon of Klebsiella pneumoniae encodes the sensor-activator pair
      involved in the regulation of other nif genes. Balanced synthesis of both
      proteins, which is required for correct regulation, is achieved by coupling
      translation of nifA to that of nifL. The mechanism of translational coupling at
      the nifLA operon was analysed using a specialized ribosome system, and the effect
      of substituting the natural Shine-Dalgarno of nifL or nifA for specialized Shine
      Dalgarno sequences was determined. Our results indicate that translational
      coupling occurs in this operon by a reinitiation mechanism. Additionally,
      reinitiation at the nifA can happen even in the absence of good Shine-Dalgarno
      recognition by the reinitiating ribosome, although its efficiency is lower. The
      effect of a putative translational enhancer sequence (downstream box) on
      translational coupling efficiency was also determined. Mutations that reduce the
      homology of the putative downstream box to the consensus had only a minor effect
      on nifA translation by wild-type ribosomes. However, they had a significant
      effect on nifA translation by specialized ribosomes, suggesting that recognition
      of the downstream box may compensate inefficient ribosomal interactions with the
      Shine-Dalgarno sequence.

PMID- 9545249
TI  - Tertiary structure formation in the hairpin ribozyme monitored by fluorescence
      resonance energy transfer.
AB  - The complex formed by the hairpin ribozyme and its substrate consists of two
      independently folding domains which interact to form a catalytic structure.
      Fluorescence resonance energy transfer methods permit us to study reversible
      transitions of the complex between open and closed forms. Results indicate that
      docking of the domains is required for both the cleavage and ligation reactions.
      Docking is rate-limiting for ligation (2 min-1) but not for cleavage, where
      docking (0.5 min-1) precedes a rate-limiting conformational transition or slow
      reaction chemistry. Strikingly, most modifications to the RNA (such as a G+1A
      mutation in the substrate) or reaction conditions (such as omission of divalent
      metal ion cofactors) which inhibit catalysis do so by preventing docking. This
      demonstrates directly that mutations and modifications which inhibit a step
      following substrate binding are not necessarily involved in catalysis. An
      improved kinetic description of the catalytic cycle is derived, including
      specific structural transitions.

PMID- 9545250
TI  - Dissecting RNA recombination in vitro: role of RNA sequences and the viral
      replicase.
AB  - Molecular mechanisms of RNA recombination were studied in turnip crinkle
      carmovirus (TCV), which has a uniquely high recombination frequency and non
      random crossover site distribution among the recombining TCV-associated satellite
      RNAs. To test the previously proposed replicase-driven template-switching
      mechanism for recombination, a partially purified TCV replicase preparation
      (RdRp) was programed with RNAs resembling the putative in vivo recombination
      intermediates. Analysis of the in vitro RdRp products revealed efficient
      generation of 3'-terminal extension products. Initiation of 3'-terminal extension
      occurred at or close to the base of a hairpin that was a recombination hotspot in
      vivo. Efficient generation of the 3'-terminal extension products depended on two
      factors: (i) a hairpin structure in the acceptor RNA region and (ii) a short base
      paired region formed between the acceptor RNA and the nascent RNA synthesized
      from the donor RNA template. The hairpin structure bound to the RdRp, and thus is
      probably involved in its recruitment. The probable role of the base-paired region
      is to hold the 3' terminus near the RdRp bound to the hairpin structure to
      facilitate 3'-terminal extension. These regions were also required for in vivo
      RNA recombination between TCV-associated sat-RNA C and sat-RNA D, giving crucial
      and direct support for a replicase-driven template-switching mechanism of RNA
      recombination.

PMID- 9545251
TI  - Ku80 is required for immunoglobulin isotype switching.
AB  - Isotype switching is the DNA recombination mechanism by which antibody genes
      diversify immunoglobulin effector functions. In contrast to V(D)J recombination,
      which is mediated by RAG1, RAG2 and DNA double-stranded break (DSB) repair
      proteins, little is known about the mechanism of switching. We have investigated
      the role of DNA DSB repair in switch recombination in mice that are unable to
      repair DSBs due to a deficiency in Ku80 (Ku80(-/-)). B-cell development is
      arrested at the pro-B cell stage in Ku80(-/-) mice because of abnormalities in
      V(D)J recombination, and there are no mature B cells. To reconstitute the B-cell
      compartment in Ku80(-/-) mice, pre-rearranged VB1-8 DJH2 (mu i) and V3-83JK2
      (kappa i) genes were introduced into the Ku80(-/-) background (Ku80(-/-)mu
      i/+kappa i/+). Ku80(-/-)mu i/+ kappai/+ mice develop mature mIgM+ B cells that
      respond normally to lipopolysaccharide (LPS) or LPS plus interleukin-4 (IL-4) by
      producing specific germline Ig constant region transcripts and by forming switch
      region-specific DSBs. However, Ku80(-/-)mu i/+kappa i/+ B cells are unable to
      produce immunoglobulins of secondary isotypes, and fail to complete switch
      recombination. Thus, Ku80 is essential for switch recombination in vivo,
      suggesting a significant overlap between the molecular machinery that mediates
      DNA DSB repair, V(D)J recombination and isotype switching.

PMID- 9545252
TI  - Regulation of DNA replication and repair proteins through interaction with the
      front side of proliferating cell nuclear antigen.
AB  - The DNA polymerase accessory factor proliferating cell nuclear antigen (PCNA) has
      been caught in interaction with an ever increasing number of proteins. To
      characterize the sites and functions of some of these interactions, we
      constructed four mutants of human PCNA and analysed them in a variety of assays.
      By targeting loops on the surface of the PCNA trimer and changing three or four
      residues at a time to alanine, we found that a region including part of the
      domain-connecting loop of PCNA and loops on one face of the trimer, close to the
      C-termini, is involved in binding to all of the following proteins: DNA
      polymerase delta, replication factor C, the flap endonuclease Fen1, the cyclin
      dependent kinase inhibitor p21 and DNA ligase I. An inhibition of DNA ligation
      caused by the interaction of PCNA with DNA ligase I was found, and we show that
      DNA ligase I and Fen1 can inhibit DNA synthesis by DNA polymerase delta/PCNA. We
      demonstrate that PCNA must be located below a 5' flap on a forked template to
      stimulate Fen1 activity, and considering the interacting region on PCNA for Fen1,
      this suggests an orientation for PCNA during DNA replication with the C-termini
      facing forwards, in the direction of DNA synthesis.

PMID- 9545253
TI  - Initiation of DNA replication at CpG islands in mammalian chromosomes.
AB  - CpG islands are G+C-rich regions approximately 1 kb long that are free of
      methylation and contain the promoters of many mammalian genes. Analysis of in
      vivo replication intermediates at three hamster genes and one human gene showed
      that the CpG island regions, but not their flanks, were present in very short
      nascent strands, suggesting that they are replication origins (ORIs). CpG island
      like fragments were enriched in a population of short nascent strands from human
      erythroleukaemic cells, suggesting that islands constitute a significant fraction
      of endogenous ORIs. Correspondingly, bulk CpG islands were found to replicate
      coordinately early in S phase. Our results imply that CpG islands are initiation
      sites for both transcription and DNA replication, and may represent genomic
      footprints of replication initiation.

PMID- 9545254
TI  - Devoted to the lagging strand-the subunit of DNA polymerase III holoenzyme
      contacts SSB to promote processive elongation and sliding clamp assembly.
AB  - Escherichia coli DNA polymerase III holoenzyme contains 10 different subunits
      which assort into three functional components: a core catalytic unit containing
      DNA polymerase activity, the beta sliding clamp that encircles DNA for processive
      replication, and a multisubunit clamp loader apparatus called gamma complex that
      uses ATP to assemble the beta clamp onto DNA. We examine here the function of the
      psi subunit of the gamma complex clamp loader. Omission of psi from the
      holoenzyme prevents contact with single-stranded DNA-binding protein (SSB) and
      lowers the efficiency of clamp loading and chain elongation under conditions of
      elevated salt. We also show that the product of a classic point mutant of SSB,
      SSB-113, lacks strong affinity for psi and is defective in promoting clamp
      loading and processive replication at elevated ionic strength. SSB-113 carries a
      single amino acid replacement at the penultimate residue of the C-terminus,
      indicating the C-terminus as a site of interaction with psi. Indeed, a peptide of
      the 15 C-terminal residues of SSB is sufficient to bind to psi. These results
      establish a role for the psi subunit in contacting SSB, thus enhancing the clamp
      loading and processivity of synthesis of the holoenzyme, presumably by helping to
      localize the holoenzyme to sites of SSB-coated ssDNA.

PMID- 9545255
TI  - Interaction of Drosophila inhibitors of apoptosis with thick veins, a type I
      serine/threonine kinase receptor for decapentaplegic.
AB  - Decapentaplegic (Dpp) is a Drosophila member of bone morphogenetic proteins,
      which belong to the transforming growth factor-beta superfamily. Members of this
      family regulate a variety of biological processes such as cell proliferation,
      morphogenesis, immune response, and apoptosis. Dpp plays a critical role in many
      aspects of Drosophila development. Members of the transforming growth factor-beta
      superfamily bind to two different types of serine/threonine kinase receptors,
      termed type I and type II. Type I receptors act as downstream components of type
      II receptors in the receptor complexes. Therefore, intracellular proteins that
      interact with the type I receptors are likely to play important roles in
      signaling. Several proteins have been identified through protein-protein
      interaction screenings. We identified Drosophila inhibitor of apoptosis (DIAP) 1
      as an interacting protein of a Dpp type I receptor, Thick veins (Tkv). DIAP1
      associates with Tkv in vivo. The binding region in DIAP1 is mapped to its C
      terminal RING finger region. DIAP2, another Drosophila member of the inhibitor of
      apoptosis protein family, also interacts with Tkv in vivo. These data suggest
      that DIAP1 and DIAP2 may be involved, possibly as negative regulators, in the Dpp
      signaling pathway, which leads to cell apoptosis.

PMID- 9545256
TI  - Caspase-3 is required for DNA fragmentation and morphological changes associated
      with apoptosis.
AB  - Interleukin 1beta-converting enzyme-like proteases (caspases) are crucial
      components of cell death pathways. Among the caspases identified, caspase-3
      stands out because it is commonly activated by numerous death signals and cleaves
      a variety of important cellular proteins. Studies in caspase-3 knock-out mice
      have shown that this protease is essential for brain development. To investigate
      the requirement for caspase-3 in apoptosis, we took advantage of the MCF-7 breast
      carcinoma cell line, which we show here has lost caspase-3 owing to a 47-base
      pair deletion within exon 3 of the CASP-3 gene. This deletion results in the
      skipping of exon 3 during pre-mRNA splicing, thereby abrogating translation of
      the CASP-3 mRNA. Although MCF-7 cells were still sensitive to tumor necrosis
      factor (TNF)- or staurosporine-induced apoptosis, no DNA fragmentation was
      observed. In addition, MCF-7 cells undergoing cell death did not display some of
      the distinct morphological features typical of apoptotic cells such as shrinkage
      and blebbing. Introduction of the CASP-3 gene into MCF-7 cells resulted in DNA
      fragmentation and cellular blebbing following TNF treatment. These results
      indicate that although caspase-3 is not essential for TNF- or staurosporine
      induced apoptosis, it is required for DNA fragmentation and some of the typical
      morphological changes of cells undergoing apoptosis.

PMID- 9545257
TI  - A calcium-dependent tyrosine kinase splice variant in human monocytes. Activation
      by a two-stage process involving adherence and a subsequent intracellular signal.
AB  - Freshly isolated human monocytes do not express p125(FAK) but upon adherence to
      substrata activate the highly related calcium-dependent tyrosine kinase (CADTK),
      also known as Pyk2, CAKbeta, RAFTK, and FAK2. The monocyte CADTK was 5 kDa
      smaller than protein from epithelial cells; isolation and sequencing of the
      monocyte CADTK cDNA revealed a predicted 42-amino acid deletion between the two
      proline-rich domains of the enzyme. The nucleic acid sequence suggests that the
      deletion is caused by alternative RNA splicing. This species was also found in T
      and B lymphocytes and appears to be the predominant form of cytoskeletal
      associated tyrosine kinase in non-neoplastic, circulating, hematopoietic cells.
      CADTK was not activated when monocytes maintained in suspension were treated with
      agents that produce an intracellular calcium (thapsigargin) or protein kinase C
      (phorbol 12-myristate 13-acetate) signal including a chemokine, RANTES, that
      binds to the HIV co-receptor, CCK5. In contrast, monocyte adherence to tissue
      culture plastic-stimulated CADTK tyrosine phosphorylation, a process that was
      enhanced by thapsigargin, phorbol 12-myristate 13-acetate, and RANTES but that
      was completely blocked by preincubation with cytochalasin D. When compared with
      plastic, adherence to fibronectin- or collagen-coated surfaces produced only
      minimal CADTK activation but permitted significant stimulation by added
      thapsigargin. These data suggest that in a cell type that lacks p125(FAK), CADTK
      plays an early role in post-adherence signaling. Its activation involves two
      stages, cytoskeletal engagement, which is permissive, and co-stimulatory signals
      (calcium or protein kinase C) generated by extensive cell surface engagement,
      agonists, or inflammatory chemokines.

PMID- 9545258
TI  - A novel protein distinguishes between quiescent and activated forms of the type I
      transforming growth factor beta receptor.
AB  - Transforming growth factor beta (TGFbeta) signal transduction is mediated by two
      receptor Ser/Thr kinases acting in series, type II TGFbeta receptor (TbetaR-II)
      phosphorylating type I TGFbeta receptor (TbetaR-I). Because the failure of
      interaction cloning, thus far, to identify bona fide TbetaR-I substrates might
      reasonably have been due to the use of inactive TbetaR-I as bait, we sought to
      identify molecules that interact specifically with active TbetaR-I, employing the
      triple mutation L193A,P194A,T204D in a yeast two-hybrid system. The Leu-Pro
      substitutions prevent interaction with FK506-binding protein 12 (FKBP12), whose
      putative function in TGFbeta signaling we have previously disproved; the charge
      substitution at Thr204 constitutively activates TbetaR-I. Unlike previous screens
      using wild-type TbetaR-I, where FKBP12 predominated, none of the resulting
      colonies encoded FKBP12. A novel protein was identified, TbetaR-I-associated
      protein-1 (TRAP-1), that interacts in yeast specifically with mutationally
      activated TbetaR-I, but not wild-type TbetaR-I, TbetaR-II, or irrelevant
      proteins. In mammalian cells, TRAP-1 was co-precipitated only by mutationally
      activated TbetaR-I and ligand-activated TbetaR-I, but not wild-type TbetaR-I in
      the absence of TGFbeta. The partial TRAP-1 protein that specifically binds these
      mutationally and ligand-activated forms of TbetaR-I can inhibit signaling by the
      native receptor after stimulation with TGFbeta or by the constitutively activated
      receptor mutation, as measured by a TGFbeta-dependent reporter gene. Thus, TRAP-1
      can distinguish activated forms of the receptor from wild-type receptor in the
      absence of TGFbeta and may potentially have a functional role in TGFbeta
      signaling.

PMID- 9545259
TI  - Urea transporter UT3 functions as an efficient water channel. Direct evidence for
      a common water/urea pathway.
AB  - A family of molecular urea transporters (UTs) has been identified whose members
      appear to have an exceptionally high transport turnover rate. To test the
      hypothesis that urea transport involves passage through an aqueous channel,
      osmotic water permeability was measured in Xenopus oocytes expressing UTs. The
      UT3 class of urea transporters functioned as efficient water channels.
      Quantitative measurement of single channel water permeability (pf) using epitope
      tagged rat UTs gave pf (in cm3/s x 10(-14)) of 0.14 +/- 0.11 (UT2) and 1.4 +/-
      0.2 (UT3), compared with 6.0 and 2.3 for water channels AQP1 and AQP3,
      respectively. Relative single channel urea permeabilities (purea) were 1.0 (UT2),
      0.44 (UT3), and 0.0 (AQP1). UT3-mediated water and urea transport were weakly
      temperature-dependent (activation energy <4 kcal/mol), inhibited > 75% by the
      urea transport inhibitor 1,3-dimethylthiourea, but not inhibited by the water
      transport inhibitor HgCl2. To test for a common water/urea pore, the urea
      reflection coefficient (sigmaurea) was measured by independent induced osmosis
      and solvent drag methods. In UT3-expressing oocytes, the time course of oocyte
      volume in response to different urea gradients (induced osmosis) gave sigmaurea
      approximately 0.3 for the UT3 pathway, in agreement with sigmaurea determined by
      the increase in uptake of [14C]urea during osmotic gradient-induced oocyte
      swelling (solvent drag). In oocytes of comparable water and urea permeability
      coexpressing AQP1 (permeable to water, not urea) and UT2 (permeable to urea, not
      water), sigmaurea = 1. These results indicate that UT3 functions as a urea/water
      channel utilizing a common aqueous pathway. The water transporting function and
      low urea reflection coefficient of UT3 in vasa recta may be important for the
      formation of a concentrated urine by countercurrent exchange in the kidney.

PMID- 9545260
TI  - The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol
      esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways.
AB  - Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key
      role in the mechanism and regulation of translation. It may be regulated through
      its own phosphorylation and through inhibitory binding proteins (4E-BPs), which
      modulate its availability for initiation complex assembly. eIF4E phosphorylation
      is enhanced by phorbol esters. We show, using specific inhibitors, that this
      involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling
      pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor
      necrosis factor-alpha and interleukin-1beta also cause increased phosphorylation
      of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580.
      These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase,
      Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also
      stimulate p38 MAP kinase and increase Mnk1 activity, do not increase
      phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E
      BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro,
      which may explain the absence of an increase in eIF4E phosphorylation under these
      conditions.

PMID- 9545261
TI  - Two novel odorant receptor families expressed in spermatids undergo 5'-splicing.
AB  - We report the identification of two novel families of odorant receptor (OdR)-like
      proteins, termed spermatid chemoreceptors (SCRs), in rat spermatids of the
      testis. The full-length genomic clones encode seven transmembrane domain
      receptors that share 35-40% identity with certain OdRs and are among the most
      divergent members of the OdR superfamily based on phylogenetic analysis. RNase
      protection assays and in situ hybridization studies confirmed the expression of
      SCRs in spermatids, the post-meiotic, differentiating cell population in the
      testis. SCR transcripts were undetectable in the prepubertal testis but were
      readily identified in spermatids of sexually maturing and mature testis. Rapid
      amplification of cDNA end-polymerase chain reaction and genomic clone sequencing
      led to the discovery that SCRs are spliced upstream of their presumptive starting
      methionines. 5'-Splicing of OdRs may regulate the expression of functional
      chemoreceptors.

PMID- 9545262
TI  - Heterochromatin organization of a natural yeast telomere. Changes of nucleosome
      distribution driven by the absence of Sir3p.
AB  - We have defined the in vivo heterochromatin structure of the left telomere of
      Saccharomyces cerevisiae chromosome III (LIII). Analysis of heterochromatin of a
      single telomere was so far lacking, due to the difficulties intrinsic to the
      highly repetitive nature of telomeric sequences. In LIII, the terminal (C1-3A)n
      repetitive sequences are followed by a complete X element and by the single copy
      Ty5-1 retrotransposon. Both the telosome and the X element exhibit overall
      resistance to micrococcal nuclease digestion reflecting their tight chromatin
      structure organization. The X element contains protein complexes and irregularly
      distributed but well localized nucleosomes. In contrast, a regular array of
      phased nucleosomes is associated with the promoter region of Ty5-1 and with the
      more centromere-proximal sequences. The lack of a structural component of yeast
      telomeres, the SIR3 protein, does not alter the overall tight organization of the
      X element but causes a nucleosome rearrangement within the promoter region of Ty5
      1 and releases Ty5-1 silencing. Thus, Sir3p links the modification of the
      heterochromatin structure with loss of transcriptional silencing.

PMID- 9545263
TI  - FcgammaRI coupling to phospholipase D initiates sphingosine kinase-mediated
      calcium mobilization and vesicular trafficking.
AB  - Aggregation of receptors specific for the constant region of immunoglobulin G
      activates a repertoire of monocyte responses that can lead ultimately to targeted
      cell killing via antibody-directed cellular cytotoxicity. The high affinity
      receptor, FcgammaRI, contains no recognized signaling motif in its cytoplasmic
      tail but rather utilizes the gamma-chain of FcepsilonRI as an accessory molecule
      to recruit tyrosine kinases for signal transduction. We show here that, in a
      human monocytic cell line primed with interferon-gamma, FcgammaRI mobilizes
      intracellular calcium stores using a novel pathway that involves tyrosine kinase
      coupling to phospholipase D and resultant downstream activation of sphingosine
      kinase. Moreover, FcgammaRI is not coupled to phospholipase C; hence, calcium
      release from intracellular stores occurred in the absence of any measurable rise
      in inositol triphosphate. Finally, as this novel activation pathway is also shown
      to be responsible for mediating the vesicular trafficking of internalized immune
      complexes for degradation, it is likely to play a key role in controlling
      intracellular events triggered by FcgammaRI.

PMID- 9545264
TI  - Converse modulation of IRP1 and IRP2 by immunological stimuli in murine RAW 264.7
      macrophages.
AB  - Iron regulatory proteins (IRP1 and IRP2) are two cytoplasmic RNA-binding proteins
      that control iron metabolism in mammalian cells. Both IRPs bind to specific
      sequences called iron-responsive elements (IREs) located in the 3' or 5'
      untranslated regions of several mRNAs, in particular mRNA encoding ferritin and
      transferrin receptor. In this study, we followed in parallel the in vivo
      regulation of the two IRPs in physiologically stimulated macrophages. We show
      that stimulation of mouse RAW 264.7 macrophage-like cells increased IRP1 IRE
      binding activity 4-fold, whereas IRP2 activity decreased 2-fold 8 h after
      interferon-gamma/lipopolysaccharide treatment. Decrease in IRP2 was not due to
      nitric oxide (NO) production and did not require de novo protein synthesis. Our
      data therefore indicate that the two IRPs can be conversely regulated in response
      to the same stimulus. In addition, the effect of endogenously produced NO on IRP1
      was further characterized in an activated macrophage/target cell system. We show
      that NO acts as an intercellular signal to increase IRP1 activity in adjacent
      cells. As the effect was detectable within 1 h and did not require de novo
      protein synthesis, this result supports a direct action of NO on IRP1.

PMID- 9545265
TI  - Stimulation of replication efficiency of a chromatin template by chromosomal
      protein HMG-17.
AB  - The effect of chromosomal protein HMG-17 on the replication of a chromatin
      template was studied with minichromosomes containing the SV40 origin of
      replication. The minichromosomes were assembled from M13 DNA in Xenopus egg
      extracts in either the absence or presence of HMG-17. Structural data show that
      HMG-17 was efficiently incorporated into the chromatin and induced an extended
      chromatin structure. Using an in vitro SV40 replication system, we find that
      minichromosomes containing HMG-17 replicate with higher efficiency than
      minichromosomes deficient of HMG-17. The replicational potential of chromatin was
      enhanced only when HMG-17 was incorporated into the template during, but not
      after, chromatin assembly. HMG-17 stimulated replication only from a chromatin
      template, but not from protein-free DNA. Thus, HMG-17 protein enhances the rate
      of replication of a chromatin template by unfolding the higher order chromatin
      structure and increasing the accessibility of target sequences to components of
      the replication machinery.

PMID- 9545266
TI  - Interactions of chaperone alpha-crystallin with the molten globule state of
      xylose reductase. Implications for reconstitution of the active enzyme.
AB  - alpha-Crystallin is a multimeric protein that has been shown to function as a
      molecular chaperone. Present investigations were undertaken to understand its
      mechanism of chaperoning. For this functional in vitro analysis of alpha
      crystallin we used xylose reductase (XR) from Neurospora crassa as the model
      system. Denaturation studies using the structure-perturbing agent guanidinium
      chloride indicated that XR folds through a partially folded state that resembles
      the molten globule. Fluorescence and delay experiments revealed that alpha
      crystallin interacts with the molten globule state of XR (XR-m) and prevents its
      aggregation. Cold lability of alpha-crystallin.XR-m interaction was revealed by
      temperature shift experiments implicating the involvement of hydrophobic
      interactions in the formation of the complex. Reconstitution of active XR was
      observed on cooling the alpha-crystallin.XR-m complex to 4 degrees C or on
      addition of ATP at 37 degrees C. ATP hydrolysis is not a prerequisite for XR
      release since the nonhydrolyzable analogue 5'-adenylyl imidodiphosphate (AMP-PNP)
      was capable of reconstitution of active XR. Experimental evidence has been
      provided for temperature- and ATP-mediated structural changes in the alpha
      crystallin.XR-m complex that shed some light on the mechanism of reconstitution
      of active XR by this chaperone. The relevance of our finding to the role of alpha
      crystallin in vivo is discussed.

PMID- 9545268
TI  - Effects of FK506-binding protein 12 and FK506 on autophosphorylation of epidermal
      growth factor receptor.
AB  - FK506-binding proteins and cyclophilins are intracellular proteins that express
      peptidylproline cis-trans-isomerase (PPIase) activity. The effects of FK506
      binding protein 12 (FKBP12) and the cyclophilins 18 and 23 on autophosphorylation
      of the epidermal growth factor (EGF) receptor prepared from plasma membranes of
      the human epidermoid cell line A431 have been investigated. Whereas FKBP12
      inhibited EGF receptor tyrosine kinase activity in a concentration-dependent
      manner, the cyclophilins did not affect autophosphorylation. In contrast to the
      wild-type enzyme, several variants of FKBP12 with greatly reduced PPIase activity
      were unable to suppress EGF receptor tyrosine kinase significantly. Pervanadate
      an inhibitor of protein tyrosine phosphatases, abolished the effect of FKBP12 on
      EGF receptor autophosphorylation. Finally, FK506 and rapamycin, which are known
      to block the PPIase activity of FKBP12, induced a significant stimulation of EGF
      receptor autophosphorylation in intact A431 cells suggesting suppression of EGF
      receptor autophosphorylation by intracellular FKBP12 in vivo. Taken together the
      data point to an inhibitory function of FKBP12 in EGF receptor signaling,
      possibly induced by stimulation of a protein tyrosine phosphatase coupled to the
      EGF receptor. Both PPIase activity and substrate specificity of FKBP12 seem to be
      indispensable for this effect.

PMID- 9545267
TI  - dGNaC1, a gonad-specific amiloride-sensitive Na+ channel.
AB  - Amiloride-sensitive sodium channels have been implicated in reproductive and
      early developmental processes of several species. These include the fast block of
      polyspermy in Xenopus oocytes that follows the sperm binding to the egg or
      blastocoel expansion in mammalian embryo. We have now identified a gene called
      dGNaC1 that is specifically expressed in the gonads and early embryo in
      Drosophila melanogaster. The corresponding protein belongs to the superfamily of
      cationic channels blocked by amiloride that includes Caenorhabditis elegans
      degenerins, the Helix aspersa FMRF-amide ionotropic receptor (FaNaC), the
      mammalian epithelial Na+ channel (ENaC), and acid-sensing ionic channels (ASIC,
      DRASIC, and MDEG). Expression of dGNaC1 in Xenopus oocytes generates a
      constitutive current that does not discriminate between Na+ and Li+, but is
      selective for Na+ over K+. This current is blocked by amiloride (IC50 = 24
      microM), benzamil (IC50 = 2 microM), and ethylisopropyl amiloride (IC50 = 49
      microM). These properties are clearly different from those obtained after
      expression of the previously cloned members of this family, including ENaC and
      the human alphaENaC-like subunit, deltaNaC. Interestingly, the pharmacology of
      dGNaC1 is not very different from that found for the Na+ channel characterized in
      rabbit preimplantation embryos. We postulate that this channel may participate in
      gametogenesis and early embryonic development in Drosophila.

PMID- 9545269
TI  - Two efficiency elements flanking the editing site of cytidine 6666 in the
      apolipoprotein B mRNA support mooring-dependent editing.
AB  - Normally, apolipoprotein B (apoB) mRNA editing deaminates a single cytidine
      (C6666) in apoB mRNA. However, when the catalytic subunit of the editing enzyme
      complex, APOBEC-1, was overexpressed in transgenic mice and rabbits, numerous
      cytidines in the apoB mRNA and in a novel mRNA, NAT1, were aberrantly
      hyperedited, and the animals developed liver dysplasia and hepatocellular
      carcinomas. To identify the RNA motifs in the apoB mRNA that support
      physiological editing and those that support aberrant hyperediting, we
      constructed rabbit apoB RNA substrates and tested them in vitro for physiological
      editing and hyperediting. Three previously unrecognized RNA elements that are
      critical for efficient physiological editing at C6666 were identified. In concert
      with the mooring sequence (6671-6681), the 5' efficiency element (6609-6628), an
      A-rich region (6629-6640), and the 3' efficiency element (6717-6747) increased
      editing at C6666. The 5' efficiency element was the most potent, elevating
      physiological editing to wild-type levels in combination with the mooring
      sequence. The 3' efficiency element was somewhat less important but increased
      physiological editing to levels approaching wild type. These elements encompass
      139 nucleotides on the apoB RNA transcript and are sufficient for editing with
      the efficiency of full-length apoB mRNA. Furthermore, a distal downstream apoB
      region (6747-6824) may function as a recognition element in the apoB mRNA.
      Hyperediting at C6802 in the rabbit apoB mRNA is mediated by RNA elements similar
      to those required for normal physiological editing at C6666. Similarly sized
      upstream and downstream flanking regions of C6802 are necessary for hyperediting
      in combination with a degenerate mooring sequence.

PMID- 9545270
TI  - Stabilization of alpha-synuclein secondary structure upon binding to synthetic
      membranes.
AB  - alpha-Synuclein is a highly conserved presynaptic protein of unknown function. A
      mutation in the protein has been causally linked to Parkinson's disease in
      humans, and the normal protein is an abundant component of the intraneuronal
      inclusions (Lewy bodies) characteristic of the disease. alpha-Synuclein is also
      the precursor to an intrinsic component of extracellular plaques in Alzheimer's
      disease. The alpha-synuclein sequence is largely composed of degenerate 11
      residue repeats reminiscent of the amphipathic alpha-helical domains of the
      exchangeable apolipoproteins. We hypothesized that alpha-synuclein should
      associate with phospholipid bilayers and that this lipid association should
      stabilize an alpha-helical secondary structure in the protein. We report that
      alpha-synuclein binds to small unilamellar phospholipid vesicles containing
      acidic phospholipids, but not to vesicles with a net neutral charge. We further
      show that the protein associates preferentially with vesicles of smaller diameter
      (20-25 nm) as opposed to larger (approximately 125 nm) vesicles. Lipid binding is
      accompanied by an increase in alpha-helicity from 3% to approximately 80%. These
      observations are consistent with a role in vesicle function at the presynaptic
      terminal.

PMID- 9545271
TI  - Deletion and site-directed mutagenesis of the ATP-binding motif (P-loop) in the
      bifunctional murine ATP-sulfurylase/adenosine 5'-phosphosulfate kinase enzyme.
AB  - The P-loop is a common motif found in ATP- and GTP-binding proteins. The recently
      cloned murine ATP-sulfurylase/adenosine 5'-phosphosulfate (APS) kinase contains a
      P-loop (residues 59-66) in the APS kinase portion of the bifunctional protein. A
      series of enzymatic assays covering the multiplicity of functions of this unique
      protein (reverse ATP-sulfurylase, APS kinase, and an overall assay) were used to
      determine the effect of deleting or altering specific residues constituting this
      motif. In addition to the full-length cDNA construct (1MSK), two deletion mutants
      that progressively shortened the N terminus by 34 amino acids (2MSK) and 70 amino
      acids (3MSK) were designed to examine the effects of translation initiation
      before (2MSK) and after (3MSK) the P-loop. The 2MSK protein possessed sulfurylase
      and kinase activity equivalent to the full-length construct, but 3MSK exhibited
      no kinase activity and reduced sulfurylase activity. In light of the evident
      importance of this motif, a number of site-directed mutants were designed to
      investigate the contribution of key residues. Mutation of a highly conserved
      lysine in the P-loop to alanine (K65A) or arginine (K65R) or the following
      threonine (T66A) to alanine ablated APS kinase activity while leaving ATP
      sulfurylase activity intact. Three mutations (G59A, G62A, and G64A) addressed the
      role of the conserved glycines as follows: G64A showed diminished APS kinase
      activity only, whereas G62A had no effect on either activity. G59A caused a
      significant decrease in ATP-sulfurylase activity without effect on APS kinase
      activity. A series of highly conserved flanking cysteines (Cys-53, Cys-77, and
      Cys-83) were mutated to alanine, but none of these mutations showed any effect on
      either enzyme activity.

PMID- 9545272
TI  - Genomic organization, chromosomal mapping, and promoter analysis of the mouse
      dentin sialophosphoprotein (Dspp) gene, which codes for both dentin sialoprotein
      and dentin phosphoprotein.
AB  - Our laboratory has reported that two major noncollagenous dentin proteins, dentin
      sialoprotein and dentin phosphoprotein, are specific cleavage products of a
      larger precursor protein termed dentin sialophosphoprotein (MacDougall, M.,
      Simmons, D., Luan, X., Nydegger, J., Feng, J. Q., and Gu, T. T. (1997) J. Biol.
      Chem. 272:835-842). To confirm our single gene hypothesis and initiate in vitro
      promoter studies, we have characterized the structural organization of the mouse
      dentin sialophosphoprotein gene. This gene has a transcription unit of
      approximately 9.4 kilobase pairs and is organized into 5 exons and 4 introns.
      Exon 1 contains a noncoding 5' sequence, and exon 2 contains the transcriptional
      start site, signal peptide, and first two amino acids of the NH2 terminus. Exons
      3 and 4 contain coding information for 29 and 314 amino acids, respectively. The
      remainder of the coding information and the untranslated 3' region are contained
      in exon 5. Chromosomal mapping localized the gene to mouse chromosome 5q21 in
      close proximity to other dentin/bone matrix genes. Computer analysis of the
      promoter proximal 1.6-kilobase pair sequence revealed a number of potentially
      important cis-regulatory sequences; these include the recognition elements of AP
      1, AP-2, Msx-1, serum response elements, SP-1, and TCF-1. In vitro studies showed
      that the DSPP promoter is active in an odontoblast cell line, MO6-G3, with basal
      activity mapped to -95 bp. Two potential enhancer and suppresser elements were
      identified in the regions between -1447 and -791 bp and -791 and -95 bp,
      respectively. The structural organization of the dentin sialophosphoprotein gene
      confirms our finding that both dentin sialoprotein and dentin phosphoprotein are
      encoded by a single gene with a continuous open reading frame.

PMID- 9545273
TI  - Interactions of phosducin with the subunits of G-proteins. Binding to the alpha
      as well as the betagamma subunits.
AB  - The high affinity interactions of phosducin with G-proteins involve binding of
      phosducin to the G-protein betagamma subunits. Here we have investigated whether
      phosducin interacts also with G-protein alpha subunits. Interactions of phosducin
      with the individual subunits of Go were measured by retaining phosducin-G-protein
      subunit complexes on columns containing immobilized anti-phosducin antibodies.
      Both the alpha and the beta subunits of trimeric Go were specifically retained by
      the antibodies in the presence of phosducin. This binding was almost completely
      abolished for both subunits following protein kinase A-mediated phosphorylation
      of phosducin and was reduced, more for alpha than for beta subunits, by the
      stable GTP analog guanosine 5'-(3-O-thio)triphosphate. Isolated alphao was also
      retained on the columns in the presence of phosducin but not in the presence of
      protein kinase A-phosphorylated phosducin. Likewise, purified G-protein betagamma
      subunit complexes as well as purified alpha subunits of Go and Gt were
      precipitated together with His6-tagged phosducin with nickel-agarose; this co
      precipitation occurred concentration-dependently, with apparent affinities for
      phosducin of 55 nM (Gbetagamma), 110 nM (alphao), and 200 nM (alphat). In
      functional experiments, the steady state GTPase activity of isolated alphao was
      inhibited by phosducin by approximately 60% with an IC50 value of approximately
      300 nM, whereas the GTPase activity of trimeric Go was inhibited by approximately
      90% with an IC50 value of approximately 10 nM. Phosducin did not inhibit the GTP
      hydrolytic activity of isolated alphao as measured by single-turnover assays, but
      it inhibited the release of GDP from alphao; the rate constant of GDP release was
      decreased approximately 40% by 500 nM phosducin, and the inhibition occurred with
      an IC50 value for phosducin of approximately 100 nM. These data suggest that
      phosducin binds with high affinity to G-protein betagamma subunits and with lower
      affinity to G-protein alpha subunits. We propose that the alpha subunit-mediated
      effects of phosducin might increase both the extent and the rapidity of its
      inhibitory effects compared with an action via the betagamma subunit complex
      alone.

PMID- 9545274
TI  - Amino acid residues that define both the isoprenoid and CAAX preferences of the
      Saccharomyces cerevisiae protein farnesyltransferase. Creating the perfect
      farnesyltransferase.
AB  - Studies of the yeast protein farnesyltransferase (FTase) have shown that the
      enzyme preferentially farnesylates proteins ending in CAAX (C = cysteine, A =
      aliphatic residue, X = cysteine, serine, methionine, alanine) and to a lesser
      degree CAAL. Furthermore, like the type I protein geranylgeranyltransferase
      (GGTase-I), FTase can also geranylgeranylate methionine- and leucine-ending
      substrates both in vitro and in vivo. Substrate overlap of FTase and GGTase I has
      not been determined to be biologically significant. In this study, specific
      residues that influence the substrate preferences of FTase have been identified
      using site-directed mutagenesis. Three of the mutations altered the substrate
      preferences of the wild type enzyme significantly. The ram1p-74D FTase
      farnesylated only Ras-CIIS and not Ras-CII(M,L), and it geranylgeranylated all
      three substrates as well or better than wild type. The ram1p-206DDLF FTase
      farnesylated Ras-CII(S,M,L) at wild type levels but could no longer
      geranylgeranylate the Ras-CII(M,L) substrates. The ram1p-351FSKN FTase
      farnesylated Ras-CIIS and Ras-CIIM but not Ras-CIIL. The ram1p-351FSKN FTase was
      not capable of geranylgeranylating the Ras-CII(M,L) substrates, giving this
      mutant the attributes of the dogmatic FTase that only farnesylates non-leucine
      ending CAAX substrates and does not geranylgeranylate any substrate. These
      results suggest that the isoprenoid and protein substrate specificities of FTase
      are interrelated. The availability of a mutant FTase that lacked substrate
      overlap with the protein GGTase-I made possible an analysis of the role of
      substrate overlap in normal cellular processes of yeast, such as mating and
      growth at elevated temperatures. Our findings suggest that neither farnesylation
      of leucine-ending CAAX substrates nor geranylgeranylation by the FTase is
      necessary for these cellular processes.

PMID- 9545275
TI  - The importance of two conserved arginine residues for catalysis by the ras GTPase
      activating protein, neurofibromin.
AB  - Ras proteins are guanine-nucleotide binding proteins that have a low intrinsic
      GTPase activity that is enhanced 10(5)-fold by the GTPase-activating proteins
      (GAPs) p120-GAP and neurofibromin. Comparison of the primary sequences of RasGAPs
      shows two invariant arginine residues (Arg1276 and Arg1391 of neurofibromin). In
      this study, site-directed mutagenesis was used to change each of these residues
      in the catalytic domain of neurofibromin (NF1-334) to alanine. The ability of the
      mutant proteins to bind to Ras.GTP and to stimulate their intrinsic GTPase rate
      was then determined by kinetic methods under single turnover conditions using a
      fluorescent analogue of GTP. The separate contributions of each of these residues
      to catalysis and binding affinity to Ras were measured. Both the R1276A and the
      R1391A mutant NF1-334 proteins were 1000-fold less active than wild-type NF1-334
      in activating the GTPase when measured at saturating concentrations. In contrast,
      there was only a minor effect of either mutation on NF1-334 affinity for wild
      type Ha-Ras. These data are consistent with both arginines being required for
      efficient catalysis. Neither arginine is absolutely essential, because the mutant
      NF1-334 proteins increase the intrinsic Ras.GTPase by at least 100-fold. The
      roles of Arg1276 and Arg1391 in neurofibromin are consistent with proposals based
      on the recently published x-ray structure of p120-GAP complexed with Ras.

PMID- 9545276
TI  - Characterization of a nucleoside/proton symporter in procyclic Trypanosoma brucei
      brucei.
AB  - Adenosine transport at 22 degrees C in procyclic forms of Trypanosoma brucei
      brucei was investigated using an oil-inhibitor stop procedure for determining
      initial rates of adenosine uptake in suspended cells. Adenosine influx was
      mediated by a single high affinity transporter (Km 0.26 +/- 0.02 microM, Vmax
      0.63 +/- 0.18 pmol/10(7) cells s-1). Purine nucleosides, with the exception of
      tubercidin (7-deazaadenosine), and dipyridamole inhibited adenosine influx (Ki
      0.18-5.2 microM). Purine nucleobases and pyrimidine nucleosides and nucleobases
      had no effect on adenosine transport. This specificity of the transporter appears
      to be similar to the previously described P1 adenosine transporter in bloodstream
      forms of trypanosomes. Uptake of adenosine was Na+-independent, but ionophores
      reducing the membrane potential and/or the transmembrane proton gradient
      (monitored with the fluorescent probes bis-(1,3-diethylthiobarbituric acid)
      trimethine oxonol and 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein
      acetoxymethyl ester, respectively) inhibited adenosine transport. Similarly, an
      increase in extracellular pH from 7.3 to 8.0 reduced adenosine influx by 30%. A
      linear correlation was demonstrated between the rate of adenosine transport and
      the protonmotive force. Adenosine uptake was accompanied by a proton influx in
      base-loaded cells and was also shown to be electrogenic. These combined results
      indicate that transport of adenosine in T. brucei brucei procyclics is
      protonmotive force-driven and strongly suggest that the adenosine transporter
      functions as an H+ symporter.

PMID- 9545277
TI  - Regulation of mammary differentiation by extracellular matrix involves protein
      tyrosine phosphatases.
AB  - Extracellular matrix and growth factors cooperate to regulate signaling pathways
      and gene transcription in adherent cells. However, the mechanism of extracellular
      matrix signaling is poorly defined. In mammary gland, the expression of milk
      protein genes is controlled by cross-talk between signals derived from the
      basement membrane protein, laminin, and the lactogenic hormone, prolactin.
      Signals from basement membrane are transduced by beta1 integrins and are required
      for prolactin to activate DNA binding of the milk protein gene transcription
      factor, Stat5. Here we show that basement membrane is necessary for tyrosine
      phosphorylation of the prolactin receptor and thus directly affects cytokine
      signaling and differentiation at the level of the plasma membrane. Prolactin does
      not induce tyrosine phosphorylation of its receptor, Jak2, or Stat5 in
      nondifferentiated breast epithelia cultured on collagen I, and we show that this
      is due to a vanadate-sensitive activity that inhibits the prolactin pathway. We
      suggest that protein-tyrosine phosphatases are novel targets for regulation by
      extracellular matrix and in mammary cells represent an additional control to the
      requirement of integrins for milk protein production.

PMID- 9545278
TI  - Proteasome activation by REG molecules lacking homolog-specific inserts.
AB  - The peptidase activities of eukaryotic proteasomes are markedly activated by the
      11 S REG or PA28. The three identified REG subunits, designated alpha, beta, and
      gamma, differ significantly in sequence over a short span of 15-30 amino acids
      that we call homolog-specific inserts. These inserts were deleted from each REG
      to produce the mutant proteins REGalphaDeltai, REGbetaDeltai, and REGgammaDeltai.
      The purified recombinant proteins were then tested for their ability to
      oligomerize and activate the proteasome. Both REGalphaDeltai and REGgammaDeltai
      formed apparent heptamers and activated human red cell proteasomes to the same
      extent as their full-length counterparts. By contrast, REGbetaDeltai exhibited,
      at low protein concentrations, reduced proteasome activation when compared with
      the wild-type REGbeta protein. REGbetaDeltai was able to form hetero-oligomers
      with a single site, monomeric REGalpha mutant and with REGalphaDeltai. At low
      concentrations, the REGalphaDeltai/REGbetaDeltai hetero-oligomers stimulated the
      proteasome less than REGalpha/REGbeta oligomers formed from wild-type subunits,
      and the reduced activation by REGalphaDeltai/REGbetaDeltai was due to removal of
      the REGbeta insert, not the REGalpha insert. These studies demonstrate that the
      REGalpha and REGgamma inserts play virtually no role in oligomerization or in
      proteasome activation. By contrast, removal of REGbeta insert reduces binding of
      this subunit and REGalpha/REGbeta oligomers to proteasomes. On the whole,
      however, our findings show that REG inserts are not required for binding and
      activating the proteasome. We speculate that they serve to localize REG
      proteasome complexes within cells, possibly by binding components in endoplasmic
      reticulum membranes.

PMID- 9545279
TI  - Circadian periodicity of intestinal Na+/glucose cotransporter 1 mRNA levels is
      transcriptionally regulated.
AB  - Intestinal expression of the high affinity Na+/glucose cotransporter 1 (SGLT1),
      which absorbs dietary glucose and galactose, exhibits both circadian periodicity
      in its activity and induction by dietary carbohydrate. Because the daily
      variation in SGLT1 activity is established by the feeding schedule (whether ad
      libitum or imposed) and persists in the absence of food, this variation has been
      described as anticipatory. To delineate the mechanisms regulating SGLT1, its
      expression was examined in rats maintained in a 12-h photoperiod with free access
      to chow. SGLT1 mRNA levels varied significantly, with the maximum abundance
      occurring near the onset of dark and the minimum near the onset of light. The
      SGLT1 transcription rate was 7-fold higher in the morning (1000-1100 h) than in
      the afternoon (1600-1700 h). An element for hepatocyte nuclear factor 1 (HNF-1)
      was identified in the SGLT1 promoter that formed different complexes with small
      intestinal nuclear extracts, depending on the time when the source animal was
      killed. Serological tests indicated that HNF-1alpha was present in complexes
      throughout the day, while HNF-1beta binding exhibited circadian periodicity. We
      propose that exchange of HNF-1 dimerization partners contributes to circadian
      changes in SGLT1 transcription. Because SGLT1 mRNA levels also varied in rhesus
      monkeys (offset by approximately one-half day from rats), a similar mechanism
      appears to be present in primates.

PMID- 9545280
TI  - Solution and crystal structures of a sperm whale myoglobin triple mutant that
      mimics the sulfide-binding hemoglobin from Lucina pectinata.
AB  - The bivalve mollusc Lucina pectinata harbors sulfide-oxidizing chemoautotrophic
      bacteria and expresses a monomeric hemoglobin I, HbI, with normal O2, but
      extraordinarily high sulfide affinity. The crystal structure of aquomet Lucina
      HbI has revealed an active site with three residues not commonly found in
      vertebrate globins: Phe(B10), Gln(E7), and Phe(E11) (Rizzi, M., Wittenberg, J.
      B., Coda, A., Fasano, M., Ascenzi, P., and Bolognesi, M. (1994) J. Mol. Biol.
      244, 86-89). Engineering these three residues into sperm whale myoglobin results
      in a triple mutant with approximately 700-fold higher sulfide affinity than for
      wild-type. The single crystal x-ray structure of the aquomet derivative of the
      myoglobin triple mutant and the solution 1H NMR active site structures of the
      cyanomet derivatives of both the myoglobin mutant and Lucina HbI have been
      determined to examine further the structural origin of their unusually high
      sulfide affinities. The major differences in the distal pocket is that in the
      aquomet form the carbonyl of Gln64(E7) serves as a H-bond acceptor, whereas in
      the cyanomet form the amido group acts as H-bond donor to the bound ligand.
      Phe68(E11) is rotated approximately 90 degrees about chi2 and located
      approximately 1-2 A closer to the iron atom in the myoglobin triple mutant
      relative to its conformation in Lucina HbI. The change in orientation potentially
      eliminates the stabilizing interaction with sulfide and, together with the
      decrease in size of the distal pocket, accounts for the 7-fold lower sulfide
      affinity of the myoglobin mutant compared with that of Lucina HbI.

PMID- 9545281
TI  - Flavohemoglobin expression and function in Saccharomyces cerevisiae. No
      relationship with respiration and complex response to oxidative stress.
AB  - The yeast Saccharomyces cerevisiae contains a flavohemoglobin, encoded by the
      gene YHB1, whose function is unclear. Previous reports presented evidence that
      its maximal expression requires disruption of mitochondrial respiration and that
      it plays a role in the response to oxidative stress. We have studied the
      expression of YHB1 in respiratory deficient cells and in cells exposed to various
      compounds causing oxidative stress. Several different strains and approaches
      (spectroscopic detection of the oxygenated form of Yhb1p, beta-galactosidase
      activity of a YHB1-lacZ fusion, and Northern blot analysis) were used to
      demonstrate that YHB1 expression and Yhb1p production are not increased by
      respiration deficiency. YHB1 expression was unchanged in cells challenged with
      antimycin A or menadione, while it decreased in cells exposed to H2O2, diamide,
      dithiothreitol, and Cu2+. Transcription of YHB1 is not under the control of the
      transcriptional factor Yap1p. These results do not support a participation of
      YHB1 in the genetic response to oxidative stress. We also analyzed the growth
      phenotypes associated with altered Yhb1p production using YHB1-deleted strains
      and strains that greatly overproduced Yhb1p. Yhb1p appears to protect cells
      against the damage caused by Cu2+ and dithiothreitol, while sensitizing them to
      H2O2. Yhb1p overproduction in a glucose-6-phosphate dehydrogenase-deficient
      mutant decreased its growth rate. These data indicate that there is a complex
      relationship(s) between Yhb1p function(s) and cell defense reactions against
      various stresses.

PMID- 9545282
TI  - Functional correlation among Gal11, transcription factor (TF) IIE, and TFIIH in
      Saccharomyces cerevisiae. Gal11 and TFIIE cooperatively enhance TFIIH-mediated
      phosphorylation of RNA polymerase II carboxyl-terminal domain sequences.
AB  - Saccharomyces cerevisiae Gal11, a component of the holoenzyme of RNA polymerase
      II, interacts through its functional domains A and B with the small (Tfa2) and
      large (Tfa1) subunits of the general transcription factor (TF) IIE, respectively.
      We have recently suggested that Gal11 functions through a common pathway with
      TFIIE in transcriptional regulation (Sakurai, H., and Fukasawa, T. (1997) J.
      Biol. Chem. 272, 32663-32669). Here, we report that the activity of the TFIIH
      associated kinase, responsible for phosphorylation of the largest subunit of RNA
      polymerase II at the carboxyl-terminal domain (CTD), is enhanced cooperatively by
      Gal11 and TFIIE. The enhancement of CTD phosphorylation was observed in the
      holoenzyme of RNA polymerase II, but not in its core enzyme. The stimulatory
      effect was completely abolished in the absence of either domain B of Gal11 or the
      Tfa1 subunit of TFIIE, suggesting that the domain B-Tfa1 interaction is
      necessary, if not sufficient, for an extensive phosphorylation of the CTD by
      TFIIH. Stimulation of basal transcription by Gal11 was coupled with enhancement
      of TFIIH-catalyzed CTD phosphorylation in a cell-free transcription system,
      suggesting that Gal11 activates transcription by stimulating the CTD
      phosphorylation in the cell.

PMID- 9545283
TI  - Activation of the leukocyte NADPH oxidase by phorbol ester requires the
      phosphorylation of p47PHOX on serine 303 or 304.
AB  - The leukocyte NADPH oxidase is an enzyme in phagocytes and B lymphocytes that
      when activated catalyzes the production of O-2 from oxygen and NADPH. During
      oxidase activation, serine residues in the C-terminal quarter of the oxidase
      component p47(PHOX) become extensively phosphorylated, the protein acquiring as
      many as 9 phosphate residues. In a study of 11 p47(PHOX) mutants, each containing
      an alanine instead of a serine at a single potential phosphorylation site, we
      found that all but S379A corrected the defect in O-2 production in Epstein-Barr
      virus (EBV)-transformed p47(PHOX)-deficient B cells (Faust, L. P., El Benna, J.,
      Babior, B. M., and Chanock, S. J. (1995) J. Clin. Invest. 96, 1499-1505). In
      particular, O-2 production was restored to these cells by the mutants S303A and
      S304A. Therefore, apart from serine 379, whose state of phosphorylation in the
      activated oxidase is unclear, no single potential phosphorylation site appeared
      to be essential for oxidase activation. We now report that the double mutant
      p47(PHOX) S303A/S304A was almost completely inactive when expressed in EBV
      transformed p47(PHOX)-deficient B cells, even though it was expressed in normal
      amounts in the transfected cells and was able to translocate to the plasma
      membrane when the cells were stimulated. In contrast, the double mutant p47(PHOX)
      S303E/S304E was able to support high levels of O-2 production by EBV-transformed
      p47(PHOX)-deficient B cells. The surprising discovery that the double mutant
      S303K/S304K was also able to support considerable O-2 production suggests either
      that the effect of phosphorylation is related to the increase in hydrophilicity
      around serines 303 and 304 or that activation involves the formation of a metal
      bridge between the phosphorylated serines and another region of the protein.

PMID- 9545284
TI  - Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of
      cytokine gene expression in human thymocytes.
AB  - Proliferating human medullary thymocytes can exhibit characteristic T helper cell
      type 1 cytokine responses exemplified by the immediate early expression of
      interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and lymphotoxin
      beta. Here we report that cAMP-mediated attenuation of the transcription of T
      helper-1-specific cytokine genes in human medullary thymocytes correlates with
      the induction of the cAMP-mediated transcriptional repressor ICER (inducible cAMP
      early repressor). We show that ICER binds specifically to several NFAT/AP-1
      (nuclear factor of activated T cells/activating protein-1) composite DNA sites
      essential for the activation of the interleukin (IL)-2 promoter as well as to a
      homologous DNA motif present in the proximal segment of the interferon-gamma
      promoter. In the presence of the minimal NFAT DNA-binding domain, which is
      sufficient for both DNA binding and AP-1 complex formation, ICER and NFAT form
      NFAT/ICER ternary complexes on several NFAT/AP-1 DNA composite sites previously
      identified as essential for the expression of the immunoregulatory cytokines such
      as IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and tumor
      necrosis factor-alpha. In extracts prepared from human medullary thymocytes
      treated with forskolin and ionomycin, these composite sites bind endogenously
      expressed ICER either singly or in complexes. Moreover, in Jurkat cells,
      ectopically expressed ICER represses transcription from NFAT-mediated, phorbol
      ester/ionophore-activated IL-2, granulocyte-macrophage colony-stimulating factor,
      and tumor necrosis factor-alpha promoters. We present evidence that ICER
      interactions with NFAT/AP-1 composite DNA sites correlate with its ability to
      repress transcription. These findings provide further insight into the mechanisms
      involved in cAMP-mediated transcriptional attenuation of cytokine expression.

PMID- 9545285
TI  - Inhibition of CCAAT/enhancer-binding protein alpha and beta translation by
      upstream open reading frames.
AB  - CCAAT/enhancer-binding protein (C/EBP) alpha is a bZIP transcription factor whose
      expression is restricted to specific cell types. Analysis of C/EBPalpha mRNA and
      protein levels in various mammalian cells indicates that expression of this gene
      is controlled both transcriptionally and post-transcriptionally. We report here
      that C/EBPalpha translation is repressed in several cell lines by an
      evolutionarily conserved upstream open reading frame (uORF), which acts in cis to
      inhibit C/EBPalpha translation. Mutations that disrupt the uORF completely
      abolished translational repression of C/EBPalpha. The related c/ebpbeta gene also
      contains an uORF that suppresses translation. The length of the spacer sequence
      between the uORF terminator and the ORF initiator codon (7 bases in all
      c/ebpalpha genes and 4 bases in c/ebpbeta homologs) is precisely conserved. The
      effects of insertions, deletions, and base substitutions in the C/EBPalpha spacer
      showed that both the length and nucleotide sequence of the spacer are important
      for efficient translational repression. Our data indicate that the uORFs regulate
      translation of full-length C/EBPalpha and C/EBPbeta and do not play a role in
      generating truncated forms of these proteins, as has been suggested by start site
      multiplicity models.

PMID- 9545286
TI  - Characterization of the p125 subunit of human DNA polymerase delta and its
      deletion mutants. Interaction with cyclin-dependent kinase-cyclins.
AB  - The catalytic subunit of human DNA polymerase (pol) delta was overexpressed in an
      active, soluble form by the use of a baculovirus system in insect cells. The
      recombinant enzyme was separated from endogenous DNA polymerases by
      phosphocellulose, Mono Q-Sepharose, and single-stranded DNA-cellulose
      chromatography. Recombinant DNA pol delta was also purified by immunoaffinity
      chromatography. The enzymatic properties of the purified catalytic subunit were
      characterized. The enzyme was active and possessed both DNA polymerase and
      associated 3' to 5' exonuclease activities. NH2-terminal deletion mutants
      retained polymerase activity, whereas the core and COOH-terminal deletion mutants
      were devoid of any measurable activities. Coinfection of Sf9 cells with
      recombinant baculovirus vectors for pol delta and cyclin-dependent kinase (cdk)
      cyclins followed by metabolic labeling with 32Pi showed that the recombinant
      catalytic subunit of pol delta could be hyperphosphorylated by G1 phase-specific
      cdk-cyclins. When cdk2 was coexpressed with pol delta in Sf9 cells, pol delta was
      found to coimmunoprecipitate with antibodies against cdk2. Experiments with
      deletion mutants of pol delta showed that the NH2-terminal region was essential
      for this interaction. Coimmunoprecipitation and Western blot experiments in Molt
      4 cells confirmed the interaction in vivo. Preliminary experiments showed that
      phosphorylation of the catalytic subunit of pol delta by cdk2-cyclins had little
      or no effect on the specific activity of the enzyme.

PMID- 9545287
TI  - Dynamic cross-linking by alpha-actinin determines the mechanical properties of
      actin filament networks.
AB  - We used smooth muscle alpha-actinin to evaluate the contribution of cross-linker
      dynamics to the mechanical properties of actin filament networks. Recombinant
      actin-binding domain (residues 2-269) binds actin filaments with a Kd of 1 microM
      at 25 degrees C, 20 times stronger than actin-binding domain produced by
      thermolysin digestion of native alpha-actinin (residues 25-257). Between 8 and 25
      degrees C the rate constants for recombinant actin-binding domain to bind to (0.8
      2.7 microM-1 s-1) and dissociate from (0.2-2.4 s-1) actin filaments depend on
      temperature. At 8 degrees C actin filaments cross-linked with alpha-actinin are
      stiff and nearly solid, whereas at 25 degrees C the mechanical properties
      approach those of actin filaments alone. In these experiments, high actin
      concentrations kept most of the alpha-actinin bound to actin and temperature
      varied a single parameter, cross-linker dynamics, because the mechanical
      properties of pure actin filaments (a viscoelastic gel) or biotinylated actin
      filaments cross-linked irreversibly by avidin (a stiff viscoelastic solid) depend
      little on temperature. These results show that the rate of exchange of dynamic
      cross-links between actin filaments is an important determinant of the mechanical
      properties of the networks.

PMID- 9545288
TI  - The guanylyltransferase domain of mammalian mRNA capping enzyme binds to the
      phosphorylated carboxyl-terminal domain of RNA polymerase II.
AB  - We have conducted a biochemical and genetic analysis of mouse mRNA capping enzyme
      (Mce1), a bifunctional 597-amino acid protein with RNA triphosphatase and RNA
      guanylyltransferase activities. The principal conclusions are as follows: (i) the
      mammalian capping enzyme consists of autonomous and nonoverlapping functional
      domains; (ii) the guanylyltransferase domain Mce1(211-597) is catalytically
      active in vitro and functional in vivo in yeast in lieu of the endogenous
      guanylyltransferase Ceg1; (iii) the guanylyltransferase domain per se binds to
      the phosphorylated RNA polymerase II carboxyl-terminal domain (CTD), whereas the
      triphosphatase domain, Mce1(1-210), does not bind to the CTD; and (iv) a mutation
      of the active site cysteine of the mouse triphosphatase elicits a strong growth
      suppressive phenotype in yeast, conceivably by sequestering pre-mRNA ends in a
      nonproductive complex or by blocking access of the endogenous yeast
      triphosphatase to RNA polymerase II. These findings contribute to an emerging
      model of mRNA biogenesis wherein RNA processing enzymes are targeted to nascent
      polymerase II transcripts through contacts with the CTD. The phosphorylation
      dependent interaction between guanylyltransferase and the CTD is conserved from
      yeast to mammals.

PMID- 9545289
TI  - Identifying Lys359 as a critical residue for the ATP-dependent reactions of
      Drosophila DNA topoisomerase II.
AB  - Substituting Lys359 with either Gln or Glu in the highly conserved QTK-loop in
      the DNA gyrase B protein homologous domain of Drosophila topoisomerase II
      inactivates its catalytic activities. Although strand passage and DNA-dependent
      ATPase activities are affected in these mutant proteins, their DNA cleavage
      activity is comparable with the wild-type enzyme and can be stimulated to the
      same level by topoisomerase-targeting anticancer drugs. The sequence specificity
      in the DNA cleavage reaction remains unaltered for the mutant proteins. We have
      used both glass fiber filter binding assay and CsCl density gradient
      ultracentrifugation to monitor the formation of a salt-stable, protein-clamp
      complex. Both Gln and Glu mutant proteins can form a clamp complex in the
      presence of 5'-adenylyl-beta,gamma-imidodiphosphate, albeit with a lower
      efficiency than the wild-type enzyme. However, the mutant proteins can form a
      stable complex either in the presence of ATP or in the absence of any cofactors.
      These results are in an interesting contrast with the wild-type enzyme, which
      cannot form a stable complex under similar conditions. Our data suggest that
      Lys359 is critical for the catalytic activity of topoisomerase II and may have an
      important function in the ATP signaling process.

PMID- 9545290
TI  - Rationale for reclassification of a distinctive subdivision of mammalian class Mu
      glutathione S-transferases that are primarily expressed in testis.
AB  - A rat testicular Mu-class glutathione S-transferase (GST) resolved by reversed
      phase high performance liquid chromatography cross-reacted with peptide sequence
      specific antisera raised against the human hGSTM3 subunit. Electrospray
      ionization mass spectrometry indicated that this rat GST subunit (designated
      rGSTM5 in this report) has a significantly greater molecular mass (26,541 Da)
      than the other rat GST subunits. The mouse homologue (mGSTM5 subunit) was also
      identified and characterized by high performance liquid chromatography and
      electrospray ionization mass spectrometry. Sequence analysis of rGSTM5 peptide
      fragments and the sequence deduced from a cDNA clone showed that the protein is
      highly homologous to the hGSTM3 and murine mGSTM5 subunits. All three GSTs of
      this subclass have N- and C-terminal extensions with C-terminal cysteine
      residues, but the two penultimate amino acids near the C terminus are divergent
      in the three species. The proteins of this class Mu subfamily have similar
      catalytic specificities and mechanisms, are all cysteine rich, are found mainly
      in testis, and share characteristics that distinguish them from other GSTs.
      Moreover, the rGSTM5 subunit isolated from rat testis was not found in
      heterodimeric combination with other common Mu-class GST subunits. As the rGSTM5,
      mGSTM5, and hGSTM3 subunits are structurally more closely related to each other
      than they are to other Mu GSTs, it is proposed that they be considered a
      functionally distinct and separate subfamily within class Mu. The identification
      of this unique mammalian GST subclass could advance strategies for interspecies
      comparisons of GSTs and provides a rodent model for studies on functions and
      regulatory mechanisms for human GSTs.

PMID- 9545291
TI  - Re-evaluating the role of His-143 in the mechanism of type I dehydroquinase from
      Escherichia coli using two-dimensional 1H,13C NMR.
AB  - Type I dehydroquinase from the shikimate pathway of Escherichia coli dehydrates
      dehydroquinate to dehydroshikimate. pH/log Vmax profiles of the enzyme indicate
      the presence of a single ionizing group with a pKa of 6.2. Chemical modification
      experiments with diethyl pyrocarbonate have identified the conserved residue His
      143 as essential for catalysis in this enzyme and the pKa for this modification
      is also 6.2, implying that this is the single ionizing residue in dehydroquinase
      that may be acting as a general base in the catalytic mechanism. Subsequent
      mutagenesis of this residue (Leech, A. P., James, R., Coggins, J. R., and
      Kleanthous, C. (1995) J. Biol. Chem. 270, 25827-25836) further suggested that His
      143 may be involved in Schiff base formation/breakdown as well as being the
      proton abstracting general base. The importance of this residue was confirmed by
      recent x-ray crystallographic data showing His-143 to be at the center of a
      hydrogen-bonded triad, flanked by the essential Schiff base forming residue Lys
      170 and Glu-86. In the present study, we have used mutagenesis and 1H and 13C NMR
      to assign the resonance of His-143 and probe its ionization state to define more
      precisely its role in the mechanism of type I dehydroquinase. Following isotopic
      enrichment of wild-type and H143A dehydroquinase enzymes with [2-13C]histidine,
      the resonance for His-143 was assigned by comparing their 1H,13C heteronuclear
      single quantum correlation NMR spectra. pH titrations revealed that whether in
      the liganded or unliganded state, His-143 does not ionize over the pH range 6-9.5
      and so cannot possess a pKa of 6.2. The NMR data are consistent with this residue
      remaining unprotonated at pH values optimal for the activity of this enzyme (pH >
      7). The role of His-143 is re-evaluated in light of these and the recent
      structural data, and an alternative candidate for the pKa of 6.2 is discussed.

PMID- 9545292
TI  - Mutation of the sialyltransferase S-sialylmotif alters the kinetics of the donor
      and acceptor substrates.
AB  - Protein sequence analysis of the cloned sialyltransferase gene family has
      revealed the presence of two conserved protein motifs in the middle of the
      lumenal catalytic domain, termed L-sialylmotif and S-sialylmotif. In our previous
      study (Datta, A. K., and Paulson, J. C. (1995) J. Biol. Chem. 270, 1497-1500) the
      larger L-sialylmotif of ST6Gal I was analyzed by site-directed mutagenesis, which
      provided evidence that it participates in the binding of the CMP-NeuAc, a common
      donor substrate for all the sialyltransferases. However, none of the mutants
      tested in this motif had any significant effect on their binding affinities
      toward the acceptor substrate asialo alpha1-acid glycoprotein. In this study, we
      have investigated the role of the S-sialylmotif of the same enzyme ST6Gal I. In
      total, nine mutants have been constructed by changing the conserved amino acids
      of this motif to mostly alanine by site-directed mutagenesis. Kinetic analysis
      for the mutants which retained sialyltransferase activity showed that the
      mutations in the S-sialylmotif caused a change of Km values for both the donor
      and the acceptor substrates. Our results indicated that this motif participates
      in the binding of both the substrates. A sequence homology search also supported
      this finding, which showed that the downstream amino acid sequence of the S
      sialylmotif is conserved for each subgroup of this enzyme family, indicating its
      association with the acceptor substrate.

PMID- 9545293
TI  - Identification of the N-linked oligosaccharide sites in chick corneal lumican and
      keratocan that receive keratan sulfate.
AB  - Corneal proteoglycans have chondroitin/dermatan and keratan sulfate (KS) chains
      and belong to the leucine-rich proteoglycan gene family. Corneal KS is N-linked
      to Asn of an NX(S/T) site through a complex oligosaccharide linkage region. Only
      some sites receive KS, whereas others remain in a high mannose form. To determine
      whether the attachment of KS was biased toward specific sites, we isolated
      trypsin-digested KS-containing fragments of chick corneal proteoglycans and
      sequenced the peptides. Results showed that all of the peptides sequenced aligned
      to the deduced amino acid sequence of either chick lumican or chick keratocan at
      the first, third, and fourth potential N-linked sites. Sites 1 and 4 in lumican
      and keratocan are in a homologous location. By analogy with the structure of
      ribonuclease inhibitor (a Leu-rich repeat containing protein), the KS chains
      would extend outward on the outer face of a horseshoe-like structure. The amino
      acid sequences surrounding the potential N-linked sites were also compared. Sites
      receiving KS tend to have a higher occurrence of aromatic residues, in particular
      Phe, located within 3 amino acids of NX(S/T). These conserved Phe residues may
      have a role in the conversion of high mannose N-linked oligosaccharides to
      polylactosamine and/or keratan sulfate.

PMID- 9545294
TI  - A novel -2Fe-2S- ferredoxin from Pseudomonas putida mt2 promotes the reductive
      reactivation of catechol 2,3-dioxygenase.
AB  - Catechol 2,3-dioxygenase (XylE) is a component of the TOL plasmid-encoded pathway
      for the degradation of toluene and xylenes and catalyzes the dioxygenolytic
      cleavage of the aromatic ring. Purified XylE is oxygen-sensitive and unstable in
      vitro, particularly in the presence of substituted catechol substrates, but it is
      stabilized in vivo by another protein, XylT, encoded by the xylT gene located
      just upstream of xylE. In this study, we have purified to homogeneity the XylT
      product from a recombinant Escherichia coli strain containing a hyperexpressible
      xylT gene and characterized it as a novel [2Fe-2S] ferredoxin. It is the first
      example of a soluble ferredoxin with a net positive charge at neutral pH. The EPR
      signal of the iron sulfur cluster has rhombic symmetry as is the case for plant
      type ferredoxins, but the XylT absorbance spectrum resembles more closely that of
      adrenodoxin. The midpoint redox potential was determined to be -373 +/- 6 mV, at
      pH 8. 5. XylT was unusually unstable for a [2Fe-2S] ferredoxin, with half-lives
      of 69 min at 25 degrees C in air and 70 min at 37 degrees C in argon. With
      photochemically reduced 5-deazaflavin for the controlled generation of reductant,
      it was demonstrated that XylT mediates the rapid reactivation of purified
      inactive catechol 2,3-dioxygenase in vitro. Inactivation of XylE by 4
      methylcatechol resulted in oxidation of the active site iron to a high spin
      ferric state that was detectable by EPR. Spectroscopic evidence presented here
      demonstrates that XylT reactivates XylE through reduction of the iron atom in the
      active site of the enzyme. It is the first instance of a ferredoxin-mediated
      reactivation of an enzyme. The level of expression of XylT in Pseudomonas putida
      mt2 cells is low and the calculated XylT/XylE molar ratio is consistent with the
      proposal that XylE reactivation involves catalytic nonstoichiometric amounts of
      XylT.

PMID- 9545295
TI  - Expression of a plastidic ATP/ADP transporter gene in Escherichia coli leads to a
      functional adenine nucleotide transport system in the bacterial cytoplasmic
      membrane.
AB  - Recently, a second type of eucaryotic adenine nucleotide transporter located in
      the inner envelope membrane of higher plants has been identified at the molecular
      level (Neuhaus, H. E., Thom, E., Mohlmann, T., Steup, M., and Kampfenkel, K.
      (1997) Plant J. 11, 73-82). Here we have analyzed the biochemical properties of
      this ATP/ADP transporter from Arabidopsis thaliana (AATP1, At). This analysis was
      carried out by expressing a cDNA encoding this carrier as a histidine-tagged
      chimeric protein heterologously in Escherichia coli. Isopropyl-1-thio-beta-D
      galactopyranoside (IPTG)-induced E. coli cells were able to import radioactively
      labeled [alpha-32P]ATP. Uninduced E. coli cells did not import [alpha-32P]ATP.
      Further control experiments revealed that IPTG induction did not promote import
      of other phosphorylated or unphosphorylated metabolites into the bacterial cell
      indicating the specificity of [alpha-32P]ATP transport. [alpha-32P]ATP uptake
      into induced E. coli cells was linear with time for several minutes allowing for
      determination of kinetic constants. The apparent Km for ATP was 17 microM which
      is close to values reported on the authentic protein in isolated plastids. ADP
      was a strong competitive inhibitor of -alpha-32P-ATP uptake (Ki ADP 3.6 microM).
      Other metabolites like AMP, ADP glucose, UTP, UDP, NAD, and NADP did not
      influence [alpha-32P]ATP uptake. IPTG-induced E. coli cells preloaded with [alpha
      32P]ATP exported radioactively labeled adenylates after exogenous addition of
      unlabeled ATP or ADP indicating a counter exchange mechanism of transport. The
      biochemical properties of the heterologously expressed AATP1 gene product
      demonstrated that the protein is functionally integrated in the cytoplasmic
      membrane of E. coli. This is the first report of the functional expression of a
      plant membrane protein in E. coli leading to new transport properties across the
      cytoplasmic membrane. The functional integration of a plant membrane protein in
      the cytoplasmic membrane of E. coli offers new possibilities for future studies
      of the structural and mechanistic properties of this transporter. Since IPTG
      induction allowed synthesis of a 67-kDa protein in E. coli, which was
      subsequently specifically enriched by metal-chelate chromatography, this
      procaryotic heterologous expression system might provide a suitable system for
      overproduction of membrane proteins of eucaryotic origin in the near future.

PMID- 9545296
TI  - Protein disulfide isomerase acts as a molecular chaperone during the assembly of
      procollagen.
AB  - Protein-disulfide isomerase (PDI) has been shown to be a multifunctional enzyme
      catalyzing the formation of disulfide bonds, as well as being a component of the
      enzymes prolyl 4-hydroxylase (P4-H) and microsomal triglyceride transfer protein.
      It has also been proposed to function as a molecular chaperone during the
      refolding of denatured proteins in vitro. To investigate the role of this
      multifunctional protein within a cellular context, we have established a semi
      permeabilized cell system that reconstitutes the synthesis, folding,
      modification, and assembly of procollagen as they would occur in the cell. We
      demonstrate here that P4-H associates transiently with the triple helical domain
      during the assembly of procollagen. The release of P4-H from the triple helical
      domain coincides with assembly into a thermally stable triple helix. However, if
      triple helix formation is prevented, P4-H remains associated, suggesting a role
      for this enzyme in preventing aggregation of this domain. We also show that PDI
      associates independently with the C-propeptide of monomeric procollagen chains
      prior to trimer formation, indicating a role for this protein in coordinating the
      assembly of heterotrimeric molecules. This demonstrates that PDI has multiple
      functions in the folding of the same protein, that is, as a catalyst for
      disulfide bond formation, as a subunit of P4-H during proline hydroxylation, and
      independently as a molecular chaperone during chain assembly.

PMID- 9545297
TI  - Purification and characterization of the Sgs1 DNA helicase activity of
      Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae Sgs1 protein is a member of a family of DNA
      helicases that include the Escherichia coli RecQ protein and the products of
      human Bloom's syndrome and Werner's syndrome genes. To study the enzymatic
      characteristics of the protein, a recombinant Sgs1 fragment (amino acids 400-1268
      of the 1447-amino acid full-length protein) was overexpressed in yeast and
      purified to near homogeneity. The purified protein exhibits an ATPase activity in
      the presence of single- or double-stranded DNA. In the presence of ATP or dATP,
      unwinding of duplex DNA or a DNA-RNA heteroduplex by the recombinant Sgs1
      fragment was readily observed. Similar to the E. coli RecQ helicase, displacement
      of the DNA strand occurs in the 3' to 5' direction with respect to the single
      stranded DNA flanking the duplex. The efficiency of unwinding was found to
      correlate inversely with the length of the duplex region and was enhanced by the
      presence of E. coli single-stranded DNA-binding protein. In addition, the
      recombinant Sgs1 fragment was found to bind more tightly to a forked DNA
      substrate than to either single- or double-stranded DNA.

PMID- 9545298
TI  - Up-regulation of glucosylceramide synthase expression and activity during human
      keratinocyte differentiation.
AB  - During keratinocyte differentiation, the glycolipid, glucosylceramide (GlcCer),
      is thought to be synthesized, stored in intracellular lamellar granules and
      eventually extruded into the intercellular space where GlcCer is hydrolyzed to
      ceramide, a major component of the epidermal permeability barrier. Previous
      studies showed that GlcCer synthase (GCS) activity increases during keratinocyte
      differentiation; however, the mechanism by which GCS activity is regulated was
      not established. In the present study, we prepared anti-peptide antibodies and
      amplified cDNA probes based on the cDNA sequence for human GCS (Ichikawa, S.,
      Sakiyama, H., Suzuki, G., Hidari, K. I.-P. J., and Hirabayashi, Y. (1996) Proc.
      Natl. Acad. Sci. U. S. A. 93, 4638-4643) in order to study GCS expression during
      keratinocyte differentiation. Confluent human keratinocytes in culture were
      induced to terminally differentiate by elevation of Ca+2 in the medium without
      exogenous hormones or growth factors. GlcCer synthesis assayed in situ using a
      fluorescent ceramide analog increased approximately 5-fold during keratinocyte
      differentiation, peaking at day 6. Fluorescence microscopy studies of living
      keratinocytes showed that fluorescent ceramide and/or its metabolites accumulated
      in the Golgi in undifferentiated cells but targeted to unique vesicular
      structures that may be derived from the trans-Golgi region. Expression of both
      GCS mRNA, a approximately 3. 8-kilobase transcript on Northern blots, and GCS
      protein, a approximately 38-kDa polypeptide detected by Western blotting,
      increased dramatically (approximately 5-fold) during differentiation, reaching a
      maximum at about day 8. These results suggest that GCS is up-regulated at the
      transcriptional level during keratinocyte differentiation and provide the first
      direct evidence for GCS up-regulation in any cell type.

PMID- 9545299
TI  - Crystal structure of human RhoA in a dominantly active form complexed with a GTP
      analogue.
AB  - The 2.4-A resolution crystal structure of a dominantly active form of the small
      guanosine triphosphatase (GTPase) RhoA, RhoAV14, complexed with the
      nonhydrolyzable GTP analogue, guanosine 5'-3-O-(thio)triphosphate (GTPgammaS),
      reveals a fold similar to RhoA-GDP, which has been recently reported (Wei, Y.,
      Zhang, Y., Derewenda, U., Liu, X., Minor, W., Nakamoto, R. K., Somlyo, A. V.,
      Somlyo, A. P., and Derewenda, Z. S. (1997) Nat. Struct. Biol. 4, 699-703), but
      shows large conformational differences localized in switch I and switch II. These
      changes produce hydrophobic patches on the molecular surface of switch I, which
      has been suggested to be involved in its effector binding. Compared with H-Ras
      and other GTPases bound to GTP or GTP analogues, the significant conformational
      differences are located in regions involving switches I and II and part of the
      antiparallel beta-sheet between switches I and II. Key residues that produce
      these conformational differences were identified. In addition to these
      differences, RhoA contains four insertion or deletion sites with an extra helical
      subdomain that seems to be characteristic of members of the Rho family, including
      Rac1, but with several variations in details. These sites also display large
      displacements from those of H-Ras. The ADP-ribosylation residue, Asn41, by C3
      like exoenzymes stacks on the indole ring of Trp58 with a hydrogen bond to the
      main chain of Glu40. The recognition of the guanosine moiety of GTPgammaS by the
      GTPase contains water-mediated hydrogen bonds, which seem to be common in the Rho
      family. These structural differences provide an insight into specific interaction
      sites with the effectors, as well as with modulators such as guanine nucleotide
      exchange factor (GEF) and guanine nucleotide dissociation inhibitor (GDI).

PMID- 9545300
TI  - A novel lectin from Sarcophaga. Its purification, characterization, and cDNA
      cloning.
AB  - A novel C-type lectin that agglutinates rabbit red cells was purified from NIH
      Sape-4 cells derived from the flesh fly (Sarcophaga peregrina), and its cDNA was
      isolated. This lectin, named granulocytin, appeared to be a trimer of a 20-kDa
      subunit consisting of 151 amino acid residues. The gene for granulocytin was
      activated in third instar larvae, and its expression was enhanced when the larval
      body wall was injured. In third instar larvae, granulocytin was found to be
      synthesized by hemocytes and secreted into the hemolymph. The molecular mass and
      gene expression patterns of granulocytin were very similar to those of Drosophila
      lectin that we reported previously (Haq, S., Kubo, T., Kurata, S., Kobayashi, A.,
      and Natori, S. (1996) J. Biol. Chem. 271, 20213-20218). However, these two
      lectins showed amino acid identities of 20% at most, and no significant hapten
      sugar for granulocytin was identified.

PMID- 9545301
TI  - The 55-kDa tumor necrosis factor receptor induces clustering of mitochondria
      through its membrane-proximal region.
AB  - The cytokine tumor necrosis factor (TNF) activates diverse signaling molecules
      resulting in gene expression, differentiation, and/or cell death. Here we report
      a novel feature induced by TNF, namely translocation of mitochondria from a
      dispersed distribution to a perinuclear cluster. Mitochondrial translocation
      correlated with sensitivity to the cell death-inducing activity of TNF and was
      mediated by the 55-kDa TNF receptor (TNF-R55), but not by Fas, indicating that
      the signaling pathway requires a TNF-R55-specific but death domain-independent
      signal. Indeed, using L929 cells that express mutant TNF-R55, we showed that the
      membrane-proximal region of TNF-R55 was essential for signaling to mitochondrial
      translocation. In the absence of translocation, the cell death response was
      markedly delayed, pointing to a cooperative effect on cell death. Translocation
      of mitochondria, although dependent on the microtubules, was not imposed by the
      latter and was equally induced by TNF-independent immunoinhibition of the motor
      protein kinesin. Additionally, immunoinhibition with antibody directed against
      the tail domain of kinesin synergized with TNF-induced cell death. Based on this
      functional mimicry, we propose that a TNF-R55 membrane-proximal region-dependent
      signal impedes mitochondria-associated kinesin, resulting in cooperation with the
      TNF-R55 death domain-induced cytotoxic response and causing the observed
      clustering of mitochondria.

PMID- 9545302
TI  - Oxidized low density lipoprotein induces apoptosis in cultured human umbilical
      vein endothelial cells by common and unique mechanisms.
AB  - Oxidized low density lipoprotein (oxLDL) induces apoptosis in vascular cells. To
      elucidate the mechanisms involved in this apoptosis, we studied the apoptosis
      inducing activity in lipid fractions of oxLDL and the roles of two common
      mechanisms, ceramide generation and the activation of caspases, in apoptosis in
      human umbilical vein endothelial cells treated with oxLDL. We also studied the
      effects of antioxidants and cholesterol. oxLDL induced endothelial apoptosis in a
      time- and dose-dependent fashion. Apoptosis-inducing activity was recovered in
      the neutral lipid fraction of oxLDL. Various oxysterols in this fraction induced
      endothelial apoptosis. Neither the phospholipid fraction nor its component
      lysophosphatidylcholine induced apoptosis. oxLDL induced ceramide accumulation
      temporarily at 15 min in a dose-dependent fashion. Two inhibitors of acid
      sphinogomyelinase inhibited both the increase in ceramide and the apoptosis
      induced by oxLDL. Furthermore, a membrane-permeable ceramide (C2-ceramide)
      induced endothelial apoptosis. These findings demonstrated that ceramide
      generation by acid sphingomyelinase is indispensable for the endothelial
      apoptosis induced by oxLDL. Inhibitors of both caspase-1 and caspase-3 inhibited
      the apoptosis, suggesting that oxLDL induced apoptosis by activating these
      cysteine proteases. The antioxidants butylated hydroxytoluene and superoxide
      dismutase but not catalase inhibited the apoptosis induced by oxLDL or 25
      hydroxycholesterol. This suggests not only that superoxide plays an important
      role but also that a critical interaction between oxLDL and the cell takes place
      on the outer surface of the membrane, because superoxide dismutase is not
      membrane-permeable. Exogenous cholesterol also inhibited the apoptosis. Our study
      demonstrated that neutral lipids in oxLDL induce endothelial apoptosis by
      activating membrane sphingomyelinase in a superoxide-dependent manner, as well as
      by activating caspases.

PMID- 9545303
TI  - Site-directed mutagenesis of essential residues involved in the mechanism of
      bacterial glycosylasparaginase.
AB  - Flavobacterium glycosylasparaginase was cloned in an Escherichia coli expression
      system. Site-directed mutagenesis was performed at residues suggested to be
      important in the catalytic mechanism based on the crystal structure of the human
      enzyme and other biochemical studies. In vitro autoproteolysis allowed the mutant
      enzymes to be activated, including those that were slow to self-cleave. Based on
      the activity of the mutant enzymes, six catalytically essential amino acids were
      identified: Trp-11, Asp-66, Thr-152, Thr-170, Arg-180, and Asp-183. Kinetic
      analysis of each mutant further defined the function of these residues in
      substrate specificity and reaction rate. Mutagenesis of the N-terminal
      nucleophile residue Thr-152 confirmed the key function of its side-chain hydroxyl
      group. Partial activities of mutants T152S/C were in agreement with the general
      mechanism of N-terminal nucleophile (Ntn)-amidohydrolases. The side-chain
      hydroxyl of Thr-170 contributes to the reaction rate based on studies of mutants
      T170S/C/A. Residues Asp-183 and Arg-180 were found to H-bond, respectively, with
      the charged alpha-amino and alpha-carboxyl group of the substrate (Asn-GlcNAc).
      Mutants R180Q/L and D183E/N had greatly decreased substrate affinity and reduced
      reaction rates. Kinetic studies also showed that Trp-11 is involved in regulation
      of the enzyme reaction rate, contradictory to a previous suggestion that this
      residue is involved in substrate binding. Asp-66 is a new residue found to be
      important in enzyme activity. The overall active site structure involving these
      catalytic residues resembles the glutaminase domain of glucosamine 6-phosphate
      synthase, another member of the Ntn-amidohydrolase family of enzymes.

PMID- 9545304
TI  - Characterization and functional analysis of the cis-autoproteolysis active center
      of glycosylasparaginase.
AB  - Glycosylasparaginase is an N-terminal nucleophile hydrolase and is activated by
      intramolecular autoproteolytic processing. This cis-autoproteolysis possesses
      unique kinetics characterized by a reversible N-O acyl rearrangement step in the
      processing. Arg-180 and Asp-183, involved in binding of the substrate in the
      mature enzyme, are also involved in binding of free amino acids in the partially
      formed substrate pocket on certain mutant precursors. This binding site is
      sequestered in the wild-type precursor. Binding of free amino acids on mutant
      precursors can either inhibit or accelerate their processing, depending on the
      individual mutants and amino acids. The polypeptide sequence at the processing
      site, which is highly conserved, adopts a special conformation. Asp-151 is
      essential for maintaining this conformation, possibly by anchoring its side chain
      into the partially formed substrate pocket through interaction with Arg-180. The
      reactive nucleophile Thr-152 is activated not only by deprotonation by His-150
      but also by interaction with Thr-170, suggesting a His-Thr-Thr active triad for
      the autoproteolysis.

PMID- 9545305
TI  - Activation of phosphatidylinositol 3-kinase through glycoprotein 130 induces
      protein kinase B and p70 S6 kinase phosphorylation in cardiac myocytes.
AB  - Phosphatidylinositol (PI) 3-kinase is known to be activated by cytokine
      stimulation through different types of receptors to transduce intracellular
      responses. We have previously reported that leukemia inhibitory factor (LIF)
      induces the activation of Janus kinase signal transducer and activator of
      transcription (JAK-STAT) and mitogen-activated protein (MAP) kinase pathways
      through glycoprotein (gp) 130 in cardiac myocytes. However, whether PI 3-kinase
      is involved in regulation of gp130 signaling and the activation mechanisms by
      which it associates with other tyrosine-phosphorylated proteins remain unknown.
      We found that LIF induced the activation of PI 3-kinase in cardiac myocytes.
      Moreover, JAK1 binds to PI 3-kinase, and LIF stimulation increases the PI 3
      kinase activity in JAK1 immunoprecipitates. Activation of MAP kinase and protein
      kinase B by LIF was attenuated by wortmannin. LIF-induced p70 S6 kinase
      activation, protein synthesis, and c-fos mRNA expression were inhibited by
      wortmannin and rapamycin. Both inhibitors failed to appreciably affect the
      phosphorylation of STAT3. In conclusion, PI 3-kinase is activated with LIF in
      cardiac myocytes, and JAK1 is found to associate with this enzyme. PI 3-kinase
      provides a crucial link between gp130, MAP kinase, protein kinase B, and p70 S6
      kinase in cardiac myocytes.

PMID- 9545306
TI  - Cleavage of BP180, a 180-kDa bullous pemphigoid antigen, yields a 120-kDa
      collagenous extracellular polypeptide.
AB  - The hemidesmosome (HD) is a cell-to-substrate adhesion apparatus found in
      stratified and complex epithelia. One of the putative cell-matrix adhesion
      molecules present in the HD is the 180-kDa bullous pemphigoid antigen (BP180),
      also termed type XVII collagen. In our previous study, using a monoclonal
      antibody (mAb) 1337, we have detected a 120-kDa collagenase-sensitive polypeptide
      in the HD fraction (Uematsu, J. and Owaribe, K. (1993) Cell Struct. Funct. 18,
      588 (abstr.)). The present study was undertaken to assess the relation of the 120
      kDa polypeptide to this BP180. Immunofluorescence microscopy of bovine skin
      revealed the basement membrane zone of skin to be stained clearly with mAb 1337,
      whereas the lateral surfaces of basal cells, which were decorated by typical
      antibodies against BP180, were not. The antibody did not detect HDs in cultured
      cells but rather in the culture medium. These results indicate a localization of
      mAb 1337 antigen distinct from BP180. However, the same polypeptide was also
      recognized by monoclonal antibodies to the extracellular but not the cytoplasmic
      part of BP180, and found to react with a polyclonal antibody against the non
      collagenous 16A domain of BP180. Therefore, the polypeptide was identified as an
      extracellular fragment of BP180. mAb 1337 immunoprecipitated the 120-kDa fragment
      from the medium, but not the 180-kDa molecule of BP180 extracted from cultured
      cells, indicating that the antibody specifically recognizes the fragment. The mAb
      1337 apparently recognizes a unique epitope that is exposed or formed by the
      cleavage. Hence, the staining pattern observed for bovine skin demonstrated the
      presence of the 120-kDa extracellular fragment. Rotary shadow electron microscopy
      of affinity-purified 120-kDa fragments demonstrated that they have the unique
      molecular shape consisting of a central rod and a flexible tail, without the
      globular head that is present in the BP180 molecule. From these results, we
      conclude that mAb 1337 shows unique epitope specificity, recognizing only the 120
      kDa extracellular fragment of BP180, which is constitutively cleaved on the cell
      surface as a 120-kDa fragment both in in vivo and in vitro.

PMID- 9545307
TI  - A peptide sequence of heparin/heparan sulfate (HP/HS)-interacting protein
      supports selective, high affinity binding of HP/HS and cell attachment.
AB  - We previously have identified a novel cell surface heparan sulfate/heparin
      (HS/HP)-interacting protein (HIP) found in human uterine epithelia and a variety
      of other human epithelial and endothelial cells and cell lines (Liu, S., Smith,
      S. E., Julian, J., Rohde, L. H., Karin, N. J., and Carson, D. D. (1996) J. Biol.
      Chem. 271, 11817-11823; Rohde, L. H., Julian, J., Babaknia, A., and Carson, D. D.
      (1996) J. Biol. Chem. 271, 11824-11830). The amino acid sequence predicted for
      HIP revealed a potential HS/HP-binding motif. In the present studies, a synthetic
      peptide corresponding to this putative HS/HP-binding motif, HIP peptide, was
      synthesized and examined with regard to its HS/HP binding and cell attachment
      promoting activity. Results using solid phase binding assays demonstrate that HIP
      peptide binds HS/HP with high selectivity and has high affinity for bulk HP (50%
      saturation congruent with 300 nM) and even higher affinity for a subset of
      polysaccharides found in commercial [3H]HP (half-saturation congruent with 10
      nM). Moreover, HIP peptide binds subsets of cell and extracellular matrix
      associated HS and dermatan sulfate expressed by RL95 cells, a human uterine
      adenocarcinoma cell line. HIP peptide also binds a similar fraction of HS as well
      as dermatan sulfate expressed by JAR cells, a human choriocarcinoma cell line. In
      contrast to binding of cell- or extracellular matrix-associated HS, HIP peptide
      does not bind secreted or released forms of HS or DS from either RL95 or JAR
      cells to a significant extent. HS species that bind to HIP peptide are generally
      larger, have a higher negative charge density, and have a larger proportion of di
      and trisulfated disaccharide units than HS species that do not bind to HIP
      peptide, demonstrating structural differences among these polysaccharides. This
      same peptide supports HS-dependent JAR cell attachment. Collectively, these data
      demonstrate that a linear peptide sequence found within HIP can account, at least
      in part, for the HS/HP binding and cell adhesion promoting activities of this
      protein.

PMID- 9545308
TI  - Increased expression of acetylcholinesterase T and R transcripts during
      hematopoietic differentiation is accompanied by parallel elevations in the levels
      of their respective molecular forms.
AB  - Differentiation of hematopoietic cells is known to be accompanied by profound
      changes in acetylcholinesterase (AChE) enzyme activity, yet the basic mechanisms
      underlying this developmental regulation remain unknown. We initiated a series of
      experiments to examine the molecular mechanisms involved in regulating AChE
      expression during hematopoiesis. Differentiation of murine erythroleukemia (MEL)
      cells using dimethyl sulfoxide resulted in a 5- and 10-fold increase in
      intracellular and secreted AChE enzyme activity, respectively. Interestingly,
      these increases resulted from a preferential induction of the globular molecular
      form G1 and a slight increase in G4 instead of an increase in the levels of the
      G2 membrane-bound form, a molecular form expressed in mature erythrocytes.
      Concomitantly, expression of the two predominant AChE transcripts (R and T, for
      read-through and tail, respectively) in MEL cells was induced to a similar extent
      with differentiation. Nuclear run-on assays performed with nuclei isolated from
      induced versus uninduced MEL cells revealed that in contrast to the large
      increases seen in the transcription of the beta-globin gene, the transcriptional
      activity of the AChE gene remained largely unaffected after differentiation.
      Determination of the half-lives of the R and T transcripts demonstrated that they
      both exhibited an increase in stability in induced MEL cells. Taken together,
      results from these studies indicate that post-transcriptional regulatory
      mechanisms account for the increased expression of AChE in differentiated
      hematopoietic cells.

PMID- 9545310
TI  - Visualization of a slow, ATP-induced structural transition in the bacterial
      molecular chaperone DnaK.
AB  - Recent reports have shown that the binding of ATP to a 70-kDa molecular chaperone
      induces a rapid global conformational transition from a "high affinity" state to
      a "low affinity" state, where these states are defined by tight and weak binding
      to (poly)peptides, respectively. To complete the activity cycle, a chaperone
      molecule must ultimately return to the high affinity state. In this report, this
      return to the high affinity state was studied using a chemical cross-linking
      assay in conjunction with SDS-polyacrylamide gel electrophoresis. The basis for
      this assay is that in the absence of nucleotide or in the presence of ADP,
      conditions that stabilize the high affinity state, cross-linking of the
      Escherichia coli molecular chaperone DnaK yielded two monomeric forms, with
      apparent molecular masses of 70 kDa (77%) and 90 kDa (23%), whereas cross-linking
      yielded only the 70-kDa monomeric form in the presence of ATP. This ATP-dependent
      difference in cross-linking was used to follow the kinetics of the low affinity
      to high affinity transition under single turnover conditions. The rate of this
      transition (kobs = 3.4 (+/-0.6) x 10(-4) s-1 at 25 degrees C) is almost identical
      to the reported rate of ATP hydrolysis (khy = 2.7 (+/-0.7) x 10(-4) s-1 at 22
      degrees C). These results are consistent with a two-step sequential reaction
      where rate-limiting ATP hydrolysis precedes the conformational change. Models for
      the formation of two cross-linked DnaK monomers in the absence of ATP are
      discussed.

PMID- 9545309
TI  - Ubiquitination is required for the retro-translocation of a short-lived luminal
      endoplasmic reticulum glycoprotein to the cytosol for degradation by the
      proteasome.
AB  - In the endoplasmic reticulum (ER), an efficient "quality control system" operates
      to ensure that mutated and incorrectly folded proteins are selectively degraded.
      We are studying ER-associated degradation using a truncated variant of the rough
      ER-specific type I transmembrane glycoprotein, ribophorin I. The truncated
      polypeptide (RI332) consists of only the 332 amino-terminal amino acids of the
      protein corresponding to most of its luminal domain and, in contrast to the long
      lived endogenous ribophorin I, is rapidly degraded. Here we show that the
      ubiquitin-proteasome pathway is involved in the destruction of the truncated
      ribophorin I. Thus, when RI332 that itself appears to be a substrate for
      ubiquitination was expressed in a mutant hamster cell line harboring a
      temperature-sensitive mutation in the ubiquitin-activating enzyme E1 affecting
      ubiquitin-dependent proteolysis, the protein is dramatically stabilized at the
      restrictive temperature. Moreover, inhibitors of proteasome function effectively
      block the degradation of RI332. Cell fractionation experiments indicate that
      RI332 accumulates in the cytosol when degradation is prevented by proteasome
      inhibitors but remains associated with the lumen of the ER under ubiquitination
      deficient conditions, suggesting that the release of the protein into the cytosol
      is ubiquitination-dependent. Accordingly, when ubiquitination is impaired, a
      considerable amount of RI332 binds to the ER chaperone calnexin and to the Sec61
      complex that could effect retro-translocation of the polypeptide to the cytosol.
      Before proteolysis of RI332, its N-linked oligosaccharide is cleaved in two
      distinct steps, the first of which might occur when the protein is still
      associated with the ER, as the trimmed glycoprotein intermediate efficiently
      interacts with calnexin and Sec61. From our data we conclude that the steps that
      lead a newly synthesized luminal ER glycoprotein to degradation by the proteasome
      are tightly coupled and that especially ubiquitination plays a crucial role in
      the retro-translocation of the substrate protein for proteolysis to the cytosol.

PMID- 9545311
TI  - Promoter structures and differential responses to viral and nonviral inducers of
      chicken type I interferon genes.
AB  - Two serologically distinct type I interferons (IFNs), designated ChIFN1 and
      ChIFN2, are known in the chicken. ChIFN1 is encoded by a family of 10 or more
      genes, whereas ChIFN2 is encoded by a single gene. We show here that ChIFN1 and
      ChIFN2 transcripts are both strongly induced by Newcastle disease virus in
      primary chicken macrophages. By contrast, oral administration of the
      imidazoquinoline S-28463, which selectively induces IFN-alpha in mammals, led to
      a rapid accumulation of ChIFN1 (but not ChIFN2) transcripts in adult chicken
      spleen and thymus. The 5'-upstream region of the ChIFN2 gene contains a NF-kappaB
      consensus motif flanked by a sequence element that could serve as a binding site
      for transcription factor IRF-1, reminiscent of mammalian IFN-beta promoters, and
      it mediated powerful virus inducibility in a duck fibroblast cell line when
      cloned in front of a promoterless luciferase reporter gene. The 5'-upstream
      region of the cloned ChIFN1 gene contains two putative binding sites for IRF-1,
      but lacks NF-kappaB-binding sites, and it did not respond well to virus in
      transfected cells. Thus, the promoters of ChIFN1 and ChIFN2 genes not only
      exhibited differential responses to nonviral inducers in vivo, but also differed
      in structure and response to virus in transfected cells. These findings indicate
      that ChIFN2 represents the avian homolog of mammalian IFN-beta, whereas ChIFN1
      seems to correspond to mammalian IFN-alpha.

PMID- 9545312
TI  - Enhancement of serum-response factor-dependent transcription and DNA binding by
      the architectural transcription factor HMG-I(Y).
AB  - The mechanisms by which HMG-I proteins regulate cell growth are unknown, and
      their effects on gene expression have only been partially elucidated. We explored
      the potential interaction between HMG-I proteins and serum-response factor (SRF),
      a member of the MADS-box family of transcription factors. In cotransfection
      experiments, HMG-I(Y) potentiated SRF-dependent activation (by more than 5-fold)
      of two distinct SRF-responsive promoters, c-fos and the smooth muscle-specific
      gene SM22alpha. This effect was also observed with a heterologous promoter
      containing multiple copies of the CC(A/T)6GG (CArG) box. HMG-I proteins bound
      specifically to the CArG boxes of c-fos and SM22alpha in gel mobility shift
      analysis and enhanced binding of SRF to these CArG boxes. By chelating peptide
      immobilized metal affinity chromatography, we mapped the domain of HMG-I(Y) that
      interacts with SRF to amino acids 50-81, a region that does not bind specifically
      to DNA in electrophoretic mobility shift assays even though it includes the third
      AT-hook DNA-binding domain. Surprisingly, HMG-I(Y) mutants that failed to bind
      DNA still enhanced SRF binding to DNA and SRF-dependent transcription. In
      contrast, deletion of the HMG-I(Y) 50-81 domain that bound SRF prevented
      enhancement of transcription. To our knowledge, this is the first report of an
      HMG-I protein interacting with a MADS-box transcription factor. Our observations
      suggest that members of the HMG-I family play an important role in SRF-dependent
      transcription and that their effect is mediated primarily by a protein-protein
      interaction.

PMID- 9545313
TI  - Collapsin response mediator protein-2 is associated with neurofibrillary tangles
      in Alzheimer's disease.
AB  - Intraneuronal accumulation of paired helical filaments (PHF) is considered to be
      closely related to the neuronal loss observed in brains of patients affected with
      Alzheimer's disease. The central issue is whether PHF formation itself causes or
      accelerates the neuronal perikaryal and neuritic degeneration or whether they are
      simply the consequence of preceding degeneration. We sought to address the issue
      in part by characterizing the PHF-associated molecules and thus raised a number
      of monoclonal antibodies to neurofibrillary tangles. One monoclonal antibody,
      3F4, strongly reacted with neurofibrillary tangles and some plaque neurites but
      few neuropil threads. This monoclonal antibody labeled a 65-kDa protein, but not
      tau or ubiquitin, on a Western blot of human brain extract and immunoprecipitated
      the same protein. The peptides released from the purified 65-kDa protein had the
      same sequences as those of a newly identified protein, human collapsin response
      mediator protein-2. Incorporation into neurofibrillary tangles may deplete
      soluble, cytosolic human collapsin response mediator protein-2 and lead to
      abnormal neuritic and/or axonal outgrowth of the tangle-bearing neuron, thus
      accelerating the neuritic degeneration in Alzheimer's disease.

PMID- 9545314
TI  - Differential effects of transforming growth factor-beta on the expression of
      collagenase-1 and collagenase-3 in human fibroblasts.
AB  - Collagenase-3 (MMP-13) is a matrix metalloproteinase (MMP) originally identified
      in breast carcinomas which is also produced at significant levels during fetal
      ossification and in arthritic processes. In this work, we have found that
      transforming growth factor beta1 (TGF-beta1), a growth factor widely assumed to
      be inhibitory for MMPs, strongly induces collagenase-3 expression in human KMST
      fibroblasts. In contrast, this growth factor down-regulated the expression in
      these cells of collagenase-1 (MMP-1), an enzyme highly related to collagenase-3
      in terms of structure and enzymatic properties. The positive effect of TGF-beta1
      on collagenase-3 expression was dose- and time-dependent, but independent of the
      effects of this growth factor on cell proliferation rate. Analysis of the signal
      transduction mechanisms underlying the up-regulating effect of TGF-beta1 on
      collagenase-3 expression demonstrated that this growth factor acts through a
      signaling pathway involving protein kinase C and tyrosine kinase activities.
      Functional analysis of the collagenase-3 gene promoter region revealed that the
      inductive effect of TGF-beta1 is partially mediated by an AP-1 site. Comparative
      analysis with the promoter region of the collagenase-1 gene which contains an AP
      1 site at equivalent position, confirmed that TGF-beta1 did not have any effect
      on CAT activity levels of this promoter. Finally, by using electrophoretic
      mobility shift assays and antibody supershift analysis, we propose that c-Fos, c
      Jun, and JunD may play major roles in the collagenase-3 activation by TGF-beta1
      in human fibroblasts.

PMID- 9545315
TI  - Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard.
      Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase
      activating polypeptide and glucagon-like peptide 1 and evidence against the
      existence of mammalian homologues.
AB  - Helodermin and exendin-4, two peptides isolated from the salivary gland of the
      Gila monster, Heloderma suspectum, are approximately 50% homologous to vasoactive
      intestinal peptide (VIP) and glucagon-like peptide-1 (GLP-1), respectively, and
      interact with the mammalian receptors for VIP and GLP-1 with equal or higher
      affinity and efficacy. Immunohistochemical studies suggested the presence of
      helodermin-like peptides in mammals. To determine whether helodermin and exendin
      4 are present in mammals and their evolutionary relationship to VIP and GLP-1,
      their cDNAs were first cloned from Gila monster salivary gland. Northern blots
      and reverse transcription-polymerase chain reaction of multiple Gila monster
      tissues identified approximately 500-base pair transcripts only from salivary
      gland. Both helodermin and exendin-4 full-length cDNAs were approximately 500
      base pairs long, and they encoded precursor proteins containing the entire amino
      acid sequence of helodermin and exendin-4, as well as a 44- or 45-amino acid N
      terminal extension peptide, respectively, having approximately 60% homology. The
      size and structural organization of these cDNAs indicated that they were closely
      related to one another but markedly different from known cDNAs for the VIP/GLP-1
      peptide family previously identified in both lower and higher evolved species.
      Cloning of the Gila monster VIP/peptide histidine isoleucine, pituitary adenylate
      cyclase activating polypeptide, and glucagon/GLP-1 cDNAs and Southern blotting of
      Gila monster DNA demonstrate the coexistence of separate genes for these peptides
      and suggests, along with the restricted salivary gland expression, that
      helodermin and exendin-4 coevolved to serve a separate specialized function.
      Probing of a variety of rat and human tissues on Northern blots, human and rat
      Southern blots, and genomic and cDNA libraries with either helodermin- or exendin
      4-specific cDNAs failed to identify evidence for mammalian homologues. These data
      indicate that helodermin and exendin-4 are not the precursors to VIP and GLP-1
      and that they belong to a separate peptide family encoded by separate genes.
      Furthermore, the existence of as yet undiscovered mammalian homologues to
      helodermin and exendin-4 seems unlikely.

PMID- 9545316
TI  - An enzymatically active chimeric HIV-1 reverse transcriptase (RT) with the RNase
      H domain of murine leukemia virus RT exists as a monomer.
AB  - The existence of retroviral reverse transcriptases as monomers or dimers is
      rather intriguing. A classical example of the former is murine leukemia virus
      reverse transcriptase (MuLV RT), while human immunodeficiency virus type 1 (HIV
      1) RT represents the latter. A careful scrutiny of the amino acid sequence
      alignment of the two enzymes pinpoints the region tentatively responsible for
      this phenomenon. We report here the construction of a chimeric enzyme containing
      the first 425 amino acid residues from the N-terminal domain of HIV-1 RT and 200
      amino acid residues from the C-terminal domain of MuLV RT. The chimeric enzyme
      exists as a monomer with intact DNA polymerase and RNase-H functions.

PMID- 9545317
TI  - Analysis of the DNA-binding site for Xenopus glucocorticoid receptor accessory
      factor. Critical nucleotides for binding specificity in vitro and for
      amplification of steroid-induced fibrinogen gene transcription.
AB  - In addition to the glucocorticoid receptor, DNA-binding proteins called accessory
      factors play a role in hormone activation of many glucocorticoid-responsive
      genes. Hormonal regulation of the gamma-fibrinogen subunit gene from the frog
      Xenopus laevis requires a novel DNA sequence that binds a liver nuclear protein
      called Xenopus glucocorticoid receptor accessory factor (XGRAF). Here we
      demonstrate that the recognition site for XGRAF encompasses GAGTTAA at positions 
      175 to -169 relative to the start site of transcription. This sequence is not
      closely related to the binding sites for known transcription factors. The two
      guanosines make close contact with XGRAF, as shown by the methylation
      interference assay. Single-point mutagenesis of every nucleotide in the 9-base
      pair region from positions -177 to -169 showed an excellent correlation between
      ability to bind XGRAF in vitro and ability to amplify hormone-induced
      transcription from DNA transfected into Xenopus primary hepatocytes. Conversely,
      XGRAF had little or no effect on basal transcription of the gamma-fibrinogen
      gene. Maximal hormonal induction also requires three half-glucocorticoid response
      elements (half-GREs) homologous to the downstream half of the consensus GRE.
      Interestingly, the XGRAF-binding site is immediately adjacent to the most
      important half-GRE. This close proximity suggests a new mechanism for activation
      of a gene lacking a conventional full GRE.

PMID- 9545318
TI  - Kinesin is a candidate for cross-bridging microtubules and intermediate
      filaments. Selective binding of kinesin to detyrosinated tubulin and vimentin.
AB  - We showed previously that stable, detyrosinated (Glu) microtubules function to
      localize vimentin intermediate filaments in fibroblasts (Gurland, G., and
      Gundersen, G. G. (1995) J. Cell Biol. 131, 1275-1290). To identify candidate
      proteins that mediate the Glu microtubule-vimentin interaction, we incubated
      microtubules with microtubule-interacting proteins and saturating levels of
      antibodies to Glu or tyrosinated (Tyr) tubulin. Antibodies to Glu tubulin
      prevented the microtubule binding of kinesin obtained from fibroblast or brain
      extracts more effectively than antibodies to Tyr tubulin. Scatchard plot analysis
      showed that kinesin heads bound to Glu microtubules with an approximately 2.8
      fold higher affinity than to Tyr microtubules. Purified brain kinesin
      cosedimented with vimentin, but not with neurofilaments, indicating that kinesin
      specifically associates with vimentin without accessory molecules. Kinesin
      binding to vimentin was not sensitive to ATP, and kinesin heads failed to bind to
      vimentin. By SDS-polyacrylamide gel electrophoresis, a kinesin heavy chain of
      approximately 120 kDa and a light chain of approximately 64 kDa were detected in
      vimentin/kinesin pellets. The light chain reacted with a general kinesin light
      chain antibody, but not with two other antibodies that recognize the two known
      isoforms of kinesin light chain in brain, suggesting that the kinesin involved in
      binding to vimentin may be a specific one. These results demonstrate a kinesin
      based mechanism for the preferential interaction of vimentin with detyrosinated
      microtubules.

PMID- 9545319
TI  - Mechanisms involved in the acidosis enhancement of the isoproterenol-induced
      phosphorylation of phospholamban in the intact heart.
AB  - Previous experiments have shown that acidosis enhances isoproterenol-induced
      phospholamban (PHL) phosphorylation (Mundina-Weilenmann, C., Vittone, L.,
      Cingolani, H. E., Orchard, C. H. (1996) Am. J. Physiol. 270, C107-C114). In the
      present experiments, performed in isolated Langendorff perfused rat hearts,
      phosphorylation site-specific antibodies to PHL combined with the quantitative
      measurement of 32P incorporation into PHL were used as experimental tools to gain
      further insight into the mechanism involved in this effect. At all isoproterenol
      concentrations tested (3-300 nM), phosphorylation of Thr17 of PHL was
      significantly higher at pHo 6.80 than at pHo 7.40, without significant changes in
      Ser16 phosphorylation. This increase in Thr17 phosphorylation was associated with
      an enhancement of the isoproterenol-induced relaxant effect. In the absence of
      isoproterenol, the increase in [Ca]o at pHo 6.80 (but not at pHo 7.40) evoked an
      increase in PHL phosphorylation that was exclusively due to an increase in Thr17
      phosphorylation and that was also associated with a significant relaxant effect.
      This effect and the phosphorylation of Thr17 evoked by acidosis were both offset
      by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62. In the
      presence of isoproterenol, either the increase in [Ca]o or the addition of a 1
      microM concentration of the phosphatase inhibitor okadaic acid was able to mimic
      the increase in isoproterenol-induced Thr17 phosphorylation produced by acidosis.
      In contrast, these two interventions have opposite effects on phosphorylation of
      Ser16. Whereas the increase in [Ca]o significantly decreased phosphorylation of
      Ser16, the addition of okadaic acid significantly increased the phosphorylation
      of this residue. The results are consistent with the hypothesis that the increase
      in phospholamban phosphorylation produced by acidosis in the presence of
      isoproterenol is the consequence of two different mechanisms triggered by
      acidosis: an increase in [Ca2+]i and an inhibition of phosphatases.

PMID- 9545320
TI  - Identification of a novel type of alternatively spliced exon from the
      acetylcholinesterase gene of Bungarus fasciatus. Molecular forms of
      acetylcholinesterase in the snake liver and muscle.
AB  - The venom of the snake Bungarus fasciatus contains a hydrophilic, monomeric
      species of acetylcholinesterase (AChE), characterized by a C-terminal region that
      does not resemble the alternative T- or H-peptides. Here, we show that the snake
      contains a single gene for AChE, possessing a novel alternative exon (S) that
      encodes the C-terminal region of the venom enzyme, located downstream of the T
      exon. Alternative splicing generates S mRNA in the venom gland and S and T mRNAs
      in muscle and liver. We found no evidence for the presence of an H exon between
      the last common "catalytic" exon and the T exon, where H exons are located in
      Torpedo and in mammals. Moreover, COS cells that were transfected with AChE
      expression vectors containing the T exon with or without the preceding genomic
      region produced exclusively AChET subunits. In the snake tissues, we could not
      detect any glycophosphatidylinositol-anchored AChE form that would have derived
      from H subunits. In the liver, the cholinesterase activity comprises both AChE
      and butyrylcholinesterase components; butyrylcholinesterase corresponds
      essentially to nonamphiphilic tetramers and AChE to nonamphiphilic monomers
      (G1na). In muscle, AChE is largely predominant: it consists of globular forms
      (G1a and G4a) and trace amounts of asymmetric forms (A8 and A12), which derive
      from AChET subunits. Thus, the Bungarus AChE gene possesses alternatively spliced
      T and S exons but no H exon; the absence of an H exon may be a common feature of
      AChE genes in reptiles and birds.

PMID- 9545321
TI  - Combinatorial action of HNF3 and Sp family transcription factors in the
      activation of the rabbit uteroglobin/CC10 promoter.
AB  - It has been reported that respiratory epithelium-specific transcription is
      mediated by thyroid transcription factor 1 and members of the HNF3/forkhead
      family of transcription factors. Here, we show that the uteroglobin/Clara cell 10
      kDa promoters from rabbit and man are regulated by HNF3alpha and HNF3beta but not
      by HFH-4 and TTF-1. We have identified two HNF3-responsive elements in the rabbit
      uteroglobin/CC10 promoter located around 95 and 130 base pairs upstream of the
      transcriptional start site. Both elements contribute to promoter activity in H441
      cells expressing uteroglobin/CC10 and HNF3alpha. Gene transfer experiments into
      Drosophila Schneider cells that lack many mammalian transcription factor homologs
      revealed that HNF3alpha and HNF3beta on their own cannot activate the
      uteroglobin/CC10 promoter. However, HNF3alpha and HNF3beta strongly enhanced Sp1
      mediated promoter activation. Synergistic activation by HNF3alpha and Sp1 was
      absolutely dependent on the integrity of two Sp1 sites located at around -65 and 
      230. We show further that multiple activation domains of Sp1 are required for
      cooperativity with HNF3alpha. These studies demonstrate that transcription from
      the rabbit uteroglobin/CC10 promoter in lung epithelium is controlled by the
      combinatorial action of the cell-specific factor HNF3alpha and the ubiquitous
      factor Sp1.

PMID- 9545322
TI  - The PEL1 gene (renamed PGS1) encodes the phosphatidylglycero-phosphate synthase
      of Saccharomyces cerevisiae.
AB  - Phosphatidylglycerophosphate (PG-P) synthase catalyzes the synthesis of PG-P from
      CDP-diacylglycerol and sn-glycerol 3-phosphate and functions as the committed and
      rate-limiting step in the biosynthesis of cardiolipin (CL). In eukaryotic cells,
      CL is found predominantly in the inner mitochondrial membrane and is generally
      thought to be an essential component of many mitochondrial functions. We have
      determined that the PEL1 gene (now renamed PGS1), previously proposed to encode a
      second phosphatidylserine synthase of yeast (Janitor, M., Jarosch, E., Schweyen,
      R. J., and Subik, J. (1995) Yeast 13, 1223-1231), in fact encodes a PG-P synthase
      of Saccharomyces cerevisiae. Overexpression of the PGS1 gene product under the
      inducible GAL1 promoter resulted in a 14-fold increase in in vitro PG-P synthase
      activity. Disruption of the PGS1 gene in a haploid strain of yeast did not lead
      to a loss of viability but did result in a dependence on a fermentable carbon
      source for growth, a temperature sensitivity for growth, and a petite lethal
      phenotype. The pgs1 null mutant exhibited no detectable in vitro PG-P synthase
      activity and no detectable CL or phosphatidylglycerol (PG); significant CL
      synthase activity was still present. The growth arrest phenotype and lack of PG-P
      synthase activity of a pgsA null allele of Escherichia coli was corrected by an N
      terminal truncated derivative of the yeast PG-P synthase. These results
      unequivocally demonstrate that the PGS1 gene encodes the major PG-P synthase of
      yeast and that neither PG nor CL are absolutely essential for cell viability but
      may be important for normal mitochondrial function.

PMID- 9545323
TI  - ATP-dependent assembly of a ternary complex consisting of a DNA mismatch and the
      yeast MSH2-MSH6 and MLH1-PMS1 protein complexes.
AB  - MSH2 and MSH6 proteins exist as a stable complex, as do the MLH1 and PMS1
      proteins. To study the mismatch binding properties of the MSH2-MSH6 complex and
      to examine its functional interaction with the MLH1-PMS1 complex, these protein
      complexes were purified to near homogeneity from overproducing yeast strains. As
      has been reported previously, the purified MSH2-MSH6 complex binds DNA substrates
      containing a G/T mismatch and insertion/deletion mismatches, but the binding
      affinity for the latter decreases as the size of the extrahelical loop increases.
      Addition of ATP or the nonhydrolyzable ATPgammaS reduces binding of the MSH2-MSH6
      complex to the DNA substrates markedly. Here, we show that MSH2-MSH6 forms a
      ternary complex with MLH1-PMS1 on a mismatch containing DNA substrate. The
      formation of this ternary complex requires ATP, which can be substituted by
      ATPgammaS, suggesting that ATP binding alone is sufficient for ternary complex
      formation. Thus, it appears that ATP binding by the MSH2-MSH6 complex induces a
      conformation that is conducive for the interaction with MLH1-PMS1 complex,
      leading to the formation of the ternary complex.

PMID- 9545324
TI  - Lysosomal enzyme trafficking between phagosomes, endosomes, and lysosomes in J774
      macrophages. Enrichment of cathepsin H in early endosomes.
AB  - In this study we take advantage of recently developed methods using J774
      macrophages to prepare enriched fractions of early endosomes, late endosomes,
      dense lysosomes, as well as phagosomes of different ages enclosing 1-micron latex
      beads to investigate the steady state distribution and trafficking of lysosomal
      enzyme activity between these organelles. At steady state these cells appear to
      possess four different cellular structures, in addition to phagolysosomes, where
      acid hydrolases were concentrated. The first site of hydrolase concentration was
      the early endosomes, which contained the bulk of the cellular cathepsin H. This
      enzyme was acquired by phagosomes significantly faster than the other hydrolases
      tested. The second distinct site of lysosomal enzyme concentration was the late
      endosomes which contain the bulk of cathepsin S. The third and fourth large pools
      of hydrolases were found in two functionally distinct types of dense lysosomes,
      only one of which was found to be secreted in the presence of chloroquine or
      bafilomycin. Among this secreted pool was soluble furin, generally considered
      only as a membrane-bound trans-Golgi network resident protein. Thus, the
      organelles usually referred to as "lysosomes" in fact encompass a growing family
      of highly dynamic but functionally distinct endocytic organelles.

PMID- 9545325
TI  - Metastasis-associated Mts1 (S100A4) protein modulates protein kinase C
      phosphorylation of the heavy chain of nonmuscle myosin.
AB  - Mts1 protein (S100A4 according to a new classification) has been implicated in
      the formation of the metastatic phenotype via regulation of cell motility and
      invasiveness. Previously we have demonstrated that Mts1 protein interacted with
      the heavy chain of nonmuscle myosin in a calcium-dependent manner. To elucidate
      the role of the Mts1-myosin interaction, we mapped the Mts1-binding region on the
      myosin heavy chain molecule. We prepared proteolytically digested platelet myosin
      and a series of overlapped myosin heavy chain protein fragments and used them in
      a blot overlay with Mts1 protein. Here we report that the Mts1-binding site is
      located within a 29-amino acid region, at the C-terminal end of the myosin heavy
      chain (between 1909-1937 amino acids). Two-dimensional phosphopeptide analysis
      showed that Mts1 protein inhibits protein kinase C phosphorylation of the
      platelet myosin heavy chain at Ser-1917. We hypothesize that Mts1 protein
      regulates cytoskeletal dynamics of the metastatic cells through modulation of the
      myosin phosphorylation by protein kinase C in calcium-dependent fashion.

PMID- 9545326
TI  - ERcalcistorin/protein-disulfide isomerase acts as a calcium storage protein in
      the endoplasmic reticulum of a living cell. Comparison with calreticulin and
      calsequestrin.
AB  - ERcalcistorin/protein-disulfide isomerase (ECaSt/PDI), a high capacity low
      affinity Ca2+-binding protein in the endoplasmic reticulum of sea urchin eggs
      (Lebeche, D., and Kaminer, B. (1992) Biochem. J. 287, 741-747), shares 55%
      sequence identity with mammalian PDI and has PDI activity (Lucero, H., Lebeche,
      D., and Kaminer, B. (1994) J. Biol. Chem. 269, 23112-23119). We report on
      ECaSt/PDI functioning as a Ca2+ storage protein in the endoplasmic reticulum (ER)
      of a living cell and compare it with calsequestrin and calreticulin, high
      capacity low affinity Ca2+-binding proteins in the sarcoplasmic reticulum and ER,
      respectively. Stably transfected Chinese hamster ovary cell clones expressed
      these proteins, which were localized in the ER of the cell. Microsomes from cells
      expressing ECaSt/PDI, calreticulin, and calsequestrin accumulated 17.2 +/- 0.27,
      20.0 +/- 0.82, and 38.0 +/- 0.28 nmol of Ca2+/mg of protein, respectively;
      control microsomes accumulated from 2.6 +/- 0.17 to 2.9 +/- 0.14 nmol of Ca2+/mg
      of protein. The initial rate of Ca2+ uptake was similar in microsomes from
      transfected and control cells. Microsomes containing an ECaSt/PDI mutant in which
      45% of the acidic residue pairs in the C terminus were truncated had a reduced
      Ca2+ storage capacity. This supports our previous hypothesis that the degree of
      low affinity Ca2+ binding is dependent on the number of pairs of carboxyl groups
      in the molecule. The maximal Ca2+ accumulation by microsomes containing the
      expressed ECaSt/PDI, C-terminally truncated ECaSt/PDI, calreticulin, or
      calsequestrin correlates approximately with the Ca2+ binding capacity of the
      respective proteins.

PMID- 9545327
TI  - Regulation of interleukin-13 receptor constituents on mature human B lymphocytes.
AB  - Human B cells stimulated through both their immunoglobulin and CD40 receptors up
      regulate 745 +/- 51 interleukin (IL)-13 ligand binding sites with an affinity of
      0.91 +/- 0.08 nM within 24 h. IL-13 binds primarily to the IL-13Ralpha1 with
      subsequent sequestration of the IL-4Ralpha into the complex. IL-13Ralpha1 may
      also be found in those receptors capable of binding IL-4. gamma chain (gammac)
      participates in receptors capable of binding IL-4 but is not found in association
      with bound IL-13. Dimeric receptors composed of the IL-4Ralpha complexed with
      either the IL-13Ralpha1 or gammac occur simultaneously within defined B cell
      populations. mRNAs for all receptor constituents are increased subsequent to
      immunoglobulin stimulation alone, while maximal expression of IL-13Ralpha1 is
      more dependent upon co-stimulation of immunoglobulin and CD40 receptors. mRNA
      levels for IL-13Ralpha1 vary over a wider range subsequent to surface stimulation
      than other receptor components. Although gammac is not bound to IL-13 in B cells
      under the conditions evaluated, it may influence IL-13 binding by competing with
      IL-13Ralpha1 for association/sequestration with the IL-4Ralpha chain. IL
      13Ralpha2 does not participate in the IL-13 receptor that is up-regulated upon
      activation of quiescent tonsillar B lymphocytes, although mRNA for the protein
      may be found in the centroblastic fraction of tonsillar cells.

PMID- 9545328
TI  - Reduction in abortive transcription from the lambdaPR promoter by mutations in
      region 3 of the sigma70 subunit of Escherichia coli RNA polymerase.
AB  - Transcription initiation by Escherichia coli RNA polymerase at most promoters is
      associated with a reiterative synthesis and release of short abortive RNA
      products. We have investigated the mechanism of abortive RNA synthesis by using
      holoenzymes containing mutant sigma70 subunits with changes in region 3 (S506F
      and P504L), which reduce the ratio of abortive to full-length products. Binary
      complexes formed by these mutant enzymes at a modified lambdaPR promoter
      contained a smaller fraction of open complexes than for normal polymerase,
      suggesting an involvement of region 3 in melting duplex DNA or in maintenance of
      the open complex. The half-lives of the majority of binary complexes formed by
      the mutant enzymes were less than 1 min, in contrast to 30 min for the wild-type
      complexes. The time courses of transcription and pulse-labeling assays showed
      that moribund complexes, which generate only abortive products (Kubori, T., and
      Shimamoto, N. (1996) J. Mol. Biol. 256, 449-457), were formed by the mutant
      enzymes. However, they accumulated to a lesser extent than for the wild-type
      enzyme, due both to faster dissociation and conversion into inactive complexes.
      This is the main cause of the low degree of abortive transcription displayed by
      the mutant enzymes on this promoter.

PMID- 9545329
TI  - Agonist-induced sequestration, recycling, and resensitization of platelet
      activating factor receptor. Role of cytoplasmic tail phosphorylation in each
      process.
AB  - Agonist-induced sequestration, recycling, and resensitization of platelet
      activating factor (PAF) receptor were characterized in transfected Chinese
      hamster ovary cells. Exposure of the cells to PAF led to rapid sequestration of
      the receptors into the intracellular compartment and desensitization of the
      response to PAF. The sequestration was inhibited by pretreatments that perturbed
      the clathrin-mediated pathway. Subsequent removal of PAF by washing with receptor
      antagonists led to rapid recycling of the sequestered receptors to the cell
      surface accompanied by resensitization to PAF. To evaluate the potential role of
      phosphorylation in the receptor cytoplasmic tail during these processes, mutant
      receptors in which the tails were truncated or substituted, so as to lack
      serine/threonine residues, were created. PAF phosphorylated the wild-type
      receptor rapidly and strongly, but the mutants did not. The maximal extent of
      sequestration of each mutant was lower than that of the wild-type, and one of the
      substituted mutants showed no sequestration. Furthermore, the sequestration
      defective mutant showed evidence of desensitization after agonist stimulation but
      not resensitization after agonist removal. Thus, agonist-induced phosphorylation
      of the cytoplasmic tail facilitates but is not essential for receptor
      sequestration, and sequestration/recycling appears important in receptor
      resensitization.

PMID- 9545330
TI  - Subcellular localization of prostaglandin endoperoxide H synthases-1 and -2 by
      immunoelectron microscopy.
AB  - Prostaglandin endoperoxide H synthases-1 and -2 (PGHS-1 and -2) are the major
      targets of nonsteroidal anti-inflammatory drugs like aspirin and ibuprofen. These
      enzymes catalyze the committed step in the formation of prostanoids from
      arachidonic acid. Although PGHS-1 and -2 are similar biochemically, a number of
      studies suggest that PGHS-1 and PGHS-2 function independently to form prostanoids
      that subserve different cellular functions. We have hypothesized that these
      isozymes may reside, at least in part, in different subcellular compartments and
      that their compartmentation may affect their access to arachidonic acid and serve
      to separate the functions of the enzymes. To obtain high resolution data on the
      subcellular locations of PGHS-1 and -2, we employed immunoelectron microscopy
      with multiple antibodies specific to each isozyme. Both PGHS-1 and -2 were found
      on the lumenal surfaces of the endoplasmic reticulum (ER) and nuclear envelope of
      human monocytes, murine NIH 3T3 cells, and human umbilical vein endothelial
      cells. Within the nuclear envelope, PGHS-1 and -2 were present on both the inner
      and outer nuclear membranes and in similar proportions. Western blotting data
      showed a similar distribution of PGHS-1 and -2 in subcellular fractions, and
      product analysis using isozyme-specific inhibitors suggested that both enzymes
      generate the same products in NIH 3T3 cells. Thus, we are unable to attribute the
      independent functioning of PGHS-1 and PGHS-2 to differences in their subcellular
      locations. Instead, the independent operation of these isozymes may be
      attributable to subtle kinetic differences (e.g. negative allosteric regulation
      of PGHS-1 at low concentrations of arachidonate (500-1000 nM)). A further
      conclusion of importance from a cell biological perspective is that membrane
      proteins such as PGHS-1 and -2, which are located on the lumenal surface of the
      ER, are able to diffuse freely among the ER and the inner and outer membranes of
      the nuclear envelope.

PMID- 9545331
TI  - Direct photoaffinity labeling of cysteine-295 of alpha-tubulin by guanosine 5'
      triphosphate bound in the nonexchangeable site.
AB  - The alphabeta-tubulin heterodimer has two high affinity guanosine 5'-triphosphate
      binding sites, so that purified tubulin usually contains two molecules of bound
      guanosine nucleotide. Half this nucleotide is freely exchangeable with exogenous
      guanine nucleotide, and its binding site has been readily localized to the beta
      subunit. The remaining nonexchangeable guanosine 5'-triphosphate can only be
      released from tubulin by denaturing the protein. We replaced the exchangeable
      site nucleotide of tubulin with 2'-deoxyguanosine 5'-diphosphate, exposed the
      resulting tubulin to ultraviolet light, degraded the protein, and isolated ribose
      containing peptide derived from the nonexchangeable site. A large cyanogen
      bromide peptide was recovered, and its further degradation with endoproteinase
      Glu-C established that cysteine-295 of alpha-tubulin was the major reactive amino
      acid cross-linked to guanosine by ultraviolet irradiation.

PMID- 9545332
TI  - A role for the insulin-interleukin (IL)-4 receptor motif of the IL-4 receptor
      alpha-chain in regulating activation of the insulin receptor substrate 2 and
      signal transducer and activator of transcription 6 pathways. Analysis by
      mutagenesis.
AB  - The interleukin (IL)-4 receptor alpha-chain (IL-4Ralpha) contains a sequence
      motif (488PLVIAGNPAYRSFSD) termed the insulin IL-4 receptor motif (I4R motif).
      Mutation of the central Tyr497 to Phe blocks the tyrosine phosphorylation of the
      insulin receptor substrate 1 (IRS1) and diminishes proliferation in response to
      IL-4. Recent data suggest that the I4R motif encodes binding sites for several
      protein tyrosine binding (PTB) domain-containing proteins such as IRS1 and Shc
      and potentially for the Src homology 2 domain of signal transducer and activator
      of transcription 6 (STAT6). To analyze the function of the I4R motif in
      regulating IL-4 signaling, we changed conserved residues upstream and downstream
      of the central Tyr to Ala in the human IL-4Ralpha. We analyzed the ability of
      these constructs to signal the tyrosine phosphorylation of IRS2 and STAT6, the
      induction of DNA binding activity, and CD23 induction in response to human IL-4
      (huIL-4) in transfected M12.4.1 cells. Mutagenesis of residues downstream of
      Tyr497, such as Arg498 or Phe500, to Ala had no effect on any of these responses,
      suggesting that the I4R motif may not be important for functional Src homology 2
      domain interactions. However, mutagenesis of Pro488 to Ala (P488A) greatly
      diminished the tyrosine phosphorylation of IRS2 and abolished tyrosine
      phosphorylation of STAT6, induction of DNA binding activity, and CD23 induction
      in response to huIL-4. By contrast, a P488G mutant signaled these responses to
      huIL-4. Mutagenesis of hydrophobic amino acids previously shown to contact the
      PTB domain of IRS1, Leu489 or Ile491, to Ala had only minimal effects on
      responses to huIL-4. However, changing both Leu498 and Ile491 to Ala greatly
      diminished the tyrosine phosphorylation of IRS2 and abolished STAT6 activation.
      Taken together, these results indicate the important role of the I4R motif in
      regulating IRS docking and suggest that I4R docking to a PTB domain-containing
      protein regulates activation of the STAT6 pathway.

PMID- 9545333
TI  - Cell growth inhibition by a novel vitamin K is associated with induction of
      protein tyrosine phosphorylation.
AB  - We have shown that a synthetic vitamin K analog, 2-(2-mercaptoethanol)-3-methyl
      1,4-naphthoquinone or compound 5 (Cpd 5), potently inhibits cell growth and
      suggested that the analog exerts its effects mainly via sulfhydryl arylation
      rather than redox cycling. Since protein-tyrosine phosphatases (PTPases), which
      have pivotal roles in many cellular functions, have a critical cysteine in their
      active site, we have proposed PTPases as likely targets for Cpd 5. To test this
      hypothesis, we examined the effects of Cpd 5 on protein tyrosine phosphorylation
      of cellular proteins and on the activity of PTPases. We found that Cpd 5 rapidly
      induced protein tyrosine phosphorylation in a human hepatocellular carcinoma cell
      line (Hep3B) at growth inhibitory doses, and the effect was blocked by thiols but
      not by non-thiol antioxidants or tyrosine kinase inhibitors. Cpd 5 inhibited
      PTPase activity, which was also significantly antagonized by reduced glutathione.
      Furthermore, the well studied PTPase inhibitor orthovanadate also induced protein
      tyrosine phosphorylation and growth inhibition in Hep3B cells. These results
      suggest that inhibition of cellular PTPases by sulfhydryl arylation and
      subsequent perturbation of protein tyrosine phosphorylation may be involved in
      the mechanisms of Cpd 5-induced cell growth inhibition.

PMID- 9545335
TI  - RhoB is stabilized by transforming growth factor beta and antagonizes
      transcriptional activation.
AB  - Transforming growth factor beta (TGF-beta) is the prototype for an evolutionarily
      conserved superfamily of secreted factors implicated in diverse biological
      phenomena. The pleiotropic responses to TGF-beta are initiated by a heteromeric
      receptor complex that binds and phosphorylates downstream effectors. Among these,
      the Smads have been extensively studied. However, less attention has been
      directed toward alternative downstream effectors and their participation in TGF
      beta signal transduction. We show that TGF-beta promotes accumulation of the
      labile monomeric GTPase RhoB by antagonizing its normal proteolytic destruction,
      presumably via the 26 S proteasome. RhoB accumulates in its isoprenylated form.
      Transient overexpression of wild type RhoB but not its dominant negative mutant
      RhoB-N19 antagonizes TGF-beta-mediated transcriptional activation. These results
      suggest a novel mechanism of regulation by TGF-beta and implicate RhoB as a
      negative regulator of TGF-beta signal transduction.

PMID- 9545334
TI  - Palindrome with spacer of one nucleotide is characteristic of the cis-acting
      unfolded protein response element in Saccharomyces cerevisiae.
AB  - When unfolded proteins are accumulated in the endoplasmic reticulum (ER), an
      intracellular signaling pathway termed the unfolded protein response (UPR) is
      activated to induce transcription of ER-localized molecular chaperones and
      folding enzymes in the nucleus. In Saccharomyces cerevisiae, at least six lumenal
      proteins including essential Kar2p and Pdi1p are known to be regulated by the
      UPR. We and others recently demonstrated that the basic-leucine zipper protein
      Hac1p/Ern4p functions as a trans-acting factor responsible for the UPR. Hac1p
      binds directly to the cis-acting unfolded protein response element (UPRE)
      responsible for Kar2p induction. Moreover, we showed that the KAR2 UPRE contains
      an E box-like palindrome separated by one nucleotide (CAGCGTG) that is essential
      for its function. We report here that the promoter regions of each of five target
      proteins (Kar2p, Pdi1p, Eug1p, Fkb2p, and Lhs1p) contain a single UPRE sequence
      that is necessary and sufficient for induction and that binds specifically to
      Hac1p in vitro. All of the five functional UPRE sequences identified contain a
      palindromic sequence that has, in four cases, a spacer of one C nucleotide. This
      unique characteristic of UPRE explains why only a specific set of proteins are
      induced in the UPR to cope with ER stress.

PMID- 9545336
TI  - The proton motive force, acting on acidic residues, promotes translocation of
      amino-terminal domains of membrane proteins when the hydrophobicity of the
      translocation signal is low.
AB  - We have shown previously that the first transmembrane segment of leader peptidase
      can function to translocate the polar amino-terminal Pf3 domain across the
      membrane into the periplasm independently of the proton motive force (pmf) (Lee,
      J. I., Kuhn, A., and Dalbey, R. E. (1992) J. Biol. Chem. 267, 938-943). We now
      show that when the first transmembrane segment lacks a strong hydrophobic
      character, the pmf is required for translocation. In addition, we find that the
      amino-terminal acidic residue proximal to the transmembrane domain plays a
      critical role in pmf-dependent amino-terminal translocation. Moreover, the pmf is
      required to hold the amino-terminal domain in the periplasm to prevent it from
      slipping such that the amino terminus is no longer exposed to the periplasm. In
      all cases, translocation occurs under conditions in which the function of the Sec
      machinery is impaired. These studies show that the low hydrophobicity of the
      first apolar domain (the translocation signal) can be compensated for by a
      negative charge in the amino-terminal region, upon which the pmf acts.

PMID- 9545337
TI  - Glycosaminoglycan binding properties of annexin IV, V, and VI.
AB  - We have previously demonstrated that annexin IV, one of the calcium/phospholipid
      binding annexin family proteins, binds to glycosaminoglycans (GAGs) in a calcium
      dependent manner (Kojima, K., Yamamoto, K., Irimura, T., Osawa, T., Ogawa, H.,
      and Matsumoto, I. (1996) J. Biol. Chem. 271, 7679-7685). In this study, we
      investigated the GAG binding specificities of annexins IV, V, and VI by affinity
      chromatography and solid phase assays. Annexin IV was found to bind in a calcium
      dependent manner to all the GAG columns tested. Annexin V bound to heparin and
      heparan sulfate columns but not to chondroitin sulfate columns. Annexin VI was
      adsorbed to heparin and heparan sulfate columns in a calcium-independent manner,
      and to chondroitin sulfate columns in a calcium-dependent manner. An N-terminal
      half fragment (A6NH) and a C-terminal half fragment (A6CH) of annexin VI, each
      containing four units, were prepared by digestion with V8 protease and examined
      for GAG binding activities. A6NH bound to heparin in the presence of calcium but
      not to chondroitin sulfate C, whereas A6CH bound to heparin calcium-independently
      and to chondroitin sulfate C calcium-dependently. The results showed that annexin
      IV, V, and VI have different GAG binding properties. Some annexins have been
      reported to be detected not only in the cytoplasm but also on the cell surface or
      in extracellular components. The findings suggest that the some annexins function
      as recognition elements for GAGs in extracellular space.

PMID- 9545338
TI  - Mechanisms for the processing of a frozen topoisomerase-DNA conjugate by human
      cell-free extracts.
AB  - The metabolic fate of covalently linked DNA-protein complexes (cross-links) is
      not clearly understood. Our aim was to investigate the processing of protein-DNA
      cross-links by cellular enzymes. As an example of a DNA-protein cross-link, we
      have constructed frozen topoisomerase-DNA conjugates and investigated their
      processing by human cell-free extracts. A suicide DNA substrate was constructed
      that upon reaction with vaccinia type I topoisomerase yielded a highly stable
      covalent DNA-protein cross-link. When this conjugate was treated with human
      nuclear or whole cell extracts, two sites of DNA breakpoints were detected: one
      set of double-stranded breaks occurred close to the 3' side of the topoisomerase
      (topo) conjugation site, and there was another set of nicks about 30 nucleotides
      3' to the topo site. The double-stranded breaks were not made by extracts from
      xeroderma pigmentosum group A mutant cells, suggesting that the xeroderma
      pigmentosum group A damage recognition protein may be required for the occurrence
      of DNA breakage. In addition to these DNA breakage reactions, there was an
      activity that resulted in the delinking of the frozen topoisomerase (or
      proteolytic fragments thereof) from the DNA substrate, which was followed by a
      ligation step that restored the continuity of the broken DNA strand at the
      erstwhile topo attachment site. We suggest that frozen topoisomerase-DNA
      conjugates (and perhaps other types of covalent DNA-protein complexes) are
      processed by multiple pathways that may involve the cleavage of the DNA in the
      covalent protein-DNA complex and/or enzymatic delinking followed by ligation of
      the broken DNA ends. These processes may represent the "repair" of DNA-protein
      cross-links.

PMID- 9545339
TI  - Characterization of V3 loop-Pseudomonas exotoxin chimeras. Candidate vaccines for
      human immunodeficiency virus-1.
AB  - To develop a candidate vaccine for human immunodeficiency virus, type 1 (HIV-1),
      chimeric proteins were constructed by inserting sequences derived from the V3
      loop of gp120 into a nontoxic form of Pseudomonas exotoxin (PE). Inserts of 14 or
      26 amino acids, constrained by a disulfide bond, were introduced between domains
      II and III of PE. V3 loop-toxin proteins expressed in Escherichia coli and
      corresponding to either MN (subtype B) or Thai (subtype E) strains, were
      recognized by strain-specific monoclonal anti-gp120 antibodies. When loop
      sequences were introduced into an enzymatically active form of the toxin, there
      was no loss of toxin-mediated cell killing, suggesting that these sequences were
      co-transported to the cytosol. Sera from rabbits injected with nontoxic PE-V3
      loop chimeras were reactive for strain-specific gp120s in Western blots,
      immunocapture assays, enzyme-linked immunosorbent assays, and neutralized HIV-1
      infectivity. Since toxin vectors were designed to receive oligonucleotide
      duplexes encoding any V3 loop sequence, this approach should allow for the
      production of V3 loop-toxin chimeras corresponding to multiple HIV isolates.

PMID- 9545340
TI  - Involvement of Sp1 elements in the promoter activity of the alpha1-proteinase
      inhibitor gene.
AB  - The transcripts of the alpha1-proteinase inhibitor in the cornea are different
      from those in hepatocytes and monocytes, suggesting that alpha1-proteinase
      inhibitor gene transcription may respond to different cell-specific regulatory
      mechanisms. Although information on alpha1-proteinase inhibitor gene structure
      has been obtained, little is known regarding the cis- and trans-acting factors
      that regulate its expression. In this study, we cloned and sequenced a 2. 7
      kilobase 5'-flanking region upstream from the corneal transcription initiation
      site of the gene, demonstrated functional promoter activity, and identified the
      regulatory elements. Sequencing revealed that the 5'-flanking element was highly
      G/C-rich in regions proximal to the corneal transcription start site. DNase I
      footprinting located 10 potential Sp1-binding sites between nucleotides -1519 and
      +44. The putative promoter was functional in human corneal stromal cells, but not
      in human skin, scleral, and conjunctival fibroblasts, suggesting that the
      promoter may be corneal cell-specific. The promoter activity in the corneal cells
      was repressed when Sp1 was coexpressed. In the cornea-thinning disease
      keratoconus, down-regulation of the alpha1-proteinase inhibitor gene and
      increased Sp1 expression have both been demonstrated. The current results suggest
      that down-regulation of the inhibitor in keratoconus corneas may be related
      directly to overexpression of the Sp1 gene. This information may help elucidate
      the molecular pathways leading to the altered alpha1-proteinase inhibitor
      expression in keratoconus.

PMID- 9545341
TI  - Inhibition of the mitogen-activated protein kinase pathway triggers B16 melanoma
      cell differentiation.
AB  - In B16 melanoma cells, mitogen-activated protein (MAP) kinases are activated
      during cAMP-induced melanogenesis (Englaro, W., Rezzonico, R., Durand-Clement,
      M., Lallemand, D., Ortonne, J. P., and Ballotti, R. (1995) J. Biol. Chem. 270,
      24315-24320). To establish the role of the MAP kinases in melanogenesis, we
      studied the effects of a specific MAP kinase kinase (MEK) inhibitor PD 98059 on
      different melanogenic parameters. We showed that PD 98059 inhibits the activation
      of MAP kinase extracellular signal-regulated kinase 1 by cAMP, but does not
      impair the effects of cAMP either on the morphological differentiation,
      characterized by an increase in dendrite outgrowth, or on the up-regulation of
      tyrosinase that is the key enzyme in melanogenesis. On the contrary, PD 98059
      promotes by itself cell dendricity and increases the tyrosinase amount and
      activity. Moreover, down-regulation of the MAP kinase pathway by PD 98059, or
      with dominant negative mutants of p21(ras) and MEK, triggers a stimulation of the
      tyrosinase promoter activity and enhances the effect of cAMP on this parameter.
      Conversely, activation of the MAP kinase pathway, using constitutive active
      mutants of p21(ras) and MEK, leads to an inhibition of basal and cAMP-induced
      tyrosinase gene transcription. These results demonstrate that the MAP kinase
      pathway activation is not required for cAMP-induced melanogenesis. Furthermore,
      the inhibition of this pathway induces B16 melanoma cell differentiation, while a
      sustained activation impairs the melanogenic effect of cAMP-elevating agents.

PMID- 9545342
TI  - A cyclic AMP response element in the angiotensin-converting enzyme gene and the
      transcription factor CREM are required for transcription of the mRNA for the
      testicular isozyme.
AB  - The angiotensin-converting enzyme (ACE) gene produces two mRNA species from
      tissue-specific promoters. The transcription start site of the mRNA for the
      smaller testicular isozyme (ACET) is located within an intron of the larger
      transcription unit that encodes the pulmonary isozyme (ACEP).We have previously
      demonstrated that a 298-base pair DNA fragment, 5' to the rabbit ACET mRNA
      transcription initiation site, can activate the testicular expression of a
      transgenic reporter gene. In the current study, using the same transgenic
      reporter system, we identified a putative cyclic AMP response element present
      within this DNA fragment to be absolutely essential for transcriptional
      activation. Moreover, we observed that ACET mRNA was not expressed in the testes
      of mice homozygous for a null mutation in the transcription factor CREM. However,
      in the same mice, ACEP mRNA was abundantly expressed in the lung. Our
      observations indicate that ACET mRNA expression in the testes is regulated by the
      putative cyclic AMP response element present 5' to the transcription start site
      and the corresponding transcription factor CREM.

PMID- 9545343
TI  - Characterization of RNA strand displacement synthesis by Moloney murine leukemia
      virus reverse transcriptase.
AB  - The RNase H activity of reverse transcriptase (RT) is presumably required to
      cleave the RNA genome following minus strand synthesis to free the DNA for use as
      a template during plus strand synthesis. However, since RNA degradation by RNase
      H appears to generate RNA fragments too large to spontaneously dissociate from
      the minus strand, we have investigated the possibility that RNA displacement by
      RT during plus strand synthesis contributes to the removal of RNA fragments. By
      using an RNase H- mutant of Moloney murine leukemia virus (M-MuLV) RT, we
      demonstrate that the polymerase can displace long regions of RNA in hybrid duplex
      with DNA but that this activity is approximately 5-fold slower than DNA
      displacement and 20-fold slower than non-displacement synthesis. Furthermore, we
      find that although certain hybrid sequences seem nearly refractory to the
      initiation of RNA displacement, the same sequences may not significantly impede
      synthesis when preceded by a single-stranded gap. We find that the rate of RNA
      displacement synthesis by wild-type M-MuLV RT is significantly greater than that
      of the RNase H- RT but remains less than the rate of non-displacement synthesis.
      M-MuLV nucleocapsid protein increases the rates of RNA and DNA displacement
      synthesis approximately 2-fold, and this activity appears to require the zinc
      finger domain.

PMID- 9545344
TI  - Tissue plasminogen activator binding to the annexin II tail domain. Direct
      modulation by homocysteine.
AB  - Tissue plasminogen activator binds to endothelial cells via the calcium-regulated
      phospholipid-binding protein annexin II, an interaction that is inhibited by the
      prothrombotic amino acid homocysteine. We sought to identify the tissue
      plasminogen activator binding domain of annexin II and to determine the mechanism
      of its modulation by homocysteine. Tissue plasminogen activator binding to
      immobilized annexin II was inhibited by intact fluid phase annexin II but not by
      its "core" fragment (residues 25-339). Two overlapping "tail" peptides
      specifically blocked 65-75% of binding. Localization of the tissue plasminogen
      activator binding domain was confirmed upon specific inhibition by the
      hexapeptide LCKLSL (residues 7-12). Expressed C9G annexin II protein failed to
      support tissue plasminogen activator binding, while binding to C133G, C262G, and
      C335G was equivalent to that of wild type annexin II. Upon exposure to
      homocysteine, annexin II underwent a 135 +/- 4-Da increase in mass localizing
      specifically to Cys9 and a 60-66% loss in tissue plasminogen activator-binding
      capacity (I50 = 11 microM). Upon treatment of cultured endothelial cells with
      [35S]homocysteine, the dithiothreitol-sensitive label was recovered by
      immunoprecipitation with anti-annexin II IgG. These data provide a potential
      mechanism for the prothrombotic effect of homocysteine by demonstrating direct
      blockade of the tissue plasminogen activator binding domain of annexin II.

PMID- 9545345
TI  - Insulin receptor substrate-1 is the predominant signaling molecule activated by
      insulin-like growth factor-I, insulin, and interleukin-4 in estrogen receptor
      positive human breast cancer cells.
AB  - Because insulin-like growth factor-I (IGF-I), insulin, and interleukin-4 (IL-4)
      have known biological effects in breast cancer cells and signal through insulin
      receptor substrate (IRS) adaptor proteins, we examined the expression and
      function of IRS-1 and IRS-2 in breast tumors and cell lines. IRS-1 and IRS-2 were
      expressed by cell lines and primary breast tumor specimens. IGF-I, insulin, and
      IL-4 treatment of MCF-7 and ZR-75, and IGF-I treatment of T47-D breast cancer
      cells, resulted in much greater tyrosine phosphorylation of IRS-1 compared with
      IRS-2. Furthermore, IGF-I stimulated greater tyrosine phosphorylation of IRS-1
      than either insulin or IL-4. IGF-I treatment also enhanced association of the p85
      regulatory subunit of phosphatidylinositol 3-kinase with IRS-1 and stimulated
      increased enzymatic activity compared with IL-4 and insulin in all three cell
      lines. Similarly, mitogen-activated protein kinase activity was greater in IGF-I
      stimulated cells. To determine the functional significance of the activation of
      these pathways, we inhibited activation of phosphatidylinositol 3-kinase with
      wortmannin and mitogen-activated protein kinase with PD098059. Both compounds
      inhibited IGF-stimulated growth, suggesting that both pathways contributed to the
      mitogenic response to IGF-I. We conclude that IRS-1, and not IRS-2, is the
      predominant signaling molecule activated by IGF-I, insulin, and IL-4.
      Furthermore, enhanced tyrosine phosphorylation of IRS-1 by IGF-I, compared with
      either insulin or IL-4, is associated with greater activation of mitogenic
      downstream signaling pathways resulting in enhanced cell growth.

PMID- 9545346
TI  - Overexpression of C-terminal Src kinase homologous kinase suppresses activation
      of Lyn tyrosine kinase required for VLA5-mediated Dami cell spreading.
AB  - The Csk homologous kinase (Chk), which is co-expressed with C-terminal Src kinase
      (Csk) in hematopoietic cells, negatively regulates Src family kinases in vitro
      with selectivity toward Lyn but not c-Src in platelets. To explore the role of
      Src family kinases in hematopoietic cell adhesion, we overexpressed Chk in the
      megakaryocytic cell line Dami and established clones exhibiting a 10-fold
      increase in the amount of Chk. Overexpression of Chk was found to suppress VLA5
      integrin-mediated cell spreading, but not cell attachment, throughout fibronectin
      (FN) stimulation. Deletion and point mutagenesis analyses of Chk showed that this
      suppression was dependent upon both the SH3 domain, which is responsible for
      membrane anchoring, and kinase activity. FN-induced cell spreading accompanied a
      sustained increase in Lyn activity with coincidental kinetics and the activation
      of Lyn was also suppressed by overexpression of Chk but not a Chk mutant lacking
      the SH3 domain. Expression of a truncated Lyn mutant lacking the kinase domain
      inhibited both cell spreading and Lyn activation upon stimulation with FN. These
      results suggest that sustained activation of Lyn, which is regulated by membrane
      anchored Chk, plays a crucial role in VLA5-mediated cell spreading but not cell
      attachment to a FN substrate.

PMID- 9545347
TI  - Molecular cloning and characterization of a novel human classic cadherin
      homologous with mouse muscle cadherin.
AB  - We used a novel cDNA cloning method based on the cadherin-beta-catenin protein
      interaction and identified a new human classic-type cadherin, which we named
      cadherin-15, from adult brain and skeletal muscle cDNA libraries. Sequence
      analysis revealed that this cadherin was closely related to mouse muscle cadherin
      and seemed to be its human counterpart. However, its deduced amino acid sequence
      differed from that of mouse muscle cadherin in that it had an extra 31-amino acid
      sequence at its C terminus that has been found neither in mouse muscle cadherin
      nor in any other known classic cadherin. Analysis of cadherin-15 protein
      expressed in L fibroblasts showed that it was cleaved proteolytically, expressed
      on the cell surfaces as a mature form of about 124-kDa, and functioned as a cell
      cell adhesion molecule in a homophilic and specific manner, but Ca2+ did not
      protect it against degradation by trypsin. Our findings also suggest that
      cadherin-15 mediates cell-cell adhesion with a binding strength comparable to
      that of E-cadherin.

PMID- 9545348
TI  - The identification, purification, and characterization of CooJ. A nickel-binding
      protein that is co-regulated with the Ni-containing CO dehydrogenase from
      Rhodospirillum rubrum.
AB  - CooJ, a nickel-binding protein from the CO dehydrogenase system of Rhodospirillum
      rubrum, was purified by immobilized metal affinity chromatography. CooJ is a CO
      induced protein predicted to contain a nickel binding motif composed of 16
      histidine residues in the final 34 amino acids of the 12.5-kDa protein. When
      cells grown in the presence of CO were fractionated on an immobilized metal
      affinity chromatography column and analyzed by SDS-polyacrylamide gel
      electrophoresis, the major protein observed in the effluent migrated at an
      apparent molecular mass of 19 kDa. The 19-kDa protein was absent in extracts of
      cells grown in the absence of CO and the mutant strain, UR294, which lacks a
      functional cooJ gene. N-terminal sequence analysis confirmed that the 19-kDa
      protein is the product of the cooJ gene. Purified CooJ was shown to bind four
      nickel atoms per CooJ monomer with a Kd of 4.3 microM. Other divalent metals
      competed with the following order of affinity and corresponding Ki: Zn2+ (5
      microM) > Cd2+ (19 microM) > Co2+ (23 microM) > Cu2+ (122 microM). CooJ
      chromatographed on a calibrated Superose 12 gel filtration column eluted at 39
      kDa, a position consistent with a multimeric native molecular mass for CooJ.

PMID- 9545350
TI  - Properties of pervanadate and permolybdate. Connexin43, phosphatase inhibition,
      and thiol reactivity as model systems.
AB  - Pervanadate and permolybdate are irreversible protein-tyrosine phosphatase
      inhibitors, with IC50 values of 0.3 and 20 microM, respectively, in intact cells.
      Maximal inhibition was obtained within 1 min at higher concentrations of the
      compounds. They induced prominent changes in the phosphorylation status of the
      gap junction protein, connexin43. These effects were utilized as model systems to
      assess the stability and inactivation of the compounds. Although the concentrated
      stock solutions were relatively stable, the diluted compounds were unstable. The
      biological activity had decreased to 20-30% after 6 h of incubation in a
      phosphate buffer, 1 h in phosphate buffer with 10% fetal calf serum, and 1-3
      minutes in culture medium. Thiols reacted rapidly with the compounds and
      inactivated them (initial reaction rates with cysteine: permolybdate >
      pervanadate > H2O2). Catalase inactivated the compounds, and permolybdate was the
      more sensitive. The cells inactivated permolybdate faster than pervanadate.
      Cellular inactivation of permolybdate, and to a lesser degree pervanadate,
      appeared to be partly dependent on catalase and thiols. However, a general
      decrease in cellular thiols was not the mediator of the biological effects of
      pervanadate or permolybdate. Mathematical modeling of the thiol reactivity
      suggested that monoperoxovanadate at maximum could possess 20% of the biological
      activity of diperoxovanadate.

PMID- 9545349
TI  - Enzymatic processing of uracil glycol, a major oxidative product of DNA cytosine.
AB  - A major stable oxidation product of DNA cytosine is uracil glycol (Ug). Because
      of the potential of Ug to be a strong premutagenic lesion, it is important to
      assess whether it is a blocking lesion to DNA polymerase as is its structural
      counterpart, thymine glycol (Tg), and to evaluate its pairing properties. Here, a
      series of oligonucleotides containing Ug or Tg were prepared and used as
      templates for a model enzyme, Escherichia coli DNA polymerase I Klenow fragment
      (exo-). During translesion DNA synthesis, Ug was bypassed more efficiently than
      Tg in all sequence contexts examined. Furthermore, only dAMP was incorporated
      opposite template Ug and Tg and the kinetic parameters of incorporation showed
      that dAMP was inserted opposite Ug more efficiently than opposite Tg. Ug opposite
      G and A was also recognized and removed in vitro by the E. coli DNA repair
      glycosylases, endonuclease III (endo III), endonuclease VIII (endo VIII), and
      formamidopyrimidine DNA glycosylase. The steady state kinetic parameters
      indicated that Ug was a better substrate for endo III and formamidopyrimidine DNA
      glycosylase than Tg; for endonuclease VIII, however, Tg was a better substrate.

PMID- 9545351
TI  - The sister of P-glycoprotein represents the canalicular bile salt export pump of
      mammalian liver.
AB  - Canalicular secretion of bile salts is a vital function of the vertebrate liver,
      yet the molecular identity of the involved ATP-dependent carrier protein has not
      been elucidated. We cloned the full-length cDNA of the sister of P-glycoprotein
      (spgp; Mr approximately 160,000) of rat liver and demonstrated that it functions
      as an ATP-dependent bile salt transporter in cRNA injected Xenopus laevis oocytes
      and in vesicles isolated from transfected Sf9 cells. The latter demonstrated a 5
      fold stimulation of ATP-dependent taurocholate transport as compared with
      controls. This spgp-mediated taurocholate transport was stimulated solely by ATP,
      was inhibited by vanadate, and exhibited saturability with increasing
      concentrations of taurocholate (Km approximately 5 microM). Furthermore, spgp
      mediated transport rates of various bile salts followed the same order of
      magnitude as ATP-dependent transport in canalicular rat liver plasma membrane
      vesicles, i.e. taurochenodeoxycholate > tauroursodeoxycholate = taurocholate >
      glycocholate = cholate. Tissue distribution assessed by Northern blotting
      revealed predominant, if not exclusive, expression of spgp in the liver, where it
      was further localized to the canalicular microvilli and to subcanalicular
      vesicles of the hepatocytes by in situ immunofluorescence and immunogold labeling
      studies. These results indicate that the sister of P-glycoprotein is the major
      canalicular bile salt export pump of mammalian liver.

PMID- 9545352
TI  - Modulation of E2F activity via signaling through surface IgM and CD40 receptors
      in WEHI-231 B lymphoma cells.
AB  - Stimulation of the phenotypically immature B cell lymphoma WEHI-231 with anti-IgM
      induces G1 arrest followed by apoptotic cell death, which can be reversed by
      stimulation via the CD40 receptor. Here, we show that cells expressing bcl-xL
      (WEHI-bcl-xL) arrest at G0/G1 following culture with anti-IgM but do not undergo
      apoptosis. These arrested cells can be induced to reenter the cell cycle by
      ligation of CD40. We have therefore used these cells as a model to study the
      regulation of the transcription factor E2F, which is critically involved in
      transit through the cell cycle. We found that anti-IgM treatment induces the
      appearance of an inhibitory DNA binding complex containing the pRB-related pocket
      protein p130 together with E2F and a concomitant decrease in "free" E2F,
      consisting of E2F1 and its partner DP1; these effects were reversed following
      stimulation via CD40. These changes in free E2F levels were regulated by changes
      in E2F1 gene transcription, which is at least partly a result of control of E2F1
      promoter activity through its E2F binding sites. Transient transfection
      experiments showed that either E2F1 or the viral oncoprotein E1A, which
      sequesters pocket proteins, including p130, overcame anti-IgM-induced cell cycle
      arrest in WEHI-bcl-xL. Taken together, these results indicate that in WEHI-231
      sIgM ligation induces the accumulation of hypophosphorylated p130 with consequent
      inhibition of E2F1 gene transcription and cell cycle arrest. Conversely, ligation
      of CD40 causes hyperphosphorylation of p130, thereby releasing the repression of
      E2F1 and other E2F-regulated genes, enabling the cells to reenter the cycle.
      These results, therefore, provide novel insights into the mechanisms whereby
      antigen receptors on immature B cells deliver inhibitory signals (leading to
      negative selection of self-reactive B cells) and how these signals can be
      modulated by positive signals generated via CD40.

PMID- 9545353
TI  - Comparison of promoters for the murine and human P-selectin genes suggests
      species-specific and conserved mechanisms for transcriptional regulation in
      endothelial cells.
AB  - P-selectin, an adhesion receptor for leukocytes, is constitutively expressed in
      megakaryocytes and endothelial cells. Tumor necrosis factor-alpha (TNF-alpha) or
      lipopolysaccharide (LPS) increases synthesis of P-selectin in murine but not in
      human endothelial cells. To identify potential species-specific and conserved
      mechanisms for regulation of expression of P-selectin, we cloned the 5'-flanking
      region of the murine P-selectin gene and compared its features with those
      previously reported for the human gene. The murine and human genes shared
      conserved Stat-like, Hox, Ets, GATA, and GT-IIC elements. In the murine gene, a
      conserved GATA element bound to GATA-2 and functioned as a positive regulatory
      element, whereas a conserved Ets element bound to GA-binding protein and
      functioned as a negative regulatory element. Significantly, the murine P-selectin
      gene had several features not found in the human gene. These included an
      insertion from -987 to -649 that contained tandem GATA and tandem AP1-like
      sequences, which resembled enhancers in beta-globin locus control regions. Both
      tandem elements bound specifically to nuclear proteins. The murine gene lacked
      the unique kappaB site specific for p50 or p52 homodimers found in the human
      gene. Instead, it contained two tandem kappaB elements and a variant activating
      transcription factor/cAMP response element site, which closely resembled sites in
      the E-selectin gene that are required for TNF-alpha- or LPS-inducible expression.
      TNF-alpha or LPS augmented expression of a reporter gene driven by the murine,
      but not the human, P-selectin promoter in transfected endothelial cells.
      Deletional analysis of the murine 5'-flanking region revealed several sequences
      that were required for either constitutive or inducible expression. These data
      suggest that both species-specific and conserved mechanisms regulate
      transcription of the human and murine P-selectin genes.

PMID- 9545354
TI  - Tumor necrosis factor-alpha- or lipopolysaccharide-induced expression of the
      murine P-selectin gene in endothelial cells involves novel kappaB sites and a
      variant activating transcription factor/cAMP response element.
AB  - Tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) increases
      expression of the P-selectin gene in murine, but not in human, endothelial cells.
      These mediators augment expression of a reporter gene driven by the murine, but
      not the human, P-selectin promoter in transfected endothelial cells. The regions
      from -593 to -474 and from -229 to -13 in the murine P-selectin promoter are
      required for TNF-alpha or LPS to stimulate reporter gene expression. Within these
      regions, we identified two tandem kappaB elements, a reverse-oriented kappaB site
      and a variant activating transcription factor/cAMP response element (ATF/CRE),
      that participate in TNF-alpha- or LPS-induced expression. The tandem kappaB
      elements bound to NF-kappaB heterodimers and p65 homodimers, the reverse-oriented
      kappaB site bound to p65 homodimers, and the variant ATF/CRE bound to nuclear
      proteins that included activating transcription factor-2. Mutations in each
      individual element eliminated binding to nuclear proteins and decreased by 20-60%
      the TNF-alpha- or LPS-induced expression of a reporter gene driven by the murine
      P-selectin promoter in transfected endothelial cells. Simultaneous mutations of
      all elements further decreased, but did not abolish, induced expression. Co
      overexpression of p50 and p65 enhanced murine P-selectin promoter activity in a
      kappaB site-dependent manner. These data indicate that the kappaB sites and the
      variant ATF/CRE are required for TNF-alpha or LPS to optimally induce expression
      of the murine P-selectin gene. The presence of these elements in the murine, but
      not the human, P-selectin gene may explain in part why TNF-alpha or LPS
      stimulates transcription of P-selectin in a species-specific manner.

PMID- 9545355
TI  - Absence of soluble leptin receptor in plasma from dbPas/dbPas and other db/db
      mice.
AB  - The leptin receptor (Ob-R) is alternatively spliced into at least five different
      RNAs designated Ob-R(a-e). Ob-R(a-d) predict receptors with a single
      transmembrane domain, and Ob-Re predicts a secreted form of the receptor. The
      presence of an approximately 120-kDa soluble leptin receptor in mouse plasma was
      confirmed by precipitation with leptin-Sepharose beads followed by immunobloting
      with anti-leptin receptor antibodies. The soluble leptin receptor is larger than
      that predicted by the primary sequence. Deglycosylation of the receptor with
      peptide N:glycosidase F results in a decrease in molecular mass to a size
      consistent with that of the primary sequence. The secreted receptor was present
      in plasma from wild type mice but was truncated in plasma from db3J/db3J and
      absent in dbPas/dbPas plasma. Although db3J/db3J mice are known to have a
      frameshift mutation at amino acid 625, the basis for the mutation in dbPas/dbPas
      mice was not known. Further studies indicated that dbPas/dbPas mice carry a
      duplication of exons 4 and 5 of Ob-R. This mutation introduces a premature stop
      codon into the protein at amino acid 281. The absence of Ob-R in db3J/db3J and
      dbPas/dbPas mice confirm the identify of the 120-kDa plasma protein as Ob-Re.

PMID- 9545356
TI  - Ten-year risk of false positive screening mammograms and clinical breast
      examinations.
AB  - BACKGROUND: The cumulative risk of a false positive result from a breast-cancer
      screening test is unknown. METHODS: We performed a 10-year retrospective cohort
      study of breast-cancer screening and diagnostic evaluations among 2400 women who
      were 40 to 69 years old at study entry. Mammograms or clinical breast
      examinations that were interpreted as indeterminate, aroused a suspicion of
      cancer, or prompted recommendations for additional workup in women in whom breast
      cancer was not diagnosed within the next year were considered to be false
      positive tests. RESULTS: A total of 9762 screening mammograms and 10,905
      screening clinical breast examinations were performed, for a median of 4
      mammograms and 5 clinical breast examinations per woman over the 10-year period.
      Of the women who were screened, 23.8 percent had at least one false positive
      mammogram, 13.4 percent had at least one false positive breast examination, and
      31.7 percent had at least one false positive result for either test. The
      estimated cumulative risk of a false positive result was 49.1 percent (95 percent
      confidence interval, 40.3 to 64.1 percent) after 10 mammograms and 22.3 percent
      (95 percent confidence interval, 19.2 to 27.5 percent) after 10 clinical breast
      examinations. The false positive tests led to 870 outpatient appointments, 539
      diagnostic mammograms, 186 ultrasound examinations, 188 biopsies, and 1
      hospitalization. We estimate that among women who do not have breast cancer, 18.6
      percent (95 percent confidence interval, 9.8 to 41.2 percent) will undergo a
      biopsy after 10 mammograms, and 6.2 percent (95 percent confidence interval, 3.7
      to 11.2 percent) after 10 clinical breast examinations. For every 100 dollars
      spent for screening, an additional 33 dollars was spent to evaluate the false
      positive results. CONCLUSIONS: Over 10 years, one third of women screened had an
      abnormal test result that required additional evaluation, even though no breast
      cancer was present. Techniques are needed to decrease false positive results
      while maintaining high sensitivity. Physicians should educate women about the
      risk of a false positive result from a screening test for breast cancer.

PMID- 9545357
TI  - Quality of life and clinical outcomes in elderly patients treated with
      ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in
      the Elderly Investigators.
AB  - BACKGROUND: Standard clinical practice permits the use of either single-chamber
      ventricular pacemakers or dual-chamber pacemakers for most patients who require
      cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber
      pacemakers are believed to be more physiologic. However, it is not known whether
      either type of pacemaker results in superior clinical outcomes. METHODS: The
      Pacemaker Selection in the Elderly study was a 30-month, single-blind,
      randomized, controlled comparison of ventricular pacing and dual-chamber pacing
      in 407 patients 65 years of age or older in 29 centers. Patients received a dual
      chamber pacemaker that had been randomly programmed to either ventricular pacing
      or dual-chamber pacing. The primary end point was health-related quality of life
      as measured by the 36-item Medical Outcomes Study Short-Form General Health
      Survey. RESULT: The average age of the patients was 76 years (range, 65 to 96),
      and 60 percent were men. Quality of life improved significantly after pacemaker
      implantation (P<0.001), but there were no differences between the two pacing
      modes in either the quality of life or prespecified clinical outcomes (including
      cardiovascular events or death). However, 53 patients assigned to ventricular
      pacing (26 percent) were crossed over to dual-chamber pacing because of symptoms
      related to the pacemaker syndrome. Patients with sinus-node dysfunction, but not
      those with atrioventricular block, had moderately better quality of life and
      cardiovascular functional status with dual-chamber pacing than with ventricular
      pacing. Trends of borderline statistical significance in clinical end points
      favoring dual-chamber pacing were observed in patients with sinus-node
      dysfunction, but not in those with atrioventricular block. CONCLUSION: The
      implantation of a permanent pacemaker improves health-related quality of life.
      However, the quality-of-life benefits associated with dual-chamber pacing as
      compared with ventricular pacing are observed principally in the subgroup of
      patients with sinus-node dysfunction.

PMID- 9545358
TI  - A comparison of recombinant urokinase with vascular surgery as initial treatment
      for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial
      Surgery (TOPAS) Investigators.
AB  - BACKGROUND: Recent controlled trials suggest that thrombolytic therapy may be an
      effective initial treatment for acute arterial occlusion of the legs. A major
      potential benefit of initial thrombolytic therapy is that limb ischemia can be
      managed with less invasive interventions. METHODS: In this randomized,
      multicenter trial conducted at 113 North American and European sites, we compared
      vascular surgery (e.g., thrombectomy or bypass surgery) with thrombolysis by
      catheter-directed intraarterial recombinant urokinase; all patients (272 per
      group) had had acute arterial obstruction of the legs for 14 days or less.
      Infusions were limited to a period of 48 hours (mean [+/-SE], 24.4+/-0.86), after
      which lesions were corrected by surgery or angioplasty if needed. The primary end
      point was the amputation-free survival rate at six months. RESULTS: Final
      angiograms, which were available for 246 patients treated with urokinase,
      revealed recanalization in 196 (79.7 percent) and complete dissolution of
      thrombus in 167 (67.9 percent). Both treatment groups had similar significant
      improvements in mean ankle-brachial blood-pressure index. Amputation-free
      survival rates in the urokinase group were 71.8 percent at six months and 65.0
      percent at one year, as compared with respective rates of 74.8 percent and 69.9
      percent in the surgery group; the 95 percent confidence intervals for the
      differences were -10.5 to 4.5 percentage points at six months (P=0.43) and -12.9
      to 3.1 percentage points at one year (P=0.23). At six months the surgery group
      had undergone 551 open operative procedures (excluding amputations), as compared
      with 315 in the thrombolysis group. Major hemorrhage occurred in 32 patients in
      the urokinase group (12.5 percent) as compared with 14 patients in the surgery
      group (5.5 percent) (P= 0.005). There were four episodes of intracranial
      hemorrhage in the urokinase group (1.6 percent), one of which was fatal. By
      contrast, there were no episodes of intracranial hemorrhage in the surgery group.
      CONCLUSIONS: Despite its association with a higher frequency of hemorrhagic
      complications, intraarterial infusion of urokinase reduced the need for open
      surgical procedures, with no significantly increased risk of amputation or death.

PMID- 9545359
TI  - A multicenter trial of two dexamethasone regimens in ventilator-dependent
      premature infants.
AB  - BACKGROUND: Ventilator-dependent premature infants are often treated with
      dexamethasone. However, the optimal timing of therapy is unknown. METHODS: We
      compared the benefits and hazards of initiating dexamethasone therapy at two
      weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth
      weight infants (501 to 1500 g) who had respiratory index scores (mean airway
      pressure x the fraction of inspired oxygen) of 52.4 at two weeks of age. One
      hundred eighty-two infants received dexamethasone for two weeks followed by
      placebo for two weeks, and 189 infants received placebo for two weeks followed by
      either dexamethasone (those with a respiratory-index score of > or =2.4 on
      treatment day 14) or additional placebo for two weeks. Dexamethasone was given at
      a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally
      for five days, and the dose was then tapered. RESULTS: The median time to
      ventilator independence was 36 days in the dexamethasone-placebo group and 37
      days in the placebo-dexamethasone group. The incidences of chronic lung disease
      (defined as the need for oxygen supplementation at 36 weeks' postconceptional
      age) were 66 percent and 67 percent, respectively. Dexamethasone was associated
      with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95
      percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9;
      95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group,
      elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2
      to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head
      growth (P< 0.001) in both groups. CONCLUSIONS: Treatment of ventilator-dependent
      premature infants with dexamethasone at two weeks of age is more hazardous and no
      more beneficial than treatment at four weeks of ages.

PMID- 9545360
TI  - Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy.
AB  - BACKGROUND: Globoid-cell leukodystrophy is caused by a deficiency of
      galactocerebrosidase, which results in progressive central nervous system
      deterioration. We investigated whether allogeneic hematopoietic stem-cell
      transplantation can provide a source of leukocyte galactocerebrosidase and
      thereby prevent the decline of central nervous system function in patients with
      the disease. METHODS: Five children with globoid-cell leukodystrophy (one with
      the infantile type and four with late-onset disease) were treated with allogeneic
      hematopoietic stem-cell transplantation. Measurement of leukocyte
      galactocerebrosidase levels, neurologic examinations, neuropsychological tests,
      magnetic resonance imaging of the central nervous system, cerebrospinal fluid
      protein assays, and neurophysiologic measurements were performed before and after
      transplantation, with follow-up ranging from one to nine years. RESULTS:
      Engraftment of donor-derived hematopoietic cells occurred in all patients and was
      followed by restoration of normal leukocyte galactocerebrosidase levels. In the
      four patients with late-onset disease, the central nervous system deterioration
      was reversed, and in the patient with the infantile form of the disease, signs
      and symptoms have not appeared. Magnetic resonance imaging showed a decrease in
      signal intensity in the three patients with late-onset disease who were assessed
      both before and after transplantation. Abnormalities in cerebrospinal fluid total
      protein levels were corrected in three patients with late-onset disease and
      substantially reduced in the patient with the infantile form. CONCLUSIONS:
      Central nervous system manifestations of globoid-cell leukodystrophy can be
      reversed by allogeneic hematopoietic stem-cell transplantation.

PMID- 9545361
TI  - Images in clinical medicine. Unilateral livedo reticularis.

PMID- 9545362
TI  - Drugs in pregnancy.

PMID- 9545364
TI  - Benefit and harm associated with screening for breast cancer.

PMID- 9545365
TI  - Do patients prefer physiologic pacing?

PMID- 9545366
TI  - Thrombolysis for acute arterial occlusion of the legs.

PMID- 9545367
TI  - Should all people over the age of 50 have regular fecal occult-blood tests?
      Postpone population screening until problems are solved.

PMID- 9545368
TI  - Equine infectious anemia virus transactivator is a homeodomain-type protein.
AB  - Lentiviral transactivator (Tat) proteins are essential for viral replication. Tat
      proteins of human immunodeficiency virus type 1 and bovine immunodeficiency virus
      form complexes with their respective RNA targets (Tat responsive element, TAR),
      and specific binding of the equine anemia virus (EIAV) Tat protein to a target
      TAR RNA is suggested by mutational analysis of the TAR RNA. Structural data on
      equine infectious anemia virus Tat protein reveal a helix-loop-helix-turn-helix
      limit structure very similar to homeobox domains that are known to bind
      specifically to DNA. Here we report results of gel-shift and footprinting
      analysis as well as fluorescence and nuclear magnetic resonance spectroscopy
      experiments that clearly show that EIAV Tat protein binds to DNA specifically at
      the long terminal repeat Pu.1 (GTTCCTGTTTT) and AP-1 (TGACGCG) sites, and thus
      suggest a common mechanism for the action of some of the known lentiviral Tat
      proteins via the AP-1 initiator site. Complex formation with DNA induces specific
      shifts of the proton NMR resonances originating from amino acids in the core and
      basic domains of the protein.

PMID- 9545369
TI  - Tandem 5'-GA:GA-3' mismatches account for the high stability of the fold-back
      structures formed by the centromeric Drosophila dodeca-satellite.
AB  - The centromeric dodeca-satellite of Drosophila forms unusual DNA structures in
      which its purine-rich strand (GTACGGGACCGA)n folds into very stable
      intramolecular hairpins. These intramolecular hairpins contain groups of tandem
      5'-GA:GA-3' mismatches that, as judged by gel electrophoresis analysis and UV
      melting studies, have a determinant contribution to their stability. Duplexes of
      the dodeca-satellite purine-rich strand, carrying tandem 5'-GA:GA-3' mismatches,
      are as stable as equivalent fully Watson-Crick duplexes containing tandem 5'
      TA:TA-3' Watson-Crick pairs in place of the non-Watson-Crick G.A pairs. On the
      other hand, duplexes carrying any of the other three possible tandem combinations
      of purine.purine mismatches, including G.A pairs on the opposite orientation 5'
      AG:AG-3', are very unstable. The high stability of the dodeca-satellite hairplus
      suggests that the tandem G.A pairs are on the sheared configuration although they
      are found within the less favourable 5'-G-(G-A)-C-3' sequence context. Other
      centromeres DNA sequences, including the AAGAG satellite of Drosophila and the
      mammalian CENP-B box sequence, have the potential of forming intramolecular
      hairpins stabilised by similar purine.purine interactions.

PMID- 9545370
TI  - Human T cell cyclophilin18 binds to thiol-specific antioxidant protein Aop1 and
      stimulates its activity.
AB  - Cyclophilins (CyPs) define a family of proteins binding to the immunosuppressive
      drug cyclosporin A (CsA). They are evolutionary highly conserved proteins being
      present in both pro- and eukaryotes and in different subcellular locations. CyPs
      possess enzymatic activity, namely peptidyl-prolyl cis-trans isomerase (PPIase)
      activity and are involved in cellular protein folding and protein interactions.
      Here we describe a novel interaction of human T cell cyclophilin18 (hCyP18).
      Abundant cytosolic hCyP18 binds to the thiol-specific antioxidant protein Aop1
      and stimulates its enzymatic activity. Aop1 belongs to a family of proteins
      thought to be involved in defense of oxidative stress. The interaction of both
      proteins seem to be specific, since other PPIases do not have any stimulatory
      effect on Aop1.

PMID- 9545371
TI  - Plugging interactions of HAP2 pentamer into the distal end of flagellar filament
      revealed by electron microscopy.
AB  - Bacterial flagellum has a cap structure tightly attached to its distal end. The
      cap is an oligomeric assembly of HAP2 protein (also called FliD) and plays an
      essential role in the filament growth in vivo by preventing flagellin monomers
      from leaking out without polymerization. Electron micrographs of the HAP2 complex
      formed in solution showed exclusively a pentagonal shape, called "star-cap",
      which was thought to be the end-on view of the cap. The molecular mass roughly
      corresponded to a dodecamer of HAP2, and therefore a double-layered star-cap was
      modeled to be the cap. Here, we have observed the side view of the complex in
      electron micrographs. The images clearly show a rectangular shape, about 80 A
      wide and 180 A long, with a bipolar feature in its long axis, indicating that the
      complex is a bipolar pair of pentamers. A thin plate feature is identified at
      each end of the particle, which looks exactly like the one observed as the
      structure of the native filament cap. Together with the structure of the filament
      previously analyzed by electron cryomicroscopy, the results suggest that the cap
      is a pentamer with its thin plate exposed to the solvent and the other half
      plugged into the hole at the distal end of the filament, which is almost twice
      wider than its central channel. This also allows us to model the axial domain
      arrangement of flagellin subunit in the filament.

PMID- 9545372
TI  - Role of protein-induced bending in the specificity of DNA recognition: crystal
      structure of EcoRV endonuclease complexed with d(AAAGAT) + d(ATCTT).
AB  - The crystal structure of EcoRV endonuclease has been determined at 2. 1 A
      resolution complexed to two five-base-pair DNA duplexes each containing the
      cognate recognition half-site. The highly localized 50 degrees bend into the
      major groove seen at the center TA-step of the continuous GATATC site is
      preserved in this discontinuous DNA complex lacking the scissile phosphates.
      Thus, this crystal structure provides evidence that covalent constraints
      associated with a continuous target site are not essential to enzyme-induced DNA
      bending, even when these constraints are removed directly at the locus of the
      bend. The scissile phosphates are also absent in the crystal structure of EcoRV
      bound to the non-specific site TCGCGA, which shows a straight B-like
      conformation. We conclude that DNA bending by EcoRV is governed only by the
      sequence and is not influenced by the continuity of the phosphodiester backbone.
      Together with other data showing that cleavable non-cognate sites are bent, these
      results indicate that EcoRV bends non-cognate sites differing by one or two base
      pairs from GATATC, but does not bend non-specific sites that are less similar.
      Structural and thermodynamic considerations suggest that the sequence-dependent
      energy cost of DNA bending is likely to play an important role in determining the
      specificity of EcoRV. This differential cost is manifested at the binding step
      for bent non-cognate sequences and at the catalytic step for unbent non-specific
      sequences.

PMID- 9545373
TI  - Transcription activation at promoters carrying tandem DNA sites for the
      Escherichia coli cyclic AMP receptor protein: organisation of the RNA polymerase
      alpha subunits.
AB  - We have constructed a family of promoters carrying tandem DNA sites for the
      Escherichia coli cyclic AMP receptor protein (CRP), with one of the sites centred
      between base-pairs 41 and 42 upstream from the transcription start site, and the
      second site located further upstream. In vivo activity measurements show that the
      activity of these promoters is completely dependent on CRP and that, depending on
      the precise location, CRP bound at the upstream site increases transcription
      activation. Hydroxyl radical footprinting was exploited to investigate the
      binding of CRP and RNA polymerase holoenzyme (RNAP) to these promoters. The study
      shows that the C-terminal domains of the RNAP alpha subunits bind adjacent to the
      upstream CRP and that their precise positioning depends on the location of
      upstream-bound CRP. The C-terminal domains of the RNAP alpha subunits interact
      with both the upstream and downstream-bound CRP via activating region 1 of CRP.

PMID- 9545374
TI  - The arginine repressor of Escherichia coli K-12 makes direct contacts to minor
      and major groove determinants of the operators.
AB  - In order to gain further insight into the molecular mechanism of arginine
      dependent operator recognition by the hexameric Escherichia coli arginine
      repressor we have probed protein-DNA interactions in vitro and in vivo. We have
      extensively applied the chemical modification-protection and premodification
      interference approach to two operators, the natural operator overlapping the P2
      promoter of the carAB operon and a fully symmetrical consensus sequence. Backbone
      contacts were revealed by hydroxyl radical footprinting and phosphate ethylation
      interference. Base-specific contacts to purines and pyrimidines were revealed by
      methylation protection and premodification interference, KMnO4 and NH2OH.HCl
      specific modification of thymine and cytosine residues, base-removal
      (depurination and depyrimidation), and base substitution (uracil and inosine).
      Additional information on the groove specificity of repressor binding was
      obtained by small ligand binding interference (distamycin and methyl green). In
      vivo, we measured the effects on the repressibility of 24 single base-pair
      substitutions obtained by saturation mutagenesis of half an Arg box in the carAB
      operator. The results of these experiments point to the conclusion that a
      hexameric arginine repressor molecule covers four turns of the helix, makes base
      specific contacts to at least one guanine (G4 or G4') and two thymine (T3, T13',
      or T3', T13) residues in each one of four consecutive major grooves on one face
      of the helix and with four A-T/T-A base-pairs, comprising the adenine residues
      A9, 9', 12, 12' and the thymine residues T10, 10', 11, 11', in the two outermost
      minor grooves of the operator, on the very same face of the DNA molecule. The
      hydrophobic 5-methyl groups of four thymine residues (T3, 3', 13, 13') in each
      Arg box contribute to major groove-specific recognition via hydrophobic and/or
      van der Waals interactions. The importance of minor groove contacts was further
      supported by the drastic effect of distamycin binding interference. In vivo, the
      most pronounced drops in repressibility were occasioned by mutations at positions
      10 (A-->G or C), 11 (T-->A or G) and 12 (A-->G, T or C).

PMID- 9545375
TI  - ATP-independent DNA unwinding by the adenovirus single-stranded DNA binding
      protein requires a flexible DNA binding loop.
AB  - The adenovirus DNA binding protein (DBP) binds cooperatively to single-stranded
      (ss) DNA and stimulates both initiation and elongation of DNA replication. DBP
      forms protein filaments via a C-terminal arm that hooks into a neighbouring
      molecule. This multimerization is the driving force for ATP-independent DNA
      unwinding by DBP during elongation. Another conserved part of DBP forms an
      unstructured flexible loop that is probably directly involved in contacting DNA.
      By making appropriate deletion mutants that do not distort the overall DBP
      structure, the influence of the C-terminal arm and the flexible loop on the
      kinetics of ssDNA binding and on DNA replication was studied. Employing surface
      plasmon resonance we show that both parts of the protein are required for high
      affinity binding. Deletion of the C-terminal arm leads to an extremely labile DBP
      ssDNA complex indicating the importance of multimerization. The flexible loop is
      also required for optimal stability of the DBP-ssDNA complex, providing
      additional evidence that this region forms part of the ssDNA-binding surface of
      DBP. Both deletion mutants are still able to stimulate initiation of DNA
      replication but are defective in supporting elongation, which may be caused by
      the fact that both mutants have a reduced DNA unwinding activity. Surprisingly,
      mixtures containing both mutants do stimulate elongation. Mixing the purified
      mutant proteins leads to the formation of mixed filaments that have a higher
      affinity for ssDNA than homogeneous mutant filaments. These results provide
      evidence that the C-terminal arm and the flexible loop have distinct functions in
      unwinding during replication. We propose the following model for ATP-independent
      DNA unwinding by DBP. Multimerization via the C-terminal arm is required for the
      formation of a protein filament that saturates the displaced strand. A high
      affinity of a DBP monomer for ssDNA and subsequent local destabilization of the
      replication fork requires the flexible loop.

PMID- 9545376
TI  - TAPASIN, DAXX, RGL2, HKE2 and four new genes (BING 1, 3 to 5) form a dense
      cluster at the centromeric end of the MHC.
AB  - TAPASIN, a gene recently shown to be required for antigen presentation through
      MHC class I molecules, is located 180 kbp centromeric of HLA-DP in a region
      linked to several diseases, and associated with altered developmental phenotypes
      in the mouse. We present the genomic analysis of a 70 kbp gene-dense segment
      flanking the TAPASIN locus, including sequence, structure and preliminary
      characterisation of seven additional genes. BING1 is a Zn finger gene containing
      a POZ motif. BING3 is similar to myosin regulatory light chain. BING4 shows
      homologies only to hypothetical yeast and Caenorhabditis elegans proteins. BING5
      is found within an intron of BING4 on the complementary strand, and encodes a
      molecule with no homologies to database proteins. Another three genes were
      identified whose full sequence was not previously known; namely, RGL2, DAXX
      (BING2) and HKE2. RGL2 encodes an effector of Ras, homologous to the mouse RalGDS
      protein, Rlf. DAXX encodes an effector of Fas that stimulates apoptosis through
      the Jun kinase (JNK) pathway. The location of DAXX is of interest given the
      linkage of autoimmune disease to the MHC and to apoptosis.

PMID- 9545377
TI  - Processing of Escherichia coli alkaline phosphatase: role of the primary
      structure of the signal peptide cleavage region.
AB  - A wide range (69) of mutant Escherichia coli alkaline phosphatases with single
      amino acid substitutions at positions from -5 to +1 of the signal peptide were
      obtained for studying protein processing as a function of the primary structure
      of the cleavage region. Amber suppressor mutagenesis, used to create mutant
      proteins, included: (i) introduction of amber mutations into respective positions
      of the phoA gene; and (ii) expression of each mutant phoA allele in E. coli
      strains producing amber suppressor tRNAs specific to Ala, Cys, Gln, Glu, Gly,
      His, Leu, Lys, Phe, Pro, Ser and Tyr. Most amino acid substitutions at positions 
      3 and -1 resulted in a complete block of protein processing. These data give new
      experimental support for the "-3, -1 rule". Only Ala, Gly and Ser at position -1
      allowed protein processing, and Ala provided the highest rate of processing. The
      results revealed the more conservative nature of the amino acids at the -1
      position of signal peptides of Gram-negative bacteria as compared with those of
      eukaryotic organisms. Position -3 was less regular, since not only Ala, Ser and
      Gly, but also Leu and Cys at this position, allowed the processing. Mutations at
      position -4 had an insignificant effect on the processing. Surprisingly,
      efficient processing was provided mainly by large amino acid residues at position
      -2 and by middle-sized residues at position -5, indicating that the processing
      rate is affected by the size of amino acid residues not only at positions -1 and 
      3. Conformation analysis of the cleavage site taken together with the mutation
      and statistical data suggests an extended beta-conformation of the -5 to -1
      region in the signal peptidase binding pocket.

PMID- 9545378
TI  - Effect of cellular level of FliK on flagellar hook and filament assembly in
      Salmonella typhimurium.
AB  - Frameshift mutations in the fliK gene of Salmonella result in abnormal elongation
      of the hook and the failure to assemble filament (polyhook phenotype). Second
      site suppressor mutations restore filament assembly, but the cells often remain
      defective in hook-length control (polyhook-filament phenotype). Where the
      suppressor mutations are intragenic, the second mutation restores the original
      frame, generating a region of frameshifted sequence, but restoring the natural C
      terminus. Some of these frameshifted sequences contain a UGA (opal) termination
      codon. These cells have few flagella and swarm poorly. We suspected that
      readthrough of UGA by tRNATrp might be the reason for the partial function. When
      the UGA codon was changed to the Trp codon UGG, flagellar assembly and function
      were restored to wild-type levels. Conversely, underexpression of the wild-type
      fliK gene, achieved by changing the sole Trp codon in the sequence (Trp271) to
      UGA, decreased both the number of flagella and the ability to swarm. These
      results validate the readthrough hypothesis and indicate that low levels of FliK
      sustain some degree of flagellation and motility. At low levels of FliK, most
      flagella had polyhooks. With increasing amounts, the morphology progressively
      changed to polyhook-filament, and eventually to wild-type hook-filament. When
      FliK was overproduced, the hook length was slightly shorter (46(+/-7) nm) than
      that of the wild-type strain (55(+/-9) nm). FliK levels were measured by
      immunoblotting. Wild-type levels were about 40 to 80 molecules/cell. FliK
      synthesized by UGA readthrough could be detected when overproduced from plasmid
      fliK-W271opal, and the levels indicated a probability of readthrough of 0.002 to
      0.01. This value was used to estimate the cellular level of underexpressed FliK,
      which could partly restore function to a fliK mutant, at about 0.07 to 0.8
      molecule/cell. These results suggest that FliK does not form a large structure in
      the cytoplasm and may function as a regulatory protein for protein export. A
      model for hook-length control is presented that involves feedback from the
      assembly point to the export apparatus.

PMID- 9545379
TI  - Assembly characteristics of flagellar cap protein HAP2 of Salmonella: decamer and
      pentamer in the pH-sensitive equilibrium.
AB  - The cap of the bacterial flagellum is an oligomeric assembly of HAP2 protein
      (also called FliD), tightly attached to the tip of the flagellar filament.
      Flagellar growth does not occur in fliD-deficient mutants because flagellin
      monomers transported through the central channel of the flagellum leak out
      without polymerizing at the distal end. The structure of the cap complex is not
      known yet. An in vitro assembly of HAP2 proteins was found to have a pentagonal
      shape, while its molecular mass corresponded roughly to that of a dodecamer. To
      characterize the structure and assembly behavior of the complex formed in vitro
      in more detail, the stoichiometry of the complex and the association equilibrium
      have been studied. Crosslinking experiments now clearly show that the HAP2
      complex is decameric. The assembly equilibrium is mainly between the monomer and
      decamer with a minor population of intermediate oligomers involved, and is highly
      dependent on the solution pH as well as the salt concentration: the fraction of
      the decamer sharply rises as the pH decreases from 8.5 to 8.0; the physiological
      concentration of salt partially suppresses the decamer formation. A preferential
      crosslinking within a pentameric unit together with a bipolar feature of the
      complex particle observed by electron microscopy suggests that the decamer is a
      bipolar pair of pentamers. Because of the polar nature of the filament cap
      structure, the pentamer is suggested to be the cap complex with its decamer
      forming surface involved in interactions with the filament.

PMID- 9545380
TI  - Stochastic modeling and optimization of phage display.
AB  - Phage display, SELEX and other methods of combinatorial chemistry have become
      very popular means of finding ligands with high affinities to given targets.
      Despite their success, they suffer from numerous sources of error and bias, such
      as very low initial concentrations of species, non-specific binding, and the
      sampling of only a tiny fraction of the library at the end of an experiment. To
      understand the interaction of these errors and to better devise molecular search
      strategies that take the errors into account, I devise and analyze a highly
      detailed model of phage display. The model is specifically designed to study the
      influence of the stochastic nature of each laboratory step. The model includes
      phage multivalency, multiple classes of targets, and solid-phase equilibrium and
      washing, yet it is amenable to analytic results and rapid computer simulation.
      With both analytic and simulation approaches, I: (1) describe the effects of
      target concentration, phage valency, degree of background binding and other
      laboratory parameters on the probabilities of phage binding and of being
      selected; (2) show the effects of an increasing selection stringency strategy and
      how it results in a tradeoff between rapid library enrichment and high
      probability of sampling the best ligands; and (3) show how the number of phage
      sampled for detailed study at the end of a search alters search success. The work
      concludes with several practical suggestions for the control of selection
      stringency.

PMID- 9545381
TI  - Structures of the Erythrina corallodendron lectin and of its complexes with mono-
      and disaccharides.
AB  - The structures of the Erythrina corallodendron lectin (EcorL) and of its
      complexes with galactose, N-acetylgalactosamine, lactose and N-acetyllactosamine
      were determined at a resolution of 1.9 to 1.95 A. The final R-values of the five
      models are in the range 0.169 to 0.181. The unusual, non-canonical, dimer
      interface of EcorL is made of beta-strands from the two monomers, which face one
      another in a "hand-shake" mode. The galactose molecule in the primary binding
      site is bound in an identical way in all four complexes. Features of the
      electrostatic potential of the galactose molecule match those of the potential in
      the combining site, thus probably pointing to the contribution of the
      electrostatic energy to determining the orientation of the ligand. No
      conformational change occurs in the protein upon binding the ligand. Subtle
      variations in the binding mode of the second monosaccharide (glucose in the
      complex with lactose and N-acetylglucosamine in the complex with N
      acetyllactosamine) were observed. The mobility of Gln219 is lower in the
      complexes with the disaccharides than in the complexes with the monosaccharides,
      indicating further recruitment of this residue to ligand binding through more
      extensive hydrogen bonding in the former complexes. Water molecules that have
      been located in the combining sites of the five structures undergo rearrangement
      in response to binding of the different ligands. The new structural information
      is in qualitative agreement with thermodynamic data on the binding to EcorL.

PMID- 9545382
TI  - The changing nature of the protein folding transition state: implications for the
      shape of the free-energy profile for folding.
AB  - According to landscape theory proteins do not fold by localised pathways, but
      find their native conformation by a progressive organisation of an ensemble of
      partly folded structures down a folding funnel. Here, we use kinetics and protein
      engineering to investigate the shape of the free-energy profile for two-state
      folding, which is the macroscopic view of the funnel process for small and
      rapidly folding proteins. Our experiments are based mainly on structural changes
      of the transition state of chymotrypsin inhibitor 2 (CI2) upon destabilisation
      with temperature and GdnHCl. The transition state ensemble of CI2 is a localised
      feature in the free-energy profile that is sharply higher than the other parts of
      the activation barrier. The relatively fixed position of the CI2 transition state
      on the reaction coordinate makes it easy to characterise but contributes also to
      overshadow the rest of the free-energy profile, the shape of which is
      inaccessible for analysis. Results from mutants of CI2 and comparison with other
      two-state proteins, however, point at the possibility that the barrier for
      folding is generally broad and that localised transition states result from minor
      ripples in the free-energy profile. Accordingly, variabilities in the folding
      kinetics may not indicate different folding mechanisms, but could be accounted
      for by various degrees of ruggedness on top of very broad activation barriers for
      folding. The concept is attractive since it summarises a wide range of folding
      data which have previously seemed unrelated. It is also supported by theory.
      Consistent with experiment, broad barriers predict that new transition state
      ensembles are exposed upon extreme destabilisation or radical mutations.

PMID- 9545383
TI  - Topology of the calmodulin-melittin complex.
AB  - The topology of the Ca2+-calmodulin-melittin ternary complex has been
      investigated by a combined strategy which integrates limited proteolysis and
      cross-linking experiments with mass spectrometric methodologies. The rationale
      behind the methods is that the interface regions of two interacting proteins are
      accessible to the solvent in the isolated molecules, whereas they become
      protected following the formation of the complex. Therefore, when limited
      proteolysis experiments are carried out on both the isolated proteins and the
      complex, differential peptide maps are obtained from which the interface regions
      can be inferred. Alternatively, cross-linking reactions performed under strictly
      controlled conditions lead to the identification of spatially closed amino acid
      residues in the complex. Mass spectrometry can be employed in both procedures for
      the definition of the cleavage sites and to identify covalently linked residues.
      Our results show that melittin interacts with calmodulin by adopting a parallel
      orientation, i.e. the N and C-terminal halves of the peptide are anchored to the
      amino and carboxy-terminal domains of the protein, respectively. This orientation
      is inverted with respect to all the peptide substrates examined so far. A model
      of the complex was designed and refined on the basis of the experimental results,
      supporting the above conclusions. This finding reveals a further dimension to the
      already remarkable capability of calmodulin in binding different protein
      substrates, providing this protein with the capability of regulating an even
      larger number of enzymes.

PMID- 9545384
TI  - Influence of cofactor binding and active site occupancy on the conformation of
      the macromolecular substrate exosite of factor VIIa.
AB  - The catalytic activity of the trypsin-like serine protease coagulation factor
      VIIa is allosterically regulated. In this work, we employed monoclonal antibodies
      as probes to analyze conformational changes in the VII protease domain that are
      induced by zymogen activation, cofactor tissue factor (TF) binding, and active
      site occupancy. The epitopes of three monoclonal antibodies were mapped using a
      panel of 57 individual alanine replacement mutants in the protease domain. Two of
      the antibodies had typical "hot spot" epitopes in a basic cluster above the
      active site cleft and antibody binding to these epitopes was not affected by
      zymogen activation, TF binding, or active site occupancy. In contrast, the
      binding kinetics of VII/VIIa to a monoclonal antibody that mapped to an extended
      epitope overlapping with the macromolecular substrate exosite was affected by
      each of the conformational transitions of the VIIa protease domain. The changes
      in antibody affinity are consistent with a transition from zymogen VII to the
      TF.VIIa complex, with free enzyme VIIa as an intermediate that retains some
      zymogen-like features responsible for its low catalytic activity. In contrast,
      active site occupancy resulted in effects that were qualitatively different from
      the effects of zymogen activation on the antibody epitope. This provides novel
      insight into the conformational interdependence between the active site, the
      region for macromolecular substrate recognition, and the cofactor binding exosite
      of this allosterically regulated serine protease.

PMID- 9545385
TI  - Molecular mechanisms for cooperative folding of proteins.
AB  - The folding of single-domain globular proteins exhibits the character of first
      order or two-state thermodynamics. The origin of such high cooperativity in
      relatively small polymer systems is still not well understood. Recently, the
      statistical mechanics of protein folding has been studied extensively with simple
      protein models such as short cubic-lattice chains with contact-based
      interactions. While many valuable insights about protein folding were gained with
      such models, some concerns have also arisen, viz. that they lack the character of
      protein backbones whose interactions would limit the folding patterns of
      proteins. Here, a comparative study of the conventional cubic-lattice chain model
      and a fine-grained more realistic lattice protein model with both backbone and
      side-chain interactions is carried out. It is found that, even though both types
      of models exhibit a cooperative two-state folding transition to the native
      structure with optimized force fields, the character and origin of cooperativity
      of the two models are different. In the simple contact-based model, the free
      energy barrier occurs at the low end of the energy scale, and the cooperativity
      arises from a concerted formation of native contacts among many residues in a
      compact state. In the other more complicated model, the free-energy barrier
      occurs in the intermediate energy region, and the folding cooperativity arises
      from collective orientational arrangements of locally structured units in semi
      open conformational states. On the basis of these results, two limiting molecular
      mechanisms for protein folding emerge, which can be used for analyzing the
      folding process of real proteins.

PMID- 9545386
TI  - Contact order, transition state placement and the refolding rates of single
      domain proteins.
AB  - Theoretical studies have suggested relationships between the size, stability and
      topology of a protein fold and the rate and mechanisms by which it is achieved.
      The recent characterization of the refolding of a number of simple, single domain
      proteins has provided a means of testing these assertions. Our investigations
      have revealed statistically significant correlations between the average sequence
      separation between contacting residues in the native state and the rate and
      transition state placement of folding for a non-homologous set of simple, single
      domain proteins. These indicate that proteins featuring primarily sequence-local
      contacts tend to fold more rapidly and exhibit less compact folding transition
      states than those characterized by more non-local interactions. No significant
      relationship is apparent between protein length and folding rates, but a weak
      correlation is observed between length and the fraction of solvent-exposed
      surface area buried in the transition state. Anticipated strong relationships
      between equilibrium folding free energy and folding kinetics, or between chemical
      denaturant and temperature dependence-derived measures of transition state
      placement, are not apparent. The observed correlations are consistent with a
      model of protein folding in which the size and stability of the polypeptide
      segments organized in the transition state are largely independent of protein
      length, but are related to the topological complexity of the native state. The
      correlation between topological complexity and folding rates may reflect chain
      entropy contributions to the folding barrier.

PMID- 9545387
TI  - A simple method for analyzing microsatellite allele image patterns generated from
      DNA pools and its application to allelic association studies.
AB  - Allelic association studies provide the most powerful method for locating genes
      of small effect contributing to complex diseases and traits. However, in outbred
      populations, allelic association is usually maintained only over distances of <=1
      cM. Therefore, systematic searches over large regions are costly. Here we present
      a method involving DNA pooling that can be used as a rapid preliminary screen for
      allelic association with the most common class of polymorphic markers, single
      sequence repeats. Patient and control samples are pooled separately, and markers
      are typed in the two pools. By use of primers with fluorescent 5' ends, PCR
      products can be analyzed on an automated sequencing apparatus. Allele image
      patterns (AIPs) produced for the two groups are overlaid and differences in
      pattern area between pools computed. From this, a DeltaAIP statistic is
      calculated from the difference in areas between the two AIPs expressed as a
      fraction of the total shared and nonshared area. AIPs of a range of different
      sized pools were generated by computer simulation for markers with a range of
      allele sizes and frequencies. DeltaAIPs from pools and chi2 values for individual
      genotypings were compared, with both simulated and real data from microsatellite
      markers. The results demonstrated a high correlation between DeltaAIP and chi2
      values. DeltaAIP analysis of real microsatellite data indicated the feasibility
      of using this method in systematic searches for allelic association and generated
      a small number of false positives but few false negatives. We conclude that
      DeltaAIP analysis of DNA pools can be used effectively and efficiently as a rapid
      screen for allelic association in case-control studies.

PMID- 9545388
TI  - An analysis of linkage disequilibrium in the interleukin-1 gene cluster, using a
      novel grouping method for multiallelic markers.
AB  - In population- and family-based association studies, it is useful to have some
      knowledge of the patterns of linkage disequilibrium that exist between markers in
      candidate regions. When such studies are carried out with multiallelic markers,
      it is often convenient to group the alleles into a biallelic system, for
      analysis. In this study, we specifically examined the interleukin-1 (IL-1) gene
      cluster on chromosome 2, a region containing candidates for many inflammatory and
      autoimmune disorders. Data were collected on eight markers, four of which were
      multiallelic. Using these data, we investigated the effect of three allele
      grouping strategies, including a novel method, on the detection of linkage
      disequilibrium. The novel approach, termed the "delta method," measures the
      deviation from the expected haplotype frequencies under linkage equilibrium, for
      each allelic combination. This information is then used to group the alleles, in
      an attempt to avoid the grouping together of alleles at one locus that are in
      opposite disequilibrium with the same allele at the second locus. The estimate
      haplotype frequencies (EH) program was used to estimate haplotype frequencies and
      the disequilibrium measure. In our data it was found that the delta method
      compared well with the other two strategies. Using this method, we found that
      there was a reasonable correlation between disequilibrium and physical distance
      in the region (r=-.540, P=.001, one-tailed). We also identified a common, eight
      locus haplotype of the IL-1 gene cluster.

PMID- 9545389
TI  - Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis.
AB  - Autosomal recessive lamellar ichthyosis is a severe congenital disorder of
      keratinization, characterized by variable erythema of the whole body surface and
      by different scaling patterns. Recently, mutations have been identified in
      patients with lamellar ichthyosis in the TGM1 gene coding for keratinocyte
      transglutaminase, and a second locus has been mapped to chromosome 2. We have now
      analyzed the genotype/phenotype correlation in a total of 14 families with
      lamellar ichthyosis. Linkage analyses using microsatellites in the region of the
      TGM1 gene confirmed genetic heterogeneity. In patients not linked to the TGM1
      gene, the second region identified on chromosome 2 and a further candidate region
      on chromosome 20 were excluded, confirming as well the existence of at least
      three loci for lamellar ichthyosis. Sequence analyses of the TGM1 gene in
      families compatible with linkage to this locus revealed seven different missense
      mutations, five of these unpublished so far, and one splice mutation. No
      genotype/phenotype correlation for mutations in the TGM1 gene was found in this
      group of patients, which included two unrelated patients homozygous for the same
      mutation. Similarly, no clear difference in the clinical picture was seen between
      patients with TGM1 mutations and those unlinked to the TGM1 locus. Comparison of
      genetic and clinical classifications for patients with lamellar ichthyosis shows
      no consistency and thus indicates that clinical criteria currently in use cannot
      discriminate between the molecularly different forms of the disease.

PMID- 9545390
TI  - Segregation of a PRKCG mutation in two RP11 families.

PMID- 9545393
TI  - Statistical evaluation of age-at-onset anticipation: a new test and evaluation of
      its behavior in realistic applications.
AB  - The discovery that microsatellite repeat expansions can cause clinical disease
      has fostered renewed interest in testing for age-at-onset anticipation (AOA). A
      commonly used procedure is to sample affected parent-child pairs (APCPs) from
      available data sets and to test for a difference in mean age at onset between the
      parents and the children. However, standard statistical methods fail to take into
      account the right truncation of both the parent and child age-at-onset
      distributions under this design, with the result that type I error rates can be
      inflated substantially. Previously, we had introduced a new test, based on the
      correct, bivariate right-truncated, age-at-onset distribution. We showed that
      this test has the correct type I error rate for random APCPs, even for quite
      small samples. However, in that paper, we did not consider two key statistical
      complications that arise when the test is applied to realistic data. First,
      affected pairs usually are sampled from pedigrees preferentially selected for the
      presence of multiple affected individuals. In this paper, we show that this will
      tend to inflate the type I error rate of the test. Second, we consider the
      appropriate probability model under the alternative hypothesis of true AOA due to
      an expanding microsatellite mechanism, and we show that there is good reason to
      believe that the power to detect AOA may be quite small, even for substantial
      effect sizes. When the type I error rate of the test is high relative to the
      power, interpretation of test results becomes problematic. We conclude that, in
      many applications, AOA tests based on APCPs may not yield meaningful results.

PMID- 9545391
TI  - A syndrome of severe mental retardation, spasticity, and tapetoretinal
      degeneration linked to chromosome 15q24.
AB  - Nine affected individuals are described from a large extended Pakistani family
      manifesting a syndrome characterized by a triad of varying degrees of spasticity,
      severe mental retardation, and visual impairment resulting from tapetoretinal
      degeneration. In all cases, the parents were at least first cousins, since there
      was complex consanguinity within the pedigree. The clinical features differ from
      previously reported syndromes involving pigmentary retinal degeneration and
      appear to represent a new recessively inherited neurodegenerative condition.
      Linkage to a 4-5 cM-region between markers D15S211 and D15S152 on 15q24 has been
      established by autozygosity mapping.

PMID- 9545392
TI  - mtDNA analysis reveals a major late Paleolithic population expansion from
      southwestern to northeastern Europe.
AB  - mtDNA sequence variation was studied in 419 individuals from nine Eurasian
      populations, by high-resolution RFLP analysis, and it was followed by sequencing
      of the control region of a subset of these mtDNAs and a detailed survey of
      previously published data from numerous other European populations. This analysis
      revealed that a major Paleolithic population expansion from the "Atlantic zone"
      (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial
      Maximum. As an mtDNA marker for this expansion we identified haplogroup V, an
      autochthonous European haplogroup, which most likely originated in the northern
      Iberian peninsula or southwestern France at about the time of the Younger Dryas.
      Its sister haplogroup, H, which is distributed throughout the entire range of
      Caucasoid populations and which originated in the Near East approximately 25,000
      30,000 years ago, also took part in this expansion, thus rendering it by far the
      most frequent (40%-60%) haplogroup in western Europe. Subsequent migrations after
      the Younger Dryas eventually carried those "Atlantic" mtDNAs into central and
      northern Europe. This scenario, already implied by archaeological records, is
      given overwhelming support from both the distribution of the autochthonous
      European Y chromosome type 15, as detected by the probes 49a/f, and the synthetic
      maps of nuclear data.

PMID- 9545394
TI  - Autozygosity mapping, to chromosome 11q25, of a rare autosomal recessive syndrome
      causing histiocytosis, joint contractures, and sensorineural deafness.
AB  - We describe a highly consanguineous family, originating from Pakistan, displaying
      histiocytosis, joint contractures, and sensorineural deafness. The form of
      histiocytosis exhibited by this family does not fit readily into any of the
      recognized classes of this disease. It appears to represent a novel form of
      familial histiocytosis demonstrating autosomal recessive inheritance. Using
      autozygosity mapping, we have identified a homozygous region of approximately 1
      cM at chromosome 11q25, in affected individuals. A maximum two-point LOD score of
      3.42 (recombination fraction straight theta = .00) was obtained with marker
      D11S968. This is the first genetic locus to be described that is involved in the
      molecular pathogenesis of histiocytosis.

PMID- 9545395
TI  - A second common mutation in the methylenetetrahydrofolate reductase gene: an
      additional risk factor for neural-tube defects?
AB  - Recently, we showed that homozygosity for the common 677(C-->T) mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the
      enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another
      mutation in the same gene, the 1298(A-->C) mutation, which changes a glutamate
      into an alanine residue. This mutation destroys an MboII recognition site and has
      an allele frequency of .33. This 1298(A-->C) mutation results in decreased MTHFR
      activity (one-way analysis of variance [ANOVA] P < .0001), which is more
      pronounced in the homozygous than heterozygous state. Neither the homozygous nor
      the heterozygous state is associated with higher plasma homocysteine (Hcy) or a
      lower plasma folate concentration-phenomena that are evident with homozygosity
      for the 677(C-->T) mutation. However, there appears to be an interaction between
      these two common mutations. When compared with heterozygosity for either the
      677(C-->T) or 1298(A-->C) mutations, the combined heterozygosity for the 1298(A-
      >C) and 677(C-->T) mutations was associated with reduced MTHFR specific activity
      (ANOVA P < .0001), higher Hcy, and decreased plasma folate levels (ANOVA P <.03).
      Thus, combined heterozygosity for both MTHFR mutations results in similar
      features as observed in homozygotes for the 677(C-->T) mutation. This combined
      heterozygosity was observed in 28% (n =86) of the NTD patients compared with 20%
      (n =403) among controls, resulting in an odds ratio of 2.04 (95% confidence
      interval: .9-4.7). These data suggest that the combined heterozygosity for the
      two MTHFR common mutations accounts for a proportion of folate-related NTDs,
      which is not explained by homozygosity for the 677(C-->T) mutation, and can be an
      additional genetic risk factor for NTDs.

PMID- 9545396
TI  - A susceptibility locus for bipolar affective disorder on chromosome 4q35.
AB  - Bipolar affective disorder (BAD) affects approximately 1% of the population and
      shows strong heritability. To identify potential BAD susceptibility loci, we
      undertook a 15-cM genome screen, using 214 microsatellite markers on the 35 most
      informative individuals of a large, statistically powerful pedigree. Data were
      analyzed by parametric two-point linkage methods under several diagnostic models.
      LOD scores >1.00 were obtained for 21 markers, with four of these >2.00 for at
      least one model. The remaining 52 individuals in the family were genotyped with
      these four markers, and LOD scores remained positive for three markers. A more
      intensive screen was undertaken in these regions, with the most positive results
      being obtained for chromosome 4q35. Using a dominant model of inheritance with
      90% maximum age-specific penetrance and including bipolar I, II,
      schizoaffective/mania, and unipolar individuals as affected, we obtained a
      maximum two-point LOD score of 2.20 (theta = .15) at D4S1652 and a maximum three
      point LOD score of 3.19 between D4S408 and D4S2924. Nonparametric analyses
      further supported the presence of a locus on chromosome 4q35. A maximum score of
      2.62 (P=.01) was obtained between D4S1652 and D4S171 by use of the GENEHUNTER
      program, and a maximum score of 3.57 (P=.0002) was obtained at D4S2924 using the
      affected pedigree member method. Analysis of a further 10 pedigrees suggests the
      presence of this locus in at least one additional family, indicating a possible
      predisposing locus and not a pedigree-specific mutation. Our results suggest the
      presence of a novel BAD susceptibility locus on chromosome 4q35.

PMID- 9545399
TI  - Mutational mechanisms for generating microsatellite allele-frequency
      distributions: an analysis of 4,558 markers.

PMID- 9545397
TI  - Human meiotic recombination products revealed by sequencing a hotspot for
      homologous strand exchange in multiple HNPP deletion patients.
AB  - The HNPP (hereditary neuropathy with liability to pressure palsies) deletion and
      CMT1A (Charcot-Marie-Tooth disease type 1A) duplication are the reciprocal
      products of homologous recombination events between misaligned flanking CMT1A-REP
      repeats on chromosome 17p11. 2-p12. A 1.7-kb hotspot for homologous recombination
      was previously identified wherein the relative risk of an exchange event is 50
      times higher than in the surrounding 98.7% identical sequence shared by the CMT1A
      REPs. To refine the region of exchange further, we designed a PCR strategy to
      amplify the recombinant CMT1A-REP from HNPP patients as well as the proximal and
      distal CMT1A-REPs from control individuals. By comparing the sequences across
      recombinant CMT1A-REPs to that of the proximal and distal CMT1A-REPs, the
      exchange was mapped to a 557-bp region within the previously identified 1.7-kb
      hotspot in 21 of 23 unrelated HNPP deletion patients. Two patients had recombined
      sequences suggesting an exchange event closer to the mariner-like element
      previously identified near the hotspot. Five individuals also had interspersed
      patches of proximal or distal repeat specific DNA sequence indicating potential
      gene conversion during the exchange of genetic material. Our studies provide a
      direct observation of human meiotic recombination products. These results are
      consistent with the hypothesis that minimum efficient processing segments, which
      have been characterized in Escherichia coli, yeast, and cultured mammalian cells,
      may be required for efficient homologous meiotic recombination in humans.

PMID- 9545398
TI  - Mutations in btk in patients with presumed X-linked agammaglobulinemia.
AB  - In 1993, two groups showed that X-linked agammaglobulinemia (XLA) was due to
      mutations in a tyrosine kinase now called Btk. Most laboratories have been able
      to detect mutations in Btk in 80%-90% of males with presumed XLA. The remaining
      patients may have mutations in Btk that are difficult to identify, or they may
      have defects that are phenotypically similar to XLA but genotypically different.
      We analyzed 101 families in which affected males were diagnosed as having XLA.
      Mutations in Btk were identified in 38 of 40 families with more than one affected
      family member and in 56 of 61 families with sporadic disease. Excluding the
      patients in whom the marked decrease in B cell numbers characteristic of XLA
      could not be confirmed by immunofluorescence studies, mutations in Btk were
      identified in 43 of 46 patients with presumed sporadic XLA. Two of the three
      remaining patients had defects in other genes required for normal B cell
      development, and the third patient was unlikely to have XLA, on the basis of
      results of extensive Btk analysis. Our techniques were unable to identify a
      mutation in Btk in one male with both a family history and laboratory findings
      suggestive of XLA. DNA samples from 41 of 49 of the mothers of males with
      sporadic disease and proven mutations in Btk were positive for the mutation found
      in their son. In the other 8 families, the mutation appeared to arise in the
      maternal germ line. In 20 families, haplotype analysis showed that the new
      mutation originated in the maternal grandfather or great-grandfather. These
      studies indicate that 90%-95% of males with presumed XLA have mutations in Btk.
      The other patients are likely to have defects in other genes.

PMID- 9545400
TI  - Some underlooked properties of the multifactorial/threshold model.

PMID- 9545401
TI  - Dual origins of Finns revealed by Y chromosome haplotype variation.
AB  - The Finnish population has often been viewed as an isolate founded 2, 000 years
      ago via a route across the Gulf of Finland. The founding event has been
      characterized as involving a limited number of homogeneous founders, isolation,
      and subsequent rapid population growth. Despite the purported isolation of the
      population, levels of gene diversity for the Finns at autosomal and mitochondrial
      DNA loci are indistinguishable from those of other Europeans. Thus, mixed or dual
      origins for the Finns have been proposed. Here we present genetic evidence for
      the dual origins of Finns by evaluating the pattern of Y chromosome variation in
      280 unrelated males from nine Finnish provinces. Phylogenetic analysis of 77
      haplotype configurations revealed two major star-shaped clusters of Y haplotypes,
      indicative of a population expansion from two common Y haplotypes. Dramatic and
      quite significant differences in Y haplotype variation were observed between
      eastern and western regions of Finland, revealing contributions from different
      paternal types. The geographic distribution and time of expansion for the two
      common Y haplotypes correlate well with archeological evidence for two culturally
      and geographically distinct groups of settlers. Also, a northeastern to
      southwestern gradient of Y haplotype frequencies provides convincing evidence for
      recent male migration from rural areas into urban Finland.

PMID- 9545402
TI  - Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.
AB  - Autistic disorder is a complex genetic disease. Because of previous reports of
      individuals with autistic disorder with duplications of the Prader-Willi/Angelman
      syndrome critical region, we screened several markers across the 15q11-13 region,
      for linkage disequilibrium. One hundred forty families, consisting predominantly
      of a child with autistic disorder and both parents, were studied. Genotyping was
      performed by use of multiplex PCR and capillary electrophoresis. Two children
      were identified who had interstitial chromosome 15 duplications and were excluded
      from further linkage-disequilibrium analysis. Use of the multiallelic
      transmission-disequilibrium test (MTDT), for nine loci on 15q11-13, revealed
      linkage disequilibrium between autistic disorder and a marker in the gamma
      aminobutyric acidA receptor subunit gene, GABRB3 155CA-2 (MTDT 28.63, 10 df,
      P=.0014). No evidence was found for parent-of-origin effects on allelic
      transmission. The convergence of GABRB3 as a positional and functional candidate
      along with the linkage-disequilibrium data suggests the need for further
      investigation of the role of GABRB3 or adjacent genes in autistic disorder.

PMID- 9545403
TI  - Linkage disequilibrium analysis in a recently founded population: evaluation of
      the variegate porphyria founder in South African Afrikaners.

PMID- 9545404
TI  - Localization of the gene for congenital dyserythropoietic anemia type I to a <1
      cM interval on chromosome 15q15.1-15.3.
AB  - Congenital dyserythropoietic anemias (CDA) are a rare group of red-blood-cell
      disorders of unknown etiology that are characterized by ineffective
      erythropoiesis, pathognomonic cytopathology of the nucleated red blood cells in
      the bone marrow, and secondary hemochromatosis. In CDA type I, bone-marrow
      electron microscopy reveals characteristic findings in erythroid precursors,
      including spongy heterochromatin and enlarged nuclear pores. Since the genetic
      basis of CDA type I is not evident, we used homozygosity and linkage mapping to
      localize the genetic defect responsible for CDA type I in 25 Bedouins from four
      large consanguineous families. We report the linkage of this disease to markers
      on chromosome 15 located at q15. 1-q15.3. Fourteen markers within a 12-cM
      interval were typed in the relevant family members. Nine of the markers yielded
      maximum LOD scores of 1.625-12.928 at a recombination fraction of .00. Linkage
      disequilibrium was found only with marker D15S779. Haplotype analysis revealed
      eight different carrier haplotypes and highlighted the existence of a founder
      haplotype. Identification of historical crossover events further narrowed the
      gene location to between D15S779 and D15S778. The data suggest localization of
      the CDA type I gene within a 0.5-cM interval. The founder mutation probably
      occurred >/= 400 years ago. Sequence analysis of the coding region of protein
      4.2, the only known erythroid-specific gene in the locus, did not reveal any
      change in the CDA type I patients. Future analysis of this locus may lead to the
      identification of a gene essential to normal erythropoiesis.

PMID- 9545406
TI  - Worldwide distribution of a common methylenetetrahydrofolate reductase mutation.

PMID- 9545405
TI  - Renpenning syndrome maps to Xp11.
AB  - Mutations in genes on the X chromosome are believed to be responsible for the
      excess of males among individuals with mental retardation. Such genes are
      numerous, certainly >100, and cause both syndromal and nonsyndromal types of
      mental retardation. Clinical and molecular studies have been conducted on the
      Mennonite family with X-linked mental retardation (XLMR) reported, in 1962, by
      Renpenning et al. The clinical phenotype includes severe mental retardation,
      microcephaly, up-slanting palpebral fissures, small testes, and stature shorter
      than that of nonaffected males. Major malformations, neuromuscular abnormalities,
      and behavioral disturbances were not seen. Longevity is not impaired. Carrier
      females do not show heterozygote manifestations. The syndrome maps to Xp11.2
      p11.4, with a maximum LOD score of 3.21 (recombination fraction 0) for markers
      between DXS1039 and DXS1068. Renpenning syndrome (also known as "MRXS8"; gene
      RENS1, MIM 309500) shares phenotypic manifestations with several other XLMR
      syndromes, notably the Sutherland-Haan syndrome. In none of these entities has
      the responsible gene been isolated; hence, the possibility that two or more of
      them may be allelic cannot be excluded at present.

PMID- 9545407
TI  - The Bjornstad syndrome (sensorineural hearing loss and pili torti) disease gene
      maps to chromosome 2q34-36.
AB  - We report that the Bjornstad syndrome gene maps to chromosome 2q34-36. The
      clinical association of sensorineural hearing loss with pili torti (broken,
      twisted hairs) was described >30 years ago by Bjornstad; subsequently, several
      small families have been studied. We evaluated a large kindred with Bjornstad
      syndrome in which eight members inherited pili torti and prelingual sensorineural
      hearing loss as autosomal recessive traits. A genomewide search using polymorphic
      loci demonstrated linkage between the disease gene segregating in this kindred
      and D2S434 (maximum two-point LOD score = 4.98 at theta = 0). Haplotype analysis
      of recombination events located the disease gene in a 3-cM region between loci
      D2S1371 and D2S163. We speculate that intermediate filament and intermediate
      filament-associated proteins are good candidate genes for causing Bjornstad
      syndrome.

PMID- 9545409
TI  - A gene for autosomal dominant hypohidrotic ectodermal dysplasia (EDA3) maps to
      chromosome 2q11-q13.
AB  - Autosomal dominant hypohidrotic ectodermal dysplasia (ADHED) is a disorder
      characterized by fine, slow-growing scalp and body hair, sparse eyebrows and
      eyelashes, decreased sweating, hypodontia, and nail anomalies. By genetic linkage
      analysis of a large ADHED kindred, we have mapped a gene for ADHED (EDA3) to the
      proximal long arm of chromosome 2 (q11-q13). Obligate recombinations localize
      EDA3 to an approximately 9-cM interval between D2S1321 and D2S308, with no
      apparent recombinations with markers D2S1343, D2S436, D2S293, D2S1894, D2S1784,
      D2S1890, D2S274, and CHLC.GAAT11C03.

PMID- 9545408
TI  - mtDNA analysis of a prehistoric Oneota population: implications for the peopling
      of the New World.
AB  - mtDNA was successfully extracted from 108 individuals from the Norris Farms
      Oneota, a prehistoric Native American population, to compare the mtDNA diversity
      from a pre-Columbian population with contemporary Native American and Asian mtDNA
      lineages and to examine hypotheses about the peopling of the New World.
      Haplogroup and hypervariable region I sequence data indicate that the lineages
      from haplogroups A, B, C, and D are the most common among Native Americans but
      that they were not the only lineages brought into the New World from Asia. The
      mtDNA evidence does not support the three-wave hypothesis of migration into the
      New World but rather suggests a single "wave" of people with considerable mtDNA
      diversity that exhibits a signature of expansion 23,000-37,000 years ago.

PMID- 9545411
TI  - Mapping of a congenital microcoria locus to 13q31-q32.
AB  - Congenital microcoria is an autosomal dominant disorder characterized by a pupil
      with a diameter <2 mm. It is thought to be due to a maldevelopment of the dilator
      pupillae muscle of the iris, and it is associated with juvenile-onset glaucoma. A
      total genome search for the location of the congenital microcoria gene was
      launched in a single large family. We found linkage between the disease and
      markers located on 13q31-q32 (Zmax = 9.79; theta = 0). Haplotype analysis
      narrowed the linked region to an interval <8 cM between markers D13S1239
      proximally and D13S1280 distally.

PMID- 9545410
TI  - A gene for familial juvenile polyposis maps to chromosome 18q21.1.
AB  - Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which
      affected family members develop upper and lower gastrointestinal juvenile polyps
      and are at increased risk for gastrointestinal cancer. A genetic locus for FJP
      has not yet been identified by linkage; therefore, the objective of this study
      was to perform a focused genome screen in a large family segregating FJP. No
      evidence for linkage was found with markers near MSH2, MLH1, MCC, APC, HMPS,
      CDKN2A, JP1, PTEN, KRAS2, TP53, or LKB1. Linkage to FJP was established with
      several markers from chromosome 18q21.1. The maximum LOD score was 5.00, with
      marker D18S1099 (recombination fraction of .001). Analysis of critical
      recombinants places the FJP gene in an 11.9-cM interval bounded by D18S1118 and
      D18S487, a region that also contains the tumor-suppressor genes DCC and DPC4.
      These data demonstrate localization of a gene for FJP to chromosome 18q21.1 by
      linkage, and they raise the possibility that either DCC or DPC4 could be
      responsible for FJP.

PMID- 9545412
TI  - Diversity of cystic fibrosis mutation-screening practices.

PMID- 9545413
TI  - A locus for autosomal recessive congenital microphthalmia maps to chromosome
      14q32.
AB  - Congenital microphthalmia (CMIC) (OMIM 309700) may occur in isolation or in
      association with a variety of systemic malformations. Isolated CMIC may be
      inherited as an autosomal dominant, an autosomal recessive, or an X-linked trait.
      On the basis of a whole-genome linkage analysis, we have mapped the first locus
      for isolated CMIC, in a five-generation consanguineous family with autosomal
      recessive inheritance, to chromosome 14q32. All affected individuals in this
      family have bilateral CMIC. Linkage analysis gave a maximum two-point LOD score
      of 3.55 for the marker D14S65. Surrounding this marker is a region of
      homozygosity of 7.3 cM, between the markers D14S987 and D14S267, within which the
      disease gene is predicted to lie. The genes for several eye-specific
      transcription factors are located on human chromosome 14q and in the syntenic
      region of mouse chromosome 12. However, both CHX10 (14q24.3), mutations of which
      give rise to CMIC in mouse models, and OTX2 (14q21-22) can be excluded as
      candidates for autosomal recessive congenital microphthalmia (arCMIC), since they
      map outside the critical disease region defined by recombination events. This
      suggests that arCMIC is caused by defects in a novel developmental gene that may
      be important or even essential in eye development.

PMID- 9545414
TI  - Multipoint quantitative-trait linkage analysis in general pedigrees.
AB  - Multipoint linkage analysis of quantitative-trait loci (QTLs) has previously been
      restricted to sibships and small pedigrees. In this article, we show how variance
      component linkage methods can be used in pedigrees of arbitrary size and
      complexity, and we develop a general framework for multipoint identity-by-descent
      (IBD) probability calculations. We extend the sib-pair multipoint mapping
      approach of Fulker et al. to general relative pairs. This multipoint IBD method
      uses the proportion of alleles shared identical by descent at genotyped loci to
      estimate IBD sharing at arbitrary points along a chromosome for each relative
      pair. We have derived correlations in IBD sharing as a function of chromosomal
      distance for relative pairs in general pedigrees and provide a simple framework
      whereby these correlations can be easily obtained for any relative pair related
      by a single line of descent or by multiple independent lines of descent. Once
      calculated, the multipoint relative-pair IBDs can be utilized in variance
      component linkage analysis, which considers the likelihood of the entire pedigree
      jointly. Examples are given that use simulated data, demonstrating both the
      accuracy of QTL localization and the increase in power provided by multipoint
      analysis with 5-, 10-, and 20-cM marker maps. The general pedigree variance
      component and IBD estimation methods have been implemented in the SOLAR
      (Sequential Oligogenic Linkage Analysis Routines) computer package.

PMID- 9545415
TI  - Replicative senescence in the immune system: impact of the Hayflick limit on T
      cell function in the elderly.

PMID- 9545416
TI  - ACMG/ASHG statement. Laboratory guidelines for Huntington disease genetic
      testing. The American College of Medical Genetics/American Society of Human
      Genetics Huntington Disease Genetic Testing Working Group.

PMID- 9545417
TI  - Molecular classification of the inherited hamartoma polyposis syndromes: clearing
      the muddied waters.

PMID- 9545418
TI  - The genetics of cellular senescence.

PMID- 9545420
TI  - Pharmaceutical biotechnology.

PMID- 9545421
TI  - Cytoskeleton.

PMID- 9545419
TI  - Causes, effects, and constraints in the genetics of human longevity.

PMID- 9545422
TI  - Cytoskeleton.

PMID- 9545423
TI  - Solution structure of a synthetic lytic peptide: the perforin amino terminus.
AB  - BACKGROUND: Killer lymphocytes secrete perforin, a 67 kDa protein that initiates
      T-cell cytolysis following aggregation and pore formation in target membranes.
      The resulting pores cause a breakdown of the transmembrane osmotic gradient and
      allow other cytolytic mediators to enter the target cell and initiate apoptosis.
      The cytolytic domain resides within the first 34 residues of the amino terminus
      of perforin, with residues 1-19 being sufficient for cytolytic activity. RESULTS:
      The solution structure of a 22-residue synthetic peptide (P22), corresponding to
      the amino terminus of human perforin, has been determined using high resolution
      nuclear magnetic resonance spectroscopy in the presence and absence of
      perdeuterated detergent (SDS) micelles. In aqueous solution, P22 exists mainly in
      a random conformation. However, it adopts a hook-like structure at the carboxyl
      terminus in the presence of SDS micelles when the positively charged residues
      cluster to form a turn that provides a binding surface to the negatively charged
      sulfate headgroups. CONCLUSIONS: The strong electrostatic interaction between the
      cationic region of the P22 peptide and the lipid headgroups probably weakens the
      membrane, facilitating insertion of the relatively neutral/hydrophobic stretch of
      P22, and is representative of the initial step of the lytic pathway. The
      structural model described here is probably relevant to understanding the
      mechanisms of other cationic antimicrobial peptides.

PMID- 9545424
TI  - Heterologously expressed acyl carrier protein domain of rat fatty acid synthase
      functions in Escherichia coli fatty acid synthase and Streptomyces coelicolor
      polyketide synthase systems.
AB  - INTRODUCTION: Fatty acid synthases (FASs) catalyze the de novo biosynthesis of
      long-chain saturated fatty acids by a process common to eubacteria and
      eukaryotes, using either a set of monofunctional proteins (Type II FAS) or a
      polypeptide containing several catalytic functions (Type I FAS). To compare the
      features of a Type I domain with its Type II counterpart we expressed and
      characterized an acyl carrier protein (ACP) domain of the Type I rat FAS.
      RESULTS: An ACP domain of rat FAS was defined that allows expression of a small
      percentage of active holo-ACP both in Escherichia coli, increasing fivefold upon
      co-expression with an E. coli holo-ACP synthase, and in Streptomyces coelicolor.
      The rat ACP domain functions with some components of the E. coli FAS, and can
      replace the actinorhodin polyketide synthase (PKS) ACP in S. coelicolorA3(2).
      Purification of the rat ACP domain from E. coli resulted in loss of its
      functionality. Purified apo-ACP could be converted to its holo-form upon
      incubation with purified E. coli holo-ACP synthase in vitro, however, suggesting
      that the loss of functionality was not due to a conformational change.
      CONCLUSIONS: Functionality of the recombinant rat ACP was shown in distantly
      related and diverse enzyme systems, suggesting that Type I and Type II ACPs have
      a similar conformation. A procedure was described that might permit the
      production of rat FAS holo-ACP for structural and further biochemical
      characterization.

PMID- 9545425
TI  - Visualizing metal-ion-binding sites in group I introns by iron(II)-mediated
      Fenton reactions.
AB  - BACKGROUND: Most catalytic RNAs depend on divalent metal ions for folding and
      catalysis. A thorough structure-function analysis of catalytic RNA therefore
      requires the identification of the metal-ion-binding sites. Here, we probed the
      binding sites using Fenton chemistry, which makes use of the ability of Fe2+ to
      functionally or structurally replace Mg2+ at ion-binding sites and to generate
      short-lived and highly reactive hydroxyl radicals that can cleave nucleic acid
      and protein backbones in spatial proximity of these ion-binding sites. RESULTS:
      Incubation of group I intron RNA with Fe2+, sodium ascorbate and hydrogen
      peroxide yields distinctly cleaved regions that occur only in the correctly
      folded RNA in the presence of Mg2+ and can be competed by additional Mg2+,
      suggesting that Fe2+ and Mg2+ interact with the same sites. Cleaved regions in
      the catalytic core are conserved for three different group I introns, and there
      is good correlation between metal-ion-binding sites determined using our method
      and those determined using other techniques. In a model of the T4 phage-derived
      td intron, cleaved regions separated in the secondary structure come together in
      three-dimensional space to form several metal-ion-binding pockets. CONCLUSIONS:
      In contrast to structural probing with Fe2+/EDTA, cleavage with Fe2+ detects
      metal-ion-binding sites located primarily in the inside of the RNA. Essentially
      all metal-ion-binding pockets detected are formed by tertiary structure elements.
      Using this method, we confirmed proposed metal-ion-binding sites and identified
      new ones in group I intron RNAs. This approach should allow the localization of
      metal-ion-binding sites in RNAs of interest.

PMID- 9545426
TI  - Sequencing and analysis of genes involved in the biosynthesis of a vancomycin
      group antibiotic.
AB  - BACKGROUND: The emergence of resistance to vancomycin, the drug of choice against
      methicillin-resistant Staphylococcus aureus, in enterococci has increased the
      need for new antibiotics. As chemical modification of the antibiotic structure is
      not trivial, we have initiated studies towards enzymatic modification by
      sequencing the DNA coding for the biosynthesis of chloroeremomycin (also known as
      A82846B and LY264826). RESULTS: Analysis of 72 kilobases of genomic DNA from
      Amycolatopsis orientalis, the organism that produces chloroeremomycin, revealed
      the presence of 39 putative genes, including those coding for the biosynthesis of
      the antibiotic. Translation and subsequent comparison with known proteins in
      public databases identified enzymes responsible for the biosynthesis of the
      heptapeptide backbone and 4-epi-vancosamine, as well as those for chlorination
      and oxidation reactions involved in the biosynthesis of chloroeremomycin.
      CONCLUSIONS: The genes responsible for the biosynthesis of chloroeremomycin have
      been identified, and selective expression of these genes could lead to the
      synthesis of new potent glycopeptide antibiotics.

PMID- 9545427
TI  - Transforming the cell surface through proteolysis.
AB  - Protein shedding, or the proteolytic cleavage of a protein from the surface of a
      cell, is emerging as an important mechanism in the regulation of cellular
      activity but it is poorly understood. Growing evidence suggesting that protein
      shedding and protein function are closely linked may lead to new strategies for
      the treatment of a wide range of diseases.

PMID- 9545428
TI  - Self-assembly and steric stabilization at heterogeneous, biological surfaces
      using adsorbing block copolymers.
AB  - BACKGROUND: We present the synthesis, characterization and initial structure
      function analysis of a new class of bioactive agent that allows the application
      of techniques from colloid science to biological surfaces. Stable colloidal
      suspensions can be generated by immobilizing a dense brush of soluble polymer at
      the colloidal surface, creating a zone protected against the adhesion of
      approaching particles, a phenomenon termed polymeric steric stabilization. This
      is often accomplished for aqueous colloidal dispersions using adsorbing block
      copolymers. We demonstrate that water-soluble block copolymers can be designed to
      adsorb onto heterogeneous biological surfaces and block cell-cell and cell
      surface adhesion, using polymer compositions and architectures that are quite
      different from surfactants used for stabilizing nonbiological colloidal
      dispersions. RESULTS: Comb copolymers were synthesized having polycationic
      backbones (poly-L-lysine, PLL), serving as the anchor for binding to the net
      negatively charged biological surfaces, grafted with water-soluble polynonionic
      chains (polyethylene glycol, PEG), to block biological recognition, producing PLL
      graft-PEG copolymers. Specific copolymers were found to sterically stabilize red
      blood cells from lectin-induced hemagglutination and fibroblasts from adhesion to
      fibronectin-coated surfaces. The polymer design principles, which appear to be
      unique for adsorption to heterogeneous biological surfaces, require the use of
      very high molecular weight comb copolymers, perhaps because anionic sites are non
      uniformly distributed on biological surfaces, and the ability of larger
      copolymers to span between highly anionic sites. CONCLUSIONS: Water-soluble
      copolymers were produced that can block recognition at biological surfaces, on
      the basis of nonspecific physicochemical phenomena rather than specific
      biochemical interactions.

PMID- 9545429
TI  - Inhibition of major-groove-binding proteins by pyrrole-imidazole polyamides with
      an Arg-Pro-Arg positive patch.
AB  - BACKGROUND: Gene-specific targeting of any protein-DNA complex by small molecules
      is a challenging goal at the interface of chemistry and biology. Polyamides
      containing N-methylimidazole and N-methylpyrrole amino acids are synthetic
      ligands that have an affinity and specificity for DNA comparable to many
      naturally occurring DNA-binding proteins. It has been shown that an eight-ring
      hairpin polyamide targeted to a specific minor-groove contact within a
      transcription factor binding site can inhibit protein-DNA binding and gene
      transcription. Polyamides and certain major-groove-binding proteins have been
      found to co-occupy the DNA helix, however. To expand the number of genes that can
      be targeted by pyrrole/imidazole polyamides, we set out to develop a class of
      polyamides that can selectively inhibit major-groove-binding proteins. RESULTS:
      An eight-ring hairpin polyamide conjugated to a carboxy-terminal Arg-Pro-Arg
      tripeptide was designed to deliver a positive residue to the DNA backbone and
      interfere with protein-phosphate contacts. Gel mobility shift analysis
      demonstrated that a polyamide hairpin-Arg-Pro-Arg binding in the minor groove
      selectively inhibits binding of the transcription factor GCN4 (222-281) in the
      adjacent major groove. Substitution within the Arg-Pro-Arg revealed that each
      residue was required for optimal GCN4 inhibition. CONCLUSIONS: A pyrrole
      imidazole polyamide that binds to a predetermined site in the DNA minor groove
      and delivers a positive patch to the DNA backbone can selectively inhibit a DNA
      binding protein that recognizes the adjacent major groove. A subtle alteration of
      the DNA microenvironment targeted to a precise location within a specific DNA
      sequence could achieve both gene-specific and protein-specific targeting.

PMID- 9545430
TI  - Rainforest remedies Shaman Pharmaceuticals, Inc

PMID- 9545431
TI  - Active-site mutants of the VanC2 D-alanyl-D-serine ligase, characteristic of one
      vancomycin-resistant bacterial phenotype, revert towards wild-type D-alanyl-D
      alanine ligases.
AB  - BACKGROUND: The rising number of vancomycin-resistant enterococci (VREs) is a
      major concern to modern medicine because vancomycin is currently the 'last
      resort' drug for life-threatening infections. The D-alanyl-D-X ligases (where X
      is an hydroxy or amino acid) of bacteria catalyze a critical step in bacterial
      cell-wall peptidoglycan assembly. In bacteria that produce glycopeptide
      antibiotics and in opportunistic pathogens, including VREs, D-, D-ligases serve
      as switches that confer antibiotic resistance on the bacteria themselves.
      Peptidoglycans in vancomycin-sensitive bacteria end in D-alanyl-D-alanine,
      whereas in vancomycin-resistant bacteria they end in D-alanyl-D-lactate or D
      alanyl-D-serine. RESULTS: We demonstrate that the selective utilization of D
      serine by the Enterococcus casseliflavus VanC2 ligase can be altered by
      mutagenesis of one of two residues identified by homology to the X-ray structure
      of the Escherichia coli D-alanyl-Dalanine ligase (DdlB). The Arg322-->Met (R322M)
      and Phe250-->Tyr (F250Y) ligase mutants show a 36-44-fold decrease in the use of
      D-serine, as well as broadened specificity for utilization of other D-amino acids
      in place of D-serine. The F250Y R322M double mutant is effectively disabled as a
      D-alanyl-D-serine ligase and retains 10% of the catalytic activity of wild-type D
      alanyl-D-alanine ligases, reflecting a 6,000-fold switch to the D-alanyl-D
      alanine peptide. Correspondingly, the Leu282-->Arg mutant of the wild-type E.
      coli DdlB produced a 560-fold switch towards D-alanyl-D-serine formation.
      CONCLUSIONS: Single-residue changes in the active-site regions of D-, D-ligases
      can cause substantial changes in recognition and activation of hydroxy or amino
      acids that have consequences for glycopeptide antibiotic efficacy. The
      observations reported here should provide an approach for combatting antibiotic
      resistant bacteria.

PMID- 9545433
TI  - Analysis of the conversion of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha
      aminobutyrate by active-site mutants of Aspergillus nidulans isopenicillin N
      synthase.
AB  - BACKGROUND: Penicillins and cephalosporins constitute a major class of clinically
      useful antibiotics. A key step in their biosynthesis involves the oxidative
      cyclisation of delta-(Lalpha-aminoadipoyl)-L-cysteinyl-D-valine to isopenicillin
      N by isopenicillin N synthase (IPNS). This chemically remarkable transformation
      has been extensively studied using substrate analogues. The conversion of an
      analogue in which the valine is replaced by alpha-aminobutyrate results in three
      products, two epimeric penams and a cepham. The ratio of these products in
      reactions catalysed by four different IPNS isozymes has been used previously to
      probe the thermicity of the chemical mechanism. But how IPNS restricts the
      products from the natural substrate to a single penam (isopenicillin N) has
      remained unknown. RESULTS: A key active-site residue, Leu223, identified
      according to a model of enzyme-substrate binding, has been altered to sterically
      less demanding residues. As the steric constraints on the upper part of the
      active site are reduced, the ratio of the beta-methyl penam to the cepham
      increases when the alpha-aminobutyrate-containing substrate analogue is used.
      These results suggest a mechanism for processing of the natural substrate in
      which IPNS uses steric control to restrict the conformational freedom of an
      intermediate such that the only product is the penam. CONCLUSIONS: Using steric
      pressure to control conformation, and hence to disfavour reactions leading to
      alternate products, is probably the result of evolutionary selection for a
      biologically active product at the expense of biologically inactive byproducts.
      It is likely that this sort of enzymatic catalysis is used in situations where
      substrate conversion is highly exothermic and a variety of products are possible.

PMID- 9545432
TI  - Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of
      Bacteroides fragilis metallo-beta-lactamase.
AB  - BACKGROUND: High level resistance to carbapenem antibiotics in gram negative
      bacteria such as Bacteroides fragilis is caused, in part, by expression of a wide
      spectrum metallo-beta-lactamase that hydrolyzes the drug to an inactive form. Co
      administration of metallo-beta-lactamase inhibitors to resistant bacteria is
      expected to restore the antibacterial activity of carbapenems. RESULTS: Biphenyl
      tetrazoles (BPTs) are a structural class of potent competitive inhibitors of
      metallo-beta-lactamase identified through screening and predicted using molecular
      modeling of the enzyme structure. The X-ray crystal structure of the enzyme bound
      to the BPT L-159,061 shows that the tetrazole moiety of the inhibitor interacts
      directly with one of the two zinc atoms in the active site, replacing a metal
      bound water molecule. Inhibition of metallo-beta-lactamase by BPTs in vitro
      correlates well with antibiotic sensitization of resistant B. fragilis.
      CONCLUSIONS: BPT inhibitors can sensitize a resistant B. fragilis clinical
      isolate expressing metallo-beta-lactamase to the antibiotics imipenem or
      penicillin G but not to rifampicin.

PMID- 9545434
TI  - Bicyclo[3.2.1]-DNA, a new DNA analog with a rigid backbone and flexibly linked
      bases: pairing properties with complementary DNA.
AB  - BACKGROUND: The structural and conformational variety in nucleic acid complexes
      is largely controlled by the sugar-phosphate backbone. In order to modulate
      specific features such as strength or selectivity of complex formation by
      designing nucleotide analogs, a deeper understanding of the relationship between
      mononucleotide structures and the properties of their oligomers is necessary. One
      approach involves comparing the properties of DNA analogs displaying well defined
      modifications in their backbone structure with those of natural DNA and RNA.
      RESULTS: We have designed and synthesized a new DNA analog, 'bicyclo[3.2.1]-DNA',
      which has a rigid phosphodiester backbone that emulates a B-DNA-type
      conformation, to which the nucleobases are attached via a flexible open-chain
      linker. A UV-melting curve analysis shows that bicyclo[3.2.1]-DNA forms stable
      duplexes with complementary DNA, although generally with lower Tm values than
      pure DNA duplexes. Duplex formation is strictly constrained to antiparallel
      complementary sequences, and base-mismatch discrimination is slightly enhanced
      compared to pure DNA duplexes. In addition, bicyclo[3.2.1]-DNA sequences are
      resistant to a 3'-exonuclease. CONCLUSIONS: The furanose unit present in natural
      nucleosides is not necessary for a competent and stable phosphodiester-based
      pairing system, provided that the backbone is conformationally constrained. The
      information for the preference of antiparallel strand association in B-DNA is not
      merely a consequence of bases being attached to a specific side of the furanose
      unit, but is also encoded in the backbone itself. Furthermore, conformational
      flexibility in the base-pairing region does not lead to a loss of selectivity in
      base-pair formation.

PMID- 9545436
TI  - Atopic allergy and other hypersensitivities.

PMID- 9545435
TI  - Role of the microcin B17 propeptide in substrate recognition: solution structure
      and mutational analysis of McbA1-26.
AB  - BACKGROUND: The peptide antibiotic microcin B17 (MccB17) contains oxazole and
      thiazole heterocycles formed by the post-translational modification of four
      cysteine and four serine residues. An amino-terminal propeptide targets the 69
      amino acid precursor of MccB17 (preproMccB17) to the heterocyclization enzyme
      MccB17 synthetase. The mode of synthetase recognition has been unclear, because
      there has been limited structural information available on the MccB17 propeptide
      to date. RESULTS: The solution structure of the MccB17 propeptide (McbA1-26),
      determined using nuclear magnetic resonance, reveals that McbA1-26 is an
      amphipathic alpha helix. Mutational analysis of 13 propeptide residues showed
      that Phe8 and Leu12 are essential residues for MccB17 synthetase recognition. A
      domain of the propeptide was putatively identified as the region that interacts
      with the synthetase. CONCLUSIONS: MccB17 synthetase recognizes key hydrophobic
      residues within a helical propeptide, allowing the selective heterocyclization of
      downstream cysteine and serine residues in preproMccB17. The determination of the
      solution structure of the propeptide should facilitate the investigation of other
      functions of the propeptide, including a potential role in antibiotic secretion.

PMID- 9545437
TI  - RB and apoptotic cell death.
AB  - Homeostasis of cell numbers is achieved by balancing the proliferative and death
      states of cells. Proper regulation in a cell requires an accurate coordination
      between these two processes. Indeed, dysregulation of cell cycle progression is
      essential for the initiation of apoptosis. Retinoblastoma protein (RB) is an
      important tumor suppressor and a cell cycle regulator. Most recent studies
      suggest that RB also plays a regulatory role in the process of apoptosis. During
      the onset of apoptosis, the hyperphosphorylated form of RB (p120/hyper) is
      converted to a hypophosphorylated form (p115/hypo), which is mediated by a
      specific protein-serine/ threonine phosphatase activity. Accompanied by the
      internucleosomal fragmentation of DNA, the newly formed p115/hypo/RB is
      immediately cleaved by a protease that has properties of the caspase family.
      During apoptosis, RB is also cleaved in its carboxyl terminus by a caspase-3-like
      activity. By contrast, the unphosphorylated form of RB (p110/unphos) remains
      uncleaved during apoptosis. Further studies suggest that p110/unphos/RB functions
      as an inhibitor of apoptosis. Therefore, regulation of the RB proteolytic
      activities and consequent RB levels is important for the determination of
      cellular fate.

PMID- 9545438
TI  - The essential role of inflammation and induced gene expression in the pathogenic
      pathway of Alzheimer's disease.
AB  - Alzheimer's disease is among the most common diseases of advanced age affecting
      almost one out of ten individuals who survive beyond the age of 65 years, and an
      another 10% for each additional decade of the life-span. The prognosis of the
      disease is an inexorable decline of mental functions leading to complete
      dependence on caretakers in the late stages of the disease. Alzheimer's disease
      will become a steadily increasing financial health-care problem in the
      industrialized world with the increasing longevity and ageing of the population.
      To-date there are no effective therapeutics. However, during the last years
      promising findings suggest that anti-inflammatory treatment strategies might be
      efficient. Here, we will review the experimental and epidemiological findings
      which support the idea that inflammatory mechanisms play an important role in
      Alzheimer's disease pathogenesis. The review of the experimental findings will be
      focussed on the amyloid-associated proteins, alpha1-antichymotrypsin and
      apolipoprotein E, as well as the major cytokines. In addition, the
      epidemiological studies on non-steroidal anti-inflammatory drugs and traumatic
      head injury will be summarized. We hypothesize a pathogenic model for Alzheimer's
      disease in which the expression of amyloid-associated proteins/pathological
      chaperones, induced by inflammatory cytokines, plays an essential role in
      accelerating the disease progress, and suggest potential targets for drug
      discovery based on such a model.

PMID- 9545439
TI  - The neuro-immunological interface in an evolutionary perspective: the dynamic
      relationship between effector and recognition systems.
AB  - The evolutionary perspective indicates that an immune-neuroendocrine effector
      system integrating innate immunity, stress and inflammation is present in
      invertebrates. This defense network, centered on the macrophage and exerting
      primitive and highly promiscuous recognition units, is very effective, ancestral
      and appears to have been conserved throughout evolution from invertebrates to
      higher vertebrates. It would seem that there was a "big bang" in the recognition
      system of lower vertebrates, and T and B cell repertoires, MHC and antibodies
      suddenly appeared. We argue that this phenomenon is the counterpart of the
      increasing complexity of the internal circuitry and recognition units in the
      effector system. The immediate consequences were a progressive enlargement of the
      pathogen repertoire and new problems regarding self/not-self discrimination.
      Probably not by chance, a new organ appeared, capable of purging cells able of
      excessive self recognition. This organ, the thymus, appears to be the result of a
      well known evolutionary strategy of re-using pre-existing material
      (neuroendocrine cells and mediators constituting the thymic microenvironment).
      This bricolage at an organ level is similar to the effect we have already
      described at the level of molecules and functions of the defense network, and has
      a general counterpart at genetic level. Thus, in vertebrates, the conserved
      immune-neuroendocrine effector system remains of fundamental importance in
      defense against pathogens, while its efficiency has increased through synergy
      with the new, clonotipical recognition repertoire.

PMID- 9545440
TI  - In search of an animal model for postmenopausal diseases.
AB  - The purpose of this review is to discuss the use of the aged ovariectomized ewe
      as a cost-effective large animal model to study coronary artery disease (CAD),
      osteoporosis, osteoarthritis (OA), and oral bone loss--conditions seen after
      menopause. Earlier studies from our laboratory showed a significant decline in
      the bone mineral density (BMD) of the iliac crest following ovariectomy in sheep,
      while subsequent studies demonstrated decreased bone loss (measured by dual
      energy X-ray absorptiometry (DXA)) in the lumbar vertebrae following ovariectomy.
      We examined the effects of estrogen deficiency and estrogen therapy on the
      terminal aorta of the aged ovariectomized (OVX) ewes and demonstrated subintimal
      thickening in the distal aorta of animals that were estrogen deficient when
      compared to the control groups. A popular model to study OA is the knee joint of
      sheep following medial or lateral meniscus removal combined with exercise, but
      there is a need for an estrogen-deficient large animal model of OA to study
      articular cartilage changes occurring after menopause. We saw an effect of
      ovariectomy on the biomechanical properties (aggregate modulus and shear modulus)
      of articular cartilage. Estrogen deficiency had a detrimental effect on the
      articular cartilage of the knee even though the cartilage of the OVX animals
      appeared grossly normal. In another study, 13.5 months following ovariectomy, we
      found an increase in estrogen receptor binding capacity of the articular
      cartilage suggesting that articular cartilage is a sex-hormone sensitive tissue.
      There is intense interest in the correlation between systemic osteoporosis and
      bone loss of the mandible and maxilla. We studied mandibular bone loss in OVX
      sheep using DXA. The mean BMD of the OVX group versus sham and estradiol-treated
      animals was lower, indicating that systemic bone loss in OVX ewes may be
      accompanied by oral bone loss. Coronary artery disease, osteoporosis,
      osteoarthritis (OA) and oral bone loss all have a major impact on women's heath
      after menopause and we found that certain characteristics of these conditions can
      be reproduced in the skeletally mature or aged estrogen-deficient sheep. It is
      premature to promote the sheep as the only model to study estrogen deficiency and
      the many differences from small animal omnivores and non-human primates need to
      be overcome and a search for more economical models must continue. This model,
      however, may offer the opportunity to study postmenopausal conditions and the
      safety and efficacy of new therapeutic agents.

PMID- 9545441
TI  - Mapper: an intelligent restriction mapping tool.
AB  - MOTIVATION: To determine the most powerful artificial intelligence techniques for
      automated restriction mapping, and use them to create a powerful multiple-enzyme
      restriction mapping tool. RESULTS: The most effective search engine utilized
      model-driven exhaustive search and a form of binary logic pruning based on
      Pratt's separation theory. Additional experimentation led to the development of
      an input preprocessing module which significantly speeds up searches, and an
      output post-processing module which enables users to analyze large solution sets
      and reduce their apparent complexity. AVAILABILITY: An executable version of the
      resultant tool, Mapper, can be downloaded from our Web site
      (http://www.ai.eecs.uic.edu) by selecting the 'Software' option. CONTACT:
      nelson@eecs.uic.edu (http://www.ai.eecs.uic.edu/nelson).

PMID- 9545442
TI  - Design and implementation of a CORBA-based genome mapping system prototype.
AB  - MOTIVATION: CORBA (Common Object Request Broker Architecture), as an open
      standard, is considered to be a good solution for the development and deployment
      of applications in distributed heterogeneous environments. This technology can be
      applied in the bioinformatics area to enhance utilization, management and
      interoperation between biological resources. RESULTS: This paper investigates
      issues in developing CORBA applications for genome mapping information systems in
      the Internet environment with emphasis on database connectivity and graphical
      user interfaces. The design and implementation of a CORBA prototype for an animal
      genome mapping database are described. AVAILABILITY: The prototype demonstration
      is available via: http://www.ri.bbsrc.ac.uk/ark_corba/. CONTACT:
      jian.hu@bbsrc.ac.uk

PMID- 9545443
TI  - Prediction of MHC class II-binding peptides using an evolutionary algorithm and
      artificial neural network.
AB  - MOTIVATION: Prediction methods for identifying binding peptides could minimize
      the number of peptides required to be synthesized and assayed, and thereby
      facilitate the identification of potential T-cell epitopes. We developed a
      bioinformatic method for the prediction of peptide binding to MHC class II
      molecules. RESULTS: Experimental binding data and expert knowledge of anchor
      positions and binding motifs were combined with an evolutionary algorithm (EA)
      and an artificial neural network (ANN): binding data extraction --> peptide
      alignment --> ANN training and classification . This method, termed PERUN, was
      implemented for the prediction of peptides that bind to HLA-DR4(B1*0401). The
      respective positive predictive values of PERUN predictions of high-, moderate-,
      low- and zero-affinity binders were assessed as 0.8, 0.7, 0.5 and 0.8 by cross
      validation, and 1.0, 0.8, 0.3 and 0.7 by experimental binding. This illustrates
      the synergy between experimentation and computer modeling, and its application to
      the identification of potential immunotherapeutic peptides. AVAILABILITY:
      Software and data are available from the authors upon request. CONTACT:
      vladimir@wehi.edu. au

PMID- 9545444
TI  - Analysis of DNA curvature using artificial neural networks.
AB  - MOTIVATION: Our aim is to utilize an artificial neural network (ANN) for the
      prediction of DNA curvature in terms of retardation anomaly. RESULTS: An ANN
      capturing the role of phasing, increased helix flexibility, run of poly(A) tracts
      and flanking base pair effects in determining the extent of DNA curvature has
      been developed. The network predictions validate the known experimental results
      and also explain how the base pairs other than ApA affect the curvature. The
      results suggest that ANN can be used as a model-free tool for studying DNA
      curvature. AVAILABILITY: The optimal weights and the procedure to compute the
      retardation anomaly value are available on request from the authors. CONTACT:
      bdk@ems. ncl.res.in

PMID- 9545445
TI  - Feature selection for genetic sequence classification.
AB  - MOTIVATION: Most of the existing methods for genetic sequence classification are
      based on a computer search for homologies in nucleotide or amino acid sequences.
      The standard sequence alignment programs scale very poorly as the number of
      sequences increases or the degree of sequence identity is <30%. Some new
      computationally inexpensive methods based on nucleotide or amino acid
      compositional analysis have been proposed, but prediction results are still
      unsatisfactory and depend on the features chosen to represent the sequences.
      RESULTS: In this paper, a feature selection method based on the Gamma (or near
      neighbour) test is proposed. If there is a continuous or smooth map from feature
      space to the classification target values, the Gamma test gives an estimate for
      the mean-squared error of the classification, despite the fact that one has no a
      priori knowledge of the smooth mapping. We can search a large space of possible
      feature combinations for a combination which gives a smallest estimated mean
      squared error using a genetic algorithm. The method was used for feature
      selection and classification of the large subunits of rRNA according to RDP
      (Ribosomal Database Project) phylogenetic classes. The sequences were represented
      by dinucleotide frequency distribution. The nearest-neighbour criterion has been
      used to estimate the predictive accuracy of the classification based on the
      selected features. For examples discussed, we found that the classification
      according to the first nearest neighbour is correct for 80% of the test samples.
      If we consider the set of the 10 nearest neighbours, then 94% of the test samples
      are classified correctly. AVAILABILITY: The principal novel component of this
      method is the Gamma test and this can be downloaded compiled for Unix Sun 4,
      Windows 95 and MS-DOS from http://www.cs.cf.ac.uk/ec/ CONTACT:
      s.margetts@cs.cf.ac.uk

PMID- 9545446
TI  - DIVCLUS: an automatic method in the GEANFAMMER package that finds homologous
      domains in single- and multi-domain proteins.
AB  - MOTIVATION: Large-scale determination of relationships between the proteins
      produced by genome sequences is now common. All protein sequences are matched and
      those that have high match scores are clustered into families. In cases where the
      proteins are built of several domains or duplication modules, this can lead to
      misleading results. Consider the very simple example of three proteins: 1, formed
      by duplication modules A and B; 2, formed by duplication modules B' and C; and 3,
      formed by duplication modules C' and D. Duplication modules B and B' are
      homologous, as are C and C'. Matching the sequences of 1, 2 and 3 followed by
      simple single-linkage clustering would put all three in the same family, even
      though proteins 1 and 3 are not related. This is because the different parts of 2
      match 1 and 3. This paper describes a procedure, DIVCLUS, that divides such
      complex clusters of partially related sequences into simple clusters that contain
      only related duplication modules. In the example just given, it would produce two
      groups of sequences: the first with domains B of sequence 1 and B of sequence 2,
      and the second with domain C of sequence 2 and C of sequence 3. DIVCLUS is part
      of a package called GEANFAMMER, for GEnome ANalysis and protein FAMily MakER. The
      package automates the detection of families of duplication modules from a protein
      sequence database. RESULTS: DIVCLUS has been applied to the division of single
      linkage clusters generated from the protein sequences of six completely sequenced
      bacterial genomes. Out of 12 013 genes in these six genomes, 4563 single- and
      multi-domain sequences formed 1071 complex clusters. Application of the DIVCLUS
      program resolved these clusters into 2113 clusters corresponding to single
      duplication modules. AVAILABILITY: The perl5 program and its documentation are
      available at the following address: http://www.mrc-lmb.cam.ac.uk/genomes/ and by
      anonymous ftp at ftp.mrc-lmb.cam.ac.uk in the directory /pub/genomes/Software/.
      CONTACT: sat@mrc-lmb.cam.ac.uk; jong@mrc-lmb. cam.ac.uk

PMID- 9545447
TI  - A major component approach to presenting consensus sequences.
AB  - MOTIVATION: Summarizing and displaying the information contained in a set of
      aligned sequences is an important aid to identifying patterns within the
      sequences. A variety of forms of consensus sequences have been used previously to
      provide this information. However, these methods can cause a loss of information
      or introduce ambiguities into the consensus sequence, and some graphical
      approaches may become difficult to interpret due to visual distortion. RESULTS:
      We have developed a method to present a more precise and graphically clear view
      of a consensus sequence by using an approach based on defining the major
      components at each position in a sequence set. The major components are given in
      an ordered list and their frequencies are shown as histograms which can be colour
      coded to reflect conservative groupings. Minor components, a one-line character
      based consensus sequence and information statistics can also be presented. As
      well as identifying the dominant sources of variation and conservation in the
      sequence set, the method also enables similarities and differences between
      subgroups of a sequence set to be readily assessed. AVAILIABILITY: On request
      from the authors. CONTACT: bcsmith@usthk.ust.hk, hxue@usthk. ust.hk

PMID- 9545448
TI  - Rose: generating sequence families.
AB  - MOTIVATION: We present a new probabilistic model of the evolution of RNA-, DNA-,
      or protein-like sequences and a software tool, Rose, that implements this model.
      Guided by an evolutionary tree, a family of related sequences is created from a
      common ancestor sequence by insertion, deletion and substitution of characters.
      During this artificial evolutionary process, the 'true' history is logged and the
      'correct' multiple sequence alignment is created simultaneously. The model also
      allows for varying rates of mutation within the sequences, making it possible to
      establish so-called sequence motifs. RESULTS: The data created by Rose are
      suitable for the evaluation of methods in multiple sequence alignment computation
      and the prediction of phylogenetic relationships. It can also be useful when
      teaching courses in or developing models of sequence evolution and in the study
      of evolutionary processes. AVAILABILITY: Rose is available on the Bielefeld
      Bioinformatics WebServer under the following URL: http://bibiserv.TechFak.Uni
      Bielefeld.DE/rose/ The source code is available upon request. CONTACT:
      folker@TechFak.Uni-Bielefeld.DE

PMID- 9545449
TI  - Automated protein sequence database classification. I. Integration of
      compositional similarity search, local similarity search, and multiple sequence
      alignment.
AB  - MOTIVATION: Genome sequencing projects require the periodic application of
      analysis tools that can classify and multiply align related protein sequence
      domains. Full automation of this task requires an efficient integration of
      similarity and alignment techniques. RESULTS: We have developed a fully automated
      process that classifies entire protein sequence databases, resulting in alignment
      of the homologous sequences. The successive steps of the procedure are based on
      compositional and local sequence similarity searches followed by multiple
      sequence alignments. Global similarities are detected from the pairwise
      comparison of amino acid and dipeptide compositions of each protein. After the
      elimination of all but one sequence from each detected cluster of closely related
      proteins, the remaining sequences are compiled in a suffix tree which is self
      compared to detect local sequence similarities. Sets of proteins which share
      similar sequence segments are then weighted according to their closeness and
      multiply aligned using a fast hierarchical dynamic programming algorithm.
      Computational strategies were devised to minimize computer processing time and
      memory space requirements. The accuracy of the sequence classifications has been
      evaluated for 12 462 primary structures distributed over 341 known families. The
      percentage of sequences with missed or incorrect family assignments was 6.8% on
      the test set. This low error level is only twice that of the manually constructed
      PROSITE database ( 3.4% ) and is substantially better than that found for the
      automatically built PRODOM database ( 34.9% ). AVAILABILITY: The resulting
      database, called DOMO, is available through database search routine SRS at
      Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and
      EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. CONTACT:
      gracy@infobiogen.fr

PMID- 9545450
TI  - Automated protein sequence database classification. II. Delineation Of domain
      boundaries from sequence similarities.
AB  - MOTIVATION: Decomposing each protein into modular domains is a basic prerequisite
      to classify accurately structural units in biological molecules. Boundaries
      between domains are indicated by two similar amino acid sequence segments located
      within the same protein (repeats) or within homologous proteins at notably
      different distances from their respective N- or C-termini. RESULTS: We have
      developed an automated method that combines such positional constraints derived
      from various detected pairwise sequence similarities to delineate the modular
      organization of proteins. The procedure has been applied to a non-redundant data
      set of 26 990 proteins whose sequences were taken from the PIR and SWISS-PROT
      databanks and shared <60% sequence identity amongst pairs. The resultant
      clustering, delineation and multiple alignment of 24 380 sequence fragments
      yielded a new database of 4364 domain families. Comparison of the domain
      collection with that of PRODOM indicates a clear improvement in the number and
      size of domain families, domain boundaries and multiple sequence alignments. The
      accuracy and sensitivity of the method are illustrated by results obtained for
      ankyrin-like repeats and EGF-like modules. AVAILABILITY: The resulting database,
      called DOMO, is available through the database search routine SRS at Infobiogen
      (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL
      (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. CONTACT:
      gracy@infobiogen.fr

PMID- 9545451
TI  - 3DinSight: an integrated relational database and search tool for the structure,
      function and properties of biomolecules.
AB  - MOTIVATION: Although a large amount of information on the structure, function and
      properties of biomolecules is becoming available, it is difficult to understand
      the relationship between them. Thus, we have attempted to create an integrated
      relational database, search and visualization tool, 3DinSight, to help
      researchers to gain insight into their relationship. RESULTS: We have gathered
      data on the structure, function and properties of biomolecules, and implemented
      them into a relational database system. The structural data contain several
      subset data such as protein homologues, protein-DNA complex, in order to enable
      searching within a specific class of data. The functional data include motif
      sequence and mutation data of proteins. Also, various amino acid properties are
      implemented as a relational table. The World Wide Web (WWW) interfaces enable
      users to carry out various kinds of searches among these data. The locations of
      motif sequences and mutations are automatically mapped on the structure, and
      visualized in three-dimensional (3D) space by interactive viewers, VRML (Virtual
      Reality Modeling Language) and RasMol. In the case of VRML, the mapped 3D objects
      are hyper-linked to the corresponding document data. Also, amino acid properties,
      linked with structure, functional and mutation sites, can be displayed as graph
      plots. AVAILABILITY: 3DinSight is freely accessible through the Internet
      (http://www.rtc.riken.go.jp/3DinSight.h tml). CONTACT: sarai@rtc.riken.go.jp

PMID- 9545452
TI  - Estimation and filtering of potential protein-protein docking positions.
AB  - MOTIVATION: Software systems predicting automatically whether and how two
      proteins may interact are highly desirable, both for understanding biological
      processes and for the rational design of new proteins. As a part of a future
      complete solution to this problem, a bundle of programs is presented designed (i)
      to estimate initial docking positions for a given pair of docking candidates,
      (ii) to adjust them, and (iii) to filter them, thus preparing more detailed
      computations of free energies. RESULTS: The system is evaluated on a test set of
      51 co-crystallized complexes aiming at redocking the subunits. It works
      completely automatically and the evaluation is performed using one single set of
      parameters for all complexes in the test set. The number of solutions is fixed to
      50 positions with a median CPU time of 26 min. For 30 complexes, these contain a
      near-correct solution with root mean square deviation ( RMSD ) </=5.0 A, which is
      ranked first in five cases. For all complexes, the best solution is scored on
      rank 16 as the worst case, and has a median RMSD of 4.3 A. Alternatively to this
      initial estimation of docking positions, a global sampling of rotations was
      tested. Whereas this yields top-ranked solutions with RMSD </=3.0 A for all 51
      complexes, the median CPU time increases to 11 h. This shows that this blind
      sampling is not feasible for most applications. AVAILABILITY: The system and its
      components are available on request from the authors. CONTACT:
      friedric@techfak.uni-bielefeld or posch@techfak.uni-bielefeld.de

PMID- 9545453
TI  - Incremental threading optimization (TITO) to help alignment and modelling of
      remote homologues.
AB  - MOTIVATION: Protein sequence comparison has become a major tool for biologists.
      Various methods have been designed in order to reveal even remote homologies
      among proteins. Sequence analyses are powerful, but the lower the identity score,
      the more skill and time are required to perform them accurately. While necessary
      to confirm the sequence comparison through the potential of mean force, sequence
      alignment and molecular modelling are still tedious and time-consuming tasks.
      RESULTS: In order to help sequence threading onto known three-dimensional (3D)
      structures, we have developed a new program, named TITO (Tool for Incremental
      Threading Optimization), which uses a multiple alignment to validate and help the
      refinement of a sequence/structure comparison. It measures the compatibility of a
      family of related sequences with a known 3D structure. The coordinates of the
      common core are extracted, allowing further molecular modelling and 3D survey.
      AVAILABILITY: TITO is available by anonymous ftp at: ftp://lmcp.jussieu.
      fr/pub/tito CONTACT: labesse@lmcp.jussieu.fr SUPPLEMENTARY INFORMATION:
      http://www.lmcp.jussieu.fr/ approximately labesse/TITO/TITO.html

PMID- 9545454
TI  - Fast computation of 3D radon transform via a direct Fourier method.
AB  - MOTIVATION: Arrays of three-dimensional (3D) data are ubiquitous in structural
      biology, biomedicine and clinical imaging. The Radon transform can be implied in
      their manipulation mainly for the solution of the inverse tomographic problem,
      since experimental data are often collected as projections or as samples of the
      Radon space. In electron tomography, new applications of the transform may become
      convenient if a fast and accurate transformation algorithm is adopted. RESULTS: A
      direct Fourier method (DFM) is proposed to compute the 3D Radon transform from a
      sampled function with compact support. This paper describes an already known two
      step algorithm and illustrates its DFM implementation by coordinate
      transformations in 2D Fourier space. The algorithm is easily inverted to obtain a
      density distribution from the Radon transform. The main applications are in the
      field of electron tomography, especially in processes of angular refinement,
      since whatever projection of a structure can be retrieved from its Radon
      transform in a fast and accurate way. The times required to compute a number of
      projections with use of the Radon transform are compared with those required by
      other algorithms. Further uses of the Radon transform can be foreseen in
      applications based on 'projection onto convex sets' (POCS). AVAILABILITY:
      Software is available free of charge upon request to the authors. CONTACT:
      salvator@csmtbo.mi.cnr.it

PMID- 9545455
TI  - Automated management of gene discovery projects.
AB  - The paper reports on programs, organization and Hypertext Mark-up Language (HTML)
      presentation provided by the Hierarchical Automated Gene Identification System
      (HAGIS) designed for managing sequencing projects. AVAILABILITY: On request from
      the authors. CONTACT: st23646@ggr.co.uk

PMID- 9545456
TI  - TOPAL: recombination detection in DNA and protein sequences.
AB  - TOPAL scans a multiple sequence alignment for evidence of recombinant sequences,
      prior to phylogenetic analysis. AVAILABILITY: The TOPAL package may be accessed
      at http://www.bioss.sari.ac.uk/grainne, and by anonymous ftp at ftp.bioss.
      sari.ac.uk in the directory pub/phylogeny/topal. CONTACT:
      grainne@bioss.sari.ac.uk

PMID- 9545457
TI  - STRIRED: graphical analysis of string repeats.
AB  - STRIRED is a toolkit to generate a graphical picture of the distribution of 4- to
      6-mer repeats in a set of user-defined nucleic acid sequences. AVAILABILITY: The
      STRIRED package can be downloaded as self-extracting archive (strired.exe) by
      anonymous FTP from biol.dgbm.unina.it (143.225.252.1), in the directory
      /software/win95/STRIRED. CONTACT: calogero@biol.dgbm.unina. it.

PMID- 9545458
TI  - GeneFIND web server for protein family identification and information retrieval.
AB  - An integrated database and search system has been developed for protein family
      identification and information retrieval, as an approach to undertake the highly
      complex, genomic-scale problem of molecular sequence database search and
      organization. AVAILABILITY: http://diana.uthct.edu CONTACT: wu@uthct.edu

PMID- 9545459
TI  - MEICPS: substitution mutations to engineer intracellular protein stability.
AB  - In MEICPS, results from earlier analyses are utilized to suggest possible
      substitution point mutations to engineer intracellular stability using a given
      sequence or structure of the protein. AVAILABILITY: From bvbreddy@ccmb.ap.nic.in.
      This program needs data from other software, PSA and SSTRUC, available from
      sali@tamika.rockefeller.edu and tom@cryst.bioc.cam.ac.uk, respectively. CONTACT:
      bvbreddy@ccmb.ap.nic.in

PMID- 9545460
TI  - An EXCEL template for calculation of enzyme kinetic parameters by non-linear
      regression.
AB  - MOTIVATION: An EXCEL template has been developed for the calculation of enzyme
      kinetic parameters by non-linear regression techniques. The tool is accurate,
      inexpensive, as well as easy to use and modify. AVAILABILITY: The program is
      available from http://www.ebi.ac.uk/biocat/biocat.html CONTACT: agustin.
      hernandez@bio.kuleuven.ac.be

PMID- 9545461
TI  - A new aspect to the origin and evolution of eukaryotes.
AB  - One of the most important omissions in recent evolutionary theory concerns how
      eukaryotes could emerge and evolve. According to the currently accepted views,
      the first eukaryotic cell possessed a nucleus, an endomembrane system, and a
      cytoskeleton but had an inefficient prokaryotic-like metabolism. In contrast, one
      of the most ancient eukaryotes, the metamonada Giardia lamblia, was found to have
      formerly possessed mitochondria. In sharp contrast with the traditional views,
      this paper suggests, based on the energetic aspect of genome organization, that
      the emergence of eukaryotes was promoted by the establishment of an efficient
      energy-converting organelle, such as the mitochondrion. Mitochondria were
      acquired by the endosymbiosis of ancient alpha-purple photosynthetic Gram
      negative eubacteria that reorganized the prokaryotic metabolism of the
      archaebacterial-like ancestral host cells. The presence of an ATP pool in the
      cytoplasm provided by this cell organelle allowed a major increase in genome
      size. This evolutionary change, the remarkable increase both in genome size and
      complexity, explains the origin of the eukaryotic cell itself. The loss of cell
      wall and the appearance of multicellularity can also be explained by the
      acquisition of mitochondria. All bacteria use chemiosmotic mechanisms to harness
      energy; therefore the periplasm bounded by the cell wall is an essential part of
      prokaryotic cells. Following the establishment of mitochondria, the original
      plasma membrane-bound metabolism of prokaryotes, as well as the funcion of the
      periplasm providing a compartment for the formation of different ion gradients,
      has been transferred into the inner mitochondrial membrane and intermembrane
      space. After the loss of the essential function of periplasm, the bacterial cell
      wall could also be lost, which enabled the naked cells to establish direct
      connections among themselves. The relatively late emergence of mitochondria may
      be the reason why multicellularity evolved so slowly.

PMID- 9545462
TI  - Evolution of the cytochrome c oxidase proton pump.
AB  - The superfamily of quinol and cytochrome c terminal oxidase complexes is related
      by a homologous subunit containing six positionally conserved histidines that
      ligate a low-spin heme and a heme-copper dioxygen activating and reduction
      center. On the basis of the structural similarities of these enzymes, it has been
      postulated that all members of this superfamily catalyze proton translocation by
      similar mechanisms and that the CuA center found in most cytochrome c oxidase
      complexes serves merely as an electron conduit shuttling electrons from
      ferrocytochrome c into the hydrophobic core of the enzyme. The recent
      characterization of cytochrome c oxidase complexes and structurally similar
      cytochrome c:nitric oxide oxidoreductase complexes without CuA centers has
      strengthened this view. However, recent experimental evidence has shown that
      there are two ubiquinone(ol) binding sites on the Escherichia coli cytochrome bo3
      complex in dynamic equilibrium with the ubiquinone(ol) pool, thereby
      strengthening the argument for a Q(H2)-loop mechanism of proton translocation
      [Musser SM et al. (1997) Biochemistry 36:894-902]. In addition, a number of
      reports suggest that a Q(H2)-loop or another alternate proton translocation
      mechanism distinct from the mitochondrial aa3-type proton pump functions in
      Sulfolobus acidocaldarius terminal oxidase complexes. The possibility that a
      primitive quinol oxidase complex evolved to yield two separate complexes, the
      cytochrome bc1 and cytochrome c oxidase complexes, is explored here. This idea is
      the basis for an evolutionary tree constructed using the notion that respiratory
      complexity and efficiency progressively increased throughout the evolutionary
      process. The analysis suggests that oxygenic respiration is quite an old process
      and, in fact, predates nitrogenic respiration as well as reaction-center
      photosynthesis.

PMID- 9545463
TI  - Estimation of the transition/transversion ratio.
AB  - A simple method for estimating the transition/transversion ratio was developed.
      This method can be applied to not only two sequences but also more than two
      sequences. The statistical properties of the method and some other methods were
      examined by numerical computation and computer simulation. The results obtained
      showed that, in terms of bias and variance, the new method gives a better
      estimate of the transition/transversion ratio than do the other examined methods.
      The new method was applied to human and chimpanzee mitochondrial control region
      sequences.

PMID- 9545464
TI  - Patterns of base composition within the genes of Drosophila melanogaster.
AB  - Base composition is not uniform across the genome of Drosophila melanogaster.
      Earlier analyses have suggested that there is variation in composition in D.
      melanogaster on both a large scale and a much smaller, within-gene, scale. Here
      we present analyses on 117 genes which have reliable intron/exon boundaries and
      no known alternative splicing. We detect significant heterogeneity in G+C content
      among intron segments from the same gene, as well as a significant positive
      correlation between the intron and the third codon position G+C content within
      genes. Both of these observations appear to be due, in part, to an overall
      decline in intron and third codon position G+C content along Drosophila genes
      with introns. However, there is also evidence of an increase in third codon
      position G+C content at the start of genes; this is particularly evident in genes
      without introns. This is consistent with selection acting against preferred
      codons at the start of genes.

PMID- 9545465
TI  - Transcription and splicing patterns of M- and O-type P elements in drosophila
      bifasciata, D. helvetica, and scaptomyza pallida 
AB  - RT-PCR was applied to analyze the splicing patterns of P-element-derived mRNAs in
      Drosophila bifasciata, D. helvetica, and Scaptomyza pallida. D. melanogaster was
      used as a control. The experiments revealed that P elements are transcribed in
      all species investigated. However, there are differences in the splicing patterns
      of IVS3, which has to be removed in order to produce transposase mRNA instead of
      repressor mRNA. These differences are observed among species as well as between
      the P element subfamilies, the M and the O type, which coexist in the genomes of
      D. bifasciata and S. pallida. In D. helvetica M-type transposase mRNA was found
      in the germline and repressor mRNA in the soma, as has been previously described
      for the canonical (M-type-related) P element of D. melanogaster. In contrast, in
      S. pallida only repressor mRNA of M-type elements was detected in all tissues. In
      D. bifasciata, M-type IVS3, although activated both in the soma and the germline,
      is never completely excised. Instead, two alternative double-spliced variants
      occur in which two small introns are removed within the IVS3 region. One of these
      variants codes for a protein 12 aa longer than the regular transposase. Taking
      these findings together, transposase production and transpositional activity of M
      type elements seem to be limited to D. helvetica and D. melanogaster, whereas M
      type elements have become immobile in D. bifasciata and S. pallida. Unlike the M
      type, the splicing of O-type transcripts in D. bifasciata and S. pallida follows
      the classical rules of tissue-specific P element regulation: transposase mRNA is
      produced exclusively in the germline whereas repressor mRNA is formed in somatic
      cells. Thus O-type elements are thought to be still transpositionally active in
      both species. This finding is in accordance with the postulated recent transfer
      of O-type elements between the gene pools of D. bifasciata and S. pallida. In
      addition, we were able to show that the IVS3 double-spliced variants of both P
      element types are produced regularily in all species of the genus Drosophila
      investigated so far, but not in S. pallida.

PMID- 9545466
TI  - The molecular clock runs at different rates among closely related members of a
      gene family.
AB  - The serum albumin gene family is composed of four members that have arisen by a
      series of duplications from a common ancestor. From sequence differences between
      members of the gene family, we infer that a gene duplication some 580 Myr ago
      gave rise to the vitamin D-binding protein (DBP) gene and a second lineage, which
      reduplicated about 295 Myr ago to give the albumin (ALB) gene and a common
      precursor to alpha-fetoprotein (AFP) and alpha-albumin (ALF). This precursor
      itself duplicated about 250 Myr ago, giving rise to the youngest family members,
      AFP and ALF. It should be possible to correlate these dates with the phylogenetic
      distribution of members of the gene family among different species. All four
      genes are found in mammals, but AFP and ALF are not found in amphibia, which
      diverged from reptiles about 360 Myr ago, before the divergence of the AFP-ALF
      progenitor from albumin. Although individual family members display an
      approximate clock-like evolution, there are significant deviations-the rates of
      divergence for AFP differ by a factor of 7, the rates for ALB differ by a factor
      of 2.1. Since the progenitor of this gene family itself arose by triplication of
      a smaller gene, the rates of evolution of individual domains were also calculated
      and were shown to vary within and between family members. The great variation in
      the rates of the molecular clock raises questions concerning whether it can be
      used to infer evolutionary time from contemporary sequence differences.

PMID- 9545467
TI  - A concertedly evolving region in Chironomus, unique within the telomere.
AB  - Chromosome terminal, complex repeats in the dipteran Chironomus pallidivittatus
      show rapid concerted evolution during which there is remarkably efficient
      homogenization of the repeat units within and between chromosome ends. It has
      been shown previously that gene conversion is likely to be an important component
      during these changes. The sequence evolution could be a result of different
      processes-exchanges between repeats in the tandem array as well as information
      transfer between units in different chromosomes-and is therefore difficult to
      analyze in detail. In this study the concerted evolution of a region present only
      once per chromosome, at the junction between the telomeric complex repeats and
      the subtelomeric DNA was therefore investigated in the two sibling species C.
      pallidivittatus and C. tentans. Material from individual microdissected
      chromosome ends was used, as well as clones from bulk genomic DNA. On the
      telomeric side of the border pronounced species-specific sequence differences
      were observed, the patterns being similar for clones of different origin within
      each species. Mutations had been transmitted efficiently between chromosomes also
      when adjoining, more distally localized DNA showed great differences in sequence,
      suggesting that gene conversion had taken place. The evolving telomeric region
      bordered proximally to subtelomeric DNA with high evolutionary constancy. More
      proximally localized, subtelomeric DNA evolved more rapidly and showed
      heterogeneity between species and chromosomes.

PMID- 9545468
TI  - Phylogenetic and functional classification of mitogen- and stress-activated
      protein kinases.
AB  - All currently sequenced stress-activated protein kinases (SAPKs), extracellular
      signal-regulated kinases (ERKs), and other mitogen-activated protein kinases
      (MAPKs) were analyzed by sequence alignment, phylogenetic tree construction, and
      three-dimensional structure modeling in order to classify members of the MAPK
      family. Based on this analysis the MAPK family was divided into three subgroups
      (SAPKs, ERKs, and MAPK3) that consist of at least nine subfamilies. Members of a
      given subfamily were exclusively from animals, plants, or yeast/fungi. A single
      signature sequence, [LIVM][TS]XX[LIVM]XT[RK][WY]YRXPX[LIVM] [LIVM], was
      identified that is characteristic for all MAPKs and sufficient to distinguish
      MAPKs from other members of the protein kinase superfamily. This signature
      sequence contains the phosphorylation site and is located on loop 12 of the three
      dimensional structure of MAPKs. I also identified signature sequences that are
      characteristic for each of the nine subfamilies of MAPKs. By modeling the three
      dimensional structure of three proteins for each MAPK subfamily based on the
      resolved atomic structures of rat ERK2 and murine p38, it is demonstrated that
      amino acids conserved in all MAPKs are located primarily in the center of the
      protein around the catalytic cleft. I conclude that these residues are important
      for maintaining proper folding into the gross structure common to all MAPKs. On
      the other hand, amino acids conserved in a given subfamily are located mainly in
      the periphery of MAPKs, indicating their possible importance for defining
      interactions with substrates, activators, and inhibitors. Within these subfamily
      specific regions, amino acids were identified that represent unique residues
      occurring in only a single subfamily and their location was mapped in three
      dimensional structure models. These unique residues are likely to be crucial for
      subfamily-specific interactions of MAPKs with substrates, inhibitors, or
      activators and, therefore, represent excellent targets for site-directed
      mutagenesis experiments.

PMID- 9545469
TI  - Molecular evolution of the globin gene cluster E in two distantly related midges,
      Chironomus pallidivittatus and C. thummi thummi.
AB  - We have studied the evolutionary dynamics of a cluster of insect globin genes by
      comparing the organization and sequence of the gene group in two distantly
      related species, Chironomus pallidivittatus and C. t. thummi. Although the
      general architecture of the globin gene cluster has been conserved, we have found
      an additional, previously undescribed gene (named Cpa F) in C. pallidivittatus
      which shows signs of accelerated sequence evolution at nonsynonymous codon
      positions. This new gene is clearly functional, as demonstrated by Northern
      analysis. Comparison of paralogous and orthologous genes reveals patterns of
      intraspecific sequence homogenization. The head-to-head-oriented globin 3 and 4
      gene pairs in C. t. thummi and the gb 4 gene pair in C. pallidivittatus have been
      efficiently homogenized, probably by gene conversion, in their promoter and
      coding regions. Inverted transcriptional orientation seems to favor efficient
      conversion. The orthologous genes from C. t. thummi and C. pallidivittatus reveal
      different levels of sequence conservation, ranging from 85.3 to 94.7% amino acid
      identity. Surprisingly, globin gene E, for which up to now no corresponding
      protein has been detected in the larval hemolymph of C. t. thummi, shows the
      highest degree of interspecies sequence conservation. This points to an
      essential, as yet unknown function of this globin. The usefulness of globin gene
      comparisons for dating speciation events in Chironomus is discussed.

PMID- 9545470
TI  - Evolutionary rate and genetic heterogeneity of human T-cell lymphotropic virus
      type II (HTLV-II) using isolates from European injecting drug users.
AB  - Seven new Italian and two new British HTLV-II isolates were obtained from
      injecting drug users and the entire long terminal repeat (LTR) region was
      sequenced. Restriction analysis showed that all the Italian isolates are of the
      IIb subtype, whereas the British isolates are of the IIa subtype. To understand
      whether the further differentiation of each two principal HTLV-II subtypes in
      several subgroups could be statistically supported by phylogenetic analysis, the
      neighbor-joining, parsimony, and maximum likelihood methods were used. The
      separation between IIa and IIb is very well supported by all three methods. At
      least two phylogenetic subgroups exist within the HTLV-IIa and at least three
      within the HTLV-IIb subtype. In the present analysis, no statistical support was
      obtained for additional phylogroups. Two particular subgroups seem interesting
      because they include all European and North American injecting drug user strains
      within the IIa and IIb subtypes, respectively. These data confirm that European
      HTLV-II infection among drug users is probably derived from North America. They
      also suggest that though a certain differentiation by restriction analysis in
      different subgroups is possible, carefully interpreted phylogenetic analyses
      remain necessary. Using the likelihood ratio test, a molecular clock for the drug
      user strains was calibrated. A fixation rate between 1.08 x 10(-4) and 2.7 x 10(
      5) nucleotide substitutions per site per year was calculated for the IIa and IIb
      injecting drug user strains. This is the lowest fixation rate so far reported for
      RNA viruses, including for HIV, which typically range between 10(-2) and 10(-4).

PMID- 9545471
TI  - Presence of a fibronectin type III domain in a plant protein.
AB  - A hidden Markov model (HMM) approach was used to identify potential candidates in
      sequence databases for fibronectin type III domains in plants, a kingdom
      heretofore bereft of these structures. Fortuitously, one of the proteins
      uncovered had already had a crystal structure published, allowing direct
      structural confirmation of the existence of this domain in plants.

PMID- 9545472
TI  - Magnetic resonance imaging of the fetus.
AB  - Fetal magnetic resonance imaging (FMRI) has gained considerable interest during
      the last decade, especially in its intracranial applications. Due to its high
      soft-tissue contrast and presumed safety, FMRI should be accepted as a
      complementary technique in prenatal diagnosis, useful either to elucidate
      equivocal findings on routine US studies or to further delineate some
      pathological entities. Normal patterns of fetal brain maturation, as shown by
      FMRI, are described because they are of paramount importance to accurately
      evaluate intracranial diseases. To date, however, FMRI requires specialised
      facilities and should be considered as an evolving clinical research modality and
      performed within precise guidelines in a multidisciplinary approach to prenatal
      pathology.

PMID- 9545473
TI  - MR imaging of fetal cerebral anomalies.
AB  - BACKGROUND: Prenatal diagnosis of fetal brain anomalies relies mainly upon
      ultrasonography. However, even in the most experienced hands, the technique has
      limitations for some difficult diagnoses. MRI is an excellent imaging modality
      for the paediatric and adult brain. OBJECTIVE: To assess the value of prenatal
      MRI when a cerebral anomaly was detected by US and where the prognosis depended
      on the identification of other anomalies undetectable by US, or where fetuses
      were at risk for a CNS lesion even when the US was normal. MATERIALS AND METHODS:
      Four hundred prenatal MRI examinations were performed since 1988, and confirmed
      by postnatal follow-up or pathological examination. Two-thirds of the
      examinations were performed after 25 weeks of gestation, one-third between 21 and
      26 weeks. Fetal immobilisation was obtained by maternal premedication with
      flunitrazepam, administered orally 1 h before the examination. The examinations
      were performed on 1.5 T scanners using one or two surface coils. RESULTS:
      Prenatal MRI allowed the diagnosis of serious unsuspected lesions such as
      neuronal migration disorders, ischaemic and haemorrhagic lesions and the
      abnormalities observed in tuberous sclerosis. It helped to characterise
      ventricular dilatation and anomalies of the corpus callosum and of the posterior
      fossa. CONCLUSIONS: MRI is a valuable complementary tool when prenatal US is
      incomplete, doubtful or limited. Prenatal MRI is particularly useful for the
      detection of ischaemic and haemorrhagic lesions, neuronal migration disorders and
      tuberous sclerosis lesions. Detection of these associated anomalies worsens the
      fetal prognosis, has medico-legal implications and modifies obstetric management.
      Normal prenatal MRI does not exclude an anomaly.

PMID- 9545474
TI  - Intracranial aneurysms in infants and children.
AB  - BACKGROUND: The diagnosis and imaging of pediatric aneurysms has changed since
      the advent of MR and MRA. OBJECTIVE: To update the literature on pediatric
      aneurysms and better define the appropriate work-up of childhood aneurysms in
      1997. MATERIALS AND METHODS: Retrospective review of 21 children (12 boys, 9
      girls) with 25 aneurysms from three institutions over a 20-year period was
      performed. Imaging studies were mixed and included CT (19 patients), MR (11
      patients), MRA (6 patients) and angiography (18 patients). RESULTS: Eighteen of
      25 aneurysms were congenital saccular, 6 were mycotic, and 1 was post-traumatic.
      Of these, 44 % were in the posterior circulation. Nine aneurysms arose from
      distal arterial branches. Forty percent were large (between 1-2.5 cm) and 16 %
      were giant (> 2.5 cm). CT and MR showed hemorrhage, and frequently revealed the
      aneurysms as a focal mass with or without enhancement and flow void. Six children
      had MRA which revealed aneurysms in four patients. All patients with MRA had
      corresponding conventional angiography. CONCLUSION: Characteristics of pediatric
      aneurysms include diversity of type, increased incidence in the posterior fossa,
      peripheral location, and large size. CT, MR and MRA are useful in the diagnosis
      with conventional angiography essential for preoperative planning.

PMID- 9545475
TI  - Ultrasound and MR imaging of fibromatosis colli (sternomastoid tumor of infancy).
AB  - The sonographic and CT findings of fibromatosis colli (sternomastoid tumor of
      infancy) have been described, but the MRI appearance has been reported in only
      one case in which the mass resolved over time. This case describes the detailed
      MRI findings in a biopsy-proven case of fibromatosis colli; the signal intensity
      of the mass on T2-weighted images was slightly less than on gradient-recalled T1
      weighted images, consistent with the presence of some fibrous tissue within the
      muscle mass. The involved portion of the muscle was better defined on MRI than
      sonography. MRI was helpful in demonstrating the signal characteristics of the
      mass; localizing the mass to within the sternocleidomastoid muscle; and
      demonstrating clear surrounding fascial planes with lack of associated
      lymphadenopathy, airway compression, vascular encasement, bone involvement or
      intracranial/intraspinal extension associated with other neck masses.

PMID- 9545476
TI  - Complete calcification of an aneurysm of the vein of Galen.

PMID- 9545477
TI  - Skeletal tuberculosis: dactylitis and involvement of the skull.
AB  - A re-emergence of tuberculosis (TB) is occurring world wide in both developed and
      developing countries. The clinical picture caused by infection with M.
      tuberculosis may simulate many other disease entities and may result in
      unnecessary investigations with a delay in diagnosis and treatment. Skeletal TB
      tends to be isolated to one anatomical site. We report a 6-year-old boy with
      disseminated skeletal TB with dactylitis resembling sickle cell anaemia and lytic
      lesions similar to those which are often seen in neuroblastoma, Langerhans' cell
      histiocytosis and leukaemia. The clinician should be aware that TB can mimic
      almost any disease and recognise the radiographic appearances of skeletal
      tuberculous lesions.

PMID- 9545478
TI  - Reconversion of bone marrow in Gaucher disease treated with enzyme therapy
      documented by MR.
AB  - BACKGROUND: Skeletal complications are responsible for significant morbidity in
      Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow
      infiltration and activity. A way to assess bone marrow improvement is needed
      during enzyme therapy. OBJECTIVE: The purpose of this paper is to assess the
      usefulness of MR in following improvement of abnormal bone marrow in Gaucher
      patients on enzyme therapy. MATERIALS AND METHODS: Three patients aged 2, 7, and
      24 years underwent serial MR scans of the lower extremities before and during
      treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1
      weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two
      patients were imaged after 16 months of therapy, and one patient was imaged after
      6 months of therapy. RESULTS: All patients had improvement in marrow signal
      consistent with partial reconversion to fatty marrow during treatment. The
      findings were more marked after prolonged therapy. T1-weighted images
      demonstrated findings most clearly. CONCLUSION: MR consistently showed
      improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller
      doses of enzyme therapy are the trend, MR can be utilized to determine if therapy
      is effecting a change in the bone marrow.

PMID- 9545480
TI  - The role of ultrasound in the follow-up of postoperative changes after
      pyeloplasty.
AB  - BACKGROUND: Pyeloplasty is an established treatment for pelviureteric junction
      (PUJ) obstruction. The postoperative change in the size of the renal pelvis and
      the kidney parenchyma are variable. OBJECTIVE: To document the changes in renal
      pelvic size and renal parenchymal thickness following pyeloplasty and to
      establish that improvement of both parameters are good markers for improved urine
      flow. MATERIALS AND METHODS: A group of 267 newborns and young infants with
      suspected PUJ obstruction were investigated by ultrasound. Pyeloplasty was
      performed on 102 babies, and 165 patients were followed conservatively.
      Postoperative ultrasonography at 6 and 12 months was available in 88 patients.
      RESULTS: One year after surgery, the renal pelvis was smaller in 76 % of the
      cases. The renal parenchyma was normal or had increased in 92 % of cases.
      CONCLUSION: Resolution of hydronephrosis after surgery is relatively slow, but
      renal parenchymal growth is rapid. Mild postoperative pelvic dilatation is
      frequent and does not indicate continued obstruction.

PMID- 9545479
TI  - Lateral femoral scan: an alternative method for assessing bone mineral density in
      children with cerebral palsy.
AB  - BACKGROUND: Children with cerebral palsy (CP), often nonambulatory and/or on
      anticonvulsants, are at increased risk for fractures. Bone mineral density (BMD)
      measured by the conventional techniques of dual-energy X-ray absorptiometry (DXA)
      often cannot be reliably or easily measured in these patients. OBJECTIVE: To find
      an alternative site to whole body, spine and hip that can be conveniently used to
      measure BMD in CP patients. MATERIALS AND METHODS: Having observed that CP
      patients prefer to lie on their sides, we explored measuring BMD at the distal
      femur in the lateral projection. A total of 92 scans were performed without
      sedation in 34 children and adolescents with CP, aged 4-19 years. Four femoral
      shaft subregions were created: two trabecular and two cortical. RESULTS: The
      coefficients of variation (CV %) were generally higher for opposite-side
      comparisons (n = 12 patients) than for same-side comparisons (n = 16 patients).
      For intra- and interobserver analyses, CV % were higher for cortical regions than
      for trabecular regions. Overall, the CV % were similar to those for hip and
      spine. CONCLUSION: This peripheral site in the femur should be considered as an
      alternative for patients with CP when whole-body, hip and spine DXA are not
      practical.

PMID- 9545481
TI  - Cystosonography with echocontrast: a new imaging modality to detect
      vesicoureteric reflux in children.
AB  - BACKGROUND: Conventionally, vesicoureteric reflux (VUR) is assessed by
      fluoroscopic micturating cystourethrography (MCU) or direct or indirect
      radionuclide cystography (RNC). There is preliminary experience with contrast
      enhanced sonography for the detection of VUR. OBJECTIVE: To evaluate the
      usefulness of contrast-enhanced ultrasonography using galactose suspension as an
      echogenic contrast medium. MATERIALS AND METHODS: In this study a galactose
      suspension was instilled into the bladder in 58 neonates, infants and children
      along with normal saline to detect the presence and the severity of VUR through
      the enhanced US signal. The results were compared with those of MCU and RNC. One
      ml/kg of echocontrast in the neonatal age group, and 0.5 ml/kg thereafter, were
      slowly instilled through a 4-F catheter after preliminary supine and prone
      urinary tract US. Indications for the investigation were antenatally diagnosed
      pyelectasis (21 cases) and pyelonephritis (37 cases). In 38 patients echocontrast
      cystosonography (ECS) was performed before, and in 20 patients after, MCU or RNC.
      RESULTS: ECS detected 76 refluxing units in 50 patients. In eight patients, no
      VUR was shown, and none of these developed a urinary tract infection in 18 months
      of follow-up. In 43 patients, MCU or RNC detected 62 refluxing units, while in 15
      no VUR was shown. Taking MCU as the gold standard and using the same grading
      scale, the sensitivity of ECS was 100 %. No side effects were observed. Several
      urinary tract abnormalities were detected by ECS. The male urethra was studied by
      ECS, both by retrograde infusion and during micturition. CONCLUSIONS: ECS is a
      promising imaging technique for detecting and grading VUR without exposing
      patients to ionising radiation.

PMID- 9545482
TI  - Idiopathic arterial calcification of infancy: sonographic and magnetic resonance
      findings with pathologic correlation.
AB  - Idiopathic arterial calcification of infancy is a rare condition characterized by
      extensive arterial calcification and stenoses of large and medium sized arteries.
      We report the sonographic and magnetic resonance angiographic findings of this
      entity and correlate them with the findings at autopsy.

PMID- 9545483
TI  - Pseudolymphoma of the breast in a 4-year-old boy.

PMID- 9545484
TI  - Pulmonary oedema associated with mitral regurgitation: prevalence of predominant
      right upper lobe involvement in children.
AB  - OBJECTIVE: To evaluate the hypothesis that pulmonary venous congestion and oedema
      manifested predominantly in the right upper lobe in children with mitral
      regurgitation occur more frequently than previously thought. MATERIALS AND
      METHODS: Three radiologists retrospectively and independently reviewed the plain
      chest radiographs of 54 children (26 girls, 28 boys, age range 2 days-18 years,
      median 9.5 years) with mitral regurgitation admitted to our institution during a
      5-year period. Radiographs showing pulmonary venous congestion and oedema
      manifested predominantly in the right upper lobe were identified. Clinical
      records of these patients were studied to exclude other causes of pulmonary
      disease. RESULTS: Radiographic signs of pulmonary venous congestion and oedema
      were present in all patients, with redistribution of flow and interstitial oedema
      in 39 patients (72 %) and alveolar oedema in 15 children (28 %). In 12 (22 %) of
      54 children, these findings were localised or predominant in the upper lobe of
      the right lung; none of the children had predominantly left-sided involvement.
      CONCLUSIONS: Pulmonary venous congestion and oedema involving predominantly the
      upper lobe of the right lung in children with mitral regurgitation occur more
      frequently than previously thought. This finding is useful in the differential
      diagnosis of right upper lobe abnormalities, such as pneumonia.

PMID- 9545485
TI  - Magnetic resonance imaging of a left circumflex aortic arch and aberrant right
      subclavian artery: the other vascular ring.
AB  - We present a case of a rare congenital cardiac anomaly. Magnetic resonance
      imaging accurately demonstrated a left circumflex aortic arch. This finding was
      not apparent on a prior conventional angiogram or echocardiography. Magnetic
      resonance imaging documentation of this anomaly is uncommon. Review of the
      embryonic development, clinical presentation of complete and incomplete vascular
      rings, and additional associated cardiac anomalies are discussed. This is one of
      only a few reported cases of a left circumflex aortic arch.

PMID- 9545486
TI  - Spontaneous involution of pulmonary sequestration in children: a report of two
      cases and review of the literature.
AB  - BACKGROUND: Two cases of pulmonary sequestration which regressed spontaneously
      are presented. OBJECTIVE: To demonstrate the value of imaging studies in the
      diagnosis and follow-up of some forms of congenital masses of the lung in
      asymptomatic patients. MATERIAL AND METHODS: We reviewed the clinical records and
      imaging studies of two asymptomatic children, one newborn and the other 3 months
      old, with thoracic masses which demonstrated variable degrees of spontaneous
      involution. RESULTS: Abdominal ultrasound performed on the newborn with a
      palpable mass showed a triangular echogenic mass with a large central feeding
      vessel arising from the aorta. The mass had disappeared on follow-up US exam
      performed 6 years later. CT was performed in the 3-month-old patient with a
      persistent retrocardiac mass. A soft-tissue density mass in the left pulmonary
      base with a large feeding vessel arising from the aorta was visualised on
      contrast-enhanced CT. Five years later, a new CT scan showed significant
      shrinkage of the mass and no vessel. CONCLUSION: Radiological techniques such as
      real-time US with Doppler imaging and contrast-enhanced CT may establish the
      diagnosis of pulmonary sequestration by demonstrating the mass and its systemic
      vessel, thereby eliminating the need for more aggressive imaging procedures.
      Partial or total disappearance of these masses represents a further example of
      involutive pathology and suggests that not all cases of pulmonary sequestration
      should be surgically treated.

PMID- 9545487
TI  - Post-operative intussusception: often an elusive diagnosis.

PMID- 9545488
TI  - MR imaging of a pilomatrixoma.

PMID- 9545489
TI  - Meeting report: 11th International Mouse Genome Conference.

PMID- 9545490
TI  - Location of mouse and human genes corresponding to conserved canine olfactory
      receptor gene subfamilies.
AB  - Olfactory receptors are G protein-coupled, seven-transmembrane-domain proteins
      that are responsible for binding odorants in the nasal epithelium. They are
      encoded by a large gene family, members of which are organized in several
      clusters scattered throughout the genomes of mammalian species. Here we describe
      the mapping of mouse sequences corresponding to four conserved olfactory receptor
      genes, each representing separate, recently identified canine gene subfamilies.
      Three of the four canine genes detected related gene clusters in regions of mouse
      Chromosomes (Chrs) 2, 9, and 10, near previously mapped mouse olfactory genes,
      while one detected a formerly unidentified gene cluster located on mouse Chr 6.
      In addition, we have localized two human gene clusters with homology to the
      canine gene, CfOLF4, within the established physical map of Chr 19p. Combined
      with recently published studies, these data link the four conserved olfactory
      gene subfamilies to homologous regions of the human, dog, and mouse genomes.

PMID- 9545491
TI  - Factors affecting ectopic gene conversion in mice.
AB  - Duplicated genes and repetitive sequences are distributed throughout the genomes
      of complex organisms. The homology between related sequences can promote
      nonallelic (ectopic) recombination, including gene conversion and reciprocal
      exchange. Resolution of these events can result in translocations, deletions, or
      other harmful rearrangements. In yeast, ectopic recombination between sequences
      on nonhomologous chromosomes occurs at high frequency. Because the mammalian
      genome is replete with duplicated sequences and repetitive elements, high levels
      of ectopic exchange would cause aneuploidy and genome instability. To understand
      the factors regulating ectopic recombination in mice, we evaluated the effects of
      homology length on gene conversion between unlinked sequences in the male
      germline. Previously, we found high levels of gene conversion between lacZ
      transgenes containing 2557 bp of homology. We report here that genetic background
      can play a major role in ectopic recombination; frequency of gene conversion was
      reduced by more than an order of magnitude by transferring the transgenes from a
      CF1 strain background to C57BL/6J. Additionally, conversion rates decreased as
      the homology length decreased. Sequences sharing 1214 bp of sequence identity
      underwent ectopic conversion less frequently than a pair sharing 2557 bp of
      identity, while 624 bp was insufficient to catalyze gene conversion at
      significant levels. These results suggest that the germline recombination
      machinery in mammals has evolved in a way that prevents high levels of ectopic
      recombination between smaller classes of repetitive sequences, such as the Alu
      family. Additionally, genomic location appeared to influence the availability of
      sequences for ectopic recombination.

PMID- 9545492
TI  - Structural characterization of the mouse long-chain acyl-CoA dehydrogenase gene
      and 5' regulatory region.
AB  - Long-chain acyl-CoA dehydrogenase (LCAD) is one of four enzymes involved in the
      initial step of mitochondrial beta-oxidation of straight-chain fatty acids. It is
      a member of the acyl-CoA dehydrogenase (Acad or ACAD) gene family of enzymes,
      which also includes very-long-chain (VLCAD), medium-chain (MCAD), and short-chain
      (SCAD) acyl-CoA dehydrogenases. These enzymes all have similar activity but
      differ only in the chain length specificity for their substrate. Mitochondrial
      beta-oxidation provides an important source of energy especially during times of
      fasting. In order to understand the role of LCAD in this pathway, we have cloned
      and characterized the entire mouse (Mus musculus) gene encoding LCAD (Acadl).
      Acadl is a single-copy, nuclear encoded gene approximately 35 kb in size. We have
      sequenced the entire coding region, all intron/exon boundaries, 1.7 kb of its 5'
      regulatory region, and mapped the transcription start site. The gene contains 11
      coding exons ranging in size from 67 bp to 275 bp, interrupted by 10 introns
      ranging in size from 1.0 kb to 6.6 kb in size. The Acadl 5' regulatory region,
      like other members of the Acad family, lacks a TATA or CAAT box and is GC rich.
      This region does contain multiple, putative cis-acting DNA elements recognized by
      either SP1 or members of the steroid-thyroid family of nuclear receptors, which
      has been shown with other members of the ACAD gene family to be important in
      regulated expression. The characterization of the mouse Acadl gene will allow
      further study of LCAD in an in vivo model, and how its expression may be
      coordinated with other members of the Acad gene family.

PMID- 9545493
TI  - Improvement of the porcine transcription map: localization of 33 genes, of which
      24 are orthologous.
AB  - From a resource of porcine ESTs, 52 transcripts were selected for regional
      chromosomal assignments in a somatic cell hybrid panel. Except for six ESTs, the
      chosen transcripts represented genes where the BLASTX database searches showed
      high similarity scores (>90%) with a part of the single pass 5' sequence to
      human, bovine, mouse, or pig entries. PCR primers for hybrid cell analysis of the
      ESTs were positioned in the 3'UTR of the sequences. Confident regional
      assignments to pig chromosomes were obtained for 33 of the 52 porcine ESTs.
      Comparative human mapping data were available for 27 of these. Twenty-four proved
      to be orthologous genes now placed on the porcine transcription map. The data
      presented provide further comparative data for 13 autosomes and the X chromosome.

PMID- 9545494
TI  - CSF2RA, ANT3, and STS are autosomal in marsupials: implications for the origin of
      the pseudoautosomal region of mammalian sex chromosomes.
AB  - The X and Y Chromosomes (Chrs) of eutherian ("placental") mammals share a pseudo
      autosomal region (PAR) that pairs and recombines at meiosis. In humans and other
      eutherians, the PAR contains several active genes and has also been thought to be
      critical for pairing and fertility. In order to explore the origin of the PAR, we
      cloned and mapped three human or mouse pseudoautosomal genes in marsupials, a
      group of mammals that diverged from eutherians about 130 (MYrBP). All three genes
      were autosomal in marsupials, and two co-localized with other human Xp genes on
      an autosome. This implies that the human PAR, like most of human Xp, represents a
      relic of an autosomal region added to both X and Y Chrs between 80 and 150 MYrBP.

PMID- 9545495
TI  - Genetics of susceptibility to radiation-induced apoptosis in colon: two loci on
      chromosomes 9 and 16.
AB  - Apoptosis, a mechanism for removal of genetically damaged cells and for
      maintenance of desired size of cell populations, has been implicated in tumor
      development. Previously, we defined polymorphic loci for susceptibility to
      apoptosis of thymocytes Rapop1, Rapop2, and Rapop3 on mouse Chromosomes 16, 9,
      and 3, respectively, using recombinant congenic CcS/Dem strains, each of which
      contains a random set of 12.5% STS/A genome in the genetic background of
      BALB/cHeA. The STS/A alleles at these loci confer lower susceptibility to
      radiation-induced apoptosis of thymocytes than the BALB/cHeA. In the present
      study, we tested susceptibility of colon crypt cells to radiation-induced
      apoptosis. In contrast to apoptosis in thymus, the STS/A mice were more
      susceptible to apoptosis in colon than the BALB/cHeA. Among the CcS/Dem strains,
      CcS-4, CcS-7, and CcS-16 were more susceptible to apoptosis in colon than the
      BALB/cHeA; in thymus, the CcS-7 mice are less susceptible, and the CcS-4 and CcS
      16 are not different from the BALB/cHeA. Thus, individual CcS/Dem strains showed
      different apoptosis susceptibility in the two organs. Analysis of (CcS-7 x
      BALB/cHeA)F2 hybrids revealed linkage of susceptibility to radiation-induced
      apoptosis of colon crypt cells to two loci on Chrs 9 and 16, to which Rapop2 and
      Rapop1 are mapped. The STS/A allele at the locus on chromosome 9 results in high
      susceptibility to apoptosis of colon crypt cells in mice homozygous for the
      BALB/cHeA allele at the locus on Chr 16. Although these two loci may be identical
      to Rapop1 and Rapop2, they affect apoptosis in colon in a way different from that
      in thymus.

PMID- 9545496
TI  - A genetic linkage map of the mouse chromosome 9 region encompassing the Friend
      virus susceptibility gene 2.

PMID- 9545497
TI  - Evaluation of mouse Sfrp3/Frzb1 as a candidate for the lst, Ul, and Far mutants
      on chromosome 2.

PMID- 9545498
TI  - Mapping, cloning, cDNA sequence, and expression of the gene encoding the mouse
      micromolar calpain large subunit.

PMID- 9545499
TI  - A high-resolution genetic map of mouse chromosome 19 encompassing the muscle
      deficient osteochondrodystrophy (mdf-ocd) region.

PMID- 9545500
TI  - Long CAG/CTG repeats in mice.

PMID- 9545501
TI  - Chromosomal assignments of 19 porcine cDNA sequences by FISH.

PMID- 9545502
TI  - TBX10, a member of the Tbx1-subfamily of conserved developmental genes, is
      located at human chromosome 11q13 and proximal mouse chromosome 19.

PMID- 9545503
TI  - Comparison of the human and murine ATRX gene identifies highly conserved,
      functionally important domains.

PMID- 9545504
TI  - A potential human axonemal dynein heavy-chain gene maps to 17q25.

PMID- 9545505
TI  - Genomic structure of the human KDR/flk-1 gene.

PMID- 9545506
TI  - Cellular apoptosis susceptibility gene capts maps to mouse chromosome 2.

PMID- 9545507
TI  - Isolation and localization of the skeletal myosin heavy chain 2X gene on pig
      chromosome 12q1.4-q1.5.

PMID- 9545508
TI  - The gene encoding PRBP, the mouse homolog of human TRBP, maps to distal
      chromosome 15.

PMID- 9545510
TI  - Role of chondroitin sulfate-hyaluronan interactions in the viscoelastic
      properties of extracellular matrices and fluids.
AB  - The purpose of this study was to investigate the role of chondroitin sulfate
      hyaluronan interactions in the viscoelastic properties of tissues and fluids,
      using capillary and cone-on-plate viscometers. Chondroitin sulfate markedly
      increased the viscosity of hyaluronan solutions at a wide range of hyaluronan
      mass (50-1900 kDa) under physiological conditions of pH, temperature, ionic
      strength and glycosaminoglycan concentration (0.5-40 mg/ml), although the
      viscosity of the chondroitin sulfate solutions themselves was very low. In the
      assay using a cone-on-plate viscometer, chondroitin sulfate increased the
      viscosity of hyaluronan solutions at various shear rates. At low shear rates, the
      viscosity of a chondroitin sulfate (5 mg/ml)-hyaluronan (0.5 mg/ml) mixture was
      about 40% of that of an aggrecan (5 mg/ml)-hyaluronan (0.5 mg/ml) mixture, and at
      2.8-fold higher concentrations, chondroitin sulfate elicited the same effect on
      the viscosity of hyaluronan solutions (5 mg/ml) as an aggrecan monomer. In the
      presence of oscillatory motion, the addition of aggrecan increased the elasticity
      (storage) modulus G' and the viscosity (loss) modulus G" of hyaluronan solutions
      and markedly decreased the loss tangent G"/G' at frequencies corresponding to
      normal joint movements. In contrast, chondroitin sulfate had only a marginal
      effect on the loss tangent G"/G', although it increased G' and G". These findings
      demonstrated that chondroitin sulfate, as well as aggrecan, increases the
      viscosity of hyaluronan solutions, although chondroitin sulfate has less effect
      on the elasticity of hyaluronan solutions than that of aggrecan, and suggest that
      chondroitin sulfate may play an important physiological role in determining the
      viscoelastic properties of extracellular matrices and fluids.

PMID- 9545511
TI  - Molecular cloning and functional expression of chicken luteinizing hormone
      receptor.
AB  - A complementary DNA for chicken luteinizing hormone (LH) receptor containing the
      entire coding region was isolated from chicken F1 granulosa cell cDNA library.
      Nucleotide sequence analysis revealed that there are characteristic GC-rich
      regions around the N-terminal part. Chicken LH receptor consists of a 19-residue
      signal peptide, a 366-residue extracellular domain, a 267-residue region
      containing seven transmembrane segments, and a 76-residue cytoplasmic C-terminal
      tail. The deduced amino acid sequence of the chicken LH receptor shares 67%, 69%,
      and 69% identity with the human, rat and porcine LH receptor sequences,
      respectively, and 51% with chicken FSH receptor. However, an insertion of about
      30 amino acid residues is found in chicken LH receptor in the extracellular
      domain about 44 amino acid residues upstream of the first transmembrane segment.
      In addition, alternative splicing seems likely to occur at the point where the
      insertion starts (nucleotide position 933), resulting in the truncated forms of
      chicken LH receptor with only the extracellular domain. Northern blot analysis
      revealed the presence of multiple transcripts of LH receptor, a major 3.0-kb and
      minor 7-kb and 1.5-kb bands, in chicken F1 to F3 granulosa cells. The full length
      chicken LH receptor cDNA was transiently expressed in COS-7 cells and the
      transfected cells displayed a concentration-dependent increase in cAMP production
      when exposed to varying concentrations of chicken LH. This clearly indicates that
      the cloned cDNA encodes a functional chicken LH receptor protein.

PMID- 9545512
TI  - Saguenay Lac Saint Jean cytochrome oxidase deficiency: sequence analysis of
      nuclear encoded COX subunits, chromosomal localization and a sequence anomaly in
      subunit VIc.
AB  - A biochemically distinct form of cytochrome oxidase (COX) deficiency found in the
      Saguenay region of Quebec is an autosomal recessive trait. The cDNA sequences of
      all 10 nuclear-encoded subunits from a patient's fibroblasts showed normal coding
      sequence. Sequences for subunit VIc in two atypical patients showed a
      heterozygous base substitution. Subunit VIc was localized to chromosome 18.

PMID- 9545513
TI  - The generation and interpretation of positional information within the vertebrate
      myotome.
AB  - How somitic cells become restricted to the muscle fate has been investigated on a
      number of levels. Classical embryological manipulations have attempted to define
      the source of inductive signals that control the formation of the myotome.
      Recently, these studies have converged with others dissecting the role of
      secreted proteins in embryonic patterning to demonstrate a role for specific
      peptides in inducing individual cell types of the myotome. Collectively, these
      investigations have implicated the products of the Wnt, Hedgehog (Hh) and Bone
      morphogenetic protein (Bmp) gene families as key myogenic regulators;
      simultaneously controlling both the initiation of myogenesis and the fate of
      individual myoblasts.

PMID- 9545514
TI  - Molecular cloning of human caveolin 3.
AB  - We isolated a full-length cDNA encoding human caveolin 3, which is 72% and 59%
      homologous to human caveolin 1 and caveolin 2, respectively. Human caveolin 3
      protein contains the 'caveolin signature sequence' and the 33 amino acids
      spanning intramembrane domain common to all caveolins. Northern blot analysis
      indicates that the caveolin 3 transcript is 1.6 kb in size and exclusively
      detectable in muscle tissue.

PMID- 9545515
TI  - cDNA cloning and expression of a novel CYP3A from the Syrian hamster, CYP3A31.
AB  - A clone, encoding a cytochrome P450 protein consisting of 501 amino acids, was
      isolated from a cDNA library constructed from mRNA of Syrian hamster liver. The
      deduced amino acid sequence of this clone showed a high homology (65 to 81%) with
      other mammalian CYP3As and hence, this novel isozyme was named CYP3A31. By
      Northern blotting, using an oligonucleotide specific to CYP3A31, the mRNA for
      this isozyme was shown to be expressed constitutively in liver and induced by
      treatment with phenobarbital but repressed by 3-methylcholanthrene or
      dexamethasone treatments. The increase in mRNA expression by phenobarbital and
      decrease by dexamethasone corresponded to changes in CYP3A protein as analysed by
      Western blotting. These indicate that CYP3A31 might constitute one of the major
      CYP3A isozymes in the hamster.

PMID- 9545516
TI  - Molecular basis for evasion of host immunity and pathogenesis in malaria.
AB  - The article relates the ability of the malaria parasite Plasmodium falciparum to
      avoid a protective immune response, and to induce pathological changes, to the
      properties of specific parasite molecules. Cytoadherence and rosetting are
      important features of cerebral malaria and involve proteins located on the
      surface of the infected red blood cell. Proinflammatory cytokines, particularly
      tumour necrosis factor (TNF), play a role in protective immunity and in inducing
      pathology. Glycophosphatidyl inositol membrane anchors of parasite proteins
      possess insulin like activity and induce TNF synthesis. People subject to
      repeated infections in malaria endemic areas rarely develop complete or sterile
      immunity to malaria. They frequently carry small numbers of parasites in the
      blood, with little symptoms of the disease, illustrating a phenomenon termed semi
      immunity. The basis for semi-immunity is incompletely understood. Malaria
      parasites are susceptible to several immunological effector mechanisms. The
      presence of extensive repetitive regions is a feature of many P. falciparum
      proteins. Available evidence suggests that the structural characteristics of the
      repeats and their location on the surface of parasite proteins promote
      immunogenicity. The repeats may help the parasite evade host immunity by (i)
      exhibiting sequence polymorphism, (ii) preventing the normal affinity and isotype
      maturation of an immune response, (iii) functioning possibly as B cell
      superantigens, (iv) generating predominantly thymus independent antibody
      responses, and (v) acting as a sink for binding protective antibodies. Sequence
      diversity in non-repetitive regions and antigenic variation in parasite molecules
      located on the surface of infected red blood cells also play a role in immune
      evasion. Some sequence homologies between parasite and human proteins may be due
      to molecular mimicry. Homologies in other instances can cause autoimmune
      responses. The immune evasion mechanisms of the parasite need to be considered in
      developing vaccines. Protective immunity and pathology may be delicately balanced
      in malaria.

PMID- 9545517
TI  - The complex between retinol and retinol-binding protein is formed in the rough
      microsomes of liver following repletion of vitamin A-depleted rats.
AB  - Retinol-binding protein (RBP), the plasma transport protein for vitamin A, is
      primarily synthesized in the rough endoplasmic reticulum of the liver. RBP then
      passes through the smooth endoplasmic reticulum and into the Golgi apparatus
      where vesicles form and transport the protein to the cell membrane. When rats
      were depleted of their vitamin A stores, RBP accumulated in the liver microsomes,
      particularly in the rough microsomes. To identify the organelle(s) where retinol
      initially binds to RBP, vitamin A-depleted rats were given an i.v. injection of
      [3H]retinol suspended in Tween 40. After intervals of 2, 3, 4, 5, 6, 8, 10, 15
      and 20 min, liver fractions enriched in rough and smooth microsomes and Golgi
      apparatus were prepared. The retinol/RBP complex (holoRBP) was detected in the
      rough microsomes within 3 min post injection. HoloRBP later appeared in the
      smooth microsomes and Golgi fraction, and then the serum at time intervals
      consistent with the known secretion rate for RBP. HoloRBP was detected in the
      rough microsomes at all times after 3 min, whether or not the complex was present
      in the other subcellular fractions. Thus, the holoRBP complex can form in the
      rough endoplasmic reticulum of the liver.

PMID- 9545518
TI  - Cloning and characterization of vascular endothelial growth factor (VEGF) from
      zebrafish, Danio rerio.
AB  - We have cloned and sequenced a zebrafish (Danio rerio) Vascular Endothelial
      Growth Factor (vegf) cDNA. It encodes a precursor protein of 188 amino acids with
      a putative 23 amino acids signal peptide. Sequence comparison analysis indicates
      that the zebrafish vegf cDNA corresponds to the human VEGF165 isoform and shows
      about 52% identity to human VEGF165 at the amino acid level. A 2.8 kb vegf
      message RNA was detected in adult zebrafish by Northern blot analysis. Expression
      of vegf165 is also detected by RT-PCR in adult fish and throughout the zebrafish
      embryonic development. Whole mount in situ hybridization of zebrafish embryos
      indicates strong expression in four areas of the 18-19 h post-fertilization (hpf)
      embryo: within the anterior central nervous system in the prospective optic
      stalk, in mesoderm overlapping the bilaterally located merging heart fields, in
      mesoderm underlying and flanking the hindbrain posterior to rhombomere 4, and in
      medial regions of the somites. The study of vegf function in zebrafish embryonic
      vascular development will contribute to our understanding of the mechanisms of
      vertebrate endothelial cell differentiation and vasculature formation.

PMID- 9545519
TI  - Characterisation of non-transferrin-bound iron (ferric citrate) uptake by rat
      hepatocytes in culture.
AB  - Under conditions of iron overload plasma transferrin can be fully saturated and
      the plasma can transport non-transferrin-bound Fe which is rapidly cleared by the
      liver. Much of this Fe is complexed by citrate. The aim of the present work was
      to characterise the mechanisms by which Fe-citrate is taken up by hepatocytes
      using a rat hepatocyte cell culture model. The cells, after one day in culture,
      were incubated with 59Fe-labelled Fe-citrate for varying time periods, then
      washed and Fe uptake to the membrane and intracellular compartments of the cell
      was determined by radioactivity measurements. Maximal rates of internalisation of
      Fe occurred at a Fe:citrate molar ratio of 1:100 or greater, a pH of
      approximately 7.4 and an extracellular Ca2+ concentration of 1.0 mM. Fe uptake
      showed Michaelis-Menten kinetics and was a temperature-dependent process. The
      K(m) and Vmax for Fe internalisation by the cells at 37 degrees C were
      approximately 7 microM and 2 nmol/mg DNA/min (25 x 10(6) atoms/cell/min),
      respectively; and the Arrhenius activation energy was 35 kJ/mol. The transition
      metals, Zn2+, Co2+ and Ni2+, inhibited Fe uptake when used at 10 and 100 times
      the concentration of Fe. The rate of Fe internalisation from Fe-citrate was found
      to be approximately 20 times as great as that from Fe-transferrin with Fe
      concentrations of 1 and 2.5 microM for both forms of Fe. The rate of Fe uptake by
      iron-loaded hepatocytes obtained from rats which had been fed carbonyl Fe was not
      significantly different from that by normal hepatocytes. These experiments show
      that rat hepatocytes in primary culture have a high capacity to take up non
      transferrin-bound Fe in the form of Fe-citrate and that uptake occurs by
      facilitated diffusion. The iron transport process does not appear to be regulated
      by cellular Fe levels.

PMID- 9545520
TI  - Molecular analysis of a glucose-regulated gene (grp78) of Neurospora crassa.
AB  - The nucleotide sequence of the gene encoding the glucose-regulated protein 78
      (GRP78) of Neurospora crassa was determined. The ORF codes for a protein of 662
      amino acids (72 kDa) and belongs to the heat shock protein 70 (hsp70) gene
      family, which is characterized by three HSP70 'signature sequences'. The grp78
      gene contains 5 introns. The protein carries the ER retention signal HDEL at its
      carboxy terminus and is most homologous to the KAR2/GRP78 protein of
      Saccharomyces cerevisiae (78%) and to KAR2/BiP of Yarrowia lipolytica (76%). The
      expression of grp78 is constitutive and can be enhanced by starvation, treatment
      with tunicamycin, the calcium ionophore A23187 or elevated temperatures (40
      degrees C). An uninterrupted ORF was found on the reverse cDNA strand of grp78.
      The putative peptide shows 47% homology to the NAD-specific glutamate
      dehydrogenase of Achlya klebsiana.

PMID- 9545521
TI  - Capsulin: a novel bHLH transcription factor expressed in epicardial progenitors
      and mesenchyme of visceral organs.
AB  - Members of the basic helix-loop-helix (bHLH) family of transcription factors have
      been shown to control development and differentiation of a variety of cell types.
      We describe a novel bHLH protein, called capsulin, which is expressed
      specifically in mesodermally-derived cells that surround the epithelium of the
      developing gastrointestinal, genitourinary and respiratory systems during mouse
      embryogenesis. Capsulin transcripts also mark the spiral septum of the heart and
      progenitor cells that give rise to the pericardium and coronary arteries.
      Capsulin shares high homology with a recently identified bHLH protein from
      Drosophila, called bHLH102C, which is expressed in visceral muscle cells that
      surround the midgut. Capsulin binds a specific E-box consensus sequence (CANNTG)
      as a heterodimer with the widely-expressed bHLH protein E12, but it does not
      activate transcription through that sequence on its own. Its restricted
      expression pattern and DNA binding activity suggest that capsulin regulates gene
      expression in specific subtypes of visceral mesodermal cells involved in
      organogenesis and in precursor cells that contribute to the pericardium, coronary
      arteries and regions of the heart.

PMID- 9545522
TI  - Sequencing and high level expression in Escherichia coli of the tropomyosin
      allergen (Der p 10) from Dermatophagoides pteronyssinus.
AB  - The cDNA encoding an allergen from the dust mite Dermatophagoides pteronyssinus
      has been cloned and sequenced. The allergen (Der p 10) is a tropomyosin that
      shared more than 65% identical residues with other invertebrate tropomyosins. The
      final recovery of recombinant Der p 10 from the culture media after a single
      purification step was as much as 26 mg/l. The recombinant allergen is reactive to
      shrimp antitropomyosin IgG antibodies and has a 5.6% frequency of IgE reactivity
      in sera from mite-allergic patients.

PMID- 9545523
TI  - Appearance of cross linked proteins in human atheroma and rat pre-fibrotic liver
      detected by a new monoclonal antibody.
AB  - A new monoclonal antibody against malondialdehyde (MDA)-treated low density
      lipoprotein (LDL) was raised using homogenate of human atheroma as immunogen.
      This antibody, DLH2, was obtained by selecting the clones which did not react to
      native LDL but did react to copper-induced oxidized LDL (OxLDL). DLH2 showed a
      greater reactivity to MDA-LDL than to OxLDL. When LDL was treated with various
      aldehyde containing reagents, treatment of LDL with glutaraldehyde or MDA greatly
      increased the reactivity to the antibody, while LDL treated with 2,4-hexadienal
      or 4-hydroxynonenal was not reactive. Among many proteins tested, high density
      lipoprotein, bovine serum albumin and hemoglobin showed significant reactivity to
      DLH2 after they were treated with MDA or glutaraldehyde. When low density and
      high density lipoproteins treated with MDA were subjected to immunoblot analysis,
      newly formed products larger than the original apolipoproteins were detected with
      the antibody, suggesting that this antibody recognizes aggregated proteins with
      divalent short chain cross linkers. The antigenic materials were shown by
      immunohistochemical analysis to be present in foamy macrophages in human
      atheromatous lesions. DLH2 antigen did not colocalize either with apolipoprotein
      B. Furthermore, we found a massive accumulation of the antigenic material in
      Kupffer cells in the liver of rats treated with alcohol and carbonyl iron, a
      model of hepatic fibrosis due to oxidative stress. These results suggest the
      presence of cross linked proteins in damaged tissues.

PMID- 9545524
TI  - Effects of cyclopentenone prostaglandins and related compounds on insulin-like
      growth factor-I and Waf1 gene expression.
AB  - The molecular pathways by which the cyclopentenone prostaglandins (PGA and PGJ
      series) inhibit cell growth and tumorigenicity are poorly understood. These
      cellular responses may be caused by specific regulation of growth-related and
      stress-induced genes. A variety of prostaglandins were tested for their ability
      to regulate insulin-like growth factor-I (IGF-I) and Waf1 gene expression in C6
      rat glioma cells. The prostaglandins (in order of potency) PGJ2 > PGA1 > PGA2,
      approximately PGD2 >> PGE2 all significantly repressed IGF-I gene expression.
      With the exception of PGE2, the same prostaglandins that repressed IGF-I also
      induced Waf1 gene expression. However, the order of potency for Waf1 induction
      was different than for IGF-I repression: PGA2 > PGA1 approximately PGJ2 > PGD2.
      The different order of potency of the prostaglandins in regulating IGF-I and Waf1
      gene expression suggests that different intracellular signals may be involved in
      regulating the two genes. Augmentation of glutathione levels by pretreatment of
      cells with N-acetyl-L-cysteine attenuated the effect of PGA2 on IGF-I and Waf1
      gene expression. conversely, depletion of the intracellular glutathione pool by
      pretreatment with buthionine sulfoximine potentiated the effect of PGA2 on the
      expression of both genes. These results suggest that conjugation with glutathione
      prevents the regulation of gene expression by PGA2. We also tested the effect of
      several simpler compounds that contain a five-membered ring system on IGF-I and
      Waf1 gene expression. 2-Cyclopenten-1-one, but not cyclopentene or cyclopentene,
      repressed IGF-I and induced Waf1 gene expression, demonstrating the requirement
      for an alpha, beta-unsaturated carbonyl for regulation of the two genes. The
      dione compound 4-cyclopentene-1,3-dione, which has two potentially reactive
      carbons rather than one, was considerably more potent than 2-cyclopentene-1-one
      in repressing IGF-I gene expression (IC50 = 30 microM for 4-cyclopentene-1,3
      dione as compared with 167 microM for 2-cyclopentene-1-one). Additional results
      indicated that diethyl maleate, which has two alpha,beta-unsaturated carbonyls in
      a non-cyclic configuration, also repressed IGF-I gene expression (IC50 = 214
      microM) and induced Waf1 gene expression, indicating that the cyclic structure is
      not required for either effect.

PMID- 9545525
TI  - Oriented growth of calcium oxalate monohydrate crystals beneath phospholipid
      monolayers.
AB  - Oriented calcium oxalate crystals have been grown beneath phospholipid monolayers
      at the air-solution interface from supersaturated calcium oxalate solutions.
      Mature calcium oxalate crystals grown beneath zwitterionic
      dipalmitoylphosphatidylcholine (DPPC) monolayers exhibit the characteristic
      morphology of calcium oxalate monohydrate (COM) crystals with the elongated (101)
      crystal face preferentially oriented parallel to the plane of the monolayer.
      Calcium oxalate crystals grown beneath negatively-charged
      dimyristoylphosphatidylserine (DMPS) monolayers also show a preferential
      orientation with respect to the monolayer; they do not, however, exhibit the
      characteristic COM morphology. Raman spectroscopy strongly suggests that the
      crystals grown beneath either DPPC or DMPS monolayers are the monohydrate phase
      of calcium oxalate; therefore, differences in crystal morphology are not due to
      differences in the crystalline phase. Dimyristoylphosphatidylethanolamine (DMPE),
      dimyristoylphosphatidic acid (DMPA), eicosanoic acid (C20), and eicosanol (C20
      OH) monolayers have also been studied to help elucidate the mechanisms of
      interaction between the lipid monolayers and the calcium oxalate crystals. We
      discuss the roles of lattice matching, hydrogen bonding, stereochemistry and
      electrostatics on crystal orientation and morphology.

PMID- 9545526
TI  - Cloning of capsulin, a basic helix-loop-helix factor expressed in progenitor
      cells of the pericardium and the coronary arteries.
AB  - The basic helix-loop-helix (bHLH) class of transcription factors have been linked
      to a variety of cellular differentiation processes, including myogenesis,
      neurogenesis and hematopoiesis. Here we report the cloning of a new member of
      this family of factors, capsulin. Capsulin was shown to be expressed as early as
      9.5 days of mouse development, with expression in mesodermal cells that are
      progenitors of the epicardium and the coronary arteries. At later stages of
      development, expression is seen in mesenchymal cells that are closely associated
      with the epithelium of the developing lung, gut and kidney. In the proepicardial
      organ, and in the organs where it is expressed in later development, capsulin is
      expressed in cells that give will give rise to smooth muscle. Given the likely
      expression of capsulin in smooth muscle cell progenitors, and significant
      sequence similarity through the bHLH domain, capsulin may be a functional
      ortholog of a Drosophila gene that is expressed in cells that give rise to the
      longitudinal visceral muscle. Capsulin alone or in combination with other bHLH
      proteins, was shown to function as a transcription factor by its ability to
      transactivate both a synthetic and a native promoter, each of which contains
      multiple E-boxes. These studies extend the growing family of bHLH factors that
      are expressed in the early mesoderm, and suggest that capsulin may have a
      functional role in development of the coronary vasculature and organs containing
      epithelial lined tubular structures.

PMID- 9545527
TI  - Stringent structural requirements for anti-Ras activity of S-prenyl analogues.
AB  - The carboxy terminal S-farnesylcysteine of Ras oncoproteins is required for their
      membrane anchorage and transforming activities. We showed previously that S
      farnesylthiosalicylic acid (FTS) affects the membrane anchorage of activated H
      Ras in EJ cells and inhibits their growth. We report here on structural elements
      in S-prenyl derivatives that specifically inhibit the growth of EJ cells, but not
      of untransformed Rat-1 cells. Inhibition of the Ras-dependent extracellular
      signal-regulated protein kinase (ERK), of DNA synthesis and of EJ cell growth
      were apparent after treatment with FTS or its 5-fluoro, 5-chloro and 4-fluoro
      derivatives or with the C20 S-geranylgeranyl derivative of thiosalicylic acid.
      The 4-Cl-FTS analogue was a weak inhibitor of EJ cell growth. The 3-Cl-FTS
      analogue and the FTS carboxyl methyl ester were inactive, as were the C10 S
      geranyl derivative of thiosalicylic acid, farnesoic acid, N-acetyl-S-farnesyl-L
      cysteine and S-farne-sylthiopropionic acid. The structural requirements for anti
      Ras activity of S-prenyl analogues thus appear to be rather stringent. With
      regard to chain length, the C15 farnesyl group linked to a rigid backbone seems
      to be necessary and sufficient. A free carboxyl group in an appropriately rigid
      orientation, as in thiosalicylic acid, is also required. Halogenic substitutents
      on the benzene ring of the thiosalicylic acid are tolerated only at position 5 or
      4. This information may facilitate the design of potent Ras antagonists and
      deepen our understanding of the mode of association of Ras with the plasma
      membrane.

PMID- 9545528
TI  - Characterization of HSE sequences in human Hsp40 gene: structural and promoter
      analysis.
AB  - We have recently cloned a gene of Hsp40, a human homologue of bacterial DnaJ.
      Here we describe the structural and promoter analysis of human Hsp40 gene.
      Analysis of Hsp40 transcripts by 5' and 3' RACE suggested that they have
      different 3' ends, and primer extension studies revealed that the major
      transcription initiation site was localized 47 bp upstream of the ATG translation
      initiation codon. Promoter analysis using deletion derivatives defined a minimal
      region which was active in response to heat shock. The region contained the
      consensus heat shock element (HSE) sequences. The factor bound to these sequences
      was suggested to be a heat shock factor 1 (HSF1) by gel mobility supershift
      assay. In vivo footprinting and promoter analysis revealed that the HSEs in 5'
      upstream region of human Hsp40 gene were composed of eight contiguous (A/G)GAAN
      motifs and were essential for heat shock response. These results indicate that
      Hsp40 is a real heat shock protein. It is also shown that the HSE found in the
      first intron might not be the essential element for heat shock response.

PMID- 9545529
TI  - Expression of two zebrafish homologues of the murine Six3 gene demarcates the
      initial eye primordia.
AB  - The murine homeobox gene Six3 and its Drosophila homologue sine oculis both have
      regulatory functions in eye development. We report the isolation and
      characterization of two zebrafish genes, six3 and six6, that are closely related
      to the murine Six3 gene. Zebrafish six3 may be the structural orthologue, while
      the six6 gene is more similar with respect to embryonic expression. Transcripts
      of both zebrafish six genes are first detected in involuting axial mesendoderm
      and, subsequently, in the overlying anterior neural plate from which the optic
      vesicles and the forebrain will develop. Direct correspondence between six3/six6
      expression boundaries and the optic vesicles indicate essential roles in defining
      the eye primordia. During later stages only the six6 gene displays similar
      features of expression in the eyes and rostral brain as reported previously for
      murine Six3.

PMID- 9545530
TI  - Protective effects of carnosine against protein modification mediated by
      malondialdehyde and hypochlorite.
AB  - Malondialdehyde (MDA) and hypochlorite anions are deleterious products of oxygen
      free-radical metabolism. The effects of carnosine, a naturally occurring
      dipeptide (beta-alanyl-L-histidine), on protein modification mediated by MDA and
      hypochlorite have been studied. MDA and hypochlorite induced formation of
      carbonyl groups and high molecular weight and cross-linked forms of crystallin,
      ovalbumin and bovine serum albumin. The presence of carnosine effectively
      inhibited these modifications in a concentration-dependent manner. It is proposed
      that relatively non-toxic carnosine and related peptides might be explored as
      potential therapeutic agents for pathologies that involve protein modification
      mediated by MDA or hypochlorite.

PMID- 9545531
TI  - Granule associated DNase in T4 and T8 lymphocytes from patients with autoimmune
      diseases.
AB  - The presence of a DNase activity associated with secretion granules was detected
      in T4 and T8 lymphocytes from patients with autoimmune diseases. This activity
      was much higher in primary biliary cirrhosis (PBC) than in Graves' disease (GD)
      and multiple sclerosis (MS) or in healthy subjects. This granule associated DNase
      activity was Ca(2+)-dependent, inhibited by Zn2+, and higher at low pH; its
      molecular weight corresponded to 66kDa; it was more active with double-strand
      than single-strand DNA. Judging from its properties this enzyme differed from the
      three types of endonucleases described as involved in DNA fragmentation (DNase I,
      DNase II and NUC18). Flow cytometry analysis of T lymphocytes showed that DNase
      activity associated with CD4+ lymphocyte granules correlated with the ratio
      CD4+CD45RO+/CD4+CD45RA+ (memory and cytotoxic cells/naive cells, inducers of
      suppression). In contrast, T8 lymphocyte DNase activity correlated with the
      proportion of CD4+ lymphocytes with CD4+CD45RA- phenotype (helpers and inducers
      of cytotoxicity). The possible role of this DNase activity in the mechanisms of
      lysis or apoptosis mediated by CTL is discussed. We suggest that this DNase
      activity could be implicated in some of the alterations of the autoimmune
      response depending on cytotoxic T lymphocytes or T cell inducers of apoptosis.

PMID- 9545532
TI  - Hydroxyl radical formation resulting from the interaction of nitric oxide and
      hydrogen peroxide.
AB  - The highly reactive and cytotoxic hydroxyl radical (OH) was found by
      electrochemical detection to be produced in reactions involving hydrogen peroxide
      (H2O2) and the nitric oxide (NO) donor diethylamine- NO complex. Using aromatic
      hydroxylation of salicylate as a specific indicator of OH, three salicylate
      hydroxylation products were identified; catechol, 2,3- and 2,5-dihydroxybenzoic
      acid. Four additional compounds were detected but not identified. The
      interactions of H2O2 and NO represent a biologically feasible reaction mechanism
      that can account for OH-induced damage in cellular environments where transition
      metal ions are unavailable for participation in the superoxide-mediated Fenton
      reaction. The ability of the NO/H2O2 complex to generate OH independently of iron
      or other transition metals provides a new focus for studies concerned with the
      origin of tissue-specific damage caused by oxygen-derived species.

PMID- 9545533
TI  - Design of metal-binding green fluorescent protein variants.
AB  - Diglycylcysteine motifs bind reduced oxo-compounds of technetium-99m, an
      important isotope in nuclear imaging. We suggested a system for detecting gene
      expression employing the effect of oxo[99mTc]technetate (Tc(V)O3+) transchelation
      and coordination with redox amino acid motifs. DNA fragments encoding
      diglycylcysteine (GGC) binding motifs were prepared by PCR and positioned
      downstream from the green fluorescent protein (GFP) cDNA insert. Using a
      Bluescript (+) vector with the fusion protein positioned under the control of a
      lac promoter, we obtained several E. coli clones expressing the following GFP
      fusion peptides: (1) GFP-P1 bearing a 'hydrophilic' C-terminal peptide
      (LEGGGCEGGC) containing two residues of glutamic acid and C-terminal cysteine (2)
      GFP-P2 carrying a 'hydrophobic' (LGGGGCGGGCGI) peptide (3) a control GFP fusion
      peptide with deleted C-terminal portion. Bacterial lysates obtained from the
      corresponding clones were tested for oxo[99mTc] technetate transchelation from a
      glucoheptonate complex. We found, using a solid phase assay, that radioactivity
      associated with protein lysates obtained from clones expressing GFP-P2 fusions
      were 3-4 fold higher than lysates prepared from a clone expressing a truncated
      GFP fusion protein lacking the C-terminal GGC motifs. High expression of GFP
      fusions (5-21% of total protein) was demonstrated by electrophoresis and verified
      by immunoblotting. Specific association of the isotope with GFP-P2 fusion
      proteins was detected upon incubation of gels in the presence of
      [99mTc]glucoheptonate, while no binding of oxo[99mTc]technetate to GFP-P1 was
      revealed. We demonstrated, by using semi-quantitative autoradiography, that there
      is a 10-fold higher binding of oxotechnetate to GFP-P2 than to a control GFP
      fusion protein. The implications of the study for in vivo gene expression imaging
      are discussed.

PMID- 9545534
TI  - Abnormalities of floor plate, notochord and somite differentiation in the loop
      tail (Lp) mouse: a model of severe neural tube defects.
AB  - Mouse embryos homozygous for the loop-tail (Lp) mutation fail to initiate neural
      tube closure at E8.5, leading to a severe malformation in which the neural tube
      remains open from midbrain to tail. During initiation of closure, the normal
      mouse neural plate bends sharply in the midline, at the site of the future floor
      plate. In contrast, Lp/Lp embryos exhibit a broad region of flat neural plate in
      the midline, displacing the sites of neuroepithelial bending to more lateral
      positions. Sonic hedgehog (Shh) and Netrin1 are expressed in abnormally broad
      domains in the ventral midline of the E9.5 Lp/Lp neural tube, suggesting over
      abundant differentiation of the floor plate. The notochord is also abnormally
      broad in Lp/Lp embryos with enlarged domains of Shh and Brachyury expression. The
      paraxial mesoderm shows evidence of ventralisation, with increased expression of
      the sclerotomal marker Pax1, and diminished expression of the dermomyotomal
      marker Pax3. While the expression domain of Pax3 does not differ markedly from
      wild-type, there is a dorsal shift in the domain of Pax6 expression in the neural
      tube at caudal levels of Lp/Lp embryos. We suggest that the Lp mutation causes
      excessive differentiation of floor-plate and notochord, with over-production of
      Shh from these midline structures causing ventralisation of the paraxial mesoderm
      and, to a lesser extent, the neural tube. Comparison with other mouse mutants
      suggests that the enlarged floor plate may be responsible for the failure of
      neural tube closure in Lp/Lp embryos.

PMID- 9545535
TI  - Regulation of pyruvate dehydrogenase activity and glucose metabolism in post
      ischaemic myocardium.
AB  - Pyruvate dehydrogenase (PDH) is regulated both by covalent modification and
      through modulation of the active enzyme by metabolites. In the isolated heart,
      post-ischaemic inhibition of PDH, leading to uncoupling of glycolysis and glucose
      oxidation and a decrease in cardiac efficiency, has been described. In vivo, post
      ischaemic reperfusion leads to metabolic abnormalities consistent with PDH
      inhibition, but the effects of ischaemia/reperfusion on PDH are not well
      characterized. We therefore investigated PDH regulation following transient
      ischaemia in vivo. In 33 open-chest dogs, the left anterior descending (LAD) was
      occluded for 20 min followed by 4 h reperfusion. In 17 dogs, dichloroacetate
      (DCA) was injected prior to reperfusion, while 16 dogs served as controls. In
      dogs without DCA, glucose oxidation and lactate uptake were lower in reperfused
      than in remote tissue, suggesting reduced flux through PDH. However, percent
      active and total PDH measured in myocardial biopsies were similar in both
      territories, excluding covalent enzyme modification or loss of functional enzyme.
      DCA activated PDH activity similarly in both regions and abolished differences in
      glucose oxidation and lactate uptake. Thus, decreased PDH flux in reperfused
      myocardium does not result from covalent modification or loss of total enzyme
      activity, but more likely from metabolite inhibition of the active enzyme. DCA
      leads to essentially complete activation of PDH, increases overall glucose
      utilization and abolishes post-ischaemic inhibition of glucose oxidation.

PMID- 9545536
TI  - Time resolved absorption study of the reaction of hydroxyurea with sickle cell
      hemoglobin.
AB  - Hydroxyurea has been mixed with hemoglobin S and the reaction was studied using
      electronic absorption spectroscopy as a function of time and wavelength. The rate
      of conversion of oxyhemoglobin S to other species was determined and the nature
      of the reaction products was studied. We also report the formation of
      methemoglobin (and other reaction products) when deoxyhemoglobin S is combined
      with hydroxyurea. The probable increase in the formation of methemoglobin, and
      other potential reaction products such as nitric oxide-hemoglobin, in patients
      with sickle cell anemia who are taking hydroxyurea as a therapeutic drug is
      discussed in terms of the pathophysiology of the disease. It is proposed that
      methemoglobin and possibly nitric oxide-hemoglobin formation may partially
      explain beneficial effects observed in these patients before their levels of
      fetal hemoglobin have increased.

PMID- 9545537
TI  - Repressible antisense inhibition in B lymphocytes.
AB  - The tetracycline-responsive promoter (TRP) system has been adopted in an attempt
      to obtain repressible antisense inhibition in a B lymphocyte model in vitro.
      Levels of secreted IgM protein and mRNA were assessed following the stable
      transfection of B cell line, HO-2.2, with a series of plasmid constructs
      containing antisense or sense target sequence DNA (the 3'-untranslated region
      adjacent to the secreted exon of IgM gene) under the control of the TRP.
      Significant reduction (approximately 90%) in IgM secretion was observed for
      clones transfected with antisense plasmids driven by the TRP and containing the
      IgH enhancer element and the polyadenylation signal sequence from membrane IgM,
      when compared with untransfected and sense controls. Tetracycline (1
      microgram/ml) addition to the culture medium restored the level of IgM secretion
      in these clones to control values, demonstrating repressibility of antisense
      inhibition. Transfection of HO-2.2 cells with antisense (or sense) constructs had
      no detectable effect on membrane IgM protein levels. Hybridisation studies
      demonstrated that decreased protein production observed in the antisense
      transfected clones was most likely attributable to reduced RNA levels. These data
      show that the TRP can be used for repressible and specific antisense inhibition
      of gene product expression in B lymphocytes.

PMID- 9545538
TI  - Duplication and triplication with staggered breakpoints in human mitochondrial
      DNA.
AB  - We identified a tandem duplication and triplication of a mitochondrial DNA
      (mtDNA) segment in the muscle of a 57-year-old man with no evidence of a
      neuromuscular disorder. A large triplication of a mtDNA coding region has not
      been previously reported in humans. Furthermore, the rearrangements (comprising
      10-12% of the muscle mtDNA pool in the propositus) were unique because the
      breakpoints were staggered at both ends (between mtDNA positions 3263-3272 and
      16,065-16,076) and contained no identifiable direct repeats. Both sides of the
      breakpoint were located approximately 35 bp downstream of regions that undergo
      frequent strand displacement by either transcription (positions 3263-3272) or
      replication (positions 16,065-16,076), suggesting that topological changes
      generated by the movement of RNA/DNA polymerases may be associated with the
      genesis of a subclass of mtDNA rearrangements. The presence of low levels of
      these rearrangements in other normal adults also suggest that these mutations are
      not rare. The characterization of these rearrangements shed light on potential
      alternative mechanisms for the genesis of mtDNA rearrangements.

PMID- 9545539
TI  - The Xenopus Emx genes identify presumptive dorsal telencephalon and are induced
      by head organizer signals.
AB  - We have isolated and studied the expression pattern of Xemx1 and Xemx2 genes in
      Xenopus laevis. Xemx genes are the homologues of mouse Emx genes, related to
      Drosophila empty spiracles. They are expressed in selected regions of the
      developing brain, particularly in the telencephalon, and, outside the brain, in
      the otic vesicles, olfactory placodes, visceral arches and the developing
      excretory system. We also report on experiments concerning the tissue and
      molecular signals responsible for their activation in competent ectoderm. Xemx
      genes are activated in ectoderm conjugated with head organizer tissue, but not
      with tail organizer tissue. Furthermore, they are not activated in animal cap
      either by noggin or by Xnr3, thus suggesting that a different inducer or the
      integration of several signals may be responsible for their activation.

PMID- 9545540
TI  - Direct structural evidence for formation of a stem-loop structure involved in
      ribosomal frameshifting in human immunodeficiency virus type 1.
AB  - Programmed ribosomal frameshifting in viral messenger RNA occurs in response to
      neighboring sequence elements consisting of: a frameshift site, a spacer, and a
      downstream enhancer sequence. In human immunodeficiency virus type 1 (HIV-1)
      mRNA, this sequence element has a potential to form either a stem-loop or a
      pseudoknot structure. Based on many mutational studies, the stem-loop structure
      has been proposed for the downstream enhancer region of the HIV-1 mRNA. This
      stimulatory stem-loop structure is separated from the shift site by a spacer of
      seven nucleotides. In contrast, a recent report has proposed an alternative model
      in which the bases in the spacer sequence form a pseudoknot structure as the
      downstream enhancer sequence [Du et al., Biochemistry 35 (1996) 4187-4198.].
      Using UV melting and enzymatic mapping analyses, we have investigated the
      conformation of the sequence region involved in ribosomal frameshifting in HIV-1.
      Our S1, V1, and T1 endonuclease mappings, together with UV melting analysis,
      clearly indicate that this sequence element of the HIV-1 mRNA frameshift site
      forms a stem-loop structure, not a pseudoknot structure. This finding further
      supports the stem-loop structure proposed by many mutational studies for the
      downstream enhancer sequence of the HIV-1 mRNA.

PMID- 9545542
TI  - Interaction between N-terminal domain of H4 and DNA is regulated by the
      acetylation degree.
AB  - To study whether the acetylation of one or more of the four acetylatable lysines
      of histone H4 affects its binding to DNA, we have designed a protection
      experiment with a model system consisting in phage lambda DNA as substrate, StuI
      as restriction endonuclease and histone H4 with different degrees of acetylation
      as the protective agent. It can be deduced from the experimental data that the
      protection afforded by the histone is not dependent on the number of positive
      charges lost by acetylation. Thus, non-acetylated H4 and mono-acetylated H4 cause
      similar protection, while di-acetylation of the histone seems to be the crucial
      step in significantly weakening the interaction between H4 and DNA. This is
      confirmed by the results obtained in protection experiments carried out using H4
      peptide (1-24) with different degrees of acetylation as the protecting agent. As
      restriction enzyme can imitate any trans-acting factor with sequence recognition,
      the di-acetylated isoform of histone H4 can be the starting point, through
      acetylation, to unmask DNA sequences, allowing the accessibility of regulatory
      factors to DNA in the chromatin.

PMID- 9545541
TI  - Induction of prothrombin synthesis by K-vitamins compared in vitamin K-deficient
      and in brodifacoum-treated rats.
AB  - Vitamin K is a group name for a number of prenylated 2-methyl-1,4-naphtoquinones,
      which may differ in their ability to function as a cofactor for prothrombin
      biosynthesis. To quantify the bioactivity of different forms of vitamin K, two
      experimental animal systems are frequently used: vitamin K-deficient rats and
      anticoagulated rats. In this paper both models are compared, and it is shown that
      the results obtained depend on the model used. The main reason for this
      discrepancy is the difference in recycling of vitamin K-epoxide, which results in
      a 500 times higher vitamin K requirement in anticoagulated rats. Absorption and
      hepatic accumulation of long chain menaquinones seem to be restricted to a
      maximum, whereas also the lipophilic nature of long chain menaquinones may hamper
      the quinone-quinol reduction in anticoagulated animals. If these data may be
      extrapolated to patients, food items rich in K1 and MK-4 would be expected to
      influence the stability of oral anticoagulation to a much larger extent than food
      items primarily containing higher menaquinones.

PMID- 9545543
TI  - Identification of new mutations in the adenylosuccinate lyase gene associated
      with impaired enzyme activity in lymphocytes and red blood cells.
AB  - We determined the DNA sequence of the adenylosuccinate lyase (ASL) gene from a 13
      year-old female, who showed a reduced ASL enzymatic activity in lymphocytes and
      red blood cells and suffered from severe psychomotor retardation. The patient was
      the offspring of a non-consanguineous marriage. She was found to be compound
      heterozygous for two missense-mutations located on different alleles (C300-G and
      G1266-T): the first mutation replaces Pro75 by Ala, the second mutation replaces
      Asp397 by Tyr.

PMID- 9545544
TI  - Quantitative measurements of the interaction between monosialoganglioside
      monolayers and wheat germ agglutinin (WGA) by a quartz-crystal microbalance.
AB  - Monosialogangliosides (GM1, GM2, GM3 and GM4) were reconstituted in lipid
      monolayers at the air-water interface. The binding amounts and the initial
      binding rates of wheat germ agglutinin (WGA) to the monosialoganglioside
      monolayers were quantitatively studied by use of a quartz-crystal microbalance
      (QCM). A QCM was horizontally attached to the monolayer from the air phase, and
      the binding behavior (mass increase) was followed by the frequency decrease of
      the QCM. WGA binding affinities for the ganglioside monolayers were influenced by
      hydrophilic head groups of lipid matrices, densities of gangliosides, and
      sequences of oligosaccharide in gangliosides. Binding of WGA to the gangliosides
      reconstituted in a phosphatidylcholine (sphingomyelin and
      distearoylphosphatidylcholine) matrix was strongly suppressed, but not in a
      neutral glycolipids (GlcCer, GalCer, and LacCer),
      dipalmitoylphosphatidylethanolamine, and dipalmitoylphosphatidylethanolamine
      matrix. WGA showed high affinity for monolayers containing 20 mol% gangliosides,
      but only low affinity for 100% ganglioside monolayers. WGA preferably binds to
      gangliosides in the following sequence: GM3 > GM4 >> GM2 = GM1. No affinities of
      WGA for GM2 and GM1 were observed. The combined techniques of monolayer and QCM
      have the advantages of investigating recognition properties of gangliosides.

PMID- 9545545
TI  - Mitochondrial gene expression and respiratory enzyme activities in cardiac
      diseases.
AB  - Respiratory enzyme activities and steady-state level of two mitochondrial-encoded
      transcripts were quantified in heart muscle biopsies from patients suffering
      various types of cardiomyopathies unrelated to mitochondrial primary disorders.
      We have found that although the mitochondrial DNA copy number and the
      concentration of COI and ND4 transcripts remain fairly constant, there is an
      important increase (up to 6-fold) in respiratory enzyme activities affecting to
      several oxidative phosphorylation complexes. Idiopathic dilated cardiomyopathy
      shows the greatest increase, followed by ischemic heart and ventricular
      hypertrophy due to aortic stenosis. The results suggest an energetic compensatory
      mechanism in the heart muscle, in the absence of mitochondrial proliferation or
      activation of mitochondrial gene expression.

PMID- 9545547
TI  - Inhibition of nuclear factor kappa B attenuates proinflammatory cytokine and
      inducible nitric-oxide synthase expression in postischemic myocardium.
AB  - We have previously reported that induction of nuclear factor-kappa B (NF-kappa B)
      occurs in a biphasic manner in postischemic myocardium. Because interleukin-1 (IL
      1), IL-6, tumor necrosis factor-alpha (TNF-alpha), and inducible nitric-oxide
      synthase (iNOS) contain kappa B-response elements, and since transforming growth
      factor-beta 1 (TGF-beta 1) down-modulates both cytokine and iNOS expression, we
      studied their temporal expression during myocardial ischemia/reperfusion (I/R).
      Northern and Western analyses showed low levels of IL-6 and no signal for IL-1
      beta, TNF-alpha and iNOS under basal conditions. Their expression rose
      significantly over sham-operated controls by 1 h reperfusion, and persisted high
      for various periods. Under basal conditions, low levels of TGF-beta 1 were
      detected, which rose significantly at 3 h reperfusion, and remained high until 24
      h reperfusion. Administration of diethyldithiocarbamate (DDC) inhibited induction
      of NF-kappa B and concomitantly the expression of IL-1 beta, IL-6, TNF-alpha as
      well as iNOS. However, expression of TGF-beta was not altered. Our results
      indicate that ischemia/reperfusion induces NF-kappa B, and upregulates kappa B
      response genes. Administration of DDC inhibits NF-kappa B levels, and attenuates
      expression of inflammatory cytokines and iNOS.

PMID- 9545546
TI  - Nkx2-9 is a novel homeobox transcription factor which demarcates ventral domains
      in the developing mouse CNS.
AB  - Nkx homeobox transcription factors are expressed in diverse embryonic cells and
      presumably control cell-type specification and morphogenetic events. Nkx2-9 is a
      novel family member of NK2 genes which lacks the conserved TN-domain found in all
      hitherto known murine Nkx2 genes. The prominent expression of Nkx2-9 in ventral
      brain and neural tube structures defines a subset of neuronal cells along the
      entire neuraxis. During embryonic development, Nkx2-9-expressing cells shift from
      the presumptive floor plate into a more dorsolateral position of the
      neuroectoderm and later become limited to the ventricular zone. Nkx2-9 expression
      overlaps with that of Nkx2-2 but is generally broader. While initially Nkx2-9 is
      expressed in close proximity to sonic hedgehog, its expression domain clearly
      segregates from sonic hedgehog at later developmental stages. The dynamic
      expression pattern of Nkx2-9 in ventral domains of the CNS is consistent with a
      possible role in the specification of a distinct subset of neurons.

PMID- 9545548
TI  - Selection of monoclonal antibodies for probing of functional intermediates in
      incision of UV-irradiated DNA by Uvr(A)BC endonuclease from Escherichia coli.
AB  - Monoclonal antibodies (mAbs) were generated that recognize UvrA and UvrB
      proteins. These proteins are components of the Uvr(A)BC endonuclease, which
      initiates nucleotide excision repair in Escherichia coli. mAbs, which can be used
      for probing of structural intermediates of Uvr(A)BC endonuclease functioning,
      were selected for their ability to: (i) recognize different epitopes; (ii) have a
      high-affinity for native antigenic protein; (iii) preserve functionality of the
      Uvr protein in immunocomplex. The adherence of anti-Uvr mAbs with these criteria
      was verified by additivity and competition tests, and by their influence on the
      ATPase activities of UvrA and UvrB*, the functionally active proteolytic fragment
      of UvrB. Two out of twelve anti-UvrA and seven out of thirteen anti-UvrB/anti
      UvrB* hybridoma lines were shown to satisfy these criteria. Recognition of UvrA
      and UvrB deletion mutant proteins by mAbs was used to map their epitopes.
      Epitopes of A2D1 and A2B1 mAbs were mapped to regions of amino acids 230-281 and
      560-680 of UvrA, respectively. Epitopes of anti-UvrB/UvrB* mAbs were assigned to
      the following amino acid regions of UvrB: B2A1, 8-61; B2C5 and B*2E3, 171-278;
      B2E2, 631-673; B3C1, 1-7 and/or 62-170; B*2B9, 473-630; B*3E11, 379-472. The
      ability of selected mAbs to neutralize the incision function of Uvr(A)BC was
      analyzed. The results are discussed in terms of the applicability of these mAbs
      to probe the structures of intermediates in the functioning of Uvr(A)BC.

PMID- 9545549
TI  - Identification of carbohydrate deficient transferrin forms by MALDI-TOF mass
      spectrometry and lectin ELISABiochim Biophys Acta 1998 Aug 24;1381(3):356.
AB  - Transferrin was isolated from sera of patients with severe alcohol abuse and from
      control sera by affinity chromatography using an immobilized polyclonal antibody
      from sheep, followed by gel filtration. The purified transferrin was then
      separated by MonoQ chromatography. Compared to the controls, sera from heavy
      alcohol consumers showed two additional transferrin peaks, eluting earlier than
      the three main transferrin forms present in all sera. Further analysis of the
      isolated transferrin forms by matrix assisted laser desorption/ionization time of
      flight mass spectrometry (MALDI-TOF-MS) and enzyme linked immunosorbent assay
      with different digoxigenylated lectins (lectin ELISA) revealed that the main
      carbohydrate deficient transferrin (CDT) forms are lacking either one or both of
      the N-Glycan chains.

PMID- 9545550
TI  - Apparent continuity between the messenger transport organizer and late RNA
      localization pathways during oogenesis in Xenopus.
AB  - The localization of RNAs at the vegetal cortex in Xenopus oocytes is a complex
      process, involving at least two different pathways. The early, or messenger
      transport organizer (METRO), pathway, localizes RNAs such as Xlsirts, Xcat2 and
      Xwnt11 during stages 1 and 2 of oogenesis, while the late pathway localizes RNAs
      such as Vg1 during stages 2-4. We demonstrate that the onset of Vg1 localization
      is characterized by its microtubule-independent binding to a subdomain of the
      endoplasmic reticulum (ER). The formation of this unique ER structure is
      intimately associated with the movement of the mitochondrial cloud toward the
      vegetal cortex. In addition, we demonstrate that the mitochondrial cloud contains
      a gamma-tubulin-positive structure that may function as a microtubule organizing
      center for establishing microtubule tracks for Vg1 localization. These data,
      support, although they do not prove, a model in which the development of the late
      pathway machinery relies upon the prior functioning of the early pathway.

PMID- 9545551
TI  - Modulation of DNA polymerases alpha, delta and epsilon by lactate dehydrogenase
      and 3-phosphoglycerate kinase.
AB  - Literature documents that glycolytic enzymes (among them lactate dehydrogenase
      and 3-phosphoglycerate kinase) can reside in nuclei of mammalian cells and exert
      functions in DNA replication, transcription and DNA repair, in addition to their
      role as catalysts in the cytoplasm. Transfer of glycolytic enzymes to cell nuclei
      requires modification, for example phosphorylation. We studied the effects of
      phosphorylated lactate dehydrogenase and 3-phosphoglycerate kinase on (i) UV
      induced DNA repair, using permeabilized human fibroblasts, and (ii) in vitro DNA
      synthesis catalyzed by purified DNA polymerases alpha, delta, and epsilon from
      proliferating rat liver. (i) Phosphorylated lactate dehydrogenase stimulated UV
      induced DNA repair synthesis in normal fibroblasts in a dose-dependent manner;
      the unphosphorylated enzyme slightly inhibited. In repair-deficient xeroderma
      pigmentosum fibroblasts reparative synthesis was not enhanced whether lactate
      dehydrogenase was phosphorylated or not, indicating that reparative DNA synthesis
      must be possible in order to be stimulated. (ii) Activity of purified DNA
      polymerases alpha, delta, and epsilon was differentially stimulated or inhibited,
      according to the phosphorylation status of lactate dehydrogenase. DNA polymerases
      were also modulated by 3-phosphoglycerate kinase, depending on the primer
      templates used which were gapped DNA (mimicking a repair mode of DNA synthesis)
      or single-stranded M13 DNA (representing the replicative mode of DNA synthesis).
      Since glycolytic enzymes in cell nuclei retain binding ability for their
      cofactors, cytoplasmic substrates and inhibitors, a regulatory linkage might
      exist between the energy state of a cell and its replicative and reparative
      functions.

PMID- 9545552
TI  - Reactive iron species in biological fluids activate the iron-sulphur cluster of
      aconitase.
AB  - Low molecular mass iron (LMrFe) can appear in plasma when the transferrin becomes
      fully iron loaded. Such iron poses a risk factor for oxidative damage, and for
      microbial virulence. A previous novel approach to the detection and measurement
      of LMrFe in plasma was the use of the iron-binding properties of the glycopeptide
      antitumour antibiotic bleomycin and its ability to degrade DNA in the presence of
      oxygen, bound iron, and an iron reducing agent. Since bleomycin is a non
      physiological ligand with iron-binding and redox cycling properties, it has been
      suggested that it may not be a valid biological model for detecting and measuring
      LMrFe. To address these concerns we have developed a biological approach to the
      detection and measurement of LMrFe based on the activation of iron-requiring
      aconitase. Parallel measurements, in a variety of clinical conditions in which
      there was a complete saturation of the plasma transferrin, showed that the
      bleomycin assay and the aconitase assay can give similar results for LMrFe.

PMID- 9545553
TI  - Structure and expression of Wnt13, a novel mouse Wnt2 related gene.
AB  - We have identified a novel mouse member of the Wnt family, Wnt13. Among mouse Wnt
      genes, Wnt13 is most closely related to Wnt2. Sequence comparisons and
      chromosomal localization strongly suggest that Wnt13, rather than Wnt2, is the
      mouse orthologue of both the human WNT13 and Xenopus XWnt2 genes. Wnt13 is
      expressed in the embryonic mesoderm during gastrulation. At later stages,
      transcripts are detected in the dorsal midline of the diencephalon and
      mesencephalon, the heart primordia, the periphery of the lung bud and the otic
      and optic vesicles. These data suggest that Wnt13 function might partially
      overlap with those of other Wnt genes in the cell signaling mechanisms
      controlling mesoderm specification during gastrulation and some aspects of brain,
      heart and lung formation.

PMID- 9545554
TI  - Inhibition of migration and proliferation of vascular smooth muscle cells by
      dehydroepiandrosterone sulfate.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) are the most abundant
      steroids in humans, and their serum concentrations progressively decrease with
      age. Although relationships between DHEA(-S) and many age-related illnesses have
      been postulated, the mechanisms for their effects remain unknown, and specific
      receptors for these molecules have not been identified. In this paper, to
      investigate the role of DHEA(-S) in atherogenesis, we studied the proliferation
      and migration of a rabbit vascular smooth muscle cell line, SM-3, in the presence
      of DHEA(-S). Cellular proliferation was inhibited by DHEA-S, and to a lesser
      extent by DHEA. Modified Boyden's chamber assays revealed that DHEA-S inhibited
      the migration of SM-3 cells toward PDGF-BB. In cell attachment assays, DHEA-S
      inhibited the attachment of SM3 cells to fibronectin. It was suggested that the
      inhibitory effect of DHEA-S for SM-3 proliferation and migration was due to the
      decreased interaction with fibronectin. Scatchard analysis revealed the presence
      of two populations of DHEA-S binding sites in the nuclear fraction, and a smaller
      number in the cytosolic fraction. Since the dissociation constant of the higher
      affinity site was similar to the serum DHEA-S concentration in humans (Kd = 5.8
      microM), this binding site could be functional under physiologic conditions.
      These findings suggest that there may be receptor-mediated anti-atherogenic
      actions of DHEA-S.

PMID- 9545555
TI  - Bilirubin as an anti precipitant against copper mediated denaturation of bovine
      serum albumin: formation of copper-bilirubin complex.
AB  - BR forms a beautiful 1:1 greenish complex with Cu2+, having a characteristic
      absorption maximum at 343 nm. To our knowledge, this is the first metal complex
      of bilirubin in aqueous solution so far to be reported. It has also been shown
      that bilirubin (BR) at a concentration more than protein binding capacity has a
      definite role as an anti precipitant of bovine serum albumin by excess copper. At
      a concentration of 1 x 10(-3) moll-1 of the Cu-BR complex, the colour becomes
      greenish black. The rate of formation of this Cu-BR complex when BR extracts
      copper from copper-albumin complex as obtained in our experiment is 34.981 mol-1
      s-1. The Cu-BR complex is stable at a pH ranging from 3.5 to 13.2, and also can
      scavenge radicals like CCl3OO., eaq- and OH.. Addition of excess copper sulfate
      to the solution of this complex causes a greenish black precipitate which can be
      re dissolved in HCl but insoluble in 99% ethanol. The complex does not give
      positive test in Gmelin reaction for bile pigments. The fluorescence spectrum of
      the complex in solution exhibits a peak at 450 nm when excited at 343 nm. The
      precipitated complex is insoluble in a number of solvents like ether, xylene,
      benzene, acetone, chloroform-methanol mixture and DMSO. These results show that
      BR may protect mammals from copper poisoning.

PMID- 9545556
TI  - Repressed beta-1,3-galactosyltransferase in the Tn syndrome.
AB  - The human hematopoietic disorder named Tn syndrome has been ascribed to an
      acquired stem cell mutation resulting in loss of beta-1,3-galactosyltransferase
      activity in affected Tn+ cells of the hematopoietic lineages. Recently, we could
      demonstrate that this deficiency is due to a repression of a functional allele of
      the beta-1,3-Gal-T gene since treatment of Tn+ T-lymphocytes from a patient
      (R.R.) afflicted with the Tn-syndrome with 5-azacytidine or Na n-butyrate
      resulted in re-expression of the Thomsen-Friedenreich (TF) antigen, the product
      of beta-1,3-Gal-T activity [M. Thurnher, S. Rusconi, E.G. Berger. Persistent
      repression of functional allele can be responsible for galactosyltransferase
      deficiency in Tn syndrome. J. Clin. Invest. 91 (1993) 2103-2110]. To reduce these
      observations to a common pathogenetic mechanism responsible for the Tn-syndrome,
      more Tn patients need to be investigated. Here, we describe similar Tn+ T
      lymphocytes cultured ex vivo from patient M.Z. whose Tn+ syndrome was newly
      recognized. Tn+ and TF+ T-lymphocyte cultures were characterized by flow
      cytometry and measurement of beta-1,3-Gal-T and shown to be deficient in Tn+
      cells. Furthermore, Tn+ cells were treated with 5-azacytidine and Na n-butyrate
      as described before. Reoccurrence of beta-1,3-Gal-T activity dependent epitopes
      on the cell surface of Tn+ cells was shown by flow cytometry. These support the
      notion of beta-1,3-Gal-T gene repression as a common pathogenetic mechanism
      underlying the Tn-syndrome.

PMID- 9545557
TI  - Stereochemistry and biological activities of constituents from Cynanchum
      taiwanianum.
AB  - The stereochemistry of new acetophenones, cynandione B-D (2-4), isolated from
      Cynanchum taiwanianum, elucidated by computer modelling calculation and NOESY
      spectrum. It establishes the absolute configurations of cynandiones B-D (2-4) as
      7R; 7"S, 7S; 7"S and 7R; 7"R, respectively. Cynandione B (2) strongly inhibited
      the release of beta-glucuronidase and lysozyme in formyl-methionyl-leucyl
      phenylalanine (fMLP)-stimulated rat neutrophils in a concentration-dependent
      manner with IC50 values of 1.5 +/- 0.2 and 1.6 +/- 0.2 microM, respectively. 2,5
      Dihydroxyacetophenone (6) strongly inhibited the aggregation of washed rabbit
      platelets induced by arachidonic acid in a concentration-dependent manner with an
      IC50 value of about 4.8 microM. In human citrated platelet-rich plasma, 2,5
      dihydroxyacetophenone (6) inhibited the secondary phase, but not the primary
      phase, of aggregation induced by adrenaline and ADP. These results suggest that
      the antiplatelet effect of 2,5-dihydroxyacetophenone (6) is due to inhibition of
      the formation of thromboxane A2.

PMID- 9545558
TI  - Expression of ARNT, ARNT2, HIF1 alpha, HIF2 alpha and Ah receptor mRNAs in the
      developing mouse.
AB  - The basic helix-loop-helix-PAS (bHLH-PAS) protein ARNT is a dimeric partner of
      the Ah receptor (AHR) and hypoxia inducible factor 1 alpha(HIF1 alpha). These
      dimers mediate biological responses to xenobiotic exposure and low oxygen
      tension. The recent cloning of ARNT and HIF1(homologues (ARNT2 and HIF2 alpha)
      indicates that at least six distinct bHLH-PAS heterodimeric combinations can
      occur in response to a number of environmental stimuli. In an effort to
      understand the biological relevance of this combinatorial complexity, we
      characterized their relative expression at a number of developmental time points
      by parallel in situ hybridization of adjacent tissue sections. Our results reveal
      that in general there is limited redundancy in the expression of these six
      transcription factors and that each of these bHLH-PAS members displays a unique
      pattern of developmental expression emerging as early as embryonic day 9.5.

PMID- 9545559
TI  - Concentration-dependent differential effects of N-acetyl-L-cysteine on the
      expression of HSP70 and metallothionein genes induced by cadmium in human
      amniotic cells.
AB  - Cadmium induces the expression of the 70 kDa heat shock protein (HSP70) and
      metallothionein (MT), both of which are considered to be associated with
      intracellular glutathione (GSH) metabolism in the cellular protection mechanism
      against cadmium-induced cellular injury. We determined the effects of N-acetyl-L
      cysteine (NAC), which increases the intracellular GSH levels, on the induction of
      HSP70 and MT gene expression in a cultured cell line of human amniotic cells
      (WISH) exposed to CdCl2. The mRNA level of MT-II, a major isoform of MT genes,
      was more prominently increased than that of HSP70 when WISH cells were exposed to
      CdCl2 (5-15 microM, for 6 h). The treatment of WISH cells with 1.5 and 30 mM NAC
      for 2 h increased the intracellular GSH levels by 1.4- and 3.1-fold,
      respectively. Pretreatment of cells with 30 mM NAC significantly reduced both
      HSP70 and MT-II mRNA levels in the cells exposed to 50 microM CdCl2. This
      concentration of NAC also efficiently suppressed the cadmium-induced lethality.
      On the contrary, pretreatment with 1.5 mM NAC suppressed only the induction of
      HSP70 gene expression in the 50 microM CdCl2-treated cells, and did not inhibit
      the metal toxicity. However, this low concentration of NAC efficiently suppressed
      lipid peroxidation which was increased by 50 microM CdCl2. Furthermore, this low
      concentration of NAC also decreased the CdCl2-induced gene expression of HSP32
      which represents a general response to oxidative stress. Taken together, NAC
      seems to have at least two concentration-dependent functions in WISH cells
      exposed to CdCl2; the low concentration of NAC can suppress the induction of
      HSP70 gene expression as well as the increase of lipid peroxidation via an
      antioxidant pathway, while the high concentration of NAC can suppress the
      induction of MT-II mRNA as well as cadmium-induced cell death. Our present data
      suggest that changes in intracellular redox status, as reflected by GSH
      concentration, have more important effects on the induction of HSP70 mRNA rather
      than that of MT-II mRNA in human amniotic cells exposed to cadmium.

PMID- 9545560
TI  - Expression of NK-2 class homeobox gene Nkx2-6 in foregut endoderm and heart.
AB  - NK-2 class homeobox genes are candidate patterning and lineage regulators in
      diverse organisms. We report here the embryonic expression pattern of murine
      member, Nkx2-6. In keeping with its vertebrate relatives, Nkx2-6 was transcribed
      in ventrolateral embryonic structures. Expression was first detected at E8.0 in
      endodermal walls of the foregut pocket, tissue destined to become pharyngeal
      floor. From E8.0-10.5, transcripts were concentrated in pharyngeal pouches and
      juxtaposed arch ectoderm and mesoderm, as well as in more caudal gut segments.
      Expression was also seen at opposite poles of the developing heart from E8-8.5 in
      posterior myocardial progenitors, then sinus venosa and dorsal pericardium, and
      from E9.5 in outflow tract myocardium.

PMID- 9545561
TI  - Expression of the mouse Fkh1/Mf1 and Mfh1 genes in late gestation embryos is
      restricted to mesoderm derivatives.
AB  - We have compared the expression patterns of the mouse Forkhead homologue 1/
      mesoderm/mesenchyme forkhead 1 (Fkh1/Mf1) gene with that of the highly related
      winged helix gene Mfh1 in late gestation mouse embryos. Transcripts for both
      genes are restricted to derivatives of the mesoderm. Co-expression was found in
      cartilage primordia of the head, ribs, vertebra and bones. However, in several
      structures analyzed, Fkh1/Mf1 signals are lower in the inner layers of the
      developing cartilage than those of Mfh1.

PMID- 9545562
TI  - Antioxidant capacity is correlated with steroidogenic status of the corpus luteum
      during the bovine estrous cycle.
AB  - The reactions of steroid hormone biosynthesis are accompanied by formation of
      oxygen radicals. We determined the levels of some antioxidants and antioxidative
      enzymes at different developmental stages of bovine corpora lutea to examine
      their correlation with steroidogenic status. Plasma progesterone concentrations
      of estrous cycle synchronized cows increased until day 16, and then decreased
      rapidly during luteal regression. The levels of steroidogenic cytochrome P450scc
      and adrenodoxin paralleled the changes in plasma progesterone. Among the
      antioxidative enzymes examined, the SOD and catalase activities showed patterns
      most similar to plasma progesterone. Catalase and SOD activities increased 6-8
      fold from day 6 to 16 of the estrous cycle and then decreased during the luteal
      regression. Ascorbate and beta-carotene showed low but significant correlation
      with P450scc and plasma progesterone levels. The profiles of two lipophilic
      antioxidants in corpora lutea were very different. beta-carotene concentration
      increased by approximately 6 fold from day 6 to 16, and decreased in regressive
      tissue. alpha-tocopherol showed a 3 fold increase between days 6 and 9 followed
      by a rapid decrease. Thus, at the peak of steroidogenesis at mid-luteal phase
      alpha-tocopherol levels decreased, but beta-carotene levels increased. The
      correlation between the levels of some antioxidant enzymes and compounds with
      progesterone levels indicates that antioxidative mechanisms are activated to cope
      with steroidogenesis dependent oxyradical formation in the bovine corpus luteum.

PMID- 9545563
TI  - Purification and characterization of two insecticyanin-type proteins from the
      larval hemolymph of the Eri-silkworm, Samia cynthia ricini.
AB  - Two different biliverdin-binding proteins, designated BBP-I and BBP-II, were
      purified from the larval hemolymph of the Eri-silkworm, Samia cynthia ricini.
      These proteins were readily isolated from the hemolymph of fifth instar larvae
      using two chromatographic steps, hydrophobic interaction chromatography and ion
      exchange chromatography. Both BBPs were easily separated by Q-Sepharose HP column
      chromatography. BBP-I has an apparent molecular weight of 24 kDa, as determined
      by gel-filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). Native BBP-II had a molecular weight of 48 kDa estimated by gel
      filtration. SDS-PAGE revealed a single band with a molecular weight of 26 kDa.
      Moreover, the molecular weights of BBP-I and BBP-II were determined to be 20,468
      and 22,708 by MALDI-TOF/MS (matrix-assisted laser desorption ionization-time of
      flight/mass spectrometry), respectively. On this basis, BBP-I and BBP-II
      molecules are assumed to be a monomer and a dimer, respectively. The blue color
      of BBPs collected from the hemolymph is attributed to the presence of biliverdin
      IX gamma, which is non-covalently and stoichiometrically bound to the apoprotein,
      based on absorbance maxima at 359 and 695 nm in methanol:HCl (95:5, v/v). One
      molecule of BBP-I contains one molecule of biliverdin IX gamma, whereas BBP-II
      contains two molecules of biliverdin IX gamma. The amino acid compositions of BBP
      I and BBP-II are different, although the N-terminal sequences of both BBPs have a
      48% identity. These BBPs were found in the hemolymph of fourth and fifth instar
      larvae. The newly molted fifth instar larvae had the highest concentration of BBP
      I in the hemolymph. This gradually decreased during larval development. In
      contrast to BBP-I, the level of BBP-II was low, and increased slightly at the
      same developmental stage in S. cynthia ricini larvae.

PMID- 9545564
TI  - ERD6, a cDNA clone for an early dehydration-induced gene of Arabidopsis, encodes
      a putative sugar transporter.
AB  - Previously, we constructed a cDNA library from Arabidopsis plants that were
      exposed to dehydration stress for 1 h and obtained the ERD6 clone. Here we report
      that the ERD6 cDNA consists of 1741 bp and encodes a polypeptide of 496 amino
      acids having a predicted molecular weight of 54,354. The putative polypeptide of
      ERD6 is related to those of sugar transporters of bacteria, yeasts, plants and
      mammals. Hydropathy analysis revealed that ERD6 protein has 12 putative
      transmembrane domains and a central hydrophilic region. Sequences that are
      conserved at the ends of the 6th and 12th membrane-spanning domains of sugar
      transporters are also present in ERD6. These data suggest that ERD6 encodes a
      sugar transporter. Genomic Southern blots indicate that the ERD6 gene is a member
      of a multigene family in the Arabidopsis genome. The expression of the ERD6 gene
      was induced not only by dehydration but also by cold treatment.

PMID- 9545565
TI  - Transport mechanisms of a glycoside, p-nitrophenyl-beta-D-glucopyranoside, across
      rat small intestinal brush-border membranes.
AB  - We examined the mechanism of p-nitrophenyl-beta-d-glucopyranoside (p-NP-beta-d
      Glc) transport in brush-border membrane vesicles from rat small intestine. The
      initial uptake rate showed an overshoot phenomenon in the presence of an inwardly
      directed sodium-ion concentration gradient. The overshoot disappeared when the
      sodium-ion concentration gradient was replaced with a potassium ion concentration
      gradient. d-Glucose and p-NP-beta-D-Glc analogues inhibited the uptake, whereas
      uridine, leucine and disaccharide did not. Data on the concentration dependence
      of p-NP-beta-D-Glc uptake indicated that two carrier-mediated systems are
      involved. The uptake via the high-affinity site required an inwardly directed
      sodium-ion concentration gradient, while the uptake via the low-affinity site
      proceeded such a gradient. D-Glucose competitively inhibited the initial uptake
      of p-NP-beta-D-Glc via the high-affinity site with a Ki value of 301 microM. The
      p-NP-beta-D-Glc is transported in the small intestine via both the same carrier
      mediated transport system that takes up D-glucose and a distinct low-affinity
      carrier-mediated transport system.

PMID- 9545566
TI  - Determination of the depth of penetration of the alpha subunit of retinal G
      protein in membranes: a spectroscopic study.
AB  - This paper reports the fluorescence quenching of the alpha subunit of retinal rod
      outer segment G protein (Gtalpha) by vesicles of brominated phospholipids. Two
      different brominated phospholipids with the bromine quencher groups attached at
      the 6-7 and 9-10 positions in one of the fatty acyl chains have been used to
      estimate the depth of penetration of the Gtalpha protein in the lipid vesicles
      using steady-state fluorescence quenching techniques. Our studies provide
      evidence of the interaction between Gtalpha protein, in its active conformation,
      with the lipid vesicles mimicking natural membranes. This study demonstrates that
      in vitro the distance between fluorescent tryptophan site of Gtalpha and the
      membrane surface is approximately 6.5 A.

PMID- 9545567
TI  - Role of cholesterol in the modulation of interdigitation in phosphatidylethanols.
AB  - Phosphatidylethanol (Peth) is formed in biological membranes when ethanol
      replaces water in the transphosphatidylation reaction catalyzed by phospholipase
      D. This charged lipid accumulates in the presence of ethanol, and it has unusual
      properties that can influence membrane structure and function. We have previously
      shown that dimyristoylphosphatidylethanol (DMPeth) and
      dipalmitoylphosphatidylethanol (DPPeth) form the interdigitated gel phase in the
      presence of Tris-HCl [O.P. Bondar, E.S. Rowe, Biophys. J., 71 (1996) 1440-1449].
      In the present investigation, differential scanning calorimetry (DSC) and
      fluorescence have been used to investigate the effect of cholesterol on the phase
      behavior of DPPeth and DMPeth. Our results show that cholesterol prevents the
      formation of the interdigitated phase in the presence of Tris-HCl, and that
      ethanol counters this influence and restores the ability of these lipids to
      interdigitate. Pyrene-PC fluorescence probe was used in this investigation and
      gave results that were in agreement with the conclusions based on the DSC study.

PMID- 9545569
TI  - Quantification of concanavalin A binding to rat brain microsomal membranes
      detected by fluorescence polarization technique.
AB  - A high sensitive method for detecting the change of microsomal membrane surface
      oligosaccharides was developed to study the regulatory role of lipid- or peptide
      linked mannoside of endoplasmic reticulum in synaptic functions. The binding of
      concanavalin A to the microsomal membrane surface was measured quantitatively
      using a microgram-order of rat brain microsomal proteins. The fluorescence
      polarization of concanavalin A (Con A)-fluorescein isothiocyanate (FITC)
      conjugate bound to the membrane was analyzed to quantitate the change of binding
      constant and the number of binding sites. As a control, the non-specific binding
      of bovine serum albumin-FITC conjugate was measured by the same technique. We
      measured the change of fluorescence intensity of membrane-bound FITC conjugates
      by the flow cytometry and found that the intensity of FITC conjugate bound to the
      membrane increased more than that of free form of the probe. We observed that the
      alpha-mannosidase-treatment of rat brain microsomes resulted in the increase of
      binding constant of Con A to the microsomal surface without significant loss of
      binding sites.

PMID- 9545568
TI  - The aminosterol antibiotic squalamine permeabilizes large unilamellar
      phospholipid vesicles.
AB  - The ability of the shark antimicrobial aminosterol squalamine to induce the
      leakage of polar fluorescent dyes from large unilamellar phospholipid vesicles
      (LUVs) has been measured. Micromolar squalamine causes leakage of
      carboxyfluorescein (CF) from vesicles prepared from the anionic phospholipids
      phosphatidylglycerol (PG), phosphatidylserine (PS), and cardiolipin. Binding
      analyses based on the leakage data show that squalamine has its highest affinity
      to phosphatidylglycerol membranes, followed by phosphatidylserine and cardiolipin
      membranes. Squalamine will also induce the leakage of CF from phosphatidylcholine
      (PC) LUVs at low phospholipid concentrations. At high phospholipid
      concentrations, the leakage of CF from PC LUVs deviates from a simple dose
      response relationship, and it appears that some of the squalamine can no longer
      cause leakage. Fluorescent dye leakage generated by squalamine is graded,
      suggesting the formation of a discrete membrane pore rather than a generalized
      disruption of vesicular membranes. By using fluorescently labeled dextrans of
      different molecular weight, material with molecular weight </=4000 g/mol is
      released from vesicles by squalamine, but material with molecular weight
      >/=10,000 is retained. Negative stain electron microscopy of squalamine-treated
      LUVs shows that squalamine decreases the average vesicular size in a
      concentration-dependent manner. Squalamine decreases the size of vesicles
      containing anionic phospholipid at a lower squalamine/lipid molar ratio than pure
      PC LUVs. In a centrifugation assay, squalamine solubilizes phospholipid, but only
      at significantly higher squalamine/phospholipid ratios than required for either
      dye leakage or vesicle size reduction. Squalamine solubilizes PC at lower
      squalamine/phospholipid ratios than PG. We suggest that squalamine complexes with
      phospholipid to form a discrete structure within the bilayers of LUVs, resulting
      in the transient leakage of small encapsulated molecules. At higher
      squalamine/phospholipid ratios, these structures release from the bilayers and
      aggregate to form either new vesicles or squalamine/phospholipid mixed micelles.

PMID- 9545570
TI  - Cloning differentially regulated genes from chondrocytes using agarose gel
      differential display.
AB  - The technique of RNA differential display has been used extensively to clone
      differentially expressed genes from a wide variety of cells and tissues.
      Recently, a simplified method of cloning differential display products, separated
      on agarose gels, was described. Here we report an adaption of this method, using
      total RNA, to clone differentially expressed genes. The approach is simple and
      rapid, and requires only small quantities of total RNA. Utilising this approach,
      we have cloned three differentially regulated genes from chondrocytes stimulated
      to hypertrophy in vitro, and confirmed their pattern of expression by Northern
      blotting. These gene fragments were sequenced and found to correspond to known
      genes, although only one has previously been isolated from chondrocytes.

PMID- 9545571
TI  - Isolation of novel human cDNA (hGMF-gamma) homologous to Glia Maturation Factor
      beta gene.
AB  - A novel full-length human cDNA homologous to Glia Maturation Factor-beta (GMF
      beta) gene was isolated. Sequence analysis of the entire cDNA revealed an open
      reading frame of 426 nucleotides with a deduced protein sequence of 142 amino
      acid residues. The deduced amino acid sequences of its putative product is highly
      homologous to human GMF-beta (82% identity) and named for GMF-gamma. Northern
      blot analysis indicated that a message of 0.9 kb long, but not 4.1 kb of GMF
      beta, is predominantly expressed in human lung, heart, and placenta.

PMID- 9545572
TI  - The development of IL-2 conjugated liposomes for therapeutic purposes.
AB  - A unique immunoliposome has been developed as a drug delivery vehicle for
      immunotherapy. Human recombinant interleukin-2 (IL-2) has been chemically coupled
      to the external surface of small unilamellar vesicles (SUVs) containing
      methotrexate as a candidate immunosuppresive agent in order to specifically
      direct the drug-bearing liposome to activated T-cells expressing the high
      affinity IL-2 receptor. This drug delivery system is designed to deliver an
      immunosuppressive agent to those cells that actively participate in disorders
      such as graft rejection without delivering an effective but potentially toxic
      drug to all cells of the immune system as well as other healthy tissues. IL-2 was
      chemically modified with succinimidyl 4-[p-maleidophenyl butyrate](SMPB) while
      the receptor binding domain on IL-2 was protected by monoclonal anti-IL-2 bound
      to Protein A-Silica Gel. The antibody recognizes the receptor binding domain of
      the IL-2 molecule. The IL-2 was derivatized with S-succinimidyl-S-thioacetate
      (SATA) in order to add an acetyl thioester group to the lipid and create the
      complex. The derivatized lipid (SATA-PE) was then part of the liposome
      formulation containing DSPC:cholesterol: SATA-PE at a mole ratio of 1.5:1.0:0.26.
      SMPB-IL-2 was covalently coupled to the external surface of the SUV after
      deacetylation of the thioester moiety at pH 7.4 in PBS. Liposomes prepared by
      sonication or extrusion had an average diameter of 46-50 nm. SUV-IL-2 bound to
      the high affinity IL-2 receptor as measured by competitive binding assays and
      Scatchard analysis using 111InCl2-loaded liposomes The preparation exhibited a
      binding constant of 30 pM, consistent with values for free IL-2 cited in the
      literature. SUV IL-2 could be used as the sole source of IL-2 for the murine CTLL
      2 T-cell line or for human mitogen-activated PBLs. The presence of IL-2 coupled
      to the surface was absolutely required for delivery of the drug to the cell. When
      methotrexate was encapsulated within the internal aqueous space, receptor
      mediated endocytosis led to the inhibition of proliferation due to delivery of
      MTX to the cytoplasm of the cell. More than 90% of the methotrexate was retained
      within the liposome during storage over a 24-h period at 4 degrees C. This
      immunoliposome represents a new class of cell specific immunoliposomes whose
      entry into the cell is controlled by a cell surface receptor.

PMID- 9545573
TI  - Molecular cloning of a human cDNA for the 41-kDa phosphoribosylpyrophosphate
      synthetase-associated protein.
AB  - A human cDNA encoding 41-kDa phosphoribosylpyrophosphate (PRPP) synthetase (PRS)
      associated protein (PAP41) was cloned from two expressed sequence tag (EST)
      clones having the nucleotide similarity of 61.5 and 70.0% to human PAP39 cDNA.
      The predicted open reading frame of 1107 base pairs (bp) has the nucleotide
      identity of 91.8% to rat PAP41 and encodes a protein of 369 amino acids with a
      calculated molecular weight (MW) of 40,925. The deduced amino acid sequence
      exhibits the 98.9% identity to rat PAP41 and 72.2, 50.6, and 50.0% identity with
      human PAP39, PRS I, and PRS II, respectively, but lacks the PRPP binding site.
      Southern blot analysis suggested that the PAP41 gene exists as a single copy in
      the human genome. The single PAP41 mRNA of about 2.1 kb was shown to be present
      in five human cell lines by Northern blot analysis.

PMID- 9545574
TI  - Identification of two new members of the mouse prolactin gene family.
AB  - The prolactin (PRL) family consists of a collection of genes expressed in the
      uterus, placenta, and anterior pituitary. These cytokines/hormones participate in
      the control of maternal-fetal adaptations to pregnancy. In this report, we
      establish the presence of two new members of the mouse PRL family. Novel
      expressed sequence tags (ESTs) with significant homology to PRL were isolated
      from embryonic, ectoplacental cone, and placental cDNA libraries. The cDNAs were
      sequenced and compared to other members of the PRL family. The two new cDNAs were
      assigned to the PRL family based on sequence homology and were referred to as PRL
      like protein-F (PLP-F) and PRL-like protein-G (PLP-G). PLP-F cDNA encodes for a
      predicted 267 amino acid protein containing a 30 amino acid signal peptide and
      three putative N-linked glycosylation sites. PLP-G cDNA encodes for a predicted
      266 amino acid protein containing a 30 amino acid signal peptide and six putative
      N-linked glycosylation sites. Sequence alignments of these proteins with other
      members of the PRL family suggest some unique features. Both sequences contain an
      extra amino acid segment located between exons two and three of the prototypical
      PRL gene and a nine amino acid carboxy terminal extension. PLP-F contained an
      additional 15 amino acid region situated between exons four and five of the
      prototypical PRL gene. Both PLP-F and PLP-G mRNAs were expressed in the placenta
      but not in other tissues (uterus, brain, thymus, heart, lung, diaphragm, liver,
      kidney, and ovary). In summary, the two newly identified members share
      approximately 50% amino acid sequence identity, are specifically expressed in the
      placenta, and represent a new subfamily within the PRL family.

PMID- 9545575
TI  - Mechanism of the inhibitory effect of imipramine on the Na+-dependent transport
      of L-glutamic acid in rat intestinal brush-border membrane.
AB  - The mechanism of the inhibitory effect of imipramine, a lipophilic organic cation
      on the Na+-dependent transport of L-glutamic acid across intestinal brush-border
      membrane was investigated. The uptake of L-glutamic acid by intestinal brush
      border membrane vesicles was dependent on the concentration of Na+. Fitting of
      the uptake data in the presence of various concentrations of Na+ using Hill
      equation yielded a Hill coefficient of 2.18. This result suggest that the carrier
      system of L-glutamic acid has at least two sites for Na+-binding. By the analysis
      of double reciprocal plot and Dixon-type plot, it was found that imipramine
      inhibits the transport of L-glutamic acid by interacting competitively with the
      binding sites of Na+, but not inhibit L-glutamic acid binding site. Moreover, the
      effect of imipramine on the transport of L-alanine and D-glucose which are co
      transported with only one Na+ molecule was also suggestive of interaction with
      the Na+-binding sites on the carrier. These results indicate that the mechanism
      of the inhibitory effect of imipramine on the Na+-dependent carrier systems is
      common for all systems regardless of the stoichiometry or substrates.

PMID- 9545576
TI  - Lymphatic uptake and biodistribution of liposomes after subcutaneous injection .
      IV. Fate of liposomes in regional lymph nodes.
AB  - The ability of clodronate-containing liposomes to deplete lymph nodes of
      macrophages was used as a tool to investigate the fate of liposomes in regional
      lymph nodes after subcutaneous (s.c.) administration. Reduced lymph node
      localization of liposomes in macrophage-depleted lymph nodes confirmed that
      phagocytosis by macrophages plays an important role in lymph node retention of
      liposomes. Depletion of macrophages had less effect on lymph node localization of
      small liposomes than on the lymph node localization of large liposomes. Inclusion
      of distearoylphosphatidylethanolamine (DSPE)-poly(ethyleneglycol) (PEG-PE) into
      the liposomes, which is known to oppose macrophage uptake, did not affect lymph
      node localization in macrophage-depleted or control lymph nodes. We conclude that
      PEG-liposomes retained by lymph nodes are also taken up by lymph node
      macrophages. Morphological observations visualizing the uptake of PEG-liposomes
      by lymph node macrophages support this conclusion.

PMID- 9545577
TI  - Cloning of the cDNA encoding rat presenilin-2.
AB  - We report here the cDNA sequence of rat homologue of presenilin-2 (PS-2). The rat
      PS-2 cDNA encoded 448 amino acids, and the deduced amino acid sequence was highly
      homologous to those of the human (94.9%), mouse (96.4%) and Xenopus (70.8%). A
      minor splicing variant lacking a single glutamate was detected, while the product
      corresponding to the exon 9 deleted splicing variant observed in human was not
      detected.

PMID- 9545578
TI  - Cloning of chicken and mouse alpha 1b adrenergic receptor.
AB  - A partial cDNA encoding most of the third intracellular loop of the chicken alpha
      1b adrenergic receptor subtype, obtained by reverse transcription-polymerase
      chain reaction (RT-PCR) techniques using degenerate primers derived from
      mammalian sequences, was used to isolate an alpha 1b adrenergic receptor cDNA
      from brain. The cDNA encodes a potential protein of 507 amino acids and Northern
      hybridization of poly(A)+ RNA from chicken brain of different developmental
      stages detected a single 3.5 kb transcript. Analysis of receptor expression
      indicated that the alpha 1b adrenergic receptor is widely distributed in chicken
      tissues, specially kidney and liver. cDNA and genomic clones encoding sequences
      of the mouse alpha 1b adrenergic receptor were also isolated.

PMID- 9545579
TI  - Characterization of the 5' flanking region of the human NPT-1 Na+/phosphate
      cotransporter gene.
AB  - To elucidate the expression and regulation of the human type I Na+/phosphate
      transporter gene (NPT-1), the 5' flanking region of the NPT-1 gene was cloned,
      and its nucleotide sequence and function were determined. A genomic clone that
      contained approximately 14.0 kb of the 5'-flanking region of the NPT-1 gene was
      isolated. A single transcription start site was located 104 base pairs (bp)
      upstream of the 3' end of exon 1. In addition to the sequence of the 5'-flanking
      region contained a sequence weakly homologous to a TATA box at position -41 to 
      36 and many transcriptional regulatory elements. Transient expression revealed
      that a 45-bp region of proximal to exon 1, which contained TATA-like sequence,
      was sufficient for promoting luciferase expression in OK-cells derived from
      opossum kidney proximal tubule.

PMID- 9545580
TI  - Isolation of cDNA encoding a novel human CC chemokine NCC-4/LEC.
AB  - We have determined the entire sequence of human cDNA encoding a novel CC
      chemokine NCC-4 by 5' and 3' RACE methods. Two types of transcripts, 579 bp and
      1503 bp long, respectively, are generated through alternative polyadenylation
      sites. Both species contain an open reading frame encoding 120 amino acids with
      19-38% identity to other human CC chemokines. The short and long transcripts are
      expressed highly selectively in the liver at nearly equivalent levels. There
      seems to be one copy of the gene per haploid genome. We now designate NCC-4 as
      LEC from liver-expressed chemokine.

PMID- 9545581
TI  - Palmitic acid is associated with halorhodopsin as a free fatty acid.
      Radiolabeling of halorhodopsin with 3H-palmitic acid and chemical analysis of the
      reaction products of purified halorhodopsin with thiols and NaBH4.
AB  - Halorhodopsin, isolated from Halobacterium salinarium cells incubated with
      tritiated palmitic acid, co-elutes with labeled palmitate in phenylsepharose CL
      4B chromatography. Halorhodopsin-bound 3H-palmitate is not readily displaced by
      prolonged exposure to a large excess of detergents and by re-chromatography of
      radiolabeled halorhodopsin on phenylsepharose. On other hand, the association of
      labeled palmitate with purified halorhodopsin is not resistant to denaturation
      induced either by isopropanol/hexane or by SDS gel electrophoresis. We have
      tested the hypothesis that tightly associated palmitate is bound to halorhodopsin
      through a thioester bond, which is unstable in denaturing conditions. Using
      GC/MS, we have analysed the reaction products of native halorhodopsin with
      specific thioester reagents, thiols and NaBH4, which are inactive on free fatty
      acids. The results of this analytical approach indicate that there is no
      thioester bond between halorhodopsin and palmitic acid and that palmitic acid is
      associated with halorhodopsin as a free fatty acid.

PMID- 9545582
TI  - Analysis of expression of the gene encoding for the nuclear autoantigen La/SS-B
      using reporter gene constructs.
AB  - In earlier studies mRNA isoforms encoding for the nuclear autoantigen La were
      identified. In an alternative La mRNA form the exon 1 was replaced with the exon
      1'. Moreover, exon 1' La mRNAs were found to start at different 5'-regions. In
      dependence on the 5'-start the exon 1' La mRNAs encoded for up to three open
      reading frames upstream of the La frame, which starts in the exon 2. The exon 1'
      was located in the intron about 70 nts downstream of the exon 1. The exon 1' La
      mRNA was proposed to be the result of a promoter switch in combination with an
      alternative splicing mechanism. The commonly used technique to study the
      expression of a eucaryotic gene is to fuse a reportergene immediately downstream
      of the proposed regulatory elements. Due to (i) the short distance between exon 1
      and exon 1', (ii) the varying 5'-starts of the exon 1' La mRNAs, and (iii) the
      upstream open reading frames in the exon 1' La mRNAs this technique appeared to
      be difficult to apply to the La gene. In order to overcome these problems a
      luciferase reportergene construct was cloned which started about 2500 nts
      upstream of the exon 1 and contained the exon 1, the intron including the exon
      1', and a portion of the exon 2. Luciferase was fused into the exon 2. This
      construct was used to prepare 5'-deletion mutants. The constructs were
      transiently transfected into HeLa cells. RNAs were isolated from the transiently
      transfected cells and analyzed using the 5'-Rapid Amplification of cDNA End
      technique. The PCR products were subcloned and sequenced. This analysis showed
      that exon 1 and exon 1' transcripts were correctly transcribed and spliced from
      the La luciferase fusion construct. Moreover, the 5'-start of the respective
      transcript allowed to identify those genomic regions in the La gene that were
      most likely being involved in determining the respective transcription initiation
      site. In parallel to the estimation of the 5'-start of the transcripts, the
      luciferase activity was measured. Thereby we detected a cryptic promoter element
      in the intron between the exon 1 and exon 2.

PMID- 9545583
TI  - Self-assembled alpha-hemolysin pores in an S-layer-supported lipid bilayer.
AB  - The effects of a supporting proteinaceous surface-layer (S-layer) from Bacillus
      coagulans E38-66 on a 1,2-diphytanoyl-sn-glycero-3-phosphatidylcholine (DPhPC)
      bilayer were investigated. Comparative voltage clamp studies on plain and S-layer
      supported DPhPC bilayers revealed no significant difference in the capacitance.
      The conductance of the composite membrane decreased slightly upon
      recrystallization of the S-layer. Thus, the attached S-layer lattice did not
      interpenetrate or rupture the DPhPC bilayer. The self-assembly of a pore-forming
      protein into the S-layer supported lipid bilayer was examined. Staphylococcal
      alpha-hemolysin formed lytic pores when added to the lipid-exposed side. The
      assembly was slow compared to unsupported membranes, perhaps due to an altered
      fluidity of the lipid bilayer. No assembly could be detected upon adding alpha
      hemolysin monomers to the S-layer-faced side of the composite membrane.
      Therefore, the intrinsic molecular sieving properties of the S-layer lattice do
      not allow passage of alpha-hemolysin monomers through the S-layer pores to the
      lipid bilayer. In comparison to plain lipid bilayers, the S-layer supported lipid
      membrane had a decreased tendency to rupture in the presence of alpha-hemolysin.

PMID- 9545584
TI  - Successful recovery of the normal electrophysiological properties of PorB (class
      3) porin from Neisseria meningitidis after expression in Escherichia coli and
      renaturation.
AB  - Neisseria meningitidis PorB class 3 porins obtained either from native membranes
      (wild-type) or recovered from inclusion bodies following expression in
      Escherichia coli (recombinant), have been reconstituted into solvent-free planar
      phospholipid membranes. The wild-type and recombinant porins exhibited the same
      single-trimer conductance (1-1.3 nS in 200 mM NaCl), tri-level closure pattern,
      characteristic of functional channel trimers, and pattern of insertion into
      planar membranes. Both proteins were open at low voltages and displayed two
      voltage-dependent closure processes, one at positive and the other at negative
      potentials. Both showed asymmetric voltage dependence such that one gating
      process occurred at lower voltages (Vo=15 mV) than the other (Vo=25 mV). The sign
      of the potential that resulted in closure at low voltages varied from membrane to
      membrane indicating that they may have the property of auto-directed insertion
      (in analogy to the mitochondrial channel, VDAC). In the case of the recombinant
      porin, the steepness of the voltage dependence of one gating process was slightly
      less (n=1.3) than that observed for the other process or for the wild-type
      channel (n=1.5-1.7). Both channels have a high (40%) probability of closure even
      at 0 mV. While both channels show a slight selectivity for Cl- over Na+, the
      selectivity of the recombinant porin is a bit higher (permeability ratio of 2.8
      vs. 1.6) as measured using a 2-fold salt gradient. Thus, the method employed to
      refold the recombinant porin was successful in not only restoring wild-type
      structure [H.L. Qi, J.Y. Tai, M.S. Blake, Expression of large amounts of
      Neisserial porin proteins in Escherichia coli and refolding of the proteins into
      native trimers, Infect. Immun. 62 (1994) 2432-2439; C.A.S.A. Minetti, J.Y. Tai,
      M.S. Blake, J.K. Pullen, S.M. Liang, D.P. Remeta, Structural and functional
      characterization of a recombinant PorB class 2 protein from Neisseria
      meningitidis. Conformational stability and porin activity, J. Biol. Chem. 272
      (1997) 10710-10720] but also the overall electrophysiological function.

PMID- 9545585
TI  - Gene expression of mouse M1 and M2 pyruvate kinase isoenzymes correlates with
      differential poly[A] tract extension of their mRNAs during the development of
      spermatogenesis.
AB  - In eukaryotes, different isoenzymes for pyruvate kinase have been characterized.
      M2-type Pk cDNA from a mouse fetal ovary library was isolated and differential
      expression for M1 and M2-types during testis development was observed. While the
      presence of M2 mRNAs decreases throughout the development of spermatogenesis, we
      deduced that M1 type expression increases in adult testis coinciding with the
      presence of elongating spermatids in the seminiferous epithelium. Polyadenylation
      tests showed a concurrent increase in the length of the polyadenylation tail of
      transcribed M1-type pyruvate kinase mRNAs in prepuberal to adult seminiferous
      tubules. A similar relationship between poly[A] tail extension and differential
      increase of gene expression was detected for M1-type mRNA in adult brain and
      muscle. Length of poly[A] tail of M2-type transcripts is shown to decrease during
      the development of mouse testis. These results suggest that changes in the length
      of the poly[A] tail of transcripts are associated with differential expression of
      both regulated isoenzymes during testicular development.

PMID- 9545587
TI  - Temperature-responsive size-exclusion chromatography using poly(N
      isopropylacrylamide) grafted silica.
AB  - Silica-based packing materials induce non-specific interactions with proteins in
      aqueous media because of the nature of their surface, mainly silanol groups.
      Therefore, the silica surface has to be modified in order to be used as
      stationary phase for the High Performance Size-Exclusion Chromatography (HPSEC)
      of proteins. For this purpose, porous silica beads were coated with hydrophilic
      polymer gels (dextrans of different molecular weights) carrying a calculated
      amount of diethyl-aminoethyl groups (DEAE). Actually, as shown by HPSEC, these
      dextran modified supports minimize non-specific adsorption for proteins and
      pullulans in aqueous solution. Then, in order to change the pore size in response
      to temperature, temperature responsive polymer of poly(N-isopropylacrylamide)
      (PIPAAm) was introduced into the surface of dextran-DEAE on porous silica beads.
      The structure of these supports before and after modification was alternately
      studied by Scanning Electronic Microscopy (SEM) and Scanning Force Microscopy
      (SFM). An adsorption of radiolabelled albumin was performed to complete our
      study. Silica modifications by dextran-DEAE and PIPAAm improve the neutrality of
      the support and minimize the non-specific interactions between the solid support
      and proteins in solution. At low temperature, the support having PIPAAm exhibits
      a high resolution domain in HPSEC and finally permits a better resolution of
      proteins and pullulans. At higher temperature, hydrophobic properties of PIPAAm
      produce interactions with some proteins and trigger off a slight delay of their
      elution time.

PMID- 9545588
TI  - Functional expression of a mammalian acetylcholinesterase in Pichia pastoris:
      comparison to acetylcholinesterase, expressed and reconstituted from Escherichia
      coli.
AB  - The mature rat brain acetylcholinesterase gene (T subunit, AChE) was subcloned
      downstream of the temperature-inducible lambda promoter PL and fused to the
      signal peptide of the OmpA protein. Three different expression vectors were
      constructed: (i) pCompmA containing the mature AChE, (ii) pComp delta TA
      containing a truncated AChE and (iii) pComp delta TAH containing the truncated
      AChE C-terminal fused to a 6xHis-tag. With all expression vectors the
      overexpression of AChE in Escherichia coli resulted mainly in cytoplasmic
      inclusion bodies (IB). However, some activity was found in the periplasmic space.
      The inclusion bodies were refolded in vitro, yielding up to 1.42 U/mg IB of
      active AChE. The refolded AChE was partially purified (approx. 300-fold) by
      affinity chromatography with a specific activity of approx. 250 U/mg. Removing
      the cysteine residue near the C-terminus (truncated AChE, delta TAChE) assuming
      to affect the refolding, did not increase the amount of active enzyme obtained
      after refolding. Purification of denatured delta TAChE-6xHis prior to refolding
      by Ni-NTA-chromatography increased the refolding efficiency by a factor of 1.5.
      Functional expression and secretion of rat brain acetylcholinesterase into the
      medium was achieved in Pichia pastoris. By optimizing the culture conditions, 100
      mU/ml AChE in the medium was produced. In this work we are describing the
      functional expression of a mammalian AChE in a microbial host in good yields for
      the first time. The physico-chemical properties of both, the bacterial and yeast
      expressed AChE were compared with those of the native AChE. The properties of the
      yeast expressed AChE and the native AChE were similar, whereas the E. coli
      expressed enzyme was found to be less stable and had different inhibition
      properties.

PMID- 9545586
TI  - Where does cholesterol act during activation of the nicotinic acetylcholine
      receptor?
AB  - Why agonist-induced activation of the nicotinic acetylcholine receptor (nAcChoR)
      fails completely in the absence of cholesterol is unknown. Affinity-purified
      nAcChoRs from Torpedo reconstituted into 1,2-dioleoyl-sn-glycero-3
      phosphatidylcholine/1, 2-dioleoyl-sn-glycero-3-phosphate/steroid bilayers at mole
      ratios of 58:12:30 were used to distinguish between three regions of the membrane
      where cholesterol might act: the lipid bilayer, the lipid-protein interface, or
      sites within the protein itself. In the bilayer, the role of fluidity has been
      ruled out and certain neutral lipids can substitute for cholesterol [C. Sunshine,
      M.G. McNamee, Biochim. Biophys. Acta 1191 (1994) 59-64]; therefore, we first
      tested the hypothesis that flip-flop of cholesterol across the membrane is
      important; a plausible mechanism might be the relief of mechanical bending strain
      induced by a conformation change that expands the two leaflets of the bilayer
      asymmetrically. Cholesterol analogs prevented from flipping by charged groups
      attached to the 3-position's hydroxyl supported channel opening, contrary to this
      hypothesis. The second hypothesis is that interstitial cholesterol binding sites
      exist deep within the nAcChoR that must be occupied for channel opening to occur.
      When cholesterol hemisuccinate was covalently 'tethered' to the glycerol backbone
      of phosphatidylcholine, channel opening was still supported. Thus, if there are
      functionally important cholesterol sites, they must be very close to the lipid
      protein interface and might be termed periannular.

PMID- 9545589
TI  - In vivo activation of yeast plasma membrane H+-ATPase by ethanol: effect on the
      kinetic parameters and involvement of the carboxyl-terminus regulatory domain.
AB  - The in vivo activation of Saccharomyces cerevisiae plasma membrane H+-ATPase by
      ethanol was observed during ethanol-stressed cultivation or following the rapid
      incubation of cells with ethanol (6% (v/v)). Ethanol activated both the basal and
      the glucose-activated forms of the enzyme being the H+-ATPase fully activated by
      glucose (5% (w/v)) still additionally activable by ethanol. The kinetic
      parameters of ethanol-activated and non-activated H+-ATPase were calculated based
      directly on Michaelis-Menten equation (with MgATP concentrations in the range 0.
      16-8.18 mM and 7.5 mM of free Mg2+); the rectangular hyperbolic function was
      solved using iterative procedures. Ethanol-induced stimulation of plasma membrane
      H+-ATPase activity was associated to the increase of Vmax whereas the Km for
      MgATP increased. Results obtained with mutants constructed and used in previous
      studies envisaging the analysis of the molecular mechanisms underlying plasma
      membrane ATPase activation by glucose, external acidification and nitrogen
      starvation, suggested that the carboxyl-terminus (C-terminus) regulatory domain
      may also be involved in the in vivo activation by ethanol.

PMID- 9545590
TI  - The effect of ethanol on pancreatic enzymes--a dietary artefact?
AB  - The effects of ethanol on pancreatic digestive and lysosomal enzymes may be
      relevant to the pathogenesis of alcoholic pancreatitis since pancreatic enzymes
      are thought to play an important role in the development of pancreatic injury.
      Previous studies, using the Lieber-DeCarli pair-feeding model of ethanol
      administration, have demonstrated that ethanol significantly increases the
      content and gene expression of pancreatic enzymes. However, these findings have
      been questioned because, in the Lieber-DeCarli model, ethanol-fed rats have a
      lower carbohydrate intake than their pair-fed controls, making it difficult to
      ascribe any observed changes to ethanol alone. This study was designed to
      distinguish between the effects of ethanol and those of reduced dietary
      carbohydrate on pancreatic enzymes, using a quartet-feeding model of ethanol
      administration. Rats were fed liquid diets containing low (11%) and high (47%)
      amounts of carbohydrate, with and without ethanol, for four weeks. The effects of
      ethanol on pancreatic content and messenger RNA levels for digestive enzymes
      (trypsinogen, chymotrypsinogen and lipase) and a lysosomal enzyme (cathepsin B)
      were assessed. Ethanol feeding resulted in a significant increase in glandular
      content with a corresponding increase in mRNA levels for all four enzymes
      studied. By contrast, a reduction in dietary carbohydrate intake alone did not
      alter pancreatic content or gene expression for the above enzymes. These results
      indicate that (i) ethanol significantly increases the capacity of the acinar
      cells to synthesise digestive enzymes and the lysosomal enzyme cathepsin B, and
      (ii) these changes are due to ethanol itself and are not due to variations in
      dietary carbohydrate intake.

PMID- 9545591
TI  - Verapamil enhances the uptake and the photocytotoxic effect of PII, but not that
      of tetra(4-sulfonatophenyl)porphine.
AB  - The influence of the calcium channel blocker verapamil on the sensitivity of
      mouse fibrosarcoma cells of the line EMT-6 to treatment with Photofrin II (PII)
      or tetra(4-sulfonatophenyl)porphine (TPPS4) and light has been assessed. Cells
      were treated with 1.5 microg/ml PII or 75 microg/ml TPPS4 overnight in the
      absence or presence of 50 microg/ml verapamil and subsequently exposed to light.
      Verapamil increased the sensitivity of the EMT-6 cells to PII-induced
      photoinactivation by a factor of 2. In contrast, verapamil decreased the
      sensitivity of the cells to TPPS4-induced photoinactivation by 50-60%. Both
      sensitizers were found to be located to a large extent in lysosomes as revealed
      by fluorescence microscopy and by photochemical inactivation of the lysosomal
      marker enzyme beta-N-acetyl-D-glucosaminidase. Verapamil increased the uptake of
      PII by 30% and reduced the uptake of TPPS4 by 20%. Furthermore, verapamil
      enhanced the binding and uptake of LDL by about 40%. In conclusion, the effects
      of verapamil-induced sensitization of EMT-6 cells treated with PII or TPPS4 and
      light can to a large extent be attributed to the modulatory effects of verapamil
      on endocytosis.

PMID- 9545592
TI  - IGF-1, PDGF and CD18 are adherence-responsive genes: regulation during monocyte
      differentiation.
AB  - Unstimulated mononuclear cells express IGF-1, PDGF-A and PDGF-B mRNA, but not a
      number of other genes coding for growth factors or cytokines, as we demonstrated
      previously. The main focus of the present investigation was to compare gene
      expression of mononuclear cells unstimulated in suspension with gene expression
      of monocytes stimulated by adherence. mRNA levels of IGF-1-A and -B, PDGF-A, -B,
      PD-ECGF, basic FGF, acidic FGF, TGF-alpha, TGF-beta 1, and IGF-2 were sought for
      and quantified with our sensitive RT-PCR method (3n-PCR). The respective mRNAs of
      basic FGF, acidic FGF, TGF-alpha and IGF-2 were not detected, independent of the
      culture conditions. In suspension culture, mRNA levels of IGF-1A and -B, PDGF-A, 
      B, and CD18 remained unchanged. Monocyte adherence regulated IGF-1A, PDGF-A, and 
      B mRNA levels. In parallel, mRNA levels of the monocyte adhesion molecule CD18
      increased rapidly (4.5-fold). In contrast, independent of the presence of an
      adherence stimulus, the mRNAs for the cytoskeletal structure protein beta-actin
      and PD-ECGF remained constant, whereas mRNA for growth factors TGF-beta 1 and IGF
      1B, respectively, was increased. Thus, monocyte adherence selectively regulates
      IGF-1, PDGF-A, PDGF-B and CD18 mRNAs (adherence-responsive genes) in a
      coordinated manner. This led us to identify two novel consensus elements within
      their respective functional promoters. Both motifs, an 11 bp purine-rich sequence
      and a 13 bp pyrimidine-rich segment, respectively, are absent from the genes that
      were not specifically activated by adherence. The identified elements are
      potential binding sites for transcription factors that may define a common basis
      for the regulation of the adherence-responsive genes IGF-1A, PDGF-A, PDGF-B and
      CD18.

PMID- 9545593
TI  - Oligomerization of beta-dystroglycan in rabbit diaphragm and brain as revealed by
      chemical crosslinking.
AB  - The surface component beta-dystroglycan is a member of the dystrophin
      glycoprotein complex providing a trans-sarcolemmal linkage between the actin
      membrane cytoskeleton and the extracellular matrix component laminin-alpha2.
      Although abnormalities in this complex are involved in the pathophysiology of
      various neuromuscular disorders, little is known about the organization of
      dystrophin-associated glycoproteins in diaphragm and brain. We therefore
      investigated the oligomerization of beta-dystroglycan and its connection with the
      most abundant dystrophin homologues in these two tissues. Employing detergent
      solubilization and alkaline extraction procedures of native membranes, it was
      confirmed that beta-dystroglycan behaves like an integral surface molecule as
      predicted by its cDNA sequence. Immunoblot analysis following chemical
      crosslinking of native membranes showed that beta-dystroglycan has a tendency to
      form high-molecular-mass complexes. Within these crosslinkable complexes, immuno
      reactive overlaps were observed between beta-dystroglycan, alpha-dystroglycan,
      laminin and 427 kDa dystrophin in diaphragm and skeletal muscle. In synaptosomes,
      the major brain dystrophin isoform Dp116 also exhibited an immuno-reactive
      overlap with members of the dystroglycan complex. These findings demonstrate that
      beta-dystroglycan does not exist as a monomer in native membranes and imply that
      certain dystrophin isoforms and dystrophin-associated components interact with
      this surface protein in diaphragm and brain as has been previously shown for
      skeletal and heart muscle.

PMID- 9545594
TI  - Effects of the sulforaphane analog compound 30, indole-3-carbinol, D-limonene or
      relafen on glutathione S-transferases and glutathione peroxidase of the rat
      digestive tract.
AB  - Several dietary compounds have been demonstrated to reduce gastrointestinal
      cancer rates in both humans and animals. We showed that high human
      gastrointestinal tissue levels of glutathione S-transferase (GST), a family of
      detoxification enzymes consisting of class Alpha, Mu, Pi and Theta isoforms, were
      inversely correlated with cancer risk. We now investigated whether the
      sulforaphane analog compound 30, indole-3-carbinol, D-limonene or relafen,
      supplemented in the diet for two weeks at 1450, 250, 10,000, and 200 ppm,
      respectively, influenced (i) GST activity, (ii) GST isoenzyme levels, (iii) GSH
      levels, or (iv) glutathione peroxidase (GPx) activity in the gastrointestinal
      tract of male Wistar rats. Sulforaphane analog compound 30 enhanced GST activity
      in all organs studied (1.2-2.4 x). It induced GST Alpha levels in small intestine
      and liver, GST Mu levels in stomach and small intestine, GST Pi levels in stomach
      and small and large intestine, and GSH levels in stomach and proximal and middle
      small intestine. Indole-3-carbinol induced gastric GST Mu and hepatic GST Alpha
      levels. D-limonene induced hepatic GST Alpha, colonic GST Pi levels and proximal
      small intestinal GST enzyme activity and GST Pi levels. Relafen induced hepatic
      GST Alpha levels, distal small intestinal and gastric GST Pi levels, and
      oesophageal and proximal small intestinal GSH levels. GPx activity was enhanced
      by relafen in oesophagus, and in distal small intestine by sulforaphane analog
      compound 30. Enhancement of GSTs and to a lesser extent GPx and GSH, resulting in
      a more efficient detoxification, may explain at least in part the
      anticarcinogenic properties of sulforaphane analog compound 30, and to a much
      lesser extent of indole-3-carbinol and D-limonene.

PMID- 9545595
TI  - Structure of the human Nkx2.1 gene.
AB  - NKX2.1 is a member of the NK2 family of homeodomain-containing transcriptional
      factors which binds to and activates the promoters of thyroid and pulmonary
      epithelial genes. We have cloned and sequenced twelve human lung NKx2.1 cDNAs. To
      elucidate the origin of Nkx2.1 transcripts, we also cloned and sequenced a 12 kb
      human Nkx2.1 genomic clone. Alignment of cDNA sequences with the genomic clone
      showed that contrary to previous reports, the human Nkx2.1 gene is organized into
      three exons and two introns. The newly discovered exon I contains an ATG codon
      that falls in frame with the previously identified Nkx2.1 initiator ATG codon on
      one of the cDNAs, designated 5E. Northern blot analysis shows that an mRNA of
      approximately 2.5 kb in size, homologous to 5E, is expressed in both lung and
      thyroid. The deduced amino acid sequence of the longest open reading frame on 5E
      is identical to NKX2.1 with the exception of a 30 amino acid N-terminal
      extension. Coupled in vitro transcription/translation of the 5E cDNA confirms
      that the open reading frame is translated into a contiguous polypeptide of 44
      kDa. Analysis of Nkx2.1 genomic DNA fragments suggest that at least two
      independent regions, one within the first intron and the other 5' of the first
      exon may mediate the basal promoter activity of the Nkx2.1 gene in lung
      epithelial cells.

PMID- 9545597
TI  - Control analysis of metabolic systems involving quasi-equilibrium reactions.
AB  - Reactions for which the rates are extremely sensitive to changes in the
      concentrations of variable metabolite concentrations contribute little to the
      control of biochemical reaction networks. Yet they do interfere with the
      calculation of the system's behaviour, both in terms of numerical integration of
      the rate equations and in terms of the analysis of metabolic control. We here
      present a way to solve this problem systematically for systems with time
      hierarchies. We identify the fast reactions and fast metabolites, group them
      apart from the other ("slow") reactions and metabolites, and then apply the
      appropriate quasi-equilibrium condition for the fast subsystem. This then makes
      it possible to eliminate the fast reactions and their elasticity coefficients
      from the calculations, allowing the calculation of the control coefficients of
      the slow reactions in terms of the elasticity coefficients of the slow reactions.
      As expected, the elasticity coefficients of the fast reactions drop out of the
      calculations, and they are irrelevant for control at the time resolution of the
      steady state of the slow reactions. The analysis, when applied iteratively, is
      expected to be particularly valuable for the control analysis of living cells,
      where a time hierarchy exists, the fastest being at the level of enzyme kinetics
      and the slowest at gene expression.

PMID- 9545596
TI  - Molybdate binding by ModA, the periplasmic component of the Escherichia coli mod
      molybdate transport system.
AB  - ModA, the periplasmic-binding protein of the Escherichia coli mod transport
      system was overexpressed and purified. Binding of molybdate and tungstate to ModA
      was found to modify the UV absorption and fluorescence emission spectra of the
      protein. Titration of these changes showed that ModA binds molybdate and
      tungstate in a 1:1 molar ratio. ModA showed an intrinsic fluorescence emission
      spectrum attributable to its three tryptophanyl residues. Molybdate binding
      caused a conformational change in the protein characterized by: (i) a shift of
      tryptophanyl groups to a more hydrophobic environment; (ii) a quenching (at pH
      5.0) or enhancement (at pH 7.8) of fluorescence; and (iii) a higher availability
      of tryptophanyl groups to the polar quencher acrylamide. The tight binding of
      molybdate did not allow an accurate estimation of the binding constants by these
      indirect methods. An isotopic binding method with 99MoO42- was used for accurate
      determination of KD (20 nM) and stoichiometry (1:1 molar ratio). ModA bound
      tungstate with approximately the same affinity, but did not bind sulfate or
      phosphate. These KDs are 150- to 250-fold lower than those previously reported,
      and compatible with the high molybdate transport affinity of the mod system. The
      affinity of ModA for molybdate was also determined in vivo and found to be
      similar to that determined in vitro.

PMID- 9545598
TI  - Kinetics of lactone hydrolysis in antitumor drugs of camptothecin series as
      studied by fluorescence spectroscopy.
AB  - Potent antitumor activity exhibited by 20-S-camptothecin (CPT) and numerous
      derivatives is known to be lost upon opening of the alpha-hydroxy-lactone ring of
      these drugs, hydrolyzable at neutral and basic pH. To quantify in 'real time' the
      lactone hydrolysis reaction in CPTs under physiological conditions, we have
      applied a non-perturbing approach by fluorescence spectroscopy. CPT and a set of
      its derivatives (21-lactam-S-CPT, 10,11-(methylenedioxy)-CPT, CPT-11, SN-38,
      topotecan, tricyclic ketone-CPT) with antitumor activity varying from negligible
      to 10 times that of CPT have been studied. Prior to the kinetic measurements, the
      effects of substitutions, pH, polarity of molecular environment, lactone ring
      opening (lactone-carboxylate transition) have been investigated in terms of the
      UV-visible absorption and fluorescence emission spectra of CPTs. Then the
      determined parameters of the fluorescence emission spectra corresponding to the
      respective lactone and carboxylate forms have been used to estimate the residual
      lactone percentage as a function of time. The reproducibility of the obtained
      data demonstrates that the spectroscopic approach provides a satisfactory
      precision for this kind of measurements. For CPT at pH 7.3, the lactone half-life
      was 29.4 +/- 1.7 min and the lactone percentage at equilibrium was 20.9 +/- 0.3%.
      Within a series of derivatives with substitutions at quinoline rings, the lactone
      half-life varied from 29 to 32 min and the equilibrium lactone content varied
      from 15% to 23%. For each compound, even slight increase of pH from 7.1 to 7.3 or
      from 7.3 to 7.6 logically leads to a remarkable decrease of both lactone half
      life and equilibrium lactone percentage.

PMID- 9545599
TI  - High resolution 1H NMR spectroscopic studies on dynamic biochemical processes in
      incubated human seminal fluid samples.
AB  - High resolution 600 MHz 1H NMR spectroscopy was used to investigate the changes
      in biochemical composition of whole human seminal fluid (SF) and an artificial
      mixture of prostatic (PF) and seminal vesicle fluid (SVF). A variety of time
      related biochemical changes were monitored simultaneously and non-invasively in
      SF, including enzymatic hydrolysis of phosphorylcholine to choline and
      polypeptides to amino acids. The fastest NMR-observable reactions in SF were the
      conversion of phosphorylcholine to choline (t1/2 approximately equal to 9 min)
      and uridine-5'-monophosphate (UMP) to uridine (t1/2 < 2 min). UMP has not
      previously been detected in SF because of its rapid hydrolysis. Artificial
      mixtures of separately obtained prostatic and SVF showed very similar biochemical
      changes to those observed in whole SF. Addition of EDTA to SF incubated for 2 min
      post ejaculation strongly inhibited peptide hydrolysis. Zn2+, present in whole SF
      was shown to be non EDTA-chelatable 2 min after ejaculation, whereas after 7 min,
      a singlet signal from the ethylenic protons of the Zn-EDTA2- complex was clearly
      observed which remained constant after 7 min. This indicates that soon after
      ejaculation (< 5 min) Zn2+ is immobilised in a macromolecular complex which is
      rapidly broken down by proteolytic enzymes, the released Zn2+ then being free to
      react with EDTA. Mg- and Ca-EDTA2- complexes were observed at 2 min and remained
      constant (at 1.4 and 2.1 mM, respectively) throughout the entire time course of
      the experiment. These studies cast new light on the time-related biochemical
      changes occurring in the post-ejaculatory SF which may have an important role in
      reproductive function.

PMID- 9545600
TI  - Electrochemical analysis of the interactions of laccase mediators with lignin
      model compounds.
AB  - The mechanism of oxidation of lignin by laccase and mediator has been
      investigated by cyclic voltammetry and bulk electrolysis. Electrochemical
      properties and reactivities of the two mediators 2,2'-azinobis-(3
      ethylbenzthiazoline-6-sulfonate) (ABTS) and 1-hydroxybenzotriazole (HBT) were
      studied and their intermediates responsible for lignin oxidation were
      characterized. ABTS was oxidized first to the cation radical (ABTS+.) and then to
      the dication (ABTS2+). The two oxidized species are relatively stable and
      electrochemically reversible, with formal redox potentials (E0' vs Ag/AgCl) of
      472 mV for ABTS/ABTS+. and 885 mV for ABTS+./ABTS2+. The dication was shown to be
      the intermediate responsible for the oxidation of the non-phenolic lignin model
      compound veratryl alcohol, whereas the cation radical reacted only with phenolic
      structures in lignin. Cyclic voltammetry of HBT shows only one oxidation peak at
      878 mV, but unlike ABTS, the oxidized intermediate was not stable and decayed
      rapidly. The radical intermediate of HBT was shown to catalyze the oxidation of
      veratryl alcohol to veratraldehyde. The kinetics of homogeneous redox catalysis
      of mediators and veratryl alcohol were estimated. ABTS-mediated lignin oxidation
      at the redox potential of laccase (585 mV) was shown to be possible, but at a
      very slow rate, as previously reported for laccase and mediator.

PMID- 9545601
TI  - 2-Methoxy-4-nitroaniline and its isomers induce cytochrome P4501A (CYP1A) enzymes
      with different selectivities in the rat liver.
AB  - We reported previously that 2-methoxy-4-nitroaniline (2-MeO-4-NA) is a selective
      inducer of cytochrome P4501A2 (CYP1A2) in the rat liver, and its molecular size
      is the smallest among known CYP1A2-selective inducers. In the present study, a
      structure-activity relationship on the CYP1A2-selective induction has been
      investigated using isomeric nitroanisidines and their related chemicals. Western
      blot analyses revealed that the chemicals removed a substituent (amino, methoxyl
      or nitro group) from a 2-MeO-4-NA molecule had no capacity for inducing CYP1A
      enzymes in rat livers. On the other hand, isomeric nitroanisidines such as 2-MeO
      4-NA, 2-MeO-5-NA and 4-MeO-2-NA induced both CYP1A2 and CYP1A1 enzymes with
      different selectivities. As judged from the induced levels of CYP1A proteins, 2
      MeO-4-NA (CYP1A2/CYP1A1 ratio; 9.5) and 4-MeO-2-NA (0.3) were the most selective
      inducers of CYP1A2 and CYP1A1, respectively, among the isomeric nitroanisidines
      (0.44 mmol/kg) used. The induced level of CYP1A2 protein was in the order 2-MeO-4
      NA > 2-MeO-5-NA > 4-MeO-2-NA, although no significant difference was observed on
      their CYP1A2 mRNA level. On the contrary, increases in the levels of CYP1A1 mRNA
      and protein were in the order 4-MeO-2-NA > 2-MeO-5-NA > 2-MeO-4-NA. The present
      findings indicate that all three substituents (amino, methoxyl and nitro groups)
      are necessary components of nitroanisidines for induction of CYP1A enzymes, and
      also show that regio-isomeric positions of these substituents determine the
      selectivity in the induction of CYP1A enzymes.

PMID- 9545602
TI  - Peroxisomal localization of D-aspartate oxidase and development of peroxisomes in
      the yeast Cryptococcus humicolus UJ1 grown on D-aspartate.
AB  - The peroxisomal localization of D-aspartate oxidase (EC. 1.4.3.1) was
      demonstrated in the yeast Cryptococcus humicolus UJ1 cells grown in the medium
      containing D-aspartate as a nitrogen source. The conclusion is based on the
      identical behavior of the enzyme with those of peroxisomal marker enzymes,
      catalase and urate oxidase, during all steps of subcellular fractionations.
      Supporting evidence was provided by the morphometric analysis of the peroxisomes
      with electron microscopy, showing that the cells grown on D-aspartate contained
      more and larger peroxisomes than those grown on L-aspartate, consistent with the
      500-fold and 3-fold, higher contents of D-aspartate oxidase and catalase
      activities, respectively, in the former cells than the latter.

PMID- 9545603
TI  - The Web, communication trends, and children's health. Part 1: Development and
      technology of the Internet and Web.
AB  - The Internet and The World Wide Web are changing the way pediatricians find
      medical information and provide care. This article, the first in a four-part
      series on The Web, Communication Trends, and Children's Health, published in
      consecutive issues of this journal, describes how the Web was created and how its
      multimedia capabilities are affecting information exchange.

PMID- 9545605
TI  - Lack of evidence of transmission of HIV-1 to family contacts of HIV-1 infected
      children.
AB  - Although a number of studies have documented that casual household contact does
      not result in the transmission of HIV, isolated cases of person-to-person
      transmission have been reported. We report a study of household transmission in
      which the families were unaware the children were infected with HIV and thus took
      no precautions to prevent transmission. Twenty-two family members of nine
      transfusion-associated HIV-infected children were studied for transmission of HIV
      in households. There was a total of 174 person-year of household exposure; 76 of
      these exposure years were before the diagnosis of HIV infection in the index
      child. All family members tested negative for HIV by ELISA. Sharing household
      facilities, and interactions with the infected child including kissing, bathing,
      sleeping with, and helping to bathe, dress, and eat, did not result in
      transmission. Interactions that could theoretically result in person-to-person
      transmission occurred in these households such as caring for nose bleeds, biting,
      and home health care procedures. The findings of this and other studies support
      the participation of HIV-infected infants and children in out-of-home care
      programs. It remains prudent, however, to observe current recommendations for
      prevention of HIV-1 for all individuals regardless of whether HIV status is
      known.

PMID- 9545604
TI  - CHARGE association: an update and review for the primary pediatrician.
AB  - CHARGE association is a nonrandom pattern of congenital anomalies that occurs
      together more frequently than one would expect on the basis of chance. This
      common multiple anomaly condition has an estimated prevalence of 1:10,000. The
      number of children diagnosed with CHARGE association is increasing, owing
      presumably to greater awareness of this condition and advances in the care of
      complex, chronically ill children, resulting in improved survival and outcome.
      This review of CHARGE association presents diagnostic criteria that may define a
      concise, recognizable syndrome with a single pathogenetic basis. This review also
      summarizes our current understanding of the management for this complex and
      chronic multiple congenital anomaly condition and discusses the pathogenetic
      basis for this condition.

PMID- 9545606
TI  - Infectious diseases presentations of Munchausen syndrome by proxy: case report
      and review of the literature.
AB  - Munchausen syndrome by proxy is a form of abuse, usually of a child by a parent,
      in which a factitious illness is reported or produced in the child, resulting in
      unnecessary medical evaluations and treatments. A dramatic case of a 17-month-old
      infant with recurrent polymicrobial bacteremia prompted a review of cases
      diagnosed by the Pediatric Infectious Diseases consultation service at our
      referral children's hospital and a review of the infectious diseases
      presentations in the medical literature. The infectious diseases presentations of
      the syndrome as well as criteria for the diagnosis are reviewed and discussed.

PMID- 9545607
TI  - A physician's perspective on dealing with cases of Munchausen by proxy.

PMID- 9545608
TI  - Normal 17-month outcome of a severely hypothermic term neonate.

PMID- 9545609
TI  - Dubowitz syndrome and achalasia: two rare conditions in a child.

PMID- 9545610
TI  - Stool withholding masquerading as seizure disorder.

PMID- 9545611
TI  - Congenital ranula.

PMID- 9545612
TI  - Resident rounds on infant botulism.

PMID- 9545613
TI  - The uncertain diagnosis.

PMID- 9545614
TI  - Iodine intake is a main determinant of thyroid hypersensitivity to acute iodine
      overload.

PMID- 9545615
TI  - The role of quantitative ultrasound in the assessment of bone: a review.
AB  - Quantitative ultrasound (QUS) bone measurement is a promising, relatively new
      technique for the diagnosis of osteoporosis. Unlike to the more established
      method of bone densitometry [measurement of bone mineral density (BMD) e.g. using
      dual X-ray absorptiometry (DEXA)], QUS does not use ionizing radiation. It is
      cheaper, takes up less space and is easier to use than densitometry techniques.
      The two QUS parameters currently measured are broadband ultrasound attenuation
      (BUA) and speed of sound (SOS). The reported age-related changes for healthy
      women range from -0.27% to -1.62% per year for BUA and from -0.06% to -0.19% per
      year for SOS. Precision ranges from 1.0 to 3.8% (CV) for BUA and from 0.19 to
      0.30% (CV) for SOS. The new method of imaging ultrasound has improved the
      precision of QUS measurements. QUS is significantly correlated with BMD. Studies
      with the latest equipment have shown r-values between 0.6 and 0.9 in site
      specific measurements, and QUS is thus believed to reflect mainly BMD. However,
      other studies indicate that QUS measures something other than the actual mineral
      content of bone, namely bone quality, e.g. in vitro studies have shown that QUS
      reflects trabecular orientation independently of BMD. In both cross-sectional and
      prospective studies, QUS seems to be as good a predictor of osteoporotic
      fractures as BMD. In two large prospective studies, QUS also predicted fracture
      risk independently of BMD. QUS has just begun to be used systematically for
      monitoring the response to anti-osteoporotic treatments in prospective trials. In
      the studies performed, QUS has been found to be useful in the follow-up of
      patients. QUS is thus a promising new technique for bone assessment.

PMID- 9545616
TI  - Calf vein compliance increases following bed rest after aortocoronary bypass
      surgery.
AB  - Early post-operative ambulation (< 3 days) is expected to decrease the risk of
      venous thrombosis, whereas late ambulation (> 7 days) increases the risk of
      orthostatic hypotension. The effect of post-operative bed rest on calf vein
      compliance was studied before (D - 1) and 7 days (D + 7) after aortocoronary
      bypass surgery in 50 patients (41 men and nine women, 65 +/- SD 10 years). Calf
      vein compliance was measured by strain gauge plethysmography and stepwise
      increases in thigh congestive pressure from 20 to 60 mmHg. Calf compliance
      [median (25 percentile-75 percentile)] increased significantly by 48% from D - 1
      to D + 7 [0.044 (0.039-0.051) vs. 0.065 (0.048-0.083) ml (100 ml mmHg)-1, P <
      0.001]. This increase was reflected as increased calf volume for the 50 mmHg [D-1
      2.10 (1.75-2.65) vs. D + 7 2.60 (1.70-3.00) ml 100 ml-1, P < 0.01] and 60 mmHg [D
      - 1 2.50 (2.10-2.95) vs. D + 7 3.20 (2.30-4.00) ml 100 ml-1, P < 0.001] occlusion
      pressure levels. The associated pathologies (diabetes and arterial hypertension)
      and NYHA grades had no significant influence on the increase in compliance. Among
      the vasoactive therapeutic regimens, calcium channel blockers contributed
      significantly to the increased calf compliance, but only on D-1. The increase in
      venous compliance following aortocoronary bypass surgery is multifactorial but
      should be considered for prophylactic management of these patients.

PMID- 9545617
TI  - Effect of the H1 blocker d-chlorpheniramine on cerebral blood flow in the
      conscious dog during normocapnic hypoxia.
AB  - The mechanism causing cerebral vasodilatation during hypoxia remains unclear. A
      role for histamine is suspected because H2 receptor-blocking drugs blunt the
      hypoxia-induced increase in cerebral blood flow (CBF). Moreover, in vitro
      blockade of H1 receptors by chlorpheniramine decreases the vasodilatation of
      cerebral arteries that is induced by histamine. The present study tested the
      hypothesis that an H1 receptor blocker (d-chlorpheniramine) would have a similar
      effect in vivo during hypoxia. Isocapnic hypoxia (inspired oxygen fraction, FIO2
      = 0.10; inspired carbon dioxide fraction, FICO2 = 0.035) was induced in 16
      conscious dogs randomly divided into two groups: eight dogs received saline
      intravenously (controls) at time 0 (normoxia) and after 2 h and 4 h hypoxia, and
      the other eight dogs received d-chlorpheniramine intravenously (0.5 mg kg-1) to
      block the H1 receptors. Regional CBF was measured by the radioactive microspheres
      technique 15 min after each injection of d-chlorpheniramine or saline. In the
      control group, CBF increased during hypoxia in all regions of the brain. In the d
      chlorpheniramine group, total CBF increased similarly after 2 h of hypoxia. After
      4 h of hypoxia, the increase was limited, especially in the pons, cerebral
      peduncles, hippocampus, hypothalamus, thalamus, and occipital lobes (six out of
      12 studied regions). It is concluded that the H1 blocker d-chlorpheniramine did
      not strongly inhibit the increase in CBF during hypoxia. After cumulative doses,
      however, as in the fourth hour of hypoxia, the increase in total CBF was limited.

PMID- 9545618
TI  - Lower leg electrical impedance after distal bypass surgery.
AB  - Electrical impedance was determined in 13 patients following distal bypass
      surgery to evaluate lower leg oedema as reflected by its circumference. Tissue
      injury was assessed by the plasma concentration of muscle enzymes. After surgery,
      the volume of the control lower leg increased from 1250 (816-2373) to 1384 (874
      2345) ml (median and range; P < 0.05), where the impedance did not change
      significantly from 140 (92-181) ohms. The volume of the operated leg increased
      more [from 1129 (824-2373) to 1600 (1090-2837) ml], and the decrease in
      electrical impedance was also pronounced [137 (125-169) to 83 (69-104) ohms (P <
      0.001)]. Tissue injury after surgery was indicated by an increase in total
      creatine kinase (n = 17) and MB isoenzyme of creatine kinase (n = 8) (P < 0.05).
      Myoglobin (n = 8) had increased already during surgery (P < 0.05), whereas there
      was no significant change in the plasma concentration of troponin I (n = 8). In
      conclusion, tissue injury was reflected by increases in muscle enzymes in plasma.
      We found an inverse correlation between lower leg electrical impedance and
      volume, but the deviation in electrical impedance was approximately twice that of
      the leg volume. Electrical impedance appears to be a useful method for the
      evaluation of lower leg oedema after distal bypass surgery.

PMID- 9545619
TI  - Effect of head-upright tilt on the dynamic of cerebral autoregulation.
AB  - The effect of head-upright tilting on the rate of cerebral autoregulation was
      studied in 12 healthy volunteers (nine men and three women; age range 20-36
      years). The dynamics of cerebral autoregulation was determined from the rate of
      change in cerebral resistance (RoR) during a drop in arterial blood pressure
      induced by rapid deflation of a 3-min ischaemic thigh cuff and from the ratio of
      changes in cerebral blood flow and arterial blood pressure (CAI) during the
      recovery period after the drop in arterial blood pressure. The test was performed
      supine and with 40 degrees head-up tilt (40 degrees HUT). Middle cerebral artery
      mean blood flow velocity was measured by transcranial Doppler simultaneously with
      peripheral arterial blood pressure using Finapres. The thigh cuff deflation
      induced a larger drop in arterial pressure during 40 degrees HUT [median -28% (25
      percentile -36, 75 percentile -19)] than in the supine position [-16% (-23, -15)]
      (P < 0.01) and in cerebral resistance [supine: -12% (-15, -6); 40 degrees HUT: 
      15% (-20, -12); P < 0.05]. There was no significant change in RoR [15% s-1 (12,
      15)] and CAI [1.9 (1.5, 3.1)] measured supine and during 40 degrees HUT [RoR: 13%
      s-1 (12, 15); CAI: 1.3 (0.99, 1.9)]. During the drop in arterial pressure, the
      relationship between arterial blood pressure and systolic peak-to-peak interval
      exhibited an hysteresis loop, indicating a cardiopulmonary and/or baroreflex
      activation that was not observed with cerebral resistance. The rate of
      autoregulation is an intrinsic property of the cerebral vascular bed and is not
      affected by the vasodilator state in the range of arterial blood pressure changes
      induced by the tight cuff method.

PMID- 9545620
TI  - Diagnostic role of residual volume in paediatric patients with chronic symptoms
      of the lower airways.
AB  - In bronchial asthma, measurement of absolute lung volumes may reveal lung
      dysfunction more readily than forced expiratory spirometry. Sixty-one children
      (aged 4-16 years) with mild to moderate bronchial asthma and 35 children (aged 7
      16 years) with other symptoms of the lower airways (OSLA) were studied, and the
      plethysmographic results were compared with data obtained from 36 healthy
      volunteers aged 6-16 years. In the first test session, repeatability of forced
      expiratory volume in one second (FEV1), forced vital capacity (FVC), residual
      volume (RV), functional residual capacity (FRC) and total lung capacity (TLC)
      were good. Control subjects were also tested the next day, and intra-subject
      variability of repeat pulmonary function testing was in the normal range. The
      FEV1/FVC ratio was significantly higher in control subjects than in patients with
      asthma or OSLA, but only the decrease in RV after bronchodilator challenge
      separated patients with asthma from patients with OSLA. Changes in FEV1 and RV
      after bronchodilator challenge had a significant, although low, inverse
      correlation. An increase of > or = 5% in FEV1 had a positive predictive value of
      44% and a negative predictive value of 68% for the clinical diagnosis of
      bronchial asthma; for a decrease of > or = 24% in RV, the figures were 86% and
      71% respectively. The support of baseline absolute lung volumes on clinical
      decision-making is not necessarily great. Bronchodilator response, particularly
      in RV, is more pertinent and may enhance the detection of reversible lung
      dysfunction.

PMID- 9545621
TI  - Selectivity of superficial vein occlusion at the ankle and calf level: a
      methodological study in healthy volunteers.
AB  - Judgement of deep venous function may be necessary before surgery for superficial
      vein incompetence is performed. Assessment of deep venous function needs
      selective entrapment of superficial venous compartments between the ankle and
      knee, which may not be guaranteed if conventional tourniquets are used. This
      study was, therefore, aimed at modifying the technique of selective compression
      of superficial vein compartments. Twenty apparently normal legs of 10 volunteers
      were investigated on two study days. The subjects were in a supine position with
      the feet resting 30 cm above heart level. Ankle cuffs (3 cm wide) were placed
      just above the malleoli and stepwise inflated with air. The steady-state venous
      volume of the forefoot as a function of the pressure within the ankle cuff was
      measured with a mercury-in-rubber strain gauge. The maximum venous outflow
      velocity from the foot was also measured at each cuff pressure step after the
      addition of conventional thigh vein occlusion. The same protocol was used on the
      second study day: calf cuffs (3 cm wide) were then used instead of the ankle
      cuffs. In the forefoot, venous volume increased and the maximum venous outflow
      velocity decreased significantly either at ankle cuff pressures > 30 mmHg or at
      calf cuff pressures of > 60 mmHg. By using small cuffs, selective superficial
      vein occlusion seems to occur at cuff pressures ranging between 10 and 30 mmHg
      (ankle) and between 30 and 60 mmHg (calf), provided the feet are 30 cm above
      heart level. Higher cuff pressures seem to interact with deep venous function.

PMID- 9545622
TI  - The C-terminal fragment of big endothelin-1 does not potentiate the vasoactive
      effects of endothelin-1.
AB  - The aim was to study the cardiovascular effects of the C-terminal (22-38)
      fragment of big endothelin-1, which is produced by the cleavage of big endothelin
      1 (big ET-1) to endothelin-1 (ET-1). An intravenous infusion of the (22-38)
      fragment (4, 8 and 12 pmol kg-1 min-1, each dose for 10 min) was given to 10
      healthy subjects. Four control subjects received 0.9% saline. Two additional
      subjects received ET-1 1 (0.2 and 4 pmol kg-1 min-1, each dose for 20 min) alone
      or combined with an equimolar infusion of the (22-38) fragment on two separate
      occasions. The fragment infusion did not alter heart rate, mean arterial blood
      pressure, cardiac output, systemic or pulmonary vascular resistance, splanchnic,
      cerebral or forearm blood flow. Renal blood flow showed a slight fall (11%, P <
      0.001) in the fragment group of the same magnitude as in a previous control
      study. After the fragment infusion, a decrease in mean pulmonary arterial
      pressure (MPAP) by 12% (P < 0.01) and in pulmonary capillary wedge pressure
      (PCWP) by 31% (P < 0.001) was noted, which did not differ from the pulmonary
      pressures in the saline-infused control group. The (22-38) fragment, when
      combined with ET-1, was not able to modify the effects of ET-1 on heart rate,
      mean arterial blood pressure, splanchnic and renal blood flow. Consequently, the
      exogenous (22-38) fragment does not seem to cause any significant cardiovascular
      effects in healthy humans.

PMID- 9545623
TI  - Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic
      electrical bioimpedance in obese women.
AB  - Low caloric diet is a commonly accepted treatment in obesity. However, owing to
      moderate results, a pharmacological support has been proposed. As some
      efficacious drugs activate overall sympathetic activity, they might modify
      functions of the cardiovascular system. Three groups of subjects were studied:
      (1) nine obese women receiving only a standard hypocaloric diet; (2) nine obese
      women receiving a standard hypocaloric diet and ephedrine (2 x 25 mg) with
      caffeine (2 x 200 mg); (3) nine obese women receiving a standard hypocaloric diet
      and ephedrine (2 x 25 mg) with caffeine (2 x 200 mg) and yohimbine (2 x 5 mg).
      The cardiovascular state was evaluated by thoracic electrical bioimpedance,
      automatic sphygmomanometry and continuous ECG recording. In each patient, the
      haemodynamic study was performed twice: at rest, i.e. before treatment; and after
      10 days of treatment. On the same days in each patient, the haemodynamic tests
      were performed during physical exercises (handgrip stress and cycloergometer
      exercise). Caffeine and ephedrine had no haemodynamic effect in resting patients.
      These two drugs led to an increase in ejection fraction during cycloergometer
      exercise. Addition of yohimbine increased diastolic pressure and heart rate but
      decreased ejection fraction and stroke index during rest. We also observed that
      addition of yohimbine decreased ejection fraction during the handgrip and
      cycloergometer exercise and increased cardiac load during dynamic exercise.
      Pharmacological supplement of ephedrine and caffeine to a low caloric diet
      modified the cardiovascular system weakly, but the addition of yohimbine to this
      regimen attenuated cardiac performance during rest and handgrip and increased
      cardiac work during dynamic exercise.

PMID- 9545624
TI  - Explaining fertility transitions.
AB  - In this essay, I suggest that the crisis in our understanding of fertility
      transitions is more apparent than real. Although most existing theories of
      fertility transition have been partially or wholly discredited, this reflects a
      tendency to assume that all fertility transitions share one or two causes, to
      ignore mortality decline as a precondition for fertility decline, to assume that
      pretransitional fertility is wholly governed by social constraints rather than by
      individual decision-making, and to test ideas on a decadal time scale. I end the
      essay by suggesting a perceptual, interactive approach to explaining fertility
      transitions that is closely allied to existing theories but focuses on conditions
      that lead couples to switch from postnatal to prenatal controls on family size.

PMID- 9545625
TI  - The rise of divorce and separation in the United States, 1880-1990.
AB  - I use the Integrated Public Use Microdata Series to assess the potential effects
      of local labor-market conditions on long-term trends and race differences in
      marital instability. The rise of female labor-force participation and the
      increase in nonfarm employment are closely associated with the growth of divorce
      and separation. Moreover, higher female labor-force participation among black
      women and lower economic opportunities for black men may account for race
      differences in marital instability before 1940, and for most of such differences
      in subsequent years. However, unmeasured intervening cultural factors are
      probably responsible for at least part of these effects.

PMID- 9545626
TI  - Migration, fertility, and state policy in Hubei Province, China.
AB  - Despite China's one-child family planning policy, the nation experienced a slight
      rise in the birth rate in the mid-1980s. Many observers attributed this rise to
      the heightened fertility of those rural-to-urban migrants who moved without a
      change in registration (temporary migrants), presumably to avoid the surveillance
      of family planning programs at origin and destination. Using a sequential logit
      analysis with life-history data from a 1988 survey of Hubei Province, we test
      this possibility by comparing nonmigrants, permanent migrants, and temporary
      migrants. While changing family planning policies have a strong impact on timing
      of first birth and on the likelihood of higher-order births, migrants generally
      do not have more children than nonmigrants. In fact, migration tends to lower the
      propensity to have a child. More specifically, the fertility of temporary
      migrants does not differ significantly from that of other women.

PMID- 9545627
TI  - Sibling models of socioeconomic effects on the timing of first premarital birth.
AB  - Data on 1,000 pairs of sisters from the National Longitudinal Survey of Youth are
      used to estimate the effects of observed individual-level factors, common family
      level variables, and shared unobserved family-level traits on the timing of
      premarital births. Results show a moderate correlated risk of premarital
      childbearing among siblings after controlling for the effects of measured
      covariates. The effect of older sisters' out-of-wedlock childbearing on the
      timing of younger sisters' premarital birth is overestimated when shared
      unmeasured family-level traits are ignored. Public policy measures designed to
      reduce premarital births have a smaller multiplier effect via reduced younger
      sisters' premarital births because unmeasured family-level factors are less
      amenable to policy measures. However, because the older-sibling effect is large
      when other sources of variability in premarital birth timing are controlled,
      interventions may be effective in reducing premarital births among young women in
      high-risk families.

PMID- 9545628
TI  - Effect of provider characteristics on choice of contraceptive provider: a two
      equation full-information maximum-likelihood estimation.
AB  - We use surveys of households and health-care facilities conducted in the same
      area at the same time to determine which characteristics of providers attract
      users of contraceptives. By using the full-information maximum-likelihood
      technique to jointly estimate choice of contraceptive method and choice of
      provider, we avoid self-selection bias. Results support the need for modeling
      quality and for jointly estimating the choice of contraceptive method and the
      choice of provider to avoid biased estimates of coefficients. The results suggest
      that for the Cebu, Philippines region, small local clinics that focus on family
      planning tend to be most favored by clients.

PMID- 9545629
TI  - Residential mobility between cities and suburbs: race, suburbanization, and back
      to-the-city moves.
AB  - Information from the 1979 to 1986 waves of the Panel Study of Income Dynamics is
      merged with data on respondents' tract and metropolitan area of residence to
      examine patterns and determinants of residential mobility between central cities
      and suburbs. Consistent with the life-cycle model of residential mobility,
      mobility in both directions declines with age, but on balance the presence of
      young children deters moving to the suburbs. Among blacks, education increases
      the probability of moving from cities to suburbs, while high income retains
      blacks and whites in suburbs. Consistent with the place stratification model,
      blacks are substantially less likely than whites to move from cities to suburbs,
      and substantially more likely to move from suburbs to cities, even after
      standardizing for racial differences in sociodemographic characteristics. High
      levels of violent crime and unemployment in cities relative to suburbs also tend
      to spur city-to-suburb mobility or inhibit suburb-to-city moves.

PMID- 9545630
TI  - An occupational tale of two cities: minorities in London and New York.
AB  - In this paper, queuing theory is tested through an examination of the
      occupational attainment of six groups of non-whites in London and New York.
      Workers in the dominant economy are distinguished from those in the niche economy
      and emphasis is placed on the former. Black male immigrants in New York and black
      female immigrants in London hold more favorable occupational status. These
      results reflect differences in (1) the presence of indigenous minorities--African
      Americans and Puerto Ricans--in New York but not London, and (2) the relatively
      low position of indigenous minority males compared to the relatively middling
      position of indigenous minority females in New York's labor queue.

PMID- 9545631
TI  - Age-distribution dynamics and aging indexes.
AB  - I analyze the dynamics of the age distribution as some vital rates change. When
      the fertility or mortality rate declines, the age distribution often manifests a
      dynamic stochastic-dominance relationship. I also propose some alternative
      indexes for measuring population aging. These indexes are closely connected with
      the age-distribution dynamics and contain more refined information about the
      distribution of age among the old.

PMID- 9545632
TI  - Structure and methylation-based silencing of a gene (DBCCR1) within a candidate
      bladder cancer tumor suppressor region at 9q32-q33.
AB  - Loss of heterozygosity (LOH) on chromosome 9q is the most frequent genetic
      alteration in transitional cell carcinoma (TCC) of the bladder, indicating the
      presence of one or more relevant tumor suppressor genes. We previously mapped one
      of these putative tumor suppressor loci to 9q32-q33 and localized the candidate
      region within a single YAC 840 kb in size. This locus has been designated DBC1
      (for deleted in bladder cancer gene 1). We have identified a novel gene, DBCCR1,
      in this candidate region by searching for expressed sequence tags (ESTs) that map
      to YACs spanning the region. Database searching using the entire DBCCR1 cDNA
      sequence identified several human ESTs and a few homologous mouse. ESTs. However,
      the predicted 761-amino-acid sequence had no significant homology to known
      protein sequences. Mutation analysis of the coding region and Southern blot
      analysis detected neither somatic mutations nor gross genetic alterations in
      primary TCCs. Although DBCCR1 was expressed in multiple normal human tissues
      including urothelium, mRNA expression was absent in 5 of 10 (50%) bladder cancer
      cell lines. Methylation analysis of the CpG island at the 5' region of the gene
      and the induction of de novo expression by a demethylating agent indicated that
      this island might be a frequent target for hypermethylation and that
      hypermethylation-based silencing of the gene occurs in TCC. These findings make
      DBCCR1 a good candidate for DBC1.

PMID- 9545634
TI  - Cloning and localization of the murine Xpct gene: evidence for complex
      rearrangements during the evolution of the region around the Xist gene.
AB  - The overall organization of the X-inactivation center (XIC/Xic) candidate region
      seems poorly conserved between human and mouse. The orientation of a region
      containing the X-inactive-specific transcript (Xist/ XIST) gene and three genes
      located 3' of Xist/XIST has been shown to be inverted between the two species,
      although the actual extent of this rearrangement is unknown. We have cloned and
      mapped the mouse homolog of the human XPCT (X-linked PEST-containing transporter)
      gene, which encodes a putative transmembrane transporter. Human XPCT is located
      about 200 kb outside of the XIC candidate region and 600 kb 5' of or telomeric to
      the XIST gene. The mouse Xpct gene, which lies approximately 300 kb 5' of and
      centromeric to Xist, displays 85% identity at the nucleotide level with the human
      gene, and the overall protein structure is conserved. The transcriptional
      orientation of mouse Xpct with respect to Xist is the opposite of that in human.
      Consequently, the evolution of the region between human and mouse appears to be
      highly complex, with structural rearrangements involving a region of up to 600 kb
      or more around the Xist gene.

PMID- 9545633
TI  - Partial deletion of both the spermine synthase gene and the Pex gene in the X
      linked hypophosphatemic, gyro (Gy) mouse.
AB  - Gy, along with Hyp, is a dominant mutation of the normal gene Pex causing X
      linked hypophosphatemia in the mouse. Hemizygous Gy male mice, however, have
      greater defects in survival, bodily growth, skeletal mineralization, and
      neurological function than those found in heterozygous Gy females or in Hyp mice.
      Since the gene for spermine synthase is immediately upstream of the homologous
      human gene PEX, we compared the effects of the Gy and Hyp mutations on both the
      spermine synthase gene and the Pex gene. Barely detectable levels of spermine (<
      5% of normal) with elevated levels of its precursor, spermidine, were found in
      organs of Gy male mice compared to normal male littermates. Neither Gy females
      nor Hyp male mice were significantly affected. Four missing introns of the
      spermine synthase gene were identified in Gy male mice, suggesting extensive gene
      disruption. A pseudogene for spermine synthase was also identified in the mouse
      genome. Pex mRNA was found in several but not all tissues studied in adult normal
      mice. Pex mRNA was altered in both Gy and Hyp mice. All male Hyp mice were
      lacking the 3' end of the Pex message, whereas all male Gy mice were deficient at
      the 5' end. In summary, the Gy mutation is associated with a recessively
      expressed mutation of the spermine synthase gene, leading to spermine deficiency,
      and a dominantly expressed mutation of the Pex gene, leading to hypophosphatemia.
      Alterations in two contiguous genes in Gy may explain the additional phenotypic
      abnormalities present in the Gy male mouse.

PMID- 9545636
TI  - Genomic DNA sequence, promoter expression, and chromosomal mapping of rat muscle
      carnitine palmitoyltransferase I.
AB  - Carnitine palmitoyltransferase I (CPT-I) is a key enzyme involved in the
      regulation of fatty acid oxidation. CPT-IA and CPT-IB are isoforms of carnitine
      palmitoyltransferase I, of which CPT-IA is expressed in liver, kidney,
      fibroblasts, and heart and CPT-IB is expressed in skeletal muscle, heart, brown
      and white adipocytes, and testes. Although the genomic DNA sequence of human CPT
      IB is available, the transcription start site and upstream regulatory sequences
      are not known. For rat CPT-IB, only the cDNA sequence has been published. We have
      cloned the entire rat CPT-IB gene from a Lambda fix II rat kidney genomic
      library. The genomic structure contains 19 exons, with the transcription start
      site for CPT-IB located in a short first exon, which is a 13-bp extension to the
      previously published cDNA 5' sequence. The coding sequence is identical with the
      rat muscle cDNA. The rat CPT-IB gene contains 18 introns and 19 exons, the latter
      18 exons showing 85% homology to the human CPT-IB cDNA. CPT-IB maps to rat
      chromosome 7 at band q34. A putative promoter region was identified to within 391
      bp of the transcription start site. The muscle specificity of the 5' flanking
      region was verified by comparison of luciferase expression to that of beta
      galactosidase in cardiac myocytes and in HepG2 cells.

PMID- 9545635
TI  - The mouse Y chromosome: enrichment, sizing, and cloning by bivariate flow
      cytometry.
AB  - In this report, we demonstrate the utility of interleukin-2 (IL-2) stimulation of
      spleen cell cultures and bivariate flow cytometry in the analysis and
      purification of the C57BL/6J mouse Y Chromosome. We determined that the DNA
      content of the C57BL/6J Y Chromosome is approximately 94.7 Mb, making it similar
      in size to human Chromosome 16 and significantly larger than previous estimates.
      In addition, we describe the bulk isolation of mouse Y Chromosomes and
      demonstrate enrichment of the isolated material using a fluorescence in situ
      hybridization strategy. We detail the construction of two small insert Y
      Chromosome-specific libraries, ideal for sampling Y Chromosome sequences. From
      these libraries 1566 clones were analyzed. We provide a detailed characterization
      of 103 clones, generating nearly 50 kb of sequence. For 30 of these clones, we
      identify regions of homology to known Y chromosomal sequences, confirming the
      enrichment of the sorted DNA. From the remaining characterized clones, we
      describe the development of 15 male-specific PCR assays and 19 male-female PCR
      assays potentially originating from the pseudoautosomal region or other areas of
      X-Y or autosome-Y homology.

PMID- 9545639
TI  - Homozygosity mapping of autosomal recessive retinitis pigmentosa locus (RP22) on
      chromosome 16p12.1-p12.3.
AB  - Autosomal recessive retinitis pigmentosa (arRP) is a genetically and clinically
      heterogeneous and progressive degenerative disorder of the retina, leading
      usually to severe visual handicap in adulthood. To date, disease loci/genes have
      been mapped/identified only in a minority of cases. DNA samples were collected
      from 20 large consanguineous Indian families, in which arRP segregated and that
      were suitable for homozygosity mapping of the disease locus. After excluding
      linkage to all known arRP loci, a genome-wide scan was initiated. In two
      families, homozygosity mapping, haplotype analysis, and linkage data mapped the
      disease locus (RP22) in an approximately 16-cM region between D16S287 and D16S420
      on the proximal short arm of chromosome 16. No mutation has been found by direct
      sequencing in the gene (CRYM) encoding micron crystallin, which maps in the
      critical region.

PMID- 9545638
TI  - Identification and characterization of two putative human arginine
      methyltransferases (HRMT1L1 and HRMT1L2).
AB  - RNA-binding proteins such as heterogeneous nuclear ribonucleoproteins (hnRNPs),
      which contain the bulk of methylated arginine residues in eukaryotic cells, play
      many essential roles in the metabolism of nuclear pre-mRNA. Arginine
      methyltransferase activity has also been implicated in signal transduction events
      with components of the cellular growth and viral response pathways. We recently
      characterized a single yeast hnRNP methyltransferase (HMT1). We now present the
      identification and characterization of two putative human arginine
      methyltransferases termed HRMT1L1 and HRMT1L2. In addition to methyltransferase
      similarities, the N-terminal region of the HRMT1L1 protein contains an Src
      homology 2 domain. HRMT1L1 maps to a YAC containing the telomere of chromosome
      21q. Three alternatively spliced HRMT1L2 transcripts with variable 5'-ends were
      observed, encoding proteins of 343, 347, and 361 amino acids, respectively.
      HRMT1L2 maps to human chromosome 19q. Recombinant HRMT1L2 protein encoded by the
      most common 5'-variant exhibited methyltransferase activity in vitro.
      Furthermore, in vivo activity was demonstrated by complementation of a yeast HMT1
      mutant strain. The identification of highly conserved Hmt1p human homologues that
      function in yeast indicates that analyses of this class of enzymes in yeast may
      be directly applicable to higher eukaryotes. The possible roles of HRMT1L1 and
      HRMT1L2 in human disease are currently unknown.

PMID- 9545637
TI  - Molecular cloning, structural characterization, and chromosomal mapping of the
      human LECT2 gene.
AB  - We originally isolated LECT2 (leukocyte cell-derived chemotaxin 2) as a 16-kDa
      secreted protein having a human neutrophil chemotactic activity, then cloned
      human and bovine LECT2 cDNAs and demonstrated the liver-specific expression of
      the protein. LECT2 is thought to be a multifunctional protein, because it was
      recently found to be identical to chondromodulin-II a growth stimulator of
      chondrocyte cells. We report here the cloning and the structural analysis of the
      human LECT2 gene. The gene spans approximately 8 kb and consists of four exons
      and three introns. Primer extension analysis revealed that several transcription
      initiation sites occur within 70-230 nucleotides upstream of the translation
      initiation codon. Several transcriptional control sequences relevant to the liver
      specific expression have been identified at the 5' untranslated region of the
      human LECT2 gene. The human LECT2 gene was mapped to chromosome 5q31.1-q32 by
      fluorescence in situ hybridization. This region contains a cluster of cytokine
      genes including IL-4, IL-5, and IL-9.

PMID- 9545640
TI  - A high-resolution genetic map of the nervous locus on mouse chromosome 8.
AB  - The nervous (nr) mutant mouse displays two gross recessive traits: both an
      exaggeration of juvenile hyperactivity and a pronounced ataxia become apparent
      during the third and fourth postnatal weeks. Using an intersubspecific
      intercross, we have established a high-resolution map of a segment of mouse
      chromosome 8 that places the nr locus in a genomic segment defined by D8Rck1 on
      the centromeric end and D8Mit3 on the telomeric end. This map position places the
      nr locus within the BALB/cGr congenic region of the C3HeB/ FeJ-nr strain,
      confirming the accuracy of our study. We used this map position to identify and
      evaluate three genes-ankyrin 1, cortexin, and farnesyltransferase-as candidates
      for the nr gene. These three genes were eliminated from consideration but allowed
      us to establish the conservation of synteny between the region containing the nr
      locus and a segment of the short arm of human chromosome 8 (8p21-p11.2). Finally,
      the incomplete penetrance of the nr phenotype led us to perform a screen for
      modifier loci, and we present evidence that such a nervous modifier locus may
      exist on mouse chromosome 5.

PMID- 9545642
TI  - Physical linkage of the B29/Ig-beta (CD79B) gene to the skeletal muscle, sodium
      channel, and growth hormone genes in rat and human.
AB  - In the region between the polyadenylation site of the rat skeletal muscle (SkM)
      Na-channel gene and the 5' end of the growth hormone (GH) gene, a gene coding for
      B-cell-specific membrane protein B29/Ig-beta was found and noted to have the same
      orientation as the Na-channel and GH genes. Rat B29/Ig-beta gene was 3.1 kb in
      length with six exons and was separated by 3.3 and 9.3 kb from Na-channel and GH
      genes, respectively. Rat B29/Ig-beta protein comprised 228 amino acids, and its
      amino acid sequence was 85 and 69% identical with the mouse and human
      counterparts, respectively. With the long-area PCR method, genomic DNA connecting
      human SkM Na-channel (SCN4A) and B29/Ig-beta (CD79B) genes and CD79B and GH (GH1)
      genes was amplified, and the physical linkage of SCN4A/CD79B/ GH1 genes in the
      human genome was established. The human CD79B gene was separated by 6.3 and 10.5
      kb from the SCN4A and GH1 genes, respectively.

PMID- 9545641
TI  - Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate
      gene for Hirschsprung disease susceptibility.
AB  - Congenital aganglionic megacolon, commonly known as Hirschsprung disease (HSCR),
      is the most frequent cause of congenital bowel obstruction. Germline mutations in
      the RET receptor tyrosine kinase have been shown to cause HSCR. Knockout mice for
      RET and for its ligand, glial cell line-derived neurotrophic factor (GDNF),
      exhibit both complete intestinal aganglionosis and renal defects. Recently, GDNF
      and GFRA1 (GDNF family receptor, also known as GDNFR-alpha), its GPI-linked
      coreceptor, were demonstrated to be components of a functional ligand for RET.
      Moreover, GDNF has been implicated in rare cases of HSCR. We have mapped GFRA1 to
      human chromosome 10q25, isolated human and mouse genomic clones, determined the
      gene's intron-exon boundaries, isolated a highly polymorphic microsatellite
      marker adjacent to exon 7, and scanned for GFRA1 mutations in a large panel of
      HSCR patients. No evidence of linkage was detected in HSCR kindreds, and no
      sequence variants were found to be in significant excess in patients. These data
      suggest that GFRA1'S role in enteric neurogenesis in humans remains to be
      elucidated and that RET signaling in the gut may take place via alternate
      pathways, such as the recently described GDNF-related molecule neurturin and its
      GFRA1-like coreceptor, GFRA2.

PMID- 9545643
TI  - Construction of a 1.5-Mb bacterial artificial chromosome contig in Xp11.23, a
      region of high gene content.
AB  - To generate sequence-ready templates for the gene-rich Xp11.23 region, we have
      constructed a 1.5-Mb bacterial artificial chromosome (BAC) contig spanning the
      interval between the DNA markers OATL1 and DXS255. The contig includes 28 BACs,
      ranging in size from 58 to 258 kb with an average size of 135 kb, which provide
      2.5-fold coverage of the region. The BAC contig was constructed based entirely on
      the content of 40 DNA markers from a previously established YAC contig and 11 new
      markers developed from BAC-end DNA sequences, 4 of which were required to close
      gaps in the map. There was no evidence of rearrangement, instability, or
      chimerism in any of the BAC clones. The BAC cloning system appears to provide
      robust and total physical coverage of this gene-rich region with clones that are
      suitable for DNA sequencing.

PMID- 9545644
TI  - Identification and characterization of the human ortholog of rat STXBP1, a
      protein implicated in vesicle trafficking and neurotransmitter release.
AB  - In a screen designed to identify genes expressed preferentially in retina, we
      identified a cDNA encoding the human ortholog of rat STXBP1 (n-Sec1, Munc-18-1,
      rbSec1), a protein implicated in vesicle trafficking and neurotransmitter
      release. This protein also has similarity to Drosophila Rop (65% aa identity) and
      Caenorhabditis elegans UNC-18 (58% aa identity). The major human cDNA encodes a
      protein of 594 amino acids which has 100 % amino acid identity with its rat and
      murine counterparts. Additionally, there is an alternative splice form in humans,
      arising from the inclusion of an additional exon, which encodes a protein of 603
      amino acids and is also 100% identical to the corresponding rat isoform. We found
      expression of the shorter cDNA in all tissues and cell lines we examined with
      highest levels in retina and cerebellum. By RT-PCR analysis, we found expression
      of the longer cDNA in neural tissues only. We mapped the structural gene to
      9q34.1, a region without obvious candidate phenotypes. However, due to its
      evolutionary conservation and abundant expression in retina and brain, STXBP1
      should be considered a candidate gene for retinal and/or neural disorders mapping
      to 9q34.1.

PMID- 9545645
TI  - Genomic organization of the human SPOCK gene and its chromosomal localization to
      5q31.
AB  - SPOCK, previously identified as testican, is a modular proteoglycan that carries
      both chondroitin and heparan sulfate glycosaminoglycan side chains. The overall
      genomic organization has been established. The SPOCK gene spans at least 70 kb
      and is composed of 11 exons: the first half of the gene is dramatically expanded,
      but the second half is more compact. In situ hybridization and YAC mapping
      independently linked the SPOCK gene to 5q31, a region containing an impressive
      number of genes encoding growth factors, cytokines, and neurotransmitter and
      hormone receptors. The gene is located between the IL9 and the EGR1 genes,
      bordering the smallest commonly deleted region of chromosome 5.

PMID- 9545646
TI  - The identification and localization of a human gene with sequence similarity to
      Polycomblike of Drosophila melanogaster.
AB  - The Drosophila Polycomb group (PcG) of genes is required for the epigenetic
      regulation of a number of important developmental genes, including the homeotic
      (Hox) genes. The members of this gene family encode proteins that do not share
      sequence similarity, implying that each plays a unique role in this epigenetic
      repression mechanism. Polycomblike (Pcl) was the second PcG gene to be
      identified. We report here the isolation and characterization of a human cDNA,
      termed PHF1, which encodes a protein with significant sequence similarity to
      Drosophila Polycomblike (PCL). The region of similarity between PHF1 and PCL
      includes the two PHD fingers (C4-H-C3 motif), the region between them, and
      sequences C-terminal to the PHD fingers. PHF1 and PCL are 34% identical over this
      258-residue region. PHF1 was mapped to 6p21.3 by fluorescence in situ
      hybridization. While several genetic diseases that are likely to result from
      developmental abnormalities map to this region, PHF1 is not a clear candidate
      gene for any of them.

PMID- 9545648
TI  - Endothelial Tie2/Tek ligands angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2):
      regional localization of the human genes to 8q22.3-q23 and 8p23.

PMID- 9545647
TI  - Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1)
      specifying putative components of the mitochondrial gene expression apparatus.
AB  - We have mapped the chromosomal locations of three human nuclear genes for
      putative components of the apparatus of mitochondrial gene expression, using a
      combination of in situ hybridization and interspecies hybrid mapping. The genes
      RPMS12 (mitoribosomal protein S12, a conserved protein component of the
      mitoribosomal accuracy center), TUFM (mitochondrial elongation factor EF-Tu), and
      AFG3L1 (similar to the yeast genes Afg3 and Rca1 involved in the turnover of
      mistranslated or misfolded mtDNA-encoded polypeptides) were initially
      characterized by a combination of database sequence analysis, PCR, cloning, and
      DNA sequencing. RPMS12 maps to chromosome 19q13.1, close to the previously mapped
      gene for autosomal dominant hearing loss DFNA4. The TUFM gene is located on
      chromosome 16p11.2, with a putative pseudogene or variant (TUFML) located very
      close to the centromere of chromosome 17. AFG3L1 is located on chromosome 16q24,
      very close to the telomere. By virtue of their inferred functions in
      mitochondria, these genes should be regarded as candidates of disorders sharing
      features with mitochondrial disease syndromes, such as sensorineural deafness,
      diabetes, and retinopathy.

PMID- 9545649
TI  - Individual differences and cardiovascular responsivity.

PMID- 9545650
TI  - Psychosocial influences on blood pressure during daily life.
AB  - Ambulatory blood pressure (ABP) monitoring allows frequent non-invasive blood
      pressure (BP) recordings in a variety of settings. Emerging evidence suggests
      that ABP is a better predictor of cardiovascular morbidity than clinic BP.
      Ambulatory blood pressure is influenced by a variety of physical, psychological
      and behavioral factors that comprise an individual's daily life. The present
      article reviews psychosocial research relating ABP to psychological factors (e.g.
      Type A behavior pattern, anger/hostility) and environmental influences (e.g. job
      strain). Psychological factors and environmental factors alone and in interaction
      with each other appear to substantially influence ABP. Interacting physical,
      psychosocial and behavioral factors that comprise daily life provide unique
      methodological challenges to ABP research. Methodological considerations (e.g.
      activity patterns, caffeine and alcohol consumption) for performing ABP research
      are discussed. Evidence outlined in this review suggests that psychosocial
      factors contribute to ABP level. To the extent that psychosocial factors
      contribute to ABP cardiac disease, it will be important to analyze their effects
      on underlying disease processes.

PMID- 9545651
TI  - Sociotropic cognition moderates blood pressure response to interpersonal stress
      in high-risk adolescent girls.
AB  - This article tests the hypothesis that 'sociotropic cognition'--heightened
      preoccupation with being accepted by others--increase vulnerability to
      cardiovascular stress in females. Adolescent girls (55 African-American; 23
      Caucasian) at increased risk of developing essential hypertension due to
      persisting high normal blood pressure, completed measures of sociotropic
      cognition, social competence, trait affect and social support. Later, their blood
      pressure and heart rate were measured during non-social stress (mirror image
      tracing) and interpersonal stress [Social Competence Interview (SCI)].
      Comparisons of blood pressure responses to the tasks disclosed a significant Task
      main effect, replicating a previous finding that blood pressure is elevated more
      by SCI than by non-social stress. When Sociotropy was introduced as a moderator,
      however, a significant Task by Sociotropy interaction indicated that the
      comparatively greater reactivity to SCI occurred mainly in girls who exhibited
      high levels of sociotropic thinking. Cognitive sociotropy was associated with a
      profile of social emotional and environmental deficits suggesting increased
      susceptibility to chronic stress and impaired coping.

PMID- 9545652
TI  - Stress and personality as factors in women's cardiovascular reactivity.
AB  - An experiment was conducted to investigate the relationships among Type A
      behavior, hostility and cardiovascular reactivity (CVR) in women. Changes in
      heart rate, blood pressure and skin conductance from baseline to task levels were
      used to assess reactivity. These measures were obtained from 96 women during a
      seated baseline period, a reaction time task and during an oral IQ quiz. Analyses
      indicated that Type A and high hostile women were more reactive to an oral IQ
      quiz and reaction time stressors than Type B and low hostile women. Specifically,
      Type As showed significantly greater increases in systolic blood pressure in the
      reaction time task and greater mean arterial pressure and systolic blood pressure
      increases in the IQ quiz. High hostiles evidenced significantly higher systolic
      blood pressure and diastolic blood pressure in the RT task and higher mean
      arterial pressure and diastolic blood pressure in the IQ quiz. It was concluded
      that Type A personality and hostility can predict greater reactivity in women to
      two different stressors. The oral quiz generated greater reactivity than the RT
      task and thus may be a more stressful task.

PMID- 9545653
TI  - Enhanced cardiovascular and catecholamine responses in women with depressive
      symptoms.
AB  - To test the hypothesis that cardiovascular and sympathetic nervous system
      responses before and during behavioral stressors are exaggerated among subjects
      with depressed mood who do not have clinical depressive disorder. Sixty healthy
      women aged 18-49 were initially asked to complete the Beck Depression Inventory
      (BDI). The 15 with the highest (Depressive Symptom group) and the 15 with the
      lowest BDI scores (Control group) underwent stress testing including baseline,
      postural challenge, a speech task describing responses to a recent anger-arousing
      experience and recovery. Both systolic and diastolic blood pressure levels were
      higher in the Depressive Symptom group during baseline, challenges and recovery.
      This group also showed shorter pre-ejection period (a marker of enhanced cardiac
      sympathetic activation) and lesser heart rate variability across all test
      periods. During the speech task only, the Depressive Symptom group exhibited
      greater increases in plasma norepinephrine and higher cardiac output responses
      associated with decreased interbeat interval (faster heart rate). These results
      support the a priori hypothesis regarding enhanced sympathetic and cardiovascular
      activity. Finally, the BDI scores correlated very highly with lack of perceived
      emotional social support, reinforcing prior research on the linkage between
      social isolation and severity of depressive symptoms.

PMID- 9545654
TI  - Serum lipid concentrations, hostility and cardiovascular reactions to mental
      stress.
AB  - The objective of the present study was to determine whether serum lipid
      concentrations interact with hostility to affect cardiovascular responses to
      mental stress. One-hundred and seventy-four male subjects were screened with the
      Cook and Medley hostility scale (Ho), the anger expression inventory by
      Spielberger and a general health questionnaire. Subjects in the upper (n = 22)
      and lower (n = 22) quartile of the Ho score distribution were asked to take part
      in a laboratory experiment. Continuous measures of heart rate, blood pressure,
      respiration and electrodermal activity were taken while participants carried out
      a series of behavioral maneuvres, including mental arithmetic and mirror star
      tracing. Prior to the experiment fasting blood samples were taken for lipid
      determinations. The results show higher heart rate reactivity in high hostile
      than low hostile subjects. High hostile subjects also reported more anger and
      frustration in response to tasks. Hostility groups differed in lipid levels in
      that high hostiles had higher triglyceride and VLDL-c concentrations than low
      hostiles. Cholesterol levels showed an inverse association with cardiovascular
      reactivity but only in low hostile subjects. No such associations could be found
      in high hostiles. We conclude that there is partial support for both, the
      hyperreactivity and the health behavior model linking hostility and
      cardiovascular disorder.

PMID- 9545656
TI  - Parental history of hypertension and hostility moderate cardiovascular responses
      to interpersonal conflict.
AB  - A parental history of hypertension has been implicated in the development of
      hypertension, perhaps by virtue of an elevated cardiovascular response to stress.
      Similarly, hostility has been hypothesized to be linked to cardiovascular disease
      through cardiovascular hyperreactivity. The interaction of parental history and
      hostility in moderating cardiovascular response has been infrequently examined,
      though research suggests the two may be linked through familial factors. The
      present study examined the cardiovascular response of 98 healthy young adult
      males categorized as offspring of hypertensive subjects (PH+) or offspring of
      normotensive subjects (PH-) and as high or low hostile, based on Cook-Medley
      Hostility scores (HiHo vs. LoHo). Subjects were exposed to either an harassment
      or non-harassment stressor. Results indicated elevated cardiac output and forearm
      blood flow responses in PH+/HiHo subjects who were harassed as compared to any
      other harassed subject and all non-harassed individuals. This hemodynamic
      response pattern of elevated blood flow suggests a mechanism of hypertensive
      disease development.

PMID- 9545655
TI  - Interactive effects of trait hostility and anger expression on cardiovascular
      reactivity in young men.
AB  - Hostility and anger-expression style are personality traits often associated with
      elevated cardiovascular reactivity and potential heightened risk for
      cardiovascular disease. In the present study a sample of 50 young, healthy men
      were divided into groups low or high on the Cook-Medley Hostility scale and on
      anger-out from Spielberger's Anger Expression scale. Subjects worked on mental
      arithmetic and public speaking tasks in counterbalanced order. Heart rate,
      systolic and diastolic blood pressure and hemodynamic indices were measured at
      baseline and during the tasks. Hostility and anger-out interacted in their
      effects on cardiovascular responses. The High Anger-Out/Low-Hostile group
      displayed the greatest increases in heart rate and blood pressures, while the
      High Anger-Out/High-Hostile group was least reactive. Furthermore, the High Anger
      Out/Low-Hostile group showed a distinct fight/flight response pattern during
      public speaking, indicated by increases in stroke volume and cardiac output and a
      decrease in systemic vascular resistance. These results suggest that a mismatch
      between hostile cognitions and habitual anger expression leads to greater
      cardiovascular reactivity to challenging tasks, potentially enhancing risk for
      development of cardiovascular diseases.

PMID- 9545657
TI  - Family history of hypertension: a psychophysiological analysis.
AB  - Family history of hypertension (positive and negative) and gender groups were
      compared on cardiovascular responses at rest, during stressors and during
      recovery. Two tasks were employed, mental arithmetic and an anger recall
      interview. Both levels and reactivity measures of blood pressure, heart rate,
      cardiac output and total peripheral resistance were included. In addition,
      participants filled out several questionnaires measuring state feelings during
      the task and recovery periods, trait anger/hostility and emotions. Both men and
      women with a positive family history of hypertension exhibited higher tonic
      levels of blood pressure and heart rate at rest, recovery and during both tasks.
      They also exhibited greater heart rate reactivity during the mental arithmetic
      task and greater blood pressure reactivity to both tasks when post-math recovery,
      but not initial rest, was used as a covariate. Positive family history
      individuals reported less trust and gregariousness, more depression and
      aggression, less awareness of somatic responses to the tasks and less effort to
      relax during the post-task rest periods. Finally, significant correlations were
      found between low anger expression how anger experience and high anger control
      and task SBP levels in positive family history individuals.

PMID- 9545658
TI  - Effects of threat of shock, shock electrode placement and darkness on startle.
AB  - Fear can be elicited by physically-presented explicit threat stimuli or by more
      static contextual stimuli that are not an immediate source of danger. Research in
      both humans and animals suggest that fear produced by these two types of stimuli
      represents separate processes mediated by different brain structures. The present
      study used the startle reflex methodology to examine affective responses elicited
      by an explicit threat cue signalling a period of shock anticipation and by two
      types of contextual stimuli; darkness and attaching the shock electrodes. As
      expected, shock anticipation potentiated startle (fear-potentiated startle).
      Startle was also facilitated by darkness and by the placement of shock
      electrodes. Further, darkness increased fear-potentiated startle to an explicit
      threat cue, but did not affect the facilitation of startle produced by attaching
      the shock electrodes. It is suggested that affective responses to contextual
      stimuli should be considered when investigating both normal and pathological
      fear.

PMID- 9545660
TI  - Responses to irrelevant probes during task-induced negative and positive shifts.
AB  - The functional significance of task-induced negative and positive cortical shifts
      were tested with the probe-stimulus method. Both shifts were induced within the
      same experimental situation in three variants of a CNV paradigm, where a slow
      positive wave (a variant of P300) appeared following S2. In Experiment I and II,
      S2 called for making or withholding a motor response (go/no-go); in Experiment
      III, S2 informed the subject about the correctness of a previous guess.
      Irrelevant probe-stimuli were applied in conjunction with the task during the
      CNV, the post-S2 positivity and the intertrial interval (ITI). The probe-evoked
      vertex EPs were smaller during the post-S2 positivity as compared to the CNV and
      the ITI. This was true not only for the motor task but also for the guessing
      task, where the effect is unlikely to have been contaminated by motor potentials.
      This indicates that positive shifts have an inhibitory effect on the processing
      of irrelevant probe-stimuli and possibly on information-processing in general.

PMID- 9545659
TI  - P300 correlates of simulated malingered amnesia in a matching-to-sample task:
      topographic analyses of deception versus truthtelling responses.
AB  - Two experiments using a P300-enhanced Forced Choice Procedure (P3FCP)
      investigated simulated amnesia in a matching-to-sample task. In Experiment 1,
      successful manipulation of subjects towards different behavioral hit rates (75
      80% vs. 85-90%) did not adversely affect the diagnostic sensitivity of match
      mismatch Pz-P300 amplitude analyses, allowing detection of 69% of simulators.
      P300 amplitudes of simulators (Malinger group) were as large as those of truth
      tellers (truth group, a control), indicating no dual task-related (Malingering)
      reduction across different behavioral hit rates. Experiment 2 found no main
      effect of oddball type, match vs. mismatch, on P300 (P3) amplitude with a
      mismatch-rare variant of the P3FCP. This study also revealed larger Pz-P3s in the
      Malingering (vs. Truth-telling) condition. Subsequent topographic analyses
      suggested different Truth and Malinger scaled P3 amplitude topographies in both
      these sets of P3FCP data and in those from a previous autobiographical memory
      paradigm. Further analysis yielded preliminary evidence for a common deception
      related P3 amplitude topography across different paradigms/conditions.

PMID- 9545661
TI  - Psychophysiological effects of interviews about emotional events on offspring of
      hypertensives and normotensives.
AB  - Normotensive individuals with a parental history of hypertension have been found
      to exhibit greater cardiovascular reactivity to a variety of laboratory stressors
      than offspring of normotensives. To examine the possible generalization of these
      differences to real-life stressors, subjects were administered four brief
      interviews about different emotional events in their lives. Regardless of
      emotional content, offspring of hypertensives displayed greater systolic blood
      pressure responses to the non-verbal recollection and verbal description of
      personal emotional events, but not to the imagination of standardized emotional
      scenes or reading a non-emotional advertisement. This suggests that group
      differences in reactivity may generalize to real-world situations. Evidence of
      significantly greater vasoconstriction during interviews about sad topics was
      also observed, contributing to the literature on the physiological
      differentiation of emotional states.

PMID- 9545663
TI  - Steady-state visual evoked potentials to computer monitor flicker.
AB  - In the present study, steady-state visual evoked potentials (S-VEP) in response
      to amplitude-modulated light from a computer monitor (colour sVGA, 15-inch tube)
      have been examined. S-VEPs to computer monitors with different refresh rates (60
      Hz or 72 Hz) and screen brightness (65 cd/m2 or 6 cd/m2) were recorded in 13
      subjects with normal or corrected-to-normal vision. EEG samples were amplified,
      averaged and stored using Cadwell Excel EMG-EP recorder and a regression model
      was applied for the amplitude analysis. The mean values of S-VEP amplitude at 60
      Hz were found to be significantly higher at 60 Hz refresh rate vs. 72 Hz (F1,12 =
      14.1; P = 0.003). Effect of screen brightness (F2,24 = 6.5; e = 0.62; P =
      0.00075) as well as the interaction effect of refresh rate and screen brightness
      (F2,24 = 11.6; P = 0.0003) were also found to be significant. Data obtained show
      that the characteristics of amplitude-modulated light from a computer monitor
      (frequency, brightness, waveform) are sufficient to elicit S-VEP, and the
      influence is not only restricted to the peripheral divisions of the visual system
      as it was shown earlier, but also extends to the central brain structures.

PMID- 9545662
TI  - Cardiac response induced by voluntary self-paced finger movement.
AB  - Cardiac responses induced by slow and brisk voluntary self-paced index finger
      movements of the dominant and non-dominant hand were investigated in a group of
      12 right-handed subjects. Since subjects synchronised movement and respiration,
      initiating movement preferably during inspiration, a novel method of evaluating
      the movement-induced cardiac response was used. This method allows one to
      distinguish the differential effects on the cardiac response due to movement and
      respiration. The effect of type of movements (slow vs. brisk) and hand (right vs.
      left) were analysed. Slow movements induced a monophasic cardiac response,
      consisting of cardiac deceleration preceding and accompanying movement. Brisk
      movements induced a biphasic cardiac response, consisting of preparatory
      deceleration followed by slight post-movement cardiac acceleration. Hand
      dominance did not influence the movement-induced cardiac response. The results
      suggest that neocortical structures involved in planning and execution of
      voluntary movement impinge upon brainstem cardiovascular nuclei. Vagal cardiac
      outflow is affected and gives rise to movement-induced changes in cardiac
      chronotropism.

PMID- 9545664
TI  - Physiological responses in high-P subjects during active and passive coping.
AB  - There have been relatively few studies of the psychophysiological correlates of
      Eysenck's dimension of psychoticism (P) and those which do not exist report
      findings which cannot be readily integrated to isolate a distinctive
      physiological basis of P. The present study investigated differences between
      subjects scoring high and low on the P scale of the Eysenck Personality
      Questionnaire (EPQ) in relation to sympathetic and parasympathetic arousal
      following aversive stimulation. An active-passive coping paradigm using an
      aversive tone was selected to elicit responses and cardiovascular measures (heart
      period, heart period variance, T-wave amplitude) and a skin conductance measure
      (event-related skin conductance) were obtained. The findings show that
      differences between high- and low-P subjects are specific to the coping
      condition. Under active coping, high-P subjects exhibited greater sympathetic
      arousal following the aversive tone than low-P subjects. There was no significant
      difference between the high-P and low-P subjects on any physiological variable
      under the passive coping condition. It is suggested that if there is differential
      functioning of the divisions of the autonomic nervous system in subjects
      differing in P, that these differences may only manifest themselves under
      specific situations.

PMID- 9545666
TI  - Intracranial recording during hypnotic analgesia.

PMID- 9545665
TI  - Effects of memory load on event-related patterns of 40-Hz EEG during cognitive
      and motor tasks.
AB  - The present study describes a phasic event-related synchronization (ERS) in the
      gamma band (36-44 Hz) induced by the onset of probe visual stimuli. The
      experiment consisted of two experimental tasks with high and low memory-load in
      which a geometrical figure (S1) was held in memory for comparison with a
      subsequent stimulus (S2). In each task a Go-NoGo paradigm was used with a Same
      Different discrimination task. The aim of the study was to examine the influence
      on 40-Hz ERS of stimulus type ('Same-Different') and of response (Go-NoGo) task
      as moderated by activation or effort level (high/low memory-load). The
      investigation was carried out in 27 women. The EEG was recorded from FP1, FP2,
      F3, F4, P3, P4, O1 and O2 scalp sites referenced to linked earlobes. As a
      manipulation check for activation level, we recorded heart rate (HR) during the
      S1-S2 period. A main peak of activity was found around 160 ms with a maximum at
      occipital sites. The amplitude of this peak was higher in the high memory-load as
      compared to the low memory-load condition. This difference was manifested mainly
      at F3 and O2 scalp sites. A larger 40-Hz peak at F3 was also found in the Go
      compared to the NoGo condition. No 40-Hz ERS differences between Same and
      Different trials were observed. The HR was found sensitive to the stimulus type
      showing a greater HR deceleration response to S2 for Same trials, as compared to
      Different ones. In parallel with 40-Hz ERS response, the HR deceleration was more
      pronounced for the high memory-load as compared to the low memory-load condition.
      The results indicate that the 40-Hz ERS is dependent upon both memory-load and
      motor responding. The influence of memory load on cognitive (Same-Different) and
      motor response (Go-NoGo) variables is discussed.

PMID- 9545667
TI  - [Effects of dosing regimen on the effectiveness and safety of aminoglycosides
      (discussion)].

PMID- 9545668
TI  - [The in vitro antibacterial activity of cefozopran against clinically isolated
      bacteria].
AB  - The in vitro antibacterial activity of cefozopran (CZOP) against recent clinical
      isolates was evaluated and compared with those of ceftazidime (CAZ), cefpirome
      (CPR), cefepime (CFPM), cefotaxime (CTX), sulbactam/cefoperazone (S/C), imipenem
      (IPM), oxacillin (MPIPC), and flomoxef (FMOX). MIC80 values of CZOP for
      methicillin-susceptible Staphylococcus aureus (MSSA, n = 41), methicillin
      resistant Staphylococcus aureus (MRSA, n = 57), Streptococcus pneumoniae (n =
      45), Enterococus faecalis (n = 49), Enterobacter cloacae (n = 50), Citrobacter
      freundii (n = 45), Serratia marcescens (n = 45), and Pseudomonas aeruginosa (n =
      100) were 1, 32, 2, 16, 4, 1, 0.25, 8 micrograms/ml, respectively. CZOP was more
      active than CPR against P. aeruginosa and exhibited similar activity to CPR
      against other species. CZOP was especially active against S. marcescens with MIC
      values lower than 1 microgram/ml against all strains tested. CZOP was similarly
      active to or more active than CFPM against all species except for C. freundii.
      CZOP was not active against MRSA. Thus, we investigated the in vitro combination
      effects of CZOP/vancomycin (VCM) and CZOP/arbekacin (ABK) using the checkerboard
      method. The interaction between CZOP and VCM ranged from additive activity (0.5 <
      FIC index < or = 1.00, n = 37) to synergistic activity (FIC index < 0.50, n = 1),
      except for one strain showing indifference (1.00 < FIC index < or = 2.00). The
      interaction between CZOP and ABK ranged from additive activity (n = 22) to
      synergistic activity (n = 1). These date suggest the potential effect of
      combination therapy of (CZOP) and VCM or ABK against MRSA. The combined therapy
      is suggested to be useful to reduce side effects in patients with impared renal
      function, to reduce the administration dose of VCM or to treat infections of
      sites where achievable drug concentrations are lower than those commonly achieved
      in the bloodstream. We also investigated the combination effects of CZOP/AMK and
      CZOP/GM against CZOP-resistant P. aeruginosa (MIC > 16 micrograms/ml). The
      combination of CZOP/AMK showed additive activity (n = 9) to synergistic activity
      (n = 2). The combination of CZOP/GM showed additive activity (n = 5). These
      results suggest that combinations of CZOP with AMK or GM are effective in
      treating P. aeruginosa.

PMID- 9545669
TI  - [Fundamental and clinical evaluation of cefozopran in low birth weight infants
      and neonates].
AB  - We conducted fundamental and clinical evaluations of a cephem antibiotic,
      cefozopran (SCE-2787, CZOP), in infants with low birth weights and mature
      infants. (1) Blood concentrations CZOP was intravenously given in bolus dose of
      20 mg/kg to the newborn. The blood antibiotic concentrations were 69.7
      micrograms/ml at 30 minutes after administration and the elimination half life
      was 2.99 hours in mature infants aged 1 to 3 days. They were 38.7 micrograms/ml
      and 2.85 hours in those aged 4 to 7 days, and 40.8 micrograms/ml and 3.81 hours
      in those aged 8 days or elder, respectively. In infants with lower birth weights
      aged 4 to 7 days the blood antibiotic concentrations were 48.6 micrograms/ml at
      30 minutes after i.v. administration and the elimination half life was 3.77
      hours. The blood antibiotic concentrations at 30 minutes after intravenous doses
      of 10, 20 and 50 mg/kg in mature infants aged 8 days or elder were 21.1, 40.8 and
      153.6 micrograms/ml (value at 60 minutes) and the elimination half lives were
      2.24, 3.81 and 3.07 hours, respectively. Administration of CZOP at doses of 20
      and 40 mg/kg by intravenous drip infusion over 30 minutes gave the blood drug
      concentrations of 48.0 and 103.2 micrograms/ml at the end of the infusion and the
      half lives were 2.60 and 3.33 hours, respectively. (2) Urinary excretion The
      urinary excretion rates after i.v. bolus doses of 10, 20 and 40 mg/kg were 28.4
      to 58.6% of dose. The urinary excretion rate after i.v. drip infusion of 40 mg/kg
      over 30 minutes was 49.0% of dose. (3) Transfer into cereblospinal fluid The
      transfer of the antibiotic into cereblospinal fluid in patients with serous
      meningitis was 4.1 to 15.5 micrograms/ml at 1 hours after administration. (4)
      Clinical results The clinical efficacy was judged "good" or "excellent" in 2 of
      the 3 patients with septicemia and in all of the 10 patients with suspected
      septicemia. It was judged "excellent" in all of the 9 patients with pneumonia, 3
      with urinary tract infections and 3 with intrauterine infections. Prophylactic
      use of the antibiotic was effective in all of the 12 patients. Of the patients in
      whom bacteriological evaluation was successful, 7 of the 10 causative organisms
      were confirmed to be eradicated. No adverse drug reactions of signs and symptoms
      were recognized. Fourteen abnormal alterations of the laboratory test values such
      as elevation of gamma-GTP and that of GPT were recognized in 8 patients (16.7%).
      None of them were particularly serious. These results indicate that CZOP is a
      drug useful for treatment and prevention of infections in infants with lower
      birth weights as well as in mature infants.

PMID- 9545670
TI  - [Pharmacokinetic, bacteriological and clinical studies on cefozopran in
      neonates].
AB  - Cefozopran (CZOP) was administered to nine newborn patients with infections at a
      dose of 20 mg/kg twice or three times daily for 5 to 6 days to evaluate the
      efficacy, safety and pharmacokinetics of cefozopran. 1. Blood concentrations CZOP
      was intravenously given to 6 newborn patients by drip infusion at a dose of 20
      mg/kg over 30 minutes. The maximum blood concentrations (Cmax) were 38.4
      micrograms/ml in a patient aged 0 day, 37.7 and 54.3 micrograms/ml in two
      patients aged 1 day, 51.3 and 64.1 micrograms/ml in two patients aged 3 days and
      51.0 micrograms/ml in a patient aged 5 days. Cmax was lower in the patient aged 0
      day. The elimination half life (T 1/2) was 9.2 hours in the patient aged 0 day,
      4.9 and 3.7 hours in the patients aged 1 day, 3.1 and 2.4 hours in the patients
      aged 3 days and 2.9 in the patient aged 5 days, showing a prolongation of T 1/2
      in patients of lower age. 2. Urinary excretion Of the 6 patients given CZOP at a
      dose of 20 mg/kg by intravenous drip infusion over 30 minutes, urine was
      collected in 5 patients. The cumulative excretion rate within 6 hours after
      infusion was as low as 19.8% of dose in the patient aged 0 day. The rates were
      elevated as high as 46.3 and 57.0% of dose in the patients aged 1 day. In the
      patient aged 3 days, the recovery within 4 hours after infusion was 47.3%. It was
      70.6% of dose within 6 hours after dosing in the patient aged 5 days. The urinary
      recovery within 6 hours after dosing increased with the advance of age. 3.
      Clinical results Efficacy was evaluable in 7 patients. Of them, 3 had suspected
      septicemia, 2 pneumonia, 1 intrauterine infection and 1 urinary tract infection.
      The clinical efficacy was judged "excellent" in all the evaluable patients.
      Neither adverse drug reactions of signs and symptoms nor abnormal alterations of
      the laboratory test values were recognized in the 9 patients evaluable for
      safety. These results suggest that CZOP is an effective and safe drug for
      treatment of infections in the newborns. As for the dosage and method of
      administration from the view of the pharmacokinetic data obtained, intravenous
      drip infusion of 20 mg/kg once or twice daily was considered to be sufficient for
      patients aged 0 day. For patients aged 1 to 7 days and those aged 8 days or
      elder, the administration of twice to 3 times daily and 3 to 4 times daily were
      considered to be sufficient, respectively.

PMID- 9545671
TI  - [Pharmacokinetic, bacteriological and clinical studies on cefozopran in
      neonates].
AB  - The efficacy, safety and pharmacokinetics of cefozopran (CZOP) were evaluated in
      neonates and the following results were obtained: 1. Of the 12 patients treated
      with CZOP, judgment of clinical efficacy was evaluable in 10 patients (including
      5 with pneumonia and 3 with urinary tract infections). The treatment was
      effective and the causative organism was eradicated in 100% of the patients. 2.
      No adverse signs and symptoms were recognized during the treatment with CZOP. A
      slight elevation of direct bilirubin was recognized as an abnormal alteration of
      laboratory test values in one patient. The value, however, returned to the normal
      range after the completion of treatment. 3. The pharmacokinetic evaluation was
      made in 3 of the 12 patients. The blood CZOP levels were recognized in proportion
      with the dosages. The elimination half lives (T 1/2) in those patients were 8.92,
      2.90 and 2.76 hours. Prolongation of T 1/2 was recognized in the patient aged 0
      day. It was possible to examine the urinary excretion only in one patient aged 18
      days. The excretion rate of the drug was 68.6% of dose by 8 hours after
      administration. These results suggest that CZOP is a drug useful for treatment of
      infections in neonates as well, with high efficacy and safety.

PMID- 9545672
TI  - [Pharmacokinetic and clinical evaluation of cefozopran in premature and newborn
      patients].
AB  - Cefozopran (SCE-2787, CZOP), which is already on the market with a variety of
      approved indications in infectious diseases for adult patients, was administered
      to premature and newborn patients to evaluate the pharmacokinetics and the
      clinical efficacy. 1. Pharmacokinetics CZOP was intravenously administered at
      doses of 10.0 mg/kg, 21.4 mg/kg and 40.0 mg/kg to premature and newborn patients,
      and the blood concentrations and urinary excretion rate were examined. The blood
      CZOP concentrations were 31.7 and 65.5 micrograms/ml at 30 minutes after
      administration of 10.0 mg/kg and 40.0 mg/kg, respectively. The elimination half
      life was 1.78 hours and 2.31 hours, and the urinary recovery was 110.7% and 53.7%
      within 6 hours after administration, respectively. In the patient given 21.4
      mg/kg, the blood CZOP concentration was 36.4 mg/kg at 1 an hour after
      administration and the elimination half life was 3.97 hours. The urinary recovery
      was 29.6% within 5 hours after administration. 2. Clinical results The clinical
      efficacy was evaluated in 19 patients and judged "good" or better in 13 of them
      with the efficacy rate or 68.4%. The bacteriological response was evaluated in 10
      patients from whom Gram-positive cocci of S. aureus (6 strains), S. pneumoniae (1
      strain) and E. faecalis (1 strain) and Gram-negative bacilli of H. influenzae (2
      strains) and E. coli (2 strains) were isolated as possible causative organisms.
      With exception of 1 strain each of S aureus and H influenzae, which were not
      tested after the treatment with CZOP, all of these strains were found to be
      eradicated. 3. Adverse drug reactions (ADRs) of signs and symptoms and abnormal
      alterations of laboratory test values. Safety evaluation was made in 24 patients.
      ADRs of signs and symptoms were recognized in none of them. As abnormal
      alterations of laboratory test values, increased eosinophils in 3 patients,
      elevated GOT in one and elevated GPT in one were recognized. These results
      indicate that CZOP is a drug useful for treatment of infections in premature and
      newborn patients.

PMID- 9545673
TI  - [Pharmacokinetic and clinical evaluation of cefozopran in newborn patients].
AB  - Pharmacokinetic and clinical evaluation of an injectable cephem antibiotics,
      cefozopran (SCE-2787, CZOP), was conducted in newborn patients and the following
      results were obtained: 1. Clinical results The clinical efficacy of CZOP was
      evaluated in one each patient with intrauterine infection and suspected
      septicemia. The efficacy was "excellent" in both patients. No clinically serious
      adverse drug reactions of signs and symptoms and abnormal alterations of the
      laboratory test values were recognized. 2. Pharmacokinetics CZOP was
      intravenously given to newborn patients at doses of 25.0, 20.0, and 18.75 mg/kg.
      The blood CZOP concentrations were 44.7 +/- 7.0 micrograms/ml (n = 3), 48.3
      micrograms/ml and 48.2 micrograms/ml at one hour after administration,
      respectively. The elimination half life (T 1/2) was 4.22 +/- 1.17 hours (n = 3)
      in the patients given 25.0 mg/kg and 2.74 hours in the patient given 20.0 mg/kg.
      The urinary drug excretion rate was 44.5 +/- 8.7% and 31.3 +/- 9.7% of dose
      within 8 hours after administration of 25.0 mg/kg and 20.0 mg/kg, respectively.

PMID- 9545674
TI  - Tactile sensitivity of gloved hands in the cold operation.
AB  - In this study, tactile sensitivity of gloved hand in the cold operation has been
      investigated. The relations among physical properties of protective gloves and
      hand tactile sensitivity and cold protection were also analysed both objectively
      and subjectively. Subjects with various gloves participated in the experimental
      study during cold exposure at different ambient temperatures of -12 degrees C and
      -25 degrees C. Tactual performance was measured using an identification task with
      various sizes of objects over the percentage of misjudgment. Forearm, hand and
      finger skin temperatures were also recorded throughout. The experimental data
      were analysed using analysis of variance (ANOVA) model and the Tukey's multiple
      range test. The results obtained indicated that the tactual performance was
      affected both by gloves and by hands/fingers cooling. Effect of object size on
      the tactile discrimination was significant and the misjudgment increased when
      similar sizes of objects were identified, especially at -25 degrees C.

PMID- 9545675
TI  - Control of liquid cooling garments: technical control of mean skin temperature
      and its adjustments to exercise.
AB  - This paper describes an automatic control concept for liquid cooling garments.
      The concept consists of an own controller for mean skin temperature whose
      setpoint is either fixed or adjusted to the metabolic heat production by means of
      the heart rate signal. The controller for mean skin temperature included both a
      proportional and an integral signal path (PI-type), the latter being able to
      eliminate any load error within the control loop. This means that the actual skin
      temperature will always match the given setpoint irrespective of the amount and
      the origin of the heat gain at the body shell. Experiments were carried out to
      test the operation of the skin temperature controller. There the setpoint was
      fixed while metabolic heat production was changing. After a transient period with
      deviations, the load error was always eliminated by the skin temperature
      controller. With this result one can also imagine the controllers ability to
      compensate changing heat gains from the environment. Despite this behaviour, the
      amount of heat removal was not high enough to prevent sweating and warm
      discomfort during all exercise levels. Therefore we draw the conclusion that, in
      addition, the setpoint of the skin temperature should be adjusted to the
      metabolic rate/heat production. A convenient physiological signal that reflects
      the current level of metabolic rate is the heart rate signal. After being
      filtered the heart rate signal was used during some experiments to change the
      setpoint of the skin temperature controller. The reason for this filtering
      (lowpass, time constant = 10 min) was, firstly, the necessity of attenuating the
      consequences of short-term psychological effects on the heart rate and secondly,
      the avoidance of vasoconstriction due to too fast changes of the exercise/heart
      rate induced cooling rate. In the following experiments it became clear that the
      adjustment of the skin temperature setpoint to the exercise level was an
      improvement as there was less sweating and the subjects felt more comfortable.

PMID- 9545676
TI  - Blood lactate disappearance during breathing hyperoxic gas after exercise in two
      different physical fitness groups--on the work load fixed at 70% VO2max.
AB  - The purpose of this study is to evaluate effects of breathing hyperoxic gas on
      blood lactate disappearance after submaximal exercise in two different physical
      fitness groups and to clarify the most effective oxygen concentration in each
      group. Fourteen healthy male students participated as subjects in this study.
      They were divided in two groups by difference in their anaerobic threshold (AT).
      Seven males were treated as Higher AT group and the others as Lower AT group.
      Subjects wore a T-shirt, short pants and sports shoes and performed three
      sessions; each consisting of five minutes of exercise and six minutes of rest, at
      a workload of 70%VO2max on a bicycle ergometer. Hyperoxic gas was breathed only
      during recovery periods. Oxygen rates of 21, 30, 40, 60, 80 and 100% in inspired
      gas were employed. According to the results of blood lactate (BLA), the most
      effective oxygen condition on BLA disappearance was obtained over 60% in Higher
      AT group and at 30% oxygen in Lower AT group. Thus, it was especially noteworthy
      that the effects of hyperoxic gas in Higher AT group were different from those of
      Lower AT group. It is thought that the effects of breathing hyperoxic gas were
      dependent on physical fitness, which have caused many reports to be in conflict
      hitherto.

PMID- 9545677
TI  - Physical fitness and psychological benefits of strength training in community
      dwelling older adults.
AB  - Previous studies concerning psychological benefits of exercise among the elderly
      has focused predominantly on the effects of aerobic exercise. In the present
      study, psychological and behavioral adaptations in response to 12-weeks of
      strength training were examined in medically healthy but sedentary 42 older
      adults (mean age = 68 years). The purpose of this study was to evaluate the
      effects of high and low intensity resistance training intensity on a) muscular
      fitness, b) psychological affect, and c) neurocognitive functioning. Subjects
      were randomly assigned to high intensity/low volume (EXH: 2 sets of 8 to 10
      repetitions for 75 to 85% of 1 RM), low intensity/high volume (EXL: 2 sets of 14
      to 16 repetitions for 55 to 65% of 1 RM), or no exercise control programs. Prior
      to and following the 12-week program, subjects underwent comprehensive
      physiological and psychological evaluations. Physiological assessment included
      measurements of blood pressure, heart rate, arm and leg muscle strength, body
      composition, and oxygen consumption (VO2max). Psychological measures included
      evaluations of mood, anxiety, and physical self-efficacy as well as cognitive
      functioning. The results of this study indicated that both high and low intensity
      strength programs were associated with marked improvements in physiological
      fitness and psychological functioning. Specifically, subjects in the strength
      training programs increased overall muscle strength by 38.6% and reduced percent
      body fat by 3.0%. Favorable psychological changes in the strength-trained
      subjects included improvements in positive and negative mood, trait anxiety, and
      perceived confidence for physical capability. The treatment effects of
      neurocognitive functioning were not significant. In summary, this study
      demonstrated that participation in 12-weeks of high or low intensity strength
      training can improve overall physical fitness, mood, and physical self-efficacy
      in older adults while cognitive functioning remains constant.

PMID- 9545678
TI  - [Clinical usefulness of scatter and attenuation correction for brain single
      photon emission computed tomography (SPECT) in pediatrics].
AB  - This investigation was undertaken to study clinical usefulness of scatter and
      attenuation correction (SAC) of brain SPECT in infants to compare the standard
      reconstruction (STD). The brain SPECT was performed in 31 patients with 19
      epilepsy, 5 cerebro-vascular disease, 2 brain tumor, 3 meningitis, 1
      hydrocephalus and psychosis (mean age 5.0 +/- 4.9 years old). Many patients was
      necessary to be injected sedatives for restraining body motion after Technetium
      99m hexamethylpropylene amine oxime (99mTc-HMPAO) was injected at the convulsion
      or rest. Brain SPECT data were acquired with triple detector gamma camera (GCA
      9300 Toshiba Japan). These data were reconstructed by filtered backprojection
      after the raw data were corrected by triple energy windows method of scatter
      correction and Chang filtered method of attenuation correction. The same data was
      reconstructed by filtered backprojection without these corrections. Both SAC and
      STD SPECT images were analyzed by the visual interpretation. The uptake ratio of
      cerebral basal nuclei was calculated by the counts of the thalamus or lenticular
      nuclei divided by the cortex. All images of SAC method were excellent than that
      of STD method. The thalamic uptake ratio in SAC method was higher than that of
      STD method (1.22 +/- 0.09 > 0.87 +/- 0.22 p < 0.01). The lenticular nuclear
      uptake ratio in SAC method was higher than that of STD method (1.26 +/- 0.15 >
      1.02 +/- 0.16 p < 0.01). Transmission scan is the most suitable method of
      absorption correction. But the transmission scan is not adequate for examination
      of children, because this scan needs a lot of time and the infants are exposed by
      the line source radioisotope. It was concluded that these scatter and absorption
      corrections were most suitable method for brain SPECT in pediatrics.

PMID- 9545680
TI  - [Simplified method to quantitate regional cerebral blood flow by 123I-IMP
      microsphere model: validity of input counts by using the whole brain time
      activity curve and one point arterial blood sampling].
AB  - We developed a new microsphere method using 123I-IMP in which arterial blood is
      collected at one time point early after 123I-IMP injection instead of
      conventional continuous arterial blood sampling, and the input count is estimated
      using a whole brain time-activity curve until that time point. The differential
      curve dCb(t)/dt of the brain time-activity curve Cb(t) early after 123I-IMP
      injection (when the microsphere model is established) approximates the arterial
      time-activity curve Ca(t) as an input function. The input count as the integral
      value of Ca(t) at 0-5 min was estimated using the 50 min whole brain activity
      Cb(5 min) and the differential value dCb(5 min/dt and the 5-min octanol-extracted
      count of arterial samples obtained at one time point Ca(5 min). The input counts
      calculated by this method were very closely correlated with measurement values
      obtained by continuous arterial sampling. This method is more convenient and less
      invasive than the continuous arterial sampling method.

PMID- 9545679
TI  - [Estimation of integral value of input function for the quantification of
      cerebral blood flow with 123I-IMP using one-point arterial blood sampling].
AB  - Cerebral blood flow (CBF) has been measured using a microsphere model with
      octanol-extracted radioactivity counts (integral value of input function). We
      developed a new method estimating the integral value of input function. First, we
      fitted the whole brain time-activity curves early after intravenous injection of
      N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) by the least-squares method.
      Second, we differentiated this equation. Third, we calibrated it using octanol
      extracted radioactivity counts of the arterial blood sampled at 5 min. Finally,
      we integrated it. A significant correlation was found between the integral values
      obtained using a new method and those obtained using the continuous arterial
      blood sampling data (y = 1.048x-1206, r = 0.984). The errors between the CBF
      values obtained using a new method and those obtained using the 5-min continuous
      arterial blood sampling was 6.88 +/- 4.78%. Measurement of integral values of the
      input function using a new method with one-point arterial blood sampling is less
      invasive and convenient, and is not influenced by cardiopulmonary disease or
      smoking. Therefore, it would be useful for the routine measurement of CBF.

PMID- 9545682
TI  - [Analysis of cerebral blood flow SPECT imaging on standard brain atlas in
      patients with dementia of Alzheimer type].
AB  - Statistical parametric map (SPM) has been developed by Friston et al. to analyze
      focal changes in rCBF induced by brain activation. This automated and objective
      approach has the potential of being applied to SPECT image data sets. This study
      evaluated an automated analysis of brain SPECT imaging in patients with dementia
      of Alzheimer type (DAT) using SPM95. Seventeen patients with clinically diagnosed
      moderate to severe DAT and nine normal control subjects were studied. The SPECT
      device used was a triple-headed rotation gamma camera GCA9300A/HG. All images
      were transformed into the standard anatomical space of the stereotactic brain
      atlas of Talairach and Tournoux, and then smoothed. Statistical analysis was made
      between DAT and normal control groups. SPM analysis of SPECT images revealed that
      the parieto-temporal areas and posterior cingulate gyrus of both cerebral
      hemispheres were significantly decreased in DAT patients compared to normal
      controls. In conclusion, SPM analysis of SPECT images proved to be useful in the
      evaluation of abnormal perfusion areas of demented patients.

PMID- 9545681
TI  - [Cardiac sympathetic denervation after aortic surgery in a patient with thoracic
      dissecting aneurysm: a case report].
AB  - We experienced a case of a 60 year-old man with cardiac sympathetic denervation
      after aortic graft replacement of ascending aorta for a dissecting aneurysm
      (Debakey type II). Fourteen years after pheochromocytomectomy (paraganglioma),
      the patient developed a severe chest pain, and admitted to the hospital for the
      diagnosis of dissecting aneurysm. CT scan with contrast enhancement revealed
      thrombosed dissecting aneurysm in the region of ascending aorta to aortic arch.
      Graft replacement was undergone on the same day. 123I-MIBG imaging 20 days after
      the operation showed severely attenuated myocardial uptake (heart to mediastinum
      ratio 1.19), although the MIBG imaging before the operation showed normal
      myocardial uptake (heart to mediastinum ratio 1.55). Heart rate variability
      analysis in Holter ECG showed that the power of the low frequency (LF), that of
      the high frequency (HF) and L/H ratio were severely decreased. MIBG and heart
      rate variability analysis indicated that cardiac sympathetic and parasympathetic
      nerve were denervated. This is the first report of cardiac sympathetic
      denervation after aortic vascular surgery. Clinical significance of cardiac
      sympathetic denervation after aortic vascular surgery is uncertain, and further
      investigation will be required.

PMID- 9545683
TI  - [Enterohemorrhagic Escherichia coli O157 outbreak in Obihiro-City--study on
      antibiotic susceptivity and plasmid profiles].
AB  - The drug-resistance patterns and plasmid profiles of 147 isolates (patient origin
      142 and food origin 5 isolates) from the outbreak of enterohemorrhagic
      Escherichia coli (EHEC) O157:H7 infection in Obihiro-city Hokkaido in late
      October, 1996, were examined. Thirty-six isolates were resistant to tetracycline
      (TC) (24.5%), 15 of which were resistant to both streptomycin and TC. The minimal
      growth inhibitory concentration (MIC) of fosfomycine (FOM) was examined,
      confirming that MIC changed by the cultivation conditions, that is 12.5
      micrograms/ml at the aerobic condition, 1.6 micrograms/ml at the anaerobic
      condition and 3.2 micrograms/ml on blood agar plates. Furthermore, though E. coli
      O157 could not be detected once by the FOM medication, FOM sensitivity of the
      patient origin O157 isolates who became O157-positive again was examined. Any
      changes in FOM sensitivity were not observed. Plasmid profiles of all isolates
      were divided by 4 patterns from A to D. The most dominant pattern was type A, and
      plasmid profiles of food origin O157 belonged to pattern A. In 9 examples of the
      person-to-person infection in the family, plasmid patterns of O157 isolates were
      the same to each other, even though drug-resistant patterns were different. In 13
      patients developing the duration of excretion of EHEC, the changes of the drug
      resistance patterns were correlated with the changes of plasmid profiles. By
      comparing plasmid profiles and TC resistance, it was suggested that TC resistance
      was controlled on a plasmid. Since food origin O157 isolates were sensitive to
      all drugs and presenting the same plasmid profiles, demonstrating that TC
      resistance and plasmid are newly added to the bacterial cells while food origin
      O157 isolates passe inside the human body.

PMID- 9545684
TI  - [Ionic binding of 3H-gentamicin and short-term bactericidal activity of
      gentamicin against Pseudomonas aeruginosa isolates differing in
      lipopolysaccharide structure].
AB  - The clinical isolates of Pseudomonas aeruginosa can be roughly classified into
      long- and short-lipopolysaccharide (LPS) strains and LPS-deficient strains, based
      on the silver-stained patterns of their LPSs after SDS-PAGE. The ionic binding of
      3H-gentamicin, a polycationic antibiotic, to the negatively charged sites on the
      surface structures of P. aeruginosa strains, often differing in LPS structure,
      was the highest in the long-LPS strains followed in descending order by the short
      LPS strains and LPS-deficient strains. It was presumed that a clinical isolate of
      P. aeruginosa No. 45 is lacking in the O-polysaccharide chains and some
      structures of the core-regions consisting of its LPS-structure after SDS-PAGE. On
      the other hand, the binding of 3H-gentamicin to this strain was quite. high,
      i.e., similar to that to of the long-LPS strains. To clarify this finding, P.
      aeruginosa PAC1R and its LPS-deficient mutants were used as reference strains
      because the chemical structures of their LPSs containing the repeated units of O
      polysaccharides and the neutral sugar contents in the core-regions were
      previously confirmed. The PAC605 strain of the LPS-mutants of the PAC series, was
      completely lacking in the repeated units of O-polysaccharide and also lacking in
      some neutral sugar residues of the core-oligosaccharide region. However, this
      strain was highly bound to 3H-gentamicin, suggesting that the negatively charged
      sites on the deep core-oligosaccharide region and/or on lipid A participated in
      the binding of 3H-gentamicin. This manner of binding may be also applied to P.
      aeruginosa No. 45. When P. aeruginosa PAC1R, PAC605 and No. 45 strains were each
      exposed to gentamicin (20 micrograms/ml) for 10 minutes, the viable cell counts
      of PAC1R decreased to about 70% of the initial count, whereas the viable cell
      counts of PAC605 and No. 45 strains decreased to 3.6 and 11.0% respectively,
      indicating the vulnerability of both types of the strains to be enhanced by the
      bactericidal action of gentamicin with short-term incubation.

PMID- 9545685
TI  - [Survey of fungemia cases during the past seventeen years at Teikyo University
      Hospital].
AB  - Fungi were isolated from 642 cases (3.5%) of 18,403 blood samples at Teikyo
      University Hospital during the 17-years period between 1979 and 1995. The number
      of fungemia cases began to increase around 1985, reached a peak in 1988, and
      since then, it has been gradually decreasing. The fungal species of isolates
      were: (1) Candida albicans in 224 cases (34.9%), (2) C. parapsilosis in 149 cases
      (23.2%), (3) C. tropicalis in 87 cases (13.6%), (4) C. glabrata in 65 cases
      (10.1%), (5) Hansenula anomala in 58 cases (9.0%), (6) C. guilliermondii in 24
      cases (3.7%), (7) C. famata in 14 cases (2.1%), (8) Trichosporon beigelii in 11
      cases (1.7%), (9) C. inconspicua in 5 cases (0.8%) and C. lusitaniae in 5 cases
      (0.8%), and other yeasts in 33 causes (5.1%). The number of isolates of C.
      albicans has been decreasing since 1989, concomitant with the clinical
      introduction of fluconazole in this hospital. However, the number of fluconazole
      insusceptible fungi such as non-albicans Candida and Trichosporon spp. has
      increased. Fungemia cases infected concomitantly or sequentially with two or more
      different fungal species have been found occasionally since 1983 and have shown a
      high mortality rate. The spectrum of the causative organisms of fungemia appears
      to be, at least, partly influenced, by the usage of antifungal agents,
      particularly fluconazole.

PMID- 9545686
TI  - Sensitive detection of Helicobacter pylori in gastric aspirates by polymerase
      chain reaction.
AB  - The detection of Helicobacter pylori in gastric aspirate was examined by using
      the polymerase chain reaction (PCR) method for amplifying a specific fragment of
      the urease gene A. The ability of PCR to amplify H. pylori-specific DNA was
      analyzed by Southern hybridization with an internal oligonucleotide probe. Twenty
      two H. pylori strains from clinical isolates and reference strains were studied,
      and all H. pylori strains yielded a 356-bp product that hybridized with the
      oligonucleotide probe, whereas no amplification was evident with 18 non-H. pylori
      strains. This could detect as little as 50 CFU of H. pylori in pure culture and
      0.1 pg of purified chromosomal DNA. A total of 50 dyspeptic patients were
      examined for the presence of H. pylori by culture, the rapid urease test and
      histological examination of antral biopsy samples as well as by PCR in gastric
      juice aspirate samples. The gold standard for the presence of H. pylori was
      established by minimum concordance of two of three tests performed on biopsy
      specimens. With this gold standard, 34 of the 50 patients were considered to
      harbor H. pylori infection. PCR correctly identified 32 (94.1%) of these 34
      infected patients. PCR had the best combination of sensitivity and specificity in
      assessing the correct diagnosis of H. pylori as compared with those of the rapid
      urease test and culture. Moreover, we established a fast and simple method for
      use by improvement of DNA extraction. PCR of the gastric aspirate was shown to be
      a sensitive and specific procedure which may be an attractive alternative to
      methods currently used for diagnosis of H. pylori infection.

PMID- 9545687
TI  - [Inflammatory reactions and microorganisms cultured from sputum and blood in
      association with terminal stage infection of patients with lung cancer].
AB  - We reviewed our experience with terminal stage infections in patients with lung
      cancer over an 11 year period at Kurume University Hospital. In patients with end
      stage lung cancer, the infection is common and a mortal disease. We examined the
      clinical features and significance of pathogenic microbes isolated from sputum
      and blood in patients with lung cancer during their last month. Bacteriological
      examinations from blood done frequently in patients with episodes of fever
      revealed that bacteremia was one of the most important disease in terminal stage
      infection. In the blood cultures from the 22 patients various species of
      pathogenic microbes were recovered, and nine of which were fungi; five Candida
      albicans, three Candida tropicalis and one Candida parapsilosis. The major
      species of bacteria isolated from sputum were Staphylococcus aureus, including
      methicillin-resistant strain, and Gram-negative bacilli; P. aeruginasa, A.
      calcoaceticus, K. pneumoniae and E. cloacae, which are known to be frequently
      involved in hospital-acquired infections. However, S. pneumoniae and H.
      influenzae which were well known to be microbes of respiratory infections were
      rare. We concluded that we had to reveal the feature of terminal stage infection
      in order to reduce the fee for medical treatment and improve the QOL of patients
      with terminal stage lung cancer.

PMID- 9545688
TI  - [Detection of intrathoracic infectious lesions using In-diethylenetriamine
      pentaacetic bicyclic anhydride-IgG (111In-DTPA-IgG) scintigraphy].
AB  - The utility of 111In-DTPA-IgG imaging for the detection of intrathoracic lesions
      was evaluated in 10 patients with the suspicion of inflammatory or infectious
      diseases. They were intravenously administered 40 or 80 MBq of 111In-DTPA-IgG,
      and scanned after 24 or 48 hours. Of these, 8 cases, consisted of 4 cases with
      pneumonia and 2 cases with lung abscess and one case of pulmonary tuberculosis
      and one of a tuberculous pleuritis, showed true positive results. Others were one
      false negative case of pneumonia and one true negative case of lung cancer.
      Overall sensitivity and specificity were 88.9% and 100%, respectively. There were
      no cases which showed side effects or abnormal laboratory findings caused by the
      radiopharmaceuticals administered. Thus, 111In-DTPA-IgG imaging is a useful tool
      for the detection of intrathoracic infectious lesions.

PMID- 9545689
TI  - [Detection of enterovirus 70 in acute hemorrhagic conjunctivitis by PCR-stringent
      microplate hybridization method].
AB  - The surveillance of acute hemorrhagic conjunctivitis (AHC) caused by enterovirus
      70 (EV70) is insufficient because of the difficulties of virus isolation using
      conventional methods. In this study, reverse transcription-polymerase chain
      reaction (RT-PCR) and stringent microplate hybridization (SMH) methods were
      assessed for the detection of EV70 in conjunctival swabs collected from the
      patients of AHC which broke out in Miyazaki Prefecture in 1990 and Okinawa
      Prefecture in 1994. Furthermore, with the use of the SMH method, we compared the
      genetic homogeneity of EV70 detected from the samples collected in 1990 and 1994
      to the J670/71 strain isolated approximately 25 years ago. A similar
      investigation was performed between recent coxsackievirus A24 variant (CA24v) and
      EH24/70 strain, a standard strain of CA24v that was isolated approximately 25
      years ago. As a result, RT-PCR products were detected in 26 of 34 conjunctival
      swabs collected in Miyazaki Prefecture in 1990. Likewise, RT-PCR products were
      detected in 9 of 10 conjunctival swabs collected in Okinawa Prefecture in 1994,
      and these RT-PCR products were all identified as EV70 by SMH method. Such a high
      level of virus recovery from specimen shows the evidence of usefulness of these
      techniques. Recent EV70 showed a reaction of about 60% to a probe synthesized
      with J670/71. Likewise, recent CA24v showed a reaction of about 30% to a probe
      synthesized with EH24/70. These finding are highly suggestive of the progress of
      viral mutation.

PMID- 9545690
TI  - [Acute respiratory distress syndrome complicating imported Plasmodium falciparum
      malaria].
AB  - A 25-year-old male, who had returned from the Republic of Mali in Africa, was
      admitted to our hospital because of a 3-day history of high fever, on the first
      of October 1996. He was diagnosed as Plasmodium falciparum malaria by peripheral
      blood smear. From the admission day he was treated with quinine HCL, 1,500 mg per
      day, and sulfamethoxazole 2,400 mg trimethoprim 480 mg per day, but on October
      2nd blood examination showed 35% parasite density and he was given mefloquine.
      However he was complicated with DIC on October 3rd, ARDS on October 5th. By anti
      coagulant therapy and methylprednisolone pulse therapy he became afebrile and
      respiratory function improved rapidly. ARDS should be emphasized as a severe
      complication of imported severe malaria.

PMID- 9545691
TI  - [A case of tuberculous pyothorax after an interval of four years of finishing
      with the first treatment for pulmonary tuberculosis].
AB  - We reported a case of tuberculous pyothorax which developed at four years after
      finishing with the first treatment for pulmonary tuberculosis. A 50-year-old
      female was admitted to our hospital with right chest pain. Tuberculous pyothorax
      was diagnosed by means of polymerase chain reaction (PCR method) of pleural
      effusion and of histological findings of the pleural section. She was cured by
      operation, pleural drainage and anti-tuberculous drugs. The bone scincigram of
      99mTc revealed accumulation in the right 9th rib, tuberculous empyema might have
      been a secondary development from osteomyelitis.

PMID- 9545692
TI  - Severe malaria from a new beach resort.

PMID- 9545693
TI  - [Retropharyngeal abscess in an adult and an elderly woman].
AB  - Retropharyngeal abscess is reported to be decreasing in frequency in recent
      years. We report two cases of retropharyngeal abscess that were diagnosed within
      four years in Department of Otorhinolaryngology, Gifu University Hospital. Case 1
      was a 36-year-old male who was suggested to have an abscess as primary infection
      and case 2 was a 71-year-old female whose abscess seemed to be a secondary
      infection following unknown primary infection. Endoscopic or open neck drainage
      as well as antibacterial chemotherapy mainly with combinations of flomoxef and
      clindamycin in the case 1 and piperacillin and clindamycin in the case 2 was
      successfully carried out. They were discharged an 15-day and 24-day after
      operation in the cases 1 and 2, respectively. A 30 min. culture after sample
      collection on operation demonstrated aerobe-anaerobe mixed infection in both
      cases; three aerobes and four anaerobes in the case 1 and three aerobes and two
      anaerobes in the case 2. These results suggest that retropharyngeal abscess may
      be a complicated infection involving more bacterial species than has been
      commonly believed. Measuring susceptibility of isolates to antimicrobial agents,
      a strain of Capnocytophaga sp. and a strain of anaerobic gram-negative rod were
      highly resistant to piperacillin, cefroxine and ofloxacin. It is important for
      adequate antibacterial chemotherapy to grasp the bacteriology of retropharyngeal
      abscess and analyze susceptibility of antimicrobial agents.

PMID- 9545694
TI  - Hemolytic uremic syndrome in a patient with Bacteroides fragilis infection.

PMID- 9545695
TI  - [Carrier state of escherichia coli O157:H7 in cattle].

PMID- 9545696
TI  - [Usefulness of MycoDot test for the detection of anti-mycobacterial antibodies as
      an aid in the diagnosis of experimental Mycobacterium tuberculosis and
      Mycobacterium avium complex infections in mice].
AB  - The MycoDot is a new diagnostic kit for tuberculosis which was devised by DynaGen
      Inc., USA. The MycoDot test is based on the detection of anti-mycobacterial
      antibodies in the serum samples of patients by employing plastic combs coated
      with lipoarabinomannan (LAM) antigen which is a highly immunogenic
      lipopolysaccharide presenting in the cell wall of all species of mycobacteria. It
      has been reported that healthy infected and BCG-vaccinated individuals do not
      react to the MycoDot test, while a positive reaction occurs in patients with
      active tuberculosis or atypical mycobacteriosis with good sensitivity and
      specificity. In this study, we evaluated the efficacy of MycoDot test for the
      detection of anti-LAM antibodies in sera of mice infected with Mycobacterium
      tuberculosis or M. avium complex (MAC). By using the MycoDot test, anti-LAM
      antibodies were positive in 2 out of 4 mice infected with M. tuberculosis 2 weeks
      before, while all of M. intracellulare-infected mice were negative at the same
      phase of infection. On the other hand, anti-mycobacterial (MB) antibodies were
      detected in the serum samples of mice infected with M. intracellulare as well as
      M. tuberculosis by home-made ELISA testing using whole cells of test mycobacteria
      as antigen. In the next experiment, mice were infected with M. avium. All the
      serum samples of mice obtained at 13 weeks after infection were negative for anti
      LAM antibodies in MycoDot test, whereas they reacted positively to anti-MB
      antibodies in ELISA test. These results indicate that the MycoDot test is capable
      of detecting M. tuberculosis infection but not MAC infection induced in mice.

PMID- 9545697
TI  - [Therapeutic efficacy of benzoxazinorifamycin KRM-1648 against experimental
      murine tuberculosis: (1). A study on the efficacy of short course treatment with
      the intratracheal and intravenous infection model].
AB  - OBJECTIVES: This study aims to compare in vivo activity of benzoxazinorifamycin
      KRM-1648 (KRM) with those rifampicin (RFP) and rifabutin (RBT) against
      experimental murine tuberculosis. STUDY DESIGN: Mice were infected with
      Mycobacterium tuberculosis or M. bovis by the intratracheal (i.t.) or intravenous
      (i.v.) routes, and treated for 10 days with various doses of each drug starting
      from the 9th or 11th day after the TB-infection. RESULTS: (A) A rapid test for in
      vivo evaluation of three rifamycins was conducted by examining the survival days
      of treated mice infected with 106 cfu of M. bovis Ravenel. Mice treated with KRM
      exhibited 2.13.7 times longer survival times, in comparison with those treated
      with RFP or RBT. (B) In the i.t.-model of M. bovis Ravenel infection, three
      rifamycin derivatives gave "distinctive dose-response curves" in the correlation
      of dose sizes with the mean survival times or "log10CFU/lungs reductions". (C) In
      M. tuberculosis Kurono infection models, the ranking of the anti-TB activity of
      the three rifamycins in each organ was as follows: i.t.-and i.v.-lungs: KRM >>
      RFP not equal to RBT, i.v.-spleen: KRM not equal to RBT > RFP, i.v.-liver: KRM
      not equal to RBT > RFP. (D) Based on the results of "log10CFU reduction" in
      different organs in M. tuberculosis Kurono infection models, "characteristic in
      vivo activity patterns of each rifamycin" were obtained. (E) The therapeutic
      efficacy of KRM in lungs was greater than in spleen and liver with any dose. In
      contrast, RBT exhibited more remarkable in vivo activity in the spleen and liver
      than in lungs. CONCLUSION: The prominent in vivo activity of KRM may allow small
      dose for effective therapy; 1/3 dose or less in comparison with those of RFP or
      RBT, or intermittent therapy of tuberculosis.

PMID- 9545698
TI  - [Biochemical and immunological properties of the fractions of tubercle bacilli].
AB  - In 1954, Dr. Yuichi Yamamura and his coassociates, National Sanatorium Toneyama
      Hospital, has reported the formation of experimental tuberculous cavity in
      rabbits. This work was a milestone of the researches in the field of cellular
      immunology. In 1960, I have started my scientific carrier in Kyushu University
      Medical School as the post-graduate student under the guidance of Prof. Yamamura.
      Since then, I have worked on the field of biochemical and immunological
      properties of tubercle bacilli. The arabinose mycolate, polysaccharides, cell
      wall skeleton (CWS) and trehalose dimycolate (TDM) were purified from tubercle
      bacilli and their Chemical structures and biological activities were investigated
      in detail in our laboratory. In 1971, we have reported that adjuvant active
      principle of tubercle bacilli was a CWS fraction, and the details of chemical
      structure and adjuvantity of mycobacterial CWS were investigated in our research
      group. The application of BCG-CWS to cancer immunotherapy was also studied. In
      1974, Prof. E. Lederer and his coworkers, University of Paris, have reported that
      N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP) was the minimum adjuvant-active
      structure of bacterial cell wall. We have synthesized several hundreds of MDP
      derivatives and selected, MDP-Lys(L18), romurtide, as the candidate of cytokine
      inducer for the clinical application. Romurtide is applied in cancer patients for
      the recovery of the number and functions of monocytes, neutrophils and platelets.
      These results suggest that the tubercle bacilli, especially, CWS and related
      synthetic MDP derivatives, are effective for the potentiation of host resistance
      against infectious diseases and cancer.

PMID- 9545699
TI  - [Nontuberculous mycobacteriosis; the present status and in the future. Mechanisms
      of host resistance to Mycobacterium avium complex and Mycobacterium tuberculosis
      infection].
AB  - In order to know profiles of the antimicrobial action of some microbicidal
      effector molecules against Mycobacterium avium complex (MAC) and M. tuberculosis
      (MTB), profiles of collaborating effects among reactive nitrogen intermediates
      (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) were
      studied, RNI and FFA exerted synergistic effects in killing MAC and MTB, while
      the combination of ROI (H2O2-mediated halogenation system) with FFA conversely
      caused antagonism. The combination of RNI with ROI displayed additive effects in
      killing MTB, whereas the same combination showed antagonistic effects against
      MAC. Murine peritoneal macrophages (M phi s) produced and/or released these three
      antimicrobial effectors in the order ROI, FFA, and RNI in response to cellular
      stimulation induced by their contact with MAC or MTB organisms. These findings
      indicate that the collaborating effect of RNI with FFA is crucial for M phi
      mediated intracellular killing of MAC and MTB. Secondly, we examined the modes of
      bacterial growth of MAC and MTB in murine peritoneal M phi s and A-549 type II
      alveolar epithelial cell line. The growth rate of these organisms was much larger
      in A-549 cells than in M phi s. In addition, the growth rate of high-virulence
      MAC (N-260 strain) was significantly larger than that of low-virulence MAC (N-444
      strain), when they were residing in M phi or A-549 cells. Although a high
      virulence MTB (strain Kurono) also showed much more rapid growth in M phi s than
      did low-virulence MTB (strain H37Ra), such a phenomenon was not observed for
      their intracellular growth in A-549 cells. MTB exhibited strong cytotoxic effects
      against M phi s but not against A-549 cells when resided in these cells. On the
      other hand, MAC organisms did not cause cytotoxicity even in M phi s. Although
      MAC and MTB infections caused significant increase in RNI production by M phi s
      but not by A-549 cells, there was no significant relationship between the degree
      of M phi RNI production by a given mycobacterial organism and its virulence.
      These findings indicate some important roles of type II alveolar epithelial cells
      as a target cell for primary invasion and transient growth of mycobacterial
      organisms in the host lungs.

PMID- 9545701
TI  - [Nontuberculous mycobacteriosis; the present status and in the future. 3-(2) Long
      term prognosis of Mycobacterium avium complex disease].
AB  - This paper shows long-term course of 71 patients with Mycobacterium avium complex
      (MAC) disease treated in National Hiroshima Hospital between 1977 and 1991 and
      were observed for more than 5 years or died between 6 months and years from the
      onset. In the patients who were not treated with chemotherapeutic agent or
      treated with less than 3 drugs, about 60 per cent deteriorated and few obtained
      persistent negativity of bacteria. In patients treated with at least 3 drugs out
      of isoniazid, rifampicin, ethambutol, ethionamide, cycloserine, clarithromycin
      and new-quinolones for more than 12 months, 59.2 per cent deteriorated, while
      29.6 per cent obtained negative conversion of bacteria by initial chemotherapy.
      However only 18.5 per cent remained negative during long term observation. In
      patients treated with at least 3 drugs including one aminoglycoside such as
      streptomycin for more than 12 months, 64.7 per cent obtained negative conversion
      and 35.5 per cent remained negative bacteriologically, while 23.5 per cent
      deteriorated. In twelve patients who were operated, only one patient
      deteriorated. The long-term prognosis of MAC disease under the chemotherapy
      mainly by antituberculous agents up to this time was still poor compared to that
      by short-term observation. Anticipated new regimens for MAC should be multidrug,
      to prevent secondary drug resistance.

PMID- 9545700
TI  - [Nontuberculous mycobacteriosis; the present status and in the future. 3--(1).
      The view of development of new drugs against nontuberculous mycobacterial
      infections].
AB  - It is obvious that the number of patients with pulmonary nontuberculous
      mycobacterial infections is increasing gradually in Japan. Of these infections,
      M. avium complex (MAC) is the most common cause, and is known to be resistant to
      many antimicrobial drugs. At present, no standard regimen which is able to
      control MAC infections completely is established. For these reasons, the
      development of new drugs with strong antimycobacterial activity which are not
      cross-resistant to conventional antimycobacterial drugs is urgently desired.
      Thus, we studied in vitro activities of various drugs which are expected to be a
      new promising drug against nontuberculous mycobacterial infections, and reviewed
      clinical impact of these drugs. 1) New quinolones New quinolones including
      ofloxacin, ciprofloxacin, levofloxacin and sparfloxacin (SPFX), are considered to
      be active against M. tuberculosis, M. kansasii, M. fortuitum, but are inactive
      against MAC, M. chelonae, M. abscessus, M. scrofulaceum. Both AM-1155 and Du
      6859a, newer quinolones, seemed to be comparable to or more active than SPFX
      which is considered to be most active now. 2) New macrolides Clarithromycin (CAM)
      has in vitro activities against various nontuberculous mycobacteria including
      MAC, and also has proven to have clinical potential not only for disseminated MAC
      infections in AIDS but also for pulmonary MAC infections. Therefore, CAM seems to
      be a candidate for one of the key drugs in the treatment of MAC infections.
      3)Rifamycins Rifabutin (RBT) and rifapentine exhibited more potent in vitro and
      in vivo antimycobacterial activities than rifampicin. RBT has already
      demonstrated clinical effect against intractable tuberculosis and MAC infections.
      Thus, RBT is recommended for the prophylaxis of M. tuberculosis and MAC
      infections in AIDS patients in US. KRM-1648 displayed much more potent in vitro
      and in vivo activities than rifampicin against both M. tuberculosis and MAC. It
      is needed an effort to confirm its therapeutic efficacies. Now clinical phase
      study is going on in US. 4) Phenazines Clofazimine (CFZ), an effective
      antileprosy drug, is known to be active in vitro against various mycobacteria
      including MAC, and often used as a component of combination chemotherapy for
      disseminated MAC infections in AIDS patients in US. Recently, CFZ new analogs
      have been developed, and it is necessary to evaluate its activities against
      nontuberculous mycobacteria.

PMID- 9545702
TI  - [Nontuberculous mycobacteriosis; the present status and in the future. Infection
      with human immunodeficiency virus (HIV) and nontuberculous mycobacteriosis].
AB  - Disseminated Mycobacterium avium-intracellulare complex (DMAC) infection is a
      common complication of AIDS. The cumulative incidence is 40% in patient surviving
      2 years after diagnosis of AIDS. AIDS patients with DMAC reduced life expectancy
      compared with those without. Antimycobacterial therapy with Clarithromycin (CAM)
      can significantly reduce bacteremia and improve symptoms, quality of life, and
      survival of patients with DMAC. Prophylactic therapy with Rifabutin, CAM and
      Azithromycin is effective and Synergic effect can be expected as Rifabutin and
      Azithromycin are administered together. But it is serious problem to get
      resistance to CAM when prophylactic therapy with CAM failed because we lose one
      of the most effective medicines against DMAC. It is recommended to start
      prophylactic therapy when CD4 Lymphocyte count falls below 50-75/microliters in
      patients who had opportunistic infection. In Japan, 32 cases of AIDS with NTM are
      reported. All of them are male and mean count of CD4+lymphocyte was
      11/microliters. Twenty three out of 32 were MAC and 6 were M. kansasii. Cases of
      NTM bacteremia were 9 (69.2%) and cases of those without bacteremia were 4
      (30.8%). Three out of 4 were cases of M. kansasii.

PMID- 9545703
TI  - [Short-term triple therapy with pantoprazole, amoxicillin and metronidazole in
      Helicobacter pylori infection].
AB  - BACKGROUND: The present study was conducted to investigate the efficacy and
      tolerability of a 7-day treatment with pantoprazole, amoxicillin and
      metronidazole for the eradication of Helicobacter pylori (H. pylori) infection.
      PATIENTS AND METHODS: Fifty patients (26 male, 24 female, age 18 to 86, mean 54
      years) with an active duodenal (n = 25) or gastric ulcer (n = 25) were recruited
      into the study, 48 patients being H. pylori positive at the study start. Patients
      were treated with pantoprazole (40 mg bid), amoxicillin (1 g bid) and
      metronidazole (500 mg bid) for 7 days and for another 21 days with pantoprazole
      (40 mg/od). Four weeks after the end of study medications the patients were re
      examined endoscopically and their H. pylori status was re-assessed using urease
      test, histology and 13C-urea-breath test. RESULTS: In 39 of 48 intention to treat
      patients, H. pylori infection was cured, according to 81% (95%-CI = 67 to 91%).
      In the per protocol population in 35 of 41 patients H. pylori was eradicated,
      which results in an eradication rate of 85% (95%-CI = 71 to 94%). Ulcer healing
      was endoscopically confirmed in 45 of 48 patients (94%; 95%-CI = 83 to 99%) after
      8 weeks. Six of 50 patients (12%) reported mild to moderate probable side-effects
      of the study medication. Cure of the infection was associated with a distinct
      reduction of the gastritis grade and activity. CONCLUSION: A 7-day triple therapy
      using pantoprazole, amoxicillin and metronidazole is an effective and cost
      effective alternative to regimens including clarithromycin for the treatment of
      H. pylori infection.

PMID- 9545704
TI  - [1997 gastroenterology update--I].

PMID- 9545705
TI  - [Space-occupying lesion of the liver hilus].

PMID- 9545706
TI  - [Pathogenesis and therapy of Hodgkin lymphoma].
AB  - Although the pathogenesis of Hodgkin's disease is not clear, molecular analyses
      reveal characteristic features. EBV infection can be demonstrated in more than
      50% of cases at the DNA or protein level. Recently, immunoglobulin gene
      rearrangements were found in single Hodgkin and Reed-Sternberg cells. Sequence
      analyses revealed that the rearranged Ig genes have frequently somatic mutations,
      which indicate that the cells are derived from the germinal center. These
      rearrangements may be used as defined markers to detect residual disease after
      chemotherapy. Modern polychemotherapy regimen and radiotherapy are very
      effective, and 60-90% of patients, depending on stage of the disease and risk
      factors, can be cured. Salvage therapy for relapsed patients including high-dose
      chemotherapy with autologous stem cell support frequently results in remission
      although duration is frequently short. New immunotherapy strategies with
      immunotoxins or bispecific antibodies are currently analysed in clinical studies.

PMID- 9545707
TI  - [Outcome of intensive care].
AB  - BACKGROUND: The mean hospital mortality of patients after intensive therapy in
      Germany is about 15%, the mortality within the intensive care unit about 8%.
      Short-term prognosis is mainly determined by severity of disease, type of disease
      and patient age. FACTORS IN INTENSIVE CARE: The impact of disease severity is
      measured by acute physiology score systems. The significance of disease
      categories becomes apparent in disease states with a continuing high mortality.
      Age is an independent risk factor. The higher risk of older patients cannot be
      explained by different diagnosis, and it is not secondary to a less aggressive
      therapy. The same factors mainly determine long-term prognosis. The 5-year
      survival rate after intensive therapy is around 60%, a 3-fold increase as
      compared to the general population. Dependent upon the disease category, survival
      curves of intensive care patients parallel survival curves of the general
      population 2 years after admission. Analysis of quality of life is based upon
      objective measurement and subjective estimation of health-related life quality in
      the physical, psychological, and social life domain. Patients after intensive
      therapy experience a moderate but significant decrease in quality of life. This
      is the case in global estimations of quality of life as well as in investigations
      of different life domains. CONCLUSION: The remaining quality of life is
      tolerable. This is in accordance with the positive overall judgement of intensive
      care by patients themselves. The chief problem of intensive care remain diseases
      with continuing high mortality.

PMID- 9545708
TI  - [Illnesses caused by amalgam?].
AB  - BACKGROUND: As side effects of dental amalgam have been mentioned allergy, oral
      lichen, electro-galvanism, amalgam tattoos of gingiva or oral mucosa, and
      undesirable esthetics. Patients with amalgam restorations show increased mercury
      levels in different body fluids compared to amalgam-free controls. An
      intoxication due to dental amalgam fillings, however, is not to be expected
      despite equivocal statements in the literature. SCIENTIFIC RESULTS: In contrast,
      recent studies revealed that dental amalgam contributes to mercury exposure less
      than assumed few years ago. Therefore, amalgam will stay an option as a
      restorative material in future. The removal of intact amalgam fillings in the
      intention of "detoxification" is not science-based. CONCLUSION: Successful caries
      prevention (e.g. due to the widespread use of fluoride) and the further
      development of esthetic restorative materials based on composite resins will
      limit the utilisation of amalgam. Thus, alternative materials have not been shown
      to have a lower rate of side effects (e.g. allergy) compared to amalgam.

PMID- 9545710
TI  - [Supraventricular tachycardia, II: Atrioventricular nodal reentry tachycardia:
      diagnosis and therapy].

PMID- 9545709
TI  - [Pseudoaneurysm with associated arteriovenous fistula after transfemoral
      puncture].
AB  - BACKGROUND: Local vascular complications after transfemoral cardiac
      catheterization occur with an incidence of 5%. Most commonly these lesions are
      pseudoaneurysms, av-fistulas, arterial dissections or direct vascular injuries.
      Undiagnosed vascular lesions can lead to fatal consequences especially in
      patients with chronic heart failure by av-fistula with significant shunt volume.
      CASE REPORT: We report a vascular complication of combined pseudoaneurysm and av
      fistula originated from the pseudoaneurysm. The lesion was diagnosed by color
      Doppler ultrasound. CONCLUSION: The suspicion of a vascular lesion after vascular
      catheterization should immediately lead to color Doppler ultrasound. Noninvasive
      duplexsonography will lead to early diagnosis of vascular complications and
      prompt further surgical or conservative intervention with reduction of long-term
      sequela and morbidity.

PMID- 9545711
TI  - [Poison and nocebo--2 aspects of toxicology].
AB  - BACKGROUND: Erroneously it is assumed that drugs promote health exclusively by
      interacting with the organism through chemical or physical forces. However,
      placebo phenomena are omnipresent in patients who believe in the value of a
      treatment, be it medical or paramedical. Conversely, nocebo phenomena originate
      from fear of detrimental effects attributed to a putative poison. Thus, both
      drugs and poisons release two different messages, the one being physicochemical,
      the other psychosocial. The latter is fostered by the public opinion, and man is
      a sensitive receiver. TYPICAL NOCEBO PHENOMENA: Here some epidemiological
      examples of nocebo phenomena will be presented. Each society selects the matching
      nocebos, today mainly as chemical exposures from oecological sources such as
      environment, buildings, emissions and industrial products. THERAPEUTICAL
      APPROACH: Suspicion of nocebo should not hamper the search for chemical poisons.
      Anxiety and fear furnish the neurobiological and evolutionary basis of the nocebo
      phenomena. Hence behavioural and conversational therapy, supported by
      antidepressants if needed, should be tried. Unfortunately, most patients expect
      their psychosocial problems instead to be declared as chemical.

PMID- 9545712
TI  - [Structure and activities of drug committees in Germany. Results of a survey of
      143 hospitals. Pharmaco-economic Study Group and Rational Drug Therapy of the
      German Society of Clinical Pharmacology and Therapy].
AB  - BACKGROUND: To obtain information on the structure, present activities and
      decision making process of hospital drug committees in Germany in 1995 a
      questionnaire with 36 items was designed and sent to 450 hospitals in Germany
      with more than 400 beds. 143 returned questionnaires could be evaluated. RESULTS:
      According to hospital size the median value of the annual drug budget 1993 ranged
      between DM 2.4 Mio for hospitals with less than 500 beds and DM 30.0 Mio for
      university hospitals with more than 1,000 beds (including blood and blood derived
      products). In 53% of drug committees a pharmacist held the position of the
      chairman, followed by medical specialists (32%), (clinical) pharmacologists held
      this position only in 8% of the hospitals, but in almost 50% of the university
      hospitals. In most cases all clinical specialties are represented in the drug
      committee, the number of members ranging between 5 and 40 (median 12). The number
      of drugs included in the internal drug list ranging between 400 in hospitals with
      < 500 beds and about 700 in university hospitals was strongly correlated with the
      number of beds and, interestingly, with the number of drug committee members.
      Treatment guidelines were implemented mainly for antiinfectives (87%), infusion
      solutions (30%), antiemetic drugs (5-HT3-receptor antagonists, 27%) and blood and
      blood-derived products such as intravenous immunoglobulins (23%). However,
      effective control of these guidelines was only performed in about 50% of the
      hospitals. A drug information service was provided in most hospitals, where 95%
      of queries were answered by pharmacists. CONCLUSION: The results of our survey
      showed, that German hospital drug committees vary considerably with regard to
      their function and control mechanisms on drug use. Most of the responders would
      appreciate a more intensive exchange of current problems and treatment
      guidelines.

PMID- 9545713
TI  - [Eczema of the nipple: cancer or not?].
AB  - Paget disease of the nipple is a rare unique presentation of breast cancer. The
      main differential diagnosis is dermatitis. We describe two patients with mammary
      Paget: one, a women aged 41, with limited ductal carcinoma in situ and the other,
      a women of 56 years, with invasive carcinoma. A third patient, a woman of 46
      years, had typical eczema of the areola. This disease usually leads to less well
      circumscribed lesions than Paget. The treatment of Paget disease is not
      essentially different from that of any other mammary carcinoma. Eczema of the
      areola is treated with corticosteroids, to which the disease should respond
      favourably within three weeks.

PMID- 9545714
TI  - [The value of roentgen pictures in rheumatoid arthritis].
AB  - Rheumatoid arthritis leads to many abnormalities in radiographs as a result of
      irreversible destruction of cartilage or underlying bone. Radiographs of hands
      and feet provide the most useful information. Erosions and joint space narrowing
      in particular can be assessed reliably, and give a good impression of the
      destruction of the joints. Several validated scoring methods are available to
      assess the severity and progression of joint damage. Abnormalities are already
      present shortly after onset of the disease. About 70% of the patients develop
      erosive disease and in the majority of the cases erosions are present one year
      after onset. Patients who are rheumatoid factor positive in particular develop
      erosions. Damage occurs earlier and is often more severe in the joints of the
      feet than in joints of the hands. The early occurrence of irreversible joint
      destruction and the availability of treatment effective in reducing this damage
      necessitates early treatment of patients with RA.

PMID- 9545715
TI  - [Complications, hospital mortality and survival following partial
      pancreaticoduodenectomy].
AB  - OBJECTIVE: To analyse hospital mortality, complications and survival of patients
      after subtotal pancreaticoduodenectomy in the Academic Medical Centre, Amsterdam,
      the Netherlands, 1983-1996. DESIGN: Partly retrospective (1983-August 1987),
      partly prospective (September 1987-1996). METHOD: Patient characteristics,
      indication for surgery, postoperative complications, mortality and survival of
      patients who underwent subtotal pancreaticoduodenectomy were recorded in a
      computer database. Patients were subdivided into three groups (1983-September
      1992; October 1992-1994; 1995-September 1996) to analyse the influence of change
      in surgical technique and the increase of experience. RESULTS: From 1983-to
      September 1996, 312 consecutive patients underwent a subtotal
      pancreaticoduodenectomy. Hospital mortality decreased from 4.9% to 1.4% in the
      last period (1995-1996). The complication rate decreased from 60% to 41%. The
      hospital stay decreased from median 24 days to 16 days. The actualized 5-year
      survival analysed for patients operated from 1983-to September 1992 was 31%.
      Patients with ampullary tumours had a 5-year survival of 50%. The 5-year survival
      of patients with bile duct and pancreatic carcinoma was 24% and 15% respectively.
      CONCLUSIONS: Subtotal pancreaticoduodenectomy can be performed safely with a low
      mortality (< 2%) in specialised centres. The morbidity is still substantial
      (40%). The survival is mainly dependent on type of tumour and patient selection
      and is approximately 50% for patients with ampullary tumours. The pylorus
      preserving procedure has become the standard operation.

PMID- 9545716
TI  - [Hospital experience and hospital mortality following partial
      pancreaticoduodenectomy in The Netherlands].
AB  - OBJECTIVE: To analyse the effect of hospital experience on mortality after
      subtotal pancreaticoduodenectomy in the Netherlands. DESIGN: Retrospective
      evaluation. METHOD: Information on hospital mortality and pancreatic resection in
      1994 and 1995 in the Netherlands was obtained from the National Medical Register.
      Subanalysis was carried out of surgical mortality by age and hospital experience.
      RESULTS: Approximately 50% of the pancreaticoduodenectomies in the Netherlands
      were performed in hospitals with limited experience (< 5 procedures per year).
      Hospital mortality was higher in small-volume hospitals than in hospitals with
      experience (> 25 procedures per year): in 1994 17.2 and 0% and in 1995 14.6 and
      2.9%, respectively (p < 0.05). Mortality was higher in patients older than 70
      years compared with patients younger than 55 (p < 0.05). CONCLUSION: There was a
      correlation between mortality after pancreaticoduodenectomy and hospital
      experience. Therefore these procedures should be performed in centres with
      experience.

PMID- 9545717
TI  - [Ascites due to hypothyroidism].
AB  - A 77-year-old man presented with ascites which was due to hypothyroidism. After
      the ascites had been brought into remission by salt restriction, diuretics and
      paracentesis, monotherapy with levothyroxine prevented recurrence. Ascites
      reappeared as soon as levothyroxine was withdrawn due to the patient's non
      compliance. Distinctive aspects of this type of ascites are the high
      concentration of total protein in the ascites and the high serum-to-ascites
      albumin gradient (SAAG). The pathogenesis of ascites in hypothyroidism is
      unknown. Possible hypotheses include increased capillary permeability,
      obstruction to lymphatic flow caused by hyaluronic acid-albumin complexes, and
      diminished water diuresis due to excess antidiuretic hormone. A patient with
      unexplained ascites should be tested for hypothyroidism, especially when the SAAG
      is high (> 11 g/l).

PMID- 9545718
TI  - [Influenza in the 1996/'97 season; vaccine composition for the 1997/'98 season].
AB  - The first indication of flu activity in the Netherlands in the 1996/'97 season
      was the isolation of an A/H3N2 influenza virus in week 48 of 1996. In subsequent
      weeks influenza viruses were isolated sporadically. The clinical influenza
      activity increased from week I of 1997 and reached its peak in week 4 of 1997.
      Simultaneously with the increase of clinical influenza activity, an increasing
      number of influenza viruses were isolated. The epidemic had a relatively small
      extent. Initially, A/H3N2 influenza viruses were predominant, but in the second
      half of the epidemic an increasing number of influenza B viruses were isolated as
      well. The A/H3N2 viruses were antigenically fairly strongly distinct from the
      variants prevalent in the preceding years. This season influenza A/HINI viruses
      did not play a significant role and only one virus of this subtype was isolated.
      All influenza A/H3N2, A/HINI and B viruses isolated were antigenically similar to
      the vaccine strains.

PMID- 9545719
TI  - [Statement of ingredients of cosmetics].
AB  - Since January 1st 1997 there is European legislation labelling that cosmetic
      products are supplied with a list of their ingredients. The ingredients are given
      in order of decreasing concentration using the nomenclature 'International
      nomenclature cosmetic ingredient' (INCI). This enables dermatologists to identify
      the allergenic components of cosmetic products in patients with allergic contact
      dermatitis caused by cosmetics, and enables allergic patients to purchase other
      cosmetic products without risking a recurrence of dermatitis.

PMID- 9545720
TI  - [Syncopes with simultaneous use of terfenadine and itraconazole].

PMID- 9545721
TI  - [Syncopes with simultaneous use of terfenadine and itraconazole. Drug Monitoring
      Board].

PMID- 9545722
TI  - [Diagnostic and therapeutic dilemmas in malignancy during pregnancy].
AB  - In four pregnant women, aged 28, 29, 30, and 35, malignancies were diagnosed:
      synoviosarcoma, gastric carcinoma, non-Hodgkin B cell lymphoma and
      undifferentiated adenocarcinoma in one of the labia vulvae, respectively. The
      first three women eventually died, the first before giving birth, the last woman
      was treated surgically and was alive without recurrence two years after
      treatment. Pregnancy can lead to diagnostic dilemma and delay as many symptoms of
      a malignancy are not recognised as such but are attributed to the pregnant state
      and because of reluctance to apply diagnostic tools which can be harmful to the
      foetus. It can also lead to therapeutic dilemma and delay because several
      therapies may also harm the foetus.

PMID- 9545723
TI  - [Malaria therapy; ups and downs, how much longer?].
AB  - The natural products quinine and artemisinine have been effective antimalarials
      for centuries. Most synthetic antimalarials were developed because of pressure of
      war; against all some degree of resistance has developed. The newer drugs are too
      expensive for large-scale use. Development of new antimalarials is financially
      too risky for the pharmaceutical industry. Co-operation among industries,
      research institutes, governments and international organizations is coming off
      the ground. Dutch researchers should contribute to international malaria research
      for humanitarian reasons and out of self-interest, for the benefit of public
      health.

PMID- 9545724
TI  - [Immunology in medical practice. I. Introduction].
AB  - Fundamental immunology has seen a tremendous development in the past decades.
      This has resulted in a large body of knowledge, part of which has led to
      applications in laboratory diagnosis, but of which little has made its way to the
      clinic in terms of new therapies. The progress in understanding pathogenesis of
      diseases is also slow. This journal is planning a series of articles that
      highlight the recent achievements of immunology and their consequences for
      understanding and treating disease.

PMID- 9545725
TI  - [Immunology in medical practice. II. Antiphospholipid antibodies in pregnancy].
AB  - Antibodies against phospholipids are a risk factor for thrombotic disorders, but
      also for foetal death, pre-eclampsia, foetal distress and dysmaturity. This group
      of antibodies (aPLab) includes lupus anticoagulant (LAC) and anticardiolipin
      antibodies (aCL). These antibodies are encountered in patients with systemic
      lupus erythematosus (SLE), but also in patients with lupus-like disease and in
      women with (a history of) symptoms compatible with the antiphospholipid syndrome.
      Screening for a aPLab is advisable in these patients when they want to conceive
      and in women with recurrent foetal death after the 12th week of pregnancy. It is
      not clear if the antibodies exert a direct noxious action or are an accompanying
      phenomenon. Secondary prevention is possible with acetylsalicylic acid (80
      mg/day), if desired in combination with subcutaneous heparin (5000-12,000 units
      twice daily). The thrombosis prophylaxis should be continued for 6 weeks after
      delivery.

PMID- 9545726
TI  - [The treatment of malaria].
AB  - The diagnosis of malaria should include the species involved and in case of P.
      falciparum infection the parasitaemia index: the percentage of the infected red
      cells. P. vivax, ovale and malariae infection are treated with chloroquine, in
      case of P. vivax and ovale malaria followed by primaquine. Mefloquine and
      halofantrine are indicated for chloroquine-resistant vivax infections. Advice on
      management and treatment is different for mild and severe (> or = 5% infected
      erythrocytes or presence of complications) P. falciparum infections. Mild
      infections may be treated on an outpatient basis. In severe infections quinine
      has to be started immediately, while frequent checks of vital functions and blood
      parameters are indicated. New treatment options are the use of artemisinine
      (preparations) or atovaquone, both efficacious and low in adverse effects and
      toxicity.

PMID- 9545727
TI  - [Consensus prevention of crib death. CBO (Central Guidance Organization for Peer
      Review)].
AB  - The sudden and unforeseen death of a child in the first two years, usually
      happening during a sleeping period, is known as cot death. As cot death is a very
      tragic and dramatic experience for the family, it is important to reduce its
      incidence. In the period between 1972 and 1987, the number of cot deaths
      initially increased, but during the last decade a substantial reduction could be
      observed. This fluctuation can be connected with the position in which the baby
      is put to sleep. From 1970 the prone sleeping position was strongly recommended.
      Since then, the number of cot death cases increased. From 1987, a causal
      relationship between the prone sleeping position and cot death was suspected. As
      a result the prone sleeping position was strongly advised against. A reduction of
      cot death cases was then observed. By now, the role of many other factors in cot
      death has been perceived. The risk of cot death is increased if these factors act
      at the same time. Some of these factors that promote cot death come from the
      child's environment and can be influenced when kept in mind. Apart from the prone
      or side sleeping position, heat congestion, unsafe bed material and smoking in
      the presence of the child substantially increase the risk of cot death. The main
      recommendations of the committee which drew up the Dutch consensus report on
      prevention of cot death are therefore aimed at avoiding the above mentioned risk
      factors. Continuation of research is necessary to further reduce the current
      number of some 50 cases of cot death which happen yearly in the Netherlands.

PMID- 9545729
TI  - [Chronic fatigue syndrome].

PMID- 9545731
TI  - [Suppurative hidradenitis].

PMID- 9545730
TI  - [Chronic fatigue syndrome].

PMID- 9545728
TI  - [Recurrent Plasmodium vivax malaria in spite of primaquine follow-up treatment].
AB  - Two patients, a 25-year-old woman and a 62-year-old man, with Plasmodium vivax
      infection, suffered repeated attacks of malaria despite standard treatment with
      chloroquine and subsequently primaquine. The relapses were due to a combination
      of decreased primaquine sensitivity and incorrect prescription of primaquine.
      Primaquine is administered as diphosphate (salt), but the required amount has to
      be prescribed as base (26.3 mg diphosphate corresponds to 15 mg base).

PMID- 9545732
TI  - [Genetic counseling: should side issues become main issues?].
AB  - Three people applied for genetic counselling, but during the consultations the
      clinical geneticist discovered other problems for which advice could have been
      given but was not asked. This caused a serious dilemma. The first person was a
      woman who wanted to know the risks of epilepsy for her potential offspring, but
      then it became clear that she appeared to have Huntington's disease in the
      family. The second person was a man who wanted to know about the genetic risks
      for his offspring of a borderline psychiatric disorder, but the geneticist,
      seeing that the partner had severe limb defects, wondered whether these were
      caused by a genetic disorder. The third patient was a pregnant woman who came
      asking about the risks caused by mental retardation in one of her ancestors, but
      who appeared to be a heavy drinker and user of cocaine and ecstasy. In dealing
      with such 'secondary' problems, it should be kept in mind that persons seeking
      advice must decide for themselves whether or not they want to be informed
      regarding these problems or not.

PMID- 9545733
TI  - [Optimal world-wide obstetrical care; a WHO report].
AB  - 'Safe motherhood; care in normal birth: a practical guide' is a document produced
      by an international technical working group of the World Health Organization.
      This report addresses issues of care during normal birth irrespective of country
      or region. Routine interventions and non-interventions in the physiological
      processes of pregnancy and labour are analysed and assessed for their scientific
      validity. Scientific foundation of obstetric practice is considered an important
      step towards worldwide demystification of obstetric practice, which now often
      relies on authority, culture and habit. For risk assessment, the cornerstone of
      the Dutch system of obstetric care, an evidence-based strategy is imperative.
      This requires scientific training in schools of midwifery.

PMID- 9545734
TI  - [Endothelins: possibly a new pharmacological approach in cardiovascular diseases,
      kidney diseases and oncological disorders].
AB  - Only 10 years ago, the vasoconstricting peptide endothelin was discovered; it is
      produced by endothelial cells. Different isoforms and receptors of endothelin
      have been identified. The effects of endothelin-I, the most important isoform,
      are mainly vasoconstriction and proliferation of cells. In the last few years
      endothelin receptor antagonists have become available, which can delineate the
      clinical importance of the endothelin system. Possible indications for endothelin
      receptor blockers are renal disease (acute and chronic renal failure) and
      cardiovascular disease (heart failure; restenosis after percutaneous transluminal
      coronary angioplasty (PTCA); pulmonary hypertension; systemic hypertension).
      There is also a possible role for endothelin receptor blockers in oncology
      (prostatic carcinoma). Currently clinical trials are being carried out to
      determine the efficacy of these compounds for the above-mentioned indications.

PMID- 9545735
TI  - [Pleurodesis in malignant pleural effusion].
AB  - About 50% of the pleural effusions diagnosed are caused by a malignancy,
      especially by thoracic, pulmonary and ovarian cancer and lymphomas. The
      accumulation of fluid is caused by metastasization to the pleura and obstruction
      of lymph vessels and nodes. The effusion generally decreases if the tumour
      responds to systemic treatment. However, frequently this does not occur and the
      fluid has to be removed, to alleviate symptoms such as dyspnoea, coughing and a
      heavy sensation in the chest. Possible surgical therapies are draining through a
      needle or a drain, (partial) pleural resection and the creation of a pleuro
      peritoneal shunt. Disadvantages of these are early recurrences, the severity of
      the intervention and (or) the high morbidity and mortality. The current standard
      treatment is pleurodesis brought about by a sclerosing agent, usually via a
      drain. The substances preferably used for this purpose are, in the order of
      decreasing importance, tetracycline, bleomycin or talc, doxycycline or
      minocycline. The most frequent adverse effects are chest pain and fever during
      and after the pleurodesis.

PMID- 9545736
TI  - [Relationship between air pollution due to traffic, decreased lung function and
      airway symptoms in children].
AB  - OBJECTIVE: To assess whether air pollution by traffic was related to lung
      function and chronic respiratory symptoms in children living. DESIGN:
      Descriptive. SETTING: The province of South Holland, the Netherlands. METHODS: In
      the period May through July of 1995 pulmonary function tests and questionnaires
      were obtained from 1,092 and 1,068 children respectively in six city districts
      near busy motorways in the province of South Holland. In the same period, indoor
      measurements were performed at 12 schools of NO2, black smoke and PM10 dust
      density. Lung function data were analysed by multiple linear regression and
      respiratory symptoms were analysed by multiple logistic regression. As
      independent variables, distance between motorway and home, passenger car traffic
      density and lorry traffic density on the motorway, and black smoke and NO2
      concentrations in schools were taken. RESULTS: Significant differences in lung
      function and respiratory symptoms were found between children living in different
      city districts. Lung function as well as symptoms were associated with lorry
      traffic density on the motorway. The validity of these findings was supported by
      associations between black smoke concentrations (representative for diesel soot)
      and lung function as well as respiratory symptoms. In contrast, there was no
      association between passenger car traffic counts or NO2 and lung function or
      respiratory symptoms. CONCLUSION: The results suggest that air pollution by lorry
      traffic can lead to reduced lung function and to an increased prevalence of
      chronic respiratory symptoms in children living near major motorways.

PMID- 9545738
TI  - [Asystole due to complex partial epilepsy].
AB  - A 56-year-old man was seen in the Emergency Room because of sudden and transient
      loss of consciousness. An asystole was diagnosed with 10 S duration after which a
      pacemaker was implanted. The patient had experienced such collapses before,
      preceded by odd smell sensations. After the implantation of the pacemaker, the
      patient did not collapse again but still experienced attacks of the same smell
      sensations combined with a strange feeling in his stomach. An EEG, recorded
      during such an attack, showed epileptic activity predominantly over the right
      hemisphere while at the same moment a pacemaker rhythm was observed. After the
      epileptic activity had stopped, normal sinus rhythm reappeared. On anticonvulsant
      therapy the attacks disappeared completely.

PMID- 9545739
TI  - [Cancer incidence in the area of Schiphol in 1988-1993].

PMID- 9545740
TI  - [Puerperal fever: an old enemy in aggressive form].
AB  - Two previously healthy women, aged 30 and 35 years, suffered pain in the lower
      abdomen, one before and the other after spontaneous delivery at 40 and 33 4/7
      weeks of amenorrhoea, respectively, while a third woman, aged 33, at 36 weeks of
      amenorrhoea developed pain in the lower abdomen, fever, vomiting, and diarrhoea.
      All three women were found to have a uterine infection caused by streptococci of
      Lancefield group A (group A Streptococcus, GAS). In one woman, the diagnosis was
      made rapidly so that antibiotic treatment could be instituted in time; the other
      two developed sepsis and multiorgan failure, with a fatal issue in one of them.
      The three children also were septic, two recovered after treatment and one died.
      Since the eighties, serious GAS infection has been on the increase. The worst
      manifestation is the toxic shock syndrome caused by streptococci. Abdominal pains
      after delivery may be a first sign of this, and should not too readily be
      interpreted as just after pains. The condition may also develop before delivery.
      In view of the high mortality rate, early diagnosis and antibiotic treatment are
      of vital importance for mother and child.

PMID- 9545741
TI  - [Is the pulmonary artery catheter discredited because of ignorance?].
AB  - Recently in an observational study the use of a pulmonary artery catheter in
      critically ill patients was associated with an increase in both mortality and
      utilization of resources when compared with case-matched control patients. The
      authors corrected for selection bias by using a propensity score. The publication
      of this article elicited a flood of commentary in both medical journals and the
      lay press. Critical assessment of this study and other studies about pulmonary
      artery catheterization in our opinion supports the view that it is probably not
      the use of the catheter itself, but physicians' insufficient knowledge of right
      heart catheterization and the specific treatment resulting from its use that is
      at fault.

PMID- 9545742
TI  - [Immunology in medical practice. III. Disseminated lupus erythematosus: disturbed
      apoptosis?].
AB  - The main feature of systemic lupus erythematosus (SLE) is formation of
      antinuclear antibodies, particularly against double-stranded (ds) DNA. This
      autoimmune response is T cell- and (auto)antigen-dependent, but dsDNA is very
      poorly immunogenic. Recent data suggest that the nucleosome is the principal
      autoantigen in SLE. DNA is present in the circulation of SLE patients in the form
      of nucleosomes. In vivo, nucleosomes can only be generated through apoptosis.
      There is increasing evidence that apoptosis is disturbed in murine and human SLE.
      Nucleosomes have a high affinity for heparan sulphate in the glomerular basement
      membrane. By forming complexes with nucleosomes, antinuclear antibodies (both
      nucleosome-specific and anti-dsDNA autoantibodies) acquire a high affinity for
      the glomerular basement membrane, an initial key event in the development of
      lupus nephritis.

PMID- 9545743
TI  - [Drug treatment of prostatic carcinoma].
AB  - The basis for the medical treatment of prostate cancer is inhibition of the
      influence of testosterone on the prostate. Surgical castration is in 1997 still
      the gold standard; it reduces the testosterone level by 90% and the level of
      dihydrotestosterone (the active metabolite) by 60%. In the eighties luteinising
      hormone releasing hormone (LH-RH) analogues were introduced to avoid the
      psychological burden of castration. After an initial stimulation (the flare-up)
      testosterone decreases to castrate level within 3 weeks. Recently (non-steroidal)
      anti-androgens, competitive inhibitors of dihydrotestosterone on receptor level
      were introduced. There are also drugs which inhibit the conversion of
      testosterone to dihydrotestosterone: 5 alpha-reductase inhibitors. Non-steroidal
      anti-androgens and 5 alpha-reductase inhibitors do not decrease the testosterone
      level and therefore cause less loss of libido and energy than castration.
      Combination of (chemical) castration and anti-androgens is called maximum
      androgen blockade. This treatment has limited additional value in proportion to
      the increase in side effects and costs. A new form of treatment is intermittent
      androgen blockade. With this strategy growth of hormone-insensitive cells in the
      prostate, which is considered the main determinant of the poor prognosis, might
      be delayed with reduction of side effects and costs. The role of imidazoles is
      still investigated; the role of cytotoxic drugs is mainly palliative.

PMID- 9545745
TI  - [Alleviation of inoperable malignant colon stenosis using endoscopic placement of
      an endoprosthesis].
AB  - Treatment modalities for patients with an obstruction due to an irresectable
      malignant stenosis of the colon are: a palliative colostomy proximal of the
      obstruction, radiotherapy, laser therapy, cryosurgery, and photodynamic therapy.
      In 4 patients, 3 men and 1 woman of 70, 66, 74, and 38 years respectively with
      obstruction ileus caused by an irresectable distal colonic carcinoma, a self
      expanding wallstent was successfully placed endoscopically in the stenosis of the
      latter three as a palliative measure, resulting in the unimpeded passage of
      faeces and intestinal gas.

PMID- 9545746
TI  - [Abdominal wall metastasis following surgical removal of colorectal carcinomas].
AB  - Abdominal wall metastases after laparoscopic resection of colorectal cancer have
      been reported by various authors. It appeared that abdominal wall metastases
      occur more frequently after laparoscopic than after conventional, open resection
      of colorectal cancer. However, the frequency of abdominal wall metastases after
      laparoscopic surgery varies from only 0 to 1.9% in centres with sufficient
      relevant experience, whereas after conventional resections the frequency is 0.8
      3.3%. A randomized clinical study comparing laparoscopic with conventional
      resection of colon cancer is necessary to assess the optimal surgical approach to
      colon cancer. Such a trial has been set up.

PMID- 9545747
TI  - [The 'Colon cancer laparoscopic or open resection' (COLOR) trial].
AB  - The value of laparoscopic surgery for colorectal malignancy as compared with open
      surgery will be determined in the COLOR-trial. The disease-free survival time is
      the primary end point. Twenty-one hospitals in the Netherlands and Scandinavia
      will participate in the trial. In the COLOR trial 1500 patients with colon
      carcinoma will be randomised for either a laparoscopic or open colon resection.

PMID- 9545748
TI  - [Temperature measurement using the tympanic membrane infrared meter].

PMID- 9545749
TI  - [The 'medical work disability criterion'].

PMID- 9545750
TI  - [Hodgkin's disease].

PMID- 9545751
TI  - [Communication between treating physician and occupational physician in the
      monitoring of illness absenteeism].

PMID- 9545752
TI  - [Amebic abscess in the liver; early suspicion, late detection].

PMID- 9545754
TI  - Plasma concentrations of antipsychotic drugs in psychiatric inpatients.
AB  - In current psychiatric therapy, two or more kinds of antipsychotic drugs are
      usually prescribed in Japan. However, there are few data on the therapeutic
      plasma concentrations of antipsychotic drugs or on the correlation between the
      daily dose and the plasma concentration, in cases where several antipsychotic
      drugs had been prescribed for each patient. We measured the therapeutic plasma
      concentrations of 9 antipsychotic drugs in 24 psychiatric inpatients during a 6
      month period. They were treated with fixed dosages of antipsychotic drugs. Plasma
      samples were collected early in the morning once a month, and the concentrations
      of antipsychotic drugs were determined by gas chromatography with nitrogen
      phosphorus detection, high-performance liquid chromatography (HPLC) with
      fluorescence detection and HPLC with UV detection. The plasma levels of
      chlorpromazine, levomepromazine, thioridazine, haloperidol, bromperidol,
      zotepine, oxypertine, sulpiride and sultopride were 21.8-92.4, 31.7-156, 101-203,
      16.4-56.2, 2.72-11.7, 13.6-84.0, 29.9-80.4, 70.1-1,120 and 35.7-2,990 ng/ml,
      respectively. A linear correlation between the daily dose and the plasma
      concentration was noted for sultopride, levomepromazine, sulpiride, haloperidol,
      chlorpromazine and zotepine.

PMID- 9545753
TI  - Genetic polymorphisms detectable in human urine: their application to forensic
      individualization.
AB  - This review describes several types of genetic polymorphism, which have recently
      been identified in human urine in our laboratory, and have also been found in
      other human body fluids such as blood, saliva and semen. These include
      uropepsinogen, ribonuclease, deoxyribonuclease I (DNase I), deoxyribonuclease II
      (DNase II), 43-kDa glycoprotein, alpha-L-fucosidase, glutamate pyruvate
      transaminase, alpha-2-HS-glycoprotein, transferrin and vitamin D-binding protein.
      Several substances can be detected more easily in urine than in plasma. The
      concentrations of uropepsinogen, DNase I and DNase II in blood plasma are too low
      for analysis, whereas those in urine are high enough for easy typing. In
      practice, DNase I-polymorphism is one of the most useful genetic markers for
      practical purposes, because of its higher content in various body fluids
      including urine, a well-balanced gene frequency, and its easy and accurate
      detectability. Furthermore, several genetic markers previously identified in
      blood and/or other forensic samples can be phenotyped reproducibly and easily
      from the corresponding urine samples. Thus, urine, in addition to the convenience
      and non-invasive nature of its collection, is by no means inferior to blood as a
      sample source for typing in the field of forensic science. Biochemical and
      serological typing of genetic polymorphisms present in human urine could offer
      useful information to practising forensic biologists for forensic
      individualization of urine samples.

PMID- 9545755
TI  - [Analysis of sudden death caused by intestinal obstruction].
AB  - Five autopsy cases of sudden death caused by intestinal obstruction are reported.
      The causes of death of the cases were duodenal obstruction of impacted food
      stuff, ileocaecal obstruction caused by Crohn's disease, incarceration of
      inguinal hernia, intestinal obstruction caused by heterotopic pancreas and
      paralytic ileus. In three cases, the patient was in cardiopulmonary arrest on
      arrival at hospital, and in the remaining cases the patient died within 12 hours
      from the beginning of treatment; therefore, a correct clinical diagnosis was not
      made before the death in all cases. All the patients had from one to three days
      history of nausea and abdominal pain, major complications of intestinal
      obstruction. Among all cases, the duration from the onset to death was the
      shortest in the case of a patient complicated with schizophrenia. It is
      characteristic that the patients of all cases died suddenly and resuscitation was
      not successful. Regarding the laboratory data of a hospitalized patient, marked
      hemoconcentration and an increased level of BUN/Cr ratio and blood sugar were
      shown. The patient who died from duodenal obstruction caused by impacted food
      stuff had suffered from depression for six years, and the patient who died from
      paralytic ileus had suffered from schizophrenia for about 23 years. In both
      cases, it is characteristic that the complaints of the patient were poorer than
      what would be expected. Furthermore, these patients had been taking medication of
      psychotic, anti-depressant and anti-parkinsonism drugs; therefore the combination
      of these drugs was thought to be reflected in the bowel movement.

PMID- 9545756
TI  - Determination of sibship by microsatellite typing in a deficiency case of
      disputed maternity: further study.
AB  - In a deficiency case of maternity dispute where the father and his two wives were
      dead and only the six children were available for testing, we analyzed three sex
      linked short tandem repeat (STR) loci DYS19, HPRT, and AR. On the basis of the
      typing results of the HPRT and AR loci, we obtained probabilities of maternity
      ranging from 0.9256 to 0.9724 for five of the six children. The results supported
      those of typing for 24 conventional hemogenetic markers and 11 autosomal STRs,
      enabling us to establish maternity. The present study demonstrates the utility of
      sex-chromosomal STR typing in the solution of deficiency cases of disputed
      parentage.

PMID- 9545757
TI  - [A simple technique for the genotyping of TH01 locus].
AB  - It is difficult to differentiate between type 9.3 and 10 at the TH01 locus.
      Therefore, we designed three primers including allele-specific primer for the
      type 9.3. Our primer sets gave shorter fragments ranging from 62 to 81 bp than
      those in other reports, allowing each allelic band to be resolved by 10% non
      denaturing polyacrylamide gel electrophoresis and stained with SYBR Green I. TH01
      typing was successfully applied to human remains such as sera, whole bloods and
      blood stains made about 80 years ago without extracting DNA from them. The simple
      and fast methods for TH01 typing as demonstrated herein will be useful in the
      field of forensic practice.

PMID- 9545758
TI  - A case of disseminated intravascular coagulation probably arising from sudden
      infant death syndrome.
AB  - The cause of death in a 45-day-old male infant who was found apneic at home and
      died 21 hours later was disseminated intravascular coagulation (DIC). The patient
      was admitted to a hospital in a state of cardio-respiratory arrest. The initial
      diagnosis was interrupted sudden infant death syndrome. The patient remained
      apneic, and recurrent discharge of bloody stool was the dominant clinical
      findings. He died without spontaneous respiration being restored. The autopsy
      revealed hemorrhages in the lungs and the ventricular septum and the free wall of
      the left ventricle of the heart. Microscopically, fibrin thrombi were noted in
      the large intestine and heart. The DIC was probably triggered by a widespread
      endothelial injury caused by severe hypoxia and acidosis originating from the
      apnea and cardiac arrest lasting longer than 30 min.

PMID- 9545759
TI  - A sudden death case from retropharyngeal abscess.
AB  - A sudden death case, a 21-year-old man, from retropharyngeal abscess is reported.
      It seemed to be caused by an injury in the posterior wall of the pharynx by an
      ingested foreign body. Because he had never consulted a doctor, it had grown
      large in several days and ruptured into the pharynx, and he died suddenly from
      airway obstruction by the inhaled pus.

PMID- 9545760
TI  - [An autopsy case of carbon dioxide intoxication].
AB  - A 44-year-old male, engaged in the transportation of dry ice, was found dead on
      the floor of the freezer of his refrigerator car which was parked in front of the
      place where he was scheduled to make a delivery. Autopsy was performed to
      investigate the cause of death. Apart from the signs of acute death, no other
      significant findings were obtained, either macro or microscopically; carbon
      dioxide poisoning was thus strongly suspected. We created a simulation experiment
      by using the refrigerator car to reproduce the events of the accident. The oxygen
      concentration in the freezer was 21.0% as indicated by oxygen sensors, but
      decreased to 17.1-17.4% when the engine was stopped. This decrease in oxygen
      concentration supposedly results from the production of carbon dioxide by the
      vaporization of dry ice. Carbon dioxide concentration in the air could be
      calculated from the change in the oxygen concentration in the closed space of the
      freezer. The concentration was assessed at 17.1-18.6%. An oxygen concentration of
      17.1-17.4% does not of itself cause serious hypoxia, but a carbon dioxide
      concentration of 17.1-18.6% probably causes serious intoxication, because this
      value is beyond that of intoxication levels published in references. Therefore,
      we concluded that the cause of death in this case was carbon dioxide
      intoxication.

PMID- 9545761
TI  - [A case of dural sinus thrombosis during the medication of medroxyprogesterone
      acetate].
AB  - It is reported that medroxyprogesterone acetate (MPA) causes venous thrombosis as
      one of the side effects. A 49-year-old woman suffering from metastatic lung
      carcinoma from breast carcinoma was administered MPA 1200 mg/day for about four
      months. Thereafter she complained of dizziness about two weeks but the general
      practitioners could detect no abnormality on physical examinations and on brain
      CT X-ray findings. Six days later, she died suddenly at her home. Forensic
      autopsy findings revealed the marked superior sagital sinus thrombosis and the
      malignant lymphadenomatosis caused by metastatic lung carcinoma. As the patient
      had not disease or trauma causing dural sinus thrombosis except for the
      administration of MPA, we concluded that superior sagital sinus thrombosis was
      due to the medication of MPA. This case illustrates that forensic pathologist
      should consider the major side effect of some drugs like our case.

PMID- 9545763
TI  - [The influence of age and sex on the results of otosclerosis surgery].
AB  - The influence of age and sex on auditory improvement after stapes surgery was
      investigated retrospectively on 127 otosclerotic ears (99 subjects) that were
      followed up for 6 months postoperatively. The prostheses used were the Shuknecht
      type Teflon wire piston (87 ears), the House-type wire loop (29 ears), and the
      Cawthone-type Teflon piston (11 ears). While closure of the air-bone gap after
      surgery was good at 2 kHz, it was poor at 8 kHz and frequencies lower than 1 kHz,
      and especially poor at 250 Hz. At all frequencies, both air and bone thresholds
      were significantly improved by the surgery, but the greatest improvements in air
      and bone thresholds resulted from the use of Teflon wire pistons. Ears receiving
      Teflon wire prostheses were divided into 5 age groups: under 20 years, 20-29, 30
      39, 40-49, and 50 or above. Both air and bone thresholds at higher frequencies
      before surgery worsened with increasing age. However, there were no significant
      differences among age groups in the postsurgical improvement of either air or
      bone thresholds. Similarly, no gender-related differences in either air or bone
      thresholds were recognized postsurgically. The authors speculate that light cases
      of otosclerosis are common among Japanese patients, while severe cases are rare
      even among the elderly.

PMID- 9545762
TI  - Forced double suicide by fire revealed by autopsy and toxicological examination:
      a case report.
AB  - We report here a forced double suicide by fire. Two burned bodies discovered in
      the debris of a house fire were identified as a father and his son by
      odontological findings. In the father, the concentration of carboxyhemoglobin (CO
      Hb) in the left ventricle was over 90% and endrin, an organochlorine pesticide,
      was also detected in the stomach contents. However, 30.5% of CO-Hb in left
      ventricular blood and gasoline traces from an intratracheal puncture were
      detected in the son who had been undergoing treatment at a neuropsychiatric
      clinic. From these results, we determined this case to be a double suicide forced
      by the father in which the father set a fire with gasoline, thus burning his son
      to death, and then died in the fire himself after ingestion of Endrin. This case
      suggests the importance of integration of the results from the detailed forensic
      pathological and toxicological examinations and the scene investigation.

PMID- 9545764
TI  - [Facial nerve anomalies of children with congenital anomalies].
AB  - It is well known that congenital anomalies are often associated with malformation
      of the inner, middle and external ear. In temporal bone studies, it has been
      found that abnormality of the facial nerve often occurs in patients with
      congenital aberrations. The temporal bone collections of the Teikyo University
      School of Medicine include 32 human temporal bones obtained from 19 infants
      ranging in age from one day to 7 months, who had chromosomal aberration and
      severe visceral anomalies. We histologically studied routinely processed sections
      of these temporal bones under a light microscope. Facial anomaly was observed in
      20 of the 32 ears (63%). An abnormal course was observed in 18 ears (56%); 5 ears
      showed hypoplastic development, 4 showed displacement of geniculate ganglion
      cells into the internal auditory meatus, and 3 ears showed bifurcation. Abnormal
      course of the facial nerve was found in a significant number of ears with aural
      and mandibulal abnormalities (76%). However patients with multiple inner ear
      anomalies showed an abnormal course and hypoplasia of the facial nerve. There was
      no correlation between the incidence of facial abnormalities and inner ear
      anomalies.

PMID- 9545765
TI  - [Silicon of the medium in the postoperative maxillary cyst].
AB  - As part of a study on chronic inflammatory disease of the mucous membrane,
      silicon of the medium in postoperative maxillary cysts and in other cysts was
      measured, and following results were obtained. Silicon concentrations of the
      medium in the postoperative maxillary cysts and in the postoperative ethmoidal
      cysts were 34.5 ppm and 42.9 ppm (geometrical mean) respectively, and they were
      higher than in other primary cysts such as frontal cyst, nasal vestibular cyst,
      and dental cyst. The silicon content of the medium in the postoperative maxillary
      cyst varied with the water content of the medium; the lower the water content the
      higher was the silicon content and the relationship was expressed by the
      following equation. log S = 7.43 + 7.14 log d-6.14 log w, where S = Si (mcg), d =
      dry weight (g.) and w = wet weight (g.). The high concentration of silicon in the
      postoperative cyst was considered to be due to the large amount of silicon
      transudate from the surrounding fibrous tissue through a highly damaged or
      missing epithelial wall of the cyst.

PMID- 9545766
TI  - [Telomerase activity of tumors in the head and neck].
AB  - Telomerase is a maintaining enzyme of telomere repeats. Telemorase is expressed
      in immortal and cancer cells, but not in the normal tissues. We investigated
      telomerase activity of tumors in the head and neck. Telomerase activity was found
      in all of the cell lines derived from squamous cell carcinomas of the head and
      neck. Six of 9 (67%) primary fresh tissues from squamous cell carcinomas of the
      head and neck contained detectable telomerase activity. There were no apparent
      relationship between telomerase activity and clinical stage. Telomerase activity
      differed, depend on the responses to chemotherapy and radiotherapy: complete
      response, 0 of 3(0%); partial response; 0 of 1(0%); no change; 7 of 7 (100%).
      Therapy-resistant tumor seemed to have much telomerase activity and much
      malignant potential. In benign tumors, neither of 2 benign parotid tumors
      expressed telomerase activity, but one of 2(50%)papillomas had the telomerase
      activity. Telomerase is considered useful tumor marker for the diagnosis and
      prognosis.

PMID- 9545767
TI  - [Cyclin D1 overexpression in laryngeal carcinomas].
AB  - Overexpression of cyclin D1 has been found in a variety of malignancies and is
      suggested to be related to tumor progression. We immunohistochemically
      investigated the overexpression of cyclin D1 protein in 92 laryngeal carcinomas.
      Twenty-eight (30.4%) of the carcinoma specimens showed overexpression of cyclin
      D1. This overexpression was not related to the tumor stage, lymph node
      metastasis, or clinical outcome. However, the overexpression of cyclin D1 in
      patients with local recurrence was significantly higher than in patients with no
      recurrence. Cyclin D1 immunohistochemical staining is considered to be a useful
      marker for predicting tumor recurrence.

PMID- 9545768
TI  - [Clinical investigation of lymph node metastasis in carcinoma of the
      hypopharynx].
AB  - Carcinoma of the hypopharynx has a great tendency to metastasize to the neck. In
      addition it often metastasizes to the upper retropharyngeal lymph nodes
      (Rouviere's lymph nodes) and to the paratracheal lymph nodes. In this study, in
      order to determine the pattern of lymph node metastasis, 112 patients with
      carcinoma of the hypopharynx who had undergone bilateral radical neck dissection,
      bilateral paratracheal dissection, bilateral dissection of retropharyngeal nodes
      as an initial treatment between January 1982 and June 1997 in the Kurume
      University Hospital, were retrospectively reviewed in detail. Special attention
      was paid to retropharyngeal nodes and paratracheal lymph nodes. In N0 cases neck
      metastases were seen in more than one-quarter of the patients. Metastasis to
      retropharyngeal lymph nodes and to the paratracheal lymph nodes was seen in 5.4%
      and 12.5% of the patients, respectively. The frequency of metastasis to
      paratracheal lymph nodes had a significantly close relationship with that to the
      upper and lower jugular lymph nodes. The frequency of metastasis to
      retropharyngeal lymph nodes also had significantly close relationship with that
      to paratracheal lymph nodes, while having no relationship with that to other neck
      lymph nodes. These results suggest the following: 1) In patients with T1 or T2 PS
      type carcinoma of the hypopharynx, in which the lesion is confined unilaterally
      and is presumed to have been successfully treated by laser surgery prior to
      radiotherapy, unilateral neck dissection alone will be sufficient. In all the
      other patients with carcinoma of the hypopharynx bilateral neck dissection must
      be performed. 2) In all patients retropharyngeal lymph nodes and paratracheal
      lymph nodes should be dissected as much as possible and postoperative irradiation
      to both areas will be necessary.

PMID- 9545769
TI  - [Optokinetic nystagmus under prolonged alteration in the direction of gravity].
AB  - Optokinetic Nystagmus (OKN) exhibit different responses depending on the
      direction of gravity, with respect to head and body. In 13 normal healthy
      volunteers (10 experimental subjects and 3 controls), we studied the OKN evoked
      by horizontal and vertical stimuli, in upright, side-lateral, and repeated
      upright positions during a long time course of six test stages. Stage 1 was an
      upright sitting position. Stage 2 was a 90-degree recumbent lateral position
      immediately after Stage 1. Stage 3 was the same position as in Stage 2, but 2h
      later. Stage 4 was the same position, another 2h later (total of 4h). Stage 5 was
      a return to the upright position (the same as Stage 1) immediately after Stage 4.
      Stage 6 was a return to the same upright position, 2h after Stage 5. The results
      showed continuous modifications of OKN. A lateral tilt produced different effects
      on the horizontal and vertical optokinetic oculomotor systems. The gain in
      horizontal OKN (HOKN) decreased during Stages 2-4 with time, and returned to
      normal in Stages 5 and 6. As for vertical OKN (VOKN), the gain of upward (the
      direction by slow phase) OKN increased during Stages 2-4, and returned to normal
      in Stages 5 and 6. But the gain of downward OKN did not show any clear
      modulation. We showed that the change in gravity direction has a clear effect on
      OKN, and that it takes some time to reach the maximal and desirable level of
      modification. The difference in time-dependent modifications between HOKN and
      VOKN should be due to the difference in OKN-producing mechanisms and velocity
      storage systems.

PMID- 9545770
TI  - Staged intact canal wall tympanoplasty for treatment of middle ear cholesteatoma.
AB  - Results of surgery for middle ear cholesteatoma were investigated in 202 ears of
      197 patients who had undergone surgery by the staged intact canal wall technique.
      Surgical procedures used in the second stage for prevention of a retraction
      pocket were classified into three types: Type S1, no scutumplasty; Type S2,
      scutumplasty; Type S3, scutumplasty plus mastoid obliteration. Recurrent
      cholesteatoma was found in 9 ears (4%) and retraction pocket in 47 ears (23%).
      They occurred between 2 and 120 months (average: 26 months) after the second
      stage, most frequently at 1 to 3 years. The incidence was higher after Type S3
      surgery than after the other types, probably because the middle ear was severely
      involved in patients who were indicated Type S3 surgery. For prevention of a
      retraction pocket, bone putty and cartilage were proved to be appropriate
      materials for scutumplasty, and hydroxyapatite for mastoid obliteration. As the
      retraction pocket tended to recur in patients with the pocket at the second
      stage, these patients needed obliteration of the mastoid cavity to prevent a
      retraction pocket. Postoperative hearing was evaluated according to the criteria
      proposed by the Japan Society of Clinical Otology. Of 145 ears of the 142
      patients who were followed for more than 1 year, 118 ears (81%) the surgery was
      judged successful. The success rate in hearing was in good accordance with the
      condition of the tympanic membrane.

PMID- 9545771
TI  - [Molecular biology of hereditary dystonia].
AB  - The causative genes of hereditary dystonia (hereditary progressive dystonia, HPD;
      dopa-responsive dystonia, DRD) were discovered in 1994-1995. HPD/DRD is caused by
      the deficiency of dopamine to less than 20% of the normal level in the nigro
      striatum of the brain owing to the mutations of the dopamine synthesizing
      enzymes. Autosomal dominant dystonia (Segawa's disease) was found to be caused by
      mutations of GTP cyclohydrolase I which synthesizes tetrahydrobiopterin, the
      cofactor of tyrosine hydroxylase, by Ichinose et al. (Nature Genetics, 1994) in
      Japan. Autosomal recessive dystonia was reported to be caused by mutations of
      tyrosine hydroxylase by Ludecke et al. (Human Genetics, 1995) in Germany.
      Hereditary dystonia, especially autosomal dominant Segawa's disease can be
      completely controlled by L-dopa administration. Measurement of the activity of
      GTP cyclohydrolase I in mononuclear blood cells is useful for the diagnosis of
      Segawa's disease.

PMID- 9545772
TI  - [Bioethics in severely neurologically disturbed children].
AB  - Informed consent is essential for bioethical considerations when physicians treat
      severely neurologically disturbed children. Because these patients are immature
      for their decision-making, proxy consent must be given to their physicians by
      their guardian to accept within agreeable limits of treatments and care for them.
      Prior to obtaining the consent, given by their guardians, physicians are obliged
      to provide their guardians with necessary informations regarding patients'
      physical conditions and details of procedures for proposed treatments, as well as
      possible risks involved in these treatments and care to be provided. Clinical
      applications of bioethical considerations are given to the patients with
      following diseases: spina bifida cystica and other neural tube defects,
      congenital metabolic disorders such as cretinism and phenylketonuria, malignant
      tumors such as neuroblastoma and retinoblastoma, and intractable epilepsy.
      Bioethical considerations are also given to prenatal diagnosis for early
      discovery, diagnosis and possible treatments of severely neurologically disturbed
      fetuses.

PMID- 9545773
TI  - [The results of recent research in neurocutaneous syndromes].
AB  - Identification of NF1, TSC2 and TSC1 genes has enabled us to focus on their
      function and regulation. Evidence suggests that these genes are tumor suppressor
      genes. Malignant tissues in NF1 and hamartomatous tissues in TSC show "loss of
      heterozygosity" in NF1 and TSC1, 2 genes, respectively. In addition, in the Eker
      rat with hereditary renal carcinoma, a mutation in the TSC2 gene has been
      identified. In this review I mentioned briefly several issues to be clarified in
      the near future.

PMID- 9545774
TI  - [Pathophysiology and therapeutic approach in inflammatory demyelinating
      polyneuropathy--recent advances].
AB  - Recent advances on pathogenetic mechanism and therapeutic approach for Guillain
      Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIPD)
      were briefly reviewed. As for GBS, an axonal form has been recognized as a
      clinicopathological variant, in which Campylobacter jejuni infection and elevated
      anti-GM1 antibody tires are frequently observed. Other anti-glycolipid antibodies
      to GQ1b, GD1b and GM2 would also be significant as a determinant factor for a
      clinical phenotype. Beneficial effects of IVIg therapy and plasmapheresis have
      been established. Although CIDP has also been considered to be demyelinating
      neuropathy, axonal pathology is frequently noted, and in such cases, a
      substantial motor neuron loss is present. Clinical recovery in the cases with
      high anti-MAG and anti-SGPG titers is not necessarily favorable. Corticosteroid
      therapy, plasmapheresis and IVIg have been all established as therapies
      beneficial for CIDP.

PMID- 9545776
TI  - [The progress and strategy of molecular diagnosis for human genetic diseases].
AB  - Recently, the human genome project has progressed and the responsible genes for
      many diseases have been discovered. Molecular diagnosis based on gene analysis
      techniques has developed. In this paper, the methods in molecular diagnosis were
      explained, taking as examples of several pediatric neurological diseases such as
      GM1- gangliosidosis, fragile X syndrome and congenital myotonic dystrophy. Next,
      we stressed the importance of the study on the gene function in related to the
      gene mutation. Finally the strategy to establish the molecular diagnosis of
      polygenic diseases, such as mental retardation and autism, was considered.

PMID- 9545777
TI  - [Molecular analysis of peroxisomal disorders].
AB  - Peroxisome biogenesis disorders (PBD) include Zellweger syndrome (ZS), neonatal
      adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD). They are
      classified into ten complementation groups. Five pathogenic genes have been
      identified using different model systems of peroxisome deficient mutants. PAF-1
      and 2 were identified from CHO mutants and were responsible genes for PBD group F
      and C. Human PEX 5, 12 and 1, responsible genes for group 2, 3 and 1,
      respectively, were cloned by homology search between yeast PEX genes and human
      genes on the cDNA data base. Adrenoleukodystrophy (ALD), the most frequent
      peroxisomal disorder, shows phenotypic heterogeneity. Its responsible gene was
      cloned by positional cloning. It encodes a 75 kDa peroxisomal membrane protein
      (ALDP) that is a member of the ATP-binding cassette transporter family. There are
      about 120 different mutations including missense, nonsense and splice mutations,
      as well as insertions and deletions of a few base pairs. There is no correlation
      between the clinical phenotype and the ALDP gene mutation. Recently, animal
      models have been produced by targeted mutation of the PBD and ALD genes. The
      mouse model should facilitate researches on PBD and ALD, especially those on
      regulatory factors of their phenotypic heterogeneity and on new therapeutic
      approaches.

PMID- 9545778
TI  - [Molecular diagnosis of mitochondrial disorders].
AB  - Mitochondrial disorders are caused by either nuclear or mitochondrial DNA
      abnormalities. The latter but not the former can be examined as a means of
      diagnosis at present. The peculiarities and problems of the mtDNA test depend
      strongly on the characteristics of mtDNA itself, such as the multiplicity in
      number, vulnerability to mutation, and maternal transmission. The mtDNA
      abnormalities observed in patients with mitochondrial disorders indicate
      heteroplasmy, tissue/cell specificity, and threshold effects. It should be
      stressed that the presence of mutant mtDNA in an individual does not mean that he
      or she is ill. The problems of the mtDNA test could be solved if the genotype
      phenotype relationship is farther elucidated in the future study.

PMID- 9545779
TI  - [Genetic diagnosis of Duchenne/Becker muscular dystrophy; clinical application
      and problems].
AB  - Duchenne/Becker muscular dystrophies (DMD/BMD) are the most common inherited
      muscular disease and caused by mutations in the dystrophin gene. A half to two
      thirds of DMD and BMD patients carry deletions (usually of several kilobases of
      genomic DNA). The clinical progression in DMD and BMD patients with deletions can
      be predicted in 92% of cases based on whether the deletion maintains or disrupts
      the translational reading frame (frame-shift hypothesis). However, some
      exceptional cases have been reported in which some posttranscriptional
      modifications were suggested, such as alternative splicing and reinitiation of
      translation. Splicing mutation is one kind of mutations of dystrophin gene, and
      usually induced by a small mutation of exon-intron boundary sequence. However,
      intraexonal small mutation also induces exon skipping, due to disruption of an
      exon recognition sequence, which is an intraexonal sequence and necessary for
      splicing of the upstream intron. Carrier diagnosis is one of the important
      clinical application of genetic diagnosis. In the case of DMD/BMD with deletions
      of the dystrophin gene, carrier diagnosis is difficult because of the existence
      of normal X chromosome. In these cases a linkage analysis is useful, and in some
      cases non-carriers can be directly diagnosed on the basis of microsattelite
      polymorphism detected in deleted region of patient. For the molecular diagnosis
      of DMD/BMD it is important to analyze not only at the genomic DNA level, but also
      at the mRNA, protein, and clinical levels. And the relationship between the
      molecular abnormality and clinical phenotype should be examined, especially
      extramuscular symptoms such as heart failure and mental retardation.

PMID- 9545780
TI  - [GM1-gangliosidosis knockout mouse].
AB  - We generated a beta-galactosidosis mouse by gene targeting in an embryonic stem
      cell. Clinical, pathological, and biochemical analyses revealed that this mouse
      is a useful animal model to study the pathogenesis and therapy of human GM1
      gangliosidosis.

PMID- 9545781
TI  - [Topography, size and number of cortical tubers in tuberous sclerosis with West
      syndrome].
AB  - To predict the prognosis of tuberous sclerosis with West syndrome, we studied the
      relation between the cortical tubers and the neurological evolution. We reviewed
      the clinical data on the seizure evolution and developmental status of 7 patients
      (3 males and 4 females) and estimated the number, size and location of cortical
      tubers on 5 mm-thick T2-weighted MR images. The cortical tubers were grouped into
      categories: small (10 mm or less in maximum diameter), medium (10 to 25 mm) and
      large (25 mm or more). The first MRI study was performed at ages form 3 months to
      18 years, and the follow-up study was performed on 6 out of the 7 patients. We
      also estimated the interval change of cortical tubers. The average number of
      cortical tubers was 12.1 per patient, being larger than the values previously
      reported for the patients of tuberous sclerosis without West syndrome. However,
      the numbers varied widely from 1 to 29. Two patients with good outcome had more
      than 10 tubers, whereas two patients with poor outcome had less than 5 tubers.
      All the patients with good outcome were female. Follow-up MRI in one patient
      revealed a marked increase in the number of cortical tubers, from 15 (at the age
      of 5 months) to 23 (at 4 years 2 months), which probably resulted from
      physiological hypomyelination during infancy. Some tubers corresponded to a
      electroencephalographic focus, whereas others did not. There was no difference in
      the topography of cortical tubers between the patients with good prognosis and
      those with poor prognosis. Thus, it was hard to make the prognosticate a case of
      tuberous sclerosis based solely on the number and topography of cortical tubers
      on MRI.

PMID- 9545782
TI  - [Nonconvulsive status epilepticus in a patient with atypical severe myoclonic
      epilepsy in infancy].

PMID- 9545783
TI  - [Characteristics of drusen and changes in Bruch's membrane in eyes with age
      related macular degeneration. Histological study].
AB  - BACKGROUND: Different types of drusen and changes in Bruch's membrane have been
      associated with age-related macular degeneration (AMD). METHODS: We compared 51
      eyes with different stages of AMD with 40 age-matched controls using light
      microscopy. The degree of calcification of Bruch's membrane, fragmentation of
      Bruch's membrane, number of different types of drusen, and basal laminar deposit
      (BLD) were assessed. RESULTS: In the macular area, the presence of basal laminar
      deposit was most strongly associated with the presence of AMD. There was a
      statistically significant difference observed in the degree of calcification and
      fragmentation of Bruch's membrane in eyes with AMD as compared to controls. Eyes
      with AMD displayed significantly more soft, confluent, and large drusen as
      compared to controls. CONCLUSION: Calcification and fragmentation of Bruch's
      membrane, soft, confluent, and large drusen and BLD but not hard drusen
      correlated strongly with the histologic presence of AMD. Calcification and
      fragmentation of Bruch's membrane seem to facilitate ingrowth of choroidal
      neovascular membranes with consecutive development of exudative AMD.

PMID- 9545784
TI  - [Epidermal growth factor (EGF) in tears in excimer laser photorefractive
      keratectomy. Responsible for postoperative refraction and "haze"?].
AB  - BACKGROUND: Corneal wound healing is of critical importance for the postoperative
      outcome of excimer laser PRK. Wound healing is a complex biological process that
      is well characterised at the microscopic level, but its regulation is poorly
      understood at the molecular level. Among various cytokines, epidermal growth
      factor (EGF) plays an important role in superficial wound healing. The synthesis
      of EGF varies individually; therefore, by determining the EGF concentration in
      the tear fluid, patients with increased wound healing activity might be traced.
      METHODS: In this study we measured the EGF concentration pre- and postoperatively
      in the tear fluid of 50 eyes using a ELISA test. The preoperative refraction was
      between -2.00 and -10.00 dioptres. The maximum follow-up was 6 months. RESULTS:
      Preoperatively, in all eyes the EGF concentration in the tear fluid was between
      0.2 and 1.7 ng/ml. In contrast, 1 week postoperatively, these values increased
      (0.21-22.50 ng/ml); 4 weeks postoperatively, the EGF concentration was in all
      eyes back to preoperative levels. In eyes with high EGF tear fluid concentration
      1 week after surgery, refraction at 6 months was outside the intended correction
      of +/- 1.0 D. We could not find any correlation between EGF concentration and
      "corneal haze". CONCLUSIONS: EGF may play an important role in postoperative
      wound healing after excimer laser PRK. Investigations concerning a pharmaceutical
      control of EGF should be undertaken.

PMID- 9545785
TI  - [Capsular sack-fixed IOL implantation in pediatric cataract. Visual prognosis and
      complications].
AB  - BACKGROUND: The aim of the study was to evaluate results of visual acuity and
      binocularity and complications after cataract surgery with primary capsular bag
      fixated IOL implantation in children. MATERIALS AND METHODS: Thirty-three
      children [mean age (+/- SEM) 6.9 +/- 2.9 years, range 3-12 years] accounting for
      43 eyes, were examined before and after surgery (15 traumatic, 19 developmental,
      and 9 congenital cataracts, of the latter two groups 9 unilateral and 19
      bilateral cataracts). RESULTS: All eyes had a best corrected postoperative visual
      acuity of 0.5 +/- 0.05. The postoperative visual acuity of the traumatic
      cataracts was 0.6 +/- 0.07, of the developmental cataracts 0.5 +/- 0.07, and of
      the congenital cataracts 0.2 +/- 0.05. Of the 43 eyes, 17 (40%) showed a best
      corrected visual acuity of 0.5 or better. There was a positive correlation
      between morphology (lamellar versus subcapsular opacification) and visual acuity
      (0.7 +/- 0.07 versus 0.5 +/- 0.05; P < 0.05). Bilateral cataracts had a better
      postoperative visual acuity than unilateral cataracts (0.7 +/- 0.07 versus 0.2 +/
      0.05 P< 0.001) Stereopis was found postoperatively in 62% of the children. In
      one eye a capsular bag-fixated IOL implantation was not possible, and so the IOL
      was inserted in the sulcus. Four children presented with postoperative fibrin
      formation. Posterior capsule opacification occurred in 19% of the eyes in which a
      primary posterior capsulotomy had been performed. CONCLUSIONS: The prognosis of
      visual acuity and the results of stereopsis in children older than 3 years
      following capsular bag-fixated IOL implantation are very good. Both the
      intraoperative and postoperative complication rates were low.

PMID- 9545786
TI  - [Threshold-oriented suprathreshold perimetry and threshold value perimetry with
      the Tubigen CC Automated Perimeter. A comparative study].
AB  - BACKGROUND: We compared the standard suprathreshold strategy to the so-called
      threshold splitting strategy with 5 and 2 dB steps. The aim of the study was to
      establish whether the threshold splitting strategy had advantages over the
      suprathreshold strategy that has been used to date. METHOD: We examined the 30
      degrees visual field in 49 volunteers using suprathreshold perimetry and on the
      same day threshold splitting perimetry on the Tubinger Automatic Perimeter CC. A
      total of 191 test points were examined in suprathreshold strategy. Using the
      threshold splitting strategy, 67 test points were examined, with a test-point
      design similar to other perimeters with the threshold splitting strategy. The
      criteria for inclusion in the study were central light sensitivity differences
      greater than 25 dB, fixation better than 80% and an illumination class density <
      2. RESULTS/DISCUSSION: The average duration of the examination using the
      suprathreshold strategy was 2-3 min quicker than the threshold splitting strategy
      in normal visual fields or small scotomas, but it took up to 15 min longer if
      large scotomas were presents. Interpretation of the scotoma configuration showed
      subjective differences: the smaller the scotoma, the greater the differences
      because of the fact that threshold splitting perimetry utilizes test points that
      are farther apart than those used in suprathreshold perimetry.

PMID- 9545787
TI  - [Risks of 360 degree suture trabeculotomy].
AB  - BACKGROUND: In 1995, Beck and Lynch reported a method to perform a 360 degrees
      trabeculotomy by prolene suture introduced into Schlemm's canal. Because this
      type of surgery has proved to have perils and can lead to extreme hypotony, even
      a small series of cases must be reported. PATIENTS: Suture trabeculotomy was
      planned in five eyes of four patients, 5 and 7 months old and 6 and 51 years old,
      with primary congenital glaucoma, but completed in only two eyes. RESULTS: In one
      child, suture trabeculotomy could be accomplished easily in both eyes. In the
      first eye a 360 degrees-tomy was performed, in the second eye only a 180 degrees
      tomy was done. Both eyes remained extremely hypotonic (4 mm Hg). In one eye
      Schlemm's canal could not be disrupted by the suture; in another eye, Schlemm's
      canal could be probed only for a short distance, and in one eye the suture went
      the wrong way. CONCLUSIONS: Because a suture trabeculotomy can be transformed
      into a normal trabeculotomy any time, the main problems of the 360 degrees-suture
      trabeculotomy are not the possible technical difficulties, but that a successful
      suture trabeculotomy is followed by extreme hypotony.

PMID- 9545788
TI  - [Imaging the tear film and in vivo cornea. Initial results with a modified
      confocal laser scanning ophthalmoscope].
AB  - BACKGROUND: As the slit-lamp technique is an restrictive method for the in-vivo
      examination and documentation of the multi-layer structure and the dynamics of
      the tear film and the cornea, e.g. during wound-healing processes, our aim was to
      find out whether it is possible to change the confocal laser scanning
      ophthalmoscope (CLSO; Zeiss) into a high-resolution confocal laser scanning
      microscope (CLSM) for the visualization of the anterior segments of the eye and
      the tear film by adapting a special objective system. In order to gain
      information concerning the function of such a cornea microscope we examined
      selected patients with erosion or pterygium before and after operation and
      subsequent phototherapeutic keratectomy (PTK), as well as some in-vitro corneal
      surfaces after photorefractive keratectomy (PRK). MATERIAL AND METHODS: We
      developed an objective adapter for the CLSO in order to focus the laser beam onto
      anterior segments of the eye to visualize the tear film and the layer structure
      of the cornea. By combining the long-distance objective or a contract objective
      with different zoom-optic lenses it was possible to alter the scan field size and
      so the magnification of the CLSM by a factor of up to 1000. RESULTS: The CLSM
      provides a new method for the in-vivo examination of the tear film and its
      dynamics as well as the thin layers of the cornea in real-time imaging technique
      with high contrast and resolution in non-contact or contact procedures.
      CONCLUSION: This system is a unique took for evaluating and monitoring the effect
      of excimer laser ablation after PTK and PRK on the corneal surface and the
      dynamics of the tear film. The application of this method causes no pain for the
      patient.

PMID- 9545789
TI  - [Image flicker frequency of television reading aids. Effect on reading comfort
      for visually handicapped patients].
AB  - PURPOSE: To compare reading speed and reading comfort between closed-circuit
      television systems (CCTVs) with different image refresh rates. METHODS: Reading
      speed was measured with three CCTVs that only differed in repeat frequency (50,
      60 and 70 Hz) in 21 patients with age-related macular degeneration and 10
      controls. We compared reading speed measured in syllables per minute of 16
      different reading templates with about 500 syllables each. RESULTS: Reading speed
      was equal with all CCTVs. Eighteen of 21 patients identified and disliked 50 Hz
      CCTVs because the image quality was worse. An image quality of 70 HZ enabled
      patients to use positive contrast with the best reading speed. CONCLUSIONS:
      Although reading speed does not improve with increasing frequency, flickering of
      50 Hz CCTVs is critical for low-vision patients. The preference of low-vision
      patients for negative contrast image is more likely due to flickering with a
      lower repeat rate and 70 Hz CCTVs may allow more comfortable reading in positive
      contrast.

PMID- 9545790
TI  - [Transplantation of amniotic membrane for reconstruction of the eye surface].
AB  - Persistent defects of the ocular surface remain a therapeutic challenge that
      often requires surgical intervention. Recently, the transplantation of human
      amniotic membrane has been added to our therapeutic armentarium. This thick
      basement membrane has distinct biological properties that influence cellular
      differentiation and proliferation. Amniotic membrane obtained from cesarean
      deliveries is prepared and cryopreserved under sterile conditions and can be
      sutured onto the ocular surface. This procedure allows for reepithelialization of
      persistent corneal ulcerations as well as filling of stromal defects. Amniotic
      membrane can successfully be employed for ocular surface reconstruction following
      large corneal excisions and in the context of limbal stem cell disease for
      pterygium surgery as well as for various kinds of reconstruction of the
      conjunctiva. Taken together, amniotic membrane transplantation can serve as a
      valuable tool for ocular surface reconstruction, especially in the context of
      impaired epithelial function.

PMID- 9545791
TI  - [Comment on the contribution by C.-D. Quentin and H. Reiber: Aqueous humor
      analysis in intraocular toxoplasmosis].

PMID- 9545792
TI  - [Swelling in the area of a scar after injury to the orbital wall. Occult foreign
      body].

PMID- 9545793
TI  - [Immune privilege of the eye].

PMID- 9545794
TI  - [Current principles of diagnosis and treatment of chronic lymphocytic B-cell
      leukemia].
AB  - Chronic lymphocytic leukaemia is the most frequent form of malignant
      hematological diseases in the Western countries, it comprises 30-40% of all the
      leukaemias and it manifests itself between 60-65 years of age. Clinical features
      are caused in 93% of the cases by the accumulation and proliferation of
      immunologically incompetent, anergic, long lived, CD5 positive B-lymphocytes,
      expressing monoclonal IgM or IgD immunglobulin, in the bone marrow, the
      peripheral blood, the lymphoid and in other organs. In the etiology genetic basis
      is highly supposed, whereas affect of toxic agents and radiation exposure can be
      neglected. The prognosis of patients is variable and is determined by the
      clinical stage and the proliferative activity of the disease. Treatment is
      indicated in intermediate and high-risk clinical stages only with signs of
      disease activation on the basis of individual patient's risk. As first line
      treatment, Chlorambucil is indicated in high doses. Results achieved by combined
      chemotherapy are generally not superior compared to high-dose Chlorambucil
      treatment. For patients who developed resistance to alkilating agents purin
      analogues are recommended. Out of them the most favorable results had been
      accumulated with Fludarabine as second line treatment. For minority of the cases
      hemopoetic stem cell transplantation as the only curative therapeutic measure is
      being introduced in an increasing number. This review gives an account of the
      recent advances in the diagnosis and therapy of the disease.

PMID- 9545795
TI  - [Assessment of cerebrovascular reactivity in patients with symptomatic and
      asymptomatic atherosclerotic carotid artery lesions].
AB  - AIMS: Strokes caused by hemodynamically significant internal carotid artery
      stenoses and occlusions are believed to be embolic or hemodynamic of origin. The
      aim of the study was to assess cerebral hemodynamic compromises of significant
      carotid artery stenosis of occlusion using vasodilatory testing (acetazolamide
      test) in asymptomatic and symptomatic patients. PATIENTS AND METHODS: 36 patients
      with unilateral, hemodynamically significant carotid stenosis were investigated
      using transcranial Doppler acetazolamide-test. There were 12 asymptomatic and 24
      symptomatic patients. The middle cerebral artery mean blood flow velocity was
      measured at rest and after intravenous injection of 1 g acetazolamide. The
      absolute mean blood flow velocities and the cerebrovascular reactivity was
      compared at the stenotic and non-stenotic side. In a further analysis the mean
      velocities and the cerebrovascular reactivity values of the stenotic side were
      compared. Results of acetazolamide test performed on 28 healthy volunteers were
      used as control values. RESULTS: There were no side-differences between the
      middle cerebral artery mean blood flow velocity and cerebrovascular reactivity
      values in the asymptomatic group. In the symptomatic group, however middle
      cerebral artery mean velocity and cerebrovascular reactivity after acetazolamide
      was significantly lower on the stenotic side, than on the non-stenotic one.
      Comparing the different groups non-stenotic sides did not differ to each other in
      their cerebral blood flow velocity and cerebrovascular reactivity. In the
      symptomatic patients, however, cerebral blood flow velocity and cerebrovascular
      reserve capacity after acetazolamide was lower, than that of the stenotic side of
      asymptomatic patients and controls. CONCLUSIONS: The transcranial Doppler is a
      suitable method for detecting altered cerebral hemodynamics in significant
      carotid stenosis. Impaired cerebrovascular reactivity may refer to the impairment
      of cerebral autoregulatory mechanisms.

PMID- 9545796
TI  - [Endoscopic subfascial vein dissection].
AB  - Endoscopic subfascial dissection is an effective method for the interruption of
      incompetent perforating veins. From 15th October to 15th December of 1995 11
      patients underwent endoscopic subfascial sectioning. It is the first time to
      apply this procedure in Hungary. A venous ulcer was found in 5 patients.
      Endoscopic sectioning supplemented by extensive fasciotomy, without any
      substantial complication. The method is recommended due to its reduced
      invasiveness and fair results.

PMID- 9545797
TI  - [Regulation of the cell cycle].
AB  - The basic steps of the eukaryotic cell cycle process have been known for almost
      half a century. The development of the molecular biological methods allowed the
      identification of the cell cycle regulatory genes and their products. The cycline
      dependent kinases as catalytic subunits of the multiprotein nuclear enzyme
      complexes, regulate the cell cycle machinery in a direct way in complex with the
      cyclins which appear periodically and the negatively modulating cyclin
      inhibitors. To assure strategy of the cell for global survival during the DNA
      injury, the Ataxia Teleangiectasia Mutator gene function has a supervisory role
      in the coordination and parallel activation of the checkpoint control, p53 tumor
      suppressor gene, GADD45 protein and of the DNA repair, thus prevents the
      activation of the cell death program. The outlined regulator system gives an
      opportunity to explain some of the phenomena related to tumor biology and
      pharmacology.

PMID- 9545799
TI  - [Pathogenesis of ophthalmopathy].

PMID- 9545798
TI  - [Severe genital mycoplasma infection following cesarean section].
AB  - Authors report a serious case of post-caesarean delivery endometritis caused,
      probably exclusively, by genital mycoplasmas: Ureaplasma urealyticum and
      Mycoplasma hominis. The initial treatment of the patient with various
      penicillins, ceftriaxone, gentamicin, metronidazole and nystatine proved
      ineffective. Subsequently, as microbiological tests turned out positive for
      genital mycoplasmas, a therapy of doxycyclin was introduced and a full recovery
      could be attained. Authors' experience is consistent with the observation of
      American scientists that U. urealyticum is an important pathogen in post
      caesarean delivery endometritis. Since the carriage of U. urealyticum in women is
      frequent in Hungary, it is suggested that microbiological investigations related
      to sectio caesarea always include tests for genital mycoplasmas.

PMID- 9545800
TI  - [Questions about scientometry].

PMID- 9545801
TI  - [FISH, interphase cytogenetics, gene rearrangements].

PMID- 9545802
TI  - [Future development of platelet transfusion].

PMID- 9545803
TI  - [Signal transduction BCR-ABL fusion protein: analysis of BCR-ABL functional
      domains].

PMID- 9545804
TI  - [Internal tandem duplication in the juxtamembrane domain of the Flt3 gene found
      in leukemias].

PMID- 9545806
TI  - [Constitutive activation of B cell antigen receptor-associated tyrosine kinases
      in B cell leukemia/lymphoma lines].

PMID- 9545805
TI  - [Constitutive activation of MAP kinase pathway and STAT pathway in AML].

PMID- 9545808
TI  - [Regulation system of apoptosis contributes to the human pro-B leukemogenesis].

PMID- 9545807
TI  - [Overexpression of differentiation inhibitory factor/nm23 in acute myeloid
      leukemia].

PMID- 9545809
TI  - [Scoring systems for predicting prognoses of the patients with AML treated
      according to the Japan Adult Leukemia Study Group (JALSG) protocols].

PMID- 9545810
TI  - [Short-term intensive therapy for adult AML].

PMID- 9545811
TI  - [Leukemia specific chimeric protein as a target molecule for chemotherapy].

PMID- 9545812
TI  - [Individualized treatment of leukemia patients by monitoring of minimal residual
      disease (MRD) based on WT1 assay].

PMID- 9545813
TI  - [Is the ABVD an optimal regimen for Hodgkins disease?].

PMID- 9545814
TI  - [Long-term follow up of aggressive lymphoma patients treated with CAMBO-VIP-
      clinical significance of a residual mass after otherwise successful
      chemotherapy].

PMID- 9545816
TI  - [Clinical significance of platelet-derived microparticles in thrombotic disease].

PMID- 9545815
TI  - [Interaction between platelets and oxidised-lipid in thrombus formation].

PMID- 9545817
TI  - [Basis of molecular cell biology on thrombosis: in the cases of protein C
      deficiency and protein S deficiency].

PMID- 9545818
TI  - [Potential mechanisms of thrombogenesis in antiphospholipid syndrome].

PMID- 9545819
TI  - [Fluid shear stress-mediated signal transduction in endothelial cells: temporal
      signaling events].

PMID- 9545820
TI  - [Adenovirus-mediated local expression of TFPI eliminates shear stress-induced
      recurrent thrombosis in the injured arteries].

PMID- 9545821
TI  - [Molecular analysis and gene therapy in Fanconi anemia].

PMID- 9545822
TI  - [Gene analysis of hereditary red cell membrane disorders].

PMID- 9545823
TI  - [Prospects for gene therapy for chronic granulomatous disease with gp91-phox
      deficiency].

PMID- 9545824
TI  - [Mutation of WASP in Wiskott-Aldrich syndrome and it's effect on
      megakaryopoiesis].

PMID- 9545825
TI  - [Mechanism of tumorigenesis and cell cycle dysregulation in ataxia
      telauqiectasia].

PMID- 9545826
TI  - [Molecular analysis of hemophilia A].

PMID- 9545827
TI  - [Severe hepatic veno-occlusive disease (VOD) which was successfully treated with
      supportive therapy, but subsequently developed late-recurrence].
AB  - A 40-year-old man with chronic myelogenous leukemia in chronic phase received an
      allogeneic marrow graft from his HLA identical brother. He was conditioned with
      busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). Graft-versus-host disease
      (GVHD) prophylaxis was attempted with cyclosporine A (CYA) and methotrexate. On
      day 30, weight gain, ascites and hepatomegaly developed in addition to an
      elevation of total bilirubin (TB). He was diagnosed as having veno-occlusive
      disease (VOD) and treated conservatively. The TB level increased up to 20.1 mg/dl
      on day 66, then reduced to 2.1 mg/dl on day 129. By that time ascites and
      hepatomegaly also had completely resolved. However, on day 134. The TB level
      started to increase again, when the lesions of chronic GVHD were observed in the
      eye, the mouth, and the skin. CYA was started on day 142, and FK506 was
      substituted for CYA on day 161. Despite the improvement of oral and skin lesions,
      TB level continued to rise, and he died of respiratory failure due to ARDS on day
      186. Autopsy revealed both acute and old hepatic VOD lesions, suggesting the
      occurrence of late-onset VOD which probably contributed to the liver dysfunction
      observed after clinical resolution of the first episode of VOD.

PMID- 9545829
TI  - [Fatal pulmonary thromboembolism in a patient with paroxysmal nocturnal
      hemoglobinuria].
AB  - A 38 year old woman with paroxysmal nocturnal hemoglobinuria was admitted to our
      hospital because of hemoptysis. Pulmonary infarction was diagnosed by the
      perfusion lung scan. In spite of the administration of prednisolone, dextran, low
      molecular weight heparin, and warfarin, she died of pulmonary infarction and
      secondary pulmonary hypertension. Autopsy revealed thromboembolism of both
      pulmonary arteries and hepatic central vein thrombosis. Recent understanding of
      the pathogenesis and incidence of thromboembolism in paroxysmal nocturnal
      hemoglobinuria was discussed.

PMID- 9545828
TI  - [Abnormal hemoglobinopathy (HbE) diagnosed from microcytic hypochromic red blood
      cells in a 31 year-old Bangladeshian male].
AB  - Microcytic hypochromic red blood cells (RBC) were discovered in a 31 year-old
      Bangladeshi man. Additional laboratory data revealed only slight elevations of
      LDH and transaminase activities. The patient was clinically asymptomatic and
      showed no signs of anemia. On this basis, along with biochemical genetic analysis
      of hemoglobin, a diagnosis of hemoglobinopathy (HbE) was made. HbE is common in
      southeast Asia with over 30% of the population affected. Most people are
      asymptomatic. In northern Asia, including Japan, HbE is found in only 0.001% of
      the population. With ther recent influx of southeast Asians to Japan, care must
      be taken not to overlook the diagnosis of hemoglobinopathies.

PMID- 9545830
TI  - [Successful syngeneic peripheral blood stem cell transplantation for protracted
      myelosuppression after chemotherapy in a patient with acute myelogenous
      leukemia].
AB  - Acute myelogenous leukemia (M2) with translocation of 8;21. Was diagnosed in 61
      year-old man. He was successfully treated and obtained complete remission. After
      consolidation therapy, myeloid suppression and maturation arrest at the myelocyte
      level were recognized. Following intensive chemotherapy, he received rhG-CSF
      mobilized peripheral blood stem cell transplantation (PBSCT) from an identical
      twin because he had life threatening infectious events and protracted
      myelosuppression. Transplantation of 2.5 x 10(6)/kg CD34+ cells resulted in a
      rapid normal tri-lineage hematologic reconstitution. Syngeneic PBSCT appears to
      be a substitute for syngeneic bone marrow transplantation in certain situations.

PMID- 9545831
TI  - [Pharmacologic pain treatment].
AB  - Pharmacotherapy of chronic pain uses the following groups of drugs: simple
      analgesics, NSAID's, opioids, calcitonin, antidepressants, neuroleptic drugs and
      myorelaxants. Diseases of the locomotor system are very often chronic or
      chronically recurrent. We therefore need a tailored longterm therapy. We have to
      consider not only the effect but also side effects of the different drugs. The
      aim of the therapy is an optimal quality of life for the individual patient. To
      this end we have to avoid polypragmasia.

PMID- 9545832
TI  - [Opioids in treatment of chronic noncancer pain].
AB  - Opioids have been accepted as appropriate analgesic treatment for pain associated
      with cancer. However, controversy exists about their use for chronic noncancer
      pain. Reasons for reluctance are concerned about efficacy and potential adverse
      effects such as respiratory depression, addiction, physical dependence or
      intolerance. Many physicians worry about liability and legal restrictions.
      Nevertheless, pain management of chronic severe pain with opioids can be the only
      help when alternative methods are too risky of fail to be effective. This article
      briefly reviews the published literature on this topic and discusses some
      practical guidelines for the use of opioids in the treatment of non-cancer pain.

PMID- 9545833
TI  - [Sacral block: indications and effectiveness].
AB  - It has been shown that during injection of 17 to 20 ml local anesthetics combined
      with a corticosteroid via the hiatus canalis sacralis that the solution is
      distributed up to the level of the thoraco-lumbar junction. The indication for
      therapeutical peridural injection are radicular symptoms as a result of disc
      herniation, foraminal stenosis as well as neurogenic claudicatio.
      Contraindications are anticoagulation, local infection as well as suspicion of
      systemic inflammatory disease of the peripheral nervous system. With proper
      technique and adequate desinfection, complications and side effects are very
      rare.

PMID- 9545834
TI  - [Manual medicine in pain treatment].
AB  - To diagnose the source of pain, a very refined segmental technique is employed in
      manual medicine. The evaluation of static and dynamic functions is complemented
      by palpatory and functional testing of the joint mechanics. A reversible
      hypomobility of a joint causes a swelling of the surrounding soft tissue, a
      stiffening of the muscle tissue and a change in turgor and trophicism. The
      various techniques of manual medicine restore the physiological joint play,
      causing thereby reflectory phenomena, often the source of pain, to disappear
      quickly. Trivial trauma or inappropriate coordination of movement sequences
      interfere with joint mechanics. The nociceptive stimulus from all joint
      structures activates segmentally connected muscular fiber bundles through the
      posterior horn complex via alpha- and gamma-motoneurons. The joint play of other
      segments and/or peripheral components can be disturbed via interneurons and
      become a source of pain. Mobilisation of the joint activates inhibitory neurons,
      the normal joint mechanics are reestablished and the nociceptive stimulus
      reduced.

PMID- 9545835
TI  - [Intracerebral neurosurgery in the treatment of chronic pain].
AB  - Brain surgery is generally considered a treatment of last resort for chronic pain
      resistant to all other therapeutic measures. The neurosurgical treatment of pain
      may be either destructive (e.g., thalamotomy) or augmentative (e.g., electrical
      stimulation through an electrode connected to an implanted neurologic pacemaker).
      For pain of the neurogenic type (neuropathic or deafferentation pain), the
      preferred target is either the sensory nucleus of the thalamus, at a site
      corresponding somatotopically to the location of the pain, or the precentral
      cortex. For somatic (nociceptive) pain, stimulation of the periventricular or
      periaqueductal gray matter, or intraventricular infusion of morphine, may be
      useful. These operations are now indicated only in exceptional cases, as will be
      explained with reference to the author's long experience.

PMID- 9545836
TI  - [Febrile state, bloody diarrhea and megacolon].
AB  - We report about a forty year old female patient with severe bloody diarrhoea and
      fever over a period of 14 days due to an infection with Salmonella enteritidis. X
      ray of the abdomen showed a toxic megacolon. With the diagnosis of an infectious
      colitis we started therapy with ciprofloxacin i/v. The toxic megacolon progressed
      despite intensive care and parenteral nutrition. Additionally the patient
      received metronidazole i/v and in combination with a roll technique in bed in the
      knee-elbow-position the leucocytosis and the megacolon decreased. A toxic
      megacolon is in about 3% associated with an infection with Salmonella
      enteritidis. It is essentially diagnosed by X-ray. Patients should receive
      intensive care, and because of the high mortality rate an interdisciplinary
      management is required. The article discusses the major differential diagnosis of
      the toxic megacolon, as well as the pathogenesis and therapy of Salmonella ent,
      infection. In case of an infection with Salmonella ent. physicians should
      acknowledge the possibility of development of a toxic megacolon.

PMID- 9545837
TI  - [Stage II sarcoidosis].

PMID- 9545838
TI  - [What is your diagnosis? Information regarding the examination of his daughter
      (virginity)].

PMID- 9545839
TI  - [Generic drugs: curse or blessing?].

PMID- 9545840
TI  - [Value of thoracoscopy and talc pleurodesis in diagnosis and palliative treatment
      of malignant pleural mesothelioma].
AB  - Malignant pleural mesothelioma (MPM) remains a disease of very poor prognosis
      despite all new therapeutic approaches. We describe here 13 cases with MPM. The
      main symptoms at presentation were dyspnea (12/13) followed by weight loss
      (7/13), cough (3/13) and thoracic pain (2/13). On chest X-ray, all patients had
      pleural effusion associated with pleural thickening in 8/13 cases (62%). A
      definitive diagnosis was brought by thoracoscopy in 11/12 cases (diagnostic
      sensitivity 92%). In one patient, thoracoscopy was technically impracticable
      because of very important obesity. By thoracoscopic talc pleurodesis, we were
      able to control the pleural effusion in all patients with suppression of dyspnea
      (11). The mean survival after diagnosis was 6.8 +/- 5.0 months (range 1-16). At
      the present time, we believe that thoracoscopy is well indicated in any suspicion
      of MPM not only for diagnosis but also for palliative treatment of this pleural
      disease. However, there is a need for well controlled studies to improve the
      outcome of MPM.

PMID- 9545841
TI  - [Iatrogenic disease and self-injury: significant factors in hospital admission?].
AB  - The frequency of adverse effects caused by doctors may serve as a quality
      control. We therefore assessed the number of adverse effects leading to a
      hospital admission and occurring during a six-month period in the medical
      department of a district hospital. We compared these figures with the number of
      admissions caused by substance-abuse by the patient himself. RESULTS: At
      admission to hospital 35 patients (6.4%) suffered from adverse effects. In 89% of
      these, the adverse effect was the leading factor to admit the patient; in the
      remaining 4 patients (11%) the adverse effect was detected by routine-screening
      upon admission. Further 8.6% developed adverse effects in the hospital which in
      12.5% had consequences upon course and duration of the hospitalization. Self
      afflicted hospital-admissions (substance-abuse, suicide-attempts) were found in
      13%. Iatrogenic adverse effects brought 3.5% of the patients to the hospital.
      CONCLUSIONS: Adverse effects caused by diagnostic and therapeutic activities of
      doctors considerably contribute to hospital-admissions and course of hospital
      stay, but even more often the patient himself is responsible by his self-damaging
      behavior.

PMID- 9545842
TI  - [Withdrawal syndrome caused by selective serotonin reuptake inhibitors: apropos
      of a case].
AB  - During the past 4 years, several case reports have been published on the
      withdrawal syndrome which may be observed after acute interruption of a treatment
      with selective serotonin reuptake inhibiting antidepressants (SSRI). Paroxetine
      is the most frequently cited antidepressant in the literature, whereas fluoxetine
      is the less frequently cited of this type of drugs. The withdrawal symptoms
      appear a few days after stopping treatment or after a decrease of the dose. The
      typical symptoms are of the gastro-intestinal type, such as loss of appetite,
      nausea, vomiting, diarrhea and abdominal cramps. Other symptoms are sensation of
      instability, vertigo, dizziness, headache, malaise, muscular pains, asthenia, as
      well as a syndrome of pseudo-influenza. Brief electric shocks throughout the
      body, which last one or two seconds, have also been reported. A case is reported
      in detail by the authors, who observed some of these symptoms in a patient after
      stopping his treatment with paroxetine. This withdrawal syndrome may be due to a
      rebound phenomenon of the serotonergic systems after interruption of the
      treatment with SSRIs. It is, therefore, recommended that treatment with SSRIs is
      progressively stopped over a period of several weeks.

PMID- 9545843
TI  - [Abdominal pain and flatulence. Intestinal and pulmonary tuberculosis. IgG kappa
      paraproteinemia].
AB  - A 21-year-old woman suffered from cramplike abdominal pain, flatulence and
      occasional diarrhoea for about one year. Over the past few weeks the abdominal
      symptoms exacerbated, besides productive cough and subfebrile temperatures
      developed. Coloscopy revealed two isolated, short ulcers in the proximal colon.
      The histological examination of the biopsies taken from these ulcers indicated
      granulomatous inflammation. Moreover small acinar infiltrates in both pulmonary
      apices were visualized. The findings in this patient originating from Turkey were
      suspicious for intestinal and pulmonary tuberculosis. Though sensitive methods
      were used (Ziehl-Neelson stam, amplified M. tuberculosis direct test, a
      polymerase chain reaction) direct tests allowed no detection of mycobacteria.
      Antituberculous therapy was initiated on a probatory basis to which the patient
      responded well and promptly. The diagnosis was confirmed by culture results: M.
      tuberculosis was grown from colonic biopsies, morning sputa and bronchioalveolar
      lavage.

PMID- 9545844
TI  - [Ascites. Tuberculous peritonitis].
AB  - Because of deteriorating general health, weight loss of 5 kg and leftsided
      epigastric pain a 44 year old innkeeper was evaluated unsuccessfully for 1 month.
      Thereafter a protein- and lymphocyte-rich ascites developed. CT-scans revealed a
      thickened visceral peritoneum and multiple, marginally increased retroperitoneal
      lymph nodes. The history of the patient originating from former Jugoslavia was
      suspicious for inadequately treated tuberculous pericarditis. Hence this
      diagnosis tuberculous peritonitis became probable but for practical reasons could
      not be proven neither by biopsy nor by culture. Under probatory antituberculous
      treatment the patient's general condition improved rapidly, the ascites
      disappeared and initially elevated parameters for infection normalized.

PMID- 9545845
TI  - [Increase in transaminases in HIV infection. Toxic liver cell damage with
      trimethoprim/sulfamethoxazole administration in HIV infection].

PMID- 9545846
TI  - [Surgical and conservative treatment of liver diseases].

PMID- 9545847
TI  - [Therapy of viral hepatitis].
AB  - The therapy of viral hepatitis has great medical and socioeconomic impact. Today
      chronic viral hepatitis is the most important cause for chronic liver disease,
      liver cirrhosis, and hepatocellular carcinoma. Hepatitis A and E cause acute
      courses exclusively whereas infection with the hepatitis B, C, and D virus might
      result in chronic hepatitis as well. The goal of therapy of chronic viral
      hepatitis has to be a reduction/normalisation of elevated transaminases, decrease
      of the serologic parameters of active viral replication, improvement of histology
      and prevention of complications of chronic hepatitis. The only drug with proven
      benefit in the treatment of chronic viral hepatitis is interferon alpha. This
      therapy results in a sustained response in 25 to 40% for hepatitis B and 10 to
      25% for hepatitis C infection. New developments under clinical evaluation are
      Lamivudine and Famciclovir in the treatment of HBV-infection and Ribavirin in
      combination with INFa for chronic HCV-infection.

PMID- 9545848
TI  - [Treatment of alcoholic liver diseases and psychiatric and psychosocial
      problems].
AB  - Only about 15% of the subjects abusing ethanol will eventually develop cirrhosis
      of the liver, suggesting that other factors in addition to the consumption of
      large quantities of ethanol play a role in the pathogenesis of alcoholic
      cirrhosis. Important contributors may be infection with hepatitis viruses, in
      particular HCV, protein-calorie malnutrition and immunologic factors. Abstinence
      improves the prognosis of patients with alcoholic cirrhosis, provided that the
      liver disease is not too far advanced. No pharmacotherapeutic intervention has
      shown a convincing improvement of the prognosis of alcoholic liver disease, so
      that the therapeutic efforts should be mainly directed towards abstinence. The
      patient with alcoholic liver disease needs support and guidance by the treating
      physicians. Supportive treatment with Disulfiram, Acamprosate or Naltrexon can
      help with achieving durable abstinence.

PMID- 9545849
TI  - [Non-surgical treatment of portal hypertension].
AB  - The choice of methods for the treatment of acute variceal hemorrhage critically
      depends on the locally available expertise. Vasoactive drugs or balloon tamponade
      may bridge the time to more definitive measures such as sclerotherapy or band
      ligation. Drugs (nonselective beta-adrenergic blockers and long-acting nitrates)
      are almost equivalent to endoscopic sclerotherapy for the prevention of recurrent
      bleeding, while band ligation offers both increased efficacy (reduced rate of
      rebleeding and death) and decreased complication rates when compared to
      sclerotherapy. Thus, ligation will predominantly be used for the prevention of
      recurrent bleeding. Alternatively, drugs may be applied when acute bleeding was
      effectively stopped without the use of endoscopic means. Endoscopic sclerotherapy
      and surgery have no place in the primary prophylaxis of variceal hemorrhage in
      patients who have not bled before. Prevention of the first bleed is clearly the
      field for beta-blockers or nitrates. The role of banding ligation in this
      situation remains to be defined.

PMID- 9545850
TI  - [Treatment of portal hypertension by portosystemic shunts].
AB  - The use of shunts for the treatment of portal hypertension has been revived after
      the introduction of the transjugular intrahepatic portosystemic shunt (TIPS) into
      clinical practice. This interventional procedure has mainly been used as rescue
      treatment for variceal bleeding resistant to endoscopic therapy and for ascites
      refractory to diuretic treatment and paracentesis. With respect to variceal
      bleeding TIPS has a low rate of "operative" mortality of < 1% and variceal
      rebleeding of 6 to 18%. In patients with refractory ascites the response to
      treatment is 50 to 92%. The major problems of the TIPS procedure are the
      increased incidence of hepatic encephalopathy and the high rate of shunt
      insufficiency of about 50%. Therefore, control of shunt function by duplex
      sonography is essential to detect malfunction of the shunt. Radiological revision
      is then indicated if the clinical symptoms of portal hypertension (varices,
      ascites) reappear. The TIPS treatment has partially replaced the surgical
      shunting procedures. This decision is based on the potentially higher mortality
      of the surgical procedure. However, this has not been proven by randomized
      studies and, therefore, surgical shunts may also be indicated in selected
      patients with low operative mortality.

PMID- 9545851
TI  - [Cholestasis: therapeutic options].
AB  - Ursodeoxycholic acid (UDCA) has been shown to be both an effective and well
      tolerated treatment of primary biliary cirrhosis, a model chronic cholestatic
      liver disease. Beneficial effects of UDCA have also been observed in other
      cholestatic disorders such as primary sclerosing cholangitis, cystic fibrosis, or
      intrahepatic cholestasis of pregnancy. Liver transplantation is the treatment of
      choice in end stage chronic cholestatic liver disease. Symptomatic therapeutic
      concepts include the treatment of cholestasis-associated problems such as
      pruritus, osteopathy and vitamin deficiency.

PMID- 9545852
TI  - [Diagnosis and therapy of obstructive jaundice].
AB  - Obstructive jaundice is a sign of intra- or posthepatic blockage of bile flow.
      This diagnosis has to be differentiated from various other diagnoses such as
      disorders of bilirubin metabolism or hepatocellular causes of jaundice. An
      accurate evaluation of the past medical history and clinical examination of the
      patient can already establish obstruction as the cause of jaundice in most cases.
      For prevention of a cholangitis further imaging procedures should focus on
      rapidly establishing the cause and the location of obstruction. Further
      therapeutic procedures are dependent on the type of obstruction and the condition
      of the patient. Most importantly there should be a decompression of the biliary
      tree with ES or PTBD.

PMID- 9545853
TI  - [Cholelithiasis--laparoscopy or laparotomy?].
AB  - Between 10% and 15% of the adult population have gallstones and therefore
      symptomatic cholelithiasis is the second most common indication for surgery in
      general practice. It's diagnosis depends on the patients history, clinical
      findings, laboratory tests and ultrasound. In case of symptomatic gallstones
      surgery offers the only permanent cure and specific complications due to
      gallstones such as ileus or fistula are becoming rare. With the introduction of
      minimal invasive surgery at the end of this century laparoscopic cholecystectomy
      is now considered to be the standard treatment for symptomatic gallstones. This
      approach can be offered to > 90% of patients in elective cases and in between 60%
      80% of patients having acute cholecystitis with a low morbidity and mortality
      rate. The main advantages of the laparoscopic approach are the overall increased
      patients comfort with less postoperative pain, shorter hospital stay, recovery
      and off work time. Although the rate of common bile duct injury appears to be
      increased using this minimal invasive approach, this rate is still sufficiently
      small to justify the use of laparoscopic cholecystectomy for symptomatic disease.
      Open cholecystecomy remains the treatment of choice for complicated gallstone
      disease (i.e. cancer, Mirizzi syndrome, severe inflammation) and high risk
      patients. In case of acute cholecystitis the laparoscopic treatment with all it's
      advantages may also be offered to many patients. However, in those cases the
      conversion rate to the open approach may be markedly increased which has not to
      be considered as a complication of the laparoscopic approach but as a
      maximization of safety and effectiveness of the treatment.

PMID- 9545854
TI  - [Treatment of choledocholithiasis].
AB  - Passage of gallstones into the common bile duct occurs in 10-15% of patients with
      cholecystolithiasis. The incidence of common bile duct stones increases with age
      of the patient and can reach up to 50% in certain series. The diagnosis of
      choledocholithiasis is usually made by endoscopic retrograde cholangiography
      (ERC), either preoperatively or intraoperatively at the time of laparoscopic
      cholecystectomy. Endoscopic sphincterotomy followed by balloon or basket
      extraction is the method of choice for the management of patients with common
      duct stones.

PMID- 9545855
TI  - [Differential diagnosis and therapy of benign liver tumors].
AB  - Hemangioma, focal nodular hyperplasia (FNH) and hepatocellular adenoma represent
      the most common and clinically relevant benign liver tumors. Improved diagnostic
      imaging procedures as well as the broad use of oral contraceptives resulted in an
      increased detection rate during the past 25 years. Focal liver diseases are
      primarily diagnosed by ultrasonography, while a specific diagnosis can be
      established by contrast enhanced magnetic resonance imaging. Hepatocellular
      adenomas should be resected, since they bear the potential of a malignant
      transformation as well as the risk of rupture and intraperitoneal hemorrhage.
      Conversely, a conservative approach is advocated for hemangioma and FNH. However,
      surgical procedures may be justified when a mass becomes symptomatic, and should
      be applied liberally when the diagnosis remains uncertain.

PMID- 9545856
TI  - [Diagnosis and treatment of hepatocellular carcinoma].
AB  - Worldwide, hepatocellular carcinoma is one of the most common intra-abdominal
      malignancy. It occurs mostly in patients who are carriers of the hepatitis B or C
      virus and/or have liver cirrhosis. There is no screening-test for early
      recognition of the development of liver cancer and this delays often an accurate
      diagnosis and early treatment. Resection is the best form of treatment offering a
      chance of cure. In the last decades, considerable progress has been made in the
      field of liver diagnostic and operative techniques for liver resection. This has
      been followed by an increase in the resection rate of patients with malignant
      liver tumours and by a decrease in postoperative morbidity and mortality.
      Nowadays, after curative resection, 5-year survival rates up to 30% can be
      achieved. Promising results are also obtained by new adjuvant therapeutic
      modalities demonstrating improvement in survival. Therefore, in the field of
      malignant liver tumours there is no more space for therapeutic nihilismus.

PMID- 9545857
TI  - [Indications and results of liver transplantation].
AB  - Liver transplantation offers cure and high a quality of life to patients with
      otherwise incurable diseases. For patients suffering from chronic liver diseases
      or metabolic disorders, a life expectancy of less than one year or an
      unacceptable quality of life are considered to be indications for
      transplantation. For unresectable primary liver tumors without vascular invasion
      or tumor manifestations outside the liver long-term survival can be achieved with
      transplantation. Because of the enormous regenerative capacity of the liver,
      indication for transplantation can be difficult in case of fulminant hepatic
      failure, for which own criteria have been defined. In relation to the under-lying
      liver disease one-year patient survival varies from 60%-80%. Recurrence of tumors
      or viral hepatitis may have a negative impact of long-term outcome. Various
      indications and results are discussed in detail.

PMID- 9545858
TI  - [Management of the liver transplant patient].
AB  - The general practitioner plays a crucial role in the care for the liver
      transplant recipient. The number of liver transplant recipients increasing
      steadily by about 50 a year in Switzerland, the practitioner will increasingly be
      confronted with such patients. A close cooperation between general practitioner
      and transplant center is mandatory and the key to success. This paper aims at
      introducing the general practitioner to the care for the liver transplant
      recipient.

PMID- 9545859
TI  - [Establishment of Sendai virus gene manipulation and its applications].

PMID- 9545860
TI  - [Structure/function analysis of rice dwarf phytoreovirus genome and its
      proteins].

PMID- 9545861
TI  - [Structure-function relationship of the influenza virus RNA polymerase].

PMID- 9545862
TI  - [NO in the pathogenesis of viral infections].

PMID- 9545863
TI  - [Viral ion channel: structure and function of influenza virus M2 protein].

PMID- 9545864
TI  - [Neuropathogenic murine retrovirus].

PMID- 9545865
TI  - [Current status of gene therapy and viral vectors].

PMID- 9545866
TI  - [Process development for large scale procreation of retroviral vectors].

PMID- 9545867
TI  - [Gene transfer into non-dividing cells by a lentiviral vector].

PMID- 9545868
TI  - [Adeno-associated virus vectors and gene therapy].

PMID- 9545869
TI  - [Next generations of adenovirus vector: present and future].

PMID- 9545870
TI  - [Herpes simplex virus as a vector for gene therapy].

PMID- 9545871
TI  - [Gene transfer into mammalian cells by baculovirus vector and its applications].

PMID- 9545872
TI  - [Glycoprotein C of herpes simplex virus].

PMID- 9545873
TI  - [Hemagglutinating virus of Japan].

PMID- 9545874
TI  - Phenolic constituents of licorice (Glycyrrhiza species).

PMID- 9545875
TI  - Antibacterial effect of propolis and honey on oral bacteria.
AB  - PURPOSE: To investigate the antibacterial properties of propolis and honey
      against oral bacteria in vitro and in vivo. MATERIALS AND METHODS: In vitro
      study: The antibacterial effects of propolis and honey on oral streptococci were
      determined using the broth method. Clinical study: The short-term antibacterial
      effect of propolis solution and honey on salivary total bacteria and
      Streptococcus mutans was tested in 10 volunteers. RESULTS: Propolis demonstrated
      an antibacterial effect both in vitro on isolated oral streptococci and in the
      clinical study on salivary bacterial counts. Honey induced bacteria growth at low
      concentrations, while at high concentrations honey had an inhibitory effect on
      bacterial growth in vitro. Salivary counts of total bacteria and Streptococcus
      mutans were lower for 1 hour after application of honey. The antibacterial effect
      of the honey tested may be attributed to its osmolarity effect.

PMID- 9545876
TI  - Dentin infiltration by three adhesive systems in clinical and laboratory
      conditions.
AB  - PURPOSE: To evaluate in vivo and in vitro the formation of hybrid layer, resin
      tags and adhesive lateral branches, by use of three different enamel dentin
      bonding systems. MATERIALS AND METHODS: The dentin adhesives were tested on flat
      dentin preparations made on buccal surfaces of vital, periodontally compromised
      teeth. The samples were randomly divided in four groups: Group 1: Prime & Bond
      2.0; Group 2: Scotchbond Multi-Purpose Plus; Group 3: Clearfil Liner Bond 2 (the
      self-etching primer was applied for 30 seconds on the enamel and dentin); Group
      4: Clearfil Liner Bond 2 (the self-etching primer was applied for 60 seconds on
      the enamel and dentin). The sample teeth were extracted immediately after the
      bonding was cured. The same procedure described for the in vivo samples was
      performed in vitro on extracted molars. All the samples were split-fractured
      along their long axis. Half of the samples were used to visualize the hybrid
      layer and the other half to observe the morphology of resin tags by use of
      scanning electron microscopy. RESULTS: All the tested products formed a hybrid
      layer, both in vivo and in vitro. In many areas of the samples of Groups 1, 2 and
      4, characteristic reverse cone-shaped tags with their corresponding adhesive
      lateral branches were evident. In contrast to this, resin tags found in samples
      of Group 3 were narrower at the tubule orifices, and adhesive lateral branches
      were scarce. The length of the resin tags observed in the samples of Groups 1 and
      2 were longer than those found in Groups 3 and 4. The morphology of the hybrid
      layer of the in vivo samples was similar to that of the in vitro samples.

PMID- 9545877
TI  - Microleakage of multi-step and simplified-step bonding systems.
AB  - PURPOSE: To measure and compare the microleakage of Class V resin composite
      restorations using the following three pairs of multi- and simplified-step dentin
      bonding systems (DBS): OptiBond vs. OptiBond FL, All-Bond 2 vs. One-Step, and
      Tenure vs. Tenure Quik. MATERIALS AND METHODS: V-shaped cavities were prepared in
      the mesial and distal surfaces of 30 extracted human mandibular molars with
      margins in both enamel and cementum, and randomly assigned into three equal
      groups of 10 each. All DBSs were applied strictly following manufacturers'
      specifications before three incremental layers of resin composite (Pertac-Hybrid)
      were applied in all cavities. Specimens were stored for 7 days in 37 degrees C
      water, thermocycled for 300 cycles between 5 degrees C and 55 degrees C, immersed
      in 0.5% basic fuchsin solution for 24 hours, and embedded in resin before being
      sectioned longitudinally in multiple sections. Dye solution penetration at the
      tooth/composite interface was scored from 0 to 4 under a microscope at x100 at
      both enamel (E) and cementum (C) margins. Data were analyzed by Kruskal-Wallis
      and Mann-Whitney U tests with alpha = 0.05. RESULTS: OptiBond FL and One-Step
      showed less microleakage at the cementum margins compared to their multi-step
      versions. At the enamel margins Tenure Quik showed less microleakage compared to
      Tenure, and none of the other DBSs tested showed significant dye penetration at
      that interface. All DBSs showed significantly less microleakage at the enamel
      margins compared to the cementum margins except for OptiBond FL and One-Step that
      did not show any significant dye penetration at the cementum margins as well.

PMID- 9545878
TI  - Microleakage of dentin bonding systems used with spherical and admixed amalgams.
AB  - PURPOSE: To evaluate the effectiveness of the dentin bonding systems (DBS)
      Tenure, Syntac, Amalgambond and All-Bond 2 using a resin-lined amalgam technique
      in preventing short-term microleakage in Class V cavity preparations restored
      with a spherical and an admixed alloy. MATERIALS AND METHODS: Class V cavity
      preparations were made on the mesial and distal surfaces of non-carious human
      mandibular molars with the occlusal margins in enamel and gingival margins in
      cementum. Prepared teeth were randomly assigned to 12 treatment groups (n = 10)
      consisting of each DBS, no liner and Copalite for both amalgam alloys. Samples
      were thermocycled, stained and sectioned to evaluate microleakage. RESULTS: The
      DBS-lined restorations had significantly less microleakage at both occlusal and
      gingival margins than the Copalite and unlined restorations. Among DBS, Syntac
      had significantly more microleakage with both alloys than either All-Bond 2 or
      Amalgambond. These results do not totally correlate to a previous study which
      used the same experimental design but included viscous liners in addition to the
      same DBS, indicating a potential difference between resin-lined versus resin
      bonded amalgam techniques in preventing microleakage.

PMID- 9545879
TI  - Marginal adaptation of resin-bonded light-cured glass ionomers in dentin
      cavities.
AB  - PURPOSE: To investigate the marginal adaptation of resin-modified glass ionomer
      cements in dentin cavities placed with or without additional application of resin
      bonding systems. MATERIALS AND METHODS: Three resin-modified materials (Fuji II
      LC, Photac-Fil, Vitremer), one compomer (Dyract) and as reference an adhesively
      bonded resin composite system (Gluma CPS-Pekafill) were used. Flat peripheral
      dentin surfaces on human molar teeth were produced by wet grinding on SiC paper.
      Cylindrical cavities, 3.5 mm wide, were prepared in these dentin areas and
      restored with the individual materials. Sixty cavities were pretreated and
      restored as requested by the respective manufacturers. Following water storage of
      the specimens for 15 minutes or 24 hours, excess was gently removed by wet
      grinding for microscopic inspection of the marginal area. Additionally, in 30
      cavities an experimental one-component adhesive resin system, a proprietary
      dimethacrylate and HEMA mixture dissolved in acetone, was combined with each of
      the restoratives for evaluation after 15-minutes water storage. Finally, in six
      cavities each, Dyract was combined with Prime and Bond 2.0, and Vitremer with
      Scotchbond Multi-Purpose Plus for assessment after 15 minutes. Maximum marginal
      gap widths (MGW) were measured. One-way ANOVA by ranks (Kruskal-Wallis-Test)
      followed by Wilcoxon's Two-Sample test were used to study the statistical
      difference of MGW among the treatment groups at a rejection level P = 0.05.
      RESULTS: Neither the conventionally placed material systems nor the restorations
      in combination with adhesives showed consistently gap-free margins after 15
      minute water storage. After 24-hour storage with Vitremer 4 of the 6 restorations
      were gap-free, whereas with all other materials only perfect margins were
      registered. There was, however, no significant difference between the groups.
      Application of the experimental and/or the specific resin bonding agents had no
      effect on early MGW except for the Photac-Fil group, which was significantly
      reduced.

PMID- 9545880
TI  - Compomers and glass ionomers: bond strength to dentin and mechanical properties.
AB  - PURPOSE: To compare compomers and conventional and resin-modified glass ionomer
      cements (GIC) with respect to bond strength to dentin and mechanical properties.
      MATERIALS AND METHODS: Seven conventional GICs (BaseLine, ChemFil Superior, Fuji
      II, Fuji IX, Ketac-Fil, Ketac-Silver, and Miracle Mix), three resin-modified GICs
      (Fuji II LC, Photac-Fil, and Vitremer), and two compomers (Dyract and Compoglass)
      were investigated. Bond strength was determined to untreated as well as pre
      treated human dentin. The mechanical properties tested were flexural strength and
      flexural modulus. RESULTS: Mean bond strengths to untreated dentin ranged from
      0.0 MPa (Photac-Fil) to 8.5 MPa (Fuji IX). Generally, the bond strengths of the
      compomers and resin-modified GICs were lower than those of the conventional GICs.
      Mean bond strengths to pre-treated dentin ranged from 0.5 MPa (Photac-Fil) to
      13.7 MPa (Compoglass). No clear-cut bond strength pattern was observed for the
      three types of materials. Pretreatment improved the bond strength of nine out of
      12 materials. Flexural strengths ranged from 13 MPa (Miracle Mix) to 180 MPa
      (Dyract). Generally, the compomers were stronger than the resin-modified GICs,
      which were much stronger than the conventional GICs. Flexural moduli ranged from
      4.0 GPa (Miracle Mix) to 7.2 GPa (Fuji IX and Dyract) with no typical variations
      between the three categories of materials.

PMID- 9545881
TI  - Effect of polymerization mode of a dual-cured resin cement on time-dependent
      shear bond strength to porcelain.
AB  - PURPOSE: To evaluate the shear bond strengths to porcelain and setting times of a
      dual-cured resin cement with light/chemical curing (dual) or chemical only curing
      versus time. MATERIALS AND METHODS: Variolink resin cement was bonded to
      specimens of etched, silanated porcelain. Groups of specimens were cured by dual
      cured or by chemical curing only. Shear bond strengths were recorded at 2, 3, 5,
      60 minutes and 24 hours for dual cured and at 10, 20, 40, 50, 60 minutes and 24
      hours for chemical-cured only after mixing. Kinetic-temperature profiles of dual
      and chemical curing modes of cement were calculated. RESULTS: Maximum bond
      strengths and time to attainment were 17.5 +/- 2.7 MPa at 60 minutes for chemical
      cured and 26.1 +/- 2.3 MPa at 5 minutes for dual-cured. The peak in the kinetic
      temperature setting profiles were 14.1 +/- 0.9 minutes for chemical curing and
      52.2 +/- 5.2 seconds for dual curing. Dual curing provided significantly higher
      shear bond strengths versus chemical curing at both the 60-minute and 24-hour
      time periods.

PMID- 9545882
TI  - Bond strength of multi-step and simplified-step systems.
AB  - PURPOSE: To measure and compare the in vitro shear bond strength (SBS) of the
      following three pairs of multi- and simplified-step dentin bonding systems:
      OptiBond vs. OptiBond FL, All-Bond 2 vs. One-Step, and Tenure vs. Tenure Quik.
      MATERIALS AND METHODS: 60 extracted human mandibular molars were sectioned
      perpendicular to the long axis 1 mm above the CEJ to expose the dentin bonding
      surface. After being wet-ground to 600 grit with SiC abrasive papers, rinsed and
      dried, the teeth were individually mounted in phenolic rings with epoxy resin,
      and randomly assigned into six equal groups of 10 each. The dentin surfaces were
      treated with the above mentioned dentin bonding systems, and a gelatin cylinder
      filled with resin composite (Pertac-Hybrid) was directly bonded to each
      pretreated surface. After 7-day storage in 37 degrees C water followed by
      thermocycling, the specimens were shear tested to failure on an Instron machine.
      Data were analyzed by independent t-tests, one-way ANOVA, and Duncan's Multiple
      Comparison tests at alpha = 0.05. RESULTS: Except for the pair Tenure/Tenure
      Quik, the differences between the pairs All-Bond 2/One-Step and OptiBond/OptiBond
      FL were statistically significant with All-Bond 2 and OptiBond FL yielding higher
      shear bond strength (P < 0.05). Findings of this study indicated that OptiBond FL
      was the only simplified-step system showing improved bond strength.

PMID- 9545883
TI  - Wet bonding: effect of drying time and distance.
AB  - PURPOSE: To examine the effect of various drying times and air syringe-to-tooth
      distances on the shear bond strength of a dentin adhesive that requires a wet
      surface for maximum effectiveness. MATERIALS AND METHODS: Seventy extracted human
      molars were acid etched. The surface of the etched dentin was rinsed and dried
      with compressed air for 1, 3, or 5 seconds from a distance from either a distance
      of 1 or 10 cm. The adhesive One-Step was then applied, composite cylinders were
      attached and shear bond strengths were obtained. RESULTS: Drying time and
      distance had a significant impact on the resultant shear bond strengths. Longer
      drying times and shorter syringe-to-tooth distances negatively affected the bond
      strength of the adhesive studied.

PMID- 9545884
TI  - 2-year clinical performance of a fluoride-containing fissure sealant in young
      schoolchildren at caries risk.
AB  - PURPOSE: To evaluate the clinical performance of Helioseal-F, a fluoride
      containing fissure sealant, in school children at caries risk. MATERIALS AND
      METHODS: A caries risk assessment based on past caries experience, saliva
      microbial tests, buffer capacity and frequency of sugar intake was carried out in
      204 healthy children, 6-7 years of age. Children exhibiting one or more risk
      factors were considered at caries risk (n = 121) and their permanent molars were
      sealed with a fluoride-containing fissure sealant, thus forming a fissure sealant
      group (FSG). The remaining 83 children with low caries risk received no fissure
      sealants and constituted a reference group (RG). Both groups were followed for 2
      years. From 15 children of both groups, unstimulated whole saliva was collected 1
      month after sealant placement in order to determine fluoride levels. In another
      20 children, a split-mouth study design was utilized to compare the colonization
      of mutans streptococci adjacent to and on F-containing sealants and conventional
      controls. The sealants were placed by dental hygienists according to the
      manufacturers' instructions. RESULTS: A total of 431 fissure sealants were placed
      at baseline. Complete retention was found in 76.6% during the study period while
      22.0% were partially lost. Six sealants (1.4%) were completely lost. The enamel
      caries incidence was 45% lower (P < 0.05) in the permanent molars of the caries
      risk FSG compared with the low risk RG. There was no significant increase in
      saliva fluoride concentration following placement of the sealants and the
      proportion of mutans streptococci in relation to total viable counts was
      unaffected by type of material. The levels of salivary mutans streptococci were
      mainly unchanged in both groups during the study period, while the levels of
      salivary lactobacilli decreased in the FSG.

PMID- 9545885
TI  - Manipulation effects on fluoride release from chemically-cured and resin-modified
      glass ionomers.
AB  - PURPOSE: To examine the effect of mixing techniques (hand-mixing vs. trituration)
      on fluoride release from chemically-cured (Fuji II) and resin-modified (Fuji II
      LC) glass ionomer products. MATERIALS AND METHODS: Fluoride measurements were
      determined and comparisons made between hand-mixed-type materials that were both
      hand-mixed (60 seconds) and triturated (10 seconds). Hand-mixed specimens were
      made using the manufacturer's recommended powder/liquid ratio. Triturated
      specimens of the same material were made using the same powder/liquid ratio. Disk
      specimens (8.5 mm diameter, 2 mm thickness; n = 6) were stored in deionized water
      for 23 hours to obtain Day 1 solutions. Solutions were also obtained at 2, 3, 4,
      5, 6, 7, 14, 21, and 28 days after fabrication and were changed 24 hours before
      fluoride concentration was determined using a fluoride ion selective electrode.
      Daily rates of fluoride release and 28-day cumulative fluoride totals were
      calculated. Cumulative data were analyzed by two-way ANOVA and Scheffe's test
      (alpha = 0.05). Daily results were analyzed by the Mann-Whitney U-test. RESULTS:
      A significant difference was observed between materials (P < 0.001). Depending on
      the kind of material used, the method of manipulation affected the fluoride
      release. Data analysis revealed that: (1) Fuji II LC released significantly more
      fluoride than Fuji II for both triturated (P = 0.005) and hand-mixed (P < 0.005);
      (2) the triturated Fuji II released significantly more fluoride than the hand
      mixed (P = 0.02); and (3) the hand-mixed Fuji II LC released more fluoride than
      the triturated, but was not statistically significant (P = 0.16).

PMID- 9545886
TI  - VariGlass fluoride release and uptake by an adjacent tooth.
AB  - PURPOSE: To quantitatively analyze in vitro the fluoride release from proximal
      VariGlass restorations and resulting uptake by the enamel of adjacent teeth.
      MATERIALS AND METHODS: Sixty impacted third molars were used and assigned to
      three groups: C: control, teeth without restorations; RC: teeth with resin
      composite restorations (Prisma APH); and PMRC: teeth with polyacid-modified resin
      composite restorations (VariGlass). Each group consisted of four sets of five
      teeth each. In the latter two sets, by alternating restored and unrestored teeth,
      the proximal surfaces of three unrestored teeth with an area of exposed enamel
      were in contact with the restored proximal surfaces of two other teeth. The sets
      were submitted to high caries challenge conditions with demineralizing and
      remineralizing solutions for 14 days. The fluoride of each solution and the
      fluoride uptake were determined and statistical analyses were carried out (ANOVA
      and Tukey's test). RESULTS: The highest mean fluoride concentration occurred with
      Group PMRC in both kinds of solutions (P < 0.01), but this value was higher in
      the demineralizing solution (P < 0.01). Over the 14 days, however, this mean
      gradually decreased in both solutions (P < 0.01). Group PMRC also showed the
      highest mean fluoride uptake (P < 0.01), which gradually decreased with depth in
      the enamel (P < 0.01).

PMID- 9545887
TI  - Bond strength and interface micromorphology of an improved resin-modified glass
      ionomer cement.
AB  - PURPOSE: To evaluate the influence of surface treatment with 20% polyacrylic acid
      containing 3% aluminum chloride (AlCl3) on the shear bond strength of an improved
      resin-modified glass ionomer cement to enamel and dentin, and to analyze the
      micromorphology of the cement-tooth interface. MATERIALS AND METHODS: Flat enamel
      and dentin surfaces of bovine incisors were ground up with sequentially finer
      abrasives to 1000-grit silicon carbide paper. Each surface was treated with 10%
      polyacrylic acid (Dentin Conditioner: DC) for 20 seconds or with 20% polyacrylic
      acid containing 3% aluminum chloride (Cavity Conditioner: CC) for 10 seconds,
      rinsed, and gently air-dried. A resin-modified glass ionomer cement (Fuji II LC)
      and its improved version (Fuji II LC-I) were applied to the tooth substrate, and
      bond strengths measured at periods of 5 minutes, 1 day, and 1 week after light
      curing. As a control, the resin-modified glass ionomer cements were applied to
      untreated surfaces and were tested at 1 day. To evaluate the interface
      micromorphology, specimens were prepared following the adhesive-sandwich
      technique, cut in equal halves, and observed under a scanning electron microscope
      (SEM). Additionally, in order to observe the effect of surface pre-treatment of
      each conditioner on dentin, pre-treated dentin disks were freeze-dried,
      fractured, and the morphology of the treated and fractured surfaces were
      observed. RESULTS: Shear bond strength of CC+ Fuji II LC-I to enamel was
      significantly higher than that of DC+ Fuji II LC at 1 day and 1 week (P <
      0.0001). As for dentin, the improved system showed significantly higher bond
      strength at 5 minutes after light curing (P < 0.001), but bond strengths were not
      statistically different at 1 day and 1 week. Fracture patterns, examined with a
      stereomicroscope, were mixed adhesive/cohesive within the cement for all groups.
      Interface micromorphology, observed with an SEM, suggested the formation of a
      resin-rich layer and an indistinct zone between the resin-modified glass ionomer
      cements and the underlying dentin.

PMID- 9545888
TI  - Changes to Dyract restorative resin immersed in various media.
AB  - PURPOSE: To examine changes in weight, strength, fluoride release, and surface
      changes to the polyacid-modified resin composite Dyract after immersion in
      various media for periods up to 16 weeks. MATERIALS AND METHODS: Properties
      investigated were change in weight, strength, release of fluoride ions, and
      surface changes. Specimens were immersed in reverse osmosis deionized water (ROW)
      and in acetate buffer solutions containing calcium hydrogen orthophosphate. The
      acetate media were of pH3, pH5 and pH7. All solutions were maintained at 37
      degrees C without agitation. Solutions were changed weekly and retained for
      fluoride analysis and specimens were weighed each week. After periods of 1, 2, 3,
      4, 8, 12 and 16 weeks, some specimens were subjected to shear punch testing and
      SEM examination. RESULTS: All specimens except those in pH3 medium gained weight
      for the first 2-5 weeks after which weight was lost until all specimens weighed
      less than at the commencement of the study. The specimens in pH3 medium lost
      considerable weight from weeks 1 and 2. SEM examination showed disintegration of
      the surface of all specimens examined. Fluoride release peaked at 1 week in all
      specimens except those in pH3 medium. Fluoride release was highest in pH3 media
      (approximately 46 ppm) after 1 week and remained high for 7 weeks, after which it
      was reduced to about 50% of the initial release. Specimens stored in ROW and pH5
      media released approximately 5 ppm after 1 week, and this was reduced to
      approximately 1 ppm (pH7) and 2 ppm (ROW) by week 6.

PMID- 9545889
TI  - Surface finishing of glass ionomer.
AB  - PURPOSE: To evaluate the surface roughness and staining of a glass ionomer cement
      when subjected to different finishing procedures. MATERIALS AND METHODS: Sixty
      four discs of Chem-Fil II glass ionomer cement were submitted to staining test
      with methylene blue by spectrophotometry and roughness test by profilometry. Four
      groups were evaluated: Mylar matrix (control). Sof-Lex discs, Enhance points, and
      diamond bur. RESULTS: Staining and roughness test, analyzed by ANOVA and Tukey's
      test, showed that the best surface was obtained when the material cured in
      contact with the Mylar matrix strip or when treated with Sof-Lex discs. The
      poorest results were obtained after using the diamond bur.

PMID- 9545890
TI  - Laboratory evaluation of compomers in Class V restorations.
AB  - PURPOSE: To evaluate the in vitro microleakage, marginal morphology and resin
      tags configuration of a compomer restorative material (Dyract) alternatively used
      with two different bonding systems (Dyract-PSA and Prime & Bond 2.0). A hybrid
      resin composite (Prisma TPH) used with two different bonding systems (Universal
      Bond 3 and ProBond) was evaluated as control material. MATERIALS AND METHODS:
      Class V non-retentive restorations were made in vitro at CEJ and divided at
      random in four groups: Dyract/PSA, Dyract/P&B 2.0, Prisma TPH/UB3, and Prisma
      TPH/ProBond. The latter two groups were as controls. After finishing the
      restorations, an impression material was used to obtain an epoxy resin replica
      for SEM analysis of margin alterations. Percentage of perfect margin was
      evaluated under SEM and calculated comparing it with the width/length of
      restoration margin. The presence of gaps, enamel fractures and other marginal
      alterations was also recorded inspecting under SEM replicas. Each tooth was then
      immersed for 24 hours in erythrosin B dye solution at room temperature and
      evaluated at superficial margins as marginal leakage (ML) for dye penetration.
      Each sample was then longitudinally sectioned, and leakage was expressed as % dye
      penetration of the total cavity wall, longitudinal leakage (LL). Finally, each
      tooth was dissolved (10%H3PO4 for 48 hours and NaOCl solution for additional 24
      hours) to leave only the resin restoration. The internal walls of each
      restoration were then inspected by SEM at x1,000-15,000 to evaluate the presence
      of resin-dentin infiltrated layer (hybrid layer) and to calculate the ability of
      primer/bonding to infiltrate peritubular dentin and to form resin tags. RESULTS:
      Gap widths were 2-6 microns at dentin and lower at enamel. Several enamel
      fractures along the margin were observed. Resin tags were observed only in deeper
      dentin. Only Prime & Bond 2.0/Dyract formed resin tags at medium-superficial
      dentin. The length of resin tags ranged from 1-6 microns for Dyract-PSA primer to
      100 microns for Prime & Bond 2.0. Marginal and longitudinal leakage was observed
      both at dentin and enamel levels. The best dentin seal was obtained with Prime &
      Bond 2.0/Dyract, while enamel seals were equivalent with both bonding systems (P
      > 0.05). No correlations were demonstrated between leakage and SEM observations.

PMID- 9545891
TI  - Effect of HEMA-containing dentin desensitizers on shear bond strength of a resin
      cement.
AB  - PURPOSE: To determine whether the use of two HEMA-containing dentin desensitizing
      agents [Health-Dent Desensitizer with fluoride (H) or Gluma Desensitizer (G)],
      when applied at simulated "cavity preparation" and "cementation" appointments,
      affects the bond strength of lab processed resin composite restorations cemented
      to dentin. MATERIALS AND METHODS: The occlusal surfaces of 70 teeth were ground
      flat to expose dentin and polished to 600 grit. Teeth were randomly assigned to
      seven groups (n = 10). The treatments were applied in two sessions in order to
      simulate cavity preparation and cementation appointments. Water (W) was applied
      as a control instead of a desensitizing agent. H or G were applied for 30 seconds
      with a rubbing motion (1) at preparation appointment (HW and GW), or (2) at
      cementation appointment, after etching (WH and WG), or (3) at both sessions (HH
      and GG). In the control group, water was applied at both sessions (WW). All-Bond
      2 and Dual Cement were used according to manufacturers' instructions to cement
      pre-polymerized resin composite cylinders (4 mm diameter) to the dentin surfaces
      using a force of 1.0 MPa. Specimens were thermocycled 300x and tested in shear
      until failure. Data was analyzed using one-way ANOVA and Tukey's HSD test at
      alpha = 0.05. RESULTS: Mean bond strength and standard deviations are reported in
      MPa: GW = 7.4 +/- 6.0; WW = 7.7 +/- 5.8; HW = 8.2 +/- 4.3; WH = 10.8 +/- 6.2; GG
      = 13.5 +/- 6.0; HH = 13.8 +/- 7.1; WG = 19.9 +/- 8.8. There were no significant
      differences in bond strengths for GW, WW, HW, WH and GG. Shear bond strength for
      WG and HH was significantly higher than all groups except for GG. Results of this
      in vitro study indicate that the use of desensitizers at the preparation and/or
      cementation appointment does not interfere with bond strengths of resin cement to
      dentin.

PMID- 9545892
TI  - Effect of two etching times on the sealing ability of Clearfil Liner Bond 2 in
      Class V restorations.
AB  - PURPOSE: To investigate the sealing ability of the Clearfil Liner Bond 2 self
      etching primer in Class V restorations placed under clinical and laboratory
      conditions. MATERIALS AND METHODS: Firstly, the influence of two etching times of
      the self-etching primer were tested in vitro. In 10 Class V cavities (Group 1),
      the self-etching primer was applied for 30 seconds on the enamel and dentin,
      while in another 10 Class V cavities (Group 2) the etching time was 60 seconds.
      Since the Group 2 samples showed the best in vitro sealing ability at both the
      enamel and cementum-dentin sites, the teeth of Group 3 (10 restorations) were
      restored as in Group 2 under clinical conditions, applying the self-etching
      primer for 60 seconds. The sample teeth were extracted after 65-90 days, and then
      processed for leakage. Two other groups of 10 samples each were prepared under
      laboratory conditions to investigate hybrid layer, resin tags and adhesive
      lateral branch formation. A flat buccal surface on each extracted tooth was
      prepared. Group 4 samples were conditioned for 30 seconds, and those of Group 5
      for 60 seconds. RESULTS: In Group 1, 40% of the restorations showed leakage at
      the cementum-dentin site and 40% at the enamel site. Groups 2 and 3 showed
      statistically significant difference (less leakage) than Group 1. In Group 2 and
      3 no leakage was found at the enamel site, and only a moderate leakage (10% and
      20% of restorations, respectively) was found at the cementum-dentin site. The
      scanning electron microscopy observations of Group 4 samples showed a thin hybrid
      layer, with well-fitting and smooth resin tags and adhesive lateral branches only
      sporadically. Group 5 samples presented a thicker hybrid layer, rough and deep
      resin tags with many adhesive lateral branches. The etch enamel pattern was more
      uniform and rougher in Group 5 than in Group 4. The 60-second application time of
      the self-etching primer seems to be more reliable than a shorter conditioning
      time in day-to-day practice.

PMID- 9545893
TI  - Bond strength of one-bottle dentin bonding agents on human dentin.
AB  - PURPOSE: To evaluate the shear bond strength of one-bottle dentin bonding agents
      (DBA's) (Prime & Bond 2.1, ART Experimental, Syntac Single Component) on
      pressurized human dentin. MATERIALS AND METHODS: Freshly prepared dentin
      specimens of human teeth were perfused with horse serum which was diluted 1:5 in
      physiologic saline. Three different types of surface treatment were evaluated on
      the freshly prepared dentin. Group 1: One of the three one-bottle DBA's was
      applied onto freshly prepared dentin together with a cylinder of composite luting
      resin and cured. Group 2: A provisional cement (Freegenol, without eugenol, or
      Temp Bond, containing eugenol) was applied first on the dentin surface for 24 h.
      Only then was one of the three the one-bottle DBA's added onto the dentin
      together with a cylinder of composite luting resin after cleaning the dentin
      surface with pumice. Group 3: One of the three one-bottle DBA's was applied first
      on the dentin surface and light-cured. Then a provisional cement (Freegenol,
      without eugenol, or Temp Bond, containing eugenol) was added for 24 h. After
      cleaning with pumice, the respective one-bottle DBA was applied for a second time
      onto the dentin together with a cylinder of composite luting resin and light
      cured. As control for Group 1 (freshly prepared dentin), the two- or three-step
      DBA's ART Bond and Syntac were used in a similar way. As control for Group 2
      (single application of the DBA's after contamination of the dentin with a
      provisional cement) and Group 3 (dual application of the DBA's with intermediate
      contamination of the dentin with a provisional cement) the two-step DBA ART Bond
      was used. After 1500 thermal cycles with constant imitation of intrapulpal
      pressure, shear bond strengths were measured. Resulting shear bond strength
      values were displayed by means of a box plot and they were analyzed statistically
      by Student's t-Test or one-way ANOVA. RESULTS: Lowest and highest mean shear bond
      strength values were 0.26 +/- 0.47 MPa (single use of ART Bond with prior
      application of Temp Bond) and 16.34 +/- 5.02 MPa (dual use of ART Bond with
      intermediate application of Temp Bond). With respect to the surface treatment
      significant differences between the DBA's could be found in all groups.

PMID- 9545894
TI  - Ultrastructure of the resin-dentin interface following reversible and
      irreversible rewetting.
AB  - PURPOSE: This study investigated the effect of reversible and irreversible
      rewetting on the application of One-Step, single-bottle, water-free, acetone
      based primer/adhesive. MATERIALS AND METHODS: Thirty 1 mm dentin discs prepared
      from third molars were each conditioned with 10% H3PO4 for 20 seconds and rinsed
      for 20 seconds. They were randomly divided into five groups: Group 1 (positive
      control): conditioned dentin bonded visibly moist; Group 2: bonded after drying
      for 3 seconds; Group 3: drying for 3 seconds and rewetting with distilled water;
      Group 4 (negative control): drying for 3 seconds, stored in 8% glutaraldehyde for
      15 minutes, rinsed with distilled water and dried for 3 seconds; and Group 5:
      drying for 3 seconds, stored in glutaraldehyde for 15 minutes, rinsed with
      distilled water and bonded visibly moist. One-Step was applied in two coats
      according to the manufacturer's recommendation and discs in each group were
      further bonded together to form a disc-pair using a chemical cure resin,
      demineralized in EDTA and prepared for TEM examination. RESULTS: Complete resin
      infiltration into the zone of demineralized dentin was observed in Group 1 and 3.
      In Group 2, resin infiltration was limited to the surface and base of the
      demineralized network apparently along the lateral branches of the dentin
      tubules. A middle zone of suboptimal infiltration was observed. In Group 4 and 5,
      minimal resin infiltration was only observed along the base of the demineralized
      network upon their fixation in a collapsed state with glutaraldehyde.

PMID- 9545895
TI  - Saliva contamination and bond strength of single-bottle adhesives to enamel and
      dentin.
AB  - PURPOSE: To determine and compare the shear bond strength of four single-bottle
      adhesives to enamel and dentin contaminated with human saliva. MATERIALS AND
      METHODS: Prime & Bond 2.1, One Step, Tenure Quik and Syntac Single Component were
      evaluated. Ninety-six sound molars were divided into three subgroups for each of
      the four adhesives. Small flat areas on the buccal and lingual surfaces were
      ground in enamel. Small flat areas on the mesial and distal surfaces were ground
      on the middle dentin of the same teeth. Each adhesive was tested under:
      uncontaminated conditions (Group 1), contamination of the bonding surface with
      fresh whole saliva for 20 seconds and removing the excess with cotton pellets
      (Group 2), and contamination of the bonding surface with fresh whole saliva for
      20 seconds and rinsing the saliva for 20 seconds before adhesive application
      (Group 3). After adhesive application, a plastic mold was filled with composite,
      applied to the bonding surface and light-cured. The teeth were thermocycled
      (1,000 cycles) and sheared using an Instron testing machine. The results were
      analyzed using a three-way ANOVA. RESULTS: Saliva contamination of enamel or
      dentin did not affect the shear bond strength of the adhesives tested except for
      Syntac SC with contaminated dried enamel. One Step displayed similar bond
      strengths to both enamel and dentin; P & B 2.1, Tenure Q and Syntac SC displayed
      higher bond strength to enamel than to dentin. P & B 2.1 showed significantly
      higher bond strengths to enamel than the other adhesives, but there was no
      significant difference for dentin bond strength under the uncontaminated
      condition.

PMID- 9545896
TI  - Effect of composite type, light intensity, configuration factor and laser
      polymerization on polymerization contraction forces.
AB  - PURPOSE: To investigate the effect of composite type, light intensity,
      configuration factor and laser polymerization on polymerization contraction
      force. MATERIALS AND METHODS: Glass rods (10 pairs/group) were etched with HF
      acid, silanated, unfilled resin applied and light cured for 20 s. Rods were held
      vertically in chucks on a Zwick machine. A cylindrical matrix was filled with
      Silar chemical cure, Silux Plus microfill or Z-100 hybrid composite and the
      crosshead of the UTM positioned at an inter-rod distance corresponding to a
      specific ratio of bound to unbound composite surface area (configuration factor
      or C). Exposure time with the Demetron 401 conventional visible light curing unit
      (D401) was 40 s/side (80 s total). Exposure times for the ILT Model D5500 air
      cooled laser (LAC) and Model 5500ABL water cooled laser (LWC) was 20 s/side (40 s
      total). Experimental groups, n = 10 with constant factors in parentheses,
      included: (1) Silar chemical-cured (C = 3); (2) Z-100 hybrid (C = 3, D401, 100%
      intensity); (3) Silux Plus microfill (C = 3, D401, 100% intensity); (4) D401 100%
      light intensity = 476 mW (Z-100, C = 3, D401); (5) D401 50% intensity = 238 mW (Z
      100, C = 3, D401); (6) D401 25% intensity = 119 mW (Z-100, C = 3, D401); (7-9) C
      = 5, 3 & 1 respectively (Z-100, D401, 100% intensity); (10) D401 with 13 mm tip =
      391 mW/cm2 (Z-100, C = 3; D401); (11) D401 with Turbo Tip = 811 mW/cm2 (Z-100, C
      = 3; D401); (12) LAC = 265 mW, 689 mW/cm2 (Z-100, C = 3); (13) LWC = 365 mW, 1100
      mW/cm2 (Z-100, C = 3). One Way ANOVA and Duncan's Multiple Range Test (alpha =
      0.05) were performed separately for each variable. RESULTS: Homogeneous subsets
      by variable were: composite type Group 1 (25N) < Group 3 (65.8N) < Group 2
      (90.4N); intensity Group 6 (73.9N) = Group 5 (77.7N) < Group 4 (90.4N); C-Factor
      Group 7 (81.8N) < Group 8 (90.4N) < Group 9 (103.4N); light source Group 12
      (77.4N) = Group 13 (79.1N) < Group 10 (90.4N) = Group 11.(89.4N). The chemical
      cured composite had the lowest maximum polymerization contraction force, the
      microfill was intermediate and the hybrid composite had the highest recorded
      force. Increases in light intensity increased the maximum force on the force/time
      curve. Maximum forces were inversely related to C-factor (C5 < C3 < C1) and
      directly related to composite volume in a non-rigid system which allowed
      compliance. Maximum force was not significantly different with the two tips
      tested on the conventional curing light. Forces obtained with laser
      polymerization were similar for the two laser groups, which were both
      statistically lower than the conventional light tested.

PMID- 9545897
TI  - Cavosurface margin geometry in conventional and air abrasion Class V cavity
      preparations.
AB  - PURPOSE: To compare cavosurface angle and area of missing tooth structure at the
      cavosurface margin in cross-sections of Class V cavity preparations made with a
      conventional carbide bur and with an air abrasive cavity preparation system.
      MATERIALS AND METHODS: Class V cavity preparations were made with a #56 carbide
      bur or with a KCP 1000 air abrasive unit. They were restored and sectioned
      longitudinally, providing 43 margins for study. Cavo-surface angle and area of
      missing tooth structure were measured for each margin from digital images of the
      sections. The angle and area data was grouped according to margin location and
      cavity preparation system and analyzed for differences using the Kruskal-Wallis
      test. To determine if there was a relationship between the missing area and the
      angle at the cavosurface margin, Lomb periodograms were analyzed. RESULTS:
      Conventional cavity preparation margins had an average cavosurface angle less
      than 90 degrees while the air abrasion margin angle was greater than 90 degrees.
      Cavo-surface angles for conventional cavity preparations were significantly
      different from cavosurface angles for air abrasion cavity preparations. Missing
      areas at the cavosurface margin for conventional cavity preparations were not
      significantly different from missing areas at the cavosurface margin for air
      abrasion cavity preparations. Lomb periodograms showed no trend concerning the
      missing area as a function of the angle. CONCLUSIONS: There was no significant
      difference between the area of missing tooth structure at the cavosurface margin
      in conventional vs. air abrasion cavity preparation. Cavosurface angle in
      conventional preparations was less than 90 degrees, and greater than 90 degrees
      in air abrasion cavity preparations. Cavosurface angle and area of missing tooth
      structure at the cavosurface margin varied independently.

PMID- 9545898
TI  - Surface integrity of composite inlays following ultrasonic vibration.
AB  - PURPOSE: To assess the effect of ultrasonic vibration on the surface integrity of
      a resin composite inlay. MATERIALS AND METHODS: Ultrasonic vibration in the form
      of a scaling tip oriented either parallel or perpendicular to the surface was
      applied to 2 mm thick, 10 mm wide composite discs and the experiment was repeated
      with the probe oriented perpendicular using composite or rubber shields. The
      indentations produced were measured using a form Talysurf profilometer. The
      surfaces of the discs were also observed using scanning electron microscopy. Five
      discs were used for each experiment. RESULTS: Both parallel and perpendicular
      orientations produced an indentation with a scattering of composite debris. A
      significant increase in the depth of indentation occurred if the vibrations of
      the ultrasonic scaler were oriented parallel to the composite surface (Two sample
      t- test, P < 0.01). The presence of a composite shield significantly reduced
      (Mann-Whitney, P < 0.05) the depth of indentation but produced roughening of the
      surface with impaction of material from the shield onto the surface. The rubber
      shield, however, polished the surface significantly smoother than the control
      specimens (Mann-Whitney, P < 0.05). Microscope slide separation was used to
      measure the thickness of composite luting agent following vibration with an
      ultrasonic scaling tip with and without a protective sleeve. There was a
      significantly thinner film of luting agent when an unsleeved scaler was used
      (ANOVA, P < 0.001). Although an unguarded tip oriented perpendicular to the
      surface appears to result in the best energy transfer for a thin layer of
      composite luting agent, it does, however, create minimal surface damage.

PMID- 9545899
TI  - Effects of subgingival chlorhexidine irrigation on peri-implant maintenance.
AB  - PURPOSE: To evaluate the effect of irrigation with 0.06% chlorhexidine
      (PerioGard) (CHX) using a powered oral irrigator (Water Pik) with a special
      subgingival irrigating tip (Pik Pocket Subgingival Tip) compared to rinsing with
      0.12% chlorhexidine gluconate once daily. MATERIALS AND METHODS: Following a
      prophylaxis, patients were randomly assigned to an irrigation or a rinse group.
      The following clinical parameters were measured at baseline and at the 3-month
      end of the study: Modified Gingival Index (MGI), Plaque Index (PI), Bleeding
      Index (BI), and Calculus Index (CI). Also, a Stain Index (SI) was measured at 3
      months. RESULTS: Patients irrigating with diluted CHX showed a statistically
      significant reduction (P < 0.05) from their baseline in the MGI, PI, BI, and CI
      scores at 3 months. In the rinse group both MGI and BI showed statistically
      significant reduction from their baseline (P < 0.05) at 3 months. The rinse group
      showed a nonsignificant (P > 0.05) increase from baseline in CI and a
      nonsignificant decrease in PI. Intergroup comparisons showed that CHX irrigation
      produced statistically significantly greater reductions than CHX rinsing in the
      PI, MGI, and SI. The irrigation group also showed a greater reduction in BI and
      CI than the rinsing group but these differences were not statistically
      significant (P = 0.12). The results of this study suggest that use of diluted
      0.06% CHX when used in a powered irrigator may be a valuable adjunct to oral
      health in patients with implants.

PMID- 9545900
TI  - Use of a clear matrix to minimize finishing of a posterior resin composite.
AB  - This article describes the use of a clear matrix to duplicate the original
      occlusal anatomy before placing a posterior resin composite. The technique
      minimizes finishing procedures after the resin composite is placed.

PMID- 9545901
TI  - Dental caries and sugar consumption into the 21st century.
AB  - New trends towards the effect and role of sugar consumption in the etiology of
      dental caries into the 21st century are presented, analyzed and discussed. Many
      factors such as the amount of sugar consumed, the frequency of sugar intake and
      the kind of sugars ingested have to be taken into consideration. Over the years,
      the relative importance of these factors has changed. For a very long time, sugar
      has been "blamed" as a primary etiological factor in the development of dental
      caries. However, a number of recent reports have attributed a much less important
      role to carbohydrates. Sugar consumption only does not affect caries prevalence
      as much as it used to. It is obvious that the role of sugar in the etiology of
      caries must be reviewed. Additional factors like overall nutrition, the number of
      meals and snacks per day, education and motivation, fluoride (in tablets or
      drops, in mouthwashes, toothpastes, baby foods, formulas, beverages, milk,
      vitamin supplements and/or fluoridated water ingested), socioeconomic group,
      ethnicity, oral hygiene status, use of preventive methods and sweeteners other
      than sucrose are presented.

PMID- 9545902
TI  - 2-year clinical evaluation of a gallium restorative alloy.
AB  - PURPOSE: To assess the clinical performance of 2-year old gallium alloy
      restorations. Parameters evaluated include: (1) fracture at the margins, (2)
      tarnish, (3) surface roughness, (4) tooth fracture, (5) fracture through the body
      of the restoration, and (6) any medical or dental conditions arising during the
      study. MATERIALS AND METHODS: Nine patients received 30 Class I restorations of
      Galloy gallium alloy. These were placed as conservatively as possible under a
      rubber dam. Fifteen of the preparations were lined with a Bis-GMA resin to seal
      the restoration from moisture. The other 15 preparations were sealed with
      Amalgambond. After placement of the gallium alloy, the exposed surfaces of all
      restorations were sealed with the Bis-GMA resin, and the occlusion was checked.
      The restorations were examined at 2 weeks, 3 months, 6 months, 1 year and 2
      years. RESULTS: At the 2-year recall, all restorations were intact with the
      exception of one tooth fracture (cause unknown). Forty-five percent of the
      restorations exhibited tarnish and 60% had a rough surface. The fracture at the
      margins of these restorations was minimal, and no significant difference could be
      found between those using Amalgambond and those sealed with the resin system. No
      medical problems were reported by the patients, and postoperative sensitivity was
      minimal.

PMID- 9545904
TI  - Physical properties of composites cured with conventional light or argon laser.
AB  - PURPOSE: To evaluate and compare diametral tensile strength (DTS), compressive
      strength (CS) and flexural strength (FS) of a hybrid and a microfill resin
      composite restorative material polymerized by an argon laser for 10 seconds
      (AL10) and 20 seconds (AL20) vs. a conventional visible light for 40 seconds
      (VL40). MATERIALS AND METHODS: Five specimens of resin composite, Herculite XRV,
      shade A-2 and Durafill VS, shade B-2, were made for each set of physical
      properties tested, for a total of 18 groups and 90 specimens. ANSI/ADA
      Specification #27 for direct filling resins was used as the protocol for specimen
      preparation and physical properties testing. An argon laser at approximately 285
      mW, 6 mm beam size, power density of approximately 1,000 mW/cm2, and a
      conventional visible light at approximately 470 mW, 13 mm beam size, power
      density of approximately 354 mW/cm2, were used to polymerize the composite.
      Samples were stored in water in light-proof containers at 37 degrees C for at
      least 7 days and then tested on a Zwick universal testing machine. Mean DTS, CS
      or FS (MPa) values were calculated for each group. RESULTS: Herculite XRV's
      physical properties were not significantly affected by light source or exposure
      time. Light source or exposure time had no significant effect on DTS for Durafill
      VS. Significantly lower FS was found for Durafill VS, when cured for 10 seconds
      with the argon laser compared to 20 seconds with the laser or 40 seconds with the
      conventional light. In addition, significantly lower CS was found for the
      Durafill VS when polymerized with the laser at 10 seconds compared to the
      conventional light at 40 seconds.

PMID- 9545903
TI  - 3-year clinical evaluation of a compomer, a resin-modified glass ionomer and a
      resin composite in Class III restorations.
AB  - PURPOSE: To evaluate and compare intra-individually a polyacid-modified resin
      composite, commonly called compomer (Dyract), a resin-modified glass ionomer
      cement (RM GIC)(Fuji II LC) and a resin composite (Pekafill) in Class III
      cavities. MATERIALS AND METHODS: In 50 patients, 154 Class III restorations were
      placed. Most patients received one of each of the experimental materials. At
      baseline, 6 months, 1, 2 and 3 years the restorations were evaluated by slightly
      modified USPHS criteria. RESULTS: At 3 years, 152 restorations were evaluated.
      Two restorations were replaced, one due to fracture and one due to secondary
      caries. The resin composite showed significantly better color match. A slight but
      still acceptable color shift and increased surface roughness was seen for the RM
      GIC. The compomer and the resin composite performed significantly better than the
      RM GIC. No postoperative sensitivity was reported and no loss of vitality was
      seen after use of the three different total etch techniques.

PMID- 9545905
TI  - Handling and clinical performance of a glass ionomer sealant.
AB  - PURPOSE: To compare the handling and 6-month clinical performance of an
      experimental resin-modified glass ionomer cement (K-512 = Fuji III LC) with that
      of a light-cured resin-based sealant (Delton Opaque) when used as a pit and
      fissure sealant in 15-27 year old subjects. MATERIALS AND METHODS: Seventeen
      patients with 65 cement and 55 resin-based sealants were recalled after 6 months
      for clinical examination and color photographs. RESULTS: Sealant retention
      failures requiring retreatment were 74% for the glass ionomer cement sealant and
      11% for the resin-based sealant, with one instance of fissure caries being found
      for each material. The resin-modified glass ionomer cement sealant showed a
      slight darkening from its initial placement, and was also more difficult to
      handle than the resin-based sealant.

PMID- 9545906
TI  - Laboratory evaluation of one-component enamel/dentin bonding agents.
AB  - PURPOSE: To evaluate the bonding efficacy of five commercial and one experimental
      one-component enamel/dentin adhesives. MATERIALS AND METHODS: The adhesives One
      Step (BOS), Primabond (PAB), Prime & Bond 2.0 (PB2), Solist (SOL), Tenure Quik
      (TEQ), and an experimental compound (EXP) were investigated. The adhesives were
      used to bond a hybrid-type resin composite to enamel and dentin. Shear bond
      strength (SBS) to human teeth was determined after 24-hour storage in water. The
      marginal performance was evaluated on restorations in 3.5 mm wide cylindrical
      dentin cavities as the maximum gap width found 15 minutes after light activation.
      The hybrid layer thicknesses at the cavity margin were measured by light
      microscopy. RESULTS: Mean SBSs to enamel were between 23 and 35 MPa, those to
      dentin between 3.5 and 25 MPa. BOS and EXP showed the highest bond strengths to
      dentin and consistently gap-free restorations. PB2 mediated significantly lower
      SBS to dentin; only three of the six restorations were gap-free. SOL exhibited
      poor marginal quality (mean MGW 7.5 microns) despite 15 MPa dentin bond strength.
      PAB and TEQ demonstrated very low SBS to dentin. None of the restorations with
      these products was gap-free. All adhesives produced hybrid layers between 2 and
      10 microns thick, as a coupling zone between dentin and restoration. Adhesives
      with the essential components of wetting monomer, well-polymerizing
      dimethacrylate, and acetone as the water-chasing solvent, performed very well
      when used with a moist bonding technique.

PMID- 9545907
TI  - Variation in phosphoric acid concentration and treatment time and HEMA diffusion
      through dentin.
AB  - PURPOSE: The effects of phosphoric acid concentration and time of dentin
      treatment on the movement of 2-hydroxyethylmethacrylate (HEMA) from a bonding
      resin-resin composite combination through dentin were investigated in vitro.
      MATERIALS AND METHODS: Freshly extracted human third molar teeth were divided
      into seven groups each of 10 teeth. A closed chamber was attached to the CEJ of
      each tooth to contain 1 ml distilled water. An occlusal cavity of 6 mm diameter
      and remaining dentin thickness of 1.0-1.5 mm was prepared in each tooth. Dentin
      was treated with either 10% phosphoric acid for 15, 30 or 60 seconds or with 37%
      phosphoric acid for 15, 30 or 60 seconds. A control group not treated with acid
      was also prepared. The cavities were rinsed, dried and then treated with the HEMA
      containing Scotchbond Multi-Purpose bonding resin which was light-cured for 10
      seconds. The cavities were then restored with Z100 and light-cured for 30
      seconds. Water samples were retrieved from the chambers over a time course (4.32,
      14.4, 43.2, 144 & 432 minutes; 1, 3 and 10 days) and analyzed by high performance
      liquid chromatography. RESULTS: HEMA was detected in the pulp chambers of all
      teeth from 4.32 minutes after resin placement. Mean total (cumulative) release at
      10 days for all groups was in the 2-4 mumol range. The highest HEMA diffusion
      rate was 4.32 minutes after placement and were in the range 6-13 times greater
      than control in the 10%-15 seconds, 10%-30 seconds, 10%-60 seconds, 37%-15
      seconds, and 37%-30 seconds groups. Unexpectedly, by far the lowest early rate at
      4.32 minutes was in the 37%-60 seconds group (0.6 times of no-acid control).

PMID- 9545908
TI  - Effects of viscosity and surface moisture on bond strengths of resin-modified
      glass ionomers.
AB  - PURPOSE: To evaluate the effects of surface moisture and material viscosity on
      the shear bond strength of resin-modified glass ionomers to dentin. MATERIALS AND
      METHODS: Sixty human teeth were mounted in phenolic rings and ground to obtain
      flat facial and lingual dentin surfaces. The specimens were assigned to six
      treatment groups. Three groups were first conditioned with 10% polyacrylic acid.
      On one surface of each specimen, dentin was left visibly moist prior to
      application of the restorative material. On the opposite surface the dentin was
      dried, but not desiccated, after conditioning. For these three groups, Fuji II LC
      resin-modified glass ionomer was mixed at powder/liquid (P/L) ratios of 1.4, 3.0
      and 3.6 and applied to the conditioned dentin in 2.5 mm diameter molds. The other
      three groups were treated with Vitremer primer. One surface of each specimen was
      "dry" and one surface was "moist" before primer application. Vitremer restorative
      material was mixed at P/L ratios of 2.2, 2.5 and 2.8 and applied to the primed
      surfaces. Shear bond strengths were measured using a universal testing machine.
      Data were subjected to three-way ANOVA and Tukey's multiple comparisons test.
      RESULTS: Mean shear bond strengths of the two materials ranged from 6.9 to 10.4
      MPa and varied little regardless of the viscosity of the materials or the degree
      of surface moistness. The differences among viscosities and surface moistness
      were not statistically significant. IN this in vitro study, the shear bond
      strengths of two resin-modified glass ionomers were unaffected by the viscosity
      of the materials and the surface moisture of the dentin substrate.

PMID- 9545909
TI  - Bond strengths of fluoride-releasing restorative materials.
AB  - PURPOSE: To compare the shear bond strengths to dentin of four tooth-colored
      fluoride-releasing restorative materials that utilize different mechanisms of
      dentin-bonding. MATERIALS AND METHODS: Four materials were tested: a chemically
      cured glass ionomer (Ketac-Fil); a light-cured resin-modified glass ionomer
      (Photac-Fil); a light-cured resin-modified glass ionomer in conjunction with a
      resin dentin-bonding agent (Vitremer); and a light-cured resin composite in
      conjunction with a resin dentin-bonding agent (Tetric). The enamel was removed
      from four sides of the twenty human noncarious extracted molars which had their
      roots embedded in acrylic blocks. Cylindrical samples of the materials were
      prepared in plastic molds and bonded to the dentin surface according to the
      manufacturers' instructions. After 24 hours of storage in a humidor, the samples
      were sheared with an Instron testing machine at a crosshead speed of 0.5
      mm/minute. RESULTS: Statistical evaluation (ANOVA and Duncan's test) suggests
      that the fluoride-releasing resin composite material utilizing a resin dentin
      bonding agent provided a significantly greater mean shear bond strength (16.5
      MPa) after 24 hours storage than any of the selected glass ionomer materials. Of
      the three glass ionomer materials compared, the light-cured resin-modified
      material with a resin dentin-bonding agent provided a significantly greater mean
      shear bond strength (6.7 MPa) than the light-cured resin-modified material
      without a resin dentin-bonding agent (3.0 MPa) or the chemically-cured material
      (3.8 MPa).

PMID- 9545911
TI  - A fiber composite laminate endodontic post and core.
AB  - The goals of endodontic post and core procedures are to provide maximum retention
      of the post and resistance to fracture of the roots. Presented is a recently
      developed fiber composite laminate (FCL) post and core technique which results in
      a bonded structure that is conservative, morphologic, retentive, versatile,
      esthetic, and helps resist root fracture. To ascertain the durability of FCL
      posts and cores, an in vitro pilot study with stress testing is included. The
      results of the study are compared to other post and core materials to show how
      well this technique approaches the ideal characteristics for endodontic post and
      cores.

PMID- 9545910
TI  - Bond strength to crown and root dentin.
AB  - PURPOSE: To investigate (1) the tensile bond strengths of four commercial dentin
      bonding systems to bovine crown and root dentin and (2) the structure of the
      hybrid layers for each system bonded to the two dentin substrates. MATERIALS AND
      METHODS: Superficial surfaces were exposed in bovine crown and root dentin. The
      teeth were embedded in plaster and a 3 mm diameter bonding area was demarcated.
      The four bonding systems used were All-Bond 2, Super-Bond D-Liner Plus, Clearfil
      Liner Bond II, and ProBond. Bonding procedures followed the manufacturers'
      instructions with the exception of Super-Bond D-Liner Plus where the primer was
      left in situ for 60 seconds. Tensile bond strengths were tested after 24-hour
      storage in 37 degrees C deionized water. Specimens were also prepared for SEM
      observation of the hybrid layer, after treatment with 10% phosphoric acid, and
      10% phosphoric acid and 5% sodium hypochlorite. RESULTS: Statistically lower bond
      strengths to crown dentin when compared with root dentin were observed for All
      Bond 2, whereas Liner Bond II showed the opposite (P < 0.01). Both ProBond and
      Super-Bond D-Liner Plus showed no statistical differences between crown and root
      dentin (P > 0.05). Hybrid layers could be observed for All-Bond 2, Liner Bond II
      and Super-Bond D-Liner Plus, with no apparent differences between the hybrid
      layers of crown and root dentin. In the case of ProBond, where the smear layer
      was not removed during the priming stage, it appeared that the primer had
      infiltrated and caused hybridization of the smear layer. The differences in bond
      strength were thought to be related to the different bonding mechanisms of each
      material, as well as possible variations in the crown and root dentin substrates.

PMID- 9545912
TI  - One step bond strength to enamel and dentin.
AB  - PURPOSE: To evaluate the shear bond strength over a variety of conditions of a
      new dental adhesive having the primer and bonding resin in a single bottle.
      MATERIALS AND METHODS: Facial surfaces of extracted human molars for the dentin
      study and labial surfaces of incisors were treated with the One-Step adhesive
      after both etching and nonetching, variable etching times and variable rinsing
      times. Composite cylinders were attached and shear bond strengths were obtained.
      RESULTS: The bond strength data was quite consistent over a wide variety of
      conditions. The bond strengths were in the range of 23-29 MPa to dentin, and
      compared favorably with the performance of the adhesive to etched enamel
      surfaces.

PMID- 9545913
TI  - Surface treatment effects on amalgam repair strength.
AB  - PURPOSE: To determine whether the use of microetching and bonding agents could
      improve the shear bond strength between aged and freshly added dental amalgam,
      simulating an amalgam repair. MATERIALS AND METHODS: Aged amalgam surfaces were
      treated with either a carbide bur or carbide bur + microetcher (Al2O3 abrasive).
      Five commercially-available adhesive systems were tested. Fresh amalgam was
      condensed through a split mold onto each prepared amalgam surface. Two control
      groups were included: a positive control consisting of non-repaired amalgam, and
      a negative control consisting of aged specimens which received neither carbide
      bur nor microetching preparation prior to the addition of fresh amalgam. In
      addition, one group received only carbide bur and another received only carbide
      bur and microetching treatments, without any adhesive. Following storage and
      thermocycling, each specimen was tested for shear bond strength. RESULTS: The
      mean shear bond strength of the repaired samples treated with carbide bur alone
      (25.8 MPa) was not exceeded by any of the other treatments. Neither microetching
      nor use of an adhesive agent significantly improved amalgam-to-amalgam shear bond
      strength. In some cases, use of an adhesive agent significantly decreased the
      shear bond strength of repaired amalgam samples.

PMID- 9545914
TI  - Surface hardness and wear of glass ionomers and compomers.
AB  - PURPOSE: To determine the surface hardness and in vitro wear of glass ionomer
      cements (GIC) and compomers in comparison with a resin composite and to test for
      a possible correlation between the determined hardness and wear values. MATERIALS
      AND METHODS: Samples were made of conventional GIC (Ketac-Fil, Fuji II, Fuji IX,
      Ketac-Prototype = Ketac-Molar), resin-modified GIC (Photac-Fil, Fuji II LC,
      Vitremer), compomers (Dyract, Compoglass) and resin composite (Z100) for the
      hardness test (n = 10) and for the wear test (n = 3). The materials were handled
      according to the manufacturers' instructions. The samples were stored in
      deionized water for 48 hours at 37 degrees C prior to the determination of
      Rockwell hardness and three-body in vitro wear. RESULTS: Hardness could not be
      measured on Ketac-Fil and Fuji II as the samples fractured before a reading was
      obtainable. Statistically significant differences were found in hardness and wear
      between brands and between the four types of material. Surface hardness: resin
      modified GIC < conventional GIC = compomers < resin composite. In vitro wear:
      resin-modified GIC > compomers > conventional GIC > resin composite. A negative
      correlation between hardness and wear was recorded.

PMID- 9545915
TI  - Clinical evaluation of glass ionomers and compomers in Class V carious lesions.
AB  - PURPOSE: To evaluate the 2-year clinical performance of two polyacid-modified
      resin composites and two resin-modified glass ionomers in Class V carious
      cavities. MATERIALS AND METHODS: A total of 120 Class V cavities were selected
      and 30 cavities were restored with one of two resin-modified glass ionomer
      materials (Fuji II LC Improved and Vitremer) and two polyacid-modified resin
      composites (Dyract and Compoglass) in Class V carious cavities after 2 years. The
      restorations were clinically evaluated after 1 and 2 years using the USPHS
      criteria. RESULTS: One-year findings revealed a significant difference in color
      match between Vitremer and other materials (P < 0.05) and no significant
      difference was found for the other criteria. Two-year results indicated a
      significant difference between resin-modified glass ionomers and polyacid
      modified resin composite materials. The difference between Compoglass and Dyract
      was not statistically significant whereas the difference between Vitremer and
      Fuji II LC was statistically significant. Caries was not recorded at any
      evaluation period.

PMID- 9545916
TI  - Dentin desensitizing agents: SEM and X-ray microanalysis assessment.
AB  - PURPOSE: To evaluate the effect of four proprietary dentin desensitizing agents
      on dentin tubular occlusion, chemical composition changes on the dentin surface,
      and the effect of saliva and toothbrushing on these agents. MATERIALS AND
      METHODS: Fifty dentin discs, obtained from 50 freshly extracted human premolar
      and molar teeth were used in this study. These were divided into five groups of
      10 discs each. Five discs from each group were treated with the desensitizing
      agents, viewed under the SEM and subjected to energy dispersive X-ray analysis.
      The other five discs were treated with the desensitizing agents, immersed in
      artificial saliva, subjected to simulated toothbrushing equivalent to 3 weeks of
      normal brushing and viewed under the SEM. The agents studied were Sensodyne
      Dentin Desensitizer, Therma-Trol Desensitizer Gel, Gluma Desensitizer and All
      Bond DS. RESULTS: The Kruskal-Wallis test followed by the Wilcoxon signed-rank
      test showed that Sensodyne Dentin Desensitizer exhibited the greatest amount of
      tubular occlusion among the unbrushed samples, followed by Therma-Trol
      Desensitizer Gel, Gluma Desensitizer and All-Bond DS (P < 0.05) in that order.
      Toothbrushing increased tubular occlusion in all cases except the Sensodyne
      Dentin Desensitizer treated samples.

PMID- 9545917
TI  - Dentin bond strength of Dyract Cem.
AB  - PURPOSE: To evaluate the influence of provisional cements and of a dentin bonding
      agent on the adhesion of a self-curing polyacid-modified resin composite (Dyract
      Cem) on pressurized human dentin. MATERIALS AND METHODS: Freshly prepared dentin
      specimens of human teeth were perfused with physiologic saline. Three different
      types of surface treatment were evaluated. (1) Dyract Cem was applied to freshly
      prepared dentin without (Group 1.1) or with (Group 1.2) the respective dentin
      bonding agent (Prime & Bond 2.0) and cured. (2) Freegenol (Groups 2.1 and 2.2) or
      Temp Bond (Groups 2.3 and 2.4) were applied first on the dentin surface for 24
      hours. Only then was Dyract Cem (with or without Prime & Bond 2.0) added onto the
      dentin after cleaning the dentin surface with pumice. 3) Prime & Bond 2.0 was
      applied first on the dentin surface and cured. Then Freegenol (Group 3.1) or Temp
      Bond (Group 3.2) were added for 24 hours. After cleaning with pumice, Prime &
      Bond 2.0 was applied for a second time on the dentin (= dual application) and
      finally Dyract Cem was added. As control, a conventional glass ionomer cement
      (Ketac-Cem Maxicap; Groups 4.1-4.3) was used in a similar way. After 1,500
      thermal cycles with constant imitation of intrapulpal pressure, shear bond
      strengths were measured. Resulting shear bond strength values were displayed by
      means of a box plot and they were analyzed statistically by Mann-Whitney, Kruskal
      Wallis or one way ANOVA tests. RESULTS: Lowest and highest mean shear bond
      strength values were 0.27 +/- 0.42 MPa (Group 2.4; single use of Prime & Bond 2.0
      with prior application of TempBond) and 5.84 +/- 3.36 MPa (Group 3.1; dual use of
      Prime & Bond 2.0 with intermediate application of Freegenol). A clearly
      significant difference between groups could only be found when a single or dual
      use of the dentin bonding agent Prime & Bond 2.0 were combined with either
      Freegenol (Groups 2.1, 2.2 and 3.1; Kruskal-Wallis: P < 0.01) or Temp Bond
      (Groups 2.3, 2.4 and 3.2; Kruskal-Wallis: P < 0.001) as additional dentin surface
      treatment.

PMID- 9545918
TI  - Effect of cavity design on microleakage of resin-modified glass ionomer
      restorations.
AB  - PURPOSE: To investigate cavity sealing with resin-modified glass ionomer cements
      (RGIC) and a compomer relative to the design of Class V cavities crossing the
      CEJ. MATERIALS AND METHODS: Three types of cavities, 6 x 3 x 1.5 mm, were
      prepared buccally in human molars. Type 1: semicircular with 90 degrees cavo
      surface angle; Type 2: as type 1, but with bevelled enamel margin; Type 3: V
      shaped. The cavities were restored with the compomer Dyract (DYR), with one of
      the RGIC, Fuji II LC (FUJ), Photac-Fil (PHF) or Vitremer (VIT), or with the
      bonded resin composite system Gluma-CPS/Pekafill (GLP) as a reference. Six
      restorations in each group were finished immediately after curing and
      thermocycled 1500 between 5 degrees C and 55 degrees C. For Type 1 restorations,
      another set of six samples was stored in 23 degrees C water for 24 hours. After
      thermocycling and water storage, respectively, the specimens were immersed in
      0.1% fuchsin. Two sections were made through the restoration to register
      microleakage on the four surfaces produced as depth of dye penetration coronally
      and apically by scores 0 (no) to 4 (beyond deepest part of cavity). The results
      were statistically analyzed by cavity type, site, and restorative material using
      Kruskal-Wallis ANOVA and Wilcoxon's two sample test at P = 0.05. RESULTS: When
      compared with water storage, thermocycling had no effect on dye penetration with
      FUJ and PHF, yet more pronounced microleakage at the enamel site was noted with
      DYR and VIT, and apically with DYR and GLP. Type 1 restorations leaked more than
      type 2 and 3 cavities for FUJ, VIT and GLP.

PMID- 9545919
TI  - Rechargeability of fluoride releasing pit and fissure sealants and restorative
      resin composites.
AB  - PURPOSE: To evaluate the effect of exposure of 1.23% acidulated phosphate
      fluoride gel on fluoride release from fluoride releasing pit and fissure sealants
      and restorative resin composites. MATERIALS AND METHODS: Specimens of four
      fluoride releasing pit and fissure sealants (Helioseal F, Ultraseal XT, Seal Rite
      Low Viscosity and Seal Rite-Regular Viscosity) and two fluoride releasing
      restorative resin composites (Tetric and Heliomolar Radiopaque) were prepared
      using a Teflon mold. The specimens were divided into two groups. The experimental
      group was exposed to 1.23% acidulated phosphate fluoride gel and the control
      group was exposed to 1.23% acidulated phosphate gel without fluoride. The
      specimens were stored in deionized water and the fluoride concentration of the
      solution was measured every 24 hours. On day 7, the discs were exposed to the
      respective gel for 4 minutes and then rinsed in a continuous stream of deionized
      water for 30 seconds. The fluoride concentration was then measured for another 7
      days. RESULTS: There was a significant increase after the fluoride gel treatment
      in the amount of fluoride released from all of the materials studied. When the
      cumulative amount of fluoride released was evaluated, Tetric, Heliomolar
      radiopaque, Helioseal F, and Ultraseal XT released significantly (P < 0.01) more
      fluoride than the respective control groups. There was no significant difference
      between groups from day 8 to day 14 for Seal Rite-Regular Viscosity and Seal Rite
      Low Viscosity.

PMID- 9545920
TI  - Effect of implant curets on titanium implant surfaces.
AB  - PURPOSE: To compare the surface roughness produced by various implant curets on
      titanium implant abutment surfaces. MATERIALS AND METHODS: Each of six titanium
      implants was divided into four quadrants, three experimental and an untreated
      control surface. The three experimental surfaces were instrumented with a gold
      platinum curet, an unreinforced resin curet, or a reinforced resin curet. Two
      implants were assigned to each of the following treatments: 128, 256 or 512
      scaling strokes within a 4 mm wide area. Photographs were taken of the surfaces
      with a scanning electron microscope at approximately x500 magnification and
      classified by six investigators according to surface roughness. RESULTS: The
      surfaces were different at 8 and 16 years with P < 0.01 and P < 0.0005,
      respectively. At 8 years, the surface roughness was significant between the
      treatments in the following ascending order: untreated, unreinforced resin curet,
      reinforced resin curet and gold platinum curet. Significant roughness was
      observed for surfaces treated by only the gold platinum curet and the reinforced
      resin curet at 16 years. The gold platinum curet created the roughest surface P <
      0.0006.

PMID- 9545921
TI  - Effect of fit adjustment on CEREC CAD-CAM veneers.
AB  - PURPOSE: To measure and compare the adaptation of CEREC CAD-CAM porcelain veneers
      with and without fit adjustment. MATERIALS AND METHODS: Two groups of porcelain
      veneers were fabricated using the CEREC CAD-CAM technique for standardized
      preparations on 10 artificial teeth. Mesial preparation contacts were broken, but
      distal contacts remained intact. One group was adjusted using a disclosing spray
      to improve fit, another group made for the same teeth was not adjusted before
      cementation. The veneers were cemented in a standardized manner to their teeth.
      The veneers and their attached cement were retrieved, embedded in epoxy resin and
      sectioned twice to produce eight sections. Each section was measured at three
      defined points from the external surface inwards. RESULTS: Three-way ANOVA
      disclosed that fit adjustment was relatively ineffective (P approximately 0.05),
      but that measurement section location, measurement point location and their
      interaction significantly affected fit (P < 0.05). Restoration of the broken
      proximal contact, or simulated diastema closure did not compromise fit. Incisal
      margins ranked worst for fit. Surface measurement point locations ranked worse
      than internal points. The fit of these CEREC CAD-CAM veneers was not
      substantially different from previously published fit values for conventional
      porcelain veneers.

PMID- 9545922
TI  - Clinical application of a direct placement mercury-free alloy.
AB  - This article provides information about a recently introduced, mercury-free
      restorative alloy. This direct placement alloy uses gallium rather than mercury
      to mix the alloy particles. The material has recently been approved for use in
      the United States. Although its handling and physical properties are similar in
      most ways to amalgam, there are a few differences that require careful attention
      to assure success for the restoration. This article discusses these handling
      characteristics, the procedures for placement, and offers specific directions and
      recommendations to avoid potential problems with its use. Information on recent
      clinical research is included in the article.

PMID- 9545923
TI  - One visit composite onlay utilizing a new flexible model material.
AB  - Fabrication of a composite inlay/onlay utilizing a flexible model is described as
      a direct alternative to direct composite placement.

PMID- 9545924
TI  - The need for well-controlled clinical studies.

PMID- 9545925
TI  - Immediate loading of Branemark implants in edentulous mandibles: a preliminary
      report.
AB  - A study involving the immediate loading of Branemark implants in the edentulous
      mandibles of 10 patients is reported. The design involved the immediate loading
      of four widely distributed implants with a transitional fixed implant-supported
      prosthesis at first-stage surgery, avoiding the need for a removable prosthesis.
      A sufficient number of additional implants are allowed to heal in the
      conventional manner to provide sufficient support for a definitive fixed
      prosthesis even if all of the immediately loaded implants fail. Preliminary
      results have been favorable, with all patients functioning with a fixed implant
      prosthesis from the day of first-stage surgery.

PMID- 9545926
TI  - Osteoconductive properties and efficacy of resorbable bioactive glass as a bone
      grafting material.
AB  - The height of the available bone between the alveolar ridge and the sinus is
      often insufficient for placing endosseous implants in the posterior maxilla.
      Subantral augmentation after sinus elevation can be performed using bone-grafting
      materials such as autogenous bone, allografts, and alloplasts. The properties and
      performance of a recently developed resorbable bioactive glass (BioGran) were
      investigated with regard to bioactivity and bone-forming capability. The
      bioactive glass was grafted into the sinus cavities of 25 patients and biopsies
      were taken after 7 months. The samples were examined by conventional histologic
      techniques, elemental composition and distribution assayed by an electron probe
      microanalyzer, and comparative biomechanical data for BioGran and bone tissue
      gathered. Histologic and biomechanical examination indicated bone formation in
      all cases, with biomechanical properties of the regenerated bone close to those
      of bone tissue. The results of this study suggest that BioGran exhibits
      osteoconductive properties and efficacy as an alloplastic bone-grafting material.

PMID- 9545928
TI  - Long-term efficacy of hydroxyapatite-coated cylindrical implants.
AB  - A two-site clinical study of hydroxyapatite-coated cylindrical titanium alloy
      implants was undertaken to evaluate their efficacy. Observations were recorded
      before surgery, at first-stage surgery, at second-stage surgery, at loading, and
      at quarterly postrestoration prophylactic examinations and annual comprehensive
      patient visits. Implant failure criteria included mobility, peri-implant
      radiolucency, fracture, exfoliation, removal for any reason, and patient reported
      pain on palpation. Soft tissue indices were monitored as part of the study.
      Postrestoration implant performance was analyzed using life table methodology.
      From the 316 implants restored in 154 patients, 11 implants in 8 patients failed
      before prosthetic attachment, for a surgical success rate of 96.4 percent. Four
      implants failed during an observation period extending up to 85 months after
      completion of prosthetic treatment. The Cutler-Ederer life table success rate
      after 6 years was 97.8 percent. No significant adverse events were reported
      during the observation period. Results of this investigation suggest that
      hydroxyapatite-coated cylindrical titanium alloy implants are an effective
      treatment modality.

PMID- 9545927
TI  - Reconstruction of a severely atrophic maxilla using a Le Fort I downgraft and
      dental implants: clinical report.
AB  - A 55-year-old woman developed chronic infections of the maxillary sinuses with
      osteomyelitis resulting in extensive bone destruction and atrophy from a failed
      subperiosteal implant. After surgical removal of the subperiosteal implant,
      extensive debridement of the maxilla, and long-term antibiotic therapy, maxillary
      reconstruction was initiated. A Le Fort I osteotomy and downgraft was performed,
      and a posterior iliac bone graft was harvested and grafted to reconstruct the
      severely atrophic maxilla. In a later surgical procedure, maxillary and
      mandibular implants were placed. Implant-retained overdentures were fabricated to
      restore function and esthetics.

PMID- 9545929
TI  - Fitting and securing abutments to implant heads: technical note.
AB  - Access and visualization in the implant-abutment area are often compromised.
      Tissue impingement and lack of abutment position verification may result in
      inaccurate fit.

PMID- 9545930
TI  - The Second International Implantology Congress. Bangkok, Thailand, January 18-20,
      1997. Abstracts.

PMID- 9545931
TI  - Evaluation of the antibacterial activities of calcium hydroxide, chlorhexidine,
      and camphorated paramonochlorophenol as intracanal medicament. A clinical and
      laboratory study.
AB  - The antibacterial activities of camphorated paramonochlorophenol, chlorhexidine,
      and calcium hydroxide were compared using a clinical and laboratory evaluation.
      In the clinical experiment, root canals that yielded positive cultures a week
      after complete chemomechanical preparation and camphorated paramonochlorophenol
      dressing were medicated with one of the three substances tested. Postmedication
      samples were taken from the canal 1 week later. In the laboratory experiment, the
      agar diffusion test was used to evaluate the inhibitory activity of the
      medicaments against bacteria commonly found in endodontic infections. The results
      of the clinical evaluation showed that all medicaments were effective in reducing
      or eliminating the endodontic microbiota, as demonstrated by the incidence of
      negative cultures. There was no statistically significant difference among the
      medicaments tested. In the laboratory evaluation, camphorated
      paramonochlorophenol showed the largest zones of bacterial inhibition against all
      bacterial strains tested.

PMID- 9545932
TI  - Root canal cleanliness after preparation with different endodontic handpieces and
      hand instruments: a comparative SEM investigation.
AB  - The root canals of 150 extracted mandibular incisors were prepared to ISO 30
      using eight different automated devices and hand instruments. The automated
      devices investigated were: Endoplaner, Excalibur, Ultrasonics (Piezon Master 400)
      with H2O2 (5%), or NaOCl (1%) as irrigants, Giromatic, Intra-Endo 3-LDSY, Canal
      Finder System, Canal Leader 2000, and Endolift. Hand instrumentation was
      performed using reamers and Hedstroem files. Fifteen teeth were instrumented with
      each device, cracked longitudinally, and investigated under the scanning electron
      microscope using five category scoring systems based on reference photographs for
      debris and smear layer. No preparation system or technique resulted in complete
      removal of smear layer and debris. The ultrasonic unit performed best followed by
      the Canal Leader 2000 and hand instrumentation, whereas the use of the Giromatic,
      the Endolift, the Canal Finder System, and the Intra-Endo-3-LDSY-handpiece
      resulted in insufficiently cleaned root canal walls.

PMID- 9545933
TI  - Warm vertical compaction sequences in relation to gutta-percha temperature.
AB  - The aim of this study was to analyze warm vertical compaction sequences in
      relation to the temperature variations of gutta-percha. Twenty-four maxillary
      incisors were obturated according to two different instrumentation techniques:
      Compaction and heating were performed with either the monomanual classical or
      bimanual method. To evaluate gutta-percha temperature, thermocouples (TC) were
      introduced into channels bored through the dentin into the root canal system or
      fixed on the root surface at 8 (TC8), 4 (TC4), 2 (TC2), and 0 mm (TC0) from the
      apex. Maximal temperature was 118 degrees C for TC8, 52 degrees C for TC4, and 44
      degrees C for TC2 and TC0. At TC0, the temperature remained above 42.9 degrees C
      for 10 +/- 5 s. These results show the importance of heating down to a distance
      of 7 mm to ensure a significant increase in apical gutta-percha temperature. They
      further indicate that the last compaction should last more than 15 s to avoid
      detrimental cooling and dimensional variations. The principal differences between
      the monomanual and bimanual methods were the compaction time (5.07 +/- 0.2 min vs
      4.02 +/- 0.3 min) and the number of compactions (8 +/- 1 vs 12 +/- 2).

PMID- 9545934
TI  - An in vitro comparison of apical microleakage after obturation with JS Quick-Fill
      or lateral condensation.
AB  - Thirty extracted human single-root teeth were instrumented to #45 file size while
      creating a continuous coronal taper. Canals were obturated with Roth 801 sealer
      and either JS Quick-Fill or lateral condensation of gutta-percha. Mean apical
      linear microleakage of India Ink was evaluated in cleared teeth using a
      stereomicroscope. Significantly less leakage (p < 0.1) occurred with lateral
      condensation than with JS Quick-Fill.

PMID- 9545935
TI  - Comparison of the intraosseous biocompatibility of Dyract and Super EBA.
AB  - The purpose of this study was to compare the intraosseous biocompatibility of
      Dyract, a new hydrophilic glass-ionomer cement, to that of Super EBA. Twenty-four
      New Zealand rabbits were anesthetized, one leg was shaved, the femur exposed, and
      two holes were drilled through the cortical plate. The materials were loaded into
      silicone carriers and inserted into the femur. Half of the rabbits were killed 4
      weeks after implantation and the other half at 12 weeks and the femurs were
      prepared using standard histological procedures. The tissue reactions were graded
      from none to severe. At 4 weeks both materials showed slight to moderate
      reactions, characterized by the presence of fibrous tissue interposition and
      inflammatory cells. At 12 weeks, bone healing had occurred, despite the
      persistence of some fibrous tissue interposition, and the reactions were
      classified as slight. At both observation periods, statistical analysis failed to
      show any difference between the two materials indicating that Dyract and Super
      EBA had similar intraosseous biocompatibility.

PMID- 9545936
TI  - Microleakage of temporary restorations after thermocycling and mechanical
      loading.
AB  - The marginal seal of four temporary filling materials in endodontic access
      cavities was examined in vitro after thermocycling and mechanical loading using
      dye penetration tests and a quantitative marginal analysis of replicas in the
      SEM. Class I cavities were prepared in 44 extracted human molars and filled
      either with Cavit, Kalsogen, IRM, or TERM. After setting the reaction and
      thermocycling procedure, Cavit showed less microleakage in the dye penetration
      test and fewer marginal crevices in the quantitative marginal analysis. After
      loading, two Cavit fillings collapsed into the endodontic cavity. The marginal
      conditions of TERM were comparable to Cavit after thermocycling and mechanical
      loading. Kalsogen and IRM restorations demonstrated significantly increased
      microleakage and a higher percentage of marginal crevices after thermocycling and
      loading. In contrast to dye penetration tests, the effects of different factors
      on the marginal integrity of temporary fillings can be examined with the replica
      technique and quantitative marginal analysis.

PMID- 9545937
TI  - Evaluation for cracks associated with ultrasonic root-end preparation of gutta
      percha filled canals.
AB  - Many clinicians use ultrasonics for root-end preparations. The purpose of this
      study was to evaluate resected root-end surfaces of bilaterally matched human
      teeth for cracks before and after ultrasonic root-end preparation. Twenty matched
      pairs of extracted single rooted teeth were divided into two experimental groups.
      In group 1, root-end resection was performed on uninstrumented teeth. In group 2,
      root-end resection was performed after the canals were instrumented and filled
      with gutta-percha. All teeth in both groups received root-end preparations using
      ultrasonic instrumentation at low power. Two examiners evaluated the root-ends
      after root-end resection and again after root-end preparation using zoom
      magnification of 20x to 63x. The number, types, and location of cracks were
      mapped. There were no significant differences when gutta-percha filled roots were
      compared to uninstrumented roots with regard to the number or type of cracks
      after root-end resection or root-end preparation. In addition, there were no
      significant differences in the number or type of cracks following root resection
      and ultrasonic root-end preparation when compared to teeth with root resection
      alone.

PMID- 9545938
TI  - An ultrastructural study of root canal walls in contact with endodontic
      biomaterials.
AB  - The aim of this in vitro study was to compare structural and ultrastructural
      changes to the unmineralized extracellular matrix after using two root canal
      restoration materials, one calcium hydroxide based and the other calcium oxide
      based. Pig teeth were restored with no preliminary root canal preparation. The
      filling materials were left in the root canals for 3, 8, 15, or 21 days.
      Observations were carried out by scanning electron microscopy. Results showed
      that when the calcium oxide-based material was used, it penetrated tubules and
      the unmineralized extracellular matrix material was reduced to a minimum. Teeth
      filled with the calcium hydroxide-based material were similar to control samples
      with an intact predentine. These observations suggest that the calcium oxide
      based material induces changes in the unmineralized extracellular matrix of the
      endodontium.

PMID- 9545939
TI  - Leakage of AH26 and Ketac-Endo used with injected warm gutta-percha.
AB  - Condensing warm gutta-percha (GP) can greatly reduce the distance between the GP
      and the root canal walls (RCW). Different sealers with different film thicknesses
      may seal such close fits differently. With the use of a fluid transport model,
      leakage of AH26 and Ketac-Endo used with injected warm GP to fill root canals was
      measured. The distance between the condensed GP and RCW and the film thickness of
      the two sealers was determined as well. After condensation, the distance between
      GP and RCW was mostly less than 25 microns. AH26, with a film thickness of 39
      microns, leaked more than Ketac-Endo (p < 0.05) of which the film thickness was
      22 microns. It seems that film thickness of sealer is an influencing factor on
      the sealing ability of a root canal filling when condensation of
      thermoplasticized GP is performed.

PMID- 9545940
TI  - Atypical odontalgia misdiagnosed as odontogenic pain: a case report and
      discussion of treatment.
AB  - Atypical odontalgia is characterized by prolonged periods of throbbing or burning
      pain in the teeth or alveolar process, which occurs in the absence of any
      identifiable odontogenic etiology. The pain may be bilateral and change in
      location. This article presents two cases of atypical odontalgia that were
      misdiagnosed and initially treated as pain of odontogenic origin. A therapeutic
      regimen of tricyclic antidepressants alleviated the pain in one patient and was
      unsuccessful in the second. These two cases demonstrate the importance of having
      a thorough knowledge of both odontogenic and nonodontogenic causes of orofacial
      pain as well as the need for careful diagnosis before undertaking any treatment.

PMID- 9545941
TI  - Analysis of forces developed during obturations. Comparison of three gutta-percha
      techniques.
AB  - The aim of this study was to compare the forces developed during three obturation
      techniques: warm vertical compaction (WVC), lateral condensation (LC), and
      thermomechanical compaction (TMC). A force-analyzer device allowed us to record
      and analyze the forces exerted during the obturations. The different methods,
      which varied in instrumentation, duration, and compaction load, were studied from
      graphs representing the force application sequences. In addition, the graphs
      resulting from specific modifications in the LC technique (use of a single
      spreader) and deliberately induced failures with TMC (with a too-small condensor
      or with excessive load) were analyzed. The mean values for the vertical forces
      for WVC, LC, and TMC were, respectively, 2.5 +/- 0.4 kg, 1.1 +/- 0.3 kg, and 1.65
      +/- 0.2 kg. The mean values for the lateral forces were, respectively, 0.85 +/-
      0.2 kg, 0.35 +/- 0.1 kg, and 0.5 +/- 0.2 kg. The use of graphs provides a new
      approach to the analysis of obturation methods and may find its greatest
      application in the teaching of these techniques. It also has the potential to
      improve research into obturation technique.

PMID- 9545942
TI  - Comparison between Sulphorhodamine-B dye staining and 51Cr-release method in
      cytotoxicity assay of endodontic sealers.
AB  - The aim of this study was to evaluate Sulphorhodamine-B (SRB) staining against
      51Cr-release in cytotoxicity tests of six endodontic sealers, namely, MU sealer
      (Mahidol University) ROCANAL 2, ROCANAL 3, Apexit, Endomethasone, and AH-26.
      Monolayers (5 x 10(5) cells/ml) of the mouse cell line Mu-mu-1 were used as test
      cells. Following incubation at 37 degrees C in 5% CO2 for 24 h in the presence of
      each sealer, cells were stained with 0.4% SRB and the absorbance at 540 nm
      determined as measure of cell viability. For 51Cr-release assay, cells were
      labelled with 51Cr before testing with sealers, and radioactivity in the
      supernatant was measured in a liquid scintillation counter. Both techniques
      indicated that Apexit was the least toxic sealer. In view of the ease of
      conducting SRB staining for tests of cell viability, this may be the method of
      choice over 51Cr-release assay in the evaluation of endodontic sealer
      cytotoxicity.

PMID- 9545943
TI  - The degrees and configurations of mesial canal curvatures of mandibular first
      molars.
AB  - The objective of this study was to determine the frequency, degree of curvature,
      and the configuration of mesiobuccal and mesiolingual root canals of mandibular
      first molars. The degree of curvature and configuration of root canals creates
      some technical difficulties to the clinician during biomechanical preparation.
      Therefore this knowledge is essential for successful endodontic therapy. Six
      hundred and ninety-seven freshly extracted mandibular first molars were used in
      this study. After introducing 0.8 to 15 K reamers into the mesial root canals,
      the teeth were radiographed in buccolingual (clinical) and mesiodistal (proximal)
      directions. All samples showed curvatures at varying degrees in both views. There
      was a significant correlation between the degree of primary curvature of
      mesiobuccal and mesiolingual canals in clinical directions for total samples.
      When the primary curvature values of the mesial root canals were evaluated in
      Vertucci classification, the mesiobuccal and mesiolingual canals in Vertucci type
      VI were found as significantly correlated (r = 0.7173, p < 0.05). A significant
      correlation was seen between the secondary curvature values of clinical and
      proximal views of mesiolingual canal in Vertucci type VI (r = 0.9891, p < 0.05).
      The secondary curvature values in the clinical views of mesiobuccal and
      mesiolingual canals were found as significantly correlated in Vertucci type II.

PMID- 9545944
TI  - Detection of human IL-2 in normal and inflamed dental pulps.
AB  - Irreversible pulpitis has been associated with an increase in the number of
      pulpal T-cells. Interleukin-2 (IL-2) stimulates T-cell proliferation and signals
      the release of other proinflammatory mediators associated with connective tissue
      degradation. IL-2 has been suggested to be a useful marker of pathologic
      inflammatory activity in periodontal and systemic disease conditions. The purpose
      of this study was to analyze normal and inflamed dental pulps for the presence of
      immunoreactive IL-2 (iIL-2). Normal healthy pulpal tissue was obtained from 17
      impacted third molars and inflamed samples were obtained from 12 symptomatic
      carious molars clinically diagnosed with irreversible pulpitis. Pulpal tissues
      were collected, prepared, and analyzed for histological status and iIL-2
      concentration by a modified ELISA technique. iIL-2 was detected in all vital
      pulpal tissues. A t-test revealed significant differences in iIL-2 concentrations
      when inflamed pulpal tissues were compared to normal healthy samples (T = -2.75,
      p < 0.05). These results suggest that iIL-2 may serve as a marker of pathologic
      inflammatory activity in irreversible pulpitis.

PMID- 9545945
TI  - Cytotoxicity of Ketac Silver cement.
AB  - The aim of this experiment was to investigate the effect of a glass ionomer
      cement with silver particles (Ketac Silver) on pulp tissue. Class V cavities were
      prepared in 60 healthy teeth scheduled for extraction for orthodontic reasons. A
      base of Dycal was placed in each cavity. Thirty teeth were filled with Ketac
      Silver and 30 with ZOE. Ten teeth of each group were extracted 15, 30, and 60
      days later. At 15 days, the pulps in the Ketac group showed vacuolization and
      disruption of the odontoblastic layer, edema, vasodilation, chronic inflammatory
      infiltrate (CII), and necrosis. At 30 days, a necrotic odontoblastic layer,
      severe CII, and extensive areas of necrosis were seen. At 60 days, pulp tissue
      was almost completely necrotic. The ZOE control group showed a slight CII at 15
      days. Our results suggest that under these experimental conditions, this cement
      is highly toxic and induces irreversible pulpal damage.

PMID- 9545946
TI  - Osteocalcin expression in young and aged dental pulps as determined by RT-PCR.
AB  - Dental pulps were obtained from third molars of young adults (17-25 yr) or from
      molar teeth of individuals > 50 yr of age and examined for the expression of
      osteocalcin (OC) mRNA by RT-PCR. OC was selected as a determinant of pulp
      vitality, because it has long been associated with the production of hard tissue
      matrix in teeth and bone. For comparative purposes, the expression of OC in each
      pulp was normalized relative to its housekeeping gene-product GAPDH by the
      establishment of a OC/GAPDH ratio. This study demonstrated that OC expression,
      presumably by cells of odontoblast lineage, does not diminish relative to the
      extant cell population. Our findings suggest, despite a reduction in volume and
      cell numbers, that the pulps of aging teeth retain a capacity for dentin
      deposition and a potential for caries and trauma resistance.

PMID- 9545947
TI  - Recombinant human osteogenic protein-1 induces dentin formation: an experimental
      study in miniature swine.
AB  - It was the aim of the present study to investigate the induction of dentin
      formation by recombinant human osteogenic protein-1 (hOP-1). In 4 adult miniature
      pigs a total of 16 teeth with artificially exposed dental pulps were capped with
      3 mg of a complex of recombinant hOP-1 in collagen matrix (2.5 micrograms/mg),
      collagen matrix alone, or calcium hydroxide paste. Teeth were removed in block
      section after a healing period of 5 weeks. Decalcified sections were processed
      for light microscopy and histomorphometric analysis. In hOP-1 treated teeth
      substantial amounts of hard tissue formation (osteodentin and tubular dentin) had
      consistently led to a complete bridging of the defects. Less dentin formation was
      seen after calcium hydroxide application. In control defects collagen matrix
      alone failed to form complete dentin bridges. Recombinant human osteogenic
      protein-1 in a collagen carrier matrix appeared to be suitable as a bio-active
      capping agent for surgically exposed dental pulps.

PMID- 9545948
TI  - A comparison of molar root canal preparations using six instruments and
      instrumentation techniques.
AB  - Six different instruments (Flexofile, Canal Master U, Heliapical, Flexogate,
      Ultraflex, and Lightspeed) were evaluated in 240 mesial canals of extracted
      mandibular molars (40 canals per instrument type). After instrumentation, the
      roots were cross-sectioned 2, 5, and 9 mm from the apex. The cross sections were
      evaluated to determine the quality of canal preparation (round, oval, irregular).
      The best results were obtained with nickel-titanium, a short cutting blade and a
      rotary rather than a filing motion. The Canal Master U, Flexogate, and Lightspeed
      instruments had significantly more round canals than the Flexofile, Heliapical
      and Ultraflex instruments at all levels. The Lightspeed had the largest number of
      round canals at all levels. Instrumentation time was also recorded. The Canal
      Master U and Flexogate were significantly slower than the Flexofile, heliapical,
      Ultraflex, and Lightspeed instruments. There were no statistically significant
      differences within the faster group.

PMID- 9545949
TI  - In vitro study of intradentinal calcium diffusion induced by two endodontic
      biomaterials.
AB  - The aim of this in vitro study was to assess intratubular calcium penetration
      induced by two root canal restoration materials, one calcium oxide based, and the
      other calcium hydroxide based. Pig teeth were restored with no preliminary root
      canal preparation. The filing materials were left in place for 8, 15, or 21 days.
      The samples were then examined using various microanalytical techniques and, in
      parallel, by backscattered electron image (BEI) scanning electron microscopy. The
      Ca/P ratios obtained by microanalysis were higher for samples restored with
      calcium oxide. In addition, the distances over which the ratios increased were
      also greater than those obtained using calcium hydroxide. BEI photographs confirm
      these results and show corresponding retrodiffusion fringes.

PMID- 9545950
TI  - Penetration of constricted canals with modified K files.
AB  - A technique using K files with modified tips has been developed for the
      penetration of constricted canals. The tip of a #10 K file was sliced diagonally
      to make it thinner. Because this modified K file has an especially fine tip and
      an appropriate stiffness, it followed constricted or sharply curved canals well
      and had a high penetration potential. The author attempted to penetrate to the
      apical foramen in all 1844 canals of 977 teeth treated from 1987 to 1994. In 263
      canals (14.3%) that could not be penetrated with conventional #10 K files,
      further attempts were made with the modified K files. As a result, the number of
      the nonpenetrated canals was reduced to 75 (4.1%). There were 7 file breakages
      and 14 accidental perforations.

PMID- 9545951
TI  - Prevalence of teaching apical patency and various instrumentation and obturation
      techniques in United States dental schools.
AB  - Maintaining an open apex beyond the apical constriction with an endodontic file
      during canal instrumentation is a concept that has been advocated by several
      authors and clinicians. To ascertain the prevalence of teaching the patency
      concept as well as various instrumentation and obturation techniques in the
      United States dental schools, a survey was conducted. Forty-eight out of a total
      of 53 dental schools (91%) responded to the survey. Results indicate that 50% of
      the schools surveyed teach the concept of patency to their undergraduates or
      graduates or both; 83% teach a step-back instrumentation technique; and 89.6%
      teach lateral condensation of gutta percha as their primary obturation technique.

PMID- 9545952
TI  - Hardness and stress-corrosion of rubber dam clamps.
AB  - Rubber dam clamps fracture infrequently during use. There are no American
      National Standards Institute or International Standards Organization standards
      for their manufacture. The purpose of this study was to measure the hardness of
      the clamps and test their resistance to a stress-corrosion test. Upper molar,
      lower molar, and premolar clamps were obtained from two manufacturers (A, B). The
      Rockwell C hardness at four sites on the bow of each clamp was then determined.
      Fresh clamps were placed on blocks corresponding to the average buccal-lingual
      dimension of the tooth on which they would be used. These blocks were then
      submerged in room temperature 5.25% sodium hypochlorite for 20 min and then
      allowed to air dry for 30 min. This was repeated 10 times. Rockwell C hardness
      values ranged from C30 to 38, with the clamps of manufacturer B being
      significantly harder. None of the clamps from manufacturer B cracked or corroded.
      When a third batch received from manufacturer A was tested in the same manner,
      none of the clamps fractured or corroded either.

PMID- 9545954
TI  - Informed consent in orthodontics.
AB  - Informed consent is a process of communication between a health care provider and
      patient that educates the patient as to the patient's needs and the potential
      solutions for those needs, and leads to the endorsement of a health care
      treatment plan. A claim of lack of informed consent may be brought by a patient
      when there is a perceived failure in the disclosure of adequate information to
      make a reasoned decision whether to consent to treatment. This article provides
      the foundation of the informed consent doctrine, delineates the essential
      elements of a lack of informed consent claim, and identifies the parties and
      their roles in the informed consent process.

PMID- 9545953
TI  - Endodontic treatment in three cases of dens invaginatus.
AB  - Three cases of dens invaginated teeth with periapical lesions are presented in
      this article. In the first case the maxillary canine was treated with
      conventional endodontic treatment. The second and third cases, in mandibular and
      maxillary central incisors respectively, were treated surgically. Six months
      postoperatively all cases appeared radiographically to be improved.

PMID- 9545955
TI  - The standard of care: the orthodontist's tort liability.

PMID- 9545956
TI  - Basic contract law.

PMID- 9545957
TI  - Bracing yourself to deal with the top 10 employment law problems.
AB  - Orthodontists face a number of legal problems in dealing with employment issues.
      Some of them are similar to those effecting other professionals, whereas other
      problems are peculiar to the practice of orthodontia. An experienced employment
      attorney offers recommendations to deal with 10 common issues confronting
      orthodontists in the workplace.

PMID- 9545958
TI  - Temporomandibular joint litigation: resolving issues of medical necessity and
      contract ambiguity.
AB  - Courts routinely award coverage for TMJ disorders under medical plans, despite
      exclusionary language and evidence that the insured failed to disclose
      preexisting treatment as required by the plan and neglected to attempt more
      conservative treatment first. Such decisions adversely affect both the health
      carrier and the plan participants. Various states have enacted legislation
      mandating coverage of TMJ; however, TMJ issues still exist and will remain a
      frequent topic for litigation until the judiciary recognizes that validating
      contract language ultimately benefits insureds as consumers and reinforces the
      integrity of the industry as a whole.

PMID- 9545959
TI  - State regulation of the practice of dentistry.
AB  - Dentistry in today's world is a highly regulated industry. It is governed
      primarily by the state, but the federal government also controls certain aspects
      of a dental practice. This article focuses on the ways in which state government
      regulates the practice of dentistry. It explains the purpose of a state licensing
      board, as well as the authority a licensing board derives from state statute-
      including the authority to take disciplinary action against practitioners who
      engage in misconduct, and the authority to promulgate rules.

PMID- 9545960
TI  - Basic insurance concepts for dentists.
AB  - Dentists cannot afford to be ignorant about insurance. Insurance is an important
      risk-management tool, minimizing the exposure for catastrophic claims and losses.
      Patient insurance is also a major source of revenue for most dental practices.

PMID- 9545961
TI  - Simple solutions.

PMID- 9545963
TI  - Medicare. Challenges ahead.

PMID- 9545964
TI  - Medicaid. Low outreach.

PMID- 9545966
TI  - Mergers. Big year for deals.

PMID- 9545965
TI  - Finance. Health care's rainmakers.

PMID- 9545967
TI  - Consumerism. Hearing voices.

PMID- 9545968
TI  - Employers. Mandate-busters.

PMID- 9545969
TI  - Management. VA performance.

PMID- 9545970
TI  - Managed care. Small-biz enrollments up.

PMID- 9545971
TI  - Mental health. Research project.

PMID- 9545972
TI  - End-of-life care. Off-site DNRs.

PMID- 9545973
TI  - Kaiser's labor pains.

PMID- 9545974
TI  - Gen-X meets Medicare. Interview by Jan Greene.

PMID- 9545975
TI  - Fields of vision. Virginia system's outreach to migrants brings health care
      directly to their camps.

PMID- 9545976
TI  - The health care 100.
AB  - They may not be the biggest health systems, the most profitable, or even those
      with the most doctors. They are the most integrated, having gone the furthest in
      building organizations that boast of geographic reach and coordinated systems of
      care. Unlike rankings that focus on size, our listing looks at health care
      enterprises that are pioneering change.

PMID- 9545977
TI  - Choice words on open access.
AB  - Drawn by rates only slightly higher than traditional HMOs, consumers have hurried
      to sign up for open-access plans. Yet what works for patients may work against
      doctors who assume the financial risks.

PMID- 9545978
TI  - Trendspotting.
AB  - All health care isn't local. To make the right strategic moves, you need to
      understand the bigger picture. A new environmental assessment from Deloitte &
      Touche and VHA, released first to Hospitals & Health Networks, sizes up the
      national scene.

PMID- 9545979
TI  - Health care costs. Twin Cities' setback.

PMID- 9545980
TI  - Consumerism. Satisfaction guaranteed.

PMID- 9545981
TI  - Access to care. Less trouble in paradise.

PMID- 9545983
TI  - Mergers. Or forever hold your peace.

PMID- 9545982
TI  - Doctor dispute. Turf's up.

PMID- 9545984
TI  - Cost control. Drain stopper on water bills.

PMID- 9545985
TI  - Hospital pulse ... September 1997.

PMID- 9545986
TI  - Child and adolescent psychiatry research remains a challenge.

PMID- 9545987
TI  - The crisis in clinical research.

PMID- 9545988
TI  - Images in psychiatry. The West Riding Pauper Lunatic Asylum.

PMID- 9545989
TI  - A new intellectual framework for psychiatry.
AB  - In an attempt to place psychiatric thinking and the training of future
      psychiatrists more centrally into the context of modern biology, the author
      outlines the beginnings of a new intellectual framework for psychiatry that
      derives from current biological thinking about the relationship of mind to brain.
      The purpose of this framework is twofold. First, it is designed to emphasize that
      the professional requirements for future psychiatrists will demand a greater
      knowledge of the structure and functioning of the brain than is currently
      available in most training programs. Second, it is designed to illustrate that
      the unique domain which psychiatry occupies within academic medicine, the
      analysis of the interaction between social and biological determinants of
      behavior, can best be studied by also having a full understanding of the
      biological components of behavior.

PMID- 9545990
TI  - Site of opioid action in the human brain: mu and kappa agonists' subjective and
      cerebral blood flow effects.
AB  - OBJECTIVE: Humans experience the subjective effects of mu and kappa opioid
      agonists differently: mu agonists produce mainly euphoria, while kappa agonists
      are more likely to produce dysphoria. This study tested the hypothesis that these
      subjective effects would be associated with anatomically distinct changes in
      regional cerebral blood flow (CBF) relative to baseline as assessed with single
      photon emission computed tomography (SPECT). METHOD: Nine nondependent opioid
      abusers participated in the study. In the first phase of the study, the
      participants were acclimated to effects of the study drugs. In the second phase
      they underwent repeat challenges with the study drugs followed by an assessment
      of CBF with use of the SPECT tracer [99mTc]HMPAO. Medications tested were the
      prototypic mu agonist hydromorphone, the mixed agonist/antagonist butorphanol
      (which has a kappa agonist component of activity), and saline placebo. RESULTS:
      Subjective effects of the drugs were distinctly different. Hydromorphone produced
      increased ratings of "good effects," while butorphanol led to more "bad effects."
      Hydromorphone significantly increased regional CBF in the anterior cingulate
      cortex, both amygdalae, and the thalamus--all structures belonging to the limbic
      system. Butorphanol caused a less distinct picture of regional CBF increases,
      mainly in the area of both temporal lobes. CONCLUSIONS: This study demonstrates
      that opioids with different subjective effects also produce statistically
      significant patterns of change in regional CBF from baseline, and the regions of
      statistical significance appear in different brain regions. In addition, these
      results demonstrate the applicability of SPECT functional neuroimaging in the
      study of medications with potential abuse liability.

PMID- 9545991
TI  - Modification of alcohol withdrawal by the A9 allele of the dopamine transporter
      gene.
AB  - OBJECTIVE: Determinants of individual vulnerability to alcohol withdrawal
      symptoms are largely unknown. Because of the substantial role of monoaminergic
      transporters in limiting time and space effects of synaptic neurotransmission,
      the dopamine transporter gene (DAT1; locus symbol: SLC6A3) was studied as a
      candidate gene possibly related to symptoms of uncomplicated alcohol withdrawal.
      METHOD: In 48 chronically intoxicated alcoholics (diagnosed according to ICD-10),
      withdrawal symptoms were examined and the presence of a variable-number tandem
      repeat in the 3' untranslated region of the DAT1 gene was determined. RESULTS:
      Withdrawal syndromes were more pronounced in the 22 patients carrying the nine
      copy repeat than in the 26 patients without this variant. Multiple regression
      analysis revealed that 4% of the variance of withdrawal was explained by this
      genotype, whereas 16% was due to the amount of alcohol the patients reported
      having consumed in the month before detoxification. CONCLUSIONS: The A9 allele of
      the dopamine transporter gene is associated with more severe effects of alcohol
      withdrawal, possibly because of modifications of the brain's capacity to
      compensate for long-term effects of ethanol on cerebral function.

PMID- 9545992
TI  - Progression from conduct disorder to antisocial personality disorder following
      treatment for adolescent substance abuse.
AB  - OBJECTIVE: This study investigated the progression from conduct disorder to
      antisocial personality disorder among individuals treated for adolescent
      substance abuse. This issue is important because of the poor outcomes observed
      among individuals with antisocial pathology after treatment for alcohol and drug
      problems. The utility of factors assessed at the time of treatment in predicting
      progression to adult antisocial personality disorder was evaluated in the context
      of developmental models of antisocial behavior. METHOD: This was a prospective
      longitudinal study of 137 substance-abusing adolescents (53 female and 84 male),
      whose average age was 15.9 years and who met the DSM-III-R criteria for conduct
      disorder. Consecutively admitted patients were recruited from two adolescent
      inpatient alcohol and drug treatment facilities. Participants were interviewed
      again 4 years after treatment. RESULTS: Four years after treatment, 61% of the
      study group met the DSM-III-R criteria for antisocial personality disorder.
      Results of a logistic regression analysis indicated that onset of deviant
      behavior at or before age 10, a greater diversity of deviant behavior, and more
      extensive pre-treatment drug use best predicted progression to antisocial
      personality disorder. At 4-year follow-up, the subjects with an antisocial
      personality disorder diagnosis exhibited more involvement with alcohol and drugs
      and poorer functioning across important life domains than the subjects without
      antisocial personality disorder. CONCLUSIONS: This study found a high rate of
      progression to antisocial personality disorder among substance-abusing
      adolescents and identified factors predictive of this progression. Careful
      assessment of conduct disorder history at the time of treatment may be valuable
      for treatment planning and intervention.

PMID- 9545993
TI  - DSM-IV substance use disorder criteria for adolescents: a critical examination
      based on a statewide school survey.
AB  - OBJECTIVE: The DSM-IV criteria for substance use disorders were incorporated into
      the 1995 Minnesota Student Survey in order to estimate the need for alcohol/drug
      treatment among adolescents in the state. This study used data from the survey to
      examine the utility of individual diagnostic criterion items, diagnostic
      categories, and diagnostic thresholds in a general adolescent population. METHOD:
      The survey was administered to ninth- and 12th-grade public school students.
      Participation was voluntary, and survey questionnaires were anonymous. The survey
      included questions about the use of substances during the past year and the
      presence of DSM-IV criterion symptoms for substance abuse and dependence. This
      study was based on responses from 74,008 students who answered these questions.
      RESULTS: Of the students who reported any substance use in the past 12 months,
      13.8% of the ninth graders and 22.7% of the 12th graders met the criteria for a
      substance abuse diagnosis, and 8.2% of the ninth graders and 10.5% of the 12th
      graders met the criteria for dependence. The presence of multiple criterion
      symptoms was strongly associated with the use of multiple drugs. Analyses of
      positive and negative predictive value, sensitivity, and specificity did not
      support the diagnostic distinction between dependence criteria and abuse
      criteria. CONCLUSIONS: A combined set of criteria, with empirically derived
      diagnostic threshold categories based on total number of symptoms, may be more
      suitable for estimates of substance use disorders and need for treatment among
      adolescents.

PMID- 9545994
TI  - Adult psychiatric status of hyperactive boys grown up.
AB  - OBJECTIVE: Numerous studies have examined the adolescent and young adult fate of
      children with attention deficit hyperactivity disorder (ADHD). In marked
      contrast, relatively little is known about the adult outcome of these children.
      There have been only two controlled, prospective studies of psychiatric status
      into adulthood. The present study was conducted to gain further understanding of
      the natural course of this common childhood condition. METHOD: This was a
      prospective follow-up of clinically diagnosed, white boys of average intelligence
      who were referred by teachers to a child psychiatric research clinic at an
      average age of 7.3 years. At a mean age of 24.1 years, 85 probands (82% of the
      childhood cohort) and 73 comparison subjects (94% of adolescent comparison
      subjects) were directly interviewed by trained clinicians who were blind to group
      status. RESULTS: Evaluations of the probands and comparison subjects indicated
      significantly higher prevalences of antisocial personality disorder (12% versus
      3%) and nonalcohol substance abuse (12% versus 4%) in the probands, whereas mood
      disorders (4% versus 4%) and anxiety disorders (2% versus 7%) were not
      significantly different. At adult follow-up, ADHD was rare, occurring in only 4%
      of the probands (no comparison subjects). CONCLUSIONS: The results of the present
      study are consistent with the authors' previously reported major findings. They
      strongly suggest that children with ADHD are at significantly higher risk for a
      specific negative course marked by antisocial and substance-related disorders.

PMID- 9545995
TI  - Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a
      randomized double-blind study. The Risperidone Study Group.
AB  - OBJECTIVE: The purpose of this study was to compare the short-term efficacy and
      safety of risperidone and clozapine in treatment-resistant chronic schizophrenic
      patients. METHOD: In a controlled double-blind, multicenter study, 86 inpatients
      with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of
      conventional neuroleptics, were randomly assigned to receive risperidone or
      clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration
      phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine
      for 1 week and then adjusted according to each patient's response. The final mean
      doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment
      efficacy and safety were evaluated with several well-known rating scales.
      RESULTS: Both risperidone and clozapine significantly reduced the severity of
      psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the
      Clinical Global Impression scale) from baseline, with no significant between
      group differences. At endpoint, 67% of the risperidone group and 65% of the
      clozapine group were clinically improved (reduction of 20% or more in total
      Positive and Negative Syndrome Scale score). Risperidone appeared to have a
      faster onset of action. In both groups extrapyramidal symptoms and other adverse
      events were few, and their severity was generally mild. Neither group showed
      evidence of a relation between drug plasma concentrations and clinical
      effectiveness. CONCLUSIONS: Risperidone was well tolerated and as effective as
      medium doses of clozapine in patients with chronic schizophrenia who had been
      resistant to or intolerant of conventional neuroleptics.

PMID- 9545996
TI  - Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of
      chlorpromazine, clozapine, and amisulpride in schizophrenic patients.
AB  - OBJECTIVE: This study examined the binding to cortical serotonin 5-HT2A receptors
      of conventional doses of the typical neuroleptic chlorpromazine in comparison
      with clozapine, the prototype atypical antipsychotic, and amisulpride, a specific
      dopamine D2-D3 blocker. METHOD: Seventeen schizophrenic patients treated with
      chlorpromazine (75-700 mg/day), four treated with clozapine (200-600 mg/day), and
      five treated with amisulpride (200-1200 mg/day) were studied. Cortical 5-HT2A
      binding was estimated by reference to the values for 14 antipsychotic-free
      schizophrenic subjects with the use of positron emission tomography and
      [18F]setoperone, a high-affinity radioligand for cortical 5-HT2A receptors.
      RESULTS: A dose-dependent decrease in the number of available cortical binding
      sites for [18F] setoperone was demonstrated in the chlorpromazine group; for the
      highest dose, there was a virtual lack of sites available for binding. A very low
      percentage of available binding sites was also observed in the clozapine-treated
      patients at all doses. This suggests a high level of 5-HT2A blockade with both
      clozapine and high doses of chlorpromazine. No significant binding of amisulpride
      to 5-HT2A receptors was detected. CONCLUSIONS: A high level of 5-HT2A receptor
      blockade does not appear specific to clozapine in comparison with high doses of
      chlorpromazine, suggesting that the distinct clinical profiles of both drugs are
      unrelated to 5-HT2A blockade itself.

PMID- 9545998
TI  - Randomized trial of general hospital and residential alternative care for
      patients with severe and persistent mental illness.
AB  - OBJECTIVE: Severe and persistent mental illnesses are often lifelong and
      characterized by intermittent exacerbations requiring hospitalization. Providing
      needed care within budgetary constraints to this largely publicly subsidized
      population requires technologies that reduce costly inpatient episodes. The
      authors report a prospective randomized trial to test the clinical effectiveness
      of a model of acute residential alternative treatment for patients with
      persistent mental illness requiring hospital-level care. METHOD: Patients
      enrolled in the Montgomery County, Md., public mental health system who
      experienced an illness exacerbation and were willing to accept voluntary
      treatment were randomly assigned to the acute psychiatric ward of a general
      hospital or a community residential alternative. There were no psychopathology
      based exclusion criteria. Treatment episode symptom improvement, satisfaction,
      discharge status, and 6-month pre- and postepisode acute care utilization,
      psychosocial functioning, and patient satisfaction were assessed. RESULTS: Of 185
      patients, 119 (64%) were successfully placed at their assigned treatment site.
      Case mix data indicated that patients treated in the hospital (N = 50) and the
      alternative (N = 69) were comparably ill. Treatment episode symptom reduction and
      patient satisfaction were comparable for the two settings. Nine (13%) of 69
      patients randomly assigned to the alternative required transfer to a hospital
      unit; two (4%) of 50 patients randomly assigned to the hospital could not be
      stabilized and required transfer to another facility. Psychosocial functioning,
      satisfaction, and acute care use in the 6 months following admission were
      comparable for patients treated in the two settings and did not differ
      significantly from functioning before the acute episode. CONCLUSIONS:
      Hospitalization is a frequent and high-cost consequence of severe mental illness.
      For patients who do not require intensive general medical intervention and are
      willing to accept voluntary treatment, the alternative program model studied
      provides outcomes comparable to those of hospital care.

PMID- 9545997
TI  - MRI study of cavum septi pellucidi in schizophrenia, affective disorder, and
      schizotypal personality disorder.
AB  - OBJECTIVE: A cavum between the septi pellucidi may reflect neurodevelopmental
      anomalies in midline structures of the brain. The authors examined cavum septi
      pellucidi in subjects with schizophrenia, affective disorder, and schizotypal
      personality disorder and in normal subjects. METHOD: Thirty schizophrenic
      patients (15 chronic, 15 first-episode), 16 patients with affective disorder
      (first-episode), 21 patients with schizotypal personality disorder, and 46 normal
      subjects were evaluated with magnetic resonance imaging. Cavum septi pellucidi
      was assessed by counting the number of 1.5-mm slices containing cavum septi
      pellucidi. RESULTS: The presence or absence of cavum septi pellucidi did not
      differentiate among groups. However, the prevalence of abnormal cavum septi
      pellucidi (i.e., cavum septi pellucidi contained on four or more slices) was
      30.4% for schizophrenic patients (36.4% for chronic, 25.0% for first-episode),
      20.0% for patients with affective disorder, 18.8% for patients with schizotypal
      personality disorder, and 10.3% for normal subjects. When the authors used the
      Nopoulos et al. criteria for rating cavum septi pellucidi, which omitted
      borderline cases with cavum septi pellucidi on three slices, the prevalence of
      abnormal cavum septi pellucidi increased to 35.0% for schizophrenia (40.0% for
      chronic, 30.0% for first-episode), 25.0% for affective disorder, 27.3% for
      schizotypal personality disorder, and 13.0% for normal subjects. There was a
      statistically significant difference in ratings between schizophrenic and normal
      subjects. CONCLUSIONS: The results suggest that alterations in midline structures
      during the course of neurodevelopment may play a role in the pathogenesis of
      schizophrenia.

PMID- 9545999
TI  - Cost comparison of state hospital and community-based care for seriously mentally
      ill adults.
AB  - OBJECTIVE: In 1989, Philadelphia began a bold experiment involving the total
      shutdown of a 500-bed state hospital. This study examines the service utilization
      and cost of treating individuals with serious mental illness in a community-based
      care system in which the state hospital was replaced with 60 extended acute care
      beds in general hospitals and 583 residential beds. METHOD: A pre-post study
      design was used to determine the utilization and cost differences before and
      after the state hospital closed for individuals with a diagnosis of schizophrenia
      who required extended psychiatric hospitalization following an acute care crisis
      episode in a general hospital. The number and cost of days spent in general and
      in extended hospital and residential treatment were compared on an episode and an
      annual basis. RESULTS: The results of this analysis showed that after the state
      hospital closed, the direct treatment cost of an episode of care increased from
      $68,446 to $78,929, and the average annual cost of care per patient increased
      from $48,631 to $66,794 because of an increase in acute care hospitalization.
      CONCLUSIONS: This study suggests that an "admission" cohort of seriously mentally
      ill patients requires an optimal mix of acute care, extended care, and
      residential beds, as well as ambulatory services, in order for cost-efficient
      care to be delivered during a crisis period. Determining the appropriate
      allocation and supply of beds in different settings is essential if community
      mental health systems are to manage the care of individuals with serious mental
      illness outside of institutional settings.

PMID- 9546000
TI  - Clinical interview skills and identification of emotional disorders in primary
      care.
AB  - OBJECTIVE: The aim of this research was to study the relationship between the
      clinical interview skills of primary care physicians and their psychodiagnostic
      ability during office visits. METHOD: Ten doctors took part in the study, and 233
      patients were assessed. The patients were seen and diagnosed by their physicians
      and interviewed afterward by a psychiatrist using the Present State Examination.
      All the interviews with the primary care physicians were recorded on videotape,
      and the Physician's Skills Observation Scale was used to analyze 10 interviews
      per doctor, five psychiatric cases and five nonpsychiatric cases. RESULTS: The
      physician's active listening (eye contact, posture, and absence of verbal
      interruptions) and ability to ask questions with psychological content were
      associated with the ability to identify the patient's emotional problems. This
      association was shown to be independent of the physician's characteristics
      (social, academic, attitudinal, and professional), the sociodemographic
      characteristics of the patients, the time spent in exploration during the office
      visit, and the severity of the emotional or somatic disorder. CONCLUSIONS: The
      findings of this research highlight the need to train primary care physicians in
      specific interview skills, in order to improve their ability to identify mental
      disorders in their practices.

PMID- 9546001
TI  - Religiosity and remission of depression in medically ill older patients.
AB  - OBJECTIVE: The effects of religious belief and activity on remission of
      depression were examined in medically ill hospitalized older patients. METHOD:
      Consecutive patients aged 60 years or over who had been admitted to medical
      inpatient services at a university medical center were screened for depressive
      symptoms. Of 111 patients scoring 16 or higher on the Center for Epidemiologic
      Studies Depression Scale, 94 were diagnosed with depressive disorder (DSM-III
      major depression or subsyndromal depression) by a psychiatrist using a structured
      psychiatric interview. After hospital discharge, depressed patients were followed
      up by telephone at 12-week intervals four times. At each follow-up contact,
      criterion symptoms were reassessed, and changes in each symptom over the interval
      since last contact were determined. The median follow-up time for 87 depressed
      patients was 47 weeks. Religious variables were examined as predictors of time to
      remission by means of a multivariate Cox model, with controls for demographic,
      physical health, psychosocial, and treatment factors. RESULTS: During the follow
      up period, 47 patients (54.0%) had remissions; the median time to remission was
      30 weeks. Intrinsic religiosity was significantly and independently related to
      time to remission, but church attendance and private religious activities were
      not. Depressed patients with higher intrinsic religiosity scores had more rapid
      remissions than patients with lower scores. CONCLUSIONS: In this study, greater
      intrinsic religiosity independently predicted shorter time to remission. To the
      authors' knowledge, this is the first report in which religiosity has been
      examined as a predictor of outcome of depressive disorder.

PMID- 9546002
TI  - Reduction by paroxetine of suicidal behavior in patients with repeated suicide
      attempts but not major depression.
AB  - OBJECTIVE: Suicidal behavior has been associated with reduced central
      serotonergic function. Because selective serotonin reuptake inhibitors (SSRIs)
      enhance serotonergic function, the authors studied the efficacy of an SSRI,
      paroxetine, in the prevention of recurrent suicidal behavior. METHOD: They
      conducted a 1-year double-blind study comparing paroxetine (40 mg/day) and
      placebo in 91 patients who had recently attempted suicide for at least a second
      time. None of the patients had experienced a major depressive episode or had any
      other major DSM-III-R axis I diagnoses. At least one cluster B personality
      disorder was present in 74 patients. RESULTS: With adjustment for the number of
      previous suicide attempts, paroxetine showed significant efficacy in the
      prevention of recurrent suicidal behavior. Among the patients who had attempted
      suicide fewer than five times, 12 (36%) in the placebo group (N = 33) and five
      (17%) in the paroxetine group (N = 30) made a subsequent suicide attempt.
      Paroxetine was also significantly more effective in patients who met fewer than
      15 criteria for cluster B personality disorders than in those who met more than
      15 criteria. Overall, paroxetine was not significantly different from placebo in
      its effect on depressive mood, hopelessness, and anger. However, the data suggest
      that paroxetine may have some temporary effect in reducing anger. CONCLUSIONS:
      This study indicates that enhancing serotonergic function with an SSRI may reduce
      suicidal behavior in a subgroup of patients who have attempted suicide more than
      once but who do not suffer from major depression.

PMID- 9546003
TI  - Does fluoxetine augment the inpatient treatment of anorexia nervosa?
AB  - OBJECTIVE: While pharmacological interventions are of established utility in
      bulimia nervosa, medications have no clear role in the treatment of anorexia
      nervosa. Because patients with anorexia nervosa frequently exhibit mood
      disturbances and symptoms of obsessive-compulsive disorder, the authors tested
      the utility of fluoxetine in the treatment of women participating in an inpatient
      program for anorexia nervosa. METHOD: The authors conducted a randomized, placebo
      controlled, double-blind, 7-week study of fluoxetine at a target daily dose of 60
      mg in 31 women with anorexia nervosa receiving treatment for their eating
      disorder on a clinical research unit. Body weight and measures of eating behavior
      and psychological state were obtained at baseline and at termination. RESULTS:
      There were no significant differences in clinical outcome on any measure between
      patients receiving fluoxetine and patients receiving placebo. CONCLUSIONS:
      Fluoxetine does not appear to add significant benefit to the inpatient treatment
      of anorexia nervosa.

PMID- 9546004
TI  - Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects.
AB  - OBJECTIVE: The authors' goal was to use structured clinical interviews to
      characterize the type and frequency of mental illness in adults with fetal
      alcohol syndrome or fetal alcohol effects. METHOD: Twenty-five subjects who met
      criteria for fetal alcohol syndrome or fetal alcohol effects, who were older than
      18 years old, and who had an IQ of greater than 70 were interviewed with the
      Structured Clinical Interview for DSM-IV Axis I Disorders and the Structured
      Clinical Interview for DSM-III-R Personality Disorders. RESULTS: Eighteen of the
      25 subjects had received psychiatric treatment. The most common axis I disorders
      were alcohol or drug dependence (15 subjects), depression (11 subjects), and
      psychotic disorders (10 subjects). The most common axis II disorders were
      avoidant (six subjects), antisocial (four subjects), and dependent (three
      subjects) personality disorders. CONCLUSIONS: This study suggests that adults
      with fetal alcohol syndrome or fetal alcohol effects suffer from substantial
      mental illness.

PMID- 9546005
TI  - Higher prevalence of obsessive-compulsive symptoms in patients with blepharospasm
      than in patients with hemifacial spasm.
AB  - OBJECTIVE: The prevalences of obsessive-compulsive symptoms in patients suffering
      from blepharospasm and in those with hemifacial spasm were determined. The two
      conditions have similar symptoms, but only blepharospasm is etiologically linked
      to basal ganglia dysfunction. METHOD: After being interviewed with the Structured
      Clinical Interview for DSM-III-R, 13 patients with blepharospasm and 13 with
      hemifacial spasm completed the SCL-90-R and the Hamburg Obsession/Compulsion
      Inventory-Short Form. RESULTS: Patients in the blepharospasm group had
      significantly more obsessive-compulsive symptoms, as indicated by higher scores
      on the Hamburg Obsession/Compulsion Inventory-Short Form, than the patients with
      hemifacial spasm. SCL-90-R scores were in the normal range for nine and eight
      categories, respectively (out of nine). CONCLUSIONS: The findings provide
      additional support for the hypothesis that obsessive-compulsive symptoms are
      related to basal ganglia dysfunction.

PMID- 9546006
TI  - Defense mechanism changes in successfully treated patients with obsessive
      compulsive disorder.
AB  - OBJECTIVE: Changes in defense mechanisms after treatment of patients with
      obsessive-compulsive disorder (OCD) were measured by using an established rating
      scale. METHOD: Before and after 7-week group behavior therapy, 17 patients with
      DSM-III-R OCD were assessed with the Defense Style Questionnaire, Yale-Brown
      Obsessive Compulsive Scale, and Beck Depression Inventory. RESULTS: After
      behavior therapy the patients evidenced significant decreases in Yale-Brown
      Obsessive Compulsive Scale scores and significant increases in the use of more
      adaptive defense mechanisms. There were no significant changes in three
      maladaptive defense mechanism categories. The improvement in adaptive defenses
      was independently linked to improvement both in OCD and in depression.
      CONCLUSIONS: Personality as defined by defense mechanisms may be more amenable to
      brief behavioral treatment than previously thought. The permanence of these
      changes must be further assessed.

PMID- 9546007
TI  - Retrospective review of treatment outcome for 63 patients with trichotillomania.
AB  - OBJECTIVE: The authors' goal was to assess naturalistic treatment outcome in
      trichotillomania. METHOD: Sixty-three patients who had been treated in a
      specialty clinic for trichotillomania over a period of 6 years were contacted.
      The patients were given paper-and-pencil instruments that assessed current
      severity of hairpulling, depression, anxiety, self-esteem, and psychosocial
      functioning. RESULTS: Significant mean improvement was found on measures of
      hairpulling, depression, anxiety, self-esteem, and psychosocial functioning.
      Improvement in hairpulling was associated with greater depression at the time of
      their index clinic evaluation as well as more improvement in depression after
      treatment. CONCLUSIONS: State-of-the-art behavioral and pharmacological
      treatments offer substantial clinical benefit to patients with trichotillomania,
      both in hairpulling symptoms and ancillary measures of functioning.

PMID- 9546008
TI  - PTSD symptoms in Bosnian refugees 1 year after resettlement in the United States.
AB  - OBJECTIVE: The authors' goal was to describe the characteristics of posttraumatic
      stress disorder (PTSD) symptoms on resettlement in the United States and at 1
      year follow-up among Bosnian refugees as well as possible factors affecting the
      PTSD symptom profile among these refugees. METHOD: They used standardized
      instruments to assess 34 Bosnian refugees for PTSD at resettlement in the United
      States and 1 year later. RESULTS: Fifteen of the refugees were diagnosed with
      PTSD at 1-year follow-up, compared with 25 at initial assessment. The average
      PTSD severity score at follow-up was 12.5, compared with 20.6 at initial
      assessment. At 1-year follow-up, 25 of the refugees experienced a decrease in
      severity of PTSD symptoms, one remained the same, and eight experienced an
      increase in severity. Older refugees were significantly more likely to have PTSD
      than younger refugees, and older refugees had more severe symptoms. CONCLUSIONS:
      The level of PTSD diagnosis and symptoms in Bosnian refugees remained substantial
      1 year after their resettlement in the United States, although there were notable
      overall decreases. Older refugees appeared to be at greater risk.

PMID- 9546010
TI  - Interaction of fluoxetine and valproic acid.

PMID- 9546009
TI  - Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curacao
      Extrapyramidal Syndromes Study III.
AB  - OBJECTIVE: The authors examined the association between three lifetime medication
      variables (cumulative amount of neuroleptics, number of interruptions in
      neuroleptic treatment, cumulative amount of anticholinergics) and the occurrence
      and severity of tardive dyskinesia. METHOD: The study was conducted in the only
      psychiatric hospital of a well-defined catchment area (the Netherlands Antilles).
      For all patients who had a history of taking neuroleptics for at least 3 months
      and were currently using neuroleptics (N = 133, mean age = 51.5 years), the
      presence and severity of tardive dyskinesia were measured with the Abnormal
      Involuntary Movement Scale. RESULTS: Of the three lifetime medication variables,
      only the number of neuroleptic interruptions was significantly related to tardive
      dyskinesia. The risk of tardive dyskinesia was three times as great for patients
      with more than two neuroleptic interruptions as for patients with two or fewer
      interruptions. CONCLUSIONS: This finding supports the schizophrenia protocol of
      long-term neuroleptic treatment rather than targeted or intermittent neuroleptic
      treatment.

PMID- 9546011
TI  - Ethics in forensic psychiatry.

PMID- 9546012
TI  - Utilization management criteria for psychiatry.

PMID- 9546013
TI  - Squamous cells as predictors of bacterial contamination in urine samples.
AB  - STUDY OBJECTIVE: To determine whether squamous cells in urine indicate bacterial
      contamination. METHODS: We prospectively studied 105 consecutive women who
      presented to the emergency department with symptoms suggestive of a urinary tract
      infection. Two urine samples were collected from each woman, a midstream clean
      catch (MSCC) sample and a catheterized (CATH) sample. Microscopic urinalyses to
      assess for squamous cells and urine cultures to assess for bacterial
      contamination were performed on all samples. Bacterial contamination was defined
      as growth of fewer than 10,000 colonies of a single species per milliliter or
      growth of three or more species of commensal bacteria (mixed flora) in a urine
      sample. RESULTS: Squamous cells were found in 99 of 105 CATH samples (94%);
      however, no CATH samples had bacterial contamination. Squamous cells were found
      in 101 of 105 MSCC samples (96%); however, only 22 MSCC samples (21%) had
      bacterial contamination. CONCLUSION: The presence of squamous cells in CATH urine
      samples obtained from women is not indicative of bacterial contamination. The
      presence of squamous cells in MSCC urine samples obtained from women also is not
      a good indicator, with an overall predictive value for bacterial contamination of
      21%.

PMID- 9546014
TI  - Comparison of arterial and venous blood gas values in the initial emergency
      department evaluation of patients with diabetic ketoacidosis.
AB  - STUDY OBJECTIVE: To determine whether venous blood gas values can replace
      arterial gas values in the initial emergency department evaluation of patients
      with suspected diabetic ketoacidosis. METHODS: This prospective comparison was
      performed in an adult university teaching hospital ED. Samples for arterial and
      venous blood gas analysis were obtained during initial ED evaluations. The venous
      gas samples were collected with samples for other blood tests at the time of
      intravenous line insertion. Both arterial and venous samples were obtained before
      the initiation of treatment. RESULT: Data from 44 episodes of diabetic
      ketoacidosis in 38 patients were analyzed. Laboratory findings of those patients
      with diabetic ketoacidosis were as follows (mean +/- SD): arterial pH, 7.20 +/-
      14; venous pH, 7.17 +/- 13; serum glucose, 33.8 +/- 16 mmol/L (609 +/- 288
      mg/dL); arterial HCO3-, 11.0 +/- 6.0 mmol; venous HCO3-, 12.8 +/- 5.5 mmol/L;
      serum CO2, 11.8 +/- 5.0 mmol/L; and anion gap, 26.7 +/- 7.6 mmol/L. The mean
      difference between arterial and venous pH values was 0.03 (range 0.0 to 0.11).
      Arterial and venous pH results (r = .9689) and arterial and venous HCO3- results
      (r = .9543) were highly correlated and showed a high measure of agreement.
      CONCLUSION: Venous blood gas measurements accurately demonstrate the degree of
      acidosis of adult ED patients presenting with diabetic ketoacidosis.

PMID- 9546015
TI  - Organ procurement in an urban level I emergency department.
AB  - STUDY OBJECTIVE: To determine whether an intensive educational campaign of
      emergency department personnel on the organ donor and procurement process would
      result in both increased organ donor referrals and organs procured. METHODS: A
      retrospective review of the performance of an urban teaching ED in identifying
      and referring potential organ donor candidates was performed. Subsequently an
      intensive educational campaign of all ED staff, in conjunction with the Regional
      Organ Procurement Agency of Southern California (ROPA), was initiated. Physicians
      and nurses were educated about the procurement process, and a ROPA representative
      was on call 24 hours a day to assist in this process. The need for aggressive
      resuscitation and vital sign maintenance in potential donors as a strategy to
      promote organ recovery was emphasized. Reeducation by ROPA occurred every 2 to 3
      months. The identification and referral rates were then retrospectively reviewed
      to evaluate any improvement. RESULTS: In 1994 the initial referral rate of
      potential organ donors from the ED was 30% (3 of 10) resulting in no organs
      procured. After the intervention the referral rate increased to 100% (25 of 25)
      in 1995 (P < .0001). The number of actual donors procured was 0 in 1994, 5 in
      1995, and 9 in 1996. The increased ED referrals resulted in 14 and 32 organs
      procured in 1995 and 1996, respectively. CONCLUSION: Emergency physicians are in
      a unique position as first caregivers to interact with both potential donors and
      their families. With intensive education of ED staff, proper identification and
      referral, as well as timely intervention by organ procurement representatives,
      the consent and donation rate of organs for transplantation can be increased and
      maintained.

PMID- 9546016
TI  - Effects of adding links to "the chain of survival" for prehospital cardiac
      arrest: a contrast in outcomes in 1975 and 1995 at a single institution.
AB  - STUDY OBJECTIVE: The concept of a "chain of survival" to improve outcome from
      prehospital cardiac arrest has been defined and promulgated over the last two
      decades. The purpose of this study was to compare outcomes of prehospital cardiac
      arrest in 1975 and 1995 at a single institution. METHODS: This longitudinal,
      before-after study compares published data collected at our municipal, tertiary
      care in 1974-1975 with data collected prospectively in 1995. The 1975 study group
      served as control subjects (n = 120). We enrolled an equal number of consecutive
      patients who met inclusion criteria in the 1995 cohort (consecutive patients who
      experienced prehospital arrest and who received prehospital Advanced Cardiac Life
      Support (ACLS) measures during the two study periods). Patients younger than 18
      years or with posttraumatic arrest were excluded. Between 1975 and 1995 the
      following "links" in the "chain of survival" were added to the prehospital care
      system: (1) 911 access and dispatch, (2) paramedic endotracheal intubation, (3)
      EMT automated defibrillation, (4) standing out-of-hospital orders before hospital
      radiotelemetry contact, and (5) introduction of American Heart Association ACLS
      algorithms. RESULTS: The following significant differences (chi 2) were observed
      between the study periods: prevalence of ventricular fibrillation or tachycardia
      (42% in 1975 versus 28% in 1995, P = .021), prevalence of asystole or pulseless
      electrical activity as the first documented rhythm (58% versus 72%, P = .021),
      survival to hospital discharge (22% versus 9%, P = .007), and percent of
      survivors of ventricular fibrillation or tachycardia (30% versus 0%, P = .004).
      Eighty-six percent of the 1995 cohort had advanced chronic disease and 29%
      experienced cardiopulmonary arrest in a nursing home. CONCLUSION: Survival
      decreased dramatically during the 20-year study period. This may be because of
      the high incidence of chronic disease, the greater frequency of asystole and
      pulseless electrical activity, and the inclusion of patients with "end-of-life"
      arrests in which ACLS protocol was initiated in the 1995 cohort. The patient
      population in which ACLS is initiated is the weakest link in the "chain of
      survival."

PMID- 9546017
TI  - Race and survival after out-of-hospital cardiac arrest in a suburban community.
AB  - STUDY OBJECTIVE: To determine whether race, when controlled for income, is an
      independent predictor of survival to hospital discharge after out-of-hospital
      cardiac arrest (OHCA). METHODS: Prospective OHCA data were collected over 4 years
      (1991-1994) from a convenience sample of OHCA patients transported to nine
      hospitals in three suburban counties. Race was determined from hospital and vital
      statistics records. The average household income was identified from ZIP codes
      and used as a marker of socioeconomic status. Demographic data and known
      predictors of survival were compared between blacks and whites. A logistic
      regression analysis was used to assess the association between race, income, and
      survival. RESULTS: Of the 1,690 patients, 223 (13%) were blacks and 1,467 (87%)
      were whites. Average household income was less for blacks than for whites
      ($40,225 versus $46,193; P < .001), but both populations were affluent by
      national standards (national percentile ranks were 73% and 88%, respectively).
      The populations were no different in percentage of witnessed arrests (57% versus
      61%; P = .465). Blacks were younger (mean +/- SD, 62 +/- 16 versus 68 +/- 15
      years; P < .001); less frequently received bystander CPR (11% versus 20%; P =
      .002); less often had ventricular tachycardia or ventricular fibrillation (37%
      versus 50%; P < .001); and had a shorter advanced life support call-response
      interval (median, 4 versus 6 minutes; P < .001). The odds ratio for survival
      (white/black) was .931 (95% confidence interval, .446 to 1.945). CONCLUSION: Race
      was not found to predict adverse OHCA outcomes in this affluent population.

PMID- 9546018
TI  - Synchronization of timepieces to the atomic clock in an urban emergency medical
      services system.
AB  - STUDY OBJECTIVE: Erroneous time documentation of emergency treatment caused by
      the variation in the accuracy of timepieces has profound medical, medicolegal,
      and research consequences. The purpose of this study was to confirm the variation
      of critical timepiece settings in an urban emergency care system noted in
      previous studies and to implement and monitor the results of a prospective
      program to improve time synchronization. METHODS: Timepieces (n = 393) used by
      firefighters, paramedics, and emergency physicians and nurses were randomly
      sampled immediately before and at two time intervals (1 and 4 months) after
      attempted synchronization to the US atomic clock standard. The setting on each
      timepiece was compared with the atomic clock. From the data, a mathematical
      simulation estimated the number of time-related documentation errors that would
      occur in 2,500 simulated cardiac arrest cases using timepieces with accuracy
      similar to those found in the EMS system before and after attempted
      synchronization. RESULTS: Before attempted synchronization, the timepieces had a
      mean error of 2.0 (95% confidence interval 1.8 to 2.3) minutes. One month after
      attempted synchronization, the mean error decreased significantly to .9(.8 to
      1.1) minute. However, it increased to 1.7 (1.5 to 1.9) minutes within 4 months.
      Mathematical simulation before attempted synchronization predicted that 93% of
      cardiac arrest cases would contain a documentation error of 2 minutes or more and
      that 41% of cases would contain a documentation error of 5 minutes or more.
      Attempted synchronization cut the 2-minute documentation error rate in half and
      reduced the 5-minute documentation error rate by three fourths. However, the
      error rates were predicted to return to baseline 4 months after attempted
      synchronization. CONCLUSION: Emergency medical timepieces are often inaccurate,
      making it difficult to reconstruct events for medical, medicolegal, or research
      purposes. Community synchronization of timepieces to the atomic clock can reduce
      the problem significantly, but the effects of a one-time attempted
      synchronization event are short-lived.

PMID- 9546019
TI  - Failure of the mandatory domestic violence reporting law to increase medical
      facility referral to police.
AB  - STUDY OBJECTIVE: To assess the effect of California's 1994 mandatory domestic
      violence reporting law on Los Angeles Sheriff's Department dispatches to medical
      facilities for domestic violence incidents. METHODS: This ecological time-trend
      study analyzed data from the Los Angeles Sheriff's Department for the period
      January 1, 1993, to December 31, 1995. All 26,051 dispatches for domestic
      violence offenses during the study period were analyzed. The outcome measures
      were changes in biweekly department dispatches for domestic violence offenses
      resulting from the implementation of the mandatory domestic violence reporting
      law adjusted for seasonal variation and the Simpson/Goldman murders. RESULTS: The
      percentage of biweekly dispatches to medical facilities for domestic violence
      offenses did not increase in response to the law (beta = -.0072, P = .095). Total
      domestic violence dispatches increased significantly after the Simpson/Goldman
      murders but not after passage of the law (beta = 82.7, P < .0001 versus beta = 
      10.1, P = .2205). CONCLUSION: The mandatory domestic violence reporting law in
      California did not increase medical personnel reporting of domestic violence
      situations to the Sheriff's Department during the 2 years after its
      implementation.

PMID- 9546020
TI  - Comparison of domestic violence screening methods: a pilot study.
AB  - STUDY OBJECTIVE: Previous studies have indicated a number of barriers to
      screening for domestic violence (DV) in an emergency department setting. These
      barriers result in inconsistencies which determine who is screened as well as the
      content and quality of the information obtained, and if uncontrolled they are
      likely to affect measurements of DV incidence in ED populations. The objectives
      of this project were to design a screening tool that circumvented these barriers
      and sources of error; to assess whether such an alternative method of screening
      for DV was acceptable to our patients; and to determine whether the alternative
      and traditional methods of screening for DV would yield comparable results. Our
      hypotheses were that the alternative screening tool would be acceptable to our
      patients and that no significant differences would be found between the two
      methods. METHODS: The study took place in a rural, university-affiliated ED with
      approximately 36,000 annual patient visits. The study population consisted of 186
      women older than 18 years of age who were treated by one designated physician.
      Approximately half of these subjects were screened for DV in a face-to-face
      interview. The other half listened to a tape-recorded questionnaire and recorded
      their responses on a coded answer sheet. RESULTS: There were 175 completed
      screenings. The average age of all respondents was 34 years, and 90 (51%)
      indicated a cumulative lifetime experience of DV of some sort. Overall, 3% of the
      respondents indicated they were in the ED for injuries received as a result of
      DV. No significant differences were found between the two methods of screening
      for DV on any measurement, including refusals. No problems hearing the tape or
      understanding the instructions were reported. CONCLUSION: These results indicate
      that the alternative method of employing a recorded questionnaire was no less
      effective than the best efforts of a designated and conscientious physician. As a
      means of quickly assessing the prevalence of DV in an ED setting, we find much to
      recommend such an approach.

PMID- 9546021
TI  - Emergency department-based study of risk factors for acute injury from domestic
      violence against women.
AB  - STUDY OBJECTIVES: To evaluate the associations between selected socioeconomic
      risk factors and acute injury from domestic violence against women. METHODS: We
      conducted a preliminary matched case-control study to measure the association of
      selected predictor variables with acute injury from domestic, violence against
      women. Patients identified as cases were Hispanic or white female emergency
      department patients, 16 to 65 years of age, with acute injury sustained from
      physical assault by an intimate male partner. Cases were selected for inclusion
      in the study if they reported or admitted acute physical assault by their male
      partners. Controls were selected from non-case female ED patients so as to
      represent the base population of the cases and enhance comparability. Two
      controls were matched to each case. The socioeconomic predictor variables
      examined were the education level, employment status, history of alcohol abuse,
      and history of drug abuse of the male partner and the education level and
      cohabitation status of the female partner. RESULTS: Forty-six cases were
      identified and included in the study. The age range was 16 to 51 years (mean, 33
      years). There were 26 (57%) Hispanic and 20 (43%) white cases. The strongest
      predictor for acute injury from domestic violence in these patients was a history
      of alcohol abuse by the male partner, as reported by the female partner (odds
      ratio, 12.9). The remaining predictor variables were weakly associated or not
      associated with domestic violence. One half of the cases stated that their male
      partners were intoxicated with alcohol at the time of assault. CONCLUSION: Of the
      socioeconomic variables examined in this preliminary study, a history of alcohol
      abuse by the male partner, as reported by the female partner, was the strongest
      predictor for acute injury from domestic violence. A large-scale, multicenter, ED
      based study is needed to clarify the relation between alcohol abuse, other
      socioeconomic factors, and acute physical assaults against women by their
      intimate male partners.

PMID- 9546022
TI  - Evaluation of orthotopic liver transplant recipients presenting to the emergency
      department.
AB  - Improved survival rates and more centers performing liver transplantation have
      resulted in increasing numbers of liver transplant recipients presenting to
      emergency departments. This article familiarizes emergency physicians with
      orthotopic liver transplantation and complications that cause liver transplant
      recipients to visit EDs.

PMID- 9546023
TI  - National Highway Traffic Safety Administration (NHTSA) notes. 1996 Motor Vehicle
      Occupant Safety Survey.

PMID- 9546024
TI  - National Highway Traffic Safety Administration (NHTSA) notes. Commentary: and who
      is my neighbor?

PMID- 9546025
TI  - Pediatric death and fluoride-containing wheel cleaner.

PMID- 9546026
TI  - Ammonium bifluoride causes another pediatric death.

PMID- 9546027
TI  - Pulse oximetry gap in carbon monoxide poisoning.

PMID- 9546029
TI  - Health care guidelines for cruise ship medical facilities. American College of
      Emergency Physicians.

PMID- 9546028
TI  - Regional intravenous infusion of calcium gluconate for hydrofluoric acid burns of
      the upper extremity.

PMID- 9546030
TI  - Familial dysautonomia: a 47-year perspective. How technology confirms clinical
      acumen.
AB  - A historical perspective of familial dysautonomia is presented, highlighting the
      early contributions of Dr. Joseph Dancis. As further investigations proceeded,
      his original observations have withstood the test of time and may contribute to
      determining the molecular abnormality in this rare genetic disorder. Dr. Dancis's
      work in this area serves as a model of how observations based on clinical acumen
      and critical thinking can be verified by future technological advances.

PMID- 9546031
TI  - Nutritional studies of the embryo during early organogenesis with normal embryos
      and embryos exhibiting yolk sac dysfunction.
AB  - In 1961 we reported that heterologous kidney antiserum when injected into
      pregnant rats resulted in wide spectrum of congenital malformations. Further
      studies identified that it was the IgG component of the antiserum that was
      teratogenic and that complement was not necessary to produce the teratogenic
      effect. Labeled antibody studies demonstrated that the kidney antiserum localized
      in the kidney and in the visceral yolk sac (VYS) and parietal yolk sac placentas.
      Preparation of yolk sac (YS) antiserum proved to be more potent than the kidney
      antiserum. Adsorption studies with VYS and parietal yolk sac antiserum revealed
      that the site of the teratogenic process was located in the VYS. In vitro embryo
      culture experiments demonstrated that direct injection of the teratogenic
      antibody into the amniotic or YS cavity did not injure the embryo, thus
      indicating that the teratogenic antibody had to come in contact with the
      absorptive surface of the VYS. Collaboration with Dr. John Lloyd demonstrated
      that teratogenic antibody interfered with the process of pinocytosis and the
      delivery of amino acids (AA) to the developing embryo. Our studies into the
      nature of the source of AA for the embryo indicated that in some instances > 95%
      of the AA present in the developing embryo were derived from maternal proteins
      and the remainder from free AA in the maternal serum. We also demonstrated that
      embryonic methionine was derived primarily from the digestion of maternal serum
      proteins but that more of the methionine was diverted from the synthesis of
      embryonic proteins, supporting the view that it has important functions other
      than the synthesis of proteins. All these studies focus on the role of the YS in
      human development and whether human YS dysfunction may play a role in the
      pathogenesis of congenital malformations. Further studies on the delivery of AA
      to the embryo are warranted to determine whether certain AA are in short supply
      in maternal serum and place the embryo at risk if nutritional alterations in the
      maternal environment occurs. Furthermore, the YS may be an organ whose role might
      offer opportunities for pregnancy control.

PMID- 9546032
TI  - Maple syrup urine disease: it has come a long way.
AB  - Maple syrup urine disease (MSUD) was first described in 1954 by Menkes et al. as
      a progressive neurologic degenerative disorder. In 1960, Dancis et al.
      established that the metabolic block in MSUD is at the decarboxylation of
      branched-chain alpha-ketoacids derived from leucine, isoleucine, and valine. The
      multienzyme complex affected in MSUD, the mitrochondrial branched-chain alpha
      ketoacid (BCKD) dehydrogenase complex was purified in 1978 to homogeneity in
      Reed's laboratory. This led to the later cloning of cDNAs and genes for subunits
      of the human BCKD complex. Genetic heterogeneity in MSUD is now explained by the
      various mutations that occur in the E1 alpha, E1 beta, E2, and E3 loci of the
      BCKD complex. Recently, we found that bacterial chaperonins GroEL and GroES
      promote folding and assembly of E1 decarboxylase component of the BCKD complex in
      Escherichia coli. Pulse-chase labeling in this system showed that a subset of E1
      alpha mutations, notably the homozygous Y393N-alpha in Mennonite MSUD patients,
      impedes the assembly of the mutant E1 alpha subunit with normal E1 beta. The
      assembly defect is associated with a rapid degradation of the normal E1 beta
      subunit in MSUD cells. Retrovirus-mediated transduction of lymphoblasts from a
      Mennonite MSUD patient with a normal E1 alpha cDNA resulted in a complete
      restoration of BCKD activity. This was accompanied by a stabilization of the
      normal E1 beta subunit through assembly with recombinant E1 alpha. The results
      demonstrated the feasibility of stable correction of E1 alpha-deficient (type IA)
      MSUD and provided a basis for the development of gene therapy.

PMID- 9546033
TI  - Genetic analysis of iron uptake in the yeast Saccharomyces cerevisiae.
AB  - OBJECTIVE: We used the methods of yeast genetics to identify genes involved in
      acquisition of iron by eukaryotic cells. METHODS: Mutants were identified with
      defects in cellular iron uptake. These were organized into an upstream group and
      a downstream group. The upstream group was involved in the delivery of copper to
      the multicopper oxidase FET3. Mutants of this group were characterized by
      defective iron uptake that could be corrected by exposure of the cells to large
      amounts of copper. The downstream group was more directly involved in iron
      uptake. Mutant phenotypes from these genes could not be corrected by copper
      exposure. RESULTS: Genes in the upstream group encoded the regulator of copper
      transport, MAC1, and two copper transporters, CTR1 and CCC2. Genes in the
      downstream group encoded the multicopper oxidase FET3 and its partner the iron
      permease FTR1. In addition, the downstream genes encoded the surface reductases
      FRE1 and FRE2 and the iron regulatory protein AFT1. CONCLUSIONS: The iron and
      copper uptake processes in yeast intersect because the FET3 gene encodes a
      multicopper oxidase that is required for iron transport. In human beings, an
      analogous function may be served by ceruloplasmin, a multicopper oxidase with a
      role in iron homeostasis.

PMID- 9546034
TI  - Mechanisms of cerebral injury in perinatal asphyxia and strategies for
      prevention.
AB  - We have investigated the mechanisms of hypoxic brain cell injury in the immature
      animal by examining (1) the role of excitatory amino acid neurotransmitter
      receptors, (2) the receptor-mediated increase in intracellular Ca2+, and (3) the
      generation of oxygen free radicals. We examined the effect of brain tissue
      hypoxia on the NMDA receptor-ion channel complex including the glutamate, Mg2+,
      spermine, CPP, and the non-NMDA receptor kainate sites. Brain tissue hypoxia
      resulted in modification of the NMDA receptor ion channel and its modulatory
      sites. Hypoxia increased the affinity of both the ion channel and the glutamate
      recognition site. Pretreatment of animals with the glutamate antagonist CPP
      prevented hypoxia-induced modification of the channel. Similarly, pretreatment of
      animals with Mg2+, a blocker of the NMDA receptor ion channel, prevented the
      hypoxia-induced modification of the receptor. In addition, an increased agonist
      dependent entry of Ca2+ into synaptosomes was observed in hypoxic animals
      compared with normoxic animals. Increased free radical generation in the cerebral
      cortex during hypoxia was demonstrated using spin labeling technique and electron
      spin resonance spectroscopy. We conclude that hypoxia-induced modification of the
      NMDA receptor-ion channel complex leads to increased intracellular Ca2+
      potentiating free radical generation and resulting in hypoxic cell injury.

PMID- 9546035
TI  - Transport and endogenous release of vitamin B12 in the dually perfused human
      placenta.
AB  - The kinetics for vitamin B12, cobalamin (Cbl), transfer across the human
      placenta, and the retention of the endogenous Cbl and its release into the
      maternal and fetal compartments were investigated in a dually perfused human term
      placenta in vitro. After 4 hours of perfusion following a single bolus injection
      (peak maternal perfusate 94 fmol/ml) of 57Co-Cbl into the maternal reservoir, the
      maternal [57Co-Cbl] rapidly decreased whereas the fetal [57Co-Cbl] was only 9% of
      the final maternal [57Co-Cbl]. Even though there was a limited transfer of 57Co
      Cbl to the fetus, the placenta rapidly accumulated Cbl. At 4 hours, 18% of the
      initial 57Co-Cbl dose was in the placenta; only 3% of the initial dose was in the
      fetal perfusate. Also after 4 hours, [57Co-Cbl] was bound > 95% to transcobalamin
      (TC)I/III-like proteins in the maternal perfusate, whereas Cbl was bound to
      TCI/III- and TCII-like proteins with some free in the fetal perfusate. In the
      cytosol, > 95% of the [57Co-Cbl] was bound (80% to TCII-like and 19% to TCI/III
      like proteins). When no exogenous Cbl was added, total endogenous [Cbl] in the
      maternal circulation increased with time during 8 hours of perfusion at a rate of
      0.25 +/- 0.12 pmol/gm per hour. Only 2% of this Cbl was free, whereas 98% was
      bound to specific binding proteins. Neither plateau values nor equilibration with
      the fetal side were noted. In the fetal circulation, there was a release of Cbl
      at a rate of 0.015 +/- 0.003 pmol/gm per hour, which was 99.99% bound. Thus the
      human placenta rapidly concentrates Cbl in the perfused lobule with little
      distribution of Cbl to nonperfused areas. Therefore, the human placenta modulates
      the asymmetric transfer of vitamin B12 on the basis of release of specific Cbl
      binding proteins (TCI/III- and TCII-like) into the maternal and fetal perfusates.

PMID- 9546036
TI  - Aging, changes in the cardiovascular system, and responses to stress.
AB  - I have presented a picture of cardiovascular aging that resembles the situation
      with vision, where in the absence of actual disease, near vision changes with age
      and cataracts appear with age but after these are corrected, vision remains
      markedly unchanged with age. For the undiseased heart, intrinsic cardiac muscle
      function and the inotropic response to nonsympathetic mediators, along with
      coronary perfusion, are well maintained with age. There are, however, some
      changes that do occur with age. Cellular hypertrophy occurs, both because of cell
      drop out and because of some chamber hypertrophy secondary to increased impedance
      to left ventricular ejection. As a result of the hypertrophy, there is some
      prolongation of systole secondary to delayed relaxation. This is typical of what
      occurs in hypertension induced hypertrophy as well. These age-related changes are
      of critical importance and are the background for the entire discussion of the
      interplay between hypertension and disease. The large arteries do in fact stiffen
      with age. Thus, even without hypertension, there is an age-related increased
      impedance to ejection, a greater systolic load, a lower coronary perfusion
      pressure, and an increased pulse wave velocity. Added to this is the failure of
      the entire beta-sympathetic system to respond as well in the elderly as in the
      younger individuals with a resultant decrease in the vasodilating response. Both
      the chronotropic and inotropic response to sympathetic mediation is diminished so
      that states that put sudden loads on the left ventricle, such as accelerated
      hypertension or myocardial infarction, have more severe results in the elderly.
      Also acute hypertension may produce less hypertrophy in the elderly and therefore
      place more hemodynamic stress on the left ventricle than in young adults.

PMID- 9546037
TI  - Renal disease and renal artery stenosis in the elderly.

PMID- 9546038
TI  - Uncommon forms of secondary hypertension in older patients.

PMID- 9546039
TI  - Quality of life during antihypertensive treatment. Lessons from the Systolic
      Hypertension in the Elderly Program.

PMID- 9546040
TI  - Individualized selection of antihypertensive drug therapy for older patients.

PMID- 9546041
TI  - Cloning and sequence analysis of the cDNA encoding the elongation factor-1 beta
      of Dictyostelium discoideum.
AB  - A cDNA encoding elongation factor-1 beta (DdEF-1 beta) for protein synthesis was
      isolated from Dictyostlium discoideum cells by the differential display (DD)
      method. The DdEF-1 beta cDNA sequence with a length of 733 bp encodes a protein
      (M(r) 24.1 kDa) consisting of 214 amino acids. Comparison of the predicted amino
      acid sequence revealed relatively high homology to that of DdEF-1 beta from
      silkworm (59%), human (57%) and Xenopus (55%). Northern analysis showed that the
      DdEF-1 beta mRNA is maximally expressed during the vegetative growth phase,
      followed by marked decrease in response to cell differentiation induced by
      starvation.

PMID- 9546042
TI  - Isolation of a new member of DnaJ-like heat shock protein 40 (Hsp40) from human
      liver.
AB  - A new member of Hsp40, HLJ1, consisting of 337 amino acids, was cloned from a
      human liver cDNA library. The deduced amino acid sequence of HLJ1 has an 84%
      homology (69% identity) with that of HDJ-1 isolated from human placenta. Northern
      analysis showed that expression of the HLJ1 gene is heat-inducible and its
      transcription shows some degree of preference in heart, skeletal muscle, and
      pancreas.

PMID- 9546044
TI  - Melatonin and serotonin interactions with calmodulin: NMR, spectroscopic and
      biochemical studies.
AB  - It has been reported that the hormone melatonin binds tightly to the ubiquitous
      calcium-regulatory protein, calmodulin (CaM) with a Kd value around 0.1 nM
      [Benitez-King et al., Biochim. Biophys. Acta, 1290 (1993) 191-196]. Normally CaM
      only binds to target proteins and various 20-residue synthetic peptides
      encompassing the CaM-binding domain of these target proteins with K(d) values
      ranging between 1.0 microM and 0.1 nM. Here we have studied the interaction of
      melatonin and several structurally related compounds--serotonin, 5
      hydroxytryptophan, and tryptophan--to CaM through gel band shift assays,
      enzymatic competition assays with calcineurin, fluorescence spectroscopy, far and
      near UV circular dichroism spectropolarimetry and NMR spectroscopy. Fluorescence
      spectra show that the binding is calcium dependent. NMR studies with
      biosynthetically labelled methyl-13C-Met CaM show that melatonin and the other
      compounds interact with the hydrophobic cleft regions of the protein. Our NMR
      data show that melatonin binds to both domains of the dumbbell-shaped CaM, while
      serotonin appears to bind only to the C-terminal domain. This binding mode is
      further substantiated by fluorescence and gel band shift competition experiments
      with synthetic peptides from myosin light chain kinase and constitutive nitric
      oxide synthase. Circular dichroism spectra indicate that the secondary structure
      of CaM is not altered by addition of melatonin. Our data are internally
      consistent and reveal Kd values in the mM range for melatonin. Thus the binding
      of these compounds to CaM is substantially weaker than was previously reported
      and is unlikely to be of physiological significance.

PMID- 9546043
TI  - Legume lectin structure.
AB  - The legume lectins are a large family of homologous carbohydrate binding proteins
      that are found mainly in the seeds of most legume plants. Despite their strong
      similarity on the level of their amino acid sequences and tertiary structures,
      their carbohydrate specificities and quaternary structures vary widely. In this
      review we will focus on the structural features of legume lectins and their
      complexes with carbohydrates. These will be discussed in the light of recent
      mutagenesis results when appropriate. Monosaccharide specificity seems to be
      achieved by the use of a conserved core of residues that hydrogen bond to the
      sugar, and a variable loop that determines the exact shape of the monosaccharide
      binding site. The higher affinity for particular oligosaccharides and
      monosaccharides containing a hydrophobic aglycon results mainly from a few
      distinct subsites next to the monosaccharide binding site. These subsites consist
      of a small number of variable residues and are found in both the mannose and
      galactose specificity groups. The quaternary structures of these proteins form
      the basis of a higher level of specificity, where the spacing between individual
      epitopes of multivalent carbohydrates becomes important. This results in
      homogeneous cross-linked lattices even in mixed precipitation systems, and is of
      relevance for their effects on the biological activities of cells such as
      mitogenic responses. Quaternary structure is also thought to play an important
      role in the high affinity interaction between some legume lectins and adenine and
      a series of adenine-derived plant hormones. The molecular basis of the variation
      in quaternary structure in this group of proteins is poorly understood.

PMID- 9546045
TI  - Substrate specificity of cellobiose dehydrogenase from Phanerochaete
      chrysosporium.
AB  - Substrate structural mapping suggests that the catalytic site of cellobiose
      dehydrogenase from Phanerochaete chrysosporium forms a narrow cave with two
      hexose binding subsites. Kinetic data also show that beta-di or oligosaccharides
      are favored electron donors with respect to both KM and kcat. Surprisingly,
      thiocellobiose showed an even higher kcat than cellobiose, although the KM value
      was somewhat higher. The CDH was purified using an updated protocol.

PMID- 9546046
TI  - Primary structures of Arenicola marina isomyoglobins: molecular basis for
      functional heterogeneity.
AB  - The primary structures of isomyoglobins MbI and MbII from the body wall
      musculature of the polychaete Arenicola marina were investigated, aiming to trace
      the molecular basis for their functional differentiation. Unexpectedly, five
      chains, MbIa, MbIb, MbIIa, MbIIb and MbIIc, each consisting of 145 amino-acid
      residues and occurring in a ratio of = 33:17:25:12.5:12.5 were found. All
      substitutions can be explained by one-point mutations. With the exception of the
      41(C6)Asn-->Asp(MbI/MbII) exchange that appears to be the basis for the
      electrophoretic separation of MbI and MbII, the substitutions do not involve
      drastic changes in the character of the side-chains. Pairwise comparison of MbIa
      and MbIIa with other invertebrate globin chains indicate the following sequence
      of decreasing identities: Aplysia (mollusc) Mb, Chironomus (insect) CTT III
      hemoglobin, whale Mb and Ascaris (nematode) Mb. The marked difference in O2
      affinities between MbI and MbII appears attributable to 62Pro which distorts the
      E helix around E6 and occurs in all MbII chains, but in only 33% of the MbI
      chains (MbIb).

PMID- 9546047
TI  - Catalytic properties of the cysteine aminopeptidase PepC, a bacterial bleomycin
      hydrolase.
AB  - PepC is a cytoplasmic thiol aminopeptidase widely conserved among lactic acid
      bacteria. PepC from Lactococcus lactis shares 35-38% identity with
      aminopeptidases of eukaryotic origins: the yeast and mammalian bleomycin
      hydrolases (BLMase). In this work we investigated the hydrolytic activity of PepC
      towards various substrates: bleomycin A2, aminoacyl-p-nitroanilides (pNA) and
      peptides. First, we found the bleomycin hydrolase activity of lactococcal PepC
      and measured similar kinetics parameters to those reported for the mammalian
      BLMase. Second, the results obtained on aminoacyl-pNA confirmed the capacity of
      the enzyme to release a broad range of amino acids and the pH activity profile
      suggests the presence of an ionic interaction between the enzyme and the free
      alpha-amino group of the substrate. Third, the aminopeptidase activity measured
      on peptide substrates revealed that PepC possesses an extended binding site which
      interacts with the peptidic backbone of the substrate. The hydrolytic efficiency
      is highly dependent on the length of the peptide, optimal for tetrapeptides and
      further enhanced by the presence of hydrophobic residues in the P' positions of
      the substrate. These enzymatic properties are of importance for the design of
      specific inhibitors and the biological function of the bleomycin hydrolases.

PMID- 9546048
TI  - Dual effect of actin on the accessibility of myosin essential light chain A1 to
      papain cleavage.
AB  - The influence of various amounts of actin on the proteolytic susceptibility of
      myosin essential light chain (ELC) A1, the binding of isolated A1 light chain and
      the N-peptide spanning N-terminal sequence of A1 to actin is studied to obtain
      more information on the role of the N-terminus of A1 light chain in the myosin
      actin interaction. Low ratios of actin to myosin (1:1) lead to stimulate
      cleavage, whereas higher ratios (4:1) lead to protection of A1. Exposure of A1 by
      actin is especially seen in heavy meromyosin (HMM) and monomeric myosin and this
      is probably related to the full saturation of actin protomers with myosin heads.
      The protecting action of actin on A1 cleavage is more pronounced in myosin
      filaments. Conditions favoring the saturation of myosin regulatory light chain
      (RLC) with calcium ions instead of magnesium ions promotes the protection of A1.
      Cross-linking of HMM and actin results in higher yields of A1-actin product at
      high actin to myosin heads ratios. Isolated A1 light chain is pelleted by actin.
      A synthetic peptide spanning the N-terminal sequence of A1 can be cross-linked to
      actin. It is postulated that the protective action of actin on A1 papain cleavage
      is caused by the binding of the A1 N-terminus to actin. Changes in the RLC
      phosphorylation level and magnesium-for-calcium exchange in RLC may affect the
      probability of this interaction.

PMID- 9546049
TI  - Interaction of quinones with Arabidopsis thaliana thioredoxin reductase.
AB  - In view of the ubiquitous role of the thioredoxin/thioredoxin reductase (TRX/TR)
      system in living cells, the interaction of Arabidopsis thaliana NADPH-thioredoxin
      reductase (EC 1.6.4.5) with quinones, an important class of redox cycling and
      alkylating xenobiotics, was studied. The steady-state reactions of A. thaliana TR
      with thioredoxin (TRX) and reaction product NADP+ inhibition patterns were in
      agreement with a proposed model of E. coli enzyme (B.W. Lennon, C.H. Williams,
      Jr., Biochemistry, vol. 35 (1996), pp. 4704-4712), that involved enzyme cycling
      between four- and two-electron reduced forms with FAD being reduced. Quinone
      reduction by TR proceeded via a mixed single- and two-electron transfer, the
      percentage of single-electron flux being equal to 12-16%. Bimolecular rate
      constants of quinone reduction (kcat/km) and reaction catalytic constants (kcat)
      increased upon an increase in quinone single-electron reduction potential. E(1)7.
      In several cases, the kcat of quinone reduction exceeded kcat of TRX reduction,
      suggesting that quinones intercepted electron flux from TR to TRX. Incubation of
      reduced TR with alkylating quinones resulted in a rapid loss of TRX-reductase
      activity, while quinone reduction rate was unchanged. In TRX-reductase and
      quinone reductase reactions of TR, NADP+ exhibited different inhibition patterns.
      These data point out that FAD and not the catalytic disulfide of TR is
      responsible for quinone reduction, and that quinones may oxidize FADH2 before it
      reduces catalytic disulfide. Most probably, quinones may oxidize the two-electron
      reduced form of TR, and the enzyme may cycle between two-electron reduced and
      oxidized forms in this reaction. The relatively high rate of quinone reduction by
      A. thaliana thioredoxin reductase accompanied by their redox cycling, confers pro
      oxidant properties to this antioxidant enzyme. These factors make plant TR an
      attractive target for redox active and alkylating pesticide action.

PMID- 9546050
TI  - X-ray crystal structure of papain complexed with cathepsin B-specific covalent
      type inhibitor: substrate specificity and inhibitory activity.
AB  - The Ile-Pro sequence of CA074, potent covalent-type inhibitor, is necessary to
      exhibit the specificity for cathepsin B, but not for papain. In order to
      elucidate how its sequence binds to papain and why such binding does not exhibit
      the specificity for papain at the atomic level, two CA074-related compounds, 1 (N
      (L-3-carboxyloxirane-2-carbonyl)-L-isoleucyl-L-proline) and 2 (N-(L-3
      carboxyloxirane-2-carbonyl)-L-isoleucyl-diethylamide), were designed and their
      structure--inhibitory activity relationship was investigated by the X-ray crystal
      analyses of the complexes with papain. The Ile-Pro moiety of 1 was located at the
      S2 and S3 subsites consisting of Val-133, Val-157, and Asp-158 and of Tyr-61, Gly
      66, and Tyr-67 residues of papain, respectively, which is in contrast with the
      binding of CA074 to S'n (n = 1 approximately 2) subsites in the complex with
      cathepsin B. Although 2 in the complex with papain showed the similar binding
      pattern to 1, its inhibitory activity was about two-fold higher than of 1,
      suggesting the importance of tight S3-P3 hydrophobic interaction for the
      activity. The difference of the substrate specificity between papain and
      cathepsin B has also been discussed based on the X-ray results of the present and
      cathepsin B-inhibitor complexes.

PMID- 9546051
TI  - The purification and characterization of a Trichoderma harzianum exochitinase.
AB  - A chitinolytic enzyme was purified from the culture filtrate of T. harzianum
      (T198) by precipitation with ammonium sulphate followed by affinity binding to
      swollen chitin and release with 10% (v/v) acetic acid. The molecular weight of
      the enzyme was calculated to be 28 and 27.5 kD by gel filtration chromatography
      and SDS-PAGE, respectively. The isoelectric point of the enzyme was 7.4. The pH
      optimum for activity was 3.5 and maximum activity was obtained at 50 degrees C.
      The enzyme displayed activity on a wide array of chitin substrates of more than
      two N-acetylglucosamine units in length. HPLC analysis of hydrolysis products
      demonstrated that the enzyme was an exochitinase releasing N-acetylglucosamine
      only.

PMID- 9546052
TI  - Probing the ATP binding site of tubulin with thiotriphosphate analogues of ATP.
AB  - Tubulin assembly studies with GTP alpha S diastereoisomers have shown that there
      is stereoselectivity at the alpha-phosphate binding region of tubulin. GTP alpha
      S(Sp) bound tighter than GTP alpha S(Rp) and promoted nucleation and assembly
      better than GTP and GTP alpha S(Rp). ATP and dATP have been reported to bind
      weakly to tubulin and to be less effective than GTP and dGTP in promoting tubulin
      assembly. This study was done to learn if ATP alpha S(Sp) and dATP alpha S(Sp)
      are good promoters of tubulin assembly and to compare these ATP thiotriphosphate
      analogues to the corresponding GTP analogues in tubulin assembly. Studies were
      also done with ATP alpha S(Rp), GTP, ATP beta S(Sp) and ATP gamma S. At least
      three cycles of tubulin (25 microM) assembly-disassembly were found with 1 mM ATP
      alpha S(Sp) and dATP alpha S(Sp) and both nucleotides were incorporated and
      hydrolyzed in the polymers. Less dATP alpha S(Sp) (25 microM) than ATP alpha
      S(Sp) (100 microM) promoted assembly to 50% of the maximum value. The critical
      concentrations (Cc) for assembly with 1 mM nucleotide were low for ATP alpha
      S(Sp) (3 microM) and dATP alpha S(Sp) (2 microM) and compared favorably with GTP
      (5 microM), GTP alpha S(Sp) (2 microM) and dGTP alpha S(Sp) (1 microM). Both 1 mM
      ATP and dATP were poor promoters of tubulin assembly and were not detected in the
      polymers. The predominant structures induced by 1 mM (ATP alpha S(Sp) and dATP
      alpha S(Sp) were bundles of sheets and microtubules, which were more stable to
      the cold and to Ca(II) than microtubules assembled with GTP, ATP or dATP. ATP
      alpha S(Rp) (1 mM) did not promote assembly suggesting that there is
      stereoselectivity at the ATP alpha S alpha-phosphate binding region of tubulin as
      there is with GTP alpha S diastereoisomers. ATP alpha S(Sp) and dATP alpha S(Sp)
      mimic GTP alpha S(Sp) and dGTP alpha S(Sp) in tubulin assembly since all four
      nucleotides promote bundles of tubulin in buffer with glycerol, and the deoxy
      nucleotides have lower Cc, shorter lags and faster rates for tubulin assembly.

PMID- 9546053
TI  - Interaction of M1 and M2 isozymes pyruvate kinase from human tissues with
      phospholipids.
AB  - The effect of pH and the presence of FBP on the interaction of skeletal muscle
      (PK-M1) and kidney or tumor meningioma (PK-M2) pyruvate kinase with the
      phospholipids liposomes were investigated by ultracentrifugation and steady-state
      kinetics and were compared with those results obtained using the bovine heart (PK
      M1) isoenzyme which we previously studied. Pyruvate kinase specific activity
      increases upon the interaction with liposomes. The activation is specifically
      sensitive to presence of phosphatidylserine (PS) in liposomes. Liposomes made of
      phosphatidylcholine + phosphatidylserine mixture are good adsorptive systems for
      both human and bovine of M-type isozymes at low ionic strength. Interaction of PK
      M1 with PS liposomes results in the change of Vmax and K(m) values for PEP
      without marked effect on Hill coefficients. Addition of PS liposomes to PK-M2
      induces hyperbolic saturation curves for PEP.

PMID- 9546054
TI  - A molecular model for the d chain of the giant haemoglobin from Lumbricus
      terrestris and its implications for subunit assembly.
AB  - A structural model for the monomeric d chain of the giant haemoglobin from
      Lumbricus terrestris is described. Based on the crystal structures of other
      globins, the model provides evidence for the existence of a novel tryptophan-haem
      interaction. The observation that all three tryptophans are buried within the
      hydrophobic core is consistent with fluorescence data on the isolated monomer and
      the intact molecule. The model has also been used to predict the probable
      arrangement of the abcd tetramer as being similar to that observed in the clam Hb
      II structure. Such predictions allow the identification of four residues of
      particular importance in stabilising one of the subunit-subunit interfaces:
      Arg48, Arg97, His89 and Gln93. The latter two may be of special importance in the
      mediation of cooperative effects within the tetramer and indeed the intact
      molecule.

PMID- 9546055
TI  - An electrospray ionization mass spectrometric study of the extracellular
      hemoglobins from Chironomus thummi thummi.
AB  - The aquatic larvae of the dipteran, Chironomus thummi thummi contain
      extracellular hemoglobins which exhibit stage-specific expression. We have used
      maximum entropy-based deconvolution of the complex, multiply charged electrospray
      ionization mass spectra, to demonstrate the presence of more than 20 components,
      ranging in mass from 14,417.3 Da to 17,356.5 Da in the 4th instar larvae. Of the
      15 major peaks with intensities > 10 relative to 100 for the 14,417.3 Da
      component (CTT-IV), only the 15,528.2-Da peak does not correspond to a known
      amino acid sequence. Since the number of C. thummi thummi globin genes now stands
      at 27, including one cDNA and not counting three that must encode known globins,
      our results suggest that only a limited number of the globin genes are expressed
      in the 4th instar larvae.

PMID- 9546056
TI  - Long-lifetime Ru(II) complexes for the measurement of high molecular weight
      protein hydrodynamics.
AB  - We describe the synthesis and characterization of two asymmetrical ruthenium(II)
      complexes, [Ru(dpp)2(dcbpy)]2+ and [Ru(dpp)2(mcbpy)]2+, as well as the water
      soluble sulfonated derivatives [Ru(dpp(SO3Na)2)2(dcbpy)]2+ and
      [Ru(dpp(SO3Na)2)2(mcbpy)]2+ (dpp is 4,7-diphenyl-1,10-phenanthroline, dcbpy is
      4,4'-dicarboxylic acid-2,2'-bipyridine, mcbpy is 4-methyl,4'-carboxylic acid-2,2'
      bipyridine, and dpp(SO3Na)2 is the disulfonated derivative of dpp) as probes for
      the measurement of the rotational motions of proteins. The spectral (absorption,
      emission, and anisotropy) and photophysical (time-resolved intensity and
      anisotropy decays) properties of these metal-ligand complexes were determined in
      solution, in both the presence and absence of human serum albumin (HSA). These
      complexes display lifetimes ranging from 345 ns to 3.8 microseconds in
      deoxygenated aqueous solutions under a variety of conditions. The carboxylic acid
      groups on these complexes were activated to form N-hydroxysuccinimide (NHS)
      esters which were used to covalently lable HSA, and were characterized
      spectroscopically in the same manner as above. Time-resolved anisotropy
      measurements were performed to demonstrate the utility of these complexes in
      measuring long rotational correlation times of bioconjugates between HSA and
      antibody to HSA. The potential usefulness of these probes in fluorescence
      polarization immunoassays was demonstrated by an association assay of the Ru(II)
      labeled HSA with polyclonal antibody.

PMID- 9546057
TI  - Redox potential of the haem c group in the quinocytochrome, lupanine hydroxylase,
      an enzyme located in the periplasm of a Pseudomonas sp.
AB  - The quinocytochrome c, lupanine hydroxylase, was shown to be located in the
      periplasm of a Pseudomonas sp. The midpoint redox potential of the haem in the
      purified enzyme was measured by potentiometric titration and shown to be +193 mV.
      PQQ was removed from the enzyme by isoelectric focusing to give inactive
      apoenzyme. This resulted in a shift in the midpoint redox potential of the haem
      to +98 mV. Full activity was recovered by the addition of PQQ to apoenzyme that
      also restored the original potential.

PMID- 9546058
TI  - Effect of pressure on the catalytic activity of subtilisin Carlsberg suspended in
      compressed gases.
AB  - We studied the effect of pressure up to 300 bar on the catalytic efficiency of
      subtilisin Carlsberg suspended in compressed propane, near-critical ethane, near
      critical carbon dioxide and tert-amyl alcohol, at constant temperature and fixed
      enzyme hydration. Increasing pressure lowered the catalytic efficiency of the
      enzyme in all the solvents, resulting in positive activation volumes, delta V#.
      The delta V# values in compressed propane and in tert-amyl alcohol were similar
      and larger in magnitude than the value reported in the literature for the same
      reaction in an aqueous buffer, although within the range of typical delta V#
      values in aqueous media. In the near-critical fluids, the delta V# were much
      larger, e.g., an increase in pressure of only 200 bar causing a sixfold decrease
      in the catalytic efficiency of subtilisin in carbon dioxide. These data should
      reflect the proximity of ethane and carbon dioxide to the critical point, and the
      resulting condensation of solvent molecules about the solutes, yielding negative
      solute partial molar volumes.

PMID- 9546059
TI  - Pediatric brain tumors: loss of heterozygosity at 17p and TP53 gene mutations.
AB  - Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of
      the central nervous system (CNS) have demonstrated material losses of 17p, the
      region that contains the TP53 gene, as the most frequent abnormality. Mutations
      in the TP53 gene are, however, very rare in these tumors. These findings strongly
      suggest that another, as yet unidentified, gene on 17p may be involved. We
      performed a search for loss of heterozygosity (LOH) on 17p by microsatellite
      markers on 26 childhood CNS tumors as well as TP53 gene mutations (exons 5-8) by
      single-strand conformational polymorphism analysis on 41 pediatric brain tumor
      samples of distinct histologic types. LOH was detected in 10 cases: 7 PNET, 2
      astrocytomas, and 1 glioblastoma multiforme. In 4 of the PNETs the losses were
      limited to more distal markers. On the other hand, TP53 mutations were detected
      in 6 of 41 samples studied. Our results not only confirm the low penetrance of
      the TP53 gene on pediatric CNS tumors, but also provide further evidence of a
      putative tumor suppressor gene distal to TP53, between markers (D17S938, D17S926)
      and 17pter, specifically taking part in the development of PNET.

PMID- 9546060
TI  - Characterization of a malignant eccrine poroma by cytogenetic and fluorescence in
      situ hybridization techniques.
AB  - We have cytogenetically and by fluorescence in situ hybridization (FISH) analyzed
      short-term cultures from a malignant eccrine poroma, a type of tumor in which
      chromosomal abnormalities have previously not been reported. Combining the
      results from G-banding and FISH, the karyotype was interpreted as
      50,XX,t(3;11;12)(q21;p15;q15),+5,+7,+9,
      +9,t(12;22)(q13;q13),+del(12)(q15),der(15)t(3;15)
      (q23;p13),der(17)t(8;17)(q22;p13),-20,add(22)(q13).

PMID- 9546061
TI  - Normal and rearranged PAX3 expression in human rhabdomyosarcoma.
AB  - PAX3, a member of the PAX-gene family, encodes a nuclear transcription factor
      that is transiently expressed in the neural tube and in muscle progenitor cells
      and regulates embryonal development in the mouse. Together with the FKHR gene it
      is involved in the t(2;13)(q35;q14), a specific translocation associated with
      alveolar rhabdomyosarcoma (ARMS). As a consequence of the rearrangement two
      chimeric transcripts originate: FKHR-PAX3 and PAX3-FKHR. We studied the
      expression of wild type PAX3 and the chimeric transcripts originating from the
      t(2;13) in a series of 23 rhabdomyosarcomas (RMS) of childhood, by reverse
      transcriptase polymerase chain reaction (RT-PCR). Wild type PAX3 was detected in
      48% of the RMS, whereas another 39% were positive only after nested PCR. Normal
      adult-skeletal muscle showed a very weak expression of PAX3, but fetal muscle did
      not express PAX3. PAX3-FKHR was found in 11 of 15 alveolar RMS, 7 of which were
      positive also for the reciprocal transcript, whereas no RMS expressed FKHR-PAX3
      alone. These results confirm that the PAX3-FKHR transcript is specifically
      associated with the alveolar RMS and that it is a more sensitive marker of the
      t(2;13) than the reciprocal product FKHR-PAX3. Furthermore, the finding of PAX3
      expression with or without PAX3-FKHR transcript in the great majority of the
      cases raises the question of whether PAX3 expression could play a role in the
      pathogenesis of RMS.

PMID- 9546062
TI  - Mutation of the 5' noncoding region of the BCL-6 gene in low-grade gastric
      lymphoma of the mucosa-associated lymphoid tissue.
AB  - BCL-6 gene rearrangement and hypermutations were investigated in four Hong Kong
      Chinese patients with low-grade gastric lymphoma of the mucosa-associated
      lymphoid tissue (MALToma). The former was studied by Southern analysis and the
      latter by the technique of polymerase chain reaction and denaturing gradient gel
      electrophoresis. BCL-6 gene rearrangement was not detectable in any of the four
      cases. However, mutations at both the E1.11 and E1.12 segments of the 5'
      noncoding region of the BCL-6 gene were found in two patients. This preliminary
      observation suggests that the mutations of the 5' noncoding region of the BCL-6
      gene rather than gene rearrangement may be playing a more important role in the
      tumorigenesis of low-grade gastric MALToma. Further confirmation of this finding
      by studying a larger number of patients will be required.

PMID- 9546063
TI  - Fluorescence in situ hybridization to assess aneuploidy for chromosomes 7 and 8
      in hematologic disorders.
AB  - Stored, fixed cell suspensions of bone marrows from 70 patients karyotyped over a
      three-year period for myelodysplastic syndrome (MDS) or related hematologic
      conditions were retrospectively studied in two series using centromeric probes
      for chromosomes 7 and 8. Series I consisted of patient samples with numerical
      and/or structural abnormalities of chromosomes 7 or 8, matched with chromosomally
      normal samples from about the same time period. Series II consisted of
      consecutive MDS patient samples as well as patient samples in which one or more
      cells had numerical or structural abnormalities of 7 and 8. In both series,
      probes for chromosomes 7 and 8 were applied in each case and at least 100 nuclei
      were scored for each probe for the distribution of one, two, or three signals.
      Twenty-seven cases had clonal abnormalities by routine cytogenetics (RC): 12 with
      monosomy 7; one with monosomy 8; five with trisomy 8; nine with clonal
      abnormalities other than 7 or 8 aneuploidy. Eleven cytogenetically normal cases
      gave abnormal interphase FISH (IF) results; one was subsequently confirmed by
      metaphase FISH analysis to have a clonal structural abnormality of chromosome 7;
      one case with a trisomy 8 clone, in remission by RC, showed 35% of cells by IF
      with three signals for chromosome 8; one case had heteromorphic chromosomes by
      FISH. Of eight remaining cases, five (four with -7 and one with +8 by IF) were
      among 22 cases of cytogenetically normal MDS. Three remaining cases (two with +8
      and one with both +7 and +8 by IF) had AML or MPD. The high rate of possible
      undetected monosomy 7, among MDS cases in particular, suggests all MDS cases
      should be screened by IF.

PMID- 9546065
TI  - Two new cases of near-tetraploidy in adult acute myeloid leukemia.
AB  - Tetraploid or near-tetraploid karyotype has been described rarely in hematologic
      neoplasms. Herein we report two new cases of adult acute myeloblastic leukemia,
      M0 and M1 FAB subtypes that showed near-tetraploid clones that were studied with
      conventional cytogenetics and in situ hybridization (ISH). We compare our new
      cases with those previously reported.

PMID- 9546064
TI  - Chromosomal abnormalities in two bladder carcinomas with secondary squamous cell
      differentiation.
AB  - Two secondary squamous cell carcinomas of the bladder (i.e., tumors that
      originated from primary transitional cell carcinomas) were examined
      cytogenetically. Both tumors showed complex karyotypes with many of the same
      aberrations that have formerly been described in transitional cell carcinomas.
      Monosomy 9, trisomy 7, and rearrangements of chromosomes 3, 8, 10, 13, and 17
      were common to both tumors. Among other changes that have been implicated in
      bladder carcinogenesis, an isochromosome for 5p was seen in one tumor and loss of
      11p material in the other. Our findings indicate that secondary squamous cell
      carcinomas of the bladder are karyotypically indistinguishable from advanced
      transitional cell carcinomas of the same organ. The putative genetic changes that
      steer the differentiation of the neoplastic epithelium in the direction of
      squamous cells thus remain unknown.

PMID- 9546066
TI  - Gastrointestinal stromal tumor, uncommitted type, with monosomies 14 and 22 as
      the only chromosomal abnormalities.
AB  - Karyotypic analysis of a gastric stromal tumor with the histologic and
      immunohistochemical features of a malignant, uncommitted lesion revealed clonal
      monosomies of chromosomes 14 and 22. Such changes, together with loss of
      chromosomes 15 and 18, as well as structural rearrangements involved chromosome
      1, have been previously reported in gastrointestinal stromal tumors with smooth
      muscle differentiation. We suggest that monosomies of chromosomes 14 and 22 are
      early events in the malignant transformation of the mesenchymal cell-originating
      gastrointestinal stromal tumors.

PMID- 9546067
TI  - Cytogenetic chromosomal preparations using 2-methoxyestradiol.
AB  - The antimitotic drug 2-methoxyestradiol is an end metabolite of catechol
      estrogens. In vivo, it arrests cells in mitosis by interfering with the dynamics
      of the mitotic spindle without disrupting tubulin formation. It has a mitotic
      index similar to that of Colcemid in different cell lines. Here we report that 2
      methoxyestradiol can be used for making cytogenetic preparations of comparable
      quality to that of colcemid. In addition, 2-methoxyestradiol is devoid of the
      toxicity associated with Colcemid, which may make 2-methoxyestradiol useful in
      slowly growing samples often found in primary solid tumor cultures where a
      sufficient number of mitotic cells is difficult to obtain.

PMID- 9546068
TI  - Cytogenetic findings in an embryonal sarcoma of the liver.
AB  - An undifferentiated embryonal sarcoma (malignant mesenchymoma) of the liver from
      a 5-year-old girl was found to have near-triploid and near-hexaploid clones with
      several chromosomal rearrangements. This is the first description of the
      chromosomal changes in this tumor type.

PMID- 9546069
TI  - Splenic lymphoma with villous lymphocytes showing del(7) and inv(10).
AB  - A 49-year-old woman presented with splenic lymphoma with villous lymphocytes
      (SLVL) that showed a clonal abnormality of del(7)(q22q32) in addition to
      inv(10)(p13q23), the latter being a previously undescribed abnormality in chronic
      lymphoproliferative disorders. A review of the literature on cytogenetic
      abnormalities of SLVL indicates that del(7q) is strongly associated with SLVL and
      may be important in the pathogenesis of this disorder.

PMID- 9546070
TI  - Fluorescence in situ hybridization reveals trisomy 2q by insertion into 9p in
      hepatoblastoma.
AB  - Cytogenetics and fluorescence in situ hybridization (FISH) of a hepatoblastoma
      are presented. The results of standard chromosome analysis were as follows:
      47,XY,+2,add(4)(q35),-9,+20[10]. FISH with the use of whole-chromosome paints
      revealed partial trisomy of the long arm of chromosome 2 by insertion into
      chromosome 9. Comparison of the G-banded metaphases with metaphase FISH led to a
      reinterpretation of the karyotype as:
      47,XY,add(4)(q35),der(9)ins(9;2)(p22;q?21q?25),+20. This case supports previous
      observations that the critical region of trisomy 2 lies between 2q21 and 2qter
      and shows how partial trisomy 2q may evade detection in G-banded metaphases.

PMID- 9546071
TI  - Rare constitutional Robertsonian translocation in a childhood acute lymphoblastic
      leukemic patient.

PMID- 9546072
TI  - True extended haplotypes of p53: indicators of breast cancer risk.

PMID- 9546073
TI  - Cytogenetic analysis of cells from endometriotic cysts of the human ovary.

PMID- 9546074
TI  - Correction of the Bloom syndrome cellular phenotypes.
AB  - Bloom syndrome (BLM) is a genetic disorder associated with predisposition to
      cancer and chromosome instability. However, the most readily recognized clinical
      feature of the syndrome is growth retardation. Introduction of the previously
      cloned BLM gene into BLM cells yielded correction of the chromosome instability
      and slow growth phenotypes. Additionally, asynchronous cultures of complemented
      clones revealed a lower percentage of cells in S-phase than uncomplemented BLM
      cells. These results support the notion that BLM is a defect in which short
      stature, chromosome instability and cancer predisposition are all associated with
      an error in DNA replication.

PMID- 9546075
TI  - Cell cycle control is aberrant in Chinese hamster ovary cell mutants exhibiting
      apoptosis after serum deprivation.
AB  - We isolated mutants of Chinese hamster ovary cells that exhibit excessive
      apoptosis after serum deprivation. In the medium containing 10% serum, the growth
      rates of the mutants were 1.4 to 1.5-fold faster than those of wild-type cells.
      Whereas the cell cycle of wild-type cells was arrested at the G1 phase after
      serum deprivation, the cell cycle of the mutant cells was not fully arrested at
      this phase, suggesting that cell cycle regulation was disorganized in the
      mutants. The mutants were highly sensitive to a nucleotide-analogue 5
      fluorouracil in the absence of serum, whereas wild-type cells were resistant to
      the drug. Based on the sensitivity to the drug after serum deprivation, we could
      classify the mutants into dominant groups and at least two recessive
      complementation groups. Thus, these mutants presumably contain different lesions
      in gene(s) required for cell cycle regulation and apoptosis.

PMID- 9546076
TI  - Applications of green fluorescent protein as a marker of retroviral vectors.
AB  - The Green Fluorescent Protein (GFP) of Aequorea victoria is used as a vital
      fluorescent tag for the detection and isolation of genetically modified cells.
      Several modified variants of GFP were tested as marker genes in retroviral
      vectors containing different backbones and promoter combinations. Constructs
      allowing for reliable detection of GFP fluorescence and the expression of a
      cotransduced gene from a strong promoter were identified. Cells harboring such
      constructs are detectable by flow cytometry, fluorescence microscopy and multi
      well fluorescence reading. GFP expression in transduced cells is stable both in
      vitro and in vivo, and long-term dynamics of GFP-positive fractions in a mixed
      population can be used to monitor the biological effects of a cotransduced gene.
      Selection of cells with the highest GFP fluorescence enriches for multiply
      infected cells. The use of different GFP variants allows one to monitor
      simultaneously two cell populations transduced with vectors carrying GFPs that
      differ in their fluorescence intensity or spectral properties and to identify
      doubly transduced cells. In addition, transcription of an inducible promoter
      positioned in the opposite orientation to GFP can be monitored by the inhibition
      of GFP fluorescence. Thus, GFP provides a useful marker for gene transfer by
      retroviral vectors and extends the range of applications for retroviral
      transduction.

PMID- 9546078
TI  - Assignment of three human markers in chromosome 21q11 to mouse chromosome 16.
AB  - Three unique sequence microclones from human chromosome region 21q11 were
      assigned to mouse chromosome 16 using a mouse/Chinese hamster cell hybrid 96Az2
      containing a single mouse chromosome 16. This comparative mapping provides
      further homology between human chromosome 21 and mouse chromosome 16 to include
      the very proximal portion of the long arm of human chromosome 21. Since this part
      of human chromosome 21 is associated with mental retardation in Down syndrome
      individuals, its homologous mouse region should also be included in the
      construction of mouse models for studying Down syndrome phenotypes including
      mental retardation.

PMID- 9546077
TI  - Phenotypic correction of ataxia-telangiectasia cellular defect by exogenously
      introduced human or mouse subchromosomal fragments.
AB  - A human-mouse hybrid containing a human 11q22-23 fragment including the ATM locus
      was used to examine its capability to correct the cellular defect of ataxia
      telangiectasia (A-T). Examination of 21 A-T-derived hybrids indicated that the
      acquired radioresistance was observed in the clones where the 11q22-23 fragment
      was transferred intact, but not in those where donor-derived 11q segment was
      lost. In one exceptional clone, the ATM locus was deleted from the transferred
      fragment, while it was still partially radioresistant. This partially
      radioresistant clone was found to include the mouse-derived fragment containing
      the Atm gene, the mouse homologue of human ATM gene. Similar association of
      partial radioresistance with the presence of mouse Atm gene was observed in three
      additional hybrids. The results indicate that the cellular A-T defect can be
      corrected by the mouse subchromosomal fragment containing the Atm gene as well as
      by the human 11q22-23 fragment containing the ATM gene, but apparently to a
      lesser extent in the former.

PMID- 9546079
TI  - [The knowledge of pediatricians in Salvador, Brazil about measles vaccine].
AB  - The success of international initiatives for the eradication of measles depends
      in large part on knowledge about vaccination. In 1992, a cross-sectional study
      was carried out to evaluate knowledge about measles vaccine among pediatricians
      in the Brazilian city of Salvador, Bahia. Of the 506 pediatricians residing in
      the city, 299 (59%) could be located and responded to a questionnaire containing
      15 questions that posed hypothetical situations regarding indications and
      contraindications for this vaccine. The average number of correct responses was
      9.3 out of 15, which illustrates the pediatricians' poor knowledge of measles
      vaccine. Conditions commonly seen in pediatric practice in Brazil--malnutrition,
      upper respiratory tract infection, diarrhea, and prematurity--were often
      erroneously considered contraindications for immunization. More than half (62%)
      of the pediatricians did not know the correct way to administer the vaccine.
      Knowledge about the vaccine did not differ according to the length of time that
      had elapsed since the physicians' university training in pediatrics or as a
      result of working in health centers operated by the State Health Secretariat.
      University professors, pediatricians with a postgraduate degree, and those
      pursuing postgraduate studies scored slightly higher than the rest. These results
      point to the need to strengthen training on measles vaccination in medical
      schools and programs of continuing education for pediatricians.

PMID- 9546080
TI  - [The prevalence of non-insulin-dependent diabetes mellitus in the rural
      population of Durango, Mexico].
AB  - This study was carried out to determine the prevalence of non-insulin-dependent
      diabetes mellitus (NIDDM) in rural inhabitants of Durango, Mexico, and some of
      the risk factors for the disease. A random samples of 30,996 individuals aged 30
      years and over was selected from 627 rural communities in Durango. These persons
      were interviewed between November 1993 and December 1994 to obtain information on
      several sociodemographic variables. A capillary blood sample was collected from
      each individual to determine his or her glucose level after 10-12 hours of
      fasting. Measures of central tendency and dispersion were calculated, and
      percentage distributions for the study variables were determined. Comparisons
      among proportions were made utilizing the chi-square test, and means were
      compared using Student's t test. The strength of associations was estimated with
      odds ratios, and 95% confidence intervals (CI 95%) were calculated for
      proportions. The final sample consisted of 31,028 persons, of whom 22,890 (73.8%)
      were women and 8,138 (26.2%) were men. A total of 1,004 cases of NIDDM were
      detected (3.2%; CI 95%:3.0 to 3.4), 767 in women and 237 in men. Only 9.2% of the
      study population was obese. The highest frequency of NIDDM was documented in
      persons 60 to 69 years of age. Family history of NIDDM was identified in 59.5% of
      the persons with the disease (CI 95%: 58.9 to 60.0) and in 26.3% of the healthy
      persons (CI 95%: 25.8 to 26.8). The low prevalence of NIDDM found in this study
      may be related to the low level of obesity in the population surveyed.

PMID- 9546081
TI  - [Enteroparasitoses in food handlers of the public schools in Uberlandia (Minas
      Gerais), Brazil].
AB  - A prospective study based on a parasitologic survey was carried out with a view
      toward controlling enteroparasitoses in food handlers who work in public primary
      schools in Uberlandia, Minas Gerais, Brazil. The study subjects were 264
      individuals from 57 schools, from whom three fecal samples (C) were collected: C1
      in September 1989, C2 in April 1990, and C3 in September 1990. The participants
      were predominantly female (259 women and 5 men) and ranged in age from 20 to 66
      years. A total of 792 samples were preserved in 10% formalin and analyzed using
      the method of Hoffman, Pons, and Janer. Intestinal parasites were found in 17%,
      10%, and 10% of the C1, C2, and C3 samples, respectively. The following organisms
      were found in C1: Giardia lamblia (8%), ancylostomids (6%), Ascaris lumbricoides
      (3%), Entamoeba histolytica (2%), Strongyloides stercoralis, Hymenolepis nana,
      Taenia sp., and Trichuris trichiura (less than 1% each). Parasites found in C2
      were: ancylostomids (5%), G. lamblia (2%), A. lumbricoides (1%), S. stercoralis,
      H. nana, Taenia sp., and Enterobius vermicularis (less than 1% each). In C3, the
      parasites observed were: ancylostomids (5%), G. lamblia (3%), A. lumbricoides
      (2%), S. stercoralis, and E. vermicularis (less than 1% each). After each
      collection, the individuals found to be infected received specific treatment. The
      authors recommend the establishment of epidemiologic surveillance through
      periodic parasitologic exams, specific treatment, and training on hygienic food
      handling and personal hygiene for all food handlers.

PMID- 9546082
TI  - [A combined methodology for understanding the duration of breast feeding the poor
      neighborhoods of Managua, Nicaragua].
AB  - This study examined the relationship of several maternal variables to the
      duration of exclusive breast-feeding and the total duration of breast-feeding,
      along with attitudes, perceptions, and beliefs about breast-feeding among women
      living in poor neighborhoods of Managua, Nicaragua. The field work was carried
      out in December 1992 and January 1993 using qualitative and quantitative methods.
      A structured questionnaire was administered in interviews with 556 mothers of
      children under 12 months of age, and meetings of four directed discussion groups
      were held, in which a total of 20 women participated. At one week of age, almost
      all the children of the mothers who were surveyed had been breast-fed, but only
      45% had been exclusively breast-fed. At 12 weeks old, 30% were already completely
      weaned. The discussion groups revealed the coexistence of positive opinions about
      both breast-feeding and bottle-feeding. However, exclusive breast-feeding was
      considered harmful for the mother, and breast milk was not thought to be
      sufficient nourishment for the child. Previous experience was strongly related to
      the duration of exclusive breast-feeding and to total breast-feeding duration.
      Attitudes, social support, and work situation were important factors influencing
      the total length of time women breast-fed a child. In general, the results
      obtained through the interviews and in the discussion groups were in agreement
      and showed that the elements needed to promote exclusive breast-feeding were
      social support, a favorable community environment, and policies that dealt with
      problems faced by working mothers. The complementary research methods were useful
      for obtaining information about the relative importance of different factors that
      determine the duration of breast-feeding and for understanding that practice in
      greater depth from the mother's point of view.

PMID- 9546083
TI  - Abdominal pain during pregnancy.
AB  - In evaluating the pregnant patient with abdominal pain, the physician is
      presented with a wide range of diagnostic possibilities, including disorders that
      can occur in nonpregnant individuals and disorders that are unique to pregnancy.
      The development of modern laboratory testing methods and diagnostic imaging
      techniques has led to a decline in the morbidity and mortality from many of these
      disorders. With an understanding of the physiologic changes occurring during
      pregnancy, a careful history and physical examination, and judicious use of
      laboratory tests and imaging studies, the physician should be able to determine
      the cause of the patient's pain in the great majority of cases and, in the words
      of Babler, avoid "the mortality of delay."

PMID- 9546084
TI  - The safety and efficacy of gastrointestinal endoscopy during pregnancy.
AB  - More than 12,000 pregnant patients in the United States per year have conditions
      normally evaluated by esophagogastroduodenoscopy (EGD). More than 6000 pregnant
      patient in the United States per year have conditions normally evaluated by
      sigmoidoscopy or colonoscopy. Endoscopy during pregnancy raises the unique issue
      of fetal safety, and endoscopic medications comprise a significant component of
      fetal risks from endoscopy. This article analyzes the safety of endoscopic
      medications during pregnancy, reviews the literature on the safety of
      gastrointestinal endoscopy during pregnancy, proposes guidelines for endoscopic
      indications during pregnancy, and describes modifications of gastrointestinal
      endoscopy during pregnancy to increase fetal and maternal safety.

PMID- 9546085
TI  - Gastrointestinal surgery during pregnancy.
AB  - Gastrointestinal surgical problems often mimic symptoms and signs of nonsurgical
      conditions that occur during pregnancy. This mimicry presents a particular
      challenge to diagnosis because avoiding a delay in treatment is critical to
      successful management. Some of these conditions, such as acute appendicitis and
      biliary colic, are common in younger women; however, the anatomic and physiologic
      changes of pregnancy can alter their usual manner of presentation. Many elective
      and urgent operations can be performed during pregnancy with minimal risk to the
      mother and fetus. The mother's condition should always take priority because her
      proper treatment usually benefits the fetus as well.

PMID- 9546086
TI  - Nutritional assessment and support during pregnancy.
AB  - Proper nutrition during pregnancy is critically important to mother and fetus.
      For most healthy women, the only nutritional intervention required may be
      adequate iron and folate intake; however, for others, who begin pregnancy in a
      malnourished state or whose nutritional intake deteriorates during pregnancy,
      invasive nutritional support, including tube feeding or parenteral nutrition, may
      be indicated. To guide nutritional therapy and to avoid its potential
      complications, it is necessary to evaluate the patient's nutritional state. Such
      evaluation must focus not only on body composition and substrate reserves but
      also on the patient's changing nutrient requirements and any impediments to the
      patient's capacity to ingest and assimilate food.

PMID- 9546087
TI  - Nausea and vomiting of pregnancy.
AB  - NVP is a spectrum of disorders ranging from the physiologically typical mild to
      moderate nausea and vomiting that is usually self-limited, to the pathologic,
      intractable symptoms of hyperemesis gravidarum that are associated with metabolic
      and electrolyte disturbances and weight loss. Up to 90% of pregnant women
      experience NVP. The pathogenesis remains poorly understood with multifactorial
      theories proposed combining both biologic and psychological factors. Diagnosing
      this syndrome is straightforward, but other organic sources should be excluded
      when symptoms are severe or prolonged. The overall prognosis is excellent for
      typical NVP, but whether hyperemesis gravidarum increases the risk to the fetus
      is controversial. Initial management should be conservative, including
      reassurance of the transient nature of the symptoms and the good prognosis, in
      addition to dietary modifications. Pharmacologic therapy is reserved for patients
      with persistent symptoms and is appropriate after discussion of the risks and
      benefits with informed consent. Alternative treatments, including psychotherapy
      and other nonpharmacologic modalities, are less proven but potentially safe and
      effective, thus providing additional therapeutic options. In refractory cases,
      nutritional supplementation becomes life-saving for both the mother and the
      fetus. Therapeutic abortion is a rare and last resort, to be used only when
      maternal life is threatened.

PMID- 9546088
TI  - Gastroesophageal reflux disease during pregnancy.
AB  - Pregnant patients with symptomatic GERD should be managed aggressively with
      lifestyle modification and dietary changes. Antacids and antacids/alginic acids
      combination or sucralfate should be considered first-line medical therapy. If
      symptoms are not adequately relieved or complications develop, treatment with
      cimetidine or ranitidine should be considered; these H2 receptor antagonists are
      preferred during pregnancy. Nizatidine cannot be recommended. Proton-pump
      inhibitors should be used with caution because little human experience is
      available. Despite this caveat, both proton-pump inhibitors are likely to be safe
      during pregnancy.

PMID- 9546089
TI  - Gastric and duodenal ulcers during pregnancy.
AB  - The frequency, symptoms, and complication rate of peptic ulcer disease appear to
      decrease during pregnancy significantly. Clinicians, however, often have to treat
      dyspepsia or pyrosis of undetermined cause because the frequency of pyrosis
      increases during pregnancy. Physicians are reluctant to perform
      esophagogastroduodenoscopy (EGD) during pregnancy for pyrosis to reliably
      differentiate gastroesophageal reflux from peptic ulcer disease. Dyspepsia or
      pyrosis during pregnancy first should be treated with dietary and lifestyle
      changes, together with antacids or sucralfate. When symptoms persist, H2 receptor
      antagonists are recommended. If symptoms continue and are severe despite these
      interventions, the patient should be evaluated for possible EGD or proton pump
      inhibitor therapy during the second or third trimester.

PMID- 9546090
TI  - Constipation and diarrhea in pregnancy.
AB  - Constipation and diarrhea are common during pregnancy, occurring in up to one
      third of women. Constipation is often the result of physiologic changes that
      occur during pregnancy, usually from hormonal effects on gastrointestinal
      motility. Diarrhea, on the other hand, is often caused by the same disorders
      responsible for diarrhea in the nonpregnant patient. The incidence,
      pathophysiology, evaluation, and treatment of constipation and diarrhea during
      pregnancy are reviewed in this article.

PMID- 9546091
TI  - Inflammatory bowel disease and pregnancy.
AB  - Despite the lack of prospective studies on the relationship between inflammatory
      bowel disease (IBD) and pregnancy, the evidence strongly supports the conclusions
      that fertility is compromised in active Crohn's disease; heredity plays an
      important role in type and location of disease; fetal outcome is essentially no
      different than in the general population, except in the presence of active
      Crohn's disease during pregnancy; and the course of IBD during pregnancy is
      influenced by disease activity or lack of it before pregnancy. The major
      influence on outcome of pregnancy, fetal outcome, and course of IBD is the
      favorable effect of drug therapy on the disease. Most drugs, including
      sulfasalazine, 5ASA products, corticosteroids, and immunosuppressives, are safe,
      certainly safer than permitting the disease to be active and allowing for the
      possibility of surgical intervention during pregnancy. Episiotomy is
      contraindicated in women with Crohn's disease and perirectal complications.
      Cesarean section probably is indicated in most patients with Crohn's disease with
      colonic involvement.

PMID- 9546092
TI  - Colon cancer during pregnancy. The gastroenterologist's perspective.
AB  - Colon cancer during pregnancy is uncommon but not rare, with an estimated
      incidence of several hundred cases per year in the United States. This type of
      cancer tends to have a poor prognosis that is attributable to delays in diagnosis
      and advanced disease at diagnosis. The diagnosis frequently is delayed because
      symptoms of colon cancer, such as rectal bleeding, nausea and vomiting, and
      constipation, often are attributed to normal pregnancy or minor complications of
      pregnancy. Pregnancy affects the diagnostic evaluation and therapy of colon
      cancer because of fetal risks of diagnostic tests and therapy. Appropriate
      medical evaluation of significant lower gastrointestinal complaints during
      pregnancy can lead to an earlier and improved diagnosis.

PMID- 9546093
TI  - Cancer of the colon, rectum, and anus during pregnancy. The surgeon's
      perspective.
AB  - Colorectal carcinoma presenting during pregnancy is uncommon. Most patients
      present late in pregnancy, and greater than 80% have rectal tumors. Pregnant
      patients with unexplained rectal bleeding should be evaluated by anorectal
      examination and flexible sigmoidoscopy. Treatment is individualized to each
      patient, but a strategy of proceeding immediately with a surgical resection when
      a diagnosis is made early in pregnancy and allowing the fetus to develop to safe
      delivery before treating when the diagnosis is made late in pregnancy is
      recommended. Most patients present with advanced tumors and have a poor
      prognosis, but prognosis by stage is not different from that in the general
      population. Adjuvant radiation and chemotherapy have limited roles in the
      treatment of pregnant women with colon and rectal carcinoma. Future challenges
      are aimed at improving survival through earlier diagnosis and the development of
      adjuvant therapies that are effective in patients with advanced disease.

PMID- 9546094
TI  - HIV in pregnancy.
AB  - Pregnancy in individuals infected with HIV has become an important problem
      because of a fourfold rise of infection in women of childbearing age in the
      developed world. The incidence of vertical transmission varies in different
      continents and is highest in Africa. Transmission may occur in utero
      (antepartum), during delivery (intrapartum), or after birth (postpartum),
      occurring during the latter period, in many cases, through breastfeeding.
      Maternal viral burden around the time of delivery is the strongest determinant of
      the risk of disease transmission. While breastfeeding may account for up to one
      third of cases of vertical transmission in Africa, the benefits of breastfeeding
      outweigh its risks, even in HIV infection, and breastfeeding is recommended in
      those areas. Treatment of the mother with antiretroviral agents significantly
      decreases the risk of vertical transmission.

PMID- 9546095
TI  - [Limits of exposure in the prevention of damage of reproduction: an operational
      proposal].
AB  - Recent studies have shown that the reproductive system may be particularly
      vulnerable to some environmental agents. This requires the definition of specific
      exposure limits to safeguard the reproductive health of both males and females
      and, not only of pregnant women. The paper presents such limits of exposure for a
      number of reproductive toxicants. These were defined on the basis of experimental
      and epidemiological evidence, taking into consideration the precautionary
      principle.

PMID- 9546096
TI  - Biological monitoring of acrylonitrile exposure.
AB  - This study reports the results obtained with the environmental and biological
      monitoring of 34 workers exposed to acrylonitrile (ACN). Occupational exposure
      was monitored during 8-h work shifts with both active and diffusive personal
      samplers which yielded comparable results. The median exposure was 78
      micrograms/m3. The ACN concentration in urine collected at the end of the work
      shifts correlated significantly with the environmental exposure. The ACN
      concentration in the pre-shift urine samples (median 3.6 micrograms/l) was lower
      than that found in the post-shift samples (median 10.9 micrograms/l), but higher
      than in the urine of non-exposed people (median 0.45 microgram/l). Smoking is an
      important confounding factor in monitoring exposure to ACN. The ACN concentration
      in urine provides reliable information about occupational and non-occupational
      exposure to ACN. Aspects of the mechanism of ACN excretion in urine are also
      discussed.

PMID- 9546097
TI  - [Risk of infection in a hospital environment].
AB  - The infectivologic risk in hospital environment. After a brief introduction on
      the historical development of the question of infectivologic risk in health
      services in general, and, in particular, in hospitals, the principal
      epidemiologic characteristics of viral hepatitis B and C, of HIV/AIDS and of TBC
      are examined as well as the potential cancerogenic role of the viral hepatitis.
      Guide-lines on staff health observation are also presented along with work
      fitness criteria.

PMID- 9546098
TI  - [An ergonomic study of postures of toll collectors].
AB  - The working activities of operators in the workstations along the italian motor
      ways involve repetitive movements of upper limbs and neck with asymmetric
      postures of the trunk. The tasks examined are characterized by factors
      potentially dangerous for developing musculo-skeletal disorders, such as
      repetitivity, and prolonged constrained postures. It is therefore crucial that
      dimensional and structural characteristics of the workplace are adequately
      designed, with regard to the anthropometric parameters and the type of activity
      performed. The results of our "on-site" investigation, using an observational
      method (OCRA), dedicated computerized modules for postural analysis (software
      "Vision 3000", Promatek, Ltd.), and recordings of myoelectrical activity (surface
      EMG) in the muscles of the shoulder girdle, have shown the need of a partial re
      designing of the man-workstation system under investigation.

PMID- 9546099
TI  - [Functional state and indications for a rehabilitation program of patients in a
      dialysis center: a multidisciplinary study with ergonomic, physiatrical and
      psychological evaluation].
AB  - The following study describes the functional status of the entire chronic
      hemodialysis ambulatory population in treatment at our center. The patients were
      evaluated from 3 points of view: ergonomic, phyiatric and psychological, thus
      going a snapshot picture in time of their status. Based on these three
      evaluations, the need for rehabilitation intervention was determined and
      rehabilitation treatment program was elaborated. The ergonomic evaluation
      determined the maximal sustained workload (MSW) from O2 consumption, minute
      ventilation, heart rate, subjective perception of fatigue and dyspnea. The
      phyiatric examination included a thorough musculoskeletal examination,
      application of a functional ability instruments (Karnofsky + FIM) and then
      integrated the results with the ergonomic + psychologic testing in order to
      generate phyiatric prescription. The psychologist had a conversation with all
      patients and applied 2 instruments for evaluation of health-related quality of
      life (CBA-H + SIP). The results of these studies indicated a markedly compromised
      aerobic capacity, which worsened with age in years rather than with years in
      dialysis. Phyiatric prescription were considered necessary in 78% of the patients
      with major goals being re-conditioning and joint mobilization in order to
      diminish the fragility of independence in this population. The psychological arm
      of the study revealed good adaptation to chronic dialysis in 75% of the
      population, with however absorption of a passive lifestyle. The remaining 25% of
      the population showed severe psychological distress and social withdrawal.
      Psychological support for this population is necessary to identify families at
      risk for stress and poor adaptability as well as to help motivate patients who
      require rehabilitation to participate in therapy.

PMID- 9546100
TI  - [Evaluation of the capacity of work using upper limbs after radical latero
      cervical surgery].
AB  - Evaluation of arm work capacity after radical neck surgery. The aim of this paper
      is to describe an approach for the assessment of work capacity in patients who
      underwent radical neck surgery, including those treated with radiation therapy.
      Nine male patients, who underwent radical neck surgery 2 months before being
      referred to our Unit, participated in the study. In addition to manual muscle
      strength test, we performed the following functional evaluations: 0-100 Constant
      scale for shoulder function; maximal shoulder strength in adduction/abduction and
      intrarotation/extrarotation; instrumental. We measured maximal isokinetic
      strength (10 repetitions) with a computerized dynamometer (Lido WorkSET) set at
      100 degrees/sec. During the rehabilitation phase, the patients' mechanical
      parameters, the perception of effort, pain or discomfort, and the range of
      movement were monitored while performing daily/occupational task individually
      chosen on the simulator (Lido WorkSET) under isotonic conditions. On this basis,
      patients were encouraged to return to levels of daily physical activities
      compatible with the individual tolerable work load. The second evaluation at 2
      month confirmed that the integrated rehabilitation protocol successfully
      increased patients' capacities and "trust" in their physical capacity. According
      to the literature, the use of isokinetic and isotonic exercise programs appears
      to decrease shoulder rehabilitation time. In our experience an excellent
      compliance has been noted. One of the advantages of the method proposed is to
      provide quantitative reports of the functional capacity and therefore to
      facilitate return-to-work of patients who underwent radical neck surgery.

PMID- 9546101
TI  - The biological monitoring of inhalation anaesthetics.
AB  - The biological monitoring of inhalation anaesthetics. Occupational exposure to
      inhalation anaesthetics is an undesired consequence of the work in the operating
      theatre. Anaesthesia is currently practised using nitrous oxide associated with
      one or more potent anaesthetics (halothane, enflurane, isoflurane). In the
      present study we evaluated the occupational exposure to inhalation anaesthetics
      during anaesthesia in 190 operating theatres of 41 hospitals in Italy. Nitrous
      oxide, halothane, enflurane, isoflurane were detected in the urine of 1521
      exposed subjects (anaesthetists, surgeons and nurses). Significant correlations
      were found between the anaesthetic concentrations in urine produced during the
      shift (Cu) and anaesthetic environmental concentrations (CI). The results show
      that the urinary anaesthetic concentration can be used as an appropriate
      biological exposure index. The biological threshold values (urinary concentration
      values) proposed are the following: nitrous oxide, 15, 28 and 57 micrograms/L for
      an environmental exposure of 25, 50 and 100 ppm respectively; halothane, 97
      micrograms/L (for an environmental exposure of 50 ppm), 6.1 micrograms/L (for an
      environmental exposure of 2 ppm) and 3.3 micrograms/L (for an environmental
      exposure of 0.5 ppm); enflurane, 145 micrograms/L (for an environmental exposure
      of 50 ppm), 22.7 micrograms/L (for an environmental exposure of 10 ppm), 3.7
      micrograms/L (for an environmental exposure of 1 ppm); isoflurane, 5.3
      micrograms/L (for an environmental exposure of 2 ppm) and 1.8 micrograms/L (for
      an environmental exposure of 0.5 ppm). These values apply to urine samples
      collected at the end of 4-hours' exposure to the anaesthetics.

PMID- 9546102
TI  - Analysis of growth rate of pediatric kidneys transplanted into juveniles or
      adults.
AB  - Estimation of renal length was carried out during radionuclide function studies,
      in cases of pediatric kidneys transplanted into adolescents or adults. In all 24
      cases of single kidney transplants, the kidneys eventually increased in size, but
      at varying rates. From 5 cases with repeat studies close in time, and shortly
      after transplantation, an apparent maximal growth rate was estimated. In 3 pairs
      of dual renal transplants, with both kidneys surviving, marked differences in
      growth of each member of the pair was noted. The present initial description, of
      rates of change in size of the transplanted pediatric kidneys, may serve as a
      baseline from which to sort out the contributions of pre- and post-transplant
      factors.

PMID- 9546103
TI  - Late embryonic and early posthatch growth of heart and lung in White Leghorn
      lines of chickens.
AB  - Growth and development of heart and lungs were measured from day 15 of incubation
      to 25 days after hatch in lines of chickens that had undergone long-term
      selection for high (HAS) or low (LAS) antibody titers to sheep erythrocytes. A
      correlated response to this selection was heavier 28-day body weights for LAS
      than HAS chickens. In this experiment body weights were heavier in line LAS than
      HAS from 15 days of incubation to 5 days after hatch and again at 25 days after
      hatch. Absorption of residual yolk was greater in HAS than LAS chicks. Although
      there were no differences between lines for absolute heart weights, lungs were
      heavier in line LAS than HAS at all ages except 20 days after hatch. Relative to
      body weight, both heart and lung weights declined with age, however, the pattern
      of decline differed. For this criterium, hearts were larger in line HAS than LAS
      to 5 days after hatch with no difference thereafter; for lungs lines were similar
      until 5 days after hatch after which they were larger in LAS than HAS chicks. In
      all but one case (HAS at hatch) the left:right relationship for lung weights
      exhibited fluctuating asymmetry with the left minus right character difference
      having a normal distribution and mean zero. The degree of fluctuating asymmetry,
      however, varied with age.

PMID- 9546104
TI  - Ontogenetic limb bone scaling in basic fibroblast growth factor (FGF-2)
      transgenic mice.
AB  - Basic fibroblast growth factor (FGF-2) is a potent mitogen which is required for
      normal development, particularly the development of the skeletal system, where
      the inhibition of FGF binding to its receptor results in various skeletal
      malformations. The present study employed a newly engineered line of FGF-2
      transgenic mice to determine the effects of overexpressing FGF-2 on limb bone
      ontogeny. We collected radiographic and weight data longitudinally and obtained
      the length, proximal, distal, and minimum diaphyseal widths of the humerus,
      femur, and tibia. Because growth is nonlinear with respect to time, we used the
      Gompertz mathematical model to obtain parameters describing rate and timing for
      each individual for each measurement. Differences in the parameters due to
      genotype and sex were subsequently tested with ANOVA. Transgenic animals
      exhibited consistently shorter limb bones which were generally wider at the
      epiphyses than those of controls. Parameters of early growth, including initial
      size and proportional rate of growth, appeared to be most directly responsible
      for significant differences in final size; however, exponential decay of growth
      was also a marginally significant factor. There were no differences between the
      genotypes in body weight, indicating that the shape anomalies observed in
      transgenic mice were a direct result of the action of FGF-2 rather than a general
      runting phenomenon.

PMID- 9546105
TI  - Variability of embryonic development among three inbred strains of mice.
AB  - We examined the relationships between litter size, embryonic growth, days of
      gestation, onset and duration of morphological stages and development of the
      first arch skeleton in three inbred strains of mice--C57BL/6, CBA/J and C3H/He.
      Detailed embryonic staging was based on craniofacial development between 11 and
      18 days of gestation. Considerable intra- and interlitter variation of
      morphological stages of embryonic development exists in all three inbred strains.
      The relationship of morphological stages to days of gestation reveals that each
      stage has a different duration, being shortest at Theiler's stage 18 and longest
      at stage 21 in all three inbred strains. Embryos of CBA/J mice tend to reach each
      stage later than do embryos of the other two strains, i.e., morphological
      development is slowest in CBA/J. The greatest length, a measurement of embryonic
      growth, increases at a constant rate during gestation in all three strains. In
      C57BL/6 and CBA/J, more embryos tend to be implanted in the right horn of the
      uterus than in the left, whereas in C3H/He an even number of embryos tends to be
      implanted in both horns. Timing of the development of Meckel's cartilage differs
      between the three inbred strains: both condensation and onset of matrix
      deposition begin one stage earlier in C57BL/6 than in CBA/J and C3H/He. On the
      other hand, alkaline phosphatase, one of the earliest markers for bone
      development, is expressed at the same time in all three inbred strains.
      Differences in timing of skeletal development between the strains may be
      attributed in part to the genealogical closeness OF CBA/J and C3H/He mice.

PMID- 9546106
TI  - 6R-L-erythro-5,6,7,8-tetrahydrobiopterin is involved in brain vulnerability of
      senescence-accelerated mouse during the processes of aging.
AB  - The effects of age on the dopamine (DA) turnover and 6R-L-erythro-5,6,7,8
      tetrahydrobiopterin (6R-BH4), a cofactor for monooxygenases, were investigated in
      the striatum and midbrain of the senescence accelerated mouse (SAM) at 6, 12 and
      15 months old. 6R-BH4 and DA levels were decreased significantly in the striatum
      of 15-month-old SAM-P/1 (senescence accelerated prone) mice. At 12 months old, DA
      level was decreased significantly in the striatum of SAM-P/1 compared with SAM
      R/1 (senescence accelerated resistant) mice. The reduction of striatal DA level
      was shown to be related to the depletion of 6R-BH4 in the striatum during the
      processes of aging. Age-related decreases in striatal dopamine function occurred
      in SAM-P/1 mice earlier than in the SAM-R/1 mice. The striatal [DOPAC]/[DA]
      ratio, as the index of DA turnover, was increased significantly in the 15-month
      old SAM-P/1 mice. On the other hand, the DA, 6R-BH4 levels and the ratio of
      [DOPAC]/[DA] did not show any changes in the midbrain of SAM-P/1 and SAM-R/1
      during the processes of aging. It was suggested that brain vulnerability with
      aging may be associated with the levels of 6R-BH4.

PMID- 9546107
TI  - Animal models showing "accelerated aging" are more likely to be useful for
      pathology than for mechanisms of aging.

PMID- 9546108
TI  - Body composition of inactivated growth hormone (oMt1a-oGH) transgenic mice:
      generation of an obese phenotype.
AB  - The consequences of a 42 d exposure to elevated growth hormone (GH) on adipose
      tissue were assessed using the regulatable ovine metallothionein- ovine GH (oMt1a
      oGH) transgene in male and female GH transgenic (TG) mice. Activation of
      transgene expression at 21 d of age followed by inactivation of transgene
      expression at 63 d of age (TG-on/off) increased individual white adipose tissue
      (WAT) depots and total body lipid stores in both males and females. WAT,
      expressed as a percentage of fasted body weight, did not differ in wildtype (WT)
      and continuously activated TG males and females up to 105 d of age, but was
      increased approximately 270% following inactivation of the transgene. Inguinal
      depot adipocytes were more numerous in both male and female TG +/- relative to WT
      or TG animals. The ensuring obesity was not accompanied by a decrease in
      thermogenic capacity of brown adipose tissue, as indexed by uncoupling protein
      quantity. GH transgene expression was accompanied by elevated insulin levels that
      were restored to WT levels upon cessation of transgene expression (p > 0.1).
      Early, transient exposure to elevated GH increased total body lipid by nearly
      threefold independent of gender; the increased lipid content was sustained and
      reflected WAT hypertrophy and hyperplasia. The oMt1a-oGH mouse provides a novel
      model of induced obesity in response to inactivation of a GH-transgene by the
      withdrawal of the transgene stimulus.

PMID- 9546109
TI  - Whole body bone resorption in the growing pig.
AB  - Our knowledge of total body bone resorption during growth is limited. The primary
      purpose of this study was to determine if a commercially available bone
      resorption assay, developed for measuring human bone resorption, could be used to
      measure whole body bone resorption in young, growing pigs. A secondary purpose
      was to evaluate if this method could detect changes in bone resorption in
      response to certain dental appliances which have been shown to change mandibular
      and maxillary growth. Five growing 4-month-old male Hanford minipigs (Sus scrofa)
      were housed in metabolic cages for 24 h, every other day, over a period of 1
      month. Three of the animals were fitted with a mandibular protrusive orthodontic
      appliance. Total 24 h urines were collected in which the concentration of
      creatinine and collagen type I N-telopeptide crosslinks (NTx, a marker of bone
      resorption) were measured. The NTx immunoassay was originally developed for the
      analysis of human urine. Pig bone was powdered, defatted, and decalcified, and
      the resulting powder digested with bacterial collagenase. The digest was screened
      for NTx content, in the same fashion as the pig urines. Bone extract and pig
      urines were cross-calibrated to a standard of adolescent human urine. This
      allowed calculation of the daily quantity of pig bone resorbed. Daily metabolite
      excretion was quite variable in these growing animals; for NTx the CV was 31%,
      for creatinine the CV was 25%. The mean daily quantities of bone resorption
      ranged between 26 and 46 grams of bone which amounted to 1.2-1.7% of estimated
      total skeletal mass. The protrusive appliances increased bone resorption
      significantly during the first two weeks of the trial. IN CONCLUSION: the NTx
      assay can be used to measure bone resorption in pigs; the assay is sensitive
      enough to indicate changes in bone resorption, such as those caused by an
      orthodontic mandibular protrusive appliance. During growth, bone resorption
      varies greatly from day to day. On average, every 24 h, 1.4% of the skeletal mass
      is resorbed.

PMID- 9546110
TI  - Localization and treatment of an oxidation-sensitive defect within the TCR
      coupled signalling pathway that is associated with normal and premature
      immunologic aging.
AB  - The age-dependent decline in the ability of T-cells to mount a proliferative
      response both to mitogens and to receptor ligation is due to an age-related
      defect in signal transduction, since functional expression of receptors displayed
      by aged T-cells is not reduced. We show here that, although turnover of
      phosphatidylinositol is not diminished, total inositol-trisphosphate generation
      decreases after T-cell receptor (TCR) ligation, resulting in reduced flux of
      calcium. Defective inositol-trisphosphate generation may result from impaired
      activation of phospholipase C due to decreased tyrosine phosphorylation of this
      enzyme after ligation of CD3 in aged cells. Proliferation of aged T-cells, which
      is normally 10-30% of the level of young controls, was enhanced almost tenfold by
      glutathione or its precursor N-acetyl L-cysteine (NAC), reached levels of young
      controls and was accompanied by restoration of normal inositol-trisphosphate
      generation and calcium flux. These findings suggest that the T-cell antigen
      receptor is associated with at least two types of signal transduction modules.
      The first depends on synthesis and phosphorylation of phosphatidylinositol that
      is independent of sulphydryl groups and is not affected by senescence. The second
      transduction module includes tyrosine phosphorylation and activation of
      phospholipase C. This module is regulated by glutathione levels and is diminished
      in aged T-cells, that are deficient in reducing equivalents which support the PLC
      gamma-dependent generation of inositol-trisphosphate from phosphatidylinositol
      derivatives. This underlying biochemical defect also occurs earlier in strains
      which display premature aging due to differences in the H-2 region of MHC I.

PMID- 9546111
TI  - How do practicing clinicians manage Helicobacter pylori-related gastrointestinal
      diseases in Germany? A survey of gastroenterologists and family practitioners.
AB  - BACKGROUND: Since the bacterium H. pylori was identified in 1982, overwhelming
      evidence has implicated it as the causal factor in the occurrence and relapse of
      peptic ulcer disease. The major objective of this study was to examine the extent
      to which physicians recognize H. pylori as a causal agent in peptic ulcer disease
      or as potential cofactor in other gastrointestinal diseases, and the extent to
      which this knowledge has influenced diagnostic and therapeutic practices.
      MATERIALS AND METHODS: Using a national mail survey in Germany in September 1995,
      1197 family practitioners and 1197 gastroenterologists were selected for the
      study. RESULTS: Of the surveyed physicians, 756 (32%) responded. Family
      practitioners treated almost 50% of their patients with initial presentation of
      suspected ulcer disease without ordering further diagnostic tests. More than 25%
      of the family practitioners and 14% of the gastroenterologists reported that they
      do not treat diagnosed H. pylori infection in the first presentation of duodenal
      ulcer. At the time we conducted the study, 22% of responding family practitioners
      and 5% of responding gastroenterologists treated the first presentation of H.
      pylori-positive ulcer disease with regimens determined to be ineffective
      according to the available literature. CONCLUSIONS: Gastroenterologists preferred
      to treat H. pylori infection when the associated disease was one for which a
      causal relationship had been more clearly established, while family practitioners
      showed less discrimination. In order to provide optimal therapy aimed at
      minimizing the course and consequences of H. pylori-related diseases, researchers
      in the field must ensure continuous dissemination of current knowledge.

PMID- 9546112
TI  - Comparison of Helicobacter pylori infection between Fukuoka, Japan and Chinju,
      Korea.
AB  - BACKGROUND: Helicobacter pylori is the causative agent of type B chronic
      gastritis, and plays a major role in the pathogenesis of gastroduodenal ulcer and
      gastric cancer. Because gastric cancer has been the leading cause of cancer
      mortality in Japan and Korea, we conducted a seroepidemiological study to
      estimate the prevalence of H. pylori infection in Japan and Korea in order to
      explain the current change in the gastric cancer incidences between two
      countries. MATERIALS AND METHODS: Samples used for this study included 1204 sera
      from Chinju, Korea and 580 sera from Fukuoka, Japan. Immunoblotting, using a
      sonicated crude H. pylori antigen and 1:5 dilution of serum, was performed,
      considering the immunoblot shows reactivity to the 120 Kd antigen of H. pylori as
      a specific marker of H. pylori infection. RESULTS: Seroepidemiology data from
      Fukuoka, Japan showed a prevalence of H. pylori infection of 20% before school
      age, 40% by teenage years, and over 80% beyond 20 years of age. Seroepidemiology
      data from Chinju, Korea, showed a 50% infection rate in preschool ages, and over
      80% prevalence rate after 7 years of age. CONCLUSIONS: Lower rates of childhood
      H. pylori infection in Fukuoka may explain the recent decline and shift in the
      incidence of stomach cancer in Japan, supporting the hypothesis that H. pylori is
      a major determinant in the pathogenesis of stomach cancer.

PMID- 9546113
TI  - Serologic detection of CagA positive Helicobacter pylori infection in a northern
      Italian population: its association with peptic ulcer disease.
AB  - BACKGROUND: About 60-70% of Helicobacter pylori strains possess cagA (cytotoxin
      associated gene A) gene and express its product CagA, a highly immunogenic 128
      140 kD protein. Patients infected with CagA positive strains develop serum IgG
      anti-CagA. A serologic response to CagA has been detected in Helicobacter pylori
      infected patients with peptic ulcer more frequently than in those with gastritis
      alone. It is nuclear whether this finding is consistent in different geographical
      populations. We investigated the relationship between anti-CagA seropositivity
      and peptic ulcer disease in a Northern Italian population. MATERIALS AND METHODS:
      We studied 135 H. pylori infected patients: 65 with duodenal ulcer (DU), 28 with
      gastric ulcer (GU) and 42 with non ulcer dyspepsia (NUD). Sera from these
      patients were assayed by EIA (enzyme immunoassay) for anti-CagA IgG. RESULTS: A
      high prevalence of anti-CagA was found associated with DU (86.1%) and GU (96.4%),
      while NUD patients showed anti-CagA seropositivity of 52.4% (Odd ratio, 5.66; 95%
      confidence interval, 2.23 to 14.32; p < .001, DU vs. NUD; Odd ratio, 24.5; 95%
      confidence interval, 3.05 to 197.6; p = .003, GU vs. NUD). DU patients showed
      anti-CagA seropositivity titer (1.15 (0.61 OD, mean (SD) higher than that of NUD
      patients (0.78 (0.60 OD, mean (SD) (p < .05). CONCLUSIONS: These data demonstrate
      in a Northern Italian population that anti-CagA seropositivity is strongly
      associated with peptic ulcer disease and suggest that CagA might play an
      important role in ulcer pathogenesis.

PMID- 9546114
TI  - Growth inhibitory and bactericidal activities of lansoprazole compared with those
      of omeprazole and pantoprazole against Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori plays a role in the pathogenesis of both duodenal
      and gastric ulcers. The aim of this study was to evaluate the effect of the
      proton pump inhibitor (PPI), lansoprazole, commonly used in eradication regimens,
      on growth, bactericidal activity and morphology of H. pylori in vitro in
      comparison with other PPIs. MATERIALS AND METHODS: Growth inhibitory activity of
      each of the PPIs was evaluated by determining minimum inhibitory concentrations
      using an agar dilution method. Bactericidal activity was determined by analysis
      of the viable cells in culture at various time points after incubation with
      different concentrations of the PPIs. Bacterial morphology was examined using
      scanning electron microscopy of fixed cells after exposure to the test
      substances. Urease activity in cell extracts of H. pylori that had been incubated
      with increasing concentrations of the PPIs was determined by colorimetry.
      RESULTS: The growth inhibitory activity of lansoprazole was significantly more
      potent than that of omeprazole or pantoprazole (MIC90 6.25 vs. 25 and 100
      micrograms/ml, respectively). Exposure of H. pylori to lansoprazole produced loss
      of viability and an aberrant bacterial morphology, which was more extensive than
      seen with omeprazole or pantoprazole. Lansoprazole dose dependently inhibited
      urease activity; its effectiveness was comparable with omeprazole but more potent
      than pantoprazole. CONCLUSIONS: The mechanism of action that leads to loss of
      viability of H. pylori cells appears to differ between the three PPIs
      investigated; lansoprazole was the most potent of the three agents in terms of
      growth inhibition and disruption of bacterial morphology.

PMID- 9546115
TI  - An investigation of the molecular basis of the spontaneous occurrence of a
      catalase-negative phenotype in Helicobacter pylori.
AB  - BACKGROUND: The discovery of a highly active catalase in Helicobacter pylori that
      in some strains may lose its activity has generated strong scientific interest.
      We have characterized a spontaneous catalase-negative isolate of H. pylori (UNSW
      RU1) and sequenced katA in the parent strain and the promoters of both phenotypes
      as a prelude to understanding the genetic processes leading to the failure to
      express catalase. MATERIALS AND METHODS: Protein extracts from both phenotypes
      were examined for catalase on 2D-PAGE and analyzed by Western blot-based immuno
      analysis. Presence of catalase mRNA was detected by Northern blot. Hi-Fidelity
      PCR was used to sequence the katA promoter while katA was sequenced using cycle
      sequencing. The transcription start site was located by primer extension.
      RESULTS: Catalase protein was absent in UNSW-RU1 (KatA-) by 2D-PAGE and Western
      blot, as was catalase mRNA by Northern blot, indicating that the cause of the
      KatA- phenotype was at the level of transcription. No mutations were found in the
      promoter region of the KatA- isolate. The transcription start site was identified
      55 bp upstream of the ATG site and putative RNA polymerase binding sites were
      mapped at "-10" and "-35". A Fur box was identified 181 bp upstream of the
      transcription start site. The sequences of an 876 bp ORF and a 366 bp Escherichia
      coli phnA homologue were identified. CONCLUSIONS: The UNSW-RU1 (KatA-) phenotype
      does not express KatA or transcribe katA. The absence of defects in its promoter
      and a large part of its ORF indicates that loss of activity may be due to a
      mutation in an accessory gene essential for catalase expression, or to the
      binding of a repressor preventing katA transcription.

PMID- 9546116
TI  - Follow-up of Helicobacter pylori positive gastritis and argyrophil cells pattern
      during the natural course of gastric ulcer.
AB  - BACKGROUND: A follow-up of argyrophil cell hyperplasia in Helicobacter pylori
      positive corpus gastritis in gastric ulcer patients during the natural course of
      ulcer disease. METHODS: Endoscopic biopsies (4 specimens) were obtained step-wise
      from the posterior wall of the corpus mucosa in 55 gastric ulcer (GU) patients.
      The natural course of GU was followed up in 38 patients during more than 10 years
      (maximum 19 years), and altogether 115 endoscopic examinations were made: 20
      patients were re-examined once, 14 twice, and 4 three times. A total of 364
      biopsies from 307 biopsy sites were stained by Grimelius' silver, hematoxylin
      eosin, and Giemsa method for the analysis of the argyrophil endocrine cells,
      chronic gastritis, and H. pylori colonization, respectively, according to the
      Sydney System. RESULTS: Of 307 biopsy sites, 153 (50%) showed some grade of ACH.
      Focal (linear/micronodular) hyperplasia was found in 118 (77%) of biopsy sites;
      it was detected in 78 (66%) cases of atrophic corpus mucosa, but was present in
      only 14 (12%) cases of gastritis without atrophy or in the normal mucosa. In the
      follow-up patients, ACH evolved in 17 and progressed in 6 cases, and a
      simultaneous development of atrophic corpus gastritis was found in 20 cases.
      CONCLUSION: This study demonstrates that ACH evolves during the natural course of
      GU, alongside the development of chronic atrophic gastritis.

PMID- 9546117
TI  - A modified McMullen's staining for Helicobacter pylori: a high-contrast, visibly
      prominent method.
AB  - BACKGROUND: Many stains can be used for the histological assessment of
      Helicobacter pylori, but all have defects from the standpoint of sensitivity,
      convenience, stability, visible prominence and cost. This paper describes a stain
      which produces satisfactory results on all the above accounts. MATERIALS AND
      METHODS: Paraffin-embedded sections were dewaxed and treated with 0.2% w/v carbol
      fuchsin for two min; then 1.0% w/v malachite green was applied for two minutes.
      RESULTS: This technique stained the bacterial from a deep magenta against a light
      green background. The characteristic morphology of H. pylori was identified very
      easily as a stumpy curved rod, and the coccoid forms were also identified.
      Staining was not specific with mixed samples of bacteria, but it was sufficient
      to identify H. pylori in the gastric mucosa. CONCLUSION: We have established an
      easy, stable, convenient, low-cost, and easily recognizable staining method for
      H. pylori in paraffin-embedded tissue.

PMID- 9546118
TI  - The UBiT-100 13CO2 infrared analyzer: comparison between infrared spectrometric
      analysis and mass spectrometric analysis.
AB  - BACKGROUND: Although the 13C-urea breath test is the most accurate noninvasive
      method for detecting the presence of H. pylori infection, the requirement for an
      expensive mass spectrometer to analyze breath samples has prevented physicians
      from providing rapid results near the patient. Recently, a new type of infrared
      spectrometric analyzer, the UBiT-100, was developed for analyzing 13CO2 in
      breath. The purpose of this study is to compare results analyzed by the UBiT-100
      to those analyzed by the mass spectrometric method. METHODS: Four hundred and
      fifty-three subjects participated in this study. Breath samples were collected
      before administration of 100 mg of 13C-urea and at 10, 20, 30, 45 and 60 min
      after administration. Subjects were asked to hold their breath for 10 sec and
      then exhale in order to collect breath samples containing more than a 2%
      concentration of CO2. Samples were then analyzed by both methods. RESULTS: The
      correlation analysis using values at 20 min after the administration of the study
      drug (433 points) was excellent with the regression equation of Y = 1.034x -
      0.203; r = .996. The results of the UBiT-100 were available in 6 min, making the
      entire testing procedure less than 30 min. CONCLUSIONS: The UBiT-100 infrared
      analyzer provides a simple and accurate method of performing the urea breath test
      while the patient is still in the doctor's office.

PMID- 9546119
TI  - Amoxicillin/metronidazole/omeprazole/clarithromycin: a new, short quadruple
      therapy for Helicobacter pylori eradication.
AB  - BACKGROUND: Triple therapy regimens including two antibiotics plus acid
      suppression have become the new standard therapy in Helicobacter pylori
      eradication because of success rates of about 90%. However, these regimens are
      still costly, duration is about one week or less, and side-effects are not
      negligible. We therefore evaluated a new quadruple therapy, because theoretically
      a shorter duration of treatment may result in reduced costs, fewer side-effects,
      and possibly in a lower potential for antibiotic resistances. METHODS:
      Controlled, prospective pilot study including H. pylori-positive patients with
      gastric or duodenal ulcers or erosive gastritis, treated after failure of dual
      therapy (proton-pump-inhibitors or ranitidine plus amoxicillin) or for the first
      time. They were assigned to a one week triple standard therapy, consisting of
      metronidazole 400 mg bid + omeprazole 20 mg bid + clarithromycin 250 mg bid, or a
      newly created quadruple-regimen, which adds amoxicillin (1 g bid) to the above
      triple regimen. Each of the four drugs was given for 5 days. H. pylori status was
      checked by 13C urea breath test before and after four weeks of therapy. RESULTS:
      A total of 71 patients were treated by quadruple therapy, and 42 patients were
      treated by triple therapy. The eradication rate of H. pylori for patients under
      quadruple treatment, without vs. with previous dual therapy, were 96% vs. 92%
      (42/44 vs. 22/24) by per protocol and 91% vs. 88% (42/46 vs. 22/25) by intention
      to treat analysis (comparisons not significant). No major side-effects were
      reported. CONCLUSIONS: Five-day quadruple therapy (with omeprazole,
      metronidazole, clarithromycin and amoxicillin) represents an effective and safe
      new regimen for H. pylori eradication.

PMID- 9546120
TI  - Assessment of a new triple agent regimen for the eradication of Helicobacter
      pylori and the nature of H. pylori resistance to this therapy in Japan.
AB  - BACKGROUND: Multiple regimens for the eradication of Helicobacter pylori have
      been tested, but the best therapy has not been determined yet. To determine the
      efficacy of a new triple agent regimen using a combination of lansoprazole,
      amoxicillin, and clarithromycin against Helicobacter pylori (H. pylori), and to
      examine H. pylori resistance to this therapy in ineffective cases. METHODS: We
      studied a total of 71 patients infected with H. pylori who had gastric ulcer (n =
      37) or duodenal ulcer (n = 34) as confirmed by endoscopy. Patients received 1500
      mg amoxicillin, 400 mg clarithromycin and 30 mg lansoprazole for 2 weeks followed
      by 30 mg lansoprazole for 6 weeks in patients with gastric ulcer or for 4 weeks
      in those with duodenal ulcer. Endoscopic examination was performed before
      treatment and at 1 month, 2 months, and 5 months after initiating treatment to
      check the status of ulceration and H. pylori infection. RESULTS: The eradication
      rate of H. pylori was 92% (CI, 83-100%) in the gastric ulcer group and 94% (CI,
      86-100%) in the duodenal ulcer group at 5 months, as determined by per-protocol
      analysis. Resistance to clarithromycin was present in 1 of 71 (1%) patients
      before treatment and in 2 of 5 (40%) patients after treatment. No resistance to
      amoxicillin and lansoprazole was found in patients before or after treatment. The
      resistance to clarithromycin changed during the observation period. CONCLUSIONS:
      The new triple agent regimen was effective against H. pylori. Resistance to
      clarithromycin may not be permanent and it might be one of the risk factors which
      affect the efficacy of a clarithromycin-based therapy.

PMID- 9546121
TI  - The serum 13C-bicarbonate assay: a replacement for urea breath tests?

PMID- 9546122
TI  - Vector potential of houseflies (Musca domestica) for Helicobacter pylori.

PMID- 9546123
TI  - [Imaging studies of excretory urography and computed tomography scan for patients
      suffering from renal colic].
AB  - Renal colic mainly due to urolithiasis is one of the most common morbid
      conditions in urology and commonly seen in the urology emergency clinic. Imaging
      studies were performed to evaluate the upper urinary tract of 29 patients
      suffering from renal colic in the 2 years between November, 1994 and October,
      1996. After intramuscular injection of the analgesic (pentazocine, 15 mg), all 29
      patients were examined by excretory urography (IVP) at the time of the first
      visit. In some patients abdominal plain computed tomography (CT) scan was
      performed consecutively even when extravasation of the contrast medium was not
      seen. Spontaneous peripelvic extravasation was seen in 14 patients (11 males and
      3 females) with urolithiasis; 7 of them were diagnosed by IVP, 5 by IVP plus CT
      scan and 2 with CT scan only. IVP imaging study followed by plain abdominal CT
      scan is useful even when the contrast medium is not extravasated on IVP in
      patients suffering from renal colic.

PMID- 9546124
TI  - [Clinical study on 17 cases of genitourinary tuberculosis].
AB  - Between 1987 and 1995, 17 patients with genitourinary tuberculosis were treated
      at Iwate Prefectural Central Hospital. The incidence of newly diagnosed
      genitourinary tuberculosis was 17 out of 16,363 outpatients (0.1%) during the 9
      year period. Twelve patients had urinary tuberculosis and genital as well as
      urinary organs were affected in 5. Six (35%) patients presented in their fifties
      and 5 (29%) each in their forties and sixties. Nine (53%) patients had irritative
      voiding symptoms as the chief complaint. Only 29% had a known history of extra
      genitourinaty tuberculosis. In addition to the standard multidrug chemotherapy,
      nephrectomy was performed in 5 patients and orchiectomy in 2 with epididymal
      tuberculosis. The incidence of tuberculosis has recently increased in many parts
      of our country and more attention should be paid to genitourinary tuberculosis.

PMID- 9546125
TI  - [PSA-doubling time immediately before the diagnosis of prostate cancer].
AB  - PSA-doubling time (PSA-DT) immediately before the diagnosis of prostate cancer
      was calculated in 8 prostate cancer patients in whom PSA was checked three or
      more times with the same kit during a period of 6 months or more. The correlation
      between PSA-DT and clinical stage or pathological differentiation was analyzed.
      In most patients, PSA correlated well showing a straight regression line to the
      observation period on a hemi-logarithmic scale. The correlation coefficient was
      high, almost 0.9 or more except in one patient. PSA-DT ranged from 5.1 to 64.9
      months, averaging 23.1 months. There was no significant correlation between
      clinical stage or pathological differentiation and PSA-DT. However, PSA-DT in
      stage D patients tended to be shorter than that of stage B + C patients. One
      patient who had stage D poorly differentiated carcinoma died of cancer
      recurrence. In this patient, PSA-DT was short (5.1 months).

PMID- 9546126
TI  - [A case of renal cell carcinoma with synchronous contralateral adrenal
      metastasis].
AB  - A 73-year-old female visited our department with right incidentally-found renal
      tumor, which was revealed by follow-up computed tomography (CT) on an annual
      physical check-up. CT also showed a left adrenal mass that was 4 cm. Further
      evaluation suggested right renal cell carcinoma and left adrenal metastasis. The
      patient, therefore, underwent right-adrenal-gland-sparing radical nephrectomy and
      left adrenalectomy. The pathology report indicated renal cell carcinoma with
      contralateral adrenal metastasis. A case of contralateral adrenal metastasis from
      renal cell carcinoma is not common clinically. Furthermore, whether ipsilateral
      adrenalectomy should be performed in such a case is still controversial at this
      stage.

PMID- 9546127
TI  - [Renal cell carcinoma detected by metastasis to the frontal sinus: a case
      report].
AB  - A 58-year-old man was admitted with a swelling in the frontal region.
      Computerized tomography scan, magnetic resonance imaging and angiography revealed
      a tumor in the right frontal sinus. The surgically extirpated specimen showed
      clear cell carcinoma which was suspected to be a metastasis from renal cell
      carcinoma. Subsequent urologic examination disclosed the right renal tumor. Since
      there were no other systemic metastases, right nephrectomy was performed.
      Pathologically, the renal tumor was clear cell subtype renal cell carcinoma and
      had the same histology as the frontal sinus tumor.

PMID- 9546128
TI  - [A case of renal cell carcinoma in a nonfunctioning kidney caused by staghorn
      calculus].
AB  - A 62-year-old man was referred to our clinic with a chief complaint of gross
      hematuria. He had bilateral renal staghorn calculi at the age of 50 years and had
      undergone left nephrolithotomy. However, no treatment had been given to the right
      staghorn calculi associated with nonfunctioning kidney. Imaging diagnosis
      demonstrated no mass lesions in the bilateral kidneys. Right nephrectomy revealed
      renal cell carcinoma, tubular type, mixed subtype, G2, INF-beta with lymph node
      metastasis to the renal hilum. Cancer cells infiltrated diffusely throughout the
      entire renal parenchyma. He died of progressive metastases 15 months
      postoperatively.

PMID- 9546129
TI  - [Clinical application of intraoperative ultrasonography for bilateral
      multilocular cystic renal cell carcinoma: a case report].
AB  - A 45-year-old man was referred to our department for further examination of the
      renal complicated cyst which was found incidentally by ultrasonography. Another
      complicated cyst in the left kidney was detected by subsequent dynamic CT and
      ultrasonography, which suggested bilateral cystic renal cell carcinoma. Bilateral
      partial nephrectomy was performed. Intraoperative ultrasonography was useful for
      diagnosis of multilocular cystic renal cell carcinoma (MCRCC). It disclosed
      multiple septa of the right renal complicated cyst which were not revealed by any
      preoperative examinations. It was also a useful adjunct to partial nephrectomy.
      It helped to identify the extent of deep intra-parenchymal lesions. The final
      diagnosis was bilateral synchronous multilocular cystic renal cell carcinoma.
      This is the second case of bilateral synchronous multilocular cystic renal cell
      carcinoma reported in Japan. We reviewed the clinical characteristics of 59 cases
      of MCRCC in the Japanese literature including the present case.

PMID- 9546130
TI  - [Kidney-sparing surgery for recurrent ureteral and bladder cancers in an aged
      patient with functionally solitary horseshoe kidney].
AB  - A 79-year-old woman was admitted with recurrent ureteral and bladder cancers. She
      had a horseshoe kidney with a non-functioning right renal unit. Fifteen months
      earlier, multiple urothelial tumors had first developed in the left upper ureter
      and bladder. Transurethral resection of bladder tumor (TUR-Bt) and partial
      ureterectomy (2 cm) had been performed. Presently, the recurrent tumors were
      located at the left lower ureter and bladder. Considering the high age of the
      patient, TUR-Bt and partial ureterectomy (5 cm) were performed. Besides
      urothelial cancers, she had been operated for carcinomas of the colon, uterus and
      stomach. Kidney-sparing therapy has successfully maintained her quality of life.

PMID- 9546131
TI  - [Retrovesical liposarcoma: a case report].
AB  - A case of retrovesical liposarcoma is reported. The patient was a 41-year-old man
      who complained of left scrotal pain and of hip discomfort. Digital rectal
      examination revealed a hen's egg-sized mass with an elastic hard consistency at
      the left side of the normal prostate. Pelvic CT and MRI showed a heterogeneous
      tumor in the retrovesical region. Transperineal biopsy revealed liposarcoma.
      Pelvic exenteration, colostomy and ileal conduit were performed. The resected
      weight was 1,680 grams, and the histopathological diagnosis was myxoid type of
      liposarcoma, grade II. Postoperatively, a metastatic lesion to vertebrae
      thoracicae I developed causing radiculoneuropathy of the left superior limb. Spot
      radiation (50 Gy) was administered to the lesion, but there was no response.
      Currently, the patient is being treated with combination chemotherapy consisting
      of dacarbazine, vincristine, adriamycin, and cyclophosphamide. Cases of
      retrovesical liposarcomas reported in Japan are reviewed and discussed.

PMID- 9546132
TI  - [A case of multiple organ failure with massive intestinal bleeding caused by
      methicillin-resistant Staphylococcus aureus in a postcystectomy patient--efficacy
      of mask continuous positive airway pressure training and intraarterial
      embolization].
AB  - A 51-year-old man underwent radical cystectomy with tubeless cutaneous
      ureterostomy. Methicillin-resistant Staphylococcus aureus (MRSA) enteritis
      developed postoperatively. MRSA caused critical infections such as pneumonia and
      sepsis, which subsequently progressed to adult respiratory distress syndrome,
      massive melena and multiple organ failure. The patient was rescued by intensive
      management including mask continuous positive airway pressure, systemic
      vancomycin administration and intraarterial embolization to stop jejunal
      bleeding.

PMID- 9546133
TI  - [A case of poorly differentiated adenocarcinoma of prostate with neuroendocrine
      differentiation].
AB  - A 59-year-old man was diagnosed with clinical stage D1 poorly differentiated
      prostatic adenocarcinoma (PAC). The patient was treated with total androgen
      blockade therapy. The tumor recurred 18 months later. Digital rectal examination
      revealed a large, stony-hard prostate. The serum PSA level was within normal
      limits. Pathological examination of the prostate revealed conventional
      adenocarcinoma with large numbers of neuroendocrine (NE) cells. The patient died
      3 months after the diagnosis of PAC with NE differentiation, 22 months after the
      initial diagnosis of prostate cancer.

PMID- 9546134
TI  - [A case of prostatic tuberculosis: usefulness of transrectal ultrasound in
      diagnosis].
AB  - A case of prostatic tuberculosis is reported. A 61-year-old male visited our
      clinic complaining of urinary retention. On digital rectal examination, the
      prostate was found to be enlarged, hard, and uneven. Transrectal ultrasound
      revealed a large hypoechoic lesion in the posterior aspect of the prostate.
      Transrectal ultrasound guided systematic biopsies of the prostate were performed.
      The specimens obtained from the hypoechoic lesion, were diagnosed
      histopathologically as prostatitis with epithelioid granuloma, Langhans' type
      giant cells, and caseous necrosis. Mycobacterium tuberculosis was detected in the
      physiological saline solution injected into the urethra after prostatic massage.
      The patient was diagnosed as having prostatic tuberculosis and underwent
      antituberculotic therapy with INH and RFP. Transrectal ultrasound seemed to be
      useful in detecting histopathological changes associated with tuberculosis in the
      prostate.

PMID- 9546135
TI  - Leiomyoma of the spermatic cord extending along the vas deferens.
AB  - We report an unusual case of a leiomyoma of the spermatic cord. The tumor did not
      present as a mass but presented as a hard structure along the spermatic cord. To
      our knowledge, this is the first case report of a leiomyoma of the spermatic cord
      with such an unusual appearance.

PMID- 9546136
TI  - [Chronic perianal pyoderma with urethrocutaneous fistula: a case report].
AB  - A 65-year-old male was hospitalized because of micturition pain and urinary
      oozing from several fistulas on the perineal and the left gluteal skin. Oozing
      had been present for about 50 years, after receiving mass resection of his left
      scrotum or perineum, and left orchiectomy. The main focus was on the left dorsal
      site of the anus. Compression around this area produced malodorous grayish pus
      discharge from many fistulas, although the anus was intact. Although he had
      histories of spinal caries and renal tuberculosis, both pus and urine cultures
      showed Staphylococcus spp. and no growth of Mycobacterium tuberculosis.
      Urethrocystography showed urethral stenosis at bulbar urethra and leakage from a
      site just proximal to the stenosis. Antibiotics for tuberculosis were
      administrated for fear of recurrent tuberculosis for 6 months. Cystostomy
      formation and debridement were performed, followed by en-bloc resection and mesh
      skin graft after two weeks. Internal urethrotomy was performed six months after
      the surgery, and subsequently cystostomy removed. After three and a half years,
      although there was no local recurrence and no difficulty of urination, he died of
      cholangio-carcinoma. There are many reports of chronic perianal pyoderma
      subsequent to hemorrhoid or subcutaneous abscess; however, this might be the
      first report on a case originating from fistulas in the urinary tract.

PMID- 9546138
TI  - [Informed consent in the terminal care].
AB  - One of the biggest problems to perform terminal care is how to communicate with
      patient's families. Mental stresses of patients who are expected to die and of
      their families are extremely serious. To release their stresses, kind and
      detailed explanation of patient condition should be given every day by the
      clinical team consisted of doctors and nurses. We should realize that mental
      support given by the clinical staff would be an important care point to alleviate
      the stresses of patients and to alleviate the stresses and the strains of their
      families. And we can say that performing terminal care is essential to promote
      informed consent.

PMID- 9546137
TI  - [A case of labial adhesions in an elderly woman].
AB  - A 90-year-old woman was admitted with a chief complaint of difficulty in
      urination. She had severe labial adhesions with a pin point opening. Urinary
      tract infection was detected by urine examination. The adhesions were surgically
      dissected under local anesthesia and recurrence was not seen at follow-up 6
      months after the operation. Labial adhesions in adult women are rare and only 28
      cases of labial adhesions in adults have been reported in the Japanese
      literature. Labial adhesions in adults may be more closely related with chronic
      inflammation such as recurrent urinary tract infections and vulvovaginitis than
      in pediatric cases.

PMID- 9546139
TI  - [Surgery for cancer patients and informed consent].
AB  - Cancer treatment in medical centers traditionally provide high-quality medical
      care but are often perceived by patients to be lacking in humanity, respect for
      individual dignity, and personal comfort. The most important features of approach
      are that patients are more informed about their condition and medical options
      than before, and another point is growing recognition of the importance of caring
      not only for the body but also for the personal, emotional, educational needs of
      cancer patients and their families.

PMID- 9546140
TI  - [The importance of informed consent in the field of ophthalmology].
AB  - Ocular diseases have some characteristics that are different from diseases of
      other organs. First, patients clearly can judge for themselves whether or not
      they can see better postoperatively. Second, because several parameters such as
      visual acuity and intraocular pressure, are obtained from patients, patient's
      families and others can objectively judge the post-treatment status. Therefore,
      clinical information is easily available to others besides the physician. Third,
      except for acute ocular diseases such as retinal detachment, acute glaucoma, and
      ocular trauma that easily can result in blindness, ophthalmologists usually treat
      eyes that will maintain a certain visual acuity level. These are the primary
      reasons why patients and families complain about unfavorable post-treatment
      subjective symptoms. Because of these three characteristics of ocular disease,
      informed consent (IC) is extremely important in the field of ophthalmology. I
      studied ophthalmology and IC at Harvard Medical School, Boston, from 1980 to
      1983, and again in 1989. Strict IC is mandatory in the United States. However,
      the concept of IC in the US cannot always be adapted to fit Japanese culture. The
      different legal concepts of IC in the two countries are discussed in this paper.
      Since I returned to Japan, our Department of Ophthalmology incorporated several
      new concepts into our clinical practice. For example, we now broadcast live
      surgeries of patients with severe proliferative diabetic retinopathy by closed
      circuit TV to their families in the hospital. This has fostered great
      communication and confidence among patients, their families, and doctors. In
      1994, we also began inter-hospital and international IC via telemedicine and
      telescience. The video conferencing system VisionSeries (Panasonic Broadcast and
      Television System Company) is used to communicate between Asahikawa Medical
      University and 10 branch hospitals. INS net 1500 or INS net 64 (3 lines)
      transmits full-motion (30 frames/second) color fundus images and biomicroscopic
      images. Ocular surgeries performed by ophthalmologists using operating
      microscopes at each branch hospital also are transmitted to Asahikawa Medical
      University to facilitate consultation with more experienced ophthalmologists. The
      transmitted images of the fundus and biomicroscopic findings are satisfactory,
      and they allow surgeons to conduct useful discussions among themselves and with
      the family members during the surgeries in real time. When the patients' families
      are in local cities, surgeons can transmit the operations via the telemedicine
      system link to the nearby hospital, and the ophthalmologists there can narrate
      the surgeries in real time. On November 14, 1996, our technology was used
      internationally for the first time to transmit ocular images and live ocular
      surgeries between Asahikawa Medical University, Japan, and the Schepens Eye
      Research Institute, Harvard Medical School, Boston, MA, USA. Telemedicine and
      telesurgery will be useful scientific tools in the field of Ophthalmology in the
      near future. We believe that this technology literally opens up the world to
      scientific and medical collaboration. Patients with vision deficiencies and
      blinding disease are certain to be the ultimate beneficiaries of these
      interactions. Lastly, ideal implementation of IC in the field of Ophthalmology
      are discussed in this paper.

PMID- 9546141
TI  - [Role of nursing informed consent].
AB  - Informed consent is important for medical practice. Pilot study of comprehensive
      discharge planning at Higashi Sapporo Hospital suggested that there was a
      relationship between informed consent and patients' length of stay. Also in a
      study of home care systems for advanced cancer patients, it was one of the most
      important factors that they knew their true diagnoses, especially in young cancer
      patients. Informed consent, that is shared decision making, is an important
      communication process between patients and professional care givers. We consider
      the roles of nursing for informed consent are as follows: 1. Support of patients'
      decision making; 1) promotion of patients' understanding of their own situation,
      a. active listening, b. information disclosure, c. psychological support, 2)
      advocation, 3) assisting patients understanding of doctor's explanations, 2.
      Promotion of good relationships between patients and professional staff, 3.
      Coordination with patients and/or their families and/or professional care givers,
      4. Ethical issues, and 5. Education for health promotion. However there are some
      problems remaining: for example, 1. Nurses after feel then have little role in
      informed consent, which is an issue for physicians. 2. Nurses must improve their
      professional skill and knowledge, 3. Nurses must perform more actively and
      independently.

PMID- 9546142
TI  - [The medical health care of the elderly and the informed consent].

PMID- 9546143
TI  - [Informed consent in psychosomatic medicine].
AB  - Obtaining informed consent perfectly is very difficult from the view of
      psychosomatic medicine. Medical education regarding informed consent is generally
      of a low level. However as it is important to defend patients' human rights, we
      must educate them as to the precise meaning of both "informed" and "consent". In
      this report I have tried to demonstrate that both the education of medical
      students and their social consciousness are very important. I examined students'
      opinions regarding the care of a sudden case of hysterectomy (Porro's emergent
      operation). The following students were involved: 1st year medical students (N =
      73), 4th year (N = 85) and 6th year (N = 119), and 3rd year nursing students (N =
      42) and midwife students (N = 27). I examined their answers by transactional
      analysis. The answers of the 1st year medical students reflecting the view of the
      child ego state were significantly greater than those of the other students (P <
      0.01). But following my lecture the answers of the same 1st year students altered
      to reflect the view of the adult ego more (P < 0.05). We opened "the key center
      of psychosomatic women's health in Japan" in our clinic two years ago. Since then
      we have talked every month to people in general about various women's diseases,
      and also discussed various problems of the doctor-patient relationships during
      these talks. I feel that public awareness concerning informed consent has
      increased gradually recently in Japan.

PMID- 9546144
TI  - [Informed consent--on the right of self-determination].
AB  - The idea of informed consent asks for the right of self-determination which is
      very difficult to achieve. Human life does not depend on one's will, and neither
      does suffering. That is human being does not control one's own life, even though
      one must be responsible for it. The right of self-determination has long and
      struggling history. As a result we have acquired the concept of informed consent.
      And then the physician-patient relationship is no longer considered to be based
      on paternalism and now the new model is seeked for. All human beings are mortal
      and cannot inevitably escape suffering. Therefore we must consider the physician
      patient relationship as the one based on equality. The problem of self
      determination should arise from this understanding.

PMID- 9546145
TI  - [Experimental study on the therapeutic effects of SMS201-995 on bile-induced
      acute pancreatitis in the dog].
AB  - We studied the effects of SMS201-995, a long-acting somatostatin analogue, on
      bile-induced acute pancreatitis in the dog. According to morphometrical study,
      parenchymal necrotic ratio, zymogen granules area and zymogen granules occupied
      ratio of acinus were significantly decreased in SMS-treated pancreatitis. These
      results suggests that SMS-treated pancreatitis showed less damage than non
      treated ones and decreased secretion of pancreatic enzyme. On the other hand,
      pancreatic blood flow showed a stronger decrease in SMS-treated dogs than in non
      treated ones, and a significant difference was observed at 15 minutes and 1 hour
      after induction of pancreatitis. Many clinical and experimental evidences suggest
      that pancreatic ischemia causes acute pancreatitis. Pancreatitis may be worsened
      by an early phase treatment with SMS201-995, because this substance reduces
      pancreatic tissue blood flow. The harmful effect of this substance on pancreatic
      tissue blood flow must be kept in mind when SMS201-995 is used for therapeutic
      purpose of acute pancreatitis.

PMID- 9546146
TI  - Emergency appendectomy in a patient with Eisenmenger's syndrome.
AB  - For the successful management of an emergency appendectomy and abscess drainage
      in an Eisenmenger's patient with diffuse peritonitis, it may be preferable to use
      general anesthesia with awake intubation. Epidural anesthesia is commonly
      combined with this anesthetic management for emergency abdominal surgery.
      However, the combination of topical anesthesia with epidural anesthesia should be
      avoided for fear of toxicity of local anesthetics in a patient with complications
      due to Eisenmenger's syndrome.

PMID- 9546147
TI  - [Morphological studies on lower margins of nasal aperture in the skull of
      Hokkaido Japanese].
AB  - It is well-known that the lower margins of nasal aperture in the human skull may
      be classified into the following four types, i.e., Forma anthropina, Forma
      infantilis, Fossae praenasales and Clivus nasoalveolaris, and that the rates of
      appearance of these four types differ with races. In the present study we made
      morphological studies on the lower margins of nasal aperture of 465 Hokkaido
      Japanese skulls, 463 skulls with symmetrical nasal aperture and 2 skulls with
      asymmetrical one, and compared the findings with those of all races in the world,
      especially of the Japanese, Ainu, Moyoro Man, Hamanaka Site Man and Eskimo. Forma
      anthropina was found in 330 skulls (71.27 +/- 2.10%) among the 463, marking the
      highest rate. Forma infantilis, found in 74 skulls (15.98 +/- 1.70%) among the
      463, marked the second highest rate. Fossae praenasales, found in 42 skulls (9.07
      +/- 1.33%) among the 463, marked the third highest rate. These 42 cases of Fossae
      praenasales were further classified into three types, i.e., sub-Forma infantilis,
      17 (40.48%), typical Fossae prenasales, 23 (54.76%) and sub-Clivus
      nasoalveolaris, 2 (4.76%). Clivus nasoalveolaris, found in 17 skulls (3.67 +/-
      0.87%) among the 463, marked the lowest rate. As a whole, the rates of the four
      types in the Hokkaido Japanese were close to those in the other groups of the
      Japanese in Kinai and Hokkaido (Ito).

PMID- 9546148
TI  - [Effects of physical exhaustion on immune systems].
AB  - The present study was performed to elucidate the effects of physical fatigue on
      immune parameters of peripheral blood and splenic T cells in rats. Male Wistar
      rats aged 20 to 45 weeks were used for the experiment. Swimming was employed as a
      physical fatigue load. The rats in the single-load group with a weight equal to
      3% of the body weight of each rat connected to the tails were exhausted by two
      hours of swimming in one day. The rats in the consecutive-load group were
      exhausted by three hours of swimming for 7 consecutive days with a weight equal
      to 5% of the body weight of each rat. Absolute numbers of total white blood cells
      (WBCs) and peripheral blood lymphocytes decreased significantly just after
      swimming and returned to the baseline one day after swimming in both the single-
      and consecutive-load groups. However, in the consecutive-load group WBCs and
      lymphocytes decreased 7 days after swimming. Concentrations of plasma
      corticosterone increased significantly just after swimming, and returned to the
      baseline one day after swimming in both groups. Percentages of peripheral blood
      CD5+ cells, CD4+ cells and CD8+ cells in the single-load group increased
      significantly just after swimming. The percentage of peripheral blood CD5+ cells
      and CD4+ cells increased significantly one day after swimming in the consecutive
      load group. Percentages of splenic CD5+ cells and CD4+ cells increased
      significantly in the single-load group. However, only that of CD4+ cells
      increased significantly just after swimming in the consecutive-load group. A
      single load affected the proportions of CD5+ cells, CD4+ cells and CD8+ cells
      just after the load but the consecutive load affected CD5+ cells and CD4+ cells
      and the effect persisted until the next day. These results indicate that the
      effect of fatigue on immune parameters depends on the level of fatigue, and that
      measurement of subsets of peripheral blood T cells is useful for evaluating
      various levels of fatigue.

PMID- 9546149
TI  - [Morphometrical analysis of projection neurons in reeler mutant mice].
AB  - The projection neurons in the cerebral cortex are localized in the specific
      layers, and present the characteristic shape of cell bodies and dendritic
      arborization according to their properties. To examine what factors could cause
      the morphological characteristics of the reeler neurons, of which cortical layers
      are generally inverted, we morphometrically analyzed three types of projection
      neurons, callosal (CC-neurons), corticospinal (CS-neurons), and corticothalamic
      neurons (CT-neurons), by the retrograded labeling method. The results were as
      follows: 1) Although in the normal mice, the CC-neuron cell bodies in the layer 2
      + 3 were significantly smaller than ones in the layer 5, the reeler CC-neurons
      were uniform regardless of their intracortical positions. 2) The cell bodies of
      the reeler CS-neurons were normal in size throughout the entire cortex. 3) The
      cell bodies of reeler CT-neurons were generally larger than normal ones, and they
      were larger in the location near the pia mater. 4) The apical dendrites of the
      normal CC-, CS- and CT-neurons were generally directed toward the layer 1 of
      neocortex, which is the plexiform zone (PZ) in the embryo stage, whereas those of
      the reeler CC- and CS-neurons were directed toward the upper-middle zone of
      neocortex, which is the interplexiform zone (IPZ) that corresponds with the
      normal PZ; however, those of the reeler CT-neurons were not oriented toward
      dominant direction. These results suggest that the sizes of CS-neurons vary
      depending upon the target of the projection, whereas CC- and CT-neurons are
      influenced by the volume of afferent inputs as well as the target of the
      projection. The afferent factors, especially thalamocortical fibers, may also
      influence the direction of the apical dendrites of CT-neurons.

PMID- 9546151
TI  - Alkane hydroxylase from Acinetobacter sp. strain ADP1 is encoded by alkM and
      belongs to a new family of bacterial integral-membrane hydrocarbon hydroxylases.
AB  - Degradation of long-chain alkanes by Acinetobacter sp. strain ADP1 involves
      rubredoxin and rubredoxin reductase. We complemented a mutant deficient in alkane
      utilization and sequenced four open reading frames (ORFs) on the complementing
      DNA. Each of these ORFs was disrupted by insertional mutagenesis on the
      chromosome. As determined from sequence comparisons, ORF1 and ORF4 seem to encode
      a rotamase of the PpiC type and an acyl coenzyme A dehydrogenase, respectively.
      Disruption of these ORFs does not affect alkane utilization. In contrast, the two
      other ORFs, alkR and alkM, are essential for growth on alkanes as sole carbon
      sources. alkR encodes a polypeptide with extensive homology to AraC-XyIS-like
      transcriptional regulators. It is located next to alkM, which encodes the
      terminal alkane hydroxylase, but is in the opposite orientation. Sequence
      homologies with other bacterial integral-membrane hydrocarbon hydroxylases
      suggest that AlkM may be the first member of a new protein family. The genes
      identified here are not linked to the rubredoxin- and rubredoxin reductase
      encoding genes on the Acinetobacter sp. strain ADP1 chromosome.

PMID- 9546150
TI  - Differential transmission of the genospecies of Borrelia burgdorferi sensu lato
      by game birds and small rodents in England.
AB  - The genetic diversity of Borrelia burgdorferi sensu lato was assessed in a focus
      of Lyme borreliosis in southern Britain dominated by game birds. Ticks, rodents,
      and pheasants were analyzed for spirochete infections by PCR-targeting the 23S-5S
      rRNA genes, followed by genotyping by the reverse line blot method. In questing
      Ixodes ricinus ticks, three genospecies of B. burgdorferi sensu lato were
      detected, with the highest prevalences found for Borrelia garinii and Borrelia
      valaisiana. B. burgdorferi sensu stricto was rare (< 1%) in all tick stages.
      Borrelia afzelia was not detected in any of the samples. More than 50% of
      engorged nymphs collected from pheasants were infected with borreliae, mainly B.
      garinii and/or B. valaisiana. Although 19% of the rodents harbored B. burgdorferi
      sensu stricto and/or B. garinii in internal organs, only B. burgdorferi sensu
      stricto was transmitted to xenodiagnostic tick larvae (it was transmitted to 1%
      of the larvae). The data indicate that different genospecies of B. burgdorferi
      sensu lato can be maintained in nature by distinct transmission cycles involving
      the same vector tick species but different vertebrate host species. Wildlife
      management may have an influence on the relative risk of different clinical forms
      of Lyme borreliosis.

PMID- 9546153
TI  - Effects of bacterial host and dichloromethane dehalogenase on the competitiveness
      of methylotrophic bacteria growing with dichloromethane.
AB  - Methylobacterium sp. strain DM4 and Methylophilus sp. strain DM11 can grow with
      dichloromethane (DCM) as the sole source of carbon and energy by virtue of
      homologous glutathione-dependent DCM dehalogenases with markedly different
      kinetic properties (the kcat values of the enzymes of these strains are 0.6 and
      3.3 S-1, respectively, and the Km values are 9 and 59 microM, respectively).
      These strains, as well as transconjugant bacteria expressing the DCM dehalogenase
      gene (dcmA) from DM11 or DM4 on a broad-host-range plasmid in the background of
      dcmA mutant DM4-2cr, were investigated by growing them under growth-limiting
      conditions and in the presence of an excess of DCM. The maximal growth rates and
      maximal levels of dehalogenase for chemostat-adapted bacteria were higher than
      the maximal growth rates and maximal levels of dehalogenase for batch-grown
      bacteria. The substrate saturation constant of strain DM4 was much lower than the
      Km of its associated dehalogenase, suggesting that this strain is adapted to
      scavenge low concentrations of DCM. Strains and transconjugants expressing the
      DCM dehalogenase from strain DM11, on the other hand, had higher growth rates
      than bacteria expressing the homologous dehalogenase from strain DM4. Competition
      experiments performed with pairs of DCM-degrading strains revealed that a strain
      expressing the dehalogenase from DM4 had a selective advantage in continuous
      culture under substrate-limiting conditions, while strains expressing the DM11
      dehalogenase were superior in batch culture when there was an excess of
      substrate. Only DCM-degrading bacteria with a dcmA gene similar to that from
      strain DM4, however, were obtained in batch enrichment cultures prepared with
      activated sludge from sewage treatment plants.

PMID- 9546155
TI  - Self-transmissible mercury resistance plasmids with gene-mobilizing capacity in
      soil bacterial populations: influence of wheat roots and mercury addition.
AB  - A set of mercury resistance plasmids was obtained from wheat rhizosphere soil
      amended or not amended with mercuric chloride via exogenous plasmid isolation by
      using Pseudomonas fluorescens R2f, Pseudomonas putida UWC1, and Enterobacter
      cloacae BE1 as recipient strains. The isolation frequencies were highest from
      soil amended with high levels of mercury, and the isolation frequencies from
      unamended soil were low. With P. putida UWC1 as the recipient, the isolation
      frequency was significantly enhanced in wheat rhizosphere compared to bulk soil.
      Twenty transconjugants were analyzed per recipient strain. All of the
      transconjugants contained plasmids which were between 40 and 50 kb long. Eight
      selected plasmids were distributed among five groups, as shown by restriction
      digestion coupled with a similarity matrix analysis. However, all of the plasmids
      formed a tight group, as judged by hybridization with two whole-plasmid probes
      and comparisons with other plasmids in dot blot hybridization analyses. The
      results of replicon typing and broad-host-range incompatibility (Inc) group
      specific PCR suggested tht the plasmid isolates were not related to any
      previously described Inc group. Although resistance to copper, resistance to
      streptomycin, and/or resistance to chloramphenicol was found in several plasmids,
      catabolic sequences were generally not identified. One plasmid, pEC10,
      transferred into a variety of bacteria belonging to the beta and gamma
      subdivisions of the class Proteobacteria and mobilized as well as retromobilized
      the IncQ plasmid pSUP104. A PCR method for detection of pEC10-like replicons was
      used, in conjunction with other methods, to monitor pEC10-homologous sequences in
      mercury-polluted and unpolluted soils. The presence of mercury enhanced the
      prevalence of pEC10-like replicons in soil and rhizosphere bacterial populations.

PMID- 9546154
TI  - Population dynamics of phenol-degrading bacteria in activated sludge determined
      by gyrB-targeted quantitative PCR.
AB  - A method for quantifying bacterial populations introduced into an activated
      sludge microbial community is described. The method involves extraction of DNA
      from activated sludge, appropriate dilution of the extracted DNA with DNA
      extracted from nonintroduced activated sludge, PCR amplification of a gyrB gene
      fragment from the introduced strain with a set of strain-specific primers, and
      quantification of the electrophoresed PCR product by densitometry. The adequacy
      of the method was examined by analyzing the population dynamics of two phenol
      degrading bacteria, Pseudomonas putida BH and Comamonas sp. strain E6, that had
      been introduced into phenol-digesting activated sludge. The density of each of
      the two populations determined by the PCR method immediately after the
      introduction was consistent with the density estimated from a plate count of the
      inoculum. This quantitative PCR method revealed different population dynamics for
      the two strains in the activated sludge under different phenol-loading
      conditions. The behavior of both of these strains in the activated sludge
      reflected the growth kinetics of the strains determined in laboratory axenic
      cultures.

PMID- 9546156
TI  - Production of the carotenoids lycopene, beta-carotene, and astaxanthin in the
      food yeast Candida utilis.
AB  - The food-grade yeast Candida utilis has been engineered to confer a novel
      biosynthetic pathway for the production of carotenoids such as lycopene, beta
      carotene, and astaxanthin. The exogenous carotenoid biosynthesis genes were
      derived from the epiphytic bacterium Erwinia uredovora and the marine bacterium
      Agrobacterium aurantiacum. The carotenoid biosynthesis genes were individually
      modified based on the codon usage of the C. utilis glyceraldehyde 3-phosphate
      dehydrogenase gene and expressed in C. utilis under the control of the
      constitutive promotes and terminators derived from C. utilis. The resultant yeast
      strains accumulated lycopene, beta-carotene, and astaxanthin in the cells at 1.1,
      0.4, and 0.4 mg per g (dry weight) of cells, respectively. This was considered to
      be a result of the carbon flow into ergosterol biosynthesis being partially
      redirected to the nonendogenous pathway for carotenoid production.

PMID- 9546157
TI  - Specificity of milk peptide utilization by Lactococcus lactis.
AB  - To study the substrate specificity of the oligopeptide transport system of
      Lactococcus lactis for its natural substrates, the growth of L. lactis MG1363 was
      studied in a chemically defined medium containing milk peptides or a tryptic
      digest of alpha s2-casein as the source of amino acids. Peptides were separated
      into acidic, neutral, and basic pools by solid-phase extraction or by cation
      exchange liquid chromatogrpaphy. Their ability to sustain growth and the time
      course of their utilization demonstrated the preferential use of hydrophobic
      basic peptides with molecular masses ranging between 600 and 1,100 Da by L.
      lactis MG1363 and the inability to use large, acidic peptides. These peptide
      utilization preferences reflect the substrate specificity of the oligopeptide
      transport system of the strain, since no significant cell lysis was inferred.
      Considering the free amino acid content of milk and these findings on peptide
      utilization, it was demonstrated that the cessation of growth of L. lactis MG1363
      in milk was due to deprivation of leucine and methionine.

PMID- 9546158
TI  - PCR for detection of Shigella spp. in mayonnaise.
AB  - The use of PCR to amplify a specific virA gene fragment serves as a highly
      specific and sensitive method to detect virulent bacteria of the genus Shigella
      and enteroinvasive Escherichia coli. Amplification of a 215-bp DNA band was
      obtained by using isolated genomic DNA of Shigella, individual cells of Shigella
      dysenteriae, and mayonnaise contaminated with S. dysenteriae. Moreover, a
      multiplex PCR with specific (virA) and bacterium-restricted (16S ribosomal DNA)
      primers generated an amplification product of approximately 755 bp for all
      bacteria tested and an additional 215-bp product for Shigella and enteroinvasive
      E. coli.

PMID- 9546160
TI  - 19F nuclear magnetic resonance as a tool to investigate microbial degradation of
      fluorophenols to fluorocatechols and fluoromuconates.
AB  - A method was developed to study the biodegradation and oxidative
      biodehalogenation of fluorinated phenols by 19F nuclear magnetic resonance (NMR).
      Characterization of the 19F NMR spectra of metabolite profiles of a series of
      fluorophenols, converted by purified phenol hydroxylase, catechol 1,2
      dioxygenase, and/or by the yeast-like fungus Exophiala jeanselmei, provided
      possibilities for identification of the 19F NMR chemical shift values of
      fluorinated catechol and muconate metabolites. As an example, the 19F NMR method
      thus defined was used to characterize the time-dependent metabolite profiles of
      various halophenols in either cell extracts or in incubations with whole cells of
      E. jeanselmei. The results obtained for these two systems are similar, except for
      the level of muconates observed. Altogether, the results of the present study
      describe a 19F NMR method which provides an efficient tool for elucidating the
      metabolic pathways for conversion of fluorine-containing phenols by
      microorganisms, with special emphasis on possibilities for biodehalogenation and
      detection of the type of fluorocatechols and fluoromuconates involved. In
      addition, the method provides possibilities for studying metabolic pathways in
      vivo in whole cells.

PMID- 9546161
TI  - Grazing of Tetrahymena sp. on adhered bacteria in percolated columns monitored by
      in situ hybridization with fluorescent oligonucleotide probes.
AB  - Predation of attached Pseudomonas putida mt2 by the small ciliate Tetrahymena sp.
      was investigated with a percolated column system. Grazing rates were examined
      under static and dynamic conditions and were compared to grazing rates in batch
      systems containing suspended prey. The prey densities were 2 x 10(8) bacteria per
      ml of pore space and 2 x 10(8) bacteria per ml of suspension, respectively.
      Postingestion in situ hybridization of bacteria with fluorescent oligonucleotide
      probes was used to quantify ingestion. During 30 min, a grazing rate of 1,382 +/-
      1,029 bacteria individual-1 h-1 was obtained with suspended prey; this was twice
      the grazing rate observed with attached bacteria under static conditions.
      Continuous percolation at a flow rate of 73 cm h-1 further decreased the grazing
      rate to about 25% of the grazing rate observed with suspended prey. A
      considerable proportion of the protozoans fed on neither suspended bacteria nor
      attached bacteria. The transport of ciliates through the columns was monitored at
      the same time that predation was monitored. Less than 20% of the protozoans
      passed through the columns without being retained. Most of these organisms
      ingested no bacteria, whereas the retained protozoans grazed more efficiently.
      Retardation of ciliate transport was greater in columns containing attached
      bacteria than in bacterium-free columns. We propose that the correlation between
      grazing activity and retardation of transport is a consequence of the interaction
      between active predators and attached bacteria.

PMID- 9546162
TI  - Characterization of the rrnB operon of the plant pathogen Rhodococcus fascians
      and targeted integrations of exogenous genes at rrn loci.
AB  - A 6.0-kb SalI DNA fragment containing an entire rRNA operon (rrnB) was cloned
      from a cosmid gene bank of the phytopathogenic strain Rhodococcus fascians D188.
      The nucleotide sequence of the 6-kb fragment was determined and had the
      organization 16S rRNA-spacer-23S rRNA-spacer-5S rRNA without tRNA-encoding genes
      in the spacer regions. The 5' and 3' ends of the mature 16S, 23S, and 5S rRNAs
      were determined by alignment with the rrn operons of Bacillus subtilis and other
      gram-positive bacteria. Four copies of the rrn operons were identified by
      hybridization with an rrnB probe in R. fascians type strain ATCC 12974 and in the
      virulent strain R. fascians D188. However, another isolate, CECT 3001 (= NRRL
      B15096), also classified as R. fascians, produced five rrn-hybridizing bands. An
      integrative vector containing a 2.5-kb DNA fragment internal to rrnB was
      constructed for targeted integration of exogenous genes at the rrn loci.
      Transformants carrying the exogenous chloramphenicol resistance gene (cmr)
      integrated in different rrn operons were obtained. These transformants had normal
      growth rates in complex medium and minimal medium and were fully stable for the
      integrated marker.

PMID- 9546163
TI  - Characterization of the dominant and rare members of a young Hawaiian soil
      bacterial community with small-subunit ribosomal DNA amplified from DNA
      fractionated on the basis of its guanine and cytosine composition.
AB  - The small-subunit ribosomal DNA (rDNA) diversity was found to be very high in a
      Hawaiian soil community that might be expected to have lower diversity than the
      communities in continental soils because the Hawaiian soil is geographically
      isolated and only 200 years old, is subjected to a constant climate, and harbors
      low plant diversity. Since an underlying community structure could not be
      revealed by analyzing the total eubacterial rDNA, we first fractionated the DNA
      on the basis of guanine-plus-cytosine (G + C) content by using bisbenzimidazole
      and equilibrium centrifugation and then analyzed the bacterial rDNA amplified
      from a fraction with a high biomass (63% G + C fraction) and a fraction with a
      low biomass (35% G + C fraction). The rDNA clone libraries were screened by
      amplified rDNA restriction analysis to determine phylotype distribution. The
      dominant biomass reflected by the 63% G + C fraction contained several dominant
      phylotypes, while the community members that were less successful (35% G + C
      fraction) did not show dominance but there was a very high diversity of
      phylotypes. Nucleotide sequence analysis revealed taxa belonging to the groups
      expected for the G + C contents used. The dominant phylotypes in the 63% G + C
      fraction were members of the Pseudomonas, Rhizobium-Agrobacterium, and
      Rhodospirillum assemblages, while all of the clones sequenced from the 35% G + C
      fraction were affiliated with several Clostridium assemblages. The two-step rDNA
      analysis used here uncovered more diversity than can be detected by direct rDNA
      analysis of total community DNA. The G + C separation step is also a way to
      detect some of the less dominant organisms in a community.

PMID- 9546164
TI  - Pyruvate decarboxylase catalyzes decarboxylation of branched-chain 2-oxo acids
      but is not essential for fusel alcohol production by Saccharomyces cerevisiae.
AB  - The fusel alcohols 3-methyl-1-butanol, 2-methyl-1-butanol, and 2-methyl-propanol
      are important flavor compounds in yeast-derived food products and beverages. The
      formation of these compounds from branched-chain amino acids is generally assumed
      to occur via the Ehrlich pathway, which involves the concerted action of a
      branched-chain transaminase, a decarboxylase, and an alcohol dehydrogenase.
      Partially purified preparations of pyruvate decarboxylase (EC 4.1.1.1) have been
      reported to catalyze the decarboxylation of the branched-chain 2-oxo acids formed
      upon transamination of leucine, isoleucine, and valine. Indeed, in a coupled
      enzymatic assay with horse liver alcohol dehydrogenase, cell extracts of a wild
      type Saccharomyces cerevisiae strain exhibited significant decarboxylation rates
      with these branched-chain 2-oxo acids. Decarboxylation of branched-chain 2-oxo
      acids was not detectable in cell extracts of an isogenic strain in which all
      three PDC genes had been disrupted. Experiments with cell extracts from S.
      cerevisiae mutants expressing a single PDC gene demonstrated that both PDC1- and
      PDC5-encoded isoenzymes can decarboxylate branched-chain 2-oxo acids. To
      investigate whether pyruvate decarboxylase is essential for fusel alcohol
      production by whole cells, wild-type S. cerevisiae and an isogenic pyruvate
      decarboxylase-negative strain were grown on ethanol with a mixture of leucine,
      isoleucine, and valine as the nitrogen source. Surprisingly, the three
      corresponding fusel alcohols were produced in both strains. This result proves
      that decarboxylation of branched-chain 2-oxo acids via pyruvate decarboxylase is
      not an essential step in fusel alcohol production.

PMID- 9546165
TI  - The Desulfuromonas acetoxidans triheme cytochrome c7 produced in Desulfovibrio
      desulfuricans retains its metal reductase activity.
AB  - Multiheme cytochrome c proteins that belong to class III have been recently shown
      to exhibit a metal reductase activity, which could be of great environmental
      interest, especially in metal bioremediation. To get a better understanding of
      these activities, the gene encoding cytochrome c7 from the sulfur-reducing
      bacterium Desulfuromonas acetoxidans was cloned from genomic DNA by PCR and
      expressed in Desulfovibrio desulfuricans G201. The expression system was based on
      the cyc transcription unit from Desulfovibrio vulgaris Hildenborough and led to
      the synthesis of holocytochrome c7 when transferred by electrotransformation into
      the sulfate reducer Desulfovibrio desulfuricans G201. The produced cytochrome was
      indistinguishable from the protein purified from Desulfuromonas acetoxidans cells
      with respect to several biochemical and biophysical criteria and exhibited the
      same metal reductase activities as determined from electrochemical experiments.
      This suggests that the molecule was correctly folded in the host organism.
      Desulfovibrio desulfuricans produces functional multiheme c-type cytochromes from
      bacteria belonging to a different genus and may be considered a suitable host for
      the heterologous biogenesis of multiheme c-type cytochromes for either structural
      or engineering studies. This report, which presents the first example of the
      transformation of a Desulfovibrio desulfuricans strain by electrotransformation,
      describes work that is the first necessary step of a protein engineering program
      that aims to specify the structural features that are responsible for the metal
      reductase activities of multiheme cytochrome c7.

PMID- 9546166
TI  - Detection of mRNA by reverse transcription-PCR as an indicator of viability in
      Escherichia coli cells.
AB  - The relationship between the detection of mRNA and cellular viability in
      Escherichia coli was investigated in cells killed by heat or ethanol. Reverse
      transcription-PCR (RT-PCR) methods were developed for detecting mRNA from rpoH,
      groEL, and tufA genes. mRNA from all three genes was detected immediately after
      the cells had been killed by heat or ethanol but gradually disappeared with time
      when dead cells were held at room temperature. In heat-killed cells, some mRNA
      targets became undetectable after 2 to 16 h, whereas after ethanol treatment,
      mRNA was still detected after 16 h. In contrast, 16S rRNA was detected by RT-PCR
      in all samples containing dead cells and did not disappear during a subsequent
      incubation of 16 h at room temperature. Of the different types of nucleic acid,
      mRNA is the most promising candidate for an indicator of viability in bacteria,
      but its persistence in dead cells depends on the inactivating treatment and
      subsequent holding conditions.

PMID- 9546167
TI  - Biodegradation of metal-EDTA complexes by an enriched microbial population.
AB  - A mixed culture utilizing EDTA as the sole carbon source was isolated from a
      mixed inoculum of water from the River Mersey (United Kingdom) and sludge from an
      industrial effluent treatment plant. Fourteen component organisms were isolated
      from the culture, including representatives of the genera Methylobacterium,
      Variovorax, Enterobacter, Aureobacterium, and Bacillus. The mixed culture
      biodegraded metal-EDTA complexes slowly; the biodegradability was in the order Fe
      > Cu > Co > Ni > Cd. By incorporation of inorganic phosphate into the medium as a
      precipitant ligand, heavy metals were removed in parallel to EDTA degradation.
      The mixed culture also utilized a number of possible EDTA degradation
      intermediates as carbon sources.

PMID- 9546168
TI  - A competitive microflora increases the resistance of Salmonella typhimurium to
      inimical processes: evidence for a suicide response.
AB  - The presence of a viable competitive microflora at cell densities of 10(8) CFU ml
      1 protects an underlying population of 10(5) CFU of Salmonella typhimurium ml-1
      against freeze injury. The mechanism of enhanced resistance was initially
      postulated to be via an RpoS-mediated adaptive response. By using an spvRA::
      luxCDABE reporter we have shown that although the onset of RpoS-mediated gene
      expression was brought forward by the addition of a competitive microflora, the
      time taken for induction was measured in hours. Since the protective effect of a
      competitive microflora is essentially instantaneous, the stationary-phase
      adaptive response is excluded as the physiological mechanism. The only
      instantaneous effect of the competitive microflora was a reduction in the percent
      saturation of oxygen from 100% to less than 10%. For both mild heat treatment (55
      degrees C) and freeze injury this change in oxygen tension affords Salmonella a
      substantive (2 orders of magnitude) enhancement in survival. By reducing the
      levels of dissolved oxygen through active respiration, a competitive microflora
      reduces oxidative damage to exponential-phase cells irrespective of the inimical
      treatment. These results have led us to propose a suicide hypothesis for the
      destruction of rapidly growing cells by inimical processes. In essence, the
      suicide hypothesis proposes that a mild inimical process leads to the growth
      arrest of exponential-phase cells and to the decoupling of anabolic and catabolic
      metabolism. The result of this is a free radical burst which is lethal to
      unadapted cells.

PMID- 9546169
TI  - Bacterial oxidation of mercury metal vapor, Hg(0).
AB  - We used metalloregulated luciferase reporter fusions and spectroscopic
      quantification of soluble Hg(II) to determine that the hydroperoxidase-catalase,
      KatG, of Escherichia coli can oxidize monatomic elemental mercury vapor, Hg(0),
      to the water-soluble, ionic form, Hg(II). A strain with a mutation in katG and a
      strain overproducing KatG were used to demonstrate that the amount of Hg(II)
      formed is proportional to the catalase activity. Hg(0) oxidation was much
      decreased in stationary-phase cells of a strain lacking KatG, suggesting that the
      monofunctional hydroperoxidase KatE is less effective at this reaction.
      Unexpectedly, Hg(0) oxidation also occurred in a strain lacking both KatE and
      KatG, suggesting that activities other than hydroperoxidases may carry out this
      reaction. Two typical soil bacteria, Bacillus and Streptomyces, also oxidize
      Hg(0) to Hg(II). These observations establish for the first time that bacteria
      can contribute, as do mammals and plants, to the oxidative phase of the global Hg
      cycle.

PMID- 9546171
TI  - Buffering capacity and membrane H+ conductance of neutrophilic and alkalophilic
      gram-positive bacteria.
AB  - Buffering capacity and membrane H+ conductance were examined in three gram
      positive bacteria, Staphylococcus aureus, Bacillus subtilis, and Bacillus
      alcalophilus. An acid pulse technique was used to measure both parameters. The
      buffering capacity and membrane H+ conductance of B. alcalophilus are influenced
      by the pH of the medium and the culture conditions. Suspensions of B.
      alcalophilus cells from both H. A. medium and L-malate medium cultures grown at
      pH 10.5 exhibited higher values for these parameters than cells grown at pH 8.5.
      B. alcalophilus grown aerobically had a lower buffering capacity and a lower
      membrane conductance for protons than the neutrophilic bacteria S. aureus and B.
      subtilis. Fermenting cells exhibited significantly higher values for both
      variables than respiring cells.

PMID- 9546170
TI  - A novel sensitive bioassay for detection of Bacillus cereus emetic toxin and
      related depsipeptide ionophores.
AB  - Of the toxins produced by Bacillus cereus, the emetic toxin is likely the most
      dangerous but, due to the lack of a suitable assay, the least well known. In this
      paper, a new, sensitive, inexpensive, and rapid bioassay for detection of the
      emetic toxin of B. cereus is described. The assay is based on the loss of
      motility of boar spermatozoa upon 24 h of exposure to extracts of emetic B.
      cereus strains or contaminated food. The paralyzed spermatozoa exhibited swollen
      mitochondria, but no depletion of cellular ATP or damage to plasma membrane
      integrity was observed. Analysis of the purified toxin by electrospray tandem
      mass spectrometry showed that it was a dodecadepsipeptide with a mass
      fragmentation pattern similar to that described for cereulide. The 50% effective
      concentration of the purified toxin to boar spermatozoa was 0.5 ng of purified
      toxin ml of extended boar semen-1. This amount corresponds to 10(4) to 10(5) CFU
      of B. cereus cells. No toxicity was detected for 27 other B. cereus strains up to
      10(8) CFU ml-1. The detection limit for food was 3 g of rice containing 10(6) to
      10(7) CFU of emetic B. cereus per gram. Effects similar to those provoked by
      emetic B. cereus toxin were also induced in boar spermatozoa by valinomycin and
      gramicidin at 2 and 3 ng ml of extended boar semen-1, respectively. The symptoms
      provoked by the toxin in spermatozoa indicated that B. cereus emetic toxin was
      acting as a membrane channel-forming ionophore, damaging mitochondria and
      blocking the oxidative phosphorylation required for the motility of boar
      spermatozoa.

PMID- 9546172
TI  - Pichia stipitis genes for alcohol dehydrogenase with fermentative and respiratory
      functions.
AB  - Two genes coding for isozymes of alcohol dehydrogenase (ADH); designated PsADH1
      and PsADH2, have been identified and isolated from Pichia stipitis CBS 6054
      genomic DNA by Southern hybridization to Saccharomyces cerevisiae ADH genes, and
      their physiological roles have been characterized through disruption. The amino
      acid sequences of the PsADH1 and PsADH2 isozymes are 80.5% identical to one
      another and are 71.9 and 74.7% identical to the S. cerevisiae ADH1 protein. They
      also show a high level identity with the group I ADH proteins from Kluyveromyces
      lactis. The PsADH isozymes are presumably localized in the cytoplasm, as they do
      not possess the amino-terminal extension of mitochondrion-targeted ADHs. Gene
      disruption studies suggest that PsADH1 plays a major role in xylose fermentation
      because PsADH1 disruption results in a lower growth rate and profoundly greater
      accumulation of xylitol. Disruption of PsADH2 does not significantly affect
      ethanol production or aerobic growth on ethanol as long as PsADH1 is present. The
      PsADH1 and PsADH2 isozymes appear to be equivalent in the ability to convert
      ethanol to acetaldehyde, and either is sufficient to allow cell growth on
      ethanol. However, disruption of both genes blocks growth on ethanol. P. stipitis
      strains disrupted in either PsADH1 or PsADH2 still accumulate ethanol, although
      in different amounts, when grown on xylose under oxygen-limited conditions. The
      PsADH double disruptant, which is unable to grow on ethanol, still produces
      ethanol from xylose at about 13% of the rate seen in the parental strain. Thus,
      deletion of both PsADH1 and PsADH2 blocks ethanol respiration but not production,
      implying a separate path for fermentation.

PMID- 9546173
TI  - Oxygen-dependent regulation of the expression of the catalase gene katA of
      Lactobacillus sakei LTH677.
AB  - The catalase gene katA of Lactobacillus sakei LTH677 was cloned and expressed in
      Escherichia coli UM2, Lactobacillus casei LK1, and Lactobacillus curvatus
      LTH1432. The last host is a catalase-deficient plasmid-cured derivative of a
      starter organism used in meat fermentation. The regulation of katA expression was
      found to be the same in L. sakei LTH677 and the recombinant strains. The addition
      of H2O2 to anaerobic cultures, as well as a switch to aerobic conditions,
      resulted in a strong increase in KatA activity. The expression was investigated
      in more detail with L. sakei LTH677 and L. curvatus LTH4002. The recombinant
      strain LTH4002 did not accumulate H2O2 under glucose-limited aerobic conditions
      and remained viable in the stationary phase. Under inductive conditions, the katA
      specific mRNA and the apoenzyme were synthesized de novo. Deletion derivatives of
      the katA promoter were produced, and the regulatory response was investigated by
      fusion to the beta-glucuronidase reporter gene gusA and expression in L. sakei
      LTH677. The fact that gene expression was subject to induction was confirmed at
      the level of transcription and protein synthesis. A small putative regulatory
      sequence of at least 25 bp was identified located upstream of the -35 site.
      Competition experiments performed with L. sakei LTH677 harboring the fusion
      constructs consisting of the katA promoter and gusA revealed that an activator
      protein is involved in the transcriptional induction of katA.

PMID- 9546174
TI  - Purification and characterization of a nylon-degrading enzyme.
AB  - A nylon-degrading enzyme found in the extracellular medium of a ligninolytic
      culture of the white rot fungus strain IZU-154 was purified by ion-exchange
      chromatography, gel filtration chromatography, and hydrophobic chromatography.
      The characteristics of the purified protein (i.e., molecular weight, absorption
      spectrum, and requirements for 2,6-dimethoxyphenol oxidation) were identical to
      those of manganese peroxidase, which was previously characterized as a key enzyme
      in the ligninolytic systems of many white rot fungi, and this result led us to
      conclude that nylon degradation is catalyzed by manganese peroxidase. However,
      the reaction mechanism for nylon degradation differed significantly from the
      reaction mechanism reported for manganese peroxidase. The nylon-degrading
      activity did not depend on exogenous H2O2 but nevertheless was inhibited by
      catalase, and superoxide dismutase inhibited the nylon-degrading activity
      strongly. These features are identical to those of the peroxidase-oxidase
      reaction catalyzed by horseradish peroxidase. In addition, alpha-hydroxy acids
      which are known to accelerate the manganese peroxidase reaction inhibited the
      nylon-degrading activity strongly. Degradation of nylon-6 fiber was also
      investigated. Drastic and regular erosion in the nylon surface was observed,
      suggesting that nylon is degraded to soluble oligomers and that nylon is degraded
      selectively.

PMID- 9546176
TI  - Longitudinal study of Escherichia coli O157:H7 dissemination on four dairy farms
      in Wisconsin.
AB  - A 14-month longitudinal study was conducted on four dairy farms (C, H, R, and X)
      in Wisconsin to ascertain the source(s) and dissemination of Escherichia coli
      O157:H7. A cohort of 15 heifer calves from each farm were sampled weekly by
      digital rectal retrieval from birth to a minimum of 7 months of age (range, 7 to
      13 months). Over the 14 months of the study, the cohort heifers and other
      randomly selected cattle from farms C and H tested negative. Farm R had two
      separate periods of E. coli O157:H7 shedding lasting 4 months (November 1995 to
      February 1996) and 1 month (July to August 1996), while farm X had at least one
      positive cohort animal for a 5-month period (May to October 1996). Heifers shed
      O157:H7 strains in feces for 1 to 16 weeks at levels ranging from 2.0 x 10(2) to
      8.7 x 10(4) CFU per g. E. coli O157:H7 was also isolated from other noncohort
      cattle, feed, flies, a pigeon, and water associated with the cohort heifers on
      farms R and/or X. When present in animal drinking water, E. coli O157:H7
      disseminated through the cohort cattle and other cattle that used the water
      source. E. coli O157:H7 was found in water at < 1 to 23 CFU/ml. Genomic subtyping
      by pulsed-field gel electrophoresis demonstrated that a single O157:H7 strain
      comprised a majority of the isolates from cohort and noncohort cattle, water, and
      other positive samples (i.e., from feed, flies, and a pigeon, etc.) on a farm.
      The isolates from farm R displayed two predominant XbaI restriction endonuclease
      digestion profiles (REDP), REDP 3 and REDP 7, during the first and second periods
      of shedding, respectively. Six additional REDP that were > or = 89% similar to
      REDP 3 or REDP 7 were identified among the farm R isolates. Additionally, the
      REDP of an O157:H7 isolate from a heifer on farm R in 1994 was indistinguishable
      from REDP 3. Farm X had one O157:H7 strain that predominated (96% of positive
      samples had strains with REDP 9), and the REDP of an isolate from a heifer in
      1994 was indistinguishable from REDP 9. These results suggest that E. coli
      O157:H7 is disseminated from a common source on farms and that strains can
      persist in a herd for a 2-year period.

PMID- 9546177
TI  - COVASIAM: an image analysis method that allows detection of confluent microbial
      colonies and colonies of various sizes for automated counting.
AB  - In this work we introduce the confluent and various sizes image analysis method
      (COVASIAM), an automated colony count technique that uses digital imaging
      technology for detection and separation of confluent microbial colonies and
      colonies of various sizes growing on petri dishes. The proposed method takes
      advantage of the optical properties of the surfaces of most microbial colonies.
      Colonies in the petri dish are epi-illuminated in order to direct the reflection
      of concentrated light coming from a halogen lamp towards an image-sensing device.
      In conjunction, a multilevel threshold algorithm is proposed for colony
      separation and counting. These procedures improved the quantification of colonies
      showing confluence or differences in size. We tested COVASIAM with a sample set
      of microorganisms that form colonies with contrasting physical properties:
      Saccharomyces cerevisiae, Aspergillus nidulans, Escherichia coli, Azotobacter
      vinelandii, Pseudomonas aeruginosa, and Rhizobium etli. These physical properties
      range from smooth to hairy, from bright to opaque, and from high to low
      convexities. COVASIAM estimated an average of 95.47% (sigma = 8.55%) of the
      manually counted colonies, while an automated method based on a single-threshold
      segmentation procedure estimated an average of 76% (sigma = 16.27) of the
      manually counted colonies. This method can be easily transposed to almost every
      image-processing analyzer since the procedures to compile it are generically
      standard.

PMID- 9546178
TI  - Structural and kinetic properties of nonglycosylated recombinant Penicillium
      amagasakiense glucose oxidase expressed in Escherichia coli.
AB  - The gene coding for Penicillium amagasakiense glucose oxidase (GOX; beta-D
      glucose; oxygen 1-oxidoreductase [EC 1.1.3.4]) has been cloned by PCR
      amplification with genomic DNA as template with oligonucleotide probes derived
      from amino acid sequences of N- and C-terminal peptide fragments of the enzyme.
      Recombinant Escherichia coli expression plasmids have been constructed from the
      heat-induced pCYTEXP1 expression vector containing the mature GOX coding
      sequence. When transformed into E. coli TG2, the plasmid directed the synthesis
      of 0.25 mg of protein in insoluble inclusion bodies per ml of E. coli culture
      containing more than 60% inactive GOX. Enzyme activity was reconstituted by
      treatment with 8 M urea and 30 mM dithiothreitol and subsequent 100-fold dilution
      to a final protein concentration of 0.05 to 0.1 mg ml-1 in a buffer containing
      reduced glutathione-oxidized glutathione, flavin adenine dinucleotide, and
      glycerol. Reactivation followed first-order kinetics and was optimal at 10
      degrees C. The reactivated recombinant GOX was purified to homogeneity by mild
      acidification and anion-exchange chromatography. Up to 12 mg of active GOX could
      be purified from a 1-liter E. coli culture. Circular dichroism demonstrated
      similar conformations for recombinant and native P. amagasakiense GOXs. The
      purified enzyme has a specific activity of 968 U mg-1 and exhibits kinetics of
      glucose oxidation similar to those of, but lower pH and thermal stabilities than,
      native GOX from P. amagasakiense. In contrast to the native enzyme, recombinant
      GOX is nonglycosylated and contains a single isoform of pI 4.5. This is the first
      reported expression of a fully active, nonglycosylated form of a eukaryotic,
      glycosylated GOX in E. coli.

PMID- 9546181
TI  - Use of 13C nuclear magnetic resonance to assess fossil fuel biodegradation: fate
      of [1-13C]acenaphthene in creosote polycyclic aromatic compound mixtures degraded
      by bacteria.
AB  - [1-13C]acenaphthene, a tracer compound with a nuclear magnetic resonance (NMR)
      active nucleus at the C-1 position, has been employed in conjunction with a
      standard broad-band-decoupled 13C-NMR spectroscopy technique to study the
      biodegradation of acenaphthene by various bacterial cultures degrading aromatic
      hydrocarbons of creosote. Site-specific labeling at the benzylic position of
      acenaphthene allows 13C-NMR detection of chemical changes due to initial
      oxidations catalyzed by bacterial enzymes of aromatic hydrocarbon catabolism.
      Biodegradation of [1-13C]acenaphthene in the presence of naphthalene or creosote
      polycyclic aromatic compounds (PACs) was examined with an undefined mixed
      bacterial culture (established by enrichment on creosote PACs) and with isolates
      of individual naphthalene- and phenanthrene-degrading strains from this culture.
      From 13C-NMR spectra of extractable materials obtained in time course
      biodegradation experiments under optimized conditions, a number of signals were
      assigned to accumulated products such as 1-acenaphthenol, 1-acenaphthenone,
      acenaphthene-1,2-diol and naphthalene 1,8-dicarboxylic acid, formed by benzylic
      oxidation of acenaphthene and subsequent reactions. Limited degradation of
      acenaphthene could be attributed to its oxidation by naphthalene 1,2-dioxygenase
      or related dioxygenases, indicative of certain limitations of the undefined mixed
      culture with respect to acenaphthene catabolism. Coinoculation of the mixed
      culture with cells of acenaphthene-grown strain Pseudomonas sp. strain A2279
      mitigated the accumulation of partial transformation products and resulted in
      more complete degradation of acenaphthene. This study demonstrates the value of
      the stable isotope labeling approach and its ability to reveal incomplete
      mineralization even when as little as 2 to 3% of the substrate is incompletely
      oxidized, yielding products of partial transformation. The approach outlined may
      prove useful in assessing bioremediation performance.

PMID- 9546179
TI  - Molecular cloning and transcriptional regulation of the Aspergillus nidulans xlnD
      gene encoding a beta-xylosidase.
AB  - The xlnD gene encoding the 85-kDa beta-xylosidase was cloned from Aspergillus
      nidulans. The deduced primary structure of the protein exhibits considerable
      similarity to the primary structures of the Aspergillus niger and Trichoderma
      reesei beta-xylosidases and some similarity to the primary structures of the
      class 3 beta-glucosidases. xlnD is regulated at the transcriptional level; it is
      induced by xylan and D-xylose and is repressed by D-glucose. Glucose repression
      is mediated by the product of the creA gene. Although several binding sites for
      the pH regulatory protein PacC were found in the upstream regulatory region, it
      was not clear from a Northern analysis whether PacC is involved in
      transcriptional regulation of xlnD.

PMID- 9546182
TI  - Influence of water temperature and salinity on Vibrio vulnificus in Northern Gulf
      and Atlantic Coast oysters (Crassostrea virginica).
AB  - This study investigated the temperature and salinity parameters associated with
      waters and oysters linked to food-borne Vibrio vulnificus infections. V.
      vulnificus was enumerated in oysters collected at three northern Gulf Coast sites
      and two Atlantic Coast sites from July 1994 through September 1995. Two of these
      sites, Black Bay, La., and Apalachicola Bay, Fla., are the source of the majority
      of the oysters implicated in V. vulnificus cases. Oysters in all Gulf Coast sites
      exhibited a similar seasonal distribution of V. vulnificus: a consistently large
      number (median concentration, 2,300 organisms [most probable number] per g of
      oyster meat) from May through October followed by a gradual reduction during
      November and December to < or = 10 per g, where it remained from January through
      mid-March, and a sharp increase in late March and April to summer levels. V.
      vulnificus was undetectable (< 3 per g) in oysters from the North and South
      Carolina sites for most of the year. An exception occurred when a late-summer
      flood caused a drop in salinity in the North Carolina estuary, apparently causing
      V. vulnificus numbers to increase briefly to Gulf Coast levels. At Gulf Coast
      sites, V. vulnificus numbers increased with water temperatures up to 26 degrees C
      and were constant at higher temperatures. High V. vulnificus levels (> 10(3) per
      g) were typically found in oysters from intermediate salinities (5 to 25 ppt).
      Smaller V. vulnificus numbers (< 10(2) per g) were found at salinities above 28
      ppt, typical of Atlantic Coast sites. On 11 occasions oysters were sampled at
      times and locations near the source of oysters implicated in 13 V. vulnificus
      cases; the V. vulnificus levels and environmental parameters associated with
      these samples were consistent with those of other study samples collected from
      the Gulf Coast from April through November. These findings suggest that the
      hazard of V. vulnificus infection is not limited to brief periods of unusual
      abundance of V. vulnificus in Gulf Coast oysters or to environmental conditions
      that are unusual to Gulf Coast estuaries.

PMID- 9546184
TI  - Cocoa fermentations conducted with a defined microbial cocktail inoculum.
AB  - Cocoa fermentations were performed in wooden boxes under the following four
      experimental regimens: beans naturally fermented with wild microflora;
      aseptically prepared beans with no inoculum; and beans inoculated with a defined
      cocktail containing microorganisms at a suitable concentration either at zero
      time or by using phased additions at appropriate times. The cocktail used
      consisted of a yeast, Saccharomyces cerevisiae var. chevalieri, two lactic acid
      bacterial species, Lactobacillus lactis and Lactobacillus plantarum, and two
      acetic acid bacterial species, Acetobacter aceti and Gluconobacter oxydans subsp.
      suboxydans. The parameters measured were cell counts (for yeasts, filamentous
      fungi, lactic acid bacteria, acetic acid bacteria, and spore formers, including
      reisolation and identification of all residual cell types), sugar, ethanol,
      acetic acid, and lactic acid contents (and contents of other organic acids), pH,
      and temperature. A cut test for bean quality and a sensorial analysis of
      chocolate made from the beans were also performed. The natural fermentation
      mimicked exactly the conditions in 800-kg boxes on farms. The aseptic box
      remained largely free of microflora throughout the study, and no significant
      biochemical changes occurred. With the zero-time inoculum the fermentation was
      almost identical to the natural fermentation. The fermentation with the phased
      addition inoculum was similar, but many changes in parameters were slower and
      less pronounced, which led to a slightly poorer end product. The data show that
      the nearly 50 common species of microorganisms found in natural fermentations can
      be replaced by a judicious selection and concentration of members of each
      physiological group. This is the first report of successful use of a defined,
      mixed starter culture in such a complex fermentation, and it should lead to
      chocolate of more reliable and better quality.

PMID- 9546183
TI  - Gene cloning, transcriptional analysis, purification, and characterization of
      phenolic acid decarboxylase from Bacillus subtilis.
AB  - Bacillus subtilis displays a substrate-inducible decarboxylating activity with
      the following three phenolic acids: ferulic, p-coumaric, and caffeic acids. Based
      on DNA sequence homologies between the Bacillus pumilus ferulate decarboxylase
      gene (fdc) (A. Zago, G. Degrassi, and C. V. Bruschi, Appl. Environ. Microbiol.
      61:4484-4486, 1995) and the Lactobacillus plantarum p-coumarate decarboxylase
      gene (pdc) (J.-F. Cavin, L. Barthelmebs, and C. Divies, Appl. Environ. Microbiol.
      63:1939-1944, 1997), a DNA probe of about 300 nucleotides for the L. plantarum
      pdc gene was used to screen a B. subtilis genomic library in order to clone the
      corresponding gene in this bacterium. One clone was detected with this
      heterologous probe, and this clone exhibited phenolic acid decarboxylase (PAD)
      activity. The corresponding 5-kb insertion was partially sequenced and was found
      to contain a 528-bp open reading frame coding for a 161-amino-acid protein
      exhibiting 71 and 84% identity with the pdc- and fdc-encoded enzymes,
      respectively. The PAD gene (pad) is transcriptionally regulated by p-coumaric,
      ferulic, or caffeic acid; these three acids are the three substrates of PAD. The
      pad gene was overexpressed constitutively in Escherichia coli, and the stable
      purified enzyme was characterized. The difference in substrate specificity
      between this PAD and other PADs seems to be related to a few differences in the
      amino acid sequence. Therefore, this novel enzyme should facilitate
      identification of regions involved in catalysis and substrate specificity.

PMID- 9546185
TI  - Targeted mutants of Cochliobolus carbonum lacking the two major extracellular
      polygalacturonases.
AB  - The filamentous fungus Cochliobolus carbonum produces endo-alpha 1,4
      polygalacturonase (endoPG), exo-alpha 1,4-polygalacturonase (exoPG), and pectin
      methylesterase when grown in culture on pectin. Residual activity in a pgn1
      mutant (lacking endoPG) was due to exoPG activity, and the responsible protein
      has now been purified. After chemical deglycosylation, the molecular mass of the
      purified protein decreased from greater than 60 to 45 kDa. The gene that encodes
      exoPG, PGX1, was isolated with PCR primers based on peptide sequences from the
      protein. The product of PGX1, Pgx1p, has a predicted molecular mass of 48 kDa, 12
      potential N-glycosylation sites, and 61% amino acid identity to an exoPG from the
      saprophytic fungus Aspergillus tubingensis. Strains of C. carbonum mutated in
      PGX1 were constructed by targeted gene disruption and by gene replacement. Growth
      of pgx1 mutant strains on pectin was reduced by ca. 20%, and they were still
      pathogenic on maize. A double pgn1/pgx1 mutant strain was constructed by
      crossing. The double mutant grew as well as the pgx1 single mutant on pectin and
      was still pathogenic despite having less than 1% of total wild-type PG activity.
      Double mutants retained a small amount of PG activity with the same cation
      exchange retention time as Pgn1p and also pectin methylesterase and a PG activity
      associated with the mycelium. Continued growth of the pgn1/pgx1 mutant on pectin
      could be due to one or more of these residual activities.

PMID- 9546186
TI  - Recovery of humic-reducing bacteria from a diversity of environments.
AB  - To evaluate which microorganisms might be responsible for microbial reduction of
      humic substances in sedimentary environments, humic-reducing bacteria were
      isolated from a variety of sediment types. These included lake sediments,
      pristine and contaminated wetland sediments, and marine sediments. In each of the
      sediment types, all of the humic reducers recovered with acetate as the electron
      donor and the humic substance analog, 2,6-anthraquinone disulfonate (AQDS), as
      the electron acceptor were members of the family Geobacteraceae. This was true
      whether the AQDS-reducing bacteria were enriched prior to isolation on solid
      media or were recovered from the highest positive dilutions of sediments in
      liquid media. All of the isolates tested not only conserved energy to support
      growth from acetate oxidation coupled to AQDS reduction but also could oxidize
      acetate with highly purified soil humic acids as the sole electron acceptor. All
      of the isolates tested were also able to grow with Fe(III) serving as the sole
      electron acceptor. This is consistent with previous studies that have suggested
      that the capacity for Fe(III) reduction is a common feature of all members of the
      Geobacteraceae. These studies demonstrate that the potential for microbial humic
      substance reduction can be found in a wide variety of sediment types and suggest
      that Geobacteraceae species might be important humic-reducing organisms in
      sediments.

PMID- 9546187
TI  - Extremely barophilic bacteria isolated from the Mariana Trench, Challenger Deep,
      at a depth of 11,000 meters.
AB  - Two strains of obligately barophilic bacteria were isolated from a sample of the
      world's deepest sediment, which was obtained by the unmanned deep-sea submersible
      Kaiko in the Mariana Trench, Challenger Deep, at a depth of 10,898 m. From the
      results of phylogenetic analysis based on 16S rRNA gene sequences, DNA-DNA
      relatedness study, and analysis of fatty acid composition, the first strain
      (DB21MT-2) appears to be most highly similar to Shewanella benthica and close
      relatives, and the second strain (DB21MT-5) appears to be closely related to the
      genus Moritella. The optimal pressure conditions for growth of these isolates
      were 70 MPa for strain DB21MT-2 and 80 MPa for strain DB21MT-5, and no growth was
      detected at pressures of less than 50 MPa with either strain. This is the first
      evidence of the existence of an extreme-barophile bacterium of the genus
      Moritella isolated from the deep-sea environment.

PMID- 9546188
TI  - Spatial patterns of alkaline phosphatase expression within bacterial colonies and
      biofilms in response to phosphate starvation.
AB  - The expression of alkaline phosphatase in response to phosphate starvation was
      shown to be spatially and temporally heterogeneous in bacterial biofilms and
      colonies. A commercial alkaline phosphatase substrate that generates a
      fluorescent, insoluble product was used in conjunction with frozen sectioning
      techniques to visualize spatial patterns of enzyme expression in both Klebsiella
      pneumoniae and Pseudomonas aeruginosa biofilms. Some of the expression patterns
      observed revealed alkaline phosphatase activity at the boundary of the biofilm
      opposite the place where the staining substrate was delivered, indicating that
      the enzyme substrate penetrated the biofilm fully. Alkaline phosphatase
      accumulated linearly with time in K. pneumoniae colonies transferred from high
      phosphate medium to low-phosphate medium up to specific activities of 50 mumol
      per min per mg of protein after 24 h. In K. pneumoniae biofilms and colonies,
      alkaline phosphatase was initially expressed in the region of the biofilm
      immediately adjacent to the carbon and energy source (glucose). In time, the
      region of alkaline phosphatase expression expanded inward until it spanned most,
      but not all, of the biofilm or colony depth. In contrast, expression of alkaline
      phosphatase in P. aeruginosa biofilms occurred in a thin, sharply delineated band
      at the biofilm-bulk fluid interface. In this case, the band of activity never
      occupied more than approximately one-sixth of the biofilm. These results are
      consistent with the working hypothesis that alkaline phosphatase expression
      patterns are primarily controlled by the local availability of either the carbon
      and energy source or the electron acceptor.

PMID- 9546189
TI  - Enterohemorrhagic Escherichia coli O157:H7 present in radish sprouts.
AB  - Using cultivation, immunofluorescence microscopy, and scanning electron
      microscopy, we demonstrated the presence of viable enterohemorrhagic Escherichia
      coli O157:H7 not only on the outer surfaces but also in the inner tissues and
      stomata of cotyledons of radish sprouts grown from seeds experimentally
      contaminated with the bacterium. HgCl2 treatment of the outer surface of the
      hypocotyl did not kill the contaminating bacteria, which emphasized the
      importance of either using seeds free from E. coli O157:H7 in the production of
      radish sprouts or heating the sprouts before they are eaten.

PMID- 9546190
TI  - Development of a direct in situ PCR method for detection of specific bacteria in
      natural environments.
AB  - We applied HNPP (2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate) to direct
      in situ PCR for the routine detection of specific bacterial cells at the single
      cell level. PCR was performed on glass slides with digoxigenin-labeled dUTP. The
      digoxigenin-labeled PCR products were detected with alkaline phosphatase-labeled
      antidigoxigenin antibody and HNPP which was combined with Fast Red TR. A bright
      red fluorescent signal was produced from conversion to HNP (dephosphorylated
      form) by alkaline phosphatase. We used the ECOL DNA primer set for amplification
      of ribosomal DNA of Escherichia coli to identify cells specifically at the single
      cell level in a bacterial mixture. High-contrast images were obtained under an
      epifluorescence microscope with in situ PCR. By image analysis, E. coli cells in
      polluted river water also were detected.

PMID- 9546191
TI  - An origin of transfer (oriT) on the conjugative element pRS01 from Lactococcus
      lactis subsp. lactis ML3.
AB  - Previous analysis of the Tra1 region of the conjugative element pRS01 from
      Lactococcus lactis subsp. lactis ML3 suggested that an origin of transfer (oriT)
      was present. Deletion derivatives of this cloned Tra1 region were assayed for
      mobilization in the presence of the wild-type pRS01 element in trans. The pRS01
      oriT was localized to a 446-nucleotide segment in the intergenic region between
      open reading frames ltrD and ltrE. Sequence analysis of this region revealed a
      cluster of direct and inverted repeat structures characteristic of oriT regions
      associated with other conjugative systems.

PMID- 9546193
TI  - High-pressure inactivation and sublethal injury of pressure-resistant Escherichia
      coli mutants in fruit juices.
AB  - The potential of high-pressure-resistant mutants of Escherichia coli to survive
      high-pressure pasteurization in fruit juices and in low-pH buffers was
      investigated. Treatments with up to 500 MPa of pressure caused only a limited
      direct inactivation of the mutants but resulted in an accelerated low-pH
      inactivation during subsequent storage.

PMID- 9546192
TI  - Transformation of Acinetobacter sp. strain BD413 by transgenic sugar beet DNA.
AB  - The ability of Acinetobacter sp. strain BD413(pFG4 delta nptII) to take up and
      integrate transgenic plant DNA based on homologous recombination was studied
      under optimized laboratory conditions. Restoration of nptII, resulting in
      kanamycin-resistant transformants, was observed with plasmid DNA, plant DNA, and
      homogenates carrying the gene nptII. Molecular analysis showed that some
      transformants not only restored the 317-bp deletion but also obtained additional
      DNA.

PMID- 9546194
TI  - Sonication-dependent electroporation of the erythromycin-producing bacterium
      Saccharopolyspora erythraea.
AB  - We report the development of an electrotransformation method applicable to all
      strains of Saccharopolyspora erythraea examined to date. Vegetatively grown
      mycelia were rendered electrocompetent by subjecting mycelial suspensions to
      ultrasound pulses. The protocol provides an alternative route for the
      introduction of DNA into filamentous microorganisms otherwise recalcitrant to
      transformation techniques.

PMID- 9546195
TI  - DNA sequence similarity between California isolates of Cryptosporidium parvum.
AB  - We evaluated whether nucleic acid amplification with primers specific for
      Cryptosporidium parvum followed by automated DNA sequence analysis of the PCR
      amplicons could differentiate between California isolates of C. parvum obtained
      from livestock, humans, and feral pigs. Almost complete sequence identity existed
      among the livestock isolates and between the livestock and human isolates. DNA
      sequences from feral pig isolates differed from those from livestock and humans
      by 1.0 to 1.2%. The reference sequence obtained by Laxer et al. (M. A. Laxer, B.
      K. Timblin, and R. J. Patel, Am. J. Trop. Med. Hyg. 45:688-694, 1991.) differed
      from California isolates of C. parvum by 1.8 to 3.2%. These data suggest that DNA
      sequence analysis of the amplicon of Laxer et al. does not allow for
      differentiation between various strains of C. parvum or that our collection of
      isolates obtained from various hosts from across California was limited to one
      strain of C. parvum.

PMID- 9546197
TI  - Catalytic mechanism of aldose reductase studied by the combined potentials of
      quantum mechanics and molecular mechanics.
AB  - The catalytic reduction of D-glyceraldehyde to glycerol by aldose reductase has
      been investigated with the combined potentials of quantum mechanics (QM) and
      molecular mechanics (MM) to resolve the question of whether Tyr48 or His110
      serves as the proton donor during catalysis. Site directed mutagenesis studies
      favor Tyr48 as the proton donor while the presence of a water channel linking the
      N delta 1 of His110 to the bulk solvent suggests that His110 is the proton donor.
      Utilizing the combined potentials of QM and MM, the binding mode of substrate D
      glyceraldehyde was investigated by optimizing the local geometry of Asp43, Lys77,
      Tyr48, His110 and NADPH at the active site of aldose reductase. Reaction pathways
      for the reduction of D-glyceraldehyde to glycerol were then constructed by
      treating both Tyr48 and His110 as proton donors. Comparison of energetics
      obtained from the reaction pathways suggests His110 to be the proton donor. Based
      on these findings, a reduction mechanism of D-glyceraldehyde to glycerol is
      described.

PMID- 9546196
TI  - Statistical analysis of data pertaining to complex state systems by stepwise
      regression with reformulated parameters; application to spectroscopically
      monitored hemoglobin oxygen binding data.
AB  - A method is described for the statistical analysis of data pertaining to complex
      state systems, based on the concept of reformulating the parameters describing
      the system as a hierarchy of interactions, and this method demonstrated on the
      analysis of spectroscopically monitored hemoglobin oxygen binding data [K. Imai,
      Biophys. Chem. 37 (1990) 197-210]. The concept of reformulation was first
      extended to state parameters other than delta G degree s, such as the extinction
      coefficients (epsilon s) associated with different ligation states during
      hemoglobin oxygen binding. The reformulated parameters are incrementally allowed
      to vary in the data fitting procedure, and the statistical significance of the
      added parameters tested by F and Kolmogorov-Smirnov tests. The result of this
      method is the minimal set of statistically significant parameters required to
      describe the data. The hierarchical nature of reformulated parameters allows the
      physical significance of the subset of statistically significant parameters to be
      discussed even when all reformulated terms may not be statistically significant.
      Applying this method to hemoglobin oxygen binding data with the reformulated
      Adair model demonstrated that at least two, and at most three, of the four
      reformulated Adair constants are statistically significant. A reformulated square
      model was found to give a statistically indistinguishable fit from the Adair
      model, with the statistically significant thermodynamic terms essentially those
      proposed by Linus Pauling in 1935. A change in delta epsilon with subsequent
      oxygen binding events was found to be significant in both models. These results
      are consistent with a model for hemoglobin oxygen binding where a subunit changes
      its conformation upon oxygen binding, and affects the conformation of adjacent
      subunits.

PMID- 9546198
TI  - The PHBH fold: not only flavoenzymes.
AB  - p-Hydroxybenzoate hydroxylase, D-amino acid oxidase, cholesterol oxidase and
      glucose oxidase form a family of structurally related flavoenzymes. Comparison of
      their three-dimensional structures reveal how the same FAD-binding scaffold has
      been employed to implement diverse active-site architectures, suited for
      different types of catalytic reactions. The substrate binding mode differs in
      each of these enzymes, with the catalytically relevant residues not located on
      homologous positions. A common feature is provided by the ability of these enzyme
      to bury their substrates beneath the protein surface. In D-amino acid oxidase and
      cholesterol oxidase, a loop forms a 'lid' controlling the active site
      accessibility, whereas in p-hydroxybenzoate hydroxylase is the flavin itself,
      which swings out to allow substrate binding. The crystallographic analysis has
      revealed that the GTP-dissociation inhibitor of RAB GTPases has a folding
      topology remarkably similar to p-hydroxybenzoate hydroxylase. This finding
      highlights the versatile nature of this folding topology, which in addition to
      flavin-dependent catalysis, is suited for diverse functions, such as the
      regulation of GTPases.

PMID- 9546199
TI  - Interaction of Doxorubicin with phospholipid monolayer and liposomes.
AB  - The effect of Doxorubicin which is (an anthracycline antibiotic with a broad
      spectrum of antitumor activity) on the monolayer and bilayer in the form of large
      Multilamellar Vesicles (MLV's) of Dipalmitoyl phosphatidylcholine (DPPC) were
      studied by means of monolayer techniques (surface pressure, penetration kinetics,
      and association constant) and light scattering technique. The monolayer technique
      showed that addition of DXR to a lipid film composed of (DPPC/CHOL/PEG-PE) at a
      molar ratio of (100:0:0) produced a less condensed Monolayer. In the (pie-A)
      curves, DXR induced shift towards larger area/molecule, where the area/molecule
      was shifted from 61 to 89 A2, and 116 A2 in the presence of 20 and 40 nM DXR,
      respectively. The three curves collapsed at a pressure pi = 45 mN/m. In
      penetration kinetics experiment (delta pi-t), the change in pressure with time
      was 8 and 14 mN/m for a DXR concentration of 20 and 40 nM, respectively, and the
      increase in surface pressure presented a plateau over a period of 30 min. The
      measured association constant (K) was found to be 5 x 10(5)/M. In the light
      scattering experiment, there was a shift of the transition temperature (Tm) of
      (MLV's) of the same composition of the monolayer towards a smaller value from
      40.5 degrees to 34.5 degrees C. Incorporation of CHOL and PEG-PE as DPPC/CHOL/PEG
      PE at a molar ratio of (100:20:0), (100:20:4) and (100:20:4) greatly counteracted
      the effect of DXR and made the lipid membrane more condense and rigid. Moreover,
      the penetration of DXR into the membrane was greatly reduced. There was a very
      small shift for the (pi-A) and (delta pi-t) curves, and the association constant
      of the drug for these different lipid compositions was greatly reduced down to
      2.5 x 10(5)/M and the transition temperature (Tm) was increased up to (42.5
      degrees C) in the presence of 40 nM DXR. Our results suggest that DXR has a great
      effect on the phospholipid membrane, and that addition of CHOL or PEG-PE to the
      phospholipid membrane causes stabilization for the membrane, and reduces the
      interaction with Doxorubicin.

PMID- 9546200
TI  - NMR triple-quantum filtered relaxation analysis of 17O-water in insulin
      solutions: an insight into the aggregation of insulin and the properties of its
      bound water.
AB  - Transverse triple-quantum filtered NMR spectroscopy (TTQF) of 17O-water was used
      to study the properties of water in insulin solutions at different Zn2+
      concentrations and pH values. It was established that strongly bound water
      molecules are already present in Zn-free insulin. On the assumption that the
      effective correlation time of a strongly bound water molecule, tau sb, is 10 ns,
      the apparent number of strongly bound water molecules was approximately 3 to 4
      per insulin monomer. Addition of Zn2+ equivalent to approximately 2 g-atoms per
      hexamer did not produce substantial increases in the overall 17O-water TTQF
      signal intensity and apparent fraction of bound water. The dramatic enhancement
      of the TTQF signals observed for samples with a Zn2+/hexamer ratio greater than
      approximately 2:1 could be attributed to the increase in correlation time of the
      strongly bound water, due to the formation of higher-order oligomers of the
      protein.

PMID- 9546201
TI  - Staggered movement of an actin filament sliding on myosin molecules in the
      presence of ATP.
AB  - An actin filament sliding on myosin molecules in the presence of an extremely low
      concentration of ATP exhibited a staggered movement. Longitudinally sliding
      movement of the filament was frequently interrupted by its non-sliding,
      fluctuating movements both in the longitudinal and transversal directions.
      Intermittent sliding movements of an actin filament indicate establishment of a
      coordination of ATP-mediated active sites distributed along the filament.

PMID- 9546202
TI  - Irreversible thermal denaturation of uridine phosphorylase from Escherichia coli
      K-12.
AB  - Thermal denaturation of uridine phosphorylase from Escherichia coli K-12 has been
      studied by differential scanning calorimetry. The excess heat capacity vs.
      temperature profiles were obtained at temperature scanning rates of 0.25, 0.5,
      and 1 K/min. These profiles were analysed using three models of irreversible
      denaturation which are approximations to the whole Lumry-Eyring model, namely,
      the one-step model of irreversible denaturation, the Lumry-Eyring model with the
      fast equilibrating first step, and the model involving two consecutive
      irreversible steps. In terms of statistics the latter model describes the
      kinetics of thermal denaturation of uridine phosphorylase more satisfactorily
      than the two other models. The values of energy activation for the first and
      second steps calculated for the model involving two consecutive irreversible
      steps are the following: Ea,1 = 609.3 +/- 1.8 kJ/mol and Ea,2 = 446.8 +/- 3.2
      kJ/mol.

PMID- 9546204
TI  - Characterization of repetitive DNA sequences carrying 5S rDNA of the triploid
      ginbuna (Japanese silver crucian carp, Carassius auratus langsdorfi).
AB  - Repetitive DNA sequences (Hi-b; 209 bp in length) were isolated from the HindIII
      digests of the genomic DNA of the triploid ginbuna, Carassius auratus langsdorfi.
      Sequence analyses revealed that the Hi-b repetitive units were comprised of the
      complete coding regions of 5S rDNA (120 bp in size) and their 5'flanking regions.
      The sequences of the Hi-b units from the same individual were highly homogeneous.
      Southern blot hybridization to the Hi-b probe displayed intricate patterns that
      represented the presence of other repetitive units containing the Hi-b related
      sequences. A major family of repetitive sequences related to the Hi-b was then
      obtained by the polymerase chain reaction using asymmetry primers for the 5S
      coding regions. These 331-bp sequences (AZ5S's) contained 5S pseudogenes as well
      as the almost entire Hi-b sequences, and seemed to be the true 5S rDNAs. The
      tandem arrangements of the AZ5S sequences explained most of the complex results
      of Southern blots. Another class of intriguing repeat units (Hi-b-beta and Hi-b
      gamma) were also isolated. Fluorescence in situ hybridization data revealed two
      major signals on a pair of homologous chromosomes and several minor signals on
      other chromosomes in the triploid ginbuna, indicating the existence of the 5S
      related sequences as several separate clusters. The major spots were shared with
      the tetraploid ginbuna and goldfish, but not with the diploid ginbuna. When the
      genomic organization of the Hi-b related sequences in other cyprinid fishes was
      examined, the hybridization patterns of the ginbuna were very similar to those of
      the goldfish, but were clearly different from those of the gengorobuna. The carp
      genome showed less complex patterns. Thus, the present 5S rDNA-related sequences
      could be candidates for phylogenetic molecular markers for the crucian carp.

PMID- 9546203
TI  - Germline cell formation in Drosophila embryogenesis.
AB  - The classical term germ cell determinant was defined to cover whole function of
      germ plasm, or morphologically remarkable cytoplasm localized in oocytes and germ
      cells. Since early 1970 consequential advances in technology, including
      microsurgery, genetic anatomy and gene manipulation, have allowed cytological and
      molecular analyses of pole plasm (germ plasm) in Drosophila embryos. A series of
      recent work has revealed that multiple factors or molecule species in pole plasm
      participate in a consecutive reactions resulting in germline formation. Two
      molecule species have been specified as playing roles in germline cell formation.
      One that participates in sequestering pole plasm from somatic environment is
      mitochondrial large ribosomal (mtlr) RNA, and the other involved in driving pole
      cells into the germline pathway is Nanos protein. Studies disclosed the roles of
      those two molecules are reviewed.

PMID- 9546205
TI  - Decreased physical performance of congenic mice with mismatch between the nuclear
      and the mitochondrial genome.
AB  - Maternal transmission of mitochondrial DNA (mtDNA) allows us to generate mtDNA
      congenic strain by repeating backcrosses of female mice to male mice of an inbred
      strain, which carries different mtDNA haplotype from that of the female
      progenitor. Since genetic backgrounds of inbred strains commonly used (e.g.,
      C57BL/6J [B6] and BALB/c) are mainly derived from an European subspecies of Mus
      musculus domesticus, congenic strains, in which mtDNA originated from an Asian
      subspecies M. musculus musculus or an European species M. spretus, give in vivo
      condition that mismatch occurs between the mitochondrial and the nuclear genome.
      So far, little has been known how the mismatch condition affects the
      physiological phenotype of the mice. To address this question, we established two
      mtDNA congenic strains, C57BL/6J(B6)-mtSPR and BALB/c-mtSHH, which carry M.
      spretus- and M. m. musculus-derived mtDNAs, representing the conditions of
      interspecific and intersubspecific mitochondrial-nuclear genome mismatch,
      respectively. Using these congenic strains, we examined their physical
      performance by measuring their running time on a treadmill belt until exhaustion.
      The result clearly showed that the mtDNA congenic strains manifested a
      significant decrease in the level of physical performance, when compared with
      their progenitor strains. It also appeared that the congenic mice manifested
      growth rate. Thus, all results indicated that mismatch between the mitochondrial
      and the nuclear genome causes phenotypic changes in individuals of mice.

PMID- 9546206
TI  - Characterization of the heterochromatic chromosome regions in sheep.
AB  - In order to elucidate the structural chromosome organization of the
      heterochromatic regions in sheep, we have used C-banding, silver-staining,
      sequential CDD technique and restriction endonuclease banding. By these banding
      techniques we obtained four fractions of repetitive DNA, the autosomal fractions
      A and B, the C fraction in the X chromosome, and the D fraction in the Y
      chromosome. Silver staining revealed active nucleolus organizer regions (NOR's)
      on the telomeric GC-rich areas of chromosomes 1, 2, 3, 4, and 25 which were
      digested with HaeIII restriction endonuclease.

PMID- 9546207
TI  - Drugs, money and deposition.

PMID- 9546209
TI  - Breaking up is easy with esters.
AB  - Formation of an internal (thio)ester bond activates numerous in vivo protein
      autoprocessing pathways including pyruvoyol group synthesis, autoproteolysis,
      protein splicing, enzyme activation and protein targeting. Structural analysis of
      precursors, intermediates and products is fine tuning our understanding of the
      mechanisms of these reactions.

PMID- 9546208
TI  - Oxidative modifications in nitrosative stress.
AB  - The molecular basis of redox sensitivity in proteins is not well understood. Here
      we consider a continuum of NO- and O2-related modifications of cysteine residues
      that constitute biological signaling events on the one hand and hallmarks of
      nitrosative and oxidative stresses on the other.

PMID- 9546210
TI  - All wrapped up.
AB  - How is it possible that nine small repeated 'zinc finger' units (each spanning
      just 3 or 4 base pairs) can protect the whole 50 base pair binding site of TFIIIA
      and why should such a periodic protein structure give rise to such an asymmetric
      footprint on DNA? The crystal structure of the first six fingers of TFIIIA bound
      to 31 base pairs of DNA explains everything: not all zinc fingers act alike.

PMID- 9546211
TI  - Ankyrin(g) ETS domains to DNA.

PMID- 9546212
TI  - The alpha and beta of turning on a molecular switch.
AB  - The crystal structures of RCC1 and the Sec7 domain of human Arno, nucleotide
      exchange factors for the Ras-related GTPases Ran and ARF, reveal two very
      different folds, the former a seven-bladed beta-propeller, the latter a capped
      right-handed superhelix. Both are also unrelated to the folds of Mss4 and
      elongation factor Ts, nucleotide exchange factors for Rab and elongation factor
      Tu.

PMID- 9546213
TI  - Recognition of DNA methylation by zinc fingers.

PMID- 9546214
TI  - Picture story. A long unwinding road.

PMID- 9546215
TI  - Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers.
AB  - Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular
      mechanisms by which it exerts its effects are largely unknown. Few physiologic
      target molecules of NO have been identified, and even for these, the
      modifications caused by NO remain uncharacterized. Human glutathione reductase
      (hGR), a central enzyme of cellular antioxidant defense, is inhibited by S
      nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two
      in vivo transport forms of NO. Here, crystal structures of hGR inactivated by
      GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme
      inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys 63
      is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas
      modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid (R
      SO2H). Our results illustrate that various forms of NO can mediate distinct
      chemistry, and that sulfhydryl oxidation must be considered as a major mechanism
      of NO action.

PMID- 9546216
TI  - Structure of a stereoregular phosphorothioate DNA/RNA duplex.
AB  - In this work, we present the first NMR solution structure of a DNA/RNA hybrid
      containing stereoregular Rp-phosphorothioate modifications of all DNA backbone
      linkages. The complex of the enzymatically synthesized phosphorothioate DNA
      octamer (all-Rp)-d(GCGTCAGG) and its complementary RNA r(CCUGACGC) was found to
      adopt an overall conformation within the A-form family. Most helical parameters
      and the sugar puckers of the DNA strand assume values intermediate between A- and
      B-form. The close structural similarity with the unmodified DNA/RNA hybrid of the
      same sequence may explain why both the natural and the sulfur-substituted complex
      can be recognized and digested by ribonuclease H.

PMID- 9546217
TI  - Capture of an early fusion-active conformation of HIV-1 gp41.
AB  - Using an inhibitory synthetic peptide (DP-178) from HIV-1 gp41, we have trapped
      HIV-1 envelope glycoprotein (Env) undergoing conformational changes during virus
      entry. Our data show that DP-178 binds gp41 and inhibits Env-mediated membrane
      fusion after gp120 interacts with cellular receptors, indicating that
      conformational changes involving the coiled coil domain of gp41 are required for
      entry. Capture of this fusion-active conformation of Env provides insights into
      the early events leading to Env-mediated membrane fusion.

PMID- 9546218
TI  - Hydrolysis of a slow cyclic thiophosphate substrate of RNase T1 analyzed by time
      resolved crystallography.
AB  - Here we present a time-resolved crystallographic analysis of the hydrolysis of
      exo (Sp) guanosine 2',3'-cyclophosphorothioate by RNase T1. The use of a slow
      substrate and fast crystallization methods made it possible to perform the study
      with conventional data-collection techniques. The results support the idea that
      the hydrolysis reaction proceeds through a mechanism that is the inverse of the
      transesterification reaction. In addition, the structures provide an explanation
      for the differential behavior of RNase T1 towards exo- and endo-cyclic
      thiophosphates.

PMID- 9546219
TI  - Unusual beta-sheet periodicity in small cyclic peptides.
AB  - Cyclic peptide homologs of gramicidin S containing 6, 8, 10, 12, 14 and 16
      residues were synthesized and characterized using circular dichroism (CD) and 1H
      NMR spectroscopy. Based on the three-dimensional structures generated from these
      data we have found strong evidence of a periodic sequence-length dependence on
      beta-sheet content. In particular, peptides of length 6, 10 and 14 residues
      exhibit a high beta-sheet content, while peptides of 8, 12 and 16 residues appear
      to exist as random coils. This unusual beta-sheet periodicity may have important
      implications in our understanding of beta-sheet formation and in the design of
      constrained beta-sheet and beta-hairpin mimics.

PMID- 9546220
TI  - Crystal structure of aspartate decarboxylase at 2.2 A resolution provides
      evidence for an ester in protein self-processing.
AB  - The structure of L-aspartate-alpha-decarboxylase from E. coli has been determined
      at 2.2 A resolution. The enzyme is a tetramer with pseudofour-fold rotational
      symmetry. The subunits are six-stranded beta-barrels capped by small alpha
      helices at each end. The active sites are located between adjacent subunits. The
      electron density provides evidence for catalytic pyruvoyl groups at three active
      sites and an ester at the fourth. The ester is an intermediate in the
      autocatalytic self-processing leading to formation of the pyruvoyl group. This
      unprecedented structure provides novel insights into the general phenomenon of
      protein processing.

PMID- 9546221
TI  - The crystal structure of Dps, a ferritin homolog that binds and protects DNA.
AB  - The crystal structure of Dps, a DNA-binding protein from starved E. coli that
      protects DNA from oxidative damage, has been solved at 1.6 A resolution. The Dps
      monomer has essentially the same fold as ferritin, which forms a 24-mer with 432
      symmetry, a hollow core and pores at the three-fold axes. Dps forms a dodecamer
      with 23 (tetrahedral) point group symmetry which also has a hollow core and pores
      at the three-folds. The structure suggests a novel DNA-binding motif and a
      mechanism for DNA protection based on the sequestration of Fe ions.

PMID- 9546222
TI  - Crystal structures of a nitric oxide transport protein from a blood-sucking
      insect.
AB  - The nitrophorins are heme-based proteins from the salivary glands of the blood
      sucking insect Rhodnius prolixus that deliver nitric oxide gas (NO) to the victim
      while feeding, resulting in vasodilation and inhibition of platelet aggregation.
      The nitrophorins also bind tightly to histamine, which is released by the host to
      induce wound healing. Here we present three crystal structures of nitrophorin 1
      (NP1): bound to cyanide, which binds in a manner similar to NO (2.3 A
      resolution); bound to histamine (2.0 A resolution); and bound to what appears to
      be NH3 from the crystallization solution (2.0 A resolution). The NP1 structures
      reveal heme to be sandwiched between strands of a lipocalin-like beta-barrel, and
      in an arrangement unlike any other gas-transport protein discovered to date. The
      heme is six-coordinate with a histidine (His 59) on the proximal side, and ligand
      in a spacious pocket on the distal side. The structures confirm that NO and
      histamine compete for the same binding pocket and become buried on binding. The
      dissociation constant for histamine binding was found to be 19 nM, approximately
      100-fold lower than that for NO.

PMID- 9546223
TI  - Crystal structure of the type-2 Cu depleted laccase from Coprinus cinereus at 2.2
      A resolution.
AB  - Laccase catalyses the oxidation of a variety of organic substrates coupled to the
      reduction of oxygen to water. It is widely believed to be the simplest
      representative of the ubiquitous blue multi-copper oxidase family. Laccase is
      implicated in a wide spectrum of biological activities and, in particular, plays
      a key role in morphogenesis, development and lignin metabolism in fungi and
      plants. The structure of laccase from the fungus Coprinus cinereus has been
      determined by X-ray crystallography at a resolution of 2.2 A. Laccase is a
      monomer composed of three cupredoxin-like beta-sandwich domains, similar to that
      found in ascorbate oxidase. In contrast to ascorbate oxidase, however, the
      mononuclear type-1 Cu site lacks the axial methionine ligand and so exhibits
      trigonal planar coordination, consistent with its elevated redox potential.
      Crucially, the structure is trapped in a Cu depleted form in which the putative
      type-2 Cu atom is completely absent, but in which the remaining type-1 and type-3
      Cu sites display full occupancy. Type-2 Cu depletion has unexpected consequences
      for the coordination of the remaining type-3 Cu atoms.

PMID- 9546224
TI  - Crystal structure of the hCASK PDZ domain reveals the structural basis of class
      II PDZ domain target recognition.
AB  - PDZ domain containing proteins assist formation of cell-cell junctions and
      localization of membrane protein receptors and ion channels. PDZ domains interact
      with the C-terminal residues of a particular target membrane protein. Based on
      their binding specificities and sequence homologies, PDZ domains fall into two
      classes. The first crystal structure of a class II PDZ domain, that of hCASK, has
      been solved by multi-wavelength anomalous dispersion phasing. Complex formation
      with the C-terminus of a neighboring non-crystallographically related PDZ domain
      reveals interactions between hCASK and its ligand. Class II PDZ domains differ
      from class I domains by formation of a second hydrophobic binding pocket. The C
      terminal carboxylate binding loop of the PDZ domain is structurally conserved in
      both classes suggesting a generalized carboxylate binding motif (h-Gly-h) where h
      is a hydrophobic residue.

PMID- 9546225
TI  - Vein graft surveillance: is graft revision without angiography justified and what
      criteria should be used?
AB  - PURPOSE: The objective of this study was to assess the accuracy of color-flow
      duplex surveillance parameters to detect infrainguinal vein graft stenoses and to
      investigate whether graft revision without angiography is justified. METHODS: In
      a prospective study in which three centers participated, the data of graft
      surveillance in 300 patients were analyzed. For the evaluation of surveillance
      criteria all patients underwent a digital subtraction angiography if a graft
      stenosis was suspected. To create a control group, in patients with normal grafts
      a consented digital subtraction angiography was performed also. From these data
      the accuracy of seven duplex and three ankle blood pressure-derived variables was
      assessed. The relation between various surveillance criteria and continued graft
      patency was determined with life table analysis with the transient state method.
      RESULTS: The mean follow-up period was 20 months (range, 1 to 40 months). At
      univariate and multivariate analysis the peak systolic velocity (PSV) ratio
      provided the best correlation with angiographic stenoses > or = 70% (PSV ratio
      cutoff 3.0: sensitivity 80%, specificity 84%). This finding did not differ
      between the participating centers. With life table methods it was demonstrated
      that the best combination of efficacy (limitation of the number of unnecessary
      revisions), safety (minimal number of correctable lesions missed), and reduction
      of angiograms was obtained by a two-parameter surveillance algorithm. This
      algorithm included a PSV ratio < 2.5 to delineate patients in whom a conservative
      approach without angiography or revision was appropriate, a PSV ratio > or = 4.0
      to indicate patients in whom vein graft revision without angiography could be
      scheduled, and a group with PSV ratios between 2.5 and 4.0 in whom angiography
      was to be performed to determine clinical management on the basis of the stenosis
      severity. This algorithm had a positive predictive value of 93% and a negative
      predictive value of 89%. In addition, it resulted in a reduction of the number of
      angiograms of 49% compared with a policy of angiographies in all patients with a
      PSV ratio > or = 2.5. CONCLUSIONS: The best criterion to identify a failing graft
      is the PSV ratio. With a two-parameter algorithm for vein graft surveillance, the
      incidence of unnecessary revisions and of missed high-grade lesions was
      acceptably low, whereas the number of angiograms was reduced by one half.

PMID- 9546226
TI  - Contralateral symptoms after unilateral intervention for peripheral occlusive
      disease.
AB  - OBJECTIVE: The objectives of this study were (1) to determine the incidence of
      contralateral symptoms in patients with a unilateral intervention for peripheral
      arterial occlusive disease and (2) to identify characteristics that predict these
      symptoms. SUBJECTS AND SETTING: We included patients who had a unilateral
      surgical or percutaneous intervention for peripheral arterial occlusive disease
      at the Brigham and Women's Hospital (Boston) between 1990 and 1995 (n = 532).
      MAIN OUTCOME MEASURE: The main outcome measure was the first occurrence of
      contralateral critical ischemia or intermittent claudication. RESULTS: The annual
      incidence rate of contralateral critical ischemia was considerable, ranging from
      3.3% to 8.3% during the first 4 years after the initial ipsilateral intervention.
      The annual incidence rate of contralateral critical ischemia and claudication
      combined varied from 7.7% to 21.3%. Cox regression analysis indicated that the
      initial ipsilateral symptoms and the initial contralateral ankle/brachial index
      can be used to predict the occurrence of contralateral symptoms. After correction
      was done for these two variables, we found no statistically significant effects
      for other factors including age, sex, diabetes, smoking, antihypertensive
      medication, history of coronary artery disease, the type of intervention, and the
      arterial level of the intervention. CONCLUSIONS: The results of our analysis
      emphasize that peripheral arterial occlusive disease is essentially a two-limb
      problem. Especially patients with previous ipsilateral critical ischemia and
      patients with a poor initial contralateral ankle/brachial index have a high risk
      for contralateral critical ischemia.

PMID- 9546227
TI  - Intermittent claudication: symptom severity versus health values.
AB  - OBJECTIVE: The objective of this study was to obtain health values from patients
      with intermittent claudication with five different instruments and to study the
      construct validity of these measures of health-related quality of life by
      examining their relation with symptom severity. METHODS: We included all patients
      with intermittent claudication who participated in an exercise program of the
      Department of Internal Medicine at our university hospital (n = 92). Health value
      instruments included the verbal rating scale, time trade-off, standard gamble,
      EuroQol, and the Health Utilities Index (Mark III). Symptom-free walking distance
      was used as a measure of symptom severity. RESULTS: For all instruments the
      average health values in groups of patients with a symptom-free walking distance
      < or = 150 m were lower than the average values in patients with a greater walk
      distance, but the differences for the time trade-off and the standard gamble were
      small, and only the differences for the verbal rating scale and the EuroQol were
      statistically significant. At the individual patient level considerable
      heterogeneity was seen, and the statistical association of the symptom-free
      walking distance with health values varied from poor to moderate (Spearman rank
      correlations, 0.03 to 0.48; p values, 0.003 to 0.78). CONCLUSION: At least for
      the verbal rating scale and the EuroQol, the results of our study provide
      evidence of the validity of the various health value instruments in a population
      of patients with peripheral arterial occlusive disease.

PMID- 9546228
TI  - The value of computed tomography in the assessment of suspected ruptured
      abdominal aortic aneurysm.
AB  - OBJECTIVE: The objective of this study was to determine the diagnostic value of
      computed tomography (CT) in patients with suspected ruptured abdominal aortic
      aneurysm. STUDY DESIGN: The study was an interrogation of a prospectively
      gathered computerized database. SETTING: The study was performed at a regional
      vascular surgery unit. SUBJECTS: Six hundred fifty-two consecutive patients were
      admitted to this unit with suspected ruptured abdominal aortic aneurysm between
      January 1, 1989, and December 31, 1996. Seventy-four patients (11.3%) in whom the
      diagnosis was in doubt on clinical grounds alone underwent urgent CT. A total of
      47 men and 27 women with a median age of 73 years (range, 52 to 86 years) were
      evaluated. MAIN OUTCOME MEASURES: CT and operative findings were compared.
      RESULTS: CT correctly diagnosed rupture in 22 of 28 patients who underwent
      operation and correctly excluded rupture in 30 of 39 patients who underwent
      operation. The sensitivity and specificity of CT when compared with operative
      findings were therefore 79% and 77%, respectively. CONCLUSIONS: These data
      indicate that CT has little additional diagnostic value. If in the opinion of an
      experienced vascular surgeon rupture cannot be excluded on clinical grounds
      alone, and the patient has no medical contraindications to abdominal aortic
      aneurysm repair, then the patient should be taken directly to the operating
      department.

PMID- 9546229
TI  - Anastomotic aneurysms after surgical treatment of Takayasu's arteritis: a 40-year
      experience.
AB  - PURPOSE: To evaluate the clinical characteristics of anastomotic aneurysms that
      develop in surgically treated patients with Takayasu's arteritis. METHODS: Among
      103 patients with Takayasu's arteritis treated surgically over 40 years, 91
      patients with 259 anastomoses (allowing for exclusion of 12 operative deaths)
      participated in follow-up study from 1 month to 37.3 years with a mean value +/-
      SEM of 17.3 +/- 1.1 years with a follow-up completion rate of 93% at 30 years.
      The clinical characteristics of anastomotic aneurysms were clarified, and the
      influences of several factors (sites of anastomoses, occlusive or aneurysmal
      disease, suture material, preoperative systemic inflammation, and administration
      of corticosteroids) on formation of anastomotic aneurysms were analyzed by means
      of life-table method and Cox regression analysis. RESULTS: Twenty-two uninfected
      anastomotic aneurysms were found among 14 patients (22 of 259 anastomoses, 8.5%).
      The interval between the previous operation and diagnosis varied from 1.6 to 30
      years with a mean value +/- SEM of 9.8 +/- 1.8 years. The cumulative incidence of
      anastomotic aneurysm at 20 years was 12.0%. Systemic inflammation or steroid
      administration had little influence on formation of anastomotic aneurysm.
      Instead, anastomotic aneurysm tended to occur after operations for aneurysmal
      lesions. CONCLUSIONS: Anastomotic aneurysm can occur anytime after operations for
      Takayasu's arteritis. The development of anastomotic aneurysm is not influenced
      by any factor specific to this disease except the presence of an aneurysmal
      lesion.

PMID- 9546230
TI  - Endoleak after endovascular graft repair of experimental aortic aneurysms: does
      coil embolization with angiographic "seal" lower intraaneurysmal pressure?
AB  - PURPOSE: To investigate the relation between endoleaks and intraaneurysmal
      pressure (IAP) and the effect of coil embolization in the management of
      endoleaks. METHODS: The infrarenal aorta of a dog (n = 15) was replaced by a
      polytetrafluoroethylene aneurysm containing a pressure transducer. Group I (n =
      4) had untreated aneurysms. Group II (n = 4) had endovascularly excluded
      aneurysms without an endoleak. Group III (n = 7) had aneurysms excluded by means
      of grafts with a defect that represented the source of an endoleak. After 4 weeks
      of follow-up study, the endoleaks in group III dogs were subjected to coil
      embolization. Systolic IAP was measured daily and expressed as a ratio of
      systolic blood pressure obtained from a forelimb cuff. Arteriography, duplex
      ultrasonography, and spiral contrast computed tomography were performed to
      evaluate endoleaks. RESULTS: In group I, the LAP remained close to systolic blood
      pressure (ratio of 0.96 +/- 0.06), whereas in group II the IAP ratio showed a
      decline to 0.34 +/- 0.16 (p = 0.0009 group I versus II). After an initial
      decrease, the IAP ratio in group III stabilized at 0.75 +/- 0.18 (p = 0.003,
      group II versus III). Aneurysms with an endoleak remained pulsatile with a pulse
      pressure of 30 +/- 16 mm Hg, which was less than that of untreated aneurysms (62
      +/- 15 mm Hg; p < 0.0001 group I versus III). Arteriography and computed
      tomography revealed "sealing" of endoleaks after coil embolization, but IAP ratio
      did not decrease (0.76 +/- 0.14) after coil embolization. CONCLUSIONS: Incomplete
      endovascular aneurysm exclusion caused by an endoleak fails to reduce IAP ratio
      and may subject the aneurysm to a continued risk for rupture. Although coil
      embolization resulted in angiographic and computed tomographic sealing, it failed
      to reduce IAP ratio.

PMID- 9546231
TI  - Ex vivo human carotid artery bifurcation stenting: correlation of lesion
      characteristics with embolic potential.
AB  - PURPOSE: To develop an ex vivo human carotid artery stenting model that can be
      used for the quantitative analysis of risk for embolization associated with
      balloon angioplasty and stenting and to correlate this risk with lesion
      characteristics to define lesions suitable for balloon angioplasty and stenting.
      METHODS: Specimens of carotid plaque (n = 24) were obtained circumferentially
      intact from patients undergoing standard carotid endarterectomy. Carotid lesions
      were prospectively characterized on the basis of angiographic and duplex findings
      before endarterectomy and clinical findings. Specimens were encased in a
      polytetrafluoroethylene wrap and mounted in a flow chamber that allowed access
      for endovascular procedures and observations. Balloon angioplasty and stenting
      were performed under fluoroscopic guidance with either a Palmaz stent or a
      Wallstent endoprosthesis. Ex vivo angiograms were obtained before and after
      intervention. Effluent from each specimen was filtered for released embolic
      particles, which were microscopically examined, counted, and correlated with
      various plaque characteristics by means of multivariate analysis. RESULTS:
      Balloon angioplasty and stenting produced embolic particles that consisted of
      atherosclerotic debris, organized thrombus, and calcified material. The number of
      embolic particles detected after balloon angioplasty and stenting was not related
      to preoperative symptoms, sex, plaque ulceration or calcification, or artery
      size. However, echolucent plaques generated a higher number of particles compared
      with echogenic plaques (p < 0.01). In addition, increased lesion stenosis also
      significantly correlated with the total number of particles produced by balloon
      angioplasty and stenting (r = 0.55). Multivariate analysis revealed that these
      two characteristics were independent risk factors. CONCLUSIONS: Echolucent
      plaques and plaques with stenosis > or = 90% produced a higher number of embolic
      particles and therefore may be less suitable for balloon angioplasty and
      stenting. This ex vivo model can be used to identify high-risk lesions for
      balloon angioplasty and stenting and can aid in the evaluation of new devices
      being considered for carotid balloon angioplasty and stenting.

PMID- 9546232
TI  - Duplex ultrasound in the hemodynamic evaluation of the late sequelae of deep
      venous thrombosis.
AB  - PURPOSE: The use of duplex ultrasound scanning to evaluate the hemodynamic
      outcome of deep venous thrombosis 7 to 13 years after the original diagnosis.
      METHODS: Duplex ultrasound was used to re-examine 1212 segments of vein from 72
      patients (49 men, 23 women) with deep venous thrombosis previously diagnosed by
      means of phlebography to detect reflux and obstruction and evaluate flow; 611
      segments were initially thrombosed and 601 segments were open. To define reflux,
      reversed flow in 31 healthy persons was measured. RESULTS: In a review of all
      veins of the 72 patients, 8 patients (11%) had completely normal duplex results
      in all veins, 33 (46%) had reflux, 6 (8%) had at least one noncompressible vein
      segment, and 25 (35%) had a combination of both. In the proximal vein segments
      without initial thrombosis a higher percentage was normal (73%) than in segments
      with initial thrombosis (46%). There was a significantly higher frequency of
      reflux (46%, p = 0.05) and noncompressibility (12%, p < 0.01) in initially
      thrombosed proximal vein segments than in vein segments without initial
      thrombosis (reflux 25%, noncompressibility 3%). Distal to the knee 125 (17%) of
      720 vein segments were not traceable. Significantly more initially thrombosed
      vein segments were not traceable (p < 0.01). In distal vein segments there was no
      significant difference in reflux (7% versus 5%) and noncompressibility (10%
      versus 5%) between vein segments with and without initial thrombosis. Flow was
      present in 99% of the 611 previously thrombosed proximal and distal segments.
      CONCLUSIONS: Most patients with deep venous thrombosis still had venous
      abnormalities 7 to 13 years after the initial diagnosis. The most common
      abnormality was reflux. Significantly more abnormalities were found in initially
      thrombosed segments. The abnormalities were found in the proximal vein segments
      and in the distal vein segments, although less frequently in the latter.

PMID- 9546233
TI  - Overestimation of a stenosis in the internal carotid artery by duplex sonography
      caused by an increase in volume flow.
AB  - PURPOSE: The accuracy of duplex sonography in predicting the degree of an
      internal carotid artery (ICA) stenosis is decreased when a contralateral high
      grade stenosis or occlusion is present. The purpose of this study was to
      determine whether this overestimation of the stenosis by duplex sonography is
      associated with an increase in volume flow through the ipsilateral ICA. METHODS:
      Forty-seven patients (89 vessels) with a symptomatic ICA stenosis or occlusion
      who underwent duplex sonography, intraarterial digital subtraction angiography,
      and magnetic resonance angiography flow quantification of the ICAs were
      evaluated. RESULTS: With the use of peak systolic velocity criteria, duplex
      overestimated stenoses more frequently (chi2: p = 0.03) in vessels with high
      volume flow (= mean volume flow in control group + 2 SD (>274 ml/min), 46%
      overestimation) than in vessels with normal or low volume flow (<274 ml/min, 20%
      overestimation). A correlation coefficient of 0.75 (p < 0.001) was found between
      volume flow and peak systolic velocity in the distal ICA, indicating that
      increased volume flow causes the peak systolic velocity to increase. Compared
      with volume flow in the control group (mean +/- SD = 198 +/- 38 ml/min), volume
      flow was increased in vessels with a 0% to 49% stenosis (mean +/- SD = 272 +/-
      100 ml/min, p < 0.05) and in vessels with a 50% to 69% stenosis (mean +/- SD =
      291 +/- 79 ml/min, p < 0.01) when the contralateral ICA had a 70% to 99% stenosis
      or occlusion. CONCLUSIONS: Increase in volume flow through the ICA frequently
      causes overestimation of stenoses in the ICA. Increased volume flow is frequently
      found in ICAs with a <70% stenosis that are contralateral to ICAs with a >70%
      stenosis or an occlusion.

PMID- 9546234
TI  - Validation of automated contour analysis of intravascular ultrasound images after
      vascular intervention.
AB  - PURPOSE: The purpose of this study was to determine the feasibility of automated
      contour analysis of intravascular ultrasound images obtained after vascular
      intervention. STUDY DESIGN: This was a descriptive study. METHODS: Intravascular
      ultrasound images obtained from patients after balloon angioplasty (n = 10),
      stent (n = 10), or stent graft placement (n = 10) were analyzed. A comparison was
      made between lumen area measured with an automated and a manual system. The
      location showing the smallest lumen area derived from the automated system was
      compared with the smallest lumen area selected by visual estimation. RESULTS:
      Images containing a dissection as a result of balloon angioplasty could not be
      analyzed by the automated system. The coefficient of variation between the lumen
      area measurements obtained with the automated system and the manual tracing
      system of images with a stent (n = 76) or stent graft (n = 79) was 2.7% and 2.1%,
      respectively. Correlation between the two systems was high (r = 1.00, p < 0.01)
      both for images containing stents or stent grafts. Minimum lumen area measured
      with the automated analysis system was smaller than minimum lumen area selected
      by visual estimation (mean difference 0.8 mm2 (4.9%) for stents and 2.4 mm2
      (10.9%) for stent grafts). The location of the smallest lumen area determined
      with both systems was the same (<1 cm) in 16 cases and differed more than 1 cm in
      4 other cases. CONCLUSIONS: The automated analysis system shows good agreement
      with manual contour analysis of lumen area in images with a stent or stent graft
      and is a reliable tool for determination of the smallest lumen area. The system
      is not able to analyze an irregular-shaped lumen area caused by a dissection.

PMID- 9546235
TI  - Human saphenous vein allograft bypass grafts: immune response.
AB  - Although it has been claimed that allografts of blood vessels might be successful
      because of minimal immunogenicity, they are subject to frequent and early
      failure, the cause of which has not been thoroughly investigated. We sought to
      define the immune response to allograft bypass. In a prospective trial, 40
      patients underwent cryopreserved venous allograft bypass. Allograft biopsies were
      performed at implantation and at allograft explantation in instances of graft
      failure. Tissues were evaluated in a blinded manner by means of standard
      histologic examination and paraffin immunohistochemical analysis with monoclonal
      antibodies against a variety of immune markers. During the 31-month follow-up
      period, 22 allografts were removed, and 19 were suitable for immunohistochemical
      study. Of these 19, 6 (32%) had moderate or severe infiltrates, which were evenly
      distributed throughout the intima, media, and adventitia. Immunohistochemical
      study of the explants demonstrated all of these infiltrates to be leukocytes
      (+LCA), which were predominantly activated T lymphocytes (+CD3, CD8, CR3)
      containing cytotoxic granules (+TIA-1). Macrophages were uncommon (+CD68); B
      cells (+L26, CD79) and natural killer cells (+CD56) were rare. Immunosuppression
      was associated with decreased presence of cytotoxic granules (TIA-1). Human
      venous allografts are immunogenic and prompt a T cell-mediated response.
      Allografts also fail without strong evidence of rejection, presumably because of
      local injury, hypercoagulability, or stasis. It may be possible to modify the
      contribution of rejection to venous allograft failure by means of
      immunosuppression and to modify the contribution of local hypercoagulability by
      means of anticoagulation.

PMID- 9546236
TI  - Genetic risk factor for abdominal aortic aneurysm: HLA-DR2(15), a Japanese study.
AB  - PURPOSE: Autoimmunity has been proposed to play a role in the pathogenesis of the
      abdominal aortic aneurysm (AAA). Several autoimmune diseases are associated with
      specific HLA DR alleles. These experiments were carried out to determine whether
      the same HLA DR types that have been reported to be associated with AAA in a
      mixed North American population are similarly associated with AAA in a more
      homogeneous group of patients in Japan. METHOD: HLA DR typing was performed by a
      serologic method on samples of peripheral blood of patients with nonspecific
      infrarenal AAA in Nagasaki University Hospital in Japan. The frequencies of HLA
      DR antigens were compared with those of volunteers approximately matched for age
      and sex from the same referral area. RESULTS: HLA DR haplotypes were determined
      in 46 Japanese patients with AAA and in 50 patients in a control group. The HLA
      DR2(15) antigen was observed in 27 (58.7%) patients (29 alleles 31.5%) with AAA
      and in 14 (28%) subjects (16 alleles 26.0%) in the control group (p < 0.005).
      CONCLUSIONS: The data suggest that HLA-DR2(15) has an important role as a genetic
      risk factor for AAA in Japanese patients, as previously reported in a mixed North
      American population.

PMID- 9546237
TI  - In vitro evaluation of electrostatic endothelial cell transplantation onto 4 mm
      interior diameter expanded polytetrafluoroethylene grafts.
AB  - PURPOSE: To perform an in vitro evaluation of electrostatic endothelial cell
      transplantation of human umbilical vein endothelial cells (HUVEC) onto segments
      of 4 mm internal diameter expanded polytetrafluoroethylene (ePTFE) vascular
      prostheses. METHODS: This evaluation consisted of exposing vascular graft
      segments that had been subjected to either electrostatic or gravitation
      transplantation with HUVEC to a physiologic shear stress (15 dynes/cm2) under
      steady flow conditions within a flow loop system. Biochemical assays were
      performed on freshly transplanted grafts by means of radioimmunoassay for
      prostacyclin and thromboxane A2. RESULTS: There was a 30% loss of HUVEC after 30
      minutes of shear stress exposure from the grafts subjected to gravitational
      transplantation with no additional significant (alpha = 0.05) loss after 120
      minutes. Grafts subjected to electrostatic transplantation had no significant
      (alpha = 0.05) loss of HUVEC during exposure to physiologic shear stress.
      Furthermore, after 120 minutes of shear-stress exposure, the grafts subjected to
      electrostatic transplantation (78,420 +/- 6274 HUVEC/cm2) retained 2.3 times more
      HUVEC than the counterparts subjected to gravitational transplantation (34,427 +/
      4637 HUVEC/cm2). The biochemical assay results indicated no significant (alpha =
      0.05) production of prostacyclin or thromboxane A2 regardless of the method of
      cell transplantation. CONCLUSIONS: (1) The electrostatic transplantation
      technique was superior to the gravitational transplantation technique in terms of
      cellular retention when the ePTFE grafts were exposed to physiologic shear
      stress. (2) Production of prostacyclin and thromboxane A2 did not differ between
      transplanted HUVEC subjected to gravitational or electrostatic procedures.

PMID- 9546238
TI  - Heparin inhibits thrombin-induced mitogen-activated protein kinase signaling in
      arterial smooth muscle cells.
AB  - PURPOSE: Smooth muscle cell proliferation is a key event in the development of
      intimal hyperplasia after arterial injury. Heparin can suppress smooth muscle
      cell proliferation in vitro and prevents intimal hyperplasia after arterial
      injury, but the mechanisms of action are poorly understood. Recently, we observed
      that heparin inhibited serum-induced activation of mitogen-activated protein
      kinase in smooth muscle cells, but heparin did not inhibit signaling induced by
      platelet-derived growth factor BB and basic fibroblast growth factor, both
      ligands of tyrosine kinase receptors. Here, we examined the possibility that
      heparin inhibits signaling by thrombin and other activators of heterotrimeric G
      proteins. DESIGN OF STUDY: Baboon aortic smooth muscle cells were stimulated with
      thrombin, angiotensin II, endothelin-1, and lysophosphatidic acid in the presence
      or absence of heparin. After stimulation, mitogen-activated protein kinase
      activity was measured with an in-gel phosphorylation assay, mitogen-activated
      protein kinase kinase-1 was immunoprecipitated from the same samples, and
      activity was measured with recombinant mitogen-activated protein kinase as a
      substrate. DNA synthesis was measured by 3H-thymidine labeling and scintillation
      counting. RESULTS: Heparin inhibited sustained activity of mitogen-activated
      protein kinase kinase-1 and mitogen-activated protein kinase and prevented DNA
      synthesis induced by thrombin, angiotensin II, endothelin-1, and lysophosphatidic
      acid. CONCLUSIONS: Heparin inhibits growth of baboon smooth muscle cells by
      preventing prolonged mitogen-activated protein kinase activation elicited by
      ligands of seven transmembrane domain receptors and heterotrimeric G-proteins.
      The results indicate that heparin interferes with a specific pathway in smooth
      muscle cell growth, which could be a future target in attempts to inhibit lesion
      development after vascular surgery.

PMID- 9546239
TI  - Enhancement of tissue factor expression by vein segments exposed to coronary
      arterial hemodynamics.
AB  - PURPOSE: Although saphenous vein is the most reliable conduit for arterial
      interposition procedures in the coronary circulation, graft thrombosis remains a
      clinical problem. We hypothesized that an important factor in early graft
      thrombosis is sudden change in the hemodynamic environment of the vein as it is
      placed in the coronary circulation. METHODS: We used an ex vivo perfusion system
      to study freshly excised segments of human saphenous vein (HSV) and pig internal
      jugular vein. For coronary graft (CAVG) simulation, sections of HSV were
      subjected to arterial pulsatile pressure and flow and twisting and stretching to
      mimic deformations caused by the beating heart. Using functional and
      immunohistochemical assays, we investigated the effect of these conditions on
      expression of tissue factor (TF), an important prothrombotic surface molecule.
      RESULTS: In each of 11 experiments (6 human, 5 porcine), vein segments from a
      single donor were subjected to venous conditions (VEN), CAVG perfusion, or no
      perfusion. Expression of TF was measured as the amount of factor Xa generated per
      unit area of luminal vein surface. VEN perfusion did not cause a significant
      change in mean TF expression over nonperfused control values (human: 14.3 +/- 1.5
      versus 11.4 +/- 2.3 U/cm2, p = 0.31; pig: 11.6 +/- 1.5 versus 12.5 +/- 1.4 U/cm2,
      p = 0.70). CAVG perfusion led to significant enhancement of TF expression over
      VEN perfusion (human: 36.8 +/- 6.2 versus 14.3 +/- 1.5 U/cm2, p < 0.05; pig: 40.0
      +/- 9.9 versus 11.6 +/- 1.5 U/cm2, p < 0.05). Immunohistochemical analysis showed
      positive TF staining on the luminal side of a CAVG-stimulated HSV segment, but
      not on a VEN-stimulated segment. In four additional studies, HSV segments were
      subjected to arterial perfusion without twist and stretch to mimic lower
      extremity arterial interposition grafts. TF expression for lower extremity venous
      graft perfusion was significantly higher than for VEN perfusion (25.3 +/- 2.5
      versus 14.3 +/- 1.5, p < 0.01) but not significantly different from CAVG
      perfusion. CONCLUSIONS: Our studies in a unique perfusion system suggest that
      exposure of vein to coronary arterial hemodynamic conditions results in elevated
      expression of the important prothrombotic molecule TF. This phenomenon may
      contribute to early graft thrombosis.

PMID- 9546240
TI  - Functional activity and transmembrane signaling mechanisms after cryopreservation
      of human internal mammary arteries.
AB  - PURPOSE: Cryopreserved human blood vessels are important tools in bypass surgery.
      However, several in vitro studies have demonstrated diminished postthaw
      functional activity. Therefore the aim of this study was to investigate the
      consequences of various freezing/thawing protocols and the role of protein kinase
      C in the postthaw functional activity of cryopreserved human arteries. METHODS:
      In vitro responses of frozen/thawed human internal mammary arteries (IMA) were
      used to investigate the functional activity after thawing at 15 degrees, 30
      degrees, and 100 degrees C/min and after different prefreezing equilibration
      times (10, 60, 120, 240 minutes) with the cryomedium (Krebs-Henseleit solution
      containing 1.8 mol/L dimethyl sulfoxide and 0.1 mol/L sucrose) at room
      temperature followed by cryostorage at -196 degrees C. RESULTS: Prefreezing
      equilibration for 10 to 120 minutes diminished maximal alpha-adrenoceptor
      mediated responses to noradrenaline to approximately 60%, and equilibration for
      240 minutes attenuated noradrenaline effects to less than 25% of that produced by
      unfrozen controls. Contractile responses were slightly better when thawing was
      performed at 15 degrees C/min compared with 100 degrees C/min. The postthaw
      sensitivity to direct activation of protein kinase C by phorbol 12,13-dibutyrate
      was enhanced. Compared with unfrozen tissues (pD2 = 7.36 +/- 0.07, n = 32)
      maximal sensitization to phorbol 12,13-dibutyrate was observed in IMA that had
      been frozen after 60 minutes of equilibration with the cryomedium (pD2 = 8.31 +/-
      0.09, n = 30). Responses to phorbol 12,13-dibutyrate of cryopreserved IMA were
      highly susceptible to blockade of calcium influx by nifedipine, whereas those of
      unfrozen IMA were resistant to nifedipine. Against noradrenaline nifedipine was
      equipotent in cryopreserved (pD'2 = 7.75 +/- 0.15, n = 8) and unfrozen IMA (pD'2
      = 7.70 +/- 0.10, n = 6). Endothelium-dependent relaxant responses to
      acetylcholine were significantly attenuated after cryopreservation (Emax = 26% +/
      5%, n = 4) compared with unfrozen IMA (Emax = 71% +/- 4%, n = 4, p < 0.001);
      endothelium-independent relaxant responses to sodium nitroprusside were
      unchanged. CONCLUSIONS: Cryopreservation of human IMA under the conditions
      applied in this study (1) attenuated endothelial cell function and (2) induced an
      activation of protein kinase C, thereby increasing calcium influx through
      dihydropyridine-sensitive calcium channels. These experimental data suggest that
      postoperative administration of calcium channel blockers alone or combined with
      long-acting nitrates should effectively prevent the development of spasms in
      arterial grafts.

PMID- 9546241
TI  - Acute traumatic rupture of the thoracic aorta: delayed treatment with endoluminal
      covered stent. A report of two cases.

PMID- 9546242
TI  - Iliac and femoral artery occlusion by thromboemboli from an abdominal aortic
      aneurysm in the setting of blunt abdominal trauma.
AB  - The abdominal aorta is injured infrequently in blunt trauma to the abdomen. When
      injury does occur, aortic rupture, dissection, and traumatic aneurysm most
      commonly result. An aneurysmal abdominal aorta would appear to be at increased
      risk for injury from blunt abdominal trauma. This case report appears to be the
      first description of iliac and femoral artery occlusion by thromboemboli
      dislodged from an atherosclerotic abdominal aortic aneurysm at the time of a
      motor vehicle accident. We believe that this peripheral embolization was caused
      by direct compression of the abdominal aortic aneurysm by a seatbelt.

PMID- 9546243
TI  - Subclavian artery pseudoaneurysm in type IV Ehlers-Danlos syndrome.
AB  - We report case of a subclavian artery pseudoaneurysm in a patient with type IV
      Ehlers-Danlos Syndrome. A 16-year-old boy underwent successful repair of a
      subclavian artery pseudoaneurysm that occurred after a cervical hyperextension
      injury. Subsequent workup included skin biopsy and fibroblast culture, which were
      consistent with a diagnosis of type IV Ehlers-Danlos Syndrome. This condition is
      a dominantly inherited connective tissue disorder, which in this patient was
      found to be caused by a spontaneous point mutation in the COL3A1 gene that
      encodes the chains of type III procollagen. The clinical, genetic, and molecular
      characteristics of type IV Ehlers-Danlos Syndrome are briefly reviewed.

PMID- 9546244
TI  - Successful delayed bilateral renal revascularization during active phase of
      Takayasu's arteritis.
AB  - Successful bilateral renal revascularization was performed 24 days after the
      development of angiotensin converting enzyme-inhibitor-induced bilateral renal
      artery thrombosis and anuric acute renal failure in a patient with Takayasu's
      arteritis. Excellent results were obtained after an unusually long ischemic time
      for a patient with active-phase disease. The outcome suggests that aggressive
      surgical revascularization can benefit patients with renal failure caused by
      renal arterial occlusion during the active phase of Takayasu's arteritis.

PMID- 9546245
TI  - Primary aortic intimal sarcoma of the endothelial cell type with long-term
      survival.
AB  - Primary tumors of the aorta are rare and are difficult to diagnose
      preoperatively. These tumors are malignant and ultimately fatal. A patient had
      initial evidence of aortoiliac obstructive disease. Aortic endarterectomy
      produced an excellent postoperative clinical result until the pathology report
      from the endarterectomy specimen revealed aortic sarcoma. The patient refused a
      second operation for en bloc aortic resection. One year later with recurrent
      symptoms, the patient underwent en bloc resection of the aorta and common iliac
      vessels until clear margins were obtained. The tumor was found to be intimal
      aortic sarcoma of endothelial cell origin. The only metastasis was to bone, and
      it was controlled with radiation and chemotherapy. The patient lived a total of 8
      years from the time of initial diagnosis. Abdominal aortic intimal sarcoma of the
      endothelial cell type is a rare variety of aortic sarcoma that can be managed
      successfully if diagnosed early. This specific type of tumor has a longer
      survival period and better prognosis than other types of aortic sarcoma when
      managed with aggressive surgical resection, radiation, and chemotherapy.

PMID- 9546246
TI  - Superior mesenteric arterial occlusion from a leiomyoma.
AB  - We report a solitary leiomyoma of the superior mesenteric artery resulting in
      arterial occlusion and gangrenous bowel. On histologic evaluation the lesion
      extended into the vessel lumen off its stalk and showed immunostaining for smooth
      muscle antigen and desmin. Leiomyomas can arise anywhere there is smooth muscle
      and occur most commonly in the uterus followed by the skin and gastrointestinal
      tract. We could not identify any previous case in the literature of a leiomyoma
      arising from within the wall of a mesenteric vessel.

PMID- 9546247
TI  - Spontaneous tibial artery thrombosis associated with varicella pneumonia and free
      protein S deficiency.
AB  - Pneumonia is the most common serious complication of varicella infection in
      adults. A variety of thrombotic complications including purpura fulminans and
      disseminated intravascular coagulation have been reported in children with
      varicella but not in adults. Two men with varicella pneumonia who had profound
      lower extremity ischemia caused by thrombosis of the profunda femoris and tibial
      arteries are reported. Both patients had free protein S deficiency and vascular
      thrombosis in association with varicella pneumonia without overt evidence of
      disseminated intravascular coagulation or purpura fulminans. Antiphospholipid
      immunoglobulin G and immunoglobulin M antibodies were present in one, whereas the
      other had evidence of the lupus anticoagulant. The proposed pathogenesis and
      management options including intraarterial thrombolytic therapy with urokinase
      and the need for long-term anticoagulation are discussed.

PMID- 9546248
TI  - Intraoperative monitoring of danaparoid sodium anticoagulation during
      cardiovascular operations.
AB  - PURPOSE: Patients with cardiovascular disorders frequently need anticoagulation
      for diagnostic studies, surgical procedures, and therapy. Heparin-induced
      thrombocytopenia is a relatively common complication of heparin therapy that can
      result in thrombosis and subsequent limb loss or death, necessitating use of
      alternative anticoagulants. METHODS: Two patients who needed cardiac surgery had
      thrombocytopenia induced by exposure to heparin and heparin-coated tubing.
      Several assays were examined for their ability to monitor intraoperative
      anticoagulation of a factor Xa inhibitor, danaparoid sodium. RESULTS: In vitro,
      celite and kaolin activated dotting times and activated partial thromboplastin
      time were prolonged linearly in the presence of increasing concentrations of
      danaparoid sodium. Aprotinin did not alter the linearity of the response but did
      alter its slope. In vivo, activated clotting times and activated partial
      thromboplastin time were insensitive to clinically significant changes in
      danaparoid sodium plasma levels during cardiopulmonary bypass. Correction in
      activated partial thromboplastin time lagged 2 hours behind clinically important
      changes in anti-factor Xa levels. Only anti-factor Xa levels were adequate to
      monitor intraoperative danaparoid sodium levels. CONCLUSION: Anticoagulation for
      cardiopulmonary bypass can be successfully performed with danaparoid sodium and
      intraoperative anti-factor Xa monitoring.

PMID- 9546249
TI  - A new surgical approach to the innominate and subclavian vein.
AB  - A new technique extending the incision used for thoracic outlet decompression
      with a subclavicular approach to the first rib is presented. After the first rib
      and scalenotomy are removed, the subclavicular incision is continued into the
      sternum medially and superiorly to the sternal notch. This gives easy access to
      the innominate-subclavian-axillary vein segment. Eight patients with extensive
      chronic fibrotic obstruction of the subclavian-innominate vein segment underwent
      operation with this technique. It allows placement of either long patches of
      saphenous vein to reestablish normal caliber or replacement, as is our choice,
      with a small-sized cryopreserved descending thoracic aortic homograft. The
      operation is carried out in an extrapleural plane preserving the sternoclavicular
      joint, avoiding the deformity caused by transclavicular techniques. Repair of the
      sternotomy creates a stable incision. Follow-up to 14 months shows patency of the
      venous channel with no complications. This surgical approach is recommended to
      solve the problem of satisfactory exposure of the subclavian-innominate venous
      channel after decompression of the thoracic outlet.

PMID- 9546250
TI  - Technique for obtaining proximal intraluminal control when arteries are
      inaccessible or unclampable because of disease or calcification.
AB  - When proximal arterial control cannot be obtained by standard methods, it may be
      achieved safely and bloodlessly by intraluminal routes with balloon catheters,
      hemostatic sheaths, and catheter-guide wire techniques. This method was used
      successfully in 20 patients to achieve proximal arterial control without
      complications in a variety of locations. Use of this method or its modifications
      may facilitate and simplify a variety of vascular operations that would otherwise
      be difficult or hazardous.

PMID- 9546251
TI  - Regarding "Detection of active cytomegalovirus infection in inflammatory aortic
      aneurysms with RNA polymerase chain reaction".

PMID- 9546252
TI  - Use of an internal saphenous varicose vein covered by a polytetrafluoroethylene
      prosthesis in a femoropopliteal bypass graft.

PMID- 9546253
TI  - Ultrasound-guided interstitial Nd: YAG laser treatment of voluminous hemangiomas
      and vascular malformations in 92 patients.
AB  - In many cases voluminous vascular anomalies of the head and neck region are still
      treated with conventional surgery, although neodymium:yttrium-aluminum-garnet
      (Nd:YAG) laser therapy offers a valuable treatment alternative. Ninety-two
      patients with voluminous hemangiomas and vascular malformations were treated with
      interstitial Nd:YAG laser therapy (power density, 1300 to 3300 W/cm2), partly
      complemented by a noncontact-mode Nd:YAG laser light application (energy density,
      1000 to 2500 J/cm2). The vascular tumors had a diameter of more than 3 cm in at
      least two dimensions. Treatment was carried out under ultrasound and manual
      control. Nearly 60% of the patients (n = 55) showed a complete clinical
      regression. Thirty-three patients (35.8%) had a partial regression and were
      satisfied with the treatment outcome. Four patients were treated unsuccessfully
      with the laser, and three of them subsequently underwent conventional surgery.
      Only nine of the 92 patients (9.8%) showed cosmetic or functional impairments.
      The results of this first consecutive series study with a retrospective clinical
      evaluation of the interstitial Nd:YAG laser therapy of voluminous hemangiomas and
      vascular malformations in a large patient group demonstrate a high effectiveness
      of this novel therapy modality.

PMID- 9546254
TI  - Diagnosis of head and neck precancerous lesions in an animal model using
      fluorescence spectroscopy.
AB  - Laser-induced fluorescence (LIF) of tissues depends on their biochemical and
      histomorphologic characteristics. LIF spectroscopic properties of 9,10-dimethyl
      1,2-benzanthracene (DMBA)-induced precancerous and early cancerous lesions in a
      hamster buccal pouch mucosa model were studied. Fluorescence spectra from
      neoplastic lesions showed a characteristic fluorescence peak in the red region of
      the visible spectrum centered between 630 and 640 nm when excited with 410-nm
      light. Using this as a diagnostic criterion, 45 of 49 lesions studied were
      correctly diagnosed, including early dysplastic lesions. Follow-up study of four
      dysplastic lesions over 2 weeks revealed an increase in red fluorescence
      intensity. The findings of these experiments suggest that LIF spectroscopy may be
      a valuable noninvasive technique not only for early diagnosis of head and neck
      cancer, but also to probe a possible biochemical surrogate biomarker in the
      follow-up of suspected lesions.

PMID- 9546255
TI  - Reconstruction after temporal bone resection.
AB  - Reconstruction of soft tissue defects after temporal bone resection can vary from
      simple closure of the external auditory canal to complex flap coverage of
      extensive defects. Between 1987 and 1996, 34 patients underwent lateral skull
      base resections and reconstruction for invasive carcinoma of the temporal bone.
      Seven underwent sleeve resection and/or radical mastoidectomy. Sleeve resection
      was managed with tympanoplasty, canalplasty, or obliteration of the external
      auditory canal (10). There were 24 lateral temporal bone resections and four
      subtotal temporal bone resections. Larger defects created by lateral and subtotal
      temporal bone resections required closure with a combination of temporalis flaps
      and local rotational cutaneous flaps (13). Lower island trapezius flaps (five),
      free flaps (four), and pectoralis major flaps (two) were also used. Indications
      and efficacy of each method are discussed, and treatment outcomes are presented.

PMID- 9546256
TI  - Combining free flap reconstruction and craniofacial prosthetic technique for
      orbit, scalp, and temporal defects.
AB  - OBJECTIVES: To identify factors leading to successful application of prosthetic
      techniques following free flap reconstruction of the orbit, scalp, and temporal
      region. STUDY DESIGN: Retrospective review. METHODS: Twenty-eight patients who
      underwent free flap reconstruction for defects of these regions between 1989 and
      1996 were reviewed for clinical parameters, flap loss, patient survival, and
      implant loss rate. Prosthetic usage rates were compared before and after
      introduction of a site-specific reconstructive algorithm. RESULTS: Free flap
      success rate was 93%, whereas osseointegrated implant loss rate was 11%. In
      addition to implants, a reconstructive strategy that provided thin, vascular
      tissue between bone and skin, a flat platform in the temporal region, and
      preservation of orbital cavity depth led to increased prosthetic usage.
      CONCLUSIONS: Craniofacial prosthetic techniques can significantly augment the
      results of free flap surgery for the orbit, scalp, and temporal region.
      Successful combination of these techniques requires a site-specific surgical
      approach.

PMID- 9546257
TI  - Interactive magnetic resonance imaging-guided biopsy in the head and neck:
      initial patient experience.
AB  - Because of its excellent soft tissue resolution, magnetic resonance imaging (MRI)
      can optimize image guidance for interventional and surgical procedures. Notably,
      needle biopsy of head and neck lesions has been used for years, deeper lesions
      often requiring some form of image guidance. The closed space of diagnostic MRI
      scanners proves cumbersome for intervention. The authors report on the first head
      and neck image-guided biopsies performed in a new, investigational "open
      configuration" intraoperative MRI scanner. Vertical space between the scanner's
      upright coils gives access to the patient while imaging; image acquisition is as
      fast as 2 sec/image. Biopsies were performed on seven patients (parotid,
      parapharyngeal space, second cervical vertebra); five specimens were diagnostic.
      Both general anesthesia and intravenous sedation were used. The procedures were
      without complications. Imaging provided definition of anatomy to direct needle
      placement. Access to the patient allowed for both percutaneous and transoral
      approaches. The environment of the open magnet is well suited for biopsy of the
      head and neck, and near real-time intraoperative MRI has promise for guiding more
      complex head and neck procedures. Further study should optimize the quality of
      the images and the interactibility of localization and targeting and fully
      utilize MRI's three-dimensional imaging capabilities.

PMID- 9546258
TI  - Relative accuracy of fine-needle aspiration and frozen section in the diagnosis
      of well-differentiated thyroid cancer.
AB  - The need for and extent of thyroid surgery for a thyroid nodule is usually
      primarily based on fine-needle aspiration (FNA) and frozen section diagnosis. The
      relative role of these modalities in 66 patients who had undergone FNA and
      subsequent thyroidectomy with frozen section was investigated. Cases that
      demonstrated discordance between FNA and frozen section (n = 22; 33%) were
      identified, and all slides were re-reviewed by a cytopathologist using current
      established cytologic criteria. A change in diagnosis was made in 13 cases with
      an increase in accuracy of FNA from 71% to 88%. The accuracy of frozen section
      (92%) did not change appreciably with re-review (94%). The accuracy of FNA and
      frozen section combined was found to be 98%. The rate of discordance decreased
      from 33% to 13% with re-review. When strict histologic and cytologic criteria are
      applied, FNA and frozen section are accurate and complementary methods that help
      in determining the operative management of thyroid masses. However, when FNA
      yields a diagnosis of "follicular neoplasm," frozen section is unlikely to change
      this diagnosis.

PMID- 9546259
TI  - Identification of p53 and human papilloma virus in Schneiderian papillomas.
AB  - Schneiderian papilloma of the nose is an unusual neoplasm with the propensity for
      local tissue destruction, recurrence, and malignant degeneration. Human papilloma
      virus (HPV) is related to a subset of sinonasal papillomas and has been
      implicated in the pathogenesis of cancer by interaction with the host p53
      protein. Detection of p53 and HPV could be clinically useful as tumor markers for
      lesions with oncogenic potential. Thirty specimens for p53 were studied and nine
      (30%) stained positive. HPV was detected in six (20%). In the presence of p53, an
      odds ratio for carcinoma was 1.19:1, or 19% higher than expected. In the presence
      of HPV the odds ratio for carcinoma was 11.5:1, or 11.5 times higher than
      expected. In the presence of HPV an odds ratio for finding an elevated amount of
      p53 was 2.2:1. The data support the hypothesis that HPV and p53 may interact in a
      novel manner and elevate the risk for neoplasia.

PMID- 9546261
TI  - Identification of obstructive sleep apnea in patients who snore.
AB  - As the field of sleep medicine has evolved, the clinical implications of
      obstructive sleep apnea (OSA) in snoring patients have become well accepted.
      Recent advances in surgical therapy for snoring allow otolaryngologists to offer
      simple outpatient treatment to patients with this problem. However, because the
      incidence of OSA in snorers seeking medical attention is unknown, the appropriate
      pretreatment evaluation of these patients is a subject of continued debate.
      Ninety-four snoring patients were recruited for a study to determine the
      incidence of OSA in this highly selected population. Subjects answered an
      extensive sleep questionnaire to determine factors that might suggest a diagnosis
      of OSA. Level III ambulatory sleep studies were performed on each participant.
      The incidence of OSA in this group was 72% (42% severe and 30% mild to moderate).
      Twenty of the subjects with OSA also underwent formal level I sleep studies, and
      the diagnosis of OSA was confirmed in each instance. Although there was a
      relationship between body mass index and OSA and certain questions correlated
      with OSA, the sensitivity and specificity of these data alone or in combination
      were too low to recommend their use in lieu of a formal sleep study. Given the
      remarkably high incidence of OSA in this group, which may reflect that seen by
      otolaryngologists who treat snoring, a sleep study should be performed to
      diagnose OSA and institute therapy for this condition. Level III ambulatory
      monitoring devices may be the most cost-effective alternative for evaluating this
      high-risk population.

PMID- 9546260
TI  - Histology and histomorphometry of ethmoid bone in chronic rhinosinusitis.
AB  - Mucosal changes have been well described in chronic sinusitis, yet little is
      known about the underlying bone, despite clinical and experimental evidence
      suggesting that bone may be involved in chronic sinusitis. Techniques of
      undecalcified bone analysis were used for detailed histologic examination of
      ethmoid bone in chronic sinusitis compared with controls. Bone synthesis,
      resorption, and inflammatory cell presence were specifically assessed.
      Additionally, histomorphometry techniques were used to determine ethmoid bone
      physiology in individuals undergoing surgery for chronic sinusitis. Overall,
      individuals undergoing surgery for chronic sinusitis were found to have evidence
      of marked acceleration in bone physiology with histologic changes including new
      bone formation, fibrosis, and presence of inflammatory cells. These findings are
      compared with osteomyelitis in long bone and the jaw. The suggestion that
      underlying bone may serve as a catalyst for chronic sinusitis is supported and
      implications for therapy are discussed.

PMID- 9546262
TI  - Influence of size and etiology of glottal gap in glottic incompetence dysphonia.
AB  - This study investigates the relationship between glottal gap and vocal function
      in patients with glottic incompetence dysphonia. Twenty patients with vocal fold
      paralysis (VFP), 17 patients with vocal fold atrophy (VFA), and five patients
      with sulcus vocalis (SV) were examined. Glottal gap area at the most closed point
      of vibration was measured using digitized videostroboscopic images. Glottal gap
      area was correlated with acoustic and aerodynamic measures of vocal function.
      Patients with VFP had the largest glottal gaps and had significantly worse vocal
      function than did the patients with VFA or SV. Regardless of groups, however,
      where glottal gap size was similar, there was no difference in vocal function.
      Therefore vocal function was mainly influenced by glottal gap size, not by
      whether glottic incompetence was the result of VFP, VFA, or SV.

PMID- 9546264
TI  - Lipoperoxidation as a measure of free radical injury in otitis media.
AB  - Free radical damage, as evidenced by lipoperoxidation, has previously been
      demonstrated to contribute to the inflammatory changes associated with acute
      otitis media. The present study was undertaken to evaluate whether
      lipoperoxidation continues to be present for a period of time after middle ear
      infection. Eighty-two 300- to 400-g guinea pigs were injected with Streptococcus
      pneumoniae in the left ear and sterile saline in the right ear as a control.
      Animals were examined and sacrificed on day 5, 10, 20, or 30; middle ear mucosa
      was harvested and assayed for lipid hydroperoxide content. A statistically
      significant increase in lipoperoxidation was seen at each time point studied,
      compared with controls. Lipoperoxidation was highest at days 5 and 10; a
      significant decrease was seen at days 20 and 30. Histologic sections of middle
      ear mucosa of two animals per group were prepared and evaluated for inflammation.
      These results demonstrate that lipoperoxidation may contribute to middle ear
      inflammation for a significant period of time after acute infection; the findings
      are discussed in light of other work on the role of free radicals in otitis
      media.

PMID- 9546263
TI  - Pediatric bilateral facial paralysis.
AB  - Bilateral facial paralysis is an unusual clinical entity that occurs in less than
      1% of patients with facial paralysis. In children bilateral facial paralysis is
      even more rare, and establishing its etiology can be challenging. Four pediatric
      patients ranging in age from 3 to 17 years are presented who developed bilateral
      facial paralysis as a result of acute otitis media, Lyme disease, recurrent
      central nervous system leukemia, and acute disseminated encephalomyelitis. The
      diagnosis and treatment of pediatric bilateral facial paralysis are reviewed, as
      well as the pertinent literature.

PMID- 9546265
TI  - Hearing results with the Dornhoffer ossicular replacement prostheses.
AB  - The "ideal" prosthesis for ossicular reconstruction should, from a surgical
      standpoint, require easy manipulation, reduce surgeries to partial or total
      variants, and be constructed of stable, biocompatible material. From an acoustic
      standpoint, a prosthesis should weigh 10 to 40 mg, provide proper tension between
      the tympanic membrane (TM) and stapes, form less than a 30-degree angle with the
      TM, and accommodate the malleus. Work was conducted with Smith & Nephew Richards,
      Inc. (Memphis, TN), to develop a partial ossicular replacement prosthesis (PORP)
      and a total ossicular replacement prosthesis (TORP) that combined the majority of
      these features. This retrospective study used a computerized otologic database to
      identify patients implanted with a Dornhoffer HAPEX PORP or TORP from June 1995
      to March 1997. The surgical procedures utilizing these prostheses were primary
      cholesteatoma and revision surgery of previously performed modified or radical
      mastoidectomies complicated by poor hearing or chronically draining cavities.
      Preoperative and postoperative air and bone conduction four-frequency (500, 1000,
      2000, and 3000 Hz) pure-tone averages (PTAs) were used to calculate the PTA air
      bone gaps (ABGs). Results in 52 cases (follow-up, 1 year) showed a statistically
      significant improvement in hearing (P < 0.05) for each group. Excellent hearing
      results (< or = 10 dB PTA-ABG) were seen in 69% of PORP cases and in 35% of TORP
      cases, and good results (11 to 20 dB PTA-ABG) were seen in 31% and 50% of PORP
      and TORP cases, respectively. Designing an ossicular replacement prosthesis with
      both surgical and acoustic factors in mind has led to encouraging short-term
      hearing results.

PMID- 9546266
TI  - A study on epidermal proliferation ability in cholesteatoma.
AB  - With the objective of estimating proliferation ability of epidermis of middle ear
      cholesteatoma, the difference in proliferating cell nuclear antigen (PCNA)
      staining between the skin of the bone region of the external ear canal (control
      skin) and cholesteatoma epidermis and the effects on PCNA staining of
      subepidermal inflammatory cell infiltration of cholesteatoma were
      immunohistochemically studied using an antibody against PCNA. Transforming growth
      factor-alpha (TGF-alpha) is known to promote epidermal proliferation based on
      autocrine mechanism. But it is not clear that cholesteatoma epidermis is actually
      in the state of hyperproliferation under the effect of this growth factor. To
      estimate the effect of TGF-alpha on epidermal proliferation ability, the authors
      compared the location of PCNA and TGF-alpha in the same specimen. Unlike the
      control skin, not only epidermal basal cell layer and suprabasal cell layer, but
      also more superior layers were found to have high levels of PCNA staining in the
      epidermis of cholesteatoma. However, in the same cholesteatoma epidermal tissue,
      the PCNA staining was varied and the difference was ascribable to subepidermal
      cell inflammation. It appeared that the proliferation ability was high in regions
      where subepidermal inflammatory cell infiltration was severe. These differences
      in microenvironment are inferred to greatly affect proliferation ability of
      cholesteatoma epidermis.

PMID- 9546268
TI  - Audiometric results of bilateral bone-anchored hearing aid application in
      patients with bilateral congenital aural atresia.
AB  - The effect of bilateral application of bone-anchored hearing aids (BAHAs) was
      examined in terms of directional hearing and speech recognition in quiet and in
      noise in four patients with bilateral congenital atresia who, out of pure
      necessity, had been using a unilateral bone-conduction hearing aid since early
      life. This study comprised a prospective clinical evaluation in a single subject
      design; four patients with bilateral congenital atresia originating from the
      Nijmegen BAHA series participated. Three patients had Treacher Collins syndrome.
      All four patients had conductive, most probably, symmetrical, hearing loss.
      Recently these patients had applied for a second BAHA and were subsequently
      fitted bilaterally. With two BAHAs, all four patients showed significant
      improvement in sound localization. Also, speech perception in quiet showed
      significant improvement with bilateral application, and a significant improvement
      was found in speech perception in noise in three patients. These results suggest
      that patients with congenital conductive, symmetrical hearing loss will benefit
      from bilateral BAHAs.

PMID- 9546267
TI  - Effect of intratympanic steroid application on the development of experimental
      cholesteatoma.
AB  - By introducing certain irritants into the middle ear it is possible to produce
      cholesteatoma. Propylene glycol, the main agent used for this purpose, produces a
      long-standing inflammation that causes hyperplasia and migration of the
      epithelium through an intact tympanic membrane. In the present investigation
      topical prednisolone was used in order to inhibit the production of
      cholesteatoma. The results indicate that there is a marked decrease in
      inflammation and hence experimental cholesteatoma production when prednisolone is
      administered into the middle ear.

PMID- 9546269
TI  - Correlation between electrical auditory brainstem response and perceptual
      thresholds in Digisonic cochlear implant users.
AB  - OBJECTIVES: To examine the relationships between psychophysical perceptions and
      the electrically evoked auditory brainstem responses (EABRs) in multichannel
      cochlear implant (CI) users and to determine the effectiveness of EABRs in
      electrode failure. DESIGN: A descriptive study reported the EABR characteristics
      while the different electrodes were activated. Characteristics of the EABR and of
      the perceptual measures served as compared variables in a correlational study.
      SETTING: The study was carried out in the audiology clinic of an otolaryngology
      department at a university hospital. PATIENTS: The subjects consisted of nine
      consecutively selected habitual Digisonic DX1OR multichannel CI users. Seven
      patients were postlinguistically deafened adult patients; two were congenitally
      deaf children. MAIN OUTCOME MEASURES: Ipsilateral recordings were performed using
      a previously published method. Morphology, latency, and amplitude measures of the
      EABR recordings were described, computed, and compared with the literature data
      for EABRs obtained while activating other types of CI and for acoustically evoked
      ABRs. Correlations between EABRs and behavioral perception thresholds were
      analyzed using the parametric Pearson's correlation test. RESULTS: EABRs allowed
      the authors to detect failure of no. 10 electrode integrity in one child.
      Perceptual threshold measures were found to be highly significantly related to
      the EABR threshold across subjects and electrode position (n = 31, r = 0.98; P <
      0.001; linear regression equation: perceptual threshold = 1.06 EABR threshold +
      0.76). The latencies and amplitudes were found to be similar to those described
      in the literature. CONCLUSIONS: EABRs may be used to estimate settings for the
      Digisonic DX10 CI even in a pediatric population, although they cannot entirely
      replace behavioral measurements, especially in children. The EABR can be employed
      for electrode dysfunction diagnosis. Further studies are needed to determine
      whether recordings of EABR quality could contribute to the evaluation of
      functional prognosis during the rehabilitation.

PMID- 9546270
TI  - Optimization of speech processor fitting strategies for Chinese-speaking cochlear
      implantees.
AB  - OBJECTIVES: To compare speech recognition performance in Chinese-speaking
      cochlear implant patients with a speech processor program selected by the
      clinical audiologist in Taiwan and with a new speech processor program based on
      the Washington University clinical procedure developed by Skinner et al. STUDY
      DESIGN: Six adult Chinese-speaking patients implanted with the Nucleus cochlear
      implant system participated in this study. METHODS: A fitting procedure developed
      in 1995 by Skinner et al. at Washington University School of Medicine was used to
      create a new speech processor program to optimize each patient's hearing in
      everyday life. Speech tests (vowels, consonants, tones, and words), sound-field
      thresholds, and a self-report questionnaire were used to evaluate each patient's
      performance with his or her previous speech processor program and a new one.
      RESULTS: Four of the six patients had significant changes from the previous to
      the new speech processor program. These changes were associated with improvement
      in score on at least one speech test, more sensitive sound field thresholds, and
      reported improvement in some everyday listening situations on the questionnaire.
      CONCLUSIONS: These results suggest that use of this procedure with adult cochlear
      implantees may improve benefit in everyday life. Analysis of the speech test
      stimuli and patients' responses provides a basis for modification or creation of
      new Mandarin Chinese speech tests for preoperative and postoperative evaluation
      of adult cochlear implant patients.

PMID- 9546271
TI  - Short- and long-term results of stapedectomy in children.
AB  - Studies have indicated that stapedectomy can be an effective procedure in
      children for correcting conductive hearing losses due to juvenile otosclerosis.
      However, because childhood otosclerosis is rare and children commonly choose to
      use hearing aids in lieu of undergoing surgery, little outcome data are
      available. The purpose of this retrospective study was to provide additional
      outcome data in both the short and the long term. Stapedectomies were performed
      on 47 children. Preoperative hearing results were compared with 6-month
      postoperative hearing results. Hearing results for the children who had long-term
      follow-up (5 years or more) were compared with the 6-month postoperative results.
      Stapedectomy was successful (postoperative air conduction pure-tone average [PTA]
      within 10 dB of the preoperative bone conduction PTA) in 91.7% of the cases. The
      mean overclosure of the preoperative bone conduction PTA by the postoperative air
      conduction PTA was 0.2 dB. The mean PTA hearing improvement was 32.8 dB. Results
      from the 21 children (28 ears) who had long-term follow-up indicated an average
      0.7 dB/year PTA worsening from the 6-month postoperative PTA. Results from this
      study provide additional evidence that stapedectomy can be an effective procedure
      for correcting conductive hearing losses due to juvenile otosclerosis.

PMID- 9546272
TI  - Idiopathic facial paralysis: a randomized, prospective, and controlled study
      using single-dose prednisone versus acyclovir three times daily.
AB  - In a prospective, controlled, and randomized study, we compared the outcome of
      101 Bell's palsy patients treated with acyclovir (54 patients) or prednisone (47
      patients). The acyclovir dosage was 2400 mg (800 mg three times a day) for 10
      days, and prednisone was given as a single daily dose of 1 mg/kg of body weight
      for 10 days and tapered to 0 over the next 6 days. Minimum follow-up was 3 months
      in all patients. Patients in the prednisone group had better clinical recovery
      than those treated with acyclovir. Less degree of neural degeneration was
      observed in the prednisone group compared with acyclovir patients. The incidence
      of sequelae was the same in both groups. According to these results, in a 10-day
      treatment cycle acyclovir given 800 mg three times is not as useful as prednisone
      given 1 mg/kg of body weight once a day in patients with idiopathic facial nerve
      paralysis.

PMID- 9546273
TI  - Blood distribution in the facial nerve in temporal bones acquired from cases with
      subarachnoid hemorrhage.
AB  - The objectives of this study, conducted in eight temporal bones from five
      autopsied cases of subarachnoid hemorrhage, were to delineate the communication
      between the cerebrospinal fluid space and each space of the epineurium,
      perineurium, and area surrounding the nerve fibers in the facial nerve and to
      identify the site of hypertonic diuretic solution infusion most likely to
      decrease the facial nerve swelling at the initial stage of facial palsy. In all
      eight specimens, blood cells had directly entered into each space from the
      labyrinthine segment of the facial nerve. The subarachnoid space extended to the
      first genu of the nerve. The genu, which is the site of the initial lesion in
      Bell's palsy, is concluded to be the most effective site of intracanal
      decompression of the facial nerve with hypertonic diuretic solution.

PMID- 9546274
TI  - Mitochondrial DNA deletion is a predisposing cause for sensorineural hearing
      loss.
AB  - Composed of a postmitotic stable tissue, the inner ear is a target organ for
      mitochondrial DNA (mtDNA) mutation. To determine whether mtDNA mutation is a
      predisposing factor in patients with sensorineural hearing loss (SNHL), the
      authors assessed the mtDNA4977 deletion from 60 patients with SNHL and 47 normal
      control subjects. All cases had no past history of ototoxic or noise exposure,
      middle ear disease, or other known etiological factors for SNHL. DNA specimens
      extracted from peripheral blood leukocytes were used for detection of mtDNA4977
      deletion by polymerase chain reaction. Patients with SNHL had a significantly
      higher rate of the mtDNA4977 deletion than did controls (75% vs. 30%, P <
      0.0001). The detection rate of mtDNA4977 deletion was significantly increased
      with the deterioration of the hearing threshold. Aging did not influence the
      detection rate of mtDNA4977 deletion in either the control or SNHL group. The
      authors have described high detection rates of the mtDNA4977 deletion in patients
      with idiopathic bilateral SNHL and propose that at least some of the advanced
      SNHL cases should be categorized as mitochondrial oxidative phosphorylation
      diseases. This inference would offer novel possibilities for treatment and
      prevention of SNHL including presbycusis.

PMID- 9546275
TI  - Changes in immunostaining of inner ears after antigen challenge into the scala
      tympani.
AB  - To study the mechanisms of immune responses and immune injuries in inner ears,
      labyrinthitis was induced by inoculation of keyhole limpet hemocyanin (KLH) into
      the scala tympani of systemically sensitized guinea pigs. Inner ears were then
      immunostained for KLH, immunoglobulin G (IgG), albumin, connexin26 (Cx26), and
      sodium-potassium adenosine triphosphate (Na,K-ATPase). Inflammatory cells
      containing KLH were observed in the scala tympani and in the collecting venule of
      the spiral modiolar vein (SMV). Spiral ligament, spiral limbus, and blood vessels
      including the SMV were diffusely positive for IgG and albumin. Immunoreactivity
      for Cx26 and Na,K-ATPase was decreased compared with the normal ears in the
      fibrocytes of the spiral ligament. These results suggest that inflammatory cells
      and blood constituents could extravasate into the cochlea from blood vessels and
      that fibrocyte damage in the spiral ligament could cause cochlear dysfunction.

PMID- 9546276
TI  - Effect of locally applied drugs on the endolymphatic sac potential.
AB  - In Meniere's disease, an inner ear disorder related to an endolymphatic hydrops,
      an alteration of the functioning of the endolymphatic sac has been proposed. The
      endolymphatic sac is assumed to be involved in the secretion/resorption of
      endolymph. The epithelial transport systems have been indirectly studied by the
      recording of the endolymphatic sac transepithelial potential (ESP) in control
      conditions and after the local injection of drugs such as diuretics that have
      been proposed in the treatment of Meniere's disease. The ESP was recorded, in
      vivo, in guinea pigs up to 150 minutes after the perisaccular injection of 5
      microL of a 150 mmol/L (mM) NaCl solution containing various drugs known to
      inhibit ionic transport systems. The initial ESP was +8.4+/-0.3 mV (mean +/- SEM,
      n = 78). The basolateral injection of 5 microL of 150 mM NaCl induced an ESP
      decrease of 64%+/-6.0% (n = 12), 5 minutes after the end of the injection. Then
      ESP increased, returning to its initial value at 60 minutes and surpassing it at
      120 minutes. Diuretics such as acetazolamide (10[-3] mol/L [M]), an inhibitor of
      carbonic anhydrase, and amiloride (10[-4] M), an inhibitor of Na channel or Na/H
      exchanger, decreased the ESP recovery. At variance, bumetanide (10[-6] M, 10[-4]
      M), the Na-K-Cl cotransport inhibitor, and chlorothiazide (10[-4] M), a Na-Cl
      cotransporter inhibitor, failed to alter the ESP as compared with the control
      group. Ouabain (10[-3] M), the Na+,K+-adenosine triphosphatase (ATPase)
      inhibitor, prevented the ESP recovery otherwise observed 60 minutes after the
      NaCl injection. Bafilomycin A1, the inhibitor of the vacuolar-type H+-ATPase,
      prevented the recovery of the ESP with a log-dose/effect (10[-5] M, 10[-6] M, 10[
      8] M). Disulfonic acid stilbene (DIDS) (10[-4] M), an inhibitor of transporters
      involving HCO3-, also prevented the ESP recovery. These results suggest that the
      genesis of the ESP was highly dependent on acid-base transport systems including
      carbonic anhydrase, a vacuolar-type H+-ATPase, and an anionic transport system
      blocked by DIDS. Further studies are needed to confirm the alteration of the acid
      base balance in this epithelium and its possible involvement in the pathogenesis
      of Meniere's disease.

PMID- 9546278
TI  - Is the presence of transient evoked otoacoustic emmissions in ears with acoustic
      neuroma significant?
AB  - One hundred sixty-eight patients admitted for acoustic neuroma removal were
      involved in this study. In all cases, the size of the tumor and the presence or
      absence of tinnitus and vertigo or dizziness were evaluated. Investigated
      functional procedures included bilateral measures of pure-tone audiometry (PTA),
      auditory brainstem response (ABR), electronystagmography (ENG), and transient
      evoked otoacoustic emissions (TEOAEs). Thirty-five patients (21%) had normal
      preoperative TEOAEs in the affected ear, whereas 133 patients (79%) failed to
      show reproducible responses. The aims of this study were 1. to evaluate what
      distinguishes patients with preoperative TEOAEs in the pathological ear (group A)
      from those who had no TEOAE (group B); and 2. to determine in cases of attempted
      hearing preservation whether preoperative TEOAE presence in the neuroma ear
      (group C) was predictive of postoperative hearing preservation compared with the
      group of patients without TEOAEs (group D). The presence of vertigo or dizziness
      was significantly less frequent, the age was lower, and preoperative mean PTA
      loss in both ears was lower in group A compared with group B. Frequency of the
      other studied parameters and ABR threshold were similar in both groups. When
      hearing preservation was attempted, the mean preoperative PTA loss of group C
      patients was lower in both ears compared with group D. However, postoperative
      mean PTA loss did not significantly differ in the two groups. In group C, the
      percentage of hearing preservation (66.6%) was significantly higher than the
      percentage of deafness (33.4%), whereas in group D the percentage of
      postoperative preserved audition and deafness did not significantly differ
      (respectively 44.4% and 55.6%). The findings suggest that 1. TEOAEs in ears with
      acoustic neuromas are found in younger patients with a lower preoperative mean
      PTA loss and are accompanied by fewer functional complaints, perhaps because
      preserved TEOAEs indicate a better preservation of inner ear vasculature; and, 2.
      along with radiological and electrophysiological investigations, TEOAE presence
      in the pathological ear could provide an additional criterion or predictive
      factor for the successful outcome of attempted hearing-conservation surgery in
      ears with acoustic neuromas.

PMID- 9546277
TI  - Imaging destructive lesions of the petrous apex.
AB  - Cholesterol granuloma and cholesteatoma are the two most common destructive
      lesions of the petrous apex. Arachnoid cyst is less common. These three expansile
      lesions are often indistinguishable on clinical grounds. Cholesterol granulomas
      can be treated effectively through internal drainage into the mastoid cavity or
      middle ear. Cholesteatomas, however, are managed by more aggressive and
      complicated removal, which often mandates the sacrifice of hearing. Symptomatic
      arachnoid cysts are amenable to simple surgical drainage. Therefore, accurate
      preoperative recognition on computed tomography (CT) and magnetic resonance
      imaging (MRI) is important in planning proper treatment. Thirteen cases of
      destructive lesions of the petrous apex are analyzed. The authors' experience
      illustrates that the "typical" CT and MRI radiographic features are diagnostic in
      some cases, but not in all. In this study the pathologic findings have been
      correlated with the radiologic features on both MRI and CT.

PMID- 9546279
TI  - Vestibular disease unmasked by hyperventilation.
AB  - Hyperventilation-induced dizziness is often thought to be psychogenic, but its
      effects in the presence of known vestibular disease have not been adequately
      examined. In this study hyperventilation was tested in two models of vestibular
      disease. These were, first, patients with profound unilateral vestibular deficit
      (prior translabyrinthine acoustic neuroma resection [postsurgery group]) and,
      second, patients with variable unilateral vestibular deficit (unoperated
      unilateral acoustic neuroma [presurgery group]). Patients were hyperventilated
      for 90 seconds. Using infrared videonystagmography, 100% of the 32 postsurgery
      patients and 82% of the 28 presurgery patients developed nystagmus with
      hyperventilation. Hyperventilation was more sensitive than head shake for
      eliciting nystagmus in these models. The false-positive rate for nystagmus in 29
      normal volunteers was 3.5% for hyperventilation and 10% for head shake. Our
      results show that hyperventilation can unmask underlying vestibular disease.

PMID- 9546280
TI  - Angiographic embolization for epistaxis: a review of 114 cases.
AB  - Angiography with selective embolization has become an accepted method of treating
      posterior epistaxis that is not controlled with conservative measures. The
      authors reviewed 112 cases of patients who had received selective angiographic
      embolization for refractory epistaxis from January 1990 to December 1995. There
      were 114 embolizations over this 5-year period. The immediate success rate was
      93%, with long-term success achieved in 88% of patients. The overall complication
      rate was 17%, with the long-term morbidity rate less than 1%. Selective
      angiographic embolization is a safe and effective method that should be
      considered in the treatment of refractory epistaxis.

PMID- 9546281
TI  - Pseudoepitheliomatous hyperplasia versus squamous cell carcinoma of the external
      auditory canal.
AB  - Four case reports are presented to demonstrate the clinical and histopathologic
      similarity of pseudoepitheliomatous hyperplasia (PH) to squamous cell carcinoma
      (SCC) in the external auditory canal (EAC). In all four cases the original report
      of SCC on a biopsy specimen of an EAC lesion was corrected on review to PH. In
      one patient conservative management resulted in resolution of the EAC lesion. A
      second patient underwent radiation therapy and partial temporal bone resection
      with no SCC found in the surgical specimen. A third patient's ear canal had
      healed with conservative treatment and repeated biopsy revealed no malignancy.
      After a 6-year symptom-free interval, she developed invasive SCC with bone
      involvement that required surgery and radiation treatment. A fourth patient
      underwent a sleeve resection of the skin of the EAC that proved to be PH, and no
      evidence of SCC was found. A thoughtful clinical history, careful physical
      examination, response to conservative treatment, and close communication with the
      pathologist should be exercised in the evaluation of EAC lesions.

PMID- 9546282
TI  - Three-dimensional analysis of cricoarytenoid joint motion.
AB  - The normal motion of the cricoarytenoid joint was characterized and analyzed in
      this study using seven fresh cadaver larynges mounted rigidly in an external
      fixator apparatus after radiopaque markers were attached to laryngeal landmarks.
      Fluoroscopic imaging and recording was performed of top, front, and side views
      while the arytenoid cartilages of each larynx were manipulated through the full
      range of motion from adduction to abduction. Computer video capture was performed
      of the recordings and editing of still frames accomplished to generate three
      dimensional plots of cricoarytenoid joint motion, which are shown in the
      manuscript. Selective and varying sequential disconnection of muscular and
      ligamentous structures to the arytenoid cartilage was achieved to determine their
      contributions to cricoarytenoid joint motion limitations and stability. The
      vocalis ligament, cricoarytenoid ligament, and conus elasticus are most important
      in controlling abduction, whereas the posterior cricoarytenoid muscle and conus
      elasticus are crucial in limiting adduction. The vocalis ligament prevents
      posterior displacement of the vocal process, while the cricoarytenoid ligament
      and a newly described ligament, the posterior capsular ligament, restricts
      anterior vocal process migration. Another ligament, the anterior capsular
      ligament, is described, which limits backward arytenoid cartilage tilting and
      lateral movement of the arytenoid cartilage on the cricoid cartilage facet.
      Section of the vocalis ligament with underlying conus elasticus produced
      reducible lateral arytenoid cartilage subluxation. Confirmation of cricoarytenoid
      joint facet relationships in full adduction and abduction was accomplished by
      fixation of the cricoarytenoid joints of one larynx in the two positions with
      adhesive, and subsequent exposure of the joint surfaces. Review of literature
      detailing human laryngeal embryological development shows that the glottis and
      arytenoid cartilages are formed in adduction, which explains how cricoarytenoid
      joint ligaments collaborate to achieve accurate vocal process approximation in
      adduction despite side-to-side asymmetries of the cricoarytenoid joint structures
      in the same larynges.

PMID- 9546283
TI  - Neuropathy associated with hyperoxaluria: improvement after combined renal and
      liver transplantations.
AB  - Little is known about oxaluria-associated neuropathy, and no effective treatments
      have been described. We report two patients with clinically severe and
      progressive sensorimotor polyneuropathy associated with oxaluria.
      Electrodiagnostic testing and sural nerve histopathology revealed evidence of
      severe axon loss and demyelination. In addition, birefringent crystalline
      deposits were identified within endoneurial and perineurial blood vessel walls,
      axon cylinders, and perimysial blood vessel walls. Electron probe microscopy
      confirmed that calcium (consistent with calcium oxalate) was a major constituent
      of the crystals. Both patients had substantial improvement in neuropathic signs
      and symptoms after kidney and liver transplantations despite no prior improvement
      with hemodialysis. Our results confirm previous reports of a mixed axonal and
      demyelinating neuropathy with calcium oxalate deposition in association with
      oxaluria. In addition, our findings suggest that renal and liver transplantation
      may be potential treatments for the associated neuropathy.

PMID- 9546284
TI  - BDNF up-regulates TrkB protein and prevents the death of CA1 neurons following
      transient forebrain ischemia.
AB  - The neurotrophin family of growth factors, which includes Nerve Growth Factor
      (NGF), Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT3) and
      Neurotrophin-4/5 (NT4/5) bind and activate specific tyrosine kinase (Trk)
      receptors to promote cell survival and growth of different cell populations. For
      these reasons, growing attention has been paid to the use of neurotrophins as
      therapeutic agents in neurodegeneration, and to the regulation of the expression
      of their specific receptors by the ligands. BDNF expression, as revealed by
      immunohistochemistry, is found in the pre-subiculum, CA1, CA3, and dentate gyrus
      of the hippocampus. Strong TrkB immunoreactivity is present in most CA3 neurons
      but only in scattered neurons of the CA1 area. Weak TrkB immunoreactivity is
      found in the granule cell layer of the dentate gyrus. Unilateral grafting of BDNF
      transfected fibroblasts into the hippocampus resulted in a marked increase in the
      intensity of the immunoreaction and in the number of TrkB-immunoreactive neurons
      in the granule cell layer of the dentate gyrus, pre-subiculum and CA1 area in the
      vicinity of the graft. No similar effects were produced after the injection of
      control mock-transfected fibroblasts. Delayed cell death in the CA1 area was
      produced following 5 min of forebrain ischemia in the gerbil. The majority of
      living cells in the CA1 area at the fourth day were BDNF/TrkB immunoreactive.
      Unilateral grafting of control mock-transfected or BDNF fibroblasts two days
      before ischemia resulted in a moderate non-specific protection of TrkB-negative,
      but not TrkB-positive cells, in the CA1 area of the grafted side. This finding is
      in line with a vascular and glial reaction, as revealed, by immunohistochemistry
      using astroglial and microglial cell markers. This astroglial response was higher
      in the grafted side than in the contralateral side in ischemic gerbils, but no
      differences were seen between BDNF-producing and non-BDNF-producing grafts.
      However, grafting of BDNF-producing fibroblasts two days before ischemia
      significantly and specifically prevented nerve cells from dying in the CA1 area
      of the ipsilateral hippocampus. Cell survival was associated with increased TrkB
      immunoreactivity as the majority of living cells were TrkB immunoreactive. Thus,
      our results show that BDNF is able to up-regulate the expression of TrkB in
      control and pathological states, and that BDNF prevention of neuronal death
      following transient forebrain ischemia is associated with increased expression of
      its specific receptor.

PMID- 9546285
TI  - Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL.
AB  - Twenty primary central nervous system lymphomas (PCNSL) from immunocompetent
      patients (nineteen B-cell lymphomas and one T-cell lymphoma) were investigated
      for genetic alterations and/or expression of the genes BCL2, CCND1, CDK4, CDKN1A,
      CDKN2A, MDM2, MYC, RB1, REL, and TP53. The gene found to be altered most
      frequently was CDKN2A. Eight tumors (40%) showed homozygous and two tumors (10%)
      hemizygous CDKN2A deletions. Furthermore, methylation analysis of six PCNSL
      without homozygous CDKN2A loss revealed methylation of the CpG island within exon
      1 of CDKN2A in three instances. Reverse transcription PCR analysis of CDKN2A mRNA
      expression was performed for 11 tumors and showed either no or weak signals.
      Similarly, immunocytochemistry for the CDKN2A gene product (p16) remained either
      completely negative or showed expression restricted to single tumor cells. None
      of the PCNSL showed amplification of CDK4. Similarly, investigation of CCND1
      revealed no amplification, rearrangement or overexpression. The retinoblastoma
      protein was strongly expressed in all tumors. Only one PCNSL showed a mutation of
      the TP53 gene, i.e., a missense mutation at codon 248 (CGG to TGG:Arg to Trp). No
      evidence of BCL2 gene rearrangement was found in 11 tumors investigated. The bcl
      2 protein, however, was strongly expressed in most tumors. None of the 20 PCNSL
      demonstrated gene amplification of MDM2, MYC or REL. In summary, inactivation of
      CDKN2A by either homozygous deletion or DNA methylation represents an important
      molecular mechanism in PCNSL. Mutation of the TP53 gene and alterations of the
      other genes investigated appear to be of minor significance in these tumors.

PMID- 9546286
TI  - Distribution of brain HIV load in AIDS.
AB  - Approximately one quarter of patients with AIDS develop severe cognitive deficits
      called HIV-associated dementia complex (ADC). There is some controversy regarding
      the importance of viral load in mediating neurologic disease. With the advent of
      sensitive, quantitative and reproducible RNA assays for HIV load in plasma and
      CSF, we quantified viral load in brains from 10 autopsied HIV-infected subjects
      and 2 non-infected controls. The new quantitative HIV RNA assays showed general
      agreement with previously used semi-quantitative immunocytochemical assessments
      of HIV envelope protein, and were performed without professional subjective
      interpretation. All cases with very high levels of HIV in the CSF, had high
      overall levels in the brain, suggesting that CSF viral loads exceeding 10(6)
      copies per mL may be a surrogate marker of high viral load in the brain. Levels
      of virus in the spleen showed no clear association with those found in the brain.
      HIV RNA was not uniformly distributed throughout the brain. Selective regions,
      including basal ganglia and hippocampus, showed higher levels of virus than the
      cerebellar cortex and mid-frontal cortical gray matter. Assessment of overall
      brain viral load requires careful attention to regional quantitation.

PMID- 9546288
TI  - Non-Alzheimer degenerative dementias.

PMID- 9546287
TI  - CD95 ligand: lethal weapon against malignant glioma?
AB  - CD95 (Fas/APO-1) and its ligand (CD95L) belong to a growing cytokine and cytokine
      receptor family that includes nerve growth factor (NGF) and tumor necrosis factor
      (TNF) and their corresponding receptors. CD95 expression increases during
      malignant progression from low-grade to anaplastic astrocytoma and is most
      prominent in perinecrotic areas of glioblastoma. There is, however, no evidence
      that CD95 expression in malignant gliomas is triggered by hypoxia or ischemia.
      Agonistic antibodies to CD95, or the natural ligand, CD95L, induce apoptosis in
      human malignant glioma cells in vitro. Glioma cell sensitivity to CD95-mediated
      apoptosis is regulated by CD95 expression at the cell surface and by the levels
      of intracellular apoptosis-regulatory proteins, including bcl-2 family members.
      Several cytotoxic drugs synergize with CD95L to kill glioma cells. For as yet
      unknown reasons, glioma cells may co-express CD95 and CD95L in vitro without
      undergoing suicide or fratricide. Yet, they kill T cells via CD95/CD95L
      interactions and are sensitive to exogenously added CD95L. Since CD95L is
      expressed in gliomas in vivo, too, forced induction of CD95 expression might
      promote therapeutic apoptosis in these tumors. That glioma cells differ from
      nontransformed T cells in their sensitivity to CD95 antibodies or recombinant
      ligand, may allow the development of selective CD95 agonists with high antitumor
      activity that spare normal brain tissue. A family of death ligand/receptor pairs
      related to CD95L/CD95, including APO2L (TRAIL) and its multiple receptors is
      beginning to emerge. Although several issues regarding glioma cell sensitivity to
      CD95L/CD95-mediated apoptosis await elucidation, CD95 is a promising target for
      the treatment of malignant glioma.

PMID- 9546289
TI  - Dementia with Lewy bodies. A distinct non-Alzheimer dementia syndrome?
AB  - Lewy body formation is central to the pathological phenotype of a spectrum of
      disorders. The most familiar of these is the extrapyramidal syndrome of
      idiopathic Lewy-body Parkinson's disease (PD). Studies of dementia in the elderly
      suggest that another manifestation of Lewy body pathology is equally or more
      common than Parkinson's disease. This syndrome of Dementia with Lewy bodies (DLB)
      has been given a number of diagnostic labels and is characterised by dementia,
      relatively mild parkinsonism, visual hallucinations, and fluctuations in
      conscious level. Although many of these features can arise in Parkinson's
      disease, the patients with DLB tend to have early neuropsychiatric features which
      predominate the clinical picture, and the diagnosis of the syndrome in practice
      is more concerned with the differential diagnosis of Alzheimer's disease (AD).
      Distinction from AD has clinical importance because of potentially differing
      therapeutic implications. Diagnostic guidelines for the clinical diagnosis and
      pathological evaluation of DLB are reviewed. Research into the disorder has
      centered around characterising the clinical, neuropsychological, pathological,
      neurochemical and genetic relationships with Alzheimer's disease on the one hand,
      and Parkinson's disease on the other. Many cases of DLB have prominent
      pathological features of AD and there are some shared genetic risk factors.
      Differences from the pathology of PD are predominantly quantitative rather than
      qualitative and evidence is discussed which suggests that DLB represents a
      clinicopathological syndrome within the spectrum of Lewy body disorders. The
      possibility that the syndrome represents a chance association of PD and AD is not
      supported by published studies.

PMID- 9546290
TI  - Dementia of frontal type and dementias with subcortical gliosis.
AB  - The group of Frontotemporal dementias (FTD) is composed of non-Alzheimer forms of
      dementia characterized clinically by behavioural and personality change leading
      to apathy and mutism. The disorder is associated with a progressive atrophy of
      the frontal, anterior temporal and anterior parietal lobes of the brain with
      several types of underlying pathology. One type (frontal lobe degeneration) is
      characterized by a microvacuolar degeneration of the outer cortical laminae along
      with a mild and mainly subpial gliosis and a loss of nerve cells, mostly from
      layers II and III. Another type shows transcortical tissue cavitation and florid
      gliosis with neuronal degeneration characterized by the presence of tau and
      ubiquitin positive inclusion bodies and alpha beta-crystallin-positive ballooned
      neurones: such changes have been termed 'Pick-type histology', and form the basis
      for the modern definition of 'Pick's disease'. The aetiological relationship
      between these two histological types is presently unknown. Both histologies can
      be differently distributed topographically throughout the brain to produce
      syndromes of progressive language disorder, when affecting bitemporal lobes or
      the left hemisphere preferentially, or progressive apraxia when parietal and
      motor regions are involved. Either pathology can be combined with or overlaps
      with that of classical motor neurone disease to produce motor neurone disease
      dementia. The underlying cause of FTD is unknown but genetic factors are strongly
      implicated. About half of cases show a previous family history of a similar
      disorder. In several families bearing a FTD clinical and pathological phenotype,
      linkage to chromosome 17 has been established but the pathology of this group
      appears distinctive and its relation to other forms of FTD awaits further
      elucidation. It is still possible that the many clinical and pathological
      variants of FTD may reflect different phenotypic expressions of a particular
      genetic change(s) at a single locus on this chromosome.

PMID- 9546291
TI  - Pick's disease: a modern approach.
AB  - Pick's disease is a rare dementing disorder that is sometimes familial. The
      cardinal features are circumscribed cortical atrophy most often affecting the
      frontal and temporal poles and argyrophilic, round intraneuronal inclusions (Pick
      bodies). Clinical manifestations reflect the distribution of cortical
      degeneration, and personality deterioration and memory deficits are often more
      severe than visuospatial and apraxic disorders that are common in Alzheimer's
      disease, but clinical overlap with other non-Alzheimer degenerative disorders is
      increasingly recognized. Neuronal loss and degeneration are usually maximal in
      the limbic system, including hippocampus, entorhinal cortex and amygdala.
      Numerous Pick bodies are often present in the dentate fascia of the hippocampus.
      Less specific features include leukoencephalopathy and ballooned cortical neurons
      (Pick cells). Glial reaction is often pronounced in affected cerebral gray and
      white matter. Tau-immunoreactive glial inclusions are a recently recognized
      finding in Pick's disease, and neuritic changes have also recently been
      described. Variable involvement of the deep gray matter and the brainstem is
      typical, with a predilection for the monoaminergic nuclei and nuclei of the
      pontine base. Neurochemical studies demonstrate deficits in intrinsic cortical
      neurotransmitter systems (e.g., somatostatin), but inconsistent loss of
      transmitters in systems projecting to the cortex (e.g., cholinergic neurons of
      the basal nucleus). Biochemical and immunocytochemical studies have demonstrated
      that abnormal tau proteins are the major structural components of Pick bodies. A
      specific tau protein immunoblotting pattern different from that seen in
      Alzheimer's disease and certain other disorders has been suggested in some
      studies. A specific molecular marker and a genetic locus for familial cases are
      not known.

PMID- 9546292
TI  - Corticobasal ganglionic degeneration and progressive supranuclear palsy
      presenting with cognitive decline.
AB  - Corticobasal ganglionic degeneration (CBGD) and progressive supranuclear palsy
      (PSP) were originally described in the sixties as predominantly motor syndromes.
      Over the years, the detailed study of additional cases of CBGD has shown that it
      is a distinctive histological entity which can often present as dementia or
      aphasia. Although some pathological features of CBGD overlap with those of other
      forms of non-Alzheimer non-Lewy body dementia, the distribution and relative
      number of these abnormalities and the distinctive pattern of tau immunodeposits
      allows the distinction of CBGD from Pick's disease and fronto-temporal dementia.
      In contrast, PSP only rarely presents with prominent dementia or behavioral
      changes. In these unusual PSP cases, care must be taken to exclude the diagnoses
      of CBGD and familial tangle-only dementia.

PMID- 9546293
TI  - Senile dementia with tangles (tangle predominant form of senile dementia).
AB  - Senile dementia with tangles is a sporadic subset of very late onset dementia
      with preponderance in females over age 80 years. Neuropathology shows diffuse
      cerebral atrophy with neurofibrillary tangles, often ghost tangles, and neuropil
      threads almost limited to limbic areas (transentorhinal, entorhinal area,
      hippocampuS--not exclusively sector CA 1--and amygdala) with only rare and mild
      involvement of the neocortex, basal ganglia and brainstem (except nucleus basalis
      and locus ceruleus), absence of neuritic plaques and absence or scarcety of
      amyloid deposits. This pattern of fibrillary pathology corresponds to Braak
      stages III and IV or the "limbic" type of Alzheimer disease that is considered
      the main form in the oldest-old but escapes the current criteria for the
      morphologic diagnosis of Alzheimer disease. It is distinct from other tau- or
      tangle-pathology related conditions, e.g. progressive supranuclear palsy,
      autosomal dominant dementia with tangles, and diffuse tangles with calcification.
      Very low prevalence of ApoE e4 allele (0.03-0.11%) and higher frequency of ApoE
      e3 and/or e2 suggest a lack of promoting effect of e4 and a possible protecting
      effect of e2/3 on amyloidogenesis. Senile dementia with tangles is suggested to
      be a variant of Alzheimer disease occurring in the oldest-old, but its
      nosological position within aging disorders of the brain is still controversy.

PMID- 9546294
TI  - Dementia with grains (argyrophilic grain disease).
AB  - Dementia with grains, also referred to as argyrophilic grain disease, is a
      morphological condition in elderly individuals histologically characterised by
      the widespread occurrence of minute, spindle or comma-shaped argyrophilic, tau
      immunoreactive structures distinct from neuropil threads that are predominantly
      located in the hippocampus and related limbic areas including the amygdala. They
      are suggested to arise mainly in dendrites of neurons showing accumulation of
      hyperphosphorylated tau proteins (pretangle stage) but not necessarily forming
      paired helical filaments. Argyrophilic grains are associated with argyrophilic,
      tau-positive oligodendroglial inclusions ("coiled bodies") in the white matter,
      while astroglia are not affected. Argyrophilic grain disease is considered to be
      a progressive disorder that may or may not be associated with dementia, the
      grains occasionally being the only morphologic substrates of cognitive decline.
      They often occur in combination with neuritic Alzheimer-type lesions (many
      corresponding to "limbic" Braak stages III and IV) or other neurodegenerative
      disorders, such as progressive supranuclear palsy, corticobasal degeneration, or
      Pick's disease. The prevalence and pathogenesis of this condition, its
      clinicopathologic correlations and nosological position among tau-pathology
      related disorders await further elucidation.

PMID- 9546295
TI  - Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of
      tauopathies.
AB  - Frontotemporal dementia is a neurological disorder characterised by personality
      changes, deterioration of memory and executive functions as well as stereotypical
      behaviour. Sometimes a Parkinsonian syndrome is prominent. Several cases of
      frontotemporal dementia are hereditary and recently families have been identified
      where the disease is linked to chromosome 17q21-22. Although, there is clinical
      and neuropathological variability among and within families, they all
      consistently present a symptomathology that has led investigators to name the
      disease "Frontotemporal Dementia and Parkinsonism linked to chromosome 17."
      Neuropathologically, these patients present with atrophy of frontal and temporal
      cortex as well as of basal ganglia and substantia nigra. In the majority of cases
      these features are accompanied by neuronal loss, gliosis and microtubule
      associated protein tau deposits which can be present in both neurones and glial
      cells. The distribution, structural and biochemical characteristics of the tau
      deposits differentiate them from those present in Alzheimer's disease,
      corticobasal degeneration, progressive supranuclear palsy and Pick's disease. No
      beta-amyloid deposits are present. The clinical and neuropathological features of
      the disease in these families suggest that Frontotemporal Dementia and
      Parkinsonism linked to chromosome 17 is a distinct disorder. The presence of
      abundant tau deposits in the majority of these families define this disorder as a
      new tauopathy.

PMID- 9546296
TI  - Establishing a pathological diagnosis in degenerative dementias.
AB  - While clinicopathological studies have confirmed that Alzheimer's disease (AD) is
      the most common neurodegenerative cause of dementia, these same studies have also
      revealed that other degenerative pathologies account for a significant proportion
      of patients with cognitive decline. Because pathological assessment of non
      Alzheimer neurodegenerative diseases now demands routine use of a costly panel of
      immunohistochemical techniques a scheme for staged examination of brain tissue
      has been developed. This scheme is weighted to initially screen out cases of
      Alzheimer's disease, dementia with Lewy bodies and vascular dementia using
      conventional staining methods and established diagnostic protocols, bringing in
      immunochemical techniques to discriminate between non-Alzheimer degenerative
      dementias. Diagnosis of pathologies causing the clinical syndrome of
      frontotemporal dementia can be ascertained using conventional staining
      supplemented by immunochemical detection of ubiquitin, tau protein and alpha beta
      crystallin. The diagnosis of prion disease is reliably confirmed by
      immunohistochemical detection of prion protein. This morphological assessment
      complements emerging genetic insights into many of these neurodegenerative
      diseases.

PMID- 9546297
TI  - Early Intervention Project: can its claims be substantiated and its effects
      replicated?
AB  - A comprehensive report to the National Institute of Health on the diagnosis,
      etiology, epidemiology, and treatment of autism indicated that early intervention
      has the potential of being an effective intervention (Bristol et al., 1996). In
      spite of this positive outlook, several research and methodological questions
      remain regarding time of treatment initiation, intensity of treatment and
      duration of treatment, random assignment, comparative treatment designs, and
      treatment integrity. Against this backdrop we consider the claims made by the
      Early Intervention Project (EIP; Lovaas, 1987, 1993; McEachin, Smith, & Lovaas,
      1993). The EIP claims to produce recovery from autism in 47% of the cases and to
      greatly reduce its severity in an additional 42% of cases. This article evaluates
      the EIP against threats to internal and external validity and is found to suffer
      from a number of methodological problems. Based on rebuttals to criticisms of
      their program, the EIP authors seem unwilling to admit any methodological flaws
      in the sampling, design, and analysis of data of the EIP. It is recommended that
      parents and fair hearing officers adopt an attitude of healthy skepticism before
      proceeding to an unqualified endorsement of the EIP as a treatment for autism.

PMID- 9546298
TI  - Home-based behavioral treatment of young children with autism.
AB  - This study evaluated the impact of intensive behavioral treatment on the
      development of young autistic children. The treatment reported in this study was
      home based and was implemented by parents of autistic children with the
      assistance of community-based clinicians. Although treatment was unable to be
      observed directly, parents reported that therapy was based on methods developed
      by Lovaas et al. (1981). Treatment differed from that described in previous
      reports of intensive behavior therapy for this population in that it was
      implemented outside an academic setting and for a shorter period. In addition,
      children received fewer hours per week of therapy than in previous reports.
      Children in the experimental treatment group were pairwise matched to children in
      a control group (who received conventional school-based and brief one-on-one
      interventions) on the basis of pretreatment chronological and mental age,
      diagnosis (autism vs. PDD), and length of treatment. The groups did not differ on
      pretreatment IQ. Children receiving the experimental treatment had significantly
      higher posttreatment IQ scores. Smaller, but still statistically significant
      effects on symptom severity were also found, though experimental subjects still
      met diagnostic criteria for autism or PDD.

PMID- 9546299
TI  - Effectiveness of a home program intervention for young children with autism.
AB  - This project evaluated the effectiveness of a TEACCH-based home program
      intervention for young children with autism. Parents were taught how to work with
      their preschool autistic child in the home setting, focusing on cognitive,
      academic, and prevocational skills essential to later school success. To evaluate
      the efficacy of the program, two matched groups of children were compared, a
      treatment group and a no-treatment control group, each consisting of 11 subjects.
      The treatment group was provided with approximately 4 months of home programming
      and was tested before and after the intervention with the Psychoeducational
      Profile-Revised (PEP-R). The control group did not receive the treatment but was
      tested at the same 4-month interval. The groups were matched on age, pretest PEP
      R scores, severity of autism, and time to follow-up. Results demonstrated that
      children in the treatment group improved significantly more than those in the
      control group on the PEP-R subtests of imitation, fine motor, gross motor, and
      nonverbal conceptual skills, as well as in overall PEP-R scores. Progress in the
      treatment group was three to four times greater than that in the control group on
      all outcome tests. This suggests that the home program intervention was effective
      in enhancing development in young children with autism.

PMID- 9546300
TI  - Does a photographic cue facilitate false belief performance in subjects with
      autism?
AB  - The posting manipulation, which Mitchell and Lacohee (1991) successfully employed
      to facilitate false belief (FB) task performance in normally developing 3-year
      olds, was employed with subjects with autism. There was no autism-specific
      impairment on the standard FB task, compared to mental handicap and normal
      controls: All groups performed poorly, with the autism and normal groups
      performing significantly worse than chance and the mental handicap group
      performing at chance. However, a facilitative effect was found on the posting FB
      task for all subject groups. On the posting task the mental handicap and normal
      controls groups performed significantly better than chance and the autism group
      performed at chance. The facilitative effect reached significance for the autism
      and normal groups. The lack of an autism-specific deficit on the standard task is
      discussed in relation to the somewhat variable findings of past studies of FB
      performance in autism. The facilitative effect of the posting manipulation may
      tell us something about the task demands required to pass a false belief task
      itself, and suggestions are made for future research to clarify how the
      facilitative effect operates.

PMID- 9546301
TI  - Source monitoring by children with autism.
AB  - The term "source monitoring" refers to the ability to distinguish the origins of
      memories. One type of source monitoring is reality monitoring-which means
      distinguishing internally and externally generated memories. This experiment
      examined reality monitoring by children with autism (with a mean mental age of 7
      years 8 months). The children said several words and listened to another person
      say similar words. The children were then given a surprise memory test and asked
      to identify which words they had said and which the other person had said. The
      children with autism were compared to matched groups of normal children and
      children with mental retardation. There were no differences between the groups
      and, at least for this task, there was no evidence that children with autism have
      a deficit in their reality monitoring abilities.

PMID- 9546302
TI  - Following the child's lead: mothers' interactions with children with autism.
AB  - This study examined the extent to which mothers of preschool children with autism
      use language that is related to the child's focus of attention. Fourteen mother
      child dyads involving preschool children with autism participated in this study,
      along with 14 matched dyads involving typically developing preschool children.
      Both groups were observed during 15 minutes of free play. Results revealed that
      the mothers of children with autism directed verbalizations to something within
      the child's focus of attention as frequently as the mothers of typically
      developing children. Thus, children with autism had as many opportunities to
      benefit from verbal input related to their focus of attention as did typically
      developing children. However, mothers of children with autism directed
      verbalizations to something not within the child's focus of attention more
      frequently than mothers of typically developing children. This nonrelated input
      may have reflected the mothers' attempts to adapt to their children's
      difficulties in attention and interaction.

PMID- 9546303
TI  - Abnormal saccadic eye movements in autistic children.
AB  - The saccadic eye movements, generated during a visual oddball task, of autistic
      children, normal children, children with attention deficit disorder and
      hyperactivity (ADDH), and dyslexic children were examined to determine whether
      autistic children differed from these other groups in saccadic frequency.
      Autistic children made more saccades during the presentation of frequent stimuli
      (than normals and ADDH children), and between stimulus presentations. Also,
      unlike the normal and dyslexic groups, their saccadic frequency did not depend on
      stimulus type. This abnormal pattern of saccades may negatively influence the
      ability to attend to stimuli, and thereby learning processes. Suggestions are
      made with respect to possible abnormalities in subcortical mechanisms involved in
      saccade generation.

PMID- 9546304
TI  - The Swedish version of the Childhood Autism Rating Scale in a clinical setting.
AB  - The Childhood Autism Rating Scale (CARS) is an instrument for screening and
      diagnosis of autism. The present study was performed to assess the interrater
      reliability of a Swedish version of the CARS when used in a clinical setting. The
      procedure used mimicked a frequent form of consultation in neuropsychiatry and
      pediatric neurology. During a restricted time period, both an interview with the
      parents and observation of the child take place. Often this assessment is an
      important screening procedure and directs further investigation. CARS was used
      for rating autistic behavior by two investigators in 25 children. A variant of
      the weighted kappa statistic (correcting for chance and for degrees of
      disagreement) showed values between .53 and .75 (indicating fair to excellent
      agreement). Aspects of validity and reliability are discussed.

PMID- 9546305
TI  - Validity of the Autism/Pervasive Developmental Disorder subscale of the
      Diagnostic Assessment for the Severely Handicapped-II.
AB  - This study was designed to establish the empirical validity of the Diagnostic
      Assessment for the Severely Handicapped-II (DASH-II) to screen for the presence
      of autism in severely and profoundly mentally retarded adults. Participants
      included 51 individuals residing in a large developmental center in Central
      Louisiana. The Autism/Pervasive Developmental Disorder subscale of the DASH-II
      was internally consistent. Additionally, the DASH-II was just as likely as the
      Childhood Autism Rating Scale (CARS) to classify autistic and control
      individuals. Specific items on the subscale were examined to identify those items
      most associated with a diagnosis of autism.

PMID- 9546306
TI  - Brief report: Control in highly focused top-spinning.

PMID- 9546307
TI  - Brief report: Degree of facilitator influence in facilitated communication as a
      function of facilitator characteristics, attitudes, and beliefs.

PMID- 9546308
TI  - Will your journal support parents advocating for intensive behavior therapy (the
      Lovaas method) as an entitlement under Part H of the Individuals with
      Disabilities Education Act?

PMID- 9546309
TI  - Does angiotensin I-converting enzyme inhibitor therapy have an antiproliferative
      effect on blood-forming bone marrow?

PMID- 9546310
TI  - Selective proliferation of lymphoid cells from lineage-c-Kit+ Sca-1+ cells by a
      clonal bone marrow stromal cell line.
AB  - To understand the regulatory mechanisms involved in the development of
      hematopoietic stem cells, we cultured lineage-negative, c-Kit+ Sca-1+ stem cells
      sorted from bone marrow cells by a fluorescence-activated cell sorter (FACS) on
      layers of bone marrow stromal cell lines established from SV40 T-antigen gene
      transgenic mice. We previously reported that the TBR59 stromal cell line induced
      two sequential cobblestone formations: the first formation committed to the
      myeloid and the second to the lymphoid lineage. After examination of many other
      bone marrow stromal cell lines, we found that TBR31-1 stromal cells supported
      only lymphoid development of the sorted stem cells. The sorted stem cells
      proliferated by forming cobblestones and the cells were released from the
      cobblestones. Most released cell populations were B220-positive lymphoid cells;
      cell production continued for 2 months. Addition of G-CSF or M-CSF produced only
      a slight effect on myeloid development. FACS analysis of the released cells
      showed that the B-lymphoid-committed progenitors developed into mature B-cells by
      expressing surface immunoglobulin M. These results indicate that TBR31-1 bone
      marrow stromal cells selectively support B-lymphoid development, whereas TBR59
      cells support both myeloid and lymphoid development of stem cells.

PMID- 9546311
TI  - Multiparameter-fluorescence activated cell sorting analysis of retroviral vector
      gene transfer into primitive umbilical cord blood cells.
AB  - Retroviral vector gene transfer strategies are currently being developed to treat
      a variety of hematopoietic disorders. To date, genetic modification of human
      pluripotent hematopoietic stem cells has been inefficient. In the present study
      we developed reagents and procedures for rapidly screening retroviral vector gene
      transfer conditions using a multiparameter fluorescence-activated cell sorting
      (FACS) assay. To identify transduced cells using FACS analysis, we developed a
      retroviral vector, termed MN, which stably expressed high levels of a truncated
      version of the low-affinity nerve growth factor receptor (LNGFR). In addition,
      procedures were developed for enriching CD34+ cells from cryopreserved umbilical
      cord blood. These cells were transduced with MN and evaluated using
      multiparameter FACS analysis for expression of CD34, CD38, and LNGFR. Stem cell
      maintenance was determined by measuring the CD34hi and CD34hiCD38lo/- cells
      remaining after ex vivo gene transfer. Gene transfer into these cells was
      measured by evaluating cells expressing high levels of LNGFR. Initial studies
      with this assay and with in vitro functional assays indicated that retroviral
      gene transfer following pre-incubation with a variety of cytokines in serum
      containing conditions resulted in 1) poor maintenance of hematopoietic stem cells
      and 2) gene transfer predominantly in relatively mature cells. When gene transfer
      in serum-free conditions was performed, some improvement was observed in the
      maintenance of cells retaining primitive immunophenotypes with no reduction in
      the gene transfer efficiency. The MN vector and multiparameter FACS analysis will
      be useful in efficiently screening ongoing efforts designed to improve stem cell
      gene transfer.

PMID- 9546312
TI  - IL-10 as an autocrine regulator of CSF secretion by monocytes: disparate effects
      on GM-CSF and G-CSF secretion.
AB  - In previous studies of endogenous granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) production, we
      found several differences in the secretion pattern within and between different
      cell systems; for example, CSF secretion by endothelial cells is not affected by
      any major downregulatory factors, whereas monocyte CSF secretion is modulated by
      several mechanisms. In this study, we characterized the factors that inhibit CSF
      secretion by monocytes. Three cytokines have inhibitory effects: interleukin (IL)
      4, IL-10, and IL-13. Among these, IL-4 and IL-10 have higher potency than IL-13.
      IL-4 and IL-13 affect GM-CSF and G-CSF secretion to the same extent. In contrast,
      exogenously added IL-10 has a stronger inhibitory effect on GM-CSF secretion than
      on G-CSF secretion. We also found that monocytes produce IL-10 with an autocrine
      downregulatory effect, and that this autocrine IL-10 reaches concentrations at
      which in most cases only GM-CSF (not G-CSF) secretion is significantly affected.
      We postulate that the disparate effect of IL-10 on monocyte secretion of the two
      CSFs reflects their physiological functions, with GM-CSF being mainly a
      proinflammatory cytokine working in the local compartment and G-CSF functioning
      mainly as a cell recruiting factor.

PMID- 9546313
TI  - Comparative phenotype mapping of normal vs. malignant pediatric B-lymphopoiesis
      unveils leukemia-associated aberrations.
AB  - Leukemic cells of B-lineage acute lymphoblastic leukemia (ALL) are regarded as
      the malignant counterparts of immature, physiologic B cell precursors (BCPs). To
      determine whether phenotypic differences exist between these corresponding cell
      types, we investigated samples of normal pediatric bone marrow (n=30) as well as
      of B-precursor ALL at diagnosis (n=53; common and pre-B subtype). Using three
      color multiparameter flow cytometric analysis, we compared the leukemic
      populations with the physiologic BCPs of corresponding maturity with respect to
      the intensity with which they expressed a series of antigens. In some of these
      antigens, leukemia-associated aberrations were frequently observed. In
      particular, overexpression of CD10 was displayed by 65% of ALL samples, whereas
      58% of leukemic cases aberrantly exhibited very low or no CD45RA expression.
      Regarding CD11a and CD44, 47% and 35% of ALL populations were aberrant as defined
      by either the absence or significant overexpression of the antigen. In contrast,
      antigen densities of CD49d, CD49e, and CD99 on leukemic cells were in the normal
      range of values for BCPs. Combining the patterns of frequently aberrant markers
      in a comprehensive analysis, we were able to identify individual phenotypic
      leukemic cell aberrations in up to 98% of investigated cases. CD10 and/or CD45RA
      were aberrant in 86% of cases overall, emphasizing the high discriminative
      potential of these two markers. Using comparative phenotype mapping based on
      quantitatively aberrant, leukemia-associated antigenic patterns, we were able to
      detect leukemic blasts among normal bone marrow cells at frequencies as low as
      10(-5). We speculate that our approach may have a profound impact on the
      development of new strategies for minimal residual disease investigations in
      patients with BCP-ALL.

PMID- 9546314
TI  - Sickling of nucleated erythroid precursors from patients with sickle cell anemia.
AB  - The pathophysiology of sickle cell anemia is primarily explained in terms of the
      oxygen-dependent polymerization of sickle hemoglobin (HbS) followed by sickling
      of erythrocytes. Since the rate and extent of HbS polymerization depend on its
      intracellular concentration, it has been generally assumed that sickling occurs
      primarily in mature erythrocytes with their high intracellular hemoglobin
      concentration. In the present study, we investigated the propensity of nucleated
      erythroid precursors to undergo sickling; both cultured and fresh marrow-derived
      erythroid precursors from patients with homozygous sickle cell anemia were
      studied. The results revealed that upon deoxygenation cultured erythroblasts
      underwent characteristic morphological deformation in the form of fine, fragile,
      elongated spicules. Ultrastructural analysis demonstrated highly organized and
      tightly aligned hemoglobin fibers in the protruded regions. Bone marrow cells
      examined under partial or complete deoxygenated conditions displayed similar
      morphological changes. When cultured SS erythroid precursors were exposed to
      hydroxyurea or butyrate, drugs that may increase fetal hemoglobin (HbF) and
      inhibit intracellular polymerization, a significant decrease was observed in the
      propensity of these precursors to undergo sickling, accompanied by a three- to
      fivefold increase in HbF. These results suggest that, in addition to mature
      erythrocytes, nucleated erythroid precursors in the bone marrow have the capacity
      to undergo characteristic sickling as a result of HbS polymerization and may be
      involved in several aspects of the pathophysiology of sickle cell anemia.
      Treatment with HbF-stimulating drugs may benefit patients with this disease by
      inhibiting polymerization-induced sickling of erythroid precursors in the marrow
      as well as mature erythrocytes in the peripheral blood.

PMID- 9546315
TI  - Repetitive bone marrow transplantation in nonmyeloablated recipients.
AB  - Transplantation of 200 million male BALB/c marrow cells into normal
      nonmyeloablated female BALB/c hosts results in relatively high levels of
      engraftment, whether the cells are infused repetitively over time or in a single
      infusion. These high engraftment rates suggested that repetitive injections of
      high levels of male BALB/c cells might be able to totally replace host marrow.
      Accordingly, we transplanted 40x10(6) male BALB/c bone marrow cells into female
      BALB/c recipients over a 7-week period for a total of 20 injections (800x10[6]
      marrow cells). Engraftment in this experimental group was compared to that seen
      when female recipients received 2x10(6) male marrow cells or phosphate-buffered
      saline (PBS) over the same injection schedule. Engraftment was quantitated at 5
      and 7 weeks after the final infusion by detection of male-specific sequences in
      female host marrow, spleen, and thymus by Southern blot analysis using a Y
      specific cDNA probe. Male DNA levels were quantitated with a Molecular Dynamics
      phosphorimager. Engraftment of male cells into female marrow at 5 and 7 weeks
      posttransplantation ranged from 19 to 88%, whereas that in spleen and thymus
      ranged between 30 and 100% and 28 and 50%, respectively. The mean percent
      engraftments for marrow, spleen, and thymus were 41, 69, and 39%, respectively.
      Mean percent engraftments for 2x10(6) cell infusions at 5 and 7 weeks for marrow,
      spleen, and thymus were 4, 6, and 4%, respectively. Marrow and spleen cellularity
      and total high proliferative potential colony-forming cell numbers were
      determined in PBS- and cell-injected mice. No significant differences between
      these groups were observed. For marrow engraftment, 20 injections of 40x10(6)
      cells was not more effective than five, but donor DNA in thymus and spleen was
      increased with 20 injections. Primitive progenitor cell levels and marrow
      cellularity do not increase in mice injected with large numbers of marrow cells,
      suggesting that host marrow cells are replaced rather than augmented by infused
      donor cells.

PMID- 9546316
TI  - Induction of L-histidine decarboxylase in a human mast cell line, HMC-1.
AB  - Histamine is an important mediator in allergic reactions, gastric acid
      secretions, and neurotransmission in the central nervous system. Basophils and
      mast cells are the main sources of histamine, which is formed from L-histidine by
      histidine decarboxylase (HDC). However, the regulatory mechanism of HDC in these
      cells remains unclear. We examined the regulation of HDC activity and gene
      expression using a unique human mast cell line, HMC-1, after stimulation with
      phorbol 12-myristate 13-acetate (PMA) or ionomycin. HDC activity was increased
      from 52.1+/-0.4 (mean+/-standard deviation) to 154+/-6.9, or 105.6+/-6.2
      pmol/min/mg protein (n = 3), 4 hours after stimulation with PMA (10 ng/mL) or
      ionomycin (10[-6] M). Although actinomycin D had no effect on this increase,
      cycloheximide completely inhibited the increase caused by these stimuli. The
      population of HMC-1 cells containing HDC protein was increased after stimulation
      with either PMA or ionomycin as evaluated by immunocytochemical analysis with
      anti-HDC antibody as a marker. HMC-1 constitutively expressed HDC mRNA, and its
      level was not increased with these stimuli. These results suggest that the
      increase of HDC activity in HMC-1 induced by PMA or ionomycin is regulated at the
      translational level.

PMID- 9546317
TI  - Mature human hematopoietic cells in donor bone marrow complicate interpretation
      of stem/progenitor cell assays in xenogeneic hematopoietic chimeras.
AB  - Xenogeneic hematopoietic chimeras have been used to assay the growth and
      differentiation of human stem/progenitor cells. The presence of human
      hematopoietic cells in immunodeficient mice transplanted with human marrow cells
      may be caused by proliferation and differentiation of early stem/progenitor cells
      and/or proliferation of mature cells. Unpurified human marrow mononuclear cells,
      T cell-depleted, or stem/progenitor cell-enriched (CD34+ or CD34+CD38-)
      populations were injected into sublethally irradiated NOD/LtSz scid/scid
      (NOD/SCID) mice. High levels of human cells were detected in mice (hu/mu
      chimeras) transplanted with each of the above human marrow populations. Large
      numbers of mature human T lymphocytes were found in marrow, spleens, and thymuses
      from hu/mu chimeras that had been transplanted with unpurified human mononuclear
      marrow cells. Human immunoglobulin was detected in sera from these chimeras, and
      some exhibited a clinical syndrome suggestive of graft-versus-host disease. In
      contrast, in hu/mu chimeras that had received T cell-depleted or stem/progenitor
      cell-enriched populations, multilineage hematopoiesis (myeloid, B lymphoid, and
      progenitor cells by immunophenotype) was detected but T lymphocytes and human
      immunoglobulin were not; in addition, no human cells were detected in the
      thymuses. Thus, injection of adult human marrow cells into immunodeficient mice
      can result in hematopoietic chimerism for at least 3 months after transplant.
      However, the types of cells present in hu/mu chimeras differ depending on the
      human cell population transplanted. This should be taken into account when
      hematopoietic chimeras are used to assess human stem/progenitor cell function.

PMID- 9546318
TI  - Distinct actions of Flt3 ligand and stem cell factor on myeloid lineage selection
      and maturation of granulocytes versus macrophages.
AB  - Flt3/Flk2 ligand (FL) and stem cell factor (SCF; c-kit ligand) interact with
      different but related surface receptor tyrosine kinases expressed on early
      hematopoietic cells. Both FL and SCF stimulate the proliferation of stem cells
      and progenitors, but the mechanisms by which these cytokines exert their
      functions are currently unknown. Here we show that FL and SCF have different
      effects on myeloid differentiation and lineage selection of early hematopoietic
      cells using a defined subpopulation of mouse bone marrow (BM) expressing c-Kit
      but lacking mature lineage markers (c-Kit+Lin-). SCF, together with IL-6, induced
      the differentiation of a large fraction of these progenitor cells toward mature
      granulocytes and to a lesser extent toward monocytes. In contrast, FL combined
      with IL-6 favored differentiation into mature monocytes and macrophages, and very
      few if any granulocytes could be identified. When FL and SCF were analyzed for
      their ability to support growth of multilineage erythroid colonies (pre-CFCmulti)
      and myeloid-committed colony-forming progenitors of granulocytes and monocytes
      (CFC-G/M), a clear discrepancy was also found. Both FL and SCF had synergistic
      effects on the proliferation of immature cells with blast-like morphology, but
      the expansion of pre-CFCmulti and CFC-G/M was favored by SCF but not by FL. FL
      synergized with both SCF and IL-6 with respect to proliferative response and
      maintenance of undifferentiated cells; however, the numbers of CFC-G/M after 7 or
      14 days in culture were significantly lower than those observed with SCF combined
      with IL-6. Interestingly, in contrast to SCF, no pre-CFCmulti was recovered from
      BM cells expanded in the presence of FL and IL-6.

PMID- 9546319
TI  - Human bone marrow CD34- cells engraft in vivo and undergo multilineage expression
      that includes giving rise to CD34+ cells.
AB  - We used the human/sheep competitive engraft model to investigate the in vivo
      engraftment potential of human CD34-, Lin- cells. In three separate studies,
      transplantation of CD34+, Lin- and CD34-, Lin- cells from the same normal human
      donors into preimmune fetal sheep resulted in long-term engraftment and
      multilineage hematopoietic cell/progenitor expression. Human cell/progenitor
      activities of the CD34+ group were CD3, 0.52%; CD13, 0.36%; CD45, 1.02%; glyA,
      1.78%; HLA-DR, 0.99%; colony-forming units (CFU)-Mix, 7.1%; and granulocyte
      macrophage CFU (CFU-GM), 13.7%; those of the CD34- group were CD3, 0.24%; CD45,
      2.49%; glyA, 0.75%; HLA-DR, 0.3%; CFU-Mix, 7.1%; and CFU-GM, 4.3%. Of special
      interest was the detection of highly significant numbers (1 x 10[9] cells) of
      human CD34+ cells in animals transplanted with CD34- cells. Secondary
      transplantation and limiting dilution studies confirmed the presence of cells
      with long-term engraftment potential in CD34- populations. The results presented
      here demonstrate that the CD34- fraction of normal human bone marrow contains
      cells capable of engraftment and differentiation into CD34+ progenitors and
      multiple lymphohematopoietic lineages in primary and secondary hosts.

PMID- 9546320
TI  - Prolonged febrile seizures and mesial temporal sclerosis.

PMID- 9546321
TI  - Magnetic resonance imaging evidence of hippocampal injury after prolonged focal
      febrile convulsions.
AB  - Magnetic resonance imaging (MRI) was performed after complex febrile convulsions
      (CFCs) in 27 infants. Definite MRI abnormalities were seen in 6 of the 15 infants
      with focal or lateralized CFCs and in none of the 12 infants with generalized
      CFCs. In 2 of the 6 infants with lateralized CFCs and abnormal MRIs, the MR
      images showed preexisting bilateral hippocampal atrophy consistent with the
      history of perinatal insults in these infants. However, the remaining 4 infants
      with MRI abnormalities and lateralized CFCs had significantly longer seizures
      than other infants and had MRI changes suggesting acute edema with increased
      hippocampal T2-weighted signal intensity and increased volume predominantly in
      the hippocampus in the hemisphere of seizure origin. Of those with acute edema, 1
      had electrographical seizure activity recorded in the temporal region and another
      had a choroid fissure cyst displacing the affected hippocampus; both infants had
      follow-up MRIs showing that hippocampal atrophy had developed. These patients
      demonstrate that prolonged and focal CFCs can occasionally produce acute
      hippocampal injury that evolves to hippocampal atrophy. Finally, evidence of
      preexisting hippocampal abnormalities in several infants and electrographical
      temporal lobe seizure activity in 1 suggests the possibility that CFCs actually
      originated in the temporal lobes in some patients.

PMID- 9546323
TI  - Epilepsies in twins: genetics of the major epilepsy syndromes.
AB  - We studied twins to examine the genetics of epilepsy syndromes. We ascertained
      358 twin pairs in whom one or both reported seizures. After evaluation, 253 of
      358 (71%) had seizure disorders and 105 pairs were false positives. Among the
      monozygous (MZ) pairs, more were concordant for seizures (48 of 108; casewise
      concordance = 0.62 +/- 0.05) than among the dizygous (DZ) pairs (14 of 145;
      casewise concordance = 0.18 +/- 0.04). In 94% of concordant MZ pairs, and 71% of
      concordant DZ pairs, both twins had the same major epilepsy syndrome. When
      analyzed according to major epilepsy syndrome, the casewise concordances for
      generalized epilepsies (MZ = 0.82; DZ = 0.26), both idiopathic (MZ = 0.76; DZ =
      0.33) and symptomatic (MZ = 0.83; DZ = 0), were greater than those for partial
      epilepsies (MZ = 0.36; DZ = 0.05), with intermediate values seen for febrile
      seizures (MZ = 0.58; DZ = 0.14) and unclassified epilepsies (MZ = 0.53; DZ =
      0.18). We conclude that genetic factors are particularly important in the
      generalized epilepsies but also play a role in the partial epilepsies. The high
      frequency of concordant MZ pairs with the same major syndrome strongly suggests
      there are syndrome-specific genetic determinants rather than a broad genetic
      predisposition to seizures.

PMID- 9546322
TI  - Matrix metalloproteinases MMP-9 and MMP-7 are expressed in experimental
      autoimmune neuritis and the Guillain-Barre syndrome.
AB  - Matrix metalloproteinases (MMPs) are a family of enzymes that may be implicated
      in the pathogenesis of inflammatory demyelinating disorders such as multiple
      sclerosis. The present study investigated the expression of 92-kd gelatinase (MMP
      9) and five other MMPs in sciatic nerve from Lewis rats with autoimmune
      experimental neuritis (EAN), an experimental model of the Guillain-Barre syndrome
      (GBS). Quantitative polymerase chain reaction analysis revealed an up-regulation
      of MMP-9 mRNA with peak levels concurrent with maximal disease severity.
      Increased mRNA expression was associated with enhanced enzyme activity, as
      detected by gelatin zymography. Immunohistochemically, MMP-9 could be localized
      primarily around blood vessels within the epineurium and endoneurium in diseased
      but not normal sciatic nerve. Among all other MMPs investigated, mRNA levels of
      matrilysin (MMP-7) were found to be up-regulated at the peak of the disorder,
      remaining at high levels throughout the clinical recovery phase of the disease.
      To apply these findings to human disease, sural nerve biopsies from GBS patients
      were examined. By using immunohistochemistry, positive immunoreactivity against
      MMP-9 and MMP-7 was noted and corroborated by demonstrating augmented mRNA
      expression in comparison with noninflammatory neuropathies. Furthermore,
      increased MMP-9 activity was detected by zymography. These findings indicate that
      92-kd gelatinase and matrilysin are selectively up-regulated during EAN and
      expressed in nerves of GBS patients and thus may contribute to the pathogenesis
      of inflammatory demyelination of the peripheral nervous system.

PMID- 9546325
TI  - Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients
      to oxidative stress.
AB  - Although the cause of amyotrophic lateral sclerosis (ALS) is unkNown, free
      radical toxicity is thought to play a pathogenic role. We investigated whether
      cells from ALS patients are more vulnerable to exogenously induced oxidative
      stress than cells from controls. We therefore studied the sensitivity of
      fibroblasts from patients with sporadic ALS (SALS), and from patients with
      familial ALS (FALS) associated with copper/zinc superoxide dismutase (Cu/ZnSOD)
      mutations (SOD1-FALS), to the free radical-generating agents 3
      morpholinosydnonimine (SIN-1) and hydrogen peroxide (H2O2), and to serum
      withdrawal. SOD1-FALS and SALS fibroblasts were significantly more sensitive than
      controls to SIN-1 but not to serum withdrawal. In addition, SOD1-FALS fibroblasts
      were more sensitive to H2O2 than SALS fibroblasts and than fibroblasts of
      controls. These results suggest that the mechanism underlying both SOD1-FALS and
      SALS jeopardizes the cell's defense against free radical stress, and that SOD1
      FALS cells are particularly sensitive to H2O2. The latter finding is compatible
      with biochemical data on the increased affinity of the mutated Cu/ZnSOD for H2O2.

PMID- 9546326
TI  - Purified IgG from seropositive and seronegative patients with mysasthenia gravis
      reversibly blocks currents through nicotinic acetylcholine receptor channels.
AB  - The mechanism of block of nicotinic acetylcholine receptor (nAChR) channels by
      purified antibodies from patients with myasthenia gravis (MG) was investigated by
      using an ultrafast system for solution exchange at outside-out patches. IgG of MG
      patients and controls was purified by using protein A-Sepharose columns. Probes
      from 9 seropositive MG patients and 3 seronegative MG patients were tested. As a
      preparation, cultured mouse myotubes expressing the embryonic-type nAChR channels
      were used. Twenty-millisecond pulses of 1.0 mM ACh were applied repetitively to
      outside-out patches. Outside-out patches were preexposed with IgG in
      concentrations between 0.1 and 200 mg/L during application of ACh pulses. The
      peak current amplitude was reduced to values between 6% and 71% of control for
      the 9 seropositive and 3 seronegative MG patients. The block was concentration
      dependent and fully reversible after washout of antibodies. Incubation with IgG
      from different control patients did not reduce the peak current amplitude. In
      addition, our findings with purified IgG from seronegative MG patients support
      the idea of the immunopathogenesis of this disorder and may allow the development
      of a diagnostic test for seronegative MG patients.

PMID- 9546324
TI  - Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy.
AB  - We recently reported the frequent occurrence of polycystic ovaries and
      hyperandrogenism associated with weight gain and hyperinsulinemia in women taking
      valproate for epilepsy. The purpose of this study was to evaluate the risks
      related to valproate-induced hyperinsulinemia and their reversibility after
      discontinuing the medication. Sixteen women with valproate-related polycystic
      ovaries or hyperandrogenism participated in the study. Vaginal ultrasonography
      was performed, and endocrine and lipid parameters were measured. Thereafter,
      lamotrigine was substituted for valproate and the patients were observed for 12
      months. Twenty-four healthy age-matched women served as control subjects. Twelve
      women completed the 12-month follow-up. While still on valproate they had
      centripetal obesity with associated hyperinsulinemia and unfavorable serum lipid
      profiles. The body-mass index and fasting serum insulin and testosterone
      concentrations decreased during the first year after replacing valproate with
      lamotrigine whereas the HDL-cholesterol/total cholesterol ratios increased from
      0.17 +/- 0.06 to 0.26 +/- 0.05. The total number of polycystic ovaries in these
      women decreased from 20 during valproate medication to 11 one year after
      replacing valproate with lamotrigine. Valproate induces a metabolic syndrome with
      centripetal obesity, hyperinsulinemia, lipid abnormalities, and polycystic
      ovaries/hyperandrogenism in women with epilepsy. These valproate-related risks
      can be reduced by substituting lamotrigine for valproate.

PMID- 9546327
TI  - Multiple sclerosis: in situ evidence for antibody- and complement-mediated
      demyelination.
AB  - We describe a case of multiple sclerosis characterized by deposition of
      immunoglobulin and complement in the areas of active demyelination. This was
      particularly evident for the C9neo antigen, which is a marker for the activated
      lytic complement complex and was exclusively deposited in the areas of active
      myelin destruction. In addition, macrophages in the lesions contained degradation
      products that were immunoreactive for myelin antigens, immunoglobulins, and C9neo
      antigen. Destruction of myelin sheaths was associated with incomplete loss of
      oligodendrocytes in the active areas and reappearance of oligodendrocytes with
      remyelination in the inactive plaque center.

PMID- 9546328
TI  - Cortical reflex myoclonus in Rett syndrome.
AB  - Rett syndrome (RS) is one of the most frequent causes of mental retardation in
      females. As there are no known biochemical, genetic, or morphological markers,
      diagnosis is based on clinical phenotype including severe dementia, autism,
      truncal ataxia/apraxia, loss of purposeful hand movements, breathing
      abnormalities, stereotypies, seizures, and extrapyramidal signs. Myoclonus,
      although reported in some series, has never been characterized. We studied 10 RS
      patients, age 3 to 20 years, and observed myoclonus in 9. Severity of myoclonus
      did not correlate with that of the other symptoms or with age. Multifocal,
      arrhythmic, and asynchronous jerks mainly involved distal limbs.
      Electromyographic bursts lasted 48 +/- 12 msec. Burst-locked
      electroencephalographic averaging generated a contralateral centroparietal
      premyoclonus transient preceding the burst by 34 +/- 7.2 msec. Motor evoked
      potentials showed normal latencies, indicating integrity of the corticospinal
      pathway. Somatosensory evoked potentials were enlarged. The C-reflex was
      hyperexcitable and markedly prolonged (62 +/- 4.3 msec), mainly due to increase
      in cortical relay time (28.4 +/- 4.5 msec). We conclude that RS patients show a
      distinctive pattern of cortical reflex myoclonus with prolonged intracortical
      delay of the long-loop reflex.

PMID- 9546329
TI  - Quinidine sulfate therapy for the slow-channel congenital myasthenic syndrome.
AB  - The slow-channel congenital myasthenic syndrome (SCCMS) is caused by gain of
      function mutations in subunits of the end-plate acetylcholine receptor (AChR).
      The mutations prolong the opening episodes of the AChR channel, leading to a
      depolarization block and an end-plate myopathy. Because levels of quinidine
      sulfate attainable in clinical practice shorten the opening episodes of
      genetically engineered mutant SCCMS receptors in vitro, we tested the notion that
      the drug can be of benefit in SCCMS. We treated 6 SCCMS patients with quinidine
      sulfate in an open-label trial, using objective clinical measures of muscle
      strength and repetitive stimulation studies as end points. One patient became
      allergic to quinidine after 7 days. The remaining patients tolerated the drug
      well and after 30 days of continuous therapy showed statistically significant
      improvement in muscle strength and in decrement of the compound muscle action
      potential elicited by rapid rates of stimulation.

PMID- 9546330
TI  - Angelman syndrome: correlations between epilepsy phenotypes and genotypes.
AB  - We compared epilepsy phenotypes with genotypes of Angelman syndrome (AS),
      including chromosome 15q11-13 deletions (class I), uniparental disomy (class II),
      methylation imprinting abnormalities (class III), and mutation in the UBE3A gene
      (class IV). Twenty patients were prospectively selected based on clinical
      cytogenetic and molecular diagnosis of AS. All patients had 6 to 72 hours of
      closed-circuit television videotaping and digitized electroencephalogrpahic (EEG)
      telemetry. Patients from all genotypic classes had characteristic EEGs with
      diffuse bifrontally dominant high-amplitude 1- to 3-Hz notched or triphasic or
      polyphasic slow waves, or slow and sharp waves. Class I patients had severe
      intractable epilepsy, most frequently with atypical absences and myoclonias and
      less frequently with generalized extensor tonic seizures or flexor spasms.
      Epileptic spasms were recorded in AS patients as old as 41 years. Aged-matched
      class II, III, and IV patients had either no epilepsy or drug-responsive mild
      epilepsy with relatively infrequent atypical absences, myoclonias, or atonic
      seizures. In conclusion, maternally inherited chromosome 15q11-13 deletions
      produce severe epilepsy. Loss-of-function UBE3A mutations, uniparental disomy, or
      methylation imprint abnormalities in AS are associated with relatively mild
      epilepsy. Involvement of other genes in the chromosome 15q11-13 deletion, such as
      GABRB3, may explain severe epilepsy in AS.

PMID- 9546331
TI  - The role of type III collagen in spontaneous cervical arterial dissections.
AB  - A case-control study was carried out to investigate whether type III collagen
      deficiency plays a role in the pathogenesis of spontaneous cervical arterial
      dissections. In 16 patients with spontaneous cervical arterial dissections and in
      41 healthy controls, protein analysis of type III collagen (ratio of type
      III/type I collagen) was performed. Furthermore, single-stranded conformation
      polymorphism/heteroduplex analysis was used to investigate the type III collagen
      gene in the 16 patients with spontaneous cervical dissections to detect
      mutations. The ratios of type III/type I collagen in the controls ranged from 5.5
      to 19.8% (median, 10%). The ratios of type III/type I collagen in the patients
      with spontaneous cervical arterial dissections ranged from 3.2 to 17.9% (median,
      9.3%). Two patients had a low ratio of type III/type I collagen (<5.5%). No
      abnormalities suggesting a mutation in the gene of type III collagen were
      demonstrated in any of the 16 patients. Our findings are in keeping with the
      hypothesis that a reduced production of type III collagen may contribute to the
      formation of spontaneous cervical arterial dissections in some patients. The
      absence of a responsible mutation indicates that the coding sequence of the type
      III collagen gene is not involved.

PMID- 9546332
TI  - Guidelines for using quantitative measures of brain magnetic resonance imaging
      abnormalities in monitoring the treatment of multiple sclerosis.
AB  - The change of brain lesion load, measured on T2-weighted magnetic resonance
      imaging (MRI) using computer-assisted techniques, is a widely used secondary
      endpoint for phase III clinical trials in multiple sclerosis (MS). Collection,
      transfer, and analysis of the electronic data across multiple centers have all
      proved challenging and give rise to potential errors. However, many new
      acquisition schemes and postprocessing techniques have been developed; these may
      reduce scan times and result in better lesion conspicuity or lessen the human
      interaction needed for data analysis. This review considers many aspects of the
      use of MRI in clinical trials for MS and provides international consensus
      guidelines, derived from a task force of the European Magnetic Resonance Networks
      in Multiple Sclerosis (MAGNIMS) together with a group of North American experts.
      The main points considered are the organization of correctly powered trials and
      selection of participating sites; the appropriate choice of pulse sequences and
      image acquisition protocol given the current state of technology; quality
      assurance for data acquisition and analysis; accuracy and reproducibility of
      lesion load assessments; and the potential for the application of quantitative
      methods to other MRI-derived measures of disease burden.

PMID- 9546333
TI  - Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke
      dyskinesia in parkinsonian monkeys.
AB  - Treatment of Parkinson's disease with L-dopa therapy leads to long-term
      complications, including loss of drug efficacy and the onset of dyskinesia.
      Adenosine A2A receptors in striatum are selectively localized to GABAergic output
      neurons of the striato-pallidal pathway and may avoid such problems. The novel
      adenosine A2A receptor antagonist KW-6002 has been examined for antiparkinsonian
      activity in MPTP-treated primates. Oral administration of KW-6002 reversed motor
      disability in MPTP-treated common marmosets in a dose-dependent manner. However,
      KW-6002 only modestly increased overall locomotor activity and did not cause
      abnormal movement, such as stereotypy. The ability of KW-6002 to reverse motor
      disability was maintained on repeated daily administration for 21 days, and no
      tolerance was observed. KW-6002 induced little or no dyskinesia in MPTP-treated
      primates previously primed to exhibit dyskinesia by prior exposure to L-dopa.
      These results suggest that selective adenosine A2A receptor antagonists represent
      a new class of antiparkinsonian agents that improve disability without producing
      hyperactivity and without inducing dyskinesia.

PMID- 9546334
TI  - Paroxysmal tonic upgaze: a reappraisal of outcome.
AB  - Paroxysmal tonic upgaze (PTU) of childhood is a distinctive neuro
      ophthalmological syndrome of unknown etiology and pathogenesis that is
      characterized by episodes of sustained upward deviation of the eyes, often with
      incomplete downward saccades on attempted downgaze. It is generally regarded as
      having a benign outcome. We observed 16 children with PTU, from 10 months to 11
      years from onset (mean, 5.4 years), to study the natural history and possible
      etiology. Five cases were from two unrelated families. Onset of PTU occurred
      either during or after an intercurrent infection or vaccination in 5 children. No
      antecedent was identifiable in the rest. PTU had completely resolved in 10
      children (62%) (mean age at offset, 2.5 years), whereas 2 children intermittently
      manifest a modified form of the disorder. At follow-up, 11 children (69%) had
      developmental delay, intellectual disability, or language delay and 9 (56%) had
      ocular motility problems other than PTU. Only 3 children (19%) had normal
      development and neurological findings. PTU is a heterogeneous syndrome with
      respect to associations and outcome and may simply be an age-dependent
      manifestation of a variety of disorders affecting corticomesencephalic control of
      vertical eye movement. This disorder may be an early sign of more widespread
      neurological dysfunction.

PMID- 9546335
TI  - Cerebrospinal fluid homovanillic acid levels in rapid-onset dystonia
      parkinsonism.
AB  - Rapid-onset dystonia-parkinsonism (RDP) is characterized by sudden onset over
      hours to days of dystonia, dysphagia, dysarthria, and parkinsonism. RDP has been
      reported by our group in two apparently unrelated families. We now report
      analysis of cerebrospinal fluid metabolites of dopamine, norepinephrine, and
      serotonin for mild and severely affected individuals, known asymptomatic gene
      carriers, and at-risk individuals from both families with RDP. Levels of the
      dopamine metabolite homovanillic acid (HVA) were decreased in severely affected
      patients and in some asymptomatic gene carriers. HVA levels increased with
      treatment in some affected individuals, but this increase did not predict
      clinical response to carbidopa/levodopa. We suggest that a low HVA level is a
      biological marker with modest association to the diagnosis of RDP.

PMID- 9546336
TI  - A permanent pure amnestic syndrome of insidious onset related to Alzheimer's
      disease.
AB  - A 55-year-old patient experienced a pure amnestic syndrome of insidious onset
      that worsened progressively. Subsequently, her memory disorder stabilized and
      remained her only cognitive impairment for several years. She ultimately
      developed more widespread cognitive decline and terminal dementia. Postmortem
      examination 18 years after the onset revealed numerous senile plaques and
      neurofibrillary tangles consistent with Alzheimer's disease. A permanent pure
      amnestic syndrome of insidious onset may represent a further type of focal
      cerebral degeneration.

PMID- 9546337
TI  - Clinical demographics of multiplex families with multiple sclerosis. Multiple
      Sclerosis Genetics Group.
AB  - The demographic and clinical characteristics of 89 multiplex families whose
      affected members meet proposed diagnostic criteria for multiple sclerosis (MS)
      genetic research are described and compared with 425 sporadic cases of MS and
      other published collections of MS multiplex families. The proportion of affected
      multiplex family members who experienced gradual progression of disability from
      onset (primary progressive MS) is lower than reported by other investigators.
      Different phenotypes of MS may reflect genetic heterogeneity that may partially
      explain inconsistencies in the results of genetic linkage studies. Clinical
      details of affected multiplex family members must be described so that
      comparisons of genetic results across studies can be properly interpreted.

PMID- 9546338
TI  - Optic neuritis heralding varicella zoster virus retinitis in a patient with
      acquired immunodeficiency syndrome.
AB  - We report on a 29-year-old severely compromised acquired immunodeficiency
      syndrome patient who developed retrobulbar optic neuritis 5 weeks after an
      episode of cutaneous herpes zoster infection. During the optic neuritis,
      varicella zoster virus could be demonstrated in the cerebrospinal fluid. The
      neuritis responded well to treatment with foscarnet, but, 3 weeks into therapy,
      varicella zoster retinitis developed. Additional treatment with intravenous
      acyclovir stopped progression of the retinitis and resulted in healing of the
      retinal lesions. This case suggests that retrobulbar optic neuritis can be
      regarded as a prodrome of imminent acute retinal necrosis. Early recognition and
      prompt therapy with combined antivirals may prevent the development of this
      devastating ocular complication of varicella zoster infection.

PMID- 9546340
TI  - Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset.
AB  - Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a
      severe disorder of mitochondrial beta-oxidation in infants. We report adult onset
      of attacks of painful rhabdomyolysis. Gas chromatography identified strongly
      elevated levels of tetradecenoic acid, 14:1(n-9), tetradecadienoic acid, 14:2(n
      6), and hexadecadienoic acid, 16:2(n-6). Palmitoyl-CoA and behenoyl-CoA
      dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low.
      DNA analysis revealed compound heterozygosity for two missense mutations in the
      VLCAD gene. The relatively mild clinical course may be due to residual enzyme
      activity as a consequence of the two missense mutations. Treatment with L
      carnitine and medium chain triglycerides in the diet did not reduce the attacks
      of rhabdomyolysis.

PMID- 9546339
TI  - Neurotrophin-4 is up-regulated in ragged-red fibers associated with pathogenic
      mitochondrial DNA mutations.
AB  - Ragged-red fibers (RRFs) are found more frequently in highly oxidative type I
      fibers than in glycolytic type II fibers in the muscle of many patients with
      mitochondrial myopathies. Neurotrophin-4 (NT-4), a neuronal signaling molecule,
      is also expressed in skeletal muscle, predominantly in type I fibers. We found
      that NT-4 protein and mRNA were present in both type I and type II fibers but
      were up-regulated in RRFs of patients with mitochondrial encephalomyopathies; it
      is noteworthy that NT-4 was not up-regulated in muscle fibers from healthy
      aerobically trained athletes. Thus, NT-4 might represent a member of a new class
      of candidate molecules involved in the compensatory adjustments of muscle fibers
      to oxidative dysfunction, and may even play a role as a signaling molecule for
      mitochondrial proliferation.

PMID- 9546341
TI  - APOE allele frequencies in demented and nondemented elderly Jamaicans.

PMID- 9546342
TI  - Preserved tendon reflexes in Campylobacter neuropathy.

PMID- 9546343
TI  - Gap junction function: the messenger and the message.

PMID- 9546344
TI  - Regulation of uveal melanoma interconverted phenotype by hepatocyte growth
      factor/scatter factor (HGF/SF).
AB  - Human uveal melanoma disseminates initially and preferentially to the liver. This
      study describes the relationship between the expression of the c-met proto
      oncogene (receptor for hepatocyte growth factor/scatter factor (HGF/SF)) in
      interconverted uveal melanoma cells (co-expressing vimentin and keratin
      intermediate filaments) and the regulation of their motogenic response to HGF/SF,
      a key step in local invasion and targeted dissemination to the liver. Expression
      of c-met in uveal melanoma cell lines correlates with both the appearance of an
      interconverted phenotype and invasive ability (measured in vitro). Using
      chemotactic checkerboard analysis, the greatest motogenic response to HGF/SF was
      achieved by invasive, interconverted, c-met-positive uveal melanoma cells. C-met
      was observed histologically in a uveal melanoma containing interconverted cells
      but was absent in a tumor composed of non-interconverted cells (vimentin
      positive/keratin negative). The c-met ligand, HGF/SF, although not expressed by
      uveal melanoma cell lines, was localized in tissue sections of primary uveal
      melanomas and metastatic melanoma to the liver. In the primary tumor, staining
      for HGF/SF was most intense at the level of the choriocapillaris, a finding that
      is significant because 1) highly remodeled neovascular loops and networks, which
      appear in tumors likely to disseminate, can be traced to the choriocapillaris and
      the draining vortex veins and 2) HGF/SF plays a role in tumor angiogenesis. Foci
      of metastatic melanoma to the liver stain diffusely for HGF/SF. Regulation of the
      uveal melanoma interconverted phenotype by HGF/SF may play an important role in
      the dissemination of this tumor.

PMID- 9546345
TI  - Nasopharyngeal carcinomas frequently lack the p16/MTS1 tumor suppressor protein
      but consistently express the retinoblastoma gene product.
AB  - The p16/MTS1 gene is altered by deletion, mutation, or hypermethylation in a wide
      variety of human cancers. As a result of deficient p16 protein, these cancers
      lack a critical mechanism for halting G1/S cell cycle progression. In the current
      study, 59 cases of nasopharyngeal carcinoma were evaluated for expression of the
      p16 tumor suppressor protein by immunohistochemical analysis of paraffin-embedded
      tissue. There was no detectable p16 in 38/59 cases (64%), which implies a very
      high rate of p16 inactivation in this type of cancer. On the other hand, the
      retinoblastoma gene product, which also regulates the G1 to S phase transition of
      the cell cycle, was consistently expressed in nasopharyngeal carcinomas by
      immunohistochemical analysis. These results implicate p16 inactivation but not Rb
      alteration in the stepwise progression of nasopharyngeal carcinogenesis.

PMID- 9546346
TI  - Evidence of oxidative stress and in vivo neurotoxicity of beta-amyloid in a
      transgenic mouse model of Alzheimer's disease: a chronic oxidative paradigm for
      testing antioxidant therapies in vivo.
AB  - Increased expression of antioxidant enzymes and heat-shock proteins are key
      markers of oxidative stress. Such proteins are abnormally present within the
      neuropathological lesions of Alzheimer's disease (AD), suggesting that oxidative
      stress may play significant but yet undefined roles in this disorder. To gain
      further insight into the role of oxidative stress in AD, we studied the
      expression of CuZn superoxide dismutase (SOD) and hemoxygenase-1 (HO-1), two
      established markers of oxidative stress, in a transgenic mouse model of AD.
      Immunohistochemistry with anti-SOD and anti-HO-1 antibodies revealed a very
      pronounced increase of these proteins only in aged transgene-positive mice.
      Interestingly, the distribution of the oxidative burden was largely overlapping
      with dystrophic neuritic elements in the mice as highlighted with anti-ubiquitin
      antibodies. Because the most conspicuous alterations were identified around
      amyloid (Abeta) deposits, our results provide strong support for the hypothesis
      that Abeta is neurotoxic in vivo and that such toxicity is mediated by free
      radicals. To obtain additional experimental evidence for such an interpretation
      (ie, a cause-effect relationship between Abeta and oxidative neurotoxicity), PC12
      cells were exposed to increasing concentrations of Abeta or to oxidative stress.
      In agreement with the in vivo findings, either treatment caused marked induction
      of SOD or HO-1 in a dose-dependent fashion. These results validate the transgenic
      approach for the study of oxidative stress in AD and for the evaluation of
      antioxidant therapies in vivo.

PMID- 9546347
TI  - Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and
      dementia with Lewy bodies.
AB  - Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of
      patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB).
      Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein
      protein was identified in some autosomal-dominantly inherited familial PD
      pedigrees, and light microscopic studies demonstrated alpha-synuclein
      immunoreactivity in LBs of sporadic PD and DLB. To characterize alpha-synuclein
      in LBs, we raised monoclonal antibodies (MAbs) to LBs purified from DLB brains
      and obtained a MAb specific for alpha-synuclein that intensely labeled LBs. Light
      and electron microscopic immunocytochemical studies performed with this MAb as
      well as other antibodies to alpha-and beta-synuclein showed that alpha-synuclein,
      but not beta-synuclein, is a component of LBs in sporadic PD and DLB. Western
      blot analyses of highly purified LBs from DLB brains showed that full-length as
      well as partially truncated and insoluble aggregates of alpha-synuclein are
      deposited in LBs. Thus, these data strongly implicate alpha-synuclein in the
      formation of LBs and the selective degeneration of neurons in sporadic PD and
      DLB.

PMID- 9546348
TI  - RNA synthesis and splicing interferes with DNA in situ end labeling techniques
      used to detect apoptosis.
AB  - The detection of DNA fragmentation by the use of the TUNEL technique has become a
      standard technique for the detection of apoptosis in tissue sections. DNA
      cleavage, detected by the TUNEL technique, is the last irreversible stage of the
      apoptosis cascade. When the nuclear DNA is cleaved in oligonucleosomal-sized
      fragments, processes such as transcription are completely abolished. The values
      of apoptotic cell death that were obtained for atherosclerotic plaques by the
      TUNEL technique ranged from less than 2% up to 60%. The latter value would
      indicate that plaques are in an imminent state of collapse, which is certainly
      not the case. Other factors that could result in TUNEL labeling have to be
      considered. Therefore, we developed a co-localization system and studied TUNEL
      labeling together with markers of RNA transcription and splicing. The present
      study demonstrates that, besides apoptotic nuclei, non-apoptotic nuclei that show
      signs of active gene transcription are labeled by the TUNEL technique. The fact
      that the TUNEL technique is not specific for the executive phase of apoptosis is
      not surprising, as the technique is only selective (rather than specific) for
      apoptotic nuclei as these contain a far greater degree of DNA fragmentation than
      non-apoptotic nuclei. Therefore, we think that the TUNEL technique should be
      combined with additional techniques, such as markers of transcription and
      morphological criteria.

PMID- 9546350
TI  - Biotin-labeled hairpin oligonucleotides: probes to detect double-strand breaks in
      DNA in apoptotic cells.
AB  - Hairpin oligonucleotides were synthesized with stems ending in a double-stranded
      structure, which can be ligated to double-strand breaks in DNA, and with loops
      that contain nucleotides modified by the attachment of biotin. These probes
      specifically and sensitively detect double-strand breaks in apoptotic cells.
      Localization of these probes is restricted to areas of chromatin characteristic
      of apoptosis, whereas much more diffuse labeling was obtained when all available
      3' DNA ends were labeled by terminal transferase. In principle, hairpin
      oligonucleotide probes can be designed with any type of 3' or 5' overhang
      complementary to double-strand DNA termini being detected.

PMID- 9546349
TI  - Light and electron microscopic immunolocalization of presenilin 1 in abnormal
      muscle fibers of patients with sporadic inclusion-body myositis and autosomal
      recessive inclusion-body myopathy.
AB  - Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle
      disease of older persons. The muscle biopsy demonstrates mononuclear cell
      inflammation and vacuolated muscle fibers containing paired helical filaments and
      6- to 10-nm fibrils, both resembling those of Alzheimer disease brain and Congo
      red positivity. The term hereditary inclusion-body myopathies (h-IBMs) designates
      autosomal-recessive or autosomal-dominant disorders with muscle biopsies
      cytopathologically similar to s-IBM but without inflammation. Vacuolated muscle
      fibers of both s-IBM and the h-IBMs contain accumulations of several "Alzheimer
      characteristic proteins" including beta-amyloid protein and beta-amyloid
      precursor protein, and their paired helical filaments are composed of
      phosphorylated tau. We used six well characterized antibodies against several
      residues of presenilin 1 (PS1) to immunostain muscle biopsies of 12 patients with
      s-IBM, 5 patients with autosomal-recessive inclusion-body myopathy, and 16 normal
      and disease controls. Seventy to eighty percent of the vacuolated muscle fibers
      of both s-IBM and autosomal-recessive inclusion-body myopathy had inclusions that
      were strongly PS1-immunoreactive, which by immunoelectron microscopy localized
      mainly to paired helical filaments and 6- to 10-nm filaments. None of the control
      biopsies had PS1-positive inclusions characteristic of the s- and h-IBM abnormal
      muscle fibers. Mutations of the newly discovered PS1 gene are responsible for
      early-onset familial Alzheimer disease (AD), and PS1 is abnormally accumulated in
      sporadic and familial AD brain. Our study provides the first demonstration of PS1
      abnormality in non-neural tissue and in diseases other than AD and suggests that
      the cytopathogenesis in AD brain and IBM muscle may share similarities.

PMID- 9546351
TI  - A quantitative method for determination of endothelial mRNA expression in vivo:
      induction of platelet-derived growth factor by endotoxin.
AB  - Quantitation of mRNA expression by endothelial cells in vivo has been limited to
      larger animals from which sufficient amounts of RNA could be isolated for
      Northern blot analysis. In the present study, we established a technique to
      isolate endothelial RNA from rat aortas using en face preparations. This RNA was
      not contaminated with RNA from smooth muscle cells as demonstrated by the absence
      of smooth muscle alpha-actin RNA. Following lipopolysaccharide (LPS)
      administration to rats, quantitation of platelet-derived growth factor (PDGF)
      ligand and receptor mRNA expression was carried out by competitive reverse
      transcriptase-polymerase chain reaction and normalized to glyceraldehyde-3
      phosphate dehydrogenase. The results of the competitive reverse transcriptase
      polymerase chain reaction were compared with those obtained by en face in situ
      hybridization. Aortic endothelium showed a 140-fold increase in PDGF-A mRNA
      expression 4 hours after LPS injection. Expression levels of this growth factor
      declined to near base line levels within 36 hours of the LPS injection. A 52-fold
      increase in PDGF-B mRNA was seen at 12 hours after LPS injection but expression
      levels were approximately 300-fold lower than for PDGF-A. These data indicate
      that changes in PDGF expression by endothelium in vivo can greatly exceed those
      observed in cultured cells. This method should permit study of endothelial gene
      regulation in a variety of pathological conditions in vivo.

PMID- 9546352
TI  - Clonal architecture of normal and atherosclerotic aorta: implications for
      atherogenesis and vascular development.
AB  - X chromosome inactivation studies indicate that smooth muscle cells in human
      atherosclerosis are monoclonal. Monoclonality could arise either by 1)
      proliferation of a single cell in the adult intima, eg, by selection or mutation,
      or 2) proliferation of many cells within a large, pre-existing clonal patch that
      formed during development. To determine whether clonal expansion occurs
      concomitantly with plaque growth or as part of normal development, X chromosome
      inactivation patterns were mapped in microdissected samples of aortic smooth
      muscle, using the human androgen receptor locus as a marker. As expected, 43% of
      plaque samples were skewed toward one X chromosome, indicating a monoclonal
      population. Surprisingly, 25% of normal medial samples and 31% of diffuse intimal
      thickening samples also were skewed toward one X chromosome, indicating a
      relatively large patch size. Furthermore, 30% of diffuse intimal thickening and
      22% of medial samples showed contiguous regions of 4 mm skewed to the same
      allele, showing that patch length often exceeded 4 mm. Intima and overlying media
      typically were skewed to the same allele (73% concordance), suggesting common
      cells of origin. Because patch size is large in normal arteries, X-inactivation
      analysis cannot discriminate between a monoclonal and a polyclonal origin of
      plaque smooth muscle cells. We propose that human arteries grow by expanding
      coherent smooth muscle clones, with little mixing of adjacent clones. Determining
      whether plaques arise by clonal expansion will require other approaches, such as
      analysis of somatic mutations; the finding of large X-inactivation patches raises
      the possibility that plaques arise from a pre-existing (developmental) clone.

PMID- 9546353
TI  - Temporal expression of pro-inflammatory cytokines and inducible nitric oxide
      synthase in experimental acute Chagasic cardiomyopathy.
AB  - To characterize the kinetics of myocardial cytokine and inducible nitric oxide
      synthase (iNOS) expression in acute Chagasic cardiomyopathy, we studied a rat
      model of acute Trypanosoma cruzi infection. Rats were euthanized 36 hours and 5,
      10, and 15 days after infection, and hearts were collected for histology, mRNA,
      and protein analyses. Histological analysis of myocardium showed a progressive
      increase in the number of amastigotes and mononuclear inflammatory cells.
      Organisms were first detected 5 days after intraperitoneal inoculation as
      isolated nests and became numerous by day 15. Northern blot analysis of total RNA
      revealed no signal for interleukin (IL)-1beta or tumor necrosis factor (TNF)
      alpha and a weak signal for IL-6 in control hearts. High levels of expression for
      the three genes were detected in the infected animals at 36 hours after
      infection. Although IL-1beta and IL-6 levels increased steadily up to 10 days,
      TNF-alpha levels were the highest at 5 days, remained high at 10 days, and
      declined thereafter. Western blot analysis showed similar results to that of mRNA
      expression. No signal was detected for iNOS in the controls, but both its mRNA
      and protein were found in the infected animals, with levels being highest at 15
      days after infection. Immunohistochemistry revealed no iNOS immunoreactivity in
      uninfected animals, but intense iNOS staining was detected in blood vessels of
      infected animals, which decreased progressively with period of infection.
      Positive staining for iNOS in cardiomyocytes was first detected at 36 hours after
      infection (at a time when there was no histological inflammatory reaction), which
      steadily increased, being the highest at 15 days after infection. These results
      indicate that, in addition to mechanical damage by T. cruzi, substantial pro
      inflammatory cytokine production within the myocardium is likely to participate
      in the pathophysiology of acute Chagasic cardiomyopathy.

PMID- 9546354
TI  - Compound heterozygosity for missense (L156P) and nonsense (R554X) mutations in
      the beta4 integrin gene (ITGB4) underlies mild, nonlethal phenotype of
      epidermolysis bullosa with pyloric atresia.
AB  - Mutations in the genes encoding the subunit polypeptides of the alpha6beta4
      integrin (ITGA6 and ITGB4, respectively) have been previously demonstrated in
      patients with a lethal form of epidermolysis bullosa with congenital pyloric
      atresia (OMIM #226730). In this study, we demonstrate for the first time ITGB4
      mutations in nonlethal phenotype of epidermolysis bullosa with congenital pyloric
      atresia. Specifically, the proband was shown to be a compound heterozygote for a
      missense mutation (L156P) and a nonsense mutation (R554X). The leucine
      substitution by proline was shown to affect a residue, which was precisely
      conserved in different human, rodent, and drosophila integrin-beta polypeptides,
      and consequently disrupts the alpha-helix formation of the polypeptide segment as
      determined by Garnier alpha-helicity plot. The nonsense mutation in another
      allele was accompanied by undetectable levels of the corresponding mRNA
      transcript, as determined by reverse transcription-polymerase chain reaction. The
      presence of a missense mutation, when combined with a premature termination codon
      mutation, may explain the milder blistering tendency of the skin in this patient.

PMID- 9546355
TI  - Identification of cell types responsible for bone resorption in rheumatoid
      arthritis and juvenile rheumatoid arthritis.
AB  - Focal resorption of bone at the bone-pannus interface is common in rheumatoid
      arthritis (RA) and juvenile rheumatoid arthritis (JRA) and can result in
      significant morbidity. However, the specific cellular and hormonal mechanisms
      involved in this process are not well established. We examined tissue sections
      from areas of bone erosion in patients with RA and JRA. Multinucleated cells
      (MNCs) were present in resorption lacunae in areas of calcified cartilage and in
      subchondral bone immediately adjacent to calcified cartilage, as previously
      described. mRNA for the calcitonin receptor (CTR) was localized to these MNCs in
      bone resorption lacunae, a finding that definitively identifies these cells as
      osteoclasts. These MNCs were also positive for tartrate-resistant acid
      phosphatase (TRAP) mRNA and TRAP enzymatic activity. Occasional mononuclear cells
      on the bone surface were also CTR positive. Mononuclear cells and MNCs not on
      bone surfaces were CTR negative. The restriction of CTR-positive cells to the
      surface of mineralized tissues suggests that bone and/or calcified cartilage
      provide signals that are critical for the differentiation of hematopoietic
      osteoclast precursors to fully differentiated osteoclasts. Some MNCs and
      mononuclear cells off bone and within invading tissues were TRAP positive. These
      cells likely represent the precursors of the CTR-TRAP-positive cells on bone.
      Parathyroid hormone receptor mRNA was present in cells with the phenotypic
      appearance of osteoblasts, in close proximity to MNCs, and in occasional cells
      within pannus tissue, but not in the MNCs in bone resorption lacunae. These
      findings demonstrate that osteoclasts within the rheumatoid lesion do not express
      parathyroid hormone receptor. In conclusion, the resorbing cells in RA exhibit a
      definitive osteoclastic phenotype, suggesting that pharmacological agents that
      inhibit osteoclast recruitment or activity are rational targets for blocking
      focal bone erosion in patients with RA and JRA.

PMID- 9546357
TI  - Human CTLA-4 is expressed in situ on T lymphocytes in germinal centers, in
      cutaneous graft-versus-host disease, and in Hodgkin's disease.
AB  - Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is a molecule
      expressed on in vitro activated T cells. CTLA-4 shares important sequence
      homology with CD28 and binds to the same ligands, CD80 (B7-1) and CD86 (B7-2).
      CTLA-4 probably functions as a negative regulator of T lymphocyte activation in
      the mouse, although this remains to be proven for human T lymphocytes. We have
      developed new monoclonal antibodies against human CTLA-4 and have investigated
      the in situ expression of CTLA-4 in a wide variety of normal and pathological
      human tissues expressing CD80 and CD86. As revealed in this study, CTLA-4 is
      expressed on thymocytes in thymic medulla, on a subset of CD4+ T lymphocytes in
      germinal centers of follicular hyperplasia, on T cells, mainly CD8+, infiltrating
      skin affected by graft-versus-host disease, and on T cells, mainly CD4+,
      infiltrating Hodgkin's disease lesions. In immunoelectron microscopy, CTLA-4 was
      found on the plasma membrane as well as in the hyaloplasm and cytoplasmic
      vesicles, in agreement with its pattern of expression on in vitro activated T
      cells. Interestingly, no or at most scarce expression of CTLA-4 was found in
      granulomatous lymph nodes, T-cell-mediated inflammatory diseases, or non
      Hodgkin's lymphomas, regardless of their expression of CD80 or CD86. Thus,
      expression of CTLA-4 appears to be induced in selective pathological conditions
      in vivo. The pathways leading to selective induction of CTLA-4 and its role in
      the pathophysiology of these conditions need to be further investigated.

PMID- 9546358
TI  - Time course and cellular localization of interleukin-10 mRNA and protein
      expression in autoimmune inflammation of the rat central nervous system.
AB  - Experimental autoimmune encephalomyelitis of the Lewis rat is a T-cell-mediated
      autoimmune disease of the central nervous system characterized by a self-limiting
      monophasic course. In this study, we analyzed the expression of the anti
      inflammatory cytokine interleukin (IL)-10 at the mRNA and protein level in
      experimental autoimmune encephalomyelitis actively induced with the
      encephalitogenic 68-86 peptide of guinea pig myelin basic protein.
      Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL
      10 mRNA expression peaked during the acute phase of the disease at days 11 and
      13. IL-10 mRNA was synchronously induced with mRNA for the proinflammatory
      cytokine interferon-gamma. Immunocytochemistry with a monoclonal antibody against
      rat IL-10 showed that the peak of IL-10 mRNA was accompanied by an abundant
      expression of IL-10 protein during the acute stage of the disease. Both in situ
      hybridization and double labeling immunocytochemistry in combination with
      confocal microscopy identified T cells, macrophages/microglia, and astrocytes as
      major cellular sources of IL-10 in vivo. The early peak of IL-10 production was
      unexpected in light of its well-documented anti-inflammatory properties.
      Additional studies are required to determine whether endogenous IL-10 contributes
      to rapid clinical remission typical for Lewis rat experimental autoimmune
      encephalomyelitis or if it plays other, yet undefined, roles in central nervous
      system autoimmunity.

PMID- 9546356
TI  - Tubular up-regulation of clusterin mRNA in murine lupus-like nephritis.
AB  - Clusterin, a widely distributed glycoprotein, is detected in most tissues and in
      numerous physiological fluids. In the kidney, this protein is constitutively
      expressed in tubular epithelial cells, and its expression is enhanced following
      tubular injuries. In addition, clusterin has been detected in glomerular immune
      deposits of glomerulonephritis. The present study was designed to define the
      sites of clusterin mRNA accumulation in murine lupus-like nephritis in comparison
      with murine tubulopathies. In lupus-like nephritis, a significant increase of
      clusterin mRNA abundance was demonstrated. This up-regulation was localized
      exclusively in tubular epithelial cells exhibiting tubulointerstitial
      alterations, whereas no clusterin mRNA was detectable in diseased glomeruli,
      excluding an active synthesis of clusterin by glomerular cells. A similar tubular
      increase of clusterin mRNA abundance was observed in myeloma-like cast
      nephropathy induced by IgG3 monoclonal cryoglobulins and even in the absence of
      any detectable histological alterations in a model of septic shock induced by the
      injection of bacterial lipopolysaccharides. Our results suggest that tubular
      epithelial cells are the only sites of clusterin mRNA accumulation during the
      course of lupus-like nephritis and that the tubular up-regulation of clusterin
      gene expression may reflect the cellular response to various types of tubular
      injuries.

PMID- 9546359
TI  - Astrocytes containing amyloid beta-protein (Abeta)-positive granules are
      associated with Abeta40-positive diffuse plaques in the aged human brain.
AB  - Amyloid beta-protein (Abeta) is the major component of senile plaques that emerge
      in the cortex during aging and appear most abundantly in Alzheimer's disease. In
      the course of our immunocytochemical study on a large number of autopsy cases, we
      noticed, in many aged nondemented cases, the presence of unique diffuse plaques
      in the cortex distinct from ordinary diffuse plaques by immunocytochemistry. The
      former were amorphous, very faintly Abeta-immunoreactive plaques resembling
      diffuse plaques, but they stained for Abeta40 and were associated with small
      cells containing Abeta-positive granules. A panel of amino- and carboxyl-terminal
      specific Abeta antibodies showed that such Abeta40-positive diffuse plaques and
      cell-associated granules were composed exclusively of amino-terminally deleted
      Abeta terminating at Abeta40, -42, and -43. Double immunostaining also showed
      that those Abeta-immunoreactive granules are located in astrocytes and not in
      microglia or neurons. Immunoelectron microscopy revealed that nonfibrillar Abeta
      immunoreactivity was located within lipofuscin-like granules in somewhat swollen
      astrocytes. These findings raise the possibility that astrocytes take up Abeta
      and attempt to degrade it in lysosomes in the aged brain.

PMID- 9546360
TI  - Connexin43 gap junctions in normal, regenerating, and cultured mouse bone marrow
      and in human leukemias: their possible involvement in blood formation.
AB  - Communicating channels called gap junctions are thought to play a ubiquitous part
      in cell growth and development. Based on earlier work, we have recently found
      functional evidence of their presence in human and mouse bone marrow. In this
      study we studied the cell-type association of the gap junction channel-forming
      protein, connexin, in mouse and human bone marrow under different physiological
      and pathological conditions and tested the pathway of communication in bone
      marrow cultures. For high-resolution antigen demonstration we took advantage of
      semi-thin resin sections, antigen retrieval methods, immunofluorescence, and
      confocal laser scanning microscopy. Connexin43 (Cx43) and its mRNA were
      consistently expressed in human and rodent marrow. Cx37 was found only in the
      arteriolar endothelium, but neither Cx32 nor -26 were expressed. In tissue
      sections, the immunostained junctions appeared as dots, which were digitally
      measured and counted. Their average size was 0.40 mm in human and 0.49 mm in mice
      marrow. There were at least twice as many gap junctions in the femoral midshaft
      of 6-week-old mice (1.75 x 10(5)/mm3) as in those older than 12 weeks (0.89 x
      10(5)/mm3). Most Cx43 was associated with collagen III+ endosteal and adventitial
      stromal cells and with megakaryocytes. Elsewhere, they were few and randomly
      distributed between all kinds of hematopoietic cells. In the femoral epiphysis of
      juvenile mice, stromal cell processes full of Cx43 enmeshed three to six layers
      of hematopoietic cells near the endosteum. The same pattern was seen in the
      midshaft of regenerating mouse marrow 3 to 5 days after cytotoxic treatment with
      5-fluorouracil. Functional tests in cultures showed the transfer of small
      fluorescent dyes, Lucifer Yellow and 2',7'-bis-(2-carboxyethyl)-5, 6
      carboxyfluorescein, between stromal cells and in rare cases between stromal and
      hematopoietic cells too. The stromal cells were densely packed with Cx43 and we
      found aggregates of connexon particles in their membrane replicas. In
      normocellular human bone marrow, gap junctions were as rare as in adult mouse and
      similarly distributed, except that they were also on adipocytic membranes. In a
      few leukemic samples, characterized by an increased stromal/hematopoietic cell
      ratio, there were two- to fourfold more Cx43 (2.8 x 10(5) to 3.9 x 10(5)/mm3)
      than in the normal (1.0 x 10(5) to 1.2 x 10(5)/mm3). The cases included a
      hypoplastic acute lymphoblastic leukemia, an acute myeloid leukemia (French
      American-British classification M4-5), a case of myelodysplastic syndrome with
      elevated number of megakaryocytes, and a CD34+ acute hemoblastosis, probably
      acute myeloid leukemia (French-American-British classification M7). Taken
      together, our results indicate that direct cell-cell communication may be
      involved in hematopoiesis, ie, in developmentally active epiphyseal bone marrow
      and when there is a demand for progenitors in regeneration. However, gap
      junctions may not play as important a role in resting adult hematopoiesis and in
      leukemias.

PMID- 9546361
TI  - Distinct expression profiles of stromelysin-2 (MMP-10), collagenase-3 (MMP-13),
      macrophage metalloelastase (MMP-12), and tissue inhibitor of metalloproteinases-3
      (TIMP-3) in intestinal ulcerations.
AB  - Programmed expression of matrix metalloproteinases is involved in wound healing
      in various organs. We have previously demonstrated enhanced expression of
      collagenase-1, stromelysin-1, matrilysin, and tissue inhibitor of
      metalloproteinases (TIMP-1) in gastrointestinal ulcerations. To further define
      the role of matrix-degrading enzymes and their inhibitors in intestinal
      inflammation and ulcerations, the expression of stromelysin-2 (MMP-10),
      collagenase-3 (MMP-13), macrophage metalloelastase (HME, MMP-12), and TIMP-3
      mRNAs was studied using in situ hybridization and immunohistochemistry in 38
      samples representing ulcerative colitis, Crohn's disease, ischemic colitis, and
      normal intestine. As controls for normally healing intestinal wounds, 12
      postoperative samples of rat experimental jejunal anastomoses were also examined.
      The colitis types studied did not essentially differ in their MMP expression. We
      found stromelysin-2 mRNA in laminin-5-positive and Ki-67-negative enterocytes
      bordering the ulcerations. HME was abundantly expressed by macrophages in the
      vicinity of shedding mucosal epithelium and beneath the necrotic surface of the
      ulcers. Collagenase-3 and TIMP-3 were expressed by fibroblast-like cells deeper
      in the remodeling intestinal wall. Expression for stromelysin-2 and collagenase-3
      was observed in granulation tissue, but not the epithelium, of the rat
      anastomoses. Our results suggest a role for stromelysin-2 in epithelial migration
      and for metalloelastase in macrophage movement and epithelial cell shedding.

PMID- 9546362
TI  - Post-transcriptional induction of p21cip1 protein in condylomata and dysplasias
      is inversely related to human papillomavirus activities.
AB  - Infections of the genital and oral epithelia by human papillomaviruses cause
      condylomata, papillomas, and squamous intraepithelial neoplasms, some of which
      can progress to invasive cancers. We describe an induction of p21cip1/WAF1/sdi1
      protein in a fraction of the spinous cells in benign lesions and in cervical
      intraepithelial neoplasia grades I and II. The induction appears to be post
      transcriptional and independent of p53. p21cip1 antigen-positive cells were
      sporadic in cervical intraepithelial neoplasia III and rare and focal in
      carcinomas. In contrast, p21cip1 protein was below or at the threshold of
      detection in the differentiated cells of normal squamous epithelia from different
      body sites despite an up-regulation of p21cip1 RNA. In cervical intraepithelial
      neoplasias from patients who were also positive for the human immunodeficiency
      virus, there was an additional increase in p21cip1 RNA in the upper spinous cells
      without concomitant p21cip1 protein induction. A consistent inverse relationship
      was observed between the p21cip1 protein induction and abundant human
      papillomavirus DNA and RNAs. We propose that p21cip1 protein induction is a novel
      host response that inhibits viral DNA replication and thus prevents elevated
      viral transcription. This hypothesis can partly account for the heterogeneity and
      the differentiation-dependent viral activities commonly observed in benign human
      papillomavirus lesions.

PMID- 9546363
TI  - Insulinomas derived from hyperplastic intra-hepatic islet transplants.
AB  - Insulinomas were induced in a new animal model by transplanting a low number of
      isologous pancreatic islets via the portal vein into the livers of 66
      streptozotocin-induced diabetic rats. In contrast to high-number islet
      transplantation, which restored normoglycemia in 25 control animals, the low
      number islet transplantation was followed by persisting hyperglycemia for at
      least 13 months. Hyperplasia of islet cells developed in the transplanted islets
      as a consequence of hyperglycemia, which for the beta cells is not only a
      secretory but also a proliferative stimulus. Six of thirty-three animals between
      the 18th and the 24th month after islet transplantation changed from
      hyperglycemia to severe hypoglycemia, due to insulinomas that had developed in
      the liver from the transplanted islets. In contrast to other animal models,
      insulinoma development in this new model does not result from DNA damage by
      chemicals or radiation or from the expression of transgenes, but starts from
      apparently normal islets prepared from untreated isologous donors, which are
      exposed to an imbalance in glucose metabolism. The persistent proliferative
      stimulus and the metabolic alterations caused by the longstanding hyperglycemia
      seem to be the most relevant oncogenic factors in this model.

PMID- 9546364
TI  - The gamma-glutamyl transpeptidase gene is transcribed from a different promoter
      in rat hepatocytes and biliary cells.
AB  - Gamma-glutamyl transpeptidase (GGT) activity is commonly used to follow the
      differentiation of liver precursor cells into the biliary lineage. However, the
      GGT expression in immature hepatocytes or its induction in adult hepatocytes
      following diverse carcinogenic or noncarcinogenic treatments has questioned the
      reliability of GGT expression as a biliary marker. In the present study, we
      investigated the GGT gene expression from its five different promoters in the
      late fetal, neonatal, and adult rat liver by Northern blot, reverse transcription
      polymerase chain reaction, and in situ hybridization analysis. We show that the
      GGT activity in the 18-day-old fetus results from the transcription of the gene
      from the promoter P3 in the hepatocytes. In contrast, the GGT promoter P4
      activity appears to be specific of biliary cells in normal as well in cholestatic
      liver. Thus, sequences unique to the GGT transcripts initiated on these two
      alternate promoters provide unique molecular probes to discriminate between the
      biliary and the hepatocytic phenotypes in liver differentiation and cell lineage
      studies.

PMID- 9546366
TI  - Analysis and clinical implications of p53 gene mutations and human papillomavirus
      type 16 and 18 infection in primary adenocarcinoma of the uterine cervix.
AB  - Mutant p53 is frequently detected in endometrial and ovarian carcinoma, but it is
      rare in cervical cancers. Previous reports focused on cervical squamous cell
      carcinoma, whereas cervical adenocarcinoma was given little attention. We
      searched for p53 gene mutations in 74 primary cervical adenocarcinomas with known
      human papillomavirus (HPV) status. Our aim was to evaluate the prevalence of p53
      mutations and to investigate their possible role as an independent prognostic
      factor. We found mutations in 13.5% with a high rate of G:C --> A:T transitions
      as observed in endometrial adenocarcinoma. As p53 mutations are more frequently
      detected in malignancies of high grade, high stage, and large size, this
      molecular event seems to play a role in the progression rather than in the
      induction of cervical adenocarcinoma. In our series, patients with HPV-negative
      tumors and patients with mutated neoplasms, irrespective of HPV infection, had a
      shorter survival. Yet the absence of HPV infection and presence of p53 mutations
      are not independent risk factors for tumor-related death after adjustment for
      clinicopathological confounders. The only significant and independent predictors
      of survival are age of patient, stage of disease, tumor grade, and presence of
      lymph node metastases.

PMID- 9546365
TI  - Accelerated methylmercury elimination in gamma-glutamyl transpeptidase-deficient
      mice.
AB  - The disposition and toxicity of methylmercury, a ubiquitous environmental
      pollutant, is modulated by binding to the endogenous tripeptide glutathione (GSH)
      and metabolism of the resulting methylmercury-glutathione complex by the
      ectoproteins gamma-glutamyl transpeptidase (GGT) and dipeptidase. To evaluate the
      role of GGT in the whole-body disposition of methylmercury, we compared the
      elimination of [203Hg]methylmercury in GGT-deficient mice with that in wild-type
      mice and mice heterozygous for this deficiency. The effects of N-acetylcysteine
      (NAC), a drug used to maintain the cysteine and GSH levels of GGT-deficient mice,
      were also examined. Female mice were treated with either 0.5 or 25 micromol of
      CH3 203HgCl/kg body weight, in the presence and absence of 10 mg/ml NAC in the
      drinking water. There were no differences in methylmercury excretion between the
      wild-type and heterozygous mice; however, the GGT-deficient mice excreted
      methylmercury more rapidly at both dose levels. Wild-type and heterozygous mice
      excreted from 11 to 24% of the dose in the first 48 hours, whereas the GGT
      deficient mice excreted 55 to 66% of the dose, with most of the methylmercury
      being excreted in urine. Urinary methylmercury excretion was further accelerated
      in mice that received NAC. In contrast to methylmercury, the whole-body
      elimination of inorganic mercury was not affected by GGT deficiency, although the
      tissue distribution of inorganic mercury was markedly different in GGT-deficient
      male mice, with only 13% of the 203Hg body burden in the kidneys of GGT-deficient
      mice versus approximately 50% in kidneys of wild-type male mice. These findings
      provide direct evidence for a major role of GGT in regulating the tissue
      distribution and elimination of methylmercury and inorganic mercury and provide
      additional support for the use of NAC as an antidote in methylmercury poisoning.

PMID- 9546367
TI  - Monoclonality of both pale cells and cuboidal cells of sclerosing hemangioma of
      the lung.
AB  - Sclerosing hemangioma of the lung remains poorly understood, and it is still
      unclear whether this lesion is neoplastic or not. It consists of two major cell
      types, pale cells and cuboidal cells. We analyzed the clonality of each cell
      types from six female cases of surgically resected sclerosing hemangioma. The
      pale cells and cuboidal cells were separated by microdissection from methanol
      fixed sections, and DNA was extracted for clonal analysis based on an X
      chromosome-linked polymorphic marker, the human androgen receptor (HUMARA) gene
      or the phosphoglycerate kinase (PGK) gene. The HUMARA and PGK genes were found to
      be amplified with or without digestion by the methylation-sensitive restrictive
      endonuclease HpaII. Five of six cases were informative. Pale cells and cuboidal
      cells showed the same monoclonality in all of the informative cases, whereas the
      control cells showed a polyclonal pattern. Our results demonstrated that
      sclerosing hemangioma is caused by monoclonal expansion of cells, confirming that
      it is a neoplasia. Moreover, the present data indicate that both pale cells and
      cuboidal cells are derived from the same cell.

PMID- 9546368
TI  - Methylation alterations of the MyoD1 upstream region are predictive of
      subclassification of human rhabdomyosarcomas.
AB  - MyoD1 expression is a distinguishing characteristic of rhabdomyosarcoma. In this
      study, distinct methylation alterations were identified in the 5' flanking region
      of the MyoD1 gene from the two major subtypes, ie, alveolar and embryonal
      rhabdomyosarcoma. The MyoD1 methylation patterns of 26 rhabdomyosarcomas were
      compared with that of normal skeletal muscle and nonmuscle specimens by Southern
      blot analysis using methylation-sensitive restriction enzymes HhaI and HpaII. A 5
      kb region immediately upstream of the MyoD1 coding sequence was found to be
      methylated in adult muscle and all nonmuscle tissues tested. The MyoD1 upstream
      region was unmethylated in the majority of the alveolar rhabdomyosarcomas (13 of
      15, 87%) examined in this study. In contrast, 10 of 11 (91%) embryonal
      rhabdomyosarcomas showed a methylation pattern that was also observed in fetal
      muscle cells, in which the CpG sites in the MyoD1 upstream region were partially
      methylated. Our data suggest that the methylation status of the MyoD1 upstream
      CpG sites may be related to rhabdomyosarcoma tumorigenesis and may have valuable
      implications for its differential diagnosis.

PMID- 9546370
TI  - Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor
      suppressor gene.
AB  - Recent studies show that 1) the p53 tumor suppressor protein is overexpressed by
      rheumatoid arthritis (RA) synovium and fibroblast-like synoviocytes (FLS) and 2)
      somatic mutations previously identified in human tumors are present in RA
      synovium and FLS. We have hypothesized that abnormalities in p53 can contribute
      to chronic destructive RA synovitis. To understand the functional consequences of
      p53 abnormalities in FLS, RA and normal FLS expressing wild-type p53 were
      transduced with a retroviral vector encoding the human papilloma virus 18 E6
      gene, which inactivates endogenous p53 protein. Three RA and one normal FLS lines
      were infected with recombinant retrovirus encoding the neomycin resistance gene
      (neo) or E6+neo. FLS proliferation, apoptosis, and invasion was studied in E6,
      neo, and uninfected parental strains (PS). The growth rate for E6 was
      significantly increased with a sixfold increase in cell number after 7 days
      compared with a twofold to threefold increase in neo and PS. When FLS were
      treated with cytokines, proliferative response of E6, neo, and PS to interleukin
      1 and transforming growth factor-beta were similar. However, response to platelet
      derived growth factor was significantly greater in E6 FLS compared with neo or
      PS. Apoptosis was studied by incubating FLS with sodium nitroprusside as a source
      of nitric oxide or hydrogen peroxide for 8 hours and examining DNA fragmentation
      and E6 cells were significantly less susceptible to cell death. In addition, E6
      FLS were more invasive into cartilage extracts than neo or PS using an in vitro
      cell invasion assay. These data suggest that p53 is a critical regulator of FLS
      proliferation, apoptosis, and invasiveness. Abnormalities of p53 function might
      contribute to synovial lining expansion and joint destruction in RA.

PMID- 9546371
TI  - A rat model of spontaneous myopathy and malignant hyperthermia.
AB  - Malignant hyperthermia is a main cause of death during general anesthesia,
      particularly in children. However, research has been hampered by the lack of a
      convenient animal model, the only one available being a special strain of pig. In
      this study, we describe spontaneous myopathy and a fatal syndrome of generalized
      muscle rigidity triggered by halothane in an outbred strain of rat. Histological
      examination of skeletal muscle reveals severe abnormalities indicating chronic
      underlying myopathy. The association of histological abnormalities with an acute,
      fatal syndrome clinically resembling malignant hyperthermia provides a strong
      basis for a new and extremely useful animal model to study this fatal disorder.

PMID- 9546369
TI  - Heterogeneity in Lewis-X and sialyl-Lewis-X antigen expression on monocytes in
      whole blood: relation to stimulus-induced oxidative burst.
AB  - By using flow cytometric analysis of cells in whole blood expressing high levels
      of CD14, we found a subpopulation of monocytes (8% of total) with higher scatter
      parameters, high capacity to produce reactive oxygen species (ROS), stronger
      expression of Lewis-X (CD15), sialyl-Lewis-X, CD11b and CD18 antigens, as well as
      an increased polymerized actin content. The size of this subpopulation increased
      after stimulation with lipopolysaccharide at the expense of the remaining
      monocytes, suggesting that its features were inducible. The membrane increase in
      Lewis-X and sialyl-Lewis-X expression observed during this conversion was largely
      due to the translocation of these carbohydrate structures from intracellular
      pools. Moreover, this subpopulation behaved as a primed monocyte subpopulation
      producing large amounts of H2O2 in response to N-formyl-methionyl-leucyl
      phenylalanine. Increased H2O2 production was inhibited not only by anti-CD14 but
      also by anti-CD15 and anti-sialyl-Lewis-X monoclonal antibodies when added before
      lipopolysaccharide. These results show that lipopolysaccharide priming is
      regulated, at least in part, by Lewis-X and sialyl-Lewis-X structures expressed
      on the monocyte membrane. All together, this highly reactive and inducible
      subpopulation of monocytes, which share phenotypic and functional characteristics
      with neutrophils, might play an important role in host defenses and inflammatory
      responses.

PMID- 9546372
TI  - Development of the cardiac conduction system.

PMID- 9546373
TI  - Formation of the atrioventricular septal structures in the normal mouse.
AB  - It is sometimes thought that formation of the atrioventricular septum is equated
      with fusion of the endocardial cushions and that failure of fusion can explain
      all deficiencies of atrioventricular septation. Clearly, this is simplistic, but
      the exact contribution of different primordia to atrioventricular septation is
      not well understood. To clarify this, we studied normal mouse embryos (days 10 to
      15 of gestation), which were serially sectioned and examined by light microscopy.
      Another group of embryos was examined by scanning electron microscopy after
      microdissection. Our results show that development of the atrioventricular septal
      area is highly complex. Proper formation requires the following: remodeling of
      the inner heart curvature, rotation of the horns of the systemic venous sinus
      around the pulmonary portal, expansion of the right atrioventricular junction,
      formation of the muscular atrial and ventricular septa, bridging by the
      dextrodorsal outflow ridge and the superior endocardial cushion, fusion with the
      inferior margins of the venous valves, and formation of the mouth of the coronary
      sinus from the cranial muscular wall of the left sinus horn. Multiple primordia
      contribute to a central mesenchymal mass (the "septum intermedium"), including
      the mesenchyme on the leading edge of the primary atrial septum, the
      atrioventricular endocardial cushions, and the cap of mesenchyme on the spina
      vestibuli. Fusion of these components closes the ostium primum, completing atrial
      and atrioventricular septation. Additionally, the spina vestibuli has a
      mesodermal core, which contributes to the muscularization of the lower margin of
      the oval fossa. This contrasts with the formation of the upper rim, which occurs
      as a result of an infolding of the atrial wall itself.

PMID- 9546374
TI  - Effects of overexpression of the Na+-Ca2+ exchanger on [Ca2+]i transients in
      murine ventricular myocytes.
AB  - We measured [Ca2+]i and [Na+]i in isolated transgenic (TG) mouse myocytes
      overexpressing the Na+-Ca2+ exchanger and in wild-type (WT) myocytes. In TG
      myocytes, the peak systolic level and amplitude of electrically stimulated (ES)
      [Ca2+]i transients (0.25 Hz) were not significantly different from those in WT
      myocytes, but the time to peak [Ca2+]i was significantly prolonged. The decline
      of ES [Ca2+]i transients was significantly accelerated in TG myocytes. The
      decline of a long-duration (4-s) caffeine-induced [Ca2+]i transient was markedly
      faster in TG myocytes, and [Na+]i was identical in TG and WT myocytes, indicating
      that the overexpressed Na+-Ca2+ exchanger is functionally active. The decline of
      a short-duration (100-ms) caffeine-induced [Ca2+]i transient in 0 Na+/0 Ca2+
      solution did not differ between the two groups, suggesting that the sarcoplasmic
      reticulum (SR) Ca2+-ATPase function is not altered by overexpression of the Na+
      Ca2+ exchanger. There was no difference in L-type Ca2+ current density in WT and
      TG myocytes. However, the sensitivity of ES [Ca2+]i transients to nifedipine was
      reduced in TG myocytes. This maintenance of [Ca2+]i transients in nifedipine was
      inhibited by Ni2+ and required SR Ca2+ content, consistent with enhanced Ca2+
      influx by reverse Na+-Ca2+ exchange, and the resulting Ca2+-induced Ca2+ release
      from SR. The rate of rise of [Ca2+]i transients in nifedipine in TG myocytes was
      much slower than when both the L-type Ca2+ current and the Na+-Ca2+ exchange
      current function together. In TG myocytes, action potential amplitude and action
      potential duration at 50% repolarization were reduced, and action potential
      duration at 90% repolarization was increased, relative to WT myocytes. These data
      suggest that under these conditions, overexpression of the Na+-Ca2+ exchanger in
      TG myocytes accelerates the decline of [Ca2+]i during relaxation, indicating
      enhanced forward Na+-Ca2+ exchanger function. Increased Ca2+ influx also appears
      to occur, consistent with enhanced reverse function. These findings provide
      support for the physiological importance of both these modes of Na+-Ca2+
      exchange.

PMID- 9546375
TI  - Angiotensin II activates RhoA in cardiac myocytes: a critical role of RhoA in
      angiotensin II-induced premyofibril formation.
AB  - The organization of actin into striated fibers (myofibrils) is one of the major
      features of cardiac hypertrophy. However, its signal transduction mechanism is
      not well understood. Although Rho-family small G proteins have been implicated in
      actin organization in many cell types, it is not fully elucidated whether Rho
      mediates the organization of actin fibers by hypertrophic stimuli in cardiac
      myocytes. Therefore, we examined (1) whether Rho is activated by the hypertrophic
      stimulus, angiotensin II (Ang II), and (2) whether Rho mediates the Ang II
      induced organization of actin fibers in cultured neonatal rat cardiac myocytes.
      Treatment of myocytes with Ang II caused a rapid formation of both striated
      (mature myofibrils) and nonstriated (premyofibrils) actin fibers within 30
      minutes, as determined by phalloidin stainings of the polymerized actin and
      troponin T stainings. Immunoblot analyses and immunostainings have indicated that
      cardiac myocytes express RhoA, but RhoB is undetectable. In the control state,
      RhoA was observed predominantly in the cytosolic fraction, but it was
      translocated in part to the particulate fraction in response to Ang II,
      consistent with activation of RhoA by Ang II. Incubation of myocytes with
      exoenzyme C3 for 48 hours completely ADP-ribosylated Rho in vivo. The C3
      treatment abolished formation of premyofibrils induced by Ang II, suggesting that
      Ang II causes premyofibril formation via a Rho-dependent mechanism. The Ang II
      induced mature myofibril formation was only partly abolished by C3. Expression of
      constitutively active RhoA (V14RhoA) caused the formation of premyofibrils but
      not mature myofibrils. The C3 treatment inhibited Ang II-induced atrial
      natriuretic factor induction, whereas it had no effect on c-fos induction. These
      results indicate that RhoA is activated by Ang II and mediates the Ang II-induced
      formation of premyofibrils and induction of a subset of genes. Distinct signaling
      mechanisms seem to be responsible for striated mature myofibril formation by Ang
      II.

PMID- 9546376
TI  - Acute glucose overload abolishes Ca2+ oscillation in cultured endothelial cells
      from bovine aorta: a possible role of superoxide anion.
AB  - Effects of acute glucose overload on [Ca2+]i were investigated in cultured
      endothelial cells from bovine aorta. Application of 0.1 micromol/L ATP elicited
      an oscillatory increase in [Ca2+]i (Ca2+ oscillation) in Krebs solution
      containing 11.5 mmol/L glucose. The frequency of Ca2+ oscillation induced by ATP
      increased in a concentration-dependent manner, ranging between 0.03 and 1
      micromol/L. When cells were preincubated with 23 mmol/L glucose-containing Krebs
      solution (high glucose solution) for 3 hours, 0.1 micromol/L ATP failed to induce
      Ca2+ oscillation but evoked only a phasic followed by sustained increase in
      [Ca2+]i. Application of a higher concentration of ATP (10 micromol/L) evoked a
      transient increase in [Ca2+]i both in control and high glucose-treated cells.
      However, the falling phase of [Ca2+]i was prolonged in high glucose-treated
      cells. Thapsigargin (1 micromol/L), an inhibitor of endoplasmic Ca2+-ATPase,
      induced a transient followed by a sustained increase in [Ca2+]i in control cells.
      Preincubation with high glucose solution increased the rate of rise of the
      thapsigargin-induced increase in [Ca2+]i and abolished the sustained increase,
      suggesting that glucose overload accelerates Ca2+ leak from intracellular store
      sites and impairs Ca2+ release-activated Ca2+ entry. We found that all of the
      glucose overload-induced changes in Ca2+ mobilization could be mimicked by
      xanthine with xanthine oxidase and abolished by superoxide dismutase. These
      results indicate that acute glucose overload accumulates superoxide anion in
      bovine aortic endothelial cells, thereby diminishing ATP-induced Ca2+ oscillation
      through the impairment of Ca2+ homeostasis.

PMID- 9546377
TI  - Ca2+-independent activation of the endothelial nitric oxide synthase in response
      to tyrosine phosphatase inhibitors and fluid shear stress.
AB  - Fluid shear stress enhances NO formation via a Ca2+-independent tyrosine kinase
      inhibitor-sensitive pathway. In the present study, we investigated the effects of
      the protein tyrosine phosphatase inhibitor phenylarsine oxide and of fluid shear
      stress on endothelial NO production as well as on the membrane association and
      phosphorylation of the NO synthase (NOS) III. Phenylarsine oxide (10 micromol/L)
      induced an immediate and maintained NO-mediated relaxation of isolated rabbit
      carotid arteries, which was insensitive to the removal of extracellular Ca2+ and
      the calmodulin antagonist calmidazolium. This phenylarsine oxide-induced
      vasodilatation was unaffected by genistein but abrogated by the tyrosine kinase
      inhibitor erbstatin A. Incubation of native or cultured endothelial cells with
      phenylarsine oxide resulted in a time-dependent tyrosine phosphorylation of
      mainly Triton X-100-insoluble (cytoskeletal) proteins, along with a parallel
      change in the detergent solubility of NOS III, such that the enzyme was recovered
      in the cytoskeletal fraction. A similar, though slightly delayed, phenomenon was
      also observed after the application of fluid shear stress but not in response to
      any receptor-dependent agonist. Although Ca2+-independent NO formation was
      sensitive to erbstatin A, phenylarsine oxide treatment was associated with the
      tyrosine dephosphorylation of NOS III rather than its hyperphosphorylation.
      Proteins that also underwent redistribution in response to the tyrosine
      phosphatase inhibitor included paxillin, phospholipase C-gamma1, mitogen
      activated protein kinase, and the tyrosine kinases Src and Fyn. We envisage that
      fluid shear stress and tyrosine phosphatase inhibitors may alter the conformation
      and/or protein coupling of NOS III, facilitating its interaction with specific
      phospholipids, proteins, and/or protein kinases that enhance/maintain its Ca2+
      independent activation.

PMID- 9546378
TI  - Pulsatile stretch in coronary arteries elicits release of endothelium-derived
      hyperpolarizing factor: a modulator of arterial compliance.
AB  - To date, the release of the endothelium-derived hyperpolarizing factor (EDHF) has
      been demonstrated only in response to receptor-dependent Ca2+-elevating agonists.
      Since endothelial cells in situ are continuously subjected to rhythmic
      distension, we investigated the effect of rhythmic stretch on the release of EDHF
      from isolated porcine coronary arteries. In the combined presence of diclofenac
      and N(G)-nitro-L-arginine (L-NNA), sinusoidal pressure oscillations (from 40 to
      50 mm Hg, 4 minutes, 1.5 Hz) led to simultaneous oscillations in the external
      diameter of coronary artery segments, the amplitude of which were decreased by
      iberiotoxin and apamin and also by endothelial denudation. In order to directly
      demonstrate the release of EDHF, the intraluminal solution from endothelium
      intact coronary segments exposed to pulsatile stretch was applied to detector rat
      aortic smooth muscle cells, the membrane potential of which was continuously
      measured using the patch-clamp technique. The hyperpolarization of detector cells
      induced by the intraluminal solution was proportional to the amplitude of the
      pressure oscillations applied to the donor artery and was attenuated by either
      preincubation of donor arteries with 17-octadecynoic acid or application of
      either tetrabutylammonium or iberiotoxin to detector cells. In contrast to the
      bradykinin-induced release of EDHF, the EDHF synthesized in response to pulsatile
      stretch did not exhibit any tachyphylaxis. These findings demonstrate for the
      first time that the synthesis of EDHF in coronary arteries can be mechanically
      stimulated by rhythmic vessel wall distension and suggest that the continuous
      release of EDHF may contribute to the adjustment of an adequate vascular
      compliance and to the control of coronary blood flow.

PMID- 9546379
TI  - Cooperative interactions between RB and p53 regulate cell proliferation, cell
      senescence, and apoptosis in human vascular smooth muscle cells from
      atherosclerotic plaques.
AB  - Compared with vascular smooth muscle cells (VSMCs) from normal vessels, VSMCs
      from human atherosclerotic plaques proliferate more slowly, undergo earlier
      senescence, and demonstrate higher levels of apoptosis in culture. The tumor
      suppressor genes p105RB (retinoblastoma, acting through the E2F transcription
      factor family) and p53 regulate cell proliferation, cell senescence, and
      apoptosis in many cell types. We have therefore determined whether these stable
      growth properties of plaque VSMCs reflect altered activity of RB and/or p53.
      VSMCs were derived from coronary atherectomies or from normal coronary arteries
      from transplant recipients. Compared with normal VSMCs, plaque VSMCs showed a
      higher ratio of the active (hypophosphorylated) to the inactive (phosphorylated)
      form of RB and a lower level of E2F transcriptional activity. Cells were stably
      transfected with retrovirus constructs that inhibited RB or p53 alone or in
      combination. Suppression of RB alone increased rates of cell proliferation and
      apoptosis and inhibited cell senescence in normal VSMCs. Suppression of p53 and
      RB together had similar effects but, additionally, resulted in immortalization of
      normal VSMC cultures. In contrast, inhibition of RB binding to E2F or ectopic
      expression of E2F-1 in plaque VSMCs induced massive apoptosis, which required
      suppression of p53 to rescue cells. Suppression of RB and p53 together increased
      cell proliferation and delayed senescence but failed to immortalize plaque VSMCs.
      Inhibition of p53 alone had minimal effects on plaque VSMCs but increased the
      lifespan of normal VSMCs. We conclude that human plaque VSMCs have slower rates
      of cell proliferation and earlier senescence than do cells from normal vessels
      because of a defect in phosphorylation of RB. Furthermore, both disruption of
      RB/E2F and inhibition of p53 are required for plaque VSMCs to proliferate without
      apoptosis. This observation may explain the relatively low level of cell
      proliferation and high level of apoptosis seen in VSMCs in human atherosclerotic
      plaques.

PMID- 9546381
TI  - Response of intra-acinar pulmonary microvessels to hypoxia, hypercapnic acidosis,
      and isocapnic acidosis.
AB  - To elucidate the differential reactivity of pulmonary microvessels in the acini
      to hypoxia, excessive CO2, and increased H+, we investigated changes in the
      diameter of precapillary arterioles, postcapillary venules, and capillaries in
      isolated rat lungs on exposure to normocapnic hypoxia (2% O2), normoxic
      hypercapnia (15% CO2), and isocapnic acidosis (0.01 mol/L HCl). Microvascular
      diameters were precisely examined using a real-time confocal laser scanning
      luminescence microscope coupled to a high-sensitivity camera with an image
      intensifier. Measurements were made under conditions with and without
      indomethacin or N(omega)-nitro-L-arginine methyl ester to assess the importance
      of vasoactive substances produced by cyclooxygenase (COX) or NO synthase (NOS) as
      it relates to the reactivity of pulmonary microvessels to physiological stimuli.
      We found that acute hypoxia contracted precapillary arterioles that had diameters
      of 20 to 30 microm but did not constrict postcapillary venules of similar size.
      COX- and NOS-related vasoactive substances did not modulate hypoxia-elicited
      arteriolar constriction. Hypercapnia induced a distinct venular dilatation
      closely associated with vasodilators produced by COX but not by NOS. Arterioles
      were appreciably constricted in isocapnic acidosis when NOS, but not COX, was
      suppressed, whereas venules showed no constrictive response even when both
      enzymes were inhibited. Capillaries were neither constricted nor dilated under
      any experimental conditions. These findings suggest that reactivity to hypoxia,
      CO2, and H+ is not qualitatively similar among intra-acinar microvessels, in
      which COX- and NOS-associated vasoactive substances function differently.

PMID- 9546380
TI  - Cell replication in the arterial wall: activation of signaling pathway following
      in vivo injury.
AB  - This study examined intracellular signal events of arterial cells following
      balloon catheter injury to rat carotid artery. Within 30 minutes, a marked
      increase in extracellular signal-regulated kinase-1/2 (ERK1/2) activity was
      observed. This activity remained elevated for 12 hours but had decreased to
      control levels by day 1. No increase in ERK1/2 was detected at any later times.
      Injection of anti-fibroblast growth factor 2 antibody (60 mg i.v.) significantly
      inhibited the activation of ERK1/2 at 30 minutes after the injury. PD98059 (80
      micromol/L), a selective inhibitor of mitogen-activated protein kinase/ERK kinase
      1 (MEK1), decreased ERK1/2 activity in injured arteries and also reduced the
      medial cell replication. In contrast, PD98059 did not block the intimal cell
      replication at day 8. Mitogen-activated protein kinase phosphatase-1 (MKP-1) was
      expressed within hours after injury but only weakly at later times; MKP-1 was
      again expressed after 7 and 14 days. The expression of MKP-1 was associated with
      an activation of c-Jun amino-terminal kinase. Injury to the arterial wall also
      stimulated the activity of p70 S6 kinase from 30 minutes to 12 hours, suggesting
      an alternative pathway in mitogenic signaling of early cell replication. These
      findings demonstrate that fibroblast growth factor 2-induced ERK1/2 activation
      promotes medial cell replication after balloon injury; however, signaling of
      intimal cell replication may not be linked to the MEK1-dependent ERK pathway.

PMID- 9546382
TI  - Increased expression of Ca2+-sensitive K+ channels in the cerebral
      microcirculation of genetically hypertensive rats: evidence for their protection
      against cerebral vasospasm.
AB  - The Ca2+-sensitive K+ channel (K(Ca) channel) plays a key role in buffering
      pressure-induced constriction of small cerebral arteries. An amplified current
      through this channel has been reported in vascular smooth muscle cells obtained
      from hypertensive animals, implying that the expression or properties of K(Ca)
      channels may be regulated by in vivo blood pressure levels. In this study, we
      investigated this hypothesis and its functional relevance by comparing the
      properties, expression levels, and physiological role of K(Ca) channels in
      cerebral resistance arteries from normotensive and genetically hypertensive rats.
      Whole-cell patch-clamp experiments revealed a 4.7-fold higher density of
      iberiotoxin-sensitive K(Ca) channel current at physiological membrane potentials
      in spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKY) rat
      cerebrovascular smooth muscle cells (n = 18 and 21, respectively). However,
      additional single-channel analysis in detached patches showed similar levels of
      unitary conductance, voltage, and Ca2+ sensitivity in K(Ca) channels from WKY and
      from SHR membranes. In contrast, Western analysis using an antibody directed
      against the K(Ca) channel alpha-subunit revealed a 4.1-fold increase in the
      corresponding 125-kD immunoreactive signal in cerebrovascular membranes from SHR
      compared with WKY rats. The functional impact of this enhanced K(Ca) channel
      expression was assessed in SHR and WKY rat pial arterioles, which were monitored
      by intravital microscopy through in situ cranial windows. Progressive
      pharmacological block of K(Ca) channels by iberiotoxin (0.1 to 100 nmol/L) dose
      dependently constricted pial arterioles from SHR and WKY rats (n = 6 to 8). The
      arterioles in SHR constricted 2- to 4-fold more intensely, and vasospasm occurred
      in some vessels. These data provide the first direct evidence that elevated
      levels of in situ blood pressure induce K(Ca) channel expression in
      cerebrovascular smooth muscle membranes. This homeostatic mechanism may
      critically regulate the resting tone of cerebral arterioles during chronic
      hypertension. Furthermore, the overexpression of distinct K+ channel types during
      specific cardiovascular pathologies may provide for the upregulation of novel
      disease-specific membrane targets for vasodilator therapies.

PMID- 9546383
TI  - Wag the tail: structural dynamics of actomyosin.

PMID- 9546384
TI  - Kinesin: what gives?

PMID- 9546386
TI  - RNA polymerase as a molecular motor.

PMID- 9546385
TI  - Staying on track: common features of DNA helicases and microtubule motors.

PMID- 9546387
TI  - The turn of the screw: the bacterial flagellar motor.

PMID- 9546388
TI  - F1-ATPase: a rotary motor made of a single molecule.

PMID- 9546389
TI  - The transfer of left-right positional information during chick embryogenesis.
AB  - The earliest known left-right asymmetric genes are expressed at Hensen's node
      during chick gastrulation. Gene expression following reorientation of the node
      shows asymmetry is instructed by adjacent tissue, hence left-right information
      originates outside the node. Subsequently, the node signals back to the lateral
      tissue, initiating a cascade leading to left-sided expression of nodal in the
      lateral plate mesoderm. Loss of nodal expression in the presence of blocking
      antibodies confirms that Sonic hedgehog is the key signal conveying left-right
      information from the node; however, manipulation of explant cultures suggests
      that the induction of nodal requires secondary signals produced in the paraxial
      mesoderm. These experiments establish the time of action of these signals to and
      from Hensen's node in establishing left-right asymmetry.

PMID- 9546390
TI  - The left-right coordinator: the role of Vg1 in organizing left-right axis
      formation.
AB  - The asymmetries of internal organs are consistently oriented along the left-right
      axis in all vertebrates, and perturbations of left-right orientation lead to
      significant congenital disease. We propose a model in which a "left-right
      coordinator" interacts with the Spemann organizer to coordinate the
      evolutionarily conserved three-dimensional asymmetries in the embryo. The Vg1
      cell-signaling pathway plays a central role in left-right coordinator function.
      Antagonists of Vg1 alter left-right development; antagonists of other members of
      the TGFbeta family do not. Cell-lineage directed expression of Vg1 protein can
      fully invert the left-right axis (situs inversus), can randomize left-right
      asymmetries, or can "rescue" a perturbed left-right axis in conjoined twins to
      normal orientation (situs solitus), indicating that Vg1 can mimic left-right
      coordinator activity. These are the first molecular manipulations in any
      vertebrate by which the left-right axis can be reliably controlled.

PMID- 9546391
TI  - Odorant receptors govern the formation of a precise topographic map.
AB  - Olfactory neurons expressing a given odorant receptor project with precision to 2
      of the 1800 glomeruli within the olfactory bulb to create a topographic map of
      odor quality. We demonstrate that deletions or nonsense mutations in the P2
      odorant receptor gene cause the axons of these cells to wander rather than
      converge on a specific glomerulus. Receptor substitution experiments that replace
      the P2 gene with the coding region of the P3 gene result in the projection of P3-
      >P2 axons to a glomerulus touching the wild-type P3 glomerulus. These data, along
      with additional receptor substitutions, indicate that the odorant receptor plays
      an instructive role in the establishment of the topographic map.

PMID- 9546392
TI  - Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause
      combined deficiency of coagulation factors V and VIII.
AB  - Combined deficiency of factors V and VIII is an autosomal recessive bleeding
      disorder resulting from alterations in an unknown gene on chromosome 18q,
      distinct from the factor V and factor VIII genes. ERGIC-53, a component of the ER
      Golgi intermediate compartment, was mapped to a YAC and BAC contig containing the
      critical region for the combined factors V and VIII deficiency gene. DNA sequence
      analysis identified two different mutations, accounting for all affected
      individuals in nine families studied. Immunofluorescence and Western analysis of
      immortalized lymphocytes from patients homozygous for either of the two mutations
      demonstrate complete lack of expression of the mutated gene in these cells. These
      findings suggest that ERGIC-53 may function as a molecular chaperone for the
      transport from ER to Golgi of a specific subset of secreted proteins, including
      coagulation factors V and VIII.

PMID- 9546393
TI  - The C. elegans spe-9 gene encodes a sperm transmembrane protein that contains EGF
      like repeats and is required for fertilization.
AB  - In the nematode worm C. elegans, individuals with mutations in the spe-9 gene
      produce spermatozoa with wild-type morphology and motility that cannot fertilize
      oocytes even after contact between gametes. Therefore, disruption of spe-9
      function affects either gamete recognition, adhesion, signaling, and/or fusion.
      The spe-9 gene encodes a sperm transmembrane protein with an extracellular domain
      that contains ten epidermal growth factor-like repeats. A common feature of
      proteins that include epidermal growth factor-like motifs is their involvement in
      extracellular functions such as adhesive and ligand-receptor interactions.
      Additionally, the overall structure of the predicted SPE-9 protein is similar to
      that of ligands for the Notch/LIN-12/GLP-1 family of transmembrane receptors.
      These results suggest that SPE-9 functions in the specialized cell-cell
      interactions required for fertilization.

PMID- 9546394
TI  - Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic
      checkpoint protein MAD1.
AB  - In searching for cellular targets of the HTLV-I oncoprotein Tax, we identified
      TXBP181, which we characterized as the human homolog of yeast mitotic checkpoint
      MAD1 protein. Evidence supporting TXBP181 as HsMAD1 includes sequence
      conservation with yeast MAD1, hyperphosphorylation during S/G2/M phases and upon
      treatment of cells with nocodazole, and binding to HsMAD2. HsMAD1 functions as a
      homodimer. It localizes to the centrosome during metaphase and to the spindle
      midzone and the midbody during anaphase and telophase. Expression of either Tax
      or a transdominant-negative TXBP181 results in multinucleated cells, a phenotype
      consistent with a loss of HsMAD1 function. We propose a model of viral
      transformation in which Tax targets TXBP181, thereby abrogating a mitotic
      checkpoint.

PMID- 9546395
TI  - A novel and ubiquitous system for membrane targeting and secretion of cofactor
      containing proteins.
AB  - We report the identification of the proteins encoded by the mttABC operon
      (formerly yigTUW), which mediate a novel Sec-independent membrane targeting and
      translocation system in Escherichia coli that interacts with cofactor-containing
      redox proteins having a S/TRRXFLK "twin arginine" leader motif. A pleiotropic
      negative mutant in mttA prevents the periplasmic localization of twin arginine
      redox enzymes, including nitrate reductase (NapA) and trimethylamine N-oxide
      reductase (TorA). The mutation also prevents the correct localization of the
      integral membrane molybdoenzyme dimethylsulfoxide reductase (DmsABC). The DmsA
      subunit has a twin arginine leader. Proteins with a Sec-dependent leader or which
      assemble spontaneously in the membrane are not affected by this mutation. MttA,
      B, and C are members of a large family of related sequences extending from
      archaebacteria to higher eukaryotes.

PMID- 9546396
TI  - The unusual active site of Gal6/bleomycin hydrolase can act as a
      carboxypeptidase, aminopeptidase, and peptide ligase.
AB  - The Gal6 protease is in a class of cysteine peptidases identified by their
      ability to inactivate the anti-cancer drug bleomycin. The protein forms a barrel
      structure with the active sites embedded in a channel as in the proteasome. In
      Gal6 the C termini lie in the active site clefts. We show that Gal6 acts as a
      carboxypeptidase on its C terminus to convert itself to an aminopeptidase and
      peptide ligase. The substrate specificity of the peptidase activity is determined
      by the position of the C terminus of Gal6 rather than the sequence of the
      substrate. We propose a model to explain these diverse activities and Gal6's
      singular ability to inactivate bleomycin.

PMID- 9546397
TI  - Crystal structure of the hemochromatosis protein HFE and characterization of its
      interaction with transferrin receptor.
AB  - HFE is an MHC-related protein that is mutated in the iron-overload disease
      hereditary hemochromatosis. HFE binds to transferrin receptor (TfR) and reduces
      its affinity for iron-loaded transferrin, implicating HFE in iron metabolism. The
      2.6 A crystal structure of HFE reveals the locations of hemochromatosis mutations
      and a patch of histidines that could be involved in pH-dependent interactions. We
      also demonstrate that soluble TfR and HFE bind tightly at the basic pH of the
      cell surface, but not at the acidic pH of intracellular vesicles. TfR:HFE
      stoichiometry (2:1) differs from TfR:transferrin stoichiometry (2:2), implying a
      different mode of binding for HFE and transferrin to TfR, consistent with our
      demonstration that HFE, transferrin, and TfR form a ternary complex.

PMID- 9546398
TI  - Crystal structure of the thermosome, the archaeal chaperonin and homolog of CCT.
AB  - We have determined to 2.6 A resolution the crystal structure of the thermosome,
      the archaeal group II chaperonin from T. acidophilum. The hexadecameric homolog
      of the eukaryotic chaperonin CCT/TRiC shows an (alphabeta)4(alphabeta)4 subunit
      assembly. Domain folds are homologous to GroEL but form a novel type of inter
      ring contact. The domain arrangement resembles the GroEL-GroES cis-ring. Parts of
      the apical domains form a lid creating a closed conformation. The lid substitutes
      for a GroES-like cochaperonin that is absent in the CCT/TRiC system. The central
      cavity has a polar surface implicated in protein folding. Binding of the
      transition state analog Mg-ADP-AIF3 suggests that the closed conformation
      corresponds to the ATP form.

PMID- 9546399
TI  - Human Tra2 proteins are sequence-specific activators of pre-mRNA splicing.
AB  - The RNA-binding protein Tra2 is an important regulator of sex determination in
      Drosophila. Recently, two mammalian Tra2 homologs of unknown function have been
      described. Here, we show that human Tra2 proteins are present in HeLa cell
      nuclear extracts and that they bind efficiently and specifically to a previously
      characterized pre-mRNA splicing enhancer element. Indeed, both purified proteins
      bound preferentially to RNA sequences containing GAA repeats, characteristic of
      many enhancer elements. Neither Tra2 protein functioned in constitutive splicing
      in vitro, but both activated enhancer-dependent splicing in a sequence-specific
      manner and restored it after inhibition with competitor RNA. Our findings
      indicate that mammalian Tra2 proteins are sequence-specific splicing activators
      that likely participate in the control of cell-specific splicing patterns.

PMID- 9546400
TI  - Receptor-specific adhesion and clinical disease in Plasmodium falciparum.

PMID- 9546401
TI  - A geographic information system applied to a malaria field study in western
      Kenya.
AB  - This paper describes use of the global positioning system (GPS) in differential
      mode (DGPS) to obtain highly accurate longitudes, latitudes, and altitudes of
      1,169 houses, 15 schools, 40 churches, four health care centers, 48 major
      mosquito breeding sites, 10 borehole wells, seven shopping areas, major roads,
      streams, the shore of Lake Victoria, and other geographic features of interest
      associated with a longitudinal study of malaria in 15 villages in western Kenya.
      The area mapped encompassed approximately 70 km2 and included 42.0 km of roads,
      54.3 km of streams, and 15.0 km of lake shore. Location data were entered into a
      geographic information system for map production and linkage with various
      databases for spatial analyses. Spatial analyses using parasitologic and
      entomologic data are presented as examples. Background information on DGPS is
      presented along with estimates of effort and expense to produce the map
      information.

PMID- 9546402
TI  - The historical question of acquired immunodeficiency syndrome in the 1960s in the
      Congo River basin area in relation to cryptococcal meningitis.
AB  - In Europe before the advent of the acquired immunodeficiency syndrome (AIDS),
      fatal cases of infection with Cryptococcus neoformans resembling acute meningitis
      were rarely described and never in young adults. However, rapidly fatal
      cryptococcal meningitis in young Africans has been known to exist in central
      Africa for at least 30 years, mainly in the lower area of the Congo River basin.
      Cases have been reported in this area since 1953, particularly in young patients
      during the 1950s. It is also known that central African AIDS patients frequently
      suffer from cryptococcosis, and there is a possibility that earlier clinical
      reports of encephalitis were actually fatal cases of AIDS in young Africans. It
      appears possible that the central part of the African continent is the area where
      human immunodeficiency virus originated.

PMID- 9546403
TI  - Aedes aegypti survival and dispersal estimated by mark-release-recapture in
      northern Australia.
AB  - The survival and dispersal of adult Aedes aegypti were estimated in northern
      Australia where sporadic outbreaks of Ae. aegypti-borne dengue viruses have
      occurred in recent years. Standard mark-release-recapture methods were used. In
      addition, a new sticky trap was used to capture the mosquitoes. Prior to the
      field study, the survival and effect of marking Ae. aegypti with fluorescent
      powder were determined in the laboratory. Mortality was age-dependent and the
      marked cohorts had higher survival rates than the untreated cohorts. Recapture
      rates of 13.0% and 3.6% over a seven-day period were achieved for two batches of
      marked Ae. aegypti released simultaneously at the field site. More males than
      females were recaptured although the proportion of females increased with time.
      The probability of daily survival was 0.91 and 0.86 for the blue- and pink-marked
      females, respectively, and 0.57 and 0.70 for the blue- and pink-marked and males,
      respectively. The mean distance traveled of recaptured Ae. aegypti was 56 m and
      35 m for females and males, respectively. The maximum observed distance traveled
      of 160 m was the same for both sexes. The warm to hot and dry climatic conditions
      may have restricted the dispersal of released mosquitoes in this study. The
      frequency of recaptures at certain trap locations suggested that shade, wind, and
      the availability of hosts affected the distribution of Ae. aegypti within the
      study site.

PMID- 9546404
TI  - Effect of size and geographic origin of Aedes aegypti on oral infection with
      dengue-2 virus.
AB  - Differences in larval habitats cause variation in the size of Aedes aegypti (L.)
      adults. We suspected that such size variation was related to the ease with which
      the mosquitoes could be infected with dengue virus. Using a rearing procedure
      that produced three distinct size classes of mosquitoes, we determined the
      percentage of mosquitoes that developed disseminated dengue-2 infection following
      oral feeding with a suspension containing 3.3 x 10(7) plaque-forming units/ml.
      Mosquitoes were reared from eggs deposited by females captured in either of two
      villages in Chachoengsao Province or in Bangkok, Thailand. More of the larger
      mosquitoes (10.7%) were infected than the medium (5.6%) or small (5.7%)
      mosquitoes. Mosquitoes from Bangkok were less easily infected (5.0%) than
      mosquitoes from either of the two villages (8.5% and 10.7%). These results
      suggest that quantitative risk assessment of dengue transmission may be very
      difficult unless inoculation rate is measured directly. Also, control procedures
      that reduce density of larvae in individual containers may exacerbate dengue
      transmission by creating larger mosquitoes that are more easily infected.

PMID- 9546405
TI  - Exploratory space-time analysis of reported dengue cases during an outbreak in
      Florida, Puerto Rico, 1991-1992.
AB  - The spatial and temporal distributions of dengue cases reported during a 1991
      1992 outbreak in Florida, Puerto Rico (population = 8,689), were studied by using
      a Geographic Information System. A total of 377 dengue cases were identified from
      a laboratory-based dengue surveillance system and georeferenced by their
      residential addresses on digital zoning and U.S. Geological Survey topographic
      maps. Weekly case maps were generated for the period between June and December
      1991, when 94.2% of the dengue cases were reported. The temporal evolution of the
      epidemic was rapid, affecting a wide geographic area within seven weeks of the
      first reported cases of the season. Dengue cases were reported in 217 houses; of
      these 56 (25.8%) had between two and six reported cases. K-function analysis was
      used to characterize the spatial clustering patterns for all reported dengue
      cases (laboratory-positive and indeterminate) and laboratory-positive cases
      alone, while the Barton and David and Knox tests were used to characterize spatio
      temporal attributes of dengue cases reported during the 1991-1992 outbreak. For
      both sets of data significant case clustering was identified within individual
      households over short periods of time (three days or less), but in general, the
      cases had spatial pattern characteristics much like the population pattern as a
      whole. The rapid temporal and spatial progress of the disease within the
      community suggests that control measures should be applied to the entire
      municipality, rather than to the areas immediately surrounding houses of reported
      cases. The potential for incorporating Geographic Information System technologies
      into a dengue surveillance system and the limitations of using surveillance data
      for spatial studies are discussed.

PMID- 9546406
TI  - Diarrheal disease incidence and morbidity among United States military personnel
      during short-term missions overseas.
AB  - Outpatient medical surveillance of U.S. troops was conducted during 11 different
      overseas missions between 1981 and 1990. In addition, at the end of each of 18
      overseas missions during the same period, a sample of troops was queried
      regarding illnesses and exposures experienced in the preceding time overseas.
      Diarrhea was among the leading causes of morbidity during all of these short-term
      missions. Diarrhea incidence rates were found to be highest during summer months,
      and were higher during missions to Thailand (median = 25%, range = 20-29%), Latin
      America (median = 26%, range = 1-43%), and northeastern Africa and southwest Asia
      (median = 19%, range = < 1-52%). Rates were lowest in troops deployed to the
      Republic of South Korea (median = 16%, range = 8-27%). During April and May 1990,
      a focused surveillance and questionnaire study was conducted during a five-week,
      joint U.S.-Thai military training exercise in central Thailand. Among 2,600 U.S.
      personnel, diarrheal illness was found to be the most common medical problem for
      troops (estimated cumulative incidence = 29%). Travel outside of the base of
      operations and consumption of ice were found to be important risk factors. The 10
      year database analyzed for this report is the largest, published summary showing
      the significant impact of diarrheal diseases on U.S. military forces during short
      term deployments to less developed areas.

PMID- 9546408
TI  - Risk factors for primary pulmonary coccidioidomycosis hospitalizations among
      United States Navy and Marine Corps personnel, 1981-1994.
AB  - Recent coccidioidomycosis outbreaks among military personnel have alarmed public
      health officials. We used computerized hospitalization records to identify risk
      factors for coccidioidomycosis hospitalizations among active-duty United States
      Navy and Marine Corps personnel for the years 1981 to 1994. Primary pulmonary
      disease was the most common form of disease, accounting for 82 (73%) of the 113
      first admissions. Crude annual rates of primary pulmonary disease increased
      markedly in 1992 and 1993 in concert with an epidemic in the United States.
      Demographic data from the pulmonary admissions were combined with that of a 2%
      random sample of the entire Navy and Marine Corps population for multivariate
      risk factor modeling. Persons from junior paygrades, older age groups, and those
      reporting a race/ethnicity other than Caucasian or Hispanic were most likely to
      be hospitalized with this disease. These risk factor data should be considered in
      designing coccidioidomycosis surveillance and prevention programs.

PMID- 9546407
TI  - Helicobacter pylori serostatus in backpackers following travel to tropical
      countries.
AB  - The mode of transmission of Helicobacter pylori is unknown. The seroprevalence of
      H. pylori and the rate of transmission of feco-oral pathogens in developing
      countries are both high. Long-term travelers to these regions, who come from
      developed countries are thus potentially at increased risk of an infection with
      this bacterium. We studied the H. pylori serology status before and after travel
      of 104 backpackers who traveled to tropical countries; 76 medical students who
      did not leave Israel served as controls. Southeast Asia (70%) and South America
      (24%) were the major destinations, but the area of travel had no effect on the
      seroconversion rate. The total time spent abroad was 53 person-years. Thirty six
      of the travelers and 30 controls were positive at the outset. Seropositivity at
      entry was significantly associated with being a Sepharadic Jew or having a parent
      with a peptic ulcer disease. The majority of travelers (86.5%) and controls
      (92.1%) did not change their serostatus. Four travelers seroconverted, but 10
      seroreverted, while three controls seroconverted, and three others seroreverted.
      No significant association with gastroenteritis was found. Serostatus may have
      been affected by mefloquine use because none of the four seroconverters, but
      eight of 10 seroreverters used it as malaria prophylaxis. In vitro studies
      demonstrated that mefloquine has anti-H. pylori activity. Feco-oral transmission
      is apparently not an important route of transmission of this organism among
      travelers.

PMID- 9546409
TI  - Application of the enzyme-linked immunoelectrotransfer blot to filter paper blood
      spots to estimate seroprevalence of cysticercosis in Bolivia.
AB  - An enzyme-linked immunoelectrotransfer blot (EITB) assay was used to study the
      prevalence of cysticercosis in rural Bolivia. Dried blood spots on filter paper
      from fingersticks were used as assay samples. Before the serosurvey, experiments
      were performed to show that samples eluted from dried whole blood on filter paper
      exhibited no decrease in sensitivity when compared with the more traditional
      serum samples used in the EITB. Fingerstick blood dried on filter paper is a
      convenient, economical way of transporting and storing field samples for
      epidemiologic surveys of cysticercosis in developing countries. This report shows
      the utility of this sample collection method in underdeveloped countries where
      refrigeration is not possible and where venipuncture is a problem. Blood was
      obtained from randomly selected residents in three rural regions of Bolivia:
      Chuquisaca (n = 1,859), Cochabamba (n = 1,516), and Tarija (n = 1,010). The
      estimated seroprevalence on 10% of the sample collected for the three regions
      were 9%, 4.5%, and 2%, respectively.

PMID- 9546410
TI  - Short report: gnathostomiasis in Mexico.
AB  - Gnathostomiasis is an important food-borne parasitic zoonosis that is endemic
      mainly in Asian countries where some people prefer to eat raw freshwater fish. In
      North America, the first recorded case of gnathostomiasis was in Mexico in 1970,
      and the numbers of gnathostomiasis patients in Mexico seems to be increasing
      dramatically with time. However, the epidemiology of this disease in Mexico has
      never been described in detail. Here we review the current status of
      gnathostomiasis in Mexico.

PMID- 9546411
TI  - Postpartum cardiac failure in Sudanese-Sahelian Africa: clinical prevalence in
      western Niger.
AB  - Postpartum cardiac failure (PPCF) is the most frequent clinical form of heart
      failure in hospitalized women in Sudanese-Sahelian Africa. We have previously
      studied this disease in a hospital setting. Although the incidence is relatively
      high in rural areas, no systematic field study has been carried out. In this
      report, we describe a retrospective study conducted in the western part of Niger
      in July-August 1991. Sixty-two villages were visited and a thorough search for
      patients was initiated (from a population of 79,941 inhabitants, 19,941 females
      14-40 years of age, corrected census of 1988). Twenty-eight patients from 27
      villages were included. The subject patients were those presenting with
      predefined symptoms (dyspnea and cough) and physical signs (edema of the legs) of
      congestive heart failure during the six-month period following delivery. Apart
      from arterial hypertension and previous PPCF, diagnosis of another cardiac
      disease was an exclusion criterion. The prevalence of PPCF was 1.40 per 1,000
      females of child-bearing age. The clinical profiles of these cases were in
      accordance with those of a previous study in 1989 carried out at Niamey Hospital.
      These results were a mean +/- SD age of 28 +/- 7 years, multiparity (mean = 4
      children), poor socioeconomic status, postpartum ablutions with hot water, and a
      high sodium intake. This is the first study on the clinical prevalence of PPCF in
      a Sudanese/Sahelian population living in a rural area.

PMID- 9546413
TI  - Role of hepatitis E virus in sporadic cases of acute and fulminant hepatitis in
      an endemic area (Chad).
AB  - Forty-one patients with acute or fulminant hepatitis and 86 control patients were
      entered into a study of sporadic, acute, and fulminant hepatitis in the N'Djamena
      area of Chad in 1993. Acute hepatitis B was diagnosed in nine (22%) patients and
      acute hepatitis E in 27 (66%) patients. No acute hepatitis A was observed and 10%
      of the patients had serologic markers of hepatitis C virus (HCV) infection. Dual
      acute hepatitis B and E were observed in four patients (10%) and acute HEV
      infection was associated with chronic hepatitis B surface antigen carriage in 16
      (39%). Epidemiologic findings concerning HBV from Chad suggest that these
      patients had undiagnosed chronic liver disease due to HBV, with acute
      deterioration caused by superimposed HEV replication. Moreover, it is obvious
      that in developing countries only the most severe cases of hepatitis are seen in
      hospital settings and a large proportion of them are related to superinfection
      with HBV and HEV. Antibody to HEV was observed in 22% of the control patients.
      This observation and the fact that epidemic and sporadic cases of HEV are
      observed in Chad indicates that HEV is highly endemic in this country.

PMID- 9546412
TI  - Japanese encephalitis among hospitalized pediatric and adult patients with acute
      encephalitis syndrome in Hanoi, Vietnam 1995.
AB  - The etiologic spectrum of acute encephalitis syndrome (AES) has not been well
      defined in Vietnam. Cohort and case-control studies were performed on all adult
      and pediatric AES patients admitted to the Neurology Service of Bach Mai Hospital
      between June 5 and August 3, 1995. Among pediatric AES patients, 31 (67%) of 46
      had acute Japanese encephalitis (JE), compared with only two (6%) of 33 adult AES
      patients (P < 0.0001). For confirmed JE cases, serum specimens obtained 15-21
      days after symptom onset had the highest mean anti-JE IgM signal-to-noise (P/N)
      ratios (8.08 + 1.09 SE). A serosurvey of adult household members did not reveal
      any cases of recent subclinical JE infection, although 26% had evidence of past
      JE infection. The use of bed netting was nearly universal but did not appear to
      reduce the risk of AES or JE. Given the high incidence of JE, particularly among
      children, Vietnam seems well suited for the development of a targeted JE
      vaccination strategy.

PMID- 9546414
TI  - A case study of cytokine profiles in acute human babesiosis.
AB  - The immune response in a patient with acute babesiosis was determined by
      measurements of lymphocyte subpopulations, serum levels of cytokines, and
      adhesion molecules. The ratio of CD4+:CD8+ lymphocytes was reduced early in the
      infection, but returned to a normal value after treatment with azithromycin and
      quinine. Natural killer (NK) cells markedly increased in the acute phase but
      progressively decreased and to the normal range in the convalescent phase. Serum
      levels of tumor necrosis factor-alpha, interferon-gamma, interleukin-2 (IL-2), IL
      6, E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion
      molecule-1 were highly elevated in the acute phase while normal levels of these
      mediators were observed one month after treatment. These results suggest that
      CD8+ T cells and NK cells may be involved in the host defense mechanisms against
      acute babesiosis.

PMID- 9546415
TI  - Increase in asialoganglioside- and monosialoganglioside-reactive antibodies in
      chronic Chagas' disease patients.
AB  - Antibodies reactive with the core glycan of asialoganglioside (GA1),
      monosialoganglioside (GM1), and disialoganglioside (GD1a) were studied in human
      sera. In healthy individuals, GA1-, GM1-, and GD1a-reactive antibodies were
      mainly of the IgM class, but also of the IgA and IgG classes, and were present at
      low titers in the serum of 68%, 79%, and 91% of the individuals studied,
      respectively. Levels of anti-GA1 and anti-GM1 antibodies, mainly of the IgA and
      IgG classes, were significantly elevated (P < 0.001) in 62% and 72% of subjects,
      respectively, chronically infected with Trypanosoma cruzi, with no association
      found with the degree of myocardial damage. No significant increase in anti-GA1
      and anti-GM1 antibodies was found in dilated cardiomyopathy patients. The level
      of anti-GD1a antibody was not significantly different between healthy controls
      and chronic chagasic or dilatatory cardiomyopathy patients. Since the peripheral
      nervous system is very rich in gangliosides, it is possible that the increases in
      GA1- and GM1-specific antibodies that develop during chronic T. cruzi infection
      are involved in the pathology of peripheral neuropathy in Chagas' disease.

PMID- 9546416
TI  - Effect of pentoxifylline on cytokine patterns in the therapy of complicated
      Plasmodium falciparum malaria.
AB  - The effect of pentoxifylline (PTX) was tested for its capacity to modulate
      cytokine responses during therapy of severe Plasmodium falciparum malaria in a
      placebo-controlled, randomized study in 45 adult patients in Bangkok, Thailand.
      The patients received standard antimalarial treatment with artesunate (120 mg
      intravenously given immediately, then 60 mg every 12 hr for a total dose of 600
      mg). The patients received either low-dose PTX (20 mg/kg/day, n = 15), high-dose
      PTX (40 mg/kg/day, n = 15), or placebo (n = 15) as continuous infusion for the
      first three days of antimalarial treatment. Tumor necrosis factor (TNF) and
      interleukin-6 (IL-6) plasma levels were markedly elevated in all patients prior
      to treatment. After 6 hr of high-dose PTX treatment, TNF and IL-6 levels
      significantly decreased while an increase in TNF and IL-6 levels was seen after 6
      hr of low-dose PTX or placebo treatment (P < 0.01). After 12 and 24 hr of high
      dose PTX infusion, TNF-receptor plasma concentrations were lower than in low-dose
      PTX- or placebo-treated patients (P < 0.01), whereas no differences between the
      groups with regard to IL-6 receptor levels were observed. We conclude that 40
      mg/kg/day of PTX reduces plasma levels of TNF, IL-6, and TNF-receptor in patients
      with severe malaria. Whether this reduction improves clinical outcome remains to
      be determined.

PMID- 9546417
TI  - Pentoxifylline as an ancillary treatment for severe falciparum malaria in
      Thailand.
AB  - Pentoxifylline, an inhibitor of tumor necrosis factor, has been evaluated as an
      antimalarial agent in combination with artesunate in 45 patients with severe
      falciparum malaria. Patients were admitted to the intensive care unit at the
      Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to
      treatment for 72 hr with a combination of intravenously administered artesunate
      and 1) placebo, 2) low-dose pentoxifylline (0.83 mg/kg/hr), or 3) high-dose
      pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of
      severe malaria such as cerebral malaria (n = 18), renal failure requiring
      hemodialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n
      = 30). The overall severity was comparable in the three groups. Clinical outcome
      was assessed with respect to the parasite clearance time and the fever clearance
      time in all patients. In addition, a number of subsidiary outcome variables were
      examined in specific subgroups, including the recovery time from coma for
      patients with cerebral malaria, the duration of intubation in patients with
      respiratory distress, the number of hemodialysis treatments needed for patients
      with acute renal failure, and the number of units of blood administered to
      patients requiring transfusion. Concentrations of tumor necrosis factor were
      reduced in all three groups at 48 hr after treatment. No significant differences
      among the three treatment groups were found for any of the outcome variables
      examined. We conclude that the addition of pentoxifylline to artesunate therapy
      for severe malaria produced no evident clinical benefit.

PMID- 9546418
TI  - In vitro activity of artemether against African isolates (Senegal) of Plasmodium
      falciparum in comparison with standard antimalarial drugs.
AB  - The in vitro activity of artemether against 56 African isolates of Plasmodium
      falciparum from Senegal was evaluated using an isotope-based drug susceptibility
      semi-microtest. The 50% inhibitory concentration (IC50) values for artemether
      were in a narrow range from 0.8 to 15.2 nM (mean IC50 = 3.43 nM) and the 95%
      confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on
      chloroquine-sensitive and chloroquine-resistant isolates (mean IC50 = 346 nM, 95%
      CI = 2.08-4.84 nM versus mean IC50 = 2.80 nM, 95% CI = 2.00-3.60 nM). There was a
      significant positive correlation between responses to artemether and mefloquine
      (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.085, P < 0.05), artemether
      and halofantrine (r2 = 0.075, P < 0.05), quinine and mefloquine (r2 = 0.205, P <
      0.01), quinine and halofantrine (r2 = 0.124, P < 0.05), and mefloquine and
      halofantrine (r2 = 0.801, P < 0.001). A positive correlation between these drugs
      suggests in vitro cross-resistance or at least in vitro cross-susceptibility.

PMID- 9546419
TI  - Assessment of the effect of the oral iron chelator deferiprone on asymptomatic
      Plasmodium falciparum parasitemia in humans.
AB  - While the parenteral iron-chelating agent desferrioxamine B has anti-malarial
      activity in humans, the usefulness of an orally active chelator for this
      indication has not been investigated previously in vivo. We conducted a
      prospective, double-blind, placebo-controlled, cross-over trial of deferiprone
      (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with
      asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered
      daily for three or four days in divided doses of 75 or 100 mg/kg of body weight,
      dosages that are effective for treating iron overload. No reduction in asexual
      intra-erythrocytic parasites was observed during or after deferiprone treatment.
      The mean peak plasma concentration of deferiprone (108.9 +/- 24.9 micromol/L)
      achieved was within the range demonstrated to inhibit the growth of P. falciparum
      in vitro, but the systemic exposure as determined by the 24-hr plasma
      concentration-time curve would not be predicted inhibit growth in vivo. No
      evidence of deferiprone-associated hematological toxicity was noted in this short
      term study of these subjects, all of whom had clinical evidence of normal body
      iron stores. Because of the risk of neutropenia and other adverse effects with
      higher doses or prolonged use of the chelator, additional trials of deferiprone
      as a sole anti-malarial agent would not seem to be justified. In contrast,
      further efforts are needed to develop other orally active iron-chelating agents
      specifically for their anti-malarial action.

PMID- 9546420
TI  - Plasma levels of artesunate and dihydroartemisinin in children with Plasmodium
      falciparum malaria in Gabon after administration of 50-milligram artesunate
      suppositories.
AB  - A thermostable suppository of artesunate (artesunic acid) has been developed. In
      Gabon, 12 children with Plasmodium falciparum malaria received two
      administrations of this suppository in a 4-hr interval. Parasitemia and fever
      were then measured and the plasma levels of artesunate and its active metabolite,
      dihydroartemisinin, were determined by means of a reversed phase high-pressure
      liquid chromatography method using reductive electrochemical detection.
      Substantial parasite clearance (97-100%) was noted 24 hr after the beginning of
      the treatment and body temperature had returned to normal. Absorption,
      metabolism, and elimination of artesunate were rapid. Mean values of maximum
      plasma levels (Cmax) and maximum concentration peak times (tmax) were evaluated.
      The Cmax of dihydroartemisinin (0.18 +/- 0.10 microg/ml [mean +/- SE]) was higher
      than the Cmax of artesunate (0.09 +/- 0.04 microg/ml) and the tmax of
      dihydroartemisinin (1.13 +/- 0.58 hr) was higher than the tmax of artesunate
      (0.58 +/- 0.19 hr). Plasma levels 30 min after the second suppository
      administration were not consistently higher than those found 30 min after the
      first administration.

PMID- 9546421
TI  - Molecular epidemiology of malaria in Yaounde, Cameroon I. Analysis of point
      mutations in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium
      falciparum.
AB  - Resistance to antifolate antimalarial drugs (cycloguanil, a biologically active
      metabolite of proguanil, and pyrimethamine) is associated with a Ser- to Asn-108
      point mutation in the dihydrofolate reductase-thymidylate synthase gene of
      Plasmodium falciparum. The frequency of this mutation was studied in 127 clinical
      isolates obtained in Yaounde, Cameroon using a simple and rapid molecular
      technique based on the polymerase chain reaction and restriction fragment length
      polymorphism. Of the 127 isolates, pure wild-type Ser-108 codon, pure mutant-type
      Asn-108 codon, and mixed codons were observed in 66, 55, and six parasites,
      respectively. The proportion of antifolate-resistant, pure mutant-type codon,
      with respect to pure wild-type or mixed alleles, was 43% (55 of 127). The results
      of the molecular assay were compared with those of semimicro isotopic in vitro
      assay in 34 isolates. All 17 pure Ser-108 isolates and two isolates with mixed
      alleles were sensitive to both pyrimethamine (50% inhibitory concentration [IC50]
      < 100 nM) and cycloguanil (IC50 < 50 nM). Fourteen of 15 isolates with the mutant
      type Asn-108 codon were resistant to pyrimethamine and cycloguanil. One isolate
      with Asn-108 showed a slightly elevated pyrimethamine IC50 (78 nM), which was
      within the sensitive range. This study provides further evidence that antifolate
      resistant P. falciparum isolates are already present in Yaounde, Cameroon.

PMID- 9546422
TI  - Molecular epidemiology of malaria in Yaounde, Cameroon II. Baseline frequency of
      point mutations in the dihydropteroate synthase gene of Plasmodium falciparum.
AB  - Sulfadoxine-pyrimethamine is one of the alternative antimalarial drugs used to
      treat chloroquine-resistant Plasmodium falciparum malaria. The molecular target
      of sulfadoxine, an analog of p-aminobenzoic acid that inhibits the folate
      biosynthetic pathway, is dihydropteroate synthase (DHPS). The nucleotide sequence
      of the DHPS gene was determined in 32 clinical isolates obtained in Yaounde,
      Cameroon, and compared with the sequence of reference clones and Cambodian
      strains of P. falciparum. Of the 32 Cameroonian isolates, 31 displayed one of the
      sulfadoxine-sensitive mutation patterns: Ala-436/Ala-437/Ala-581/Ala-613 (n =
      20), Ser-436/Gly-437/Ala-581/Ala-613 (n = 6), Ser-436/Ala-437/Ala-581/Ala-613 (n
      = 4), and Ala-436/Gly-437/Ala-581/Ala-613 (n = 1). One isolate had a sulfadoxine
      resistant profile characterized by a double mutation: Phe-436/Ala-437/Ala-581/Ser
      613. Although the majority of the isolates had a sulfadoxine-sensitive genetic
      profile, further studies are needed to correlate the mutation patterns and in
      vitro and in vivo sulfadoxine sensitivity.

PMID- 9546423
TI  - Evaluation of SPf66 malaria vaccine efficacy in Brazil.
AB  - This paper reports the efficacy results of the randomized, placebo-controlled,
      field trial of SPf66 malaria vaccine in Costa Marques, Rondonia, Brazil. This
      region is characterized by the seasonal distribution of Plasmodium falciparum and
      P. vivax infections, and the recent occupation by migrants from nonendemic areas.
      A total of 800 individuals of both sexes, ranging in age from seven to 60 years,
      were included in the study. Of the initial cohort, 572 participants completed the
      vaccination schedule. Clinical and parasitologic evaluations were obtained by
      active and passive searches on a periodic basis. The overall protective efficacy
      against P. falciparum infections was -1.6% (-32.9% to 22.4%), and 14.1% (-17.0%
      to 36.9%) for the first episode. The overall protective efficacy for P. vivax
      infections was -19.7% (-44.8% to 1.03%), and -10.8% (-41.1% to 12.8%) for the
      first episode. No statistical evidence of an overall significant protective
      effect of SPf66 malaria vaccine against P. falciparum and P. vivax malaria was
      obtained in this trial.

PMID- 9546424
TI  - Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as
      the binding site for Crk proteins.
AB  - Tyr-762 is an autophosphorylation site in the human platelet-derived growth
      factor (PDGF) alpha-receptor. In order to investigate whether phosphorylated Tyr
      762 serves as a docking site for downstream signal transduction molecules,
      affinity purification using an immobilized synthetic peptide containing
      phosphorylated Tyr-762 and its surrounding amino acid residues was performed.
      Proteins in HeLa cell lysate of molecular sizes 27, 38 and 40 kDa bound to the
      phosphorylated, but not to the unphosphorylated peptide. Analyses of partial
      amino acid sequences of the purified proteins indicated that they were identical
      to CrkI, CrkII and CrkL respectively. The wild-type PDGF alpha-receptor, when
      expressed in porcine aortic endothelial cells, formed complexes with CrkII and
      CrkL upon ligand stimulation, which was specifically inhibited by a synthetic
      peptide containing phosphorylated Tyr-762. Replacement of Tyr-762 with a
      phenylalanine residue in the PDGF alpha-receptor abrogated ligand-induced binding
      of Crk proteins. Tyrosine phosphorylation of CrkII and CrkL increased by 1.8- and
      1.3-fold, respectively, upon ligand stimulation of the wild-type alpha-receptor.
      In contrast, the Y762F mutant PDGF alpha-receptor failed to induce tyrosine
      phosphorylation of Crk proteins. CrkII and CrkL constitutively formed complex
      with the guanine nucleotide exchange factor C3G, in unstimulated as well as PDGF
      stimulated cells. Moreover, the activated wild-type PDGF alpha-receptor but not
      the Y762F mutant receptor was found in a C3G immunoprecipitate, suggesting that a
      ternary complex between the activated PDGF alpha-receptor, Crk and C3G was
      formed. DNA synthesis stimulated by PDGF-BB as well as PDGF-induced MAP kinase
      activation was similar in cells expressing wild-type and mutant receptors.
      Interestingly, the activated PDGF beta-receptor was found not to bind Crk
      proteins. Instead, Tyr-771 of the beta-receptor, which is localized at an
      analogous position to Tyr-762 in the alpha-receptor, binds RasGAP. RasGAP is not
      bound to the alpha-receptor. Thus, this region in the kinase inserts of the two
      receptors may be important for the divergency in signaling from the two PDGF
      receptors.

PMID- 9546425
TI  - Slow repair of bulky DNA adducts along the nontranscribed strand of the human p53
      gene may explain the strand bias of transversion mutations in cancers.
AB  - Using UvrABC incision in combination with ligation-mediated PCR (LMPCR) we have
      previously shown that benzo(a)pyrene diol epoxide (BPDE) adduct formation along
      the nontranscribed strand of the human p53 gene is highly selective; the
      preferential binding sites coincide with the major mutation hotspots found in
      human lung cancers. Both sequence-dependent adduct formation and repair may
      contribute to these mutation hotspots in tumor tissues. To test this possibility,
      we have extended our previous studies by mapping the BPDE adduct distribution in
      the transcribed strand of the p53 gene and quantifying the rates of repair for
      individual damaged bases in exons 5, 7, and 8 for both DNA strands of this gene
      in normal human fibroblasts. We found that: (i) on both strands, BPDE adducts
      preferentially form at CpG sequences, and (ii) repair of BPDE adducts in the
      transcribed DNA strand is consistently faster than repair of adducts in the
      nontranscribed strand, while repair at the major damage hotspots (guanines at
      codons 157, 248 and 273) in the nontranscribed strand is two to four times slower
      than repair at other damage sites. These results strongly suggest that both
      preferential adduct formation and slow repair lead to hotspots for mutations at
      codons 157, 248 and 273, and that the strand bias of bulky adduct repair is
      primarily responsible for the strand bias of G to T transversion mutations
      observed in the p53 gene in human cancers.

PMID- 9546427
TI  - Mismatch repair deficiency leads to a unique mode of colorectal tumorigenesis
      characterized by intratumoral heterogeneity.
AB  - In order to determine the effects of mismatch repair (MMR) deficiencies in
      sporadic colorectal carcinomas, 45 such cancers were examined using a sensitive
      method called crypt isolation technique. Loss of heterozygosity (LOH) in the MSH2
      or MLH1 gene was more frequently observed in replication error (RER) (+)
      carcinomas than in RER (-) carcinomas, which implied that loss of one normal
      allele could partly affect repair capacity. MSH2 gene defects at both alleles
      were observed in two carcinomas, which showed severe repair deficiencies.
      Interestingly, unlike the situation observed in the p53 gene, the MSH2 and MLH1
      genes did not show complete LOH. Novel crypt isolation-based subpopulation (CISP)
      analysis demonstrated that at least two distinct carcinoma subpopulations existed
      in most carcinomas that showed incomplete LOH; one with and one without LOH. In
      one carcinoma that had germline mutation and somatic incomplete LOH of the MSH2
      gene, the mutator phenotype was only observed in populations affected in both
      alleles. Thus, the MSH2 gene appears to possess the two hits mechanism of tumor
      suppressor genes. However, unlike the tumor suppressor genes, MMR gene defects
      lead to a unique mode of colorectal tumorigenesis characterized by intratumoral
      heterogeneity.

PMID- 9546426
TI  - The oncogenic ErbB-2/ErbB-3 heterodimer is a surrogate receptor of the epidermal
      growth factor and betacellulin.
AB  - The ErbB-1 receptor tyrosine kinase binds to six different growth factors, whose
      prototype is the epidermal growth factor (EGF). Two homologous epithelial
      receptors, ErbB-3 and ErbB-4, bind all isoforms of another family of growth
      factors, the Neu differentiation factors (NDFs/neuregulins). The fourth member of
      the ErbB family, ErbB-2, acts as the preferred heterodimeric partner of ligand
      occupied complexes of the three other ErbB proteins. Here we report that at high
      concentrations, EGF can induce cell growth and differentiation in the absence of
      ErbB-1. This function is shared by betacellulin, but not by three other ligands,
      including the transforming growth factor alpha (TGFalpha). The functional
      receptor was identified as a heterodimer between ErbB-3 and ErbB-2, a previously
      identified oncogenic complex. When singly expressed, neither ErbB-3 nor ErbB-2
      can mediate signaling by EGF. In addition, when co-expressed, blocking either
      receptor by using site-specific antibodies inhibited EGF and betacellulin
      activities, indicating strict cooperativity between ErbB-3 and ErbB-2. Through
      analysis of chimeras between EGF and TGFalpha, we identified the middle portion
      of EGF (loop B) as the site that enables activation of ErbB-2/ErbB-3. In
      conclusion, cooperative and promiscuous binding of stroma-derived growth factors
      by the epithelium-expressed ErbB-2/ErbB-3 heterodimer may be significant to
      cancer development. The mechanistic implications of our results for a model that
      attributes receptor dimerization to ligand bivalency, as well as to a recently
      proposed mechanism of secondary dimerization, are discussed.

PMID- 9546428
TI  - Deregulated expression of E2F1 induces hyperplasia and cooperates with ras in
      skin tumor development.
AB  - In cell culture studies, overexpression of the E2F1 transcription factor has been
      shown to stimulate proliferation, induce apoptosis, and cooperate with an
      activated ras gene to oncogenically transform primary rodent cells. To study the
      effect of increased E2F1 activity on epithelial growth and tumorigenesis in vivo,
      transgenic mice expressing E2F1 under the control of a keratin 5 (K5) promoter
      were generated. Expression of E2F1 in the epidermis results in hyperplasia but
      does not inhibit terminal differentiation. In a transgenic line expressing high
      levels of E2F1, mice have decreased hair growth likely as a result of aberrant
      apoptosis in developing hair follicles. Coexpression of a cyclin D1 transgene
      with E2F1 augments epidermal hyperplasia and further disrupts hair follicle
      development suggesting that hypophosphorylated Rb antagonizes the proliferative
      and apoptotic-promoting activities of E2F1. Finally, the E2F1 transgene is found
      to cooperate with a v-Ha-ras transgene to induce skin tumors in double transgenic
      animals. These findings confirm that many of the activities ascribed to E2F1
      through in vitro studies can be reproduced in vivo and demonstrate for the first
      time that deregulated E2F activity can contribute to tumor development.

PMID- 9546429
TI  - Oncogenic activation of a human cyclin A2 targeted to the endoplasmic reticulum
      upon hepatitis B virus genome insertion.
AB  - Cyclins are major cell cycle regulators which role in malignant transformation
      remains controversial. In this report we describe a new mechanism of cyclin
      oncogenic activation. We demonstrate that an altered form of cyclin A2 (S2A)
      which N-terminal part is replaced by the hepatitis B virus envelope protein
      transforms normal rat kidney cells and cooperates with ras to transform rat
      embryo fibroblasts. In contrast, neither the viral moiety, nor a full length or N
      terminally deleted cyclin A2 show these oncogenic properties. S2A oncogenicity
      arises from its binding to cyclin dependent kinases, since mutation in the MRAIL
      sequence abolishes transformation and correlates with an abnormal cellular
      localization in the endoplasmic reticulum membrane. Together, these results
      implicate modification in the cellular distribution of a cell cycle regulator as
      a mechanism of virally-induced transformation.

PMID- 9546430
TI  - E2F-3 accumulation is regulated by polypeptide stability.
AB  - E2F is a complex family of transcription factors which appears to regulate the
      transcription of genes required for the S phase of the mammalian cell cycle. In
      the present work, we have examined the mechanisms regulating E2F-3 accumulation
      in mouse fibroblasts. We have determined that E2F-3 DNA binding activity is
      restricted to the G1/S transition and S phase in both normal BALB/c-3T3
      fibroblasts and in an SV40 virus-transformed BALB/c-3T3 derivative. Immunoblot
      analysis indicates that G0 and G1 cells have little or no E2F-3 polypeptide and
      that the increase in the DNA binding activity of E2F-3 at the G1/S boundary is
      reflected by an increase in total E2F-3 protein. In contrast to the E2F-3
      polypeptide, RNAse protection assays demonstrate that the E2F-3 mRNA is clearly
      present in G0 and G1 cells. Finally, pulse/chase experiments indicate that the
      half-life of E2F-3 is approximately 40-fold greater in cells blocked in S phase
      relative to asynchronously growing cells. Together, these results indicate that
      the accumulation E2F-3 at S phase may be regulated, at least in part, at the
      level of protein stability.

PMID- 9546431
TI  - Human smooth muscle alpha-actin gene is a transcriptional target of the p53 tumor
      suppressor protein.
AB  - Smooth muscle (sm) alpha-actin is expressed in vascular smooth muscle cells and
      fibroblast cells. Its expression is regulated by cell proliferation and repressed
      during oncogenic transformation. In this study, we demonstrate that p53
      activation is associated with a dramatic increase in organized microfilament
      bundles and an increase in sm alpha-actin mRNA level. Wild-type p53, but not
      mutant p53, strongly stimulated human sm alpha-actin promoter activity in p53
      null cell lines. The sequences homologous to the p53 consensus sequence and to
      the p53 binding sequence from the muscle creatine kinase, were found within a
      specific region of the sm alpha-actin promoter. This sequence was sufficient to
      confer p53-dependent activation to a heterologous promoter and p53 was capable of
      binding to this sequence as assessed by gel shift analysis. Ionizing irradiation
      of colorectal tumor cells caused an increase in alpha-actin mRNA level in a p53
      dependent manner. Taken together, these results demonstrate that human sm alpha
      actin gene is a transcriptional target for p53 tumor suppressor protein and
      represents the first example of a cytoskeletal gene with a functionally defined
      p53 response element.

PMID- 9546432
TI  - Molecular analysis of the IL-2 receptor beta chain gene expressed in human tumor
      cells.
AB  - Interleukin-2 (IL-2) is recognized as a T cell growth factor. We have previously
      reported that human carcinoma cell lines are inhibited in growth by exogenous IL
      2, which binds to the IL-2 receptor beta (IL-2Rbeta) chain ubiquitously expressed
      on the surface of tumor cells. A possibility was considered that IL-2Rbeta on
      carcinomas responsible for negative signaling was different from that expressed
      on hematopoietic cells. To investigate this possibility, mRNA for the IL-2Rbeta
      chain was amplified and compared in carcinoma and lymphoid cells. Using RT-PCR
      with pairs of sense-antisense oligonucleotide primers specific for the various
      regions of extracellular, transmembrane and intracellular domains of the IL
      2Rbeta chain, we amplified mRNA obtained from three human carcinoma cell lines
      and human lymphoid cells as controls. The identity of the amplicons was confirmed
      by Southern analysis with the 32P-labeled cDNA probe coding for the entire span
      of the IL-2Rbeta chain. In addition, genomic DNA obtained from the tumor cell
      lines was sequenced to examine the possibility that a mutation is present in the
      gene coding for the intracellular IL-2Rbeta chain domain. No mutations or
      deletions were detected. The message for all three domains of the beta chain was
      identical in tumor cells and in normal lymphoid cells used as controls. Also, by
      Western blot and northern analyses no differences between IL-2Rbeta chain in
      tumors vs that expressed in lymphoid cells were demonstrable. The IL-2Rgamma
      chain, which participates in IL-2/IL-2R signaling pathway, was expressed in tumor
      cells. Expression of JAK1 transcripts in these cells was comparable to that in
      lymphocytes. However, RT-PCR analysis identified differences in expression of
      JAK3 splice variants (B and M) in tumor cells. These differences may be
      responsible for altered downstream signaling by IL-2. Overall, our data indicate
      that the same IL-2/IL-2R pathway is operative in human carcinomas and in normal
      epithelial or lymphoid cells.

PMID- 9546433
TI  - Abl protein kinase abrogates the response of multipotent haemopoietic cells to
      the growth inhibitor macrophage inflammatory protein-1 alpha.
AB  - The clonogenic cells of chronic myeloid leukaemia (CML), unlike normal
      haemopoietic progenitor cells, are resistant to the growth inhibitory effects of
      the chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha). CML is also
      relatively resistant to chemotherapy and the disease is difficult to cure using
      conventional therapeutic routes. CML is associated with increased abl oncogene
      protein tyrosine kinase (PTK) activity. Here, we have tested the hypothesis that
      these aberrant responses to MIP-1alpha and the relative resistance to
      chemotherapy are directly related to this increased abl PTK activity in primitive
      haemopoietic cells. To do this we have expressed a temperature sensitive abl PTK
      in a growth factor dependent, multipotent stem cell line (FDCP-Mix) in which
      growth is normally suppressed by MIP-1alpha. In FDCP-Mix cells expressing the ts
      v-abl PTK and grown at the restrictive temperature for PTK activity the cells
      were relatively sensitive to cytotoxic agents such as cytosine arabinoside and 5
      fluorouracil but MIP-1alpha could induce growth inhibition and confer some degree
      of protection from these agents. At the permissive temperature for abl PTK, the
      cells were relatively resistant to cytotoxic drugs and MIP-1alpha treatment
      neither induced growth inhibition nor protected the cells from cytotoxic drug
      induced cell death. This lack of response to MIP-1alpha was not due to receptor
      down modulation as neither the affinity nor the number of 125I-MIP-1alpha binding
      sites was altered by activating Abl PTK. However, MIP-1alpha mediated increases
      in cytosolic Ca2+ levels were abrogated by switching cells to the permissive
      temperature for Abl PTK activity. These data suggest that the relative resistance
      of CML progenitor cells to therapeutic drugs and the lack of response to MIP
      1alpha occurs as a direct consequence of abl PTK activity and involves
      desensitisation of signal transduction events stimulated by MIP-1alpha receptors.
      Thus one contributory mechanism to transformation of primitive haemopoietic cells
      is abrogation of response to a growth inhibitor.

PMID- 9546434
TI  - MMSP tumor cells expressing the EWS/ATF1 oncogene do not support cAMP-inducible
      transcription.
AB  - Malignant Melanoma of Soft Parts (MMSP) is associated with the EWS/ATF1 fusion
      protein that arises due to chromosomal fusion of the Ewings Sarcoma oncogene
      (EWS) and the cellular transcription factor ATF1. EWS/ATF1 can activate several
      cAMP-inducible promoters, suggesting that cellular transformation in MMSP might
      involve constitutive activation of cAMP-inducible promoters. To assess this
      possibility we have examined the status of the cAMP-signaling pathway in the
      available MMSP-derived cell lines (DTC1 and Su-ccs-1) and find that both cell
      lines share several features. First, in contrast to previous effects observed in
      transient assays, three chromosomal promoters containing ATF binding sites are
      not constitutively activated by endogenous EWS/ATF1 in MMSP cells. Second, all
      the components that are known to be required for cAMP-inducible transcription are
      present. Third, phosphorylation of the cAMP-response-element-binding protein
      (CREB) can be efficiently induced by cAMP. Fourth, cAMP is unable to activate
      transcription, as assessed by a GAL4/ATF1 reporter assay and analysis of the c
      fos and adenovirus early promoters. Thus, cell lines derived from MMSP have a
      block to cAMP-signaling that lies downstream of CREB phosphorylation. In light of
      the cAMP-responsiveness of almost all mammalian cell types, our findings suggest
      that the inability to respond to cAMP might be an important feature of MMSP
      cells.

PMID- 9546435
TI  - Expression of a novel form of p21Cip1/Waf1 in UV-irradiated and transformed
      cells.
AB  - The tumor suppressor p53 and its target the CDK inhibitor p21 (Cip1/Waf1) are key
      components of the cellular response to DNA damage. Insight into how p21 is
      regulated in normal cells, and how it may be deregulated in tumor cells is
      important for the understanding of tumorigenesis. p21 was induced in normal human
      diploid fibroblasts after UV irradiation-induced DNA damage, but, at a high dose
      of UV irradiation, a faster mobility form of p21 on SDS-PAGE (designated
      p21delta) was expressed. Surprisingly, in a variety of growing transformed cell
      lines, the level of p21 was low but p21delta was prominent. We found that
      p21delta appeared to be derived through a loss of around 10 amino acids from the
      C-terminus of p21, which theoretically would remove the PCNA binding domain, a
      second cyclin binding domain and the nuclear localization signal sequence.
      Several characteristics distinguish p21 from p21delta. Both the full length p21
      and p21delta could be stabilized by a proteasome inhibitor, but only the full
      length p21 was associated with Cdk2 and PCNA. Consistent with this, gel
      filtration chromatography revealed that all the full length p21 in the cell was
      complexed to other proteins, whereas a significant portion of p21delta was in
      monomeric form. Moreover, p21 was mainly localized to the nucleus, but p21delta
      was mainly localized to the cytoplasm. We propose that the decrease in p21 and
      increase in p21delta could contribute to the deregulation of the cell cycle, and
      could be a mechanism involved in cellular transformation.

PMID- 9546436
TI  - Cloning and characterization of human and mouse telomerase RNA gene promoter
      sequences.
AB  - Variation in telomerase activity is correlated with cellular senescence and
      tumour progression. However, although the enzymatic activity of telomerase has
      been well studied, very little is known about how expression of telomerase genes
      is regulated in mammalian cells. We have therefore cloned the promoter regions of
      the human (hTR), and mouse, (terc), telomerase RNA genes in order to identify the
      regulatory elements controlling telomerase RNA gene transcription. 1.76 kb
      encompassing the hTR gene promoter region was sequenced, as was 4 kb encompassing
      the terc promoter. No significant sequence similarity could be detected in
      comparisons between human and mouse 5'-regions, flanking the transcribed
      sequences. However, both the human and mouse telomerase RNA genes are within CpG
      islands and may therefore be under the regulation of DNA methylation. Transient
      expression of hTR-reporter gene constructs in HeLa and GM847 cells identified the
      elements responsible for promoter activity are contained in a 231 bp region
      upstream of the transcriptional start site. Transient expression of terc-reporter
      gene constructs in Swiss3T3 and A9 cells identified the elements responsible for
      promoter activity are contained in a 73 bp region upstream of the transcriptional
      start site. These studies have implications for novel transcription targeted
      cancer therapies.

PMID- 9546437
TI  - Potential role for wild-type p53 in leukemias with MLL gene translocations.
AB  - We used single-strand conformation polymorphism (SSCP) analysis of p53 exons 4-8
      to screen for possible mutations in 25 pediatric de novo leukemias with
      translocations of the MLL gene at chromosome band 11q23. Of the 25 patients, 21
      were infants. Fifteen cases were acute myeloid leukemia (AML), eight were acute
      lymphoblastic leukemia (ALL), and two cases were biphenotypic. Nineteen cases
      were studied at diagnosis and six at time of relapse. p53 mutations were absent
      in all 19 cases studied at the time of diagnosis. The only mutation was a TGC-
      >TTC transversion (cys-->phe) at codon 141 in exon 5 in a case of infant ALL at
      relapse that occurred by subclone evolution after MLL gene translocation. We
      previously showed that p53 mutations are also absent in pediatric treatment
      related leukemias with MLL gene translocations. The absence of p53 mutations at
      initial transformation may suggest that the anti-apoptotic effect of mutant p53
      is not important in leukemias with MLL gene translocations. Alternatively,
      exogenous DNA damage may be the common feature in treatment-related and de novo
      cases. Since MLL gene translocations may occur through DNA repair and wild-type
      p53 is central to DNA repair, the absence of p53 mutations raises the possibility
      that wild-type p53, not mutant p53, may be important in the genesis of leukemias
      with these translocations.

PMID- 9546438
TI  - Isolation and characterization of a chicken homologue of the Spi-1/PU.1
      transcription factor.
AB  - Spi-1/PU.1 is a member of the Ets family of transcription factors important in
      regulation of hematopoiesis. We have isolated a chicken cDNA homologuous to the
      mammalian Spi-1/PU.1 gene with an open reading frame of 250 amino acids (aa). The
      chicken Spi-1/PU.1 protein is 14 aa and 16 aa shorter than its human and mouse
      counterparts but is extremely well conserved with 78.8% and 75.2% identity
      respectively. The carboxy terminal DNA binding region, or ETS binding domain, is
      100% identical to that of human and mouse. Some differences with the mammalian
      homologues are seen in the N-terminal part of the protein and in the PEST
      connecting domain. However, the differences are mainly conservative and all the
      features underlying functional aspects seem preserved. The major discrepancy lies
      in a 12 aa deletion in an already poorly conserved part of the PEST sequence. Spi
      1/PU.1 transcripts were detected at high levels in spleen and Fabricius bursa of
      chick embryos by Northern blot and in situ hybridization. Our results show that
      the chicken Spi-1/PU.1 protein behaves like a bonafide Spi-1/PU.1 transcription
      factor in its DNA binding and transactivating properties.

PMID- 9546439
TI  - Identification of human p53 mutations with differential effects on the bax and
      p21 promoters using functional assays in yeast.
AB  - Recent studies have suggested that a rare class of p53 mutants found in tumours
      has a subtle transcriptional defect affecting bax induction but not p21
      induction. We have therefore developed simple functional assays in yeast which
      can be used to identify these mutants. Analysis of 51 different mutations
      observed in human tumours showed that all mutants tested scored as mutant with
      the bax reporter strain but nine scored as wild-type with the p21 reporter
      strain. These results, which can be explained by the lower affinity of the p53
      protein for the bax site, may suggest that p21 is not the key target of p53
      mutations in tumours. Since p21 status has recently been shown to modulate the
      chemotherapeutic and radiotherapeutic sensitivities of cancerous cells, the
      functional assays described here may have important clinical implications.

PMID- 9546440
TI  - Anterior cruciate ligament reconstruction.

PMID- 9546441
TI  - Wear of polyethylene in artificial hip joints: superolateral wear of the
      acetabulum.

PMID- 9546442
TI  - Management of the orthopaedic complications of haemophilia.

PMID- 9546443
TI  - Superolateral wear of the acetabulum.

PMID- 9546444
TI  - Microsurgical excision of lateral lumbar disc herniation through an interlaminar
      approach.
AB  - We made a prospective study of 43 consecutive patients treated for intraforaminal
      (34) or extraforaminal (9) herniations of a lumbar disc by excision through an
      interlaminar approach, using an operating microscope. The intraforaminal
      herniations were contained or extruded in 52% and sequestrated in 47%; for
      extraforaminal herniation the proportions were 66% and 33%, respectively. There
      was additional posterolateral protrusion or spinal stenosis at the level of the
      lateral herniation in seven and four cases, respectively. The patients were
      reviewed at three months and two years after surgery. Radiographs showed three
      grades of facetectomy: grade I, removal of 50% or less, grade II, excision of 51%
      to 75%, and grade III, subtotal or total facetectomy. For intraforaminal
      herniations the results were excellent or good in 88% of patients when reviewed
      at three months and in 91% at two years. For extraforaminal herniations, there
      was an excellent or good outcome in 89% of patients in the short term and in all
      in the long term. The facetectomy had been grade I in 14 and grade II in 25; it
      had been grade III in four, but only one had had total facetectomy. No patient
      had developed vertebral hypermobility as a result of the operation. An
      intralaminar approach using an operating microscope can provide adequate access
      to a lateral protrusion. It has the advantage of allowing the treatment of
      posterolateral protrusion or posterior annular bulge and of spinal stenosis at
      the same level.

PMID- 9546445
TI  - Orientation of lumbar pars defects: implications for radiological detection and
      surgical management.
AB  - Lateral oblique radiographs are considered important for the identification of
      spondylolytic lesions, but these projections will give a clear view only when the
      radiological beam is in the plane of the defect. We studied the variation in
      orientation of spondylolytic lesions on CT scans of 34 patients with 69 defects.
      There was a wide variation of angle: only 32% of defects were orientated within
      15 degrees of the 45 degrees lateral oblique plane. Lateral oblique radiographs
      should not be considered as the definitive investigation for spondylolysis. We
      suggest that CT scans with reverse gantry angle are now more appropriate than
      oblique radiography for the assessment of spondylolysis. Variation in the angle
      of the defect may also need consideration when direct repair is being planned.

PMID- 9546446
TI  - Idiopathic scoliosis in twins studied by DNA fingerprinting: the incidence and
      type of scoliosis.
AB  - We investigated 21 pairs of twins for zygosity and idiopathic scoliosis. DNA
      fingerprinting confirmed that 13 pairs were monozygotic and eight were dizygotic.
      There was concordance for idiopathic scoliosis in 92.3% of monozygotic and 62.5%
      of dizygotic twins. Of the 12 pairs of monozygotic twins concordant for
      idiopathic scoliosis, six showed discordant curve patterns but eight had
      differences in Cobb angle of less than 10 degrees. Seven of the ten pairs of
      monozygotic twins had similar back shapes. Our findings suggest that there is a
      genetic factor in the aetiology of idiopathic scoliosis; they also indicate that
      there is a genetic factor in both the severity of the curve and the general shape
      of the back.

PMID- 9546447
TI  - The anatomy of acute scaphoid fractures: a three-dimensional analysis of
      patterns.
AB  - Various classifications of scaphoid fractures have been based on plain
      radiography, but there are difficulties in defining the actual fracture line
      without an appreciation of the three-dimensional anatomy. Radiological fracture
      lines were therefore mapped on transparent methylmethacrylate models of the bone.
      An analysis of 91 acute fractures showed that 11 were apparently incomplete. The
      other 80 showed three basic anatomical patterns: transverse through the waist,
      oblique in the plane of the dorsal sulcus, or of the proximal pole. There was
      some variation and comminution in these patterns, but no distal fractures of the
      body were seen. The interpretation of different radiological projections is
      discussed. The findings have implications for the management and the assessment
      of outcome.

PMID- 9546448
TI  - Rupture of flexor pollicis longus tendon: a complication of volar plating of the
      distal radius.
AB  - We report three complete ruptures and one partial rupture of the flexor pollicis
      longus tendon in association with the insertion of a volar plate for the
      treatment of fracture of the distal radius. Rupture was associated with the
      chronic use of steroids.

PMID- 9546449
TI  - External fixation for phalangeal and metacarpal fractures.
AB  - From 1987 to 1993 we treated 33 patients with 29 phalangeal and seven metacarpal
      fractures by external fixation using a mini-Hoffmann device. There were 27 open
      and 25 comminuted fractures. In 12 patients one or more tendons was involved. The
      mean follow-up was 4.4 years. Complications occurred in ten fractures; two
      required repositioning of the fixator. All the fractures healed. The functional
      results after metacarpal fractures were better than those after phalangeal
      fractures and fractures of the middle phalanx had better recovery than those of
      the proximal phalanx. Twenty-eight of the 33 patients were satisfied with their
      result. External fixation proved to be a suitable technique for stabilising
      unstable, open fractures with severe soft-tissue injuries.

PMID- 9546450
TI  - Resection of the radial head after Mason type-III fractures of the elbow: follow
      up at 16 to 30 years.
AB  - We reviewed 21 patients with Mason type-III fractures of the radial head treated
      by resection, evaluating the results at 16 to 30 years by a standard
      questionnaire and clinical and radiological examination of the elbow and wrist.
      Seventeen patients had an excellent result, three were good and one fair.
      Resection of the radial head is a satisfactory method of treatment of such
      fractures. Prosthetic replacement seems to be indicated only when there is valgus
      instability of the elbow.

PMID- 9546451
TI  - Non-constrained elbow arthroplasty for mutilans deformity in rheumatoid
      arthritis: a report of six cases.
AB  - Six highly unstable elbows with severe bone loss due to rheumatoid arthritis were
      replaced by a non-constrained, unlinked prosthesis. Bone defects were filled with
      autogenous bone grafts. The mean follow-up was 4.5 years (2 to 8). The clinical
      results were excellent in four elbows and good in two, with good varus-valgus
      stability in all. Radiological follow-up showed no appreciable signs of
      loosening, and the bone grafts had retained most of their original size, with
      minimal resorption. There were no major complications such as dislocation, skin
      necrosis, infection or ulnar neuropathy. The study has shown that the so-called
      mutilans elbow can be successfully replaced using a properly selected type of non
      constrained, unlinked prosthesis with bone grafting of the major defects.

PMID- 9546452
TI  - The posterior interosseous nerve and the posterolateral approach to the proximal
      radius.
AB  - We dissected 21 cadaver elbows to determine the relationship of the posterior
      interosseous nerve to the posterolateral approach to the elbow and head of the
      radius. At the distal end of the exposure the first branches at risk, those to
      extensor carpi ulnaris, were on average 6.0 +/- 1.0 cm (4.0 to 8.4) from the
      articular surface of the radial head. When using the posterolateral approach it
      is important that the interval between extensor carpi ulnaris and anconeus is
      clearly identified with the forearm fully pronated. The supinator should be
      released close to its ulnar border. It is safe to expose the proximal radius as
      far as the distal aspect of the bicipital tuberosity.

PMID- 9546453
TI  - Epidemiology of fractures in 15,000 adults: the influence of age and gender.
AB  - We report a prospective study of the incidence of fractures in the adult
      population of Edinburgh, related to age and gender. Over a two-year period,
      15,293 adults, 7428 males and 7865 females, sustained a fracture, and 5208
      (34.0%) required admission. Between 15 and 49 years of age, males were 2.9 times
      more likely to sustain a fracture than females (95% CI 2.7 to 3.1). Over the age
      of 60 years, females were 2.3 times more likely to sustain a fracture than males
      (95% CI 2.1 to 2.4). There were three main peaks of fracture distribution: the
      first was in young adult males, the second was in elderly patients of both
      genders, mainly in metaphyseal bone such as the proximal femur, although
      diaphyseal fractures also showed an increase in incidence. The third increase in
      the incidence of fractures, especially of the wrist, was seen to start at 40
      years of age in women. Our study has also shown that 'osteoporotic' fractures
      became evident in women earlier than expected, and that they were not entirely a
      postmenopausal phenomenon.

PMID- 9546454
TI  - The epidemiology of humeral shaft fractures.
AB  - We have analysed 249 consecutive fractures of the humeral shaft treated over a
      three-year period. The fractures were defined by their AO morphology, position,
      the age and gender of the patient and the mechanism of injury. Open fractures
      were classified using the Gustilo system and soft-tissue injury, and closed
      fractures using the Tscherne system. The fractures were classified as AO type A
      in 63.3%, type B in 26.2% and type C in 10.4%. Most (60%) occurred in the middle
      third of the diaphysis with 30% in the proximal and 10% in the distal third. The
      severity of the fracture and soft-tissue injury was greater with increasing
      injury severity. Less than 10% of the fractures were open. There was a bimodal
      age distribution with a peak in the third decade as a result of moderate to
      severe injury in men and a larger peak in the seventh decade after a simple fall
      in women.

PMID- 9546455
TI  - Vascular injuries in compound fractures of the leg with initially adequate
      circulation.
AB  - We carried out a randomised, controlled trial in 157 patients who had isolated
      severe Gustilo type-IIIa and type-IIIb fractures of the metaphysis or diaphysis
      of the leg to determine the prevalence of vascular injuries and the role of
      vascular repair. All patients had stable vital signs and clinically adequate
      circulation in their legs before operation. In a control group of 64 patients we
      performed conventional surgery with systematic debridement and primary
      stabilisation of the fractures. In the trial group of 93 patients the major
      vessels and nerves adjoining the compound fracture were routinely explored and
      repaired when necessary after the initial procedure. Two of the 28 control
      patients (7.1%) with type-IIIb compound fractures had signs of inadequate
      circulation after the first operation. Both had major vascular injuries which
      were demonstrated at a second procedure. In the trial group, major vascular
      injuries were found in two of 54 patients (3.7%) with type-IIIa and 11 of 39
      patients (28.2%) with type-IIIb compound fractures. Compared with the control
      group the trial group showed improved results at both the immediate and long-term
      follow-up. Routine exploration and early repair of injured major vessels of the
      leg in severe compound fractures gave encouraging results.

PMID- 9546456
TI  - Indomethacin versus radiation therapy for prophylaxis against heterotopic
      ossification in acetabular fractures: a randomised, prospective study.
AB  - We report a prospective, randomised, blinded clinical comparison of the use of
      indomethacin or radiation therapy for the prevention of heterotopic ossification
      (HO) in 75 adults who had open reduction and internal fixation of acetabular
      fractures through either a Kocher-Langenbeck, a combined ilioinguinal and Kocher
      Langenbeck, or an extended iliofemoral approach. Indomethacin, 25 mg, was given
      three times daily for six weeks. Radiation with 800 cGy was delivered within
      three days of operation. Plain radiographs were reviewed and given Brooker
      classification scores by three independent observers who were unaware of the
      method of prophylaxis. One patient died from unrelated causes and two were lost
      to follow-up, leaving 72, 33 in the radiation group and 39 in the indomethacin
      group, available for evaluation at a mean of 12 months (6 to 48). There was no
      significant difference in the two groups in terms of age, gender, injury severity
      score, estimated blood loss, delay to surgery, head injury, presence of femoral
      head dislocation, or operating time, and no complications due to either method of
      treatment. The final extent of HO was already present by six weeks in all
      patients who were followed up. Three patients in the radiation group and five who
      received indomethacin developed HO of Brooker grade III. Two patients in the
      indomethacin group developed Brooker IV changes; both had failed to receive
      proper doses of the drug. Cochran-Armitage analysis showed no significant
      difference between the two treatment groups as regards the formation of HO.
      Indomethacin and single-dose radiation therapy are both safe and effective for
      the prevention of HO after operation for acetabular fractures. Radiation therapy
      is, however, approximately 200 times more expensive than indomethacin therapy at
      our institution and has other risks.

PMID- 9546457
TI  - Pelvic insufficiency fracture with diastasis of the pubic symphysis after
      irradiation: a case report.
AB  - A 61-year-old woman was seen with diastasis of the symphysis pubis and
      insufficiency fractures of the wings of both ilia after irradiation for carcinoma
      of the cervix. The characteristics and treatment of these fractures are
      discussed.

PMID- 9546459
TI  - Stem fixation in the Charnley low-friction arthroplasty in young patients using
      an intramedullary bone block.
AB  - We report a prospective study of the use of intramedullary bone blocks to improve
      the fixation of a matt-finish femoral stem in Charnley low-friction
      arthroplasties. There were 379 patients (441 hips), but at a minimum follow-up of
      ten years there were 258 arthroplasties in 221 patients including some which had
      been revised. The mean age at surgery was 41 years (17 to 51) and the mean follow
      up was 13.4 years (1 to 20 including the early revisions). Nine stems (3.5%) had
      been revised for aseptic loosening, but there were no stem fractures.
      Survivorship of stems was 99.2% at ten years and 94.35% at 15 and 20 years. We
      found that the patient's gender, the position of the stem and the experience of
      the surgeon all influenced the outcome. Our findings suggest that using our
      method of stem fixation, follow-up of over 11 years was needed to reveal the
      effects of endosteal cavitation of the femur, and of over 13 years to assess any
      divergence between the clinical and the radiological outcomes of stem fixation.

PMID- 9546458
TI  - Severe osteolysis after third-body wear due to hydroxyapatite particles from
      acetabular cup coating.
AB  - One concern about the fixation of HA-coated implants is the possible
      disintegration of the surface, with the migration of HA granules into the joint
      space, producing third-body wear. We report a study of six revisions of HA-coated
      polyethylene RM cups at 9 to 14 years after successful primary arthroplasty. In
      all six hips, we found HA granules embedded in the articulating surface of the
      polyethylene, with abrasive wear of the cup and the metal femoral head. The cup
      had loosened in four hips and three showed severe osteolysis of the proximal
      femur. Third-body wear due to HA particles from implant coating may produce
      severe clinical problems with few early warning signs. Further clinical,
      radiological and histological observations are needed to determine the possible
      incidence of this late complication in the various types of coating of a variety
      of substrates.

PMID- 9546460
TI  - Diagnostic value of intra-articular anaesthetic in primary osteoarthritis of the
      hip.
AB  - We investigated 42 patients who were being considered for primary total hip
      arthroplasty (THA), but in whom it was uncertain whether the hip was the source
      of their pain. They were given an injection of local anaesthetic into the joint
      space. Of 33 patients who gained pain relief from their injection, 32
      subsequently had successful THA. The remaining patient has not had surgery. The
      intra-articular injection of local anaesthetic is thus at least 96% sensitive. Of
      the nine patients who had no or only minimal pain relief from injection, one has
      had an unsuccessful THA, three have been successfully treated for other
      conditions and five have unresolved pain for which no organic basis has been
      established. We believe that the injection of local anaesthetic into the hip is a
      reliable test, with low morbidity. In difficult cases it will aid in the
      clarification of the cause of pain which possibly arises from the hip.

PMID- 9546461
TI  - Retrograde nailing of femoral fracture below a hip prosthesis: a case report.
AB  - In a frail elderly patient a pathological fracture of the femur at the lower end
      of a loose femoral stem was treated by the retrograde insertion of an
      intramedullary nail over the tip of the prosthesis.

PMID- 9546462
TI  - Function of reinserted abductor muscles after femoral replacement.
AB  - We compared two methods of reconstruction of the abductor mechanism in 15
      patients after prosthetic replacement of the upper femur, to assess abductor
      strength and function. Six patients in group I had direct fixation of the gluteus
      medius tendon and a segment of the original bone to the prosthesis. Nine patients
      in group 2 had the abductor tendon fixed to the iliotibial band. We assessed
      clinical function, isometric muscle strength and muscle cross-sectional area for
      each patient. The patients in group 1 had better clinical and functional results
      (p = 0.059), with average peak torques for hip abduction of 92% of that in the
      non-operated leg in group 1, and of 57% in group 2. Group 1 had a mean muscle
      cross-sectional area of 69% and a mean value of strength per cross-sectional area
      of 134% when compared with the control side. The respective values for group 2
      were 52% and 91%. Direct fixation of the abductor muscles to the prostheses gave
      improved function and higher isometric abductor muscle force.

PMID- 9546463
TI  - Endoscopic reconstruction for isolated anterior cruciate ligament rupture.
AB  - We treated 90 patients with an isolated injury to the anterior cruciate ligament
      (ACL) by reconstruction using a patellar tendon autograft and interference screw
      fixation. Of these, 82 (91%) were available for review at 24 months. Two grafts
      and two contralateral ACLs had ruptured during sport and there was one case of
      atraumatic graft resorption. Using the assessment of the International Knee
      Documentation Committee (IKDC), 86% of the remaining patients were normal or
      nearly normal. The median Lysholm knee score was 95/100 and 84% of patients were
      participating in moderate to strenuous activity. All had grade-0 or grade-1
      Lachman, pivot-shift and anterior-drawer tests. Measurement with the KT1000
      arthrometer gave a side-to-side difference of <3 mm of anterior tibial
      displacement in 90%. Sixty-six radiographs were IKDC grade A and one was grade B.
      Pain on kneeling was present in 31% and graft site pain in 44%. At 24 months
      after operation all patients had excellent knee stability, a high rate of return
      to sport and minimal radiological evidence of degenerative change. Our series
      therefore represents a basis for comparison of results using other techniques and
      after more severe injuries.

PMID- 9546464
TI  - Fixation of the tibial component of total knee arthroplasty after high tibial
      osteotomy: a matched radiostereometric study.
AB  - To assess migration of the tibial component we used roentgen
      stereophotogrammetric analysis in 40 patients who had had a total knee
      arthroplasty after failure of a closing wedge osteotomy and compared them with 40
      matched patients after primary total knee arthroplasty. We found no difference in
      migration over time or in the tendency for continuous migration between the two
      groups. There were no differences in alignment or position of the knee prosthesis
      or in the clinical outcome. Our findings show that revision of a failed high
      tibial osteotomy to a total knee arthroplasty is effective.

PMID- 9546465
TI  - Lipoma arborescens of the knee.
AB  - Lipoma arborescens is a rare intra-articular lesion, characterised by diffuse
      replacement of the subsynovial tissue by mature fat cells, producing prominent
      villous transformation of the synovium. The aetiology of this benign condition is
      unknown. We describe six cases involving the knee, discussing the symptoms,
      diagnosis and treatment.

PMID- 9546466
TI  - Is there a future for hinged prostheses in primary total knee arthroplasty? A 20
      year survivorship analysis of the Blauth prosthesis.
AB  - The Blauth prosthesis is a hinged total knee replacement. We have evaluated 422
      consecutive primary total knee arthroplasties using this design in 330 patients
      with a maximum follow-up of 20 years (mean 6). The mean age of the patients at
      the time of operation was 70 years (29 to 87). Using endpoints of infection,
      removal because of aseptic loosening, removal for any cause, and the worst case
      as definitions of failure, the cumulative rates of survival at 20 years were
      93.6%, 96.0%, 94.4% and 86.8%, respectively. The cumulative rate of survival of
      the patients themselves was 14.4% (24% in patients with osteoarthritis and 9% in
      these with rheumatoid arthritis) after 20 years. Our survivorship analysis shows
      that hinged knee prostheses, when they are biomechanically well designed, can
      yield a satisfactory long-term outcome, similar to those of the best prostheses
      of the resurfacing type. Hinged knee prostheses continue to be of value in
      patients with severe deformity or instability of the knee.

PMID- 9546467
TI  - Prognosis in Perthes' disease: a comparison of radiological predictors.
AB  - We compared the prognostic value of the Catterall grouping, the Salter-Thompson
      grading, the arthrographic shape of the femoral head, and the Herring lateral
      pillar grouping during the fragmentation stage of Perthes' disease in 73 patients
      with 81 affected hips. Radiographs were available for study from the onset of the
      disease until skeletal maturity. We used the Stulberg classification to assess
      outcome. The Herring grade and arthrographic sphericity proved to be the best
      predictors of final outcome. Combining these two values further increased the
      predictive value. All but one patient in Herring group A achieved an excellent
      outcome. In Herring group B, the age of the child and the sphericity of the
      femoral head influenced the end result. If the child was less than seven years
      old at the onset of symptoms the prognosis was invariably good and all spherical
      hips in group B had a good outcome with Stulberg grades 1 or 2. Moderately and
      severely deformed hips on arthrography resulted in Stulberg 3 and 4 hips. None of
      the hips in Herring group C had a normal appearance at maturity and the outcome
      was not significantly influenced by the age at onset or the arthrographic
      appearance.

PMID- 9546468
TI  - Development of the hip in diastrophic dysplasia.
AB  - We examined 50 patients with diastrophic dysplasia both clinically and
      radiologically. Two legally aborted fetuses were dissected. The mean age of the
      patients was 16.2 years (newborn to 38) and the mean follow-up was 11.4 years (3
      months to 34 years). The fetal hips and MRI of newborn infants showed congruity
      and no significant joint deformity. Flexion contracture of the hip became evident
      later in 93% and was progressive. The radiological appearance of the proximal
      femoral ossific nuclei was delayed and in 17% of males and 28% of females the
      ossific nuclei had not appeared by the age of 12 years. Radiological measurements
      differed considerably from reference values and were related to the rapid and
      progressive restriction of rotational movement and the increase in flexion
      contracture. The typical findings were flattening and inferomedial bulking of the
      femoral head and a double-hump deformation. The changes in the hip led to
      secondary osteoarthritis before early middle age. We describe the clinical and
      radiological measurements which define the early degeneration of the joint.

PMID- 9546469
TI  - Ultrasonography of the hip in developmental hip dysplasia.
AB  - Ultrasonography of the hip was performed sequentially by two different examiners
      in 75 infants. The ultrasound strips were reviewed twice by three paediatric
      orthopaedic surgeons and classified by the Graf method. The intraobserver and
      interobserver agreement between the interpretations was analysed using simple and
      weighted kappa coefficients calculated for agreement on the Graf classification
      and for grouping as normal (types 1A to 2A), and abnormal requiring treatment
      (types 2B to 4). When examining the same ultrasound strip, intraobserver
      agreement for the Graf classification was substantial (mean kappa 0.61), but
      interobserver agreement was only moderate (kappa 0.50). For the grouping into
      normal and abnormal, the mean kappa value for intraobserver agreement was 0.67
      and for interobserver agreement 0.57. Because of the significant differences in
      agreement between normal and abnormal hips, we analysed a subgroup of those with
      at least one abnormal interpretation. Intraobserver agreement within this
      subgroup showed moderate reliability (kappa 0.41), but interobserver agreement
      was only fair (kappa 0.28). Interpretations of two different strips performed
      sequentially showed significantly lower agreement with an intraobserver kappa
      value of 0.29 and an interobserver value of 0.28. In the subgroup with at least
      one abnormal reading, the intraobserver kappa was 0.09 and the interobserver 0.1.
      Our findings suggest that both the technique of performing ultrasonography and
      the interpretation of the image may influence the result.

PMID- 9546470
TI  - The Singapore operation for recurrent dislocation of peroneal tendons: long-term
      results.
AB  - Recurrent dislocation of peroneal tendons is uncommon and there are few reports
      of the long-term results after repair. The Singapore operation, first described
      in 1985, is an anatomical repair based on the Bankart-like lesion seen in the
      superior peroneal retinaculum. We reviewed 21 patients after a mean follow-up of
      9.3 years, and found no recurrence. Eighteen had good functional results and had
      returned to their previous levels of vocational and sports activities. The three
      fair results were due to painful scars or neuromas.

PMID- 9546471
TI  - Ankle arthroplasty for rheumatoid arthritis and osteoarthritis: prospective long
      term study of cemented replacements.
AB  - We performed 52 cemented ankle arthroplasties for painful osteoarthritis (OA)
      (25) or rheumatoid arthritis (RA) (27) using an ankle prosthesis with a near
      anatomical design. We assessed the patients radiologically and clinically for up
      to 14 years using an ankle scoring system. The preoperative median scores were 29
      for the OA group and 25 for the RA group and at ten years were 93.5 and 83,
      respectively. Six ankles in the OA group and five in the RA group required
      revision or arthrodesis. Survivorship analysis of the two groups showed no
      significant differences with 72.7% survival for the OA group and 75.5% for the RA
      group at 14 years.

PMID- 9546472
TI  - Osteoarthritis of the ankle after foreign-body reaction to absorbable pins and
      screws: a three- to nine-year follow-up study.
AB  - Between 1985 and 1994, 1223 patients with malleolar fractures of the ankle were
      treated by open reduction and internal fixation with absorbable pins and screws,
      of whom 74 (6.1%) had an obvious inflammatory foreign-body reaction to the
      implants. Of these 74, ten later developed moderate to severe osteoarthritis of
      the ankle despite no evidence of incongruity of the articular surface. The
      implants used in these patients were made from polyglycolide, polylactide or
      glycolide-lactide copolymer. The joint damage seemed to be due to polymeric
      debris entering the articular cavity through an osteolytic extension of an
      implant track. The ten patients had a long clinical course which included a
      vigorous local foreign-body reaction, synovial irritation and subsequent
      degeneration. At a follow-up of three to nine years, ankle arthrodesis had been
      necessary in two patients and is being considered for another two. The incidence
      of these changes in the whole series was 0.8%, which is not high, but awareness
      of this possible late complication is essential.

PMID- 9546473
TI  - Quantitative comparison of wear debris from UHMWPE that has and has not been
      sterilised by gamma irradiation.
AB  - Ultra-high-molecular-weight polyethylene (UHMWPE) components for total joint
      replacement generate wear particles which cause adverse biological tissue
      reactions leading to osteolysis and loosening. Sterilisation of UHMWPE components
      by gamma irradiation in air causes chain scissions which initiate a long-term
      oxidative process that degrades the chemical and mechanical properties of the
      polyethylene. Using a tri-pin-on-disc tribometer we studied the effect of ageing
      for ten years after gamma irradiation in air on the volumetric wear, particle
      size distribution and the number of particles produced by UHMWPE when sliding
      against a stainless-steel counterface. The aged and irradiated material produced
      six times more volumetric wear and 34 times more wear particles per unit load per
      unit sliding distance than non-sterilised UHMWPE. Our findings indicate that
      oxidative degradation of polyethylene after gamma irradiation in air with ageing
      produces more wear.

PMID- 9546474
TI  - Wear in uncemented porous and cemented polyethylene sockets: a randomised,
      radiostereometric study.
AB  - We used radiostereometric analysis to compare wear rates between uncemented
      porous sockets and cemented all-polyethylene sockets in a series of 102 hips
      randomised for either a Harris-Galante or a Charnley cup. Wear was evaluated in
      95 hips at a mean of five years (2 to 7). All hips had a cemented, 22 mm head
      mono-bloc Charnley stem. The mean annual wear rate was 0.09 mm in the Charnley
      sockets and 0.10 mm in the Harris-Galante sockets, with no statistically
      significant differences in wear, migration or rotation. We conclude that, up to
      five years, the wear characteristics of the modular and porous Harris-Galante
      socket resemble that of the Charnley socket.

PMID- 9546475
TI  - Interbody cage stabilisation in the lumbar spine: biomechanical evaluation of
      cage design, posterior instrumentation and bone density.
AB  - We performed a biomechanical study on human cadaver spines to determine the
      effect of three different interbody cage designs, with and without posterior
      instrumentation, on the three-dimensional flexibility of the spine. Six lumbar
      functional spinal units for each cage type were subjected to multidirectional
      flexibility testing in four different configurations: intact, with interbody
      cages from a posterior approach, with additional posterior instrumentation, and
      with cross-bracing. The tests involved the application of flexion and extension,
      bilateral axial rotation and bilateral lateral bending pure moments. The relative
      movements between the vertebrae were recorded by an optoelectronic camera system.
      We found no significant difference in the stabilising potential of the three cage
      designs. The cages used alone significantly decreased the intervertebral movement
      in flexion and lateral bending, but no stabilisation was achieved in either
      extension or axial rotation. For all types of cage, the greatest stabilisation in
      flexion and extension and lateral bending was achieved by the addition of
      posterior transpedicular instrumentation. The addition of cross-bracing to the
      posterior instrumentation had a stabilising effect on axial rotation. The bone
      density of the adjacent vertebral bodies was a significant factor for
      stabilisation in flexion and extension and in lateral bending.

PMID- 9546476
TI  - Health status after Ilizarov reconstruction of post-traumatic lower-limb
      deformity.
AB  - Previous studies of the Ilizarov procedure have concentrated on musculoskeletal
      assessments rather than the opinions of patients. In a prospective trial of 25
      consecutive patients, we evaluated the effect of Ilizarov reconstruction of post
      traumatic deformity on general health status using the SF36 and Nottingham Health
      Profile (NHP). The patients had very low preoperative scores, which remained low
      during treatment and correction, but increased postoperatively. The mean overall
      SF36 score improved from 36 +/- 3 to 58 +/- 7 (p = 0.031) and the NHP score from
      39 +/- 11 to 67 +/- 10 (p = 0.002). The improvements in scores were not limited
      to the physical components and were equal or better than the improvements
      reported for other orthopaedic procedures, including total joint arthroplasty.
      Ilizarov-type reconstruction of deformity of the lower limb not only restores
      bony configuration, but also produces a large improvement in the general health
      status of patients.

PMID- 9546477
TI  - Laser Doppler flowmetry in the diagnosis of chronic compartment syndrome.
AB  - Chronic compartment syndrome (CCS) is usually considered to be due to ischaemia
      of muscle. We have attempted to use the direct measurement of muscle blood flow
      for diagnosis since the assessment of intracompartmental pressure does not
      provide accurate knowledge of the vascular state. We recorded simultaneously
      continuous measurements of the laser Doppler flow (LDF) in muscle and the
      intracompartment pressure (ICP) after exercise in seven patients with CCS, and in
      seven control subjects. The mean ICP was 74.1 +/- 4.4 mmHg in CCS patients and
      24.2 +/- 3.4 mmHg in control subjects one minute after exercise, decreasing to
      34.6 +/- 2.3 mmHg and 15.0 +/- 1.6 mmHg at 20 min, respectively. The LDF was 0.80
      +/- 0.11 arbitrary units (AU) in control subjects and 1.09 +/- 0.14 AU in CCS
      patients one minute after exercise, and 0.41 +/- 0.11 AU and 0.27 +/- 0.04 AU,
      respectively, at the end of the recovery period. The ICP showed a progressive
      decrease over time in both groups. The LDF decreased sharply during the first
      minutes of recovery in control subjects, but in patients with CCS there was a
      delayed hyperaemic peak with blood flow reaching 0.84 +/- 0.10 AU at nine minutes
      as against 0.33 +/- 0.06 AU for control subjects (p < 0.01). The ICP increased in
      both control subjects and CCS patients after exercise with no clear cut-off point
      between the groups. By contrast, changes in muscle blood flow over time were
      clearly different between control subjects and patients with CCS. For this
      reason, LDF should be investigated further as a technique for the diagnosis of
      CCS.

PMID- 9546478
TI  - Recurrence of giant-cell tumour of bone after the use of cement.

PMID- 9546480
TI  - MRI can prevent unnecessary arthroscopy.

PMID- 9546479
TI  - Thromboprophylaxis and death after total hip replacement.

PMID- 9546481
TI  - MRI can prevent unnecessary arthroscopy.

PMID- 9546482
TI  - MRI can prevent unnecessary arthroscopy.

PMID- 9546483
TI  - Early tourniquet release during total knee arthroplasty.

PMID- 9546484
TI  - Alternative treatments for meniscal injuries.

PMID- 9546485
TI  - The role of electromyography in neurology.
AB  - A review is given of the role of electromyography (EMG) for diagnosis,
      pathophysiological description and monitoring of patients with disorders of the
      peripheral nervous system. Various EMG methods are presented and their principal
      differences are discussed. The usefulness of these methods varies depending on
      the pathology to be studied. With modern quantitative methods for analysis, EMG
      has become more sensitive and accurate and is therefore an important part in the
      evaluation of the neurologic patient. EMG results are usually combined with
      findings from other neurophysiological investigations (neurography, evoked
      potentials), histochemistry, biochemistry and most importantly with the clinical
      signs to give as complete a picture of the condition as possible. The usefulness
      of EMG depends on a number of factors other than the quality of the investigation
      as such. These aspects are discussed briefly.

PMID- 9546486
TI  - The largest Lyapunov exponent of the EEG during ECT seizures as a measure of ECT
      seizure adequacy.
AB  - Attributes of the electroencephalogram (EEG) recorded during electroconvulsive
      therapy (ECT) seizures appear promising for decreasing the uncertainty that
      exists about how to define a therapeutically adequate seizure. In the present
      report we study whether one promising and not yet tested ictal EEG measure, the
      largest Lyapunov exponent (lambda1), is useful in this regard. We calculated
      lambda1 from 2 channel ictal EEG data recorded in 25 depressed subjects who
      received right unilateral ECT. We studied the relationship of lambda1 to
      treatment therapeutic outcome and to an indirect measure of treatment therapeutic
      potency, the extent to which the stimulus intensity exceeds the seizure
      threshold. We found lambda1 could be reliably calculated from ictal EEG data and
      that the global mean, maximum, and standard deviation of lambda1 were smaller in
      the more therapeutically potent moderately suprathreshold ECT and in therapeutic
      responders. These results imply a more predictable or consistent pattern of EEG
      seizure activity over time in more therapeutically effective ECT seizures. These
      findings also suggest the promise of lambda1 as a marker of ECT seizure
      therapeutic adequacy and build on our previous work suggesting that lambda1 may
      be useful for classifying seizures and for reflecting the relative physiologic
      impact of seizure activity.

PMID- 9546488
TI  - Neurophysiologic surgical monitoring staffing patterns in the USA.
AB  - Staffing patterns for intraoperative EEG and somatosensory evoked potential
      monitoring were assessed in a survey of 150 US board certified clinical
      neurophysiologists. Whether or not a clinical neurophysiology physician needs to
      be in the operating room throughout monitoring has been a point of disagreement
      and debate. The data here provide evidence that most US clinical
      neurophysiologists send non-physician staff to monitor EEG during carotid
      endarterectomies. Similar results were found for somatosensory evoked potential
      spinal cord monitoring during scoliosis procedures. By describing current
      staffing practices, these data can promote a more informed debate on this
      controversial topic.

PMID- 9546487
TI  - Early detection of vasospasm after acute subarachnoid hemorrhage using continuous
      EEG ICU monitoring.
AB  - The neurologic morbidity of delayed ischemic deficits from vasospasm following
      aneurysmal subarachnoid hemorrhage (SAH) continues to be the most debilitating
      complication from this devastating illness. Neurologic critical care is focused
      on recognition and treatment of these secondary insults but often the treatment
      is withheld until an irreversible deficit becomes manifest. Continuous EEG (cEEG)
      monitoring provides a unique potential to recognize early secondary insults and
      offers an opportunity for early intervention. We studied 32 SAH patients using
      cEEG and trending of the quantitative measure, relative alpha (RA), to determine
      if reductions in RA variability occurred with documented vasospasm. In 19/19
      patients with angiographically documented vasospasm, we found that RA variability
      was decreased by a mean of two grades and improved with resolution of vasospasm.
      In 10/19 this reduction in RA variability preceded the diagnosis of vasospasm by
      a mean of 2.9 days (SD 1.73). The positive predictive and negative predictive
      values are 76% and 100%, respectively. Non-diagnostic clinical signs at the time
      of RA variability reduction and vasospasm were present in 12/19 patients. Thus
      decreased RA variability is able to provide early detection of neurologic
      complications such as vasospasm in patients before clear clinical symptoms and
      signs occur.

PMID- 9546489
TI  - Dynamics of EEG background activity level during quiet sleep in multiple
      nocturnal sleep episodes in infants.
AB  - The study reported in this paper investigated the dynamics of EEG background
      activity during quiet sleep (QS) in the first year of life. These dynamics have
      been previously shown to follow an intra-sleep trend within a single sleep
      episode, and the aim of this study was to show whether they were similar in two
      successive nocturnal sleep episodes interrupted by a waking episode, or whether
      they exhibited a progressive trend across the two episodes. The polygraphic
      recordings of two groups of 6 infants aged from 9 to 15 weeks old and from 25 to
      47 weeks old, whose nocturnal sleep organisation was spontaneously interrupted,
      were selected. Three indicators of the time course of the parameter value,
      obtained from automatic analysis and reflecting the degree of synchronisation of
      the EEG activity recorded by the centro-occipital lead, were computed for the
      first two QS periods of two successive sleep episodes: the parameter range
      (difference between the EEG parameter value at the QS onset and that at the
      trough); the trough latency (time interval between QS onset and trough); and rate
      of synchronisation (range/trough latency). All 3 indicators differed between the
      first and the second QS period of both sleep episodes independently of age. The
      rate of synchronisation (but not the parameter range and the trough latency) was
      higher in the first sleep episode than in the second one, showing an over-night
      decreasing trend. Those results show that, when nocturnal sleep in infants is
      split into two episodes separated by an intervening waking, also the second sleep
      episode displays an internal organisation of its EEG dynamics. Moreover, an
      across-night trend in the rate of synchronisation can be observed from an early
      age, a finding which suggests, again, the early emergence of homeostatic
      regulation of sleep.

PMID- 9546490
TI  - Relationship between muscle tone changes, sawtooth waves and rapid eye movements
      during sleep.
AB  - 'Sawtoothed' waves occur during rapid eye movement (REM) sleep, but their source
      as well as their function is not known. We studied the onset of sawtooth waves
      (STW) in relation to the onset of muscle tone reduction (MTR) and to REM during
      20 polysomnographic recordings in 11 normal volunteers. Seventy-seven (85%) of a
      total of 91 REM sleep cycles were used for further analysis, because within a
      1000 s interval they showed a relatively stereotyped sequence of events: a
      generalized body movement, followed by MTR, then the appearance of STW, and
      ending with the first REM. The first STW often occurred during the electrographic
      stage II period prior to the beginning of the REM, by which time muscle tone was
      either already at or close to the tone level of the REM sleep period in all
      subjects. The overall mean onset time of MTR was 267 s (range 89-660 s), STW was
      378 s (range 169-779), and REM was 448 s (range 265-849); their differences were
      highly significant (F = 27.1, df 2,20, P < 0.001). Our data suggest that a
      predictable sequence of muscle tone reduction, then STW, and then REM, precedes
      the generally accepted onset of the REM sleep period, and may have implications
      for the redesignation of physiologic REM sleep onset.

PMID- 9546491
TI  - Auto power and coherence analysis of delta-theta band EEG during the waking
      sleeping transition period.
AB  - To evaluate the spatio-temporal variation of delta and theta band EEGs during the
      waking-sleeping transition period, auto power and coherence analyses of scalp
      EEGs were carried out on 12 male subjects. The 7 auto power and 21 coherence
      values obtained from the 7 areas were studied every 20 s from 5 min before stage
      1 onset to 24 min after stage 1 onset. The consecutive samples of spectra were
      computed for two frequency bands (delta: 2.5-3.5 Hz; theta: 4.0-7.5 Hz). Auto
      power started to increase after stage 1 onset and terminated 8.4 min after stage
      2 onset. Topograms of each band power changed with progression towards deep sleep
      from the flat or relatively low voltage pattern without any focus to the
      frontopolar-parietal pattern or the fronto-parietal dominant pattern. Principal
      component analysis of the coherence values revealed generalized and localized
      components in each band. The generalized component was distributed across scalp
      areas, while the localized component was distributed in frontopolar-frontal
      areas. The generalized component decreased to the plateau level of non-rapid eye
      movement (NREM) sleep 5.4 min after stage 2 onset. The localized component
      started to increase after stage 1 onset and reached the plateau level of NREM
      sleep 2.4 min after stage 2 onset. These results indicate that the delta-theta
      band EEG structures of the waking-sleeping transition period may not be uniform
      across the scalp areas and the hypnagogic period may start after stage 1 onset
      and continue for 8.4 min after stage 2 onset.

PMID- 9546492
TI  - EEG-based discrimination between imagination of right and left hand movement.
AB  - Three subjects were asked to imagine either right or left hand movement depending
      on a visual cue stimulus. The interval between two consecutive imagination tasks
      was > 10 s. Each subject imagined a total of 160 hand movements in each of 3-4
      sessions (training) without feedback and 7-8 sessions with feedback. The EEG was
      recorded bipolarly from left and right central and parietal regions and was
      sampled at 128 Hz. In the feedback sessions, the EEG from both central channels
      was classified on-line with a neural network classifier, and the success of the
      discrimination between left and right movement imagination was given within 1.5 s
      by means of a visual feedback. For each subject, different frequency components
      in the alpha and beta band were found which provided best discrimination between
      left and right hand movement imagination. These frequency bands varied between 9
      and 14 Hz and between 18 and 26 Hz. The accuracy of on-line classification was
      approximately 80% in all 3 subjects and did not improve with increasing number of
      sessions. By averaging over all training and over all feedback sessions, the EEG
      data revealed a significant desynchronisation (ERD) over the contralateral
      central area and synchronisation (ERS) over the ipsilateral side. The ERD/ERS
      patterns over all sessions displayed a relatively small intra-subject variability
      with slight differences between sessions with and without feedback.

PMID- 9546493
TI  - Reproducibility and validity of electric source localisation with high-resolution
      electroencephalography.
AB  - The present study investigates the reproducibility and validity of the EEG source
      localisation of somatosensory evoked potentials (SEPs) using high-resolution EEG
      (61 scalp electrodes) and a source reconstruction on the basis of the individual
      brain morphology as obtained from magnetic resonance images (MRIs). The
      somatosensory evoked potentials (SEPs) to electrical stimulation of the right
      median nerve were repeatedly collected from the scalp of one healthy subject in 9
      replications run on 9 different days. The source reconstruction for the 19 ms SEP
      component was performed by using a single moving dipole model as a source model.
      Two different head models were used: a spherical 3 shell model and a more
      realistically shaped 3 compartment model computed using the boundary element
      method (BEM). The source locations of the 19 ms SEP component were found to be
      highly reproducible using both head models: the mean standard deviation of the
      dipole locations was found to be 2.6 mm for the 3 shell model and 4 mm for the
      more realistically shaped head model. By projection into the individual MRI, the
      dipoles resulting from either head models were found to be located within the
      postcentral gyrus. The electric source locations were consistent with the maximum
      of the task-specific changes seen in a functional magnetic resonance imaging
      (fMRI) experiment when using the same somatosensory stimulation protocol.

PMID- 9546494
TI  - Bicoherence of intracranial EEG in sleep, wakefulness and seizures.
AB  - The hypothesis that the intracranial EEG has local structure and short-term non
      stationarity is tested with a little-studied measure of non-linear phase
      coupling, the bicoherence in human subdural and deep temporal lobe probe data
      from 11 subjects during sleeping, waking and seizure states. This measure of
      cooperativity estimates the proportion of energy in every possible pair of
      frequency components, F1, F2 (from 1 to 50 Hz in this study), that satisfies the
      definition of quadratic phase coupling (phase of component at F3, which is F1 +
      F2, equals phase of F1 + phase of F2). Derived from the bispectrum, which
      segregates the non-Gaussian energy, auto-bicoherence uses the frequency
      components in one channel; cross-bicoherence uses one channel for F1 and F2 and
      another for F3. These higher order spectra are used in physical systems for
      detection of episodes of non-linearity and transients, for pattern recognition
      and robust classification, relatively immune to Gaussian components and low
      signal to noise ratios. Bicoherence is found not to be a fixed character of the
      EEG but quite local and unstable, in agreement with the hypothesis. Bicoherence
      can be quite different in adjacent segments as brief as 1.6 s as well as adjacent
      intracranial electrodes as close as 6.5 mm, even when the EEG looks similar. It
      can rise or fall steeply within millimeters. It is virtually absent in many
      analysis epochs of 17s duration. Other epochs show significant bicoherence with
      diverse form and distribution over the bifrequency plane. Isolated peaks,
      periodic peaks or rounded mountain ranges are either widely scattered or confined
      to one or a few parts of the plane. Bicoherence is generally an invisible
      feature: one cannot usually recognize the responsible form of non-linearity or
      any obvious correlate in the raw EEG. During stage II/III sleep overall mean
      bicoherence is generally higher than in the waking state. During seizures the
      diverse EEG patterns average a significant elevation in bicoherence but have a
      wide variance. Maximum bispectrum, maximum power spectrum, maximum and mean
      bicoherence, skewness and asymmetry all vary independently of each other. Cross
      bicoherence is often intermediate between the two auto-bicoherence spectra but
      commonly resembles one of the two. Of the known factors that contribute to
      bicoherence, transient as distinct from ongoing wave forms can be more important
      in our data sets. This measure of non-linear higher moments is very sensitive to
      weak quadratic phase coupling; this can come from several kinds of waveforms. New
      methods are needed to evaluate their respective contributions. Utility of this
      descriptor cannot be claimed before more carefully defined and repeatable brain
      states are studied.

PMID- 9546495
TI  - Stimulus-evoked electrographic patterns in neonates: an abnormal form of
      reactivity.
AB  - Stimulus-evoked electrographic patterns are described for 12 neonates, coincident
      with tactile or painful stimulation. Four newborns had stimulus-evoked
      electrographic seizures with and without concomitant clinical seizure behaviors.
      Eight neonates had generalized or focal stimulus-evoked discharges, with or
      without coincident movements, which did not evolve into electrographic seizures.
      Nine infants were less than 36 weeks estimated gestational age at the time
      stimulus-evoked discharges were noted. Eleven neonates were comatose or
      phamacologically paralyzed at the time the stimulus-evoked patterns were
      initially noted. All neonates had moderate or severe interictal EEG background
      abnormalities at the time these patterns were observed. All patients had brain
      lesions documented by either cranial imaging or neuropathological examinations.
      Eleven patients died or have significant neurological handicaps. These phenomena
      represent an abnormal form of cortical reactivity to sensory stimuli in the
      developing brain. Most neonates with these patterns have significant diffuse or
      multifocal damage to the neocortex.

PMID- 9546497
TI  - Changing, from top to bottom.

PMID- 9546498
TI  - Pallidotomy for Parkinson's disease: hitting the target?

PMID- 9546496
TI  - Topographic distribution of seizure onset and hippocampal atrophy: relationship
      between MRI and depth EEG.
AB  - Medial temporal lobe epilepsy (MTLE) is associated with hippocampal cell loss and
      organization of the dentate gyrus. Some studies suggest a correlation between the
      topographic distribution of cell loss and site of epileptogenesis. We studied the
      relationship between the site of ictal onset with the presence of segmental
      atrophy in patients with non-lesional MTLE using magnetic resonance imaging (MRI)
      and depth EEG. Ictal recordings were obtained from 27 patients with longitudinal
      hippocampal depth electrodes and variable combinations of subdural strips
      sampling medial temporal structures. The location of the depth electrode contacts
      was correlated with anatomical landmarks. Seizures were analyzed for the
      distribution of onset along the long axis of the hippocampus. MRI analysis were
      performed to detect segmental atrophy. Outcome was assessed 1 year or more
      following anterior temporal lobectomy. Twenty-five patients had unilateral, and
      two had bilateral, hippocampal atrophy. One hundred and forty-seven seizures were
      reviewed: 21 showed focal onset and 126 showed regional onset. Ictal onset
      involved the amygdala and anterior half of the hippocampus in 80% of the seizures
      while only 40% of patients had atrophy of these segments. Most patients had
      excellent outcome. In patients with MTLE the primary area of epileptogenesis does
      not parallel the hippocampal segments with the greatest degree of volume loss.

PMID- 9546499
TI  - Electrovaporisation of the prostate.

PMID- 9546500
TI  - Vein quality in vascular surgery.

PMID- 9546501
TI  - Statins for prevention of stroke.

PMID- 9546502
TI  - Nomenclature of enterotoxins.

PMID- 9546503
TI  - Conditions in prisons.

PMID- 9546504
TI  - Continuing medical education: shibboleth or necessity?

PMID- 9546505
TI  - Randomised controlled trial of prophylactic antibiotics before insertion of
      intrauterine devices. IUD Study Group.
AB  - BACKGROUND: The value of antibiotic prophylaxis before insertion of an
      intrauterine device (IUD) remains uncertain. We undertook a triple-masked,
      randomised, placebo-controlled trial to find out whether such prophylaxis reduces
      the rate of IUD removal within 90 days. METHODS: 11 clinic sites in southern
      California enrolled women who requested IUD insertion and were at low risk of
      sexually transmitted infection according to self-reported medical history. We
      randomly assigned 1985 participants either 500 mg azithromycin or placebo
      capsules of identical appearance taken about 1 h before insertion of a Copper T
      380A IUD. 118 women did not have an IUD inserted. We followed up 1833 of the
      remaining 1867 (98%) participants for at least 90 days after insertion. FINDINGS:
      The rate of IUD removal for any reason other than partial expulsion was 3.8%
      (35/918) in the antibiotic group and 3.4% (31/915) in the placebo group (relative
      risk 1.1 [95% CI 0.7-1.8]). The two treatment groups sought medical attention
      with equal frequency (mean 38 visits per 100 women). During the 90 days after IUD
      insertion, only one woman from each assignment group had salpingitis, as defined
      by established criteria. INTERPRETATION: Prophylaxis with azithromycin did not
      affect the likelihood that a woman would retain her IUD at 90 days or the
      frequency of postinsertion medical attention. In appropriately screened women,
      the risk of upper-genital-tract infection is negligible after IUD insertion, with
      or without the administration of prophylactic antibiotics.

PMID- 9546506
TI  - Inequalities in self-rated health: explanations from different stages of life.
AB  - BACKGROUND: Inequalities in health are a major public-health concern. A greater
      understanding is needed on the relative importance of different causes. We
      investigated the contribution of risk factors identified at different life stages
      to inequalities in self-rated health. METHODS: We used data from 5606 men and
      5799 women in the 1958 British birth cohort followed-up to age 33 years, on
      health behaviour, education, adolescent health, family structure and social
      support, work characteristics, and material circumstances. We assessed the
      contribution of different factors to social-class differences in self-rated
      health by adjustment of odds ratios (classes IV and V vs I and II). FINDINGS:
      Odds ratios of poor-rated health at age 33 were 3.15 for men and 2.30 for women,
      which decreased to 2.06 and 1.34, respectively, after adjustment for previously
      identified factors from birth to early adulthood. Adjustment for adult work
      characteristics, material circumstances, and health behaviour between ages 23
      years and 33 years further decreased the odds ratios to 1.64 (men) and 1.11
      (women). Most factors contributed to the reduction in odds ratios, although
      adolescent socioemotional adjustment, class at birth, educational qualifications,
      and psychosocial job strain were especially important. Additional key factors for
      men were adult smoking and job insecurity, and for women, housing during
      childhood, adult income, and age at first child. INTERPRETATION: There was no
      single cause of health inequality at age 33 years. Explanations spanned from
      early life to young adulthood. Policy implications include reduction of social
      differences in material circumstances and of differences in individual skills and
      resources acquired in early life.

PMID- 9546507
TI  - Effects of resective surgery for left-sided intracranial tumours on language
      function: a prospective study.
AB  - BACKGROUND: Although language disorders occur in about 50% of patients with a
      left hemispheric tumour and are a significant cause of morbidity, the effects of
      resective neurosurgery and their relation to tumour pathology are unclear. We
      report the immediate effects of resective surgery on language functions in a
      heterogeneous group of patients with left-sided intracranial tumours. METHODS: 40
      patients were studied. The Western Aphasia Battery (WAB) and Boston Naming Test
      (BNT) were administered preoperatively and before discharge following resective
      neurosurgery. Dexamethasone dose at time of testing was recorded, as was time
      taken to complete the tests, and tumour neuropathology. FINDINGS: 15 patients
      with normal aphasia quotients and language quotients before resective surgery all
      had normal quotients postoperatively. 25 who were dysphasic (ie, aphasia quotient
      <93.8) preoperatively showed significant postoperative improvements in both their
      mean aphasia quotient (from 81.8 to 89.1, p=0.004) and their mean language
      quotient (from 73.4 to 85.4, p=0.001), though 13 remained dysphasic. Two of the
      25 dysphasic patients had their WAB scores lowered by tumour resection. The
      findings and postoperative changes in BNT scores were almost identical to the
      pattern of those in WAB scores. At second assessment, dexamethasone therapy was
      significantly (p<0.01) lower than preoperative dose (reduction from mean 10.3
      mg/day to 0.7 mg/day in the dysphasic group). Patients with glioblastoma were
      more likely to have lower aphasia quotients, language quotients, and BNT scores
      than patients with anaplastic glioma, metastasis, or meningioma. Although the
      glioblastoma group had the greatest improvements in WAB operative scores, 57%
      remained dysphasic after resective surgery. Two additional patients declined
      postoperative assessment. INTERPRETATION: Resective surgery for left-sided
      intracranial tumours significantly improves language function in dysphasic
      patients, and is unlikely to impair language functions in non-dysphasic patients.
      Dysphasia and its response to resective surgery are related to the tumour
      neuropathology.

PMID- 9546509
TI  - First-trimester transabdominal fetal echocardiography.
AB  - BACKGROUND: Fetal echocardiography is usually done during the second trimester of
      pregnancy, but waiting until that time can lead to anxiety for the parents if the
      fetus is at high risk of having cardiac abnormalities. We report the feasibility
      of transabdominal first-trimester fetal echocardiography for early reassurance of
      normality or a prenatal diagnosis of a cardiac malformation. METHODS: We did
      first-trimester fetal echocardiography and colour-flow mapping with a 5 MHz
      curvilinear transducer at 13 weeks' gestation (range 12-13+6 days) in 15 fetuses
      at risk of cardiac defects. The fetus was judged to be normal if the
      investigation showed normal visceral situs, four-chamber view, and two normally
      related great arteries of similar size. We did second-trimester scans and
      neonatal follow-up for the women who continued with their pregnancies; necropsy
      was done in two cases of pregnancy termination. FINDINGS: Ten fetuses had normal
      hearts at the time of the first scan, which was confirmed during second-trimester
      assessment. In one fetus, the four-chamber view was asymmetrical and a moderate
      sized apical muscular ventricular septal defect (VSD) was diagnosed after birth.
      In another two fetuses we diagnosed small muscular VSD on the second-trimester
      scans. A complex cardiac malformation was correctly diagnosed in one fetus at 12
      weeks of gestation. Thus, in 11 fetuses, the imaging was of sufficient quality to
      reassure the family or to diagnose an abnormality. In the other four fetuses, the
      investigation was judged to be incomplete, but no definite cardiac abnormality
      was identified. INTERPRETATION: Transabdominal fetal echocardiography in the
      first trimester of pregnancy is feasible. In most patients the resolution of
      images is sufficient to allow assessment of basic cardiac anatomy, when normal,
      or detection of complex malformations, when present.

PMID- 9546508
TI  - Risk factors for and prevention of sporadic infections with vero cytotoxin (shiga
      toxin) producing Escherichia coli O157.
AB  - BACKGROUND: Recent outbreaks of vero cytotoxin (shiga toxin) producing
      Escherichia coli O157 (VTEC O157) infection have stimulated debate on food
      safety. However, 90% of cases in England and Wales are sporadic. We report a case
      control study of sporadic VTEC O157 infection. METHODS: We compared 85 sporadic
      cases of VTEC O157 infection, identified through population surveillance, with
      142 controls, randomly selected from general practitioners' lists. We matched
      cases and controls for age, sex, and family doctor's practice. Exposures to
      foods, water, animals, farms, and environmental factors were recorded. We visited
      the premises concerned when cases had eaten beefburgers or cooked sliced meats
      from caterers or had had contact with a farm. FINDINGS: Consumption of a
      beefburger from a catering premises other than from a fast-food chain A (a
      national chain) and consumption of cold cooked sliced meat (eg, in a salad or
      sandwich) from caterers, but not butchers, was associated with VTEC O157
      infection (odds ratios 4.63 [95% CI 1.33-30.14] and 3.36 [1.04-12.74],
      respectively). Policies for ensuring thorough cooking of burgers by one national
      fast-food chain differed from the other catering premises we visited. There was
      evidence of person-to-person spread and transmission of VTEC O157 infection from
      animals. INTERPRETATION: Local inspection of catering establishments that serve
      cooked meats together with public education to prevent spread on farms and in
      houses would reduce the burden of VTEC O157 infection by about 10% for each risk
      factor.

PMID- 9546510
TI  - A brain haemorrhage?

PMID- 9546511
TI  - Intracerebral haemorrhage caused by drug abuse.

PMID- 9546512
TI  - Antiretrovirals during pregnancy in HIV-1-positive women in New York City.

PMID- 9546513
TI  - Outbreak of Legionnaires' disease at a bar after basement flooding.

PMID- 9546514
TI  - Aplastic anaemia during treatment with fluoxetine.

PMID- 9546515
TI  - Familial leg ulcers.

PMID- 9546516
TI  - Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer's disease.

PMID- 9546517
TI  - Increased urinary retinol loss in children with severe infections.

PMID- 9546518
TI  - Does the salmon patch reappear?

PMID- 9546519
TI  - ATLAS shows global undertreatment of heart failure.

PMID- 9546521
TI  - Meditating on yogic science.

PMID- 9546522
TI  - War surgery continues in Sri Lanka.

PMID- 9546523
TI  - "Disgust" at Canada's tainted-blood settlement.

PMID- 9546524
TI  - US court to rule whether HIV infection constitutes disability.

PMID- 9546526
TI  - Migraine.

PMID- 9546527
TI  - The oasis.

PMID- 9546528
TI  - Eating for two: are guidelines for weight gain during pregnancy too liberal?

PMID- 9546529
TI  - Highly active antiretroviral therapy.

PMID- 9546530
TI  - Highly active antiretroviral therapy.

PMID- 9546531
TI  - Highly active antiretroviral therapy.

PMID- 9546532
TI  - Highly active antiretroviral therapy.

PMID- 9546533
TI  - Highly active antiretroviral therapy.

PMID- 9546534
TI  - Highly active antiretroviral therapy.

PMID- 9546535
TI  - Septic arthritis.

PMID- 9546536
TI  - Septic arthritis.

PMID- 9546537
TI  - Magnesium sulphate in eclampsia.

PMID- 9546539
TI  - Meta-analyses, multivariate analyses, and coping with the play of chance.

PMID- 9546538
TI  - Magnesium sulphate in eclampsia.

PMID- 9546540
TI  - Biochemical detection of systolic dysfunction.

PMID- 9546541
TI  - Biochemical detection of systolic dysfunction.

PMID- 9546542
TI  - Lung transplantation.

PMID- 9546543
TI  - Maternal inheritance of longevity.

PMID- 9546544
TI  - Ethics review and clinical trials.

PMID- 9546545
TI  - Ethics review and clinical trials.

PMID- 9546546
TI  - Ethics review and clinical trials.

PMID- 9546547
TI  - Hyphenosis.

PMID- 9546548
TI  - Switching sides.

PMID- 9546549
TI  - A piece of my mind. The teaching case.

PMID- 9546550
TI  - Emerging infections on center stage at first major international meeting.

PMID- 9546551
TI  - Acne drug depression warnings highlight need for expert care.

PMID- 9546552
TI  - From the Centers for Disease Control and Prevention. Mortality among children
      with sickle cell disease identified by newborn screening during 1990-1994-
      California, Illinois, and New York.

PMID- 9546553
TI  - From the Centers for Disease Control and Prevention. HIV/AIDS among American
      Indians and Alaskan Natives--United States, 1981-1997.

PMID- 9546554
TI  - From the Centers for Disease Control and Prevention. Administration of zidovudine
      during late pregnancy and delivery to prevent perinatal HIV transmission-
      Thailand, 1996-1998.

PMID- 9546555
TI  - From the Centers for Disease Control and Prevention. Self-assessed health status
      and selected behavioral risk factors among persons with and without health-care
      coverage--United States, 1994-1995.

PMID- 9546556
TI  - Palliative options at the end of life.

PMID- 9546557
TI  - Palliative options at the end of life.

PMID- 9546558
TI  - Palliative options at the end of life.

PMID- 9546559
TI  - Palliative options at the end of life.

PMID- 9546560
TI  - Standards for scientific behavior and research integrity.

PMID- 9546561
TI  - Screening for cystic fibrosis.

PMID- 9546562
TI  - Screening for cystic fibrosis.

PMID- 9546563
TI  - Effect of vitamins C and E on vascular reactivity.

PMID- 9546564
TI  - Clinical Crossroads: a 73-year-old man with symptomatic benign prostatic
      hyperplasia.

PMID- 9546565
TI  - Prevalence of hearing loss among children 6 to 19 years of age: the Third
      National Health and Nutrition Examination Survey.
AB  - CONTEXT: Hearing loss in children influences the development of communication and
      behavioral skills, but few studies in the United States have used pure-tone
      audiometry to derive hearing loss prevalence estimates for children. OBJECTIVE:
      To describe the prevalence of hearing loss among US children by sociodemographic
      characteristics, reported hearing loss, and audiometric screening factors.
      DESIGN: National population-based cross-sectional survey with an in-person
      interview and audiometric testing at 0.5 to 8 kHz. SETTING/PARTICIPANTS: A total
      of 6166 children aged 6 to 19 years completed audiometry in the mobile
      examination center of the Third National Health and Nutrition Examination Survey
      conducted between 1988 and 1994. MAIN OUTCOME MEASURE: Hearing loss, defined as
      audiometric threshold values of at least 16-dB hearing level based on a low or
      high pure-tone average. RESULTS: A total of 14.9% of children had low-frequency
      or high-frequency hearing loss of at least 16-dB hearing level, 7.1% had low
      frequency hearing loss of at least 16-dB hearing level, and 12.7% had high
      frequency hearing loss of at least 16-dB hearing level. Most hearing loss was
      unilateral and slight in severity (16- to 25-dB hearing level). Of those with
      measured hearing loss, 10.8% were reported to have current hearing loss during
      the interview. CONCLUSIONS: This analysis indicates that 14.9% of US children
      have low-frequency or high-frequency hearing loss of at least 16-dB hearing level
      in 1 or both ears. Among children in elementary, middle, and high school,
      audiometric screening should include low-frequency and high-frequency testing to
      detect hearing loss.

PMID- 9546566
TI  - Preemptive epidural analgesia and recovery from radical prostatectomy: a
      randomized controlled trial.
AB  - CONTEXT: Preemptive analgesia can decrease the sensitization of the central
      nervous system that would ordinarily amplify subsequent nociceptive input, but a
      clear demonstration of its clinical efficacy is necessary for it to become a
      routine component of acute pain therapy. OBJECTIVE: To determine the impact of
      preemptive epidural analgesia on postoperative pain and other clinically
      important outcome variables after radical retropubic prostatectomy. DESIGN AND
      SETTING: A block randomized double-blind clinical trial lasting 20 months at a
      single academic medical center. PATIENTS: A total of 100 generally healthy and
      neurologically intact patients scheduled for radical retropubic prostatectomy for
      the treatment of prostate cancer in whom an epidural catheter for treating
      postoperative pain was to be placed prior to the induction of general anesthesia.
      INTERVENTIONS: Epidural bupivacaine, epidural fentanyl, or no epidural drug was
      administered prior to induction of anesthesia and throughout the entire
      operation, followed by aggressive postoperative epidural analgesia for all
      patients. MAIN OUTCOME MEASURES: Daily pain scores during hospitalization and
      pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge. RESULTS:
      The patients who received epidural fentanyl or bupivacaine prior to surgical
      incision (preemptive analgesia) experienced 33% less pain while hospitalized
      (P=.007). Pain scores in those receiving preemptive analgesia were significantly
      lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5
      weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were
      pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients
      receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01),
      but not at 5.5 or 9.5 weeks. CONCLUSIONS: Even in the presence of aggressive
      postoperative pain management, preemptive epidural analgesia significantly
      decreases postoperative pain during hospitalization and long after discharge, and
      is associated with increased activity levels after discharge.

PMID- 9546567
TI  - Visual processing impairment and risk of motor vehicle crash among older adults.
AB  - CONTEXT: Motor vehicle crash risk in older drivers has been associated with
      visual acuity loss, but only weakly so, suggesting other factors contribute. The
      useful field of view is a measure that reflects decline in visual sensory
      function, slowed visual processing speed, and impaired visual attention skills.
      OBJECTIVE: To identify whether measures of visual processing ability, including
      the useful field of view test, are associated with crash involvement by older
      drivers. DESIGN: Prospective cohort study with 3 years of follow-up, 1990-1993.
      SETTING: Ophthalmology clinic assessment of community-based sample. PATIENTS: A
      total of 294 drivers aged 55 to 87 years at enrollment. MAIN OUTCOME MEASURE:
      Motor vehicle crash occurrence. RESULTS: Older drivers with a 40% or greater
      impairment in the useful field of view were 2.2 times (95% confidence interval,
      1.2-4.1) more likely to incur a crash during 3 years of follow-up, after
      adjusting for age, sex, race, chronic medical conditions, mental status, and days
      driven per week. This association was primarily mediated by difficulty in
      dividing attention under brief target durations. CONCLUSION: Reduction in the
      useful field of view increases crash risk in older drivers. Given the relatively
      high prevalence of visual processing impairment among the elderly, visual
      dysfunction and eye disease deserve further examination as causes of motor
      vehicle crashes and injury.

PMID- 9546568
TI  - Issues in comparisons between meta-analyses and large trials.
AB  - CONTEXT: The extent of concordance between meta-analyses and large trials on the
      same topic has been investigated with different protocols. Inconsistent
      conclusions created confusion regarding the validity of these major tools of
      clinical evidence. OBJECTIVE: To evaluate protocols comparing meta-analyses and
      large trials in order to understand if and why they disagree on the concordance
      of these 2 clinical research methods. DESIGN: Systematic comparison of protocol
      designs, study selection, definitions of agreement, analysis methods, and
      reported discrepancies between large trials and meta-analyses. RESULTS: More
      discrepancies were claimed when large trials were selected from influential
      journals (which may prefer trials disagreeing with prior evidence) than from
      already performed meta-analyses (which may target homogeneous trials) and when
      both primary and secondary (rather than only primary) end points were considered.
      Depending on how agreement was defined, kappa coefficients varied from 0.22 (low
      agreement) to 0.72 (excellent agreement). The correlation of treatment effects
      between large trials and meta-analyses varied from -0.12 to 0.76, but was more
      similar (0.50-0.76) when only primary end points were considered. When both the
      magnitude and uncertainty of treatment effects were considered, large trials
      disagreed with meta-analyses 10% to 23% of the time. Discrepancies were
      attributed to different disease risks, variable protocols, quality, and
      publication bias. CONCLUSIONS: Comparisons of large trials with meta-analyses may
      reach different conclusions depending on how trials and meta-analyses are
      selected and how end points and agreement are defined. Scrutiny of these 2 major
      research methods can enhance our appreciation of both for guiding medical
      practice.

PMID- 9546569
TI  - Does this patient have deep vein thrombosis?
AB  - OBJECTIVE: To review the validity of the clinical assessment and diagnostic tests
      in patients with suspected deep vein thrombosis (DVT). METHODS: A comprehensive
      review of the literature was conducted by searching MEDLINE from 1966 to April
      1997. RESULTS: Individual symptoms and signs alone do not reliably predict which
      patients have DVT. Overall, the diagnostic properties of the clinical examination
      are poor; the sensitivity of the clinical examination ranges from 60% to 96%, and
      the specificity ranges from 20% to 72%. However, using specific combinations of
      risk factors, symptoms, and physical signs for DVT, clinicians can reliably
      stratify patients with suspected DVT into low, moderate, or high pretest
      probability categories of actually suffering from DVT. This stratification
      process in combination with noninvasive testing, such as compression
      ultrasonography, simplifies the management strategies for patients with suspected
      DVT. CONCLUSIONS: Use of a clinical prediction guide that includes specific
      factors from both the history and physical examination in combination with
      noninvasive tests simplifies management strategies for patients with suspected
      DVT.

PMID- 9546570
TI  - Diagnosis and treatment of attention-deficit/hyperactivity disorder in children
      and adolescents. Council on Scientific Affairs, American Medical Association.
AB  - OBJECTIVE: To deal with public and professional concern regarding possible
      overprescription of attention-deficit/hyperactivity disorder (ADHD) medications,
      particularly methylphenidate, by reviewing issues related to the diagnosis,
      optimal treatment, and actual care of ADHD patients and of evidence of patient
      misuse of ADHD medications. DATA SOURCES: Literature review using a National
      Library of Medicine database search for 1975 through March 1997 on the terms
      attention deficit disorder with hyperactivity, methylphenidate, stimulants, and
      stimulant abuse and dependence. Relevant documents from the Drug Enforcement
      Administration were also reviewed. STUDY SELECTION: All English-language studies
      dealing with children of elementary school through high school age were included.
      DATA EXTRACTION: All searched articles were selected and were made available to
      coauthors for review. Additional articles known to coauthors were added to the
      initial list, and a consensus was developed among the coauthors regarding the
      articles most pertinent to the issues requested in the resolution calling for
      this report. Relevant information from these articles was included in the report.
      DATA SYNTHESIS: Diagnostic criteria for ADHD are based on extensive empirical
      research and, if applied appropriately, lead to the diagnosis of a syndrome with
      high interrater reliability, good face validity, and high predictability of
      course and medication responsiveness. The criteria of what constitutes ADHD in
      children have broadened, and there is a growing appreciation of the persistence
      of ADHD into adolescence and adulthood. As a result, more children (especially
      girls), adolescents, and adults are being diagnosed and treated with stimulant
      medication, and children are being treated for longer periods of time.
      Epidemiologic studies using standardized diagnostic criteria suggest that 3% to
      6% of the school-aged population (elementary through high school) may suffer from
      ADHD, although the percentage of US youth being treated for ADHD is at most at
      the lower end of this prevalence range. Pharmacotherapy, particularly use of
      stimulants, has been extensively studied and generally provides significant short
      term symptomatic and academic improvement. There is little evidence that
      stimulant abuse or diversion is currently a major problem, particularly among
      those with ADHD, although recent trends suggest that this could increase with the
      expanding production and use of stimulants. CONCLUSIONS: Although some children
      are being diagnosed as having ADHD with insufficient evaluation and in some cases
      stimulant medication is prescribed when treatment alternatives exist, there is
      little evidence of widespread overdiagnosis or misdiagnosis of ADHD or of
      widespread overprescription of methylphenidate by physicians.

PMID- 9546572
TI  - Preempting the memory of pain.

PMID- 9546571
TI  - HIV infection and AIDS in the public health and health care systems: the role of
      law and litigation.
AB  - The AIDS Litigation Project has reviewed nearly 600 reported cases involving
      individuals with human immunodeficiency virus (HIV) infection and acquired
      immunodeficiency syndrome (AIDS) in the federal and state courts in the United
      States between 1991 and 1997. Cases were identified through a federal and 50
      state computer and library search. An important subset of litigation relates to
      HIV/AIDS in the public health and health care systems, since the law affects
      health care institutions and professionals, patients, and public health policy in
      America. This subset of HIV/AIDS litigation includes testing and reporting;
      privacy, the duty to warn, and the right to know; physician standards of care in
      prevention and treatment; and discrimination and access to health care. In broad
      terms, the review demonstrates a reliance on voluntary testing and protection of
      patient privacy through HIV-specific statutes and the common law. Negligence with
      potential civil and criminal liability has been alleged in cases of erroneous or
      missed diagnosis of HIV infection. In the first AIDS case to be considered by the
      Supreme Court, the Court will decide whether patients with asymptomatic HIV
      infection are protected under the Americans With Disabilities Act. Considerable
      progress has been made, both socially and legally, during the first 2 decades of
      the epidemic, but much still needs to be accomplished to protect privacy, prevent
      discrimination, and promote tolerance.

PMID- 9546573
TI  - Profiles in primary care.

PMID- 9546574
TI  - Eugene McGregor, MD: a legacy of general practice.

PMID- 9546575
TI  - Protective effect of an SDF-1 variant in HIV disease: abstract and commentary.

PMID- 9546576
TI  - Hormone response units: one plus one equals more than two.
AB  - The transcription rate of many genes, and particularly those which code for
      metabolically important proteins, is regulated by various hormones. Detailed
      analysis of the promoters of these genes has shown that, while functional
      'Hormone response elements' exist, the hormonal responsiveness of many promoters
      is often synergistically mediated by several cis-elements, collectively referred
      to as a hormone response unit. The utilization of a hormone response unit to
      mediate a response offers several regulatory advantages, including an expansion
      of the range of transcriptional responses and modulation of the response by
      tissue- and developmental-specific cues. Furthermore, the presence of Hormone
      Response Units may provide a mechanism for the coordination of information from
      two or more signaling pathways into a single, integrated and exquisitely
      controlled transcriptional response. The protein-protein interactions that likely
      mediate many of the synergistic functional characteristics of Hormone Response
      Units may provide unique targets for therapeutic intervention.

PMID- 9546578
TI  - Comparison of biochemical effects produced by calcium ions and by monomers of
      polyacrylamide (acrylamide and bisacrylamide) on strains of Saccharomyces
      cerevisiae used for production of chiral synthons.
AB  - The biochemical behaviour of four commercial strains of Saccharomyces cerevisiae
      was studied in the presence of calcium ions, acrylamide and bisacrylamide.
      Calcium ions at a concentration of 300 microM induced an increase of NAD(P)+
      reduction in commercial Turkish and American strains, while in Chilean and
      Brazilian commercial strains, it diminished NAD(P)+ reduction. On the other hand,
      polyacrylamide monomers (acrylamide and bisacrylamide) induced a decrease of
      NAD(P)+ reduction in all strains studied in this paper. When membrane potential
      (delta psi) and oxygen consumption were measured in the presence of
      polyacrylamide monomers, a decrease of both was observed in all strains studied.

PMID- 9546579
TI  - Diazepam induced early oxidative changes at the subcellular level in rat brain.
AB  - Studies were conducted to ascertain any involvement of free radical mediated
      prooxidative processes in different brain regions following diazepam
      administration. A significant decrease in TBA reactive substance formation was
      observed in cerebral cortex, cerebellum and brain stem regions after single doses
      of 1.5, 3 and 6 mg/kg b.wt. For further studies rats were given diazepam (i.p.)
      at 3 mg/kg body weight dose and sacrificed after 1 h to follow changes in the
      pro/antioxidant status. An enhancement in the TBARS formation was found in the
      mitochondrial fractions from cerebral cortex and brain stem. This effect was
      highest in brain stem being 107% as compared to controls. In the post
      mitochondrial fraction, cerebellum showed 49% enhancement whereas decreased
      formation of thiobarbituric acid reactive substances was observed in cerebral
      cortex and brain stem. Isozymes of superoxide dismutase showed a decrease in
      activity which was region dependent. Even though, total thiols were not
      significantly altered, free thiols showed depletion in cerebellum (39.8%) and
      brain stem (50%). Glutathione reductase activity was also decreased in cerebellum
      and brain stem. The results indicate that a single dose of diazepam causes free
      radical mediated changes and the modulatory response of antioxidant defences
      appears to be region specific.

PMID- 9546580
TI  - G-CSF receptor-mediated up-regulation of c-fos but not c-raf mRNA expression in
      myeloid cells.
AB  - Granulocyte colony stimulating factor (G-CSF) regulates survival, proliferation,
      and differentiation of myeloid precursor cells. One of the signaling mechanisms
      for the G-CSF receptor (G-CSF-R) involves the activation of Ras/MAP kinase (MEK)
      pathway. Since Raf is an important, common link between Ras and MEK in the Ras
      Raf-MEK cascade, we studied the expression of c-raf mRNA in G-CSF-treated myeloid
      precursor cell lines--NFS-60 and HL-60. G-CSF did not alter c-raf mRNA expression
      in these cells up to 24 h, but induced a transient up-regulation of c-fos mRNA
      expression between 15-60 min post-treatment. Our results show that G-CSF triggers
      a de novo induction of c-fos but not c-raf mRNA, and suggests that G-CSF-R
      mediated activation of Ras/MEK pathway may involve post-transcriptional
      mechanisms of Raf regulation.

PMID- 9546581
TI  - Increased mRNA expression of cardiac renin-angiotensin system and collagen
      synthesis in spontaneously hypertensive rats.
AB  - Hypertensive cardiac hypertrophy is associated with the accumulation of collagen
      in the myocardial interstitium. Previous studies have demonstrated that this
      myocardial fibrosis accounts for impaired myocardial stiffness and ventricular
      dysfunction. Although cardiac fibroblasts are responsible for the synthesis of
      fibrillar collagen, the factors that regulate collagen synthesis in cardiac
      fibroblasts are not fully understood. We investigated the effects of angiotensin
      II on cardiac collagen synthesis in cardiac fibroblasts. Cardiac fibroblasts of
      10 week old spontaneously hypertensive rats and age-matched Wistar-Kyoto rats
      were prepared and maintained in culture medium supplemented with 10% fetal calf
      serum. The expression of mRNA of the renin-angiotensin system (renin,
      angiotensinogen, angiotensin converting enzyme) was determined by using a
      ribonuclease protection assay. Basal collagen synthesis in cardiac fibroblasts
      from spontaneously hypertensive rats was 1.6 fold greater than that in the cell
      of Wistar-Kyoto rats. Angiotensin II stimulated collagen synthesis in cardiac
      fibroblasts in a dose-dependent manner. The responsiveness of collagen production
      to angiotensin II was significantly enhanced in cardiac fibroblasts from
      spontaneously hypertensive rats (100 nM angiotensin II resulted in 185 +/- 18%
      increase above basal levels, 185 +/- 18 versus 128 +/- 19% in Wistar-Kyoto rats p
      < 0.01). This effect was receptor-specific, because it was blocked by the
      competitive inhibitor saralasin and MK 954. These results indicate that collagen
      production was enhanced in cardiac fibroblasts from spontaneously hypertensive
      rats, that angiotensin II had a stimulatory effect on collagen synthesis in
      cardiac fibroblasts, and that cardiac fibroblasts from spontaneously hypertensive
      rats were hyper-responsive to stimulation by angiotensin II. Level of angiotensin
      and renin mRNA expressed in ventricles, and angiotensinogen mRNA expressed in
      fibroblasts from SHR were higher than those from WKY. These findings suggest that
      the cardiac renin-angiotensin system may play an important role in collagen
      accumulation in hypertensive cardiac hypertrophy.

PMID- 9546583
TI  - Muscle metabolism and quality (MQI) in prediabetic sedentary man.
AB  - Twelve pairs of healthy sedentary males matched for their body mass index (BMI)
      with either a low insulin response (LIR; a stage of prediabetes) or a high (HIR;
      controls) to a standardized glucose infusion test (GIT) were studied in respect
      to their exercise capacities (W(OBLA), W(SL) and relative W(OBLA):W(OBLA) x
      W(SL)(-10 x 100), muscle fiber composition (%ST), muscle citrate synthase
      activity (CS), muscle ubiquinone (MUQ), MUQ over %ST (muscle quality index, MQI),
      and peripheral insulin sensitivity (PIS) as described with insulin-clamp
      techniques (SIGITmean). LIR and HIR displayed normal PIS and positive
      relationships versus exercise capacity. LIR's but not HIR's relative W(OBLA) was
      related to CS as earlier only documented in endurance athletes but at a lower
      level than in athletes. This pointed at a poor peripheral oxygen delivery in LIR.
      LIR's MQI decreased relative to HIR's the higher the muscle CS indicating radical
      related muscle trauma in LIR as in athletes. LIR representing prediabetes
      described muscle anomalies, which could represent prestages of the lesions
      observed in type-2 diabetes. They are claimed to be responsible for insulin-,
      glucose-, lipid-resistance, and peripheral circulatory resistance.

PMID- 9546582
TI  - Identification and activation of mitogen-activated protein (MAP) kinase in normal
      human osteoblastic and bone marrow stromal cells: attenuation of MAP kinase
      activation by cAMP, parathyroid hormone and forskolin.
AB  - The mitogen-activated protein (MAP) kinases (p44mapk and p42mapk), also known as
      extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), are activated in
      response to a variety of extracellular signals, including growth factors,
      hormones and, neurotransmitters. We have investigated MAP kinase signal
      transduction pathways in normal human osteoblastic cells. Normal human bone
      marrow stromal (HBMS), osteoblastic (HOB), and human (TE85, MG-63, SaOS-2), rat
      (ROS 17/2.8, UMR-106) and mouse (MC3T3-E1) osteoblastic cell lines contained
      immunodetectable p44mapk/ERK1 and p42mapk/ERK2. MAP kinase activity was measured
      by 'in-gel' assay using myelin basic protein as the substrate. Mainly ERK2 was
      rapidly activated (within 10 min) by bFGF, IGF-I and PDGF-BB in normal HOB, HBMS
      and human osteosarcoma cells, whereas both ERK1 and ERK2 were activated by growth
      factors in rat osteoblast-like cell lines, ROS 17/2.8 and UMR-106. The ERK1
      activation was greater than the ERK2 in ROS 17/2.8 cells. Furthermore, ERK2 was
      also activated by bFGF and PDGF-BB in the mouse osteoblastic cell line, MC3T3-E1.
      This is the first demonstration of inter-species differences in the activation of
      MAP kinases in osteoblastic cells. Cyclic AMP derivatives or cAMP generating
      agents such as PTH and forskolin inhibited ERK2 activation by bFGF and PDGF-BB
      suggesting a 'cross-talk' between the two different signalling pathways activated
      by receptor tyrosine kinases and cAMP-dependent protein kinase. The accumulated
      results also suggest that the MAP kinases may be involved in mediating mitogenic
      and other biological actions of bFGF, IGF-I and PDGF-BB in normal human
      osteoblastic and bone marrow stromal cells.

PMID- 9546584
TI  - Effects of peroxide on the fluorescence of the Ca2+ probe Fluo 3 and the pH probe
      BCECF.
AB  - Fluorescence probes are invaluable tools in monitoring intracellular ion
      concentrations. They have also been used for studying how reactive oxygen species
      alter these concentrations and yet there are no studies indicating how reactive
      oxygen species directly affect the characteristics of the probes. Our concern was
      that if reactive oxygen were to affect characteristics of these probes, these
      measurements would be inconsequential. Therefore, we examined the effects of
      peroxide on the Ca2+-sensitive dye Fluo 3 and the pH sensitive dye BCECF.
      Peroxide concentrations below 10 mM did not alter fluorescence or binding
      characteristics of either dye. Since the concentrations of peroxide used in most
      pathophysiological experiments are in the micromolar range, we conclude that
      these probes are appropriate for monitoring the effects of peroxide on
      intracellular ion concentrations.

PMID- 9546585
TI  - Reduced 40S initiation complex formation in skeletal muscle during sepsis.
AB  - Severe muscle wasting is a characteristic feature of sepsis. We have previously
      established that the rate of protein synthesis in muscles composed of fast-twitch
      fibers is severely diminished in response to sepsis. The present studies
      investigate the biochemical reactions responsible for the decreased rate of
      protein synthesis using gastrocnemius from control and septic rats perfused in
      situ. Analysis of free ribosomal subunits indicated peptide-chain initiation was
      impaired by infection. To characterize biochemical reactions in the pathway of
      peptide-chain initiation affected, the effect of sepsis on the incorporation of
      initiator [35S]methionyl-tRNA (met-tRNA(imet)) into the 40S initiation complex
      was examined. Sepsis caused a 65% decrease in the binding of radiolabelled met
      tRNA(imet) to the 40S initiation complex compared with controls. The binding of
      met-tRNA(met) to the 40S ribosome is regulated by eukaryotic initiation factor
      eIF-2B, whose activity can be modulated in part by the redox state of pyridine
      dinucleotides. The mean cytoplasmic NADH/NAD+ ratio was increased 2 fold in
      sepsis, while the NADPH/NADP+ ratio was unchanged. These findings identify the
      formation of the 40S initiation complex as a defect in the protein synthesis
      machinery during sepsis. The decreased formation of the 40S initiation complex in
      muscle could not be explained by changes in the cytoplasmic redox state.

PMID- 9546586
TI  - Heterogeneous cellular expression of creatine kinase isoenzyme during normal rat
      heart development.
AB  - The degree to which developmentally related alterations in cardiac creatine
      kinase (CK) activity reflect modification of CK isoenzyme gene expression remains
      uncertain. The present studies addressed this question by assessing multiple
      aspects of CK in rat heart during the perinatal to adult transition. In addition
      to whole tissue, isolated and purified muscle and nonmuscle cells were studied,
      as well as myofibrillar, mitochondrial, and cytosolic subcellular fractions.
      Whole homogenate CK enzyme specific activity nearly doubled during the weanling
      to adult developmental period. Muscle cell CK activity increased by a similar
      magnitude. Nonmuscle cell activity decreased. In the adult heart, both
      myofibrillar and mitochondrial CK activities were augmented versus the weanling
      heart. The cytoplasmic fraction activity held constant during development.
      Electrophoretic isoenzyme analyses of both weanling and adult cardiac muscle
      cells indicated the presence of mitochondrial CK and MM-CK isoforms. Weanling
      heart nonmuscle cells contained mitochondrial, MM, MB, and BB isoforms; however,
      BB isoform was not detected in the adult heart nonmuscle cells. Arrhenius plots
      provided information regarding heart muscle and nonmuscle cell alterations during
      development. CK activation energies were also determined for whole tissue,
      muscle/nonmuscle cells, myofibrils, mitochondria, and cytosol. Results
      demonstrate that heterogeneous muscle/nonmuscle cellular composition and
      differential myofibrillar/mitochondrial subcellular composition account for
      normal, developmentally related changes in heart CK enzyme activity. CK isoenzyme
      gene expression changes were not detected in cardiac muscle cells, and transition
      of CK-B to CK-M gene expression is limited to nonmuscle cells during normal,
      weanling to adult development in the rat heart.

PMID- 9546577
TI  - Biochemical and molecular mechanisms regulating apoptosis.
AB  - In eukaryotes, the regulation of tissue cell numbers is a critical homeostatic
      objective that is achieved through tight control of apoptosis, mitosis and
      differentiation. While much is known about the genetic regulation of cell growth
      and differentiation, the molecular basis of apoptosis is less well understood.
      Genes involved in both cell proliferation and apoptosis reflect the role of some
      stimuli in both of these processes, the cell response depending on the overall
      cellular milieu. Recent research has given fascinating insights into the complex
      genetic and molecular mechanisms regulating apoptosis. A picture is emerging of
      the initiation in certain cells, after an apoptotic trigger, of sequential gene
      expression and specific signal transduction cascades that guide cells along the
      cell death pathway. Changes in gene expression precede the better known
      biochemical and morphological changes of apoptosis. It seems possible that, as a
      result of increased understanding of the cellular events preceding cell death,
      apoptosis may become more amenable to manipulation by appropriate drug- and gene
      based therapies.

PMID- 9546587
TI  - Characterization of the phosphorylation state of natriuretic peptide receptor-C.
AB  - Many internalized receptors are known to be phosphorylated within their
      cytoplasmic domain. Natriuretic peptide receptor-C (NPR-C) is a covalent
      homodimer primarily involved in the internalization of bound ligand resulting in
      tissue uptake and degradation of natriuretic peptides. In this report, we have
      investigated the phosphorylation state of NPR-C receptors present at high level
      in rat aortic smooth muscle cells (RASM). 32P labeled cells, NPR-C purification
      and phosphoamino acid analysis clearly demonstrate that NPR-C exists as a
      phosphoprotein in RASM cells and that phosphorylation occurs exclusively on
      serine residues. Transient expression of bovine NPR-C in Cos-P cells of kidney
      origin confirmed that phosphorylation occurs within the cytoplasmic domain of the
      receptor. These results provide the first evidence for NPR-C phosphorylation as
      well as a model for future studies of its role in altering receptor function.

PMID- 9546588
TI  - Potential role of NF-kB and RXR beta like proteins in interferon induced HLA
      class I and beta globin gene transcription in K562 erythroleukaemia cells.
AB  - Positive effects of biological response modifiers on cancer cells are usually
      measured using markers for increased immunogenicity as well as those for
      increased differentiation of the cells. An increase in levels of HLA class I
      antigens and the adult (beta) globin molecules are two such markers that may be
      used to assess the effect of modulators like interferons on the K562
      erythroleukaemia cell line. Although interferon mediated up regulation of gene
      expression is thought to be primarily regulated by binding of proteins to the
      Interferon responsive cis elements in the promoters of IFN responsive genes,
      recent evidence has shown the induction of other transcriptional activators in
      response to IFN treatment. We present evidence for one such instance wherein up
      regulation of HLA class I and beta globin gene transcription are accompanied by
      induction of binding activities similar to RXR beta and kB proteins in K562
      cells.

PMID- 9546589
TI  - Characterization of free and glyceride-esterified long chain fatty acids in
      different skeletal muscle types of the rat.
AB  - The plasma-borne long-chain free fatty acids (FFA) enter skeletal muscle cells.
      Upon entering they are oxidized or esterified and a fraction remains free (non
      esterified). The data on free fatty acids in skeletal muscles remain highly
      controversial. Furthermore, the composition of individual fatty acids in various
      lipid fractions including free fatty acids, monoglyceride and diglyceride in
      muscles has not been characterized. Also data on the composition of fatty acids
      esterified into muscle triglycerides and phospholipids are incomplete. The
      present study was undertaken to examine a composition of fatty acids in lipid
      fractions of different skeletal muscle types. For this purpose, samples of the
      rat soleus, red and white portions of gastrocnemius were excised, trimmed of
      visible fat and fascias and immediately frozen in liquid nitrogen. Samples were
      then pulverized and, lipids were extracted and fractionated by thin-layer
      chromatography. Individual long-chain fatty acids in different fractions were
      identified, characterized and quantitated by gas-liquid chromatography. FFA
      composition in the plasma was also determined. The total FFA content in the
      soleus, red and white gastrocnemius was 69.1 +/- 10.8, 49.0 +/- 13.6 and 22.7 +/-
      8.6 nmol/g, respectively. Palmitic and oleic acids were the major fatty acids in
      the muscles FFA fraction. Monoglyceride fraction of each muscle contained
      palmitic, stearic and linoleic acid as the major fatty acids, Diglyceride
      fraction contained mostly palmitic and oleic acid whereas triglyceride fraction
      mostly palmitic and linoleic acid.. The fraction of phospholipids was composed
      mostly of palmitic and linoleic acid but contained also considerable percentage
      of archidonic acid. Total plasma FFA/muscle FFA ratio depended on a muscle type
      and was: 2.4 in the soleus, 3.5 in the red and 7.4 in the white gastrocnemius.
      This assured transport of FFA to the myocytes. However, there were great
      differences in the ratio between particular FFA within the same muscle as well
      between the muscles. It indicates that individual FFA are either selectively
      transported from the plasma to the muscles or selectively used within the
      myocytes or both.

PMID- 9546590
TI  - Evidence for HSP70-like protein in the RBC membrane of the hereditarily anemic
      Belgrade laboratory (b/b) rat.
AB  - We have demonstrated that in normal and b/b rat red blood cells (RBCs) hsp70-like
      protein (heat shock protein 70-like) is localized in the cytosol and it is
      exported via exosomes during in vivo reticulocytes maturation. As we have
      presumed, in the mutant (b/b) rat, hsp70-like protein transfers from cytosol to
      the RBC membrane. In the normal rat RBCs this happens when those cells are
      submitted to heat stress conditions. Our study indicates that the presence of
      hsp70-like protein in the b/b rat RBC plasma membrane is consistent with a
      primary defect and is not a consequence of life long stress, i.e. hypoxia.

PMID- 9546592
TI  - Pharmacological characterization of an endogenous negative inotrophic factor
      (ENIF) from porcine heart.
AB  - Recently we have been successful in isolating an endogenous negative inotropic
      factor (ENIF) from porcine left ventricular tissue. In this study, we have
      characterized its pharmacological properties. The results of the study
      demonstrated that ENIF produces a concentration-dependent negative inotropic
      response on both guinea pig left atria and right ventricular trabeculae. The
      maximal reduction in contractile force produced by 300 ul of ENIF (5 ml bath) on
      atria and trabeculae were 90.0 +/- 0.8% and 77.5 +/- 6%. Atria, however, was
      significantly more sensitive to ENIF than trabeculae. The ED 50 of ENIF for atria
      was found to be 38 ul as opposed to ED 50 of 100 ul of ENIF for trabeculae.
      Acetylcholine (ACh), a muscarinic receptor agonist, decreased the contractile
      force of guinea pig atria in a dose-dependent manner with a maximal decline in
      the contractile force of 90%. However, none of the concentration of ACh used
      affected the contractile function of the trabeculae. Atropine (1 uM) completely
      blocked the negative inotropic response on atria of all the doses of ACh used.
      The same dose of atropine, however, was unable to influence the negative
      inotropic effect of any of the doses of ENIF used on either the atria or
      trabeculae preparations in our study. The maximal decline in the contractile
      force of atria was e.g. 94 and 95% in the presence and absence of atropine
      respectively. These data demonstrate that the myocardial negative inotropic
      effect of ENIF is not mediated via the cholinegic receptor mechanism.

PMID- 9546591
TI  - Protection by ebselen against cisplatin-induced nephrotoxicity: antioxidant
      system.
AB  - This study was designed to investigate the cisplatin-induced alteration in renal
      antioxidant system and the nephroprotection with ebselen. Male Wistar rats were
      injected with (1) vehicle control; (2) cisplatin; (3) ebselen; and (4) cisplatin
      plus ebselen. Rats were sacrificed three days post-treatment and plasma as well
      as kidney were isolated and analyzed. Plasma creatinine increased 598% following
      cisplatin administration alone which decreased by 158% with ebselen pretreatment.
      Cisplatin-treated rats showed a depletion of renal glutathione (GSH) levels (52%
      of control), while cisplatin plus ebselen injected rats had GSH values close to
      the controls. Antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GSH-Px) activities decreased 38, 75 and 62% of control,
      respectively, and malondialdehyde (MDA) levels increased 174% of control
      following cisplatin administration, which were restored to control levels after
      ebselen treatment. The renal platinum level did not significantly change with
      ebselen pretreatment. This study suggests that the protection offered by ebselen
      against cisplatin-induced nephrotoxicity is partly related to the sparing of
      antioxidant system.

PMID- 9546594
TI  - Antioxidant properties of indapamide, 5-OH indapamide and hydrochlorothiazide
      evaluated by oxygen-radical absorbing capacity and electron paramagnetic
      resonance.
AB  - The aim of these experiments was to investigate the radical scavenging properties
      of three diuretics: indapamide (IND) and its major metabolite, 5-OH indapamide (5
      OH IND), compared to a reference diuretic, hydrochlorothiazide (HTZ). Electron
      Paramagnetic Resonance (EPR) was used to determine the scavenging abilities of
      these compounds on enzymatically produced superoxide radical anion, with 5,5
      dimethyl-1-pyrroline N-oxide (DMPO) used as a spin-trap. These experiments
      revealed that IND and specially 5-OH IND were effective superoxide radical anion
      scavengers at 0.2 mg/ml. In the second part of these studies, allophycocyanin was
      used as an indicator of free radical mediated protein damage. In the assay, 2,2'
      azobis(2-amidinopropane) hydrochloride (AAPH) was used as a peroxyl radical
      generator, Trolox (a water-soluble analogue of vitamin E) as a control standard,
      and the loss of allophycocyanin fluorescence was monitored. The antioxidant
      effects of the diuretics were expressed in oxygen-radical absorbing capacity
      (ORAC), where one ORAC unit equals the net protection produced by 1 microM
      Trolox. HTZ showed no protection up to 100 microM final concentration, whereas
      IND and 5-OH IND showed linear correlation with respect to concentration when
      expressed in ORAC units: 5-OH IND induced the highest protection against peroxyl
      radical. The above observations suggested that IND and 5-OH IND are potent
      radical scavengers, with the metabolite 5-OH IND having a superior antioxidant
      potency than IND. By contrast, HTZ had no effect. These radical scavenging
      properties of 5-OH IND may be of clinical interest for vascular protection and
      may help to protect the heart from oxidative injury.

PMID- 9546593
TI  - Chemical hypoxia triggers apoptosis of cultured neonatal rat cardiac myocytes:
      modulation by calcium-regulated proteases and protein kinases.
AB  - Myocardial infarctions and stroke arise primarily as a result of hypoxia/ischemia
      induced cell injury. However, the molecular mechanism of cardiac cell death due
      to hypoxia has not been elucidated. We showed here that chemical hypoxia induced
      by 1 mM azide triggered apoptosis of isolated neonatal rat ventricular cardiac
      myocytes but had no effect on cardiac fibroblasts. The azide-induced
      cardiomyocyte apoptosis could be characterized by a reversible initiation phase
      (0-46 h after azide exposure) during which cytosolic ATP levels remained little
      affected. This was followed by an irreversible execution phase (12-18 h)
      exhibiting prominent internucleosomal DNA fragmentation, cell membrane leakage,
      mitochondrial dysfunction, and increased calpain messenger RNA. Blocking
      extracellular calcium influx or intracellular calcium release was each effective
      in suppressing myocyte apoptosis. Cell death was also found to be mediated by
      calcium sensitive signal transduction events based on the use of specific
      antagonists. Consistent with the induction of calpain expression during
      apoptosis, blocking de novo protein synthesis and calpain activity inhibited cell
      death. These regulatory features coupled with the ease of the cell system suggest
      that the myocyte apoptosis model described here should be useful in the study of
      events leading to the demise of the myocardium.

PMID- 9546595
TI  - Protein tyrosine phosphatase gene expression analysis in Swiss 3T3 fibroblasts.
AB  - The aim of this study was to identify protein tyrosine phosphatases (PTPs)
      expressed in Swiss 3T3 fibroblasts and to examine their expression levels as well
      as to characterize quantitative aspects of RT-PCR based on degenerate
      deoxyoligonucleotides. By using an RT-PCR assay based on degenerate
      deoxyoligonucleotide primers, expression of mRNAs for two cytoplasmic- and six
      transmembrane-type PTPs in Swiss 3T3 cells was detected. The sequences of two of
      them are new. Among nine analyzed PTPs expressed to widely varied extends, only
      three have mRNA levels high enough to be seen on Northern blots with 10 microg of
      total RNA per lane. The frequencies with which the examined PTPs are represented
      among the PCR amplification products, correlate stronger with the primer
      fidelity, defined as the number of mismatches between the primer- and the cDNA
      target-sequences, rather than with the PTP expression levels. In conclusion, an
      RT-PCR assay based on degenerate primers can be successfully used to sample the
      expressed PTPs and to identify new members of this gene family. However, reliable
      quantification of their mRNA levels can only be achieved using the classical
      approaches, like Northern, RNase protection assay or nondegenerate quantitative
      RT-PCR.

PMID- 9546596
TI  - Purification and characterization of the rat liver gamma-butyrobetaine
      hydroxylase.
AB  - The biosynthesis of carnitine from lysine and methionine involves five enzymatic
      reactions. Gamma-butyrobetaine hydroxylase (BBH; EC 1.14.11.1) is the last enzyme
      of this pathway. It catalyzes the reaction of hydroxylation of gamma
      butyrobetaine to carnitine. This enzyme had never been purified to homogeneity
      from rat tissue. This paper describes the purification and characterization of
      the rat liver BBH. This protein has been purified some 413 fold by ion exchange,
      affinity and gel-filtration chromatographies and appears as a dimere of 43,000
      Daltons subunits by PAGE. The affinity chromatography column used in the
      purification process utilizes 3-(2,2,2-trimethylhydrazinium)propionate (THP), a
      BBH inhibitor, as the ligand. Polyclonal antibodies were raised against the liver
      enzyme. They were able to precipitate BBH activity in either a crude liver
      extract or a purified fraction of the enzyme. Furthermore, it crossreacts with a
      43 kDa protein in the liver. No evidence for extra hepatic enzyme was found.

PMID- 9546597
TI  - Shigella dysenteriae type 1 toxin induced lipid peroxidation in enterocytes
      isolated from rabbit ileum.
AB  - To evaluate the role of reactive oxygen species (ROS) in Shigella dysenteriae 1
      toxin (STx) mediated intestinal infection, the ligated rabbit small intestinal
      loops were injected with STx. The enterocytes isolated from STx treated rabbit
      ileal loops had a significantly higher level of lipid peroxidation as compared to
      enterocytes isolated from control rabbit ileum. To study the role of second
      messengers in STx mediated intestinal damage, the in vivo and in vitro effects of
      modulators of lipid peroxidation of enterocytes were used. The presence of Ca2+
      ionophore A23187 enhanced the extent of lipid peroxidation in enterocytes
      isolated from the control and STx treated rabbit ileum. However, 1-verapamil only
      marginally decreased the lipid peroxidation level of enterocytes isolated from
      STx treated rabbit ileum. The in vitro effect of modulators was in agreement with
      in vivo studies. Dantrolene significantly decreased the extent of lipid
      peroxidation of enterocytes isolated from STx treated rabbit ileum. PMA
      significantly increased the lipid peroxidation level of enterocytes isolated from
      control ileum. However, PMA could not further enhance the lipid peroxidation
      level of enterocytes isolated from STx treated rabbit ileum. The presence of H-7
      significantly decreased the extent of lipid peroxidation of enterocytes isolated
      from STx treated rabbit ileum. In vitro effect of PMA and H-7 was in agreement
      with that of in vivo findings. The role of arachidonic acid metabolites,
      prostaglandins (PGs), in mediating STx induced lipid peroxidation was also
      studied. The presence of indomethacin (a PG synthesis inhibitor) significantly
      decreased the lipid peroxidation induced by STx. These findings suggest that
      lipid peroxidation induced by STx is mediated through cytosolic calcium. The
      increase in (Ca2+)i leads to activation of PKC. A significant decrease in the
      enterocyte levels of antioxidant enzymes superoxide dismutase, catalase and
      reduced glutathione in STx treated rabbit ileum as compared to control was seen.
      A significant decrease in vitamin E levels was also observed. This suggests that
      there is decreased endogenous intestinal protection against ROS in STx mediated
      intestinal infection which could contribute to enterocyte membrane damage that
      ultimately leads to changes in membrane permeability and thus to fluid secretion.

PMID- 9546598
TI  - Lipoperoxidation of rod outer segments of bovine retina is inhibited by soluble
      binding proteins for fatty acids.
AB  - In the present study it was investigated if soluble-binding proteins for fatty
      acids (FABPs) present in neural retina show protection from in vitro
      lipoperoxidation of rod outer segment membranes (ROS). After incubation of ROS in
      an ascorbate-Fe++ system, at 37 degrees C during 90-120 min, the total cpm
      originated from light emission (chemiluminescence) was found to be lower in those
      membranes incubated in the presence of soluble binding proteins for fatty acids.
      The fatty acid composition of rod outer segment membranes was substantially
      modified when subjected to non-enzymatic lipoperoxidation with a considerable
      decrease of docosahexaenoic acid (22:6 n-3) and arachidonic acid (20:4 n-6). As a
      result of this, the unsaturation index, a parameter based on the maximal rate of
      oxidation of specific fatty acids was higher in the native and control membranes
      when compared with peroxidized ones. A similar decrease of chemiluminescence was
      observed with the addition of increasing concentrations of native or delipidated
      FABP retinal containing fractions to rod outer segment membranes. These results
      indicate that soluble proteins with fatty acid binding properties may act as
      antioxidant protecting rod outer segment membranes from deleterious effect.

PMID- 9546599
TI  - Histone H1 isoforms purified from rat liver bind nonspecifically to the nuclear
      factor 1 recognition sequence and serve as generalized transcriptional
      repressors.
AB  - Two polypeptides with molecular masses of 34 and 30 kDa were copurified from rat
      liver during DNA affinity purification of a sequence-specific transcription
      factor binding to the footprint II sequence within the P2 promoter of the rat
      alpha1B adrenergic receptor (alpha1B AR) gene, and were identified by
      microsequencing their endoproteinase Lys-C-derived peptides as histone H1d and
      histone H1c, respectively. Histone H1 was previously reported to bind to the
      nuclear factor 1 (NF1) recognition sequence, although the specificity of this
      binding has been controversial. Here, DNA mobility shift and supershift assays,
      DNase I footprinting and mutational analyses indicated that the binding of
      histone H1 to the NF1 sites located within footprint II of the alpha1B AR gene P2
      promoter is nonspecific. Transient cotransfections into Hep3B cells of histone
      H1d cDNA with CAT constructs containing promoter regions of different genes
      resulted in generalized and non-specific suppression of CAT activity. The histone
      H1d-mediated repression of the activities of the alpha1B AR gene P2/CAT or beta2
      AR gene P(-186/1307)/CAT constructs was reversed by the cotransfection of a cDNA
      encoding the sequence-specific transcription factor NF1/X, and the fold increase
      in CAT activities was similar to that obtained in the absence of histone H1d.
      These results suggest that sequence-specific transcription factors counteract the
      histone H1-mediated transcriptional repression in vivo by a true activation,
      which is different from the in vitro antirepression in histone H1-repressed
      chromatin templates (Laybourn and Kadonaga, (1991) Science 254: 238-245).

PMID- 9546600
TI  - Study on lipid peroxidation potential in different tissues induced by ascorbate
      Fe2+: possible factors involved in their differential susceptibility.
AB  - Susceptibility of four major rat tissues to oxidative damage in terms of lipid
      peroxidation induced by in vitro by ascorbate-Fe2+ in homogenates and
      mitochondria has been examined. Lipid peroxidation, as assessed by thiobarbituric
      acid reactive substances (TBARS) and conjugated dienes was maximum in brain
      followed by liver, kidney and heart. However, the time course of lipid
      peroxidation showed different patterns in tissues examined. The higher
      susceptibilities of brain and liver can be explained by substrate availability
      and to a lesser extent the level of antioxidants. The differences observed in the
      tissues studied may reflect their susceptibility to degenerative diseases and
      xenobiotic toxicity which are considered as a result of oxidative damage to
      membranes.

PMID- 9546602
TI  - Steady state changes in mitochondrial electrical potential and proton gradient in
      perfused liver from rats fed a high fat diet.
AB  - In this work the protonmotive force (delta p), as well as the subcellular
      distribution of malate, ATP, and ADP were determined in perfused liver from rats
      fed a low fat or high fat diet, using density gradient fractionation in non
      aqueous solvents. Rats fed a high fat diet, despite an enhanced hepatic oxygen
      consumption, exhibit similar delta p to that found in rats fed a low fat diet,
      but when we consider the two components of delta p, we find a significant
      decrease in mitochondrial/cytosolic pH difference (delta pH(m)) and a significant
      increase in mitochondrial membrane potential (delta psi(m)) in rats fed a high
      fat diet compared to rats fed a low fat diet, which tend to compensate each
      other. In rats fed a high fat diet the concentration ratio of malate and ATP/ADP
      does not reflect the changes in delta pH(m) and delta psi(m), which represent the
      respective driving force for their transport. The findings are in line with an
      increase in substrate supply to the respiratory chain which is, however,
      accompanied by a higher energy turnover in livers from HFD rats. By this way the
      liver could contribute to the lack of weight gain from the high caloric intake in
      HFD rats.

PMID- 9546601
TI  - Inhibition of human topoisomerase II by anti-neoplastic benzazolo[3,2
      alpha]quinolinium chlorides.
AB  - Previously we reported [20] that there is no correlation between the cytotoxic
      activity of four new structural analogs of the antitumor DNA intercalator 3
      nitrobenzothiazolo[3,2-a]quinolinium chloride (NBQ-2) and their interaction with
      DNA. In the present study, we present evidence suggesting that the molecular
      basis for the anti-proliferative activity of these drugs is the inhibition of
      topoisomerase II. The NBQ-2 derivatives inhibited the relaxation of supercoiled
      DNA plasmid pRYG mediated by purified human topoisomerase II. Inhibition of the
      decatenation of kinetoplast DNA mediated by partially purified topoisomerase II
      extracted from the human histiocytic lymphoma U937 (a cell line previously shown
      to be sensitive to the drugs) was also caused by these drugs. The potency of the
      benzazolo[3,2-a]quinolinium drugs against topoisomerase II in vitro was the
      following: 7-(1-propenyl)-3-nitrobenzimidazolo[3,2-a]quinolinium chloride (NBQ
      59) > 4-chlorobenzothiazolo[3,2-a]quinolinium chloride (NBQ-76) > 7-ethyl-3
      nitrobenzimidazolo[3,2-a]quinolinium chloride (NBQ-48) > 7-benzyl-3
      nitrobenzimidazolol[3,2-a]quinolinium chloride (NBQ-38). This rank of potency for
      topoisomerase II inhibition correlated very well with the cytotoxicity elicited
      by these drugs. Furthermore, significant levels of topoisomerase II/DNA cleavage
      complex induced by these drugs in vivo were detected when U937 cells were treated
      with NBQ-59 and NBQ-76 whereas NBQ-38 and NBQ-48 produced negligible amounts of
      the cleavage complex. Our results strongly suggest that topoisomerase II is the
      major cellular target of this family of compounds.

PMID- 9546603
TI  - Use of competitive dead-end inhibitors to determine the chemical mechanism of
      action of yeast alcohol dehydrogenase.
AB  - In this work, we have postulated a comprehensive and unified chemical mechanism
      of action for yeast alcohol dehydrogenase (EC 1.1.1.1, constitutive,
      cytoplasmic), isolated from Saccharomyces cerevisiae. The chemical mechanism of
      yeast enzyme is based on the integrity of the proton relay system: His
      51....NAD+....Thr-48....R.CH2OH(H2O)....Zn++, stretching from His-51 on the
      surface of enzyme to the active site zinc atom in the substrate-binding site of
      enzyme. Further, it is based on extensive studies of steady-state kinetic
      properties of enzyme which were published recently. In this study, we have
      reported the pH-dependence of dissociation constants for several competitive dead
      end inhibitors of yeast enzyme froin their binary complexes with enzyme, or their
      ternary complexes with enzyme and NAD+ or NADH; inhibitors include: pyrazole,
      acetamide, sodium azide, 2-fluoroethanol, and 2,2,2-trifluorethanol. The unified
      mechanism describes the structures of four dissociation forms of apoenzyme, two
      forms of the binary complex E.NAD+, three forms of the ternary complex
      E.NAD+.alcohol, two forms of the ternary complex E.NADH.aldehyde and three binary
      complexes E.NADH. Appropriate pKa values have been ascribed to protonation forms
      of most of the above mentioned complexes of yeast enzyme with coenzymes and
      substrates.

PMID- 9546604
TI  - Differential expression and localization of annexin V in cardiac myocytes during
      growth and hypertrophy.
AB  - Recently it was shown that annexin V is the most prominent member of the annexin
      family in the adult heart [1]. Amongst others, annexin V has been suggested to
      play a role in developmental processes. The aim of the present study was to
      explore whether in the heart annexin V content and localization change during
      maturational and hypertrophic growth, in order to obtain indications that annexin
      V is involved in cardiac growth processes. First, in the intact rat heart annexin
      V content and localization were studied during perinatal development. It was
      clearly demonstrated that annexin V content in total heart transiently increased
      in the first week after birth, from 0.79 +/- 0.06 microg/mg protein at 1 day
      before birth to a peak value of 1.24 +/- 0.08 microg/mg protein 6 days after
      birth, whereafter annexin V protein levels declined to a value of 0.70 +/- 0.06
      microg/mg protein at 84 days after birth (p < 0.05). Differences in annexin V
      content were also observed between myocytes isolated from neonatal and adult
      hearts [0.81 +/- 0.09 and 0.17 +/- 0.08 microg/mg protein, respectively (p <
      0.05)]. Moreover, during cardiac maturational growth the subcellular localization
      of annexin V might change from a cytoplasmic to a more prominent sarcolemmal
      localization. Second, in vivo hypertrophy induced by aortic coarctation resulted
      in a marked degree of hypertrophy (22% increase in ventricular weight), but was
      not associated with a change in annexin V localization or content. The
      quantitative results obtained with intact hypertrophic rat hearts are supported
      by findings in neonatal ventricular myocytes, in which hypertrophy was induced by
      phenylephrine (10(-5) M). In the latter model no changes in annexin V content
      could be observed either. In conclusion, the marked alterations in annexin V
      content during the maturational growth in the heart suggest a possible
      involvement of this protein in this process. In contrast, the absence of changes
      in annexin V content and localization in hypertrophied hearts compared to age
      matched control hearts suggests that annexin V does not play a crucial role in
      the maintenance of the hypertrophic phenotype of the cardiac muscle cell. This
      notion is supported by observations in phenylephrine-induced hypertrophied
      neonatal cardiomyocytes.

PMID- 9546605
TI  - Protective effects of nicaraven, a new hydroxyl radical scavenger, on the
      endothelial dysfunction after exposure of pig coronary artery to hydroxyl
      radicals.
AB  - Recently, we have reported that a new synthetic compound, 1,2bis(nicotinamido)
      propane (nicaraven), improved cardiac function following preservation and
      reperfusion. In this study, we investigated the efficacy of nicaraven as a
      radical scavenger by using an in vitro model of oxidative stress, to clarify
      mechanisms of the protective effect of this new compound on reperfusion injury in
      rat heart. Ring segments of epicardial right coronary arteries (RCA) of pig were
      suspended in organ chambers and exposed to hydroxyl radicals (.OH), generated (by
      two different systems) by 0.28 mM FeSO4/0.28 mM H2O2 and DHF/Fe3+-ADP (2.4 mM, 43
      nM, and 1.56 uM, respectively) to the bathing solution for 60 min. Prior exposure
      of the coronary arteries to .OH significantly produced right-ward shift of the
      dose-response curves of the bradykinin-induced endothelium-dependent relaxations
      (an increase in the ED50 value for bradykinin by 4.37 and 1.98 times than control
      in two different .OH generating systems, respectively), but did not affect the
      maximum relaxation responses. The presence of nicaraven (10(-4) and 10(-5) M) in
      the .OH generating system, shifted the dose-response curves to bradykinin to the
      control level, suggesting a significant hydroxyl radical scavenging effect of the
      drug. These results indicate that nicaraven, a new hydroxyl radical scavenger,
      exhibits a protective effect on hydroxyl radical-induced endothelial dysfunctions
      of pig coronary artery.

PMID- 9546606
TI  - Apparent cleavage of poly(ADP-ribose) polymerase in non-apoptotic mouse LTA
      cells: an artifact of cross-reactive secondary antibody.
AB  - Proteolytic cleavage of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) to
      fragments of 89 kD and 24 kD is widely observed during apoptotic cell death. In
      the present study, labelling of a Mr approximately 89000 polypeptide was
      demonstrated in untreated mouse LTA cells during probing of immunoblots with C-2
      10 monoclonal anti-PARP antibody. The source of the labeling was traced to the
      secondary antibody preparation, which labeled a Mr approximately 89000
      polypeptide in murine LTA cells but not in human cells. These observations
      indicate that assessment of PARP cleavage must be (1) performed with appropriate
      controls when new cell lines are investigated and (2) carefully interpreted in
      light of additional biochemical or morphological data demonstrating apoptotic
      changes.

PMID- 9546607
TI  - Third calcium-modulated rod outer segment membrane guanylate cyclase transduction
      mechanism.
AB  - Ca2+-modulated rod outer segment membrane guanylate cyclase (ROS-GC1) has been
      cloned and reconstituted to show that it is regulated by two processes: one
      inhibitory, the other stimulatory. The inhibitory process is consistent with its
      linkage to phototransduction; the physiology of the stimulatory process is
      probably linked to neuronal transmission. In both regulatory processes, calcium
      modulation of the cyclase takes place through the calcium binding proteins;
      guanylate cyclase activating proteins (GCAP1 and GCAP2) in the case of the
      phototransduction process and calcium-dependent GCAP (CD-GCAP) in the case of the
      stimulatory process. The cyclase domains involved in the two processes are
      located at two different sites on the ROS-GC1 intracellular region. The GCAP1
      modulated domain resides within the aa 447-730 segment of ROS-GC1 and the CD-GCAP
      modulated domain resides within the aa 731-1054 segment. In the present study the
      GCAP2-dependent Ca2+ modulation of the cyclase activity has been reconstituted
      using recombinant forms of GCAP2 and ROS-GC1, and its mutants. The results
      indicate that consistent to phototransduction, GCAP2 at low Ca2+ concentration
      (10 nM) maximally stimulates the cyclase activity of the wild-type and its
      mutants: ext (deleted aa 8-408), kin (deleted aa 447-730) and hybrid consisting
      of the ext, transmembrane and kin domains of ANF-RGC and the C-terminal domain,
      aa 731-1054, of ROS-GC1. In all cases, it inhibits the cyclase activity with an
      IC50 of about 140 nM. A previous study has shown that under identical conditions
      the kin and the hybrid mutant are at best only minimally stimulated. Thus, the
      GCAP1 and GCAP2 signal transduction mechanisms are different, occurring through
      different modules of ROS-GC1. These findings also demonstrate that the
      intracellular region of ROS-GC1 is composed of multiple modules, each designed to
      mediate a particular calcium-specific signalling pathway.

PMID- 9546608
TI  - Binding of Shigella to rat and human intestinal mucin.
AB  - Invasion of epithelial cells by Shigella is an early step in their pathogenesis.
      Adherence is generally presumed to be a prerequisite for invasion. This study
      examined the possibility of intestinal mucins serving as initial binding sites
      for clinical isolates of S. boydii and S. sonnei. The interactions of Shigella
      with rat and human small intestinal and colonic mucin were investigated. In solid
      phase binding assays, [35S] labelled Shigella did not show any preferential
      binding to rat/human small intestinal mucin or to rat colonic mucin. On the other
      hand, Shigella bound specifically to human colonic mucin in a concentration
      dependent manner. This specific binding to human colonic mucin was not by weak
      hydrophobic interactions and could not be attributed to the presence of
      contaminating glycolipids in the mucin preparation. The human colonic mucin
      receptor was sensitive to periodate treatment suggesting the involvement of the
      carbohydrate portion of the mucin. Reduction and alkylation of mucin enhanced
      adherence probably by exposing buried binding sites. The monosaccharides present
      in mucins were ineffective as hapten inhibitors as was the lectin wheat germ
      agglutinin suggesting that the mucin receptor is a more complex one. This study
      identifies, for the first time, the presence of a specific Shigella-binding site
      on the carbohydrate portion of human colonic mucin, which is not present in rat
      colonic mucin or in rat/human small intestinal mucin.

PMID- 9546609
TI  - Expression of C/EBP alpha, beta and delta in fetal and postnatal subcutaneous
      adipose tissue.
AB  - The C/EBP (CCAAT/enhancer binding protein) family of transcription factors (C/EBP
      alpha, beta, and delta) has been implicated in the development and the metabolic
      regulation of adipocytes from in vitro studies, yet the function of these
      factors, particularly CEBP beta and delta, in vivo has not been characterized. To
      assess the role of these factors in vivo, subcutaneous adipose, tissue from fetal
      and postnatal pigs was examined for C/EBP alpha, beta, and delta expression in
      developing and mature adipocytes. Western blot analysis of fetal adipose tissue
      showed a progressive increase of C/EBP alpha expression in 50, 75 and 95 day old
      fetuses. C/EBP beta and delta proteins were not observed in fetal adipose tissue.
      These results were confirmed with immunohistochemical studies of fetal adipose
      showing enhanced C/EBP alpha expression in the nuclei of adipocytes and cells
      closely associated with adipose cell clusters from 75 and 95 day old fetuses. For
      the same tissues only light background staining with no differential enhancement
      was found for C/EBP beta and delta. In postnatal adipose tissue C/EBP alpha and
      C/EBP beta protein were expressed in both 8 day old postnatal and mature (180
      day) pigs. C/EBP delta reactive products were found in postnatal tissues however,
      their molecular weights were lower than that found in fetal pig liver. Our data
      suggest that adipose cell terminal differentiation proceeds in the pig fetus
      without the expression of C/EBP beta and delta and that these factors may have a
      more important role in fully differentiated adipose cells in postnatal tissue.

PMID- 9546610
TI  - Stimulatory effect of calcium administration on regucalcin mRNA expression is
      attenuated in the kidney cortex of rats ingested with saline.
AB  - The expression of calcium-binding protein regucalcin mRNA in the kidney cortex of
      rats ingested with saline was investigated. The alteration in regucalcin mRNA
      levels was analyzed by Northern blotting using liver regucalcin complementary DNA
      (0.9 kb of open reading frame). Rats were freely given saline as drinking water
      for 7 days. Regucalcin mRNA levels in the kidney cortex were suppressed by saline
      ingestion. When calcium chloride (10 mg Ca/100 g body weight) was
      intraperitoneally administered to rats ingested with saline for 7 days, the
      effect of calcium administration to increase regucalcin mRNA levels was weakened
      by saline ingestion. Such effect was also seen by the administration of 2.5 and 5
      mg Ca/100 g. Regucalcin mRNA levels in the kidney cortex of spontaneous
      hypertensive rats (SHR) were not appreciably increased by the administration of
      calcium (10 mg/100 g). Meanwhile, calcium content in the kidney cortex was
      significantly elevated by the administration of calcium (10 mg/100 g) to normal
      rats. This increase was weakened in saline-ingested rats. Moreover,
      Ca2+/calmodulin-dependent protein kinase activity in the cytosol of kidney cortex
      was significantly decreased by saline ingestion. These results suggest the
      possibility that saline ingestion-induced suppression of regucalcin mRNA
      expression in the kidney cortex is partly involved in the attenuation of Ca2+
      signalling.

PMID- 9546611
TI  - Expression of calcium-binding protein regucalcin mRNA in fetal rat liver is
      stimulated by calcium administration.
AB  - The expression of hepatic calcium-binding protein regucalcin mRNA in fetal rats
      was investigated. The alteration in regucalcin mRNA levels was analyzed by
      Northern blotting using liver regucalcin cDNA (0.9 kb with complete open reading
      frame). Hepatic regucalcin mRNA levels were progressively increased with fetal
      development; the mRNA was clearly expressed at 15 and 21 days of pregnancy but
      only slightly at the 8 days. Meanwhile, beta-actin mRNA levels in the fetal liver
      were remarkable at 8 and 15 days of pregnancy. The fetal liver regucalcin mRNA
      levels at 15 days of pregnancy were significantly decreased by overnight-fasting
      of maternal rats. The oral administration of calcium chloride (50 mg Ca/100 g
      body weight) to maternal rats at 15 days of pregnancy caused a remarkable
      elevation (about 2 fold) of regucalcin mRNA levels in the fetal liver; this
      increase was seen 60 and 180 min after the calcium administration. After birth,
      regucalcin mRNA was increasingly expressed in the livers of newborn and weanling
      rats, while hepatic beta-actin mRNA expression was not appreciably altered with
      increasing ages. These findings demonstrate that the expression of hepatic
      regucalcin mRNA is increased with fetal development, and that the gene expression
      may be stimulated by the ingestion of dietary calcium.

PMID- 9546612
TI  - Characterization of the reciprocal binding sites on human alpha-thrombin and
      factor XIII A-chain.
AB  - Solution- and solid-phase techniques were used to probe Factor XIII A-chain-alpha
      thrombin interactions. Alpha-thrombin activated Factor XIII more efficiently (Km
      = 0.83 +/- 0.08 x 10(-7) M; V/K = 14.90 +/- 3.20 x 10(-3) min(-1)) than beta
      thrombin (Km = 6.14 +/- 1.26 x 10(-7) M; V/K = 3.30 +/- 1.00 x 10(-3) min(-1)) or
      gamma-thrombin (Km = 6.25 +/- 1.15 x 10(-7) M; V/K = 3.00 +/- 0.80 x 10(-3) min(
      1)). Immobilized FPR-alpha-thrombin bound plasma Factor XIII (Kd = 0.17 +/- 0.04
      x 10(-7) M) > Factor XIIIa (Kd = 0.69 +/- 0.18 x 10(-7) M) > liver
      transglutaminase (Kd = 4.73 +/- 1.01 x 10(-7) M) > Factor XIII A-chain (Kd =
      49.00 +/- 9.40 x 10(-7) M). FPR-alpha-thrombin and alpha-thrombin also bound
      immobilized Factor XIII A-chain with affinities inversely related to protease
      activity: maximal binding at 1.36 x 10(-7) M and 13.6 x 10(-7) M, respectively.
      Plasma Factor XIII, transglutaminase, and dithiothreitol competitively inhibited
      Factor XIII A-chain binding to FPR-alpha-thrombin: IC50 = 1.0 x 10(-7) M, 3.0 x
      10(-6) M and 1.52 x 10(-4) M, respectively. Transglutaminase also inhibited
      Factor XIII binding to alpha-thrombin (IC50 = 2.0 x 10(-6) M). Thrombin-binding
      site was localized to G38-M731 fragment of Factor XIII A-chain, probably within
      homologous regions (N72-A493) of transglutaminase. R320-E579 of alpha-thrombin
      was Factor XIII A-chain binding site. Intra-B-chain disulfides in alpha-thrombin
      were essential for binding but not catalytic H363 or residues R382-N394 and R443
      G475. These studies propose a structural basis for Factor XIII activation,
      provide a regulatory mechanism for Factor XIIIa generation, and could eventually
      help in the development of new structure-based inhibitors of thrombin and Factor
      XIIIa.

PMID- 9546614
TI  - Tissue-specific binding of nuclear factors to the 5'-flanking region of the rat
      gene for calcium-binding protein regucalcin.
AB  - The existence of nuclear factors which bind to the 5'-flanking region of calcium
      binding protein regucalcin gene in rats was investigated. We previously reported
      that rat regucalcin mRNA is expressed in a highly tissue-specific manner; the
      mRNA was mainly present in the liver but only slightly in the kidney. When the
      nuclear proteins extracted from the liver and kidney of rats were used in the gel
      mobility shift assays, a protein-DNA complex was uniquely formed with the DNA
      fragment containing the upstream region from the first exon of rat regucalcin
      gene. On the other hand, this complex was not found by using the nuclear extracts
      from rat brain, spleen, and heart. The nuclear proteins of these extracts,
      however, could specifically bind to the DNA fragment containing the first exon
      region of rat regucalcin gene, although Northern blot analysis did not show
      detectable amount of regucalcin mRNA levels in rat brain, spleen, and heart. The
      present study demonstrates that the existence of nuclear protein components which
      bind to the regucalcin gene. These identified components may be involved in the
      tissue-specific regulation of regucalcin gene expression.

PMID- 9546613
TI  - Melatonin reduces the increase in 8-hydroxy-deoxyguanosine levels in the brain
      and liver of kainic acid-treated rats.
AB  - In the present study, the effect of melatonin on oxidative DNA damage induced by
      kainic acid (KA) treatment was investigated. 8-hydroxy-deoxyguanosine (8-OH-dG)
      is a main product of oxidatively damaged DNA and was used as the endpoint in
      these studies. The levels of 8-OH-dG were found to be elevated in the hippocampus
      and frontal cortex of rats treated with KA. These elevated levels were
      significantly reduced in animals that were co-treated with melatonin. Thus, there
      was no difference in 8-OH-dG levels in the brain of control rats compared to
      those treated with KA (10 mg/kg) plus melatonin (10 mg/kg). The levels of 8-OH-dG
      also increased in the liver of rats treated with KA. This rise in oxidatively
      damaged DNA was also prevented by melatonin administration. Melatonin's ability
      to reduce KA-induced increases in neural and hepatic 8-OH-dG levels presumably
      relates to its direct free radical scavenging ability and possibly to other
      antioxidative actions of melatonin.

PMID- 9546615
TI  - Streptozotocin-induced diabetes increases (Ca2+-Mg2+)-ATPase activity in hepatic
      plasma membranes of rats: involvement of protein kinase C.
AB  - The alteration in calcium transport in the liver of rats with streptozocin(STZ)
      diabetic state was investigated. STZ (6 mg/100 g body weight) was subcutaneously
      administered in rats, and 1 or 2 weeks later they were sacrificed by bleeding.
      STZ administration caused a remarkable elevation of serum glucose concentration.
      Liver calcium content was significantly increased by STZ administration. Hepatic
      plasma membrane (Ca2+-Mg2+)-ATPase activity was markedly elevated by STZ
      administration. This increase was completely abolished by the presence of
      staurosporine (10(-7)-10(-5) M), an inhibitor of protein kinase C, in the enzyme
      reaction mixture, suggesting an involvement of protein kinase C signalling.
      Moreover, the STZ-induced increase in liver plasma membrane (Ca2+-Mg2+)-ATPase
      activity was significantly raised by the presence of okadaic acid (10(-5) and 10(
      4) M). Meanwhile, the STZ-increased (Ca2+-Mg2+)-ATPase activity was not
      appreciably altered by the presence of anti-regucalcin IgG in the reaction
      mixture, indicating that the activatory protein regucalcin does not participate
      in the elevation of the enzyme activity. The present study demonstrates that STZ
      induced diabetes causes the increase in hepatic plasma membrane (Ca2+-Mg2+)
      ATPase activity of rats.

PMID- 9546616
TI  - Receptor-specific ligands distinguish natriuretic peptide receptors-A and -C in
      primate tissues.
AB  - Systemic clearance of atrial natriuretic peptide (ANP) is in part due to neutral
      endopeptidase (NEP) proteolysis and natriuretic peptide receptor-C (NPR-C)
      mediated endocytosis. Biological responses to ANP are primarily mediated by the
      membrane guanylyl cyclase-A/natriuretic peptide receptor-A (NPR-A). Analogs of
      ANP selective for NPR-A and/or resistant to NEP may have increased activity in
      those tissues where NPR-C and NEP are coexpressed with NPR-A. The analog of ANP
      termed vANP; [(R3D, G9T, R11S, M12L, G16R)ANP] is selective for human NPR-A with
      at least 10,000 fold reduction in affinity for human NPR-C. We report that rat
      NPR-A is insensitive to 10 nM vANP, demonstrating the limitations of this species
      in evaluating human therapeutic candidates. As an alternative approach we tested
      the binding and potency of receptor-selective and NEP-resistant ANP analogs in
      rhesus monkey tissues. Competition binding studies with a simplified version of
      vANP, sANP [(G9T, R11S, G16R)rANP], in rhesus monkey kidney and lung membrane
      preparations shows displacement of 125I-ANP from only a fraction of the total ANP
      receptor population, 30 and 85%, respectively. The remaining ANP binding sites
      can be occupied with the NPR-C selective ligand cANP(4-23). These data strongly
      suggest that only two classes of ANP receptor are present in these membrane
      preparations, NPR-A and NPR-C. The NEP resistant sANP derivative called
      sANP(TAPR) was 8 fold more potent (ED50 = 0.6 nM) than rANP (ED50 = 5 nM) in
      stimulating cGMP production in the lung membrane preparation. Our results
      demonstrate that the rhesus monkey natriuretic peptide receptors reflect the
      pharmacology of the human receptors, and that this species may be suitable to
      determine the role of NPR-C and NEP in peptide clearance and attenuating
      functional responses.

PMID- 9546617
TI  - The effect of dexamethasone treatment on the expression of the regulatory genes
      of ketogenesis in intestine and liver of suckling rats.
AB  - The influence of the injection of dexamethasone on ketogenesis in 12 day old
      suckling rats was studied in intestine and liver by determining mRNA levels and
      enzyme activity of the two genes responsible for regulation of ketogenesis:
      carnitine palmitoyl transferase I (CPT I) and mitochondrial HMG-CoA synthase.
      Dexamethasone produced a 2 fold increase in mRNA and activity of CPT I in
      intestine, but led to a decrease in mit. HMG-CoA synthase. In liver the mRNA
      levels and activity of both CPT I and mit. HMG-CoA synthase decreased. Comparison
      of these values with the ketogenic rate of both tissues following dexamethasone
      treatment suggests that mit. HMG-CoA synthase could be the main gene responsible
      for the regulation of ketogenesis in suckling rats. The changes produced in serum
      ketone bodies by dexamethasone, with a profile that is more similar to the
      ketogenic rate in the liver than that in the intestine, indicate that liver
      contributes more to ketone body synthesis in suckling rats. Two day treatment
      with dexamethasone produced no change in mRNA or activity levels for CPT I in
      liver or intestine. While mRNA levels for mit. HMG-CoA synthase changed little,
      the enzyme activity is decreased in both tissues.

PMID- 9546618
TI  - Pranidipine, a new 1,4-dihydropyridine calcium channel blocker, enhances cyclic
      GMP-independent nitric oxide-induced relaxation of the rat aorta.
AB  - Pranidipine, a new calcium channel blocker, prolonged endothelium-dependent
      relaxation induced by acetylcholine in an aortic ring preparation, contracted
      with prostaglandin F2alpha. This action was not shared by amlodipine. The effect
      was not modified by indomethacin, suggesting that the action of pranidipine does
      not involve prostanoid metabolism. N(G)-nitro-L-arginine completely prevented the
      action of Pranidipine. The drug affected neither nitric oxide (NO) synthase
      activity nor the level of cyclic GMP in the vessel. Pranidipine did not affect
      the sensitivity of the contractile proteins to calcium. Pranidipine also did not
      alter cyclic GMP-induced relaxation in alpha-toxin-skinned vascular preparations.
      Pranidipine also prolonged glyceryl trinitrate-induced relaxation in the
      endothelium denuded rat aorta. Furthermore, pranidipine enhanced relaxation of
      the aorta induced by glyceryl trinitrate even in the presence of methylene blue,
      a guanylyl cyclase inhibitor. This action was not modified by iberiotoxin or by
      charybdotoxin, two inhibitors of the calcium-activated potassium channel. The
      results strongly suggest that pranidipine enhances cyclic GMP-independent NO
      induced relaxation of smooth muscle by a mechanism other than through NO-induced
      hyperpolarization. These effects were in direct contrast to amlodipine, another
      new 1,4-dihydropyridine calcium antagonist.

PMID- 9546619
TI  - Intestinal mucosal lipid peroxidation and absorptive function in Salmonella
      typhimurium mediated intestinal infection.
AB  - S. typhimurium infection is associated with neutrophil infiltration within the
      intestinal mucosa. Neutrophil activation provides a major source of reactive
      oxygen species (ROS). The mucosal pathology of S. typhimurium infection may be in
      part due to the excessive production of these reactive species. This study was
      carried out to investigate if ROS play a role in mediating the changes in the
      structural components and functional properties of brush border membrane (BBM) in
      rats during S. typhimurium infection. This was done by determining the changes in
      the BBM extent of lipid peroxidation and absorptive function. A significant
      increase in the extent of lipid peroxidation of BBM during S. typhimurium
      infection was observed as judged by malondialdehyde (MDA) and conjugated diene
      formation and depletion of alpha-tocopherol and protein associated thiol groups.
      A significant decrease in the BBMV (brush border membrane vesicle) transport of
      amino acids was also observed. However there was no change in the transport of D
      glucose. The decrease in amino acid transport further led to a significant
      decrease in the enterocyte level of protein synthesis. Exposure of BBMV to a free
      radical donor, cumene hydroperoxide, also led to an increase in the extent of
      lipid peroxidation and a decrease in the amino acid transport. Possibly ROS might
      play a significant role in mediating the mucosal damage during S. typhimurium
      infection.

PMID- 9546620
TI  - Is a dietary n-3 fatty acid supplement able to influence the cardiac effect of
      the psychological stress?
AB  - Epidemiological studies suggest that n-3 polyunsaturated fatty acids (PUFA) are
      involved in the prevention of cardiovascular disease. Stress is known to increase
      the incidence of CVD and the present study was realised to evaluate some
      physiological and biochemical effects of dietary docosahexaenoic acid (DHA) in
      male Wistar rats subjected to a psycho social stress. Rats were fed for 8 weeks a
      semi-purified diet containing 10% of either sunflower seed oil or the same oil
      supplemented with DHA. This food supply represented 50% of their daily
      requirement. The remaining 50% were supplied as 45 mg food pellets designed to
      induce stress in rats by an intermittent-feeding schedule process. The control
      group (n = 12) was fed the equivalent food ration as a single daily feeding. The
      physiological cardiovascular parameters were recorded by telemetry through a
      transmitter introduced in the abdomen. At the end of the experimentation, the
      heart and adrenals were withdrawn and the fatty acid composition and the
      catecholamine store were determined. Dietary DHA induced a pronounced alteration
      of the fatty acid profile of cardiac phospholipids (PL). The level of all the n-6
      PUFAs was reduced while 22:6 n-3 was increased. The stress induced a significant
      increase in heart rate which was not observed in DHA-fed group. The time
      evolution of the systolic blood pressure was not affected by the stress and was
      roughly similar in the stressed rats of either dietary group. Conversely, the
      systolic blood pressure decreased in the unstressed rats fed DHA. Similar data
      were obtained for the diastolic blood pressure. The beneficial effect of DHA was
      also observed on cardiac contractility, since the dP/dt(max) increase was
      prevented in the DHA-fed rats. The stress-induced modifications were associated
      with an increase in cardiac noradrenaline level which was not observed in DHA-fed
      rats. The fatty acid composition of adrenals was significantly related to the
      fatty acid intake particularly the neutral lipid fraction (NL) which incorporated
      a large amount of DHA. Conversely, n-3 PUFAs were poorly incorporated in adrenal
      phospholipids. Moreover the NL/PL ratio was significantly increased in the DHA
      fed rats. The amount of adrenal catecholamines did not differ significantly
      between the groups. These results show that a supplementation of the diet with
      DHA induced cardiovascular alterations which could be detected in conscious
      animals within a few weeks. These alterations were elicited by a reduced heart
      rate and systolic and diastolic blood pressure.

PMID- 9546621
TI  - Stimulation of MAP kinase and S6 kinase by vanadium and selenium in rat
      adipocytes.
AB  - To explore the mechanism underlying the insulin-mimetic actions of vanadium and
      selenium we examined their effects on the mitogen activated protein/myelin basic
      protein kinases (MAPK) and ribosomal S6 protein kinases, which are among the best
      characterized of the kinases that comprise the phosphorylation cascade in insulin
      signal transduction. We observed a transient activation of MAPK and S6 kinases by
      insulin in rat adipocytes, while both sodium selenate and vanadyl sulphate
      produced prolonged activation of the kinases. Vanadyl sulphate stimulated the
      activity of MAPK and S6 kinase by as much as 6 fold and 15 fold, respectively.
      Pretreatment of the cells with genistein did not affect the activation of MAPK by
      insulin, but partially blocked the effects of sodium selenate and vanadyl
      sulphate. Genistein did not change the activation of S6 kinase by insulin, but
      blocked the activation in vanadyl sulphate- and sodium selenate-treated-cells,
      suggesting that a genistein sensitive tyrosine kinase may be involved in the
      activation by these two compounds. Rapamycin, a specific inhibitor of the p70s6k
      isoform of S6 kinase, partially reduced the activation of S6 kinase activity by
      sodium selenate, indicating a role for this kinase in the overall activity of the
      S6 kinase in sodium selenate-treated cells. A similar trend was noted in vanadyl
      sulphate-treated cells. Thus, this study supports the involvement of MAPK and S6
      kinases in the insulin-mimetic actions of vanadium and selenium.

PMID- 9546622
TI  - Anabolic effect of genistein and genistin on bone metabolism in the femoral
      metaphyseal tissues of elderly rats: the genistein effect is enhanced by zinc.
AB  - The effect of genistein and genistin on bone components in the femoral
      metaphyseal tissues obtained from elderly female rats was investigated in vitro.
      The metaphyseal tissues were cultured for 24 h in a medium containing either
      vehicle, genistein (10(-8)-10(-5) M) or genistin (10(-7)-10(-5) M). The presence
      of genistein or genistin caused a significant increase in alkaline phosphatase
      activity, deoxyribonucleic acid (DNA) and calcium contents in the metaphyseal
      tissues. The effect of genistein was greater than that of genistin. The bone
      components increased by genistein (10(-5) M) or genistin (10(-5) M) were
      completely blocked by the presence of cycloheximide (10(-6) M). The presence of
      zinc sulfate (10(-5) M) caused a significant increase in the genistein (10(-5) M)
      elevated alkaline phosphatase activity, DNA and calcium contents. The enhancement
      with zinc was not seen by genistin (10(-5) M). The stimulatory effect of zinc on
      the genistein-induced increase in bone components of the metaphyseal tissues was
      completely blocked by the presence of cycloheximide (10(-6) M). The present
      results suggest that genistein and genistin have an anabolic effect on bone
      metabolism in the femoral-metaphyseal tissues of elderly rats, and that the
      genistein effect is enhanced by zinc, an essential trace element.

PMID- 9546623
TI  - Human platelets contain a novel 47 kDa thiol-oxidase having affinity for genomic
      sterol-regulatory sequence.
AB  - The present study provides evidence to support that human platelets possess a 47
      kDa dual functional molecule having thiol-oxidase activity as well as high
      affinity for the SRE sequence in the human genome. On the basis of these as well
      as earlier results, we propose that Receptor 'Ck' dependent regulation of this
      dual functional 47 kDa molecule may provide a mechanism for the maintenance of
      cellular cholesterol homeostasis. Further, this mechanism may also explain the
      molecular basis of cholesterol-feedback lesion observed under premalignant
      conditions.

PMID- 9546624
TI  - Glutathione involvement on the intestinal Na+-dependent D-glucose active
      transporter.
AB  - Glutathione and its related enzymes are present in intestinal epithelium.
      Depletion or alteration of glutathione levels have been related to different
      physiological and pathological conditions. Glutathione also seems to be related
      to the regulation of some protein activities. The present study, by in vivo
      experiments, shows a specific relationship between D-glucose Na+-dependent active
      transporter activity in rat intestine brush-border membranes and reduced
      glutathione/oxidized glutathione ratio levels. Changes of the kinetic parameters
      show that an increase of this ratio is related to an increase of the affinity of
      glucose for its binding sites and a higher transport capacity of the transporter.
      Neither alteration in the activity of other substrate transport systems nor
      change in the specific activity of the key enzymes related to glutathione and
      glucose metabolism are found. These findings suggest the possibility that D
      glucose transporter activity is modulated through the change in the redox status
      of glutathione.

PMID- 9546625
TI  - Phosphopeptides derived from in vitro phosphorylated E. coli RNA polymerase bind
      to DNA and affect DNA transcription.
AB  - E. Coli RNA polymerase was phosphorylated with protein kinase CKII and allowed to
      bind to pBR322. After digestion of the RNA polymerase-pBR322 complex with
      proteinase K, the phosphopeptides that remained bound to DNA were extracted and
      analyzed. These phosphopeptides are able to bind again to DNA and to inhibit
      transcription.

PMID- 9546627
TI  - Differential regulation in the heart of mitochondrial carnitine
      palmitoyltransferase-I muscle and liver isoforms.
AB  - Carnitine palmitoyltransferase-I (CPT-I) plays a crucial role in regulating
      cardiac fatty acid oxidation which provides the primary source of energy for
      cardiac muscle contraction. CPT-I catalyzes the transfer of long chain fatty
      acids into mitochondria and is recognized as the primary rate controlling step in
      fatty acid oxidation. Molecular cloning techniques have demonstrated that two CPT
      I isoforms exist as genes encoding the 'muscle' and 'liver' enzymes. Regulation
      of fatty acid oxidation rates depends on both short-term regulation of enzyme
      activity and long-term regulation of enzyme synthesis. Most early investigations
      into metabolic control of fatty acid oxidation at the CPT-I step concentrated on
      the hepatic enzyme which can be inhibited by malonyl-CoA and can undergo dramatic
      amplification or reduction of its sensitivity to inhibition by malonyl-CoA. The
      muscle CPT-I is inherently more sensitive to malonyl-CoA inhibition but has not
      been found to undergo any alteration of its sensitivity. Short-term control of
      activity of muscle CPT-I is apparently regulated by malonyl-CoA concentration in
      response to fuel supply (glucose, lactate, pyruvate and ketone bodies). The liver
      isoform is the only CPT-I enzyme present in the mitochondria of liver, kidney,
      brain and most other tissues while muscle CPT-I is the sole isoform expressed in
      skeletal muscle as well as white and brown adipocytes. The heart is unique in
      that it contains both muscle and liver isoforms. Liver CPT-I is highly expressed
      in the fetal heart, but at birth its activity begins to decline whereas the
      muscle isoform, which is very low at birth, becomes the predominant enzyme during
      postnatal development. In this paper, the differential regulation of the two CPT
      I isoforms at the protein and the gene level will be discussed.

PMID- 9546628
TI  - Carnitine deficiency-induced cardiomyopathy.
AB  - The results of clinical and animal studies suggest that a short term period of
      moderate secondary carnitine deficiency, in and of itself, does not have a major
      effect on the cardiac contractile function, although substrate oxidation may be
      altered. However, with longer durations of carnitine deficiency, alterations
      occur within the heart that may result in impaired contractile performance,
      particularly at high workloads. At this point, the mechanisms responsible for the
      cardiac depression are uncertain. We hypothesize that the alterations in
      substrate metabolism produced by the carnitine deficient state results in
      inadequate ATP production under high workload conditions which result in impaired
      cardiac contractile performance. Carnitine deficiency may also induce a number of
      changes in gene expression of key enzymes required for normal cardiac contractile
      function and metabolism.

PMID- 9546626
TI  - Glucose and glycogen utilisation in myocardial ischemia--changes in metabolism
      and consequences for the myocyte.
AB  - Experimentally, enhanced glycolytic flux has been shown to confer many benefits
      to the ischemic heart, including maintenance of membrane activity, inhibition of
      contracture, reduced arrhythmias, and improved functional recovery. While at
      moderate low coronary flows, the benefits of glycolysis appear extensive, the
      controversy arises at very low flow rates, in the absence of flow; or when
      glycolytic substrate may be present in excess, such that high glucose
      concentrations with or without insulin overload the cell with deleterious
      metabolites. Under conditions of total global ischemia, glycogen is the only
      substrate for glycolytic flux. Glycogenolysis may only be protective until the
      accumulation of metabolites (lactate, H+, NADH, sugar phosphates and Pi )
      outweighs the benefit of the ATP produced. The possible deleterious effects
      associated with increased glycolysis cannot be ignored, and may explain some of
      the controversial findings reported in the literature. However, an optimal
      balance between the rate of ATP production and rate of accumulation of
      metabolites (determined by the glycolytic flux rate and the rate of coronary
      washout), may ensure optimal recovery. In addition, the effects of glucose
      utilisation must be distinguished from those of glycogen, differences which may
      be explained by functional compartmentation within the cell.

PMID- 9546629
TI  - Fatty acid-binding proteins in the heart.
AB  - Long-chain fatty acids are important fuel molecules for the heart, their
      oxidation in mitochondria providing the bulk of energy required for cardiac
      functioning. The low solubility of fatty acids in aqueous solutions impairs their
      cellular transport. However, cardiac tissue contains several proteins capable of
      binding fatty acids non-covalently. These fatty acid-binding proteins (FABPs) are
      thought to facilitate both cellular uptake and intracellular transport of fatty
      acids. The majority of fatty acids taken up by the heart seems to pass the
      sarcolemma through a carrier-mediated translocation mechanism consisting of one
      or more membrane-associated FABPs. Intracellular transport of fatty acids towards
      sites of metabolic conversion is most likely accomplished by cytoplasmic FABPs.
      In this review, the roles of membrane-associated and cytoplasmic FABPs in cardiac
      fatty acid metabolism under (patho)physiological circumstances are discussed.

PMID- 9546630
TI  - Metabolic disturbances in diabetic cardiomyopathy.
AB  - It has been established that diabetes results in a cardiomyopathy, and increasing
      evidence suggests that an altered substrate supply and utilization by cardiac
      myocytes could be the primary injury in the pathogenesis of this specific heart
      muscle disease. For example, in diabetes, glucose utilization is insignificant,
      and energy production is shifted almost exclusively towards beta-oxidation of
      free fatty acids (FFA). FFA's are supplied to cardiac cells from two sources:
      lipolysis of endogenous cardiac triglyceride (TG) stores, or from exogenous
      sources in the blood (as free acid bound to albumin or as TG in lipoproteins).
      The approximate contribution of FFA from exogenous or endogenous sources towards
      beta-oxidation in the diabetic heart is unknown. In an insulin-deficient state,
      adipose tissue lipolysis is enhanced, resulting in an elevated circulating FFA.
      In addition, hydrolysis of the augmented myocardial TG stores could also lead to
      high tissue FFA. Whatever the source of FFA, their increased utilization may have
      deleterious effects on myocardial function and includes the abnormally high
      oxygen requirement during FFA metabolism, the intracellular accumulation of
      potentially toxic intermediates of FFA, a FFA-induced inhibition of glucose
      oxidation, and severe morphological changes. Therapies that target these
      metabolic aberrations in the heart during the early stages of diabetes could
      potentially delay or impede the progression of more permanent sequelae that could
      ensue from otherwise uncontrolled derangements in cardiac metabolism.

PMID- 9546631
TI  - Diabetes mellitus and cardiac function.
AB  - Cardiovascular complications are the most common causes of morbidity and
      mortality in diabetic patients. Coronary atherosclerosis is enhanced in
      diabetics, whereas myocardial infarction represents 20% of deaths of diabetic
      subjects. Furthermore, re-infarction and heart failure are more common in the
      diabetics. Diabetic cardiomyopathy is characterized by an early diastolic
      dysfunction and a later systolic one, with intracellular retention of calcium and
      sodium and loss of potassium. In addition, diabetes mellitus accelerates the
      development of left ventricular hypertrophy in hypertensive patients and
      increases cardiovascular mortality and morbidity. Treating the cardiovascular
      problems in diabetics must be undertaken with caution. Special consideration must
      be given with respect to the ionic and metabolic changes associated with
      diabetes. For example, although ACE inhibitors and calcium channel blockers are
      suitable agents, potassium channel openers cause myocardial preconditioning and
      decrease the infarct size in animal models, but they inhibit the insulin release
      after glucose administration in healthy subjects. Furthermore, potassium channel
      blockers abolish myocardial preconditioning and increase infarct size in animal
      models, but they protect the heart from the fatal arrhythmias induced by ischemia
      and reperfusion which may be important in diabetes. For example, diabetic
      peripheral neuropathy usually presents with silent ischemia and infarction.
      Mechanistically, parasympathetic cardiac nerve dysfunction, expressed as
      increased resting heart rate and decreased respiratory variation in heart rate,
      is more frequent than the sympathetic cardiac nerve dysfunction expressed as a
      decrease in the heart rate rise during standing.

PMID- 9546633
TI  - The role of glucose metabolism in a pig heart model of short-term hibernation.
AB  - Previously, we reported, alterations in glucose metabolism in a 4 day model of
      chronic coronary stenosis similar to those described in patients with hibernating
      hearts. The purpose of this study was 2 fold: (1) to identify whether an acute
      model of mild, sustained ischemia could effect similar changes, and (2) to
      determine the effects of pharmacological inhibition of glycolysis. In the first
      group, extracorporeally perfused, intact pig hearts were subjected to 85 min of a
      40% reduction in left anterior descending (LAD) coronary arterial blood flow. A
      second group was subjected to the same protocol, except after 40 min of LAD
      regional ischemia, iodoacetate (IAA) was administered to block glycolysis.
      Ischemia reduced MVO2 by 10% in both groups with a further 20% reduction noted
      following IAA treatment. Regional systolic shortening was reduced nearly 50% by
      ischemia and decreased an additional 40% following treatment with IAA. Glycolysis
      was increased by over 700% with ischemia in the first group. IAA caused a 3 fold
      reduction in glycolysis as compared to the preceding ischemic period and
      inhibited lactate production. Fatty acid metabolism was significantly reduced by
      ischemia in the first group, but was not reduced in the IAA group. Activity of
      creatine kinase associated with myofibrils was reduced and may have contributed
      to the contractile dysfunction. In conclusion, this acute model of short-term
      hibernation demonstrates several metabolic changes previously reported in chronic
      hibernation and may prove useful in determining mechanisms of substrate
      utilization in simulated conditions of chronic coronary stenosis and hibernation.

PMID- 9546632
TI  - Phospholipase A2-mediated hydrolysis of cardiac phospholipids: the use of
      molecular and transgenic techniques.
AB  - Under pathophysiological conditions, like myocardial ischemia and reperfusion,
      cardiac phospholipid homeostasis is severely disturbed, resulting in a net
      degradation of phospholipids and the accumulation of degradation products, such
      as lysophospholipids and (non-esterified) fatty acids. The derangements in
      phospholipid metabolism are thought to be involved in the sequence of events
      leading to irreversible myocardial injury. The net degradation of phospholipids
      as observed during myocardial ischemia may result from increased hydrolysis
      and/or reduced resynthesis, while during reperfusion hydrolysis is likely to
      prevail in this net degradation. Several studies indicate that the activation of
      phospholipases A2 plays an important role in the hydrolysis of phospholipids. In
      this review current knowledge regarding the potential role of the different types
      of phospholipases A2 in ischemia and reperfusion-induced damage is being
      evaluated. Furthermore, it is indicated how recent advances in molecular
      biological techniques could be helpful in determining whether disturbances in
      phospholipid metabolism indeed play a crucial role in the transition from
      reversible to irreversible myocardial ischemia and reperfusion-induced injury,
      the knowledge of which could be of great therapeutic relevance.

PMID- 9546634
TI  - Glucose metabolism, H+ production and Na+/H+-exchanger mRNA levels in ischemic
      hearts from diabetic rats.
AB  - Glycolysis uncoupled from glucose oxidation is a major reason for the
      intracellular acidosis that occurs during severe myocardial ischemia. The
      imbalance between glycolysis and glucose oxidation, and the resultant H+ produced
      from glycolytically derived ATP hydrolysis in the diabetic rat heart is the focus
      of this study. Isolated working hearts from 6 week streptozotocin diabetic rat
      hearts were perfused with 11 mM glucose and 1.2 mM palmitate and subjected to a
      25 min period of global ischemia. A second series of experiments were also
      performed in which hearts from control, diabetic, and islet-transplanted diabetic
      rats were subjected to a 30 min aerobic perfusion, followed by a 60 min period of
      low-flow ischemia (coronary flow = 0.5 ml/min) and 30 min of aerobic reperfusion.
      H+ production from glucose metabolism was measured throughout the two protocols
      by simultaneous measurement of glycolysis and glucose oxidation using perfusate
      labelled with [5-3H/U-14C]-glucose. Rates of H+ production were calculated by
      measuring the difference between glycolysis and glucose oxidation. The H+
      production throughout the perfusion was generally lower in diabetic rat hearts
      compared to control hearts, while islet-transplantation of diabetic rats
      increased H+ production to rates similar to those seen in control hearts. This
      occurred primarily due to a dramatic increase in the rates of glycolysis. Despite
      the difference in H+ production between control, diabetic and islet-transplanted
      diabetic rat hearts, no difference in mRNA levels of the cardiac Na+/H+-exchanger
      (NHE-1) was seen. This suggests that alterations in the source of protons (i.e.
      glucose metabolism) are as important as alterations in the fate of protons, when
      considering diabetes-induced changes in cellular pH. Furthermore, our data
      suggests that alterations in Na+/H+-exchange activity in the diabetic rat heart
      occur at a post-translational level, possibly due to direct alterations in the
      sarcolemmal membranes.

PMID- 9546635
TI  - Regulation of carbohydrate and fatty acid utilization by L-carnitine during
      cardiac development and hypoxia.
AB  - This study is designed to investigate whether substrate preference in the
      myocardium during the neonatal period and hypoxia-induced stress is controlled
      intracellularly or by extracellular substrate availability. To determine this,
      the effect of exogenous L-carnitine on the regulation of carbohydrate and fatty
      acid metabolism was determined during cardiac stress (hypoxia) and during the
      postnatal period. The effect of L-carnitine on long chain (palmitate) and medium
      chain (octonoate) fatty acid oxidation was studied in cardiac myocytes isolated
      from less than 24 h old (new born; NB), 2 week old (2 week) and hypoxic 4 week
      old (HY) piglets. Palmitate oxidation was severely decreased in NB cells compared
      to those from 2 week animals (0.456+/-0.04 vs. 1.207+/-0.52 nmol/mg protein/30
      min); surprisingly, cells from even older hypoxic animals appeared shifted toward
      the new born state (0.695+/-0.038 nmol/mg protein/30 min). Addition of L
      carnitine to the incubation medium, which stimulates carnitine palmitoyl
      transferase I (CPTI) accelerated palmitate oxidation 3 fold in NB and
      approximately 2 fold in HY and 2 week cells. In contrast, octanoate oxidation
      which was greater in new born myocytes than in 2 week cells, was decreased by L
      carnitine suggesting a compensatory response. Furthermore, oxidation of
      carbohydrates (glucose, pyruvate, and lactate) was greatly increased in new born
      myocytes compared to 2 week and HY cells and was accompanied by a parallel
      increase in pyruvate dehydrogenase (PDH) activity. The concentration of malonyl
      CoA, a potent inhibitor of CPTI was significantly higher in new born heart than
      at 2 weeks. These metabolic data taken together suggest that intracellular
      metabolic signals interact to shift from carbohydrate to fatty acid utilization
      during development of the myocardium. The decreased oxidation of palmitate in NB
      hearts probably reflects decreased intracellular L-carnitine and increased
      malonyl-CoA concentrations. Interestingly, these data further suggest that the
      cells remain compliant so that under stressful conditions, such as hypoxia, they
      can revert toward the neonatal state of increased glucose utilization.

PMID- 9546636
TI  - Identification of nucleoside transport binding sites in the human myocardium.
AB  - The role of nucleoside transport in ischemia-reperfusion injury and arrhythmias
      has been well documented in various animal models using selective blockers.
      However, clinical application of nucleoside transport inhibitors remains to be
      demonstrated in humans. It is not known whether human heart has nucleoside
      transport similar to that of animals. The aim of this study is to
      pharmacologically identify the presence of nucleoside transport binding sites in
      the human myocardium compared to animals. Myocardial tissue was obtained from
      guinea pig left and right ventricle, canine left ventricle, human intraoperative
      right atrium and human cadaveric right atrium and right and left ventricles.
      Myocardial preparations were obtained from tissue samples after homogenized and a
      differential centrifugation. Equilibrium binding assays were performed using [3H]
      p-nitrobenzylthioinosine (NBMPR) at room temperature in the presence or absence
      of non-radioactive NBMPR or other nucleoside transport blockers such as p
      nitrobenzylthioguanosine dipyridamole, lidoflazine, papaverin, adenosine and
      doxorubcine. From saturation curves and inhibition kinetics, we determined the
      relative maximal binding (Bmax) and dissociation constant (Kd) of [3H]-NBMPR
      binding of human myocardial preparations. Results demonstrated that the fresh
      human myocardial preparations have a specific binding site for NBMPR with a Bmax
      of 283+/-32 fmol/mg protein and Kd of 0.56+/-0.12 nM. These values are lower than
      those obtained from guinea pigs (Bmax = 1440+/-187 fmol/mg protein and Kd =
      0.21+/-0.03 nM) and canine atrium (Bmax 594+/-73 fmol/mg protein, and Kd = 1.12+/
      0.22 nM). Displacement kinetics studies revealed the relative potencies (of
      certain unrelated drugs as follow: p-nitrobenzylthioguanosine > dipyridamole >
      lidoflazine > pavaverine > Diltazam > adenosine > doxyrubicin. It is concluded
      that human myocardium contains an active nucleoside transport site which may play
      a crucial role in post-ischemic reperfusion-mediated injury in a wide spectrum of
      ischemic syndromes.

PMID- 9546637
TI  - Mutagenesis and characterization of specific residues in fatty acid ethyl ester
      synthase: a gene for alcohol-induced cardiomyopathy.
AB  - Fatty acid ethyl ester synthase-III metabolizes both ethanol and carcinogens.
      Structure-function studies of the enzyme have not been performed in relation to
      site specific mutagenesis. In this study, three residues (Gly 32, Cys 39 and His
      72) have been mutated to observe their role in enzyme activity. Gly to Gln, Cys
      to Trp and His to Ser mutations did not affect fatty acid ethyl ester synthase
      activity, but His to Ser mutant had less than 9% of control glutathione S
      transferase activity. The apparent loss of transferase activity reflected a 28
      fold weaker binding constant for glutathione. Thus, this study indicates that Gly
      and Cys may not be important for synthase or transferase activities however,
      histidine may play a role in glutathione binding, but it is not an essential
      catalytic residue of glutathione S-transferase or for fatty acid ethyl ester
      synthase activity.

PMID- 9546638
TI  - Palmitate oxidation by the mitochondria from volume-overloaded rat hearts.
AB  - In this work, an attempt was made to identify the reasons of impaired long-chain
      fatty acid utilization that was previously described in volume-overloaded rat
      hearts. The most significant data are the following: (1) The slowing down of long
      chain fatty acid oxidation in severely hypertrophied hearts cannot be related to
      a feedback inhibition of carnitine palmitoyltransferase I from an excessive
      stimulation of glucose oxidation since, because of decreased tissue levels of L
      carnitine, glucose oxidation also declines in volume-overloaded hearts. (2)
      While, in control hearts, the estimated intracellular concentrations of free
      carnitine are in the range of the respective Km of mitochondrial CPT I, a kinetic
      limitation of this enzyme could occur in hypertrophied hearts due to a 40%
      decrease in free carnitine. (3) The impaired palmitate oxidation persists upon
      the isolation of the mitochondria from these hearts even in presence of
      saturating concentrations of L-carnitine. In contrast, the rates of the
      conversion of both palmitoyl-CoA and palmitoylcarnitine into acetyl-CoA are
      unchanged. (4) The kinetic analyses of palmitoyl-CoA synthase and carnitine
      palmitoyltransferase I reactions do not reveal any differences between the two
      mitochondrial populations studied. On the other hand, the conversion of palmitate
      into palmitoylcarnitine proves to be substrate inhibited already at physiological
      concentrations of exogenous palmitate. The data presented in this work
      demonstrate that, during the development of severe cardiac hypertrophy, a
      fragilization of the mitochondrial outer membrane may occur. The functional
      integrity of this membrane seems to be further deteriorated by increasing
      concentrations of free fatty acids which gives rise to an impaired cooperation
      between palmitoyl-CoA synthase and carnitine palmitoyltransferase I. In intact
      myocardium, the utilization of the in situ generated palmitoyl-CoA can be further
      slowed down by decreased intracellular concentrations of free carnitine.

PMID- 9546639
TI  - Effects of phosphodiesterase inhibitors on glucose utilization in isolated
      cardiac myocytes.
AB  - The phosphodiesterase (PDE) inhibitor, enoximone, enhances the oxidation of fatty
      acids in cardiac myocytes. Since carbohydrate oxidation is tightly coupled and
      inversely related in cardiac tissue to fatty acid oxidation, this study was
      designed to investigate enoximone's effects on glucose metabolism in the heart.
      To determine if enoximone alters this reciprocal relationship, the effects of
      enoximone on [U-14C]glucose and [2-14C]pyruvate oxidation were determined in
      isolated cardiac myocytes. The effect of PDE inhibitors was also examined on
      pyruvate dehydrogenase complex (PDH) activity, a key component of oxidative
      glucose metabolism. Two PDE inhibitors, enoximone and milrinone, decreased PDH
      activity by 69 and 64%, respectively at 0.5 mM. This inhibition of PDH activity
      by enoximone was completely reversed after removing enoximone from the myocyte
      medium. PDH activity was unaffected by agents which alter cyclic nucleotide
      signaling: cGMP, dibutyryl cyclic AMP, and AMP. The effect of enoximone on [2
      14C]pyruvate oxidation was similar to that on PDH. Interestingly, the oxidation
      of glucose was decreased 35% by 0.5 mM enoximone. In isolated rat heart
      mitochondria (RHM), enoximone decreased PDH activity by 37%. These studies
      suggest that PDE inhibitors decrease carbohydrate utilization by inhibiting the
      PDH complex in the heart. The inhibition of PDH by PDE inhibitors appears
      unrelated to their effects on cAMP or cGMP. This inhibition of PDH by PDE
      inhibitors may occur, at least in part, secondary to stimulating fatty acid
      oxidation.

PMID- 9546640
TI  - Energy metabolism and mechanical recovery after cardioplegia in moderately
      hypertrophied rats.
AB  - It is well established that severe hypertrophy induces metabolic and structural
      changes in the heart which result in enhanced susceptibility to ischemic damage
      during cardioplegic arrest while much less is known about the effect of
      cardioplegic arrest on moderately hypertrophied hearts. The aim of this study was
      to elucidate the differences in myocardial high energy phosphate metabolism and
      in functional recovery after cardioplegic arrest and ischemia in mildly
      hypertrophied hearts, before any metabolic alterations could be shown under
      baseline conditions. Cardiac hypertrophy was induced in rats by constriction of
      the abdominal aorta resulting in 20% increase in heart weight/body weight ratio
      (hypertrophy group) while sham operated animals served as control. In both
      groups, isolated hearts were perfused under normoxic conditions for 40 min
      followed by infusion of St.Thomas' Hospital No. 1 cardioplegia and 90 min
      ischemia at 25 degrees C with infusions of cardioplegia every 30 min. The changes
      in ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) were followed by 31P
      nuclear magnetic resonance (NMR) spectroscopy. Systolic and diastolic function
      was assessed with an intraventricular balloon before and after ischemia. Baseline
      concentrations of PCr, ATP and Pi as well as coronary flow and cardiac function
      were not different between the two groups. However, after cardioplegic arrest PCr
      concentration increased to 61.8+/-4.9 micromol/g dry wt in the control group and
      to 46.3+/-2.8 micromol/g in hypertrophied hearts. Subsequently PCr, pH and ATP
      decreased gradually, concomitant with an accumulation of Pi in both groups. PCr
      was transiently restored during each infusion of cardioplegic solution while Pi
      decreased. PCr decreased faster after cardioplegic infusions in hypertrophied
      hearts. The most significant difference was observed during reperfusion: PCr
      recovered to its pre-ischemic levels within 2 min following restoration of
      coronary flow in the control group while similar recovery was observed after 4
      min in the hypertrophied hearts. A greater deterioration of diastolic function
      was observed in hypertrophied hearts. Moderate hypertrophy, despite absence of
      metabolic changes under baseline conditions could lead to enhanced functional
      deterioration after cardioplegic arrest and ischemia. Impaired energy metabolism
      resulting in accelerated high energy phosphate depletion during ischemia and
      delayed recovery of energy equilibrium after cardioplegic arrest observed in
      hypertrophied hearts could be one of the underlying mechanisms.

PMID- 9546641
TI  - Role of nucleoside transport and purine release in a rabbit model of myocardial
      stunning.
AB  - Previously, we have demonstrated the role of nucleoside transport and purine
      release in post-ischemic reperfusion injury (myocardial stunning) in several
      canine models of ischemia. Since rabbits are deficient of xanthine oxidase, it is
      not known whether selective blockade of purine release is beneficial in a rabbit
      model of coronary artery occlusion and reperfusion (stunning). Therefore, we
      determined the hemodynamic and metabolic correlates in response to myocardial
      stunning in the presence or absence of selective nucleoside transport blocker (p
      nitrobenzylthioinosine, NBMPR) and adenosine deaminase inhibitor (erythro-9-(2
      hydroxy-3-nonyl)adenine, EHNA). Sixty adult anaesthetized rabbits were surgically
      prepared for hemodynamic measurements. After stabilization period, the left
      anterior descending coronary artery was occluded for 15 min and reperfused for 30
      min. Transmural myocardial biopsies were obtained from the ischemic LAD area and
      from the non-ischemic posterior (circumflex, CFX) segment of the myocardium.
      Rabbits (n = 60) were randomly assigned to either the control or the EHNA/NBMPR
      treated group (n = 30 each). Each group was further divided to either functional
      or metabolic groups (n = 15 each subgroup). Each animal received intravenously 30
      ml of either a vehicle solution or 100 M EHNA and 25 M NBMPR 10 min before
      ischemia. Although administration of EHNA/NBMPR did not affect the heart rate, it
      did cause mild hypotension (about 20-30%). Fifteen minutes of LAD occlusion
      resulted in significant ATP depletion and concomitant accumulation of nucleosides
      in both groups (p < 0.05 vs. baseline and non-ischemic CFX segment). AMP was
      higher in the LAD compared to the CFX segment. Significant accumulation of
      adenosine was observed in the treated group compared to the control group. It is
      concluded that EHNA/NBMPR induced site specific entrapment of adenosine of
      nucleoside transport in the rabbit heart, in vivo.

PMID- 9546642
TI  - Ischemic preconditioning in rat heart: no correlation between glycogen content
      and return of function.
AB  - We tested the hypothesis that glycogen levels at the beginning of ischemia affect
      lactate production during ischemia and postischemic contractile function.
      Isolated working rat hearts were perfused at physiological workload with
      bicarbonate buffer containing glucose (10 mmol/L). Hearts were subjected to four
      different preconditioning protocols, and cardiac function was assessed on
      reperfusion. Ischemic preconditioning was induced by either one cycle of 5 min
      ischemia followed by 5, 10, or 20 min of reperfusion (PC5/5, PC5/10, PC5/20), or
      three cycles of 5 min ischemia followed by 5 min of reperfusion (PC3 x 5/5). All
      hearts were subjected to 15 min total, global ischemia, followed by 30 min of
      reperfusion. We measured lactate release, timed the return of aortic flow,
      compared postischemic to preischemic power, and determined tissue metabolites at
      selected time points. Compared with preischemic function, cardiac power during
      reperfusion improved in groups PC5/10 and PC5/20, but was not different from
      control in groups PC5/5 and PC3 x 5/5. There was no correlation between
      preischemic glycogen levels and recovery of function during reperfusion. There
      was also no correlation between glycogen breakdown (or resynthesis) and recovery
      of function. Lactate accumulation during ischemia was lowest in group PC5/20 and
      highest in the group with three cycles of preconditioning (PC3 x 5/5). Lactate
      release during reperfusion was significantly higher in the groups with low
      recovery of power than in the groups with high recovery of power. In glucose
      perfused rat heart recovery of function is independent from both pre- and
      postischemic myocardial glycogen content over a wide range of glycogen levels.
      The ability to utilize lactate during reperfusion is an indicator for
      postischemic return of contractile function.

PMID- 9546644
TI  - Human myocardial ATP content and in vivo contractile function.
AB  - The study was designed to characterize the relationship between the metabolite
      content of human cardiac muscle and in vivo cardiac function. ATP, total adenine
      nucleotides, and NAD were quantified in human myocardial biopsies using high
      performance liquid chromatography. Right ventricular endomyocardial biopsies were
      obtained from 43 patients with dilated cardiomyopathy, 6 with restrictive
      cardiomyopathy, 10 with normal systolic and diastolic function, and from 24 cold
      preserved human donor hearts. Transmural samples of failing right and left
      ventricular free walls were obtained during cardiac transplantation surgery in 8
      patients. ATP, total adenine nucleotides, and NAD were similar in the cold
      preserved donor hearts and in right ventricular endomyocardial biopsies from the
      10 individuals with normal systolic and diastolic function. In contrast, these
      values were significantly depressed in tissue samples from patients with dilated
      or restrictive cardiomyopathy. There was a significant correlation between ATP
      and pulmonary capillary wedge pressures but not ejection fractions. Declines in
      the sizes of myocardial ATP, adenine nucleotide, and pyridine nucleotide pools in
      the human myocardium are associated primarily with diastolic but not systolic
      dysfunction.

PMID- 9546643
TI  - The liver isoform of carnitine palmitoyltransferase I is activated in neonatal
      rat cardiac myocytes by hypoxia.
AB  - Fatty acids are the preferred substrate of ischemic, reperfused myocardium and
      may account for the decreased cardiac efficiency during aerobic recovery.
      Neonatal cardiac myocytes in culture respond to hypoxia/serum- and glucose-free
      medium by a slow decline in ATP which reverses upon oxygenation. This model was
      employed to examine whether carnitine palmitoyltransferase I (CPT-I) modulates
      high rates of beta-oxidation following oxygen deprivation. After 5 h of hypoxia,
      ATP levels decline to 30% control values and CPT-I activity is significantly
      stimulated in hypoxic myocytes with no alteration in cellular carnitine content
      or in the release of the mitochondrial matrix marker, citrate synthase. This
      stimulation was attributed to an increase in the affinity of hypoxic CPT-I for
      carnitine, suggesting that the liver CPT-I isoform is more dominant following
      hypoxia. However, there was no alteration in hypoxic CPT-I inhibition by malonyl
      CoA. DNP-etomoxiryl-CoA, a specific inhibitor of the liver CPT-I isoform,
      uncovered identical Michaelis kinetics of the muscle isoform in control and
      hypoxic myocytes with activation of the liver isoform. Northern blotting did not
      reveal any change in the relative abundance of mRNA for the liver vs. the muscle
      CPT-I isoforms. The tyrosine phosphatase inhibitor, pervanadate, reversed the
      hypoxia-induced activation of CPT-I and returned the affinity of cardiac CPT-I
      for carnitine to control. Reoxygenation was also associated with a return of CPT
      I activity to control levels. The data demonstrate that CPT-I is activated upon
      ATP depletion. Lower enzyme activities are present in control and reoxygenated
      cells where ATP is abundant or when phosphatases are inhibited. This is the first
      suggestion that phosphorylation may modulate the activity of the liver CPT-I
      isoform in heart.

PMID- 9546645
TI  - Differential cardioprotection with selective inhibitors of adenosine metabolism
      and transport: role of purine release in ischemic and reperfusion injury.
AB  - In a previous report, we have demonstrated that simultaneous inhibition of
      nucleoside transport and adenosine deaminase accumulates endogenous adenosine and
      protects the myocardium against stunning. The differential cardioprotective
      effects of erythro-9(2-hydroxy-3-nonyl)-adenine (EHNA), a potent inhibitor of
      adenosine deamination but not transport, and p-nitrobenzylthioinosine (NBMPR), a
      selective blocker of adenosine and inosine transport, are not known. Thirty-seven
      anaesthetized adult dogs were instrumented to monitor left ventricular
      performance using sonomicrometery. Dogs were randomly assigned into four groups.
      The control group (n = 8) received only the vehicle solution. Treated groups
      received saline containing 100 microM EHNA (EHNA-group, n = 7), 25 microM NBMPR
      (NBMPR-group, n = 7), or a combination of 100 microM EHNA and 25 microM NBMPR
      (EHNA/NBMPR-group, n = 10). Hearts were subjected to 30 min of normothermic
      global ischaemia and 60 min of reperfusion while on bypass. Adenine nucleotides,
      nucleosides, oxypurines and NAD+ were determined in extracts of transmural
      myocardial biopsies using HPLC. TTC staining revealed the absence of necrosis in
      this model. Drug administration did not affect myocardial ATP metabolism and
      cardiac function in the normal myocardium. Ischemia caused about 50% ATP
      depletion and accumulation of nucleosides. The ratio between adenosine/inosine at
      the end of ischemia was 1:10, 1:1, 1:1 and 10:1 in the control, EHNA-, NBMPR- and
      EHNA/NBMPR-group, respectively. Upon reperfusion, both nucleosides washed out
      from the myocardium in the control and EHNA-group while retained in the
      myocardium in the NBMPR and EHNA/NBMPR groups. Ventricular dysfunction 'stunning'
      persisted in the control group (52%) and in the EHNA-treated group (32%) after 30
      min of reperfusion. Significant improvement of function was observed in the EHNA
      group only after 60 min of reperfusion. LV function recovered in the NBMPR- and
      EHNA/NBMPR-treated groups during reperfusion. ATP recovery occurred only when
      animals were pretreated with the combination of EHNA/NBMPR and remained depressed
      in the control group and EHNA and NBMPR-treated groups. At post mortem, TTC
      staining revealed the absence of myocardial necrosis. Superior myocardial
      protection was observed with inhibition of nucleoside transport by NBMPR alone or
      in combination with inhibition of adenosine deaminase by EHNA. Selective blockade
      of nucleoside transport by NBMPR is more cardioprotective than inhibition of
      adenosine deaminase alone in attenuating myocardial stunning. It is not known why
      EHNA partially inhibit adenosine deaminase, in vivo.

PMID- 9546646
TI  - Effects of nucleoside transport inhibitors and adenine/ribose supply on ATP
      concentration and adenosine production in cardiac myocytes.
AB  - Adenosine plays an important role in protection of the heart before, during and
      after ischemia. Nucleoside transport inhibitors (NTI) increase adenosine
      concentration without inducing ischemia by preventing its uptake and metabolism
      in cardiac cells. However, prolonged effects of nucleoside transport inhibitors
      on adenosine and nucleotide metabolism and its combined effect with nucleotide
      precursors has not been established in cardiomyocytes. The aim of this study was
      to investigate the effect of two nucleoside transport inhibitors, dipyridamole
      (DIPY) and nitrobenzylthioinosine (NBTI) alone or combined with adenine and
      ribose on adenosine production and ATP content in cardiomyocytes. Rat
      cardiomyocytes were isolated using collagenase perfusion technique. Isolated cell
      suspensions were incubated for up to 480 min with different substrates and
      inhibitors as follows: (1) control; (2) 100 microM adenine and 2.5 mM ribose; (3)
      10 microM DIPY; (4) 1 microM NBTI; (5) DIPY, adenine and ribose and (6) NBTI,
      adenine and ribose. Five microM EHNA (erythro-9(2-hydroxy-3-nonyl)adenine, an
      inhibitor of adenosine deaminase) was added to all incubations. After incubation,
      extracts of myocyte suspension were analysed by HPLC for adenine nucleotides and
      metabolite concentrations. ATP content decreased in cardiomyocytes after 8 h of
      incubation with DIPY, while no change was observed with NBTI or without
      inhibitors. Adenosine concentration increased with both DIPY and NBTI. In the
      presence of adenine and ribose an elevation in ATP concentration was observed,
      but no significant change in adenosine content. In the presence of DIPY or NBTI
      together with adenine and ribose, an enhancement in cardiomyocyte ATP
      concentration was observed together with an increase in adenosine content. This
      increase in adenosine production was especially prominent with DIPY. In
      conclusion, dipyridamole causes a decrease in ATP concentration in isolated
      cardiomyocytes by mechanisms other than nucleoside transport inhibition. Addition
      of adenine/ribose with dipyridamole prevents the depletion of ATP. Combination of
      adenine/ribose with nucleoside transport inhibitors may also further enhance
      adenosine concentration and thus, could be more effective as pharmacological
      agents for treatment.

PMID- 9546647
TI  - Inter-alpha-trypsin inhibitor proteoglycan family--a group of proteins binding
      and stabilizing the extracellular matrix.
AB  - Extracellular matrix (ECM) is composed of several macromolecules associated in a
      complex network. This structure allows cells to adhere, migrate and interact.
      Hyaluronic acid (HA) is a glycosaminoglycan (GAG) and a major representative of
      ECM. HA-binding proteins such as CD44, aggrecan, and versican, have been
      implicated in structuring the ECM by stabilizing large macromolecular aggregates.
      They also play an important role in tumor metastasis and cell motility. Recently,
      further HA-binding proteins were identified: the inter-alpha-trypsin
      inhibitor(ITI)-related proteins. ITI is a glycoprotein composed of three
      polypeptides: two heavy chains (HC1 and HC2) and one light chain (bikunin).
      Bikunin confers the protease-inhibitor function. The heavy chains' function was
      unknown. Recent studies have shown that HC1 and HC2 are linked in vivo and in
      vitro to hyaluronic acid. This linkage greatly improves extracellular matrix
      stability. It also demonstrates that ITI-related proteins might be considered as
      HA-binding proteins (HABP). The ITI related proteins are composed of four
      polypeptides (HC1, HC2, HC3 and the bikunin) encoded by four genes H1, H2, H3 and
      L. Unlike the majority of plasma protein a non-disulfide covalent linkage exists
      between heavy chains and bikunin. This review presents the recent progress
      concerning the interactions between ITI and ECM showing that ITI-related proteins
      are HABP members. We will focus on the heavy chain linkage with HA, which
      represents the demonstration of covalent binding between proteins and HA.

PMID- 9546648
TI  - Evaluation of the impact of S-adenosylhomocysteine metabolic pools on cytosine
      methylation of the tobacco genome.
AB  - We explored the possibility that the cytosine DNA methylation might be regulated
      by S-adenosyl-L-methionine (AdoMet) and S-adenosyl-L-homocysteine (AdoHcy) pools
      in plant cells. In order to change the AdoHcy/AdoMet ratio (methylation index),
      (S)-9-(2,3-dihydroxypropyl)adenine was employed, a selective reversible inhibitor
      of cellular S-adenosyl-L-homocysteine hydrolase. Micromolar concentrations of the
      inhibitor increased dramatically (more than 1000-fold) intracellular AdoHcy
      levels (and concominantly the AdoHcy/AdoMet ratio) in tobacco TBY-2 cells. No
      toxic effect of the drug was observed and the cells displayed only marginal
      inhibition of growth at high AdoHcy levels. At near equal intracellular
      concentrations of AdoHcy and AdoMet, a significant reduction of cytosine
      methylation in transcribed (5SrDNA) and non-transcribed (HRS60, NTRS) sequences
      was observed. Interestingly, the CpCpG and CpApG trinucleotide targets appeared
      to be most sensitive to changes in the methylation index. Methylation of cytosine
      residues at CpG sites was not affected even at AdoHcy/AdoMet ratio of > 10. These
      results support the possible regulation of DNA methylation via AdoHcy/AdoMet
      metabolic pathways in plant cells.

PMID- 9546649
TI  - Occurrence of two plastidic ATP/ADP transporters in Arabidopsis thaliana L.-
      molecular characterisation and comparative structural analysis of similar ATP/ADP
      translocators from plastids and Rickettsia prowazekii.
AB  - Recently, we sequenced a cDNA clone from Arabidopsis thaliana L. encoding an
      ATP/ADP transporter protein (AATP1) located in the plastid envelope membrane. The
      deduced amino acid sequence of AATP1 exhibits a high degree of similarity (> 66%)
      to the ATP/ADP transporter from the obligate intracellular gram-negative
      bacterium Rickettsia prowazekii. Here we report a second plastidic ATP/ADP
      carrier from A. thaliana (AATP2). As deduced from the amino acid sequence, AATP2
      exhibits 77.6% identity to AATP1 and 36% to the rickettsial protein. Hydropathy
      analysis indicates that all three translocators are highly hydrophobic membrane
      proteins, which exhibit marked similarities and differences. The AATP1
      translocator lacks the sixth transmembrane domain that is present in AATP2 and
      the bacterial transporter in R. prowazekii. In contrast to AATP1 and the
      bacterial transport protein, only AATP2 exhibits a truncated C-terminal end. To
      compare the general biochemical properties of AATP2 with the known transport
      properties of AATP1 we cloned the entire AATP2 cDNA into plasmid pJT118, leading
      to the presence of an additional N-terminal histidine tag of 10 amino acids. For
      heterologous expression of His10-AATP2 we chose the Escherichia coli strain C43,
      which was reported recently to allow overproduction of eucaryotic membrane
      transport proteins. After transformation and subsequent induction by
      isopropylthio-2-D-galactopyranoside intact E. coli cells harbouring plasmid
      pJT118 showed import of radioactively labelled ATP and ADP. As deduced from a
      Lineweaver-Burk analysis His10-AATP2 exhibited apparent Km values for ATP and ADP
      of 22 microM and 20 microM, respectively. Import of ADP into His10-AATP2
      expressing E. coli cells occurred at a rate of 24 nmol x mg protein(-1) x h(-1),
      which was about threefold faster than import of ATP. These biochemical
      characteristics are similar to transport properties of the heterologously
      expressed His10-AATP1 protein.

PMID- 9546651
TI  - In vitro characterisation of the interaction between newly synthesised proteins
      and a pancreatic isoform of protein disulphide isomerase.
AB  - The lumen of the endoplasmic reticulum (ER) contains an array of molecular
      chaperones and folding factors that modulate the folding and assembly of newly
      synthesised proteins entering the secretory pathway. One of these components,
      protein disulphide isomerase (PDI), facilitates the formation of the correct
      disulphide bonds within newly synthesised polypeptides, and is the archetype for
      a family of sequence related PDI-like proteins. We have investigated the
      interaction between a recently identified, pancreas-specific PDI-like protein
      (PDIp), and in vitro synthesised secretory and membrane proteins produced in the
      presence of ER-derived canine pancreatic microsomes. We have previously
      established that a second PDI-like protein, ERp57, interacts specifically with N
      glycosylated proteins. In contrast, we find that the interaction of PDIp with
      newly synthesised proteins occurs independently of any requirement for N-linked
      glycosylation. In this respect, the properties of PDIp mirror those of archetypal
      PDI. When the carbohydrate-dependent interactions between glycoproteins and ERp57
      are blocked by drug treatment, the association of these precursors with both PDIp
      and PDI is enhanced. We propose that PDI-like proteins have overlapping
      specificity and may exhibit some degree of functional redundancy.

PMID- 9546650
TI  - Effect of reversible reactions on isotope label redistribution--analysis of the
      pentose phosphate pathway.
AB  - The pentose phosphate pathway plays several key roles in metabolism including
      supply of biosynthetic carbon skeletons and reducing power. Previous research has
      focused on determining the fluxes through the reactions of this pathway using
      carbon-labeled substrates and models that make certain assumptions about the
      reversibility of the transketolase and transaldolase reactions in the
      nonoxidative pathway. These assumptions, however, have resulted in
      inconsistencies between the predicted carbon label distributions using these
      models and those determined experimentally. A general metabolic reaction network
      model developed in this paper and applied to the pentose phosphate pathway not
      only incorporates reaction reversibility but also accounts for the effect of
      individually varying extents of reaction reversibility on labeled carbon
      fractional enrichment values for intermediate metabolites. In addition, an
      algorithm is presented that can be used to calculate the three individual
      transaldolase and transketolase extents of reversibility. The results of this
      method show that varying extents of reaction reversibility have an observable
      effect on the metabolite carbon label distributions which can in turn affect flux
      calculation for other parts of the metabolic network such as the tricarboxylic
      acid cycle. In addition, the observability of reversibility extent and accuracy
      of flux calculations depend on the particular choice of metabolite carbon
      enrichments measured. In particular, [6-13C]hexose 6-phosphate and [4
      13C]erythrose 4-phosphate carbon enrichment values resulting from [1-13C]glucose
      feeding contained more information as compared to those from ribose 5-phosphate.
      This analysis was applied to literature data of metabolite carbon labeling that
      resulted from supplying either 13C- or 14C-enriched substrates to several cell
      types growing under various conditions. The specific activities of metabolite
      carbon atoms taken from rat epididymal adipose tissue, goosefish islet cells,
      Corynebacterium glutamicum, and Escherichia coli supplied with either [2
      14C]glucose or [1-13C]glucose demonstrate how reversibility is present in the
      pentose phosphate pathway and the extents of reversibility can be estimated from
      labeled carbon data sets.

PMID- 9546652
TI  - Atherogenic concentrations of native low-density lipoproteins down-regulate
      nitric-oxide-synthase mRNA and protein levels in endothelial cells.
AB  - The nitric oxide synthase family of proteins is the unique class of mammalian
      enzymes that metabolizes L-arginine to form nitric oxide (NO). The atherogenic
      action of low-density lipoproteins (LDL) may be mediated, in part, by its effects
      on endothelial-derived nitric oxide. To determine whether native LDL (nLDL), at
      atherogenic concentrations, are capable of modulating NO synthase expression, we
      treated human umbilical vein endothelial cells with increasing concentrations of
      human nLDL (0-240 mg cholesterol/dl) for various time periods (2-48 h). Northern
      and western blot analyses indicate that both endothelial NO-synthase mRNA and
      protein are down-regulated by atherogenic concentrations of nLDL (180 and 240 mg
      cholesterol/dl) after 48 h of incubation. Cycloheximide and actinomycin D
      experiments suggest that this down-regulation operates at a transcriptional
      level. Additionally, treatment of the cells with high-density lipoproteins, at
      human physiological concentrations (45 mg cholesterol/dl), does not appear to
      alter the expression of endothelial NO synthase which seems to indicate that nLDL
      affect the gene transcription rate by a specific and concentration-dependent
      mechanism. These findings may have important implications because they provide a
      novel mechanism by which hypercholesterolemia induces early changes on
      endothelial cells that could have pathophysiological significance in the
      atherosclerotic process.

PMID- 9546653
TI  - Detection of abscisic-acid-binding proteins in the microsomal protein fraction of
      Arabidopsis thaliana with abscisic-acid-protein conjugates used as affinity
      probes.
AB  - A family of affinity probes has been generated to detect and purify abscisic-acid
      (ABA)-binding proteins, by coupling ABA onto carrier proteins (ovalbumin or BSA)
      through the C1 carboxyl group or the C4' carbonyl group of ABA. ELISA detection
      showed that these ABA-protein conjugates bound efficiently to the solubilized
      microsomal protein fraction of Arabidopsis thaliana, but not to the soluble
      protein fraction. Heat or proteolytic treatments inhibited the binding of the
      conjugates, indicating the protein nature of these binding sites. After membrane
      purification of the microsomes, the binding sites were found to be preferentially
      located in the plasma membrane fraction. The binding of the conjugates was
      independent of the nature of the carrier protein or the ABA-carrier protein
      linker, but was competitively inhibited with an anti-ABA mAb. Furthermore, the
      competitive inhibition of the binding of the conjugates with ABA, but not with
      the inactive ABA methyl ester analog, demonstrated the specificity of the binding
      and the saturability of the binding sites. The binding of the conjugates was
      strictly correlated to the ABA/carrier protein molar coupling ratio, confirming
      that the affinity of the conjugates to the ABA-binding proteins was enhanced by
      the increase in the probability of binding events. The experimental approach
      permits a new insight into the nature of membrane-associated ABA-binding
      proteins.

PMID- 9546654
TI  - Functional expression of recombinant N-methyl-D-aspartate receptors in the yeast
      Saccharomyces cerevisiae--localization and pharmacological characterization.
AB  - The yeast Saccharomyces cerevisiae was used for expressing the genes encoding the
      ionotropic N-methyl-D-aspartate (NMDA) receptor subunits from rats (NR1a, NR2A,
      NR2C) and mice (NR2B). Four plasmids were constructed by cloning the different
      NMDA receptor genes in the two multi-copy yeast-Escherichia coli shuttle vectors
      pMB01 (--> NR1a gene) and pMB02 (--> NR2A-2C genes). The protease-deficient S.
      cerevisiae strain cI3-ABYS-86 (leu-, ura-) was transformed or co-transformed with
      the resulting plasmids pMBNR1a (leu+) or pMBNR1a/pMBNR2A-C (ura+) respectively.
      Western blotting analysis with antibodies raised against amino acid sequences at
      the C-termini of the respective subunits revealed that the recombinant receptor
      proteins were differently expressed and only partially glycosylated in the cell
      membranes of the recombinant yeast strains. The expression and localization of
      the recombinant NMDA receptor proteins were also proved by immunofluorescence
      microscopy which indicated a distinct expression of the different NMDA receptor
      subunits in the plasma membrane of the transformed yeast cells. Pharmacological
      characterization of crude membrane preparations of the recombinant yeast cells
      showed saturable binding of the glycine antagonist [3H]MDL105,519 with Kd values
      of 56.9 +/- 6.19 nM (NR1a/NR2A), 26.72 +/- 2.13 nM (NR1a/NR2B), and 21.22 +/-
      1.64 nM (NR1a/NR2C), and bound capacities of 17.94 +/- 1.24 pmol/mg membrane
      protein (NR1a/NR2A), 11.45 +/- 0.67 pmol/mg (NR1a/NR2B), and 16.15 +/- 0.86
      (NR1a/NR2C) pmol/mg. The [3H]MDL105,519 binding was inhibited by the glycine
      antagonist 5,7-dichlorokynurenate, ethyl-2-carboxy-4,6-dichloro-3-indoleacetate,
      and itself, but not by glycine, D-serine or 1-amino-cyclopropanecarboxylic acid.
      Specific binding of [3H]glycine or the NMDA channel blocker [3H]dizolcipine were
      not observed.

PMID- 9546655
TI  - Galectin-1 from ovine placenta--amino-acid sequence, physicochemical properties
      and implications in T-cell death.
AB  - In the present study we report the amino-acid sequence, carbohydrate specificity
      and overall biochemical and physicochemical properties of galectin-1, a beta
      galactoside-binding lectin from ovine placenta. The complete amino-acid sequence,
      obtained by tryptic and chymotryptic digestion, revealed that this carbohydrate
      binding protein shares all the absolutely preserved and critical residues found
      in other members of the mammalian galectin-1 subfamily. Moreover, conformational
      changes induced by protein interaction with its specific disaccharide were
      investigated by fourth-derivative spectral analysis, intrinsic tryptophan
      fluorescence measurements and circular dichroism. The first two methods indicated
      changes in the environment of aromatic residues, in agreement with the role of
      Trp in carbohydrate binding. The quenching of the fluorescence emission upon
      addition of lactose, allowed us to calculate the Kd for its interaction with the
      galectin, which was 0.157 +/- 0.02 mM. The far-ultraviolet CD spectra is
      consistent with the large extent of beta-sheet structure described for other
      galectins. Addition of lactose produced no significant changes, suggesting that
      it causes no modifications in the secondary structure of the lectin. In addition,
      we explored its potential cell-growth inhibitory activity and implications in T
      cell death. Finally, we also provide evidence showing that antagonic properties
      of galectins-1 and -3 are reciprocally neutralized in a natural mixture of both
      proteins, suggesting that they could play an important role in the regulation of
      cell proliferation and death, according to physiological requirements at
      particular developmental stages of the placenta, thus allowing successful
      pregnancy to occur.

PMID- 9546656
TI  - Oligomeric structure of the repressor of the bacteriophage Mu early operon.
AB  - The regulation of the lytic and lysogenic development in the life cycle of
      bacteriophage Mu is regulated in part by its repressor, c, which binds to three
      operator sites, O1, O2 and O3, overlapping two divergent promoters. The
      oligomeric structure of this repressor protein was investigated by hydrodynamic
      and biochemical methods. Size-exclusion chromatography, analytical
      ultracentrifugation, dynamic light scattering, crosslinking and direct electron
      microscopy observations suggest that c exists primarily as a hexamer with a
      molecular mass of 120-140 kDa at low concentrations, i.e. in the 10-microM range.
      This molecule undergoes a self-assembly process leading to dodecamers and higher
      order species as the concentration is further increased in a manner depending on
      the nature of the solvent. Our results also suggest that these species have an
      elongated structure, and a possible arrangement of the subunits within the
      hexamer is proposed. The implication of this unusual quaternary structure for a
      repressor in its interaction with the operator sites O1 and O2 remains to be
      elucidated.

PMID- 9546657
TI  - Conformer selection and differential restriction of ligand mobility by a plant
      lectin--conformational behaviour of Galbeta1-3GlcNAcbeta1-R, Galbeta1
      3GalNAcbeta1-R and Galbeta1-2Galbeta1-R' in the free state and complexed with
      galactoside-specific mistletoe lectin as revealed by random-walk and
      conformational-clustering molecular-mechanics.
AB  - To study conformational parameters of ligands before and after complex formation
      with the galactoside-binding agglutinin of Viscum album L. (VAA) in solution,
      combined computer-assisted random walk molecular mechanics (RAMM) calculations
      extended by conformational clustering analysis (CCA), molecular dynamics (MD)
      simulations as well as two-dimensional rotating-frame nuclear Overhauser effect
      (ROE) and two-dimensional nuclear Overhauser effect (NOE) spectroscopy NMR
      experiments were employed. Derivatives of the naturally occurring disaccharides
      Galbeta1-3GlcNAcbeta1-R and Galbeta1-3GalNAcbeta1-R as well as of a synthetic
      high-affinity binding partner, i.e. the disaccharide Galbeta1-2Galbeta1-R', were
      chosen as ligands in this study. The disaccharides displayed inherent flexibility
      in the valley of the global minimum between phi/psi combinations of (40
      degrees/60 degrees) and (40 degrees/-60 degrees). Calculations of the de-N
      acetylated sugars revealed that presence of this group did not markedly influence
      the distribution of low-energy conformers in the phi, psi, epsilon plot.
      Occupation of side minima at phi/psi (180 degrees/0 degrees) or (0 degrees/180
      degrees) is either unlikely or low according to the results of MD simulations and
      RAMM calculations extended by CCA. Notably, these side minima define
      conformations which are not stable during a MD simulation. Transitions to other
      minima occur already a few picoseconds after the start of the simulation. NMR
      experiments of the free-state ligand confirmed the validity of the data sets
      obtained by the calculations. Following the description of the conformational
      space in the free-state NMR experiments were performed for these disaccharides
      complexed with VAA. They yielded two interresidual contacts for Galbeta1
      3GlcNAcbeta1-R and Galbeta1-2Galbeta1-R'. The ligand conformations in the complex
      did not deviate markedly from those of a minimum conformation in the free state.
      One- and two-dimensional transferred nuclear Overhauser enhancement (TRNOE)
      experiments at different mixing times excluded the influence of spin-diffusion
      effects. When the NOE build-up curves in the three studied cases were compared,
      the residual mobility of the penultimate carbohydrate unit of Galbeta1
      3GalNAcbeta1-R was observed to be higher than that of the respective hexopyranose
      unit of the other two bound ligands. Due to the availability of the
      conformational parameters of Galbeta1-2Galbeta1-R' in association with a
      galectin, namely the beta-galactoside-binding protein from chicken liver, it is
      remarkable to note that this ligand displays different conformations in the
      binding sites of either the plant or the animal lectin. They correspond to local
      energy-minimum conformations in the phi,psi, epsilon plot and substantiate
      differential conformer selection by these two lectins with identical nominal
      monosaccharide specificity.

PMID- 9546658
TI  - Conformation of desmopressin, an analogue of the peptide hormone vasopressin, in
      aqueous solution as determined by NMR spectroscopy.
AB  - Desmopressin (1-desamino-[DArg8]vasopressin, is a synthetic analogue of the
      neurohypophyseal peptide hormone vasopressin which has high antidiuretic and
      antibleeding potency. The structure of desmopressin has been determined in
      aqueous solution by two-dimensional NMR techniques and molecular dynamics
      simulations. Both standard and time-averaged distance restraints were used in
      structure calculations because of the inherent flexibility in small peptides. 21
      models calculated with standard restraints were compared with structures refined
      with time-averaged distance restraints and were found to be good representatives
      of the conformational ensemble of desmopressin. The macrocyclic ring forms an
      inverse gamma-turn centered around Gln4. Residues 1 and 2, the disulphide bridge
      and the three-residue acyclic tail were found to be flexible in solution.
      Residues 4-6 in the ensemble of calculated structures contain essentially the
      same backbone conformation as in the crystal structure of pressinoic acid, the
      cyclic moiety of vasopressin, whereas residues 2-6 superimpose on the NMR-derived
      conformation of oxytocin bound to neurophysin. The results presented in this work
      suggest that, in addition to the differences in sequence between desmopressin and
      vasopressin, differences in conformational and dynamic properties between the two
      compounds explain their pharmacological differences.

PMID- 9546659
TI  - The V3 loop of human immunodeficiency virus type-1 envelope protein is a high
      affinity ligand for immunophilins present in human blood.
AB  - Human immunodeficiency virus type-1 (HIV-1) infection requires binding of the
      envelope protein gp120 to host CD4 receptors and the action of the chemokine
      receptors CXCR4 or CCR5, which define cell tropism. The proline-containing V3
      loop of gp120 determines the selection of the chemokine receptor and participates
      in conformational changes on binding of gp120 to CD4. In this study, we show that
      macrophage-tropic and T-cell-tropic V3 loop peptides bind specifically to the
      active site of the immunophilins FK506-binding protein (FKBP12), and cyclophilins
      A and B. Macrophage-tropic and T-cell-tropic V3 loop peptides inhibited the
      peptidyl-prolyl cis-trans isomerase (PPIase) activities of the immunophilins. Kd
      values in the range 0.036-4.1 microM were determined with V3 loop peptides
      labeled with an environmentally sensitive fluorophore. The observed binding
      properties of the V3 loop peptides reveal structural motifs of linear water
      soluble peptidic substrates for tight interaction with immunophilins. FKBP12, and
      cyclophilins A and B were found to be present in normal human blood in the ranges
      0.8-1.7, 1.4-2.3 and 2.4-3.1 nM, respectively, as demonstrated by PPIase activity
      measurements and western blot analysis. Cyclophilins A and B levels in serum of
      HIV-1-infected individuals were increased 3.6-fold and 1.6-fold. Due to the
      interaction of immunophilins with V3 loop peptides and with the envelope protein
      gp120, a role of immunophilins in HIV pathogenesis as conformases or docking
      mediators seems possible, since immunophilin receptors on cell membranes and
      immunophilin-related virulence factors of pathogens have been identified.

PMID- 9546660
TI  - Comparative study of the catalytic domain of phosphorylating glyceraldehyde-3
      phosphate dehydrogenases from bacteria and archaea via essential cysteine probes
      and site-directed mutagenesis.
AB  - Phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GraP-DH) catalyzes the
      oxidative phosphorylation of D-glyceraldehyde-3-phosphate to form 1.3
      diphosphoglycerate. The currently accepted mechanism involves an oxidoreduction
      step followed by a phosphorylation. Two essential aminoacids, Cys149 and His176
      are involved in the chemical mechanism of bacterial and eukaryotic GraP-DHs.
      Roles have been assigned to the His176 as (a) a chemical activator for enhancing
      the reactivity of Cys149, (b) a stabilizator of the tetrahedral transition
      states, and (c) a base catalyst facilitating hydride transfer towards NAD. In a
      previous study carried out on Escherichia coli GraP-DH [Soukri, A., Mougin, A.,
      Corbier, C., Wonacott, A. J., Branlant, C. & Branlant, G. (1989) Biochemistry,
      28, 2586-2592], the role of His176 as an activator of the reactivity of Cys149
      was studied. Here, we further investigated the role of the His residue in the
      chemical mechanism of phosphorylating GraP-DH from E. coli and Bacillus
      stearothermophilus. The chemical reactivity of Cys149 in the His176Asn mutant was
      reinvestigated. At neutral pH, its reactivity was shown to be at least as high as
      that observed in the Cys-/His+ ion pair present in the wild type. No pre-steady
      state burst of NADH was found with the His176Asn mutant in contrast to what is
      observed for the wild type, and a primary isotope effect was observed when D-[1
      2H]glyceraldehyde-3-phosphate was used as the substrate. Therefore, the major
      role of the His176 in the catalytic mechanism under physiological conditions is
      not to activate the nucleophilicity of Cys149 but first to facilitate the hydride
      transfer. These results hypothesized that a phosphorylating GraP-DH possessing a
      different protein environment competent to increase the nucleophilic character of
      the essential Cys residue and to favor the hydride transfer in place of His,
      could be enzymically efficient. This is most likely the case for archaeal
      Methanothermus fervidus GraP-DH which shares less than 15% amino-acid identity
      with the bacterial or eukaryotic counterparts. No Cys-/His+ ion pair was
      detectable. Only one thiolate entity was observed with an apparent pKa of 6.2.
      This result was confirmed by the fact that none of the mutations of the five
      invariant His changed the catalytic efficiency.

PMID- 9546661
TI  - Conferring aldosterone synthesis to human CYP11B1 by replacing key amino acid
      residues with CYP11B2-specific ones.
AB  - Performing residue-swapping experiments between the highly conserved human
      steroidogenic proteins CYP11B1 and CYP11B2 we recently demonstrated that
      replacement of specific residues at position 301, 302 and 320 in the aldosterone
      producing CYP11B2 protein for such residues that were specific for the highly
      similar cortisol-producing CYP11B1 protein elevated the 11beta-hydroxylase
      activity dramatically. Conversely, aldosterone synthesis in the triple mutant was
      severely impaired. Here we provide evidence that in a reciprocal experiment,
      CYP11B2-specific amino acids at position 320 and 335 endowed CYP11B1 with an 18
      oxidase function amounting to 20% of the CYP11B2 wild-type activity, thus
      changing the specificity of steroid hydroxylation by only one point mutation.
      Combining substitutions at positions 296, 301, 302, 320, 335 and 339 did,
      however, not result in further enhancement. Paradoxically, 11beta-hydroxylation
      was not or only marginally affected in CYP11B1 mutants, indicating an alternative
      structural basis for this activity in CYP11B1 compared with the engineered
      CYP11B2 variant. Our results suggest that the sequence spanned by amino acids 301
      and 335 constitutes part of the substrate-binding site in CYP11B1 and CYP11B2 as
      well. By constructing chimeric proteins we further investigated the effect of the
      C-terminal portions of both proteins and found that diverging residues at
      positions 471, 472, 492, 493 and 494 were insignificant for the stereospecificity
      and regiospecificity of steroid hydroxylation.

PMID- 9546662
TI  - An Escherichia coli hydrogenase-3-type hydrogenase in methanogenic archaea.
AB  - Methanogenic archaea are known to contain two types of [NiFe] hydrogenases
      designated F420-reducing hydrogenase and F420-non-reducing hydrogenase. We report
      here that they additionally contain Escherichia coli hydrogenase-3-type [NiFe]
      hydrogenases. The evidence is based on biochemical studies and analysis of the
      subunit primary structure of this hydrogenase (designated Ech) purified from
      membranes of acetate-grown cells of Methanosarcina barkeri. The subunits EchE and
      EchC of the EchABCDEF complex showed 34% and 45% sequence identity to the nickel
      containing large subunit HycE and to the iron-sulfur cluster containing small
      subunit HycG, respectively, of the hydrogenase in the formate hydrogen lyase
      complex from E. coli. Analysis of the totally sequenced genomes of Methanococcus
      jannaschii and Methanobacterium thermoautotrophicum strain deltaH revealed that
      these organisms contain similar open reading frames, indicating the presence of
      an E. coli hydrogenase-3-type hydrogenase also in these methanogenic archaea.

PMID- 9546663
TI  - Fatty acid elongation in yeast--biochemical characteristics of the enzyme system
      and isolation of elongation-defective mutants.
AB  - Elongation of long-chain fatty acids was investigated in yeast mutants lacking
      endogenous de novo fatty acid synthesis. In this background, in vitro fatty acid
      elongation was dependent strictly on the substrates malonyl-CoA, NADPH and a
      medium-chain or long-chain acyl-CoA primer of 10 or more carbon atoms. Maximal
      activity was observed with primers containing 12-14 carbon atoms, while shorter
      chain-length acyl-CoA were almost (octanoyl-CoA) or completely (hexanoyl-CoA,
      acetyl-CoA) inactive. In particular, acetyl-CoA was inactive as a primer and as
      extender unit. The Michaelis constants for octanoyl-CoA (0.33 mM), decanoyl-CoA
      (0.83 mM) lauroyl-CoA (0.05 mM), myristoyl-CoA (0.4 mM) and palmitoyl-CoA (0.13
      mM) were determined and were comparable for fatty acid synthesis and elongation.
      In contrast, the affinity of malonyl-CoA was 17-fold lower for elongation (Km =
      0.13 mM) than for the fatty acid synthase (FAS) system. With increasing chain
      length of the primer (> or = 12:0), fatty acid elongation becomes increasingly
      sensitive to substrate inhibition. Due to the activation of endogenous fatty
      acids, ATP exhibits a stimulatory effect at suboptimal but not at saturating
      substrate concentrations. In the yeast cell homogenate, the specific activity of
      fatty acid elongation is about 10-20-fold lower than that of de novo fatty acid
      synthesis. The same elongation activity is observed in respiratory competent and
      in mitochondrially defective cells. The products of in vitro fatty acid
      elongation are fatty acids of 15-17 or 22-26 carbon atoms, depending on whether
      tridecanoyl-CoA or stearoyl-CoA is used as a primer. In vitro, the elongation
      products are converted in part, by alpha-oxidation, to their odd-chain-length
      lower homologues or are hydrolyzed to fatty acids. In contrast, no odd-chain
      length elongation products or very-long-chain fatty acids (VLCFA) shorter than
      26:0 are observed in vivo. Hence, VLCFA synthesis exhibits a higher processivity
      in vivo than in the cell homogenate. In addition, the in vivo process appears to
      be protected against side reactions such as hydrolysis or alpha-oxidation. Yeast
      mutants defective in 12:0 or 13:0 elongation were derived from fas-mutant strains
      according to their failure to grow on 13:0-supplemented media. In vivo, 12:0
      elongation was reduced to 0-10% of the normal level, while 16:0 elongation and
      VLCFA synthesis were unimpaired. It is concluded that yeast contains either two
      different elongation systems, or that the respective mutation interferes
      differentially with medium-chain and long-chain fatty acid elongation. The yeast
      gene affected in the elongation-defective mutants was isolated and, upon
      sequencing, identified as the known ELO1 sequence. It encodes a putative membrane
      protein of 32-kDa molecular mass with no obvious similarity to any of the known
      FAS component enzymes.

PMID- 9546664
TI  - Purification and properties of an extremely thermostable membrane-bound sulfur
      reducing complex from the hyperthermophilic Pyrodictium abyssi.
AB  - The chemolithoautotrophic archaeon Pyrodictium abyssi isolate TAG 11 gains energy
      by reducing sulfur with H2 to H2S. From this hyperthermophile, a sulfur-reducing
      complex catalyzing this reaction was purified 13.5-fold. The native complex
      exhibited a brownish-yellow colour and showed an apparent molecular mass of 520
      kDa. SDS/PAGE revealed the presence of nine different major polypeptides with
      apparent molecular masses of 82, 72, 65, 50, 47, 42, 40, 30 and 24 kDa. The
      native complex contained 50-55 mol acid-labile sulfur, 50-55 mol iron, 1.6 mol
      nickel, 1.2 mol copper, 2.8 mol cytochrome b and 0.3 mol cytochrome c (all per
      mol native complex). The temperature optimum of the H2:sulfur oxidoreductase
      complex was 100 degrees C, which is consistent with the physiological growth
      optimum of the native organism. The complex is extremely heat stable. During 5 h
      incubation at 100 degrees C, no decrease in H2S-forming activity could be
      observed.

PMID- 9546665
TI  - Localization of carbohydrate chains of pig sperm ligand in the glycoprotein ZPB
      of egg zona pellucida.
AB  - The three glycoproteins of pig zona pellucida (ZPA, ZPB and ZPC) can be separated
      into ZPA and a mixture of ZPB/ZPC by gel-filtration HPLC. We have shown
      previously that the neutral complex-type N-linked carbohydrate chains obtained
      from ZPB/ZPC possess sperm-binding activity. Intact ZPB and ZPC cannot be
      separated from each other unless acidic N-acetyllactosamine regions of their
      carbohydrate chains are removed by endo-beta-galactosidase digestion. The endo
      beta-galactosidase-digested ZPB retains the sperm-binding activity. Recently, we
      have reported that N-linked carbohydrate chains of N-terminal fragment (residues
      137-247) obtained from endo-beta-galactosidase-digested ZPB are involved mainly
      in sperm binding [Yonezawa, N., Mitsui, S., Kudo, K. & Nakano, M. (1997) Eur. J.
      Biochem. 248, 86-92]. In this study, we separated the intact neutral N-linked
      chains from the ZPB/ZPC mixture into diantennary chains and triantennary and
      tetraantennary chains by affinity chromatography on Concanavalia ensiformis
      agglutinin. An in vitro competition assay revealed that triantennary and
      tetraantennary chains possess a sperm-binding activity stronger than that of
      diantennary chains. Three glycopeptides, having one Asn residue to which the
      carbohydrate chain is linked, were obtained by lysyl endopeptidase digestion of
      the heat-solubilized zonae containing intact ZPB and lysyl endopeptidase and
      chymotrypsin A digestion of endo-beta-galactosidase-digested ZPB. From sugar
      mapping analysis of the carbohydrate chains from these glycopeptides and
      comparison with the carbohydrate structures of the main intact neutral N-linked
      chains of ZPB/ZPC, the triantennary and tetraantennary chains were shown to be
      localized mainly at Asn220 of ZPB, and diantennary chains were present on all the
      three potential residues (Asn203, Asn220 and Asn333). These results suggest that
      the carbohydrate chains linked to Asn220 of ZPB participate predominantly in
      sperm-egg binding.

PMID- 9546666
TI  - Three-dimensional structure of moenomycin A--a potent inhibitor of penicillin
      binding protein 1b.
AB  - The first three-dimensional structure of moenomycin A in aqueous solution based
      on NMR-derived distance constraints and molecular dynamics simulations is
      presented. The antibiotic moenomycin A was obtained from the FlavomycinR complex
      by ultrafiltration, chromatography on a DEAE-cellulose ion exchanger and reverse
      phase chromatography in 98% purity. In contrast to the previously reported
      behaviour, the compound gave rise to well-resolved NMR spectra in standard
      solvents. Using several two-dimensional experiments, a complete assignment of
      proton and carbon chemical shifts was achieved in (CD3)2SO, CD3OD and H2O/D2O
      (9:1, pH 7.3). A total of 175 interproton distances were determined from 600-MHz
      rotating-frame NOE (ROE) spectra and were used as restraints in molecular
      dynamics calculations. These restraints included 84 ROEs between protons of the
      moenocinol part leading to a very well-defined structure of the lipid part of the
      molecule. The relative orientation of the subunits was determined by 66 ROEs
      among different sugar rings and between the sugar rings and moenocinol. As a
      result of the molecular dynamics calculation, rings D, E, and F as well as the
      moenocinol part are very well-defined (average rms deviation over all heavy atoms
      0.48 A) whereas rings A, B and C display a higher degree of conformational
      flexibility which might be an artefact due to the lower number of ROEs in this
      part of the molecule. A three-dimensional pharmacophore hypothesis comprising
      functional groups of rings E and F and the carboxyl group of glyceric acid is
      presented on the basis of the degradation and derivatization studies of Welzel
      and coworkers [Welzel, P., Kunisch, F., Kruggel, F., Stein, H., Scherkenbeck, J.,
      Hiltmann, A., Duddeck, H., Muller, D., Maggio, J. E., Fehlhaber, H.-W., Seibert,
      G., van Heijenoort, Y. & van Heijenoort, J. (1987) Moenomycin A: Minimum
      structural requirements for biological activity, Tetrahedron 43, 585-598; Welzel,
      P. (1993) Transglycosylase inhibition, in Antibiotics and antiviral compounds-
      Chemical synthesis and modifications (Krohn, K., Kirst, H. A. & Maag, H., eds)
      pp. 373-378, VCH Weinheim].

PMID- 9546667
TI  - Effect of the extramitochondrial adenine nucleotide pool size on oxidative
      phosphorylation in isolated rat liver mitochondria.
AB  - The effect of the concentration of extramitochondrial adenine nucleotides on
      oxidative phosphorylation was studied in isolated rat liver mitochondria.
      Mitochondria were incubated with succinate and hexokinase or creatine kinase at
      constant or varying extramitochondrial adenine nucleotide concentrations ranging
      over 0.3-5 mM. As parameters of oxidative phosphorylation, rate of respiration,
      membrane potential as well as intra- and extra-mitochondrial adenine nucleotide
      concentrations were determined. Below a threshold concentration of
      extramitochondrial adenine nucleotides of 2 mM, the free Gibb's energy for the
      adenine nucleotide transport increased but the extramitochondrial ATP/ADP ratio
      decreased at intermediate rates of respiration with decreasing extramitochondrial
      adenine nucleotide concentrations. In this range the rate of respiration was
      dependent on the extramitochondrial ADP concentration. No effect of the
      extramitochondrial adenine nucleotide concentration on the relationships between
      the rate of respiration and the membrane potential, the intramitochondrial
      adenine nucleotide pool and the intramitochondrial ATP/ADP ratio was found. This
      suggests that the decline of extramitochondrial ATP due to adenine nucleotide
      degradation and the limitation of adenine nucleotide transport may be of
      importance in the postischemic phase as nucleotide resynthesis and reorganization
      of physiological ion distribution are ATP consuming processes.

PMID- 9546668
TI  - Biosynthesis of C18 polyunsaturated fatty acids in microsomal membrane
      preparations from the filamentous fungus Mucor circinelloides.
AB  - The biosynthesis of C18 polyunsaturated fatty acids has been studied in the
      fungus Mucor circinelloides. Microsomal membrane preparations contained delta9,
      delta12 and delta6 desaturase activities. The delta9 desaturase exhibited
      characteristics similar to those of the animal and yeast delta9 desaturases in
      being membrane bound and utilising stearoyl-CoA as substrate. Cytochrome b5 (a
      soluble form lacking the 20-amino-acid hydrophobic C-terminus) stimulated
      desaturation and was identified as a major cytochrome component of the membranes.
      A high ferricyanide reductase activity (indicative of NADH:cytochrome b5
      reductase activity) coupled to inhibition by cyanide further supported the
      similarity with the mammalian and yeast enzymes. Time-course studies with
      radiolabelled oleoyl-CoA showed that the oleate [18:1(9)] was transferred to
      position sn-2 of phosphatidylcholine (PtdCho) and was desaturated to linoleoyl
      PtdCho. Removal of the excess oleoyl-CoA from the membranes prior to addition of
      reductant confirmed that oleoyl-PtdCho is a substrate for the delta12 desaturase.
      The entry of oleate at this position of the phospholipid was facilitated by the
      activity of lyso-PtdCho:acyl-CoA acyltransferase (LPCAT), which readily
      transferred oleate from oleoyl-CoA to lyso-PtdCho. Desaturation of oleate at the
      sn-1 position of PtdCho was also demonstrated after the entry of oleate in to the
      phospholipid by the enzymes of the Kennedy pathway. Thus oleate at sn-1 and sn-2
      positions served as substrate for the delta12 desaturase and is consistent with
      observations in oil seed tissues. LPCAT activity was substantially higher than
      that observed with lysophosphatidylethanolamine:acyl-CoA acyltransferase (LPEAT)
      indicating that oleate is less effectively channelled to phosphatidylethanolamine
      for linoleate synthesis. No desaturation on phosphatidylinositol could be
      demonstrated. Delta6 desaturase utilised linoleate at the sn-2 position of
      exogenously supplied PtdCho presented to the membranes in the presence of
      reductant. Thus, the entry of substrates into PtdCho via LPCAT and the synthesis
      of linoleate [18:2(9,12)] and gamma-linolenate [18:3(6,9,12)] on this
      phospholipid is similar to that reported for oil seed membranes.

PMID- 9546669
TI  - Analysis of stress in the active site of myosin accompanied by conformational
      changes in transient state intermediate complexes using photoaffinity labeling
      and 19F-NMR spectroscopy.
AB  - Myosin forms stable ternary complexes with ADP and the phosphate analogues,
      fluoroaluminate (Al F4-), fluoroberyllate (BeFn) or orthovanadate (Vi); these
      ternary complexes mimic transient intermediates in the myosin ATPase cycle.
      Moreover, we previously demonstrated that these complexes may mimic different
      myosin ATPase reaction intermediates corresponding to separate steps in the cross
      bridge cycle [Maruta, S., Henry, G. D., Sykes, B. D. & Ikebe, M. (1993) J. Biol.
      Chem. 268, 7093-7100]. Park et al. suggested that the changing conformation of
      ATP during hydrolysis stresses the active site of myosin subfragment-1 (S-1)
      through protein-nucleotide contacts at the gamma-phosphate and nucleotide base,
      and the stress-induced strain in the cross-bridge may be the mechanism by which
      energy in ATP is transferred to the myosin structure [Park, S., Ajtai, K. &
      Burghardt, T. P. (1997) Biochemistry 36, 3368-3372]. In the present study, the
      photoactive ADP analogue, 3'-O-(N-methylanthraniloyl)-2-azido-ADP (Mant-2-N3
      ADP), and the 19F-labeled ADP analogue, 2
      [(trifluoromethylnitrophenyl)aminoethyl]diphosphate, were employed to examine
      conformational differences in protein-nucleotide contact in the ATP-binding site
      that may correlate with energy transduction. Mant-2-N3-ADP was trapped within the
      active site of skeletal and smooth muscle myosin in the presence of AlF4-, BeFn
      or Vi. For both skeletal and smooth muscle myosins, trapped Mant-2-N3-ADP was
      covalently linked to the 25-kDa N-terminal fragment of S-1 of both myosin/Mant-2
      N3-ADP/AlF4- and BeFn complexes, presumably at Trp130. However, the efficiency of
      the incorporation was much higher for skeletal than for smooth muscle myosin
      suggesting that the conformations of the adenine-binding pockets of the two
      myosins are somewhat different. Although the amount of Mant-2-N3-ADP trapped in
      the presence of AlF4- and BeFn was the same for both myosins, the efficiency of
      photolabeling skeletal muscle myosin was approximately two times higher for BeFn
      complex than for AlF4- complex. The 19F-NMR spectra of the bound 2
      [(trifluoromethylnitrophenyl)aminoethyl]diphosphate in the ternary complexes
      formed in the presence of AlF4-, BeFn or Vi showed small but distinguishable
      differences. Taken together, these results indicate that there is some variation
      in the protein-nucleotide contacts at the nucleotide base among the ternary
      complexes studied, and these differences mimic separate steps occurring
      transiently during the contractile cycle.

PMID- 9546670
TI  - One-step purification of cathepsin D by affinity chromatography using immobilized
      propeptide sequences.
AB  - In vivo, active cathepsin D proteinase is generated by removal of a 44-residue
      propeptide at its N-terminus. Here we report that mature cathepsin D and
      pseudocathepsin D (a partially activated form of cathepsin D with 25 amino acid
      residues removed from the propeptide) bind to the immobilized propeptide, while
      procathepsin D does not. The N-terminal 25 amino acid residues of the propeptide
      are sufficient for this binding. Based on this observation, a simple one-step
      procedure was developed to purify mature cathepsin D from whole cell extracts to
      near homogeneity. This method has the advantage over existing affinity
      purification systems that active forms of the proteinase can be separated from
      inactive precursors and other aspartic proteinases. Furthermore, this technique
      was effective for pepsin as well, suggesting it may have general utility for all
      activated aspartic proteinases and perhaps other families of proteinases.

PMID- 9546671
TI  - Non-detergent sulphobetaines enhance the recovery of membrane and/or cytoskeleton
      associated proteins and active proteases from erythrocytes infected by Plasmodium
      falciparum.
AB  - A better understanding of the causative agent's biology and the definition of new
      targets for the development of drugs and/or specific immune responses is
      necessary to face the spred of drug-resistant malaria in developing countries and
      the absence of an efficient vaccine against this most important infectious
      disease. Non-detergent sulphobetaines enhance the recovery and isoelectric
      focussing of active Plasmodium falciparum proteases, cytoskeleton-associated
      proteins and Maurer's cleft-associated proteins. This is a significant advantage
      for the purification of such proteins and might help pinpoint their role for red
      blood cell rupture and merozoite release.

PMID- 9546672
TI  - Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein
      kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of
      antibody AT100 and requires a paired-helical-filament-like conformation.
AB  - AT100 is a monoclonal antibody highly specific for phosphorylated Tau in
      Alzheimer paired helical filaments. Here we show that the epitope is generated by
      a complex sequence of sequential phosphorylation, first of Ser199, Ser202 and
      Thr205 (around the epitope of antibody AT8), next of Thr212 by glycogen synthase
      kinase (GSK)-3beta (a proline-directed kinase), then of Ser214 by protein kinase
      A (PKA). Conversely, if Ser214 is phosphorylated first it protects Thr212 and the
      Ser-Pro motifs around the AT8 site against phosphorylation, and the AT100 epitope
      is not formed. The generation of the AT100 epitope requires a conformation of tau
      induced by polyanions such as heparin, RNA or poly(Glu), conditions which also
      favor the formation of paired helical filaments. The Alzheimer-like
      phosphorylation can be induced by brain extracts. In the extract, the kinases
      responsible for generating the AT100 epitope are GSK-3beta and PKA, which can be
      inhibited by their specific inhibitors LiCl and RII, respectively. A cellular
      model displaying the reaction with AT100 is presented by Sf9 insect cells
      transfected with Tau. Knowledge of the events and kinases generating the AT100
      epitope in cells might allow us to study the degeneration of the cytoskeleton in
      Alzheimer's disease.

PMID- 9546673
TI  - Selection of a RNA aptamer that binds to human activated protein C and inhibits
      its protease function.
AB  - A high-affinity RNA aptamer to human activated protein C (APC) was selected from
      a pool of random sequences using in vitro selection. Activated protein C, a
      trypsin-like serine protease plays an important role along with thrombin as a
      regulator in blood clotting cascade. After seven rounds of selection and
      amplification, a single predominant nucleic acid sequence APC-167, a 167-base
      oligonucleotide with a random sequence core of 120 bases, was obtained. The
      selected aptamer did not bind to thrombin or factor Xa and thus demonstrated
      specificity to APC. Furthermore, this aptamer was a non-competitive inhibitor to
      the cleavage reaction of a fluorogenic substrate catalyzed by APC. The inhibition
      constant (Ki) of APC-167 was 83 nM. The 99-base oligonucleotide (APC-99) derived
      from APC-167 by deleting both primer binding sites, was also found to inhibit APC
      strongly (Ki = 137 nM). Two stem-loop structures and at least one G x U wobble
      base pair in the stem were elucidated as important structural motifs for binding.

PMID- 9546674
TI  - Lipocalins of boar salivary glands binding odours and pheromones.
AB  - Large amounts of an odorant-binding protein have been isolated from submaxillary
      glands of mature male pig. This polypeptide molecule is sex-specific, being
      absent in females. On electrophoretic gels under denaturing conditions it
      migrated as a broad band with an apparent molecular mass of around 20 kDa.
      Electrospray mass spectrometry revealed the presence of three main components,
      whose mass differences are not interpretable as result of any common post
      translational modifications, indicating the presence of distinct polypeptide
      chains. N-terminal Edman degradation yielded a single sequence of 29 amino acids.
      It includes the lipocalin signature (-G-X-W-) and shows clear homology with a
      subclass of odorant-binding proteins present in mouse saliva, nasal mucus and
      urine. The purified protein still retained small ligands tightly bound; among
      them 5alpha-androst-16-en-3-one and 5alpha-androst-16-en-3alpha-ol, both known
      sex pheromones for the pig, were identified. The protein also binds 2-isobutyl-3
      methoxypyrazine, a good ligand for most odorant-binding proteins, with a
      dissociation constant of 5 microM.

PMID- 9546675
TI  - Purification and amino acid sequence of halystase from snake venom of Agkistrodon
      halys blomhoffii, a serine protease that cleaves specifically fibrinogen and
      kininogen.
AB  - We have isolated a serine protease, halystase, from Agkistrodon halys blomhoffii
      venom by chromatography on DEAE-Sepharose, heparin-Sepharose and Q-Sepharose
      columns, and have determined the complete amino acid sequence by Edman
      degradation and by mass spectral analysis of peptides generated by enzymatic and
      chemical cleavage. The 238-residue sequence of halystase, containing N-linked
      carbohydrates (about 13%) at two sites showed significant similarity to other
      thrombin-like snake venom serine proteases (66-72%), mammalian tissue kallikrein
      (42%) and thrombin (26%). Halystase contained the tentative catalytic triad of
      His43, Asp88 and Ser184 common to all serine proteases and Asp178 in the primary
      substrate-binding site. Although halystase contained an RGD sequence at residues
      181-183, it did not inhibit platelet aggregation induced by ADP or collagen. It
      hydrolyzed most efficiently a tissue-kallikrein substrate,
      prolylphenylalanylarginyl-4-methyl-coumaryl-7-amide, and released bradykinin from
      bovine kininogen. Halystase did not coagulate human plasma, but it cleaved the
      fibrinogen B beta chain at the carboxyl side of Arg42 and cleaved slowly the
      fibrogen A alpha chain. Fibrinogen thus treated gradually became insensitive to
      thrombin. The proteolytic activity was inhibited with diisopropyl
      fluorophosphate, phenylmethylsulfonyl fluoride or leupeptin. These results
      indicate that halystase is a serine protease structurally similar to coagulating
      thrombin-like snake venom proteases, but it specifically cleaves fibrinogen at
      sites different from thrombin without inducing fibrin clotting, and hydrolyzes
      kininogen to produce bradykinin, resulting in the reduction of blood pressure.

PMID- 9546676
TI  - Selective reduction of 6-O-sulfation in heparan sulfate from transformed mammary
      epithelial cells.
AB  - Heparan sulfate at cell surfaces and in the extracellular matrix regulates cell
      proliferation and adhesion by binding to growth factors and matrix proteins via
      structurally specific oligosaccharide domains. We have used the hormonally
      regulated mouse mammary carcinoma cell line S115 as a model to elucidate the
      effect of malignant transformation on the structure of heparan sulfate. When
      cultured in the presence of testosterone, S115 cells form tumor cell colonies in
      soft agar and exhibit fibroblast-like morphology; withdrawal of testosterone
      results in a loss of the tumorigenic capacity and a switch towards epithelial
      morphology. Metabolically 35SO4-labeled heparan sulfate was isolated from
      testosterone-treated and non-treated S115 cells and subjected to structural
      analysis. We found that the testosterone-dependent malignant transformation was
      associated with reduced sulfation of heparan sulfate due to a approximately 40%
      decrease in the amount of GlcN6S units. By contrast, no significant differences
      were observed in the amounts of 2-O-sulfate or N-sulfate groups. The reduced 6-O
      sulfation of GlcN units in heparan sulfate from transformed S115 cells led to a
      marked decrease in the amount of trisulfated IdoA2S-GlcNS6S units (IdoA, L
      iduronic acid), implicated in many heparan sulfate-protein interactions.

PMID- 9546677
TI  - Demonstration of a Ca2+ requirement for thyroglobulin dimerization and export to
      the golgi complex.
AB  - We have examined the effects of depleting the endoplasmic reticulum Ca2+ store on
      the maturation of newly synthesized thyroglobulin molecules, their export to the
      Golgi complex, and their secretion by FRTL-5 cells. An inhibitor of the
      endoplasmic reticulum Ca2+ pump, thapsigargin, and the Ca2+ ionophore A23187
      depleted the endoplasmic reticulum Ca2+ store and strongly inhibited
      thyroglobulin secretion in cells chased in medium containing 0.1 mM Ca2+.
      Inhibition of thyroglobulin secretion was caused by a block in the export of
      newly synthesized thyroglobulin molecules from the endoplasmic reticulum to the
      Golgi complex, as shown by cell-fractionation experiments and the intracellular
      accumulation of endoH-sensitive thyroglobulin. The thyroglobulin molecules
      retained in the endoplasmic reticulum of cells treated with the drugs were found
      to assemble more slowly into dimers than thyroglobulin in control cells. Protease
      sensitivity experiments demonstrated that thyroglobulin dimers assembled in the
      presence of thapsigargin had a different conformation with respect to dimers
      assembled in controls cells.

PMID- 9546678
TI  - Guanylate-cyclase-inhibitory protein is a frog retinal Ca2+-binding protein
      related to mammalian guanylate-cyclase-activating proteins.
AB  - Two guanylate-cyclase-activating proteins (GCAP) encoded by a tail-to-tail gene
      array have been characterized in the mammalian retina. Using frog retina as a
      model, we obtained evidence for the presence of a photoreceptor Ca2+-binding
      protein closely related to GCAP. This protein (206 amino acids) does not
      stimulate guanylate cyclase (GC) in low [Ca2+], but inhibits GC in high [Ca2+],
      and is therefore termed guanylate-cyclase-inhibitory protein (GCIP). Sequence
      analysis indicates that GCIP and GCAP1 and GCAP2 have diverged substantially, but
      conserved domains present in all vertebrate GCAP are present in GCIP. Moreover,
      partial characterization of the GCIP gene showed that the positions of two
      introns in the GCIP gene are identical to positions of corresponding introns of
      the mammalian GCAP gene array. As to the major differences between GCIP and GCAP,
      the fourth EF hand Ca2+-binding motif of GCIP is disabled for Ca2+ binding, and
      GCIP does not stimulate GC. Monoclonal and polyclonal antibodies raised against
      recombinant GCIP identified high levels of GCIP in the inner segments, somata and
      synaptic terminals of frog cone photoreceptors. The results suggest that GCIP is
      a Ca2+-binding protein of the GCAP/recoverin subfamily. Its localization in frog
      cones closely resembles that of GC in mammalian cones. GCIP inhibits GC at high
      free [Ca2+], competing with GCAP1 and GCAP2 for GC regulatory sites.

PMID- 9546679
TI  - Tryptophan mutants of troponin C from skeletal muscle--an optical probe of the
      regulatory domain.
AB  - We have generated a series of chicken skeletal muscle troponin C mutants to study
      the conformation of the regulatory domain in the N-terminal half of the molecule.
      These mutants each contained a single Trp at position 22 (helix A), 52 (linker of
      helices B and C), or 90 (central helix). Some of these mutants also contained
      additional mutations to introduce a single Cys at a desired position. The mutants
      were characterized by molecular graphics and CD and found to have a minimum of
      structural perturbations when compared with the native structure. They also
      retained the ability to regulate myofibrillar ATPase activity. The fluorescence
      of Trp22 was sensitive to Ca2+ binding only to the regulatory sites, whereas
      Trp52 and Trp90 responded to Ca2+ binding to both the regulatory and the
      Ca2+/Mg2+ sites. The tryptophan quantum yield (Q) of all Trp22-containing mutants
      was very high (0.33) in the absence of bound Ca2+, compared to that of L
      tryptophan in aqueous solution (0.14). Q decreased 25% upon binding of Ca2+ to
      the regulatory sites. The quantum yields of Trp52 and Trp90 in apo mutants were
      close to 0.14. In the presence of bound Ca2+ at the regulatory sites, the quantum
      yield of Trp52 decreased 16%, whereas that of Trp90 increased 25%. Results from
      acrylamide quenching of the fluorescence of the three Trp residues indicated that
      Trp22 was the least exposed and Trp52 was the most exposed, consistent with other
      spectral data that Trp22 was in a relatively nonpolar environment and Trp52 was
      in a highly polar environment. The ability of Trp52 and Trp90 to sense Ca2+
      binding to sites located at both domains suggests inter-domain communication in
      the protein. These single Trp TnC mutants provide specific signals for probing
      Ca2+-induced conformational changes in the regulatory domain.

PMID- 9546681
TI  - Advances in the understanding of the nephrotoxicity of radiocontrast media.

PMID- 9546680
TI  - How Drosophila species acquire cold tolerance--qualitative changes of
      phospholipids.
AB  - Phospholipids of many cold-tolerant organisms have been reported to contain more
      unsaturated fatty acids than cold-susceptible organisms, a phenomenon known to
      maintain membrane fluidity at low temperature. However, we have obtained results
      to the contrary through a comparison of the membrane phospholipids of six
      temperate and subtropical species belonging to the Drosophila melanogaster
      species group. With enhancement of cold tolerance, the percentages of monoenoic
      acids increased but the percentages of dienoic acids decreased, that is, the
      number of double bonds in the phospholipid decreased without a marked variation
      in the percentages of unsaturated fatty acids. Concomitantly, the percentage of
      fatty acids containing 16 carbon atoms increased, while that of fatty acids with
      18 carbon atoms decreased. Since phosphatidylethanolamine is a dominant
      phospholipid in Drosophila, these changes probably contribute to keeping the
      homeoviscosity of the cellular membranes in a manner different to that in
      phosphatidylcholine-rich membranes, thereby increasing cold tolerance.

PMID- 9546683
TI  - The relationship between pentosidine and hemodialysis-related connective tissue
      disorders.
AB  - Dialysis-related amyloidosis (DRA), such as destructive spondyloarthropathy (DSA)
      and carpal tunnel syndrome (CTS), occurs in the connective tissues of patients on
      long-term hemodialysis (HD). Recently, it was suggested that advanced glycation
      end products (AGEs) and beta2-microglobulin (beta2m) modified with AGEs are
      related to DRA. The aim of this study is to elucidate whether serum levels of
      pentosidine, which is an AGE, relate to the occurrence of DRA in patients with
      long-term HD. 127 end-stage renal failure patients, with DSA or CTS and
      undergoing HD, were examined. Serum pentosidine was measured by the HPLC method
      with column switching. Beta2m and intact parathyroid hormone (i-PTH) were
      measured. Pentosidine levels were significantly elevated in the DSA, CTS, and DRA
      groups (patients in the DRA group had either DSA and/or CTS). There were no
      significant differences in the beta2m and i-PTH levels between any group. The
      duration of HD did not correlate with either pentosidine or beta2m levels, but
      did with i-PTH. Receiver-operating characteristic (ROC) analysis was performed to
      examine the discriminatory ability of pentosidine, beta2m, and i-PTH for DRA. The
      area under the ROC curve was the greatest for pentosidine. Serum beta2m levels
      were not related with the occurrence of DRA. The fact that serum pentosidine was
      higher in DRA than in non-DRA indicates that it has potential as an indicator of
      the occurrence of DRA in long-term HD patients.

PMID- 9546682
TI  - Improvement of nutritional status in patients receiving maintenance hemodialysis
      after correction of renal anemia with recombinant human erythropoietin.
AB  - Despite a large body of evidence showing the beneficial effects of successful
      treatment of anemia with recombinant human erythropoietin (EPO) in patients with
      end-stage renal disease, controversy remains as to whether EPO treatment of
      anemia can improve the nutritional status in patients on maintenance
      hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis
      patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased
      for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then
      titrated in the following 12 weeks to maintain the target value. Nutritional
      status was assessed at baseline and after 6 months of follow-up, using the global
      protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low
      global PCM score indicates better nutrition. The results showed that hemoglobin
      values significantly increased from 8.7 +/- 0.8 g/dl at baseline to 10.7 +/- 0.5
      g/dl in the 6th month (p < 0.001). No significant changes were observed in the
      normalized protein catabolic rate and Kt/V during the study period. Global PCM
      scores improved from 30.0 +/- 7.5 to 23.6 +/- 3.1 (p < 0.001) and paralleled the
      correction of anemia by EPO treatment. The data were consistent with a major
      improvement in the nutritional markers of relative body weight, triceps skinfold,
      midarm circumference, midarm muscle circumference, serum albumin, serum
      transferrin and total lymphocyte count in the 6th month as compared to baseline.
      The percentages of mild and moderate-severe PCM at baseline were 32 and 58%,
      respectively. These percentages were significantly reduced during the 6th month
      to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia
      with EPO improves the nutritional status in hemodialysis patients. A postulated
      mechanism is that EPO may exhibit anabolic effects, with a better utilization of
      ingested protein.

PMID- 9546684
TI  - Association of apolipoprotein E polymorphism with lipoprotein glomerulopathy.
      Report of 2 cases with a new genotype and comparison of the relative frequencies
      of apolipoprotein E isoforms in lipoprotein glomerulopathy and in the general
      population.
AB  - Two cases of lipoprotein glomerulopathy with a new apolipoprotein E (Apo E)
      genotype, epsilon3/epsilon4, were diagnosed recently. These 2 cases, together
      with other cases documented in English literature made a total of 6 common
      isoforms of Apo E encountered in lipoprotein glomerulopathy. Although the
      calculated allele frequency of epsilon2 is relatively high in cases with
      lipoprotein glomerulopathy as compared with that in the general population (39.3
      vs. 6.4-11.4%), the gradual emergence of Apo E isoforms other than E2/E3 in
      lipoprotein glomerulopathy implicates that the genetic susceptibility of certain
      Apo E isoforms may not be a crucial factor. An alteration in the local
      environment of glomerular capillaries may be more important in the pathogenesis
      of lipoprotein glomerulopathy.

PMID- 9546685
TI  - Lipid composition of platelets in patients with uremia.
AB  - AIMS: The lipid composition of platelets and the function of these cells in
      patients with uremia were studied. METHODS: Fourteen patients and 14 normal
      volunteers were studied. Platelet lipids including phospholipids and cholesterol,
      as well as the platelet aggregation response to agonists, were studied. RESULTS:
      The amount of platelet phospholipids was decreased in patients compared to
      controls (338.0 +/- 79 vs. 511.6 +/- 125 nmol/10(9) cells; p < 0.001), while the
      percentage of the five main specimens of these compounds was normal. The content
      of platelet cholesterol in patients (97.8 +/- 17.0 microg/10(9) cells) was
      similar to that in controls (91.7 +/- 26.0 microg/10(9) cells). Consequently, the
      cholesterol:phospholipid ratio in uremic platelets was increased (0.75 +/- 0.1
      vs. 0.46 +/- 0.1; p < 0.01). Although this feature is associated with
      hyperreactive platelets, the aggregation tests were defective for adenosin
      diphosphate (p < 0.01), arachidonic acid (p < 0.01), epinephrine (p < 0.01) and
      collagen (p < 0.001). This behavior is probably due to the multifactorial
      platelet defect described in uremia.

PMID- 9546686
TI  - Accidental aluminum intoxication in patients undergoing acetate-free
      biofiltration.
AB  - Eight patients undergoing acetate-free biofiltration (AFB) suffered aluminum
      intoxication. The source of this outbreak was parenteral exposition to high
      concentrations of aluminum in sodium bicarbonate solutions. The manufacturer of
      bicarbonate solutions used in AFB was substituted in May 1994 and the solutions
      were stored in glass containers. At the peak of intoxication (July 1994) serum
      aluminum determination revealed an average value of 147.3 +/- 21 microg/l.
      Aluminum levels in bicarbonate solutions were 400 microg/l. Serum ferritin rose
      from 307.4 +/- 161 to 735.6 +/- 206 ng/ml, whereas MCV decreased significantly
      from 98.4 +/- 9 to 90.1 +/- 10 fl. No significant changes were found in
      hemoglobin, neither in plasma iron, nor in iron transferrin saturation. The doses
      of recombinant human erythropoietin showed a considerable increase. The
      replacement solutions were changed and a new solution, stored in plastic
      containers and with aluminum levels lower than 10 microg/l, was used. The
      biochemical parameters were normalized. This outbreak demonstrates the need for a
      stringent control of aluminum-containing replacement fluids.

PMID- 9546687
TI  - Anticardiolipin antibodies in classic pediatric hemolytic-uremic syndrome: a
      possible pathogenic role.
AB  - Anticardiolipin (aCL) antibodies have been associated with thrombocytopenia,
      hemolytic anemia and an increased risk of thrombosis in different vascular
      locations, even in the absence of lupus. The classic hemolytic-uremic syndrome is
      a postinfectious acute renal failure characterized by hemolytic anemia,
      thrombocytopenia and the presence of widespread glomerular thrombosis in the
      kidney, with pathogenic mechanisms that remain to be identified. In order to
      establish the frequency of aCL antibodies in this syndrome and to identify a
      possible role in the pathogenesis and clinical manifestations, 17 patients were
      studied during the reactant phase of the disease looking for an association
      between the presence of aCL antibodies (isotypes IgG, IgA and IgM) and the main
      clinical variables of the syndrome. In 8 patients IgG aCL was present, 2 patients
      had IgM aCL, and 1 had IgA antibodies on the solid-phase ELISA aCL assays, but no
      association could be demonstrated with the clinical variables studied. Although
      it might correspond to an epiphenomenon related to the triggering intestinal
      infection, a pathogenic role cannot be discarded and additional studies should be
      performed.

PMID- 9546688
TI  - Mesangial expression of a nonmuscle myosin heavy chain, SMemb, is associated with
      glomerular sclerosis and renal prognosis in IgA nephropathy.
AB  - To characterize the phenotypic alteration in mesangial cells in human
      glomerulonephritis, we investigated the expression of nonmuscle-type myosin heavy
      chain, SMemb, and alpha-smooth muscle actin (alpha-SM actin) in IgA nephropathy.
      The expression of SMemb and alpha-SM actin was examined by immunohistochemistry
      in biopsy specimens from 45 patients with IgA nephropathy. We examined a total of
      489 glomeruli representing all patients enrolled, and found that mesangial
      expression of SMemb and alpha-SM actin was associated with mesangial
      proliferation. Only mesangial expression of SMemb showed a significant
      relationship with mesangial matrix accumulation. Semiquantitative evaluation
      using composite expression scores showed that the expression of SMemb was
      elevated in the patients with poor renal prognosis. The expression of alpha-SM
      actin showed no significant relationship with renal prognosis. These results
      suggest that mesangial expression of SMemb is an important factor in the
      progression of IgA nephropathy, and that SMemb and alpha-SM actin are associated
      with the activation of mesangial cells by different mechanisms.

PMID- 9546689
TI  - Sera of IgA nephropathy patients contain a heterogeneous population of relatively
      cationic alpha-heavy chains.
AB  - Sera of IgA nephropathy (IgAN) patients and normal subjects were analysed by two
      dimensional (2-D) gel electrophoresis. Densitometric analysis of the 2-D gels of
      IgAN patients and normal subjects revealed that their protein maps were
      comparable. There was no shift of pI values in the major alpha-heavy chain spots.
      However, the volume of the alpha-heavy chain bands were differently distributed.
      Distribution was significantly lower at the anionic region in IgAN patients (mean
      anionic:cationic ratio of 1.184 +/- 0.311) as compared to normal healthy controls
      (mean anionic:cationic ratio of 2.139 +/- 0.538). Our data are in support of the
      previously reported findings that IgA1 of IgAN patients were lacking in sialic
      acid residues.

PMID- 9546690
TI  - Development of calcium oxalate crystals on urothelium: effect of free radicals.
AB  - The effects of free radicals on the development of crystals attached to the
      living epithelium have been studied using an experimental model that enables
      close simulation of the conditions prevailing in the kidney. The results obtained
      clearly demonstrate that free radical-damaged cells produce a favorable
      environment for crystal development. At low free radical concentrations, crystals
      develop on calcium-enriched zones, whereas at higher concentrations, crystals
      develop on areas with a destroyed monolayer of superficial cells. Evaluation of
      the action of some products with antioxidant action and/or crystallization
      inhibitory capacity is also included. Antioxidants, such as ascorbic acid and
      mannitol, exerted the most remarkable effects in avoiding calcium oxalate crystal
      development, whereas crystal inhibitors, such as citric acid, did not produce any
      remarkable reduction in calcium oxalate crystallization. Phytic acid notably
      decreased calcium oxalate crystal development. The ability of phytic acid to
      diminish calcium oxalate crystallization must be attributed to the combination of
      its inhibitory capacity of calcium oxalate crystallization and its preventive
      antioxidant action.

PMID- 9546691
TI  - Urinary transforming growth factor-beta (TGF-beta) excretion and renal production
      of TGF-beta in rats with subtotal renal ablation: effect of enalapril and
      nifedipine.
AB  - The aim of the present study was to investigate the effect of enalapril and
      nifedipine on renal transforming growth factor-beta (TGF-beta) production and on
      the rate of urinary TGF-beta excretion in rats with subtotal renal ablation.
      After subtotal nephrectomy some animals were treated with enalapril or
      nifedipine. Renal cortical TGF-beta mRNA levels were 68% higher in untreated
      nephrectomized rats (p < 0.05) and 39% higher in rats treated with nifedipine (p
      < 0.05) compared with controls. There was no difference in renal cortical TGF
      beta mRNA content between the nephrectomized rats treated with enalapril and sham
      animals, showing that enalapril treatment prevented the increase of TGF-beta mRNA
      in nephrectomized rats. The rate of urinary TGF-beta excretion was 2.2 +/- 0.8
      pg/min in sham animals, 61.5 +/- 40.1 pg/min in untreated nephrectomized rats,
      9.6 +/- 4.2 pg/min in nephrectomized rats treated with enalapril, and 55.2 +/-
      24.46 pg/min in rats treated with nifedipine. The immunohistochemical reaction
      for TGF-beta in the renal cortex was less intense in the nephrectomized rats
      treated with enalapril than in the other groups of rats with subtotal renal
      ablation. These data show that enalapril induces a decrease in renal TGF-beta
      production and in urinary TGF-beta excretion in rats with subtotal renal
      ablation, an effect associated with the protective action of this treatment on
      renal structure and function and suggest that the determination of the rate of
      urinary TGF-beta could be a useful procedure for the evaluation of disease
      progression and therapeutic efficacy in the remnant kidney model.

PMID- 9546692
TI  - Anti-CD8 monoclonal antibody protects against spontaneous IgA nephropathy in ddY
      mice.
AB  - We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/or anti-CD8
      mAb in ddY mice, an animal model of spontaneous IgA nephropathy. Female ddY mice
      were treated with 18 intravenous injections of anti-CD4 and/or anti-CD8 mAb at 2
      week intervals. This was based on our observation that a single injection of anti
      CD4 mAb or anti-CD8 mAb caused a selective depletion in CD4+ T cells for 2 weeks
      and CD8+ T cells for 4 weeks, respectively. The level of proteinuria, serum IgA,
      and changes in the histopathological features of renal tissue samples were
      assessed in treated mice between the age of 4 and 40 weeks. The level of
      proteinuria increased with age, but there was not significant difference among
      the groups. No animal developed microhematuria throughout the study. Treatment
      with anti-CD4 mAb produced a mild to moderate level of mesangial hypertrophy at
      20 and 40 weeks, similar to the results in untreated mice. The lowest degree of
      mesangial hypertrophy occurred in mice treated with anti-CD8 mAb up to the age of
      40 weeks. Treatment with a combination of anti-CD4 and anti-CD8 mAbs produced
      effects that were similar to those observed on treatment with anti-CD8 mAb alone.
      Our results suggest that CD8+ T cells mediate mesangial proliferation and the
      progression of nephropathy in ddY mice.

PMID- 9546694
TI  - Castleman's disease and mesangial proliferative glomerulonephritis: the role of
      interleukin-6.
AB  - Renal complications of Castleman's disease (angiofollicular lymph node
      hyperplasia) are uncommon. The reported cases are very heterogeneous and their
      renal pathology ranged from minimal change disease, mesangial proliferative
      glomerulonephritis, to amyloidosis. We have previously reported two cases of
      Castleman's disease with renal complications. We now present two more such cases.
      In contrast to other reports, all our cases are of the plasma cell type and their
      renal pathology showed remarkable similarities, namely mesangial proliferation,
      interstitial plasma cell infiltration and negative immunofluorescence. The level
      of serum interleukin-6 (IL-6) in both patients was elevated at presentation and
      came down with immunosuppressive therapy.

PMID- 9546693
TI  - Crescentic glomerulonephritis due to rifampin treatment in a patient with
      pulmonary atypical mycobacteriosis.
AB  - A 64-year-old male was treated continuously with rifampin, isoniazid and
      streptomycin for pulmonary atypical mycobacteriosis, Mycobacterium kansasii. Five
      weeks after beginning the treatment, the patient suddenly developed acute renal
      failure. A renal biopsy showed crescentic lesions characteristic of rapidly
      progressive glomerulonephritis with moderate interstitial changes. Serum
      antirifampin antibody was detected, and the cessation of rifampin treatment was
      followed by a rapid spontaneous recovery of the patient's renal function. This
      is, to our knowledge, the first case of rapidly progressive crescentic
      glomerulonephritis associated with rifampin treatment where circulating
      antirifampin antibody is demonstrated and the renal function spontaneously
      improved after discontinuing rifampin treatment.

PMID- 9546695
TI  - Soyprotein diet therapy in renal disease.

PMID- 9546696
TI  - Does hypertension cause end-stage renal disease in older white patients?

PMID- 9546697
TI  - Excessive polyuria after renal transplantation.

PMID- 9546698
TI  - Acute rhabdomyolysis after bezafibrate re-exposure.

PMID- 9546699
TI  - Safe use of gemfibrozil in uremic patients on continuous ambulatory peritoneal
      dialysis.

PMID- 9546700
TI  - Urinary acidification and renal sodium handling in a case of renal Fanconi
      syndrome.

PMID- 9546701
TI  - Bone loss in children with idiopathic hypercalciuria.

PMID- 9546702
TI  - A case of unusual anomalies of the abdominal aorta, renovascular hypertension,
      and disappearance of hypertension right after nephrectomy: an incomplete Ask
      Upmark kidney?

PMID- 9546703
TI  - Prevalence of gallstone disease in hemodialysis patients.

PMID- 9546704
TI  - Nature of membrane, permeability, and biocompatibility in hemodialysis.

PMID- 9546705
TI  - Effects of amlodipine and enalapril alone and in combination on glomerular
      hemodynamics in a hypertensive patient with unilaterally contracted kidney.

PMID- 9546706
TI  - Effect of omeprazole on the urinary excretion of aluminum and phosphorus in
      chronic renal failure.

PMID- 9546707
TI  - Erythropoietin-induced epilepsy in hemodialysis patients?

PMID- 9546708
TI  - Microscopic poliangiitis and human immunodeficiency virus infection.

PMID- 9546709
TI  - Isolated diffuse mesangial sclerosis in three siblings.

PMID- 9546710
TI  - Antioxidant status in Balkan endemic nephropathy.

PMID- 9546711
TI  - Ultrasonographic evaluation of the bursae in patients with dialysis-related
      amyloidosis.

PMID- 9546712
TI  - An analysis of the effect of routine medications on hemodialysis vascular access
      survival.

PMID- 9546713
TI  - Hypertension, lipid abnormalities and cardiovascular changes in autosomal
      dominant polycystic kidney disease.

PMID- 9546714
TI  - Acute tubulo-interstitial nephritis and uveitis with anti-neutrophil cytoplasmic
      antibodies in an adult: an autoimmune disorder?

PMID- 9546715
TI  - Nitric oxide as a regulator of embryonic development.
AB  - The role of nitric oxide (NO) in activation of cGMP is well established. It has
      been proposed that the ratio of cAMP to cGMP may be important in the regulation
      of preimplantation embryonic growth and differentiation. Therefore, we determined
      the ability of murine preimplantation embryos to produce NO. In addition, NO as
      an endogenous smooth muscle relaxant and vasodilator is a candidate for
      involvement in embryo implantation because this process requires increased
      vascular permeability and uterine quiescence at the sites of blastocyst
      apposition. Nitrite assays, an indirect measure of NO production, indicate that
      preimplantation murine embryos produce NO. This production was reversibly
      inhibited by culture of embryos in medium containing a nonspecific NO synthase
      (NOS) inhibitor (NG-nitro-L-arginine). Additionally, inhibition of normal
      development was observed in embryos cultured with NOS inhibitor. NO levels
      increased in culture medium when ovariectomized progesterone-treated animals were
      exposed to estrogen for 1 h in utero. Such hormonal treatment induces
      implantation. These data indicate that NO levels are regulated by estrogen and
      may be important in regulation of implantation. In addition, these data
      demonstrate for the first time that NO production appears to be required for
      normal embryonic development.

PMID- 9546716
TI  - Transient exposure of rhesus macaque oocytes to calyculin-A and okadaic acid
      stimulates germinal vesicle breakdown permitting subsequent development and
      fertilization.
AB  - Exposure of mammalian oocytes to the protein phosphatase (PP)-1 (PP1) and PP2A
      inhibitor okadaic acid (OA) stimulates oocyte meiosis. However, treated oocytes
      do not develop beyond metaphase I (MI), and they display morphological
      aberrations. Experiments were conducted to define inhibitor treatment conditions
      for macaque oocytes that would result in germinal vesicle breakdown (GVB)
      stimulation and completion of meiosis without significant cytoplasmic
      abnormalities. As described above for OA, continual exposure of macaque oocytes
      to 50 nM calyculin-a (CL-A) significantly enhanced GVB at 24 h compared to that
      in controls, and the majority of the treated oocytes displayed cytoplasmic
      abnormalities. However, transient exposure (10 min) of rhesus macaque oocytes to
      either 50 nM CL-A or 1.0 microM OA enhanced GVB rates compared to that in
      controls and did not increase the incidence of cytoplasmic abnormalities. Meiotic
      maturation from germinal vesicle-intact oocytes to MII was enhanced following
      transient treatment with CL-A or OA compared to that in controls; however,
      development from MI to MII occurred at a similar frequency. In vitro-matured
      oocytes transiently exposed to OA and CL-A were capable of fertilization. In
      addition, ovarian immunohistochemical analysis revealed that both PP1 and PP2A
      were present in macaque oocytes. PP1 was localized throughout the cytoplasm with
      a predominance in the nucleus, whereas PP2A was evenly distributed throughout the
      cytoplasm with a reduction in the nuclear area. These results taken together
      differential developmental responses to inhibitor treatment and intracellular
      enzyme localizations-may be indicative of multiple regulatory roles of PP1 and/or
      PP2A during meiosis.

PMID- 9546717
TI  - Characterization of a ribonucleic acid transcript from the brook trout
      (Salvelinus fontinalis) ovary with structural similarities to mammalian
      adipsin/complement factor D and tissue kallikrein, and the effects of kallikrein
      like serine proteases on follicle contraction.
AB  - A 2.4-kilobase (kb) clone (kallikrein trout #14; KT-14) was isolated from a brook
      trout ovulatory cDNA library. KT-14 contains an open reading frame (ORF) of 768
      base pairs (bp), presumably encoding a protein of 255 amino acids. The KT-14 cDNA
      also contains a 711 -bp 5' untranslated region and a 793-bp region downstream of
      the ORF that includes a 66-bp sequence repeated 12 times. The amino acid sequence
      of the KT-14 ORF is 41 % identical to that of porcine complement factor D and 33%
      identical to that of porcine pancreatic kallikrein. On Northern blots of ovarian
      tissue, KT-14 hybridized with four transcripts of 1.8, 2.4, 2.9, and 3.2 kb.
      While the 3.2- and 2.4-kb transcripts were present in the ovary prior to meiotic
      maturation, they were significantly up-regulated at ovulation and at 12 h
      postovulation, respectively. Antibodies constructed against the recombinant KT-14
      protein recognized one 30-kDa immunogenic protein in ovarian tissue and fluid.
      This immunogenic protein was significantly elevated in the tissue by ovulation.
      Using a follicle weight loss bioassay, we provide indirect evidence that
      mammalian kallikrein and related serine proteases can stimulate brook trout
      follicle contraction. Thus, one possible function of the KT-14 protein may be the
      regulation of oocyte expulsion at ovulation.

PMID- 9546718
TI  - Pregnancy and interferon-tau induce conjugation of bovine ubiquitin cross
      reactive protein to cytosolic uterine proteins.
AB  - Conceptus-derived interferon-tau (IFN-tau) induces bovine endometrial ubiquitin
      cross-reactive protein (UCRP) mRNA and protein on Days 15-21 of pregnancy. Bovine
      UCRP retains the Leu-Arg-Gly-Gly C-terminal sequence of ubiquitin that ligates to
      and directs degradation of cytosolic proteins. The objectives of the present
      experiments were to determine whether UCRP became conjugated to endometrial
      cytosolic proteins during early pregnancy and in response to recombinant bovine
      (rbo) IFN-tau. Ubiquitin (8 kDa), UCRP (17 kDa), and conjugates thereof (> or =
      30 kDa) were quantitated using Western blotting and densitometry. Endometrial
      ubiquitin and its conjugates did not differ between Day 18 pregnant and
      nonpregnant cows, or between control and rboIFN-tau-treated (25 nM) explant
      cultures (Day 14; nonpregnant). Bovine UCRP was induced in endometrium from
      pregnant as compared with nonpregnant cows. Conjugation of endometrial proteins
      to UCRP was induced in pregnant as compared to nonpregnant cows. Recombinant
      boIFN-tau induced UCRP and its conjugates in cultured endometrial explants from
      nonpregnant cows. It is concluded that UCRP, in response to rboIFN-tau, becomes
      conjugated to endometrial cytosolic proteins during early pregnancy. The
      regulation of uterine proteins by UCRP may be integral to the maintenance of
      early pregnancy in ruminants.

PMID- 9546719
TI  - Development of Meishan and Yorkshire littermate conceptuses in either a Meishan
      or Yorkshire uterine environment to day 90 of gestation and to term.
AB  - To investigate the impacts of uterine type and conceptus genotype on development
      through late gestation, Meishan and Yorkshire embryos were co-transferred into
      the uteri of either Meishan or Yorkshire recipients that were subsequently
      slaughtered on Day 90 of gestation. At slaughter, regardless of conceptus
      genotype, fetuses and placentae were markedly smaller when recovered from Meishan
      than from Yorkshire recipients. Whereas Meishan and Yorkshire fetuses recovered
      from Meishan uteri were similar in weight, Meishan fetuses were markedly lighter
      than littermate Yorkshire fetuses when recovered from Yorkshire uteri. Because of
      the marked differences between fetal weights observed in Yorkshire recipients on
      Day 90 of gestation, Meishan and Yorkshire embryos were co-transferred to
      Yorkshire recipients that were allowed to farrow. Surprisingly, Meishan and
      Yorkshire fetuses cogestated in Yorkshire recipients were born at similar
      weights, whereas Meishan placentae were markedly smaller. The weight of Meishan
      placentae were similar on Day 90 and at term, whereas the weight of Yorkshire
      placentae were markedly larger (approximately 70%) at term than on Day 90. The
      constant weight of Meishan placentae from Day 90 to farrowing appears to result
      from an ability to increase their vascularity during this interval. In contrast,
      Yorkshire placentae may be forced to increase their weight to keep pace with
      fetal growth during this period. Because uterine capacity sets the upper limit on
      litter size, the decreased endometrial surface area required per conceptus in the
      Meishan pig seems to explain its greater potential for increased litter size.

PMID- 9546720
TI  - Uterine environment and breed effects on erythropoiesis and liver protein
      secretion in late embryonic and early fetal swine.
AB  - In this study we investigated erythropoiesis and fetal liver protein secretion
      during late embryonic (Day 24 and Day 30) and early fetal (Day 40) development in
      pigs from domestic white crossbred (WC) gilts with a normal (intact; INT) or
      crowded (unilateral hysterectomized/ovariectomized; UHO) uterine environment, or
      from prolific Chinese Meishan (MS) gilts. Increased fetal weight, fetal liver
      weight, placental weight, total red blood cells, hematocrit, blood hemoglobin
      content, and maternal plasma erythropoietin (EPO) levels were observed as
      gestation advanced. Cultured fetal liver secretion of transferrin and a protein
      of Mr 12500 and pI 7.5 also increased as gestation advanced. Fetal plasma EPO
      declined between Day 30 and Day 40. Differential counts of circulating erythroid
      precursors revealed a decline in basophilic erythroblasts and polychromatic
      erythroblasts between Day 24 and Day 40, an increase in orthochromatic
      erythroblasts on Day 30 followed by a drop on Day 40, and an increase in the
      percentage of reticulocytes/ erythrocytes from < 1.0% to approximately 90% of
      circulating red blood cells between Day 24 and Day 40. Differences among the
      treatment groups included a lower fetal survival percentage in UHO (vs. INT or
      MS) on Day 40, and higher maternal hematocrits, fetal weights, fetal hematocrits,
      fetal EPO levels, and liver transferrin secretion in WC vs. MS pigs. MS pigs had
      a lower percentage of polychromatic erythroblasts overall and a higher percentage
      of orthochromatic erythroblasts on Day 24 followed by a higher percentage of
      erythrocytes on Day 40 than WC pigs, suggesting a more mature erythron
      (circulating red blood cells plus erythropoietic tissue) in the MS pigs.
      Covariate analysis indicated that MS had larger placentae per unit of body weight
      than did WC. Conclusions were that 1) Days 24-40 of gestation is a critical time
      for fetal erythropoiesis in pigs as well as survival in a crowded uterine
      environment, 2) the MS breed may differ in the development of the fetal
      erythropoietic system because of altered fetal or uterine physiology, and 3) the
      UHO procedure did not significantly affect erythropoiesis in the fetuses studied
      but did alter fetal survival and the relationship between fetal weight and both
      hematocrit and hemoglobin on Day 40.

PMID- 9546721
TI  - Expression and immunolocalization of functional cytochrome P450 aromatase in
      mature rat testicular cells.
AB  - Aromatase activity has been measured in Leydig cells and Sertoli cells from both
      immature and mature rats. Cytochrome P450 aromatase (P450arom) has been
      immunolocalized in germ cells of the rodent, bear, and rooster. Our purpose was
      to investigate expression of and to immunolocalize P450arom in adult rat
      testicular cells. After Western blotting with a specific anti-cytochrome P450arom
      antibody, we demonstrated the presence of a 55-kDa protein in mature rat
      seminiferous tubules and crude germ cell preparations. Immunoreactive aromatase
      was detected both in cultured rat Leydig cells and in testis sections
      (interstitial tissue and elongated spermatids showed positive immunoreactivity
      for P450arom). We next used reverse transcription-polymerase chain reaction to
      localize and quantify the P450arom mRNA in the various testicular cells. In rat
      Leydig cells, the amount of P450arom mRNA was 15 times higher than in Sertoli
      cells (34.1+/-3.2 to 2.3 +/-0.2 x 10(-3) amol/10(6) cells, respectively). In
      pachytene spermatocytes, round spermatids, and testicular spermatozoa the
      P450arom mRNA levels were 38.7+/-8.1, 20.4+/-3.8, and < 1.3 x 10(-3) amol/10(6)
      cells, respectively. The aromatase activity was 2.5-4 times higher in testicular
      spermatozoa (8.48+/-1.98 fmol/10(6) cells per hour) than in other germ cells.
      These results indicate that in mature rats, not only Leydig cells and Sertoli
      cells but also germ cells have the capacity to express functional P450arom.
      According to the germ cell maturation state, there was an inverse relationship
      between P450arom mRNA content and the biological activity of the protein. The
      expression of the functional P450arom in mature rat germ cells confirms the
      existence of an additional source of estrogens within the genital tract of the
      male.

PMID- 9546722
TI  - Immunoregulatory activity in adult rat testicular interstitial fluid: roles of
      interleukin-1 and transforming growth factor beta.
AB  - Studies on the effect of rat testicular interstitial fluid (IF) on T-cell
      function have reported both stimulatory and inhibitory actions. Specific
      cytokines produced within the testis, particularly interleukin-1 (IL-1) and
      transforming growth factor beta (TGFbeta), may contribute to these apparently
      conflicting observations. In proliferation assays employing lectin- or antibody
      activated thymocytes or mature T cells in vitro, adult rat testicular IF
      stimulated T-cell activation and/or proliferation at low assay doses and was
      inhibitory at higher doses. The stimulatory activity was blocked by recombinant
      IL-1 receptor antagonist. The inhibitory activity was not affected by a
      polyspecific TGFbeta antiserum. The biological characteristics of the inhibitor
      were distinct from those of a similar, but considerably less potent, activity in
      platelet-depleted serum. These data demonstrate that rat testicular IF contains
      biologically significant concentrations of IL-1 but has a predominantly
      inhibitory action on T-cell responses. The factor predominantly responsible for
      this inhibitory activity displays a relatively large apparent molecular weight,
      is protease sensitive and partially heat labile, but does not appear to be one of
      the known mammalian TGFbeta isoforms.

PMID- 9546723
TI  - Immunoregulatory activity in adult rat testicular interstitial fluid:
      relationship with intratesticular CD8+ lymphocytes following treatment with
      ethane dimethane sulfonate and testosterone implants.
AB  - Regulation of T-cell traffic and function in the adult rat testis was assessed
      following treatment with the specific Leydig cell cytoxin, ethane dimethane
      sulfonate (EDS), and s.c. testosterone implants to prevent Leydig cell recovery.
      The distribution of T-cell subsets in the testis was determined
      immunohistochemically using stereological techniques. Testicular T cell
      inhibiting activity in the interstitial fluid was measured using a
      phytohemagglutinin-activated rat thymocyte proliferation bioassay. The mostly
      cytotoxic CD8+ T-cell subset predominated over the CD4+ (regulatory) T-cell
      subset in the normal rat testis. Destruction of the Leydig cells caused a rapid
      preferential increase in testicular CD4+ T cells, which was followed by an
      increase in both the CD8+ subset and T cell-inhibiting activity in the Leydig
      cell-deficient testis. After Leydig cell recovery, there was a significant shift
      toward the CD8+ T-cell subset in the EDS-treated testis but not in the EDS
      treated/testosterone-implanted testis. Total T-cell numbers and inhibitory
      activity in the testis returned to control levels regardless of whether the
      Leydig cells were allowed to recover. The level of inhibitory activity was
      closely related to the number of CD8+ T cells in the testis across all
      experimental groups, but it showed no relationship with pituitary hormones,
      macrophage numbers, or intratesticular testosterone levels. The data suggest that
      1) cytotoxic lymphocytes have a potentially significant role in testicular
      function and 2) T cell-inhibiting activity in the testis interstitium is not
      substantially affected by changes in pituitary hormones or Leydig cell function,
      but appears to be related to local changes in immune activity.

PMID- 9546724
TI  - Characterization of lymphocytes in the adult rat testis by flow cytometry:
      effects of activin and transforming growth factor beta on lymphocyte subsets in
      vitro.
AB  - The rat testis is considered to be an immunologically privileged site because of
      its reduced capacity to support antigen-specific immune responses. To understand
      this phenomenon, it is essential to characterize both the lymphocyte
      subpopulations normally present in the testis and their regulation by testicular
      cytokines. Peripheral blood was obtained from adult male Dark Agouti or Sprague
      Dawley rats, and testicular interstitial tissue was collected after perfusion of
      the testes to remove blood. Blood and testis lymphocytes were isolated using
      discontinuous Percoll density gradients, and the testicular lymphocytes were
      further purified by selective adherence to remove mononuclear phagocytes. The
      isolated lymphocytes were analyzed by flow cytometry using specific monoclonal
      antibodies and fluorescein labeling and were enumerated as total T cells, CD4+ T
      cells, CD8+ T cells, B cells, and natural killer (NK) cells. In contrast to
      peripheral blood, in which the CD4+ T-cell subset was the major lymphocyte
      subset, rat testis T cells were predominantly of the CD8+ subset, and a large
      population of NK cells also were present. Subsequently, peripheral blood
      lymphocytes were stimulated with the polyclonal T-cell activator,
      phytohemagglutinin, and cultured in the presence of activin, inhibin, or
      transforming growth factor beta (TGFbeta) prior to flow cytometric analysis.
      Activin and TGFbeta suppressed T-cell proliferation without any selective effect
      on either T-cell subset, and inhibin had no effect. The predominance of CD8+ T
      cells and NK cells, and the relatively minor proportion of CD4+ T cells, are
      consistent with both increased cellular immune surveillance and a reduced
      capacity for initiating antigen-specific immune responses in the adult rat
      testis.

PMID- 9546725
TI  - Developmental consequences of karyokinesis without cytokinesis during the first
      mitotic cell cycle of bovine parthenotes.
AB  - Bovine parthenogenetic embryos and bovine embryos produced by in vitro
      fertilization were compared for chromosomal complement and developmental
      potential. Oocytes (n = 1885) were matured in vitro, fertilized (n = 1151) or
      activated (n = 734) by exposure to 5 microM ionomycin for 4 min, and then treated
      with 1.9 mM 6-dimethylaminopurine for 5 h to inhibit protein kinase functions and
      promote mitosis. Mean cleavage rates at 48 h were 76.3+/-4.7% for fertilization
      and 60.1+/-4.2% for activation (p < 0.05). A similar percentage of embryos had
      reached the blastocyst stage on Day 8 post fertilization/postactivation (16.4+/
      3.3%) and (15.8+/-1.0%), respectively. Blastocysts (n = 53) produced by in vitro
      fertilization had higher total cell numbers (116.9+/-5.5) than parthenotes (n =
      71, 67.2+/-3.5 cells, p < 0.05). Differential staining indicated a significant
      reduction in the number of blastomeres allocated to both the inner cell mass and
      trophectodermal lineages in parthenotes (p < 0.05). All parthenotes (n = 65) were
      polyploid or mixoploid, with observed karyotypes of 4n (61.53%), 2n/4n (30.76%),
      2n/8n (4.61%), and 3n (3.07%). In contrast, only 9 control blastocysts (n = 53)
      revealed abnormal metaphases (16.9%). At 6 h postactivation (hpa), 70.7% of
      parthenotes (n = 65) demonstrated a fully formed pronucleus; and at 10 hpa (n =
      86), 89% had completed pronuclear formation. Pronuclear DNA replication was
      observed by 6 hpa and resulted in the formation of a second pronucleus in 76.9%
      of activated oocytes (n = 104) by 24 hpa. These pronuclear kinetics lead to a
      high number of embryos with binucleate blastomeres upon cleavage. Thus,
      alterations in the DNA content (ploidy) of bovine parthenogenetic blastocysts
      reflect ongoing karyokinesis without cytokinesis during the first mitotic cell
      cycle after exposure to a protein kinase inhibitor.

PMID- 9546726
TI  - Spatial and temporal patterns of expression of cellular retinol-binding protein
      and cellular retinoic acid-binding proteins in rat uterus during early pregnancy.
AB  - Retinoic acid, perhaps the most potent hormonal form of the naturally occurring
      retinoids (retinol and derivatives), is required in vivo for the maintenance of
      normal pregnancy and embryo development. However, little is known about the
      specific sites of action and metabolism in the uterus during pregnancy. In this
      study we describe the pattern of temporal and cell-specific expression of
      cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding
      proteins type I and type II (CRABP and CRABP[II], respectively) in the rat uterus
      during the periimplantation period (Day 1 to Day 7 of pregnancy; Day 1 = presence
      of vaginal plug). Immunohistochemical studies showed that there were dramatic and
      rapid changes in expression pattern of the retinoid-binding proteins after mating
      as early as Day 1, as well as a differential expression of these proteins when
      the mesometrial side and antimesometrial side of the uterus were examined during
      the periimplantation period. CRABP(II), whose presence has been previously shown
      to correlate with retinoic acid synthesis in the uterine epithelium, was
      specifically localized to the luminal epithelium at Day 1, being stronger on the
      mesometrial side, and then fell to lower levels. CRBP was also expressed in the
      luminal epithelium on the mesometrial side at Day 1 as well as in some stromal
      cells, declining at these sites over the next several days. CRABP was localized
      to some of the stromal cells at Day 1, overlapping CRBP expression. Embryonic
      implantation was accompanied by the appearance of CRBP and CRABP(II) in the
      decidual cells. CRBP and CRABP were also present in both smooth muscle layers of
      the uterus. The changes in the temporal and cell-specific distribution of
      retinoid-binding proteins imply a multifunctional role of vitamin A in uterine
      cell proliferation, differentiation, and embryonic implantation. The presence of
      CRABP(II) suggests that local generation of retinoic acid is important in these
      processes.

PMID- 9546727
TI  - Morphine inhibits nocturnal oxytocin secretion and uterine contractions in the
      pregnant baboon.
AB  - Morphine is a potent inhibitor of nocturnal uterine contractions (UCs) in the
      pregnant baboon, and these contractions are known to be induced by oxytocin (OT).
      The purpose of this study was to determine the mode of action of morphine in
      inhibiting nocturnal UCs by examining the effect of morphine on OT secretion, OT
      clearance, and uterine responsiveness to OT. A tethered pregnant baboon model
      during the last third of gestation was used for these experiments. In study 1,
      the effects of morphine or control saline on OT release and on spontaneous
      nocturnal UCs were examined. Study 2 determined the effects of morphine or
      control saline on the pharmacokinetics of OT after a bolus injection of OT. To
      exclude/include direct opiate effects on UCs, study 3 examined the responsiveness
      of the uterus to exogenous OT after morphine or control saline administration.
      Plasma OT levels were analyzed by RIA after extraction. UCs were assessed by
      frequency, amplitude, duration, and area under the curve. During nocturnal UCs,
      morphine, but not saline, administration resulted in the precipitous suppression
      of integrated OT levels (p < 0.05) to 42% of pretreatment values at 0-15 min
      postinjection and 17% at 30-45 min. Simultaneously, UCs were significantly
      suppressed (p < 0.05) by 75% at the 30- to 45-min interval. By 1 h, 5 of 7
      animals showed no UCs. In study 2, morphine consistently increased the metabolic
      clearance rate (MCR) of OT in all trials (p < 0.05), although the magnitude of
      this effect was small (median 9%). Finally, study 3 demonstrated that myometrial
      responsiveness to the challenge of exogenous OT was not depressed by opiate
      administration (p > 0.05). To summarize, the decrease in nocturnal UCs after
      morphine is primarily due to an inhibition of OT release, and perhaps, but to a
      much lesser extent, an increase in OT MCR. There was no evidence of a direct
      tocolytic effect of morphine on the uterus. In conclusion, opioids such as
      morphine are potent inhibitors of nocturnal UCs and act by suppressing OT release
      in the pregnant baboon.

PMID- 9546728
TI  - Relaxin inhibits the pulsatile release of oxytocin but increases basal
      concentrations of hormone in lactating rats.
AB  - The effects of porcine relaxin were examined in urethane-anesthetized, lactating
      rats to clarify the actions of relaxin on basal levels and the pulsatile release
      of oxytocin during suckling. Baseline plasma oxytocin concentrations were 27.6+/
      2.9 pM in unsuckled rats. They were significantly increased in rats after the
      onset of suckling (34.5+/-2.4 pM) compared with unsuckled animals. Oxytocin
      concentrations were increased further during reflex milk ejection (41.2+/-2.7
      pM). Treatment with porcine relaxin (5 microg in 0.1 ml saline) caused a
      significant (p < 0.05) increase in plasma oxytocin compared with pretreatment
      concentrations or saline injection in all three groups. Frequent blood samples
      were taken before and during milk ejection to confirm pulsatile oxytocin
      associated with reflex milk ejection. Short-lived (5-10-sec) pulses with peak
      concentrations of oxytocin 392.4+/-122.1 pM were observed shortly before or at
      the time of the peak rise in intramammary pressure associated with reflex milk
      ejection. Relaxin (5 microg i.v.) completely suppressed the pulsatile release of
      oxytocin. These data suggest that relaxin increases basal secretion of oxytocin
      but inhibits the pulsatile secretion associated with reflex milk ejection.

PMID- 9546729
TI  - Functional studies of human decidua in spontaneous early pregnancy loss: effect
      of soluble factors and purified CD56+ lymphocytes on killing of natural killer-
      and lymphokine-activated killer-sensitive targets.
AB  - Inappropriate leukocyte activation and disturbance of the delicate cytokine
      balance within the uterus during early human pregnancy may initiate spontaneous
      abortion. The purpose of the present study was to assess whether decidual soluble
      factors from women suffering sporadic spontaneous early pregnancy loss could
      enhance the cytotoxic activity of peripheral blood lymphocytes (PBL), and to
      investigate the lytic activity of endometrial granulated lymphocytes (eGL)
      purified from decidua against natural killer (NK)- and lymphokine-activated
      killer (LAK)-sensitive targets. Decidual cell culture supernatants from sporadic
      spontaneous abortion cases did not have any effect on PBL cytotoxic activity
      against the NK-sensitive target cells K562. Endometrial GL purified from decidua
      of spontaneous aborters were unable to lyse the LAK-sensitive target cells Raji
      and, in contrast with eGL from decidua of first-trimester therapeutic aborters,
      approximately 50% of the cases also failed to kill K562 cells. These results do
      not provide evidence to implicate either cell-mediated or cytokine-mediated
      cytolytic mechanisms in early spontaneous pregnancy loss, thus strengthening the
      possibility that other damaging effects are operating. Nevertheless, the
      deficient cytotoxic activity in a proportion of spontaneous abortion decidua
      merits further investigation.

PMID- 9546730
TI  - Endometriotic lesions synthesize and secrete a haptoglobin-like protein.
AB  - To explore the identity and possible function of endometriosis protein-I (ENDO
      I), which is an acidic glycoprotein synthesized and secreted by endometriotic
      lesions, partial amino acid sequence and cDNA sequence were determined. Partially
      purified, de novo-synthesized rat endometriosis glycoproteins were separated by
      two-dimensional SDS-PAGE, transferred to polyvinyl difluoride membranes, and
      stained with Coomassie blue. Protein corresponding to the size and pI of ENDO-I
      was cut from the membranes and analyzed by automated Edman degradation. ENDO-I
      amino acid sequence analysis identified 15 residues that shared significant
      homology with the beta-chain of rat, mouse, and human haptoglobin (Hp) and human
      Hp-related protein. Western blot analyses using anti-Hp antibody demonstrated
      cross-reactivity with de novo-synthesized ENDO-I protein in endometriosis culture
      media. For nucleotide sequence analysis, poly A-enriched mRNA was isolated from
      rat endometriotic tissues. A gene-specific oligonucleotide primer was designed
      and used for 3' rapid amplification of cDNA ends (RACE). Automated sequencing of
      RACE cDNA fragments identified 859 base pairs, of which 858 were identical to rat
      Hp. Reverse transcription-polymerase chain reaction was used to demonstrate that
      ENDO-I transcripts are differentially expressed by endometriosis but not by
      uterine tissues. In the human, distinct subtypes of Hp as well as proteins
      sharing epitopes with Hp have been used to diagnose a variety of diseases;
      therefore, Hp-like ENDO-I may prove to be a nonsurgical diagnostic tool to assess
      endometriosis. Hepatic Hp, induced by acute-phase stimuli, modulates macrophage
      function and angiogenic activity. If ENDO-I possesses similar activities, it may
      be involved with anomalies of the immune system or the etiology and
      pathophysiology of endometriosis.

PMID- 9546732
TI  - Expression of intercellular adhesion molecule-1 messenger ribonucleic acid and
      protein in human term placental cells and its modulation by pro-inflammatory
      cytokines (interleukin-1beta and tumor necrosis factor alpha).
AB  - Intercellular adhesion molecule-1 (ICAM-1) is a ligand for the integrins
      lymphocyte function-associated antigen-1 (LFA-1) and complement receptor-3 (Mac
      1), making it an important participant in many immune and inflammatory processes.
      Previous studies suggested that lack or reduced expression of ICAM-1 on
      trophoblast might partially explain its resistance to lysis by cytotoxic
      effectors. However, whether or not the adhesion molecule is expressed on
      placental cells is still a matter of debate. In this study, we determined ICAM-1
      expression at mRNA, surface, and soluble protein levels on human trophoblasts
      throughout their functional differentiation in culture from cytotrophoblasts into
      syncytiotrophoblasts. Placental cells were obtained from 6 term placentas derived
      from normal pregnancies. ICAM-1 mRNA was detected by reverse transcription
      polymerase chain reaction using two oligonucleotide primers specific for the
      human ICAM-1 gene. A single major DNA band of the expected size (943 base pairs)
      was obtained in both cytotrophoblasts and syncytiotrophoblasts. Flow cytometric
      analysis demonstrated expression of surface ICAM-1 protein on 45.5+/-3.5% of
      cytotrophoblasts. No changes were observed during differentiation in culture.
      Levels of the soluble form of ICAM-1 (sICAM-1) released by placental cells were
      undetectable when assessed by a specific ELISA. Finally, we investigated the
      effect of pro-inflammatory cytokines on placental ICAM-1 expression. Treatment of
      cultured trophoblasts for 24 h with interleukin-1beta (1 ng/ml) or tumor necrosis
      factor alpha (1 ng/ml) increased surface expression of ICAM-1 without inducing
      sICAM-1 shedding. However, on placental cells, the two cytokines exerted
      stimulatory effects lower than those detected on endometrial cells used as
      positive control. These observations document that the ICAM-1 gene is expressed
      in both cytotrophoblasts and syncytiotrophoblasts, suggesting that the molecule
      may be of value for some immune-mediated processes. On the other hand, the low
      sensitivity of trophoblasts to cytokine-mediated induction of ICAM-1 expression
      might represent a functional mechanism contributing to maternal tolerance for
      fetal graft.

PMID- 9546731
TI  - Apoptosis, bcl-2 expression, and proliferative activity in human endometrial
      stroma and endometrial granulated lymphocytes.
AB  - Human endometrial leukocytes undergo regular cyclical changes during the
      menstrual cycle, with a striking increase in the phenotypically unusual
      population of CD56+ CD16- endometrial granulated lymphocytes (eGLs) in the late
      secretory phase and early pregnancy. The factors that regulate this increase in
      eGL numbers are unclear; their unusual morphology, however, has led to the
      suggestion that they undergo apoptosis at the end of the menstrual cycle.
      Apoptosis, bcl-2 expression, and proliferative activity were examined in the
      stroma of normal cycling, progesterone-treated, and early-pregnancy endometrium.
      The expression of bcl-2 and the Ki67 proliferation marker by highly purified (>
      98% CD56+) eGLs from endometrium during the menstrual cycle and from first
      trimester decidua was also studied. Apoptotic cells were rarely observed in the
      endometrial stroma of any of the samples examined. Stromal bcl-2 expression,
      however, increased from the proliferative to the premenstrual phase, and double
      immunohistochemical labeling demonstrated large numbers of bcl-2+ CD56+ eGLs. In
      contrast, Ki67 expression was high in the endometrial stroma during the
      proliferative phase, fell during the secretory phase, and rose again
      premenstrually, because of expression by eGLs. Isolated CD56+ eGLs also showed
      high bcl-2 and Ki67 expression at the end of the menstrual cycle. Unlike
      premenstrual endometrium, progesterone-treated endometrium and first-trimester
      decidua contained few proliferating cells, expressed high levels of bcl-2, and
      showed no evidence of apoptosis. Thus, eGLs do not undergo apoptosis in
      premenstrual endometrium, and their regulatory mechanisms remain to be clarified.

PMID- 9546733
TI  - Ovary-independent estrogen receptor expression in neonatal porcine endometrium.
AB  - Effects of age and ovariectomy (OVX) at birth on uterine growth, endometrial
      development, and estrogen receptor (ER) expression were determined for intact and
      OVX gilts (n = 5 per day) hysterectomized on postnatal days (PND) 0, 15, 30, 60,
      90, or 120. Uteri were evaluated histologically, and ER protein and mRNA
      expression were characterized immunohistochemically and by in situ hybridization.
      OVX did not affect uterine weight or endometrial thickness until after PND 60,
      when both increased more rapidly in intact gilts. Neither did it affect genesis
      of uterine glands, which were present and which proliferated after PND 0, or
      endometrial ER expression patterns in glandular epithelium (GE), luminal
      epithelium (LE), or stroma (S) between PND 0 and 120. Endometrium was ER negative
      at birth. On PND 15, the ER signal was strong in GE, weak in S, and effectively
      absent in LE. Thereafter, although the ER signal remained strong in GE and
      increased through PND 60 in S, it was not evident consistently until after PND 30
      in LE. The data indicate that 1) porcine uterine growth and endometrial
      morphogenesis are ovary-independent processes before PND 60; 2) uterine gland
      genesis is associated temporally with development of ER-positive endometrial GE
      and S; and 3) regulation of endometrial ER expression is ovary independent
      between PND 0 and 120. The results establish the ER as a marker of GE
      differentiation and implicate this receptor in mechanisms regulating endometrial
      morphogenesis in the neonatal pig.

PMID- 9546734
TI  - Regulation of anion secretion by prostaglandin E2 in the mouse endometrial
      epithelium.
AB  - The present study was an investigation of the regulation of anion secretion
      across cultured mouse endometrial epithelium by prostaglandin E2 (PGE2) using the
      short-circuit current (ISC) technique. The cultured endometrial monolayers
      responded to both apical and basolateral application of PGE2 with a sustained
      rise in ISC in a concentration-dependent manner. However, the potencies of apical
      and basolateral addition of PGE2 were different, with apparent EC50 of 200 and 4
      nM, respectively. Replacement of Cl- or HCO3- in the bathing solution
      significantly reduced the ISC responses to both apical and basolateral addition
      of PGE2; however, the apical response exhibited greater dependence on HCO3- .
      Pretreatment with diphenylamine 2,2'-dicarboxylic acid, a Cl- channel blocker,
      significantly reduced both PGE2-induced ISC responses, while pretreatment with
      amiloride, a Na+ channel blocker, did not exert any effect. Forskolin, an
      adenylate cyclase activator, and 3-isobutyl-dihydro-testosterone-1-methyl
      xanthine, a cAMP phosphodiesterase inhibitor, mimicked the ISC response to PGE2
      while MDL12330A, an adenylate cyclase inhibitor, completely abolished the PGE2
      induced ISC. The results of the present study indicate that the anion secretion
      across the mouse endometrial epithelium may be regulated by PGE2 involving a cAMP
      dependent mechanism predominantly. The differential responses to apical and
      basolateral challenge with PGE2 also suggest that PGE2 of different origins may
      play different roles in uterine function.

PMID- 9546735
TI  - Intrauterine infusion of high doses of pig trophoblast interferons has no
      antiluteolytic effect in cyclic gilts.
AB  - In the pig species, the preimplanting trophoblast is known to synthesize and
      secrete high amounts of interferon during early development. Previous experiments
      in cyclic gilts using total conceptus secretory proteins suggested that porcine
      trophoblastic interferons, unlike those of ruminants, exert no effect on the
      luteal cycle. In the present experiment, cyclic Meishan gilts were divided into
      two groups, cannulated on both uterine horns, and given daily injections of
      either a placebo or increasing doses of a mixture of recombinant interferon-gamma
      and interferon-delta, on Days 11-14 of the estrous cycle. In treated gilts, the
      injected doses were much higher than those previously found in uterine perfusates
      from pregnant gilts. However, no significant differences could be found between
      the control (n = 4) and the treated (n = 5) group concerning the days of the
      estrous cycle for mid-decrease of progesterone (control: Day 14.5+/-0.57 [mean+/
      SD]; treated: Day 15+/-1.25), the day of estrus (control: Day 19+/-0.96; treated:
      Day 19.6+/-0.55), and the subsequent ovulation rate (control: 14+/-2.2 corpora
      lutea; treated: 13.1+/-1.1 corpora lutea). These data confirm that pig
      trophoblastic interferons, unlike those of ruminants, do not themselves exert an
      antiluteolytic effect. A possible synergistic effect of embryonic estrogens on
      the luteal functions of nonpregnant sows remains to be determined.

PMID- 9546736
TI  - Prostaglandin F2alpha-induced luteolysis of aging corpora lutea in
      hysterectomized pigs.
AB  - Prostaglandins primarily of uterine origin play an important role in parturition.
      Hysterectomy of nongravid pigs early in the luteal phase maintains luteal
      function until about Day 150, whereas the duration of normal pregnancy is about
      114 days. A precisely timed peak release of relaxin and coincident decrease in
      progesterone secretion in unmated hysterectomized gilts are similar to hormonal
      changes that occur a few hours before parturition. It is hypothesized that
      prostaglandin F2alpha (PGF2alpha) in hysterectomized pigs mimics abrupt changes
      in ovarian and pituitary hormone secretion seen before normal parturition and in
      early lactation. Unmated Yorkshire gilts were hysterectomized on Days 6-8 of a
      normal estrous cycle, and at 1200 h on Day 113, they were given an i.m. injection
      of 30 mg PGF2alpha-trihydroxymethylaminomethane (THAM) salt or PBS. None of these
      gilts expressed behavioral estrus immediately after PGF2alpha or vehicle
      treatment. On Day 113, PGF2alpha increased peak relaxin (60 ng/ml) compared with
      that of controls (34 ng/ml; p < 0.01), whereas progesterone decreased abruptly (4
      vs. 16 ng/ml in PGF2alpha and PBS; p < 0.01). Prolactin remained at < 5 ng/ml
      from Day 98 to 120 in controls but peaked at 33 ng/ml immediately after PGF2alpha
      treatment on Day 113, and then decreased to levels similar to those of controls
      on Day 120. Sequential bleeding revealed an acute growth hormone release (4.5
      ng/ml) immediately after PGF2alpha injection and return to basal levels (< 0.6
      ng/ml) on Days 114-120. PGF2alpha induced abrupt shifts in progesterone, relaxin,
      prolactin, and growth hormone secretion in hysterectomized gilts that mimicked
      hormone changes seen in late pregnancy, parturition, and early lactation. These
      findings provide new insight into the role of PGF2alpha in abruptly changing
      hormone secretions by aging corpora lutea and the pituitary gland even in the
      absence of conceptuses or the uterus in the pig.

PMID- 9546737
TI  - Effects of dialyzing gamma-aminobutyric acid receptor antagonists into the medial
      preoptic and arcuate ventromedial region on luteinizing hormone release in male
      sheep.
AB  - We investigated the effects of microdialyzing alpha-aminobutyric acid (GABA)
      receptor antagonists into either the medial preoptic area (mPOA) or the arcuate
      ventromedial region (ARC-VMR) on LH secretion. Bicuculline methiodide (BMI,
      GABA(A) receptor antagonist), and either 2-hydroxysaclofen (SAC) or CGP 55845A
      (CGP, GABA(B) receptor antagonists) were used. In experiment 1, castrated rams
      received 4-h dialysis into either the mPOA (n = 5) or ARC-VMR (n = 4) of
      artificial cerebrospinal fluid (aCSF) followed by 4 h of either BMI (aCSF-BMI,
      375 microM in mPOA, 1 mM in the ARC-VMR for 2-1/2 h), or aCSF-SAC (5 mM). In
      experiment 2, castrated rams received dialysis only in the ARC-VMR (n = 5) of
      aCSF-aCSF, aCSF-BMI (375 microM), or aCSF-CGP (50 microM). In experiment 3,
      untreated or testosterone (T)-treated castrated rams (n = 6/group) received
      dialysis only in the ARC-VMR of aCSF-aCSF, aCSF-BMI (375 microM), or aCSF-CGP
      (500 microM). Jugular blood was collected at 10-min intervals. In experiment 1,
      BMI suppressed mean plasma LH (p < 0.05) and increased interpulse interval (IPI,
      p < 0.05) at both sites. In experiment 2, BMI significantly reduced mean LH and
      increased IPI (p < 0.01). In experiment 3, BMI reduced mean LH in both the
      presence (p < 0.05) and absence of T (p < 0.01) and increased IPI (p < 0.01) in
      the absence of T. SAC, CGP, and aCSF did not affect LH in any experiment. These
      results show that dialysis of BMI, into either the mPOA or the ARC-VMR of either
      castrated or T-treated castrated rams decreased LH release, whereas dialysis of
      GABA(B) antagonists at these sites was without detectable effect.

PMID- 9546738
TI  - Identification of cigarette smoke components that alter functioning of hamster
      (Mesocricetus auratus) oviducts in vitro.
AB  - Previous studies have shown that solutions of mainstream and sidestream cigarette
      smoke decrease both ciliary beat frequency and oocyte cumulus complex pick-up
      rate of hamster oviducts in vitro. The purpose of this study was to identify the
      component(s) in smoke that produces these effects. Chemicals reported to be
      ciliotoxic in other systems were tested on hamster infundibula at various
      concentrations to determine whether a dose-response inhibition of ciliary beat
      frequency occurred. In addition, the concentration of each test component was
      measured in mainstream and sidestream smoke solutions (whole, particulate, and
      gas phase). All test components (acrolein, formaldehyde, phenol, acetaldehyde,
      and potassium cyanide [KCN]) inhibited ciliary beat frequency in a dose-dependent
      manner. Inhibition of ciliary beat frequency was at least partially reversible
      for all test compounds except acrolein. The concentrations of acrolein,
      formaldehyde, and phenol that were required to inhibit beat frequency were at
      least 3-50 times higher than their corresponding concentrations in smoke
      solutions. In contrast, cyanide was present in all smoke solutions at
      concentrations sufficient to inhibit ciliary beat frequency. Cilia on the outer
      surface of the infundibulum function in picking up the oocyte cumulus complex.
      Oocyte cumulus complex pick-up rate was measured in vitro at KCN concentrations
      shown to inhibit ciliary beat frequency. Pick-up rate was likewise inhibited by
      KCN and remained significantly depressed after washout of KCN. These data show
      that cyanide is a potent inhibitor of both ciliary beat frequency and oocyte
      cumulus complex pick-up rate and that its concentration in smoke solutions is
      sufficiently high to explain the previously reported inhibition of these
      oviductal processes.

PMID- 9546739
TI  - Metabolism of pyruvate by the early human embryo.
AB  - Pyruvate is added to all media used for human in vitro fertilization and embryo
      culture, but its function(s) in the early embryo is unknown. We tested the
      possibility that pyruvate can act as an oxidizable energy source by measuring the
      consumption of pyruvate and oxygen by Day 2 and Day 3 human embryos, using
      microfluorometric techniques. Oxygen consumption (19.6 pmol/embryo per hour)
      could account for the oxidation of only 56% of the pyruvate consumed (13.9
      pmol/embryo per hour). Oxygen was also consumed in the absence of exogenous
      substrates. Lactate appeared in the incubation medium with pyruvate (0.47 mM) as
      sole exogenous substrate at a rate of 12.1 pmol/embryo per hour, at a similar
      rate (10.85 pmol/embryo per hour) in the presence of 1 mM glucose and 0.47 mM
      pyruvate, and at 2.25 pmol/embryo per hour in the absence of exogenous
      substrates, suggesting that a high proportion of the pyruvate taken up by early
      human embryos is converted to lactate. Pyruvate uptake in the presence of UK5099,
      a pyruvate transport inhibitor, was reduced to 10% of control values, consistent
      with the presence of the monocarboxylate carrier in the human embryo plasma
      membrane.

PMID- 9546740
TI  - Molecular cloning and characterization of P47, a novel boar sperm-associated zona
      pellucida-binding protein homologous to a family of mammalian secretory proteins.
AB  - P47, a peripherally associated 47-kDa protein of porcine spermatozoa, was
      identified by affinity chromatography in the fraction of solubilized plasma
      membrane proteins bound to immobilized porcine zona pellucida glycoproteins. N
      terminal and internal amino acid sequences revealed structural similarity between
      P47 and rat O-acetyl ganglioside synthase, bovine mammary gland protein
      (MGP)57/53 and mouse milk fat globule protein E8-polypeptides of unknown function
      secreted by mammary gland epithelial cells in both species. A polyclonal antibody
      directed against bovine MGP57/53 displayed cross-reactivity with P47. Indirect
      immunofluorescence analysis located porcine P47 on the acrosomal cap of
      testicular sperm and on sperm recovered along different sections of the ductus
      epididymidis, as well as on swim-up and in vitro-capacitated sperm. Porcine P47
      was demonstrated on sperm bound to the zona pellucida of a homologous oocyte.
      Western blot analysis identified P47 (or MGP57/53) homologous proteins in porcine
      and human milk. Like the sperm-associated protein, porcine milk P47 possesses
      affinity for isolated, biotinylated sow oocyte zona pellucida glycoproteins.
      Reverse transcription-polymerase chain reaction was used to isolate P47
      homologous cDNAs from porcine testis and mammary gland tissues as well as from
      bovine, mouse, and human testis. P47 proteins deduced from these cDNA sequences
      showed 60-100% amino acid sequence identity. These proteins display a mosaic
      structure organized into two N-terminal, tandemly arranged epidermal growth
      factor (EGF)-like domains followed by a region with similarity to C1 and C2
      domains found in blood clotting factors V and VII. The second EGF-like domain
      contains an arginine-glycine-aspartic acid sequence, a motif often found in
      integrin receptor ligands. P47-like proteins are not expressed solely in
      testicular and mammary gland tissues. Northern blot analysis showed that P47 mRNA
      is transcribed in several porcine and bovine tissues. These data indicate a
      potential role for boar sperm-associated P47 in membrane remodeling and/or as a
      zona pellucida binding protein.

PMID- 9546741
TI  - Fetal and maternal endocrine changes approaching parturition in the goat: lack of
      evidence for prostaglandins E2 and F2alpha as signals for luteolysis.
AB  - We investigated the temporal relationship of fetal cortisol secretion to
      circulating concentrations of fetal ACTH1-39 and its high-molecular weight
      precursors in goats. We also measured the concentrations of progesterone,
      estradiol-17beta estrone sulfate, prostaglandin (PG) E, PGF2alpha, and PGF2alpha
      metabolite (PGFM) in maternal arterial plasma over the last month of gestation.
      Prostaglandin concentrations were also measured in utero-ovarian venous plasma.
      There was a positive association between ACTH1-39 in fetal plasma and the
      prepartum surge in fetal cortisol that commenced 8 days before labor. The fetal
      cortisol surge was followed by a simultaneous decrease in maternal progesterone
      and an increase in plasma estrogens commencing 3-4 days before labor. No change
      in basal prostaglandin concentration occurred before this time. There was a
      positive veno-arterial difference of PGE and PGF2alpha across the uterine
      vascular bed, confirming the uteroplacental unit as a major source of these
      eicosanoids in the plasma of the pregnant doe. We conclude that the fetal signal
      for parturition precedes luteolysis by some 5 days and find no evidence of
      changes in the basal concentrations of PGE and PGF2alpha in maternal plasma at
      the time of luteolysis.

PMID- 9546742
TI  - Cryopreservation and orthotopic transplantation of mouse ovaries: new approach in
      gamete banking.
AB  - Mouse half ovaries were cryopreserved and orthotopically transplanted into
      ovariectomized recipients genetically identical to ovary donors except for the
      coat color gene. Fertility was reestablished in 57% of the female recipients,
      which became pregnant in an average of 40 days after transplantation of frozen
      thawed half ovaries. These experiments demonstrate that ovary cryopreservation
      can be a very useful option for banking mouse germplasm, or managing subfertile
      animal colonies, when embryo or sperm freezing cannot be used or is not cost
      effective.

PMID- 9546743
TI  - Complementary expression of HIP, a cell-surface heparan sulfate binding protein,
      and perlecan at the human fetal-maternal interface.
AB  - The human hemochorial placenta is a structure formed by the invasion of
      cytotrophoblasts into the uterus. Previous studies from our laboratory have
      demonstrated a role for heparan sulfate proteoglycans (HSPGs) and their binding
      proteins in interactions between human trophoblastic and uterine cell lines in
      vitro. In this study, expression of both mRNA and protein of a novel, cell
      surface, heparin/heparan sulfate interacting protein (HIP), by human
      trophoblastic cell lines-i.e., JAR, JEG, and BeWo-and by human cytotrophoblast
      was examined throughout gestation. Immunohistochemistry of the human fetal
      maternal interface demonstrated abundant HIP expression in cytotrophoblast cells,
      with lesser staining in syncytiotrophoblast and little or no staining in
      surrounding stromal or decidual cells. Staining with antibodies to the basement
      membrane HSPG, perlecan, demonstrated a pattern of staining complementary to that
      of HIP. Cytotrophoblasts in the uterine stroma, not affiliated with attached
      villi, displayed a less intense deposition of perlecan. In vitro binding studies
      of 125I-perlecan to a 17-amino acid synthetic peptide sequence of HIP, which has
      a high affinity and specificity for heparin/heparan sulfate, indicates that
      perlecan binds to the HIP peptide with high affinity (KDapp = 0.6 nM) and in a
      heparin-inhibitable manner. Furthermore, HIP antibodies inhibited by 61-88% in
      vitro invasion by trophoblasts in assays using primary cultures of normal human
      cytotrophoblasts. Consistent with this was the observation that
      immunohistochemically detectable HIP expression was greatly reduced in pre
      eclamptic cytotrophoblasts, a condition in which trophoblast invasion is
      abnormally shallow. It is suggested that HIP potentiates human cytotrophoblast
      interactions with HSPGs, in vivo, and facilitates trophoblast invasion processes.

PMID- 9546744
TI  - Meiotic induction in cumulus cell-enclosed mouse oocytes: involvement of the
      pentose phosphate pathway.
AB  - In this study we tested the hypothesis that the pentose phosphate pathway (PPP)
      participates in the meiotic induction of mouse oocytes. The electron acceptors
      methylene blue, phenazine ethosulfate (PES), and pyrroline-5-carboxylate (P5C)
      oxidize NADPH to NADP and activate the NADP-dependent enzymes of the PPP. Each of
      these compounds triggered a dose-dependent increase in meiotic maturation in
      hypoxanthine-arrested cumulus cell-enclosed oocytes during 17- to 18-h cultures.
      More than 96% of the oocytes underwent germinal vesicle breakdown (GVB) at the
      highest concentrations of P5C and PES tested (250 and 1 microM, respectively) as
      compared to only 45-52% of control oocytes. P5C was also stimulatory to denuded
      oocytes. Analysis of energy substrates in microdrop cultures revealed a 3.6-fold
      increase in glucose consumption by PES-treated oocyte-cumulus cell complexes that
      was associated with stimulation of GVB. On the other hand, 2-deoxyglucose, which
      interferes with glucose utilization, prevented the induction of maturation
      brought about by P5C. Apocynin and diphenyleneiodonium, inhibitors of NADPH
      oxidase, prevented meiotic maturation in the presence or absence of FSH.
      Gonadotropin-induced maturation was also prevented by 6-aminonicotinamide (6-AN)
      and dehydroepiandrosterone (DHEA), inhibitors of the two NADP-dependent enzymes
      of the PPP, and this was accompanied by suppression of glucose consumption.
      Phosphoribosyl-pyrophosphate (PRPP) is an important compound required in purine
      metabolism and can be formed from the end product of the oxidative arm of the
      PPP, ribose-5-phosphate. Ribose, which can be metabolized to PRPP, increased PRPP
      synthesis in complexes and induced meiotic maturation when added to hypoxanthine
      arrested cumulus cell-enclosed oocytes in glucose-free medium in both the
      presence and absence of FSH. PRPP levels within complexes were also increased by
      glucose and FSH, but were reduced by hypoxanthine, 6-AN, and DHEA. In addition,
      exogenous PRPP stimulated maturation in hypoxanthine-arrested oocytes. These
      results support the proposition that glucose metabolism through the PPP is
      important in the meiotic induction mechanism and may involve the generation of
      PRPP that acts, at least in part, through the purine metabolizing pathways.

PMID- 9546745
TI  - Silicosis in mice: effects of dose, time, and genetic strain.
AB  - Experimental silicosis allows study of the mechanisms of lung injury,
      inflammation, and fibrosis. Inbred mice are an attractive species in which to
      study these mechanisms because of recent progress in murine immunology, molecular
      biology, and genetics. We exposed mice to an aerosol of silica and examined the
      effects of exposure dose, the evolution of disease features over time, and the
      variation in responses among four inbred strains. In C3H/HeN mice incremental
      cumulative exposure doses of cristobalite silica caused increased initial lung
      dust burden 12 to 16 weeks post-exposure, progressively intense pathological
      responses, and increased total lung collagen (hydroxyproline). The
      histopathological changes and total lung collagen increased progressively over
      time after exposure. We compared the features of silicosis in four strains of
      inbred mice selected for common use or immunologic reactivity 16 weeks after
      aerosol inhalation exposure to crystalline cristobalite silica (70 mg/m3, 5
      hours/day, 12 days). C3H/HeN mice demonstrated histopathological silicotic
      lesions and enlarged intrapulmonary lymphoid tissue, and increased lung wet
      weight, bronchoalveolar lavage (BAL) recovery of macrophages, lymphocytes, and
      neutrophils, and total lung collagen (hydroxyproline). BALB/c mice developed
      slight pulmonary lesions; MRL/MpJ mice demonstrated prominent pulmonary
      infiltrates with lymphocytes; New Zealand Black mice developed extensive alveolar
      proteinaceous deposits, inflammation, and fibrosis. Our findings demonstrate
      orderly dose-time-response relationships, and a substantial variation of
      responses among inbred strains of mice. This model should prove valuable for
      future experimental interventions into the mechanisms of silicosis.

PMID- 9546746
TI  - Persistent overexpression of interleukin-1beta and tumor necrosis factor-alpha in
      murine silicosis.
AB  - The cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha
      (TNFalpha), derived from macrophages and other cells, may promote mononuclear
      cell inflammation and fibrosis in pulmonary silicosis. C3H/HeN mice were exposed
      to control air or to an aerosol of 70 mg/m3 cristobalite silica for 5 h/d for 12
      days and examined at 2 and 16 weeks after exposure. This exposure resulted in
      murine silicosis, as manifested by focal mononuclear cell accumulations, diffuse
      interstitial fibrosis, lymphoid tissue enlargement, recruitment of inflammatory
      cells into BAL fluid, and increased total lung collagen. Semiquantitative reverse
      transcription-polymerase chain reaction (RT-PCR) with designed primers and
      membrane hybridization with biotinylated cDNA probes were used to assess the
      abundance of IL-1beta and TNFalpha mRNA. In situ hybridization with digoxigenin
      labeled cDNA probes was used to localize gene expression. Persistent
      overexpression of both IL-1beta and TNFalpha were found at 2 and 16 weeks in the
      lungs of silica-exposed mice compared with air-sham control mice. IL-1beta and
      TNFalpha expression localized to individual mononuclear cells in the alveolar
      spaces, groups of cells within the aggregate lesions, and scattered mononuclear
      cells in BALT and lymphoid nodules. Thus, cells producing IL-1beta and TNFalpha
      appear to be intimately associated with the evolving lesions of silicosis, and
      the lymphoid tissue of the lung may be important in driving the pathogenesis of
      this disease.

PMID- 9546747
TI  - Effects of radiation on wound healing.
AB  - The pathological changes of radiation on wound healing in rats were observed by
      macroscopic, microscopic, and electronmicroscopic examination and detection of
      collagen types. We found that the wound healing process was obviously delayed by
      irradiation. First, the early phase inflammatory response was severely inhibited.
      In particular, the number of infiltrating macrophages and neutrophils was
      decreased, blood vessels were injured, and hemorrhage was evident. Second, the
      formation and maturation of granulation tissue were slowed down, fibroblasts were
      injured, and transcription of types and collagen mRNAs and synthesis and
      secretion of collagen were reduced. Finally, the reepithelialization process was
      delayed and the healing time was prolonged.

PMID- 9546748
TI  - Overexpression of MDM2, p53, and NCAM proteins in human radiation-induced skin
      ulcers.
AB  - Using immunohistochemistry, we studied the overexpression of MDM2, p53, and NCAM
      proteins in human radiation-induced skin ulcers. We found that the positive rate
      of overexpression of MDM2, p53, and NCAM was 36%, 8%, and 32%, respectively. The
      overexpression of MDM2 protein was mainly observed in the nuclei of fibroblasts
      in the deeper part of the ulcer; that of p53 protein was in the nuclei of the
      epidermis and in the cytoplasm of fibroblasts and endothelial cells, whereas that
      of NCAM was located in the cytoplasm of squamous epithelial cells of the
      epidermis and in fibroblasts, fibrocytes, endothelial cells, and leiomyocytes in
      the media of arteriolar walls. The overexpression of MDM2, p53, and NCAM may be
      related to the poor healing of radiation-induced skin ulcers and the cancer
      transformation.

PMID- 9546749
TI  - The changes and significance of c-kit expression in the irradiated bone marrow of
      mice.
AB  - There have been only a few studies on the expression of c-kit in bone marrow
      after radiation and radiation-induced apoptosis of hematopoietic cells. LACA mice
      were examined after irradiation with a dose of 60Co gamma-rays. Using a light
      microscope, electron microscope, and immunohistochemistry, we studied radiation
      induced apoptosis of hematopoietic cells and the expression of c-kit. We found
      that 5.5 Gy total body irradiation was a sublethal dose for LACA mice, induced
      suppression of leukocytes in blood, and of nucleated cells in bone marrow.
      Apoptosis of the hematopoietic cells occurred within 1 day after irradiation. The
      expression of c-kit was related to the recovery of hematopoiesis and played an
      important role in early hematopoiesis.

PMID- 9546750
TI  - Interleukin-3 gene expression in irradiated mouse bone marrow.
AB  - The expression of endogenous interleukin-3 (IL-3) gene in mouse bone marrow after
      whole body irradiation was assessed by immunocytochemistry, in situ hybridization
      (ISH), and in situ reverse transcription PCR (IS RT-PCR). The results showed
      obvious injury to the bone marrow followed by recovery 4 weeks after radiation.
      IL-3 protein was increased in the cytoplasm of recovering hematopoietic cells,
      especially at 21 days after radiation, while the mRNA was negative, except at 15
      days when the mRNA was weakly positive by ISH. IS RT-PCR showed that IL-3 mRNA
      was strongly positive in the cytoplasm of recovering hematopoietic cells,
      especially at 10 to 15 days after radiation. We postulate that endogenous IL-3
      gene may accelerate hematopoietic recovery in irradiated bone marrow and that IS
      RT-PCR may objectively report the regulation of IL-3 gene expression.

PMID- 9546751
TI  - Kinetic alterations of angiotensin-II and nitric oxide in radiation pulmonary
      fibrosis.
AB  - We studied the kinetic alterations of angiotensin-II (A-II) and nitric oxide (NO)
      in radiation pulmonary fibrosis (RPF) to determine the roles of these two types
      of vasoactive substances in the pathogenesis of RPF. We irradiated the right
      hemithorax of male Wistar rats with single doses of 0, 15, and 30 Gy of 60Co
      gamma rays and we examined the lung parenchyma at 1, 3, 5, and 7 months following
      the radiation. The rats were killed at the stated intervals and samples were
      obtained from the right lung. We measured types I and III procollagen mRNA by in
      situ hybridization and demonstrated the synthesis and distribution of A-II in the
      pulmonary tissue by immunohistochemistry. The formation and kinetic alterations
      of types I and III collagen were analyzed under polarized light microscope using
      Sirius Red stain. The hydroxyproline (Hyp) content was measured in the pulmonary
      tissue after digestion with HCl. A-II radiation immunoactivity (RIA) was assayed
      in pulmonary tissue homogenate. Pulmonary NO content, NO synthase (NOS), and the
      angiotensin converting enzyme (ACE) activities were also measured. Our results
      showed that types I and III collagen genes began to be expressed 1 month after
      irradiation. Type I collagen gene increased significantly, reaching its peak 3
      months after irradiation. As the irradiation dosage was increased from 15 to 30
      Gy, the type I collagen gene content increased significantly, while type III
      significantly decreased. The Hyp content increased with the passage of time after
      irradiation. Pulmonary A-II RIA increased significantly with the dose of
      irradiation and was chiefly produced by fibroblasts and macrophages in the
      interstitium, bronchiolar epithelium, and the anteriolar wall. Pulmonary NO and
      NOS activities decreased following irradiation. One month following irradiation,
      the expression of the type I collagen gene begins to increase, with a significant
      increase in both Hyp and type I collagen 3 months after irradiation. The
      histogenesis of RPF may be related to A-II. The interstitial cells, the
      bronchiolar epithelium, and the arteriolar wall can produce A-II and need not
      pass through the ACE pathway. Our results suggest that the A-II increase and NO
      decrease may have a role in the pathogenesis of RPF.

PMID- 9546752
TI  - The protective action of taurine and L-arginine in radiation pulmonary fibrosis.
AB  - Taurine has the ability to resist the action of oxygen-free radicals by
      protecting cytomembranes. L-arginine increases the nitric oxide in the organism,
      inhibiting some types of abnormal cell proliferation. We examined the actions and
      protective mechanisms of these two substances against radiation pulmonary
      fibrosis. The mRNA transcription and the distribution of pulmonary types I and
      III procollagen were measured by in situ hybridization. Type I and type III
      collagen in the interalveolar septa and the change ratio between the two types
      were assayed using Sirius Red staining and polarizing microscopy. Angiotensin
      converting enzyme (ACE), hydroxyproline (Hyp), malondialdehyde (MDA), and nitric
      oxide (NO) were measured in lung tissue after irradiation. We found that,
      following administration of taurine or arginine, the mRNA transcription of
      procollagen types I and III significantly decreased in the pulmonary tissue 3
      months after irradiation and the Hyp content was lower, especially after the
      administration of arginine. The extent of the radiation-induced decrease in ACE
      activity was markedly attenuated. As a substrate of NO production, arginine can
      significantly increase the pulmonary NO content. We conclude that the
      administration of taurine or arginine can significantly decrease the mRNA
      transcription of procollagen and the synthesis of type I collagen in the
      interalveolar septa and can decrease the Hyp content of the pulmonary tissue.
      Following irradiation, NO can attenuate the radiation-induced decrease in ACE
      activity. Our study suggests that exogenous NO and taurine significantly protect
      against radiation pulmonary injury.

PMID- 9546753
TI  - Preventive effects of selenium-enriched spiruline (SESP) on radiation
      pneumonitis.
AB  - We studied the early effects of selenium-enriched spiruline (SESP) on radiation
      induced pulmonary fibrosis using histopathology, cDNA-mRNA dot-blot
      hybridization, and a biochemical technique for quantifying the hydroxyproline
      content. We found marked lung injury in the irradiated group, whereas only slight
      hyperemia, hemorrhage, exudation, and thickness of the interalveolar wall in the
      lung in the selenium-treated group. The hydroxyproline (hyp) content in the lungs
      and the synthesis of type III collagen mRNA decreased in the SESP-treated group.
      Selenium-enriched spiruline may have a protective effect on the development of
      radiation pneumonitis.

PMID- 9546754
TI  - Dursban revisited: birth defects, U.S. Environmental Protection Agency, and
      Centers for Disease Control.

PMID- 9546755
TI  - Measurement of nasal irritant sensitivity to pulsed carbon dioxide: a pilot
      study.
AB  - Nasal irritation and associated symptoms (e.g., nasal congestion, rhinorrhea,
      sinus headache) are important air-pollution-related health complaints,
      particularly in so-called problem buildings. Individual differences in nasal
      irritant sensitivity are therefore of both clinical and regulatory interest. To
      document such differences, one must first functionally define perceptual acuity
      to airborne irritants. In an adaptation of an established sensory testing method,
      the authors used the odorless irritant carbon dioxide in an electronically
      controlled dilution apparatus to deliver brief (approximately 3 s) pulses at
      controlled levels (10%-70%, vol/vol), synchronized with the inspiratory phase of
      the respiratory cycle. Investigators who use this apparatus can use a variant of
      the forced-choice paradigm for threshold determination to document nasal irritant
      sensitivity. The authors recruited 30 adult volunteers (17 males, 13 females;
      average age = 41 y, range = 19-79 y) from a university laboratory complex and
      from the general community. Within this group, there was a skewed distribution of
      carbon dioxide thresholds (arithmetic mean = 28%, geometric mean = 27%
      [vol/vol]). In univariate analyses, geometric mean carbon dioxide thresholds
      differed significantly with respect to smoking status (36% carbon dioxide in
      smokers versus 25% in nonsmokers; p < .005), but not with respect to age, gender,
      or self-reported history of allergic rhinitis. In a multivariate analysis, gender
      also approached significance; females tended to show better perceptual acuity
      than males (p = .06). Neither self-reported "vasomotor rhinitis" symptoms nor
      self-reported symptomatic reactivity to environmental tobacco smoke predicted
      carbon dioxide thresholds. Pulsed carbon dioxide is well tolerated by subjects
      who participate in a threshold detection task; the procedure yields a potential
      endpoint with which to compare individuals (and groups) with respect to nasal
      irritant perceptual acuity. The relationship between such acuity and nasal
      physiologic reactivity-as well as the generalizability of such measures to other,
      more environmentally realistic irritants-has yet to be defined.

PMID- 9546756
TI  - Maternal exposure to exogenous nitrogen compounds and complications of pregnancy.
AB  - Increased lipid peroxidation and reduced antioxidant activity have been reported
      with pregnancy complications. Given that exogenous oxidants stimulate formation
      of lipid peroxides, the authors investigated the relationship between exposure to
      nitrogen-oxidizing species and pregnancy complications and took into account
      markers of antioxidant and oxidant status. The study sample included pregnant
      women who were from an area polluted by oxidized nitrogen compounds.
      Methemoglobin, a biomarker of individual exposure, was determined, as were
      measures of oxidant/antioxidant status, including glutathione balance and lipid
      peroxide levels. Only 10 women experienced normal pregnancies. The most common
      complications were anemia (67%), threatened abortion/premature labor (33%), and
      signs of preeclampsia (23%). Methemoglobin was elevated significantly in all
      three conditions, compared with normal pregnancies. Reduced:total glutathione
      decreased, whereas lipid peroxide levels increased. These results suggest that
      maternal exposure to environmental oxidants can increase the risk of pregnancy
      complications through stimulation of the formation of cell-damaging lipid
      peroxides and from a decrease in maternal antioxidant reserves.

PMID- 9546757
TI  - Trichloroethylene, tetrachloroethylene, nitrates, and other chemicals in well
      water in the Fresno-Clovis Metropolitan Area.
AB  - In this study, the author examined the spatial and temporal distribution of
      tetrachloroethylene, trichloroethylene, nitrate, and several other organic and
      inorganic chemicals in large community wells in the Fresno-Clovis Metropolitan
      Area and estimated the lifetime cancer risk associated with exposure to
      tetrachloroethylene and trichloroethylene. By 1992-1993, investigators found the
      industrial solvent tetrachloroethylene in 34 wells and found trichloroethylene in
      16 wells. All wells had detectable levels of nitrate. In addition, investigators
      found radon, arsenic, cadmium, iron, manganese, trihalomethanes, and several
      other volatile organic chemicals in the wells, but only radon and arsenic posed a
      significant health risk. In 1995, 16 wells were closed because chemicals were
      found in them. Twenty-six of 248 (10.5%) active wells and 24 of 43 (55.8%) closed
      wells contained multiple contaminants, excluding nitrate. Between 1988 and 1993,
      concentrations of trichloroethylene, tetrachloroethylene, and nitrates increased
      in selected wells. Daily, monthly, and bimonthly variations in the concentrations
      of tetrachloroethylene, trichloroethylene, and nitrate were often considerable.
      Granulated activated carbon filtration reduced trichloroethylene levels in well
      water by 91%-95%, and the author examined its usefulness as a remedial measure.
      Estimated lifetime cancer risks for tetrachloroethylene and trichloroethylene
      were 1 excess cancer death per 9.5 million people and 1 excess death per 250
      million, respectively. The author also included recommendations for the conduct
      of further epidemiological and environmental studies.

PMID- 9546758
TI  - Long-term follow-up after methyl chloride intoxication.
AB  - In this study, the authors investigated mortality and cancer patterns among a
      group of individuals accidentally exposed to methyl chloride 32 y earlier. This
      group of 24 persons had survived the immediate intoxication, which had occurred
      on a trawler during a fishing trip. The authors selected a reference group, which
      contained five times as many individuals as the study group, from registers of
      crews, and they controlled for age, occupation, social class, and lifestyle
      factors. The authors established a record linkage through personal identification
      numbers with the national death register and cancer register, thus securing 100%
      follow-up. The Mantel-Haenszel point estimate (M-H) was 2.2, and the 95%
      confidence interval (CI) was 1.3-3.1 for all causes of death. There was an excess
      of deaths from cardiovascular diseases (M-H = 2.1, 95% CI = 1.2-3.8). This excess
      mortality was more prominent among deckhands who had been subject to higher
      exposure; risk ratios (RRs) were elevated for all causes of death (RR = 2.5, 95%
      CI = 1.0-5.7), as well as for cardiovascular diseases (RR = 3.9, 95% CI = 1.0
      14.4). In addition, the authors noted elevated risks for all cancers (M-H = 1.5,
      95% CI = 0.3-5.6) and for lung cancer (M-H = 2.7, 95% CI = 0.1-52.6). The authors
      concluded that exposure to methyl chloride may have contributed to the risk of
      cardiovascular disease. Investigators need to conduct further studies on groups
      exposed to methyl chloride to refute or confirm this result.

PMID- 9546759
TI  - Effect of a new ventilation system on health and well-being of office workers.
AB  - Sick building syndrome is the term given to a heterogeneous constellation of
      symptoms that affects workers in modern mechanically ventilated office buildings.
      Although the cause is unknown, there is evidence that the local environment of
      the work station is an important determinant of symptoms. In this study,
      investigators examined the effect of a new, individually controlled ventilation
      system on workers' symptoms. Investigators studied two groups of workers in one
      mechanically ventilated office building: (1) a control group at whose worksite no
      intervention was made and (2) an intervention group. The intervention consisted
      of installation of a device that allowed each worker control over the ventilation
      supplied to his or her worksite. Just before, and 4 and 16 mo after installation
      of this device, workers completed self-administered questionnaires regarding
      occurrence of symptoms. The new ventilation system resulted in higher air
      velocities, more variable temperatures, and higher concentrations of airborne
      dust and fungal spores. Four months after installation, workers with the new
      ventilation system reported fewer symptoms that were (a) work-related (p < .05)
      and that were work-related and frequent (p < .05); in addition, they reported
      fewer symptoms that reduced their capacity to work (p < .01). Sixteen months
      after installation, workers with the new device reported fewer symptoms than at
      baseline (although not as significantly), and they indicated that the indoor air
      quality improved their productivity by 11%, compared with a 4% reduction of
      productivity among the control group of workers (p < .001). Investigators
      concluded that the new ventilation system, which provided the workers with
      individual control over ventilation, was associated with important and sustained
      reduction in symptoms.

PMID- 9546760
TI  - Effects of intermittent ozone exposure on peak expiratory flow and respiratory
      symptoms among asthmatic children in Mexico City.
AB  - In a panel study of Mexican children (5-13 y of age) with mild asthma, the
      authors studied the relationship between ozone exposure and the course of
      childhood asthma. Decrements in peak expiratory flow rate were associated with
      ozone, and respiratory symptoms were associated with both ozone level and ambient
      particulate matter (< 10 microm) level. After the authors adjusted for minimum
      temperature and autocorrelation in the data, they determined that an increase of
      50 ppb in a daily ozone 1-h maximum was related to an 8% increase in cough (95%
      confidence interval = 2, 15); a 24% increase in phlegm (95% confidence interval =
      13, 35); and an 11% increase in low respiratory symptoms index (95% confidence
      interval = 5, 19). The authors concluded that children with mild asthma who
      resided in the south of Mexico City were affected adversely by the high ozone
      ambient levels observed in this area.

PMID- 9546761
TI  - Effects of lead on the somatic growth of children.
AB  - Studies on the effects of lead on the somatic growth of children are limited and
      contradictory. The authors investigated the adverse effects of blood lead
      concentration on the somatic growth of primary-school-age children. In this
      study, there was a total of 522 children, aged 6-9 y, who resided in three areas
      of Greece (i.e., Loutraki, Lavrion, and Elefsina). The medical evaluation
      included medical history; physical examination; and measurements of height, head
      circumference, and chest circumference. The authors also evaluated dietary
      information, socioeconomic status, and height of parents. The authors conducted
      laboratory tests for hematological parameters and blood lead levels. The mean
      blood lead level was 12.3 microg/dl (standard deviation = 8.9 microg/dl), and
      levels ranged from 1.3 microg/dl to 51.2 microg/dl. There were negative monotonic
      relationships between growth parameters and blood lead levels, even after the
      authors allowed for confounding effects. An increase in blood lead level of 10
      microg/dl was associated with a decrease of (a) 0.33 cm in head circumference
      (95% confidence interval = 0.12, 0.55; p = .002); (b) 0.86 cm in height (95%
      confidence interval = 0.14, 1.16; p = .020); and (c) 0.40 cm in chest
      circumference (95% confidence interval = -0.22, 1.02; p = .207). These findings
      led the authors to conclude that a decrease in growth in children may be
      associated with blood lead concentrations.

PMID- 9546762
TI  - Mineral particles in bronchoalveolar lavage fluid (BALF): an attempt at designing
      a quantitative model.
AB  - The author examined by morphology, chemical composition, and crystalline
      structure, approximately 2 500 mineral particles from bronchoalveolar lavage
      fluids obtained from 25 residents of Rome. In addition, the author obtained the
      same structural data for approximately 3000 inhalable particles present in the
      atmosphere in Rome. The author constructed a model of the concentration and
      granulometry of the different types of mineral particles in bronchoalveolar
      lavage fluids, by estimating the clearance times of the different particle
      classes. The author based the model on the following: (a) data relative to the
      inhalable particulate to which involved subjects were exposed, (b) updated
      knowledge about the processes of deposition and retention of the mineral
      particulate in the human respiratory tract, and (c) the hypothesis that the
      mineral particle pattern in bronchoalveolar lavage fluid reflects the pattern of
      particulate in lung parenchyma. Finally, the author compared the model with the
      particulate pattern observed in the bronchoalveolar lavage fluid samples. Despite
      some drastic approximations, the model satisfactorily fits the data obtained from
      the experimental research on mineral particulate in bronchoalveolar lavage fluid.

PMID- 9546764
TI  - Anonymous anti-HIV agent.

PMID- 9546763
TI  - Response to the June 13, 1996, draft report of the Commission on Risk Assessment
      and Risk Management.

PMID- 9546765
TI  - Xenotransplantation--caution, but no moratorium.

PMID- 9546767
TI  - Britain establishes Academy of Medical Sciences.

PMID- 9546766
TI  - Poor reporting of oocyte apoptosis.

PMID- 9546768
TI  - IOM panel has begun NIH spending investigation.

PMID- 9546769
TI  - Letter from Shalala feeds organ feud.

PMID- 9546770
TI  - Fight to develop drug addiction therapy.

PMID- 9546772
TI  - German/US health research agreement lacks substance.

PMID- 9546771
TI  - Indian state plans compulsory HIV testing, segregation and branding.

PMID- 9546773
TI  - Tipping the scales of herpes simplex virus reactivation: the important responses
      are local.

PMID- 9546774
TI  - A serious target for laughing gas.

PMID- 9546775
TI  - Orexins and appetite: the big picture of energy homeostasis gets a little bigger.

PMID- 9546776
TI  - Microchimerism: friend or foe?

PMID- 9546777
TI  - Two strings to the bow of Ebola virus.

PMID- 9546778
TI  - Mother knows best.

PMID- 9546779
TI  - Retroviral zoonoses.

PMID- 9546780
TI  - COX-2 inhibitors for colorectal cancer.

PMID- 9546781
TI  - Monster plaques: what they tell us about Alzheimer's disease.

PMID- 9546782
TI  - Death to a blood vessel, death to a tumor.

PMID- 9546783
TI  - Enhanced immunogenicity for CD8+ T cell induction and complete protective
      efficacy of malaria DNA vaccination by boosting with modified vaccinia virus
      Ankara.
AB  - Immunization with irradiated sporozoites can protect against malaria infection
      and intensive efforts are aimed at reproducing this effect with subunit vaccines.
      A particular sequence of subunit immunization with pre-erythrocytic antigens of
      Plasmodium berghei, consisting of single dose priming with plasmid DNA followed
      by a single boost with a recombinant modified vaccinia virus Ankara (MVA)
      expressing the same antigen, induced unprecedented complete protection against P.
      berghei sporozoite challenge in two strains of mice. Protection was associated
      with very high levels of splenic peptide-specific interferon-gamma-secreting CD8+
      T cells and was abrogated when the order of immunization was reversed. DNA
      priming followed by MVA boosting may provide a general immunization regime for
      induction of high levels of CD8+ T cells.

PMID- 9546784
TI  - Identification of a human population infected with simian foamy viruses.
AB  - Studying the transmission of simian retroviruses to humans can help define the
      importance of these infections to public health. We identified a substantial
      prevalence (4/231, 1.8%) of infection with simian foamy viruses (SFV) among
      humans occupationally exposed to nonhuman primates. Evidence of SFV infection
      included seropositivity, proviral DNA detection and isolation of foamy virus. The
      infecting SFV originated from an African green monkey (one person) and baboons
      (three people). These infections have not as yet resulted in either disease or
      sexual transmission, and may represent benign endpoint infections.

PMID- 9546785
TI  - Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the
      disruption of the tumor vasculature induced by TNF and IFN-gamma.
AB  - Administration of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) to
      melanoma patients causes selective disruption of the tumor vasculature but the
      mechanism of this disruption is unknown. Here we report that exposure of human
      endothelial cells to TNF and IFN-gamma results in a reduced activation of
      integrin alphaVbeta3, an adhesion receptor that plays a key role in tumor
      angiogenesis, leading to a decreased alphaVbeta3-dependent endothelial cell
      adhesion and survival. Detachment and apoptosis of angiogenic endothelial cells
      was demonstrated in vivo in melanoma metastases of patients treated with TNF and
      IFN-gamma. These results implicate integrin alphaVbeta3 in the anti-vascular
      activity of TNF and IFN-gamma and demonstrate a new mechanism by which cytokines
      control cell adhesion.

PMID- 9546786
TI  - TNFalpha regulation of Fas ligand expression on the vascular endothelium
      modulates leukocyte extravasation.
AB  - It is generally believed that the vascular endothelium serves as an inflammatory
      barrier by providing a nonadherent surface to leukocytes. Here, we report that
      Fas ligand (FasL) is expressed on vascular endothelial cells (ECs) and that it
      may function to actively inhibit leukocyte extravasation. TNFalpha downregulates
      FasL expression with an accompanying decrease in EC cytotoxicity toward co
      cultured Fas-bearing cells. Local administration of TNFalpha to arteries
      downregulates endothelial FasL expression and induces mononuclear cell
      infiltration. Constitutive FasL expression markedly attenuates TNFalpha-induced
      cell infiltration and adherent mononuclear cells undergo apoptosis under these
      conditions. These findings suggest that endothelial FasL expression can
      negatively regulate leukocyte extravasation.

PMID- 9546787
TI  - Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV
      replication and dissemination.
AB  - The impact of antigenic stimulation on the dynamics of simian immunodeficiency
      virus (SIV) replication was studied following repeated intravenous BCG
      inoculation of a SIV infected macaque. At the site of a delayed type
      hypersensitivity reaction to purified protein derivative of M. tuberculosis, a
      distinctive SIV variant was noted, probably as a result of the infiltration of
      activated antigen-specific T cell clones as opposed to infection by blood borne
      virus in situ. The dynamics of SIV quasispecies in peripheral blood suggests
      sequential waves of viral replication, illustrating the role of antigenic
      stimulation as a driving force in viral dissemination and pathogenesis.

PMID- 9546788
TI  - Effects of a urinary factor from women in early pregnancy on HIV-1, SIV and
      associated disease.
AB  - The effects of clinical grade crude preparations of human chorionic gonadotropin
      (hCG) on Kaposi's sarcoma, HIV, SIV and hematopoiesis were examined in vitro and
      in vivo. In contrast to previous studies, we report that the antiviral activity
      of hCG associated factors is not due to the native hCG heterodimer, including its
      purified subunits or its major degradation product, the beta-core. Using gel
      permeation chromatography of the clinical grade hCG and urine concentrates from
      pregnant women, we demonstrate that an as yet unidentified hCG associated factor
      (HAF) with anti-HIV, anti-SIV, anti-KS and pro-hematopoietic activities elutes as
      two peaks corresponding to 15-30 kDa and 2-4 kDa.

PMID- 9546789
TI  - Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated
      herpesvirus.
AB  - At a position equivalent to the gene encoding the saimiri transforming protein
      (STP) of herpesvirus saimiri (HVS), Kaposi's sarcoma-associated herpesvirus
      (KSHV) contains a distinct open reading frame called K1. Although KSHV and HVS
      are related members of the rhadinovirus subgroup of gamma herpesviruses, K1 and
      STP exhibit no similarity in amino acid sequence or in structural organization.
      Since STP is required for the oncogenic potential of HVS, we investigated the
      functional consequence of K1 expression. Expression of the K1 gene in rodent
      fibroblasts produced morphologic changes and focus formation indicative of
      transformation. A recombinant herpesvirus in which the STP oncogene of HVS was
      replaced with K1, immortalized primary T lymphocytes to IL-2 independent growth
      and induced lymphoma in common marmosets. These results demonstrate the
      transforming potential of the K1 gene of KSHV.

PMID- 9546790
TI  - Novel role of human CD4 molecule identified in neurodegeneration.
AB  - The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrophages and
      acts as a key component of the cellular receptor for HIV. At baseline, hCD4
      transgenic mice expressed hCD4 on microglia, the resident mononuclear phagocytes
      of the brain, and showed no neuronal damage. Activation of brain microglia by
      peripheral immune challenges elicited neurodegeneration in hCD4 mice but not in
      nontransgenic controls. In post-mortem brain tissues from AIDS patients with
      opportunistic infections, but without typical HIV encephalitis, hCD4 expression
      correlated with neurodegeneration. We conclude that hCD4 may function as an
      important mediator of indirect neuronal damage in infectious and immune-mediated
      diseases of the central nervous system.

PMID- 9546791
TI  - Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides.
AB  - Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques
      composed of 40- and 42-amino acid beta-amyloid (Abeta) peptides, and autosomal
      dominant forms of AD appear to cause disease by promoting brain Abeta
      accumulation. Recent studies indicate that postmenopausal estrogen replacement
      therapy may prevent or delay the onset of AD. Here we present evidence that
      physiological levels of 17beta-estradiol reduce the generation of Abeta by
      neuroblastoma cells and by primary cultures of rat, mouse and human embryonic
      cerebrocortical neurons. These results suggest a mechanism by which estrogen
      replacement therapy can delay or prevent AD.

PMID- 9546792
TI  - A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due
      to deletion of exon 9 of presenilin 1.
AB  - We describe a novel variant of Alzheimer's disease (AD) in a Finnish pedigree
      with 17 affected individuals of both sexes in three generations. The disease is
      characterized by progressive dementia which is, in most cases, preceded by
      spastic paraparesis. Neuropathological investigations revealed numerous,
      distinct, large, round and eosinophilic plaques as well as neurofibrillary
      tangles and amyloid angiopathy throughout the cerebral cortex. The predominant
      plaques resembled cotton wool balls and were immunoreactive for Abeta but lacked
      a congophilic dense core or marked plaque-related neuritic pathology. Molecular
      genetic analysis revealed that the disease was caused by a deletion of exon 9
      (delta9) of the presenilin 1 (PS1) gene from the mRNA: unlike previous examples
      of the delta9 variant, the deletion was not caused by a splice acceptor site
      mutation.

PMID- 9546793
TI  - Local paracrine effects of estradiol are central to parturition in the rhesus
      monkey.
AB  - The central biochemical mechanisms involved in primate parturition are still
      unclear. Studies in both humans and nonhuman primates such as the baboon and
      rhesus monkey indicate that many factors play a part in the cascade of
      interactive positive feedforward loops that progressively promote parturition:
      changes in maternal endocrinology, a nocturnal switch in myometrial activity from
      low amplitude, infrequent contractures to high amplitude, high frequency
      contractions (see Fig. 1), dilation of the cervix and biochemical changes in the
      fetal membranes that lead to rupture. Here we demonstrate that infusion of the
      aromatase inhibitor 4-hydroxyandrostenedione (4OHA) inhibits conversion of
      androgen to estrogen and prevents premature delivery caused by administration of
      androgen to pregnant rhesus monkeys at 0.8 of pregnancy term. 4OHA also inhibited
      the androstenedione induced maternal endocrine and fetal membrane biochemical
      changes, and alteration of myometrial activity patterns. Secondly, peripheral
      estrogen infusions increased myometrial activity but did not produce preterm
      delivery or fetal membrane changes. We conclude that paracrine functions of
      estrogen at its site of production play critical and central roles in delivery in
      the non-human primate.

PMID- 9546794
TI  - Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and
      neurotoxin.
AB  - Extensive research has failed to clarify the mechanism of action of nitrous oxide
      (N2O, laughing gas), a widely used inhalational anesthetic and drug of abuse.
      Other general anesthetics are thought to act by one of two mechanisms-blockade of
      NMDA glutamate receptors or enhancement of GABAergic inhibition. Here we show
      that N2O, at anesthetically-relevant concentrations, inhibits both ionic currents
      and excitotoxic neurodegeneration mediated through NMDA receptors and, like other
      NMDA antagonists, produces neurotoxic side effects which can be prevented by
      drugs that enhance GABAergic inhibition. The favorable safety record of N2O may
      be explained by the low concentrations typically used and by the fact that it is
      usually used in combination with GABAergic anesthetics that counteract its
      neurotoxic potential.

PMID- 9546795
TI  - In vivo imaging of oligonucleotides with positron emission tomography.

PMID- 9546796
TI  - Features of the SIVmac transmembrane glycoprotein cytoplasmic domain that are
      important for Env functions.
AB  - The cytoplasmic domain (CD) of the SIVmac transmembrane protein (TM) can affect
      viral infectivity by modulating several Env functions, notably fusogenic capacity
      and incorporation into virions. In addition, envelopes with a truncated CD are
      counterselected in primary cells in culture and in vivo in rhesus macaques,
      suggesting a role for this domain in viral persistence. Here, we have used
      mutagenesis to examine specific features of the SIVmac TM CD, including the
      conserved C-terminal alpha helix and the overall length of the CD. Several
      mutations dramatically reduced and/or delayed virus infectivity in lymphoid cell
      lines. Detailed analysis of mutants revealed defects in envelope stability,
      fusogenic capacity, and virion incorporation. The primary defect associated with
      an envelope containing a 64-residue CD was rapid degradation. A mutant Env
      lacking the C-terminal alpha helix but encoding an exceptionally long CD (373
      residues) was highly fusogenic but inefficiently incorporated into virions. A
      third mutant, containing amino acid substitutions designed to alter the charge
      density of the C-terminal helix, retained cytopathic properties and showed
      enhanced fusogenic capacity but replicated with delayed kinetics. Taken together,
      these results demonstrate that CD sequence variation entails functional
      "tradeoffs" that can involve optimization of certain Env functions at the expense
      of others.

PMID- 9546797
TI  - Efficacy of fusion peptide homologs in blocking cell lysis and HIV-induced
      fusion.
AB  - Contrary to earlier reports, we have found that tri- and hexapeptides analogous
      or homologous with segments of the 23-residue N-terminal fusion sequence (FS) of
      the viral transmembrane glycoprotein gp41 (residues 517-539) did not
      significantly inhibit HIV-1-induced syncytium formation, using an uninfected cell
      infected cell fusion assay. In contrast, we found that the high molecular weight
      apolipoprotein A-1 and a 23-residue analog of the FS, with the phenylalanine
      residues at positions 524 and 527 replaced with alanine residues, were effective
      inhibitors. Although the tripeptides were ineffective as inhibitors of syncytium
      formation, we found a number of them inhibited red cell lysis induced by the
      synthetic peptide AVGIGALFLGFLGAAGSTMGARS (based on the HIV-1 gp41 FS). This
      effect was also seen with apolipoprotein A-1. The Ala524,527 analog of the fusion
      sequence could not be tested in this system because it was hemolytic. We
      concluded that the smaller peptides were effective inhibitors of hemolysis
      because they interfered with pore formation by the fusion sequence peptide,
      either by disrupting the pores or by preventing the peptide from adopting the
      alpha-helical conformation found in the pores. On the other hand, membrane
      fusion, which is a prelude to syncytium formation, has been shown to require the
      fusion sequence in the beta-strand conformation. We argue that small peptides
      would be unable to block interaction between such strands, although larger
      molecules, such as apolipoprotein A-1 and the Ala524,527 analog, would be able to
      do so and thus inhibit fusion. It seems, therefore, that a successful drug
      directed against the FS-cell membrane interaction stage of syncytium formation
      would need to be of relatively high molecular weight and complexity.

PMID- 9546798
TI  - Administration of recombinant human interleukin 12 to chronically SIVmac-infected
      rhesus monkeys.
AB  - With the demonstration that interleukin 12 can enhance natural killer (NK) cell
      activity and drive CD4+ lymphocytes toward T helper type 1 (Thl) responses, there
      is a strong rationale for exploring the use of this cytokine as an
      immunomodulatory therapy in HIV-1-infected individuals. To assess its potential
      safety and effects on both immune and virologic aspects of HIV-1 infection,
      recombinant human IL-12 (rhIL-12) was assessed in rhesus monkeys chronically
      infected with the simian immunodeficiency virus of macaques (SIVmac). The
      activity of rhIL-12 on rhesus monkey lymphocytes was confirmed with the
      demonstration that peripheral blood lymphocyte lysis of the NK-sensitive cell
      line Colo was enhanced by this recombinant cytokine. Further, rhIL-12 was shown
      to induce interferon-gamma production by rhesus monkey lymphocytes in vitro.
      Then, in separate studies, two treatment regimens of rhIL-12 were assessed in
      SIVmac-infected monkeys: a low-dose regimen (0.1 microg/kg, daily for 4 weeks)
      and a high-dose regimen (2.5 microg/kg, every 3-4 days, for 3 weeks). Both rhIL
      12 treatment regimens were well tolerated by these virus-infected animals. The
      high-dose regimen of rhIL-12 induced transient decreases in circulating
      lymphocytes in the SIVmac-infected monkeys. Furthermore, no changes in lymphocyte
      associated SIVmac DNA or SIVmac plasma RNA levels were seen in the treated
      monkeys. These studies indicate that short-term treatment with rhIL-12 is well
      tolerated and causes no measurable changes in virus load in chronically SIVmac
      infected rhesus monkeys.

PMID- 9546799
TI  - An experimental prime-boost regimen leading to HIV type 1-specific mucosal and
      systemic immunity in BALB/c mice.
AB  - Induction of mucosal as well as systemic immunity to HIV-1 is considered to have
      high priority in current concepts of future AIDS vaccines. Here we show that the
      desired immune responses can be elicited by an experimental prime-boost regimen
      consisting of mucosal (intragastric) application of a recombinant vaccinia virus
      carrying the HIV-1 env gene (vSC25), followed by parenteral (intradermal)
      immunization with the recombinant HIV-1 glycoprotein 160 (rgp160). Following
      intragastric immunization of mice with vSC25 in combination with the mucosal
      adjuvant cholera toxin (CT), HIV-1 env-specific IgA was secreted by B cells of
      Peyer's patches and the lamina propria. Moreover, mucosal (intragastric and
      intranasal) application of vSC25 (both in presence or absence of CT) induced a
      long-lasting, HIV-1 env-specific systemic cytotoxic T cell response. Subsequent
      intradermal boosters with rgp160 led to HIV-1-specific T cell memory and serum
      antibodies.

PMID- 9546800
TI  - Immunoliposomes containing antibodies to costimulatory molecules as adjuvants for
      HIV subunit vaccines.
AB  - Immunoliposomes containing monoclonal antibodies (MAbs) to the costimulatory
      molecules CD28 and CTLA4 and their counterreceptors B7-1 (CD80) and B7-2 (CD86)
      were evaluated for the ability to increase the immune response to recombinant
      envelope protein rgp120 of the MN strain of human immunodeficiency virus type 1
      (HIV-1) during vaccination. MAbs were attached to rgp120-containing liposomes via
      a biotin-avidin-biotin bridge. Mice vaccinated with immunoliposomes were found to
      have a strong delayed-type hypersensitivity (DTH) response to the weakly
      immunogenic gp120 that was dependent on the presence of the MAbs. However, this
      vaccination protocol did not induce humoral immunity. The DTH response was not
      accompanied by increased production of interferon gamma (IFN-gamma) or
      interleukin 4 (IL-4), implying that the primary cellular interaction was between
      the immunoliposomes and cells of the reticuloendothelial system and not helper T
      (Th) cells. This strategy of incorporating antibodies to costimulatory molecules
      on the surface of antigen-containing particulates, such as liposomes or
      microspheres, can be used to increase DTH immune responses to protein or peptide
      vaccines.

PMID- 9546801
TI  - Immunologic cross-reaction between HIV type 1 p17 and Mycoplasma hyorhinis
      variable lipoprotein.
AB  - Monoclonal antibodies directed against the HIV-1 matrix protein p17 that react
      with a component present on the surface of HIV-1-infected cells have previously
      been described. In this study we show that one of these monoclonal antibodies
      binds to persistently HIV-1-infected cell lines that are coinfected with
      Mycoplasma hyorhinis, but not to cell lines that are uninfected with mycoplasma.
      Mycoplasma-infected cells secrete HIV-1 at a higher rate, have a slight increase
      in cell surface expression of gp120 and gp41, and are less sensitive to
      immunotoxins than uninfected cells. The anti-p17 antibody binds to a protein of
      M. hyorhinis grown in cell-free culture. The variable expression and size of the
      protein among strains is typical of the variable lipoprotein (Vlp) system of M.
      hyorhinis. Confirmation of the reactivity of the antibody with a Vlp was provided
      by demonstrating its specific binding to recombinant VlpF expressed in E. coli,
      and to a synthetic peptide representing the carboxy-terminal region of VlpF, but
      not to other recombinant Vlp products or peptides. This is a true cross-reaction
      because the antibody also binds to recombinant p17 expressed in E. coli and the
      binding is inhibited by the VlpF peptide. These analyses highlight the potential
      of mycoplasma contamination of tissue culture cell lines to cause anomalous
      results. With regard to HIV-1, mycoplasma infection of cells results in increased
      rates of virus secretion, and introduces a potential confounding immunologic
      cross-reaction as well. The existence of a cell surface form of p17 is unlikely.

PMID- 9546802
TI  - HIV type 1 infection of human macrophages induces an upregulation of manganese
      superoxide dismutase gene that may protect cells from death.
AB  - It has been previously demonstrated that HIV-1 infection induces a downregulation
      of MnSOD transcription in CD4+ lymphocytes. Using clinical isolates of macrophage
      tropic HIV-1 strains we report here that conversely, purified normal human
      monocyte-derived macrophages (MDMs) overexpress the manganese superoxide
      dismutase (MnSOD) gene in response to infection and viral replication. This
      upregulation of MnSOD gene expression is concomitant with tumor necrosis factor
      alpha (TNF-alpha) and interleukin 6 (IL-6) production and treatment of HIV-1
      infected MDMs with a specific transcriptional inhibitor of TNF-alpha synthesis
      counteracts the HIV-1-induced MnSOD gene activation. Moreover, TNF-alpha but not
      IL-6 addition mimicks the effects of HIV-1 infection on MnSOD gene regulation in
      normal MDM cultures. These observations strongly suggest that the MnSOD gene
      induction detected in HIV-1-infected MDMs is triggered by TNF-alpha produced in
      culture supernatants in parallel to HIV-1 particle release. In contrast to MnSOD,
      HIV-1 infection or replication in human MDMs has no effect on copper-zinc
      superoxide dismutase (Cu/ZnSOD) gene expression.

PMID- 9546803
TI  - Macrophage protection against human immunodeficiency virus or herpes simplex
      virus by red blood cell-mediated delivery of a heterodinucleotide of
      azidothymidine and acyclovir.
AB  - Human herpesvirus (HSVs) are distributed worldwide and are among the most
      frequent causes of viral infection in HIV-1-immunocompromised patients. Hence,
      therapeutic strategies able to inhibit HSV-1 and HIV-1 replication are sorely
      needed. Until now, the most common therapies against HSV-1 and HIV-1 infectivity
      have been based on the administration of nucleoside analogs; however, to be
      active, these antiviral drugs must be converted to their triphosphorylated
      derivatives by viral and/or cellular kinases. At the cellular level, the main
      problems involved in the use of such drugs are their limited phosphorylation in
      some cells (e.g., antiretroviral drugs in macrophages) and the cytotoxic side
      effects of nucleoside analog triphosphates. To overcome these limitations, a new
      heterodinucleotide (AZTp2ACV) consisting of both an antiretroviral and an
      antiherpetic drug, bound by a pyrophosphate bridge, was designed and synthesized.
      The impermeant AZTp2ACV was encapsulated into autologous erythrocytes modified to
      increase their recognition and phagocytosis by human macrophages. Once inside
      macrophages, metabolic activation of the drug occurred. The addition of AZTp2ACV
      loaded erythrocytes to human macrophages provided effective and almost complete
      in vitro protection from HIV-1 and HSV-1 replications, respectively. Therefore,
      AZTp2ACV acts as an efficient antiviral prodrug following selective targeting to
      macrophages by means of loaded erythrocytes.

PMID- 9546804
TI  - Phenotypic variability of lymphocyte populations in peripheral blood and lymph
      nodes from HIV-infected individuals and the impact of antiretroviral therapy.
      DATRI 003 Study Group. Division of AIDS Treatment Research Initiative.
AB  - This study presents immunophenotypic variation in lymphocyte populations obtained
      from peripheral blood and lymph nodes from individuals with early HIV disease who
      were enrolled in a prospective, open-label study. At baseline, there was a
      significantly greater percentage of B cells and significantly smaller percentage
      of CD8+ cells in lymph nodes compared with peripheral blood. Evaluation of
      lymphocyte phenotypic markers of function, maturation, and activation at baseline
      revealed a significantly higher percentage of activated CD4+ cells in lymph nodes
      compared with peripheral blood, whereas the percentages of activated CD8+ cells
      were similar in both compartments. After an 8-week period of randomly assigned
      treatment, peripheral blood phenotypic marker changes included (1) a reduced
      proportion of activated cells (HLA-DR+) in antiretroviral-naive patients who
      received zidovudine (ZDV), and (2) as increased proportion of "naive" cells
      (CD45RA+) in individuals, previously administered ZDV alone, who received ZDV and
      didanosine (ddI) therapy. The lymph node phenotypic marker analysis showed no
      significant changes over the 8-week treatment period. Overall, the study
      demonstrates significant differences in lymphocyte subsets from lymph nodes
      compared with peripheral blood and suggests that further studies be performed to
      determine the functional significance of these phenotypic subsets.

PMID- 9546805
TI  - Failure to quantify viral load with two of the three commercial methods in a
      pregnant woman harboring an HIV type 1 subtype G strain.
AB  - The level of HIV-1 RNA in plasma has become one of the most important markers in
      the follow-up of HIV-infected patients. Three techniques are commercially
      available: both the Amplicor HIV Monitor and the NASBA HIV-1 RNA QT are target
      amplification methods, whereas the Quantiplex HIV RNA assay is a branched DNA
      signal amplification technique. Detection in both target amplification techniques
      is based on a single primer pair and a single probe in the gag region, whereas
      multiple probes capture the pol region of the viral RNA in the branched DNA
      assay. We investigated the discrepant observation of an undetectable viral load
      in an immunodeficient pregnant HIV-1-infected patient of African origin with no
      prior antiretroviral treatment. Although clinical progression was present in this
      patient with tuberculosis and a low CD4 cell count, viral load determinations
      with both the Amplicor Monitor and NASBA assays revealed no detectable RNA
      levels. The presence of HIV-1 RNA in the plasma of the patient was demonstrated
      by an in-house RNA-PCR. Subsequent HIV-1 RNA quantification with the branched DNA
      method revealed a high viremia (460,000 copies/ml). DNA sequence analysis of the
      gag gene identified a subtype G HIV-1 strain (HIV-1BL). To our knowledge this is
      the first report of a patient harboring an HIV-1 genotype of the main group with
      a high viral load as quantified by the branched DNA assay, but undetectable with
      the two commercial HIV RNA amplification techniques because of genetic
      divergence. In the case of discrepant low viral loads determined by one
      amplification technique in patients with advanced clinical stage one should use
      an alternative quantification technique for confirmation.

PMID- 9546806
TI  - Complete nef gene sequence of HIV type 1 subtype B' from professional plasma
      donors in the People's Republic of China.

PMID- 9546808
TI  - ATP-dependent transport of lipophilic cytotoxic drugs by membrane vesicles
      prepared from MRP-overexpressing HL60/ADR cells.

PMID- 9546807
TI  - HIV type 2 Vif proteins have specific conserved amino acid motifs.

PMID- 9546810
TI  - Structure and in vitro substrate specificity of the murine multidrug resistance
      associated protein.

PMID- 9546809
TI  - Cellular and in vitro transport of glutathione conjugates by MRP.

PMID- 9546811
TI  - Cytokine profiles of in vivo activated thyroid-infiltrating T cells cloned in the
      presence or absence of interleukin 4.
AB  - We compared Th1 and Th2 cytokines secreted by randomly selected, intrathyroidal
      CD4+ T cell clones isolated from a patient with Graves' disease using IL-4 + IL-2
      versus IL-2 alone. Prior to T cell isolation, PCR of cDNA from the intact thyroid
      tissue generated IL-4 and IL-10, but not IFN-gamma, products. As controls, IL-4,
      IFN-gamma and IL-10 cDNA was amplified from stimulated, but not unstimulated,
      PBMC. All 21 of the nine IL-2 clones and twelve IL-2 + IL-4 clones isolated from
      the thyroid tissue were CD4+. With the exception of one clone in the IL-2 group,
      all clones produced IL-10 on stimulation with anti-CD3 and phorbol-12-myristate
      13-acetate (PMA) with similar mean values for both groups. The majority of clones
      in both groups also produced IFN-gamma and IL-4 after stimulation. However, the
      IL-4:IFN-gamma ratios were significantly higher in clones isolated using IL-2 +
      IL-4 than in those isolated with IL-2 alone. Furthermore, the distribution of
      Th1, Th0 and Th2 type clones, defined by their IL-4:IFN-gamma ratios, was also
      significantly different between those isolated using IL-2 alone and those
      isolated using IL-2 + IL-4. Of note, although Th0 clones predominated in both
      groups, Th1 clones were only obtained using IL-2 alone and Th2 clones were only
      obtained with IL-2 + IL-4. In conclusion, the presence of IL-4 together with IL-2
      induces a shift away from a Th1-towards a Th2-response in T cells cloned from in
      vivo-activated thyroid-infiltrating lymphocytes. This difference in cytokine
      profile emphasizes that IL-4 is required for cloning T cells representative of a
      response involving both Th1 and Th2 cells, as occurs in autoimmune thyroid
      disease.

PMID- 9546812
TI  - Autoimmunity to ryanodine receptor and titin in myasthenia gravis is associated
      with GM allotypes.
AB  - Myasthenia gravis (MG) is mediated by autoantibodies against the acetylcholine
      receptor at the muscle endplate. Some MG patients have in addition antibodies
      (Ab) to the skeletal muscle proteins ryanodine receptor (RyR) and titin. We have
      examined GM and KM allotypes, RyR and titin Ab in 44 MG patients (37 thymoma
      patients and 7 non-thymoma, late-onset patients) and 292 non-MG controls to see
      if GM/KM allotypes associate with differences in autoantibody production. All
      patients had titin Ab, and 15 thymoma patients had also RyR Ab. The phenotype GM
      1, 2, 3 23 5, 21 was significantly increased in the patients with titin Ab
      compared with the non-MG controls (chi2 = 4.93, p < 0.05). Thymoma patients with
      RyR Ab had a higher frequency of the GM 3 23 5 phenotype compared with RyR Ab
      negative patients and controls (chi2 = 7.1, p < 0.05). KM allotypes did not
      differ between RyR Ab positive or titin Ab positive patients and controls. GM
      phenotypes may thus be associated with an autoimmune response against the muscle
      proteins titin and RyR in MG patients.

PMID- 9546813
TI  - Beta-cell rest: a strategy for the prevention of autoimmune diabetes.
AB  - An autoantigen being recognized by specific receptors is the key reaction of an
      autoimmune disease. Whereas much efforts have been made to develop
      immunosuppressive regimens which reduce the amount of effector cells, and/or
      inhibit receptor activation, surprisingly little attention has been paid to
      reduce the ligand-receptor interaction by interfering with the amount of antigen
      being presented from the target cells. In this review, we discuss clinical
      observations in autoimmune endocrine disease which illustrate that target cell
      alterations can modify the disease activity and comment on recent clinical trials
      which indicate that beta-cell rest may be beneficial to the course of human
      autoimmune diabetes mellitus.

PMID- 9546814
TI  - HLA-DR and the development of rheumatoid arthritis.
AB  - Susceptibility to develop Rheumatoid arthritis (RA) maps to a highly conserved
      amino acid motif ("the shared epitope") expressed in the third hypervariable
      region of different HLA-DRB1 alleles. This motif, namely QKRAA, QRRAA or RRRAA
      helps the development of RA by an unknown mechanism. However, it is now
      established that the shared epitope can 1. Shape the T cell repertoire. 2.
      Interact with 70 kD heat shock proteins.

PMID- 9546815
TI  - Cytokines in the evolution of Graves' ophthalmopathy.
AB  - Infiltration of the retroocular space by inflammatory cells and the accumulation
      of glycosaminoglycans are histological characteristics of Graves' ophthalmopathy.
      Various cytokines, released by infiltrating immunocompetent cells and resident
      connective tissue cells, play a pivotal role in the evolution of this disease.
      The predominant cytokines secreted by orbital T cells during the course of the
      disease may govern the activity and stage of the local autoimmune process.
      Cytokine effects of potential relevance to the pathogenesis of Graves'
      ophthalmopathy include their ability to stimulate orbital fibroblasts to
      proliferate and secrete excess quantities of glycosaminoglycans. The edema
      associated with these hydrophilic macromolecules is directly responsible for many
      of the characteristic clinical features of the disease. In addition, certain
      cytokines induce or enhance the expression on orbital fibroblasts of
      immunomodulatory proteins. We review current evidence supporting the notion that
      cytokines are central to the development and evolution of Graves' ophthalmopathy.

PMID- 9546816
TI  - Characterisation of the antibody response to the extracellular region of
      recombinant thyrotropin receptor.
AB  - Autoantibodies to the human thyrotropin receptor (TSH-R) are pathogenic in a
      number of autoimmune thyroid diseases including Graves' disease. We have
      characterised polyclonal antisera to TSH-R for antibodies which may mimic those
      present in autoimmune thyroid disease. For immunisations, recombinant
      extracellular region of human TSH-R which does not interact with its ligand TSH
      was used. The induced antibodies react with the full length membrane receptor in
      transfected mammalian cells by flow cytometry showing the presence of antibody
      capable of recognising the native functional receptor. The properties of the
      generated antibodies have been compared after two injections or following a
      multiple immunisation protocol with the receptor in adjuvant. High titre antisera
      were readily generated after the short injection protocol and further
      immunisations did not lead to any change in antibody titers. Analysis of the
      epitopes recognised using synthetic peptides confirmed previous observations that
      the immunodominant determinants localise to the amino and the carboxyl terminal
      part of the extracellular region of the receptor. Antisera from both rabbits
      contain TSH blocking antibody as assessed by inhibition of TSH mediated cAMP
      stimulation. There was an increase in TSH binding inhibitory immunoglobulin
      (TBII) activity with multiple injections. Furthermore, the increase in TBII
      activity was not related to spreading of the antibody response to new
      determinants on TSH-R. Our results support previous observations on the
      difficulties in reproducing, by adjuvant immunisation with recombinant TSH-R
      preparations, the fine specificity of antibodies to TSH-R present in autoimmune
      disorders such as Graves' disease or primary myxoedema.

PMID- 9546817
TI  - X-chromosome inactivation in monozygotic twins with systemic lupus erythematosus.
AB  - The hypothesis that a low concordance rate in monozygotic (MZ) twins with
      systemic lupus erythematosus (SLE) may be accounted for by differences in X
      chromosome inactivation was examined. Five MZ twin pairs, four discordant and one
      concordant, were recruited, zygosity confirmed by DNA fingerprinting, and their
      pattern of X-chromosome inactivation in DNA samples prepared from peripheral
      blood and buccal cells were examined. X-chromosome inactivation was assessed by
      the methylation status of the CpG region near trinucleotide repeats in exon 1 of
      the androgen receptor gene on X-chromosome after digestion with the methylation
      sensitive enzyme HpaII or HhaI and PCR amplification. X-chromosome inactivation
      patterns were found to be the same between affected and non-affected twins in all
      four discordant twin pairs, with random patterns in two pairs and skewed patterns
      in the others. The concordant twins demonstrated the same random patterns. X
      chromosome inactivation was also examined from buccal smear DNA and shown to have
      the same pattern as that noted from peripheral blood DNA in one informative twin
      pair. Differences in X-chromosome inactivation patterns were not observed in
      these five MZ twin pairs. The results could not support the hypothesis that
      differences in X-chromosome inactivation is the mechanism accounting for the low
      concordance rate noted in MZ twins with SLE.

PMID- 9546818
TI  - Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody
      profiles in Japanese mothers.
AB  - Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized
      by two major clinical manifestations: congenital heart block and cutaneous lupus
      lesions. The disease is associated with placentally transferred maternal anti
      Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations
      with maternal autoantibody responses, haplotypic and allelic distributions, along
      with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR
      RFLP results in 25 Japanese mothers of two groups defined by precipitating
      autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB
      antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes
      DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as
      individual class II alleles DRB1*1101, DRB1*08032 and DQB1*0301 showed
      significantly increased frequencies compared to those in normal controls. All
      anti-Ro/SSA and anti-La/SSB positive mothers carried DRB1 alleles that shared the
      same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These
      mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared
      the same amino acid residues at positions 27-36 and 71-77 of hypervariable
      regions of the DQB1 chain. Furthermore, all mothers with both anti-Ro/SSA and
      anti-La/SSB were homozygous for DPB1*0501. Nine of 10 anti-Ro/SSA and anti-La/SSB
      positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected
      infants. Thus, our findings suggest that there may be immunogenetic differences
      among mothers according to their autoantibody profiles, and that mothers with
      both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than
      mothers with anti-Ro/SSA alone.

PMID- 9546819
TI  - Contribution of structural neuroimaging to the early diagnosis of Alzheimer's
      disease.
AB  - There is compelling evidence for the early involvement of the hippocampal
      formation in the natural history of Alzheimer's disease (AD). The evidence comes
      from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type
      histopathologic changes limited to the hippocampus have been described and may be
      seen in normal aging subjects. The sites of maximal neuronal loss in the
      hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally
      cognitively impaired (MCI) individuals (defined by ratings of functional capacity
      and psychiatric symptomatology) exhibit a neuropsychological profile that is
      distinct from that of the unimpaired elderly. Pathologic evidence suggests that
      most of these cases already have AD brain changes accentuated in the hippocampal
      region, and our own longitudinal studies reveal that 70% of this group develop
      dementia within a 4-year period. We have developed a negative-angle axial view
      designed to cut parallel to the anterior-posterior plane of the hippocampus.
      Using this modified axial plane of section in conjunction with computed
      tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence
      of hippocampal atrophy in normal aging and across severity levels of cognitively
      impaired elderly patients. Longitudinal study shows that hippocampal atrophy is a
      sensitive and specific predictor of future AD for patients with MCI. MRI volume
      study of AD patients, controls, and MCI patients shows specific hippocampal
      volume loss in MCI. We conclude that the atrophic changes associated with early
      AD can be visualized using qualitative techniques and are readily quantifiable
      with volumetry. This article is not intended to be comprehensive, but to provide
      an overview of some of the structural neuroimaging data from our laboratory.

PMID- 9546820
TI  - Are the hypervariable regions of S RNases sufficient for allele-specific
      recognition of pollen?

PMID- 9546821
TI  - A full genome screen for autism with evidence for linkage to a region on
      chromosome 7q. International Molecular Genetic Study of Autism Consortium.
AB  - Autism is characterized by impairments in reciprocal social interaction and
      communication, and restricted and sterotyped patterns of interests and
      activities. Developmental difficulties are apparent before 3 years of age and
      there is evidence for strong genetic influences most likely involving more than
      one susceptibility gene. A two-stage genome search for susceptibility loci in
      autism was performed on 87 affected sib pairs plus 12 non-sib affected relative
      pairs, from a total of 99 families identified by an international consortium.
      Regions on six chromosomes (4, 7, 10, 16, 19 and 22) were identified which
      generated a multipoint maximum lod score (MLS) > 1. A region on chromosome 7q was
      the most significant with an MLS of 3.55 near markers D7S530 and D7S684 in the
      subset of 56 UK affected sib-pair families, and an MLS of 2.53 in all 87 affected
      sib-pair families. An area on chromosome 16p near the telomere was the next most
      significant, with an MLS of 1.97 in the UK families, and 1.51 in all families.
      These results are an important step towards identifying genes predisposing to
      autism; establishing their general applicability requires further study.

PMID- 9546822
TI  - Proceedings of the 1997 International Symposium, Exhibit and Workshop on
      Preparative Chromatography, Ion Exchange and Adsorption/Desorption Processes and
      Related Techniques. Washington, DC, USA. 1-4 June 1997.

PMID- 9546823
TI  - Benign form of congenital angulation of long bones associated with shortening of
      soft tissues.
AB  - We report a benign form of congenital angulation of long bones associated with
      shortening of soft tissues. The patients were three males and four females
      including two siblings. The average age at first examination was 6 months (range,
      1-17 months) and that at the time of follow-up was 7 years (range, 13 months-11
      years). The characteristics were short-limb type short stature, congenital
      multiple angulation deformities of the long bones of both upper and lower
      extremities, with almost the same angulation directions for all the patients and
      improvement of the deformities with age. There was also accelerated skeletal
      maturation, lack of epi-metaphyseal lesions, skin dimples, limitation of the
      ankle joint dorsiflexion, and inconspicuousness of skin creases on the flexor
      side of the elbow and knee. This phenotype is not consistent with any of the bent
      bone dysplasia group. Caffey's report [Caffey J (1947). Am J Dis Child 74:543
      5621 included two different subtypes of bent bones, round bowing and sharp
      angulation, and the latter are similar to this report. However, Caffey's cases
      lack limitation of ankle dorsiflexion and reduced skin creases. An autosomal
      recessive mode of inheritance could be present in this subtype.

PMID- 9546824
TI  - Autosomal dominant Klippel-Feil anomaly with cleft palate.
AB  - Klippel-Feil anomaly is characterized by the fusion of two or more cervical
      vertebrae. Most cases are sporadic but dominant and recessive inheritance are
      well described. Associated anomalies such as a cleft palate are common. We
      describe a unique family with autosomal dominantly inherited Klippel-Feil anomaly
      in six individuals associated with a cleft palate in four. One patient, a child,
      has a cleft palate only but may develop radiological cervical fusion with time,
      as documented in two other family members.

PMID- 9546826
TI  - A boy with severe manifestations of type A1 brachydactyly.
AB  - We describe a male with type A1 brachydactyly, a descendant of Drinkwaters second
      family. In addition to absence of the middle phalanges of his hands and feet he
      has generalised skeletal abnormalities, nystagmus and a squint. We suggest that
      his clinical findings represent the more severe manifestations of this autosomal
      dominant gene.

PMID- 9546825
TI  - Mutation of the MITF gene in albinism-deafness syndrome (Tietz syndrome).
AB  - A mother and her son with albinism and sensorineural deafness compatible with
      Tietz syndrome (MIM 103500) are reported. An in-frame deletion of the MITF gene
      that is identical at the molecular level to the mouse mi mutant allele has been
      found in this family. MITF gene mutations account for 20% of Waardenburg syndrome
      (WS) type II. These data, together with the wide spectrum of mutant alleles
      reported in mi mice (which have pigmentary disorders), suggest that MITF could be
      regarded as a candidate gene in various pigmentation disorders in man.

PMID- 9546827
TI  - Brachydactyly type A1 with abnormal menisci and scoliosis in three generations.
AB  - We report a three-generation family in which four members had brachydactyly type
      A1, degenerative arthritis of the knee as a complication of abnormal menisci, and
      variable scoliosis. Nine of the 15 individuals in the two generations preceding
      the proband had brachydactyly. Three of these nine had degenerative arthritis of
      the knee including the proband's father who had meniscal degeneration with tears.
      One other had radiologically confirmed discoid menisci. Of those with
      brachydactyly, five also had scoliosis. Although autosomal dominant inheritance
      of brachydactyly A1 and discoid menisci have been reported separately,
      cosegregation of these features in one family has not previously been described
      and seems to comprise a unique autosomal dominant condition. The combination of
      brachydactyly, meniscal abnormalities including discoid meniscus, and scoliosis
      suggests that this disorder represents a new osteochondrodysplasia syndrome.

PMID- 9546828
TI  - Four cases of amelia of the upper limb associated with anal atresia--is this
      VACTERL with extreme limb involvement?
AB  - Amelia is an extremely rare abnormality with a highest reported incidence of 1 in
      67,500 liveborn infants. We now report four cases in each of which amelia
      involving one upper limb occurred in association with anal atresia. The pattern
      of other abnormalities present in these cases suggests that this combination of
      amelia and anal atresia falls within the spectrum of the VACTERL association.

PMID- 9546829
TI  - Cerebellar hypoplasia, facial dysmorphism and internal abnormalities: a new
      recessive syndrome?
AB  - Three female sibs had cerebellar hypoplasia, facial dysmorphism comprising a high
      forehead, lowset posteriorly rotated ears, a prominent upper lip and receding
      chin, and variable internal abnormalities. Two of the cases had deficient
      lobulation of the lungs, two had an atrial septal defect of the heart and
      developmental abnormalities of the urinary system or internal genitalia, one had
      holoprosencephaly. All had normal chromosomes. This syndrome does not seem to
      have been reported before and may be inherited in an autosomal recessive manner.

PMID- 9546830
TI  - Two sisters with growth failure, microcephaly, peculiar facies and apical
      dystrophy: the presentation of brachymorphism-onychodysplasia-dysphalangism
      syndrome?
AB  - We report two sisters with growth failure, relative microcephaly, peculiar facies
      and apical dystrophy (brachydactyly type B). They had shortness and clinodactyly
      of the 5th fingers, aplasia or hypoplasia of the distal phalanges of 5th fingers,
      short medial phalanges of the 2nd and 5th fingers, hypoplasia or aplasia of
      distal phalanges of 2-5th toes, with tiny toenails, and aplasia or nails of 5th
      fingers and right 5th toe in the younger sister. Dysmorphic facial features
      included high forehead, sparse hair, blepharophimosis, telecanthus, epicanthic
      folds, a low nasal bridge, a broad nasal tip and micrognathia. Their ears were
      low-set and malformed. The older sister additionally had a high-pitched voice and
      eczema on the face and limbs. In the younger sister a cardiac defect was
      diagnosed--ventricular and atrial septal defect, patent ductus arteriosus. They
      had some clinical features of Coffin-Siris syndrome, but with a milder phenotype
      and much less severe mental handicap. Their clinical picture resembles more the
      brachymorphism-onychodysplasia-dysphalangism (BOD) syndrome.

PMID- 9546831
TI  - Unusual association of congenital malformations: craniosynostosis, heart defect,
      abnormal intestinal innervation and urogenital abnormalities.
AB  - Monozygotic male twins and an unrelated boy are described who have an unusual
      association of malformations, i.e. craniosynostosis of the sagittal suture, a
      cardiac malformation, urogenital anomalies, intestinal malformations and a single
      umbilical artery. The twins are discordant for these features, except for
      Hirschsprung disease. No similar cases could be traced in literature. The
      possible genetic background is discussed.

PMID- 9546832
TI  - Oral-facial-digital (OFD) syndrome with associated features: a new syndrome or
      genetic heterogeneity and variability?
AB  - We report a male patient with clinical characteristics compatible with an OFD
      syndrome and previously unassociated findings such as myelomeningocele, stenosis
      of aqueduct of Sylvius and heart anomalies, that we feel that may represent a new
      type of OFD syndrome (XII).

PMID- 9546833
TI  - Azoospermia and segmentation abnormalities of the cervicothoracic spine ('MURCS
      in the male').
AB  - The MURCS association is traditionally regarded as a disorder limited to the
      female sex. It has been hypothesized that men displaying the combination of
      azoospermia, segmentation abnormalities of the cervicothoracic spine and renal
      anomalies may have a male analogue of MURCS. Here we describe a patient with non
      obstructive azoospermia and Klippel-Feil anomaly type II and suggest that this
      may represent another case of 'MURCS in the male'.

PMID- 9546834
TI  - Congenital ptosis and blepharophimosis in a mentally retarded girl: a new case of
      Ohdo syndrome?
AB  - A mentally retarded girl with congenital blepharophimosis, ptosis, hypoplastic
      teeth and other traits consistent with Ohdo syndrome is reported. Her mother had
      had surgery for blepharophimosis as a small child, but did not fulfil the other
      criteria for Ohdo syndrome. The mother had also been abusing alcohol prior to the
      pregnancy. Differential diagnoses and possible modes of inheritance are
      discussed.

PMID- 9546835
TI  - Re: Spondylometaphyseal dysplasia with characteristic facial appearance.

PMID- 9546836
TI  - Enchondromatosis with features of dysspondyloenchondromatosis and Maffucci
      syndrome.
AB  - We report a girl with multiple enchondromatosis, unequal leg length, short
      stature, congenital scoliosis, lymphangioma, and cutaneous hemangiomata. The
      skeletal findings were consistent with the clinical and radiological features of
      dysspondyloenchondromatosis except that short stature was not apparent in the
      neonatal period. Dysspondyloenchondromatosis is a rare disorder, one of the
      several types of multiple enchondromatosis with spinal abnormalities. In previous
      reports of this condition the association of vascular lesions usually found in
      Maffucci syndrome has not been described.

PMID- 9546838
TI  - A new case of the acromegaloid facial appearance syndrome?
AB  - An apparently new case of the acromegaloid facial appearance syndrome is
      reported. The main clinical findings were coarse facies and thickened lips, oral
      mucosa and upper eyelids. The patient also had macrocephaly with an arachnoid
      cyst in the right middle fossa, an anomaly not previously described in
      association with this syndrome.

PMID- 9546837
TI  - Livedo reticularis, developmental delay and stroke-like episode in a 7-year-old
      male.
AB  - Livedo reticularis is a vascular abnormality of the skin resulting in an
      erythematous reticular rash. The combination of livedo reticularis and stroke
      like episodes in adults is known as Sneddon syndrome [Sneddon, IB (1965). Br J
      Dermatol 77:180-188]. A similar combination of stroke-like episodes and livedo
      reticularis has been reported to occur in children [Baxter P et al. (1993). Dev
      Med Child Neuro 35:917-926]. We present here a 7-year-old male with congenital
      livedo reticularis, obesity, developmental delay, stroke-like episode,
      hypertension and cystic kidneys. We summarize our patient's findings and family
      history, and compare his disorder to other possibly related conditions.

PMID- 9546839
TI  - Waardenburg syndrome: variable phenotypic expression in monozygotic twins.

PMID- 9546840
TI  - The hand arm vibration syndrome: a review.
AB  - Since its first description over eight decades ago, the hand arm vibration
      syndrome-- vibration white finger as it was previously known--has become one of
      the most common prescribed diseases in the industrialized world. This article is
      intended to provide a broad review of existing evidence and knowledge regarding a
      disease which, for medicolegal reasons, demands attention from all medical
      personnel. Detailed discussion is presented regarding: the multifactorial
      aetiology of the syndrome; suggestions for clinical assessment, laboratory
      investigations and classification of disease severity; and strategies for the
      prevention and treatment of the syndrome.

PMID- 9546841
TI  - The antiphospholipid syndrome and vascular surgery.

PMID- 9546842
TI  - Interposition vein cuffs--are they effective?

PMID- 9546843
TI  - Patency of infrainguinal polytetrafluoroethylene bypass grafts with distal
      interposition vein cuffs.
AB  - Polytetrafluoroethylene (PTFE) prosthetic bypasses in the lower extremity have
      poor patency rates, particularly in limb salvage cases. Patency and limb salvage
      rates of PTFE bypasses supplemented by distal interposition vein cuffs were
      assessed in patients requiring revascularization for critical limb ischemia, in
      the absence of a suitable autologous saphenous vein. Between October 1993 and
      April 1996, 163 patients underwent 185 infrainguinal bypasses. Forty-three limbs
      in 42 patients (12 women, 30 men; mean age 67 years) did not have a suitable
      autologous saphenous vein (24%) and had femoropopliteal (20) and infrapopliteal
      (23) bypasses performed. Patients were examined prospectively at 3-month
      intervals during the first year and at 6-month intervals thereafter to determine
      graft patency and limb salvage. Postoperative anticoagulation with warfarin was
      used in 26 patients. Indications for operation included limb salvage in 41
      extremities (21 rest pain/ulceration or gangrene, 20 rest pain alone), and
      disabling claudication in two. Patients were followed clinically for 2-30 months
      (mean 10 months). Cumulative 2-year life-table patencies for all grafts,
      femoropopliteal and infrapopliteal bypasses were 64%, 75% and 62%, respectively.
      Previous primary patencies at the authors' institution for PTFE bypasses without
      vein cuffs were 35%, 46% and 12% for the same categories. Cumulative life-table
      limb salvage for all PTFE/vein cuff bypasses in the present series was 76%
      compared with 37% in previous PTFE bypasses without vein cuffs. Adjunctive use of
      distal interposition vein cuffs improves prosthetic graft patency, while
      producing satisfactory limb salvage. Postoperative anticoagulation did not
      influence graft patency. PTFE/vein cuff for lower-extremity revascularization
      shows good 2-year patency and is an acceptable alternate conduit in patients with
      critical limb ischemia when autologous saphenous vein is absent.

PMID- 9546844
TI  - Nondissection method for tibial bypass surgery using Esmarch's rubber bandage or
      an automatic sequential pneumatic tourniquet: long-term results.
AB  - It is suspected that operative injury to the native arteries during a vascular
      bypass procedure causes periarterial fibrosis contributing to late graft failure.
      A a nondissection method for tibial artery bypass has been developed using
      Esmarch's rubber bandage or an automatic sequential pneumatic tourniquet. This
      retrospective study examined patency and other late results in distal bypass
      operations using the nondissection method. Between June 1982 and July 1995, 78
      tibial bypasses were performed using reversed autogenous saphenous vein grafts in
      70 patients (57 men, 13 women; mean age 57.4 years). Graft patency was assessed
      angiographically. When a stenotic lesion was recognized, the graft was revised
      and considered an assisted primary patency. Primary patency rates at 1, 3, 5, and
      10 years were 82.8%, 75.3%, 63.4% and 63.4%, respectively, by life-table
      analysis. Six grafts required revision for stenosis; one involved distal
      anastomotic stenosis. As a result, assisted primary patency rates resembled
      secondary patency rates of 87.7%, 84.3%, 80.3%, and 80.3% at the same respective
      intervals. In conclusion, the nondissection method improved long-term patency by
      preventing late distal anastomotic stenosis.

PMID- 9546845
TI  - Mesenteric bypass for chronic mesenteric ischaemia.
AB  - Chronic mesenteric ischaemia is an uncommon disease that requires treatment to
      relieve the symptoms of abdominal angina and to prevent intestinal infarction.
      Over a period of 3 years, 12 patients with visceral artery stenosis or occlusion
      were referred to the authors' service and 10 underwent mesenteric bypass
      grafting. Both the coeliac and the superior mesenteric arteries were
      revascularized in four patients, and the superior mesenteric artery alone in six
      patients, using a variety of grafts and graft configurations. This was done in
      conjunction with aortic graft placement in four cases and with renal bypass in
      three. All patients survived the procedure. At a mean follow-up of 28 months, one
      patient died of myocardial infarction 42 months after surgery, while all
      survivors are symptom-free. Chronic mesenteric ischaemia can be treated safely
      and effectively. The variation in the pattern of mesenteric occlusions and the
      frequent association with aortic and renovascular disease does not allow for a
      single 'best' technical solution but requires the surgical procedure to be
      individually tailored.

PMID- 9546846
TI  - Some popliteal aneurysms are congenital.
AB  - Although the majority of popliteal aneurysms are of atherosclerotic origin and
      are discovered in patients aged more than 50, the aetiology of a small minority
      may be attributed to arterial trauma, septic disruption, Behcet's disease, a
      medial fibromuscular dysplasia, or popliteal entrapment. The aim of this study
      was to propose a possible congenital origin for popliteal aneurysms without
      evidence of any other aetiology. A retrospective review of five younger patients
      (aged 20-45 years) with seven non-atherosclerotic popliteal aneurysms was
      performed. In patient nos 1 and 2, histological examination showed that the
      arterial wall had been replaced by an abundant collagenic tissue. After
      replacement by a saphenous bypass graft, these patients did well with a follow-up
      ranging from 1 to 15 years. Patient no. 3 was not operated on because of a
      symptomless occlusion of the tibial and peroneal arteries, and remains well 10
      years later. Patients nos 4 and 5 were treated with a saphenous bypass graft. The
      last patient also had associated bilateral congenital anomalies of the division
      of the popliteal arteries. In the absence of any evidence of any classical
      aetiology, particularly fibromuscular dysplasia and popliteal entrapment, a
      congenital aetiology is proposed in aneurysms diagnosed in younger patients. The
      complex composition of the popliteal artery, being composed by an association of
      three original segments, may induce a fragility of the arterial wall that may be
      responsible for aneurysmal deterioration as well as abnormal branching or
      popliteal artery entrapment. These aneurysms are associated with the same risk of
      thrombosis as atherosclerotic aneurysms and therefore, they should be subjected
      to the same therapeutic considerations.

PMID- 9546847
TI  - Correction of total anomalous pulmonary venous connection of the cardiac type.
AB  - Surgical treatment of the cardiac type of total anomalous pulmonary venous
      connection requires special techniques. The treatment and outcome in 17
      consecutive patients who had undergone primary repairs of the cardiac type
      between 1965 and 1996 were reviewed. The median age was 3 months and median
      weight 4.2 kg. The connection was the coronary sinus in ten patients, and the
      right atrium in six. Interatrial communication was routinely augmented. The right
      atrial cavity was partitioned using a patch to direct the anomalous pulmonary
      veins into the left atrium through the atrial septal defect in the first 13
      patients. In the last four patients, the free wall flap of the right atrium was
      developed as a neoseptum. There were three early postoperative deaths during the
      early period of conventional repair. Two patients developed residual or recurrent
      diffuse obstruction in the individual lobar veins; reoperation to relieve the
      obstruction was attempted but unsuccessful. One sudden death occurred in a
      patient with occasional heart block. Ten survivors have been asymptomatic during
      follow-up, but two incomplete heart blocks and one atrial flutter were noted
      among patients who underwent conventional repair. The right atrial wall flap
      technique was not associated with any mortality or morbidity, such as arrhythmia
      and recurrent pulmonary vein stenosis during 12 to 63 months of postoperative
      obstruction. In conclusions, a flap technique using the right atrial wall appears
      to be a promising method to decrease the incidence of supraventricular
      arrhythmias and pulmonary vein drainage obstruction following repair of the
      cardiac type.

PMID- 9546848
TI  - Predicting outcome after myocardial revascularization in patients with left
      ventricular dysfunction.
AB  - In order to identify the risk factors which could predict outcome after coronary
      artery bypass grafting in patients with left ventricular dysfunction, 80
      consecutive patients with an ejection fraction < or = 30%, who underwent isolated
      coronary artery bypass grafting at the authors' centre between January 1994 and
      May 1996 were evaluated. Preoperatively, mean(s.d.) ejection fraction was
      27.1(3.8)%, 56 patients (70%) had angina, and 56(70%) were in New York Heart
      Association (NYHA) functional class III or IV. There were five operative deaths,
      with a hospital mortality rate of 6.3%. Significant risk factors for hospital
      death were NYHA class IV, preoperative ventricular arrhythmias and left
      ventricular end-diastolic volume index > 110 ml/m2. At mean follow-up of 15(7)
      (range 6-30) months, there were six late deaths, five of which were from cardiac
      causes. Actuarial survival rate at 2 years was 82(5)% and freedom from cardiac
      death 84(5)%. Risk factors for overall mortality from cardiac causes were
      preoperative grade 2 mitral regurgitation, associated with left ventricular
      dilatation, and renal dysfunction (creatininaemia > or = 180 micromol/l). At
      follow-up, mean ejection fraction was 37.5(8.4)%, and the overall functional
      status had improved: 12 patients (18%) had angina and eight (12%) were in NYHA
      class III and IV. Myocardial revascularization in patients with left ventricular
      dysfunction can be performed with acceptably low operative risk, good survival
      rate at 2 years, and functional status improvement. Patients with extensive
      ventricular dilatation, associated with significant mitral regurgitation, have a
      lower life expectancy and less functional benefits from coronary artery bypass
      grafting. These patients are better treated by cardiac transplantation.

PMID- 9546849
TI  - Na+/H+ exchange inhibition improves post-transplant myocardial compliance in 4
      hour stored donor hearts.
AB  - Na+/H+ exchange inhibitors have cardioprotective properties. The effects of the
      new Na+/H+ exchange inhibitor, HOE642 on myocardial function were assessed after
      transplantation of canine brain-dead and non-brain-dead donor hearts preserved
      for 4 h. Four groups were studied: brain-dead donors; non-brain-dead donors;
      brain-dead donors and recipients treated with HOE642 (2 mg/kg); and treated non
      brain-dead donors and recipients. Donor hearts were stored in NIH2. At the end of
      60 min reperfusion after transplantation, pressure-volume curves were
      constructed. Biopsies were analysed histologically and ultrastructurally.
      Afterwards, weaning from cardiopulmonary bypass was accomplished. HOE642 improved
      compliance in hearts from both brain-dead and non-brain-dead donors. No
      differences in myocardial water content nor in myocardial performance were
      detected. No irreversible damage was seen ultrastructurally. It is concluded that
      myocardial compliance after transplantation was improved by administration of
      HOE642. The use of this inhibitor might improve the current myocardial
      preservation technique for transplantation.

PMID- 9546850
TI  - Predictors of hospital mortality in type A aortic dissections: a retrospective
      analysis of 148 consecutive surgical patients.
AB  - Reports in the literature frequently concern miscellaneous types of dissections.
      This makes correct interpretation of data difficult. In order to assess the
      determinants of hospital mortality, the results of 148 consecutive patients over
      a 23-year period, all operated on for a type A dissection, were reviewed.
      Mean(s.d.) age was 56(13.1) years, 64% were male. An acute dissection (surgery
      within 14 days after onset of symptoms) was performed in 139 patients. Stigmata
      of the Marfan syndrome were present in 6.1% (n = 9). Peripheral vascular
      ischaemic complications were observed in 27.7%. Nowadays, diagnosis is primarily
      confirmed using transoesophageal echocardiography (75 correct diagnoses among 76
      performed). Operation consisted of repair or replacement of the ascending aorta.
      Resuspension of the aortic valve was performed in 74 patients, and arch
      replacement in 25. In 74 patients, distal repair was done under deep hypothermic
      circulatory arrest. Hospital mortality rate was 23.6% (35 patients), though
      mortality rate calculated over the period 1990-1993 was 17.4% (P = n.s.).
      Univariate analysis revealed the following variables to be statistically
      significant predictors of hospital mortality (P < 0.05): preoperative ischaemic
      complications, preoperative resuscitation, haemopericardium, postoperative
      neurological complications, rethoracotomy, renal insufficiency and intestinal
      ischaemia. Multivariate stepwise logistic regression indicated preoperative
      resuscitation, postoperative haemodialysis and postoperative neurological
      complications as the only independent predictors of hospital death. Dissections
      arising from a primary intimal tear in the descending aorta had a more favourable
      outcome (P = 0.06, odds ratio 0.1). Although hospital mortality has declined over
      the past few years, no decline was seen in operative mortality since gelatine
      resourcine-formol (GRF) glue is used as a routine. Transoesophageal
      echocardiography is the first choice in confirming diagnosis. Early operation is
      advocated, with careful haemostasis, before the development of cardiac tamponade
      or end-organ ischaemia, as the cornerstone of a successful treatment of a type A
      dissection. Reduction of neurological complications will further improve the
      results.

PMID- 9546851
TI  - Coronary bypass with arterial conduits.
AB  - To assess the efficacy of arterial revascularization 368 patients were studied
      who underwent myocardial revascularization with two or more arterial conduits
      (group M) and compared with 2092 patients in whom a single internal mammary
      artery +/- veins (group S), and to a third group in which only saphenous vein
      conduits (group V, n = 602) were used. Group M patients were younger (aged
      54.0(9.5) years; 4.1% aged > 70 years) than either group V (67.6(8.9) years,
      40.7% > 70 years, P < 0.0001) or group S patients (62.0(8.5) years, 15.7% > 70
      years, P < 0.0001). Furthermore, this cohort group had the lowest percentage of
      females (8.4%), of urgent cases (21.7%), of preoperative myocardial infarction
      (6.0%), and of redo surgery (0.8%). In contrast, patients who received only
      saphenous vein conduits had the highest proportion of female patients (29.2%), of
      urgent cases (47.4%), of preoperative myocardial infarction (16.5%), and of redo
      surgery (5.5%). By multivariate logistic regression analysis (odds ratio in
      parentheses), redo surgery (6.06, P = 0.0001), preoperative intra-aortic balloon
      pump assist (6.11, P = 0.0001), diabetes (1.97, P = 0.03), urgent surgery (1.80,
      P = 0.05), and advanced age (2.14, P = 0.01) were all predictors of operative
      mortality. In contrast, while choice of conduit appeared to influence outcome by
      univariate analysis (4.2% mortality in group V, P < 0.001), it was not found to
      be a predictor of either mortality or morbidity by regression analysis. The
      present results indicate that, in carefully selected patients, despite increased
      technical demands with longer periods of aortic occlusion and longer pump times,
      multi-arterial grafting (compared with conventional revascularization) is a safe
      and efficacious procedure. Whether or not this approach to revascularization will
      increase long-term survival and freedom from reoperation will require further
      study.

PMID- 9546852
TI  - Coronary artery bypass grafting in a patient with type II heparin associated
      thrombopenia.
AB  - Two types of heparin-associated thrombopenia can be distinguished. Patients with
      the type II condition present a particularly difficult management problem when
      they require full anticoagulation. There is no consensus about the proper
      anticoagulation management for type II patients who have to undergo
      cardiopulmonary bypass. The case is reported of a type II heparin-associated
      thrombopenia patient who underwent successful aortocoronary saphenous vein
      grafting. Sodium-danaparoid was used for anticoagulation. The anti-factor Xa
      level was kept below the value reported in the literature for patients undergoing
      cardiopulmonary bypass. No fibrin formation was observed during the time of
      cardiopulmonary bypass, nor was any severe postoperative haemorrhage seen, as is
      frequently described in the literature.

PMID- 9546853
TI  - Primary palmar hyperhidrosis presenting with unilateral symptoms: a report of two
      cases and review of the literature.
AB  - Two cases of primary palmar hyperhidrosis are presented. T2-T3 sympathetic
      ganglionectomy of the affected side completely alleviated perspiration of the
      palms, but oversweating of the contralateral palms appeared a few weeks later. A
      similar sympathetic ganglionectomy of the second side, 1 month and 1 year later,
      resulted in renewed oversweating of the palm on the first operated side within 3
      months of the second operation. During the same period, 127 other patients with
      primary palmar hyperhidrosis underwent a bilateral upper dorsal sympathectomy,
      though the condition did not recur in any of these patients. The possible
      mechanism(s) of why overperspiration of the second hand developed after the first
      sympathectomy in these two patients, and why it recurred in the first hand after
      the second operation are examined, but remain obscure.

PMID- 9546854
TI  - [VII Congress of the Spanish Society of Neuroscience. Santander, Spain, 22-26
      September 1997. Abstracts].

PMID- 9546855
TI  - [Efficacy of the meningococcal vaccine from Group C capsular polysaccharide].
AB  - BACKGROUND: This report is a systematic review of the effect intensity and
      duration of the immune response to meningococcal serogroup C vaccine. The vaccine
      safety, efficacy and effectiveness are also analyzed. METHODS: MEDLINE literature
      search in the period 1970-1996. Meningoccocal polysaccharide vaccine clinical
      trials and human prospective studies were specifically searched. Quality of the
      retrieved studies were analyzed. Information available was integrated. RESULTS:
      Group C meningoccal polysaccharide vaccine is a safe product. Its efficacy is
      over 85% among adults and children over 5 years old. 70% (CI 95%: 5-91%) under 5
      years old, and 55% among children 2-3 years old. The vaccine is not effective
      under 2 years. The duration of protective antibody levels decrease with age. The
      proportion of vaccinated children effectively protected one year after
      vaccination is low. Vaccination does not affect the immune response to ulterior
      revaccination. CONCLUSIONS: Group C meningococcal polysaccharide vaccine is
      indicated in adults and children over 2 years old to protect them from
      meningococcal disease due to group C when exposed to high risk of infection. The
      outbreaks control is the main indication for the use of this vaccine. Routine
      immunization in not outbreak situation is not recommended due to the small
      vaccine protection in children under 2 years old, the limited efficacy in
      children under 5, and the short duration of the immunity in children.

PMID- 9546857
TI  - [Mortality among young people and its impact on life expectancy in Andalusia
      during 1980-1992].
AB  - BACKGROUND: From the middle eighties, mortality in the age group 15 to 39 years
      in Andalusia has experienced an important increase; the object of this work is to
      analyse mortality in this age group, in order to discover the causes which have
      brought about this increase in mortality and to assess its impact on life
      expectancy in the eighties. METHODS: Using the mortality data and the population
      of Andalusia from 1980 to 1992, specific rates have been calculated, both for
      mortality by age and cause as well as those adjusted for age. To quantify the
      impact of the causes of death with respect to life expectancy development, the
      Pollard method was used. RESULTS: There was a relative increase in the mortality
      of Andalusian young people between the three-yearly periods 1980-1982 and 1990
      1992. The causes contributing to this increase, amongst the male population,
      were: Aids with an excess of 825 deaths, 575 in traffic accidents, 155 suicides
      and 147 deaths from drug overdoses. These same causes of death led to total
      losses of 0.46% years in the gain of life expectancy. Amongst women, on the other
      hand, the causes of death maintained relatively stable rates, with an almost
      imperceptible effect on life expectancy at birth. CONCLUSIONS: The increase in
      mortality in the 15-40 age group for causes mentioned previously, is an almost
      exclusive phenomenon amongst young Andalusian men. This produced a slow-down in
      any gain in life expectancy during the eighties.

PMID- 9546856
TI  - [Disability evaluation: Barthel's index].
AB  - In Public Health exists a growing tendency to evaluate the impact of health
      problems both on the quality of life of the persons involved as well as the use
      of health services. In this sense, the evaluation of incapacity is acquiring ever
      greater relevance. The Barthel Index is an instrument widely used to this end and
      measures the capacity of the person for the execution of ten basic activities in
      daily life, obtaining a quantitative estimation of the subject's level of
      dependency. The Barthel Index has been used, since its introduction in 1955,
      resulting in numerous versions, as well as serving as a standard of comparison
      with other scales. It is an easily applicable method, with a high level of
      reliability and validity, capable of detecting changes, easy to interpret and the
      application of which is not problematic. On the other hand, its adaptation to
      different cultural environments is almost immediate. Although it has a few
      limitations, the Barthel Index may be recommended as a selection method for
      measuring physical incapacity, both in clinical practice as well as in
      epidemiological investigation and Public Health.

PMID- 9546859
TI  - [Healthy aging and functional disability among the elderly inhabitants of the
      Canary Islands (Spain)].
AB  - BACKGROUND: Among the elderly, health is usually measured in terms of ability for
      both the Basic and Instrumental Activities of Daily Living. The objective of this
      work is to estimate the percentage of healthy elderly among the population of the
      Canary Islands (Spain) and the factors associated with functional disability in
      this older population. METHODS: We randomly sampled 411 elderly from the whole
      population of the Canary Islands, of whom 97 had died or could not be located. Of
      the 314 people approached, 29 (9.2%) denied participation. The 285 participants
      were interviewed with the Spanish version of Pfeiffer's Functional Assessment
      Inventory previously adapted and validated in our habitat. RESULTS: Up to 53% of
      the elderly (61% of males and 47% of females) were disability-free. Greater
      disability was associated with higher age, lesser education, worse subjective
      health, worse subjective vision, and worse subjective hearing. No association of
      disability with female gender and cognitive deficit was found when including age
      and education in the logistic model. CONCLUSIONS: Health status among the elderly
      in the Canaries is similar to that in developed countries. In contrast with other
      studies, we found functional ability associated with poor hearing and dissociated
      from cognitive deficit.

PMID- 9546858
TI  - [Daily mortality in the Madrid community during 1986-1991 for the group between
      45 and 64 year of age: its relationship to air temperature].
AB  - BACKGROUND: There are many types of work which relate mortality with different
      environmental factors. These focus on the general population or in the over-65
      age-group, but are relatively few in those with reference to the 45-64 age group
      in which mortality has a large economic and social impact. The object of the
      present article is to analyse the existant association between daily mortality,
      from both diverse specific causes, as well as the air temperature in this group
      in Madrid. Madrid's extreme climatic characteristics make this work of special
      interest. METHODS: The ARIMA model was used according to the Box-Jenkins
      methodology for the infiltration of the daily series of mortality regarding
      temperature. Amongst the residuals, interrelated functions were established which
      establish an association between series eliminating communal seasonal factors as
      well as determining the length of disequilibrium between thermal extremes and
      excesses in mortality. RESULTS: There is a V-shaped relationship between total
      daily mortality and temperature. The minimum mortality rate is established at a
      maximum daily temperature of 33 degrees C. Excess mortality is 0.8% for each
      degree below 33 degrees C, while that for each degree above is 3.0%. The
      functions of interrelated correlation indicate that this association is clear in
      males regarding general mortality as well as for circulatory diseases. In the
      case of high temperature the effect is immediate, while in lower temperatures we
      have to add a delay of 10-13 days. CONCLUSION: There is a significant statistical
      association between mortality and temperature extremes in people of this age
      group. Lost life expectancy indicates the extent of the problem and the need to
      implement preventative measures.

PMID- 9546860
TI  - [Seroprevalence of the infections caused by Borrelia Burgdorferi and Rickettsia
      Conorii in humans and dogs in primary health care of San Andreas del Rabanedo
      (Leon, Spain)].
AB  - BACKGROUND: Positive results in infections of borrelia burgdorferi and Rickettsia
      conorii in human and canine population is studied in order to understand the
      situation of both in humans, and at the same time discover the importance of the
      dog as an indicator of these agents among those in the Health Area of San Andres
      del Rabanedo, Leon. METHODS: A study was made of 98 human serums and 95 canine
      serums (dogs of different breeds and capabilities) as regards B. burgdorferi
      (positive results 1/128 and 1/64, respectively) and 104 human serums and 84
      canine serums as regards R. conorii (positive results at range 1/64 in both
      species) by means of indirect Immunofluorescence (IFI). RESULTS: Positivity in
      both infections was discovered in both humans and dogs. With regard to B
      burgdorferi it was higher in humans than in dogs and with regard to R. conorii it
      was higher in dogs than in humans. In humans it was 4.08% as regards B.
      burgdorferi and 1% with respect to R. conorii: in dogs it was 2.10% as regards B.
      burgdorferi and 14.28% regarding R. conorii. The highest values were discovered
      in the Spring-Summer months except in the case of B. burgdorferi in dogs. Serum
      prevalence was greater in dogs used to guard other animals (sheep) than those
      involved in hunting and security. CONCLUSIONS: The percentages of positive
      results discovered in our work, in humans as well as dogs, estimated in the
      territorial area of a geographical zone in a semi-rural Leon province, were equal
      or inferior to those discovered in other provinces, including ours. In dogs there
      were larger positive results regarding R. conorii than B. burgdorferi, which
      indicates that it is the most extended agent within our Province, as other
      authors have pointed out. The values discovered in humans as regards B.
      burgdorferi were higher than those in dogs; the existence of reactions crossed
      with other microorganisms may have influenced these results. For this reason, we
      consider it necessary to conduct more studies on the prevalence to these
      infections to obtain an appropriate epidemiological surveillance and control of
      these zoonosis, given their impact on public health.

PMID- 9546861
TI  - [The evaluation of epidemiological services related to brucellosis in the
      Autonomous Community of the Basque Country].
AB  - BACKGROUND: Spain's Epidemiologic Notifiable Disease Surveillance System (ENDSS)
      was evaluated by reference to Brucellosis, the zoonoses with greatest incidence
      countrywide and a disease that is notifiable on a case by case basis in the
      Basque Autonomous Region (BAR). METHODS: ENDSS information and the use to which
      it was put, were analysed. Active case searching was carried out via the
      Microbiologic Information System (MIS), public hospitals and the Occupational
      Disease Registry (ODR). A comparison was run between reported and search data.
      The capture-recapture method was used to compare ENDSS against hospital cases.
      RESULTS: Risks and outbreaks wee detected. Suspect cases were not reported. There
      was a 40% post-search increase in cases, i.e., 40 versus a previous figure of 24.
      Sensitivity was estimated at 60%. Predictive Value Positive could not be computed
      however. No case definition was in force. As estimated by the capture-recapture
      method, overall sensitivity for both ENDSS and hospital-based surveillance was
      84% (95% IC: 70-100). The number of cases estimated by this method was 38 +/- 8.
      CONCLUSIONS: Underreporting is in evidence and, as a consequence, sensitivity is
      low. A case definition is called for. Response time is slowed by awaiting
      confirmation before reporting. The number of cases detected through active
      searching is compatible with that calculated by the capture-recapture method
      using only two sources.

PMID- 9546862
TI  - [The evaluation of hospital management of sanitary waste in the principality of
      Asturias].
AB  - BACKGROUND: With the object of evaluating the management of sanitary waste of 12
      publicly funded Asturian hospitals, a visit was paid to the hospital services,
      particularly significant as regards the generation of waste (a total of 91
      services). The evaluated hospitals represent 75.10% of the total hospital beds in
      the Principality. METHODS: Interviews with personnel from 91 different services
      were undertaken, always by the same interviewer, and according to the rules of
      the Joint Commission of Health Care Organizations. The information obtained was
      afterwards verified by the interviewer by means of direct observation. RESULTS:
      Amongst the most relevant results, the absence of adequate containers for
      "clinical" waste in 28.5% of the services visited, stands out. Into the bargain,
      82.4% of the services classify this type of waste incorrectly. The percentage of
      incorrect classification is 1.1% for "special" waste. In large hospitals (with
      over 300 beds), 60% of the services have information on the handling of waste,
      but only 40% of these hospitals have adequate supervision over the management of
      waste by the Service of Preventive Medicine or another equivalent service.
      CONCLUSIONS: The level of incorrect classification of sanitary waste which has
      been discovered suggests that, in order to improve the intra-hospital management
      of waste, it is necessary to increase the amount of information, modify certain
      attitudes of the hospital staff and reinforce the level of supervision executed
      by the Services of Preventive Medicine.

PMID- 9546863
TI  - [The role of the sanitary authorities in the public health network in the 21st
      century].

PMID- 9546864
TI  - [Gastro-hemorrhagic Escherichia coli].
AB  - Groups of Escherichia coli enteropathogen are described, with special attention
      to Escherichia coli enterohaemorragic. Some serotypes of Escherichia coli
      verocitotoxin-producing are able to produce haemorrhagic enteritis, which can
      develop a complication with hemolityc uraemic syndrome. This complication is most
      frequent in children and has a high mortality rate. The transmission takes place
      via food and its capacity to cause epidemic outbreaks together with the
      seriousness of the complications caused by enteritys make this microorganism of
      great importance to Public Health. The epidemiology of this microorganism in
      Spain is reviewed.

PMID- 9546865
TI  - [Tobacco use disorder prevalence among hospital workers].
AB  - BACKGROUND: In Spain, as in other countries, numerous studies on tobaccoism have
      been carried out. The purpose of this survey was to evaluate the prevalence of
      tobaccoism in a representative sample of hospital employees and its association
      with age, sex, profession level and attitudes. METHODS: Following a pilot study,
      a survey was carried out amongst a representative and random sample (n = 360) of
      hospital personnel, who were asked about their attitudes towards smoking,
      classified according to age, sex and professional level. RESULTS: The total
      percentage of smokers was 36.4%, but no significant statistical differences were
      found between sex or age group. The professional levels with the highest
      percentage of smokers are ATS/DUE and clerks. 42.8% of non-smokers declared
      having smoked in the past. ATS/DUE, clerks and doctors showed the highest
      percentage. 40.5% of smokers declare that they were willing to give up smoking,
      whereas people over 50 were the most reluctant. The majority of cigarette smokers
      admitted that they smoke in the hospital. Most of them are intermediate smokers
      (10-20 cigarettes per day) and have been so for many years. The majority of
      former smokers gave up smoking in recent years. CONCLUSIONS: These results prove
      that a large number of hospital employees are smokers. However, many are willing
      to give up the habit. We should therefore encourage these people to give up
      smoking and help them by different means such as: anti-smoking advice, medical
      advice and health education. We propose to declare hospitals as "Non-Smoking
      Area" as of the year 2000 which includes employees, patients and visitors,
      according to the WHO "Health for All." program.

PMID- 9546866
TI  - [Epidemiology of leprosy through the study of frequency of visits to the Trillo
      Specialized Hospital in 1943-1995].
AB  - BACKGROUND: The purpose of this study is to describe the social-demographic and
      clinical profile of hospitalised leprosy patients and to check whether typology
      has changed during the history of the centre. METHODS: Descriptive and
      retrospective study, performed by means of reviewing a sample of the patient
      records registered at the Centre since it was founded in 1943 until 1995. 366
      cases were chosen by means of a systematic random sample and questionnaires
      completed on social-demographic and clinical variables. RESULTS: Most of the
      patients were male (71.9%, IC: 67.3-76.4), young (39.6 years of age, IC: 37.9
      41.4), single (46.2%, IC: 41-51.3%) with low levels of education (illiteracy:
      54.1%, IC: 40-69) with occupations relating to farming (35.5%, IC: 30.6-40.4)
      from Southern Spanish regions (patients from Andalucia 52.8%, IC: 45.8-54). The
      disease showed a family background in 31.1% of cases (IC: 26.4-35.9) and serious
      multibacillary forms (Lepromatose Leprosy 66.1%, IC: 61.2-71), which affected
      lower limbs in 72.1% of cases, heads in 63.1% and upper limbs in 64.4%. Global
      mortality of people admitted to hospital was 31.1% (IC: 26.4-35.9). During the
      surveyed period, patient age increased, and symptoms and mortality decreased. In
      general, hospital stays were for long periods (7.1 years, IC: 6.1-8.1), although
      at the end of the surveyed period, stays decreased considerably, in accordance
      with the duration of treatment (2.2 years). CONCLUSIONS: A Young male, in a
      precarious financial situation living in the South of Spain appear to be the
      patient profile which, with severe initial anatomical symptoms and later
      favourable results may represent the disease in a country with an autocuthonous
      endemy and characteristic epidemiology, which is in the pre-eradication phase.

PMID- 9546867
TI  - [Continuity and longitudinal aspects of care in general practice in four European
      countries].
AB  - BACKGROUND: The objective of the study was to compare continuity and
      longitudinality of care in general practice in four European countries with a
      public salary model. METHODS: Descriptive and prospective study. 63 general
      practitioners/family physicians working in public health centers registered all
      encounters (direct and indirect) over a period of one week in Spain, Finland,
      Portugal and Sweden. RESULTS: 92% of the contacts were office encounters: 75%
      were direct (face to face), the average number of encounters per doctor, per week
      was 103. The principal problem was chronic in 42% of cases and acute in 31%. The
      physician has previous knowledge of the principal problem in 63% of the
      encounters and previous knowledge of concurrent problems in 79%. In 66% of cases
      the doctor has previous knowledge of the patient relatives. CONCLUSIONS: The
      level of continuity and longitudinality is variable; from high to low: Portugal,
      Spain, Sweden and Finland. In Spain the duration of the encounter is short and
      repeated prescription are infrequent. In Portugal there are waitings lists which
      implies low accessibility for acute problems. In Finland general practitioners
      have no patients lists and the care is des-personalized. In Sweden there are
      waiting lists and high use of telephone encounters.

PMID- 9546868
TI  - [Eating and life style habits in primary school student population from Mataro
      (Barcelona) associated with consumption of sugar and TV watching].
AB  - BACKGROUND: Most important trends of knowledge and behaviour are built on
      childhood and adolescence. Thus, to act on non healthy habits at early ages
      should have more impact in the development of later diseases. METHODS: 2,898
      primary school students answered a written self administered questionnaire
      containing items about Dietary habits life-style habits, and familiar
      socioeconomic level. Cluster analysis was used to obtain the profile of student
      groups with higher probabilities to develop the risk habits studied. RESULTS:
      High consumption of television is associated with older ages, refreshments
      intake, and moderate consumption of sugar. On the other hand, high consumption of
      sugar is associated with older ages, usual intake of candies, type of school, low
      intake of raw vegetables, and low consumption of fruits. CONCLUSIONS: Other non
      healthy dietary and lifestyle habits show clustering in high consumers of
      television and/or sugar. The influence of socioeconomic level on getting risk
      habits is well stated; however, the role played by this variable in the results
      of our study remains uncertain, probably due to the utilization of indirect data.
      The resultants profiles suggest that the presence of some non healthy lifestyle
      habits, such as high television and sugar consumption, tends to cluster other
      risk habits in the same person.

PMID- 9546869
TI  - Presence of peptide synthetase gene transcripts and accumulation of ergopeptines
      in Claviceps purpurea and Neotyphodium coenophialum.
AB  - The production of toxic ergopeptine alkaloids by the fungi Claviceps purpurea and
      Neotyphodium coenophialum involves the activity of one or more nonribosomal
      peptide synthetases. Claviceps purpurea and N. coenophialum each have several
      different peptide synthetase genes, fragments of which have been cloned
      previously. An additional Claviceps purpurea peptide synthetase gene was cloned
      by hydridization with one of the N. coenophialum peptide synthetase gene
      fragments. We detected the presence of mRNA from the peptide synthetase genes in
      cultures of different ages grown under conditions favorable or unfavorable for
      ergopeptine production. All four peptide synthetase genes from Claviceps purpurea
      were transcribed under at least some of the experimental conditions. Transcripts
      from three of the four genes were detected under conditions consistent with their
      potential involvement in ergopeptine biosynthesis. All three peptide synthetase
      genes previously identified in N. coenophialum were transcribed during symbiotic
      growth of this fungus with tall fescue, as well as ergopeptine-producing
      cultures. The data show that all of the peptide synthetase genes are transcribed,
      that one of the peptide synthetase genes is dissociated from ergopeptine
      biosynthesis, and, as a result, prioritize the remaining genes for functional
      analyses by transformation-mediated gene disruption.

PMID- 9546870
TI  - Headache and menstrually related disorders: in search of a consensus. Naples,
      Italy, 14 November 1995.

PMID- 9546871
TI  - Review of chronic pelvic pain.

PMID- 9546873
TI  - Iraqi time to PAUSE?

PMID- 9546872
TI  - The use of uterine thermal balloon for treatment of menorrhagia.

PMID- 9546874
TI  - A classic medical mystery.

PMID- 9546875
TI  - Women and herbal medicine in Africa.

PMID- 9546876
TI  - The method and role of mediastinoscopy.

PMID- 9546877
TI  - Infection control: HIV/AIDS and other bloodborne pathogens.

PMID- 9546878
TI  - Nursing informatics--what on earth?

PMID- 9546879
TI  - Unannounced JCAHO survey.

PMID- 9546880
TI  - MI mortality outpacing growth of chest pain centers.

PMID- 9546881
TI  - Divers' treasure--hyperbaric oxygen therapy.

PMID- 9546882
TI  - Nursing under pressure.

PMID- 9546883
TI  - Mutual recognition practice model a step closer to reality.

PMID- 9546884
TI  - Volunteers are angels.

PMID- 9546886
TI  - A run in the sun.

PMID- 9546885
TI  - Relief for migraine sufferers.

PMID- 9546887
TI  - Humility--a misplaced virtue.

PMID- 9546888
TI  - Mentoring APRN students.

PMID- 9546889
TI  - Programs that will certainly benefit the patients in our service area.

PMID- 9546890
TI  - An Octopus in the OR.

PMID- 9546891
TI  - High-tech nursing in interventional radiology.

PMID- 9546892
TI  - A critical care nurse tries home care.

PMID- 9546894
TI  - Humility--a misplaced virtue.

PMID- 9546893
TI  - Respiratory syncytial virus: a new approach to an old disease.

PMID- 9546895
TI  - Coming to America.

PMID- 9546896
TI  - Breaking barriers: a Robinson family tradition. Interview by Catherine Campion.

PMID- 9546897
TI  - I.v nurses celebrate.

PMID- 9546898
TI  - Recipe for health: laughter and killer cells.

PMID- 9546899
TI  - Behavioral modification program equals healthy lifestyle.

PMID- 9546900
TI  - APRNs tap vast Internet resources.

PMID- 9546901
TI  - ANAC conference highlights innovations in HIV/AIDS care.

PMID- 9546902
TI  - Infection control: HIV/AIDS and other bloodborne pathogens.

PMID- 9546903
TI  - Home care conference update.

PMID- 9546904
TI  - A look at umbilical cord blood.

PMID- 9546905
TI  - Medical news rings in 1998.

PMID- 9546906
TI  - Rehab nursing: more than you may think.

PMID- 9546907
TI  - MI mortality outpacing growth of chest pain centers.

PMID- 9546908
TI  - Assisted suicide: an "answer" fraught with questions.

PMID- 9546909
TI  - Acute myocardial infarction in a young woman with systemic lupus erythematosus.
AB  - A young woman was diagnosed with systemic lupus erythematosus at the age of 7
      years and incurred an acute myocardial infarction at the age of 17 years. Her
      risk factors for coronary artery disease include hypertension,
      hypercholesterolemia, a relatively long disease duration, a fairly active disease
      as evidenced by the history of nephrotic syndrome and other organ system
      involvement, and a long history of prednisone use. It is difficult to determine
      the etiology of this patient's acute myocardial infarction without coronary
      artery histopathology, but aspects of her presentation (a history of virulent
      systemic lupus erythematosus, and the angiographic findings of ectasia and
      aneurysm) suggest that coronary arteritis was the etiology of her accelerated
      coronary artery disease and subsequent myocardial infarction. Acute myocardial
      infarction is an uncommon occurrence in premenopausal women less than 30 years
      old.35 These patients are typically found to have an associated systemic disease
      such as diabetes mellitus or familial hypercholesterolemia. Systemic lupus
      erythematosus is a less common systemic disease associated with premature
      coronary artery disease. Mechanisms of acute coronary syndromes in these patients
      include accelerated atherosclerosis, active coronary vasculitis, and/or vasospasm
      with superimposed thrombosis.

PMID- 9546911
TI  - Quality of life in patients with intermittent claudication: relationship with
      laboratory exercise performance.
AB  - In patients with peripheral arterial disease, limitation of exercise capacity
      will reduce the level of everyday physical activity and affect the quality of
      life. This study was designed (1) to examine the health-related quality of life
      of patients with intermittent claudication, and (2) to verify whether treadmill
      performance is related to the patient's perceived ability to function in the
      community. In 251 patients with intermittent claudication and 89 matched normal
      subjects, quality of life was assessed by a general health index questionnaire,
      the McMaster Health Index Questionnaire (MHIQ), which covers three dimensions of
      life (physical, social and emotional function). The maximal walking capacity of
      intermittent claudication patients was measured by the treadmill test. When
      controls were compared to intermittent claudication patients using the MHIQ, it
      was found that intermittent claudication patients showed a significant (p < 0.01)
      impairment of 'general health' and lower scores for physical (0.90 +/- 0.17 vs
      0.65 +/- 0.17; p < 0.01), social (0.71 +/- 0.11 vs 0.63 +/- 0.12; p < 0.01) and
      emotional (0.75 +/- 0.17 vs 0.65 +/- 0.15; p < 0.01) function. Age, gender and
      work status had a significant impact upon health scores in several areas.
      Treadmill performance did not correlate with social or emotional function,
      whereas there was a small but significant relationship between maximal walking
      capacity and physical function scores (r = 0.197; p < 0.01). This study suggests
      that impairment in quality of life experience by patients with intermittent
      claudication poorly correlates with the reduced exercised capacity assessed by
      the treadmill test. Therefore, the evaluation of medical and surgical treatment
      of intermittent claudication should include the administration of a questionnaire
      for quality of life assessment.

PMID- 9546910
TI  - The vascular biology of S-nitrosothiols, nitrosated derivatives of thiols.
AB  - Nitric oxide (NO) is a simple heterodiatomic molecule with a broad range of
      biologic actions. In the cardiovascular system NO serves as an endothelium
      dependent vasodilator, an antithrombotic agent, an antiproliferative molecule,
      and a regulator of cardiac contractility. Owing to its reactivity under
      physiologic conditions, accumulating data suggest that NO forms derivatives with
      several classes of biologic compounds. One group of biochemical functionalities
      that serves this role is that of thiols, which can form thionitrites or S
      nitrosothiols with NO. In this paper we will examine the effects of the
      biologically known and the chemically produced S-nitrosothiols on the
      cardiovascular system in order to understand better what role these compounds may
      play in physiologic and pathologic states.

PMID- 9546912
TI  - Images in vascular medicine. Adventitial cystic disease of the popliteal artery.

PMID- 9546913
TI  - Claudication as an 'orphan disease': rationale and goals of drug therapy for
      peripheral arterial disease.
AB  - Patients with peripheral arterial disease are often perceived to suffer from a
      disorder whose pathogenesis and symptoms are not amenable to drug therapies. This
      clinical misperception remains prevalent despite an abundance of data suggesting
      that diverse pharmacotherapies may modulate the natural history of this disease.
      Patients with chronic limb arterial occlusive disease suffer from a disease that
      is characterized by: (1) a prolonged asymptomatic state that can be identified by
      simple physical examination and confirmed by measurement of the ankle brachial
      index; (2) a multi-year period of symptomatic claudication; and (3) a variable
      rate of progression to critical limb ischemia or acute arterial occlusion. This
      stage-dependent disease progression is mediated via the dynamic, but as yet
      incompletely understood, interaction of factors that elicit endothelial
      dysfunction, atherogenesis, and thrombosis. Current data suggest that each of
      these contributory disease processes can be modulated by extant
      pharmacotherapies. Additionally, many novel pharmacotherapeutic agents that are
      currently under investigation may further improve the ability of clinicians to
      modulate these fundamental biologic processes. Pharmacologic therapies should be
      targeted to decrease the rate of limb arterial disease progression, to improve
      limiting symptoms, and to prolong life. Symptoms of claudication can be
      objectively assessed via both exercise testing and disease-specific
      questionnaires. The presence of lower extremity atherosclerotic disease is
      predictive of the presence of coronary heart disease and a foreshortened five
      year survival. Current data suggest that clinical investigations should be able
      to effectively stratify this relative risk via use of both clinical variables
      (e.g., age, diabetes mellitus, tobacco use, etc.) or by measurement of the ankle
      brachial index (ABI). The role of the physician is to decrease suffering and to
      prolong life. Judicious administration of medical therapies can play a critical
      role in helping the vascular practitioner accomplish these goals.

PMID- 9546914
TI  - Experimental models of chronic lower extremity arterial occlusive disease:
      lessons for drug development.
AB  - Peripheral vascular disease is the result of chronic vascular insufficiency. As
      the vascular insufficiency of the lower limbs progressively deteriorates, the
      condition progresses from intermittent claudication (pain upon exercise) to pain
      at rest and gangrene. In very severe cases amputation of the leg may be
      necessary. Whilst dieting, cessation of smoking and physical exercise all
      beneficially affect the progression of the disorder, the available drug therapy
      is of limited benefit. Very effective pharmacological agents capable of
      alleviating the symptoms of chronic peripheral vascular disease have not been
      developed. In order to mimic the vascular insufficiency of intermittent
      claudication, an animal model was developed in rats. This involves short-term and
      long-term 6-10 weeks ligation of the femoral artery of the rat. As demonstrated
      using measurements of hindlimb skeletal muscle, blood flow, pO2, metabolism and
      function, a model of intermittent claudication was produced. Using this model,
      the beneficial effects of physical training was demonstrated. Physical training
      induced an increase in blood flow and a greater capacity for aerobic metabolism
      in the partially ischaemic skeletal muscle. The effect of vasodilators has also
      been examined in this model; in contrast to agents such as Ca2+ antagonists, K+
      channel openers appear to improve nutritional blood flow and metabolism in the
      afflicted skeletal muscle. This model can also be utilized to demonstrate the
      effects of haemorrheological interventions and of agents modulating muscle
      metabolism. However, additional effort is required to develop models for the
      evaluation of efficacy of antiatherothrombotic drugs.

PMID- 9546915
TI  - Microvascular changes in arterial occlusive disease: target for pharmacotherapy.
AB  - The main techniques which have been used to study skin microcirculation in
      patients with peripheral arterial occlusive disease include intravital microscopy
      with and without the use of fluorescent dyes, laser Doppler fluxmetry and
      transcutaneous oximetry. In patients with severe ischaemia (rest pain or
      incipient gangrene) the number of perfused skin capillaries is reduced. Parallel
      to the decreased number of microvessels containing blood, transcutaneous oxygen
      tension is low or even approaches the zero level. The tendency to oedema
      formation is documented by increased leakage of intravenously injected sodium
      fluorescein at the capillary apex of foot skin ('candlelight phenomenon'). Laser
      Doppler flux at rest may still be within the normal range even in advanced
      disease, since the sample volume of these instruments also contains non-nutritive
      shunt vessels. However, reactive hyperaemia after arterial occlusion is decreased
      and delayed in peripheral ischaemia. Whereas rhythmic low-frequency vasomotion is
      significantly enhanced in patients with intermittent claudication, vasoparalysis
      with no flux fluctuations prevails in patients with critical ischaemia.

PMID- 9546916
TI  - Skeletal muscle metabolism as a target for drug therapy in peripheral arterial
      disease.
AB  - Peripheral arterial disease (PAD) is an atherosclerotic disease which modifies
      lower extremity hemodynamics. There is considerable evidence that skeletal muscle
      metabolism is altered in PAD. Several studies have demonstrated altered
      mitochondrial enzyme content in PAD muscle as compared with controls, and enzyme
      activity may not increase normally in PAD with exercise training. A variety of
      metabolic intermediates, including acylcarnitines, accumulate in muscle of PAD
      patients, suggesting incomplete oxidative metabolism. Studies employing 31P-NMR
      (nuclear magnetic resonance) also suggest a metabolic myopathy in PAD.
      Strikingly, while hemodynamics do not predict claudication-limited performance,
      metabolic injury as evidenced by acylcarnitine accumulation is strongly
      correlated with patients' functional status in PAD. Further, exercise
      rehabilitation improves claudication-limited performance without modifying large
      vessel hemodynamics. The stress placed on skeletal muscle during exercise in PAD
      and the observed evidence of metabolic dysfunction is similar to
      ischemia/reperfusion injury in cardiac muscle. Recognition of the role of
      cellular metabolic injury and function in PAD has formed the basis for novel
      therapeutic strategies in this disease.

PMID- 9546917
TI  - The demographics of claudication and the aging of the American population.
AB  - Most peripheral artery disease is of ischemic atherosclerotic etiology and
      manifested as intermittent claudication (IC). Death and disability from
      atherosclerotic cardiovascular disease (CVD) is a growing problem because of the
      rapidly increasing elderly segment of the population. By the year 2015 the
      elderly will constitute 14.8% of Americans. Of the total 255 million, 13.8
      million are over age 75 years and 9 million are women. On reaching age 65 years,
      the average remaining lifetime is 17.4 years. In the USA this 11% of the
      population accounts for 29% of the health costs and 70% of all deaths are
      attributable to cardiovascular disease. About 9.6% of cardiovascular events are
      due to peripheral artery disease manifested as IC requiring 777,000 office visits
      and 63,000 hospitalizations. Also, 17,400 deaths each year are attributed
      directly to this cause. The biennial incidence of IC in the Framingham Study was
      7.1 per 1000 for men and 3.6% for women, increasing with age in both sexes up to
      age 75 years. At all ages there is a distinct male predominance. In the 35-64
      year age range IC incidence is virtually identical to that of cardiac failure and
      stroke, but only one-third of CHD incidence. Beyond age 65 years IC incidence is
      only half that of other atherosclerotic cardiovascular conditions. The incidence
      of carotid bruits and non-palpable pedal pulses is virtually identical in the two
      sexes; only femoral bruits are male predominant. At time of diagnosis of IC one
      in three already have overt evidence of CHD, stroke or congestive heart failure
      (CHF). In those free of these at outset CHD and strokes occur at two to three
      times the general population rate and CHF 3.5-4.5 times the rate of persons
      without IC. Within 10 years of IC onset 43% develop CHD, 21% strokes and 24%
      cardiac failure. Carotid and femoral bruits are likewise harbingers of other
      atherosclerotic CVD. As many as 45% of IC victims lose their symptoms for
      extended periods. Survival following onset of IC is only two-thirds of that
      general population; after 10 years 60% died. This high mortality is largely
      attributable to coexistent cardiovascular impairments. A risk profile comprising
      the major cardiovascular risk factors predicts occurrence of IC even better than
      CHD. IC risk increases progressively with burden of the risk factors. With an
      aging population of increased size peripheral artery disease is a problem of
      increasing dimensions. Attention to comorbid conditions is essential if survival
      is to be improved. Because IC shares many of the same risk factors, measures to
      prevent CHD, CHF and strokes should also reduce IC risk.

PMID- 9546918
TI  - The correlation between symptoms and non-invasive test results in patients
      referred for peripheral arterial disease testing.
AB  - The WHO/Rose questionnaire has served as the epidemiologic and clinical standard
      in the assessment of leg pain in patients with peripheral arterial disease (PAD)
      for over three decades. However, the structure of this questionnaire does not
      allow assessment of leg-specific (i.e. right versus left) symptoms. We studied
      508 patients aged 39-95 years (mean 68 years), initially referred for PAD non
      invasive testing. A revised questionnaire, the San Diego Claudication
      Questionnaire, was administered which allowed determination of leg-specific
      symptoms and evaluated thigh and buttock as well as calf pain. Leg-specific
      symptoms were categorized into no pain, pain at rest, non-calf claudication, non
      Rose calf claudication, and Rose claudication. At the same visit, the ankle
      brachial index, the toe brachial index, and peak posterior tibial flow velocity
      were measured by Doppler ultrasound and five categories of non-invasive results
      by type and severity of PAD were defined. Legs with previous intervention (Rx),
      surgery or angioplasty, were evaluated separately. Claudication was reported in
      42% of no Rx legs and 50% of Rx legs; 40% of claudication was atypical (not
      Rose); 64% of no Rx and 81% of Rx legs had PAD by non-invasive testing, and 27%
      of affected legs had severe PAD. The correlation between the severity of symptoms
      and the severity of ipsilateral PAD in no Rx legs was r = -0.40, p < 0.001. In Rx
      legs, this correlation was somewhat less (r = 0.27, p < 0.001) due to more
      symptomatology at lesser degrees of PAD, suggesting reporting bias and/or more
      residual disease than evident from non-invasive testing. To our knowledge, these
      results provide the first comparison between a standardized assessment of leg
      pain and the severity of ipsilateral PAD by non-invasive testing.

PMID- 9546919
TI  - New antithrombotics for the treatment of acute and chronic arterial ischemia.
AB  - The established antithrombotic agents are effective but they have limitations
      which have provided opportunities for the development of new antithrombotic
      compounds. Of these new agents, the antithrombin III-independent thrombin
      inhibitors and the platelet GPIIb/IIIa receptor antagonists are the most advanced
      in their development. Other new antithrombotic agents include the antithrombin
      III-independent factor Xa inhibitors, activated protein C, soluble thrombomodulin
      and tissue factor pathway inhibitor. Of the GPIIb/IIIa antagonists, the humanized
      7E3 antibody and integrin have been evaluated in phase III studies. The 7E3
      antibody was effective in preventing both short-term and longer-term
      complications of coronary angioplasty. The antithrombin III-independent thrombin
      inhibitors hirudin and hirulog have also been evaluated in phase III studies. The
      studies with hirudin as an adjuvant to coronary thrombolysis had to be terminated
      and restarted at lower dosages because of an unacceptable incidence at
      intracranial hemorrhage and the study with hirulog produced equivocal results.

PMID- 9546920
TI  - Therapeutic angiogenesis: a new frontier for vascular therapy.
AB  - Angiogenic cytokines constitute a potentially novel form of therapy for patients
      with cardiovascular disease. The feasibility of using recombinant formulations of
      angiogenic growth factors to expedite and/or augment collateral artery
      development in animal models of myocardial and hindlimb ischemia--'therapeutic
      angiogenesis'--has now been well established. These studies have suggested that
      two angiogenic growth factors in particular--basic fibroblast growth factor and
      vascular endothelial growth factor--are sufficiently potent to merit further
      investigation. More recently, experiments performed in our laboratory have
      indicated that, in the case of vascular endothelial growth factor--a secreted
      protein--similar results may be achieved by percutaneous arterial gene transfer.
      Further laboratory and clinical studies may yield promising insights into the
      fundamental basis for native as well as therapeutic angiogenesis, and at the same
      time more explicitly define the manner in which therapeutic angiogenesis may be
      successfully incorporated into clinical practice.

PMID- 9546921
TI  - The influence of apolipoprotein E on the interactions between normal human very
      low density lipoproteins and U937 human macrophages: heterogeneity among persons.
AB  - Apolipoprotein E (apo E) can mediate the cell binding of normal human very low
      density lipoproteins (VLDL). However, the extent to which apo E is involved in
      the cell binding and uptake of VLDL from different normolipidemic persons is not
      well defined. The VLDL (d < 1.006 g/l) of eight subjects were fractionated into
      VLDL with apo E and without apo E using a monoclonal antibody that binds to the
      LDL receptor recognition region of apo E. VLDL particles that expressed the 1D7
      binding region of apo E comprised an average of 34% (range 7-51%) of the VLDL
      particles. Anti-apo E blocked an average of 43% (range 8-63%) of the binding of
      unfractionated VLDL to U937 cells. Anti-apo E blocked a similar proportion of
      binding to U937 cells of three VLDL subfractions of different density ranges
      (Sf20-60, Sf60-100, Sf100-400). The proportion of the VLDL particles that
      contained apo E correlated with the extent of uptake of the total VLDL by U937
      cells, but not with stimulation by total VLDL of cholesterol ester formation. The
      binding to cells of VLDL without apo E varied by six-fold among persons, and
      caused most of the binding of the total VLDL of some subjects. Therefore,
      normolipidemic VLDL contains particles across its density range that use apo E to
      bind to U937 macrophages. In some VLDL samples, apo E provides most of the cell
      binding activity, whereas in others the binding activity occurs by other means.

PMID- 9546922
TI  - Hypothermia and rewarming after hypothermic exposure alter venous relaxation.
AB  - Hypothermia has pathophysiological consequences on endothelial and smooth muscle
      cell function. This study investigates the impact on venous relaxation of
      hypothermia and rewarming following hypothermic exposure. In vitro isometric
      relaxation responses of norepinephrine precontracted rabbit external jugular
      veins to a panel of endothelium-dependent and -independent agonists were assessed
      in controls at 37 degrees C, and in an experimental group after cooling to 20
      degrees C and after rewarming to 37 degrees C. On cooling, the endothelium
      dependent responses to acetylcholine became multiphasic with initial contraction
      at low concentrations followed by relaxation at higher concentrations, the
      maximum of which was significantly diminished compared to controls. Incubation
      with indomethacin did not affect this response. Rewarming re-established a
      monophasic dose-dependent acetylcholine induced relaxation response but the
      maximal response was significantly augmented. This augmentation in relaxation on
      rewarming could be prevented by preincubation with indomethacin. The maximal
      response to calcium ionophore was reduced at 20 degrees C and augmented upon
      rewarming to 37 degrees C. All veins relaxed in a dose-dependent manner to the
      non-endothelium-dependent agonists forskolin and sodium nitroprusside; the
      maximal responses were significantly reduced at 20 degrees C and returned to
      normal upon rewarming. This study suggests that short-term exposure of venous
      tissue to hypothermia impairs the vessel's ability to produce endothelium
      dependent relaxation. Rewarming does not re-establish normal endothelium
      dependent relaxation but results in an enhanced, partially indomethacin
      sensitive, response which appears to be independent of changes in non-endothelium
      dependent mediated relaxation.

PMID- 9546923
TI  - The impact of angiotensin converting enzyme inhibitors on the arterial wall.
AB  - There is recent interest in the possibility that angiotensin converting enzyme
      inhibitors (ACE inhibitors) may reduce the damage inflicted on the arterial wall
      by common cardiovascular risk factors such as hypertension, hyperlipidaemia and
      ageing. The efficacy of these drugs in blood pressure reduction is accepted, but
      whether there is an excess benefit on arterial structure and function, conferred
      by use of ACE inhibitors over more traditional antihypertensives, is still under
      debate. There is also evidence in animal models to suggest that ACE inhibition is
      effective in reduction of arterial damage due to experimental hyperlipidaemia.
      ACE inhibitors not only reduce the conversion of angiotensin I and angiotensin
      II, which can interact with the sympathetic nervous system, but also prevent the
      degradation of bradykinin. This means that ACE inhibitors have several potential
      mechanisms through which they could suppress intimal hypertrophy and prevent
      endothelial dysfunction, which is believed to precede arteriosclerosis in man.
      Although much further work is needed to clarify the mechanism underlying the
      beneficial effects on the arterial wall of this group of drugs, they do appear to
      have significant potential in the effort to reduce cardiovascular mortality and
      morbidity, especially in high risk groups.

PMID- 9546924
TI  - Can lower limb ultrasonography replace arteriography?
AB  - Although duplex ultrasonography offers a number of theoretical and practical
      advantages over arteriography for the assessment of lower limb arterial disease,
      it has not yet been widely accepted into clinical practice. This article reviews
      the current status of lower limb arterial duplex and concludes that arteriography
      should no longer be regarded as the diagnostic 'gold-standard' and that duplex
      ultrasonography should now be the first line investigation in patients with lower
      limb arterial disease.

PMID- 9546925
TI  - Carotid angioplasty.
AB  - Aspirin and carotid endarterectomy represent the current method of prophylaxis
      against stroke in patients with symptomatic high grade carotid stenoses. Whilst
      balloon dilatation and stent placement is an accepted form of recannalization,
      elsewhere in the arterial circulation the technique is in its infancy within the
      supra-aortic vessels. Carotid endarterectomy is expensive, requires a general
      anaesthetic and is associated with an acceptable complication rate as
      demonstrated by the ECST and NASCET studies. The author's experience in 55
      patients with symptomatic high grade atherosclerotic disease is described with a
      disabling stroke rate at 30 days similar to the surgical series (5%). Long-term
      follow-up is awaited. Metallic intra-arterial stents provide the opportunity to
      reduce the immediate postintervention residual stenosis and possibly reduce the
      long-term restenosis rate. Modifications of the technique are in development and
      may reduce the cerebral embolization that occurs during the procedure.

PMID- 9546926
TI  - Quality control during carotid endarterectomy.
AB  - Although some form of quality control assessment is standard practice following
      virtually all forms of peripheral vascular reconstruction, it is seldom applied
      to carotid endarterectomy. This is despite the fact that the complications
      following endarterectomy can be catastrophic, are often related to technical
      error and are not easily remedied. A number of novel quality control techniques
      are now available. This review article summarizes the application of these
      methods to ensuring optimal surgical practice in patients undergoing carotid
      endarterectomy.

PMID- 9546927
TI  - Images in vascular medicine. Buerger's disease (thromboangiitis obliterans).

PMID- 9546928
TI  - The PACK trial: morbidity and mortality effects of ketanserin. Prevention of
      Atherosclerotic Complications.
AB  - A total of 3899 patients over 40 years old who had documented intermittent
      claudication for at least 2 months and in whom the ratio of systolic blood
      pressure in the ankle to that in the arm was < 0.85 in both arteries of at least
      one foot were recruited in a double-blind, randomized, placebo-controlled trial
      after a single-blind run-in period of placebo treatment for 1 month. Trial drug
      was ketanserin 40 mg three times daily. The first primary event after
      randomization was the endpoint. Primary events were definite myocardial
      infarction, major stroke, amputation above the ankle, excision of ischaemic
      viscera, and death due to other vascular causes. There were 136 study endpoints
      in the 1930 patients treated with ketanserin, who were followed up for 2063
      patient-years, and 132 study endpoints in the 1969 patients treated with placebo,
      who were followed up for 2129 patient-years. A harmful interaction of ketanserin
      and potassium-losing diuretics resulted in an increase in the number of deaths.
      After patients taking potassium-losing diuretics or antiarrhythmic agents were
      excluded, a secondary analysis showed that there were 65 endpoints in 1514
      patients taking ketanserin and 87 in 1577 patients taking placebo, a reduction of
      23% in the number of study endpoints in those taking ketanserin. The treadmill
      walking distance and ankle systolic pressure were measured in a predetermined
      subset of 594 patients. Complete datasets at the beginning and end of 1 year's
      treatment with ketanserin or placebo were available in 436 patients. There was no
      difference between the groups in the improvement in pain-free treadmill walking
      distance. The placebo effect on treadmill walking distance increased continuously
      for at least 1 year at the rate of about 15% every 6 months. There was no
      significant change in either group in the ankle systolic pressure at the end of
      the treatment period, but, in the group given ketanserin, brachial systolic
      pressure was decreased and the ankle/arm systolic pressure ratio therefore
      increased.

PMID- 9546929
TI  - The STIMS trial: the ticlopidine experience and its clinical applications.
      Swedish Ticlopidine Multicenter Study.
AB  - The mortality in patients with intermittent claudication can be reduced by
      treatment with ticlopidine. This is the clinically most significant result from
      STIMS, the Swedish Ticlopidine Multicenter Study. During an average treatment
      period of 5.6 years, 153 of the 687 patients died, 26.1% in the placebo group and
      18.5% in the ticlopidine group (RR0.7, p = 0.015). The incidence of fatal
      vascular events in the two groups was 12% and 6%. In terms of lives saved per
      years of treatment, STIMS showed that by treating 200 claudicants for 5 years one
      can save 13 from a cardiovascular death, not merely dying from something else as
      treatment was associated with a reduced total mortality as well. The
      interpretation of the on-treatment analysis is that for those who tolerate the
      drug the combined vascular morbidity and mortality rate is lowered from 24% to
      14%. The disadvantage is that many patients do not tolerate ticlopidine. In
      STIMS, 22% (2.5 times as many as in the control group) had to stop medication
      because of gastrointestinal side-effects. Although ticlopidine is associated with
      an increased risk of leukopenia, the risk in absolute numbers is small: according
      to STIMS, 4% during 5.6 years. All events were reversible. The 1.4% incidence of
      thrombocytopenia did not seem to be associated with ticlopidine treatment.

PMID- 9546930
TI  - The pentoxifylline experience: exercise testing reconsidered.
AB  - This paper critically reviews the methodology used in clinical trials in chronic
      occlusive arterial disease (COAD) stage II (intermittent claudication) patients.
      The reasons for choosing internationally accepted standard treadmill settings as
      well as its limitations are discussed. Emphasis is put on the discussion of valid
      trial endpoints such as hemodynamic surrogates and clinically oriented
      parameters. Reasons for a spontaneous and treatment-unrelated improvement in
      claudication distance are elucidated, and variables which may be used for the
      definition of patient subsamples showing a high frequency of a pronounced
      treatment response (treatment responder populations) are presented. The magnitude
      of claudication distance improvement that might be considered clinically relevant
      is discussed in the light of the European Union guidelines for clinical trials in
      COAD patients. Results achieved with pentoxifylline are presented in context with
      all variables mentioned above.

PMID- 9546931
TI  - Prostanoid drug therapy for peripheral arterial occlusive disease--the European
      experience.
AB  - The most serious threat to a claudicant is not the possible future need for a
      major amputation, but rather that the medium-term mortality is two to three times
      that of the general age-matched population. In patients with more severe disease
      in the legs, approximately 45% will have had a major amputation or be dead within
      a year of developing rest pain, ulcers or gangrene. These are the challenges for
      pharmacotherapy in peripheral arterial occlusive disease. In the short and medium
      term, pharmacotherapy can only have a significant effect by modifying the
      microcirculatory response to the low perfusion pressure caused by the arterial
      disease. The microcirculatory changes in the leg in severe leg ischaemia are ill
      understood, but theoretically a number of pharmacological effects could be
      beneficial. In practice, the only type of drugs widely tested clinically in
      severe leg ischaemia are prostacyclin and its analogues. In the last 12 years the
      results of properly controlled randomized trials involving patients with chronic
      limb ischaemia have been carried out in approximately 2000 patients in Europe.
      The largest number were entered into trials using the prostacyclin analogue
      iloprost. Some of these trials have shown a significant benefit compared to
      placebo in terms of major amputation or death during the 6 months following a 2-4
      week course of intravenous iloprost. The possible future indications for this
      type of therapy, as well as the use for prostaglandins in claudicants, is
      discussed.

PMID- 9546932
TI  - Thrombolysis or operation for peripheral arterial occlusion.
AB  - Patients with peripheral arterial occlusion may be treated with one of three
      distinct treatment strategies: observation and/or anticoagulation alone,
      operative intervention, or catheter-directed thrombolytic therapy. The severity
      of symptoms is the most important clinical parameter with which to formulate
      clinical strategies. Patients with non-lifestyle limiting claudication may be
      best managed without arteriographic investigation, managing symptoms
      conservatively with exercise, cessation of smoking, and occasionally the oral
      pharmacologic agent pentoxifylline. Patients with threatened limbs in the form of
      rest pain or tissue loss carry a high risk of limb loss without intervention.
      These patients should undergo arteriography with consideration of endovascular
      intervention for focal lesions and bypass grafting for more diffuse disease.
      Patients with more acute symptoms may be best treated with catheter-directed
      thrombolytic therapy, addressing unmasked lesions responsible for the occlusion
      with an operative or endovascular approach. In all cases, the appropriate therapy
      must be tailored to the clinical presentation, the anatomic distribution of
      disease, and the experience of the clinical team.

PMID- 9546933
TI  - Practical equations to predict claudication pain distances from a graded
      treadmill test.
AB  - Treadmill testing is used to estimate the severity of claudication, but routine
      use is not practical or cost-effective in all settings. Thus, the purposes of
      this study were: (1) to develop and cross-validate prediction equations for
      treadmill claudication pain distances in a heterogeneous cohort of peripheral
      arterial occlusive disease patients, and (2) to determine if the regression
      equations were more accurate in assessing claudication distances than self
      reported distances of patients. Medical history, vital signs, resting
      ankle/brachial systolic pressure index (ABI), and claudication distances during a
      graded treadmill test were obtained on a validation group of 178 claudicants and
      on a cross-validation group of 94 claudicants. The independent predictors of
      claudication pain distances of the validation group were ABI, body mass index,
      gender, and current smoking status, with multiple correlation coefficients of R =
      0.73 and R = 0.82 for the distances to onset and to maximal pain, respectively.
      These equations were successfully cross-validated on an independent group of
      claudicants, as the predicted distances to onset of claudication pain (167.2 +/-
      102.6 m) and to maximal pain (354.6 +/- 154.3 m) were similar (p = 0.99) to
      measured distances (169.1 +/- 127.8 m and 356.6 +/- 181.0 m, respectively).
      However, the self-reported distances to onset (89.5 +/- 126.3) and to maximal
      claudication pain (189.2 +/- 284.3) were 1-2 blocks less than either the measured
      or predicted distances (p < 0.01). It is concluded that claudication pain
      distances during an incremental treadmill test can be more accurately estimated
      from a composite of variables obtained during medical screening than by relying
      on the self-report of patients. Consequently, in clinical settings where
      treadmill testing is impractical, the functional severity of claudication can be
      assessed without exercise testing.

PMID- 9546934
TI  - Heparin administration via nomogram versus a standard approach in venous and
      arterial thromboembolic disease.
AB  - To determine whether heparin administered by continuous intravenous infusion
      using a nomogram is superior to a random dosing scheme, we performed a
      prospective, randomized comparative trial in 161 patients. Patients were
      prospectively randomized to one of three groups. Group I received an intravenous
      bolus of 5000 IU of heparin followed by heparin administration according to a
      modification of a previously published nomogram. Group II patients received a
      5000 IU intravenous bolus of heparin followed by continuous intravenous heparin
      infusion with dosage adjustment at the discretion of the treating physician.
      Group III patients received a continuous intravenous heparin infusion with dosage
      adjustments at the discretion of the treating physician without the prior
      administration of a bolus dose. Activated partial thromboplastin time (APTT) was
      obtained at baseline, 6 h after each heparin dose adjustment and every morning.
      The mean percent of each patient's APTTs in the subtherapeutic range (< 50 sec)
      over the course of treatment was 9% for group I and 24% for groups II and III, p
      = 0.0001. The three groups had a similar percentage of each patient's APTTs
      within the therapeutic range (50-80 sec). There was a larger percentage of APTTs
      > 80 sec in group I (46%) compared to group II (31%) or group III (32%), p =
      0.01. There were no clinically recurrent deep venous thrombi or arterial
      thromboemboli in any of the groups. Two patients had documented pulmonary emboli
      during heparin therapy (one in group I; one in group II). There was no difference
      in the complication rates of heparin therapy or the need for blood transfusions
      among the three groups. Patients randomized to the heparin nomogram (group I)
      achieved an APTT > 50 sec more frequently than patients in the other two groups.
      Overall, fewer patients in the nomogram group were subtherapeutic, and, when APTT
      levels fell in the subtherapeutic range, the nomogram restored APTTs to the
      therapeutic range faster than the standard methods. The heparin nomogram was
      clearly more effective as a method of heparin dosing than standard methods of
      anticoagulation dosing.

PMID- 9546935
TI  - Felodipine inhibits intimal lesion formation in the hypercholesterolemic rabbit:
      differential effects on endothelial and monocyte determinants of atherogenesis.
AB  - The purpose of this study was to determine if the calcium entry antagonist
      felodipine inhibited intimal lesion formation in hypercholesterolemic rabbits,
      and to determine if this was due to an effect upon monocyte and/or endothelial
      determinants of this interaction. Twenty-three male New Zealand White rabbits
      received the following treatment regimen for 10 weeks: normal chow (NP, n = 3);
      normal chow with felodipine infusion (NF, n = 6); 0.5% cholesterol chow (CP, n =
      7); or 0.5% cholesterol chow and felodipine infusion (CF, n = 7). After 10 weeks
      blood was collected for biochemical measurements and mononuclear cell binding
      assays, and thoracic aortae were harvested for vascular reactivity studies and
      histomorphometry. In the animals receiving normal chow, felodipine did not
      significantly affect blood pressure, plasma cholesterol levels, binding studies,
      vascular reactivity, or structure; therefore these animals were analyzed as one
      group (N). Plasma cholesterol levels were significantly elevated in groups
      receiving the 0.5% cholesterol diet (N, 29 +/- 3 mg/dl; CP, 1221 +/- 73 mg/dl;
      CF, 979 +/- 108 mg/dl). High-density lipoprotein cholesterol was not different
      between the groups (25 +/- 4 vs 23 +/- 4 vs 27 +/- 4 mg/dl; N vs CF vs CP
      respectively; p = NS). Cholesterol feeding markedly augmented the adhesiveness of
      mononuclear cells, as demonstrated by a 250% increase in cell binding. Felodipine
      did not alter the adhesiveness of mononuclear cells in hypercholesterolemic
      animals. Cholesterol feeding significantly impaired endothelium-dependent
      relaxations. Endothelium-dependent relaxations were restored by felodipine
      treatment as reflected by the maximal responses to acetylcholine (40 +/- 7% vs 58
      +/- 4% vs 67 +/- 5%; CP vs CF vs N respectively). The improvement in endothelium
      dependent relaxation in the felodipine-treated animals was associated with a 2.2
      fold reduction in lesion surface area of the thoracic aorta (8.2 +/- 6.3% vs 18.2
      +/- 9.5%; CF vs CP; p < 0.01). Moreover, the intima/media ratio reflecting lesion
      thickness was substantially reduced by felodipine treatment (0.05 +/- 0.02 vs
      0.20 +/- 0.07; CF vs CP; p = 0.006). Ex vivo studies revealed that felodipine
      inhibited the adhesiveness of vascular endothelium, but not mononuclear cells,
      derived from hypercholesterolemic animals. Low-dose felodipine appears to inhibit
      monocyte-endothelial interaction, as indicated by a reduction in the formation of
      lesions in hypercholesterolemic animals. This effect is not due to an alteration
      in adhesiveness of mononuclear cells. The salutary effect of felodipine is
      associated with an increase in vascular nitric oxide activity which may reduce
      endothelial adhesiveness.

PMID- 9546936
TI  - The effect of cigarette smoking on exercise capacity in patients with
      intermittent claudication.
AB  - The purposes of this study were: (1) to determine whether peripheral arterial
      occlusive disease (PAOD) patients who smoked had more severe claudication pain,
      reduced peripheral circulation, and poorer cardiopulmonary measurements at peak
      exercise than non-smoking patients, and (2) to determine whether the differences
      between the smoking and non-smoking patients persisted after controlling for the
      resting ankle/brachial systolic pressure index (ABI). Thirty-eight PAOD patients
      (ABI = 0.59 +/- 0.15, mean +/- SD) who smoked an average of 1.5 packs of
      cigarettes per day over 42 years and 100 PAOD patients (ABI = 0.74 +/- 26) who
      had quit smoking for an average of 7 years were recruited. Smokers refrained from
      smoking on the day of testing. Claudication pain times, oxygen uptake,
      ventilation, leg oximetry, and ankle systolic pressure responses to peak exercise
      were recorded. The smoking group had more severe claudication pain, as maximal
      pain occurred 1:37 min:s sooner during exercise (p < 0.05), and the pain took
      2:21 min:s longer to subside (p < 0.01) compared to the non-smoking group.
      Additionally, at peak exercise the smoking group had a lower oxygen uptake (12.8
      +/- 2.6 vs 13.9 +/- 2.4 ml/kg/min, p < 0.01), a higher ventilation (31.7 +/- 9.2
      vs 27.9 +/- 7.1 liters/min, p < 0.05), and a higher oximeter electrode power (409
      +/- 55 vs 385 +/- 37 mW, p < 0.01) than the non-smoking group. Differences
      between the groups persisted (p < 0.05) after adjusting for resting ABI. It is
      concluded that cigarette smokers with PAOD had more severe claudication pain,
      reduced peripheral circulation, and poorer cardiopulmonary measurements at peak
      exercise than non-smoking patients. These differences were independent of resting
      ABI. Thus, cigarette smoking reduces the exercise capacity of claudicants,
      placing patients who smoke at an even greater risk of living a functionally
      dependent lifestyle.

PMID- 9546937
TI  - Vasodilator responses in the forearm skin of patients with insulin-dependent
      diabetes mellitus.
AB  - The integrity of endothelium-dependent vasodilation in the skin of patients with
      insulin-dependent diabetes mellitus (IDDM) is unclear, especially with respect to
      the role of nitric oxide. To examine this, forearm skin blood flow by laser
      Doppler flowmetry and total blood flow by venous occlusion plethysmography was
      measured in response to brachial artery infusions of an endothelium-dependent
      (methacholine) and -independent (sodium nitroprusside) vasodilator. Peak
      hyperemic forearm blood flow, following 5 min of arterial occlusion, was also
      determined. Responses were compared in 11 control subjects and 16 patients with
      insulin-dependent diabetes mellitus. In ten normal subjects, co-infusion of NG
      monomethyl-L-arginine with methacholine produced a significant reduction in total
      forearm blood flow response to methacholine (p < 0.002), measured by venous
      occlusion plethysmography, as well as vascular conductance (p < 0.001),
      confirming that nitric oxide contributes to this response. In contrast, NG
      monomethyl-L-arginine had no significant effect on the methacholine-induced
      increase in forearm skin blood flow measured by laser Doppler flowmetry
      indicating that factors other than nitric oxide may be involved. Increases in
      forearm skin blood flow in response to methacholine, sodium nitroprusside and to
      an ischemic stimulus were not significantly different between the normal subjects
      and patients with IDDM. Dose-related increases in total forearm blood flow and
      vascular conductance were not significantly different between control subjects
      and diabetic patients during infusions of methacholine. The increases in these
      parameters during infusions of sodium nitroprusside, however, were significantly
      less in the diabetic group than in the control group (p < 0.05) as was the peak
      reactive hyperemic blood flow (p < 0.05). Since skin blood flow was not affected,
      the reduced vasodilator responses to sodium nitroprusside and an ischemic
      stimulus in the diabetic group are in forearm skeletal muscle. The reduced muscle
      blood flow does not reflect a decreased vasodilatory capacity, but rather a
      functional impairment in response to nitric oxide and ischemia since the
      methacholine dilation was normal. The normal vasodilator responses in the forearm
      skin, which is predominantly capillary as opposed to arteriovenous anastomatic
      blood flow, indicate that the response to nitric oxide and an ischemic stimulus
      in this vascular bed is intact in patients with IDDM. This is, therefore, an
      unlikely cause of diabetic skin, complications in these areas.

PMID- 9546938
TI  - Oxidative stress and lipids in diabetes: a role in endothelium vasodilator
      dysfunction?
AB  - Endothelial dysfunction is a key feature of diabetes mellitus and is thought to
      be the major cause of vascular complications associated with the disease. The
      vascular endothelium demonstrates impaired synthesis of vasodilators and
      increased release of procoagulants and vasoconstrictors, defects which
      theoretically could explain the increased incidence of atherosclerosis and
      hypertension found within this patient group. The pathways mediating endothelial
      cell layer dysfunction are unknown, although many candidates have been proposed.
      This review concentrates on the hypothesis that increased oxidative stress
      combined with abnormal plasma lipid composition leads to reduced synthesis of
      endothelial vasodilators and hence endothelial dysfunction. Free radical
      generation is undoubtedly raised in diabetes but the evidence for decreased
      antioxidant status is debatable. The role of antioxidant and lipid-lowering
      therapy is considered, but few studies have directly investigated the effect of
      treatment on vascular function. Concern arises from individual studies of vitamin
      E in diabetic animals which have proved deleterious. Current literature implies
      that a combination therapy of vitamin E and vitamin C may be beneficial, but this
      needs to be investigated further in both animal and human diabetes.

PMID- 9546940
TI  - Current puzzles presented by postmastectomy oedema (breast cancer related
      lymphoedema).

PMID- 9546939
TI  - Prophylaxis against deep venous thrombosis and pulmonary embolism in patients
      with stroke.

PMID- 9546941
TI  - Takayasu arteritis: clinical characteristics and the role of genetic factors in
      its pathogenesis.
AB  - Takayasu arteritis is a chronic vasculitis, the aetiology of which is still
      unknown. Several characteristic clinical manifestations have led scientists to
      consider the possibility of the genetic factors in the aetiology, conjecture
      which is supported by HLA analysis. Recent attention has focused on the different
      clinical manifestations among Asian and South American countries and further
      progress is likely to stem from international network studies.

PMID- 9546942
TI  - Images in vascular medicine. Multiple aortic aneurysms.

PMID- 9546943
TI  - Role of digital artery adrenoceptors in Raynaud's disease.
AB  - Raynaud's disease is characterized by excessive cutaneous vasoconstriction in
      response to ambient cold. A functional disturbance in the local regulation of
      digital vasomotion has been proposed. The purpose of this study was to determine
      whether there is an alteration in the postjunctional adrenergic receptors in the
      digital circulation of patients with Raynaud's disease. Furthermore, we sought to
      determine whether this abnormality was responsible for the excessive cold-induced
      vasoconstriction in these patients. Finger blood flow was measured by strain
      gauge venous occlusion plethysmography in 10 patients with Raynaud's disease and
      in 10 normal volunteers in a 22 degrees C room. Measurements of finger blood flow
      and mean systemic arterial pressure were made during intra-arterial infusions of
      the alpha 1-adrenergic antagonist, prazosin, or the alpha 2-adrenergic
      antagonist, yohimbine, at room temperature and during local cooling of the hand.
      Basal finger blood flow in normal subjects was significantly greater than that of
      patients (8.6 +/- 2.7 vs 1.7 +/- 0.5 ml/100 ml per min; normal vs Raynaud's
      subjects; p < 0.05). In normal subjects, either prazosin or yohimbine induced
      dose-dependent increases in finger blood flow. The maximal increase in finger
      blood flow induced by prazosin was significantly greater than that in response to
      yohimbine (29.2 +/- 10.1 vs 2.8 +/- 2.1 ml/100 ml per min; prazosin vs yohimbine;
      p < 0.05). By contrast, in the Raynaud's patients, prazosin or yohimbine induced
      maximal increases in finger blood flow that were not significant (7.1 +/- 1.8 vs
      5.0 +/- 2.2 ml/100 ml per min; prazosin vs yohimbine; p = NS). The response to
      prazosin in Raynaud's patients was significantly less than that of the normal
      volunteers (p < 0.05). In normal subjects, during intra-arterial infusion of
      vehicle alone, cooling induced a 52.6 +/- 5.8% reduction in finger blood flow.
      This cold-induced vasoconstriction was blunted, but not qualitatively altered, by
      either adrenergic antagonist. In the Raynaud's patients, during the intra
      arterial infusion of the vehicle, cooling induced a 68.2 +/- 7.8% reduction in
      finger blood flow. Infusion of either adrenergic antagonist blunted, but did not
      qualitatively alter, the response to cold. Finger blood flow is less in patients
      with Raynaud's disease than in normal subjects when studied in a 22 degrees C
      room. In normal subjects, postjunctional alpha 1-adrenergic receptors appear to
      predominate in the control of digital vasoconstriction. Postjunctional alpha 1-
      and alpha 2-adrenoceptors play an equal role in adrenergic regulation of finger
      blood flow in patients with Raynaud's disease. In both normal and Raynaud's
      subjects, selective antagonism of alpha 1- or alpha 2-adrenergic receptors does
      not abolish local cold-induced vasoconstriction. Therefore, it is likely that a
      nonadrenergic mechanism contributes to local cold-induced vasoconstriction.

PMID- 9546945
TI  - Changes in the amplitude of cyclic load biphasically modulate endothelial cell
      DNA synthesis and division.
AB  - Several physical factors, including shear stress and cyclic load, modulate the
      ability of endothelial cells to respond to injury. The objective of these
      experiments was to test the hypothesis that cyclic mechanical load stimulates
      endothelial cell DNA synthesis and division in vitro. Rabbit aortic endothelial
      cells were cultured on Flex I flexible-bottomed culture plates, and subjected to
      load amplitudes of increasing magnitude (0, 0.18, 0.24 and 0.27 load at 1 Hz)
      using a Flexercell strain unit. Cells were harvested enzymatically and cell
      numbers determined on days 1, 3 and 5 after initiating the load regimen. DNA
      synthesis was quantified after trichloroacetic acid precipitation of
      [3H]thymidine-labeled cells from: (1) whole culture wells and (2) areas of
      minimum and maximum strain in culture cells. Data were analyzed using analysis of
      variance and a Tukey's test (n = 6 observations/strain regimen per day in
      triplicate). Results from analysis of endothelial cells in whole, subconfluent
      cultures showed that cells subjected to strains of 0.18 had a decreased rate of
      cell division (76% of control) and DNA synthesis (63% of control), while cells
      subjected to strains of 0.24 and 0.27 had an increased rate of cell division (108
      and 83% increase, respectively, compared with control; p < 0.001) and DNA
      synthesis (39 and 172% increase, respectively, compared with control; p < 0.001
      for 0.27) on day 3 when compared with control cells. The results indicate that
      endothelial cells respond to various physiologic levels of cyclic load in a
      biphasic manner to initiate DNA synthesis and cell division. These data suggest
      that endothelial cell mitogenesis may be modulated by specific levels of cyclic
      load.

PMID- 9546944
TI  - Effect of felodipine on regional blood supply and collateral vascular resistance
      in patients with peripheral arterial occlusive disease.
AB  - This double-blinded, randomized, placebo-controlled study was designed to
      investigate the acute effect of felodipine on regional blood supply and
      collateral vascular resistance in patients with peripheral arterial occlusive
      disease (PAOD). Thirty men with PAOD were treated with a single dose of 5 mg
      felodipine or placebo. Systolic blood pressure (SBP), Doppler ankle pressure
      (DAP), calf blood flow (CBF) by venous occlusion plethysmography and calf
      transcutaneous oxygen tension (tcpO2) were measured during a cycle ergometry.
      Felodipine reduced SBP significantly (from 149 to 136 mmHg, p < 0.05), while
      placebo did not. DAP increased slightly but not significantly in both groups. The
      pressure gradient between SBP and DAP fell significantly in the felodipine group
      (60 vs 39 mmHg, p < 0.01) but not in the placebo group (59 vs 56 mmHg). There was
      a trend for lower velocity in tcpO2 decrease during the stress test and higher
      velocity of tcpO2 increase during recovery from exercise in the felodipine group
      although the differences between both groups were not significant. In the
      felodipine group, CBF increased by 35.6% (p < 0.05) whereas it did not change in
      the placebo group. In conclusion, while lowering SBP, felodipine increased
      slightly, or at least maintained, the blood supply to the calves in PAOD
      patients, which probably results from reducing collateral vascular resistance.

PMID- 9546946
TI  - Cost-effective strategies for the management of vascular disease.
AB  - Cardiovascular disease accounts for over 950,000 deaths and an estimated $151
      billion in direct and indirect costs. Because of this escalating clinical and
      financial burden, economic analysis has become essential for the evaluation of
      preventative therapies for vascular disease. Economic analysis compares competing
      interventions or management strategies for costs and benefits; more specifically,
      cost-effectiveness analysis compares cost in financial terms like dollars to
      measures of effectiveness like years of life saved. Important concepts in the
      creation of a valid cost-effectiveness analysis include perspective, time
      horizon, measurement of costs and effectiveness and sensitivity analysis. In
      patients with peripheral arterial occlusive disease, most morbidity and mortality
      arises from complications of coronary artery disease. Because coronary artery
      disease and peripheral arterial occlusive disease commonly occur together and
      share risk factors, pathophysiology and response to preventative therapy,
      economic evaluations of preventative therapies for coronary artery disease have
      relevance for patients with vascular disease. Cost-effectiveness analysis reveals
      that modification of vascular risk factors like tobacco use, hypertension and
      hypercholesterolemia improve clinical outcomes at acceptable cost-effectiveness
      ratios, usually less than $20,000 per year of life saved. More importantly,
      interventions like smoking cessation or lipid modification in high-risk groups
      may be cost saving, with treatment costs outweighed by financial benefits. From
      the patient, clinician and societal perspective, cost-effectiveness analysis
      supports the aggressive modification of cardiovascular risk factors in patients
      with peripheral arterial occlusive disease.

PMID- 9546947
TI  - The endothelin system in cardiovascular physiology and pathophysiology.
AB  - Endothelin-1, a member of a novel family of regulatory peptides, is the most
      potent vasoconstrictor and pressor substance known. Endothelin-1 is a 21-amino
      acid endothelium-derived peptide causing uniquely sustained vasoconstriction. In
      addition, endothelin-1 has pronounced effects on the coronary, renal and cerebral
      circulations, enhances responses to other vasoconstrictors, and is comitogenic.
      Recent studies have shown that the endothelins are essential for normal fetal
      development, and that endothelin-1 plays an important physiological role in the
      regulation of basal vascular tone and blood pressure in healthy humans. There is
      now also a wealth of evidence suggesting that endothelin-1 is a key mediator in a
      range of cardiovascular diseases associated with sustained vasoconstriction, such
      as chronic heart failure, and with vasospasm, such as subarachnoid haemorrhage.
      In addition, endothelin-1 appears to act in opposition to nitric oxide to promote
      the atherosclerotic process. There are a large number of oral and intravenously
      active endothelin antagonists entering clinical development and a number of
      clinical studies, particularly with endothelin receptor antagonists, are now
      under way. Such studies are beginning to define the role of the endothelins in
      cardiovascular disease and to confirm the potential of the endothelin system as
      an important new therapeutic target.

PMID- 9546948
TI  - Physiologic aspects of drug therapy and large artery elastic properties.
AB  - Vasoactive drugs alter smooth muscle tone not only in arterial resistance
      vessels, but also in large conduit arteries. The resultant changes in smooth
      muscle tone alter both conduit vessel size and stiffness and hence influence
      pulsatile components of left ventricular afterload. The effects of smooth muscle
      relaxation and contraction on arterial elastic properties are complex and have
      not been fully characterized. Several recent studies have utilized a new
      intravascular ultrasound technique to study the effects of changes in smooth
      muscle tone on brachial artery elastic mechanics in normal human subjects in
      vivo. Smooth muscle relaxation with nitroglycerin improves isobaric brachial
      artery compliance without significantly altering arterial wall stiffness as
      measured by incremental elastic modulus (Einc). The improvement in compliance
      with smooth muscle relaxation is the net result of factors that: (1) increase
      wall stiffness (increased tension in parallel elastin and collagen fibers); (2)
      decrease wall stiffness (decreased tension in the smooth muscle and its
      associated series elastic component); and (3) increase vessel lumen size. Using a
      modified Maxwell model for the arterial wall, smooth muscle relaxation is also
      shown to shift the predominant elements contributing to wall stress and Einc from
      smooth muscle and the collagen fibers in series with the smooth muscle to
      collagen fibers in parallel with the smooth muscle. A better understanding of the
      mechanisms contributing to changes in arterial elastic mechanics following
      alterations in smooth muscle tone will help in developing pharmacologic therapies
      aimed at reducing pulsatile components of left ventricular afterload.

PMID- 9546949
TI  - Intravenous thrombolytic therapy in acute stroke.
AB  - The article reviews the experimental basis of thrombolytic therapy, and
      summarizes the results of the recent trials of thrombolysis. Five large clinical
      trails have evaluated intravenous thrombolytic therapy for the treatment of
      hyperacute (< 6 h) stroke. Three of these studies were negative, one was
      equivocal, and one was strongly positive. The failure of demonstrate efficacy
      definitively in four of these trials may be related to a number of methodological
      factors, including the type and dose of drug administered, the timing of drug
      administered, and the method of patient selection for treatment. The NINDS
      recombinant tissue plasminogen activator (rt-PA) study showed that thrombolytic
      therapy can be of substantial benefit when administered within 3 h of stroke
      onset using strict patient selection criteria and rt-PA is now FDA approved for
      treatment of acute stroke. However, the risk of clinically significant bleeding
      is elevated. To achieve the favorable risk/benefit ratio demonstrated in the
      NINDS trial, patients must be screened by experienced clinicians for
      contraindications to thrombolysis and the acute computerized tomography (CT)
      brain scan must be carefully evaluated for radiographic features that increase
      the risk of cerebral hemorrhage. Guidelines for the use of rt-PA are provided, as
      well as insights into future thrombolytic treatment strategies.

PMID- 9546950
TI  - Thromboangiitis obliterans (Buerger's disease).
AB  - Thromboangiitis obliterans (TAO) is a nonatherosclerotic segmental inflammatory
      obliterative disease that most commonly affects the small- and medium-sized
      arteries and veins in both upper and lower extremities. In the past, TAO was
      exclusively a disease confined to men; however, recently more women have been
      diagnosed with TAO. Most patients are heavy users of tobacco, and usually
      cigarette smokers.

PMID- 9546951
TI  - Radial artery compliance in patients with peripheral vascular disease.
AB  - Compliance in largely central arteries of patients with peripheral vascular
      disease (PVD) has been reported to be reduced. However, the arterial tree is an
      inhomogeneous system, and there remains uncertainty about whether the peripheral
      arteries (e.g. the medium-sized muscular radial artery) undergo a similar change
      to the central arteries. The aim of this study was to investigate the radial
      artery elasticity in 19 patients with PVD compared with 18 normal subjects of
      comparable age and sex. Using a noninvasive high-resolution echo-tracking device
      coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial
      diameter and finger blood pressure monitoring, we measured the radial artery
      compliance by determining the diameter-pressure, compliance-pressure and
      distensibility-pressure curves. The results showed that the diameter of the
      radial artery was similar in the two groups, but that the compliance and
      distensibility were not further reduced in patients with PVD than in the normal
      controls at 100 mmHg and for a common blood pressure range. The present studies
      demonstrate that in patients with PVD the radial arterial compliance is not
      reduced, which indicates that the change in arterial elasticity is not identical.
      The potential mechanisms involved in this change in radial artery compliance are
      discussed.

PMID- 9546952
TI  - Role of endothelial cells in allograft rejection.
AB  - The immunological properties of endothelial cells suggest they perform a pivotal
      role in acute and chronic rejection following solid organ transplantation. Their
      constitutive expression of MHC class II molecules (which initiate allograft
      rejection by activating CD4 T cells) and accessory molecules allows them to
      present foreign antigen by both the direct and indirect route to the recipient's
      immune system. The costimulatory molecules used by endothelial cells appear to
      differ from those used by traditional antigen-presenting cells such as B cells
      and dendritic cells. Release of non-HLA antigens from damaged endothelial cells
      results in a chronic antibody response--possibly contributing to graft
      vasculopathy and chronic rejection. Further understanding of the factors that
      regulate MHC class II and accessory molecule expression on endothelial cells
      could lead to novel strategies of therapeutic intervention.

PMID- 9546953
TI  - Fibrinogen and cardiovascular risk.
AB  - The hypothesis that fibrinogen is closely related to cardiovascular risk has been
      strengthened through the results of various lines of research, which this review
      will aim to unravel. Several prospective epidemiological studies convincingly
      show elevated fibrinogen to represent a major, independent cardiovascular risk
      factor. Cross-sectional studies strongly associate fibrinogen and conventional
      cardiovascular risk factors. Clinical cohort studies demonstrate that increased
      fibrinogen is also a risk factor for the sequelae of cardiovascular disease. Our
      knowledge about the determinants of the variable plasma level of fibrinogen in
      health and disease is incomplete. Understanding of the mechanisms that might be
      involved in the atherothrombogenic action of fibrinogen is also fragmentary.
      Fibrinogen strongly affects blood coagulation, blood rheology and platelet
      aggregation. In addition, it has direct effects on the vascular wall and is a
      prominent acute phase reactant. All of these phenomena might constitute
      pathophysiological mechanisms involved in the association between fibrinogen and
      cardiovascular events. Their relative importance is unclear at present. Even
      though many crucial questions await conclusive answers, little doubt exists that
      fibrinogen represents a major, independent risk factor.

PMID- 9546954
TI  - The challenge and importance of defining critical limb ischemia.
AB  - Patients with critical limb ischemia are at risk of limb loss and have very high
      cardiovascular and total mortality rates, which are greater than can be accounted
      for by the usual risk factors for atherosclerosis. A definition of critical
      ischemia is necessary to determine the natural history of the disease and to
      assess and compare the efficacy of various forms of therapy. The definition needs
      to be based on hemodynamic criteria because clinical manifestations and outcomes
      are not reliable. The reasons for the difficulties in arriving at a generally
      acceptable definition are explored. Building on the previous work of others,
      modified hemodynamic definitions for critical and subcritical ischemia, which
      include measurements of pressures and of indices of microcirculation, are
      proposed.

PMID- 9546955
TI  - Development of vascular complications in diabetes.
AB  - Chronic complications of diabetes are dominated by disorders of the vascular
      system. They are a much larger burden on both diabetic patients and overall
      medical costs than diabetes itself. Large vessel problems are far more frequent
      than microvascular disorders. Loss of arterial elasticity alters arterial flow
      patterns and increases microcirculatory peak flow rates. Hyperglycemia may
      directly disrupt elastin formation. Diabetic leg artery disease may be generated
      by nerve damage, reversing this interactive contribution sequence. The major
      anatomic feature of microangiopathy in long-term diabetes is an unevenly
      distributed thickening of the intima of smaller arterioles. The thickening is
      primarily due to accumulation of type IV (basement membrane) collagen. Arterioles
      change local vessel diameter to adjust blood distribution to meet current needs.
      The thickening compromises the maximum local blood flow that may be achieved by
      this means. Compromise of maximal arteriolar dilatation does not disrupt
      exercising muscle but in the kidney, retina, and possibly in nerve, local
      circumstances can generate serious damage. Each of these system's responses has
      unique features that mediate its vulnerability, but all these organs show
      arteriolar hyalinization. The increased arteriolar accumulation of type IV
      collagen appears to be a response to the tangential force generated by flow over
      local endothelial cells. An increase in peak arteriolar wall force is mediated by
      a diabetes-specific doubling of erythrocyte membrane curvature change resistance.
      Red cell aggregation rate determines the rate of damage. The same nonspecific
      burden may also predispose to heart disease and stroke. Intensive metabolic
      control improves red cell deformability and protects against arteriolar damage.
      Therapies that address the rheologic problem more directly may add to the
      effectiveness of good diabetes control in the future.

PMID- 9546956
TI  - A case of scurvy rarely encountered in Japan.
AB  - We report a case of scurvy, which is rarely encountered in Japan. A 75-year-old
      male was hospitalized with diffuse subcutaneous hemorrhaging of both feet, pain
      on walking, and shortness of breath. A remarkably low serum level of vitamin C
      was confirmed. Administration of ascorbic acid dramatically improved his clinical
      symptoms. Improvement paralleled the increase of serum vitamin C level. This case
      underscores the important role of vitamin C on the integrity function of the
      vessel wall.

PMID- 9546957
TI  - Exercise testing and exercise rehabilitation for patients with peripheral
      arterial disease: status in 1997.
AB  - Intermittent claudication is a common manifestation of peripheral arterial
      occlusive disease (PAOD). Patients with claudication are limited in terms of
      work, housework and leisure activities so that functional status is very
      impaired. Therefore, the goals for treatment should focus on improving the
      functional impairment as well as on modifying risk factors. Evaluation of the
      functional status is of critical importance before beginning any therapy so that
      any resultant changes can be assessed. A validated graded treadmill protocol and
      validated questionnaires are used for this purpose. Three questionnaires that are
      currently used include the Walking Impairment Questionnaire, the PAOD Physical
      Activity Recall and the Medical Outcomes Study SF-36. Exercise rehabilitation is
      a method that has been particularly efficacious for treating the functional
      impairment associated with intermittent claudication. Exercise rehabilitation has
      been shown to improve pain-free treadmill walking distance by 44% to 300% and
      absolute walking distance by 25% to 442%. In addition, improvements have also
      been reported (using questionnaire data) in the ability to walk distances and
      speeds, in amount of habitual physical activity and in physical functioning.
      Thus, exercise rehabilitation has caused improvements not only in exercise
      capacity but also in community-based functional status. Because of the benefits
      of this treatment, in addition to the low associated morbidity, exercise therapy
      is recommended as an important treatment option for people with intermittent
      claudication due to PAOD.

PMID- 9546958
TI  - Images in vascular medicine. Internal iliac artery aneurysm.

PMID- 9546959
TI  - Carnitines increase plasma levels of adenosine and ATP in humans.
AB  - In order to help to clarify the mode of action of carnitine derivatives, plasma
      levels of adenosine, ATP and inosine were evaluated following the infusion of
      0.75, 0.50 and 0.25 mg/kg/min propionyl-L-carnitine (PLC) for 30 min in patients
      affected with peripheral arterial disease. Moreover, the effects of 0.75
      mg/kg/min acetyl-L-carnitine (ALC) and L-carnitine (LC) were studied in the same
      conditions. Finally, the activity of 7.5 mg/kg/min PLC administered for 3 min was
      also evaluated. PLC and ALC produced a significant increase in plasma levels of
      adenosine and ATP, whereas LC induced less relevant changes. The administration
      of the compounds did not affect the adenosine/inosine ratio. Peak plasma levels
      of adenosine preceded in any case those of ATP. The possibility can be suggested
      that the pharmacological activity of PLC, ALC, and LC may be mediated, at least
      in part, by an interference with the endogenous purine system. Since these
      effects may be related to physiological mechanisms of tissue protection, new
      pharmacological perspectives for the compounds may arise.

PMID- 9546961
TI  - Noninvasive assessment of endothelium-dependent flow-mediated dilation of the
      brachial artery.
AB  - Coronary atherosclerosis is characterized by an early loss of endothelium
      dependent vasodilation. However, the methods of assessing coronary endothelial
      function are invasive and difficult to repeat over time. Recently, a noninvasive
      ultrasound method has been widely used to measure flow-mediated dilation in the
      brachial artery as a surrogate test for endothelial function. We seek to further
      validate this method of measuring vascular function. The brachial artery
      diameters and blood flow of 20 normal volunteers (10 males and 10 females) were
      measured using high resolution (7.5 MHz) ultrasound and strain gauge
      plethysmography. Flow-mediated endothelium-dependent vasodilation was measured in
      the brachial artery during reactive hyperemia after 5 minutes of cuff occlusion
      in the upper arm. The brachial artery diameter increased maximally by 9.7 +/-
      4.3% from baseline at 1 min after cuff release and blood flow increased by 1002
      +/- 376%. Five min of cuff occlusion was sufficient to achieve 97 +/- 6% of
      maximal brachial artery dilation and degree of dilation was not different whether
      the cuff was inflated proximally or distally to the image site. The intraobserver
      variability in measuring brachial diameters was 2.9% and the variability of the
      hyperemic response was 1.4%. In young, healthy men and women, the baseline
      brachial artery diameter was the only factor that was predictive of the flow
      mediated vasodilation response. The brachial noninvasive technique has been
      further validated by the determination of flow-mediated dilation. This method of
      assessing endothelial function may help to determine the importance of
      vasodilator dysfunction as a risk factor in the development of atherosclerosis.

PMID- 9546960
TI  - Cutaneous vascular responses to acetylcholine are mediated by a prostanoid
      dependent mechanism in man.
AB  - Approximately 50% of the forearm vasodilatation to intra-arterial infusions of
      acetylcholine is mediated by endothelium-derived nitric oxide. These conclusions
      have been derived from venous occlusion plethysmographic measurements of total
      forearm blood flow during co-infusions of acetylcholine and NG-monomethyl-L
      arginine (L-NMMA), an inhibitor of nitric oxide synthase. Since venous occlusion
      plethysmography measures total limb blood flow, the relative proportion of the
      measurement from skin cannot be determined precisely. To determine the effects of
      acetylcholine on skin specifically, we have used laser Doppler flowmetry to
      measure vascular responses to local iontophoresis of acetylcholine in the forearm
      of normal male volunteers. To elucidate the possible mechanisms of cutaneous
      vasodilatation to acetylcholine, vascular responses were measured before and
      after systemic inhibition of prostanoid production and nitric oxide synthesis by
      oral aspirin (600 mg daily for 3 days) and intravenous L-NMMA (3 mg/kg for 60
      min), respectively. After aspirin administration, dose-dependent vascular
      responses to acetylcholine were reduced significantly by approximately 53% (p <
      0.005, ANOVA). In contrast, intravenous L-NMMA appeared to have no significant
      effect on cutaneous vascular responses to acetylcholine. While the role of nitric
      oxide is uncertain, vasodilatation to acetylcholine in the forearm skin is
      mediated largely by a prostanoid-dependent mechanism. Assessment of cutaneous
      vascular responses to iontophoresis of acetylcholine may, therefore, be useful in
      diseases where abnormal endothelium-dependent prostanoid function has been
      implicated.

PMID- 9546962
TI  - Comparison of graded versus constant treadmill test protocols for quantifying
      intermittent claudication.
AB  - The standard method for quantifying the symptoms of intermittent claudication is
      by using treadmill walking distance. It has recently been suggested that a graded
      exercise test is much more reproducible than a constant load exercise test.
      Graded protocols have also been claimed to abolish the placebo effect that has
      been reported with the constant load test. The reproducibility of absolute
      claudication distance (ACD) and initial claudication distance (ICD) using a
      constant load was compared to the graded load treadmill protocol. Fourteen
      patients (mean age 66 years) with varying severity of stable intermittent
      claudication were tested using a constant load (3.2 km/h, 10% gradient) and a
      graded load (3.2 km/h, 0% gradient increasing by 3.5% every 3 min). Patients were
      tested twice using each protocol in a random sequence, with a minimum 2 day
      interval between visits. Intra-class correlation coefficient (R) with a constant
      load protocol for ICD and ACD was R = 0.68, R = 0.93, respectively. With a graded
      protocol R = 0.84 for ICD and R = 0.98 for ACD. Relative coefficient of
      repeatability for ICD and ACD during constant load tests were 1.47 and 1.90
      respectively and with a graded load test were 1.69 and 1.52 respectively. It was
      concluded that the graded load test was more reproducible than the constant load
      test but only by a small margin, whilst ACD was much more reproducible than ICD
      using either protocol.

PMID- 9546963
TI  - Thoracic aortic aneurysm repair with endovascular stent-grafts.
AB  - The purpose of the study was to describe the clinical experience is using
      endoluminal stent-grafts for the treatment of thoracic aortic aneurysms in high
      risk patients. Patients with aneurysms of the descending thoracic aorta who were
      considered high surgical risks underwent evaluation for endoluminal repair. The
      prosthesis was constructed from Z stents covered with polyester fabric using
      dimensions based upon preprocedural computed tomography scans and angiography.
      Through a femoral arteriotomy or left retroperitoneal flank incision, a 22-24 Fr
      delivery catheter was inserted and advanced through the aorta to the target site
      under fluoroscopic guidance in the operating suite. The stent-graft prosthesis
      was deployed at the site of the aneurysm. 44 patients (36 male, 8 female; mean
      age 36 years) underwent stent-graft repair for thoracic aneurysms (mean diameter
      6.3 cm). The deployment was technically successful in all cases, with complete
      aneurysm thrombosis in 88%. The 30-day perioperative mortality rate was 6.8% and
      35-month actuarial survival was 82%. There were no cases of stent migration,
      surgical conversion or intraprocedural death. Paraplegia occurred in two patients
      who underwent simultaneous surgical infrarenal aortic aneurysm repair immediately
      followed by stent-graft placement for a coexisting thoracic aneurysm. The
      conclusion was that placement of endoluminal stent-grafts for repair of thoracic
      aortic aneurysms is technically feasible in high-risk patients in whom
      conventional surgery is contraindicated. Long-term studies are needed to
      determine protection against aneurysm rupture and patient survival.

PMID- 9546964
TI  - Soluble form of selectins in blood of patients with acute myocardial infarction
      and coronary intervention.
AB  - Soluble (s) P-selectin, sE-selectin, sL-selectin and soluble intercellular
      adhesion molecule-1 (sICAM-1) levels were examined by monoclonal antibody-based
      enzyme immunoassay on serum samples taken from nine patients with acute
      myocardial infarction (AMI) and eight patients with stable angina pectoris (SAP)
      before and after the successful percutaneous transluminal coronary angioplasty
      (PTCA). In patients with acute phase of AMI, the levels (mean +/- SEM) of sP
      selectin (110 +/- 18 ng/ml) and sE-selectin (54 +/- 15 ng/ml) before PTCA, were
      significantly higher than those in the SAP group, the values being 44 +/ 27 and
      21 +/- 4 ng/ml (p < 0.05), respectively. After recanalization, the levels of sE
      selectin and sL-selectin were significantly decreased (sE-selectin 54 +/- 15 to
      42 +/- 11 ng/ml, sL-selectin 1104 +/- 106 to 891 +/- 59 ng/ml, P < 0.05,
      respectively). These findings suggest that the presence of activated and/or
      injured endothelial cells, which may be involved in the plaque disruption or
      intraluminal thrombosis in AMI region and that the inflammatory process may be
      altered after reperfusion therapy.

PMID- 9546965
TI  - Decreased ankle/brachial indices in relation to morbidity and mortality in
      patients with peripheral arterial disease.
AB  - To determine the relationship between ankle/brachial indices (ABIs) and morbidity
      and mortality in patients with peripheral arterial disease (PAD), a historical
      cohort study was performed. A total of 154 patients who had undergone noninvasive
      arterial assessment of the lower extremities in 1989 and 1990 were selected for
      this purpose. Selection criteria were age > 40 years at the time of
      investigation, a resting ABI < 0.90 and the availability of an ABI after exercise
      or arterial occlusion. Mortality and vascular events were recorded after an
      average follow-up period of 6 years. A vascular event was defined as an
      intervention because of PAD, the occurrence of a nonfatal myocardial infarction
      or stroke, a transient ischaemic attack or a coronary artery bypass graft (CABG)
      or percutaneous transluminal coronary angioplasty (PTCA) procedure. During the
      period studied, 44 patients died and 111 patients suffered a vascular event. The
      relative risk for mortality was 3.1 per 0.50 decrease of the ABI at rest (95%
      confidence interval (CI) 1.1-8.7, p = 0.03) and 2.4 per 0.50 decrease of the ABI
      after exercise or arterial occlusion (95% CI 0.9-6.4, p = 0.08). The relative
      risk for mortality or the occurrence of a vascular event was 3.3 per 0.50
      decrease of the resting ABI (95% CI 1.7-6.3, p < 0.001) and 2.5 per 0.50 decrease
      of the ABI after exercise or occlusion (95% CI 1.5-4.4, p < 0.001). After
      standardization, the prognostic power of the two types of ABIs was equivalent.
      The cumulative survival after 5 years was 63% for patients with resting ABIs <
      0.50, 71% for patients with ABIs 0.50-0.69 and 91% for those with ABIs of 0.70
      0.89. There were obvious differences between the mean initial ABIs of patients
      who suffered a vascular event and/or died and those of survivors, who did not
      suffer an event. A relatively simple measurement like the determination of the
      resting ABI can give valuable information about the prognosis for vascular
      related morbidity and mortality. This can be of help in the approach of patients
      with PAD and assist in therapeutical decision making. Determination of the ABI
      after exercise or occlusion has no additional value for this purpose.

PMID- 9546966
TI  - Oxygen uptake during constant-intensity exercise in patients with peripheral
      arterial occlusive disease.
AB  - The purpose of the present study was to evaluate the oxygen uptake (VO2) response
      to walking in patients with peripheral arterial occlusive disease (PAOD) at a
      constant velocity and to determine whether the oxygen uptake observed during
      constant-intensity exercise in this population is associated with the severity of
      PAOD. Forty-nine PAOD patients with intermittent claudication were recruited
      (values are mean +/- SD) [age = 66.4 +/- 8.0 years, weight = 83.3 +/- 16.0 kg,
      body mass index = 28.8 +/- 5.6, ankle/brachial systolic blood pressure index
      (ABI) = 0.63 +/- 0.18, VO2peak = 13.02 +/- 2.99 ml/kg/min]. Patients were
      evaluated during a 2.0 miles/h walk on a treadmill until maximal claudication
      pain or for a maximum of 20 minutes. On average, patients walked for a duration
      of 10.3 +/- 5.8 min. Despite the constant absolute intensity during the exercise
      bout, there was a significant (p < 0.01) 4.0% increase in VO2 from min 3 of
      exercise (10.58 +/- 2.02 ml/kg/min) to min 5 (11.01 +/- 2.18 ml/kg/min) and a
      further 4.0% increase from min 5 to the end of exercise (11.46 +/- 2.32
      ml/kg/min). Expressed as relative exercise intensity, this represented an
      increase from 80.8 +/- 18.3% to 87.1 +/- 18.0% of VO2peak from min 3 to the end
      of exercise. The magnitude of increase in VO2 during the exercise bout was not
      correlated with resting ABI (r = 0.00, p = 0.68) or post-exercise ABI (r = 0.04,
      p = 0.73). There was a nonsignificant trend towards a correlation between the
      time to onset of claudication pain and the magnitude of increase in VO2 (r =
      0.25, p = 0.08). Results of this study suggest that an increase in VO2 occurs
      during constant-velocity walking at a high relative intensity in PAOD patients.
      This increase in VO2 does not appear to be related to the severity of PAOD.

PMID- 9546967
TI  - Mechanisms of neointima formation--lessons from experimental models.
AB  - The lamina intima of an artery is the region between the endothelial cell surface
      and the internal elastic lamina, which forms the luminal margin of the media. In
      humans the intima of atherosclerosis-prone arteries becomes thicker due to
      accumulation of smooth muscle cells, which originate from the media. The
      introduction of percutaneous transluminal coronary angioplasty (PTCA) boosted
      scientific interest in intimal thickening, because restenosis remains an
      unresolved problem of this intervention. In order to unravel the mechanisms of
      intimal thickening there is a need for appropriate animal models. A brief
      overview of these models is given together with factors that control
      proliferation and/or migration. Despite intensive research on neointima
      formation, an effective therapy for restenosis has not emerged to date. This may
      be due to the fact that other processes, such as acute elastic recoil and chronic
      constrictive remodeling may contribute to lumen narrowing as well. Other
      limitations of neointima models are related to species and anatomical
      differences. Most studies are performed in arteries that are either lesion-free,
      or contain relatively mild plaques, in contrast to the complicated, stenotic
      lesions that are the substrate for human PTCA. Other differences are the severity
      of the injury and incorporation of a mural fibrin-rich thrombus. Nevertheless,
      studies based on superficial injury, like the frequently used balloon denudation
      model, are useful. There are similarities with angioplasty, such as endothelial
      cell damage and proliferation of medial and intimal smooth muscle cells. The use
      of techniques such as differential display, gene transfer and application of
      antisense oligonucleotides may provide new therapeutic approaches to reduce
      neointima formation.

PMID- 9546968
TI  - New developments in nitrosovasodilator therapy.
AB  - Under basal conditions, nitric oxide (NO) modulates vascular tone, serves as an
      antithrombotic agent, and inhibits vascular smooth muscle cell proliferation. NO
      deficiency has been implicated in the pathophysiology of several vascular
      disorders, including hypertension, atherosclerosis, and restenosis, and provides
      a plausible biologic basis for the use of NO replacement therapy in these
      conditions. Treatment with conventional nitrate preparations is limited by a
      short therapeutic half-life, systemic absorption with potentially adverse
      hemodynamic effects, and drug tolerance. To overcome these limitations, novel
      delivery systems and novel NO donors have been developed that offer selective
      effects, a prolonged half-life, and a reduced incidence of tolerance.

PMID- 9546969
TI  - The microcirculation in venous hypertension.
AB  - Venous ulceration is a common problem in western countries and results in large
      costs to healthcare systems. A number of hypotheses of the mechanisms of
      development of venous ulceration have been advanced, but this question has not
      been fully resolved. In recent years research effort has focused on the
      microcirculation of the skin and many methods of investigation have been employed
      to study this. Some of the principal findings described in published work are
      reviewed in this article. It seems unlikely from the available evidence that
      venous ulceration is attributable solely to failure of diffusion of oxygen and
      other small nutritional molecules to the tissues of the skin. The microvascular
      changes in the skin are characterised by activated endothelium and perivascular
      inflammatory cells. It is much more likely that leucocytes attach themselves to
      the cutaneous microcirculation, become activated and produce endothelial injury.
      Repeated over many months or years, this chronic inflammatory process leads to be
      tissues changes of lipodermatosclerosis. Although there is evidence of leucocyte
      involvement in the pathogenesis of venous ulceration, the exact mechanisms remain
      to be resolved. Improved treatment for patients may be devised once a better
      understanding of the basic causes of this condition has been reached.

PMID- 9546970
TI  - Images in vascular medicine. Incomplete (latent) subclavian steal syndrome.

PMID- 9546971
TI  - The epidemiology of peripheral arterial disease: importance of identifying the
      population at risk.
AB  - Data from the Framingham Study and other population studies indicate that
      intermittent claudication (IC) sharply increases in late middle age and is
      somewhat higher among men than women. Noninvasive testing in populations
      indicates that the true prevalence of peripheral arterial disease (PAD) is at
      least five times higher than would be expected based on the reported prevalence
      of IC. Peripheral arterial disease correlates most strongly with cigarette
      smoking and either diabetes or impaired glucose tolerance. Other risk factors for
      PAD include hypertension; low levels of high-density lipoprotein cholesterol; and
      high levels of triglycerides, apolipoprotein B, lipoprotein(a), homocysteine,
      fibrinogen and blood viscosity. Individuals with PAD are more likely to have
      coronary heart disease and cerebrovascular disease than those without PAD.
      Because of the high risk of both nonfatal and fatal cardiovascular disease (CVD)
      events in PAD patients, individuals with evidence of PAD should undergo both a
      careful examination of the entire cardiovascular system and aggressive
      modification of CVD risk factors.

PMID- 9546972
TI  - The pathophysiology of peripheral arterial disease: rational targets for drug
      intervention.
AB  - The most common cause of peripheral arterial disease (PAD) is atherosclerosis,
      which begins with an alteration in endothelial biology due to
      hypercholesterolemia, diabetes mellitus, hypertension, tobacco use, elevated
      levels of lipoprotein(a) or homocystinemia. With chronic and severe arterial
      disease, changes begin to occur in the microcirculation, including obstruction at
      the microvascular level and tissue injury. Based on insights into the vascular
      biology of PAD, new therapies have been developed and are at various stages of
      clinical trials. Future pharmacotherapy for PAD will include agents that have one
      or more of the following attributes; (1) reduce, or even reverse, the progression
      of atherosclerosis; (2) inhibit plaque rupture; (3) inhibit thrombosis by a novel
      mechanism; (4) induce angiogenesis; (5) reverse microvascular derangements; (6)
      affect blood rheology; and (7) enhance skeletal muscle's ability to use available
      nutrients.

PMID- 9546973
TI  - Clinical assessment of the patient with claudication: the role of the vascular
      laboratory.
AB  - The noninvasive vascular laboratory aids in the evaluation of patients with
      peripheral arterial disease (PAD). Several qualitative and quantitative
      noninvasive tests are useful for diagnosing PAD and monitoring patients' response
      to treatment. These tests include Doppler ultrasonography, pulse volume
      recording, segmental blood pressure measurement, exercise testing, post-occlusive
      reactive hyperemia testing, transcutaneous oximetry and color-assisted ultrasound
      imaging. Each test has specific utility and can be used either individually or in
      combination with other noninvasive tests to obtain information about the
      hemodynamic and functional severity of peripheral atherosclerosis in patients
      with claudication.

PMID- 9546974
TI  - Exercise in the treatment of claudication: assessment and treatment of functional
      impairment.
AB  - Claudication is an important cause of impaired exercise capacity, which limits a
      patient's ability to walk and thus to meet the personal, social and occupational
      demands of daily life. Given that improvement of the walking impairment is the
      primary goal of treating claudication, exercise performance and functional status
      of patients with claudication should be measured before and after any
      intervention. Assessment of functional status in both the laboratory and
      community settings is important so that the various treatments can be judged as
      to relative efficacy. Studies have shown that exercise training programs have a
      clinically important impact on functional capacity in persons with claudication.
      A meta-analysis showed that pain-free walking time increased 180% and maximal
      walking time increased 120% in claudicants who participated in an exercise
      program. Substantial improvements have been found in walking speeds and distances
      (65% and 44%, respectively), caloric expenditure (31%) and physical functioning
      (67%).

PMID- 9546975
TI  - The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the
      treatment of peripheral arterial disease.
AB  - Despite the widely held belief that there are no effective medical therapies for
      peripheral arterial disease (PAD), current data suggest that medical therapies
      can effectively modify the natural history of atherosclerotic lower extremity
      arterial occlusive disease. The ideal medical therapy would improve claudication,
      forestall the onset of limb-threatening events, decrease rates of invasive
      interventional therapies and improve long-term patient survival. These ideal
      outcomes might be achieved through the use of smoking cessation interventions,
      including behavioral and pharmacological therapy, and the administration of
      antiplatelet and lipid-lowering medications in patients with PAD.

PMID- 9546976
TI  - Role of revascularization in the treatment of claudication.
AB  - Intermittent claudication is a relative indication for vascular reconstruction.
      Conservative management with a combination of risk factor control, exercise
      training and medical therapy will relieve or at least improve claudication in
      some patients. If claudication precludes gainful employment or imposes an
      unacceptable alteration in lifestyle, surgical revascularization should be
      considered. Surgical bypass for claudication will produce optimal results in
      younger patients, in whom near-normalization of the ankle/brachial index can be
      anticipated. Proximal axial (in-line) reconstructions maintain their patencies
      longer than more distal, and often technically more challenging, bypasses. These
      tenets also apply well to percutaneous transluminal angioplasty. Both surgical
      and catheter-based interventions carry potential risks of short- and long-term
      morbidity, although overall morbidity associated with surgery for claudication is
      acceptably low. Interventions are justified only if they are safe, effective and
      durable, and if they are performed after the long-term prognosis for both life
      and limb is considered.

PMID- 9546977
TI  - Current and future drug therapies for claudication.
AB  - The primary objectives of claudication treatment are to reduce cardiovascular
      mortality and improve walking ability. Patients with claudication have 60%
      mortality over 10 years, with most deaths due to myocardial infarction and
      stroke. Aggressive risk-factor modification is required in all these patients,
      particularly smoking cessation, lipid modification, and treatment of
      hypertension, diabetes and elevated homocysteine levels. Aspirin, ticlopidine and
      clopidogrel are all effective in reducing the risk of myocardial infarction,
      stroke and vascular death, and thus antiplatelet therapy should be considered in
      all claudicants. Patients with disabling claudication should be considered for
      therapies that relieve claudication pain and improve exercise performance, the
      most effective being exercise training and smoking cessation. Pentoxifylline, the
      only approved claudication drug in the United States, has modest efficacy in
      improving treadmill exercise performance. Other drugs shown to be of some benefit
      in patients with claudication include propionyl-L-carnitine, cilostazol and
      possibly prostaglandin derivatives. Several antiplatelet agents and angiogenic
      growth factors are also being evaluated for the treatment of claudication.

PMID- 9546978
TI  - Clinical use of intravascular ultrasound.
AB  - Intravascular ultrasound has dramatically changed our view of atherosclerotic
      disease and has helped to define mechanisms of therapeutic interventions,
      providing a new rationale for selection of appropriate devices. Currently, this
      technology is used for sizing and orientation of commonly performed interventions
      such as balloon angioplasty and directional atherectomy. The information from
      intravascular ultrasound has also led to a dramatic change in the deployment
      algorithm of stents. Further improvements in catheter design and the findings
      from clinical trials utilizing intravascular ultrasound will help define a
      practical role for this new technology.

PMID- 9546979
TI  - Application of intravascular ultrasound in remodelling studies.
AB  - Arterial remodelling is an important determinant of luminal narrowing in de novo
      atherosclerosis as well as in restenosis following balloon angioplasty. To date,
      intravascular ultrasound is the best diagnostic modality to study changes in
      arterial size in vivo. The role of arterial wall remodelling in de novo
      atherosclerosis and restenosis has been well established by intravascular
      ultrasound studies. Single intravascular ultrasound studies have demonstrated
      that the artery may enlarge, fail to enlarge or even shrink if plaque
      accumulates. In restenosis studies, serial intravascular ultrasound studies have
      allowed examination of the remodelling process over time and have shown that
      arterial shrinkage and not intimal hyperplasia is the predominant factor
      responsible for luminal narrowing after balloon angioplasty. This article will
      focus on the applicability of intravascular ultrasound to the study of vascular
      remodelling in de novo atherosclerosis, in restenosis after balloon angioplasty,
      atherectomy and stenting, in saphenous vein grafts and in the coronary arteries
      of transplanted hearts.

PMID- 9546980
TI  - The latest in electronic imaging.
AB  - Development of new transducer and system technologies has led to major advances
      in image quality for electronic imaging catheters. New, 64-element arrays have
      increased sensitivity and optimized image resolution. System technology has
      advanced to include high speed reconstruction using 'complete data sets' of
      information. The incorporation of personal computer technology has enabled new
      user interfaces and digital image archiving. New, combined imaging and therapy
      catheters allow for efficient usage of devices. The debut of intravascular colour
      flow imaging technology promises a new dimension in the treatment of coronary
      artery disease.

PMID- 9546981
TI  - Quantitative three-dimensional intravascular ultrasound.
AB  - Three-dimensional (3-D) intravascular ultrasound (IVUS) allows for the
      visualization of entire coronary segments, provides more detailed insights into
      the geometry of atherosclerotic plaques and facilitates serial studies. Automated
      quantitative 3-D IVUS methods reduce the analysis time and the subjectivity of
      boundary tracing, and permit complex IVUS studies. The 3-D IVUS approach is not
      restricted to research applications, but may be used as a valuable clinical tool.
      Evaluation of the coronary segment of interest before catheter-based coronary
      interventions provides information which may facilitate the selection of
      interventional devices. Moreover, 3-D IVUS allows for a careful assessment of the
      procedural results and potential post-procedural complications. ECG-gated image
      acquisition, automated contour detection, and approaches using data of both 3-D
      IVUS and biplane angiography represent the recent progress in this field. Three
      dimensional IVUS will surely gain further importance and become a routine
      technique, if the interest and research effort is sustained.

PMID- 9546982
TI  - High-frequency intracoronary ultrasound imaging.
AB  - Intravascular ultrasound is playing an increasingly important role in the
      clinical management of coronary interventions. In the past few years the
      technology for intracoronary ultrasound, in response to clinical pressure, has
      moved towards lower profile probes with improved handling. While new catheter
      designs are markedly improved on their predecessors, image quality has not seen
      significant gains due to the primitive nature of the ultrasound transducer
      designs. In this article, the potential for improving image quality by increasing
      the frequency and focusing the ultrasound beam is explored. Basic aspects of
      transducer implementation are discussed and the acoustic properties of vascular
      tissues and blood are reviewed. A variety of instruments are used to image
      coronary and femoral arteries at frequencies ranging from 40 to 200 MHz. These
      studies serve to illustrate the trade-offs in the development of high frequency
      IVUS systems. There would appear to be no fundamental reason why frequencies in
      excess of 50 MHz could not be implemented. Studies using prototype IVUS
      instruments in the 50 MHz range demonstrate significant improvements in image
      quality.

PMID- 9546983
TI  - True reconstruction of vessel geometry from combined X-ray angiographic and
      intracoronary ultrasound data.
AB  - At present a rapidly expanding variety of methods appear to provide three
      dimensional (3-D) reconstructions of blood vessels in a patient. Generally the
      results of such methods look very realistic. However, only a few produce a true 3
      D reconstruction. We strongly suggest that for a true 3-D reconstruction of a
      blood vessel the following criteria should at least be fulfilled: (1) the
      arterial wall rather than the lumen must be reconstructed; (2) the spatially
      curved course of the vessel must be included; and (3) the orientation of local
      vessel wall characteristics, for example, plaque eccentricity, with respect to
      the luminal course must be correctly maintained. Currently, only methods
      combining biplane X-ray angiography and intravascular ultrasound imaging (IVUS)
      have succeeded in providing true 3-D reconstruction of a segment of a vessel.
      Accuracy of those reconstructions is derived from studies using phantoms having
      precisely known geometry. In patients, data on accuracy are more difficult to
      obtain. Nevertheless, a comparison can be made between the actual length of an
      IVUS pull-back trajectory and its reconstructed length showing relative
      differences of less than 3%. Further knowledge can be obtained by comparing
      simulated angiograms derived from the 3-D reconstruction with the real contrast
      angiograms. True 3-D reconstruction methods of the vessel wall and lumen,
      applicable in the individual patient, have become feasible and produce accurate
      results. Application of such a method will be helpful to understand immediate and
      long-term vessel remodelling induced by all types of catheter interventions and
      in the study of progression or regression of atherosclerotic wall disease.

PMID- 9546984
TI  - Potentials of volumetric blood-flow measurement.
AB  - Current intravascular ultrasound techniques produce real-time imaging of a vessel
      cross-section with a scan plane normal to blood flow. When randomly distributed
      blood particles travel through this ultrasound imaging plane, the received echo
      signals decorrelate as a function of time. The speed of such a decorrelation
      procedure is proportional to the flow velocity. This phenomenon provides a
      potential to estimate blood velocities by means of decorrelation analysis. In
      this paper, we present a method for measuring local blood velocity and
      quantifying volume flow directly from cross-sectional intravascular ultrasound
      data. This method is based on multiple decorrelation assessments with a sequence
      of radio frequency echo signals. The velocity measurement is obtained by
      comparing the measured decorrelation value with the prior knowledge of the beam
      characteristics of an intravascular ultrasound transducer. Volume flow is derived
      by integrating the cross-sectional area and its corresponding velocity vector
      over the vessel lumen. The decorrelation-based method was tested in vitro with a
      flow phantom. Measurements were also carried out in vivo in pig experiments to
      determine the usefulness of this method in clinical settings. Preliminary results
      of these experiments indicate that the proposed decorrelation method is able to
      extract cross-sectional velocity profiles and volumetric flow both in vitro and
      in vivo.

PMID- 9546985
TI  - Intravascular elastography: principles and potentials.
AB  - Many intravascular therapeutic techniques for the treatment of significant
      atherosclerotic lesions are mechanical in nature: angioplasty, stenting and
      atherectomy. The selection of the most adequate treatment would be advantageously
      aided by knowledge of the mechanical properties of the lesion. Based on the
      success of conventional intravascular ultrasound (IVUS) imaging in accurately
      depicting the morphology of atheromatous lesions, ultrasonic tissue
      characterization has been proposed to determine the composition of
      atherosclerotic plaques. Elastography is an ultrasound-based imaging technique
      capable of producing cross-sectional elasticity images called elastograms. The
      technique involves analysis of echo signals obtained at two states of incremental
      intravascular pressure. High resolution, local tissue displacement estimation by
      cross-correlation is followed by computation of local strain. Strain is utilized
      as an indicator of the local compliance of tissue under the assumption of
      constant stress within the scan plane. Using vessel-mimicking phantoms, we
      demonstrate the feasibility of intravascular elastography experimentally. The
      elastograms are able to depict lesions of different elasticity independently of
      the echogenicity contrast, since the information provided by the elastograms is
      generally independent of that obtained from the conventional IVUS image. Thus,
      the elastogram can complement the characterization of lesions from the
      conventional IVUS image. Progress to in vitro and in vivo testing is expected in
      conjunction with ongoing improvements in the current instrumentation and
      processing.

PMID- 9546986
TI  - Technical aspects of ultrasound imaging guidewires.
AB  - In many interventional catheterization laboratories around the world the use of
      intravascular ultrasound (IVUS) has become a routine addition to the catheter
      based interventional procedures. IVUS catheters, for coronary use, typically of a
      size around 3 French, provide images that assist in diagnosing the coronary
      obstructive disease, choosing the most appropriate recanalization method,
      monitoring the recanalization process and evaluating the end result. The downside
      of the use of IVUS, apart from additional cost to the procedure, is the
      additional exchange of catheters during the procedure. Several designs of hybrid
      catheters have been proposed, combining IVUS imaging with a therapeutic de
      obstruction method in one catheter. A more modular approach is to equip the
      guidewire with imaging capability. Such a guidewire would provide an image of the
      stenotic region as well as guide the recanalization catheter to its location. It
      will, however, require further miniaturization of the ultrasound imaging
      technology, which already is scaled down considerably to enable coronary imaging.
      In addition, the ultrasound imaging guidewire (UIG) would have to possess
      specific qualities in bending and torque to act as a true guidewire. A first step
      to modularity is the separately used 'imaging core', which is advanced into the
      guidewire lumen of a therapeutic catheter, but cannot guide this catheter to the
      desired location. The combination of both imaging and mechanical requirements
      would yield a true UIG, but constitutes major technical challenges.

PMID- 9546987
TI  - First experience with imaging core wires.
AB  - This study is the first assessment of feasibility and clinical usefulness of an
      imaging wire. The device used is a 0.018" flexible cable mounting a 30 MHz
      piezoelectric crystal at the end. The only possible application of the wire in
      its current configuration is the assessment of balloon expansion with over-the
      wire balloon catheters. In this study, 17 lesions were examined in 14 patients.
      Despite careful removal of the air, no image could be obtained with the balloon
      deflated or through the shaft of conventional balloon catheters. When the balloon
      was inflated to 1-4 atm the circular echo-free cross-section of the balloon
      became visible, surrounded by the dense line of the balloon membrane and by the
      vessel wall. By examining the stent area at different balloon pressures, it was
      possible to determine the stent recoil between maximal balloon expansion and
      lowest balloon pressure allowing a readable ultrasound image. These encouraging
      preliminary observations confirm the feasibility of the use of an ultrasound
      guidewire for monitoring balloon expansion during stent implantation. After high
      pressure inflation, a moderate reduction of the stent lumen was observed during
      deflation, compatible with the small recoil predicted for the stainless-steel
      mesh stent used.

PMID- 9546988
TI  - Forward-looking catheters.
AB  - Current intravascular ultrasound catheters provide a cross-sectional view of the
      blood vessel that limits their ability to visualize severely stenosed or occluded
      vessels. Forward-looking ultrasound catheters can overcome these limitations.
      Development of a practical forward-looking ultrasound catheter requires solutions
      to address the need for improved lateral resolution and depth of penetration
      presented by the forward-looking format. Methods are also needed to generate the
      forward-looking scan within the space constraints of a catheter. New developments
      using mechanical scanning methods suggest that a practical device appears
      achievable. Two-dimensional, as well as three-dimensional imaging, may be
      possible. Early efforts towards a phased array scanner have also begun.

PMID- 9546989
TI  - Irradiation and stenting.
AB  - Intravascular irradiation by both gamma and beta sources has been shown to
      prevent neointimal proliferation after balloon injury in the overstretch pig
      coronary model. A number of clinical studies are underway that involve
      brachytherapy from gamma sources in vessels that have been stented. The purpose
      of this review is to analyse the physical nature of the interaction of various
      forms of radiation with stent materials and to summarize the available
      experimental information for relevant clinical correlates of these effects. The
      ultimate use of vascular radiation in the presence of metallic stents will
      require knowledge of the possible dose alterations, and where possible,
      techniques to compensate for these effects.

PMID- 9546990
TI  - Advantages and limitations of radioactive stents.
AB  - The concept of radioactive stents was initiated to prevent restenosis after
      angioplasty in patients with coronary artery disease. We review the modes of
      fabrication, dosimetry and the biological effects of radioactive stents.
      Radioactive stents deliver ionizing radiation continuously at very low-dose rates
      according to the half-life of the incorporated radioisotopes. The activity levels
      of radioactive stents are up to 10,000 times lower than activity levels of
      sources used for catheter-based vascular brachytherapy. Radioactive stents allow
      uniform dose distribution and precise dosimetry because of the direct source
      contact with the circumference of the vessel. Animal studies show that these
      stents can potently inhibit smooth muscle cell proliferation and neointimal
      hyperplasia. A persistent inhibition of neointimal hyperplasia appears to be dose
      dependent. Local or systemic side effects related to the irradiation were not
      observed. A limitation of radioactive stents could be the dose-dependent delay in
      stent endothelialization which, however, did not cause thrombotic vessel
      occlusion in animal experiments. Whether a delay in stent endothelialization is
      associated with an increased rate of occlusive stent thrombosis in humans
      requires further studies.

PMID- 9546991
TI  - Basis of endovascular radiation therapy in human coronary arteries.
AB  - Restenosis is the major limitation to a full expansion of all revascularization
      procedures. Elastic coil, unfavorable remodeling and a proliferative response to
      injury are the more importune mechanisms to restenosis. Ionizing radiation based
      on the inhibitory effect on cellular proliferation has been widely used in the
      treatment of numerous neoplastic and non neoplastic conditions. Experimental
      brachytherapy has demonstrated to reduce restenosis in peripheral arteries and
      coronary arteries in animal models and gamma-radiation therapy decrease
      restenosis after stent implantation in femoral-popliteal arteries in patients. We
      developed to evaluate the feasibility, safety and effects of gamma intracoronary
      radiation therapy after coronary angioplasty a protocol and used a wire 0.018 and
      0.014 inches in diameter and 30 mm active length with 192 Iridium into the closed
      channel polyethylene catheter was not centered the source within the vessel wall.
      We prescribed 25 Gy and 20 Gy to the diameter of the reference artery to 21
      patients. The 24 hours, two months and after six months angiographic follow up
      demonstrated that intracoronary radiation therapy was feasible and safe and
      preliminary analysis point out a reduction in late loss. The efficacy and safety
      of the different sources and procedures should be well established. There is a
      great expectation regarding the efficacy and safety of vascular brachytherapy to
      increasing the use of endovascular recanalization procedures.

PMID- 9546992
TI  - Physics and safety aspects of a coronary irradiation pilot study to inhibit
      restenosis using manually loaded 192Ir ribbons.
AB  - Radiation therapy has been successfully used in controlling some forms of benign
      tissue growth. A pilot study has been launched to evaluate the usefulness of
      localized radiation therapy in reducing restenosis after coronary angioplasty. In
      this randomized, double-blind study, patients with known restenosis received
      balloon angioplasty or additional stent implantation and were then randomized to
      receive either radiation or placebo treatment. Active sources consisted of 192Ir
      in the form of cylindrical seeds (0.3 x 0.05 cm). The seeds are embedded in a
      nylon ribbon. The nylon ribbon is passed through an indwelling coronary catheter.
      For this pilot trial, radioactive sources were exposed to blood elements and,
      therefore, required sterilization. A method of sterilization is described. A
      working team was developed to perform coronary radiation procedures at our
      institution. A description of the procedure is provided.

PMID- 9546994
TI  - Five year follow-up after brachytherapy for restenosis in peripheral arteries.
AB  - Restenosis in peripheral vessels caused by intimal hyperplasia after stent
      implantation, PTA, atherectomy or laser treatment ranged up to 40%. In order to
      avoid the hyperplastic reaction with restenosis we treated our patients with
      prophylactic endovascular afterloading therapy after failure of PTA in case of
      recurrent stenosis. We had 30 patients with up to 4 recurrent stenoses between 4
      and 7 months due to intimal hyperplasia in the stented area. To minimize the
      reocclusion rate we performed an irradiation with 12 Gy surface dose in one
      session using the endovascular afterloading method with 192 Iridium HDR following
      re-PTA in the stented vessel segment. The longest follow up is 68 months. The
      histological analyses of tissue years after irradiation showed a thinner, more
      compact cellular layer of the myofibroblasts with less myxoid degeneration
      between the cells compared to intimal hyperplasia and plaques in not irradiated
      vessel segments. The follow up showed a significant effect of endovascular
      radiotherapy. The histological findings after irradiation were a diminished
      growth in the cellular population of the analysed vessel wall compared to not
      irradiated vessel wall segments of the same patient. These findings may be
      explained by a reduced migration and mitosis rate of myofibroblastic cells after
      irradiation. The method may be an interesting alternative to stent implantation
      alone. Even vessel segments like the Hunter's channel will be patent for a long
      time follow up. Because of the steep decay in the dose using the endovascular
      irradiation method with 192 iridium HDR, the method can be used with minimal risk
      for the surrounding tissue.

PMID- 9546993
TI  - Feasibility and safety of beta irradiation in human coronary arteries.
AB  - We have developed a technique of endoluminally centred endovascular beta
      irradiation aimed at preventing restenosis after PTCA. The source consists of a
      pure metallic 90-Yttrium coil that can be positioned within the lumen at the
      target site by the use of a centering device and an afterloading console.
      Experimental evaluation of this approach showed that a dose of 18 Gy delivered at
      the inner arterial surface was highly effective in preventing fibrointimal
      hyperplasia in rabbit carotid and iliac arteries. A pilot clinical evaluation in
      the coronary arteries of 15 patients using the same dose demonstrated excellent
      feasibility and no unexpected side-effects. A dose-finding evaluation in the
      clinical setting is now planned.

PMID- 9546995
TI  - Clinical trial design.
AB  - Clinical trials of radiation therapy provide the first opportunity to examine a
      device therapy in a truly blinded manner. Observational studies suggest that
      moderate-sized clinical trials can adequately test the ability of the method to
      reduce restenosis. The mechanism by which such reduction is achieved should be
      studied by angiographic and intravascular ultrasound methods although clinical
      outcomes will be uniquely valuable because of the blinding.

PMID- 9546996
TI  - The vessel wall reaction in restenosis.
AB  - Coronary angioplasty imposes injury on the coronary artery during the procedure
      to achieve adequate revascularization. The arterial response to that injury is
      critical to both the acute and long-term success or failure of the procedure. As
      newer technologies become clinically available, it is increasingly evident that a
      final common response to angioplasty is neointimal formation, and adventitial
      contraction known as remodelling. Both procedures appear to occur to varying
      degrees, and similarly appear dependent on the degree of injury. Neointimal
      hyperplasia is a major factor in the restenosis problem, although others are
      clearly important. Additional factors include thrombus, intimal and medial
      dissections and elastic recoil of the arterial wall. The proportion of the
      restenosis problem caused by each is unclear, but current efforts to solve
      restenosis centre on limiting neointimal hyperplasia, the primary response to
      injury of the vessel. This paper will review arterial injury during
      revascularization in both patients and animal models, with special emphasis of
      the nature and formation of neointimal hyperplasia.

PMID- 9546997
TI  - Basic physics and biology of radiation therapy.
AB  - The therapeutic use of ionizing radiation followed shortly after the discovery of
      X-rays by Roentgen in 1895. The radiobiological principles that underlie the
      clinical use of ionizing radiation have been ablated slowly over the past
      century. Ionizing radiation, which is used therapeutically for benign and
      malignant conditions, is characterized by the localized release of large amounts
      of energy. These radiations may be electromagnetic (X- or gamma rays) or
      particulate (electrons, protons, alpha particles, neutrons, etc.). In this paper
      we will review some basic radiation physics and radiation biology principles
      which might be unfamiliar to the interventional cardiologist interested in this
      evolving application of radiation to prevent restenosis.

PMID- 9546998
TI  - Response to radiation therapy in animal restenosis models.
AB  - Intracoronary radiation therapy for prevention of restenosis is a new emerging
      technology which is tested nowadays in clinical trials. Several methods of
      radiation and a variety of isotopes have been tested in different animal models
      in order to prove the concept and to find a friendly user system for this
      application. Using the same treatment doses both gamma and beta emitters
      demonstrated similar results despite differences in isotope characteristics:
      penetration, activity, dose rate and treatment time. In addition, intracoronary
      radiation delivered via a catheter-based system prior to coronary stenting showed
      reduction of neointimal hyperplasia in the porcine coronary stent model and may
      further reduce restenosis coupled to stent implantation. The value of radioactive
      stents is also considered especially in large vessels with regard to their low
      activity and their proximity to the vessel wall. Adventitial labeling and
      immunostaining suggested the mechanism by which radiation reduces smooth muscle
      cell proliferation at the adventitia and affects on favorable vessel remodeling.
      These studies which were pioneered in this new field and have facilitated the
      clinical trials of using radiotherapy for prevention of restenosis are reviewed
      and discussed in this paper.

PMID- 9546999
TI  - The neurotoxicity of amyloid beta protein in aged primates.
AB  - Amyloid beta protein deposition is a universal feature of Alzheimer's disease
      brain. To investigate the effects of amyloid beta protein in aged primates,
      intracerebral microinjections of solubilized amyloid beta (A beta (1-40)) and
      control peptides were made into the frontal cortex of 7 primates under
      stereotactic guidance. Control injections consisted of vehicle alone, a 37 amino
      acid non toxic peptide (A37), scrambled peptide (CA4), and reverse peptide (A
      beta (40-1)). Amyloid beta peptide produced dose-dependent cortical lesions that
      were significantly larger than those produced by vehicle or by isomolar control
      peptides (3.28 and 2.20 fold larger respectively) (p = < 0.005). In 5 aged
      primates, the cortex surrounding the amyloid beta lesions contained argyrophilic,
      thioflavine S fluorescent, Alz 50 and ubiquitin immunoreactive neurons and
      perikarya. The number of Alz 50 immunoreactive neurons surrounding the amyloid
      beta injections was significantly greater (mean 127 +/- 39) than the number found
      surrounding reverse peptide injections (mean 20 +/- 13) and other control
      peptides (mean 0.8 +/- 0.3) (p < 0.05). Neuronal and neuritic alterations were
      not found adjacent to the amyloid beta peptide lesions in young monkeys and
      control injections produced insignificant Alz 50 neuronal positivity. These
      findings suggest that amyloid beta peptide is neurotoxic in primate brain and
      that the cytoskeletal response to amyloid beta protein is specific and age
      related.

PMID- 9547000
TI  - Effects of beta-amyloid peptides on the fluidity of membranes from frontal and
      parietal lobes of human brain. High potencies of A beta 1-42 and A beta 1-43.
AB  - beta-amyloid peptide (A beta) and several A beta-fragments decrease the fluidity
      of human cortex membranes in a concentration dependent fashion. The effect of A
      beta on membrane fluidity increases with peptide length, is most pronounced for A
      beta 1-43 and can be seen at concentrations as low as 100 nmol/l. While the
      fragment A beta 25-35 is active, scrambled peptide (A beta 35-25) when
      investigated under similar conditions shows no effects on membrane fluidity. The
      effect of A beta peptides on fluidity of the phospholipid bilayer is more
      pronounced in the hydrocarbon core (labeled with the fluorescence probe 1,6
      diphenylhexa-1,3,5-triene) than in the region of the hydrophilic heads (labeled
      with the fluorescence probe 1-[4'-(trimethylamino)phenyl]-6-phenylhexa-1,3,5
      triene). It is suggested that the effect of A beta on neuronal membranes is
      probably a major initial mechanism in a cascade of events finally leading to
      neurotoxicity and cell death in Alzheimer's disease.

PMID- 9547001
TI  - Laminin blocks the assembly of wild-type A beta and the Dutch variant peptide
      into Alzheimer's fibrils.
AB  - Amyloid fibril formation is believed to be a nucleation-dependent polymerization
      process which may be influenced by various other factors with important
      consequences for the development, prevention or treatment of amyloidosis. We have
      previously shown that laminin inhibits A beta peptide fibril formation in vitro.
      Here we present a kinetic study that indicates laminin to be a potent anti
      amyloidosis factor, as it not only inhibited A beta 1-40 fibril aggregation, but
      also inhibited the aggregation of the Dutch A beta 1-40 variant, a peptide with a
      higher capacity to aggregate than the wild-type A beta 1-40. The inhibitory
      effect of laminin on amyloid fibril formation was not overcome by the addition of
      pre-formed A beta fibrils, suggesting that laminin inhibits the fibril elongation
      process. At the present time, however, we cannot rule out the possibility that
      laminin also affects the initial nucleation process of A beta fibril formation.
      On other hand, laminin was not able to counteract the amyloid fibril formation
      promoted by acetylcholinesterase (AChE), another component of the amyloid
      deposits found in AD brains. The effect of laminin may be important as an
      inhibitor of A beta amyloidogenesis in vivo, specifically at the level of
      cerebral blood vessels.

PMID- 9547003
TI  - Transthyretin mutation (serine 84) associated with familial amyloid
      polyneuropathy in a Hungarian family.
AB  - A Hungarian family with familial amyloid polyneuropathy (FAP) was studied. The
      disease presented in two individuals with carpal tunnel syndrome in the fourth
      and fifth decades of life. The proband subsequently developed vitreous opacities
      requiring vitrectomy and now has evidence of cardiomyopathy. Single strand
      conformation polymorphism analysis and direct DNA sequencing revealed a variant
      AGC (serine) codon at amino acid position 84 of the amyloid precursor protein,
      transthyretin (TTR). The same single amino acid substitution in TTR was detected
      in an Indiana kindred with Swiss/German origin. Six individuals of the 11 tested
      being at risk for FAP proved to have the mutation in the present Hungarian
      kindred. This is the first description of this TTR gene mutation in Europe.
      Despite TTR gene haplotype analysis which suggests that the Hungarian and Indiana
      kindreds may have a common origin, no genealogical link has been identified
      between the families living in Indiana and Hungary.

PMID- 9547002
TI  - Synovial inflammatory cells captured 131I-beta 2-microglobulin in patients with
      dialysis related amyloidosis.
AB  - Dialysis related amyloidosis (DRA) is a major complication of long term
      hemodialysis therapy. It is well recognized that scintigraphic study using
      radioisotope-labeled beta 2-microglobulin (beta 2M) as a tracer is a sensitive
      and specific technique to diagnose DRA non-invasively. The aim of this study is
      to clarify the mechanism of 131I-beta 2M accumulation around the amyloid tissue.
      Three dialysis patients with carpal tunnel syndromes were examined for
      consecutive 131I-beta 2M scintigraphies every 24 hours for 3 days till the carpal
      tunnel synovectomy. Removed synovial tissues were processed for histological
      study. The scintigraphic study demonstrated tracer accumulations in the joints
      involved with DRA and the intensity increased in a time dependent fashion.
      Microscopic observations revealed many inflammatory cells presenting CD68
      monocytes/macrophages antigen infiltrated into the synovial tissues. 131I-beta 2M
      was evident in the cytoplasm of the infiltrating cells, while no radioactivity
      was detected above background in the amyloid tissues. In conclusion, the tracer
      accumulations observed in the 131I-beta 2M scintigraphic studies were the
      consequence of circulating beta 2M assimilated by the infiltrating
      monocytes/macrophages. Thus, the undetermined elimination pathway of circulating
      beta 2M in the dialysis patients was identified as the storage pool in those
      inflammatory cells. The inflammatory change may play a crucial role in the local
      progression of DRA through the accumulation of circulating beta 2M around the
      established amyloid tissues.

PMID- 9547004
TI  - Ultrastructural evidence for the formation of amyloid fibrils within
      cardiomyocytes in isolated atrial amyloid.
AB  - Isolated atrial amyloid (IAA) frequently affects elderly human hearts in which
      only the atria are involved by the deposits. Biochemical analysis has indicated
      that the major subunit protein of IAA is alpha-human atrial natriuretic peptide
      (alpha-ANP), which is synthesized by the atrial muscle cells. To define the exact
      location of the formation of IAA fibrils, right atria from 25 patients undergoing
      cardiac surgery have been examined by an immunohistochemistry and immunoelectron
      microscopy with anti-alpha-ANP, apolipoprotein E, amyloid P component,
      transthyretin, and cathepsin B antisera. Of 25 patients, 19 were involved with
      IAA deposits which reacted with anti-alpha-ANP, apolipoprotein E, amyloid P
      component antisera but not with anti-transthyretin antiserum. In 8 of them,
      amyloid fibrils were seen not only in the interstitium of the atrial myocardium
      but also in the dilated transverse tubules of the cardiomyocytes. In some
      cardiomyocytes, amyloid fibrils were also demonstrated within the organelles such
      as coated and uncoated secretory vesicles or lysosomes. These findings lead to
      the inescapable conclusion that the polymerization of amyloid fibrils in IAA
      occurs within the cytoplasm of cardiomyocytes under some conditions.

PMID- 9547005
TI  - An ultrastructural study of the colocalization of biglycan and decorin with AA
      amyloid fibrils in human renal glomeruli.
AB  - An investigation was undertaken on paraformaldehyde-fixed, Lowicryl resin
      embedded renal biopsies from patients with AA amyloidosis to study the
      association of two small chondroitin sulphate/dermatan sulphate proteoglycans,
      decorin and biglycan, with amyloid fibrils using an ultrastructural immunogold
      technique. Biglycan was present in glomerular endothelial cells in both normal
      kidney and in amyloidosis, but little biglycan or decorin was present in the
      normal mesangial matrix. By contrast, conspicuous amounts of both biglycan and
      decorin were seen to be associated with amyloid fibrils in the glomerular matrix
      in cases of renal AA amyloidosis. The results further emphasise the close
      association between amyloid and extracellular matrix components which are now
      considered to be an integral part of the amyloid fibrils.

PMID- 9547006
TI  - Local synthesis of amyloid fibril precursor in AL amyloidosis of the urinary
      tract.
AB  - An amyloid tumor localized to the urethra was resected and shown by
      immunohistochemistry to contain fibril deposits that stained with antisera
      specific for lambda VI immunoglobulin light chain. The amino acid sequence of the
      fibril protein was homologous to lambda VI Positive staining of subepithelial
      plasma cells with lambda VI specific monoclonal antibody was consistent with the
      hypothesis that the fibril precursor light chain protein is synthesized and
      processed locally to give this type of localized amyloidosis.

PMID- 9547007
TI  - Gelsolin-related familial amyloidosis, Finnish type (FAF), and its variants found
      worldwide.
AB  - Gelsolin-related familial amyloidosis, Finnish type, occurs worldwide, most
      likely as a result of sporadic low-frequency mutations. Two mutations at
      nucleotide 654 in the gelsolin gene have been demonstrated, which result in a
      characteristic triad of ophthalmologic, neurologic and dermatologic
      manifestations distinct from other amyloidoses. Some phenotypic variation,
      particularly in the age of onset and severity of manifestations, occurs but in
      general the disease is clinically rather homogeneous. Systemic deposition of
      amyloid is found in most tissues, predominantly in blood vessel walls and
      associated with basement membranes. The mutations result in amino acid
      substitutions with a charge change in the gelsolin molecule, postulated to alter
      the susceptibility for proteases thereby rendering the molecule amyloidogenic.
      Gelsolin fragments constitute the amyloid fibrils, but abnormal fragments also
      occur in patients' plasma and CSF providing evidence for the role of aberrant
      proteolysis in the disease pathomechanism. This is further strengthened by in
      vitro expression analyses showing both disease-related mutations to result in
      secretion of an abnormal gelsolin fragment, the likely precursor protein of
      gelsolin amyloid. Of the two forms of gelsolin, secretory and cytoplasmic, the
      secretory plasma form is the likely source of amyloid. The origin of the systemic
      amyloid deposits is not known but, beside a circulatory origin, local synthesis
      and deposition is an attractive pathomechanical alternative. The final goal of
      preventing or curing this disease has come closer, but still awaits further
      comprehensive pathological, functional and experimental studies in order to
      dissect all pathogenetically important events.

PMID- 9547008
TI  - Tenth and eleventh Amyloidforum at the 80th and 81st annual meeting of the German
      Society for Pathology, June 1, 1996 in Dresden and May 24, 1997 in Berlin,
      Germany.

PMID- 9547009
TI  - Localized genitourinary amyloidosis: a new form of light chain disease.

PMID- 9547011
TI  - Oxazole yellow dye interactions with short DNA oligomers of homogeneous base
      composition and their hybrids.
AB  - Interactions between short single-stranded DNA oligomers of homogeneous base
      composition and the fluorescent probes oxazole yellow (YO) and its homodimer YOYO
      are described. The oligomers included 15-mers and 30-mers of polydA, polydT,
      polydG, and polydC. Interactions between the dyes and DNA hybrids formed from
      complementary homogeneous strands of equal length were also investigated. No
      interactions were observed between the dyes and the monomeric monophosphate
      nucleosides A, G, T, or C. The dyes were found to interact much more strongly
      with the purine oligomers polydA and polydG than with the pyrimidine oligomers
      polydT and polydC. PolydA of both lengths has strong interactions with YOYO,
      whereas the polydG 30-mer interacts strongly with monomeric YO. The 15-mers of
      polydG and polydC of both lengths show little interaction with either dye.
      Interactions of the dyes with the polydA/polydT and polydG/polydC hybrids tend to
      be dominated by interactions with polydA and polydG, respectively. Although dye
      interactions generally were facilitated by hybridization, particularly for
      polydA/polydT, the interactions were similar to those with the single strands and
      different from those that have been observed in long double-stranded DNA.

PMID- 9547010
TI  - Cyanide binding and active site structure in heme-copper oxidases: normal
      coordinate analysis of iron-cyanide vibrations of a3(2+)CN- complexes of
      cytochromes ba3 and aa3.
AB  - The cyanide isotope-sensitive low-frequency vibrations of ferrous cyano complexes
      of cytochrome a3 are studied for cytochrome ba3 from Thermus thermophilus and
      cytochrome aa3 from bovine heart. Cyanide complexes of ba3 display three isotope
      sensitive frequencies at 512, 485, and 473 cm-1. The first is primarily an Fe-C
      stretching motion, whereas the lower wavenumber modes are bending motions. These
      iron-cyanide vibrations are independent of the redox levels of the other metal
      centers in the protein. On the other hand, the fully reduced bovine derivative
      complexed with cyanide gives rise to a bending vibration at 503 cm-1 and a
      stretching vibration at 469 cm-1. That is, the ordering of the stretching and
      bending frequencies is reversed from that of the bacterial protein. These results
      are analyzed by normal coordinate calculations to obtain comparative models for
      the binuclear O2 reducing site of the two proteins. We find that the observed
      frequencies are consistent with a linear Fe-C-N group and larger Fe-C stretching
      force constant (2.558 mdyn/A) for ba3 and a slightly bent Fe-C-N group (angle
      approximately 170 degrees) and a smaller Fe-C stretching force constant (2.335
      mdyn/A) for aa3. Thus, there are significant differences in the interaction of
      cyanide with ferrous a3 in the two proteins that are most likely caused by a
      weaker proximal histidine interaction and stronger peripheral heme electron
      withdrawing effects in ba3. Possible sources of these protein-induced effects are
      discussed. Using the analysis developed here, comparison of the FeCN stretching
      and bending frequencies of the ferrous bovine a3-CN complex to those obtained
      from the ferric a3-CN complex suggests that upon conversion of the resting to the
      fully reduced protein, a conformational change occurs that constrains the ligand
      binding site.

PMID- 9547012
TI  - Spectroscopic studies of single-stranded DNA ligands and oxazole yellow dyes.
AB  - Interactions between short single-stranded DNA ligands and fluorescent DNA
      indicator dyes were used to investigate binding selectivity of the ligands.
      Conformational differences among four DNA ligands of different sequence and
      structure, including two that form a G-quartet and two that do not, were
      confirmed by circular dichroism spectroscopy. Their interactions with indicator
      dyes YO-pro-1 iodide (YO) and YOYO-1 iodide (YOYO) were probed using measurements
      of dye absorbance; induced circular dichroism; and fluorescence spectra,
      anisotropy, and lifetime. Equilibrium binding constants and stoichiometry were
      determined as well. Results indicate significant differences among the dye
      interactions and binding stoichiometries of the four ligands. One of the G
      quartet forming ligands, a 20-mer of sequence 5'-GGTTTTGGTTTTGGTTTTGG-3', shows
      distinctly different interactions from the other three ligands, all of which are
      15-mers. These studies illustrate the importance of sequence and conformation in
      determining the binding interactions of short single-stranded DNA.

PMID- 9547013
TI  - Cancer grading by Fourier transform infrared spectroscopy.
AB  - Thirty-nine freeze-dried tissue samples from 17 lymphoid tumors (nine malignant
      non-Hodgkin's lymphomas) were studied by Fourier transform infrared (FTIR)
      spectroscopy. The absorbance ratio A1121/A1020 increased, along with the
      emergence of an absorbance pulse at 1121 cm-1, with increasing
      clinicopathological grade of malignant lymphoma. An increasing A1121/A1020 ratio
      from benign to malignant is evident in literature spectra from several different
      tissues; however, the present study is the first to comment on this effect and to
      propose it as an index of the cellular RNA/DNA ratio after subtraction of
      overlapping absorbances, if present, due to collagen or glycogen. Absorbance
      attributable to collagen increased with lymphoma grade and was greater in benign
      inflammatory tumors than in low-grade lymphomas. The A1121/A1020 trend observed
      here may form the basis of a universal cancer-grading parameter to assist with
      cancer treatment decisions and may also be useful in the analysis of cellular
      growth perturbation induced by drugs or other therapies. Our spectral findings
      may potentially be applied to cell clusters and discrete areas of tumor tissue
      sections using the FTIR microscope, allowing correlation with morphology and a
      high degree of spatial resolution.

PMID- 9547014
TI  - Infrared spectroscopy of human tissue. I. Differentiation and maturation of
      epithelial cells in the human cervix.
AB  - Infrared spectral results for the different epithelial layers of human cervical
      squamous tissue are reported. The layers, representing different cellular
      maturation stages, exhibit quite different spectral patterns. Thus, infrared
      spectroscopy presents a powerful tool to monitor cell maturation and
      differentiation. Furthermore, a detailed understanding of the spectra of the
      individual layers of tissue permit a proper interpretation of the state of health
      of cells exfoliated from such tissue. Part II of this series describes the use of
      the spectral information presented here to interpret the infrared spectra of
      exfoliated cells.

PMID- 9547015
TI  - Infrared spectroscopy of human tissue. II. A comparative study of spectra of
      biopsies of cervical squamous epithelium and of exfoliated cervical cells.
AB  - A comparison of infrared absorption spectra obtained from the different layers of
      squamous epithelium from the human cervix, and infrared spectra obtained from
      exfoliated cervical cells, is presented. Infrared spectroscopy has been shown (in
      part I of this series) to be a sensitive tool to monitor maturation and
      differentiation of human cervical cells; therefore, this spectroscopic technique
      provides new insights into the composition and state of health of exfoliated
      cells.

PMID- 9547016
TI  - Raman scattering tensors of tyrosine.
AB  - Polarized Raman scattering measurements have been made of a single crystal of L
      tyrosine by the use of a Raman microscope with the 488.0-nm exciting beam from an
      argon ion laser. The L-tyrosine crystal belongs to the space group P2(1)2(1)2(1)
      (orthorhombic), and Raman scattering intensities corresponding to the aa, bb, cc,
      ab and ac components of the crystal Raman tensor have been determined for each
      prominent Raman band. A similar set of measurements has been made of L-tyrosine
      d4, in which four hydrogen atoms on the benzene ring are replaced by deuterium
      atoms. The effects of NH3-->ND3 and OH-->OD on the Raman spectrum have also been
      examined. In addition, depolarization ratios of some bands of L-tyrosine in
      aqueous solutions of pH 13 and pH 1 were examined. For comparison with these
      experimental results, on the other hand, ab initio molecular orbital calculations
      have been made of the normal modes of vibration and their associated
      polarizability oscillations of the L-tyrosine molecule. On the basis of these
      experimental data and by referring to the results of the calculations,
      discussions have been presented on the Raman tensors associated to some Raman
      bands, including those at 829 cm-1 (benzene ring breathing), 642 cm-1 (benzene
      ring deformation), and 432 cm-1 (C alpha-C beta-C gamma bending).

PMID- 9547017
TI  - The diversity of volume regulatory mechanisms.
AB  - Mammalian cells utilize a wide variety of cell volume regulatory mechanisms. For
      rapid adjustment of cell volume cells release or accumulate ions through
      respective channels and transport systems across the cell membrane. The most
      widely used mechanisms of cell volume regulatory ion release include ion channels
      and KCl symport. Ion uptake is most frequently mediated by Na+ channels, Na+, K+,
      2Cl- cotransport, and Na+/H+ exchange. Chronic adjustment of cell osmolarity is
      accomplished by the formation or accumulation of organic osmolytes, molecules
      specifically designed to create intracellular osmolarity without interfering with
      cellular function. The most widely occurring osmolytes are sorbitol, inositol,
      glycerophosphorylcholine, betaine, taurine, and amino acids. The osmolytes are
      either synthesized by or transported into shrunken cells. During cell swelling
      osmolytes can be rapidly degraded or released. Any given cell may utilize several
      volume-regulatory mechanisms. Moreover, different mechanisms are utilized in
      different tissues. The diversity of cell volume regulatory mechanisms allows the
      cells to defend the constancy of cell volume against a myriad of challenges with
      relatively little impairment of cellular function.

PMID- 9547018
TI  - Endogenous angiotensin II and cell hypertrophy in vascular smooth muscle cultures
      from hypertensive Ren-2 transgenic rats.
AB  - We investigated the possible role of a tissular renin-angiotensin system in
      promoting the growth of vascular smooth muscle cells (VSMCs) from hypertensive
      transgenic rats (TGRs) with the mouse renin gene Ren-2. Mean arterial pressure
      values were 99.4 +/- 2.8 and 186.7 +/- 5.0 mm Hg for control Sprague-Dawley rats
      (SDs) and TGRs, respectively (p < 0.05). The tunica media of femoral arteries
      obtained from hypertensive TGRs was found to be thickened compared to that of age
      matched normotensive SDs. Angiotensin II could be detected by dot blot and
      immunocytochemistry and quantified by radioimmunoassay in transgenic VSMCs, but
      not in control SD ones. Under serum-free conditions, VSMCs derived from TGRs
      showed a higher protein content than those derived from SDs (337 +/- 19 vs. 269
      +/- 14 pg/cell, p < 0.05, n = 3). Under the same basal conditions, the mean
      planar cell surface area was significantly higher in TGR VSMCs than in SD ones
      (4,764 +/- 204 vs. 4,074 +/- 238 micron 2, p < 0.05). In addition, TGR VSMCs
      showed an enhanced [14C]-leucine uptake but SD VSMCs did not (13,188 +/- 663 vs.
      7,633 +/- 713 dpm/well, p < 0.05). VSMCs showed a concentration-dependent
      proliferative response to fetal calf serum (FCS) that was more marked in TGRs
      than in SDs. In the absence of FCS, c-fos and c-jun mRNAs were expressed only in
      transgenic cultures. From the present results, we can hypothesize that cultured
      TGR VSMCs are able to synthesize angiotensin II that, being almost exclusive into
      the cells, contributes to produce VSMC growth in the absence of FCS stimulation.

PMID- 9547019
TI  - Functional evidence for a pH sensor of erythrocyte K-Cl cotransport through
      inhibition by internal protons and diethylpyrocarbonate.
AB  - The sidedness of proton modulation of K-Cl cotransport (K-Cl COT) was studied in
      low K sheep red blood cells stripped of cellular Mg, Mgi, at alkaline medium pH,
      pHo, by the divalent ionophore A23187 and a chelator. This procedure activates K
      Cl COT, presumably, by inhibition of MgATP-dependent kinases. Ouabain-resistant K
      efflux and Rb influx were measured in Cl or NO3 either at variable pHi and fixed
      pHo, or vice versa, in erythrocytes pH- and volume-clamped with the anion
      exchange inhibitor 4,4'-diisothiocyanato-2,2'-disulfonic stilbene (DIDS) and
      sucrose. Between pHi 9 and 6, and at constant pHo 9, K effluxes decreased
      hyperbolically in Cl and linearly in NO3 whereas Rb influxes fell almost linearly
      in Cl and asymptotically in NO3. Thus, saturation of outward and inward K-Cl COT,
      the calculated difference of the fluxes in Cl and NO3, occurred at slightly
      different pHi values. Hill plots revealed pKa values of 6.5 and 7.0, and Hill
      coefficients of > 1 for outward and inward K-Cl COT, respectively. Raising pHo
      from 6 to 9 at fixed pHi slightly increased K and Rb fluxes in both Cl or NO3,
      but not K-Cl COT. The histidine reagent diethylpyrocarbonate (DEPC) inhibited low
      Mgi-activated K-Cl COT at approximately 4 mM, an effect partially reversible by
      subsequent treatment with hydroxylamine. It is concluded that protons inhibit
      erythrocyte K-Cl COT through internal histidine(s) which may be part of a pH
      sensor.

PMID- 9547020
TI  - Expression of cystic fibrosis transmembrane conductance regulator alters the
      responses to hypotonic cell swelling and ATP of Chinese hamster ovary cells.
AB  - The aim of this study was to examine whether the stable expression of wild-type
      cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese hamster
      ovary (CHO) cells alters the properties of these cells towards hypotonic cell
      swelling and ATP. According to many previous studies this was not expected a
      priori, since overexpression of CFTR should not affect the conductive pathways
      upregulated by the purinergic agonist or cell swelling. Three types of CHO cells
      were examined: a control group of normal CHO cells; a group of CFTR-CHO cells
      stably expressing wild-type CFTR at high levels (CHO-CFTR), and a group delta
      F508-CFTR-CHO cells, stably expressing the frequent mutation delta F508 CFTR (CHO
      delta F508). Whole cell patch-clamp studies were performed to measure the
      membrane voltage (Vm), the membrane conductance (Gm), and the membrane
      capacitance (C(m)). Hypotonic cell swelling (Hypo, 150 mosm/l) was used, because
      it activates Cl- and K+ channels and enables the cell to extrude KCl in many
      cells, and ATP because it is known to activate Ca(2+)-regulated channels in a
      large variety of cells. Hypo depolarized all three types of cells. This
      depolarization was accompanied by an increase in Cl- conductance. The selectivity
      of the conductance was I- > or = Br- > or = Cl- in CHO cells, but Cl- = Br- = I-
      in the CFTR cells. Even more surprising: ATP (100 mumol/l) hyperpolarized CHO and
      delta F508 cells and predominantly enhanced K+ conductance, whilst it depolarized
      and increased mostly a Cl- conductance in CFTR cells. The selectivity of this
      anion conductance was atypical for ATP: Br- > Cl- > I-. C(m) was increased by ATP
      and Hypo in all three types of cells. ATP enhanced cytosolic Ca2+ ([Ca2+]i) in
      all three types of cells but did not enhance cAMP. These data indicate that the
      expression of CFTR profoundly alters the properties of CHO cells. Agonists which
      stimulate characteristic Ca(2+)-regulated channels now enhance a Cl- conductance
      resembling the properties of CFTR-Cl- conductance.

PMID- 9547021
TI  - Influence of hypoxia and glucose deprivation on tumour necrosis factor-alpha and
      granulocyte-macrophage colony-stimulating factor expression in human cultured
      monocytes.
AB  - Ischaemia in wounds may modulate the expression of tumour necrosis factor-alpha
      (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The
      release of these and other cytokines by stimulated macrophages influences wound
      healing. Our aim was to examine the separate and combined effects of hypoxia and
      glucose deprivation on TNF-alpha and GM-CSF mRNA levels in human monocytes
      isolated from peripheral blood by density gradient centrifugation and purified by
      adherence. Cells were incubated for a 16-hour period in a hypoxic (3% O2) or
      normoxic (21% O2) environment in the presence or absence of glucose followed by a
      further 4 h under normoxic conditions in the presence or absence of
      lipopolysaccharide (LPS, 100 pg/ml). These different incubation conditions had no
      effect on cell viability, cell number, lactate dehydrogenase release or
      superoxide anion generation (n = 5, p > 0.05, paired t test). However, Northern
      hybridisation showed that hypoxia decreased the expression of GM-CSF mRNA in LPS
      stimulated human monocytes by 46% (n = 9, p < 0.05, paired t test) and increased
      the expression of TNF-alpha by 102% (n = 7, p < 0.05, paired t test). The
      increase in the level of immunoreactive TNF-alpha in the cell supernatants
      paralleled the increase in TNF-alpha mRNA. The combination of glucose deprivation
      and hypoxia decreased the expression of both GM-CSF and TNF-alpha mRNA in LPS
      stimulated human monocytes. Similarly, a decrease in the level of TNF-alpha in
      the cell supernatants was observed (n = 3-5, p < 0.05, two-way ANOVA). These data
      suggest that incubation conditions simulating ischaemia reduce LPS-induced
      cytokine expression.

PMID- 9547022
TI  - A Ba(2+)-insensitive K+ conductance in the basolateral membrane of rabbit
      cortical thick ascending limb cells.
AB  - The nature of the K+ exit across the basolateral membrane of microperfused rabbit
      cortical thick ascending limbs (cTALs) was investigated using the transepithelial
      and transmembrane potential difference (PDte, PDbl) and conductance measurements.
      An increase in bath K+ concentration from 4 to 10, 25, 50 mmol/l depolarized the
      basolateral membrane in a concentration-dependent manner, accompanied by a
      decrease in the fractional resistance of the basolateral membrane (FRbl). The Cl-
      channel blocker, 5-nitro-2-(3-phenylpropyl-amino)-benzoic acid (NPPB), did not
      prevent these effects. The effect of Ba2+ on PDbl was bimodally distributed:
      paradoxically, in the tubules in which Ba2+ largely depolarized, the effects on
      PDbl of the bath K+ concentration increases were not inhibited by extracellular
      Ba2+, in tubules in which Ba2+ moderately depolarized, Ba2+ partially inhibited
      the K+ concentration increase-induced depolarization of the basolateral membrane.
      However, the parallel decrease in FRbl was Ba2+ insensitive, indicating that the
      K+ channel of the basolateral membrane was not modified by extracellular Ba2+.
      The Ba(2+)-induced depolarizations were prevented by furosemide suggesting that
      Ba2+ acts by inhibiting basolateral KCl extrusion. Finally, the K+ concentration
      increase-induced depolarizations were insensitive to tetraethylammonium,
      charybdotoxin, apamin and verapamil. In conclusion, the present study provides
      evidence that, in addition to a Ba(2+)-sensitive KCl cotransport system, the
      basolateral membrane of rabbit cTAL cells possesses a K+ conductance which is
      insensitive to extracellular Ba2+.

PMID- 9547024
TI  - Pathophysiology of acute ischemic stroke: new concepts in cerebral embolism.

PMID- 9547023
TI  - Are more complex study designs needed for future acute stroke trials?

PMID- 9547025
TI  - Ancrod in the treatment of acute ischemic stroke. A review of clinical data.

PMID- 9547026
TI  - Controlling acute elevation of plasma fibrinogen with ancrod.

PMID- 9547027
TI  - The pharmacology of thrombolytic and fibrinogen-depleting agents in the treatment
      of acute ischaemic stroke.

PMID- 9547029
TI  - Is there a need to reclassify acute stroke patients?

PMID- 9547028
TI  - Acute stroke therapy in Europe today.

PMID- 9547030
TI  - Occupational stress and health care use.
AB  - This study investigated the relationship between health care use and (a)
      stressful work events; (b) strain; (c) social support; (d) type of job and
      industry; and (e) the individual characteristics of control, commitment, and
      length of time in position. A sample of 260 individuals (95 men, 165 women) from
      two different industries was used. Correlational analyses suggested that health
      care claims and costs were positively related to stressful work events and strain
      and negatively related to employees' length of time in position. Industry type
      also played a role in predicting the health care variables. Multivariate analyses
      suggested that environmental, stressor, and strain variables accounted for up to
      16% of the variance in health care costs and 21.5% of the variance in number of
      health care claims.

PMID- 9547031
TI  - Adverse health effects of high-effort/low-reward conditions.
AB  - In addition to the person-environment fit model (J. R. French, R. D. Caplan, & R.
      V. Harrison, 1982) and the demand-control model (R. A. Karasek & T. Theorell,
      1990), a third theoretical concept is proposed to assess adverse health effects
      of stressful experience at work: the effort-reward imbalance model. The focus of
      this model is on reciprocity of exchange in occupational life where high-cost/low
      gain conditions are considered particularly stressful. Variables measuring low
      reward in terms of low status control (e.g., lack of promotion prospects, job
      insecurity) in association with high extrinsic (e.g., work pressure) or intrinsic
      (personal coping pattern, e.g., high need for control) effort independently
      predict new cardiovascular events in a prospective study on blue-collar men.
      Furthermore, these variables partly explain prevalence of cardiovascular risk
      factors (hypertension, atherogenic lipids) in 2 independent studies. Studying
      adverse health effects of high-effort/low-reward conditions seems well justified,
      especially in view of recent developments of the labor market.

PMID- 9547032
TI  - Occupational health psychology (OHP) is moving forward from the crossroads of
      health psychology and public health.

PMID- 9547033
TI  - The influence of the work environment on cardiovascular health: a historical,
      conceptual, and methodological perspective.
AB  - The framework of psychosocial epidemiology is used to examine research
      developments that characterize the accumulation of knowledge regarding the role
      of the work environment in cardiovascular health and disease. The discussion of
      current programs of research focuses on the work of T. Theorell and R. Karasek
      (1996) and J. Siegrist (1996) as exemplars of European and American studies that
      have contributed the most to the understanding of occupational cardiovascular
      health. It is argued that researchers need to maintain and nurture relatively
      broad conceptual models of etiology because cardiovascular disease involves
      multiple biomedical risk factors and because specific aspects of the work
      environment are embedded in a large, complex matrix of other psychosocial
      influences. At the same time, investigators need to push ahead with focused
      research strategies to clarify the precise nature of the work environmental risk
      factors that emerge in the broad, somewhat imprecise epidemiologic study designs.

PMID- 9547034
TI  - Work-family conflict, gender, and health-related outcomes: a study of employed
      parents in two community samples.
AB  - On the basis of identity theory and research on sex role socialization, it was
      predicted that both work interfering with family (W-->F conflict) and family
      interfering with work (F-->W conflict) are uniquely related to depression, poor
      physical health, and heavy alcohol use (Hypothesis 1). It also was predicted that
      gender would moderate these relationships, such that W-->F conflict is more
      strongly related to the outcomes among women (Hypothesis 2a) and F-->W conflict
      is more strongly related to the outcomes among men (Hypothesis 2b). Survey data
      were obtained from 2 random community samples of employed parents (Ns = 496 and
      605). Hierarchical regression analyses supported Hypothesis 1 but failed to
      support Hypotheses 2a and 2b.

PMID- 9547035
TI  - Conceptual and methodological developments in occupational stress research: an
      introduction to state-of-the-art reviews. I.
AB  - This article introduces the first special section of state-of-the-art reviews.
      The historical origins of occupational health psychology are briefly discussed to
      establish a context for the present contributions that focus on job strain,
      effort-reward imbalance, and methodological problems.

PMID- 9547036
TI  - Organizational impact of workaholism: suggestions for researching the negative
      outcomes of excessive work.
AB  - Excessive work can be viewed as an addictive behavior, and, as such, it will have
      a negative impact on the setting in which it occurs, as well as on the
      individual. This change in perspective is needed to address dysfunctional
      behavior patterns that interfere with organizational operations. Similarities
      with other addictions include identity issues, rigid thinking, withdrawal,
      progressive involvement, and denial. These factors influence decision making and
      goals of the workaholic. They also interfere with effectiveness by distorting
      interpersonal relations. Suggestions for further research build on established
      organizational topics that coincide with characteristics of an addictive pattern.

PMID- 9547037
TI  - Behavioral determinants of occupational exposure to chemical agents.
AB  - In the demand-control model (see T. Theorell & R. A. Karasek, 1996), it is
      hypothesized that workers in active jobs (high demands-high decision latitude)
      can exert effective coping strategies when confronted with environmental
      stessors. Thus, when exposed to similar levels of a chemical agent, lower
      concentrations of this agent in blood could be expected in these workers in
      comparison with workers in passive jobs. This theory was tested in 2 studies of
      lead-exposed workers: 18 male Caucasian workers from an electric accumulatory
      factory and 18 male Caucasian workers from a lead smelting factory. The results
      did not follow the hypothesized outcomes. In the work environment of the workers
      in active jobs, lower concentrations of lead in air were measured, but higher
      levels of lead in blood were observed in these workers. The opposite was true of
      workers in passive jobs. Differences in hygienic behavior at work may explain
      these unexpected results.

PMID- 9547038
TI  - Current issues relating to psychosocial job strain and cardiovascular disease
      research.
AB  - The authors comment on recent reviews of cardiovascular job strain research by P.
      L. Schnall and P. A. Landsbergis (1994), and by T. S. Kristensen (1995), which
      conclude that job strain as defined by the demand-control model (the combination
      of contributions of low job decision latitudes and high psychological job
      demands) is confirmed as a risk factor for cardiovascular mortality in a large
      majority of studies. Lack of social support at work appears to further increase
      risk. Several still-unresolved research questions are examined in light of recent
      studies: (a) methodological issues related to use of occupational aggregate
      estimations and occupational career aggregate assessments, use of standard scales
      for job analysis and recall bias issues in self-reporting; (b) confounding
      factors and differential strengths of association by subgroups in job strain
      cardiovascular disease analyses with respect to social class, gender, and working
      hours; and (c) review of results of monitoring job strain-blood pressure
      associations and associated methodological issues.

PMID- 9547039
TI  - Employee drug use, demographic characteristics, work reactions, and absenteeism.
AB  - Employees in a large work organization participated in an investigation of
      relationships between drug use and absenteeism and tardiness. Specifically, the
      study investigated the extent to which both self-reported and urine-screened drug
      use accounted for variance in several types of absenteeism, as well as tardiness,
      above and beyond that accounted for by demographic and work reaction variables.
      The results showed that employee drug use accounted for additional statistically
      significant variance in overall absenteeism and in absenteeism due to injuries
      and suspensions, as well as days tardy. Implications of these findings for
      organizational drug testing are discussed.

PMID- 9547040
TI  - Extending the boundaries of occupational health psychology: state-of-the-art
      reviews. II.
AB  - The nature of work changes over the life course for both men and women, yet the
      substance and meaning of both paid and unpaid activities varies considerably by
      gender. The articles in this special section extend the study of work and health
      by applying an ecology of the life course perspective to retirement, by extending
      the definition of work to include unpaid activity outside formal employment, and
      by examining the elements of causal analysis in longitudinal studies.

PMID- 9547041
TI  - Influence of paid and unpaid work on psychophysiological stress responses of men
      and women.
AB  - Female labor force participation has increased considerably, but women's
      traditional responsibility for home and family has not changed accordingly.
      Although women's employment per se does not seem to have negative health
      consequences, studies show that stress from role conflicts and work overload is
      reflected in women's elevated psychophysiological arousal not only at work but
      also off work, which may induce psychosomatic symptoms (e.g., cardiovascular and
      musculoskeletal disorders). In addition, multiple role demands reduce women's
      possibilities to make a professional career on the same terms as men. Data
      emphasize the need for a new allocation of work functions between the sexes and
      the need for organizational changes leading to more influence and control over
      work to make it possible for both men and women to combine a qualified job with a
      meaningful family life.

PMID- 9547042
TI  - A life course perspective on retirement, gender, and well-being.
AB  - The existing research literature on the links between retirement and physical and
      psychological health is examined. This synthesis characterizes the complexity of
      the relationship between retirement and health; points out potential gender
      differences in the nature, experience, and implications of retirement; and
      develops a life course model of the pathways through occupational career and
      retirement leading to health. Such a life course model suggests a research agenda
      that can produce important insights on the dynamics and consequences of the
      retirement transition, including the mechanisms and conditions linking withdrawal
      from employment to changes in health and well-being.

PMID- 9547043
TI  - Longitudinal studies in organizational stress research: a review of the
      literature with reference to methodological issues.
AB  - Demonstrating causal relationships has been of particular importance in
      organizational stress research. Longitudinal studies are typically suggested to
      overcome problems of reversed causation and third variables (e.g., social
      desirability and negative affectivity). This article reviews the empirical
      longitudinal literature and discusses designs and statistical methods used in
      these studies. Forty-three longitudinal field reports on organizational stress
      were identified. Most of the investigations used a 2-wave panel design and a
      hierarchical multiple regression approach. Six studies with 3 and more waves were
      found. About 50% of the studies analyzed potential strain-stressor (reversed
      causation) relationships. In about 33% of the studies there was some evidence of
      reverse causation. The power of longitudinal studies to rule out third variable
      explanations was not realized in many studies. Procedures of how to analyze
      longitudinal data are suggested.

PMID- 9547044
TI  - The effect of stress inoculation training on anxiety and performance.
AB  - Stress inoculation training is an intervention that has shown considerable
      promise; however, many questions arise regarding the application of this
      clinically based approach to more applied workplace settings. A meta-analysis was
      conducted to determine the overall effectiveness of stress inoculation training
      and to identify conditions that may moderate the effectiveness of this approach.
      The analysis was based on a total of 37 studies with 70 separate hypothesis
      tests, representing the behavior of 1,837 participants. Results indicated that
      stress inoculation training was an effective means for reducing performance
      anxiety, reducing state anxiety, and enhancing performance under stress.
      Furthermore, the examination of moderators such as the experience of the trainer,
      the type of setting in which training was implemented, and the type of trainee
      population revealed no significant limitations on the application of stress
      inoculation training to applied training environments.

PMID- 9547045
TI  - Self-esteem and the occupational stress process: testing two alternative models
      in a sample of blue-collar workers.
AB  - Blue-collar workers (4,523 men and 927 women) participated in a survey comparing
      two alternative models, one assuming the level of self-esteem (SE) to result to a
      significant extent from the strain induced by occupational stressors and the
      other stating the level of SE as a determinant of stressor perception and
      experienced strain. The results of multiple regression analyses did not support
      the latter model, whereas the first model was partially supported: Monotony was
      associated with increased strain and decreased SE among younger (< or = 35 years)
      male participants and older (> 35 years) female participants, and lack of control
      related to increased strain and decreased SE among older male participants. These
      observations were made in the context of psychological strain symptoms but not in
      the context of physiological strain symptoms.

PMID- 9547047
TI  - Dual-earner families: the importance of work stress and family stress for
      psychological well-being.
AB  - Scales of work stress and family stress as well as outcome measures of depression
      and self-esteem were completed by 94 mothers and 48 fathers in dual-earner
      families. Working mothers and working fathers reported equivalent levels of
      family stress, work stress, job-family interference, and psychological well
      being, although mothers did report a higher level of lack of task sharing. Self
      esteem and depression of dual-earner mothers and fathers were affected by both
      job and family stress. Insignificance within their work role affected both self
      esteem and depression. Lack of task sharing significantly predicted depression
      among dual-earner mothers. Lack of challenge in their work role appeared to be a
      positive characteristic for dual-earner fathers.

PMID- 9547046
TI  - Correlates and consequences of workplace violence.
AB  - A random telephone survey was used to interview 598 employees about instances, if
      any, when they had been physically attacked or threatened in the workplace.
      Demographic and workplace characteristics are analyzed as correlates of these
      forms of violence. The only characteristic consistently associated with higher
      risk is a work schedule that included nighttime hours. However, although few
      strong or consistent correlates of workplace violence were found, there were
      clear negative consequences associated with being victimized at work: lower job
      satisfaction, greater job stress, increased considerations of job change, and an
      increased likelihood of bringing mace, a gun, or another weapon to work.

PMID- 9547048
TI  - Gender and ethnic differences in social constraints among a sample of New York
      City police officers.
AB  - Gender and ethnic differences in social constraints on and off the job among a
      sample of 372 police officers was examined. Positive and negative social
      interactions with supervisors and coworkers, and perceptions of the work
      environment as well as support and resentment of the job from family and
      significant others, was included. As hypothesized, women and minority men
      reported more negative social interactions on the job, such as criticism, bias,
      and sexual harassment. Few differences were observed for positive social
      interactions on or off the job, and where differences emerged, women and minority
      men reported more favorable social interactions. These findings are discussed in
      terms of implications for intervention, policy, and future research.

PMID- 9547049
TI  - Contributing concepts and methods across disciplinary boundaries: state-of-the
      art reviews. III.
AB  - This article introduces the third special section of state-of-the-art reviews.
      The conceptual and methodologic contributions of the 3 articles in this section
      are framed, noting the importance of the public health, preventive medicine, and
      sociological disciplines represented.

PMID- 9547050
TI  - Job stress and cardiovascular disease: a theoretic critical review.
AB  - During the last 15 years, the research on job stress and cardiovascular diseases
      has been dominated by the job strain model developed by R. Karasek (1979) and
      colleagues (R. Karasek & T. Theorell, 1990). In this article the results of this
      research are briefly summarized, and the theoretical and methodological basis is
      discussed and criticized. A sociological interpretation of the model emphasizing
      theories of technological change, qualifications of the workers, and the
      organization of work is proposed. Furthermore, improvements with regard to
      measuring the job strain dimensions and to sampling the study base are suggested.
      Substantial improvements of the job strain research could be achieved if the
      principle of triangulation were used in the measurements of stressors, stress,
      and sickness and if occupation-based samples were used instead of large
      representative samples.

PMID- 9547051
TI  - Occupational stress, safety, and health: conceptual framework and principles for
      effective prevention interventions.
AB  - The authors present an overarching conceptual model of occupational stress,
      safety, and health, incorporating multiple factors from diverse disciplines. They
      examine specific implications of the model for the development of prevention
      interventions (e.g., context-specific interventions and primary, secondary, and
      tertiary prevention). They review prevention interventions and describe and
      analyze 4 case studies that address exposure to environmental, ergonomic, and
      psychosocial stressors and a combination of physical-environmental and
      psychosocial stressors. The authors examine lessons learned from these
      interventions in light of the conceptual model (e.g., role of top management and
      integrating research and intervention).

PMID- 9547052
TI  - Work-related stress and blood pressure: current theoretical models and
      considerations from a behavioral medicine perspective.
AB  - There is extensive evidence that the prevalence of human hypertension is related
      to psychosocial factors, possibly including chronic exposure to stress. A
      tripartite model, consistent with the literature on stress and health, may help
      to define this relationship better. Its 3 components are environmental stressors,
      individual factors affecting the perception of stress, and the individual's
      physiological susceptibility. To date, researchers have looked at individual
      parts of this model, but rarely at all 3. Some models of work stress (e.g., the
      job strain, effort-reward, and person-environment fit models) focus on work
      related stressors alone or in conjunction with individual characteristics. Other
      models (e.g., the defense-defeat, John Henryism, and reactivity models) focus on
      individual differences in response, with little attention paid to the nature of
      the stressors. The authors suggest that it is timely to integrate these
      approaches and to look for physiological mechanisms.

PMID- 9547053
TI  - Eldercare responsibilities, interrole conflict, and employee absence: a daily
      study.
AB  - A model was developed specifying that the number of hours employees spend
      providing care to or interacting with elderly parents predicts conflict between
      the roles of employee and caregiver. Interrole conflict was subsequently expected
      to predict partial absence from work (e.g., arriving late). Seventeen employed
      eldercare providers completed a daily questionnaire for 20 work days. The data
      were standardized and pooled, and the proposed model was tested by using
      structural equation modeling. The proposed model provided a good fit to the data.
      A competing model that added the direct effects of hours of interacting with and
      hours of providing care to parents on partial absence provided a significantly
      better fit. The potential impact of the findings on employees and organizations
      is discussed.

PMID- 9547054
TI  - Perceived race-based discrimination, employment status, and job stress in a
      national sample of black women: implications for health outcomes.
AB  - Previous research has not systematically examined the relationship of perceived
      race-based discriminations to labor force participation or job related stresses
      problems experienced by Black women. The present study investigated the relative
      contributions of perceived race-based discriminations and sociodemographic
      characteristics to employment status and job stress in a national probability
      sample (the National Survey of Black Americans; J. S. Jackson, 1991) of Black
      women in the United States. Logit and polychotomous logistic regression analyses
      revealed that Black women's current employment status was best explained by
      sociodemographic measures. In contrast, the combination of perceived
      discrimination and sociodemographics differentially affects patterns of
      employment status and perceived job stress in the work environment of Black
      women. Implications of these findings for the health of African American women
      are discussed.

PMID- 9547055
TI  - Construct validity of a Physical Work Environment Satisfaction Questionnaire.
AB  - Many theories of behavior at work fail to consider the effects of the physical
      environment on employees' behavior and attitudes. The purpose of this research
      was to gather evidence of the construct validity of the Physical Work Environment
      Satisfaction Questionnaire (PWESQ) and of the validity of the physical work
      environment satisfaction construct. Evidence of the construct validity of the
      PWESQ was sought through its administration, along with a number of established
      measures of work attitudes, to 641 employees in 8 organizations. The data
      provided evidence of the validity of both the physical work environment
      satisfaction construct and the PWESQ as a valid measure of that construct.
      Practical and theoretical implications, as well as implications for future
      research, are discussed.

PMID- 9547056
TI  - Advancing public policy, social science, and biomedical inquiry: state-of-the-art
      reviews. IV.
AB  - In this article, the author introduces the fourth special section of state-of-the
      art reviews. He discusses the public policy and epistemological contributions of
      the 2 articles in this section in terms of the translation of scientific research
      findings into public policy actions.

PMID- 9547057
TI  - Public policy and occupational health psychology in Europe.
AB  - Increasing evidence exists that workplace absence due to stress-related
      conditions is a growing problem in Europe. However, the priority on the issue
      varies between countries. The costs of occupational stress are difficult to
      accurately quantify, and the incentives for investing in stress-prevention
      activities are less apparent at an organizational level than in the United
      States. Consequently, expansion in this area has been considerably slower. The
      authors present an overview of the problems of occupational stress within Europe.
      They discuss the response and intervention characteristics of European employers
      and policymakers and possible developments. If organizations are to become more
      proactive in their approach to stress prevention, there needs to be a framework
      for assessing, implementing, and evaluating interventions. The authors outline a
      framework to adopt.

PMID- 9547058
TI  - Dialectic between conceptual and causal inquiry in psychosocial work-environment
      research.
AB  - In this article, the authors discuss the ongoing tension between etiologically
      oriented research--particularly that focused on the demand-control model--and the
      need to conceptually expand the work stress field to include gender and class
      specific exposure contexts. Epidemiological research on the effects of low levels
      of work control is critically reviewed, and new methods of long-term psychosocial
      work-exposure assessment are presented. The process of conceptually expanding the
      demand-control model is discussed with respect to including other important
      variables, such as work-related social support, and specifying the nature of the
      gendered work process that involves developing new concepts and measures of the
      invisible and emotional labor often performed by women.

PMID- 9547059
TI  - Hostility and hearing protection behavior: the mediating role of personal beliefs
      and low frustration tolerance.
AB  - The authors examined whether hostility would negatively be associated with
      occupational health behavior, namely, the use of hearing protection devices
      (HPDs). Also examined as possible mediators were the protection motivation theory
      (PMT) components and low frustration tolerance (LFT). Participants were 226 male
      industrial workers, all exposed to potentially hearing-damaging noise. Hostility
      was negatively related to HPD use. It moderately correlated with the PMT
      components: negatively with perceived susceptibility, severity, effectiveness,
      and self-efficacy and positively with perceived barriers. Hostility correlated
      highly with LFT. Regression analyses confirmed the mediating role of perceived
      barriers, low self-efficacy, and LFT in the negative relationship between
      hostility and the use of HPDs. Thus, intrapsychic characteristics of hostile
      people may be significant for hearing protection behavior.

PMID- 9547060
TI  - Leadership behavior and subordinate stress: a 360 degrees view.
AB  - Relationships between leader behavior and subordinate work stress were examined
      from the perspectives of 343 leaders, their bosses, and their subordinates.
      Leader behaviors did relate to stress experienced by staff; however, leaders'
      views of what related to subordinate stress did not always coincide with the
      factors that subordinates themselves associated with stress. The relationships of
      leader delegation and subordinate participation to lower subordinate reports of
      stress were particularly underestimated by leaders. Implications for developing
      leaders as agents for employee stress reduction are discussed.

PMID- 9547062
TI  - Relation of negative affectivity to self-reports of job stressors and
      psychological outcomes.
AB  - A total of 250 new women teachers participated in a longitudinal study of the
      influence of negative affectivity (NA) on the relation of self-report work
      environment measures to psychological outcomes. Three "neutrally worded" work
      environment measures were specially constructed to minimize confounding with NA.
      The work-environment measures were moderately related to postemployment
      depressive symptoms, job satisfaction, and, among Whites but not among a
      principally Black and Hispanic subsample, motivation. Correlation and regression
      coefficients were largely unchanged when the preemployment psychophysiologic
      symptoms scale and the Center for Epidemiologic Studies-Depression Scale (L. S.
      Radloff, 1977), factors that tap NA, were controlled. Findings suggest NA does
      not overly distort the relation of some self-report work-environment measures to
      depressive symptoms, satisfaction, and motivation.

PMID- 9547061
TI  - Work-related stress and psychological distress in emergency medical technicians.
AB  - Emergency medical technicians (N = 65) participated in a study on work
      environment characteristics, work-related stress, and psychological distress.
      Data were collected at baseline and 6 months. Work-related stress was associated
      with lower work group support and poor supervisory behavior. Work-related stress
      was strongly related to psychological distress. Changes in work-related stress
      were significantly related to changes in psychological distress. Findings support
      the work-related stress, psychological distress model.

PMID- 9547063
TI  - C band variation in polytene chromosomes of Chironomus riparius (Diptera,
      Chironomidae) from a polluted Piedmont station (Italy).
AB  - C banding in polytene chromosomes of Chironomus riparius from a Santena polluted
      station of the river Po, Italy was described. A large variation in the appearance
      of C bands was established. The process involved the transformation of
      euchromatin into heterochromatin. Activation of all chromosomes at telomeres was
      found. A structural modification of telomeric heterochromatin may exist. The
      centromeric heterochromatin was rarely observed. A high percentage of an
      amplification (88%) in arm F, B3h, was recorded. These changes in the appearance
      of heterochromatin in the population studied could be considered as a type of
      polymorphic system, existing in the polluted population. For the first time in C.
      riparius two types of position effect variegation are reported. In arm E the
      euchromatin near to the centromere became inactive due to a heterozygous
      inversion and in arms D and F the opposite phenomenon was observed in which a
      heterozygous inversion partly suppressed the inactivation of heterochromatin.

PMID- 9547064
TI  - Effect of Peganum harmala extract on root tips of Allium cepa.
AB  - Treatment with Peganum harmala extract remarkably increased the mitotic index in
      Allium cepa root tips with increasing treatment duration at all exposure times
      used and with almost all concentrations. The extract caused a relatively high
      increase in the mitotic index after a long period of treatment with some low
      concentrations.

PMID- 9547065
TI  - Causes and consequences of intrauterine growth retardation. Proceedings of an
      IDECG Workshop. Baton Rouge, Louisiana, USA. November 11-15, 1996.

PMID- 9547066
TI  - Changes in synaptology of adult cat spinal alpha-motoneurons after axotomy.
AB  - The aim of this electron-microscopic study was to analyze the distribution of
      synaptic contacts on the cell bodies and dendrites of permanently axotomized
      adult cat spinal alpha-motoneurons. Following transection and ligation of the
      medial gastrocnemius nerve, the synaptic covering of the cell bodies and three
      different dendritic compartments of homonymous alpha-motoneurons was analyzed
      quantitatively at 3, 6, and 12 weeks postoperatively. The synaptic boutons were
      classified according to their size and the shape of their synaptic vesicles. On
      the soma, a transient increase in the number of boutons was noted at 3 weeks and
      6 weeks postoperatively, while after 12 weeks the bouton number had decreased to
      half of its normal value. The transient increase was mainly due to an increase in
      the number of F-type boutons. At 12 weeks postoperatively, the synaptic covering
      was reduced by 83% on the soma and by 57% on the proximal dendrites. In the
      distal dendritic regions, the values for synaptic covering remained largely
      unchanged. In summary, axotomized motoneurons exhibit a reduction in synaptic
      covering which is maximal on the cell body and becomes less pronounced
      centrifugally along the dendrites. However, if also taking into account the loss
      of distal dendritic branches that occurs in axotomized motoneurons, the total
      loss of boutons is several times larger in the dendrites than on the soma.

PMID- 9547067
TI  - Movements modulate the reflex responses of human flexor pollicis longus to
      stretch.
AB  - The reflex responses to brisk, ramp stretch perturbations of the human flexor
      pollicis longus muscle (FPL) were recorded during isometric and slow concentric
      or eccentric contractions at similar levels of muscle excitation. The subjects
      flexed their thumb to push down against a thumb-rest, whose position was
      controlled by a servo-controlled motor. In different runs, the stretch
      perturbations were imposed when the thumb-rest was stationary (isometric) or was
      flexing or extending the interphalangeal joint of the thumb at a constant
      velocity, i.e. during concentric or eccentric contractions of FPL. The latency of
      the most prominent component of the electromyographic reflex in the isometrically
      contracting muscle was about 60 ms, measured from the command signal. The
      amplitude of this response was sharply reduced during the non-isometric
      contractions. While not dependent on the direction, this modulation of the reflex
      response increased with the speed of active movement of the interphalangeal joint
      (flexion or extension). The response was greatly reduced during concentric or
      eccentric movements as slow as 1.6 mm x s[-1] (approximately 5 degrees x s (-1)
      at the joint). When the force rather than the position of the thumb-rest was
      servo-controlled, the stretch response to perturbation again diminished with
      speed in a self-paced flexion task, compared with an isometric "hold" condition.

PMID- 9547068
TI  - Depletion of calcitonin gene-related peptide from the caudal trigeminal nucleus
      of the rat after electrical stimulation of the Gasserian ganglion.
AB  - Electrical stimulation of the Gasserian ganglion resulted in partial depletion of
      calcitonin gene-related peptide (CGRP) from ipsilateral central terminals of
      pseudounipolar primary sensory ganglion cells. Affected terminals exhibit
      decreased CGRP immunoreactivity as shown by cytophotometric densitometry of the
      caudal trigeminal nucleus. The decrease in CGRP immunoreactivity is statistically
      significant only in the medial one-third of the caudal trigeminal nucleus. Since
      earlier studies have shown that electrical stimulation of the Gasserian ganglion
      induces first accumulation then depletion of CGRP from perivascular sensory
      terminals in the dura mater, the present experiments suggest that CGRP is
      depleted also from central terminals of primary sensory trigeminal neurons, which
      might be of importance in the pathogenesis of migraine headache.

PMID- 9547069
TI  - Canal-otolith interactions in the squirrel monkey vestibulo-ocular reflex and the
      influence of fixation distance.
AB  - Natural head movements include angular and linear components of motion. Two
      classes of vestibulo-ocular reflex (VOR), mediated by the semicircular canals and
      otoliths (the angular and linear VOR, or AVOR and LVOR, respectively), compensate
      for head movements and help maintain binocular fixation on targets in space. In
      this study, AVOR/LVOR interactions were quantified during complex head motion
      over a broad range of fixation distances at a fixed stimulus frequency of 4.0 Hz.
      Binocular eye movements were recorded (search-coil technique) in squirrel monkeys
      while fixation distance (assessed by vergence) was varied using brief
      presentations of earth-fixed targets at various distances. Stimuli consisted of
      rotations around an earth-vertical axis and therefore always activated the AVOR.
      Horizontal and vertical AVORs were assessed when the head was centered over the
      axis of rotation and oriented upright (UP) and right-side-down (RD),
      respectively. AVOR gains increased slightly with increasing vergence in darkness,
      as expected given the small anterior position of the eyes in the head. Combined
      AVOR/LVOR responses were recorded when subjects were displaced eccentrically from
      the rotation axis. Eccentric rotations activated the AVOR just as when the head
      was centered, but added a translational stimulus which generated an LVOR
      component in response to interaural (IA) or dorsoventral (DV) tangential
      accelerations, depending on whether the head was UP or RD, respectively. When the
      head was eccentric and facing nose-out, the AVOR and LVOR produced ocular
      responses in the same plane and direction (coplanar and synergistic), and
      response magnitudes increased with increasing vergence. With the head facing nose
      in, AVOR and LVOR response components were oppositely directed (coplanar and
      antagonistic). The AVOR dominated the response when fixation distance was far,
      and phase was compensatory for head rotation. As fixation distance decreased
      toward the rotation axis, responses declined to near zero, and when fixation
      distance approached even closer, the LVOR component dominated and response phase
      inverted. The same pattern was observed for both horizontal (head UP) and
      vertical (head RD) responses. The LVOR was recorded directly by rotating subjects
      eccentrically but in the nose-up (NU) orientation. The AVOR then generated
      torsional responses to head roll, coexistent with either horizontal or vertical
      LVOR responses to tangential acceleration when the subject was oriented head-out
      or right-side-out, respectively. Only the LVOR response components were modulated
      by vergence. A vectorial analysis of AVOR, LVOR, and combined responses supports
      the conclusion that AVOR and LVOR response components combine linearly during
      complex head motion.

PMID- 9547070
TI  - Adaptational effects during human split-belt walking: influence of afferent
      input.
AB  - The modification of the normal locomotor pattern of humans was investigated using
      a split-belt locomotion protocol (treadmill belt speeds of 4.5 km/h and 1.5 km/h
      for the right and left legs, respectively) and also by changing afferent input
      from the legs (30% reduction or increase in body weight by suspending subjects in
      a parachute harness or by wearing a lead-filled vest). After a control-speed
      training period (10 min) of symmetrical walking (3 km/h each leg) and a period
      (10 min) of split-belt walking, the adjustment back to the control speed resulted
      in a mean speed difference between the right leg and the left leg of 0.85 km/h.
      Adjustment of belt speed on either side was performed by the hands using a
      potentiometer. For comparison, also speed adjustment by the feet via feedback
      derived from changes in the treadmill drive current was studied. No significant
      difference was obtained when both modes of adjustment were compared. Body
      unloading or loading during the training period resulted in an improved
      adjustment of treadmill belt speed. This suggests that load receptor information
      plays a major role in the programming of a new walking pattern.

PMID- 9547071
TI  - Perceptual learning in tactile hyperacuity: complete intermanual transfer but
      limited retention.
AB  - We investigated intermanual transfer and long-term retention of practice-related
      perceptual learning in the domain of tactile hyperacuity. Subjects discriminated
      a row of three dots in which the central dot was offset laterally from a row
      without such offset. Performance at the right index fingerpad improved with
      practice. Practice effects transferred essentially completely to the left index
      fingerpad. When tested some months later at the right index fingerpad, long-term
      retention of learning was limited and further practice was required to stabilize
      discrimination thresholds. Intermanual transfer of tactile learning appears to be
      a general phenomenon, while long-term retention appears to be limited in
      hyperacuity tasks.

PMID- 9547073
TI  - Differential activation of spinal dorsal horn units by subcutaneous formalin
      injection in the cat: an electrophysiological study.
AB  - In our previous report we found that subcutaneous (s.c.) formalin injection into
      the cutaneous receptive field (RF) of dorsal horn wide-dynamic-range (WDR) units
      and nociceptive primary afferent units resulted in a tonic, long-lasting increase
      in firing. However, s.c. formalin injection only resulted in a short-lasting
      increase in firing of non-nociceptive primary afferent units. In the present
      study, by using extracellular single-unit recording techniques we further studied
      effects of s.c. formalin on response properties of identified superficial-layer
      nociceptive-specific (NS) units and deeper-layer, low-threshold mechanoreceptive
      (LTM) units of L7 dorsal horn in urethane-chloralose-anesthetized cats. s.c.
      formalin injection into the RF of NS units resulted in a tonic, long-lasting
      increase in firing (7.08+/-0.42 spikes/s, n = 5), for more than 1 h, compared
      with the spontaneous background (1.42+/-0.03 spikes/s, n = 5). Formalin injection
      into the RF of LTM units also resulted in an increase in firing; however, the
      duration was short-lasting, for 25-520 s (152.92+/-46.73 s, n = 12). The present
      study demonstrated that s.c. injection of dilute formalin solution resulted in
      activation of not only nociceptive but also non-nociceptive dorsal horn units,
      suggesting that tissue injury caused by s.c. formalin results in vigorous injury
      discharges of peripheral nerve terminals, which subsequently leads to activation
      of primary afferent neurons and secondary dorsal horn neurons.

PMID- 9547072
TI  - Visual fixation offsets affect both the initiation and the kinematic features of
      saccades.
AB  - It is well known that the removal of a fixation point prior to the presentation
      of a peripheral target dramatically reduces saccadic reaction time (SRT). This
      effect has become known as the "gap effect". The present study examined several
      detailed kinematic variables to determine whether the removal of the fixation
      point also affects the manner in which saccades are produced. The findings
      indicate that saccades that were initiated after the removal of the fixation
      point had higher average velocities and reached greater peak velocities,
      accelerations, and decelerations than did saccades produced in the presence of
      the fixation point. The results suggest that the removal of the fixation point
      may affect the force-time curves of saccades in addition to affecting the time
      needed to initiate the saccades.

PMID- 9547074
TI  - Transient visual field defects induced by transcranial magnetic stimulation over
      human occipital pole.
AB  - Transient visual field defects (VFDs) and phosphenes were induced in normal
      volunteers by means of transcranial magnetic stimulation (TMS) using a circular
      magnetic coil of 12.5 cm diameter placed with its lower rim 2-4 cm above the
      inion in the midline. Subjects had to detect small, bright dots presented
      randomly for 14 ms in one of 60 locations on a computer screen resulting in a
      plot of the central 9 degrees of the visual field. In 8 of 17 subjects, transient
      VFDs were inducible at peak magnetic field strenghts of 1.1-1.4 T. In the central
      1-3 degrees, detection of targets was impaired in both the upper and lower visual
      field, whereas at 4-9 degrees large parts of only the lower visual field were
      affected with a sharp cut-off along the horizontal meridian. Targets at 1 degree
      in the lower field were affected with lower TMS intensities than corresponding
      locations in the upper or peripheral locations in the lower field. Detection of
      central targets was affected at more caudal stimulation sites than detection of
      peripheral targets. Phosphenes were elicitable in 14 of 17 subjects at clearly
      lower field strengths of 0.6-1.0 T. Many subjects perceived chromatophosphenes.
      From a discussion of the literature on patients with VFDs and the known
      topography of the human visual system, it is concluded that the transient VFDs at
      1-3 degrees are probably due to stimulation of both striate cortex (V1) and
      extrastriate areas (V2/V3), while VFDs in the lower visual field at
      eccentricities 4-9 degrees are due to stimulation of V2/V3 but not V1.

PMID- 9547075
TI  - Event-related potentials associated with correct and incorrect responses in a
      cued antisaccade task.
AB  - In an antisaccade task, subjects are instructed to inhibit a reflexive saccade
      towards a peripheral stimulus flash and to generate a saccade in the opposite
      direction. It has been shown recently that normal subjects will generate a high
      number of incorrect prosaccades in an antisaccade task if the fixation point is
      extinguished 200 ms before the stimulus appears and if a valid cue for the
      subsequent antisaccade is given during this gap period. In the present study we
      recorded cerebral event-related potentials from 19 scalp electrodes from normal
      subjects prior to correct and incorrect responses in a cued antisaccade task to
      investigate the neural processes associated with correct antisaccades and
      incorrect prosaccades in this task. Correct antisaccades and incorrect
      prosaccades were associated with a negative potential with a maximal amplitude
      around stimulus onset over the dorsomedial frontal cortex. This potential was
      higher prior to correct antisaccades than prior to incorrect prosaccades. The
      execution of a correct antisaccade was preceded by a shift of a negative
      potential from the parietal hemisphere contralateral to the visual stimulus
      towards the parietal hemisphere ipsilateral to the stimulus. These results
      support the view that the supplementary eye fields participate in the inhibition
      of incorrect saccades in a cued antisaccade task and show that the parietal
      cortex participates in generating a neural representation of the visual stimulus
      in the hemifield ipsilateral to the stimulus before generating a motor response.

PMID- 9547077
TI  - Pain and Stroop interference tasks activate separate processing modules in
      anterior cingulate cortex.
AB  - Investigations of pain using functional imaging techniques have revealed an
      extensive central network associated with nociception. This network includes the
      thalamus, insula, prefrontal cortex and anterior cingulate cortex (ACC) as well
      as the somatosensory cortices. Positron emission tomography (PET) of regional
      cerebral blood flow (rCBF) has demonstrated activation of the ACC during
      cognitively challenging tasks such as the Stroop interference task and divided
      attention. One interpretation of this research is that ACC is involved in the
      general features of attention and that it does not play a specific role in pain
      processing per se. Three-dimensional PET imaging provides a method for
      assessments of rCBF in a single individual during multiple tasks. In addition,
      coregistration of PET and magnetic resonance (MR) images allows for better
      localisation of the PET signals so that differences in cortical activation sites
      can be more accurately determined. This approach was used to assess rCBF during
      the experience of pain by subtracting images collected during heat from those
      during noxious heat stimulation. Two regions of the ACC had elevated rCBF, one in
      the perigenual region and one in the mid-rostrocaudal region (i.e. midcingulate
      cortex). During the execution of the Stroop task, the group result showed the
      midcingulate region overlapping with the site seen during the experience of pain.
      This group result, however, was not confirmed in the individual subject analysis,
      which revealed widespread and independent areas of ACC response to pain and
      Stroop. It is concluded that the ACC contributes to multiple cognitive
      procedures. It is inadequate to describe the primary contribution of ACC to pain
      processing as "attention" because it is unlikely that the multiple small and
      independent activation sites produced by pain and Stroop subserve attentive
      processing throughout the brain.

PMID- 9547076
TI  - Common principles underlying the control of rapid, single degree-of-freedom
      movements at different joints.
AB  - Studies of rapid, single degree-of-freedom movements have shown different changes
      in electromyographic patterns for movement tasks that appear very similar (e.g.,
      movements over different ranges of distance). However, it is not clear whether
      these differences are a result of joint-specific control schemes or whether they
      are instead due to the limited range of task parameters studied relative to the
      mechanical constraints of each joint (e.g., short compared with long movements
      relative to the range of motion of a particular joint). In this study, we
      measured and compared the kinematic trajectories and electromyograms recorded
      during various movement tasks at the wrist, elbow, and ankle. Subjects performed
      movements over a wide range of distances "as fast as possible," "at a comfortable
      speed," and against two inertial loads (at the elbow only), and they performed
      movements over a fixed distance at three different speeds at the wrist and ankle.
      For fast movements we show that, in spite of some joint-specific differences, the
      basic pattern of electromyographic (EMG) modulation is similar at all three
      joints; for example, the agonist EMG burst transitions from a fixed duration to
      an increasing duration with increasing movement distance at all three joints.
      Moreover, the distance at which this transition occurs in one joint relative to
      the distance at which this transition occurs in the other two joints is
      consistent across subjects. The transition occurs at the shortest distance at the
      ankle and the longest distance at the wrist. In general we suggest that the data
      are consistent with a single set of control rules applied at all three joints,
      with the biomechanical constraints at each joint accounting for the differences
      in the EMG and kinematic patterns observed across joints.

PMID- 9547078
TI  - 5-Hydroxytryptamine modifies neuronal responses to glutamate in the red nucleus
      of the rat.
AB  - The effects of 5-hydroxytryptamine (5-HT) on the responses of red nucleus (RN)
      neurones to glutamate (glu) and its agonists were studied using a
      microiontophoretic technique in anaesthetised rats. Extracellular unitary
      recordings of RN neuronal activity showed that 5-HT application induced a
      significant and reversible depression of glu-evoked excitations in 85% of the RN
      units tested. This effect was independent of the action of the amine on
      background firing, which appeared enhanced in the majority of cases but was
      either depressed or uninfluenced in other cases. Microiontophoretic 5-HT also
      depressed the excitatory responses evoked in RN neurones by electrical
      stimulation of sensorimotor cortex. Methysergide application, which prevented the
      enhancing effects of 5-HT on the background firing, was scarcely effective in
      antagonising the depression of glu responses. In contrast, the serotonergic
      effects on the glu responses were reduced by the iontophoretically applied
      antagonist of 5-HT1A receptors, NAN-190. Microiontophoretic 5-HT was also able to
      influence the neuronal responses evoked by glu agonists quisqualate (quis) and N
      methyl-D-aspartate (NMDA), acting on non-NMDA and NMDA receptors respectively. In
      fact 5-HT depressed quis-evoked excitations and induced mixed effects on NMDA
      responses, which were reduced in 45%, enhanced in 34% and unmodified in 21% of
      the units tested. These results suggest that 5-HT is able to modulate the motor
      glutamatergic input to RN by acting mostly on non-NMDA receptors. The modulation
      of non-NMDA and NMDA receptors by 5-HT in the RN appears significant and its
      functional meaning is discussed.

PMID- 9547079
TI  - On the cutaneous receptors contributing to withdrawal reflex pathways in the
      decerebrate spinal rat.
AB  - Previous studies indicate that the withdrawal reflex system in the rat has a
      "modular" organization, each reflex pathway performing a specific sensorimotor
      transformation. Here, we wished to clarify which cutaneous receptors contribute
      to this system and to determine whether there are differences in this respect
      between reflex pathways of different muscles. Withdrawal reflexes of the peroneus
      longus, extensor digitorum longus, and semitendinosus muscles were recorded with
      EMG techniques during high reflex excitability in decerebrate spinal rats (n=26).
      While maintained innocuous pressure on glabrous skin could elicit a sustained
      reflex activity in all muscles studied, vibration of glabrous skin (10-300 Hz)
      always failed to evoke a reflex response, suggesting that slowly adapting, but
      not rapidly adapting, low-threshold mechanoreceptive fibers from this type of
      skin contribute to withdrawal reflex pathways. Thermal stimulation in the
      innocuous range, i.e., cooling from 32 to 17 degrees C, or warming the skin from
      32 to 41 degrees C, always failed to produce reflex responses, indicating that
      neither cold nor warm receptors contribute to withdrawal reflex pathways. When
      either cooling or warming the skin to the noxious temperatures of 1 degrees C or
      above 45 degrees C, respectively, a reflex discharge was often evoked in the
      muscles studied. Intradermal administration of histamine, a potent pruritogenic
      substance, produced very weak, or no, reflex response. In contrast, mustard oil
      produced vigorous reflex responses in all muscles studied. These findings suggest
      that some chemonociceptors contribute only weakly, or not at all, to withdrawal
      reflex pathways. The present data suggest that a selective set of cutaneous
      receptors contribute to withdrawal reflex pathways and that different withdrawal
      reflex pathways receive input from essentially the same cutaneous receptor types.

PMID- 9547080
TI  - Distinguishing between the effects of frequency and amplitude on interlimb
      coupling in tapping a 2:3 polyrhythm.
AB  - Rhythmic interlimb coordination is characterized by attraction to stable phase
      and frequency relations. Sudden, unintended transitions between such coordination
      patterns have been observed in iso- and multifrequency tasks when movement
      frequency was gradually increased. These transitions have been accounted for by
      modeling the two limbs as nonlinearly coupled oscillators. The prevailing form of
      the coupling function is based on time derivatives, but an alternative
      formulation can be derived by incorporating time delays. These time delays may be
      related to the neurophysiological delays associated with the use of kinesthetic
      afferences. The two ways of deriving coupling functions for interlimb
      coordination allow for different predictions with respect to the effects of
      movement frequency and amplitude on the strength of interaction between the
      limbs. In the current experiment, the effects of amplitude and frequency were
      dissociated experimentally, so as to arrive at an empirically motivated choice
      between the two ways of formalizing interlimb coupling. Subjects tapped the
      polyrhythm 2:3 at five different frequencies under three amplitude conditions.
      Whereas no effects of amplitude were observed, the strength of interaction
      between the hands decreased with increasing movement frequency. These results
      support the time-delay version of the model, in which differential (loss of)
      stability of coordination modes results from differential dependence on movement
      amplitude, but overall coupling strength is related reciprocally to movement
      frequency squared. This version of the model was related tentatively to three
      proposed aspects of interlimb coordination: (1) neurophysiological delays
      associated with the use of kinesthetic afferences; (2) rate-dependent decrease in
      pattern stability; and (3) differential entrainment influences of kinesthetic
      signals.

PMID- 9547081
TI  - Distribution, size and number of axons in the optic pathway of ground squirrels.
AB  - The present study has examined the distribution of axons of differing sizes in
      the optic pathway of the ground squirrel. Axon diameters were measured from
      electron micrographs at various locations across sections of the optic nerve and
      tract, and total distributions and numbers were estimated. In both the nerve and
      tract, roughly 1.2 million optic axons were present. The population of optic
      axons had a unimodal size distribution, peaking at 0.9 microm in diameter and
      having an extended tail toward larger diameters. Local axon diameter
      distributions in the optic tract indicated distinct (though partially
      overlapping) axon diameter classes, including one of fine sizes peaking at 0.8
      0.9 microm, a second of medium sizes peaking around 1.7-1.8 microm, and a third
      composed of the larger fibers with diameters up to 4.8 microm. The fine-caliber
      axons were found at all locations in the tract, and were the only axons present
      immediately adjacent to the pia, while the medium- and coarse-caliber axons were
      found at deeper locations. Curiously, the larger axons were found primarily in
      the medial parts of the tract, where axons from the dorsal retina normally
      course. A similarly restricted distribution of the larger axons was observed in
      the dorsotemporal parts of the optic nerve, suggesting that this difference in
      the tract may relate to an asymmetric distribution of ganglion cells on the
      retina giving rise to these axons. Measurements of axonal size taken within the
      optic fiber layer in dorsal and ventral parts of the retina confirmed this
      asymmetry, consistent with previous demonstrations of soma size differences in
      the dorsal versus ventral retina. The partial segregation of axons by size in the
      optic tract of the ground squirrel then reflects both the asymmetric distribution
      of retinal ganglion cell classes and the chronotopic reordering of optic axons
      that occurs within the chiasmatic region.

PMID- 9547082
TI  - The central pattern generator for vomiting may exist in the reticular area
      dorsomedial to the retrofacial nucleus in dogs.
AB  - There is some controversy over whether or not a discrete site that integrates
      vomiting activities in somatic and autonomic nerves is present in the medulla
      oblongata. On the basis of our previous studies, we hypothesized that the
      temporal patterns of muscle contractions in vomiting are generated by a central
      pattern generator in the retrofacial area of the rostral medulla. To investigate
      this hypothesis further, the effects of electrical and chemical lesions of the
      medullary area were observed in decerebrate paralyzed dogs. Efferent activities
      of the phrenic and abdominal muscle nerves were recorded to recognize fictive
      vomiting. The right half of the medulla oblongata was transversely severed about
      3 mm rostral to the obex. Fictive vomiting responses to vagal stimulation still
      appeared after hemisection in all 11 dogs. In addition, stimulation of the
      contralateral reticular area dorsomedial to the retrofacial nucleus produced
      fictive vomiting even after hemisection. An electrical lesion or injection of
      kainic acid (0.5-1.0 microl) was applied at the point where reticular stimulation
      induced fictive vomiting. After this destruction, no activities that corresponded
      to fictive vomiting could be induced by stimulation of vagal afferents or the
      reticular site. Salivation was decreased by hemisection, and decreased further,
      but was not completely abolished, with destruction of the reticular area. Kainic
      acid is known to selectively destroy neural cell bodies. Therefore, we concluded
      that neuronal somata in the reticular formation dorsomedial to the retrofacial
      nucleus play an essential role in the central patterning of vomiting activities
      in peripheral motor nerves.

PMID- 9547083
TI  - Development of action potentials and apamin-sensitive after-potentials in mouse
      vestibular nucleus neurones.
AB  - The postnatal maturation of medial vestibular nucleus (MVN) neurones was examined
      in slices of the dorsal brainstem prepared from balb/c mice at specific stages
      during the first postnatal month. Using spike-shape averaging to analyse the
      intracellularly recorded action potentials and after-hyperpolarizations (AHPs) in
      each cell, all the MVN neurones recorded in the young adult (postnatal day 30;
      P30) mouse were shown to have either a single deep AHP (type A cells), or an
      early fast and a delayed slow AHP (type B cells). The relative proportions of the
      two subtypes were similar to those in the young adult rat. At P5, all the MVN
      cells recorded showed immature forms of either the type A or the type B action
      potential shape. Immature type A cells had broad spontaneous spikes, and the
      characteristic single AHP was small in amplitude. Immature type B cells had
      somewhat narrower spontaneous spikes that were followed by a delayed, apamin
      sensitive AHP. The delayed AHP was separated from the repolarisation phase of the
      spike by a period of isopotentiality. Over the period P10-P15, the mean resting
      potentials of the MVN cells became more negative, their action potential fall
      times became shorter, the single AHP in type A cells became deeper, and the early
      fast AHP appeared in type B cells. Until P15 cells of varying degrees of
      electrophysiological maturity were found in the MVN but by P30 all MVN cells
      recorded were typical adult type A or type B cells. Exposure to the selective
      blocker of SK-type Ca-activated K channels, apamin (0.3 microM), induced
      depolarising plateaux and burst firing in immature type B cells at rest. The
      duration of the apamin-induced bursts and the spike frequency during the bursts
      were reduced but not abolished after blockade of Ca channels in Ca-free
      artificial cerebrospinal fluid containing Cd2+. By contrast, in mature type B
      cells at rest apamin selectively abolished the delayed slow AHP but did not
      induce bursting activity. Apamin had no effect on the action potential shape of
      immature type A cells. These data show that the apamin-sensitive I(AHP) is one of
      the first ionic conductances to appear in type B cells, and that it plays an
      important role in regulating the intrinsic rhythmicity and excitability of these
      cells.

PMID- 9547084
TI  - Time-course expression of vascular endothelial growth factor as related to the
      development of the retinochoroidal vasculature in rats.
AB  - Growth factors involved in angiogenesis are critical to both the normal and
      pathological vascular development in the retina and choroid. In the present
      experiment, the relationship between the vascular endothelial growth factor
      (VEGF) expression and the retinochoroidal vasculogenesis in Sprague-Dawley rats
      was investigated using in situ hybridization and immunohistochemistry. It was
      found that VEGF was produced mainly by astrocytes and Muller cells in the neural
      retina, and this was correlated temporally and spatially with the retinal
      vasculogenesis. In addition, it was observed that, although the VEGF expression
      in the retinal pigment epithelium (RPE) decreased with increasing age, it
      persisted from the embryonic stage to adulthood. These findings indicate that the
      VEGF expression in RPE may play a role in the development of the choroidal
      vessels as well as in the maintenance of the normal structure and permeability of
      the choriocapillaris in adults.

PMID- 9547085
TI  - Sinusoidal forearm tracking with delayed visual feedback. I. Dependence of the
      tracking error on the relative delay.
AB  - During forearm tracking of a sinusoidally moving target matching of
      proprioceptive and visual feedback was altered by introducing different visual
      delays. In five normal subjects seven target frequencies were tested ranging from
      0.3 to 1.5 Hz. For each target frequency nine different delays were used ranging
      from 0 to 120% of the cycle duration with target frequency and delay being varied
      randomly. Tracking error revealed a cyclic behaviour with an increase up to
      delays of about 50% of the target cycle duration and an improvement for delays
      larger than 50%. Modulation of response frequency was less pronounced compared
      with tracking error variation but also was dependent on relative phase. The
      response frequency matched the target frequency at delays of 0 and 100% of cycle
      duration and was slightly lower than the target frequency with relative delays of
      about 50%. The introduction of a visual delay during sinusoidal forearm tracking
      leads to a spatial in addition to the temporal mismatch between proprioception
      and vision. The temporal and the spatial incompatibility influence the tracking
      performance differentially.

PMID- 9547086
TI  - Sinusoidal forearm tracking with delayed visual feedback. II. Dependence of the
      relative phase on the relative delay.
AB  - The influence of delayed visual feedback on the phase relationships between
      target and response signal during a sinusoidal tracking task was analysed in five
      normal subjects. Target frequency was varied systematically between 0.3 and 1.5
      Hz, and the delay between 0 and 120% of the target cycle duration. For each
      subject, 63 trials were recorded. Phase parameters (relative phase, absolute
      relative phase and percentage of positive relative phases) revealed a clear
      dependence on relative delay but not on target frequency. With relative delays
      close to 0 and 100% of the target cycle duration, subjects successfully tracked
      the target signal with a small phase lag. With delays in the 30-90% range, larger
      phase differences were observed. Furthermore, the (delayed) response signal
      usually preceded the target signal in this delay range. These findings provide
      further evidence for a dependence of tracking error on external delays in the
      visual feedback loop, and indicate that delays of about 50% of the movement cycle
      are more difficult to handle than are smaller or larger delays. The results are
      discussed with regard to the influence of different control strategies (feedback,
      feedforward) and different types of feedback (such as vision and proprioception)
      on motor control.

PMID- 9547087
TI  - Somatotopic consolidation: a third phase of reorganization after peripheral nerve
      injury in adult squirrel monkeys.
AB  - It has previously been demonstrated that the central somatosensory topographic
      reorganization within deprived cortex that follows peripheral nerve injury in
      adult monkeys occurs in at least two stages: an immediate unmasking period; and a
      more prolonged period where deprived areas of cortex come to express new
      receptive fields in a topographically arranged manner. In the present
      experiments, we have compared cortical topography many months after combined
      median and ulnar nerve transection with "complete" reorganization evident at
      relatively short (i.e., 2-5 months) survival times. We find further
      reorganizational changes in cortical topography with longer survival times. That
      is, the roughly somatotopic, generally multiple-digit receptive fields frequently
      observed at the shorter survival times are generally sharpened to more distinct,
      single-digit receptive fields at longer survival times. We hypothesize that the
      early crudely topographic maps reflect all available inputs while the refined map
      is the outcome of an extraction process where only the most useful subset of
      available inputs is expressed. It is further suggested that this distillation
      process is a use-dependent phenomenon.

PMID- 9547088
TI  - Effects of repetitive transcranial magnetic stimulation over dorsolateral
      prefrontal and posterior parietal cortex on memory-guided saccades.
AB  - We investigated the role of the dorsolateral prefrontal cortex (DLPFC) and the
      posterior parietal cortex (PPC) in a visuospatial delayed-response task in
      humans. Repetitive transcranial magnetic stimulation (20 Hz, 0.5 s) was used to
      interfere temporarily with cortical activity in the DLPFC and PPC during the
      delay period. Omnidirectional memory-guided saccades with a 3-s delay were used
      as a quantifiable motor response to a visuospatial cue. The question addressed
      was whether repetitive transcranial magnetic stimulation (rTMS) over the DLPFC or
      PPC during the sensory of memory phase affects accuracy of memory-guided
      saccades. Stimulation over the primary motor cortex served as control.
      Stimulation over the DLPFC significantly impaired accuracy of memory-guided
      saccades in amplitude and direction. Stimulation over the PPC impaired accuracy
      of memory-guided saccades only when applied within the sensory phase (50 ms after
      cue offset), but not during the memory phase (500 ms after cue offset). These
      results provide further evidence for a parieto-frontal network controlling
      performance of visuospatial delayed-response tasks in humans. It can be concluded
      that within this network the DLPFC is mainly concerned with the mnemonic
      representation and the PPC with the sensory representation of spatially defined
      perceptual information.

PMID- 9547089
TI  - The NMDA receptor participates in respiration-related mitral cell synchrony.
AB  - The N-methyl-D-aspartate (NMDA)-type glutamate receptor participates in the
      excitation of olfactory bulb mitral cells and is important in granule-cell
      mediated feedback-inhibition. In the present study, extracellular unit recordings
      were made in vivo to demonstrate that the firing rates of mitral cells are not
      affected by peripheral administration of the non-competitive NMDA receptor
      antagonist MK-801. However, while over 50% of odor-driven mitral cell activity is
      normally correlated with the respiratory cycle, only about 10% of mitral cell
      activity is correlated with the respiratory cycle 30 min after MK-801
      administration. Thus, the NMDA receptor is a participant in normal respiration
      related mitral cell activity and may have an important role in the formation of
      bulb oscillations that encode olfactory information. Furthermore, the NMDA
      receptor is in a position to mediate activity-dependent changes in the bulb that
      rely on synchronous activity.

PMID- 9547090
TI  - Axial synergies during human upper trunk bending.
AB  - Upper trunk bending movements were accompanied by opposite movements of the lower
      body segments. These axial kinematic synergies maintained equilibrium during the
      movement performance by stabilizing the center of gravity (CG), which shifted on
      average across all the subjects by 1 +/- 4 cm in the anteroposterior direction
      and thus always remained within the support area. The aim of the present
      investigation was to provide an insight into the central control responsible for
      the performance of these synergies. The kinematic analysis was performed by the
      method of principal components (PC) analysis applied to the covariation between
      ankle, knee and hip joint angles and compared with CG shifts during upper trunk
      bending. Subjects were asked to perform backward or forward upper trunk bending
      in response to a tone. They were instructed to move as fast as possible or slowly
      (2 s), with high or low movement amplitudes. PC analysis showed a strong
      correlation between hip, knee and ankle joint changes. The first principal
      component (PC1) representing a multijoint movement with fixed ratios between
      joint angular changes, accounted, on average, for 99.7% +/- 0.2% of the total
      angular variance in the forward trunk movements and for 98.4% +/- 1.4% in the
      backward movements. The instructed voluntary regulation of the amplitude and
      velocity of the movement was achieved by adapting the bell-shaped profile of the
      velocity time course without changes in interjoint angular relations. Fixed
      ratios between changes in joint angles, represented by PC1, ensured localization
      of the CG within the support area during trunk bending. The ratios given by PC1
      showed highly significant dependence on subjects, suggesting the adaptability of
      the central control to each subject's biomechanical peculiarities. Subject's
      intertrial variability of PC1 ratios was small, suggesting a stereotyped
      automatic interjoint coordination. When changing velocity and amplitude of the
      movement, the ratios remained the same in about half the subjects while in others
      slight variations were observed. A weak second principal component (PC2) was
      shown only for fast movements. In forward movements PC2 reflected the early knee
      flexion that seems related to the disturbances caused by the passive interaction
      between body segments, rather than to the effect of a central command. In fast
      backward movements, PC2 reflected the delay in hip extension relative to the
      movement onset in the ankle and knee that mirrors intersubject differences in the
      initiation process of the axial synergy. The results suggest that PC1 reflects
      the centrally controlled multijoint movement, defining the time course and
      amplitude of the movement and fixing the ratios between changes in joint angles.
      They support the hypothesis that the axial kinematic synergies result from a
      central automatic control that stabilizes the CG shift in the anteroposterior
      direction while performing the upper trunk bending.

PMID- 9547092
TI  - Functional evidence for the differential control of superficial and deep blood
      vessels by sympathetic vasoconstrictor and primary afferent vasodilator fibres in
      rat hairless skin.
AB  - We quantitatively investigated sympathetic vasoconstriction and antidromic
      vasodilation mediated by small-diameter primary afferents on the plantar hairless
      skin of the hindpaws in Wistar rats using laser Doppler (LD) flowmetry and an
      infrared thermometer. Sympathetic vasoconstriction was elicited by electrical
      stimulation of the centrally cut ipsilateral lumbar sympathetic trunk (LST) with
      50-s trains at 0.1-20 Hz. Antidromic vasodilation was evoked by electrical
      stimulation of the dorsal root (DR) L5 with 20-s or 50-s trains at 1-4 Hz.
      Cutting the LST resulted in increases in skin temperature (SKT) by 6.1 +/- 1.0
      degrees C (mean +/- SEM) and in LD flow by 128 +/- 20%. Stimulation of the LST
      resulted in a graded decrease in LD flow and SKT that was most pronounced between
      0 and 0.1 Hz. However, DR stimulation evoked a large increase in LD flow but only
      little change in SKT in rats with sectioned LST. When the DR was stimulated
      either in animals with intact LST or during continuous stimulation of
      vasoconstrictor fibres in the sectioned LST, i.e. while baseline temperature was
      relatively low (26.3 +/- 1.1 degrees C), DR stimulation still resulted in large
      increases in LD flow, but only minor changes in SKT. These results suggest that
      blood flow through both deep and superficial layers of rat hairless skin is
      regulated by activity in sympathetic postganglionic vasoconstrictor fibres,
      whereas small-diameter primary afferent fibres appear to influence predominantly
      the blood flow through superficial layers of rat plantar skin.

PMID- 9547091
TI  - The gap effect and express saccades in the auditory modality.
AB  - Latencies of eye movements to peripheral targets are reduced when there is a
      short delay (typically 200 ms) between the offset of a central visual fixation
      point and the target onset. This has been termed the gap effect. In addition,
      some subjects, usually with practice, exhibit a separate population of very short
      latency saccades, called express saccades. Both these phenomena have been
      attributed to disengagement of visual attention when the fixation point is
      extinguished. A competing theory of the gap effect attributes it to disengagement
      of oculomotor fixation during the temporal gap. It is known that auditory targets
      are effective in eliciting saccadic eye movements, and also that covert attention
      operates in the auditory modality. If the gap effect and express saccades are due
      to disengagement of spatial attention, both should persist in the auditory
      modality. However, fixation of gaze is largely under visual control. If the gap
      effect results from disengagement of fixation, then at least a reduced effect
      should be seen in the auditory modality. Human subjects performed the gap task
      and a control task in the dark, using auditory fixation points and saccadic
      targets, on five successive days. Despite this practice, express saccades were
      not observed. There was a reliable gap effect, but the reduction in saccadic
      latency was only 17 ms, compared with 32 ms for the same subjects in the visual
      modality. This suggests that about half the gap effect is due to disengagement of
      visual fixation. The remainder was not due to non-specific warning effects and
      could be attributed to offset of the auditory fixation stimulus.

PMID- 9547093
TI  - Induction of microglial and astrocytic response in the adult rat lumbar spinal
      cord following middle cerebral artery occlusion.
AB  - The response of microglia and astrocytes, as detected immunohistochemically by
      the monoclonal antibody OX-42 and anti-glial fibrillary acidic protein (GFAP)
      respectively, was studied in the rat lumbar spinal cord following focal cerebral
      ischaemia produced by permanent occlusion of the middle cerebral artery (MCA)
      above the rhinal fissure. At 1 and 2 days after right-sided MCA occlusion, OX-42
      immunoreactivity of microglia in both the contralateral dorsal and ventral horns
      of the lumbar spinal cord was moderately increased compared with cells of the
      ipsilateral side. The microglial reaction was progressive, with some cells
      transformed into amoeboid form considered to be macrophages at day 3. By 5 days,
      many of the reactive microglia, notably in the ventral horn, appeared to encircle
      the soma of motoneurons. At 7 days, the microglial reaction had subsided while
      astrocytes in the same area were hypertrophied to replace the perineuronal
      microglia. The microglial response in both the cerebral cortex and lumbar spinal
      cord was effectively reduced by the N-methyl-D-aspartate (NMDA) receptor
      antagonist, MK-801. Present results suggest that following MCA occlusion, the
      vigorous response of microglia, and subsequently astrocytes, in the spinal cord
      in extra-focal areas far removed from the primary site of ischaemia may be
      mediated by glutamate released from the ischaemic corticospinal neurons through
      NMDA receptors on the postsynaptic spinal cord neurons.

PMID- 9547094
TI  - Analysis of double-joint movements in controls and in parkinsonian patients.
AB  - The motor performance of seven patients with Parkinson's disease and seven
      control subjects was tested in a choice reaction aiming task. The subjects were
      instructed to aim as fast and as accurately as possible to a light stimulus,
      which defined one of eight possible target positions. In order to reach the
      targets, elbow flexions had to be combined with forearm supinations or with
      forearm pronations. For single-joint movements, forearm supinations or pronations
      were executed faster than the long elbow flexions in both groups. In the double
      joint movements of the control group, the flexion movement times (flex.MTs) and
      the supination movement times (sup.MTs) or pronation movement times (pron.MTs)
      were similar to the MTs of the corresponding single-joint movements. MTs of
      parkinsonian patients were significantly longer than those of control subjects.
      MTs were most increased in the forearm supination and forearm pronation of double
      joint movements. In contrast to the controls, sup.MT and pron.MT were
      significantly increased in double-joint movements as compared to single-joint
      movements. The variations in the flex.MT and sup.MT of the double-joint movements
      neither correlated for a control subject nor for a parkinsonian patient. For
      controls, the independent MTs in double-joint movements cannot be explained by
      minimal principles (minimum energy, minimal torque change), but suggest that two
      separate motor programs are superimposed. In Parkinson's disease, there seems to
      be a deficit in superimposing two separate motor programs.

PMID- 9547095
TI  - Reach-to-grasp movements during obstacle avoidance.
AB  - The transport and grip components are two controlled components of a prehensile
      movement. These components are coordinated so that objects of varying size and
      shape resting in diverse locations can be grasped easily. It has been suggested
      that the timing between these two components is a specified parameter, although
      the origin of such timing is unknown. The present study examines the
      interdependency of the reach and grasp components when the transport component is
      modified by placing an obstacle of varying height (9 cm and 11 cm) in the hand
      path between the starting position and the target object location. Subjects were
      asked to reach over a Plexiglas barrier and grasp a 2-cm dowel. To reach the
      object, the subject had to elevate the hand. At issue in this experiment is
      whether changes in hand path trajectory caused by obstacle avoidance produce
      corresponding changes in the kinematics of grip aperture. The findings showed
      that reaching in the presence of an obstacle resulted in the prolongation of most
      transport component time parameters except peak acceleration and a few amplitude
      parameters. Changes in the transport component also produced systematic
      prolongation in all time parameters of grip kinematics, including grip closure
      time. Temporal prolongation was also reflected in a significant decrease in grip
      opening and closing velocity; only relative time-to-peak closing velocity was
      maintained. Closure distance and maximum grip aperture were smaller for the
      obstacle conditions. Together with the observed smaller variability for the
      distance to peak aperture, these findings suggest that spatial localization of
      the hand aperture is an important prehensile movement control feature.
      Parameterization processes for the grip component are closely linked to those of
      the transport component, and their organization appears to be interdependent.

PMID- 9547096
TI  - Evidence that spinal endogenous opioidergic systems control the expression of
      chronic pain-related behaviors in spinally injured rats.
AB  - We have previously reported that ischemic spinal cord injury in rats leads to
      chronic pain-related behaviors. Thus, rats exhibited aversive reactions to
      innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or
      rostral to the dermatomes innervated by the injured spinal segments. The
      responses of the rats to cold are also markedly enhanced (cold allodynia).
      Interestingly, more than 50% of spinally injured rats did not develop these
      abnormal pain-related behaviors after spinal cord injury. In the present study,
      we showed that the extent of injury is similar between allodynic and non
      allodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid
      receptor antagonist, reversibly provoked mechanical and cold allodynia-like
      responses in spinally injured rats that did not develop such behaviors
      spontaneously. However, naloxone did not elicit such reactions in normal rats and
      did not alter the tail-flick latency in normal or spinally injured rats.
      Furthermore, i.t. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole,
      selective antagonists of mu and delta opioid receptors, respectively, also
      triggered pain-related behaviors similarly to naloxone. Although
      norbinaltorphimine (nor-BIN), a selective kappa-receptor antagonist, also
      elicited such responses, the time course of the effect makes it unlikely that
      spinal kappa-receptors were involved. These results suggested that the expression
      of abnormal pain-related behaviors in some spinally injured rats is tonically
      suppressed by the spinal opioidergic system. Interindividual differences that
      lead to lack or dysfunction of such inhibition may underly the appearence of pain
      related behavior in some, but not all, spinally injured rats. It is suggested
      that such inhibition is exerted through spinal mu and delta, but not kappa,
      opioid receptors. The endogenous opioidergic control appears to be only active
      against abnormal painrelated behaviors in spinally injured rats. Our results are
      relevant for the clinical observation that only a subgroup of patients with nerve
      injury suffers from neuropathic pain.

PMID- 9547097
TI  - A comparison of jaw-opener and jaw-closer muscle activity in humans to overcome
      an external force counteracting jaw movement.
AB  - In contrast to the jaw-closer muscles, no or very few spindles are present in the
      jaw-opening digastric muscle. Therefore sensory feedback to the digastric muscle
      may be different from feedback to the jaw-closer muscles, resulting in a
      different reaction when jaw movement is perturbed. This possible difference was
      investigated by comparing the reaction of the digastric muscle when jaw opening
      is perturbed, with the reaction of the masseter muscle when jaw closing is
      perturbed. Subjects made rhythmic, 1-Hz open-close movements of the jaw under
      control of a metronome. During jaw opening (digastric muscle) or, in the other
      experiments, during jaw closing (masseter muscle), an external force
      counteracting jaw movement could appear. Series of movements without the force
      were unexpectedly alternated by series with the force. In both muscles sensory
      induced activity started approximately 25 ms after the onset of the force and
      consisted of two phases. In the masseter muscle the maximum of the first increase
      was reached significantly sooner (37 +/- 2 ms SEM) than in the digastric muscle
      (54 +/- 3 ms). The second increase appeared much sooner in the masseter muscle
      (73 +/- 4 ms) than in the digastric muscle (159 +/- 10 ms). When the force was
      expected, in both muscles an increase in preprogrammed muscle activity was
      observed. Also an increase in reflex activity, generated before 120 ms after the
      onset of the force, was observed, compared with when the force appeared
      unexpectedly. The relative increase in reflex activity was approximately 2 times
      larger than the relative increase in preprogrammed activity. Therefore, the
      increase in reflex activity when the force was expected may have been caused not
      only by an increase in recruitment, but also by an increase in the gain of the
      reflex loops. Reflex activity relative to preprogrammed activity was on average 4
      times larger in the masseter muscle than in the digastric muscle. This indicates
      that the masseter muscle can react more adequately to disturbances of jaw
      movement than the digastric muscle.

PMID- 9547098
TI  - Receptive field properties of visual neurons in the avian nucleus lentiformis
      mesencephali.
AB  - The receptive field (RF) properties of visual neurons extracellularly recorded
      from the nucleus lentiformis mesencephali (nLM) in pigeons (Columba livia) were
      quantitatively analyzed using a workstation computer. These cells were actively
      spontaneous, and direction-and velocity-selective. Using spatial gratings as
      visual stimuli, these cells could be divided into three groups: uni- (74%), bi-
      (17%), and omnidirectional (9%) cells in terms of their directionality. On the
      basis of their velocity selectivity, they could be named slow cells (84%),
      preferring low velocity (0.1-11 degrees/s), and fast cells (14%), preferring
      rapid motion (34-67 degrees/s), with one cell (2%) responding maximally to an
      intermediate velocity of 18 degrees/ s. These two properties were correlated in
      the way that all unidirectionals were slow cells, omnidirectionals were fast
      cells, and bidirectionals were either slow or fast cells including the
      intermediate cell. Using small targets as visual stimuli, it was found that the
      majority of cells examined had RFs that each consisted of an excitatory RF (ERF)
      and an inhibitory RF (IRF) that overlapped. The unidirectionals were mainly of
      this type of RF structure, whereas the omnidirectionals apparently had ERFs
      alone. The direction preference of ERF was opposite to that of IRF for
      unidirectional cells tested, whereas they were perpendicular to each other for
      one bidirectional cell. The overall responses of these cells resulted from
      interaction between excitation and inhibition induced by directionally different
      motion. Under certain conditions, visual responses of a particular cells to a
      small target moving through its ERF were equal in responsive strength to those to
      whole-field gratings swept over the screen. It was suggested that optokinetic
      nystagmus produced by wholefield gratings results from population activity of
      large group(s) of neurons in some optokinetic nuclei, at least one of which is
      nLM.

PMID- 9547099
TI  - Coordination of hand aperture with the spatial path of hand transport.
AB  - We have investigated the coordination of hand aperture with the spatial path of
      hand transport in prehensile movement by comparing straight prehensile movements
      with curved movements, in which subjects had to pass over a "via point" marked on
      the work surface before picking up an object in the target location. Spatial
      plots of hand aperture against hand transport showed that the preshaping of the
      hand to prepare an appropriate grasp was delayed in the curved movements relative
      to the straight movements, with most of the preshaping of the hand occurring
      after passing the via point, even when the via point occurred late in the course
      of the movement. The postponement of hand preshaping was apparently not due to
      subjects' segmenting the movement into two completely separate portions preceding
      and following the via point, since some degree of hand opening often occurred
      before the via point. We suggest that the delay in hand opening in curved
      movements involves a scheduling process, which uses information about hand
      transport to set an appropriate hand aperture.

PMID- 9547101
TI  - Helicobacters and biliary tract disease.

PMID- 9547100
TI  - Regulation of hepatic chylomicron remnant uptake: effects of obesity and insulin
      resistance.

PMID- 9547102
TI  - Steatohepatitis: a tale of two "hits"?

PMID- 9547103
TI  - Recurrent bleeding from peptic ulcers: sticky problem, sticky solution?

PMID- 9547104
TI  - Evaluating TIPS trials: the devil is in the details?

PMID- 9547105
TI  - Gastroesophageal reflux-induced asthma: new insights.

PMID- 9547106
TI  - One if by mouth and two if IV.

PMID- 9547107
TI  - 13C-Octanoic acid breath test for gastric emptying rate of solids.

PMID- 9547108
TI  - 13C-Octanoic acid breath test: valueless test for gastric emptying?

PMID- 9547109
TI  - Pancreatic disease: does "itis" lead to "oma"?

PMID- 9547110
TI  - Unreliable pancreatitis epidemiology captures the wrong population.

PMID- 9547111
TI  - Treatment of short-bowel syndrome.

PMID- 9547112
TI  - Arterioportal fistula in a child with biliary atresia.

PMID- 9547113
TI  - Are normal hearing thresholds a sufficient condition for click-evoked otoacoustic
      emissions?
AB  - Transiently evolked otoacoustic emissions (TEOAE) have been reported in several
      studies as absent in a small minority of normal ears. Other studies have reported
      TEOAEs in all normal ears. Differences between studies may arise directly from
      criteria for TEOAE identification, criteria for selection of normals, or
      statistically due to limited sample sizes. In order to understand and model
      cochlear processes involved in TEOAE generation, it needs to be known whether the
      presence of normal hearing leads automatically to generation of TEOAEs. The
      present study set out to establish in a large sample if any ears could be found
      that lacked TEOAEs despite normal hearing threshold levels (HTL). A total of 397
      ears from highly cooperative adult subjects were examined under laboratory
      conditions. Using cross correlation between replicate nonlinear waveforms as the
      criterion, TEOAEs were present in 99.2% of the sample (lower CI 98.1%). However,
      careful visual assessment of the recorded waveforms for the remaining ears did
      not unequivocally show absence of TEOAE characteristics in any ear with normal
      HTLs. While TEOAE strength varies widely among ears, no clear evidence was found
      to show that TEOAEs can be absent when HTLs are normal.

PMID- 9547114
TI  - Treatment resistant depression in the elderly: a review of its conceptualisation,
      management and relationship to organic brain disease.

PMID- 9547115
TI  - Disinhibition syndromes, secondary mania and bipolar disorder in old age.
AB  - BACKGROUND: The neurological literature concerning disinhibition syndromes and
      secondary mania has run in parallel to clinical reports of bipolar disorder in
      old age. METHODS: A critical review was conducted of both the neurological and
      geriatric psychiatry literature in an attempt to integrate the two streams.
      RESULTS: Disinhibition syndromes include lateralization to the right hemisphere
      and localization of lesions to the orbito-frontal and basotemporal cortex
      involving limbic and frontal connections (orbito-frontal circuit). Mania in old
      age is associated with late onset, heterogeneous neurological disorders and poor
      outcome. CONCLUSION: Bipolar disorders in old age may be understood in the
      context of affective vulnerability influenced by a specific neurobiologic
      substrate. LIMITATIONS: The clinical literature consists predominantly of small
      case series and anecdotal reports. CLINICAL RELEVANCE: Improved understanding of
      these syndromes may elucidate the pathogenesis and etiology of bipolar disorders
      and the neuropsychiatric syndromes affecting mood, motivation and behavioural
      disinhibition.

PMID- 9547116
TI  - Anxiety disorders in the elderly: DSM-IV and other barriers to diagnosis and
      treatment.
AB  - Traditional lore suggests that anxiety disorders are less prevalent in elderly
      than in younger adults, and late-onset anxiety disorders are especially rare. We
      question these assumptions, and suggest that these conditions are underdiagnosed
      in late life. A common problem in the literature is the application of DSM-IV
      like criteria developed from studies of younger adults to geriatric samples
      without regard for atypical symptom presentations, high occurrence of depressive
      and medical co-morbidity, and influence of aging-related psychosocial changes on
      the clinical picture. Diagnostic problems are further compounded by therapeutic
      ones. Clinicians are often forced to make treatment decisions for their elderly
      patients based on uncontrolled clinical observations or questionable
      extrapolation of treatment data in younger adults. An open-minded approach
      unhinged by 'conventional wisdom' is warranted.

PMID- 9547117
TI  - The efficacy, safety and tolerability of antidepressants in late life depression:
      a meta-analysis.
AB  - BACKGROUND: To determine the efficacy, safety and tolerability of antidepressants
      in depressed elderly patients. METHODS: Search for randomized controlled double
      blind studies evaluating atypical antidepressants (ATYPs), reversible inhibitors
      of monoamine oxidase-A, selective serotonin reuptake inhibitors (SSRIs) and
      tricyclic antidepressants in moderate/severe depressed patients > or = 60 years
      for > or = four weeks. The random effects model (single-arm; comparative) was
      used to aggregate efficacy, safety and dropout. RESULTS: No difference in single
      arm aggregation of outcomes for four antidepressant classes. Comparative analyses
      showed no statistical difference between outcomes, except SSRIs had a higher
      response rate than ATYPs. CONCLUSION: Elderly show no differences in
      antidepressant class outcomes. LIMITATIONS: Heterogeneity and lack of power.
      CLINICAL RELEVANCE: There is little advantage for antidepressant classes over
      another in the aged.

PMID- 9547119
TI  - Depression, diagnostic sub-type and death: a 25 year follow-up study.
AB  - We assessed mortality rates over 25 years in 212 patients admitted for depression
      or depressive symptoms. More patients had died than expected (80 including 13
      suicides; SMR = 1.40, P < 0.01). Females, but not males, experienced
      significantly higher mortality than the general population. When suicides were
      excluded, neither the group as a whole, nor females solely, demonstrated excess
      mortality. Rigorously diagnosed depressive sub-type did not predict mortality.
      Mortality, particularly from suicide, was disproportionately greater in the first
      2 years after index admission, suggesting that the follow-up of patients
      hospitalised with depression must be especially assiduous during the years
      immediately after admission.

PMID- 9547118
TI  - Depression and physical health in later life: results from the Longitudinal Aging
      Study Amsterdam (LASA).
AB  - BACKGROUND: In later life, declining physical health is often thought to be one
      of the most important risk factors for depression. Major depressive disorders are
      relatively rare, while depressive syndromes which do not fulfill diagnostic
      criteria (minor depression) are common. METHODS: Community-based sample of older
      adults (55-85) in the Netherlands: baseline sample n = 3056; study sample in two
      stage screening procedure n = 646. Both relative (odds ratios) and absolute
      (population attributable risks) measures of associations reported. RESULTS: In
      multivariate analyses minor depression was related to physical health, while
      major depression was not. General aspects of physical health had stronger
      associations with depression than specific disease categories. Significant
      interactions between ill health and social support were found only for minor
      depression. Major depression was associated with variables reflecting long
      standing vulnerability. CONCLUSION: Major and minor depression differ in their
      association with physical health. LIMITATION: Cross-sectional study relying
      largely on self-reported data. CLINICAL RELEVANCE: In major depression, with or
      without somatic co-morbidity, primary treatment of the affective disorder should
      not be delayed. In minor depression associated with declining physical health,
      intervention may be aimed at either or both conditions.

PMID- 9547120
TI  - Depression in male geropsychiatric inpatients with and without dementia: a
      naturalistic study.
AB  - The authors compared the presentation and course of major depression in male
      geriatric inpatients with and without a diagnosis of dementia. Of 326 consecutive
      admissions to an inpatient geropsychiatry unit, 22 (7%) had a diagnosis of major
      depression without dementia, 35 (11%) had major depression with dementia. Both
      groups presented with similar types and severity of depressive symptoms, which
      improved substantially with treatment in both groups, as measured by Hamilton
      Depression Rating Scale scores. In addition, agitation, psychiatric, and side
      effects symptoms decreased significantly in both groups. Our naturalistic results
      suggest the clinical value of intensive treatment of depressive symptoms in
      elderly demented patients, whether or not they meet the criteria for major
      depressive episode.

PMID- 9547121
TI  - Co-occurrence of disadvantage conditions in elderly subjects with depressive
      symptoms.
AB  - The aim of this survey study is to describe the association of symptomatic
      depression with the co-occurrence of psycho-social, functional, and somatic
      disadvantage conditions in 390 over 70 subjects living at home. The most
      disadvantaged tertile of various conditions (age, social support, cognition,
      social interactions, self evaluation of health, disability, number of diseases,
      and somatic symptoms) was associated with greater risk of symptomatic depression.
      A subset of conditions that might be causally related to depression (age, social
      support, financial welfare, diseases, and disability) was used to divide subjects
      into five levels of increasing multiple disadvantage conditions (MDC). Increasing
      severity of MDC level was associated with greater risk of symptomatic depression
      even after adjustment for gender and all five conditions used to define MDC
      levels (odds ratios ranging from 2.7 to 11.3).

PMID- 9547123
TI  - Changes in auditory P300 in patients with major depression and silent cerebral
      infarction.
AB  - We examined event-related potentials in patients with senile depression and
      silent cerebral infarction (SCI) to clarify the features of the P300 component.
      P300 event-related potentials were recorded in drug-free depressed patients (N =
      16) and normal controls (N = 17). All patients underwent magnetic resonance
      imaging and were classified as SCI-positive (N = 7) or SCI-negative (N = 9). In
      depressed patients, the P300 was reexamined after antidepressant treatment. Prior
      to treatment, P300 amplitudes in depressed patients were significantly smaller
      than those in normal controls (P < 0.01). P300 amplitudes increased significantly
      in SCI-negative patients following recovery (P < 0.05), but did not change in SCI
      positive patients. SCI may interrupt the treatment-related P300 amplitude
      increase in depressed patients.

PMID- 9547122
TI  - The natural history of depression and the anxiety disorders in older people: the
      Islington community study.
AB  - BACKGROUND: This study reports the outcome of depression and anxiety disorders in
      older people. METHODS: Follow-up of 165 subjects age 65 or over, initially
      identified in a community study in inner London as depressed or having an anxiety
      disorder. RESULTS: 117 subjects still living in the area; 25 had died. Death was
      predicted only by activity limitation at first interview and not by other
      demographic or morbidity variables. Eighty-six subjects reinterviewed; 21 males,
      65 females. Of the depressed, 34% had recovered, 39% were depressed and 27% were
      dead. Predictors from initial interview of continuing depression were female
      gender and more severe depression. Of those with phobic anxiety, 16% had
      recovered, 18% died and 66% were still phobic. Predictors of continuing phobic
      anxiety from initial interview were female gender and "stand-alone" phobic
      anxiety, i.e., not being depressed at initial interview. Sixty percent of those
      with early onset phobias had specific phobias; 82% of those with late-onset
      phobias had agoraphobia. Twenty-two subjects were prescribed psychotropics. The
      only significant predictor of psychotropic prescription was having sleep
      disturbance at initial interview. A low score on life satisfaction was
      significantly correlated with depression but not with phobic disorder. A high
      score was correlated with not having a current psychiatric disorder. LIMITATIONS:
      Some subjects were lost to follow-up. Those on psychotropics were particularly
      likely to refuse an interview. CONCLUSION AND CLINICAL RELEVANCE: In older
      people, neither depression nor the anxiety disorders generally remit
      spontaneously. Those with a particularly poor prognosis are women and those with
      a more severe depression. Agoraphobia may be precipitated in older people by
      stressful events and interferes with life satisfaction. There is potential for
      increased pharmacological treatment of older people with affective disorders.

PMID- 9547124
TI  - Ruminative thinking in older inpatients with major depression.
AB  - Ruminative thinking, the tendency to dwell on particular ideas or themes, can be
      a prominent part of the phenomenology of major depression, but it rarely has been
      the focus of empirical research. We attempted to replicate (in adult psychiatric
      inpatients age > or = 50 years with DSM-III-R major depression) the previously
      published finding that ruminative thinking was associated with melancholia and
      with psychosis. In our sample, these associations were not present. In addition,
      we explored the relationships of ruminative thinking to specific areas of thought
      content (e.g., suicidal ideation, somatic worry), cognitive function and overall
      functional status; ruminative thinking was not associated with suicidal ideation,
      but was associated with greater somatic worry and with poorer functional status,
      although these associations were not independent of overall depressive severity.
      A substantial proportion of subjects were unable to complete the cognitive
      measures; ruminative thinking was independently associated with inability to
      complete these tasks. We conclude that ruminative thinking is a meaningful and
      common clinical phenomenon among severely depressed older inpatients. Further
      investigations in inpatients and other populations examining its relationships to
      other phenomenology, to course and outcome, and to putative underlying mechanisms
      of depression are warranted.

PMID- 9547125
TI  - An intervention study with husband and wife carers of older people with a
      psychiatric illness.
AB  - BACKGROUND: Individual packages of care were devised for spouses of older people
      with psychiatric illness. METHOD: Randomised controlled trial with blind follow
      up. Intervention group members were offered multidisciplinary packages while
      controls received no extra help. Both groups were reassessed 12-14 weeks later.
      The initial control group then received intervention; both were reassessed at 24
      28 weeks. RESULTS: Although no significant differences emerged in group mean
      scores for affective illness or social difficulties, carers who were mentally ill
      at outset improved significantly. CONCLUSION: Interventions targeted at
      caregiving spouses with affective disorder are acceptable and efficacious.
      LIMITATION: It was impossible to compare treatment with no treatment.

PMID- 9547126
TI  - Effects of comorbidity and polypharmacy on the clinical usefulness of sertraline
      in elderly depressed patients: an open multicentre study.
AB  - Antidepressant therapy in the elderly age group is frequently complicated by
      medical comorbidity, polypharmacy and increased sensitivity to drug effects. A
      nonblind, noncomparative, observational, multicentre study over 8 weeks was
      conducted to assess the effectiveness and tolerability of sertraline (50-200
      mg/day) in 1437 elderly depressed outpatients with a mean (S.D.) age of 68 (6.3)
      years (range 60-92) in routine clinical practise. Depressive symptoms were
      monitored using the Montgomery Asberg Depression Rating Scale (MADRS) at baseline
      and at weeks 2, 4, 6 and 8. The mean dose of sertraline at the final visit was
      85.2 mg/day (48% of patients were given the initial dose throughout the study).
      At the end of the study, mean percentage change of MADRS score from baseline was
      61% (P < 0.001). A > or = 50% decrease in MADRS score was obtained in 70% of
      patients. Sertraline was well tolerated. Side effects occurred in 23% of
      patients, although only 5.1% withdrew because of adverse events. There were no
      significant differences in the antidepressant effectiveness or occurrence of side
      effects when patients with and without concomitant pathologic conditions or with
      and without concurrent medications were compared. These findings indicate the
      absence of clinically important drug interaction and confirm the effectiveness
      and safety of sertraline in routine clinical practise for treating elderly
      depressed outpatients.

PMID- 9547127
TI  - Long-term treatment of geropsychiatric depressed patients with venlafaxine.
AB  - Twenty-eight psychiatric patients older than 65 years with major depression with
      high probability of recurrence were enrolled in a 24-month open label clinical
      trial aimed at evaluating the long-term efficacy and safety of venlafaxine. All
      patients completed the acute phase of the study; 21 were responders and entered
      the follow-up period. During the continuation phase no relapse was observed.
      During the maintenance period, 20% of the patients had a single new recurrence.
      No significant side effects were observed. The results demonstrate that
      venlafaxine is both effective and safe in the long-term treatment of major
      depression in geropsychiatric patients.

PMID- 9547128
TI  - Are personality disorders more frequent in early onset geriatric depression?
AB  - This preliminary study evaluates the prevalence of personality disorders (PD) in
      a sample of 37 elderly recovered depressed and non-demented patients, using the
      French version of the Vragenlijst voor Kenmezken van de Persoonlijkheid (VKP) or
      Questionnaire on Personality Traits (QPT). The prevalence of definite personality
      disorder was 65% with predominance of Cluster C and particularly dependent and
      avoidant PD. The rate of PDs was higher in early onset (73%) than in late onset
      (45%) geriatric depression, even though there is only a trend towards statistical
      significance (Chi square = 2.588, p = 0.107). These results are consistent with
      those of previous reports using different PD assessment methods, supporting
      evidence that the QPT could be useful in PD assessment of elderly French speaking
      patients.

PMID- 9547129
TI  - Does a teaching programme improve general practitioners' management of depression
      in the elderly?
AB  - General Practitioners have a central role to play in the management of depression
      in their older patients. However, studies suggest that GPs tend to underdiagnose
      and undermanage depression in this age group. Continuing Medical Education is an
      important part of helping GPs keep up to date and improve their practice. We set
      out to see what effect a half a day postgraduate training course had on the views
      and knowledge of a group of local GPs on the management of depression in the
      elderly. Twenty-one general practitioners attended the course and of these
      fifteen completed a questionnaire with clinical vignettes before and six weeks
      after the course. Analysis of the questionnaire and vignette data showed
      significant improvements in a number of areas: in particular, GPs' knowledge
      about antidepressant treatment increased, as did their preference for cognitive
      behavioural therapy out of a range of psychological treatments. This study
      indicates that a teaching package on depression in the elderly can improve
      general practitioner's management knowledge. It also suggests that old age
      psychiatrists can play an important part in the education of their GP colleagues.
      Nevertheless, further studies are needed to ensure that educational programmes
      make an effective impact on the underdiagnosis and undertreatment of depression
      in the elderly.

PMID- 9547130
TI  - Response characteristics to antidepressants and placebo in post-traumatic stress
      disorder.
AB  - Characteristic response patterns are described for two antidepressant drugs and
      placebo in post-traumatic stress disorder. Early onset and steady improvement
      occurred on a global rating scale for both drugs and placebo in those who
      ultimately met responder criteria at the end of treatment. In certain cases, the
      magnitude of global response was greater for drug than for placebo. At weeks 2 or
      4, the Clinical Global Impressions score for fluoxetine but not for
      amitriptyline, served as a good predictor of eventual response. In a review of
      numerous completed placebo-controlled trials, antidepressants were superior to
      placebo in seven out of eight comparisons using the Clinical Global Impressions,
      although specific effects on post-traumatic stress disorder scales were more
      variable. Drug response rates are similar for combat and civilian trauma samples,
      but placebo response rates may be higher in the latter. Effect sizes suggested a
      moderate-to-good effect for drug therapy.

PMID- 9547131
TI  - The dopamine hypothesis of schizophrenia: current status, future prospects.
AB  - The dopamine hypothesis of schizophrenia is reviewed in the context of recent
      advances in dopamine research. These include the following: the discovery that
      there are several subtypes of dopamine receptor, the recognition that the
      activity of dopamine neurons is controlled by negative feedback systems; insights
      into the functions of different subsystems of dopamine neurons; the discovery
      that different subsystems of dopamine neurons interact with one another; and a
      growing understanding of the functions and mode of operation of the forebrain
      regions that the dopamine projections innervate. The paper reviews some of the
      complexities that the dopamine hypothesis has encountered, and continues to
      encounter, with a particular focus on three issues: the adequacy of our
      understanding of neuroleptic drug action, the heterogeneity of schizophrenic
      symptoms and the paucity of direct evidence to support the hypothesis. It is
      concluded that schizophrenia does not reflect primary abnormalities of dopamine
      transmission, but probably does reflect abnormalities in systems that have an
      intimate interaction with the dopamine system. The primary substrates for
      schizophrenia will probably be found within the major targets of the ascending
      dopamine projections: the fronto-striato-pallido-thalamic loops, and the limbic
      structures, such as amygdala and hippocampus, with which the fronto-striatal
      system interacts.

PMID- 9547132
TI  - A 2-year study of sertraline in the treatment of obsessive-compulsive disorder.
AB  - The present study investigated the tolerability, safety profile, and anti
      obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor,
      during long-term treatment of patients with obsessive-compulsive disorder (OCD).
      Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study
      comparing sertraline and placebo subsequently entered a 1-year open extension.
      Among the 51 patients who had been treated with sertraline during the double
      blind phase, the mean total duration of sertraline treatment was 690 days. Only
      treatment responders who completed the 52-week double-blind treatment phase were
      permitted to enter the open extension. The higher rate (p < 0.02) of sertraline
      patients (51 out of 241) than of placebo patients (eight out of 84), who
      responded to treatment and entered the open-label phase is therefore consistent
      with the greater mean improvement observed in the sertraline group during double
      blind treatment. Placebo responders differed from sertraline responders in that
      they were less impaired at baseline of the double-blind study [Yale-Brown
      Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4] and they exhibited less
      improvement during double-blind treatment (-6.1 versus -11.4). In the open-label
      phase all patients received sertraline at a starting dose of 50 mg once a day,
      titrated in 50 mg increments to a maximum dose of 200 mg according to clinical
      response. At end-point the mean Y-BOCS score for all patients decreased by a
      further 3.6 points. Patients previously treated with placebo showed greater
      improvement after being switched to sertraline than those who received continued
      sertraline treatment. Patients who completed the study and received 2 full years
      of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points
      using the Y-BOCS. Sertraline was well tolerated during both the double-blind
      phase and the open extension, and the incidence of adverse experiences was
      generally reduced during the second year of treatment. Three patients
      discontinued open treatment because of adverse experiences. Long-term sertraline
      treatment did not appear to be associated with the emergence, increased
      incidence, or increased severity of adverse experiences or clinically significant
      abnormalities in laboratory tests, vital signs, or the electrocardiogram. The
      study supports the long-term safety and tolerability of sertraline over a 2-year
      treatment course and the sustained efficacy of sertraline in patients with OCD.

PMID- 9547133
TI  - Moclobemide effects on prolactin plasma levels in healthy individuals: the
      hormonal increase induced by a single dose is maintained during a 4-week period
      of drug intake.
AB  - Neuroendocrine challenge studies are frequently used to study the pathophysiology
      of psychiatric illnesses and the effects of psychotropic drug treatment on brain
      monoamine function. Moclobemide, a reversible inhibitor of monoamine oxidase,
      with predominant effects on the A-type of the enzyme, was administered to 15
      healthy men. Seven out of the 15 also received single blind placebo a week before
      the moclobemide. The individuals received moclobemide as a single dose (150 mg),
      followed by doses of 150 mg three times a day, during a 4-week period. Plasma
      prolactin was measured in the morning over a 150-min period, following the single
      dose, and then at the end of weeks 1, 2 and 4 of moclobemide intake. The present
      data show an acute and transitory increase of plasma prolactin levels after the
      single dose, and also during the long-term moclobemide administration. It might
      indicate that steady-state moclobemide levels, during the long-term drug
      administration, were low and thus large fluctuations of drug levels occurred
      between doses. Thus, it is suggested that larger doses or administering smaller
      doses more frequently, or both, may induce hyperprolactinaemia with clinical
      consequences.

PMID- 9547134
TI  - A double-blind multicenter trial comparing sertraline and citalopram in patients
      with major depression treated in general practice.
AB  - The purpose of this double-blind, multicenter trial was to compare the efficacy
      and safety of sertraline (50-150 mg/day) with those of citalopram (20-60 mg/day)
      in patients with major depression in general practice during 24 weeks of
      treatment. The patients were assessed using the Montgomery-Asberg Depression
      Rating Scale and the Clinical Global Impressions of severity and improvement
      scales. Observed and spontaneously reported adverse events were recorded and side
      effects were assessed by means of the UKU Side-Effect Scale. Altogether 400
      patients were randomized into the study. A total of 308 patients completed the 24
      week study in accordance with the protocol. A significant reduction in the total
      Montgomery-Asberg Depression Rating Scale scores was observed in both treatment
      groups as early as 2 weeks, with no statistically significant differences between
      the drugs. In the intention to treat-last observation carried forward analysis
      76% responded to treatment in the sertraline and 81% in the citalopram group. The
      final mean doses were 82 mg/day (64% higher than baseline) in the sertraline
      group and 34 mg/day (70% higher than baseline) in the citalopram group. The
      response rate in completers in accordance with protocol was 90% in the sertraline
      group and 93% in the citalopram group. The side-effects were those usually seen,
      and both sertraline and citalopram were considered to be well tolerated. It was
      concluded that patients with major depression in general practice respond well to
      24 weeks of treatment with sertraline or citalopram. With regard to efficacy, no
      statistically significant differences were found between the drugs.

PMID- 9547135
TI  - Long-term risperidone treatment in bipolar disorder: 6-month follow up.
AB  - Antipsychotic agents, such as clozapine and risperidone, have been reported to be
      beneficial in the treatment of some bipolar patients. Many bipolar patients
      experience 'breakthrough episodes' of mood disorder, with mania or depression
      recurring despite adequate ongoing levels of one or more mood-stabilizing
      medications. There are no controlled studies of breakthrough episodes, and there
      is little open experience to guide clinicians in pharmacotherapy of breakthrough
      episodes. This report describes the outcome of adjunctive risperidone treatment
      in breakthrough episodes of bipolar disorder. We assessed the outcome of openly
      adding risperidone to the medication regimen of 12 outpatients with bipolar
      disorder, type I, who suffered breakthrough episodes despite adequate maintenance
      medication (lithium, valproate, or carbamazepine, or a combination of these).
      Prospective ratings were made at each clinical visit using the Clinical Global
      Impressions and Global Assessment of Functioning scales. Patients received
      risperidone for a mean of 6.0 months (23.96 weeks, range 0.5-72 weeks) at a mean
      dose of 2.75 mg/day (range 1-4.5 mg/day). Four patients discontinued medication
      (two because of lack of efficacy at weeks 6 and 64, and two because of adverse
      events at weeks 0.5 and 23). Among the remaining eight patients, four experienced
      a 10-25 point improvement in Global Assessment of Functioning scores and were
      rated much better on the Clinical Global Impression-Improvement scale. Although
      one patient suffered a major depressive recurrence (at week 22), no patient
      experienced worsening of mania. This small open series suggests a subgroup of
      bipolar patients with breakthrough episodes may benefit from treatment with
      risperidone.

PMID- 9547136
TI  - Serotonin syndrome--clomipramine too soon after moclobemide?

PMID- 9547137
TI  - The ribosomal RNA gene region of Nosema apis (Microspora): DNA sequence for small
      and large subunit rRNA genes and evidence of a large tandem repeat unit size.
AB  - The ribosomal RNA (rRNA) gene region of the microsporidium, Nosema apis, has been
      examined. A new method for extracting microsporidian genomic DNA from infected
      host tissue is described. Complete DNA sequence data are presented for the small
      subunit gene (1242 bp), the internal transcribed space (33 bp), and the large
      subunit gene (2481 bp to a putative termination point). This is the first time
      that the complete large subunit rRNA gene has been published for any
      microsporidian species. DNA sequence is also presented for the regions flanking
      the 5' end of the small subunit gene and the 3' end of the large subunit gene.
      The intergenic spacer is shown to be heterogeneous, showing variation in sequence
      and restriction sites rather than length and containing sequence repeats, which
      are a characteristic feature of intergenic spacers. The rRNA gene region of N.
      apis is shown to occur in a head-to-tail, tandemly repeated manner, as in other
      eukaryotes. This repeat unit is shown to be approximately 18 kb in length. The
      nucleotide sequence presented has been submitted to the Genbank database under
      the accession number U97150.

PMID- 9547138
TI  - Fabrication of a guide for nonradiographic evaluation of bone contour.

PMID- 9547139
TI  - Functional analysis of the cellobiohydrolase I promoter of the filamentous fungus
      Trichoderma reesei.

PMID- 9547140
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 12-1998. A 68-year-old man with a rash, diabetes insipidus, and
      laryngeal stenosis.

PMID- 9547141
TI  - Should all people over the age of 50 have regular fecal occult-blood tests? If it
      works, why not do it?

PMID- 9547142
TI  - The obesity problem.

PMID- 9547143
TI  - The obesity problem.

PMID- 9547144
TI  - The obesity problem.

PMID- 9547145
TI  - The obesity problem.

PMID- 9547146
TI  - The obesity problem.

PMID- 9547147
TI  - The obesity problem.

PMID- 9547148
TI  - The obesity problem.

PMID- 9547149
TI  - Age, body-mass index, and mortality.

PMID- 9547150
TI  - Age, body-mass index, and mortality.

PMID- 9547151
TI  - Age, body-mass index, and mortality.

PMID- 9547152
TI  - Six years' follow-up after hepatitis A vaccination.

PMID- 9547153
TI  - Accidental deep hypothermia.

PMID- 9547154
TI  - Accidental deep hypothermia.

PMID- 9547155
TI  - Accidental deep hypothermia.

PMID- 9547156
TI  - Circulating endothelial cells in sickle cell anemia.

PMID- 9547157
TI  - Circulating endothelial cells in sickle cell anemia.

PMID- 9547158
TI  - Evaluating CME speakers.

PMID- 9547159
TI  - Melatonin induces hyporeactivity caused by type II collagen in peripheral blood
      lymphocytes from patients with autoimmune hearing losses.
AB  - We have studied the behavior of peripheral blood lymphocytes in healthy controls
      and in patients with various hearing losses. These hearing losses were of an
      autoimmune origin in which type II collagen and melatonin were either present or
      absent, activated or not with concanavalin A (Con A). In patients with autoimmune
      hearing losses, the results showed lymphocytes that displayed hyporeactivity to
      type II collagen in terms of their proliferative activity in the presence of Con
      A. The hyporeactivity is specially relevant in those cells which are melatonin
      incubated. When different nosologic entities were studied, we observed similar
      lymphocyte hyporeactivity to type II collagen in bilateral sensorineural hearing
      loss, Meniere's disease and otosclerosis. We conclude that in the lymphocytes of
      patients with autoimmune hearing losses, there is hyporeactivity to type II
      collagen when compared to the hyporeactivity of lymphocytes in control groups.
      This hyporeactivity is revealed when the lymphocytes are activated in the
      presence of melatonin.

PMID- 9547160
TI  - Corticosubthalamic input zones from forelimb representations of the dorsal and
      ventral divisions of the premotor cortex in the macaque monkey: comparison with
      the input zones from the primary motor cortex and the supplementary motor area.
AB  - Employing double anterograde axonal tracing in combination with intracortical
      microstimulation, we examined the distribution patterns of corticosubthalamic
      inputs from forelimb representations of the dorsal (PMd) and ventral (PMv)
      divisions of the premotor cortex in the macaque monkey. The inputs from the PMd
      and PMv were distributed mainly in the medial aspect of the subthalamic nucleus
      (STN), in which their distribution areas overlapped each other. By the same
      experimental approach, we further compared corticosubthalamic input zones from
      the PMd/PMv with those from the primary motor cortex (MI) and the supplementary
      motor area (SMA). The input zones from the PMd/PMv and SMA largely overlapped in
      the medial aspect of the STN, whereas the input zones from the PMd/PMv and MI
      were virtually segregated mediolaterally in the STN.

PMID- 9547161
TI  - Expression of Ly-6C on microglia in the developing and adult mouse brain.
AB  - Expression of Ly-6C, a murine homolog of human CD59, in the brain was examined
      immunologically using an ER-MP20 monoclonal antibody both in vitro and in vivo.
      Ly-6C was expressed both on the isolated microglia and on microglia in the
      developing and adult cerebellum. The number of cerebellar microglia expressing Ly
      6C markedly increased during the first postnatal week in mouse development. The
      expression of Ly-6C on microglia in the developing and adult brain may be related
      to the unique role(s) of microglia under normal and/or pathological conditions of
      the brain.

PMID- 9547162
TI  - Developmental changes in distribution patterns of phencyclidine-induced c-Fos in
      rat forebrain.
AB  - In the forebrain of 56-day-old rats, histochemical studies revealed that the
      subcutaneous injection of a psychotomimetic phencyclidine (PCP; 1 and 10 mg/kg)
      induced a dose-related and dense nuclear c-Fos-like immunoreactivity in the
      pyriform cortex, layers IV-VI of the neocortex and septum, but a sparse c-Fos
      immunostaining in the olfactory tubercle and mid-lateral striatum. Infant rats at
      postnatal day 8 expressed much fewer and more confined c-Fos-positive cells in
      the neocortex than young adult rats following PCP injection. However, a similar
      expression pattern of PCP-induced c-Fos was observed in the pyriform cortex, mid
      lateral striatum, olfactory tubercle and septum between the infant and adult
      periods. These developmental changes in the regional distribution of a neuronal
      activity marker, c-Fos, suggest that neuronal populations involved in PCP-induced
      abnormal behavior are influenced by postnatal development, at least, in the
      neocortex.

PMID- 9547163
TI  - Motor unit discharge rate is not associated with muscle relaxation time in
      sustained submaximal contractions in humans.
AB  - The muscle wisdom hypothesis suggests that motor unit discharge rates decrease in
      parallel with the slowing of muscle contractile properties during fatigue. In
      this study, the discharge rates of single motor units and the muscle contractile
      properties were measured during a sustained submaximal contraction. The majority
      of motor units that were active from the beginning of the task demonstrated a
      decline in discharge rate in the absence of any slowing of muscle relaxation
      time. These findings suggest that the muscle wisdom hypothesis may not apply to
      sustained submaximal contractions.

PMID- 9547164
TI  - Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in
      cerebrospinal fluid of Alzheimer's disease patients.
AB  - We quantitated interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble
      form of the IL-6 signal-transducing protein gp130 (sgp130) in cerebrospinal fluid
      (CSF) of patients with Alzheimer's disease (AD) (n = 17) and control subjects (n
      = 18) using sensitive enzyme-linked immunosorbent assays (ELISA). Our results
      show that none of the parameters examined was significantly different in CSF of
      AD patients as compared to control age-matched non-demented patients. We conclude
      that CSF levels of IL-6 and their soluble receptors do not necessarily reflect
      local changes of the IL-6 system that has been shown to be involved in
      neurodegenerative events occurring in AD. Levels of sgp130 are substantially high
      (approximately 100 ng/ml) in the CSF of all individuals probably representing a
      high antagonistic potential.

PMID- 9547165
TI  - Reduced cholinergic function in normal and Alzheimer's disease brain is
      associated with apolipoprotein E4 genotype.
AB  - Apolipoprotein E (ApoE) is a potent risk factor for Alzheimer's disease. Since
      the loss of cholinergic function in Alzheimer's disease is known to occur at an
      early stage in the disease we have examined this function in normal subjects with
      an Apoepsilon4 allele to see if the deficit occurs in the absence of Alzheimer
      pathology or symptoms. We report that brain tissue obtained post-mortem from
      normal subjects and Alzheimer patients with an Apoepsilon4 allele has a lower
      cholinergic activity than tissue from those subjects without this allele. This
      has important significance for the interpretation of the cholinergic deficits
      found in Alzheimer's disease.

PMID- 9547166
TI  - Nociceptin hyperpolarises neurones in the rat ventromedial hypothalamus.
AB  - Patch-clamp recording techniques were used to examine the effect of nociceptin
      upon neurones contained in slices from the rat ventromedial hypothalamus (VMH).
      Bath application of 50-300 nM nociceptin hyperpolarised neurones in a
      concentration-dependent manner that was not affected by either tetrodotoxin (TTX)
      or naloxone. In voltage-clamp studies nociceptin induced an outward current at 
      60mV that had a reversal potential of -100.2 +/- 4.6 mV and was abolished by bath
      application of 2 mM BaCl2.

PMID- 9547167
TI  - Paired helical filament morphology varies with intracellular location in
      Alzheimer's disease brain.
AB  - Paired helical filaments (PHFs) are one of the hallmark pathologies of
      Alzheimer's disease (AD). PHFs occur in three intracellular locations, although
      hitherto, it was not known whether all PHFs are structurally homogeneous.
      Parietal cortex biopsies were taken from five patients with a clinical and
      histopathological diagnosis of AD and processed for electron microscopy.
      Photomicrographs were then taken of PHFs in neurofibrillary tangles (NFTs),
      neuropil threads (NTs) and neuritic plaque (NP) neurites and their dimensions
      measured. The mean half period, maximum and minimum widths of PHFs in NFTs were
      significantly smaller than those in NTs or NP neurites. The mean half period and
      maximum width of PHFs in NTs were similar to those in NP neurites. These results
      reveal the presence of two distinct PHF populations and investigation of their
      relationship may shed light on the pathogenesis of AD.

PMID- 9547168
TI  - NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's
      disease.
AB  - NACP, originally identified as a precursor of the non-Abeta component of
      Alzheimer's disease amyloid (NAC), is now known to be identical to alpha
      synuclein, a presynaptic protein in the human brain. Recently, a mutation in the
      alpha-synuclein gene in families with autosomal dominant Parkinson's disease (PD)
      was identified. We carried out immunohistochemical examinations of the brains of
      sporadic PD patients using anti-NACP and anti-ubiquitin antibodies. Consistent
      with previous studies, the anti-NACP antibody immunostained the neuropil in a
      punctate pattern throughout the brain. Moreover, much stronger NACP
      immunoreactivity was found in Lewy bodies and degenerating neurites in the
      brainstem. Serial sections immunolabeled with anti-ubiquitin or anti-NACP showed
      that all ubiquitin-immunoreactive LBs were also NACP-immunoreactive. These
      findings suggest that alteration of NACP metabolism is involved in the
      pathogenesis of PD, particularly in Lewy body formation, leading to
      neurodegeneration.

PMID- 9547169
TI  - mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate (NMDA)
      receptor subunit.
AB  - The expression of the N-methyl-D-aspartate (NMDA) receptor subunit NR2B/epsilon2
      (GRIN2B) in the human adult brain was assayed by in situ hybridisation, by using
      a specific cRNA probe. The full length GRIN2B cDNA was cloned and sequenced. It
      showed a 90% nucleotide conservation when compared to the rodent homologue.
      GRIN2B gene is expressed at high levels in the fronto-parieto-temporal cortex and
      hippocampus pyramidal cells and, at a lower extent, in the basal ganglia
      (amygdala and striatum). The cerebellar granule cells does not show any mRNA
      expression. The non-ubiquitous anatomical distribution of the GRIN2B mRNA in the
      central nervous system suggests that the gene could be involved in specific
      functions pertaining to the expressing cell groups.

PMID- 9547170
TI  - Lack of translation of normal 7B2 mRNA levels in hypothalamic mutant vasopressin
      cells of the homozygous Brattleboro rat.
AB  - The homozygous Brattleboro rat (di/di) synthesizes a vasopressin (VP) precursor
      with an aberrant C-terminus, which causes a hypothalamic form of diabetes
      insipidus. The neuroendocrine polypeptide 7B2 is present in VP and oxytocin (OT)
      neurons of the supraoptic and paraventricular nucleus of the hypothalamus in wild
      type rats. However, in the di/di rat 7B2 immunoreactivity is absent in the VP
      cell population, whereas 7B2 levels within the OT cells are unaffected.
      Remarkably, there is no obvious difference in 7B2 transcript levels between VP
      and OT neurons in the di/di rat hypothalamus. This study shows that the presence
      of mRNA does not automatically result in the subsequent synthesis of its protein.
      Cellular mechanisms underlying this discrepancy are discussed.

PMID- 9547171
TI  - Age changes in dopamine levels in the corpus striatum of Albino Swiss (AS) and
      AS/AGU mutant rats.
AB  - The AS/AGU rat is characterised by an ungainly, staggering gait, hind-limb
      rigidity, whole body tremor and (in older animals) difficulty in initiating
      movement. Brains of AS and AS/AGU males aged between 3 and 12 months (n = 10 per
      group) were sectioned transversely on a cryostat (-20 degrees C) to produce two
      successive cut faces (corresponding approximately to Bregma +1.2 and -0.5 mm) and
      1 mm diameter x 1 mm deep micropunches were taken from four areas of the caudate
      putamen. Levels of dopamine in all four areas (measured by HPLC-ECD followed by
      protein estimation) peaked at around 6 months and then declined in AS and AS/AGU
      rats. In the dorsal and lateral caudate-putamen, dopamine levels were
      significantly reduced in AS/AGU rats compared to AS controls from 6 months
      onwards. This provides further evidence that the AS/AGU mutant has impairment of
      its striatal dopaminergic systems.

PMID- 9547172
TI  - Pentylenetetrazol kindling decreases N-methyl-D-aspartate and kainate but
      increases gamma-aminobutyric acid-A receptor binding in discrete rat brain areas.
AB  - Pentylenetetrazol is a convulsive drug acting on gamma-aminobutyric acid-A
      (GABA[A]) gated-chloride receptors. In this study we used a subconvulsive dose
      (30 mg/kg) of pentylenetetrazol to induce a fully kindled state in rats.
      Glutamate receptors were evaluated using [3H]-[1(2-thienylcyclohexyl)]-piperidin
      (TCP) and [3H]kainate receptor autoradiography and [3H]muscimol autoradiography
      was used to study GABA(A) receptors. In fully kindled rats decreased N-methyl-D
      aspartate receptor binding was found in parietal cortex, area CA2 of hippocampus
      and piriform cortex. Decreased kainate receptor binding was observed in all areas
      of the hippocampus, the medial amygdala and in the piriform cortex in the kindled
      rats. In contrast, GABA(A) receptor binding increased in the dentate gyrus. It is
      concluded that modulatory neuronal plasticity events are induced in fully
      pentylenetetrazol kindled rats, which appears to lead to decreased glutamatergic
      excitation and increased GABAergic inhibition in brain regions implicated in the
      development of seizure activity.

PMID- 9547173
TI  - [Bone substitution materials].

PMID- 9547174
TI  - Urine testing--2. urinalysis.

PMID- 9547175
TI  - She can't help it. Fetal alcohol syndrome haunts those who watch but can't change
      things.

PMID- 9547176
TI  - Optical character recognition. Let a scanner spare you those inputting ordeals.

PMID- 9547177
TI  - Monitor chamber backscatter for intensity modulated radiation therapy using
      multileaf collimators.
AB  - Backscattered radiation into the machine monitor chamber can affect the machine
      output variation, with changes in field size and shape. For intensity modulated
      radiation therapy (IMRT) where many field, which may have small dimensions, are
      summed to give an intensity modulated field, the magnitude of backscatter will be
      different due to both the backscattering surface area changing, and the delivered
      monitor units being larger than for the equivalent static field. The effect of
      backscatter variation with field size for a Philips SL15 accelerator has been
      investigated at 8 MV for static and IMRT fields both in the standard clinical
      operating condition where an anti-backscatter plate is fitted, and also for a
      case where the anti-backscatter plate has been removed. The results show that in
      the absence of the anti-backscatter plate the variation in output between a 4 cm
      by 4 cm field and a 40 cm by 40 cm field size due to backscattered radiation was
      5% for static fields. The anti-backscatter plate reduced this variation to less
      than 1%. When the accelerator operated in IMRT mode, with the backscatter plate
      in place, changes in the output due to additional backscattered radiation were
      less than 0.3%. With the backscatter plate removed, the outputs were lower,
      indicating the presence of additional backscattered radiation. It can be
      concluded that for the Philips MLC and SL accelerator with its anti-backscatter
      plate, the effects of backscattered radiation can be ignored for both static and
      IMRT fields.

PMID- 9547178
TI  - [Progress in research on etiopathogenesis of schizophrenia in recent decades].
AB  - In this paper, a progress in research on etiopathogenesis of schizophrenia made
      in the recent decade was presented. Two main etiopathogenetic factors in this
      illness include genetic predisposition and brain damage in early period of life,
      leading to a disorder of brain development and lateralization, and to an
      increased susceptibility to stress. The use of new methods of genetic studies
      brought about a significant progress as to identification of relationship between
      schizophrenia and various changes within genotype. In the 1990s, many data have
      been obtained concerning possible brain damaging factors as well as the existence
      of structural and functional brain abnormalities in this illness. Impaired brain
      development in schizophrenia results in disturbances of neuronal connection in
      the cortical structures and in cortical-limbic transmission, what may underlie
      the appearance of psychopathological symptoms. New neuroleptic drugs introduced
      in the recent years show more complete therapeutic action against schizophrenic
      symptoms compared with drugs used so far. This may result from their broader
      influence on the pathogenetic processes of schizophrenia, which may be due, apart
      from their effect on dopaminergic system, also to their action on some elements
      of serotonergic neurotransmission.

PMID- 9547179
TI  - [Neurodevelopmental schizophrenia: the concept of developmental origins of
      certain forms of schizophrenia].
AB  - This article presents the concept of neurodevelopmental schizophrenia and reviews
      the studies that contributed to its formulation. According to this concept some
      forms of schizophrenia (early onset, with predominating negative symptoms) are
      conditioned by distorted CNS development, probably in prenatal period. Such
      pathogenesis of certain forms of the disease is suggested by the following
      results of the studies on the CNS structure and function in schizophrenia: 1)
      structural abnormalities on in vivo brain imaging and postmortem studies 2)
      cytoarchitectural distortions in some brain regions, suggestive of disruption of
      cell migration during the CNS developmental processes 3) co-occurrence of the CNS
      congenital anomalies, minor physical anomalies and schizophrenia 4) neurological
      defects and psychosocial childhood dysfunction in individuals with adult onset
      schizophrenia. Genetical conditions, viral infections in prenatal period,
      obstetric complications or combination of the mentioned factors are considered as
      the factors disturbing the CNS developmental processes.

PMID- 9547180
TI  - [Structural brain changes in the computerized tomography of schizophrenic
      patients].
AB  - VBR was higher and the cortical atrophy more frequent in the schizophrenic
      patients as compared to the control group. VBR correlated negatively with SANS
      and PANSS (negative) scores, especially with alogia and inattention, it also
      correlated positively with female sex. Positive intercorrelations were found
      between VBR and other ratios concerning lateral ventricles and no correlations
      were found between them and cortical atrophy.

PMID- 9547182
TI  - [Social functioning of schizophrenic patients after 15 years from the first
      hospitalization (Part I -- evaluation of social functioning)].
AB  - Catamnestic data concerning 109 patients, inhabitants of Warsaw-Praga,
      hospitalized for the first time in the years 1978-79 with schizophrenia (92
      persons) or paranoid psychosis-ICD IX number 297.9 (17 persons), were collected
      in 1993-94. Smaller number and shorter duration of hospitalisations has been
      observed during 15 years, in comparison with other Polish data. Twenty persons
      died during the period of observation. In the group of 85 investigated persons
      69% were not working at all-15% were fully and 18% partially unable to meet their
      basic needs on their own-29% were temporarily or permanently unable to function
      adequately in their marital and/or parental roles, 31% were single and childless.
      Taking into account the mortality among 109 observed persons (18.7% during 15
      years); good prognosis according to social functioning has been found in 48.6% of
      the group observed at first hospitalisation.

PMID- 9547181
TI  - [Cortical atrophy in MRI, mental status and neuroleptic treatment effect in
      schizophrenia].
AB  - MR imaging of the head was performed in forty schizophrenics (DSM-IV). Mental
      status was evaluated before and during 8-weeks of neuroleptic treatment. Cortical
      atrophy in frontal and temporal regions was found in 40% of subjects. They were
      older, had longer history of schizophrenia, were less active professionally and
      were more frequently hospitalized. Patients with and without cortical atrophy in
      MRI did not differ in the severity of schizophrenic psychopathology at baseline.
      During neuroleptic treatment negative schizophrenia symptoms were significantly
      better diminished in patients without cortical atrophy than in subjects with
      cortical atrophy in MRI; this regarded specially the severity of emotional
      blunting. Clinical improvement after 8-weeks of neuroleptic administration was
      less favorable in patients with cortical atrophy.

PMID- 9547183
TI  - [Social functioning of schizophrenic patients after 15 years from the first
      hospitalization (Part II -- the evaluation of needs for community care)].
AB  - The description of the studied group was given in the first part of the paper.
      Some of the factors having been present at the first hospitalization were found
      to be important for the patients' functioning 15 years later. On the basis of the
      collected regarding data 85 patients, significant coincidence has been found
      between more intensive use of extramural services, more frequent and longer
      hospitalizations, and worse social functioning during 15 years' period in
      individual cases. The conclusion has been assumed that there exists obvious need
      for more intensive community care for such patients. On the basis of 0.15%
      morbidity index the number of schizophrenics needing social support, sheltered
      accommodation and sheltered working conditions were estimated. According to the
      Mental Health Care Act of 1994 such services have to be organized within social
      care system.

PMID- 9547185
TI  - [Psychoeducation in schizophrenia relapse prevention].
AB  - Schizophrenia is a chronic disease, with phase course. Most of patients (about
      78%) experience more than one episode of the disease in the course of life.
      Pharmacotherapy is the standard method of troating schizophrenia. Since the
      middle of the 70 a new orientation of therapy of schizophrenia has been
      developing. Its main goal is prophylaxis, which combines pharmacotherapy and
      psychosocial treatment. In the paper we discuss the term "relapse of
      schizophrenia" and researches concerning the index of relapses and dynamics of
      the disease. We present theoretical presumptions which are the base of
      psychoeducational programs, that is, stress-vulnerability model. The main
      purposes of psychoeducation in schizophrenia are also discussed. The article
      contains current review of the researches relative to effectiveness of
      psychoeducational programs in relapse of schizophrenia prevention.

PMID- 9547184
TI  - [Comparison of quality of life of schizophrenic patients in different forms of
      psychiatric care].
AB  - Health related quality of life and severity of psychopathological symptoms were
      evaluated in 90 patients with schizophrenia, hospitalized in a psychiatric ward
      in a day hospital or followed by the therapist in a community care center. No
      statistical differences were found in the quality of life evaluation between
      patients from all three settings. The quality of life did not correlate with the
      severity of schizophrenic symptoms. Older patients and those more frequently
      hospitalized were more pessimistic in evaluation of their quality of life. Health
      status transition, as compared to the situation one year before, correlated
      inversely with patients' age. Male patients as well as patients from
      schizophrenic families evaluated their quality of life as worse.

PMID- 9547186
TI  - [Negative symptoms with relation to the remission in the early stage of
      schizophrenic psychosis].
AB  - 103 patients were admitted for the first time to the psychiatric hospital
      (Institute of Psychiatry and Neurology in Warsaw) between 1976-1983 and received
      a research diagnosis of schizophrenia (in accordance with the ICD-9 criteria).
      The course and clinical pattern of the illness were analyzed at a follow-up in 65
      patients-rehospitalized in the 5th year from their first admission and in 10
      patients not rehospitalized during catamnestic period. As regards the clinical
      pattern analysis, it was focussed on negative symptoms occurrence, as assessed
      using the Andreasen Scales (SANS). The quality of remission was evaluated. The
      data obtained from the case reports were statistically tested and the results
      were presented in the tables according to the research questions. The occurrence
      of negative symptoms (affective blunting, alogia, apathy, anhedonia, attention)
      at first hospitalization had no relation to the quality of the remission at the
      five-year follow-up.

PMID- 9547187
TI  - [Follow-up studies of psychotic patients receiving inpatient treatment or
      alternative forms of psychiatric care].
AB  - An analysis of populations treated in the III Department of Psychiatry indicates
      that 12 years since the transformation of the organizational model of care for
      patients from sub-regionalized catchment area, inpatient treatment continues to
      be of major importance, as it was provided to over half of all referrals.
      Intermediate forms of care, replacing a half of the former number of psychiatric
      beds, were offered mainly to schizophrenic patients, with the exclusion of those
      with a marked agitation, psychomotor retardation, or aggressive, presenting
      imminent danger to self or others. At one-year follow-up J.E. Overall's scale was
      used to examine 39 schizophrenic patients treated at the inpatient ward, day
      hospital, or by a community treatment team. Patients treated at the day hospital
      providing an intense therapeutic program manifested a significantly more marked
      improvement in respect of 6 symptoms: autism, affective bluntness, guilt
      feelings, tension, suspiciousness, and bizarre thoughts. No significant
      differences were found between the compared forms of care as regards the degree
      of other symptoms amelioration. Thus, the day hospital turned out to be a more
      effective form of care in case of schizophrenic patients manifesting the cluster
      of symptoms listed above.

PMID- 9547188
TI  - [Family burden of patients receiving inpatient treatment or alternative forms of
      psychiatric care].
AB  - Professionals working with chronic patients are usually aware of vast deficitis
      in what is called in the literature "natural support networks". The deficits
      generally increase over time, as is the case with broadly defined social skills.
      Although the efficacy of biological treatment was similar in all the three forms
      of care, nevertheless, patients and their families, when left without
      psychotherapeutic support provided to them by the day hospital or community
      treatment team, at one-year follow-up indicated lack of any satisfactory
      improvement in many dimensions of their functioning, and in some aspects-even a
      progressive deterioration.

PMID- 9547189
TI  - [Foreign bodies in trachea and bronchi].

PMID- 9547190
TI  - [Non-small cell bronchopulmonary carcinoma. In search of a precise prognosis].

PMID- 9547191
TI  - [Hypertriglyceridemia and plasma insulin in combined familial hyperlipidemia].
AB  - Changes in insulin secretion were investigated in a group of non obese subjects
      with combined familial hyperlipidemia (CFH), with normal glucose tolerance,
      relating the observed changes with plasma triglycerides and lipoprotein
      phenotype. MATERIALS AND METHODS: The study was conducted with 21 subjects (16
      males and 5 females; mean age: 45.9 +/- 9.1 years), diagnosed of CFH after the
      clinical and analytical study of patients and their first degree relatives (9
      with phenotype IIa, 8 IIb, and 4 IV) and 21 healthy control subjects, of similar
      age, sex and body weight. In both groups, lipids, plasma lipoproteins, glucose,
      basal plasma insulin, and insulin after and oral glucose overload (OGO) were
      quantitated. RESULTS: Diastolic blood pressure was higher (p < 0.01) in CFH group
      compared with controls (means: 132/80 vs 123/71 mmHg, respectively). TC, TG and
      Apo B were also higher in the CFH group. With OGO significantly higher serum
      insulin levels were observed at 0, 30, 60, 90 and 120 minutes in CFH subjects
      compared with control group. Basal serum insulin and the area under the curve of
      insulin secretion after OGO was higher in subjects with triglycerides (45,579 +/-
      13,056 in controls, 61,385 +/- 22,254 in CFH IIa, 70,645 +/- 17,271 IIb and
      124,884 +/- 36,944 in CFH IV. Insulin secretion correlated significantly (p <
      0.01) with plasma triglycerides. As conclusion, hyperinsulinism is a finding in
      CFH non obese subjects and with normal glucose tolerance, and has an increasing
      frequency in subjects with high triglycerides levels.

PMID- 9547192
TI  - [Percutaneous implant of Hickman catheters and reservoirs. Long-term experience].
AB  - OBJECTIVE: To report our experience with long term external catheters and
      implantable ports in the last 8 years. MATERIAL AND METHODS: From December 1987
      to August 1995 a total of 617 central venous catheters were implanted in 541
      patients in our Interventionist Vascular Radiology Unit, 265 men (49%) and 276
      women (51%), with a mean age of 46 years. A total of 335 (54%) were partially
      implantable external catheters and 241 (39%) implantable ports in chest and 41
      (7%) in the forearm. RESULTS: A technical success--defined as the possibility of
      implanting the catheter--was achieved in 98% of cases. Immediate complications
      included 5 pneumothorax (0.8%), 11 accidental carotid artery puncture (2%) with
      no clinical relevance, 18 catheter misplacement (3%), and 8 vein spasm (1%).
      Fifty-two catheters (8%) were removed on account of infectious complications.
      Currently, 71 catheters are still in use (12%), 433 (70%) have been removed or
      the catheter was patent until patients's death. CONCLUSIONS: Partially
      implantable central venous catheters and totally implantable ports are a safe
      alternative in patients requiring a central venous access for prolonged
      treatments. The low number of immediate complications renders the Interventionist
      Vascular Radiology Unit the proper place where to perform these procedures.

PMID- 9547193
TI  - [Medical rhabdomyolysis in the elderly].
AB  - BACKGROUND: To investigate the characteristics of medical rhabdomyolysis (RM) in
      the elderly, as well as differences compared with those observed in younger
      patients. PATIENTS AND METHODS: Prospective study of 56 elderly patients (> or =
      65 years) with RM and 73 younger patients (> 7 years and < 65 years) with RM for
      43 months. The RM characteristics were analyzed in the elderly group (ERM) and
      compared with those in the younger group (YRM). RESULTS: Fifty-six elderly
      patients with RM (38 males and 18 females, with a mean age of 76.3 +/- 7.6 years;
      range: 65-92 years) and 73 younger patients (57 males and 16 females, with a mean
      age of 37.9 +/- 15.6 years; range: 13-63 years), made up the 129 patients in the
      study. The most common cause for RM in the ERM was muscle compression due to
      immobilization and the multicausative group, both with 9 (16%) cases, followed by
      respiratory infection with 8 (14.2%) cases. In the YRM, the most common cause was
      physical exertion with 15 patients (20.5%) and multicausative with 18 patients
      (24.6%). Myalgia predominated in the YRM group, with 25 vs. 9 (odds ratio [OR]:
      2.7; 95% confidence interval [CI]: 1.0-7.3; p < 0.05). Acute renal failure (ARF)
      occurred in 13 patients in the ERM group compared with 4 in the YRM group (OR:
      5.2; 95% CI: 1.4-23; p < 0.01). In the logistic regression analysis an
      association was found between hypoalbuminemia and ARF for the ERM group. In the
      presence of ARF, both ERM and YRM had decreased serum calcium levels, deeper in
      YRM and more prolonged in the ERM. Six patients in the ERM died, and four of them
      had developed ARF. In contrast, none of the two deceased patients in the YRM had
      the complication of ARF. CONCLUSION: Almost half of cases of RM occur in elderly
      patients, which is mostly due to muscle compression and infections, particularly
      in the respiratory tract. Symptoms are usually mild and the development of ARF is
      more common than in younger patients, and its presence is associated with
      hypoalbuminemia. Hypocalcemia associated with ARF was less deep in the elderly,
      but more persistent than in younger patients. Most deceased patients in the
      elderly group previously developed ARF.

PMID- 9547194
TI  - [Treatment of Hodgkin's disease with bulky mediastinal involvement. Study of 28
      cases].
AB  - BACKGROUND: Bulky mediastinal involvement in Hodgkin disease (HD) is usually
      considered an adverse prognostic factor. Patients treated with radiotherapy alone
      (RT) or chemotherapy alone (CT) have a high relapse rate. The combined
      chemotherapy plus radiotherapy is the therapy of choice. The objective of the
      present study was to report our results and complications in the treatment of 28
      patients with HD with bulky mediastinal involvement. MATERIALS AND METHODS: A
      retrospective analysis was made of a series of 28 patients with bulky mediastinal
      disease treated in our hospital from 1973-1993, with RT, CT or combined therapy.
      The overall survival rate and free of disease, the presence of residual mass, as
      well as therapy toxicity were studied. RESULTS: The overall remission rate was
      85.7%. The overall survival rates and free of disease were 76% and 78% at 19
      years. Five patients died due to progression of disease, and one due to pulmonary
      toxicity. Neither heart disease nor secondary neoplasms were documented.
      CONCLUSION: Our results, in agreement with those reported in literature, support
      the combined therapy, chemotherapy plus radiotherapy, as the therapy of choice
      for patients with HD and bulky mediastinal involvement.

PMID- 9547195
TI  - [Circadian rhythm and lacunar syndromes].
AB  - BACKGROUND: There is scarce knowledge on the mode of onset of disease related to
      circadian rhythm in lacunar syndromes. METHODS: A prospective clinical analysis
      was conducted in 181 patients with lacunar infarcts (LI) and 47 patients with
      lacunar syndromes not due to lacunar infarcts. In every patient the onset of the
      disease was recorded for each of the four 6-hour equal periods of the day. The
      injure volume of the LI was measured by means of a computer and image analyzer. A
      descriptive analysis of the hour of onset of the disease and a comparative
      analysis of clinical differences and injure size for each day period, relating to
      circadian rhythm were made. RESULTS: For LI, the onset occurred during nocturnal
      sleep in 32.5% and during wakening hours in 67.5%. The morning onset of the
      disease was significantly more frequent in lacunar syndromes by cerebral
      hemorrhage (55.5%) than in LI (24.5%) (p < 0.001). For LI, the mean injure volume
      was significantly larger when associated with a morning onset (2,574 mm3), during
      the afternoon (1,678 mm3) or during the night (1,328 mm3) (p < 0.04). At
      discharge, no significant differences were documented between hospital stay
      length and also between functional disability, when compared with disease onset
      and circadian rhythm. CONCLUSIONS: A third of patients with LI had their onset of
      symptoms during nocturnal sleep. The morning onset of the disease regarding
      circadian rhythm in LI is associated with a larger injure volume.

PMID- 9547196
TI  - [Maternal mortality in Spain, 1980-1992. Relationship with birth distributions
      according to the mother's age].
AB  - The maternal mortality evolution in Spain during the 1980-1992 period is
      reported. The influence of birth distribution according to maternal age is
      analyzed. The information was gathered from vital statistics published by
      Instituto Nacional de Estadistica. The mortality rates have stabilized since 1985
      (4.8 per 10(5) for 1992) associated with the increase in the proportion of births
      in women aged > or = 30 years (40.6% for 1992). Birth distributions according to
      maternal age account for 13.1% of the deaths observed. The predictions point to
      an increase in maternal mortality for the year 2000.

PMID- 9547197
TI  - [Back pain, intervertebral calcifications, and pubic osteitis].

PMID- 9547198
TI  - [Tumor in the left iliac fossa].

PMID- 9547199
TI  - [Obstructive pneumonia in a former smoker].

PMID- 9547200
TI  - [Assessment of operativity in bronchogenic carcinoma surgery].

PMID- 9547202
TI  - [Size decrease as a factor associated with reduction of sensitivity to insulin in
      normoglycemic progeny of patients with non-insulin dependent diabetes mellitus].

PMID- 9547201
TI  - [Indications for combined treatment in Hodgkin's disease. Review of the
      literature].

PMID- 9547203
TI  - [Bilateral myelomatous pleural effusion].

PMID- 9547204
TI  - [Treatment of erythromelalgia with buprenorphine].

PMID- 9547205
TI  - [Hypopotassemia caused by cloxacillin: a new case].

PMID- 9547206
TI  - [Bronchial stenosis secondary to aspiration of a ferrous sulfate tablet].

PMID- 9547207
TI  - [Jan Bedrna. 16 August 1897, Cesky Brod--25 August 1956, Podebrady].

PMID- 9547208
TI  - [P. K. Anokhin: his physiological, general biological and philosophical ideas (on
      the centenary of his birth)].

PMID- 9547209
TI  - [An epidemic outbreak of an acute intestinal infection in a children's center].

PMID- 9547210
TI  - [The centenary anniversary of the Merieux Institute].

PMID- 9547212
TI  - [Psychiatric disorders and cognitive deterioration in Friedreich ataxia].
AB  - The present study was designed with the aim of examining the presence of
      psychiatric diagnosis and intellectual impairment in a sample of patients with
      Friedreich's ataxia. A consecutive sample of 21 patients presenting with
      Friedreich's Ataxia were evaluated by means of a neuropsychiatric interview. Only
      one patient was diagnosed as mentally retarded. Out of the 15 patients of the
      sample who were evaluated with be WAIS, all of them fell within a normal
      intellectual range. The idea that Friedreich's Ataxia produces cognitive
      impairment and serious psychiatric symptoms came from the earliest descriptions
      of the disease at the beginning of this century, which probably included many
      patients in their samples who had other diseases.

PMID- 9547211
TI  - ["Nervous breakdown": a diagnostic characterization study].
AB  - An evaluation was made of the influence of different psychiatric co-morbidities
      on the symptoms of the disorder popularly known as "ataque de nervios" (nervous
      breakdown) among the US Hispanic population. Using a self-completed instrument
      designed specially for both traditional nervous breakdown and for panic symptoms,
      and structured or semi-structured psychiatric interviews for Axis I disorders,
      and evaluation was made of Hispanic subjects who sought treatment for anxiety in
      a clinic (n = 156). This study centered on 102 subjects who presented symptoms of
      "nervous breakdown" and comorbidity with panic disorder, other anxiety disorders,
      or affective disorder. Variations in co-morbidity with "nervous breakdown"
      enabled the identification of different patterns of "nervous breakdown"
      presenting symptoms. Individuals with "nervous breakdown" and panic disorder
      characteristically expressed a greater sense of asphyxiation, fear of dying, and
      growing fear (panic-like) during their breakdowns. Subjects with "nervous
      breakdown" and affective disorder had a greater sensation of anger and more
      tendency toward screaming and aggressive behavior such as breaking things during
      the breakdown (emotional anger). Finally, subjects with "nervous breakdown" and
      co-morbidity with another anxiety disorder had fewer "paniclike" or "emotional
      anger" symptoms. These findings suggest that: a) the widely used term "nervous
      breakdown" is a popular label for different patterns of loss of emotional
      control; b) the type of loss of emotional control is influenced by the associated
      psychiatric disorder; and c) the symptoms characteristics of the "nervous
      breakdown" can be useful clinical markers for associated psychiatric disorders.
      Future research is needed to determine whether the known Hispanic entity "ataque
      de nervios" is simply a popular description for different aspects of well-known
      psychiatric disorders, or if it reflects specific demographic, environmental,
      personality and/or clinical characteristics of the population.

PMID- 9547213
TI  - [Positive and negative symptoms in schizophrenia: standards of change during
      acute exacerbation].
AB  - INTRODUCTION AND OBJECTIVES: The temporal stability of the positive and negative
      symptoms in schizophrenia deserves a special interest due to its consequences in
      the outcome and the treatment of the disease. This study determines the temporal
      stability of positive/negative subtypes in schizophrenia during the acute phase.
      MATERIAL AND METHODS: This is a clinical, observational and prospective study of
      a dynamic cohort of patients with acute exacerbation of schizophrenia defined by
      DSM III-R criteria. Patients with severe and unstable organic pathology,
      substance dependence, mental organic disorder, mental retardation, depression, or
      medicamentous parkinsonism were excluded. Clinical assessment was performed with
      the PANSS scale. Schizophrenic subtypes were established according to inclusive
      and restrictive criteria of PANSS. All patients were treated with new
      antipsycotics and biperiden if necessary. RESULTS: 51 patients were assessed for
      8 weeks. In the baseline, the negative subtype (63.3% and 52.5% by inclusive and
      restrictive system respectively) and paranoid form (45.1%) were predominant.
      Three types of analysis were performed to determine the temporal stability: 1.
      Concordance (Kappa index). The concordance of the inclusive and restrictive
      System, regarding to the baseline assessment, indicated that both criteria had a
      low temporal stability. 2. Mc Nemar Ji Square. This test showed that these
      changes were bi-directional except for the first visit, which was significant
      through the restrictive system (higher change from the negative to other
      subtypes). 3. Transition analysis among groups by First Order Morkov Chains
      analysis indicated that this change was stationary (the change was the same in
      all phases). CONCLUSIONS: 1o The variable "time" has to be considered for the
      definition of subtypes in schizophrenia. 2o The restrictive system is more
      specific. It allows to identify a subgroup of patients with "Negative"
      schizophrenia with a high specificity and validity in clinical and
      epidemiological studies. 3o The use of the baseline visit as a reference (gold
      standard) is recommended because it exits a higher concordance among criteria and
      a more florid psychopathology.

PMID- 9547214
TI  - [Neuropsychological deficits, obstetric complications and premorbid adjustment in
      patients with the first psychotic episode].
AB  - In spite of the great number of studies that have proved the existence of
      cognitive disturbances in schizophrenic subjects, conflicting results have not
      allowed to glimpse a typical pattern of neuropsychological deficits in
      schizophrenia. On the contrary, these results have raised important controversies
      regarding the nature of such cognitive impairment. Thus, questions concerning the
      existence of generalized versus focal cognitive impairment or in relation lo the
      static versus progressive nature of these deficits remain unresolved. In the
      middle of these debates, the need for prospective research, which focuses on the
      neuropsychological deficits of schizophrenia and other psychotic disorders from
      the beginning of the illness, has been pointed out. In these lines we present the
      results obtained in our study in which 59 subjects, who were admitted in our
      hospital for presenting a first psychotic episode, were assessed. Measures of
      premorbid adjustment, obstetric complications and clinical symptoms were taken
      and correlated to measures of cognitive performance obtained by using a
      minibattery of neuropsychological tests at time of dismissal. Results showed, as
      in previous research, that neuropsychological deficits are already present in
      psychotic patients at the beginning of the illness. These deficits in our sample
      were related lo obstetric complications especially in males, and disturbances of
      premorbid adjustment occurred in early stages of development. These results
      support the neurodevelopmental hypothesis of schizophrenia.

PMID- 9547215
TI  - [Descriptive epidemiology of suicide in Spain (1906-1990)].
AB  - INTRODUCTION: In Spain, suicide as a cause of death is increasing in different
      age groups in both sexes. The aim of the present work is to characterize the
      phenomenon of suicide. MATERIALS AND METHODS: A retrospective descriptive
      epidemiological study was carried out. Data periodically published by the
      National Institute of Statistics (INE) on the statistical Incidence of Suicides
      in Spain (1906-1990) were analyzed, processed and tabulated. RESULTS: Suicide
      increases with age and this increase is more pronounced as from 40 years of age.
      The ratio between sexes is 3:1 in favour of men, although with a tendency to
      decrease. The most important causes of suicide are: physical suffering (27%),
      psychopathy (18%) and Daily Activities (DA) (17.5%). The method most used is
      hanging, which has been the case of 37% of the suicides committed in Spain during
      the study period (1906-1990). CONCLUSIONS: The risk factors associated with
      suicide are age, male sex, and physical and mental suffering.

PMID- 9547217
TI  - Errata: Analysis of semen constantly changing social context of medicine.

PMID- 9547216
TI  - [Delirium in delusions of negations of Cotard: syndrome versus disorder].
AB  - This article constitutes the first of a series directed to review fundamental
      disorders in clinical psychogeriatrics. This sort of publication is intended to
      retrieve clinical practice as the cornerstone for research and teaching in
      psychiatry. Besides, and particularly in geriatry, we try to expand the strategy
      of liaison work with primary physicians. In this case, a nosological review of
      the so called "delusion of negations" is presented. The Jules Cotard's original
      concept of subtype of delusional melancholia is contrasted to the view of
      numerous authors in this century who have described it as a form of non-specific
      delusional syndrome.

PMID- 9547218
TI  - In vitro and in vivo regulation of assimilatory nitrite reductase from Candida
      utilis.

PMID- 9547219
TI  - The experience of schizophrenia.

PMID- 9547220
TI  - Disruption of mitochondrial respiration inhibits volume-regulated anion channels
      and provokes neuronal cell swelling.
AB  - Hypoxia and inhibitors of mitochondrial respiration impair the regulatory volume
      decrease (RVD) of cerebellar granule neurons after hypotonic swelling. RVD is
      linked to the opening of volume-regulated anion channels (VRACs). VRACs are
      outwardly rectifying, inactivate slowly during maintained depolarization, and are
      permeable to the cellular organic osmolyte taurine. Channel activation requires
      nonhydrolytic ATP binding and is not modulated by intracellular ADP. VRAC opening
      is reversibly depressed by hypoxia and by mitochondrial inhibitors such as
      oligomycin, rotenone, and antimycin A. These results demonstrate that neuronal
      VRAC activation and swelling are both tightly linked to cellular energy.
      Moreover, the findings reported in this work may have a particular significance
      for inherited mitochondrial human diseases, such as mitochondrial myopathy,
      encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), which cause
      brain swelling and edema.

PMID- 9547221
TI  - Somatodendritic depolarization-activated potassium currents in rat neostriatal
      cholinergic interneurons are predominantly of the A type and attributable to
      coexpression of Kv4.2 and Kv4.1 subunits.
AB  - Unlike other neostriatal neurons, cholinergic interneurons exhibit spontaneous,
      low-frequency, repetitive firing. To gain an understanding of the K+ channels
      regulating this behavior, acutely isolated adult rat cholinergic interneurons
      were studied using whole-cell voltage-clamp and single-cell reverse transcription
      PCR techniques. Cholinergic interneurons were identified by the presence of
      choline acetyltransferase (ChAT) mRNA. Depolarization-activated potassium
      currents in cholinergic interneurons were dominated by a rapidly inactivating, K+
      selective A current that became active at subthreshold potentials. Depolarizing
      prepulses inactivated this component of the current, leaving a delayed, rectifier
      like current. Micromolar concentrations of Cd2+ dramatically shifted the voltage
      dependence of the A current without significantly affecting the delayed
      rectifier. The A-channel antagonist 4-aminopyridine (4-AP) produced a voltage
      dependent block (IC50, approximately 1 mM) with a prominent crossover at
      millimolar concentrations. On the other hand, TEA preferentially blocked the
      sustained current component at concentrations <10 mM. Single-cell mRNA profiling
      of subunits known to give rise to rapidly inactivating K+ currents revealed the
      coexpression of Kv4.1, Kv4.2, and Kv1.4 mRNAs but low or undetectable levels of
      Kv4.3 and Kv3.4 mRNAs. Kv1.1, beta1, and beta2 subunit mRNAs, but not beta3, were
      also commonly detected. The inactivation recovery kinetics of the A-type current
      were found to match those of Kv4.2 and 4.1 channels and not those of Kv1.4 or
      Kv1. 1 and beta1 channels. Immunocytochemical analysis confirmed the presence of
      Kv4.2 but not Kv1.4 subunits in the somatodendritic membrane of ChAT
      immunoreactive neurons. These results argue that the depolarization-activated
      somatodendritic K+ currents in cholinergic interneurons are dominated by Kv4.2-
      and Kv4. 1-containing channels. The properties of these channels are consistent
      with their playing a prominent role in governing the slow, repetitive discharge
      of interneurons seen in vivo.

PMID- 9547222
TI  - G-Protein-coupled modulation of presynaptic calcium currents and transmitter
      release by a GABAB receptor.
AB  - Presynaptic GABAB receptors play a regulatory role in central synaptic
      transmission. To elucidate their underlying mechanism of action, we have made
      whole-cell recordings of calcium and potassium currents from a giant presynaptic
      terminal, the calyx of Held, and EPSCs from its postsynaptic target in the medial
      nucleus of the trapezoid body of rat brainstem slices. The GABAB receptor agonist
      baclofen suppressed EPSCs and presynaptic calcium currents but had no effect on
      voltage-dependent potassium currents. The calcium current-EPSC relationship
      measured during baclofen application was similar to that observed on reducing
      [Ca2+]o, suggesting that the presynaptic inhibition generated by baclofen is
      caused largely by the suppression of presynaptic calcium influx. Presynaptic
      loading of the GDP analog guanosine-5'-O-(2-thiodiphosphate) (GDPbetaS) abolished
      the effect of baclofen on both presynaptic calcium currents and EPSCs. The
      nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)
      suppressed presynaptic calcium currents and occluded the effect of baclofen on
      presynaptic calcium currents and EPSCs. Photoactivation of GTPgammaS induced an
      inward rectifying potassium current at the calyx of Held, whereas baclofen had no
      such effect. We conclude that presynaptic GABAB receptors suppress transmitter
      release through G-protein-coupled inhibition of calcium currents.

PMID- 9547223
TI  - Calcium-dependent regulation of rab3 in short-term plasticity.
AB  - The Rab3 proteins are monomeric GTP-binding proteins associated with secretory
      vesicles. In their active GTP-bound state, Rab3 proteins are involved in the
      regulation of hormone secretion and neurotransmitter release. This action is
      thought to involve specific effectors, including two Ca2+-binding proteins,
      Rabphilin and Rim. Rab3 acts late in the exocytotic process, in a cell domain in
      which the intracellular Ca2+ concentration is susceptible to rapid changes.
      Therefore, we examined the possible Ca2+-dependency of the regulatory action of
      GTP-bound Rab3 and wild-type Rab3 on neuroexocytosis at identified cholinergic
      synapses in Aplysia californica. The effects of recombinant GTPase-deficient
      Aplysia-Rab3 (apRab3-Q80L) or wild-type apRab3 were studied on evoked
      acetylcholine release. Intraneuronal application of apRab3-Q80L in identified
      neurons of the buccal ganglion of Aplysia led to inhibition of neurotransmission;
      wild-type apRab3 was less effective. Intracellular chelation of Ca2+ ions by EGTA
      greatly potentiated the inhibitory action of apRab3-Q80L. Train and paired-pulse
      facilitation, two Ca2+-dependent forms of short-term plasticity induced by a rise
      in intraterminal Ca2+ concentration, were increased after injection of apRab3
      Q80L. This result suggests that the inhibition exerted by GTP-bound Rab3 on
      neuroexocytosis is reduced during transient augmentations of intracellular Ca2+
      concentration. Therefore, a Ca2+-dependent modulation of GTP-bound Rab3 function
      may contribute to short-term plasticity.

PMID- 9547224
TI  - Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural
      constraints, uptake, and receptor activation.
AB  - Fast excitatory synapses are generally thought to act as private communication
      channels between presynaptic and postsynaptic neurons. Some recent findings,
      however, suggest that glutamate may diffuse out of the synaptic cleft and bind to
      several subtypes of receptors, either in the perisynaptic membrane or at
      neighboring synapses. It is not known whether activation of these receptors can
      occur in response to the release of a single vesicle of glutamate. Here we
      estimate the spatiotemporal profile of glutamate in the extrasynaptic space after
      vesicle exocytosis, guided by detailed ultrastructural measurements of the CA1
      neuropil in the adult rat. We argue that the vicinity of the synapse can be
      treated as an isotropic porous medium, in which diffusion is determined by the
      extracellular volume fraction and the tortuosity factor, and develop novel
      stereological methods to estimate these parameters. We also estimate the spatial
      separation between synapses, to ask whether glutamate released at one synapse can
      activate NMDA and other high-affinity receptors at a neighboring synapse. Kinetic
      simulations of extrasynaptic glutamate uptake show that transporters rapidly
      reduce the free concentration of transmitter. Exocytosis of a single vesicle is,
      however, sufficient to bind to high-affinity receptors situated in the immediate
      perisynaptic space. The distance separating a typical synapse from its nearest
      neighbor is approximately 465 nm. Whether glutamate can reach a sufficient
      concentration to activate NMDA receptors at this distance depends critically on
      the diffusion coefficient in the extracellular space. If diffusion is much slower
      than in free aqueous solution, NMDA receptors could mediate crosstalk between
      neighboring synapses.

PMID- 9547225
TI  - Reversal of age-related alterations in synaptic plasticity by blockade of L-type
      Ca2+ channels.
AB  - The role of L-type Ca2+ channels in the induction of synaptic plasticity in
      hippocampal slices of aged (22-24 months) and young adult (4-6 months) male
      Fischer 344 rats was investigated. Prolonged 1 Hz stimulation (900 pulses) of
      Schaffer collaterals, which normally depresses CA3/CA1 synaptic strength in aged
      rat slices, failed to induce long-term depression (LTD) during bath application
      of the L-channel antagonist nifedipine (10 microM). When 5 Hz stimulation (900
      pulses) was used to modify synaptic strength, nifedipine facilitated synaptic
      enhancement in slices from aged, but not young, adult rats. This enhancement was
      pathway-specific, reversible, and impaired by the NMDA receptor (NMDAR)
      antagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Induction of long-term
      potentiation (LTP) in aged rats, using 100 Hz stimulation, occluded subsequent
      synaptic enhancement by 5 Hz stimulation, suggesting that nifedipine-facilitated
      enhancement shares mechanisms in common with conventional LTP. Facilitation of
      synaptic enhancement by nifedipine likely was attributable to a reduction (
      approximately 30%) in the Ca2+-dependent K+-mediated afterhyperpolarization
      (AHP), because the K+ channel blocker apamin (1 microM) similarly reduced the AHP
      and promoted synaptic enhancement by 5 Hz stimulation. In contrast, apamin did
      not block LTD induction using 1 Hz stimulation, suggesting that, in aged rats,
      the AHP does not influence LTD and LTP induction in a similar way. The results
      indicate that, during aging, L-channels can (1) facilitate LTD induction during
      low rates of synaptic activity and (2) impair LTP induction during higher levels
      of synaptic activation via an increase in the Ca2+-dependent AHP.

PMID- 9547226
TI  - Increased synaptic sprouting in response to estrogen via an apolipoprotein E
      dependent mechanism: implications for Alzheimer's disease.
AB  - Estrogen replacement therapy appears to delay the onset of Alzheimer's disease
      (AD), but the mechanisms for this action are incompletely known. We show how the
      enhancement of synaptic sprouting by estradiol (E2) in response to an entorhinal
      cortex (EC) lesion model of AD may operate via an apolipoprotein E (apoE)
      dependent mechanism. In wild-type (WT) mice, ovariectomy decreased
      commissural/associational sprouting to the inner molecular layer of the dentate
      gyrus, with synaptophysin (SYN) as a marker. E2 replacement returned SYN in the
      inner layer to levels of EC-lesioned, ovary-bearing controls and increased the
      area of compensatory synaptogenesis in the outer molecular layer. In EC-lesioned
      apoE-knock-out (KO) mice, however, E2 did not enhance sprouting. We also examined
      apoJ (clusterin) mRNA, which is implicated in AD by its presence in senile
      plaques, its transport of Abeta across the blood-brain barrier, and its induction
      by neurodegenerative lesioning. ApoJ mRNA levels were increased by E2 replacement
      in EC-lesioned WT mice but not in apoE-KO mice. These data suggest a mechanism
      for the protective effects of estrogens on AD and provide a link between two
      important risk factors in the etiology of AD, the apoE epsilon4 genotype and an
      estrogen-deficient state. This is also the first evidence that SYN, a presynaptic
      protein involved in neurotransmitter release, is regulated by E2 in the adult
      brain, and that apoE is necessary for the induction of apoJ mRNA by E2 in brain
      injury.

PMID- 9547227
TI  - Type I adenylyl cyclase mutant mice have impaired mossy fiber long-term
      potentiation.
AB  - Long-term potentiation (LTP) at the mossy fiber-->CA3 pyramidal cell synapse in
      the hippocampus is an NMDA-independent form of LTP that requires cAMP-dependent
      protein kinase (PKA) activity and can be induced by forskolin, a general
      activator of adenylyl cyclases. Presynaptic Ca2+ influx and elevated cAMP may be
      obligatory for mossy fiber LTP. Because the Ca2+-stimulated type 1 adenylyl
      cyclase (AC1) is expressed in the dentate gyrus and CA3 pyramidal cells, it is
      hypothesized that AC1 may be critical for mossy fiber LTP. To test this
      hypothesis, we examined several forms of hippocampal LTP in wild-type and AC1
      mutant mice. Wild-type and AC1 mutant mice exhibited comparable perforant path
      LTP recorded in the dentate gyrus as well as decremental LTP at the Schaffer
      collateral-->CA1 pyramidal cell synapse. Although the mutant mice exhibited
      normal paired pulse facilitation, mossy fiber LTP was impaired significantly in
      AC1 mutants. High concentrations of forskolin induced mossy fiber LTP to
      comparable levels in wild-type and AC1 mutant mice, indicating that signaling
      components downstream from the adenylyl cyclase, including PKA, ion channels, and
      secretory machinery, were not affected by disruption of the AC1 gene. These data
      indicate that coupling of Ca2+ to activation of AC1 is crucial for mossy fiber
      LTP, most likely via activation of PKA and enhancement of excitatory amino acid
      secretion.

PMID- 9547228
TI  - Calcium-sensitive particulate guanylyl cyclase as a modulator of cAMP in
      olfactory receptor neurons.
AB  - The second messengers cAMP and inositol-1,4,5-triphosphate have been implicated
      in olfaction in various species. The odorant-induced cGMP response was
      investigated using cilia preparations and olfactory primary cultures. Odorants
      cause a delayed and sustained elevation of cGMP. A component of this cGMP
      response is attributable to the activation of one of two kinetically distinct
      cilial receptor guanylyl cyclases by calcium and a guanylyl cyclase-activating
      protein (GCAP). cGMP thus formed serves to augment the cAMP signal in a cGMP
      dependent protein kinase (PKG) manner by direct activation of adenylate cyclase.
      cAMP, in turn, activates cAMP-dependent protein kinase (PKA) to negatively
      regulate guanylyl cyclase, limiting the cGMP signal. These data demonstrate the
      existence of a regulatory loop in which cGMP can augment a cAMP signal, and in
      turn cAMP negatively regulates cGMP production via PKA. Thus, a small, localized,
      odorant-induced cAMP response may be amplified to modulate downstream
      transduction enzymes or transcriptional events.

PMID- 9547229
TI  - Experience-induced neurogenesis in the senescent dentate gyrus.
AB  - We demonstrate here that under physiological conditions neurogenesis continues to
      occur in the dentate gyrus of senescent mice and can be stimulated by living in
      an enriched environment. Neurogenesis was investigated by confocal microscopy of
      three-channel immunofluorescent staining for the proliferation marker
      bromodeoxyuridine (BrdU) and neuronal and glial markers. Quantification was
      performed with unbiased stereological counting techniques. Neurogenesis decreased
      with increasing age. Stimulation of adult and aged mice by switching from
      standard housing to an enriched environment with opportunities for social
      interaction, exploration, and physical activity for 68 d resulted in an increased
      survival of labeled cells. Phenotypic analysis revealed that, in enriched living
      animals, relatively more cells differentiated into neurons, resulting in a
      threefold net increase of BrdU-labeled neurons in 20-month-old mice (105 vs 32
      cells) and a more than twofold increase in 8-month-old mice (684 vs 285 cells)
      compared with littermates living under standard laboratory conditions.
      Corresponding absolute numbers of BrdU-positive astrocytes and BrdU-positive
      cells that did not show colabeling for neuronal or glial markers were not
      influenced. The effect on the relative distribution of phenotypes can be
      interpreted as a survival-promoting effect that is selective for neurons.
      Proliferation of progenitor cells appeared unaffected by environmental
      stimulation.

PMID- 9547230
TI  - Stable complexes involving acetylcholinesterase and amyloid-beta peptide change
      the biochemical properties of the enzyme and increase the neurotoxicity of
      Alzheimer's fibrils.
AB  - Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-beta
      peptide (Abeta) during its assembly into filaments, in agreement with its
      colocalization with the Abeta deposits of Alzheimer's brain. The association of
      the enzyme with nascent Abeta aggregates occurs as early as after 30 min of
      incubation. Analysis of the catalytic activity of the AChE incorporated into
      these complexes shows an anomalous behavior reminiscent of the AChE associated
      with senile plaques, which includes a resistance to low pH, high substrate
      concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the
      toxicity of the AChE-amyloid complexes is higher than that of the Abeta
      aggregates alone. Thus, in addition to its possible role as a heterogeneous
      nucleator during amyloid formation, AChE, by forming such stable complexes, may
      increase the neurotoxicity of Abeta fibrils and thus may determine the selective
      neuronal loss observed in Alzheimer's brain.

PMID- 9547231
TI  - High constitutive NF-kappaB activity mediates resistance to oxidative stress in
      neuronal cells.
AB  - Selected clones of the sympathetic precursor-like cell line PC12 (rCl8) are
      resistant to oxidative cell death induced by the Alzheimer's disease-associated
      amyloid beta protein (Abeta) and hydrogen peroxide (H2O2). Here, we show that the
      transcriptional activity and DNA binding activity of the redox-sensitive
      transcription factor NF-kappaB and its nuclear expression are constitutively
      increased in rCl8 cells compared with their nonresistant parental PC12 cell
      (PC12p) counterpart. Suppression of the transcriptional activity of NF-kappaB in
      rCl8 cells with the synthetic glucocorticoid dexamethasone or by direct
      overexpression of a super-repressor mutant form of IkappaBalpha, a specific
      inhibitor of NF-kappaB, reversed the oxidative stress resistance phenotype of
      these cells and ultimately led to increased cell death after the challenge with
      H2O2. Dexamethasone treatment also caused an increase in the protein level of
      IkappaBalpha. Our data show that an increased baseline of NF-kappaB activity may
      mediate the resistance of these cells of neuronal origin to oxidative stress.
      Therefore, the presented model may help to identify possible neuronal target
      genes of NF-kappaB and to further elucidate the molecular basis of the
      differential sensitivity of neurons in neurodegenerative conditions associated
      with an increased oxidative burden, such as in Alzheimer's disease.

PMID- 9547232
TI  - Attenuated influx of calcium ions at nerve endings of csp and shibire mutant
      Drosophila.
AB  - Previous work has shown that cysteine-string proteins (csps) are synaptic vesicle
      proteins that are important for evoked neurotransmitter release at Drosophila
      neuromuscular junctions. Indirect evidence has implicated csps in a regulatory
      link between synaptic vesicles and presynaptic calcium (Ca) channels. In this
      report, we use Ca Crimson to monitor stimulus-dependent changes of cytosolic Ca
      at motor nerve terminals of csp mutant Drosophila. These mutants display
      temperature-sensitive (TS) paralysis and a presynaptic failure of evoked synaptic
      transmission. We show that this TS inhibition of neuromuscular transmission is
      correlated with a block of Ca ion entry at nerve endings of csp mutants. These
      data support the hypothesis that csps mediate a regulatory interaction between
      synaptic vesicles and presynaptic Ca channels. Moreover, these results predict
      that if one depletes nerve endings of synaptic vesicles, one may see a reduction
      of presynaptic Ca ion entry. Defects of the dynamin gene in TS shibire mutant
      Drosophila interfere with synaptic vesicle recycling and lead to an activity
      dependent depletion of these organelles. Our results show that Ca influx is
      blocked at nerve terminals of shibire mutant larvae at the same time that
      synaptic transmission fails in these organisms. Thus, using two completely
      independent Drosophila mutants, we demonstrate that synaptic vesicles and csps
      are vital for the function of presynaptic Ca channels.

PMID- 9547233
TI  - Massive mitochondrial degeneration in motor neurons triggers the onset of
      amyotrophic lateral sclerosis in mice expressing a mutant SOD1.
AB  - Amyotrophic lateral sclerosis (ALS) involves motor neuron degeneration, skeletal
      muscle atrophy, paralysis, and death. Mutations in Cu,Zn superoxide dismutase
      (SOD1) are one cause of the disease. Mice transgenic for mutated SOD1 develop
      symptoms and pathology similar to those in human ALS. To understand the disease
      mechanism, we developed a simple behavioral assay for disease progression in
      mice. Using this assay, we defined four stages of the disease in mice expressing
      G93A mutant SOD1. By studying mice with defined disease stages, we tied several
      pathological features into a coherent sequence of events leading to motor neuron
      death. We show that onset of the disease involves a sharp decline of muscle
      strength and a transient explosive increase in vacuoles derived from degenerating
      mitochondria, but little motor neuron death. Most motor neurons do not die until
      the terminal stage, approximately 9 weeks after disease onset. These results
      indicate that mutant SOD1 toxicity is mediated by damage to mitochondria in motor
      neurons, and this damage triggers the functional decline of motor neurons and the
      clinical onset of ALS. The absence of massive motor neuron death at the early
      stages of the disease indicates that the majority of motor neurons could be
      rescued after clinical diagnosis.

PMID- 9547234
TI  - Traumatic spinal cord injury induces nuclear factor-kappaB activation.
AB  - Inflammatory responses are a major component of secondary injury and play a
      central role in mediating the pathogenesis of acute and chronic spinal cord
      injury (SCI). The nuclear factor-kappaB (NF-kappaB) family of transcription
      factors is required for the transcriptional activation of a variety of genes
      regulating inflammatory, proliferative, and cell death responses of cells. In
      this study we examined the temporal and cellular expression of activated NF
      kappaB after traumatic SCI. We used a contusion model (N.Y.U. Impactor) to
      initiate the early biochemical and molecular changes that occur after traumatic
      injury to reproduce the pathological events associated with acute inflammation
      after SCI. The activation and cellular distribution of activated NF-kappaB was
      evaluated by using a monoclonal antibody that selectively recognizes activated
      p65 in a NF-kappaB dimer. Immunohistochemical and Western blot analyses
      demonstrated that NF-kappaB activation occurred as early as 0.5 hr postinjury and
      persisted for at least 72 hr. Using electrophoretic mobility shift assays (EMSA),
      we demonstrate that NF-kappaB is activated after SCI. In our immunohistochemical,
      Western, and EMSA experiments there are detectable levels of activated NF-kappaB
      in our control animals. Using double-staining protocols, we detected activated NF
      kappaB in macrophages/microglia, endothelial cells, and neurons within the
      injured spinal cord. Colocalization of activated NF-kappaB with the NF-kappaB
      dependent gene product, inducible nitric oxide synthase (iNOS), suggests
      functional implications for this transcription factor in the pathogenesis of
      acute spinal cord injury. Although there is considerable evidence for the
      involvement of an inflammatory reaction after traumatic SCI, this is the first
      evidence for the activation of NF-kappaB after trauma. Strategies directed at
      blocking the initiation of this cascade may prove beneficial as a therapeutic
      approach for the treatment of acute SCI.

PMID- 9547235
TI  - Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice:
      astrocyte-specific expression and differing biological effects of astrocyte
      secreted apoE3 and apoE4 lipoproteins.
AB  - The epsilon4 allele of apolipoprotein E (apoE) is associated with increased risk
      for Alzheimer's disease (AD) and poor outcome after brain injury. In the CNS,
      apoE is expressed by glia, predominantly astrocytes. To define the potential
      biological functions of different human apoE isoforms produced within the brain,
      transgenic mice were generated in which human apoE3 and apoE4 expression is under
      control of the astrocyte-specific glial fibrillary acidic protein (GFAP)
      promoter. These animals were then bred back to apoE knock-out mice. Human apoE
      protein is found within astrocytes and the neuropil throughout development and
      into the adult period, as assessed by immunocytochemistry and immunoblot analysis
      in several GFAP-apoE3 and E4 lines. Cultured astrocytes from these mice secrete
      apoE3 and apoE4 in lipoproteins that are high-density lipoprotein-like in size.
      When primary hippocampal neurons are grown in the presence of astrocyte
      monolayers derived from these transgenic mice, there is significantly greater
      neurite outgrowth from neurons grown in the presence of apoE3-secreting
      astrocytes compared with apoE4-secreting or apoE knock-out astrocytes. These
      effects are not dependent on direct astrocyte-neuron contact and appear to
      require the low-density lipoprotein receptor-related protein. These data suggest
      that astrocyte-secreted, apoE3-containing lipoproteins have different biological
      effects than apoE4-containing lipoproteins. In addition to providing information
      regarding the role of astrocyte-secreted apoE lipoproteins in the normal brain,
      these animals will also be useful in models of both AD and CNS injury.

PMID- 9547236
TI  - Competitive signaling between TrkA and p75 nerve growth factor receptors
      determines cell survival.
AB  - In addition to its role as a survival factor, nerve growth factor (NGF) has been
      implicated in initiating apoptosis in restricted cell types both during
      development and after terminal cell differentiation. NGF binds to the TrkA
      tyrosine kinase and the p75 neurotrophin receptor, a member of the tumor necrosis
      factor cytokine family. To understand the mechanisms underlying survival versus
      death decisions, the TrkA receptor was introduced into oligodendrocyte cell
      cultures that undergo apoptosis in a p75-dependent manner. Here we report that
      activation of the TrkA NGF receptor in oligodendrocytes negates cell death by the
      p75 receptor. TrkA-mediated rescue from apoptosis correlated with mitogen
      activated protein kinase activation. Concurrently, activation of TrkA in
      oligodendrocytes resulted in suppression of c-jun kinase activity initiated by
      p75, whereas induction of NFkappaB activity by p75 was unaffected. These results
      indicate that TrkA-mediated rescue involves not only activation of survival
      signals but also simultaneous suppression of a death signal by p75. The selective
      interplay between tyrosine kinase and cytokine receptors provides a novel
      mechanism that achieves alternative cellular responses by merging signals from
      different ligand-receptor systems.

PMID- 9547237
TI  - Regeneration of cochlear efferent nerve terminals after gentamycin damage.
AB  - Chickens recover auditory function after hair cell loss caused by ototoxic drug
      damage or acoustic overstimulation, indicating that mechanisms exist to
      reestablish appropriate neuronal connections to regenerated hair cells. However,
      despite similar hair cell regeneration times, hearing recovery takes
      substantially longer after aminoglycoside than after sound damage. We have
      therefore begun examining damage and regeneration of efferent nerve terminals by
      immunolabeling whole-mount cochleae for differentially localized synaptic
      proteins and by visualizing the distribution of label with confocal microscopy.
      In undamaged cochleae, the synaptic proteins synapsin and syntaxin show similar
      distribution patterns corresponding to the large cup-like terminals on short hair
      cells. After gentamycin administration, these terminals are disrupted as hair
      cells are lost, leaving smaller, more numerous synapsin-reactive structures in
      the sensory epithelium. Syntaxin reactivity remains associated with the extruded
      hair cells, indicating that the presynaptic membrane is still attached to the
      postsynaptic site. In contrast, after sound damage, both synapsin and syntaxin
      reactivity are lost from the epithelium with extruded hair cells. As regenerated
      hair cells differentiate after gentamycin treatment, the synapsin labeling
      associated with cup-like efferent endings reappears but is not completely
      restored even after 60 d of recovery. Thus, efferent terminals are reestablished
      much more slowly than after sound damage (), consistent with the prolonged loss
      of hearing function. This in vivo model system allows comparison of axonal
      reconnection after either complete loss (sound damage) or partial disruption
      (gentamycin treatment) of axon terminals. Elucidating the differences in recovery
      between these injuries can provide insights into reinnervation mechanisms.

PMID- 9547238
TI  - Selective fasciculation and divergent pathfinding decisions of embryonic chick
      motor axons projecting to fast and slow muscle regions.
AB  - Proper motor function requires the precise matching of motoneuron and muscle
      fiber properties. The lack of distinguishing markers for early motoneurons has
      made it difficult to determine whether this matching is established by selective
      innervation during development or later via motoneuron-muscle fiber interactions.
      To examine whether chick motoneurons selectively innervate regions of their
      target containing either fast or slow muscle fibers, we backlabeled neurons from
      each of these regions with lipophilic dyes. We found that motor axons projecting
      to fast and slow muscle regions sorted into separate but adjacent fascicles
      proximally in the limb, long before they reached the muscle. More distally, these
      fascicles made divergent pathfinding decisions to course directly to the
      appropriate muscle fiber region. In contrast, axons projecting to different areas
      of an all-fast muscle did not fasciculate separately and became more intermingled
      as they coursed through the limb. Selective fasciculation of fast- and slow
      projecting motoneurons was similar both before and after motoneuron cell death,
      suggesting that motoneurons specifically recognized and fasciculated with axons
      growing to muscle regions containing the appropriate muscle fiber type. Taken
      together, these results strongly support the hypothesis that "fast" and "slow"
      motoneurons are molecularly distinct before target innervation and that they use
      these differences to selectively fasciculate, pathfind to, and branch within the
      correct muscle fiber region from the outset of neuromuscular development.

PMID- 9547239
TI  - Development of bone morphogenetic protein receptors in the nervous system and
      possible roles in regulating trkC expression.
AB  - Characterization of bone morphogenetic protein receptor (BMPR) expression during
      development is necessary for understanding the role of these factors during
      neural maturation. In this study, in situ hybridization analyses demonstrate that
      BMP-specific type I (BMPR-IA and BMPR-IB) and type II (BMPR-II) receptor mRNAs
      are expressed at significant levels in multiple regions of the CNS, cranial
      ganglia, and peripheral sensory and autonomic ganglia during the embryonic and
      neonatal periods. All three BMP receptor subunits are expressed within
      periventricular generative zones. BMPR-IA is more abundant than the other
      receptor subtypes, with widespread expression in the brain, cranial ganglia, and
      peripheral ganglia. By contrast, BMPR-IB mRNA displays significant expression
      within more restricted regions, including the anterior olfactory nuclei. BMPR-II
      mRNA exhibits peak expression within the cerebellar Purkinje cell layer and the
      hippocampus, as well as within cranial ganglia. The distribution of BMP receptors
      within large neurons in adult dorsal root ganglia suggested a possible role in
      regulating expression of the neurotrophin receptor trkC. This hypothesis was
      tested in explant cultures of embryonic day 15 (E15) and postnatal day 1 (P1)
      sympathetic superior cervical ganglia (SCG). Treatment of the E15 or the P1 SCG
      with BMP-2 induced expression of trkC mRNA and responsiveness of sympathetic
      neurons to NT3 as measured by neurite outgrowth. The pattern of expression of BMP
      receptors in embryonic brain suggests several potentially novel areas for further
      developmental analysis and supports numerous recent studies that indicate that
      BMPs have a broad range of cellular functions during neural development and in
      adult life.

PMID- 9547240
TI  - Development of the mouse inner ear and origin of its sensory organs.
AB  - The molecular mechanisms dictating the morphogenesis and differentiation of the
      mammalian inner ear are largely unknown. To better elucidate the normal
      development of this organ, two approaches were taken. First, the membranous
      labyrinths of mouse inner ears ranging from 10.25 to 17 d postcoitum (dpc) were
      filled with paint to reveal their gross development. Particular attention was
      focused on the developing utricle, saccule, and cochlea. Second, we used bone
      morphogenetic protein 4 (BMP4) and lunatic fringe (Fng) as molecular markers to
      identify the origin of the sensory structures. Our data showed that BMP4 was an
      early marker for the superior, lateral, and posterior cristae, whereas Fng served
      as an early marker for the macula utriculi, macula sacculi, and the sensory
      portion of the cochlea. The posterior crista was the first organ to appear at
      11.5 dpc and was followed by the superior crista, the lateral crista, and the
      macula utriculi at 12 dpc. The macula sacculi and the cochlea were present at 12
      dpc but became distinguishable from each other by 13 dpc. Based on the gene
      expression patterns, the anterior and lateral cristae may share a common origin.
      Similarly, three sensory organs, the macula utriculi, macula sacculi, and
      cochlea, seem to arise from a single region of the otocyst.

PMID- 9547241
TI  - Light-induced retinal degeneration suppresses developmental progression of flip
      to-flop alternative splicing in GluR1.
AB  - AMPA receptors are hetero-oligomers composed of subsets of four distinct
      subunits, termed GluR1, GluR2, GluR3, and GluR4. Using quantitative reverse
      transcription-PCR analysis, we have found that light-induced degeneration of rat
      retina dramatically suppresses developmental progression of the flip-to-flop
      alternative splicing switch of retinal GluR1 mRNA. When animals were raised under
      standard conditions of a 12 hr light/dark cycle (LD 12:12), the flop-to-flip
      ratio in GluR1 and GluR2 dramatically increased between postnatal day 10 (P10)
      and P28, and the ratios continued to increase gradually up to P84. When animals
      were raised in complete darkness, this increase was delayed in GluR1 between P21
      and P42. In addition, the increase of the flop-to-flip ratio in GluR1 was
      strongly suppressed after P21 under conditions of continuous illumination from
      P2. This is significant because P21 is just after the eye opening and is the
      timing of the onset of light-induced retinal degeneration. This suppression of
      the increase of the flop-to-flip ratio was specific to GluR1 and was not observed
      in GluR2-4. Immunocytochemistry and immunoblot analysis suggested no changes in
      either the distribution or expression of GluR1 protein in the light-damaged
      retina measured at P84. When rats were raised under continuous illumination from
      P2 to P21 followed by LD 12:12 from P22 to P84, retinal degeneration did not
      progress after P22. In such animals the flop-to-flip ratio, once decreased to
      approximately 50% of the control (LD 12:12) at P21, was restored to the control
      level at P84. These findings demonstrate that developmental progression of the
      flip-to-flop exon switch in retinal GluR1 is affected by lighting conditions, and
      that light-induced retinal degeneration contributes to the mechanism of
      suppression of this splicing switch.

PMID- 9547242
TI  - Bcl-2 accelerates the maturation of early sensory neurons.
AB  - Bcl-2 is a cytoplasmic protein that blocks apoptosis in a wide variety of cell
      types. Here we report a novel role for Bcl-2 in the early stages of neuronal
      development. Shortly after differentiating from progenitor cells, sensory neurons
      undergo a distinct morphological change; initially they have small, spindle
      shaped, phase-dark cell bodies that become large, spherical, and phase-bright.
      Early sensory neurons cultured from the trigeminal ganglia of bcl-2-/- embryos at
      embryonic day 11 (E11) and E12 underwent this change more slowly than trigeminal
      neurons of wild-type embryos of the same ages. The delay was not attributable to
      the well documented role of Bcl-2 in preventing apoptosis, because Bcl-2
      deficient early sensory neurons survived as well as wild-type neurons.
      Accordingly, there was a significantly smaller number of the more mature type of
      neuron in the early trigeminal ganglia of bcl-2-/- embryos, yet the number of
      neurons in the trigeminal ganglia of bcl-2-/- and wild-type embryos was similar.
      The absence of Bcl-2 did not cause a uniform delay in the developmental program
      of sensory neurons, because the time course of nerve growth factor receptor
      expression (both trkA and p75) was unaffected in the trigeminal neurons of bcl-2
      /- embryos. These findings indicate that Bcl-2 expression is required for the
      normal progression of a particular early maturational change in embryonic sensory
      neurons.

PMID- 9547243
TI  - Brain-derived neurotrophic factor modulates the development of the dopaminergic
      network in the rodent retina.
AB  - Dopaminergic cells in the retina express the receptor for brain-derived
      neurotrophic factor (BDNF) (). To investigate whether BDNF can influence the
      development of the retinal dopaminergic pathway, we performed intraocular
      injections of BDNF during the second or third postnatal week and visualized the
      dopaminergic system with tyrosine hydroxylase (TH) immunohistochemistry. Both
      regimens of BDNF treatment caused an increase in TH immunoreactivity in stratum 1
      and stratum 3 of the inner plexiform layer (IPL). D2 dopamine receptor
      immunoreactivity, a presynaptic marker of dopaminergic cells (), was also
      increased in stratum 1 and stratum 3 of the inner plexiform layer. These data
      suggest that BDNF causes sprouting of dopaminergic fibers in the inner plexiform
      layer. Other neurochemical systems, for example, the cholinergic amacrine cells,
      remained unaffected. Similar effects were observed after injections of
      neurotrophin-3 and neurotrophin-4, but not nerve growth factor. Analysis of whole
      mounted TH-immunolabeled retinae revealed hypertrophy of dopaminergic cells (+41%
      in soma areas; p < 0.01) and an increase of labeled dopaminergic varicosities in
      stratum 1 of the IPL (+51%; p < 0.01) after BDNF treatment. The opposite was
      observed in mice homozygous for a null mutation of the bdnf gene: dopaminergic
      cells were atrophic (-22.5% in soma areas; p < 0.05), and the density of TH
      positive varicosities in stratum 1 was reduced (57%; p < 0.01). We conclude that
      BDNF controls the development of the retinal dopaminergic network and may be
      particularly important in determining the density of dopaminergic innervation in
      the retina.

PMID- 9547244
TI  - Neurolin, the goldfish homolog of DM-GRASP, is involved in retinal axon
      pathfinding to the optic disk.
AB  - Young axons of new retinal ganglion cells (RGCs) in the continuously growing
      goldfish retina fasciculate with one another and their immediate forerunners on
      their path toward the optic disk and along the optic nerve. They express the
      immunoglobulin superfamily cell adhesion molecules (CAMs) neurolin (DM-GRASP) and
      the L1-like E587 antigen. Repeated injections of Fab fragments from polyclonal
      antisera against neurolin (neurolin Fabs) into the eye of 3. 4-cm-long and
      rapidly growing goldfish caused highly aberrant pathways of young RGC axon
      subfascicles in the dorsal retina. Many axons grew in circles and failed to reach
      the optic disk. In contrast, E587 Fabs, used in parallel experiments, disrupted
      the fascicles but did not interfere with the disk-directed growth. Neurolin Fabs
      also disturbed axonal fasciculation in vivo as well as in vitro but less severely
      than E587 Fabs. Coinjections of both Fabs increased defasciculation of the dorsal
      axons in both aberrant and disk-directed routes. They also disrupted the order of
      young RGC axons in the optic nerve more severely than E587 Fabs alone. This
      demonstrates that the development of tight and orderly fascicles in the dorsal
      retina and in the optic nerve requires both E587 antigen and neurolin. More
      importantly, our results suggest an involvement of neurolin in RGC axonal
      guidance from the retinal periphery to the optic disk. Because disrupted
      fascicles and errant axon routes were found only in the dorsal retinal half, a
      cooperation with so-called positional markers may be conceived.

PMID- 9547245
TI  - Microcircuitry and mosaic of a blue-yellow ganglion cell in the primate retina.
AB  - Perception of hue is opponent, involving the antagonistic comparison of signals
      from different cone types. For blue versus yellow opponency, the antagonism is
      first evident at a ganglion cell with firing that increases to stimulation of
      short wavelength-sensitive (S) cones and decreases to stimulation of middle
      wavelength-sensitive (M) and long wavelength-sensitive (L) cones. This ganglion
      cell, termed blue-yellow (B-Y), has a distinctive morphology with dendrites in
      both ON and OFF strata of the inner plexiform layer (Dacey and Lee, 1994). Here
      we report the synaptic circuitry of the cell and its spatial density.
      Reconstructing neurons in macaque fovea from electron micrographs of serial
      sections, we identified six ganglion cells that branch in both strata and have
      similar circuitry. In the ON stratum each cell collects approximately 33 synapses
      from bipolar cells traced back exclusively to invaginating contacts from S cones,
      and in the OFF stratum each cell collects approximately 14 synapses from bipolar
      cells (types DB2 and DB3) traced to basal synapses from approximately 20 M and L
      cones. This circuitry predicts that spatially coincident blue-yellow opponency
      arises at the level of the cone output via expression of different glutamate
      receptors. S cone stimuli suppress glutamate release onto metabotropic receptors
      of the S cone bipolar cell dendrite, thereby opening cation channels, whereas M
      and L cone stimuli suppress glutamate release onto ionotropic glutamate receptors
      of DB2 and DB3 cell dendrites, thereby closing cation channels. Although the B-Y
      cell is relatively rare (3% of foveal ganglion cells), its spatial density equals
      that of the S cone; thus it could support psychophysical discrimination of a blue
      yellow grating down to the spatial cutoff of the S cone mosaic.

PMID- 9547246
TI  - GABAergic cells are the major postsynaptic targets of mossy fibers in the rat
      hippocampus.
AB  - Dentate granule cells communicate with their postsynaptic targets by three
      distinct terminal types. These include the large mossy terminals, filopodial
      extensions of the mossy terminals, and smaller en passant synaptic varicosities.
      We examined the postsynaptic targets of mossy fibers by combining in vivo
      intracellular labeling of granule cells, immunocytochemistry, and electron
      microscopy. Single granule cells formed large, complex "mossy" synapses on 11-15
      CA3 pyramidal cells and 7-12 hilar mossy cells. In contrast, GABAergic
      interneurons, identified with immunostaining for substance P-receptor,
      parvalbumin, and mGluR1a-receptor, were selectively innervated by very thin
      (filopodial) extensions of the mossy terminals and by small en passant boutons in
      both the hilar and CA3 regions. These terminals formed single, often perforated,
      asymmetric synapses on the cell bodies, dendrites, and spines of GABAergic
      interneurons. The number of filopodial extensions and small terminals was 10
      times larger than the number of mossy terminals. These findings show that in
      contrast to cortical pyramidal neurons, (1) granule cells developed distinct
      types of terminals to affect interneurons and pyramidal cells and (2) they
      innervated more inhibitory than excitatory cells. These findings may explain the
      physiological observations that increased activity of granule cells suppresses
      the overall excitability of the CA3 recurrent system and may form the structural
      basis of the target-dependent regulation of glutamate release in the mossy fiber
      system.

PMID- 9547247
TI  - Patchy distribution of NMDAR1 subunit immunoreactivity in developing visual
      cortex.
AB  - Development of ocular dominance columns is dependent on patterned retinal
      activity, and yet patterned activity alone cannot explain all aspects of cortical
      column development. Features intrinsic to the cortex have been proposed to
      interact with activity to guide the patterning of cortical columns (), and the
      NMDA receptor, because of its role in experience-dependent plasticity, is an
      obvious candidate. Using immunohistochemical techniques, we found a transiently
      patchy distribution of the NMDA receptor 1 (NMDAR1) subunit in kitten visual
      cortex. Regularly spaced patches of NMDAR1-immunoreactive neurons were found at
      the top of the cortical plate in the developing visual cortex at 2 weeks of age.
      At 4-5 weeks of age, the radial extent of the NMDAR1 patches spanned the
      supragranular layers, and by 12 weeks of age, this nonuniform pattern of NMDAR1
      immunostaining was no longer apparent. Monocular visual experience prevented the
      expression of the NMDAR1 patches, but just 4 d of subsequent binocular visual
      experience was sufficient to promote expression of the patches. Furthermore, the
      NMDAR1 patches tended to be associated with the borders of ocular dominance
      columns. These results suggest that the degree of plasticity associated with NMDA
      mediated mechanisms is elevated in local regions across the tangential extent of
      the visual cortex and that the NMDAR1 patches may participate in sculpting the
      overall arrangement of visual cortical columns.

PMID- 9547248
TI  - Calcium waves precede electrophysiological changes of spreading depression in
      hippocampal organ cultures.
AB  - Although intercellular Ca2+ waves resemble spreading depression (SD) and occur in
      hippocampal organ cultures (HOTCs), SD has not been reported in these cultures.
      Accordingly, electrophysiological and Ca2+ imaging techniques were used to
      examine potential interrelations between Ca2+ waves and electrophysiological
      changes of SD. Our results show, for the first time, that HOTCs can support SD.
      Furthermore, two distinct Ca2+ waves were found to precede SD. The first traveled
      >100 micron/sec along the pyramidal cell dendritic layer. The second subsequently
      traveled mostly perpendicular to the pyramidal cell layer from CA3 (or CA1) but
      also in all directions from its area of initiation. This second, slower wave
      spread with the interstitial DC change of SD at millimeters per minute but always
      ahead of it by 6-16 sec. Heptanol, which uncouples gap junctions, blocked both of
      these Ca2+ waves and SD. Thus, two types of Ca2+ waves occur with the initiation
      and propagation of SD. The first might reflect interneuronal changes linked by
      gap junctions, whereas the second might stem from interastrocyte changes linked
      via similar connections. Because individual cells can be followed in space and
      time for protracted periods in HOTCs, this preparation may be ideal for studies
      designed to explore not only the mechanisms of SD but also the long-term
      consequences of SD, such as ischemic tolerance.

PMID- 9547249
TI  - Distinct regions of the periaqueductal gray are involved in the acquisition and
      expression of defensive responses.
AB  - In fear conditioning, a rat is placed in a distinct environment and delivered
      footshock. The response to the footshock itself is called an activity burst and
      includes running, jumping, and vocalization. The fear conditioned to the distinct
      environment by the footshock elicits complete immobility termed freezing. Lesions
      of the ventral periaqueductal gray (vPAG) strongly attenuate freezing. However,
      lesions of the dorsolateral periaqueductal gray (dlPAG) increase the amount of
      freezing seen to conditional fear cues acquired under conditions in which intact
      rats do not demonstrate much fear conditioning. To examine the necessity of these
      regions in the acquisition and expression of fear, we performed five experiments
      that examined the effects of electrolytic lesions of the dlPAG and the vPAG in
      learned and unlearned fear. In experiment 1, lesions of the vPAG strongly
      attenuated, whereas lesions of the dlPAG enhanced, unconditional freezing to a
      cat. In experiment 2, lesions of the dlPAG made before but not after training
      enhanced the amount of freezing shown to conditional fear cues acquired via
      immediate footshock delivery. In experiment 3, vPAG lesions made either before or
      after training with footshock decreased the level of freezing to conditional fear
      cues. Neither dlPAG lesions nor vPAG lesions affected footshock sensitivity
      (experiment 4) or consumption on a conditioned taste aversion test that does not
      elicit antipredator responses (experiment 5). On the basis of these results, it
      is proposed that activation of the dlPAG produces inhibition of the vPAG and
      forebrain structures involved with defense. In contrast, the vPAG seems to be
      necessary for postencounter freezing defensive behavior.

PMID- 9547250
TI  - Muscle response to changing neuronal input in the lobster (Panulirus interruptus)
      stomatogastric system: slow muscle properties can transform rhythmic input into
      tonic output.
AB  - Slow, non-twitch muscles are widespread in lower vertebrates and invertebrates
      and are often assumed to be primarily involved in posture or slow motor patterns.
      However, in several preparations, including some well known invertebrate "model"
      preparations, slow muscles are driven by rapid, rhythmic inputs. The response of
      slow muscles to such inputs is little understood. We are investigating this issue
      with a slow stomatogastric muscle (cpv1b) driven by a relatively rapid, rhythmic
      neural pattern. A simple model suggests that as cycle period decreases, slow
      muscle contractions show increasing intercontraction temporal summation and at
      steady state consist of phasic contractions overlying a tonic contracture. We
      identify five components of these contractions: total, average, tonic, and phasic
      amplitudes, and percent phasic (phasic amplitude divided by total amplitude).
      cpv1b muscle contractions induced by spontaneous rhythmic neural input in vitro
      consist of phasic and tonic components. Nerve stimulation at varying cycle
      periods and constant duty cycle shows that a tonic component is always present,
      and at short periods the muscle transforms rhythmic input into almost completely
      tonic output. Varying spike frequency, spike number, and cycle period show that
      frequency codes total, average, and tonic amplitudes, number codes phasic
      amplitude, and period codes percent phasic. These data suggest that tonic
      contraction may be a property of slow muscles driven by rapid, rhythmic input,
      and in these cases it is necessary to identify the various contraction components
      and their neural coding. Furthermore, the parameters that code these components
      are interdependent, and control of slow muscle contraction is thus likely
      complex.

PMID- 9547251
TI  - Mechanisms of cortical reorganization in lower-limb amputees.
AB  - The human motor system undergoes reorganization after amputation, but the site of
      motor reorganization and the mechanisms involved are unknown. We studied the site
      and mechanisms of motor reorganization in 16 subjects with traumatic lower-limb
      amputation. Stimulation at different levels in the CNS was used to determine the
      site of reorganization. The mechanisms involved were evaluated by measuring the
      thresholds for transcranial magnetic stimulation (TMS) and by testing
      intracortical inhibition and facilitation. With TMS, the threshold for muscle
      activation on the amputated side was lower than that of the intact side, but with
      transcranial electrical stimulation there was no difference in motor threshold
      between the two sides. TMS at the maximal output of the stimulator activated a
      higher percentage of the motor neuron pool (%MNP) on the amputated side than on
      the intact side. The %MNP activated by spinal electrical stimulation was similar
      on the two sides. Paired TMS study showed significantly less intracortical
      inhibition on the amputated side. Our findings suggest that motor reorganization
      after lower-limb amputation occurs predominately at the cortical level. The
      mechanisms involved are likely to include reduction of GABAergic inhibition.

PMID- 9547252
TI  - Response to change is facilitated by a three-neuron disinhibitory pathway in the
      tiger salamander retina.
AB  - Most retinal ganglion cells respond only transiently, for approximately 150 msec
      at the onset and termination of a light flash. The responses are transient
      because it has been shown that bipolar-to-ganglion cell transmission is truncated
      after 150 msec by a feedback inhibition to bipolar cell terminals. The feedback
      inhibition itself must be delayed by approximately 150 msec to allow the initial
      bipolar-ganglion cell transmission. This study identifies a three-component
      serial synaptic pathway from glycinergic amacrine cells to GABAergic amacrine
      cells to bipolar cell terminals as one source of this delay. We used perforated
      and whole-cell patch-clamp recordings to measure the timing of light responses in
      amacrine, bipolar, and ganglion cells under control and glycine and GABA receptor
      blocked conditions. Our results suggest that, after a light flash, a population
      of glycinergic amacrine cells responds first, inhibiting a population of
      GABAergic amacrine cells for approximately 150 msec. The GABAergic amacrine cells
      feed back to bipolar terminals, but only after the 150 msec delay, allowing the
      bipolar terminals to excite ganglion cells for the first 150 msec. Blocking the
      glycinergic amacrine cell activity with strychnine allows the GABAergic system to
      become active earlier. GABAergic amacrine cells then inhibit release from bipolar
      cells earlier. Under these conditions, the ganglion cell response to change would
      be decreased.

PMID- 9547253
TI  - Time-dependent reversal of long-term potentiation by an integrin antagonist.
AB  - The integrin antagonist Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) was applied by local
      ejection to one of two recording sites in hippocampal slices at various times
      before and after long-term potentiation (LTP) was induced at both sites with
      theta burst stimulation. Applications 10 min before, immediately after, and 10
      min after induction caused LTP at the experimental site to decay steadily
      relative to that at the within-slice control site. However, application at 25 min
      or more after induction had no detectable effect on potentiation. Similar results
      were obtained when the integrin antagonist was perfused into the slice rather
      than applied locally. The time period after induction during which GRGDSP
      interfered with LTP consolidation corresponds to that during which LTP is
      susceptible to reversal by low-frequency afferent stimulation and newly formed
      memories are vulnerable to various disruptive treatments. Comparable experiments
      using a peptide that blocks an extracellular binding site of neural cell adhesion
      molecules (NCAMs) did not yield time-dependent reversal of LTP; i.e., an
      antagonist that interacts with the fourth immunoglobulin-like domain reduced LTP
      when applied before induction but not afterward. Moreover, LTP formation occurred
      normally in the presence of an antibody against the fibronectin repeat domain of
      NCAM. These results suggest that integrin activation and signaling occurring over
      several minutes after LTP induction are necessary for stabilizing synaptic
      potentiation and by inference may be required for the conversion of new memories
      into a not readily disrupted state.

PMID- 9547254
TI  - Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene
      dosage, genetic background, and developmental adaptations.
AB  - Locomotor activity is a polygenic trait that varies widely among inbred strains
      of mice (). To characterize the role of D2 dopamine receptors in locomotion, we
      generated F2 hybrid (129/Sv x C57BL/6) D2 dopamine receptor (D2R)-deficient mice
      by gene targeting and investigated the contribution of genetic background to open
      field activity and rotarod performance. Horizontal activity of D2R-/- mice was
      approximately half that of drug-naive, strain-matched controls but was
      significantly greater than haloperidol-treated controls, which were markedly
      hypokinetic. Wild-type 129/SvEv and C57BL/6 mice with functional D2 receptors had
      greater interstrain differences in spontaneous activity than those among the F2
      hybrid mutants. Incipient congenic strains of D2R-deficient mice demonstrated an
      orderly gene dosage reduction in locomotion superimposed on both extremes of
      parental background locomotor activity. In contrast, F2 hybrid D2R-/- mice had
      impaired motor coordination on the rotarod that was corrected in the congenic
      C57BL/6 background. Wild-type 129/SvEv mice had the poorest rotarod ability of
      all groups tested, suggesting that linked substrain 129 alleles, not the absence
      of D2 receptors per se, were largely responsible for the reduced function of the
      F2 hybrid D2R-/- and D2R+/- mice. Neurochemical and pharmacological studies
      revealed unexpectedly normal tissue striatal monoamine levels and no evidence for
      supersensitive D1, D3, or D4 dopamine receptors in the D2R-/- mice. However,
      after acute monoamine depletion, akinetic D2R+/- mice had a significantly greater
      synergistic restoration of locomotion in response to SKF38393 and quinpirole
      compared with any group of D2R+/+ controls. We conclude that D2R-deficient mice
      are not a model of Parkinson's disease. Our studies highlight the interaction of
      multiple genetic factors in the analysis of complex behaviors in gene knock-out
      mice.

PMID- 9547255
TI  - Phosphorylation of mitogen-activated protein kinase by one-trial and multi-trial
      classical conditioning.
AB  - The pathway supporting the conditioned stimulus (CS) is one site of plasticity
      that has been studied extensively in conditioned Hermissenda. Several signal
      transduction pathways have been implicated in classical conditioning of this
      preparation, although the major emphasis has been on protein kinase C. Here we
      provide evidence for the activation and phosphorylation of a mitogen-activated
      protein kinase (MAPK) pathway by one-trial and multi-trial conditioning. A one
      trial in vitro conditioning procedure consisting of light (CS) paired with the
      application of 5-HT results in the increased incorporation of 32PO4 into proteins
      detected with two-dimensional gel electrophoresis. Two of the phosphoproteins
      have molecular weights of 44 and 42 kDa, consistent with extracellular signal
      regulated protein kinases (ERK1 and ERK2). Phosphorylation of the 44 and 42 kDa
      proteins by one-trial conditioning was inhibited by pretreatment with PD098059, A
      MEK1 (ERK-Activating kinase) inhibitor. Assays of ERK activity with brain myelin
      basic protein as a substrate revealed greater ERK activity for the group that
      received one-trial conditioning compared with an unpaired control group. Western
      blot analysis of phosphorylated ERK using antibodies recognizing the dually
      phosphorylated forms of ERK1 and ERK2 showed an increase in phosphorylation after
      one-trial conditioning compared with unpaired controls. The increased
      phosphorylation of ERK after one-trial conditioning was blocked by pretreatment
      with PD098059. Hermissenda that received 10 or 15 conditioning trials showed
      significant behavioral suppression compared with pseudo-random controls. After
      conditioning and behavioral testing, the conditioned animals showed significantly
      greater phosphorylation of ERK compared with the pseudo-random controls. These
      results show that the ERK-MAPK signaling pathway is activated in Pavlovian
      conditioning of Hermissenda.

PMID- 9547256
TI  - The D arm of tRNATyr is necessary and sufficient for import into Leishmania
      mitochondria in vitro.
AB  - Transfer RNAs are selectively imported from the cytoplasm into mitochondria of
      kinetoplastid protozoa such as Leishmania . The specific structural features of
      tRNA which determine selectivity are largely unknown. Using an in organello
      system from Leishmania , the import signals on tRNATyrand on a synthetic
      transcript which binds to the same receptor, were studied by deletion and
      reconstruction analyses. In both cases, short oligoribonucleotides (minihelices)
      containing the sequence UGGYAGAG were imported with high efficiency in the
      presence of ATP. This motif is present in the D arm of tRNATyr, as well as in the
      majority of imported Leishmania tRNAs. Deletion of the D arm, or a point mutation
      in the conserved motif, reduces importability. The import signal coincides with
      the binding site for the mitochondrial receptor TAB. tRNAGln, which is not
      imported, forms non-productive, TAB-independent complexes with the mitochondrial
      surface. However, the observation that the imported:bound ratio of the D arm
      minihelix is higher than that of the entire molecule suggests that the post
      binding translocation step is constrained in terms of size or structural
      flexibility. Kinetic studies of minihelix import indicate stepwise insertion of
      the molecule into import channels.

PMID- 9547257
TI  - DNA topoisomerase II sites in the histone H4 gene during the highly synchronous
      cell cycle of Physarum polycephalum.
AB  - The nearly perfect synchrony of nuclear division in a plasmodium of Physarum
      polycephalum provides a powerful system to analyze topoisomerase II cleavage
      sites in the course of the cell cycle. The histone H4 locus, whose schedule of
      replication and transcription is precisely known, was chosen for this analysis.
      Drug-induced topoisomerase II sites are clustered downstream of the histone H4
      gene and appear highly dependent on cell cycle stage. They were only detected in
      mitosis and at the very beginning of S phase, precisely at the time of
      replication of the histone H4 region. The sites, which were absent in G2 phase,
      reappeared at the next mitosis. Remarkably, DNase I hypersensitive sites occurred
      in nearly the same location, but their schedule was totally different: they were
      absent in mitosis and present in G2. This schedule follows H4 transcription,
      which peaks in mid-S phase and in the second part of G2 phase and is off during
      mitosis. These results suggest that topoisomerase II may not be involved in
      transcription, but plays a role in remodeling chromatin structure, both during
      chromosome condensation in prophase/metaphase to allow their decatenation and
      during chromosome decondensation after metaphase to allow replication fork
      passage throughout the region.

PMID- 9547258
TI  - Accelerated mRNA decay in conditional mutants of yeast mRNA capping enzyme.
AB  - Current models of mRNA decay in yeast posit that 3' deadenylation precedes
      enzymatic removal of the 5' cap, which then exposes the naked end to 5'
      exonuclease action. Here, we analyzed gene expression in Saccharomyces cerevisiae
      cells bearing conditional mutations of Ceg1 (capping enzyme), a 52 kDa protein
      that transfers GMP from GTP to the 5' end of mRNA to form the GpppN cap
      structure. Shift of ceg1 mutants to restrictive temperature elicited a rapid
      decline in the rate of protein synthesis, which correlated with a sharp reduction
      in the steady-state levels of multiple individual mRNAs. ceg1 mutations prevented
      the accumulation of SSA1 and SSA4 mRNAs that were newly synthesized at the
      restrictive temperature. Uncapped poly(A)+ SSA4 mRNA accumulated in cells lacking
      the 5' exoribonuclease Xrn1. These findings provide genetic evidence for the long
      held idea that the cap guanylate is critical for mRNA stability. The
      deadenylation-decapping-degradation pathway appears to be short-circuited when
      Ceg1 is inactivated.

PMID- 9547259
TI  - Phosphorylation of tobacco eukaryotic translation initiation factor 4A upon
      pollen tube germination.
AB  - Eukaryotic translation initiation factor eIF-4A is a member of the DEAD box
      family of RNA helicases and RNA-dependent ATPases. In tobacco, eIF-4A is encoded
      by a gene family with one isoform, eIF-4A8, being exclusively expressed in
      pollen. This pollen-specific isoform is a candidate for mediating translational
      control in the developing gametophyte. Here we show that eIF-4A is barely
      phosphorylated in mature pollen, but during pollen tube germination, two isoforms
      of eIF-4A become phosphorylated. Phosphoamino acid analysis indicated
      phosphorylation of threonine. In order to determine whether pollen-specific eIF
      4A8 is among the phosphorylated isoforms, we raised transgenic tobacco plants
      overexpressing eIF-4A8 containing a histidine tag. Hereby, we could show that
      indeed eIF-4A8 is modified through phosphorylation. The biological relevance of
      the phosphorylation of eIF-4A is discussed.

PMID- 9547260
TI  - Cloning and characterization of a human DEAH-box RNA helicase, a functional
      homolog of fission yeast Cdc28/Prp8.
AB  - During the splicing process, spliceosomal snRNAs undergo numerous conformational
      rearrangements that appear to be catalyzed by proteins belonging to the DEAD/H
      box superfamily of RNA helicases. We have cloned a new RNA helicase gene,
      designated DBP2 (DEAH-boxprotein), homologous to the Schizosaccaromyces pombe
      cdc28(+)/prp8(+) gene involved in pre-mRNA splicing and cell cycle progression.
      The full-length DBP2 contains 3400 nucleotides and codes for a protein of 1041
      amino acids with a calculated mol. wt of 119 037 Da. Transfection experiments
      demonstrated that the GFP-DBP2 gene product, transiently expressed in HeLa cells,
      was localized in the nucleus. The DBP2 gene was mapped by FISH to the MHC region
      on human chromosome 6p21.3, a region where many malignant, genetic and autoimmune
      disease genes are linked. Because the expression of DBP2 gene in S.pombe prp8
      mutant cells partially rescued the temperature-sensitive phenotype, we conclude
      that DBP2 is a functional human homolog of the fission yeast Cdc28/Prp8 protein.

PMID- 9547261
TI  - The pro-oligonucleotide approach: solid phase synthesis and preliminary
      evaluation of model pro-dodecathymidylates.
AB  - A modified phosphoramidite method has been designed for the solid-phase synthesis
      of two dodecathymidine phosphotriesters and two dodecathymidine
      thionophosphotriesters. In these analogs, each internucleoside link bears an S 
      acyl-2-thioethyl (Me-SATE or tBu-SATE) group removable upon esterase activation.
      Efficient synthesis of these lipophilic analogs was achieved thanks to the use of
      a photolabile linker anchored to the solid support in combination with thymidine
      3'- O -phosphoramidites having a SATE group in place of the regular 2-cyanoethyl
      one. Both dodecathymidine phosphotriester and thionophosphotriester having S 
      acetyl-2-thioethyl groups were found to be stable in the presence of snake venom
      and calf spleen phosphodiesterases whereas, upon incubation in CEM cell extracts,
      they were selectively hydrolyzed to the anionic parent dodecathymidylate and
      dodecathymidine phosphorothioate, respectively. In addition, Me-SATE-protected
      dodecathymidine thionophosphotriester was stable in mouse and human sera as well
      as in human gastric juice. These results depict the potential of SATE-protected
      oligonucleotides as prodrugs of antisense oligonucleotides.

PMID- 9547262
TI  - Transcription activation by Escherichia coli FNR protein: similarities to, and
      differences from, the CRP paradigm.
AB  - During transcription activation at FNR-dependent promoters where the DNA site for
      FNR overlaps the -35 element, a surface-exposed activating region in the upstream
      subunit of the FNR dimer interacts with the C-terminal domain of the RNA
      polymerase alpha subunit. Starting with a cloned fnr gene encoding a defective
      FNR derivative carrying substitutions in this activating region, we screened a
      library of random mutations to identify substitutions that restored FNR activity.
      Activity can be restored by substitutions at residues T118, E47 and K60. The
      locations of these residues identify three separate surface-exposed regions of
      FNR that can play a role in transcription activation. These three regions appear
      to be analogues of Activating Region 1, Activating Region 2 and Activating Region
      3 of the cyclic AMP receptor protein, CRP: our results underscore the
      similarities between FNR and CRP.

PMID- 9547263
TI  - Improving stable transfection efficiency: antioxidants dramatically improve the
      outgrowth of clones under dominant marker selection.
AB  - Many cell lines are sensitive to growth at low cell density and undergo apoptosis
      induced by oxidative stress if the cell density is decreased below a critical
      threshold. In stable transfection experiments this cell density-dependent growth
      may be the limiting factor, since during drug selection the cell density falls
      below the critical threshold, precluding outgrowth of transfected clones. We
      describe here a simple protocol for the establishment of stably transfected human
      B cell lines making use of the protective action of antioxidants. The protocol
      includes: (i) seeding the cells in medium supplemented with sodium pyruvate,
      alpha-thioglycerol and bathocuproine disulfonate; (ii) delaying the onset of
      dominant marker selection to improve recovery of the cells after electroporation.
      Stably transfected clones have thus been obtained from Burkitt's lymphoma lines,
      which have been regarded as untransfectable. Using this protocol the stable
      transfection efficiency with episomal plasmids approaches the transient
      transfection efficiency, indicating that virtually every transfected cell can be
      established as a stably transfected clone. This protocol should also prove useful
      for other cell lines, e.g. neuronal cells, having similar sensitivities to
      oxidative stress.

PMID- 9547264
TI  - (1,4,7-trimethyl-1,4,7-triazacyclononane)iron (III)-mediated cleavage of DNA:
      detection of selected protein-DNA interactions.
AB  - A new reagent for the oxidative cleavage of DNA, (1,4,7-trimethyl-1, 4,7
      triazacyclononane)iron(III) chloride was recently introduced. We have determined
      the utility of this reagent for detecting protein-DNA interactions within two
      types of complexes. Interestingly, we find that the rates of DNA cleavage by this
      reagent are differentially affected by the two classes of protein-DNA interactons
      studied. We find that the rate of DNA cleavage by this reagent is relatively
      unaffected by the non-sequence-specific histone-DNA interactions within a
      nucleosome complex. Conversely, a clear footprint pattern is obtained with two
      different DNA sequence-specific protein-DNA complexes. The results suggest that
      (1,4,7-trimethyl-1,4,7-triazacyclononane)iron(III) chloride will be a useful
      reagent to probe trans -acting-factor-DNA interactions within a chromatin
      environment. Differences between these two types of protein-DNA interactions,
      which might account for this observation, are discussed.

PMID- 9547265
TI  - Short unligated sticky ends enable the observation of circularised DNA by atomic
      force and electron microscopies.
AB  - A comparative study of the stabilisation of DNA sticky ends by divalent cations
      was carried out by atomic force microscopy (AFM), electron microscopy and agarose
      gel electrophoresis. At room temperature, molecules bearing such extremities are
      immediately oligomerised or circularised by addition of Mg2+or Ca2+. This
      phenomenon, more clearly detected by AFM, requires the presence of uranyl salt,
      which stabilises the structures induced by Mg2+or Ca2+. DNA fragments were
      obtained by restriction enzymes producing sticky ends of 2 or 4 nucleotides (nt)
      in length with different guanine plus cytosine (GC) contents. The stability of
      the pairing is high when ends of 4 nt display a 100% GC-content. In that case,
      95% of DNA fragments are maintained circular by the divalent cations, although 2
      nt GC-sticky ends are sufficient for a stable pairing. DNA fragments with one
      blunt end and the other sticky appear as dimers in the presence of Mg2+.
      Dimerisation was analysed by varying the lengths and concentrations of DNA
      fragments, the base composition of the sticky ends, and also the temperature. Our
      observation provides a new powerful tool for construction of inverted dimers, and
      circularisation, ligation analysis or short bases sequence interaction studies.

PMID- 9547266
TI  - The activation function 2 domain of hepatic nuclear factor 4 is regulated by a
      short C-terminal proline-rich repressor domain.
AB  - Hepatic nuclear factor 4 (HNF4) is a transcription factor whose expression is
      crucial for mouse embryonic development, for liver-specific gene expression and
      for the prevention of one form of maturity-onset diabetes of the young. Its
      domain structure has been defined previously and is similar to other members of
      the nuclear receptor superfamily. A repressor domain has now been localised to a
      region of 14 amino acids (residues 428-441) near the C-terminus of HNF4 and is
      sufficient by itself to repress the activity of the activation function 2 (AF2)
      domain. Multiple mutations within this repressor domain enhance activity.
      Interestingly, this repressor domain shares homology with a repressor domain in
      the progesterone receptor. In a detailed mutagenesis study of the AF2 core, we
      demonstrate that L 366, which is conserved in the AF2 core between HNF4 and a
      number of orphan nuclear receptors, is essential for the full activity of the AF2
      domain. Furthermore, a double mutation of E 363 and L 366 suggests that these
      residues might act in a cooperative manner.

PMID- 9547267
TI  - Synthesis and RNA polymerase incorporation of the degenerate ribonucleotide
      analogue rPTP.
AB  - The synthesis and enzymatic incorporation into RNA of the hydrogen bond
      degenerate nucleoside analogue 6-(beta-d-ribofuranosyl)-3, 4-dihydro-8H
      pyrimido[4,5-c]-[1,2]oxazin-7-one (P) is described. The 5'-triphosphate of this
      analogue is readily incorporated by T3, T7 and SP6 RNA polymerases into RNA
      transcripts, being best incorporated in place of UTP, but also in place of CTP.
      When all the uridine residues in an HIV-1 TAR RNA transcript are replaced by P
      the transcript has similar characteristics to the wild-type TAR RNA, as
      demonstrated by similar melting temperatures and CD spectra. The P-substituted
      TAR transcript binds to the Tat peptide ADP-1 with only 4-fold lowered efficiency
      compared with wild-type TAR.

PMID- 9547269
TI  - Repressor titration: a novel system for selection and stable maintenance of
      recombinant plasmids.
AB  - The propagation of recombinant plasmids in bacterial hosts, particularly in
      Escherichia coli, is essential for the amplification and manipulation of cloned
      DNA and the production of recombinant proteins. The isolation of bacterial
      transformants and subsequent stable plasmid maintenance have traditionally been
      accomplished using plasmid-borne selectable marker genes. Here we describe a
      novel system that employs plasmid-mediated repressor titration to activate a
      chromosomal selectable marker, removing the requirement for a plasmid-borne
      marker gene. A modified E.coli host strain containing a conditionally essential
      chromosomal gene (kan) under the control of the lac operator/promoter, lac O/P,
      has been constructed. In the absence of an inducer (allolactose or IPTG) this
      strain, DH1 lackan , cannot grow on kanamycin-containing media due to the
      repression of kan expression by LacI protein binding to lac O/P. Transformation
      with a high copy-number plasmid containing the lac operator, lac O, effectively
      induces kan expression by titrating LacI from the operator. This strain thus
      allows the selection of plasmids without antibiotic resistance genes (they need
      only contain lac O and an origin of replication) which have clear advantages for
      use as gene therapy vectors. Regulation in the same way of an essential,
      endogenous bacterial gene will allow the production of recombinant therapeutics
      devoid of residual antibiotic contamination.

PMID- 9547268
TI  - TFIID (TBP) stabilizes the binding of MyoD to its DNA site at the promoter and
      MyoD facilitates the association of TFIIB with the preinitiation complex.
AB  - The myogenic determination factor MyoD activates the transcription of muscle
      specific genes by binding to consensus DNA sites found in the regulatory
      sequences of these genes. The interaction of MyoD with the basal transcription
      machinery is not known. Several activators induce transcription by recruiting
      TFIID and/or TFIIB to the promoter. We asked whether MyoD interacted functionally
      with TFIID and TFIIB in transcription. We reconstituted in vitro DNA binding and
      transcription systems of MyoD and basal transcription factors, and found that
      MyoD function in transcription occurred during the assembly of the preinitiation
      complex. Interestingly, MyoD activated transcription without affecting the
      binding of TFIID to the promoter. However, TFIID or TBP dramatically stabilized
      the binding of MyoD to its recognition site. MyoD and TBP interacted in solution.
      Deletion analysis of MyoD suggested that interaction of MyoD with TBP is needed
      for its activity in transcription. At a later stage of assembly, MyoD stabilized
      the binding of TFIIB to the preinitiation complex. These findings suggest that
      MyoD is involved in two steps of preinitiation; first, TFIID stabilizes MyoD
      binding to its DNA recognition site and at a later stage MyoD facilitates the
      association of TFIIB with the preinitiation complex.

PMID- 9547270
TI  - A stimulatory RNA associated with RecBCD enzyme.
AB  - RecBCD enzyme acts in the major pathway of homologous recombination of linear DNA
      in Escherichia coli. The enzyme unwinds DNA and is an ATP-dependent double-strand
      and single-strand exonuclease and a single-strand endonuclease; it acts at Chi
      recombination hotspots (5'-GCTGGTGG-3') to produce a recombinogenic single
      stranded DNA 3'-end. We found that a small RNA with a unique sequence of
      approximately 24 nt was tightly bound to RecBCD enzyme and co-purified with it.
      When added to native enzyme this RNA, but not four others, increased DNA
      unwinding and Chi nicking activities of the enzyme. In seven similarly active
      enzyme preparations the molar ratio of RNA molecules to RecBCD enzyme molecules
      ranged from 0.2 to <0.008. These results suggest that, although this unique RNA
      is not an essential enzyme subunit, it has a biological role in stimulating
      RecBCD enzyme activity.

PMID- 9547271
TI  - Structure and regulation of a polymorphic gene encoding folate receptor type
      gamma/gamma'.
AB  - The human folate receptor (hFR) type gamma and gamma' are constitutively secreted
      proteins that are expressed primarily in hematopoietic tissues and are potential
      serum markers for certain hematopoietic malignancies. hFR-gamma' is a variant of
      hFR-gamma with a two base deletion in its cDNA resulting in a truncated
      polypeptide. The gene encoding hFR-gamma' was isolated from a placental genomic
      library. The gene has five exons, four introns and a 5' flanking sequence which
      contains multiple putative regulatory elements. From RNase protection assay and
      RACE analysis, the major site of transcriptional initiation was identified at -56
      nt. Systematically deleted fragments in the 5' region of the genomic DNA of FR
      gamma' were ligated into the PGL3Basic plasmid and the reporter luciferase
      activity was assayed in cell lysates from transiently transfected NIH3T3 cells.
      From those results, putative positive and negative regulatory regions in the 5'
      flanking sequences were noted, and a TATA-less proximal promoter was located
      between -206 and -22 nt. Gel mobility shift and supershift analyses as well as
      mutagenesis experiments revealed that Sp1 and ets binding elements in the
      proximal promoter region confer transcriptional activity. From partial sequencing
      of genomic DNA, genomic Southern blots, RACE analysis and RNase protection
      assays, it appears that hFR-gamma shares the gene organization of hFR-gamma'. The
      results of the analysis of genomic DNA in spleen tissues from several
      individuals, were consistent with the interpretation that hFR-gamma and hFR
      gamma' are encoded by a polymorphic gene.

PMID- 9547272
TI  - DNA binding properties of a chemically synthesized DNA binding domain of hRFX1.
AB  - The RFX DNA binding domain (DBD) is a novel highly conserved motif belonging to a
      large number of dimeric DNA binding proteins which have diverse regulatory
      functions in eukaryotic organisms, ranging from yeasts to human. To characterize
      this novel motif, solid phase synthesis of a 76mer polypeptide corresponding to
      the DBD of human hRFX1 (hRFX1/DBD), a prototypical member of the RFX family, has
      been optimized to yield large quantities (approximately 90 mg) of pure compound.
      Preliminary two-dimensional1H NMR experiments suggested the presence of helical
      regions in this sequence in agreement with previously reported secondary
      structure predictions. In gel mobility shift assays, this synthetic peptide was
      shown to bind in a cooperative manner the 23mer duplex oligodeoxynucleotide
      corresponding to the binding site of hRFX1, with a 2:1 stoichoimetry due to an
      inverse repeat present in the 23mer. The stoichiometry of this complex was
      reduced to 1:1 by decreasing the length of the DNA sequence to a 13mer
      oligonucleotide containing a single half-site. Surface plasmon resonance
      measurements were achieved using this 5'-biotylinated 13mer oligonucleotide
      immobilized on an avidin-coated sensor chip. Using this method an association
      constant (K a = 4 x 10(5)/M/s), a dissociation constant (K d = 6 x 10(-2)/s) and
      an equilibrium dissociation constant (K D = 153 nM) were determined for binding
      of hRFX1/DBD to the double-stranded 13mer oligonucleotide. In the presence of
      hRFX1/DBD the melting temperature of the 13mer DNA was increased by 16 degreesC,
      illustrating stabilization of the double-stranded conformation induced by the
      peptide.

PMID- 9547273
TI  - Molecular beacon probes combined with amplification by NASBA enable homogeneous,
      real-time detection of RNA.
AB  - Molecular beacon probes can be employed in a NASBA amplicon detection system to
      generate a specific fluorescent signal concomitantly with amplification. A
      molecular beacon, designed to hybridize within the target sequence, was
      introduced into NASBA reactions that amplify the genomic RNA of potato leafroll
      virus (PLRV). During amplification, the probe anneals to the antisense RNA
      amplicon generated by NASBA, producing a specific fluorescent signal that can be
      monitored in real-time. The assay is rapid, sensitive and specific. As RNA
      amplification and detection can be carried out in unopened vessels, it minimizes
      the risk of carry-over contaminations. Robustness has been verified on real-world
      samples. This homogeneous assay, called AmpliDet RNA, is a significant
      improvement over current detection methods for NASBA amplicons and is suitable
      for one-tube applications ranging from high-throughput diagnostics to in vivo
      studies of biological activities.

PMID- 9547274
TI  - The importance of base pairing in the penultimate stem of Escherichia coli 16S
      rRNA for ribosomal subunit association.
AB  - The influence of base pairing in the penultimate stem of Escherichia coli 16S
      rRNA (defined as nt 1409-1491) on ribosome function has been addressed by the
      construction of mutations in this region of rRNA. Two sets of mutations were made
      on either side of a structurally conserved region in the penultimate stem that
      disrupted base pairing, while a third set of mutations replaced the wild-type
      sequence with other base pair combinations. The effects of these mutations were
      analyzed in vivo and in vitro . The mutations that disrupted base pairing caused
      significant increases in cell doubling times as well as a severe subunit
      association defect and a modest increase in frame shifting and stop codon read
      through. Restoration of base pairing restored wild-type growth rates, decoding
      and subunit association, indicating that base pairing in this region is essential
      for proper ribosome function.

PMID- 9547275
TI  - Characterisation of Leishmania telomeres reveals unusual telomeric repeats and
      conserved telomere-associated sequence.
AB  - Characterisation of the telomeres of Leishmania is important for understanding
      many aspects of the parasitic life of this primitive protozoan and for the
      completion of the physical map and sequencing of the genome. After sequencing
      more than 300 telomere-derived clones from Leishmania braziliensis and Leishmania
      major, a conserved 100 bp sequence was identified immediately adjacent to the
      telomere at the chromosome end and was named LCTAS (Leishmania conserved telomere
      associated sequence). The LCTAS contains two conserved sequence boxes, and is
      present in all Leishmania species studied. The organisation of the LCTAS in the
      telomeric region differs between L. braziliensis and L. major: in L. major the
      LCTASs are tandemly repeated, while in L. braziliensis the LCTAS is present as a
      single copy per end. Two additional TASs with 1.6 kb and 274 bp repeat
      structures, which are apparently different to LCTAS, were isolated and mapped
      onto a L. braziliensis 250 kb multicopy minichromosome and the L. major
      chromosome 1, respectively. An unusual feature in L. braziliensis is that the
      telomeric repeats are often comprised of a novel tandem repeat CCCTAACCCGTGGA. A
      'slippage' mechanism for LCTAS formation is proposed in this study as an
      alternative way for the synthesis and maintenance of telomeres and subtelomere
      regions.

PMID- 9547276
TI  - Coexistence of nuclear DNA-encoded tRNAVal(AAC) and mitochondrial DNA-encoded
      tRNAVal(UAC) in mitochondria of a liverwort Marchantia polymorpha.
AB  - The liverwort Marchantia polymorpha mitochondrial DNA encodes almost all tRNAs
      required for mitochondrial translation except for the isoleucine (AUU, AUC) and
      threonine (ACA, ACG) codons, while the missing tRNAs are supplied in part by the
      nucleus and imported in mitochondria. In this paper, we report a finding of two
      radically different nuclear tRNAVal(AAC) genes and import of the corresponding
      tRNA isoacceptors in M.polymorpha mitochondria. This finding is surprising since
      the mtDNA encodes the gene for tRNAVal(UAC), which alone was considered
      sufficient for translating all four valine codons GUN by the U/N wobble
      mechanism. The present results suggest for the first time that the import of
      ncDNA-encoded tRNAs may result in decoding overlaps in plant mitochondria. The
      coexistence of nuclear DNA-encoded tRNAVal(AAC) and mitochondrial DNA-encoded
      tRNAVal(UAC) in liverwort mitochondria and the significance for the decoding
      mechanism as well as evolution of tRNA import are discussed.

PMID- 9547277
TI  - STAT 5 and NF-Y are involved in expression and growth hormone-mediated sexually
      dimorphic regulation of cytochrome P450 3A10/lithocholic acid 6beta-hydroxylase.
AB  - The level of expression of a number of sexually differentiated liver proteins is
      primarily determined by plasma growth hormone (GH). Adult males have a pulsatile
      profile of GH release, while females have a relatively steady-state pattern of GH
      release. An important subset of these sexually differentiated hepatic proteins is
      certain cytochrome P450s (P450s). CYP3A10/6beta-hydroxylase is a male-specific
      P450 that catalyzes 6beta-hydroxylation of lithocholic acid, and the pattern of
      GH secretion is directly responsible for male-specific expression of this gene.
      The DNA element involved in GH-mediated regulation of CYP3A10/6beta-hydroxylase
      promoter activity binds a member of the STAT (signal transducers and activators
      of transcription) family of proteins. In this study we functionally demonstrate
      that two members of the STAT family, STAT 5a and STAT 5b, mediate GH-dependent
      regulation of CYP3A10/6beta-hydroxylase promoter activity. Furthermore, a
      neighboring DNA element binds NF-Y, a transcription factor involved in
      maintaining high levels of transcription of many genes and known to functionally
      interact with other factors. In the CYP3A10/6beta-hydroxylase gene, NF-Y also
      modulates binding of STAT 5, thereby modulating GH-mediated activation of its
      transcription.

PMID- 9547278
TI  - Triple helices formed at oligopyrimidine*oligopurine sequences with base pair
      inversions: effect of a triplex-specific ligand on stability and selectivity.
AB  - Oligonucleotide-directed triple helix formation is mostly restricted to
      oligopyrimidine*oligopurine sequences of double helical DNA. An interruption of
      one or two pyrimidines in the oligopurine target strand leads to a strong triplex
      destabilisation. We have investigated the effect of nucleotide analogues
      introduced in the third strand at the site opposite the base pair inversion(s).
      We show that a 3-nitropyrrole derivative (M) discriminates G*C from C*G, A*T and
      T*A in the presence of a triplex-specific ligand (a benzo[e]pyridoindole
      derivative, BePI). N6-methoxy-2,6-diaminopurine (K) binds to an A*T base pair
      better than a T*A, G*C or C*G base pair. Some discrimination is still observed in
      the presence of BePI and triplex stability is markedly increased. These findings
      should help in designing BePI-oligonucleotide conjugates to extend the range of
      DNA sequences available for triplex formation.

PMID- 9547280
TI  - Involvement of the 5'-untranslated region in cold-regulated expression of the
      rbpA1 gene in the cyanobacterium Anabaena variabilis M3.
AB  - Transcript of the rbpA1 gene in Anabaena variabilis accumulates significantly at
      low growth temperatures below 28 degreesC. This accumulation was maximal at 16
      degreesC. Accumulation of the rbpA1 transcript was completely abolished by
      rifampicin, but not by chloramphenicol. Photosynthesis was not required for this
      cold-induced accumulation. This accumulation of transcript was partly accounted
      for by increased stability of the rbpA1 transcript at low temperature. Expression
      of chimeric genes containing 3'-deleted rbpA1 sequences fused to the lacZ gene
      was regulated by low temperature when almost the entire 5'-untranslated region
      (5'-UTR) remained undeleted. Further deletion resulted in constitutive expression
      of the chimeric gene. The 5'-UTR sequence formed two types of complexes in vitro
      with protein extract from cells grown at 38 degreesC, but not with extract from
      the 22 degreesC grown cells. Affinity purification identified polypeptides of 75
      and 32 kDa in Complex 1 and a 72 kDa polypeptide in Complex 2. These results are
      compatible with a model in which expression of the rbpA1 gene is regulated by
      transcriptional derepression at low temperature, although additional mechanisms,
      such as regulation of mRNA stability, might also contribute to temperature
      dependent regulation.

PMID- 9547279
TI  - Efficient in vitro repair of 7-hydro-8-oxodeoxyguanosine by human cell extracts:
      involvement of multiple pathways.
AB  - To investigate the repair of oxidative damage in DNA, we have established an in
      vitro assay utilizing human lymphoblastoid whole cell extracts and plasmid DNA
      damaged by exposure to methylene blue and visible light. This treatment has been
      shown to produce predominantly 7-hydro-8-oxodeoxyguanosine (8-oxodG) in double
      stranded DNA at low levels of modification. DNA containing 1. 6 lesions per
      plasmid is substrate for efficient repair synthesis by cell extracts. The
      incorporation of dGMP is 2.7 +/- 0.5 times greater than the incorporation of
      dCMP, indicating an average repair patch of 3-4 nucleotides. Damage-specific
      nicking occurs within 15 min, while resynthesis is slower. The incorporation of
      dGMP increases linearly, while the incorporation of dCMP exhibits a distinct lag.
      Extracts from xeroderma pigmentosum (XP) complementation groups A and B exhibit
      25 and 40%, respectively, of the incorporation of dCMP compared with normal
      extracts, but extracts from an XP-D cell line exhibit twice the activity. These
      data suggest that the efficient repair of 8-oxodG lesions observed in human cell
      extracts involves more than one pathway of base excision repair.

PMID- 9547281
TI  - Structure-function analysis of the trypanosomatid spliced leader RNA.
AB  - In trypanosomes, all mRNAs possess a spliced leader (SL) at their 5' end. SL is
      added to pre-mRNA via trans -splicing from a small RNA, the SL RNA. To examine
      structure-function aspects of the trypanosomatid SL RNA, an in vivo system was
      developed in the monogenetic trypanosomatid Leptomonas collosoma to analyze the
      function of chimeric and site-directed SL RNA mutants in trans -splicing. Stable
      cell lines expressing chimeric and mutated SL RNA from the authentic SL RNA
      regulatory unit were obtained. The chimeric RNA was expressed and assembled into
      an SL RNP particle, but could not serve as a substrate in splicing. Mutations in
      loop II and III of L.collosoma SL RNA formed the Y structure intermediate. In
      addition, a double SL RNA mutant in loop II, and positions 7 and 8 of the intron,
      also formed the Y structure intermediate, suggesting that these intron positions,
      although proposed to participate in the interaction of SL RNA with U5, may not be
      crucial for the first step of the trans -splicing reaction. A mutation in the
      exon located in loop I was not utilized in splicing, suggesting the importance of
      exon sequences for trans -splicing in trypanosomes. However, a double SL RNA
      mutant in loop II and exon position 31 was utilized in both steps of splicing;
      the mutant thus provides a model molecule for further analysis of positions
      essential for the function of the SL RNA.

PMID- 9547282
TI  - Exploratory studies on azole carboxamides as nucleobase analogs: thermal
      denaturation studies on oligodeoxyribonucleotide duplexes containing pyrrole-3
      carboxamide.
AB  - In order to study base pairing properties of the amide group in DNA duplexes, a
      nucleoside analog, 1-(2'-deoxy-beta-D-ribofuranosyl)pyrrole-3-carboxamide, was
      synthesized by a new route from the ester, methyl 1-(2'-deoxy-3',5'-di-O-p 
      toluoyl-beta-D-erythro-pentofuranosyl)pyrrole-3-carboxylate, obtained from the
      coupling reaction between 1-chloro-2-deoxy-3,5-di-O -toluoyl-d
      erythropentofuranose and methyl pyrrole-3-carboxylate by treatment with
      dimethylaluminum amide. 1-(2'-Deoxy-beta-D-ribofuranosyl)pyrrole-3-carboxamide
      was incorporated into a series of oligodeoxyribonucleotides by solid-phase
      phosphoramidite technology. The corresponding oligodeoxyribonucleotides with 3
      nitropyrrole in the same position in the sequence were synthesized for UV
      comparison of helix-coil transitions. The thermal melting studies indicate that
      pyrrole-3-carboxamide, which could conceptually adopt either a dA-like or a dI
      like hydrogen bond conformation, pairs with significantly higher affinity to T
      than to dC. Pyrrole-3-carboxamide further resembles dA in the relative order of
      its base pairing preferences (T >dG >dA >dC). Theoretical calculations on the
      model compound N-methylpyrrole-3-carboxamide using density functional theory show
      little difference in the preference for a syntau versus anti conformation about
      the bond from pyrrole C3 to the amide carbonyl. The amide groups in both the
      minimized antitau and syntau conformations are twisted out of the plane of the
      pyrrole ring by 6-14 degrees. This twist may be one source of destabilization
      when the amide group is placed in the helix. Another contribution to the
      difference in stability between the base pairs of pyrrole-3-carboxamide with T
      and pyrrole-3-carboxamide with C may be the presence of a hydrogen bond in the
      former involving an acidic proton (N3-H of T).

PMID- 9547283
TI  - Comparative gene expression profiling by oligonucleotide fingerprinting.
AB  - The use of hybridisation of synthetic oligonucleotides to cDNAs under high
      stringency to characterise gene sequences has been demonstrated by a number of
      groups. We have used two cDNA libraries of 9 and 12 day mouse embryos (24 133 and
      34 783 clones respectively) in a pilot study to characterise expressed genes by
      hybridisation with 110 hybridisation probes. We have identified 33 369 clusters
      of cDNA clones, that ranged in representation from 1 to 487 copies (0.7%). 737
      were assigned to known rodent genes, and a further 13 845 showed significant
      homologies. A total of 404 clusters were identified as significantly
      differentially represented (P < 0.01) between the two cDNA libraries. This study
      demonstrates the utility of the fingerprinting approach for the generation of
      comparative gene expression profiles through the analysis of cDNAs derived from
      different biological materials.

PMID- 9547284
TI  - Advantages of 2'-O-methyl oligoribonucleotide probes for detecting RNA targets.
AB  - We have compared various kinetic and melting properties of oligoribonucleotide
      probes containing 2'-O-methylnucleotides or 2'-deoxynucleotides with regard to
      their use in assays for the detection of nucleic acid targets. 2'-O-Methyl
      oligoribonucleotide probes bound to RNA targets faster and with much higher
      melting temperatures (Tm values) than corresponding 2'-deoxy oligoribonucleotide
      probes at all lengths tested (8-26 bases). Tm values of both probes increased
      with length up to approximately 19 bases, with maximal differences in Tm between
      2'-O-methyl and 2'-deoxy oligoribonucleotide probes observed at lengths of 16
      bases or less. In contrast to RNA targets, 2'-O-methyl oligoribonucleotide probes
      bound more slowly and with the same Tm to DNA targets as corresponding 2'-deoxy
      oligoribonucleotide probes. Because of their greatly enhanced Tm when bound to
      RNA, 2'-O-methyl oligoribonucleotide probes can efficiently bind to double
      stranded regions of structured RNA molecules. A 17 base 2'-O-methyl
      oligoribonucleotide probe was able to bind a double-stranded region of rRNA
      whereas the same 17 base 2'- deoxy oligoribonucleotide probe did not. Due to
      their enhanced Tm when bound to RNA targets, shorter 2'-O-methyl
      oligoribonucleotide probes can be used in assays in place of longer 2'-deoxy
      oligoribonucleotide probes, resulting in enhanced discrimination between matched
      and mismatched RNA targets. A 12 base 2'-O-methyl oligoribonucleotide probe had
      the same Tm as a 19 base 2'-deoxy oligoribonucleotide probe when bound to a
      matched RNA target but exhibited a much larger decrease in Tm than the 2'-deoxy
      oligoribonucleotide probe when bound to an RNA target containing either 1 or 2
      mismatched bases. The increased Tm, faster kinetics of hybridization, ability to
      bind to structured targets and increased specificity of 2'-O-methyl
      oligoribonucleotide probes render them superior to corresponding 2'-deoxy
      oligoribonucleotides for use in assays that detect RNA targets.

PMID- 9547285
TI  - Using neural networks for prediction of the subcellular location of proteins.
AB  - Neural networks have been trained to predict the subcellular location of proteins
      in prokaryotic or eukaryotic cells from their amino acid composition. For three
      possible subcellular locations in prokaryotic organisms a prediction accuracy of
      81% can be achieved. Assigning a reliability index, 33% of the predictions can be
      made with an accuracy of 91%. For eukaryotic proteins (excluding plant sequences)
      an overall prediction accuracy of 66% for four locations was achieved, with 33%
      of the sequences being predicted with an accuracy of 82% or better. With the
      subcellular location restricting a protein's possible function, this method
      should be a useful tool for the systematic analysis of genome data and is
      available via a server on the world wide web.

PMID- 9547286
TI  - The effect of two antipodal fluorine-induced sugar puckers on the conformation
      and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2.
AB  - UV thermal melting studies, CD and NMR spectroscopies were employed to assess the
      contribution of antipodal sugar conformations on the stability of the canonical B
      DNA conformation of the Dickerson-Drew dodecamer duplex [[d(CGCGAATTCGCG)]2, (ODN
      1)]. Different oligodeoxynucleotide versions of ODN 1 were synthesized with
      modified thymidine units favoring distinct sugar conformations by using a 3'-
      endo (north) 2'-fluoro-2'-deoxyribofuranosyl thymine (1) or a 2'- endo (south) 2'
      fluoro-2'-deoxyarabinofuranosyl thymine (2). The results showed that two south
      thymidines greatly stabilized the double helix, whereas two north thymidines
      destabilized it by inducing a more A-like conformation in the middle of the
      duplex. Use of combinations of north and south thymidine conformers in the same
      oligo destabilized the double helix even further, but without inducing a
      conformational change. The critical length for establishing a detectable A-like
      conformation in the middle of a B-DNA ODN appears to be 4 bp. Our results suggest
      that manipulation of the conformation of DNA in a sequence-independent manner is
      possible.

PMID- 9547287
TI  - Transverse formamide gradients as a simple and easy way to optimise DNA single
      strand conformation polymorphism analysis.
AB  - Although widely used, the detection of DNA mutations by the single-strand
      conformation polymorphism (SSCP) method is often hampered by the need to examine
      a large set of electrophoretic conditions in order to select the one suited to
      the DNA sequence under study. We show here that the use of transverse chemical
      gradient gels allows for a quick and easy optimisation of SSCP analysis, as
      exemplified on two mutations in exon 2 of the alpha-1-antitrypsin gene.

PMID- 9547288
TI  - Gel electrophoretic detection of 7,8-dihydro-8-oxoguanine and 7, 8-dihydro-8
      oxoadenine via oxidation by Ir (IV).
AB  - Two gel electrophoretic methods are described for detection of 7, 8-dihydro-8
      oxoguanine and 7,8-dihydro-8-oxoadenine based on their further oxidation with one
      electron oxidants including IrCl62-and IrBr62-. The products of nucleobase
      oxidation lead to enhanced piperidine-sensitive cleavage and to highly visible
      stop points in a primer extension assay. 8-oxoG and 8-oxoA lesions may be
      distinguished by the latter's inability to be oxidized by IrBr62-compared to
      IrCl62-Comparison is also made to oxidation by MnO4-.

PMID- 9547289
TI  - Highly sensitive detection of gene expression of an intronless gene:
      amplification of mRNA, but not genomic DNA by nucleic acid sequence based
      amplification (NASBA).
AB  - NASBA is an isothermal nucleic acid amplification reaction that amplifies mRNA in
      a dsDNA background. Although similar to the sensitive reverse
      transcription/polymerase chain reaction (RT-PCR) in mRNA detection, NASBA is not
      prone to give false positive results caused by genomic dsDNA. Therefore, NASBA is
      unique for sensitive detection of transcription of intronless genes, which
      preclude strategies such as intron spanning primer pairs to control false
      positive results in RT-PCR. Using NASBA, mRNA of the intronless human interferon
      beta gene was demonstrated with a sensitivity of 10 copies, whereas 100 ng
      genomic DNA gave a negative result.

PMID- 9547290
TI  - A recombination based method to rapidly assess specificity of two-hybrid clones
      in yeast.
AB  - The yeast two-hybrid system is frequently used to identify protein-protein
      interactions. Confirming the specificity of candidate clones requires separation
      and isolation of yeast plasmids, propagation in bacteria and testing combinations
      of DNA-binding and activation domain hybrids in yeast. In order to simplify this
      procedure, we developed a rapid method based on PCR amplification of library
      insert DNAs and in vivo cloning into the activation domain hybrid vector.
      Reporter gene activity is assayed in parallel for combinations with different DNA
      binding domain hybrids. Further characterization of inserts does not require
      plasmid isolation and intermediate hosts.

PMID- 9547292
TI  - Translocation of microtubules caused by the alphabeta, beta and gamma outer arm
      dynein subparticles of Chlamydomonas.
AB  - Three kinds of subparticles of Chlamydomonas outer-arm dynein containing the
      alphabeta, beta and gamma heavy chains were isolated and assayed for their
      activities to translocate microtubules in vitro. All of them had activities to
      form bundles of microtubules in solution in an ATP-dependent manner and, when
      adsorbed on an appropriate glass surface, translocated microtubules. The
      alphabeta subparticle readily translocated microtubules on a silicone-coated
      glass surface with a velocity of 4.6 micron/second at 1 mM ATP. The beta
      subparticle translocated microtubules after it had been preincubated with tubulin
      dimer and when the Brownian movement of microtubules was suppressed by addition
      of methylcellulose. The velocity was on average 0.7 micron/second. The gamma
      subparticle translocated microtubules after being preincubated with tubulin dimer
      and adsorbed onto a silicone-coated glass surface. The velocity was about 3.8
      micron/second. The tubulin dimer appeared to facilitate in vitro motility by
      blocking the ATP-insensitive binding of dynein subparticles to microtubule. The
      alphabeta, beta and gamma subparticles were thus found to have different
      properties as motor proteins. In addition, these subparticles showed different
      dependencies upon the potassium acetate concentration. Hence the outer-arm dynein
      of Chlamydomonas is a complex of motor proteins with different properties.

PMID- 9547291
TI  - Cell cycle-associated accumulation of tissue inhibitor of metalloproteinases-1
      (TIMP-1) in the nuclei of human gingival fibroblasts.
AB  - We first confirmed an earlier immunohistochemical study showing that
      immunoreactive TIMP-1-like protein accumulated in the nuclei of human gingival
      fibroblasts (Gin-1 cells), reaching a maximum in the S phase of the cell cycle
      (Li, H., Nishio, K., Yamashita, K., Hayakawa, T. and Hoshino, T. (1995). Nagoya
      J. Med. Sci. 58, 133-142). Then we isolated this protein from a nuclear extract
      of Gin-1 cells and demonstrated it to be identical to human recombinant TIMP-1 by
      western blotting, by a sandwich enzyme immunoassay for TIMP-1 and by an assay for
      matrix metalloproteinase inhibition. The amount of TIMP-1 in the cytosolic
      fraction of quiescent Gin-1 cells after stimulation by fetal calf serum increased
      continuously for 48 hours, whereas that in the nuclear extract showed a maximum
      at 24 hours (S phase) and significantly decreased thereafter. Gin-1 cells
      expressed mRNAs for both TIMP-2 and TIMP-3 together with mRNA for TIMP-1.
      However, neither TIMP-2 nor TIMP-3 proteins seemed to accumulate in the nuclei of
      Gin-1 cells. These facts strongly suggest that TIMP-1 accumulates specifically in
      the nuclei of Gin-1 cells in a cell cycle-dependent manner.

PMID- 9547293
TI  - Osteopontin is a ligand for the alpha4beta1 integrin.
AB  - Recent work has shown that osteopontin expression is upregulated at sites of
      cardiovascular injury. It has been hypothesized that osteopontin provides an
      adhesive matrix for endothelial and smooth muscle cells during remodeling of the
      vascular wall following injury. Osteopontin has also been found to be synthesized
      by monocytes and macrophages within injury sites. Here, we present data showing
      that osteopontin can promote leukocyte adhesion through the alpha4beta1 integrin.
      In the presence of physiologic concentrations of Mg2+ and Ca2+, osteopontin
      purified from bovine milk promoted cell-substrate adhesion of HL-60 and Ramos
      cells, two model leukocyte cell lines. As with other adhesive ligands, adhesion
      to osteopontin required leukocyte activation. Under these conditions, no adhesion
      to control substrates such as bovine serum albumin was observed. Leukocyte
      adhesion was inhibited by anti-integrin antibodies directed at either the alpha4
      or beta1 integrin subunits but not by control antibodies directed to other
      integrins. Further adhesion experiments revealed that leukocyte binding to
      osteopontin was completely inhibited by an alpha4beta1-binding peptide containing
      the leucine-aspartate-valine (LDV) sequence, while a control, non-binding peptide
      containing leucine-glutamate-valine (LEV) had minimal effects. Affinity
      chromatography using either surface labeled HL-60 or Ramos cell extracts revealed
      that the alpha4beta1 integrin specifically bound to osteopontin.
      Immunoprecipitation of eluted fractions from these columns positively identified
      the alpha4beta1 integrin. In order to localize potential alpha4beta1-binding
      sites within osteopontin, the protein was proteolytically cleaved with thrombin.
      A 30 kDa N-terminal osteopontin fragment purified using fast protein liquid
      chromatography promoted alpha4beta1 dependent leukocyte adhesion in a manner
      similar to that of the intact protein. These data collectively demonstrate that
      the alpha4beta1 integrin is a new adhesion receptor for osteopontin and that an
      alpha4beta1 binding site exists in the NH2-terminal thrombin fragment of
      osteopontin.

PMID- 9547294
TI  - Vitronectin regulates smooth muscle contractility via alphav and beta1 integrin.
AB  - Previous work from this laboratory has established a method for maintaining
      physiological contractility of dissociated avian smooth muscle in a defined
      medium at low density. The present report emphasizes the dramatic potency of
      serum to alter smooth muscle phenotype and induce a loss of contractility.
      Vitronectin, a molecule purified from plasma, mimicked these effects of serum via
      an integrin that is RGD-sensitive. Studies utilizing blocking antibodies against
      vitronectin demonstrated that the presence of this specific adhesion molecule was
      necessary for the serum-induced loss of contractility. Based on the actions of
      function-blocking antibodies and RGD-containing peptides, the integrin
      alphavbeta1 appears to be the primary receptor involved in vitronectin's ability
      to induce phenotypic transformation in amniotic smooth muscle. The influence of
      vitronectin on smooth muscle contractility is particularly relevant, because this
      molecule is abundant in whole blood and plasma (approx. 400 microg/ml). The
      results suggest that smooth muscle needs to be continually protected from normal
      blood constituents in vivo. The implications of these results for smooth muscle
      related diseases like atherosclerosis, restenosis and Kaposi's sarcoma are
      discussed.

PMID- 9547295
TI  - Up-regulation of p27Kip1, p21WAF1/Cip1 and p16Ink4a is associated with, but not
      sufficient for, induction of squamous differentiation.
AB  - Irreversible growth arrest is an early and integral part of squamous cell
      differentiation in normal human epidermal keratinocytes (NHEKs) and is assumed to
      be linked to the control of expression of differentiation-specific genes. In this
      study, we examine the link between the molecular events associated with growth
      arrest and the expression of differentiation genes. NHEKs that have been induced
      to undergo growth arrest and differentiation by suspension culture contain
      populations in both G1 and G2/M of the cell cycle. The irreversible growth arrest
      state in NHEKs is characterized by an accumulation of the hypophosphorylated
      forms of Rb and p130, with subsequent down-regulation of levels of Rb, up
      regulation of p130 and associated down-regulation of E2F-regulated genes such as
      cyclin A. These events correlate with an inhibition of G1 cdk activity, mediated
      in part by an increase in the cdk inhibitors p21(WAF1/Cip1), p27(Kip1) and
      p16(Ink4a). Flow cytometric and immunoblot analysis demonstrated that the timing
      of the up-regulation of p27, p16 and p130 corresponds closely with the induction
      of the squamous-specific genes cornifin alpha (SPRR-1) and transglutaminase type
      I, suggesting a close link between control of growth arrest and differentiation.
      However, growth arrest induced by over-expression of p27, p21 or p16 by
      recombinant adenovirus is not sufficient to induce expression of the
      differentiation genes, or to invoke the pattern of cell cycle regulatory protein
      expression characteristic of the differentiation-specific irreversible growth
      arrest. We conclude that growth arrest mediated by activation of the Rb pathway
      is not sufficient to trigger terminal squamous differentiation and additional
      signals which can be generated during suspension culture are required to promote
      the complete differentiation program.

PMID- 9547296
TI  - Opposite sorting and transcytosis of the polymeric immunoglobulin receptor in
      transfected endothelial and epithelial cells.
AB  - We have transfected a polarised endothelial cell line, ECV 304, and an epithelial
      cell line, MDCK, with a well characterised epithelial protein, the rat polymeric
      immunoglobulin receptor (pIgR), in order to study the protein sorting and
      transcytosis in endothelial cells. The expressed protein was normally processed
      and the steady state distribution between apical and basolateral surfaces was
      similar in both cell types. MDCK cells, however, showed a marked polarity in the
      delivery of newly synthesised pIgR to the cell surface, and in the release of
      secretory component. 88% of newly synthesised pIgR in MDCK cells was first
      delivered to the basolateral surface and 99% of secretory component was released
      from the apical surface. In contrast the basolateral targeting signal of pIgR was
      only partially recognised in endothelial cells, with 63% of the newly synthesised
      pIgR being first delivered to the basolateral surface. At steady state only 43%
      of the pIgR was found on the basolateral membrane. The direction of dimeric IgA
      transcytosis in endothelial cells was from apical to basolateral surfaces,
      opposite to that in MDCK cells. These data suggest that endothelial cells poorly
      recognise the targeting signals of proteins from epithelial cells, and that the
      direction of transcytosis is linked to the biological role of the cells.

PMID- 9547297
TI  - Myofibrillar interaction of cytosolic creatine kinase (CK) isoenzymes: allocation
      of N-terminal binding epitope in MM-CK and BB-CK.
AB  - The molecular origin of the isoenzyme-specific interaction of cytosolic creatine
      kinase isoenzymes, muscle-type creatine kinase and brain-type creatine kinase,
      with myofibrillar structures has been studied by confocal microscopy in an
      functional in situ binding assay with chemically skinned, unfixed skeletal muscle
      fibers using wild-type and chimeric creatine kinase isoproteins. The specific
      interaction of both wild-type isoforms with the sarcomeric structure resulted in
      a stable, isoform-characteristic labeling pattern with muscle-type creatine
      kinase bound exclusively and tightly to the sarcomeric M-band while brain-type
      creatine kinase was confined to the I-band region. Chimeric proteins of both
      muscle-type and brain-type creatine kinases were constructed to localize the
      corresponding binding domain(s). Exchanged domains included the N-terminal part
      (residues 1-234), the region containing an isoenzyme 'diagnostic box' (residues
      235-285) and the C-terminal part (residues 286-380). The purified recombinant
      proteins were all fully intact and enzymatically active. All chimeric proteins
      containing the N-terminal region (amino acid 1-234) of muscle-type or brain-type
      creatine kinase were always specifically targeted to the sarcomeric M-band or I
      band, respectively. We therefore propose that the relevant epitope(s),
      determining the isoenzyme-specific targeting in skeletal muscle, are entirely
      located within the N-terminal regions of both cytosolic creatine kinase isoforms.

PMID- 9547298
TI  - Roles of Ca2+, inositol trisphosphate and cyclic ADP-ribose in mediating
      intercellular Ca2+ signaling in sheep lens cells.
AB  - To further characterize how gap junction-dependent Ca2+ waves propagate between
      sheep lens cells, we examined the possible roles of inositol 1,4,5-trisphosphate
      (IP3), Ca2+ and cyclic ADP-ribose (cADPR) in mediating intercellular Ca2+ waves.
      Second messengers were microinjected into a single cell in a monolayer of sheep
      lens cells while monitoring cytosolic Ca2+ with fura-2 and fluorescence
      microscopy. All three compounds initiated intercellular Ca2+ waves, but more
      cells responded following the injection of either IP3 or cADPR than responded
      following the injection of Ca2+. When either IP3 or cADPR was co-injected with
      the Ca2+ chelator EGTA, cytosolic Ca2+ in the injected cell decreased but
      cytosolic Ca2+ in the adjacent cells increased, indicating that the intercellular
      messenger was IP3 or cADPR, rather than Ca2+. The phospholipase C inhibitor
      U73122 eliminated mechanically initiated intercellular Ca2+ waves, indicating
      that mechanical initiation probably requires IP3 production. In U73122-treated
      cells, injected IP3 initiated an intercellular Ca2+ wave in which the number of
      cells responding increased as the amount of IP3 injected increased, indicating
      that the distance traveled by the Ca2+ wave was dependent on cell-to-cell
      diffusion of IP3. In contrast, the ability of cADPR both to increase cytosolic
      Ca2+ in the injected cell and to initiate intercellular Ca2+ waves was greatly
      attenuated by U73122. In conclusion, Ca2+, IP3 and cADPR can all mediate
      intercellular Ca2+ waves by passing through gap junction channels, but both IP3
      and cADPR are more effective intercellular messengers than Ca2+.

PMID- 9547299
TI  - Microtubule-mediated centrosome motility and the positioning of cleavage furrows
      in multinucleate myosin II-null cells.
AB  - To study centrosome motility and the interaction of microtubules with the cell
      cortex in mitotic, post-mitotic and interphase cells, (alpha)-tubulin was tagged
      in Dictyostelium discoideum with green fluorescent protein. Multinucleate cells
      formed by myosin II-null mutants proved to be especially suited for the analysis
      of the control of cleavage furrow formation by the microtubule system. After
      docking of the mitotic apparatus onto the cell cortex during anaphase, the cell
      surface is activated to form ruffles on top of the asters of microtubules that
      emanate from the centrosomes. Cleavage furrows are initiated at spaces between
      the asters independently of the positions of spindles. Once initiated, the
      furrows expand as deep folds without a continued connection to the microtubule
      system. Occurrence of unilateral furrows indicates that a closed contractile ring
      is dispensable for cytokinesis in Dictyostelium. The progression of cytokinesis
      in the multinucleate cells underlines the importance of proteins other than
      myosin II in specifying a cleavage furrow. The analysis of centrosome motility
      suggests a major role for a minus-end directed motor protein, probably
      cytoplasmic dynein, in applying traction forces on guiding microtubules that
      connect the centrosome with the cell cortex.

PMID- 9547300
TI  - Identification of an interchromosomal compartment by polymerization of nuclear
      targeted vimentin.
AB  - A number of structural and functional subnuclear compartments have been
      described, including regions exclusive of chromosomes previously hypothesized to
      form a reactive nuclear space. We have now explored this accessible nuclear space
      and interchromosomal nucleoplasmic domains experimentally using Xenopus vimentin
      engineered to contain a nuclear localization signal (NLS-vimentin). In stably
      transfected human cells incubated at 37 degrees C, the NLS-vimentin formed a
      restricted number of intranuclear speckles. At 28 degrees C, the optimal
      temperature for assembly of the amphibian protein, NLS-vimentin progressively
      extended with time out from the speckles into strictly orientated intranuclear
      filamentous arrays. This enabled us to observe the development of a system of
      interconnecting channel-like areas. Quantitative analysis based on 3-D imaging
      microscopy revealed that these arrays were localized almost exclusively outside
      of chromosome territories. During mitosis the filaments disassembled and
      dispersed throughout the cytoplasm, while in anaphase-telophase the vimentin was
      recruited back into the nucleus and reassembled into filaments at the chromosome
      surfaces, in distributions virtually identical to those observed in the previous
      interphase. The filaments also colocalized with specific nuclear RNAs, coiled
      bodies and PML bodies, all situated outside of chromosome territories, thereby
      interlinking these structures. This strongly implies that these nuclear entities
      coexist in the same interconnected nuclear compartment. The assembling NLS
      vimentin is restricted to and can be used to delineate, at least in part, the
      formerly proposed reticular interchromosomal domain compartment (ICD). The
      properties of NLS-vimentin make it an excellent tool for performing structural
      and functional studies on this compartment.

PMID- 9547302
TI  - Two visual pigments in a single photoreceptor cell: identification and
      histological localization of three mRNAs encoding visual pigment opsins in the
      retina of the butterfly Papilio xuthus.
AB  - This paper describes the localization of newly identified visual pigment opsins
      in the tiered retina of the Japanese yellow swallowtail Papilio xuthus. We first
      cloned three cDNAs encoding visual pigment opsins, PxRh1, PxRh2 and PxRh3, and
      then carried out histological in situ hybridization to localize their mRNAs in
      the retina. By combining the present data with our previous electrophysiological
      results, we concluded that both PxRh1 and PxRh2 correspond to visual pigments
      expressed in photoreceptor cells sensitive in the green wavelength region (green
      receptors), whereas PxRh3 corresponds to a pigment in red receptors. The in situ
      hybridization studies showed that some photoreceptor cells express two opsin
      mRNAs. In the ventral half of the eye, all green receptors in the distal tier
      were labelled by both PxRh1 and PxRh2 probes. The labelling by the PxRh2 and
      PxRh3 probes was detected throughout the eye in the proximal tier; in 18 % of
      ommatidia, the probes labelled the same photoreceptor cell. These results suggest
      that the possible co-localization of two different visual pigments will broaden
      the sensitivity spectrum of the photoreceptor cells.

PMID- 9547301
TI  - Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and
      RBM during human germ cell development.
AB  - RBM is a germ-cell-specific RNA-binding protein encoded by the Y chromosome in
      all mammals, implying an important and evolutionarily conserved (but as yet
      unidentified) function during male germ cell development. In order to address
      this function, we have developed new antibody reagents to immunolocalise RBM in
      the different cell types in the human testis. We find that RBM has a different
      expression profile from its closest homologue hnRNPG. Despite its ubiquitous
      expression in all transcriptionally active germ cell types, RBM has a complex and
      dynamic cell biology in human germ cells. The ratio of RBM distributed between
      punctate nuclear structures and the remainder of the nucleoplasm is dynamically
      modulated over the course of germ cell development. Moreover, pre-mRNA splicing
      components are targeted to the same punctate nuclear regions as RBM during the
      early stages of germ cell development but late in meiosis this spatial
      association breaks down. After meiosis, pre-mRNA splicing components are
      differentially targeted to a specific region of the nucleus. While pre-mRNA
      splicing components undergo profound spatial reorganisations during
      spermatogenesis, neither heterogeneous ribonucleoproteins nor the transcription
      factor Sp1 show either developmental spatial reorganisations or any specific co
      localisation with RBM. These results suggest dynamic and possibly multiple
      functions for RBM in germ cell development.

PMID- 9547303
TI  - Rhodopsin-like proteins in planarian eye and auricle: detection and functional
      analysis
AB  - The presence of rhodopsin-like proteins in the eyes and auricles of the
      freshwater planarian Dugesia japonica was confirmed using anti-frog-rhodopsin
      rabbit IgG. The apparent relative molecular masses of these proteins were
      65x10(3) and 62x10(3), and positive reactions to IgG were localized to the
      microvilli of the photoreceptor cells in the eyes and to the sensory cilia,
      rootlets and microvilli in the auricles. Eye- or head-excised planarians showed
      no negative phototaxis, whereas intact or auricle-excised planarians did. During
      regeneration in head-excised planarians, the appearance of rhodopsin-like
      proteins in the regenerating eyes corresponded to the recovery of negative
      phototaxis behaviour. Head or auricle excision enhanced asexual fission under
      continuous illumination. However, eye excision had no such effect. These results
      suggest that the rhodopsin-like proteins in the eyes work as photoreceptors for
      negative phototaxis behaviour and that, in the auricles, they are involved in
      asexual fission originating from the circadian rhythm.

PMID- 9547305
TI  - Intracellular electrolyte levels and transport of secretory granules in exocrine
      gland cells 
AB  - We demonstrate the intracellular transport of secretory granules of a silk
      protein, fibroin, from the Golgi region to the apical cytoplasm with special
      reference to microtubule organization, electrolyte concentrations and the acidic
      intragranular pH of normal and mutant posterior silk gland cells, using the
      techniques of electrophysiological microelectrode and microprobe analysis and of
      light and electron microscopic autoradiography. The silk gland cells of a
      recessive mutant making only flimsy cocoons were defective in the microtubule
      systems, did not stain with an anti-tubulin antibody in immunofluorescent
      microscopy, and accumulated intracellular granules in the apical and basal
      cytoplasm. The increase in intracellular calcium concentration and levels of
      chloride secretion were also reduced in the mutant cells. A carboxylic ionophore,
      monensin, which collapsed the granular H+ gradient, induced the transport of
      chloride and an increase in the intracellular calcium concentration, while it
      blocked the intracellular transport of granules from the Golgi region to the
      apical cytoplasm in normal cells. Thus, we conclude that the H+ gradient across
      the membrane of secretory granules is responsible for the intracellular transport
      of the secretory granules along the microtubule systems in silk gland cells,
      while Ca2+ is thought to be required for the exocytosis of the granules.

PMID- 9547304
TI  - Microtubules facilitate the stimulated secretion of beta-hexosaminidase in
      lacrimal acinar cells.
AB  - Stimulation of lacrimal acini with secretagogues such as carbachol initiates
      movement and fusion of acinar secretory vesicles with the apical plasma membrane,
      resulting in release of protein into the nascent tear fluid. Using rabbit
      lacrimal acini reconstituted in vitro from isolated cells, we have investigated
      the organization of the apical cytoskeleton and its role in stimulated secretion.
      Confocal microscopy revealed a microtubule array emanating from the apical region
      of the acini; the apical region was also enriched in microfilaments and (gamma)
      tubulin. Cytokeratin-based intermediate filaments were apically concentrated, and
      also detected at the cell periphery. Neither confocal microscopy nor biochemical
      analysis revealed any reorganization of lumenal microfilaments or microtubules
      which might accompany carbachol-stimulated release of secretory proteins.
      However, major changes in the acinar microtubule array induced by taxol or
      nocodazole were correlated with inhibition of carbachol-dependent release of the
      secreted protein, beta-hexosaminidase. Major changes in lumenal microfilaments
      induced by jasplakinolide or cytochalasin D did not inhibit the carbachol
      dependent release of beta-hexosaminidase; rather, release of beta-hexosaminidase
      from jasplakinolide- or cytochalasin D-treated carbachol-stimulated acini was
      markedly increased relative to the release from untreated stimulated acini. Our
      findings demonstrate that microtubules play a major role in stimulated lacrimal
      secretion, and suggest a contributory role for microfilaments.

PMID- 9547307
TI  - Neuronal mechanisms underlying the facilitatory control of uropod steering
      behaviour during treadmill walking in crayfish. I. Antagonistically regulated
      background excitability of uropod motoneurones 
AB  - One of the postural reflexes of crayfish, the uropod steering response, is
      elicited by specific sensory inputs while the animal is walking. It is not
      elicited, however, by the same inputs when the animal is at rest. To clarify the
      neuronal mechanisms underlying this facilitatory control of body posture in the
      active animals, we used intracellular recordings to analyse the synaptic
      activities of uropod motor system neurones in an unanaesthetized whole-animal
      preparation. Several uropod motoneurones were found to receive sustained
      depolarizing inputs during walking, whereas the walking leg motoneurones sampled
      always showed rhythmic activity. The membrane conductance of the uropod
      motoneurones increased during the sustained synaptic activity. Premotor
      nonspiking interneurones showed depolarizing or hyperpolarizing membrane
      potential changes during walking that were also accompanied by increases in
      membrane conductance. Some of these interneurones enhanced uropod motoneurone
      activity, whereas others suppressed it during walking. These results suggest that
      the background excitability of uropod motoneurones is kept at an intermediate
      level during walking by the antagonistic inputs from premotor nonspiking
      interneurones so that the uropod motor system can be responsive to both further
      excitatory and inhibitory inputs resulting from postural changes. <P>

PMID- 9547306
TI  - The distribution and translocation of the G protein ADP-ribosylation factor 1 in
      live cells is determined by its GTPase activity.
AB  - ADP-ribosylation factors (ARF) are small G proteins that play key roles in
      vesicular transport processes. We have studied the distribution of ARF1 in live
      cells using chimeras of ARF1 mutants (wild type (wt) ARF1; Q71L-ARF1 (reduced
      GTPase); T31N (low affinity for GTP); and (Delta)Nwt (deletion of amino acids 2
      18)) with green fluorescent protein (GFP). Confocal microscopy studies showed
      that the wt and Q71L proteins were localized in the Golgi and cytoplasm. The
      (Delta)Nwt and the T31N mutants were exclusively cytoplasmic. The behavior of the
      wt and Q71L proteins was studied in detail. About 15% of wt-ARF1-GFP was bound to
      the Golgi. Bound wt-ARF1-GFP dissociated rapidly after addition of Brefeldin A
      (BFA). This process did not appear to be a consequence of BFA-induced
      disappearance of the Golgi. Photobleaching recovery showed that essentially all
      the ARF-GFP was mobile, although it diffused very slowly. In contrast, about 40
      50% of the Q71L mutant was found in the Golgi, and its rate of dissociation in
      the presence of BFA was slow and biphasic. Q71L-ARF1-GFP diffused more slowly
      than the wt. We conclude that ARF1 proteins exist in a dynamic equilibrium
      between Golgi-bound and cytosolic pools, and that the translocation of ARF in
      live cells requires the hydrolysis of GTP by the Golgi-bound protein.

PMID- 9547308
TI  - Actin mRNA isoforms are differentially sorted in normal osteoblasts and sorting
      is altered in osteoblasts from a skeletal mutation in the rat.
AB  - Actin isoform sorting has been shown to occur in a variety of cell types in
      culture. To this list we add osteoblasts, in which we show by in situ
      hybridization that beta-actin is distributed primarily in cell processes and on
      one side of the nucleus and gamma-actin has a perinuclear distribution.
      Osteoblasts from the skeletal mutation toothless (tl), evaluated under identical
      conditions, fail to sort these actin isoforms differentially and exhibit diffuse
      labeling as their major manifestation. Northern analyses of actin mRNAs showed no
      differences between normal and mutant cultures. Shortened osteoblast life span
      and an inability to direct osteoclast-mediated bone resorption have recently been
      demonstrated in tl mutants. The present results suggest that a failure of
      osteoblasts to sort actin mRNAs may be related to one or both of these
      pathological manifestations in this mutation and represent, to our knowledge, the
      first correlation of an actin mRNA-sorting abnormality with a mammalian disease.

PMID- 9547309
TI  - Nuclear envelope disassembly in mitotic extract requires functional nuclear pores
      and a nuclear lamina.
AB  - Using sea urchin embryonic and in-vitro-assembled nuclei incubated in sea urchin
      mitotic extract, I provide evidence for a requirement for functional nuclear
      pores and a nuclear lamina for nuclear envelope disassembly in vitro. In
      interphase gastrula nuclei, lamin B interacts with p56, an integral protein of
      inner nuclear membrane cross-reacting with antibodies to human lamin B receptor.
      Incubation of gastrula nuclei in mitotic cytosol containing an ATP-generating
      system rapidly induces hyperphosphorylation of p56 and lamin B. Subsequently, p56
      lamin B interactions are weakened and the two proteins segregate into distinct
      nuclear envelope-derived vesicles upon disassembly of nuclear membranes and of
      the lamina. Nuclear disassembly is accompanied by chromatin condensation.
      Blocking nuclear pore function with wheat germ agglutinin or antibodies to
      nucleoporins prevents p56 and lamin B hyperphosphorylation, nuclear membrane
      breakdown and lamina solubilization. These events are not rescued by
      permeabilization of nuclear membranes to molecules of 150, 000 Mr with
      lysolecithin. In-vitro-assembled nuclei containing nuclear membranes with
      functional pores but no lamina do not disassemble in mitotic cytosol in spite of
      p56 hyperphosphorylation. Nuclear import of soluble lamin B and reformation of a
      lamina in interphase extract restores nuclear disassembly in mitotic cytosol. The
      data indicate a role for functional nuclear pores in nuclear disassembly in
      vitro. They show that p56 hyperphosphorylation is not sufficient for nuclear
      membrane disassembly in mitotic cytosol and argue that the nuclear lamina plays a
      critical role in nuclear disassembly at mitosis.

PMID- 9547310
TI  - Neuronal mechanisms underlying the facilitatory control of uropod steering
      behaviour during treadmill walking in crayfish. II. Modulation Of uropod
      motoneurone excitation by leg proprioception 
AB  - The synaptic activities underlying the uropod steering behaviour of crayfish
      evoked by tilting the substratum beneath the legs have been studied
      intracellularly in unanaesthetized animals standing or walking on a treadmill.
      The uropod motoneurones showed little or no synaptic response when the treadmill
      was tilted while the animal was in a quiescent state and the membrane potential
      was at its resting value. When the same stimulus was given while the animal was
      walking or in an active stance on the treadmill, the motoneurones showed
      transient much-enhanced excitatory or inhibitory responses to tilt, depending on
      the tilt direction. These responses were superimposed on a sustained level of
      background excitation so that the spike activity of the motoneurones either
      increased or decreased. Premotor nonspiking interneurones also showed little or
      no synaptic response to the tilt stimulus while the animal was resting, but
      greatly enhanced responses, in either a depolarizing or a hyperpolarizing
      direction, while the animal was walking or in the active-standing state. The
      results indicate that the proprioceptor inputs converging onto the uropod
      motoneurones, either directly or through premotor nonspiking interneurones, are
      gated not only in the uropod motor system in the terminal abdominal ganglion but
      also at as yet unidentified sites upstream in anterior ganglia, thus suggesting
      multiple gate control of the descending proprioceptor pathway.

PMID- 9547312
TI  - Multilayer reflectors in animals using green and gold beetles as contrasting
      examples 
AB  - The light reflectors in the beetles Calloodes grayanus and Anoplognathus parvulus
      are examined. Contrasting multilayer reflectors are revealed. Calloodes grayanus
      appears a weak green colour, matching its background leaves, while A. parvulus is
      strongly metallic-gold coloured. The former reflection is diffuse, as the result
      of a structure causing scattering that overlies the multilayer reflector, whereas
      the latter reflection is strongly directional. The green colour of C. grayanus is
      achieved by a multilayer reflector with a fixed spatial periodicity, here termed
      'regular', which is far removed from the quarterwave, or physically 'ideal',
      condition. The gold colour of A. parvulus is achieved by a type of reflector
      which involves systematically changing optical thicknesses of the component
      layers with depth in the structure. A layer of melanin underlies the reflector of
      C. grayanus to absorb the transmitted portion of light and prevent its back
      reflectance, which would otherwise alter the green colour. The resultant
      structural reflectance from C. grayanus effectively matches green pigments, which
      are rare in beetles.

PMID- 9547311
TI  - Contributions of extracellular and intracellular domains of full length and
      chimeric cadherin molecules to junction assembly in epithelial cells.
AB  - The integrity of cell-cell junctions in epithelial cells depends on functional
      interactions of both extracellular and intracellular domains of cadherins with
      other junction proteins. To examine the roles of the different domains of E
      cadherin and desmoglein in epithelial junctions, we stably expressed full length
      desmoglein 1 and chimeras of E-cadherin and desmoglein 1 in A431 epithelial
      cells. Full length desmoglein 1 was able to incorporate into or disrupt
      endogenous desmosomes depending on expression level. Each of the chimeric
      cadherin molecules exhibited distinct localization patterns at the cell surface.
      A chimera of the desmoglein 1 extracellular domain and the E-cadherin
      intracellular domain was distributed diffusely at the cell surface while the
      reverse chimera, comprising the E-cadherin extracellular domain and the
      desmoglein 1 intracellular domain, localized in large, sometimes contiguous
      patches at cell-cell interfaces. Nevertheless, both constructs disrupted
      desmosome assembly. Expression of constructs containing the desmoglein 1
      cytoplasmic domain resulted in approximately a 3-fold decrease in E-cadherin
      bound to plakoglobin and a 5- to 10-fold reduction in the steady-state levels of
      the endogenous desmosomal cadherins, desmoglein 2 and desmocollin 2, possibly
      contributing to the dominant negative effect of the desmoglein 1 tail. In
      addition, biochemical analysis of protein complexes in the stable lines revealed
      novel in vivo protein interactions. Complexes containing beta-catenin and
      desmoglein 1 were identified in cells expressing constructs containing the
      desmoglein 1 tail. Furthermore, interactions were identified between endogenous E
      cadherin and the chimera containing the E-cadherin extracellular domain and the
      desmoglein 1 intracellular domain providing in vivo evidence for previously
      predicted lateral interactions of E-cadherin extracellular domains.

PMID- 9547313
TI  - Curve walking in freely moving crayfish (Procambarus clarkii) 
AB  - The curve walking of freely moving crayfish trained to walk along a curved path
      during homing behaviour was investigated using a video-analysis system. The leg
      kinematics and leg phase relationships, as well as the relationship between
      stepping patterns and body axis rotation measured relative to external
      references, were studied. <P> The anterior and posterior extreme positions of the
      power stroke (AEP and PEP, respectively) and step amplitudes were analysed. As in
      a previous study on crayfish curve walking on a treadmill, PEPs were more
      posterior in outer legs (the legs on the outside of the turn) than in the inner
      legs. As a result, outer legs showed larger step amplitudes than inner legs. Leg
      kinematics varied within each walking sequence. AEP leg angles (the angles
      between the body and leg axes at the AEP) tended to decrease over time for inner
      legs and increase for outer legs. This leg angle drift was present mainly in the
      anterior legs and it suggests that these legs did not completely compensate for
      the body rotation after each step. In addition, leg angle asymmetries in a
      direction opposite to that of leg angle drift were observed at the start of each
      curve-walking sequence, suggesting that the extensive training (3 weeks) may have
      allowed crayfish to anticipate the leg angle drift. <P> The rotational component
      of curve walking showed a discontinuous pattern, with the animal's body axis
      turning towards the inside of the curve only periodically. Analysis of cross
      correlation functions showed that the angular acceleration of the body axis in
      the direction of the turn occurred during the power strokes of inner legs 2 and 5
      and outer leg 4. While the tripod formed by these three legs showed in-phase
      relationships, the legs of the corresponding contralateral tripod (outer legs 2
      and 5 and inner leg 4) were not in phase. We hypothesize that inner legs 2 and 5
      and outer leg 4 act synergically causing the inward body rotation observed in
      curve-walking crayfish and that some of the asymmetries found in step geometry
      may be a passive phenomenon due to the body rotation.

PMID- 9547314
TI  - Orthodromically and antidromically evoked local field potentials in the crayfish
      olfactory lobe 
AB  - A local field potential, consistent in form and duration, can be recorded from
      the olfactory lobe of crayfish following electrical stimulation of the outer
      flagellum of the antennule. The field potential is reversibly blocked by
      perfusion of the brain with low-[Ca2+] saline or <IMG
      src="/images/symbols/gamma.gif" WIDTH="9" HEIGHT="12" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">-aminobutyric acid and, to a lesser extent, histamine. Paired
      shocks to the antennule and antidromic electrical stimulation of olfactory lobe
      output neurones also partially block the field potential. Comparing the field
      potential with simultaneously recorded intracellular responses of olfactory
      interneurones reveals a coincidence between excitatory and inhibitory effects in
      the interneurones and the appearance of identifiable components of the field
      potential. We interpret the field potential to reflect the response of neural
      elements in the olfactory lobe to orthodromic activity in the axons of the
      olfactory receptor neurones on the antennule. We conclude from the blocking
      experiments that the greater part of the field potential stems from neurones in
      the olfactory lobe that are postsynaptic to olfactory receptor neurones. As such,
      it provides a robust indication of olfactory neurone activity.

PMID- 9547315
TI  - Conservation and variation in the feeding mechanism of the spiny dogfish squalus
      acanthias 
AB  - Changes in the feeding mechanism with feeding behavior were investigated using
      high-speed video and electromyography to examine the kinematics and motor pattern
      of prey capture, manipulation and transport in the spiny dogfish Squalus
      acanthias (Squalidae: Squaliformes). In this study, Squalus acanthias used both
      suction and ram behaviors to capture and manipulate prey, while only suction was
      used to transport prey. The basic kinematic feeding sequence observed in other
      aquatic-feeding lower vertebrates is conserved in the spiny dogfish. Prey
      capture, bite manipulation and suction transport events are characterized by a
      common pattern of head movements and motor activity, but are distinguishable by
      differences in duration and relative timing. In general, capture events are
      longer in duration than manipulation and transport events, as found in other
      aquatic-feeding lower vertebrates. Numerous individual effects were found,
      indicating that individual sharks are capable of varying head movements and motor
      activity among successful feeding events. Upper jaw protrusion in the spiny
      dogfish is not restricted by its orbitostylic jaw suspension; rather, the upper
      jaw is protruded by 30 % of its head length, considerably more than in the lemon
      shark Negaprion brevirostris (Carcharhinidae: Carcharhiniformes) (18 %) with its
      hyostylic jaw suspension. One function of upper jaw protrusion is to assist in
      jaw closure by protruding the upper jaw as well as elevating the lower jaw to
      close the gape, thus decreasing the time to jaw closure. The mechanism of upper
      jaw protrusion was found to differ between squaliform and carcharhiniform sharks.
      Whereas the levator palatoquadrati muscle assists in retracting the upper jaw in
      the spiny dogfish, it assists in protruding the upper jaw in the lemon shark.
      This study represents the first comprehensive electromyographic and kinematic
      analysis of the feeding mechanism in a squaliform shark.

PMID- 9547316
TI  - Ventilation and acid-base recovery following exhausting activity in an air
      breathing fish 
AB  - The effects of exhausting activity in normoxic (PO2=20.7 kPa) and hypoxic
      (PO2<2.7 kPa) water on ventilatory, metabolic and acid-base variables were
      examined in spotted gar (Lepisosteus oculatus) to determine the role of the air
      breathing organ in supporting active metabolism and recovery. The level of
      aquatic hypoxia used effectively eliminated the gills as a site of O2 uptake,
      forcing the fish to respire as a unimodal air-breather. Swimming duration (until
      exhaustion) was not significantly different in normoxic and hypoxic water. Blood
      gas, acid-base, cardiovascular and ventilatory variables were monitored at
      intervals from 15 min to 24 h post-exercise. Fish survived exhaustive exercise
      using a combination of anaerobic metabolism and increased ventilation (aerial and
      aquatic), despite respiratory and metabolic acidoses. The cardiovascular effects
      of exercise (heart rate and dorsal aortic blood pressure) were minor. The
      metabolic effects of exercise were similar to those in unimodal water-breathing
      fish; however, even hypoxic animals recovered from exhaustive exercise by 24 h.
      Thus, the results of this study show that air breathing in L. oculatus allows gar
      to exercise to the same extent in normoxic and hypoxic water and enables them to
      re-establish blood gas and acid-base balance after exhaustive activity even in
      hypoxic water. <P>

PMID- 9547317
TI  - A note on interactions between temperature, viscosity, body size and swimming
      energetics in fish larvae 
AB  - In a previous study, it was shown that at a given speed the larvae of a species
      of freshwater fish, the Danube bleak Chalcalburnus chalcoides, expended
      considerably more metabolic energy at 15 degreesC than at 20 degreesC. We applied
      hydromechanical arguments to our previous data in order to determine whether the
      higher cost of swimming at the lower temperature might be due to the effects of
      viscous forces. However, even under the unrealistic assumption of the larvae
      swimming in the viscous regime at Reynolds numbers as high as 2000, we show here
      that hydromechanical forces cannot explain the high energy cost of swimming at 15
      degreesC. Instead, we offer a new hypothesis that the 'two-gear system' of the
      swimming muscles operating in juvenile and adult fish is not yet functional in
      the larvae, with the consequence that, when these fish are swimming at high
      speeds in cold water, the muscle fibres have to operate over an increasingly
      inefficient range of shortening velocities.

PMID- 9547318
TI  - The impact of endurance training on arterial plasma K+ levels and swimming
      performance of rainbow trout 
AB  - Arterial plasma K+ and lactate concentrations ([K+]a and [lactate]a), as well as
      blood oxygenation status, were measured in relation to increasing swimming speeds
      in rainbow trout Oncorhynchus mykiss. Neither [K+]a nor [lactate]a changed at
      swimming speeds below 1.5 BL s-1, where BL is total body length. Between 1.5 and
      2.0 BL s-1, [K+]a started to increase, and above 2.0 BL s-1 both [K+]a and
      [lactate]a increased with swimming speed. Training shifted the onset of these
      increases to higher swimming speeds and increased the critical swimming speed
      (Ucrit) from 2.4 to 3.0 BL s-1. Blood oxygen content showed no changes in control
      fish, whereas in trained fish it increased by 22 % at the final swimming speed.
      From the [K+]a data, we suggest that no loss of K+ occurred from the working
      muscle at low swimming speeds, allowing an unlimited endurance, whereas moderate
      and higher speeds were probably associated with a loss of K+ from the working
      muscles, indicating a limited endurance. <P>

PMID- 9547319
TI  - Tissue and whole-body extracellular, red blood cell and albumin spaces in the
      rainbow trout as a function of time: a reappraisal of the volume of the secondary
      circulation 
AB  - [58Co]EDTA, [51Cr]RBC and [125I]albumin spaces in the whole body and 28 tissue
      samples were examined at timed intervals over 16 h in rainbow trout Oncorhynchus
      mykiss. [58Co]EDTA space (which approximates extracellular fluid volume; ECF) in
      fins, skin, gallbladder and eye are reported for the first time. After a 16 h
      equilibration, ECF volume was large (376-726 microl g-1 wet tissue mass) in
      kidney, swimbladder, skin and fins, moderate (219-313 microl g-1 wet tissue mass)
      in stomach, skull, spleen, liver, intestine, gills, eye and cecum, and small (53
      181 microl g-1 wet tissue mass) in red muscle, fat, brain, gallbladder and white
      muscle. Whole-body ECF was 387+/-10.6 microl g-1 (mean +/- s.e.m.; N=11).
      [51Cr]RBC space relative to [58Co]EDTA space was large in spleen, liver,
      intestine and gill, and low in skin, fins, stomach and skull. Whole-body
      [51Cr]RBC space was 9.9+/-0.6 microl g-1 body mass (N=17). Blood volume
      calculated from [51Cr]RBC space at 16 h and a dorsal aortic hematocrit of 24.5 %
      was 40.4 microl g-1 body mass. Whole-body [125I]albumin space at 16 h was 118.0+/
      7.4 microl g-1 body mass (N=6), which resulted in an estimated blood volume of
      156. 6 microl g-1 body mass, nearly four times that estimated from the [51Cr]RBC
      space. Tissue hematocrits, calculated from [125I]albumin and [51Cr]RBC spaces,
      were significantly lower than dorsal aortic hematocrit in all tissues except
      spleen, kidney and liver. [58Co]EDTA and [51Cr]RBC spaces reached equilibrium in
      nearly all tissues within 1 h, whereas [125I]albumin continued to accumulate in
      many tissues up 24 h. The disparity between [125I]albumin distribution kinetics
      compared with the kinetics of [58Co]EDTA and [51Cr]RBC distribution, as well as
      the accumulation of [125I]albumin in tissues not known to have a secondary
      circulation, indicates that [125I]albumin is a poor marker of plasma volume in
      trout and that previous studies based on [125I]albumin clearance from the plasma
      have overestimated both the volume and the turnover rate of the secondary system.
      Revised estimates of secondary circulation volume, based on [58Co]EDTA
      distribution rate, indicate that it is no more than 10-20 % of the volume of the
      primary circulation. <P>

PMID- 9547320
TI  - Neuromuscular sensitivity to hydrogen sulfide in the marine invertebrate Urechis
      caupo.
AB  - Hydrogen sulfide (HS) is a well-known inhibitor of aerobic respiration via its
      reversible binding of mitochondrial cytochrome c oxidase, but recent studies have
      suggested that HS may have other non-respiratory actions. We have studied the
      effects of HS on spontaneous and evoked contractions in vitro under hypoxic and
      anoxic conditions in nerve-muscle preparations from the echiuran worm Urechis
      caupo. Contraction amplitude in response to electric field stimulation under
      anoxic conditions was completely abolished by HS within minutes in a classic dose
      response relationship (Kd=31 mmol l-1, r2=0.86). Exposure of body wall and
      esophagus to HS in vitro for up to 6 h demonstrated that the contraction
      amplitude and frequency of spontaneous activity were relatively insensitive to
      anoxia, but that the sensitivity to HS was similar to that seen in field
      stimulated muscle (Kd=2.7-32 mmol l-1). The toxic effects of HS were reversible,
      with almost complete recovery under anoxic conditions within the first hour.
      These data indicate that HS at millimolar concentrations can directly inhibit
      muscle contraction. Although the mechanism of this action is unknown, it does not
      appear to involve metabolic pathways or oxygen transport.

PMID- 9547322
TI  - Effect of cyclical salinity changes on cell volume and function in geukensia
      demissa gills 
AB  - We acclimated the estuarine mussel Geukensia demissa to a regime of sinusoidal
      salinity cycling (12 h cycle between 100 % and 60 % seawater) and correlated
      changes in the volume of gill cells with changes in several indicators of the
      functional status of gill cells (rate of O2 consumption, ATP content and amino
      acid transport). There was no indication of short-term volume regulation in the
      gill cells of mussels acclimated to salinity cycling. When exposed to cycling
      salinity, cell water space consistently increased to approximately 3 ml g-1 dry
      mass during the cycle troughs (60 % seawater) and returned to approximately 2 ml
      g-1 dry mass at the cycle peaks (100 % seawater). In mussels acclimated for 2
      weeks to cycling salinity, the gill contents of betaine, taurine and K+ were
      unchanged (approximately 240, 230 and 160 micromol g-1 dry mass, respectively)
      between the 60 % and 100 % seawater portions of the salinity cycle. The changes
      in cell volume did not appear to be associated with large perturbations in the
      functional status of cells. The rate of O2 consumption was approximately 100
      microl O2 g-1 dry mass min-1, and ATP content was approximately 30 micromol g-1
      protein, in all salinities to which mussels were exposed. Rates of uptake of
      taurine, leucine and phenylalanine decreased by approximately 50 % during the
      first sinusoidal decrease to 60 % seawater, but recovered following re-exposure
      to 100 % seawater. Uptake rates of all three amino acids were unaffected by any
      subsequent salinity cycles. These results suggest (1) that the regulation of gill
      cell volume is normally absent from mussels exposed to repeated, gradual salinity
      changes, and (2) that any effects of changes in cell volume are not severe enough
      to justify the energetic expenditure that would be associated with repeated
      regulation of cell volume. Unlike the response of gill cells to cycling salinity,
      there was a decrease in the solute contents of ventricles during the salinity
      troughs compared with the salinity peaks, suggesting that the presence of short
      term volume regulation may be more critical in the ventricle.

PMID- 9547321
TI  - Cell volume regulation in proximal renal tubules from trout (Salmo trutta).
AB  - Regulatory volume decrease (RVD) following hypo-osmotic stimulation was studied
      using videometric methods in isolated proximal renal tubules from trout (Salmo
      trutta). The relative tubule diameter increased by 132.0+/-4.8 % (maximum
      swelling within 1 min at 15 and 25 degrees C and within 4 min at 10 degrees C)
      following a change from iso-osmotic (290 mosmol kg-1) to hypo-osmotic (160 mosmol
      kg-1) Ringer's solution. The tubule diameter subsequently decreased to
      approximately one-quarter of the maximal value. Ouabain (1 mmol l-1) reduced cell
      swelling and inhibited the RVD response by 28.0+/-10.5 %. Furthermore, increasing
      the bath K+ concentration by 30 mmol l-1 inhibited RVD by 76.5+/-3.6 %. The K+
      channel blocker quinine, but not Ba2+ (1 and 2 mmol l-1), significantly decreased
      the RVD response (by 25.0+/-5.4 and 72.3+/-5.1 % at 0.1 and 0.5 mmol l-1,
      respectively). Similarly, increasing the Cl- concentration in the bath from 47 to
      102 mmol l-1 induced a significant reduction (45. 2+/-7.9 %) in RVD. The RVD
      response was also markedly reduced (by 54. 7+/-5.3 %) by the Cl- channel blocker
      indacrinone (MK-196; 0.5 mmol l-1), but only marginally by 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB; 1, 5, 8 and 10 micromol l-1). Addition of
      the K+/Cl- symport inhibitor furosemide (0.1 mmol l-1) resulted in a 39.8+/-3.9 %
      inhibition of RVD. This inhibition could be completely overcome by simultaneous
      administration of 1 micromol l-1 tributyltin (anion exchanger) and furosemide.
      Chelation of either extracellular (1 mmol l-1 EGTA) or both extra- and
      intracellular Ca2+ (1 mmol l-1 EGTA, 10 micromol l-1 A23187) had no effect on
      this RVD process. Furthermore, as measured using the fluorescent dye Fura-2/AM,
      there was no increase in the intracellular free Ca2+ concentration upon hypo
      osmotic stimulation. Administration of the 5-lipoxygenase antagonist ETH 615-139
      (20 micromol l-1), however, induced a 60 % inhibition of RVD. Simultaneous
      addition of ETH-615 and either the K+ ionophore gramicidin (0.5 mmol l-1) or the
      anion exchanger tributyltin (1 micromol l-1) could not reverse the ETH 615-139
      inhibition. Finally, administration of the cycloxygenase inhibitor indomethacin
      had only a small, but significant, effect on RVD. We conclude that RVD following
      hypo-osmotic swelling is in these cells a temperature- and ouabain-sensitive
      process that appears to be the result of K+ efflux through quinine-sensitive,
      Ba2+-insensitive K+ channels and Cl- efflux through an MK-196- and furosemide
      sensitive Cl- conductance that is relatively unaffected by NPPB. This KCl efflux
      seems to be regulated by eicosanoids produced by the 5-lipoxygenase. Arachidonic
      acid metabolites from the cycloxygenase pathway are not involved in this process.
      Similarly, neither extra- nor intracellular Ca2+ appears to be important for the
      signalling of RVD.

PMID- 9547323
TI  - Visual pigments, oil droplets and cone photoreceptor distribution in the european
      starling (Sturnus vulgaris) 
AB  - Microspectrophotometric measurements of retinal photoreceptors from the European
      starling (Sturnus vulgaris) revealed four classes of single cone, containing
      visual pigments with wavelengths of maximum absorbance (<IMG
      src="/images/symbols/lambda.gif" WIDTH="8" HEIGHT="12" ALIGN="BOTTOM"
      NATURALSIZEFLAG= "3">max) at 563, 504, 449 and close to 362 nm. The two longer
      wave-sensitive single cones contained brightly coloured oil droplets which cut
      off light below 572 and 514 nm, respectively. The 449 nm <IMG
      src="/images/symbols/lambda.gif" WIDTH="8" HEIGHT="12" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">max pigment was associated with a 'colourless' oil droplet
      with peak measured absorptance below 400 nm. The ultraviolet-sensitive visual
      pigment was paired with a transparent oil droplet which showed no significant
      absorption above 350 nm. A single class of double cone was identified, both
      members of which contained the longwave-sensitive (<IMG
      src="/images/symbols/lambda.gif" WIDTH="8" HEIGHT= "12" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">max 563 nm) visual pigment. The principal member of the
      double cone contained an oil droplet with a topographically variable cut-off
      wavelength below 471 nm; the oil droplet found in the accessory member was only
      measured in the ventral retina and displayed three distinct peaks of absorption
      at approximately 430, 450 and 480 nm. Rod photoreceptors had a <IMG
      src="/images/symbols/lambda.gif" WIDTH="8" HEIGHT="12" ALIGN="BOTTOM"
      NATURALSIZEFLAG="3">max at 503 nm. A new polynomial for fitting visual pigment
      templates to ultraviolet-sensitive visual pigment data is given. Topographic
      density measurements of the different cone classes were made using Nitroblue
      tetrazolium chloride to label selectively bleached photoreceptors. The two
      classes of shortwave-sensitive single cone were more abundant in the dorsal
      retina, and longwave-sensitive single cones were notably less abundant in the
      dorso-temporal region of the retina, which subserves binocular vision.

PMID- 9547324
TI  - Experimental approaches towards interpreting dolphin-stimulated bioluminescence.
AB  - Flow-induced bioluminescence provides a unique opportunity for visualizing the
      flow field around a swimming dolphin. Unfortunately, previous descriptions of
      dolphin-stimulated bioluminescence have been largely anecdotal and often
      conflicting. Most references in the scientific literature report an absence of
      bioluminescence on the dolphin body, which has been invariably assumed to be
      indicative of laminar flow. However, hydrodynamicists have yet to find compelling
      evidence that the flow remains laminar over most of the body. The present study
      integrates laboratory, computational and field approaches to begin to assess the
      utility of using bioluminescence as a method for flow visualization by relating
      fundamental characteristics of the flow to the stimulation of naturally occurring
      luminescent plankton. Laboratory experiments using fully developed pipe flow
      revealed that the bioluminescent organisms identified in the field studies can be
      stimulated in both laminar and turbulent flow when shear stress values exceed
      approximately 0.1 N m-2. Computational studies of an idealized hydrodynamic
      representation of a dolphin (modeled as a 6:1 ellipsoid), gliding at a speed of 2
      m s-1, predicted suprathreshold surface shear stress values everywhere on the
      model, regardless of whether the boundary layer flow was laminar or turbulent.
      Laboratory flow visualization of a sphere demonstrated that the intensity of
      bioluminescence decreased with increasing flow speed due to the thinning of the
      boundary layer, while flow separation caused a dramatic increase in intensity due
      to the significantly greater volume of stimulating flow in the wake. Intensified
      video recordings of dolphins gliding at speeds of approximately 2 m s-1 confirmed
      that brilliant displays of bioluminescence occurred on the body of the dolphin.
      The distribution and intensity of bioluminescence suggest that the flow remained
      attached over most of the body. A conspicuous lack of bioluminescence was often
      observed on the dolphin rostrum and melon and on the leading edge of the dorsal
      and pectoral fins, where the boundary layer is thought to be thinnest. To
      differentiate between effects related to the thickness of the stimulatory
      boundary layer and those due to the latency of the bioluminescence response and
      the upstream depletion of bioluminescence, laboratory and dolphin studies of
      forced separation and laminar-to-turbulent transition were conducted. The
      observed pattern of stimulated bioluminescence is consistent with the hypothesis
      that bioluminescent intensity is directly related to the thickness of the
      boundary layer.

PMID- 9547325
TI  - Cardio-respiratory ontogeny during chronic carbon monoxide exposure in the clawed
      frog Xenopus laevis.
AB  - The present study investigates the ontogeny of cardio-respiratory physiology in
      Xenopus laevis where O2 transport is obstructed. Animals were raised from eggs
      (NF stage 1) to metamorphic climax (NF stage 63), while maintained either in air
      or in chronic 2 kPa CO, which functionally ablates O2 transport by hemoglobin
      (Hb). Whole-animal rate of oxygen consumption (.MO2), whole-body lactate
      concentration, individual mass, heart rate (fh) and stroke volume (Vs) were
      measured. Additionally, cardiac output (.Q) and the ratio of the rate of oxygen
      consumption to the total rate at which oxygen is transported in the blood
      (.MO2/.QO2) were calculated to determine limitations imparted when O2 transport
      is impaired. Our data on early development suggest that the onset of convective
      blood flow occurs prior to the absolute need for convection to supplement
      diffusive transport. Values for .MO2, whole-body lactate concentration, mass and
      fh did not differ significantly between controls and CO-exposed animals. However,
      CO-exposed animals showed a significant (P<0.05) increase in Vs, .MO2/.QO2 and .Q
      compared with controls. These results indicate that limiting blood O2 transport
      is not deleterious to metabolism and development as a whole and that convective
      oxygen transport via Hb is not essential for normal cardiovascular or respiratory
      function during larval development.

PMID- 9547326
TI  - Mechanisms of acid-base regulation in migrant sea lampreys (Petromyzon marinus)
      following exhaustive exercise 
AB  - The life cycle of the sea lamprey (Petromyzon marinus) is characterized by a
      terminal upstream spawning migration that may be associated with brief bursts of
      high-intensity swimming. Such activity usually leads to pronounced blood acid
      base disturbances in fishes, but lampreys rapidly correct these perturbations
      within 1 h. In the present study, patterns of post-exercise H+ excretion (JHnet)
      and ion movements were followed in sea lampreys to test the hypothesis that
      dynamic manipulation of Na+ versus Cl- movements across the animal's body
      surface, presumably at the gills, accounted for the rapid restoration of blood pH
      following exercise. The first hour of post-exercise recovery in sea lampreys was
      associated with marked stimulation of JHnet (equivalent to base uptake), which
      approached -500 micromol kg-1 h-1. After 1 h, JHnet patterns had returned to
      resting rates. Analyses of net Na+ and Cl- movements (JNanet, JClnet) suggested
      that elevated net Cl- losses, which greatly exceeded net Na+ losses, accounted
      for most of the JHnet. Subsequent experiments, using radiotracers (22Na+, 36Cl-),
      indicated that differential increases in Cl- versus Na+ permeability accounted
      for the greater post-exercise Cl- losses and the corresponding stimulation of net
      proton excretion. Finally, metabolic acid budget analyses confirmed our
      hypothesis that rapid excretion of metabolic protons was the primary means used
      by sea lampreys to correct post-exercise extracellular acidosis. <P>

PMID- 9547327
TI  - Proprioceptive contribution to distance estimation by motion parallax in a
      praying mantid 
AB  - The behavioural experiments described here examined, in the praying mantis
      Tenodera sinensis, the manner in which the proprioceptive cervical hair plate
      sensilla are involved in the measurement of the distance to a jump target with
      the aid of motion parallax actively produced by translatory head motion. Various
      combinations of surgical deafferentation of the cervical hair plate sensilla had
      no influence on the linearisation of head motion. However, the measurement of
      relative and absolute distance and the jump frequency were impaired by these
      interventions. From the results, it is concluded that the cervical hair plate
      sensilla are involved in the distance measurement mechanism, probably by allowing
      the nervous system to compare retinal image motion with head motion. <P>

PMID- 9547328
TI  - New paths in human cancer serology.

PMID- 9547329
TI  - The normal counterpart of IgD myeloma cells in germinal center displays
      extensively mutated IgVH gene, Cmu-Cdelta switch, and lambda light chain
      expression.
AB  - Human myeloma are incurable hematologic cancers of immunoglobulin-secreting
      plasma cells in bone marrow. Although malignant plasma cells can be almost
      eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma
      precursor cells persist in an apparently cryptic compartment. Controversy exists
      as to whether myeloma precursor cells are hematopoietic stem cells, pre-B cells,
      germinal center (GC) B cells, circulating memory cells, or plasma blasts. This
      situation reflects what has been a general problem in cancer research for years:
      how to compare a tumor with its normal counterpart. Although several studies have
      demonstrated somatically mutated immunoglobulin variable region genes in multiple
      myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B
      cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin
      features, including a biased lambda light chain expression and a Cmu-Cdelta
      isotype switch. Using surface markers, we have previously isolated a population
      of surface IgM-IgD+CD38+ GC B cells that carry the most impressive somatic
      mutation in their IgV genes. Here we show that this population of GC B cells
      displays the two molecular features of IgD-secreting myeloma cells: a biased
      lambda light chain expression and a C&mu-Cdelta isotype switch. The demonstration
      of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but
      not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma
      and myeloma cells are derived from GCs.

PMID- 9547330
TI  - T cell receptor (TCR) engagement in apoptosis-defective, but interleukin 2 (IL-2)
      producing, T cells results in impaired ZAP70/CD3-zeta association.
AB  - We have previously shown that a tyrosine to leucine replacement in the
      transmembrane region of T cell receptor (TCR)-beta results in a deficient
      induction of CD95-L and apoptosis upon TCR triggering in a transfected T cell
      line. By contrast, interleukin (IL)-2 production and the expression of CD25 and
      CD69 were normally induced. Since the mutation in TCR-beta also resulted in
      impaired association of CD3-zeta, it was proposed that this chain is specifically
      required for the induction of apoptosis. We now show that the deficient induction
      of CD95-L and apoptosis does not derive from a general lower production of second
      messengers, since intracellular Ca2+ fluxes and tyrosine phosphorylation of total
      proteins were elicited at wild-type levels. Unlike in T cell clones stimulated
      with partial agonists, both p21 and p18 forms of tyrosine-phosphorylated CD3-zeta
      were detected, although the overall level of tyrosine-phosphorylated CD3-zeta was
      low. More strikingly, inducible association of ZAP70 to CD3-zeta was strongly
      inhibited, despite a normal induction of ZAP70 tyrosine phosphorylation. Finally,
      ZAP70 was not concentrated near the plasma membrane in the apoptosis-deficient
      cells. These results suggest that CD3-zeta is necessary for engagement of a
      specific signaling pathway leading to CD95-L expression that also needs the
      recruitment of ZAP70.

PMID- 9547331
TI  - T helper 1 (Th1) and Th2 characteristics start to develop during T cell priming
      and are associated with an immediate ability to induce immunoglobulin class
      switching.
AB  - The respective production of specific immunoglobulin (Ig)G2a or IgG1 within 5 d
      of primary immunization with Swiss type mouse mammary tumor virus [MMTV(SW)] or
      haptenated protein provides a model for the development of T helper 1 (Th1) and
      Th2 responses. The antibody-producing cells arise from cognate T cell B cell
      interaction, revealed by the respective induction of Cgamma2a and Cgamma1 switch
      transcript production, on the third day after immunization. T cell proliferation
      and upregulation of mRNA for interferon gamma in response to MMTV(SW) and
      interleukin 4 in response to haptenated protein also starts during this day. It
      follows that there is minimal delay in these responses between T cell priming and
      the onset of cognate interaction between T and B cells leading to class switching
      and exponential growth. The Th1 or Th2 profile is at least partially established
      at the time of the first cognate T cell interaction with B cells in the T zone.
      The addition of killed Bordetella pertussis to the hapten-protein induces
      nonhapten-specific IgG2a and IgG1 plasma cells, whereas the anti-hapten response
      continues to be IgG1 dominated. This indicates that a Th2 response to hapten
      protein can proceed in a node where there is substantial Th1 activity.

PMID- 9547332
TI  - Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated
      with downregulation of its proapoptotic activity and loss of liver toxicity.
AB  - Human Fas ligand (L) (CD95L) and tumor necrosis factor (TNF)-alpha undergo
      metalloproteinase-mediated proteolytic processing in their extracellular domains
      resulting in the release of soluble trimeric ligands (soluble [s]FasL, sTNF
      alpha) which, in the case of sFasL, is thought to be implicated in diseases such
      as hepatitis and AIDS. Here we show that the processing of sFasL occurs between
      Ser126 and Leu127. The apoptotic-inducing capacity of naturally processed sFasL
      was reduced by >1,000-fold compared with membrane-bound FasL, and injection of
      high doses of recombinant sFasL in mice did not induce liver failure. However,
      soluble FasL retained its capacity to interact with Fas, and restoration of its
      cytotoxic activity was achieved both in vitro and in vivo with the addition of
      cross-linking antibodies. Similarly, the marginal apoptotic activity of
      recombinant soluble TNF-related apoptosis-inducing ligand (sTRAIL), another
      member of the TNF ligand family, was greatly increased upon cross-linking. These
      results indicate that the mere trimerization of the Fas and TRAIL receptors may
      not be sufficient to trigger death signals. Thus, the observation that sFasL is
      less cytotoxic than membrane-bound FasL may explain why in certain types of
      cancer, systemic tissue damage is not detected, even though the levels of
      circulating sFasL are high.

PMID- 9547333
TI  - Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a
      novel inhibitory mechanism of HIV infectivity.
AB  - CCR5, a chemokine receptor expressed on T cells and macrophages, is the principal
      coreceptor for M-tropic HIV-1 strains. Recently, we described an NH2-terminal
      modification of the CCR5 ligand regulated on activation, normal T cell expressed
      and secreted (RANTES), aminooxypentane-RANTES (AOP-RANTES), that showed potent
      inhibition of macrophage infection by HIV-1 under conditions where RANTES was
      barely effective. To investigate the mechanism of AOP-RANTES inhibition of HIV
      infectivity we examined the surface expression of CCR5 using a monoclonal anti
      CCR5 antibody, MC-1. We demonstrate that AOP-RANTES rapidly caused >90% decrease
      in cell surface expression of CCR5 on lymphocytes, monocytes/ macrophages, and
      CCR5 transfected Chinese hamster ovary (CHO) cells. RANTES also caused a loss of
      cell surface CCR5, although its effect was less than with AOP-RANTES.
      Significantly, AOP-RANTES inhibited recycling of internalized CCR5 to the cell
      surface, whereas RANTES did not. When peripheral blood mononuclear cells are
      cultured for prolonged periods of time in the presence of RANTES, CCR5 expression
      is comparable to that seen on cells treated with control medium, whereas there is
      no CCR5 surface expression on cells cultured in the presence of AOP-RANTES.
      Immunofluorescence indicated that both AOP-RANTES and RANTES induced
      downmodulation of cell surface CCR5, and that the receptor was redistributed into
      endocytic organelles containing the transferrin receptor. When RANTES was
      removed, the internalized receptor was recycled to the cell surface; however, the
      receptor internalized in the presence of AOP-RANTES was retained in endosomes.
      Using human osteosarcoma (GHOST) 34/CCR5 cells, the potency of AOP-RANTES and
      RANTES to inhibit infection by the M-tropic HIV-1 strain, SF 162, correlated with
      the degree of downregulation of CCR5 induced by the two chemokines. These
      differences between AOP-RANTES and RANTES in their effect on receptor
      downregulation and recycling suggest a mechanism for the potent inhibition of HIV
      infection by AOP-RANTES. Moreover, these results support the notion that receptor
      internalization and inhibition of receptor recycling present new targets for
      therapeutic agents to prevent HIV infection.

PMID- 9547334
TI  - T cell-mediated pathology in two models of experimental colitis depends
      predominantly on the interleukin 12/Signal transducer and activator of
      transcription (Stat)-4 pathway, but is not conditional on interferon gamma
      expression by T cells.
AB  - The requirements for interleukin (IL)-12/signal transducer and activator of
      transcription (Stat)-4 signaling and induction of T cell-specific interferon
      (IFN)-gamma expression in the development of T helper cell (Th)1-type pathology
      were examined in two different models of experimental colitis. In each model,
      abnormal reconstitution of the T cell compartment in immunodeficient mice by
      adoptive cell transfer leads to a wasting syndrome and inflammation of the colon,
      induced by IFN-gamma and tumor necrosis factor (TNF)-alpha-producing T cells. We
      show here that treatment with anti-IL-12 antibodies in one of the models, or
      reconstitution with T cells from Stat-4-deficient (Stat-4(null)) mice in both
      models resulted in a milder disease in the majority of recipient animals,
      compared with those that were left untreated or that had been reconstituted with
      wt cells. Protected mice in each group also harbored lower frequencies of IFN
      gamma-producing T cells than did diseased mice, suggesting that effects on
      wasting and colitis resulted from the attenuation of IFN-gamma expression by T
      cells. To test whether the development of pathogenic T cells in the two colitis
      models was directly dependent on T cell-specific IFN-gamma expression, IFN
      gammanull donors were used for T cell reconstitution in each system.
      Surprisingly, large numbers of IFN-gammanull-reconstituted mice developed wasting
      and colitis, which in many cases was of comparable severity to that seen in
      animals reconstituted with wt cells. Furthermore, T cells from these animals
      expressed TNF-alpha, demonstrating that they had retained the ability to produce
      another proinflammatory cytokine. Taken together, these results demonstrate that
      in some forms of chronic experimental colitis the development of pathogenic T
      cells is influenced predominantly, though not exclusively, by IL-12 via the
      actions of Stat-4 proteins. Furthermore, our data suggest that in the models of
      colitis studied here the effects of IL-12/Stat-4 or other Th1 promoting pathways
      are not limited to the induction of IFN-gamma gene expression in T lymphocytes.

PMID- 9547336
TI  - CD3 ligation on immature thymocytes generates antagonist-like signals appropriate
      for CD8 lineage commitment, independently of T cell receptor specificity.
AB  - The signals that direct differentiation of T cells to the CD4 or CD8 lineages in
      the thymus remain poorly understood. Although it has been relatively easy to
      direct differentiation of CD4 single positive (CD4+) cells using combinations of
      antibodies and pharmacological agents that mimic receptor engagements, equivalent
      stimuli do not induce efficient maturation of CD8+ cells. Here we report that,
      irrespective of the MHC-restriction specificity of the TCR, differentiation of
      mature CD8+ thymocytes can be induced by ligation of CD3 polypeptides on immature
      thymocytes with a F(ab')2 reagent (CD3fos-F(ab')2). The tyrosine phosphorylation
      patterns stimulated by CD3fos-F(ab')2 have been shown to resemble those delivered
      to mature T cells by antagonist peptides, which are known to direct positive
      selection of CD8+ cells, and we can show that this reagent exhibits potent
      antagonistic-like activity for primary T cell responses. Our results suggest a
      distinction in the signals that specify lineage commitment in the thymus. We
      present a model of thymocyte differentiation that proposes that the relative
      balance of signals delivered by TCR engagement and by p56lck activation is
      responsible for directing commitment to the CD8 or CD4 lineages.

PMID- 9547335
TI  - Involvement of Bruton's tyrosine kinase in FcepsilonRI-dependent mast cell
      degranulation and cytokine production.
AB  - We investigated the role of Bruton's tyrosine kinase (Btk) in FcepsilonRI
      dependent activation of mouse mast cells, using xid and btk null mutant mice.
      Unlike B cell development, mast cell development is apparently normal in these
      btk mutant mice. However, mast cells derived from these mice exhibited
      significant abnormalities in FcepsilonRI-dependent function. xid mice primed with
      anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early
      phase and severely blunted late-phase anaphylactic reactions in response to
      antigen challenge in vivo. Consistent with this finding, cultured mast cells
      derived from the bone marrow cells of xid or btk null mice exhibited mild
      impairments in degranulation, and more profound defects in the production of
      several cytokines, upon FcepsilonRI cross-linking. Moreover, the transcriptional
      activities of these cytokine genes were severely reduced in FcepsilonRI
      stimulated btk mutant mast cells. The specificity of these effects of btk
      mutations was confirmed by the improvement in the ability of btk mutant mast
      cells to degranulate and to secrete cytokines after the retroviral transfer of
      wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral
      transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the
      ability of btk mutant mast cells to secrete mediators. Taken together, these
      results demonstrate an important role for Btk in the full expression of
      FcepsilonRI signal transduction in mast cells.

PMID- 9547337
TI  - The permeability transition pore complex: a target for apoptosis regulation by
      caspases and bcl-2-related proteins.
AB  - Early in programmed cell death (apoptosis), mitochondrial membrane permeability
      increases. This is at least in part due to opening of the permeability transition
      (PT) pore, a multiprotein complex built up at the contact site between the inner
      and the outer mitochondrial membranes. The PT pore has been previously implicated
      in clinically relevant massive cell death induced by toxins, anoxia, reactive
      oxygen species, and calcium overload. Here we show that PT pore complexes
      reconstituted in liposomes exhibit a functional behavior comparable with that of
      the natural PT pore present in intact mitochondria. The PT pore complex is
      regulated by thiol-reactive agents, calcium, cyclophilin D ligands (cyclosporin A
      and a nonimmunosuppressive cyclosporin A derivative), ligands of the adenine
      nucleotide translocator, apoptosis-related endoproteases (caspases), and Bcl-2
      like proteins. Although calcium, prooxidants, and several recombinant caspases
      (caspases 1, 2, 3, 4, and 6) enhance the permeability of PT pore-containing
      liposomes, recombinant Bcl-2 or Bcl-XL augment the resistance of the
      reconstituted PT pore complex to pore opening. Mutated Bcl-2 proteins that have
      lost their cytoprotective potential also lose their PT modulatory capacity. In
      conclusion, the PT pore complex may constitute a crossroad of apoptosis
      regulation by caspases and members of the Bcl-2 family.

PMID- 9547338
TI  - Extent of laminin-5 assembly and secretion effect junctional epidermolysis
      bullosa phenotype.
AB  - Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering
      disease with both lethal and nonlethal forms, with most patients shown to have
      defects in laminin-5. We analyzed the location of mutations, gene expression
      levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB
      patients to determine how the type of genetic lesion influences the
      pathophysiology of JEB. Mutations within laminin-5 genes were diversely located,
      with the most severe forms of JEB correlating best with premature termination
      codons, rather than mapping to any particular protein domain. In all six JEB
      patients, the laminin-5 assembly intermediates we observed were as predicted by
      our previous work indicating that the alpha3beta3gamma2 heterotrimer assembles
      intracellularly via a beta3gamma2 heterodimer intermediate. Since assembly
      precedes secretion, mutations that disrupt protein-protein interactions needed
      for assembly are predicted to limit the secretion of laminin-5, and likely to
      interfere with function. However, our data indicate that typically the most
      severe mutations diminish mRNA stability, and serve as functional null alleles
      that block chain assembly by resulting in either a deficiency (in the nonlethal
      mitis variety) or a complete absence (in lethal Herlitz-JEB) of one of the chains
      needed for laminin-5 heterotrimer assembly.

PMID- 9547339
TI  - Identification of a human enterocyte lipoxin A4 receptor that is regulated by
      interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha
      induced IL-8 release.
AB  - Epithelial cells of the alimentary tract play a central role in mucosal
      immunophysiology. Pathogens and/or agonists that interact with mucosal surfaces
      often elicit epithelial responses that upregulate inflammation. Therefore, it was
      of interest to explore potential epithelial targeted antiinflammatory signals.
      Here we identified and sequenced a human enterocyte lipoxin (LX) A4 [5(S),
      6(R),15(S)-trihydroxy-7,9,13-trans-11-cis eicosatetraenoic acid] receptor, and
      demonstrate that transcription of this receptor was controlled by cytokines, of
      which lymphocyte-derived interleukin (IL)-13 and interferon gamma were the most
      potent. When lipoxins and LXA4 stable analogs were evaluated for enterocyte
      functional as well as immune responses, lipoxins sharply inhibited TNF-alpha
      induced IL-8 release but did not alter either barrier function or agonist
      stimulated chloride secretion. 15R/S-methyl-LXA4 and 16-phenoxy-LXA4 each
      attenuated (IC50 approximately 10 nM) IL-8 release. Cyclooxygenase (COX) II is
      emerging as an important component in wound healing and proliferation in
      intestinal epithelia and when acetylated by acetylsalicylic acid (aspirin)
      initiates the biosynthesis of a LXA4 receptor ligand. We therefore determined
      whether colonic cell lines (HT-29 Cl.19A, Caco-2, or T84) express the COX II
      isozyme. Results for RT-PCR and Western blot analysis showed that COX I as well
      as an IL-1beta- and TNF-alpha-inducible COX II are expressed in HT-29 Cl.19A. In
      addition, aspirin-treated enterocytes generated 15R-HETE, a precursor of 15-epi
      LXA4 biosynthesis, whose potent bioactions were mimicked by the stable analog
      15R/S-methyl-LXA4. Taken together, these results identify an endogenous pathway
      for downregulating mucosal inflammatory events and suggest a potential
      therapeutic benefit for LXA4 stable analogs.

PMID- 9547340
TI  - Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67
      antigen.
AB  - We investigated CD4+ and CD8+ T cell turnover in both healthy and HIV-1-infected
      adults by measuring the nuclear antigen Ki-67 specific for cell proliferation.
      The mean growth fraction, corresponding to the expression of Ki-67, was 1.1% for
      CD4(+) T cells and 1.0% in CD8(+) T cells in healthy adults, and 6.5 and 4.3% in
      HIV-1-infected individuals, respectively. Analysis of CD45RA+ and CD45RO+ T cell
      subsets revealed a selective expansion of the CD8+ CD45RO+ subset in HIV-1
      positive individuals. On the basis of the growth fraction, we derived the
      potential doubling time and the daily turnover of CD4+ and CD8+ T cells. In HIV-1
      infected individuals, the mean potential doubling time of T cells was five times
      shorter than that of healthy adults. The mean daily turnover of CD4+ and CD8+ T
      cells in HIV-1-infected individuals was increased 2- and 6-fold, respectively,
      with more than 40-fold interindividual variation. In patients with <200 CD4+
      counts, CD4+ turnover dropped markedly, whereas CD8+ turnover remained elevated.
      The large variations in CD4+ T cell turnover might be relevant to individual
      differences in disease progression.

PMID- 9547341
TI  - Impaired interleukin 4 signaling in T helper type 1 cells.
AB  - Cluster of differentation (CD)4+ T helper cells (Th)1s fail to produce
      interleukin (IL)-4. Even if restimulated in the presence of IL-4, a condition
      that induces IL-4-producing capacity in naive CD4+ T cells, Th1s fail to become
      IL-4 producers. We report that Th1 cells have a major impairment in IL-4
      signaling. When compared to both Th2s and naive T cells, they display a striking
      diminution in phosphorylation of Stat6. They also show reduced phosphorylation of
      Janus kinase (JAK)-3 and insulin receptor substrate (IRS)-2 when compared to
      Th2s. Stat6 and JAK-3 are present in equivalent amounts in Th1s and Th2s, but IRS
      2 protein levels are much lower in Th1s than in Th2s. Altered sensitivity to IL
      4, the major inducer of the Th2 phenotype, may explain the stability of the Th1
      state.

PMID- 9547342
TI  - CD40 ligand is not essential for induction of type 1 cytokine responses or
      protective immunity after primary or secondary infection with histoplasma
      capsulatum.
AB  - The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]
      gamma) has been shown to be important in mediating protection against many
      intracellular infections including Histoplasma capsulatum. Costimulatory
      molecules such as CD40 ligand (CD40L) have been shown to be a central regulator
      of type 1 responses in vivo. To study the role of CD40L in mediating protection
      against infection with H. capsulatum, CD40L-deficient (CD40L-/-) and CD40L+/+
      mice were infected with H. capsulatum and assessed for various parameters. After
      a lethal challenge of H. capsulatum, CD40L-/- mice were not substantially
      different from CD40L+/+ mice in terms of mortality, fungal burden, or production
      of IFN-gamma, IL-12, nitric oxide, or tumor necrosis factor alpha. Moreover,
      CD40L-/- mice treated with anti-IFN-gamma or anti-IL-12 at the time of infection
      had accelerated mortality, providing further evidence that IL-12 and IFN-gamma
      are produced in vivo in the absence of CD40L. In addition, CD40L-/- mice infected
      with a sublethal dose of H. capsulatum survived infection, whereas all mice
      infected with the same dose and treated with anti-IFN-gamma had accelerated
      mortality, demonstrating that IFN-gamma but not CD40L was essential for primary
      immunity to H. capsulatum infection. Interestingly, depletion of either CD4+ or
      CD8+ T cells resulted in accelerated mortality in CD40L-/- mice, suggesting a
      critical role for these cells in response to infection. Finally, CD40L-/- mice
      initially infected with a sublethal dose of H. capsulatum were protected from
      secondary infection with a lethal dose of H. capsulatum, demonstrating that CD40L
      is not required for the maintenance of memory immunity.

PMID- 9547343
TI  - B-1 cell development: evidence for an uncommitted immunoglobulin (Ig)M+ B cell
      precursor in B-1 cell differentiation.
AB  - Murine phosphatidyl choline (PtC)-specific B cells in normal mice belong
      exclusively to the B-1 subset. Analysis of anti-PtC (VH12 and VH12/Vkappa4)
      transgenic (Tg) mice indicates that exclusion from B-0 (also known as B-2) occurs
      after immunoglobulin gene rearrangement. This predicts that PtC-specific B-0
      cells are generated, but subsequently eliminated by either apoptosis or
      differentiation to B-1. To investigate the mechanism of exclusion, PtC-specific B
      cell differentiation was examined in mice expressing the X-linked
      immunodeficiency (xid) mutation. xid mice lack functional Bruton's tyrosine
      kinase (Btk), a component of the B cell receptor signal transduction pathway, and
      are deficient in B-1 cell development. We find in C57BL/ 6.xid mice that VH12 pre
      BII cell selection is normal and that PtC-specific B cells undergo modest clonal
      expansion. However, the majority of splenic PtC-specific B cells in anti-PtC
      Tg/xid mice are B-0, rather than B-1 as in their non-xid counterparts. These data
      indicate that PtC-specific B-0 cell generation precedes segregation as predicted,
      and that Btk function is required for efficient segregation to B-1. Since xid
      mice exhibit defective B cell differentiation, not programmed cell death, these
      data are most consistent with an inability of PtC-specific B-0 cells to convert
      to B-1 and a single B cell lineage.

PMID- 9547344
TI  - Tolerization of anti-Galalpha1-3Gal natural antibody-forming B cells by induction
      of mixed chimerism.
AB  - Xenotransplantation could overcome the severe shortage of allogeneic organs, a
      major factor limiting organ transplantation. Unfortunately, transplantation of
      organs from pigs, the most suitable potential donor species, results in
      hyperacute rejection in primate recipients, due to the presence of anti-Galalpha1
      3Gal (Gal) natural antibodies (NAbs) in their sera. We evaluated the ability to
      tolerize anti-Gal NAb-producing B cells in alpha1,3-galactosyltransferase
      knockout (GalT KO) mice using bone marrow transplantation (BMT) from GalT+/+ wild
      type (WT) mice. Lasting mixed chimerism was achieved in KO mice by
      cotransplantation of GalT KO and WT marrow after lethal irradiation. The levels
      of anti-Gal NAb in sera of mixed chimeras were reduced markedly 2 wk after BMT,
      and became undetectable at later time points. Immunization with Gal+/+ xenogeneic
      cells failed to stimulate anti-Gal antibody production in mixed chimeras, whereas
      the production of non-Gal-specific antixenoantigen antibodies was stimulated. An
      absence of anti-Gal-producing B cells was demonstrated by enzyme-linked
      immunospot assays in mixed KO + WT --> KO chimeras. Thus, mixed chimerism
      efficiently induces anti-Gal-specific B cell tolerance in addition to T cell
      tolerance, providing a single approach to overcoming both the humoral and the
      cellular immune barriers to discordant xenotransplantation.

PMID- 9547345
TI  - A double-edged kinase Lyn: a positive and negative regulator for antigen receptor
      mediated signals.
AB  - B cells from young lyn-/- mice are hyperresponsive to anti-IgM-induced
      proliferation, suggesting involvement of Lyn in negative regulation of B cell
      antigen receptor (BCR)-mediated signaling. Here we show that tyrosine
      phosphorylation of FcgammaRIIB and CD22 coreceptors, which are important for
      feedback suppression of BCR-induced signaling, was severely impaired in lyn-/- B
      cells upon their coligation with the BCR. Hypophosphorylation on tyrosine
      residues of these molecules resulted in failure of recruiting the tyrosine
      phosphatase SHP-1 and inositol phosphatase SHIP, SH2-containing potent inhibitors
      of BCR-induced B cell activation, to the coreceptors. Consequently, lyn-/- B
      cells exhibited defects in suppressing BCR-induced Ca2+ influx and proliferation.
      Thus, Lyn is critically important in tyrosine phosphorylation of the coreceptors,
      which is required for feedback suppression of B cell activation.

PMID- 9547346
TI  - A survey of the humoral immune response of cancer patients to a panel of human
      tumor antigens.
AB  - Evidence is growing for both humoral and cellular immune recognition of human
      tumor antigens. Antibodies with specificity for antigens initially recognized by
      cytotoxic T lymphocytes (CTLs), e.g., MAGE and tyrosinase, have been detected in
      melanoma patient sera, and CTLs with specificity for NY-ESO-1, a cancer-testis
      (CT) antigen initially identified by autologous antibody, have recently been
      identified. To establish a screening system for the humoral response to
      autoimmunogenic tumor antigens, an enzyme-linked immunosorbent assay (ELISA) was
      developed using recombinant NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and
      tyrosinase proteins. A survey of sera from 234 cancer patients showed antibodies
      to NY-ESO-1 in 19 patients, to MAGE-1 in 3, to MAGE-3 in 2, and to SSX2 in 1
      patient. No reactivity to these antigens was found in sera from 70 normal
      individuals. The frequency of NY-ESO-1 antibody was 9.4% in melanoma patients and
      12.5% in ovarian cancer patients. Comparison of tumor NY-ESO-1 phenotype and NY
      ESO-1 antibody response in 62 stage IV melanoma patients showed that all patients
      with NY-ESO-1(+) antibody had NY-ESO-1(+) tumors, and no patients with NY-ESO-1(
      ) tumors had NY-ESO-1 antibody. As the proportion of melanomas expressing NY-ESO
      1 is 20-40% and only patients with NY-ESO-1(+) tumors have antibody, this would
      suggest that a high percentage of patients with NY-ESO-1(+) tumors develop an
      antibody response to NY-ESO-1.

PMID- 9547348
TI  - Activation by diverse xenochemicals of the 51-base pair phenobarbital-responsive
      enhancer module in the CYP2B10 gene.
AB  - By extending previous studies of the phenobarbital (PB)-responsive 132-base pair
      (bp) enhancer sequence in the CYP2B10 gene, we have delimited a 51-bp enhancer
      element that is fully inducible by PB in mouse primary hepatocytes. Sixteen
      structurally unrelated phenobarbital-type inducers activated the 51-bp enhancer
      element in transient transfection assays. The results thus indicate that most PB
      type inducers, if not all inducers, increase the transcription of the CYP2B10
      gene by activating this 51-bp element, now designated PB-responsive enhancer
      module or PBREM.

PMID- 9547347
TI  - Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for
      paired immunoglobulin-like receptor B (PIR-B)-mediated inhibitory signal.
AB  - Paired immunoglobulin-like receptor B (PIR-B) (p91) molecule has been proposed to
      function as an inhibitory receptor in B cells and myeloid lineage cells. We
      demonstrate here that the cytoplasmic region of PIR-B is capable of inhibiting B
      cell activation. Mutational analysis of five cytoplasmic tyrosines indicate that
      tyrosine 771 in the motif VxYxxL plays the most crucial role in mediating the
      inhibitory signal. PIR-B-mediated inhibition was markedly reduced in the SH2
      containing protein tyrosine phosphatases SHP-1 and SHP-2 double-deficient DT40 B
      cells, whereas this inhibition was unaffected in the inositol polyphosphate 5'
      phosphatase SHIP-deficient cells. These data demonstrate that PIR-B can
      negatively regulate B cell receptor activation and that this PIR-B-mediated
      inhibition requires redundant functions of SHP-1 and SHP-2.

PMID- 9547349
TI  - Involvement of c-Jun NH2-terminal kinase activation and c-Jun in the induction of
      apoptosis by the ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3
      phosphocholine.
AB  - The ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET
      18-OCH3; edelfosine) is a potent inducer of apoptosis in human tumor cells. We
      show that ET-18-OCH3-induced apoptosis is associated with activation of the c-Jun
      NH2-terminal kinase (JNK) signaling. The addition of ET-18-OCH3 to distinct human
      leukemic cells (HL-60, U937, and Jurkat), which undergo rapid apoptosis on
      treatment with ET-18-OCH3, induced a dramatic and sustained increase in the of c
      jun mRNA level that was associated with activation of activator protein-1
      transcription factor. We found that ET-18-OCH3 induced a persistent activation of
      JNK in HL-60 cells that was detected before the onset of apoptosis, the latter
      being assessed by DNA fragmentation and by the appearance of phosphatidylserine
      on the external leaflet of the plasma membrane. The inductions of JNK after HL-60
      monocyte/macrophage differentiation and ET-18-OCH3-mediated apoptosis were
      distinguished by the different activation patterns, transient versus persistent,
      respectively. ET-18-OCH3 analogues unable to induce apoptosis failed to activate
      JNK. ET-18-OCH3-dependent JNK activation was not detected in K562 cells, which
      did not undergo apoptosis on treatment with ET-18-OCH3. Phorbol myristate acetate
      inhibited both ET-18-OCH3-induced apoptosis and sustained JNK activation; thus,
      persistent JNK activation by ET-18-OCH3 is associated with the capacity of this
      ether phospholipid to induce apoptosis. Furthermore, antisense oligonucleotides
      directed against c-jun blocked ET-18-OCH3-induced apoptosis, indicating a role
      for c-Jun in this apoptotic response. These data indicate that JNK activation and
      c-Jun are involved in the induction of apoptosis by ET-18-OCH3.

PMID- 9547350
TI  - A G protein beta gamma dimer-mediated pathway contributes to mitogen-activated
      protein kinase activation by thyrotropin-releasing hormone receptors in
      transfected COS-7 cells.
AB  - Activation of mitogen-activated protein kinase (MAPK) is induced by adding
      thyrotropin-releasing hormone (TRH) to COS-7 cells cotransfected with TRH
      receptors and an epitope-tagged MAPK. Long term treatment of the cells with
      pertussis toxin has no effect on TRH-induced MAPK activation. Incubation of the
      cells with the protein kinase C (PKC) inhibitor GF109203X causes an almost
      complete inhibition of MAPK activation by the PKC activator phorbol-12-myristate
      13-acetate. In contrast, only approximately 50% of the TRH-induced MAPK activity
      is inhibited by GF109203X, indicating that activation of MAPK by TRH is only
      partially dependent on PKC. The inhibitory effect of GF109203X is additive with
      that of p21(N17ras), a dominant negative mutant of p21(ras) that exerts little
      effect on PKC-dependent MAPK activation by phorbol-12-myristate-13-acetate. The
      TRH-induced activation of MAPK also is inhibited partially by overexpression of
      transducin alpha subunits (alpha t), an agent known to sequester free G protein
      beta gamma dimers. However, the inhibitory potency of alpha t on TRH-induced
      activation is about half of that obtained in cells transfected with m2 muscarinic
      receptors, which activate MAPK exclusively through beta gamma dimers. The effect
      of alpha t is also additive with that of GF109203X but not with that of
      p21(N17ras). MAPK activation is not induced by the constitutively active form of
      G alpha q due to an inhibitory effect of its expression at a step downstream of
      that at which PKC-dependent and -independent routes to MAPK converge. Our results
      demonstrate that TRH receptors activate MAPK by a pathway only partially
      dependent on PKC activity. Furthermore, they indicate that beta gamma dimers of a
      pertussis and cholera toxin-insensitive G protein are involved in the PKC
      independent fraction of the dual signaling route to MAPK initiated in the TRH
      receptor.

PMID- 9547351
TI  - Aryl hydrocarbon receptor-dependent suppression by 2,3,7, 8-tetrachlorodibenzo-p
      dioxin of IgM secretion in activated B cells.
AB  - The immune system has been identified as a sensitive target for the toxic effects
      produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Furthermore, the B cell
      has been identified as a sensitive cellular target of TCDD by previous cell-type
      fractionation studies from this laboratory. The mechanism responsible for the
      immunotoxic effects produced by TCDD is unclear; however, many of the biological
      effects of TCDD are thought to be mediated by the aryl hydrocarbon receptor
      (AhR). Here, we describe two B cell lines that differ considerably in their
      expression of the AhR and in their sensitivity to TCDD. Our results demonstrated
      a marked expression of the AhR protein in the CH12.LX B cell line but not in the
      BCL-1 B cell line. Transcripts for the AhR were not detected by reverse
      transcriptase-polymerase chain reaction in the BCL-1 cells. The AhR nuclear
      translocator (ARNT) protein was highly expressed in both cell lines. In addition,
      the AhR and ARNT are functional in CH12.LX cells as demonstrated by TCDD-induced
      CYP1A1 induction. TCDD did not induce CYP1A1 in BCL-1 cells. Furthermore, TCDD
      treatment resulted in suppression of lipopolysaccharide (LPS)-induced IgM
      secretion in CH12.LX cells. Conversely, TCDD-induced inhibition of IgM secretion
      was not demonstrated in LPS-stimulated BCL-1 cells, implicating a role for the
      AhR in the inhibition of B cell effector function. LPS-induced differentiation of
      the CH12.LX cells also resulted in a marked induction of Ahr expression which was
      not induced in LPS-stimulated BCL-1 cells. These studies have implicated the AhR
      as a critical factor in TCDD-induced inhibition of IgM secretion and have
      demonstrated an induction of AhR gene and protein expression after B cell
      activation.

PMID- 9547352
TI  - Activation of protein kinase C alpha and/or epsilon enhances transcription of the
      human endothelial nitric oxide synthase gene.
AB  - In primary human umbilical vein endothelial cells (HUVECs), incubation with
      phorbol-12-myristate-13-acetate (PMA) enhanced basal and bradykinin-stimulated
      nitric oxide production. In the HUVEC-derived cell line EA.hy 926, PMA and
      phorbol-12,13-dibutyrate stimulated endothelial nitric oxide synthase (NOS III)
      mRNA expression in a concentration- and time-dependent manner. Maximal mRNA
      expression (3.3-fold increase) was observed after 18 hr. NOS III protein and
      activity were increased to a similar extent. The specific protein kinase C (PKC)
      inhibitors bisindolylmaleimide I (1 microM), Go 6976 [12-(2 cyanoethyl)-6,7,12,
      13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo-[3, 4-c]carbazole] (1
      microM), Ro-31-8220 [3-[1-[3(amidinothio)propyl-1H-inoyl-3-yl]3-(1-methyl-1H-
      indoyl-3-yl) maleimide methane sulfonate] (1 microM), and chelerythrine (3
      microM) did not change NOS III expression when applied alone, but they all
      prevented the up-regulation of NOS III mRNA produced by PMA. Of the PKC isoforms
      expressed in EA.hy 926 cells (alpha, beta I, delta, epsilon, eta, zeta, lambda,
      and mu), only PKC alpha and PKC epsilon showed changes in protein expression
      after PMA treatment. Incubation of EA.hy 926 cells with PMA for 2-6 hr resulted
      in a translocation of PKC alpha and PKC epsilon from the cytosol to the cell
      membrane, indicating activation of these isoforms. After 24 hr of PMA incubation,
      both isoforms were down-regulated. The time course of activation and down
      regulation of these two PKC isoforms correlated well with the PMA-stimulated
      increase in NOS III expression. When human endothelial cells (ECV 304 or EA.hy
      926) were transiently or stably transfected with a 3.5-kb fragment of the human
      NOS III promoter driving a luciferase reporter gene, PMA stimulated promoter
      activity up to 2.5-fold. On the other hand, PMA did not change the stability of
      the NOS III mRNA. These data indicate that stimulation of PKC alpha, PKC epsilon,
      or both by active phorbol esters represents an efficacious pathway activating the
      human NOS III promoter in human endothelium.

PMID- 9547353
TI  - Cytotoxicity and apoptosis produced by cytochrome P450 2E1 in Hep G2 cells.
AB  - Two Hep G2 subclones overexpressing CYP2E1 were established with the use of
      transfection and limited dilution screening techniques. The Hep G2-CI2E1-43 and 
      47 (E47) cells (transduced Hep G2 subclones that overexpress CYP2E1) grew at a
      slower rate than parental Hep G2 cells or control subclones that do not express
      CYP2E1, but remained fully viable. When GSH synthesis was inhibited by treatment
      with buthionine sulfoximine, GSH levels rapidly declined in E47 cells but not
      control cells, which is most likely a reflection of CYP2E1-catalyzed formation of
      reactive oxygen species. Under these conditions of GSH depletion, cytotoxicity
      and apoptosis were found only with the E47 cells. Low levels of lipid
      peroxidation were found in the E47 cells, which became more pronounced after GSH
      depletion. The antioxidants vitamin E, vitamin C, or trolox prevented the lipid
      peroxidation as well as the cytotoxicity and apoptosis, as did transfection with
      plasmid containing antisense CYP2E1 or overexpression of Bcl-2. Levels of ATP
      were lower in E47 cells because of damage to mitochondrial complex I. When GSH
      was depleted, oxygen uptake was markedly decreased with all substrates in the E47
      extracts. Vitamin E completely prevented the decrease in oxygen uptake. Under
      conditions of CYP2E1 overexpression, two modes of CYP2E1-dependent toxicity can
      be observed in Hep G2 cells: a slower growth rate when cellular GSH levels are
      maintained and a loss of cellular viability when cellular GSH levels are
      depleted. Elevated lipid peroxidation plays an important role in the CYP2E1
      dependent toxicity and apoptosis. This direct toxicity of overexpressed CYP2E1
      may reflect the ability of this enzyme to generate reactive oxygen species even
      in the absence of added metabolic substrate.

PMID- 9547354
TI  - Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4
      methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient
      mice.
AB  - The sodium-dependent, high affinity serotonin [5-hydroxytryptamine (5-HT)]
      transporter (5-HTT) provides the primary mechanism for inactivation of 5-HT after
      its release into the synaptic cleft. To further evaluate the function of the 5
      HTT, the murine gene was disrupted by homologous recombination. Despite evidence
      that excess extracellular 5-HT during embryonic development, including that
      produced by drugs that inhibit the 5-HTT, may lead to severe craniofacial and
      cardiac malformations, no obvious developmental phenotype was observed in the 5
      HTT-/- mice. High affinity [3H]5-HT uptake was completely absent in 5-HTT-/-
      mice, confirming a physiologically effective knockout of the 5-HTT gene. 5-HTT
      binding sites labeled with [125I] 3 beta-(4'-iodophenyl)tropan-2 beta-carboxylic
      acid methyl ester were reduced in a gene dose-dependent manner, with no
      demonstrable binding in 5-HTT-/- mutants. In adult 5-HTT-/- mice, marked
      reductions (60-80%) in 5-HT concentrations were measured in several brain
      regions. While (+)-amphetamine-induced hyperactivity did not differ across
      genotypes, the locomotor enhancing effects of (+)-3, 4
      methylenedioxymethamphetamine, a substituted amphetamine that releases 5-HT via a
      transporter-dependent mechanism, was completely absent in 5-HTT-/- mutants.
      Together, these data suggest that the presence of a functional 5-HTT is essential
      for brain 5-HT homeostasis and for 3,4-methylenedioxymethamphetamine-induced
      hyperactivity.

PMID- 9547355
TI  - Differences among type I, II, and III inositol-1,4,5-trisphosphate receptors in
      ligand-binding affinity influence the sensitivity of calcium stores to inositol
      1,4,5-trisphosphate.
AB  - Type I, II, and III inositol-1,4,5-trisphosphate (InsP3) receptors are expressed
      selectively in different cell lines and tissues. We examined whether type I, II,
      and III InsP3 receptors differ in ligand-binding affinity and whether such
      differences influence the sensitivity of Ca2+ stores to InsP3. Initially, SH-SY5Y
      human neuroblastoma cells, AR4-2J rat pancreatoma cells, and RINm5F rat
      insulinoma cells were studied because these cells express predominantly (>85%)
      type I, II, and III receptors, respectively. Immunopurification of receptors from
      these cell lines and measurement of InsP3 binding revealed that the rank order of
      affinity for InsP3 was type I > type II > type III (binding sites were half
      maximally saturated at 1.5, 2.5, and 22.4 nM InsP3, respectively). Examination of
      Ca2+ store mobilization in permeabilized cells showed that InsP3 was equipotent
      in SH-SY5Y and AR4-2J cells but was approximately 5-fold less potent in RINm5F
      cells. In contrast, Ca2+ uptake and InsP3-independent Ca2+ release were very
      similar in the three cell types. The binding affinity of InsP3 in permeabilized
      SH-SY5Y, AR4-2J, and RINm5F cells correlated well with its potency as a Ca2+
      mobilizing agent and with binding affinity to immunopurified type I, II, and III
      receptors. Thus, InsP3 receptor binding affinity seems to influence the potency
      of InsP3 as a Ca2+-mobilizing agent. Finally, immunopurification of type I, II,
      and III receptors from rat tissues revealed that the affinity differences seen in
      receptors purified from cultured cells are paralleled in vivo. In combination,
      the data from cell lines and rat tissues reveal that type I, II, and III
      receptors bind InsP3 with Kd values of approximately 1, approximately 2, and
      approximately 40 nM, respectively, and that the selective expression of a
      particular receptor type will influence the sensitivity of cellular Ca2+ stores
      to InsP3.

PMID- 9547356
TI  - Oxidative stress increases A1 adenosine receptor expression by activating nuclear
      factor kappa B.
AB  - The A1 adenosine receptor (A1AR) contributes to the cytoprotective action of
      adenosine under conditions known to generate reactive oxygen species (ROS).
      Pharmacological manipulation of A1AR expression has been shown to modulate this
      cytoprotective role. In this study, we provide evidence that ROS generated could
      increase the expression of the A1AR and thereby offset the detrimental effects of
      ROS. Incubation of DDT1MF-2 smooth muscle cells with ROS-generating
      chemotherapeutic agents, such as cisplatin (2.5 microM) or H2O2 (10 microM),
      elicited an increase in A1AR expression within 24 hr. The induction by H2O2 was
      reduced by the ROS scavenger catalase but not superoxide dismutase. Inhibition of
      nuclear factor kappa B (NF kappa B) by pyrrolidine dithiocarbamate (200 microM),
      dexamethasone (100 nM), or genistein (1 microM) abrogated the cisplatin-mediated
      increase in A1AR. Cisplatin promoted rapid translocation of NF kappa B (but not
      AP-1) to the nucleus, as detected by electrophoretic mobility shift assays and by
      Western blotting. A putative NF kappa B sequence in the A1AR promoter effectively
      competed with labeled kappa B probe for binding in nuclear preparations derived
      from DDT1MF-2 cells. Transient transfection of DDT1MF-2 cells with the A1AR
      promoter coupled to firefly luciferase reporter gene led to cisplatin-inducible
      and pyrrolidine dithiocarbamate-sensitive luciferase activity, suggesting the
      presence of functional NF kappa B binding site(s) in the A1AR promoter sequence.
      Treatment of cells with (R)-phenylisopropyladenosine (1 microM), an agonist of
      the A1AR, reduced cisplatin-mediated lipid peroxidation, which was reversed after
      blockade of the A1AR. These data suggest that ROS can increase the expression of
      the A1AR by activating NF kappa B regulatory site(s) on this gene and thereby
      enhance the cytoprotective role of adenosine.

PMID- 9547357
TI  - (-)-CGP 12177 causes cardiostimulation and binds to cardiac putative beta 4
      adrenoceptors in both wild-type and beta 3-adrenoceptor knockout mice.
AB  - Some blockers of beta1- and beta2-adrenoceptors cause cardiostimulant effects
      through an atypical beta-adrenoceptor (putative beta4-adrenoceptor) that
      resembles the beta3-adrenoceptor. It is likely but not proven that the putative
      beta4-adrenoceptor is genetically distinct from the beta3-adrenoceptor. We
      therefore investigated whether or not the cardiac atypical beta-adrenoceptor
      could mediate agonist effects in mice lacking a functional beta3-adrenoceptor
      gene (beta3 KO). (-)-CGP 12177, a beta1- and beta2-adrenoceptor blocker that
      causes agonist effects through both beta3-adrenoceptors and cardiac putative
      beta4-adrenoceptors, caused cardiostimulant effects that were not different in
      atria from wild-type (WT) mice and beta3 KO mice. The effects of (-)-CGP 12177
      were resistant to blockade by (-)-propranolol (200 nM) but were blocked by (-)
      bupranolol (1 microM) with an equilibrium dissociation constant of 15 nM in WT
      and 17 nM in beta3 KO. (-)-[3H]CGP 12177 labeled a similar density of the
      putative beta4-adrenoceptor in ventricular membranes from the hearts of both WT
      (Bmax = 52 fmol/mg protein) and beta3 KO (Bmax = 53 fmol/mg protein) mice. The
      affinity of (-)-[3H]CGP 12177 for the cardiac putative beta4-adrenoceptor was not
      different between WT (Kd = 46 nM) and beta3 KO (Kd= 40 nM). These results provide
      definitive evidence that the cardiac putative beta4-adrenoceptor is distinct from
      the beta3-adrenoceptor.

PMID- 9547358
TI  - Suppression of interleukin-2 by the putative endogenous cannabinoid 2-arachidonyl
      glycerol is mediated through down-regulation of the nuclear factor of activated T
      cells.
AB  - 2-Arachidonyl-glycerol (2-Ara-Gl) recently was identified as a putative
      endogenous ligand for cannabinoid receptor types CB1 and CB2 by competitive
      binding. More recent immune function assays demonstrated that 2-Ara-Gl possessed
      immunomodulatory activity. Because several plant-derived cannabinoids inhibit
      interleukin-2 (IL-2) expression, 2-Ara-Gl was investigated for its ability to
      modulate this cytokine. The direct addition of 2-Ara-Gl to mouse splenocyte
      cultures suppressed phorbol-12-myristate-13-acetate plus ionomycin-induced IL-2
      secretion and steady state mRNA expression in a dose-dependent manner. 2-Ara-Gl
      also produced a marked inhibition of IL-2 promotor activity as determined by
      transient transfection of EL4.IL-2 cells with a pIL-2-CAT construct. 2-Ara-Gl at
      5, 10, 20, and 50 microM suppressed phorbol-12-myristate-13-acetate plus
      ionomycin-induced IL-2 promotor activity by 18%, 28%, 39%, and 54%, respectively.
      To further characterize the mechanism for the transcriptional regulation of IL-2
      by 2-Ara-Gl, the DNA-binding activity of transcription factors, nuclear factor of
      activated T cells (NF-AT), nuclear factor for immunoglobulin kappa chain in B
      cells (NF-kappa B/Rel), activator protein-1(AP-1), octamer, and cAMP-response
      element binding protein was evaluated by electrophoretic mobility shift assay in
      mouse splenocytes. In addition, a reporter gene expression system for p(NF-kappa
      B)3-CAT, p(NF-AT)3-CAT, and p(AP-1)3-CAT was used in transiently transfected
      EL4.IL-2 cells to determine the effect of 2-Ara-Gl on promoter activity for each
      of the specific transcription factors. 2-Ara-Gl reduced both the NF-AT-binding
      and promoter activity in a dose-dependent manner and, to a lesser degree, NF
      kappa B/Rel-binding and promoter activity. No significant effect was observed on
      octamer- and cAMP-response element-binding activity. AP-1 DNA-binding activity
      was not inhibited by 2-Ara-Gl, but a modest inhibition of promoter activity was
      observed.

PMID- 9547359
TI  - N-Methyl-D-aspartate attenuates opioid receptor-mediated G protein activation and
      this process involves protein kinase C.
AB  - The effects of N-methyl-D-aspartate (NMDA) on opioid receptor-mediated G protein
      activation were explored in neuroblastoma X glioma hybrid (NG108-15) cells.
      Treatment of the cells with NMDA resulted in a remarkable attenuation of
      [35S]guanosine-5'-O-(3-thio)triphosphate binding stimulated by [D-Pen2,D-Pen5]
      enkephalin (DPDPE), a delta-opioid receptor agonist. The effects of NMDA were
      dose and time dependent with an IC50 value of 5 nM and could be blocked by NMDA
      receptor antagonists. After NMDA treatment, the DPDPE dose-response curve shifted
      to the right (EC50 value increased approximately 7-fold, from 6 to 40 nM), and
      the maximal response induced by DPDPE was reduced by approximately 60%. The
      effects of NMDA were reversible, and the DPDPE response could recover within 60
      min. The functional responses of delta-, mu-, and kappa-opioid receptors in
      primarily cultured neurons also were attenuated significantly by NMDA treatment.
      The inhibitory effects of NMDA on opioid receptor-mediated G protein activation
      could be blocked by coadministration of the protein kinase C (PKC) inhibitors or
      by elimination of the extracellular Ca2+. Correspondingly, NMDA treatment of
      NG108 cells significantly elevated cellular PKC activity and stimulated Gialpha2
      phosphorylation. Transient transfection into NG108-15 cells of the wild-type
      Gialpha2 and a mutated Gialpha2 (Ser144Ala) resulted in a 2-fold increase in
      DPDPE-stimulated G protein activation. The DPDPE responses were greatly inhibited
      by NMDA treatment in the wild-type Gialpha2-transfected cells but much less
      affected in the mutant Gialpha2-transfected cells. In summary, NMDA attenuates
      opioid receptor/G protein coupling, and this process requires activation of PKC.

PMID- 9547360
TI  - Protein kinase C activity is required for aryl hydrocarbon receptor pathway
      mediated signal transduction.
AB  - The role of protein kinase C (PKC) in the human aryl hydrocarbon receptor (hAhR)
      signal transduction pathway was examined in cell lines stably transfected with
      pGUDLUC6.1, in which luc+ is solely controlled by four dioxin-responsive elements
      (DREs). These cell lines, P5A11 and HG40/6, were derived from HeLa and HepG2
      cells respectively. Simultaneous treatment of these cells with 2,3,7,8, 
      tetrachlorodibenzo-p-dioxin (TCDD) and phorbol-12-myristate-13-acetate (PMA)
      enhanced trans-activation of the reporter construct several-fold relative to
      cells treated with TCDD alone. PKC inhibitors block the PMA effect and hAhR
      mediated signal transduction, demonstrating these processes require PKC activity.
      Examination of other independently generated, HeLa-derived cell lines stably
      transfected with pGUDLUC6.1 demonstrates the PMA effect in P5A11 cells is not a
      clonal artifact. Transient transfections indicate the PMA effect is not due to a
      luciferase message/gene product stabilization mechanism or stimulation of the
      basal transcription machinery. Examination of cytosolic preparations demonstrates
      PKC stimulation or inhibition does not alter hAhR and hAhR nuclear translocator
      protein levels or TCDD-induced down-regulation of hAhR levels. Similarly,
      examination of nuclear extracts indicated PKC stimulation or inhibition does not
      alter nuclear AhR levels or hAhR/hAhR nuclear translocator protein heterodimer
      DRE-binding activity as assessed by electrophoretic mobility shift assay. These
      results demonstrate a PKC-mediated event is required for the hAhR to form a
      functional transcriptional complex that leads to trans-activation and that the
      DRE is the minimal DNA element required for PMA to enhance AhR-mediated trans
      activation.

PMID- 9547361
TI  - Nuclear localization of overexpressed glyceraldehyde-3-phosphate dehydrogenase in
      cultured cerebellar neurons undergoing apoptosis.
AB  - We recently reported that overexpression of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH; EC 1.2.1.12) is directly involved in cytosine
      arabinonucleoside (ara-C)- and low K+-induced neuronal death of cultured
      cerebellar granule cells. The former is entirely due to apoptosis, whereas the
      latter involves both apoptosis and necrosis. We examined the subcellular
      distribution of the overexpressed GAPDH occurring during apoptosis by using both
      subcellular fractionation and immunocytochemistry with a monoclonal antibody
      directed against this overexpressed protein. When immature cerebellar neurons
      were exposed to ara-C, an overexpression of GAPDH was observed, primarily in the
      nuclear fraction. In contrast, low K+ exposure of mature cerebellar neurons
      induced the overexpression of GAPDH not only in the nuclear fraction but also in
      the mitochondrial fraction. In both paradigms, no significant change of GAPDH
      levels occurred in the microsomal and cytosolic fractions. Moreover, pretreatment
      with GAPDH antisense oligonucleotide or classic apoptotic inhibitors clearly
      suppressed the accumulation of GAPDH protein in these subcellular loci. This
      discrete nuclear localization of GAPDH during apoptosis was supported further by
      immunoelectron microscopy. Quantitative assessment of GAPDH immunogold labeling
      revealed that a approximately 5-fold increase in the intensity of gold particles
      was observed within the nucleus of apoptotic cells. Thus, the current results
      raise the possibility that neuronal apoptosis may be triggered by GAPDH
      accumulation in the nucleus, resulting in perturbation of nuclear function and
      ultimate cell death.

PMID- 9547362
TI  - Human histamine N-methyltransferase pharmacogenetics: common genetic
      polymorphisms that alter activity.
AB  - Histamine N-methyltransferase (HNMT) catalyzes a major pathway in histamine
      metabolism. Levels of HNMT activity in humans are regulated by inheritance. We
      set out to study the molecular basis for this genetic regulation. Northern blot
      analysis showed that HNMT is highly expressed in the kidney, so we determined
      levels of enzyme activity and thermal stability in 127 human renal biopsy
      samples. DNA was isolated from 12 kidney samples with widely different HNMT
      phenotypes, and exons of the HNMT gene were amplified with the polymerase chain
      reaction. In these 12 samples, we observed a C314T transition that resulted in a
      Thr105Ile change in encoded amino acid, as well as an A939G transition within the
      3'-untranslated region. All remaining renal biopsy samples then were genotyped
      for these two variant sequences. Frequencies of the alleles encoding Thr105 and
      Ile105 in the 114 samples studied were 0.90 and 0.10, respectively, whereas
      frequencies for the nucleotide A939 and G alleles were 0.79 and 0.21,
      respectively. Kidney samples with the allele encoding Ile105 had significantly
      lower levels of HNMT activity and thermal stability than did those with the
      allele that encoded Thr105. These observations were confirmed by transient
      expression in COS-1 cells of constructs that contained all four alleles for these
      two polymorphisms. COS-1 cells transfected with the Ile105 allele had
      significantly lower HNMT activity and immunoreactive HNMT protein than did those
      transfected with the Thr105 allele. These observations will make it possible to
      test the hypothesis that genetic polymorphisms for HNMT may play a role in the
      pathophysiology of human disease.

PMID- 9547363
TI  - Acceleration of oxime-induced reactivation of organophosphate-inhibited fetal
      bovine serum acetylcholinesterase by monoquaternary and bisquaternary ligands.
AB  - Reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) by
      oximes is the primary reason for their effectiveness in the treatment of OP
      poisoning. Reactivation is reported to accelerate by quaternary ligands such as
      decamethonium, which is devoid of nucleophilicity. The mechanism of this
      enhancement is not known. To better understand the acceleration phenomenon, we
      examined ligand modulations of oxime-induced reactivation of methylphosphonylated
      AChE using 7-(methylethoxyphosphinyloxy)-1-methylquinolinium iodide and fetal
      bovine serum AChE. Edrophonium, decamethonium, and propidium, three quaternary
      AChE ligands of different types, were tested as potential accelerators.
      Experiments were carried out with both soluble enzyme preparation and AChE
      conjugated to polyurethane. Kinetic measurements with oximes 2
      [hydroxyiminomethyl]-1-methylpyridinium chloride, 1,1'-trimethylene bis-(4
      hydroxyimino methyl)-pyridinium dibromide, and 1, 1'-[oxybis-methylene)bis[4
      (hydroxyimino)methyl]pyridiniu um dichloride showed that in the presence of 50
      microM edrophonium, the reactivation rate constants increased 3.3-12.0-fold; 200
      microM decamethonium produced a 1.6-3.0-fold enhancement of reactivation rate
      constants by the same oximes. Reactivation of the inhibited enzyme by 1-(2
      hydroxyiminomethyl-1-pyridinium)-1-(4-carboxy-aminopyridinium )-d imethyl ether
      hydrochloride, 1-(2-hydroxyiminomethyl-1-pyridinium)-1-(3-carboxy-aminopyridinium
      )-d imethyl ether hydrochloride, and 1-[[[4
      (aminocarbonyl)pyridino]methoxy]methyl]-2, 4, -bis(hydroxyimino)methyl pyridinium
      dichloride was not affected by either ligand. Propidium slowed the reactivation
      of 7-(methylethoxyphosphinyloxy)-1- methylquinolinium iodide-inhibited AChE by
      all oximes. Results suggest that the accelerator site may reside inside the
      catalytic gorge rather than at its entrance and acceleration may be due to the
      prevention of reinhibition of the regenerated enzyme by the putative product, the
      phosphonylated oxime. In addition to the nucleophilic property of the oximate
      anion, some of the reactivators may carry an accelerating determinant, as
      characterized with respect to edrophonium and decamethonium. Results offer
      possible explanations for the superiority of 1-(2-hydroxyiminomethyl-1
      pyridinium)-1-(4-carboxy-aminopyridinium )-d imethyl ether hydrochloride over
      other oximes in the reactivation of specific AChE-OP conjugates.

PMID- 9547364
TI  - ATP derivatives are antagonists of the P2Y1 receptor: similarities to the
      platelet ADP receptor.
AB  - Pharmacological properties of the human P2Y1 receptor transfected in Jurkat cells
      and of the endogenous receptor in rat brain capillary endothelial cells were
      analyzed under conditions in which the purity of adenine triphosphate nucleotides
      was controlled by creatine phosphate/creatine phosphokinase (CP/CPK). ATP, a
      partial agonist of the receptor, was inactive in the presence of CP/CPK. Results
      further indicated that ATP was a competitive antagonist of ADP actions. Ki values
      were 23.0 +/- 1.5 microM in endothelial cells and 14.3 +/- 0.3 microM in Jurkat
      cells. Solutions prepared from commercially available 2-methylthio-ATP (2-MeSATP)
      or 2-chloro-ATP (2-ClATP) contained approximately 10% of ADP derivatives. ADP
      derivatives were removed from the solution by treatment with CP/CPK. Purified 2
      MeSATP and 2-ClATP antagonized platelet aggregation induced by ADP. They did not
      activate P2Y1 receptors but prevented ADP actions in a competitive manner. Ki
      values for 2-MeSATP were 36. 5 microM in endothelial cells and 5.7 +/- 0.4 microM
      in Jurkat cells, and Ki values for 2-ClATP were 27.5 microM in endothelial cells
      and 2.3 +/- 0.3 microM in Jurkat cells. EDTA potentiated actions of ADP and ATP
      on endothelial cells by 2.4- and 3.6-fold, respectively. In conclusion, the rat
      and human P2Y1 receptors are ADP-specific receptors that recognize ADP and 2
      methylthio-ADP, whereas ATP, 2-MeSATP, and 2-ClATP are competitive antagonists.
      The results further point to the close pharmacological similarity of the P2Y1
      receptor and the platelet ADP receptor.

PMID- 9547365
TI  - Plasma membrane depolarization and disturbed Na+ homeostasis induced by the
      protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon in isolated nerve
      terminals.
AB  - The effect of the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon
      (FCCP) was studied on the intracellular [Na+], pH, and plasma membrane potential
      in isolated nerve terminals. FCCP induced a rise of [Na+]i at, and even below,
      the concentrations (0.025-1 microM) in which it is usually used in intact cells
      to eliminate Ca2+ uptake by mitochondria. The FCCP-induced increase of [Na+]i
      correlates with a fall in both the ATP level and the ATP/ADP ratio. In addition,
      a sudden rise of the intracellular proton concentration ([H+]i) from 83 +/- 0.4
      to 124 +/- 0.7 nM was observed on the addition of FCCP (1 microM). Parallel with
      the rise in [H+]i, an abrupt depolarization was detected, followed by a slower
      decrease in the plasma membrane potential. Both the extent of the pHi change and
      the fast depolarization of the plasma membrane were proportional to the proton
      electrochemical gradient across the plasma membrane; when this gradient was
      increased, greater depolarization was detected. The slower decrease of the
      membrane potential after the fast initial depolarization was abolished when the
      medium contained no Na+. It is concluded that FCCP (1) gives rise to a
      depolarization by setting the plasma membrane potential close to the proton
      equilibrium potential and (2) enhances the intracellular [Na+] as a consequence
      of an insufficient ATP level and ATP/ADP ratio to fuel the Na+,K+/ATPase. Because
      both disturbed Na+ homeostasis and plasma membrane depolarization could
      profoundly interfere with Ca2+ homeostasis in the presence of protonophores,
      consideration given to these alterations may help to clarify the cellular Ca2+
      sequestration processes.

PMID- 9547366
TI  - Reverse Na+/Ca2+ exchange contributes to glutamate-induced intracellular Ca2+
      concentration increases in cultured rat forebrain neurons.
AB  - Activation of ionotropic glutamate receptors causes increases in intracellular
      Ca2+ concentration ([Ca2+]i) and intracellular Na+ concentration in neurons. It
      has been suggested that reversal of the plasma membrane Na+/Ca2+ exchanger (NCE)
      may account in part for the rise in [Ca2+]i. Recently, KB-R7943 (2-[2-[4-(4
      nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) was reported to
      selectively inhibit the reverse mode of the NCE in non-neuronal cells. We
      investigated the effects of KB-R7943 on glutamate-stimulated increases in
      [Ca2+]i. In cultured rat forebrain neurons loaded with indo-1 acetoxymethyl
      ester, KB-R7943 inhibited the reverse mode of NCE (IC50 = 0.7 microM). When
      tested against kainate- (100 microM), N-methyl-D-aspartate- (30 microM),
      glutamate- (3 microM), or KCl- (50 mM) induced [Ca2+]i transients (15 sec, in the
      presence of Na+ and Ca2+), KB-R7943 inhibited these transients with IC50 values
      of 6. 6, 8.2, 5.2, and 2.9 microM, respectively. [Ca2+]i increases caused by a
      higher concentration of glutamate (100 microM) also were inhibited by KB-R7943
      (10 microM). However, KB-R7943 had no effect on peak [Ca2+]i changes caused by
      prolonged application of glutamate and did not inhibit glutamate-induced neuronal
      injury. KB-R7943 did not inhibit N-methyl-D-aspartate- or kainate-induced whole
      cell currents, nor did it substantially inhibit voltage-sensitive Ca2+ currents,
      excluding a direct inhibition of these ion channels. These results suggest that
      reverse NCE contributes to the immediate rise in [Ca2+]i resulting from glutamate
      receptor activation. However, reverse NCE becomes less important as the stimulus
      time is increased, and Ca2+ entry by this route is not critical for the
      expression of excitotoxic injury.

PMID- 9547367
TI  - Identification and characterization of two cysteinyl-leukotriene high affinity
      binding sites with receptor characteristics in human lung parenchyma.
AB  - We report the characterization of two distinct binding sites with receptor
      characteristics for leukotriene (LT)D4 and LTC4 in membranes from human lung
      parenchyma. The use of S-decyl-glutathione allowed us to characterize a
      previously unidentified high affinity binding site for LTC4. Computerized
      analysis of binding data revealed that each leukotriene interacts with two
      distinct classes of binding sites (Kd = 0.015 and 105 nM for LTC4 and 0.023 and
      230 nM for LTD4) and that despite cross-reactivity, the two high affinity sites
      are different entities. LTD4 binding sites displayed features of G protein
      coupled receptors, whereas LTC4 binding sites did not show any significant
      modulation by guanosine-5'-(beta, gamma-imido)triphosphate or stimulation of
      GTPase activity. The antagonists ICI 198,615 and SKF 104353 were unselective for
      the high and low affinity states of LTD4 receptor, whereas only SKF 104353 was
      able to recognize the two [3H]LTC4 binding sites although with different
      affinities. These data indicate that in human lung parenchyma, LTD4 and LTC4
      recognize two different binding sites; these binding sites are different
      entities; and for LTD4, the two binding sites represent the interconvertible
      affinity states of a G protein-coupled receptor, whereas for LTC4, the high
      affinity site is likely to be a specific LTC4 receptor.

PMID- 9547368
TI  - The relationship between agonist intrinsic activity and the rate of endocytosis
      of muscarinic receptors in a human neuroblastoma cell line.
AB  - The molecular mechanisms underlying the internalization of G protein-coupled
      receptors are still poorly understood. Normally agonists but not antagonists
      cause internalization (defined here as a reduction in the number of receptors at
      the cell surface), suggesting a functional relationship between agonist activity
      and internalization. In this study we investigated the effects of eight
      muscarinic ligands on the rate constants for endocytosis and recycling of m3
      muscarinic acetylcholine receptors in human SH-SY5Y neuroblastoma cells. We found
      that there was a linear correlation between the intrinsic activity of the ligand
      and its ability to increase the rate constant for endocytosis, suggesting that
      the same active conformation of the receptor is responsible for stimulating both
      second messenger generation and receptor endocytosis. In contrast, the rate
      constant for recycling did not depend on which agonist had triggered receptor
      endocytosis, suggesting that recycling is a purely constitutive process. Because
      receptor internalization depends on the rate constants for both endocytosis and
      recycling, the relationship between internalization and intrinsic activity is
      nonlinear. In particular, mathematical modeling of receptor trafficking revealed
      that under certain conditions very small (3% or less) increases in the rate
      constant for endocytosis are sufficient to cause substantial receptor
      internalization. An important implication of this analysis is that extremely weak
      partial agonists (which may in practice be indistinguishable from antagonists)
      may produce significant receptor internalization.

PMID- 9547369
TI  - The agonism and synergistic potentiation of weak partial agonists by
      triethylamine in alpha 1-adrenergic receptor activation: evidence for a salt
      bridge as the initiating process.
AB  - Alpha 1-adrenergic receptor (AR) activation is thought to be initiated by
      disruption of a constraining interhelical salt bridge (). Disruption of this salt
      bridge is achieved through a competition for the aspartic acid residue in
      transmembrane domain three by the protonated amine of the endogenous ligand
      norepinephrine and a lysine residue in transmembrane domain seven. To further
      test this hypothesis, we investigated the possibility that a simple amine could
      mimic an important functional group of the endogenous ligand and break this alpha
      1-AR ionic constraint leading to agonism. Triethylamine (TEA) was able to
      generate concentration-dependent increases of soluble inositol phosphates in COS
      1 cells transiently transfected with the hamster alpha 1b-AR and in Rat-1
      fibroblasts stably transfected with the human alpha 1a-AR subtype. TEA was also
      able to synergistically potentiate the second messenger production by weak
      partial alpha 1-AR agonists and this effect was fully inhibited by the alpha 1-AR
      antagonist prazosin. However, this synergistic potentiation was not observed for
      full alpha 1-AR agonists. Instead, TEA caused a parallel rightward shift of the
      dose-response curve, consistent with the properties of competitive antagonism.
      TEA specifically bound to a single population of alpha 1-ARs with a Ki of 28.7 +/
      4.7 mM. In addition, the site of binding by TEA to the alpha 1-AR is at the
      conserved aspartic acid residue in transmembrane domain three, which is part of
      the constraining salt bridge. These results indicate a direct interaction of TEA
      in the receptor agonist binding pocket that leads to a disruption of the
      constraining salt bridge, thereby initiating alpha 1-AR activation.

PMID- 9547370
TI  - Creating a functional opioid alkaloid binding site in the orphanin FQ receptor
      through site-directed mutagenesis.
AB  - Although much has been learned about the mechanisms of ligand selectivity between
      different opioid receptor subtypes, little is known about the common opioid
      binding pocket shared by all opioid receptors. The recently discovered orphanin
      system offers a good opportunity to study the mechanisms involved in the binding
      of opioid versus nonopioid ligands. In the current study, we adopt a "gain of
      function" approach aimed at shifting the binding profile of the orphanin FQ
      receptor toward that of the opioid receptors. After two rounds of mutagenesis,
      several orphanin FQ receptor mutants can be labeled with the opiate alkaloid
      [3H]naltrindole and show greatly increased affinities toward the opiate
      antagonists naltrexone, nor-binaltrophine HCl, and (-)-bremazocine. These
      orphanin FQ receptor mutants also display stereospecificity similar to that of
      opioid receptors. Furthermore, the orphanin FQ receptor mutant that has the best
      affinities toward the opioid alkaloids shows, in the presence of GTP and high
      salt concentration, an affinity-shift profile similar to that of the delta
      receptor. Most strikingly, the same mutant exhibits naltrindole-sensitive
      etorphine-stimulated [35S]guanosine-5'-O-(3-thio)triphosphate binding, whereas
      the effect of etorphine on GTP binding cannot be inhibited by naltrindole in the
      wild-type receptor. Our results indicate that 1) several residues in the orphanin
      FQ receptor are critical to its selectivity against the opiate alkaloids,
      particularly antagonists; and 2) mutating these residues to those of the opioid
      receptor at the corresponding position preserves the agonist/antagonist nature of
      opiate alkaloids as they interact with the mutant receptor. It is reasonable to
      hypothesize that the corresponding residues in the opioid receptors may form a
      functional common binding pocket for opiate alkaloids. These findings may be
      helpful to medicinal chemists in designing ligands for the orphanin FQ receptor
      based on the structure of the opiate alkaloids.

PMID- 9547371
TI  - The G protein-coupling profile of metabotropic glutamate receptors, as determined
      with exogenous G proteins, is independent of their ligand recognition domain.
AB  - Metabotropic glutamate (mGlu), Ca2+-sensing, gamma-aminobutyric acidB, and a
      large number of pheromone receptors constitute a peculiar family of G protein
      coupled receptors. They possess a large extracellular domain that has been
      proposed to constitute their ligand binding domain. The aim of the current study
      was to examine whether this large ligand binding domain had any influence on the
      G protein-coupling selectivity of the receptor, and vice versa. We chose mGlu
      receptors, which are classified into three groups according to their sequence
      homology and pharmacology, as representatives of this receptor family. To define
      a G protein-coupling profile for these receptors, we used a set of exogenous
      phospholipase C-activating G proteins in the same way that synthetic ligands are
      used to define agonist and antagonist pharmacological profiles. This set includes
      Galpha15, Galpha16, Galphaq, and chimeric Galphaq proteins with the last few
      amino acids of either Galphai2 (Galphaqi), Galphao (Galphaqo), or Galphaz
      (Galphaqz). Cotransfection of mGlu receptors with these G proteins and
      examination of their coupling to phospholipase C revealed that group I, II, and
      III receptors have distinct G protein-coupling profiles. By swapping the
      extracellular domains of the most distantly related mGlu receptors (the rat group
      I mGlu1a and the Drosophila melanogaster group II DmGluA receptors), we show that
      the extracellular domain determines the agonist pharmacological profile and that
      this domain does not modify the G protein-coupling profile determined by the
      seven-transmembrane-domain region of mGlu receptors.

PMID- 9547372
TI  - Residues at the subunit interfaces of the nicotinic acetylcholine receptor that
      contribute to alpha-conotoxin M1 binding.
AB  - The two binding sites in the pentameric nicotinic acetylcholine receptor of
      subunit composition alpha2 beta gamma delta are formed by nonequivalent alpha
      gamma and alpha-delta subunit interfaces, which produce site selectivity in the
      binding of agonists and antagonists. We show by sedimentation analysis that 125I
      alpha-conotoxin M1 binds with high affinity to the alpha-delta subunit dimers,
      but not to alpha-gamma dimers, nor to alpha, gamma, and delta monomers, a finding
      consistent with alpha-conotoxin M1 selectivity for the alpha delta interface in
      the intact receptor measured by competition against alpha-bungarotoxin binding.
      We also extend previous identification of alpha-conotoxin M1 determinants in the
      gamma and delta subunits to the alpha subunit interface by mutagenesis of
      conserved residues in the alpha subunit. Most mutations of the alpha subunit
      affect affinity similarly at the two sites, but Tyr93Phe, Val188Lys, Tyr190Thr,
      Tyr198Thr, and Asp152Asn affect affinity in a site-selective manner. Mutant cycle
      analysis reveals only weak or no interactions between mutant alpha and non-alpha
      subunits, indicating that side chains of the alpha subunit do not interact with
      those of the gamma or delta subunits in stabilizing alpha-conotoxin M1. The
      overall findings suggest different binding configurations of alpha-conotoxin M1
      at the alpha-delta and alpha-gamma binding interfaces.

PMID- 9547373
TI  - Molecular actions of a Mn(III)Porphyrin superoxide dismutase mimetic and
      peroxynitrite scavenger: reaction with nitric oxide and direct inhibition of NO
      synthase and soluble guanylyl cyclase.
AB  - Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), described as a superoxide
      dismutase mimetic and peroxynitrite scavenger, has been used previously to
      investigate the cytotoxic potential of superoxide and peroxynitrite in several
      pathological models. Here we report on the interference of MnTMPyP with NO/cGMP
      signaling using cultured endothelial cells as well as purified soluble guanylyl
      cyclase (sGC) either activated by the NO donor 2,2-diethyl-1-nitroso-oxyhydrazine
      sodium salt (DEA/NO) or reconstituted with nitric oxide synthase (NOS). MnTMPyP
      inhibited endothelial cGMP accumulation induced by A23187 (0.3 microM) with an
      IC50 of 75.0 +/- 10.4 microM but had no significant effect on the potency of the
      Ca2+ ionophore. Purified NOS was inhibited by MnTMPyP (IC50 = 5.5 +/- 0.8 microM)
      because of an interference of the Mn-porphyrin with the reductase domain of the
      enzyme. The most pronounced actions of MnTMPyP were direct inhibition of sGC and
      scavenging of NO. Purified sGC stimulated with either Ca2+/calmodulin-activated
      NOS (in the presence of GSH) or DEA/NO (in the absence of GSH) was inhibited with
      IC50 values of 0.8 +/- 0.09 microM and 0.6 +/- 0.2 microM, respectively. In the
      presence of GSH, MnTMPyP was reduced to the Mn(II) complex, resulting in
      efficient scavenging of NO under these conditions. Our data demonstrate that
      MnTMPyP (i) interferes with the reductase domain of NOS, (ii) scavenges NO in the
      presence of GSH, and (iii) is a potent direct inhibitor of sGC. These results
      cast doubt on the usefulness of MnTMPyP and related Mn-porphyrin complexes as
      probes to study the involvement of peroxynitrite/superoxide in biological
      systems.

PMID- 9547374
TI  - Direct and indirect regulation of a single ion channel.

PMID- 9547375
TI  - The revival of the role of the mitochondrion in regulation of transmitter
      release.

PMID- 9547376
TI  - Rhythmicity, synchronization and binding in human and primate motor systems.
AB  - This review focuses on recent advances in our understanding of temporal pattern
      coding in the motor systems of animals and man. Examples of millisecond time
      scale rhythmic synchronization in the visual system are considered. Results of
      experiments that demonstrate similar phenomena in the motor system are discussed.
      Finally problems concerning the nature of the correlation between
      neurophysiological signals and the relationship of correlation to motor behaviour
      are explored.

PMID- 9547377
TI  - Facilitation of rabbit alpha1B calcium channels: involvement of endogenous
      Gbetagamma subunits.
AB  - 1. The alpha1B (N-type) calcium channel shows strong G protein modulation in the
      presence of G protein activators or Gbetagamma subunits. Using transient
      expression in COS-7 cells of alpha1B together with the accessory subunits alpha2
      delta and beta2a, we have examined the role of endogenous Gbetagamma subunits in
      the tonic modulation of alpha1B, and compared this with modulation by exogenously
      expressed Gbetagamma subunits. 2. Prepulse facilitation of control alpha1B/alpha2
      delta/beta2a currents was always observed. This suggests the existence of tonic
      modulation of alpha1B subunits. To determine whether endogenous Gbetagamma is
      involved in the facilitation observed in control conditions, the betaARK1
      Gbetagamma-binding domain (amino acids 495-689) was overexpressed, in order to
      bind free Gbetagamma subunits. The extent of control prepulse-induced
      facilitation was significantly reduced, both in terms of current amplitude and
      the rate of current activation. In agreement with this, GDPbetaS also reduced the
      control facilitation. 3. Co-expression of the Gbeta1gamma2 subunit, together with
      the alpha1B/alpha2-delta/beta2a calcium channel combination, resulted in a marked
      degree of depolarizing prepulse-reversible inhibition of the whole-cell ICa or
      IBa. Both slowing of current activation and inhibition of the maximum current
      amplitude were observed, accompanied by a depolarizing shift in the mid-point of
      the voltage dependence of activation. Activation of endogenous Gbetagamma
      subunits by dialysis with GTPgammaS produced a smaller degree of prepulse
      reversible inhibition. 4. The rate of reinhibition of alpha1B currents by
      activated G protein, following a depolarizing prepulse, was much faster with
      Gbeta1gamma2 than for the decay of facilitation in control cells. Furthermore,
      betaARK1 (495-689) co-expression markedly slowed the control rate of
      reinhibition, suggesting that the kinetics of reinhibition depend on the
      concentration of free endogenous or exogenously expressed Gbetagamma in the
      cells. In contrast, the rate of loss of inhibition during a depolarizing prepulse
      did not vary significantly between the different conditions examined. 5. These
      findings indicate that, in this system, the voltage-dependent facilitation of
      alpha1B that is observed under control conditions occurs as a result of
      endogenous free Gbetagamma binding to alpha1B.

PMID- 9547378
TI  - Voltage change-induced gating transitions of the rabbit skeletal muscle Ca2+
      release channel.
AB  - 1. We used the planar lipid bilayer method to study single ryanodine receptor
      Ca2+ release channels (RyRCs) from fast skeletal muscle of the rabbit. We found
      that changes in membrane voltage directly induced gating transitions of the RyRC:
      (i) in the steady state, even at activating Ca2+ concentrations (20 microM), at a
      constant membrane potential the channels resided in a low open probability (Po)
      state (inactivated-, I-mode), and (ii) upon abrupt changes of voltage, the
      apparent inactivation of the RyRCs was relieved, resulting in a rapid and
      transient increase in Po. 2. The magnitude of the Po increase was a function of
      both the duration and the amplitude of the applied prepulse, but was independent
      of the channel activity during the prepulse. 3. The voltage-induced Po increase
      probably involved major conformational changes of the channel, as it resulted in
      substantial alterations in the gating pattern of the channels: the voltage change
      induced increase in Po was accompanied by the rapid appearance of two types of
      channel activity (high (H) and low (L) open probability modes). 4. The response
      of the RyRC to voltage changes raises the interesting possibility that the
      activation of RyRC in situ might involve electrical events, i.e. a possible
      dipole-dipole coupling between the release channel and the voltage sensor.

PMID- 9547379
TI  - Calcium-dependent inactivation of high-threshold calcium currents in human
      dentate gyrus granule cells.
AB  - 1. Dentate gyrus granule cells acutely dissociated from hippocampal slices
      obtained from chronic temporal lobe epilepsy (TLE) patients displayed a high
      voltage activated (HVA) Ca2+ conductance with a pronounced Ca2+-dependent
      inactivation. 2. Inactivation time constants and peak HVA Ca2+ current (ICa)
      amplitudes did not differ between perforated patch and whole-cell recordings
      without added exogenous Ca2+ buffers, indicating that the Ca2+-dependent
      characteristics of ICa inactivation were well preserved in whole-cell recordings.
      3. Inactivation time constants correlated with whole-cell ICa, and were increased
      when Ca2+ was replaced with Ba2+ in the external solution or 5 mM BAPTA was added
      to the pipette solution. 4. In recordings without added exogenous Ca2+ buffers,
      the time course of ICa inactivation was comparable between human TLE and kindled
      rat granule cells. Conversely, the time course of ICa in human TLE granule cells
      loaded with 5 mM intracellular BAPTA resembled that observed in buffer-free
      recordings from control rat neurones. 5. The loss of a putative intraneuronal
      Ca2+ buffer, the Ca2+-binding protein calbindin (CB), from human granule cells
      during TLE may result in the pronounced Ca2+-dependent ICa inactivation. This
      process could serve a neuroprotective role by significantly decreasing Ca2+ entry
      during prolonged trains of action potentials known to occur during seizures.

PMID- 9547380
TI  - Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal
      grey neurons.
AB  - 1. The actions of the neuropeptide nociceptin on the calcium channel currents
      (IBa) of acutely dissociated rat periaqueductal grey (PAG) neurons were examined
      using whole-cell patch clamp techniques. These effects were compared with those
      of opioid receptor agonists and the GABAB receptor agonist baclofen. 2. Neurons
      from young adult rats (23 to 56 days old) expressed predominantly omega-conotoxin
      GVIA (N-type)- and omega-agatoxin IVA (P/Q-type)-sensitive IBa, together with
      smaller amounts of nimodipine-sensitive current and current resistant to all
      three blockers. There was proportionately more N-type IBa in neurons from female
      rats and proportionately more resistant current in neurons from male rats. 3.
      Nociceptin (EC50, 5 nM) and baclofen (EC50, 0.8 microM) inhibited IBa in all PAG
      neurons, while the opioid agonist methionine enkephalin (met-enkephalin; 300 nM
      10 microM) inhibited IBa in 40 % of neurons. The effects of met-enkephalin were
      reversed by the mu-opioid antagonist CTAP, and mimicked by the mu-opioid agonist
      DAMGO (300 nM-3 microM). The delta-opioid agonists DPDPE and deltorphin II, and
      the kappa-opioid agonist U69593, did not affect IBa in any neuron. The actions of
      nociceptin were not mimicked or blocked by the opioid antagonist naloxone or the
      nociceptin analogue [desPhe1]-nociceptin. 4. The effects of nociceptin and
      baclofen on IBa were blocked by pretreatment of the neurons with pertussis toxin
      (500 ng ml-1, 8 h). 5. Nociceptin predominantly inhibited the N-type (EC50, 2 nM;
      maximum inhibition, 50 %) and P/Q-type (EC50, 7 nM; maximum inhibition, 33 %) IBa
      while having little effect on the L-type and R-type IBa. 6. These results are
      consistent with the previously described actions of nociceptin, baclofen and
      micro-opioids in PAG slices, whereby they couple to increases in an inwardly
      rectifying K+ conductance. These agonists thus have the potential to modulate the
      function of PAG neurons via a number of different cellular effectors.

PMID- 9547381
TI  - Evidence that mitochondria buffer physiological Ca2+ loads in lizard motor nerve
      terminals.
AB  - 1. Changes in cytosolic and mitochondrial [Ca2+] produced by brief trains of
      action potentials were measured in motor nerve terminals using a rapidly scanning
      confocal microscope. Cytosolic [Ca2+] was measured using ionophoretically
      injected Oregon Green BAPTA 5N (OG-5N). Mitochondrial [Ca2+] was measured using
      rhod-2, bath loaded as dihydrorhod-2. 2. In response to 100-250 stimuli at 25-100
      Hz the average cytosolic [Ca2+] showed an initial rapid increase followed by a
      much slower rate of increase. Mitochondrial [Ca2+] showed no detectable increase
      during the first fifteen to twenty stimuli, but after this initial delay also
      showed an initially rapid rise followed by a slower rate of increase. The onset
      of the increase in mitochondrial [Ca2+] coincided with the slowing of the rate of
      rise of cytosolic [Ca2+]. The peak levels of cytosolic and mitochondrial [Ca2+]
      both increased with increasing frequencies of stimulation. 3. When stimulation
      terminated, the initial rate of decay of cytosolic [Ca2+] was much more rapid
      than that of mitochondrial [Ca2+]. 4. After addition of carbonyl cyanide m
      chlorophenyl hydrazone (CCCP, 1-2 microM) to dissipate the proton electrochemical
      gradient across the mitochondrial membrane, cytosolic [Ca2+] rose rapidly
      throughout the stimulus train, reaching levels much higher than normal. CCCP
      inhibited the increase in mitochondrial [Ca2+]. 5. These results suggest that
      mitochondrial uptake of Ca2+ contributes importantly to buffering presynaptic
      cytosolic [Ca2+] during normal neuromuscular transmission.

PMID- 9547382
TI  - A continuum of InsP3-mediated elementary Ca2+ signalling events in Xenopus
      oocytes.
AB  - 1. The elementary release events underlying inositol 1,4, 5-trisphosphate (InsP3)
      mediated calcium signalling were investigated in Xenopus oocytes by means of high
      resolution confocal linescan imaging together with flash photolysis of caged
      InsP3. 2. Weak photolysis flashes evoked localized, transient calcium signals
      that arose at specific sites following random latencies of up to several seconds.
      The duration, spatial spread and amplitude of these elementary events varied
      widely. Event durations (at half-maximal amplitude) were distributed
      exponentially between about 100 and 600 ms. Fluorescence magnitudes (F/F0 of
      Oregon Green 488 BAPTA-1) showed a skewed distribution with a peak at about 1.5
      and a tail extending as high as 3.5. 3. Individual release sites exhibited both
      small events (blips) and large events (puffs). The spatiotemporal distribution of
      calcium signals during puffs was consistent with calcium diffusion from a point
      source (< a few hundred nanometres), rather than with propagation of a
      microscopic calcium wave. 4. Estimates of the calcium flux associated with
      individual events were made by integrating fluorescence profiles along the scan
      line in three dimensions to derive the 'signal mass' at each time point. The
      smallest resolved events corresponded to liberation of < 2 x 10-20 mol Ca2+, and
      large events to about 2 x 10-18 mol Ca2+. The rise of signal mass was more
      prolonged than that of the fluorescence intensity, suggesting that calcium
      liberation persists even while the fluorescence begins to decline. Rates of rise
      of signal mass corresponded to Ca2+ currents of 0.4-2.5 pA. 5. Measurements of
      signal mass from different events showed a continuous, exponential distribution,
      arising through variability in magnitude and duration of calcium flux. 6. We
      conclude that localized calcium transients in the oocyte represent a continuum of
      events involving widely varying amounts of calcium liberation, rather than
      falling into separate populations of 'fundamental' and 'elementary' events (blips
      and puffs) involving, respectively, single and multiple InsP3 receptor channels.
      This variability probably arises through stochastic variation in both the number
      of channels recruited and the duration of channel opening.

PMID- 9547384
TI  - Activation of Ca2+-activated K+ channels by an increase in intracellular Ca2+
      induced by depolarization of mouse skeletal muscle fibres.
AB  - 1. Ionic currents were simultaneously recorded at macroscopic and unitary level
      using the whole-cell and cell-attached patch-clamp procedures together on the
      same portion of isolated mouse skeletal muscle fibres. 2. In the presence of
      Tyrode solution in the patch pipette and Tyrode-TTX solution in the bath,
      macroscopic and unitary currents through delayed rectifier K+ channels were
      simultaneously recorded in response to depolarizing pulses of 1 s duration. 3. In
      five fibres, successive long-lasting incremental depolarizing levels induced, at 
      40 mV or -30 mV, the opening of a high conductance channel carrying an outward
      current superimposed on delayed rectifier K+ channel activity. Opening of this
      high conductance channel was not observed when the depolarization steps were
      applied in the patch pipette. 4. Using the same depolarizing protocol, activation
      of a high conductance channel was also observed in two fibres in the presence of
      a K+-rich solution in the pipette (145 mM K+) . 5. With either Tyrode or K+-rich
      solution in the pipette, unitary current amplitudes of the high conductance
      channel matched well with the values obtained for Ca2+-activated K+ (KCa)
      channels in inside-out patches under similar ionic conditions. 6. Indo-1
      fluorescence measurements showed that the stimulation protocol that led to KCa
      channel opening induced stepwise increases in intracellular [Ca2+] in the
      submicromolar range. 7. Our results provide evidence that activation of
      sarcolemmal KCa channels can be induced by a rise in intracellular [Ca2+]
      following voltage-activated sarcoplasmic reticulum Ca2+ release.

PMID- 9547383
TI  - Activation and co-ordination of InsP3-mediated elementary Ca2+ events during
      global Ca2+ signals in Xenopus oocytes.
AB  - 1. The activation of elementary calcium release events ('puffs') and their co
      ordination to generate calcium waves was studied in Xenopus oocytes by confocal
      linescan imaging together with photorelease of inositol 1,4,5-trisphosphate
      (InsP3) from a caged precursor. 2. Weak photolysis flashes evoked no responses or
      isolated calcium puffs, whereas flashes of increasing strength evoked more
      frequent puffs, often occurring in flurries as abortive waves, and then a near
      simultaneous calcium liberation originating at multiple sites. The numbers of
      sites activated increased initially as about the fourth power of photoreleased
      [InsP3]. 3. Following repeated, identical photolysis flashes, puffs arose after
      stochastically varying latencies of a few hundred milliseconds to several
      seconds. The cumulative number of events initially increased as about the third
      power of time. No rise in free [Ca2+] was detected preceding the puffs,
      suggesting that this co-operativity arises through binding of multiple InsP3
      molecules, rather than through calcium feedback. 4. The mean latency to onset of
      calcium liberation shortened as about the square of the flash strength, and the
      dispersion in latencies between events reduced correspondingly. 5. Weak stimuli
      often evoked coupled puffs involving adjacent sites, and stronger flashes evoked
      saltatory calcium waves, propagating with non-constant velocity. During waves,
      [Ca2+] rose slowly between puff sites, but more abruptly at active sites
      following an initial diffusive rise in calcium. 6. Initial rates of rise of local
      [Ca2+] at release sites were similar during puffs and release induced by much (>
      10-fold) greater [InsP3]. In contrast, macroscopic calcium measurements averaged
      over the scan line showed a graded dependence of rate of calcium liberation upon
      [InsP3], due to recruitment of additional sites and decreasing dispersion in
      activation latencies. 7. We conclude that the initiation of calcium liberation
      depends co-operatively upon [InsP3] whereas the subsequent regenerative increase
      in calcium flux depends upon local calcium feedback and is largely independent of
      [InsP3]. Wave propagation is consistent with the diffusive spread of calcium
      evoking regenerative liberation at heterogeneous discrete sites, the sensitivity
      of which is primed by InsP3.

PMID- 9547385
TI  - The role of intracellular Na+ and mitochondria in buffering of kainate-induced
      intracellular free Ca2+ changes in rat forebrain neurones.
AB  - 1. We have examined the mechanisms by which cultured central neurones from
      embryonic rat brain buffer intracellular Ca2+ loads following kainate receptor
      activation using fluorescent indicators of [Ca2+]i and [Na+]i. 2. Stimulation of
      cultured forebrain neurones with 100 microM kainate produced a rapid increase in
      [Ca2+]i that displayed a variable rate of recovery. Kainate also increased [Na+]i
      with a response that was slightly slower in onset and markedly slower in
      recovery. 3. The recovery of [Ca2+]i to baseline was not very sensitive to the
      [Na+]i. The magnitude of the increase in [Na+]i in response to kainate did not
      correlate well with the [Ca2+]i recovery time, and experimental manipulations
      that altered [Na+]i did not have a large impact on the rate of recovery of
      [Ca2+]i. 4. The recovery of [Ca2+]i to baseline was accelerated by the
      mitochondrial Na+-Ca2+ exchange inhibitor CGP-37157, suggesting that the recovery
      rate is influenced by release of Ca2+ from a mitochondrial pool and also that
      variation in the recovery rate is related to the extent of mitochondrial Ca2+
      loading. Kainate did not alter the mitochondrial membrane potential. 5. These
      studies reveal that mitochondria have a central role in buffering neuronal
      [Ca2+]i changes mediated by non-N-methyl-D-aspartate (NMDA) glutamate receptors,
      and that the variation in recovery times following kainate receptor activation
      reflects a variable degree of mitochondrial Ca2+ loading. However, unlike NMDA
      receptor-mediated Ca2+ loads, kainate receptor activation has minimal effects on
      mitochondrial function.

PMID- 9547387
TI  - A mutation in the pore region of HERG K+ channels expressed in Xenopus oocytes
      reduces rectification by shifting the voltage dependence of inactivation.
AB  - 1. The effects of a mutation in the human ether-a-go-go-related gene (HERG)
      (Ser631 to Ala, S631A) on the voltage- and extracellular [K+] dependence of
      inactivation were studied in Xenopus oocytes using two microelectrode and single
      channel voltage-clamp techniques. 2. The voltage required for half-inactivation
      of S631A HERG was 102 mV more positive than for wild-type (WT)-HERG, resulting in
      reduced rectification of the steady-state current-voltage relationship. In
      contrast, the voltage dependence of channel activation was not altered by the
      S631A mutation. These findings indicate that inactivation of HERG channels is not
      linked to activation. 3. Rectification of whole-cell S631A HERG current was
      caused by a voltage-dependent reduction in open probability, and inward
      rectification of the current-voltage relationship of single channels. 4.
      Elevation of extracellular [K+] from 2 to 20 mM shifted the half-point for
      inactivation by +20 mV for WT-HERG, and +25 mV for S631A HERG. Thus, elevated
      [K+]o and the S631A mutation affect HERG inactivation by different mechanisms. 5.
      The S631A mutation altered the ion translocation rate of HERG channels. The
      single channel conductance (gamma) of S631A HERG was 20 pS between -40 and-100
      mV, and 6.0 pS between +40 and +100 mV (120 mM extracellular K+). This compares
      to a gamma of 12.1 and 5.1 pS for WT-HERG channels under the same conditions.

PMID- 9547386
TI  - alpha-Adrenergic effects on Na+-K+ pump current in guinea-pig ventricular
      myocytes.
AB  - 1. The whole-cell patch clamp was employed to study Na+-K+ pump current (Ip) in
      acutely isolated myocytes. alpha-Adrenergic receptors were activated with
      noradrenaline (NA) after blocking beta-adrenergic receptors with propranolol. Ip
      was measured as the current blocked by strophanthidin (Str). 2. Activation of
      alpha-receptors by NA increased Ip in a concentration-dependent manner. The K0.5
      depended on intracellular calcium ([Ca2+]i), however maximal stimulation did not.
      At 15 nM [Ca2+]i the K0.5 was 219 nM NA whereas at 1.4 microM [Ca2+]i it was 3
      nM. 3. The voltage dependence of Ip was not shifted by NA at either high or low
      [Ca2+]i. At each voltage, maximal stimulation of Ip was 14-15 %. 4. Staurosporine
      (St), an inhibitor of protein kinase C (PKC), eliminated the alpha-receptor
      mediated stimulation of Ip at either high or low[Ca2+]i. 5. The stimulation of Ip
      was independent of changes in intracellular sodium or external potassium
      concentrations, and did not reflect a change in affinity for Str. 6.
      Phenylephrine, methoxamine and metaraminol, three selective alpha1-adrenergic
      agonists, stimulate Ip in a similar manner to NA. Stimulation of Ip by NA was
      eliminated by prazosin, an alpha1-antagonist, but was unaffected by yohimbine, an
      alpha2-antagonist. 7. We conclude noradrenaline activates ventricular alpha1
      receptors, which are specifically coupled via PKC to increase Na+-K+ pump
      current. The sensitivity of the coupling is [Ca2+]i dependent, however the
      maximal increase in pump current is [Ca2+]i and voltage independent.

PMID- 9547388
TI  - Electrophysiological characterization of Na+ currents in acutely isolated human
      hippocampal dentate granule cells.
AB  - 1. Properties of voltage-dependent Na+ currents were investigated in forty-two
      dentate granule cells (DGCs) acutely isolated from the resected hippocampus of
      twenty patients with therapy-refractory temporal lobe epilepsy (TLE) using the
      whole-cell patch-clamp technique. 2. Depolarizing voltage commands elicited
      large, rapidly activating and inactivating Na+ currents (140 pS microm-2; 163 mM
      extracellular Na+) that were reduced in amplitude by lowering the Na+ gradient
      (43 mM extracellular Na+). At low temperatures (8-12 C), the time course of Na+
      currents slowed and could be well described by the model of Hodgkin & Huxley. 3.
      Na+ currents were reversibly blocked by tetrodotoxin (TTX) and saxitoxin (STX)
      with a half-maximal block of 4.7 and 2.6 nM, respectively. In order to reduce
      series resistance errors, the Na+ current was partially blocked by low toxin
      concentrations (10-15 nM) in the experiments described below. Under these
      conditions, Na+ currents showed a threshold of activation of about -50 mV, and
      the voltages of half-maximal activation and inactivation were -29 and -55 mV,
      respectively. 4. The time course of recovery from inactivation could be described
      with a double-exponential function (time constants, 3-20 and 60-200 ms). The
      rapid and slow time constants showed a distinct voltage dependence with maximal
      values around -55 and -80 mV, respectively. These properties contributed to a
      reduction of the Na+ currents during repetitive stimulation that was more
      pronounced with higher stimulation frequencies and also showed a dependence on
      the holding potential. 5. In summary, the most striking features of DGC Na+
      currents were the large current density and the presence of a current component
      showing a slow recovery from inactivation. Our data provide a basis for
      comparison with properties of Na+ currents in animal models of epilepsy, and for
      the study of drug actions in therapy-refractory epilepsy.

PMID- 9547389
TI  - Regulation of Na+ channels by luminal Na+ in rat cortical collecting tubule.
AB  - 1. The idea that luminal Na+ can regulate epithelial Na+ channels was tested in
      the cortical collecting tubule of the rat using whole-cell and single-channel
      recordings. Here we report results consistent with the idea of Na+ self
      inhibition. 2. Macroscopic amiloride-sensitive currents (INa) were measured by
      conventional whole-cell clamp. INa was a saturable function of external Na+
      concentration ([Na+]o) with an apparent Km of 9 mM. Single channel currents (iNa)
      were measured in cell-attached patches. iNa increased with pipette Na+
      concentration with an apparent Km of 48 mM. Since INa = (iNa)NPo, the different
      Km values imply that the channel density (N) and/or open probability (Po)
      increase as [Na+]o decreases. Reduction of [Na+]o after increasing intracellular
      Na+ concentration also increased the outward amiloride-sensitive conductance,
      consistent with activation of the Na+ channels. 3. The underlying mechanism was
      studied by changing pipette Na+ concentration while recording from cell-attached
      patches. No increase in NPo was observed, suggesting that the effect is not a
      direct interaction between [Na+]o and the channel. 4. [Na+]o was varied outside
      the patch-clamp pipette while recording from cell-attached patches. When
      amiloride was in the bath to prevent Na+ entry, no change in NPo was observed. 5.
      Activation of the channels by hyperpolarization was observed with 140 mM Na+o but
      not with 14 mM Na+o. 6. The results are consistent with the concept of self
      inhibition of Na+ channels by luminal Na+. Activation of the channels by lowering
      [Na+]o is not additive with that achieved by hyperpolarization.

PMID- 9547390
TI  - Role of domain I of neuronal Ca2+ channel alpha1 subunits in G protein
      modulation.
AB  - 1. We studied the G protein inhibition of heteromultimeric neuronal Ca2+ channels
      by constructing a series of chimeric channels between the strongly modulated
      alpha1B subunit and the alpha1E(rbEII) subunit, which showed no modulation. 2. In
      parallel studies, alpha1 subunit constructs were co-expressed together with the
      accessory Ca2+ channel alpha2-delta and beta2a subunits in mammalian (COS-7)
      cells and Xenopus oocytes. G protein inhibition of expressed Ca2+ channel
      currents was induced by co-transfection of Gbeta1 and Ggamma2 subunits in COS-7
      cells or activation of co-expressed dopamine (D2) receptors by quinpirole (100
      nM) in oocytes. 3. The data indicate that transfer of the alpha1B region
      containing the N-terminal, domain I and the I-II loop (i.e. the alpha1B1-483
      sequence), conferred G protein modulation on alpha1E(rbEII), both in terms of a
      slowing of activation kinetics and a reduction in current amplitude. 4. In
      contrast, the data are not consistent with the I-II loop and/or the C-terminal
      forming a unique site for G protein modulation.

PMID- 9547391
TI  - The transient outward current in mice lacking the potassium channel gene Kv1.4.
AB  - 1. The transient outward current (Ito) plays a prominent role in the
      repolarization phase of the cardiac action potential. Several K+ channel genes,
      including Kv1.4, are expressed in the heart, produce rapidly inactivating
      currents when heterologously expressed, and may be the molecular basis of Ito. 2.
      We engineered mice homozygous for a targeted disruption of the K+ channel gene
      Kv1.4 and compared Ito in wild-type (Kv1.4+/+), heterozygous (Kv1.4+/-) and
      homozygous 'knockout' (Kv1.4-/-) mice. Kv1.4 RNA was truncated in Kv1.4-/- mice
      and protein expression was absent. 3. Adult myocytes isolated from Kv1.4+/+,
      Kv1.4+/- and Kv1.4-/- mice had large rapidly inactivating outward currents. The
      peak current densities at 60 mV (normalized by cellular capacitance, in pA pF-1;
      means +/- s.e.m.) were 53.8 +/- 5. 3, 45.3 +/- 2.2 and 44.4 +/- 2.8 in cells from
      Kv1.4+/+, Kv1.4+/- and Kv1.4-/- mice, respectively (P < 0.02 for Kv1.4+/+ vs.
      Kv1.4-/-). The steady-state values (800 ms after the voltage clamp step) were
      30.9 +/- 2.9, 26.9 +/- 3.8 and 23.5 +/- 2.2, respectively (P < 0.02 for Kv1.4+/+
      vs. Kv1.4-/-). The inactivating portion of the current was unchanged in the
      targeted mice. 4. The voltage dependence and time course of inactivation were not
      changed by targeted disruption of Kv1.4. The mean best-fitting V (membrane
      potential at 50 % inactivation) values for myocytes from Kv1.4 +/+, Kv1.4+/- and
      Kv1. 4-/- mice were -53.5 +/- 3.7, -51.1 +/- 2.6 and -54.2 +/- 2.4 mV,
      respectively. The slope factors (k) were -10.1 +/- 1.4, -8.8 +/- 1.4 and -9.5 +/-
      1.2 mV, respectively. The fast time constants for development of inactivation at 
      30 mV were 27.8 +/- 2.2, 26.2 +/- 5. 1 and 19.6 +/- 2.1 ms in Kv1.4+/+, Kv1.4+/-
      and Kv1.4-/- myocytes, respectively. At +30 mV, they were 35.5 +/- 2.6, 30.0 +/-
      2.1 and 28. 7 +/- 1.6 ms, respectively. The time constants for the rapid phase of
      recovery from inactivation at -80 mV were 32.5 +/- 8.2, 23.3 +/- 1.8 and 39.0 +/-
      3.7 ms, respectively. 5. Nearly the entire inactivating component as well as more
      than 60 % of the steady-state outward current was eliminated by 1 mM 4
      aminopyridine in Kv1.4+/+, Kv1.4+/- and Kv1.4-/- myocytes. 6. Western blot
      analysis of heart membrane extracts showed no significant upregulation of the Kv4
      subfamily of channels in the targeted mice. 7. Thus, Kv1.4 is not the molecular
      basis of Ito in adult murine ventricular myocytes.

PMID- 9547392
TI  - Contribution of the Kv3.1 potassium channel to high-frequency firing in mouse
      auditory neurones.
AB  - 1. Using a combination of patch-clamp, in situ hybridization and computer
      simulation techniques, we have analysed the contribution of potassium channels to
      the ability of a subset of mouse auditory neurones to fire at high frequencies.
      2. Voltage-clamp recordings from the principal neurones of the medial nucleus of
      the trapezoid body (MNTB) revealed a low-threshold dendrotoxin (DTX)-sensitive
      current (ILT) and a high-threshold DTX-insensitive current (IHT). 3. IHT
      displayed rapid activation and deactivation kinetics, and was selectively blocked
      by a low concentration of tetraethylammonium (TEA; 1 mM). 4. The physiological
      and pharmacological properties of IHT very closely matched those of the Shaw
      family potassium channel Kv3.1 stably expressed in a CHO cell line. 5. An mRNA
      probe corresponding to the C-terminus of the Kv3.1 channel strongly labelled MNTB
      neurones, suggesting that this channel is expressed in these neurones. 6. TEA did
      not alter the ability of MNTB neurones to follow stimulation up to 200 Hz, but
      specifically reduced their ability to follow higher frequency impulses. 7. A
      computer simulation, using a model cell in which an outward current with the
      kinetics and voltage dependence of the Kv3.1 channel was incorporated, also
      confirmed that the Kv3.1- like current is essential for cells to respond to a
      sustained train of high-frequency stimuli. 8. We conclude that in mouse MNTB
      neurones the Kv3.1 channel contributes to the ability of these cells to lock
      their firing to high-frequency inputs.

PMID- 9547393
TI  - Bilaterally evoked monosynaptic EPSPs, NMDA receptors and potentiation in rat
      sympathetic preganglionic neurones in vitro.
AB  - 1. Whole-cell patch clamp and intracellular recordings were obtained from 190
      sympathetic preganglionic neurones (SPNs) in spinal cord slices of neonatal rats.
      Fifty-two of these SPNs were identified histologically as innervating the
      superior cervical ganglion (SCG) by the presence of Lucifer Yellow introduced
      from the patch pipette and the appearance of retrograde labelling following the
      injection of rhodamine-dextran-lysine into the SCG. 2. Electrical stimulation of
      the ipsilateral (n = 71) or contralateral (n = 32) lateral funiculi (iLF and cLF,
      respectively), contralateral intermediolateral nucleus (cIML, n = 41) or
      ipsilateral dorsal horn (DH, n = 34) evoked EPSPs or EPSCs that showed a constant
      latency and rise time, graded response to increased stimulus intensity, and no
      failures, suggesting a monosynaptic origin. 3. In all neurones tested (n = 60),
      fast rising and decaying components of EPSPs or EPSCs evoked from the iLF, cLF,
      cIML and DH in response to low-frequency stimulation (0.03-0.1 Hz) were sensitive
      to non-NMDA receptor antagonists. 4. In approximately 50 % of neurones tested (n
      = 29 of 60), EPSPs and EPSCs evoked from the iLF, cLF, cIML and DH during low
      frequency stimulation were reduced by NMDA receptor antagonists. In the remaining
      neurones, an NMDA receptor antagonist-sensitive EPSP or EPSC was revealed only in
      magnesium-free bathing medium, or following high-frequency stimulation. 5. EPSPs
      evoked by stimulation of the iLF exhibited a sustained potentiation of the peak
      amplitude (25.3 +/- 11.4 %) in six of fourteen SPNs tested following a brief high
      frequency stimulus (10-20 Hz, 0.1-2 s). 6. These results indicate that SPNs,
      including SPNs innervating the SCG, receive monosynaptic connections from both
      sides of the spinal cord. The neurotransmitter mediating transmission in some of
      the pathways activated by stimulation of iLF, cLF, cIML and DH is glutamate
      acting via both NMDA and non-NMDA receptors. Synaptic plasticity is a feature of
      glutamatergic transmission in some SPNs where EPSPs are potentiated following a
      brief high-frequency stimulus. Our data also suggest a differential expression of
      NMDA receptors by these neurones.

PMID- 9547395
TI  - Synaptic currents at individual connections among stellate cells in rat
      cerebellar slices.
AB  - 1. Unitary inhibitory synaptic connections among stellate cells were studied in
      rat cerebellar slices. Presynaptic action potentials and inhibitory postsynaptic
      currents (IPSCs) were simultaneously recorded by loose cell-attached and tight
      seal whole-cell recording, respectively. 2. Several types of synaptic connections
      were distinguished on the basis of the shape of the amplitude distribution of
      successfully evoked currents. For simple synapses, which presumably arise at
      single release sites, these histograms could be fitted to a single Gaussian (5
      cases). In four additional cases a small amplitude component (< 50 pA) was
      superimposed to a single Gaussian peak. The small events had slow rise times and
      widely distributed amplitudes. Finally eleven histograms showed two or more
      Gaussian components and were classified as complex connections. 3. Failure rates
      ranged from 0.06 to 0.85 for unitary connections (n = 20) and from 0.59 to 0.78
      for simple synapses (n = 5). 4. Coefficient of variation values derived from
      Gaussian fits to simple synapse histograms ranged between 0.20 and 0.38 (n = 5).
      5. In simple synapses peak current amplitudes were positively correlated to both
      current rise time and decay half-width. 6. Intervals between presynaptic action
      potentials were widely distributed. During stationary periods there was no
      correlation between interspike interval and amplitude size, success rate or
      latency. In some experiments, episodes with shorter interspike intervals were
      observed. During these periods, amplitude and success rate decreased, and the
      latency increased. Thus, IPSC characteristics depend on the mean frequency of
      presynaptic spikes, but not on random fluctuations of interspike intervals during
      stationary periods.

PMID- 9547394
TI  - Ionotropic and metabotropic activation of a neuronal chloride channel by
      serotonin and dopamine in the leech Hirudo medicinalis.
AB  - 1. Cl- channels on the pressure-sensitive (P) neuron in the leech are directly
      activated by synaptic release of serotonin (5-HT) and are indirectly stimulated
      by the cAMP second messenger pathway, suggesting an unusual dual regulation of
      the channels. We have investigated the mode of action of 5-HT and dopamine (DA)
      on a Cl- channel in adult P cells in culture by recording from cell-attached
      patches. 2. 5-HT increased Cl- channel activity only when included in the
      recording pipette and not when applied in the bath. 3. Pipette or, more
      effectively, bath application of DA led to an increase in Cl- channel activity.
      This effect was blocked by the potent and specific dopaminergic (DA1) receptor
      blocker, SCH-23390. 4. The stimulation by DA, but not by 5-HT, was also blocked
      by the cAMP-dependent protein kinase A (PKA) inhibitor Rp-cAMP and was mimicked
      by the membrane-permeant cAMP analogue dibutyryl cAMP (db-cAMP). 5. Our results
      show that 5-HT directly gates a Cl- channel that is also activated by DA via the
      cAMP pathway. This study demonstrates that a ligand-gated channel can be
      independently operated by another transmitter acting via a second messenger
      pathway.

PMID- 9547396
TI  - Differential effects of noradrenaline on evoked, spontaneous and miniature IPSCs
      in rat cerebellar stellate cells.
AB  - 1. The modulation by noradrenaline (NA) of synapses among stellate cells was
      investigated in rat cerebellar slices by using presynaptic loose cell-attached
      recording and postsynaptic whole-cell recording. 2. NA increased the frequency of
      spontaneous IPSCs recorded from stellate cells without changing their mean
      amplitude. 3. NA increased the firing rate of stellate cells. This effect
      persisted after blocking ionotropic glutamate receptors and GABA receptors,
      indicating that it was independent of synaptic input. 4. The effects of NA on
      action potential frequency were mimicked by the beta-receptor agonist
      isoprenaline but not by the alpha-receptor agonist 6-fluoro noradrenaline, and
      they were not blocked by the alpha-receptor antagonist phentolamine, indicating
      that they were mediated by beta-receptors. 5. In paired recordings of connected
      stellate cells, NA slightly decreased the success rate of synaptic transmission.
      A small decrease in mean IPSC amplitude (excluding failures) and a slight
      increase in latency were also observed in NA. 6. These results show that, while
      NA increases the number of action potential-dependent IPSCs by increasing the
      firing rate of stellate cells, it actually reduces the probability of evoked
      release. Since previous studies showed that NA increases the rate of miniature
      IPSCs in this preparation, we conclude that different mechanisms underly the
      modulation by NA of action potential-dependent and action potential-independent
      transmitter release.

PMID- 9547397
TI  - Blockade of synaptic inhibition within the pre-Botzinger complex in the cat
      suppresses respiratory rhythm generation in vivo.
AB  - 1. The role of synaptic inhibition in respiratory rhythm generation was analysed
      by microinjections of GABAA and glycine receptor antagonists into the bilateral
      pre-Botzinger complex (PBC) of anaesthetized cats. Central respiratory activity
      was monitored by phrenic nerve recordings. 2. Bilateral injections of bicuculline
      (50 or 100 microM) irreversibly slowed respiratory frequency and induced
      apneustic patterns. 3. Bilateral injections of strychnine (50 or 100 microM)
      greatly reduced phrenic burst amplitudes leading to increased burst frequency or
      irreversibly blocked rhythmic phrenic discharges. After unilateral tetrodotoxin
      (TTX) blockade in the PBC, strychnine injection into the contralateral PBC
      blocked rhythmic phrenic discharges. 4. Bilateral blockade of both GABAergic and
      glycinergic inhibition abolished rhythmic burst discharges and only tonic phrenic
      activity remained. Such tonic activity was blocked only by TTX (1 microM). 5.
      Potentiation of synaptic inhibition by the serotonin 1A receptor agonist 8
      hydroxydipropylaminotetralin (8-OH-DPAT; 50 microM) restored rhythmic activity
      only when given shortly after strychnine and bicuculline applications. It was,
      however, ineffective after blockade of synaptic inhibition was complete. 6. The
      study demonstrates the significance of synaptic inhibition in the process of
      respiratory generation in the adult cat in vivo.

PMID- 9547398
TI  - AMPA receptor activation and phosphatase inhibition affect neonatal rat
      respiratory rhythm generation.
AB  - 1. We investigated the role of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA) receptors and their regulation in affecting respiratory-related
      neurones in a neonatal rat medullary slice that spontaneously generates
      respiratory-related rhythm and motor output in the hypoglossal (XII) nerve. 2.
      Bath application of the AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8
      methylenedioxy-5H-2, 3-benzodiazepine (GYKI) completely blocked XII nerve
      activity, as well as respiratory-related synaptic drives in neurones within the
      preBotzinger Complex (preBotC), site of rhythm generation in the slice. 3. Local
      application of GYKI to the preBotC blocked respiratory rhythm. Local application
      of AMPA to the preBotC increased rhythm frequency and depolarized respiratory
      related neurones. 4. In the presence of tetrodotoxin (TTX), GYKI completely
      blocked the inward current induced by local application of AMPA, but not that
      induced by kainate. 5. Local application of okadaic acid, a membrane-permeable
      inhibitor of phosphatase 1 and 2A, to the preBotC increased the frequency of
      respiratory motor discharge. 6. Intracellular application of microcystin, a
      membrane-impermeable inhibitor of phosphatase 1 and 2A, enhanced endogenous
      inspiratory drive and exogenous AMPA-induced current (in the presence of TTX) in
      preBotC inspiratory neurones. Both the enhanced inspiratory drive and the
      increased AMPA-induced current were completely blocked by GYKI. 7. We suggest
      that AMPA receptor activation and AMPA receptor modulation by phosphorylation are
      crucial for the rhythm generation within the preBotC.

PMID- 9547399
TI  - Neutralization of pyrogen-induced tumour necrosis factor by its type 1 soluble
      receptor in guinea-pigs: effects on fever and interleukin-6 release.
AB  - 1. A soluble form of the tumour necrosis factor (TNF) type 1 receptor (referred
      to as TNF binding protein, TNF-bp) at a dose of 1 mg per animal, or an equivalent
      volume of solvent, was injected together with 10 microg kg-1 lipopolysaccharide
      (LPS) or 50 microg kg-1 muramyl-dipeptide (MDP) directly into the arterial
      circulation of guinea-pigs and the effects on circulating TNF or interleukin-6
      (IL-6) and on abdominal temperature were studied. 2. At 15 or 60 min after
      injection, LPS-induced and MDP-induced circulating TNF was below the detection
      limit of the assay and thus completely neutralized in animals treated with TNF
      bp. In the control group, TNF was still below the limit of detection in most
      animals 15 min after LPS was injected; in some animals small traces of TNF could
      already be detected at that time. However, 60 min after administration of LPS,
      large amounts of TNF (19508 +/- 4682 pg ml-1) were measured in the control group.
      MDP-induced TNF in plasma was below the limit of detection 15 min after MDP was
      injected, and rose to 10862 +/- 3029 pg ml-1 60 min after injection. 3. Low
      levels of circulating IL-6 (20-40 international units (IU) ml-1) were measured in
      all groups of animals 15 min after injection of LPS or MDP. This value
      corresponds to the baseline activity of IL-6 in plasma of guinea-pigs. One hour
      after administration of LPS, IL-6 rose to 5442 +/- 1662 IU ml-1 in the control
      group and to a significantly lower value of 1485 +/- 179 IU ml-1 in guinea-pigs
      treated with TNF-bp. One hour after injection of MDP, circulating IL-6 was 2614
      +/- 506 IU ml-1 in the control group, while the corresponding value in animals
      treated with TNF-bp again was significantly lower (873 +/- 312 IU ml-1). 4. The
      second phase of the characteristic biphasic LPS fever in guinea-pigs was
      significantly attenuated in animals treated with TNF-bp. The shorter first phase
      of the febrile response to LPS was identical in both groups of animals. 5. The
      late phase of MDP-induced fever (7-22 h after injection) was depressed by
      treatment with TNF-bp, while the first phase of MDP-induced fever (0-7 h after
      injection) was significantly enhanced by the neutralization of TNF by TNF-bp.

PMID- 9547400
TI  - Harmonic distortion on the basilar membrane in the basal turn of the guinea-pig
      cochlea.
AB  - 1. Mechanical responses to pure-tone stimuli were recorded from the basilar
      membrane in the basal turn of the guinea-pig cochlea using a displacement
      sensitive laser interferometer. The harmonic content of the responses was
      evaluated using Fourier analysis. 2. Harmonic distortion products were observed
      in many of the basilar membrane responses. Response components locked to twice
      the frequency of the stimulus (i.e. 2F0) were the largest of the distortion
      products. 3. The second harmonic responses showed a bimodal frequency
      distribution at low to moderate sound pressure levels: one peak occurred around
      the preparation's best or most sensitive frequency (i.e. when F0 approximately 17
      kHz), and another occurred around one-half of the best frequency (when F0
      approximately 8.5 kHz). 4. The absolute levels of most distortion products
      increased progressively with increasing stimulus strength. When expressed with
      respect to the levels of the fundamental responses, however, the distortion
      levels usually decreased with increasing stimulus strength. 5. The levels of the
      distortion decreased (in both absolute and relative terms) with deterioration in
      the physiological condition of the cochlea. 6. Maximum second harmonic distortion
      levels amounted to approximately 3.5 and approximately 28 % of the fundamental
      responses to tones near and below the best frequency, respectively. 7. The above
      findings are shown to be consistent with a highly simplified model of cochlear
      mechanics which incorporates an asymmetric, saturating non-linearity in a
      positive feedback loop.

PMID- 9547401
TI  - Induction of antioxidant enzyme activity by hyperoxia (60 % O2) in the developing
      chick embryo.
AB  - 1. At premature birth, man and animals are exposed to relatively high oxygen
      levels, compared with intra-uterine conditions, at a time when their antioxidant
      enzyme (AOE) system is still immature. Using the chick embryo as a study model,
      we investigated changes in the AOE system in response to hyperoxia applied at
      different time points during the incubation period. Relations between hyperoxia
      and AOE activity were studied in selected organs (brain, heart, liver, intestine
      and lungs) of developing chick embryos (during the second half of the incubation
      period). 2. Incubated White Leghorn eggs were divided into four groups: control
      (n = 100) and three test groups exposed for 48 h to 60 % O2 on day 10 (test group
      1, n = 80), day 14 (test group 2, n = 60) and day 18 (test group 3, n = 30).
      Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) enzyme
      activities were measured in homogenates of the brain, heart, liver, intestine and
      lungs. 3. Exposure to hyperoxia at different time points during incubation
      resulted in a 2- to 10-fold increase in SOD activity in all organs except the
      brain. Catalase and GPx enzyme activities were only induced in test group 1, 48 h
      after initiation of hyperoxia. 4. In the developing chick embryo, hyperoxia can
      produce a temporary induction of AOE activity, which is dependent on the AOE,
      organ, incubation time and time point of exposure.

PMID- 9547402
TI  - The role of endothelin-A receptors in cardiovascular responses to acute
      hypoxaemia in the late gestation sheep fetus.
AB  - 1. In unanaesthetized chronically instumented fetal sheep (118-121 days
      gestation) we investigated the effect of acute isocapnic hypoxaemia (arterial
      Po2, 12.5 +/- 0.6 mmHg) on heart rate (FHR), mean systemic arterial blood
      pressure (MABP), carotid and femoral blood flows (CBF and FBF, respectively), and
      carotid and femoral vascular resistances (CVR and FVR, respectively) with the
      infusion of either the endothelin-A (ETA) receptor antagonist FR139317, or saline
      vehicle. 2. During normoxaemia FHR (P < 0.05) and CBF (P < 0. 01) were greater,
      and CVR (P < 0.01) was lower with FR139317 than with vehicle infusion. CVR
      remained lower with FR139317 than with vehicle infusion during hypoxaemia (P <
      0.01) and recovery (P < 0. 05). During hypoxaemia the rapid initial bradycardia,
      the increase in MABP and FVR and the decrease in FBF were similar with vehicle
      and FR139317 infusion. In both groups plasma endothelin-1 concentration ([ET-1])
      was unaltered by hypoxaemia. The increase in CBF during hypoxaemia with vehicle
      (P < 0.01) was absent with FR139317 infusion. 3. Thus in the late gestation ovine
      fetus endogenous ET-1 modulates basal FHR, CBF and CVR via ETA receptors.
      Modulation of CBF and CVR persists during hypoxaemia but ETA receptors do not
      appear to contribute to the decrease in femoral blood flow measured during acute
      hypoxaemia.

PMID- 9547404
TI  - Nitrite adulteration of workplace urine drug-testing specimens. I. Sources and
      associated concentrations of nitrite in urine and distinction between natural
      sources and adulteration.
AB  - The active ingredient in the commercial workplace urine drug-testing adulterant,
      Klear, was previously determined to be nitrite ion. Nitrite adulteration
      compromises the confirmation of some drugs, notably the marijuana metabolite. A
      previously reported bisulfite step overcomes some nitrite adulteration, but it
      cannot do so in every case, which leaves the laboratory to report the specimen as
      not suitable for testing. Unlike many other adulterants, nitrite is found in
      normal urine at low concentrations. In order to defend a report of nitrite
      adulteration, it is necessary to provide evidence that the amount of nitrite in a
      workplace urine specimen could not arise by normal means. The objectives of this
      study were to identify all sources of nitrite in urine and the range of
      concentrations associated with these sources and to determine if nitrite
      adulteration can be supported based upon a quantitative result. The scientific
      literature was reviewed for internal and external sources of nitrite and their
      concentration ranges and are reported. The following specimens were obtained and
      nitrite concentrations measured by a spectrophotometric method: clinical
      specimens nitrite positive by test strip (< 15 micrograms/mL); specimens culture
      positive for nitrate-reducing microorganisms (< 36 micrograms/mL); specimens from
      patients on medications that may metabolize to nitrite (< 6 micrograms/mL); and
      drug-test specimens, both negative (< 130 micrograms/mL) and others that appeared
      to be adulterated with nitrite (range 1910-12,200 micrograms/mL, mean 5910). The
      literature and the nitrite measurements of this study indicate a substantial
      difference between concentrations from natural sources compared with
      adulteration. A quantitative measurement of nitrite by a well-structured assay
      can provide scientifically valid and forensically defensible proof of
      adulteration with a nitrite-containing substance.

PMID- 9547403
TI  - Exercise metabolism in human skeletal muscle exposed to prior eccentric exercise.
AB  - 1. The effects of unaccustomed eccentric exercise on exercise metabolism during a
      subsequent bout of graded concentric exercise were investigated in seven healthy
      male subjects. Arterial and bilateral femoral venous catheters were inserted 2
      days after eccentric exercise of one thigh (eccentric thigh) and blood samples
      were taken before and during graded two-legged concentric knee-extensor exercise.
      Muscle biopsies were obtained from the eccentric and control vastus lateralis
      before (rest) and after (post) the concentric exercise bout. 2. Maximal knee
      extensor concentric exercise capacity was decreased by an average of 23 % (P <
      0.05) in the eccentric compared with the control thigh. 3. The resting muscle
      glycogen content was lower in the eccentric thigh than in the control thigh (402
      +/- 30 mmol (kg dry wt)-1 vs. 515 +/- 26 mmol (kg dry wt)-1, means +/- s.e.m., P
      < 0.05), and following the two-legged concentric exercise this difference
      substantially increased (190 +/- 46 mmol (kg dry wt)-1 vs. 379 +/- 58 mmol (kg
      dry wt)-1, P < 0.05) despite identical power and duration of exercise with the
      two thighs. 4. There was no measurable difference in glucose uptake between the
      eccentric and control thigh before or during the graded two-legged concentric
      exercise. Lactate release was higher from the eccentric thigh at rest and, just
      before termination of the exercise bout, release of lactate decreased from this
      thigh (suggesting decreased glycogenolysis), whereas no decrease was found from
      the contralateral control thigh. Lower glycerol release from the eccentric thigh
      during the first, lighter part of the exercise (P < 0.05) suggested impaired
      triacylglycerol breakdown. 5. At rest, sarcolemmal GLUT4 glucose transporter
      content and glucose transport were similar in the two thighs, and concentric
      exercise increased sarcolemmal GLUT4 content and glucose transport capacity
      similarly in the two thighs. 6. It is concluded that in muscle exposed to prior
      eccentric contractions, exercise at a given power output requires a higher
      relative workload than in undamaged muscle. This increases utilization of the
      decreased muscle glycogen stores, contributing to decreased endurance.

PMID- 9547405
TI  - A rapid, sensitive method for the quantitation of N-acetyl-S-(2-hydroxyethyl)-L
      cysteine in human urine using isotope-dilution HPLC-MS-MS.
AB  - Because of increasing concern about exposure to carcinogens and other toxicants,
      reliable methods for biological monitoring of potentially exposed populations
      must be developed. For biological monitoring to be useful, appropriate biomarkers
      of exposures to xenobiotics must be identified, and sensitive, specific methods
      for quantifying the targeted biomarker must be developed. We have developed a
      sensitive and selective method for the analysis of N-acetyl-S-(2-hydroxyethyl)-L
      cysteine (HEMA), urinary metabolite of at least three different known human
      carcinogens (vinyl chloride, ethylene oxide, and ethylene dibromide). The method
      uses strong anion-exchange solid-phase extraction and isotope-dilution high
      performance liquid chromatography-tandem mass spectrometry. Our method is simple
      and is not labor intensive; the preparation time per sample is less than 10 min.
      Because urine samples vary in both their concentration and ion strength,
      intersample variability in HEMA recovery during the extraction is large. To
      overcome this inherent limitation, we use the isotope-dilution technique, which
      allows a complete correction for the extraction recovery for each sample. The
      limit of detection of the method is 0.68 microgram/L in a 1-mL urine sample with
      a coefficient of variation of 22% (determined by replicate analyses at both 4 and
      11 micrograms/L) and an accuracy indistinguishable from 100%. Preliminary
      analyses of urine from a population with no known overt exposure to the parent
      toxicants show a frequency of detection of approximately 75%, which indicates
      that this method has the sensitivity to detect urinary HEMA derived from
      environmental exposure. We are currently using this method to establish a
      reference range of background exposure to these toxicants in the U.S. population.

PMID- 9547406
TI  - A barbiturate screening assay for the Abbott AxSYM analyzer.
AB  - A fluorescence polarization immunoassay for barbiturates on the Abbott AxSYM
      analyzer is described. The assay displayed dilution linearity up to 1200 ng/mL;
      coefficients of variation varied from 5.96 to 8.61%; recovery varied from 94.9 to
      105.3%; and sensitivity was less than 40 ng/mL. Good correlation between the
      standard six- and factory two-point calibration methods was observed. The
      Immunoassay demonstrated good cross-reactivity to several commonly prescribed
      barbiturates; low cross-reactivity with structurally similar compounds; low
      interference from endogenous substances, dyes, preservatives, and several
      commonly available adulterants; and good correlation with the TDx Barbiturate
      Urine assay.

PMID- 9547407
TI  - Detection and determination of theobromine and caffeine in urine after
      administration of chocolate-coated peanuts to horses.
AB  - The objective of this study was to determine the urinary excretion of
      methylxanthines in horses following ingestion of chocolate over eight days. The
      study was performed in response to gas chromatography-mass spectrometry (GC-MS)
      confirmation of the presence of caffeine in a positive urine test in a racehorse.
      The trainer of the horse alleged that he often administered chocolate-coated
      peanuts as treats to his horses, and he believed that the ingestion of chocolate
      was responsible for the positive urine test. The urinary excretion of theobromine
      and caffeine after the ingestion of chocolate-coated peanuts was investigated in
      three horses. Enzyme-linked immunoassay (ELISA), high-performance liquid
      chromatography (HPLC), and GC-MS assays were performed on all urine specimens.
      Theobromine (HPLC) was detected for 72 h and caffeine (GC-MS) for 48 h after
      chronic ingestion of chocolate-coated peanuts. Methylxanthines were detected by
      ELISA for 120 h after administration of chocolate.

PMID- 9547408
TI  - Survey on drugs-of-abuse testing in the European Union.
AB  - A survey on the quality of drugs-of-abuse testing in European laboratories was
      performed in 1993 (Part I) and 1994 (Part II). A total of 195 laboratories
      participated in Part I and 228 in Part II. There were 154 repeater laboratories.
      In each part of the survey, six urine samples were sent for analysis under
      routine conditions. A set of reference materials, including deuterated drug
      standard solutions, was provided in Part II of the survey for optimization of
      analytical procedures. Screening for groups of substances was mainly performed by
      immunological techniques. Rates of false-positive (FP) results were 0 and 0.5%,
      respectively, in Parts I and II, and rates of false-negative (FN) results were
      7.7% in Part I and 3.4% in Part II. Identification and quantitation of specific
      substances was mainly carried out by chromatographic methods, particularly gas
      chromatography coupled to mass spectrometry. Application of chromatographic
      methods showed a lack of sensitivity (14.9% and 16.7% FN in Parts I and II,
      respectively) and a lack of specificity (0.8% FP in Part I versus 1.1% in Part
      II). Repeater laboratories improved their results (17.4% FN in Part I versus
      14.2% Part II). The improvement of repeater laboratories emphasizes the need of
      external quality control programs. The experience is being used as a basis for a
      recommendation on drug-testing guidelines by a group of European toxicologists.

PMID- 9547410
TI  - The feasibility of the detection and quantitation of beta-adrenergic blockers by
      solid-phase extraction and subsequent derivatization with methaneboronic acid.
AB  - Urine specimens containing 11 common beta blockers were processed using solid
      phase extraction technology to extract the drugs from the urine matrix, then
      converted to their cyclic methaneboronates by treatment with methaneboronic acid
      in ethyl acetate. The compounds tested included acebutolol, atenolol, alprenolol,
      bisoprolol, betaxolol, carteolol, penbutolol, propranolol, pindolol, timolol,
      nadolol, sotalol, labetolol, metoprolol, and oxprenolol. The extraction
      efficiencies were greater than 90% for all drugs tested. The cyclic
      methaneboronates formed by this procedure generally possessed good
      chromatographic properties. The mass spectral behavior of the methaneboronates
      was excellent, with all compounds containing several high mass fragments and
      every tested compound possessing a unique mass spectrum.

PMID- 9547409
TI  - Screening procedure for beta-adrenergic drugs in sports drug testing by
      immunological methods.
AB  - A systematic study of the cross-reactivities of beta-adrenergic agonists and
      antagonists and their metabolites with an ELISA test designed to detect
      terbutaline and other beta 2-agonists has been performed in order to evaluate the
      applicability of this immunological test as screening method in routine human
      sports drug testing. Concentration response curves were calculated. IC50 values
      from 1.7 to 21.5 ng/mL were obtained for beta 2-agonists, and values from 3.1 to
      520.8 ng/mL were obtained for most of the beta-blockers. The highest cross
      reactivity was mainly depending on the amino substituent of the molecules
      although the structure of the aromatic ring was also important. Minor changes in
      the aromatic ring, such as 4-hydroxylation for propranolol, did not largely
      influence the IC50 value. Distribution of control activities (percentage of
      optical density as compared with a blank sample) of urines obtained in controlled
      excretion studies (70 samples) and urines collected after competition in sports
      in which beta-blockers are recommended to be tested (147 samples) showed a very
      small overlapping between the subpopulations of positive and negative samples.
      Cutoff values of 45 or 60% control activity were proposed for routine analysis.
      Sensitivity and specificity values of 92.8 and 98.8%, respectively (cutoff 45%),
      or 98.2 and 95.0%, respectively (cutoff 60%), were obtained. Because the known
      prevalence of positive results of beta-blockers and beta 2-agonists in the target
      population was very low, the predicted percentage of presumptive positive cases
      that would need further confirmation by gas chromatography-mass spectrometry was
      also low, accounting for a 1.48 and 5.28% (for the cutoffs of 45 and 60%,
      respectively) of the total number of samples to be screened by the presented
      ELISA test. Thus, in terms of time and cost savings, the ELISA test is a powerful
      tool for the purpose of screening for beta-adrenergic drugs in human urine.

PMID- 9547411
TI  - Morphine formation from ethylmorphine: implications for drugs-of-abuse testing in
      urine.
AB  - In drugs-of-abuse testing, opiates constitute a delicate and controversial task
      because morphine may occur in urine for several reasons. Ethylmorphine (EtM),
      which is used as an antitussive drug in many countries, is metabolically
      converted to morphine. The present study was performed in order to document intra
      and interindividual differences in morphine formation after single-dose intake
      of EtM at two different doses (25 and 50 mg). The urinary excretion of opiates
      was measured during 48 h with EMIT and gas chromatography-mass spectrometry in 10
      healthy volunteers. The mean values of totally recovered EtM and morphine in
      hydrolyzed urine during 48 h were 42 and 47% of the given dose at high and low
      dose level, respectively. The ratio between total recovered morphine and EtM
      ranged from 19 to 131% with a mean value of 48%. The rate of positive outcome in
      the EMIT opiate-screening assay was 100% during the first 24 h for both doses,
      and it was still high (> or = 67%) in the 24-48 h time interval. It was found
      that the decline in urinary EtM is more rapid than for morphine, which leads to
      an increasing morphine/EtM ratio in urine over time. THe mean value of the
      morphine/EtM ratio was found to be greater than 1 during the 12-24 h interval and
      finally increased to greater than 10. There was an intra-individual concordance
      in morphine/EtM ratio between doses, but there was marked interindividual
      variation. Morphine/EtM ratios that were greater than 1 were only seen when the
      concentration of morphine was below 300 micrograms/mmol creatinine. Our results
      demonstrate that morphine is formed from EtM at a high and variable rate and may
      be present in urine in concentrations greater than those of EtM even shortly
      after drug intake.

PMID- 9547412
TI  - Development and evaluation of immunochromatographic rapid tests for screening of
      cannabinoids, cocaine, and opiates in urine.
AB  - The test principle and the optimization of the reactive ingredients are described
      for the one-step dip and-read immunochromatographic FRONTLINE rapid tests for
      drugs-of-abuse testing in urine samples. In a multicenter evaluation the rapid
      tests were compared with FPIA and EMIT immunoassays. Discrepant results were
      further analyzed by gas chromatography-mass spectrometry methods. In the
      comparison of the cannabinoids rapid tests versus both immunoassays using
      clinical and forensic urine samples (399 versus FPIA and 755 versus EMIT),
      sensitivities and specificities were 97% or better for both comparisons. For
      cocaine, a sensitivity of 100% versus both routine technologies was obtained,
      whereas the specificity was reduced somewhat to 91% because of some cross
      reactivity with metabolites of methadone and of clozapine. Specificity was very
      high for the cocaine rapid tests (98-100%) when applied to urine samples of
      persons not in a methadone maintenance program. Sensitivities and specificities
      for the opiates rapid tests were 99% or better at all sites when compared with
      the routine methods. In the screening of about 1200 clinical urine samples for
      cannabinoids, cocaine or opiates misuse only six samples would have stayed
      undetected by rapid test analyzes. These results show the FRONTLINE assays allow
      a reliable and immediate screening for drugs of abuse.

PMID- 9547413
TI  - Incorporation of isotopically labeled cocaine into human hair: race as a factor.
AB  - In order to evaluate race as a possible factor affecting the incorporation of
      drugs into human hair, 2 mg/kg deuterium-labeled cocaine (cocaine-d5) was
      administered intranasally to nine male non-Caucasian volunteers under controlled
      laboratory conditions. Sequential blood samples were collected for up to three
      days, and scalp hair samples were collected at 24 and 72 h after dosing and at
      monthly intervals for up to 12 months. The samples were then analyzed by gas
      chromatography-mass spectrometry for cocaine-d5 and benzoylegonine-d5 (BZE-d5).
      The amounts of cocaine-d5 found in the hair of these non-Caucasian subjects were
      compared with the amounts of cocaine-d5 found in the hair of Caucasian subjects
      who received the same cocaine dose under identical conditions as part of a study
      we reported previously. The non-Caucasians in the present study had approximately
      2.7 times more cocaine-d5 in their hair than the Caucasian subjects in the
      earlier study. In five of the non-Caucasian subjects, cocaine-d5 could be
      detected in hair within 24 h after dosing. Curiously, we were unable to detect
      any cocaine-d5 in one of the non-Caucasian subject's hair at any time after
      dosing even though cocaine-d5 was in plasma at the expected levels. The results
      from these studies suggest there may be a racial bias in the incorporation of
      cocaine into human hair; however, the data are not conclusive because of the
      relatively small sample size.

PMID- 9547414
TI  - Suicide with the veterinary drug acepromazine.
AB  - A suicide case involving the veterinary drug acepromazine is described. After a
      single-step liquid alkaline extraction, acepromazine was identified in a chest
      cavity blood sample using gas chromatography (GC) with nitrogen-phosphorus (NPD)
      and mass selective detectors. Acepromazine was then quantitated in the blood and
      other postmortem tissues by GC with NPD using chlorpromazine as the internal
      standard. Acepromazine concentrations in the chest-cavity blood, liver, brain,
      and bile were 0.6, 3.0, 0.4, and 6.5 micrograms/mL, respectively. The stomach
      contents contained a total of 2.5 mg acepromazine.

PMID- 9547415
TI  - Recent paramethoxyamphetamine deaths.
AB  - Paramethoxyamphetamine (PMA) is a methoxylated phenethylamine derivative that has
      been used illicitly in Australia since late 1994. It is purportedly sold under
      the guise of "ecstasy", which is the colloquial name for
      methylenedioxymethamphetamine (MDMA). Methods for extraction, identification, and
      quantitation are presented. Toxicology findings in six fatalities involving the
      drug are discussed. Femoral blood PMA levels ranged from 0.24 to 4.9 mg/L (mean,
      2.3 mg/L). Liver PMA levels ranged from 1.4 to 21 mg/kg (mean, 8.9 mg/kg). Other
      amphetamines were found in five of the six cases. Blood PMA levels in three
      nonfatal cases are also presented. PMA appeared to be more toxic than MDMA, and
      blood levels greater than 0.5 mg/L seemed likely to be associated with toxic
      effects.

PMID- 9547417
TI  - Stabilization of blood cyanide.

PMID- 9547416
TI  - 6-acetylmorphine detection in postmortem cerebrospinal fluid.

PMID- 9547418
TI  - Analysis of Hempen Ale for cannabinoids.

PMID- 9547420
TI  - Coping with chronic pain: sources of intrinsic and contextual variability.
AB  - Univariate and multivariate analyses were used to investigate intrinsic and
      contextual sources of coping variability among 90 patients with chronic pain.
      Pain coping strategies were assessed by the subscales of the Coping Strategies
      Questionnaire. Intrinsic variables included demographic characteristics and
      dispositional optimism. Contextual variables included pain-related variables and
      pain control appraisals. In univariate analyses, ethnicity was a statistically
      significant intrinsic source of variability for the praying and hoping coping
      subscale; however, comparisons between pairs of ethnic groups were not
      statistically significant. A multivariate perspective of the data found three
      independent and salient patterns of correlation between the intrinsic and
      contextual variables and coping subscales. These patterns of correlation
      accounted for 96% of the total variance and were conceptualized as optimistic
      active coping, educated rational coping, and optimistic restricted coping. The
      findings raise the prospect that there are intrinsic and contextual explanations
      of coping variability for patients with chronic pain.

PMID- 9547419
TI  - Off-treatment fatigue in breast cancer survivors: a controlled comparison.
AB  - Fatigue is a common and distressing symptom following cancer treatment. Research
      examining "off-treatment" fatigue has been weakened by limited assessments of
      fatigue and lack of suitable comparison groups. The extent of off-treatment
      fatigue following treatment for breast cancer (BC) was examined. Women with BC (n
      = 88; mean, 28 months posttreatment) and age-matched women (n = 88) with benign
      breast problems (BBP), completed a set of fatigue questionnaires at an Initial
      assessment and a 4-month Follow-up assessment. The BC group reported more
      fatigue, more weakness, and less vitality relative to the BBP group at both
      assessments. No relationship was found in the BC group between fatigue and extent
      of treatment or time since treatment completion. While the results document the
      existence of off-treatment fatigue following BC, elucidation of the
      psychobiological processes underlying this symptom and development of clinical
      management strategies remain as challenges for future research.

PMID- 9547421
TI  - Health status in sickle cell disease: examining the roles of pain coping
      strategies, somatic awareness, and negative affectivity.
AB  - People with sickle cell disease (SCD) vary in their pain, activity levels, and
      medical care. We examined how coping (Coping Strategies Questionnaire), somatic
      awareness, and illness worry were related to these health indices in 70 African
      American adults with SCD. Negative Thinking/Passive Adherence and/or somatic
      awareness was positively correlated with pain episode frequency, duration, or
      severity, after controlling for demographics and disease severity and positively
      correlated with activity reduction or hospitalization frequency after also
      controlling for pain. Self-reported negative affectivity was correlated with both
      psychological and SCD measures; and controlling for negative affectivity
      eliminated several, but not all, relationships. Examination of the Negative
      Thinking/Passive Adherence factor suggested a distinction between Negative
      Thinking and Passive Adherence, which was partially supported by their different
      relationships. We conclude that negative thinking, passive coping, and somatic
      awareness are related to several measures of poor health in SCD but that some
      relationships are better accounted for by general measures of negative
      affectivity.

PMID- 9547422
TI  - The evaluation of medical symptoms by patients and doctors.
AB  - This study investigates discrepancy and congruence between doctors and patients
      in their beliefs about the need for medical treatment. One hundred seventy-six
      outpatients and 337 university students rated each of a set of 35 symptoms on the
      urgency with which they would seek medical advice were they experiencing that
      symptom. Sixty-six general practitioners rated the urgency with which a person
      experiencing that symptom should seek medical advice. These symptoms were
      classified as relatively serious or nonserious on the basis of ratings by a
      separate set of doctors. General practitioners perceived a greater overall need
      for treatment than did patients, but this difference was greater for nonserious
      than for serious symptoms. In fact patients perceived treatment to be more urgent
      for three serious symptoms, each potentially indicative of cancer. The observed
      pattern of doctor-patient discrepancies can be explained in terms of the
      availability heuristic. The role of this heuristic in the cognitive dynamics of
      doctor-patient relationships merits future attention.

PMID- 9547424
TI  - The effects of evening light exposure on the sleep of elderly women expressing
      sleep complaints.
AB  - In order to address the typical phase advanced, disturbed sleep of the elderly,
      additional evening light was provided to elderly women by means of a "visor"
      which provides 2000 lux to each eye. The subjects wore the light visor for 30 min
      in the evening. The subjects were 10 community-residing women over the age of 65
      (mean = 79.4 years; range, 67-87 years). Sleep was recorded in the home for 28
      successive 24-hr periods: 7 days pretreatment, 14 days while using the light
      visor, and 7 days posttreatment. Thus, each subject served as her own control.
      Sleep was recorded using the Home Monitoring System (HMS), a nonintrusive
      procedure which does not require instrumentation of the subject. The subjects
      showed significant changes during and even after the intervention: there was a
      significant decrease in sleep latency over weeks, and a significant increase in
      sleep time and sleep efficiency. The subjects also reported less fatigue during
      treatment. The results suggest that additional light, provided for as little as
      0.5 hr in the evening and at only 2000 lux, increases the amount of nighttime
      sleep and improves the quality of sleep in older women.

PMID- 9547423
TI  - Assessment of self-reward strategies for maintenance of breast self-examination.
AB  - This study examined the relative impact of different self-reward strategies on
      maintenance of breast self-examination (BSE) practice among 1649 women trained to
      do BSE. Training groups were randomized into four conditions: (a) self-reward
      instructions and materials delivered at the end of the BSE training session; (b)
      self-reward suggestions delivered through the mail each month, contingent upon
      the BSE performance; (c) external monetary rewards and self-reward suggestions
      delivered through the mail each month on an intermittent schedule, contingent
      upon BSE practice; and (d) a no-reward control condition. Follow-up assessments
      12 months following training revealed a pattern of evidence in support of the
      benefits of external monetary rewards and self-reward prompts on BSE frequency
      and quality; however, it is likely that the value of that condition lies in the
      external reward component.

PMID- 9547425
TI  - Overall false positive rates in tests for linear trend in tumor incidence in
      animal carcinogenicity studies of new drugs.
AB  - Based on results of simulation and empirical studies conducted within the
      Divisions of Biometrics, Center for Drug Evaluation and Research, Food and Drug
      Administration, and in collaboration with the National Toxicology Program, the
      Center has recently changed the significance levels for testing positive linear
      trend in incidence rate for common and rare tumors, respectively, from 0.01 and
      0.05 to 0.005 and 0.025. The overall false positive rate resulting from the use
      of this new rule in the tests for linear trend in a two-species-two-sex study is
      about 10%, the rate that is judged as the most appropriate in a regulatory
      setting by the Center. This paper describes two of the studies.

PMID- 9547426
TI  - Weighted multiplicity adjustments for animal carcinogenicity tests.
AB  - Sparse data is a difficulty in the analysis of animal carcinogenicity data: it is
      difficult to detect effects when the background tumor rates are low. The widely
      used "Haseman rule" and its variants provide more power to tests with low
      background rates, while maintaining a degree of control over the global false
      positive rate. In this article we explore the use of these rules, finding global
      error rates that are unacceptably high for many animal carcinogenicity studies.
      We provide alternative weighting methods that correct the deficiencies of the
      Haseman rule, and apply them to carcinogenicity data from a pharmaceutical
      company.

PMID- 9547427
TI  - Analysis of homogeneity of treatment effect in adaptive multicenter clinical
      trials.
AB  - In this paper, an exact test for analyzing the homogeneity of treatment effect in
      adaptive multicenter clinical trials is proposed. Extensive simulation studies
      are performed to investigate the large sample behavior of a commonly used test
      statistic for testing homogeneity of treatment effect. When the sample size in
      each center is large relative to the number of centers, the asymptotic null
      distribution of the test statistic is reasonable. On the other hand, when the
      data are relatively sparse, the proposed exact test should be used to incorporate
      the adaptive nature of the design.

PMID- 9547428
TI  - Statistical methodology for screening studies with qualitative/quantitative
      mixtures.
AB  - A statistical method for designing screening studies involving several
      experimental treatments compared to a standard treatment is developed. The
      screening study identifies the most promising experimental treatments, which then
      undergo more rigorous evaluation in a future, larger study. The technique is
      especially relevant for biopharmaceutical research and development in which phase
      II clinical trials are conducted to identify the most promising drug regimens,
      which then move on to phase III of clinical development. It is assumed that the
      underlying distribution of the primary efficacy random variable is a
      qualitative/quantitative mixture. The proposed methodology involves calculating
      the probability of accepting each experimental treatment compared to the standard
      treatment, where the criterion for acceptance is based on the proportion of
      qualitative observations and a measure of their location. The probability of
      acceptance is displayed in two dimensions using operating characteristic contour
      plots. The techniques are illustrated with some practical examples and some
      extensions are indicated.

PMID- 9547430
TI  - Simple methods for determination of the release limits for drug products.
AB  - The potency of a batch of drug product needs to meet a release limits at the time
      of release so that the potency at the end of shelf life remains above the lower
      registration limit (LRL). This article discusses two methods which determine the
      release limits such that the chance to fail LRL at the end of shelf life of the
      product will be controlled under a desirable level. In additional to controlling
      failure rate, a method which determines the release limits such that the expected
      total cost due to rejecting a batch at time zero and at the end of shelf life is
      minimized. All the methods assume a very flexible sampling schedule, and are
      simple to implement. Each method is illustrated in an example.

PMID- 9547429
TI  - An application of methods for clustered binary responses to a cardiovascular
      study with small sample size.
AB  - This paper discusses statistical methods for a cardiovascular study in which each
      of eight animals had a dichotomous outcome observed for each of several
      treatments. There were five treatments in all: shunt, control, two doses of a
      test drug for potentially causing an unfavorable cardiovascular event, and a
      combination of the test drug and a counteracting agent. Exact conditional methods
      were used through LogXact, a statistical software for exact logistic regression
      and an alternative framework for performing a large class of nonparametric tests
      performed by StatXact. The results agreed reasonably with asymptotic methods even
      though the sample size was small.

PMID- 9547431
TI  - Hypothesis testing and confidence interval construction in 2 x 2 tables of
      correlated proportions.
AB  - The 2 x 2 table is an invaluable tool for displaying bivariate binary data. It is
      easy to find examples of correlated binary response in biopharmaceutical
      experiments and clinical research and analysis of these data is a current
      research topic. The most common hypothesis tested for 2 x 2 tables of correlated
      proportions is that of homogeneity of the marginal proportions or, equivalently,
      the hypothesis of table symmetry. The 2 x 2 table of correlated proportions is
      rich with information and we present a survey of some of the analyses relevant
      for these data. Using asymptotic theory, we develop estimators of relevant
      parameters and associated test statistics that are of interest. We discuss
      interval estimation using arguments proposed by Quesenberry and Hurst (1) and
      Goodman (2). These interval estimators do not rely on estimation of the
      covariance matrix and are not necessarily equivalent to those obtained using
      modified chi-square statistics.

PMID- 9547432
TI  - Accommodating negative intracluster correlation with a mixed effects logistic
      model for bivariate binary data.
AB  - We extend the random intercept logistic model to accommodate negative
      intracluster correlations for bivariate binary response data. This approach
      assumes a single random effect per cluster, but entails separate affine
      transformations of this random effect for the two responses of the pair. We show
      this approach works for two data sets and a simulation, whereas other mixed
      effects approaches fail. The two data sets are from a crossover trial and a
      developmental toxicity study of the effects of chemical exposure on malformation
      risk among rat pups. Comparisons are made with the conditional likelihood
      approach and with generalized estimating equations estimation of the population
      averaged logit model. Simulations show the conditional likelihood approach does
      not perform well for moderate to strong negative correlations, as a positive
      intracluster correlation is assumed. The proposed mixed effects approach appears
      to be slightly more conservative than the population-averaged approach with
      respect to coverage of confidence intervals. Nonetheless, the statistical
      literature suggests that mixed effects models provide information in addition to
      that provided by population-averaged models under scientific contexts such as
      crossover trials. Extensions to trivariate and higher-dimensional responses also
      are addressed. However, such extensions require certain constraints on the
      correlation structure.

PMID- 9547433
TI  - Step-down trend tests for identifying the minimum effective dose.
AB  - Many authors, most recently Tamhane, Hochberg, and Dunnett (18), have studied the
      problem of determining the minimum effective dose in dose-response studies. Based
      on past research and on findings from their own extensive simulation study, which
      covered a wide range of balanced normal homoscedastic situations, Tamhane et al.
      recommended a procedure they called SD2L, since it exhibited good performance in
      almost all the situations they studied. This method is a step-down procedure with
      a simple linear contrast-based trend test at each step. In this paper, we
      demonstrate that replacing the linear contrast trend test by Bartholomew's test
      leads to a procedure, SD2B, that consistently outperforms SD2L. In addition to
      the balanced normal homoscedastic framework, the finite sample performance of
      these procedures is also explored under unbalanced and/or heteroscedastic
      conditions. A third procedure, SD2W, which replaces the linear contrast test by
      Welch's test, offers some improvement over SD2B in a few heteroscedastic
      situations. In many cases, the increase in efficiency of SD2B and SD2W over SD2L
      exceeds 10%.

PMID- 9547434
TI  - The analysis of small-sample multivariate data.
AB  - Clinical pharmacology studies typically consist of few subjects per treatment
      group, but with many, possibly highly correlated, measurements taken per subject.
      Permutational methods for testing equality of the multivariate treatment means
      when the number of variables exceeds the number of independent subjects have been
      developed, but are highly computationally intensive. In this paper, a parametric
      test was derived, using Edgeworth expansions, for the case of two groups, and
      compared with competing test statistics proposed by Mercante and Johnson (7),
      Dempster (5), Chung and Fraser (3), Mantel and Valand (6). The proposed test
      compares favorably with the others in terms of type I error rate, as well as
      power, and has the advantages of not requiring computationally intensive
      resources and being easily extendable to more than two groups.

PMID- 9547435
TI  - Unclear points from Bristol's equivalence tests.

PMID- 9547436
TI  - Industry, academia, and postgraduate education.

PMID- 9547437
TI  - The effects of simvastatin on the incidence of heart failure in patients with
      coronary heart disease.
AB  - BACKGROUND: Although treatment of myocardial overload effectively reduces death
      from progression of heart failure, it is not known whether the retardation of
      progressive coronary artery disease obtained with lipid lowering treatment will
      prevent the onset and consequences of heart failure in patients without previous
      symptoms of heart failure. METHODS AND RESULTS: In the Scandinavian Simvastatin
      Survival Study, 4444 patients with coronary heart disease without evidence of
      heart failure were randomized to placebo (n = 2223) or simvastatin 20-40 mg (n =
      2221) and followed for more than 5 years. Among the patients who received
      placebo, 228 (10.3%) were diagnosed with heart failure during follow-up
      evaluation compared with 184 (8.3%) of patients who received simvastatin (P <
      .015). Mortality was 31.9% in the placebo group and 25.5% in the simvastatin
      group among patients who developed heart failure. These compare with 9.2 and
      6.6%, respectively, among non-heart failure patients. There were 45
      hospitalizations because of acute heart failure in the placebo group and 23 in
      the simvastatin group (NS). Patients who developed heart failure were more likely
      to have suffered a recurrent myocardial infarction and have a history of
      diabetes, peripheral artery disease, and hypertension than patients who did not
      develop congestive heart failure. CONCLUSION: Long-term prevention with
      simvastatin reduces the occurrence of heart failure in a cohort of patients with
      coronary heart disease without previous evidence of congestive heart failure.

PMID- 9547438
TI  - Clinical trials for prevention of congestive heart failure: from retrospective
      analysis to prospective hope.

PMID- 9547439
TI  - Ventilatory drive during exercise in congestive heart failure.
AB  - BACKGROUND: Continuous increases in the ventilatory equivalent for carbon dioxide
      (the ratio of minute ventilation to carbon dioxide production, an index of
      ventilatory drive) during exercise in patients with congestive heart failure
      would suggest that factors other than carbon dioxide excessively stimulate
      ventilation during exercise, and may be an important factor in exercise-related
      dyspnea and fatigue in these patients. METHODS AND RESULTS: Eighty-five patients
      with congestive heart failure and 17 normal control subjects underwent symptom
      limited exercise testing with gas-exchange analysis. Patients were divided into
      four functional classes (A-D, Weber's classification) based on peak exercise
      oxygen consumption. In all heart failure patient groups and in control subjects
      the ventilatory equivalent for carbon dioxide decreased (P < .005, class D; P <
      .0001, all other groups) from rest to anaerobic threshold. Three isolated
      patients showed a continuous increase in ventilatory drive during exercise (mean
      peak oxygen consumption 13.7 mL/kg/min). In the lowest functional class (D) the
      ventilatory equivalent for carbon dioxide was greater than in all other groups at
      rest, at anaerobic threshold, and at peak exercise (P < .01). CONCLUSIONS: In all
      heart failure groups and in normal control subjects ventilatory drive, as
      determined by the ventilatory equivalent for carbon dioxide, decreases during
      exercise, Continuous increases in ventilatory drive during exercise are
      infrequently seen, suggesting that factors other than carbon dioxide production
      do not excessively stimulate ventilation in heart failure patients during
      exercise.

PMID- 9547440
TI  - Pulmonary hemodynamics and endothelin levels in pacing-induced heart failure:
      during rest and exercise.
AB  - Elevated plasma levels of endothelin (ET) have been reported to accompany the
      development of heart failure (HF), and therefore, this potent vasoconstrictive
      peptide has been postulated to contribute to the altered pulmonary hemodynamics
      that occur in this disease process. The overall goal of this study was to examine
      more carefully the relationship between ET levels in the pulmonary system and
      pulmonary hemodynamics in the normal and HF states, during both rest and
      exercise. This study used a porcine model of chronic rapid pacing that has been
      shown in previous studies to produce left ventricular dysfunction and
      neurohormonal system activation consistent with the syndrome of HF. Pigs (n = 10)
      were chronically instrumented to measure pulmonary and systemic hemodynamics,
      parenchymal flow, and ET content and to obtain blood samples from the pulmonary
      circuit in the conscious state. Measurements were performed in the normal control
      state and again following the development of pacing-induced HF (240 beats/min per
      21 days), both at rest and during treadmill exercise (3 mph, 15 degrees incline,
      12 minutes). With HF, under ambient resting conditions, a threefold increase in
      pulmonary plasma ET occurred and was accompanied by a fivefold increase in
      pulmonary vascular resistance. During treadmill exercise, pulmonary plasma ET and
      pulmonary vascular resistance remained elevated in the HF group when compared
      with the normal state and were associated with a sixfold decrease in pulmonary
      parenchymal flow. Pulmonary parenchymal ET content was increased with HF when
      compared with values for normal control subjects (8.5 +/- 0.6 vs 5.6 +/- 0.8 fmol
      ET/mg protein, P < .05). Thus, the findings of this study suggest that in this
      model of HF, increased ET within the pulmonary circuit contributed to
      abnormalities in resistive properties and parenchymal flow.

PMID- 9547441
TI  - Nebivolol in the treatment of cardiac failure: a double-blind controlled clinical
      trial.
AB  - BACKGROUND: Nebivolol is a highly cardioselective long-acting beta-blocker with
      vasodilating properties, which acts in part via the endothelial L-arginine/nitric
      oxide pathway. As an antihypertensive drug it is effective in once-daily dosage.
      Nebivolol has previously been shown to improve left ventricular function in
      patients with cardiac impairment. METHODS AND RESULTS: This paper reports a
      double-blind randomized trial comparing, in patients with heart failure, once
      daily nebivolol 2.5 or 5.0 mg (initiated in all at 2.5 mg) with placebo on a
      constant background of digitalis plus diuretic. There was with nebivolol no
      overall deterioration of cardiac function or cardiac symptoms, and especially not
      of exercise capacity, in comparison with placebo. One patient on nebivolol 2.5 mg
      developed hypotension and pulmonary edema, and one patient on nebivolol 5 mg,
      bradycardia. All the remaining patients continued with unchanged diuretic and
      digitalis dosage. Nebivolol was accompanied by a trend toward clinical and
      functional improvement; rather better results were obtained with 2.5 than 5.0 mg.
      CONCLUSIONS: In view of increasing interest in beta-blockade in heart failure,
      nebivolol merits further study in this context. The capacity of nebivolol to
      enhance endothelial nitric oxide production appears potentially attractive.

PMID- 9547442
TI  - Contrasting preload-dependent hemodynamic and neurohumoral effects of isomazole,
      a partial phosphodiesterase inhibitor and calcium sensitizer.
AB  - BACKGROUND: Currently evaluated positive inotropic agents that act predominantly
      through phosphodiesterase III-inhibiting properties, have been disappointing in
      the treatment of heart failure. Lack of efficacy as a result of diminished
      cellular cyclic adenosine monophosphate and vasodilating tolerance and side
      effects are prevalent. In contrast, calcium sensitization is preserved in heart
      failure and agents that combine phosphodiesterase-inhibiting and calcium
      sensitizing properties may be more efficacious. Isomazole is such a novel agent
      with combined properties. This study investigated the acute hemodynamic and
      neurohormonal effects of intravenous isomazole (3 micrograms/kg/min for 30
      minutes). METHODS AND RESULTS: The effects of preexisting preload were evaluated
      in 18 patients with heart failure, New York Heart Association class II/III, and
      elevated (> 15 mmHg, n = 11, group I) and normal; (n = 7, group II) pulmonary
      wedge pressure at baseline. In the overall group, isomazole increased myocardial
      contractility and relaxation and decreased systemic resistance by 20%. Left and
      right filling pressures fell by 35-45%, accompanied by a 69% reduction in cardiac
      atrial natriuretic peptide release. In contrast, levels of arterial
      norepinephrine and renin both increased by 27%. Cardiac output increased in group
      I (23%), but fell in group II (18%), accompanied by a 51% increase in arterial
      norepinephrine. Cardiac atrial natriuretic peptide decreased in group I, but not
      in group II. CONCLUSIONS: Isomazole induced positive inotropic and lusitropic
      effects and arterial vasodilation in all patients. Cardiac pump function improved
      only in group I, accompanied by a reduction in sympathetic activity and renin
      angiotensin and aldosterone levels and a more pronounced decrease in cardiac
      atrial natriuretic peptide release. In contrast, in patients with normal to low
      preload, the further reduction in preload led to a deterioration of pump function
      and increased sympathetic tone.

PMID- 9547443
TI  - Effects of angiotensin-converting enzyme inhibitor on plasma B-type natriuretic
      peptide levels in patients with acute myocardial infarction.
AB  - BACKGROUND: Plasma levels of B-type natriuretic peptide (BNP) are markedly
      increased in patients with heart failure and acute myocardial infarction. The
      changes in plasma BNP levels in the treatment of acute myocardial infarction with
      angiotensin-converting enzyme inhibitors have not been examined well. This study
      was designed to examine the effects of early angiotensin-converting enzyme
      inhibitor therapy on plasma BNP levels in patients with acute myocardial
      infarction. METHODS AND RESULTS: We measured the plasma levels of B-type
      natriuretic peptide over the time course for 2 weeks in 30 patients with acute
      myocardial infarction in whom either imidapril (n = 15) or placebo (n = 15) was
      given at random immediately after admission. Plasma BNP levels increased and
      reached a peak of 192 +/- 28 pg/ML 16 hours after administration; thereafter, the
      levels decreased and then again increased, forming the second peak of 217 +/- 38
      pg/ML on the fifth day (biphasic pattern). On the other hand, plasma BNP levels
      increased and reached a peak level of 190 +/- 22 pg/ML 16 hours after admission
      and then decreased from 2 days after admission until the second week in the
      imidapril group (monophasic pattern). Left ventricular ejection fraction measured
      in the second week was significantly higher in the imidapril group than in the
      control group (62.2 +/- 1.1% vs 51.2 +/- 3.6%, P < .01). CONCLUSION: It is
      concluded that plasma BNP levels followed a monophasic pattern after imidapril
      treatment, whereas a biphasic pattern was followed after placebo, and that plasma
      BNP levels constitute a marker of ventricular dysfunction in the treatment of
      acute myocardial infarction with angiotensin-converting enzyme inhibitors.

PMID- 9547444
TI  - Angiotensin-converting enzyme inhibitors in heart failure: physicians'
      prescribing behavior.
AB  - BACKGROUND: Several studies document an underuse of angiotensin-converting enzyme
      inhibitors (ACEIs) in heart failure (HF) patients, despite their proven efficacy
      and good tolerability. Also, there is some evidence that the doses used in
      clinical practice are far lower than those used in clinical trials. METHODS AND
      RESULTS: To identify patterns of ACEI use in HF patients this study examined data
      collected on admission day regarding demographic, clinical, and medical care
      characteristics of 355 patients hospitalized because of decompensated HF who were
      treated with and without ACEIs. Additionally, measures of in-hospital outcome
      were compared among the two groups. Fifty-eight point six percent of patients
      were receiving ACEIs at admission and 80.6% were treated with ACEIs during
      hospitalization. The average ACEI does was low. No differences were observed in
      age and measures of severity of HF between ACEI-prescribed and nonprescribed
      patients. Patterns that could explain ACEI underuse included female sex, lower
      systolic blood pressure, worse renal function, left ventricular diastolic
      dysfunction, use of alternate drugs (eg, spironolactone), and overall less
      intense medical management. Patterns associated with the use of lower doses of
      ACEIs included older age, higher New York Heart Association functional class, and
      lower systolic blood pressure. In-hospital death rates were significantly higher
      for patients not treated with ACEIs. CONCLUSIONS: This study suggests that many
      patients eligible for ACEI treatment were deprived of the advantages of these
      drugs because of erroneous clinical strategies. Nevertheless, the patterns of
      ACEI use were similar to those reported by other studies. Clinical trials
      conducted to determine the risk/benefit ratio of ACEI use in patients with renal
      dysfunction and the utility of ACEIs in diastolic HF, as well as programs to
      educate care providers on proper use of ACEIs in HF patients, are strongly
      recommended.

PMID- 9547446
TI  - Altered vascular function in early stages of heart failure in hamsters.
AB  - BACKGROUND: Congestive heart failure is a clinical condition associated with
      alterations in the normal balance of neurohumoral agents and factors acting on
      the vascular wall. The etiology of this condition, however, remains largely
      undefined. To help elucidate the pathophysiology of this disease, vascular
      function and angiotensin-converting enzyme activity were evaluated in 2-month-old
      Syrian cardiomyopathic hamsters (SCHs) that had not yet developed heart failure.
      Age-matched normal hamsters were used as control hamsters. METHODS AND RESULTS:
      Vascular function studies included determinations of contractile responses of
      aortic rings to 0.1 microM angiotensin II and 0.1 microM norepinephrine. In
      addition, endothelial function was evaluated by the vasorelaxant action of
      acetylcholine on norepinephrine-precontracted aortic rings. The results indicate
      that the pressor effect of angiotensin II (0.1 microM) was 35% greater in aortic
      rings from SCRs than that observed in control animals. This effect is specific
      for angiotensin II because the contraction induced by NE (0.1 microM) was similar
      in both of these strains. Angiotensin-converting enzyme activity was three-fold
      higher in aorta homogenates from SCHs but normal in plasma and heart tissue when
      compared with control hamsters. Aortic ring preparations from SCHs also exhibited
      endothelial dysfunction because the maximal relaxation elicited by 10 microM
      acetylcholine was reduced 53%. Concentration-response curves with acetylcholine
      yielded EC50 values that were threefold lower in SCHs (97.2 +/- 0.1 nM) than in
      control animals (286 +/- 7 nM). Indomethacin (1 microM) increased the
      vasorelaxant effect of acetylcholine 28% in SCHs and shifted to the left the
      concentration-response curve of this agonist, suggesting an increased relaxation
      with the cyclooxygenase inhibitor. No effect of indomethacin on acetylcholine
      induced relaxation was observed in control animals. Sodium nitroprusside induced
      similar relaxations in both control animals and SCHs, suggesting that the
      vascular smooth muscle response is normal in SCR. CONCLUSIONS: Altogether these
      results point to a state of enhanced vascular contractility in young SCHs that
      could predispose these animals to develop heart failure, the enhanced vascular
      contractility could result from increased activity of the local renin-angiotensin
      system, augmented vascular response to angiotensin II, reduced nitric oxide
      synthesis, and enhanced production of prostaglandins.

PMID- 9547445
TI  - Up-regulated expression of angiotensin II type 1 receptor gene in human
      pathologic hearts.
AB  - BACKGROUND: An accumulation of evidence suggests that the local renin-angiotensin
      system plays a role in the development of cardiac hypertrophy in vivo; however,
      it remains unknown how the expression of angiotensin II type 1 receptor (AT1),
      which mediates most of the cardiovascular effects of angiotensin II, is regulated
      in the left ventricles of human pathologic hearts. METHODS AND RESULTS:
      Expression of AT1 gene in the left ventricle wall of 14 autopsied human hearts
      was examined by reverse transcription polymerase chain reaction. The levels of
      AT1 messenger RNA relative to those of beta-actin messenger RNA in the left
      ventricle wall were increased 3.8-fold in the hearts with dilated cardiomyopathy
      (n = 4, P < .05) and 6.2-fold in the noninfarcted areas of hearts with old
      myocardial infarction (n = 4, P < .05), compared with the control hearts without
      any cardiac disease (n = 6). The increases in the relative AT1 messenger RNA
      level showed a positive correlation with myocyte diameter in the adjacent tissue
      (r = .927, P < .001 for dilated cardiomyopathy and r = .934, P < .005 for old
      myocardial infarctions) and with the extent of fibrosis (r = .880, P < .005 for
      dilated cardiomyopathy and r = .690, P < .05 for old myocardial infarction).
      CONCLUSIONS: Expression of AT1 in these human pathologic hearts was associated
      with myocardial cell hypertrophy and extent of fibrosis, a finding that further
      emphasizes the importance of the local renin-angiotensin system in the remodeling
      of human hearts with dilated cardiomyopathy and old myocardial infarction.

PMID- 9547447
TI  - Evolving concepts of heart failure: cooling furnace, malfunctioning pump,
      enlarging muscle--Part I.
AB  - Understanding of the causes of dyspnea and anasarca, the cardinal features of
      heart failure, has changed dramatically since Greco-Roman times, when sputum and
      pleural effusions were thought to originate in the brain, and the heart was
      believed to heat and distribute the vital spirit. It was not until the
      seventeenth century, when Harvey demonstrated that the heart was a pump and
      autopsy descriptions revealed valve abnormalities that interfered with the
      circulation, that it became possible to identify the role of heart disease in
      causing shortness of breath and edema. Morgagni's recognition, toward the end of
      the eighteenth century, that overload caused the heart to enlarge was followed
      less than 50 years later by Corvisart's distinction between hypertrophy and
      dilation. Differences in the architecture of failing hearts focused attention of
      nineteenth-century clinical scientists on the myocardial response to overload,
      and by the end of this century overload-induced hypertrophy was recognized not
      only to have immediate adaptive effects, but also to cause progressive
      degeneration of the heart muscle. This focus on the failing myocardium ended in
      the early years of the twentieth century, when new discoveries in hemodynamic
      physiology shifted attention to pressure and flow abnormalities caused by the
      then prevalent rheumatic valvular heart disease. During the past decade, new
      emphasis on prognosis, along with realization that drugs intended to correct
      hemodynamic abnormalities often had adverse effects on survival, has led to a
      reexamination of the biology of the failing heart. As a result, the focus in
      heart failure research has returned to the myocardium. This article reviews some
      of the misconceptions and errors of early physicians, who, while often careful
      and intelligent observers, lacked the means to explain and treat heart failure.
      It is hoped an appreciation of the evolving concepts of heart failure will help
      the reader meet today's challenge of incorporating new information from molecular
      biology that holds the key to further progress in understanding the causes and
      therapy of this syndrome.

PMID- 9547448
TI  - On the horizon: minimally invasive cardiac surgery.
AB  - The landscape of cardiac surgery is changing. Advances in endoscopic and other
      instrumentation procedures such as port access, video instrumentation, and
      computer-assisted technology are opening new vistas for cardiac surgery. On the
      immediate horizon is minimally invasive cardiac surgery, also known as keyhole
      surgery. Imagine a patient not needing a median sternotomy incision or
      cardiopulmonary bypass. This new type of cardiac surgery is currently being
      explored at some cardiac surgical centers internationally. This article explores
      the current state-of-the-art related to minimally invasive direct coronary artery
      bypass surgery. The operative procedure, implications for perioperative nursing
      care, likely future technologies, and the research literature on outcomes are
      also discussed.

PMID- 9547449
TI  - Transmyocardial laser revascularization.
AB  - Transmyocardial laser revascularization is a new treatment modality for patients
      with chronic angina that is refractory to traditional management. A laser is used
      to create full-thickness channels through areas of ischemic myocardium.
      Transmyocardial laser revascularization is performed in an effort to improve
      myocardial oxygenation, eliminate or reduce angina, and improve functional
      status. Transmyocardial laser revascularization currently is undergoing clinical
      trials. Early results have demonstrated significant reduction in anginal
      symptoms. Long-term efficacy of transmyocardial laser revascularization remains
      to be determined.

PMID- 9547450
TI  - Advances in myocardial protection.
AB  - The success of cardiac surgery is due in large part to the myocardial protection
      techniques employed to maintain cardiac viability during the period of induced
      ischemic arrest. As the number of older, high-risk cardiac surgical patients
      increases, advances in myocardial protection have become necessary to achieve a
      quiet, bloodless operative field without the production of irreversible
      intraoperative myocardial damage. Current efforts to provide optimal myocardial
      protection have focused on the effects of cardioplegic perfusate temperature,
      distribution of cardioplegia flow, and components of the arresting solution.
      Minimally invasive techniques have expanded surgical options and have led to the
      development of new methods to protect the myocardium.

PMID- 9547451
TI  - Managing pain after coronary artery bypass surgery.
AB  - Nurses are responsible for assessing patients' pain and intervening with
      modalities such as opioids. However, after coronary artery bypass surgery,
      patients experience moderate to severe pain and receive inadequate analgesia.
      These practices are problematic as unrelieved acute pain is harmful and may
      result in negative consequences that influence recovery. Consistent with the
      subjectivity and multidimensionality of pain, as described in Gate Control
      Theory, patients need to be involved as participants in their care where
      possible. Pain policies and education programs need to reflect current
      professional guidelines and be proactive in addressing staff and patient gaps in
      pain knowledge and misbeliefs.

PMID- 9547452
TI  - Pharmacology.
AB  - Inadequate pain relief has been identified as a common problem after coronary
      artery bypass surgery, Understanding the pharmacology of analgesics commonly used
      after cardiovascular surgery is a fundamental part of effective pain management.
      The pharmacologic properties for two analgesic drug classes, opioid and
      nonopioid, are reviewed. Major drugs in each class are discussed in terms of
      their pharmacodynamic and pharmacokinetic properties.

PMID- 9547453
TI  - Management of postoperative atrial fibrillation.
AB  - Atrial fibrillation is a common complication of heart surgery. Consequences for
      the patient who develops this dysrhythmia are many. It prolongs hospitalization,
      may induce hemodynamic compromise, and carries the risks of thromboembolism and
      stroke. Ongoing research for the past 30 years has identified several potential
      etiologies; therefore, management must be highly individualized. This article
      reviews current and past research on postoperative atrial fibrillation with a
      focus on individualized prevention and treatment of this problematic heart
      surgery complication.

PMID- 9547455
TI  - A comprehensive approach to facilitating the recovery of cardiac surgery
      patients.
AB  - This article describes the cardiac surgery program at Baystate Medical Center. It
      emphasizes the importance of planning for the discharge process, early
      extubation, and structured activity guidelines and their effect on patient
      outcomes. The unique roles of the staff nurse, mid-level practitioner, and the
      clinical resource coordinator in facilitating the case management process are
      addressed.

PMID- 9547454
TI  - Dysrhythmia update: The effect of intermittent heart block on the central venous
      pressure trace.
AB  - A 75-year-old man developed heart block with intermittent conduction following
      mitral valve replacement. A simultaneously recorded central venous pressure (CVP)
      trace revealed evidence of the normal sequence of atrial and ventricular
      contraction, as well as episodes of ventricular contraction that preceded atrial
      contraction and episodes of simultaneous atrial and ventricular contraction. The
      dysrhythmia and CVP trace are analyzed and clinical implications relevant to this
      case history are discussed.

PMID- 9547456
TI  - The Middle/Upper Paleolithic interface and the relationship of Neanderthals and
      early modern humans in the Hrvatsko Zagorje, Croatia.
AB  - This paper presents the first detailed analysis of the artefacts from the
      Mousterian level G3 at Vindija Cave and a revision of the artefact analysis for
      the early Upper Paleolithic levels (j, i) at Velika Pecina, both in Croatia.
      Combined with an assessment of the artefacts from the crucial G1 level at
      Vindija, results of these analyses are used to argue that the combination of
      Middle and Upper Paleolithic elements in the upper G complex at Vindija is not
      necessarily the result of geological mixing but may well represent a natural
      cultural assemblage. Some Upper Paleolithic elements are possibly derived from
      the local Mousterian, while others result from extraneous cultural influences
      into this region. Interestingly, currently available radiocarbon dates indicate
      that Neanderthals (Vindija level G1) and early modern humans (Velika Pecina) were
      penecontemporaneous in this region at ca. 33 ka, or perhaps somewhat earlier if
      the radiocarbon dates are taken as minimum age estimates. Therefore some Upper
      Paleolithic tools associated with the Vindija G1 Neanderthals, such as bone
      points, may result from imitation of or trade with early modern people. While
      there is external influence on the development of the early Upper Paleolithic in
      this region, it exhibits a unique character which does not conform to that of
      classic Western or Central European Aurignacian.

PMID- 9547457
TI  - Comparative morphometric study of the australopithecine vertebral series Stw
      H8/H41.
AB  - Lower spinal structure correlates well with positional behavior among mammals.
      Nonetheless, the functional morphology of the axial post-crania of
      australopithecines has received less attention than their appendicular skeletons.
      This paper presents a detailed description and comparative morphometric analysis
      of the australopithecine thoracolumbar vertebral series Stw-H8/H41, and examines
      spinal mechanics in early hominids. Stw-H8/H41 is an important specimen, as the
      australopithecine vertebral sample is small, and vertebral series are more useful
      than isolated elements for the interpretation of spinal function. Results of the
      study support the interpretation that australopithecine species are highly
      sexually dimorphic. The study also reveals a considerable amount of morphometric
      variation other than size among australopithecine vertebrae, though the sample is
      too small and incomplete to ascertain whether this indicates significant
      interspecific differences in spinal function. Most importantly, structural and
      metric observations confirm that the morphology of the lower spine in
      australopithecines has no modern analogue in its entirety. Aspects of
      zygapophyseal structure, numerical composition of the lumbar region, and centrum
      wedging suggest that the australopithecine vertebral column was adapted to human
      like intrinsic lumbar lordosis and stable balance of the trunk over the pelvis in
      sustained bipedal locomotion. However, relative centrum size in
      australopithecines indicates that either they had a different mechanism for
      channeling vertical forces through the vertebral column than humans, or differed
      behaviorally from humans in ways that produced smaller increments of compression
      across their centra. These findings have important implications for hypotheses of
      australopithecine positional behavior, and demonstrate that larger samples and
      more complete vertebral series are needed to improve our understanding of
      australopithecine spinal function.

PMID- 9547459
TI  - A metrical study of the WLH-50 calvaria.

PMID- 9547458
TI  - Mortality analysis of Pleistocene bears and its paleoanthropological relevance.
AB  - Bear bones and Paleolithic stone artefacts often co-occur in Pleistocene cave
      deposits of Eurasia, raising the question of how these associations come about
      and the need for effective methods with which to obtain a clear answer. Building
      upon knowledge of modern bears, I present a method for testing two competing
      hypotheses about the causes of bear mortality in hibernation contexts. The first
      hypothesis proposes that age-dependent deaths resulted from non-violent causes
      (principally starvation), implying that bears' presence in a cave was not linked
      in time to human activities there. The second hypothesis proposes that random
      bear deaths in caves resulted from hunting by humans or other large predators,
      implying a temporal link between them; the expectation of a nonselective age
      pattern in this circumstance arises from the fact that the individual characters
      of hibernating bears are hidden from predators. Three elements of the method and
      its development are presented: (1) a brief review of the biological bases of
      hibernation-related mortality in modern Ursus, its paleontological consequences,
      and test expectations drawn therefrom; (2) a detailed, illustrated technique for
      age-scoring isolated bear cheek teeth based on tooth eruption-wear sequences,
      developed primarily for cave and brown bears; and, (3) a simple, accurate way to
      evaluate real cases in terms of contrasting mortality models. The final step is
      demonstrated by application to a Middle Pleistocene cave bear assemblage (Ursus
      deningeri) from Yarimburgaz Cave in Turkey, a large collection found in general
      stratigraphic association with Paleolithic artefacts. The advantages of the
      method include its ability to (a) handle small samples, (b) use isolated tooth
      specimens, and (c) evaluate cases simultaneously in terms of idealized age
      structure models and the variation that normally is associated with each under
      natural conditions. While the more obvious benefit of bear mortality analysis may
      be to research on ancient bear demography, the principles and procedures offered
      here are equally pertinent to archaeological studies of carnivore-mediated
      formation processes in cave sites. As is generally true in taphonomic research,
      however, bear mortality patterns are most effective when used in combination with
      independent lines of evidence to address questions about assemblage formation.

PMID- 9547460
TI  - The clinician-scientist in neuropsychiatry: a position statement from the
      Committee on Research of the American Neuropsychiatric Association.
AB  - Neuropsychiatric research seeks to improve the lives of patients with brain-based
      behavioral disturbances. There has been dramatic progress in diagnosis and
      treatment of neuropsychiatric disorders, and progress in neuroscience and
      biotechnology promises further success. Paradoxically, recent trends threaten to
      erode this progress. In this environment, neuropsychiatric clinician-scientists
      must advocate for the importance of research. This position statement defines
      neuropsychiatric research, describes current challenges to the neuropsychiatric
      clinician-scientist, summarizes research opportunities, describes how future
      neuropsychiatric clinician-investigators should be trained, and makes
      recommendations for promoting neuropsychiatric research.

PMID- 9547461
TI  - Neuropsychiatric aspects of the adult variant of Tay-Sachs disease.
AB  - Tay-Sachs disease (a GM2 gangliosidosis) is an inherited neuronal storage disease
      that can affect individuals across the age spectrum. Psychosis is reported in 30%
      to 50% of adult-onset patients, and many are misdiagnosed with schizophrenia.
      Mood disorders are present in more than 25% and cognitive impairment in more than
      20%. Treatment of psychosis with neuroleptics may not have a favorable
      risk/benefit ratio, but treatment with benzodiazepines or electroconvulsive
      therapy may be efficacious. Metabolic diseases such as gangliosidosis are
      probably under-recognized as causes of neuropsychiatric illness. Increased
      awareness of these disorders will lead to accurate diagnosis, appropriate
      treatment selection, and genetic counseling.

PMID- 9547462
TI  - The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory
      depressed patients.
AB  - Rapid-rate transcranial magnetic stimulation (rTMS) allows for the noninvasive
      examination of the cerebral cortex. Recent studies have begun to investigate
      whether rTMS may be therapeutic for the treatment of depression. In the present
      study, the authors report on the safety and efficacy of rTMS in treating 50
      patients with refractory depression. Overall, there were 21 responders (42%).
      Interestingly, 56% of the young patients responded, but only 23% of the elderly
      patients responded to rTMS. Overall, rTMS was well tolerated in all patients.
      Specifically, no patient developed a new onset of seizures during rTMS. The
      authors discuss the extant literature on rTMS for the treatment of depression
      along with future areas of research.

PMID- 9547463
TI  - Functional impairment associated with acute poststroke depression: the Stroke
      Data Bank Study.
AB  - To examine the independent association of depression following acute stroke with
      impairment in activities of daily living (ADL), the authors conducted a cross
      sectional analysis of stroke patients enrolled in the Stroke Data Bank (U.S.A.)
      who had completed the Center for Epidemiological Studies Depression Scale (CES
      D). Scores on the Barthel Index, a measure of ADL, were compared between
      depressed (CES-D > or = 16) and nondepressed patients (CES-D < or = 15) at 7-10
      days after stroke. Of the 626 who completed CES-D, 160 were depressed. Depressed
      stroke patients evidenced greater impairment in ADL than nondepressed patients,
      independently of all other factors that influenced poststroke physical
      disabilities. CES-D scores were negatively correlated with Barthel scores in the
      entire stroke population. Neurological factors, greater age, poor prestroke
      physical activity, and prestroke disturbances in sexual functioning were also
      independently associated with limitations in functional status of stroke
      patients.

PMID- 9547464
TI  - Effects of anxiety disorder on impairment and recovery from stroke.
AB  - The effect of anxiety disorder on recovery from impairment following stroke was
      examined in 142 patients with acute stroke who had follow-up evaluations. Anxiety
      disorder significantly interacted with depression to influence the severity and
      course of depression, outcome of activities of daily living, and social
      functioning. Anxiety disorder, however, did not affect cognitive impairment,
      which was influenced only by major depression. These data suggest that the
      existence of anxiety disorders plays an important role in the prognosis of
      patients with poststroke depression. These data also suggest that depression and
      anxiety disorder may have different mechanisms.

PMID- 9547465
TI  - Gender differences in poststroke depression.
AB  - In stroke and other medical illnesses, secondary depression may be associated
      with different factors in women than in men. The authors examined 301 consecutive
      admissions for acute treatment of cerebrovascular accident for gender differences
      in depression, psychosocial factors, physical impairment, and lesion location.
      Women were twice as frequently diagnosed with major depression as men. Women with
      major depression had a greater frequency of left hemisphere lesions than men. In
      men, major depression was associated with greater impairment in activities of
      daily living, and greater severity of depression was associated with greater
      impairment in daily activities and social functioning. In women, greater severity
      of depression was associated with prior diagnosis of psychiatric disorder and
      cognitive impairment. These findings suggest a different nature of poststroke
      depression in men and women and may have implications for its treatment.

PMID- 9547466
TI  - Chronological association between increases in drug abuse and psychosis in
      Connecticut state hospitals.
AB  - Disagreement remains as to whether drug use can result in an autonomous psychotic
      disorder. If drug use can create new psychosis cases, an increase in the number
      of psychosis patients ought to be observable following periods of increased drug
      use by the general population. First admissions data for the categories of drug
      abuse and schizophrenia/paranoid disorders from all Connecticut state hospitals
      from 1965 to 1983 were examined to determine the prevalence of psychotic
      disorders before, during, and after a period of increased drug use by the general
      population. Affective disorders first admissions were examined for comparison. A
      rapid increase in new schizophrenia admissions coincided with a peak period for
      drug-related admissions. The data suggest that increased drug use of the late
      1960s may have contributed to the increase noted 3 to 5 years later in first
      admissions of patients diagnosed with psychotic disorders.

PMID- 9547467
TI  - Differential neuropsychiatric symptom responses to tacrine in Alzheimer's
      disease: relationship to dementia severity.
AB  - Neuropsychiatric symptom responses to tacrine were investigated in an open-label
      study of Alzheimer's outpatients. Forty subjects were stratified into three
      groups (Mild, Moderate, and Severe) based on Mini-Mental State Examination
      scores. A significant reduction in total Neuropsychiatric Inventory score across
      all subjects was principally attributable to changes in the Moderate group.
      Apathy and disinhibition symptoms were significantly reduced overall. Whereas
      other symptoms showed differential responses in Mild and Severe subjects, all
      symptoms improved in Moderate subjects. These findings suggest that disease
      severity may significantly influence neuropsychiatric symptom responses to
      tacrine. Putative mechanisms underlying the observed pattern of responses are
      explored.

PMID- 9547468
TI  - Olfactory dysfunction discriminates Alzheimer's dementia from major depression.
AB  - This study tested the hypothesis that olfactory dysfunction could discriminate
      between groups of patients with Alzheimer's disease and major depression. Forty
      patients meeting DSM-IV criteria for Alzheimer's disease and for major depression
      (20 per group) underwent assessment with the Pocket Smell Test (PST), a three
      item screening measure of cranial nerve I function. A PST score of < or = 1 (1 or
      0 correct) discriminated between the groups with a hit rate of 90% (sensitivity =
      80%, specificity = 100%). Olfactory assessment may be a useful adjunctive
      screening measure in differentiating Alzheimer's disease from depression in
      elderly patients.

PMID- 9547469
TI  - Determinants of spontaneous extrapyramidal symptoms in elderly psychiatric
      inpatients diagnosed with Alzheimer's disease, major depressive disorder, or
      psychotic disorders.
AB  - Extrapyramidal symptoms (EPS) occur more frequently in dementia of the
      Alzheimer's type (DAT) than in normal aging. Other late-life mental disorders,
      however, have also been associated with EPS. To examine whether EPS are increased
      in DAT patients relative to neuropsychiatric control subjects, the authors
      compared EPS in 127 neuroleptic-free elderly patients diagnosed with either DAT,
      major depressive disorder (MDD), or a psychotic disorder (SCHIZ/DELUS). They also
      examined whether depressive or psychotic symptoms were associated with EPS
      independently of diagnosis. Severity of parkinsonian rigidity was found to be
      independently associated with DAT. Rank order of rigidity was DAT > MDD >
      SCHIZ/DELUS. Bradykinesia, although not associated with diagnostic group, was
      positively correlated with withdrawn depression. These findings suggest that
      rigidity is associated with DAT independently of any concurrent psychotic or
      depressive process, whereas bradykinesia does not appear to be specific to DAT
      among late-life neuropsychiatric illnesses.

PMID- 9547471
TI  - The motor agitation and retardation scale: a scale for the assessment of motor
      abnormalities in depressed patients.
AB  - Increasing recognition of the neurologic aspects of depressive disorder has
      aroused new interest in the potential neuropathologic significance of
      "psychomotor" symptoms in depression. Psychomotor symptoms have yet to be clearly
      defined, however. The Motor Agitation and Retardation Scale (MARS) was developed
      to provide a comprehensive and nonredundant measure of the motor abnormalities
      associated with agitation and retardation in depression. Forty-one depressed in
      patients and 20 normal control subjects were assessed. In this sample, the MARS
      provided a reliable and valid scale for the clinical assessment of 19 abnormal
      motor behaviors associated with agitation and retardation in depression. The MARS
      may be useful for investigation of the pathophysiologic significance of various
      manifestations of motor abnormalities in depression and, as part of a larger
      battery, for the investigation of the relative contribution of motor
      abnormalities to psychomotor impairment in depression.

PMID- 9547470
TI  - Blood-brain barrier integrity in Alzheimer's disease patients and elderly control
      subjects.
AB  - A defective blood-brain barrier (BBB) has been postulated to be present in
      Alzheimer's disease (AD), which would allow circulating beta-amyloid peptide to
      enter the brain. The authors tested this hypothesis by studying BBB function in
      14 individuals with probable AD and 9 elderly control subjects. A computed
      tomographic method was used to measure blood-to-brain transport (K1), tissue-to
      blood efflux (k2), tissue plasma space (Vp), and tissue extracellular space (Ve)
      of meglumine iothalamate. Repeated-measures analysis of variance indicated no
      significant differences between the groups for any of the measures. The authors
      conclude that there is no generalized abnormality of the blood-brain barrier in
      AD.

PMID- 9547472
TI  - Use of clozapine in 10 mentally retarded adults.
AB  - The cost, side effect profile, and required weekly blood draws associated with
      clozapine may dissuade some clinicians from prescribing this atypical neuroleptic
      to mentally retarded patients. All publications on clozapine use in mentally
      retarded patients are reviewed and the treatment of 10 such patients is
      described, bringing the total number of published cases to 84. Clozapine is
      efficacious and well tolerated in this population and should be considered for
      those patients with psychosis or bipolar illness who are intolerant of or
      unresponsive to other agents.

PMID- 9547473
TI  - Is olfactory reference syndrome an obsessive-compulsive spectrum disorder?: two
      cases and a discussion.
AB  - A number of disorders characterized by intrusive repetitive symptoms and varying
      degrees of insight may overlap phenomenologically and neurobiologically with
      obsessive-compulsive disorder (OCD). There is a question as to whether olfactory
      reference syndrome, a disorder characterized by persistent preoccupations about
      body odor accompanied by shame and embarrassment, is also an OCD spectrum
      disorder. Two cases of olfactory reference syndrome, with accompanying
      phenomenological and neurobiological data, are presented in order to discuss the
      possible overlap with OCD. A number of phenomenological and neurobiological
      features in these patients were at least partially reminiscent of OCD. In
      particular, despite having poor insight, both patients demonstrated significant
      improvement upon treatment with a serotonin reuptake inhibitor.

PMID- 9547474
TI  - Prevalence of Alzheimer's disease and apolipoprotein E allele frequencies in the
      Old Order Amish.
AB  - The authors examined the prevalence of Alzheimer's disease and apolipoprotein E
      allele frequencies in the Old Order Amish. A lower frequency of dementia in the
      Amish does not appear to be due to a reduced E4 frequency.

PMID- 9547475
TI  - Does stroke cause depression?

PMID- 9547476
TI  - Risperidone for the treatment of delusional disorder due to HIV disease.

PMID- 9547477
TI  - When fluvoxamine treats only depression and clomipramine treats only obsessive
      compulsive disorder--combine them?

PMID- 9547478
TI  - Buspirone and brain injury.

PMID- 9547479
TI  - Affect and the limbic system: some hard problems.

PMID- 9547480
TI  - Obsessive-compulsive disorder, Tourette's syndrome, and basal ganglia pathology
      on MRI.

PMID- 9547481
TI  - Palicoprolalia: an unusual variant of palilalia in Gilles de la Tourette's
      syndrome.

PMID- 9547482
TI  - Greatest suicide success rate found in depressed elderly.

PMID- 9547483
TI  - The impact of child sexual abuse on addiction severity: an analysis of trauma
      processing.
AB  - The Information of Processing Trauma Model provides a framework for understanding
      the dynamics and responses of childhood sexual abuse. Chemical dependency plays a
      role in both the cause and effect of childhood sexual abuse. Survivors of
      childhood sexual abuse with chemical dependency require treatment of both
      disorders. This treatment should emphasize the key role of the encapsulation
      phase in symptom formation and recovery.

PMID- 9547485
TI  - Preparing feminist facilitators. Assisting abused women in transitional or
      support-group settings.
AB  - This article has reviewed one approach to the preparation of support group
      facilitators to enable them to better meet the needs of abused women. Those women
      may still be in abusive relationships or they may have left one; they may be
      unsure whether they are abused; or they may be seeking practical suggestions
      about ways to tackle a particular problem. Whatever their specific situations,
      they can benefit from a supportive, accepting, and safe environment in which to
      explore their options.

PMID- 9547484
TI  - Implementation of groups for creative expression on a psychiatric inpatient unit.
AB  - Patients benefited from creativity group participation through expression of both
      positive and negative feelings, group acceptance, and acceptance of self in a non
      competitive activity. Psychiatric nurses can lead creativity groups with a focus
      on creative expression, rather than psychotherapy. No specific training in the
      arts is required for these simple creative formats. It was found from using a
      variety of creative formats that, overall, patients received group projects
      better than individual projects done in a group setting.

PMID- 9547486
TI  - Adolescents from families of divorce: vulnerability to physiological and
      psychological disturbances.
AB  - Multiple factors contribute to the vulnerability of adolescents to physiological
      and psychological disturbances following parental divorce. These include father
      absence, interparental conflict, economic distress, multiple life stressors,
      parent adjustment, and short-term crisis. Clinical and societal problems
      manifested in these vulnerable adolescents are discussed. Systems theory is used
      to explain this vulnerability of adolescents and to identify appropriate
      interventions and policies to promote health in this population. Policies
      recommended include required divorce mediation, early referrals for family and
      sibling therapy, and school programs to identify and support those most
      vulnerable.

PMID- 9547487
TI  - Classical conditioning using vestibular reflexes.
AB  - Adaptation of the vestibulo-ocular reflex (VOR) is one of the principal models
      for studying motor learning in the mammalian CNS. However, there has been no
      previous comprehensive attempt to understand the behavioral characteristics of
      VOR adaptation in terms of traditional psychological learning theory. To
      accomplish this objective, the effectiveness of vestibular-evoked responses in
      serving as the conditioned or unconditioned stimulus in classical conditioning
      paradigms is first reviewed. Then, the various procedures for eliciting VOR
      adaptation are reviewed from the perspective of their similarity to standard
      classical conditioning protocols. A systematic analysis of Western and Russian
      literature yielded a relatively small number of studies that explicitly used
      vestibular reflexes in classical conditioning paradigms, and they report a wide
      range in success. Potential explanations for these diverse findings are
      discussed. A comprehensive categorization of the behavioral parallels between VOR
      adaptation and classical conditioning is then presented. Viewing VOR adaptation
      as a form of classical conditioning is a useful heuristic device and leads
      directly to the description of further behavioral experiments that could throw
      additional light on general mechanisms for inducing neural plasticity. Such an
      exercise is of benefit in order to further understand the common framework which
      might exist between VOR adaptation and other models of motor learning (for
      example, rabbit eye blink conditioning).

PMID- 9547488
TI  - Immersed false vertical room. A new motion sickness model.
AB  - We evaluated a new model of motion sickness--an enclosure decorated with visual
      cues to upright which was immersed either inverted or "front"-wall down, in
      Johnson Space Center's Weightless Environment Training Facility (WETF) pool. This
      "WETF False Vertical Room" (WFVR) was tested with 19 male and 3 female SCUBA
      diver subjects, aged 23 to 57, who alternately set clocks mounted near the room's
      8 corners and made exaggerated pitch head movements. We found that (1) the WFVR
      test runs produced motion sickness symptoms in 56% and 36% of subjects in the
      room-inverted and room-front-down positions, respectively. (2) Pitch head
      movements were the most provocative acts, followed closely by setting the clocks-
      particularly when a clock face filled the visual field. (3) When measured with a
      self-ranking questionnaire, terrestrial motion sickness susceptibility correlated
      strongly (P < 0.005) with WFVR sickness susceptibility. (4) Standing instability,
      measured with a modified Fregly-Graybiel floor battery, also correlated strongly
      (P < 0.005) with WFVR sickness susceptibility. This result may reflect a
      relationship between visual dominance and WFVR sickness. (5) A control study
      demonstrated that the inverted and front-down positions produced WFVR sickness,
      but the upright position did not, and that adaptation may have occurred in some
      subjects with repeated exposure. The WFVR could become a useful terrestrial model
      of space motion sickness (SMS) because it duplicates the nature of the gravity
      dependent sensory conflicts created by microgravity (visual and otolith inputs
      conflict while somatosensory gravity cues are minimized), and it also duplicates
      the nature of the provocative stimulus (sensory environment "rule change" versus
      application of motion to passive subject) more closely than any other proposed
      terrestrial SMS model. Also, unlike any other proposed terrestrial SMS model, the
      WFVR incorporates whole-body movement in all three spatial dimensions. However,
      the WFVR's sensory environment differs from that created by spaceflight in
      several respects, including the presence of frictional drag on limb movement,
      magnification at the face-mask-water interface, greater otolith conflict, exhaled
      bubbles, and the presence of some gravity-dependent somatosensory inputs.

PMID- 9547489
TI  - Further evidence for gender differences in circularvection.
AB  - This paper reports further evidence that gender is a significant factor in the
      experience of circularvection (CV), the illusion of self-rotation. Using
      optokinetic drum velocities between 24 degrees and 92 degrees/s, latency to
      experience Stage 2 or Stage 3 CV was measured. Males exhibited significantly
      longer CV latencies than females (P < 0.0001), although the difference was
      greater for Stage 3 CV than for Stage 2 CV. This result suggests that the
      potential influence of gender must be carefully controlled in visual-vestibular
      interaction experiments.

PMID- 9547490
TI  - Cogan's Syndrome. High resolution MRI indicators of activity.
AB  - In the chronic-relapsing form of Cogan's syndrome, it can be difficult to
      evaluate the activity of the disease. In contrast to the initial stage, routine
      diagnostic techniques sometimes fail to indicate progression in the chronic
      stage. To determine whether high-resolution magnetic resonance imaging (HR-MRI)
      can be used to differentiate between active and inactive stages, we examined
      three patients with Cogan's syndrome (one during an acute relapse, two with
      chronic audiovestibular deficits), all of whom had antibodies to inner ear tissue
      (cochlea, vestibular labyrinth). Unenhanced T1-, T2, gadolinium-enhanced T1
      weighted, and three-dimensional constructive interference in steady stage (CISS)
      images were used. Abnormal MRI signals of the inner ear were related to the
      activity of the disease. The patient studied during an acute exacerbation showed
      abnormal MRI signals in the vestibule, semicircular canals, vestibular nerve, and
      cochlea, which disappeared after the relapse. These abnormalities included high
      signal in the membranous labyrinth, the vestibule, and cochlea, with enhancement
      on T1-weighted images, indicating gadolinium leakage through the abnormal
      labyrinthine membrane into the perilymphatic spaces. In contrast, the other two
      patients with chronic audiovestibular deficits but no clinical signs of an acute
      relapse, had narrowing or occlusion of semicircular canals of the cochlea on the
      3D-CISS images, but no high signal lesions (T1) and no enhancement. We conclude
      that sequential gadolinium-enhanced MRI can identify the active stage of Cogan's
      syndrome. The combination of HR-MRI and antibodies to inner ear antigens are
      helpful in the diagnosis of acute, sequential, bilateral audiovestibular
      impairment of autoimmune origin.

PMID- 9547491
TI  - Direct influence of temperature on the semicircular canal receptor.
AB  - Effect of thermal stimulus on the vestibular receptor was studied using the
      isolated frog semicircular canal. The posterior (PSC) and lateral semicircular
      canals (LSC) were placed in the horizontal plane in frog Ringer's solution. The
      ampullary nerve was sucked into a glass suction electrode to record compound
      potentials. The steel thermal probe was positioned next to the ampullary surface
      to give thermal stimuli. When the PSC ampulla was cooled, the spontaneous
      discharge markedly increased. When the PSC ampulla was warmed, the discharge
      decreased. When the LSC ampulla was cooled, the discharge increased in the same
      manner as in the PSC. Also, warming of the LSC decreased the discharge in the
      same manner as in the PSC. The cupula was removed from the crista in order to
      eliminate the effect of volume change of the endolymph. The results were
      comparable to those with intact cupula in both the PSC and LSC. Cooling
      increased, while warming decreased the discharge. These responses are possibly
      due to a mechanism other than mechanical volume change, because the PSC and LSC
      yielded the same type of responses. Direct temperature reaction of the vestibular
      hair cell was suggested.

PMID- 9547492
TI  - Viewing distance related sensory processing in the ascending tract of deiters
      vestibulo-ocular reflex pathway.
AB  - The firing behavior of seven antidromically identified ascending tract of Deiters
      (ATD) neurons was recorded in one alert squirrel monkey trained to pursue moving
      targets and to fixate visual targets at different distances from the head during
      whole body rotation. 2. ATD cells generated signals related to contralateral
      horizontal smooth pursuit eye movements and to ipsilateral angular and linear
      head velocity. Most ATD neurons reversed the direction of their response to head
      rotation when the vestibulo-ocular reflex was canceled by fixation of a head
      stationary target. 3. ATD unit gains in respect to linear head velocity increased
      dramatically (> 4x) when a near, earth stationary target (10 cm from the eyes)
      was fixated, compared to the response recorded during fixation of a far target
      (130 to 170 cm from the eyes). Since the viewing distance related changes in the
      responses of ATD neurons closely parallel the changes in the responses of the
      eyes, the ATD appears to be an important premotor pathway for producing viewing
      distance related changes in the gain of the vestibulo-ocular reflex.

PMID- 9547493
TI  - The LNT model is appropriate for the estimation of risk from low-level (less than
      100 mSv/year) radiation, and low levels of radon in homes should be considered
      harmful to health.

PMID- 9547494
TI  - The linear no-threshold debate: where do we go from here?
AB  - For the past several years, the LNT (linear no-threshold) theory has come under
      attack within the scientific community. Analysis of a number of epidemiological
      studies of the Japanese survivors of the atomic bombings and workers exposed to
      low level radiation suggest that the LNT philosophy is overly conservative, and
      low-level radiation may be less dangerous than commonly believed. Proponents of
      current standards argue that risk conservatism is justified because low level
      risks remain uncertain and it is prudent public health policy; LNT opponents
      maintain that regulatory compliance costs are excessive, and there is now
      substantial scientific information arguing against the LNT model. Regulators use
      the LNT theory in the standards setting process to predict numbers of cancers due
      to exposure to low level radiation because direct observations of radiation
      induced cancers in populations exposed to low level radiation are difficult. The
      LNT model is simplistic and provides a conservative estimate of risk. Abandoning
      the LNT philosophy and relaxing regulations would have enormous economic
      implications. However, alternative models to predict risk at low dose are as
      difficult to justify as the LNT model. Perhaps exposure limits should be based on
      model-independent approaches. There is no requirement that exposure limits be
      based on any predictive model. It is prudent to base exposure limits on what is
      known directly about health effects of radiation exposure of human populations.

PMID- 9547495
TI  - The linear no-threshold response: why not linearity?
AB  - ICRP and NCRP recommend risk coefficients for use in radiation protection that
      are based on a linear quadratic response in the low dose region. This is a
      derivative of the linear no threshold (LNT) hypothesis with allowance for low
      dose and dose rate effects. The risk coefficients are derived from the Lifespan
      Study of the A-bomb survivors but are supported by many other epidemiological
      studies some, such as occupational, at low doses. Nevertheless, the risk
      coefficients are uncertain and range (90% confidence intervals) over a factor of
      2-3 above and below the nominal values. Various possible dose responses in the
      low dose region are considered including those that may result from adaptive
      responses. Laboratory studies show linearity in some systems to doses as low as
      2.5 mGy. Epidemiological studies include several with significant excess risks at
      100 mGy or less with at least one at 10 mGy. The linear quadratic response seems,
      therefore, the most likely response in the very low dose region. Adopting the
      linear quadratic response in the low dose region does not prevent common sense
      judgements about dismissing small radiation risks. NCRP defined first a
      negligible individual risk (1987) and then an individual dose (1993) to encourage
      common sense judgements in the low dose region. More consideration might be given
      to dismissing minor risks in common sense applications in radiation protection.

PMID- 9547496
TI  - The linear no-threshold dose-effect relation: is it relevant to radiation
      protection regulation?
AB  - Official radiogenic cancer risk estimates for low-dose, protracted exposure
      conditions have been based on linear, no-threshold downward extrapolation from
      medium and high-dose effects among a population of A-bomb survivors, with the
      application of a downward correction for an assumed reduced biological
      effectiveness at low doses and low dose rates (DDREF correction). Neither in the
      follow-up of populations exposed to the high-dose A-bomb flash, nor from
      epidemiological data after low-dose occupational or medical irradiation is there
      any convincing evidence for this DDREF hypothesis--even less for a zero-effect
      threshold dose. To the contrary, for external low-dose exposures of nuclear
      workers or general populations, cancer risks per unit dose have been found to be
      about 1 order of magnitude larger than those derived from the Japanese survivors,
      with larger discrepancies for persons above 50 years of age, and for x-rayed
      fetuses. This may be due to a dose and dose-rate effect exactly opposite from
      that postulated by the DDREF assumption, and a dose-dependent bias due to
      selection for exceptionally high immune competence among the > 5 years A-bomb
      survivor cohort. Excess cancer mortality following occupational exposures to
      ingested fission products and radiation-associated teratogenic, genetic, and
      cancer detriment among diverse populations who had ingested small amounts of
      radioactivity after the precipitation of fallout at great distances from the
      Chernobyl nuclear explosion, suggest discrepancies of as much as 2 orders of
      magnitude with official risk estimates. Contrary to widely publicized statements,
      claiming that current regulations of population exposures are far too
      restrictive, thus unnecessarily costly for the radiation industries, the
      aggregate of radiation epidemiological evidence suggests that current standards
      are inadequate to protect public health.

PMID- 9547497
TI  - Writing software for the clinic.
AB  - Medical physicists often write computer programs to support scientific,
      educational, and clinical endeavors. Errors in scientific and educational
      software can waste time and effort by producing meaningless results, but errors
      in clinical software can contribute to patient injuries. Although the ultimate
      goal of error-free software is impossible to achieve except in very small
      programs, there are many good design, implementation, and testing practices that
      can be used by small development groups to significantly reduce errors, improve
      quality, and reduce maintenance. The software development process should include
      four basic steps: specifications, design, implementation, and testing. A
      specifications document defining what the software is intended to do is valuable
      for clearly delimiting the scope of the project and providing a benchmark for
      evaluating the final product. Keep the software design simple and
      straightforward. Document assumptions, and check them. Emphasize maintainability,
      portability, and reliability rather than speed. Use layers to isolate the
      application from hardware and the operating system. Plan for upgrades. Expect the
      software to be used in unplanned ways. Whenever possible, be generous with RAM
      and disk storage; hardware is cheaper than development and maintenance. During
      implementation, use well-known algorithms whenever possible. Use prototypes to
      try out ideas. Use generic modules, version numbering, unique file names,
      defensive programming, and operating system and language/compiler defaults. Avoid
      binary data files and clever tricks. Remember that real numbers are not exact in
      a computer. Get it right before making it faster. Document the software
      extensively. Test continuously during development; the later a problem is found,
      the more it costs to fix. Use a written procedure to test the final product
      exactly as a typical user would run it. Allow no changes after clinical release.
      Expect to spend at least an additional 50% of the initial development effort on
      testing, fixing errors, and getting the software into routine operation.

PMID- 9547498
TI  - A new approach to electron-beam reference dosimetry.
AB  - A new approach is proposed for electron-beam dosimetry under reference conditions
      and data necessary to use this approach are presented. The approach has the
      following features; it uses ion chambers and starts from an absorbed-dose
      calibration factor for 60Co to be consistent with the present proposal for the
      new AAPM photon-beam protocol; it uses R50 to specify the beam quality and the
      reference depth, dref = 0.6R50 - 0.1 (all quantities in cm), recommended by Burns
      et al. [Med. Phys. 23, 383-388 (1996)]; it has a formalism which is parallel to
      the kQ formalism for photon-beam dosimetry; it fully accounts for the impact on
      stopping-power ratios of realistic electron beams; it allows an easy transition
      to using primary standards for absorbed dose to water in electron beams when
      these are available. The equation for dose to water under reference conditions
      is; DWQ = MPionPgrQk'R50kecalND,w60Co. The term PgrQ is not needed with plane
      parallel chambers but corrects for gradient effects with cylindrical chambers and
      is measured in the user's beam. The parameter kecal is associated with converting
      the 60Co absorbed-dose calibration factor into one for an electron beam of
      quality Qe and contains most of the chamber to chamber variation. Calculated
      values of kecal are presented as well as Monte Carlo calculated Pwall values for
      plane-parallel chambers in a water phantom irradiated by a 60Co beam since these
      are needed to calculate kecal. The factor k'R50 is a function of R50 and converts
      the absorbed-dose calibration factor to that for the electron-beam quality of
      interest. Two analytical expressions are presented which are close to universal
      expressions for all cylindrical Farmer-like chambers and for well-guarded plane
      parallel chambers respectively. Calculated values are presented graphically for
      electron beams with energies between 5 and 50 MeV.

PMID- 9547499
TI  - A gradient inverse planning algorithm with dose-volume constraints.
AB  - An inverse planning algorithm for determining the intensity-modulated beams that
      will most closely generate a desired dose distribution is presented. The
      algorithm is three-dimensional and does not explicitly depend on beam energies
      and modalities. It allows a single prescription dose or a window of acceptable
      doses to be specified for the target, with additional constraints to account for
      under- or over-dosing. For the protection of organs at risk, it provides maximum
      dose and dose-volume constraints. The latter apply to the entire volume of the
      organ exposed to the corresponding dose levels. Several levels of each type of
      constraint, with varying penalty weights, may be specified for each organ. The
      objective function that serves as the measure of the goodness of the solution is
      of the least-squares type and is minimized using conjugate gradient methods.
      Typical clinical cases involving 40,000 points and 4000 rays to be determined
      require about 10 min of CPU time on a DEC AlphaStation. Results are presented for
      two clinical sites, prostate and lung. The optimization algorithm yielded plans
      that featured higher target dose homogeneity, compared with the human planner's
      plan, while selectively sparing more of the normal organs at the desired dose
      regions.

PMID- 9547500
TI  - Measurement of backscatter to the monitor chamber of medical accelerators using
      target charge.
AB  - A simple noninvasive method is described for determining the backscatter to a
      monitor chamber of a medical accelerator based on the measurement of charge
      deposited in the target. This method is compared quantitatively to the more
      elaborate telescopic method for photon beams of 6 MV and 15 MV on linear
      accelerators having mica and Kapton monitor chambers. The new target charge
      method gives results consistent with the telescopic method to within 0.3%.

PMID- 9547501
TI  - Calibration and characterization of beta-particle sources for intravascular
      brachytherapy.
AB  - The calibration of a catheter-based system to be used for therapeutic radiation
      treatment to prevent restenosis following interventional coronary procedures is
      described. The primary dosimetry was performed ionometrically using an
      extrapolation chamber equipped with a 1-mm diameter collecting electrode to
      measure absorbed dose in tissue equivalent plastic at a depth of 2 mm. These
      results are compared with measurements with radiochromic dye film, which is also
      used to characterize sources for axial and trans-axial uniformity, and to
      determine dose distributions at various depths. A protocol for dose calculation
      based on that of AAPM TG43 is suggested for these sources, and examples of its
      use are given for the calculation of the enhancement effect on dose rate from a
      single seed source due to neighboring seeds. Monte Carlo calculations were also
      performed to validate the measured results.

PMID- 9547502
TI  - Lithium borate TLD for determining the backscatter factors for low-energy x rays:
      comparison with chamber-based and Monte Carlo derived values.
AB  - Recently, new backscatter factors for low-energy x rays derived from Monte Carlo
      calculations have been recommended in the UK code of practice for kilovoltage
      dosimetry published by (IPEMB). As these data, presented as a function of half
      value layer, do not take account of the variation of the x-ray spectra for a
      given HVL, we have undertaken an experimental study in order to determine BSG for
      the beam qualities provided by a Darpac 2000 therapy unit. A RTL detector such as
      Li2B4O7:Cu and parallel-plate ion chambers specially designed for low-energy x
      ray dosimetry have been used. The results obtained show very good agreement
      between the TLD and the Monte Carlo calculations, confirming values obtained by
      other authors with lithium borate TLD. On the contrary, the results obtained with
      plane-parallel ion chambers show discrepancies up to 9% that are discussed.

PMID- 9547503
TI  - Physical imaging performance of a compact computed radiography acquisition
      device.
AB  - A comprehensive investigation of the physical imaging performance of a Philips
      AC3 computed radiography system using fifth-generation image plate technology has
      been undertaken. Measurements include characteristic response, modulation
      transfer function (MTF) and Wiener spectra (WS) for standard and high resolution
      image plates sampled at 10 pixels/mm. These results were used to calculate noise
      equivalent quanta (NEQ) and detective quantum efficiency (DQE) spectral
      descriptions of system performance. Luminescence noise and x-ray quantum noise
      components were separated. From an estimate of the luminescence noise power, the
      average system gain was calculated and results show a substantial improvement
      over earlier generations of computed radiography systems for standard image
      plates.

PMID- 9547504
TI  - Isolation and characterization of all-trans-retinoic acid-responsive genes in the
      rat testis.
AB  - By way of differential screening of testis cDNA libraries from vitamin A
      deficient (VAD) rats before and after administration of all-trans retinoic acid
      (ATRA), genes, the transcription of which was influenced by ATRA, were isolated.
      Most clones with an increased transcription encoded different subunits of the
      same mitochondrial protein complex, cytochrome c oxidase (COX). The mRNA
      expression of COX increased by a factor 3.9 +/- 1.5 (mean +/- SD, n = 4). This
      increased expression seems to reflect an increased energy demand in the ATRA
      supplemented VAD testis. Also, one gene was isolated, the transcription of which
      was reduced to about 70% by ATRA. This gene, sulfated glycoprotein 2 (Sgp-2), is
      a major secretion product of Sertoli cells, the function of which is still
      unknown. The effect of ATRA on Sgp-2 expression may be direct, since the promoter
      of Sgp-2 contains a putative ATRA-responsive element (RARE).

PMID- 9547505
TI  - Sequences and expression patterns of alkaline phosphatase isozymes in
      preattachment bovine embryos and the adult bovine.
AB  - We report the cloning and partial sequences of two novel bovine tissue-specific
      alkaline phosphatase (AP) isozymes (TSAP2 and TSAP3) from in vitro-produced
      bovine blastocysts. Using a reverse-transcribed polymerase chain reaction (RT
      PCR)-based assay for mRNA expression and in vitro-produced preattachment bovine
      embryos, TSAP2 mRNA was detected first at the four-cell stage prior to the major
      burst of embryonic transcription in cattle and TSAP3 at the eight-cell stage with
      the major burst in transcription. Furthermore, the transcription of TSAP2 and
      TSAP3 displays a curious "on-off" pattern during early cleavages between 40 and
      120 hr after insemination. Activity of bovine AP, measured by an azo-dye coupling
      technique, indicates that at least one AP isozyme is functional in oocytes and
      embryos throughout bovine preattachment development. However, maternal and
      embryonic-derived AP activity may have different cell-surface distributions. This
      novel expression pattern of the bovine AP isozymes could provide a useful tool
      for identifying and clarifying the events controlling transcription and gene
      expression during early embryo development.

PMID- 9547507
TI  - DNA ploidy abnormalities in rabbit preimplantation embryos are not increased by
      conditions associated with in vitro culture.
AB  - Possible adverse effects of in vitro culture-associated physical factors were
      studied in 3- and 4-day-old rabbit embryos. Laboratory conditions were mimicked
      by exposure to visible light (320-740 nm, 1600 lx) or decreased temperature (22
      +/- 1 degree C). Embryos were exposed for a 24-hr period followed by either
      immediate evaluation or an additional 24 hr of standard in vitro culture
      (darkness, 37 degrees C) and evaluation thereafter. Effects were assayed by
      cytophotometric measurement of the DNA content in Feulgen-stained cell nuclei and
      by cell number. The incidence of DNA aneuploid embryos and DNA aneuploid cell
      nuclei per embryo, as well as the average nuclear DNA content, was not
      significantly different between exposed embryos and controls. Both in vitro
      culture and reduced temperature caused a decrease in cell number. The temperature
      induced cell number decrease was reversible within 24 hr after return to 37
      degrees C. These results demonstrate that physical factors associated with in
      vitro culture do not increase DNA ploidy abnormalities in cultured
      preimplantation embryos.

PMID- 9547506
TI  - The identification and characterization of expression of Pftaire-1, a novel Cdk
      family member, suggest its function in the mouse testis and nervous system.
AB  - We have isolated a murine cDNA encoding for a novel putative Cdk-related protein
      kinase, which has been named Pftaire-1, by screening a testis cDNA library for
      new serine/threonine kinases. Pftaire-1 showed 50% and 49% amino acid identity
      with Cdk5 and Pctaire-3, respectively, and contains the eleven subdomains
      characteristic of the protein kinases. By northern blot analysis we detected two
      transcripts of approximately 5.5 and 4.9 kb in size. These transcripts were
      expressed at low level in all murine tissues tested, except in the brain, testis
      and embryo, where high expression was detected. Cellular localization of the
      mRNAs by in situ hybridization analysis shows that Pftaire-1 is expressed in late
      pachytene spermatocytes in the testis and in post mitotic neuronal cells both in
      the brain and the embryo, suggesting a role of Pftaire-1 both in the process of
      meiosis as well as neuron differentiation and/or function.

PMID- 9547508
TI  - Selective loss of mouse embryos due to the expression of transgenic major
      histocompatibility class I molecules early in embryogenesis.
AB  - Among the numerous hypotheses proposed to explain the absence of fetal rejection
      by the mother in mammals, it has been suggested that regulation of expression of
      the polymorphic major histocompatibility complex (MHC) at the fetal-maternal
      interface plays a major role. In addition to a lack of MHC gene expression in the
      placenta throughout gestation, the absence of polymorphic MHC molecules on the
      early embryo, as well as their low level of expression after midgestation, could
      contribute to this important biologic phenomenon. In order to test this
      hypothesis, we have produced transgenic mice able to express polymorphic MHC
      class I molecules early in embryogenesis. We have placed the MHC class la gene H
      2Kb under the control of a housekeeping gene promoter, the hydroxy-methyl
      glutaryl coenzyme A reductase (HMG) gene minimal promoter. This construct has
      been tested for functionality after transfection into mouse fibroblast L cells.
      The analysis of three founder transgenic mice and their progeny suggested that
      fetoplacental units that could express the H-2Kb heavy chains are unable to
      survive in utero beyond midgestation. We have shown further that a much higher
      resorption rate, on days 11 to 13 of embryonic development, is observed among
      transgenic embryos developing from eggs microinjected at the one-cell stage with
      the pHMG-Kb construct than in control embryos. This lethality is not due to
      immune phenomena, since it is observed in histocompatible combinations between
      mother and fetus. These results are discussed in the context of what is currently
      known about the regulation of MHC expression at the fetal-maternal interface and
      in various transgenic mouse models.

PMID- 9547509
TI  - Improved development of in vitro-derived bovine embryos by use of a nitric oxide
      scavenger in a cumulus-granulosa cell coculture system.
AB  - This study was conducted to examine the hypothesis that nitric oxide (NO) affects
      prehatching development of bovine oocytes fertilized in vitro. In experiment 1,
      inseminated oocytes were cultured in a cumulus-granulosa cell (CG) coculture
      system to which 0.008 or 0.04 mM of sodium nitroprusside (SNP), a spontaneous NO
      releaser, was added at 18 or 60 hr postinsemination. Embryo development was
      greatly (P < 0.001) inhibited by the addition of SNP, regardless of time of
      addition or SNP concentration. In experiment 2, eight-cell embryos were cultured
      singly in a defined medium, to which 0.0016, 0.008, or 0.04 mM of SNP was added.
      Development to the blastocyst stage was greatly (P < 0.001) decreased after
      addition of SNP compared with no addition. Higher (P < 0.02) concentration of NO
      metabolites was found in developmentally arrested embryos than in developing
      embryos at 144 hr postinsemination (experiment 3). In experiment 4, blastocyst
      formation of oocytes cocultured with CGs was significantly (P < 0.02) increased
      after addition of hemoglobin (Hb, 1 microgram/ml), an NO scavenger. Prehatching
      development of oocytes was significantly (P < 0.05) increased after addition of
      Hb at different time intervals (18, 60, or 144 hr postinsemination) in experiment
      5. Embryo development was not enhanced by Hb addition to the culture medium in
      the absence of CGs (experiment 6). Prehatching development of eight-cell embryos
      derived from a Hb-containing culture system was not promoted by the further
      addition of Hb after transfer of the embryos to a defined and CG-free single
      embryo culture system (experiment 7). In conclusion, NO, which may be secreted
      from CGs, has an inhibitory role in prehatching development of bovine oocytes
      fertilized in vitro, and use of an NO scavenger, Hb, in a coculture system
      enhances blastocyst formation.

PMID- 9547510
TI  - Paracrine effects of bFGF and KGF on the process of mouse blastocyst
      implantation.
AB  - Implantation is a complex process that requires the interaction of the
      blastocyst, and subsequently, that of the developing embryos with the
      endometrium. Several growth factors and cytokines are involved in implantation,
      but the details of their actions as related to the regulation of blastocyst
      implantation remain unclear. In the present study, the RT-PCR method was used to
      determine the gene expression of basic fibroblast growth factor (bFGF),
      keratinocyte growth factor (KGF), FGF receptor 1 (FGFR1), FGF receptor 2 (FGFR2),
      and KGF receptor (KGFR) in mouse embryos and in the stromal and epithelial cells
      of the uterine endometrium. Basic FGF and KGF mRNA were expressed in the
      endometrial cells, but were not expressed in the embryos. The mRNAs of receptors
      for bFGF and KGF were expressed in the blastocysts and in the in vitro implanting
      embryos, suggesting that bFGF and KGF may exert paracrine effects on blastocyst
      implantation. In this mouse model of blastocyst implantation, it was found that
      transforming growth factor alpha (TGF-alpha) at the concentrations of 1 ng/ml and
      10 ng/ml significantly enhanced the blastocyst attachment and trophoblast
      spreading and increased trophoblast surface area. Relatively high concentrations
      of bFGF (100-500 ng/ml) significantly enhanced the rates of blastocyst attachment
      and of trophoblast spreading and promoted the expansion of the surface area of
      the implanting embryos. Unlike the rates of blastocyst attachment and trophoblast
      spreading, the surface area of the spreading embryos was significantly increased
      by addition of KGF (1-100 ng/ml). These results suggest that the bFGF and KGF
      derived from the endometrial cells exert paracrine effects on the process of
      implantation by stimulating trophoblast outgrowth through their cognate
      receptors.

PMID- 9547511
TI  - Regulation of plasminogen activator in rat endometrial stromal cells: the role of
      epidermal growth factor.
AB  - The effect of epidermal growth factor (EGF) on the accumulation of plasminogen
      activator (PA) activity in the medium of cultured rat endometrial stromal cells
      isolated from uteri sensitized for the decidual cell reaction was examined.
      Treatment with EGF increased, in a concentration-dependent manner, PA activity in
      the medium. This effect was inhibited or greatly reduced by inhibitors of
      transcription and translation. Incubation of the cells with prostaglandin E2
      increased PA activity in the medium. Indomethacin, which inhibited prostaglandin
      accumulation in the medium, slightly but significantly decreased the EGF-induced
      increase in PA activity in the medium. As indicated by zymography and the use of
      amiloride in the PA assay, the activity in the medium was primarily urokinase
      type plasminogen activator (uPA). Finally, EGF caused an increase in the steady
      state uPA mRNA levels in the cells. These results provide evidence that EGF
      causes an increase in the secretion of uPA by rat endometrial stromal cells from
      uteri sensitized for the decidual cell reaction through a mechanism that involves
      an increase in steady-state uPA mRNA levels.

PMID- 9547512
TI  - Four isoforms of the signal-transduction and RNA-binding protein QKI expressed
      during chicken spermatogenesis.
AB  - Genes expressed during spermatogenesis undergo alternative initiation and
      alternative splicing and may be under the control of a coordinated mechanism of
      RNA processing. A family of proteins that combine features of signal-transduction
      and RNA-binding molecules could be instrumental in this process. We have
      characterized a cDNA from adult chicken testis that codifies a highly conserved
      member of the STAR protein family, the orthologue of the mouse quaking gene qki.
      The predicted chicken protein differs only in four amino acids from the
      corresponding mouse protein. Messages of 7, 6, and 5 kb are expressed
      differentially during chicken spermatogenesis. The 5-kb message, the predominant
      form in adult testis, presents heterogeneity in the coding region, showing
      insertions of 51 and 75 bp and a deletion of 24 bp, which gives rise to four
      possible isoforms of the protein.

PMID- 9547513
TI  - Association of protein kinase A type I with detergent-resistant structures of
      mammalian sperm cells.
AB  - The finding that flagellar movement in detergent-permeabilized sperm cells is
      restored when Mg ATP and cAMP are added implicated detergent-resistant protein
      kinase A (PKA) in the regulation of sperm motility. It is widely believed that
      only the PKA regulatory subunit RII can associate with the cytoskeleton and/or
      organelles. In this paper we used monoclonal antibodies against the PKA catalytic
      subunit and RI subunit and demonstrated that PKA type I is also associated with
      the sperm cytoskeleton. To our knowledge, this is the first report showing
      anchored PKA type I. This association was found in sperm of nonrodent mammalian
      species and, to a lesser extent, also in mouse sperm. The PKA catalytic subunit
      is bound to the cytoskeleton secondarily via its complex with the regulatory
      subunit. The detergent-resistant complexes of RI and catalytic subunits localize
      predominantly to the flagellum. Ultrastructural immunogold labeling revealed the
      association of detergent-resistant PKA type I with outer dense fibers (ODF) and
      the fibrous sheath (FS) but not with microtubules. This location is consistent
      with a proposed role of PKA in regulation of FS sliding on underlying ODF.

PMID- 9547514
TI  - Changes in lipid diffusibility in the hamster sperm head plasma membrane during
      capacitation in vivo and in vitro.
AB  - The technique of fluorescence recovery after photobleaching (FRAP) was employed
      on spermatozoa labeled with the fluorescent lipid analogue C14dil to provide two
      measures of lateral diffusion in the plane of the sperm plasma membrane during
      capacitation in vivo and in vitro: the diffusion coefficient (D) for C14dil and
      the fraction of C14dil that is free to diffuse (%R) within the domain. To
      evaluate changes in lipid diffusibility during capacitation in vivo, spermatozoa
      were recovered from the uterus within 30 min after ejaculation or from the
      oviduct at 2, 4, 6 and 8 hr after mating. To compare the changes which occur in
      vivo with those which occur during capacitation in vitro, caudal epididymal
      spermatozoa were incubated under capacitating or non-capacitating (control)
      conditions for 4 hr. Although transient changes in D occurred during the course
      of capacitation, there was no net change in D for either anterior (AH) or
      posterior head (PH) domains following capacitation in vitro or in vivo.
      Significant differences in the lipid diffusion coefficient between the two head
      domains were observed during the course of capacitation. A transient decrease in
      %R was observed for the AH domain during capacitation in vitro and incubation
      under control conditions, but no significant change in %R was observed in the AH
      domain during capacitation in vivo. A significant decline in %R of the PH domain
      was observed for spermatozoa during capacitation in vivo, in vitro and following
      incubation under non-capacitating conditions. These data indicate that the
      changes in the lipid diffusibility of the AH and PH domains which occur during
      capacitation in vivo exhibit both similarities and differences to those which
      occur during capacitation in vitro.

PMID- 9547515
TI  - Expression of germ cell nuclear factor (GCNF/RTR) during spermatogenesis.
AB  - Germ cell nuclear factor (GCNF/RTR), a novel orphan receptor in the nuclear
      receptor superfamily of ligand-activated transcription factors, is expressed
      predominantly in developing germ cells. In several mammalian species two GCNF/RTR
      mRNAs are present in the testis, with the smaller 2.3-kb transcript generally
      expressed at higher levels than the larger 7.4- or 8.0-kb transcript. In both the
      mouse and rat, the 2.3- and 7.4-kb GCNF/RTR transcripts were detected in isolated
      spermatogenic cells, but not in Sertoli cells. Expression of these transcripts is
      differentially regulated, with the larger 7.4-kb mRNA appearing earlier during
      testicular development. The major 2.3-kb transcript is expressed predominantly in
      round spermatids in the mouse and rat. In situ hybridization studies in the rat
      demonstrated that GCNF/RTR transcripts reach maximal steady-state levels in round
      spermatids at stages VII and VIII of the spermatogenic cycle, and then decline
      abruptly as spermatids begin to elongate. RNase protection assays were used to
      predict the 3' termination site of the 2.3-kb transcript. An alternative
      polyadenylation signal (AGUAAA) was identified just upstream of this termination
      site. These studies suggest that GCNF/RTR may regulate transcription during
      spermatogenesis, particularly in round spermatids just prior to the initiation of
      nuclear elongation and condensation.

PMID- 9547516
TI  - Targeting of the domain-specific integral membrane protein PM52 to the
      periacrosomal plasma membrane during guinea pig spermiogenesis.
AB  - The sperm plasma membrane is segregated into functionally, biochemically, and
      structurally distinct domains yet the protein sorting pathways and assembly
      mechanisms that assemble these domains during spermiogenesis are incompletely
      understood. We previously characterized two structurally related size-variant,
      integral membrane proteins of 52 kDa (PM52) and 35 kDa localized to the
      periacrosomal plasma membrane of guinea pig cauda epididymal spermatozoa
      (Westbrook-Case et al., 1994). In this study we used light and electron
      microscopic immunocytochemistry to define the expression pattern and sorting
      pathway that establishes the domain-specific distribution of PM52 during
      spermiogenesis. The PM52 is first expressed in acrosome-phase spermatids and it
      localizes exclusively to the cytoplasmic lobe. Immunoelectron microscopy revealed
      that both cytoplasmic vesicles and the plasma membrane of the cytoplasmic lobe
      labeled with anti-PM52. During early stages of expression, PM52 appeared to be
      absent from the head region, but significant PM52 accumulation over the spermatid
      head was noted in late acrosomal phase spermatids. Throughout spermiogenesis PM52
      extended posteriorly to the annulus, which represents a barrier preventing PM52
      diffusion into the posterior tail. Following the migration of the annulus to the
      midpiece-principal piece junction, PM52 began to disappear from the flagellar
      region and at the completion of spermiogenesis most of the PM52 was restricted to
      the acrosomal segment. Spermatids and epididymal sperm PM52 exhibited identical
      sizes by SDS-PAGE and immunoblotting, indicating that they are not
      proteolytically modified during epididymal maturation. The PM52 antibodies were
      also used to screen a guinea pig testis cDNA library, and sequence determination
      of full-length PM52 clones demonstrated identity of a sperm membrane protein
      recently termed "sperad" (Quill and Garbers, 1996). Membrane barriers and
      potential mechanisms establishing the domain-specific residence of PM52 are
      discussed.

PMID- 9547517
TI  - Phosphorylation of Shc proteins in human sperm in response to capacitation and
      progesterone treatment.
AB  - Several authors have demonstrated the involvement of tyrosine kinases during
      sperm capacitation and acrosome reaction. Shc proteins (p46Shc, p52Shc, and
      p66Shc) are cytoplasmic substrates of activated tyrosine kinases and are widely
      expressed in mammalian somatic tissues. Experiments were designed to demonstrate
      the presence of Shc in spermatozoa and to study its involvement in the signal
      transduction events leading to acrosome reaction. Anti-Shc antibodies strongly
      reacted with the acrosomal region of methanol-fixed human sperm. Only one Shc
      isoform (p52Shc) was detected on Western blot. To study the degree of
      phosphorylation of Shc during capacitation and acrosome reaction, sperm samples
      were divided into two groups: noncapacitated and capacitated/progesterone
      treated. Lysates from both groups were immunoprecipitated with anti
      phosphotyrosine antibodies and the precipitated (i.e., phosphorylated) proteins
      were tested with anti-Shc antibodies. The intensity of p52Shc was clearly
      increased in capacitated/progesterone-stimulated cells.

PMID- 9547518
TI  - Synthesis and biological activity of some 4-amino-3-cinnoline carboxylic acid
      derivatives. Part 4: 2,4-Dioxo-1,2,3,4-tetrahydropyrimido[5,4-c]cinnolines.
AB  - A series of new 2,4-dioxo-1,2,3,4-tetrahydropyrimido[5,4-c]cinnolines and their 3
      substituted derivatives were prepared. These compounds were obtained by
      cyclocondensation of the appropriate substituted 4-amino-3-cinnolinecarboxylic
      acid with urea or 4-amino-3-cinnolinecarboxamides with N,N'-carbonyldiimidazole
      (DCl), oxalyl chloride or diethyl carbonate. Most of these compounds showed a
      high sedative action in low doses.

PMID- 9547519
TI  - [Solid phase microextraction (SPME) of sample preparation during of a complex
      biological matrix in biotransformation studies].
AB  - Within the scope of the investigation of drug metabolism in keratinocytes solid
      phase microextraction (SPME) was investigated as a suitable method for sample
      preparation. The application of SPME is based on the fact, that a amount of
      analyte is absorbed by the polymer fiber at equilibrium, and the fiber is
      localized on a tip of a GC-syringe. The stable nitroxyl radical TEMPO (2,2,6,6
      tetramthylpiperidine-1-oxyl) and its apolar metabolite 2,2,6,6
      tetramethylpiperidine were analyzed by SPME and subsequent GC using thymol as
      internal standard. By means of the headspace-technique and an apolar fiber the
      recovery rate of TEMPO and the metabolite was nearly 100% and the precision was
      high. However, the results of the direct SPME were unsatisfactory. In comparison
      with conventional liquid/liquid extraction and solid phase extraction SPE the
      SPME proved the best results with regard to recovery rate and precision.
      Furthermore, the main advantages of SPME are the renunciation of organic
      solvents, the saving of time, the possibility to reuse the fiber about 100-150
      times and the option for a complete automatisation of the extraction procedure.

PMID- 9547520
TI  - Antimicrobial activity of organic thiosulfates (Bunte salts).
AB  - A number of organic thiosulfates (Bunte salts) were prepared from appropriate
      primary bromides or iodides. In the case of substrates with long aliphatic
      chains, an addition of benzyltrimethylammonium chloride as phase transfer
      catalyst was very successful. The Bunte salts obtained were tested for
      antibacterial and fungicidal activity by means of the agar disc-diffusion method
      and by assignation of the minimum inhibitory concentrations (MIC). It was found
      that the microorganisms Proteus vulgaris, Candida albicans and Staphylococcus
      aureus showed the highest sensitivity. Biological activity of the compounds
      studied was dependent on the length of the aliphatic chain. Among the
      investigated compounds, aliphatic thiosulfates with 10-13 carbon atom chain were
      the most potent.

PMID- 9547521
TI  - Antimycobacterial activity of 3'- and 4'-fluorothiobenzanilides.
AB  - On the basis of a preliminary study of the antimycobacterial activity of
      thiobenzanilides, a group of 3'-fluoro- and 4'-fluorothiobenzanilides has been
      synthesized and tested against Mycobacterium tuberculosis, M. kansasii, M. avium
      and M. fortuitum. The results of this study demonstrate that electron withdrawing
      groups increase the activity of thiobenzanilides and fluoro benzothioanilides
      against atypical strains which is higher then that of INH.

PMID- 9547522
TI  - Mannich bases of arylalicyclic ketones and related quaternary ammonium compounds
      with antileukemic properties.

PMID- 9547523
TI  - Comparison of reinforcement schedules in the reduction of stereotypy with
      supported routines.
AB  - The rates and durations of stereotypic behaviors in four adolescents with severe
      mental retardation were measured during two daily vocational training sessions
      and during contiguous periods of leisure in their special education classrooms.
      Vocational training was conducted in two different tasks, alternating across
      days. The task requirements for each participant were matched to each
      participant's learning and performance characteristics. The participants were
      exposed to a fixed ratio schedule of tokens exchangeable for food items on one
      task and to a variable interval schedule for the same consequences on the second
      task. The schedules were chosen as an initial test of a matching-law based
      prediction by Myerson and Hale (1984): Variable interval reinforcement for
      adaptive behavior will produce less allocation of responding to maladaptive
      behavior than will a ratio-based intervention. When work performances stabilized,
      the schedules of token delivery were reversed across the tasks and performances
      again stabilized. Results are reported for periods when work performances met
      stability criteria. Stereotypy occurred more during leisure than during
      vocational training under either schedule. The major differences in stereotypy
      between leisure and vocational training were differences in episode length rather
      than rate of onset. Onset of stereotypy in vocational training, however, occurred
      at higher rates under the interval schedule than under the ratio schedule in both
      tasks. The results are discussed in terms of Myerson and Hale's prediction and
      implications for further research and application.

PMID- 9547524
TI  - Behavior disorders in persons with mental retardation receiving antipsychotic
      medication.
AB  - The behavior disorders of mentally retarded individuals receiving antipsychotic
      medication and the relationship between behavior disorders and the daily dose of
      drug were investigated. Of 355 residents of residential facilities in Wakayama
      Prefecture, Japan (age range, 7-64 years), the problem behaviors of 54 subjects
      receiving antipsychotic drugs were compared to those of 52 subjects receiving
      anticonvulsants and of 202 subjects without any medication at all, using the
      Japanese version of the Aberrant Behavior Checklist (ABC-J). All five subscale
      scores of the ABC-J were significantly higher for the antipsychotic group than
      for those of the other groups, whereas only the Irritability subscale was
      prominent in the subjects receiving anticonvulsants. The mean chlorpromazine
      equivalent dose was higher in the subjects with severe/profound disability than
      in those with mild/moderate disability and correlated with the Hyperactivity
      subscale scores. The problem behaviors of individuals with mental retardation
      prescribed antipsychotic drugs were more severe than those without medication;
      more severe disability and higher Hyperactivity scores were associated with dose
      of antipsychotic drugs.

PMID- 9547525
TI  - The Motivation Assessment Scale: reliability and construct validity across three
      topographies of behavior.
AB  - The psychometric properties of the Motivation Assessment Scale (MAS) were
      examined. Specifically, reliability, internal consistency, and construct validity
      were estimated using 90 ratings of different problem behaviors among 86
      individuals with mental retardation. Data were analyzed under conditions of (a)
      three topographies of problem behavior and (b) two methods of calculation.
      Although reliability and internal consistency were generally poor, the results
      depended upon the above conditions. Factor analysis revealed that the four
      factors of the MAS differed from the subscale structure obtained in this study,
      proposed by the authors of the MAS. Thus, the construct validity of this scale
      was ambiguous. It is concluded that the MAS should be employed in conjunction
      with other instruments to assess the functional characteristics of problem
      behavior with individuals who have mental retardation.

PMID- 9547526
TI  - The treatment of severe self-injurious behavior by the systematic fading of
      restraints: effects on self-injury, self-restraint, adaptive behavior, and
      behavioral correlates of affect.
AB  - Severe self-injurious behavior (SIB) in people with mental retardation is
      difficult to treat when dangerously frequent or intense responding rules out
      functional analysis and interventions that permit free responding. This situation
      is common when restrictive devices, such as straight arm splints, are used. In
      this study, the effects of introducing flexion into a straight-arm splint, on
      SIB, self-restraint, adaptive behavior, and behavioral correlates of affect were
      examined for three individuals with severe mental retardation. Using single-case
      design methodology, for two individuals self-injury was reduced to zero, while
      the overall level of restriction was also significantly reduced. From the
      observed behavioral correlates of affect, there was no evidence of an increase in
      negative affect with the introduction of the new splint and the fading procedure,
      but there was evidence of an increase in positive vocalizations. Engagement in
      activities and social contact were not affected by the introduction of the new
      splint. The reasons for a decrease in SIB with a corresponding decrease in
      restriction in the absence of any manipulation of contingencies for SIB are
      discussed, with particular reference to stimulus control.

PMID- 9547527
TI  - Social-emotional characteristics of preschool-aged children referred for Child
      Find screening and assessment: a comparative study.
AB  - Differences in parent ratings of social-emotional behavior among young children
      referred for Child Find screening and assessment and nonreferred children were
      examined. Participants included 64 preschool-aged children referred for Child
      Find screening and assessment (CF group) and 64 preschool-aged children without
      such referrals or identified disabilities (Comparison group). The Comparison
      group was matched to the CF group by gender and age, using a randomized block
      procedure. Social-emotional behavior of the participants was assessed using
      parent ratings on the Preschool and Kindergarten Behavior Scale (PKBS), a social
      skills and problem-behavior rating scale for use with children aged 3-6. PKBS
      scores were found to classify the participants into their respective groups with
      a substantial degree of accuracy. Significant differences were found between the
      two groups in social skills and problem behavior scores, with the CF participants
      evidencing greater social skills deficits and problem behavior excesses than the
      participants in the Comparison group. An inspection of frequency distributions of
      the two groups revealed that children referred for Child Find screening were
      approximately four times as likely to have significant social deficits, and
      approximately six times as likely to have significant problem-behavior excesses
      than their nonreferred comparison peers. New validity evidence for the PKBS is
      provided, along with recommendations for future research and clinical practice
      with the Child Find population.

PMID- 9547528
TI  - Evaluating the reinforcing effects of choice in comparison to reinforcement rate.
AB  - A concurrent-operants arrangement was used to evaluate a boy's preference for a
      choice condition (in which he chose the reinforcement) over a no-choice condition
      (in which the therapist selected the reinforcement for him) when (a) these
      conditions produced equal rates of reinforcement and (b) lower rates of
      reinforcement were associated with the choice condition. The boy preferred the
      choice condition even when it resulted in a much less favorable rate of
      reinforcement than the no-choice condition (up to 4000% less).

PMID- 9547529
TI  - Task variation versus task repetition for people with profound developmental
      disabilities: an assessment of preferences.
AB  - An assessment of preferences between task variation and task repetition with four
      adults with profound developmental disabilities was implemented. After
      participants were exposed to both task variation and task repetition conditions,
      they were allowed to choose between them. Results showed that all participants
      had strong preferences; three preferred task variation and one task repetition.
      Aspects of the assessment and use of assessment data for planning daily work
      conditions were discussed.

PMID- 9547530
TI  - Regulation of phosphoinositide phospholipases by G-proteins.

PMID- 9547531
TI  - The effects of group II phospholipase A2 on ras-induced metastasis.

PMID- 9547532
TI  - Activation of Ca(2+)-sensitive cytosolic phospholipase A2 (cPLA2) in human
      platelets.

PMID- 9547533
TI  - Involvement of reactive oxygen species in phospholipase A2 activation: inhibition
      of protein tyrosine phosphatases and activation of protein kinases.
AB  - Activators of PKC in combination with vanadate induce massive formation of
      reactive oxygen species. The formation of ROS leads to suppression of protein
      tyrosine phosphatase activity and consequently to enhanced protein tyrosine
      phosphorylation. This culminates in the activation of the MAP-K cascade and of
      PLA2 (Scheme 1).

PMID- 9547534
TI  - High molecular weight phospholipase A2: its occurrence and quantification in
      human colon cancer and normal mucosa.

PMID- 9547535
TI  - (S)-type lipoxygenase and cyclooxygenase reaction box models characterizing the
      stereochemistry of the dioxygenation reaction.
AB  - In summary, these models provide a unifying stereochemical summary of the
      dioxygenation reactions catalyzed by (S)-type lipoxygenases or for the first
      dioxygenation step of prostaglandin H synthases.

PMID- 9547536
TI  - Activation of 5-lipoxygenase in whole polymorphonuclear leukocytes by arachidonic
      acid: evidence of cytosolic active enzyme.

PMID- 9547537
TI  - Intracellular distribution, activity, and Ca(2+)-dependent translocation of 12
      lipoxygenase in Lewis lung tumor cells.

PMID- 9547538
TI  - Cloning and sequencing of prostaglandin H synthetase from rat tracheal epithelial
      cells: structural evidence that a TPA regulated mRNA codes for the rat ortholog
      of murine PHS-1.

PMID- 9547539
TI  - Non-enzymatic rearrangement of leukotriene A4 to 5-keto-(7E,9E,11Z,14Z)
      eicosatetraenoic acid in aqueous media.

PMID- 9547540
TI  - Bromoacetamido-analogs of indomethacin and mefenamic acid affinity-label
      prostaglandin H2 synthase at two sites.

PMID- 9547541
TI  - Regulation of eicosanoid synthesis in liver macrophages.

PMID- 9547542
TI  - Comparison of arachidonic acid metabolism by normal, precancerous and neoplastic
      epithelial cell lines of the upper aerodigestive tract.

PMID- 9547543
TI  - Induction of prostaglandin endoperoxide synthase-1 (COX-1) in a human
      promonocytic cell line by treatment with the differentiating agent TPA.
AB  - Prostaglandin endoperoxide synthase (PGH synthase) is responsible for converting
      arachdonic acid to PGH2, the common precursor of prostaglandins. It has been
      shown previously that phorbol ester-induced differentiation of human promonocytic
      leukemia cell lines is accompanied by induction of PGH synthase enzyme and
      enhanced capacity to produce prostaglandins. However, the identity of the isoform
      of PGH synthase, i.e., PGH synthase-1 or -2, that is induced under these
      conditions has not been established. Northern and Western analyses revealed a
      dramatic increase in levels of PGH synthase-1 mRNA and protein levels within 24
      hr after treatment of THP-1 cells with phorbol ester. No significant increase in
      PGH synthase-2 mRNA or protein was observed. The increases in PGH synthase-1 were
      accompanied by an enhanced capacity of the cells to produce PGE2. The current
      findings indicate that expression of PGH synthase-1 is greatly enhanced in a
      promonocytic cell line by treatment with an agent that induces differentiation.

PMID- 9547544
TI  - X-ray crystallographic study of the structure of prostaglandin H synthase.

PMID- 9547545
TI  - Properties of prostacyclin synthase.
AB  - Prostacyclin synthase (PGIS) was isolated from bovine aortic microsomes after
      detergent solubilisation following purification by DEAE-Sephacel, immobilized
      metal affinity, and hydroxy apatite chromatography. The homogenous protein
      exhibited spectral characteristics of a heme-thiolate protein (P450) like the
      enzyme purified earlier from porcine microsomes and had an apparent mass of 52
      kDa on SDS/PAGE. Three peptides from an endoproteinase Lys-C digest were isolated
      and sequenced. An antiserum was prepared from rabbits and purified by affinity
      chromatography. This allowed Western blots of microsomes from cultured
      endothelial cells. After treatment with IL-1 the activity of the cells in
      producing 6-keto-PGF1 alpha increased about threefold over 27 h which was
      accompanied by an increase in PGIS mass. A monoclonal antibody was used to set up
      an ELISA which served for the quantitation of PGIS in bovine tissues.

PMID- 9547546
TI  - Regulation of prostaglandin H synthase-1 gene expression.

PMID- 9547547
TI  - Mammalian arachidonate 12-lipoxygenases.

PMID- 9547548
TI  - The three-dimensional structure of soybean lipoxygenase-1: an arachidonic acid 15
      lipoxygenase.

PMID- 9547549
TI  - Purification and characterization of the epidermal 8(S)lipoxygenase.

PMID- 9547550
TI  - The effect of 5-lipoxygenase-activating protein (FLAP) on substrate utilization
      by 5-lipoxygenase.

PMID- 9547551
TI  - Leukotriene A4 hydrolase: differential inhibition of the catalytic activities by
      divalent cations.

PMID- 9547552
TI  - Regulation of 12(S)-HETE production in tumor cells.

PMID- 9547553
TI  - Distribution of COX-1 and COX-2 in normal and inflamed tissues.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment
      of a number of inflammatory diseases and are believed to act via inhibition of
      the enzyme cyclooxygenase (COX). This enzyme catalyzes the conversion of
      arachidonic acid to the prostaglandins (PGs). Although commercially available
      NSAIDs are efficacious anti-inflammatory agents, significant side effects limit
      their use. Recently two forms of COX were identified-a constitutively expressed
      COX-1 and a cytokine-inducible COX-2. Potent anti-inflammatory agents like the
      glucocorticoids are known to inhibit specifically the expression of COX-2 while
      commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2.
      These findings have led to the hypothesis that toxicities associated with NSAID
      therapy are due to inhibition of the non-regulated or constitutive form of COX
      (COX-1), whereas therapeutic benefit derives from inhibition of the inducible
      enzyme, COX-2. We have examined the relative distribution of COX-1 and COX-2 in
      both normal and inflamed tissues and report that COX-1 expression dominates
      normal tissues while COX-2 mRNA is induced at the inflammatory site. Furthermore,
      compounds that selectively inhibit COX-2 are anti-inflammatory without gastric
      toxicity.

PMID- 9547554
TI  - Examination of prostaglandin H synthase-1 topology in the endoplasmic reticulum
      membrane.

PMID- 9547555
TI  - Coordinate regulation of the inducible forms of prostaglandin synthase and nitric
      oxide synthase in fibroblasts and macrophages.

PMID- 9547556
TI  - Molecular cloning of prostacyclin synthase from bovine endothelial cells.

PMID- 9547557
TI  - Interaction of PGH synthase isozymes-1 and -2 with nonsteroidal anti-inflammatory
      drugs.

PMID- 9547558
TI  - Dual effect of propranolol on the human platelet activation by thrombin:
      potentiation of free intracellular Ca2+ mobilization and inhibition of
      phospholipase D activity.

PMID- 9547559
TI  - Molecular diversity of prostanoid receptors; subtypes and isoforms of
      prostaglandin E receptor.
AB  - cDNA cloning of PGE receptors revealed that there are at least three distinct
      subtypes of the receptor derived from different genes, which are different in
      ligand binding character and signal transduction. They also distribute
      differently in the body and localize in different cells of the organ. The cloning
      study also revealed that multiple isoforms of EP3 are produced by alternative
      splicing of its mRNA, and that these isoforms show identical ligand binding
      properties but couple to different signal transduction pathways. Thus, our study
      has shown that the diversity of PGE actions in the body is elicited by the
      molecular diversity of its receptor mediating these responses.

PMID- 9547560
TI  - Molecular characterization and physiological functions of PAF receptors.

PMID- 9547561
TI  - Identification of the FP-receptor as a discrete entity by radioligand binding in
      biosystems that exhibit different functional rank orders of potency in response
      to prostanoids.
AB  - The definition of the FP-receptor is currently based on the functional potency of
      agonists. Functional studies suggest that the FP-receptor has particular
      sensitivity to PGF2 alpha and certain PGF2 alpha analogs but is also stimulated
      by PGD2 and PGE2. In order to examine the concept that these responses involve a
      single (FP) receptor, we compared functional responses with radioligand binding
      competition studies. In Swiss 3T3 cells, an identical potency rank order was
      obtained for Ca2+ transient signals and competition at binding sites for 3H-PGF2
      alpha and 3H-17-phenyl PGF2 alpha (i.e., 17-phenyl PGF2 alpha > PGF2 alpha > PGD2
      > PGE2), suggesting interaction at a single receptor. This conclusion was further
      supported by successive addition studies where cells pretreated with a maximally
      effective dose of PGF2 alpha were refractory to subsequent addition of PGF2
      alpha, PGD2, or PGE2 but not PDGF. We also performed competition binding studies
      in the rat colon and uterus as representative tissues where the functional
      potency rank order is inconsistent with an FP receptor or any other prostanoid
      receptor subtype. Radioligand binding studies involving 3H-17-phenyl PGF2 alpha
      and 3H-PGE2 in the rat colon and uterus indicated the co-existence of both FP and
      EP3 receptors according to the competition afforded by natural PGs and selective
      analogs for FP and EP3 receptors. Thus, the FP-receptor can be identified in a
      mixed population of prostanoid receptors and this lends further support to the FP
      receptor as a discrete entity.

PMID- 9547562
TI  - Cellular activation by thromboxane A2 and 8-EPI-PGF2 alpha.

PMID- 9547564
TI  - Prostaglandin receptors involved in inflammatory events.

PMID- 9547563
TI  - Modification on ligand binding to TXA2/PGH2 receptors by diethylpyrocarbonate.

PMID- 9547565
TI  - LTB4 receptor antagonists exacerbate T lymphocyte-mediated delayed
      hypersensitivity in guinea pigs.

PMID- 9547566
TI  - Isolation and cloning of human peroxisome proliferator activated receptor gamma
      cDNA.

PMID- 9547567
TI  - Structure and localization of the rabbit prostaglandin EP3 receptor.

PMID- 9547568
TI  - Prostaglandin regulation of gene expression and growth in normal and malignant
      tissues.

PMID- 9547569
TI  - Distinct signaling pathways mediate induction of c-fos by PGE2 in glomerular
      mesangial cells.
AB  - Prostanoids induce expression of several immediate-early genes but the molecular
      mechanisms underlying these responses remain poorly characterized. We have
      studied induction of the proto-oncogenc c-fos by PGE2 in mesangial cells as a
      model of gene regulation by prostanoids. PGE2 induced marked and transient
      accumulation of c-fos mRNA. Induction of c-fos by PGE2 and TxA2 did not correlate
      with induction of phospholipase C. Addition of exogenous cAMP failed to induce c
      fos mRNA, suggesting that activation of an EP2 receptor linked to adenylate
      cyclase did not account for induction of c-fos by PGE2. These data contrast with
      previous experiments in NIH 3T3 cells where PGE2 induced c-fos by a cAMP
      dependent mechanism. We further showed that PGE2 induces the c-fos gene by direct
      activation of the serum response element. Taken together these experiments
      provide evidence for a pathway linking a PGE2 receptor on the plasma membrane to
      transcriptional activation in the nucleus.

PMID- 9547570
TI  - Cytosolic 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid binding sites in
      carcinoma cells.
AB  - 12(S)-HETE stimulates gene and cell surface expression of the integrin GPIIb/IIIa
      in carcinoma cells. The cells have high affinity binding sites for 12(S)-HETE.
      Analyses of the subcellular distribution and size of these sites showed that
      cytosol was the predominant location and that the apparent molecular weight was
      close to 670,000. Besides cytosol, mitochondria, nuclei, and plasma membranes
      also contained 12(S)-HETE binding sites. The mainly cytosolic location of the
      binding sites is different from that of other eicosanoid receptors which are G
      protein coupled plasma membrane proteins of the rhodopsin gene family.

PMID- 9547571
TI  - DAG second messengers: molecular switches and growth control.

PMID- 9547572
TI  - Sphingolipid second messengers: tumor suppressor lipids.

PMID- 9547573
TI  - The role of protein kinase C in signal transduction, growth control and lipid
      metabolism.

PMID- 9547574
TI  - Tumor responsiveness to the metastasis-stimulatory effects of prostaglandin E2 is
      restricted by protein phosphatases.

PMID- 9547576
TI  - The role of lipid peroxidation products in the regulation of protein kinase C
      activity in vitro.

PMID- 9547575
TI  - Interactions between specific phosphoproteins during modulation of prostacyclin
      secretion in cultured bovine aortic endothelial cells.

PMID- 9547577
TI  - Role of protein kinase C and phosphatases in 12(S)-HETE-induced tumor cell
      cytoskeletal reorganization.
AB  - Adherent B16 amelanotic melanoma (B16a) cells exposed to fatty acid 12(S)-HETE, a
      lipoxygenase metabolite of arachidonic acid, demonstrated a gradual dissolution
      of stress fibers and bundling-together of vimentin. The 12(S)-HETE effects on
      tumor cell cytoskeleton appeared 5 min after treatment, became prominent
      approximately 15 min following stimulation, and generally disappeared by 30 min.
      Simultaneous treatment of cells with 12(S)-HETE and okadaic acid (OA) prevented
      disappearance of the 12(S)-HETE effects by 30 min. Quantitative double
      immunoblotting of actin and vimentin indicated that actin, but not vimentin,
      underwent a time-related depolymerization. On the other hand, enhanced
      phosphorylation of vimentin but not of actin was observed after 12(S)-HETE
      treatment. 12(S)-HETE-enhanced vimentin phosphorylation was abolished by protein
      kinase C (PKC) inhibitor calphostin C, thus suggesting the involvement of PKC.

PMID- 9547578
TI  - PX-52, A novel inhibitor of 14 kDa secretory and 85 kDa cytosolic phospholipases
      A2.
AB  - Previously we reported that PGBx, a prostaglandin oligomer with anti-inflammatory
      activity, inhibited 14 kDa phospholipase A2 (PLA2) activity and blocked
      arachidonic acid mobilization in prelabeled human neutrophils (Biochim. Biophys.
      Acta 1006:272-277, 278-286, 1989) This study describes a new inhibitor of
      phospholipase A2, PX-52, that also blocks agonist induced arachidonic acid
      mobilization in prelabeled cells. PX-52, a fatty acid polymer, inhibited
      hydrolysis of 14C-oleate labeled E.coli by a variety of 14 kDa PLA2s including
      human PMN, sperm, synovial fluid and disc, as well as porcine pancreas, N. naja,
      and bee venom in a dose-dependent manner with IC50s ranging from 1.0-3.7 uM.
      Inhibition of activity was comparable at different Ca2+ concentrations, but was
      relieved by increasing substrate concentration or by methylation of PX-52.
      Hydrolysis of [14C]-arachidonyl phosphatidylcholine by 85 kDa, cytosolic PLA2
      from U937 cells was similarly inhibited by PX-52, the IC50 = 5 uM. Arachidonic
      acid mobilization induced by A23187 in prelabeled human PMNs was blocked by PX
      52; IC50 = 10-15 uM while concentrations of up to 80 uM oleate had no effect.
      These results demonstrate that PX-52 inhibits the in vitro activity of secretory
      and cytosolic PLA2s and agonist-induced arachidonic acid release from human
      cells. Given its ability to block the arachidonic acid cascade, PX-52 may be
      useful in the control of inflammation.

PMID- 9547579
TI  - Hepoxilin A3 inhibits agonist-evoked rise in free intracellular calcium in human
      neutrophils.

PMID- 9547580
TI  - The discovery of LY293111, a novel, potent and orally active leukotriene B4
      receptor antagonist of the biphenylphenol class.

PMID- 9547581
TI  - Inhibition of leukotriene B4 (LTB4) in human neutrophils by L-threo
      dihydrosphingosine.
AB  - The sphingosine analog L-threo-dihydrosphingosine has been shown to inhibit
      protein kinase C (PKC) isoenzymes in mixed micelle and vesicle assays. This
      compound also inhibited the reactive oxygen intermediates (ROI) released from
      isolated neutrophils (IC50 approximately 2 microM) and phorbol ester-induced
      edema and neutrophil influx in the mouse ear model (ED50 approximately 11 mg/kg).
      Based on the anti-inflammatory activity of this compound, studies were done to
      determine its effect on arachidonate metabolism by the lipoxygenase pathway.
      Neutrophils were preincubated with test agents or vehicle for one minute and then
      incubated with 1 microM calcium ionophore A23187 for two minutes. Supernatants
      were assayed for LTB4 using a radioimmunoassay. The reference lipoxygenase
      inhibitor nordihydroguaiaretic acid exhibited 98.3% inhibition at 1 microM (n =
      2) and prevented ROI production (IC50 approximately 6 microM). In contrast, the
      potent PKC inhibitor staurosporine was inactive against LTB4 in these studies (<
      23% inhibition at 10 microM, n = 2), but inhibited ROI formation (IC50
      approximately 3nM). L-threo-dihydrosphingosine inhibited LTB4 production 96.9 +/-
      1.3%, at 10 microM (IC50 = 6 microM, n = 2). These data suggest that L-threo
      dihydrosphingosine blocks the release of LTB4 from human neutrophils via a
      mechanism independent of PKC.

PMID- 9547582
TI  - Aspirin and gastrointestinal cancer.
AB  - In rodents, nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin
      inhibit chemically induced adenomas and early carcinomas of the colon. The NSAID
      Sulindac inhibits the growth of polyps of the colon and rectum in two randomized
      trials of patients with familial adenomatous polyposis (FAP), although the
      inhibition is not complete. Eight epidemiologic studies have found a 40-50%
      reduction in polyps or colorectal cancer among persons who regularly use aspirin
      or other NSAIDs compared to those who do not. Two epidemiologic studies show a
      slight increase in risk. Interpretation of the epidemiologic studies is
      complicated, because bleeding induced by aspirin may enhance the diagnosis and
      early treatment of cancer, and at least in theory, the symptoms of cancer could
      cause patients to avoid aspirin. Clinical trials designed specifically to
      investigate the aspirin hypothesis in humans at high risk of colorectal polyps or
      cancer are needed to establish causality, and to define the optimal dose and
      drug. Experimental studies should further define the mechanism of tumor
      inhibition in animals.

PMID- 9547583
TI  - Monohydroxylated fatty acids in mouse epidermis papilloma quantification and
      stereochemical characterization.

PMID- 9547584
TI  - Negative growth regulation of oncogene-transformed mammary epithelial cells by
      tumor inhibitors.
AB  - Deregulated expression of Ras and myc oncogenes confers neoplastic transformation
      in non-tumorigenic mammary epithelial cells. Down-regulation of perturbed
      biomarkers prior to tumorigenesis may provide a means of effective
      chemoprevention. In vitro experiments were designed to i) identify specific
      molecular, endocrine and cellular biomarkers as quantitative end points for
      preneoplastic transformation, and ii) utilize these end points to evaluate
      chemopreventive efficacy of selected naturally-occurring and synthetic tumor
      inhibitors. Stable Ras and myc transfectants exhibited persistent expression of
      oncogene specific mRNA transcripts, altered estradiol biotransformation and
      enhanced anchorage-independent growth in vitro prior to tumorigenesis in vivo.
      Treatment of the transfectants with omega-3-fatty acid, indole-3-carbinol and
      tamoxifen individually suppressed the perturbed molecular, endocrine and cellular
      biomarkers in vitro. Thus, suppressed oncogene expression and altered estrogen
      metabolism may be important determinants for antiproliferative mechanisms in
      mammary tumor inhibition, providing useful end points for chemopreventive
      intervention of preneoplasia.

PMID- 9547585
TI  - Different expression of prostaglandin-H synthase isozymes and lipoxygenases
      during multistage carcinogenesis in mouse skin.

PMID- 9547586
TI  - Expression of two cPLA2 isoforms in mouse epidermis in vivo.

PMID- 9547587
TI  - Regulation of arachidonic acid release and metabolism by tumor promoters.

PMID- 9547588
TI  - Effect of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid on
      eicosanoid concentrations in rat liver.

PMID- 9547589
TI  - A mitogenic and hormonal signalling network regulate mammalian cell division
      commitment time.
AB  - A basic property of mammalian cells is to retain the mitogenically induced
      "commitment" to undergo DNA replication even in the absence of stimuli. Recent
      findings on PGF2 alpha and hormone-induced Swiss 3T3 cell multiplication, reveal
      that this crucial cell cycle event can be regulated by several signalling
      mechanisms.

PMID- 9547590
TI  - Growth inhibitory effects of thromboxane antagonists on breast cancer cell lines:
      a preliminary study.

PMID- 9547591
TI  - The rise and fall of ceramide and 1,2-diacylglycerol (DAG): modulation by
      transforming growth factor-beta 1 (TGF beta 1) and by epidermal growth factor
      (EGF).
AB  - Transforming growth factor beta 1 (TGF beta 1) increases the phosphorylation of
      the epidermal growth factor (EGF) receptor and inhibits the growth of A431 cells,
      but the mechanism of TGF beta 1 signaling is unknown. Recent studies from this
      and other laboratories suggest a novel sphingomyelin signal transduction pathway
      (1-4). Ceramide, which is generated by sphingomyelinase action, can be deacylated
      to sphingoid bases, which are potential inhibitors of protein kinase C (PKC).
      Ceramide appears to have bioeffector properties. Cell-permeable ceramide analogs
      stimulate monocytic differentiation of human leukemia (HL60) cells (1), as well
      as the phosphorylation of the EGF receptor at Thr669 in A431 human epidermoid
      carcinoma cells (2). Further studies (3,4) demonstrate the existence of a
      ceramide-activated protein kinase (CAPK) that may mediate some of these aspects.
      The present studies aim to investigate the mechanism of TGF beta 1 signaling and
      to explore whether TGF beta 1's pathway involves activation of PKC by 1,2
      Diacylglycerol (DAG) and/or stimulation of a CAPK by ceramide. Ceramide and DAG
      levels of A431 cells are determined by thin layer chromatography (TLC) after
      treatment with either TGF beta 1 or with EGF. 100 pM TGF beta 1 treatment for 1
      hr increases the cellular contents of DAG 2-fold. 20 nM EGF treatment for 15 min
      decreases it 0.5-fold. Ceramide levels are reduced 2-fold by TGF beta 1 and
      almost unaffected by EGF. To evaluate the involvement of other components of
      signal transduction, the effects of TGF beta 1 and EGF on PKC activity are
      studied. 20 nM EGF decreases membrane PKC activity to 0.5-fold of controls,
      whereas 100 pM TGF beta 1 treatment of A431 cells increases this activity 4-fold.
      Modulation of PKC activity is paralled by translocation of the enzyme between the
      cytosol and the membrane as determined by Western immunoblot analysis. These
      studies suggest that TGF beta 1 and EGF may have regulatory effects on both
      sphingolipid and phospholipid metabolisms which could transmodulate both the CAPK
      and the PKC mediated signal tranduction pathways.

PMID- 9547592
TI  - Antioxidant defence mechanisms and PGE secretion by different types of
      transformed and tumor cells: in vivo selective advantages.

PMID- 9547593
TI  - The relationship between farnesylation and carcinogenesis: the effect of
      lovastatin on fibroblast proliferation.

PMID- 9547594
TI  - Eicosanoid production and growth regulation in rat intestinal epithelial cells.

PMID- 9547595
TI  - Role of arachidonic acid and linoleic acid metabolism in epidermal growth factor
      initiated proliferation of Syrian hamster embryo fibroblasts.

PMID- 9547597
TI  - Structural requirements for enhancement of EGF-dependent DNA synthesis by
      oxygenated metabolites of linoleic acid.

PMID- 9547596
TI  - Phenylacetate and phenylbutyrate as novel, nontoxic differentiation inducers.
AB  - Phenylacetate and analogs represent a new class of pleiotropic growth regulators
      that alter tumor cell biology by affecting gene expression at both the
      transcriptional and post transcriptional levels. Based on these findings, NaPA
      and NaPB entered clinical trials at the National Cancer Institute. Ongoing phase
      I studies with NaPA, involving adults with prostate and brain cancer, have
      confirmed that therapeutic levels can be achieved with no significant toxicities,
      and provide preliminary evidence for benefit to patients with advanced disease
      (Thibault et al., submitted).

PMID- 9547598
TI  - Decreased DNA synthesis in SCC-25 cells with ETYA and SC41661.

PMID- 9547600
TI  - Induction of 12-lipoxygenase expression by epidermal growth factor is mediated by
      protein kinase C in A431 cells.

PMID- 9547601
TI  - Prostaglandin F2 alpha (PGF2 alpha) triggers protein kinase C (PKC) and tyrosine
      kinase activity in cultured mammalian cells.
AB  - Prostaglandin F2 alpha (PGF2 alpha) added to confluent resting Swiss 3T3 cells
      triggers tyrosine kinase (PTK) activation characterized by the phosphorylation of
      a set of 75, 86, 110 and 140 kD proteins. PGF2 alpha induces this event
      independently of PKC activation. However, both PKC and PTK activities appear to
      act concertedly to cause mitogenesis. Here we discuss their relevance in the
      control of mammalian cell division.

PMID- 9547599
TI  - Liver fatty acid binding protein and mitogenesis in transfected hepatoma cells.

PMID- 9547602
TI  - Mechanisms of the selective cytotoxic actions of certain essential fatty acids.
AB  - Polyunsaturated fatty acids (PUFA) have a selective cytotoxic/cytostatic effect
      on a number of tumor cell lines in culture. Although this process may be enhanced
      by the addition of iron there is a minimum level of PUFA necessary for
      potentiation of cell death. Vitamin E blocks PUFA cytotoxicity when added up to 5
      days after fatty acid administration. Levels of thio-barbiturate reactive
      material (TBARM) in the medium rise in parallel with cell death. However, they
      are not affected by small alterations in temperature or oxygen tension.
      Incubating cells with PUFA causes marked alterations in the fatty acid patterns
      of both neutral and phospholipid fractions. Membrane fluidity is increased and
      the activity of membrane-bound receptors may be influenced directly or through
      the actions of eicosanoids derived from the exogenous fatty acid. PUFA may be an
      effective way of influencing tumor growth and a safe approach for the management
      of human cancer.

PMID- 9547603
TI  - Eicosanoids, cancer metastasis, and gene regulation: an overview.

PMID- 9547604
TI  - Radiation-induced apoptosis in tumors: effect of radiation modulating agents.

PMID- 9547605
TI  - Prostaglandin E2 mediated apoptosis in subsets of malignant B lymphoma cells.

PMID- 9547606
TI  - 13-HODE dehydrogenase activity as a modulator of intestinal cell differentiation.

PMID- 9547607
TI  - Effect of GM-CSF on leukotriene B4 synthesis in human neutrophils: facilitation
      of the priming effect by autologous plasma.

PMID- 9547609
TI  - Regulation of 15-lipoxygenase expression by cytokines.
AB  - The arachidonate 15-lipoxygenase is induced in peripheral human monocytes by
      culturing the cells for 3 days in the presence of interleukin 4 (IL-4) in
      concentrations as low as 40 pM. Linoleic acid is oxygenated by IL-4 treated
      monocytes to 13(S)-hydroxy-9Z, 11E-octadecadienoic acid [13(S)-HODE] with a
      specific activity of about 2 nmoles 13(S)-HODE/10(6) cells min. A screening of
      various permanent cell lines expressing the IL-4 receptor indicated that all
      monocyte/macrophage lines tested did not exhibit the effect of LOX induction.
      However, IL-4 treatment of the lung carcinoma cell line CCC 185 and of the colon
      carcinoma cell line HTB 38 induces the 15-LOX as shown by activity assay and
      immunohistochemistry. The IL-4 mutant Y124D which has been characterized as
      specific IL-4 receptor antagonist in human T-cells does not induce the 15-LOX but
      appears to act as competitive inhibitor for the induction. Subcellular
      fractionation of IL-4 treated monocytes indicated a cytosolic and a membrane
      bound enzyme pool. The intracellular action of the LOX leads to a specific
      oxygenation of the membrane phospholipids which is drastically increased after
      damage to the cells. The possible biological role of the 15-LOX for monocyte
      metabolism is discussed.

PMID- 9547608
TI  - Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial
      cell production of interleukin-6.
AB  - The interaction between lymphocytes, cytokines, and endothelial cells (EC) is a
      key step in the inflammatory process. Interleukin-6 (IL-6) a pleiotropic cytokine
      in its effects, seems to be an early indicator of acute systemic inflammation. In
      this study, we have examined the effects of polyunsaturated fatty acids (PUFAs)
      on the production of IL-6 by human unstimulated EC or EC stimulated with TNF
      alpha (100 U/ml); IL-4 (100 U/ml); LPS (1 ug/ml); or allogeneic peripheral blood
      lymphocytes (PBL). Twenty-four hour culture supernatants of immunoreactive IL-6
      were measured by Sandwich ELISA. We have shown that the production of IL-6 was
      potentiated when EC were stimulated with TNF-alpha; IL-4; LPS; or monocyte
      depleted PBL in comparison to unstimulated EC. The addition of n-3 PUFAs in
      culture medium (100 ug/ml DHA or EPA) significantly reduces the production of IL
      6 by unstimulated EC; or stimulated with TNF-alpha; IL-4 pg/ml); LPS or depleted
      PBL respectively for DHA and EPA, whereas the n-6 PUFAs (Arachidonic acid), even
      used at the highest concentration, was ineffective. This inhibitory effect is
      PUFA dose dependent but is more potent with EPA than DHA. Regardless of the mode
      of action, since IL-6 is known to be involved in hematopoiesis, in the regulation
      of the immune response and in the inflammatory reaction, these results suggest
      that n-3 PUFAs may play a role in suppressing inflammation. Further studies are
      needed to elucidate the mechanism involved and the choice between the two fatty
      acids for clinical and therapeutic purposes.

PMID- 9547610
TI  - Modulating effect of omega-3 fatty acids on the proliferative pattern of human
      colorectal mucosa.

PMID- 9547611
TI  - Agonist-induced lipoxin A4 generation in vitro and in aspirin-sensitive
      asthmatics: detection by a novel lipoxin A4-ELISA.

PMID- 9547612
TI  - Regulation of inducible prostaglandin G/H synthase by interleukin-1, transforming
      growth factors-alpha and -beta, and prostaglandins in bone cells.

PMID- 9547613
TI  - Potential role of heat shock transcription factor in the expression of
      inflammatory cytokines.

PMID- 9547614
TI  - Transcellular pathways and cell adhesion as potential contributors to leukotriene
      and lipoxin biosynthesis in acute glomerulonephritis.

PMID- 9547615
TI  - Lipoxin metabolism by human promyelocytic leukemia (HL-60) cells.

PMID- 9547616
TI  - IL-1 increases the ability of human endothelial cells to transform linoleic acid
      into monohydroxy-isomers and their incorporation into cell lipids.

PMID- 9547617
TI  - Apoptosis in tumor biology and therapy.

PMID- 9547618
TI  - Integrin functions and signal transduction.

PMID- 9547619
TI  - Regulation of tumor cell motility by 12(S)-HETE.

PMID- 9547620
TI  - Inhibition of mouse B16 melanoma cell motility by sphingosine-1-phosphate.

PMID- 9547621
TI  - Effects of leukotrienes B4 (LTB4) and D4 (LTD4) on motility of isolated
      normodense human eosinophils and neutrophils.
AB  - The effects of exogenous leukotrienes B4 and E4 (LTB4, LTD4) on the under-agarose
      motility of isolated normodense human eosinophils and neutrophils were examined
      using a novel sampling strategy for quantitation of leukocyte migration distance
      and vectorial orientation. Eosinophil chemotaxis to LTD4 was evident at a 10(
      10)M threshold. The selective peptide-LT antagonist, SK&F 104353, abolished LTD4
      induced eosinophil migration, indicating pharmacological specificity of the
      response. Neutrophil chemotaxis was apparent only with a very high (10(-5)M LTD4
      concentration. LTB4 was a potent eosinophil and neutrophil chemoattractant over a
      10(-9)M to 10(-4)M dose range. Analysis of leukocyte orientations provided
      evidence that chemokinetic responses were not being interpreted as indications of
      chemotactic behavior. LTB4 and LTD4 significantly altered neutrophil vectorial
      orientation. Comparison of migration distance and orientation at the leading edge
      and at the periphery of the well seeded with cells suggested that cell
      polarization appeared to be the earliest response to chemoattractive LTs. These
      results indicate that chemoattractant responses to LTs may be identified by
      utilizing the under-agarose technique and computer assisted analysis of cell
      orientation.

PMID- 9547622
TI  - 12(S)-HETE increases the motility of prostate tumor cells through selective
      activation of PKC alpha.
AB  - Prostate carcinoma has become the second most fatal cancer in American men. In
      rat Dunning prostate adenocarcinoma cells, increased cellular motility has been
      associated positively with their increased metastatic potential. However, the
      mechanism(s) responsible for regulation of tumor cell motility is poorly
      understood. We have reported that a lipoxygenase metabolite of arachidonic acid
      12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] augments tumor cell metastatic
      potential through activation of protein kinase C (PKC). We report here that 12(S)
      HETE increased the motility of AT2.1 cells and this 12(S)-HETE increased motility
      was inhibited by PKC inhibitor calphostin C. Western blot analysis revealed that
      AT2.1 cells expressed the Ca(2+)-dependent PKC isoform alpha and Ca(2+)
      independent PKC isoform delta. Pretreatment of cells with a Ca2+ chelator BAPTA
      blocked the 12(S)-HETE increased motility. Further, the motility of AT2.1 cells
      was increased in a dose dependent manner by thymelea toxin, a selective PKC alpha
      activator. Our data demonstrate that 12(S)-HETE augments the motility of AT2.1
      cells via its selective activation of PKC alpha which may serve as a key target
      for the development of antimetastatic drugs useful for combating prostate
      cancers.

PMID- 9547624
TI  - Enhancement of metastatic potential in a murine fibrosarcoma line by exposure to
      Corynebacterium parvum-elicited macrophages; effect of eicosanoid biosynthesis
      inhibition.

PMID- 9547623
TI  - Role of complex gangliosides in the integrin-dependent adhesion of cells in
      culture.

PMID- 9547625
TI  - A regulatory role of prostaglandin E2-activated adhesion molecules in
      myelopoiesis.

PMID- 9547626
TI  - Efficacy of Cicaprost on metastasis in advanced tumor disease.

PMID- 9547627
TI  - Post-translational regulation of surface integrin expression in tumor cells by
      12(S)-HETE.

PMID- 9547628
TI  - Eicosanoid 12(S)-HETE upregulates endothelial cell alpha V beta 3 integrin
      expression and promotes tumor cell adhesion to vascular endothelium.

PMID- 9547630
TI  - Radioprotection by misoprostol (PGE1 methyl analog) in combination with vitamin
      E, selenomethionine and WR-3689794.

PMID- 9547629
TI  - Dietary fatty acids alter the adhesion properties of lymphocytes to extracellular
      matrix proteins.
AB  - Dietary fats have been shown by many investigators to affect immune responses in
      vitro and in vivo. However, the exact mechanism(s) by which fats or their
      metabolic derivatives affect immune function is still unknown. In this report we
      have investigated whether short-term in vitro exposure to fatty acids alters the
      adhesion of lymphocytes to extracellular matrix proteins. We found remarkably
      heterogeneous effects with these agents on lymphocyte adhesion; increases and
      decreases in adhesion were observed depending upon the fatty acid, cell type and
      extracellular matrix protein used. Alterations in the adhesion potential of
      lymphocytes could serve as a mechanism for the reported effects of fatty acids on
      immune function since lymphocytes are dependent upon rapid and reversible
      adherence events for most of their effector activities.

PMID- 9547631
TI  - Behavioral and radioprotective effects of misoprostol in adrenalectomized mice.

PMID- 9547632
TI  - Effects of eicosanoid radioprotectors on rat motor performance.

PMID- 9547633
TI  - Protection from radiation-induced oral mucositis by a mouth rinse containing the
      prostaglandin E1 analog, misoprostol: a placebo controlled double blind clinical
      trial.

PMID- 9547634
TI  - Interleukin, radiation, and thermoregulation.

PMID- 9547635
TI  - Tumor radiosensitization based on the use of inhibitors of the mevalonate pathway
      of cholesterol synthesis.

PMID- 9547636
TI  - Synergistic protection of irradiated mice by a combination of iloprost and
      misoprostol.

PMID- 9547637
TI  - Regulation of the biosynthesis of the sulphido-leukotrienes.

PMID- 9547638
TI  - The role of lipid peroxidation in growth suppression of human breast carcinoma by
      dietary fish oil.

PMID- 9547639
TI  - Misoprostol: a potent cytotoxic and oncogenic radioprotector.

PMID- 9547640
TI  - Modification of radiation-induced gastrointestinal and hematopoietic injury in
      mice by combinations of agents: effects of indomethacin and caffeine.

PMID- 9547641
TI  - Anti-inflammatory drug treatment of radiation injuries.

PMID- 9547642
TI  - Low dose radiation induces endothelial cell eicosanoid metabolism and
      cytoskeletal rearrangement.

PMID- 9547643
TI  - Nonlethal gamma radiation displays similar cytoplasmic rearrangements as 12(S)
      HETE.
AB  - Timar et al. (Int. J. Canc., 52:594-603, 1992) and Onoda et al. (Rad. Res.,
      130:281-288, 1992) implicated 12(S)-HETE and nonlethal gamma radiation
      respectively, in enhanced expression of the alpha IIb beta 3 integrin receptor in
      B16a tumor cells. 12(S)-HETE has been reported to induce rearrangement of
      cytoplasmic elements and movement of cytoplasm (Haddad and Taylor, Proc. Amer.
      Cancer Res., 34:51, 1993); Timar et al., Cell Motil. Cytoskel., 26:49-65, 1993).
      Here, we report similar results in B16a tumor cells by post 90 cGy gamma
      radiation. Control cells were circular without cytoplasmic processes with the
      majority of their organelles and elements in perinuclear regions both surrounded
      by a ring of actin microfilaments. The cell's extensive leading edge was
      organelle free with the exception of occasional endoplasmic reticular cisternae
      parallel to one or two microtubules, and short bundles of actin microfilaments
      perpendicular to the plasma membrane. As early as 5 sec, but better defined by 60
      90 sec, one end of elongated microfilaments bundles became associated with the
      plasma membrane while the other end of the bundles became associated with
      perinuclear mass protrusions. By 5 min, prominent by 15 min, protrusions, now
      separated from the leading edge by mixture of bundle and ring microfilaments,
      reached the plasma membrane to form cellular processes. By 30 min, some
      cytoplasmic masses showed signs of retraction along with the disappearance of
      their associated mixed microfilaments. As well as numerous vesicles of unknown
      origin, primarily associated with microtubules perpendicular to the plasma
      membrane, mitochondria and endoplasmic reticular cisternae were found in the
      cytoplasmic masses.

PMID- 9547645
TI  - Impairment in the fatty acid composition of keloids.

PMID- 9547644
TI  - Dietary arachidonic acid increases eicosanoid production in the presence of equal
      amounts of dietary eicosapentaenoic acid.
AB  - Previously, we demonstrated that dietary n-3 PUFA (1.5%, w/w) effectively
      inhibited the production of eicosanoids derived from tissue arachidonic acid (AA)
      (Whelan et al., 1991). More recently, we also reported that dietary AA (1.0%,
      w/w) significantly augmented platelet and macrophage eicosanoid production in
      vitro (Whelan et al., 1993). This present study was designed to investigate the
      antithetic relationship of dietary AA and EPA on eicosanoid production in vivo.
      Forty-nine CD-1 male mice were randomly divided into four dietary groups.
      Identical diets were supplemented with ethyl esters (1.5%, w/w) of the following
      fatty acids: oleic acid (OA), AA, EPA or AA + EPA (A + E). After four weeks on
      diet, peritoneal cells were stimulated in vivo with opsonized zymosan and
      analyzed for eicosanoid production (PGE2, 6-keto-PGF1a, TXB2, LTE4, LTB4, LTE5
      and LTB5). The pooled eicosanoid production in the AA group was 41% and 300%
      higher compared to the OA (control) and EPA groups, respectively. Pooled
      eicosanoid production in the EPA group was 47% that of the OA group. When
      equivalent amounts of AA and EPA (AA + EPA) were included in the diet, the pooled
      eicosanoid production was 29% and 274% higher compared to the OA and EPA groups,
      respectively. These data demonstrate that dietary AA (1) enhances eicosanoid
      production in vivo and (2) abrogates virtually all of the effects observed with
      dietary EPA when both are included in the diet. The clinical implications of
      dietary AA as modulated by increased eicosanoid production could be significant,
      particularly when n-3 PUFA are used to reduce eicosanoid-mediated events.

PMID- 9547646
TI  - Linoleic acid levels in cutaneous tumors with different growth patterns as an
      additional sensitive diagnostic feature.

PMID- 9547647
TI  - The importance of linoleic acid in the total fatty acid compositions of benign
      and malignant neuroglial tumors.

PMID- 9547648
TI  - Dietary fat and energy modulation of biochemical events in tumor promotion.

PMID- 9547649
TI  - Chemoprevention of colon cancer by dietary administration of naturally-occurring
      and related synthetic agents.

PMID- 9547650
TI  - Diradylglycerol formation is altered by n-3 highly unsaturated fatty acids, with
      differences between eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids.

PMID- 9547651
TI  - Arachidonic acid metabolites in saliva of patients with squamous cell carcinoma
      of the head and neck.

PMID- 9547652
TI  - Preparation of two dosage forms containing antitumor prostaglandin and their
      antitumor effect in vitro and in vivo: Lipiodol solution for i.a. administration
      and lipid microspheres for i.p. or i.v. administration.

PMID- 9547653
TI  - Urinary excretion of prostanoids in children with chronic pyelonephritis.

PMID- 9547654
TI  - Interaction of phospholipase C-gamma with activated growth factor receptor
      tyrosine kinases.

PMID- 9547655
TI  - Prostanoid and anti-thrombin III levels in premature infants.

PMID- 9547656
TI  - Molecular biology of prostanoid biosynthetic enzymes and receptors.

PMID- 9547657
TI  - Tumor infiltrating lymphocytes in squamous cell carcinoma of the head and neck:
      mechanisms of enhancement using prostaglandin synthetase inhibitors.
AB  - Indomethacin has been shown clinically to inhibit growth of SCCHN (Panje, 1981).
      This inhibition appears to be due to augmentation of cellular immunity. The
      inhibitory effect of indomethacin may act by limiting tumor associated
      prostaglandin E2 production, thereby allowing return of costimulatory cytokines
      by antigen presenting cells. This would have the net result of relief from host
      unresponsiveness and promotion of B-cell and CTL differentiation, allowing the
      individual to mount an effective response. The enhancement of tumor infiltrating
      lymphocytes in SCCHN seen with indomethacin administration could presumably be
      further augmented when given in combination with cytokine therapy. Future
      investigation may allow the biochemical staging of an individuals' tumor to
      determine the optimal combination of cytokine therapy and prostaglandin
      inhibition through selective use of NSAID's. The effect of NSAID manipulation of
      prostaglandin and leukotriene metabolism on prevention of metastatic disease in
      SCCHN has yet to be studied. Given that a preselected, potentially responsive
      subset of immunocytes exists within the tumor tissue and lymph nodes, the
      development of the LAK phenomenon in TIL's and tumor draining lymph nodes from
      surgical specimens is a viable and exceedingly interesting area for future
      investigations in autologous LAK immunotherapy. The potential exists to harvest a
      preselected population of tumor infiltrating (Boscia, 1988) or tumor draining
      immunocytes (McKinnon, 1990). These can then potentially be returned to a state
      of antigen responsiveness with a combination of cytokine exposure (e.g. rIL-2)
      and systemic cytokine therapy. With subsequent inhibition of tumor associated
      prostaglandin synthesis by the systemic administration of prostaglandin synthesis
      inhibitors, it may be possible to successfully alter the host response to tumor.

PMID- 9547658
TI  - An empirical analysis of eating disorder, not otherwise specified: preliminary
      support for a distinct subgroup.
AB  - OBJECTIVE: In recent years, there has been debate concerning whether distinct
      subgroups exist within the eating disorder, not otherwise specified (EDNOS)
      diagnostic category. One subgroup that has been suggested is binge-eating
      disorder (BED). While BED has received some research attention, relatively little
      is known about other possible subgroups within the EDNOS category. The purpose of
      the present study is to empirically investigate whether distinct subgroups exist
      within the diagnostic category of EDNOS. METHOD: Participants were 53 EDNOS
      patients who presented to psychotherapy clinics for treatment of an eating
      disorder. Information gathered from a clinical assessment, which included a
      clinical interview and self-report questionnaires, was used in the analyses of
      the study. RESULTS: Using cluster analytic procedures, two subgroups of patients
      diagnosed with EDNOS were identified. The two subgroups differed from each other
      in terms of weight, binging, and body image variables. Specifically, the second
      subgroup (of 11 patients) appeared to be a distinct subgroup of overweight binge
      eating patients, while the first subgroup appeared to be a heterogenous group of
      EDNOS patients. The overweight binge-eating subgroup was significantly higher in
      current weight, in reported highest adult weight, in reported higher lowest adult
      weight, and had more binges per week than the heterogenous EDNOS subgroup.
      Interestingly, the two subgroups did not differ in terms of self-reported purging
      and/or compensatory behaviors (e.g., vomiting and laxative use). DISCUSSION: The
      results of the present study provide preliminary support for a distinct subgroup
      within the EDNOS diagnostic category. This subgroup resembles BED, with the
      exception of the presence of purging behaviors. The findings of the present study
      suggest the need to further investigate the exclusionary criteria of
      purging/compensatory behaviors for the BED diagnosis.

PMID- 9547659
TI  - Relations of restraint and negative affect to bulimic pathology: a longitudinal
      test of three competing models.
AB  - OBJECTIVE: Although theorists have proposed that restraint and negative affect
      cause bulimia nervosa, it is possible that bulimic pathology promotes restraint
      and negative affect, or that bulimic symptoms are reciprocally related to these
      two factors. The present study tested these competing models. METHOD:
      Longitudinal data from a community sample of adolescent females (N = 218) was
      used to test these alternative models. RESULTS: Prospective correlations
      suggested that bulimic pathology was reciprocally related to both restraint and
      negative affect. However, in more stringent tests controlling for the temporal
      stability of these factors, restraint was not related to subsequent bulimic
      symptoms, but bulimic pathology predicted future restraint. Negative affect and
      bulimic symptoms were not related over time when the stability of these factors
      was controlled, but they did show contemporaneous reciprocal relations.
      DISCUSSION: Results provide some support for the negative affect model of
      bulimia, but raise questions about the restraint model.

PMID- 9547660
TI  - A comparison of purging and nonpurging eating-disordered outpatients: mediating
      effects of weight and general psychopathology.
AB  - OBJECTIVES: The present study compared purging and nonpurging eating-disordered
      outpatients on key behavioral and psychological features of their disorder. It
      also investigated the possible mediating effects of current level of depression,
      anxiety or general psychopathology, and current weight on differences between
      purgers and nonpurgers. METHOD: Seventy-seven patients from an outpatient eating
      disorder clinic who purged were compared to 48 clinic patients who did not purge
      on measures of eating behavior disturbances and specific psychopathology while
      controlling for weight, level of depression, anxiety, and general distress.
      RESULTS: Purgers reported significantly more eating behavior disturbance and
      higher scores on measures of specific psychopathology than the nonpurgers. These
      differences were unrelated to current weight, level of anxiety, or general
      distress. However, severity of depression did moderate some of the difference
      between the groups. CONCLUSION: These data provide further support for the
      proposition that purging is a distinctive clinical marker in all types of eating
      disordered patients.

PMID- 9547661
TI  - Motivations for running and eating attitudes in obligatory versus nonobligatory
      runners.
AB  - OBJECTIVE: This study examined the association between motivations to run and
      eating disturbances in a sample of obligatory and nonobligatory runners. METHOD:
      240 males and 84 females were evaluated for running habits, motivations for
      running, and eating and weight concerns. 26.2% of the men and 25% of the women
      were classified as obligatory runners. RESULTS: Obligatory runners were more
      motivated to run by negative factors such as guilt for stopping, scored
      significantly higher on the Eating Attitudes Test (EAT), and had lower weights.
      These effects were strongest in women. DISCUSSION: The results suggest that
      female obligatory runners may be at increased risk for eating disorders.

PMID- 9547662
TI  - The relationship between alexithymia, depression, and axis II psychopathology in
      eating disorder inpatients.
AB  - OBJECTIVE: The major purpose of this study was to examine alexithymia in
      relationship to depression and Axis II psychopathology in eating disorder
      patients. METHOD: Fifty-three female inpatients representing three DSM-IV eating
      disorder diagnostic groups and 14 control subjects completed the Toronto
      Alexithymia Scale (TAS), the Eating Disorder Inventory-2, and the Beck Depression
      Inventory within the first week of their hospital admission and shortly before
      discharge. Structured Clinical Interviews for DSM-III-R (SCID) I and II were also
      conducted. Multiple regression analyses were used to determine the contribution
      of mood, diagnostic, and personality variables in predicting the alexithymia
      score. RESULTS AND DISCUSSION: After controlling for depression, only the TAS
      factor, "difficulty expressing feelings," remained significantly different
      between groups, with the anorexia nervosa-restrictors (AN-R) having significantly
      higher scores than controls and bulimia nervosa patients. This factor appears to
      be a relatively stable personality characteristic in AN-R. The level of
      depression and the presence of avoidant personality disorder were the most
      predictable variables for the alexithymia total score.

PMID- 9547663
TI  - Body weight preoccupation in middle-age and ageing women: a general population
      survey.
AB  - OBJECTIVE AND METHODS: The desired weights and dieting behavior of a sample of
      1,053 women aged 30-74 years in the general population of Geneva, Switzerland,
      were explored by means of a questionnaire. Multivariate analyses of variance were
      performed. RESULTS: Twenty-five percent of the women were satisfied with their
      weight, whereas 71% wanted to be thinner, although 73% of them were at normal
      weight. Among women older than 65 years, 62% wanted to lose weight, 65% of them
      being at normal weight. For women wanting to lose weight, mean desired weight
      loss amounted to 9% of their current weight. Weight dissatisfaction increased
      with higher education (p < .001), and with increasing current weight (p < .001).
      Within the last 5 years, 42% of the women had dieted for weight control,
      including 67% at normal weight. Thirty-one percent of the women older than 65
      years had also dieted, 62% of them being at normal weight. DISCUSSION: A majority
      of middle-age and ageing women in this general population sample expressed
      dissatisfaction about their weight. Many attempted dieting, even when they were
      at normal weight. Considering the vulnerability of the elderly to nutritional
      deficiencies, dieting to lose weight in normal weight ageing women should be
      discouraged or closely monitored.

PMID- 9547664
TI  - The slender ideal and eating disorders: an interdisciplinary "telescope" model.
AB  - OBJECTIVE: This paper interprets eating disorders (including anorexia and
      bulimia) as one (nonfunctional) manifestation, in modern environments, of evolved
      psychological mechanisms which modulate the standard of feminine bodily
      attractiveness as a response to economic conditions. METHOD: Published evidence
      from anthropology, sociology, and psychology was used to evaluate predictions
      that (1) where economic independence is possible, women favor a slender standard
      and (2) where women lack economic power, marriage tends to be favored and the
      standard becomes more curvaceous. These patterns were tested by correlating U.S.
      economic data with changing standards of bodily curvaceousness in Vogue and
      Playboy. Psychological and biological mechanisms by which the slender standard
      produces anorexia and bulimia were examined. RESULTS: Published evidence and the
      empirical data suggest that the standard of bodily curvaceousness is determined
      by the economics of reproduction. DISCUSSION: These ideas permit integration of
      the research on eating disorders in several disciplines and suggest many avenues
      for future enquiry.

PMID- 9547665
TI  - The role of family status and ethnic group on body image and eating behavior.
AB  - OBJECTIVE: To examine the role of ethnic group and family status on body
      dissatisfaction and eating behavior. METHOD: One hundred women (Asian mothers and
      daughters, n = 50; white mothers and daughters, n = 50) completed a questionnaire
      about their perceived ethnic identity (acculturation), body image, and eating
      behavior. RESULTS: The results showed no matching between mothers and daughters
      and no effect of acculturation on body image and eating behavior. However,
      mothers reported greater body dissatisfaction and white subjects reported higher
      levels of restrained eating. In addition, the results showed a significant Ethnic
      Group x Family Status interaction for both body image and eating behavior
      irrespective of body mass index (BMI). Accordingly, white daughters were found to
      be the most dissatisfied with their bodies and most concerned with the calorie
      content of their food, followed by the Asian mothers. White mothers were found to
      be the most satisfied with their body and Asian daughters were the least
      concerned with calories. DISCUSSION: The results are discussed in terms of the
      changing nature of media images in both Asian and white cultures and the impact
      of the transition between these two cultures.

PMID- 9547666
TI  - An ethnic comparison of eating attitudes and associated psychological problems in
      young British women.
AB  - OBJECTIVE: The study aimed to investigate possible differences in eating
      attitudes/problems and associated psychological problems in young women of
      differing ethnic origin. METHOD: In a city with a relatively high Asian
      population (with a background in the Indian subcontinent), 235 young women aged
      18-27 registered with a general practice responded to a postal questionnaire. The
      questionnaire examined eating and weight problems (including the 26-item Eating
      Attitudes Test), self-esteem (measured by the Rosenberg Self-Esteem Scale), and
      general psychological well-being (measured by The Hospital Anxiety and Depression
      Scale). We also included three short vignettes designed to assess illness
      perception and health seeking-behavior. RESULTS: We found relatively little
      difference in eating attitudes and problems according to ethnicity, although self
      induced vomiting for weight control was more common among Caucasian women.
      Neither was there any difference in self-esteem, anxiety, depression, and illness
      perception. DISCUSSION: The results suggest that one cannot generalize about
      eating problems across the Asian population and a more sophisticated approach to
      the examination of sociocultural factors is recommended.

PMID- 9547667
TI  - Well-being and morbid obesity in women: a controlled therapy evaluation.
AB  - OBJECTIVE: Morbidly obese individuals are unlikely to reach and maintain
      normative weights. Thus, interventions aimed at alleviating corollary problems,
      independent of attempts at weight loss, are appropriate. A cognitive group
      treatment program (CT) was developed which incorporated a nondieting approach,
      regular exercise, and use of alternative coping skills. Weight loss per se was
      not a focus of the intervention. The purpose of the current work was to evaluate
      this program in a controlled, comparative treatment outcome study. METHOD: Sixty
      two obese women with a history of treatment failures were randomly assigned to
      the CT program, a behavior therapy weight loss program (BT), or a wait-list
      control group. RESULTS: For CT participants, depression, anxiety, and eating
      related psychopathology decreased significantly over the course of treatment
      while perceptions of self-control increased; BT and control subjects showed no
      significant changes in these variables. Women in both active treatment groups
      lost significant amounts of weight, while members of the control group showed a
      nonsignificant increase in weight. At 6-month follow-up, treatment benefits were
      maintained. DISCUSSION: Findings suggest that interventions not directly aimed at
      weight loss can enhance psychological well-being and thus may be appropriate for
      some obese women.

PMID- 9547668
TI  - Does the Composite International Diagnostic Interview underdiagnose the eating
      disorders?
AB  - OBJECTIVE: A study was undertaken to assess the procedural validity of the
      Composite International Diagnostic Interview (CIDI) for the diagnosis of eating
      disorders. METHOD: The CIDI was administered to 44 patients consecutively
      admitted to an eating disorders unit. CIDI-generated diagnoses were compared with
      clinical diagnoses documented in patient files. Discrepancies between diagnoses
      were examined in detail. RESULTS: A significant level of disagreement was
      apparent, particularly for anorexia nervosa patients. A large number of patients
      with symptoms requiring inpatient treatment did not reach criteria using CIDI's
      diagnostic algorithm. CONCLUSION: Considerable difficulties remain in the use of
      standardized assessments, such as the CIDI, to diagnose eating disorders. While
      presenting features of the illness, for example, ego syntonic nature of the
      illness, secrecy, and denial, may be part of the reason, the questions used by
      the CIDI appear to be in need of some refinement.

PMID- 9547669
TI  - Multiple resistance modulators combined with carboplatin for resistant
      malignancies: a pilot study.
AB  - BACKGROUND: Chemotherapy resistance is probably multifactorial; hence, we
      assessed the feasibility of adding to carboplatin 6 concurrent resistance
      modulators in 53 patients with resistant cancers. METHODS: Pentoxifylline and
      dipyridamole were added to carboplatin 400 mg/m2 in cohort 1, and metronidazole
      was also given in cohort 2. Mannitol and saline were administered in each cohort
      with the theoretical objective of improving carboplatin delivery to tumors by
      reducing blood viscosity. Because of excessive toxicity in cohort 2, cohort 3
      received the same modulators as in cohort 2 but with a reduced dose of
      carboplatin (200 mg/m2). Subsequent patients had the following drugs added to
      those in the previous cohort: novobiocin (cohort 4), tamoxifen (cohort 5),
      ketoconazole (cohort 6). Cohort 7 patients received the 6 cohort 6 modulators
      along with carboplatin 300 mg/m2. RESULTS: Thrombocytopenia was excessive in
      early cohorts with a carboplatin dose of 400 mg/m2, but was minimal at lower
      doses. Other toxicity was generally tolerable and reversible, particularly at
      carboplatin doses < or = 300 mg/m2, although gastrointestinal and neurological
      toxicity tended to worsen as additional modulators were added. No major responses
      (but 4 minor responses) were seen in this patient population with heavily
      pretreated or primarily resistant cancers. CONCLUSIONS: Acceptable doses for
      phase II studies are carboplatin 300 mg/m2, 20% mannitol 250 ml plus normal
      saline 500 ml over 1 hr prior to carboplatin, pentoxifylline 700 mg/m2/day p.o.
      from 3 days before carboplatin to cessation of therapy, dipyridamole 100 mg/m2
      p.o. q6h x 6 days starting 24 hr before carboplatin, metronidazole (750 mg/m2
      p.o. 12 hr and immediately before, and 24 hr after carboplatin; 250 mg/m2
      suppository p.r. 12 hr and immediately before, and 6 and 24 hr after carboplatin;
      and 500 mg/m2 i.v. right after carboplatin), novobiocin 600 mg/m2 p.o. q12h x 6
      days starting 24 hr before carboplatin, and tamoxifen 100 mg/m2/day plus
      ketoconazole 700 mg/m2/day x 3 days starting the day before carboplatin, with
      oral dexamethasone and ondansetron as antimetics.

PMID- 9547671
TI  - An in vitro assessment of the antineoplastic potential of 2H-1,3-oxazine-2,6(3H)
      dione (3-oxauracil), a novel pyrimidine.
AB  - The pyrimidine (uracil) analogue 3-oxauracil (OU) previously had been shown to
      completely inhibit the growth of E. coli B and decrease by 96% the replication of
      herpes simplex virus type 2 when present in the culture fluid at a concentration
      of 10(2) microM. Limited in vivo studies in mice demonstrated antiviral effects
      without significant toxicity when given i.p. daily for two weeks at a
      concentration of 3.23 mg/kg. However, the antineoplastic properties of OU were
      unknown. We assessed the ability of OU to inhibit the proliferation of various
      human tumor cell lines (3 pancreatic, 1 colon, 1 neuroendocrine, and 1 lung) in
      an in vitro radiometric (Bactec) system. In the pancreatic lines (RWP-2, MiaPaCa
      2, and PANC-1), the colon line (HT-29), the neuroendocrine line (COLO 320DM), and
      the lung cancer cell line (SK-MES-1), OU at a concentration of 10(3) microM,
      produced a dramatic decrease in percent cell survival. When compared with
      cytotoxic drugs of choice for these tumor cells (gemcitabine, 5-fluorouracil, and
      adriamycin, respectively) a significantly higher concentration of OU was required
      usually to achieve comparable results with two exceptions. These were the HT-29
      and the COLO 320DM cell lines. These results indicate OU has significant (p <
      0.05) cytotoxic activity against pancreatic, colon, neuroendocrine, and nonsmall
      cell lung cancer lines, when compared to untreated control cultures. Additional
      in vivo testing of this potential antineoplastic agent is warranted.

PMID- 9547670
TI  - IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389
      IL-4).
AB  - Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and
      differentiation of various cell types as well as regulating other cytokines. To
      study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we
      first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells
      express a single 4 kB IL-4R-specific mRNA and 1828 +/- 408 high affinity IL-4
      binding sites per cell with a dissociation constant (Kd) of 154 +/- 37 pM.
      Addition of recombinant human IL-4 (rIL-4) minimally inhibited AIDS-KS cell
      growth and expression of IL-6. We then studied the effects of a chimeric fusion
      toxin DAB389-IL-4 which exerts cellular toxicity only on cells expressing IL-4R.
      DAB389-IL-4 inhibited protein synthesis in AIDS-KS cells at low concentrations
      (IC50 of 5 x 10(-11) M). This effect was abrogated by neutralizing antibody to IL
      4 (25D2). We conclude that KS cells express a functional IL-4R and this receptor
      could serve as a target for novel therapy with agents such as DAB389-IL-4.

PMID- 9547672
TI  - Preclinical toxicity of a new oral anticancer drug, CI-994 (acetyldinaline), in
      rats and dogs.
AB  - CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1
      clinical trials. To assess its preclinical toxicity, CI-994 was administered
      orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs
      (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats
      (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40,
      and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on
      toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at
      the highest dose in both species beginning on Day 10. Neutropenia,
      lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow
      hypocellularity, and testicular degeneration were observed in both species,
      primarily at the mid- and high-doses. Despite continued treatment, neutrophil
      counts in dogs returned to control levels in Week 2. Other microscopic findings
      in rats included splenic hematopoietic depletion at all doses and epithelial cell
      necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs
      involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid
      and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects
      in both species, all changes were reversible within a 4-week (rat) or 9-week
      (dog) recovery period. The results of these studies show that target organ
      effects of CI-994 principally involve tissues with rapidly dividing cell
      populations and that bone marrow suppression is the dose-limiting toxicity. CI
      994 also seems to interfere with the release and/or maturation of cells in the
      bone marrow.

PMID- 9547673
TI  - Potent induction of human colon cancer cell uptake of chemotherapeutic drugs by N
      myristoylated protein kinase C-alpha (PKC-alpha) pseudosubstrate peptides through
      a P-glycoprotein-independent mechanism.
AB  - Phorbol ester protein kinase C (PKC) activators and PKC isozyme over-expression
      have been shown to significantly reduce intracellular accumulation of
      chemotherapeutic drugs, in association with the induction of multidrug resistance
      (MDR) in drug-sensitive cancer cells and enhancement of drug resistance in MDR
      cancer cells. These observations constitute solid evidence that PKC plays a
      significant role in the MDR phenotype of cancer cells. PKC-catalyzed
      phosphorylation of the drug-efflux pump P-glycoprotein was recently ruled out as
      a contributing factor in MDR. At present, the sole drug transport-related event
      that has been identified as a component of the role of PKC in MDR is PKC-induced
      expression of the P-glycoprotein-encoding gene mdr1. The objective of this study
      was to test the hypothesis that PKC can modulate the uptake of chemotherapeutic
      drugs in cancer cells independently of P-glycoprotein. We analyzed the effects of
      selective PKC activators/inhibitors on the uptake of radiolabelled cytotoxic
      drugs by cultured human colon cancer cells that lacked P-glycoprotein activity
      and did not express the drug efflux pump at the level of message (mdr1) or
      protein. We found that the selective PKC activator 12-O-tetradecanoylphorbol-13
      acetate (TPA) significantly reduced uptake of [14C] Adriamycin and [3H]
      vincristine in human colon cancer cells devoid of P-glycoprotein activity, and
      that PKC-inhibitory N-myristoylated PKC-alpha pseudosubstrate synthetic peptides
      potently and selectively induced uptake of the cytotoxic drugs in the phorbol
      ester-treated and non-treated colon cancer cells. TPA treatment of the cells did
      not induce expression of either P-glycoprotein or its message mdr1. In contrast
      with [14C]Adriamycin and [3H] vincristine uptake, [3H] 5-fluorouracil uptake by
      the cells was unaffected by TPA and reduced by the PKC-inhibitory peptides. These
      results indicate that PKC activation can significantly reduce the uptake of
      multiple cytotoxic drugs by cancer cells independently of P-glycoprotein, and
      that N-myristoylated PKC-alpha pseudosubstrate peptides potently and selectively
      induce uptake of multiple cytotoxic drugs in cultured human colon cancer cells by
      a novel mechanism that does not involve P-glycoprotein and may involve PKC
      isozyme inhibition. Thus, N-myristoylated PKC-alpha pseudosubstrate peptides may
      offer a basis for the development of agents that reverse intrinsic drug
      resistance in human colon cancer.

PMID- 9547674
TI  - An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid
      and interferon-alpha: E2Y92.
AB  - The Eastern Cooperative Oncology Group conducted a Phase I trial to determine the
      maximally tolerated doses of combination therapy with alpha interferon (IFN
      alpha) and all-trans-retinoic acid (tRA). Fifty patients with incurable
      malignancies received IFN-alpha administered subcutaneously three times weekly,
      and tRA administered by mouth at bedtime. Doses were escalated between patient
      groups, starting at tRA dose level of 45 mg/m2 and 3 million units of IFN-alpha.
      Major, dose-limiting toxicities were attributable to either the tRA (rash,
      chelitis) or IFN (constitutional symptoms), and were observed only at tRA dose
      levels of 224 mg/m2 and 291 mg/m2, or 6 million units of IFN-alpha. The maximally
      tolerated dose level of 172.5 mg/m2 of tRA and 3 million units of IFN-alpha was
      well-tolerated, with no grade 3 or 4 toxicities attributable to therapy. One
      patient at the third dose level (75 mg/m2 of tRA and 3 million units of IFN
      alpha) developed acute hepatic and renal failure and a metabolic encephalopathy
      of unclear etiology. We conclude that tRA and IFN-alpha may be safely
      administered together at the maximally tolerated dose of tRA as a single agent
      without unexpected side effects. The recommended doses of IFN-alpha and tRA for
      Phase II trials are 3 million units of IFN-alpha and 172.5 mg/m2 of tRA.

PMID- 9547675
TI  - Phase I study of high dose etoposide phosphatase with filgrastim (G-CSF) in the
      treatment of advanced refractory malignancies.
AB  - PURPOSE: To define the maximum tolerated dose of etoposide phosphate when used
      with G-CSF in the treatment of patients with refractory malignancies. PATIENTS
      AND METHODS: Eleven patients with advanced cancer refractory to standard therapy
      were treated with etoposide phosphate given over 1-2 hours on three consecutive
      days. The first cohort of patients received a total dose of 1596 mg/m2
      (equivalent to etoposide 1400 mg/m2); doses were escalated in subsequent patient
      cohorts. G-CSF 5 micrograms/kg was administered subcutaneously from day 4 until
      the total leukocyte count rose to > 10,000/microL. Two courses were given at 28
      day intervals. RESULTS: Toxicity produced by high dose etoposide phosphate
      included myelosuppression and mucositis. Three of five patients treated at the
      2280 mg/m2 dose level (equivalent to etoposide 2000 mg/m2) had dose limiting
      toxicities (grade 4 leukopenia for 7 days, 2 patients; grade 4 mucositis +
      leukopenia, 1 patient). In addition, median days with severe thrombocytopenia (<
      50,000/microL) rose to six days at this dose. Other toxicity was uncommon.
      CONCLUSIONS: In pretreated patients, the maximum tolerated dose of etoposide
      phosphate with G-CSF is 1938 mg/m2 (equivalent to etoposide 1700 mg/m2). Dose
      limiting toxicities were myelosuppression and mucositis, as with high dose
      etoposide. Etoposide phosphate can be substituted for etoposide in high dose
      regimens; due to its greater solubility, administration can be more rapid,
      requires less fluid volume, and is not associated with acidosis.

PMID- 9547676
TI  - A phase I trial of weekly gemcitabine administered as a prolonged infusion in
      patients with pancreatic cancer and other solid tumors.
AB  - PURPOSE: Pharmacological studies of gemcitabine (2',2'-difluorodeoxycytidine)
      have shown that increased levels of the active triphosphate metabolite are
      achieved by prolonging infusion time while holding the dose rate constant. The
      primary aim of this study was to determine the maximum tolerated dose (MTD) of
      gemcitabine administered as a fixed rate infusion (10 mg/m2/min) on a weekly
      schedule in patients with untreated non-hematologic malignancies. PATIENTS AND
      METHODS: Twenty-seven patients (21 pancreatic adenocarcinoma, 3 hepatoma, 1
      neuroendocrine tumor, and 2 adenocarcinoma of unknown primary) were enrolled in
      this open-label, non-randomized study. Three different entry dose levels (1200
      mg/m2, 1500 mg/m2 and 1800 mg/m2) were evaluated for gemcitabine administered on
      days 1, 8, and 15 of a 28-day cycle. RESULTS: The MTD was defined as 1500 mg/m2
      with granulocytopenia and thrombocytopenia being dose-limiting. There were no non
      hematological dose limiting toxicities. The maximum WHO grade 3 or 4 toxicities
      for hemoglobin, leukocytes, neutrophils, and platelets for all doses of
      gemcitabine administered were 11.5%, 30.8%, 57.7%, and 26.9%, respectively. Non
      hematologic toxicities included nausea, vomiting and fever. Four patients were
      withdrawn from the study for non-hematological toxicities: pneumonitis, ascites,
      disabling fatigue, and an acute myocardial infarction. Two of these events were
      severe (pneumonitis and myocardial infarction) but these may not be related to
      drug administration. CONCLUSION: Gemcitabine administered at a rate of 10
      mg/m2/min was tolerated up to 1500 mg/m2 in patients with previously untreated
      non-hematologic malignancies. Myelosuppression seen in this study is more severe
      than anticipated based on previous reports of bolus administration of similar
      doses of gemcitabine. This supports earlier studies suggesting that prolonged
      duration of infusion increases the intracellular accumulation of active
      metabolites of gemcitabine.

PMID- 9547677
TI  - Long-term response to crisnatol mesylate in patients with glioma.
AB  - A total of 26 patients (6 with anaplastic astrocytoma; 20 with glioblastoma) were
      treated with crisnatol mesylate. All patients had residual or progressive disease
      following surgery and standard radiotherapy; nine patients had prior
      chemotherapy. Crisnatol was administered as a 72-hour infusion every 21 days at a
      starting dose of 2250 mg/m2. Two patients who had not received prior chemotherapy
      achieved a complete response and remain in continuous complete remission over
      seven and six years, respectively, post-diagnosis. Two other patients remained
      stable on crisnatol for 10 months before disease progression. One patient with
      mixed oligodendroglioma/glioblastoma progressed after 12 months on crisnatol. He
      survives at 7 years post-diagnosis, with Karnofsky Performance Status of 60
      following other therapies. One patient with anaplastic astrocytoma stopped
      treatment by request after 10 months and remains stable 64 months post diagnosis.
      Seventeen evaluable patients, including nine patients with prior chemotherapy,
      progressed after 2-9 courses of therapy. Median survival is 9.25 months, with a
      one year survival rate of 30% and 2 years survival rate of 17%. Neurotoxicity was
      acute and dose-limiting. Side effects were tolerable and limited to duration of
      infusion. Two complete, long-lasting responses to crisnatol mesylate in patients
      with progressive malignant glioma are encouraging results and warrant further
      investigation.

PMID- 9547678
TI  - A phase II study of 13-cis-retinoic acid in patients with advanced renal cell
      carcinoma.
AB  - The aim of this study was to determine the antitumor activity of 13-cis-retinoic
      acid as a single agent in patients with advanced renal cell carcinoma. Eligible
      patients had advanced renal cell carcinoma with bi-dimensionally measurable
      disease, a Karnofsky performance status of at least 70, life expectancy of
      greater than three months, no evidence of brain metastases, and treatment with no
      more than one chemotherapy regimen. Patients were treated with one mg/kg/day of
      13-cis-retinoic acid orally. Twenty-six patients were enrolled in this study and
      25 were evaluable for response and toxicity. Of the twenty-five evaluable
      patients, no major responses were achieved. Toxicity was mild, with no patient
      requiring a dose reduction. At the dose administered in this trial, 13-cis
      retinoic acid is inactive as a single agent in renal cell carcinoma.

PMID- 9547679
TI  - Phase II evaluation of topotecan in patients with advanced colorectal cancer. A
      Southwest Oncology Group trial (SWOG 9241).
AB  - The topoisomerase-1 inhibitor, topotecan, was tested in 48 eligible patients with
      advanced colorectal cancer. The patients had no prior chemotherapy and a
      Southwest Oncology Group performance status of 0-2. Topotecan was administered
      intravenously at 1.5 mg/m2/day for five days and repeated every 21 days. The
      major toxicity was hematologic with 19 out of 48 (40%) patients having grade IV
      granulocytopenia and 4 out of 48 (8%) patients demonstrating grade IV
      thrombocytopenia. Two patients (4%) demonstrated partial response. Thirty
      patients have died and the Kaplan-Meier estimate of median survival is 9 months
      (95% confidence interval; 7-16 months). Topotecan in this dose and schedule does
      not appear active in patients with advanced colorectal cancer.

PMID- 9547680
TI  - Phase II study of flutamide as second line chemotherapy in patients with advanced
      pancreatic cancer.
AB  - Androgen receptors are present in both pancreatic cancer tissue and cell lines.
      Flutamide is a potent antiandrogen widely used in clinical practice for patients
      with metastatic prostate cancer. This Phase II trial was undertaken to evaluate
      the impact of flutamide in patients with advanced pancreatic adenocarcinoma who
      had developed progressive disease following therapy with one 5-FU-based regimen.
      Fourteen patients were treated with flutamide, 250 mg orally three times per day.
      Therapy was generally well tolerated. No patients achieved objective tumor
      response. No patient had improvement in tumor-related symptoms as measured by
      improvement in pain intensity, analgesic requirement, performance status, or
      nutritional status. Median survival was 4.7 months. We conclude that flutamide is
      ineffective second line therapy for patients with advanced pancreatic
      adenocarcinoma.

PMID- 9547681
TI  - Improving functional outcomes in older patients: lessons from an acute care for
      elders unit.
AB  - BACKGROUND: Hospitalization often marks the beginning, and may be partially
      responsible for, a downward trajectory characterized by declining function,
      worsening quality of life, placement in a long term care facility, and death. At
      the University Hospitals of Cleveland, an Acute Care for Elders (ACE) unit that
      reengineered the process of caring for older patients (> or = 70 years of age) to
      improve functional outcomes was established in September 1990. DESCRIPTION OF
      INTERVENTION: The general principles of ACE included an approach to care guided
      by the biopsychosocial model and recognition of the importance of fitting the
      hospital environment to the patient's needs. The design of the intervention was
      consistent with principles of comprehensive geriatric assessment and continuous
      quality improvement. Care, which focused on maintaining function, was directed by
      an interdisciplinary team that considered the patient's needs both at home and in
      the hospital. The major components of the ACE Unit intervention included patient
      centered nursing care (daily assessment of functional needs by nursing, nursing
      based protocols to improve outcomes, daily rounds by a multidisciplinary team), a
      prepared environment, planning for discharge, and medical care review. RESULTS:
      In a randomized trial comparing ACE with usual care, patients receiving ACE had
      improved functional outcomes at discharge. The costs to the hospital for ACE unit
      care were less than for usual care. The functional status of ACE and usual care
      patients was similar 90 days after discharge. FUTURE DIRECTIONS: The ACE unit
      intervention is being expanded to preserve the improvements observed during the
      hospitalization in the outpatient setting. In addition, needs other than function
      which are critical to patients' long-term quality of life are being considered.

PMID- 9547682
TI  - Using a computerized sign-out program to improve continuity of inpatient care and
      prevent adverse events.
AB  - BACKGROUND: Many medical injuries are preventable, but there are few reported
      successful strategies to prevent such injuries. Previous work identified coverage
      by house staff not primarily responsible for the patient (cross-coverage) as a
      significant correlate of risk for preventable adverse events. A four-month
      intervention--computerized sign-outs--was introduced in 1993 in an urban teaching
      hospital to improve continuity of care during cross-coverage and thereby reduce
      risk for preventable adverse events. MEASUREMENTS: A previously tested
      confidential self-report system was used to identify adverse events, which were
      defined as unexpected complications of medical therapy that resulted in increased
      length of stay or disability at discharge. A panel of three board-certified
      internists confirmed events and evaluated preventability based on case summaries.
      RESULTS: After the intervention, the rate of preventable adverse events among the
      3,747 patients admitted to the medical service decreased from 1.7% to 1.2% (p <
      0.10). Both univariate and multivariate analysis revealed no association between
      cross coverage and preventable adverse events after the intervention. In the
      baseline period, the odds ratio (OR) for a patient suffering a preventable
      adverse event during cross coverage was 5.2 (95% confidence interval [CI], 1.5
      18.2; p = 0.01), but was no longer significant after the intervention (OR, 1.5;
      95% CI, 0.2-9.0). CONCLUSION: House staff are willing participants in efforts to
      measure and improve the quality of health care systems. The intervention may have
      reduced the risk for medical injury associated with discontinuity of inpatients
      care. Four years after the end of the study, the computerized sign-out program
      remained an integral part of the computing support system for house staff and was
      widely used.

PMID- 9547683
TI  - Quality indicators using hospital discharge data: state and national
      applications.
AB  - BACKGROUND: Demand for information about the quality of health care has
      escalated. Yet many organizations lack well-specified quality measures,
      statistical expertise, or the requisite data to produce such information. The
      Healthcare Cost and Utilization Project Quality Indicators (HCUP QIs) represent
      one approach to measuring health care quality using readily available data on
      hospital inpatients. METHODS: The HCUP QIs, developed in 1994, address clinical
      performance rather than other dimensions of quality such as satisfaction or
      efficiency. The 33 indicators produce rates that represent measures of outcomes
      (mortality and complications), utilization, and access. In lieu of complex
      multivariate techniques, two methods were used: (1) restrictions in defining
      patient subgroups to isolate homogeneous at-risk populations and (2)
      standardization when populations are diverse. Stratified analyses are recommended
      when patient or hospital factors are believed to influence the outcome. A simple
      method for making statistical comparisons to national rates was developed. The
      HCUP QI software, available in both mainframe and microcomputer applications,
      have enabled organizations to use their own data to produce comparative
      statistics and examine trends over time. Results summarized at the individual
      hospital or aggregate level are being used to stimulate continuous quality
      improvement initiatives. CONCLUSIONS: The HCUP QIs offer a low-cost alternative
      for organizations that have access to administrative data. Current users include
      hospital associations, state health departments, statewide data organizations,
      and individual hospitals. Although the HCUP QIs are intended to serve as
      indicators, not definitive measures, of quality, they were designed to highlight
      quality concerns and to target areas for more intensive study.

PMID- 9547684
TI  - Demanding medical excellence: an interview with Michael Millenson. Interview by
      Louise Kaegi.

PMID- 9547685
TI  - Chromosome 21 detection in human oocyte fluorescence in situ hybridization:
      possible effect of maternal age.
AB  - PURPOSE: The purpose of this study was to evaluate, among 100 uncleaved oocytes,
      the incidence of numerical and structural chromosome 21 and X abnormalities and
      to analyze the influence of various factors, such as in vitro (IVF) indications,
      follicle stimulation protocols, and women's age. METHODS: We investigated 150
      uncleaved oocytes from 128 patients after an IVF attempt. After cytogenetic
      analysis (Giemsa) 100 oocytes (66%) were selected for fluorescence in situ
      hybridization (FISH). Fluorescent probes for human chromosomes X and 21 were used
      simultaneously according to standard procedures for their hybridization and
      detection. RESULTS AND CONCLUSIONS: We analyzed by the FISH protocol 100
      metaphase II oocytes with 22 to 25 chromosomes. Our results demonstrate a high
      rate of disomy for chromosome 21 in human oocytes. Among them, eight were disomic
      (8%) and three were nullosomic (3%) for chromosome 21. Only one disomy of
      chromosome X was noted. The various indications of IVF and the different
      folliculogenesis stimulating protocols did not seem to influence the results but
      suggested a correlation between the maternal age and the aneuploidy rate of
      chromosome 21.

PMID- 9547686
TI  - Low multiple pregnancy rates and reduced frequency of cancellation after
      ovulation induction with gonadotropins, if eventual supernumerary follicles are
      aspirated to prevent polyovulation.
AB  - PURPOSE: Our purpose was to demonstrate the feasibility of the routine aspiration
      of supernumerary follicles in infertile patients with imminent polyovulation
      after ovulation induction with gonadotropins and to examine its effect on the
      frequency of cycle cancellation and on the (multiple) pregnancy rate. METHODS:
      The data on 796 treatment cycles, performed between 1989 and 1996 on 410
      infertile couples, were analyzed retrospectively. From October 1992, whenever
      necessary, supernumerary ovarian follicles were selectively aspirated
      transvaginally under ultrasound guidance to prevent the ovulation of more than
      three follicles. Thereafter, intrauterine insemination was performed. RESULTS:
      After the adoption of transvaginal ultrasound-guided aspiration of supernumerary
      follicles into the treatment protocol in October 1992, the number of canceled
      cycles (P < 0.0001) and the multiple pregnancy rate (P < 0.01) were significantly
      reduced compared to those previously. The overall pregnancy rate remained stable.
      No ovarian hyperstimulation syndrome requiring hospitalization was noted, and no
      complications resulting from the follicle aspiration were registered.
      CONCLUSIONS: Transvaginal ultrasound-guided aspiration of supernumerary ovarian
      follicles increases both the efficacy and the safety of ovulation induction with
      gonadotropins. Because of the limited equipment required, this method represents
      an alternative for conversion of overstimulated cycles to more costly
      alternatives such as in vitro fertilization.

PMID- 9547687
TI  - Isolation and purification of an early pregnancy factor-like molecule from
      culture supernatants obtained from lymphocytes of pregnant women.
AB  - PURPOSE: Our purpose was to determine whether lymphocytes synthesize proteins
      during pregnancy, to observe whether one of the proteins synthesized has early
      pregnancy factor (EPF)-like activity and to isolate and purify this molecule from
      culture supernatants obtained from stimulated lymphocytes of pregnant women.
      METHODS: Lymphocyte proliferation assay and 35S-methionine labeling were done to
      study de novo synthesis of proteins followed by autoradiography to confirm
      synthesis of proteins. The rosette inhibition assay was used for detection of the
      EPF-like molecule. Gel filtration on Sephadex G-100 and RPHPLC were used for
      purification of the EPF-like molecule. RESULTS: The rate of incorporation of 35S
      methionine was significantly higher in the lymphocytes of pregnant women compared
      to those of the control, and autoradiography confirmed the synthesis of proteins
      during pregnancy. There is a total protein enhancement trend observed during the
      first trimester that declines toward term. The EPF-like molecule is observed to
      be synthesized during all the trimesters of pregnancy. This molecule, when
      purified, showed a single homogeneous biologically active peak. CONCLUSIONS: The
      results indicated that there is an enhancement of existing protein or synthesis
      of new proteins during pregnancy. The EPF-like molecule is one of the many
      proteins synthesized and secreted by lymphocytes during pregnancy that, when
      purified, is biologically active.

PMID- 9547688
TI  - Performing testicular or epididymal sperm retrieval prior to the injection of
      hCG.
AB  - PURPOSE: Our purpose was to determine the feasibility and efficacy of performing
      testicular or epididymal sperm retrieval prior to the injection of human
      chorionic gonadotropin (hCG). METHODS: This report deals with 87 sperm-positive
      percutaneous epididymal sperm aspiration (PESA), percutaneous testicular sperm
      aspiration (PTSA), or testicular sperm extraction (TESE) cycles. All sperm
      retrieval procedures were performed prior to administration of hCG to the women.
      Retrieved spermatozoa were cultured in vitro in simple medium for approximately
      40 hr prior to intracytoplasmic sperm injection. RESULTS: In all but one cycle in
      which TESE was performed for nonobstructive azoospermia, motile sperm were
      available for ICSI. The overall fertilization rate was 53%. Pregnancy rate per
      transfer and implantation rate per embryo were 41.2 and 15.7%, respectively.
      CONCLUSIONS: Satisfactory fertilization and pregnancy rates can be achieved when
      PESA, PTSA, or TESE is performed prior to the injection of hCG followed by in
      vitro culture of spermatozoa approximately 40 hr before ICSI. Scheduling of
      testicular or epididymal sperm retrieval cases in this way appears to ease the
      workload on laboratory and operating room personnel. Furthermore, withholding hCG
      when sperm is absent may obviate the unnecessary risk of ovarian hyperstimulation
      when spermatozoa cannot be retrieved.

PMID- 9547689
TI  - Paternal centrosomal dynamics in early human development and infertility.
AB  - PURPOSE: Our purpose was to demonstrate the dynamics of the human sperm
      centrosome during fertilization and cleavage. METHODS: Human gametes, fertilized
      oocytes, and preimplantation embryos were examined by transmission electron
      microscopy. RESULTS: The functional sperm centrosome containing a typical
      centriole (proximal) is inherited at fertilization and forms a sperm monoaster.
      It then replicates and is perpetuated during cleavage. It organizes the mitotic
      apparatus at each stage of cleavage up to the hatching blastocyst stage. Bipolar
      spindles are formed in all monospermic and most dispermic embryos. Occasionally,
      two sperm asters and tripolar spindles are formed in dispermic embryos.
      Centrioles are associated with pronuclei and nuclei at interphases when they
      duplicate and occupy pivotal positions at spindle poles during mitoses. The
      maternal centrosome is not functional. CONCLUSIONS: The human embryo shows
      paternal centrosome inheritance and perpetuation like most other animals.
      Inheritance of defective centrosomes may lead to abnormal cleavage and contribute
      to infertility.

PMID- 9547690
TI  - Preimplantation genetic diagnosis of inherited cancer: familial adenomatous
      polyposis coli.
AB  - PURPOSE: Our purpose was to achieve preimplantation genetic diagnosis (PGD) of
      the dominant cancer predisposition syndrome, familial adenomatous polyposis coli
      (FAPC), as an alternative to prenatal diagnosis. METHODS: The affected patient
      was superovulated and oocytes were retrieved and fertilized by intracytoplasmic
      sperm injection (ICSI). Two cells were biopsied from each embryo and the whole
      genome was amplified by primer extension preamplification (PEP). Nested PCR was
      then used to amplify two APC fragments: one including the APC mutation site and
      the other an informative intragenic polymorphism. Both were detected by
      simultaneous single-strand conformation polymorphism and heteroduplex analysis.
      RESULTS: Four normally fertilized embryos were biopsied on day 3 post ICSI, and
      two cells were successfully removed from each embryo. Following PEP the APC
      mutation was successfully amplified in 7 of 8 cells, and the polymorphism in 6 of
      8 cells. The APC mutation was detected in three embryos. This result was
      confirmed by identification of the mutation associated polymorphism in two cases.
      A single embryo was diagnosed as homozygous normal for the mutation and the
      polymorphism in both cells sampled. This unaffected embryo was transferred to the
      mother, but no pregnancy resulted. CONCLUSIONS: We report here the first
      diagnosis of a cancer predisposition syndrome in human preimplantation embryos.
      Our results indicate that difficulties associated with single-cell PCR, allele
      specific amplification failure in particular, need not prevent preimplantation
      diagnosis of diseases with a dominant mode of inheritance, provided appropriate
      strategies are applied.

PMID- 9547692
TI  - Comparison of the media for isolation and storage of round spermatid nuclei
      before intracytoplasmic injection.
AB  - PURPOSE: This study investigated whether K(+)-rich medium is better than pure
      NaCl solution or Na(+)-rich cell culture medium for handling round spermatid
      nuclei prior to injection into oocytes (ROSNI). METHODS: Round spermatids of the
      mouse were isolated and stored in isotonic NaCl, a cell culture medium (CZB), or
      a nucleus isolation medium (NIM) before injection into oocytes. The rates of
      normal fertilization, embryonic development in vitro, and birth of normal
      offspring after transfer of embryos to foster mothers were determined. RESULTS:
      In vitro development of ROSNI-produced zygotes to blastocysts was the same when
      "naked" spermatid nuclei were exposed briefly to three media. However, a long (60
      min) exposure of the nuclei to Na(+)-rich medium was detrimental. In K(+)-rich
      NIM "naked" spermatid nuclei best retained their ability to participate in normal
      embryonic development. CONCLUSION: NIM was better than Na(+)-rich medium for
      retaining isolated spermatids competent to participate in normal embryonic
      development.

PMID- 9547691
TI  - In vitro stimulation of cumulus-cell expansion by human cord serum in mouse
      oocyte-cumulus complexes.
AB  - PURPOSE: The aim of this study was to test whether human cord serum (HCS)
      containing gonadotropins has an effect on the expansion of oocyte-cumulus
      complexes (OCCs). METHODS: The concentration of follicle stimulating hormone
      (FSH) and luteinizing hormone (LH) was measured in HCS by radioimmunoassay (RIA).
      After short-term culture (4 hr) with or without OCCs, medium containing 0.4%
      bovine serum albumin (BSA) as control or 10% HCS was collected and analyzed for
      its concentration of estradiol, progesterone, and testosterone. RESULTS: The FSH
      concentration was at the basal level, but the LH level was as high as 142.4
      mIU/ml in both natured and denatured serum. Undetectable levels of steroids were
      observed in control media with or without OCCs. In contrast, a moderate amount of
      steroid hormones was detected in culture medium containing HCS. OCCs secreted a
      minute amount of steroid hormones in response to HCS. Similar patterns of cumulus
      expansion were observable by treatment with HCS, human chorionic gonadotropin
      (hCG), or HCS plus hCG after 4, 8, or 22 hr of culture. However, no cumulus
      expansion was observed in controls. CONCLUSION: These results suggest that LH in
      HCS induces cumulus expansion but does not affect the secretion of steroid
      hormones by OCCs during culture.

PMID- 9547693
TI  - Progesterone-activated spermatozoa used for in vitro fertilization.

PMID- 9547694
TI  - An ectopic pregnancy masked by follicular initiation of gonadotropin-releasing
      hormone agonist for pituitary desensitization prior to in vitro fertilization.

PMID- 9547695
TI  - Utilization of Fourier transform-Raman spectroscopy for the study of
      pharmaceutical crystal forms.
AB  - It is well understood that the solid state physical characterization of a drug
      substance is necessary for successful development and approval of a
      pharmaceutical product AAPS [1]. Physical analytical techniques used include:
      XRD, IR, DSC, TG, and NMR. Recently, Fourier transform (FT) Raman spectroscopy
      has become a more common technique. Complimentary to IR, FT-Raman can be used to
      differentiate between different crystal forms of a drug substance. FT-Raman
      exhibits several advantages over IR and the other physical analytical techniques.
      Very little sample is required with no preparation (dilution), analysis time is
      quick, and since water is a weak scatter (Raman spectrum of water contains three
      low intensity peaks), crystallization studies of drug substances from aqueous
      solutions can be performed. Additionally, through the use of a variable
      temperature accessory, phase diagrams can be determined for crystal systems,
      leading to further characterization of those systems. This paper introduces the
      use of FT-Raman spectroscopy for pharmaceutical development activities. Specific
      examples will be shown for investigations of crystal forms (qualitative and
      quantitative) and crystallization studies.

PMID- 9547696
TI  - Development of a simple spectrophotometric method for propylene glycol detection
      in tablets.
AB  - A simple spectrophotometric procedure was developed and validated to indirectly
      assess the quantities of propylene glycol (PG) remaining in compressed
      liquid/powder admixtures. Such simplified quantitation may facilitate several
      testing procedures related to various aspects of formulation development and
      material testing of pharmaceutical powder excipients using various nonvolatile
      liquids as the diluents. In the present study, this new and simple approach for
      PG quantitation was developed as an integral part of a new method termed the
      liquisolid compressibility (LSC) test, used to characterize the compaction
      behavior of powder excipients. According to LSC testing, several admixtures of a
      nonvolatile liquid (in this case PG) and a powder, differing in their PG/powder
      weight ratio, are compressed in order to assess their compactabilities. The PG
      content of such compacts may then be directly quantitated by the USP gas
      chromatographic method or, indirectly, by this new simple spectrophotometric
      procedure. The new approach involves the addition of a dye marker to the PG prior
      to its incorporation into the powder. After compression, the PG amount remaining
      in the compacts may be determined by simply extracting the dye from the tablets
      and analyzing the extracts spectrophotometrically. In this manner, the dye
      content thus obtained may be extrapolated to the respective net amount of PG
      originally added as a dye/PG solution to the powder. Statistical comparison of
      the results obtained from both methods revealed almost absolute correlation.

PMID- 9547697
TI  - Capillary gas chromatographic assay of residual methenamine hippurate in
      equipment cleaning validation swabs.
AB  - A capillary gas chromatographic method is described for the determination of
      methenamine hippurate residue in swabs collected from manufacturing equipment
      surfaces. Any residual methenamine hippurate remaining on process equipment after
      cleaning is removed by swabbing with one wet polyester Absorbond swab (4" x 4")
      pre-moistened with water followed by a dry Absorbond swab. The residual
      methenamine hippurate is chromatographed on a 30 x 0.32 mm (i.d.) Supelcowax-10
      capillary column of 0.25-micron film thickness. The amount of residual
      methenamine hippurate is determined by comparing the ratio of methenamine
      hippurate peak area response to that of p-cresol (internal standard) obtained for
      the sample to a linear calibration curve obtained for a series of standard
      solutions. The method is demonstrated to be sufficiently linear, accurate,
      precise, sensitive and rugged for the determination of low levels of methenamine
      hippurate on equipment surfaces. Using this method, the mean recovery of
      methenamine hippurate from spiked Absorbond swab samples contained in high
      density polyethylene bottles was 105.2%, with a relative standard deviation (RSD)
      of +/- 7.1% (n = 25). The mean recoveries of methenamine hippurate from spiked
      test plates for '180 Grit' Stainless Steel, Teflon and WARCO White (neoprene and
      PVC) gasket material were 77.2, 96.1 and 50.6%, with RSDs of +/- 9.4 (n = 25), +/
      4.3 (n = 25) and +/- 36% (n = 20), respectively. Recovery correction factors
      have been incorporated into the method. The method was successfully applied to
      the assay of actual equipment cleaning validation swab samples. Stability studies
      demonstrate that methenamine hippurate is not very stable on the equipment
      surfaces or in the swabs. It is recommended that the surfaces be swabbed
      immediately after cleaning and the swabs analyzed within 24 h after sample
      collection. The results demonstrate that in order to fully validate the cleaning
      procedures, it is not only necessary to investigate the recovery of the drug from
      equipment surfaces and swabs but also that the stability of the drug on the
      surfaces and swabs be determined.

PMID- 9547698
TI  - Evaluation of microdialysis sampling of aqueous humor for in vivo models of
      ocular absorption and disposition.
AB  - The dynamics of beta-adrenergic-associated reductions in aqueous humor production
      for treatment of elevated intraocular pressure are not well understood. In
      particular, the relationship between ocular pharmacokinetics and pharmacodynamics
      has yet to be established. This study was undertaken to develop a procedure for
      examining the ocular absorption and disposition of topically administered
      ophthalmic beta-adrenergic antagonists in individual animals. Dogs were
      anesthetized with isoflurane and a microdialysis probe was implanted in the
      anterior chamber of one eye and perfused with 0.9% saline at a rate of 2
      microliters min-1. 3H-propranolol was administered by intracameral injection or
      topically. Each dog received intracameral and topical propranolol, in alternate
      eyes on separate days, in a randomized cross-over fashion. Microdialysis probe
      effluent was collected every 5 min for > or = 2.5 h; concentrations of
      propranolol were determined by liquid scintillation spectroscopy and were
      corrected for probe recovery of the substrate as determined by in vivo
      retrodialysis (approximately 46%) to estimate aqueous humor concentrations. In
      separate experiments in rabbits, microdialysis probes were implanted in each eye.
      3H-propranolol was administered topically to one eye; the contralateral eye
      received intracameral 3H-propranolol. Model-independent pharmacokinetic
      parameters for each treatment phase were calculated. The mean +/- S.D. times to
      peak concentration of propranolol in aqueous humor were 86.6 +/- 47.6 min in the
      dog and 54.1 +/- 20.4 min in the rabbit. The terminal rate constant was 0.0189 +/
      0.00429 min-1 in the dog vs. 0.00983 +/- 0.00546 min-1 in the rabbit.
      Intraocular tissue availability of propranolol differed markedly between the dog
      (n = 3) and rabbit (n = 3) (approximately 0.056 in the dog vs. approximately 0.55
      in the rabbit). These results demonstrate the utility of microdialysis sampling
      for examination of ocular pharmacokinetics.

PMID- 9547699
TI  - Sensitive determination of erythromycin in human plasma by LC-MS/MS.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the
      analysis of erythromycin in human plasma (EDTA as anticoagulant) was developed
      and validated. The concentration ranges were 0.5-50 and 50-5000 ng ml-1. The
      procedure involved alkalization of 0.5 ml of plasma, one step liquid-liquid
      extraction, dryness of the extract and reconstitution in 80:20
      water:acetonitrile. An Inertsil ODS-2 5 microns, 3.0 x 50 mm column (Metachem)
      with a C8 guard column and isocratic mobile phase were used for liquid
      chromatography. The mobile phase consisted of 1:1 acetonitrile:water with 2 mM
      NH4OAc and 0.1% HOAc. A flow rate of 0.7 ml min-1 was used. The analysis time on
      LC-MS/MS for one sample was approximately 2 min. A Turbo-Ionspray source was
      interfaced between the HPLC and triple quadrupole mass spectrometer (Sciex API
      III Plus). MS/MS analysis used Multi-Reaction Monitoring (MRM) mode. The lowest
      limit of quantitation (LOQ) was 0.5 ng ml-1 with all Quality Control (QC) sample
      recoveries varying between 88 and 105%. Nine intraday and interday calibration
      curves were generated yielding correlation coefficients ranging from 0.995 to
      1.000. Average recovery for erythromycin at 1 ng ml-1 was 105% (+/- 4.5%).
      Average recovery for the internal standard was 83-103%. Short-term and long-term
      stability in the freezer (-20 degrees C), bench stability, and stability after 3
      freeze/thaw cycles at -20 and -80 degrees C were conducted. The samples were
      found to be stable under all conditions. The method developed and validated
      proved useful for clinical pharmacokinetic study sample analysis with high
      throughput due to its high sensitivity and very short analysis time.

PMID- 9547701
TI  - Validation of an LC-MS assay for the quantification of the enantiomers of Org
      4428 in human plasma.
AB  - A sensitive and selective liquid chromatographic mass spectrometric assay has
      been validated for the quantification of Org 4428 enantiomers in human plasma.
      The assay employs n-hexane extraction from alkalinized plasma, separation on a
      narrow-bore enantioselective normal phase Chiralpak AD column and APCI MS-MS
      detection. The lower limit of quantification is 0.5 ng ml-1 plasma for the
      individual enantiomers.

PMID- 9547700
TI  - High-performance liquid chromatography-mass spectrometry-mass spectrometry
      analysis of morphine and morphine metabolites and its application to a
      pharmacokinetic study in male Sprague-Dawley rats.
AB  - A high-performance liquid chromatography tandem mass spectrometry-mass
      spectrometry (LC-MS-MS) assay was developed for the analyses of morphine,
      morphine glucuronides and normorphine in plasma samples from rats. The analytes
      were extracted by using C2 solid-phase extraction cartridges. The extraction
      recoveries were 100% for morphine, 84% for morphine-3-glucuronide, 64% for
      morphine-6-glucuronide and 88% for normorphine. Both intra- and inter-assay
      variabilities were below 11%. Using a plasma sample size of 100 microliters, the
      limits of detection were 13 nmol l-1 (3.8 ng ml-1) for morphine, 12 nmol l-1 (5.5
      ng ml-1) for morphine-3-glucuronide, 26 nmol l-1 (12 ng ml-1) for morphine-6
      glucuronide and 18 nmol l-1 (5.0 ng ml-1) for normorphine, at a signal-to-noise
      ratio of 3. The present assay was applied to a pharmacokinetic study in rats
      after intraperitoneal administration of morphine.

PMID- 9547702
TI  - Identification and determination of phase I metabolites of propafenone in rat
      liver perfusate.
AB  - Propafenone (PF) is a class 1C antiarrhythmic agent. To study the mechanisms of
      PF interactions with dietary nutrients in isolated, perfused rat livers,
      metabolites of PF in liver perfusate were identified and an analytical method was
      developed for these metabolites plus parent drug. Identification of phase I
      metabolites was performed using HPLC/MS equipped with a Lichrospher RP-18 column
      and tandem mass spectrometry (MS/MS) with electrospray and atmospheric pressure
      chemical ionizations. Three major metabolite peaks, whose protonated molecular
      ions were m/z 358, 358 and 300, were identified as a propafenone derivative
      hydroxylated in the omega-phenyl ring (omega-OH-PF), 5-hydroxypropafenone (5-OH
      PF), and N-despropylpropafenone (N-des-PF). The levels of omega-OH-PF, 5-OH-PF, N
      des-PF and PF were determined simultaneously by HPLC with UV detection at 210 nm
      and a mobile phase of 0.03% triethylamine and 0.05% phosphoric acid in water
      acetonitrile-methanol (45:20:35, v/v/v) after extraction with 5 ml diethyl ether
      at pH 10.0 and evaporation of solvent under nitrogen. The results revealed that
      omega-OH-PF, which was not found in humans, was the major metabolite of PF in rat
      liver perfusate, not 5-OH-PF which is the major metabolite in human plasma.

PMID- 9547703
TI  - Rapid and sensitive high performance liquid chromatographic method for the
      determination of itraconazole and its hydroxy-metabolite in human serum.
AB  - Published high performance liquid chromatographic (HPLC) methods for the
      determination of itraconazole (ITZ) in biological matrices are labor intensive,
      extraction-based procedures which operate at a pH approaching the limit of column
      tolerance, and unless modified, cannot measure its hydroxy-metabolite (OH-ITZ). A
      protein precipitation-based method requiring no solvent extraction and utilizing
      a base-deactivated C18 analytical column to minimize peak tailing is described
      herein. Calibration curves for OH-ITZ and ITZ were linear from 25-1500 ng ml-1
      (r2 > or = 0.999). Intra-assay relative standard deviations (R.S.D.) were below
      12%. Inter-assay R.S.D. were below 14%. This method provides a rapid means for
      the accurate and precise determination of both OH-ITZ and ITZ concentrations in
      human serum.

PMID- 9547704
TI  - A HPLC method for the determination of 9-cis retinoic acid (ALRT1057) and its 4
      oxo metabolite in human plasma.
AB  - A HPLC method was developed and validated for the quantitation of 9-cis-retinoic
      acid (ALRT1057) and its major metabolite, 4-oxo-9-cis-retinoic acid (LG100182) in
      human plasma. Samples were buffered and extracted with methyl-tert-butyl-ether.
      The analytes and an I.S. were separated on a C18 HPLC column using a shallow
      gradient of 70-89% organic solvent. The analytes were quantitated by UV detection
      at 348 nm. Selectivity against endogenous compounds and potential metabolites
      (retinol, all trans-, 13-cis-, and 4-hydroxy-9-cis-retinoic acid) was
      demonstrated. The run time was 29 min. The standard curve was linear from 2.5 to
      450 ng ml-1. Interassay precision for both analytes in quality control samples
      was less than 5.0% RSD. Accuracy was within 11.0% RE for both compounds. Analyte
      stability during sample storage, extraction processing, and chromatography was
      established. Method ruggedness was tested by two analysts and on two HPLC
      systems. This method has been applied to the quantitation of clinical samples.

PMID- 9547705
TI  - Determination of methazolamide concentrations in human biological fluids using
      high performance liquid chromatography.
AB  - Methazolamide is a carbonic anhydrase inhibitor used to treat glaucoma. In vivo,
      methazolamide readily distributes into red blood cells. Therefore, both blood and
      plasma concentration data are needed in order to characterize the
      pharmacokinetics of methazolamide. In the present study, an analytical method
      using high performance liquid chromatography was validated for determination of
      methazolamide concentrations in several biological fluids. Through slight
      modification of a previously reported method for acetazolamide, another carbonic
      anhydrase inhibitor, methazolamide was readily quantitated in whole blood, plasma
      and urine. Sample preparation involved liquid-liquid extraction with ethyl
      acetate followed by a washing step using phosphate buffer (pH 8.0). After back
      extraction into glycine buffer (pH 10.0), samples were then washed with ether and
      injected onto the chromatograph. Chromatography was performed using a C-18, 5
      microns reverse-phase column with UV detection at a wavelength of 285 nm. Mobile
      phase consisted of 0.05 M sodium acetate (pH 4.0) and acetonitrile (20%). The
      assay was validated over two standard concentration ranges from 1 to 100
      micrograms ml-1, concentrations reflective of those expected in vivo, Calibration
      curves were linear for all biological fluids and coefficients of variation for
      interday and intraday reproducibility studies were less than 8% (range 3.1-7.9%).
      The method was used to measure methazolamide concentrations in blood, plasma and
      urine following oral administration to five human subjects.

PMID- 9547706
TI  - Simplified reversed-phase HPLC method with spectrophotometric detection for the
      assay of verapamil in rat plasma.
AB  - A high-performance liquid chromatographic (HPLC) method was developed for the
      assay of verapamil in rat plasma. After deproteinization of the plasma sample
      with an acetonitrile-perchloric acid (8:2) mixture containing dextromethorphan,
      the internal standard, an aliquot of the supernatant was directly analyzed on a
      cyanopropylsilane column with methanol-acetonitrile-triethylamine acetate buffer
      (10:30:60) as the mobile phase and detection at 235 mm. At a flow rate of 1.5 ml
      min-1, a complete analysis was completed in less than 6 min. The method was
      linear for verapamil concentrations in the range 0.5-10 micrograms ml-1 (r =
      0.9999). Recoveries for the same drug concentrations from spiked rat plasma
      ranged from 85.6-93.0% (n = 8). The mean RSD values for intraday and interday
      assay reproducibility (n = 3) were, in both cases, less than 0.9%. The limit of
      detectability was about 0.1 microgram ml-1. The method was found useful to
      monitor the plasma levels of verapamil in rats that had received this drug by the
      nasal, oral and intravenous routes of administration.

PMID- 9547707
TI  - A simplified chromatographic method for quantitative determination of coenzyme
      Q10 in dog plasma.

PMID- 9547708
TI  - A sensitive assay of metoprolol and its major metabolite alpha-hydroxy metoprolol
      in human plasma and determination of dextromethorphan and its metabolite
      dextrorphan in urine with high performance liquid chromatography and fluorometric
      detection.
AB  - A reverse-phase High Performance Liquid Chromatographic (HPLC) method was
      developed for the analysis of metoprolol in the large number of human plasma
      samples obtained in in vitro-in vivo correlations (IVIVC) and bioavailability
      studies of extended release formulations of metoprolol tartrate. The metabolite,
      alpha-hydroxy metoprolol (OH-met), could also be quantified. The analytes were
      extracted from the plasma using solid phase columns, separated on a C-4
      analytical column followed by fluorimetric detection. The linearity, precision,
      accuracy, stability, selectivity and ruggedness were validated for the
      concentration ranges of 1-400 ng ml-1 for metoprolol and 0.5-200 ng ml-1 for OH
      met. The same chromatographic conditions were slightly modified to quantify
      dextromethorphan and its metabolite dextrorphan in urine in the concentration
      range 0.052-0.05 microgram ml-1 as a method for screening for fast metabolizers.

PMID- 9547709
TI  - Determination of famotidine in human plasma by high performance liquid
      chromatography with column switching.
AB  - A rapid, sensitive and robust reverse-phase high performance liquid
      chromatographic (HPLC) method with column switching and an internal standard for
      the quantitative determination of famotidine in human plasma is described.
      Famotidine and the internal standard were isolated from plasma samples by cation
      exchange solid phase extraction with SCX cartridges. The chromatographic
      separation was accomplished by an Inertsil C4 column with a mobile phase of
      acetonitrile/phosphate aqueous solution, connected by a switching valve to a BDS
      Hypersil C8 column with a mobile phase of acetonitrile/sodium dodecyl sulfate and
      phosphate aqueous solution. UV detection was set at 267 nm. The standard curve
      was linear in the concentration range of 1-100 ng ml-1. The intraday coefficients
      of variation at all concentration levels were less than 10%. The interday
      consistency was assessed by running QC samples during each daily run. The limit
      of quantification for famotidine in human plasma was 1 ng ml-1. The method has
      been utilized to support clinical pharmacokinetic studies in healthy volunteers
      who received famotidine 10 mg orally.

PMID- 9547710
TI  - Determination of blood sugars by high pressure liquid chromatography with
      fluorescent detection.
AB  - In this study, a high pressure liquid chromatography method with fluorescent
      detector was developed to analyze blood galactose, lactose and glucose
      simultaneously. Plasma sugars were prepared as fluorescent derivatives to react
      with FMOC-hydrazine (9-fluorenyl methyl chloroformate). A C18 reversed phase
      column and a fluorescent detector were used and run in ambient. The resolution
      index of galactose and glucose derivatives in the analytical method was 1.15. The
      coefficients of variation of the analysis were less than 7.5%. The concentration
      of FMOC-hydrazine did not significantly influence the analytical results for
      determination of the concentration of galactose. However, the ratios of
      acetonitrile in the mobile phase significantly affected the analysis of the
      fluorescent derivatives of sugars. The sensitivity of this method for galactose
      detection was 5 micrograms ml-1, and the required plasma volume for testing was
      only 25 microliters each. This analytical method was successfully applied to
      study the pharmacokinetics of galactose in vivo in a rabbit model.

PMID- 9547711
TI  - A rapid and simple assay to determine the blood and urine concentrations of 1-(5
      [123/125I]iodo-5-deoxyarabinofuranosyl)-2-nitroimidazole, a hypoxic cell marker.
AB  - Pharmacokinetic and dosimetric parameters of the hypoxic tissue imaging agent
      iodoazomycin arabinoside (123I-IAZA) have been investigated in human volunteers.
      In conjunction with this study it was necessary to develop an assay for low
      levels of the radiolabelled compound in blood and urine. A combination of high
      performance liquid chromatography (HPLC) and gamma counting produced a highly
      selective, sensitive and rapid assay for the analysis of 123/125I-IAZA in human
      and animal blood and urine samples. Conventional HPLC assays for the tracer
      quantities of this radioactive agent in blood have not been reported previously.
      The addition of non-radiolabelled IAZA to the blood and urine samples containing
      radiolabelled IAZA allowed the pharmaceutical to serve as its own internal
      standard. This reverse isotope dilution approach permitted identification of the
      appropriate HPLC peak by UV detection, followed by highly sensitive
      quantification of the radiolabelled species by gamma counting. Blood samples were
      prepared for HPLC by a solid-phase extraction without the loss of IAZA from
      serum, with an extraction efficiency of 99.7 +/- 7.1% from human serum. Urine
      samples could be analyzed directly by HPLC, without the solid-phase extraction
      step. The detection limit in biological fluids depends on the specific activity
      of radiolabelled 123/125I-IAZA. In this study it was possible to detect serum
      concentrations of 123I-IAZA as low as 7.46 pg (21 fmol) per ml. The radiometric
      detection limit for 123I-IAZA in this assay was 10.8 Bq ml-1 of serum.

PMID- 9547712
TI  - Validation of an HPLC method for the determination of CP-93,393 in CP-93,393-1
      tablets.
AB  - A reversed-phase high performance liquid chromatographic (HPLC) assay developed
      for the CP-93,393-1 drug substance was adapted for use with CP-93,393-1 tablets.
      Using a novel experimental matrix, validation was performed to obtain linearity,
      reproducibility and recovery and to meet current regulatory requirements.
      Deviations in the sample preparation procedure were performed to demonstrate the
      ruggedness of the assay.

PMID- 9547713
TI  - Determination of trace levels of hydrazine in the penultimate intermediate of a
      novel anti-infective agent.

PMID- 9547714
TI  - Determination of aspartame and its degradation and epimerization products by
      capillary electrophoresis.
AB  - Two capillary zone electrophoretic assays using run buffers of pH 9.35 and pH
      2.70 have been developed for the determination of aspartame (alpha-L-Asp-L
      PheOMe) and its potential degradation products including Phe, PheOMe, 5-benzyl
      3,6-dioxo-2-piperazineacetic acid (DKP), the dipeptides Asp-Phe and Phe-Asp, as
      well as the isomeric beta-aspartame (beta-L-Asp-L-PheOMe). As an uncharged
      species at pH 2.7 DKP could not be determined. Between pH 2.0 and 3.5 the
      resolution of the diastereomers of aspartame and beta-aspartame was investigated.
      While the resolution of the epimeric beta-isomers exhibited a plateau between pH
      2.3 and 2.7, resolution of the aspartame diastereomers peaked at pH 3.0. Using
      salicylic acid and Phe-Gly as internal standards at pH 9.35 and 2.70,
      respectively, linear calibration curves were obtained for a concentration range
      between 5 micrograms ml-1 and 1 mg ml-1. The R.S.D. for intraday and interday
      analysis ranged from 1.0 to 3.6% and 1.5% to 9.1%, respectively. The capillary
      electrophoresis assays were applied to analyze aspartame solutions heated to 70
      degrees C. In agreement with the literature data aspartame was found to be less
      stable at pH 7 compared to pH 3. In contrast to aspartame itself, an approximate
      20% epimerization of beta-aspartame was observed in the incubation mixtures.

PMID- 9547715
TI  - The application of capillary electrophoresis for monitoring effects of excipients
      on protein conformation.
AB  - Studies were conducted to assess the utility of free solution capillary
      electrophoresis (CE) for monitoring the effects of selected excipients on the
      thermal denaturation of a model protein (Ribonuclease A, RNase A) at low pH.
      Thermal denaturation/unfolding experiments were conducted via temperature
      controlled CE using a run buffer of 20 mM citric acid in the pH range of 2.3-3.1,
      with a marker peptide incorporated to correct for temperature-induced changes in
      endoosmotic flow. The effects of selected excipients on the thermal unfolding of
      RNase A were then evaluated by adding either sorbitol, sucrose, polyethylene
      glycol 400 (PEG 400) or 2-methyl-2,4-pentanediol (MPD) to the electrophoretic run
      buffer (pH 2.3). Confirmatory denaturation experiments were conducted under the
      same solution conditions using circular dichroism (CD) spectropolarimetry. Using
      temperature-controlled CE, an increase in solution pH from 2.3 to 2.7 and 3.1
      resulted in an increase in transition temperatures of RNase A by approximately 8
      and 13 degrees C, respectively. Similar shifts in transition temperatures were
      observed when thermal denaturation transitions were monitored by far-UV CD.
      Sorbitol (0.55-1.1 M) and sucrose (0.55 M) each shifted the denaturation
      transition temperatures of RNase A to higher values, whereas PEG 400 and MPD had
      minimal effect on the unfolding transition midpoint at the concentrations
      evaluated (0.55 M for each). The observed changes in the transition temperatures
      for RNase A as a function of pH and selected excipients were similar when
      measured by either CE or far-UV CD. These results support the utility of CE for
      monitoring the effects of neutral excipients on the thermal denaturation of a
      model protein under selected conditions. The widespread utility of the technique
      may be limited by the narrow temperature range of most commercial CE instruments
      and the need to use extreme pH conditions to monitor the complete denaturation
      transition.

PMID- 9547716
TI  - Bioanalytical calibration curves: variability of optimal powers between and
      within analytical methods.
AB  - The objective of this study was to investigate the variability of optimal power
      models in contrast to common regression models within and between analytical
      methods, as well as the frequency of outlier rejection. This was done by fitting
      the power model to calibration curve data using the minimum sum of squared
      residuals as a curve selection criterion. The jackknife percent deviation was
      used for detecting outliers. The data were obtained from 2087 analytical batches
      for 91 projects using various analytical techniques. The most frequent regression
      model varied between analytical techniques while the median and interquartile
      range of the optimal powers were stable. Outlier rejection is highest in GC and
      LCMS in which the Wagner (Quadratic, log-log) is the most frequent model. These
      results suggest that the greatest source of variability in the ideal
      transformation may not be the analytical technique but other within-lab sources.
      Outlying values may be due to these other sources of variability as suggested by
      the outlier rejection profile.

PMID- 9547717
TI  - Bioanalytical calibration curves: proposal for statistical criteria.
AB  - Curve fitting procedures for bioanalytical assays are based on classical linear
      least squares (LSE) theory. A common procedure is to select among various models
      and weighting factors using the R2 as a goodness-of-fit criterion. It is
      questionable whether R2 is the most appropriate criterion for model selection.
      This is compounded by an often subjective removal of outliers. In this article,
      statistical curve fitting and diagnostic criteria are proposed. The fitting
      procedure is a Box-Cox-type power transformation of the data. The optimal
      transformation is obtained as the one that minimises the sum of squared
      deviations. Potential outlying standards are screened during the diagnostics
      stage as those whose jackknife percent deviations exceed 20%. The main advantage
      of this method is that it is objective and uniformly applicable across analytical
      techniques. Furthermore, the optimal transformation obtained in this way is
      unique. The results are demonstrated by comparing the power model to the R2
      approach through the statistical analysis of 2094 analytical batches for 91
      projects using various analytical techniques, namely GC, HPLC, LCMS and GCMS. The
      results indicate that the power model is robust and that QC batch acceptance
      using the power model is at least as good as the current method. These results
      hold true across all analytical techniques. It is thus strongly suggested that
      curve fitting and standard outlier detection for bioanalytical assays should be
      based on a power model and on jackknife percent deviations method with acceptable
      cut-off values.

PMID- 9547718
TI  - [Mortality inequalities according to education in the city of Barcelona].
AB  - BACKGROUND: In Spain, individual-based studies on inequalities in mortality are
      scarce by the fact that death certificate often do not complete information on
      occupation. This study describes socio-economic inequalities in mortality using
      as social indicator the level of education, because in Barcelona the mortality
      registry is linked with the municipal census. MATERIAL AND METHODS: 28,046
      residents in Barcelona, Spain, 24 years and older who died in 1992 and 1993 were
      studied. The level of education of the deceased people was obtained from the
      municipal census. Age standardized mortality rates were calculated by each
      educational level by sex. The most important causes of death were studied.
      Poisson regression models were adjusted to obtain the mortality ratio among the
      educational levels (being the more educated the reference group). RESULTS: The
      mortality ratio by all causes in illiterate was 2.05 times higher in males (p <
      0.001) and 1.62 in females (p < 0.001). The higher was the education level, the
      lower were the rates. This mortality pattern was observed in the majority of
      causes of death studied and mainly in AIDS, cirrhosis and drug overdose, also in
      lung cancer in males and coronary disease in females. Breast and lung cancer in
      females were higher in the more educated. Educational inequalities by age group
      were more important in the youngest people and diminished with increasing age.
      CONCLUSION: This results show the existence in Barcelona, Spain, of inequalities
      in mortality by education level in the main causes of death in males and females
      and in the majority of age groups.

PMID- 9547721
TI  - [Mortality and little education].

PMID- 9547719
TI  - [Prevalence of human immunodeficiency virus type 1 and Mycobacterium tuberculosis
      infections in a prison population in the years 1989 to 1995].
AB  - BACKGROUND: This study was carried out to know the prevalence of human
      immunodeficiency virus type 1 (HIV-1) and Mycobacterium tuberculosis infection in
      a penitentiary center, the risk factors and the prevention measures to reduce
      this infection. SUBJECTS AND METHODS: 1,173 men from a penitentiary center
      between 1989-1995 were included. Demographic data, risk factors and penitentiary
      variables were studied. Antibodies against HIV were found and confirmed using
      Western blot; tuberculin skin reaction (PPD) and CD4 lymphocyte cant were
      studied. RESULTS: The mean age was 31.8 (SD 8.8 years). They were 61.5% Spanish
      people and 48.1% were in prison for second time. The 49.7% used illegal drugs.
      Overall prevalence of HIV-1 infection was 24.3%. The differences of percentages
      for HIV-1 infection in intravenous drug users (IVDU) were 67.7% and in non IVDU
      were 3.8% with a significant statistical difference (chi 2 = 557.5; p < 0.0001).
      Using a multivariate test (stepwise method) we found that the probability to be
      HIV-1 positive in a penitentiary center was 21.9 times higher in IVDU, 5.6 times
      in Spanish prisoners, 2.6 times in subjects with more than one prison stay and
      1.7 times if they had tatoos. The global prevalence of tuberculosis infection
      (PPD positive) was a 43.8%, and was associated to the second time inmates in this
      penitentiary center (chi 2 = 22.1; p < 0.001). A 54.4% of HIV-1 positive people
      showed a CD4 T lymphocyte count > or = 500 x 10(6)/l. CONCLUSIONS: We found a
      high prevalence of HIV-1 and tuberculosis infection and drug use in this
      penitentiary center. HIV-1 was transmitted and related by sharing syringes
      between IVDU independent of the stay in prison. The diagnosis of HIV-1 infection
      was made soon. The treatments of drug users in penitentiary centers and programs
      for lowering the risk are very important.

PMID- 9547720
TI  - [Defects of adrenal steroidogenesis in patients with hirsutism].
AB  - BACKGROUND: To determine the frequency and the type of adrenal steroidogenic
      abnormalities in hirsute women. SUBJECTS AND METHODS: ACTH test was performed
      during follicular phase in 127 hirsute and 40 normal (control) women. Before ACTH
      injection we measured in serum by RIA: 17-OH-pregnenolone (17-OH-P5), 17-OH
      progesterone (17-OH-P4), androstenedione (AN), cortisol (CT), 11-deoxycortisol
      (DCT), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), total (TT) and
      free (FT) testosterone, oestradiol (E2), progesterone (PR), androstenediol
      glucuronide (AG), LH, FSH and prolactin. After 60 min of ACTH injection 17-OH-P5,
      17-OH-P4, AN, DHEA, CT and DCT were measured. Net increment of stimulated
      steroids and the ratios 17-OH-P5/17-OH-P4, DHEA/AN, 17-OH-P4/CT, 17-OH-P5/CT and
      DCT/CT were calculated. Pelvic ultrasonographic exploration was done when
      irregular menses were reported. RESULTS: Up to 31% of the patients presented
      enzymatic defects in adrenal steroidogenesis. Diagnostic criteria for enzyme
      defects were established. Late-onset 21-hydroxylase deficiency was diagnosed in 6
      (4.5%) patients, HLA typing of these patients demonstrated that 4 out of 6 had
      B14-DR1. Sixteen women (12.6%) displayed a 17-OH-P4 response and the net
      increment 2 SD above the normal mean concentration, which are diagnostic criteria
      for late-onset 21-hydroxylase deficiency carriers. We diagnosed a 3 beta
      hydroxysteroid dehydrogenase defect when 17-OH-P5 and DHEA responses, their net
      increment and the 17-OH-P5/17-OH-P4 and 17-OH-P5/CT ratios were 2 SD above the
      normal mean after ACTH: 14 women were diagnosed. 11 beta-hydroxylase deficiency
      diagnosis was made when DCT response, its net increment and the DCT/CT ratio
      after ACTH were 2 SD above the normal mean: 7 women were detected. Associated
      biosynthetic defects were described. CONCLUSIONS: One third of our patients with
      hirsutism presented anomalous response to ACTH, consistent with enzymatic
      abnormalities in adrenal steroidogenesis.

PMID- 9547722
TI  - [Glucose intolerance: the fragile threshold of diabetes mellitus].

PMID- 9547723
TI  - [Atypical familial microcytosis: a familial and genetic study].
AB  - The characteristics of familiar atypical microcytosis studied during one year
      were evaluated. Out of 149 patients with microcytosis in whom iron deficiency was
      ruled out, a heterogenous beta-thalassemia was diagnosed in 72 cases, a
      heterozygous delta beta-thalassemia in 16 cases and a hemoglobinopathy in 3
      cases. The microcytosis was related to an inflammatory anemia in 12 cases and to
      an hemopathy in 9 cases. An atypical microcytosis was detected in 37 patients. A
      familiar and molecular analysis was carried out to detect alpha-thalassemia in
      cases with atypical microcytosis. It was possible to complete the familiar and
      molecular analysis in 35 out of 37 cases, and an alpha-thalassemia was observed
      in 31 patients. Most cases proved to be heterozygous or homozygous-alpha 3.7
      thalassemia. No patient with heterozygous alpha zero-thalassemia was found. Most
      cases of familiar atypical microcytosis in our country are due to -alpha 3.7
      thalassemia. Bearing these findings in mind, this analysis should only be used in
      situations where a problem of prenatal diagnosis is present. Moreover, systematic
      molecular analysis of familiar atypical microcytosis could be justified if the
      MCV is lower than 75 fl.

PMID- 9547724
TI  - [AIDS: ethical and legal problems of physician-patient relations in the light of
      the new penal code].

PMID- 9547725
TI  - [Value of differences among patients in comparative trials].

PMID- 9547726
TI  - [Who wants to be the chief?].

PMID- 9547727
TI  - [Actol and acfol: drugs that won't be confused anymore].

PMID- 9547728
TI  - [Hereditary cancer of the breast and ovary].

PMID- 9547729
TI  - [Computer technology applied to hospitalized patients].

PMID- 9547730
TI  - [Prevalence of bacterial vaginosis in an obstetric population of Barcelona].
AB  - OBJECTIVES: To investigate the prevalence and risk factors of bacterial vaginosis
      (BV) in a pregnant population of Barcelona (Spain). MATERIAL AND METHODS: 301
      pregnant women controlled in the Hospital Clinic i Provincial (HCP) of Barcelona
      were enrolled in the study. Complete epidemiological information, and vaginal
      samples were available in 293 women. BV was diagnosed by Gram stain of vaginal
      smear (Nugent's criteria). RESULTS: BV was detected in 22 pregnant women (7.5%;
      95% CI: 4.6-10.5%). There was no association between race, parity, education,
      marital status, smoking and drug use, and the presence of BV. Non-use of birth
      control method (72.3% vs 34.4%; p < 0.0001), presence of sexually transmitted
      diseases (STD) during pregnancy (22.7% vs 3.7%; p < 0.0001), HIV seropositivity
      (13.6% vs 2.9%; p = 0.041) and presence of symptoms of vaginitis (40.9% vs 13.3%;
      p = 0.009) were significantly associated with the presence of BV. CONCLUSIONS:
      The prevalence of BV in a pregnant population of Barcelona (Spain) is 7.5%.
      Further work is needed to evaluate the usefulness of BV as a prescreening marker
      for STD and HIV infection. The Gram stain provides an inexpensive, fast and easy
      method to diagnose BV, and may allow us to screen, treat and prevent the
      morbidity and mortality associated with it.

PMID- 9547731
TI  - [Incidence and risk factors of the association of AIDS and tuberculosis in
      Spain].
AB  - BACKGROUND: Incidence of tuberculosis in persons coinfected with HIV is very
      high. The aim of this study was to determine the risk factors for tuberculosis in
      AIDS patients in Spain. PATIENTS AND METHODS: A study was carried into AIDS cases
      (1993 European AIDS case definition) over 12 years old, diagnosed in Spain in
      1994. A comparison was run between cases with tuberculosis and the remaining
      reported AIDS cases on the register, by sex, age, transmission category and
      prison record. Multiple logistic regression was used to assess the independent
      effect of each variable, with the adjusted odds ratio (ORa) and their 95%
      confidence intervals. RESULTS: Annual incidence of AIDS and tuberculosis
      comorbidity was 8.9 per 100,000 inhabitants. Multivariate analysis revealed that
      tuberculosis in AIDS patients appeared with higher frequency in: males (ORa =
      1.4; CI 95%, 1.3-1.6); the 13-29 age group (ORa = 1.3; CI 95%, 1.1-1.5) and the
      30-39 year old group (ORa = 1.1; CI 95%, 1.0-1.3), injecting drug users (IDU)
      (ORa = 1.4; CI 95%, 1.2-1.6), and those patients with a prison record (ORa = 2.1;
      CI 95%, 1.9-2.4). CONCLUSIONS: In Spain, male AIDS patients, under age 40 years
      with a prison record and IDU have a higher risk of tuberculosis. Control measures
      for tuberculosis should therefore be intensified among these patients.

PMID- 9547732
TI  - [Trends in human immunodeficiency virus infection prevalence in
      homosexual/bisexual men in Madrid (1986-1995)].
AB  - BACKGROUND: We analysed the trend in seroprevalence for human immunodeficiency
      virus (HIV) in homosexual or bisexual men who voluntary requested the test in a
      sexually transmitted disease/HIV clinic in Madrid. PATIENTS AND METHODS: We
      studied 5,424 homo/bisexual non-injecting drug user (non-IDU) men, who came for
      the first time since 1986 to 1995. We analysed the HIV seroprevalence taken into
      account the year, age and exchange of sex by money. A hundred and thirty-six IDU
      homo/bisexual men were also attended during the same period and they were
      compared with non-IDU. RESULTS: HIV seroprevalence among the 5,424 non-IDU
      homo/bisexual men were 20.2%, rising from 19.6% in 1986 to 29.6% in 1990. After
      then, the trend decreased to 15.3% in 1995 (chi 2 for trend, 66.8; p < 0.0001).
      Average age was three years higher among seropositives (p < 0.0001), and showed
      an upward trend from 29.9 in 1986 to 34.6 in 1995 (p = 0.0059). Seroprevalence
      among homosexuals younger than 25 fell in the last years. One percent of
      individuals had ever practiced the prostitution. They were younger (average age,
      27.6), and their HIV seroprevalence were 25.9%. A hundred and thirty-six IDU
      homo/bisexual men were also attended for the first time, being 2.4% of overall
      homo/bisexual men. They had a higher seroprevalence (48.5%) than non-IDU (p <
      0.0001), and did not show any significative time-trend. CONCLUSIONS: A favourable
      evolution can be observed in HIV seroprevalence among homo/bisexual from Madrid,
      Spain, men who came to be tested, especially among the youngest. Prevention
      programs should make an effort to maintain this trend.

PMID- 9547734
TI  - [Master formulas for the treatment of obesity: an interminable history?].

PMID- 9547733
TI  - [Bacterial vaginosis: where are we?].

PMID- 9547735
TI  - [The 1st case in Spain of detection of occult squamous carcinoma using LIFE
      system].
AB  - LIFE system (lung imaging fluorescence endoscope) is a new system of detection
      for early lung cancer using a He-Cd laser through a conventional fiberoptic
      bronchoscope. This system is able to capture and processing the autofluorescence
      from the bronchial mucosa and to show it in a video screen in real time. In the
      screen the normal tissue appears in green colour and the neoplastic tissue in
      brown colour. The first studies performed with LIFE system show the same
      specificity of the conventional bronchoscopy but the sensibility is 50% higher.
      In this paper we present the first case of detection of a occult squamous cell
      carcinoma with sputum and bronchial aspiration cytology positive for carcinoma
      but chest X ray, CT scanner and bronchoscopy negative for lung cancer. The LIFE
      system was able to detect carcinoma in the carina.

PMID- 9547736
TI  - [Abdominal pain and weight loss in a 70-year-old man].

PMID- 9547737
TI  - [Calcium antagonists and their impact on coronary risk].

PMID- 9547738
TI  - [Publishing of clinical trials: methods and ethics].

PMID- 9547739
TI  - [Malignant neuroleptic syndrome associated to risperidone].

PMID- 9547740
TI  - [Pathophysiologic changes in patients with severe burns: role of hormones and
      chemical mediators].
AB  - The body's general response to serious thermal injury is characterized by
      increased vascular permeability immediately after injury and subsequent
      hypovolemic shock. Skeleto-muscular proteolysis, lipolysis, gluconeogenesis,
      increased metabolic rate, and a severe systemic inflammatory response induced by
      local infections or surgical procedures. The increased vascular permeability is
      mediated by histamine and numerous vasoactive substances, including serotonin,
      bradykinin, prostaglandins, leukotrienes, and platelet activating factor. Hyper
      metabolism is mediated by hormones such as catecholamines, glucagon, and
      particularly cortisol. In addition, among the putative mediators of the metabolic
      response to injury, attention has recently been focused on cytokines and lipid
      mediators which are mainly produced by activated reticuloendothelial cells.
      Cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor and
      cortisol responses are interrelated, since cytokines activate the hypothalamo
      adrenal axis. The cytokine storm seen in burn patients may be associated with
      depression of the immune system and with susceptibility to infection. Thermal
      injury can also lead to activation of the renin-angiotensin-aldosterone system,
      increased ADH production, and production of atrial natriuretic polypeptide to
      maintain the circulatory volume. Burn wound infections or surgical procedures can
      produce and perpetuate a mediator-induced systemic inflammatory response that may
      lead to multiple organ failure. Serum levels of interleukin-6 are very sensitive
      to surgical stress, and may be a useful indicator of the general condition of
      severely burned patients.

PMID- 9547741
TI  - [Early treatment for body fluid shifts and circulatory derangement in patients
      with extensive burns].
AB  - The initial postburn period is characterized by body fluid shifts and circulatory
      derangement, or so-called burn shock. The fluid shifts are mainly due to a marked
      increase in capillary permeability. This loss of capillary integrity is so great
      that colloid including albumin, readily disperse into the extravascular space.
      This is limited to the burned area when of 30% or less of the body surface area
      (BSA) is involved, but is found throughout the entire body when more than 30% of
      the BSA is involved. The tremendous fluid shifts from the intravascular to the
      extravascular space result in edema formation and hemoconcentration. Along with
      the reduction in intravascular volume, there is a rapid reduction in cardiac
      output which gradually returns to the normal level 24 to 48 hours after burn
      injury. Therefore fluid resuscitation should be initiated immediately after
      injury. Currently a number of methods for achieving adequate volume replacement
      are available. In this paper we review fluid resuscitation methods for patients
      with extensive burns and also introduce recent topics on new regimens for
      resuscitation.

PMID- 9547742
TI  - [Current treatment burn wounds: alternative wound coverage methods].
AB  - In patients with massive burn injuries and very limited skin donor sites, both
      acute-phase and long-term problems of skin loss must be solved by the use of
      alternative wound closure materials. Alternative materials can be used for either
      temporary wound coverage or for permanent wound closure. Recently, allogenic skin
      grafts have most commonly been used as alternative wound closure material.
      However, research is ongoing on many new materials to provide a readily available
      substitute for skin allografts for permanent wound closure. The best approach to
      the development of alternative permanent wound closure materials is to
      incorporate the host's own cellular and structural components. Four general
      strategies have been devised so far based on the type of matrix structure and
      cellular content: allografts; cultured epidermal grafts; dermal matrix grafts;
      and cultured-dermal matrix composite grafts. Several approaches using combined
      alternative wound closure materials have been used, including transplantation of
      artificial dermal matrix with thin epidermal autografts, and transplantation of
      artificial dermal matrix containing human fibroblasts. Ultimately, the best
      candidate materials for permanent wound closure after extensive burn injury must
      be determined in prospective, randomized, controlled clinical trials.

PMID- 9547743
TI  - [Metabolism and nutritional support after burn injury].
AB  - The nutritional status of the burn patient plays a major role in the ability to
      ward off an infectious challenge. The immune and inflammatory systems can be
      modulated by nutritional support, and therefore this article focuses on the
      nutritional support after burn injury. The hypermetabolic response that occurs
      after burn injury is characterized by a greater magnitude than that observed
      after any other form of trauma. The hypothesis that gut-or wound-derived
      bacterial translocation is one of the major triggers of the hypermetabolic
      response has attracted attention recently. The first set of goals of nutritional
      support is to prevent starvation and nutrient deficiencies, and the second is to
      provide the correct amount of nutrients prevent injury-related adverse
      physiologic complications. The route and timing of nutritional support are most
      important. Enteral alimentation appears to preserve the host immune function and
      to attenuate the hypermetabolic response by preserving the intestinal mucosal
      barrier. Immediate enteral feeding is superior to delayed enteral feeding, even
      though only limited amounts of enterally administered nutrients are absorbed
      during the early days postburn.

PMID- 9547744
TI  - [Immunological alterations after extensive burn injury].
AB  - It is recognized that extensively burned patients have an increased
      susceptibility to infection and often succumb to multiple organ failure related
      to sepsis. Numerous investigations performed over more than 30 years have
      demonstrated immunologic abnormalities in burn patients, including changes in
      serum immunoglobulin and opsonin levels, alterations in the complement system,
      impairment of phagocyte and neutrophil function, suppression of delayed
      hypersensitive reactions, and prolongation of allograft survival. Recent progress
      in immunology has shown that inadequate production of both cytokines and
      arachidonic acid derivatives is profoundly involved in immunosuppression after
      severe burn injury. A better understanding of immunologic status is necessary to
      reduce the mortality rate from infection in extensively burned patients. This may
      also lead to discovering the therapeutic control mechanisms for their immunity.

PMID- 9547745
TI  - [Sepsis in extensive burned patients].
AB  - The prognosis of extensively burned patients is dependent upon the presence of
      sepsis. The more extensive the burns, the more likely patients are to become
      septic. Although recently the frequency of burn wound sepsis has been decreased
      due to the early excision of necrotic tissue, that of sepsis resulting from
      respiratory tract infection has increased. Staphylococcus aureus (methicillin
      resistant S. aureus) and Pseudomonas aeruginosav are the agents most likely to
      cause infections. Sepsis syndrome also results from bacterial translocation (BT),
      in which gut bacteria and/or endotoxins are thought to enter the portal
      bloodstream and/or lymphosystem. The pathophysiological mechanism of sepsis is
      the increased release of inflammatory mediators and resulting imbalances between
      these substances and their antagonists. In cases of severe sepsis, the sequelae
      of the imbalance between inflammatory mediators and their antagonists can lead to
      endothelial injury, DIC, and finally MODS. Strategies against the occurrence of
      sepsis include hospital-wide infection control measures, blockage of infection
      routes, and administration of antibiotics. The early initiation of nutritional
      management, preferably by the enteral route, to enhance immune system function
      and minimize the occurrence of BT is recommended. Several drugs to control
      inflammatory mediator release are currently under development and are expected to
      be used clinically in future.

PMID- 9547746
TI  - [Immediate burn wound excision and grafting decreases the mortality rate and
      hospital stay duration in extensive burn patients].
AB  - The treatment of patients with extensive burn injuries has begun to changed in
      recent years. Traditional methods have consisted of dressing the burn wound with
      topical antimicrobials, tubbing the patient daily, encouraging the shoughing off
      of eschar using surgical debridement as necessary, and finally, closing the
      granulating wound with split-thickness skin grafts after 2 to 4 weeks. An
      alternative and more radical procedure is now being used with increasing
      frequency: complete surgical excision of the eschar is performed as soon as the
      patient is hemodynamically stable after resuscitation from burn shock. From 1991
      to 1997, we performed immediate burn wound excision and grafting in 15 extensive
      burn patients within 24 hours after injuries. The mean burn surface area (BSA)
      was 48 +/- 20%, and the mean burn index was 44 +/- 19. The mean prognostic burn
      index (PBI = burn index + age) was 94 +/- 23. There were 5 deaths, for an overall
      mortality rare of 33%, which is less than that experienced by 11 other burn units
      in Tokyo (51.4%). The duration of hospital stay of survivors was approximately 1
      day/%BSA.

PMID- 9547747
TI  - [Clinical and pathophysiologic problems associated with smoke inhalation injury].
AB  - Smoke inhalation injury is one of the primary determinants of survival following
      major burn injury. The primary site of injury in smoke inhalation appears to be
      the small airway rather than the alveoli, and thus small airway occlusion caused
      by edema and pseudomembrane formation are the primary mechanisms of progressive
      hypoxia. Ventilation-perfusion (VA/Q) alterations after smoke inhalation are
      characterized by increased blood flow to low VA/Q compartments, although an
      increase in true shunt (VA/Q = 0) was not a consistent finding. This differs
      considerably from most adult respiratory distress syndrome (ARDS) patients or
      oleic acid-induced lung edema models, in which an increase in true shunt is the
      major mechanism of hypoxia. Such differences lead to different responses to
      nitric oxide (NO) inhalation therapy, and NO does not improve oxygenation and
      outcome in patients with smoke inhalation injury. In the treatment of inhalation
      injury, meticulous removal of pseudomembrane by fiberoptic bronchoscopy is
      essential, the use of high concentrations of oxygen should be avoided since it
      can cause absorption atelectasis. High-frequency percussive ventilation is a
      suitable treatment for inhalation injury, as it improves oxygenation and
      facilitates removal of pseudomembrane.

PMID- 9547748
TI  - [Electrical injury].
AB  - Electrical injury can be classified into true electrical injury, are burn. In
      true electrical injury, large or small, dry, dark brown necrotic wounds (electric
      current spots) are observed on the skin at the entrance and exit sites of the
      electric current, and progressive necrosis develops in surrounding tissues. As
      generalized symptoms, ventricular fibrillation, respiratory arrest, and loss of
      consciousness may be observed temporarily immediately after the injury. Necrosis
      also occurs in deep tissues including muscles, and pathology resembling crush
      injury is seen. Myoglobin released into the circulation due to muscle necrosis
      tissue causes myoglobinuria and increases the risk of acute renal failure.
      Treatment consists of emergency resuscitation and fluid supplementation with
      lactated Ringer's solution. However, more fluid should be administered than in
      cases of common burns to accelerate urinary excretion of myoglobin in the
      circulation. For local treatment, debridement should be performed in areas with
      clear third-degree burns, but in the presence of progressive necrosis, repair and
      reconstruction after debridement should be postponed for 2-3 weeks.

PMID- 9547749
TI  - Measurement of temporal asymmetries of glucose consumption using linear profiles:
      reproducibility and comparison with visual analysis.
AB  - AIM: One approach to regionally analyze temporal glucose consumption consists in
      drawing linear profiles over the maximal values measured in the temporal cortical
      ribbon. The aim of our study was to test the reproducibility of this method and
      to compare its diagnostic performance to that of visual analysis in patients with
      complex partial seizures (CPS). METHODS: Regional cerebral glucose consumption
      (rCMRGIc) was measured interictally in 25 CPS patients and 10 controls using F-18
      deoxyglucose and the positron emission tomography (PET) camera ECAT EXACT 47. The
      PET scans were visually analyzed for the occurrence of unilateral temporal
      hypometabolism. Furthermore, rCMRGIc was quantified on six contiguous coronal
      planes by manually tracing maximal values of temporal glucose consumption, thus
      creating line profiles of temporal glucose consumption for each side. Indices of
      asymmetry (ASY) were then calculated from these line profiles in four temporal
      regions and compared to the corresponding 95% confidence intervals of the control
      data. All analyses were performed by two observers independently from each other
      and without knowledge of the clinical findings. RESULTS: The agreement between
      the two observers with regard to focus lateralization was 96% (kappa = 0.93) on
      visual analysis and 100% (kappa = 1) on quantitative analysis. There was an
      excellent agreement with regard to focus lateralization between visual and
      quantitative evaluation (kappa = 0.8). CONCLUSION: Quantitation of local temporal
      rCMRGIc by using linear profile analysis is highly reproducible; for the
      lateralization of epileptogenic foci, however, this method does not possess
      significant advantages over the visual evaluation of the scans.

PMID- 9547750
TI  - Quantitative estimation of I-123-Iomazenil receptor binding in temporal lobe
      epilepsies using two SPECT acquisitions--comparison with the regional cerebral
      blood flow and a compartment model.
AB  - AIM: To compare published fractional rate constants of I-123-Iomazenil (IMZ) and
      C-11-Flumazenil (three-compartment/four-parameter model) with a I-123-Iomazenil
      receptor index calculated from two SPECT acquisitions and to compare the receptor
      index of the epileptogenic area with the contralateral side in patients with
      unilateral temporal lobe epilepsies. METHODS: 28 patients were studied. 13/28
      patients had a drug-resistant unilateral temporal lobe epilepsy with a successful
      focus localisation performed by an extensive video/EEG monitoring. 15 other
      patients with clinically suspected focal epilepsy and a normal MRI and IMZ SPECT
      scanning were used as controls. SPECT scanning was performed in all patients 15
      and 100 min after intravenous injection of 111 MBq IMZ and 10 min after
      application of 740 MBq Tc-99m-HMPAO. Quantification of the regional uptake was
      performed using ROI-technique and the specific and non-specific binding of IMZ
      was calculated. The receptor index was calculated by the difference of the
      specific binding from 15 to 100 min p.i. divided by the time interval. RESULTS:
      The receptor index showed a linear correlation with recently published fractional
      rate constants k3 (r = 0.69 and 0.67; p = 0.15) and a moderate correlation with
      the k4 constant (-0.53 and -0.43; p = 0.28) by the means of C-11-Flumazenil PET
      and I-123-Iomazenil SPECT studies, respectively. However, statistical
      significance was not reached due to the few data points available from the
      published reports. Furthermore, the IMZ receptor index was lower in the
      epileptogenic area of patients with unilateral temporal lobe epilepsies compared
      with their contralateral side (p = 0.02; Wilcoxon-test). The IMZ receptor index
      showed a weak correlation with the regional cerebral blood flow independent of
      the evaluated region (r < 0.4; p < 0.05). CONCLUSION: The IMZ receptor index
      indicated to be a simple routine approach to estimate the fractional rate
      constant k3 (r = 0.67). The lower value of the receptor index within the
      epileptogenic area might be due to a lower receptor density. However in further
      studies, IMZ might be a helpful tool to find out subtle changes of the receptor
      affinity due to its approximately 30-fold higher ligand-receptor affinity
      compared to C-11-Flumazenil.

PMID- 9547751
TI  - [Esophageal scintigraphy of Zenker's diverticula before and after
      diverticulotomy].
AB  - AIM: The filling and evacuation of Zenker's diverticula were scintigraphically
      examined before and after operation to quantify their functional relevance. These
      results were correlated with the symptoms of the patients and the findings of the
      barium swallow x-ray examination using cineradiography. METHODS: Sequential and
      static esophageal scintigraphies were performed in 17 patients with Zenker's
      diverticulum before and after laser surgical diverticulotomy. We used a gamma
      camera system in 45 degrees LAO-position after application of 15 ml of tea which
      was marked with 99mTc-DTPA. Filling and evacuation of the diverticulum were
      expressed in proportion to the administered activity. Relative volumes of the
      diverticula were obtained from cineradiography by using the height of the
      neighbouring cervical vertebra, and the clinical symptoms were divided into 4
      groups. RESULTS: Zenker's diverticula could be verified visually and
      quantitatively by scintigraphy. The precise temporal course of the reduction of
      activity in the diverticulum was exactly determined. The scintigraphic retentions
      correlated with the x-ray volumes with a coefficient ranging from 0.55 to 0.85.
      Clinical symptoms also were not very closely related to scintigraphic and x-ray
      findings, respectively. CONCLUSION: The esophageal scintigraphy allows
      quantification of the filling and evacuation of Zenker's diverticula, thus it is
      suitable for objectivization of the functional relevance of the diverticula.
      That's why the esophageal scintigraphy should be taken to the diagnosis of
      diverticula in addition to the clinic and the x-ray examinations. The method is
      especially useful to evaluate the results after diverticulotomy.

PMID- 9547752
TI  - [Optimization of PET image quality by means of 3D data acquisition and iterative
      image reconstruction].
AB  - PURPOSE: In the recent past, several algorithms have been developed in order to
      transform 3D sinograms acquired at volume PET systems into 2D data sets. These
      methods offer the possibility to combine the high sensitivity of the 3D
      measurement with the advantages of iterative 2D image reconstruction. The purpose
      of our study was the assessment of this approach by using phantom measurements
      and patient examinations. METHODS: The experiments were performed at the latest
      generation whole-body PET system ECAT EXACT HR+. For 2D data acquisition, a
      collimator of thin tungsten septa was positioned in the field-of-view. Prior to
      image reconstruction, the measured 3D data were sorted into 2D sinograms by suing
      the Fourier rebinning (FORE) algorithm developed by M. Defrise. The standard
      filtered backprojection (FBP) method and an optimized ML/EM algorithm with
      overrelaxation for accelerated convergence were employed for image
      reconstruction. The spatial resolution of both methods as well as the convergence
      and noise properties of the ML/EM algorithm were studied in phantom measurements.
      Furthermore, patient data were acquired in the 2D mode as well as in the 3D mode
      and reconstructed with both techniques. RESULTS: At the same spatial resolution,
      the ML/EM-reconstructed images showed fewer and less prominent artefacts than the
      FBP-reconstructed images. The resulting improved detail conspicuously was
      achieved for the data acquired in the 2D mode as well as in the 3D mode. The best
      image quality was obtained by iterative 2D reconstruction of 3D data sets which
      were previously rebinned into 2D sinograms with help of the FORE algorithm. The
      phantom measurements revealed that 50 iteration steps with the optimized ML/EM
      algorithm were sufficient to keep the relative quantitation error below 5%.
      CONCLUSION: Our measurements show that the image quality in 3D PET can be
      improved by using iterative reconstruction techniques. The concept of 3D data
      acquisition and combining the FORE algorithm with 2D ML/EM reconstruction can
      readily be employed in clinical practice since the computation time is not
      considerably longer than that in iterative reconstruction of true 2D data.

PMID- 9547753
TI  - [Dosimetry fundamentals of endovascular therapy using Re-188 for the prevention
      of restenosis after angioplasty].
AB  - AIM: Various radionuclides can be used for endovascular brachytherapy. A new
      concept is to inflate the balloon of a dilatation catheter with a radioactive
      solution. Re-188 can be eluted from a generator system and is available daily.
      The aim of this study was to obtain dosimetric data for this radionuclide.
      METHODS: The dose decrease of Re-188 was calculated and measured with a TLD
      system radial to a balloon catheter typically used in cardiology (diameter: 3 mm,
      length: 20 mm). RESULTS: Using a specific activity of 370 MBq/ml a dose of 0.3 Gy
      could be achieved within 1 min in a TLD in contact with the balloon. Paired TLDs
      differed about 3%. A fast dose reduction of 50% and 10% were stated within 0.5 mm
      and 2.5 mm, respectively. Calculated and measured values were in good agreement.
      The data are comparable to those known for Y-90. CONCLUSION: Calculations of dose
      distribution are consistent with TLD measurements of Re-188. Using a specific
      activity of 1.85 GBq/ml, a dose of 10-15 Gy at the coronary artery wall can be
      achieved within 2-3 min. Compared to radioactive stents or wires the use of this
      liquid beta-emitter is a simple alternative for prevention of the restenosis
      following the angioplasty.

PMID- 9547754
TI  - Positive I-123-MIBG-scintigraphy in osteosarcoma.
AB  - I-123-MIBG scintigraphy has become a standard imaging technique in the detection
      of neuroendocrine or neurocrest derived tumors, especially neuroblastoma and
      pheochromocytoma. We report on a positive I-123-MIBG uptake in a pediatric
      osteosarcoma patient and demonstrate, that unusual results still occur with this
      established imaging method.

PMID- 9547755
TI  - [18F]fluoride PET indicates reduced bone formation in severe glucocorticoid
      induced osteoporosis.
AB  - A 61-year-old female patient presenting with mixed connective tissue disease
      (Sharp syndrome), underwent a long-term high dose glucocorticoid treatment
      because of multiple organ manifestations. Under steroid therapy she developed
      severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET
      study in this patient revealed reduced fluoride influx in non-fractured
      vertebrae. This finding corresponds to pathogenetic concepts which propose an
      inhibition of bone formation as major cause of glucocorticoid-induced
      osteoporosis. In the light of the presented case it seems to be promising to
      evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis.

PMID- 9547756
TI  - [Occult fracture of the femoral neck fractures of the proximal femur].
AB  - Bone scintigraphy is a highly sensitive method for the detection of fractures. In
      case a trauma and clear clinical signs are evident, but the radiography is
      inconspicuous, bone scintigraphy may lead to the final diagnosis. In the present
      case of an occult fracture in the proximal femur only scintigraphy indicated the
      fracture, which then was proved topographically by magnetic resonance imaging.

PMID- 9547757
TI  - Biology of addiction.
AB  - It is unknown why an individual becomes addicted to drugs. Substance abuse is
      typified by a wide variety of use patterns and variation in individual responses.
      Behavioral psychology teaches that if something either increases the individual's
      sense of pleasure or decreases his or her discomfort, then the individual is
      likely to repeat the behavior. Evidence has suggested that abusers report a sense
      of pleasure when they use substances because of the ability of the substance to
      stimulate the release of neurotransmitters known to be used by the brain's
      pleasure system. This article provides an overview of the substance-related
      disorders, including their definition in the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV).

PMID- 9547758
TI  - Pharmacology of drug transfer across the placenta.
AB  - The effect of drugs in the fetus can be thought of in terms of the dose-response
      based on a knowledge of the general principles by which drug is transferred from
      the mother to the fetus. Fetal drug concentration, which determines the fetal
      response, is a function of the maternal concentration, the placental
      permeability, the fetal drug clearance, and differences in protein binding and
      ionization between the maternal and fetal plasma.

PMID- 9547759
TI  - Detection of drug use during pregnancy.
AB  - Several methods of drug testing are efficacious in identifying and monitoring
      drug use during pregnancy. Urine screening remains the most commonly used method
      despite the limited period during which drugs can be detected. Hair has been
      recognized as a possible alternate test specimen, but wider acceptance of hair
      testing must await better understanding of drug disposition in hair, answers to
      the issues relating to interpretation, and the development of less demanding
      laboratory techniques. Regardless of the matrix used, proper interpretation of
      the results of drug testing requires familiarity with the sensitivity,
      specificity, and limitations of the laboratory methodologies employed. Moreover,
      unconfirmed positive results may actually be false-positives and must be
      interpreted with caution, particularly if they are the basis for major clinical
      decisions.

PMID- 9547760
TI  - Marihuana and tobacco use in pregnancy.
AB  - Marihuana and tobacco smoking are two of the most commonly abused substances in
      pregnancy. Smoke from both agents contain a multitude of potentially active
      components, which make them difficult to study. Both have been associated with
      adverse effects in pregnancy in animal and human studies. Data on marihuana use
      during pregnancy have been conflicting. There is much evidence, however,
      demonstrating adverse pregnancy outcomes associated with cigarette smoking which,
      fortunately, can be reversed with smoking cessation.

PMID- 9547761
TI  - Fetal alcohol syndrome. Hearing, speech, language, and vestibular disorders.
AB  - Fetal alcohol syndrome (FAS) refers to a pattern of anomalies that include
      craniofacial, CNS, growth, and various sensory anomalies. We have observed that
      FAS is associated with four kinds of hearing disorders: (1) developmentally
      delayed auditory function, (2) sensorineural hearing loss, (3) intermittent
      conductive hearing loss owing to recurrent serous otitis media, and (4) central
      hearing loss. As is the case with other syndromes associated with craniofacial
      anomalies and hearing impairments, speech and language pathologies also are
      common in FAS patients. Although auditory and vestibular systems arise from
      similar embryological tissue, vestibular dysfunction is variable in FAS. Early
      identification and intervention to treat hearing, language, and speech problems
      should improve the functional level of FAS in children.

PMID- 9547762
TI  - Cocaine in pregnancy. Recent data on maternal and fetal risks.
AB  - Cocaine continues to be abused during pregnancy, creating increased demands on
      the health care system. Epidemiology and basic science research have identified
      and confirmed risks of adverse maternal and fetal effects when cocaine is used
      during pregnancy. These effects of cocaine in pregnant women often are influenced
      by a number of confounding variables. This article reviews those cocaine effects
      as well as recent data, which examine in greater detail the risks of adverse
      outcomes of prenatal cocaine exposure during pregnancy.

PMID- 9547763
TI  - Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.
AB  - Based on findings in humans and the confirmation of prenatal exposures in
      animals, amphetamines and methamphetamines increase the risk of an adverse
      outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal
      growth reduction deficits that have been seen in infants exposed to amphetamines
      during pregnancy have all been reproduced in animal studies involving prenatal
      exposures to amphetamines. The differential effects of amphetamines between
      genetic strains of mice and between species demonstrate that pharmacokinetics and
      the genetic disposition of the mother and developing embryo can have an enormous
      influence on enhancing or reducing these potential risks. The effects of prenatal
      exposure to amphetamines in producing altered behavior in humans appear less
      compelling when one considers other confounding variables of human environment,
      genetics, and polydrug abuse. In view of the animal data concerning altered
      behavior and learning tasks in comparison with learning deficits observed in
      humans, the influence of the confounding variables in humans may serve to
      increase the sensitivity of the developing embryo/fetus to prenatal exposure to
      amphetamines. These factors and others may predispose the developing conceptus to
      the damaging effects of amphetamines by actually lowering the threshold of
      susceptibility at the sites where damage occurs. Knowledge of the effects of
      prenatal exposure of the fetus and the mother to designer amphetamines is
      lacking. Based on the few studies in which designer drugs have been examined in
      animal models, more questions are raised than answered. Possible reasons why no
      malformations or significant fetal effects were found in the study by St. Omer
      include the genetic strain of rat used, the conservative exposure profile, or the
      fact that the placenta metabolized MDMA before reaching the embryo. These
      questions underscore the need for further investigations concerning the prenatal
      exposure effects of designer compounds and the effects of amphetamine and
      methamphetamine in general.

PMID- 9547764
TI  - Opioid dependence during pregnancy. Effects and management.
AB  - This article describes the complex problems associated with opioid dependence
      during pregnancy. Medical, obstetric, and psychosocial problems are presented.
      Methadone maintenance for the treatment of opioid dependence is described in this
      article. Specific issues of appropriate methadone dose during pregnancy, medical
      withdrawal, and the relationship of methadone dose and the severity of neonatal
      abstinence also are discussed.

PMID- 9547765
TI  - Inhalant abuse in pregnancy.
AB  - Information from a variety of sources suggests the possibility of adverse effects
      of maternal inhalant abuse, although a well-controlled, prospective study in this
      area has not been conducted. One source of this concern is the data from
      occupational exposure to some of the abused solvents, specifically toluene and
      TCE, with numerous reports suggesting increased spontaneous abortion and fetal
      malformations. There are also data suggesting decreased fertility and an
      increased risk for spontaneous abortion in health care workers exposed to nitrous
      oxide. The relevance of these studies to problems of inhalant abuse is not clear.
      Although the chemicals involved are the same, there are many differences in the
      exposure parameters, the populations exposed, and the types of associated risk
      factors. Nonetheless, there are more than 100 cases reported in the literature of
      children born to solvent-abusing mothers. Many of these children were small at
      birth, and some have craniofacial abnormalities not unlike that seen in children
      with FAS. In the few studies reporting the findings of follow-up in these
      children, some evidence has been obtained for retardation in growth and
      development and for residual deficits in cognitive, speech, and motor skills.
      Clearly, more research is needed to rule out the concomitant risk factors and to
      identify specific chemicals and patterns of use associated with adverse effects.
      Animal studies provide more direct evidence that prenatal exposure to toluene or
      TCE can produce reduced birth weights, occasional skeletal abnormalities, and
      delayed neurobehavioral development, even under conditions designed to mimic
      inhalant abuse patterns. Additional research is needed to identify other
      chemicals with adverse effects, critical periods of exposure, effects of
      combinations of inhalants, or interactions with drugs of abuse. The research
      literature seems sufficient to alert clinicians to possible problems in patients
      who abuse inhalants while pregnant. Diagnosis and good prenatal care for these
      women are important. The evidence for neonatal withdrawal is limited at this
      time; however, infants born to women who have recently used inhalants should be
      observed carefully for an alcohol-like withdrawal syndrome. Although it is not
      possible to link a specific birth defect or developmental problem in the child of
      an inhalant abuser to prenatal exposure to a specific chemical, it is clear that
      inhalant abuse and its associated lifestyle place children at increased risk. A
      wider appreciation of this is needed among health care professionals and the
      general public.

PMID- 9547766
TI  - The impact of prenatal drug exposure on the neonate.
AB  - Several social or recreational drugs singly or together have demonstrated effects
      on the fetus and neonate, with those effects extending into adulthood. The use of
      recreational drugs during pregnancy remains a major health problem, with adverse
      effects including higher rates of fetal distress and demise, lower Apgar scores,
      growth retardation, and adverse neurodevelopmental outcome. Ethanol has the most
      profound effects, with physical stigmata of the drug seen in one third of exposed
      infants. In children without the affected physical appearance, profound
      neurodevelopmental sequelae have been demonstrated. Other drugs, such as cocaine,
      heroin, amphetamines, and nicotine, have been associated with impaired fetal
      growth and acute withdrawal during the neonatal period. Subsequently, these
      infants and children have an increased risk for altered neurodevelopment and long
      term health status. Long-term follow-up and assessment are essential. The risk of
      neonatal withdrawal or abstinence syndrome is greatest with narcotic drugs but
      has been found to occur in neonates following exposure to cocaine, nicotine, and
      amphetamines. Early treatment with tincture of opium, paregoric, or phenobarbital
      is crucial. Assessment of the overall health status of the infant should include
      growth parameters, signs and symptoms of infection (especially hepatitis,
      syphilis, and immunodeficiency viruses), and neurobehavioral function. Such
      assessments should not be limited to the newborn period, as neurodevelopmental
      sequelae may not be manifest until later in infancy and childhood. In addition,
      evaluation of the social milieu is warranted because of the increased risk for
      neglect and abuse of drug-exposed infants and children. Early intervention,
      maternal drug rehabilitation treatment, and parenting classes are frequently
      prescribed, but their efficacy is variable. Further investigations should study
      the potential benefits of these recommendations.

PMID- 9547767
TI  - Breast-feeding and drug exposure.
AB  - Breast-feeding provides important benefits to mother and infant and should be
      strongly encouraged as the optimal feeding choice for most infants. In the mother
      with an ongoing illicit drug abuse problem, the risks posed to the infant are
      substantial and outweigh the benefits of breast-feeding in most cases. Moderate
      use of alcohol, cigarettes, or caffeine is compatible with breast-feeding.

PMID- 9547768
TI  - An introduction to reactive oxygen species and their possible roles in substance
      abuse.
AB  - There is a growing body of information relating diverse diseases and the
      consequences of injury to generation and toxicity of reactive oxygen species
      (ROS). Recently, it has been shown that the fetus and its membranes are also
      vulnerable to this toxicity, suggesting that a number of obstetric diseases may
      result from exposure to ROS, which are ubiquitous in aerobic organisms.
      Endogenous antioxidants, including superoxide dismutase, catalase, and
      glutathione peroxidase are essential for defense against ROS. It is significant
      that all antioxidants appear to be down-regulated in the fetus and membranes,
      suggesting the possibility that any process that further depresses their
      activities or increases the burden of ROS may compromise fetal development or
      maternal health. When permitted to accumulate, ROS can damage all classes of
      macromolecules, including lipids, proteins, and nucleic acids. Toxicity includes
      mutation, protein degradation, and lipid peroxidation, which can severely disturb
      membrane permeability and alter intracellular calcium and pH. An understanding of
      the generation and toxicity of ROS should help to define their potential roles in
      obstetric disease and lead to innovative preventive and therapeutic approaches.

PMID- 9547769
TI  - Moral and social issues regarding pregnant women who use and abuse drugs.
AB  - Pregnant women who abuse drugs, such as alcohol, cocaine, and marihuana may face
      a variety of legal and social responses, including involuntary commitment, forced
      treatment, and criminal sanctions. These programs are intended to remedy apparent
      maternal-fetal conflicts but paradoxically may encourage some women to avoid
      beneficial medical and social services or to seek abortion. Although pregnant
      women have ethical duties to give due consideration to their offspring, these
      moral obligations fail to justify coercive and punitive programs regarding
      substance abuse. Coercive fetal protection policies may undermine pregnant
      women's trust and cooperation, violate their autonomy, weaken our civil
      liberties, and raise a host of ethical problems relating to race, gender, and
      class prejudice. Education and drug treatment programs, rather than punitive and
      coercive measures, may better help pregnant women fulfill their moral duties to
      refrain from abusing substances.

PMID- 9547770
TI  - The drug court. A new strategy for drug use prevention.
AB  - The concept of Drug Treatment Court is relatively new and is an innovative
      response by local communities to deal with the escalation of criminal activity
      associated with substance abuse. The frequency of repeated offenses by drug
      users, the overcrowding of jail space, and a diminished sense of community well
      being contributed to the motivation to look for a new approach by the criminal
      justice system--the creation of Drug Treatment Courts. This article reviews the
      strategy behind this creation.

PMID- 9547771
TI  - Erbium:YAG laser-assisted cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: To assess the safety and efficacy of erbium:YAG laser
      assisted cataract removal. PATIENTS AND METHODS: A total of 15 patients underwent
      cataractous lens removal. All the patients had a visual acuity of 20/50 or worse
      secondary to senile cataract. The endothelial cell count was calculated
      preoperatively and at 6 weeks postoperatively. A 2.94-micron-wavelength erbium:
      YAG laser with a zirconium-fluoride fiber optic and silica tip was used to
      fracture and emulsify the nucleus. The erbium:YAG laser was chosen due to its
      high absorption in water, a primary component of a cataractous lens. RESULTS: The
      postoperative visual acuity was 20/30 or better in all the eyes that were treated
      with surgery. The endothelial cell loss at 3 months was 0% to 10%. No laser
      related complications were noted. A conversion to an ultrasound surgical
      technique was utilized in six cases. Vitreous loss occurred in one case due to
      the posterior extension of an anterior capsulotomy tear. CONCLUSION: This study
      demonstrated the ability of an erbium:YAG laser system to safely and effectively
      emulsify the lens nucleus. Laser-assisted cataract surgery is a promising new
      clinical procedure.

PMID- 9547772
TI  - Outcomes of vitreoretinal surgery in patients with X-linked retinoschisis.
AB  - BACKGROUND AND OBJECTIVE: To assess the outcomes of vitreoretinal surgery in the
      treatment of vision-threatening posterior segment complications of X-linked
      retinoschisis. PATIENTS AND METHODS: The authors performed a retrospective
      analysis of 16 eyes from 11 patients who underwent vitreoretinal surgery. All the
      patients had a documented positive family history of X-linked retinoschisis, and
      all patients had bilateral macular disease. RESULTS: The ages of the patients
      ranged from 14 months to 37 years (mean age 15.1 years; median age 11.5 years),
      and postoperative follow-up ranged from 3 months to 10 years (mean 2.8 years;
      median 1 year). The indications for surgical intervention included rhegmatogenous
      retinal detachment (12 eyes), vitreous hemorrhage (2 eyes), progression of the
      schisis cavity through the fovea (2 eyes), cataract associated with a persistent
      hyperplastic primary vitreous-like condition (2 eyes), and exudative maculopathy
      (1 eye). The primary surgical intervention included pars plana vitrectomy alone
      (7 eyes), pars plana vitrectomy and pars plana lensectomy (4 eyes), and a scleral
      buckle procedure alone (5 eyes). Surgical success (defined as reattachment of the
      retina, removal of media opacities, or arrest of schisis progression) was
      achieved in 14 of 16 eyes, after an average of 1.2 procedures per eye. The major
      reason for reoperations was recurrent retinal detachment due to proliferative
      vitreoretinopathy. Two eyes were eventually enucleated due to pain associated
      with neovascular glaucoma resulting from recurrent retinal detachment. Of the
      remaining 14 eyes, visual acuity improved in 8 eyes and remained unchanged in 6
      eyes. CONCLUSION: Vitreoretinal surgery is often helpful in stabilizing or
      improving visual function in patients with posterior segment complications from X
      linked retinoschisis.

PMID- 9547773
TI  - The progressive outer retinal necrosis syndrome: successful treatment with
      combination antiviral therapy.
AB  - BACKGROUND AND OBJECTIVE: To assess a two-drug combination of antiviral therapy
      for the progressive outer retinal necrosis syndrome (PORN), given the current
      poor outcome with acyclovir alone. PATIENTS AND METHODS: A retrospective review
      was performed on six consecutive patients who were diagnosed with PORN and were
      treated with various combinations of intravenous or oral plus intravenous
      antiviral therapy. The relative efficacies of these modalities were compared.
      RESULTS: Six eyes of six patients showed active retinitis at the time of
      presentation. Three patients had unilateral retinitis, and the remaining patients
      had necrotic, end-stage disease in their fellow eye. All the patients were
      treated with combination therapy, consisting of either ganciclovir and acyclovir
      (three patients), foscarnet and ganciclovir (two patients), or foscarnet and
      acyclovir (one patient). Standard induction doses were employed. During the
      combination therapy, all six eyes showed resolution of the retinitis, manifested
      by complete fading of the original retinal lesions and an absence of new lesion
      formation. At the final follow-up, the areas of prior active retinitis had
      resolved and remained quiescent. A mild recurrence developed in one eye when
      ganciclovir and foscarnet were both tapered to a single daily dose. This
      recurrence promptly resolved with reinduction (twice daily) dosing. Two patients
      maintained a visual acuity of 20/50 or better in their involved eye for the
      duration of follow-up (38 and 27 weeks, respectively). One patient maintained a
      visual acuity of 20/40 for 14 weeks. The remaining three patients had macula-off
      retinal detachments despite resolution of active retinitis. In addition, for the
      duration of follow-up, one of the three patients with unilateral disease had
      retinitis in the uninvolved eye; all three uninvolved fellow eyes maintained a
      visual acuity of 20/20. One patient had progressive optic atrophy. CONCLUSIONS:
      Prolonged combination antiviral therapy for PORN may successfully arrest the
      progression of retinitis, maintain remission, and prevent involvement of the
      fellow eye. Furthermore, if aggressive therapy is begun early, good vision may be
      preserved.

PMID- 9547774
TI  - Oculocardiac reflex during retinal surgery using peribulbar block and nitrous
      narcotic anesthesia.
AB  - BACKGROUND AND OBJECTIVES: This study was designed to examine the effects of
      local and general anesthesia on the oculocardiac reflex (OCR) in adults during
      retinal detachment surgery, with an aim of determining the safest type of
      anesthesia and on which extraocular muscle traction causes a higher incidence of
      OCR. PATIENTS AND METHODS: The study was performed on 30 American Society of
      Anesthesiologists-I patients (age range 40-60 years) who were undergoing retinal
      detachment surgery. Fifteen patients underwent surgery with general anesthesia
      and 15 were given a local peribulbar block. A fixed traction of 400 g was applied
      to all the extraocular muscles, and the heart rate, rhythm, and electrocardiogram
      of each patient was monitored. RESULTS: The overall incidence of OCR was higher
      with general anesthesia (63.3%) than with local anesthesia (14.4%). There was a
      significant decrease in heart rate for the rectus muscles (P < .0005) as well as
      the oblique muscles (P < .005) during traction with general anesthesia. All four
      rectus muscles were equally sensitive in eliciting the reflex. The incidence of
      dysrhythmias was 20% with general anesthesia and 6.67% with local anesthesia.
      CONCLUSION: This study showed that local anesthesia produces less bradycardia and
      ectopic arrhythmias and, therefore, may be safer and better than general
      anesthesia for surgeries in which traction of extraocular muscles is required.

PMID- 9547775
TI  - The accuracy of finger tension for estimating intraocular pressure after
      penetrating keratoplasty.
AB  - BACKGROUND AND OBJECTIVE: Intraocular pressure (IOP) estimation by Goldmann
      tonometry is inaccurate in the immediate postoperative period after penetrating
      keratoplasty. For this reason, many corneal surgeons use a finger tension (FT)
      IOP estimation technique in the early post-keratoplasty period. The authors
      performed a prospective clinical study to evaluate the accuracy of this
      traditional technique. PATIENTS AND METHODS: FT estimates were performed by three
      experienced corneal surgeons on 68 patients on the first and second days after
      penetrating keratoplasty. These estimates were compared with MacKay-Marg (MM)
      tonometry readings for these patients. RESULTS: The mean confident FT from the
      pooled data of the three surgeons exceeded the MM reading by 5.0 mm Hg (22.6 vs.
      17.6). The mean FT exceeded the MM reading by only 3.9 mm Hg for the most
      accurate surgeon. Some observers were significantly more accurate than others,
      however, lid edema and tenderness of the globe markedly diminished the FT
      accuracy of all of the observers at significance levels of P < .001 and P < .01,
      respectively. Among all of the FT estimates, in only one patient (2%) did the FT
      underestimate the MM reading by more than 10 mm Hg. CONCLUSION: The authors'
      results suggest that for some patients, and for some surgeons, the FT or digital
      method of IOP estimation remains useful for detecting elevated IOP early after
      corneal transplantation if the proper technique is used and substantial lid edema
      and patient discomfort are absent.

PMID- 9547776
TI  - The "deroofing" of Schlemm's canal in patients with open-angle glaucoma through
      placement of a collagen drainage device.
AB  - BACKGROUND AND OBJECTIVES: A preliminary study was conducted to examine a new
      surgical approach for the management of patients with open-angle glaucoma in
      which Schlemm's canal is opened to restore drainage in a nonpenetrating fashion.
      The authors compared the results of the surgical procedure including the new
      glaucoma drainage device with the results of standard trabeculectomy. PATIENTS
      AND METHODS: The authors performed a new type of surgical procedure on 58
      consecutive patients with open-angle glaucoma. The procedure entails "deroofing"
      Schlemm's canal to facilitate the drainage of aqueous without penetrating the
      eye. This is done by exposing the canal after a partial-thickness sclerectomy and
      keratectomy along a 5-mm arc. After the canal was deroofed, a new type of
      collagen glaucoma drainage device was placed in the surgical site to maintain
      drainage postoperatively. Patient data, including intraocular pressure (IOP),
      complications, and the number of medications required to maintain adequate
      pressures, were analyzed for 1 year postoperatively. RESULTS: Within 1 to 2
      months postoperatively, 80.9% of the patients achieved an IOP lower than 21 mm
      Hg. This improved to 88.9% at 3 to 6 months postoperatively and 87.5% at 6 to 12
      months postoperatively. The only major complications were microperforations
      (8.6%) related to surgical technique and a few cases of high IOP that required
      repeat operations (10.3%). CONCLUSIONS: The nonpenetrating technique for
      deroofing the canal effectively allows the drainage of aqueous to acceptable
      levels (in the range of 15 to 17 mm Hg) without the complications associated with
      penetrating trabeculectomy. Complications are rare, and the collagen drainage
      device appears to be effective for allowing the drainage site to remain patent
      after its dissolution.

PMID- 9547777
TI  - Phacotrabeculectomy: comparison of results from 3.5- and 5.2-mm incisions.
AB  - BACKGROUND AND OBJECTIVE: To compare the intraocular pressure control, visual
      results, and astigmatic results of 3.5-mm and 5.2-mm incisions following
      phacotrabeculectomy with 12 months of follow-up. PATIENTS AND METHODS: Fifty eyes
      underwent clear cornea punch trabeculectomy under a 5.0 x 2.5-mm scleral flap,
      closed with two 10-0 polyglactin sutures. The first 25 eyes underwent wound
      extension to 5.2 mm for insertion of a single-piece polymethylmethacrylate (PMMA)
      lens. The next 25 eyes underwent wound extension to 3.5 mm for insertion of a
      folded silicone lens. RESULTS: The mean intraocular pressure decrease from the
      preoperative level was 7.6 mm Hg in the 3.5-mm incision group and 7.8 mm Hg in
      the 5.2-mm incision group. One patient required continued medication. The best
      corrected visual acuity was 20/40 or better in 86% of the patients, with no
      significant difference between the groups. The mean "with the wound" induced
      astigmatism showed no statistical difference between the two groups. CONCLUSIONS:
      The use of 10-0 polyglactin appears to aid filtration, yet minimizes hypotony or
      the need for antimetabolites. For surgeons who wish to reduce costs without
      compromising results during phacotrabeculectomy, there is merit in considering a
      5.2-mm incision; moreover, the more rigid single-piece PMMA lens appears to be
      associated with fewer complications in the immediate postoperative period.

PMID- 9547778
TI  - Subretinal semiconductor microphotodiode array.
AB  - BACKGROUND AND OBJECTIVE: To examine the function of a semiconductor
      microphotodiode array (SMA) surgically implanted in the subretinal space.
      MATERIALS AND METHODS: Positive-intrinsic layer-negative (PiN) or negative
      intrinsic layer-positive (NiP) SMAs were surgically placed into the subretinal
      space of rabbits through a pars plana incision and a posterior retinotomy. The
      implants required no external connections for power and were sensitive to light
      over the visible and infrared (IR) spectrum; IR stimuli were used to isolate
      implant-mediated responses from the activity of native photoreceptors. A
      stimulator ophthalmoscope was used to superimpose IR stimuli on the implant and
      adjacent retinal areas, and responses were recorded during the postoperative
      recovery period. SMA responses were also evaluated in vitro. The animals were
      given lethal anesthetic overdoses, and the retinas were examined histologically.
      RESULTS: The in vitro implant response consisted of an electrical spike, followed
      by a small-amplitude DC offset that followed the time course of the IR
      stimulation, and an overshoot at the stimulus offset. The SMAs placed in the
      subretinal space retained a stable position and continued to function throughout
      the postoperative period. The SMA responses recorded in vivo included additional
      slow-wave components that were absent from the in vitro recordings. These
      responses reverted to the in vitro configuration following the death of the
      animal. There was a significant loss of retinal cells in areas overlying the
      implant, and the retina appeared normal away from the implant and surgical site.
      CONCLUSION: SMAs can be successfully implanted into the subretinal space and will
      generate current in response to light stimulation during an extended period of
      time.

PMID- 9547779
TI  - Chorioretinal folds following glaucoma valve implantation.
AB  - Glaucoma valve implants have been observed to cause scleral indentation and
      flattening. The authors report the case of a 79-year-old woman who had previously
      undergone glaucoma valve implantation, and who subsequently developed
      chorioretinal folds that corresponded to the implant in location and
      configuration. Accumulation of fluid behind the implant, as documented by B-scan
      ultrasonography, appeared to result in the observed scleral and chorioretinal
      changes. The authors conclude that chorioretinal folds can result following
      glaucoma valve implantation.

PMID- 9547781
TI  - Delayed-onset expulsive choroidal hemorrhage following traumatic globe rupture.
AB  - The authors describe a 59-year-old woman who had a traumatic wound rupture 6
      months following penetrating keratoplasty. While she was in the pre-operative
      holding area awaiting surgical repair, hemorrhagic choroidal detachments
      developed. Digital pressure was initiated on diagnosis of imminent expulsion of
      intraocular contents and maintained until repair of the wound rupture could be
      performed. Four months postoperatively, the patient's vision was 20/80 and her
      central pachymetry was 585 microns. This case demonstrates that a delayed-onset
      expulsive choroidal hemorrhage may be successfully managed with simple and rapid
      intervention based on knowledge of the disease process.

PMID- 9547780
TI  - The use of pneumatic retinopexy to delay surgical repair of a retinal detachment
      associated with the ganciclovir intraocular device.
AB  - Rhegmatogenous retinal detachments are associated with cytomegalovirus (CMV)
      retinitis and the use of the ganciclovir intraocular device. Pars plana
      vitrectomy with silicone oil tamponade is the preferred technique to repair such
      detachments. The authors describe the use of pneumatic retinopexy as part of a
      treatment strategy in the management of multiple retinal detachments in a patient
      with CMV retinitis treated with ganciclovir implants. Pneumatic retinopexy may
      benefit patients when the causative retinal break is superior and is located in
      an area of retina uninvolved with CMV infection, because it can be used to delay
      surgical intervention.

PMID- 9547783
TI  - Dislocation of the mandible during the course of cataract surgery.
AB  - Spontaneous dislocation of the mandible is a well-described clinical entity with
      which the ophthalmologist may not be familiar. However, the widespread use of
      intravenous sedation places susceptible individuals at risk for the development
      of dislocation of the mandible. The authors describe a patient who underwent
      routine cataract surgery and suffered a dislocation of the mandible that
      initially went unrecognized. Ophthalmic surgeons who use intravenous sedation
      need to be aware of this complication and need to recognize the symptoms so that
      patients may receive timely attention.

PMID- 9547782
TI  - Monopolar electrosurgical flash fire.
AB  - A 78-year-old man underwent ectropion repair with a monopolar electrosurgical
      unit. A flash fire occurred, resulting in a loss of eyelashes of the left upper
      and lower eyelids. A retrospective analysis of the case was conducted, including
      a review of the relevant literature. Although rare, the possibility of a flash
      fire should be considered when performing surgery with an electrosurgical unit.
      Minimizing supplemental oxygen and electrosurgical power settings may help to
      avoid such an incident.

PMID- 9547784
TI  - A simple, cost-effective method for practicing phacoemulsification in the
      cadaveric eye.
AB  - The authors describe an inexpensive, reliable method for practicing intraocular
      surgery using a rigid contact lens as a temporary keratoprosthesis. This method
      allows clear visualization of the anterior chamber and lenticular structures for
      practicing modern cataract surgery, including capsulorhexis, hydrodissection,
      phacoemulsification, cortical aspiration, and intraocular lens insertion.

PMID- 9547785
TI  - Localized delivery of anti-cancer drugs by electroporation.

PMID- 9547786
TI  - Yeast arrays join the search for specific drugs.

PMID- 9547787
TI  - A molecular basis for sudden infant death syndrome.

PMID- 9547788
TI  - New strategies to combat fungal infections.

PMID- 9547789
TI  - Animal cell technology for new healthcare products. 15th European Society for
      Animal Cell Technology (ESACT) meeting. Tours France 7-11 September 1997.

PMID- 9547790
TI  - Transplantation biology: recent advances. 5th basic sciences symposium of the
      Transplantation Society. Chautauqua, NY, USA, 6-11 September 1997.

PMID- 9547791
TI  - The Human Genome Diversity Project: medical benefits versus ethical concerns.
AB  - By the year 2005 the entire human genome should have been sequenced and the genes
      identified. But the resulting genomic sequence, although a marvelous
      accomplishment, will be a composite of just a handful of individuals selected at
      random. The Human Genome Diversity Project was proposed as a means to overcome
      these limitations by obtaining genetic information from many diverse populations
      of the world. This would give medical geneticists a handle on the variations in
      susceptibility to disease among different populations, as well as being of
      anthropological value. But would such a project risk exploiting the indigenous
      populations involved?

PMID- 9547792
TI  - Immune evasion by tumours: involvement of the CD95 (APO-1/Fas) system and its
      clinical implications.
AB  - T cells can cause the death of tumour cells by two mechanisms, one involving CD95
      and the other involving perforin. T-cell activity or reduced tumour-cell
      responsiveness towards CD95 stimulation might result in an impaired anti-tumour
      immune response and tumour cell outgrowth. Recent data suggest that de novo
      expression of the CD95 ligand (CD95L) in tumours might result in elimination of
      CD95+ anti-tumour lymphocytes, and that tumours might therefore be privileged
      sites. However, conflicting data on the role of CD95L in transplantation
      experiments indicate that CD95L expression alone might not be sufficient to
      confer the status of immune privilege.

PMID- 9547793
TI  - Regulation of cardiovascular collagen deposition by mechanical forces.
AB  - Collagen is a vital component of the extracellular matrix of both the heart and
      blood vessel walls. It acts as a scaffold to maintain myocardial shape and permit
      an even distribution of force, and plays a crucial role in the mechanical
      properties of the blood vessels. Under normal circumstances, collagen is
      continually being synthesized and degraded throughout life. Increased mechanical
      stress, which causes myocardial hypertrophy and vessel wall thickening,
      stimulates collagen turnover. If collagen is deposited in excess (fibrosis),
      tissue function can be compromised. An understanding of the mechanisms of
      'mechanosignal transduction' involved in this process will enable therapeutic
      approaches to be devised that will prevent inappropriate collagen deposition and
      thereby help to preserve function.

PMID- 9547794
TI  - Antibodies to OX-40 (CD134) can identify and eliminate autoreactive T cells:
      implications for human autoimmune disease.
AB  - Autoantigen-specific CD4+ T cells have been implicated as the causative cell type
      in: multiple sclerosis, rheumatoid arthritis, autoimmune uveitis, diabetes
      mellitus, inflammatory bowel disease and graft-versus-host disease. The pathology
      of a number of experimentally induced autoimmune diseases is also mediated by
      autoantigen-specific CD4+ T cells. Ideally, treatment of CD4+ T-cell-mediated
      diseases would eliminate the autoantigen-specific cells, while sparing the
      remainder of the T-cell repertoire. We have developed an effective therapy that
      deletes the autoreactive T cells at the site of autoimmune tissue destruction.
      This approach uses an antibody directed against a cell-surface protein (OX-40,
      also known as CD134) that is selectively upregulated on activated autoantigen
      specific T cells within the inflamed tissue.

PMID- 9547796
TI  - Is routine dilation a waste of time?

PMID- 9547795
TI  - Strategies for achieving multiple layers of selectivity in gene therapy.
AB  - Here we review the progress towards the development of targeted vectors for
      direct in vivo delivery in gene therapy. Currently, there are many separate
      approaches. These include: simple physical/anatomical localization of
      administration of the vector at the site where gene transfer is required;
      exploitation of natural tropisms of plasmid, viral and cellular vectors; and the
      use of molecular engineering to change the specificity of proteins and nucleic
      acids so that they specifically recognize target ligands expressed on/in the
      target cells. Unfortunately, each of these approaches is usually imperfect by
      itself. However, combinations of these strategies might produce vectors in which
      several layers of imperfect targeting give an overall level of specificity that
      can justify systemic delivery of vectors to treat human disease.

PMID- 9547797
TI  - Free-floating vitreous cyst.
AB  - Cysts of the vitreous are an unusual clinical finding, with only about 50 such
      cases reported in the literature. The sizes of the cyst may vary from 0.15 to 12
      mm, and they have been found in the anterior and posterior vitreous. The etiology
      has been theorized to be both congenital and acquired. Acquired cysts may be due
      to trauma or other forms of intraocular inflammation. Pigmented cysts are
      believed to originate from the pars ciliaris and nonpigmented cysts are likely to
      be derived from the remnants of the hyaloidal artery system. The appearances of
      the cysts are striking and are often seen as clear spherical bodies in the
      vitreous with interesting interlacing surface patterns. The cysts are benign and
      are of little significance, except when they encroach on the visual axis and
      produce visual disturbances (usually floater symptoms).

PMID- 9547798
TI  - Visual correlates of obstacle avoidance in adults with low vision.
AB  - This study examined how mobility performance in a heterogeneous sample of
      visually impaired adults relates to measures of visual sensory and perceptual
      function. We found that the best predictors of mobility performance under
      photopic and scotopic lighting conditions were models that incorporated visual
      field extent (VFE) and scanning ability. Together with measures of contrast
      sensitivity and spatial resolution, these models accounted for approximately 50%
      of the variance in mobility performance. We also found that VFE and scanning
      ability were the dominant predictor variables when the sample was broken down by
      subjects' type of vision loss into an acuity loss, a visual field restriction,
      and a combination loss group.

PMID- 9547799
TI  - Psychophysics of reading. XVII. Low-vision performance with four types of
      electronically magnified text.
AB  - Most people with low vision need magnification to read. Page navigation is the
      process of moving a magnifier during reading. Modern electronic technology can
      provide many alternatives for navigating through text. This study compared
      reading speeds for four methods of displaying text. The four methods varied in
      their page-navigation demands. The closed-circuit television (CCTV) and MOUSE
      methods involved manual navigation. The DRIFT method (horizontally drifting text)
      involved no manual navigation, but did involve both smooth-pursuit and saccadic
      eye movements. The rapid serial visual presentation (RSVP) method involved no
      manual navigation, and relatively few eye movements. There were 7 normal subjects
      and 12 low-vision subjects (7 with central-field loss, CFL group, and 5 with
      central fields intact, CFI group). The subjects read 70-word passages at speeds
      that yielded good comprehension. Taking the CCTV reading speed as a benchmark,
      neither the normal nor low-vision subjects had significantly different speeds
      with the MOUSE method. As expected from the reduced navigational demands, normal
      subjects read faster with the DRIFT method (85% faster) and the RSVP method
      (169%). The CFI group read significantly faster with DRIFT (43%) and RSVP (38%).
      The CFL group showed no significant differences in reading speed for the four
      methods.

PMID- 9547800
TI  - Benefits of rapid serial visual presentation (RSVP) over scrolled text vary with
      letter size.
AB  - We previously reported that low vision readers do not benefit from a rapid serial
      visual presentation (RSVP) display relative to a scroll display. Each reader in
      those studies was presented with only one letter size, and it was the same for
      both displays. In the current study, we systematically varied the size of the
      letters and compared reading rates from the 2 displays for letters that were 2,
      4, 6, 8, and 10 times each reader's acuity threshold. Using this paradigm, we
      found that subjects with normal vision (n = 12) read faster with RSVP for all
      text sizes. Low vision subjects (N = 20) showed no benefit of RSVP until the text
      was at least 8x their acuity threshold. As in our prior studies, there was a
      great deal of variability within the low vision group, and for a small number of
      subjects (25%), reading was faster from the scroll than from the RSVP display.

PMID- 9547801
TI  - Corneal aberrations, monocular diplopia, and ghost images: analysis using corneal
      topographical data.
AB  - Corneal irregularities can create conditions in which monocular diplopia, "ghost
      images," and multiple images of various types occur, thus degrading vision. For
      these secondary images to occur, corneal irregularities must create areas which
      form: (1) images which are displaced from the primary image; (2) sufficiently
      focused images; and (3) images which have sufficient contrast to be noticed in
      the presence of the primary image. Criteria necessary to satisfy these three
      conditions using measurable data are developed. The concept of a differential
      deflection field is introduced, and a method to create this field using corneal
      topography data is developed. It is shown how to use differential deflection
      field data to assess if conditions necessary for creating secondary images will
      occur in cases of corneal distortion.

PMID- 9547802
TI  - Validating a "pillar and collar" technique for measuring the edge lift of rigid
      contact lenses.
AB  - PURPOSE: The clinical importance of the edge lift of rigid contact lenses is
      often neglected, possibly due to previous difficulties in its measurement. A new
      method of measuring axial edge lift (AEL) and radial edge lift (REL) using
      standard contact lens verification equipment, such as an optical spherometer, a
      thickness gauge, and contact lens V gauge, is described. METHODS: The technique
      was validated for trueness (accuracy) and precision (repeatability) by measuring
      the edge lift of a number of monocurve lenses, manufactured both with and without
      a normal edge finish. RESULTS: Edge lift was measured to an accuracy of 0.01 mm.
      CONCLUSIONS: As long as a mean of eight independent measurements of back optic
      zone radius (BOZR), sagitta, and one measurement of center thickness are taken,
      the pillar and collar technique is capable of producing accurate and repeatable
      measurements of the edge lift of a rigid contact lens.

PMID- 9547803
TI  - "Pillar and collar" technique for measuring the axial edge lift of multicurve
      rigid lenses.
AB  - BACKGROUND: The method of using an optical spherometer and a lens thickness
      gauge, in combination with a pillar and collar, has previously been shown to be
      repeatable and accurate (to 0.01 mm) in measuring the edge lift of rigid
      monocurve lenses. PURPOSE: This paper goes on to validate the technique for
      measurements taken on edge-finished multicurve rigid lenses. METHODS: The axial
      edge lift (AEL) of a series of multicurve rigid lenses having known values of AEL
      was measured using an optical spherometer, a thickness gauge, and contact lens V
      gauge in a similar way as was described in the companion paper. RESULTS: The
      results show that as long as a correction factor of 0.01 mm is applied, as found
      in the previous paper, the technique will allow satisfactory verification of the
      edge lift. CONCLUSIONS: The technique is accurate and reproducible, even in
      multicurve lens designs, provided that a calibrating correction factor of 0.01 mm
      is applied to account for methodological error. It will also indirectly allow the
      accuracy of manufacture of the peripheral curves and diameters of any rigid
      contact lens to be verified.

PMID- 9547804
TI  - Influences of the accommodative stimulus and aging on the accommodative
      microfluctuations.
AB  - The effects of the accommodative stimulus and age on the accommodative
      microfluctuations were investigated in human subjects. Accommodative responses
      were measured by using an infrared (IR) optometer, and accommodative
      microfluctuations were quantified by power spectrum analysis. Two frequency bands
      were determined: low frequency components (< 0.5 Hz, LFC) and high frequency
      components (1.3 to 2.2 Hz, HFC). Among younger subjects, the changes in the HFC
      in response to the accommodative stimuli differed between subjects. The activity
      of the HFC reached a peak in the center of the accommodation range, whereas the
      activity of the LFC was its maximum in the presence of darkness or blur in the
      over-accommodation range. Smaller changes in the magnitude of the HFC were
      observed in older subjects. Although the LFC may be controlled neurologically,
      the HFC seems to arise from mechanical and elastic properties of the lens, and
      may be modulated by other physiological rhythmic variations.

PMID- 9547805
TI  - Influence of spatial distribution with blur on fluctuations in accommodation.
AB  - PURPOSE: We investigated the influence of spatial distribution of retinal image
      with blur on the waveform of microfluctuations in accommodation. METHODS: We
      studied changes in accommodation in 8 young emmetropic subjects (21.88 +/- 2.36
      years old), who viewed monocularly a target with the natural pupil. The spatial
      frequency of the target was varied from 0.85 to 15 cpd in 7 steps, and the blur
      intensity was increased in 7 steps to obtain a Gaussian distribution of retinal
      image. Continuous accommodation signals were recorded using an eye-tracking
      infrared optometer with a sampling frequency of 40.98 Hz, and analyzed with a
      fast Fourier transform (FFT) analyzer. The power spectra of the low frequency
      component (LFC, < 0.6 Hz) and the high frequency component (HFC) at approximately
      1.9 Hz were calculated for each target with a frequency resolution of 0.02 Hz.
      RESULTS: Microfluctuations in accommodation increased as the blur was increased
      and decreased at further increases in blur intensity level. Microfluctuations
      peaked at a lower blur level as the spatial frequency was increased. Power
      spectral analysis revealed that these changes in the microfluctuations could be
      attributed mainly to increases of power in the LFC. CONCLUSIONS: Blurring of the
      edge and reduction in contrast provided accommodative cues, inducing
      microfluctuations in accommodation, and the LFC increased as the target sharpness
      was reduced, possibly in an attempt by the accommodation system to maintain the
      sharpness of the retinal image under poor stimulus conditions. However, when the
      blur level was increased, the amount of blur was indistinguishable and
      microfluctuations in accommodation decreased.

PMID- 9547807
TI  - Freeze-dried cortical allografts.

PMID- 9547806
TI  - Broken intramedullary femoral nail.

PMID- 9547808
TI  - Consumers losing confidence in managed care.

PMID- 9547809
TI  - The effect of partial lateral meniscectomy in patients > or = 60 years.
AB  - To determine the benefit, if any, of meniscectomy in an older population, all
      patients > or = 60 years who underwent partial lateral meniscectomy were
      evaluated. Thirty-five patients (36 knees) were available for follow-up. The
      average patient age was 64.9 years. Patients were divided into two groups based
      on the degree of articular cartilage damage. Patients in group 1 had no damage
      worse than grade II and underwent arthroscopic partial meniscectomy only, while
      patients in Group 2 had grade III or IV damage and underwent arthroscopic
      debridement as well as partial meniscectomy. With an average follow-up of 36.8
      months, the overall failure rate was 13.9%. Eighty-six percent of the patients
      reported the overall assessment of their knee as improved (94% and 80% in groups
      1 and 2, respectively). While patients in group 2 tended to have less favorable
      results than patients in group 1, these results indicate that this procedure is
      warranted and that both groups benefited significantly from partial meniscectomy.

PMID- 9547810
TI  - Side effect of ibuprofen and valproic acid.

PMID- 9547811
TI  - Post-traumatic heterotopic ossification about the elbow.
AB  - To evaluate the effect of surgical timing on the formation of heterotopic
      ossification about the elbow, 71 consecutive patients with elbow trauma requiring
      operative management were evaluated. Fourteen patients were excluded because they
      suffered from head injury, burns, or severe open injuries requiring surgery on
      two or more occasions. Sixteen patients were lost to follow-up, leaving a group
      of 41 patients. The average age of patients was 35 years. The fractures involved
      the olecranon in 19, distal humerus in 12, and radial head/neck in 10 patients.
      Six of these fractures were accompanied by a dislocation. Eleven were open
      injuries; the remaining 30 were closed. Bone grafting was performed in nine
      patients. The interval between injury and surgical intervention averaged 57
      hours. None (0%) of 17 patients treated within 48 hours developed grade II, III,
      or IV heterotopic ossification, whereas 8 (33%) of 24 patients treated after 48
      hours developed grade II, III, or IV heterotopic ossification. There were no
      significant differences in demographic or injury parameters between these two
      groups. These findings suggest that fixation of unstable elbow fractures within
      48 hours of injury may reduce the formation of ectopic bone.

PMID- 9547812
TI  - The Richards Series 2 total hip prosthesis: a 13-year study and radiographic
      evaluation.
AB  - This retrospective long-term study analyzes the clinical function, failures, and
      radiographic status of 131 Richards Series 2 prostheses in total hip
      arthroplasties (THAs) performed during 1981 and 1982. After a minimum follow-up
      period of 11 years, the results were evaluated. Sixty two (54%) patients with 71
      THAs were available for follow-up; 44 (38%) patients with 49 THAs had died. Three
      patients with three THAs were lost to follow-up, and seven patients with eight
      THAs were unable to participate in the examination due to causes not related to
      their present hip status. Ten patients underwent revision THA during the
      observation period. The median hip functional index (HFI) was 8.6 preoperatively
      and 15.8 at follow-up. Hip functional index correlated to radiographic signs of
      loosening. With revision as endpoint, the Kaplan-Meier survivorship for all 131
      hips was 93% after 10 years and 91% after 12 years. The radiographic examination
      at follow-up revealed 5 (8%) definite loose cups and 12 (19%) definite loose
      stems. Including the number of aseptic loosened cups and stems confirmed at
      revision, aseptic loosening was found in 6% of all cups and 13% of all stems.
      This radiographic evaluation confirmed that lack of containment of the cup and
      varus position of the stem were factors influencing the long-term stability of
      the prostheses, whereas etiology, type of arthritis, and ectopic ossification did
      not. A fixation and stability score that was modified for cemented prostheses was
      developed and was of value in detecting the prostheses at risk. The long-term
      results of the Richards Series 2 THA are acceptable and comparable with other
      long-term studies on conventional prosthetic designs. Ten percent to 20% revision
      THAs due to aseptic loosening can be expected. In addition, patients younger than
      age 60 at surgery and especially men were found to belong to a high-risk group
      with regard to revision THA. These patients must be evaluated carefully so that
      revision THA can be performed before the bone bed is destroyed.

PMID- 9547813
TI  - Comparison of fixation methods for preventing pelvic ring expansion.
AB  - Several methods of external and internal fixation are used in urgent situations
      to lessen intrapelvic bleeding associated with unstable pelvic fractures. Pelvic
      stabilization limits pelvic expansion and thereby restricts the space for
      potential blood loss. This study compared several fixation methods using
      cadaveric pelves to determine which method best prevents pelvic expansion. Three
      methods of internal fixation and three methods of external fixation were
      compared. Anteroposterior fixation provided the greatest control against pelvic
      expansion; however, it is clinically impractical for emergency use. Therefore,
      external fixation provided the most reliable control of pelvic expansion in the
      emergency setting.

PMID- 9547814
TI  - The effects of pulsed electromagnetism on fresh fracture healing: osteochondral
      repair in the rat femoral groove.
AB  - Some clinical studies have claimed significant reductions in the healing time of
      fresh fractures with the use of pulsed electromagnetic fields (PEMFs). Animal
      models, however, have produced more equivocal results. This investigation
      examined the effects of PEMF treatment on an osteochondral defect placed in the
      patellofemoral groove of the rat. The results indicated that PEMF enhances early
      vascular reaction and suppresses initial pannus proliferation. Early
      chondrogenesis and bone formation were consistently stimulated, and the
      restoration of normal bone trabeculae advanced. Pulsed electromagnetic field
      treatment therefore may be useful in advancing repair during the early
      proliferative stage. Later results were variable and suggest that prolonged use
      may have deleterious effects, enhancing chondrogenesis beyond a point observed in
      normal repair and thus delaying normal subsurface trabeculation.

PMID- 9547815
TI  - Functional distal interphalangeal joint splinting for trigger finger in laborers:
      a review and cadaver investigation.
AB  - This two-part study evaluates the efficacy of functional distal interphalangeal
      joint (DIP) splinting for the treatment of trigger finger. Thirty-one fingers
      from 21 meat packing plant workers were treated with DIP splinting. A single
      corticosteroid injection was offered if triggering was stage 4 or greater. All
      workers returned to work immediately. Eighty-one percent of the digits were
      treated successfully (mean follow-up: 1 year). Treatment failure correlated with
      duration of symptoms and stage of triggering but did not correlate with age,
      race, sex, disease in multiple digits, or prior treatment. For the second part of
      the study, the effect of DIP splinting on flexor digitorum profundus (FDP) tendon
      excursion was studied in 16 fingers from 4 fresh cadavers. Excursion decreased
      4.8 mm for the Stax splint and 4.2 mm for the dorsal Alumafoam splint. We
      conclude that DIP splinting provides a reliable and functional means of treating
      work-related trigger finger without lost time from work. Our cadaver
      investigation supports our theory that DIP splinting significantly decreases FDP
      excursion.

PMID- 9547816
TI  - Newborn clavicle fractures.
AB  - A prospective screening program of 9106 newborns identified 43 infants with
      clavicle fractures for a prevalence of 1 fracture in every 213 live births
      (0.5%). The fractures were equally distributed by right and left side
      involvement, and male and female sex. All fractures occurred during vaginal
      deliveries. None were breech presentation. Risk factors for fracture included
      large birth-weight, shoulder dystocia, mechanically assisted delivery, and
      prolonged gestational age. One in 11 newborns with a clavicle fracture also had a
      brachial plexus palsy.

PMID- 9547817
TI  - Revision arthroplasty of femoral cortex defect using a noncemented stem, Mennen
      plate, and bone graft.
AB  - Twelve patients who underwent total hip replacement complicated by aseptic
      loosening with severe bone loss were included in this study. Two patients had
      aseptic loosening of the second revision, six of the third revision, and the
      remaining four patients of the fourth revision total hip replacement. In all
      patients, the radiographs revealed an extremely thin cortex around the stem of
      the prosthesis and almost complete disappearance of one cortex. All patients were
      treated by revision total hip replacement in conjunction with Mennen plate
      fixation and allograft bone support. The allograft bone support included three
      cortical struts and nine massive bone grafts that used cement as a strew. The
      results were satisfactory in 10 patients in respect to functional activity, pain
      and radiographic evaluation. In two patients who underwent their fifth revision,
      the results were unsatisfactory but better than before the operation. Mennen
      plate fixation provides a sufficient and easy technique for aseptic loosening of
      total hip replacement with severe bone loss. By preserving the periosteal blood
      supply, the time required for bone graft incorporation is shortened, resulting in
      an early final outcome.

PMID- 9547818
TI  - The location of the spinal nerve root on plain radiographs of the cervical spine.
AB  - Twelve cervical spines from C2 to T1 were harvested from embalmed cadavers to
      study the location of the nerve root on plain radiographs. After removal of the
      soft tissue, the spinal nerves just lateral to the transverse processes were
      exposed and injected with lead oxide. Plain radiographs including anteroposterior
      (AP) and left and right oblique views were taken. Angular and linear measurements
      were performed directly on the radiographs. Results showed that the average
      frontal angle of the nerve root for all levels was 155 degrees on the AP view,
      108 degrees on the foraminal side of the oblique view, and 153 degrees on the
      opposite side of the oblique view. The nerve root height for all levels averaged
      4.7 +/- 0.5 mm. The interpedicular space height increased consistently from 7.8
      +/- 0.7 mm at C3-C4 to 9.0 +/- 1.3 mm at C6-C7 except at C2-C3. The nerve root
      height with respect to the interpedicular space height was 56.2% at C2-C3, 57.8%
      at C4-C5, and 53.7% at C6-C7. A knowledge of the location of the cervical nerve
      root related to plain radiographs may enhance the value of plain radiographs in
      the diagnosis and treatment of cervical spinal disorders.

PMID- 9547819
TI  - Limb salvage versus amputation for severe open fractures of the tibia.

PMID- 9547820
TI  - Osteoblastoma of the acetabulum.

PMID- 9547822
TI  - An unusual presentation of locked knee.

PMID- 9547821
TI  - Recurrent osteochondromatosis of the shoulder in a child.

PMID- 9547823
TI  - Nonunion of the radial neck following fracture of the radial head and neck: case
      reports and a review of the literature.

PMID- 9547824
TI  - Carpal tunnel syndrome associated with eosinophilic fasciitis.

PMID- 9547825
TI  - Primary proximal row carpectomy.

PMID- 9547826
TI  - Radiologic case study. Osteochondritis dissecans.

PMID- 9547827
TI  - A possible defective estimation of antineutrophil cytoplasmic antibodies in
      systemic lupus erythematosus due to the coexistence of periodontitis: preliminary
      observations.
AB  - The objectives of this study is to determine if periodontitis-related ANCA hinder
      the accurate estimation of this kind of autoantibodies in systemic lupus
      erythematosus (SLE), due to the frequent coexistence of SLE and periodontitis,
      and the high incidence of antineutrophil cytoplasmic antibodies (ANCA) in this
      periodontal condition. Thirty SLE, thirty periodontitis lacking systemic
      involvement patients, and twenty healthy controls were utilized in this study.
      The periodontal condition and the presence of ANCA in sera of all individuals was
      carefully evaluated. For ANCA determination an EIA assay was utilized, directed
      to a neutrophil granular extract and six neutrophil granule proteins. Sixty
      percent of SLE patients had periodontitis, and sixty-five percent were ANCA
      positive. Eighty three percent of all ANCA cases were coexisting with
      periodontitis. A significant association (p > 0.005) between periodontitis and
      ANCA was found (Chi Square Test). Fifty percent of the patients with
      periodontitis lacking systemic involvement were ANCA positive. The results
      obtained in this study suggest that the figures of ANCA previously reported for
      SLE, might be overestimated due to the inadvertent presence of periodontitis.

PMID- 9547828
TI  - Early detection of depression using the Zung Self-Rating Depression Scale.
AB  - OBJECTIVE: Compare the findings of the application of the Zung self-rating
      depression scale to spanish community during the NDSD on three consecutive years
      (1993, 1994, 1995). METHOD: 630 adults in a spanish community filled out the Zung
      Self Rating Depression Scale (spanish translation) during the NDSD in october
      1993, 1994, 1995. The responders were oriented regarding the results and clinical
      implications. Scale results were entered on epi-info 6.0 for statistical
      analysis. RESULTS: The obtained data shows a female preponderance in all samples.
      The groups found with SDS compatible with severe to extreme depression were 9.2%,
      9.3 and 11.3% for the respective years. Symptoms more significantly reported by
      the responders with a SDS of 50 or more were psychomotor retardation, confusion
      and anhedonia. Suicidal ideations were reported in 17.8% (1993), 15.5% (1994) and
      20.7% (1995) of the sample. CONCLUSION: Despite the limitations of this study the
      results suggest that the Zung self-rating depression scale can be helpful in the
      early detection of depression in patients seen in their initial evaluation by the
      primary care physician. It's usefulness with spanish speaking communities at
      other clinical settings should be assessed more extensively.

PMID- 9547829
TI  - Dietary analysis of meals served in the breakfast and lunch programs of Puerto
      Rican schools.
AB  - BACKGROUND: Nutritional analysis of meals in the Federally-sponsored Breakfast
      and Lunch Programs in Stateside Schools has recently been completed. However due
      to ethnic and cultural differences, the findings may not be directly applicable
      to similar nutrition programs in Puerto Rico. It is our aim to carry out an
      analysis of meals served in Federal programs in Puerto Rico and to compare
      results to the stateside study. METHODS: Twenty eight different breakfast meals
      and 96 different lunch meals being cycled in elementary, middle and secondary
      schools throughout the entire island of Puerto Rico were analyzed for content
      using the Minnesota Nutrition Data System 32 and compared with: 1) compliance to
      meal pattern requirements of federal programs, 2) dietary guidelines for
      Americans (DG) and 3) recommended dietary allowances (RDA's). RESULTS: Breakfasts
      and lunches served in Puerto Rican Schools satisfy federal meal pattern
      requirements however most frequently offered foods different from programs in the
      mainland, reflecting ethnic and cultural food preferences. In terms of DG's
      adequate protein was present, cholesterol content was satisfactory but meals had
      excess percent energy from fat as well as excess energy from saturated fat, high
      sodium and a lower than recommended level of energy from carbohydrate. In terms
      of RDA's meals had prescribed levels of vitamin A, vitamin B12, vitamin C,
      calcium, folacin, magnesium, phosphorus and potassium. Below prescribed levels
      included vitamin B6, copper, vitamin E, energy, fiber, iron, niacin and zinc.
      CONCLUSIONS: While differences in food preferences exist between foods available
      in the Breakfast and Lunch Programs in Puerto Rican and U.S., schools, they have
      similar strengths and weaknesses when compared to compliance with U.S. Dietary
      Guidelines and with recommended dietary allowances.

PMID- 9547830
TI  - Folate supplementation and neural tube defects: a review of a public health
      issue.
AB  - Folate deficiency is one of today's most common vitamin deficiencies in women.
      Women who consume a low level of folate during pregnancy are at risk for poor
      pregnancy outcomes including neural tube defects (NTD). However, other factors
      such as heredity, social class, maternal age, birth order, maternal diet, length
      of time between pregnancies, maternal zinc deficiency, use of anticonvulsant
      drugs, abnormal homocysteine metabolism and the use of oral contraceptives, have
      also been implicated as causes of NTD. Animal studies have shown that fetuses are
      highly dependent on the folate status of the mother. In addition, several
      retrospective and prospective human studies have provided evidence that folate
      lowers the incidence of NTD.

PMID- 9547831
TI  - Cesarean childbirth in Puerto Rico: the facts.
AB  - According to the last Island-wide survey carried out in 1982 in Puerto Rico, the
      cesarean rate for the trienium of 1980-82 was estimated in 27 percent. Since
      1989, an item about the type of delivery has been included in the live birth
      certificate. These data indicate that the incidence of cesarean deliveries
      continued to increase and by 1994 it amounted to 31 percent, undoubtedly the
      highest rate of the world. However, its fluctuation since 1990 suggests that this
      type of delivery has finally steadied in Puerto Rico. The high proportion of
      repeated cesareans and the low percentage of vaginal birth after cesarean (VBAC)
      deliveries were important factors contributing to the overall rate. Unexpectedly
      high risk mothers such as, adolescents, unwed and those of the lower
      socioeconomic status had highest cesarean rates than their encounterparts.
      Similarly, mothers who had the most adequate prenatal care had the highest
      percentages of surgical deliveries. In spite of dealing with a selected
      clientele, the cesarean rate in private hospitals was more than twice that of
      public institutions. In fact, a multiple correlation analysis demonstrate that
      the type of hospital of delivery was the most important correlate of a cesarean.

PMID- 9547832
TI  - [Women abandoned by Social and Health Agencies. Challenge in the prevention of
      HIV/AIDS].
AB  - The present study examined the role of an intervention directed to link a group
      of sexual workers with social and health services. The subjects receptivity to
      use these services was measured by the degree of acceptance that the selected
      agencies provided to the participants of this study. The present investigation
      included two groups of subjects consisting of sexual workers and other women that
      were at high risk of prostitution because of their social circumstances. The
      sample consisted of 92 women residents of either the San Juan area of other towns
      from the eastern part of Puerto Rico. The method of focal group and a agencies
      directory was utilized during the intervention. In addition, the attempt to
      establish a helpful relationship between the subject and the agency was also
      incorporated to the investigation. The present findings showed the presence of a
      considerable social distance between the agencies and the subjects studies. The
      use of the studied intervention failed to be an efficient strategy. The authors
      recommend to explore different and new intervention modalities that elicit
      significant social change. Moreover, these interventions should innovate the
      current treatments aimed at the social problems related to sexual work.

PMID- 9547834
TI  - Electrophysiology in the 19th century.

PMID- 9547833
TI  - Static or frictional electricity and the discovery of direct current.

PMID- 9547835
TI  - [Medical justice as a priority for Latin America].

PMID- 9547836
TI  - Four-step CPR--improving skill retention.
AB  - This study is an attempt to see if simplifying the teaching of basic life support
      leads to better skill acquisition and retention. Forty-eight lay volunteers
      received instruction in CPR; 24 were taught the standard 8-step sequence whereas
      24 were taught a simplified 4-step sequence. Tests of performance were carried
      out on a manikin before and after training. Those in the 4-step group were
      significantly better than those in the 8-step group at remembering the sequence
      of skills immediately after training (P = 0.04), 1 week later (P < 0.001) and at
      6 weeks (P < 0.001). Twenty-three out of the 24 volunteers in the 4-step group
      got the sequence completely correct each time they were tested, in contrast to
      only 2 out of the 24 in the 8-step group. There was no difference, however, in
      the quality of performance of the skills between the two groups. In addition, it
      was shown that use of the 4-step sequence should result in a useful reduction in
      the time taken before a rescuer calls for the emergency services and commences
      CPR. Whether such a radical change in teaching should be introduced is a matter
      for further discussion and research.

PMID- 9547838
TI  - Fatal outcome after polytrauma: multiple organ failure or cerebral damage?
AB  - To assess the relative importance of multiple organ failure (MOF) and cerebral
      damage on the mortality rate following trauma we analyzed retrospectively the
      records from 99 polytrauma patients admitted to a multidisciplinary European
      intensive care unit in a 2 year period. In all, 93% of the trauma was non
      penetrating and 73% was the result of road accidents. 28 patients died giving an
      overall mortality of 28.3%. The cause of death was cerebral lesions in 19
      patients, hemorrhagic shock in eight and multiple organ failure in one patient
      who had an injury severity score (ISS) of 13. Most deaths (78%) occurred within
      24 h of admission, 15 of these were due to extensive cerebral lesions and seven
      due to hemorrhagic shock. A total of six deaths occurred after 24 h, four due to
      extensive cerebral lesions, one due to hemorrhagic shock and one due to multiple
      organ failure. In our experience, cerebral damage was a more common cause of
      death than MOF following multiple non-penetrating trauma.

PMID- 9547837
TI  - Efficacy of cardiopulmonary resuscitation in pulseless paediatric trauma
      patients.
AB  - BACKGROUND: A study was designed to determine which paediatric trauma patients
      with no detectable vital signs are likely to benefit from cardiopulmonary
      resuscitation (CPR). METHODS: A 10-year retrospective study of all pulseless
      patients under 16 years of age with trauma in whom CPR was initiated in a
      prehospital or in-hospital setting in Southern Finland. RESULTS: Forty-one
      patients, 25 male and 16 female, were included in this study. The mean age was
      7.8 years (range 0.1-15.9 years). Twenty three patients had blunt injuries and
      three patients had penetrating injuries. The mean Injury Severity Score was 51
      (range 25-75). In 15 patients, the arrest was secondary to smoke inhalation,
      strangulation or electric shock. Resuscitation was initiated at the scene or en
      route in 28 patients and in 13 patients at the hospital. Five patients received
      open-chest CPR and 36 patients closed-chest CPR. Spontaneous circulation was
      restored in four patients with open-chest CPR and in six patients with closed
      chest CPR. Two patients had intact survival and one patient survived with
      moderate disability. The mechanism of traumatic cardiac arrest, initial cardiac
      rhythm or location of arrest did not seem to affect outcome of CPR. CONCLUSIONS:
      The overall survival rate of paediatric patients with cardiac arrest secondary to
      trauma is poor. Trauma patients in whom cardiac arrest is caused by respiratory
      arrest or by thoracoabdominal trauma in the hospital setting may have a chance of
      survival if a spontaneous circulation is rapidly restored with effective
      resuscitative measures.

PMID- 9547839
TI  - Tracheal intubation via the laryngeal mask airway: a viable alternative to direct
      laryngoscopy for nursing staff during cardiopulmonary resuscitation.
AB  - Eight nurses with no previous experience of advanced airway management were
      randomly assigned to be taught tracheal intubation either by direct laryngoscopy
      or via a laryngeal mask. Once competent in the technique using a manikin, they
      attempted a maximum of ten intubations on anaesthetised patients. They were then
      taught the alternative technique and the assessment repeated. Median times for
      practice were the same for both techniques. Intubation in under 30 s was
      successful via the laryngeal mask in 60% of patients (42/70) compared to 39%
      (27/70) when using a laryngoscope (P = 0.11). It appears that non-medical
      personnel can be successfully taught to intubate the trachea using the laryngeal
      mask as a conduit, for those circumstances where a cuffed tracheal tube is
      considered essential during resuscitation.

PMID- 9547840
TI  - Effectiveness of mask ventilation in a training mannikin. A comparison between
      the Oxylator EM100 and the bag-valve device.
AB  - The demands for an optimal ventilation apparatus are that it can be easily
      handled, achieves a sufficiently high ventilation volume, and minimizes gastric
      inflation. Our aim was therefore to carry out a study in a training mannikin to
      find out whether the Oxylator EM100, compared with the bag, obtains improved
      ventilation and a decrease in gastric inflation. In a randomized crossover study,
      72 subjects were selected (24 physicians, 44 nurses and 4 auxiliary nurses),
      chosen from the operating theatre, emergency department and intensive care unit
      of two hospitals. We used the Ambu-Bag Mark III with mask No. 4, the Oxylator
      EM100 with a pressure setting of 35 cm H2O run in the manual setting, the Ambu
      Man C mannikin as well as the Ambu-CPR computer program. The resuscitation cycles
      of the standard two-rescuer's adult procedure lasted 3 min each, with a 3-min
      pause between the crossover procedure. The participants could improve their
      ventilatory volume with the Oxylator EM100 by 635 ml (95% confidence interval 578
      692 ml) compared with the bag ventilation. The number of subjects who could
      attain a mean ventilatory volume of 800 ml or more increased from 15% to 98.6% (P
      < 0.001). Compared with the bag, the increase of adequate respirations (> or =
      800 ml) obtained by the Oxylator EM100 for the individual participants amounted
      to a median of 91% (P < 0.001). Moreover, conventional ventilation caused in 42%
      one or several instances of gastric inflation, whereas no such reactions occurred
      with the Oxylator EM100. The Oxylator EM100 showed significantly better results
      in the mannikin than the bag. Of most importance is a significant lowering of
      gastric inflation and less so a marked increase in ventilatory volume. Our trial
      procedure with a relatively high lung compliance and a high oesophageal sphincter
      opening simulated favorable conditions. Owing to a large in vivo variability of
      these magnitudes, a direct testing in real patients with circulatory arrest is
      indicated.

PMID- 9547841
TI  - Survival after cardiac arrest outside hospital in Sweden. Swedish Cardiac Arrest
      Registry.
AB  - The voluntary Swedish Cardiac Arrest Registry has collected and analyzed 14,065
      standardised reports on cardiac arrests up until May 1995. The reports have been
      collected from approximately half of Sweden's ambulance districts, which cover
      60% of the population. Resuscitation was attempted in 10,966 cases. The median
      age was 70 years. In 70.0% the arrest was witnessed, and in 43.3% the first
      recorded rhythm was VT/VF. Bystander-CPR was initiated in 32.3% of the cases.
      Most cardiac arrests took place at home (65.8%) and 67.1% were judged to be of
      cardiac origin. In 1692 cases (15.4%), the patient was admitted alive in hospital
      and 544 patients (5.0%) were alive after 1 month. Survival to 1 month in the
      subgroup which presented with VT/VF was 9.5%. We found no significant difference
      between survival in large cities and smaller communities. The survivors were
      analysed in relation to time to defibrillation and we found a strong correlation
      between a short time and increased survival.

PMID- 9547842
TI  - A rule for early outcome classification of out-of-hospital cardiac arrest
      patients presenting with ventricular fibrillation.
AB  - The aim of the study was to develop a scoring system for outcome classification
      at the start of prehospital first tier resuscitation for patients with cardiac
      arrest from ventricular fibrillation (VF). We studied a consecutive sample of 100
      out-of-hospital cardiac arrest patients, presenting with VF of presumed cardiac
      etiology on arrival of the first tier (in a two-tiered urban Emergency Medical
      Services system). The number of patients discharged was 29 ('survivors') and 71
      died ('non-survivors'). The electrocardiography (ECG) tracings recorded during
      resuscitation using a semi-automatic defibrillator were retrospectively analysed.
      For each patient, VF amplitude in mV (VF_a) and the number of base-line crossings
      per second (VF_blc) were calculated. Fisher's linear discriminant analysis was
      applied to discriminate between survivors and non-survivors using the variables
      VF_a, VF_blc and age. Patients were classed as potential survivors or non
      survivors using a survival index = 0.6*(VF_a) + 0.4*(VF_blc)-4.0. If for a given
      patient the survival index is < 0, he is classified in the non-survivor group, if
      the survival index is > 0, he is classified in the survivor group. Using this
      index 79% of the survivors and 70% of the non-survivors could be classified
      correctly. Adding age to the formula increased the correct classification of
      survivors to 86 and 73% for the non-survivors. The survival index provides a
      research tool for the discrimination between potential survivors and non
      survivors, which opens the possibility for the development of alternative
      treatment protocols in cardiac arrest.

PMID- 9547843
TI  - Neurological and circulatory outcomes of cardiopulmonary resuscitation in
      progress: influence of pre-arrest and arrest factors.
AB  - Possible correlations between the circulatory and neurological responses to
      cardiopulmonary resuscitation (CPR) and the influence of pre-arrest factors
      (demographic data, medical history and aetiology of circulatory arrest) and
      arrest factors (location of arrest, ECG configurations, and duration of
      resuscitation) on the course of circulatory and neurological recovery were
      investigated in 111 victims of circulatory arrest. At the start of resuscitation
      57 patients (Group I) had some brain function and 54 (Group II) had no brain
      function. Sixty nine patients (62%) had circulation restored but 54 (78%) were
      left with heart failure. Forty one patients (39%) survived the first day, 26
      (63%) with heart failure; only 34 (31%) were alive after 48 h, 17 (50%) with
      heart failure. Half of the patients surviving 24 or 48 h had awakened.
      Consciousness returned in 32 patients (29%) during the first 48 h, more
      frequently in Group I than in Group II. Patients in Group I had a higher
      incidence of in-hospital arrest and had their circulation restored more often
      than those in Group II. Survival and post-resuscitation heart failure was alike
      in the groups. The pre-arrest factors explored did not modify the circulatory or
      neurological outcome whereas initial ventricular fibrillation was significantly
      related to recovery of consciousness. The revivability of spontaneous circulation
      and of neurological functions was found thus mainly to be determined by global
      ischaemia sustained prior to and during CPR.

PMID- 9547844
TI  - Evaluating CPR performance in basic life support: the VIDRAP protocol.
AB  - This paper presents the second part of the validated Cardiff test for one rescuer
      basic life support skills, based on observation of video recording combined with
      the Recording Resusci Anne printout (VIDRAP). The authors believe that this is a
      robust evaluation tool which is capable of assessing the potential value to a
      casualty of a simulated resuscitation. The adoption of a widely accepted test
      methodology would facilitate comparison of research in different centres, which
      is not possible at present.

PMID- 9547845
TI  - Impact of a child first aid wall calendar on lay people's skills and knowledge of
      infant CPR.
AB  - The aim of the study was to evaluate whether mass-mailing of a 12-month wall
      calendar which focused on child and infant safety and first aid treatment had any
      educational effect on lay people. The calendar included algorithms for removal of
      a foreign body from the airways and infant and child CPR. The knowledge and
      skills in these procedures were tested in two groups using a previously validated
      check-list before and after the introduction of the calendar. One group received
      the calendar by mass mailing, free-of-charge. Six months after calendar
      distribution the mean result for 52 persons tested was 18% correct, not different
      from the 19% correct for 65 persons tested before calendar distribution. The
      other group received the calendar as part of an internal company campaign
      focusing on infant and child safety with a possibility for borrowing a baby
      manikin, but with no instruction involved. In this group the mean result improved
      significantly from 27% precalendar (n = 57) to 47% (n = 125) (P < 0.001) 1 week
      after calendar distribution with a significant reduction to 38% (n = 52) (P =
      0.004) 6 months later, still significantly better than precalendar (P = 0.004).
      Test persons younger than 50 years old scored better than those older than 50
      years (39 vs. 22%, P < 0.001), and the test persons scored better if they had
      been tested previously (44 vs. 35%, P = 0.04) or had practised with a baby
      manikin (45 vs. 35%, P = 0.02). Whether the test persons had children 0-8 years
      old or not, did not affect the results. In conclusion the calendar had no
      educational effect when distributed by mail, but a safety campaign which included
      distribution of the calendar and a possibility to borrow a manikin had a positive
      influence on the first aid skills and knowledge of lay people. Mass mailing of
      CPR or other first aid material free-of-charge does not seem to further the goal
      of increasing the rate and proficiency of bystander interventions to save lives.

PMID- 9547847
TI  - Severe ventilatory compromise due to gastric distention during pediatric
      cardiopulmonary resuscitation.
AB  - We describe a child in cardiac arrest with severe ventilatory compromise due to
      gastric distention. During cardiopulmonary resuscitation (CPR), positive pressure
      ventilation may lead to gastric insufflation because of decreased pulmonary
      compliance and decreased lower esophageal sphincter tone. Essentially, gas
      delivered will follow the path of least resistance, which may be to the stomach.
      In our patient, gastric distention precluded effective ventilation and gastric
      decompression relieved ventilatory compromise. The values and pitfalls of
      clinical evaluation and capnography are presented.

PMID- 9547846
TI  - Changes in brainstem auditory evoked response latency predict survival after CPR
      in a rat model of cardiac arrest and resuscitation.
AB  - Brainstem auditory evoked responses (BAER) are routinely used to monitor
      brainstem function in hospitalized comatose patients. We used a rat model of
      cardiac arrest and resuscitation to explore the possibility that the BAER,
      monitored during and immediately after cardiopulmonary resuscitation (CPR), could
      be used to determine whether the CPR was effective in restoring brainstem blood
      flow. Long-Evans rats were subjected to 7 min of cardiac arrest, induced by chest
      compression under Ketamine anesthesia sufficient to mechanically prevent the
      heart from pumping blood and were then resuscitated using a standard CPR
      protocol. During CPR, click stimuli were applied to one ear at 11/s and BAER
      averages recorded every 15 s. In three rats the BAER did not return after CPR;
      none of these rats respired spontaneously and all died. In 33 rats the BAER did
      return; within 15 min after the start of CPR BAER peak latencies decreased
      rapidly, increased again and then decreased. If the increase in the latency of
      the N2 peak was less than 0.3 ms, then the rat survived. If it was greater than
      0.35 ms the rat died. This signal was used as a cue for intervention in three
      rats; two survived. Thus, in this preparation, the BAER provided a useful measure
      of CPR effectiveness, in time to permit successful intervention.

PMID- 9547848
TI  - A reappraisal of mouth-to-mouth ventilation during bystander-initiated
      cardiopulmonary resuscitation.

PMID- 9547849
TI  - A reappraisal of mouth-to-mouth ventilation during initiated cardiopulmonary
      resuscitation.

PMID- 9547850
TI  - Immunosuppressive drugs in the treatment of inflammatory bowel disease.
AB  - Immunosuppressive (IS) drugs are an important option in the management of both
      forms of inflammatory bowel disease (IBD): Crohn's disease and ulcerative
      colitis. As the experience of using these agents in the treatment of IBD has
      increased and more data have become available on their efficacy, these drugs are
      being used more extensively. The principle drugs used in clinical practice at
      this time include: azathioprine (AZA) and its metabolite 6-mercaptopurine (6-MP),
      methotrexate, and cyclosporin A. AZA and 6-MP are generally considered the first
      line immunosuppressive agents. These drugs are effective and generally well
      tolerated by the majority of patients started on them, enabling many patients to
      avoid the predictable side effects of steroid therapy. Because of their extensive
      use, it is important that clinicians involved in the care of IBD patients are
      familiar with the IS drugs used to treat IBD, especially AZA and 6-MP.

PMID- 9547851
TI  - Medical management of perianal Crohn's disease.
AB  - Perianal disease is a frequent complication necessitating both medical and
      surgical management in Crohn's disease. Fissures, fistulae, or abscesses are
      found in approximately 36% of patients; occur more often in the ileocolonic and
      colonic disease; and may precede the onset of intestinal symptoms (Farmer et al,
      Gastroenterology 68:627-635, 1975; Rankin et al, Gastroenterology 77:914-920,
      1979; Gray et al, Gut 6:515-524, 1965; and Homan et al, Arch Surg 111:1333-1335,
      1976). To approach perianal manifestations, the physician must identify the
      anatomic location of the disease, treat the suppurative complications, and
      consider a long-term approach to palliation of chronic inflammatory sequelae.
      This article will review the medical management of perianal Crohn's disease and
      indications for surgery.

PMID- 9547852
TI  - Surgical options in the management of perianal Crohn's disease.
AB  - Perianal complications of Crohn's disease are common, and surgical management has
      been controversial. Over the last 10 years, improved outcomes have defined a more
      prominent role for operative interventions, especially with respect to management
      of focal perineal sepsis and fistulas. Liberal placement of drainage catheters
      and noncutting setons, advancement flap closure of perineal fistulas, and
      selective construction of diverting stomas have good results when combined with
      optimal medical therapy to induce remission of inflammation. Proctectomy, which
      is infrequently required, can often be postponed for several years when
      complementary surgical and medical treatments are provided.

PMID- 9547853
TI  - Nutritional issues and therapy in inflammatory bowel disease.
AB  - Nutritional issues in inflammatory bowel disease (IBD) often receive inadequate
      attention both in regard to therapy and nutritionally related complications of
      IBD. This article reviews much of the research that has evaluated the role of
      diet in the causation, primary treatment, and adjunctive therapy of both
      ulcerative colitis (UC) and Crohn's disease (CD). Benefits have been demonstrated
      in the use of elemental diets or polymeric diets in CD in both acute flare up or
      maintenance of IBD. A careful team approach can overcome problems in implementing
      nutritional therapy. Nutrition also has a critical benefit in postoperative CD
      and perioperative UC. Numerous easily corrected, nutritional abnormalities are
      often overlooked in patients with IBD, which may have significant consequences.
      Nutritional therapy may have a central place in the hierarchy of treatment in IBD
      and further research is critical in this area to better define the benefits of
      nutrition in IBD.

PMID- 9547854
TI  - The medical management of acute fulminant ulcerative colitis.

PMID- 9547855
TI  - Pharmacological and toxicological effects of chronic porcine growth hormone
      administration in dogs.
AB  - The purpose of this study was to evaluate the pharmacological and toxicological
      effects of exogenous GH administration in normal adult dogs. Because porcine GH
      (pGH) is structurally identical to canine GH, pGH was selected for a 14-wk study
      in dogs. Thirty-two dogs (< 2 yr) were randomized to 4 groups (4 dogs/sex/group);
      1 group was treated with the vehicle and 3 groups received pGH at 0.025, 0.1, or
      1.0 IU/kg/day subcutaneously. Daily clinical signs and weekly body weights were
      recorded. Hematology, serum biochemistry, urinalyses, electrocardiograms, and
      ophthalmoscopic examinations were done. Serum GH, insulin-like growth factor-1
      (IGF-1), insulin, thyroxine (T4), triiodothyronine (T3), and cortisol levels were
      determined. Necropsies were performed, organs weighed, and tissues were fixed and
      processed for light microscopic examination. Porcine GH caused increased body
      weight gain (p < or = 0.05) through the mid dose; the mean weight gains at study
      termination in mid- and high-dose groups were 2.8 kg and 4.7 kg, respectively,
      compared to 0.4 kg and 0.8 kg in control and low-dose groups, respectively. Dose
      related increased weights of liver, kidney, thyroid, pituitary gland, skeletal
      muscle, and adrenal gland were noted. In pGH-treated dogs, increased skin
      thickness seen grossly correlated histologically with increased dermal collagen.
      There was no gross or histomorphological evidence of edema. There were dose
      related increased serum IGF-1 levels (approximately 2-10-fold; p < or = 0.05)
      that correlated with the elevated serum GH levels in pGH-treated dogs. Also,
      increased serum insulin levels (p < or = 0.05) through the mid dose were seen
      throughout the study. In high-dose dogs, the insulin levels remained elevated
      over 24 hr postdose. The serum glucose levels in fasted dogs remained within the
      control range and there was no chronic hyperglycemia based on glycosylated
      hemoglobin levels. Renal glomerular changes, significant polyuria with decreased
      urine specific gravity, and increased serum insulin levels suggested that the
      dogs had early insulin-resistant diabetes. There was minimal or no biologically
      significant effect of pGH on serum T3, T4, and cortisol levels in dogs. Other
      serum biochemical changes in pGH-treated dogs included decreased urea nitrogen
      and creatinine, and increased potassium, cholesterol, and triglycerides.
      Significant increases in serum calcium and phosphorous levels and alkaline
      phosphatase activity (bone isozyme) correlated with the histological changes in
      bone. In pGH-treated dogs, there was a dose-related normochromic, normocytic,
      nonregenerative anemia. The changes described above, except for the anemia, are
      related to either anabolic or catabolic effects of high doses of GH. Based on
      this study, it is concluded that the dog is a good model in which to evaluate the
      safety of GH secretagogues as well as compounds with GH-like activity.

PMID- 9547856
TI  - Morphological changes in the pituitary gland of dogs chronically exposed to
      exogenous growth hormone.
AB  - Growth hormone (GH) synthesis and release from the pituitary is regulated by
      hypothalamic releasing hormone, insulin-like growth factor-1 (IGF-1), and
      somatostatin. However, the potential effects of pharmacological doses of
      exogenous GH on the pituitary are not well studied. To determine the potential
      chronic effects of exogenous GH on pituitary morphology in dogs, porcine GH (pGH)
      was administered subcutaneously to 3 groups of dogs (4 animals/sex/group) at
      doses of 0.025, 0.1, and 1.0 IU/kg/day for 14 wk. A group (4/sex) of dogs served
      as the vehicle control. The pituitaries from all dogs were weighed and fixed in
      appropriate fixatives for light and electron microscopic examination; in
      addition, cells of the pars distalis were quantitated by a point counting method
      following immunostaining to identify cells containing GH, prolactin (PRL), and
      adrenocorticotrophic (ACTH) hormones. Administration of pGH resulted in a
      statistically significant (p < or = 0.05) increased pituitary weight through the
      high dose. By light microscopy (LM), hypertrophy of pars distalis cells was
      evident in mid- and high-dose female dogs. The pituitaries of dogs given the
      lowest dose (0.025 IU/kg/day) of pGH were not remarkable based on weight and LM
      findings. In addition, transmission electron microscopic (TEM) examination of the
      pituitary gland of high-dose demonstrated, in both sexes, pituitary cells with
      variably dilated rough endoplasmic reticulum and decreased numbers of secretory
      granules; some of these cells reacted positively to GH immunostaining.
      Quantitative analysis of the pituitary gland of high-dose males and females
      showed an increase in the absolute volume of all cell populations studied: GH-,
      PRL-, and ACTH-positive cells. Based on the LM and TEM findings, the increased
      volume of the cell populations studied is likely related to cellular hypertrophy.
      The expected elevation in serum GH levels following repeated administration of
      pGH and an associated elevation in serum IGF-1 levels resulted in morphologic
      changes in the pituitary gland of dogs given high doses (> or = 0.1 IU/kg/day) of
      pGH; these observations differed from the reported findings in pituitaries of
      transgenic mice secreting large quantities of bovine GH.

PMID- 9547857
TI  - Effect of chronic growth hormone administration on skeletal muscle in dogs.
AB  - Administration of growth hormone (GH) results in increased body weight gain in
      dogs. Increased body weight gain is believed to be a result of the trophic effect
      of GH on the musculoskeletal system. However, edema is one of the side effects
      described in man following exogenous GH administration. Thus, the objective of
      this study was to determine if the expected increased weight gain in GH-treated
      dogs is a result of increased muscle mass. Porcine growth hormone (pGH),
      administered subcutaneously to beagle dogs at doses of 0.025, 0.1, and 1
      IU/kg/day for 14 wk, resulted in elevated serum GH and insulin-like growth factor
      1 (IGF-1) levels (see accompanying paper, Prahalada et al). This was associated
      with a significant increase in body weight gain and weights of the cranial
      tibialis muscle in both male and female dogs. The increased muscle mass likely
      contributed to the significant increase in body weight gain seen in both sexes.
      Quantitative analysis of skeletal muscle sections stained for ATPase activity
      showed increases in type I (slow twitch) and type II (fast twitch) myofiber sizes
      in mid- and high-dose males and in high-dose females. The ratio of type I and
      type II muscle fibers remained unchanged. Hypertrophic myofibers were enlarged
      but had a normal histologic and ultrastructural organization when observed by
      light and transmission electron microscopy. The results of this study have
      demonstrated that increased muscle mass in pGH-treated dogs is related to
      hypertrophy of muscle fibers and not due to edema. Exogenous GH administration
      has an anabolic effect on skeletal muscle in dogs.

PMID- 9547858
TI  - Growth hormone augmentation--a new era?

PMID- 9547859
TI  - Ocular irritation: microscopic changes occurring over time in the rat with
      surfactants of known irritancy.
AB  - The pathology of surfactant-induced ocular irritation, especially in the context
      of accidental human exposures and animal tests used to assess a surfactant's
      potential ocular irritation, is not well understood. The purpose of this study
      was to characterize the microscopic changes in rats at 3 hr and on days 1, 2, 3,
      4, 7, 14, and 35 following treatment with anionic, cationic, and nonionic
      surfactants of differing irritancy. The right eye of each rat was treated by
      placing 10 microliters of a surfactant directly on the cornea. Untreated left
      eyes served as the controls. At each time point, eyes and eyelids were
      macroscopically examined and collected for microscopic examination.
      Macroscopically, the differing levels of irritation were characterized by
      differences in incidence and magnitude of scores, reflecting involvement of the
      cornea, conjunctiva, and iris, as well as by the incidence of neovascularization
      and time to recovery. Microscopically, differences in the area and depth of
      injury paralleled the differences seen grossly and the relative irritancy of the
      various surfactants. All surfactants affected the corneal and conjunctival
      epithelium. All surfactants, except the slightly irritating anionic surfactant,
      caused corneal stromal changes, with this involvement being proportional to their
      overall level of irritation. Corneal endothelial cell effects principally
      occurred with only the severely irritating cationic surfactant. Over time,
      responses to surfactants of differing irritancy were qualitatively and
      quantitatively different, and these differences correlated with the extent of
      initial injury. Qualitative differences in response included presence of
      keratocyte regeneration, corneal neovascularization, and conjunctivalization of
      the corneal epithelium with all of the surfactants except the slight irritant.
      Quantitative differences in response occurred in the extent of epithelial
      regeneration, edema, and inflammation for surfactants of slight to severe
      irritancy, and with neovascularization, keratocyte regeneration, and
      conjunctivalization for surfactants of mild to severe irritancy. These results
      suggest that by defining initial area and depth of injury associated with an
      ocular irritant, it may be possible to predict the subsequent response and final
      outcome. Such an approach would be applicable to the development of
      mechanistically based in vitro assays.

PMID- 9547860
TI  - Ocular irritation: pathological changes occurring in the rat with surfactants of
      unknown irritancy.
AB  - We believe the development and validation of in vitro alternatives to eliminate
      the need to use animals in ocular irritation testing must be based on a thorough
      understanding of the mechanisms of ocular irritation. We have recently undertaken
      the task of developing such an understanding for a panel of surfactants. The
      purpose of this study was to expand our current panel of surfactants for which
      the microscopic changes occurring over time have been characterized. Macroscopic
      and microscopic findings regarding the ocular irritation of 6 surfactants of
      relatively unknown irritancy were compared to those of 6 surfactants of known
      irritancy. The right eye of each rat was treated by placing 10 microliters of a
      surfactant directly on the cornea. Untreated left eyes served as the controls. At
      3 hr and on days 1, 3, and 35, eyes and eyelids were collected for microscopic
      examination. Collectively, the macroscopic and microscopic findings revealed 3
      surfactants to be similar to the mildly irritating surfactants previously
      studied, and 3 surfactants to be similar to the moderately irritating surfactant
      previously studied. Information such as this will be important to develop
      mechanistically based in vitro alternatives to replace the use of animals for
      ocular irritation testing.

PMID- 9547861
TI  - Retinal degeneration in rats induced by CI-1010, a 2-nitroimidazole
      radiosensitizer.
AB  - The anti-cancer compound CI-1010, designated as (R)-alpha-([(2
      bromoethyl)amino]methyl)-2-nitro-1H-imidazole-1-ethanol monohydrobromide, has a
      proposed dual mechanism of action due to alkylating and radiosensitizing
      activities. To assess potential toxicity, adult Wistar rats were treated with a
      single intravenous injection (0, 50, 100, 150, 225, or 350 mg/kg) and necropsied
      at 4 or 29 days following treatment. In a repeated dose experiment, rats were
      injected daily (0, 10, 40, or 80 mg/kg; 5 doses/wk) for 3 wk and necropsied at
      the end of week 3 or 7. CI-1010 induced retinal degeneration by 4 days after a
      single injection of > or = 225 mg/kg or by 3 wk of repeated injections of > or =
      40 mg/kg. The locally extensive to diffuse retinal degeneration involved the
      photoreceptor and outer nuclear layer. The photoreceptor layer was vacuolated and
      compressed corresponding to ultrastructural evidence of inner segment swelling
      and outer segment fragmentation. The outer nuclear layer was thinned due to loss
      of nuclei and contained numerous pyknotic or karyorrhectic nuclei. These nuclear
      changes were morphologically consistent with apoptosis and many outer nuclear
      layer nuclei labeled with in situ TdT-mediated dUTP-digoxigenin nick end labeling
      (Apoptag). The retinal degeneration was nonreversible, evidenced by increased
      lesion severity and incidence after CI-1010 was withdrawn for either 25 or 28
      days.

PMID- 9547862
TI  - Receptor and nonreceptor-mediated organ-specific toxicity of di(2
      ethylhexyl)phthalate (DEHP) in peroxisome proliferator-activated receptor alpha
      null mice.
AB  - The peroxisome proliferator-activated receptor alpha (PPAR alpha) is the mediator
      of the biological effects of peroxisome proliferators through control of gene
      transcription. To determine if the toxic effects of di(2-ethylhexyl)phthalate
      (DEHP) are mediated by PPAR alpha, we examined its effect in PPAR alpha-null
      mice. Male Sv/129 mice, PPAR alpha-null (-/-) or wild-type (+/+) were fed ad
      libitum either a control diet or one containing 12,000 ppm DEHP for up to 24 wk.
      Significant body weight loss and high mortality was observed in (+/+) mice fed
      DEHP. By 16 wk, all DEHP-fed (+/+) mice had died of cystic renal tubular disease.
      In contrast, the (-/-) mice fed DEHP had no changes in body weight until later in
      the study nor increased mortality. Histologically, (+/+) mice fed DEHP had
      typical toxic lesions in liver, kidney, and testis while (-/-) mice fed DEHP had
      no toxic liver lesions but did show evidence of toxicity in kidney and testis
      after 4-8 wk of feeding, which progressed into moderate lesions by 24 wk.
      Analysis of hepatic and renal mRNAs showed a typical pleiotropic response in gene
      expression in the DEHP-fed (+/+) mice that was absent in the DEHP-fed (-/-) mice.
      These results provide evidence that PPAR alpha mediates the subacute-chronic
      toxicity of DEHP in liver, kidney, and testis. However, because (-/-) mice did
      develop toxic lesions in kidney and testis, DEHP can also act through PPAR alpha
      independent pathways in mediating renal and testicular toxicity.

PMID- 9547863
TI  - Immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine in paraffin-embedded
      sections of rat liver after carbon tetrachloride treatment.
AB  - To test the applicability of an anti-8-hydroxy-2'-deoxyguanosine (8-OH-dG)
      antibody for immunohistochemistry using paraffin-embedded sections, carbon
      tetrachloride (CCl4)-induced rat liver injury was evaluated. Male rats were given
      a single dose of CCl4 and killed at 6 hr, 12 hr, 1, 2, 3, and 7 days thereafter.
      Severe centrilobular necrosis was evident at 1 day. At 2 days, moderate
      mononuclear cell infiltration was present in centrilobular necrotic regions.
      Infiltrating mononuclear cells, surrounding sinusoidal endothelial cells and
      hepatocytes were stained with anti-8-OH-dG antibody at 2 and 3 days. Formation of
      8-OH-dG in DNA and 8-oxo-dGTPase mRNA expression were also increased at these
      time points, the amounts of malondialdehyde and 4-hydroxy-2-nonenal showed 2
      peaks at 6 hr and 3 days. The findings suggest that the main contributory factor
      in the massive hepatic necrosis was increased lipid peroxidation, rather than
      excessive formation of 8-OH-dG, and that the observed increase in the latter was
      largely due to infiltrating mononuclear cells. The agreement between biochemical
      data and the results for immunohistochemical analysis confirms that the anti-8-OH
      dG antibody is applicable for detection of cells targeted by free radicals in
      paraffin-embedded sections and also for investigation of the mechanisms of
      oxidative damage-related disease, including carcinogenesis.

PMID- 9547864
TI  - Effect of phenobarbital on hepatic gap junctional intercellular communication in
      rats.
AB  - The effects of in vivo exposure to phenobarbital (PB) on hepatic gap junctional
      intercellular communication (GJIC) and connexin protein expression in Sprague
      Dawley rats were examined by in vivolin vitro dye-transfer assay,
      immunohistochemical staining, and by Western blot analysis. PB (50 mg/kg) was
      administered orally once a day for up to 6 wk. The average size of the dye spread
      after injection of Lucifer Yellow decreased at week 1 and remained at the same
      level until week 6. The area and number of connexin 32 (Cx32) spots per
      hepatocyte in the central zone of liver lobules decreased from week 1 to week 6,
      but no change of Cx32 spots in the peripheral zone was observed. The average area
      and number of connexin 26 (Cx26) spots per hepatocytes showed no clear change
      through the experimental periods. The decreased level of Cx32 protein in plasma
      membranes was observed in the PB group. These results suggest that PB, a liver
      tumor-promoting agent, inhibits hepatic GJIC in vivo in rats and that aberrant
      Cx32 protein expression and/or localization may be responsible for this effect.

PMID- 9547865
TI  - Gap junction intercellular communication should be altered in mitosis.

PMID- 9547866
TI  - Systemic histopathology of rats treated with 6-sulfanilamidoindazole, a novel
      arthritogenic sulfonamide.
AB  - 6-Sulfanilamidoindazole (6SAI) is a sulfonamide that induces acute, self-limiting
      arthritis in rats, and 6SAI-induced arthritis is thought to be a model for
      testing anti-inflammatory agents. In this study, in order to clarify the location
      of arthritis and relationships between arthritis and other changes in this model,
      we have investigated the detailed pathologic changes in rats administered orally
      with 6SAI (125, 250, 500 mg/kg) daily for 4 wk in a time-course experiment.
      Moderate to severe arthritis was observed in rats of middle- and high-dose
      groups. Histologically, in the affected ankle, exudative synovitis and
      periarthritis were observed at 1 wk, granulation tissue formation with
      angiogenesis and periosteal new bone formation at 2 wk, and marked fibrosis of
      affected area at 4 wk, respectively. In addition to these changes, in
      periarticular and periosteal tissues of affected ankles, subendothelial
      insudation of small-sized arteries and medial fibrinoid degeneration of medium
      sized arteries were observed at 1 and 2 wk and intimal thickening and medial
      hypertrophy at 4 wk, respectively. No arterial changes were observed in the
      unaffected ankles. Similar arterial changes were often observed in the liver,
      thyroid glands, and lungs and rarely in various organs and tissues. Acute
      inflammation of serous tissues such as mesentery, mediastinum, and capsule of
      spleen or thymus were also present in 6SAI-treated groups, and it was sometimes
      accompanied by arteritis. In addition, in 6SAI-treated rats, follicular
      hyperplasia of thyroid glands and pituitary changes, which are thought to be
      related to depression of thyroid hormone production by 6SAI, were observed. These
      results show that 6SAI induces not only arthritis but also arteritis, serositis,
      and thyroid change, and it is necessary to take the interaction between these
      changes into consideration when anti-inflammatory agents are tested in this
      model.

PMID- 9547867
TI  - Effects of cholestyramine and diet on small intestinal histomorphometry in rats.
AB  - Reports on the effects of cholestyramine on small intestinal structure of rats
      have produced contradictory data about changes in mucosal histomorphometry,
      perhaps due to interacting effects of dietary composition. In order to identify
      effects of cholestyramine and diet on structure of the small intestines, 40 male
      rats were divided into 4 groups of 10 and fed 1 of each of the following diets
      for 1 month: standard diet, purified fiber-free diet, standard diet + 2%
      cholestyramine, or purified fiber-free diet + 2% cholestyramine. Serum
      concentrations of cholesterol and triglycerides were moderately increased in rats
      fed the purified fiber-free diet versus the standard diet. Neither total length
      nor weight of small intestine were affected by either diet or cholestyramine.
      Mucosal weight was affected by interactions between cholestyramine and diet,
      indicating that outcome depended upon modulating effects of both variables.
      Significant interactions were similarly detected among the variables of anatomic
      site, diet, and cholestyramine for many histomorphometric parameters of
      intestinal mucosa. Cholestyramine reduced total mucosal thickness in both jejunum
      and ileum and reduced villus height and villus:crypt ratio in the ileum.

PMID- 9547868
TI  - Brevetoxicosis in manatees (Trichechus manatus latirostris) from the 1996
      epizootic: gross, histologic, and immunohistochemical features.
AB  - In 1996, at least 149 manatees (Trichechus manatus latirostris) died in an
      unprecedented epizootic along the southwest coast of Florida. At about the same
      time, a bloom of the brevetoxin-producing dinoflagellates, Gymnodinium breve, was
      present in the same area. Grossly, severe nasopharyngeal, pulmonary, hepatic,
      renal, and cerebral congestion was present in all cases. Nasopharyngeal and
      pulmonary edema and hemorrhage were also seen. Consistent microscopic lesions
      consisted of catarrhal rhinitis, pulmonary hemorrhage and edema, multiorgan
      hemosiderosis, and nonsuppurative leptomeningitis. Immunohistochemical staining
      using a polyclonal primary antibody to brevetoxin (GAB) showed intense positive
      staining of lymphocytes and macrophages in the lung, liver, and secondary
      lymphoid tissues. Additionally, lymphocytes and macrophages associated with the
      inflammatory lesions of the nasal mucosa and meninges were also positive for
      brevetoxin. These findings implicate brevetoxicosis as a component of and the
      likely primary etiology for the epizootic. The data suggest that mortality
      resulting from brevetoxicosis may not necessarily be acute but may occur after
      chronic inhalation and/or ingestion. Immunohistochemical staining with
      interleukin-1-beta-converting enzyme showed positive staining with a cellular
      tropism similar to GAB. This suggests that brevetoxicosis may initiate apoptosis
      and/or the release of inflammatory mediators that culminate in fatal toxic shock.

PMID- 9547870
TI  - A communicating intestinal duplication in a Sprague-Dawley rat.
AB  - Duplications of the gastrointestinal tract are exceedingly rare in laboratory
      animals. We report a case of a communicating intestinal duplication in a 17-wk
      old Sprague-Dawley (SD) rat. The duplication was present in the mesenteric border
      of the ileum, and both proximal and distal ends were communicated with the lumen
      of ileum. Histologically, the duplicated portion had a thick muscle wall and a
      mucosa similar to that of the small intestine. This is the first reported case of
      intestinal duplication in an SD rat.

PMID- 9547869
TI  - Pathology of the oropharyngeal cavity in six strains of rats: predisposition of
      Fischer 344 rats for inflammatory and degenerative changes.
AB  - The sagittolongitudinal histopathological evaluation of the oropharyngeal cavity
      in 6 strains of rats revealed a clear predisposition of the Fischer 344 strain
      for degenerative and inflammatory lesions in this region. A degeneration and
      calcification predominantly of the laryngeal cartilage is evident in 72%,
      granulomas of the seromucinous glands in 38%, and an inflammation with bacterial
      colonies or plant material in the basal part of the laryngotracheal junction in
      26% of the Fischer 344 rats. The incidences of these types of lesions were
      negligible in the other rat strains evaluated. The comparison of control Fischer
      344 rats from 2 carcinogenicity studies (untreated group; gavaged group with
      water, pH 10; gavaged group with propylene glycol/methocel) showed an influence
      of the gavage technique with the solvent on the survival rate in the female
      Fischer 344 rats. The lower survival rate was accompanied by the occurrence of
      food impaction in the oropharyngeal cavity. This increased mortality in female
      Fischer 344 rats was also associated with a degeneration of the laryngeal
      cartilages, whereas the formation of granulomas and inflammation seemed to have
      no direct relationship to the mortality. The gavage technique with the applied
      solvent was an enhancing factor in the female Fischer 344 rats on mortality, on
      cartilage degeneration, but not on inflammatory changes. In contrast to the
      females, male Fischer 344 rats had a higher incidence of granulomas and
      inflammation, which, however, did not influence the survival rate. In conclusion,
      Fischer 344 rats, especially the female sex, exposed to chronic daily irritation
      by gavage, are predisposed to have a high mortality rate in chronic toxicologic
      tests. An explanation lies in the disposition of the Fischer 344 rat to a high
      incidence of cartilage degeneration, which presumably leads to a dysfunction of
      the larynx.

PMID- 9547871
TI  - Case report: pineocytoma in a male Fischer 344 rat.
AB  - An enlarged pineal gland was observed in a 112-wk-old male Fischer 344 rat from
      the low-dose treatment group in a 2-yr bioassay. Formalin-fixed, paraffin
      embedded sections of the gland were stained with hematoxylin and eosin along with
      the immunohistochemical biomarkers synaptophysin, placental alkaline phosphatase,
      glial fibrillary acidic protein, and vimentin. Based on its histomorphological
      features and on positive staining with synaptophysin, the lesion was diagnosed as
      a malignant pineal gland parenchymal cell tumor or pineocytoma of incidental
      origin.

PMID- 9547872
TI  - Spontaneous cystic keratinizing epithelioma in the lung of a Sprague-Dawley rat.
AB  - A spontaneous cystic keratinizing epithelioma in the lung of a 704-day-old female
      Hsd:Sprague-Dawley rat is described. The rat had a white subpleural discoloration
      on 1 diaphragmatic lobe at necropsy. Microscopically, a central keratin mass,
      surrounded by a multilayered squamous epithelium of varying thickness, was found.
      In the periphery of the tumor, epithelial nests projected multifocally into the
      adjacent alveolar spaces. Immunohistochemical labeling of nuclei by PCNA
      (proliferating cell nuclear antigen) revealed proliferative activity in 1 or 2
      peripheral cell layers in most locations. To the best of the authors' knowledge,
      this is the first report dealing with the morphological and immunohistochemical
      features of a spontaneous cystic keratinizing epithelioma in a rat.

PMID- 9547873
TI  - Mouse liver nodules induced by piperonyl butoxide, a mixed-function oxidase
      inducer.

PMID- 9547874
TI  - New indications for hyperbaric oxygen therapy and its complication.

PMID- 9547876
TI  - Hyperbaric oxygen therapy as a stimulator of osseointegration.

PMID- 9547875
TI  - Hyperbaric oxygen therapy in the management of osteoradionecrosis of the
      mandible.

PMID- 9547877
TI  - Hyperbaric oxygen therapy for necrotizing cervical infections.

PMID- 9547878
TI  - Effect of isobaric oxygen versus hyperbaric oxygen on the normal and noise
      damaged hypoxic and ischemic guinea pig inner ear.

PMID- 9547879
TI  - Effect of hyperbaric oxygen therapy in comparison to conventional or placebo
      therapy or no treatment in idiopathic sudden hearing loss, acoustic trauma, noise
      induced hearing loss and tinnitus. A literature survey.
AB  - With the published clinical data to hand on the therapeutic results of patients
      with idiopathic sudden hearing loss, acoustic trauma or noise-induced hearing
      loss, it may be confirmed that 65% of those polypragmatically treated patients
      demonstrated a hearing improvement of 19 +/- 4 dB. In 35% of the cases, no
      hearing improvement was detected independent of the drugs administered. This
      corresponds to the results obtained from placebo-treated patients who
      demonstrated a hearing improvement of 20 +/- 2 dB in 61% of cases and no hearing
      gain in 39% of cases (fig. 1). A different set of results was obtained from
      patients with a hearing loss who were treated either with prednisolone or
      placebo. The percentage of patients who achieved normal hearing again in the
      placebo-treated group amounted to 31% and 38% and in the verum-treated group 50%
      and 78%. It may be concluded that a placebo therapy is equally effective to that
      of all nonsteroidal drugs. Problems arise when comparing non-treated patients
      since information on spontaneous remission rates differs greatly in the
      references, i.e. between 25-68% for spontaneous full remissions and 47-89% for
      spontaneous partial remissions. From a statistical view, 35% and 39% of patients
      experienced no success with nonsteroidal drugs or placebo, respectively. These
      patients can still be helped with HBO therapy. 18 patients only underwent primary
      HBO therapy. In all other 50 studies evaluated here with a total of 4, 109
      patients suffering from idiopathic sudden hearing loss, acoustic trauma or noise
      induced hearing loss and/or tinnitus, HBO therapy was administered as a secondary
      therapy, i.e. following unsuccessful conventional therapy. If the onset of
      affliction was more than 2 weeks but no longer than 6 weeks, one half of the
      cases showed a marked hearing gain (in at least 3 frequencies of more than 20
      dB), one-third showed a moderate improvement (10-20 dB) and 13% showed no hearing
      improvement at all (fig. 2). 4% no longer experienced tinnitus, 81.3% observed an
      intensity decrease and 1.2% an intensity increase of their tinnitus condition.
      13.5% remained unchanged (fig. 2). If HBO therapy was administered at a later
      stage, but still within 3 months following onset of affliction, 13% showed a
      definite improvement in hearing, 25% a moderate improvement and 62% no
      improvement at all. 7% no longer suffered from tinnitus, 44% reported an
      intensity decrease, a similar percentage noticed no change and 5% a temporary
      deterioration of their tinnitus condition. If the onset of affliction was longer
      than 3 months up to several years, no hearing improvement can be expected in the
      majority of patients (fig. 3); however, one third of the cases reported an
      intensity decrease of tinnitus, 60-62% reported no change and 4-7% noticed a
      temporary intensity increase (fig. 4). In conclusion, it may be deduced that HBO
      therapy is recommended and warranted in those patients with idiopathic sudden
      deafness, acoustic trauma or noise-induced hearing loss within 3 months after
      onset of disorder.

PMID- 9547880
TI  - Hyperbaric oxygen therapy for sudden deafness.

PMID- 9547881
TI  - Hyperbaric oxygenation as a treatment for facial palsy.

PMID- 9547882
TI  - Otological complications of hyperbaric oxygen therapy.

PMID- 9547883
TI  - Drug therapy: the impact of managed care.

PMID- 9547884
TI  - The role of phosphodiesterase enzymes in allergy and asthma.

PMID- 9547885
TI  - Modulating protein kinase C signal transduction.

PMID- 9547886
TI  - Preventive role of renal kallikrein-kinin system in the early phase of
      hypertension and development of new antihypertensive drugs.

PMID- 9547887
TI  - The multienzyme PDE4 cyclic adenosine monophosphate-specific phosphodiesterase
      family: intracellular targeting, regulation, and selective inhibition by
      compounds exerting anti-inflammatory and antidepressant actions.

PMID- 9547888
TI  - Clinical pharmacology of systemic antifungal agents: a comprehensive review of
      agents in clinical use, current investigational compounds, and putative targets
      for antifungal drug development.

PMID- 9547889
TI  - Therapeutic monitoring of tacrolimus.

PMID- 9547890
TI  - Analytical aspects of antioxidants and free radical activity in clinical
      biochemistry.

PMID- 9547891
TI  - Renal tubular reabsorption of phosphate (TmP/GFR): indications and
      interpretation.

PMID- 9547892
TI  - Urine analysis in the diagnosis of mucopolysaccharide disorders.

PMID- 9547893
TI  - Simplified detection of a mutation causing familial hypercholesterolaemia
      throughout Britain: evidence for an origin in a common distant ancestor.
AB  - Familial hypercholesterolaemia (FH) is an inherited autosomal codominant disorder
      caused by many different mutations in the low-density lipoprotein receptor (LDLR)
      gene. The one described most frequently in patients with FH from England, arises
      from a G-->A transition at the first nucleotide of codon 80, resulting in the
      substitution of lysine for glutamic acid at residue 80 of the mature protein, FH
      E80K. We describe a simple method to detect this mutation in genomic DNA using
      the polymerase chain reaction (PCR). A 69 base pair (bp) fragment of exon 3 of
      the LDLR gene is amplified using a mutagenic upstream PCR primer. This
      substitutes a T for an A residue in the amplified product, 2 bp upstream from the
      mutant site, generating a restriction site for the endonuclease Taq I, in normal,
      but not in mutant DNA. Following digestion of amplified DNA with Taq I, normal
      but not mutant DNA is cut into two fragments of 29 and 40 bp, which are readily
      identified by polyacrylamide gel electrophoresis. Using this method, 410 patients
      with clinically diagnosed FH, attending lipid clinics in Edinburgh (72), Newport
      (158), Walsall (30) and Southampton (150), were screened for the mutation. Five
      individuals tested positive as heterozygotes, one from Edinburgh, three from
      Newport and one from Southampton. This finding was confirmed by DNA sequence
      analysis. We conclude that FH due to this mutation occurs in individuals
      throughout Great Britain and that it can be detected accurately using this simple
      technique. DNA from these and other individuals previously identified to be
      heterozygous for FH E80K, was then studied using PCR of highly informative
      microsatellite markers flanking the LDLR gene. Sixteen of 17 apparently unrelated
      individuals heterozygous for FH E80K also were heterozygous for an identical size
      (239 nucleotide) allele, of polymorphic microsatellite D19S394, located
      approximately 250 kb away from the LDLR gene. This supports the hypothesis that
      FH E80K in these 16 individuals arose from a single ancestor less than 1000 years
      ago.

PMID- 9547894
TI  - The assessment of platelet derived growth factor concentration in post myocardial
      infarction and stable angina patients.
AB  - Platelet derived growth factor (PDGF) has been implicated in the pathogenesis of
      atherosclerosis. PDGF is released by aggregating platelets and monocytes which
      gather around sites of arterial injury. In the study reported here the
      concentration of plasma PDGF was measured in post myocardial infarction (MI)
      patients (n = 28), angina patients (n = 25), and control subjects (n = 27).
      Venous blood samples were taken and the concentration of PDGF determined by an
      enzyme linked immunosorbent assay (ELISA). Plasma PDGF concentrations were
      significantly higher in the post MI group compared to both the control and angina
      groups (P < or = 0.05). The increase in PDGF concentration may be due to
      increased activation of platelets or monocytes since these two cells are major
      sources of plasma PDGF. High concentrations of PDGF in the circulation could
      further accelerate the progression of the disease.

PMID- 9547895
TI  - Serum sialic acid, a reputed cardiovascular risk factor, is elevated in South
      Asian men compared to European men.
AB  - Serum total sialic acid (TSA) has recently been reported as a cardiovascular risk
      factor, but whether there are racial differences is not known. One hundred and
      twenty-four healthy young subjects (62 women and 62 men) were studied. Their age
      was 20.7 [0.9] years and they were matched for body mass index (BMI). Sixty-eight
      were of South Asian origin (37 women and 31 men) and 56 (25 women and 31 men)
      were European. Mean (SD) serum TSA was significantly higher in the South Asian
      men than the age-matched European men (74.3 [12.3] mg/dL versus 68.2 [13.0]
      mg/dL, P = 0.0198). In addition, serum TSA was significantly higher in South
      Asian women compared with European men (71.6 [8.9] mg/dL versus 68.2 [13.0]
      mg/dL, P = 0.0352). Finally, serum TSA was significantly higher in European women
      compared with European men (76.0 [13.1] mg/dL versus 69.2 [13.0] mg/dL, P =
      0.008). We conclude that serum TSA may be worth measuring in different racial
      groups and also may be useful to assess individuals at risk of cardiovascular
      disease. Large prospective studies may help to explain why serum TSA is a reputed
      cardiovascular risk factor and shows racial differences.

PMID- 9547896
TI  - Preparation of urine samples for trace metal determination: a study with
      aluminium analysis by inductively coupled plasma optical emission spectrometry.
AB  - Urinary analysis of trace metals forms a significant role in clinical chemistry,
      but the optimal preparation and analysis of urine samples has not been
      investigated. Human urine is generally supersaturated with dissolved solids.
      Therefore, samples often precipitate following collection. X-ray microanalysis
      showed that this precipitate was predominantly rich in calcium and phosphorus but
      could include some trace metals from urine, potentially lowering their
      concentrations in solution. Hence, the precipitate must be fully redissolved for
      accurate analysis of trace metals in urine. Methods are emphasized for the best
      collection and preparation of urine samples for subsequent trace metal analysis;
      in this work inductively coupled plasma optical emission spectrometry (ICPOES)
      was used for the analysis of aluminium. For optimal accuracy, peak profiles were
      collected over 396.147 nm-396.157 nm. Urinary aluminium levels were investigated
      from 10 healthy volunteers and concentrations were obtained using either aqueous,
      pooled or individual urine-based standard curves. Since urine has a highly
      variable matrix, individual sample-based standards, which are unique to that
      particular sample, gave the most accurate results. However, where sample size is
      small or sample numbers are unfeasibly large, pooled sample-based standards give
      good approximations to within 15% and, with appropriate validation, other
      elements as internal standards could also be used for approximations. Aqueous
      standards should be avoided. Spike-recovery experiments confirmed these data
      since individual sample based standards showed optimal recovery [99.3 (4.4)%],
      while pooled sample-based standards were a close proxy [101.6 (9.2)%] but aqueous
      standards were inappropriate [137.4 (12.8)%]. Postprandial urinary aluminium
      levels of the 10 volunteers were [7.2 (3.7)micrograms/L] after analysis using
      individual sample-based standard curves.

PMID- 9547897
TI  - Oxidative stress of vanadium-mediated oxygen free radical generation stimulated
      by aluminium on human erythrocytes.
AB  - It has been suggested that aluminium stimulates vanadium-mediated superoxide
      radical generation. The oxidative stress of generated superoxide radicals on
      antioxidant enzyme activity, oxidation of NADH and NADPH, membrane lipid
      peroxidation and osmotic fragility in human red blood cells (RBC) was
      investigated. RBC were incubated with varying concentrations of vanadium and
      aluminium ions at 37 degrees C for 2 h. RBC incubated with vanadium ions showed
      significantly increased superoxide dismutase and catalase activities, and
      oxidized NADH and NADPH concentrations compared with control RBC preparations.
      Erythrocyte lipid peroxidation was assessed by measuring thiobarbituric acid
      reactivity. RBC incubated with elevated levels of vanadium showed significantly
      increased membrane lipid peroxidation when compared with control RBC; it
      increased further on addition of aluminium. A significant positive correlation
      was observed between the extent of vanadium induced membrane lipid peroxidation
      and the osmotic fragility of treated RBC. In the presence of vanadium, aluminium
      stimulates superoxide dismutase and catalase activities. NADH and NADPH oxidation
      and membrane lipid peroxidation, as well as increasing osmotic fragility of human
      erythrocytes. The stimulatory effect of aluminium was dependent on concentration.
      These results may have implications for the mechanism of toxicity of aluminium
      and vanadium in haemodialysis patients.

PMID- 9547898
TI  - Guidelines for the interpretation of analytical toxicology results and unit of
      measurement conversion factors.
AB  - A data compilation has been published on the World Wide Web [http://
      www.leeds.ac.uk/acb/annals] which aims to assist in the interpretation of
      analytical toxicology results in individual patients. 'Therapeutic' or 'normal'
      plasma/whole blood/urine concentrations, as well as the concentrations associated
      with serious toxicity (if known), for some 700 analytes of toxicological interest
      are given together with (when possible) relative atomic or formula masses, and
      mass/amount and amount/mass concentration conversion factors. This paper gives
      background and supplementary information which should be borne in mind when
      providing interpretation or using the Web table. Supplementary tables listing (i)
      common therapeutic drug monitoring assays and guidelines for interpretation of
      results, (ii) emergency toxicology analyses which may influence active treatment,
      (iii) blood carboxyhaemoglobin saturation and clinical features of toxicity, (iv)
      information important when interpreting the results of toxicology investigations,
      (v) factors which may affect interpretation of analytical toxicology results, and
      (vi) conversion factors for volatile compounds are included.

PMID- 9547899
TI  - A simple method for carbohydrate-deficient transferrin measurements in patients
      with alcohol abuse and hepato-gastrointestinal diseases.
AB  - Carbohydrate-deficient transferrin (CDT) is known to be increased in alcohol
      abuse. Several methods were developed for its measurement (e.g. isoelectric
      focusing with Western blotting or immunofixation, anion-exchange chromatography
      followed by immunoassays). We describe a greatly simplified isoelectric focusing
      technique which does not require immunofixation. CDT results obtained with this
      method were compared to other biological markers of alcohol abuse, i.e. mean
      corpuscular volume (MCV), aspartate aminotransferase (ASAT) and gamma-glutamyl
      transferase (GGT), in 55 patients distributed in three groups (i.e. healthy
      control subjects, control patients suffering from various hepato-gastrointestinal
      diseases and alcohol abusing patients). Sensitivity and specificity were 33-89%,
      61-57%, 89-49% and 83-100% for MCV, ASAT, GGT and CDT, respectively. We conclude
      that our method is highly suitable for routine clinical use.

PMID- 9547900
TI  - Glucose interference in the pancreolauryl test.
AB  - The influence of the glucose concentration in urines being assayed as part of a
      pancreolauryl test was investigated. Paired patient urines (n = 5) were assayed
      at 60 degrees and 70 degrees C, before and after spiking to 5% glucose. The
      influence of assay temperature alone was assessed using glucose-free paired
      patient urines (n = 10). Aqueous glucose solutions and spiked (5% glucose) normal
      random urines (n = 5) were assayed to assess the effect of glucose concentration
      alone. There was no difference in T/K ratios for glucose-free patient samples at
      60 degrees, 70 degrees and 80 degrees C. After spiking with glucose T/K ratios
      were significantly different when assayed at 70 degrees C, but not when assayed
      at 60 degrees C. Aqueous glucose solutions > or = 0.6% produced a pigment at
      temperatures > or = 65 degrees C which absorbed at the lambda max of fluorescein.
      Glucose was found to interfere in the pancreolauryl test. Caution should be
      exercised when interpreting results from glucosuric samples.

PMID- 9547901
TI  - Determination of free fatty acids in human bile by high-performance liquid
      chromatography.
AB  - We developed a high-performance liquid chromatography (HPLC) method for free
      fatty acids (FFAs) analysis in bile. In this method, FFAs were extracted from
      bile in a single step using an Isolute ODS cartridge, derivatized with 9
      anthryldiazomethane (ADAM). ADAM was chosen because of its high reactivity with
      carboxylic acid at room temperature. Then, HPLC was used for separating and
      quantifying FFAs. This method proved to be simple and time-saving. The mean
      recovery of FFA added to human gallbladder bile was 97.6%, and the detection
      limit was 100-250 pg. Using this method, we determined FFA concentrations in the
      gallbladder bile of 11 gallstone patients. The mean concentration of total FFA
      was 0.61 (SD = 0.41) mmol/L, and there was wide variation in the individual FFAs.

PMID- 9547902
TI  - A comparison of automated fructosamine and HbA1c methods for monitoring diabetes
      in pregnancy.
AB  - Two automated methods for measuring fructosamine (Test Plus and the original
      fructosamine assay) and glycated haemoglobin (Tina-quant immunoassay) were
      compared to determine which is the best index of blood glucose control during
      pregnancy. Thirteen women with type 1 diabetes were studied, with four-weekly
      measurements of HbA1c and fructosamine Test Plus using a Hitachi 911 analyser and
      fructosamine measured using an Olympus AU800 analyser. HbA1c correlated better (r
      = 0.573) with mean blood glucose (MBG) concentration than did fructosamine Test
      Plus (r = 0.347), even after correction for total protein concentration (r =
      0.463), while there was no significant correlation with the original fructosamine
      method (r = 0.201). HbA1c correlated better with fasting/pre-prandial MBG
      concentrations, whereas fructosamine Test Plus correlated better with post
      prandial MBG concentrations. Fructosamine Test Plus decreased with gestational
      age, and correlated with albumin and total protein concentrations, whereas HbA1c
      did not change with gestational age. Thus, HbA1c and fructosamine Test Plus were
      found to be useful in verifying home blood glucose measurements in diabetic
      pregnancy, with HbA1c being the best predictor of MBG concentration.

PMID- 9547903
TI  - Endothelin-1 production by human synoviocytes.
AB  - Immunoreactive (ir)-endothelin (ET)-1 concentrations in serum samples and
      synovial fluids from patients with rheumatoid arthritis were higher than
      concentrations in sera obtained from healthy volunteers. No significant
      difference in ir-ET-1 concentrations in synovial fluid was observed between
      rheumatoid arthritis patients and osteoarthritis patients. Cultured fluids of
      synovial cells collected from synovial tissues and leucocytes from synovial
      fluids of rheumatoid arthritis patients were studied to determine the origin of
      ir-ET-1 in synovial fluids. Ir-ET-1 was detected in the cultured fluids of
      synovial macrophage-like type A cells, but not in those of fibroblast-like type B
      cells from the synovial tissues or leucocytes from the synovial fluids.
      Longitudinal studies showed that the ir-ET-1 concentration in the cultured fluid
      reached a peak around 24 h after starting the culture. ET-1 secreted from
      macrophage-like synoviocytes may be involved in the pathogenesis of inflammatory
      arthritis.

PMID- 9547904
TI  - Isolation and properties of a novel phospholipase A from rat brain that
      hydrolyses fatty acids at sn-1 and sn-2 positions.
AB  - A Ca(2+)-independent phospholipase A that releases various fatty acids from sn-1
      and sn-2 positions was partially purified from rat brain soluble fraction. The
      enzyme showed an approximate molecular mass of 300 kDa on gel filtration column
      chromatography. Its enzymatic properties are distinct from those of well
      characterized phospholipase A2 enzymes; by using a series of synthetic
      phosphatidylcholines, the enzyme cleaved oleic, linoleic, and arachidonic acids
      like phospholipase A2, and released palmitic and stearic acids like phospholipase
      A1. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and
      phosphatidic acid were hydrolysed with almost equal efficiencies by this enzyme.
      These results indicate that the enzyme isolated is a novel Ca(2+)-independent
      intracellular phospholipase A that might be responsible for production of various
      fatty acids from membrane phospholipids.

PMID- 9547905
TI  - Butyrylcholinesterase genes in individuals with abnormal inhibition numbers and
      with trace activity: one common mutation and two novel silent genes.
AB  - A random population was screened for abnormal dibucaine and fluoride numbers (DN
      & FN) to find some common mutations in butyrylcholinesterase (BCHE) gene. Of 2375
      unrelated individuals, 10 were found to have low DN and FN and were selected for
      further studies. DNA analysis of these hypocholinesterasemics revealed that seven
      patients were heterozygous for missense mutation at codon 330 (TTA to ATA;
      BCHE*330I). The frequency of BCHE*330I mutation was calculated to be at least
      0.29% among the Japanese. On the other hand, two novel mutations were found in
      three families and two individuals including probands whose enzyme activity was
      very low (silent gene). Polymerase chain reaction and single stranded
      conformation polymorphism (PCR-SSCP) and restriction fragment length polymorphism
      (PCR-RFLP) were used for identification of the common and known mutation types
      such as BCHE*250P (ACT to CCT), BCHE*365R (GGA to CGA), and BCHE*539T (GCA to
      ACA; K-polymorphism), whereas PCR-SSCP was used in combination with direct DNA
      sequencing for new mutations like BCHE*446V (TTT to GTT) and BCHE*451X (GAA to
      TAA).

PMID- 9547906
TI  - Conversion of apolipoproteins A-1 and B reference limits obtained by a
      turbidimetric procedure to other methods.

PMID- 9547907
TI  - Falsely lowered FT4 and raised TSH concentrations in a patient with
      hyperthyroidism and human anti-mouse monoclonal antibodies.

PMID- 9547908
TI  - The effect of an unusual haemoglobin variant (beta 51Pro-->His) on haemoglobin
      A1c measurement.

PMID- 9547909
TI  - Osteocalcin following tibial shaft fracture.

PMID- 9547910
TI  - Diagnosing Cushing's syndrome.

PMID- 9547911
TI  - Haematocrit and the Boehringer advantage blood glucose meter.

PMID- 9547912
TI  - Air tube systems and safety.

PMID- 9547913
TI  - Lipoprotein (a) and ischaemic cerebrovascular disease.

PMID- 9547914
TI  - The Hemocue B glucose analyser and neonatal blood glucose monitoring.

PMID- 9547915
TI  - The Hemocue B glucose analyser and neonatal blood glucose monitoring.

PMID- 9547916
TI  - The Hemocue B glucose analyser and neonatal blood glucose monitoring.

PMID- 9547917
TI  - The Hemocue B glucose analyser and neonatal blood glucose monitoring.

PMID- 9547918
TI  - Serum antioxidant activity after myocardial infarction.

PMID- 9547919
TI  - Microalbuminuria in type 2 diabetic patients.

PMID- 9547920
TI  - Screening for prostatic carcinoma.

PMID- 9547921
TI  - Multiple auditory steady-state responses (MASTER): stimulus and recording
      parameters.
AB  - Steady-state responses evoked by simultaneously presented amplitude-modulated
      tones were measured by examining the spectral components in the recording that
      corresponded to the different modulation frequencies. When using modulation
      frequencies between 70 and 110 Hz and an intensity of 60 dB SPL, there were
      significant interactions between two stimuli when the carrier frequencies were
      closer than one half of an octave apart, with attenuation of the response to the
      lower carrier frequency. However, there were no significant decreases in response
      amplitude with four simultaneous stimuli provided the carrier frequencies
      differed by one octave or more. Higher intensities (70 dB SPL) resulted in
      greater interactions between the stimuli than when low intensities (35 dB SPL)
      were used. Modulation frequencies could be as closely spaced as 1.3 Hz without
      affecting the responses. Using broad-band noise as a carrier instead of a pure
      tone resulted in a significantly larger response when the stimuli were presented
      at the same sound pressure level. At modulation frequencies between 30 and 50 Hz,
      there were greater interactions between stimuli than at faster modulation
      frequencies. These results support the following recommendations for using
      multiple stimuli in evoked potential audiometry: (1) The multiple stimulus
      technique works well for steady state responses at frequencies between 70 and 110
      Hz. (2) Up to four stimuli can be simultaneously presented to an ear without
      significant loss in amplitude of the response, provided the carrier frequencies
      are separated by an octave and the intensities are 60 dB SPL or less. (3)
      Bandpass noise might serve as a better carrier signal than pure tones.

PMID- 9547922
TI  - Distortion-product otoacoustic emissions in middle-aged subjects with normal
      versus potentially presbyacusic high-frequency hearing loss.
AB  - Distortion-product otoacoustic emissions (DPOAEs) are still undergoing evaluation
      for clinical use. Although the effects of ageing on otoacoustic emissions have
      been studied quite extensively in the past, DPOAE response-growth or input-output
      (I-O) measures, which are well suited as an objective method for monitoring
      cochlear function at specific frequencies, have been less thoroughly examined.
      The aim of the present study was to assess the 2f1-f2 DPOAEs in a clinical
      setting in order to examine the response of 20 normally hearing middle-aged
      adults and to compare the results with those of 20 people of the same age with
      ears of sensorineural high-frequency hearing loss (HL). The experiment consisted
      of two stages. First, the DPOAE-gram was recorded in 1-4-octave steps at a
      stimulus level of 70 dB SPL over a frequency range of the f2 primary tone which
      extended from 1.001 to 6.299 kHz. Secondly, in order to elicit DPOAE I-O
      functions, the two primary stimuli were presented at equilevel intensities
      ranging from 20 to 71 dB SPL. The stimulus-level step size was 3 dB. The I-O
      functions were recorded at five separate DPOAE frequencies, with the f2 frequency
      most closely related to the clinical audiogram (f2 = 1.0, 1.5, 2.0, 4.0 and 6.0
      kHz). Two clearly separated portions in the form of the I-O function for normally
      hearing ears were found. The first portion, in response to primary levels of 60
      dB SPL and below, showed a plateau (saturating) behaviour. If primary levels
      exceeded 60 dB SPL, I-O functions became more linear. The attenuation of the
      saturation portion of the I-O function in ears with high-frequency HL across the
      frequency-test range is difficult to explain because elevated behavioural
      thresholds were observed only for frequencies > 1.5 kHz. Thus, the more linear I
      Os associated with the hearing-loss frequencies may indicate deficiencies in the
      active properties of outer hair cells (OHCs), whereas those for I-Os < 1.5 kHz,
      where hearing was normal, may indicate a beginning of damage to active OHC
      micromechanical processes prior to their clinical manifestation. DPOAE recordings
      from people with high-frequency HL, possibly age-related, supplement recordings
      of TEOAEs and give complementary information on degenerative changes in the outer
      hair-cells. DPOAE I-O functions may reveal discrete pathological alterations both
      in the active cochlear signal processing and in the passive mechanisms of the
      cochlea prior to their detection by clinical audiometric tests.

PMID- 9547923
TI  - Effects of click polarity on the auditory brainstem responses of older men.
AB  - This study was designed to evaluate the effects of stimulus polarity on the
      auditory brainstem responses (ABRs) in the older population. Nine men between the
      ages of 40 and 69 years participated in the study. Rarefaction and condensation
      clicks were delivered at 70 and 80 dB nHL to elicit the ABRs. The latencies were
      significantly earlier for rarefaction clicks for components II and V. The inter
      peak interval I-II was significantly shorter for rarefaction clicks than for
      condensation clicks. The amplitudes of the IV-V complex did not change with
      stimulus polarity at 80 dB nHL, but at 70 dB nHL larger amplitudes were observed
      with rarefaction clicks yielding a significant polarity-intensity interaction.
      The IV-V/I ratio elicited by rarefaction clicks was larger than that produced by
      condensation clicks at 80 dB nHL, but it was much larger for rarefaction clicks
      at 70 dB nHL resulting in a significant polarity-intensity interaction. The
      waveform morphology also changed with click polarity, with the most prominent
      effects apparent on components II and IV. A new hypothesis suggesting separate
      generators for ABRs recorded in response to the two click polarities is proposed.
      Use of both condensation and rarefaction clicks is recommended in recording ABRs
      for clinical use.

PMID- 9547924
TI  - Modulation detection by normal and hearing-impaired listeners.
AB  - In five normally hearing subjects and seven subjects with damaged cochleas,
      detection thresholds for sinusoidal frequency modulation (FM) and amplitude
      modulation (AM) were measured using 1 s stimuli with a 500 Hz carrier frequency
      (Fc) at a 'comfortable' loudness (given by subject-dependent SPLs and SLs). The
      modulation frequency (Fmod) was 2 Hz or 10 Hz. FM (but not AM) detection was
      poorer in the hearing-impaired group, especially when the hearing loss at Fc
      exceeded 50 dB. Fmod had a different effect on FM and AM detection. The
      corresponding interaction was essentially identical for the two groups of
      subjects. Previous studies strongly suggested that normal listeners use mainly
      neural phase-locking cues for the detection of FM when Fmod = 2 Hz, but mainly
      tonotopic cues when Fmod = 10 Hz. The present results suggest that cochlear
      damages reduce the usefulness of these two types of cues to an approximately
      equal degree.

PMID- 9547925
TI  - Neural networks as models of psychopathology.
AB  - Neural network modeling is situated between neurobiology, cognitive science, and
      neuropsychology. The structural and functional resemblance with biological
      computation has made artificial neural networks (ANN) useful for exploring the
      relationship between neurobiology and computational performance, i.e., cognition
      and behavior. This review provides an introduction to the theory of ANN and how
      they have linked theories from neurobiology and psychopathology in schizophrenia,
      affective disorders, and dementia.

PMID- 9547926
TI  - Hippocampal neuronal dysfunction in schizophrenia as measured by proton magnetic
      resonance spectroscopy.
AB  - BACKGROUND: Previous neuropathological and neuroimaging studies have documented
      neuronal loss in the hippocampal region in schizophrenia. N-acetylaspartate (NAA)
      is a neuronal/axonal marker that may be utilized to assess neuronal loss or
      dysfunction by proton magnetic resonance spectroscopy (1H MRS). This study
      measured NAA, choline, and creatine in the hippocampal region of patients with
      schizophrenia using in vivo proton magnetic resonance spectroscopic imaging (1H
      MRSI). METHODS: 1H MRSI was performed on the right and left hippocampal regions
      in 30 chronic schizophrenic patients and 18 control subjects. Concentration
      estimates of NAA, creatine, and choline were determined. RESULTS: Relative to the
      control group, the patients with schizophrenia demonstrated significantly lower
      NAA in both the right and left hippocampal regions. No group differences in
      choline were noted; however, there was a trend for creatine to be higher on the
      left than the right hippocampus in the schizophrenic group. There was also no
      association between NAA and duration of illness or medication dosage.
      CONCLUSIONS: This preliminary study provides support for neuronal dysfunction
      and/or decreased neuronal density in the hippocampal region. The absence of
      choline signal elevation does not support accelerated turnover of membrane
      phospholipids, which might be expected if there were ongoing neuronal atrophy or
      neuronal necrosis.

PMID- 9547927
TI  - Psychobiological heterogeneity of familial and sporadic schizophrenia.
AB  - BACKGROUND: Although schizophrenia is presumed to be heterogeneous, there has
      been limited success distinguishing familial from sporadic cases. We used
      psychobiological measures to examine heterogeneity, as they may be closer to
      neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and
      dichotic listening (DL) tests to tones and words were used to assess hemispheric
      laterality asymmetry. METHODS: Forty-six research unit patients participated in
      assessments of family history (FH) and physiological measures. FH was categorized
      by three exclusive groups: FH-1 patients had a chronic schizophrenia-related
      psychosis in a first-degree relative, FH-2 had it in second-degree relative, and
      FH-3 had no family member with a reoccurrence. RESULTS: Analysis of variance
      showed a significant group difference for SPEM and DL tones. SPEM was
      significantly worse in all three schizophrenia groups than for the normal
      comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3)
      had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best
      quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric
      lateralization for tones, whereas familials did not, and FH-2 again had
      intermediate values. The lateralization quotient for DL words did not
      significantly differ among the groups. CONCLUSIONS: SPEM was affected most in
      sporadic, not familial schizophrenia, whereas dichotic listening was most
      affected in familial schizophrenia. This double dissociation supports the utility
      of the familial/sporadic distinction and suggests that etiological factors in
      different forms of schizophrenia may impact principally on distinct
      neurobiological substrates, despite similar patient phenomenology.

PMID- 9547928
TI  - Olfactory deficits in patients with schizophrenia and severe polydipsia.
AB  - BACKGROUND: The present study was designed to assess olfactory function in
      severely polydipsic/hyponatremic patients with schizophrenia who also had
      intermittent water intoxication. METHODS: The University of Pennsylvania Smell
      Identification Test and an olfactory acuity battery were administered to three
      groups of male subjects: 9 patients with schizophrenia and severe
      polydipsia/hyponatremia, 9 control nonpolydipsic/normonatremic patients with
      schizophrenia, and 9 normal controls. RESULTS: Male patients with severe
      polydipsia/hyponatremia and intermittent water intoxication had marked olfactory
      acuity and identification deficits when compared to the patient control group of
      similar age and age at illness onset, and to normal controls. CONCLUSIONS: The
      finding of deficient acuity (detection threshold) in the polydipsic/hyponatremic
      group but not the nonpolydipsic, normonatremic group suggests that for this
      subgroup, abnormalities of olfactory sensory function may occur in a pattern
      previously reported for other brain disorders such as Alzheimer's disease.

PMID- 9547929
TI  - An analysis of the brain's transfer properties in schizophrenia: amplitude
      frequency characteristics and evoked potentials during sleep.
AB  - BACKGROUND: Classical analysis of spontaneous sleep electroencephalogram (EEG) in
      schizophrenia commonly reveals alterations of sleep continuity, number of
      awakenings, slow-wave sleep (SWS), and REM sleep compared to healthy controls;
      however, conventional analysis cannot help understand dynamic differences of the
      sleep EEG during different sleep stages. METHODS: We measured late components of
      auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) during
      different sleep stages of 11 schizophrenic inpatients and in a sex- and age
      matched control group from scalp positions FZ, CZ, and PZ. According to linear
      system theory, we then computed the amplitude-frequency characteristic (AFC) from
      averaged AEPs and VEPs in different sleep stages. These AFCs describe the input
      output relation of the system under study, leading to a characterization of the
      transfer properties of the schizophrenic brain during sleep. RESULTS: Significant
      differences could be found for the transfer properties during stage II and SWS
      between schizophrenics and controls. During REM a marked enhancement of theta
      resonance was seen in schizophrenics. CONCLUSIONS: The results of the present
      study point to highly different central nervous system transfer properties in
      schizophrenics and controls. Compared to previous investigations in depression,
      the results provide additional information for distinguishing schizophrenia and
      depression in EEG studies.

PMID- 9547931
TI  - Clozapine and body mass change.
AB  - BACKGROUND: Patients treated with clozapine have been reported to gain weight. We
      hypothesized that patients would also experience an increase in body mass, which
      can be more directly related to cardiovascular morbidity. METHODS: Forty-two
      patients who had been treated with clozapine for at least 1 year were weighed and
      measured, and waist-hip ratios (WHR) and body mass index (BMI), measured as
      kg/m2, were calculated. Patients were also asked about a series of factors
      potentially related to change in body mass. RESULTS: Female patients gained both
      weight and body mass. Their WHR after 37 months of clozapine therapy was .83,
      with a significant increase in BMI from 23.2 to 29.1 kg/m2 (p = .001). Male
      subjects also gained weight and body mass. Their WHR after 39 months of clozapine
      therapy was .93, with a significant increase in BMI from 26.4 to 29.7 kg/m2 (p <
      .001). Stepwise multiple-regression analysis showed that factors related to final
      body mass were initial body mass, dose of clozapine, and decrease in smoking.
      Baseline BMI contributed most to the final BMI, but the addition of dose and
      decrease in smoking made significant contributions to the model. CONCLUSIONS:
      Both female and male patients treated with clozapine gain body mass. This may
      place them at greater risk for cardiovascular morbidity.

PMID- 9547930
TI  - A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by
      amphetamine and the development of haloperidol-induced supersensitivity to
      amphetamine.
AB  - BACKGROUND: A novel gastric pentadecapeptide, BPC 157, has been shown to
      attenuate different lesions (i.e., gastrointestinal tract, liver, pancreas,
      somatosensory neurons). This suggests an interaction with the dopamine system.
      When used alone, BPC 157 does not affect gross behavior or induce stereotypy.
      METHODS: We first investigated the effect of pentadecapeptide BPC 157 on
      stereotypy and acoustic startle response in rats, given as either a prophylactic
      (10 micrograms/kg i.p.) or therapeutic (10 ng/kg i.p.) regimen, with the dopamine
      indirect agonist amphetamine (10 mg/kg i.p.). RESULTS: There was a marked
      attenuation of stereotypic behavior and acoustic startle response. When the
      medication was given at the time of maximum amphetamine-induced excitability,
      there was a reversal of this behavior. A further focus was on the effect of this
      pentadecapeptide on increased climbing behavior in mice pretreated with the
      dopamine antagonist haloperidol (5.0 mg/kg i.p.), and subsequently treated with
      amphetamine (20 mg/kg i.p. challenge 1, 2, 4, and 10 days after haloperidol
      pretreatment). This protocol is usually used for the study of behavioral
      supersensitivity to the amphetamine stimulating effect. CONCLUSIONS: An almost
      complete reversal was noted when pentadecapeptide was coadministered with
      haloperidol. Together, these data provide compelling evidence for the interaction
      of pentadecapeptide BPC 157 with the dopamine system.

PMID- 9547932
TI  - Cortisol and response to dexamethasone as predictors of withdrawal distress and
      abstinence success in smokers.
AB  - BACKGROUND: Glucocorticoids have been linked to self-administration of a wide
      range of drugs in animals and are increased endogenously by chronic nicotine
      intake. Corticosteroids have also been shown to regulate nicotine receptor
      sensitivity and to be involved in behavioral sensitization to nicotine. METHODS:
      Cortisol levels and cortisol suppression in response to dexamethasone were
      measured in a sample of smokers participating in a smoking cessation treatment
      trial. RESULTS: Cortisol levels dropped significantly during the early quitting
      process (2 weeks post-quit) and returned to a level below baseline 1 month post
      quit. The magnitude of the initial drop in cortisol was strongly related to post
      quit distress and marginally predictive of abstinence. Neither baseline nor post
      quit changes in percent cortisol suppression after dexamethasone were related to
      abstinence success or withdrawal distress. CONCLUSIONS: Withdrawal from cigarette
      smoking is marked by a reduction in cortisol levels that appears to be related to
      the degree of distress experienced during the early quitting period. Further work
      is needed to determine whether withdrawal-related cortisol changes or distress
      are predictive of abstinence success.

PMID- 9547933
TI  - Salivary cortisol and cardiovascular activity during stress in oppositional
      defiant disorder boys and normal controls.
AB  - BACKGROUND: Arousal-regulating mechanisms are important in explaining individual
      differences in antisocial behavior. METHODS: Alterations in salivary cortisol
      concentration and cardiovascular activity were studied in 21 boys with
      oppositional defiant disorder (ODD) and 31 normal controls (NC) during a 2-hour
      stressful procedure involving frustration and provocation. RESULTS: Baseline
      levels of heart rate (HR) were significantly lower in the ODD group, but their HR
      levels were higher during provocation and frustration. Cortisol levels in the ODD
      group were overall lower than those of the NC group, and the effect of stress
      seemed to be minimal and similar for both groups; however, individual differences
      were large. Since anxiety plays an important mediating role in cortisol response,
      subjects were divided into one of four groups based on the intensity of their
      externalizing behavior and anxiousness. Cortisol increase due to stress exposure
      was strongest in highly externalizing and highly anxious subjects; cortisol
      decrease was strongest in those subjects who were high in externalizing behavior
      and low in anxiousness. CONCLUSIONS: The results of the study support an
      important role for hypothalamic-pituitary-adrenal axis sympathetic autonomic
      functioning in persistent antisocial behavior in young boys.

PMID- 9547934
TI  - Chronic disulfiram treatment effects on intranasal cocaine administration:
      initial results.
AB  - BACKGROUND: Simultaneous abuse of cocaine and alcohol is common. Alcohol
      decreases negative stimulant effects and potentiates "high." Disulfiram
      (Antabuse) is being studied in outpatient trials as a cocaine pharmacotherapy
      with the rationale that inability to modulate cocaine effects with alcohol may
      decrease cocaine use. METHODS: We examined the interaction of disulfiram and
      cocaine in a randomized, double-blind, placebo-controlled study where subjects
      were chronically treated with disulfiram and then participated in intranasal
      cocaine administration studies. RESULTS: Disulfiram 250 mg/day treatment
      significantly increased plasma cocaine concentrations (p = .013), heart rate
      (cocaine 1 mg/kg, p = .046), and systolic (cocaine 2 mg/kg p = .003) and
      diastolic (cocaine 2 mg/kg, p = .022) blood pressure. "High" and "nervous"
      ratings were nonsignificantly increased. CONCLUSIONS: The combination of "high"
      with increased anxiety in the context of inability to lessen negative effects
      with alcohol may be an effective treatment in selected patients. The significant
      pharmacokinetic interaction must be considered in the decision regarding use of
      disulfiram.

PMID- 9547935
TI  - Heart rate variability as an index of cue reactivity in alcoholics.
AB  - BACKGROUND: Autonomic responses follow exposure to conditioned stimuli such as
      contextual factors associated with alcohol ingestion. Heart rate variability is
      under autonomic control and may be a measure of such response. METHODS: Twenty
      alcoholics and 23 matched social drinkers (all male) were exposed to a neutral
      cue and then an alcohol cue in identical settings, during which the
      electrocardiogram of these subjects was recorded. Time and frequency domain
      parameters of heart rate variability (HRV) were computed by a blind rater.
      RESULTS: Coefficient of variation of R-R intervals and absolute powers of HRV
      spectrum (in frequency bands 0.05-0.15 Hz and 0.01-0.05 Hz) following alcohol cue
      were significantly higher in alcoholics than social drinkers. The mean heart rate
      (MHR) failed to reflect this difference. CONCLUSIONS: HRV paradigm appears more
      sensitive than MHR to measure cue reactivity.

PMID- 9547936
TI  - Substituted pyrido[3,2-b]oxazin-3(4H)-ones: synthesis and evaluation of
      antinociceptive activity.
AB  - A new series of N-substituted pyrido[3,2-b]oxazinones has been synthesized,
      pharmacologically evaluated, and compared with acetyl salicylic acid. The
      compound with the maximal combination of safety and analgesic efficacy was 4-?3
      [4-(4-fluorophenyl-1-piperazinyl)propyl]?-2H-pyrido[3,2-b]-1, 4-oxazin-3(4H)-one
      (6c) with ED50 values of 12.5 mg/kg po (mouse: phenylquinone writhing test) and
      27.8 mg/kg po (rat: acetic acid writhing test), respectively. Compound 6c proved
      to be more active than aspirin with a safety index of 5.1.

PMID- 9547938
TI  - Probing the conformation of bilirubins with monopropionic analogs: a biological,
      spectroscopic, and molecular modeling study.
AB  - The in vivo metabolism of a bilirubin analog substituted with a propionic acid
      chain in C8 (5) showed that it is excreted in bile conjugated with glucuronic
      acid, while a positional isomer substituted with a propionate in C7 (6) is
      excreted in bile without conjugation. A conformational analysis employing an
      optimized Monte Carlo method and a mixed Monte Carlo/stochastic dynamics reveals
      that isomer 5 adopts a 'ridge tile' conformation, stabilized by the presence of
      three intramolecular hydrogen bonds. On the contrary, isomer 6 exhibits a more
      closed structure, where impairment in the formation of at least one of the
      hydrogen bonds occurs. These theoretical predictions agree well with 1H NMR, UV
      vis, and TLC data.

PMID- 9547937
TI  - 1-Methyl-3-pyrrolines and 2-methylisoindolines: new classes of cyclic tertiary
      amine monoamine oxidase B substrates.
AB  - Both 1-methyl-3-pyrrolines and 2-methylisoindolines are substrates for MAO-B with
      Vmax/Km values ranging from 200 to 2000 min-1 mM-1 at 37 degrees C. These
      compounds represent new classes of cyclic tertiary amine substrates for this
      flavoenzyme. The only other known cyclic amines that are MAO-B substrates are 1,4
      disubstituted 1,2,3,6-tetrahydropyridinyl derivatives. The presence of an allylic
      (benzylic) amino functionality in all of these compounds may be linked to their
      substrate properties since related piperidinyl and pyrrolidinyl analogs are
      stable in the presence of MAO-B. This paper discusses energetic and geometric
      features of these compounds in relationship to their substrate properties and in
      anticipation of their utility to probe the active site of this flavoenzyme.

PMID- 9547939
TI  - Quantitative structure-activity relationships on 5-substituted terbenzimidazoles
      as topoisomerase I poisons and antitumor agents.
AB  - Several 5-substituted terbenzimidazoles were synthesized and evaluated as
      mammalian topoisomerase I poisons and for cytotoxicity against a human
      lymphoblastoma cell line, RPMI-8402. No correlation was observed between
      topoisomerase I poisoning activity and the Hansch pi value or the sigma meta and
      sigma para values associated with each substituent. These data suggest that
      electronic effects and relative lipophilicity of substituents at the 5-position
      of these terbenzimidazoles do not have a significant effect upon intrinsic
      topoisomerase I poisoning activity. There was, however, a good correlation
      between the relative pi values for the various substituents evaluated and
      cytotoxic activity. Experimentally determined log P values did not correlate well
      with either cytotoxicity or pi values. Capacity factors (log k') as determined by
      high pressure liquid chromatography did correlate well with the pi values of
      varied substituents and cytotoxicity. These data indicate that the relative
      lipophilic activity of substituents at the 5-position of these terbenzimidazoles
      can strongly influence relative cytotoxic activity.

PMID- 9547940
TI  - Synthesis and biological evaluation of 2,6-di-tert-butylphenol hydrazones as 5
      lipoxygenase inhibitors.

PMID- 9547941
TI  - Potential inhibitors of plasmodial heme oxygenase; an innovative approach for
      combating chloroquine resistant malaria.
AB  - Syntheses of imidazo-pyridines and substituted prolines and their effect on heme
      oxygenase activity of Plasmodium yoelii and corresponding infected host have been
      studied. Six compounds in vitro and one in vivo showed selective inhibition of
      parasite enzyme which may be further exploited in the development of resistant
      reversal agents.

PMID- 9547942
TI  - Two related neurokinin-1 receptor antagonists have overlapping but different
      binding sites.
AB  - The neuropeptide substance P binds to the G protein-coupled neurokinin-1 (NK-1)
      receptor and elicits cellular responses thought to be involved in pain,
      neurogenic inflammation, vasodilatation, and plasma exudation. Several small
      molecule nonpeptide antagonists of the substance P/NK-1 receptor interaction have
      been developed. Mutational analysis of the receptor protein sequence has led to
      the conclusion that the binding site for these nonpeptide antagonists lies within
      the bundle created by transmembrane domains IV-VII of the receptor. This current
      investigation employs site directed mutagenesis of the NK-1 receptor to compare
      the binding site of CP-96,345 with that of a related compound CP-99,994. The data
      demonstrate that while both compounds appear to bind within the transmembrane
      domain bundle, the contribution of individual amino acid residues to the binding
      of each compound differs.

PMID- 9547943
TI  - Aminobicyclo[2.2.1.]heptane dicarboxylic acids (ABHD), rigid analogs of ACPD and
      glutamic acid: synthesis and pharmacological activity on metabotropic receptors
      mGluR1 and mGluR2.
AB  - Isomeric norbornane-derived rigid analogs mimicking different potential
      conformations of ACPD (1-aminocyclopentane-1,3-dicarboxylic acid) and glutamic
      acid have been synthesized, via the hydantoin route, to be used as conformational
      probes for bioactive conformations at the glutamatergic receptors of the central
      nervous system. Activities on metabotropic receptors mGluR1 and mGluR2 are
      reported and discussed.

PMID- 9547944
TI  - Transferred nuclear Overhauser effect study of macrolide-ribosome interactions:
      correlation between antibiotic activities and bound conformations.
AB  - The study of macrolide-ribosome interactions has been investigated using two
      dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY). A new
      medically important macrolide antibiotic, roxithromycin, with the replacement of
      the 9-keto group in erythromycin by a 9-oxime chain, was studied in the complex
      state with the bacterial ribosome. Analysis of transferred nuclear Overhauser
      effect (TRNOE) experiment resulted in a set of constraints for all protons pairs.
      These constraints were used in structure determination procedures based on
      molecular modelling to obtain a bound structure compatible with the experimental
      NMR data. The results compared with the conformational analysis of the substrate
      in solution indicate that only one specific conformation is preferred in the
      bound state while in the free state the sugar ring moities were relatively
      disordered. The bioactive macrolide antibiotics studied roxithromycin and
      erythromycin which displayed a strong NMR response, are metabolized in RU39001
      and erythralosamine respectively which do not retain antimicrobial activity. The
      inactive major metabolites were used to define if TRNOEs observation may be
      characteristic of a biological activity. These control experiments gave
      essentially blank TRNOESY spectra. This study shows that Mg2+ does not play a
      direct role for the low affinity binding site studied by TRNOE what is in
      agreement with an hypothesis of two distinct binding levels, with a low affinity
      binding level necessary for the tight binding one.

PMID- 9547945
TI  - Conformational studies on resiniferatoxin (RTX), an ultrapotent vanilloid
      agonist.
AB  - In polar solution, NOE studies show a pronounced clustering of the aromatic
      moieties (9,13,14-phenylacetate orthoester and 20-homovanillate) of the
      ultrapotent vanilloid agonist resiniferatoxin (RTX). This clustering is absent in
      nonpolar solution. Low energy clustered structures from molecular dynamics
      simulations account for the observed NOEs. These results suggest that the
      phenylorthoacetate moiety can assist the attainment of specific alignments
      between the terpenoid core and the vanillyl moiety, possibly preorganizing them
      for ideal receptor binding.

PMID- 9547947
TI  - A novel type of structurally simple nonpeptide inhibitors for alpha-chymotrypsin.
      Induced-fit binding of methyl 2-allyl-3-benzenepropanoate to the S2 subsite
      pocket.
AB  - Unexpectedly, methyl and benzyl esters of 2-allyl-3-benzenepropanoic acid were
      found to be not substrates but potent competitive inhibitors for alpha
      chymotrypsin. The inhibitory property of the structurally simple nonpeptidic
      compounds is ascribed to their high binding affinity to the enzyme at the S2
      rather than S1 subsite pocket. These inhibitors exist in a flexible form in
      solution, but as they bind to the enzyme bulky contrained conformers present in a
      minute concentration play an important role, forming tighter enzyme.inhibitor
      complexes by binding to the large hydrophobic S2 pocket. The contrained
      conformers are thought to be resulted from intramolecular CH/pi interactions
      between a vinylic proton and the aromatic pi-electron cloud in the inhibitor
      molecules. These compounds constitute novel examples of the induced-fit binding
      inhibitor of possibly simplest structure.

PMID- 9547946
TI  - Effective lowly cytotoxic analogs of an HIV-cell fusion inhibitor, T22 ([Tyr5,12,
      Lys7]-polyphemusin II).
AB  - A tachyplesin peptide analog, T22 ([Tyr5,12, Lys7]-polyphemusin II), and its
      shortened congener, TW70 (des-[Cys8,13, Tyr9,12]-[D-Lys10, Pro11]-T22) have
      strong anti-human immunodeficiency virus (HIV) activity, comparable to that of 3'
      azido-2', 3'-dideoxythymidine (AZT). T22 and TW70 are extremely basic peptides,
      containing 5 Arg residues and 3 Lys residues. The number of positive charges
      might be related in part to high collateral cytotoxicities of T22 and TW70. Here
      we have synthesized several analogs, in which the number of positive charges has
      been reduced through amino acid substitutions using Glu or L-citrulline. As a
      result, several effective compounds have been found which possess higher
      selectivity indexes (SIs, 50% cytotoxic concentration/50% effective
      concentration) than those of T22 and TW70. Higher SIs were attributed mainly to a
      decrease in cytotoxicity.

PMID- 9547948
TI  - Mood disorders following traumatic brain injury: identifying the extent of the
      problem and the people at risk.
AB  - The extent of mood disorders following traumatic brain injury (TBI), and the
      possible risk factors, are investigated. New data are presented from a
      prospective study of consecutive hospital admissions. Six months post-TBI, 99
      adults completed a standardized assessment of emotional state, the Wimbledon Self
      Report Scale. Cognitive performance and the impact of the injury on everyday
      functioning were also assessed. The rate of clinically significant mood disorders
      (caseness) was 38%. Of the demographic or injury characteristics, only pre-injury
      occupational status predicted post-injury caseness. Those unoccupied pre-injury
      were more likely to report mood disturbance post-injury. In contrast, post-injury
      occupational status was not related to caseness either for the whole group or the
      subgroup of those previously occupied, despite the adverse effects on
      occupational functioning for a significant proportion of subjects. Associations
      were found between emotional state and cognitive and everyday functioning 6
      months post-injury. Psychosocial disabilities appeared more strongly associated
      to mood disorders than did physical disabilities. A significant level of unmet
      need has been highlighted, and possible risk factors identified, which may inform
      the purchase and provision of TBI rehabilitation services. Follow-up data on
      these subjects are available and will be reported separately.

PMID- 9547949
TI  - Clinical evaluation of the InnerSpace fibreoptic intracranial pressure monitoring
      device.
AB  - OBJECTIVE: The aim of this study is the clinical evaluation of the
      intraparenchymal ICP monitor InnerSpace OPX 100. METHODS: Sixty-four Inner Space
      OPX 100 transducers in 51 patients with severe head injury (42), intracranial
      spontaneous bleeding (6) or hypoxia (3) were studied. The transducer was placed
      in the frontal white matter. Thirty-nine patients received one catheter, eleven
      patients two catheters and one patient three catheters. The study period ranged
      from 10 hours-25 days; total study time was 421.5 days (mean duration 6.6 days).
      RESULTS: In nine cases (14.1%) an inadequate location of the ICP transducer was
      found, but the accuracy of the measurement was not influenced. Dislocation of the
      transducer occurred in eight cases (12.5%) due to inadequate handling. A failed
      transducer was observed in four cases (6.3%) because of a damaged optical fibre
      (1) or inadequate handling (3). In one patient (1.9%) a minor local infection
      developed. In eleven cases (17%) a haematoma around the ICP sensor was observed.
      Six haematomas were small; five haematomas were larger than 1 cm in diameter. In
      two patients a large frontal haematoma developed after exchange of the
      transducer. Operative evacuation was necessary in both cases. Zero shift was
      below 2 mmHg in all catheters. CONCLUSION: It is concluded that the InnerSpace
      intraparenchymal ICP monitor is a reliable device: the rate of catheter related
      intracerebral haematomas, however, is not acceptable. This could be improved by a
      better fixation of the catheter in the burr hole in order to avoid micromovements
      of the transducer.

PMID- 9547951
TI  - Prevalence of traumatic brain injury in psychiatric and non-psychiatric subjects.
AB  - Traumatic brain injury (TBI) and its sequelae may impact the expression and
      treatment of psychiatric disorders. The prevalence of TBI in psychiatric patients
      is unknown and investigations in the general population are limited. This study
      examined the prevalence of TBI with loss of consciousness in mental health
      setting patients (n = 231), general hospital and university staff and students (n
      = 534) and non-psychiatric medical clinical patients (n = 59). The Traumatic
      Brain Injury Questionnaire was used to assess TBI. A greater percentage of
      psychiatric patients reported TBI than medical patients or staff and students.
      Traumatic brain injuries were typically mild--moderate, medical assistance was
      frequently sought and use of alcohol and drugs was reported in a minority of TBI
      incidents. Multiple injuries were most common in psychiatric patients. The
      percentage of medical patients and staff and students reporting TBI was similar
      to previous research. The greater percentage of psychiatric patients reporting
      TBI indicates the need to assess TBI in this population. The role of TBI in the
      emergence, expression and treatment outcome of psychiatric disorders and the risk
      factors that leave psychiatric patients vulnerable to TBI should be further
      examined.

PMID- 9547950
TI  - Interpretive risks: the use of the Hopkins Symptom Checklist 90-Revised (SCL 90
      R) with brain tumour patients.
AB  - Patients with brain tumours often report distress. Interpretive problems ensue
      when measures normed on healthy persons are utilized to quantify distress. This
      study investigated potentially spurious elevations on the Hopkins Symptom
      Checklist 90 Revised (SCL 90-R). Responses of 17 patients were obtained prior to
      aggressive chemotherapy. Traditional interpretation indicated that 47% of the
      patients endorsed clinical levels of somatization, 53% obsessive-compulsive and
      59% psychotic disorders. Elevations were attributable to common consequences of
      brain tumours, medication and the emotional reaction to prognosis. Conventional
      interpretation would lead to inappropriate classifications. The majority of SCL
      90-R item endorsements were significantly different than those of the norm group.
      Appropriate interpretation of scores is discussed.

PMID- 9547952
TI  - Community-based training after acquired brain injury: preliminary findings.
AB  - Persons entering or returning to the workforce after brain injury often require
      assistance to identify, locate, secure and maintain employment. This is
      especially true for workers from economically disadvantaged environments who may
      have limited pre-injury work experience. Supported employment, the use of natural
      supports, and community-based approaches are helpful for the process of
      identifying, securing and maintaining work. However, reports are limited as to
      how these approaches are helpful for economically disadvantaged persons,
      especially in identifying meaningful work. An approach is described here which
      combines work adjustment training and supported employment; which is helpful in
      identifying consumer interest, and in improving position attainment, job
      retention and work satisfaction. A sample of persons (n = 38) with brain injury
      were contacted after completing the programme. A total of 59% of these persons
      remained employed at follow-up, compared to 32% at time of injury. Additional
      outcome data are presented to describe the usefulness of this approach.

PMID- 9547953
TI  - Caregiver burden at 6 months following severe traumatic brain injury.
AB  - Sixty-nine primary caregivers of people with a severe traumatic brain injury
      (TBI) were assessed at 6 months post injury. Caregivers completed questionnaires
      on the physical, cognitive, emotional, behavioural, and social functioning of the
      persons with the TBI. Caregiver psychosocial functioning and levels of subjective
      and objective burden were also assessed. Clinically significant levels of
      anxiety, depression, and impairment in social adjustment were evident in over a
      third of the caregivers. The frequency with which various changes in the person
      with the TBI and types of objective burden were reported had little relationship
      to the degree of distress caused by these changes. The person with TBI's social
      isolation and negative emotional behaviours caused the greatest degree of stress
      for caregivers. Caregivers were also most distressed by the impact that
      caregiving had on their personal health and free time. The results from a
      multiple regression analysis suggest that it is the presence of behavioural
      problems in the person with the TBI that has the most severe and pervasive impact
      on all aspects of caregiver functioning. It is suggested that these findings be
      taken into account when providing rehabilitation services to people with TBI and
      their families.

PMID- 9547954
TI  - Hypoxic brain injury with motor apraxia following an anaphylactic reaction to
      hymenoptera venom.
AB  - Hypoxic brain injury can be a complication following several well known
      situations or disorders. The neurological and neuropsychological characteristics
      of patients who suffer hypoxic brain injury depend on the mechanism of injury and
      the structures of the brain that are particularly vulnerable to hypoxia. Injury
      to the hippocampus with resultant memory impairment is a well described clinical
      feature. Motor apraxia has not been described as a common feature following
      hypoxic injury. This paper describes an unusual case of hypoxic brain injury that
      resulted from an anaphylactic reaction to hymenoptera venom. The patient
      presented with severe ideomotor apraxia as he emerged from coma after
      cardiorespiratory arrest. Surprisingly, the patients memory was relatively
      preserved in relation to other cognitive impairments. A brief discussion of the
      pathophysiology of hypoxic brain injury and the patient's rehabilitation outcome
      is presented.

PMID- 9547955
TI  - The empowering of Hong Kong Chinese families with a brain damaged member: its
      investigation and measurement.
AB  - This is an increasing recognition of the influential roles played by the families
      of brain damaged persons in rehabilitation. Although these families are expected
      to take up the burden of care, they are usually ill-prepared to face this long
      term process. This preliminary study of empowerment is aimed at helping Hong Kong
      Chinese families with a brain damaged member to regain a sense of mastery over
      the brain damage, their environment and their lives. The impact of brain damage
      on families was explored in order to propose a model to guide the development of
      assessment and intervention, as well as for the justification of practice by
      health care professionals. A 52-item instrument, the empowerment questionnaire,
      was developed through explorative factor analysis of responses of 211 families
      that included a brain damaged member. This analysis yielded four interpretable
      factors: efficacy: knowledge: support and aspiration and they demonstrated high
      validity reliability.

PMID- 9547956
TI  - Mothers, daughters and dieting: investigating the transmission of weight control.
AB  - OBJECTIVES: Research by Pike & Rodin (1991) found higher levels of weight concern
      and dissatisfaction with family functioning in mothers of eating disordered
      adolescent girls. The present study sought to extend this research by examining
      the maternal influences on weight and dieting concerns at a younger age. DESIGN:
      A cross-sectional comparison of high and low dietary restraint girls and their
      mothers was used. METHODS: Two groups of 20 11-year-old girls and their mothers
      completed assessments of dietary restraint, body shape preference, self
      perception, family functioning and body weight and height. RESULTS: Mothers of
      high restraint girls did not differ from comparison mothers in their current
      level of dieting, but did report more between-meal snacking and fasting. In
      addition, they rated their daughters' attractiveness significantly lower than the
      other mothers. Furthermore, families with a highly restrained daughter scored
      significantly lower on perceived family cohesion, organization and moral
      religious emphasis. CONCLUSIONS: The parallel with the findings of Pike & Rodin
      supports the role that mothers may play in the transmission of cultural values
      regarding weight, shape and appearance. Importantly, it also places early dieting
      within a wider context of dissatisfaction with family functioning.

PMID- 9547957
TI  - The value of the Rivermead Behavioural Memory Test (Children's Version) in an
      epidemiological study of older adults with Down syndrome.
AB  - The Rivermead Behavioural Memory Test for Children (RBMT-C) was used to assess a
      population-based sample of 74 people with Down syndrome (DS) aged 30 years and
      over (range 30-65 years) living in the Cambridge health district. Given the high
      age-specific risk of Alzheimer-like neuropathology in people with DS, the aim of
      this study was to determine whether this test provided a suitable measure of
      memory function in an older population of adults with DS who were at the age of
      risk for Alzheimer's disease. We also investigated whether there was a
      significant difference in everyday memory performance between different age,
      gender and day-centre groups. The level of learning disability in our sample
      ranged from mild, through severe to profound. Individuals with severe or profound
      learning disability were virtually untestable on this and other cognitive tests,
      but for the remaining two-thirds of the group, the RBMT-C could be used to assess
      memory function. Significant differences in memory function were found between
      younger (30-44 years) and older (45+ years) participants. Performance also varied
      between groups (e.g. from different day centres), illustrating the importance of
      population-based samples when determining the value of such tests. Ongoing
      longitudinal studies are required to establish the extent to which the RBMT-C is
      useful in assessing change in retrospective and prospective memory.

PMID- 9547958
TI  - Simulating a memory impairment: can amnesics implicitly outperform simulators?
AB  - OBJECTIVES: The purpose of this study was to examine the effectiveness of a
      variety of tests in differentiating simulating test performances from genuine
      memory-impaired and normal (control) test performances. DESIGN: A simulation
      design was implemented, based on an analogue design in which normal participants
      were given experimental instructions to feign a mental impairment and are
      compared to (a) other normal participants with instructions to perform honestly,
      and (b) a comparison group, for example, acquired brain-injured persons, with
      similar instructions. METHOD: Forty individuals comprised the simulating and
      control group and all participants were randomly assigned to the simulating and
      control groups. Twenty memory-impaired patients, all of whom had been diagnosed
      as suffering from a memory impairment following acquired brain damage,
      participated as the memory-impaired control group. The simulation group was
      directed to imitate a person with a memory impairment. The primary outcome
      measure involved identifying those tests, if any, where simulators were
      significantly different from normal and memory-impaired participants. RESULTS: On
      5 of the 15 tasks administered, simulators performed significantly differently
      from normal and memory-impaired participants. Of these 5 tasks, the coin-in-the
      hand, when administered in conjunction with the autobiographical interview,
      identified 95 per cent of the simulators without misclassifying any of the memory
      impaired or normal participants. CONCLUSION: It is suggested that these two
      tests, when administered jointly, might be of use in clinical settings to assist
      in the detection of malingerers.

PMID- 9547959
TI  - Do chronic pain patients 'Stroop' on pain stimuli?
AB  - OBJECTIVES: Two experiments investigating the presence of information-processing
      biases on tasks of attention (Stroop task) and memory (free recall) in relation
      to mood states in chronic pain patients are reported. The first investigates
      whether previously reported attentional bias is a function of pain status or mood
      state. The second describes a more detailed examination of the roles of anxiety
      and depression in processing biases in chronic pain patients. DESIGN AND METHOD:
      Both studies compared interference time on an emotional Stroop task between
      chronic pain patients and controls. Other measures included self-report of pain,
      depression and anxiety. RESULTS: Neither study found evidence for an attentional
      bias, although a memory recall bias was demonstrated. CONCLUSIONS: Interference
      in attending to emotionally salient stimuli appears to be related to measures of
      anxiety and depression rather than pain per se. When added to the findings of
      other investigators, these results suggest that the presence of attentional
      biases in chronic pain patients can best be accounted for as arising from mood
      state rather than pain-patient status.

PMID- 9547960
TI  - Care staff responses to people with learning disabilities and challenging
      behaviour: a cognitive-emotional analysis.
AB  - This study explores the application of Weiner's cognitive-emotional model of
      helping behaviour to care staff responses to challenging behaviour of people with
      learning disabilities. Participants were 20 residential care staff who worked
      with people with challenging behaviour and 20 who did not. Six examples of
      challenging behaviour were presented, and for each behaviour participants were
      asked to give a probable cause, rate attributions of stability, internality,
      globality and controllability for their cause, their optimism for change of the
      behaviour, their evaluation of the behaviour and a person showing the behaviour,
      their emotional response to the behaviour and their willingness to put extra
      effort in to helping change the behaviour. Data were analysed using correlation
      and regression methods. Carers working with people with challenging behaviour
      were more likely to evaluate the person more positively and report they would be
      more likely to offer extra effort in helping. A path analysis showed that helping
      behaviour was best predicted by optimism, which was best predicted by negative
      emotion which was best predicted by the attribution of controllability. We
      conclude that attributions and emotions reported by carers in response to
      challenging behaviour are consistent with Weiner's cognitive-emotional model of
      helping behaviour. Formulating carer behaviour using such models offers the
      possibility of using cognitive-behavioural methods in working with staff beliefs,
      emotions and behaviour in response to challenging behaviour.

PMID- 9547961
TI  - Behavioural effects of long-term multi-sensory stimulation.
AB  - OBJECTIVES: Regular access to a multi-sensory environment (MSE or Snoezelen room)
      was compared with a non-complex sensory environment for individuals with learning
      disabilities. We also tested the prediction that those individuals whose
      challenging behaviour was maintained by sensory consequences would benefit most
      from exposure to the MSE. DESIGN: The conditions were compared over 16-week
      periods using a double crossover design, and were matched for social contact and
      attention from the enabler. Participants were randomly assigned to orders of
      treatments. METHODS: Participants were 27 adults with severe/profound learning
      disabilities who exhibited challenging behaviour. Behaviour was assessed before
      and after each treatment phase using both direct observation and standardized
      assessments (the Functional Performance Record and the Problem Behaviour
      Inventory). The behavioural observations formed the basis of a functional
      analysis of each individual's challenging behaviour. RESULTS: Some participants
      became more calm and relaxed while in the MSE, however, the objective measures of
      behaviour outside the treatment settings revealed no difference between the MSE
      and control conditions. Challenging behaviour maintained by sensory consequences
      showed no greater responsivity to the MSE than to the control condition.
      CONCLUSIONS: The multi-sensory environment had no effects beyond those that could
      be ascribed to the social interaction between participant and enabler. Anecdotal
      evidence of favourable responses within the MSE itself could not be confirmed
      outside the environment.

PMID- 9547962
TI  - The treatment of six men with a learning disability convicted of sex offences
      with children.
AB  - This paper describes a cognitive therapy for men with a learning disability
      convicted of sex offences against children. Methods are described which focus the
      session, emphasize confidentiality, ensure that the patient accepts
      responsibility for the offence, and deal with issues of intent, harm done to the
      victim and sequences of offending behaviour. Methods for producing cognitive
      change are described. Patients were assessed regularly and data are presented in
      detail. While all six men showed improvement, there were several variables which
      interfered with the course of treatment. The study attempts to address two major
      problems in work with sex offenders: the difficulty of employing a controlled
      treatment design and the importance of a long follow-up period.

PMID- 9547963
TI  - Malingering of memory impairment on the Colorado Priming Test.
AB  - OBJECTIVES: We hypothesized that simulated malingerers would show a weaker
      priming effect and a longer response latency than control patients and patients
      with a brain injury on a priming test. DESIGN: Participants were compared on
      their performance on the Colorado Priming Test to replicate and extend the
      original validation study. METHODS: Of 33 participants, 16 were people with a
      brain injury and 17 were non-head injured control patients who were also
      instructed to feign cognitive impairment (simulators N = 17). RESULTS: Up to 88
      per cent of simulating malingerers and 75 per cent of head-injured participants
      were correctly classified. CONCLUSIONS: The Colorado Priming Test may be useful
      in identifying patients feigning memory impairment.

PMID- 9547964
TI  - Cognitive inhibition in phobia.
AB  - OBJECTIVES: The purpose of this study was to investigate whether cognitive bias
      for threat in anxious individuals may be attributed to a defective inhibition.
      DESIGN: It was investigated whether phobics and not non-phobics would show a
      defective inhibition of threat words as compared to neutral words. METHOD:
      Inhibition was measured by a negative priming task, which was administered to
      spider phobic participants (N = 29) and non-phobic controls (N = 31). RESULTS:
      The phobics did not show less negative priming of threatening information.
      Instead, they showed a general delay on all probe displays that were presented
      after threatening primes. CONCLUSION: Anxiety is related to defective inhibition
      of threat, in the sense that this inhibition consumes extra cognitive resources.

PMID- 9547965
TI  - Oxford-Liverpool Inventory of Feelings and Experiences: reliability in an
      experimental population.
AB  - Further to the recent development of the Oxford-Liverpool Inventory of Feelings
      and Experiences (O-LIFE), a short multidimensional schizotypy questionnaire, the
      present study set out to identify the reliability of all scales of this
      questionnaire within the same population. Participants were required to complete
      the O-LIFE on two separate occasions, whilst taking part in latent inhibition and
      negative priming experiments. All scales correlated highly, thus lending further
      support to the reliability of this time efficient questionnaire.

PMID- 9547966
TI  - Changes following community living skills training: a controlled study.
AB  - Fifty-seven adults with mild to moderate learning disability served as
      participants in a community living skills training programme. Twenty-nine were
      trained using in vivo techniques, 13 were taught using classroom techniques and
      15 acted as a no treatment control group. Assessments of community living skills
      and adaptive behaviour found those receiving in vivo training performed
      significantly better than the other groups. Eventual placement in the community
      reflected this superiority.

PMID- 9547967
TI  - A long-term follow-up study of a cohort of referrals to an adult mental health
      clinical psychology department.
AB  - The study, using the SCL-90-R, investigated the long-term outcome of clinical
      psychology interventions with adults by contacting 95 clients between five and
      eight years after initial contact. Post-treatment improvements in global
      psychological well-being were generally maintained at long-term follow-up. About
      a quarter of clients, however, did not report any improvement in the initial
      problem and about a half had received help from other services since ending
      contact with the department. The study provides encouraging evidence of long-term
      benefits for many clients, but we suggest a reconsideration of the optimal
      provision of psychological help for people whose problems may be enduring and/or
      recurrent.

PMID- 9547968
TI  - Early experiences with the Tip-Edge appliance.

PMID- 9547969
TI  - Orthodontic reconstruction in a victim of murder.
AB  - Accurate comparison of ante-mortem photographs and the skull of a deceased person
      is dependent upon suitable superimposition techniques and a post-mortem dentition
      which is comparable to the situation obtaining in the individual at the time of
      death. The skull featuring in this case presented with a missing upper lateral
      incisor, lost after death, and the occlusion was studied enabling a replacement
      tooth to be provided and positioned as in life. Although no dental records were
      available, good quality photographs of a putative identity were compared by
      electronic superimposition and the restored occlusal characteristics of the skull
      were shown to accurately match the photographs of one possible victim. This
      evidence resulted in positive identification by a Coroner. This case illustrates
      the importance of seeking specialist clinical advice in forensic dental cases.

PMID- 9547970
TI  - Applications of Scanora multimodal maxillofacial imaging in orthodontics.
AB  - The principles of the Scanora multimodal radiography system are described. This
      self-contained unit of X-ray generator, patient chair, and imaging elements
      incorporates the two basic principles of narrow beam radiography and spiral
      tomography. Conventional panoramic images or magnified images of the dentition
      can be produced. In orthodontics, the application of spiral tomography in order
      to obtain cross sectional images has proved helpful in the assessment of a number
      of patients. Four cases are reported in which the images obtained using this
      system has substantially contributed to their management.

PMID- 9547971
TI  - The Clinical Standards Advisory Group (CSAG) Cleft Lip and Palate Study.
AB  - A national study of care and outcomes in children born with a unilateral cleft
      lip and palate (UCLP) was performed over a 15-month period. Two cohorts of
      children ('5-year-olds' and '12-year-olds') were examined. There were 57 active
      cleft teams in the U.K. with 105 consultant orthodontists involved in the care of
      these children. Only 36 teams could provide basic data such as patients names. Of
      the patients, 47-51 per cent had neonatal appliances. The dental arch
      relationships were measured with the Goslon Index and a Five-Year-Old Index, 37
      39 per cent of both age groups were either 'poor' or 'very poor'. Seventy per
      cent of the 12-year-old patients had a Skeletal III relation and 42 per cent of
      bone grafts were seriously deficient or failed. Dental treatment for active
      caries was needed by 40 per cent of 5-year-olds and 20 per cent of 12-year-olds.
      In addition, the training of recently appointed consultant orthodontists involved
      in the care of these children was scrutinized. As a whole, the results were
      disappointing with standards of care not significantly raised in the last decade.
      Recommendations have been made to the Department of Health and the implications
      for the orthodontic profession are explored. Overall, it seems that fewer
      orthodontists will need to be involved in a centralized care model for these
      children.

PMID- 9547972
TI  - Assessing malocclusion--the time factor.
AB  - Assessment of occlusal status for orthodontic purposes may be undertaken by
      subjective assessment or by means of an index of occlusion. The assessment method
      should be reproducible and should achieve the intended outcomes. This study
      investigated another possible modifying factor--performance over time.
      Photographs and dental casts of 45 subjects at 12 years of age were compared with
      follow-up records at 16 years of age. No orthodontic intervention had occurred
      during the 4 years. Subjective severity assessments and Aesthetic Component (AC)
      scores of the Index of Treatment Need (IOTN) for first and second series records
      were made by four orthodontists. Scores of the Dental Aesthetic Index (DAI) and
      Dental Health Component (DHC) of the IOTN were made by one of the authors.
      Implications for hypothetical decisions to treat were considered. There was a
      significant reduction in the subjective severity and DAI scores across the whole
      sample and in the mixed dentition subgroup. There was a non-significant reduction
      in the AC (IOTN) scores across the whole samples, but there was a significant
      reduction in the AC (IOTN) scores in the mixed dentition subgroup. The DHC (IOTN)
      categorisations proved to be more stable over the period of study.

PMID- 9547973
TI  - An ex vivo investigation into the effects of chemical solvents on the debond
      behaviour of ceramic orthodontic brackets.
AB  - The problems of ceramic bracket debond have been well documented. A peppermint
      oil material has been marketed previously as a debonding agent. This study
      assessed ex vivo the effects of peppermint oil application on the debond
      behaviour of ceramic brackets compared with ethanol and acetone which are
      recognized softening agents. Intrigue brackets were bonded to 100 extracted
      premolar teeth. Groups of 20 bonded teeth were then placed in a test solution,
      control (distilled water), peppermint oil (5 minutes and 1 hour), acetone (1
      hour), and ethanol (1 hour). The teeth were debonded using an Instron. Universal
      Testing Machine and debond forces recorded. The site of bond failure along with
      the adhesive remnant index was recorded for each tooth. One hour placement in
      peppermint oil produced the lowest mean and maximal debond forces (77 and 114 N,
      respectively). Weibull analysis showed that the probability of failure at 100 N
      was increased for the 1-hour peppermint group at 88 per cent compared with 52 per
      cent for the control. Placement in peppermint oil produced the lowest levels of
      retained resin. There was no evidence of enamel fracture with any of the groups,
      but bracket fracture remained a problem.

PMID- 9547974
TI  - Parental perceptions and attitudes on orthodontic care.
AB  - The objective of this paper is to determine whether an association existed
      between parents' attitudes to orthodontic issues affecting themselves and their
      attitudes to possible orthodontic treatment for their child. It consisted of an
      analytical survey using a self-administered questionnaire, taken in South East
      England of six-hundred parents of children aged 9 years. The questionnaires were
      delivered to the parent with the help of their child's school. Four-hundred-and
      thirty-seven questionnaires were returned (73 per cent). Significant associations
      were found between desire by the parents for orthodontic treatment for themselves
      and perception of need in their child, parental satisfaction with own dental
      appearance and perception of need in their child, a parental history of
      orthodontic treatment and a determination to insist on their child's co-operation
      with orthodontic treatment. Logistic regression models show the odds of parents
      who desire orthodontic treatment themselves, perceiving need in their children
      are three times greater than for other parents. 1. There is some evidence that
      parents who desire orthodontic treatment for themselves, or who are former
      orthodontic patients are more likely to approve of orthodontic care in principle
      and to perceive a need for it in their child. 2. Further research is required to
      establish to what extent genetic factors are involved.

PMID- 9547976
TI  - Toothbrushes.

PMID- 9547977
TI  - How UK orthodontists advise patients on oral hygiene.
AB  - In 1993, 1038 UK orthodontists (all the members of the British Association of
      Orthodontists and the British Society for the Study of Orthodontics) were asked
      by questionnaire about the oral hygiene advice they gave to patients undergoing
      routine orthodontic treatment. All the orthodontists gave advice on tooth
      brushing. Most (89.5 per cent) gave dietary advice and (84 per cent) used
      disclosing tablets. A fluoride rinse was recommended by 73 per cent and a
      chlorhexidine mouthwash by 41.9 per cent. Many orthodontists advocate appropriate
      oral hygiene measures, but the efficacy of such methods is determined by the
      patient's motivation. The orthodontist therefore requires skills in behavioural
      management. Oral hygiene measures may be more cost-effective when undertaken by
      trained auxiliaries.

PMID- 9547975
TI  - A critical assessment of high-earning orthodontists in the General Dental
      Services of England and Wales (1990-1991)
AB  - Cases from the Dental Practice Board's 2 per cent random sample of completed
      cases which had been treated by orthodontic practitioners with high gross
      earnings, were compared to all the cases within the sample from other
      practitioners. They were assessed using the PAR index and IOTN. High earning
      orthodontists treated slightly more cases with lower objective need for
      treatment, but treated no more cases 'Unnecessarily' than other practitioners.
      They used more fixed appliances, and had marginally better levels of residual
      need for treatment at finish, although this was at least partially explained by
      lower levels at start. Generally, their standards were not substantially
      different to other practitioners. Appliance type had a marked effect on outcome,
      as did levels of malocclusion and need for treatment at start. Both groups of
      practitioners performed similarly (better) with dual arch fixed appliances:
      however, overall standards could only be described as mediocre. There is no
      justification to single out high earning orthodontists for special scrutiny.
      However, it may be beneficial if the system of remuneration in the General Dental
      Services could be modified to give more positive incentive to quality, rather
      than simply quantity of treatments.

PMID- 9547978
TI  - Re: A life threatening complication of removable appliance therapy?

PMID- 9547979
TI  - Re: Risk assessment.

PMID- 9547980
TI  - Orthodontics in Spain--at the crossroads.

PMID- 9547981
TI  - Orthodontic postgraduate training in Germany--have we anything to learn?
AB  - In 1996, the authors were able to visit the University Orthodontic Unit in
      Marburg, Germany. Author FL was able to undertake the visit as part of a
      discretionary secondment for specialist training and this article describes the
      author's (FL) experience of orthodontic, postgraduate training there, and
      highlights differences between training in the U.K. and Germany. In the current
      climate of change with regard to specialist training, it seemed timely to
      investigate how training occurs elsewhere in Europe.

PMID- 9547982
TI  - Lymphoma. Introduction.

PMID- 9547983
TI  - FISH and related techniques in the diagnosis of lymphoma.
AB  - Many malignant lymphomas are characterized by recurrent genetic abnormalities.
      These include numerical abnormalities, deletions and reciprocal translocations.
      In this chapter, we have focused on the detection of chromosomal translocations
      in B cell lymphomas and discussed some trisomies in lymphomas and CLL. FISH is a
      well developed molecular method by which it is possible to detect numerical and
      structural chromosomal abnormalities. We addressed various aspects of metaphase,
      and especially interphase, FISH and also described the recently developed DNA
      fibre FISH technology. Using this method, it is possible simultaneously to detect
      and map chromosomal breakpoints. FISH is also compared with more conventional
      detection methods such as banding analysis, Southern blot analysis and PCR for
      the translocations t(8;14) and variant translocations in Burkitt's lymphoma,
      t(14;18) in follicular lymphoma and t(11;14) in MCL. Other breakpoints in B cell
      lymphoma are also discussed. It might be concluded that the rapid development in
      interphase and DNA fibre FISH will provide us with quick, easy and cheap tools to
      identify specific chromosomal translocations and other genomic abnormalities in
      human tumours.

PMID- 9547984
TI  - Polymerase chain reaction in the assessment of lymphomas.
AB  - The polymerase chain reaction (PCR) offers a practical means of studying the
      molecular genetic features of lymphomas. The method is rapid and, as formalin
      fixed, paraffin processed samples can be used, does not require special tissue
      handling procedures. PCR amplified immunoglobulin and T cell receptor gene
      rearrangements can be exploited as markers of clonality and lineage and genetic
      abnormalities such as chromosome translocations and mutations of oncogenes and
      tumour suppressor genes can be used to identify specific lymphoma types.
      Polymorphic X linked loci may also be used as markers of clonality in females.
      Direct sequencing of PCR amplified IGH variable regions has provided insights
      into the developmental stages, susceptibility to antigen drive and dissemination
      patterns of lymphomas. The role of oncogenes and tumour suppressor genes such as
      MYC and TP53 in lymphomas can be studied by PCR amplification of mutation
      hotspots and direct sequencing of products. Known viral and bacterial DNA can
      readily be identified using PCR and unknown organisms sought using conserved
      primers to amplify polymorphic sequences. PCR analysis of the lymphomas and
      related disorders has accelerated our understanding of their molecular biology
      and provides a practical tool with diagnostic and prognostic applications. Future
      development of in situ PCR methods will provide cellular localization of genetic
      defects and infectious agents.

PMID- 9547985
TI  - Molecular single cell studies of normal and transformed lymphocytes.
AB  - The polymerase chain reaction allows the characterization of RNA and DNA
      sequences from single cells. Methods were established to analyse single cells
      isolated from suspension or by multicolour flow cytometry. We established a
      method to isolate single immunostained cells from frozen tissue sections and to
      analyse those cells for immunoglobulin gene rearrangements. This method was first
      used to study B cell differentiation within human germinal centres. In another
      series of experiments, Hodgkin and Reed-Sternberg (HRS) cells from a total of 14
      cases of HD were analysed for B lineage derivation and clonality. In 13 of the 14
      cases, clonal V gene rearrangements were identified. This shows that HRS cells
      generally represent the outgrowth of a clonal population of B cells. The
      detection of somatic mutations in all VH gene rearrangements amplified from HRS
      cells and the nature of those mutations identifies a GC B cell as the HRS
      precursor.

PMID- 9547986
TI  - The NPM/ALK gene fusion in the pathogenesis of anaplastic large cell lymphoma.
AB  - The cloning of the t(2;5) translocation breakpoints and the identification of the
      NPM/ALK fusion in Ki-1 ALCL have brought forth from this heterogeneous
      morphological grouping a subset of cases defined by an aetiological genetic
      alteration. The analysis of NPM/ALK positive lymphomas as a single
      clinicopathological entity has already begun to clarify and explain some previous
      clinical observations in Ki-1 ALCL. It has also confirmed that HD is
      pathogenetically unrelated to NPM/ALK positive Ki-1 ALCL. This is yet another
      example of the overall nosological evolution from morphological entities to
      pathogenetic entities among lymphomas, leukaemias and, more recently, sarcomas.
      Although much work remains to be done on the mechanism of NPM/ALK
      lymphomagenesis, rational treatment approaches are now within reach. Such novel
      approaches could target NPM/ALK at the level of the genomic sequence, transcript,
      protein or its downstream targets, when the latter are further elucidated.
      Systems developed to inhibit other fusion transcripts and oncogenic tyrosine
      kinases can now be applied to NPM/ALK positive lymphomas. Furthermore, the strong
      and highly selective surface expression of CD30 in Ki-1 ALCL may provide a basis
      for the targeted delivery of these novel therapeutic agents.

PMID- 9547987
TI  - Anaplastic large cell lymphoma and its morphological variants.
AB  - Clinicopathological studies have identified CD30+ ALCL as a clinicopathological
      entity with heterogeneous morphology and a frequent translocation involving
      t(2;5), with a better prognosis than most other T cell neoplasms and a different
      natural history and prognosis than Hodgkin's disease. Because of the different
      natural history and prognosis of CD30+ ALCL, it is important to recognize this
      entity and its morphological variants. Further studies are indicated to determine
      whether specific clinical management(s) and therapies are necessary for variants
      of ALCL such as HD like ALCL and the small cell predominant type.

PMID- 9547988
TI  - The interface of Hodgkin's disease and anaplastic large cell lymphoma.
AB  - We reviewed 18 cases in which morphology was intermediate between Hodgkin's
      disease (HD) and anaplastic large cell lymphoma (ALCL). Eight cases exhibited the
      usual CD30+, CD15+/-, null cell phenotype of classic HD but were rich in
      neoplastic cells with sinusoidal infiltrating pattern. In this group, there was
      no expression of antigens (EMA, BNH9, CBF78) associated with ALCL, and only two
      were positive for Epstein-Barr virus (EBV). Ten EBV negative cases fit the
      description of HD like ALCL by variable expression of antigens unassociated with
      HD. EMA was clearly and strongly expressed in all ten, whereas antigens
      recognized by BNH9 and CBF78 were expressed in four and three cases,
      respectively. Focal expression of CD45 and CD43 was observed in half of these
      cases. In only one case was the t(2.5) translocation detected with the new
      monoclonal antibody, ALK1. Therefore, the expression of EMA, BNH9 and CBF78,
      often in concert without CD15 and without the specific translocation, appears
      currently to be the most probable phenotype and genotype of HD like ALCL. There
      was a tendency for aggressive behaviour of the disease considered HD like ALCL.
      Whether such patients will benefit from a therapeutic strategy that takes into
      account both phenotype and genotype remains to be discovered.

PMID- 9547990
TI  - Clonality in lymphocyte predominance Hodgkin's disease.
AB  - Abundant evidence has led to the clinical and biological separation of lymphocyte
      predominance from other types of Hodgkin's disease. However, it is still not
      clear whether lymphocyte predominance represents a polyclonal reactive lesion
      (possibly representing an abnormal immune disorder), a polyclonal or oligoclonal
      preneoplastic disorder or a monoclonal neoplastic disorder. The clinical and
      histological features are distinctive, but they do not provide clear indications
      of the nature of lymphocyte predominance. Some immunohistochemical and in situ
      hybridization studies have shown monotypic light chain restriction in the L&H
      cells, almost always of kappa type, implying a monoclonal process. Southern
      blotting studies are of limited utility, given their relatively low sensitivity
      and the rarity of L&H cells within involved tissues. Polymerase chain reaction
      studies have yielded conflicting results. Some, but not all, have demonstrated
      monoclonal populations in tissue extracts. Single cell PCR studies have generally
      not found monoclonal populations, although one case stands as an exception. Cases
      of large cell lymphoma complicating lymphocyte predominance have been monoclonal
      by polymerase chain reaction and clonospecific primers derived from these clones
      have demonstrated similar populations in the corresponding lymphocyte
      predominance tissues in some, but not all, studies.

PMID- 9547989
TI  - Molecular biology of Hodgkin's disease.
AB  - The mist surrounding the origin and genesis of HRS cells of classical HD is
      beginning to dissipate. Molecular biological studies of classical HD at the
      single cell level strongly suggest that the HRS cells in the majority of cases
      represent a monoclonal outgrowth of late germinal centre B cells that have lost
      their capacity to express IG through crippling mutations introduced during the
      germinal centre reaction. Because of the expression of T cell antigens and/or
      cytotoxic molecules, the HRS cells of a minority of classical HD cases appear to
      originate from T cells. Under physiological conditions, B cells that are unable
      to express IG are eliminated by apoptosis. In most B cell derived classical HD
      cases, the HRS cells have lost their IG gene coding capacity through mutation and
      should therefore die of apoptosis. Since this usually does not happen, blockade
      of the apoptotic pathway may be a major event in the pathogenesis of B cell
      related classical HD. It is tempting to assume that viruses such as EBV, as well
      as regulator genes that normally monitor the human genome for damaged DNA, such
      as TP53, might be involved in the postulated hindrance of the apoptotic pathway,
      leading to the genesis of classical HRS cells.

PMID- 9547991
TI  - Epstein-Barr virus infection and the pathogenesis of malignant lymphomas.
AB  - EBV is associated with an ever increasing number of human malignancies, which
      illustrates the importance of understanding how the virus contributes to
      tumorigenesis. Recent work has identified as set of EBV latent proteins that are
      indispensable for B cell transformation in vitro, and possible mechanisms of
      action are beginning to emerge for some of these proteins. In addition to viral
      gene expression, host factors appear to be involved in the development of virus
      associated tumours. Firstly, virus specific immunity is important for preventing
      the outgrowth of EBV associated tumours. Disturbances of EBV specific
      immunosurveillance can occur as a consequence of systemic immunosuppression or
      due to local factors, some of which may directly or indirectly result from the
      expression of EBV genes. Secondly, the phenotype of virus infected cells seems to
      be important. Thus, many EBV associated tumours appear to arise from cell types
      that do not represent a "physiological" target for the virus and thus may not be
      adapted to establishing asymptomatic persistent EBV infection. Furthermore, the
      function of transformation associated viral gene products may vary according to
      the cellular phenotype.

PMID- 9547992
TI  - Cytogenetic mechanisms in the pathogenesis and progression of follicular
      lymphoma.
AB  - A summary of the clinically significant cytogenetic markers in follicular
      lymphoma is presented in Table 3. It is clear that the use of cytogenetic
      analysis to evaluate progression and transformation in follicular lymphoma is
      complicated by the variety and complexity of the chromosomal aberrations present
      in this disease. Cytogenetic and molecular studies have indicated that the
      t(14;18) translocation is the prerequisite of a multistep process in the
      lymphomagenesis of follicular lymphoma; it is usually followed by a long
      quiescent period during which the B cell population expands and additional
      oncogenic mutations occur leading to eventual progression and transformation to a
      highly malignant form. This process can be accomplished by a variety of pathways:
      Activation of other oncogenes by additional chromosomal rearrangements (e.g. MYC,
      LAZ3) Deletion and mutation of tumour suppressive genes (e.g. TP53, proposed
      genes on 6q) Gain of whole or parts of chromosomes, leading to increased
      expression of important regulating factors (e.g. MDR and T cell receptor genes on
      chromosome 7) More studies are required to determine which of these pathways, if
      any, is most important for neoplastic transformation.

PMID- 9547993
TI  - Primary splenic lymphoma.
AB  - Although a number of lymphomas and leukaemias can involve the spleen and may
      present clinically with splenomegaly, only the B cell disorders SMZL and
      hepatosplenic gamma/delta T cell lymphoma can be considered true primary splenic
      lymphomas. The former is not uncommon and has histological features which may be
      to a certain extent recapitulated by other B cell lymphomas when they involve the
      spleen. In view of the characteristic clinically indolent behaviour of SMZL and
      its favourable response to splenectomy, rather than chemotherapy, the
      differential diagnosis from other B cell lymphomas is important. Hepatosplenic
      gamma/delta T cell lymphoma is rare; for the purpose of precise classification,
      it needs to be distinguished from other NK like T cell lymphomas and NK cells
      lymphomas that sometimes involve the spleen.

PMID- 9547994
TI  - Gastric MALT lymphoma and Helicobacter pylori.
AB  - The majority of low grade gastric lymphomas arise within acquired organized
      lymphoid tissue, which has all the features of MALT. This MALT is specifically
      acquired most commonly in response to infection of the gastric mucosa by H
      pylori. The lymphocytes within this MALT are therefore programmed to respond to
      this organism and the neoplastic cells of the lymphoma that may develop within
      this acquired MALT retain the ability to respond to the immunological
      proliferative drive associated with the continued presence of the organism.
      Following the removal of this immunological drive by eradication of the organism
      in vivo, the lymphoma shows clinical and histological regression. The time
      required to see this response is unknown and there are some lymphomas that fail
      to respond to simple Helicobacter eradication. In some cases, there is continued
      molecular evidence of the presence of the lymphoma clone in low levels and the
      significance of this remains unknown. These factors are presently under detailed
      examination, and several clinical trials to assess the response of a large series
      of low grade gastric MALT lymphomas to anti-Helicobacter therapy and the
      requirement for additional chemotherapy are at present in progress.

PMID- 9547996
TI  - Enteropathy associated T cell lymphoma.
AB  - Enteropathy associated T cell lymphoma (EATCL) is the most serious complication
      of coeliac disease. HLA genotyping shows that patients with EATCL have the
      coeliac disease associated DQA1*0501, DQB1*0201 phenotype. Other HLA-DR/DQ
      alleles that may be associated with adult onset coeliac disease appear to
      represent additional risk factors for lymphoma development. Increased numbers of
      small intestinal intraepithelial cytotoxic T cells are found in the small
      intestinal mucosa of patients with coeliac disease and in the enteropathic bowel
      of patients with EATCL. The neoplastic cells of EATCL have the immunophenotype of
      intraepithelial cytotoxic T cells and may exhibit epitheliotropism. Analysis of T
      cell receptor genes and immunohistochemistry have shown that the intestinal
      mucosa distant from the tumour contains clonal populations of small T cells,
      often of the same clone as the high grade T cell lymphoma. Most cases of chronic
      ulcerative enteritis are probably part of the same disease process. The
      ulceration seen in chronic ulcerative enteritis and in enteropathy associated T
      cell lymphoma may be due to the release of cytolytic enzymes by cytotoxic T cells
      and tumour cells. These findings suggest that EATCL arises in the setting of
      coeliac disease and evolves from intraepithelial lymphocytosis through low grade
      lymphoma to a high grade tumour, possibly under antigen drive from gliadin
      peptides. These peptides may be presented to the intraepithelial cytotoxic T
      cells directly by epithelial cells bearing the coeliac disease associated HLA-DQ
      alleles.

PMID- 9547995
TI  - Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications.
AB  - Lymphomatoid granulomatosis (LG) exhibits many similarities both clinically and
      pathologically to angiocentric T/NK cell lymphoma and was until recently
      considered to be part of the same disease spectrum. However, recent data indicate
      that LG is an EBV positive B cell proliferation associated with an exuberant T
      cell reaction. LG presents in extranodal sites, most commonly the lung
      (Katzenstein and Peiper, 1990). Other frequent sites of involvement include
      kidney, skin, central nervous system and liver. The pattern of necrosis in both
      LG and T/NK cell lymphoma is very similar, emphasizing the probable importance of
      EBV in mediating the vascular damage. Recent studies implicate the chemokines IP
      10 and Mig in the pathogenesis of the vascular damage. Although the predominant
      infiltrating cells are T cells, the T cell receptor genes are not clonally
      rearranged. However, by VDJ polymerase chain reaction, approximately 60% of cases
      contain clonal rearrangements. EBV sequences can be localized to B cells and are
      clonal in most cases. Most patients with LG when carefully evaluated clinically
      have defects in cytotoxic T cell function and reduced levels of CD8+ T cells. LG
      is also common in many immunodeficiency states, such as AIDS, Wiskott-Aldrich
      syndrome and post-transplantation immunodeficiency. Thus, in many respects, LG
      resembles an EBV driven lymphoproliferative disorder. Some cases of LG regress
      spontaneously, but most patients require therapy. Treatment approaches have
      included cyclophosphamide and prednisone, aggressive combination chemotherapy and
      interferon alpha 2b, because of its antiviral, antiproliferative and
      immunomodulatory effects.

PMID- 9547997
TI  - Lymphomas associated with HIV infection.
AB  - Lymphomagenesis in HIV positive patients is a complex phenomenon not yet
      completely understood (Karp and Broder, 1992). The great majority of NHL are of
      the B cell type. Burkitt lymphoma seems to develop early during the evolution of
      HIV infection in patients with a CD4 count above 200/microliter. MYC is
      rearranged in the majority of the cases. EBV latent infection is observed in 30
      45%. EBV status is characterized by a negativity for EBNA2 and LMP1 The main
      sites of the tumour are the lymph node and the bone marrow. Diffuse large cell
      lymphomas, mostly represented by immunoblastic lymphomas with plasmacytoid
      differentiation and by centroblastic lymphomas rich in immunoblasts, are a late
      event in HIV infection, in patients with a low CD4 count (often below
      50/microliter). The prognosis is worse than in Burkitt and Burkitt like lymphoma.
      MYC is rearranged in about 30-40% of the cases, whereas more than 70% are EBV
      positive. EBV status is characterized by a positivity for both EBNA2 and LMP1. B
      type ALC lymphomas are more frequently associated with EBV than in the general
      population and exhibit the same EBV status as diffuse large cell lymphomas. HD
      occurs at any stage of HIV infection. The majority of patients are in clinical
      stage III or IV at the time of diagnosis, and HIV associated HD shows a more
      aggressive course than non-HIV HD. Many cases remain difficult to classify;
      instead, the immunophenotype of neoplastic cells is similar to that in HD
      occurring in the general population. Histiocytes and epithelioid cells are even
      more numerous than T lymphocytes, and the CD4:CD8 ratio is low. Neoplastic cells
      are EBV positive in most or all cases, although they are consistently HIV
      negative by in situ hybridization. Lymphomagenesis seems to be very complex, with
      multiple agents acting together or successively. EBV, other viruses,
      rearrangement of various genes and production of cytokines all seem to have major
      roles in addition to immune deficiency.

PMID- 9547998
TI  - Targeted antibodies in the treatment of lymphomas.
AB  - Monoclonal antibodies coupled to drugs and toxic agents (immunotoxins) or
      radionuclides (radioimmunoconjugates) represent new tools for immunotherapy of
      haematological malignancies. Immunotoxins constructed with toxins of either plant
      or bacterial origin have shown a powerful antitumor activity both in vitro and in
      mice with severe combined immunodeficiency bearing various kinds of leukaemias
      and lymphomas. Preliminary clinical trials have shown an activity of these
      compounds at least in a proportion of patients. However, tumour responses have
      generally been partial and transient. The main problems with immunotoxin therapy
      remain the inability of immunotoxins to target tumour cells in the presence of a
      high burden of disease, the host immune response against both the antibody and
      the toxin moieties, which precludes repeated administration of immunotoxins, and
      the vascular leak syndrome. Targeting of tumour cells with specific antibodies
      armed with radionuclides (usually iodine-131 or yttrium-90) appears to be an even
      more attractive approach. Preliminary clinical studies have clearly demonstrated
      the ability of radioimmunoconjugates, especially when administered at high dose
      followed by bone marrow rescue, to induce durable complete remission in patients
      with non-Hodgkin's lymphomas refractory to conventional therapies.
      Radioimmunotherapy also overcomes the antigenic heterogeneity of the tumour cell
      population, since antigen negative tumour cells will be irradiated by the nearby
      targeted antigen-positive cells. Efforts should now be focused on defining more
      precisely the optimal clinical setting for administration of immunotoxin and
      radioimmunoconjugates (e.g. minimal residual disease), to reduce the
      immunogenicity of these compounds and solve the problem of vascular leak
      syndrome.

PMID- 9547999
TI  - Antisense therapy for B cell lymphomas.

PMID- 9548000
TI  - Gene therapy for B cell lymphomas.
AB  - The use of genes or genetically modified cells for therapeutic benefit is likely
      to have a significant therapeutic role for patients with B cell lymphomas in the
      future. To date, most gene therapy strategies applicable to the therapy of these
      diseases have not reached the point of clinical study. Adoptive immunotherapy
      using donor leucocyte infusion to treat aggressive B cell neoplasms in
      immunosuppressed patients has, however, shown great promise clinically, and
      studies of idiotypic vaccination in patients with low grade B cell neoplasms are
      also under way. Results from in vitro and animal studies continue to suggest that
      it may become possible to use the immune system for therapeutic benefit, and many
      current basic research strategies in the gene therapy of B cell non-Hodgkin's
      lymphoma are based on immune modulation of T cells or tumour cells themselves.
      Other major approaches to gene therapy for B cell malignancies include the
      introduction of directly toxic or "suicide genes" into B cells or the
      chemoprotection of haemopoietic stem cells by the introduction of drug resistance
      genes. All of these approaches require efficient and accurate gene transfer as
      well as correct expression of the gene product within the target cell. Although
      some way from therapeutic use, specific targeting of gene delivery is an area of
      active investigation and will be of value in many of the gene therapy strategies
      applicable to B cell lymphomas.

PMID- 9548002
TI  - Secondary prevention for stroke after CAPRIE and ESPS-2. Opinion 2.

PMID- 9548001
TI  - Secondary prevention for stroke after CAPRIE and ESPS-2. Opinion 1.

PMID- 9548003
TI  - Magnetic resonance angiography detection of four asymptomatic intracranial
      aneurysms.

PMID- 9548004
TI  - Comparison of the three strategies of verbal scoring of the Glasgow Coma Scale in
      patients with stroke.
AB  - Presence of aphasia in patients with stroke poses a problem in the use of the
      full form (eye-motor-verbal) Glasgow Coma Scale (GCS). Stroke investigators and
      clinicians have used three different strategies to deal with the untestable
      verbal subscale, i.e. eliminating the verbal subscale; pseudoscoring with 'one',
      and median value substitution; but the predictive accuracy of the strategies has
      not been compared. To compare the predictive accuracy of the three strategies for
      acute mortality in stroke, we prospectively applied the GCS to 275 consecutive
      patients with acute stroke and recorded their survival status before discharge
      from hospital. 95 (33.8%) patients died. 32 (12%) patients had untestable verbal
      score. Receiver-Operator-Characteristic curves for predicting mortality were
      constructed with the GCS sum score and with the multivariate logistic models, and
      areas under the curves were measured to compare the predictive accuracy. They
      were all found to be similar (0.87-0.88 sq unit). Specifically, the GCS with eye
      and motor subscale had 87% accuracy compared to 88% for the model with eye, motor
      and verbal scale. We conclude that the short-form (eye-motor) GCS is as good a
      predictor of early mortality (within 2 weeks) as the full form (eye-motor-verbal)
      GCS in patients with stroke.

PMID- 9548005
TI  - Stroke register: experience from the eastern province of Saudi Arabia.
AB  - A stroke registry was established in the Eastern Province of Saudi Arabia with an
      estimated population of 750,000 inhabitants of whom 545,000 are Saudi citizens.
      The register started in July 1989 and ended in July 1993. The Gulf war led to its
      interruption from August 1990 to August 1991. Four hundred eighty-eight cases
      (314 males, 174 females) of first-ever strokes affecting Saudi nationals were
      registered over the 3-year period. The crude incidence rate for first-ever
      strokes was 29.8/100,000/year (95% CI: 25.2-34.3/100,000 year). When standardized
      to the 1976 US population, it rose up to 125.8/100,000/year. Ischemic strokes
      (69%) predominated as in other studies but subarachnoid hemorrhage (SAH) was
      extremely rare (1.4%). The important risk factors were: systemic hypertension
      (38%), diabetes mellitus (37%), heart disease (27%), smoking (19%) and family
      history of stroke (14%). Previous transient ischemic attacks (3%) and carotid
      bruits (1%) were uncommon. The 30-day case fatality rate was 15%. The study
      showed that the age-adjusted stroke incidence rate for Saudis in this region is
      lower than the rates reported in developed countries but within the range
      reported worldwide. The pattern of stroke in Saudi Arabia is not different from
      that reported in other communities with the exception of the low incidence of
      SAH. The risk factors are similar to findings in other studies except for the
      high frequency of diabetes mellitus in our cases. The lower mortality rate was
      probably due to the younger age of the population and the availability of free
      medical services for management of cases.

PMID- 9548006
TI  - Impaired orientation in acute stroke: frequency, determinants, and time-course of
      recovery. The Copenhagen Stroke Study.
AB  - Orientation is an indicator of general intellectual function and is defined as
      the ability to report time, place, and personal data. Our knowledge of
      orientation in acute stroke is sparse. We examined the frequency of impaired
      orientation in acute stroke, its determinants, and recovery in 653 consecutive
      patients with acute stroke who were not unconscious and who were without severe
      aphasia. Prospective assessments of orientation and stroke severity were done by
      the Scandinavian Neurologic Stroke Scale at the time of acute admission and
      hereafter weekly until the end of rehabilitation. Impaired orientation was found
      in 23% of the patients on acute admission and in 12% of the survivors after
      completed rehabilitation. A stationary level of orientation was achieved by 80%
      of the patients within 2 weeks and by 95% within 6 weeks. A multiple linear
      regression analysis found neurological score (B = 0.027, SE(B) = 0.003), age (B =
      -0.013, SE(B) = 0.003), and comorbidity (B = -0.023, SE(B) = 0.078), but not sex,
      prior stroke, handedness, or side of stroke lesion to be significant independent
      determinants of orientation score on acute admission. Lesions involving the
      anterior and medial thalamus and/or any of the cerebral lobes were associated
      with impaired orientation. In conclusion, impaired orientation is frequent in
      acute stroke and the time-course of recovery is similar to what has been found in
      other neuropsychological impairments with the major part of recovery early after
      stroke onset.

PMID- 9548007
TI  - Cognitive alterations in non-demented CADASIL patients.
AB  - CADASIL is an inherited small-artery disease of the brain due to mutations of the
      Notch3 gene on chromosome 19. It is characterized by strokes, migraine with aura,
      and severe mood disturbances during mid adulthood and leads progressively to
      subcortical dementia. The precise onset of the cognitive decline in CADASIL
      remains unknown. We report here the cognitive evaluation of 8 non-demented
      symptomatic patients with CADASIL from 35 to 66 years of age. Altered
      performances were found in all subjects with the Wisconsin Card-Sorting Test
      (WCST), in 5/8 with the Trail-Making Test, and in 3/8 with copying of Rey's
      figure. Altered performances with codes and similarities of the WAIS-R, the
      Wechsler Memory Scale, Raven's Progressive Matrices, and the category and letter
      fluency task were observed less frequently (n < or = 2). The score obtained with
      the WCST was not significantly correlated with the severity of the white-matter
      or basal ganglia signal abnormalities at MRI examination. Our data show that: (1)
      symptomatic CADASIL patients, although non-demented, can present with a subtle
      cognitive impairment; (2) tasks involving the frontal lobes are found most
      frequently altered, and (3) this subtle cognitive deficit can develop in the
      absence of major vascular events and does not appear to be correlated with the
      severity of brain lesions as seen at MRI examination.

PMID- 9548008
TI  - Mitochondrial DNA in stroke and migraine with aura.
AB  - Patients presenting with thrombotic stroke of unexplained etiology and or
      migraine with aura were screened for mitochondrial (mt) DNA mutations associated
      with cytopathies given that both migraine and stroke-like episodes are recognised
      with certain mt DNA mutations. Mutations usually associated with either
      mitochondrial encephalopathy, lactic acidosis and stroke-like episode, myoclonic
      epilepsy with ragged red fibres, or those strongly linked to Leber's hereditary
      optic neuropathy (LHON) were not detected in patients or controls. However,
      increased levels of two of the secondary LHON mutations were found. The T-->C
      mutation at nucleotide 4216 was more common than expected in patients aged 35
      years or less, as was the 13708 G-->A mutation in young stroke patients. This
      data lends support to the possibility that an accumulation of minor mt DNA
      mutations may contribute to the pathoaetiology of stroke and migraine with aura
      in some young patients.

PMID- 9548009
TI  - Frequency and determinants of microembolic signals on transcranial Doppler in
      unselected patients with acute carotid territory ischemia. A prospective study.
AB  - BACKGROUND AND PURPOSE: Few data exist regarding to the occurrence of
      microembolic high-intensity transient signals (HITS) on transcranial Doppler
      ultrasound (TCD) in unselected acute stroke patients. The aim of this study was
      to investigate prospectively the frequency and determinants of HITS in acute
      carotid territory ischemia. We hypothesized that carotid artery disease, cardiac
      abnormalities, and nonlacunar infarcts were independent predictors of HITS in
      acute stroke. METHODS: We investigated 145 consecutive patients with acute
      internal carotid artery territory ischemia. The median time interval between
      stroke and TCD examination was 2 days. TCD monitoring was performed for 30 min on
      each middle cerebral artery. The frequency of HITS was cross-classified with
      carotid artery status, potential cardiac sources of embolism, and nonlacunar
      infarct subtype. Multivariate logistic regression models determined the
      independent relationship of these variables to HITS. RESULTS: Microembolic
      signals were detected in 35 patients (24.1%), Ipsilateral carotid artery disease
      was significantly and independently associated with HITS (odds ratio 3.3, 95%
      confidence interval 1.4-7.8, p = 0.007), whereas potential cardiac sources (OR
      1.07, 95% CI 0.48-2.4, p = 0.84) and infarct subtype (OR 0.84, 95% CI 0.29-2.4, p
      = 0.75) were not. CONCLUSIONS: High-intensity transient signals can be found in
      almost 25% of patients with acute anterior cerebral circulation ischemia and are
      significantly more prevalent among those with symptomatic carotid artery disease.
      Future clinical studies are required to determine whether HITS are a marker of
      increased stroke recurrence and can help to clarify stroke etiology in patients
      with competing stroke mechanisms.

PMID- 9548010
TI  - Venous Doppler ultrasound assessment of the parasellar region.
AB  - The purpose of this report is to present normal values for venous blood flow
      velocities from the parasellar region using transcranial Doppler ultrasound (2
      MHz transducer) with both transtemporal and transorbital approaches and to
      examine the nature of previously reported low-pulsatility signals with velocities
      in the arterial range from this area. Forty-three subjects ranging in age from 18
      to 56 years (mean +/- SD, 31.9 +/- 10.1 years) were examined. In all subjects, a
      venous signal directed away from the probe with the source lateral to the
      internal carotid artery siphon was detected on at least one side. A total of 72
      parasellar venous signals were insonated. Signals were considered to belong to
      the main inflow and outflow vessels of the cavernous sinus. The mean blood flow
      velocity ranged from 6 to 81 cm/s (mean +/- SD, 27.3 +/- 17.4 cm/s). Typical
      transients in the Valsalva test confirmed the venous character of the signals. No
      significant gender, side-to-side or age dependency was observed. A separate
      analysis was done for venous high-velocity signals defined by a mean blood flow
      velocity greater than 30 cm/s. They were detected in 21 out of 43 subjects
      (48.9%) via a transtemporal approach and in 6 of them (14%) via the transorbital
      route, too. Again, no significant gender, side-to-side or age dependency was
      noted. In summary, we found a greater variability of venous blood flow velocities
      in the parasellar region compared to other basal cerebral veins, e.g. the basal
      vein of Rosenthal. The previously reported low-pulsatility signals with
      velocities in the arterial range proved to be of venous origin.

PMID- 9548012
TI  - Complications of acute ischaemic stroke.
AB  - Neurological, cardiac, and systemic complications during the first days to weeks
      after ischaemic stroke can cause substantial morbidity and mortality. The
      reported 30-day case fatality rate for cerebral infarction varies between 10 and
      17%. The incidence and effects of the various complications vary with time after
      stroke: transtentorial herniation and other cerebral complications prevail during
      the 1st week, whereas medical complications are more prominent in the weeks
      thereafter. Many complications are treatable, and some are preventable. The goal
      of this report is to provide information on their incidence, consequences, and
      management.

PMID- 9548011
TI  - Autonomic nervous activity during sleep in middle cerebral artery infarction.
AB  - No data are available on the autonomic system during sleep in patients with
      stroke. The purpose of this study was to determine the influence of acute
      ischemic stroke on the autonomic cardiovascular system during sleep, and to
      correlate autonomic activity with the clinical status of patients. Ten patients
      with ischemic stroke in the middle cerebral artery were studied by means of an
      all-night polysomnographic recording within the 1st week of the onset of symptoms
      and at the 3-week follow-up examination. Power spectrum analysis of the heart
      rate variability was performed using an autoregressive algorithm in 180
      consecutive electrocardiographic RR intervals. Spectral power was calculated in 3
      main frequency bands: high frequency (HF), 0.15-0.4 Hz; low frequency (LF), 0.04
      0.15 Hz; very low frequency (VLF), < 0.04 Hz. The data were compared with those
      of 10 age-matched controls. A significant increase in VLF (p < 0.0005) and a
      decrease in HF (p < 0.0002) components were found in ischemic stroke patients.
      The sympathetic-parasympathetic balance (VLF + LF/HF) was higher in patients than
      controls (p < 0.005). However, these components changed significantly during
      sleep, revealing a physiological pattern. These power spectral data were still
      present at the 3-week follow-up. The 4 patients who developed cardiac arrhythmias
      showed higher sympathetic-parasympathetic balance than patients without
      arrhythmias (p < 0.05). These data suggest a sympathetic predominance in patients
      with acute ischemic stroke during sleep. However, the flexible and dynamic
      properties of the autonomic nervous system are preserved. Cardiac arrhythmias
      following stroke may be related to the degree of sympathetic predominance.

PMID- 9548013
TI  - Detection of intraluminal thrombus in acute stroke by proton density MR imaging.

PMID- 9548014
TI  - Hormone replacement therapy in gynecological cancer survivors.

PMID- 9548015
TI  - Surgery or radiation: is there really a choice for early prostate cancer.
AB  - One of the most difficult tasks for the practicing urologist is to counsel the
      patient in a decision for the optimal treatment for his localized prostate
      cancer. After providing the patient with contemporary and unbiased information
      and data, it is important to find the preferred treatment based on his age, the
      medical realities and, last but not least, the patient's personal preference.
      Radical prostatectomy, radiotherapy and observation are standard treatment
      options. TRUS-guided brachytherapy and cryosurgery are considered investigational
      treatment options since follow-up is inadequate to provide sufficiently precise
      outcome estimates. The literature does not provide clear-cut evidence for the
      superiority of any one treatment. The patient most likely to benefit from radical
      prostatectomy would have a relatively long life expectancy, no significant
      surgical risk factors and a preference to undergo surgery. The major advantage of
      radical prostatectomy is its potential for total removal of the cancer and cure
      in properly selected patients. Potential harm includes urinary incontinence and
      impotence. The patient most likely to benefit from radiation therapy would have a
      relatively long life expectancy, no significant risk factors for radiation
      toxicity and a preference for radiotherapy. The advantages of radiotherapy are
      that it has a potential for cure and it is well tolerated in the majority of men
      when the modern techniques are used. Potential harm includes radiation cystitis,
      proctitis and impotence, persisting severe complications are only seen in 1% of
      patients. The patient most likely to benefit from surveillance are those with a
      shorter life expectancy and/or a low grade tumour. Benefits are lack of treatment
      related morbidity with only marginal compromise of disease-specific survival at 5
      10 years follow-up.

PMID- 9548016
TI  - The cellular biology of B-cell chronic lymphocytic leukemia.
AB  - In conclusion, B-CLL cells through their immunophenotype have the functional
      potential required to interact with cells in what has been called the
      immunological synapse, i.e. the cognate interactions between T-cells, antigen
      presenting cells and B-cells during immunopoiesis. The data reviewed herein
      provides substantial evidence to suggest that B-CLL cells in fact can interact,
      not only with T-cells but also with endothelial cells and stromal cells in the
      bone marrow. These interactions, in particular signaling through CD40, contribute
      to extended survival and proliferation of B-CLL cells and, thereby, the risk of
      complete malignant transformation of the clone. Therefore, this review would
      suggest that the answers to how B-CLL is initiated may be found in molecules
      responsible for the normal regulation of immunopoiesis. Transformation to
      malignancy, by contrast, is likely to be caused by loss of control over the G1
      restriction in the cell cycle in B-CLL cells.

PMID- 9548018
TI  - Cytoskeletal and adhesion protein changes during neoplastic progression of human
      prostate epithelial cells.

PMID- 9548017
TI  - Anthracycline-induced cardiotoxicity in children and young adults.

PMID- 9548019
TI  - Violence faced by staff in a learning disability service.
AB  - This study explores the issue of violence experienced by staff in the learning
      disability service of an NHS Trust. Based on the literature review a
      questionnaire survey was sent to all staff employed in the Trust's learning
      disability service (n = 295). The questionnaire sought: background details of
      respondents; numerical incidences and types of violence experienced over the
      previous 12 months; reporting mechanisms; reactions to and impact of violence on
      individuals and their work; support received. Vignettes provide a rich picture of
      the types of violent incidences and their impact. The findings show that 81% of
      staff in the learning disability service had experienced violence in the previous
      12 months. Many had numerous experiences of violence. New and inexperienced staff
      are particularly vulnerable. Training and support systems are, on the whole,
      limited. Support received from colleagues is generally regarded as more helpful
      than that of line management. To explore good practice elsewhere, semi-structured
      interviews were held with individuals working with potentially violent clients in
      organizations other than the learning disability service. Suggestions are offered
      for putting in place human resource strategies to reduce the incidences of
      violence and provide appropriate post-incident support for staff on a continuing
      basis.

PMID- 9548020
TI  - Knowledge of stroke in rehabilitation and community samples.
AB  - This study examined the stroke knowledge of 60 stroke rehabilitation patients, 46
      spouses, 25 family members, and 103 people in the general community. Changes in
      stroke knowledge with time, and determinants of stroke knowledge, were also
      examined. Clinical participants were assessed on acute admission, admission to
      and discharge from rehabilitation, and 6 and 12 months after discharge. Community
      participants were assessed once. Instruments used were the Stroke Care
      Information Test, Australian ADL Index, Frenchay Activities Index, Illness
      Behaviour Questionnaire and Zung Self-rating Depression Scale. The stroke
      knowledge of all participants, particularly patients, was poor, but improved with
      time. Better-informed patients were younger, had milder strokes, were less
      depressed, were less likely to develop abnormal illness behaviour, and made a
      better functional recovery than patients with poorer knowledge. Structured
      information programmes are needed for stroke patients and their families.
      Improved community awareness of stroke may help the prospects for recovery and
      quality of life for people who have strokes.

PMID- 9548021
TI  - Is neurological rehabilitation ready for 'immersion' in the world of virtual
      reality?

PMID- 9548022
TI  - Does virtual reality have a place in the rehabilitation world?

PMID- 9548023
TI  - Virtual reality: a fascinating tool for motor rehabilitation (to be used with
      caution)

PMID- 9548024
TI  - Virtual reality: opening the way.

PMID- 9548025
TI  - Virtual reality: consumer perspectives.
AB  - This commentary extends the discussion of the applications of virtual reality to
      persons with disabilities by focusing on: (a) the use of virtual reality for
      stimulating residential features for persons being deinstitutionalized into four
      person community residences; and (b) the involvement of consumers in key
      decisions regarding their residence and personal assistive technologies.

PMID- 9548026
TI  - Virtual reality in rehabilitation.

PMID- 9548027
TI  - A rejoinder.

PMID- 9548028
TI  - Sports-medical assessment for athletes with a disability.
AB  - The purpose of this article is to describe a Sports-Medical Assessment Protocol
      (SMAP) for athletes with a disability. The purposes of the SMAP are to identify
      medical problems and therapeutic goals for supplementary training programmes for
      athletes with a disability, and to provide baseline data for future follow up.
      The SMAP includes an interview, cardiorespiratory assessment and physical and
      functional examination. Data were collected from assessment protocols of 14 male
      athletes with various neurological disorders who qualified to participate in the
      Atlanta Paralympic Games in 1996. Nine of the athletes had some range of motion
      (ROM) limitations, one had shoulder pain and one low back pain following physical
      stress. Two athletes with postpolio presented muscle fasciculation and one of
      them also presented bilateral Carpal Tunnel Syndrome. Based on the results we
      concluded that utilizing the SMAP may contribute to trainers' and athletes' (with
      a disability) awareness of the physical needs of elite athletes as well as
      participants in leisure sport activities.

PMID- 9548029
TI  - Developmental patterns of heart rate and variability in infants with persistent
      apnea of infancy.
AB  - During periods of regular breathing, heart rate is slower and more variable in
      healthy (no history of respiratory distress syndrome) prematurely born infants
      with persistent apnea, relative to full-term control infants of comparable post
      conceptional ages. We tested the hypothesis that the cardiovascular differences
      may be linked to the persistent apnea, rather than premature birth, by assessing
      heart rate and variability in full-term infants with persistent apnea. Thus,
      resting heart rate and variability were compared in full-term infants with apnea
      of infancy, prematurely born infants with persistent apnea, and full-term control
      infants. Full-term infants with persisting apnea showed slower heart rates than
      control infants, beginning at 4 months after birth, and enhanced heart rate
      variability beginning at 6 months. Healthy prematurely born infants with
      persistent apnea showed cardiovascular alterations similar to those of full-term
      infants with apnea; these alterations differed from those observed in very
      premature infants with histories of respiratory distress. The postnatal
      development of cardiovascular aberrations in infants with persistent apnea
      suggests that mechanisms accompanying apneic events may contribute to long-term
      alterations in autonomic control.

PMID- 9548030
TI  - Hourly fetal urine production rate in the near-term fetus: is it really increased
      during fetal quiet sleep?
AB  - Fetal bladder volume and hourly fetal urine production (HFUPR) is calculated on
      the assumption that the fetal bladder is ellipsoid in shape. A recent validation
      study demonstrated a progressive overestimation at increasing bladder volumes.
      This may be due to changes in shape of the fetal bladder at increasing volumes.
      Two independent papers have shown increased HFUPR during fetal behavioural state
      1F (S1F) when compared with S2F. The aim of the present study was to assess
      whether this increase of HFUPR during S1F, previously observed by others, could
      be the result of an error introduced by the method of volume calculation. A
      retrospective evaluation was performed in a series of 208 HFUPR measurements in
      123 normal near term pregnant women attending a low-risk atenatal clinic.
      Adequate bladder filling in both states was identified in 43 recordings. Maximum
      fetal bladder volumes were greater (> 10 ml) during S1F in comparison to S2F in
      56% of these recordings and HFUPR was significantly greater during S1F only in
      these cases. Bladder volumes are usually lower during S2F as a result of fetal
      voiding, which occurred in association with 22 of 36 transitions from S1F to S2F,
      and only 1 of 13 transitions from S2F to S1F (P < 0.001). When disregarding
      calculated bladder volumes in excess of 20 ml for the purpose of calculating
      HFUPR, eleven recordings remained. HFUPR calculated in this way was significantly
      lower in comparison to measurements where larger bladder volumes were included
      and no difference was observed between states. This implies that the differences
      observed are the result of the greater error in calculating bladder volumes and
      HFUPR during S1F, where volumes are usually greater and that calculation of fetal
      bladder volume should not be performed on the assumption that the bladder is
      ellipsoid in shape. Alternative techniques include limiting measurements to a
      maximum volume of approximately 20 ml, when the bladder is usually ellipsoid in
      shape or basing volume calculation on the surface area of a series of sagittal
      views as suggested by Hedriana and Moore [Hedriana HL, Moore TR. Ultrasonographic
      evaluation of human fetal urinary flow rate: accuracy of bladder volume
      estimations. Am J Obstet Gynecol 1994;170:1250-1254; Hedriana HL, Moore TR.
      Accuracy limits of ultrasonographic estimation of fetal urinary flow rate.

PMID- 9548031
TI  - Cardiovascular responses to feeding in the neonate during the first four days of
      life.
AB  - Prior work has demonstrated acute cardiovascular responses associated with breast
      and bottle feeding of newborn infants that consist of increases in both blood
      pressure and heart rate. This current study sought to determine if the amplitude
      of these responses is related to the age of the infant and/or the amount of
      nutrient ingested during the study period. Results show that the magnitude of the
      feeding responses does not change over the first four days of life. In a second
      study it was found that changes in systolic blood pressure during feeding are
      positively correlated with volume of nutrient intake during the initial phase of
      feeding (r = +0.75, p < 0.01). These results suggest that some of the individual
      variability in the increase in blood pressure during feeding is related to the
      amount of nutrient ingested. It is not known whether these differences are due to
      differences in sucking effort or other aspects of feeding efficiency.

PMID- 9548032
TI  - Neurological condition in 42-month-old children in relation to pre- and postnatal
      exposure to polychlorinated biphenyls and dioxins.
AB  - Adverse neurological effects of exposure to PCBs have been found up to 18 months
      of age. Now we report on the effect of pre- and postnatal exposure to PCBs and
      dioxins on the neurological condition at 42 months of age. For this purpose, PCB
      levels were determined in cord and maternal plasma, and used as a measure of
      prenatal exposure. Breast milk was analyzed for PCBs and dioxins. In addition,
      PCBs were determined in plasma sampled from the child at 42 months of age. We
      evaluated the neurological condition of 394 children using the Touwen/Hempel
      method. After adjustment for covariates, neither prenatal PCB exposure nor
      postnatal exposure to PCBs and dioxins was found to be related to the
      neurological condition at 42 months of age.

PMID- 9548033
TI  - Maternal nutritional status, diabetes and risk of macrosomia among Native
      Canadian women.
AB  - Multivariate methods were used to identify risk factors for macrosomia (birth
      weight > 4000 g) among 741 singleton births to Native Canadian women from Sioux
      Lookout Zone, Ontario, Canada, in 1990-1993. The average birth weight was 3691 +/
      577 g, and 29.2% of infants weighed more than 4000 g at birth. Macrosomic
      infants were born at later gestational ages and were more likely to be male.
      Women delivering macrosomic infants were taller, entered pregnancy with higher
      body mass indexes (BMI) and gained more weight during pregnancy, but were less
      likely to smoke cigarettes. They were more likely to have previously delivered a
      macrosomic infant and to have had gestational diabetes mellitus (GDM). Risk of
      macrosomia was associated with maternal glycemic status; women with pre-existing
      diabetes were at greatest risk, followed by those with GDM A2 (fasting glucose >
      or = 6 mmol/l). Women with GDM A1 (fasting glucose < 6 mmol/l) were not at
      increased risk for delivering a macrosomic infant, but glucose-tolerant women
      with high glucose concentrations 1 h after the 50 g challenge were at somewhat
      increased risk. Maternal glycemic status and maternal nutritional status before
      and during pregnancy are important determinants of macrosomia in this native
      population.

PMID- 9548034
TI  - Screening for inborn errors of metabolism in high-risk children from Rio de
      Janeiro, Brazil.
AB  - From 1988 to 1995, our laboratory at the Institute of Chemistry of the Federal
      University of Rio de Janeiro, in Rio de Janeiro, screened 2650 samples from 2000
      high-risk patients (mostly children) for Inborn Errors of Metabolism (IEM).
      Chemical tests, various chromatographic techniques and enzyme assays were
      performed on urine, plasma and in some cases, cerebrospinal fluid (CSF). A total
      of 145 cases of IEM (7.2%) was identified. These were related to: the metabolism
      of amino acids (41) and carbohydrates (17), organic acids (7), lysosomal enzymes
      (61), membrane transport system (16), metals (2), intestinal disaccharidases (1)
      and porphyrin metabolism (3). Furthermore, a relevant number of patients with
      abnormal findings is still under investigation. Biochemical results and clinical
      symptoms are presented and the importance of reference laboratories for the
      detection of IEM is stressed.

PMID- 9548035
TI  - Laparoscopy as a day-case procedure in patients with liver disease.
AB  - BACKGROUND AND STUDY AIMS: The present study was aimed at exploring the
      feasibility of diagnostic laparoscopy on a day-case basis in patients with liver
      disease. PATIENTS AND METHODS: Retrospective analysis was carried out of 85
      consecutive day-case laparoscopies performed between January 1990 and January
      1994. During this period, patients were observed in day-care facilities for a
      period of three hours. Patients' perception and acceptance of the procedure were
      assessed using a postal questionnaire. RESULTS: Laparoscopy was successful in 84
      of the 85 patients; adequate liver biopsies were obtained in 83 patients. In
      three cases, the procedure was converted to a one-night hospital admission
      because of pain (1), persistent sedation (1) and collapse (1). Abdominal skin
      hematomas were reported by eight patients, and fever by two. Serious
      complications were not observed. The majority of patients experienced no
      complaints, or minor ones, after the procedure, and they expressed a preference
      for an outpatient procedure in case a renewed investigation might be indicated.
      Compared with in-hospital procedures, day-case laparoscopy was associated with a
      33% reduction in cost. CONCLUSIONS: Diagnostic laparoscopy, with the hospital
      stay reduced to three hours, can be performed safely as a day-case procedure in
      selected patients.

PMID- 9548036
TI  - Does laparoscopic cardiomyotomy require an antireflux procedure?
AB  - BACKGROUND AND STUDY AIMS: There is controversy concerning the need for an
      antireflux procedure in patients undergoing open or endoscopic cardiomyotomy for
      achalasia. The addition of an antireflux wrap (partial or total), while
      preventing reflux, may result in persistence or incomplete relief of dysphagia in
      patients with total oesophageal aperistalsis. The technique of laparoscopic
      cardiomyotomy used in Dundee preserves the lateral and posterior attachments of
      the gastro-oesophageal junction, and was designed to minimize the risk of gastro
      oesophageal reflux. PATIENTS AND METHODS: A consecutive series of patients with
      achalasia (n = 19) were treated by laparoscopic cardiomyotomy using the Dundee
      technique, which limits the mobilization to the anterior wall of the abdominal
      and thoracic oesophagus. The patients were followed up prospectively to assess
      the long-term relief of dysphagia and the postoperative incidence of reflux
      symptoms, with or without oesophagitis. RESULTS: The follow-up symptoms and
      assessment of the patients (15-53 months, median 27 months) showed total relief
      (n = 12) or substantial relief (n = 5) of dysphagia in 89%. On assessment at a
      median follow-up of 27 months, the number of patients experiencing heartburn
      after this operation increased from four of 15 to five of 15, and one patient
      (6.6%) developed endoscopically proved oesophagitis, with a positive oesophageal
      pH monitoring test. CONCLUSIONS: The routine addition of an antireflux operation
      is not justified in patients undergoing laparoscopic cardiomyotomy, provided that
      the lateral and posterior attachment of the oesophagus are kept intact.

PMID- 9548038
TI  - The role of surveillance endoscopic retrograde cholangiopancreatography in
      preventing episodic cholangitis in patients with recurrent common bile duct
      stones.
AB  - BACKGROUND AND STUDY AIMS: Approximately 2-7% of patients who have undergone
      previous removal of bile duct stones have recurrence often presenting as
      ascending cholangitis. The aim of this study was to identify the incidence,
      clinical presentation, and objective findings in this group of patients.
      Additionally, the effect of surveillance endoscopic retrograde
      cholangiopancreatography (ERCP) in preventing cholangitis, was studied. PATIENTS
      AND METHODS: Two thousand and ninety-six patients who underwent ERCP for
      cholelithiasis were studied with 45 of these patients being identified as having
      recurrent common bile duct stones. Of the 45, 13 had two or more recurrences
      without having any obvious predisposing factors. The mean age of the 13 patients
      was 57 years. The characteristics of 13 patients were reviewed, including
      sphincterotomy size, liver function tests, and contrast drainage time. RESULTS:
      All 13 patients with recurrent stones presented with ascending cholangitis.
      Stones were found to be soft, brown and accompanied by a large amount of sludge.
      The common bile duct in all 13 patients was noted to be dilated and had notable,
      widely patent sphincterotomes. There was significant delayed drainage in 77% of
      these patients. Yearly surveillance ERCPs were performed in the 13 patients, the
      incidence of acute cholangitis episodes per patient decreased from 2 to 0.6 with
      a four-year follow-up. CONCLUSION: In a subgroup of patients with multiple common
      bile duct stone recurrences, annual surveillance ERCP with stone removal
      decreases the incidence of recurrent episodes of ascending cholangitis as well as
      its associated morbidity and mortality.

PMID- 9548037
TI  - Endoscopic papillary balloon dilation for the management of common bile duct
      stones: experience of 226 cases.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy is a widely accepted
      technique for the treatment of patients with common bile duct stones. However, it
      is still associated with occasional complications. The recently developed
      technique of endoscopic papillary balloon dilation seems to be a safe and
      effective procedure, and to have great potential for replacing endoscopic
      sphincterotomy. However, few reports have been published on the use of this
      technique for bile duct stones. The present study was undertaken to evaluate its
      safety and efficacy. PATIENTS AND METHODS: Endoscopic papillary balloon dilation
      was used to remove common bile duct stones in 226 consecutive patients including
      41 patients of ASA classification III/IV, 41 elderly patients (> 80 years) 24
      with liver cirrhosis, and 86 with periampullary diverticulum. After dilation of
      the papilla with a balloon diameter of 8 mm, the stones were retrieved. RESULTS:
      In conjunction with the use of a mechanical or/and electrohydraulic lithotriptor
      in 79 patients (35%) with large stones (> 10 mm in diameter), clearance of the
      common bile duct was achieved in 225 of 226 patients (99%) without serious
      complications, such as hemorrhage or severe pancreatitis; mild (n = 13) or
      moderate (n = 2) pancreatitis occurred in 7% of cases. CONCLUSIONS: Endoscopic
      papillary balloon dilation is a safe and effective technique for the treatment of
      common bile duct stones, even in high-risk patients.

PMID- 9548039
TI  - A prospective, randomized controlled trial of sedation vs. no sedation in
      outpatient diagnostic upper gastrointestinal endoscopy.
AB  - BACKGROUND AND STUDY AIMS: The majority of gastrointestinal endoscopists in the
      United Kingdom routinely use intravenous sedation prior to diagnostic upper
      gastrointestinal endoscopy. We conducted a prospective, randomized controlled
      clinical trial to help determine whether the use of sedation influences the
      duration, safety, and tolerance of diagnostic upper gastrointestinal endoscopy.
      PATIENTS AND METHODS: Adults referred for outpatient diagnostic upper
      gastrointestinal endoscopy were invited to participate in the study. Patients
      with a history of previous upper gastrointestinal endoscopy or dysphagia were
      excluded. Patients were prospectively randomized to sedation with intravenous
      midazolam (5 mg for those under 65 years or 3 mg for those aged 65 or more), or
      no sedation. All patients were given topical oropharyngeal anaesthesia with 100
      mg lignocaine spray. Outcome measures included duration of procedure, ease of
      procedure (as assessed by medical and nursing staff), tolerance of procedure (as
      assessed by patients), and incidence of complications. RESULTS: 100 patients were
      randomized to receive sedation or no sedation. The two groups were well matched
      for age, sex, and number of biopsies taken during the procedure. In the non
      sedated group, the duration of endoscopy tended to be reduced and the procedure
      tended to be easier according to the endoscopists' assessment (neither of these
      observations was significant). The sedated group reported greater comfort for the
      procedure (P < 0.001), although both groups tolerated the procedure well, and the
      majority in both groups preferred to have any future procedure repeated in the
      same manner. There were no serious adverse events in either group. CONCLUSIONS:
      In patients who are willing to contemplate upper gastrointestinal endoscopy
      without sedation, the avoidance of sedation may lead to faster and easier
      endoscopies, without any increased risk of procedural difficulties or adverse
      events.

PMID- 9548040
TI  - Effect of large fundal varices on changes in gastric mucosal hemodynamics after
      endoscopic variceal ligation.
AB  - BACKGROUNDS AND STUDY AIMS: Effect of endoscopic variceal ligation (EVL) on
      gastric mucosal hemodynamics would differ in patients with and without large
      fundal varices. The aim of this study was to test this hypothesis. PATIENTS AND
      METHODS: Twenty-seven patients with cirrhosis and large sized esophageal varices
      were prospectively studied. There were eight patients with large fundal varices
      and 19 patients without large fundal varices. Before EVL, gastric mucosal
      hemodynamics were endoscopically assessed by laser-Doppler velocimetry and
      reflectance spectrophotometry in the antrum and the corpus. In the reflectance
      spectrophotometric measurements, gastric mucosal hemoglobin content (IHb) and
      gastric mucosal oxygen saturation (ISO2) were determined. The severity of portal
      hypertensive gastropathy (PHG) was also recorded at the antrum and the corpus.
      For data analysis, PHG was scored (absent, 0; mild, 1; severe, 2; bleeding, 3).
      These measurements were repeated after initial (three days after initial session)
      and repeated (seven days after last session) EVL. RESULTS: At the antrum, neither
      PHG score nor gastric mucosal hemodynamic parameters were modified after initial
      and repeated EVL in patients with and without large fundal varices. In addition,
      no significant differences of the integrated changes in PHG score and gastric
      mucosal hemodynamic parameters were observed in the two groups. At the corpus,
      PHG score significantly increased after initial and repeated EVL in patients
      without large fundal varices. In these patients, laser-Doppler signal and ISO2
      significantly decreased and IHb significantly increased after initial and
      repeated EVL. In contrast, PHG score, laser-Doppler signal, and ISO2 did not
      change significantly in patients with large fundal varices, although IHb
      transiently increased after initial EVL. Furthermore, the integrated changes in
      PHG score and gastric mucosal hemodynamic parameters were significantly lower in
      patients with large fundal varices than in those without. CONCLUSION: The
      aggravation of PHG after EVL is due to congestion of the gastric mucosal
      circulation. The presence of large fundal varices plays a protective role in the
      development of EVL-induced gastric mucosal hemodynamic derangement.

PMID- 9548041
TI  - Endosonography-guided biopsy of mediastinal and pancreatic tumors.
AB  - BACKGROUND: Although endoscopic ultrasound (EUS) allows sensitive imaging of the
      upper gastrointestinal (GI) tract, it remains difficult to differentiate between
      benign and malignant lesions on the basis of ultrasound morphology. The purpose
      of this study was to determine the value of EUS-guided biopsy for the diagnosis
      of submucosal and extraluminal tumors. METHODS: EUS-guided biopsy was carried out
      in 50 patients with upper GI-tract lesions. All patients were examined using a
      flexible echoendoscope with a 5/7.5 MHz curved array transducer. A specially
      designed biopsy device (type Vilmann) with a fine needle (diameter 0.8 mm) was
      used for EUS-guided biopsy. RESULTS: EUS-guided biopsy was performed for
      evaluation of mediastinal lesions (n = 15), pancreatic tumors (n = 26) and
      submucosal (n = 5) or stenotic tumors of the esophagus (n = 4). Fine-needle
      aspiration yielded diagnostic tissue samples in 44 of 50 patients (88%).
      Histology demonstrated benign lesions in 20 of 44 patients and malignant tumors
      in the other 24 patients. EUS-guided biopsy failed in only six patients (12%): in
      four patients it was impossible to advance the needle into very hard pancreatic
      tumors; non-representative biopsy material was obtained in two further cases. The
      results of EUS-guided biopsy were validated by surgery (n = 21), autopsy (n = 3)
      or clinical follow-up (n = 20). After a mean follow-up of 16 months there is no
      evidence of malignancy in any of the patients with benign histology. The
      sensitivity and specificity of EUS-guided biopsy in the diagnosis of malignancy
      were 88% and 100%, respectively. None of the patients experienced complications
      related to endosonographic biopsy. CONCLUSIONS: EUS-guided biopsy with the
      Vilmann needle device is a safe and accurate method for tissue sampling of
      extraluminal lesions. This technique considerably improves the diagnostic value
      of endosonography.

PMID- 9548042
TI  - Injection treatment of hemorrhage induced by endoscopic sphincterotomy.
AB  - BACKGROUND AND STUDY AIMS: Hemorrhage is one of the most common severe
      complications after endoscopic sphincterotomy (ES) and the mortality after
      surgical treatment can be as high as 50%. We prospectively evaluated the effect
      of injection treatment in nine patients with appreciable hemorrhage after ES.
      PATIENTS AND METHODS: Bleeding was detected immediately after ES in five patients
      and 48, 72, 120 and 216 hours after the procedure in the remaining four. Patients
      were treated with a combined injection of epinephrine and polidocanol (1-3 and 3
      6 ml, respectively) into the bleeding site. RESULTS: Treatment was effective in
      arresting hemorrhage in all cases. Two patients had abnormal clotting tests,
      which emphasizes the importance of identifying risk factors for hemorrhage before
      ES. No patient required operation and there were no late complications related to
      the injection during a mean follow-up period of six months. CONCLUSIONS: Our
      results suggest that bleeding after sphincterotomy can be safely and effectively
      controlled by a combined epinephrine and polidocanol injection, thereby avoiding
      operation.

PMID- 9548043
TI  - What to do when the papilla bleeds after endoscopic sphincterotomy.

PMID- 9548044
TI  - What is the current status of endoscopic balloon dilation for stone removal?

PMID- 9548045
TI  - The treatment of cricopharyngeal dysmotility with a transmucosal cricopharyngeal
      myotomy using the potassium-titanyl-phosphate (KTP) laser.
AB  - Cricopharyngeal dysfunction is a relatively uncommon disorder that is
      misunderstood by many physicians. Cricopharyngeal dysmotility is thought to
      indicate abnormal function in the upper esophageal or cricopharyngeal sphincter,
      the etiology of which is related to uncoordinated pharyngeal swallowing,
      achalasia, or a combination of these factors. Unfortunately, standard diagnostic
      tests do not consistently show that the cricopharyngeal sphincter malfunctions;
      so cricopharyngeal myotomy has been suggested as a diagnostic and therapeutic
      tool in the treatment of dysmotility. The current report reviews trends in the
      diagnosis and treatment of cricopharyngeal myotomy, including the results of
      cricopharyngeal myotomy using the potassium-titanyl-phosphate (KTP) laser. A
      transmucosal cricopharyngeal myotomy with the KTP laser may be a viable
      alternative for patients with cricopharyngeal dysmotility compared with
      conventional techniques.

PMID- 9548046
TI  - Forward-viewing endoscope or side-viewing duodenoscope for ERCP in patients after
      Billroth II gastrectomy?

PMID- 9548048
TI  - Early gastric cancer in a fundic diverticulum.

PMID- 9548047
TI  - Percutaneous endoscopic gastrostomy/jejunostomy in the early postoperative
      period.

PMID- 9548049
TI  - Esophageal perforation due to endoscopic retrograde cholangiopancreatography.

PMID- 9548050
TI  - Use of a new mouthpiece in placing a nasobiliary drainage tube.

PMID- 9548051
TI  - Biliary opening anomalies: ectopic drainage of pancreaticobiliary ducts.

PMID- 9548052
TI  - Application of clips during ERCP: a new anchoring method for redundant
      Kerckring's fold covering the duodenal papilla.

PMID- 9548053
TI  - Removal of Ascaris lumbricoides from the bile duct using balloon
      sphincteroplasty.

PMID- 9548054
TI  - Diagnostic endoscopic ultrasound of the pancreas may cause acute pancreatitis.

PMID- 9548055
TI  - Cocaine-induced ischemic colitis.

PMID- 9548056
TI  - Gastrointestinal involvement in infections caused by varicella virus.

PMID- 9548057
TI  - The Healthy Neighborhoods Project: a local health department's role in catalyzing
      community development.
AB  - Studies show that community development approaches to health education may lead
      not only to improved social, economic, and health status but also to increased
      individual participation in health education and preventive health care
      activities. However, because of categorical funding restraints and philosophical
      issues, local health departments have rarely given control of defining project
      outcomes to the community. One such project was in a low-income urban
      neighborhood in the San Francisco Bay Area. In this Healthy Neighborhoods
      Project, the health department catalyzed community development and organization
      in a multiethnic public housing complex. As a result, an empowered community
      successfully advocated to improve public safety by installing street speed humps
      and increased street lighting. After project completion, residents initiated
      several additional health actions, including the removal of a neighborhood
      tobacco billboard. This article describes the project, which may serve as a model
      for other urban public health programs to explore their role in community
      empowerment.

PMID- 9548059
TI  - Youth violence in the city: the role of educational interventions.
AB  - Interpersonal violence is a major cause of ill health in urban communities and a
      significant social and political problem. The epidemiology of interpersonal
      violence is summarized, highlighting the fact the youth are overrepresented as
      victims and perpetrators of violence. General areas of agreement and disagreement
      about programmatic approaches to reducing youth violence are summarized,
      emphasizing that the most effective programs are comprehensive and integrated and
      incorporate multiple strategies at multiple levels in multiple settings. Four
      types of educational strategies to reduce youth violence are summarized: conflict
      management skills training, youth-operated programs, psychoeducational
      strategies, and family-based educational strategies. Exemplars of each are
      presented, and their strengths and weaknesses are discussed. Strategies to
      implement effective programs are summarized, and the policy and program planning
      implications of what is known are discussed.

PMID- 9548058
TI  - Breaking the cycle of violence among youth living in metropolitan Atlanta: a case
      history of kids alive and loved.
AB  - More teenagers in the United States die from gunshot wounds than from all natural
      causes of disease combined. Firearm-related mortality accounts for almost half of
      all deaths among African American teens. Residents of central cities have the
      highest probability of experiencing violent crimes. This article describes an
      innovative community-based intervention designed to break the cycle of violence
      among youth in metropolitan Atlanta. The intervention, Kids Alive and Loved
      (KAL), emerged from the African American community as one mother's response to
      the violent death of her 17-year-old son. The authors describe how her response
      to tragedy gave birth to a culturally appropriate intervention for youth exposed
      to violence. This article delineates the evolution of KAL, the role of community
      partners in the design of the intervention, and how diffusion of innovation
      theory has implications for understanding the KAL approach to breaking the cycle
      of violence.

PMID- 9548060
TI  - Preventing Halloween arson in an urban setting: a model for multisectoral
      planning and community participation.
AB  - Arson is a violent crime and a public health problem that causes injuries and
      deaths, destroys homes, and destabilizes neighborhoods. During the late 1970s,
      pre-Halloween pranks in Detroit, Michigan, turned destructive when hundreds of
      fires were set deliberately throughout the city; in 1984, a record of 810 fires
      were set during the Halloween period. In 1985, a city wide anti-arson campaign
      that involved the mobilization and training of thousands of community volunteers
      was begun in Detroit. This report describes the multiple components of the anti
      arson intervention from 1985 through 1996 and changes in the incidence of
      Halloween fires. Both the decrease in annual Halloween arson fires after the
      intervention began and the inverse relationship between the number of volunteers
      and the number of fires suggest a causal effect. This study illustrates the
      capacity of an urban community to mobilize its residents and stakeholders, the
      importance of community participation and multisectoral partnerships in program
      planning and implementation, and the challenges faced in retrospectively
      evaluating an apparently successful, complex, community-based intervention.

PMID- 9548061
TI  - CINCH: an urban coalition for empowerment and action. Consortium for the
      Immunization of Norfolk's Children.
AB  - CINCH (Consortium for the Immunization of Norfolk's Children) is an urban
      coalition that was developed in 1993 to improve childhood immunization rates in
      Norfolk, Virginia. CINCH involves diverse citizens and institutions in effective
      community-based assessment, planning, and action. A needs assessment from 1993
      found that only 49% of Norfolk 2-year-olds were adequately immunized. Using this
      data, CINCH developed a plan focused on education and communication, support for
      at-risk families, increased access to immunizations, and improved immunization
      delivery. After federal funding ended in 1995, members voted to expand the scope
      of the coalition to address additional child health needs and to broaden the
      membership. CINCH is a model for a sustainable city-citizen learning environment
      that intervenes to "help families help themselves to better health." The
      coalition is presented as an organization that focuses on community empowerment
      and development. The stages of coalition development and implications for
      coalition implementation in other sites are discussed.

PMID- 9548062
TI  - Disease prevention and health promotion in urban areas: CDC's perspective.
AB  - The mission of the Centers for Disease Control and Prevention (CDC) is to prevent
      disease, injury, and premature death and to promote quality of life. This mission
      applies to all Americans, especially to the poor and underserved. As so many
      people who are impoverished live in America's urban areas, the CDC has a unique
      and specific interest in the health problems of our urban population. The CDC has
      established five priorities: (1) strengthen essential public health services, (2)
      enrich capacity to respond to urgent threats to health, (3) develop a nationwide
      prevention network and program, (4) promote women's health, and (5) invest in our
      nation's youth. Each of these priorities will contribute to improving the health
      of people living in urban areas. The CDC has recently undertaken numerous
      initiatives to address health promotion and disease prevention issues in the
      urban setting. Future directions for the CDC lie in better understanding the role
      of socioeconomic and cultural factors in promoting health and how resources
      within urban areas can be used to promote health. The CDC needs to explore
      potential relationships with various types of partners. Solving urban health
      problems requires actions from many federal agencies as well as from state and
      local organizations.

PMID- 9548063
TI  - Symptoms of acute myocardial infarction: expectations of a community sample.
AB  - OBJECTIVE: To identify the lay public's expectations of the symptoms of acute
      myocardial infarction (AMI). DESIGN: Street-intercept survey method. SETTING:
      Four neighborhoods in a large metropolitan area. SAMPLE: One hundred ninety-seven
      women and 217 men. INSTRUMENT: The Representation of Heart Attack Symptoms
      questionnaire (RHAS), a 48-item instrument that identifies subjects' expectations
      concerning the associated symptoms of AMI and the location, quality, and
      intensity of the discomfort of AMI. RESULTS: The symptoms most individuals
      expected during AMI included: chest pain, irregular heart beats, inability to
      move, and shortness of breath. The locations selected as most likely included:
      middle, left, and right side of the chest, upper and lower back. The most common
      descriptors of the expected discomfort were "tight," "pressure," and "heaviness."
      More than 88% of subjects expected the intensity of a heart attack to be at least
      a 9 on a scale of 0 (No discomfort) to 10 (The most discomfort imagined).
      CONCLUSIONS: The lay public have both accurate and inaccurate expectations about
      the symptoms of AMI.

PMID- 9548064
TI  - Taiwanese patients' concerns and coping strategies: transition to cardiac
      surgery.
AB  - OBJECTIVE: To explore patients' concerns during the admission transition to
      cardiac surgery. DESIGN: A descriptive qualitative design. SETTING: Four
      hospitals in northern Taiwan, Republic of China. PATIENTS: A purposive sample
      consisting of 40 adult patients (20 men and 20 women) who planned to have cardiac
      surgery. Age range was 20 to 70 years (mean 50.1 years). OUTCOME MEASURES: The
      types, levels, components, coping strategies, context, and conceptual framework
      of patients' concerns. INTERVENTION: Data were collected through semistructured
      interviews, and then analyzed using qualitative content analysis. RESULTS: Ninety
      percent of subjects (N = 36) reported two types of concerns: certain (80%) and
      uncertain (10%). Their certain concerns reflected three levels of concerns:
      "Caring about" or "Thinking about" (52%); "Worrying about" or "Being afraid of"
      (43%); and "Experiencing a mortal fear of" (30%), ordered from the weakest to the
      strongest. The components of patients' concerns were the process of recovery;
      hospital experiences, including maintaining daily activities, pain at admission,
      and expectant discomforts and disabilities in the intensive care unit; death;
      unfinished responsibilities and life goals, significant persons, and places;
      financial needs; and poor quality of care. Strategies developed to manage their
      concerns included (1) The use of person-focused effort (both cognitive and
      psychomotor), (2) Seeking help from others, including family members, friends,
      other patients, and health professionals, and (3) Turning to metaphysical power.
      The context for the phenomenon of Taiwanese subjects' concerns concerning cardiac
      surgery during the admission transition were "Being a person," resuming
      normality, and empowerment of self. CONCLUSION: The types, levels, components,
      and coping strategies of patients' concerns during the admission transition to
      cardiac surgery were discovered and delineated. The background context and
      conceptual framework for the phenomenon also were developed from the data
      analysis to describe and depict this phenomenon.

PMID- 9548065
TI  - Continuous positive airway pressure: patients' and caregivers' learning needs and
      barriers to use.
AB  - OBJECTIVE: To identify learning needs and factors related to postdischarge use of
      continuous positive airway pressure (CPAP) ventilation. DESIGN: Exploratory
      descriptive correlational. SETTING: Metropolitan and rural clinics. SUBJECTS:
      Adult patients (N = 21) and family caregivers, one half 60 years or older.
      INSTRUMENTS: Family interviews, life satisfaction and quality, family function
      and relationship, depression and learning preparedness. RESULTS: There were
      numerous learning needs related to CPAP machine management, monitoring illness
      severity, and recognizing depressive symptomology, oxygen deficits, and
      cardiovascular sequelae. Family members are involved in overcoming barriers
      interfering with nightly CPAP use. Interview and questionnaire data clearly
      indicate life satisfaction improves after CPAP treatment. CONCLUSION:
      Predischarge and teaching programs coordinated by expert nurses are needed to
      address families' learning needs and support habitual long-term CPAP use. Family
      problem solving and depression interventions, instruction on recognizing symptoms
      of cardiovascular complications, and long-term follow-up programs are currently
      being studied.

PMID- 9548066
TI  - Effects of specialized community nursing care in patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To investigate the effects of specialized respiratory home nursing
      care after discharge from a pulmonary rehabilitation center. DESIGN: Pretest
      posttest control group design. Patients in the experimental group were visited by
      a nurse who specializes in respiratory care, whereas the control group received
      care from nurses who did not specialize in respiratory care. SETTING: Data were
      collected on admission, at program discharge, and 4 months and 9 months after
      discharge from a pulmonary rehabilitation center. PATIENTS: One hundred fifteen
      patients were included in the study and observed for 1 year. OUTCOME MEASURES:
      Health-related quality of life (HRQL), coping strategies, compliance,
      hospitalization, and satisfaction with the care provided. RESULTS: Complete data
      sets were obtained from 78 patients with severe airflow obstruction (FEV1 = 41%;
      predicted +/- SD = 15). Corrections were made for the selective nonresponse, but
      did not lead to adjustments in outcome scores. In both groups, HRQL scores
      improved between admission and discharge, but deteriorated 4 months and 9 months
      after discharge. The only statistically significant short-term effect was found
      on the "activities" component of HRQL in favor of the control group. No
      differences were found between groups regarding coping, compliance, and
      hospitalization. Patients in the experimental group, however, were more satisfied
      with the care provided by the specialized community nurses. CONCLUSIONS: The
      treatment intervention of specialized respiratory home nursing might not have
      been specific or intensive enough to result in outcome benefits. Secondly, the
      initial benefits from baseline pulmonary rehabilitation alone may have led to
      positive outcomes in both patient groups.

PMID- 9548067
TI  - Bilioptysis: a sign of pulmonary capillary permeability injury.

PMID- 9548068
TI  - Pain and distress among elderly intensive care unit patients: comparison of
      patients' experiences and nurses' assessments.
AB  - OBJECTIVE: To investigate elderly intensive care unit (ICU) patients' experiences
      of pain and distress, as well as interventions aimed at reducing these
      conditions, and to compare these experiences with the way nurses and assistant
      nurses, respectively, assess their patients' responses related to these issues.
      DESIGN: Descriptive, correlational, comparative. SETTING: Two medical-surgical
      ICUs at county hospitals in two medium-sized cities in Sweden. SUBJECTS: Fifty
      one elderly patients, 44 nurses, and 37 assistant nurses in two Swedish ICUs.
      METHODS: Data were collected through personal interviews with patients and
      questionnaires completed by each nurse and assistant nurse responsible for the
      patients. RESULTS: Patients' experiences of pain and distress do not fully agree
      with nurses' and assistant nurses' assessments; nor is there consistency between
      the views of nurses and those of assistant nurses. Nurses overestimated patients'
      breathing and intellectual problems. Assistant nurses assessed that patients
      received more assistance to relieve physical pain, physical discomfort, fatigue,
      and fear than patients reported. Compared with nurses' assessments, assistant
      nurses also perceived patients to suffer less from physical discomfort, breathing
      problems, and fatigue. CONCLUSIONS: Nurses need more systematic procedures to
      assess patients' distress and pain experiences. To reduce the discrepancies
      observed between nurses and assistant nurses, organization of care should
      optimize the possibilities for the caregivers to carry out the desired
      assessments and interventions with a high degree of continuity and communication
      among staff.

PMID- 9548069
TI  - Decision making of nurses practicing in intensive care in Canada, Finland,
      Northern Ireland, Switzerland, and the United States.
AB  - In this study, our intention was to describe the decision making of nurses
      practicing in intensive care, and the differences of nurses' decision making in
      Canada, Finland, Northern Ireland, Switzerland, and the United States. The
      instrument used in the study was a 56-item Likert-type questionnaire that has
      been used in previous studies and has proved to be a reliable tool. The target
      group comprised a nonrandom sample of nurses (N = 314) from five countries. The
      samples are not representative; therefore, the results in these cases cannot be
      generalized. The results showed that the decision making of nurses practicing in
      intensive care was broadly based, and that there were some country differences in
      data collection, problem definition, and planning. In contrast, decision making
      related to the implementation and evaluation of nursing is quite similar in the
      different countries. Canada and the United States on the one hand, and Finland,
      Northern Ireland, and Switzerland on the other, showed more similarities with
      each other in data collection, problem definition, and nursing planning related
      to decision making. Neither experience nor nurse's knowledge structure was
      associated with different decision-making approaches.

PMID- 9548070
TI  - Tuberculous bronchoesophageal fistulae in patients infected with the human
      immunodeficiency virus: a case report and review.

PMID- 9548071
TI  - Proteus penneri urosepsis in a patient with diabetes mellitus.
AB  - Proteus penneri has been isolated from many different clinical sources, including
      surgical wound infections, urine, and blood. We describe the first reported case
      of P. penneri nosocomial urosepsis in a patient with diabetes. P. penneri was
      subsequently isolated from bronchoalveolar lavage fluid and a pulmonary artery
      catheter tip.

PMID- 9548072
TI  - Bidirectional tachycardia.

PMID- 9548073
TI  - Repertoire breadth of human CD4+ T cells specific for HIV gp120 and p66 (primary
      antigens) or for PPD and tetanus toxoid (secondary antigens)
AB  - Antigen derived peptides bound on MHC class II molecules on presenting cells
      stimulate specific CD4 lymphocytes that are in a naive state if antigen is given
      for the first time, or in a memory state if antigen has been previously
      encountered. In order to compare clonal heterogeneity of the human CD4+ T helper
      repertoire in primary vs. recall responses, we have generated T cell lines in
      vitro by repeated stimulation of peripheral lymphocytes with primary or with
      recall antigens. Clonal heterogeneity was broad in the case of recall response to
      tetanus toxoid or PPD, with a high frequency of specific precursors (> 100
      cells/10(6) lymphocytes). In contrast, T cell lines responsive to primary
      antigens (HIV gp120 or HIV p66) were oligoclonal as defined by TCR V beta gene
      usage and by spectratyping, and the precursor frequency was low (< 2 cells/10(6)
      lymphocytes). Primary T cell lines generated from blood samples drawn at
      different times from the same donor showed that clones with identical TCR CDR3
      region coding sequences were expanded, suggesting that in these individuals a
      large progeny derived from one single precursor is present, even though a
      previous encounter with the antigen was not documented. Assuming an even in vivo
      distribution of such cells, the presence of one precursor every 10(6) CD4
      lymphocytes (within the CD4 T repertoire that comprises roughly 10(11) CD4 T
      cells) indicates that approximately 10(5) identical T cells from the same clonal
      precursor account for the primary response against the model antigens we have
      studied.

PMID- 9548074
TI  - Promiscuous T-cell recognition of a rubella capsid protein epitope restricted by
      DRB1*0403 and DRB1*0901 molecules sharing an HLA DR supertype.
AB  - Two T cell clones derived from different donors with HLA-DRB1*0403 or DRB1*0901
      phenotype recognize a rubella capsid peptide, C(265-273) in the context of
      several different HLA-DR molecules in addition to DRB1*0403 and DRB1*0901. All DR
      molecules restricting the T-cell clones have in common residues, R or Q at
      position beta 70, R at position beta 71, and E at position beta 74 in pocket '4'
      of the DR peptide binding groove, suggesting that a DR subregion structure or
      supertype, "Q/RRE" underlies the promiscuous T-cell recognition of this peptide.
      Single amino acid substituted analogs of peptide C(263-275) at anchor position 4
      for natural residue R were tested for their ability to induce clonal T-cell
      cytotoxic responses. The results indicated that a positively charged residue, R
      or K, was required for T-cell recognition, suggesting a possible mechanism of
      electrostatic interactions between the negatively charged residue E at position
      beta 74 of these DR molecules and the positively charged residue at anchor
      position 4 of the peptide in T-cell recognition.

PMID- 9548075
TI  - Genetic and immunologic studies of patients on procainamide.
AB  - Forty (40) patients with cardiac arrhythmias receiving procainamide (PA) therapy
      and 24 patients who were receiving other drugs for their cardiac disorders were
      investigated for class II HLA phenotypes and their DRB1*04 and DQB1*03 subtypes.
      Other genetic marker evaluations in the PA patients included: 1) class III MHC
      C4A and C4B null alleles of complement; and, 2) acetylation phenotype. Twenty
      (20) of the PA patients were also tested for the ability of their stimulated
      cells to secrete Interleukin-1 (IL-1 beta) and tumor necrosis factor (TNF alpha).
      We also examined the spontaneous production of these cytokines by peripheral
      blood leukocytes (PBL) from patients who were receiving chronic PA treatment. The
      results revealed no association of acetylation phenotypes with the class II HLA
      phenotypes nor class III MHC C4 allotypes in these patients. The results did show
      a significant increase in class III C4 complement allotypes in the PA patients
      when compared to the controls. The results also showed a significant increase in
      autoantibodies and DQw3 phenotypes in the PA patient group when compared to
      control populations. Results of spontaneous IL-1 and TNF production suggested
      there may be an association of select class II HLA phenotypes in some patients
      and this may be relevant to host responsiveness to PA treatment.

PMID- 9548076
TI  - HLA-DQ2-negative celiac disease in Finland and Spain.
AB  - Genetic susceptibility to celiac disease (CD) is strongly associated with
      DQA1*0501 and DQB1*02 (= DQ2). To study whether CD patients without DQ2 share
      other MHC class II or TNF alleles, we screened DQ2-negative patients in Finland
      and Spain. Twelve of 84 (14%) Finnish patients and 13 of 189 (6%) Spanish
      patients were negative for DQ2. We observed that all but two of altogether 25 DQ2
      negative patients had the DR4 DQ8 haplotype, or either DQA1*0501 or DQB1*02
      alone. Also, all but three were positive for DRB4*01. The only patients without
      any of these alleles were both positive for DR 13. There was a clear difference
      between Finland and Spain: Ten (83%) of the 12 Finnish DQ2-negative patients but
      only five (38%) of the 13 Spanish patients had DRB1*03, DQA1*03, DQB1*0302 (=
      DQ8) alleles. Of the Spanish patients, eight (62%) had DQB1*02 without DQA1*0501
      and three (23%) had DQA1*0501 without DQB1*02. None of the TNF, TAP, or DPB1
      alleles was found to be significantly associated with CD. Our results indicate
      that in addition to the DQ2 heterodimer, the other major risk alleles for CD are
      DR4 DQ8, and either DQA1*0501 or DQB1*02 alone. Patients without these alleles
      appear to be very rare, only two (0.7%) were identified in altogether 253
      patients tested.

PMID- 9548078
TI  - HLA-DRB1*0405 is the predominant allele in Brazilian patients with Vogt-Koyanagi
      Harada disease.
AB  - Vogt-Koyanagi-Harada (VKH) disease is a rare disorder affecting pigmented
      structures especially the eye and is the main cause of autoimmune non-infectious
      uveitis in the Brazilian population. The autoimmune target is believed to be the
      melanocyte. A strong association of VKH disease with HLA-DR4 in the Japanese
      population is well known. The same association, albeit with lower relative risks
      has been found in other populations. A secondary association to HLA-DR1 involving
      a sequence linked with susceptibility to Rheumatoid Arthritis has also been
      described. VKH disease is more common in non-Caucasian populations. Brazilian
      patients of varying ethnic origins have been typed for HLA class II antigens.
      Several of the features found in other population samples are present. Over half
      of the patients typed HLA-DR4 (20/37) and typing with sequence-specific
      oligonucleotides disclosed predominance of the DRB1*0405 allele with a relative
      risk of 11.76 over the general population. In addition, HLA-DR1 and DQ4 were also
      present, in patients both positive and negative for HLA-DR4. These results
      suggest that, as in other autoimmune diseases, multiple overlapping
      susceptibility factors encoded by the MHC complex contribute to the overall
      susceptibility for the disease, the major factor however, being the presence of
      the DRB1*0405 allele.

PMID- 9548077
TI  - Major histocompatibility class II genes polymorphism in insulin dependent
      diabetes mellitus with or without associated thyroid autoimmunity.
AB  - Insulin dependent diabetes mellitus (IDDM) is sometimes associated with
      extrapancreatic organ-specific autoimmune diseases, but whether this phenotype
      results from a peculiar genetic profile is still unclear. The allelic
      distribution of the major histocompatibility complex (MHC) class II genes (HLA
      DRB1, DQA1, DQB1 and TAP) was analysed in 143 patients with IDDM alone by
      comparison with 82 IDDM patients with autoimmune thyroid disease (IDDM/AITD). The
      frequency of the DQB1*0301 IDDM-protective phenotype seemed to be lower in IDDM
      than in IDDM/AITD patients (16.8% vs 30.5% respectively, p = 0.02). By contrast,
      the frequency of the DRB1*04-DQB1*0302 IDDM-predisposing phenotype was higher in
      IDDM than in IDDM/AITD patients (91.3% vs 76.1% of DR4-positive patients
      respectively, p = 0.007), but these differences were not significant after
      correcting the p values, except in the case of the DRB1*0405-DQB1*0302
      combination (21.3% vs 2.4% of DR4-positive patients, Pc = 0.05). Furthermore, all
      differences disappeared when patients were matched for age at IDDM-onset. Our
      data do not long give support for a particular role of MHC class II genes in
      favouring the occurrence of thyroid autoimmunity in IDDM patients, but rather
      suggest that some class II alleles or residues might determine the rapidity of
      progression to IDDM in genetically susceptible individuals. The involvement of
      non-MHC genes and/or environmental factors remains to be determined.

PMID- 9548079
TI  - HLA-DP epitope typing using monoclonal antibodies.
AB  - We have made a panel of murine anti-DP monoclonal antibodies for serological
      typing of HLA-DP polymorphisms; they can be used in microcytotoxicity (for 7
      epitopes) and binding assays (for 8 epitopes). The antibodies detect polymorphic
      differences in both alpha and beta chains. As immunogens we sometimes used B
      lymphoblastoid lines or purified DP molecules but mostly used mouse fibroblast
      transfectants expressing DP molecules. The DP beta genes were made from a cloned
      DPB1*0201 gene by replacing its major area of polymorphism with matching
      stretches of DNA amplified from other alleles; cloned DPA1*01 and DPA1*02 genes
      were used for transfection along with the beta chain genes. The monoclonal
      antibodies showed reaction patterns that correlated with the presence of
      particular amino-acid sequence motifs; thus none of the antibodies is allele
      specific. They bind instead to epitopes which are found on a number of different
      HLA-DP types. We have constructed frequency tables so that the epitope (motif)
      data can be interpreted as the most likely genotype in each case. The basic
      assumption to justify this work is that HLA-DP matching or mismatching will
      likely influence transplant outcome, particularly in bone marrow transplantation.
      The present challenge is to define permissive and nonpermissive combinations of
      HLA-DP; it may be that matching for epitopes, rather than for full alleles, will
      help to resolve this issue.

PMID- 9548080
TI  - Optical tomography for biomedical applications.

PMID- 9548081
TI  - Developments in ECG acquisition, preprocessing, parameter measurement, and
      recording.

PMID- 9548082
TI  - Improving instrumentation for hospital care of neonates in Hungary. A system to
      help reduce the rate of perinatal mortality.

PMID- 9548083
TI  - PC-based noninvasive measurement of the autonomic nervous system. Detecting the
      onset of diabetic autonomic neuropathy.

PMID- 9548084
TI  - Nonlinear filtering and fast ray tracing of 3-D Image data. Improving
      visualization in medical imaging.

PMID- 9548085
TI  - Early detection of Parkinson's disease through automatic movement evaluation.

PMID- 9548087
TI  - Applying nonlinear dynamics to ECG signal processing. Two approaches to
      describing ECG and HRV signals.

PMID- 9548086
TI  - Tracking EEG signal dynamics during mental tasks. A combined linear/nonlinear
      approach.

PMID- 9548088
TI  - Specific processing of the spontaneous EMG. Detection and classification of
      multiplets using self-organizing neural networks.

PMID- 9548089
TI  - Advantages of stereological methods in biomedicine. Efficiently obtaining
      unbiased estimates of geometrical characteristics for 3-D structures.

PMID- 9548090
TI  - Gene Alert--a sequence search results keyword parser.

PMID- 9548091
TI  - Science in the Supreme Court: round two.

PMID- 9548092
TI  - Symptomatic colonic lipoma: differential diagnosis of large bowel tumors.
AB  - Symptomatic colonic lipomas, although unusual, continue to present difficulties
      in the preoperative differential diagnosis between malignant and benign colonic
      neoplasm. Although new imaging techniques are available, they are frequently
      diagnosed at laparotomy, and definitive histology is required. Local excision is
      adequate treatment, but segmental excision may be necessary when there is doubt
      about the diagnosis, or when a complication occurs.

PMID- 9548093
TI  - Hereditary non-polyposis colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant
      condition in which affected individuals develop colorectal cancer or extracolonic
      cancers, most commonly endometrial, at an early age. Recent advances in molecular
      genetics have led to the identification and sequencing of four genes thought to
      be responsible for the majority of cases of hereditary non-polyposis colorectal
      cancer. A description of the disease along with details of the underlying
      genetics and pathological features are presented. Current management and
      screening policies in these pedigrees are not clearly established. This article
      discusses some of the controversies in the light of predictive testing.

PMID- 9548094
TI  - Rectocele is associated with paradoxical anal sphincter reaction.
AB  - Rectocele is a frequent finding in constipated patients. However, constipation is
      not always relieved by rectocele repair, which may be due to other overlooked
      reasons for constipation. The study was designed to investigate patients with
      rectocele, in order to elucidate concomitant colorectal disorders and their
      association with rectocele. One hundred and twelve female patients suffering from
      severe constipation and rectal emptying difficulties were investigated using
      defecography, electrophysiology, anorectal manometry and colon transit time.
      Fifty-six patients with rectocele demonstrated by defecography were compared with
      56 patients without rectocele, but with other abnormal findings at defecography.
      The frequency of paradoxical anal sphincter reaction (PSR) was higher in patients
      with rectocele (60%) than in patients without rectocele (24%). The present study
      supports an association between rectocele and PSR. We suggest that constipated
      patients with a rectocele should be investigated thoroughly before rectocele
      repair is considered. Further studies on the effect of biofeedback training in
      patients with rectocele and PSR are indicated.

PMID- 9548095
TI  - Terminal ileal transposition procedure in ileoanal anastomosis following
      proctocolectomy.
AB  - We introduced a terminal ileal transposition procedure (TITP) in ileal pouch-anal
      anastomosis, in which a 50 to 70 cm isolated ileal segment 20 to 40 cm from the
      ileocecal valve was interposed between the terminal ileum and the anus. Twelve
      patients underwent this procedure in two or three-staged operations. Mean stool
      frequency per 24 hours was 4.4 +/- 1.7, and stool consistency was formed and soft
      in all patients at the mean of 13 months after TITP. We observed neither surgical
      technique-related complications nor metabolic disorders, except for iron
      deficiency anemia, during and after the operations. The serum level of vitamin
      B12 significantly increased after the operation in eight patients (P < 0.05).
      TITP has advantages such as preventing the terminal ileum from metabolic
      dysfunction due to pouchitis, avoiding sacrifice of the terminal ileum in the two
      staged operation, and obviating the need for reconstruction of ileostomy in the
      three-staged operation. It may also promote intestinal absorption and reduce late
      metabolic complications.

PMID- 9548096
TI  - Relationship between anal canal diameter and pressure evaluated simultaneously by
      endosonography and manometry in normal human subjects.
AB  - The study investigated the relationship between anal canal size and anal canal
      pressure measured simultaneously by anal endosonography and an electronic
      pressure probe. Twelve normal subjects were studied. Anal endosonography was
      performed using a 7.5-Mhz rotating transducer of 2-5 cm focal length covered with
      a sylastic balloon filled with degassed water (25 ml). During anal endosonography
      an electronic manometric probe was passed along the side of the probe and
      positioned in the anal canal. The ultrasonic image was frozen when maximal anal
      pressure was seen at basal, squeeze, and minimal pressure during straining. An
      image was also obtained at maximal anal relaxation after rectal distension with a
      balloon filled with 150 ml air. The results showed that anal canal pressure was
      significantly and linearly correlated with anal canal diameter (P < 0.001).

PMID- 9548097
TI  - Delay in the presentation of colorectal carcinoma: a review of causation.
AB  - This review paper studies the reasons behind the delay in presentation of
      colorectal carcinoma. Such delay can occur at three different levels: delay on
      the part of the patient, delay by the general practitioner prior to patient
      referral and delay incurred at the hospital after patient referral. There is some
      evidence that patient delay has decreased in recent years; general practitioner
      delay is disputed by some authors, but there is considerable evidence that it
      exists. Hospital delay can be influenced by the general practitioner; there is
      evidence that it has increased in recent years and is likely to increase further
      with the current pressure on in-patient beds.

PMID- 9548098
TI  - Surgery for local pelvic recurrence after resection of rectal cancer.
AB  - This retrospective study evaluated outcome with regard to procedure, local
      control, and survival after curative surgical resection with and without
      preoperative radiotherapy for local pelvic recurrence. A total of 58 consecutive
      patients with local pelvic recurrence of rectal cancer after previous curative
      resection for primary tumors were reviewed. Of these, 36 underwent both initial
      resection and follow-up in our department; the remaining 22 had initial surgery
      and follow-up elsewhere. Of the 58 patients 27 underwent curative re-resection, 9
      had palliative resection, and 22 were treated by conservative therapy. Among the
      27 patients with curative resection 17 received preoperative radiotherapy (40 Gy)
      plus surgery and 10 surgery only. No patients were lost to follow-up; median
      follow-up time was 36.3 months. The overall rate of curative resection was 46.6%:
      55.6% in our own follow-up group and 31.8% in the others. With regard to surgical
      procedure, abdominoperineal resection (APR) with or without sacral resection was
      standard following previous low anterior resection, and total pelvic exenteration
      (TPE) with or without sacral resection was common following APR. There was a high
      incidence of morbidity (71.4%) after TPE. Re-recurrence was observed in 12
      (44.4%) after curative re-resection. There was local re-recurrence in 6 (22.2%).
      The local re-recurrence rate was 11.8% (n = 2) with radiotherapy plus surgery,
      and 40.0% (n = 4) with surgery alone. The estimated 5-year survival following
      curative re-resection was 45.6% (61.2% with radiotherapy plus surgery, 29.6% with
      surgery alone). Both survival and local control with radiotherapy plus surgery
      tended to be better than with surgery alone. Thus, in selected patients pelvic
      local recurrence of rectal cancer can be re-resected curably by APR or TPE (with
      or without sacral resection) combined with preoperative radiotherapy.

PMID- 9548099
TI  - Prophylactic pancreaticoduodenectomy for premalignant duodenal polyposis in
      familial adenomatous polyposis.
AB  - The frequency of duodenal adenomas in patients with, familial adenomatous
      polyposis is high. Duodenal adenoma has malignant potential, and duodenal
      adenocarcinoma is one of the main causes of death in patients who have had
      previous proctocolectomy. A conservative approach to the treatment of duodenal
      adenomas (nonsteroidal anti-inflammatory drugs, endoscopy, polypectomy through
      duodenotomy) is inefficient and unsafe. When invasive cancer occurs in duodenal
      adenomas, the result of surgery is poor. We have performed prophylactic
      pancreaticoduodenal resection (PDR) for nonmalignant severe duodenal polyposis in
      five patients since 1991. No operative mortality was observed. One patient
      developed a pancreatic fistula which was successfully managed by medical
      treatment. The mean follow-up was 35 months. All five patients are still alive
      and have a good functional outcome. Prophylactic PDR may be indicated in familial
      adenomatous polyposis when duodenal polyposis is severe. Stages III and IV of
      Spigelman's classification, periampullary adenoma, age above 40, and family
      history of duodenal cancer are factors that may lead to the decision to perform
      prophylactic PDR.

PMID- 9548100
TI  - Laparoscopic colorectal resection for diverticulitis.
AB  - This study evaluated outcome in patients undergoing laparoscopically assisted
      sigmoid resection for diverticular disease. A total of 29 consecutive patients
      were treated surgically for colonic diverticulitis; in 27 of these laparoscopy
      was performed. The review of medical records from a control group of 34 patients
      undergoing open resection were used for comparison. The conversion rate was 7.5%.
      Using the laparoscopic technique the duration of surgery was longer (165 vs. 121
      min, P < 0.05), blood loss less (182 vs. 352 ml, P < 0.05), and subsequent blood
      transfusion less (0 vs. 61%). The incidence of complications following
      laparoscopic resection was lower (two anastomotic leakages, two wound infections)
      than in the conventional group. Convalescence in the laparoscopic group was more
      rapid and hospital stay shorter (7.9 vs. 14.3 days, P < 0.05). In the
      laparoscopic group patients expressed less pain at rest and in motion. The cost
      of the laparoscopically assisted procedure was less than that of conventional
      resection (7185 vs. 8975 DM). In this series laparoscopically assisted sigmoid
      resection for diverticulitis proved safe. Recovery was faster, hospital stay was
      shorter, and patients expressed less pain than in conventional open surgery.

PMID- 9548101
TI  - Necrotizing perineal infections (Fournier's disease): old remedies for an old
      disease.
AB  - Perineoscrotal gangrene (Fournier's disease, a specific type of necrotizing
      fasciitis) is a rare and potentially fatal clinical entity characterized by
      progressive spread of necrosis in the skin and subcutaneous tissues combined with
      severe systemic sepsis. We analyzed retrospectively seven patients with
      perineoscrotal gangrene, illustrating the various clinical presentations,
      problems in management, and specific approaches to therapy. On admission all
      patients were evaluated as being in critical condition, having severe systemic
      disease and rapidly advancing gangrene. After hemodynamic stability was achieved
      broad spectrum antibiotics were started, and aggressive surgical treatment
      initiated. In all the patients the infection originated from the anorectal area
      and proved to be polymicrobial in nature. Six patients survived and were able to
      be discharged from hospital there was one death on the fifth postoperative day
      due to pulmonary embolism. The crucial points in the management of this infection
      remains early diagnosis, wide and repeated surgical debridements, and appropriate
      antibiotic therapy.

PMID- 9548102
TI  - Improved determination of terminal pudendal latency by modification of the
      standard electrode.

PMID- 9548103
TI  - Internal anal sphincter repair.

PMID- 9548104
TI  - Pathological features of rectal cancer after preoperative radiochemotherapy.

PMID- 9548105
TI  - What price glory?

PMID- 9548106
TI  - Prospective evaluation of the Ottawa Ankle Rules in a university sports medicine
      center. With a modification to increase specificity for identifying malleolar
      fractures.
AB  - In a sports medicine center, we prospectively evaluated the Ottawa Ankle Rules
      over 1 year for their ability to identify clinically significant ankle and
      midfoot fractures and to reduce the need for radiography. We also developed a
      modification to improve specificity for malleolar fracture identification.
      Patients with acute ankle injuries (< or = 10 days old) had the rules applied and
      then had radiographs taken. Sensitivity, specificity, and the potential reduction
      in the use of radiography were calculated for the Ottawa Ankle Rules in 132
      patients and for the new "Buffalo" rule in 78 of these patients. There were 11
      clinically significant fractures (fracture rate, 8.3% per year). In these 132
      patients, the Ottawa Ankle Rules would have reduced the need for radiography by
      34%, without any fractures being missed (sensitivity 100%, specificity 37%). In
      78 patients, the specificity for malleolar fracture for the new rule was
      significantly greater than that of the Ottawa Ankle Rules malleolar rule (59%
      versus 42%), sensitivity remained 100%, and the potential reduction in the need
      for radiography (54%) was significantly greater. The Ottawa Ankle Rules could
      significantly reduce the need for radiography in patients with acute ankle and
      midfoot injuries in this setting without missing clinically significant
      fractures. The Buffalo modification could improve specificity for malleolar
      fractures without sacrificing sensitivity and could significantly reduce the need
      for radiography.

PMID- 9548107
TI  - Achilles tendinosis and calf muscle strength. The effect of short-term
      immobilization after surgical treatment.
AB  - We prospectively studied calf muscle strength in 7 men and 4 women (mean age,
      40.9 +/- 10.1 years) who had surgical treatment for chronic Achilles tendinosis.
      Surgery was followed by immobilization in a weightbearing below-the-knee plaster
      cast for 2 weeks followed by a stepwise increasing strength training program.
      Strength measurements (peak torque and total work) were done preoperatively (Week
      0) and at 16, 26, and 52 weeks postoperatively. We measured isokinetic concentric
      plantar flexion strength at 90 and 225 deg/sec and eccentric flexion strength at
      90 deg/sec on both the injured and noninjured sides. Preoperatively, concentric
      and eccentric strength were significantly lower on the injured side at 90 and 225
      deg/sec. Postoperatively, concentric peak torque on the injured side decreased
      significantly between Weeks 0 and 16 and increased significantly between Weeks 26
      and 52 at 90 deg/sec but was significantly lower than that on the noninjured side
      at all periods and at both velocities. The eccentric strength was significantly
      lower on the injured side at Week 26 but increased significantly until at Week 52
      no significant differences between the sides could be demonstrated. It seems,
      therefore, that the recovery in concentric and eccentric calf muscle strength
      after surgery for Achilles tendinosis is slow. We saw no obvious advantages in
      recovery of muscle strength with a short immobilization time (2 weeks) versus a
      longer (6 weeks) period used in a previous study.

PMID- 9548108
TI  - Effects of nonsteroidal antiinflammatory medication on satellite cell
      proliferation during muscle regeneration.
AB  - Previous experimental studies have indicated delayed muscle regeneration after
      nonsteroidal antiinflammatory drug therapy. Successful regeneration of muscle
      after injury requires activation of normally dormant satellite cells that share
      the basal laminae with adjacent muscle cells. In the presence of adequate
      capillary ingrowth, satellite cells proliferate into myotubes and eventually form
      new muscle cells. In this study, the onset and extent of satellite cell and
      fibroblast proliferation as well as the production of myotubes and capillaries
      were analyzed with immunohistochemical methods after contusion injuries to rats'
      gastrocnemius muscles. Two groups of animals received daily doses of an
      intramuscular nonsteroidal antiinflammatory drug (naproxen) starting 6 hours and
      3 days after injury, respectively. Treated animals were compared with similarly
      injured untreated animals. Satellite cell and fibroblast proliferation were
      unaffected by the treatment, and there were no significant differences in myotube
      or capillary production between treated and control animals. We conclude that
      naproxen treatment does not compromise the basic process of myofiber regeneration
      after injury.

PMID- 9548109
TI  - Occurrence of cervical spine injuries during the rugby scrum.
AB  - A retrospective study of cervical spine injuries that occurred during the rugby
      scrum in the United States was undertaken. In the U.S., from 1970 to 1996, 36
      (58%) of the 62 documented injured players injured their cervical spines during
      the scrum. Thirty-five men (97%) and one woman (3%) were injured. Twenty-three of
      the injuries (64%) occurred when the opposing packs came together (engagement),
      and 13 (36%) occurred when the scrum collapsed. Twenty-eight (78%) hookers, seven
      (19%) props, and one (3%) second-row player were injured. Twenty (56%) hookers
      and three (8%) props were hurt during engagement. Eight hookers (22%), four props
      (11%), and one second-row player (3%) were injured when the scrum collapsed.
      Significantly more injuries occurred during engagement than during collapse, and
      hookers were injured significantly more than props. We conclude that in the rugby
      scrum in the U.S., the hooker suffers most of the cervical spine injuries (78% in
      this study) and this position is by far the most vulnerable. This study should be
      used to develop rugby law (rule) changes and educate players, coaches, and
      referees in United States rugby.

PMID- 9548110
TI  - Five-year results of single-incision arthroscopic anterior cruciate ligament
      reconstruction with patellar tendon autograft.
AB  - We performed a retrospective study on 80 patients who underwent single-incision
      arthroscopic anterior cruciate ligament reconstruction with patellar tendon
      autograft and interference fit screw fixation in 1989. Twelve patients were lost
      to followup, allowing a clinical assessment of 68 patients to be conducted by
      independent examiners at 1 and 5 years after surgery, with radiographic
      assessment at 5 years. Thirty-three patients had chronic anterior cruciate
      ligament-deficient knees. Three patients reruptured their grafts during sports at
      29, 48, and 56 months. At 5 years, 64 patients (98%) had grade 0 or 1 Lachman and
      pivot shift tests with manual stability testing. Fifty patients (77%) were
      participating in level I or II activities according to the International Knee
      Documentation Committee scale. Twenty-nine patients (45%) experienced low levels
      of pain when performing at their highest activity level. Five (8%) had thigh
      atrophy greater than 1 cm, and three (5%) had an extension loss of more than 3
      degrees. Eleven patients (17%) had tenderness over the graft site when kneeling.
      Fifteen of 62 patients (24%) had degenerative changes on radiographs, and this
      was more common in patients with chronic anterior cruciate ligament-deficient
      knees. Fifty-two patients (80%) had normal or nearly normal knees according to
      the overall International Knee Documentation Committee score.

PMID- 9548111
TI  - Arthroscopic distal clavicle resection for isolated atraumatic osteolysis in
      weight lifters.
AB  - Ten consecutive patients with isolated atraumatic osteolysis of the distal
      clavicle who had failed results with conservative treatment were treated with
      arthroscopic resection of the involved distal clavicle (average, 4.5 mm). All
      patients were men with an average age of 30.4 years, had unilateral involvement,
      and were considered aggressive amateur to elite weight lifters or bodybuilders.
      Postoperative symptoms consisted of pain at the incision and discomfort from
      extravasation of the irrigation fluid. At an average followup of 18.7 months, all
      patients had returned to their sport (average, 3.2 days) and to their
      preoperative weight training program (average, 9.1 days). They continued to be
      asymptomatic throughout the follow-up period and were able to increase both their
      training volume and strength from preoperative levels. Limited arthroscopic
      resection of the distal clavicle for isolated atraumatic osteolysis is a viable
      alternative for the weight lifter or bodybuilder. The ability to continue
      training without significant interruption as well as a more acceptable cosmetic
      appearance are benefits for these patients. Limited arthroscopic resection of the
      distal clavicle may be sufficient for this entity in this patient population,
      rather than the 1 to 2 cm previously reported. A sport-specific functional
      outcome questionnaire has been developed for this patient population.

PMID- 9548112
TI  - Winner of the AlbertTrillat Young Investigator Award. The effects of aggressive
      notchplasty on the normal knee in dogs.
AB  - We assessed the possible association between an aggressive intercondylar
      notchplasty and histopathologic, radiographic, and gait changes to the knee.
      Three groups of six adult greyhounds were observed for 6 months. Group I dogs had
      a sham operation. Group II dogs had a 4-mm notchplasty of the lateral femoral
      condyle where it articulates with the lateral tibial spine. Group III dogs had a
      7- to 8-mm notchplasty of the lateral femoral condyle to simulate the long-term
      effects of an overly aggressive notchplasty. Force plate gait analyses were not
      significantly different for any dogs at 3 and 6 months. Histopathologic studies
      (hematoxylin and eosin and safranin O stains) revealed notchplasty area
      remodeling with a thin layer of lamellar bone covered by fibrous connective
      tissue. Both Group II and III dogs had significant loss of lateral femoral
      condyle and trochlear groove articular surface proteoglycans. The radiographic
      notch width index remained unchanged throughout the study for Group I; the
      indexes increased immediately after surgery in Groups II and III because of the
      notchplasty, but after 6 months these values returned to near-preoperative
      measurements. An aggressive intercondylar notchplasty caused articular cartilage
      histopathologic changes at 6 months consistent with those found in knees with
      early degenerative arthritis. Significant refilling of a non-impinged notchplasty
      occurred by 6 months after surgery. Our results raise concern about the effects
      of aggressive intercondylar notch widening in humans.

PMID- 9548113
TI  - The effects of removal and reconstruction of the anterior cruciate ligament on
      patellofemoral kinematics.
AB  - Patellofemoral pain may be associated with anterior cruciate ligament deficiency
      or may occur after anterior cruciate ligament reconstruction. We investigated the
      effects of the removal and reconstruction of the anterior cruciate ligament on
      the kinematics of the tibiofemoral and patellofemoral joints during physiologic
      levels of quadriceps muscle loads in seven cadaveric knees. A bone-patellar
      tendon-bone graft was used for intraarticular reconstruction of the anterior
      cruciate ligament. The spatial positions of the tibiofemoral and patellofemoral
      joints were measured between 0 degrees and 90 degrees of knee flexion in 15
      degrees increments with a six degree-of-freedom digitizing system. Excision of
      the anterior cruciate ligament resulted in statistically significant increases in
      anterior tibial translation between 0 degrees and 90 degrees and valgus tibial
      rotation between 30 degrees and 90 degrees; intraarticular reconstruction
      returned these to levels not significantly different from those of the intact
      knee. Excision of the anterior cruciate ligament resulted in significant
      increases in lateral patellar tilt, ranging from 6.3 degrees to 9.0 degrees
      between full extension and 90 degrees of knee flexion, and in lateral patellar
      shift, ranging from 2.9 mm at 15 degrees of knee flexion to 5.9 mm at 90 degrees;
      intraarticular reconstruction returned these to levels not significantly
      different from those of the intact knee. Neither removal nor reconstruction of
      the anterior cruciate ligament significantly affected tibial internal-external
      rotation, patellar flexion, patellar mediolateral rotation, patellar
      anteroposterior translation, or patellar proximodistal translation.

PMID- 9548114
TI  - Electromyographic activity and applied load during shoulder rehabilitation
      exercises using elastic resistance.
AB  - Muscle activity (measured by electromyography) and applied load were measured
      during seven shoulder rehabilitation exercises done with an elastic resistance
      device. Nineteen men with no shoulder abnormalities performed seven exercises:
      external and internal rotation, forward punch, shoulder shrug, and seated rowing
      with a narrow, middle, and wide grip. Qualitative video (60 Hz) was synchronized
      with the electromyography data from eight muscles (2000 Hz). Fine-wire
      intramuscular electrodes were inserted into the supraspinatus and subscapularis
      muscles, and surface electrodes were placed over the anterior deltoid,
      infraspinatus, pectoralis major, latissimus dorsi, serratus anterior, and
      trapezius muscles. Ten trials per subject were analyzed for average and peak
      amplitude, and the results were expressed as a percentage of maximum voluntary
      contractions. The peak loads for all exercises ranged from 21 to 54 N. The muscle
      activity patterns suggest that these shoulder rehabilitation exercises
      incorporating elastic resistance, controlled movements, and low initial loading
      effectively target the rotator cuff and supporting musculature and are
      appropriate for postinjury and postoperative patients.

PMID- 9548115
TI  - Early phase differential effects of slow and fast barbell squat training.
AB  - To examine the importance of resistance training movement speed, two groups of
      women (24 +/- 4 years, 162 +/- 5 cm, 59 +/- 7 kg) squatted repeatedly at 1) 2
      seconds up, 2 seconds down (slow, N = 11); or 2) 1 second up, 1 second down
      (fast, N = 10), doing three warm-up sets and three eight-repetition maximum sets,
      three times per week for 7 weeks. Tests included force platform and video
      analysis of the vertical jump, long jump, and maximum squat, and isometric and
      isokinetic knee extensor testing at speeds from 25 to 125 deg/sec. The groups
      improved similarly in many variables with training but also showed some
      differences. In the long jump, the fast group was superior in numerous variables
      including knee peak velocity and total-body vertical and absolute power. In the
      vertical jump, fast training affected the ankle and hip more (e.g., average
      power), and slow training mostly affected the knee (average torque). In
      isokinetic testing, the fast group improved strength most at the faster
      velocities, while the slow group strength changes were consistent across the
      velocities tested. Although both slow and fast training improved performance,
      faster training showed some advantages in quantity and magnitude of training
      effects.

PMID- 9548116
TI  - A new concept for isokinetic hamstring: quadriceps muscle strength ratio.
AB  - Conventionally, the hamstring:quadriceps strength ratio is calculated by dividing
      the maximal knee flexor (hamstring) moment by the maximal knee extensor
      (quadriceps) moment measured at identical angular velocity and contraction mode.
      The agonist-antagonist strength relationship for knee extension and flexion may,
      however, be better described by the more functional ratios of eccentric hamstring
      to concentric quadriceps moments (extension), and concentric hamstring to
      eccentric quadriceps moments (flexion). We compared functional and conventional
      isokinetic hamstring: quadriceps strength ratios and examined their relation to
      knee joint angle and joint angular velocity. Peak and angle-specific (50 degrees,
      40 degrees, and 30 degrees of knee flexion) moments were determined during
      maximal concentric and eccentric muscle contractions (10 degrees to 90 degrees of
      motion; 30 and 240 deg/sec). Across movement speeds and contraction modes the
      functional ratios for different moments varied between 0.3 and 1.0 (peak and 50
      degrees), 0.4 and 1.1 (40 degrees), and 0.4 and 1.4 (30 degrees). In contrast,
      conventional hamstring:quadriceps ratios were 0.5 to 0.6 based on peak and 50
      degrees moments, 0.6 to 0.7 based on 40 degrees moment, and 0.6 to 0.8 based on
      30 degrees moment. The functional hamstring:quadriceps ratio for fast knee
      extension yielded a 1:1 relationship, which increased with extended knee joint
      position, indicating a significant capacity of the hamstring muscles to provide
      dynamic knee joint stability in these conditions. The evaluation of knee joint
      function by use of isokinetic dynamometry should comprise data on functional and
      conventional hamstring:quadriceps ratios as well as data on absolute muscle
      strength.

PMID- 9548117
TI  - Concussion incidence in elite college soccer players.
AB  - A unique aspect of soccer is the use of the head for directing the ball. The
      potential for resultant head injuries has been the focus of discussions
      worldwide. Prior work has attributed neuropsychologic deficits to the cumulative
      effects of heading, without evaluating concussion rates in soccer players. We
      prospectively studied the seven men's and eight women's varsity soccer teams in
      the Atlantic Coast Conference during two seasons to document concussion
      incidence. The 29 concussions diagnosed over the 2 years in 26 athletes, 17 (59%)
      concussions in men and 12 (41%) in women, resulted from contact with an
      opponent's head (8, 28%), elbow (4, 14%), knee (1, 3%), or foot (1, 3%); the ball
      (7, 24%); the ground (3, 10%); concrete sidelines (1, 3%); goalpost (1, 3%); or a
      combination of objects (3, 10%). Twenty concussions (69%) occurred in games; none
      resulted from intentional heading of the ball. The basic incidence was 0.96
      concussions per team per season. The overall incidence was 0.6 per 1000 athlete
      exposures for men, and 0.4 per 1000 athlete-exposures for women. By concussion
      grade, there were 21 (72%) grade 1, 8 (28%) grade 2, and no grade 3 concussions.
      These findings suggest that concussions are more common in soccer than
      anticipated and that acute head injuries may have potential for long-term
      neuropsychologic changes.

PMID- 9548118
TI  - Throwing fracture of the humeral shaft. An analysis of 90 patients.
AB  - Ninety patients with humeral shaft fractures sustained during throwing were
      analyzed to determine what caused their injuries. All patients were recreational
      baseball players: 89 were men and 1 was a woman. The average age was 25 years
      (range, 12 to 43). The throwing style, type of pitch, fielding position, and type
      of ball used varied; however, the patients sustained their fractures while
      performing a hard throw in 87 (97%) of the occurrences. The actual courses of the
      balls thrown ranged from sideways to straight forward. All fractures were
      external rotation spiral fractures; 25 patients (28%) had a medial butterfly
      fragment, and 14 patients (16%) had radial nerve palsy. Fractures were most
      likely to have occurred in the distal half of the humerus, although they occurred
      frequently in the proximal half in patients in their early teens. We conclude
      that 1) the fracture can occur at any time during the acceleration phase before
      ball release, 2) this type of fracture can occur in any recreational baseball
      player attempting to perform a hard throw, and 3) the cause of this fracture is
      the throwing action itself.

PMID- 9548119
TI  - Humeral torsion in the throwing arm of handball players.
AB  - Sport-specific upper extremity strain, mostly unilateral, during growth may lead
      to adaptations in soft tissue and bone. We investigated 51 male professional
      handball players between 18 and 39 years of age (average, 27 years), 39 right
      handed and 12 left-handed. Thirty-eight players had no shoulder problems, and 13
      had chronic shoulder pain. Humeral retrotorsion was determined by radiograph. The
      differences between the throwing and contralateral arms were compared with those
      of 37 controls who had no history of unilateral strain either through sports or
      profession. Standard statistical analysis was performed using the t-test. The
      retrotorsional angle of the humerus in the handball professionals' throwing arm
      was an average of 9.4 degrees larger in the dominant side than in the
      nondominant, with a side-to-side difference up to 29 degrees. In the control
      group, no statistically significant difference was found. In the group without
      chronic shoulder pain, the side-to-side difference was an average of 14.4 degrees
      more in the throwing arm than the other side. Players with chronic shoulder pain
      did not exhibit this increase, even showing an average decrease of humeral
      retrotorsion of 5.2 degrees in the throwing arm. The humeral retrotorsion
      increase can be explained as an adaptation to extensive external rotation in
      throwing practice during growth. Athletes who do not adapt this way seem to have
      more strain on their anterior capsules at less external rotation and develop
      chronic shoulder pain because of anterior instability.

PMID- 9548120
TI  - Clinical, functional, and radiographic assessments of the conventional and
      modified Boyd-Anderson surgical procedures for repair of distal biceps tendon
      ruptures.
AB  - The purpose of this study was to evaluate the clinical, functional, and
      radiographic outcomes of the conventional and modified Boyd-Anderson procedures
      for repair of distal biceps tendon ruptures. Thirteen of 18 men who underwent
      surgical repair for unilateral distal biceps tendon ruptures at one university
      center participated in the study. In general, follow-up outcomes were favorable
      with respect to return to premorbid activity levels, patient satisfaction with
      surgical outcome, and overall clinical results. Elbow flexion, forearm
      supination, and upper extremity functional concentric peak torque and range of
      motion results were not significantly different between the surgical and
      nonsurgical arms when dominance was controlled as a confounding factor.
      Radiographic findings revealed no clinically remarkable signs of heterotopic
      ossification or proximal radioulnar synostosis. Results of the study reveal that
      the conventional and modified Boyd-Anderson procedures are clinically,
      functionally, and radiographically efficacious for repair of distal biceps tendon
      ruptures.

PMID- 9548121
TI  - The effects of muscle fatigue on shoulder joint position sense.
AB  - Proprioception, or joint position sense, probably plays an important role in
      shoulder joint function. In this study, we assessed the effect of muscle fatigue
      on shoulder proprioception in 20 volunteers with no shoulder abnormalities.
      Shoulder proprioception was measured as the threshold to first detection of
      humeral rotation with the joint at 90 degrees of abduction and 90 degrees of
      external rotation. Subjects were tested while rested, exercised on a isokinetic
      testing machine until fatigued, and then retested in an identical fashion. Both
      shoulders were tested, and the order of dominant and nondominant shoulder was
      randomized. Shoulder proprioception was analyzed for its dependence on arm
      dominance, direction of rotation, and muscle fatigue. Subjects detected external
      rotation after significantly less movement than they did internal rotation.
      Overall, before exercise, motion was detected after a mean of 0.92 degrees of
      rotation. After exercise, this threshold to detection of movement increased to
      1.59 degrees, an increase of 73%. This significant increase occurred with both
      internal and external rotation. The decrease in proprioceptive sense with muscle
      fatigue may play a role in decreasing athletic performance and in fatigue-related
      shoulder dysfunction. It remains to be determined if training can lessen this
      loss in position sense.

PMID- 9548122
TI  - The clinical diagnosis of subcutaneous tear of the Achilles tendon. A prospective
      study in 174 patients.
AB  - A study to determine the sensitivity, specificity, and positive and negative
      predictive values of several clinical diagnostic tests of subcutaneous Achilles
      tendon rupture was performed during a 13-year period. There were 174 patients
      with clinical diagnosis of unilateral complete subcutaneous Achilles tendon tear
      and 28 patients with unilateral suspected but no actual Achilles tendon tear. The
      following tests were used: palpation, calf squeeze, Matles, Copeland, and
      O'Brien. Palpation of the gap was the least sensitive clinical test with the
      patient awake (0.73), increasing to 0.81 when the test was performed under
      anesthesia; the Copeland and O'Brien tests showed a sensitivity of 0.8. Both the
      calf squeeze and Matles tests were significantly more sensitive than the other
      tests (0.96 and 0.88, respectively; 0.022 < P < 0.05). All tests showed a high
      positive predictive value, with no statistically significant difference between
      the various tests. In the 28 patients with no evidence of a subcutaneous Achilles
      tendon tear on imaging, the tests showed a high capability to detect that the
      Achilles tendon was intact (gap palpation specificity, 0.89; calf squeeze test
      specificity, 0.93; Matles test specificity, 0.85). Whichever tests were
      performed, at least two of them were positive for a subcutaneous tear of the
      Achilles tendon in all patients in this study.

PMID- 9548123
TI  - The snowboarder's foot and ankle.
AB  - We undertook a prospective study to determine the type and distribution of foot
      and ankle snowboarding injuries. Reports of 3213 snowboarding injuries were
      collected from 12 Colorado ski resorts between 1988 and 1995. Of these, 491
      (15.3%) were ankle injuries and 58 (1.8%) were foot injuries. Ankle injuries
      included 216 (44%) fractures and 255 (52%) sprains. Thirty-three (57%) of the
      foot injuries were fractures and 16 (28%) were sprains. The remaining injuries
      were soft tissue injuries, contusions, or abrasions. There was no significant
      correlation between boot type (soft, hybrid, or hard) and overall foot or ankle
      injury rate. There were significantly fewer ankle sprains in patients wearing
      hybrid boots and fewer fractures of the lateral process of the talus in patients
      wearing soft boots. An unexpectedly high number of fractures of the lateral
      process of the talus were noted. These 74 fractures represented 2.3% of all
      snowboarding injuries, 15% of all ankle injuries, and 34% of the ankle fractures.
      Many of these fractures are not visible on plain radiographs and require computed
      tomography imaging to be diagnosed. Diagnosis of this fracture pattern is
      paramount; the physician should be very suspicious of anterolateral ankle pain in
      the snowboarder, where subtle fractures that may require surgical intervention
      can be confused with anterior talofibular ligament sprains.

PMID- 9548124
TI  - Meniscal repair in the goat model. The use of healing adjuncts on central tears
      and the role of magnetic resonance arthrography in repair evaluation.
AB  - We evaluated the effect of adjunctive healing measures on central tears of the
      adult goat medial meniscus and the role of magnetic resonance arthrography in the
      assessment of menisci that have undergone a repair. Peripheral tears were made
      unilaterally in the medial menisci of seven goats in Group I and repaired with
      nonabsorbable suture. Six Group II goats had central medial meniscal tears
      repaired as in Group I plus an exogenous fibrin clot. Eight Group III goats had
      central tears plus abrasion of the parameniscal synovium and tear edges. Six
      months after surgery, a magnetic resonance imaging scan and a magnetic resonance
      arthrogram were obtained and the menisci were examined grossly. Group I goats
      showed healing in all seven knees. Central tears repaired with a fibrin clot
      (Group II) showed healing in one of six knees (17%). Central tears repaired with
      abrasion (Group III) showed healing in seven of eight knees (87.5%). Magnetic
      resonance arthrography was 100% accurate in detecting the presence or absence of
      complete residual tears. This study supports the current trend of using
      adjunctive measures for repair of central tears. Furthermore, abrasion of the
      parameniscal synovium and the tear edges appears to be more effective than the
      use of an exogenous fibrin clot. Magnetic resonance arthrography is useful in the
      evaluation of menisci that have undergone repair.

PMID- 9548125
TI  - Three-dimensional knee joint kinetics during a golf swing. Influences of skill
      level and footwear.
AB  - This study characterized knee joint kinetics during a golf swing and determined
      the influence of shoe type and golfer skill on the peak knee joint loads.
      Thirteen golfers each hit a golf ball using a five iron under two footware
      conditions: spiked and spikeless golf shoes. Data from a video-based motion
      capture system and force plates were used to compute the knee joint kinetics.
      Mean peak forces and moments differed significantly between the lead and trail
      knees, but these peak loads were not significantly affected by shoe type. Only
      the lead knee flexion and internal rotation moments were significantly correlated
      to skill level. The magnitude of some of the peak loads at the knee during the
      golf swing approached those reached during activities prohibited until late-stage
      knee rehabilitation. We concluded the following: The type of shoe worn and the
      skill level of the golfer need not be considered in deciding time to return to
      golfing; however, the leg that is recovering from surgery or injury should be
      considered. The most stressful phase of the golf swing, relative to the knee, is
      the downswing. There is probably no "normal" swing; each golfer seems to possess
      consistent, characteristic, patterns of knee loading.

PMID- 9548126
TI  - Strength deficits related to distal biceps tendon rupture and repair. A case
      report.

PMID- 9548127
TI  - Radial artery thrombosis in a young athlete. A case report.

PMID- 9548128
TI  - Fracture of the proximal tibia after Fulkerson anteromedial tibial tubercle
      transfer. A report of four cases.

PMID- 9548129
TI  - Pitcher's periostitis. A case report.

PMID- 9548131
TI  - The role of the scapula in athletic shoulder function.
AB  - The exact role and the function of the scapula are misunderstood in many clinical
      situations. This lack of awareness often translates into incomplete evaluation
      and diagnosis of shoulder problems. In addition, scapular rehabilitation is often
      ignored. Recent research, however, has demonstrated a pivotal role for the
      scapula in shoulder function, shoulder injury, and shoulder rehabilitation. This
      knowledge will help the physician to provide more comprehensive care for the
      athlete. This "Current Concepts" review will address the anatomy of the scapula,
      the roles that the scapula plays in overhead throwing and serving activities, the
      normal biomechanics of the scapula, abnormal biomechanics and physiology of the
      scapula, how the scapula may function in injuries that occur around the shoulder,
      and treatment and rehabilitation of scapular problems.

PMID- 9548130
TI  - Articular cartilage repair.
AB  - Articular cartilage can tolerate a tremendous amount of intensive and repetitive
      physical stress. However, it manifests a striking inability to heal even the most
      minor injury. Both the remarkable functional characteristics and the healing
      limitations reflect the intricacies of its structure and biology. Cartilage is
      composed of chondrocytes embedded within an extracellular matrix of collagens,
      proteoglycans, and noncollagenous proteins. Together, these substances maintain
      the proper amount of water within the matrix, which confers its unique mechanical
      properties. The structure and composition of articular cartilage varies three
      dimensionally, according to its distance from the surface and in relation to the
      distance from the cells. The stringent structural and biological requirements
      imply that any tissue capable of successful repair or replacement of damaged
      articular cartilage should be similarly constituted. The response of cartilage to
      injury differs from that of other tissues because of its avascularity, the
      immobility of chondrocytes, and the limited ability of mature chondrocytes to
      proliferate and alter their synthetic patterns. Therapeutic efforts have focused
      on bringing in new cells capable of chondrogenesis, and facilitating access to
      the vascular system. This review presents the basic science background and
      clinical experience with many of these methods and information on synthetic
      implants and biological adhesives. Although there are many exciting avenues of
      study that warrant enthusiasm, many questions remain. These issues need to be
      addressed by careful basic science investigations and both short- and long-term
      clinical trials using controlled, prospective, randomized study design.

PMID- 9548133
TI  - Distal femoral shaft fracture: a complication of endoscopic anterior cruciate
      ligament reconstruction--a case report.

PMID- 9548132
TI  - A statistics primer. Correlation and regression analysis.

PMID- 9548134
TI  - Low-field magnetic resonance imaging of the canine stifle joint: normal anatomy.
AB  - Low-field magnetic resonance imaging (MRI) was performed on the stifle joints of
      four normal adult mongrel dogs using a 0.064 Tesla scanner. Markers were placed
      on each stifle joint to serve as reference points for comparing gross sections
      with the images. A T1-weighted sequence was used to image one stifle joint on
      each dog in the sagittal plane and the other stifle joint in the dorsal plane.
      The dogs were euthanized immediately following MRI and the stifle joints frozen
      intact. Each stifle joint was then embedded in paraffin, again frozen, and
      sectioned using the markers as reference points. On T1-weighted images, synovial
      fluid had low signal intensity (dark) compared to the infrapatellar fat pad which
      had a high signal intensity (bright). Articular cartilage was visualized as an
      intermediate bright signal and was separated from trabecular bone by a dark line
      representing subchondral bone. Menisci, fibrous joint capsule, and ligamentous
      structures appeared dark. In the true sagittal plane, the entire caudal cruciate
      ligament was often seen within one image slice. The patella was visualized as an
      intermediate bright signal (trabecular bone) surrounded by a low intensity signal
      (cortical bone). The trochlea and the intercondylar notch were difficult areas to
      analyze due to signal volume averaging of the curved surface of these areas and
      the presence of several types of tissues.

PMID- 9548137
TI  - Quantitative methods for indirect CT lymphography.
AB  - In this investigation, we applied quantitative CT methods to characterize
      contrast enhanced lymph nodes opacified using iodinated contrast media for
      indirect CT lymphography. Iodinated nanoparticles were injected into the buccal
      submucosa and SQ into the metatarsus and metacarpus of four normal swine (1.0-4.0
      ml/site, 76 mg I/ml). Attenuation (HU), volume (cm3), iodine concentration (mg
      I/cm3), total iodine uptake (mg I), contrast-to-noise ratio (CNR), and percent
      injected dose (%ID) were estimated in opacified inguinal, cervical and
      parotid/mandibular lymph nodes using manual image segmentation techniques on 24
      hour post-contrast CT images. Lymph node volumes estimated by multiple slice ROI
      analysis were compared with estimates obtained by post-excisional weight
      measurements. HU and iodine concentration increased 5-20 fold in opacified nodes
      (p < 0.01) and CNR increased more than four-fold (p < 0.001). %ID ranged between
      3.5 and 11.9% and did not appear dose related. ROI estimated lymph node volumes
      approximated volumes calculated from weight measurements. (R2 = 0.94, p <
      0.0001). We conclude that interstitially injected iodinated nanoparticles
      increase attenuation and conspicuity of targeted nodes on CT images. Quantitative
      methods could play an important clinical role in more accurate metastasis
      detection.

PMID- 9548135
TI  - Development of interactive patient-based multimedia computer programs in
      veterinary orthopedic radiology.
AB  - Three computerized multimedia programs on large and small animal veterinary
      orthopedic radiology were developed and implemented for the radiology curriculum
      as an alternative to traditional film-based laboratory learning. Programs
      utilized "hot words" (colored text words that displayed an overlaid image label
      that highlighted lesions) and interactive quizzes which responded appropriately
      to selected answers. "Hot words" helped students develop confidence in accurate
      lesion detection and the interactive quizzes transformed learning from a passive
      to an active process. Multiple examples were provided for reinforcement and
      concepts were incorporated from other clinical disciplines for curriculum
      integration. Programs were written using a presentation software program,
      Toolbook for DOS based platform, and contained radiographic images made by laser
      scanning digitization. Multiple students could simultaneously access the programs
      through a network server. These pilot programs were implemented successfully and
      computerized multimedia presentation proved to be well suited to teaching
      radiology. Development of the programs required attention to a number of
      hardware, software, time and cost factors.

PMID- 9548136
TI  - A prospective clinical trial comparing metrizamide and iohexol for equine
      myelography.
AB  - A prospective clinical trial comparing adverse postmyelographic effects and
      myelographic quality of metrizamide and iohexol was conducted. Using a
      predetermined, randomized assignment, 24 horses exhibiting neurologic signs were
      administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via
      cerebellomedullary puncture. Each horse was evaluated postmyelographically for
      adverse effects. Myelographic quality was assessed by a numerical scoring method.
      Adverse effects were observed more frequently with metrizamide (21) compared with
      iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting
      neurologic signs and prolonged anesthetic recovery were the most common
      complications after myelography. There was no difference in myelographic quality
      (p > 0.05). We conclude that iohexol is safer than metrizamide for equine
      myelography and that quality myelograms can be obtained with either contrast
      medium.

PMID- 9548138
TI  - Use of computed tomography to evaluate the intestinal tract of adult llamas.
AB  - In the llama, signs of colic are obscure and may be exhibited as persistent
      sternal recumbency and anorexia even in the presence of a surgical lesion.
      Diagnostic methods for evaluation of abdominal disorders are limited. As a
      result, surgical intervention may be prolonged and increase the risk of mortality
      and postoperative complications. The objective of this study was to determine the
      feasibility of computed tomography to evaluate the llama intestinal tract.
      Eighteen hours prior to the computed tomography scan, six llamas were given
      barium sulfate (15%) via an orogastric tube. Following induction of general
      anesthesia, the llamas were positioned in sternal recumbency, and 10 mm
      contiguous slices were obtained from the diaphragm to the tuber ischiadicum.
      Structures that were consistently identified included the first, second, and
      third compartments (C1, 2, and 3), small intestine, spiral colon, and ascending
      colon. C1 was easily identified in the cranial aspect of the abdomen due to its
      large size relative to the other compartments and characteristic saccules. C2 was
      located cranial, ventral, and to the right of C1, while C3 was visualized as a
      tubular structure to the right and ventral to C1 and C2, C3 was traced caudally
      until it turned dorsally and continued cranially to a dilated ampulla in the
      right cranial abdomen delineating the entrance to the small intestine. The spiral
      colon was identified consistently in the left ventral caudal abdomen. Structures
      that could not be conclusively identified included the cecum and mesenteric lymph
      nodes. Computed tomography allowed a consistent evaluation of the major
      intestinal structures associated with colic in the llama. Thus, computed
      tomography is a potentially valuable noninvasive diagnostic tool to effectively
      evaluate the abdominal cavity and differentiate medical from surgical lesions in
      the llama.

PMID- 9548139
TI  - Radiographic diagnosis: liver lobe entrapment and associated emphysematous
      hepatitis.

PMID- 9548140
TI  - Radiographic appearance of the navicular bone and distal interphalangeal joint
      and their relationship with ossification of the collateral cartilages of the
      distal phalanx in Finnhorse cadaver forefeet.
AB  - Radiographic findings in the navicular bone and distal interphalangeal joint as
      well as the ossification status of the collateral cartilages of the distal
      phalanx were evaluated in 100 Finnhorse cadaver forefeet. The most common shapes
      of the proximal articular margin of the navicular bone were convex and straight.
      Remodeling of the navicular bone was common, especially on the lateral extremity.
      No bony fragments were identified at the distal flexor margin even though this
      area appeared irregular in several feet. Several large, rounded or lollipop
      shaped synovial invaginations were identified in only six feet. The thickness of
      the flexor cortex varied considerably, and the corticomedullary junction was uni-
      or bilaterally indistinct in nine feet. The shape of the sagittal ridge of the
      flexor cortex was commonly flat but varied. It appeared locally irregular or
      indistinct in 17 feet, but changes elsewhere along the flexor cortex were rare.
      Osteophytosis on the dorsal and palmar margins of the distal interphalangeal
      joint and entheseophytosis on the dorsal aspect of the middle phalanx and on the
      extensor process of the distal phalanx were common. "Possibly significant"
      ossification of the collateral cartilages (high sidebones or separate centers of
      ossification) was present in 36 feet; all grades of ossification in the
      proximal/palmaroproximal direction as well as palmar ossification were seen. A
      statistically significant relationship was found between entheseophytosis on the
      proximal flexor margin of the navicular bone and "possibly significant"
      ossification. Osteophytosis on the palmarodistal margin of the middle phalanx was
      more common in feet with a relatively long distal phalanx, suggestive of palmar
      ossification. Radiographic changes in the navicular bone or in the distal
      interphalangeal joint did not otherwise appear to be associated with ossification
      of the collateral cartilages of the distal phalanx in Finnhorses.

PMID- 9548141
TI  - Computed tomographic evaluation of dinosaur egg shell integrity.
AB  - The purpose of this study was to determine whether computed tomography (CT) could
      be used to identify hatching holes in partially embedded dinosaur eggs. One
      Faveololithus and two Dendroolithus eggs were examined using a fourth generation
      CT scanner. The eggs were partially embedded in a fossilized sediment matrix,
      with the exposed portion of the shell appearing intact. In CT images of all three
      eggs, the shells appeared hyperdense relative to the matrix. Hatching holes were
      visible as large gaps in the embedded portion of the shell, with inwardly
      displaced shell fragments. It was concluded that CT is an effective technique for
      nondestructively assessing dinosaur egg shell integrity.

PMID- 9548142
TI  - Ultrasonography of the femoral artery in six normal horses and three horses with
      thrombosis.
AB  - Ultrasonography of the femoral artery in the horse, including color, power and
      spectral Doppler, provides morphologic and dynamic information. This paper
      describes the use of the techniques in six clinically normal horses and three
      with femoral artery thrombosis. Useful landmarks for orientation are the
      saphenous artery and the medial saphenous vein. The lateral circumflex femoral
      artery can not be visualized. Recognition of the genus descendens artery is
      complicated due to the presence of multiple distal caudal femoral arteries. The
      femoral artery feeds a high resistance bed. In normal horses the peak systolic
      velocity varies between 50-90 cm/sec. Echoic tissue in the femoral artery lumen
      with stenosis, occlusion and collateral blood flow formation are features
      encountered in the patients.

PMID- 9548144
TI  - Ultrasound corner: "pseudo-catheter-sleeve" sign in the jugular vein of a horse.

PMID- 9548143
TI  - Ultrasound-assisted diagnosis of renal dysplasia in a 3-month-old Quarter Horse
      colt.
AB  - A 3-month-old foal was presented for correction of bilateral angular limb
      deformities. Azotemia was detected as an incidental finding. Small, misshapened,
      hyperechoic kidneys with decreased corticomedullary demarcation were noted with
      ultrasonography. Additionally, the internal renal architecture was abnormal in
      that the intrarenal vessels and distant collecting system were not clearly seen
      in either kidney. Ultrasound-guided renal biopsy was suggestive of congenital
      renal dysplasia, which was later confirmed at necropsy. Clinical, sonographic,
      and pathologic features of equine renal dysplasia are discussed.

PMID- 9548145
TI  - Ultrasonographic diagnosis--radiolucent pulmonary foreign body.

PMID- 9548146
TI  - MRI case presented as part of the 1997 A.C.V.R. oral certification examination:
      computed tomography/magnetic resonance imaging elective.

PMID- 9548147
TI  - CT case presented as part of the 1997 A.C.V.R. oral certification examination:
      computed tomography/magnetic resonance imaging elective.

PMID- 9548148
TI  - Profiling assisted reproductive technology: outcomes and quality of infertility
      management.
AB  - OBJECTIVE: To critically appraise the content of the American Society for
      Reproductive Medicine (ASRM)/Society for Reproductive Technology (SART) Registry.
      DESIGN: English-language literature review. PATIENT(S): Women undergoing
      treatment with assisted reproductive technology (ART). INTERVENTION(S): Current
      ART treatments, including IVF, GIFT, zygote intrafollopian transfer (ZIFT),
      oocyte micromanipulation, and cryopreserved embryo transfers. MAIN OUTCOME
      MEASURE(S): Compliance with clinical practice guidelines, and casemix-adjusted
      rates of live delivery, clinical pregnancy, ectopic pregnancy, miscarriage, birth
      defects, implantation, fertilization, and retrieval. RESULT(S): Outcomes should
      be adjusted for variation in patient characteristics known to affect prognosis,
      including maternal age, the duration of infertility, the presumed cause(s) of
      infertility, the patient's prior history of treatment for infertility, and
      diethylstilbestrol exposure. Outcome rates should be reported using the patient
      as the denominator, as well as cycle, retrieval, and transfer. The statistical
      significance of observed differences in events rates should be indicated. Because
      widely accepted clinical practice guidelines related to performance of ART
      procedures are not available, compliance with practice guidelines cannot
      currently be assessed. CONCLUSION(S): Reports based on ASRM/SART Registry data
      can be enhanced by refined casemix adjustment, assessing outcome rates per
      patient, as well as per component of ART procedure, and by providing an
      indication of the statistical significance of observed differences in event
      rates. In addition, a critical appraisal of available evidence related to
      particular aspects of infertility management would help clarify the areas in
      which there is an evidentiary basis for formulation of practice guidelines, as
      well as topics requiring additional clinical research.

PMID- 9548149
TI  - Profiling assisted reproductive technology: the Society for Assisted Reproductive
      Technology registry and the rising costs of assisted reproductive technology.

PMID- 9548150
TI  - Impairment of the developmental potential of frozen-thawed human zygotes obtained
      after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To evaluate the effects of cryopreservation on the survival, cleavage,
      and morphology of embryos and on the implantation and embryonic loss rates of
      human zygotes obtained after ICSI compared with frozen-thawed zygotes obtained
      after traditional IVF. A further objective was to evaluate the same parameters in
      nonfrozen sibling ICSI and IVF zygotes and to compare them with corresponding
      frozen-thawed zygotes. DESIGN: Open, retrospective, comparative study. SETTING:
      University-associated assisted reproductive program. PATIENT(S): Couples with
      severe male factor infertility and couples undergoing IVF during the same period.
      INTERVENTION(S): A cohort of 408 ICSI zygotes and 299 IVF zygotes was frozen in
      1,2 propanediol and sucrose using a slow-freezing protocol. Both groups of
      zygotes were frozen at approximately the same time after microassisted or
      conventional insemination. One hundred and eighty-seven ICSI and 110 IVF frozen
      zygotes were rapidly thawed during 44 ICSI cycles and 24 IVF cycles. Zygotes that
      appeared to have survived were cultured for 24 hours, and most of these embryos
      that were morphologically normal were transferred into patients. MAIN OUTCOME
      MEASURE(S): Survival rate (morphologically intact after thawing), cleavage rate
      and morphology of embryos, implantation rate, and the incidence of embryonic
      losses. RESULT(S): Except for survival rates, for which both ICSI and IVF frozen
      thawed zygotes showed similar and relatively high values (87.7% and 89.1%), the
      outcomes of other parameters evaluated were significantly different. Thus, from a
      total of 128 ICSI and 68 IVF embryos transferred, 14 (10.9%) and 17 (25.0%)
      implanted in 44 ICSI and 24 IVF frozen-thawed cycles, respectively. This
      difference in implantation corresponded with the rate of cleavage and morphology
      of the replaced embryos; the embryos that developed from frozen-thawed IVF
      zygotes cleaved faster and were more regular compared to the frozen-thawed ICSI
      zygotes. The embryonic loss rate was 57.1% for cryopreserved ICSI zygotes and
      11.8% for IVF zygotes. On the other hand, no difference in cleavage pattern,
      embryo morphology, implantation, and embryonic loss rates was found between
      nonfrozen sibling ICSI and IVF zygotes. CONCLUSION(S): The zygotes arising from
      ICSI cycles survived cryopreservation at a rate similar to IVF zygotes, but their
      ability to implant and develop further was probably affected by the
      cryopreservation procedure. The timing of zygote freezing was considered to be
      the principal reason for the lower developmental potential of frozen-thawed ICSI
      zygotes in the present study.

PMID- 9548151
TI  - Evidence for a stimulatory role of follicle-stimulating hormone on the
      spermatogonial population in adult males.
AB  - OBJECTIVE: To evaluate the effects of treatment with FSH on seminal indices and
      on the seminiferous epithelium of oligozoospermic subjects with normal FSH plasma
      levels. DESIGN: Placebo-controlled, double-blind randomized study. SETTING:
      Academic setting. PATIENT(S): Ninety subjects with idiopathic oligozoospermia
      (sperm count of < 10 x 10(6)/mL) and normal plasma levels of FSH.
      INTERVENTION(S): Three months of treatment with FSH (60 patients) or placebo (30
      patients); bilateral testicular fine-needle aspiration. MAIN OUTCOME MEASURE(S):
      Seminal indices; testicular cytologic features; plasma levels of FSH, LH, and
      testosterone; and ultrasonographic testicular examination. RESULT(S): According
      to seminal indices, patients treated with FSH and placebo were classified as
      nonresponders or as responders (as determined by at least a doubling of sperm
      count). No placebo-treated patients responded to treatment. Among FSH-treated
      patients, 20 responded to hormonal treatment and 40 did not. The results of
      pretreatment cytologic examination of testicular specimens from patients who did
      not respond to FSH treatment were consistent with hypospermatogenesis associated
      with maturational disturbances at the spermatid level. In contrast, patients who
      responded to treatment with FSH had isolated hypospermatogenesis without
      maturational disturbances. After FSH therapy, we detected an increase of
      spermatogonia and spermatocyte population in both the responder and nonresponder
      subjects. This increase was associated with an activation of spermatogenic and
      spermiogenic processes and with a rise in ejaculated sperm concentration only
      when isolated hypospermatogenesis was present (responder patients).
      CONCLUSION(S): The findings of this study demonstrate that FSH treatment
      increases the spermatogonial population in men. This treatment may be appropriate
      for oligozoospermic subjects who have normal FSH plasma levels and a testicular
      evaluation characterized by hypospermatogenesis without maturational
      disturbances.

PMID- 9548152
TI  - Coculture of human sperm with bovine oviduct epithelial cells decreases sperm
      chromatin structural changes seen during culture in media alone.
AB  - OBJECTIVE: To compare sperm chromatin structural changes seen in media only
      culture or in coculture with bovine oviduct epithelial cells. DESIGN: Three
      freshly ejaculated and three cryopreserved sperm samples in media culture or in
      oviduct epithelial cell coculture. Sperm in each treatment were evaluated by the
      sperm chromatin structure assay during a 72-hour time course. SETTING: An
      academic research laboratory. PATIENT(S): Normospermic donors with children.
      INTERVENTION(S): Semen collection through masturbation after 48 hours of
      abstinence. MAIN OUTCOME MEASURE(S): The sperm chromatin structure assay using
      flow cytometry to detect the susceptibility of sperm in either treatment to
      denaturation of DNA in situ. RESULT(S): The sperm chromatin structure assay data
      differed for sperm type (fresh or cryopreserved), over time, and between
      treatments within 6 hours of culture. In oviduct epithelial cell coculture, fresh
      sperm chromatin structure assay values for fresh sperm were stable, whereas in
      control medium higher chromatin degeneration levels were seen by 10 hours. For
      cryopreserved sperm, chromatin degeneration had increased by 1 hour postthaw in
      both treatments, although levels were higher in the control treatment thereafter.
      CONCLUSION(S): Sperm chromatin structural changes occur over time in culture.
      Such changes were observed within 2 hours for cryopreserved sperm. Coculture of
      sperm with oviduct epithelial cells results in a stabilizing effect for sperm
      against chromatin changes.

PMID- 9548153
TI  - Maximizing pregnancy rates and limiting higher-order multiple conceptions by
      determining the optimal number of embryos to transfer based on quality.
AB  - OBJECTIVE: To define statistical thresholds for the number of embryos to be
      transferred to achieve an optimal pregnancy rate and keep higher-order multiple
      conceptions (pregnancy with more than two fetal sacs with cardiac activity)
      within an acceptable limit. DESIGN: A retrospective review of patient records.
      SETTING: Private practice assisted reproductive technology (ART) facility.
      PATIENT(S): Seven hundred fifty-four consecutive patients who underwent IVF-ET
      from 1994-1996. INTERVENTION(S): Embryo grading and score system used on day 3 of
      embryo transfer. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and multiple
      conception rates. RESULT(S): For women < or =35 years old, transfer of up to four
      poor-quality, two fair-quality, or two good-quality embryos is optimal to
      eliminate any risk of higher-order multiple pregnancies. Transfer of four poor
      quality, three fair-quality, or two good-quality embryos is recommended for women
      36 to 39 years old. In women who are > or =40 years old, five embryos need to be
      transferred regardless of embryo quality. CONCLUSION(S): The mean cumulative
      embryo score can be used as a reference to determine an optimal number of embryos
      to transfer and to predict pregnancy outcome.

PMID- 9548154
TI  - The performance of subcutaneously injected Fertinex when used as the sole
      gonadotropin for in vitro fertilization stimulation.
AB  - OBJECTIVE: To assess the performance of Fertinex (urofollitropin; Serono
      Laboratories, Norwell, MA) in stimulating the development of multiple follicles
      and initiating subsequent pregnancy in patients undergoing controlled ovarian
      hyperstimulation (COH) for IVF. DESIGN: Prospective observational study. SETTING:
      Private assisted reproductive technology (ART) center. PATIENT(S): Ninety-three
      women who underwent an IVF cycle of COH in which Fertinex was used as the sole
      gonadotropin. INTERVENTION(S): The COH protocol included Fertinex with leuprolide
      acetate down-regulation in the late luteal phase or the early follicular phase.
      Embryo transfer was performed after 3 days of culture. MAIN OUTCOME MEASURE(S):
      Stimulation parameters, embryologic data, and pregnancy rates (PRs). RESULT(S):
      Ninety-three patients underwent 97 cycles of COH, with a cancellation rate of
      13.4%. The clinical PR was 42% per initiation, 49% per retrieval, and 51% per
      transfer. Shorter stimulation periods, lower estradiol levels either per follicle
      punctured or per oocyte retrieved, and slower embryo development were observed.
      Patients responded to Fertinex in three distinct stimulation patterns: escalating
      response with a peak estradiol level of < or =3,000 pg/mL, escalating response
      with a peak estradiol level of >3,000 pg/mL, or escalating response characterized
      by a drop in the estradiol level or a plateau before hCG administration. All
      three responses had similar PRs. CONCLUSION(S): Fertinex can be used successfully
      as the sole gonadotropin for COH in ART without compromising high PRs.
      Traditional estradiol response curves or cancellation criteria may not apply when
      Fertinex is used as the sole gonadotropin for COH in ART.

PMID- 9548155
TI  - Recruitment of follicles by recombinant human follicle-stimulating hormone
      commencing in the luteal phase of the ovarian cycle.
AB  - OBJECTIVE: To investigate, in patients who previously had a suboptimal ovarian
      stimulation cycle, the benefit of starting ovarian stimulation before the onset
      of menses. DESIGN: Prospective, randomized, controlled study. SETTING: A tertiary
      referral center for infertility treatment. PATIENT(S): Forty patients undergoing
      IVF or GIFT from whom only 3-6 oocytes were retrieved in their last cycle.
      INTERVENTION(S): Recombinant human FSH was administered before the onset of the
      menstrual period (experimental group) or in the early follicular phase after the
      onset of menses (control group). MAIN OUTCOME MEASURE(S): The number of oocytes
      retrieved. RESULT(S): Patients in the experimental group were ready for oocyte
      retrieval on menstrual cycle day 11 instead of cycle day 14. The number of
      oocytes retrieved was not significantly different between the two groups.
      CONCLUSION(S): Poor responders do not benefit from commencing recombinant human
      FSH therapy in the luteal phase.

PMID- 9548156
TI  - Gestational carrier pregnancy.
AB  - OBJECTIVE: To evaluate the results of a gestational carrier program in terms of
      pregnancy rates in fresh and cryopreserved cycles. DESIGN: Retrospective
      analysis. SETTING: Private IVF program. PATIENT(S): Women with uterine or medical
      reasons for unsuccessful gestation. INTERVENTION(S): In vitro fertilization of
      oocytes with fresh or cryopreserved ET to gestational carriers. MAIN OUTCOME
      MEASURE(S): Pregnancy rates and deliveries. RESULT(S): A PR of 56.3% and a cycle
      rate of 30.8% was achieved in each patient <40 years of age in 117 cycles of
      fresh or cryopreserved ET. There were no pregnancies for nine patients >40 years
      of age in 27 cycles. CONCLUSION(S): Carrier gestation offers a satisfactory
      solution to childlessness caused by uterine or major medical factors.

PMID- 9548157
TI  - First pregnancies after preconception diagnosis of translocations of maternal
      origin.
AB  - OBJECTIVE: To develop an approach to preimplantation diagnosis of translocations
      that would not require the use of specific DNA probes for each translocation
      type. DESIGN: Retrospective analysis. SETTING: Clinic. PATIENT(S): Two patients
      with 45XX,der(13;14)(q10;q10) karyotypes and one patient with a
      46XX,t(4;14)(p15;q24) karyotype. INTERVENTION(S): Based on the observation that
      first polar body chromosomes remain at the metaphase stage for a few hours after
      oocyte retrieval, fluorescence in situ hybridization with chromosome-painting
      probes was used to perform preconception genetic diagnosis of translocation of
      maternal origin. MAIN OUTCOME MEASURE(S): Oocyte FISH analysis. RESULT(S): A
      total of 31 mature oocytes were produced, and results were obtained in 23 first
      polar bodies. After IVF-ET, all three patients became pregnant, preconception
      diagnoses being confirmed by prenatal diagnosis or birth. CONCLUSION(S):
      Preconception diagnosis of translocations may reduce significantly the risk of
      chromosomally unbalanced offspring and pregnancy loss. This method is simpler
      than previous approaches because the need to develop specific DNA probes for each
      translocation type is avoided.

PMID- 9548159
TI  - Metformin therapy improves the menstrual pattern with minimal endocrine and
      metabolic effects in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine the clinical, hormonal, and biochemical effects of 4-6
      months of metformin therapy in obese patients with polycystic ovary syndrome
      (PCOS). DESIGN: Prospective study. SETTING: The Gynecological Endocrine Unit of
      University Central Hospital, Oulu, Finland. PATIENT(S): Twenty obese patients
      with PCOS. INTERVENTION(S): Patients were treated with 0.5 g of metformin three
      times daily for 4-6 months. MAIN OUTCOME MEASURE(S): Clinical symptoms, menstrual
      pattern, and hirsutism, as well as serum concentrations of sex steroids, sex
      hormone-binding globulin (SHBG), gonadotropins, and lipids were assessed during
      the treatment. RESULT(S): Eleven women (68.8% of the women with menstrual
      disturbances) experienced more regular cycles during therapy. No changes in
      hirsutism, body mass index, or blood pressure occurred. The mean testosterone
      level was decreased significantly after 2 months of treatment but returned to the
      starting level by 4-6 months. Free testosterone levels decreased significantly
      during the treatment. There was no significant change in the levels of other sex
      steroids or lipids measured at 4-6 months of treatment. CONCLUSION(S): Metformin
      therapy is well tolerated by the majority of patients and may be clinically
      useful, especially in obese patients with PCOS and menstrual disturbances.

PMID- 9548158
TI  - Serum androgen levels in women who have recurrent miscarriages and their
      correlation with markers of endometrial function.
AB  - OBJECTIVE: To compare plasma androgen concentrations in women who have recurrent
      miscarriages and in fertile women, and to correlate the results with
      concentrations of the endometrial protein PP14 in uterine flushings and plasma
      from women who have recurrent miscarriages. DESIGN: Retrospective study. SETTING:
      Hospital research unit. PATIENT(S): Women attending a recurrent miscarriage
      clinic and normal fertile volunteers. Ten of the women with recurrent
      miscarriages had polycystic ovary disease (PCOD) as assessed by ultrasonography
      or increased follicular LH levels. INTERVENTION(S): Plasma samples were obtained
      from the women on days LH-7, LH-4, LH+0, and LH+7 or LH+10 of a cycle. An
      endometrial flushing sample and a biopsy specimen were taken from women with
      recurrent miscarriages on day LH+7 or LH+10. MAIN OUTCOME MEASURE(S):
      Androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were
      measured in the plasma samples. The endometrial protein PP14 was measured in the
      uterine flushings and in the LH+7 or LH+10 plasma samples from the women with
      recurrent miscarriages. RESULT(S): Testosterone concentrations were higher in the
      women with recurrent miscarriages both with and without PCOD on days LH-7 and LH
      4 of the cycle. Concentrations of androstenedione also were higher in the women
      with recurrent miscarriages, but without PCOD on day LH-7. Testosterone SHBG
      ratios were higher in the women with recurrent miscarriages, without PCOD
      compared with the controls on days LH-7, LH+0, and LH+7. Mean follicular
      testosterone concentrations were correlated negatively with both uterine (r = 
      0.47) and plasma (r = -0.49) PP14 levels on day LH+10. Mean luteal phase
      testosterone SHBG ratios were correlated negatively with uterine PP14
      concentrations on day LH+7 of the cycle (r = -0.674). CONCLUSION(S): Androgen
      levels are higher in women who have recurrent miscarriages than in normal fertile
      controls. These high levels of androgens may have a detrimental effect on
      endometrial function.

PMID- 9548160
TI  - Late endocrine effects of ovarian electrocautery in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To examine the duration of the changes in endocrine indices produced
      by ovarian electrocautery in women with polycystic ovary syndrome (PCOS). DESIGN:
      Long-term observational study. SETTING: University hospital. PATIENT(S):
      Infertile women with PCOS. INTERVENTION(S): Ovarian electrocautery was performed
      through the laparoscope. Blood was sampled before the operation and at defined
      intervals thereafter. After the establishment of regular cycles, sampling was
      performed 1 week before the menstrual period. MAIN OUTCOME MEASURE(S): The
      patients were observed before and at defined intervals for up to 20 years after
      ovarian electrocautery. Serum concentrations of hypophyseal and ovarian hormones
      were determined, including sex hormone-binding globulin (SHBG). RESULT(S): There
      was a clear shift from anovulation to ovulatory cycles and a significant decrease
      in androgens and gonadotropins. The concentration of SHBG increased. These
      effects lasted for many years; after 18-20 years, two thirds of the women were
      still ovulating. CONCLUSION(S): Ovarian electrocautery for PCOS normalizes
      ovarian function, including androgen production, and the results seem to be
      stable for 18-20 years.

PMID- 9548161
TI  - Effects of triptorelin versus placebo on the symptoms of endometriosis.
AB  - OBJECTIVE: To compare the effect of a GnRH-agonist, triptorelin, versus placebo
      on the symptoms of endometriosis. DESIGN: A prospective, randomized, double-blind
      study of 6 months of treatment followed by 12 months of follow-up. SETTING:
      Departments of Obstetrics and Gynecology at two universities and one general
      hospital. PATIENT(S): Forty-nine women with symptoms of laparoscopically verified
      endometriosis. INTERVENTION(S): Triptorelin depot or placebo was given every 4
      weeks. Clinical evaluation, including the Duration Intensity Behavior Scale and
      Visual Analogue Scale for pain, was performed before the injections and up to 12
      months after treatment. A control laparoscopy was performed 4-6 weeks after the
      last injection. MAIN OUTCOME MEASURE(S): Quantitation of pain. RESULT(S): Twenty
      four patients had active treatment and 25 received placebo. Pain symptoms
      according to both scales were significantly more reduced after 2 months of
      triptorelin treatment compared to placebo. The extent of endometriotic lesions
      was reduced 50% during triptorelin treatment and increased 17% during placebo.
      The average area of endometriotic lesions was reduced 45% during triptorelin
      treatment but was unchanged during placebo. Side effects, mainly hot flushes,
      were experienced by 80% of the actively treated group but also by 33% of patients
      in the placebo group. Because of recurrent symptoms, only five patients could be
      observed for 12 months after completion of treatment. CONCLUSION(S): Triptorelin
      reduces endometriotic lesions and pain to a significantly higher degree than
      placebo.

PMID- 9548162
TI  - Treatment of severe postmenopausal endometriosis with an aromatase inhibitor.
AB  - OBJECTIVE: To treat an unusually aggressive case of recurrent postmenopausal
      endometriosis. DESIGN: Case report. SETTING: University of Texas Southwestern
      Medical Center (Dallas, Texas). PATIENT(S): A 57-year-old woman who presented
      with recurrent severe endometriosis after hysterectomy and bilateral salpingo
      oophorectomy. INTERVENTION(S): Oral administration of anastrozole (an aromatase
      inhibitor) (1 mg/d) and elemental calcium (1.5 g/d) for 9 months. Alendronate (a
      nonestrogenic inhibitor of bone resorption), 10 mg/d, was added to this regimen.
      MAIN OUTCOME MEASURE(S): Reduction in size of endometriotic lesion, pain relief,
      tissue levels of aromatase P450 messenger RNA, bone density. RESULT(S):
      Circulating levels of estradiol-17beta were reduced to approximately 50% of the
      baseline value after the onset of treatment with anastrozole. Pain rapidly
      decreased and completely disappeared after the 2nd month of treatment. The 30 x
      30 x 20-mm bright red polypoid vaginal lesion was reduced to a 3-mm gray tissue
      by the end of 9 months of treatment. Markedly high pretreatment levels of
      aromatase P450 messenger RNA in the endometriotic tissue became undetectable in a
      specimen obtained from a repeated biopsy after 6 months of treatment. Bone
      density of lumbar spine decreased by 6.2% after 9 months of treatment.
      CONCLUSION(S): This is the first description of the use of an aromatase inhibitor
      in the treatment of endometriosis. The short-term results were extraordinarily
      successful in elimination of pain and near-complete eradication of implants
      associated with severe endometriosis not responsive to other therapy. We conclude
      that the recently developed potent aromatase inhibitors are candidate drugs in
      the treatment of endometriosis that is resistant to standard regimens.

PMID- 9548163
TI  - Ovarian function during the use of a single contraceptive implant: Implanon
      compared with Norplant.
AB  - OBJECTIVE: To study the mechanism of action of Implanon, a single-rod
      contraceptive implant containing etonogestrel, in healthy women during 3 years.
      DESIGN: Prospective, randomized comparison with Norplant. The study was conducted
      for 2 years in Sweden but was extended to 3 years in Finland. SETTING: Two
      outpatient clinics. PATIENT(S): Thirty-two healthy women who were between 18 and
      40 years of age with normal ovulatory cycles. Seven women receiving Implanon and
      three receiving Norplant participated in the third year. INTERVENTION(S): On or
      between days 1 and 5 of a spontaneous menstrual cycle, the subjects received
      either the etonogestrel-containing implant (Implanon) or the levonorgestrel
      containing implant (Norplant). MAIN OUTCOME MEASURE(S): Ultrasonography was
      performed and/or progesterone concentrations were determined to confirm ovulation
      in a control cycle. Follicular development, endometrial thickness, and serum
      concentrations of 17beta-estradiol and progesterone were assessed twice per week
      during 4-week periods at regular intervals and after implant removal for 6 weeks
      to monitor return of ovulation. Times required to remove the respective implants
      were evaluated, as were possible complications. RESULT(S): Seven women who
      received Implanon and three who received Norplant completed 3 years of study.
      There were no pregnancies. Ovulation was observed for the first time with
      Norplant after 18 months. The first ovulation with Implanon was observed after 30
      months. Mean endometrial thickness was <4 mm during treatment with Implanon from
      month 12 onward. The mean (+/-SD) time to remove Implanon was 5.9 +/- 3.4
      minutes. The mean (+/-SD) time to remove Norplant was 17.9 +/- 9.9 minutes.
      Ovulation resumed promptly after the use of either implant. CONCLUSION(S):
      Results from this study provide convincing evidence of 3-year contraceptive
      efficacy with Implanon, mainly by ovulation inhibition.

PMID- 9548164
TI  - Preparation by differential gradient centrifugation is better than swim-up in
      selecting sperm with normal morphology (strict criteria).
AB  - OBJECTIVE: To evaluate two commonly used methods of sperm preparation with
      respect to their effects on sperm morphology (strict criteria). DESIGN: Auto
      controlled, split sample study performed on the semen of 74 male partners of
      couples enrolled for IVF. SETTING: In vitro fertilization and andrology
      laboratories at a tertiary care, major teaching hospital. PATIENT(S): Seventy
      four male partners of couples who were scheduled to undergo IVF. INTERVENTION(S):
      Equal halves of the same semen sample were evaluated for strict criteria sperm
      morphology before and after preparation by differential gradient centrifugation
      using Percoll (Pacific Andrology, Montrose, CA) and by the standard swim-up
      method. MAIN OUTCOME MEASURE(S): The percentage of morphologically normal sperm
      was assessed using strict criteria before and after the two methods of sperm
      preparation. Specific parameters studied were individual abnormalities of the
      head, midpiece, and tail. RESULT(S): Sperm preparation using differential
      gradient centrifugation with Percoll produced a significantly greater number of
      specimens with normal sperm morphology and also showed higher absolute
      quantitative improvement over the swim-up method. The two methods were comparable
      in regard to their effects on specific sperm abnormalities (i.e., head, midpiece,
      and tail defects). CONCLUSION(S): The differential gradient sperm separation
      method using Percoll is superior to the swim-up method for selecting sperm with
      normal morphology as assessed by strict criteria. Because sperm morphology as
      assessed by strict criteria is a good predictor of oocyte fertilization, this
      method can be recommended as the method of choice for assisted reproductive
      technology laboratories. Use of this method may help improve outcome by
      increasing fertilization rates.

PMID- 9548165
TI  - Creatine kinase activity in human spermatozoa and seminal plasma lacks predictive
      value for male fertility in in vitro fertilization.
AB  - OBJECTIVE: To examine the predictive value of creatine kinase in human
      spermatozoa and seminal plasma from patients treated in an IVF program. DESIGN:
      Prospective, blind clinical study. SETTING: Male infertility clinic. PATIENT(S):
      Seventy-three patients and 32 fathers (age, <45 years). INTERVENTION(S):
      Determination of creatine kinase activity in seminal plasma, washed spermatozoa,
      and swim-up purified spermatozoa from patients treated in an IVF program. MAIN
      OUTCOME MEASURE(S): Creatine kinase activity in seminal plasma, washed
      spermatozoa, and swim-up purified spermatozoa. RESULT(S): Creatine kinase
      activity in washed spermatozoa correlated significantly with normal sperm
      morphology. No significant correlations were found between creatine kinase
      activity or creatine kinase isoenzyme ratio in seminal plasma, washed
      spermatozoa, or swim-up purified spermatozoa and success in the IVF program. The
      percentage of spermatozoa with normal morphology was significantly lower in
      patients whose sperm did not fertilize than in patients whose sperm did fertilize
      oocytes and in the control group of proven fathers. CONCLUSION(S): Total creatine
      kinase activity and creatine kinase isoenzyme distribution are not sperm function
      markers for prediction of male fertility in IVF treatment.

PMID- 9548166
TI  - Alpha-glycosidase activity in seminal plasma: predictive value for outcome in
      intrauterine insemination and in vitro fertilization.
AB  - OBJECTIVE: To test the hypothesis that alpha-glycosidase activity in seminal
      plasma can predict the outcome of both IUI and IVF. DESIGN: A retrospective
      cohort study. SETTING: Tertiary fertility center in a university hospital.
      PATIENT(S): Eighty-three subfertile couples who underwent IUI and 125 subfertile
      couples who underwent IVF. INTERVENTION: None. MAIN OUTCOME MEASURE(S):
      Determination of the alpha-glycosidase activity in seminal plasma before an IUI
      or IVF attempt, correlation of alpha-glycosidase activity and other semen
      parameters, and prediction of pregnancy using alpha-glycosidase activity in
      seminal plasma. RESULT(S): Alpha-glycosidase activity correlated with sperm
      count. In the IUI group, alpha-glycosidase activity of >23.9 mU/mL predicted
      pregnancy with a sensitivity of 100% and a specificity of 55.2%. In the IVF
      group, the outcome could not be predicted with use of any of the semen
      parameters. CONCLUSION(S): Alpha-glycosidase activity measured in mU/mL probably
      can be used as a predictor for IVF and pregnancy in an IUI program but has no
      predictive value with regard to pregnancy rate in an IVF program.

PMID- 9548167
TI  - Simultaneous assessment of sperm chromatin condensation and morphology before and
      after separation procedures: effect on the clinical outcome after in vitro
      fertilization.
AB  - OBJECTIVE: To look for correlations between acridine orange (AO) staining and
      semen parameters before and after sperm separation procedures and to assess
      whether the AO test predicts fertilization or pregnancy outcomes after standard
      IVF and intracytoplasmic sperm injection. DESIGN: Prospective study that
      simultaneously assesses sperm morphology and nuclear protein maturity on a cell
      by-cell basis before and after preparative procedures. SETTING: University
      teaching hospital. PATIENT(S): Men (n = 140) undergoing diagnostic semen
      analysis. MAIN OUTCOME MEASURE(S): Acridine orange fluorescence of sperm nuclei,
      semen parameters, IVF outcome. RESULT(S): In unprocessed samples, 90% of sperm
      with normal heads displayed green fluorescence (mature nuclear protein);
      significantly lower percentages of green fluorescence were observed in sperm with
      abnormal heads. The percentage of mature normal sperm in the specimen correlated
      with motility. Sperm maturity after swim-up or Percoll gradient was significantly
      improved for sperm with normal or abnormal heads. The percentage of mature normal
      sperm correlated with motility after either Percoll or swim-up. Neither the
      percentages of mature nuclei nor mature normal nuclei correlated with
      fertilization or pregnancy outcome. CONCLUSION(S): Nuclear protein maturation
      correlates with sperm motility and morphology. Because morphologically normal and
      motile sperm are more mature, separation procedures should generate a population
      of sperm with the highest fertilization capacity. Acridine orange staining,
      however, did not predict fertilization efficiency or pregnancy outcome in IVF
      cycles.

PMID- 9548169
TI  - Detection of P2 precursors in the sperm cells of infertile patients who have
      reduced protamine P2 levels.
AB  - OBJECTIVE: To determine whether the reduction in the protamine P2 content
      (increased P1/P2 ratio) reported in some infertile patients could result from
      incomplete processing of protamine P2 precursors. DESIGN: Analysis of samples
      with a marked reduction in the protamine P2 content using polyacrylamide gel
      electrophoresis and subsequent detection of protamine P2 precursors through
      Western blot analysis. SETTING: University departments and laboratories.
      PATIENT(S): One hundred eighty-four men undergoing an evaluation for infertility.
      MAIN OUTCOME MEASURE(S): Comparative Western blot analysis of nuclear sperm
      proteins using specific antibodies to protamine P1 and protamine P2. RESULT(S):
      After selection of the samples with a marked reduction of the protamine P2
      content and subsequent analysis by Western blot, a small proportion of putative
      P2 precursors was detected in most samples, whereas a significant increase was
      detected in two of them. CONCLUSION(S): In some infertile men, a reduction in the
      protamine P2 content relative to protamine P1 (increased P1/P2 ratio) is detected
      concomitant with an increase in the amount of putative P2 precursors. This could
      represent the first report of incomplete processing of a nuclear sperm protein in
      humans.

PMID- 9548168
TI  - Increase of intracellular calcium is not a cause of pentoxifylline-induced
      hyperactivated motility or acrosome reaction in human sperm.
AB  - OBJECTIVE: To investigate the effects of the phosphodiesterase inhibitor
      pentoxifylline on hyperactivated motility and acrosome reaction in human sperm
      and to determine whether its stimulatory effects occur via increased
      intracellular calcium levels. DESIGN: Prospective study. SETTING: Academic
      tertiary care facility. PARTICIPANT(S): Healthy male donors. INTERVENTION(S): The
      effects of pentoxifylline on hyperactivated motility, acrosome reaction, and
      intracellular calcium were studied and compared with the effects of progesterone.
      Thapsigargin, a known mobilizer of intracellular calcium, also was used as
      positive control. MAIN OUTCOME MEASURE(S): Hyperactivated motility was assessed
      by computer-assisted sperm motion analysis using the HTM-IVOS, acrosome reaction
      was evaluated with the fluorescent probe fluorescein isothiocyanate-labeled Pisum
      sativum agglutinin, and intracellular calcium was determined by fura-2 using
      spectrofluorometry. RESULT(S): Pentoxifylline significantly increased both
      hyperactivated motility and acrosome reaction. Enhancement of hyperactivated
      motility by pentoxifylline in the capacitation medium persisted for up to 5 hours
      after pentoxifylline was washed from the medium. It also enhanced the percentage
      of acrosome-reacted spermatozoa after 4 hours of incubation. These effects
      occurred in the presence of a marginally significant decrease in intracellular
      calcium. CONCLUSION(S): Pentoxifylline stimulates hyperactivated motility and
      acrosome reaction in spermatozoa from fertile men. Its stimulatory effects occur
      through mechanism(s) other than increase in intracellular calcium.

PMID- 9548170
TI  - Characterization of tubal and decidual leukocyte populations in ectopic
      pregnancy: evidence that endometrial granulated lymphocytes are absent from the
      tubal implantation site.
AB  - OBJECTIVE: To compare and quantify leukocyte populations at the tubal
      implantation site, in the tubal mucosa away from the implantation site and in the
      intrauterine decidua in women who have had an ectopic tubal pregnancy with
      leukocyte populations in the decidualized endometrium in women who have had a
      normal intrauterine pregnancy. DESIGN: Retrospective immunohistochemical study.
      SETTING: Department of Pathology, University of Newcastle, Royal Victoria
      Infirmary, Newcastle upon Tyne, Tyne and Wear, United Kingdom. PATIENT(S):
      Paraffin-embedded tissue blocks from 30 women who had had an ectopic pregnancy
      (EP) and control tissue blocks from 19 women who had undergone elective first
      trimester pregnancy termination. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Quantitative analysis of defined leukocyte subpopulations in the fallopian tube
      (at the implantation site and in the tubal mucosa away from the implantation
      site) and intrauterine decidua. RESULT(S): Endometrial granulated lymphocytes
      were absent from both the tubal mucosa away from the implantation site and the
      tubal implantation site. T lymphocytes and macrophages formed the predominant
      leukocyte subpopulations in both tubal areas. In the intrauterine decidua from
      women who had had an EP, endometrial granulated lymphocytes were the most
      abundant leukocyte population and macrophages and T cells formed the second and
      third major leukocyte subpopulations, respectively. No differences were detected
      in the number or proportion of these decidual leukocytes in women who had had a
      normal pregnancy vs. in those who had had an EP. CONCLUSION(S): The absence of
      endometrial granulated lymphocytes from the tubal implantation site suggests that
      the local presence of the cells is not essential for implantation and early
      placental development events.

PMID- 9548171
TI  - Assessment of a tablet drug delivery system incorporating nonoxynol-9
      coprecipitated with polyvinylpyrrolidone in preventing the onset of pregnancy in
      rabbits.
AB  - OBJECTIVE: To assess the in vivo efficacy of the tablet drug delivery system
      containing nonoxynol-9 coprecipitated with polyvinylpyrrolidone by delivering the
      spermicidal agents vaginally and evaluating their ability to prevent the onset of
      pregnancy in rabbits. DESIGN: Controlled clinical study. SETTING: Division of
      Laboratory and Animal Resources, College of Pharmacy, University of Kentucky.
      ANIMAL(S): Forty-two New Zealand White female rabbits. INTERVENTION(S): The
      rabbits were artificially inseminated at various intervals after vaginal
      insertion of the tablet drug delivery system containing either
      polyvinylpyrrolidone only (0 minutes) or nonoxynol-9 coprecipitated with
      polyvinylpyrrolidone (polyvinylpyrrolidone/nonoxynol-9; 0, 3, 30, 180, and 360
      minutes). The rabbits were induced to ovulate 6 hours before insemination by i.m.
      injection of hCG (200 IU). MAIN OUTCOME MEASURE(S): The onset of pregnancy in the
      rabbits was evaluated after insertion of the tablet drug delivery system
      containing polyvinylpyrrolidone only or polyvinylpyrrolidone/nonoxynol-9 at
      various intervals, followed by artificial insemination. RESULT(S): The onset of
      pregnancy was not reduced significantly when the tablet drug delivery system
      containing polyvinylpyrrolidone or polyvinylpyrrolidone/nonoxynol-9 was used and
      insemination was performed immediately after tablet insertion (time 0). However,
      pregnancy rates (PRs) were reduced significantly in the rabbits that received the
      tablet drug delivery system containing polyvinylpyrrolidone/nonoxynol-9 and were
      inseminated at 3, 30, 180, and 360 minutes after tablet insertion. The highest PR
      reduction occurred between 30 and 180 minutes after insertion of the tablet drug
      delivery system containing polyvinylpyrrolidone/nonoxynol-9. CONCLUSION(S): The
      tablet drug delivery system is an efficient method of delivering the tested
      spermicidal agents vaginally. The design and dosage used in preparing the tablet
      drug delivery system provide short- and long-term release of the spermicidal
      agents, which results in almost immediate and extended enhancement of their
      contraceptive properties.

PMID- 9548172
TI  - Soluble intercellular adhesion molecule-1 in ovarian follicles: production by
      granulosa luteal cells and levels in follicular fluid.
AB  - OBJECTIVE: To determine the concentration of the soluble form of intercellular
      adhesion molecule (ICAM)-1 in granulosa luteal cell-conditioned media and in
      follicular fluid (FF). DESIGN: Granulosa cells and FF samples were obtained at
      the time of oocyte retrieval for IVF. In 10 women, a total of 33 fluids were
      obtained from individual follicles, whereas in 70 women, the follicular aspirates
      were pooled. SETTING: Clinica "L. Mangiagalli" and Reproductive Center, San
      Raffaele Hospital, Milan, Italy. PATIENT(S): Eighty women referred for IVF for
      tubal factor or male factor infertility. INTERVENTION(S): Women underwent ovarian
      hyperstimulation. MAIN OUTCOME MEASURE(S): Soluble ICAM-1 was measured by an
      ELISA, and its levels were correlated with follicular size, the number of
      retrieved oocytes, and the number of follicles with a diameter of >15 mm.
      RESULT(S): The concentration of soluble ICAM-1 in granulosa luteal cell
      conditioned media was 17.8 +/- 1.8 ng/5 x 10(5) cells. Interleukin-1beta can
      stimulate soluble ICAM-1 release in a dose-dependent manner. A significant
      positive correlation was demonstrated between levels of soluble ICAM-1 in pooled
      FF and the number of retrieved oocytes or the number of follicles with a diameter
      of >15 mm. CONCLUSION(S): Soluble ICAM-1 can be released by granulosa luteal
      cells and can be detected in FF after ovarian hyperstimulation. Levels of soluble
      ICAM-1 in FF correlate directly with some indices of ovarian function.

PMID- 9548173
TI  - Transvaginal drainage of ascites as an alternative to abdominal paracentesis in
      patients with severe ovarian hyperstimulation syndrome, obesity, and generalized
      edema.
AB  - OBJECTIVE: To describe an alternative technique for transvaginal drainage of
      ascites in a case of severe ovarian hyperstimulation syndrome (OHSS), generalized
      edema, and obesity. DESIGN: Case report. SETTING: A university-based hospital IVF
      and Reproductive Medicine Unit. PATIENT(S): A patient hospitalized with severe
      OHSS after IVF-ET in whom drainage of large amounts of ascitic fluid was
      necessary. INTERVENTION(S): Ultrasonographic transvaginal insertion of a wire
      guide through a standard IVF needle into the Douglas pouch. Placement of a "peel
      away" set on the wire, which was replaced with a "pigtail" indwelling catheter.
      MAIN OUTCOME MEASURE(S): Amount of drained ascitic fluid. RESULT(S): Ascitic
      fluid was drained efficiently, leading to improvement of the patient's condition.
      CONCLUSION(S): Transvaginal ultrasonography-guided insertion of a pigtail
      catheter through the Douglas pouch is an efficacious procedure when the abdominal
      approach for decompression of ascites is difficult.

PMID- 9548174
TI  - A new assisted hatching technique using a piezo-micromanipulator.
AB  - OBJECTIVE: To estimate the efficacy of a new assisted hatching technique using a
      piezo-micromanipulator to support embryonic implantation. DESIGN: Sibling spare
      embryos from human cycles of IVF were allocated to either a treated group for
      assisted hatching by a piezo-micromanipulator or a nontreated control group.
      SETTING: The Infertility and IVF unit of the Kyoto University Hospital.
      PATIENT(S): Sixty-eight women undergoing conventional IVF treatment.
      INTERVENTION(S): One hundred ten spare 4- or 8-cell embryos from 68 patients
      undergoing IVF were treated with the new assisted hatching technique, and the
      results were compared with those obtained for 112 sibling embryos without the
      treatment. In the assisted hatching procedure, zona thinning combined with
      drilling was performed by the vibration of a microneedle produced by the piezo
      micromanipulator unit. MAIN OUTCOME MEASURE(S): The rates of partial hatching and
      completely hatched blastocysts. RESULT(S): The rates of hatching and of hatched
      blastocysts per total developing blastocysts were significantly higher in the
      treated group (86.7% and 33.3%, respectively) than in the control group (15.3%
      and 2.8%, respectively). CONCLUSION(S): These results demonstrate that the newly
      devised zona thinning and drilling technique using a piezo-micromanipulator is
      useful for assisted hatching.

PMID- 9548175
TI  - Carrot juice junkies and big bangs.

PMID- 9548176
TI  - Clarification of fertility after tubal surgery for ectopic pregnancy.

PMID- 9548177
TI  - Clarification of fertility after tubal surgery for ectopic pregnancy.

PMID- 9548179
TI  - Fibroblast growth factor-2 and fibroblast growth factor receptor-1 mRNA
      expression and peptide localization in placentae from normal and diabetic
      pregnancies.
AB  - Fibroblast growth factor-2 (FGF-2) is a potent mitogen expressed widely during
      embryogenesis and in tissues of the human fetus. It is recognized as an
      endothelial cell mitogen and is angiogenic in vivo. Expression of FGF-2 mRNA has
      also been shown within the human term placenta, and FGF-2 isolated from placental
      tissue, suggesting a role in placental growth including angiogenesis. The purpose
      of this study was to quantify and localize the sites of expression of FGF-2 and
      its high-affinity receptor, FGFR1, within placentae from normal term human
      pregnancies (n=8, 39-42 weeks), and pregnancies complicated by pregestational,
      type 1 diabetes (n=8, 36-40 weeks). Tissues were collected immediately following
      delivery and were either snap-frozen for RNA isolation, or fixed for either in
      situ hybridization using a 35S-labelled cRNAs encoding human FGF-2 or FGFR1, or
      immunocytochemistry using antibodies against human FGF-2 or FGFR1. Northern blot
      hybridization showed a significantly increased abundance of mRNAs for both FGF-2
      and FGFR1 in placentae from diabetic women compared to those from normal women.
      In normal term placenta FGF-2 mRNA was present at low abundance in fetal villous
      tissue, in the vascular endothelium of blood vessels, and in the
      syncytiotrophoblast. FGF-2 mRNA was considerably more abundant in the
      syncytiotrophoblast and villous tissue of placentae from diabetic patients.
      Messenger RNA for FGFR1 was similarly distributed to that encoding FGF-2.
      Immunocytochemistry revealed abundant FGF-2 and FGFR1 peptides in villous
      vascular endothelial cells, and associated with the cell membranes of stromal
      tissues in placentae from control pregnancies. Little immunoreactive FGF-2 was
      present in the syncytiotrophoblast at term. In pregnancies complicated by
      diabetes intense staining for immunoreactive FGF-2 and for FGFR1 additionally
      existed in syncytiotrophoblast. The results suggest that FGF-2 acting as an
      autocrine agent contributes to placental angiogenesis, but may be released from
      the syncytium into the maternal circulation. Expression is elevated in placentae
      from diabetic pregnancies, and is particularly associated with the
      syncytiotrophoblast. This suggests a placental source for the elevated
      circulating maternal FGF-2 previously described in diabetic pregnancy.

PMID- 9548178
TI  - HLA-G1 protein expression is not essential for fetal survival.
AB  - HLA-G is a nonclassical, class I HLA gene that is primarily expressed by fetal
      cells at the maternal-fetal interface and is thought to play a key role in the
      induction of tolerance in pregnancy. This paper reports the identification of a
      single base pair deletion at position 1597 (1597delC) in exon 3 (encoding the
      alpha2-domain) of HLA-G on 20 of 272 (7.4 per cent) African American chromosomes,
      three of 102 (2.9 per cent) Hispanic chromosomes, and none of 134 Caucasian
      chromosomes. This relatively common frameshift mutation results in amino acid
      substitutions in all of the residues in the second half of exon 3 including the
      conserved cysteine at codon 164. An adult individual was identified who was
      homozygous for this 'null' allele, and a first trimester placenta that was
      homozygous for 1597delC had no detectable HLA-G1 protein. These data indicate
      that expression of HLA-G1 protein is not essential for fetal survival.

PMID- 9548180
TI  - Fetal growth retardation and second trimester maternal serum human chorionic
      gonadotrophin levels.
AB  - Second trimester maternal serum human chorionic gonadotrophin (hCG) levels in
      women who remained normotensive but delivered an unexplained growth retarded
      infant were compared with those from a control group and a group of women who
      developed pre-eclampsia in a retrospective observational study. Our hypothesis
      was that the similar placental pathological changes shared by unexplained
      normotensive IUGR and pre-eclampsia would be reflected by elevated maternal serum
      hCG levels in the second trimester. Normotensive women delivering unexplained
      singleton growth retarded infants were identified (n=43) and their second
      trimester hCG levels, taken as part of antenatal screening for Down's syndrome,
      were obtained. These were compared with a control group of 625 women, and a group
      of 48 women who subsequently developed pre-eclampsia. There was no significant
      difference in the hCG levels expressed as multiples of the median (MOM) between
      the women who delivered growth retarded fetuses (median MOM 0.96) and the control
      group (median MOM 0.97). The levels of hCG in the women who subsequently
      developed pre-eclampsia were significantly higher (median MOM 1.3, P=0.008).
      There were no significant differences in AFP levels in the three groups; however,
      the trend was towards a higher level of AFP in the fetal growth retardation
      group. Maternal serum hCG in the second trimester does not appear to be elevated
      in normotensive women who later produce a growth retarded fetus, although human
      chorionic gonadotrophin levels are significantly higher in women who subsequently
      develop pre-eclampsia.

PMID- 9548181
TI  - Evidence for basic fibroblast growth factor as a crucial angiogenic growth
      factor, released from human trophoblasts during early gestation.
AB  - The objective of this study was to clarify the possible angiogenesis-promoting
      factors from human trophoblasts in early stage gestation. The existence of
      angiogenic growth factors such as basic fibroblast growth factor (bFGF) and
      vascular endothelial growth factor (VEGF) in the condition medium from human
      villous trophoblasts was determined. Biological activity of angiogenic growth
      factors released by trophoblasts was examined using vascular endothelial cell
      lines. The condition medium from trophoblasts enhanced the growth of endothelial
      cells. Although cultured trophoblasts exhibited immunoreactive products for both
      bFGF and VEGF in the cytoplasm, only bFGF was detected in the condition medium by
      ELISA. The growth-enhancing activity of the condition medium was eliminated
      completely by the addition of anti-bFGF antibody but not with anti-VEGF antibody.
      Thus, trophoblastic cells seem to play an important role in extensive
      angiogenesis occurring in early gestation, mainly by releasing bFGF but not VEGF.

PMID- 9548183
TI  - Expression of cytokine receptors in the placenta in term and preterm labour.
AB  - Elevated uterine concentrations of interleukin-1beta (IL-1beta), interleukin-6
      (IL-6) and tumour-necrosis factor-alpha (TNF-alpha) are suspected to cause
      increased prostaglandin release from gestational tissues, but little information
      is available about the expression pattern of cytokine receptors in these tissues.
      In this study, cytokine receptor positive cells in frozen tissue sections of
      placentae (n=70) and fetal membranes (n=50) were identified by immunohistological
      staining with monoclonal antibodies specific for IL-6 receptor, TNF receptors I
      and II, and IL-1 receptor I. Both subunits of the IL-6 receptor (gp130 and gp80)
      as well as TNF receptors I and II were expressed by fetal endothelial cells
      within placental villi, while IL-1-receptor I was detected exclusively in stromal
      cells of the maternal decidua. The IL-1 receptor I and TNF receptors I and II
      were expressed in both uterine quiescence and labour, irrespective of gestational
      age. Immunoreactivity of the gp130 subunit of the IL-6 receptor was found also
      throughout pregnancy, while the appearance of the gp80 subunit correlated with
      the presence of term and preterm labour. In case of preterm labour, expression of
      the gp80 subunit was predominantly detected in the absence of intrauterine
      infection. Therefore, it is concluded that the de novo expression of the gp80
      subunit and consequently the appearance of entire IL-6 receptors in the placenta
      is associated with spontaneously occurring labour at term and also with preterm
      occurring labour in the absence of inrauterine infection.

PMID- 9548182
TI  - Expression of syndecan-1 in human placenta and decidua.
AB  - Syndecan-1 is a cell surface heparan sulphate proteoglycan, which binds to the
      extracellular matrix (ECM), growth factors and antithrombin III. The early
      expression of syndecan-1 during mouse embryonic development suggests a potential
      role in the communication between the embryo and the ECM of decidua. Using
      immunohistochemical methods, the present study showed that the expression of
      syndecan-1 in the trophoblast cells changes along trophoblast differentiation.
      The syncytiotrophoblasts in the chorionic villi exhibited an apical expression of
      syndecan-1. This suggests that the expression is restricted to non-migrating, non
      proliferating trophoblasts. The mode of syndecan-1 expression by human placental
      trophoblasts is independent of gestational age. The expression is not changed in
      miscarriages. In pre-eclampsia, the staining for syndecan-1 on the villous
      syncytiotrophoblast is weaker compared to normal pregnancy, but in placental bed
      the expression is similar. The unique apical localization of syndecan-1 in
      chorionic villi, not detected in any other tissues, suggests a potential role in
      fetomaternal communication probably via growth factor binding and in
      anticoagulation of intervillous circulation.

PMID- 9548184
TI  - Localization and distribution of tissue type and urokinase type plasminogen
      activators and their inhibitors Type 1 and 2 in human and rhesus monkey fetal
      membranes.
AB  - Fetal membranes consist of 10 distinct layers including components of amnion,
      chorion and decidua, the latter being of maternal origin. They form mechanically
      integrated sheets capable of retaining amniotic fluid and play an essential role
      in protecting fetal growth and development in the pregnant uterus. The
      extracellular matrix, substrate for plasminogen activators (PAs), is an important
      supportive framework of the fetal membranes. Fetal membranes from women with
      preterm premature rupture of membranes may differ in their protease activity
      compared with normal membranes. To identify the presence of PAs and their
      inhibitors (PAI) and their possible role in the process of fetal membrane
      rupture, this study investigated the distribution and localization of both
      protein and mRNA for tissue (t) and urokinase (u) PA and their inhibitors type 1
      (PAI-1) and type 2 (PAI-2) in amniochorion of human and rhesus monkey using
      conventional and confocal immunofluorescence microscopy. In situ hybridization
      analysis showed that the distribution and localization of mRNAs for tPA, uPA, PAI
      1 and PAI-2 were similar in the fetal membranes of human and rhesus monkey; no
      obvious species difference was observed. Evidence of tPA mRNA was detected in
      amniotic epithelium, trophoblast cells and nearly all cells of the decidual
      layer. Strong expression of uPA mRNA was noted in the decidual cells which
      increased in intensity as the abscission point was approached. Weak staining in
      chorion laeve trophoblast was also detected. In situ hybridization experiments
      showed PAI-1 mRNA to be concentrated mainly in the decidual cells, some of which
      were interposed into the maternal-facing edge of the chorion laeve. Maximal
      labelling of the decidua occurred towards the zone of abscission. Weak expression
      of PAI-1 mRNA was also noted in some cells of the chorion laeve. The distribution
      of PAI-2 mRNA in amniochorion was also concentrated in the cells of the decidual
      layer, maximum expression of the mRNA was in the level of abscission. No
      detectable amount of mRNAs for tPA, uPA, PAI-1 and PAI-2 was found in the
      fibroblast, reticular and spongy layers. Distribution of the proteins of tPA, uPA
      and PAI-1 in the fetal membranes of these two species was consistent with the
      distribution of their mRNA. Anti-PAI-2 immunofluorescence was found to be
      strongly concentrated in the amniotic epithelium, but PAI-2 mRNA was negative in
      this layer, suggesting that the epithelium-associated PAI-2 is not of epithelial
      origin. These findings suggest that a local fibrinolysis in fetal membranes
      generated by precisely balanced expression of PAs and their inhibitors via
      paracrine or autocrine mechanisms may play an essential role in fetal membrane
      development, maturation and in membrane rupture. Following an analysis of the
      distribution and synthesis of activators and inhibitors it was found that they
      may play a role in abscission during the third stage of labour.

PMID- 9548185
TI  - Eosinophil cationic protein and eosinophil protein X: human amniotic fluid
      concentrations and gestational tissue content at term.
AB  - The aim of this study was to determine the presence and concentration of
      immunoreactive eosinophil cationic protein (ECP) and eosinophil protein X (EPX)
      in human amniotic fluid at term and assess labour-associated changes in their
      mean concentrations. In addition, ECP and EPX content in term amnion,
      choriodecidua and placenta obtained before and after labour and delivery was
      established. Immunoreactive ECP and EPX were identified in all samples of
      amniotic fluid (n=47) and gestational tissue (n=60) assayed. EPX was
      quantitatively more abundant than ECP in both amniotic fluid and gestational
      tissues. In amniotic fluid, ECP and EPX concentrations increased 8-fold (P<0.02)
      and 1.5-fold (P<0.02), respectively, with labour onset. In gestational tissues, a
      labour-associated change in tissue content was only identified for ECP in
      choriodecidua, which increased 1.9-fold with labour and delivery (P<0.01). The
      labour-associated increase in amniotic fluid concentrations of ECP and EPX
      demonstrated in this study is consistent with the well-characterized role of
      these proteins in inflammatory reactions. It remains to be established whether
      the observed increase in ECP and EPX amniotic fluid concentrations is an
      epiphenomenon of labour onset or is involved causally in this process.

PMID- 9548186
TI  - Ovine placentome morphology: effect of high altitude, long-term hypoxia.
AB  - The effect of high altitude, long-term hypoxaemia on placentome morphology in the
      sheep was examined using singleton and twin pregnant ewes. Normoxic twins had
      lower fetal and placental weights (3.7+/-0.2 kg and 215+/-26 g, respectively)
      than normoxic singleton fetuses (4.3+/-0.2 kg and 336+/-17 g, respectively).
      Fetal and placental weights were similar in normoxic singleton and high altitude
      (3820 m) hypoxic singleton fetuses (4.3+/-0.2 and 4.4+/-0.4 kg, 336+/-17 and
      342+/-62 g, respectively). The distribution of placentome types was classified
      into four major categories (A-D) and for normoxic singletons was as follows:
      A=76+/-4, B=22+/-3, C=1+/-2, and D=1+/-1. Normoxic twins tended to have more type
      B (type A=63+/-10, B=33+/-8, C=2+/-1, and D=2+/-1). High altitude hypoxic
      singletons had significantly fewer type A (33+/-4) and more type B (50+/-3), C
      (10+/-7), D (7+/-1) placentomes than normoxic singletons. In addition, in the sea
      level control group, five animals were found to be spontaneously hypoxic with a
      placentome distribution similar to that of the high altitude hypoxic fetuses. In
      conclusion, both high altitude, long-term hypoxia and low altitude spontaneous
      hypoxia lead to a significant change in placentome distribution with less type A
      and increases in types B, C and D. Physiologically, the change in the several
      placentome types with high altitude hypoxia suggests an acclimatization response
      to optimize transplacental exchange efficiency.

PMID- 9548187
TI  - Haemodynamic model of twin-twin transfusion syndrome in monochorionic twin
      pregnancies.
AB  - Twin-twin transfusion syndrome in monochorionic twin pregnancies is not
      understood completely and is controversial which hampers development of
      acceptable diagnostic and rational treatment strategies. A haemodynamic model was
      developed that relates fetal growth with (1) fetoplacental blood flow and
      fetomaternal effects, and (2) net twin-twin transfusion from donor to recipient
      twin. Fluid balance mechanisms were neglected. Placental vascular anastomoses
      (arteriovenous, venoarterial, arterioarterial, venovenous) were modelled as
      straight blood vessels connecting the placental cord insertions that grow during
      pregnancy. Poiseuille's law predicts significantly decreasing anastomosing
      resistances, and when placental sharing is unequal it is assumed that smaller
      placental fractions cause smaller blood volumes and pressures. Two coupled first
      order differential equations describing each twin's blood volume were determined
      and analysis showed that placental and anastomotic development cause anastomotic
      blood flow to increase faster than fetal growth. Hence, it is proposed as the
      syndrome's underlying pathophysiology that fetal discordance increases
      progressively, beyond fetal compensatory capacity. Fewer anastomoses cause larger
      discordance, but its onset can vary widely during pregnancy. Arteriovenous plus
      compensating anastomoses produce dynamic steady-state growth patterns with large,
      opposite, measurable anastomotic blood flows. Clinical study of fetal growth
      patterns may identify the syndrome's underlying placental anatomy. Predicted
      trends depend only weakly on implemented fetal physiology and are most likely
      realistic. This knowledge could improve future management of the syndrome.

PMID- 9548188
TI  - Overlay blot identification of GTP-binding proteins in mitochondria from human
      placenta.
AB  - In this study, an overlay blot method was used to identify GTP-binding proteins
      in fractions of human placenta. Human placenta were fractionated by
      centrifugation into preparations containing (1) mitochondria, (2) nucleoli and
      (3) microsomes, plasma membrane and cytosol. GTP-binding proteins were detected
      by overlay blot using alpha32P-GTP. Proteins of 23 and 25 kDa were identified in
      all fractions and GTP binding was higher in the presence of 1.0, 2.5, 5.0 and
      10.0 mM MgCl2 as compared to equivalent concentrations of CaCl2. In mitochondrial
      preparations binding of alpha32P-GTP to 23 and 25 kDa was displaced significantly
      by GDP and GTP but not ADP or ATP. Fractions containing microsomes, plasma
      membrane and cytosol displayed two labelled bands of 14 and 18 kDa that were not
      present in other fractions. These data indicate that the placenta contains
      specific GTP-binding proteins of molecular weights that are consistent with the
      small monomeric GTP binding protein family (18-36 kDa). Two of these are located
      in the mitochondria and may regulate the function of these organelles in the
      placenta.

PMID- 9548189
TI  - Specific expression of PP5/TFPI2 mRNA by syncytiotrophoblasts in human placenta
      as revealed by in situ hybridization.
AB  - Placental protein 5 (PP5) is a placenta-derived glycoprotein with serine
      proteinase-inhibiting activity. To date its physiological functions have not been
      well elucidated. Recently, cDNA sequence analysis revealed that PP5 belongs to
      the Kunitz-type proteinase inhibitor family and it is identical to tissue factor
      pathway inhibitor-2 (TFPI-2), homologous to TFPI. Northern blot analysis
      demonstrated that placental tissue is extremely rich in the transcripts. This
      study localized PP5/TFPI-2 mRNA in placental tissues at three different
      gestational periods using in situ hybridization. PP5/TFPI-2 mRNA was specifically
      detected in syncytiotrophoblast at any gestational period examined, suggesting
      that syncytiotrophoblast is the principal production site of PP5/TFPI-2 in
      developing placental tissues. This mRNA expression pattern of PP5/TFPI-2 is quite
      different from that of TFPI, which is mainly found in vascular endothelial cells.
      The results indicated possible roles of PP5/TFPI-2 in the trophoblast
      differentiation and in the maintenance of intervillous blood flow. Also, Northern
      analysis demonstrated no or little expression of PP5/TFPI-2 in four
      choriocarcinoma cell lines, in contrast to its abundant expression in
      syncytiotrophoblast.

PMID- 9548190
TI  - Determinants of species- and placenta-specific expression of p100 GAP.
AB  - This study was based on the hypothesis that both primary sequence and methylation
      status of the GTPase activating protein (GAP) gene limits expression of p100 GAP
      to primate placenta. Due to alternate splicing, a 65-bp insert appears between
      the first and second coding exons of p100 GAP mRNA, and translation of p100 GAP
      initiates within this insert. Examination of the sequence surrounding the 65-bp
      insert revealed that the monkey GAP gene contained both the 3' splice donor site
      and the internal start codon, whereas the mouse GAP gene contained neither. To
      address p100 GAP tissue specificity, the methylation status of the GAP gene was
      examined. Site-specific demethylation was found to correlate with synthesis of
      p100 GAP, suggesting that methylation regulates the expression of different GAP
      isoforms. The results of this study provide a mechanistic basis for the
      observation that p100 GAP is synthesized only in primate placenta and suggest
      that its expression is regulated, in part, by gene methylation.

PMID- 9548191
TI  - Progress with nuclear medicine audit in the UK.

PMID- 9548192
TI  - FDG uptake, tumour characteristics and response to therapy: a review.
AB  - The use of FDG-PET imaging in tumour detection is now well established. Many
      studies have suggested that changes in the uptake of FDG predict tumour response
      to therapy and that further clinical information regarding tumour grade and
      proliferative status may also be derived from FDG-uptake scans. More studies are
      required to verify the role of FDG-PET in patient management. Upregulation of
      hexokinase and glucose transporters, especially Glut-1, and downregulation of
      glucose-6-phosphatase are frequently associated with transformation. The extent
      of these changes has been related to both differentiation and proliferation
      largely corresponding with FDG-uptake studies.

PMID- 9548193
TI  - A structured approach to the interpretation and reporting of
      ventilation/perfusion scans.
AB  - The aim of this study was to develop a structured approach to the reporting and
      in particular the clinical interpretation of ventilation/perfusion (V/Q) scan
      results. An initial audit indicated that there were significant variations in the
      clinical management of patients particularly after a non-diagnostic V/Q scan
      report. There were also differences in the approaches used to interpret the scan
      itself. In an attempt to improve this, a set of interpretation guidelines was
      produced based on the revised PIOPED data. To combat the problems with clinical
      interpretation, a standard method for assessing the pre-test clinical probability
      of pulmonary embolism was established. This clinical risk was then combined with
      the V/Q scan result to give an overall probability for the presence of pulmonary
      embolism. The more precise risk stratification which resulted allowed explicit
      clinical advice on patient management to be incorporated into the final report. A
      second audit was performed with the revised methodology in place. The level of
      inter-observer variability for scan reporting decreased from 30% to 12%. The
      prior assessment of clinical risk and the standardized method of combining this
      with the scan result led to an improvement in patient management. This was
      particularly true for the non-diagnostic group, in whom additional investigations
      were more appropriately used. A structured approach which allows the pre-test
      probability of pulmonary embolism to be combined in an explicit fashion with the
      V/Q scan result can provide a more precise risk stratification allowing
      appropriate recommendations to be made. Such an approach can result in improved
      patient management.

PMID- 9548194
TI  - A preliminary evaluation of diagnostic odds in lung scan reporting.
AB  - Reporting of lung scans for pulmonary embolism (PE) using a descriptive
      probability notation is tried and tested. Subjectivity in interpretation of this
      jargon can be a problem for internists. Parallel descriptive and numerical
      probability reporting has been recommended, but the numerical probability scale
      is less precise than likelihood ratios expressed as odds. We therefore assessed
      internists' intuitive understanding of lung scan reports in the odds format
      compared to the descriptive probability notation. A questionnaire was sent to
      Scotland's 217 internists to assess their intuitive understanding of odds
      reporting and to compare their management strategies when confronted by lung scan
      reports in both an odds and a descriptive probability notation. There was a broad
      understanding of numerical odds. Internists used 'normal' and '100:1 against PE'
      identically; similarly, 'low probability' and '10:1 against PE'. There was a
      statistically significant preference for the diagnosis of PE when internists were
      given the '1:1 evens' report compared with the 'indeterminate' report. There does
      appear to be a greater awareness of the risk of PE when non-diagnostic lung scans
      are reported in numerical odds as compared with the descriptive probability
      format.

PMID- 9548195
TI  - Comparison of dual-isotope acquisition of 201Tl and 99Tcm-tetrofosmin for the
      detection of ischaemic heart disease and determination of the optimal imaging
      time of 99Tcm-tetrofosmin.
AB  - Comparative studies of thallium-201 (201Tl) and 99Tcm-tetrofosmin for the
      detection of ischaemic heart disease (IHD) have previously been reported. These
      201Tl and 99Tcm-tetrofosmin studies were usually performed separately with
      different exercise loads at an interval of several days. Here, we used a dual
      isotope technique with exercise myocardial SPET (single photon emission
      tomography) in 17 patients with IHD and 10 patients with normal coronary
      arteries. The triple-energy window (TEW) method was applied for cross-talk
      correction. SPET imaging was performed at 10 and 70 min (S1 and S2) after the
      injection of 99Tcm-tetrofosmin (222 MBq) and 201Tl (74 MBq) at peak exercise to
      determine the optimal imaging time of 99Tcm-tetrofosmin. The S2 value was
      obtained 35 min after the subject drank a glass of milk to accelerate
      hepatobiliary clearance. Twenty-five minutes after S2, 37 MBq of 201Tl were
      reinjected at rest and SPET imaging (S3) was performed. Immediately after S3, 666
      MBq of 99Tcm-tetrofosmin were reinjected and SPET imaging (S4) was performed 50
      min later. Representative short and vertical long axis tomograms were divided
      into 17 segments. Each segment was assessed using a 4-point scoring system. The
      defect score was defined as the sum of each segmental score. The defect scores
      for imaging at exercise were 14.3 +/- 11.4 for 201Tl at S1, 11.4 +/- 8 for 99Tcm
      tetrofosmin at S1 and 9.7 +/-9.8 for 99Tcm-tetrofosmin at S2 (P < 0.01),
      respectively. The washout rate of 99Tcm-tetrofosmin for the first hour was 15.5
      +/- 7.3% and 11.8 +/- 7.7% (P < 0.01), respectively, for the normal and ischaemic
      segments. The image quality of 201Tl at S1 was almost equivalent to that of 99Tcm
      tetrofosmin at S1/S2. The overall sensitivity and specificity for the detection
      of ischaemia was 94% and 82% for 201Tl at S1, 89% and 86% for 99Tcm-tetrofosmin
      at S1, and 88% and 95% for 99Tcm-tetrofosmin at S2, respectively. The overall
      accuracy was 86%, 88% and 92%, respectively. The myocardial viability score was
      7.4 +/- 7.1 for 201Tl at S3 and 5.8 +/- 7.0 for 99Tcm-tetrofosmin at S4 (P <
      0.01). The results indicate that the diagnostic accuracy of 99Tcm-tetrofosmin for
      myocardial ischaemia is almost equivalent to that of 201Tl as assessed by dual
      SPET imaging, and that the optimal imaging time for 99Tcm-tetrofosmin is within
      10-35 min (S1) after exercise.

PMID- 9548196
TI  - The role of 99Tcm-tetrofosmin myocardial perfusion scintigraphy in the assessment
      of patients with previous myocardial infarction: a comparative study with 201Tl.
AB  - The aim of this study was to determine the utility of 99Tcm-tetrofosmin cardiac
      imaging in patients with previous myocardial infarction and with significant
      coronary artery disease (CAD) compared with that of 201Tl cardiac imaging.
      Sixteen patients (14 males, 2 females) were studied by same-day exercise-rest
      99Tcm-tetrofosmin imaging and exercise, rest and reinjection 201Tl cardiac
      imaging. For each study, semi-quantitative visual analysis was performed in 20
      segments using a 4-point scale. The regional distribution and defect
      reversibility with the two tracers were compared with the results of coronary
      angiography. A total of 320 segments were analysed. There was a statistically
      significant concordance between the numbers of fixed and reversible segments in
      both studies in myocardial segments supplied by totally occluded coronary
      arteries (Group 1), as well as in segments supplied by significantly stenosed
      coronary vessels (Group 2). The exercise and rest uptake of both 99Tcm
      tetrofosmin and 201Tl in myocardial segments supplied by totally occluded
      coronary arteries with poor collateral flow was significantly lower compared with
      segments supplied by totally occluded coronary arteries with efficient collateral
      flow (P < or = 0.05). When the uptake of both tracers was analysed according to
      each major vascular territory, the mean exercise and rest uptake grades of 99Tcm
      tetrofosmin and 201Tl were similar. There was also no significant difference in
      defect reversibility between the two tracers. Discordant results were observed in
      the territory of the right coronary artery in Group 1 (mean exercise grade of
      99Tcm-tetrofosmin = 2.26 +/- 0.7 and of 201Tl = 1.92 +/- 0.8; P < or = 0.001) and
      in Group 2 (mean grade of 99Tcm-tetrofosmin = 0.79 +/- 0.65 and of 201Tl = 0.95
      +/- 0.65; P < or = 0.05). The results of the present study indicate that the
      overall diagnostic utility of 99Tcm-tetrofosmin in the identification of
      individual stenosed vessels is comparable with 201Tl in both patients with
      totally occluded coronary arteries and those with significantly stenosed vessels.
      The regional distribution of both tracers was lower in myocardial segments
      supplied by totally occluded coronary arteries with poor collateral flow.

PMID- 9548197
TI  - Decreased myocardial accumulation of 123I-meta-iodobenzyl guanidine in
      Parkinson's disease.
AB  - The aim of this study was to evaluate 123I-meta-iodobenzyl guanidine (123I-MIBG)
      myocardial scintigraphy in patients with Parkinson's disease as a way of
      detecting cardiac sympathetic dysfunction, and comparing the stage of disease and
      intensity of drug treatment with accumulation of 123I-MIBG. 123I-MIBG myocardial
      scintigraphy was performed in 48 patients with Parkinson's disease and 25 control
      subjects. In the planar imaging studies, the data acquisition matrix was 256 x
      256 and the preset time was 5 min. The heart-to-mediastinum (H/M) average count
      ratio was calculated for both early (15 min) and delayed (3-4 h) images after
      123I-MIBG injection (111 MBq). The mean H/M ratio in patients with Parkinson's
      disease was significantly lower than that in the controls (P < 0.0001).
      Regardless of disease severity, intensity of anti-Parkinson treatment and the
      presence or absence of orthostatic hypotension, the mean H/M ratios were always
      low in the Parkinsonian patients. Parkinson's disease may result in a severe
      abnormality of cardiac sympathetic function which has not been detected by
      previous cardiovascular autonomic studies.

PMID- 9548198
TI  - A dual-tracer method for studying intragastric distribution and gastric emptying
      of solids and liquids in functional dyspepsia.
AB  - Twenty-five patients with functional dyspepsia and 11 healthy controls matched
      for age and sex were examined. The patients were divided into two groups:
      patients with dysmotility-like symptoms and those with ulcer-like symptoms. In a
      dual-tracer gastric emptying study, dysmotility-like and ulcer-like symptoms
      could not be distinguished from each other on the basis of gastric emptying
      times. The intragastric distribution and the solid lag time in dysmotility-like
      dyspepsia differed significantly from those of the controls.

PMID- 9548199
TI  - Age- and sex-related 99Tcm-DMSA renal uptake at 24 h in children with a normal
      scintigram.
AB  - We performed a retrospective study to determine the age- and sex-related normal
      values of absolute 99Tcm-DMSA uptake at 24 h in children with normal kidneys. Of
      the 576 scintigrams performed between 1993 and 1996, 136 (272 kidneys) were
      classified as 'normal' by two independent observers on the basis of the presence
      of a smooth cortical outline, the absence of cortical loss, relative uptake in
      the range 45-55% and normal echographic parenchymal findings. The 136 scintigrams
      were divided into eight groups based on the children's age: Group I, < 1 month (2
      boys); Group II, 1-3 months (6 boys, 8 girls); Group III, 4-7 months (7 boys, 6
      girls); Group IV, 8-12 months (8 boys, 8 girls); Group V, 13-24 months (14 boys,
      4 girls); Group VI, 25-36 months (6 boys, 13 girls); Group VII, 37-120 months (13
      boys, 19 girls); Group VIII, 121-180 months (8 boys, 10 girls). In contrast to
      the results of Morris et al. using absolute 99Tcm-DMSA uptake at 4-6 h, we found
      that combined left and right kidney uptake increased until age 8 months (Group I,
      22.0 +/- 6.7%; Group II, 45.9 +/- 5.0%; Group III, 50.8 +/- 5.0%; Group IV, 56.9
      +/- 8.5%; P = 0.019), after which it reached a plateau (Group V, 55.4 +/- 7.3%;
      Group VI, 60.1 +/- 7.8%; Group VII, 62.0 +/- 5.0%; Group VIII, 62.4 +/- 6.3%).
      Uptake at 24 h tended to be lower in the girls than in the boys, but this
      difference was not significant.

PMID- 9548200
TI  - Evaluation of renal function following treatment with extracorporeal shock wave
      lithotripsy (ESWL): the use of whole-kidney, parenchymal and pelvic transit
      times.
AB  - The aim of this prospective study was to assess the efficacy of using whole
      kidney, mean parenchymal and pelvic transit times to evaluate renal function
      following treatment with extracorporeal shock wave lithotripsy (ESWL). Fifteen
      patients were evaluated 24-48 h before and after ESWL therapy using 99Tcm-DTPA
      renal scintigraphy. Using deconvolution analysis, whole-kidney, mean parenchymal
      and pelvic transit times were calculated and the pre-ESWL values were compared
      with the post-ESWL values. In both kidneys, there were no significant changes in
      the glomerular filtration rate or relative renal uptake when compared with the
      pre-ESWL values. The mean whole-kidney transit time of the tracer did not change
      significantly during the post-ESWL period. In the treated kidney, the mean post
      ESWL parenchymal transit time was significantly increased (P < 0.05), while the
      mean pelvic transit time was significantly decreased (P < 0.05). In the untreated
      kidney, there were no significant changes in any of these parameters. We conclude
      that the dual use of parenchymal and pelvic transit times is more sensitive than
      the mean whole-kidney transit time and other measures, such as glomerular
      filtration rate and relative renal uptake, for the assessment of outcome of
      therapy and other related post-ESWL changes.

PMID- 9548201
TI  - Hybrid phantoms for testing the measurement of regional dynamics in dynamic renal
      scintigraphy.
AB  - A hybrid phantom is a synthetic dynamic scintigraphic study reconstructed from
      dynamic components of real clinical data. The aim of a hybrid simulation is to
      provide realistic reference studies with systematically varying quantitative
      diagnostic parameters for testing the quality of measurement of regional
      dynamics. The components of the phantom are extracted from a representative
      patient study using factor analysis. Prior to the construction of the phantom,
      selected components are modified in a known way or substituted with heterologous
      data. The phantom study is constituted from the altered components using a
      procedure inverse to factor analysis, and completed by the addition of residual
      noise. The hybrid phantom is a compromise between simulated and software
      phantoms. Unlike simulated phantoms, it preserves a significant part of data
      variability and the natural complex structure of scintigraphic images. Unlike
      software phantoms, it provides values for selected diagnostic parameters or
      magnitudes of their relative changes. A set of hybrid phantoms from a dynamic
      renal study and the results of a pilot clinical evaluation are presented.

PMID- 9548202
TI  - 188Re(V)-DMSA revisited: preparation and biodistribution of a potential
      radiotherapeutic agent with low kidney uptake.
AB  - Methods of preparation and biodistribution in mice of tin-free 99Tcm(V)-DMSA and
      188Re(V)-DMSA, a potential matching pair of radiopharmaceuticals for diagnosis
      and therapy of certain cancers, are described. Preparation of tin-free 188Re(V)
      DMSA (I) is based on reduction with either SO2-releasing compounds like Na2S2O4
      (30 mg Na2S2O4, 10 mg DMSA, 1 mg L-ascorbic acid, 37 degrees C, 60 min
      incubation), Na2S2O5 (as before, 70 degrees C, 15 min incubation), or HBr (0.2 ml
      48% HBr, 0.2 ml 7 M HCl, 10 mg DMSA, 1 mg L-ascorbic acid, 70 degrees C, 60 min
      incubation). I exhibits significantly lower kidney uptake than tin-containing
      188Re(V)-DMSA (II) (2-3% and 49% injected dose per gram organ, 1 h post
      injection, respectively). HPLC profiles of I and II are similar. DMSA excess in
      tin-free 188Re(V)-DMSA is not responsible for the low kidney uptake of I. High
      kidney uptake of II is explained by formation of a mixed 188Re(V)-Sn-DMSA complex
      in vivo. Age-linked bone uptake in mice dependent on the maturation of the bone
      is demonstrated for both I and II.

PMID- 9548203
TI  - Salivary gland scintigraphy after radioiodine therapy.

PMID- 9548204
TI  - In vivo function tests of hepatic drug-oxidizing capacity in patients with liver
      disease.
AB  - Aminopyrine, antipyrine and trimethadione have been widely used for some time as
      probe drugs to assess non-selective P450 liver function. They have proved useful
      in evaluating pre- and post-operative liver function when performing surgery,
      transplantations, etc., in addition to a general evaluation of liver function and
      drug interactions. Progress has recently been made both in these non-selective
      P450 function tests and in the analysis of drug-metabolizing enzymes at a
      molecular level, which has resulted in more selective P450 function tests. The
      caffeine (CYP1 A2), chlorzoxazone (CYP2E1), lidocaine (CYP3 A) and midazolam
      (CYP3 A) function tests and the erythromycin breath test (CYP3 A) are currently
      being used as specific probes. The future use of these tests needs to be
      discussed in terms of potential clinical implications.

PMID- 9548205
TI  - Therapeutic advances: donepezil for the treatment of Alzheimer's disease.
AB  - Until recently, few drugs have been available for the treatment of Alzheimer's
      disease. The first such drug to be launched in the U.K. was the
      acetylcholinesterase inhibitor, donepezil. The limited published data on
      donepezil shows only modest cognitive benefit in patients with Alzheimer's
      disease. The cost of diagnosis and drug treatment, the distressing nature of the
      disease and the limited evidence available, pose difficult decisions for the
      introduction of new drugs and the management of this condition.

PMID- 9548206
TI  - Stability of refrigerated and frozen solutions of tropisetron in either
      polyvinylchloride or polyolefin infusion bags.
AB  - OBJECTIVE: To investigate the stability of 50 microg/ml tropisetron in 0.9%
      sodium chloride or 5% dextrose injections on storage in either 100 ml
      polyvinylchloride (Tuliflex) or polyolefin (Clear-flex) infusion bags, at +4
      degrees C and -20 degrees C. METHOD: A stability-indicating high-performance
      liquid chromatography (HPLC) assay was used to measure residual drug at day 0
      (D0), D8, D15, D30, D60 and D90 for each bag. Samples were tested for pH at D0,
      D60 and D90. Frozen samples were thawed in a microwave oven according to a
      validated procedure before analysis. RESULTS: In 0.9% sodium chloride and 5%
      dextrose, no degradation products were observed in any of the chromatograms. No
      admixtures, at any time, contained less than 98.2% of the initial concentration.
      Only minor changes (-0.12 unit) in pH occurred over the storage period. No colour
      or other visual changes were seen in any sample. CONCLUSION: Tropisetron (50
      microg/ml) in either 0.9% sodium chloride or 5% dextrose is chemically stable in
      polyvinylchloride or polyolefin bags for at least 3 months when stored in a
      refrigerator or in a frozen state.

PMID- 9548207
TI  - Appropriateness of self-medication: method development and testing in urban
      Indonesia.
AB  - BACKGROUND: Most illness episodes are treated by self-medication, however, little
      is known about the appropriateness of this self-medication. Moreover, tools to
      evaluate the appropriateness of self-medication still need to be developed. In
      order to monitor the use of drugs by the general public, we developed methodology
      (for evaluation of the appropriateness of self-medication) that would be
      reproducible and would therefore allow comparison over time and between regions.
      METHOD: For each complaint, criteria for appropriate treatment were set, based on
      evaluation of both the efficacy and the risks of the medications used. To keep
      cost at a minimum and to ensure reproducibility, no use was made of expert
      panels. Instead, only internationally recognized printed sources were used.
      RESULTS: This study used data on self-medication collected in urban Indonesia in
      1993. After excluding illness episodes first treated only with traditional drugs,
      non-drug treatments or treated by a health worker, we found that self-medication
      used as a first action was appropriate in 16% of the cases. Fifty-six per cent
      combined appropriate and unnecessary components and 8% included unnecessary
      components only. Sixteen per cent of treatments were considered potentially
      harmful. Only 4.5% of the illness episodes were not treated. Analysis of these
      potentially harmful treatments showed that over use of antihistamine in children
      under 5 years of age, use of prescription drugs and multiple intake of
      paracetamol or antihistamines in different medicines were the main problems. The
      results of this analysis enabled us to set priorities and formulate
      recommendations to rationalize the use of drugs in self-medication. CONCLUSION:
      The proposed methodology should allow international comparisons and the
      evaluation of the impact of future interventions.

PMID- 9548208
TI  - A long-term comparison between enalapril and captopril on insulin sensitivity in
      normotensive non-insulin dependent diabetic volunteers.
AB  - BACKGROUND: There are conflicting reports about the effects of angiotensin
      converting enzyme inhibitors on insulin sensitivity and glycaemic control. In
      addition, the chronic effects of ACEI on insulin sensitivity in normotensive but
      insulin resistant individuals have been controversial. AIM: To determine the long
      term effects of low-dose captopril or enalapril on insulin sensitivity and lipid
      parameters in normotensive non-insulin dependent diabetic volunteers. METHODS:
      Twenty-eight normotensive non-insulin dependent diabetes mellitus subjects on
      diet alone or diet plus oral hypoglycaemic agents were randomized in a single
      blind cross-over study to receive either captopril (12.5 mg daily) or enalapril
      (5 mg daily). Initially, captopril was compared with enalapril for 28 days with a
      28-day washout period between drug regimens. For the long-term study, the
      subjects then remained on the second ACEI for a further 11 months. Insulin
      sensitivity was measured using the isoglycaemic hyperinsulinaemic clamp (insulin
      infusion rate 20 mIU/kg/min) at the start and completion of each part of the
      cross-over study and then at 3, 6 and 12 months of drug therapy. Fasting glucose,
      insulin, HbA1, lipids and lipoproteins were measured at the start of each clamp.
      RESULTS: No first or second order carry-over effects were demonstrated between
      the ACEIs. No differences were detected between enalapril and captopril on
      insulin sensitivity at any of the time points. Statistically significant
      hypotension was avoided, and at doses used the ACEIs did not modify any
      parameters of glycaemic control over the 12-month study period. There were no
      significant alterations in plasma cholesterol, triglycerides, HDL cholesterol or
      Apo A1 levels during the study. CONCLUSIONS: Long-term low-dose ACEIs
      (captopril/enalapril) do not modify insulin sensitivity, glycaemic control or
      lipids in normotensive non-insulin dependent diabetic subjects.

PMID- 9548209
TI  - Improvements are needed in the existing packaging of medicated oils containing
      methyl salicylate.
AB  - In view of the toxic potential of medicated oils containing methyl salicylate, we
      have studied the existing packaging of 10 commonly used preparations from Hong
      Kong and Singapore and identified areas for improvement with respect to the
      prevention of poisonings. They were all packed in translucent bottles without
      child-resistant closures. The methyl salicylate content ranged from 15 to 67%.
      Many preparations also contained other potentially toxic ingredients in
      significant amounts, such as turpentine oil and camphor. The contents of the
      larger bottles could generally be emptied more easily because of the greater size
      of their openings. The product with the highest methyl salicylate content also
      had the biggest opening of all. The threat from ingestion of medicated oils
      containing methyl salicylate can probably be 'reduced' by: (i) using child
      restraint closures; (ii) restricting the size of both the openings and the
      bottles; and (iii) reducing the methyl salicylate content.

PMID- 9548210
TI  - Study protocol: stability of morphine injected without preservative, delivered
      with a disposable infusion device.
AB  - BACKGROUND AND OBJECTIVE: Morphine hydrochloride, a major analgesic drug, is
      being increasingly administered using portable disposable infusion devices. The
      objective of this study was to investigate the stability of morphine in such a
      system at two concentrations (2.50 and 5.00 mg/ ml) over a 30-day period. METHOD:
      High-performance liquid chromatography of stored morphine solutions. RESULTS: The
      best stability was observed with disposable infusion devices filled with a
      morphine solution containing sodium metabisulphite as a preservative. No
      breakdown products were detected after 1 month of storage at room temperature, in
      light or darkness. On the other hand, 2.50 and 5.00 mg/ml morphine solutions
      without sodium metabisulphite, stored in the infusion device led to the formation
      of 0.205% and 0.235% of pseudomorphine, respectively, after 6 days of storage in
      the light, and 1.50% and 0.94% after 30 days storage. CONCLUSION: Morphine
      hydrochloride solutions stored in disposable infusion devices degraded very
      slowly, particularly when preserved with sodium metabisulphite. The solutions are
      stable over 5 days, the maximum period of storage normally required when using
      disposable infusers.

PMID- 9548211
TI  - A retrospective drug utilization evaluation of antihyperlipidaemic agents in a
      medical centre in Taiwan.
AB  - OBJECTIVE: The purpose of this study was to retrospectively evaluate the
      prescribing of antihyperlipidaemic agents in an 800-bed medical centre in
      southern Taiwan. METHODS: A retrospective study based on reviewing medical
      records was conducted using a computerized database. We randomly selected 344
      patients (age range 5-85 years) who received an antihyperlipidaemic agent between
      1 April 1994 and 30 September 1994 and reviewed their medical records. All the
      related data from the date when the antihyperlipidaemic agent was first
      prescribed to 31 December 1994 was assessed. Usage guidelines for
      antihyperlipidaemic agents were defined by referring to the literature and
      specialist opinion. RESULTS: Two hundred and twenty-two patients (64.5%) were
      treated with antihyperlipidaemic agents in accordance with the usage guidelines.
      In addition, most of the treatments complied with the regulations laid down by
      related health insurance programmes. The other 122 cases (35.5%) failed to meet
      any of the indications of the usage guidelines. Only 102 patients (29.7%) had
      their baseline lipid profiles examined and 117 patients (34%) had their baseline
      liver function tested. Over all, very few cases had lipid profiles and liver
      function tests every 3 months while taking antihyperlipidaemic agents. Patients
      who had been prescribed antihyperlipidaemic agents for more than 1 year were
      evaluated to assess the effectiveness of their pharmacological therapy. The
      prescribed doses were found to be lower than recommended in the general
      literature except for patients who received lovastatin and pravastatin.
      CONCLUSIONS: There are many treatment guidelines for hypercholesterolaemia in
      north America and Europe. This study revealed that a large proportion of
      antihyperlipidaemic agents used in our patient population did not comply with
      these general recommendations. Although the reasons for not complying with usage
      guidelines need to be further investigated, our study findings may well serve as
      the basis for further quality management and pharmacoeconomic analysis.

PMID- 9548212
TI  - Topical sodium sulfacetamide/sulfur lotion.

PMID- 9548213
TI  - Vesicular osmometers, vasopression secretion and aquaporin-4: a new mechanism for
      osmoreception?
AB  - This review cites new evidence suggesting a link between the recently discovered
      membrane bound water-selective channel, aquaporin-4 (AQP4), and the mechanism of
      central osmoreception. AQP4 is found in a number of brain regions associated with
      the osmoregulation of vasopressin secretion and thirst, including the supraoptic
      nucleus (SON) and subfornical organ (SFO). AQP4 expression is restricted to
      ependymal cell membranes in the SFO and astrocyte membranes in the SON,
      especially perivascular end foot processes, suggesting that glial cells may
      correspond to Verney's hypothalamic 'vesicular osmometers'. Information on
      osmotic status may thus be conveyed to the neuronal elements of the 'osmoreceptor
      complex' by a neurone-glial interaction.

PMID- 9548214
TI  - Ligand-inducible retinoid X receptor-mediated protein: DNA interactions in the
      retinoic acid receptor beta2 gene promoter in vivo.
AB  - Retinoid X receptors (RXRs) are recently characterized transcription factors that
      are members of the nuclear hormone receptor superfamily. However, it is not known
      whether the endogenous RXR complex requires its ligand for access to its hormone
      response element (HRE) of a target gene in vivo. Hence, dimethyl sulfate-based
      genomic footprinting was carried out to examine occupancy of HREs in the retinoic
      acid (RA) receptor beta2 (RARbeta2) gene promoter in the murine melanoma cell
      line S91 cultured in the absence or presence of T3, all-trans-RA (atRA), or
      CD2624, an RXR-selective retinoid. No footprint was observed at the RA-response
      element (betaRARE) in the absence of ligands. However, a footprint was detected
      at the betaRARE and other cis-acting elements after a 6 h incubation with CD2624
      and atRA. Interestingly, only the betaRARE was footprinted after 60 min
      incubation with CD2624. These results suggest that the endogenous RXR complex can
      interact with an HRE of a target gene in the presence of ligand, and subsequently
      may initiate additional interactions between DNA and other transcription factors.

PMID- 9548215
TI  - Ultrastructural and secretory heterogeneity of fa/fa (Zucker) rat islets.
AB  - Many previous studies of obese rodents documented biochemical changes in
      pancreatic islets that contribute to hyperinsulinemia in vivo. Those studies used
      heterogeneous populations of islets, although the size of islets from obese rats
      ranges from < 100 to > 500 microm. Here, functional and morphological changes in
      size-sorted (< 125 and > 250 microm diameter) islets from obese Zucker (fa/fa)
      rats were correlated. Ultrastructural examination revealed that > 250 microm
      cultured islets had an increased number of immature secretory granules in the
      beta cells. The number of degranulated beta cells in > 250 and < 125 microm
      cultured islets from fa/fa rats was higher than in lean rat islets (33 vs 25%).
      The glucose EC50 values for cultured islets were 4.64 +/- 0.43, 7.9 +/- 0.70 and
      7.29 +/- 1.64 mmol.l(-1) for > 250 microm, < 125 microm, and lean groups,
      respectively. Inhibition of insulin secretion by 10 mmol.l(-1) mannoheptulose was
      reduced by 50% in > 250 microm islets compared with small islets. Studies of
      individual beta cells by reverse hemolytic plaque assay revealed 3-fold more
      cells from > 250 microm islets were stimulated by 1.4 mmol.l(-1) glucose than
      cells from < 125 microm islets. We conclude that functional defects in mixed size
      populations of islets from fa/fa rats are mainly due to alterations in the large
      islets, whereas smaller islets have relatively normal function. Exposure to high
      glucose exacerbates morphological and functional differences of large islets,
      which could have important implications in the transition to noninsulin-dependent
      diabetes when beta cell insulin production is unable to compensate for
      hyperglycemia.

PMID- 9548216
TI  - Age-related loss of calcitriol stimulation of phosphoinositide hydrolysis in rat
      skeletal muscle.
AB  - We have examined the effects in vitro of calcitriol [1,25(OH)2D3], the hormonal
      form of vitamin D3, on the breakdown of membrane phosphoinositides in skeletal
      muscle from young (3 months) and aged (24 months) rats. Calcitriol (10(-9) M)
      induced a rapid and transient release of IP3/inositol phosphates and
      diacylglycerol (DAG) from muscle slices/membranes prelabeled with [3H]myo
      inositol and [3H]arachidonate, respectively. Inositol phosphate release was
      maximal at 15 s and then declined. The effects of hormone specificity exhibited
      as the closely related derivatives of vitamin D3, 25OHD3, 1alphaOHD3 and
      24,25(OH)2D3 did not alter muscle inositol phosphate levels. The stimulation of
      DAG was biphasic, the early phase (15 s) being abolished by neomycin (0.5 mM), an
      inhibitor of phosphoinositide hydrolysis, similar to IP3 formation and consistent
      with a role of phospholipase C (PLC) in intracellular signal generation. Neomycin
      had no effect on the second DAG peak (2 min) induced by calcitriol, suggesting
      that the late phase of DAG formation is independent from the hydrolysis of
      phosphoinositides. Higher basal inositol phosphate and DAG levels were detected
      in muscle from aged rats thereby reducing the effects of the hormone on second
      messenger generation ( -80 and -60% for IP3 and DAG, respectively). Calcitriol
      stimulation of PLC was mimicked, in both young and old rats, by GTPgammaS, a non
      hydrolyzable analogue of GTP, while GDPbetaS, a G protein inhibitor, suppressed
      the effect of the hormone. The early effects of calcitriol and GTPgammaS were not
      additive. Bordetella pertussis toxin abolished by 85% the effects of calcitriol
      on inositol phosphate release in young rats but was without effect in aged
      animals. These results demonstrate that calcitriol activates phosphoinositide-PLC
      in rat skeletal muscle by a mechanism which involves a pertussis-sensitive G
      protein and that the effects of the hormone are altered with ageing.

PMID- 9548218
TI  - Molecular cloning of a cDNA encoding molt-inhibiting hormone of the crab, Cancer
      magister.
AB  - A neuropeptide molt-inhibiting hormone (MIH) negatively regulates crustacean
      molting glands (Y-organs). We report here the molecular cloning of a cDNA
      encoding putative MIH of the Dungeness crab, Cancer magister. A cDNA library was
      commercially prepared using poly (A+) RNA isolated from C. magister eyestalk
      neural ganglia. The library was screened using as probe a previously cloned
      portion of a cDNA encoding MIH of the blue crab, Callinectes sapidus. DNA
      sequence analysis of one positive clone revealed a 339 base pair open reading
      frame encoding a 78 amino acid putative MIH and a 35 amino acid signal peptide.
      The deduced amino acid sequence of C. magister MIH shows high sequence identity
      (80-98%) with MIH of three other brachyuran crabs, but lower identity (26-45%)
      with MIH and MIH-like peptides from astacurans and shrimp. Studies using reverse
      transcription-polymerase chain reaction (RT-PCR) indicate the MIH gene is
      expressed in eyestalk but not control (muscle, gill, gonad, hepatopancreas)
      tissue.

PMID- 9548217
TI  - Ontogeny and epithelial-stromal interactions regulate IGF expression in the ovine
      mammary gland.
AB  - Although the insulin-like growth factors (IGF-I and -II) have been implicated in
      the stimulation of mammogenesis, little is known of their regulation in the
      mammary gland. In this study we removed epithelial tissue from one of the two
      mammary glands of 1-week-old ewe lambs and examined IGF-I and -II mRNA expression
      during postnatal development in both the intact mammary gland and in the gland
      cleared of epithelial tissue. Expression of IGF-I mRNA was highest at 6 and 10
      weeks of age, coincident with the prepubertal phase of rapid mammary growth, then
      declined and remained low until expression increased during late pregnancy. IGF-I
      mRNA was more abundant in the mammary fat pad adjacent to parenchyma (MFP) than
      in the contralateral fat pad that had been surgically cleared of epithelium
      (CFP). The level of IGF-II mRNA in parenchyma was highest at 1-23 weeks of age
      due to an increase in the abundance of specific mRNAs. Expression was lower in
      the fat pads, with generally higher levels in the intact MFP than the CFP, and in
      these tissues IGF-II expression was shown to increase with age between 6 and 23
      weeks. We also investigated the influence of the ovary and estrogen on the
      expression of IGFs. While IGF-I mRNA abundance was unaffected by ovariectomy,
      exogenous estrogen resulted in higher levels of expression in the MFP of
      ovariectomized ewes and tended to increase its level in the parenchyma of intact
      ewes. Ovariectomy increased IGF-II mRNA within mammary parenchyma whereas
      estrogen suppressed levels in both the parenchyma and MFP. These findings
      demonstrate that IGF-I and -II mRNAs are expressed locally within the developing
      ovine mammary gland and are regulated by stage of ontogeny, ovarian hormones, and
      epithelial stromal interaction.

PMID- 9548219
TI  - Zinc chelation enhances thyroid hormone induction of growth hormone mRNA in GH3
      cells.
AB  - The effects of restriction and addition of zinc on thyroid hormone responsiveness
      of the growth hormone gene were investigated in GH3, rat pituitary tumor cells.
      Addition of diethylenetriaminepenta-acetic acid (DTPA), a membrane-impermeable
      chelator, resulted in up to 10-fold increases in GH mRNA in the presence of 10 nM
      T3, with half-maximal induction at 50 microM DTPA. Only minor effects were seen
      in the absence of T3. Addition of zinc inhibited the stimulatory effect of DTPA
      in a dose-dependent manner. Equimolar concentrations of other divalent cations
      could not substitute for zinc, though inhibitions of the DTPA effect were
      observed at higher concentrations. In the absence of DTPA, exogenous zinc (100
      microM) inhibited T3-induced GH mRNA by approximately 33%. Addition of DTPA or
      zinc did not affect T3 binding to its nuclear receptor. DTPA also enhanced the
      stimulatory effect of dexamethasone on GH mRNA. The results demonstrate that
      restricted zinc availability positively affects T3 induction of the GH gene in
      GH3 cells.

PMID- 9548220
TI  - Epilepsy and learning disabilities--a challenge for the next millennium?
AB  - People with learning disabilities often have seizures in addition to other
      disorders. Precise diagnosis may be difficult, but accuracy can be improved using
      electroencephalographic and video investigations. Following the establishment of
      a diagnosis of epilepsy, individually tailored care is necessary taking into
      account other health, behavioural and therapeutic issues. Neuroimaging may
      indicate a need for surgery which should not be automatically excluded as a
      treatment option. Rational antiepileptic drug use is advised, with emphasis upon
      the newer agents due to their better tolerance and ease of use. A programme of
      regular review will prevent over-medicating. Drug therapy may be withdrawn in a
      seizure-free patient. Realistic goals should be established for each individual
      coupled with an optimistic approach to care. However, future developments require
      a solid evidence base combined with rationality in all aspects of management. The
      community learning disability epilepsy nurse specialist is the key health-care
      professional who can ensure that a learning disabled individual with epilepsy is
      able to take full advantage of all available services. Education, closer
      collaboration and the mutual recognition of skills will ensure more cohesive and
      comprehensive care for this disadvantaged patient population.

PMID- 9548221
TI  - Amnesia in temporal lobectomy patients: historical perspective and review.
AB  - Profound memory loss is a rare but serious complication of temporal-lobe surgery
      for the relief of medically intractable epilepsy. This paper examines the
      characteristics of the patients who have been reported to become amnesic
      following temporal-lobe surgery over the last four decades. The critical role of
      the hippocampi in memory function are implicated in autopsy studies and MRI
      investigations, but these cases suggest that a range of memory impairments result
      from bilateral hippocampal damage, rather than a pure amnesic syndrome in every
      case. There is some evidence that bilateral structural hippocampal abnormalities
      may not necessarily be associated with significant memory problems, if these
      abnormalities have a developmental basis. However, whilst not necessarily
      profound, any post-operative deterioration in memory function remains a
      significant consideration in the presurgical evaluation of temporal-lobe epilepsy
      patients.

PMID- 9548222
TI  - Treatment of epilepsy following rejection of epilepsy surgery.
AB  - Important progress has been made with the development of both surgical and
      medicinal treatment of epilepsy but these two developments are rarely seen in a
      common perspective. Today epilepsy surgery should be discussed with the patient
      when a reasonable degree of pharmacoresistance has been established, and the
      chances of an operation clearly outweigh its risks. At that time, there will
      still be a number of pharmacological options. A study of 15 patients who were
      evaluated for at least four years after surgery had been considered but rejected
      after intensive monitoring, pharmacological pursuit was successful in eight, and
      failed in seven. The successfully treated patients comprise three who became
      seizure free, and one with isolated auras as the only persisting seizure type.
      The successful regimens were highly individual, stretching from monotherapies to
      one four-drug combination. The idea of presenting this small series is not to
      promote or establish any therapeutic strategies and guidelines but, rather, to
      draw attention to a neglected interface between surgical and medicinal
      procedures, and to increase awareness that epilepsy therapy will still be most
      successful when it is seen as a whole, and must not be split up into competing
      ideologies. Concerns are not well founded that epilepsy surgery may be seen as
      the last hope for pharmacoresistant patients, and that, if surgery is declined, a
      loss of this hope may be intolerable to the patient.

PMID- 9548223
TI  - Juvenile myoclonic epilepsy: clinical characteristics, treatment and prognosis in
      a Norwegian population of patients.
AB  - Forty-three patients with juvenile myoclonic epilepsy (JME) is presented. The
      female to male ratio was 2.9:1. The patients answered a standardized
      questionnaire pertaining to social situation, medical history, onset of epilepsy,
      types and frequency of seizures, treatment, experienced control over seizures and
      consequences of having epilepsy. Myoclonic jerks, which are the hallmark of the
      condition, are often forgotten by the patients or not considered as epileptic
      seizures. This could be one reason why JME still seems underdiagnosed. JME may
      comprise absence, myoclonic and generalized tonic-clonic seizures (GTCS),
      proposed to occur in age-related sequence. We found that absence seizures may
      start after onset of other seizures. Our results confirm the need for medication
      since, during the last year, only 7% were seizure free without medication. Of
      patients on antiepileptic drugs (AEDs), 79.5% had no GTCS and 41% were seizure
      free during the last year, which confirms a relatively good response to
      appropriate treatment. Although most patients used AED daily and many still had
      one or more types of epileptic seizure, the epilepsy in general had very little
      impact on their lives.

PMID- 9548224
TI  - Interictal quantitative EEG in epilepsy.
AB  - The interictal EEG is often normal in epilepsy patients, particularly with
      partial seizures of extratemporal origin. Quantitative techniques of EEG analysis
      may increase the yield of diagnostic abnormality in such patients. Thirty
      patients with partial seizures of frontal or temporal origin had EEG recorded
      from left frontal (F7-C3), right frontal (F8-C4), left posterior (T5-O1), and
      right posterior (T6-O2) derivations. Four-second epochs were used to compute
      power in the delta (0.25-4.0 Hz), theta (4.25-8.0 Hz), alpha (8.25-13 Hz), and
      beta (13.25-30 Hz) bands. The ratio of high (8.25-30 Hz) to low (0.25-8 Hz) power
      on the left and the right was measured, as was the ratio between the left and the
      right hemisphere total power. The mean frequency deviation in the alpha band
      between the left and the right hemispheres was also measured, and spectral
      mobility was determined in the right and the left frontal regions. These values
      were also calculated in normal subjects and tension headache patients with normal
      EEGs. Seizure patients with abnormal interictal EEGs had decreased ratios of high
      to low power, greater asymmetry of total power and alpha frequency, and reduced
      spectral mobility on the side of their EEG foci. Epileptics with normal
      interictal EEGs had lower ratios of high to low power, greater alpha frequency
      asymmetry, and lower spectral mobility than did headache patients or normal
      controls. Power and frequency measurements, and determination of spectral
      measures such as mobility, can be done with commercially available digital EEG
      equipment. They may demonstrate otherwise obscure asymmetries in the interictal
      EEG and thereby aid in epilepsy diagnosis and classification.

PMID- 9548225
TI  - Clinical observations of juvenile myoclonic epilepsy in 131 patients: a study in
      South India.
AB  - We studied clinical features of 131 patients with juvenile myoclonic epilepsy
      (JME). The prevalence was 7.7% among the epileptic patients registered. The mean
      age at onset was 13.37+/-4.93 years and the diagnosis was established at a mean
      age of 19.53+/-7.85 years. Absence seizures were reported by 27 (20.6%) patients,
      myoclonic jerks by 131 (100%) and generalized tonic-clonic seizures (GTCS) by 111
      (84.7%). The triad of absence seizures, myoclonic jerks and GTCS was noted in 23
      (17.5%) patients, 88 (67.2%) had myoclonic jerks and GTCS, 4 (3%) had absence
      seizures and myoclonic jerks and 16 (12.2%) had only myoclonic jerks. Early onset
      absences were seen in 21 (16%) patients and the onset was late in 6 (4.6%).
      Absences antedated other types of seizures in all the patients. Myoclonic jerks
      were predominantly unilateral or had unilateral onset in 22 (16.8%). In 17 (13%)
      patients GTCS antedated myoclonic jerks. Myoclonic jerks had characteristic
      circadian distribution in 112 (85.5%) patients. On awakening GTCS occurred in 87
      (78.4%) patients and in 4 (3.6%) patients they were purely nocturnal. Sleep
      deprivation was the most important precipitating factor (54.2%). Initial
      electroencephalogram (EEG) showed classical generalized spike or multiple-spike
      slow-wave paroxysms in 81% of records. Focal EEG abnormalities were noted in
      20.6% of records. The most common focal abnormality was voltage asymmetry. A
      family history of epilepsy was noted in 31 (23.6%) probands. Diagnosis of JME was
      made in all the cases in the clinic. The factors responsible for delay in
      diagnosis of the 36 patients seen by neurologists included failure to ask or
      interpret the history which was otherwise suggestive of myoclonic jerks in all 36
      (100%) cases, the type of seizure for which the patients sought medical
      attention, and misinterpretation of EEGs in 28 patients. Diagnosis of partial
      epilepsy was made in seven patients. The factors responsible for such diagnoses
      were, unilateral jerks in one patient, unilateral jerks and absence seizures in
      three patients and focal EEG abnormalities in three patients.

PMID- 9548226
TI  - Epilepsy, cerebral calcifications and clinical or subclinical coeliac disease.
      Course and follow up with gluten-free diet.
AB  - We have studied four patients (three male, one female, age range 15-25 years)
      with epilepsy, bilateral occipital calcifications and latent coeliac disease
      (CD). The epilepsy started at mean age 7 years, in three cases there were partial
      seizures and in one case generalized seizure. Three cases had symptoms suggesting
      malabsorptive syndrome during infancy and one case was diagnosed CD before the
      onset of seizures. In all cases serologic markers of CD were found, especially
      antiendomisium antibody, and intestinal biopsy indicated several grades of
      atrophy. The electroencephalograph (EEG) findings pointed to focal abnormalities
      in three patients and generalized abnormalities in one patient. In all cases
      computer tomography (CT) showed bilateral, almost symmetrical occipital
      calcifications in the cortical subcortical layers. The enhanced CT were
      unremarkable and magnetic resonance images (MRI) were normal. After diagnosis of
      CD, all patients followed a gluten-free diet and in three patients a significant
      reduction in seizure frequency was observed. CD should be ruled out in all cases
      of epilepsy, cerebral calcifications of unexplained origin and malabsorption
      syndrome in infancy.

PMID- 9548227
TI  - Gabapentin add-on therapy with adaptable dosages in 610 patients with partial
      epilepsy: an open, observational study. The French Gabapentin Collaborative
      Group.
AB  - The objectives were to evaluate gabapentin add-on therapy in a large population
      under conditions close to real practice and to determine the therapeutic doses as
      reached with adaptable dosages. A 6-month multicentre, open-label study, involved
      addition of gabapentin to pre-existing treatment at the initial dosage of 1200 mg
      and subsequent adjustment between 900 and 2400 mg/day according to efficacy and
      tolerability. A study group of 610 adult patients, with partial epilepsy,
      persistent seizures and a median seizure frequency with a baseline of 7.2 per
      month were recruited; one-third had less than four seizures per month.
      Polypharmacy was frequent, with a mean of 2.3 concomitant drugs. After 6 months,
      368 patients (62%) continued on gabapentin, at a mean dosage of 1739 mg/day with
      44% of responders. On an intention-to-treat basis, median reduction in frequency
      was 21.2%, and the responder rate was 33.9%. The responder rate increased to
      40.7% in the less severe subgroup receiving only one concomitant drug. Seventy
      nine patients (13.4%) remained without seizures during the last evaluation
      period, versus nine (1.5%) during the baseline. Most of them had initially less
      than four seizures per month. The most frequent adverse effects, somnolence
      (29.3%), asthenia (14.6%), nausea (7.9%), ataxia (7.7%) and vertigo (7.2%),
      occurred rapidly after initial titration to 1200 mg/day, and were usually
      transitory. Weight gain (8.8%) seemed to be related to gabapentin dose. The
      combination of two recent drugs, vigabatrin and gabapentin, in 190 patients led
      to similar efficacy levels, with a tendency for more frequent somnolence and
      asthenia.

PMID- 9548228
TI  - Misdiagnosis and treatment in juvenile myoclonic epilepsy.
AB  - Of 1300 epileptic patients 76 (5.8%) were found to have juvenile myoclonic
      epilepsy (JME). These 76 patients were examined at the epilepsy outpatient clinic
      of Bakirkoy State Hospital for Neurological and Psychiatric Diseases between 1991
      and 1996 and data obtained were analysed retrospectively. Clinically typical
      absence seizures were reported in 40.8%, myoclonic jerks in 100%, and generalized
      tonic-clonic seizures in 82.9% of the patients. Neurological and mental
      examination was normal for all patients with the exception of three cases; two
      with essential tremor and one with minimal dysarthria. Precipitating factors were
      noted in 85.5% of cases. Abnormal EEG was recorded in 73 (6.1%) patients.
      Abnormalities mainly consisted of generalized discharges of spike/polyspike and
      slow-wave (86.6%) and generalized paroxysmal theta or delta (9.2%). Fifteen
      (19.7%) had focal abnormalities and 20 (26.4%) had photoconvulsive discharges. Of
      the 76 patients, 40 (52.6%) were not diagnosed at the initial interview; definite
      diagnosis was delayed by a mean of 5.9 years. As a result of misdiagnosis at the
      initial interview 40 patients had been administered AED except for valproate.
      After reassessment of clinical and EEG findings, the medication was changed to
      valproate therapy. As a result, 65 of our JME patients (85.5%) were seizure free
      after a one-year follow-up period.

PMID- 9548229
TI  - Episodic nocturnal wandering and complex visual hallucination. A case with long
      term follow-up.
AB  - Episodic nocturnal wandering is rare and thought to be an atypical form of
      nocturnal epilepsy which is responsive to anticonvulsant therapy. We report a
      case of adult-onset episodic sleep-walking and daytime complex visual
      hallucination. Ambulatory EEG recordings suggested that both events were ictal
      phenomenon. Interictal sphenoidal EEG and SPECT studies revealed an epileptogenic
      focus in the left anterior temporal lobe. During the nocturnal wanderings, the
      patient had bizarre but non-violent behaviour, and was at risk of minor or severe
      injury to himself. Both events were completely controlled by carbamazepine for a
      follow-up period of 8 years. The present case further supports the notion that
      episodic nocturnal wandering represents an unusual type of nocturnal complex
      partial seizures.

PMID- 9548230
TI  - Injury-induced physiological events that may modulate gene expression in neurons
      and glia.
AB  - Damage to the brain triggers a host of reactive responses in neurons and glia
      which are seen at sites of focal injury as well as at sites that are at a
      distance from the injury. Although many of these responses have been studied
      extensively, the signals that initiate the different responses have not been
      fully characterized, and it is still not understood how focal injury affects
      neurons and glia in distant sites. The present review summarizes recent findings
      that suggest that physiological events that occur at the time of the injury or
      during the early postlesion period can play an important and variable role in
      modulating neuronal and glial responses to injury. We focus on the events that
      occur in the hippocampal formation following unilateral lesions of the entorhinal
      cortex - a model system that has been used extensively for studies of cellular
      responses following focal brain injury. This lesion destroys the cells of origin
      of a massive excitatory projection to the dentate gyrus and hippocampus proper.
      Over time, the denervated neurons in the hippocampal formation are almost
      completely reinnervated as a result of local sprouting of systems that survive
      the lesion. Thus, this model system has been useful for studying cellular
      responses to both denervation and reinnervation. We summarize the information
      that this injury triggers physiological events that can strongly modulate gene
      expression in neurons and glia, including episodes of spreading depression that
      occur at the time of the injury, seizures that occur during the early postlesion
      period, the loss of afferent drive which leads to decreases in postsynaptic
      activity, and the restoration of activity that occurs in conjunction with
      reinnervation. We describe recent studies which suggest that some of these
      physiological events occur to a variable extent in different animals, especially
      the episodes of spreading depression and the recurrent seizures. Thus, the
      spatial pattern and temporal dynamics of altered gene expression following this
      "model" experimental injury may vary from animal to animal. The fact that
      physiological events strongly modulate the reactive changes in gene expression
      that occur following injury has important implications for understanding the
      sequelae of injury, and offers new opportunities for experimental and therapeutic
      interventions that may improve cellular repair, regeneration, and recovery of
      function.

PMID- 9548231
TI  - Two forms of hippocampal long-term depression, the counterpart of long-term
      potentiation.
AB  - In the hippocampus there are two distinct forms of long-term depression (LTD) of
      excitatory synaptic transmission. In the CA1 region, prolonged low-frequency
      stimulation induces LTD by activating postsynaptic NMDA receptors, which causes a
      moderate rise in Ca2+ concentrations. In mossy fiber synapses of the CA3 region,
      similar low-frequency stimulation also gives rise to LTD. However, this form of
      LTD (mossy fiber LTD) does not require activation of NMDA receptors, but is
      mediated by activation of presynaptic metabotropic glutamate receptors. Induction
      of mossy fiber LTD is not dependent on postsynaptic depolarization or activation
      of postsynaptic ionotropic glutamate receptors, thus it is likely to be mediated
      by purely presynaptic mechanisms. This conclusion is confirmed by the analysis of
      mutant mice lacking presynaptic mGluR2, in which mossy fiber LTD is almost
      absent. Since long-term potentiation at mossy fiber synapses is also induced
      presynaptically, the synaptic efficacy may be regulated through common mechanisms
      bidirectionally, which may contribute to neural information processing in the
      hippocampus.

PMID- 9548232
TI  - The neuroregulatory properties of L-DOPA. A review of the evidence and potential
      role in the treatment of Parkinson's disease.
AB  - Accumulating evidence suggests that L-dihydroxyphenylalanine (L-DOPA) has
      neurotransmitter-like and/or neuromodulatory properties in the CNS. Such evidence
      is based on a wide range of findings including the existence of specific L
      DOPAergic neurons in several regions of the CNS, neurotransmitter-like
      characteristics and specific pharmacological effects. This review attempts to
      outline the main evidence for this conception and to relate such findings to L
      DOPA treatment effects in Parkinson's disease. In this context L-DOPA in itself
      has been shown to potentiate D2 receptor-mediated effects, inhibit acetylcholine
      release and increase the release of L-glutamate, neuropharmacological effects
      which can be linked to treatment side-effects in advanced Parkinson's disease. It
      is suggested that supersensitive L-DOPA-mediated effects contribute to the
      pathogenesis underlying L-DOPA-induced motor complications in advanced
      Parkinson's disease. However, since specific L-DOPA receptors have yet to be
      identified, the assessment of the relative importance of L-DOPA-mediated effects
      in this clinical context must be regarded as incomplete.

PMID- 9548233
TI  - The basis of the neural organization for language: evidence from sign language
      aphasia.

PMID- 9548234
TI  - Apoptosis, neurotrophic factors and neurodegeneration.
AB  - Apoptosis is an active process of cell death characterized by distinct
      morphological features, and is often the end result of a genetic programme of
      events, i.e. programmed cell death (PCD). There is growing evidence supporting a
      role for apoptosis in some neurodegenerative diseases. This conclusion is based
      on DNA fragmentation studies and findings of increased levels of pro-apoptotic
      genes in human brain and in in vivo and in vitro model systems. Additionally,
      there is some evidence for a loss of neurotrophin support in neurodegenerative
      diseases. In Alzheimer's disease, in particular, there is strong evidence from
      human brain studies, transgenic models and in vitro models to suggest that the
      mode of nerve cell death is apoptotic. In this review we describe the evidence
      implicating apoptosis in neurodegenerative diseases with a particular emphasis on
      Alzheimer's disease.

PMID- 9548235
TI  - Support for a pragmatic health minister.

PMID- 9548237
TI  - Africa defends rights to indigenous knowledge.

PMID- 9548236
TI  - Legal fight looms over patent bid on human/animal chimaeras.

PMID- 9548238
TI  - Neuroscientist accused of misconduct turns on his accusers.

PMID- 9548239
TI  - Scientists defy their ethics codes and take gifts from industry.

PMID- 9548240
TI  - Ageing population of voters backs Alzheimer's funding.

PMID- 9548241
TI  - Coalition to pursue ethnic concerns over gene research.

PMID- 9548242
TI  - Scapegoat for fraud in Germany?

PMID- 9548243
TI  - AIDS therapy in Brazil.

PMID- 9548244
TI  - A sense of direction.

PMID- 9548245
TI  - Molecular endocrinology. Steroids tickle cells inside and out.

PMID- 9548246
TI  - Biomathematics. Merging lines and emerging levels.

PMID- 9548247
TI  - Apoptosis. Phagocytic docking without shocking.

PMID- 9548248
TI  - Domains of rasGAP and rhoGAP are related.

PMID- 9548249
TI  - Support for shared ancestry of GAPs.

PMID- 9548250
TI  - Meningitis bacterium is viable without endotoxin.

PMID- 9548251
TI  - Speed perception fogs up as visibility drops.

PMID- 9548253
TI  - Cerebellar complex spikes encode both destinations and errors in arm movements.
AB  - Purkinje cells of the cerebellum discharge complex spikes, named after the
      complexity of their waveforms, with a frequency of approximately 1 Hz during arm
      movements. Despite the low frequency of firing, complex spikes have been proposed
      to contribute to the initiation of arm movements or to the gradual improvement of
      motor skills. Here we recorded the activity of Purkinje cells from the hemisphere
      of cerebellar lobules IV-VI while trained monkeys made short-lasting reaching
      movements (of approximately 200 milliseconds in duration) to touch a visual
      target that appeared at a random location on a tangent screen. We examined the
      relationship between complex-spike discharges and the absolute touch position,
      and between complex-spike discharges and relative errors in touching the screen.
      We used information theory to show that the complex spikes occurring at the
      beginning of the reach movement encode the absolute destination of the reach, and
      the complex spikes occurring at the end of the short-lasting movements encode the
      relative errors. Thus, complex spikes convey multiple types of information,
      consistent with the idea that they contribute both to the generation of movements
      and to the gradual, long-term improvement of these movements.

PMID- 9548252
TI  - Light-driven production of ATP catalysed by F0F1-ATP synthase in an artificial
      photosynthetic membrane.
AB  - Energy-transducing membranes of living organisms couple spontaneous to non
      spontaneous processes through the intermediacy of protonmotive force (p.m.f.)--an
      imbalance in electrochemical potential of protons across the membrane. In most
      organisms, p.m.f. is generated by redox reactions that are either photochemically
      driven, such as those in photosynthetic reaction centres, or intrinsically
      spontaneous, such as those of oxidative phosphorylation in mitochondria.
      Transmembrane proteins (such as the cytochromes and complexes I, III and IV in
      the electron-transport chain in the inner mitochondrial membrane) couple the
      redox reactions to proton translocation, thereby conserving a fraction of the
      redox chemical potential as p.m.f. Many transducer proteins couple p.m.f. to the
      performance of biochemical work, such as biochemical synthesis and mechanical and
      transport processes. Recently, an artificial photosynthetic membrane was reported
      in which a photocyclic process was used to transport protons across a liposomal
      membrane, resulting in acidification of the liposome's internal volume. If
      significant p.m.f. is generated in this system, then incorporating an appropriate
      transducer into the liposomal bilayer should make it possible to drive a non
      spontaneous chemical process. Here we report the incorporation of F0F1-ATP
      synthase into liposomes containing the components of the proton-pumping
      photocycle. Irradiation of this artificial membrane with visible light results in
      the uncoupler- and inhibitor-sensitive synthesis of adenosine triphosphate (ATP)
      against an ATP chemical potential of approximately 12 kcal mol(-1), with a
      quantum yield of more than 7%. This system mimics the process by which
      photosynthetic bacteria convert light energy into ATP chemical potential.

PMID- 9548254
TI  - Synaptic vesicles retain their identity through the endocytic cycle.
AB  - After fusion of synaptic vesicles with presynaptic membrane and secretion of the
      contents of the vesicles into the synaptic cleft (a process known as exocytosis),
      the vesicular membrane is retrieved by endocytosis (internalization) for re-use.
      Several issues regarding endocytosis at central synapses are unresolved,
      including the location of membrane retrieval (relative to the active zone, where
      exocytosis occurs), the time course of various endocytic steps, and the recycling
      path taken by newly endocytosed membranes. The classical model of synaptic
      vesicle recycling, proposed by analogy to other cellular endocytic pathways,
      involves retrieval of the membrane, fusion of the membrane with endosome-like
      compartments and, finally, budding of new synaptic vesicles from endosomes,
      although the endosomal station may not be obligatory. Here we test the classical
      model by using the fluorescent membrane dye FM1-43 with quantitative fluorescence
      microscopy. We find that the amount of dye per vesicle taken up by endocytosis
      equals the amount of dye a vesicle releases on exocytosis; therefore, we conclude
      that the internalized vesicles do not, as the classical picture suggests,
      communicate with intermediate endosome-like compartments during the recycling
      process.

PMID- 9548255
TI  - C. elegans phagocytosis and cell-migration protein CED-5 is similar to human
      DOCK180.
AB  - During programmed cell death, cell corpses are rapidly engulfed. This engulfment
      process involves the recognition and subsequent phagocytosis of cell corpses by
      engulfing cells. How cell corpses are engulfed is largely unknown. Here we report
      that ced-5, a gene that is required for cell-corpse engulfment in the nematode
      Caenorhabditis elegans, encodes a protein that is similar to the human protein
      DOCK180 and the Drosophila melanogaster protein Myoblast City (MBC), both of
      which have been implicated in the extension of cell surfaces. ced-5 mutants are
      defective not only in the engulfment of cell corpses but also in the migrations
      of two specific gonadal cells, the distal tip cells. The expression of human
      DOCK180 in C. elegans rescued the cell-migration defect of a ced-5 mutant. We
      present evidence that ced-5 functions in engulfing cells during the engulfment of
      cell corpses. We suggest that ced-5 acts in the extension of the surface of an
      engulfing cell around a dying cell during programmed cell death. We name this new
      family of proteins that function in the extension of cell surfaces the CDM (for
      CED-5, DOCK180 and MBC) family.

PMID- 9548256
TI  - Human CD14 mediates recognition and phagocytosis of apoptotic cells.
AB  - Cells undergoing programmed cell death (apoptosis) are cleared rapidly in vivo by
      phagocytes without inducing inflammation. Here we show that the
      glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 on the
      surface of human macrophages is important for the recognition and clearance of
      apoptotic cells. CD14 can also act as a receptor that binds bacterial
      lipopolysaccharide (LPS), triggering inflammatory responses. Overstimulation of
      CD14 by LPS can cause the often fatal toxic-shock syndrome. Here we show that
      apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic
      cells. This interaction depends on a region of CD14 that is identical to, or at
      least closely associated with, a region known to bind LPS. However, apoptotic
      cells, unlike LPS, do not provoke the release of pro-inflammatory cytokines from
      macrophages. These results indicate that clearance of apoptotic cells is mediated
      by a receptor whose interactions with 'non-self' components (LPS) and 'self'
      components (apoptotic cells) produce distinct macrophage responses.

PMID- 9548257
TI  - Inhibition of oxytocin receptor function by direct binding of progesterone.
AB  - The steroid hormone progesterone (P4) is essential for establishing and
      maintaining pregnancy in mammals. One of its functions includes maintenance of
      uterine quiescence by decreasing uterine sensitivity to the uterotonic peptide
      hormone oxytocin. Although it is generally held that steroid hormones such as P4
      act at a genomic level by binding to nuclear receptors and modulating the
      expression of specific target genes, we show here that the effect of P4 on
      uterine sensitivity to oxytocin involves direct, non-genomic action of P4 on the
      uterine oxytocin receptor (OTR), a member of the G-protein-coupled receptor
      family. P4 inhibits oxytocin binding to OTR-containing membranes in vitro, binds
      with high affinity to recombinant rat OTR expressed in CHO cells, and suppresses
      oxytocin-induced inositol phosphate production and calcium mobilization. These
      effects are highly steroid- and receptor-specific, because binding and signalling
      functions of the closely related human OTR are not affected by P4 itself but by
      the P4 metabolite 5beta-dihydroprogesterone. Our findings provide the first
      evidence for a direct interaction between a steroid hormone and a G-protein
      coupled receptor and define a new level of crosstalk between the peptide- and
      steroid-hormone signalling pathways.

PMID- 9548258
TI  - Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4alpha.
AB  - Dietary fatty acids specifically modulate the onset and progression of various
      diseases, including cancer, atherogenesis, hyperlipidaemia, insulin resistances
      and hypertension, as well as blood coagulability and fibrinolytic defects; their
      effects depend on their chain length and degree of saturation. Hepatocyte nuclear
      factor-4alpha (HNF-4alpha) is an orphan transcription factor of the superfamily
      of nuclear receptors and controls the expression of genes that govern the
      pathogenesis and course of some of these diseases. Here we show that long-chain
      fatty acids directly modulate the transcriptional activity of HNF-4alpha by
      binding as their acyl-CoA thioesters to the ligand-binding domain of HNF-4alpha.
      This binding may shift the oligomeric-dimeric equilibrium of HNF-4alpha or may
      modulate the affinity of HNF-4alpha for its cognate promoter element, resulting
      in either activation or inhibition of HNF-4alpha transcriptional activity as a
      function of chain length and the degree of saturation of the fatty acyl-CoA
      ligands. In addition to their roles as substrates to yield energy, as an energy
      store, or as constituents of membrane phospholipids, dietary fatty acids may
      affect the course of a disease by modulating the expression of HNF-4alpha
      controlled genes.

PMID- 9548259
TI  - Dual function of the messenger RNA cap structure in poly(A)-tail-promoted
      translation in yeast.
AB  - The messenger RNA 3' poly(A) tail critically affects the initiation and control
      of translation in eukaryotes. By analogy to elements involved in transcription
      initiation, the poly(A) tail has been described as a 'translational enhancer'
      that enhances the 'translational promoter' activity of the mRNA 5'-cap structure.
      Elongation or shortening of the poly(A) tail regulates translation during
      development. Here we show, using cell-free and in vivo translation analyses in
      Saccharomyces cerevisiae, that the poly(A) tail can act as an independent
      'translational promoter', delivering ribosomes to uncapped mRNAs even if their 5'
      end is blocked. When mRNAs compete for ribosome binding, neither the cap
      structure nor the poly(A) tail alone is enough to drive efficient translation,
      but together they synergize and direct ribosome entry to the 5' end. The cap
      structure both promotes ribosome recruitment, together with the poly(A) tail, and
      tethers recruited ribosomes to the 5' end. Correct choice of translation
      initiation codons and the function of translational regulators acting on the 5'
      untranslated region are thus ensured by the functional interaction of the poly(A)
      tail with the cap structure.

PMID- 9548260
TI  - Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP
      enhances translation.
AB  - In the initiation of translation in eukaryotes, binding of the small ribosomal
      subunit to the messenger RNA results from recognition of the 5' cap structure
      (m7GpppX) of the mRNA by the cap-binding complex eIF4F. eIF4F is itself a three
      subunit complex comprising the cap-binding protein eIF4E, eIF4A, an ATP-dependent
      RNA helicase, and eIF4G, which interacts with both eIF4A and eIF4E and enhances
      cap binding by eIF4E. The mRNA 3' polyadenylate tail and the associated poly(A)
      binding protein (PABP) also regulate translational initiation, probably by
      interacting with the 5' end of the mRNA. In yeast and plants, PABP interacts with
      eIF4G but no such interaction has been reported in mammalian cells. Here, we
      describe a new human PABP-interacting protein, PAIP-I, whose sequence is similar
      to the central portion of eIF4G and which interacts with eIF4A. Overexpression of
      PAIP-1 in COS-7 cells stimulates translation, perhaps by providing a physical
      link between the mRNA termini.

PMID- 9548261
TI  - Signal transduction in hepatic stellate cells.
AB  - Hepatic stellate cells (HSC) are presently regarded as one of the key cell types
      involved in the progression of liver fibrosis and in the related
      pathophysiological and clinical complications. Following acute or chronic liver
      tissue damage, HSC undergo a process of activation towards a phenotype
      characterised by increased proliferation, motility, contractility and synthesis
      of extracellular matrix (ECM) components. Several factors have been shown to play
      a key role in the promotion of the full-blown picture of activated HSC. These
      include extensive changes in the composition and organisation of the ECM, the
      secretion of several growth factors, cytokines, chemokines, products of oxidative
      stress and other soluble factors. It is evident that each cellular response to
      extracellular stimuli must be framed in a scenario where different forces
      modulate one another and result in a prevalent biological effect. Along these
      lines, the identification and characterisation of intracellular signalling
      pathways activated by different stimuli in HSC represent a mandatory step. In
      this review article we have made an attempt to summarise recent acquisitions to
      our knowledge of the involvement of different intracellular signalling pathways
      in key aspects of HSC biology.

PMID- 9548262
TI  - Angiogenesis in hepatocellular carcinoma as evaluated by CD34
      immunohistochemistry.
AB  - To clarify the relationship between angiogenesis and hepatocarcinogenesis on
      progression of hepatocellular carcinoma (HCC), we quantitatively evaluated
      angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous
      hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67
      immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry
      using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated
      using monoclonal antibody MIB-1. We used an image analysis system to assess the
      microvessel density as the area percentage of the endothelial area. Angiogenesis
      was generally observed in HCC and there was no significant difference among all
      clinical stages and histological grades of HCC. On the other hand, the staining
      of CD34 was partly observed in sinusoids of AH, although no positive staining was
      seen in any sinusoids of LC. The proliferative activity was significantly
      correlated with the clinical stage and histological grade of HCC. Our results
      indicate that the quantitation of angiogenesis does not provide significant
      prognostic information in HCC, but that it may have diagnostic value in
      distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically
      diagnosed as cancer, shows positive staining for CD34, suggesting that some
      portion of AH contains cancerous characteristics.

PMID- 9548263
TI  - Regeneration of the hepatic nerves following surgical denervation of the liver in
      dogs.
AB  - This study was conducted to examine the regeneration process of hepatic nerves
      following surgical hepatic denervation in dogs. A denervation model was
      surgically created by removing all visible nerves around the hepatoduodenal
      ligament along with the peri-hepatic tissues. The hepatic nerves were examined on
      the hepatic specimens taken at 1 week, 1 month and 3 months post-denervation by
      means of immunohistochemical staining, and also electron microscopy. At 1 week
      post-denervation, the extrinsic hepatic nerves were observed not to have
      regenerated. However, at 1 month post-denervation, GAP-43-positive nerves were
      identified and regenerating axons were shown to be present on electron
      microscopic observation. The immunoreactivity for anti-GAP-43 antibody was not
      shown any longer at 3 months post-denervation, and the regenerated nerve axons
      were shown to be similar to those at pre-denervation on ultrastructural study.
      Results of the present study suggested that regeneration of the extrinsic hepatic
      nerves began to appear about 1 month after the hepatic denervation, and was
      completed by 3 months post-denervation.

PMID- 9548264
TI  - Autonomic nervous system activity during infusion of L-arginine in patients with
      liver cirrhosis.
AB  - Patients with liver cirrhosis exhibit a hyperdynamic circulatory state as
      evidenced by tachycardia and an increase in cardiac output accompanied by an
      elevation of sympathetic tone. This condition is due to the excessive release of
      nitric oxide (NO), an endogenous vasodilator, which is in turn related to the
      abnormal induction of NO synthase. The present study investigated whether the
      intravenous infusion of L-arginine, the precursor of NO, may cause a similar
      hyperdynamic circulatory state. A new method, the analysis of power spectrum
      heart rate variability, was used to evaluate autonomic nervous activity. Twenty
      patients with liver cirrhosis underwent continuous Holter monitoring of the ECG
      during the intravenous administration of L-arginine (10 g) (Fisher's solution)
      infused over 60 min. Power spectral analysis was computed from 512 beats of the
      Holter ECG data. Low frequency (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15
      0.40 Hz) spectral powers and the ratio of LF to HF (LF/HF) were calculated every
      10 min before and after the infusion of L-arginine. The LF power, which reflects
      sympathetic tone modified by vagal tone, and the LF/HF, an indicator of
      sympathetic tone, were both significantly increased during the infusion (p<0.05).
      HF power, an indicator of parasympathetic tone, showed no significant change in
      the early stage of the infusion but was significantly increased in the late stage
      (p<0.05). The administration of L-arginine thus led to an elevation of
      sympathetic tone. Fisher's solution, which is administered to patients with
      hepatic insufficiency, contains L-arginine, and may also produce a hyperdynamic
      circulatory state as an adverse effect related to an elevation of the plasma
      level of NO by L-arginine. The monitoring of such patients is thus indicated.

PMID- 9548265
TI  - Hepatitis C virus genotypes: epidemiological and clinical associations. Benelux
      Study Group on Treatment of Chronic Hepatitis C.
AB  - In a cohort of 292 chronic hepatitis C patients living in the Benelux countries
      the relationship between viral genotype and geographical origin, route of
      transmission, clinical characteristics and severity of liver disease was
      analyzed. HCV-RNA isolates could be classified by the Line Probe Assay (LiPA) as
      1a, 1b, 2, 3, 4 or 5 in 286 (98%) cases. Patients of European origin were
      predominantly infected with HCV subtype 1b (164/254, 65%, CI 58-70%), as were
      patients of Asian origin (7/13, 54%). Patients originating from Surinam (South
      America) had predominantly type 2 (9/10, 90%), whereas Africans were mainly
      infected with type 4 (7/9, 77%). Blood transfusion was the mode of transmission
      in 142 (50%) patients, intravenous drug abuse (IVDA) in 40 (14%), occupational
      needle accident or tattoo in 11 (4%); no obvious source of infection was found in
      93 (33%). In patients infected by blood transfusion, subtype 1b was predominant
      (70%, CI 61-77%), whereas subtypes la and 3 were predominant in those infected by
      IVDA (25% and 45%, respectively, p<0.001). Cirrhosis was observed in 68 (24%)
      patients; in multivariate analysis, factors independently related to cirrhosis
      were: the duration of infection, age and prior hepatitis B. No significant
      relationship was found between the severity of fibrosis or liver inflammation and
      the HCV (sub)types. In summary, in this large cohort of patients in the Benelux
      countries the hepatitis C virus (sub)type present was clearly related to the
      country of origin and the route of transmission, but not to the severity of liver
      disease.

PMID- 9548266
TI  - An endothelin receptor antagonist TAK-044 ameliorates carbon tetrachloride
      induced acute liver injury and portal hypertension in rats.
AB  - Hepatic levels of a powerful vasoconstrictor endothelin-1 (ET-1) and its
      receptors increase in human and carbon tetrachloride (CCl4)-induced liver
      cirrhosis. The aim of this study was to determine whether antagonism of hepatic
      ET-1 receptors ameliorates CCl4-induced hepatic injury and portal hypertension in
      rats. Acute liver injury was induced by a single intraperitoneal injection of
      CCl4 (0.3 ml/kg), whereas cirrhosis and portal hypertension were induced by CCl4
      treatment (0.15 ml/kg twice a week) for 8 weeks. Hepatic morphology, ET-1 and its
      receptors, and portal venous pressures were determined. Increases in ET-1 and its
      receptors occurred within 24 h of CCl4 administration, and progressively
      thereafter during the development of cirrhosis. The acute CCl4-induced hepatic
      injury was characterized by significant increases in portal pressure (from 8.7+/
      1.8 to 17.6+/-3.3 mmHg; p<0.01) and serum levels of liver enzymes, as well as
      massive hepatocellular necrosis (62+/-8%). Intravenous administration of an ET-1
      receptor antagonist TAK-044 reduced portal pressure to 13.6+/-2.8 mmHg (p<0.05),
      and ameliorated hepatocellular necrosis by about 35% (p<0.001). TAK-044 treatment
      also produced significant reduction in serum levels of liver enzymes. In
      cirrhotic rats, portal venous infusion of TAK-044 reduced portal hypertension by
      about 40% (p<0.05). In conclusion, these results indicate involvement of ET-1 in
      acute liver injury as well as portal hypertension associated with hepatic
      cirrhosis, and a potential for ET-1 receptor antagonists in the treatment of
      these pathologic conditions.

PMID- 9548267
TI  - Hepatitis C associated with Guillain-Barre syndrome.
AB  - Hepatitis C is frequently associated with immune-mediated diseases, such as
      cryoglobulinemia. Guillain-Barre syndrome is an acute demyelinating neuropathy of
      probable immune pathogenesis. We describe two patients with Guillain-Barre
      syndrome, and associated chronic hepatitis C, the second one previously treated
      with interferon. The link between both conditions may be hepatitis C being the
      trigger of this immune polyneuropathy. Guillain-Barre syndrome should be added to
      the list of conditions associated with hepatitis C.

PMID- 9548268
TI  - Enhancement of albumin production by hepatocyte growth factor in rat hepatocytes:
      distinction in mode of action from stimulation of DNA synthesis.
AB  - Hepatocyte growth factor (HGF) has been shown to enhance albumin production as
      well as stimulate DNA synthesis in hepatocytes. The mode of action of HGF in
      exerting both effects is to be elucidated. We previously observed that hepatocyte
      proliferation occurred in normal rats given recombinant human HGF (rhHGF)
      intravenously. When rats received rhHGF similarly, serum albumin levels were
      significantly increased compared to controls. In primary culture of rat
      hepatocytes, albumin concentration in culture medium was significantly increased
      by rhHGF added at 24 h of culture compared to controls, increasing with time of
      culture. This effect of rhHGF was dose-related. When actinomycin D was added to
      the medium, the albumin concentration was reduced in a dose-related manner, but
      its enhancement by rhHGF was maintained. Albumin mRNA levels were not increased
      by rhHGF. When rhHGF was added similarly to the medium, immunocytochemically
      positive hepatocytes for 5-bromo-2'-deoxyuridine (BrdU) incorporation appeared 30
      h later. Of these labeled hepatocytes, 12.5% were concomitantly stained for
      albumin. In contrast, albumin-positive hepatocytes were seen in 77% of BrdU-non
      labeled hepatocytes (p<0.01). We conclude that HGF may enhance albumin production
      through post-transcriptional regulation in non-proliferating hepatocytes, but not
      in proliferating hepatocytes.

PMID- 9548269
TI  - Deferoxamine arrests in vitro the proliferation of porcine hepatocyte in G1 phase
      of the cell cycle.
AB  - Iron is required for cell proliferation of all living species. Moreover, iron
      excess may be involved in the development of hepatocellular carcinoma. In this
      study we analyzed the effects of deferoxamine, an iron chelator, on normal
      porcine hepatocyte proliferation. We confirmed that hepatocytes isolated from
      young pigs proliferate in the presence of insulin and fetal calf serum as shown
      by [3H] methyl-thymidine incorporation, presence of mitotic figures and increase
      in cell number. This was paralleled by nuclear expression of p34cdc2 and its
      associated histone H1 kinase activity. In the presence of deferoxamine, [3H]
      methyl-thymidine incorporation, expression of nuclear proteins (p34cdc2 and PCNA)
      and H1 kinase activity were drastically reduced. In addition, in contrast with
      control cultures, cells in S-phase were not detected by flow cytometry. These
      data suggest that iron chelation by deferoxamine can arrest the progression of
      porcine hepatocytes in the G1 phase of the cell cycle.

PMID- 9548270
TI  - Fulminant hepatic failure associated with dicoumarol therapy.
AB  - Coumarins have been associated with non-predictable hepatic injury. In the case
      of dicoumarol, there is no hard evidence in the literature of a causal connection
      with liver damage. We report the case of a 73-year-old woman who developed a
      fatal liver disease of a mixed hepatocellular-cholestatic type after 3 months of
      treatment with dicoumarol. A thorough diagnostic work-up did not reveal any other
      possible cause of the liver disease.

PMID- 9548271
TI  - Theoretical studies on the mobility-shift assay of protein-DNA complexes.
AB  - The theory of mass transport coupled to reversible macromolecular interactions
      under chemical kinetic control forms the basis for computer simulation of the
      electrophoretic mobility-shift behavior of protein-DNA complexes. Model systems
      include (i) specific binding of a univalent protein molecule to a single site on
      the DNA molecule; (ii) the putative cage effect; (iii) cooperative binding to
      multiple sites; (iv) formation of looped complexes of 1:1 and 2:1 stoichiometry;
      (v) noncooperative and cooperative, nonspecific binding modes; and (vi) binding
      of dimerizing transcriptional factors to response elements of target genes.
      Favorable comparison of simulated with experimental mobility-shift behavior
      indicates that the phenomenological mechanisms, whereby observed mobility-shift
      patterns are generated during electrophoresis, are embodied in the theory. These
      studies have provided guidelines for definitive interpretation of mobility-shift
      assays and for the design of experiments to develop a detailed understanding of
      the particular system under investigation.

PMID- 9548272
TI  - Myoglobin intron variation in the Gouldian Finch Erythrura gouldiae assessed by
      temperature gradient gel electrophoresis.
AB  - In this study we show how the use of exon-primed, intron-crossing (EPIC)
      polymerase chain reaction (PCR) of a diploid intronic region, in conjunction with
      temperature gradient gel electrophoresis (TGGE), can be used to detect and
      rapidly assess allelic variation at the nucleotide level. We developed passerine
      specific primers to amplify and sequence a 762 bp region including the second
      intron of the myoglobin gene in the Gouldian Finch, Erythrura gouldiae. A POLAND
      plot based on this sequence indicated that TGGE in combination with heteroduplex
      analysis (TGGE/HA) should reveal nucleotide variation in the 160 bp low-melting
      domain. Sequencing of the entire fragment from 19 Er. gouldiae revealed five
      nucleotide substitution differences within the low-melt domain, all of which
      could be detected and differentiated by TGGE/HA, and an additional substitution
      in a section of the high-melt domain which characterised another allele. A total
      of 181 individuals from four populations were screened for these six alleles.

PMID- 9548273
TI  - Nonradioactive sequence-tagged microsatellite site analyses: a method
      transferable to the tropics.
AB  - Utilization of existing isozyme analysis facilities to detect sequence-tagged
      microsatellite site (STMS) polymorphism or any simple sequence repeat (SSR)
      variation is described. Different parameters concerning the difficulties in
      transferring molecular techniques to less sophisticated laboratory
      infrastructures (i.e. tropical outstations) are discussed (e.g. reproducibility,
      efficacy, precision). Nonradioactive STMS analysis is bound to foster
      collaborative research between "biodiversity" and "biotechnology" centers.

PMID- 9548274
TI  - Oligonucleotide DNA fingerprinting optimized to determine parentage in three
      beetle species.
AB  - Oligonucleotide fingerprinting was performed on three beetle species from
      different families (Coleoptera: Staphylinidae: Aleochara curtula; Silphidae:
      Nicrophorus vespilloides; Tenebrionidae: Blaps lethifera) to obtain detailed
      information on parentage in mating systems. We report variations in the number of
      hybridizing fragments for the different species depending on the combinations of
      probes and restriction enzymes used. In addition to conventional multilocus
      fingerprint patterns, we established a single locus system for A. curtula (GTG5;
      HinfI) and described an oligolocus system in N. vespilloides (GATA4; HaeIII).

PMID- 9548275
TI  - Development of standard reference materials for diagnosis of p53 mutations:
      analysis by slab gel single strand conformation polymorphism.
AB  - We have amplified by polymerase chain reaction (PCR) a 2.0 kbp region of the p53
      gene containing exons 5--9 from seven cell lines reported in the literature to
      contain the majority of mutations reported for this gene. Sequence analysis of
      these products show that all seven cell lines contain mutations within the
      mutational hot spots of the p53 gene. Six of the seven clones have single base
      substitutions and the seventh has a single base deletion. We have analyzed the
      seven p53 single point mutations by single strand conformation polymorphism
      (SSCP) analysis using fluorescence slab gel electrophoresis (SG-SSCP).
      Fluorescent-labeled PCR primers were used for amplification of specific exons for
      mutation detection. SG-SSCP was conducted using Model 373 and Model 377 DNA
      sequencers with GeneScan Software (Perkin Elmer, Applied Biosystem Division).
      Nine different gel systems were first tested for their ability to resolve the p53
      mutations using the Model 373 instrument. Two gel systems were capable of
      resolving all of the mutations that were screened. Optimal results were obtained
      with 12% w/v acrylamide 50:1 plus 10% v/v glycerol. This gel system was used to
      evaluate the effect of temperature on the ability to resolve the mutations. The
      separation with respect to wild type varied for each mutation examined.
      Subambient temperature (20 degrees C) was preferable overall for discrimination
      of these mutations as a group. We intend to use this system to examine a much
      larger panel of p53 mutation standards that are now under development.

PMID- 9548276
TI  - Detection of p53 point mutations by single strand conformation polymorphism:
      analysis by capillary electrophoresis.
AB  - We have analyzed five p53 single point mutations by single strand conformation
      polymorphism using capillary electrophoresis (CE-SSCP) and have compared these
      measurements to measurements obtained by slab gel electrophoresis (SG-SSCP). PCR
      primers were used for amplification of specific exons for mutation detection. 5'
      Primers were labeled with FAM (5-carboxyfluorescein) and 3' primers were labeled
      with JOE (2',7'-dimethoxy-4',5'-dichloro-6-carboxyfluorescein). CE-SSCP was
      performed using the Perkin Elmer ABI PRISM 310 Genetic Analyzer with GeneScan
      Software and the Beckman P/ACE 5510 CE equipped for laser-induced fluorescence
      detection. Although the shifts in migration times for the p53 mutations relative
      to the corresponding wild-type strands could be successfully detected by either
      SG or CE analysis, the individual electrophoresis run times were about tenfold
      faster and more automated with capillary electrophoresis. The CE-SSCP
      measurements were performed at temperatures ranging from 10 to 60 degrees C on a
      prototype instrument. For mutations measured at ambient temperature (25 degrees
      C), characteristic shifts in direction and magnitude were observed in the
      migration times of both strands of all mutations relative to the wild type. This
      demonstrated the ability of CE at ambient temperature to resolve these mutations.
      However, the magnitude and direction of shifts in migration time varied with
      temperature in a discrete pattern for each mutation and resulted in a temperature
      specific profile for each mutation. This demonstrated that extended temperature
      control will be an important advantage in resolving single point mutations by CE
      SSCP. In addition, by using CE, discrete intra-strand isoforms could be easily
      observed at different temperatures. The combination of mutation-specific
      temperature profiling and analysis of isoforms by CE-SSCP should be of help to
      the diagnostic community in the detection of genetic mutations.

PMID- 9548277
TI  - Amperometric pH regulation--a flexible tool for rapid and precise temporal
      control over the pH of an electrolyte solution.
AB  - Temporal control over both pH and ionic strength of an electrolyte solution with
      high accuracy was achieved with a dynamic, computer feedback-controlled
      amperometric pH-stat device consisting of four pH-regulating electrodes placed in
      electrolyte reservoirs that are separated by dialysis membranes from a central
      compartment. Theoretical predictions of the behavior of this arrangement,
      obtained by computer simulation, were validated by running temporal pH programs
      such as step functions, oscillations, and linear pH gradients. Deviations from
      nominal values given by the computer program are within the limits of accuracy of
      the pH-measuring electrodes. No volume changes accompany a change of pH or
      conductivity since ions are forced to leave or enter the central compartment
      through the membranes by the electrical force applied between the pH-regulating
      electrodes. The device is flexible, easy to use and easily miniaturized. We
      discuss a wide range of possible applications in biochemistry and cell science.
      These include automated pH adjustment, isoelectric protein separation,
      amperometric measurement of enzyme kinetics and the response of cell cultures to
      well-defined pH changes.

PMID- 9548278
TI  - Can amphoteric substances with very small (or negative) deltapK difference exist
      and what properties would their water solutions exhibit?
AB  - For calculating the buffer capacity of ampholytes an application of the stepwise
      and parallel dissociation models is considered. It is demonstrated that the
      scheme with stepwise dissociation possesses a "nonadditive" sum, i.e., the
      resulting buffer capacity of the system exceeds the sum of the separate
      contributions of the two ionogenic groups. On the other hand, the scheme of
      parallel dissociation is free from this disadvantage, and thus does not impose
      any restriction on the deltapK parameter.

PMID- 9548279
TI  - Isotachophoresis at pH extremes: theory and experimental validation.
AB  - The evolution of an isotachophoresis (ITP) system in acidic or basic pH ranges
      can be quite different from that predicted by the existing theory. It was found
      theoretically and proved experimentally that the contribution of hydrogen or
      hydroxyl ion to conductivity of solution and/or its net charge changes the
      behavior of the ITP system, creating in the terminating electrolyte an additional
      zone close to the initial interfaces between electrolytes (leader and
      terminator). One boundary of the zone, being either sharp or dispersed, moves
      toward the leader; the other is always sharp and stationary and coincides with
      initial electrolytes' discontinuity. The latter can be registered in the presence
      of electroosmotic flow which delivers it to the detection point. In order to
      describe the dynamics of the ITP system at pH extremes an algorithm of analytical
      solution was developed, based on the revised Kohlrausch theory. Its predictions
      coincide well with computer simulations and experimental data. The results
      presented can help in a correct analysis of ITP data and explain some confusing
      phenomena which were considered to be artifacts.

PMID- 9548280
TI  - Enhanced detection sensitivity of "fluorescence reduction" by shifting the
      analyte absorbance spectrum and use of a fluorescent paper with higher
      signal/noise ratio.
AB  - Nonfluorescing protein bands can be detected by the fluorescence optics of the
      commercial gel electrophoresis apparatus with automated scanning of the migration
      path (HPGE-1000, LabIntelligence, Belmont CA), taking advantage of the decrease
      of emission from a fluorescent paper placed below the gel by the absorbance of
      proteins ("fluorescence reduction"). That decrease of fluorescence gives rise to
      an inverted protein peak. Nonfluorescent colorless proteins appear to reduce the
      intensity of light emitted from the fluorescent paper due to absorbance of
      incident and emitted light. When the absorbance spectrum only slightly overlaps
      with the excitation and emission spectra of the fluorescent paper, that reduction
      is weak, and detection sensitivity in that application is consequently only 1/30
      of that of fluorescent proteins. By contrast, when the protein is colored so that
      its absorbance spectrum overlaps widely with the excitation and emission spectra
      of the fluorescent paper, the sensitivity of "fluorescence reduction" equals 1/4
      to 1/5 of that obtained for fluorescent proteins. Bands detected by "fluorescence
      reduction" provide a quantitative measure of protein load and mobility. The area
      of the inverted bands is proportional to protein loads up to 16 microg/lane of
      the gel tray. A theory of "fluorescence reduction" is presented which accounts
      for the existence of a linear relationship between band area and load.

PMID- 9548281
TI  - Activity staining on polyacrylamide gels of trypsin inhibitors from leaves of
      sweet potato (Ipomoea batatas L. Lam) varieties.
AB  - The failure of activity staining of trypsin inhibitors in crude leaf extracts of
      sweet potato varieties including Tainong 27, Tainong 34, and Tainong 57 on a 15%
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel was
      prevented by dipping the gels in solutions containing 10-40 mM hydrogen peroxide,
      10 mM Tris buffer (pH 7.9) for 30 min before staining.

PMID- 9548282
TI  - Electrophoretic applications of phycobiliproteins.
AB  - Phycobiliproteins are homologous chromoproteins which constitute the
      phycobilisomes, the light harvesting complexes of the photosynthetic apparatus in
      cyanobacteria, rhodophyta and cryptophyta. In the present work, phycocyanin (PC)
      and phycoerythrin (PE) from a Nostoc species are proposed as protein markers for
      electrophoretic techniques. Phycocyanin is a blue-colored phycobiliprotein; it
      carries phycocyanobilin as chromophoric group and is composed of two subunits,
      alpha and beta, with Mr of 14000 and 17000, respectively. In contrast, the PE
      subunits, having a similar Mr of 21000, are deep rose chromoproteins and carry
      phycoerythrobilin residues. Both low molecular weight phycobiliproteins are also
      suitable for monitoring protein blotting and the focusing time of protein samples
      during isoelectric focusing as internal markers. The PE subunits which form a
      single broad band after sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      have different isoelectric points, and they form two visible bands when they
      reach their isoelectric point. The phycobilisomes constitute up to 50% of the
      total protein in cyanobacteria and their content in PC or PE can be up- or down
      regulated by using different light conditions (chromatic adaptation).

PMID- 9548283
TI  - Elution of glycoproteins from replicas of sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis gels.
AB  - A method for the elution of glycoproteins from sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) replicas of gels on polyvinylidene
      difluoride (PVDF) membranes is described. Ten model glycoproteins were resolved
      by SDS-PAGE and then electrotransferred onto PVDF membranes. After reversible
      staining, glycoprotein bands were eluted with a mixture of SDS/Triton X-100 at pH
      9 or with a mixture of guanidinium hydrochloride/lysophosphatidylcholine at
      neutral pH. For both types of eluents, the final recoveries ranged from over 30%
      to about 80%. Good recoveries and mild conditions of elution render the method
      applicable for the structural elucidation of glycan chains.

PMID- 9548284
TI  - Separation of 4-color DNA sequencing extension products in noncovalently coated
      capillaries using low viscosity polymer solutions.
AB  - A low viscosity (ca. 75cP) solution using polydimethylacrylamide (PDMA) was
      developed for separating DNA sequencing extension products by capillary
      electrophoresis (CE). This medium gave a length-of-read (LOR) value of
      approximately 600 bases in about 2 h using four-color sequencing in 50 microm
      capillary at 42 degrees C under a field of 160 V/cm. This medium also works in
      bare capillaries by noncovalently coating the surface to suppress both
      electroosmotic flow (EOF) and DNA-capillary wall interactions, and eliminates the
      need for complicated covalent coatings. At least 100 successive sequencing runs
      were performed in the same capillary by simply pumping fresh medium after every
      run, without requiring any reconditioning of the capillary surface between runs.
      The thermal stability of the noncovalent coating can be improved by adding small
      amounts of high molecular weight PDMA to the separation medium. The advantages of
      low viscosity separation media and uncoated capillaries are of paramount
      importance to develop high-throughput instruments for DNA sequencing.

PMID- 9548285
TI  - Viscosity-adjustable block copolymer for DNA separation by capillary
      electrophoresis.
AB  - The viscosity-adjustable property of F127 block copolymer PEO99PPO69PEO99, PEO
      and PPO being poly(ethylene oxide) and poly(propylene oxide), respectively, was
      found to be useful for the development of automated capillary electrophoresis
      (CE). The polymer solution can form a gel-like structure with sieving ability and
      can also serve as a dynamic coating material, thereby effectively suppressing the
      electroosmotic flow induced by the ionization of the silanol group on the quartz
      capillary inner wall. When applied to CE as a separation medium, F127 block
      copolymer can provide the advantages of high separation resolution, easy
      injection and replacement of the triblock copolymer solution and convenient
      capillary column treatment. High reproducibility of DNA electrophoretic migration
      time in CE by replenishing F127 solution in acid-washed capillary tubings can be
      achieved. The relative standard deviation of the DNA migration time is less than
      2%. In the investigation of F127 concentration and temperature effects on the
      performance of DNA separation in CE, we have found that the DNA electrophoretic
      migration behavior in the F127 gel-like solution cannot be described by any one
      of the existing models.

PMID- 9548286
TI  - Characterization of high molecular mass linear polyacrylamide powder prepared by
      emulsion polymerization as a replaceable polymer matrix for DNA sequencing by
      capillary electrophoresis.
AB  - In a previous paper, a 2% w/w replaceable high molecular mass linear
      polyacrylamide solution (high molecular mass LPA) was used to achieve long read
      lengths for DNA sequencing by capillary electrophoresis (E. Carrilho et al.,
      Anal. Chem. 1996, 68, 3305-3313). In that work, the polymer was prepared by
      polymerization in water at 6% w/w, followed by dilution to 2% w/w. In this study,
      an improved method for preparation of high molecular mass LPA was developed,
      based on inverse emulsion polymerization. With this polymerization procedure, the
      LPA results in a molecular mass of approximately 9 MDa, with characteristics of a
      fine powder of high purity and practically unlimited shelf life. Using size
      exclusion chromatography (SEC) and viscosity measurements to characterize the
      polymer, good batch-to-batch reproducibility was found. It was observed that the
      viscous polymer solutions made from these high molecular mass polymers require
      careful preparation and handling because the method of dissolution could affect
      the molecular mass distribution and the resultant separation of DNA components.
      Solutions containing 2% w/w of LPA made by emulsion polymerization were simple to
      prepare, resulting in excellent performance as a replaceable matrix for DNA
      sequencing by capillary electrophoresis. The viscosity of the polymer decreased
      exponentially when pressure was applied, allowing easy replacement from a
      capillary using a syringe. With a properly prepared matrix, a read-length of more
      than 1000 bases in 80 min with an accuracy better than 97%, and better than 99%
      for the first 800 bases, could be achieved.

PMID- 9548287
TI  - Fast detection of a (CA)18 microsatellite repeat in the IgE receptor gene by
      capillary electrophoresis with laser-induced fluorescence detection.
AB  - The optimum separation conditions of polymerase chain reaction (PCR) products
      have been found for high-speed capillary electrophoresis (CE) with laser-induced
      fluorescence (LIF) detection. DNA fragments obtained after PCR amplification of
      the region covering the (CA)18 microsatellite repeat in nitron 5 of the gene for
      FcERIbeta, a high affinity glycoprotein receptor for IgE, located on chromosome
      11 (11q13), were analyzed with the aim of investigating the repeat polymorphism.
      The results of polyacrylamide slab gel electrophoresis (PAGE), agarose gel
      electrophoresis, CE with absorbance detector and CE with LIF are compared. The CE
      with LIF proved to shorten analysis time by a factor of 100 when compared to slab
      gel electrophoresis. CE-LIF utilizes a short capillary with an effective length
      of 6.3 cm and electric field strength from 100 to 550 V/cm. The respective PCR
      products of sizes from 116 to 210 base pairs (bp) were analyzed in 3 min.

PMID- 9548288
TI  - Forensic validation of the short tandem repeat HUMACTBP2 using capillary
      electrophoresis.
AB  - Experiments were performed to evaluate the forensic identification of the short
      tandem repeat (STR) HUMACTBP2 (human beta-actin-related pseudogene) using
      automated fluorescence-based capillary electrophoresis. The HUMACTBP2 is a
      complex tetranucleotide STR locus with more than 32 alleles in the range of 202
      323 bp. The reproducibility of genetic typing using a fluorescent labeled allelic
      ladder was determined by comparison of the calculated fragment size after
      consecutive (within-day) and nonconsecutive (day to day) injection. The maximum
      variation in size (window) observed for any allele was 0.23 bp for the within-day
      and 0.8 bp for the day-to-day precision. Furthermore, it is possible to achieve a
      1 bp resolution, the precision of the reproducibility assays being about 99.95%.
      Sixty blood samples and twenty stains were typed with both automated fluorescent
      sequencer ABI 373A and ABI 310. Identical genotypes were obtained with both
      techniques and the ABI 310 seemed to be more sensitive than the ABI 373A. A
      population sample of 197 unrelated individuals from southwest Switzerland was
      analyzed and the genotype frequencies observed were similar to those reported by
      others. Thirty-one alleles and 126 genotypes were found. The observed
      heterozygosity was 0.934. Mixtures from two different blood samples varying in
      their ratio were typed and the minor fraction was detectable to about 1:10. The
      practical usefulness of the HUMACTBP2 is illustrated by analyzing casework
      samples. This validation study proves the usefulness of the HUMACTBP2 locus in
      forensics and the detection efficiency using fluorescent capillary
      electrophoresis.

PMID- 9548289
TI  - Capillary electrophoresis of peptides and proteins in fused-silica capillaries
      coated with derivatized polystyrene nanoparticles.
AB  - High-resolution capillary electrophoretic separation of proteins and peptides was
      achieved by coating the inner wall of 75 microm ID fused-silica capillaries with
      40-140 nm polystyrene particles which have been derivatized with alpha-omega
      diamines such as ethylenediamine or 1,10-diaminodecane. A stable and irreversibly
      adsorbed coating was obtained upon deprotonation of the capillary surface with
      aqueous sodium hydroxide and subsequent flushing with a suspension of the
      positively charged particles. At pH 3.1, the detrimental adsorption of proteins
      to the capillary inner wall was suppressed efficiently because of electrostatic
      repulsion of the positively charged proteins from the positively charged coating
      which enabled protein separations with maximum efficiencies of 400000 plates per
      meter. A substantial improvement of separation efficiency in particle-coated
      capillaries was observed after in-column derivatization of amino functionalities
      with 2,3-epoxy-l-propanol, resulting in a more hydrophilic coating. Five basic
      and four acidic proteins could be separated in less than 7 min with efficiencies
      up to 1900000 theoretical plates per meter. Finally, coated capillaries were
      applied to the high-resolution analysis of protein glycoforms and bioactive
      peptides.

PMID- 9548290
TI  - Selenium speciation by interfacing capillary electrophoresis with inductively
      coupled plasma-mass spectrometry.
AB  - The high resolution potential of capillary electrophoresis (CE) makes CE
      techniques valuable for separations of selenium species. Further, inductively
      coupled plasma-mass spectrometry (ICP-MS) affords element-specific multi-element
      detection, providing extremely low detection limits. The combination of CE with
      ICP-MS promises to become a powerful tool for metal speciation. Therefore, an on
      line hyphenation of CE with ICP-MS, which was developed earlier (Michalke, B.,
      Schramel, P., Fresenius' J. Anal. Chem. 1997, 257, 594-599), was modified and
      applied to selenium speciation. For this reason, capillary zone electrophoresis
      (CZE) methods were developed, providing the possibility to analyze six Se species
      of interest in one run: Se (IV), Se (VI), selenium carrying glutathione (GSSeSG),
      selenomethionine (SeM), selenocystine (SeC), and selenocystamine (SeCM). The
      final CE method used an alkaline background electrolyte (Na2CO3/NaOH) with
      separation differentiated from the detection step during hyphenation. This
      resulted in short separation times (10 min) and a subsequent detection step of
      100s. The Se species were sufficiently separated from each other and appeared at
      7s (SeCM), 16s (Se [VI]), 22s [SeC], 27s (Se [IV]), 35s [SeM] and 56s (GSSeSG)
      during the detection step. Detection limits were calculated as 10 or 20 microg
      Se/L for inorganic Se species and 35-50 microg Se/L for organic Se species.

PMID- 9548291
TI  - Methods for determination of electrophoretic mobility and stability of complexes
      originating in solutions during the chiral discrimination process.
AB  - An equation for the calculation of electrophoretic mobility of kinetically labile
      complexes originating in solutions during the chiral discrimination process is
      derived. The mobility of the complex is calculated from that of a fully ionized
      racemic compound, measured in absence of the chiral selector, and from the
      effective mobilities of its enantiomers, corresponding to the concentration of
      the chiral selector causing their maximum difference. Correct values of
      stoichiometric stability constants of both enantiomers may be calculated from the
      mobility of the complex obtained in this way. Both the mobility and the stability
      values hold only for the experimental conditions used and the selected background
      electrolyte. The proposed method is demonstrated for the separation of the fully
      ionized N-t-BOC-DL-tryptophan with beta-cyclodextrin in 20 mM aqueous solution of
      alpha-hydroxyisobutyric acid, adjusted with NaOH to pH 4.5. Mobility of the
      complex is 8.4 X 10(-9) m2V[-1]s(-1) at 25 degrees C. The stability constants of
      D- and L-enantiomers of N-t-BOC-DL-tryptophan with beta-cyclodextrin, KD and KL
      obtained from migration data using this mobility of the complex, are 374+/-37 M(
      1) and 336+/-31 M(-1), respectively. The geometrical mean value of calculated
      stability constants, 355 M(-1), agrees perfectly with the value of 350 M(-1),
      calculated from the same experimental data by another procedure recently.

PMID- 9548292
TI  - Stereoselective interaction of drug enantiomers with human serum transferrin in
      capillary zone electrophoresis (II).
AB  - Further studies on chiral resolution of drugs with different chemical structures
      by capillary zone electrophoresis using iron-free human serum transferrin are
      described. The substances passed a highly concentrated pseudo-stationary protein
      zone applied in a coated capillary and the possible chiral separation of the
      optical isomers was followed. Eighteen drugs with different structures were
      screened, and the enantiomers of clofedanol, buphenine, acebutolol and
      chlorphenamine were resolved. Several, but not all drugs, showed longer migration
      times while passing the protein zone, indicating an interaction with transferrin,
      although chiral resolution was not observed in all cases. The observations
      provided further information about the properties of the surface interaction
      sites of transferrin.

PMID- 9548293
TI  - Separation of cis/trans conformers of human and salmon calcitonin by low
      temperature capillary electrophoresis.
AB  - Conformer-specific recognition of peptides and proteins has often been proved
      with the aid of indirect methods. Here we provide an analytical approach for a
      direct investigation of separated isomers. Cis/trans conformers of the peptide
      hormones human (hCT) and salmon (sCT) calcitonin exhibit different migration
      properties in capillary zone electrophoresis at subambient temperatures.
      Calcitonin consists of 32 amino acids with two proline residues incorporated. It
      is the longest unstructured peptide for which a conformer separation by capillary
      electrophoresis has yet been achieved. Lowering the temperature yielded a
      splitting into two and three peaks for sCT and hCT, respectively, in acidic
      buffer. The peak ratios of 66:34 for sCT and 71:23 for hCT are in good agreement
      with the conformer distribution previously reported from nuclear magnetic
      resonance (NMR) studies. The addition of different organic modifiers (5-20% v/v)
      to the running buffer does not improve the separation. The observed merging of
      conformer peaks in buffer containing 20% v/v 2,2,2-trifluoroethanol (TFE) is
      attributed to structure formation.

PMID- 9548294
TI  - Analysis of polyanionic macromolecular carrier poly-(N-vinylpyrrolidone-co-maleic
      acid) and its bioconjugats by capillary electrophoresis.
AB  - Anionic carrier poly(N-vinylpyrrolidone-co-maleic acid) and its conjugates,
      prepared with coupling of 2-cyano-3-hydroxy-5-amino-2-pentenoyc(4-trifluoromethyl
      anilide) or (6', 7'-dimethyl-l'-quinoxalinyl)-4-(2' amino) acetanilide to the
      carrier, were analyzed by capillary zone electrophoresis (CZE) and micellar
      electrokinetic chromatography (MEKC) in the following buffers: 0.25 N
      triethylammonium phosphate (TEAP); sodium dodecyl sulfate (SDS; 25-150 mM) in
      TEAP (pH 2.25-6.30); 0.1 N Na-borate buffer (pH range 7-11) and SDS (25-150 mM)
      in Na-borate buffer (pH range 7-11). The presence of strong carboxyl groups
      (dissociated even at pH 2.25) on the polymer chain was proved by the CZE method.
      It was also proved by potentiometric titration that carboxyls with a wide range
      of acidity were on the polymer chain. CZE was able to differentiate among the
      analytes possessing carboxyl groups of different acidic strengths at pH 2.25.
      These components were not distinguished by CZE at high pH values (11.0).
      Interaction between the analyte and SDS affected the separation at this pH, and
      hence good resolution was obtained by MEKC. Informative separations were achieved
      both for the carrier and the conjugates in TEAP buffer at pH 2.25 by the CZE
      method. Optimal separation was achieved in borate buffer containing 75 mM SDS at
      pH 11.0 for the carrier and at pH 7.7 for the conjugates in MEKC.

PMID- 9548296
TI  - Quantitative trace analysis of interleukin-3, interleukin-6, and basic model
      proteins using isotachophoresis-capillary zone electrophoresis with hydrodynamic
      counterflow.
AB  - A quantitative analytical technique to determine trace concentrations of
      recombinant human interleukin-3 (rhIL-3), recombinant human IL-6 (rhIL-6), and
      various basic model proteins is described using isotachophoresis-capillary zone
      electrophoresis (ITP-CZE). Proteins were separated on coated fused-silica
      capillaries using a commercial capillary electrophoretic system modified for the
      application of isotachophoretic preconcentration with hydrodynamic counterflow.
      The effect of injection time and isotachophoretic focusing time was investigated
      and compared with predictions from existing mathematical models. Good linearity
      of the calibration graphs (r > 0.995) was observed for all investigated proteins.
      The limit of quantification was in the 10(-8) M range using UV detection at 200
      nm. Within-day and between-day precision of peak area ranged between 1 and 6%.
      Precision was unaffected by isotachophoretic preconcentration. In conclusion, the
      described method is feasible to quantify trace concentrations of rhIL-3, rhIL-6,
      and basic proteins. Potential applications comprise issues of pharmaceutical
      quality control.

PMID- 9548295
TI  - Quantitative trace analysis of L-ascorbic acid in human body fluids by on-line
      combination of capillary isotachophoresis and zone electrophoresis.
AB  - On-line combination of capillary isotachophoresis and zone electrophoresis
      performed in two coupled capillaries (ITP-CZE) is used for the trace analysis of
      L-ascorbic acid in human serum, urine and stomach fluid. At the ITP stage,
      anionic sample components are separated into individual zones and macrocomponents
      are detected and driven out of the migration path. In the CZE stage, only a small
      segment of the sample zones containing L-ascorbic acid is analyzed. High
      sensitivity of this hyphenated method (limit of detection, 0.09-0.15 mg/L), low
      sample volume consumption (2 microL), and acceptable reproducibility of the
      results (relative standard deviation, 8%) in the concentration range 0.1-15 mg/L
      demonstrate that the method is applicable for the study of the relation between
      the content of L-ascorbic acid in body fluids and the state of health of a
      person, in which lower amounts of L-ascorbic acid than the normal levels (i.e.,
      5.1-15.1 mg/L in human serum and 12.5-26.8 mg/L in urine) are expected. Possible
      interferences of other components of the body fluids are excluded by good
      correlation of the results obtained by the ITP-CZE method and a routine
      colorimetric method.

PMID- 9548297
TI  - Wheat cultivar discrimination by capillary electrophoresis of gliadins in
      isoelectric buffers.
AB  - A modified method is reported for screening of wheat cultivars: capillary zone
      electrophoresis of gliadins in isoelectric buffers. Previously published
      procedures recommended a 100 mM phosphate buffer, supplemented with 0.05%
      hydroxypropylmethylcellulose and 20% acetonitrile, in uncoated capillaries. Due
      to the very high conductivity of such a buffer (4.7 mmhos at 25 degrees C) high
      speed separations (10-12 min analysis time at 800 V/cm) could only be elicited in
      20 microm internal diameter (ID) capillaries, at the expense of sensitivity. In
      the present report, we optimized the background electrolyte as follows: 40 mM
      aspartic acid (pH=pI=2.77) in the presence of 7 M urea and 0.5% short-chain
      hydroxyethylcellulose (Mn 27000 Da; apparent pH 3.9 in 7 M urea). As an
      alternative recipe, the same isoelectric buffer can be supplemented with a mixed
      organic solvent composed of 4 M urea and 20% acetonitrile (apparent pH 3.66). Due
      to the much lower conductivity (0.7 mmhos), separations can be carried out at
      1000 V/cm in only 10 min, but in larger bore capillaries (50 microm ID), ensuring
      a five-times higher sensitivity. The gliadin patterns thus obtained are species
      specific and allow easy identification of all cultivars tested of both durum and
      bread wheat. No adsorption of proteins to the silica wall seems to occur and high
      reproducibility in peak areas and transit times is obtained.

PMID- 9548298
TI  - Sodium alkyl ether sulfate preparative electrophoresis for the preparation of
      reaction centers without H-subunit from Rhodopseudomonas viridis.
AB  - Sodium alkyl ether sulfate (AES), an analog of sodium dodecyl sulfate (SDS) was
      used in polyacrylamide gel electrophoresis (PAGE) for the partial decomposition
      of the photosynthetic reaction center (RC) of Rhodopseudomonas viridis. Unlike
      SDS, AES did not completely dissociate RC into its subunits but selectively
      detached H-subunit from RC to give RC(-H) without losing the spectroscopic nature
      of RC. For the denaturation of RC(-H), AES was found to be as mild as 3-[3
      cholamidopropyl)dimethylammonio]-l-propanesulfonate (CHAPS).

PMID- 9548299
TI  - Expression and subcellular distribution of filamin isotypes in endothelial cells
      and pericytes.
AB  - Two principal forms of the actin binding protein, filamin, are expressed in
      mammalian cells: nonmuscle and muscle isotypes (FLN-1 and FLN-2). A protein that
      copurifies with an alpha-naphthyl acetate hydrolyzing esterase from human omentum
      microvessel endothelial cells (EC) is isolated by nondenaturing electrophoresis,
      sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and
      electroblotting. The purified protein is subjected to in situ trypsin cleavage,
      reversed-phase high performance liquid chromatography (HPLC) and automated Edman
      degradation. Six peptide fragments from the protein are identified to have 60-66%
      identity with nonmuscle filamin (ABP-280). Two of these peptides are 100%
      identical to a previously sequenced human muscle filamin fragment. Polyclonal
      antibody is produced using a 16-residue synthetic peptide corresponding to a
      structural beta-sheet region of muscle filamin. Compared with a variety of
      vascular cells evaluated, retinal pericytes express an abundance of both muscle
      and non-muscle filamin isotypes. Pericytes contain at least 10 times more muscle
      filamin than human umbilical vein EC and at least three times the amount
      expressed in human omentum microvessel and bovine pulmonary artery EC.
      Differential detergent fractionation indicates that both filamin isotypes are
      primarily localized in the cytosol and membrane/organelle fractions of pericytes.
      Another actin crosslinking protein, alpha-actinin, is primarily found in the
      cytosol and cytoskeletal fractions. The dynamic regulation of actin microfilament
      organization in pericytes may be controlled in part by the two filamin isotypes,
      which in turn may contribute to pericyte contractility.

PMID- 9548300
TI  - Analysis of differential protein expression in normal and neoplastic human breast
      epithelial cell lines.
AB  - High-resolution two-dimensional gel electrophoresis (2-DE) and database analysis
      was used to establish protein expression patterns for cultured normal human
      mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast
      Epithelial Cell database contains the 2-DE protein patterns, including relative
      protein abundances, for each cell line, plus a composite pattern that contains
      all the common and specifically expressed proteins from all the cell lines.
      Significant differences in protein expression, both qualitative and quantitative,
      were observed not only between normal cells and tumor cells, but also among the
      tumor cell lines. Eight percent (56/727) of the consistently detected proteins
      were found in significantly (P< 0.001) variable levels among the cell lines.
      Eight proteins present in normal cultured breast epithelial cells were not
      detected in any of the tumor cell lines. We identified a subset of the
      differentially expressed proteins using a combination of immunostaining, protein
      sequencing, comigration, and subcellular fractionation. These identified proteins
      include the intermediate filament components vimentin and cytokeratins. The cell
      lines can be classified into four distinct groups based on their intermediate
      filament protein profile. We also identified heat shock proteins; hsp27 and hsp60
      varied in abundance and in some cases in the relative phosphorylation levels
      among the cell lines. Many of the differentially expressed proteins we identified
      have roles in cellular proliferation and differentiation, including annexin V,
      elongation initiation factor 5A, Rho GDP dissociation inhibitor, and prohibitin.
      We identified inosine-5-monophosphate dehydrogenase in each of the cell lines,
      and found the levels of this enzyme in the tumor cell lines elevated 2- to 20
      fold relative to the levels in normal cells. These results expand the human
      breast epithelial cell protein database (http:// www.anl.gov/CMB/PMG) which is
      being built to assist researchers with the identification of abnormal patterns of
      expression and pathways associated with malignancy.

PMID- 9548301
TI  - TMIG-2DPAGE: a new concept of two-dimensional gel protein database for research
      on aging.
AB  - Cellular proteins of a normal human diploid fibroblast line (TIG-3) at various
      stages of replicative aging were resolved by horizontal isoelectric focusing on
      an immobilized pH gradient, followed by vertical sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis (PAGE). Spot proteins were visualized by
      silver staining and quantitated by image processing. All corresponding spots were
      matched among two-dimensional gel images, and variation profiles in relative
      abundance of individual proteins during in vitro aging were classified into five
      categories, i.e., (i) increase, (ii) decrease, (iii) increase followed by
      decrease, (iv) decrease followed by increase, and (v) irregular or nonsignificant
      variation. The new concept of the Tokyo Metropolitan Institute of Gerontology two
      dimensional gel protein database (TMIG-2DPAGE) was prepared from the above data
      to support research on cellular aging. The database was put on our World Wide Web
      home page at the URL of http://www.tmig.or.jp/2D/ to allow free access through
      the Internet. The individual protein data entries were linked to the standard
      spot protein map of the two-dimensional gel image in order to be accessible by
      clicking the mouse on it.

PMID- 9548302
TI  - Plasma protein adsorption patterns on emulsions for parenteral administration:
      establishment of a protocol for two-dimensional polyacrylamide electrophoresis.
AB  - The two-dimensional polyacrylamide electrophoresis (2-D PAGE) of the plasma
      protein adsorption pattern previously established for polymeric nanoparticles was
      modified and transferred to oil in water emulsions for intravenous
      administration. The emulsions were incubated with citrated plasma, and separation
      from excess plasma was performed by centrifugation under optimized conditions:
      15000 g and three washing steps with 0.05 M phosphate buffer, pH 7.4. With this
      sample preparation, coalescence of droplets could be avoided and an unchanged
      surface area maintained, in addition the phosphate buffer minimized artificial
      IgG adsorption. Critical factors affecting sensitivity were contamination of the
      sample by oil residues and the use of thiourea in the immobilized pH gradients.
      Changes in the protein adsorption pattern caused by altered surface properties of
      the emulsion (i.e. adsorbed Poloxamer 407) were detectable when applying the
      optimized protocol. Knowledge of the protein adsorption patterns and their
      correlation to in vivo behavior opens the perspective for the development of
      intravenous emulsions for controlled drug delivery.

PMID- 9548303
TI  - Analysis of changes in acute-phase plasma proteins in an acute inflammatory
      response and in rheumatoid arthritis using two-dimensional gel electrophoresis.
AB  - Two-dimensional (2-D) gel analysis was used to examine differences in the levels
      of 19 plasma proteins: before and after an acute inflammatory reaction
      (parenteral typhoid vaccination) in normal subjects, between rheumatoid arthritis
      (RA) patients and normals and in RA patients treated with tenidap (120 mg) and
      piroxicam (20 mg). Typhoid vaccination increased levels of SAA, haptoglobin
      alpha1, haptoglobin alpha2, haptoglobin beta and alpha1-anti-chymotrypsin but
      decreased transthyretin and apolipoprotein E. In RA patients, serum amyloid A
      (SAA), haptoglobin alpha2, haptoglobin beta, alpha1-antichymotrypsin and C3
      proactivator levels were elevated while apolipoprotein A-I, apolipoprotein A-IV,
      transthyretin, Gc-globulin, alpha2-HS glycoprotein, alpha2-macroglobulin and
      alpha1-B glycoprotein levels were decreased, compared to normals. Compared to
      piroxicam, tenidap lowered levels of alpha1-antiprotease and SAA but raised the
      levels of transthyretin, Gc-globulin, alpha2-HS-glycoprotein and alpha2
      macroglobulin in RA patients. C-reactive protein (CRP) could not be quantified on
      2-D gels but, when measured by rate nephelometry, levels were reduced after
      treatment with tenidap compared to piroxicam. The general pattern of the acute
      phase protein response to an acute inflammatory response to typhoid vaccination
      is similar to that in the chronic inflammatory condition, RA. The impact of
      tenidap on both positive and negative acute-phase proteins in RA patients could
      clearly be distinguished from that of piroxicam.

PMID- 9548305
TI  - Endoscopic manometry of the sphincter of Oddi in patients with Lemmel's syndrome.
AB  - Endoscopic manometry was performed to evaluate the motor activity of the
      sphincter of Oddi (OS) in six patients with Lemmel's syndrome, four of whom had
      acute cholangitis and two of whom had acute pancreatitis. As controls, 24
      patients undergoing cholecystectomy without juxtapapillary duodenal diverticula
      (JPD) for cholelithiasis or cholesterol polyps in the gallbladder were also
      studied. The OS basal pressure and contraction pressure values were 12.4 +/- 5.1
      mmHg and 103.4 +/- 24.3 mmHg, respectively, in the patients with Lemmel's
      syndrome, and 19.5 +/- 5.1 mmHg and 136.8 +/- 28.2 mmHg, respectively, in the
      control patients. These differences between the groups were statistically
      significant; however, the wave frequency was not significantly different between
      the groups. The mean percentages of antegrade, simultaneous, and retrograde
      sequences were 37.5% +/- 11.3%, 19.9% +/- 8.7%, and 43.4% +/- 11.7%,
      respectively, in the patients with Lemmel's syndrome, and 66.5% +/- 11.0%, 20.2%
      +/- 4.7%, and 14.3% +/- 9.2%, respectively, in the controls. The differences
      between the groups were significant (P < 0.01) for the antegrade and retrograde
      sequences. These findings indicate that dysfunction of the OS in patients with
      Lemmel's syndrome could be important in the development of
      hepatocholangiopancreatic disease caused by duodenobiliary and duodenopancreatic
      reflux.

PMID- 9548306
TI  - Serum cell adhesion molecules in patients with colorectal cancer.
AB  - The serum levels of intercellular adhesion molecule-1 (sICAM-1) and endothelial
      leukocyte adhesion molecule-1 (sELAM-1) were determined in 40 patients with
      colorectal cancer. The sICAM-1 and sELAM-1 levels in the drainage venous blood
      adjacent to a tumor were significantly correlated with those in the peripheral
      venous blood in patients without evident hematogenous dissemination of tumor
      cells. The sICAM-1 levels in peripheral venous blood were significantly higher in
      patients with hepatic metastases, while the sELAM-1 levels were significantly
      higher in those with pulmonary metastases. An immunohistochemical study of
      metastatic sites in the liver revealed that ICAM-1 was expressed in cancer
      stroma, but not in the cancer cells. In conclusion, the sICAM-1 and sELAM-1
      levels in the peripheral venous blood in colorectal cancer patients without any
      distant metastasis are likely to reflect the topical production of these cell
      adhesion molecules, and appear to be instructive in predicting hematogenous
      dissemination in patients with colorectal cancer.

PMID- 9548304
TI  - Metabolic alteration in patients with cancer: nutritional implications.
AB  - During the past 20 years, efforts have been made to elucidate the metabolic
      changes observed in patients with cancer by using stable and radioactive isotopic
      tracers. These metabolic changes in patients with cancer may be similar to those
      in other stress conditions, in which glucose production and utilization,
      lipolysis and free fatty acid flux, and net protein catabolism are increased.
      Stress hormones, such as glucagon and catecholamines, and certain cytokines may
      be responsible for these metabolic changes. Although it has been shown that
      cachexia in patients with cancer signals a poor prognosis, efforts to improve the
      clinical outcomes with nutritional support have been disappointing. The failure
      of cancer patients to respond to nutritional support may be related to an
      alteration in the intermediate metabolism. Therefore, further research evaluating
      the metabolic abnormalities associated with cancer may lead to more effective
      nutritional therapies.

PMID- 9548307
TI  - Abdominal surgery for patients on maintenance hemodialysis.
AB  - Despite the growing number of major surgical procedures being performed for
      patients on maintenance hemodialysis, few reports focus on the management and
      outcome of such patients, especially those undergoing major abdominal surgery. We
      conducted a retrospective review of 30 patients on maintenance hemodialysis who
      underwent abdominal surgery, 20 of whom underwent an elective operation and 10,
      an emergency operation. The indications of elective surgery included
      gastrointestinal cancer, biliary tract disease, and abdominal aortic aneurysm,
      while those for emergency surgery mainly involved gastrointestinal perforation or
      bleeding. There were no statistically significant differences between the
      elective group and the emergency group regarding either the mean time on
      hemodialysis or the preoperative clinical data. The morbidity and mortality rates
      were 15% and 10%, respectively, for the patients who underwent elective surgery
      and 50% and 70%, respectively, for those who underwent emergency surgery (P <
      0.01 and P < 0.05, respectively). Those patients with more than a 2-year history
      of hemodialysis had a significantly higher mortality rate following abdominal
      surgery than those with less than a 2-year history (P < 0.01). Thus, the
      morbidity and mortality rates of patients on maintenance hemodialysis who require
      major abdominal surgery are significantly high, which reinforces the need to
      further improve the intensive perioperative management of such patients.

PMID- 9548308
TI  - The suppression of postoperative liver metastasis caused by the continuous
      intraportal infusion of angiogenesis inhibitor FR-118487 in a rabbit colon cancer
      model.
AB  - The inhibitory effect of FR-118487, a potent angiogenesis inhibitor, on
      neovascularization induced by the VX2 tumor was confirmed in a rabbit corneal
      assay. The antimetastatic effect of FR-118487 was also investigated in 21
      rabbits. Spontaneous liver metastases were induced by VX2 tumor cell implantation
      into the ascending colonic wall. FR-118487 was then infused continuously into the
      portal vein for 7 days after resection of the primary lesion at a dose of 1
      mg/kg/day (FR-1 group) or 3 mg/kg/day (FR-3 group). The incidence of liver
      metastases was 71.4%, occurring in 5 of 7 rabbits, in each of the FR-1 and FR-3
      groups, compared with 100%, being all of 7 rabbits, in the control group. The
      number of metastatic foci tended to be less in the FR-1 (31.0 +/- 36.0) and FR-3
      (24.6 +/- 45.1) groups than in the control group (83.7 +/- 73.9) and the weight
      of metastatic foci was significantly less in the FR-1 (1.4 +/- 1.8 g) and FR-3
      (1.3 +/- 2.0 g) groups than in the control group (6.5 +/- 4.9 g) (P < 0.05).
      However, leakage of the colonic anastomosis and body weight loss were limited to
      the FR-3 group. These results suggest that the continuous intraportal infusion of
      FR-118487 at 1 mg/kg/day suppressed liver metastases by inhibiting angiogenesis,
      without producing any adverse effects.

PMID- 9548310
TI  - Changes in lung lobar volume and bronchial deformity after right upper lobectomy.
AB  - To explore the anatomical repositioning of the middle lobe following right upper
      (RU) lobectomy, we measured the lobar volumes of the lung and the branching
      angles of the airway, and defined their changes after RU lobectomy in a rabbit
      model. Groups A1 (n = 10) and A2 (n = 10) were control groups and groups B1 (n =
      10) and B2 (n = 10) underwent RU lobectomy. Casting material was introduced into
      the airway and a heart-lung bloc was removed form the thoracic cavity in all
      groups. In groups A1 and B1, the volume of each lobe of the bilateral lungs was
      measured, while in groups A2 and B2, bronchial casts were made and the branching
      angles of the airway were measured. The volume ratio of the right upper lobe
      (RUL) to the total lung was 12.0 +/- 0.4% in group A1; however, after RU
      lobectomy, the volume ratio of the right middle lobe (RML) to the total lung
      increased from 8.7 +/- 0.6% in group A1 to 13.5 +/- 0.8% in group B1. The volume
      of the left lung also increased from 43.0 +/- 0.5% in group A1 to 48.8 +/- 1.1%
      in group B1. The angle between the truncus intermedius and the RML bronchus was
      significantly smaller in group B2, at 109.0 +/- 3.5 degrees, than in group A2, in
      which it was 138.5 +/- 1.7 degrees. The angle between the RML bronchus and the
      coronal plane was 57.5 +/- 2.5 degrees in group A2 and 33.5 +/- 3.3 degrees in
      group B2. Our method of measuring the bronchial branching angle subsequent to RU
      lobectomy proved useful to illustrate postoperative positional changes and
      expansion of the remaining lobes.

PMID- 9548309
TI  - The adverse effects of octreotide on the healing of colonic anastomoses in rats.
AB  - Octreotide, a long-acting somatostatin analogue, is widely used in
      gastrointestinal hypersecretory states and also for endocrine tumors in an
      attempt to inhibit the paracrine hormones. Although it is well known that
      octreotide inhibits trophic and anabolic hormones, no research has been conducted
      on its adverse effects on wound healing. In the present study, groups of rats
      were given 20 mcg/kg/day octreotide and 100 mg/kg/day hydrocortisone, the latter
      being the negative control group, starting 5 days preoperatively. The colonic
      anastomoses were assessed for healing on postoperative days (PODs) 5 and 8 by
      determining the bursting pressure of the anastomoses, performing
      histopathological analysis, and measuring the hydroxyproline content of the
      anastomotic tissues. Octreotide was found to affect anastomotic healing
      negatively on both PODs 5 and 8, but the negative effect of hydrocortisone was
      significant only on POD 8. No significant difference was found between the
      adverse effects of the two agents on POD 8. These findings indicated that
      octreotide has an adverse effect on the healing of colonic anastomoses in rats.

PMID- 9548311
TI  - Constant infusion rates of lipid emulsions to stabilize plasma triglyceride
      concentrations: medium-chain triglyceride/long-chain triglyceride emulsions
      (MCT/LCT) versus LCT.
AB  - As medium-chain triglyceride emulsions (MCT) are more rapidly hydrolyzed than
      long-chain triglyceride emulsions (LCT), MCT/LCT tends to be infused faster than
      LCT. The purpose of the present study was to determine the most appropriate
      infusion rate for MCT/LCT to stabilize plasma concentrations of triglyceride
      (TG), being equivalent to the optimal infusion rate of the emulsion. A TG clamp
      was set up by raising the mean +/- SD concentrations of TG in plasma, being 1.08
      +/- 0.18 delta mmol l(-1) for LCT, and 1.65 +/- 0.31 delta mmol l(-1) for MCT/LCT
      after a 50-min priming infusion of each emulsion. Thereafter, the infusion rate
      of lipid was controlled every 10 min to maintain a steady concentration of TG for
      a period of 150 min. A constant infusion of glucose at 0.32 g/kg body weight (BW)
      per h was administered for the test period. The weight-based rate of the infusion
      to maintain a steady state of plasma TG concentrations did not differ between
      MCT/LCT and LCT, being 0.125 +/- 0.013 vs 0.117 +/- 0.021 g/kg BW per h, while
      the molar-based infusion rate was 0.203 +/- 0.021 mmol/kg BW per h for MCT/LCT
      and 0.132 +/- 0.023 mmol/kg BW per h for LCT (P < 0.05). These results suggest
      that although 54% more molar MCT/LCT-TG can be hydrolyzed during a constant
      infusion, MCT/LCT should not be infused at a rate faster than 0.1 g/kg BW per h
      under a steady state.

PMID- 9548312
TI  - Massive intraperitoneal hemorrhage caused by a giant exogastric leiomyoblastoma.
AB  - Leiomyoblastomas account for a small percentage of smooth muscle tumors of the
      stomach. Intraperitoneal bleeding is an unusual and unexpected presenting sign.
      We herein present a 43-year-old woman who was urgently operated on due to signs
      of collapse. A large hemorrhagic mass measuring 25 x 18 x 15 cm was found arising
      from the greater curvature of the stomach. A histologic examination demonstrated
      rounded and spindle cells, and rare mitoses were also seen. Although the number
      of mitoses was small, the lesion was nevertheless felt to be consistent with
      malignant leiomyoblastoma because of its large size. Three years later the
      patient is doing well with no evidence of tumor recurrence. We conclude that
      intraperitoneal bleeding due to leiomyoblastoma of the gastrointestinal tract is
      an extremely rare phenomenon and has been described only in a few reports, and
      only one other previous case presented with signs of collapse.

PMID- 9548313
TI  - Malignant fibrous histiocytoma of the stomach: report of two cases.
AB  - Malignant fibrous histiocytoma (MFH) in the stomach is very rare, and only four
      cases have been reported. As a result, there is still little understanding of its
      clinical and pathological features. We recently experienced two cases of gastric
      MFH. The first case was a 78-year-old man with epigastralgia and a loss of body
      weight. Endoscopy revealed an ulcerated submucosal tumor. A gastrectomy was
      performed and the diagnosis of MFH was made histopathologically. The second case
      was a 77-year-old man with pulmonary symptoms. An image diagnosis indicated a
      strong suspicion of lung cancer, and a right middle and lower lobectomy was thus
      performed. One month after the operation, a bleeding gastric tumor was found and
      therefore a gastrectomy was performed. Both tumors were diagnosed as MFH. From
      the analysis of six reported cases including ours, a preoperative correct
      diagnosis is found to be difficult although the lesion has grown to a
      considerable size at the time of operation. Since a metastatic lung lesion was
      first detected in two out of six cases, it is thus recommended that the stomach
      should be examined when lung MFH is found. Considering the high mortality and the
      short survival in the six cases, the prognosis for gastric MFH seems to be poorer
      than that in the extremities. However, lymph node metastasis is uncommon, and a
      curative resection is possible in some cases such as in our second case.

PMID- 9548315
TI  - Amebic liver abscess with jaundice.
AB  - A case of an amebic liver abscess with unusual clinical manifestations is
      presented. A middle-aged male with an abscess in both lobes of the liver
      presented with obstructive jaundice due to pressure on the porta hepatis with
      stasis of the bile in the intrahepatic biliary radicals. The patient did not
      respond to repeated needle aspirations and thus required open drainage.
      Subsequently, the patient developed a biliary leak through the drainage sites,
      and an injection of contrast dye into the cavity revealed a communication between
      the abscess cavities and the biliary tree. The biliary leak stopped
      spontaneously, and the large cavities also closed completely during the followup
      period.

PMID- 9548314
TI  - Colonoscopic diagnosis of lymphoid hyperplasia causing recurrent intussusception:
      report of a case.
AB  - This paper describes a 6-year-old boy with recurrent ileocecal intussusception
      due to lymphoid hyperplasia in the terminal ileum, which was diagnosed
      preoperatively by colonoscopy. At the age of 3 years, he developed diarrhea and a
      tender abdominal mass. He was diagnosed as having intussusception by ultrasound
      and was treated by hydrostatic barium enema. After resolution, he had three
      recurrent episodes of intussusception. A contrast barium enema revealed a small
      mass in the ileocecal region. Colonoscopy showed several exaggerated folds of the
      terminal ileum and a biopsy showed lymphoid hyperplasia. Because the repeated
      intussusception seemed to have been caused by the lymphoid hyperplasia in the
      terminal ileum, he underwent an ileocecal resection without any subsequent
      recurrence. Based on the above findings, we conclude that a colonoscopy may thus
      be useful both for diagnosing lymphoid hyperplasia in the terminal ileum as a
      cause of recurrent intussusception and for deciding how to manage it.

PMID- 9548316
TI  - Laparoscopic cholecystectomy in patients undergoing anticoagulant therapy.
AB  - We recently performed a laparoscopic cholecystectomy on three patients receiving
      preoperative oral anticoagulant therapy. The patients requiring anticoagulants
      for pre-existing cardiac conditions have the following risks at surgery:
      thromboembolism, hemorrhage, endocarditis, and cardiopulmonary dysfunction. In
      patients receiving anticoagulant therapy, one must thus maintain a balanced
      international normalized ratio of the prothrombin time to prevent thromboembolism
      or hemorrhage. Warfarin sodium was discontinued preoperatively in all patients.
      Heparin sodium was individualized according to each patient's risk of
      thromboembolism. As a result, these patients all underwent a laparoscopic
      cholecystectomy without complications. Attention was paid to achieve hemostasis
      in the operative field and the trocar inserted sites during the procedure. The
      administration of warfarin sodium was resumed on the first postoperative day in
      all patients. Restarting warfarin sodium early also helps to simplify
      postoperative management. A broad spectrum of antibiotic therapy was also used to
      reduce the risk of endocarditis. Each patient's cardiopulmonary function was
      carefully monitored. The minimal invasion experienced during a laparoscopic
      cholecystectomy may thus facilitate the management of gallstones in patients
      receiving systemic anticoagulation treatment based on the findings of this
      limited series.

PMID- 9548317
TI  - Anomalous duplicated cystic duct as a surgical hazard: report of a case.
AB  - Anomalies of the biliary ductal system are not uncommon, and their clinical
      significance is variable. We present herein the case of a 70-year-old Japanese
      woman found to have an anomalous duplicated cystic duct, which is an extremely
      rare congenital anomaly. Intraoperative delineation of the anomaly by real-time
      cholangiograms assisted us in being able to subsequently perform a safe
      cholecystectomy. This case serves to demonstrate the importance of being aware of
      the possibility of potential biliary variations in order to avoid ductal injuries
      during biliary surgery.

PMID- 9548318
TI  - Urgent total arch graft replacement in an elderly patient with acute type A
      dissection: report of a case.
AB  - There are many controversies regarding the treatment of acute aortic dissections.
      We herein present the case of an elderly patient over 80 years of age who
      underwent an urgent total arch graft replacement for a Stanford type A acute
      thrombosed aortic dissection complicating cardiac tamponade. An 81-year-old woman
      with chest discomfort and shock that developed 1 day earlier was transferred to
      our hospital by ambulance. A plain chest computed tomogram, aortogram, and an
      echocardiography revealed mild pericardial effusion and an ascending aortic
      aneurysm measuring 5 cm in diameter, but no evidence of an intimal tear in the
      ascending aorta and aortic arch. At operation, after the bloody pericardial
      effusion had been decompressed, her blood pressure was elevated and a type A
      acute thrombosed aortic dissection with the intimal tear in the aortic arch was
      confirmed, with a false channel filled with clotted blood. She underwent a
      successful emergency total arch graft replacement using selective cerebral
      perfusion and open distal anastomosis. The postoperative course was uneventful
      and the false lumen was closed. We thus conclude that early graft replacement
      should be performed on patients with Stanford type A acute thrombosed aortic
      dissection complicating cardiac tamponade, even in elderly patients over 80 years
      old.

PMID- 9548319
TI  - Aortocoronary saphenous vein graft aneurysm in redo coronary artery bypass
      grafting: report of a case.
AB  - We report herein the case of an 80-year-old woman who underwent successful redo
      coronary artery bypass grafting (CABG) for a saphenous vein graft aneurysm found
      10 years after her initial operation. On presentation, coronary angiography (CAG)
      revealed aneurysmal dilatation of the saphenous vein graft and severe stenosis of
      the left main trunk (LMT). A percutaneous transluminal coronary angioplasty
      (PTCA) of the LMT lesion was performed; however, a CAG after the PTCA revealed
      restenosis and the patient developed anginal chest pain at rest. Thus, repeat
      CABG was urgently carried out, which was followed by a good outcome. Histological
      examination of the aneurysmal dilatation showed a true aneurysm. Only 15 other
      cases of redo CABG for this indication have been reported, the features of which
      are also discussed.

PMID- 9548320
TI  - Infected atherosclerotic ulcer of the abdominal aorta as a cause of mycotic
      aneurysm treated by in-situ prosthetic graft reconstruction: report of a case.
AB  - A 68-year-old man with an infrarenal mycotic aneurysm underwent successful in
      situ graft reconstruction using a woven Dacron graft. A tissue culture taken from
      the excised aortic wall revealed Staphylococcus epidermidis, and histological
      study subsequently showed penetrating atherosclerotic ulcers (PAU) involving all
      layers of the aortic wall and marked neutrophilic infiltration with abscess
      formation inside the ulcer. Atherosclerotic aortic lesions such as PAU are
      considered susceptible to bacterial infection, which may lead to the formation of
      an aneurysm after destruction of the vessel wall. Hence, elderly hypertensive
      patients, being at high risk for such aortic pathology, require careful studies
      performed to assess the aorta. The usefulness of computed tomographic (CT) scans
      to determine the presence of PAU or surrounding inflammation should be borne in
      mind even when a small mycotic aneurysm exists.

PMID- 9548321
TI  - Y-shaped tracheobronchial stent for carinal and distal tracheal stenosis.
AB  - A Y-shaped tracheo-bronchial tube was designed and used for two patients with
      carinal stenosis following a lower tracheal resection in one case and a malignant
      tracheal fistula in the other. The tube consisted of three parts including a Y
      shaped, thin-walled, soft silicone stent; a spiral-wire-reinforced main tube; and
      a curved tracheostomy tube. The stent was inserted easily and comfortably through
      the tracheostomy under fiberoptic bronchoscopic guidance with minimal local
      anesthesia. The positioning stability of the tube was excellent because of the
      carina-shaped structure of the tube end. Resistance to compression was
      satisfactory due to the embedded spiral wire. The insertion procedure through the
      tracheostomy was smooth, even in patients whose respiratory condition was severe
      or critical. Satisfactory phonational activity was also provided by breathing
      through the hole on the tube back up to the vocal cord. Bronchoscopic inspection
      was uncomplicated, and the patients themselves could easily clean the stent.
      Since palliation of the airway obstruction is the main purpose of such a stent
      for patients with either severe lower tracheal or carinal stenosis, and because
      of the difficulty of ordinary stent insertion in this part of the airway, this
      device appears to offer excellent stability and easy insertion of the stent. In
      addition, the ease of maintenance and suctioning through the tracheostomal end
      allows for an excellent quality of life in which the patients are able to return
      to their homes.

PMID- 9548322
TI  - Successful resection of a glomus tumor arising from the lower trachea: report of
      a case.
AB  - Tracheal glomus tumors are extremely rare. We present herein the case of a 43
      year-old man with hoarseness who was found to have a glomus tumor arising from
      the lower trachea. Bronchoscopy and chest computed tomography revealed a polypoid
      mass in the membranous portion of the trachea just above the carina. The patient
      underwent successful tracheal sleeve resection and reconstruction. A pathologic
      diagnosis of a glomus tumor with clear surgical margins was subsequently
      confirmed, and the patient is well 20 months postoperatively with an intact
      anastomosis.

PMID- 9548323
TI  - Idiopathic mediastinal fibrosis: report of a case.
AB  - We report herein the case of a 28-year-old woman who presented with a mediastinal
      mass, subsequently confirmed to be idiopathic mediastinal fibrosis. Preoperative
      chest computed tomography (CT) showed a noncalcified mediastinal mass and surgery
      was performed to exclude malignancy. The mass was hard and dense, involved the
      left phrenic nerve, vagus nerve, and left upper lobe, and surrounded the
      subclavian artery, subclavian vein, superior vena cava, and left pulmonary
      artery. Pathologic examination showed the findings of mediastinal fibrosis and
      the mass was partially excised. Postoperative medical treatment was performed
      with prednisolone and tranilast, and a 3-year follow-up has not demonstrated any
      complications.

PMID- 9548324
TI  - Retroperitoneal and scrotal giant liposarcoma: report of a case.
AB  - The case of a 63 year-old man with a giant scrotal and retroperitoneal tumor is
      herein reported. The initial symptoms began in the scrotum and subsequent
      abdominal distention resulted in discomfort 2 years later. The intraabdominal
      organs were under pressure because of the bulky mass, and the patient had
      dyspnea. Ultrasonograpy, computed tomography, and fine needle aspiration biopsy
      investigations all revealed a retroperitoneal tumor suspected to be liposarcoma.
      At operation, a tumor weighing 42 kg was excised. Respiratory support was
      provided in the early postoperative period. The histopathological diagnosis was
      myxoid liposarcoma. The patient was discharged from the hospital 14 days after
      the operation and was scheduled to undergo radiotherapy.

PMID- 9548325
TI  - Laparoscopic resection of a primary retroperitoneal mucinous cystadenoma: report
      of a case.
AB  - Primary retroperitoneal mucinous cystic tumors are extremely rare, and although
      their histogenesis is still uncertain, several theories have been proposed.
      Traditionally, transabdominal laparotomy and enucleation of the cyst is the
      treatment of choice and laparoscopic resection has not previously been reported.
      This paper presents the case of a 48-year-old woman in whom a primary
      retroperitoneal cystic mass, 15 x 13 x 9 cm in size, was successfully resected
      through the laparoscope. Pathological examination revealed a mucinous cystadenoma
      with borderline malignancy. The patient had a prompt recovery and there was no
      evidence of recurrence at her 8-month follow-up. However, the prevention of
      cystic fluid spillage during laparoscopic manipulation is important, especially
      when the pathology of the retroperitoneal cyst is unclear.

PMID- 9548326
TI  - Vertical stab wound to the lumbo-sacral spinal canal: report of a case.
AB  - A 63-year-old man was stabbed by an iron bar in the perineum. On admission, the
      external aspect of this wound appeared to be only a tiny hole. However, the bar
      had penetrated the rectum, sacrum, and lumbar spinal canal up to the third lumbar
      vertebral body. This patient was eventually treated with sacral wound drainage, a
      closure of the rectal wound, and pelvic drainage. Lumbar surgery was not
      performed because computed tomography (CT) and magnetic resonance imaging (MRI)
      did not show a progression of inflammatory changes in either the lumbar canal or
      perispinal hollow caused by the iron bar during the hospital stay. The clinical,
      CT, and MRI findings thus provided important information in the diagnosis and
      treatment of stab wounds.

PMID- 9548327
TI  - Neuroblastoma in an adult with a high serum level of carbohydrate antigen, CA125:
      report of a case.
AB  - We report herein the case of a 56-year-old woman with a neuroblastoma associated
      with a high serum level of carbohydrate antigen, CA125. The patient presented
      with massive ascites and a firm mass in her upper abdomen for which a laparotomy
      was performed. However, a recurrent tumor was found 6 months later and she died
      of the disease within 1 year of surgery despite several courses of adjuvant
      chemotherapy. Neuroblastoma rarely occurs in adults, and the features of 58 adult
      cases described in the world literature is summarized following the presentation
      of the clinical data on this case. The distribution of primary sites in adults is
      dispersed compared to that seen in pediatric cases, while the natural history of
      the disease in adults may be longer and less sensitive to chemotherapy than in
      children. The survival rate of adults with this disease is poor. We conclude that
      aggressive surgical intervention combined with appropriate chemotherapy protocols
      as applied in children should be performed in an attempt to achieve complete
      remission and improve the survival rate of adults with neuroblastoma.

PMID- 9548328
TI  - The development of extrahepatic portal obstruction after undergoing multiple
      operations for a congenital dilatation of the bile duct: report of a case.
AB  - As a long-term complication after undergoing a cystenterostomy for a congenital
      dilatation of the bile duct, liver cirrhosis due to stenosis of the anastomosis
      or reflux cholangitis has been reported in conjunction with subsequent portal
      hypertension. We treated a 48-year-old Japanese woman who developed both portal
      hypertension and pancytopenia after undergoing multiple operations for a
      congenital dilatation of the bile duct. She underwent a Hassab's operation in
      July 1994, when an occlusion of the extrahepatic portal vein, which resulted in
      portal hypertension, was first noted; the liver was microscopically normal. The
      etiology of the extrahepatic portal obstruction in our patient was most likely
      due to either repeated inflammation or adhesion at the hepatic hilus. Based on
      these findings, the differential diagnosis of portal hypertension after an
      operation for a congenital dilatation of the bile duct should therefore include
      an extrahepatic portal obstruction in addition to liver cirrhosis.

PMID- 9548329
TI  - Leiomyosarcoma of the inferior vena cava. Resection and reconstruction of the
      renal vein using the gonadal vein.
AB  - We succeeded in surgically resecting a leiomyosarcoma of the inferior vena cava
      (IVC), which originated at the confluent portion of the right renal vein (RRV),
      together with the IVC and RRV, and also were able to preserve the right kidney by
      reconstructing the RRV with end-to-end anastomosis using the right gonadal vein.
      A good blood flow of the reconstructed RRV was thereafter confirmed by color
      Doppler ultrasonography, and the renal function was also satisfactory. This new
      procedure, a reconstruction of the RRV using the gonadal vein, has not been
      previously reported, but is considered to be an easy and effective method which
      enables the surgeon to preserve the normal right kidney.

PMID- 9548330
TI  - Spinal cord astrocytomas: long-term results comparing treatments in children.

PMID- 9548331
TI  - Modern treatment strategies in medulloblastoma.
AB  - Chemotherapy has an important role in the modern treatment of children with
      medulloblastoma (MB). In patients at high risk, intense chemotherapy should
      improve the survival rate. In low-risk patients chemotherapy should allow the
      dose of craniospinal irradiation to be reduced, which in turn should improve the
      quality of life. In infants under 3 years of age radiotherapy should be delayed,
      or even replaced by postoperative chemotherapy. Chemotherapy is also necessary to
      prevent or treat systemic dissemination. The optimal timing of chemotherapy is a
      focus of contemporary research.

PMID- 9548332
TI  - Chemotherapy in low-grade astrocytoma management.
AB  - The role of chemotherapy (CHT) in the management of low-grade astrocytoma (LGA)
      is still unclear. Nineteen children with nonresectable symptomatic LGA were
      treated with carboplatin (CBDCA) and etoposide (E). There were 15 newly diagnosed
      cases and 4 were relapses; 6 of the children were under 5 years old. In all
      children radiological evaluation by CT scan and/or MRI was performed after four
      courses of CHT. We observed complete response (CR)+ minor response (MR) in 37% of
      these cases and an improvement in neurological symptoms in 63%. Radiological
      evaluation performed in 6 patients who received CHT for longer periods (8-12
      courses) showed major responses (CR+PR) in 67%. Local radiotherapy (40 Gy) was
      administered after CHT in 14 cases, but in 3 of these radiotherapy was delayed
      for 2 years. Five patients did not receive radiotherapy. The overall survival was
      58% after an average follow-up of 60 months. All patients with brain stem tumors
      died of progressive disease even though 3 of these had shown clinical improvement
      after chemotherapy. In conclusion, in the treatment of nonresectable symptomatic
      LGA, CHT with CBDCA associated with E can be used to postpone radiotherapy in
      young children and even to avoid radiotherapy in some cases.

PMID- 9548333
TI  - Abdominal metastases of pediatric brain tumors via ventriculo-peritoneal shunts.
AB  - Internal drainage of cerebrospinal fluid (CSF) to the abdominal cavity via a
      ventriculo-peritoneal shunt (VPS) is a procedure that is commonly used for the
      treatment of obstructive hydrocephalus. As this condition is often caused by
      brain tumors blocking the natural CSF pathways, a VPS, as an artificial
      anastomosis, can provide the means for tumor cells to be spread with the CSF. A
      review of the literature reveals 35 VPS-related abdominal metastases from
      pediatric brain tumors; 17 in patients aged 0-9 (group A) and 18 in patients aged
      10-18 years (group B); the mean age of male patients was 10.5, and that of female
      patients, 7 years. The male-to-female ratio was 1.9 (group A 1.1, group B 3.5),
      and the mean interval between shunt operation and diagnosis of metastases, 16.7
      months (group A 11.6, group B 22.6 months; boys 21.6, girls 7.5 months). During
      the observation period, 22/30=73.3% of the patients died (group A 13/15=86.7%,
      group B 9/15=60%; boys 13/21=61.9%, girls 9/9=100%); their mean survival time
      after shunting was 18.7 months (group A 15.7, group B 23.1 months; boys 25.5,
      girls 9 months). The four most common sources of metastases were germinomas (9
      cases=25.7%; group A none, group B 9), medulloblastomas (8 cases=22.9%, group A
      7, group B 1), endodermal sinus tumors (5 cases=14.3%, group A 1, group B 4), and
      astrocytomas (4 cases=11.4%, group A 4, group B none). Metastases via VPS are
      rare, but should be considered as a possible complication and mode of systemic
      spread in children with primary intracranial malignancy. They have a more
      favorable prognosis in boys and in the second decade of life.

PMID- 9548334
TI  - Intractable seizure disorder associated with chronic herpes infection. HSV1
      detection in tissue by the polymerase chain reaction.
AB  - We describe the pathological findings and report the detection of herpes simplex
      virus 1 (HSV1) in the brain in three patients who presented with intractable
      seizures. All three patients had a previous history of HSV1 encephalitis and went
      on to develop a medically refractory seizure disorder necessitating surgical
      intervention. HSV1 encephalitis was clinically diagnosed and treated at 6 months,
      3 years, and 7 months and surgical resection was done at 8.5 years, 6 years, and
      3 years, in cases 1, 2 and 3, respectively. Pathological examination revealed
      chronic encephalitis in all three cases, with microglial nodules,
      intraparenchymal, perivascular and meningeal lymphocytic infiltrates, and
      gliosis. While immunohistochemical and ultrastructural studies were negative for
      viral pathogens, polymerase chain reaction (PCR) analysis revealed HSV1 genome.
      These cases represent examples of chronic herpes encephalitis and seizure
      disorder with presence of viral genome in the brain long after the initial
      episode of treated herpes encephalitis.

PMID- 9548336
TI  - The Surgical Isolation Bubble System and patient temperature during
      ventriculoperitoneal shunt insertion in preterm and term newborn infants.
AB  - The ultraclean air environment in a plastic isolator has been used in
      cerebrospinal fluid shunt interventions in an attempt to reduce the incidence of
      infections. The blower that maintains a continuous flow of filtered air in the
      operative field may create body temperature changes. In this study we assessed
      the temperature before, during and at the end of the operation in preterm and
      term infants in whom ventriculoperitoneal shunts were being placed. There were 12
      preterm and 9 term infants. The duration of the operative intervention ranged
      from 25 to 50 min. In the preterm infants the mean initial temperature was 36.2+/
      0.2 degrees C, and the final temperature was 35.7+/-0.2 degrees C. This
      difference was not significant. The initial temperature in the term infants was
      36.26+/-0.2 degrees C, and the final temperature was 35.9+/-0.3 degrees C, also
      not significantly different. The surgical isolation bubble system does not alter
      the temperature of preterm and term infants significantly during
      ventriculoperitoneal shunt procedures performed within the operative times seen
      in this study.

PMID- 9548335
TI  - Ornithine decarboxylase in developing brain of hydrocephalic rats. Effects of
      shunt operation.
AB  - We examined the changes in ornithine decarboxylase (ODC) immunoreactivity in the
      hydrocephalic cerebral cortex of HTX rats after decompression by shunt operation.
      The ODC immunoreactivity reached a very low level after the completion of
      cortical layer formation, and only faint staining was found on postnatal day (Pd)
      11. The ODC immunoreactivity re-appeared after the shunt operation when the
      operation was done in the early days of life: the ODC immunoreactivity was first
      found on day 2 after shunting and persisted until day 8 after shunting. However,
      this was not apparent when the operation was not performed until Pd 14. The re
      expression of ODC in hydrocephalic brain after shunting appears to cause
      resumption of the developmental process by relieving neurons from increased
      hydrostatic pressure. The dependence of ODC re-expression on the timing of the
      operation indicates that there may be a period of neocortical decompression that
      is critical for effective compensatory development, so that when delayed,
      decompression fails to re-activate the ODC-dependent development.

PMID- 9548337
TI  - Patient satisfaction with surgical treatment of refractory epilepsy done in
      childhood and early adolescence.
AB  - The results of a retrospective self-controlled telephone satisfaction survey of
      63 patients who had undergone an earlier resection for the treatment of medically
      refractory epilepsy before the age of 18 years was reported. The survey items
      consisted of a global rating scale and a series of open-ended questions about
      positive and negative outcomes as a result of the surgery. Most (80%) of the
      patients felt the surgery had had a positive effect on their lives. The mean
      global score was 6.24+2.4 (scale 0-9). Strong positive correlations were found
      between seizure control and degree of satisfaction and between perceived
      postsurgical neurological deficits and dissatisfaction.

PMID- 9548338
TI  - Recent advances and racial differences in therapeutic strategy to the pineal
      region tumor.
AB  - The therapeutic modalities for pineal region tumors in Western countries differ
      from those in Japan, mainly because of the different patient populations. The
      majority of pineal region tumors in Japan are radio- and/or chemosensitive, and
      adjuvant therapy rather than extensive surgery plays the main part in the
      treatment of these tumors. The specific clinical features of and therapeutic
      modalities for pineal region tumors, together with racial differences, were
      analyzed at the joint symposium of the Japanese Society for Pediatric
      Neurosurgery and the Korean Society for Pediatric Neurosurgery. The results of a
      cooperative study, together with the collective experience in Korea, confirmed
      that this specific patient population is nearly identical to the Japanese one.
      The new therapeutic approaches to pineal region tumors recommended included
      neuroendoscopic or stereotactic biopsy as a "minimally invasive" initial
      procedure. The adjuvant therapeutic modalities were further analyzed and
      neoadjuvant chemotherapy, mainly with cisplatin or carboplatin with or without
      etoposide (VP-16), was recommended for the treatment of germinoma and
      nongerminomatous malignant germ cell tumors. "Target radiation therapy" with
      extensive chemotherapy is a hopeful regimen and a future subject of research.

PMID- 9548340
TI  - Treatment of germ cell tumors in the pineal region.
AB  - The authors retrospectively analyzed 107 patients with primary intracranial germ
      cell tumor (GCT), who were treated at the Department of Neurosurgery, Yonsei
      Medical Center between January 1986 and January 1996. The incidence of GCT was
      2.8% in pediatric patients with intracranial tumor. Of the 107 tumors, 60 were
      located in the pineal region, 30 in the suprasellar region, 16 in basal ganglia
      or the thalamic region, and 1 in the posterior fossa. The 60 pineal GCT consisted
      of 39 germinomas (29 pure germinomas, 6 germinomas with STGC, 4 germinomas mixed
      with teratoma), 5 mature teratomas, and 16 nongerminomatous GCT. Thirty patients
      underwent surgery: their operations took the form of total resection in 14 cases,
      subtotal resection in 10, and biopsy in 6. Thirty patients (27 with germinomas, 3
      with endodermal sinus tumors) were managed without surgery on the basis of
      radiological findings and tumor markers. The 5-year survival was 91% for 39
      patients with germinomas, 80% for 5 with mature teratomas, and 49% for 16 with
      nongerminomatous GCT. Univariate analysis of prognostic factors with the Kaplan
      Meier survival curve showed that histological tumor type, radiological findings,
      results of tumor marker studies, and response to trial radiation or chemotherapy
      were highly correlated with outcome. Chemotherapy was beneficial as the method of
      trial treatment in pineal GCT and treatment in recurrent tumors. The
      administration of trial chemotherapy or radiotherapy without tissue biopsy is
      well justified as a treatment modality in pineal GCT suspected on the basis of
      radiological findings and tumor marker studies. Aggressive multimodality
      approaches with surgery, radiotherapy, and chemotherapy are necessary to improve
      the outcome in these tumors. We propose new protocol for treatment of germ cell
      tumors in the pineal region, which is based on a minimally invasive approach.

PMID- 9548339
TI  - Identical characteristics of the patient populations with pineal region tumors in
      Japan and in Korea and therapeutic modalities.
AB  - The therapeutic modalities used for tumors of the pineal region in Western
      countries differ from those in Japan, mainly because of the different patient
      populations. An extensive survey was conducted to delineate the racial
      differences in Japan and in Korea in the epidemiology and recent therapeutic
      modalities for this tumor group. Among the members of International Society for
      Pediatric Neurosurgery (ISPN), 15 from Japan and 5 from Korea reported their
      recent findings in 118 (1-25 years of age, mean 7.38-year period) and 125 (1-12
      years of age, mean 6.69-year period) histologically verified cases, respectively.
      The patient populations in the two countries were found to be almost identical,
      with an extremely high incidence of germ cell tumors representing 71.2% (in
      Japan) and 80.0% (in Korea) of all pineal region tumors and neuroectodermal
      tumors representing only 15.2% and 16.8%, respectively. The most common type of
      pineal region tumor was germinoma (46.6% in Japan and 47.2% in Korea). The
      majority of tumors were radio- and/or chemosensitive, and adjuvant therapy rather
      than extensive surgery played the major role in the treatment in both countries.
      Radical resection of the tumor was recommended as the initial procedure by only
      22.2% of neurosurgeons in Japan and 16.6% in Korea. Biopsy was recommended by
      38.9% and 50.0%, and radiation therapy by 38.9% and 37.5%, respectively. A
      minimally invasive procedure, by either a neuroendoscopic (33.3% of biopsies in
      Japan) or a stereotactic approach (33.3% of biopsies in Korea), was considered to
      be appropriate as the initial procedure. The study disclosed the almost identical
      epidemiology of this brain tumor in Japan and in Korea and clarified the
      consequent therapeutic modalities. The authors emphasize that minimally invasive
      tissue diagnosis with or without tumor debulking should be considered as the
      initial step for the treatment planning of the pineal region tumor, followed by
      the most commonly indicated major procedures, including radiation therapy,
      chemotherapy and/or radical resection with various methodologies.

PMID- 9548341
TI  - Operative approaches to the pineal region tumors.
AB  - Until the introduction of microsurgery, the surgical treatment of pineal region
      tumors had very poor results with high mortality and morbidity. However, there
      have been remarkable improvements with modern surgical technology and advanced
      knowledge. Now the main surgical approaches to pineal region tumors are the
      occipital transtentorial approach and the infratentorial supracerebellar
      approach. Recently the neuroendoscopic approach has been added. The surgical
      approach and any supplementary treatment should be selected in each case
      according to the nature of the individual tumor. The forms of treatment practiced
      by ourselves, including neuroendoscopic surgery, are presented, and the surgical
      treatments now applied are discussed.

PMID- 9548342
TI  - Pineal tumors: experience with 48 cases over 10 years.
AB  - The authors retrospectively reviewed 48 patients treated at Seoul National
      University Hospital (SNUH) between 1986 and 1995. There were 35 children and 13
      adults, accounting for 10.1% of 345 pediatric and 0.68% of 1914 adult brain
      tumors in SNUH during the same period. The 48 cases consisted of 33 cases of germ
      cell tumor (69%, GCT); 6 of pineoblastoma (PB, 12.5%); 3 of pineocytoma (PC,
      6.3%); 3 of anaplastic astrocytoma (6.3%); 1 of astrocytoma; 1 of glioblastoma;
      and 1 of ependymoma. The median age was 13 years (range 1-59) and the male-to
      female ratio was 3.36:1. The most frequent presenting symptom was due to
      increased intracranial pressure (90%), followed by Parinaud syndrome or diplopia
      (50%). Patients with a benign tumor, such as teratoma (TE), astrocytoma, or
      ependymoma, underwent surgery by the occipital transtentorial approach (OTT) for
      attempted radical resection without adjuvant therapy, while patients with
      immature teratoma (imTE), PC, and anaplastic astrocytoma underwent regional
      radiotherapy (RT) after debulking via OTT. Seven patients with nongerminomatous
      malignant GCT (NG-MGCT) and 3 with germinoma (GE) underwent craniospinal
      radiation only, 6 with GE, a NG-MGCT, and 2 with GE+TE received craniospinal
      radiotherapy (CSRT) after debulking via OTT. Three patients with GE, 4 with NG
      MGCT, and 3 with PB underwent radiochemotherapy after debulking via OTT. Forty
      four patients were followed up after treatment. The median follow-up period was
      36 months. All patients with GE were alive after RT at 36 months (median) of
      follow-up (range 7-70 months). All with GE+TE and TE were alive. Three patients
      with PC or astrocytoma were also alive with stable or no evidence of disease. In
      1 of the 3 cases of imTE there was a recurrence. However, 4 patients with NG-MGCT
      died, all of whom had undergone CSRT only; 2 PB patients were alive (12, 19
      months), 1 in a moribund status (36 months), and 2 were dead (6, 60 months). The
      overall mean survival time with pineal tumors was 66 months and the 3-year
      survival rate was 84% with minimal posttreatment complications. It is concluded
      that pineal region tumors have male and childhood predominances, and the most
      common tumor is GCT. The majority of pineal region tumors are malignant. Pineal
      region tumors can be approached safely and effectively and the surgical
      complications are mostly transient. Their prognosis is dependent on the
      pathologies and treatment modalities.

PMID- 9548343
TI  - Combined treatment with chemotherapy and radiation therapy for intracranial germ
      cell tumors.
AB  - We analyzed our treatment results in 153 patients with histologically verified
      intracranial germ cell tumors and proposed classifying them into three
      therapeutic groups with good prognosis, intermediate prognosis, and poor
      prognosis. In this work, we selected patients treated with chemotherapy
      (cisplatin or carboplatin combinations) in each subgroup, and we discuss the role
      of chemotherapy in their treatment. Our combination chemotherapy regimens are:
      cisplatin-vinblastine-bleomycin, cisplatin-etoposide, and carboplatin-etoposide.
      We delivered these chemotherapies to the last 33 patients and compared their
      treatment results with those obtained in the previous 31 patients, who were
      treated with conventional radiation therapy alone. A combination with
      chemotherapy and a reduced dose of irradiation with local field was given to 7
      patients with germinoma to increase the cure rate and reduce radiation-induced
      side effects, including anterior pituitary dysfunction. We obtained an excellent
      initial response to chemotherapy. The chemotherapy we delivered had significantly
      better effects in the group with intermediate prognosis, but not in the group
      with poor prognosis. More aggressive chemotherapy and radiation therapy should be
      given as the initial treatment.

PMID- 9548344
TI  - Experience with pineal region tumors.
AB  - The results are reported of a retrospective review of the presentation and
      outcome of 43 pineal region tumors treated from 1982 to 1996, including 20
      identified tumors: 5 germinomas, 8 teratomas, 2 embryonal carcinomas, 1
      endodermal sinus tumor, 2 pineocytomas and 2 pineoblastomas. Of the 43 tumors
      reviewed, 36 were located in the pineal region, 5 in the suprasellar, and 2 in
      both the pineal and suprasellar regions. Twenty patients underwent surgical
      resection: total in 6 and partial in 10, while only a biopsy was taken in 4
      cases. Fifteen patients were managed on the basis of serum CSF tumor markers and
      radiation response. Twenty-three patients with germinomas received radiotherapy
      (RT) and had a 5-year survival rate of 87%. Fifteen patients with non
      germinomatous germ cell tumors received RT and chemotherapy following direct
      surgery, and 5 died (mortality rate of 33.3%). The overall survival rate of the
      43 patients with pineal tumors was 79.1% (34/43) and the death rate was 20.9%
      (9/43). It is now recognized that the wide variety of tumor types found in the
      pineal region necessitates different modes of treatment, and improved
      microsurgical and stereotactic surgical techniques have made mortality and
      morbidity rates acceptably low. Because the radiation response and CSF cytology
      are not enough to determine optimum treatment, a tissue diagnosis should be
      obtained in all patients.

PMID- 9548346
TI  - Pigmented medulloepithelioma: report of a case and review of the literature.
AB  - A 9-year-old male child had a IV ventricular medulloepithelioma of classical
      histology, showing tubulopapillary and undifferentiated areas. The unusual
      feature, however, was the presence of melanin pigmentation in the cells, which
      was further confirmed by electron microscopy. So far 28 cases of
      medulloepithelioma have been reported in the English literature. However, none of
      them showed melanin pigmentation. To the best of our knowledge this is the first
      case of pigmented medulloepithelioma in the English literature.

PMID- 9548345
TI  - Intracranial dural cyst.
AB  - Intracranial dural cyst is a very rare congenital malformation. The presence of
      such a cyst was confirmed by means of computed tomography and magnetic resonance
      findings in a child with an enlargement of the head and developmental retardation
      and confirmed histologically in surgically obtained specimens of cyst wall.

PMID- 9548347
TI  - Primary giant granulomatous basal meningitis: an unusual presentation of
      tuberculosis.
AB  - A case of granulomatous tuberculous meningitis in a 3-year-old child without any
      known primary disease in any other organ is presented. Tuberculous meningitis is
      an uncommon presentation of tuberculosis and is characterized by diffuse or
      circumscribed granulomatous involvement of the meninges, particularly at the base
      of the brain. Early diagnosis and treatment are essential to prevent the worst
      events it can bring and to improve the chances of survival. Diagnosis remains
      difficult because of the lack of reliable clinical diagnostic criteria.

PMID- 9548348
TI  - Multiple intracranial aneurysms in a patient with Seckel syndrome.
AB  - A 17-year-old girl affected by Seckel syndrome and multiple intracranial
      aneurysms is reported. Cerebral hemorrhage was the reason for the diagnostic work
      up. The aneurysms were surgically treated. The main features of the syndrome,
      technical problems encountered during surgery and the prognosis of this condition
      are discussed.

PMID- 9548349
TI  - Surgically treated traumatic synchondrotic disruption of the odontoid process in
      a 15-month-old girl.
AB  - A case of traumatic synchondrotic disruption in a 15-month-old girl is reported;
      she was treated with interlaminar wiring of C1-C2 without grafting. Reduction of
      the dislocation and angulation and stability were achieved without evidence of
      growth disturbance. However, the child's initial poor neurological status with
      tetraplegia below the level of C7 remained unchanged. Besides our case, there are
      only three other cases in the literature of young children primarily operated on
      for a traumatic odontoid synchondrotic disruption. Even though the dorsal
      interlaminar wiring of C1-C2 without grafting is an easy and safe procedure even
      in the very young, the optimal form of treatment for this rare injury is still
      unsettled.

PMID- 9548350
TI  - Crisis: what crisis?
AB  - There is a large economic cost associated with low back pain. In 1994 its cost to
      the United Kingdom (UK) was estimated by the UK Clinical Standards Advisory Group
      report to be nearly pound sterling 6,000 million (ECU 8,350 million) annually.
      This principally consists of the indirect costs of lost production and disability
      payments rather than direct health service costs. A re-examination of the
      assumptions in the report shows that these costs appear to overestimate the
      economic cost of back pain by an unquantified, but possibly large, amount. This
      may restrict the benefit of introducing more effective treatments for back pain.

PMID- 9548351
TI  - Gait analysis in idiopathic scoliosis before and after surgery: a comparison of
      the pre- and postoperative muscle activation pattern.
AB  - In a prospective experimental study the level gait activity scores of the
      iliocostalis lumborum, glutaeus medius, tensor fasciae latae, vastus lateralis
      and peronaeus longus muscles of both body sides were examined by computerized
      electromyography in 23 patients with idiopathic scoliosis before and after CD
      instrumentation. The pre- and postoperative findings were examined as to
      asymmetric patterns in muscle requisition during gait and the respective changes
      induced by the spinal correction. These results were compared with the
      corresponding results obtained in healthy subjects in two independent sessions
      with identical experimental conditions. A muscle activity asymmetry coefficient
      was defined to quantify the degree of left/right muscle activation asymmetry
      observed. Postoperatively a statistically significant reduction (P < 0.05) of a
      preoperatively strongly increased activity was found in the lumbar muscles of the
      convex side of double major scolioses as well as in the glutaeus medius and
      tensor fascia lata muscles of the concave side of thoracic curvatures. Both the
      casuistic and statistical analysis of the results of our study support the
      hypothesis that activity asymmetries observed in the paravertebral musculature in
      idiopathic scoliosis patients are the result of the scoliotic body deformities,
      with consequent asymmetries in the biomechanical force patterns of body postures
      and body motions, rather than an aetiological factor of scoliotic curvatures.

PMID- 9548353
TI  - Characterization of the mechanical behaviour parameters of the costo-vertebral
      joint.
AB  - This in vitro study introduces a new method to determine quantitative parameters
      characterizing the mechanical behaviour of the costo-vertebral joint. These
      parameters are useful in building numerical models of the thoracic spine, taking
      into account the thoracic cage. Nine thoracic cages were isolated from fresh
      human cadavers. From each cage, three functional units were tested: T1-T2, T5-T6,
      T9-T10. Loads were applied according to the joint local coordinate system. Every
      functional unit was tested first intact and again after section of successive
      costo-transverse ligaments. We used an opto-electronic system to follow the three
      dimensional motion of the joint, and obtained non-linear load/displacement curves
      according to the primary rotation axis. A statistical analysis of these curves
      allowed the calculation of parameters describing the joint mechanical behaviour:
      total range of motion, motion in the low-stiffness zone, and flexibilities in the
      positive and negative quasi-linear zones. These values can be used as a database
      for mechanical modeling of the spine.

PMID- 9548352
TI  - Quantification of cosmesis for patients affected by adolescent idiopathic
      scoliosis.
AB  - The aim of this study was to quantify cosmesis for patients affected by
      adolescent idiopathic scoliosis. Eight nonmedical judges were asked to examine
      photographs of 40 patients with adolescent idiopathic scoliosis, and to score the
      cosmesis of their backs without any information. Various parameters were measured
      from radiographs, Moire topographies, and physical measurements of patients, and
      these were compared with the cosmetic scores of the judges. The judges' scoring
      proved to be reliable. The cosmetic scores showed a significant correlation with
      the Cobb angle, hump severity, asymmetry of the waist line, circumference of the
      chest, and obesity. Multivariate analysis produced equations to calculate the
      cosmetic score for the back. This equation is thought to have a useful clinical
      application.

PMID- 9548354
TI  - Lumbar disc herniation: favourable outcome associated with intake of wine.
AB  - Recent research indicates that non-smoking and intake of alcoholic beverages, in
      particular wine, are associated with beneficial effects on several diseases,
      especially atherosclerosis. The aim of the study was to investigate whether
      smoking or the intake of different alcoholic beverages are associated with the
      outcome 2 1/2 years after first-time lumbar disc surgery. The design was a follow
      up study, using a questionnaire including a rating scale. All 170 patients
      consecutively operated upon for a lumbar disc herniation over a 1-year period
      were clinically examined at the time of the operation and classified according to
      various social and demographic variables. The main outcome measure, 2 1/2 years
      after, was the total rating score, i.e. the sum of three equally weighted outcome
      measures: pain, impairment and self-assessment of the operation result. The
      questionnaires were completed by 148 patients (87%). The median age of patients
      was 41 years; 60 of them were women. Fifty-four per cent were smokers and 42%
      wine drinkers. Logistic regression analysis calculated a fourfold increase in the
      success rate for wine drinkers. This fourfold odds ratio was not significantly
      reduced by the following variables: age, sex, social class, household income,
      smoking habits, employment status or marital status. Smoking could not be shown
      to be an independent risk factor for the outcome. Intake of wine was found to be
      associated with a good prognosis after first-time lumbar disc surgery, and this
      association could not be attributed to the lifestyle characteristics studied.

PMID- 9548355
TI  - Fitness for work after surgery for lumbar disc herniation: a retrospective study.
AB  - This report retrospectively evaluates fitness for work in 3956 cases of surgery
      for lumbar disc herniation between 1992 and 1994. Patient records were derived
      from a database including all interventions of the insured population of the
      largest Belgian sickness fund. The datafile consisted of 126 cases of
      percutaneous nucleotomy (nucleotomy group), 286 cases of lumbar disc surgery with
      fusion (fusion group) and 3544 cases of standard lumbar disc surgery (standard
      group). Fitness to resume work within 12 months after intervention was obtained
      in about 70% of the patients in the standard and nucleotomy groups but in only
      45% of the patients in the fusion group. Ten medicosocial factors were related to
      fitness for work as outcome measure. Incapacity for work more than 12 months
      after intervention was defined as a bad outcome. Logistic regression was used to
      test the combined relative significance of the different variables. For the
      standard group a long duration of work incapacity before intervention, older age,
      lower benefit, employment as a blue-collar worker, a long duration of hospital
      stay and unemployment were significantly associated with a poor outcome. Related
      factors for the fusion group were a long duration of work incapacity before
      operation, a long duration of hospital stay and unemployment. For the nucleotomy
      group, no factor was significantly associated with a poor outcome. For the total
      group, discectomy combined with fusion was significantly related to a poor
      outcome whereas a standard discectomy and a percutaneous nucleotomy did not
      differ in their impact on fitness for work.

PMID- 9548356
TI  - Effects on the vertebral end-plate of uncomplicated lumbar discography: an MRI
      study.
AB  - The study aimed to identify and characterise changes occurring in the vertebral
      end-plate on MRI following uncomplicated lumbar discography. MRI was performed
      immediately before and within 2 h after uncomplicated lumbar discography in 20
      consecutive patients undergoing the study as a precursor to possible spinal
      fusion. Of these, seven patients underwent a further MRI study at a mean of 72
      days after discography (range 19-183 days). The MRI scans were assessed for the
      presence of any changes in the end-plates prior to and following discography. End
      plate changes were identified in eight patients (40%) prior to discography. No
      new changes in end-plate signal intensity (SI) were identified in either the
      immediate or delayed MRI studies. The study suggests that any changes occurring
      in the vertebral end-plate following discography should be considered due to
      infectious discitis. There is no support for the concept of chemical discitis,
      chemical irritation of bone or microfracture of subchondral trabeculae as a cause
      of pain at discography.

PMID- 9548357
TI  - The relationship between vertebral body deformity and disc degeneration in lumbar
      spine of the senile.
AB  - This study provides an investigation of the relationship between vertebral
      deformities and disc degeneration in patients with senile osteoporosis using
      biomechanical and medical imaging methods. The finite element analysis showed
      that stress concentration in the central area of the vertebral body is much
      decreased with disc degeneration, indicating that load transmission has been
      altered. Radiography and MRI suggested that vertebral deformities are related to
      the height and degeneration of the disc just below this vertebral body. When a
      disc has decreased height or degeneration, the vertebral body just above it is
      less likely to be deformed for patients with spinal osteoporosis.

PMID- 9548358
TI  - Calcium pyrophosphate dihydrate deposition in degenerate lumbar discs.
AB  - Calcium pyrophosphate dihydrate (CPPD) crystal deposition in lumbar
      intervertebral discs has been described, but its clinical significance remains
      unclear. The present study analyzed histological sections of lumbar discs that
      were obtained from patients undergoing anterior lumbar interbody fusion.
      Immunohistological staining was undertaken to identify neural elements and blood
      vessels. Patients with CPPD deposition were compared with a group without CPPD
      deposition undergoing the same operation. CPPD was found in 15.7% of investigated
      patients (12.6% of analyzed discs). Deposits were found in areas of the annulus
      and nucleus showing advanced degeneration. Two patterns were identified: one
      comprised sharply demarcated rounded deposits, while the other showed diffuse
      deposition of crystals. There was no association with ingrowth of vascular or
      neural tissue. Clinical data did not differ significantly in the two groups of
      patients. However, in all patients with CPPD deposition there was a history of
      trauma, previous surgery, or both. Isolated CPPD deposition in lumbar
      intervertebral discs appears to be an incidental finding that is not related to
      systemic diseases or general arthropathies.

PMID- 9548359
TI  - Vertebral osteomyelitis: an analysis of 38 surgically treated cases.
AB  - The purpose of the study was to evaluate the characteristics of patients with
      vertebral osteomyelitis who were treated by anterior debridement and interbody
      fusion. Thirty-eight patients with vertebral osteomyelitis, who were treated
      between 1980 and 1993, were analyzed in terms of age at the occurrence of
      disease, duration of disease, type of onset symptoms, radiological type of
      vertebral destruction, species of pathogen, and surgical result. Thirty-one out
      of 38 patients (82%) were more than 40 years of age. The patients with severe
      vertebral destruction were significantly older than those with mild vertebral
      destruction. Vertebral destruction in the thoracic spine was significantly more
      severe than that in the lumbar spine. Staphylococcus aureus was identified in
      only six patients (32% of organism-determined cases). In the present patients who
      required anterior debridement and bone grafting for this disease, the prognosis
      was quite good after anterior interbody fusion in conjunction with antibiotics
      therapy.

PMID- 9548360
TI  - Vertigo in patients with cervical spine dysfunction.
AB  - To our knowledge, quantitative studies on the significance of disorders of the
      upper cervical spine as a cause of vertigo or impaired hearing do not exist. We
      examined the cervical spines of 67 patients who presented with symptoms of
      dizziness. Prior to the orthopaedic examination, causes of vertigo relating to
      the field of ENT and neurology had been ruled out. Fifty patients of the above
      mentioned group were studied. They followed the outlined treatment protocol with
      physical therapy and were available for 3 months of follow-up. Thirty-one
      patients, hereinafter referred to as group A, were diagnosed with dysfunctions of
      the upper cervical spine. Nineteen patients, hereinafter referred to as group B,
      did not show signs of dysfunction. Cervical spine dysfunctions were documented as
      published by Bischoff. In group A dysfunctions were found at level C1 in 14
      cases, at level C2 in 6 cases and at level C3 in 4 cases. In seven cases more
      than one upper cervical spine motion segment was affected. Dysfunctions were
      treated and resolved with mobilising and manipulative techniques of manual
      medicine. Regardless of cervical spine findings seen at the initial visit, group
      A and B patients received intensive outpatient physical therapy. At the final 3
      month follow-up, 24 patients of group A (77.4%) reported an improvement of their
      chief symptom and 5 patients were completely free of vertigo. Improvement of
      vertigo was recorded in 5 group B patients (26.3%); however, nobody in group B
      was free of symptoms. We concluded that a functional examination of motion
      segments of the upper cervical spine is important in diagnosing and treating
      vertigo, because a non-resolved dysfunction of the upper cervical spine was a
      common cause of long-lasting dizziness in our population.

PMID- 9548361
TI  - Three-dimensional measurement of wedged scoliotic vertebrae and intervertebral
      disks.
AB  - Idiopathic scoliosis involves complex spinal intrinsic deformations such as the
      wedging of vertebral bodies (VB) and intervertebral disks (ID), and it is obvious
      that the clinical evaluation obtained by the spinal projections on the two
      dimensional (2D) radiographic planes do not give a full and accurate
      interpretation of scoliotic deformities. This paper presents a method that allows
      reconstruction in 3D of the vertebral body endplates and measurement of the 3D
      wedging angles. This approach was also used to verify whether 2D radiographic
      measurements could lead to a biased evaluation of scoliotic spine wedging. The 3D
      reconstruction of VB contours was done using calibrated biplanar X-rays and an
      iterative projection computer procedure that fits 3D oriented ellipses of
      adequate diameters onto the 3D endplate contours. "3D wedging angles" of the VB
      and ID (representing the maximum angle between adjacent vertebrae) as well as
      their angular locations with respect to the vertebral frontal planes were
      computed by finding the positions of the shortest and longest distances between
      consecutive endplates along their contour. This method was extensively validated
      using several approaches: (1) by comparing the 3D reconstructed endplates of a
      cadaveric functional unit (T8-T9) with precise 3D measurements obtained using a
      coordinate measuring machine for 11 different combinations of vertebral angular
      positions; (2) by a sensitivity study on 400 different vertebral segments
      mathematically generated, with errors randomly introduced on the digitized points
      (standard deviations of 0.5, 1, 2, and 3 mm); (3) by comparing the clinical
      wedging measurements (on postero-anterior and lateral radiographs) at the
      thoracic apical level of 34 scoliotic patients (15 degrees < Cobb < 45 degrees)
      to the computed values. Mean errors for the 11 vertebral positions were 0.5 +/-
      0.4 mm for VB thickness, less than 2.2 degrees for endplate orientation, and
      about 11 degrees (3 mm) for the location of the maximum 3D wedging angle along
      the endplate contour. The errors below 2 mm (introduced on the digitized points)
      slightly affected the 3D wedging angle (< 2 degrees) and its location (< 4
      degrees) for the ID. As for the clinical evaluation, average angular errors were
      less than 0.4 degrees in the radiographic frontal and lateral planes. The mean 3D
      wedged angles were about 4.9 degrees +/- 1.9 degrees for the VB and 6.0 degrees
      +/- 1.7 degrees for the ID. Linear relations were found between the 2D and the 3D
      angles, but the 3D angles were located on diagonal planes statistically different
      than the radiographic ones (between 100 degrees and 221 degrees). There was no
      statistical relation between the 2D radiographic angles and the locations of the
      3D intervertebral wedging angles. These results clearly indicate that VB and ID
      endplates are wedged in 3D, and that measurements on plain radiographs allow
      incomplete evaluation of spinal wedging. Clinicians should be aware of these
      limitations while using wedging measurements from plain radiographs for diagnosis
      and/or research on scoliotic deformities.

PMID- 9548362
TI  - Harvesting and preparation of cadaveric osseoligamentous lower cervical spine (C2
      C7) for biomechanical testing.
AB  - Cadaveric osseoligamentous lower cervical spines (C2-C7) are often used in the
      investigation of spinal biomechanics in vitro. Surprisingly, however, the
      techniques of harvesting at postmortem and preparation of cadaveric
      osseoligamentous lower cervical spine for biomechanical testing have not been
      described in detail. We describe a simple and effective method that can be
      readily integrated into the routine autopsy procedure. Points on the avoidance of
      disfiguring the cadaver and damaging the spinal osseoligamentous structures are
      highlighted.

PMID- 9548364
TI  - Unrecognized laceration of main bronchus caused by fracture of the T6 vertebra.
AB  - We report on an extremely rare case of a 58-year-old male polytraumatized patient
      who sustained a bursting fracture of the T6 vertebral body associated with
      laceration of the posterior wall of the right main bronchus from the spiculae of
      the vertebral body fragments. The patient was on admission asymptomatic until he
      underwent an endotracheal anesthesia for stabilization of associated fractures of
      the extremities, when he developed acute respiratory disturbances. The opening of
      the bronchus was repaired via a thoracotomy, while the spine was successfully
      supported with a custom-made brace for 3 months. In the 3-year follow-up
      evaluation, the patient did well and suffered no complaints of the spine or
      lungs. Spine surgeons should be aware of this rare complication, which may
      accompany bursting fractures in the midthoracic spine. Laceration of the bronchus
      should be suspected when fragments of the vertebral body are dislocated far
      anteriorly.

PMID- 9548365
TI  - Occipitoatlantal instability associated with articular tropism.
AB  - The authors report the case of a patient with rotatory posterior subluxation of
      the occiput on the atlas associated with tropism of the O-C1 articulations.
      Lateral flexion-extension plain films demonstrated 5 mm of posterior translation
      of the occiput on the atlas. Tomographs revealed tropism of the O-C1
      articulations, and CT scans on extension demonstrated posterior rotatory
      subluxation of the occiput on the atlas. The patient had no osseous abnormality
      caudally below the atlantoaxial joint, and underwent posterior occipitoatlantal
      fusion by wiring. At the 4-year follow-up, the grafted bone had been
      incorporated, and the patient was completely free from preoperative symptoms. In
      the present patient, occipitoatlantal instability is presumed to have derived
      from articular tropism.

PMID- 9548363
TI  - Increased kyphosis by a combination of fractures of the sternum and thoracic
      spine.
AB  - A 67-year-old patient suffered a fall and sustained injuries to the thorax,
      combined with fractures of the ribs, sternum and thoracic spine. Her pre-existing
      kyphosis (caused by osteoporotic vertebral collapse) increased in severity. There
      was a clear relationship between a sternal fracture, deterioration of thoracic
      kyphosis and a fracture of the thoracic spine.

PMID- 9548366
TI  - Tubular peroxisomes in HepG2 cells: selective induction by growth factors and
      arachidonic acid.
AB  - We showed recently the plasticity of the peroxisomal compartment in the human
      hepatoblastoma cell line HepG2 as evidenced by the presence of elongated tubular
      peroxisomes measuring up to 5 microm next to much smaller spherical or rod-shaped
      ones (0.1-0.3 microm). Since the occurrence of tubular peroxisomes in a given
      cell in culture is synchronized, with neighboring cells containing either small
      spherical or elongated tubular peroxisomes, cell counting of immunofluorescence
      preparations stained for catalase was used for the quantitative assessment of the
      dynamics of the peroxisomal compartment and the factors regulating this process.
      Initial studies revealed that the formation of tubular peroxisomes is primarily
      influenced by the cell density as well as by lipid- and protein-factors in fetal
      calf serum, being independent of an intact microtubular network. Biochemical
      studies showed that the occurrence of tubular peroxisomes correlated with the
      expression of the mRNA for 70 kDa peroxisomal membrane protein (PMP70), but not
      with that of matrix proteins. By cultivation of cells in serum- and protein-free
      media specific factors were identified which influenced the formation of tubular
      peroxisomes. Among several growth factors tested, nerve growth factor (NGF) was
      the most potent one inducing tubular peroxisomes and its effect was blocked by
      K252b, a specific inhibitor of neurotrophin receptor pathway, suggesting the
      involvement of signal transduction in this process. Furthermore, from several
      polyunsaturated fatty acids (PUFA) which all induced tubular peroxisomes, the
      arachidonic acid (AA) was the most potent one. Our observations suggest that
      tubular peroxisomes are transient structures in the process of rapid expansion of
      the peroxisomal compartment which are induced either by specific growth factors
      or by polyunsaturated fatty acids both of which are involved in intracellular
      signaling.

PMID- 9548367
TI  - Tyrosine and serine phosphorylation of the neural cell adhesion molecule L1 is
      implicated in its oligomannosidic glycan dependent association with NCAM and
      neurite outgrowth.
AB  - We have previously shown that a cis interaction between the cell adhesion
      molecules L1 and NCAM is mediated by N-linked oligomannosidic glycans carried by
      L1 and that this L1/NCAM association is involved in basal neurite outgrowth from
      early postnatal cerebellar neurons of mouse brain [R. Horstkorte et al., J. Cell
      Biol. 121, 1409-1421 (1993)]. Extending these earlier studies we investigated
      signal transduction mechanisms elicited by this molecular interaction. We show
      here that phosphorylation of L1 is reduced concomitant with reduced neurite
      outgrowth when the L1/NCAM interaction is inhibited by oligomannosidic
      glycopeptides. Similarly, when a peptide of the 4th immunoglobulin (Ig)-like
      domain of NCAM - representing part of NCAM's carbohydrate-binding site - was
      added to the culture medium of the cells, neurite outgrowth and phosphorylation
      of L1 was strongly reduced. No effect on neurite outgrowth and phosphorylation of
      L1 was observed when cells were maintained in the presence of a peptide
      comprising part of the 1st Ig-like domain of NCAM or in the presence of the
      peptide encoded by the variable alternative spliced exon (VASE), which is also
      located in the 4th Ig-like domain of NCAM. Furthermore, phosphorylation of
      tyrosine and serine residues of L1 is reduced when the L1/NCAM interaction at the
      cell surface of cerebellar neurons is perturbed. Our observations suggest that a
      signal transduction mechanism is implicated in basal neurite outgrowth in which
      both tyrosine and serine phosphorylation of L1 represent a possible proximal
      step. Some of these results were presented at the International Glycoconjugate
      Symposium in Seattle, USA [P. C. Heiland et al., Glycoconj. J. 12, 521(1995)].

PMID- 9548369
TI  - Characterization of monoclonal antibodies against cell wall epitopes of the
      insect pathogenic fungus, Nomuraea rileyi: differential binding to fungal
      surfaces and cross-reactivity with host hemocytes and basement membrane
      components.
AB  - Monoclonal antibodies (MAbs) were generated against epitopes on yeast-like hyphal
      bodies and hyphae of the entomopathogenic hyphomycete, Nomuraea rileyi. Two MAbs
      (4C10, 2H4) bind to epitopes common to both hyphal bodies and hyphae, whereas MAb
      4E9 binds only to hyphal surfaces. 4C10 and 2H4 appear to be directed towards
      carbohydrate portions of cell surface mannoproteins, as evidenced by similarities
      in staining patterns between these MAbs and Concanavalin A on Western blots of N.
      rileyi cell wall extracts. These MAbs cross-react with antigens on blastospore
      and hyphal surfaces of two other entomopathogenic fungi, Beauveria bassiana and
      Paecilomyces farinosus in fluorescence microscopy assays, but do not cross-react
      with a non-entomopathogenic strain of Candida albicans or with Saccharomyces
      cerevisiae yeasts. MAb 4C10 also cross-reacts with immunocompetent granular
      hemocytes from Spodoptera exigua (beet armyworm) and Trichoplusia ni (cabbage
      looper) larvae and with S. exigua plasmatocytes. Electron microscopy revealed
      that this MAb binds to a component in cytoplasmic granules in the hemocytes, and
      that surface labeling may be due to the release of this MAb-positive component
      upon degranulation. MAb 2H4 does not cross-react with granular hemocytes, but
      does bind to plasmatocytes and hemocytes that tightly adhere to the substrate in
      monolayer assays. Additionally, MAb 4C10 specifically labels a basement membrane
      epitope on S. exigua fat body, suggesting that this antibody binds to mannose
      residues on extracellular matrix glycoproteins. Cross-reactivity of these N.
      rileyi MAbs with insect hemocyte and tissue components indicates that fungal
      surface epitopes can mimic host surface molecules, which could explain why N.
      rileyi hyphal bodies are not recognized by granulocytes and are able to circulate
      freely in the hemolymph without binding to basement membranes lining the
      hemocoel.

PMID- 9548368
TI  - Beta1B integrin interferes with matrix assembly but not with confluent monolayer
      polarity, and alters some morphogenetic properties of FRT epithelial cells.
AB  - Beta1B is a beta1 integrin splice variant that differs from the ubiquitous beta1A
      in the terminal portion of the cytosolic tail. The expression of this variant in
      CHO cells results in reduced fibroblast adhesion and motility (Balzac, E et al.,
      J. Cell Biol. 127, 557-565 (1994)). We have evaluated the phenotypic changes
      induced by the expression of beta1B in the FRT epithelial cell line. Stable
      transfectants of FRT cells expressing beta1B or beta1A human integrins were
      obtained. The transfected integrins associated with the endogenous alpha subunits
      and were delivered to the plasma membrane. Beta1B expressing cells attached less
      efficiently and spread less on fibronectin, laminin or type IV collagen coated
      dishes. A great reduction of fibronectin fibrils associated to the basal membrane
      of non-confluent beta1B transfected cells was observed. This was paralleled by
      the disappearance of microfilament bundles and loss of basally located focal
      adhesions. On the contrary, upon beta1A transfection, a higher amount of
      fibronectin fibrils, together with microfilament bundles and focal adhesions, was
      observed. Expression of beta1B did not significantly modify the ability to
      manifest the polarized phenotype when cells were grown to confluence on filters
      in two-chamber-systems. Beta1B-transfected cells showed reduced motile properties
      when embedded as aggregates in type I collagen gels. Moreover, formation of
      polarized cysts in suspension culture was impaired. The results show that beta1B,
      by interfering with focal adhesion organization, microfilament and fibronectin
      assembly, cell spreading and migration, affects some morphogenetic properties of
      FRT epithelial cells.

PMID- 9548370
TI  - Adenosine inhibits actin dynamics in human neutrophils: evidence for the
      involvement of cAMP.
AB  - The mechanisms by which adenosine regulates the inflammatory reaction are poorly
      characterized. In this study, we investigated the effects of adenosine on
      neutrophil actin polymerization elicited by the chemotactic peptide N-formyl
      methionyl-leucyl-phenylalanine (fMLP) or IgG-opsonized yeast particles. We used
      bodipy-phallacidin staining in combination with flow cytometry and found that
      adenosine markedly reduced actin polymerization triggered by IgG-yeast, whereas
      the effect on the fMLP-response was less pronounced. Similar or even more
      pronounced effects were obtained with the adenosine A2 receptor agonist 5'-N
      ethylcarboxamidoadenosine (NECA), suggesting an A2 receptor-mediated mechanism.
      The following observations indicate that the A2 receptor-induced effects involve
      the cAMP-protein kinase A (PKA) signaling pathway: (1) a combination of NECA and
      the cAMP-specific phosphodiesterase (PDE) inhibitor Ro 20-1724 raised the cAMP
      content in both unstimulated and stimulated neutrophils and also further
      inhibited the actin dynamics; (2) the PKA inhibitor H89 reversed the inhibitory
      effects of NECA on the actin dynamics; (3) Ro 20-1724, isoproterenol and
      dibutyryl cAMP (DBcAMP) reduced actin polymerization in almost the same way as
      NECA did. NECA together with Ro 20-1724 impaired the fMLP-induced shape changes
      and cortical accumulation of actin filaments. In contrast, H89 potentiated the
      fMLP-induced formation of a submembranous ring of actin filaments. Neutrophils
      phagocytosing yeast particles in the presence of NECA and Ro 20-1724 were
      predominantly round in shape, and their ability to extend actin-rich pseudopods
      around the prey was reduced. These effects were partly antagonized by H89. In
      correlation with the effects on actin polymerization, NECA more effectively
      diminished IgG-induced upregulation of the beta2 integrin CD11b/CD18 than such
      upregulation induced by fMLP. The inhibitory effects of A2-receptor activation on
      actin dynamics and beta2 integrin expression in neutrophils exposed to IgG-yeast
      were also associated with a cAMP-dependent reduction of the phagocytic capacity.
      In conclusion, we show that adenosine inhibits actin dynamics and shape changes
      in neutrophils via a cAMP-dependent pathway. This finding further characterizes
      the mechanisms by which adenosine functions as an important modulator of the
      inflammatory response.

PMID- 9548371
TI  - Changes in kinesin distribution and phosphorylation occur during regulated
      secretion in pancreatic acinar cells.
AB  - In secretory cells, microtubule- (Mt-) based motor enzymes are thought to support
      transport of secretory vesicles to the cell surface for subsequent release. At
      present, the role of Mts and kinesin in secretory vesicle transport in exocrine
      epithelial cells has not been defined. Furthermore, it is unclear whether an
      agonist-induced secretory event modifies kinesin function and distribution, thus
      altering vesicle transport. To this end, we utilized isolated rat pancreatic
      acini and cultured rat pancreatic acinar cells to examine the role of Mts and
      kinesin in regulated secretion. Exposure of cells to cytoskeletal antagonistic
      drugs demonstrated that the observed movements of apically clustered zymogen
      granules (ZGs) are supported by Mts, but not actin. Morphological studies of Mt
      organization in polarized acini show that Mt plus ends extend outward from the
      apical membrane toward the cell center. Immunofluorescence microscopy in both
      cell models revealed a clear association of kinesin with apical ZGs, while
      quantitative immunoblot analysis of pancreatic subcellular fractions confirmed
      kinesin enrichment on ZG membranes. In addition, microinjection of kinesin
      antibodies into cultured acinar cells inhibited ZG movements. Indirect
      immunofluorescence staining of isolated cells and quantitative Western blotting
      of isolated ZGs revealed that kinesin association with granule membranes
      increased up to 3-fold in response to a secretory stimulus. Autoradiographic
      studies of 32P-labeled acini showed up to a 6-fold increase in kinesin heavy
      chain (KHC) phosphorylation during stimulated secretion. These studies provide
      the first direct evidence that Mts and kinesin support ZG movements and that
      physiological agonists induce a marked phosphorylation of KHC while increasing
      the association of kinesin with ZG membranes. These changes during agonist
      stimulation suggest that the participation of kinesin in zymogen secretion is
      regulated.

PMID- 9548372
TI  - Acinar lumen pH regulates endocytosis, but not exocytosis, at the apical plasma
      membrane of pancreatic acinar cells.
AB  - A two-step exocytosis/endocytosis protocol was used in rat pancreatic acini to
      study membrane trafficking events at the apical plasma membrane (APM) as a
      function of extracellular pH. Exocytosis, as measured by cholecystokinin (CCK)-8
      induced release of amylase into the incubation medium, was relatively insensitive
      to changes in extracellular pH from 5.5 to 9.0. In contrast, endocytosis, as
      measured by temperature-dependent uptake of horseradish peroxidase (HRP), was
      robust at pH values between 6.5 and 8.3 but abolished at acidic pH values of 5.5
      to 6.0. Energy metabolism and cell viability were maintained during pH 6-induced
      cessation of HRP uptake, and the vesicular block could be reversed upon raising
      the luminal pH to 7.4. Histochemical and morphometric studies of HRP uptake
      examined by electron microscopy indicated that extracellular pH regulates
      endocytosis at the apical plasma membrane. At pH 6.0 in prestimulated cells, HRP
      uptake at the APM was abolished, and acinar lumen membranes remained markedly
      dilated with decreased density of microvilli and "arrested" exocytic images. At
      pH 7.4, HRP was taken up into endolysosomal structures within the Golgi complex,
      and acinar lumen membranes were contracted. Cleavage of GP2, a glycosyl
      phosphatidylinositol-anchored protein, was associated with the pH-dependent
      activation of HRP uptake. These studies demonstrate that acinar lumen pH
      regulates endocytic but not exocytic activity at the APM and suggest that
      alkalinization of the acinar lumen by duct cells is required for retrieval of
      exocytic membranes into the acinar cell via vesicular uptake mechanisms. The role
      of acid-base interactions within the acinar lumen provides a novel basis for
      understanding the cellular and luminal defects observed within the exocrine
      pancreas in cystic fibrosis.

PMID- 9548373
TI  - Cleavage of GPI-anchored proteins from the plasma membrane activates apical
      endocytosis in pancreatic acinar cells.
AB  - Using rat pancreatic acini, we have recently shown that apical endocytosis is
      inhibited at pH 6.0 and progressively activated as the pH is increased to 8.3.
      Endocytotic activity correlated with the release of GP2, a GPI-linked protein,
      from the apical plasma membrane. To determine whether the cleavage of GPI
      anchored proteins from the membrane of rat acinar cells was responsible for
      activation of endocytosis, cells at pH 6.0 were incubated with PI-specific
      phospholipase C (PI-PLC). PI-PLC treatment reversed the inhibition of endocytosis
      observed at pH 6.0. Reactivation of endocytosis correlated with PI-PLC-induced
      release of GP2 but not cleavage of phospholipids in cellular membranes.
      Furthermore, administration of diacylglycerol or phorbol esters had no effect on
      reactivation of endocytosis. PI-PLC did not alter intracellular pH or calcium
      levels. Two proteins were identified as GPI-linked proteins on the cell surface.
      One was GP2, whose release from the apical plasma membrane correlated with apical
      endocytosis of horseradish peroxidase (HRP). The other protein, identified by
      Western blotting using an antibody directed against a cryptic determinant exposed
      on GPI-linked proteins after cleavage with PI-PLC, has a molecular weight of
      98000 in nonreducing SDS gels and 54000 in reducing SDS gels. By nondenaturing
      gel electrophoresis and staining with naphthylphosphate, this protein was found
      to be alkaline phosphatase. In contrast to GP2, alkaline phosphatase was not
      endogenously released at pH values of 7.4 or 8.3, conditions that activate
      endocytosis of HRP under physiological conditions. By electron microscopic
      evaluation, incubation of cells at pH 6.0 with PI-PLC led to induction of HRP
      uptake into vesicles at the apical pole of the cell, a reduction in apical plasma
      membranes, and a concomitant contraction of the acinar lumen space. Internalized
      HRP accumulated in the Golgi region of the cell. These results suggest that the
      cleavage of GPI-anchored proteins from the apical plasma membrane activates
      apical endocytosis.

PMID- 9548374
TI  - The SURF-6 protein is a component of the nucleolar matrix and has a high binding
      capacity for nucleic acids in vitro.
AB  - The recently identified novel protein SURF-6 is shown to be a component of the
      nucleolar matrix. Immunofluorescence analysis demonstrated that SURF-6 was
      localized in residual nucleoli of in situ nuclear matrix preparations of mouse
      fibroblast cells (NIH 3T3), which were depleted of soluble and chromatin related
      proteins. Immunoblot analysis of biochemical nucleolar subfractions confirmed
      that SURF-6 was present in the nucleolar matrix fraction, and was absent from the
      fractions of soluble proteins released by DNase or RNase. The capacity of SURF-6
      to bind nucleic acids was investigated in vitro. Both endogenous SURF-6 from
      nuclear extracts and recombinant SURF-6 exhibited a strong binding capacity for
      nucleic acids. It was shown that SURF-6 bound to both DNA and RNA, however, it
      showed stronger binding to RNA. The presence and nuclear distribution of SURF-6
      during the cell cycle was explored by immunofluorescence analysis. It was shown
      that SURF-6 was always found in the nucleolus regardless of the phase of the cell
      cycle suggesting that it is a structural protein constitutively present in
      nucleolar substructures. The colocalization of SURF-6 with the major nucleolar
      proteins B23 and fibrillarin, which are known to be involved in the processing of
      ribosomal RNA (rRNA), was examined both in interphase and mitosis by double
      immunolabeling of cells. SURF-6 was found to be largely coincident with both
      proteins in interphase and it was distributed in the same cellular locations,
      namely the perichromosomal layer, the cytoplasm and prenucleolar bodies, in
      mitosis. However, colocalization of SURF-6 with fibrillarin and B23 was only
      partial in interphase, and the dynamics of its localization was not completely
      the same as those of either fibrillarin or B23 during mitosis. Taken together,
      these results indicate that SURF-6 is a novel nucleolar matrix component and
      imply that SURF-6 might support nucleolar matrix structure and function(s) via
      its association with nucleic acids. We propose that SURF-6 may be involved in
      processing of rRNA, based on its cytological characteristics, but at stages in
      ribosomal biogenesis which are different from those for fibrillarin and B23.

PMID- 9548375
TI  - Effects of genic substitution at the agouti, brown, albino, dilute, and pink-eyed
      dilution loci on the proliferation and differentiation of mouse epidermal
      melanocytes in serum-free culture.
AB  - To examine the effects of coat-color genes on the proliferation and
      differentiation of mouse epidermal melanocytes, we cultured epidermal, cell
      suspensions derived from neonatal skins of C57BL/10JHir (black) and its congenic
      mice carrying agouti, brown, albino, dilute, and pink-eyed dilution genes in a
      serum-free medium supplemented with dibutyryl adenosine 3',5'-cyclic
      monophosphate. The proliferative rates of agouti, brown and dilute black
      melanocytes were similar to that of black melanocytes, while those of albino and
      pink-eyed black melanocytes were about one-half of that of black melanocytes. The
      morphology of albino and pink-eyed black melanocytes, though nonpigmented, was
      similar to black melanocytes; namely, dendritic, polygonal or epithelioid. Dilute
      black melanocytes also possessed the similar morphology, whereas their
      melanosomes were accumulated in the perinuclear region. Dopa-melanin depositions
      after dopa reaction in brown and dilute black melanocytes were greater than in
      black and agouti melanocytes. Although dopa-melanin depositions were not observed
      in albino melanocytes, about 8% of pink-eyed black melanocytes were positive to
      dopa reaction. Silver depositions after combined dopa-premelanin reaction in
      agouti, brown and dilute black melanocytes were similar to that in black
      melanocytes. Although albino melanocytes were devoid of silver depositions, about
      25% of pink-eyed black melanocytes were positive to the reaction. Pyrrole-2,3,5
      tricarboxylic acid (PTCA, degradation product of eumelanin) contents in agouti
      and dilute black melanocytes were slightly lower than in black melanocytes, while
      that in brown melanocytes was reduced to one-third. In contrast, PTCA contents in
      albino and pink-eyed black melanocytes were reduced to less than 0.5%.
      Aminohydroxyphenylalanine (AHP, degradation product of pheomelanin) contents did
      not differ among these melanocytes. These results suggest that the coat-color
      genes exert their influences on the proliferation and differentiation of mouse
      epidermal melanocytes by affecting tyrosinase activity, melanosome maturation and
      transport, and eumelanin synthesis.

PMID- 9548376
TI  - A novel methodology for the investigation of intracellular proteolytic processing
      in intact cells.
AB  - Taking advantage of the unique spectral properties of the fluorescent probe FL
      Bodipy, we have developed a new methodology to study processing of exogenous
      proteins in intact cells. FL-Bodipy was conjugated to bovine serum albumin (BSA)
      at a molar ratio of 29 probe molecules to 1 albumin equivalent. The resulting
      conjugate was 98% self-quenched due to fluorescence resonance energy transfer
      (homotransfer) between neighboring Bodipy molecules. In vitro proteolytic
      cleavage of the conjugate led to relaxation of self-quenching and to a
      significant increase in fluorescence. Flow cytometry and fluorescence microscopy
      indicated that Bodipy-labeled BSA was readily internalized by J774 macrophages
      and accumulated in intracellular compartments. The kinetics of intracellular
      degradation of Bodipy-BSA was linear for up to 2 hours and was completely
      inhibited by a combination of protease inhibitors. Future applications of the
      methodology reported here may comprise studies of antigen processing and
      presentation, as well as the investigation of cellular events related to
      processing and disassembly of intracellular pathogens such as parasites, bacteria
      and viruses.

PMID- 9548377
TI  - Population heterogeneity of higher-plant mitochondria in structure and function.
AB  - Mitochondria of rapidly developing mungbean seedlings were fractionated into four
      populations: two density classes, each from a 1500S and a 150S pellet. Each of
      the four populations exhibited cytochrome c oxidase (COX) activity and contained
      mitochondrial DNA and cardiolipin; plastid and glyoxysome content were found to
      be relatively low. Five mitochondrial membrane proteins, COXII/III, ATPase
      alpha/beta and porin, and a matrix enzyme, manganese superoxide dismutase
      (MnSOD), were detected by immunoblots in all four populations. Another matrix
      enzyme, pyruvate dehydrogenase was detected only in the two respiratory-competent
      1500S populations. The two 150S populations contained a previously unidentified
      organelle that lacked demonstrable respiratory capability. This organelle, which
      we have tentatively referred to as "slow-sedimenting (ss-) mitochondrion", was
      small in size (below light-optics resolution, 70-300nm, majority < or =200nm) and
      possessed a peculiar looking boundary membrane, ribosomes, and an occasional
      prominent electron-dense spot. Characteristically, ss-mitochondria were almost
      always in contact with a filament-aligned membrane-like structure of varying
      length. Cristae structure, while undetected in small ss-mitochondria, appeared in
      larger individuals. Typical mitochondria were found in the denser 1500S
      population, while the lighter 1500S population consisted of 300-800 nm
      mitochondria exhibiting a varying degree of size-dependent inner membrane
      folding. Using electron microscopy (EM) immunolocalization and serial sectioning,
      we have identified in situ organelles resembling in size and in fine structure
      the ss-mitochondria, which also exhibit a size-dependent folding of the inner
      membrane. These results suggest that small ss-mitochondria may undergo a
      progressive development in situ. Taken together, our findings demonstrate the
      existence of a pattern of structure-function-coordinated gross heterogeneity
      among mitochondria. This pattern of mitochondrial heterogeneity, characterized
      both in isolated mitochondria and in situ, implies that small ss-mitochondria may
      represent a type of "nascent mitochondria" derived from a yet unidentified
      mitochondria-propagation mode operating during rapid seedling growth.
      Mitochondrial division by binary fission, characterized by the appearance of
      dumbbell-shaped intermediates, was also detected.

PMID- 9548378
TI  - Apomorphine-induced hypoattention in rats and reversal of the choice performance
      impairment by aniracetam.
AB  - Aging-, disease- and medication-related imbalance of central dopaminergic neurons
      causes functional impairment of cognition and neuropsychological delirium in
      humans. We attempted to develop a new delirium model using the direct dopamine
      agonist, apomorphine, and a choice reaction performance task performed by middle
      aged rats. The psychological properties of the model were assessed by determining
      behavioral measures such as choice reaction time, % correct and % omission.
      Apomorphine (0.03-0.3 mg/kg s.c.) produced a dose-dependent impairment of task
      performance. The dose of 0.1 mg/kg prolonged choice reaction time, decreased %
      correct and increased % omission, indicating that rats had attentional deficits
      and a reduced arousal or vigilance but no motor deficits or reduced food
      motivation. This psychological and behavioral impairment of performance resembled
      that of clinically defined delirium. In this model, the cholinomimetic,
      aniracetam (10 mg/kg p.o.), reversed the performance impairment induced by
      apomorphine. Its two metabolites, 2-pyrrolidinone (10 and 30 mg/kg p.o.) and N
      anisoyl-gamma-aminobutyric acid (GABA, 10 mg/kg p.o.), effectively reversed the
      performance impairment as the intact drug did. Another pyrrolidinone derivative,
      nefiracetam (10 and 30 mg/kg p.o.), tended to worsen the apomorphine effect. The
      cholinesterase inhibitor, tacrine (10 mg/kg p.o.), markedly worsened all of the
      behavioral measures. Neuroleptics, haloperidol (0.025 mg/kg s.c.), tiapride (30
      mg/kg p.o.) and sulpiride (10 and 30 mg/kg p.o.), antagonized the apomorphine
      effect. The present results suggest that apomorphine-induced behavioral
      disturbances in the choice reaction performance task seems to be a useful
      delirium model and aniracetam may improve delirium through the action of 2
      pyrrolidinone and N-anisoyl-GABA, presumably by facilitating dopamine release in
      the striatum by acting as an AMPA or metabotropic glutamate receptor agonist.

PMID- 9548379
TI  - Benzodiazepine receptor antagonists modulate the actions of ethanol in alcohol
      preferring and -nonpreferring rats.
AB  - The pyrazoloquinoline CGS 8216 (2-phenylpyrazolo-[4,3-c]-quinolin-3 (5H)-one,
      0.05-2 mg/kg) and the beta-carboline ZK 93426 (ethyl-5-isopropyl-4-methyl-beta
      carboline-3-carboxylate, 1-10 mg/kg) benzodiazepine receptor antagonists were
      evaluated for their capacity to modulate the behavioral actions of ethanol in
      alcohol preferring and -nonpreferring rats. When alcohol-preferring rats were
      presented with a two-bottle choice test between ethanol (10% v/v) and a saccharin
      (0.0125% g/v) solution, both antagonists dose-dependently reduced intake of
      ethanol by 35-92% of control levels on day 1 at the initial 15 min interval of
      the 4 h limited access. Saccharin drinking was suppressed only with the highest
      doses. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg) unmasked the anxiolytic
      effects of a hypnotic ethanol dose (1.5 g/kg ethanol) on the plus maze test in
      alcohol-preferring rats, but potentiated the ethanol-induced suppression in
      alcohol-nonpreferring rats. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg)
      attenuated the ethanol (0.5 and 1.5 g/kg)-induced suppression in the open field
      in alcohol-nonpreferring rats; however, CGS 8216 potentiated the depressant
      effects of the lower ethanol dose (0.5 g/kg) in alcohol-preferring rats. These
      findings provide evidence that benzodiazepine receptor antagonists may
      differentially modulate the behavioral actions of ethanol in alcohol-preferring
      and-nonpreferring rats. It is possible that the qualitative pharmacodynamic
      differences seen in the present study may be related to selective breeding for
      alcohol preference. The findings indicate the potential for development of
      receptor specific ligands devoid of toxic effects which may be useful in the
      treatment of alcohol abuse and alcoholism.

PMID- 9548381
TI  - The antidepressant, nefazodone, attenuates corticosterone-induced increases in 5
      HT2A receptor-mediated behaviors in the female rat.
AB  - The effects of chronic corticosterone administration on sexual behavior and on
      wet-dog shakes, a 5-HT2A mediated behavior, were investigated in the female rat.
      In addition, effects of the antidepressant nefazodone, a selective 5-HT2A
      receptor antagonist, both alone and in combination with corticosterone were
      examined. Testing was conducted in ovariectomized animals primed with estrogen
      and progesterone. Corticosterone was found to significantly increase sexual
      receptivity, sexual proceptivity and wet dog shakes. While nefazodone alone had
      no significant effects, it completely attenuated the corticosterone-induced
      increases in both sexual behavior and wet dog shakes. This suggests that
      corticosterone influences sexual behavior and wet dog shakes via a 5-HT2A
      receptor mechanism.

PMID- 9548380
TI  - Behavioral and neurochemical effects of the preferential dopamine D3 receptor
      agonist cis-8-OH-PBZI.
AB  - In the present study we investigated the in vivo pharmacological profile of the
      benz[e]indole cis-8-hydroxy-3-(n-propyl)],2,3a,4,5,9b-hexahydro-1H-benz[e]indole
      (cis-8-OH-PBZI), which has been described as a preferential dopamine D3 receptor
      agonist in vitro. The compound inhibited spontaneous locomotor activity in mice,
      an effect which was antagonized by the dopamine D3 receptor antagonist 5,6
      dimethoxy-2-(di-u-propylamino) indan (U99194A). Moreover, cis-8-OH-PBZI inhibited
      conditioned avoidance responding in rats, a preclinical test indicative of
      antipsychotic efficacy, at doses which did not induce catalepsy. Doses of cis-8
      OH-PBZI (6 and 12 mg/kg) that inhibited spontaneous locomotor activity in rats
      did not affect interstitial levels of dopamine and dihydroxyphenylacetic acid
      (DOPAC) in the nucleus accumbens or dorsolateral striatum. In contrast to the
      effect of the dopamine receptor agonist (+/-)-2-dipropylamino-7-hydroxy-1,2,3,4
      tetrahydronaphythalene (7-OH-DPAT), cis-8-OH-PBZI did not induce locomotor
      activity in reserpinized mice. In conclusion, cis-8-OH-PBZI exhibits a
      pharmacological profile that suggests it has antipsychotic activity but lacks the
      motoric side effects often associated with antipsychotic medication. The data
      suggest a mechanism requiring the activation of postsynaptic dopamine D3
      receptors and support the hypothesis that these receptors mediate inhibitory
      behavioral effects.

PMID- 9548382
TI  - Concentration-dependent actions of a new indene derivative, TN-871, in the
      enteric nervous system.
AB  - Intracellular electrical recordings and fluorimetric measurement of intracellular
      Ca2+ concentration ([Ca2+]i) were made from enteric neurons of the guinea-pig
      myenteric and submucosal plexuses to examine the actions of 2-n-butyl-1-(4
      methylpiperazinyl)5,6-ethylendioxyindene x 2HCl (TN-871) on neural activity in
      the single cell. TN-871 affected neuronal electrophysiological properties and
      synaptic transmission in the enteric nervous system in a concentration-dependent
      manner; TN-871 at lower concentrations hyperpolarized enteric neurons and/or
      facilitated synaptic transmission, whereas at higher concentrations it
      depolarized enteric neurons and/or inhibited synaptic transmission. Experiments
      with fura-2 showed that TN-871 modulated both resting [Ca2+]i and [Ca2+]i
      transient associated with action potentials. Thus, the present results
      demonstrated that TN-871 at lower concentrations facilitates but at higher
      concentrations depresses Ca2+-dependent or Ca2+-involving processes, suggesting
      that TN-871 may affect the Ca2+ dynamics in enteric neurons either directly,
      indirectly or both.

PMID- 9548383
TI  - Anxiolytic effects of flesinoxan in the stress-induced hyperthermia paradigm in
      singly-housed mice are 5-HT1A receptor mediated.
AB  - In the stress-induced hyperthermia paradigm in singly-housed male mice, two
      sequential rectal temperature measurements reveal the basal temperature (T1) and,
      10 min later, an enhanced body temperature (T2), due to the stress of the first
      rectal measurement. The difference T2 - T1 (deltaT) is the stress-induced
      hyperthermia and putatively reflects a stress-induced anxiogenic response. The
      full 5-HT1A receptor agonist flesinoxan ((+)-enantiomer), its (-)-enantiomer and
      the racemic mixture reduced stress-induced hyperthermia effects, indicating
      putative anxiolytic properties. The ratio of their potencies to reduce stress
      induced hyperthermia was similar to their potency in receptor binding affinities
      for 5-HT1A receptors, supporting that the anti-hyperthermia effects are mediated
      by the 5-HT1A receptor. This was further substantiated when the 5-HT1A receptor
      antagonists WAY 100635 ((N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl) cyclo-hexane carboxamine trihydrochloride) and DU 125530 (2-[4-[4-(7
      chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl ]butyl]-1,2-benzisothiazol
      3(2H)-one-1,1-dioxide, monomesylate) both were able to antagonize the anti-stress
      induced hyperthermia effects of flesinoxan. The stress-induced hyperthermia
      paradigm in singly-housed mice represents a simple and robust paradigm to measure
      putative anxiolytic effects of drugs.

PMID- 9548384
TI  - Inhibition of stimulus-triggered and spontaneous epileptiform activity in rat
      hippocampal slices by the Aconitum alkaloid mesaconitine.
AB  - The aim of the present study was to investigate if the plant alkaloid,
      mesaconitine, which has been reported to have antinociceptive effects via
      stimulation of the noradrenergic system, inhibits epileptiform field potentials.
      The experiments were performed as extracellular recordings on rat hippocampal
      slices. Epileptiform activity was induced by omission of Mg2+ from the bathing
      medium or by addition of bicuculline and stimulus-evoked population bursts were
      recorded in the CA1 region. Spontaneous epileptiform activity was elicited by
      perfusing a nominally Mg2+-free bathing medium with high K+ concentration (5 mM).
      Both stimulus-triggered and spontaneous epileptiform activity was attenuated in a
      concentration-dependent manner by mesaconitine (30 nM-1 microM). The inhibitory
      effect was rather variable in appearance when lower concentrations (30 and 100
      nM) of mesaconitine were applied. Pretreatment of the slices with the alpha
      adrenoceptor antagonist yohimbine (1 microM) prevented the effect of
      mesaconitine. It is concluded that the inhibitory action of mesaconitine at low
      concentration is mediated via alpha-adrenoceptors.

PMID- 9548385
TI  - Lubeluzole protects hippocampal neurons from excitotoxicity in vitro and reduces
      brain damage caused by ischemia.
AB  - Previously reported effects of lubeluzole, such as inhibition of glutamate
      release, inhibition of nitric oxide (NO) synthesis and blockage of voltage-gated
      Na+- and Ca2+-ion channels, suggest a neuroprotective action of this drug. Here
      we report about the effects of lubeluzole and its R-isomer on glutamate-induced
      neuronal cell death in mixed hippocampal cultures. In addition, we studied the
      effect of lubeluzole in focal cerebral ischemia models in mice and rats. In
      hippocampal cultures exposed to 500 nM glutamate for 1 h, lubeluzole (0.1-100
      nM), but not the R-isomer (1-100 nM), reduced the percentage of damaged neurons
      from 42 +/- 8% to 18 +/- 7% (P < 0.01). In mice and rats, lubeluzole reduced
      ischemic brain damage, when administered immediately after middle cerebral artery
      occlusion. Interestingly, the protective effect (reduction of the infarct volume
      in rats to 77% of control; P < 0.01) was also found when the lubeluzole treatment
      (2.5 mg/kg) was started 3 h after ischemia. Especially this latter effect
      suggests that lubeluzole will be a useful drug for stroke therapy.

PMID- 9548386
TI  - The potency of the novel tachykinin receptor antagonist CGP49823 at rat and
      gerbil motoneurones in vitro.
AB  - The novel tachykinin receptor antagonist CGP49823 ((2R,4S)-2-benzyl-1-(3,5
      dimethylbenzoyl)-4-(quinolin-4-y lmethylamino)piperidine) has been compared with
      three other selective non-peptide tachykinin NK1 receptor antagonists. The drugs
      were tested as antagonists of the depolarization of spinal motoneurones induced
      by bath application of the selective tachykinin NK1 receptor agonist septide-(6
      11) (300 nM) for 120 s at 15 min intervals. The antagonists were bath applied and
      the depolarizations were recorded from lumbar ventral roots of 7 to 12 day old
      rat and gerbil hemisected spinal cords in vitro. The gerbil preparation is
      considered to model the human species variant of the tachykinin NK1 receptor.
      With the exception of SR140333 ((S)-1-[2-[3-(3,4-dichlorophenyl)-1-[[3-(1
      methylethoxy)phenyl]ace tyl]-3-piperidinyl]ethyl]-4-phenyl-1
      azoniabicyclo[2.2.2]octane chloride), the antagonists were approximately thirty
      fold more potent on gerbil preparations. The respective mean IC50 values from
      gerbil preparations produced by CP96345 ((2S-cis)-2-(diphenylmethyl)-N-[(2
      methoxyphenyl)methyl]-1-azabicy clo[2.2.2]octan-3-amine), CGP49823, SR140333 and
      CP99994 ((2S-cis)-N-[(2-methoxyphenyl)methyl]-2-phenyl-3-piperidinamine) were, in
      microM +/- S.E. (n) 0.10 +/- 0.02 (6), 0.22 +/- 0.03 (6), 0.30 +/- 0.10 (5) and
      0.38 +/- 0.02 (5) and the corresponding values from the rat preparations were 3.7
      +/- 0.4 (5), 7.8 + 1.3 (5), 1.06 +/- 0.16 (6) and 10.5 +/- 2.2 (7). Dominance of
      tachykinin NK1 receptor activity in the measured responses was confirmed by low
      potency of the tachykinin NK2-selective antagonist SR48968 ((S)-N-methyl-N[4-(4
      acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl] benzamide) which
      yielded an IC50 value of 12.0 +/- 2.8 (5) on gerbil preparations and produced
      less than 50% depression of septide-induced depolarization of rat motoneurones at
      the highest concentration (100 microM) tested.

PMID- 9548388
TI  - Arachidonic acid metabolites and the synaptic potentiation evoked by activation
      of metabotropic glutamate receptors.
AB  - We have previously shown that coapplication of arachidonic acid (10 microM) and
      (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 50 microM) evokes an
      enhancement of synaptic transmission in the CA1 region of the rat hippocampal
      slice. Here we have investigated whether the metabolites of arachidonic acid are
      implicated in this potentiation. Inclusion of the cyclo-oxygenase inhibitor
      indomethacin (10 microM) did not block the potentiation induced by coapplication
      of arachidonic acid and ACPD. However, the presence of either the cyclo-, lipo-
      and epoxygenase inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA, 20 microM), or
      the lipoxygenase inhibitor nordihydroguaiaretic acid (10 microM), prevented the
      long-lasting enhancement. The results suggest that the lipoxygenase and
      epoxygenase metabolites of arachidonic acid may be involved in the induction of
      this form of synaptic potentiation.

PMID- 9548387
TI  - MK-801 reverses Fos expression induced by the full dopamine D1 receptor agonist
      SKF-82958 in the rat striatum.
AB  - Administration of the selective and full dopamine D1 receptor agonist SKF-82958
      ((+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-b
      enzazepine) (1 and 3 mg/kg i.p.) led to a dose-dependent induction of Fos protein
      in the rat striatum. The 3 mg/kg SKF-82958-induced expression of striatal Fos
      protein was blocked by the dopamine D1 receptor antagonist SCH-23390 (R(+)-7
      chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine) (0.3
      mg/kg i.p.). The noncompetitive NMDA receptor antagonist MK-801 ((5R,10S)-(+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5 ,10-imine) (1 mg/kg i.p.) also
      completely prevented striatal Fos induction by an injection of 3 mg/kg SKF-82958.
      These results suggest that dopamine D1 receptor activation by the full agonist
      SKF-82958 is sufficient to trigger Fos expression in the striatum, but that
      concomitant stimulation of NMDA receptors is required for the striatal Fos
      induction in response to dopamine D1 receptor activation.

PMID- 9548389
TI  - Halothane attenuates nitric oxide relaxation of rat aortas by competition for the
      nitric oxide receptor site on soluble guanylyl cyclase.
AB  - Endothelial cells play an important role in the regulation of vascular activity
      through the release of endothelium derived relaxing factor (EDRF) now believed to
      be nitric oxide (NO). NO and the NO donor drug nitroglycerin relax vascular
      smooth muscle by stimulating soluble guanylyl cyclase leading to elevation of
      intracellular levels of cyclic guanosine 3',5'-monophosphate (cGMP). Halothane
      has been shown to inhibit the action of NO on blood vessels. This study was
      designed to further investigate the mechanisms by which halothane attenuates NO
      induced vascular relaxations. This was done by examining the effects of halothane
      on nitroglycerin and NO-induced relaxations in the presence and absence of the
      inhibitors of soluble guanylyl cyclase, methylene blue and 6-anilino-5,8
      quinolinedione (LY 83583). Thoracic aortas from anesthetized male Sprague-Dawley
      rats were excised and cut into rings and the endothelium was removed. The aortic
      rings were suspended in organ baths containing Krebs solution and equilibrated at
      their optimal passive tension. When a stable plateau of contraction was produced
      by EC60 concentrations of norepinephrine, increasing concentrations of
      nitroglycerin or NO were added to the baths to relax the rings. This contraction
      relaxation procedure was repeated three or four times. In some baths halothane
      was administered by a calibrated vaporizer 10 min before beginning the second
      procedure. Either methylene blue or LY 83583 was added to the baths 20 min before
      the third procedure. The combination of halothane, methylene blue or LY 83583 was
      added before the fourth procedure. Halothane, methylene blue or LY 83583
      significantly inhibited nitroglycerin-induced relaxation individually. Halothane
      and LY 83583 also significantly inhibited NO-induced relaxations (5 x 10(-9)-3 x
      10(-8) M and 5 x 10(-9)-3 x 10(-5) M, respectively) individually. The combination
      of halothane and methylene blue or halothane and LY 83583 significantly inhibited
      nitroglycerin-induced relaxation, also, the combination of halothane and LY 83583
      significantly inhibited NO-induced relaxations. Halothane, methylene blue and LY
      83583 treatment led to rightward shift in the concentration-effect curves.
      Halothane, in combination with methylene blue or LY 83583, produced inhibition
      equivalent to the sum of their individual effects. The present study demonstrates
      that the halothane, methylene blue and LY 83583 attenuate nitroglycerin and NO
      induced relaxations of endothelium-denuded rat aortic rings. This suggests that
      halothane, methylene blue and LY 83583 may act through competitive antagonism at
      a common site of action on soluble guanylyl cyclase in the EDRF/NO relaxation
      pathway.

PMID- 9548390
TI  - Coronary vasoconstriction produced by vasopressin in anesthetized goats. Role of
      vasopressin V1 and V2 receptors and nitric oxide.
AB  - To examine the role of vasopressin V1 and V2 receptors, nitric oxide and
      prostanoids in the coronary vascular effects of [Arg8]vasopressin, coronary blood
      flow was measured with an electromagnetic flow transducer placed around the left
      circumflex (23 goats) or anterior descending (11 goats) coronary artery and
      vasopressin (0.03-1 microg) was intracoronarily injected in 34 anesthetized, open
      chest goats. Basal mean values for coronary blood flow, mean systemic arterial
      pressure and heart rate, were 34 +/- 2.38 ml/min, 89 +/- 3.34 mmHg and 80 +/-
      3.06 beats/min, respectively. Vasopressin produced dose-dependent decreases in
      coronary blood flow and the maximal reduction of this flow, attained with 1
      microg of vasopressin, was 14 +/- 1.49 ml/min (42 +/- 2.64% of basal flow) (P <
      0.01). Desmopressin (0.03-1 microg; 8 goats) did not affect significantly
      coronary blood flow. The intracoronary infusion of the antagonist for vasopressin
      V1 receptors d(CH2)5Tyr (Me) arginine vasopressin (2 microg/min per kg, 6
      animals) significantly diminished the effects of vasopressin on coronary blood
      flow (the effects of 1 microg of vasopressin were reduced by 28%, P < 0.05). The
      mixed antagonist for vasopressin V1 and V2 receptors desGly-d(CH2)5-D-Tyr(Et)Val
      arginine vasopressin (0.2, 0.7 and 2 microg/min per kg, 9 animals) decreased in a
      dose-dependent manner the effects of vasopressin on coronary blood flow (the
      effects of 1 microg of vasopressin were decreased by 61% with 2 microg/min per
      kg, P < 0.01). Intracoronary infusion of saline (vehicle, 3 goats) did not change
      the effects of vasopressin on coronary blood flow. Intravenous administration of
      the inhibitor of nitric oxide synthesis N-omega-nitro-L-arginine methyl ester (L
      NAME, 47 mg/kg, 9 animals) decreased resting coronary blood flow by 10% (P <
      0.01) and augmented mean systemic arterial pressure by 20% (P < 0.01), without
      changing heart rate. During this treatment the reduction in coronary blood flow
      produced by vasopressin was higher than under control (the effects of 1 microg of
      vasopressin were increased by 28%, P < 0.01). Intravenous administration of the
      inhibitor of cyclooxygenase, meclofenamate (5 mg/kg, 7 animals), neither modified
      resting coronary blood flow, arterial pressure and heart rate nor the effects of
      vasopressin on this flow. These data indicate that vasopressin produces marked
      coronary vasoconstriction and suggest that: (a) it may be mediated by vasopressin
      V1 receptors, without involvement of vasopressin V2 receptors, (b) it is probably
      inhibited by nitric oxide under normal conditions and (c) it may be not modulated
      by prostanoids.

PMID- 9548391
TI  - The effect of chronic L-carnitine treatment on blood pressure and plasma lipids
      in spontaneously hypertensive rats.
AB  - The effect of chronic L-carnitine treatment on blood pressure and plasma lipids
      was studied in spontaneously hypertensive rats (SHR). L-Carnitine treatment for 6
      weeks lowered significantly both the systolic and mean arterial pressure of SHR
      but its influence on diastolic and pulse pressure was only modest. L-Carnitine
      did not influence the relative heart and kidney weight of SHR. However, L
      carnitine completely abolished the age-dependent rise of plasma total
      cholesterol, triglycerides and uric acid seen in untreated SHR. On the other
      hand, L-carnitine treatment had no significant effects on blood pressure,
      relative organ weight and plasma lipids in normotensive Wistar-Kyoto rats. Our
      results suggest that L-carnitine might prevent some cardiovascular alterations by
      its influence on lipid metabolism.

PMID- 9548393
TI  - Central effect of SNC 80, a selective and systemically active delta-opioid
      receptor agonist, on gastrointestinal propulsion in the mouse.
AB  - We investigated the effects of SNC 80 ((+)-4-[alphaR)-alpha-((2S,5R)-4-ally1-2,5
      dimethyl-1-pipera zinyl)-3-methoxybenzyl]-N,N-diethylbenzamide), a new highly
      selective, non-peptidic and systemically active delta-opioid receptor agonist, on
      gastrointestinal and colonic propulsion in mice. Intraperitoneally (i.p.) SNC 80
      (1, 10 and 30 mg/kg) significantly decreased gastrointestinal propulsion measured
      as transit of an orally administered charcoal meal. Pretreatment with the delta
      opioid receptor antagonist, naltrindole (1 mg/kg) subcutaneously (s.c.), with the
      non-selective opioid antagonist, naloxone (5 mg/kg, s.c.) or the mu1-opioid
      receptor antagonist, naloxonazine (10 mg/kg, i.p.), significantly decreased the
      antitransit effect of SNC 80 but pretreatment with the non-selective opioid
      antagonist, naloxone methiodide (5 mg/kg, s.c.), a quaternary salt of naloxone
      that does not cross the blood-brain barrier, did not. SNC 80 (1, 5 and 10 mg/kg,
      i.p.), produced dose-related inhibition of colonic propulsion measured as the
      increase in mean expulsion time of a 3 mm glass bead placed in the distal colon.
      Naloxone (5 mg/kg, s.c.) and naltrindole (1 mg/kg, s.c.), completely antagonized
      the colonic antipropulsive effect of SNC 80. In contrast, naloxone methiodide (5
      mg/kg, s.c.), left the inhibitory effect of i.p. SNC 80 on colonic function
      unchanged. These results suggest that peripherally injected SNC 80 inhibits
      gastrointestinal transit and colonic propulsion. It does so mainly through a
      central mechanism. Although the gastrointestinal antitransit effect of SNC 80 is
      naltrindole- and naloxonazine-sensitive, we cannot exclude an opioid-independent
      mechanism. The colonic antipropulsive effect of SNC 80 confirms the inhibitory
      role of the central delta-opioid receptor system on colonic motility.

PMID- 9548392
TI  - Platelet-activating factor receptor antagonist attenuates endotoxin-induced
      vascular hyporeactivity in the pithed rat.
AB  - The role of platelet activating factor (PAF) and nitric oxide (NO) in the
      endotoxin-induced hyporeactivity to noradrenaline was studied in the pithed rat.
      Pressor dose-response curves to noradrenaline (0.01-10 microg/kg, i.v.) were made
      starting 1 h after the administration of endotoxin (0.5 mg/kg, i.v.) to the rats.
      Saline was administered to the control rats. The PAF receptor antagonist, TCV-309
      (3-bromo-5-[N-phenyl-N-[2-[[2-(1,2,3,4-tetrahydro-2-isoquinolylcarbon
      yloxy)ethyl]carbamoyl]ethy]carbamoyl]-1-propylpyridinium nitrate, 100 microg/kg,
      i.v.), or the NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA, 30
      mg/kg, i.v.), was administered to the endotoxin-treated rats 20 or 10 min before
      the noradrenaline challenge. L-NMMA reversed endotoxin-induced hyporeactivity
      completely. TCV-309 produced a significant, but partial attenuation of the
      hyporeactivity to noradrenaline (P < 0.01). There was still significant
      hyporeactivity when compared with the control rats (P < 0.01) and the L-NMMA
      treated endotoxin-administered rats (P < 0.05). These data suggest that
      endogenous PAF contributes to the vascular hyporeactivity to noradrenaline
      induced by endotoxin and that NO plays a major role in the endotoxin-induced
      hyporeactivity.

PMID- 9548395
TI  - Respiratory effects of halothane and AMPA receptor antagonist synergy in rats.
AB  - The influence of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA) receptor antagonists in combination with
      halothane anaesthesia on the respiratory system was investigated. Under 1.5%
      halothane anaesthesia, respiratory parameters including respiratory rate, minute
      volume, tidal volume, inspiratory and expiratory duration were measured before
      and after drug administration in rats. The AMPA receptor antagonists, 6-(1H
      imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride, YM90K (5 and
      10 mg/kg) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX, 15
      mg/kg), which were administered intravenously for 30 min, significantly reduced
      the respiratory rate (P < 0.01) and minute volume (P < 0.01) and increased the
      tidal volume (P < 0.05) compared with values obtained before drug administration.
      None of these drugs affected respiratory parameters in the absence of
      anaesthesia. A NMDA receptor antagonist, MK-801 (0.5 mg/kg), which was
      administered intravenously for 30 min, also significantly reduced respiratory
      rate (P < 0.01), minute volume (P < 0.01) and tidal volume (P < 0.01) and
      prolonged inspiratory duration (P < 0.05). These results suggest that both AMPA
      and NMDA receptor antagonists cause respiratory depression under halothane
      anaesthesia in rats, although the mechanisms may be different for the two types
      of antagonists.

PMID- 9548394
TI  - Effect of cigarette smoke on ethanol-induced gastric mucosal lesions: the role of
      nitric oxide and neutrophils.
AB  - The roles of neutrophil aggregation, inducible nitric oxide synthase activation
      and chemoattractant, leukotriene B4, in potentiation of the cigarette smoke
      effect on ethanol-induced gastric mucosal damage were studied. Smoke exposure
      markedly increased gastric lesion formation following ethanol administration and
      this was accompanied by substantial increase in gastric mucosal leukotriene B4
      concentration, myeloperoxidase and inducible nitric oxide synthase activities.
      Antineutrophil serum or aminoguanidine pretreatment significantly attenuated both
      gastric mucosal lesion formation and inducible nitric oxide synthase activity.
      The increased myeloperoxidase activity was abolished by antineutrophil serum but
      not by aminoguanidine. These data indicated that both neutrophil mobilization and
      inducible nitric oxide synthase activation in the gastric mucosa play an
      important role in the potentiating action of cigarette smoke on ethanol-induced
      gastric mucosal lesion formation. Increased synthesis of nitric oxide from
      inducible nitric oxide synthase during gastric damage may be secondary to
      neutrophil infiltration in the gastric mucosa. Chemoattractant leukotriene B4
      could also contribute to neutrophil recruitment in the tissue.

PMID- 9548396
TI  - Preventive effects of the deleted form of hepatocyte growth factor against
      various liver injuries.
AB  - The effects of a naturally occurring deleted form of hepatocyte growth factor
      (HGF) on hepatic disorder were studied in various models of hepatic failure. The
      pretreatment of rats and mice with the deleted form of HGF prevented the liver
      injuries and coagulopathy induced by endotoxin, dimethylnitrosamine and
      acetaminophen and reduced the mortality due to hepatic dysfunction induced by
      these hepatotoxins. The concurrent administration of the deleted form of HGF also
      prevented the liver injury and hepatic fibrosis in mice treated with alpha
      naphthylisothiocyanate and in rats treated with dimethylnitrosamine. Moreover,
      the deleted form of HGF normalized the results of the bromosulphalein-clearance
      test and ameliorated jaundice in rats with periportal cholangiolitic hepatopathy
      induced by alpha-naphthylisothiocyanate. The deleted form of HGF also reversed
      the coagulopathy in rats with hepatic disorder induced by dimethylnitrosamine or
      by 70% resection of cirrhotic liver (induced by carbon tetrachloride). In Long
      Evans cinnamon rats receiving vehicle, 20 out of 21 animals died within 4 days
      after the onset of jaundice. After infusion of the deleted form of HGF for 4
      days, 7 out of 20 Long-Evans cinnamon rats survived. These results indicate that
      the deleted form of HGF could have therapeutic potency in patients with severe
      hepatic failure.

PMID- 9548398
TI  - A nitric oxide donor NOC 7 suppresses renal responses induced by norepinephrine
      and angiotensin II in the NO-depleted denevated rabbit kidney.
AB  - Intrarenal arterial infusion of norepinephrine (30 ng/kg per min) or of
      angiotensin II (4 ng/kg per min) reduced the glomerular filtration rate and
      urinary Na+ excretion in denervated kidneys of anesthetized rabbits pretreated
      intrarenally with a nitric oxide (NO) synthase inhibitor N(omega)-nitro-L
      arginine methyl ester (50 microg/kg per min). Angiotensin II but not
      norepinephrine reduced fractional Na+ excretion. Intrarenal administration of a
      spontaneous NO donor 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1
      triazene (NOC 7, 30 ng/kg per min) in L-NAME pretreated kidneys did not affect
      basal values, but attenuated the reduction in urinary Na+ excretion induced by
      these agonists without affecting the angiotensin II-induced reduction in
      glomerular filtration rate. The results suggest that NOC 7 can suppress the
      norepinephrine-induced hypofiltration and the angiotensin II-evoked tubular
      reabsorption and thereby attenuates the agonist-induced antinatriuresis in the
      denervated and endogenous NO-depleted rabbit kidney.

PMID- 9548397
TI  - Effect of dopamine on NaCl transport in the medullary thick ascending limb of the
      rat.
AB  - The aim of the present study was to determine whether dopamine affects NaCl
      reabsorption in the medullary thick ascending limb of the loop of Henle.
      Basolateral dopamine (10(-6) M) significantly inhibited Cl- reabsorption in the
      in vitro microperfused rat medullary thick ascending limb by 21 +/- 2% (P <
      0.01). The response to 10(-6) M dopamine was completely blocked by pretreatment
      with the dopamine D1 receptor antagonist R(+)-SCH-23390 (5 x 10(-5) M), and was
      mimicked by the dopamine D1 receptor agonist A-77636 (10(-6) M; delta - 36 +/-
      2%; P < 0.05). In contrast, basolateral administration of the dopamine D2
      receptor agonist (+)-bromocriptine (10(-6) M) transiently increased Cl-
      reabsorption by 49 +/- 18% (P < 0.05). Neither the D1 nor the D2 agonist affected
      Cl- reabsorption when selectively administered to the luminal membrane. These
      data suggest that the predominant effect of dopamine on the medullary thick
      ascending limb of the rat is to inhibit the reabsorption of NaCl, a response
      which is mediated by dopamine D1 receptors.

PMID- 9548399
TI  - Insulin and glucagon secretion by ganglionic nicotinic activation in
      adrenalectomized mice.
AB  - The pancreatic islets are innervated by nerves emanating from intra- and
      extrapancreatic ganglia. However, the effects of ganglionic activation on insulin
      and glucagon release in vivo have not been established. We therefore investigated
      the effects of pharmacological ganglionic activation by the nicotinic agonists
      DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) and nicotine on insulin and
      glucagon release in sham-operated and adrenalectomized mice. In sham-operated
      animals, DMPP (0.5 or 1.6 micromol/kg, i.v.) or nicotine (0.075 or 0.75
      micromol/kg, i.v.), did not affect plasma insulin levels, but markedly increased
      plasma glucagon levels (P < 0.05). In contrast, after adrenalectomy or alpha2
      adrenoceptor blockade by yohimbine (3.6 micromol/kg), nicotinic activation
      markedly increased plasma insulin levels (P < 0.05), whereas the glucagon
      response to nicotinic activation was inhibited under these conditions (P < 0.05).
      We conclude that pharmacological ganglionic nicotinic activation in mice
      stimulates insulin and glucagon secretion. The insulinotropic effect is, however,
      counteracted by a concomitant adrenal activation through an alpha2-adrenoceptor
      mediated mechanism.

PMID- 9548400
TI  - Combination of OK432 and human interferon-alpha for treating viral-induced
      diabetes mellitus in mice.
AB  - We investigated the therapeutic effects of OK432 (picibanil; CAS39325-1-4), an
      immunomodulator that is derived from the Su strain of Streptococcus pyogenes.
      This agent was administered alone or combined with human interferon-alpha in a
      murine model of insulin-dependent diabetes mellitus. Interferon-alpha inhibits
      viral replication, reducing the incidence of virus-induced IDDM. Groups of DBA/2
      mice (N = 25 per group) received an intraperitoneal injection of OK432 and
      interferon-alpha daily for 16 d beginning 1 d after inoculation with 500 plaque
      forming units of encephalomyocarditis virus (EMCV). The dose of OK432 was one
      clinical unit (corresponding to 0.1 mg dried cells) per mouse, and that of
      interferon-alpha was 1 x 10(4) u/g. The animals were killed at random at 3 or 7 d
      after inoculation with EMCV. The survival rate of mice treated with the
      combination of OK432 and with interferon-alpha was significantly greater than
      that of the non-treated infected control animals (P < 0.01). Fasting levels of
      blood glucose were significantly lower in the mice administered the combination,
      than in the controls, both on day 3 (68 +/- 21 mg/dl vs. 270 +/- 135 mg/dl, P <
      0.01) and on day 7 (101 +/- 29 mg/dl vs. 219 +/- 112 mg/dl, P < 0.01). Serum
      levels of insulin were significantly higher in the treated mice than in the
      controls (65 +/- 5 vs. 55 +/- 1 microU/ml, P < 0.05). However, in the mice
      treated with OK432 or interferon-alpha alone, the survival rate and the blood
      level of glucose and insulin did not differ from those of infected controls.
      Natural killer (NK) cell activity was significantly higher in the mice treated
      with the drug combination than in the controls on both days evaluated: day 3, 65
      +/- 5 vs. 55 +/- 1%, n = 3, P < 0.05; day 7, 44 +/- 3 vs. 22 +/- 8%, n = 3, P <
      0.05). Serum levels of murine interferon in the treated mice exceeded those in
      controls on both days evaluated (day 3, 671 U/ml vs. 442 U/ml; day 7, 57 U/ml vs.
      43 U/ml). There were no significant differences in NK cell activity or in the
      interferon level in mice treated with either OK432 or interferon-alpha alone as
      compared with the infected, non-treated controls. Results suggest that the
      combination of OK432 and interferon-alpha protects against virally induced IDDM
      by increasing the activity of NK cells as well as the plasma level of interferon.

PMID- 9548402
TI  - Alpha1-adrenoceptor subtype activation increases proto-oncogene mRNA levels. Role
      of protein kinase C.
AB  - Noradrenaline increased the mRNA levels of c-fos and c-jun in rat-1 fibroblast
      lines stably expressing the cloned alpha1-adrenoceptor subtypes. The efficacy to
      induce the expression of c-fos mRNA was similar for the three cell lines (alpha1d
      = alpha1b = alpha1a) but different for c-jun (alpha1a > or = alpha1b > alpha1d).
      The EC50 values were also different: approximately 5 nM (c-fos) and approximately
      300 nM (c-jun) for cells transfected with the alpha1a subtype, approximately 30
      nM (c-fos) and approximately 300 nM (c-jun) for cells transfected with the
      alpha1b subtype and approximately 300 nM (c-fos and c-jun) for those transfected
      with the alpha1d subtype. Staurosporine and protein kinase C down-regulation
      blocked such effects, indicating a role of this protein kinase. Endothelin-1 (10
      nM) also increased the levels of c-fos and c-jun mRNAs. These actions of
      endothelin-1 were unaffected by staurosporine and protein kinase C down
      regulation. It is concluded that activation of any of the three cloned subtypes
      can increase the levels of c-fos and c-jun mRNAs and that protein kinase C plays
      a major role in mediating such effects.

PMID- 9548401
TI  - Glatiramer acetate blocks the activation of THP-1 cells by interferon-gamma.
AB  - Glatiramer acetate (previously known as copolymer 1) is a synthetic copolymer of
      four amino acids that has been approved for use in the treatment of multiple
      sclerosis. It has been shown to suppress myelin antigen specific T cell
      activation by competing with these antigens at the major histocompatibility
      complex class II binding site and by inducing antigen specific suppressor T
      cells. In this study we investigated the effects of glatiramer acetate on the
      human monocytic cell line, THP-1, activated by lipopolysaccharide and interferon
      gamma as a model for macrophages. At non-toxic concentrations of glatiramer
      acetate there were dose dependent reductions in the percentage of cells
      expressing human leukocyte DR and DQ antigen as well as in mean fluorescence
      intensity by flow cytometry. Production of tumor necrosis factor-alpha and the
      lysosomal cysteine proteinase cathepsin B were markedly inhibited, but production
      of interleukin-1 increased. These results suggest that glatiramer acetate might
      alter macrophage effector function and suggest that further studies in human
      monocytes and macrophages are warranted.

PMID- 9548403
TI  - Binding characterization of [3H]S-0139, an antagonist of the endothelin ET(A)
      receptor subtype.
AB  - S-0139 (27-O-3-[2-(3-carboxy-acryloylamino)-5-hydroxyphenyl]-acryloylo xy
      myricerone, sodium salt) is a highly specific nonpeptide endothelin ET(A)
      receptor antagonist. The binding of [3H]S-0139 was compared to that of
      [125I]endothelin-1 to characterize the binding of the antagonist in porcine
      aortic smooth muscle membranes. Scatchard analysis revealed a single class of
      [3H]S-0139 binding sites with a Kd value of 0.61 +/- 0.10 nM and a Bmax of 0.72
      +/- 0.16 pmol/mg protein. These sites were saturable and reversible.
      [125I]Endothelin-1 also showed binding with high affinity (Kd = 0.12 +/- 0.02 nM)
      to a homogeneous population of binding sites, whose Bmax (0.71 +/- 0.20 pmol/mg
      protein) was almost the same as that for [3H]S-0139. In both cases, the binding
      could be displaced by known endothelin receptor ligands and their IC50 values in
      each case showed a very close correlation (r = 0.986). The potency of seven
      endothelin receptor antagonists to displace [3H]S-0139 binding also correlated
      highly to the potency for inhibiting the endothelin-1-induced increase in
      cytosolic Ca2+ concentration (r = 0.949). Myriceric acid A showed a more potent
      functional activity than expected from its binding affinity, but this seemed to
      result from the different assay conditions, such as incubation time. Together,
      the results suggest that S-0139 labels only endothelin ET(A) receptor binding
      sites in porcine aortic smooth muscle.

PMID- 9548404
TI  - Mechanism of the dynorphin-induced dualistic effect on free intracellular Ca2+
      concentration in cultured rat spinal neurons.
AB  - In order to study the different mechanisms of dynorphin spinal analgesia and
      neurotoxicity at low and high doses, the effects of various concentrations of
      dynorphin A-(1-17) on the free intracellular Ca2+ concentration ([Ca2+]i) in the
      cultured rat spinal neurons were studied using single cell
      microspectrofluorimetry. While dynorphin A-(1-17) 0.1-100 microM had no
      significant effect on basal [Ca2+]i, dynorphin A-(1-17) 0.1 and 1 microM
      significantly decreased the high KCl-evoked peak [Ca2+]i by 94% and 83%
      respectively. Dynorphin A-(1-17) 10 and 100 microM did not affect the peak
      [Ca2+]i following K+ depolarization, but in all these neurons there was a
      sustained and irreversible rise in [Ca2+]i following high-K+ challenge.
      Pretreatment with the specific kappa-opioid receptor antagonist nor
      binaltorphimine 10 microM, but not the competitive NMDA receptor antagonist, DL-2
      amino-5-phosphonovalerate (APV) 10 microM, significantly blocked the inhibitory
      effect of dynorphin A-(1-17) 0.1 microM on peak [Ca2+]i. However, APV 10 microM
      and nor-binaltorphimine 10 microM significantly antagonized the sustained rise in
      [Ca2+]i induced by a high concentration of dynorphin A-(1-17) 10 microM.
      Furthermore, in the presence, and following the addition, of increasing
      concentrations of dynorphin A-(1-17) (0.1, 1, 10 and 100 microM), the high
      concentrations of dynorphin A-(1-17) failed to produce a sustained rise in peak
      [Ca2+]i. These results suggested that dynorphin exerted a dualistic modulatory
      effect on [Ca2+]i in cultured rat spinal neurons, inducing a sustained and
      irreversible intracellular Ca2+ overload via activation of both NMDA and kappa
      opioid receptors at higher concentrations, but inhibiting depolarization-evoked
      Ca2+ influx via kappa-opioid but not NMDA receptors at lower concentrations.
      Serial addition of graded concentrations of dynorphin A-(1-17) prevented the
      effect of high concentrations of dynorphin A-(1-17) on [Ca2+]i.

PMID- 9548405
TI  - Chloroquine inhibits alpha1B-adrenergic action in hepatocytes.
AB  - Noradrenaline increased phosphorylase a activity through activation of alpha1B
      adrenoceptors in rat hepatocytes. Such effect was inhibited by chloroquine (Ki
      approximately 55 nM) and only slightly reduced by high concentrations of
      primaquine. Chloroquine did not inhibit the activation of phosphorylase a induced
      by vasopressin or angiotensin II. Binding competition experiments using
      [3H]prazosin showed that both chloroquine and primaquine interact with alpha1B
      adrenoceptors, but only at very high concentrations. This indicates that the
      ability of chloroquine to block the alpha1B-adrenergic action was not due to
      antagonism at the receptor level. Noradrenaline increased phosphatidylinositol
      resynthesis and inositol trisphosphate production; these effects were inhibited
      by chloroquine and phorbol 12-myristate 13-acetate. Staurosporine and Ro 31-8220
      (3-[1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3 
      yl)maleimide), reduced the inhibitions induced by the active phorbol ester and
      the antimalarial drug on adrenergic-stimulated phosphatidylinositol resynthesis.
      Similarly, staurosporine blocked the inhibitory actions of chloroquine and
      phorbol 12-myristate 13-acetate on noradrenaline-stimulated inositol
      trisphosphate production. These data suggest the possibility that protein
      kinases, such as protein kinase C, could be involved in the actions of
      chloroquine.

PMID- 9548406
TI  - Different potencies of dihydropyridine derivatives in blocking T-type but not L
      type Ca2+ channels in neuroblastoma-glioma hybrid cells.
AB  - Evidence has accumulated that classic L-type Ca2+ channel blockers with a
      dihydropyridine structure also inhibit T-type Ca2+ channels in certain types of
      central and peripheral neurons and in smooth muscle cells, albeit with a lower
      potency. Thus beneficial therapeutic effects of dihydropyridines in
      cardiovascular and neurological diseases may not only be associated with L-type
      but also with T-type Ca2+ channel blockade. Little is known about the exact order
      of potency of dihydropyridine derivatives at T-type Ca2+ channels. Here we
      investigate the efficacy and potency of four therapeutically used compounds, i.e.
      nifedipine, nimodipine, nicardipine, niguldipine, in the neuroblastoma-glioma
      cell line NG108-15. For comparative purposes the Ca2+ channel agonist Bay K 8644
      was included. Ca2+ channel currents were measured with the whole-cell voltage
      clamp technique. Subtype Ca2+ channel currents were separated by clamp protocol
      and selective blockers. T-type Ca2+ channel currents were inhibited with
      decreasing potency in the order niguldipine > nicardipine > nimodipine >
      nifedipine (IC50-values 244 nM, 2.5 microM, 9.8 microM, 39 microM), whereas L
      type Ca2+ channel currents were blocked with similar potency (IC50 for
      nicardipine 75 nM). Bay K 8644 increased T-type Ca2+ channel current at nanomolar
      concentrations (i.e. 95 +/- 16% increase by 300 nM). T-type Ca2+ channel block
      was completely reversible with exception of the block by niguldipine. Our results
      indicate a variability of two orders of magnitude in potency of T-type Ca2+
      channel block by the dihydropyridine derivatives investigated. It is speculated
      that the relation between the L- and T-type Ca2+ channel block may determine the
      therapeutic profile of a dihydropyridine derivative.

PMID- 9548407
TI  - CP-060S interacts with three principal binding sites on the L-type Ca2+ channel.
AB  - CP-060S, (-)-(S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxypheny1]-3-[3-[N-met hyl-N
      [2-(3,4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thi azolidin-4-one hydrogen
      fumarate is a novel cardioprotective drug, which is able to prevent Na+-, Ca2+
      overload and also has Ca2+ channel blocking activity. The latter action of CP
      060S was characterized by radioligand binding experiments with rat cardiac
      membranes in terms of the interaction with the three principal binding sites on
      the L-type Ca2+ channel, which bind such drugs as the 1,4-dihydropyridines,
      phenylalkylamines and benzothiazepines. CP-060S exhibited complete and
      concentration-dependent inhibition of [3H](+)-PN200-110, [3H](-)
      desmethoxyverapamil and [3H]cis-(+)-diltiazem binding to their specific binding
      sites. Saturation studies showed that CP-060S increased the Kd of [3H](+)-PN200
      110 and [3H](-)-desmethoxyverapamil without causing a significant change in the
      maximum binding density. The dissociation kinetics of the three radioligands were
      accelerated by CP-060S. These results suggest that CP-060S interacts with a novel
      binding site on the L-type Ca2+ channel and has a negative allosteric interaction
      with the three principal binding sites for the 1,4-dihydropyridines,
      phenylalkylamines and benzothiazepines.

PMID- 9548409
TI  - The tachykinin NK1 receptor antagonist, RP67580, inhibits the bradykinin-induced
      rise in intracellular Ca2+ concentration in bovine pulmonary artery endothelial
      cells.
AB  - The bradykinin-induced rise in intracellular Ca2+ concentration ([Ca2+]i) and the
      bradykinin receptor involved in this response were characterized in bovine
      pulmonary artery endothelial cells. It was found that bradykinin induces an
      intracellular biphasic Ca2+ response, consisting of a transient peak followed by
      an elevated plateau phase. Both bradykinin and the bradykinin B1 receptor
      agonist, des-Arg9-bradykinin, induced a concentration-dependent increase in
      [Ca2+]i, but the bradykinin-induced rise was much greater. Moreover, the
      bradykinin-induced [Ca2+]i rise could be inhibited by the bradykinin B2 receptor
      antagonists, D-Arg0[Hyp3, Thi(5,8), D-Phe7]bradykinin and Hoe 140 (D-Arg[Hyp3,
      Thi5, D-Tic7, Oic8]bradykinin), but not by the bradykinin B1 receptor antagonist,
      des-Arg9-[Leu8]bradykinin. From these results it can be concluded that a
      bradykinin B2 receptor is involved in this response. Furthermore, we found that
      the tachykinin NK1 receptor antagonist, RP67580 ([imino 1 (methoxy-2-phenyl)-2
      ethyl]-2 diphenyl 7,7 perhydroisoindolone-4 (3aR, 7aR)), and its negative
      enantiomer, RP68651 (2-[1-imino 2-(2 methoxy phenyl) ethyl] 7,7 diphenyl 4
      perhydroisoindolone (3aS-7aS)), could inhibit the bradykinin-induced [Ca2+]i
      response, although no functional tachykinin NK1 receptors were found. Binding
      studies evidenced no binding of RP67580 or RP68651 to the bradykinin receptor. We
      conclude that RP67580 inhibits the bradykinin-induced rise in [Ca2+]i via a
      bradykinin B2 receptor-independent mechanism.

PMID- 9548408
TI  - Inhibition of recombinant human cardiac L-type Ca2+ channel alpha1C subunits by 3
      isobutyl-1-methylxanthine.
AB  - Inhibition of ion channels by the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX) and related compounds has been demonstrated in various cell
      types, including the neuromuscular junction, GH3 cells and vascular smooth muscle
      cells. These effects may be unrelated to the actions of these compounds on
      cellular metabolism, intracellular Ca2+ stores and phosphodiesterase inhibition.
      In this study, the inhibition of recombinant human cardiac L-type Ca2+ channel
      alpha1C subunits by IBMX was examined using the whole-cell configuration of the
      patch clamp technique. Inhibition was repeatable, voltage-independent and
      associated with increased apparent channel inactivation. The actions of IBMX were
      unaffected in the presence of inhibitors of protein kinases A and G. The non
      xanthine phosphodiesterase inhibitor rolipram had a small inhibitory effect on
      currents, but this was also unaffected by a protein kinase A inhibitor. These
      effects of IBMX could not be attributed to release of Ca2+ from intracellular
      stores. Our findings indicate that methylxanthines can inhibit the cardiac L-type
      Ca2+ channel alpha1C subunit in the absence of auxiliary subunits by an
      undetermined, possibly direct mechanism.

PMID- 9548410
TI  - Adaptation of cortical NMDA receptors by chronic treatment with specific
      serotonin reuptake inhibitors.
AB  - Glycine displaces [3H]CGP-39653 ([3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3
      pentenoic acid) binding to the glutamate recognition site with both high and low
      affinity. We reported previously that chronic treatment with antidepressants
      reduced the proportion of high to low affinity sites, or, even eliminated the
      high affinity sites in case of citalopram. Here, we compared the effects of
      citalopram with another serotonin specific reuptake inhibitor, fluoxetine on this
      measure. Chronic administration of citalopram or fluoxetine eliminated high
      affinity glycine-displaceable [3H]CGP-39653 binding to the mouse cortex in 78 and
      56% of animals, respectively, indicating that selective serotonin reuptake
      inhibitors produce qualitatively similar adaptive changes at NMDA receptors, that
      differ from other antidepressants in this neurochemical measure.

PMID- 9548411
TI  - Inhibition of ornithine decarboxylase by ifenprodil.
AB  - Ifenprodil (NMDA receptor antagonist) was tested as an inhibitor of ornithine
      decarboxylase. It was found that ifenprodil inhibited ornithine decarboxylase
      activity with the same potency as alpha-difluoromethylornithine, a major
      inhibitor of ornithine decarboxylase. This result suggests that ifenprodil could
      target either the polyamine site on the NMDA receptor complex or/and polyamine
      biosynthesis.

PMID- 9548412
TI  - Expression of dipeptidylaminopeptidase IV/CD26 in peripheral blood lymphocytes of
      hemophilic subjects.
AB  - CD26 antigen, a 110 kDa membrane glycoprotein with exopeptidase activity (DAP
      IV), is an activation marker of T lymphocytes preferentially expressed on CD4+
      memory cells and involved in T cell proliferation and IL-2 production after
      antigenic stimulation. We employed cytochemical and immunocytochemical techniques
      to study DAP IV/CD26 expression in circulating lymphocytes from 40 hemophilic
      patients, chronically treated with coagulation factors, in order to verify the
      possible involvement of this molecule in the immunological alterations of
      hemophilia. In all the hemophiliacs DAP IV activity was significantly lower than
      in the controls, independently of the quantity of blood transfused and previous
      exposure to viruses. This reduction may be responsible for the impaired
      proliferative response of lymphocytes to antigens and mitogens, notoriously
      observed in hemophilia. Whereas in the group of HIV- patients CD26 expression was
      similar to that of normal controls, in the 8 HIV+ hemophilic patients both
      percentages of positive lymphocytes and intensity of staining were significantly
      lower. In only 4 of the 8 cases was this deficit associated with CD4+ cell
      depletion. The significant selective loss of CD26 expression observed in HIV+
      patients is probably an early event after HIV infection and seems to occur even
      before CD4 cell depletion. In conclusion, evaluation of DAP IV/CD26 might be a
      useful option for monitoring the immunological alterations of all hemophilic
      patients, HIV positive or not, chronically treated with coagulation factors.

PMID- 9548413
TI  - Circulating CD34+ cells in cord blood and mobilized blood have a different
      profile of adhesion molecules than bone marrow CD34+ cells.
AB  - The expression of adhesion molecules was studied on CD34+ hematopoietic
      precursors in cord blood, bone marrow and mobilized blood. The samples were
      labeled in a double immunofluorescence procedure with a CD34 monoclonal antibody
      and with antibodies against maturation and differentiation antigens and adhesion
      molecules. Myeloid precursors formed the majority of the CD34+ cells in all
      samples. In bone marrow a separate cluster of B-cell precursors with low forward
      scatter was present. Nearly all CD34+ cells in normal bone marrow expressed VLA-4
      and VLA-5, PECAM-1, LFA-3 and HCAM. The majority of the CD34+ cells also had LFA 
      1 and L-selectin on the surface membrane. A small subset was VLA-2, VLA-3, ICAM-1
      or Mac-1 positive. CD34+ cells expressing the vitronectin receptor or the CD11c
      antigen were rare. Cord blood and mobilized blood CD34+ cells had a lower
      expression of VLA-2, VLA-3 and VLA-5 and a higher expression of LFA-1, ICAM-1 and
      L-selectin than bone marrow CD34+ cells. Except for LFA-1, this was not due to
      the presence of more myeloid precursors in these samples. Low beta1 integrin
      expression may lead to less adhesion to the extracellular matrix. High expression
      of L-selectin may facilitate interaction with endothelial cells. Therefore, this
      phenotype may favour mobilization.

PMID- 9548414
TI  - Inv(16) acute myeloid leukemia cells show an increased sensitivity to cytosine
      arabinoside in vitro.
AB  - Karyotype represents the major independent prognostic factor for response and
      remission duration in acute leukemia. In particular, it has been reported that
      acute myeloid leukemia (AML) patients with inv(16) abnormality show a better
      prognosis, especially in case of treatment with high-dose Ara-C (HD Ara-C)
      containing regimens. In this study we aimed at testing whether leukemic cells
      from patients showing the inv(16) were more sensitive to Ara-C in vitro, compared
      to AML blasts from patients with normal karyotype or chromosomal abnormalities
      other than t(15;17) or t(8;21). We analyzed blast cells from 30 patients who were
      diagnosed and treated in our institution. The IC50 of Ara-C, as tested by the XTT
      colorimetric assay, was significantly lower in cases with inv(16) (18.5+/-15.88
      micromol/l vs. 38+/-14.6 micromol/l,in cases with other abnormalities, p=0.01).
      This result was confirmed by a higher incorporation of [3H]-Ara-C into DNA
      (p=0.02 and p=0.001 compared to samples with normal and abnormal karyotype,
      respectively). All the same, Ara-C induced apoptosis was significantly increased
      in cells from patients with inv(16). Our data suggest a possible interaction
      between the molecular background of inv(16) and a modification of intracellular
      metabolism of Ara-C, and could thus provide a rationale for HD-Ara-C-based
      schedules for patients with inv(16) AML.

PMID- 9548415
TI  - Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for
      Hodgkin's disease: a prospective study.
AB  - This study presents the results of a prospective study of methyl-gag, ifosfamide,
      methotrexate and etoposide (MIME) as salvage regimen for Hodgkin's disease (HD)
      in Sweden. Sixty-four patients with recurrent or refractory HD were treated with
      MIME between July 1988 and December 1993. All patients except one had, earlier,
      been treated with and failed consecutive or alternating MOPP and ABVD. Median age
      was 37 yr (range 14-73). Twenty patients (31%) achieved a complete remission (CR)
      and 17 (27%) a partial remission (PR), giving an overall response rate of 58%.
      The 5-yr survival for all patients was 43%. In a multivariate analysis, the most
      important factors predicting a poor survival were the presence of extranodal
      disease at relapse, male gender and high age. Twenty-nine patients were treated
      with high-dose chemotherapy with stem-cell rescue after MIME. Those patients had
      a similar survival compared to the patients responding to MIME but not treated
      with high-dose chemotherapy. We conclude that MIME induces remissions in a high
      proportion of patients with recurrent and refractory HD with acceptable toxicity.
      The remissions probably need consolidation, but the nature of this consolidation
      is still controversial.

PMID- 9548416
TI  - Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine
      synergize to enhance haematopoietic reconstitution in irradiated mice.
AB  - The activation of adenosine receptors has recently been demonstrated to stimulate
      haematopoiesis. In the present study, we investigated the ability of drugs
      elevating extracellular adenosine to influence curative effects of granulocyte
      colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of
      60Co radiation. Elevation of extracellular adenosine in mice was induced by the
      combined administration of dipyridamole, a drug inhibiting the cellular uptake of
      adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects
      of dipyridamole plus AMP, and G-CSF, administered either alone or in combination,
      were evaluated. The drugs were injected to mice in a 4-d treatment regimen
      starting on d 3 after irradiation and the haematopoietic response was evaluated
      on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the
      late maturation stages of blood cells, appearing shortly after the completion of
      the treatment, were not influenced by dipyridamole plus AMP, positive effects of
      the combination therapy occurred in the post-irradiation recovery phase which is
      dependent on the repopulation of haematopoietic stem cells. This was indicated by
      the significant elevation of counts of granulocyte-macrophage progenitor cells
      (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14),
      granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils
      (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood.
      These effects suggest that the repopulation potential of the combination therapy
      lies in a common multilineage cell population. The results of this study
      implicate the promising possibility to enhance the curative effects of G-CSF
      under conditions of myelosuppressive states induced by radiation exposure.

PMID- 9548417
TI  - Circadian-based effects of AcSDKP, with or without rhG-CSF on hematologic
      toxicity of chemotherapy in mice.
AB  - The hematologic toxicity of arabinosylcytosine (Ara-C) and carboplatin (CBDCA) as
      well as the stimulating effect of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) on murine bone marrow vary according to their dosing
      time along the 24-h time scale. In the present study, we investigated whether the
      tolerability of Ara-C or CBDCA, given at their least toxic circadian time, could
      be improved further with AcSDKP, a negative regulator of hemopoiesis, rhG-CSF or
      both. A total of 228 B6D2F1 mice received once-daily injection of either Ara-C
      (42 mg/kg/d s.c.) for 7 d (d 0-6) at 8 hours after light onset - HALO) or CBDCA
      (40 mg/kg/d i.p.) for 5 d (d 2-6) at 16 HALO. AcSDKP (24 microg/d) was
      continuously infused for 7 d (d 0-6), using an osmotic minipump. rhG-CSF (400
      microg/kg/d s.c.) was injected for 4 d (d 9-12) at 9 HALO. Subgroups of mice were
      sacrificed at 3 HALO on various days following treatment. AcSDKP significantly
      increased CFU-GM count on d 7 and leukocyte, neutrophil and monocyte counts on d
      13 and d 16 compared to Ara-C alone. Also, rhG-CSF produced similar protective
      effects to those of AcSDKP with regard to leukocyte and CFU-GM counts. The
      combination of AcSDKP with rhG-CSF induced a further increase in total leukocytes
      and their subsets as compared to either agent alone, but did not alter the CFU-GM
      counts. Neither AcSDKP nor rhG-CSF nor their combination reduced CBD CA-induced
      hematological toxicity. In conclusion, AcSDKP or rhG-CSF administration further
      improved the tolerability of Ara-C beyond that already achieved with optimal
      circadian timing, while no such effect was observed in mice receiving CBDCA at
      the dose used. The results warrant further exploration of chronopharmacologic
      delivery schedules combining Ara-C with AcSDKP.

PMID- 9548418
TI  - Modulatory function on autologous myeloid progenitor cells of clonal T
      lymphocytes following autologous bone marrow transplantation.
AB  - We have studied the regulatory capacity of clonal T-lymphocytes from patients
      undergoing autologous bone marrow transplantation (ABMT) on the generation of CFU
      GM from their harvest marrow preparations. To this end, T-lymphocytes from
      peripheral blood from 5 patients undergoing ABMT isolated 10 d before and 7, 14
      and 28 d post-ABMT were placed in limiting dilution conditions (384 wells for
      each patient at each time point) and polyclonally stimulated. From more than 1600
      wells with growth from the 5 patients, preparations from more than 900 wells
      could be expanded (range between patients 33-452) and identified by
      immunophenotyping (IP) and flow cytometry (FCM) by their exclusive expression of
      CD4 or CD8. This was significantly fewer than seen in normal donors, especially
      so at d 7 and 14 post-ABMT The ratio between CD4+ and CD8+ clones varied between
      0.6 and 2.8 (median 1.3) and was significantly lower in the patients compared to
      normal donors (median 3.1; range 3.0-6.5). When the clonal T-cell preparations
      were co-cultured with autologous bone marrow cells obtained at the time of
      harvest and depleted for T-lymphocytes, the vast majority of both CD4+ and CD8+
      clones exerted a clear enhancement on the CFU-GM growth with no relation to time
      of blood sampling in its the magnitude. Moreover, a trend seen in the normal
      donors towards CD4+ clones being more effective in this enhancement was not
      observed in ABMT patients. We conclude that clonal T-cells from ABMT patients,
      irrespective of their phenotype and time of isolation, exert an enhancement on
      the growth of autologous CFU-GM, which is equal to that seen in normal donors.

PMID- 9548419
TI  - Analysis of the granulocyte colony-stimulating factor receptor gene structure
      using PCR-SSCP in myeloid leukemia and myelodysplastic syndrome.
AB  - The membrane-proximal cytoplasmic region of the granulocyte colony-stimulating
      factor receptor (G-CSFR) is known to be essential for the proliferation signal,
      with a more distal region being required for the differentiation signal. Such a
      separation of functional domains raises the possibility that mutations occurring
      at these regions may contribute to cell proliferation in the absence of
      differentiation, this being the most important characteristic in acute leukemia
      cells. Therefore, we analysed the structural abnormalities at the transmembrane
      and cytoplasmic region of G-CSFR in a significant number of patients with various
      myeloid malignancies. When we examined the genomic DNA of G-CSFR obtained from 41
      patients with acute myelogenous leukemia (AML), 18 with chronic myelogenous
      leukemia (CML), 7 with myelodysplastic syndrome (MDS), 2 with chronic
      myelomonocytic leukemia and 1 with chronic neutrophilic leukemia, we found a
      polymorphism in 3 patients, but no significant pathogenic mutations in any
      patients. The screening for this polymorphism in 100 hematologically normal
      controls revealed that it may be useful as a linkage marker for population and
      family studies, because the heterozygosity index is at a high level (0.055).
      While there have been several reports discussing the leukemogenic potential of
      mutations in the cytokine/hematopoietin receptor superfamily, genetic alterations
      in the transmembrane and cytoplasmic region of G-CSFR do not seem to play a
      pathogenic role in leukemia.

PMID- 9548420
TI  - An unusual case of familial aplastic anaemia: in vitro and in vivo evidence for a
      multipotent progenitor responsive to G-CSF.

PMID- 9548421
TI  - Pancytopenia in infants of aplastic anaemic mothers: case report.

PMID- 9548422
TI  - Veto cell suppression mechanisms in the prevention of allograft rejection.
AB  - Substantial evidence has accumulated to suggest that in the near future
      implementation of the veto-cell-suppressor concept in the treatment of kidney
      allograft recipients might lead to the establishment of life-long specific
      allograft tolerance in the absence of further immunosuppressive therapy. Veto
      suppression prevents the generation of antigen-specific T-helper and cytotoxic T
      lymphocytes in vitro provided that the T-lymphocyte precursors specifically
      recognize antigenic peptides associated with the major histocompatibility complex
      molecules class II and class I, respectively, expressed on the surface of the
      veto-active cell. Data from a large number of experimental and clinical studies
      strongly indicate that veto-active cells function in vivo and are capable of
      preventing allograft rejection. Thus, donor-cell-mediated veto activity is the
      most likely explanation for the well-known graft tolerizing effect of
      pretransplant donor blood transfusions in kidney graft recipients. A prerequisite
      for a veto-active environment in vivo is the establishment of lymphoid
      microchimerism, in which veto-active donor and recipient cells mutually
      downregulate potential alloaggression.

PMID- 9548424
TI  - Renal structural changes in insulin-dependent diabetic patients with albuminuria.
      Comparison of cases with onset of albuminuria after short or long duration.
AB  - The large interindividual variation in diabetes duration until the onset of
      nephropathy is partly unexplained. This study was performed to compare renal
      structure in insulin-dependent (IDDM) patients who had developed signs of
      nephropathy after a short or long duration of diabetes. Renal biopsies were
      obtained from 17 IDDM patients, with albumin excretion rate 20-300 microg/min and
      normal blood pressure. Six patients had <25 years duration ("short-term", early
      onset of microalbuminuria) and eight patients had duration >30 years ("long
      term", late onset of microalbuminuria). Biopsies were obtained 18 months after
      entry into a study testing the effect of low-dose antihypertensives. Parameters
      characterizing diabetic glomerulopathy were significantly increased in IDDM
      patients compared with those in 17 living donors: Basement membrane thickness,
      mean and (CV): 591 nm (0.17) vs 320 nm (0.12), mesangial volume fraction per
      glomerulus 0.27 (0.19) vs 0.19 (0.10), matrix volume fraction per glomerulus 0.16
      (0.20) vs 0.097 (0.22), matrix star volume 38.5 microm3 (0.43) vs 13.9 microm3
      (0.31), (p<10(-4) for each). Comparison of short vs long-term patients showed no
      significant differences in glomerulopathy parameters, glomerular volume or
      extracellular material per glomerulus, whereas the fraction of occluded glomeruli
      was significantly increased in long-term patients. A close correlation obtained
      between fraction of occluded glomeruli and glomerular filtration rate (r=0.72, p=
      0.001). Glomerular occlusion occurred unrelated to the severity of diabetic
      glomerulopathy. It is suggested that diabetic macroangiopathy and arteriolar
      hyalinization may play an important role in the renal function of patients with
      slow development of nephropathy.

PMID- 9548423
TI  - T-cell subsets in adenoids and peripheral blood related to age, otitis media with
      effusion and allergy.
AB  - Adenoids and peripheral blood samples from 29 children (20-120 months of age)
      undergoing adenoidectomy for long-standing otitis media with effusion (OME)
      (n=16) or obstructive adenoid hyperplasia (n=13) were investigated by flow
      cytometry for their T-lymphocyte profile. Eleven of the enrolled children were
      allergic to inhalant and/or food allergens. For the whole group, the percentage
      of helper T cells belonging to the memory phenotype (CD4+/CD45RO+ cells) was
      significantly higher in adenoids than in blood (p<0.0001), while the same cell
      category increased with age in peripheral blood (p<0.01). A highly significant
      negative regression (p<0.001) was found between age and the percentage ratio of
      CD4+ cells that were CD45RO+ in adenoids and blood. Allergic children had a
      higher CD4+/CD8+ ratio for cells expressing CD45RO+ (p<0.05) in adenoids. The
      results of this study indicate that adenoids participate in the development of an
      immunological memory. Our findings support a relationship between allergy and
      memory cells in adenoids.

PMID- 9548425
TI  - Molecular genetic analysis of easily accessible breast tumour DNA, purified from
      tissue left over from hormone receptor measurement.
AB  - In order to establish a large panel of normal and tumour DNA from primary breast
      cancer patients, we looked for a source of easily accessible, good quality breast
      tumour DNA. Following routine hormone receptor analysis at the hospital the
      leftover pellets contained the nuclei from the tumour tissue. We collected 670
      pellets over a period of 2 1/4 years and isolated a large amount of DNA (on
      average 400 microg per pellet). To control the quality of this tumour DNA, we
      analysed 41 pellets and matching normal DNA for loss of heterozygosity (LOH),
      with 11 microsatellite markers along chromosome 17. This chromosome is well
      described for breast cancer. LOH is a sensitive method, requiring good quality
      and pure tumour DNA. Contamination with normal DNA will blur the results. We
      found a high rate of LOH, ranging from 33 to 74%, which is in agreement with
      other reports, and therefore recommend this rich source of breast tumour DNA for
      molecular biological analysis.

PMID- 9548426
TI  - Autopsy-verified venous thromboembolism within a defined urban population--the
      city of Malmo, Sweden.
AB  - OBJECTIVE: To analyse the frequency of autopsy-proven venous thromboembolism
      within a defined region and evaluate if certain risk groups not earlier
      recognized could be found. The incidence of objectively diagnosed venous
      thromboembolism was also calculated. SETTING: The city of Malmo, Sweden, with
      230,000 inhabitants. MAIN OUTCOME MEASURE: Analysis of 2,356 autopsies for the
      year 1987 of deceased inhabitants from the city of Malmo (2,981 deceased, autopsy
      frequency 79.0%) regarding venous thromboembolism. RESULTS: 25% of autopsies
      revealed venous thromboembolism. At the acute-care hospital 31%, at the chronic
      hospital 37%, but in forensic autopsies of non-hospital deaths only 5% (p<0.001)
      revealed venous thromboembolism. Major pulmonary embolism was seen in 13% and was
      more frequent in in-hospital deaths (p<0.001). Two in-hospital and two non
      hospital deaths due to pulmonary embolism and fractures were found: two patients
      with knee fractures, one hip fracture and one ankle fracture patient. The
      incidence of objectively diagnosed venous thromboembolism (autopsy, phlebography,
      perfusion scintigraphy) was calculated and an incidence of 42.5/10,000
      inhabitants/year was found, (strongly age-dependent). CONCLUSION: Venous
      thromboembolism is a common finding in autopsies of hospitalized patients.
      Patients with fractures other than hip fractures are less well studied as regards
      venous thromboembolic complications. Further studies on these fracture patients
      are warranted.

PMID- 9548427
TI  - Evaluation of an immunohistochemical test with polyclonal antibodies raised
      against mycobacteria used in formalin-fixed tissue compared with mycobacterial
      specific culture.
AB  - An immunohistochemical (IH) test (commercially available polyclonal antiserum
      rabbit anti-Myco-bacterium bovis; DAKO A/S) was used to detect the presence of
      mycobacteria in 65 formalin-fixed, paraffin-embedded tissue blocks from different
      organs, showing necrotizing caseous granuloma lesions on hematoxylin and eosin
      sections from 65 patients. These 65 samples were dyed using an acid-fast
      fluorescent technique and compared using the immunohistochemical method. Both
      results were also compared with the mycobacterial cultures. The IH test, compared
      with the culture, showed a sensitivity (S) of 52%, a specificity (Sp) of 76%, a
      positive predictive value (PV pos) of 61% and a negative predictive value (PV
      neg) of 69%. We analyze these data and discuss the possible causes of false
      positive and -negative results of the IH test. This rapid test on paraffin
      embedded tissue seems valuable in the period when waiting for the culture
      results.

PMID- 9548428
TI  - Association between in vivo iododeoxyuridine labeling, MIB-1 expression,
      malignancy grade and clinical stage in human prostate cancer.
AB  - Large variability in the biological behavior of prostate cancer makes prognostic
      markers important. The extent of tumor cell proliferation has been suggested as
      an important predictor of clinical outcome. Fifty-five patients suspected of
      having or with previously diagnosed prostate cancer were labeled in vivo with
      IdUrd (a thymidine analogue incorporated into DNA in S-phase cells) by
      intravenous infusion before transurethral resection. IdUrd-labeled cells and MIB
      1-positive cells were detected by immunohistochemistry. We found statistically
      significant associations between the tumor cell proliferation rates measured by
      in vivo IdUrd labeling and MIB-1 expression in formalin-fixed paraffin-embedded
      tumors. Good correlations were also found between S-phase fraction, MIB-1
      expression, clinical stage and malignancy grade. These results make larger
      retrospective studies on archival tissue meaningful.

PMID- 9548429
TI  - Pyogenic hepatic abscess. A 10-year population-based retrospective study.
AB  - A 10-year retrospective survey was undertaken of patients with pyogenic hepatic
      abscesses (PHA). Fifty-two patients fulfilled the criteria of PHA, equivalent to
      a mean annual incidence of 11/1,000,000. The main symptom was fever. Laboratory
      tests were compatible with infection, slightly elevated alkaline phosphatase
      being the only test pointing towards the liver as the focus of infection. Forty
      one patients (79%, 95% CL, 68-90%) had positive cultures from aspirated pus, with
      a total of 79 isolates. Enteric Gram-negative rods accounted for 45% and
      anaerobic bacteria for 31% of PHA isolates. Gram-positive cocci, predominantly
      non-haemolytic streptococci, were the third largest group (19%), but were rare
      among blood isolates. Positive blood cultures were found in 21 patients (40%, 95%
      CL, 27-54%), with a total of 28 isolates. Percutaneous drainage was performed in
      26, percutaneous needle aspiration in 10, combinations thereof in 5, and
      abdominal surgery in 5. Forty-nine patients received systemic antibiotic therapy,
      four of whom were treated with antibiotics only. Seven recurrences occurred and
      the overall case fatality rate was 6% (95%, CL 0-12%), which might reflect a low
      rate of underlying malignant diseases in our study material.

PMID- 9548430
TI  - Primary mucosal melanomas of the nasal cavity and paranasal sinuses. A
      clinicopathological analysis of 14 cases.
AB  - We present 14 patients with primary sinonasal melanomas (SM) identified from 1984
      1997 in our archives (11/14 lateral nose, 1/14 nasal septum, 2/14 paranasal
      sinuses; 8M/6F, mean age 67.7 years, range 39-88 years). Survival was poor
      (median 9 months) with death related to extensive local disease and/or widespread
      hematogenous metastases. The following histological subtypes were identified in
      descending order: amelanotic small blue cell, pleomorphic, epithelioid, spindle
      cell and myxoid. High mitotic rate and vascular invasion, absence of tumor
      infiltrating lymphocytes and regression were features shared by all SM. Negative
      staining of B- and T-cell markers, LCA, neuroendocrine markers such as NSE,
      chromogranin and synaptophysin, and CK-negativity excluded olfactory
      neuroblastoma, small cell undifferentiated carcinoma, and lymphoma. S-100 protein
      was expressed in all SM, but demonstrated variable staining intensity with areas
      of complete negativity. HMB45 was strongly and uniformly (>80%) expressed in all
      undifferentiated small blue cell SM. The pigmented SM were predominantly HMB45
      negative. The strong HMB45 staining in amelanotic small blue cell SM is explained
      by the reaction of HMB45 antibody with an oncofetal antigen found in immature
      melanosomes. In these poorly differentiated amelanotic malignant melanomas,
      antibody to HMB45 proved to be a superb diagnostic marker. We therefore strongly
      advocate the inclusion of HMB45 antibody in the panel of antibodies for initial
      work-up of undifferentiated mucosal neoplasms, since a negative S-100 stain in
      small biopsy material may result in incorrect classification of these neoplasms.

PMID- 9548431
TI  - Coagulase-negative staphylococci in a major Danish university hospital: diversity
      in antibiotic susceptibility between wards.
AB  - Over a one-year period, all coagulase-negative staphylococci (CoNS) from blood
      cultures, cerebrospinal fluids and peritoneal effluents from patients in a major
      Danish university hospital were investigated for susceptibility to penicillin G;
      methicillin; gentamicin; netilmicin; amikacin; erythromycin; clindamycin; fusidic
      acid; rifampicin; tetracycline; chloramphenicol; ciprofloxacin; teicoplanin; and
      vancomycin. Among the CoNS-isolates, 56% were resistant to methicillin, 51% to
      gentamicin, 28% to ciprofloxacin, and 5% to teicoplanin. Blood culture CoNS
      isolates from patients with a central venous catheter (CVC) were more often
      resistant to various antibiotics compared to CoNS-isolates from patients without
      a CVC, e.g. methicillin (72% vs 21%), gentamicin (65% vs 22%) (p<0.00000001).
      Great diversity in antibiotic resistance between the wards was found; methicillin
      resistance (in most cases multiple antibiotic resistance) was in particular
      associated with consumption of broad-spectrum beta-lactams, quinolones, and total
      antibiotic consumption in a ward. Thus, the antibiotic policy of a ward is an
      important factor for antibiotic resistance among CoNS.

PMID- 9548432
TI  - Herpes simplex virus and human papillomavirus in a population-based case-control
      study of cervical intraepithelial neoplasia grade II-III.
AB  - In order to evaluate the association between seropositivity for herpes simplex
      virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we
      analysed data from a population-based case-control study of CIN grade II-III
      which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls.
      Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were
      independent risk factors for CIN, taking human papillomavirus exposure into
      account, and to elucidate the combined effect of HPV positivity and
      seropositivity for HSV In logistic regression analyses, the association between
      HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted
      OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In
      analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2
      increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1
      seropositivity was not significantly associated with CIN. In women positive for
      other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95%
      CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1
      nor HSV-2 seropositivity was associated with CIN. Compared to the reference group
      of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2
      negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in
      women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996).
      The estimate of interaction was strong, but did not reach significance, and our
      findings may suggest that the combined effect of the two viruses is of
      aetiological importance in cervical carcinogenesis. Furthermore, the results
      indicate that HPV DNA positivity is not sufficient to explain the sexual
      behaviour-associated risk of cervical neoplasia and that further studies on the
      role of genital HSV (type 1 as well as type 2) and other STDs are warranted.

PMID- 9548433
TI  - Role of tenascin in cancer development.

PMID- 9548434
TI  - Induction of glandular stomach cancers in Helicobacter pylori-sensitive Mongolian
      gerbils treated with N-methyl-N-nitrosourea and N-methyl-N'-nitro-N
      nitrosoguanidine in drinking water.
AB  - An animal model of stomach carcinogenesis was established using Mongolian gerbils
      with N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      as the carcinogens. In addition, the sensitivity of these gerbils to Helicobacter
      pylori (H. pylori) was confirmed. One hundred and sixty specific pathogen-free
      male MGS/Sea animals, 7 weeks old, were treated with MNU in the drinking water
      (30 ppm for alternate weeks to give 10 weeks exposure, or 10 ppm or 3 ppm for 20
      weeks continuous exposure), or given MNNG in the drinking water at 400 ppm or 200
      ppm for 20 weeks, or orally inoculated with ATCC43504 H. pylori (1.7 x 10(8)
      CFUs/animal). Adenocarcinomas in the glandular stomach were found in 2 out of 12
      effective animals (2/ 12) treated with 30 ppm MNU at week 20, although all were
      dead or moribund by week 30 due to MNU toxicity. At week 50, the incidences of
      gastric adenocarcinomas in groups treated with 10 ppm MNU, 3 ppm MNU, 400 ppm
      MNNG, and 200 ppm MNNG were 2/21 (9.5%), 1/23 (4.3%), 7/ 11 (63.6%), and 1/10
      (10.0%). The lesions were generally well differentiated, although poorly
      differentiated adenocarcinoma was also found in a single gerbil in each of the 10
      ppm MNU and 400 ppm MNNG groups. In control animals no tumors were found. In the
      infection study, the animals were killed at week 20, and H. pylori was detected
      in all cases, causing multiple erosions with marked inflammatory cell
      infiltration in the lamina propria and submucosa, and frequent formation of
      lymphoid follicles. Thus, MNU and MNNG in the drinking water induced neoplastic
      lesions in the glandular stomach epithelium of H. pylori-sensitive gerbils.

PMID- 9548435
TI  - Induction of squamous cell carcinomas in the salivary glands of rats by potassium
      iodide.
AB  - In a 2-year carcinogenicity study of potassium iodide (KI) in F344/DuCrj rats,
      squamous cell carcinomas (SCCs) were observed in the salivary glands of 4/40
      males and 3/40 females receiving 1000 ppm KI in the drinking water. Ductular
      proliferation with lobular atrophy was observed at high incidence in the
      submandibular glands of the high-dose animals, and squamous metaplasia was
      frequently evident within the proliferative ductules and the larger interlobular
      ducts. A transition from metaplasia to SCC was apparent. The results suggest that
      squamous metaplasia in proliferative ductules, occurring secondarily to lobular
      impairment induced by KI, may develop into SCCs via a non-genotoxic,
      proliferation-dependent mechanism.

PMID- 9548436
TI  - Up-regulation of p27Kip1 correlates inversely with anchorage-independent growth
      of human cancer cell lines.
AB  - We examined the correlation between anchorage-independent growth and cell cycle
      related molecules using 39 human cancer cell lines. They consisted of lung-,
      colon-, stomach-, breast-, ovarian-, brain-, renal- and melanoma-derived cell
      lines. Their anchorage-independent growth ability varied, but was not clearly
      related to the tissue of origin. There was a tendency for the levels of cyclin
      D1, cyclin E, cyclin A, p27, and p21 to show a tissue-dependent expression
      pattern. Statistical analysis revealed an inverse correlation of the p27 level
      with anchorage-independent growth (r=-0.456, P<0.01). Thus, the regulation of p27
      is suggested to be linked to the anchorage independence of human cancer cells.

PMID- 9548437
TI  - Risk factors for benign breast disease according to histopathological type:
      comparisons with risk factors for breast cancer.
AB  - We evaluated risk factors for benign breast disease by using a case-control study
      method. The series was taken from participants in breast cancer screening
      programs during 1978-1986 in Miyagi Prefecture, Japan. All benign breast lesions
      diagnosed during this period were reviewed and reclassified into proliferative
      and non-proliferative types based on the Dupont and Page classification. Data on
      382 benign breast disease cases (130 proliferative-type cases and 252 non
      proliferative-type cases) and 1,489 screening year-, age- and screening area
      matched normal controls were used for analysis. Nulliparity or low parity and
      family history of breast cancer in mother or sisters were significantly
      associated with an increased risk of proliferative type. Premenopausal status was
      significantly associated with an increased risk of non-proliferative type. No
      significant association with history of lactation for the last child was observed
      in either type, but the risk of proliferative type increased with increasing
      duration of lactation (P=0.08). A comparison between the present findings and the
      risk factors for breast cancer indicated epidemiologic similarities between
      proliferative benign and malignant breast lesions in general. The associations of
      these two lesions with lactation patterns were, however, dissimilar.

PMID- 9548438
TI  - Calcium, magnesium, and nitrate in drinking water and gastric cancer mortality.
AB  - The possible association between the risk of gastric cancer and the levels of
      calcium, magnesium, and nitrate in drinking water from municipal supplies was
      investigated in a matched case-control study in Taiwan. Records of gastric cancer
      deaths among eligible residents in Taiwan from 1987 through 1991 were obtained
      from the Bureau of Vital Statistics of the Taiwan Provincial Department of
      Health. Controls were deaths from other causes and were pair-matched to the cases
      by sex, year-of-birth, and year-of-death. Each matched control was selected
      randomly from the set of possible controls for each case. Data on calcium,
      magnesium, and nitrate levels in drinking water throughout Taiwan were obtained
      from the Taiwan Water Supply Corporation. The municipality of residence of the
      cases and controls was assumed to be the source of the subject's calcium,
      magnesium, and nitrate exposure via drinking water. The subjects were divided
      into tertiles according to the levels of calcium, magnesium, and nitrate in their
      drinking water. The results of the present study show that there is a significant
      positive association between drinking water nitrate exposure and gastric cancer
      mortality. The present study also suggests that there was a significant
      protective effect of calcium intake from drinking water on the risk of gastric
      cancer. Magnesium also exerts a protective effect against gastric cancer, but
      only for the group with the highest levels.

PMID- 9548439
TI  - Enhancing effects of quinacrine on development of hepatopancreatic lesions in N
      nitrosobis(2-oxopropyl)amine-initiated hamsters.
AB  - The modifying effects of quinacrine administration during the post-initiation
      phase of carcinogenesis were investigated in hamsters treated with N-nitrosobis(2
      oxopropyl)amine (BOP). Female Syrian hamsters were given three weekly s.c.
      injections of BOP at a dose of 10 mg/kg and then 300 or 100 ppm quinacrine in
      their diet for 37 weeks. Additional groups of animals received the BOP injection
      alone, or only the 300 ppm quinacrine treatment as BOP-negative controls. At week
      40 of the experiment, all surviving animals were killed and development of
      proliferative lesions was assessed histopathologically. The multiplicity of
      pancreatic adenocarcinomas and dysplastic lesions per hamster was significantly
      higher (P<0.01 and P<0.05) in the BOP/Q100 group (1.92 and 1.78) than in the BOP
      alone group (1.07 and 0.79). The incidence of hepatocellular adenomas plus
      carcinomas was also significantly elevated (P<0.05) in the BOP/Q300 and BOP/Q100
      groups. In contrast, the multiplicity of lung adenomas plus adenocarcinomas was
      significantly decreased (P<0.05) by the Q300 treatment. Neither the incidence nor
      the multiplicity of renal cell tumors (adenomas and carcinomas) or
      nephroblastomas significantly differed between the BOP-treated groups. Electron
      microscopic examination revealed an abundance of myeloid lamellar bodies filling
      the cytoplasm of hepatocytes and pancreatic ductular and acinar cells, and
      epithelial cells of the gallbladder in the quinacrine-treated animals, the degree
      being dose-dependent. Our results indicate that quinacrine enhances pancreatic
      and hepatic carcinogenesis in hamsters induced by BOP.

PMID- 9548440
TI  - Chemoprevention of N-nitroso-N-methylurea-induced rat mammary carcinogenesis by
      soy foods or biochanin A.
AB  - We examined the effects of soybeans, a soy product (miso) and biochanin A, an
      isoflavone derivative, on N-nitroso-N-methylurea (MNU)-induced rat mammary
      carcinogenesis. Seven-week-old female CD/Crj rats received a single i.v. dose (40
      mg/kg body weight) of MNU. After administration of MNU, rats were fed diet
      containing 0% (control), 2% or 10% soybeans, or 10% miso as a soy-supplemented
      diet, or 10 or 50 mg/kg biochanin A. All rats were observed for 18 weeks after
      MNU administration. At 18 weeks, the multiplicity (mean tumors/rat) of palpable
      mammary tumors was significantly decreased in the 10% soybean (1.1) and 10% miso
      (1.2) diet groups compared to the control (2.2) (P<0.05, respectively). In the
      biochanin A-supplemented diet groups, the incidence (percentage of rats with
      tumors) was significantly decreased in the 50 mg/kg (32%) diet group compared to
      the control (80%) (P<0.01), and the multiplicity was significantly decreased in
      both the 10 mg/kg (0.7) and 50 mg/kg (0.5) diet groups compared to the control
      (2.2) (P<0.01 and P<0.001, respectively). The proliferative cell nuclear antigen
      labeling index of mammary tumors was significantly decreased in both biochanin A
      supplemented diet groups compared to the control. The present results indicate
      that soybeans, miso, and biochanin A are useful for the prevention of mammary
      cancer.

PMID- 9548441
TI  - Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of
      carcinogen-induced hepatic nodules in rats.
AB  - Tumor metastasis can be prevented by inhibiting angiogenesis. In the present
      study, we have demonstrated that the angiogenesis inhibitor TNP-470 also
      suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was
      performed by the feeding of 2-acetylaminofluorene to hepatectomized rats during 8
      14 weeks of age. Predominantly arterial-to-portal circulation and sinusoidal
      capillarization were determined by the staining of nodules with arterially
      infused ink and immunostaining for factor VIII-related antigen, respectively.
      Intraperitoneal administration of 30 mg/kg b.w. of TNP-470 twice a week
      significantly reduced the number of hepatic nodules. Among the nodules,
      hyperplastic nodules stained with ink, atypical hyperplastic nodules and
      hepatocellular carcinoma, all of which possess structurally altered sinusoidal
      endothelial cells or capillary-type endothelial cells, were dramatically
      decreased in number. Suppression was observed equally in nodules of all sizes.
      TNP-470 was more effective when administered during 8-20 weeks than during 14-26
      weeks. In contrast, ink-non-stained hyperplastic nodules, which have normal
      sinusoidal endothelial cells, were not affected at all. The present results
      indicate that TNP-470 suppresses the development of primary hepatic nodules whose
      microvessels are capillaries or transitional forms from sinusoids to capillaries.

PMID- 9548442
TI  - Transgenic mouse expressing a full-length hepatitis C virus cDNA.
AB  - Hepatitis C virus (HCV), a major causative agent of post transfusion non-A, non-B
      hepatitis (NANBH), can only infect humans and chimpanzees. We produced nine
      transgenic mouse lines carrying a full-length HCV cDNA with the human serum
      amyloid P component (hSAP) promoter that can direct liver-specific expression. In
      one of these lines HCV mRNA and HCV core protein were detected in the liver of
      the transgenic mouse, although the levels of expression were very low. In
      addition, HCV-related antibody was detected in the serum.

PMID- 9548444
TI  - Globotriaosyl ceramide and globoside as major glycolipid components of
      fibroblasts in scirrhous gastric carcinoma tissues.
AB  - Scirrhous gastric cancer is characteristic in that cancer cells proliferate and
      invade with prominent fibrosis. To search for the expression of specific
      carbohydrate chains in scirrhous gastric cancer, we have examined the
      glycosphingolipid composition of scirrhous cancer tissues (n=10) in comparison
      with that of non-scirrhous cancer tissues (n=10) by means of two-dimensional thin
      layer chromatography, followed by fast atom bombardment mass spectrometry of the
      individual glycolipids and immunostaining analysis. The major neutral
      glycosphingolipids from scirrhous gastric cancer tissues were identified as
      ceramide monohexoside, ceramide dihexoside, globotriaosyl ceramide (Gb3) and
      globoside (Gb4), while the major acidic glycosphingolipids were II3 NeuAcalpha
      LacCer, II3 NeuAcalpha2-LacCer and sulfatide. Relative concentrations of Gb3 and
      Gb4 in scirrhous gastric cancer tissues (Gb3 + Gb4 = 58%) were two times higher
      than those in non-scirrhous gastric cancer tissues (29%). Orthotopic fibroblasts
      cloned from scirrhous gastric cancer tissues showed similar high concentrations
      of Gb3 and Gb4 to scirrhous gastric cancer tissues. Furthermore,
      immunohistochemical study revealed that Gb3 and Gb4 were expressed intensely on
      the fibroblasts. On the other hand, analysis of glycosphingolipids in four
      scirrhous gastric cancer cell lines yielded the following results. i) The
      contents of Gb3 and Gb4 were low (6%), compared with orthotopic fibroblasts
      (62%). ii) Significant amounts of Le(a) (pentaglycosylceramide) and Le(b) (hexa-
      and heptaglycosylceramides), which could not be detected in scirrhous cancer
      tissues, were observed. The results show that the major neutral
      glycosphingolipids such as Gb3 and Gb4 of scirrhous gastric cancer tissues were
      derived from orthotopic fibroblasts and not from the cancer cells.

PMID- 9548443
TI  - Cyclin D1 overexpression detected by a simple competitive reverse transcription
      polymerase chain reaction assay for lymphoid malignancies.
AB  - t(11;14)(q13;q32) observed in B-cell malignancies is associated with cyclin D1
      (bcl-1, PRAD1, CCND1) overexpression. We devised a simple competitive reverse
      transcription-polymerase chain reaction (RT-PCR) assay for rapid detection of
      cyclin D1 overexpression. Sharing a single upstream primer derived from a
      homologous sequence in cyclins D1, D2 and D3, each PCR product serves as a
      competitor and cyclin D1 overexpression is determined by comparing the
      intensities of the three amplified products. We analyzed cyclin D1 in clinical
      specimens from 104 patients with lymphoid malignancies. Cyclin D1 overexpression
      was evident in 13 of 104 (7/72 non-Hodgkin's lymphomas, 0/6 adult T-cell
      lymphoma/leukemias, 0/4 Hodgkin's diseases, 0/11 acute lymphoblastic leukemias,
      3/4 multiple myelomas, 1/2 Waldenstrom's macroglobulinemias, 1/2 prolymphocytic
      leukemias and 1/3 chronic lymphocytic leukemias). Among 72 patients for whom
      cytogenetic studies had been done, all 7 patients with t(11;14) were positive.
      The relative expression levels of D-type cyclins altered dramatically in the
      presence of t(11;14). Thus, this RT-PCR assay can identify tumors with cyclin D1
      overexpression. Cyclin D1 overexpression was frequent in extranodal specimens (11
      out of 32 vs. 2 of 72 lymph nodes) and was restricted to specific types of
      lymphoid malignancies, as observed using other methods. This reliable assay
      should be suitable to provide clinical guidance for the diagnosis and management
      of lymphoid malignancies, especially in the case of extranodal involvement.

PMID- 9548445
TI  - Homotypic adhesion through carcinoembryonic antigen plays a role in hepatic
      metastasis development.
AB  - We established a cell line with high metastatic potential to the liver (LS-LM4)
      after four successive repetitions of splenic injection of liver-metastatic cells
      in SCID mice. This cell line strongly expressed CEA and showed increased
      homotypic adhesion as compared with the parent cell line (LS174T). To examine the
      role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with
      anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay.
      Further, to study the role of CEA in the hepatic metastasis of cells with high
      metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the
      inhibition of hepatic metastasis after splenic injection in vivo was examined.
      There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated
      (100 microg/ml) LS-LM4 cells under a Ca2+-free condition as compared with the
      control (P<0.01). Anti-CEA antibody (100 microg/ml) inhibited cell aggregation
      under a Ca2+-free condition (P<0.05). Treatment with anti-E-cadherin antibody (60
      microg/ml) plus anti-CEA antibody (100 microg/ml) inhibited cell aggregation more
      potently than anti-E-cadherin antibody treatment alone in the presence of Ca2+.
      In vivo, there was a 75% decrease in the number of hepatic metastatic nodules in
      the G125 anti-CEA antibody-treated group as compared with the control group
      (P<0.01). Similarly, there was a 40% decrease in the diameter of metastatic
      nodules and there was a 90% decrease in total tumor volume of hepatic metastasis
      in the G125 anti-CEA antibody-treated group as compared with the control
      (P<0.01). These results suggest that increased metastatic potential to the liver
      is at least partly due to increased homotypic binding mediated by CEA.

PMID- 9548447
TI  - Effects of interleukin-12 on the induction of cytotoxic T lymphocytes from the
      regional lymph node lymphocytes of patients with lung adenocarcinoma.
AB  - Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated
      stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients
      with either autologous or HLA-A-locus-matched tumor cells. To investigate the
      effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL
      from HLA A24/adenocarcinoma patients with either autologous tumor cells or HLA
      A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of
      interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and
      populations of the lymphocyte subsets were examined. The addition of IL-12, or
      the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and
      the cytokine production (IFN-gamma, GM-CSF) of the CTL as compared with IL-2
      alone. The cytotoxic activity and cytokine production were both partially
      inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12
      had a higher proportion of CD3+/CD56+ cells than the CTL induced with IL-2 alone.
      The positively selected CD8+/CD56- lymphocytes showed PC-9-specific cytotoxic
      activity, because the population did not show any cytotoxicity to K562 or A549
      (HLA-A26/A30). However, the CD3+/CD56+ lymphocytes were cytotoxic to both PC-9
      and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the
      induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted
      cytotoxicity against tumor cells, and may be applicable for adoptive
      immunotherapy using CTL.

PMID- 9548446
TI  - Increased expression of sucrase and intestinal-type alkaline phosphatase in human
      gastric carcinomas with progression.
AB  - The activities of sucrase, total alkaline phosphatase (total ALP) and intestinal
      type alkaline phosphatase (I-ALP) were assayed in gastric carcinomas and in their
      surrounding mucosae from 57 patients with advanced cancers, and the localization
      of sucrase in 203 carcinomas, including 86 early cancers, was examined
      immunohistochemically using polyclonal anti-sucrase antibody. All three enzymes
      were active in the 57 carcinomas as well as in their surrounding mucosae, but the
      levels were fairly low as compared to those in normal jejunum mucosa. A
      considerable part of the total ALP activity in tumor specimens was assumed to be
      due to I-ALP itself. Increased sucrase and I-ALP were found with greater depth of
      invasion by undifferentiated-type carcinomas. The pattern of immunohistochemical
      localization of sucrase in the 203 carcinomas also clearly indicated increased
      expression with greater depth of invasion even in differentiated-type carcinomas.

PMID- 9548448
TI  - Suppression of anti-microtubule agent-induced apoptosis by nitric oxide: possible
      mechanism of a new drug resistance.
AB  - The propensity of a cell to undergo apoptosis has been proposed to be a
      determinant of sensitivity to anti-microtubule agents. The anti-microtubule
      agents vincristine and paclitaxel induce key features of apoptosis, such as
      intranucleosomal DNA fragmentation and changes in nuclear morphology in the human
      neuroblastoma cell line, NB-39-nu. Nitric oxide (NO) generated from NO-releasing
      drugs prevented anti-microtubule agent-induced apoptosis in this cell line. The
      mechanism of suppression of apoptosis by NO appears to be via the inhibition of
      an interleukin-1beta converting enzyme-like protease cascade. This finding
      reveals a new biological function of NO, as well as a new molecular insight into
      resistance to chemotherapy with anti-microtubule agents.

PMID- 9548449
TI  - Oral administration of a Kampo (Japanese herbal) medicine Juzen-taiho-to inhibits
      liver metastasis of colon 26-L5 carcinoma cells.
AB  - We have investigated the inhibitory effect of oral administration of Juzen-taiho
      to, a Kampo Japanese herbal medicine, on liver metastasis by the inoculation of a
      liver-metastatic variant (L5) of murine colon 26 carcinoma cells into the portal
      vein. Oral administration of Juzen-taiho-to for 7 days before tumor inoculation
      resulted in dose-dependent inhibition of liver tumor colonies and significant
      enhancement of survival rate as compared with the untreated control, without side
      effects. We also found that liver metastasis of L5 cells was enhanced in BALB/c
      mice pretreated with anti-asialo GM1 serum or 2-chloroadenosine, and in BALB/c
      nu/nu mice, compared to normal mice. This indicates that NK cells, macrophages,
      and T-cells play important roles in the prevention of metastasis of tumor cells.
      Juzen-taiho-to significantly inhibited the experimental liver metastasis of colon
      26-L5 cells in mice pretreated with anti-asialo GM1 serum and untreated normal
      mice, whereas it did not inhibit metastasis in 2-chloroadenosine-pretreated mice
      or T-cell-deficient nude mice. Oral administration of Juzen-taiho-to activated
      peritoneal exudate macrophages (PEM) to become cytostatic against the tumor
      cells. These results show that oral administration of Juzen-taiho-to inhibited
      liver metastasis of colon 26-L5 cells, possibly through a mechanism mediated by
      the activation of macrophages and/or T-cells in the host immune system. Thus,
      Juzen-taiho-to may be efficacious for the prevention of cancer metastasis.

PMID- 9548450
TI  - Absence of p53 overexpression and favorable response to cisplatin-based
      neoadjuvant chemotherapy in urothelial carcinomas.
AB  - It has been controversial whether cancer cells harboring loss or inactivation of
      the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents
      including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a
      negative regulator of p53, is assumed to be an alternative to p53 dysfunction.
      Archival urothelial carcinoma specimens obtained from 60 patients prior to
      cisplatin-based chemotherapy were immunohistochemically studied for
      overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with
      chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent
      chemotherapy for distant metastases or inoperable locoregional tumors. In group
      I, the responsiveness was correlated with staining status of p53 (P=0.0225) and
      the combination of p53 and mdm2 (P=0.0497). Negative staining of p53 and negative
      for both p53 and mdm2 could have predicted favorable response to chemotherapy in
      16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively. On the other hand,
      p53-positive and p53 and/or mdm2-positive staining could have predicted poor
      response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively.
      Disease-specific survival of the p53-negative group was significantly superior to
      that of the p53-positive group (P=0.0086). Difference in survival did not become
      more significant when overexpression of mdm2 was taken into consideration
      (P=0.0456). In contrast, in group II, there was no correlation of responsiveness
      to chemotherapy or survival with p53- or p53/mdm2-staining status. The patients
      with urothelial carcinomas negative for overexpression of p53 will benefit from
      neoadjuvant chemotherapy. From clinical viewpoint, however, p53 status alone or
      the combination of p53 and mdm2 status is not enough to identify those patients
      who will not benefit from the treatment.

PMID- 9548452
TI  - 1-Methyl-3-propyl-7-butylxanthine, a novel biochemical modulator, enhances
      therapeutic efficacy of adriamycin.
AB  - We have screened xanthine derivatives for activity as novel biochemical
      modulators by assay of their inhibitory effect on adriamycin efflux from tumor
      cells. Strong inhibition of adriamycin efflux was shown by some xanthine
      derivatives with various alkyl or oxoalkyl substituents at the 1-, 3- and 7
      positions. 1-Methyl-3-propyl-7-butylxanthine (XT-77), which had the greatest
      inhibitory effect on adriamycin efflux in vitro among the compounds tested,
      potentiated adriamycin-induced antitumor activity by causing an increase of
      adriamycin concentration in the tumor in vitro. Furthermore, XT-77 reduced the
      adverse drug reactions of adriamycin by decreasing the adriamycin concentrations
      in the heart and the liver. Thus, the combination of XT-77 with adriamycin not
      only increased the antitumor activity of adriamycin, but also decreased the
      adverse drug reactions.

PMID- 9548451
TI  - Role of MDM2 overexpression in doxorubicin resistance of breast carcinoma.
AB  - Several oncoproteins or tumor suppressor gene products have been indicated to be
      of value as predictors of the de novo resistance to cytotoxic agents. In this
      study, we have investigated the role of MDM2 (murine double minutes)
      overexpression in doxorubicin resistance of breast cancer. Immunocytochemical
      analysis demonstrated that MDM2-positive tumors, even with p53-negative
      phenotype, were significantly more resistant to doxorubicin treatment compared to
      MDM2-negative tumors. An in vitro experimental model using stable mdm2
      transfected MCF-7 cells carrying wild-type p53 confirmed that the cells become
      approximately 3-fold more resistant to doxorubicin as a result of MDM2
      overexpression, and the wild-type p53 function, such as the induction of p21Waf1
      following DNA damage, was significantly suppressed. MDM2 overexpression is
      suggested to be a novel marker for predicting lack of response to doxorubicin
      treatment in breast cancer patients.

PMID- 9548453
TI  - Calcitonin gene-related peptide is necessary for ultraviolet B-impaired induction
      of contact hypersensitivity.
AB  - Since nerve termini on Langerhans cells (LC) contain calcitonin gene-related
      peptide (CGRP), and since ultraviolet B radiation (UVR) causes CGRP to be
      released from cutaneous nerve endings, we examined whether CGRP participates in
      the immune aberrations caused in skin by UVR. First, intradermally injected CGRP,
      in a dose-dependent manner, reduced LC density and impaired CH induction when
      hapten was painted on the injected site. Second, CGRP antagonist restored CH
      induction after UVR. Third, anti-TNF-alpha Abs injected before CGRP prevented the
      loss of LC density and restored CH induction. Fourth, CGRP failed to impair CH
      induction in mast cell-deficient mice. Fifth, CGRP induced mast cells to release
      TNF-alpha. We conclude that CGRP plays an essential role in the loss of CH
      induction after UVR. These data indicate that UVR, by causing the release of CGRP
      from cutaneous nerve endings, triggers mast cell release of TNF-alpha, which
      impairs CH induction.

PMID- 9548454
TI  - Immunosuppressive effects of human CTLA4Ig in a non-human primate model of
      allogeneic pancreatic islet transplantation.
AB  - Ag-specific T cell activation requires a CD28-mediated costimulatory interaction.
      This observation has suggested novel approaches to suppress donor-specific
      immunity, including the use of soluble CD28 antagonists, such as CTLA4Ig, which
      suppresses transplant rejection in small animal models. In this study, CTLA4Ig
      therapy was examined in a non-human primate model of allogeneic pancreatic islet
      transplantation. Two of five CTLA4Ig-treated monkeys showed prolonged graft
      survival, which correlated with donor-specific hyporesponsiveness in vitro.
      Humoral responses to the transplanted tissue were suppressed in all treated
      animals. These results suggest that CTLA4Ig is effective in suppressing both
      humoral and cellular immune responses in a non-human primate model of allogeneic
      transplantation.

PMID- 9548455
TI  - A family of human lymphoid and myeloid Ig-like receptors, some of which bind to
      MHC class I molecules.
AB  - Leukocyte Ig-like receptors (LIRs) are a newly discovered family of
      immunoreceptors expressed on monocytes and B cells and at lower levels on
      dendritic cells and NK cells. The amino acid sequences in the extracellular
      regions of eight of these receptors show between 63 and 84% identity to the
      prototypic LIR-1 sequence. LIRs contain either two or four Ig domains and fall
      into three classes: those with cytoplasmic domains containing two, three, or four
      immunoreceptor tyrosine-based inhibitory motif-like motifs; those with a short
      cytoplasmic domain and no immunoreceptor tyrosine-based inhibitory motif-like
      motifs; and those with no transmembrane domain represented by a single LIR
      molecule that is presumably secreted. The LIRs are structurally related to the
      human Fc(alpha)R and the killer inhibitory receptors and map to the same region
      of chromosome 19 as these genes. Like killer inhibitory receptors, at least two
      LIRs bind to MHC class I Ags, but their different cellular distribution suggests
      a distinct role in immune system modulation.

PMID- 9548456
TI  - CD8+ T cells clear influenza virus by perforin or Fas-dependent processes.
AB  - Influenza virus infection is controlled in CD4-depleted mice that are also
      defective for the expression of either Fas (Fas-/-) or perforin (P-/-). Virus
      immune P+/+ and P-/- CD8+ T cells can thus function in, respectively, a Fas-/- or
      Fas+/+ lung environment. The obvious question is whether the P-/- CD8+ set is
      effective in Fas-/- mice, a conclusion that would tend to favor cytokine
      secretion as the mode of virus clearance. Short term chimeras were made with P-/-
      bone marrow, P+/+ or P-/- T cells, and Fas+/+ or Fas-/- irradiated recipients.
      While the P+/+ CD8+ population cleared the virus from Fas+/+ and Fas-/-
      respiratory epithelium, the P-/- effectors were operational only if there was the
      potential for Fas to be expressed on radiation-resistant lung cells. Target cell
      destruction mediated via the Fas or perforin pathways is clearly the primary
      mechanism used by CD8+ T cells to terminate this viral pneumonia.

PMID- 9548457
TI  - Molecular cloning of leukotactin-1: a novel human beta-chemokine, a
      chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist
      at CC chemokine receptors 1 and 3.
AB  - A new member of human beta-chemokine cDNA was isolated and named leukotactin-1
      (Lkn-1). Lkn-1, along with murine macrophage inflammatory protein-related protein
      1 and -2, defines a subgroup of beta-chemokines based on two conserved cysteines
      in addition to the four others conserved in all beta-chemokines. The putative
      mature Lkn-1 is composed of 92 amino acids with a calculated m.w. of 10,162. The
      Lkn-1 gene was mapped to human chromosome 17, region q12. Recombinant Lkn-1 was a
      potent chemoattractant for neutrophils, monocytes, and lymphocytes and induced
      calcium flux in these cells. Lkn-1 specifically induced calcium flux in CCR1- and
      CCR3-expressing HOS cell lines. Lkn-1 suppressed colony formation by human
      granulocyte-macrophage, erythroid, and multipotential progenitor cells stimulated
      by combinations of growth factors. Hence, we have isolated and characterized a
      human C6 beta-chemokine that is a potent agonist at CCR1 and CCR3 and shows broad
      biologic activities, including leukocyte chemoattraction.

PMID- 9548458
TI  - Constitutive activation of the Janus kinase-STAT pathway in T lymphoma
      overexpressing the Lck protein tyrosine kinase.
AB  - The Lck protein, a Src family tyrosine kinase, plays a critical role in T cell
      maturation and activation. Dysregulation of Lck expression or Lck kinase activity
      has been implicated in T cell leukemias from mice to humans, although the
      mechanism underlying Lck-mediated oncogenesis is still largely unclear. We report
      here that both DNA binding activities and tyrosine phosphorylation of STAT3 and
      STAT5, but not STAT1, are constitutively enhanced in the mouse T cell lymphoma
      LSTRA, which is a well-characterized cell line that overexpresses Lck protein and
      exhibits high levels of Lck kinase activity. Furthermore, Janus kinase 1 (jak1)
      and Jak2 protein tyrosine kinases are constantly activated in these cells, as
      determined by their autophosphorylation in an in vitro kinase assay and increased
      levels of tyrosine phosphorylation on immunoblots. Therefore, like Src
      transformed cells, Lck-overexpressing LSTRA cells also exhibit constitutive
      activation of distinct Jak and STAT proteins.

PMID- 9548459
TI  - Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen.
AB  - HLA-A*0201/Kb transgenic mice were immunized with oxidized mannan-mucin 1 (MUC1)
      as a fusion protein (containing five repeats of the 20-amino-acid MUC1 VNTR
      (variable number of tandem repeats) that generated highly active CD8+ CTLs to
      MUC1 peptides. In a direct CTL assay, the MUC1 peptides could be presented
      specifically by both the transgenic murine HLA-A*0201/Kb and human HLA-A*0201
      molecules. The 9-mer MUC1 peptide sequences (APDTRPA and STAPPAHGV) were
      presented by HLA-A*0201, although they did not contain L at P2 and L/V at P9, the
      preferred motifs; as a consequence, the binding was of relatively low affinity
      when compared with a high affinity-binding HIV peptide (ILKEPVHGV). In addition,
      when mice were immunized separately with the HLA-A*0201-binding peptides
      (STAPPAHGV or APDTRPAP-containing peptides-keyhole limpet hemocyanin-mannan),
      direct lysis of MCF-7 (HLA-A*0201+, MUC1+) also occurred. The findings are of
      interest for tumor immunotherapy, particularly as the CTLs generated to low
      affinity-binding peptides were highly active and could specifically lyse an HLA
      A*0201+ human breast cancer cell line without further in vitro stimulation. The
      findings demonstrate that the range of peptides that can generate CTLs is broader
      than formerly considered.

PMID- 9548460
TI  - The basis for self-tolerance of natural killer cells in beta2-microglobulin- and
      TAP-1- mice.
AB  - Cells from mice with mutations in the genes for beta2-microglobulin (beta2m) or
      for TAP-1 express only low levels of MHC class I proteins on their surfaces, and
      are thus sensitive to attack by normal NK cells. Although NK cells are present in
      beta2m- mice and TAP-1(-) mice, they are completely self-tolerant. The underlying
      mechanism for this tolerance is unknown. It has been proposed that education
      processes render NK cells from these mice hypersensitive to class I-mediated
      inhibition, so that they can be inhibited even by the low levels of class I
      expressed on autologous cells. In this study, we present evidence against this
      hypothesis, by demonstrating that NK cells from beta2m- mice and TAP-1(-) mice
      fail to attack beta2m(-)TAP-1(-) double-mutant cells in both in vitro and in vivo
      assays. The latter cells express substantially lower levels of class I than
      single-mutant cells, based on serologic tests, as well as a significantly
      diminished sensitivity to attack by class I-specific CTL. Furthermore, the Ly-49
      repertoire on NK cells derived from beta2m(-)TAP-1(-) mice is highly similar to
      that of either single mutant, indicating that the developmental processes that
      shape the Ly-49 repertoire cannot respond to the differences in class I levels
      among these mice. We propose that self-tolerance of NK cells in beta2m- mice and
      TAP-1(-) mice is likely to result from hyporesponsiveness of the cells to
      activating signals, or alternatively, to induction of inhibitory signaling
      through receptors specific for non-class I MHC ligands.

PMID- 9548461
TI  - Protein-tyrosine phosphorylation by IgG1 subclass CD38 monoclonal antibodies is
      mediated through stimulation of the FcgammaII receptors in human myeloid cell
      lines.
AB  - The human surface Ag CD38 is a 46-kDa type II transmembrane glycoprotein, and its
      expression is dependent on the cell differentiation and activation of
      lymphocytes. Our previous work in human myeloid cells showed that ligation of
      CD38 with mAbs (HB-7 and T-16; IgG1 subclass) not only induced protein-tyrosine
      phosphorylation but also potentiated superoxide generation stimulated by G
      protein-coupled receptors. In the present study we analyzed the mechanisms of
      action of the agonistic mAbs. HB-7-induced tyrosine phosphorylation could be
      still observed in human myeloid cells expressing CD38 mutants, of which
      cytoplasmic and transmembrane domains had been deleted or replaced by those of
      another type II glycoprotein (PC-1). Moreover, N-linked glycosylation on the cell
      surface CD38 was not required for the HB-7-induced cell signaling. The profile of
      tyrosine-phosphorylated proteins by HB-7 was exactly the same as that induced by
      cross-linking of FcgammaII receptors (FcgammaRII/CD32), and FcgammaRII itself was
      tyrosine phosphorylated in the two stimulated cells. The HB-7-induced tyrosine
      phosphorylation was completely abolished after masking of FcgammaRII with its
      mAb. Finally, F(ab')2 of HB-7 failed to mimic the actions of the whole form of
      mAb. These results indicate that anti-CD38 mAb-induced tyrosine phosphorylation
      and its associated cell response are entirely mediated through the FcgammaRII
      induced signaling pathway, possibly resulting from stimulation of the cell
      surface human FcgammaRII with the mouse Fc region (IgG1 subclass) of CD38-ligated
      mAbs.

PMID- 9548462
TI  - Spectratyping of TCRs expressed by CTL-infiltrating minor histocompatibility
      antigen-disparate allografts.
AB  - Minor histocompatibility Ags (HA) play prominent roles in stimulating allograft
      rejection and are recognized by CTLs that mediate this process. However, there is
      no information on the diversity of TCRs that are specific for single minor
      histocompatibility Ag peptides and expressed by CTLs in vivo. We have used the
      technique of spectratyping to study the diversity of Vbeta usage and beta
      complementarity-determining region 3 (CDR3) length of TCRs expressed by CTL
      infiltrating skin allografts expressing the immunogenic H4 peptide during the
      process of rejection. Spectratyping revealed overall reduction in diversity of
      both Vbeta usage and CDR3 length, with sequential application of primary, second
      set, and third-set H4-incompatible grafts. This dissection of the array of beta
      chains expressed by graft-infiltrating CTLs allowed the direct sequencing of
      individual beta-chain PCR products. Beta CDR3s were characterized by a net
      negative charge, as we have observed previously with CDR3s expressed by H4
      specific CTL clones selected in vitro. Identical and closely related CDR3 amino
      acid sequences could be identified that were shared by TCRs that 1) utilized
      different Vbeta genes, 2) derived from different mice, or 3) derived from
      different sequential sets of allografts on individual mice. Furthermore, a number
      of CDR3 sequences expressed by graft-infiltrating CTLs were identical or closely
      related to sequences we have identified previously in in vitro selected CTL
      clones that were specific for the H4 peptide.

PMID- 9548463
TI  - Apoptotic cell death upon contact of CD4+ T lymphocytes with HIV glycoprotein
      expressing cells is mediated by caspases but bypasses CD95 (Fas/Apo-1) and TNF
      receptor 1.
AB  - Loss of CD4+ T helper lymphocytes is central to the development of
      immunodeficiency after infection with HIV. In this study, we demonstrate that
      contact of primary uninfected CD4+ T lymphocytes with HIV-infected or HIV
      envelope glycoprotein-expressing cells results in apoptotic cell death of both
      uninfected and infected cells. Apoptosis was blocked by inhibitors of caspases/IL
      1beta-converting enzyme-like proteases. This finding provides conclusive evidence
      that cytotoxicity upon contact of HIV-infected and uninfected primary cells is an
      active process and represents another example for the role of caspases in the
      induction of apoptosis. Prevention of apoptosis by inhibition of caspases did not
      block the formation of syncytia, indicating that apoptosis occurs either in a
      subpopulation of cells or in syncytia. Cell death was not mediated by the CD95
      (Fas/Apo-1) or TNF receptor 1 molecules, which indicates a different pathway of
      apoptosis induction. The data indicate that initiation of apoptosis significantly
      shortens the life span of uninfected CD4+ T cells upon contact with HIV-infected
      cells and may represent a factor that contributes to the destruction of CD4+ T
      lymphocytes in vitro. Elucidation of the mechanism that initiates apoptosis in
      this situation will add to our understanding of both HIV pathogenesis and
      apoptotic signaling.

PMID- 9548464
TI  - A dominant-negative mutant of the Rab5 GTPase enhances T cell signaling by
      interfering with TCR down-modulation in transgenic mice.
AB  - TCR triggering results in the down-modulation of engaged receptors by
      endocytosis. As a result of this process, Ag-binding sites are depleted from the
      surface and signaling responses should be attenuated. To test the importance of
      TCR down-regulation on T cell signaling, we generated mice expressing a dominant
      negative form of Rab5 (Rab5N133I) in T cells. Rab5, a monomeric GTPase of the Ras
      superfamily, has been implicated in the regulation of early steps in the
      endocytic pathway. In Rab5N133I mice, mature thymocytes developed, but the
      absolute number of CD4+CD8+ double positive thymocytes was reduced. Fluid phase
      endocytosis was severely impaired in the transgenic thymocytes. In peripheral T
      cells, the kinetics and rate of ligand-induced TCR down-modulation were delayed
      and reduced. These effects were correlated with enhanced early and late signaling
      responses. Analysis of thymocyte development in doubly transgenic mice for
      Rab5N133I and a lymphocytic choriomeningitis virus (LCMV) peptide-specific TCR
      demonstrated that TCR signaling was enhanced by dominant inhibition of Rab5
      function, resulting in altered thymic selection. These findings suggest that TCR
      endocytosis is an important regulatory component of TCR signaling and that
      defects in this regulation can result in prolonged signaling and alter thymic
      development.

PMID- 9548465
TI  - Distinct signal transduction pathways mediate nuclear factor-kappaB induction by
      IL-1beta in epithelial and lymphoid cells.
AB  - We previously demonstrated that IL-1beta-mediated induction of the nuclear factor
      kappaB (NF-kappaB) transcription factor proceeds through the production of
      reactive oxygen intermediates in lymphoid cells, while it occurs independently of
      any oxidative stress in epithelial transformed cells. Indeed, inhibition of
      receptor internalization as well as NH4Cl and chloroquine blocked IL-1beta
      mediated induction of NF-kappaB in OVCAR-3 and in other epithelial cell lines but
      not in lymphoid cells, indicating that distinct pathways are involved.
      Conversely, while we observed phospholipase A2 activity in both cell types
      following IL-1beta stimulation, specific inhibitors of this enzyme inhibited NF
      kappaB induction only in lymphoid cells. Moreover, expression of the 5
      lipoxygenase (5-LOX) enzyme was not detected in epithelial cells, and inhibition
      of this enzyme blocked NF-kappaB induction by IL-1beta only in lymphoid cells.
      This study thus indicates that the activation of NF-kappaB following IL-1beta
      treatment involves the activation of phospholipase A2 and 5-LOX and the
      production of reactive oxygen intermediates (ROIs) in lymphoid cells, while in
      epithelial cells, another pathway predominates and could involve the acid
      sphingomyelinase. Moreover, arachidonic acid could induce NF-kappaB in epithelial
      and lymphoid cells, but this activation involved the 5-LOX enzyme and the
      production of ROIs only in lymphoid cells. The inefficiency of the ROI pathway in
      epithelial cells is probably the consequence of both low ROI production due to
      undetectable expression of 5-LOX and rapid degradation of hydrogen peroxide due
      to high catalase activity.

PMID- 9548466
TI  - oct-2 gene disruption eliminates the peritoneal B-1 lymphocyte lineage and
      attenuates B-2 cell maturation and function.
AB  - Targeted mutation of the gene for the Oct-2 transcription factor in mice caused
      neonatal lethality and abrogated mitogen-induced proliferation and
      differentiation of mature B lymphocytes in vitro. Here we show that Oct-2 is
      required for normal humoral responses upon immunization with T cell-dependent as
      well as T-independent Ags. oct-2-null T cell behavior was normal, implying a B
      cell-restricted lesion. oct-2-/- B cells displayed aberrant behavior during
      activation in vitro: both acquisition of markers of cellular activation and cell
      survival were diminished. Production of early B lineage cells in the bone marrow
      was normal, yet mature B cells were under-represented in blood and lymphoid
      organs. Furthermore, peritoneal B-1 lymphocytes were not detected in animals with
      a reconstituted oct-2-/- lymphoid system. We conclude that Oct-2 is required for
      B-1 cell maintenance and for normal Ag-driven maturation of conventional B cells
      in vivo.

PMID- 9548467
TI  - Role of Thy-1 in T cell development.
AB  - Tolerance to self proteins is accomplished in part by elimination of autoreactive
      immature T cells as they develop in the thymus. Although many investigators have
      studied the cellular interactions that regulate this important process, the
      specific molecules involved in negative selection are still not well understood.
      Thy-1 is a glycosyl-phosphatidylinositol-linked protein that is expressed at high
      levels on immature thymocytes, and recent evidence suggests that it is involved
      in thymocyte apoptosis. Correspondingly, we have found that Abs to Thy-1 block Ag
      dependent thymocyte deletion in an in vitro culture system. Thus, we investigated
      the role of Thy-1 in T cell development by using Thy-1 -deficient mice containing
      a TCR transgene specific for a class II MHC-restricted Ag. With this system, the
      role of Thy-1 in Ag-specific self-restriction and self-tolerance could be
      analyzed. Thy-1-null mice were found to undergo normal negative selection in
      three different models: the in vitro culture system, anti-CD3-induced thymocyte
      deletion in vivo, and Ag-induced thymocyte deletion in vivo. Self-restriction to
      MHC class II also appeared to occur normally in Thy-1-null mice. These results
      therefore suggest that Thy-1 is not essential for either self-restriction or self
      tolerance to MHC class II-restricted Ags. This finding is discussed in light of
      recent data regarding the role of other glycosyl-phosphatidylinositol-linked
      proteins in thymocyte development.

PMID- 9548468
TI  - Acquisition of granzyme B and Fas ligand proteins by human keratinocytes
      contributes to epidermal cell defense.
AB  - In vertebrate tissues, cell integrity is maintained by at least three mechanisms.
      During an immune response, injured cells are eliminated by cytotoxic lymphoid
      cells that produce perforin, granzyme B, and Fas ligand (FasL). Second,
      epithelial cells can produce FasL as an immunosuppressive protein, probably to
      protect the tissue against immune-mediated damage. Third, locally secreted
      antimicrobial peptides can be operative in the protection of animal and human
      epithelia. In this work, as another contribution to local mechanisms of host
      defense, the ability of human epidermal keratinocytes to produce cytotoxic
      proteins was investigated. To address this question, freshly isolated human
      epidermal cells and keratinocytes grown in vitro were studied. Freshly isolated
      epidermal cells did not express the cytolytic proteins. In contrast, keratinocyte
      growth to confluence was associated with granzyme B, perforin, and FasL mRNA and
      protein synthesis. These proteins were secreted in the culture medium. Further
      analysis showed that they were identical with the ones used by cytotoxic
      lymphocytes. Their function was then investigated with a view to a potential role
      in epidermal cell integrity. The data showed that activated human keratinocytes
      were able to protect against invading pathogens through granzyme B expression.
      This was demonstrated by the ability of granzyme B to greatly decrease the
      bacterial growth of Staphylococcus epidermidis. In addition, keratinocytes
      expressing FasL were found to prevent immune epidermal cell damage. Apoptosis of
      Fas-sensitive T cells occurred during coculture with confluent epidermal
      keratinocytes and was largely reduced by the addition of a FasL inhibitor. The
      data favor keratinocyte involvement in the regulation of dermal inflammatory
      responses.

PMID- 9548469
TI  - The mucosal adjuvanticity of cholera toxin involves enhancement of costimulatory
      activity by selective up-regulation of B7.2 expression.
AB  - Cholera toxin (CT) is a potent mucosal immunogen and adjuvant that can strongly
      prime mucosal T cells. The present study was undertaken to investigate the
      effects of CT on the expression and functional activity of the costimulatory
      molecules B7.1 and B7.2 on macrophages and the relationship of these effects to
      the mucosal adjuvanticity of CT. Bone marrow macrophages (BMM) were generated by
      culturing bone marrow with macrophage CSF or granulocyte-macrophage CSF. After
      treatment with either CT alone or IFN-gamma alone, B7.2 expression on BMM was
      moderately up-regulated and was further increased when BMM were treated with both
      CT and IFN-gamma together. Interestingly, CT had no effect on B7.1 expression
      despite the close relationship between these two molecules. Up-regulation of B7.2
      expression by CT was mediated by intracellular cAMP production, in that CT-B
      subunit had no effect and dibutyryl cAMP could mimic the effect. CT increased
      functional costimulatory activity of macrophages for both anti-CD3-stimulated and
      allostimulated T cells, an increase that was blocked by anti-B7.2, but not anti
      B7.1, Ab. B7.2 expression by Mac1+ Peyer's patch cells was increased after
      intraluminal exposure to CT in vivo. Treatment of mice with anti-B7.2 Ab in vivo
      inhibited both the mucosal adjuvanticity and the immunogenicity of CT. We
      conclude that CT enhances the costimulatory activity of mucosal APC by
      differentially up-regulating B7.2 expression, an effect that appears to be
      important for its mucosal adjuvanticity and immunogenicity.

PMID- 9548470
TI  - The p38 mitogen-activated protein kinase is activated by ligation of the T or B
      lymphocyte antigen receptors, Fas or CD40, but suppression of kinase activity
      does not inhibit apoptosis induced by antigen receptors.
AB  - We have investigated the activation of the p38 mitogen-activated protein kinase
      (MAPK) in normal mouse T and B cells and its role in apoptosis. Cross-linking of
      the CD3 chains of the TCR complex on proliferating T cells resulted in activation
      of p38 MAPK and MAPKAP kinase-2. Cross-linking of CD28 failed to activate p38
      MAPK or MAPKAP kinase-2, but synergized strongly with low doses of anti-CD3.
      Cross-linking of Fas on T cells also induced rapid activation of p38 MAPK and
      MAPKAP kinase-2. The in vivo activation of MAPKAP kinase-2 in response to cross
      linking of CD3, Fas, or CD3 and CD28 was shown to be dependent on p38 MAPK
      activity using a specific inhibitor, SB 203580. SB 203580 did not inhibit
      activation-induced cell death in T cells when used at concentrations that
      suppressed activation of MAPKAP kinase-2 in vivo. Cross-linking of the B cell Ag
      receptor (BCR) or CD40 on freshly isolated or LPS-activated splenic B cells or
      the immature B lymphoma, WEHI 231, resulted in activation of p38 MAPK and MAPKAP
      kinase-2. In vivo inhibition of p38 MAPK activity in WEHI 231 cells by SB 203580
      had no effect on either BCR-induced apoptosis or anti-CD40-mediated suppression
      of apoptosis. We conclude that the activation of p38 MAPK and MAPKAP kinase-2 by
      cross-linking of the TCR, BCR, Fas, or CD40 was not correlated with their roles
      in regulating lymphocyte survival, and that suppression of kinase activity did
      not inhibit the induction of apoptosis.

PMID- 9548471
TI  - Dissociation of cytokine signals for proliferation and apoptosis.
AB  - Cytokines such as IL-2 or IL-3 prevent cell death through apoptosis, either by
      preventing apoptosis directly or by sensitizing cells to survival factors present
      in serum. We demonstrate herein that BAF-B03 cells transfected with the wild-type
      IL-2R beta-chain undergo apoptosis when stimulated with IL-2 or IL-3 in the
      absence of serum. IL-2 also induced apoptosis in normal IL-2-responsive human T
      cell blasts in the absence of serum, and furthermore, epidermal growth factor and
      fibroblast growth factor induced increased rates of apoptosis in fibroblasts in
      the absence of serum, suggesting that cytokine-induced apoptosis in the absence
      of serum survival factors might represent an important biologic phenomenon. In
      the presence or the absence of serum, IL-2 and IL-3 induced expression of both c
      Myc and Bax. In contrast, optimal cytokine-induced expression of Bcl-2 requires
      serum. Constitutive expression of Bcl-2 prevented cytokine-induced apoptosis.
      Transferrin mimicked serum by inducing an increase in Bcl-2 expression levels and
      concurrently prevented apoptosis. These results suggest that the balance between
      cytokine- and serum-induced Bcl-2 expression and cytokine-induced Bax expression
      may determine whether a cell undergoes cytokine-induced apoptosis. In BAF/BO3
      cells expressing a mutant IL-2Rbeta with a deletion of the acidic domain, IL-2
      did not induce either Bax expression or apoptosis. This suggests that the acidic
      domain of the IL-2R beta-chain plays an essential role in regulating IL-2
      mediated Bax expression and apoptosis. Cytokine-induced apoptosis and its
      counterbalance by survival factors present in serum may play an important role in
      the regulation of cellular homeostasis during pathophysiologic processes.

PMID- 9548472
TI  - Insulin down-regulates the inducible nitric oxide synthase pathway: nitric oxide
      as cause and effect of diabetes?
AB  - Evidence in this paper indicates that insulin can down-regulate the inducible
      nitric oxide synthase (iNOS) pathway in vivo. The iNOS pathway is up-regulated in
      diabetes-prone rats and mice and is associated with an autoimmune process.
      However, the results presented here indicate that macrophage nitric oxide (NO)
      production and iNOS mRNA expression are also elevated in rats or mice made
      diabetic by streptozotocin injection in which there is no primary autoimmune
      component. Insulin administration reduces NO production in autoimmune-prone and
      streptozotocin-induced diabetic rodents. Finally, insulin decreases macrophage NO
      production in normal hosts. These results indicate that the autoimmune paradigm
      is inadequate to explain increased NO in diabetes. As a potential mechanism to
      explain insulin-mediated regulation of NO production, TGF-1 may be involved
      because 1) macrophages from diabetic mice produce less TGF-beta1 than macrophages
      from normal hosts; 2) the circulating TGF-beta1 level is lower in diabetic mice;
      and 3) insulin administration increases circulating TGF-beta1 in normal mice.
      Together, these results provide evidence that increased NO in diabetes is not
      only a cause but also an effect of beta-cell destruction and results in part from
      a heretofore unrecognized immunomodulatory activity of insulin.

PMID- 9548473
TI  - Functional consequences of dysregulated B7-1 (CD80) and B7-2 (CD86) expression in
      B or T lymphocytes of transgenic mice.
AB  - T cell activation and tolerance are regulated by interactions between CD28 or
      CTLA-4 on T cells and B7 costimulatory molecules on APCs. We have generated
      transgenic mouse strains that constitutively express B7-1 (CD80) at high levels
      on B cells or T cells or express B7-2 (CD86) on T lymphocytes to examine the
      consequences of dysregulated B7 expression on T cell responses. The transgene
      derived B7 molecules are functional, because B7-1 transgenic B cells are more
      efficient APCs than are wild-type B cells, and the activation of B7 transgenic T
      cells is less dependent on exogenous costimulation than that of wild-type T
      cells. In vivo, constitutive expression of B7 molecules leads to the elimination
      of immature B cells. The expression of B7 molecules on thymocytes results in the
      down-regulation of CD28 expression. However, B7 transgenic mice have normal
      numbers of mature lymphocytes and mount normal T cell responses following
      immunization with protein Ag. Neither anergy induction nor superantigen-mediated
      deletion of T cells is altered by the dysregulated expression of B7-1 or B7-2 on
      B or T lymphocytes in these transgenic strains. Therefore, functionally
      significant levels of B7 expressed constitutively on mature lymphocytes are not,
      by themselves, sufficient to abrogate T cell tolerance or induce autoimmune
      disease.

PMID- 9548474
TI  - T cell stimulation via CD47: agonistic and antagonistic effects of CD47
      monoclonal antibody 1/1A4.
AB  - CD47/integrin-associated protein has been extensively studied on various cell
      types. The function of CD47 on T cells, however, remained poorly understood. We
      demonstrate here that our CD47 mAb 1/1A4 has both inhibitory as well as
      costimulatory effects in terms of T cell activation. Soluble, not cross-linked,
      CD47 mAb 1/1A4 blocks allogeneic MLRs. This effect is predominantly observed with
      suboptimal numbers of stimulator cells. In contrast, cross-linking of CD47 in the
      presence of CD28 mAb or phorbol ester induces vigorous T cell proliferation that
      is sensitive to cyclosporin A. Cross-linking, but not immobilization, of the CD47
      mAb 1/1A4 is an essential requirement for the CD28- or phorbol ester-dependent
      induction of T cell mitogenesis. Furthermore, CD47 mAb 1/1A4 induces T cell
      proliferation when coimmobilized with a CD3 mAb to the same surface. Ligation
      with cross-linked 1/1A4 mAb induces an increase in intracellular free calcium
      levels and leads to tyrosine phosphorylation of various cellular proteins and, in
      the presence of suboptimal concentrations of plate-bound CD3 mAb, to enhanced IL
      2 promotor activity in T cells. Furthermore, we present evidence that upon cross
      linking of CD47 with mAb 1/1A4, purified T cells acquire responsiveness for
      several T cell growth factors. IL-1beta and/or IL-6 dramatically augment this
      CD47-induced cytokine responsiveness. Our results suggest that the novel
      activation pathway via CD47 might be critically involved in Ag-dependent and Ag
      independent T cell functions.

PMID- 9548475
TI  - Structural requirements for beta1 integrin-mediated tyrosine phosphorylation in
      human T cells.
AB  - The beta1 integrin adhesion receptors activate signal transduction pathways that
      induce tyrosine phosphorylation of a variety of substrates. Increased tyrosine
      phosphorylation is mediated by the beta1 subunit cytoplasmic domain, which
      consists of 46 amino acids and contains no intrinsic kinase activity. In the H9 T
      cell line, beta1 integrin engagement leads to the increased tyrosine
      phosphorylation of three 105 to 115-kDa substrates that are distinct from focal
      adhesion kinase (FAK): HEF1 (human enhancer of filamentation 1), a protein with
      structural homology to p130Cas, and two novel substrates, pp105 and pp115. DNA
      mediated gene transfer was used to explore the role of the beta1 cytoplasmic
      domain in integrin-mediated tyrosine phosphorylation of HEF1, pp105, and pp115 in
      human T cells. Using a chimeric receptor composed of the cytoplasmic domain of
      the beta1 integrin subunit and the extracellular and transmembrane domains of the
      CD2 Ag, we demonstrate that the beta1 cytoplasmic domain is necessary and
      sufficient for inducing tyrosine phosphorylation of each of these three
      substrates in H9 T cells. Analysis of a series of beta1 cytoplasmic domain
      truncations reveals that a truncation of only five amino acids from the carboxyl
      terminal end of the beta1 cytoplasmic domain abrogates the ability of the
      CD2/beta1 chimera to activate tyrosine phosphorylation of HEF1, pp105, or pp115.
      Thus, the carboxyl-terminal five amino acids, Lys-Tyr-Glu-Gly-Lys (KYEGK), of the
      beta1 integrin cytoplasmic domain are critical for the coordinate tyrosine
      phosphorylation of three non-FAK substrates in human T cells.

PMID- 9548476
TI  - TAP peptide transporter-independent presentation of heat-killed Sendai virus
      antigen on MHC class I molecules by splenic antigen-presenting cells.
AB  - Immunization of C57BL/6 (B6) mice with heat-killed Sendai virus generates a
      Sendai virus-specific CD8+ T cell response. This suggests that APC have the
      capacity to take up and present exogenous (nonreplicative) Sendai virus Ag on MHC
      class I molecules. Little is known about the intracellular requirements for
      processing of this form of Ag and its presentation on MHC class I. Therefore, we
      have studied the processing and presentation of heat-killed Sendai virus Ag on
      MHC class I molecules in splenic APC. Heat-killed Sendai virus Ags were
      efficiently processed by normal B6 as well as by TAP-1(-/-) splenic APC.
      Presentation was MHC class I restricted, since no presentation was seen by APC
      from TAP-1/beta2m-/- mice that lack expression of MHC class I. Presentation
      occurred even in the presence of brefeldin A, but was blocked by cytochalasin D
      as well as chloroquine. Finally, B6 as well as TAP-1(-/-) splenic APC, loaded
      with heat-killed Sendai virus Ag in vitro, primed naive CD8+ T cells in vivo.
      These studies suggest the existence of a TAP-independent pathway for Ag
      presentation on MHC class I in normal splenic APC, bearing many similarities with
      the MHC class II pathway for Ag presentation. The present results are discussed
      in relation to the events underlying the processing and presentation of exogenous
      Ag on MHC class I, the molecular basis for CD8+ T cell priming during viral
      infections, and prospects for vaccine development.

PMID- 9548477
TI  - Identification of two distinct populations of dendritic cells in afferent lymph
      that vary in their ability to stimulate T cells.
AB  - Immunofluorescent staining and flow cytometric analysis of dendritic cells from
      cattle afferent lymph has established that within the afferent lymph veiled cells
      (ALVC) there are two phenotypically distinct, major populations. One is CD11a+,
      CD5+, CD21- and expresses the bovine WC10 (workshop cluster 10) molecule and the
      Ag recognized by mAb CC81 but is not recognized by mAbs CC149 and IL-A24. The
      second ALVC subpopulation is CD11a-, CD5-, CD21+/-, workshop cluster 10- and is
      not recognized by mAb CC81 but is recognized by mAb CC149. Thus, the two
      populations, which can be identified by staining for CD11a, are defined by the
      differential expression of a number of Ag. The ALVC populations had differing
      capacities to stimulate T cells. CD11a- ALVC were more effective at stimulating
      proliferative responses in allogeneic CD4+ T cells and CD8+ T cells. This was not
      related to binding of CTLA4Ig or CD40L fusion proteins, implying similar levels
      of expression of their ligands, CD80 and CD86 or CD40. Both subsets were able to
      present OVA to resting memory CD4+ T cells, indicating that both were able to
      take up and process soluble native protein. In contrast, the CD11a- ALVC were
      more effective in presenting respiratory syncytial virus Ag to resting CD4+ T
      cells. Considering the central role of dendritic cells in the initiation of
      immune responses in naive animals, the two cell types may have different roles in
      the induction of primary responses induced following infection or immunization.

PMID- 9548478
TI  - Natural variants of the immunodominant HLA A11-restricted CTL epitope of the EBV
      nuclear antigen-4 are nonimmunogenic due to intracellular dissociation from MHC
      class I:peptide complexes.
AB  - EBV isolates from human populations with a high frequency of HLA A11 evade
      recognition by CTLs specific for an immunodominant A11-restricted epitope derived
      from the EBV nuclear antigen 4 (EBNA-4). We have previously described four
      nonimmunogenic variants of this epitope carrying single amino acid substitutions
      in the anchor residues of the peptide. We have now investigated the antigenicity,
      A11 binding capacity, endoplasmic reticulum translocation, endogenous processing,
      and presentation of these variants. The nonimmunogenic peptides were either
      unable to bind to HLA A11 or formed complexes of significantly lower stability
      compared with the immunogenic epitope. The latter peptides were produced in
      relatively large amounts by endogenous processing of EBNA-4 and associated with
      A11 molecules almost as efficiently as the immunogenic epitope, but the complexes
      failed to accumulate at the cell surface. The defect was not reversed by
      incubation of lymphoblastoid cell lines carrying the variant EBV strains at 26
      degrees C. CTL lysis of HLA A11 positive targets was achieved by expressing one
      of the nonimmunogenic peptides through a vaccinia recombinant. However, the
      amount of peptide required for CTL sensitization exceeded, by at least 30-fold,
      that required for recognition of the immunogenic epitope. Collectively, these
      results suggest that complexes containing the nonimmunogenic peptides are formed
      but are then destroyed intracellularly. Thus, a specialized sorting mechanism
      seems to contribute in shaping the repertoire of peptides presented to T
      lymphocytes.

PMID- 9548479
TI  - Processing of engulfed apoptotic bodies yields T cell epitopes.
AB  - Programmed death via apoptosis is the metazoan physiologic mode of cell death.
      Apoptotic cells are recognized by scavenger phagocytes via a number of membrane
      receptors and engulfed. Thereafter, little is known of their fate, or that of
      phagocytes. Here, we have traced apoptotic cells upon their engulfment by
      macrophages. After 3 h, apoptotic cells were contained in discrete well-defined
      vacuoles. Upon overnight chase, several small vesicles, possibly originating from
      the fragmentation of original vacuoles, were evident all over the macrophage
      body. Furthermore, Ags were diffused in the cytosol of some cells, which raises
      the possibility that epitopes from engulfed apoptotic cells may associate with
      macrophage MHC class I molecules and be recognized by T lymphocytes. Indeed, Ag
      specific CTLs recognize and specifically lyse syngeneic macrophages upon
      phagocytosis of MHC class I-positive or -negative apoptotic cells, provided that
      they contain the relevant Ags. Synthesis and membrane expression of class I
      molecules by macrophages, together with functional transporters associated with
      Ag presentation, were necessary for recognition and lysis. The indirect
      presentation of epitopes from engulfed apoptotic cells by scavenger Ag-presenting
      phagocytes may, in the absence of "danger" signals, have implications for the
      establishment of central and peripheral self-tolerance.

PMID- 9548480
TI  - Leech immunocytes contain proopiomelanocortin: nitric oxide mediates hemolymph
      proopiomelanocortin processing.
AB  - This report establishes the presence of mammalian-like proopiomelanocotropic
      hormone (POMC), and six of its peptides, including adrenocorticotropic hormone
      (ACTH) and melanocyte-stimulating hormone (MSH), in the immune tissues of the
      leech Theromyzon tessulatum. The 25.4-kDa protein was purified by high pressure
      gel permeation chromatography, anti-ACTH-affinity column, and reverse-phase HPLC.
      Its characterization was performed by Edman degradation, enzymatic treatments,
      and electrospray mass spectrometry. Leech POMC exhibits considerable amino acid
      sequence similarity to mammalian POMC. Of the six peptides, three showed high
      sequence similarity to their vertebrate counterparts met-enkephalin, alpha-MSH,
      and ACTH: 100, 84.6, and 70%, respectively; whereas gamma-MSH, beta-endorphin,
      and gamma-lipotropin hormone exhibited only 45, 20, and 10% sequence identity,
      respectively. No dibasic amino acid residues were found at the C terminus of the
      gamma- and beta-MSH peptides. In contrast, the leech alpha-MSH was flanked at its
      C-terminal by the Gly-Arg-Lys amidation signal. ACTH and corticotropin-like
      intermediary pituitary peptide were also C-terminally flanked by dibasic amino
      acid residues. The coding region of leech POMC was obtained by reverse
      transcription-PCR using degenerated oligonucleotide primers. Circulating levels
      of ACTH and MSH were 10 and 1 fmol/microl hemolymph, respectively. Morphine, in a
      dose-dependent manner, increased the levels of both peptides threefold; this
      effect was blocked by naloxone treatment. Similar results were found with the
      anandamide. Leech ACTH was processed to MSH by the enzymes neutral endopeptidase
      (24.11) and angiotensin-converting enzyme. Leech alpha-MSH had the same activity
      as authentic alpha-MSH in two bioasssay systems. Taken together, the study
      demonstrates that POMC is present in invertebrates and its immunoregulatory
      actions have been conserved during evolution.

PMID- 9548481
TI  - Evidence for multiple promoters of the human IL-5 receptor alpha subunit gene: a
      novel 6-base pair element determines cell-specific promoter function.
AB  - In addition to a previously characterized promoter (P1), we now show the
      existence of a second promoter for the human IL-5Ralpha gene. Initially, a
      genomic region (P2) 5' upstream of human IL-5Ralpha exon 2 was cloned by an
      inverted PCR. The transcriptional start site was then mapped to a deoxycytidine
      (C) residue within P2 by analyzing cellular mRNA with both the 5' rapid
      amplification of cDNA end-PCR and S1 nuclease protection assays. Transfection of
      eosinophilic HL-60 cells with reporter gene constructs in which either P1 or P2
      was linked to the bacterial chloramphenicol acetyltransferase (CAT) gene resulted
      in CAT expression; little or no CAT expression occurred in other myeloid and
      nonmyeloid cell lines. Deletion studies showed that a 66-bp region, ranging from 
      31 to +35, was sufficient to promote CAT expression in eosinophilic HL-60 cells.
      Analysis of linker-scanning mutants identified a novel 6-bp element (5' CTAATT
      3') spanning -19 to -14 that was essential for P2 promoter activity. In
      electrophoretic mobility shift assays, a P2 region from -31 to +1 containing the
      unique 6-bp element, when used as a probe, formed a complex with a protein(s)
      that was found only in the eosinophilic cell line. This binding activity was lost
      upon replacement of the 6-bp element with a 6-bp linker, suggesting that this
      element likely serves as the binding site for an eosinophilic HL-60 cell-specific
      transcription factor(s). Together, these data suggest an important role for P2
      promoter in the regulation of eosinophil-specific expression of the human IL-5
      receptor alpha gene.

PMID- 9548482
TI  - Molecular analysis of V gene sequences encoding cytotoxic anti-streptococcal/anti
      myosin monoclonal antibody 36.2.2 that recognizes the heart cell surface protein
      laminin.
AB  - Anti-streptococcal/anti-myosin mAb 36.2.2 is unique among the cross-reactive anti
      streptococcal mAbs due to its cytotoxicity for rat heart cells and its ability to
      strongly label the surface of heart cells in indirect immunofluorescence assays.
      In this study, cytotoxic mAb 36.2.2 was found to react strongly with the
      extracellular matrix protein laminin in immunoblots and inhibition assays, while
      11 other cross-reactive anti-streptococcal mAbs did not react with laminin and
      were not cytotoxic. Cytotoxicity appeared to correlate with the presence of
      laminin on the surface of cells. Heavy and light chain variable region genes
      encoding mAb 36.2.2 were highly homologous to other V genes encoding anti
      carbohydrate and/or autoantibodies. VH, JH, and Jkappa segments of mAb 36.2.2 may
      be encoded by germline gene segments. The VH segment may be identical with an as
      yet unidentified VH7183 family germline sequence, and the 36.2.2 Vkappa region
      gene is encoded by a Vkappa8 family member.

PMID- 9548483
TI  - Delta-opioid receptors expressed by Jurkat T cells enhance IL-2 secretion by
      increasing AP-1 complexes and activity of the NF-AT/AP-1-binding promoter
      element.
AB  - Recent molecular evidence points to transient and/or stage-specific expression of
      delta- and kappa-opioid receptors by thymic and peripheral T lymphocytes. Since
      medical treatments or stress commonly increase opioid levels, it is important to
      understand the mechanisms by which opioids affect T lymphocyte functions. We
      therefore created and studied a T cell line expressing the cloned delta-opioid
      receptor (DOR1). DOR1 ligation by a specific DOR1 agonist, deltorphin, augmented
      IL-2 secretion by synergizing with signals from TCR-CD3 and CD28. Reporter gene
      constructs were used to map this effect of deltorphin to the AP-1- and NF-AT/AP-1
      binding sites of the IL-2 promoter. Although DOR1 signaling increased [Ca2+]i,
      deltorphin enhanced transcriptional activity of the NF-AT/AP-1-binding site via a
      mechanism independent of calcineurin and distinct from the effects of elevated
      [Ca2+]i. Deltorphin also increased accumulation of AP-1 transcription factor
      complexes, suggesting that DOR1 augments IL-2 secretion by increasing the AP-1
      component of the NF-AT/AP-1 transcription factor. These results advance the
      molecular understanding of opioid effects on lymphocytes, and in addition,
      demonstrate regulation of IL-2 synthesis and secretion by the novel mechanism of
      receptor-mediated AP-1 induction.

PMID- 9548484
TI  - Cloning and analysis of the promoter region of CCR5, a coreceptor for HIV-1
      entry.
AB  - The chemokine receptor CCR5 is a cofactor for cellular entry of macrophage-tropic
      strains of HIV-1. Expression of CCR5 is restricted to T cells, macrophages, and
      certain cell lines; however, the mechanisms controlling its expression remain
      largely unknown. To delineate these mechanisms, approximately 1.0 kb of DNA from
      the immediate 5' upstream region of CCR5 was cloned and characterized. CCR5
      promoter activity was up-regulated by PMA, and a region spanning -417 to +61
      relative to the transcription start site was sufficient for the basal and induced
      activity. DNase I footprinting assays demonstrated several protected areas within
      this region, and gel shift assays determined binding sites for transcriptional
      factors Oct-1, Oct-2, T cell factor 1alpha, and GATA1. CCR5 promoter activity was
      also induced by IL-2 or anti-CD3 Ab, while stimulation with anti-CD28 Ab markedly
      reduced CD3-mediated up-regulation of the CCR5 promoter. Flow cytometry confirmed
      the findings at the level of cell surface expression. Further delineation of the
      regulation of the CCR5 promoter will be important for a more comprehensive
      understanding of the pathogenesis of HIV disease.

PMID- 9548485
TI  - Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of
      NF-kappaB-mediated transcription.
AB  - The NF-kappaB family of transcription factors regulates the inducible expression
      of a variety of genes. Recently, we showed that elevation of intracellular cyclic
      AMP inhibits NF-kappaB-mediated transcription in human monocytes and endothelial
      cells without preventing nuclear translocation of NF-kappaB complexes. The
      present study examined the molecular mechanism of this inhibition. We
      hypothesized that activation of the protein kinase A signaling pathway may
      inhibit NF-kappaB-mediated transcription by phosphorylating proteins, such as
      cAMP response element-binding protein (CREB), which compete for limiting amounts
      of the coactivator CBP. Here, we show that the amino-terminal region (amino acids
      1-450) of CBP specifically interacts with the carboxyl-terminal region (amino
      acids 286-551) of NF-kappaB p65 (RelA) both in vitro and in vivo. Functional
      studies using human endothelial cells demonstrated that overexpression of CBP
      rescued cAMP inhibition of NF-kappaB-mediated transcription and transcription
      mediated by a chimeric protein, GAL4-p65(286-551), which contained the GAL4 DNA
      binding domain fused to the carboxyl-terminal region of p65 (amino acids 286
      551). In contrast, overexpression of CREB inhibited GAL4-p65(286-551)-mediated
      transcription. These results suggest that activation of the protein kinase A
      pathway inhibits NF-kappaB transcription by phosphorylating CREB, which competes
      with p65 for limiting amounts of CBP.

PMID- 9548486
TI  - The DMB promoter: delineation, in vivo footprint, trans-activation, and trans
      dominant suppression.
AB  - The HLA-DM loci encode the heterodimeric unconventional class II MHC molecules
      that are coexpressed with conventional class II MHC molecules. DM molecules are
      essential for the proper formation and function of conventional class II MHC
      molecules. This report characterizes the DMB promoter both by in vivo footprint
      and by in vitro functional analysis and reveals a promoter structure similar to
      that of conventional class II MHC genes. DR-negative mutant cell lines
      selectively defective in the transcription factor or class II trans-activator
      (CIITA) were used to reveal a requirement for both these factors in DMB promoter
      activation. Complementation of defective cell lines with the appropriate
      transcription factor reconstituted DMB promoter activation. Further analysis with
      CIITA identified several mutant forms of CIITA that are trans-dominant-negative
      mutants, i.e., they suppressed DMB promoter activation by transfected and
      endogenous CIITA. These mutants may be used in abiological setting to down
      regulate the function of DM in Ag processing.

PMID- 9548487
TI  - IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription
      in mouse macrophages.
AB  - IL-4 suppresses the IFN-gamma-induced expression of the IFN regulatory factor-1
      (IRF-1) gene, and this suppression is attenuated by increasing the amount of IFN
      gamma. The effects of IFN-gamma and IL-4 on transcription of a reporter gene
      under control of a 1.3-kb fragment from the IRF-1 gene promoter or the STAT
      binding element (SBE) from this gene in the context of a heterologous promoter
      are similar to their effects on the endogenous IRF-1 gene. IFN-gamma-dependent
      transcription of reporter gene is suppressed by IL-4, but IL-4 alone has no trans
      activating function. IL-4 treatment does not inhibit the tyrosine phosphorylation
      or nuclear translocation of IFN-gamma-activated STAT1. Rather, IFN-gamma and IL-4
      independently activate STAT1 and STAT6, respectively, and both proteins bind to
      the IRF-1 SBE in homodimeric form. The affinity of STAT1 for the IRF-1 SBE is
      higher than the affinity of STAT6, as measured by competition with unlabeled
      oligonucleotide. These observations suggest that IL-4 may suppress IFN-gamma
      stimulated transcription of the IRF-1 gene by activation of STAT6, which can
      compete with STAT1 for occupancy of the IRF-1 SBE when STAT1 levels are low.
      Suppression may be attenuated as the quantity of STAT1 relative to that of STAT6
      increases in cells treated with increasing amounts of IFN-gamma and displaces
      STAT6.

PMID- 9548488
TI  - Augmentation of dendritic cells in murine organ donors by Flt3 ligand alters the
      balance between transplant tolerance and immunity.
AB  - Treatment of mice with the recently cloned hemopoietic growth factor Flt3 ligand
      (FL; 10 microg/day for 10 days) resulted in a large increase in myeloid lineage
      cells within the liver. While the number of nonparenchymal cells (NPC) harvested
      from liver increased about 9-fold, a 90-fold increase was observed in the
      proportion of CD11c+ dendritic cells (DC) recovered from NPC following overnight
      (18-h) culture in granulocyte-macrophage CSF. In contrast, only a 50% increase
      was seen in CD11c+ cells within heart single cell suspensions and in the number
      of DC obtained from hearts after 18-h culture. Liver NPC and heart cell
      suspensions freshly isolated from 10-day FL-treated animals exhibited increased T
      cell allostimulatory capacity compared with controls. Overnight cultured DC from
      livers of FL-treated animals expressed both higher levels of costimulatory
      molecules (CD80 and CD86) and allostimulatory activity than those from controls.
      Heart-derived DC also displayed enhanced stimulatory capacity. Pretreatment of
      organ donors with FL for either 5 or 10 days before transplant of organs to
      normal recipients abrogated the spontaneous liver allograft acceptance normally
      observed and resulted in delayed or acute graft rejection (median survival times,
      40 and 12 days, respectively). Heart rejection was significantly accelerated by
      pretreatment of donors with FL for 5 or 10 days (median survival times, 8 and 7
      days, respectively, vs 12 days in controls). These novel findings reveal the
      potent immunologic adjuvant properties of FL in vivo. They also show that
      substantial augmentation of the number of potential allostimulatory cells in
      donor organs before transplantation favors rejection rather than tolerance
      induction.

PMID- 9548489
TI  - Transcriptional regulation of the complement receptor 2 gene: role of a
      heterogeneous nuclear ribonucleoprotein.
AB  - Complement receptor 2 (CR2) has been implicated as a regulator of B cell
      function. In this study, we sought to identify mechanisms that control the
      expression of the CR2 gene in human B cells. Dibutyryl cAMP increased the DNA
      binding activity of a nuclear protein that recognized specifically a CR2 promoter
      defined oligonucleotide in human B cell lines. The nuclear protein was
      subsequently purified from B cell nuclear extracts using a biotinylated CR2
      promoter-defined oligonucleotide. Partial amino acid sequence analysis of
      internal peptides revealed that the 42-kDa protein belongs to a family of
      heterogeneous nuclear ribonucleoproteins (hnRNP). Using a set of mutated double
      stranded oligonucleotides, we demonstrated that the purified protein displayed
      sequence specificity for the CR2 promoter-defined oligonucleotide. Like some
      hnRNP, this protein was found to bind to single-stranded DNA. The DNA-binding
      activity of the purified protein increased after in vitro phosphorylation with
      protein kinase A. Using a CAT reporter gene driven by a single recognition site
      in B cell lines, dibutyryl cAMP caused a 3-fold induction of reporter gene
      expression. The highest induction (6.7-fold) was achieved with a combination of
      dibutyryl cAMP and PMA. The involvement of the nuclear protein in regulating the
      expression of the CR2 gene is supported by our finding that dibutyryl cAMP
      increased the levels of the CR2 mRNA and CR2 surface membrane protein in human B
      cell lines. These data strongly suggest that a cAMP-inducible hnRNP, which can
      recognize a novel DNA-motif, controls the expression of the CR2 gene.

PMID- 9548490
TI  - Differential induction of DNA-binding activities following CD19 cross-linking in
      human B lineage cells.
AB  - The B cell-specific cell surface molecule CD19 is expressed at all stages of B
      cell development, including normal plasma cells, and mediates signal transduction
      via interaction with cytoplasmic effector proteins. Cross-linking CD19 on early
      human B lineage cells induces the formation of a CD19/Vav/phosphatidylinositol-3
      kinase complex, tyrosine phosphorylation of CD19 and Vav, and activation of the
      Ras pathway. To further explore the ramifications of CD19 signaling, the current
      study examined whether phosphorylation of Elk-1, activation of activator protein
      1 (AP-1), or activation of nuclear factor-kappaB (NF-kappaB) transcription
      factors occurred following CD19 cross-linking. The cells used were the BLIN-1 pre
      B cell line expressing low levels of cell surface mu heavy chain associated with
      surrogate light chain and the 1E8 immature B cell line expressing cell surface
      mu/kappa. Lysates from CD19 cross-linked 1E8 cells induced robust phosphorylation
      of an Elk-1 fusion protein in vitro, whereas no phosphorylation of Elk-1 fusion
      protein occurred using lysates from CD19 cross-linked BLIN-1 cells. An
      electrophoretic mobility shift assay employing AP-1 and NF-kappaB consensus
      oligonucleotides was used to demonstrate that AP-1 -binding activity increased,
      while constitutive NF-kappaB-binding activity was not enhanced, following 2 h of
      CD19 cross-linking in 1E8 cells. Supershift experiments revealed that JunD and c
      Fos proteins mediated anti-CD19 induced AP-1-binding activity in 1E8 cells. In
      contrast, CD19 cross-linking in BLIN-1 cells resulted in the induction of NF
      kappaB, but had no apparent effect on AP-1-binding activity. These data suggest
      that CD19-mediated signal transduction activates different transcription factors
      at juxtaposed stages of B cell development that may culminate in the activation
      or suppression of distinct sets of genes.

PMID- 9548491
TI  - Adoptive transfer of in vitro-targeted, activated T lymphocytes results in total
      tumor regression.
AB  - Adoptive immunotherapy of cancer uses the transfer of tumor-reactive immune
      cells. The success of this procedure is dependent upon the specificity of the
      transferred immune cells, their number, and their ability to reach their target
      cells. We genetically modified T lymphocytes and equipped them with the ability
      to specifically recognize tumor cells. Tumor cells overexpressing the ErbB-2
      receptor served as a model. The target cell recognition specificity is conferred
      to T lymphocytes by transduction of a chimeric gene encoding the zeta-chain of
      the TCR and a single chain antibody (scFv(FRP5)) directed against the human ErbB
      2 receptor. The chimeric scFv(FRP5)-zeta gene was introduced into primary mouse T
      lymphocytes via retroviral gene transfer. Naive T lymphocytes were activated and
      infected by cocultivation with a retrovirus-producing packaging cell line. The
      scFv(FRP5)-zeta fusion gene was expressed in >75% of the T cells. These T cells
      lysed ErbB-2-expressing target cells in vitro with high specificity. We tested
      the antitumor efficacy of scFv(FRP5)-zeta-expressing T cells in a syngeneic
      BALB/c model. The mice were treated with autologous, transduced T cells. The
      adoptively transferred scFv(FRP5)-zeta-expressing T cells caused total regression
      of ErbB-2-expressing tumors. The presence of the transduced T lymphocytes in the
      tumor tissue was monitored. No humoral response directed against the transduced T
      cells was observed. Abs directed against the ErbB-2 receptor were detected upon
      tumor lysis.

PMID- 9548492
TI  - TCR vaccines for active immunotherapy of T cell malignancies.
AB  - We have developed a TCR-based vaccine approach for the treatment of T cell
      malignancies. TCR genes were isolated from C6VL, a T cell tumor of C57BL/Ka
      origin. The transmembrane encoding domains of the TCR genes were replaced by
      sequences encoding for phosphatidylinositol-linked cell surface expression. A
      high expressing cell line was produced by transfection and amplification of the
      TCR genes. Large quantities of soluble native C6VL TCR-alphabeta protein was
      obtained by treating the high-expressing cells with a specific phospholipase and
      purifying the released TCR by affinity chromatography. Following vaccination with
      the TCR linked to keyhole limpet hemocyanin, specific anti-TCR humoral responses
      were induced. Both the carrier protein and an adjuvant were required for optimal
      responses. Hyperimmune serum from vaccinated mice reacted specifically with C6VL
      cells, and the immunizations did not affect the TCR repertoire, which suggested
      that the immune response was Id specific. The TCR-vaccinated mice were
      specifically protected from a lethal number of C6VL tumor cells. B cell-deficient
      mice were not protected by TCR vaccinations. Similarly, TCR-immunized mice
      depleted of CD8+ cells prior to tumor challenge were not protected. Thus, C6VL
      TCR vaccine effectively stimulated tumor protection, which depends on the
      presence of both B cells and CD8+ T cells.

PMID- 9548493
TI  - IL-18 protects mice against pulmonary and disseminated infection with
      Cryptococcus neoformans by inducing IFN-gamma production.
AB  - We examined the effects of a newly identified cytokine, IL-18, originally
      designated as IFN-gamma-inducing factor, in a mouse model of pulmonary and
      disseminated infection with a highly virulent strain of Cryptococcus neoformans.
      Administration of murine rIL-18 enhanced elimination of live micro-organisms from
      the lungs, prevented fungal dissemination to the brain, reduced the level of
      serum cryptococcal capsular polysaccharide Ags, and increased the survival rate
      of infected mice. Histologic examination of lung sections of infected and PBS
      treated mice showed a poor cellular inflammatory reaction and a large number of
      multiplying C. neoformans yeast cells in alveolar spaces. In contrast, massive
      infiltration of inflammatory cells, consisting mainly of mononuclear cells,
      characterized sections of lungs of infected animals treated with IL-18. Treatment
      with IL-18 also increased the level of serum IFN-gamma. In addition, the
      protective effect of IL-18 on cryptococcal infection was abrogated by
      administration of neutralizing anti-IFN-gamma mAb. Finally, we examined the
      effect of neutralizing anti-IL-18 Ab on cryptococcal infection to define the
      physiologic role of this cytokine in host defense using another weakly virulent
      strain of C. neoformans, which induced the expression of IL-18 mRNA in the
      infected lungs. Administration of this Ab exacerbated the infection, as shown by
      the increased lung burden. Our results indicate that IL-18 plays an important
      role in host defense against infection with C. neoformans.

PMID- 9548494
TI  - A cryptic T cell epitope on the apical membrane antigen 1 of Plasmodium chabaudi
      adami can prime for an anamnestic antibody response: implications for malaria
      vaccine design.
AB  - We have investigated the proliferative and Th cell responses to the Plasmodium
      chabaudi adami DS homologue of the Plasmodium falciparum apical membrane Ag 1
      (AMA-1), a leading malaria vaccine candidate. Immunodominant T cell epitopes were
      defined following immunization of BALB/c mice with Escherichia coli-expressed,
      refolded P. c. adami DS AMA-1 recombinant protein and testing cells from the
      draining lymph nodes for responses against a series of overlapping peptides
      spanning P. c. adami AMA-1. A limited number of major T cell sites were
      identified in both conserved and variable regions of the protein. Several cryptic
      epitopes that evoked T cell responses following immunization with peptides, but
      not after protein immunization, were also identified. Adoptive transfer of a T
      cell line specific for a conserved cryptic epitope (corresponding to residues 31
      50) provided help for an anti-AMA-1 protein-specific Ab response following in
      vivo challenge with P. c. adami parasitized RBC, such that AMA-1-specific Abs
      appeared more rapidly in recipient mice than in controls. Furthermore, T cells
      specific for cryptic epitopes afforded partial protection against P. c. adami
      infection in nude mice. The identification of conserved cryptic Th cell epitopes
      has important implications for malaria vaccine design.

PMID- 9548495
TI  - Targeting of cytotoxic T cells against leukemic B cells by bispecific antibody
      (aCD3 x aCD19) does not distract the T cell from its primary target.
AB  - Bispecific Abs (BsAb) represent a novel format of immunotherapy, recognizing
      immune effector cells (e.g., T cells), on the one hand, and target cells (e.g.,
      tumor cells), on the other hand. To be successful, cross-linking of the two cell
      types is necessary for effector cell activation and subsequent killing of the
      malignant target cells. We asked the question, whether CTL that were incubated
      with the BsAb aCD3 x aCD19 and malignant B cells and activated to kill the
      malignant B cells were still able to eliminate their natural target cells (e.g.,
      virus-infected autologous body cells). To test this, HLA-A*0201-restricted,
      influenza-specific CTL were incubated with BsAb- and HLA-A*0201-positive B
      lymphoid tumor cells in combination with HLA-A*0201-positive, virus-infected non
      B lymphoid cells as natural target cells. The results showed that even in the
      presence of BsAb and high amounts of tumor B cells, CTL were still capable of
      eliminating the virus-infected non-B lymphoid target cells; actually, CTL
      recognized and eliminated the homologous original target cells preferentially.

PMID- 9548496
TI  - Involvement of mitogen-activated protein kinase pathways in the nuclear responses
      and cytokine production induced by Salmonella typhimurium in cultured intestinal
      epithelial cells.
AB  - Central to the pathogenesis of Salmonella typhimurium is its ability to engage
      the host cell in a two-way biochemical interaction. As a consequence of this
      interaction, a dedicated protein secretion system, termed type III, is activated
      in these bacteria and directs the translocation of signaling proteins into the
      host cell. Secretion of these proteins stimulates host cell signal transduction
      pathways that lead to a variety of cellular responses. An important feature of S.
      typhimurium pathogenesis is the induction of a profound inflammatory response in
      the intestinal epithelium. In this report, we show that S. typhimurium induces
      host cell signal transduction pathways that lead to the activation of the
      transcription factors NF-kappaB and AP-1, resulting in the production of
      proinflammatory cytokines such as IL-8. We also show that S. typhimurium
      infection of cultured intestinal epithelial cells results in the activation of
      the mitogen-activated protein (MAP) kinases ERK, JNK, and p38. Induction of these
      signaling pathways and the synthesis of IL-8 was strictly dependent on the
      function of the invasion-associated type III protein secretion system encoded by
      S. typhimurium. Pretreatment of cells with the highly specific p38 MAP kinase
      inhibitor SB 203580 prevented S. typhimurium-induced IL-8 production. These
      results indicate that the inflammatory response induced by S. typhimurium may be
      due to the specific stimulation of MAP kinase signaling pathways leading to
      nuclear responses.

PMID- 9548497
TI  - Functional properties of human intestinal mast cells cultured in a new culture
      system: enhancement of IgE receptor-dependent mediator release and response to
      stem cell factor.
AB  - Culture of human mast cells (MC) in vitro has only been possible to date in the
      presence of 3T3 fibroblasts. The aim of the present study was to maintain freshly
      isolated human MC in culture without addition of feeder cells and to study their
      functional properties. We isolated cell suspensions containing 1 to 11% MC from
      human intestinal tissue and cultured them in standard medium. MC survived in
      culture for about 2 wk without cytokine supplementation and for several months
      with supplementation of medium with stem cell factor (SCF). SCF selectively
      supported MC survival, whereas the number of contaminating cells declined rapidly
      during culture. Most interestingly, we found that histamine and leukotriene
      release induced by IgE receptor cross-linking was substantially enhanced in
      cultured MC compared with that in MC stimulated directly after cell isolation.
      Cultured MC, but not freshly isolated MC, released mediators in response to SCF
      in a concentration-dependent fashion provided that the cells were cultured in SCF
      free medium. These findings demonstrate that human MC isolated from intestinal
      tissue can be maintained in culture in vitro for several weeks. After culture
      they have different functional properties, which might resemble more closely the
      functional status of human intestinal MC in vivo than that of freshly isolated
      cells.

PMID- 9548498
TI  - Beta2 integrins are not required for tyrosine phosphorylation of paxillin in
      human neutrophils.
AB  - Although many of the receptors mediating neutrophil (polymorphonuclear leukocyte
      (PMN)) adhesion to extracellular matrix (ECM) proteins have been identified, the
      signal transduction pathways leading to cell spreading are not clearly defined.
      Studies showing that protein tyrosine phosphorylation increases with PMN adhesion
      suggest that phosphorylation is critical for adhesion-dependent processes. In
      other cells, increased tyrosine phosphorylation of focal adhesion kinase (FAK)
      and paxillin are thought to play pivotal roles in ECM-mediated signaling. In the
      present study we compared the tyrosine phosphorylation of FAK and paxillin in
      PMNs plated onto thrombospondin (TSP) or laminin (LN). Increased tyrosine
      phosphorylation of paxillin correlated with adhesion and spreading of PMNs plated
      onto LN or TSP. In PMNs adherent to LN, the kinetics of FAK phosphorylation
      preceded the kinetics of paxillin phosphorylation, suggesting that paxillin may
      be a downstream target of FAK. In contrast, FAK was not phosphorylated in PMNs
      spread on TSP. These findings suggested activation of different signaling
      pathways in TSP- vs LN-adherent PMNs. Others have proposed that paxillin
      phosphorylation requires beta2 integrins. Therefore, we used PMNs from a patient
      with leukocyte adhesion deficiency (LAD), lacking beta2 integrins, to determine
      whether these receptors were necessary for paxillin phosphorylation. LAD PMNs did
      not adhere to LN, and consequently, there was no tyrosine phosphorylation of FAK
      or paxillin. In contrast, paxillin, but not FAK, was phosphorylated in LAD PMNs
      adherent and spread on TSP. These results indicate that ECM-beta2 integrin
      mediated signaling initiates the FAK/paxillin signaling pathway(s), while TSP
      mediated signaling results in paxillin phosphorylation independent of FAK
      phosphorylation.

PMID- 9548499
TI  - Characterization of the CCR2 chemokine receptor: functional CCR2 receptor
      expression in B cells.
AB  - We have derived anti-human CCR2-specific mAbs by immunization with synthetic
      peptides corresponding to CCR2 sequences presumably involved in the interaction
      with its ligand(s). The characterization of these mAbs includes the ability to
      recognize the CCR2 receptor specifically, as well as the function based on their
      ability to promote Ca2+ influx or to block MCP-1-induced Ca2+ influx and
      chemotaxis. One mAb (MCP-1 R02) that is directed to the NH2 terminal domain of
      the CCR2 receptor has MCP-1 agonist activity, and two that recognize the third
      extracellular domain (MCP-1R04 and MCP-1 R05) have MCP-1 antagonist activity. We
      analyzed the presence of CCR2 in several PBL and tonsil-derived leukocyte
      populations and found expression of this receptor in monocytes, activated T
      cells, and, surprisingly, in B cells. CCR2 receptor expression in B cells was
      further corroborated in Southern blot using CCR2-specific probes. Moreover, both
      MCP-1 and the agonist mAb trigger specific B cell migration via a PTX-sensitive
      mechanism, indicating the presence of a functional CCR2 receptor in these cells.

PMID- 9548500
TI  - Alteration of the cytokine phenotype in an experimental lung granuloma model by
      inhibiting nitric oxide.
AB  - Pulmonary granulomatous inflammation modulated by IFN-gamma and IL-12 is also
      associated with augmented inducible nitric oxide synthase (NOS II). To address
      the role of increased nitric oxide synthesis in this model, mice received daily
      i.p. injections of NG-nitro-L-arginine-methyl ester (L-NAME; 8 mg/kg) during both
      the 2-wk immunization period with purified protein-derivative (PPD) and the
      subsequent lung challenge with PPD-coated Sepharose beads. Other groups of
      animals received saline, L-NAME or NG-nitro-D-arginine-methyl ester (D-NAME; 8
      mg/kg) during the pulmonary embolization period and not the PPD sensitization
      period. On day 4 post-PPD bead challenge, PCR analysis of the whole lung revealed
      that NOS II expression appeared to be similar in both of the L-NAME treatment
      protocols. L-NAME-treated mice in both dosing protocols had lung lesions that
      were significantly larger than granuloma lesions measured in mice that received
      saline or D-NAME. The enlarged lesions from L-NAME-treated mice contained
      markedly greater numbers of neutrophils and eosinophils. Equivalent numbers of
      PPD-activated dispersed cells from whole lungs of L-NAME-treated mice produced
      significantly higher levels of IL-4 and IL-10 and smaller amounts of IL-12 and
      IFN-gamma compared with similar lung cultures derived from control or D-NAME
      treated mice. Levels of C-C chemokines such as monocyte chemoattractant protein-1
      (MCP-1), C10, and macrophage inflammatory protein-1alpha (MIP-1alpha) were also
      significantly elevated in lung cultures from L-NAME-treated mice compared with
      controls. Thus, nitric oxide regulates the size and cellular composition of the
      Th1-type lung granuloma, possibly through its effects on the cytokine and
      chemokine profile associated with this lesion.

PMID- 9548501
TI  - C1q augments platelet activation in response to aggregated Ig.
AB  - Immune complexes and aggregated IgG (agg-IgG) induce platelet aggregation and the
      release reaction. Immune complexes also activate the complement system and
      interact with the complement component C1q. Since platelets possess both Fc and
      C1q receptors capable of signal transduction, the present study focused on the
      interaction between these binding sites and platelet activation. Subaggregating
      doses of agg-IgG (20-400 microg/ml) were identified for washed platelets from
      each of 11 healthy donors, and platelet aggregation was monitored in the presence
      or the absence of increasing concentrations of C1q (5-100 microg/ml). C1q
      produced a dose-dependent potentiation of platelet alphaIIb/beta3 integrin
      activation, platelet aggregation, and granule secretion when combined with low
      doses of agg-IgG. C1q alone was without effect. Maximal enhancement of agg-IgG
      induced platelet activation was noted at C1q concentrations ranging from 50 to
      100 microg/ml. The observed C1q-induced potentiation of platelet aggregation in
      response to agg-IgG was blocked by polyclonal antibody F(ab')2 directed against
      platelet binding sites recognizing the collagen-like domain of C1q (cC1qR) or by
      mAb Fab (IV.3) directed against platelet FcgammaRII receptors. These data suggest
      a cooperative interaction between platelet FcgammaRII and cC1q receptors and
      support a potential role for platelet cC1q receptors in pathologic platelet
      activation by circulating immune complexes often associated with in vivo
      thrombosis and thrombocytopenia.

PMID- 9548502
TI  - Interchangeable endotoxin-binding domains in proteins with opposite
      lipopolysaccharide-dependent activities.
AB  - Host defense against microorganisms involves proteins that bind specifically to
      bacterial endotoxins (LPS), causing different cellular effects. Although LPS
      binding protein (LBP) can enhance LPS activities, while bactericidal/permeability
      increasing protein (BPI) and Limulus anti-LPS factor (LALF) neutralize LPS, it
      has been proposed that their LPS-binding domains possess a similar structure.
      Here, we provide evidence that the LBP/LPS-binding domain is, as in the LALF
      structure, solvent exposed and therefore available for LPS binding. Our
      investigations into the activity of LPS-binding domains of different LPS-binding
      proteins, in the context of LBP, provide the first functional analysis of these
      domains in a whole protein. We constructed domain exchange hybrid proteins by
      substituting 12 amino acids of the LBP/LPS-binding domain with those of BPI and
      LALF and expressed them in Chinese hamster ovary cells. Although discrete point
      mutations within the LPS-binding domain of LBP disrupted its specific functions,
      the hybrid proteins were still able to bind LPS and, in addition, retained the
      wild-type LBP activity of enhancing LPS priming for FMLP-induced oxygen radical
      production by neutrophils and transferring LPS aggregates to CD14. Although BPI
      and LALF display opposite activities to LBP, and LALF does not share any sequence
      homology with LBP, our data provide strong evidence that LBP, BPI, and LALF
      possess a solvent-exposed, interchangeable LPS binding motif that is functionally
      independent of LPS transport or neutralization.

PMID- 9548503
TI  - Human alternative complement pathway-mediated lysis of rabbit erythrocytes is
      enhanced by natural anti-Galalpha1-3Gal antibodies.
AB  - Human serum is effective at lysing unsensitized rabbit erythrocytes due to
      activation of the alternative complement pathway. Hemolysis is known to be
      enhanced by the addition of human IgG. We demonstrate that the enhancement of
      alternative pathway-mediated rabbit E lysis by human Ig is due to natural Abs
      specific for galactosyl (Gal)alpha1-3Gal. Depletion of normal human serum (NHS)
      of anti-Galalpha1-3Gal Abs removes almost all hemolytic activity from NHS, and
      activity can be restored by repletion with anti-Galalpha1-3Gal affinity-purified
      Abs. Factor B-depleted serum (inactive alternative pathway) did not lyse rabbit
      erythrocytes. Although C2-depleted serum was fully hemolytic, activity was
      removed by depletion of anti-Galalpha1-3Gal Abs. Of the total anti-Galalpha1-3Gal
      Abs affinity isolated from NHS, about one-third were IgM and two-thirds were IgG.
      Both anti-Galalpha1-3Gal IgG and IgM enhanced alternative pathway-mediated
      erythrocyte lysis.

PMID- 9548504
TI  - Aberrant cytokine expression and autocrine regulation characterize macrophages
      from young MRL+/+ and NZB/W F1 lupus-prone mice.
AB  - We investigated whether macrophages (Mphi) from young, lupus-prone MRL+/+ and
      NZB/W F1 mice expressed common defects in immunoregulatory cytokine production.
      Endotoxin-activated Mphi from both strains, obtained well before disease signs,
      had a markedly reduced capacity to maintain IL-1 production compared with Mphi
      from normal strains (BALB/c, A/J, and C57BL/6). Mphi from lupus-prone mice showed
      similar defects in IL-6 and TNF-alpha production, which preceded the IL-1 defect.
      In fact, defective TNF-alpha production appeared to be responsible for aberrant
      expression of the other cytokines because this defect was the first to be
      expressed, and treatment with exogenous TNF-alpha reduced the extent of defective
      IL-1 and IL-6. These "proinflammatory" cytokine defects appeared to be selective
      because the anti-inflammatory cytokine IL-10 was not expressed aberrantly in the
      lupus-prone strains. For this reason, and because anti-IL-10 mAb treatment did
      not correct defective proinflammatory cytokine production, IL-10 did not appear
      to be responsible for these defects. IFN-gamma was able to normalize TNF-alpha
      production in Mphi from lupus-prone mice, demonstrating a stimulus-specific
      induction of the proinflammatory defects. These studies also revealed that Mphi
      from the three normal strains studied here maintain a precise inverse
      relationship between levels of TNF-alpha and IL-10, a relationship not seen in
      Mphi from lupus-prone strains. These findings reveal shared elements of cytokine
      dysregulation in the two principal animal models of multigenic lupus, and suggest
      that the study of Mphi (and perhaps other cells of the innate immune system) may
      provide valuable insights into intrinsic functional defects associated with
      systemic autoimmunity.

PMID- 9548505
TI  - Thrombin activates nuclear factor-kappaB and potentiates endothelial cell
      activation by TNF.
AB  - Thrombin is the central bioregulatory enzyme in hemostasis and is generated in
      vascular beds in which inflammatory responses are ongoing. In this study, we
      examined the effect of thrombin, both alone and in combination with TNF, on gene
      expression in porcine aortic endothelial cells (EC). Thrombin (1-10 U/ml) induced
      increased mRNA levels of E-selectin, monocyte chemoattractant protein-1, IL-8,
      plasminogen activator inhibitor-1, and IkappaB-alpha. These effects were mimicked
      by a thrombin receptor-activating peptide; preincubation of thrombin with hirudin
      blocked the induction of mRNA, suggesting that the increased gene expression was
      due to thrombin-specific activity. Because these genes are known to contain
      nuclear-factor-kappaB (NF-kappaB)-binding elements in their promoter region, we
      next examined the ability of thrombin to activate this transcription factor. As
      detected by electrophoretic mobility shift assay, thrombin (10 U/ml) or thrombin
      receptor-activating peptide (100 microM) stimulated increased NF-kappaB-binding
      activity. Supershift analysis revealed that these complexes were comprised
      principally of the RelA (p65) and NF-kappaB1 (p50) Rel family members. Thrombin
      alone did not substantively increase protein levels of E-selectin despite the
      increase in E-selectin mRNA levels. However, thrombin (3-10 U/ml) stimulated a 10
      fold enhancement in the ability of TNF (0.3-1.0 ng/ml) to induce E-selectin
      surface expression. Similar potentiation of TNF-induced NF-kappaB activity and E
      selectin transcription by thrombin was observed in experiments utilizing
      luciferase reporter constructs expressed in bovine aortic EC. The ability of
      thrombin to potentiate TNF-induced EC activation thus provides an important
      mechanism by which products of the coagulation cascade may enhance cytokine
      mediated inflammatory responses.

PMID- 9548506
TI  - Generation of HER-2/neu-specific cytotoxic neutrophils in vivo: efficient arming
      of neutrophils by combined administration of granulocyte colony-stimulating
      factor and Fcgamma receptor I bispecific antibodies.
AB  - Abs are able to induce inflammatory antitumor responses by recruiting IgG Fc
      receptor (FcgammaR)-bearing cytotoxic effector cells. We recently described the
      capacity of the high affinity FcgammaRI (CD64) to trigger cytotoxic activity of
      neutrophils (PMN) during granulocyte CSF (G-CSF) treatment. To take advantage of
      FcgammaRI as a cytotoxic trigger molecule on PMN, two Ab constructs were
      prepared. We show that a chimeric human IgG1 Ab (Ch520C9) and an anti-FcgammaRI
      bispecific Ab (BsAb; 22x520C9), both directed to the proto-oncogene product HER
      2/neu, interact with FcgammaRI. In addition, both Ab constructs mediate enhanced
      lysis of HER-2/neu-expressing tumor cells by G-CSF-primed PMN. However,
      engagement of FcgammaRI by Ch520C9 was inhibited by human serum IgG, thereby
      abrogating the enhanced Ch520C9-mediated cytotoxicity. BsAb 22x520C9, which binds
      FcgammaRI outside the ligand binding domain, effectively recruits the cytotoxic
      potential of FcgammaRI on G-CSF-primed PMN regardless of the presence of human
      serum. These results indicate that under physiologic conditions, serum IgG
      impairs activation of FcgammaRI-mediated cytotoxicity by conventional antitumor
      Abs. The IgG blockade can be circumvented with anti-FcgammaRI BsAbs. Using human
      FcgammaRI transgenic mice we demonstrate that BsAb 22x520C9 is able to engage
      FcgammaRI in vivo. BsAb 22x520C9 injected i.v. was readily detected on
      circulating PMN of G-CSF-treated transgenic animals. In addition, we showed that
      PMN remain "armed" with BsAb 22x520C9 during migration to inflammatory sites, and
      that after isolation such PMN specifically lyse HER-2/neu-expressing tumor cells.
      These results point to the possibility of targeting anti-FcgammaRI BsAbs to G-CSF
      primed PMN in vivo, endowing them with specific anti-tumor activity.

PMID- 9548507
TI  - CD40 ligand stimulates proinflammatory cytokine production by human endothelial
      cells.
AB  - Functional expression of CD40 has recently been described on the surface of
      HUVEC, and activation of these cells with CD40 ligand (CD40-L) leads to increased
      adhesion molecule expression. Here, we analyzed the effect of CD40 triggering on
      cytokine production by HUVEC. CD40-L-transfected fibroblasts, in contrast to
      their untransfected counterparts, as well as a soluble recombinant human CD40
      L/murine CD8alpha chimeric molecule were able to importantly increase (by a mean
      of fourfold) the production of leukemia inhibitory factor (LIF) by HUVEC. CD40-L
      displayed an additive effect with IL-4, IL-1alpha, and TNF-alpha on the
      enhancement of LIF secretion. Cyclosporin A did not affect LIF synthesis by
      resting or CD40-L-activated HUVEC, whereas dexamethasone diminished the basal
      level of LIF production and abrogated the CD40-L effect. The secretions of two
      other proinflammatory cytokines, granulocyte-macrophage CSF and IL-6, were also
      increased in the presence of CD40-L. However, CD40-L neither affected HUVEC
      proliferation nor rescued them from IFN-gamma- and TNF-alpha induced apoptosis.
      Together, these results indicate that endothelial cell activation by CD40-L may
      play an important role not only in leukocyte recruitment through enhancement of
      adhesion molecule expression, but also in the maintenance of an inflammatory loop
      through the increase in proinflammatory cytokine secretion.

PMID- 9548508
TI  - Oncostatin M stimulates the expression and release of the IL-6 receptor in human
      hepatoma HepG2 cells.
AB  - Soluble IL-6R (sIL-6R), which lacks the transmembrane domain, has been suggested
      to be a potent immunomodulator of IL-6 biologic activity. In this study, the
      ability of cells of hepatic origin to generate the sIL-6R was investigated. It
      was found that oncostatin M alone or in combination with the glucocorticoid
      analogue dexamethasone significantly up-regulated IL-6R release. Oncostatin M
      appeared to generate the sIL-6R primarily through an alternative splicing
      mechanism. Since sIL-6R is able to form biologically active complexes with IL-6,
      the release of the sIL-6R from hepatocytes may be important to sensitize cells
      lacking the membrane-bound receptor, particularly during an acute phase reaction.

PMID- 9548509
TI  - Human monocytes and macrophages express substance P and neurokinin-1 receptor.
AB  - We present data demonstrating the gene expression of substance P and its receptor
      in human peripheral blood-isolated monocytes and macrophages. Using the RT-PCR
      assay, preprotachykinin-A (substance P) mRNA is detected in human peripheral
      blood-isolated monocytes and macrophages. Among the alpha, beta, and gamma
      transcripts of the substance P gene, only the beta and gamma transcripts are
      detectable in these cells. By Southern blot assay these RT-PCR-amplified
      transcripts are recognized using a specific substance P probe. Sequence analysis
      of the RT-PCR products from both monocytes and macrophages also confirmed the
      structure of these transcripts, which are identical to those found in human
      neuronal cells. At the protein level, both human monocytes and macrophages
      produced endogenous substance P as determined by an enzyme immunoassay.
      Capsaicin, a vanillyl fatty acid amide (ingredient of hot pepper), released
      substance P from both human monocytes and macrophages. In addition, using nested
      RT-PCR analysis, we identified the presence of mRNA for neurokinin-1 receptor
      (the receptor for substance P) in human peripheral blood-isolated monocytes and
      macrophages, which was confirmed by DNA sequencing analysis. The demonstration
      that human monocytes and macrophages express substance P and its receptor support
      the notion that substance P is biologically involved in regulating the functions
      of these cells in an autocrine fashion.

PMID- 9548510
TI  - IL-11 regulates macrophage effector function through the inhibition of nuclear
      factor-kappaB.
AB  - Recombinant human IL-11 (rhIL-11) is an anti-inflammatory cytokine that can
      reduce the production of inflammatory mediators such as TNF-alpha, IL-1beta, IL
      12, IL-6, and nitric oxide. Inhibition of proinflammatory cytokine production
      from activated macrophages was associated with a reduction in the levels of LPS
      induced TNF-alpha, IL-1beta, IL-6, and IL-12 p40 mRNA. Analysis of rhIL-11
      effects on transcription factors that activate proinflammatory cytokines
      demonstrated that the level of LPS-induced NF-kappaB binding activity in the
      nucleus of rhIL-11-treated peritoneal macrophages was significantly reduced. The
      block to NF-kappaB nuclear translocation correlated with the ability of rhIL-11
      to maintain or increase protein levels of the inhibitors of NF-kappaB, IkappaB
      alpha, and IkappaB-beta following LPS treatment. Furthermore, rhIL-11-treatment
      of LPS macrophages resulted in significant elevation of IkappaB-alpha and IkappaB
      beta mRNA levels. These results suggest that the anti-inflammatory activity of
      rhIL-11 is mediated in part by inhibition of NF-kappaB-dependent transcriptional
      activation. Furthermore, these studies demonstrate for the first time the
      regulation of IkappaB-beta by an anti-inflammatory cytokine. Given the finding
      that inappropriate activation of NF-kappaB contributes to multiple inflammatory
      conditions, the ability of rhIL-11 to inhibit the binding activity of this
      pleiotropic transcription factor indicates that rhIL-11 has therapeutic potential
      in a wide range of diseases.

PMID- 9548511
TI  - Identification of a new mouse beta-chemokine, thymus-derived chemotactic agent 4,
      with activity on T lymphocytes and mesangial cells.
AB  - Thymus-derived chemotactic agent 4 (TCA4), a new member of the beta-chemokine
      family, was cloned from a mouse thymic cDNA library. High levels of TCA4 mRNA are
      expressed in thymus; lower levels of message are found in spleen, heart, and
      kidney. Anti-TCA4 antibodies were used to localize sites of TCA4 expression
      within lymphoid tissues. In the thymus, UEA-1+ medullary epithelial cells, some
      endothelial cells, and additional undefined stromal elements were stained with
      anti-TCA4. TCA4 was also expressed as a meshlike network in splenic white pulp
      and in the medullary region of the lymph nodes. In addition, some lymph node and
      splenic blood vessels stained with anti-TCA4 antibodies. Rel B NFkappaB-deficient
      mice lack a transcription factor required for the generation of dendritic cells
      and the development of an organized thymic medulla. Rel B-deficient animals
      express very low levels of TCA4 in the thymus and little or no TCA4 in the
      periphery. At subnanomolar concentrations, TCA4 is a chemoattractant of mature T
      cells; the potential role of this novel chemokine in facilitating normal
      lymphocyte traffic is discussed. TCA4 is also a chemoattractant of cultured
      mesangial cells. Neutralizing anti-TCA4 mAb was used to demonstrate the
      specificity of TCA4-mediated cell migration. Finally, competitive binding studies
      with a SV40-transformed mouse mesangial cell line demonstrated that other murine
      beta-chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein
      1alpha, macrophage inflammatory protein-1beta, and thymus-derived chemotactic
      agent 3) do not compete for TCA4 binding.

PMID- 9548512
TI  - Protective antibodies develop, and murine Lyme arthritis regresses, in the
      absence of MHC class II and CD4+ T cells.
AB  - Murine Lyme borreliosis is characterized by arthritis and carditis that are most
      severe at 2 to 3 wk, then regress during the course of persistent infection.
      Borrelia burgdorferi-specific Abs and CD4+ T cells have been implicated in the
      resolution phase of arthritis. Therefore, MHC class II transactivator (CIITA)
      deficient mice that do not express conventional class II molecules and lack the
      normal CD4 repertoire were used to investigate the role of MHC class II-mediated
      responses in Lyme disease. The development of arthritis and carditis, and the
      resolution of arthritis, were similar in CIITA-deficient and control C57/BL6
      mice. In contrast, the resolution of carditis was delayed in CIITA-deficient
      animals compared with controls. Moreover, CIITA-deficient mice developed B.
      burgdorferi-specific IgG2b Abs, and sera from these animals passively protected
      naive C3H/HeN mice from challenge inoculation and cleared B. burgdorferi from 2
      day-infected C.B.17 SCID mice. These data suggest that CD4+ T cells and MHC class
      II-mediated responses are not required for the generation of protective Abs or
      the regression of arthritis, but may be important in the resolution of Lyme
      carditis in mice.

PMID- 9548513
TI  - Suppression of collagen-induced arthritis by continuous administration of IL-4.
AB  - The onset of collagen-induced arthritis in DBA/1 mice is accompanied by a
      predominantly Th1 response, characterized by production of the proinflammatory
      cytokines IFN-gamma and TNF-alpha, and a predominance of IgG2a anti-collagen Abs.
      This study has primarily addressed the effects of continuous administration of
      exogenous IL-4, a Th2 cytokine, on collagen-induced arthritis in terms of time of
      onset, clinical symptoms, and histologic changes compared with those in untreated
      controls. The contributions of Th1 and Th2 cell responses were studied by
      examining anti-CII IgG subclasses, serum IgE levels, and cytokine production by
      synovial membrane and lymph node cell cultures. Continuous exposure to IL-4 for
      28 days significantly delayed the onset of arthritis from 19 to 37 days and
      suppressed clinical symptoms. Arthritis occurred approximately 13 to 24 days
      after treatment ceased. Thereafter, the severity and duration of clinical
      symptoms were similar to those in control animals, although both joint damage and
      inflammation at the histologic and cellular levels were less severe than those in
      untreated controls. During IL-4 treatment, anti-collagen Ab levels were reduced
      (most significantly those of the IgG2a subclass), histology scores were lower,
      and the most striking effect was a 1000-fold decrease in TNF-alpha secretion by
      synovial cells. No significant differences in IgE levels were found between
      controls and IL-4-treated mice. These data suggest that the anti-inflammatory
      properties of IL-4 are mediated in part by down-regulation of Th1 responses
      rather than up-regulation of Th2 responses.

PMID- 9548514
TI  - Induction of high affinity fibroblast growth factor receptor expression and
      proliferation in human endothelial cells by anti-HLA antibodies: a possible
      mechanism for transplant atherosclerosis.
AB  - The major limitation to long term survival of organ allografts is chronic
      rejection, which is manifested as atherosclerosis of the vessels of the
      transplanted organ. There is a significant association between transplant
      atherosclerosis and the development of Abs to the disparate HLA Ags present on
      the graft vasculature. We have investigated the effect of anti-HLA Abs on
      endothelial cells (EC) and smooth muscle cells cultured in vitro. Ab ligation of
      class I molecules on ECs results in increased high affinity fibroblast growth
      factor receptor mRNA expression, and enhanced basic fibroblast growth factor
      ligand binding. Ab binding to class I molecules on EC and smooth muscle cells is
      also accompanied by augmented cell proliferation. These results suggest that the
      intimal thickening observed in transplant atherosclerosis is the result of the
      proliferative effects of anti-HLA Abs.

PMID- 9548515
TI  - Priming with IL-4 and IL-13 during HIV-1 infection restores in vitro IL-12
      production by mononuclear cells of HIV-infected patients.
AB  - The production of proinflammatory cytokines can be regulated by several factors
      that exert activating or inhibitory effects. IL-4, IL-10, IL-13, TGF-beta, and
      PGE2 have demonstrated a very wide range of potent macrophage-deactivating
      activities and, specifically, down-regulation of the production of many
      proinflammatory monokines. IL-12 plays a key role during immune response by
      providing a link between natural resistance and adaptive immunity. We and others
      have previously shown an impairment in IL-12 production by PBMC from HIV-1
      infected individuals in response to various stimuli, but defining the mechanism
      responsible remains elusive. In this study, we observed that pretreatment of PBMC
      from patients with IL-4 or IL-13 for 24 h primes the cells for enhanced
      production of IL-12 in response to Staphylococcus aureus, and almost completely
      restores their deficient IL-12 production when compared with healthy controls.
      Although this priming effect was completely abrogated by IL-10 and PGE2, IL-10
      was produced equivalently by untreated and IL-4- or IL-13-pretreated PBMC from
      both patients and controls. Additionally, indomethacin, which shuts off PGE2
      synthesis, and cAMP-blocking reagents failed to restore or enhance IL-12
      production. The priming effect of IL-4 and IL-13 is at the transcription level
      for both p40 and p35 genes. This complete restoration of IL-12 production by Th2
      associated cytokines was unexpected in light of the mutually antagonistic roles
      of IL-12 and IL-4 in promoting Th1 or Th2 immune responses.

PMID- 9548516
TI  - A single nonamer from the Yersinia 60-kDa heat shock protein is the target of HLA
      B27-restricted CTL response in Yersinia-induced reactive arthritis.
AB  - The reason for the high association of HLA-B27 with diseases such as ankylosing
      spondylitis and reactive arthritis is not clear. In reactive arthritis, the
      triggering bacteria are known, thus allowing investigation of their interaction
      with HLA-B27. CTL lines derived from five patients with Yersinia-induced reactive
      arthritis were raised by repeated stimulation in vitro with either Yersinia
      infected autologous macrophages (four patients) or pooled peptides (three
      patients) having the HLA-B27-binding motif. The peptides were derived from five
      Yersinia proteins and from the chlamydial 57-kDa heat shock protein (hsp).
      Cytotoxicity of T cell lines was then tested against these peptides. Lytic
      activity was obtained with T cells stimulated with viable Yersinia or pooled
      peptides. Targets successfully used for lysis were cells pulsed with peptides
      from the Yersinia 60-kDa hsp, but not cells pulsed with peptides from other
      Yersinia proteins or the chlamydial hsp. T cell lines raised with 60-kDa peptides
      also lysed targets infected with Yersinia. Most interestingly, all three CTL
      lines tested (one raised with Yersinia; two with pool of peptides) recognized
      only one single peptide (321-329) of seven tested from the Yersinia hsp60.
      Cytotoxicity occurred only when target cells were matched for HLA-B27. This
      identification of an immunogenic peptide derived from an arthritogenic bacterium
      and presented by HLA-B27 opens the way for future investigation of the role of T
      cells specific for this peptide or cross-reacting peptides, in the
      immunopathology of HLA-B27-associated diseases.

PMID- 9548517
TI  - IgE from latex-allergic patients binds to cloned and expressed B cell epitopes of
      prohevein.
AB  - Prohevein is one of the major allergens associated with latex allergy. In the
      present study, we identified IgE binding regions of prohevein, and expressed
      multiple IgE binding epitopes by selective cloning. These truncated polypeptides
      were then used to demonstrate IgE in the sera of patients. Decapeptides of
      prohevein were synthesized on derivatized cellulose membrane with an offset of
      one amino acid. The IgE reactivity of these linear peptides was evaluated
      separately using pooled sera from latex-allergic health care workers (HCW) and
      spina bifida (SB) patients. A total of 10 IgE binding epitopes representing
      unique as well as shared epitopes from both the N- and C-domains of the prohevein
      were identified. Recombinant polypeptides were constructed based on the
      identified epitopes, and clones carrying DNA fragments were overexpressed. These
      recombinant peptides were evaluated for IgE binding with sera from HCW, SB, and
      normal individuals. Recombinant prohevein, hevein, and the C-domain exhibited IgE
      binding in 84, 88, and 40% of HCW sera, respectively, as against reactivity of
      84% with crude latex allergens. However, only 48% of the sera from SB patients
      showed IgE binding with recombinant prohevein, while 56 and 28% had reactivity
      with recombinant N- and C-domains, respectively. Among the three remaining
      recombinant peptides of the C-domain, only CA44-103 showed IgE binding with SB
      patients. The results of the present study suggest that linear IgE epitope
      analysis and construction of recombinant peptides increase the sensitivity and
      specificity of the immunodiagnosis of latex allergy and provide more information
      on the immunopathogenesis of hypersensitivity reaction mediated by type I
      allergy.

PMID- 9548518
TI  - Cell death during autoimmune demyelination: effector but not target cells are
      eliminated by apoptosis.
AB  - The Fas and FasL apoptotic pathway was investigated by protein
      immunohistochemistry, flow cytometry, and reverse transcriptase-PCR analysis to
      assess whether it is involved in the elimination of target and/or effector cells
      from the central nervous system (CNS) during adoptively transferred chronic
      relapsing experimental autoimmune encephalomyelitis (EAE), a model for multiple
      sclerosis. In addition to Fas and FasL, we studied Bax, an intracellular protein
      of the apoptotic cascade, the Bax antagonist and anti-apoptotic molecule Bcl-2,
      and DNA fragmentation, the final step in the apoptotic pathway. Infiltrating CD4+
      T cells and parenchymal microglia expressed Fas, FasL, and Bax, and about half of
      these cells showed DNA fragmentation, a combination indicative of ongoing
      apoptosis. Using flow cytometry and reverse transcriptase-PCR, a positive
      correlation was seen between disease activity and up-regulation of the Fas
      system; in fact, Fas and FasL were expressed at low levels at the onset of EAE
      and increased at the height of disease to involve about one-third of all
      infiltrating lymphocytes. In the normal CNS, Fas immunoreactivity was
      constitutively present at low levels on oligodendrocytes and was up-regulated in
      the CNS during the course of EAE. However, oligodendrocytes showed no Bax
      reactivity or DNA fragmentation and expressed high levels of Bcl-2, as did the
      majority of infiltrating CD3+ cells, a pattern inconsistent with apoptosis. Thus,
      while molecules of the apoptotic cascade are well represented in the CNS during
      EAE, their expression correlates with elimination of infiltrating cells and
      microglia, not the myelinating cell, the oligodendrocyte.

PMID- 9548519
TI  - Ligation of cell surface CD4 inhibits activation-induced death of human T
      lymphocytes at the level of Fas ligand expression.
AB  - Cross-linking of cell surface CD4 molecules by anti-CD4 mAb or HIV-1 gp120/anti
      gp120 Ab primes resting T lymphocytes for activation-induced cell death (AICD)
      triggered via the CD3/TCR complex. In striking contrast, we demonstrate here that
      preincubation of activated human CD4+ T cells with anti-CD4 mAb consistently
      inhibited AICD triggered via anti-CD3 mAb or Staphylococcus aureus enterotoxin A
      superantigen. Inhibition of AICD of CD4+ T cell clones was also observed with
      F(ab')2, but not with Fab, of anti-CD4 mAb. Moreover, soluble HIV-1 gp120, but
      not rIL-16, inhibited AICD stimulated by S. aureus enterotoxin A. In susceptible
      clones, CD4 ligation prevented the up-regulation of Fas ligand mRNA and cell
      surface expression in response to anti-CD3 mAb or superantigen stimulation.
      CD3/TCR-dependent protein tyrosine phosphorylation and cytokine production were
      also prevented by preceding CD4 ligation. The inhibition of AICD due to the
      prevention of Fas ligand upregulation reveals a novel immunoregulatory
      consequence of CD4 ligation that might play a role in HIV infection and in the
      therapeutic application of anti-CD4 mAb.

PMID- 9548520
TI  - Notice of duplicate publication.

PMID- 9548521
TI  - Molecular biology of axonal outgrowth. 1. Growth cones and GAP-43.

PMID- 9548522
TI  - Optic chiasm astrocytomas of childhood. 1. Long-term follow-up.
AB  - We reviewed 61 patients seen from 1975 to 1994 with a biopsy-confirmed optic
      chiasm astrocytoma or a characteristic clinical and imaging presentation. The
      mean age at diagnosis was 72 months, including 30 who were less than 5 years old.
      The mean tumor diameter at presentation was 31 mm among 54 tumors measured.
      Tumors involved the optic nerve in 41, hypothalamus in 38, optic tract in 15, and
      optic radiations in 2. Four patients, all with neurofibromatosis, received no
      treatment. Forty patients received conventional radiation therapy at a mean age
      of 89 months. Chemotherapy was given to 19 children and 7 of these were followed
      for greater than 1 year. Six of these 7 had progressive disease which required
      subsequent surgery and/or radiation therapy. Thirty-six patients underwent
      surgery. We restricted our analysis of outcome to those 38 patients followed for
      longer than 60 months. Development was normal in 13%, mildly disabled in 53%,
      severely disabled in 21% and dead in 13%. Children were severely disabled or dead
      in 47% if younger than 5 years at diagnosis, and 21% if older. There was no
      endocrine dysfunction in 18% and new endocrine failure was seen in 61%. More
      posterior tumors did not portend a poorer prognosis. Children less than 5 years
      old had a poorer prognosis. Neurofibromatosis did not have a marked effect on
      outcome. Intracranial hypertension was an indicator of a poor prognosis. No
      specific treatment modality was clearly superior in terms of long-term survival
      or improvement in quality of life.

PMID- 9548523
TI  - Optic chiasm astrocytomas of childhood. 2. Surgical management.
AB  - We presented our experience from 1975 to 1994 with emphasis on the long term
      follow-up of children with optic chiasm astrocytomas in part I. In part II we
      describe the surgical management of 20 patients with the diagnosis of an
      astrocytoma of the optic chiasm confirmed by biopsy. These patients underwent
      surgery by the senior author between 1988 and 1994. The patients and the tumors
      in this series are comparable in age, sex, and presentation and imaging
      characteristics to other series. Surgery was undertaken with the intent to reduce
      tumor volume and mass effect and in certain cases to confirm the diagnosis. The
      patients' mean age at the time of surgery was 81 (range 18-216) months. The
      surgical approaches used were pterional in 11 patients, transorbital/subfrontal
      in 8, and subfrontal in 1 patient. Greater than 50% of the tumor was resected in
      8 patients, less than 50% was resected in 9, and biopsy only was achieved in 3
      patients. Larger tumors were more likely to have magnetic resonance imaging
      documented debulking of tumor. Permanent morbidity included mild visual loss,
      diabetes insipidus, mild hemiparesis, and panhypopituitarism in 1 patient each.
      There was no surgical mortality. The likelihood of resecting greater than 50% of
      the tumor was higher in those with a diameter greater than 25 mm. The indications
      for craniotomy are (1) to debulk symptomatic tumors greater than 50 mm in
      diameter which are exophytic or cystic; (2) to relieve obstruction at the foramen
      of Monro, and (3) for diagnostic biopsy.

PMID- 9548524
TI  - Surgical management of sagittal synostosis: a comparative analysis of strip
      craniectomy and calvarial vault remodeling.
AB  - Although surgical treatment of sagittal synostosis has become normative, the
      procedure of choice is still debated. This retrospective analysis, during a 10
      year period (1986-1995) at Children's Hospital Los Angeles, compares the more
      conservative strip craniectomy (SC) procedure with a more extensive occipital
      reduction-biparietal widening calvarial vault remodeling (CVR) technique for the
      management of sagittal synostosis. SC was performed in 72 patients (61%) and CVR
      in 46 (39%). Patients undergoing CVR were older (mean 5.3 vs. 3.0 months, p <
      0.01), the procedure time longer (mean 126 min vs. 72 min, p < 0.01),
      intraoperative blood loss greater (mean 243 vs. 54 cm3, p < 0.01), and the
      frequency of intraoperative blood transfusion increased (100 vs. 38%, p < 0.01;
      mean volume 357 vs. 51 cm3, p < 0.01) compared to patients undergoing SC. No
      significant intraoperative complications occurred in either group. The total time
      of hospitalization was similar (mean 4.4 vs. 3.8 days, p = 0.02). No
      neurological, hematological, or transfusion-related complications or deaths were
      encountered in either group. Cosmetic outcomes were significantly better in the
      CVR group with 79% rated as excellent compared to 41% in the SC group (p < 0.01).
      Fifty-nine percent of the SC patients manifested bony defects at last follow-up
      visit. Two SC patients required reoperation for poor cosmetic outcomes; CVR was
      successfully employed in both cases. These findings demonstrate that CVR is
      superior to SC in providing immediate and lasting correction of calvarial
      deformities secondary to sagittal synostosis. The optimal age at time of surgery
      is <6 months; however, CVR can be utilized throughout infancy, while SC becomes
      progressively less effective after 6 months of age. No significant complications
      were observed in either group, despite the increased operative manipulation and
      greater incidence of blood transfusion in the CVR patients.

PMID- 9548525
TI  - Treatment of hydrocephalus with third ventriculocisternostomy: outcome and CSF
      flow patterns.
AB  - Third ventriculocisternostomy was performed in 23 patients for management of
      hydrocephalus. The procedure was offered as the first treatment in 18 cases and
      in lieu of a shunt revision in 4 cases. Median follow-up was 17 months (range 7
      44 months). In 16 patients the operation was successful in treating their
      symptoms (73%). Cine MRI was helpful in evaluating patients with persistent
      ventriculomegaly. Resolution of symptoms in association with decreased
      ventricular size correlated best with outcome following this procedure. Third
      ventriculocisternostomy is technically safe and minimally invasive and should be
      offered as the first procedure in the management of noncommunicating
      hydrocephalus.

PMID- 9548526
TI  - Diffuse infiltrating astrocytoma of the cervicomedullary region:
      clinicopathologic entity.
AB  - Recent imaging and neurosurgical techniques have led to an improvement in the
      surgical management of children with brainstem tumors (BSTs). Many children with
      tumors previously considered 'inoperable' can now benefit from surgery. Increased
      experience has brought about new theories concerning the growth pattern, natural
      history, classification and optimal management of these tumors. Cervicomedullary
      (CM) tumors commonly have an indolent presentation reflecting either medullary or
      cervical spinal cord dysfunction and tend to arise in the upper cervical cord
      growing into the medulla in a posterior exophytic fashion. Intrinsic BSTs often
      present acutely with cranial nerve dysfunction and generally arise in the pons
      with a diffuse infiltrating growth pattern. A 21-month-old patient had developed
      feeding difficulty and reactive airway disease at approximately 8 months of age.
      MRI showed a diffuse, nonenhancing tumor in the CM region. Following radical
      resection, and an unremarkable perioperative course, he aspirated, developed
      pulmonary insufficiency and expired. Postmortem examination revealed a low-grade
      diffuse fibrillary astrocytoma extending from C6 to the medulla. The medullary
      portion arose in a paramedian location and infiltrated dorsally into the fourth
      ventricle, the obex, the leptomeninges, and the adjacent cerebellum. This case
      demonstrates the growth pattern of a distinct subset of CM tumors that behave in
      a manner similar to intrinsic diffuse BST. Future identification of these subsets
      by a careful analysis of the clinical presentation and MRI images will enable
      better operative planning and optimal management.

PMID- 9548527
TI  - Two-year-old boy with seizures.

PMID- 9548528
TI  - Preparation and photoactivation of caged fluorophores and caged proteins using a
      new class of heterobifunctional, photocleavable cross-linking reagents.
AB  - The design, synthesis, and spectroscopic and chemical properties of four members
      of a new class of heterobifunctional photocleavable (caged) cross-linking
      reagents were described. One of the two reactive groups of the cross-linker
      reacted with amino groups to form the corresponding photolabile carbamates. Amino
      group containing compounds or proteins caged with these reagents can be coupled
      through the thiol reactive oxirane group of the cross-linker to a different
      biomolecule or to a thiol-derivatized surface. The 3,4-dimethoxy-6-nitrophenyl
      photoisomerization group of the reagent was physically and chemically isolated
      from the cross-linking functionality, and the high extinction coefficient and red
      shifted action spectrum of this chromophore make it suitable for photoactivation
      applications of caged compounds on surfaces or in living cells. The bifunctional,
      photocleavable cross-linking reagents were used to prepare a thiol reactive caged
      rhodamine 110. The new reagents and conjugation procedures described may be used
      as part of a general procedure to cage the activity of proteins by physically
      masking binding sites.

PMID- 9548529
TI  - Cell targeting by glycosidic telomers. Specific recognition of the Kb CWL1 lectin
      by galactosylated telomers.
AB  - This work deals with the synthesis and lectinic recognition ability of
      galactosylated telomers. To investigate if telomeric carriers could exhibit
      cellular recognition properties, we have synthesized mono- and polygalactosylated
      tris(hydroxymethyl)acrylamidomethane (THAM) telomers. The affinity of such
      macromolecular drug carriers toward a receptor, the yeast Kb CWL1 lectin, was
      defined, and the influence of mono- or polygalactosylation of THAM units on the
      recognition phenomenon was assessed. The lectinic affinity of the compounds was
      estimated by measuring the inhibition of yeast aggregation. The average degree of
      polymerization as well as the hydrophilic-lipophilic balance of such
      galactosylated telomers affects their recognition ability for the lectin.

PMID- 9548530
TI  - A homobifunctional rhodamine for labeling proteins with defined orientations of a
      fluorophore.
AB  - The synthesis and characterization of a bifunctional rhodamine dye bearing 2
      (iodoacetamido)ethyl substituents on the 3'- and 6'-nitrogen atoms is described.
      Aspects of the conversion of chloroacetamides to iodoacetamides are discussed,
      including a remarkably mild dehalogenation of an aromatic haloacetamide in the
      presence of NaI and camphorsulfonic acid. The bifunctional rhodamine has been
      designed for two-site, 1:1 labeling of proteins that contain two suitably
      disposed cysteine residues and is intended to constrain the orientation of the
      rhodamine absorption and emission dipoles in a predictable relationship to the
      protein structure.

PMID- 9548531
TI  - Hybridization characteristics of biomolecular adaptors, covalent DNA-
      streptavidin conjugates.
AB  - Semisynthetic, covalent streptavidin-DNA adducts are versatile molecular
      connectors for the fabrication of both nano- and microstructured protein arrays
      by use of DNA hybridization. In this study, the hybridization characteristics of
      six adduct species, each containing a different DNA sequence of 21 or 24 bases,
      have been compared. First, the adducts were conjugated to biotinylated alkaline
      phosphatase, and their binding to immobilized oligomer complements of similar
      lengths was quantified in a microplate assay. The binding efficiency observed
      varied to a great extent with the specific sequence of the oligonucleotide
      attached, and could not be predicted from affiliated thermodynamic data of duplex
      stability. To further elucidate the hybridization properties, the hybridization
      rate constants of association and dissociation (kassn and kdissn) have been
      determined for both unconjugated oligonucleotides and protein adducts, using a
      surface plasmon resonance biosensor. The kassn values observed for the
      oligonucleotides are in the range of 9 x 10(3) to 2 x 10(5) M[-1] s(-1) and
      correlate with structural properties of the probe strands. Up to 3-fold decreased
      kassn values were obtained for the corresponding protein adducts. Likewise,
      values were observed for kdissn ranging from 1.4 x 10(-4) to 1.9 x 10(-5) s[-1]
      for the oligonucleotides. The dissociation of the analogous protein conjugates
      was reduced by up to 5-fold. The extent of this decrease correlates with the
      formation of homodimeric or intramolecular aggregation of probe strands. A
      mechanistic model for explaining these data is based on attractive intramolecular
      interaction between the nucleic acid and protein moiety.

PMID- 9548532
TI  - Extending insulin action in vivo by conjugation to carboxymethyl dextran.
AB  - The biochemical and pharmacological properties of bioactive peptides and proteins
      can be altered by conjugation with polymers. This report describes site-specific
      attachment of insulin to activated carboxyl groups of carboxymethyl dextran (CMD,
      MW=51000) through the GlyA1 insulin amino group. On average, three or four
      insulin molecules were grafted to a CMD linear chain. Coupled insulin molecules
      were properly folded, and the bioactivity of conjugated insulin in the blood
      glucose depression assay was 9.6 IU/mg, which was only 2.6 times less than that
      for native insulin. The cell growth study indicated that the CMD-insulin
      conjugate was as mitogenic as insulin on vascular smooth muscle cells, whereas
      the starting CMD polymer was not. The insulin receptor binding constant of the
      conjugate (3.6 x 10[9] M[-1]) compared well with that of native insulin (7.6 x
      10[9] M[-1]), indicating that the CMD chain does not present any major
      constraints to binding. Plasma clearance of CMD-insulin obeyed a two-compartment
      pharmacokinetic (PK) model with a CMD-insulin conjugate plasma elimination half
      life of 114.1 min, which was significantly longer than that of soluble Zn-insulin
      (12.4 min). In contrast, pharmacodynamic (PD) profiles (blood glucose lowering
      effects) after intravenous (iv) administration of the conjugate or insulin in
      rats were not different. Subcutaneous (sc) administration of the conjugate
      resulted in a significantly prolonged plasma profile with a noncompartmental PK
      parameter mean residence time (MRT) of 103.5 min which was significantly longer
      than that of soluble Zn-insulin (40.5 min). This was reflected in the protracted
      PD effect of sc administered conjugate with time needed to reach minimum glucose
      concentration Tnadir of 95.7 min, which was significantly longer than that of
      insulin (62 min). We conclude that the conjugation of insulin to CMD leads to a
      bioactive conjugate with a delayed sc PD profile showing prolonged response,
      resembling intermediate acting insulin preparations.

PMID- 9548533
TI  - Antibody-mediated versus nontargeted delivery in a human small cell lung
      carcinoma model.
AB  - The uptake of macromolecular agents in tumor cells (LX-1, human small cell lung
      carcinoma) and in corresponding tumor xenografts was compared in a parallel study
      utilizing a long-circulating biocompatible graft copolymer, MPEGs-PL-DTPA
      [Bogdanov, A., Jr., et al. (1995) Adv. Drug Delivery Rev. 16, 335-348; Bogdanov,
      A., Jr., et al. (1996) Bioconjugate Chem. 7, 144-149] and a tumor-specific
      chimeric monoclonal antibody, BR96 [Hellstrom, I., et al. (1990) Cancer Res. 50,
      2183-2190; Garrigues, J., et al. (1993) Am. J. Pathol. 142, 607-622]. Covalent
      grafted conjugates of methoxy-(polyethylene glycol)succinate and polylysine and
      BR96 were modified with DTPA, biotinyl, or rhodamine-X-residues. Using
      radionuclide and fluorescent labeled derivatives of the copolymer and the
      antibody, we established that (1) the copolymer does not associate with the
      plasma membrane in N-ethylmaleimide-treated cells and is slowly internalized by
      live cells at 37 degrees C; (2) the antibody binds rapidly to the surface of LX-1
      cells and shows active internalization in vesicles with a subsequent slow
      decrease in the cell-associated antibody concentration; (3) LX-1 cells bear more
      than 1 million BR96 binding sites/cell (with an apparent Kd of 4.5 x 10[-7] M);
      and (4) intravesicular fluorescence intensity in LX-1 cells was linearly
      dependent on copolymer concentration, suggesting fluid phase endocytosis. Tumor
      localization by nuclear imaging, biodistribution, microdistribution by histology,
      and determination of tumor cell fraction uptake was performed in LX-1 tumor
      xenografts. In vivo study showed that MPEGs-PL-DTPA progressively accumulates in
      the tumor, yielding from 2.8+/-1.5% injected dose per gram of tissue (ID/g) at 24
      h to 5.2+/-1.7% ID/g of tissue at 48 h. The antibody accumulation peaked at 24 h
      (6.0+/-3.2% ID/g) and decreased thereafter. We determined that at 24 h 43.9+/
      11.29% of the polymer accumulated in the tumor was associated with tumor cell
      fraction with the remainder of the accumulated dose localized in the
      interstitium. Accumulation of the biotinylated graft copolymer and the antibody
      in LX-1 xenografts and their uptake in cells were confirmed by histology using
      avidin-peroxidase staining. Our study demonstrates that, although BR96 is highly
      specific in vitro, tumoral drug delivery in vivo can be equally high with long
      circulating graft copolymers because of slow extravasation at the tumor site.

PMID- 9548534
TI  - Identification of the soluble in vivo metabolites of indium-111
      diethylenetriaminepentaacetic acid-D-Phe1-octreotide.
AB  - Indium-111-diethylenetriaminepentaacetic Acid-D-phenylalanine-octreotide ([111]In
      DTPA-octreotide) is a cyclic eight amino acid somatostatin analogue which is
      approved for gamma scintigraphy of neuroendocrine tumors. To address the factors
      that contribute to liver and kidney retention of this radiopharmaceutical, its
      metabolism was evaluated in normal and tumor-bearing rats. The soluble fractions
      from nontarget (liver and kidney) and target (tumor, pancreas, adrenals) organ
      homogenates were analyzed out to 21 h postinjection, and urine was analyzed out
      to 12 h postinjection. The blood was analyzed at shorter time intervals due to
      the rapid clearance of (111)In-DTPA-octreotide. Radio-TLC and HPLC were used to
      analyze organ homogenates, blood, and urine. By TLC, intact (111)In-DTPA
      octreotide was resolved from the soluble metabolites, and a similar apparent rate
      of metabolism was observed in the liver, kidney, tumor, and pancreas with
      approximately 30% intact (111)In-DTPA-octreotide at 4 h postinjection. In the
      adrenals, metabolism occurred more slowly with approximately 60% intact (111)In
      DTPAoctreotide at 4 h postinjection. At 4 h postinjection, the activity excreted
      in the urine consisted of 85% intact (111)In-DTPA-octreotide. HPLC provided
      resolution of the individual extractable metabolites. In an attempt to identify
      these metabolites, two DTPA-amino acid sequences were synthesized: DTPA-D-Phe-Cys
      and DTPA-D-Phe. Under the conditions used for metabolite analysis, (111)In-DTPA-D
      Phe-Cys-OH eluted at 14.6 min and (111)In-DTPA-D-Phe-OH eluted at 7.0 min. Each
      of these standard sequences was combined with the soluble portion of the organ
      homogenate and was shown by HPLC to coelute with the metabolites. These data
      suggest that (111)In-DTPA-octreotide was initially degraded to (111)In-DTPA-D-Phe
      Cys-OH and (111)In-DTPA-D-Phe-OH. The (111)In-DTPA-D-Phe-Cys-OH was further
      degraded to (111)In-DTPA-D-Phe-OH, which appeared to be the final metabolite that
      was extracted from the organs. From these results, it can be concluded that at
      longer time points (> 2 h postinjection) a significant amount of (111)In was
      retained in nontarget organs as (111)In-DTPA-D-Phe-OH and (111)In-DTPA-D-Phe-Cys
      OH and not as intact (111)In-DTPA-octreotide.

PMID- 9548535
TI  - Interleukin 7 (IL-7) receptor-specific cell killing by DAB389 IL-7: a novel agent
      for the elimination of IL-7 receptor positive cells.
AB  - Interleukin 7 (IL-7) induces the proliferation of B cell progenitors in long-term
      bone marrow cultures, promotes the growth of resting fetal and adult thymocytes,
      and costimulates mature human T cell proliferation. IL-7 also induces cell growth
      in hematologic malignancies such as acute lymphoblastic leukemia, chronic
      lymphocytic leukemia, acute myelogenous leukemia, and Sezary syndrome. We have
      constructed a recombinant fusion protein, DAB389 IL-7, composed of the catalytic
      and transmembrane domains of diphtheria toxin (DT), fused to IL-7. We demonstrate
      that DAB389 IL-7 is selectively cytotoxic for only those cells bearing the IL-7
      receptor and that entry into target cells is mediated through the receptor. The
      nontoxic mutant, DA(E149S)B389 IL-7, was constructed and used to demonstrate that
      the catalytic domain of DT is responsible for the ADP ribosylation of elongation
      factor 2 that results in cytotoxicity. Finally, we demonstrate that DA(E149S)B389
      IL-7 induces the growth of IL-7-dependent cells, verifying the bioactivity of the
      IL-7 binding domain of DAB389 IL-7. We propose that DAB389 IL-7 may be an
      important reagent in studying the IL-7--IL-7 receptor complex and may possess
      potential as a therapeutic agent against IL-7 receptor-bearing hematologic
      malignancies.

PMID- 9548536
TI  - High-affinity no-carrier-added 99mTc-labeled chemotactic peptides for studies of
      inflammation in vivo.
AB  - Nalpha-for-Nle-Leu-Phe-Nle-Tyr-Lys, a chemotactic peptide that binds with high
      affinity to the chemoattractant receptor on granulocytes and monocytes, was
      labeled with 99mTc using the diaminedithiol (DADT) chelating system to coordinate
      the Tc. 99mTc labeling of the DADT-coupled peptide was accomplished in 84%
      overall yield (room temperature for 10 min) using [99mTc]glucoheptonate as the
      donor of prereduced Tc. HPLC analysis showed two major 99mTc-labeled peptide
      peaks, 99mTc-DADT-Pep-I and 99mTc-DADT-Pep-II, were obtained in a ratio of
      1:0.85. Using an iodoacetamide-derivatized gel to remove unlabeled peptide from
      the 99mTc labeling mixtures, essentially no-carrier-added (nca) high-specific
      activity 99mTc-labeled chemotactic peptides were obtained. The 99Tc analogues of
      the peptides were synthesized (72% yield) in a similar fashion and correlated
      with 99mTc complexes I and II by HPLC. In vitro competitive receptor binding
      assays of the isolated 99Tc analogues were performed against the tritiated
      chemotactic peptide [3H]N-for-Met-Leu-Phe ([3H]fMLF) using isolated granulocytes.
      The 99Tc-derivatized peptides showed similar binding affinities to the
      chemoattractant receptor as the unlabeled Nalpha-for-Nle-Leu-Phe-Nle-Tyr-Lys. The
      nca 99mTc-labeled peptides gave high contrast images of experimental inflammation
      in rabbits without causing neutropenia. Thus, it is feasible to attach the Tc
      DADT chelate to low-molecular weight receptor binding chemotactic peptides and
      retain substantial binding to the receptor. Chemotactic peptides labeled with
      99mTc via the DADT ligand system have the potential for imaging focal sites of
      inflammation without toxic effects, an important consideration in the successful
      utilization of chemotactic peptide agonists.

PMID- 9548537
TI  - Design, synthesis, and initial evaluation of high-affinity technetium bombesin
      analogues.
AB  - Potent antagonists of bombesin-like peptides have shown great potential for
      applications in cancer therapy. A 99mTc-labeled agent capable of identifying
      patients who could benefit from these emerging therapies would have a great
      impact on patient management. This study involves the synthesis and initial
      evaluation of technetium diaminedithiolate analogues derived from the potent
      bombesin analogue Pyr-Gln-Lys-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2
      (Lys3-bombesin). We coupled two diaminedithiol (DADT) bifunctional chelating
      agents (BCAs 1 and 2) to the Lys3 residue at the N-terminal region that is not
      required for binding to the receptor. 99mTc labeling was performed by ligand
      exchange on addition of [99mTc]glucoheptonate to a solution of the adduct at room
      temperature. Two products were obtained from each adduct on analysis by HPLC. The
      major to minor product ratios of the 99mTc-labeled analogues were 3:1 for
      products from BCA 1 and 9:1 for the products from BCA 2. Macroscopic amounts of
      the 99Tc analogues were similarly prepared using [99Tc]glucoheptonate. In this
      case, the major to minor ratios were 2:1 for the products from both BCAs. For
      initial evaluation of the binding of the Tc-labeled peptides to bombesin
      receptors, the 99Tc analogues were used in vitro in competitive binding assays in
      rat brain cortex membranes against [125I-Tyr4]bombesin. Results of the in vitro
      assays showed that the inhibition constants (Ki) of the major and minor products
      were 3.5+/-0.7 and 3.9+/-1.5 nM, respectively, for the products from BCA 1; and
      7.4+/-2.0 and 5.2+/-1.5 nM for the products derived from BCA 2, respectively. The
      high affinity exhibited by these technetium analogues is an indication of their
      potential for use in non-invasive in vivo biochemical characterization of cancers
      that possess receptors for bombesin.

PMID- 9548538
TI  - Structure characterization of functional histidine residues and carbethoxylated
      derivatives in peptides and proteins by mass spectrometry.
AB  - We developed a mass spectrometric method to precisely characterize the structures
      of the diethyl pyrocarbonate (DEP)-modified amino acid derivatives in intact
      peptides and proteins. Using acetate-buffered solutions for modification
      reactions improved the yields of DEP modification. UV quantification of
      carbethoxylation of angiotensin II was consistent with the degree of mass
      spectrometrically determined modification. Unequivocal identification of the
      modification sites in carbethoxylated angiotensin II derivatives was achieved by
      HPLC separation and mass spectrometric sequencing. With increasing concentrations
      of DEP, a gradual increase of carbethoxy groups, comprising biscarbethoxylation
      products, was detected in angiotensin II and in insulin. When using a high molar
      excess of DEP, histidine carbethoxylation was found together with modifications
      at alpha-amino groups and tyrosine residues. The sites of carbethoxylation in
      insulin were identified by MALDI-MS-peptide mapping analyses of the tryptic
      digestion mixtures from the nonreduced insulin derivatives and after reduction of
      disulfide bonds, demonstrating that histidine carbethoxylation was sufficiently
      stable during disulfide bond reduction and tryptic digestion at pH 7.5. The mass
      spectrometric identification of mono- and biscarbethoxylated histidine residues
      in insulin is in agreement with surface accessibilities of imidazolyl nitrogen
      atoms and seems to reflect the microenvironment of the protein tertiary
      structure. Thus, mass spectrometric peptide mapping analyses of carbethoxylated
      protein derivatives allowed both the simultaneous identification of histidine
      carbethoxylation in the presence of other modified groups and the detection of
      different chemical behavior of histidine residues by the unambiguous
      identification of mono- and bismodifications.

PMID- 9548539
TI  - Molecular characterization of a conformational epitope of hen egg white lysozyme
      by differential chemical modification of immune complexes and mass spectrometric
      peptide mapping.
AB  - A new approach for the characterization of conformationally dependent epitope
      structures in protein antigens is described using differential chemical
      modification of immune complexes in combination with mass spectrometric peptide
      mapping analysis. Well-established methods for epitope characterization are
      frequently not applicable to conformationally dependent epitopes, and direct
      methods of structure analysis such as X-ray crystallography of immune complexes
      have been successful only in a few cases. Our approach combines tertiary
      structure-selective chemical modification of immune complexes with the molecular
      characterization of reaction products by mass spectrometric peptide mapping. The
      comparison of the modification pattern of free and antibody-bound antigen
      provides the identification of residues protected from modification by the
      antibody. These residues hence are characterized as part of the epitope
      structure. The well-characterized hen egg white lysozyme and a corresponding
      monoclonal IgM-type antibody were investigated as a model system. Specific
      modification reactions for arginine, lysine, and tyrosine residues were
      performed, and the modification sites in free and antibody-bound antigen were
      determined by mass spectrometric peptide mapping. The R14 residue and residues
      K13 and K96 in the antibody-bound lysozyme were found to be protected from
      modification, comprising a surface of spatially adjacent residues by folding of
      the native protein. In contrast, other K and R residues as well as Y20 and Y23
      showed no significant shielding from modification in the immune complex. These
      results provided an estimation of the molecular epitope surface area of native
      lysozyme.

PMID- 9548540
TI  - Fluorescently detectable magnetic resonance imaging agents.
AB  - This report describes the synthesis, characterization, and in vivo testing of
      several bifunctional contrast-enhancing agents for optical and magnetic resonance
      imaging (MRI) of experimental animals. These new agents integrate the advantages
      of both techniques since they can be visualized simultaneously by light and MRI
      microscopy. Employing this strategy allows the same biological structures of a
      specimen to be studied at dramatically different resolutions and depths. The
      complexes possess a metal chelator for binding a paramagnetic ion, gadolinium
      (Gd3+), and a covalently attached fluorescent dye. The first class of complexes
      are low-molecular weight species that are composed of the macrocyclic tetraamine
      1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) as the metal
      chelating ligand coupled to tetramethylrhodamine. The second class of MRI
      enhancing agents are composed of high-molecular weight polymers that are membrane
      impermeable and once injected into a cell or cells are trapped inside. These
      complexes possess multiple copies of both the metal-chelator
      diethylenetriaminepentaacetic acid (DTPA) and the tetramethylrhodamine attached
      to a macromolecular framework of either poly(D-lysine) (pdl) or dextran. Images
      acquired of single cells after injection with these bifunctional agents enabled
      us to follow the relative motions and reorganizations of different cell layers
      during amphibian gastrulation and neurulation in Xenopus laevis embryos.

PMID- 9548541
TI  - Synthesis of disulfide-containing phospholipid analogs for the preparation of
      head group-specific lipid antigens: generation of phosphatidylserine antibodies.
AB  - In this report, we describe a new approach for the production of lipid antigens
      that elicit specific immune responses against phosphatidylserine (PS). Because
      phospholipids are small nonimmunogenic haptens, PS analogs containing activated
      coupling groups were synthesized and covalently attached to carrier proteins.
      Sulfhydryl-reactive PS was generated by acylation of 1-oleoyl-2-(aminocaproyl)
      phosphatidylcholine with N-succinimidyl-3-(2-pyridyldithio) propionate, converted
      to PS by phospholipase D-catalyzed base exchange with L-serine, and conjugated to
      carrier proteins by thiol-disulfide exchange. Antisera to these lipid hapten
      protein carrier conjugates were developed in rabbits. Antibodies bound PS but not
      phosphatidylcholine (PC), phosphatidylglycerol, phosphatidic acid, or
      phosphatidylethanolamine (PE) when presented together with PC. Inhibition studies
      using water-soluble lipid analogs and sonicated vesicles indicated that antibody
      specificity was directed toward the lipid's polar head group. These antibodies
      also inhibited the PS-dependent prothrombinase activity assay by approximately
      60%. These data show that the covalent coupling of phospholipid haptens to
      protein carriers via the lipid's fatty acyl side chains preserves its primary
      head group moiety for the production of specific lipid antibodies.

PMID- 9548542
TI  - Development and activities of a new melphalan prodrug designed for tumor
      selective activation.
AB  - The synthesis of C-Mel, a cephalosporin carbamate derivative of the clinically
      used alkylating agent melphalan, is described. C-Mel was designed as an
      anticancer nitrogen mustard prodrug that releases melphalan upon tumor-specific
      activation by targeted beta-lactamase (bL). The Km and kcat values for bL
      hydrolysis of C-Mel were 218 microM and 980 s(-1), respectively. In vitro
      cytotoxicity assays with 3677 human melanoma cells demonstrated that C-Mel was 40
      fold less toxic than melphalan and was activated in an immunologically specific
      manner by L49-sFv-bL, a recombinant fusion protein that binds to the
      melanotransferrin antigen on melanomas and on some carcinomas. L49-sFv-bL in
      combination with C-Mel led to regressions and cures of established subcutaneous
      3677 tumors in nude mice. The effects were significantly greater than those of
      melphalan, which did not result in any long-term regressions in this tumor model.
      The therapeutic effects were comparable to those obtained in mice treated with
      the previously described L49-sFv-bL/7-(4-carboxybutanamido)-cephalosporin mustard
      (CCM) combination. However, C-Mel may be more attractive than CCM for clinical
      development since the released drug is clinically approved.

PMID- 9548543
TI  - Membrane permeabilization and efficient gene transfer by a peptide containing
      several histidines.
AB  - We designed a peptide, H5WYG (GLFHAIAHFIHGGWHGLIHGWYG), that permeabilizes cell
      membrane at a slightly acidic pH but not at neutral pH. Absorbance, fluorescence,
      and circular dichroism spectra showed that H5WYG undergoes a dramatic
      conformational change between pH 7.0 and 6.0 that correlates with the protonation
      of the histidyl residues. Cell permeabilization studies monitored by flow
      cytometry on living cells showed that H5WYG permeabilizes the cell membrane with
      a great efficiency at pH 6.4 but was not active at neutral pH; at pH 6.8, the
      peptide permeabilized 50% of the cells at 20 degrees C within 10 min. H5WYG
      increased the expression of genes transferred to cells as glycosylated polylysine
      DNA complexes, and the transfection efficiency was not impaired in the presence
      of serum. Therefore, this peptide containing several histidines that become
      positively charged when the pH decreased to less than 7.0 is a suitable helper
      for delivering molecules into the cytosol upon either permeabilization of the
      plasma membrane induced by lowering the extracellular medium to pH 6.4 or
      permeabilization of the endosomal membrane induced by acidification of endosomes.

PMID- 9548544
TI  - Novel glycosynthons for glycoconjugate preparation:
      oligosaccharylpyroglutamylanilide derivatives.
AB  - The reducing sugar of an oligosaccharide reacting with the alpha-amino group of
      an amino acid is converted to an N-oligosaccharylamino acid which can then be
      stabilized by N-acylation. Oligosaccharides in solution in N,N-dimethylformamide
      reacted with alpha-glutamyl-p-nitroanilide at 50 degrees C for a few hours,
      leading to an N-oligosaccharylglutamyl-p-nitroanilide. Then, the gamma-carboxylic
      group of the glutamyl moiety, activated by adding (benzotriazol-1
      yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), reacted with the
      substituted alpha-amino group of the glutamyl residue, leading to an N
      oligosaccharylpyroglutamyl-p-nitroanilide within 0.5 h. Such a one-pot two-step
      reaction was shown to be very efficient in the case of a disaccharide such as
      lactose, or pentasaccharides such as lacto-N-fucopentaoses, Lewis(a) or Lewis(x).
      The glycosynthons were characterized by chromatography (HPAEC and HPLC); their
      molecular mass was determined by electrospray ionization mass spectrometry, and
      the glycosylamides were shown to have a beta-anomeric configuration on the basis
      of their proton NMR. The N-oligosaccharylpyroglutamyl-p-nitroanilides are quite
      stable at room temperature over a large pH range. They are easily converted to N
      oligosaccharylpyroglutamyl-p-isothiocyanatoanilides which can be used to prepare
      glycoconjugates such as cationic glycosylated polylysines suitable for
      specifically delivering genes or oligonucleotides in a sugar-dependent manner.

PMID- 9548545
TI  - Micropatterned immobilization of epidermal growth factor to regulate cell
      function.
AB  - Photoreactive epidermal growth factor (EGF) was synthesized by conjugating mouse
      EGF with photoreactive polyallylamine, which was synthesized by the coupling
      reaction of polyallylamine with N-[4-(azidobenzoyl)oxy]succinimide. The EGF
      derivative was pattern-immobilized onto a polystyrene plate by UV irradiation in
      the presence of a photomask in a prescribed micropattern. The patterned
      immobilization of EGF on the polystyrene plate was confirmed by immunostaining
      with anti-EGF antibody. Chinese hamster ovary (CHO) cells overexpressing EGF
      receptors were cultured on the micropatterned plate. The phosphorylated tyrosine
      residues of signal proteins, including EGF receptors, were detected only in the
      cells adhered in the EGF-immobilized area, and cell growth was observed only in
      the EGF-immobilized area. The cells growing in the EGF-immobilized area were
      partially stained by anti-phosphotyrosine antibody, when the area of EGF
      immobilization was smaller than the cell. The partial staining of activated
      proteins indicates that immobilization of EGF inhibited the free lateral
      diffusion and internalization of the activated EGF-EGF receptor complex. The
      enhanced cell growth is due to juxtacrine stimulation realized by immobilized
      EGF.

PMID- 9548546
TI  - A mild and efficient solid-support synthesis of novel oligonucleotide conjugates.
AB  - Conjugates of oligodeoxyribonucleotide phosphorothioate (ODN-PS) with folic acid,
      retinoic acid, arachidonic acid, and methoxypoly(ethylene glycol)propionic acid
      have been synthesized. The procedure involved the initial solid-phase preparation
      of 5'-amino-functionalized ODN-PS using N-pent-4-enoyl-derived (PNT) nucleoside
      phosphoramidites followed by conjugation of the oligonucleotide either to the
      ligand acids, using 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide as a coupling
      reagent, or to their corresponding succinimidyl derivatives. Subsequent exposure
      of the support to aqueous ammonium hydroxide (28%, 2 h, 55 degrees C) resulted in
      the release of the fully deprotected ODN conjugates, which were purified by
      reversed-phase HPLC or by preparative polyacrylamide gel electrophoresis. The
      identity of the oligonucleotide conjugates was confirmed by MALDI-TOF mass
      spectral analysis.

PMID- 9548547
TI  - Characterization of interpolyelectrolyte complexes between double-stranded DNA
      and polylysine comb-type copolymers having hydrophilic side chains.
AB  - The polyionic interaction between DNA and polycations grafted with hydrophilic
      dextran side chains was evaluated. The comb-type copolymers, poly(L-lysine)-graft
      dextran, were successfully prepared by employing a reductive amination reaction
      between epsilon-amino groups of poly(L-lysine) (PLL) and the reductive ends of
      dextran (Dex). A coupling efficacy on the order of 70% was obtained regardless of
      intrinsic philicities of the solvents used, either aqueous buffer or DMSO. The
      resulting graft copolymers, which varied in the degree of grafting and the length
      of hydrophilic side chains, formed a soluble complex with DNA. They also affected
      the melting behavior of double-stranded DNA (dsDNA) in different ways. Copolymers
      having a high degree of grafting thermally stabilized dsDNA without affecting its
      reversible transition between single-stranded and double-stranded forms. However,
      copolymers with a low degree of grafting or with a high degree of grafting of
      short dextran chains impeded the reversibility of this transition. Furthermore,
      highly grafted copolymers also accelerated the hybridization of DNA strands in a
      low-ionic strength medium. It is of particular note that these copolymers
      scarcely altered circular dichroismic signals of dsDNA even when the copolymers
      were added in excess. This suggested that the copolymer interacted with dsDNA
      without affecting its native structure or physicochemical properties. Finally,
      the copolymer even formed a stable complex with a short oligonucleotide (20
      bases). We, therefore, concluded that, by regulating the degree of grafting and
      the molecular weight of grafted side chains, it would be possible to design novel
      different graft copolymers capable of acting as carriers of functional genes to
      target cells or tissue.

PMID- 9548548
TI  - Synthesis of heterobifunctional poly(ethylene glycol) with a reducing
      monosaccharide residue at one end.
AB  - A new synthetic method for a heterobifunctional poly(ethylene glycol) (PEG)
      having a monosaccharide moiety at one end was created. PEG with a reducing
      monosaccharide residue at the alpha-end, which is linked to a defined position of
      the sugar molecule, could be prepared via the anionic polymerization of ethylene
      oxide (EO) initiated with a potassium alkolate of a protected monosaccharide such
      as 1,2;5,6-di-O-isopropylidene-D-glucofuranose (DIGL), 1,2;3,4-di-O
      isopropylidene-D-galactopyranose (DIGA), and 1,2-O-isopropylidene-3,5-O
      benzylidene-D-glucofuranose (IBGL). The resulting PEGs possess the corresponding
      sugar molecule at the alpha-chain end and a hydroxyl group at the omega-chain
      end. The omega-chain end could be converted to several functional groups such as
      allyl, amino, and hydroxycarbonyl groups in high yield. Such heterobifunctional
      PEGs possessing a reducing monosaccharide residue at the alpha-end are one of the
      promising tools for bioconjugate chemistries.

PMID- 9548550
TI  - Subicular efferents are organized mostly as parallel projections: a double
      labeling, retrograde-tracing study in the rat.
AB  - To understand the functional relevance of the subiculum as a major distributor of
      hippocampally processed information, detailed information about its neuronal
      organization is necessary. A striking feature of the subiculum is that it can be
      divided into four different areas, each characterized by a specific set of
      efferent connections. To establish whether the different areas of the subiculum
      are similar with respect to the organization of the origin of their respective
      efferents, the double-fluorescence retrograde-tracing technique was used to study
      the degree of collateralization. Because CA1 gives rise to a major input to the
      subiculum but also projects to some of the targets reached by subicular
      projections, we compared the subicular degree of collateralization with that of
      CA1. Throughout CA1, the percentages of double-labeled cells were high, ranging
      from 17% to 39%. In contrast, the percentages of double-labeled cells in the
      subiculum were much lower, ranging from 0% to 12%, and no differences were noted
      between the four areas of the subiculum. This indicates that the four regions of
      the subiculum are organized in the same way with regard to the output
      connectivity. Because all four different regions of the subiculum share this
      paucity of collateralized projections, we conclude that subicular outputs
      generally originate as parallel projections. This characteristic organization is
      in line with a proposed function of the subiculum in information storage.

PMID- 9548549
TI  - Morphology of basal optic tract terminals in the turtle, Pseudemys scripta
      elegans.
AB  - The morphologies of axon terminals of retinal ganglion cells projecting to the
      basal optic nucleus (BON) via the basal optic tract (BOT) were studied in the red
      eared turtle. The BOT was visualized on the ventral surface of the brainstem in
      vitro, and either biotinylated dextran amine was injected extracellularly or
      neurobiotin was injected into physiologically identified axons during
      intracellular recordings. Up to 16 hours after tracer injection, the brains were
      fixed, sectioned parasagittally, and stained for biotin and Nissl substance. The
      diameters and depths of extracellularly filled axons were measured at three BON
      sites. Fourteen axons were reconstructed from serial sections with the aid of
      appropriate computer software. Analysis of extracellularly filled retinal axons
      revealed that about three times more axons were present just inside the rostral
      border of the BON compared with its caudal border. Thick (2-4 microm) axons were
      located within 100 microm from the ventral border, whereas thin (<2 microm) axons
      were found throughout the nucleus. Only the thinnest axons (<1 microm) extended
      caudally from the nucleus, indicating that some extracellularly labelled fibers
      passed through the BON. The intracellularly filled axons were more similar to the
      thick axons filled extracellularly and arborized entirely within the BON. All of
      the intracellularly filled axons had thick ventral trunks from which many thin
      branches extended dorsally and obliquely within the BON. The thin branches
      bifurcated repeatedly to form bead-like varicosities or boutons that often formed
      clusters within regions of 150 microm3 or less. These clusters may reflect areas
      of focused synaptic contact on BON cells with specific direction preferences.

PMID- 9548551
TI  - Spatial distributions of retinoic acid receptor gene transcripts in the prenatal
      mouse inner ear.
AB  - The expression patterns of the three mouse retinoic acid (RA) receptor gene
      isotypes (RARalpha, RARbeta, and RARgamma) and retinoid X receptor gene isotypes
      (RXRalpha, RXRbeta, and RXRgamma) have been investigated by in situ hybridization
      analysis of their RNA transcripts in the inner ear of mouse fetuses at 18.5 days
      of gestation. Two RARs (RARalpha and RARgamma) and two RXRs (RXRalpha and
      RXRbeta) presented an almost ubiquitous transcript distribution with overlapping
      expression in several regions of the cochlea, such as Kolliker's organ, the organ
      of Corti, the spiral limbus, and nervous structures. The organ of Corti showed an
      enhanced in situ labeling with RARalpha and RXRbeta. By contrast, RARbeta and
      RXRgamma displayed more restricted expression patterns. RXRgamma in particular
      was strongly expressed in Kolliker's organ and in the spiral ganglion. This
      expression pattern suggests that RA may be involved in the differentiation of
      several cochlear cell types. Moreover, the colocalization of several RAR and RXR
      gene transcripts suggests possible heterodimerization between these receptors in
      several regions of the cochlea.

PMID- 9548552
TI  - Gamma-aminobutyric acidA receptors on a bistratified amacrine cell type in the
      rabbit retina.
AB  - Gamma-Aminobutyric acid (GABA) is considered to be a major inhibitory
      neurotransmitter in the inner plexiform layer of the retinas of all vertebrate
      species. It is contained in and released from nearly 40% of the amacrine cells
      and is known to play a major role in many aspects of visual processing. By using
      well-characterized antibodies to several subunits of the GABA(A) receptor, we
      have analyzed their localization on the cell bodies and dendritic trees of two
      amacrine cell populations in the rabbit retina, which have been either filled
      intracellularly with Lucifer yellow or stained immunohistochemically. Both
      populations are selectively stained by intravitreal injection of the fluorescent
      nuclear dye 4',6-diaminidin-2-phenylindoldihydrochloride (DAPI). We have found
      that the most significant concentration of the alpha1 and beta2/3 GABA(A)
      receptor subunits is localized to the DAPI-3 type amacrine cell. The perikarya of
      the DAPI-3 cells are found in the proximal inner nuclear layer and send their
      processes into two sublayers in sublaminae a and b of the inner plexiform layer.
      These processes abut but do not directly overlap those of the two mirror
      symmetric populations of starburst amacrine cells. Because the cell bodies of the
      DAPI-3 cells are the only ones in the inner nuclear layer that stain strongly for
      either the alpha1 or beta2/3 subunits, such staining is a diagnostic feature of
      these cells. Their processes also constitute the most strongly staining ones
      found within the inner plexiform layer. The dendritic trees of DAPI-3 cells,
      which range from about 150 microm up to about 300 microm, exhibit recurvate
      looping processes reminiscent of those described for directionally selective
      ganglion cells. In contrast to the DAPI-3 cell, we have also shown that the
      starburst amacrine cells exhibit no immunoreactivity for the alpha1 GABA(A)
      receptor subunit and very little for the beta2/3 subunit. Thus, we have shown
      that the DAPI-3 cells contain the highest concentrations of the alpha1 and
      beta2/3 GABA(A) receptor subunits in the rabbit retina. These cells, which
      costratify near the processes of both the starburst amacrine cells and the ON-OFF
      directionally selective ganglion cells, thus, are situated both anatomically and
      by virtue of their receptor content to potentially interact.

PMID- 9548553
TI  - Developmental expression of alpha 9 acetylcholine receptor mRNA in the rat
      cochlea and vestibular inner ear.
AB  - Expression of alpha9 acetylcholine receptor (AChR) mRNA was studied by in situ
      hybridization in the rat adult and developing cochlea and vestibular inner ear.
      Alpha9 AChR mRNA was first observed in cochlear hair cells (HCs) at embryonic day
      18 (E18), increased markedly after birth, stayed high until postnatal day 10
      (P10), and decreased to substantially lower adult levels by P14. High levels of
      alpha9 AChR mRNA expression were also noted in the developing nonneuronal
      structures of the inner sulcus, chondrocytes, and/or osteoblasts in the cochlear
      capsule and interscalar laminae. Both developing and adult bone marrow cells also
      expressed intense alpha9 AChR mRNA. In the vestibular system, alpha9 AChR mRNA
      was first observed in HCs at E16 in all sensory epithelia, increased to its
      highest levels by P0-P4, then decreased slightly to reach adult levels by P10.
      The results are consistent with the alpha9 AChR subserving efferent
      neurotransmission to both cochlear and vestibular HCs. The observation of alpha9
      AChR mRNA in cochlear HCs 2 weeks prior to functional onset in the cochlea
      further suggests that expression of this gene is not related to HC activity. The
      observation of substantial nonneuronal expression of alpha9 AChR mRNA suggests
      that this receptor also has functions separate from its role in
      neurotransmission.

PMID- 9548555
TI  - Quantitative Golgi study of the rat cerebellar molecular layer interneurons using
      principal component analysis.
AB  - In this study, we applied for the first time a multivariate analysis to describe
      the anatomy of cerebellar molecular layer interneurons. Forty variables extending
      over a variety of morphological features (geometrical, topological, and metrical)
      were obtained from a three-dimensional reconstruction of 26 rat rapid Golgi
      stained neurons. The subsequent principal component analysis showed that the
      first principal component was strongly correlated with variables related to the
      depth of each cell's soma in the molecular layer. The second principal component
      was strongly correlated with parameters describing axonal morphology. Finally, an
      analysis of the distribution of these anatomical features suggested that these
      cells cannot be classified into distinct groups but, instead, represent one
      continuously varying population. Thus, the classical division of molecular layer
      neurons into deep basket cells and superficial stellate cells is not supported by
      our analysis. These results have important implications for the development of
      the cerebellar cortex as well as for the expected patterns of Purkinje cell
      activity following activation of the granule cell layer.

PMID- 9548554
TI  - Immunohistochemical localization of metabotropic glutamate receptors, mGluR7a and
      mGluR7b, in the central nervous system of the adult rat and mouse: a light and
      electron microscopic study.
AB  - The distributions of two alternative splicing variants of metabotropic glutamate
      receptor mGluR7, mGluR7a and mGluR7b, were examined immunohistochemically in the
      rat and mouse by using variant-specific antibodies raised against C-terminal
      portions of rat mGluR7a and human mGluR7b. Many regions throughout the central
      nervous system (CNS) showed mGluR7-like immunoreactivities (LI). The distribution
      patterns of mGluR7-LI in the rat were substantially the same as those in the
      mouse, although some species differences were observed in a few regions. Intense
      mGluR7a-LI was seen in the main and accessory olfactory bulbs, anterior olfactory
      nucleus, islands of Calleja, superficial layers of the olfactory tubercle,
      piriform cortex and entorhinal cortex, periamygdaloid cortex, amygdalohippocampal
      area, hippocampus, layer I of the neocortical regions, globus pallidus,
      superficial layers of the superior colliculus, locus coeruleus, and superficial
      layers of the medullary and spinal dorsal horns. The distribution of mGluR7b was
      more restricted. It was intense in the islands of Calleja, substantia innominata,
      hippocampus, ventral pallidum, and globus pallidus. The medial habenular nucleus
      also showed intense mGluR7a-LI in the rat but not in the mouse. For both mGluR7a-
      and mGluR7b-LI, localization in the active zones of presynaptic axon terminals
      was confirmed electron microscopically at synapses of both the asymmetrical and
      symmetrical types. It is noteworthy that mGluR7a-LI is seen preferentially in
      relay nuclei of the sensory pathways and that both mGluR7a- and mGluR7b-LI are
      observed not only in presumed glutamatergic axon terminals, but also in non
      glutamatergic axon terminals including presumed inhibitory ones. Thus, mGluR7 may
      play roles not only as an autoreceptor in glutamatergic axon terminals, but also
      as a presynaptic heteroreceptor in non-glutamatergic axon terminals in various
      CNS regions.

PMID- 9548556
TI  - Distribution of butyrylcholinesterase in the human amygdala and hippocampal
      formation.
AB  - The distribution of the major cholinergic regulatory enzyme acetylcholinesterase
      (AChE, EC 3.1.1.7) has been extensively studied in the human brain, but the
      distribution of the closely related enzyme butyrylcholinesterase (BuChE, EC
      3.1.1.8) is largely unknown. Because of the importance of BuChE and AChE in
      Alzheimer's disease, we have studied the distribution of BuChE in the normal
      human amygdala and hippocampal formation and compared it with that of AChE by
      using histochemical techniques. In the amygdala, the distribution of BuChE
      differed significantly from that of AChE in that BuChE was found primarily in
      neurons and their dendritic processes, whereas AChE was found predominantly in
      the neuropil. BuChE-positive neurons were present in up to 10% of the neuronal
      profiles in lateral, basolateral (basal), basomedial (accessory basal), central,
      cortical, and medial amygdaloid nuclei. AChE was found primarily in the neuropil
      in these nuclei with only a few AChE-positive neurons. In the hippocampal
      formation, BuChE was also found in neurons and not in the neuropil, whereas AChE
      was found in both neurons and in the neuropil. BuChE and AChE neurons were
      present in the polymorphic layer of the dentate gyrus, as well as the stratum
      oriens and stratum pyramidale of the hippocampus proper. There was considerable
      overlap in shapes, sizes, and numbers of BuChE- and AChE-positive neurons,
      suggesting that the enzymes were colocalized in neurons of the hippocampal
      formation. The distinct distribution of BuChE suggests that it may have specific
      functions including coregulation of cholinergic and noncholinergic
      neurotransmission in human amygdala and hippocampal formation.

PMID- 9548557
TI  - Synaptology of the direct projections from the nucleus of the solitary tract to
      pharyngeal motoneurons in the nucleus ambiguus of the rat.
AB  - During the pharyngeal phase of the swallowing reflex, the nucleus of the solitary
      tract (NTS) receives peripheral inputs from the pharynx by means of the
      glossopharyngeal ganglion and is the location of premotor neurons for the
      pharyngeal (PH) motoneurons. The semicompact formation of the nucleus ambiguus
      (AmS) is composed of small and medium-sized neurons that do not project to the
      pharynx, and large PH motoneurons. We investigated whether the neurons in the NTS
      projected directly to the PH motoneurons or to the other kinds of neurons in the
      AmS by using the electron microscope. When wheat germ agglutinin-conjugated
      horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin
      subunit B-conjugated HRP (CT-HRP) injections into the pharyngeal muscles of male
      Sprague-Dawley rats, many nerve terminals anterogradely labeled with WGA-HRP were
      found to contact PH motoneurons retrogradely labeled with CT-HRP. Most of the
      labeled axodendritic terminals (63%) contained pleomorphic vesicles with
      symmetric synaptic contacts (Gray's type II), and the remaining ones contained
      round vesicles with asymmetric synaptic contacts (Gray's type I). About 14% of
      the axosomatic terminals on PH motoneuron in a sectional plane were anterogradely
      labeled, and about 70% of the labeled axosomatic terminals were Gray's type II.
      Observations of serial ultrathin sections revealed that both the small and the
      medium-sized neurons received only a few labeled axosomatic terminals that were
      exclusively Gray's type I. These results indicate that the NTS neurons may send
      mainly inhibitory as well as a few excitatory inputs directly to the PH
      motoneurons in the AmS.

PMID- 9548558
TI  - Induction of interleukin (IL)-1 alpha and beta gene expression in human
      keratinocytes exposed to repetitive strain: their role in strain-induced
      keratinocyte proliferation and morphological change.
AB  - Recent studies in our laboratory have demonstrated that mechanical strain alters
      many facets of keratinocyte biology including proliferation, protein synthesis,
      and morphology. IL-1 is known to play an important role in the autocrine
      regulation of these basic cellular properties under basal and stimulated
      conditions. However, it is not known whether IL-1 plays a role in strain-induced
      alteration of keratinocyte biology. Thus, the objective of this study was to test
      the hypothesis that cyclic strain stimulates IL-1 expression and that strain
      induced changes in keratinocyte function is regulated by IL-1. To test this
      hypothesis, we examined the effect of cyclic strain (10% average deformation) on
      keratinocyte IL-1 gene expression and the effect of neutralizing antibodies of IL
      1 alpha and IL-1 beta on strain-induced changes in keratinocyte proliferation,
      morphology, and orientation. Northern blot analyses demonstrated that steady
      state levels of IL-1 alpha and beta mRNA were elevated by 4 h, peaked at 1 2 h of
      cyclic strain (IL-1 alpha, 304+/-14.2%; IL-1 beta, 212+/-5.6% increase vs. static
      controls) and decreased gradually by 24 h. IL-1 antibodies (IL-1 alpha, 0.01
      microg/ml; IL-1 beta, 0.01 microg/ml) significantly blocked strain-induced
      keratinocyte proliferation as well as the basal rate of proliferation. In
      contrast, IL-1 antibodies (IL-1 alpha, 0.01 microg/ml; IL-1 beta, 0.1 microg/ml)
      had no effect on strain-induced morphological changes such as elongation and
      alignment. We conclude that mechanical strain induces IL-1 mRNA expression in
      keratinocytes. The role of IL-1 in mediating strain-induced changes in
      keratinocyte biology remains to be determined but appears to be independent of
      morphological changes.

PMID- 9548559
TI  - Pre-mRNA processing enhancer (PPE) element increases the expression of an
      intronless thymidylate synthase gene but does not affect intron-dependent S phase
      regulation.
AB  - The pre-mRNA processing enhancer (PPE) element is an RNA sequence element derived
      from the intronless HSV-TK gene. Insertion of the element into the highly intron
      dependent human beta-globin gene leads to efficient expression in the absence of
      splicing. We have analyzed the effect of the PPE element on the expression of
      mouse thymidylate synthase (TS) minigenes. We have previously shown that the
      expression of intronless TS minigenes is moderately (up to 20-fold) stimulated by
      the inclusion of introns. Furthermore, S phase-specific expression of TS
      minigenes in growth-stimulated cells depends on the presence of a spliceable
      intron as well as the TS promoter. The goal of our study was to determine if the
      PPE element would overcome the dependence on introns for efficient expression and
      for S phase-specific expression of transfected TS minigenes. We found that
      insertion of the PPE element into an intronless TS minigene partially overcame
      intron dependence. However, the increase in expression was much less than that
      observed for the intronless beta-globin gene. We also found that intronless TS or
      HSV-TK genes that contained the PPE element and that were driven by the TS
      promoter were expressed at a constant level in serum-stimulated cells. However,
      when an intron was included in these genes, they were expressed in an S phase
      specific manner. Thus the PPE element was not able to overcome the dependence on
      introns for S phase-specific expression of TS minigenes.

PMID- 9548560
TI  - The haemochromatosis candidate gene HFE (HLA-H) of man and mouse is located in
      syntenic regions within the histone gene cluster.
AB  - The HFE (HLA-H) gene is a strong candidate gene for hereditary haemochromatosis
      and was localized on the short arm of chromosome 6 to 6p21.3-p22. In addition,
      the sequence of the homologous mouse and rat cDNA and a partial sequence from the
      mouse gene have been reported recently. In this report, we describe the location
      of the human and the mouse HFE (HLA-H) gene within the histone gene clusters on
      the human chromosome 6 and the mouse chromosome 13. Both the human and the murine
      gene were located on syntenic regions within the histone gene clusters in the
      vicinity of the histone H1t gene. The genomic sequence of the human HFE (HLA-H)
      gene and the 3' portion of the homologous mouse gene were determined. Comparison
      of the genomic sequences from man and mouse and the cDNA sequence from rat shows
      significant similarities, also beyond the transcribed region of the mouse gene.

PMID- 9548561
TI  - DNA topoisomerase II can drive changes in higher order chromosome architecture
      without enzymatically modifying DNA.
AB  - Topoisomerase II has been suggested to play a major role in chromosome
      organization based on its DNA decatenating activity and its ability to mediate
      direct binding interactions between DNA and nuclear matrix. However, this latter
      point remains controversial. Here we address the question of whether the
      chromatin binding activity of Topoisomerase II is sufficient to modify chromosome
      form using whole mammalian chromosomes in vitro. Intact chromosomes were
      microsurgically removed from living cells and disassembled by treatment with
      protease or heparin. When these disassembled chromosomes were incubated with
      recombinant human Topoisomerase II, the enzyme became incorporated into chromatin
      and reassembly resulted, leading to almost complete restoration of pre-existing
      chromosome shape and position within minutes. Chromosome reconstitution by
      Topoisomerase II was dose-dependent, saturable, and appeared to be controlled
      stoichiometrically, rather than enzymatically. Similar reassembly was observed in
      the absence of ATP and when a catalytically inactive thermosensitive
      Topoisomerase II mutant was used at the restrictive temperature. Chromosome
      recondensation also could be induced after the strand-passing activity of
      Topoisomerase II was blocked by treatment with an inhibitor of its catalytic
      activity, amsacrine. When a non-hydrolyzable beta,gamma-imido analog of ATP (AMP
      PNP) was used to physiologically fix bound Topoisomerase II enzyme in a closed
      form around DNA, subsequent chromosome disassembly was prevented in the presence
      of high salt. These data suggest that Topoisomerase II may control higher order
      chromatin architecture through direct binding interactions, independently of its
      well-known catalytic activity.

PMID- 9548562
TI  - Extracellular calcium influx stimulates metalloproteinase cleavage and secretion
      of heparin-binding EGF-like growth factor independently of protein kinase C.
AB  - The phorbol ester, tetradecanoyl-phorbol 13-acetate (TPA), stimulates rapid
      proteolytic processing of the transmembrane, pro- form of heparin-binding
      epidermal growth factor-like growth factor (HB-EGF) at cell surfaces, suggesting
      the involvement of protein kinase C (PKC) isoforms in the HB-EGF secretion
      mechanism. To test this possibility, we expressed a chimeric protein, consisting
      of proHB-EGF fused to placental alkaline phosphatase (AP) near the amino terminus
      of processed HB-EGF, in NbMC-2 prostate epithelial cells. The proHB-EGF-AP
      chimera localized to plasma membranes and functioned as a diphtheria toxin
      receptor. Secreted HB-EGF-AP bound to heparin and exhibited potent growth factor
      activity. The presence of the AP moiety allowed highly quantitative measurements
      of cleavage-secretion responses of proHB-EGF to extracellular stimuli. As
      expected, rapid secretion of HB-EGF-AP was induced in a time- and dose-dependent
      manner by TPA. However, this was also observed with the Ca2+ ionophore,
      ionomycin, suggesting the involvement of extracellular Ca2+ ions in the secretion
      mechanism. Ionomycin-induced secretion was inhibited by extracellular calcium
      chelation but not by the PKC inhibitors, GF109203X, staurosporine, or
      chelerythrine. The TPA-mediated secretion effect was inhibited by staurosporine,
      GF109203X, and by pretreatment with TPA, but not by calcium chelation. A small
      secretion response was induced by thapsigargin, which releases Ca2+ from
      intracellular stores, but this was completely eliminated by extracellular calcium
      chelation. Ionomycin- and TPA-induced HB-EGF-AP secretion was not dependent on
      the presence of the proHB-EGF cytoplasmic domain and was specifically inhibited
      by the metalloproteinase inhibitors 1,10-phenanthroline and tissue inhibitor of
      metalloproteinase-1 (TIMP-1). These data demonstrate that extracellular Ca2+
      influx activates a membrane-associated metalloproteinase to process proHB-EGF by
      a pathway that does not require PKC.

PMID- 9548563
TI  - Multiple levels of steroid hormone-dependent control of osteocalcin during
      osteoblast differentiation: glucocorticoid regulation of basal and vitamin D
      stimulated gene expression.
AB  - We have examined the contribution of transcriptional mechanisms to the
      pleiotropic effects of glucocorticoids on basal and vitamin D stimulated
      expression of the developmentally regulated bone-specific osteocalcin (OC) gene.
      OC expression was systematically investigated at the level of protein, mRNA, and
      newly synthesized transcripts during maturation of the bone cell phenotype in
      cultures of fetal rat calvarial-derived osteoblasts. Our results indicate that
      transcriptional control of basal and hormone-regulated OC expression predominates
      in immature osteoblasts prior to matrix mineralization. However, in mature
      osteoblasts OC expression is controlled primarily by posttranscriptional
      mechanisms reflected by elevated mRNA levels with a decline in transcription.
      Vitamin D, alone or in combination with Dex, is a significant factor contributing
      to mRNA stabilization in mature osteoblasts with a mineralized extracellular
      matrix. Transcriptional modifications in response to Dex are reflected by
      quantitative differences between proliferating and mature osteoblasts in the
      formation of glucocorticoid receptor binding complexes at the proximal OC
      glucocorticoid response element. Vitamin D and glucocorticoid receptor mRNA
      levels are significantly higher in mature osteoblasts than in early stage bone
      cells. However, receptor complexes do not appear to be rate limiting in
      proliferating osteoblasts when the OC gene is not transcribed. Our results
      indicate (1) developmental stage-specific effects of steroid hormone on
      transcriptional regulation of bone expressed genes, and (2) inverse relationships
      between levels of transcription and cellular representation of mRNA with OC
      message stabilized in mature osteoblasts.

PMID- 9548564
TI  - Pulse application of platelet-derived growth factor enhances formation of a
      mineralizing matrix while continuous application is inhibitory.
AB  - Platelet-derived growth factor (PDGF) stimulates chemotaxis and proliferation of
      osteoblasts, and induces bone formation in vivo. To determine how PDGF might
      regulate these cells, the effect of PDGF on long-term mineralizing cultures of
      fetal rat osteoblastic cells was examined. Although PDGF increased cell
      proliferation in these cultures, continuous treatment with PDGF caused a dose
      dependent decrease in mineralized nodule formation. When cells were treated with
      multiple, brief (1 day) exposures to PDGF at the osteoblast differentiation
      stage, there was a significant 50% increase in mineralized nodule area. Based on
      modulation of alkaline phosphatase activity it appears that longer-term exposure
      to PDGF reduces mineralized nodule formation largely by inhibiting differentiated
      osteoblast function, while short-term exposure enhances proliferation without
      inhibiting the differentiated phenotype. Thus, the ultimate affect of PDGF on
      bone formation is likely to reflect two processes: a positive effect through
      enhancing cell number or a negative effect by inhibiting differentiated function.
      The inhibitory effect of PDGF on formation of a mineralized matrix is unlikely to
      be simply a result of enhanced proliferation of "fibroblastic" cells since
      cultures treated with PDGF for 3 days and then transferred to new plastic dishes
      exhibited a 70% increase in mineralized nodule area compared to controls. These
      results would predict that multiple, brief exposures to PDGF would enhance bone
      formation in vivo, while prolonged exposure to PDGF, which is likely to occur in
      chronic inflammation, would inhibit differentiated osteoblast function and limit
      bone regeneration.

PMID- 9548565
TI  - Myc-mediated transactivation of HSP70 expression following exposure to magnetic
      fields.
AB  - We investigated c-myc protein-binding sites on the HSP70 promoter as modulators
      of the induction of HSP70 gene expression in response to magnetic field
      stimulation (8microT at 60Hz) and whether the presence of c-myc protein
      potentiates transactivation of HSP70 expression. A 320 base pair region in the
      HSP70 promoter (+1 to -320) was analyzed. This region contains two c-myc-protein
      binding sites with consensus sequences located at -230 and -160 nucleotide
      positions (relative to the transcription initiation site) and overlapping with
      the region reported for the regulation of HSP70 gene expression by c-myc protein.
      This promoter region is upstream of other regulatory sequences, including the
      heat shock element (HSE), AP-2, and serum response element (SRE). Transfectants
      containing both c-myc protein-binding sites, HSP-MYC A and HSP-MYC B, and exposed
      to magnetic fields showed a 3.0-fold increase in expression of CAT activity as
      compared with sham-exposed control transfectants. Transfectants containing one c
      myc binding site, HSP-MYC A, and exposed to magnetic fields showed a 2.3-fold
      increase in CAT expression. Transfectants in which both HSP-MYC A and HSP-MYC B
      binding sites were deleted showed no magnetic field sensitivity; values were
      virtually identical with sham-exposed controls. If the c-myc expression vector
      was not co-transfected with the constructs containing myc-binding sites, there
      was no difference in the expression of CAT activity between magnetically
      stimulated and sham-exposed controls, although both responded to heat shock.
      These data suggest that endogenous elevated levels of myc protein contribute to
      the induction of HSP70 in response to magnetic field stimulation.

PMID- 9548566
TI  - Inhibition of PPAR alpha/RXR alpha-mediated direct hyperplasia pathways during
      griseofulvin-induced hepatocarcinogenesis.
AB  - Chronic griseofulvin (GF) feeding induces preneoplastic foci followed by
      hepatocellular carcinoma in the mouse liver. Our previous study suggested that GF
      induced hepatocellular proliferation had a different mechanism from that of
      peroxisome proliferator (PP)-induced direct hyperplasia. The GF-induced
      hepatocellular proliferation was mediated through activation of immediate early
      genes such as Fos, Jun, Myc, and NFKB. In contrast, PP-induced direct hyperplasia
      does not involve activation of any of these immediate early genes. It has been
      shown that nuclear hormone receptors including peroxisome proliferator activated
      receptors (PPARs) and retinoid x receptors (RXRs) play important roles in
      mediating the pleiotropic effects of PPs. To examine the possible roles of PPARs
      and RXRs during non-PP-induced hepatocellular proliferation and the interaction
      between PP and non-PP-induced proliferation, we have studied the expression of
      the PPAR and RXR genes in the GF model using northern blot hybridizations and gel
      retardation assays. The data showed that the expression of PPARalpha and RXRalpha
      genes was down-regulated in the livers containing preneoplastic nodules and in
      the liver tumors induced by GF. The mRNA down-regulation was accompanied by a
      decrease in the amount of nuclear protein-bound to peroxisome proliferator and
      retinoic acid responsive elements. Down-regulation was also associated with the
      suppressed expression of the PPARalpha/RXRalpha target genes (i.e., acyl-Co
      oxidase and cytochrome P450 4A1) and the catalase gene. The RXR-gamma gene was
      also down-regulated, but the RARalpha, beta, and gamma and PPARbeta and gamma
      genes were up-regulated. These results indicated that the hepatocarcinogenesis
      induced by GF is accompanied by suppression of the PPARalpha/RXRalpha-mediated
      direct hyperplasia pathway. The differential expression of these nuclear hormone
      receptors reveals a new aspect for understanding the individual roles and
      intercommunication of PPAR, RXR, and RAR isoforms in the liver.

PMID- 9548567
TI  - Effect of sodium butyrate on the expression of genes transduced by retroviral
      vectors.
AB  - We have studied the effects of sodium butyrate (NaBu) on the expression of genes
      transduced by retroviral vectors and stably expressed in two salivary gland
      derived cell lines, A5-DAP and A5-BAG, established earlier. These cell lines were
      obtained by infecting A5 cells with the retroviral vectors DAP and BAG,
      respectively, and by selecting neomycin-resistant transduced cells. A5-DAP cells
      express human placental alkaline phosphatase (PLAP) and A5-BAG cells bacterial
      beta-galactosidase, both under the control of the viral long terminal repeat
      (LTR) enhancer-promoter. NaBu in the concentration of 2-8 mM inhibited the growth
      of A5-DAP cells, and induced the expression of heat-stable PLAP. These effects of
      NaBu were dose-dependent. Induction of PLAP in clones of A5-DAP cells that
      express different basal levels of the enzyme was not correlated with the relative
      inducibilty by NaBu. Exposure to 4 mM NaBu for 48 h increased the PLAP mRNA level
      by 31%. A5-DAP cells released, in a time-dependent manner, PLAP into the culture
      medium. Cells treated with NaBu released more PLAP than untreated cells in
      proportion to their elevated level of the enzyme. The parent A5 cells also
      express a low level of tissue non-specific type alkaline phosphatase, which was
      also induced by NaBu. NaBu inhibited the growth of A5-BAG cells also, and
      increased the beta-galactosidase level. These data indicate the genes transduced
      by retroviral vectors can be induced by NaBu, which most likely interacts with
      the viral LTR.

PMID- 9548568
TI  - Mechanism of protein kinase CK2 association with nuclear matrix: role of
      disulfide bond formation.
AB  - Nuclear matrix (NM) appears to be an intranuclear locale for significant and
      dynamic association of the ubiquitous multifunctional messenger-independent
      serine/threonine protein kinase CK2 that has been implicated in growth control
      [Tawfic et al. (1996): J Cell Biochem 61:165-171]. We have examined the nature of
      the association of CK2 with the NM. Nuclei prepared in the presence of a
      sulfhydryl-blocking reagent such as iodoacetamide demonstrate a reduction in the
      amount of CK2 associated with the NM to less than 5% of the control. On the other
      hand, when nuclei are treated with the sulfhydryl crosslinking reagent sodium
      tetrathionate, NM-associated CK2 increases severalfold. Treatment of nuclei with
      sodium tetrathionate followed by 2-mercaptoethanol blocks this increase. Nuclei
      isolated from rat liver and prostate behaved similarly, suggesting an identical
      mode of association of CK2 with the NM regardless of the organ. These results
      indicate a role of sulfhydryl interactions such that NM anchoring of CK2 occurs
      via its beta subunit, which contains several vicinal cysteine residues. Further,
      various sulfhydryl-blocking reagents inhibited CK2 activity in a concentration
      dependent manner, and the inhibitory effect was reversed by agents such as
      dithiothreitol, implying that cysteine residues in the CK2 play a role in its
      catalytic activity.

PMID- 9548569
TI  - Induction of stress response and differential expression of 70 kDa stress
      proteins by sodium fluoride in HeLa and rat brain tumor 9L cells.
AB  - We herein demonstrate that sodium fluoride (NaF) acts as a stress response
      inducer on HeLa and 9L rat brain tumor cells. NaF is only slightly cytotoxic, and
      inhibitory to Ser/Thr-phosphatases but not to Tyr-phosphatases in both cell
      lines. After treatment with 5 mM NaF for 2 h, the phosphorylation levels of
      vimentin and an alkali-resistant 65-kDa phosphoprotein were enhanced, a common
      phenomenon detected in cells under a variety of stress conditions. Under an
      identical treatment protocol, in which the cells were treated with 5 mM NaF for 2
      h and then allowed to recover under normal growing conditions for up to 12 h, NaF
      differentially induced the cytoplasmic/nuclear heat-shock protein70s (including
      both the inducible and the constitutively expressed members of this protein
      family) in HeLa cells and the endoplasmic reticulum residing heat-shock protein70
      (the glucose-regulated protein with an apparent molecular weight of 78 kDa) in 9L
      cells. Electrophoretic mobility shift assays (EMSA) using probes containing well
      characterized regulatory elements revealed the activation of the heat-shock
      factor in HeLa but not in 9L cells; this is in good agreement with the stress
      protein induction pattern. Additional differential induction of binding
      activities toward EMSA probes individually containing NF-KB, AP-2, and CRE-like
      elements were detected in NaF-treated cells. The possible involvement of these
      binding sites as well as the corresponding factors in the stress response are
      discussed.

PMID- 9548570
TI  - Macular hole.
AB  - A macular hole is a full-thickness defect of retinal tissue involving the
      anatomic fovea, thereby affecting central visual acuity. Macular holes have been
      associated with myriad ocular conditions and originally were described in the
      setting of trauma. The pathogenesis of idiopathic, age-related macular holes
      remains unclear despite a litany of theories. Recently, Gass has described an
      updated biomicroscopic classification of macular holes and postulated that
      tangential vitreous traction may play a role. Cellular components surrounding the
      rim of macular holes may also contribute tangential traction forces and elevate
      the rim. Pseudomacular holes may be mistaken for macular hole lesions, despite
      careful clinical examination. Careful biomicroscopic examination with a contact
      lens and use of the Watzke and laser aiming beam tests help to ensure accurate
      diagnosis. Newer imaging technology, such as optical coherence tomography, helps
      distinguish true macular holes from pseudoholes and may provide additional
      insight into the pathogenesis of this condition. Surgical management with or
      without pharmacosurgical adjuncts can improve vision in select cases. The most
      common surgical complication is progressive lens opacification in phakic
      patients.

PMID- 9548571
TI  - Intraocular lens complications requiring removal or exchange.
AB  - Intraocular lens (IOL)-related complications are caused primarily by mechanical
      trauma, inflammatory or infectious complications, or optical problems.
      Complications may occur at the time of surgery or be the result of an ongoing
      postoperative process. Mechanical and inflammatory injury may produce corneal
      decompensation, cystoid macular edema, hyphema, uveitis, and glaucoma, causing
      reduced vision and in some cases chronic pain. Optical problems may be due to a
      wrong power of the IOL or to postoperative decentration or dislocation of the
      lens. Ophthalmologists should be aware of the indications for IOL removal or
      exchange in those patients who have ongoing IOL-induced injury or impairment.
      Removal or exchange of an IOL frequently involves a complex decision-making
      process and is often associated with immense technical challenge. Various medical
      and surgical treatments may be tried to correct IOL problems before the decision
      is made to remove or exchange the lens.

PMID- 9548573
TI  - The vanishing of the sun: a manifestation of cortical plasticity.
AB  - In Monet's painting impression. Rising Sun, when one steadily fixates the image
      of a sailor in the center of the picture for several seconds, the solar disk
      progressively disappears, being replaced in both brightness and color by the
      surrounding sky. This "filling-in" phenomenon reflects a process of cortical
      remapping, similar to the one that occurs in the presence of visual field
      defects. Filling-in is largely ignored by clinicians, despite its major
      implications in ophthalmologic practice, especially the nonrecognition of visual
      field deficits.

PMID- 9548572
TI  - Double choroidal malignant melanoma in an eye with apparent clinical regression.
AB  - Multicentric melanomas in the same eye are rare, with few cases substantiated by
      histology and serial sectioning. We report a patient with two documented
      choroidal malignant melanomas in one eye. The initial tumor spontaneously
      decreased in size for over 2 years before a second tumor appeared in a
      noncontiguous location in the same eye. After enucleation, serial sections showed
      that the two lesions were independent choroidal melanomas. We review the
      literature regarding multiple, independent intraocular choroidal malignant
      melanomas.

PMID- 9548574
TI  - Visual loss after coronary artery bypass surgery.
AB  - A 70-year-old man underwent coronary artery bypass graft complicated
      postoperatively by visual loss. The diagnosis was nonarteritic anterior ischemic
      optic neuropathy. Possible predisposing factors in this patient were hypotension,
      anemia, a "disk at risk," and internal carotid artery stenosis. In the
      postoperative setting, the erythrocyte sedimentation rate may be elevated, as it
      was in this case and does not by itself suggest a diagnosis of giant cell
      arteritis.

PMID- 9548575
TI  - Wegener's granulomatosis.
AB  - Clinical manifestations of Wegener's granulomatosis are nonspecific and
      indistinguishable from a variety of neoplastic, infectious, and inflammatory
      diseases. Ophthalmic disease is the presenting feature in nearly one sixth of
      patients with Wegener's granulomatosis and will ultimately develop in a majority.
      The discovery of antineutrophil cytoplasmic antibodies, particularly
      antiproteinase-3, has changed the clinical approach to evaluating patients
      suspected of having Wegener's granulomatosis. These antibodies are distinguished
      from other related autoantibodies because they produce a coarse granular pattern
      of cytoplasmic staining on indirect immunofluorescence with ethanol-fixed
      neutrophils. Treatment of Wegener's granulomatosis with oral cyclophosphamide and
      corticosteroids has decreased morbidity and improved survival, but side effects
      from long-term immunosuppressive therapy are common and sometimes serious. The
      effectiveness of trimethoprim-sulfamethoxazole in decreasing the number and
      severity of recurrences of Wegener's granulomatosis is being investigated. It
      remains to be determined if wide use of trimethoprim-sulfamethoxazole in limited
      Wegener's granulomatosis could further improve the quality of life for some
      patients.

PMID- 9548576
TI  - Was Dom Perignon really blind?
AB  - Many sources perpetuate the tripartite myth that Dom Perignon was the blind
      inventor of champagne, whose senses of taste and smell were enhanced by his loss
      of vision. This myth, however, is seemingly contradicted by historical fact. Not
      only do ancient references suggest that sparkling wine existed long before
      Perignon's time, but the making of champagne was a scientific process that
      required careful measuring, weighing, and record keeping, and it is unlikely that
      Perignon was blind when he was perfecting champagne. While the truth regarding
      Dom Perignon's blindness has disappeared during the more than two and a half
      centuries since his death, it is interesting to speculate why he may have lost
      vision at some stage of life. A brief history of Perignon's discovery of the
      secret of champagne and the blindness myth is traced, and a differential
      diagnosis is given, including cataracts, uncorrected refractive error, alcohol
      toxicity, and champagne-related ocular/cerebral trauma.

PMID- 9548577
TI  - Hypothesis: septo-optic dysplasia is a vascular disruption sequence.

PMID- 9548578
TI  - Variations in cataract extraction rates in Medicare prepaid and fee-for-service
      settings.

PMID- 9548579
TI  - Visual symptoms after optic neuritis: results from the Optic Neuritis Treatment
      Trial.

PMID- 9548580
TI  - An additional article on Rosenbaum cards.

PMID- 9548581
TI  - Fatty acid transport: difficult or easy?
AB  - Transport of unesterified fatty acids (FA) into cells has been viewed either as a
      simple diffusion process regulated mainly by lipid physical chemistry or as a
      more complex process involving protein catalysis. In this review FA transport in
      cell membranes is broken down into three essential steps: adsorption,
      transmembrane movement, and desorption. The physical properties of FA in aqueous,
      membrane, and protein environments relevant to transport mechanisms are
      discussed, with emphasis on recent information derived from NMR and fluorescence
      studies. Because of their low solubility in water and high hydrophobicity, FA
      bind rapidly and avidly to model membranes (phospholipid bilayers); if albumin is
      a donor, FA desorb rapidly to reach their equilibrium distribution between the
      membrane and albumin. The ionization properties of FA in a phospholipid bilayer
      result in a high population of the un-ionized form (approximately 50%) at pH 7.4,
      which diffuses across the lipid bilayer (flip-flops) rapidly (t(1/2) < 1 sec).
      Desorption of FA from a phospholipid surface is slower than transmembrane
      movement and dependent on the FA chain length and unsaturation, but is rapid for
      typical dietary FA. These physical properties of FA in model systems predict that
      proteins are not essential for transport of FA through membranes. The only
      putative FA transport protein to be purified and reconstituted into phospholipid
      bilayers, the mitochondrial uncoupling protein (UCP1), was shown to transport the
      FA anion in response to FA flip-flop. New experiments with cells have found that
      FA movement into cells acidifies the cytosol, as predicted by the flip-flop
      model.

PMID- 9548582
TI  - Isolation of macrophage-like cell mutants resistant to the cytotoxic effect of
      oxidized low density lipoprotein.
AB  - A high concentration of oxidized low density lipoprotein (Ox-LDL) showed a
      cytotoxic effect on mouse macrophage-derived J774 cells. Mutant cells were
      selected from these cells that were resistant to the cytotoxic effect of Ox-LDL.
      One mutant form, named JO21b cells, was characterized in the present study. In
      spite of a marked resistance to the cytotoxic effect of Ox-LDL, JO21b cells were
      apparently as sensitive as the parent cells not only to toxic moieties of Ox-LDL,
      such as 7-ketocholesterol and lysophosphatidylcholine, but also to t-butyl
      hydroperoxide, an artificial lipid hydroperoxide analog. However, the cellular
      association of 125I-labeled Ox-LDL with, and subsequent endocytic degradation by
      JO21b cells was reduced by 70-80% compared with J774 cells. Similarly,
      accumulation of cholesteryl esters in JO21b cell by Ox-LDL was also reduced by
      70%. Northern blot analyses of type I and type II macrophage scavenger receptors
      (type I and type II MSR) demonstrated that the mRNA levels of JO21b cells were
      lower than those of J774 cells. Moreover, peritoneal macrophages obtained from
      MSR-knockout mice showed a higher resistance to the cytotoxic effect of Ox-LDL
      than those from their wild-type littermates. Our results suggest, therefore, that
      macrophage scavenger receptor-mediated endocytic uptake of oxidized low density
      lipoproteins (Ox-LDL) may play an enhancing role in Ox-LDL cytotoxicity to
      macrophages or macrophage-derived cells.

PMID- 9548583
TI  - Temporal and spatial pattern of expression of the HDL receptor SR-BI during
      murine embryogenesis.
AB  - During rodent fetal development, maternal lipoproteins can be sources of
      cholesterol for the membrane synthesis required for tissue growth in the
      developing embryo and for steroid hormone production in the extraembryonic
      tissues. Although the mechanisms underlying the maternal-fetal lipoprotein
      cholesterol transport system are not well defined, the placenta and yolk sac seem
      to play major roles in this process, serving as functionally active interfaces
      between maternal circulation and the embryo. In rodents, the principal
      cholesterol transporter in the plasma is HDL, and the HDL receptor SR-BI is a
      physiologically important mediator of cholesterol uptake in adult liver and
      steroidogenic tissues. To begin to investigate SR-BI's role in maternal
      cholesterol uptake by the fetus, we used immunofluorescence microscopy to
      determine the pattern of SR-BI expression during murine embryogenesis. At day
      E7.5 in gestation, there was significant SR-BI expression in endothelial cells of
      the decidua, but little in intraembryonic and extraembryonic tissues. By day
      E8.5, there was a dramatic increase in SR-BI expression in the trophoblast cells
      which surround the developing embryo. Beginning at day E10, SR-BI was expressed
      in both the placenta and yolk sac. The expression in these extraembryonic tissues
      was correlated with significant uptake of fluorescent dye by the yolk sac
      visceral endodermal cells from DiI-labeled HDL injected into pregnant mice.
      Within the embryo proper, SR-BI expression appeared by day E14.5 at high levels
      in the adrenal gland. SR-BI expression was not detected in the embryonic liver
      through day E17.5 of gestation; however, it could be observed in neonatal livers.
      These findings suggest that SR-BI may play a role in the rodent maternal-fetal
      lipoprotein cholesterol transport system, supplying HDL cholesterol for either
      membrane or steroid hormone synthesis, or both.

PMID- 9548584
TI  - Alternative pre-mRNA splicing of the sterol 27-hydroxylase gene (CYP 27) caused
      by a G to A mutation at the last nucleotide of exon 6 in a patient with
      cerebrotendinous xanthomatosis (CTX).
AB  - A recently identified G to A mutation at the last nucleotide of exon 6 of the
      sterol 27-hydroxylase gene (CYP 27) in a patient with cerebrotendinous
      xanthomatosis (CTX) was shown here to cause alternative pre-mRNA splicing of the
      gene. Northern blot analysis of the patient's RNA revealed a broadened band in
      the human CYP 27 mRNA region compared to that of the normal sample, indicating
      that there may exist differently spliced mRNA species in the patient. RT-PCR
      produced three fragments in the patient, one was full-length size and the other
      two were of smaller sizes. Sequence analysis confirmed that the nucleotide of the
      full-length size was identical to that of the normal full-length cDNA, except for
      the G to A mutation at codon 362, which corresponds to the last nucleotide of
      exon 6. One of the smaller size species lacked exon 6 and the other was absent
      from the 3' terminal 88 bp of exon 6 due to the use of an activated cryptic 5'
      splice site in exon 6. The correctly spliced mRNA harbouring the G to A mutation
      was responsible for the deficiency of the sterol 27-hydroxylase activity, as
      confirmed by transfection experiment. Transfection of constructed minigenes, with
      or without the mutation, showed that correctly spliced mRNA was observed in the
      normal minigene while the mutant minigene was differently spliced. This is the
      first report of a G to A substitution at the last nucleotide of an exon resulting
      in both normal and abnormal pre-mRNA splicings, including exon skipping and
      activating of a coding region cryptic 5' splice site. The results reveal a new
      molecular basis for the CTX and provide information on aberrant splicing of pre
      mRNA in multi-exon genes.

PMID- 9548585
TI  - Transport of maternal LDL and HDL to the fetal membranes and placenta of the
      Golden Syrian hamster is mediated by receptor-dependent and receptor-independent
      processes.
AB  - Maternal lipoproteins provide nutrients to the fetus via the placenta, yolk sac,
      and uterine membrane plus decidua. To determine the transport processes that are
      responsible for the removal of lipoproteins from the maternal circulation, we
      measured the clearance rates of maternal LDL and HDL in vivo, as well as the
      tissue distribution of expression of the LDL receptor, glycoprotein 330 (gp330)
      and the newly described HDL receptor, SR-BI, in the placenta, yolk sac, and
      uterine membrane plus decidua at mid- and late-gestation of the hamster. In mid
      gestation (day 10.5), LDL clearance rates of the placenta and yolk sac were
      similar to those in the liver (approximately 100 microl/h per g) and higher than
      those in the decidua (18 +/- 3 microl/h per g). Clearance rates for HDL-apoA-I
      and HDL-cholesteryl ether were similar to those of LDL in the placenta and
      decidua whereas rates in the yolk sac were dramatically higher (>1700 microl/h
      per g). Additionally, albumin was cleared in the placenta and decidua at
      approximately 16 microl/h per g whereas the yolk sac cleared the protein at much
      higher rates (196 +/- 22 microl/h per g). Low levels of LDL receptor were
      detected by immunoblot analysis in the placenta with trace amounts in the yolk
      sac. Gp330 and SR-BI were both barely detectable in the placenta but were
      expressed at high levels in the yolk sac. As gestation progressed to day 14.5,
      LDL and HDL clearance rates decreased in all three tissues; immunodetectable LDL
      receptor decreased in the placenta whereas the expression of gp330 and SR-BI in
      the placenta and yolk sac remained relatively constant. These data suggest that
      the clearance of maternal lipoproteins by the placenta, yolk sac, and decidua are
      mediated by receptor-mediated as well as receptor-independent processes.

PMID- 9548586
TI  - A naturally occurring isoform of the human macrophage scavenger receptor (SR-A)
      gene generated by alternative splicing blocks modified LDL uptake.
AB  - The class A macrophage scavenger receptors (SR-A) are macrophage-specific
      trimeric integral membrane glycoproteins that have been implicated in many
      macrophage-associated physiological and pathological processes including
      atherosclerosis, Alzheimer's disease, and host defense. There are two forms of
      the receptor that have been previously cloned, and both are generated by
      alternative splicing of a single gene. Here we report the cloning of a third,
      alternatively spliced isoform of the human SR-A gene (type III hSR-A). The novel
      isoform is expressed in the human monocytic leukemia cell line THP-1 and also in
      primary human monocyte derived macrophages. When expressed in CHO-K1 cells, type
      III hSR-A does not internalize AcLDL despite having the domain shown to mediate
      this function in type I and II hSR-A. We show that type III protein has altered
      intracellular processing and is trapped within the endoplasmic reticulum, making
      it unable to perform endocytosis. Type III protein acts as a dominant negative
      isoform by reducing modified LDL uptake in CHO cells stably expressing either
      type I or type II SR-A. The demonstration that a naturally occurring splice
      variant of SR-A mRNA can act as a dominant negative isoform suggests a novel
      mechanism for regulation of scavenger receptor activity in macrophages.

PMID- 9548587
TI  - Cholesterol transport between cells and high density lipoprotein subfractions
      from obese and lean subjects.
AB  - We studied the pathway of cholesterol efflux from fibroblasts by testing plasma
      samples from obese and lean subjects. Plasma samples were incubated with
      [3H]cholesterol-labeled human skin fibroblasts for 1 h to ensure uniform labeling
      of all of the high density lipoprotein (HDL) subfractions. Supernatants were then
      transferred to unlabeled cells and the displacement of labeled cholesterol within
      HDL subfractions by unlabeled cellular cholesterol was analyzed in short-term
      experiments. Plasma samples of obese subjects were characterized by a lower
      content of total apolipoprotein A-I (apoA-I) and alpha1-HDL and a lower overall
      capacity to take up labeled cholesterol. In plasma of lean subjects, pre beta2
      HDL and alpha1-HDL appeared to be the most active particles in the initial uptake
      of unlabeled cellular cholesterol. By contrast, in plasmas of obese subjects, the
      pre beta1-HDL appeared to be most active in taking up unlabeled cellular
      cholesterol and transferring [3H]cholesterol. There were negative correlations
      between body mass index (BMI) and apoA-I and alpha1-HDL concentrations, and with
      the apparent increments of cellular cholesterol uptake within pre beta2-HDL and
      alpha1-HDL, as well as with the overall capacity to promote cholesterol efflux.
      By contrast, BMI was positively correlated with the apparent increment in
      cellular cholesterol within pre beta1-HDL. While cholesterol efflux was
      correlated with total plasma apoA-1, there were no such correlations with the
      concentration of any individual HDL subfraction. We conclude that the pattern of
      cholesterol transfer between fibroblasts and high density lipoprotein particles
      is influenced by body fatness and may be a factor in the abnormal metabolism of
      HDL in obesity.

PMID- 9548588
TI  - Interaction of pulmonary surfactant protein A with dipalmitoylphosphatidylcholine
      and cholesterol at the air/water interface.
AB  - Interaction of pulmonary surfactant protein A (SP-A) with pure and binary mixed
      dipalmitoylphosphatidylcholine (DPPC) and cholesterol (3.5 wt%) at the
      air/saline, 1.5 mM CaCl2 interface was investigated using a rhomboid surface
      balance at 37 degrees C. Surface tension-area isotherms were measured to access
      the surface active properties of the monolayers. The organization of DPPC and
      cholesterol in DPPC and DPPC/cholesterol mixed monolayers with or without SP-A at
      equilibrium surface tension (approximately 23 mN/N) was revealed by
      autoradiographs of Langmuir-Blodgett (L-B) films deposited from [14C]DPPC or
      [14C]cholesterol-labeled monolayers. The results showed that SP-A can interact
      with the polar head groups of DPPC monolayers and aggregate DPPC molecules. SP-A
      decreased the surface area reduction required for DPPC monolayers to achieve near
      zero surface tension from 30 to 25% of the area at equilibrium. SP-A also reduced
      the collapse surface tension of pure cholesterol from 27 to 23 mN/m. DPPC and
      cholesterol formed homogeneous mixed monolayers when both were dissolved in the
      spreading solvent prior to spreading, while separate cholesterol-rich domains
      appeared when DPPC and cholesterol were spread successively. Cholesterol resisted
      squeeze-out from either mixed monolayer through compression. Although SP-A could
      not promote the squeeze-out of cholesterol from homogeneous mixed monolayers, it
      facilitated that of cholesterol domains especially when SP-A had first interacted
      with DPPC. These results indicate that pulmonary surfactant protein A facilitates
      the squeeze-out of cholesterol domains from mixed monolayers by condensing DPPC
      and limiting lateral interactions of DPPC with cholesterol domains.

PMID- 9548589
TI  - Identification and characterization of several forms of phospholipase A2 in mouse
      epidermal keratinocytes.
AB  - The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated the
      release of arachidonic acid (AA) from mouse keratinocytes. A distinct difference
      was observed between the fatty acid release profile elicited by TPA and other
      stimuli. These findings led to the investigation of keratinocyte phospholipase A2
      (PLA2), which catalyzes the release of sn-2 fatty acids from membrane
      phospholipids and regulates the production of eicosanoids. We characterized and
      identified several forms of PLA2 in mouse keratinocytes, a cytosolic or cPLA2 and
      two secretory or sPLA2s in the membrane. The PLA2 in keratinocyte cytosol is
      sensitive to heating and acid treatment, while resistant to reducing reagent. The
      PLA2 in keratinocyte membrane is resistant to heating and acid treatment, while
      sensitive to reducing reagent. These characteristics suggested the presence of a
      cPLA2 and at least one type of sPLA2. Inhibitor data further confirmed the
      identities of these PLA2s. The cPLA2 was activated by TPA, and appeared to be
      responsible for the majority of the specific release of AA observed in mouse
      keratinocytes treated with TPA. The calcium ionophore A23187, and 4alpha-TPA did
      not elicit the selectivity towards AA observed with TPA. The release of linoleic
      acid (LA) and oleic acid (OA) from A23187- and 4alpha-TPA-treated keratinocytes
      suggests activation of sPLA2. These activities may be due to the existence of
      both type I and type II sPLA2, as both were identified by polymerase chain
      reactions. In conclusion, keratinocytes express several forms of phospholipase A2
      that differ in their substrate specificities and mechanisms of activation,
      resulting in distinct agonist-specific fatty acid release profiles.

PMID- 9548591
TI  - Quantitation of cholesterol-carrying particles in human gallbladder bile.
AB  - The inter-mixed micellar/vesicular (non-phospholipid-associated) bile salt
      concentration (IMC) can be rapidly measured in model biles by centrifugal
      ultrafiltration, thus allowing reliable separation of vesicular and micellar
      cholesterol carriers by gel filtration with an elution buffer containing bile
      salts at the correct IMC (Donovan, J. M., and A. A. Jackson. 1993. J. Lipid Res.
      34: 1121-1129). We adapted this method to the more complex human gallbladder bile
      and examined the relationship between cholesterol solubilization and
      crystallization in gallbladder biles from 10 cholesterol gallstone patients. The
      IMC (mean +/- SEM) was 9.67 +/- 1.97 (range 3.56-35.02) mM with significant
      enrichment with hydrophilic bile salt species. Upon gel filtration of these biles
      with an eluant buffer containing 10 major bile salts at concentrations according
      to their IMC, cholesterol was found to be solubilized mainly in mixed micelles.
      Vesicles were detected in all 10 biles after separation by KBr density gradient
      ultracentrifugation but in only 5 of these biles with the IMC method. Biles
      without vesicles had a lower CSI (1.15 +/- 0.12 vs. 1.90 +/- 0.28, P < 0.05), a
      higher total lipid concentration (11.9 +/- 2.3 vs. 5.9 +/- 1.1, P < 0.05), and a
      higher bile salt/ (bile salt + phospholipid) ratio (0.83 +/- 0.01 vs. 0.74 +/-
      0.04, P = 0.07). For both IMC and ultracentrifugation methods, vesicular
      cholesterol concentration showed a negative correlation with crystal observation
      time and a positive correlation with cumulative crystal score during 21 days. Our
      data indicate that methods such as density gradient ultracentrifugation
      overestimate vesicular cholesterol solubilization in human biles.

PMID- 9548590
TI  - Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat
      liver during mitochondria and peroxisome proliferation.
AB  - The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic
      acid are mitochondrion and peroxisome proliferators. Administration of these
      promotes an increased transport of endogenous fatty acids to these organelles and
      a higher capacity of beta-oxidation. Administration of 3-thia fatty acids to rats
      resulted in a significant decrease of the hepatic level of docosahexaenoic acid
      (DHA) (17-24%) and especially eicosapentaenoic acid (EPA) (40-80%) accompanied by
      increased gene expression of mitochondrial 2,4-dienoyl-CoA reductase and enoyl
      CoA isomerase. The mitochondrial oxidation of EPA was increased more than 4-fold
      after administration of 3-thia fatty acids. EPA-CoA was a good substrate for
      mitochondrial carnitine acyltransferase-I and treatment with 3-thia fatty acids
      increased the activity 1.7-fold. DHA was a poor substrate for both mitochondrial
      and peroxisomal beta-oxidation. DHA-CoA was a very poor substrate for
      mitochondrial carnitine acyltransferase-I and -II, and the activity did not
      increase after treatment. However, the peroxisomal DHA-CoA oxidase increased 10
      fold after 3-thia fatty acid treatment, whereas the peroxisomal EPA-CoA oxidase
      increased only 5-fold. In isolated hepatocytes, 16% of total metabolized EPA was
      oxidized and 76% was incorporated into glycerolipids, whereas DHA was oxidized
      very little. We conclude that under conditions of increased mitochondrial and
      peroxisomal proliferation by 3-thia fatty acids, a relatively higher oxidation
      rate of polyunsaturated n-3 fatty acids might result in a decreased hepatic level
      of EPA and DHA. Under these conditions DHA seems to be oxidized by the
      peroxisomes, whereas EPA, which can be oxidized in both organelles, is mainly
      oxidized by mitochondria.

PMID- 9548592
TI  - Substrate specificity of retinyl ester hydrolase activity in retinal pigment
      epithelium.
AB  - In the eye, hydrolysis of stored retinyl esters is catalyzed by retinyl ester
      hydrolase (REH) activities in retinal pigment epithelium (RPE) membranes. In the
      present study, biochemical analyses were conducted to determine the substrate
      specificity of these activities. Specific activities determined for hydrolysis of
      various retinol isomers of retinyl palmitate (9-cis-, 11-cis-, 13-cis-, and all
      trans-retinyl palmitates) indicated that 11-cis-retinyl palmitate is
      preferentially hydrolyzed (1.7 nmol/min/mg) compared to the other isomers (0.1
      0.3 nmol/min/mg). Examination of the specificity of REH activity for 11-cis
      retinyl esters of varied acyl chain length (-myristate, -palmitate, and 
      stearate) and degree of saturation (-oleate and -linoleate) further demonstrated
      that palmitate is the preferred fatty acyl moiety. Notably, retinyl esters
      possessing chain lengths which more closely approximate that of the palmitate
      ester exhibited higher rates of hydrolysis. Similar results were obtained in
      retinyl ester-plasma membrane fusion studies in which hydrolysis took place
      within the membrane domain rather than at the lipid-water interface. REH
      substrate specificity was further assessed in competition studies in which 11-cis
      retinyl palmitate hydrolysis was monitored in the presence of 13-cis-, 9-cis-, or
      all-trans-retinyl palmitate. Results show that addition of these retinyl
      palmitate isomers does not affect the rate of hydrolysis of 11-cis-retinyl
      palmitate. However, the hydrolytic rates associated with other retinyl palmitate
      isomers were significantly reduced in the presence of 11-cis-retinyl palmitate.
      Finally, cholesterol ester hydrolase activity was found to be distinct from the
      observed 11-cis-REH activity and the presence of cholesterol oleate did not
      affect the rate of 11-cis-retinyl palmitate hydrolysis. Collectively, these data
      support the hypothesis that a distinct, membrane-associated, 11-cis-retinyl
      palmitate-specific retinyl ester hydrolase activity exists in the retinal pigment
      epithelium.

PMID- 9548593
TI  - Triglyceride-enrichment of high density lipoproteins enhances their remodelling
      by phospholipid transfer protein.
AB  - Phospholipid transfer protein (PLTP) converts high density lipoproteins (HDL) to
      larger and smaller particles during incubation in vitro. The present study shows
      that these conversions are enhanced in triglyceride (TG)-enriched HDL. When pig
      HDL were enriched with TG by incubation with cholesteryl ester transfer protein
      (CETP) and very low density lipoproteins, the TG/apoA-I molar ratio increased
      from 0.7/1 to 11.4/1 and the diameter increased from 9.0 to 9.5 nm. When
      unmodified pig HDL were incubated with PLTP, the diameter increased from 9.0 to
      9.5 nm. Incubation of the TG-enriched pig HDL with PLTP generated larger (13.0
      nm) and smaller (7.5 nm) particles. The composition of the large particles was
      comparable to the non-incubated, TG-enriched HDL. The small particles contained
      only phospholipids and apolipoprotein (apo) A-I. Studies were also carried out
      with spherical, reconstituted HDL (rHDL) containing only cholesteryl esters in
      their core. When the rHDL were enriched with TG by incubation with Intralipid and
      CETP, the diameter increased from 9.0 to 9.2 nm and the TG/apoA-I molar ratio
      became 5.7/1. When unmodified rHDL were incubated with PLTP, the diameter of 15%
      of the particles increased to 11.0 nm, 18% decreased to 7.6 nm, and 67% were
      unchanged. When the TG-enriched rHDL were incubated with PLTP, the diameter of
      62% of the particles increased to 11.4 nm, 26% decreased to 7.6 nm, and 12% did
      not change. Preincubation with Intralipid alone or CETP alone did not enrich the
      rHDL with TG or enhance the size changes. These results show that the TG content
      of HDL has a major influence on PLTP-mediated size changes.

PMID- 9548594
TI  - Modification of a phospholipid stabilized emulsion interface by bile salt: effect
      on pancreatic lipase activity.
AB  - Lipase is activated by binding to an insoluble emulsified or aggregated
      substrate. The extent of binding is related to the physicochemical as well as the
      compositional structure of the interface, the quality of the interface. 'Quality'
      is as yet undefined but thought to contain contributions from electrostatic
      interactions, orientation of substrate, and hydration forces. To investigate the
      electrostatic and compositional factors we have used olive oil-in-water emulsions
      prepared with phosphatidylcholine and four bile salts of varying
      hydrophobicities. By measurement of the droplet zeta potential we have monitored
      semi-quantitatively the incorporation of bile salts within the interface. No
      correlation was found between droplet surface charge as monitored by the zeta
      potential and lag phase. The duration of the observed lag phase was found to be
      inversely related to the degree of incorporation of the bile salts.
      Simultaneously there was evidence of lipase binding to monomeric bile salts,
      reducing its availability for adsorption. Calcium ions reduced the surface charge
      but there was no correlation with lag phase duration. The evidence presented here
      agrees with a more specific role for calcium ions, i.e., the formation of a new
      catalytically active enzyme complex, (enzyme)-(mixed micelle)-(calcium ion).

PMID- 9548595
TI  - Identification of the epitope of a monoclonal antibody that inhibits heparin
      binding of lipoprotein lipase: new evidence for a carboxyl-terminal heparin
      binding domain.
AB  - A panel of 13 monoclonal antibodies to avian lipoprotein lipase (LPL) was
      screened for inhibition of LPL binding to primary avian adipocytes. One
      monoclonal antibody, designated xCAL (monoclonal antibody to chicken adipose
      lipoprotein lipase) 3-6a, was found to inhibit the binding of LPL to primary
      avian adipocytes. In solid phase assays, xCAL 3-6a inhibited the binding of LPL
      to both heparan sulfate and heparin. XCAL 3-6a did not inhibit the catalytic
      activity of the avian enzyme. The monoclonal antibody was not found to cross
      react significantly with bovine lipoprotein lipase. In order to determine the
      location of the epitope of xCAL 3-6a on lipoprotein lipase, several avian
      lipoprotein lipase deletion mutants were constructed and produced as glutathione
      S-transferase (GST) fusion proteins in E. coli. These mutants were screened for
      their ability to react with xCAL 3-6a using Western blotting. The minimum
      continuous fragment of lipoprotein lipase that was required for reactivity
      contained the amino acids 310 to 450. Site-directed mutagenesis of basic residues
      321, 405, 407, 409, 415, and 416 revealed that Arg 405 is necessary for the
      interaction of LPL with xCAL 3-6a. Additional deletions of either the amino- or
      carboxyl-terminal portion of the fragment containing residues 310-450 resulted in
      loss of antibody binding, suggesting that the epitope is a discontinuous one that
      is formed when the termini are brought together through protein folding. Heparin
      Sepharose chromatography of wild-type LPL and a mutant LPL in which the well
      characterized heparin-binding sequence (Arg 281-Lys 282-Arg 284) has been mutated
      was carried out in the presence and absence of xCAL 3-6a. These experiments
      indicate that lipoprotein lipase contains a heparin-binding domain, in addition
      to Arg 281-Arg 284, that can be blocked by xCAL 3-6a.

PMID- 9548596
TI  - 7-Dehydrocholesterol down-regulates cholesterol biosynthesis in cultured Smith
      Lemli-Opitz syndrome skin fibroblasts.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is a common birth defect-mental retardation
      syndrome caused by a defect in the enzyme that reduces 7-dehydrocholesterol to
      cholesterol. Because of this block, patients' plasma cholesterol levels are
      generally low while 7-dehydrocholesterol concentrations are markedly elevated. In
      addition, plasma total sterols are abnormally low and correlate negatively with
      the percent of 7-dehydrocholesterol (r = -0.65, P < 0.0001) suggesting that 7
      dehydrocholesterol might inhibit the activity of HMG-CoA reductase. Cultured skin
      fibroblasts from SLOS patients grown in fetal bovine serum or for 1 day in
      delipidated medium contain little 7-dehydrocholesterol (3 +/- 1% of total
      sterols) and HMG-CoA reductase activities are indistinguishable from that
      measured in control cells. However, raising the 7-dehydrocholesterol
      concentration to 20 +/- 3% of total sterols, equal to the mean proportion in
      plasma of SLOS patients, by either growing cells for 1 week in delipidated medium
      or adding 20 microg/ml 7-dehydrocholesterol directly to the cells reduced HMG-CoA
      reductase activities from 74 +/- 7 to 9 +/- 2 pmol/min per mg protein, or from 92
      +/- 22 to 16 +/- 4 pmol/min per mg protein, respectively (P < 0.01). In contrast,
      adding 20 microg/ml cholesterol evoked a 2- to 4-fold lesser suppression of
      activity (39 +/- 8 pmol/min per mg protein, P < 0.05, vs. 7-dehydrocholesterol).
      HMG-CoA synthase and LDL binding were inhibited equally by 7-dehydrocholesterol
      and cholesterol. Ketaconazole prevented the down-regulation of HMG-CoA reductase
      by 7-dehydrocholesterol, suggesting that an hydroxylated derivative of 7
      dehydrocholesterol may be especially important in suppressing cholesterol
      synthesis. These results demonstrate that 7-dehydrocholesterol, perhaps as an
      hydroxylated derivative(s), is a very effective feedback inhibitor of HMG-CoA
      reductase.

PMID- 9548597
TI  - Apolipoprotein E2 (Arg136 --> Cys) mutation in the receptor binding domain of
      apoE is not associated with dominant type III hyperlipoproteinemia.
AB  - Using apoE phenotyping by immunoblotting and apoE genotyping we identified four
      heterozygous carriers of a rare apolipoprotein (apo) E2 variant, apoE2 (Arg136 -
      > Cys). ApoE2 (Arg136 --> Cys) was not distinct from apoE2 (Arg158 --> Cys) by
      phenotyping, but produced a unique pattern of bands on CfoI restriction typing of
      a 244 bp apoE gene fragment. Two of the four apoE2 (Arg136 --> Cys)/3
      heterozygotes had elevated triglycerides, two were normolipidemic. The
      composition of very low density lipoproteins (VLDL) was normal in each of the
      four apoE2 (Arg136 --> Cys) carriers, regardless of the triglyceride
      concentrations. None of the apoE2 (Arg136 --> Cys) carriers displayed a broad
      beta-band and none revealed beta-migrating particles in the VLDL. The two
      hypertriglyceridemic carriers of apoE2 (Arg136 --> Cys) were, therefore,
      classified as having type IV rather than type III hyperlipoproteinemia. LDL
      receptor binding activities were studied using recombinant apoE loaded to
      dimyristoylphosphatidylcholine (DMPC) vesicles and to VLDL and from an apoE
      deficient individual. LDL receptor binding of apoE2 (Arg136 --> Cys) was 14% of
      apoE3 and was thus higher than that of apoE2 (Arg158 --> Cys). Both apoE2 (Arg136
      --> Cys) and apoE2 (Arg158 --> Cys) displayed substantial heparin binding (61 and
      53% of apoE3, respectively). As the dominant apoE variants known so far are
      characterized by more pronounced reductions of heparin binding, we suggest that
      apoE2 (Arg136 --> Cys) is not associated with dominant expression of type III
      hyperlipoproteinemia. These findings lend support to the concept that apoE
      variants predisposing to dominant type III hyperlipoproteinemia differ from
      recessive mutations by a more severe defect in heparin binding.

PMID- 9548598
TI  - Prebeta-1 HDL in plasma of normolipidemic individuals: influences of plasma
      lipoproteins, age, and gender.
AB  - Prebeta-1 HDL is a molecular species of plasma HDL of approximately 67 kDa mass
      that contains apolipoprotein A-I, phospholipids, and unesterified cholesterol. It
      participates in a cyclic process involved in the retrieval of cholesterol from
      peripheral tissues. In this cycle, unesterified cholesterol from cells is
      incorporated into prebeta-1 HDL, providing a substrate for esterification of
      cholesterol by lecithin:cholesterol acyltransferase. Prebeta-1 HDL then becomes
      incorporated into larger HDL species of alpha mobility as esterification proceeds
      and is regenerated during the transfer of cholesteryl esters from alpha HDL
      particles to acceptor lipoproteins. Thus the steady state level of prebeta-1 HDL
      in plasma reflects the relative efficiencies of the major metabolic processes
      involved in its generation and removal. We have used an isotope dilution
      technique to measure prebeta-1 HDL levels in the plasmas of 136 normolipidemic
      individuals (46 M, 90 F). The mean absolute concentration of prebeta-1 HDL as
      apolipoprotein A-I was 68 +/- 40 microg/ml for women, and 84 +/- 49 m/ml for men.
      Prebeta-1 HDL represented 5.5 +/- 3.3% of total apolipoprotein A-I in women, and
      7.2 +/- 4.0% in men. The distributions of both absolute and percent prebeta-1 HDL
      are highly asymmetric, with skew toward higher values. However, the skew appears
      not to be attributable to either plasma cholesterol or triglyceride levels which
      are also skewed in population samples. The percent prebeta-1 HDL was negatively
      correlated with HDL cholesterol levels (P < 0.0001), whereas absolute levels of
      prebeta-1 HDL were positively correlated with apolipoprotein A-I and negatively
      correlated with HDL cholesterol (P, for both, < 0.0001). Multiple linear
      regression analysis revealed effects of age and gender, but no association with
      lipoprotein fractions other than HDL. Lower levels of prebeta-1 HDL were
      associated with female gender in all models.

PMID- 9548599
TI  - An efficient chromatographic system for lipoprotein fractionation using whole
      plasma.
AB  - We have validated a semi-automatic procedure for the efficient isolation of
      plasma lipoproteins from 300 microl of whole plasma (actual injection volume 200
      microl) by Fast Phase Liquid Chromatography (FPLC). Modified enzymatic assays
      were established to allow the determination of low concentrations (1-20 mg/dl) of
      triglycerides and cholesterol using the Beckman CX-5 Autoanalyzer. The sum of the
      cholesterol contents in the fractions corresponding to low density (LDL) and high
      density lipoprotein (HDL) can be demonstrated to be highly correlated to values
      obtained with dextran sulfate/MgCl2 precipitation for HDLc (slope = 0.98, r2 =
      0.997) and ultracentrifugation (beta-quant) for LDLc (slope = 1.03, r2 = 0.988).
      Using pure lipoprotein fractions isolated by ultracentrifugation, linear ranges
      of detection for HDLc and HDL apoA-I were performed at 18-95 mg/dl and 59-262
      mg/dl, respectively. The ranges for LDLc were 41-435 mg/dl and 21-280 mg/dl for
      LDL apoB. The mean (range) fractional standard deviations for quadruplicate runs
      for 15 individual plasma samples ranging widely in lipoprotein concentrations
      were 0.97 (0.29-2.86%) for LDLc (range: 101.5-258.5 mg/dl), 3.67 (0.62-14.11%)
      for HDLc (range: 27.1-85.1 mg/dl) and 2.19 (0.16-6.56%) for VLDL-TG (range: 6.1
      515.0 mg/dl).

PMID- 9548600
TI  - A 13CO2 breath test to assess the metabolism of triglyceride-rich lipoprotein
      remnants in mice.
AB  - Remnant-like emulsions were prepared with lipid compositions similar to remnants
      derived from triacylglycerol-rich lipoproteins. When injected into the
      bloodstream of conscious mice the remnant-like emulsions labeled with
      cholesteryl[13C]oleate were metabolized in the liver and the appearance of 13CO2
      in the breath was measured. In control mice injected with remnant-like emulsions
      labeled with cholesteryl[13C]oleate, enrichment of 13CO2 in the breath peaked at
      45 min and then decreased markedly by 3 h. In apoE-deficient (-/-) mice no
      enrichment was found and in low density lipoprotein receptor (LDLr)-deficient (-/
      ) mice the appearance of 13CO2 in the breath was markedly decreased. These
      findings were consistent with the ability of the breath test to detect defects in
      remnant metabolism. The breath test was useful in detecting a defect in remnant
      metabolism in LDLr heterozygote (+/-) mice, in which the appearance of 13CO2 in
      the breath was less by 45 min but remained elevated for the duration of the
      experiment when compared with control mice. In hepatic lipase-deficient (-/-)
      mice no defect in remnant metabolism was found. Under fasting conditions, the
      enrichment of 13CO2 in the breath after injection of emulsion was markedly
      increased when compared with fed mice, indicating that the metabolism of the
      injected remnant-like emulsion was probably competed for by post-prandial
      particles under fed conditions. Our findings show that a 13C breath test can be
      used to assess the metabolism of remnants. The test provides a useful and
      sensitive method for non-invasive testing of remnant metabolism in experimental
      animals.

PMID- 9548601
TI  - In vitro concentration response studies and in vitro phase II tests as the
      experimental basis for regional chemotherapeutic protocols.
AB  - The theoretical pharmacologic benefit of regional vs. systemic chemotherapy is
      defined and the concentration response behavior of cytostatic drugs and their
      optimal exposure times are described with human cancer cell lines (HT29,
      NMG64/84) and fresh human tumor cell suspensions in the human tumor colony assay
      (HTCA). The theoretical pharmacological advantages are 5.8 to 6 for adriamycin
      (ADM), 8 for cisplatinum (CDDP), 6.3 for epidoxorubicin (EPI), 22 to 58 for 5
      fluorouracil (5FU), 4.6 for mitomycin C (MMC), and 6.3 for mitoxantrone (NOV).
      The drugs differed in their cytotoxic potency in vitro and thus also potential
      efficacy for regional chemotherapy; however, all but 5-fluorodeoxyuridine (5FUDR)
      exerted cytotoxicity dependent on exposure time and concentration. On average,
      elevation of the test concentrations by 1 lg doubled responses in fresh human
      tumor cell suspensions. From these results and clinical considerations, optimal
      times were defined for the regional chemotherapy strategies of hepatic artery
      infusion, intraperitoneal instillation, and chemoembolisation as performed at our
      institution.

PMID- 9548602
TI  - Isolated limb perfusion in primary and recurrent melanoma: indications and
      results.
AB  - In advanced melanoma of the limbs with in-transit metastasis, melphalan with
      isolated limb perfusion (M-ILP) produces around 50% complete remissions (CR). The
      combination of melphalan with tumour necrosis factor-alpha (TNFalpha) and
      interferon-gamma (IFNgamma) in isolated limb perfusion (TIM-ILP) gives around 80%
      CR. A prospective randomised phase II study compared 32 patients who received TIM
      ILP with 32 patients who received TM-ILP (without IFNgamma). The overall
      remission rate (ORR) and the CR rate were superior with TIM-ILP as compared to TM
      ILP, 100% vs. 91% and 78% vs. 69% respectively, but the differences are not
      significant. Given the efficacy of M-ILP on in-transit metastasis, the procedure
      was tested as an adjunct to surgery in high-risk (Breslow > or = 1.5 mm) primary
      melanoma of the limbs. Through the combined effort of the melanoma groups of the
      European Organization for Research and Treatment of Cancer (EORTC), the World
      Health Organization (WHO), and the North American Perfusion Group, 832 evaluable
      patients from 16 centres were entered in a phase III study. Median followup is
      6.4 years. There was a trend for a longer disease-free interval after M-ILP. The
      difference is significant if the patients without elective lymph node dissection
      (ELND) are separately analysed, with a high significance in the 1.5 to 3 mm
      thickness subgroup. The occurrence of in-transit metastases was reduced from 6.6%
      to 3.3% by M-ILP. There was, however, no benefit of M-ILP in terms of survival.
      Prophylactic M-ILP cannot be recommended as a standard adjunct to surgery in high
      risk primary limb melanoma. TIM-ILP or TM-ILP is a regional therapy with a very
      high regional response rate on melanoma in-transit metastasis.

PMID- 9548603
TI  - Hyperthermic isolated limb perfusion for the treatment of soft tissue sarcomas.
AB  - Hyperthermic isolated limb perfusion (HILP) with various chemotherapeutic agents
      has been used for the local treatment of high-grade soft tissue sarcomas (STS) of
      the extremities, but in most cases, with a disappointing result. Most such
      regimens certainly should not be considered superior to surgery plus
      radiotherapy. Although the majority of extremity STS can be resected locally,
      some are very large and are in close proximity to bone, nerve or blood vessels.
      In these cases, amputation is the only means of resecting the tumour. A new
      combination of drugs used in the set-up of HILP with tumour necrosis factor-alpha
      and melphalan has emerged as a very promising option for the limb-saving
      management of locally advanced STS. In recent studies, complete response rates of
      approximately 30% and partial remission rates of 50% have been achieved, while
      the overall limb-salvage rate is more than 80%.

PMID- 9548605
TI  - Toxicity and morbidity of isolated limb perfusion.
AB  - Because a relationship between toxicity and treatment outcome has never been
      demonstrated for isolated limb perfusion (ILP) with melphalan, it is important to
      keep the side-effects of the procedure restricted to a minimum. Risk factors for
      more severe acute regional toxicity have recently been identified with tissue
      temperature above 40 degrees C and a high melphalan peak concentration being the
      most important. Acute regional toxicity should be mild taking into account these
      factors and maintaining the normal physiological conditions in the limb during
      ILP. This should also decrease the incidence of long-term morbidity, especially
      ankle stiffness and muscle atrophy, since a relation between the severity of the
      acute regional tissue reactions and long-term morbidity has been demonstrated.
      Lymphedema is strongly linked to a concomitant regional lymph node dissection and
      this operation may be delayed until the acute regional tissue reactions have
      faded. It is not yet clear whether the addition of tumor necrosis factor-alpha
      (TNF-alpha) to melphalan increases regional toxicity. In the absence of melphalan
      leakage to the systemic circulation, systemic toxicity is minimal; this is also
      true with TNF-alpha. Compared to ILP with melphalan +/- TNF-alpha, ILP with other
      drugs is less effective and often is associated with increased regional toxicity.

PMID- 9548604
TI  - The application of hyperthermia in regional chemotherapy.
AB  - To evaluate the role of hyperthermia combined with chemotherapy in the loco
      regional treatment of tumors, a retrospective analysis was done with 228 limb
      melanoma patients treated with hyperthermic antiblastic perfusion (HAP). A series
      of treatment- and tumor-related prognostic factors was analyzed to establish
      their influence on tumor response, loco-regional control, and survival.
      Concerning tumor response, the logistic model showed that the number of lesions
      and the minimal tumor temperature (min T) maintained their individual predictive
      values (P < 0.000001 and P = 0.04, respectively). For loco-regional control, only
      the number of lesions had a significant predictive value. No direct correlation
      was found between the treatment-related variables and loco-regional control.
      However, the 5-year survival rate was significantly higher for patients who
      achieved a complete response (CR) (51.5%, P = 0.0033) as compared to those who
      did not (33.3%), providing indirect evidence of the role of the treatment.
      Multivariate analysis showed that both disease-free and overall survival are
      strongly influenced by numerous clinical variables and the min T always
      maintained its significance. When analyzing the subgroup of 119 patients
      evaluable for tumor response, the Cox model selected the tumor response as the
      dominant factor for both disease-free and overall survival. These data seem to
      demonstrate that the optimization of treatment parameters is crucial in
      determining the CR rate, which, in turn, positively affects the disease outcome.
      HAP is the treatment of choice for recurrent limb melanoma, and hyperthermia
      plays an important role in exploiting the efficacy of this technique.

PMID- 9548606
TI  - Tumor necrosis factor-alpha in isolated perfusion systems in the treatment of
      cancer: the Rotterdam preclinical-clinical program.
AB  - The clinical success of the application of tumor necrosis factor-alpha (TNFalpha)
      in isolated limb perfusions in patients with advanced sarcomas, melanomas and
      other tumors has renewed the interest in this agent as an anticancer drug. At the
      Rotterdam Cancer Center, we have developed an interactive preclinical-clinical
      TNFalpha program that explores new methods to use TNFalpha in various settings.
      Regional organ perfusion models were developed and the effectivity of targeting
      of TNFalpha to the tumor by means of systemic administration of liposomes are
      tested. Furthermore various drugs and mechanisms that may enhance the activity of
      TNFalpha are under investigation. A summary of this comprehensive program is
      presented here.

PMID- 9548607
TI  - Isolated limb infusion with cytotoxic agents: a simple alternative to isolated
      limb perfusion.
AB  - Isolated limb perfusion (ILP) with cytotoxic agents is an effective but complex
      procedure. Isolated limb infusion (ILI) has been developed as a simpler
      alternative. Catheters are inserted percutaneously into the axial artery and vein
      of the affected limb and a pneumatic tourniquet is inflated proximally. Cytotoxic
      agents are then infused through the arterial catheter and circulated with a
      syringe for 15 to 20 minutes. Progressive hypoxia occurs, but normothermia is
      maintained. To date, 175 ILIs have been performed: 164 for melanoma and 11 for
      other tumours. Results obtained are similar to those obtained by conventional
      ILP. Morbidity is low and treatment of frail and elderly patients who would not
      tolerate ILP is possible. An elective double ILI protocol can be used to obtain
      the additional benefits of fractionated chemotherapy. The possibility of
      increasing ILI response rates by using other drugs and drug combinations and by
      multiple fractionated dosing is being investigated.

PMID- 9548608
TI  - Intra-arterial infusion: overview and novel approaches.
AB  - Intra-arterial infusion includes a variety of treatment modalities, adjusted
      selectively to chemosensitivity and vascularization. For most drugs, response
      behaviour of different tumors is concentration dependent and requires improved
      modes of application of cytotoxics. In the treatment of liver metastases from
      colorectal cancer and hepatocellular carcinoma, blood flow reduction by micro
      embolization with starch microspheres has brought significant advantage in
      response. Balloon stopflow infusion combined with micro-embolization induced 83%
      complete remissions in a study including 100 patients with locally recurrent
      breast cancer. Stepwise increased local exposure demonstrated concentration
      dependent response. Stopflow infusion of the celiac axis combined with
      microspheres for advanced Stage III and IV pancreatic cancer induced a 96%
      remission rate (n = 24 patients) at a median survival of 10 months. This was
      confirmed in a series of consecutive studies including 242 patients. Quality of
      life was significantly improved in all responding patients. Overall pain response
      was 80%. A prospective randomized trial in this patient group, comparing systemic
      vs. regional chemotherapy in the form of intra-arterial infusion with tumor
      adjusted concentrations, was stopped in an early phase because median survival
      time was significantly prolonged (P = 0.001) in the arterial group.

PMID- 9548609
TI  - Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and
      treatment of peritoneal carcinomatosis and sarcomatosis.
AB  - Intraperitoneal chemotherapy and cytoreductive surgery have been combined to
      reach treatment objectives in patients with peritoneal carcinomatosis or
      sarcomatosis that neither modality by itself can achieve. These treatments must
      be combined with the proper selection of patients in order to observe "high
      value" results from therapy. There are three principles of management to support
      treatments for peritoneal carcinomatosis and sarcomatosis. First, the clinician
      must select patients who have isolated disease distributed on the surfaces of
      abdominal and pelvic structures. Patients treated for peritoneal implants who
      have persistent disease at other sites will profit little or not at all. Second,
      this disease must be reduced to its lowest possible mass by peritonectomy
      procedures and resections of viscera. Third, maximal intraperitoneal and systemic
      chemotherapy are utilized to eradicate the disease on peritoneal surfaces as well
      as control the primary or recurrent tumor. These principles of management and a
      presentation of the results achieved to date are reviewed.

PMID- 9548611
TI  - The Internet--friend or foe to scientific journals?

PMID- 9548610
TI  - Delivery of anticancer drugs via isolated hepatic perfusion: a promising strategy
      in the treatment of irresectable liver metastases?
AB  - The prognosis of patients with irresectable liver metastases derived from
      colorectal cancer is invariably poor; unfortunately, these tumours show only
      minor responses to conventional anticancer agents. The best responses have been
      obtained by fluoropyrimidines delivered as continuous infusion into the hepatic
      artery (HAI): their rapid uptake and detoxification by liver cells results in
      relatively low systemic drugs levels. This approach increases mean survival
      duration from 17 to 26 months and, in few patients, causes "down-staging" that
      may result in resectability. To improve opportunities for chemotherapy, the
      technique of 1-hour recirculating perfusion of the vascularly isolated liver
      (isolated hepatic perfusion, IHP) was developed. If leakage to the systemic
      circulation is negligible-and the compounds used do not readily cause
      hepatotoxicity-IHP allows usage of drug doses that would be fatal if delivered
      systemically. Because alkylating agents generally have steep dose-response
      curves, mitomycin C (MMC) and melphalan (L-PAM) entered phase I/II studies on
      IHP. Using these drugs, IHP was performed in principle as a single procedure in
      60 otherwise untreated patients at our institution. However, despite preliminary
      data that indicate impressive clinical responses are obtained, improvement over
      HAI will probably be minor. Because IHP is a complicated way of drug delivery,
      one could argue that its use is justified only when it has the potential to kill
      all tumour cells in the liver. We critically discuss the possibilities of IHP
      and/or the use of gene therapy in an IHP setting.

PMID- 9548612
TI  - The introduction of H2-receptor antagonists to Scandinavia: effects of experts'
      opinions.

PMID- 9548613
TI  - Lansoprazole, amoxicillin, and clarithromycin triple therapy in vagotomized
      patients with dyspeptic complaints. A randomized, double-blind, placebo
      controlled, clinical study without pretreatment diagnostic upper endoscopy.
AB  - BACKGROUND: The Maastricht Consensus Report advises that, in Helicobacter pylori
      positive patients after surgery for peptic ulcer disease, H. pylori should be
      eradicated. The aim of the present study was to investigate the symptomatic
      response of H. pylori eradication in previously vagotomized peptic ulcer patients
      with persistent dyspeptic complaints. METHODS: The study was performed as a
      randomized, double-blind, placebo-controlled study. Pretreatment diagnostic upper
      endoscopy was omitted. All the results were submitted to intention-to-treat and
      efficacy analyses. RESULTS: We could not find any differences between the two
      groups with regard to intensity or frequency of upper abdominal pain, nausea,
      heartburn, or other abdominal symptoms during the 12-month follow-up. The triple
      therapy eradication rate was 88% at both 3- and 12-month controls. CONCLUSION:
      Vagotomized peptic ulcer patients with persistent dyspeptic complaints should
      undergo a diagnostic upper endoscopy to detect ulcer recurrence before H. pylori
      eradication treatment is considered.

PMID- 9548614
TI  - Gastric meal accommodation studied by ultrasound in diabetes. Relation to vagal
      tone.
AB  - BACKGROUND: Disturbed gastric meal accommodation may cause abdominal symptoms in
      patients with functional dyspepsia and diabetes mellitus who have poor vagal
      control of gastric motility. In the present study we aimed to explore the
      relation between gastric meal accommodation and vagal tone in diabetic patients
      with vagal neuropathy. METHODS: Twenty patients with diabetes (DM) (insulin
      dependent type; 10 men and 10 women, aged 35.3 +/- 7.6 years) and 20 healthy
      controls (HC) (10 men and 10 women; aged 34.7 +/- 10.7 years) were studied.
      Proximal gastric size was assessed with ultrasound in a sagittal area and a
      frontal diameter. Distal gastric (antrum) size was assessed in a sagittal area.
      Vagal tone was assessed non-invasively by recording of respiratory sinus
      arrhythmia (RSA) in beats per minute. RESULTS: Proximal sagittal area was
      significantly (P = 0.03) smaller in DM (18.5 +/- 5.5 cm2) than in HC (22.2 +/-
      4.6 cm2). Proximal frontal diameter did not differ significantly (P = 0.60)
      between DM and HC (5.9 +/- 1.1 cm versus 5.7 +/- 0.8 cm). Antral area, too, did
      not differ significantly (P = 0.59) between DM and HC (14.5 +/- 4.1 cm2 versus
      13.6 +/- 5.8 cm2). Proximal/distal meal distribution ratio, defined as proximal
      sagittal area/distal sagittal area, was significantly (P = 0.05) smaller in DM
      (6.8 +/- 0.6) than in HC (9.9 +/- 5.5). Vagal tone was significantly (P = 0.03)
      lower in DM (4.5 +/- 1.9 beats/min) than in HC (6.3 +/- 2.7 beats/min). Vagal
      tone tended (r = 0.33, P = 0.06) to correlate with proximal sagittal area in DM
      and HC pooled. Vagal tone correlated (r = 0.34, P = 0.05) with proximal frontal
      diameter in DM and HC pooled. A significant negative correlation (r = -0.39, P =
      0.03) was observed between vagal tone and antral area in DM and HC pooled.
      CONCLUSIONS: Patients with diabetes and low vagal tone have an impaired
      postprandial gastric meal distribution characterized by a small proximal stomach
      and a small proximal/distal meal distribution ratio.

PMID- 9548615
TI  - The ability of enteric diarrhoeal pathogens to ferment starch to short-chain
      fatty acids in vitro.
AB  - BACKGROUND: Short-chain fatty acids (SCFA), produced in the normal colon by
      bacterial fermentation, are decreased in acute diarrhoea. This may have
      deleterious effects on epithelial function in the colon. METHODS: The ability of
      several diarrhoeal pathogens to produce SCFA when incubated with starch in vitro
      was studied. Isolated pathogens were incubated for 24 h with either no added
      substrate, glucose, or starch under anaerobic conditions, and SCFA were
      quantitated by gas-liquid chromatography. RESULTS: Unlike the normal colonic
      flora, the pathogens produced acetate but not propionate or butyrate. D-Lactate
      was also produced by all the pathogens studied. When the pathogens were incubated
      in anaerobic medium containing starch, significantly greater amounts of acetate
      and significantly lesser amounts of lactate were produced. CONCLUSIONS: The
      inability of enteric pathogens to produce butyrate may impair epithelial cell
      function, whereas production of D-lactate may enhance mucosal damage in
      diarrhoeal disease. The presence of luminal starch may be helpful in shifting the
      fermentation profile to a more favourable pattern.

PMID- 9548616
TI  - Depressive symptoms in adult coeliac disease.
AB  - BACKGROUND: Psychic symptoms and depression have been reported in coeliac disease
      (CD). The aim of this study was to explore depression in a large cohort of adult
      CD patients. METHODS: Depressive symptoms were evaluated in 92 adult coeliacs,
      100 normal controls (NC), and 48 chronic persistent hepatitis (CPH) patients by
      means of a modified version of the Zung Self-Rating Depression Scale (M-SDS). CD
      patients were evaluated for the level of knowledge about CD and the compliance
      with diet. RESULTS: The M-SDS score differentiated CD patients from NC. Age at
      diagnosis and duration of and compliance with diet did not correlate with
      depression. Three main factors could be identified with the M-SDS:
      'reactiveness', 'pessimism', and 'anhedonic-asthenic'. CONCLUSION: Depressive
      symptoms are a feature of CD; they are present to a similar extent in patients
      with childhood- and adulthood-diagnosed CD. The results underline the relevance
      of personal psychologic resources, which play a fundamental role in determining
      and sustaining depression.

PMID- 9548617
TI  - IgA- and IgG-class antihuman umbilical cord antibody tests in adult coeliac
      disease.
AB  - BACKGROUND: An antiendomysium antibody test using human umbilical cord as antigen
      has recently been introduced. METHODS: We determined IgA- and IgG-class antihuman
      umbilical cord (HUC-ab), antireticulin (ARA), and antigliadin antibodies (AGA) in
      92 untreated adult coeliac patients, in 95 non-coeliac subjects, and in 4 coeliac
      patients with selective IgA deficiency. Tissue antibodies were measured with an
      indirect immunofluorescence method and AGA with an enzyme-linked immunosorbent
      assay. RESULTS: Of adult coeliac patients 85% were positive for IgA-class HUC-ab,
      78% were positive for ARA, and 80% for AGA; the specificity for HUC-ab and ARA
      was 100%, and for AGA 86%. Combination of HUC-ab, ARA, and high-titre AGA
      increased the sensitivity to 96% without loss of specificity. IgG-class HUC-ab
      was positive in 12% of coeliac patients, in all four coeliac patients with IgA
      deficiency, and in none of the controls. CONCLUSIONS: The HUC-ab test is highly
      specific but not 100% sensitive for detecting adult coeliac disease. A
      combination of the IgA-class HUC-ab, ARA, and high-titre AGA tests is
      recommended. In selective IgA deficiency the IgG-class HUC-ab test seems to work
      well.

PMID- 9548618
TI  - Fecal alpha-1-antitrypsin excretion in children with diarrhea.
AB  - BACKGROUND: The aim of this study was to compare the concentration and
      immunoelectrophoretic characterization of alpha-1-antitrypsin (AAT) excreted in
      random fecal samples in children with acute and chronic diarrhea and in control
      groups. METHODS: Thirty-two children with diarrhea and 23 healthy children were
      evaluated. The concentration and characterization of AAT were determined by
      radial immunodiffusion and crossed immunoelectrophoresis, respectively. RESULTS:
      The increase in the concentration of fecal AAT was more than the upper limit for
      the control group (1.25 mg/g of dry stool mass) in the patients with chronic
      infectious diarrhea and in 52% of those with chronic non-infectious diarrhea but
      not in those with acute diarrhea, infectious or non-infectious.
      Immunoelectrophoretic analysis showed two forms of fecal AAT in both sick and
      healthy children. The alterations in the concentration of fecal AAT did not
      correlate with the immunoelectrophoretic pattern of AAT. CONCLUSION: Our results
      suggest that the determination of fecal AAT could give clinically useful
      information about the difference between infectious and non-infectious diarrhea
      and the activity of characterizing disease with diarrhea.

PMID- 9548619
TI  - Time trends for peptic ulcer disease in Denmark, 1981-1993. Analysis of
      hospitalization register and mortality data.
AB  - BACKGROUND: Since the mid-1980s there has been great improvement in the available
      diagnostic tools and treatments for peptic ulcers. The aim of this study was to
      determine whether these improvements have been paralleled by decreasing age- and
      sex-specific hospitalization and death rates for peptic ulcers in Denmark.
      METHODS: The study was based on all discharges from Danish somatic hospitals as
      registered in the National Hospital Discharge Registry and all the death
      certificates as registered in the Danish National Board of Health from 1981
      through 1993, when a diagnosis of peptic ulcer was recorded. The age- and sex
      specific and age-adjusted hospitalization and death rates were estimated.
      RESULTS: In men the age-adjusted hospitalization rate for all types of peptic
      ulcers decreased by 0.88, but the mortality increased by 1.19. In women the age
      adjusted hospitalization and mortality increased for all types of peptic ulcers.
      The increasing mortality was mainly due to bleeding and perforated duodenal
      ulcers. The analysis of the age-specific hospitalization and mortality for peptic
      ulcer complications showed that the increasing trends mainly occurred among the
      elderly. CONCLUSION: The improved medical treatment of peptic ulcers has not been
      paralleled by decreasing hospitalization or death from complicated peptic ulcers
      in Denmark. On the contrary, we found an increasing hospitalization and mortality
      from peptic ulcer complications, particularly in elderly Danish people.

PMID- 9548620
TI  - The influence of Helicobacter pylori eradication on the gastric mucosal content
      of epidermal growth factor, transforming growth factor-alpha, and their common
      receptor.
AB  - BACKGROUND: The relationship between the expression of epidermal growth factor
      (EGF) and transforming growth factor-alpha (TGF-alpha) and that of their receptor
      (EGF-R) in the Helicobacter pylori-infected gastric mucosa has not been
      completely elucidated. The aim of this study was to examine the interplay between
      H. pylori colonization and gastric mucosal growth factor content. METHODS: By
      means of a solid-phase enzyme-linked immunosorbent assay EGF, TGF-alpha, and EGF
      R levels and interleukin-1beta (IL-1beta) content, which is considered a marker
      of chronic inflammation, were evaluated in the antral mucosa of 24 H. pylori
      positive patients before and 8 weeks after eradication therapy. RESULTS: After
      therapy H. pylori was eradicated in 19 patients. The eradication was accompanied
      by a significant decrease in IL-1beta content and an increase in EGF and TGF
      alpha levels. On the other hand, in the five patients in whom the bacterium was
      not eradicated EGF, TGF-alpha, and EGF-R levels were quite similar to those
      assayed before therapy, whereas IL-1beta content was still high. CONCLUSIONS:
      These results suggest that H. pylori exerts an inhibitory effect on the mucosal
      expression of EGF and TGF-alpha, which are likely involved in the gastric mucosa
      repair process.

PMID- 9548621
TI  - Antigastric autoantibodies and gastric secretory function in Helicobacter pylori
      infected patients with duodenal ulcer and non-ulcer dyspepsia.
AB  - BACKGROUND: Autoantibodies against epitopes located at the canaliculi of human
      parietal cells occur in about 30% of Helicobacter pylori-infected patients. This
      has led to the hypothesis that gastric secretory function could be inhibited by
      anticanalicular autoantibodies in H. pylori gastritis. METHODS: Forty-four H.
      pylori-infected patients with and without duodenal ulcers were screened for
      anticanalicular autoantibodies by means of immunohistochemistry. Plasma gastrin
      levels and basal and maximal gastric acid output were determined. RESULTS:
      Fasting gastrin levels were significantly increased in the group with
      anticanalicular autoantibodies. In the group of patients with non-ulcer dyspepsia
      the presence of anticanalicular autoantibodies was significantly correlated with
      an impaired basal acid secretion. CONCLUSIONS: Antigastric autoimmunity in H.
      pylori gastritis seems to be relevant for gastric hyposecretion either directly
      by inhibiting the proton pump or indirectly through the development of gastric
      mucosa atrophy.

PMID- 9548622
TI  - Evaluation and validation of a Crohn's disease inflammatory activity index
      reflecting pattern of endoscopic severity.
AB  - BACKGROUND: This study was designed to investigate objective variables assessing
      the inflammatory activity of Crohn's disease accessible for routine management
      and their suitability to act as surrogate indicators for endoscopic alterations.
      METHODS: Thirty-six patients were included in a prospective study and underwent
      endoscopic investigation, 18 with clinically exacerbated disease and 18 after
      acute-phase conservative therapy. The endoscopic findings were classified to
      define the dependent variable, yielding two categoric levels: acute active
      disease and remission. The extent of affected mucosal area was not taken into
      consideration. The serum variables alpha1-antitrypsin, acid alpha1-glycoprotein
      (AGP), C-reactive protein (CRP), sialic acids, prealbumin (PAB), and albumin were
      used as independent variables to predict the dependent variable. To compare the
      results with common indices, the Crohn's Disease Activity Index (CDAI) and van
      Hees Index were calculated. RESULTS: The following model was calculated by
      stepwise logistic regression analysis: if AGP (mg/dl) -4.2 x PAB (mg/dl) > or
      =0.8, then endoscopically active disease will be predicted with a sensitivity of
      100% and a specificity of 95% (P < 0.001). The predictive values of the single
      variables, CDAI, and van Hees Index were lower. For validation of results an
      analogous study was performed including 44 patients, 29 with active disease and
      15 controls. The existence of the model was confirmed, again showing high values
      for sensitivity (86%) and specificity (100%). CONCLUSIONS: On a qualitative level
      focusing on clinical relevance, the endoscopic and biologic findings of Crohn's
      disease are highly associated. In addition to clinical assessment, usage of the
      developed index as a rationale contributing to therapeutic decisions in the short
      and long-term management might be reasonable.

PMID- 9548623
TI  - Chronic inflammatory changes in the pouch mucosa are associated with cholangitis
      found on peroperative liver biopsy specimens at restorative proctocolectomy for
      ulcerative colitis.
AB  - BACKGROUND: The clinical syndrome of primary sclerosing cholangitis (PSC),
      diagnosed in about 5% of patients with ulcerative colitis (UC), has been shown to
      be associated with pouchitis after ileal pouch-anal anastomosis. The aim of this
      study was to ascertain whether UC patients with cholangitis on liver biopsy at
      proctocolectomy, with or without the clinical syndrome of PSC, have an increased
      risk of inflammatory changes in the ileal reservoir mucosa and clinical
      pouchitis. METHODS: Of the consecutive 81 UC patients treated with restorative
      proctocolectomy with ileal J reservoir at Tampere University Hospital between
      1985 and 1991, 73 with peroperative liver biopsy were included. A peroperative
      liver biopsy was obtained during proctocolectomy. After a median follow up of 64
      months, pouch biopsy specimens were obtained. Periods of clinical pouchitis were
      diagnosed by means of clinical criteria alone or by clinical criteria combined
      with the results of previous pouch endoscopies in all patients. RESULTS: Ten
      patients (14%) showed histologic features consistent with small-duct PSC on liver
      biopsy. Endoscopic retrograde cholangiography had previously been performed on
      four of these patients, and all four had large-duct PSC. Patients with
      cholangitis had significantly more severe chronic, but not acute, inflammation in
      the pouch mucosa than patients without cholangitis. At least one episode of
      pouchitis occurred in 30% of the patients without cholangitis as compared with
      90% of the patients with cholangitis. Chronic pouchitis was more frequent in the
      group with cholangitis than in the group without it (70% versus 11%).
      CONCLUSIONS: The only means of detecting all UC patients with cholangitis is a
      liver biopsy. Cholangitis, either with the clinical syndrome of PSC or found on
      liver biopsy, seems to be a risk factor for chronic-type inflammatory changes in
      the pouch mucosa and for the development of pouchitis.

PMID- 9548625
TI  - Expression of CD44 and variant proteins in human colorectal cancer and its
      relevance for prognosis.
AB  - BACKGROUND: CD44 is a cell adhesion molecule often expressed in the form of
      various splice variants. The role of standard CD44 isoform (CD44s) and its
      variants in colorectal carcinogenesis is partly conflicting. Therefore, we
      compared the expression of CD44s (hermes-3) and its splice variants (v3 and v6)
      with traditional prognostic factors in 194 colorectal cancer patients treated at
      Kuopio University Hospital and followed up for a mean of 14 years. METHODS:
      Formalin-fixed, paraffin-embedded tissue sections from 194 patients with
      colorectal carcinoma were examined immunohistochemically to detect the expression
      of different forms of CD44. The hypothesis that CD44s, CD44v3, and CD44v6
      expression intensities and distribution in cancer cells correlated with survival
      was tested with the log-rank test, hazard ratios, and their confidence intervals.
      RESULTS: In high-grade tumours CD44s and CD44v6 expression intensities and CD44s
      percentages were stronger than in low-grade tumours. CD44v6, CD44v3, and CD44s
      expression intensities in tumour epithelium were also stronger in Dukes C and D
      tumours than in A and B tumours. In the univariate survival analysis patients
      with strong CD44s, CD44v3, and CD44v6 expression intensities in tumour epithelium
      had lower cancer-related survival than the patients who had weak CD44s, CD44v3,
      and CD44v6 expression intensities. Recurrence-free survival was also shorter in
      patients with intense signals for CD44v3 and CD44v6 in tumour epithelium. In the
      multivariate analysis the CD44v6 expression intensity in tumour epithelium
      predicted independently both cancer-related and recurrence-free survival in T1
      4N0-3M0 and T1-3N0M0 cases. In addition, the CD44v3 expression intensity in
      tumour epithelium was a significant predictor of RFS in T1-3N0M0 cases.
      CONCLUSIONS: These results strongly suggest that the CD44 splice variants v6 and
      v3 have prognostic significance in colorectal cancer.

PMID- 9548624
TI  - Gastric cancer and premalignant lesions in atrophic gastritis: a controlled trial
      on the effect of supplementation with alpha-tocopherol and beta-carotene. The
      Helsinki Gastritis Study Group.
AB  - BACKGROUND: Vitamin E and beta-carotene are considered to decrease the risk of
      gastric cancer both in humans and in laboratory animals. We studied the effect of
      dietary supplementation with alpha-tocopherol and beta-carotene on the end-of
      trial prevalence of premalignant and malignant lesions of the stomach in older
      men with atrophic gastritis. METHODS: The study was carried out within the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in
      which 29,133 male smokers aged 50-69 years were randomly assigned to receive
      daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or
      placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3
      years' supplementation to find men with atrophic gastritis. A low serum
      pepsinogen I level, indicating atrophic gastritis of the corpus area of the
      stomach, was found in 2132 men. These men were invited to have upper
      gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects
      after a median supplementation time of 5.1 years. RESULTS: Neoplastic alterations
      were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade
      (moderate dysplasia), 7 with definite dysplasias of high grade (severe
      dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with
      carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence
      interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence
      interval, 0.65-1.95) supplementation had any association with end-of-trial
      prevalence of gastric neoplasias after adjustment for other possible risk
      factors. The effect was not modified by base-line serum level or dietary intake
      of vitamins, prevalence of Helicobacter pylori infection, or other covariates.
      CONCLUSIONS: We thus conclude that supplementation with alpha-tocopherol or beta
      carotene for 5 years has no major impact on the occurrence of neoplastic changes
      of the stomach in older male smokers with atrophic gastritis.

PMID- 9548626
TI  - Benzodiazepine-like compounds in the plasma of patients with fulminant hepatic
      failure.
AB  - BACKGROUND: Benzodiazepine-like compounds have been implicated in the
      pathogenesis of encephalopathy after fulminant hepatic failure. METHODS: The
      levels and the nature of benzodiazepine-like compounds were determined in six
      cases of fulminant hepatic failure during the course of the disease. Blood
      samples were collected on admission and a few days later, when the neurologic
      status had improved in five cases and immediately before death in one case. The
      compounds were measured in sera with a binding technique after high-performance
      liquid chromatography purification and analyzed with mass spectrometry. RESULTS:
      Their levels were highly variable in those with severe encephalopathy and were
      still increased on awakening in some cases. Diazepam and N-desmethyldiazepam were
      inconsistently present. CONCLUSIONS: The inconsistent presence of benzodiazepine
      like compounds in encephalopathy after fulminant hepatic failure and their
      persistence, in some cases, at high levels on awakening from coma seem to
      indicate that the encephalopathy is not strictly dependent on the levels of these
      compounds.

PMID- 9548627
TI  - Time course-dependent evolution of nitric oxide-mediated arterial hyporeactivity
      to phenylephrine in rats with ligated bile duct.
AB  - BACKGROUND: Nitric oxide (NO) may be heavily involved the phenomenon of arterial
      vasodilation in cirrhosis. However, the subject is still controversial. AIM: This
      study therefore characterizes the dynamic role of the NO system during
      development of experimental cirrhosis. METHODS: The contractile response to
      phenylephrine of thoracic rat aortic rings was studied in vitro before and after
      nitric oxide blockade. Experiments were performed 1, 2, 3, and 4 weeks after
      induction of cirrhosis via bile duct ligation with an appropriate control group.
      RESULTS: In bile duct-ligated rats reduction of the maximum contractile response
      to phenylephrine was 4.4 +/- 7.3% after 1 week, 22.7 +/- 8.7% after 2 weeks, 48.4
      +/- 8.3% after 3 weeks, and 64.6 +/- 8.9% after 4 weeks, in comparison with the
      control group. This reduction in contractility to phenylephrine was completely
      reversed by blocking NO synthesis. CONCLUSION: The data presented indicate a
      dynamic decrease in contractile response to phenylephrine even at an early stage
      of secondary cirrhosis. Reversibility of the effect after NO synthesis blockade
      suggests that increased NO synthesis is a major factor in vascular hyporeactivity
      to vasoconstrictors in cirrhosis.

PMID- 9548628
TI  - Increased plasma, biliary, and hepatic cholesterol precursors in pigs with ileal
      autotransplantation-induced malabsorption of cholesterol and bile acids.
AB  - BACKGROUND: Small-bowel transplantation impairs intestinal absorptive function
      for unknown reasons. METHODS: The proportions of plasma, biliary, and hepatic
      cholesterol precursors to cholesterol were determined by gas-liquid
      chromatography after resection of the proximal 75% of the porcine jejunoileum (n
      = 15) and autotransplantation of the remaining ileum (n = 15) and were related to
      in vivo absorption and fecal excretion of cholesterol. RESULTS: Ileal
      autotransplantation significantly decreased serum (18%; P < 0.05) and liver
      (7.6%; P < 0.05) cholesterol content, the esterification percentage of serum
      cholesterol (5.1%; P < 0.0001), and the total amount of cholesterol absorbed
      (48%; P < 0.05) and increased fecal excretion of bile acids (108%; P < 0.0001),
      net cholesterol elimination (53%; P < 0.001), and the proportions of plasma
      (207%; P < 0.0001), biliary (183%; P < 0.0001), and hepatic (114%; P < 0.0001)
      cholesterol precursors. The increases were most striking for the side-chain
      saturated demethylated sterols, cholesterol and lathosterol, and monomethyl
      sterols, whose bile/liver and plasma/liver ratios were increased in the
      autotransplantation group. Plasma, biliary, and hepatic precursor proportions
      were positively related to each other and similarly correlated with fecal bile
      acids and the net elimination of cholesterol in feces. CONCLUSIONS: These
      findings suggest that ileal autotransplantation in pigs with proximal gut
      resection increased the levels of cholesterol precursor sterols in plasma, bile,
      and liver mainly due to a bile-acid-malabsorption-induced increase in hepatic
      synthesis of cholesterol. Enhanced secretion of cholesterol precursors from the
      liver into the plasma and bile may have contributed to their increased values
      during the increased rate of cholesterogenesis.

PMID- 9548629
TI  - Comparative clinical evaluation of the 13C-mixed triglyceride breath test as an
      indirect pancreatic function test.
AB  - BACKGROUND: Breath tests using stable isotopes of carbon or hydrogen are
      increasingly becoming established for the evaluation of various gastrointestinal
      functions, including measurement of exocrine pancreatic insufficiency. We wanted
      to evaluate the clinical relevance of the non-invasive, non-radioactive 13C-mixed
      triglyceride breath test in comparison with the secretin-caerulein test as the
      'gold standard' of pancreatic function testing and with faecal chymotrypsin and
      elastase 1 in patients with mild and severe exocrine pancreatic insufficiency.
      METHODS: The secretin-caerulein test, faecal fat analysis, 13C-mixed triglyceride
      breath test, faecal elastase 1, and chymotrypsin and various morphologic
      investigations were done in 26 patients with mild (n = 13) or severe (n = 13)
      exocrine pancreatic insufficiency and 25 patients with gastrointestinal diseases
      of non-pancreatic origin. Twenty-seven healthy volunteers served as normal
      controls. After a 12-h fast 200 mg mixed triglyceride (1,3-distearyl,2(carboxyl
      13C)octanoyl glycerol) were orally administered with a test meal, and breath
      samples were taken before and at 30-min intervals for 5 h thereafter, and the
      increase in 13C/12C isotopic ratio in breath was analysed by mass spectrometry.
      Various modifications of the test procedure were investigated. RESULTS:
      Specificity for impaired pancreatic function was higher for faecal elastase (90%)
      and equal for faecal chymotrypsin (82%) as compared with the various variables of
      the 13C-mixed triglyceride breath test (69-85%). The sensitivity of the 13C-mixed
      triglyceride breath test for total and separately for mild and severe exocrine
      pancreatic insufficiency was higher (total, 69-81%) than that of faecal
      chymotrypsin (total, 56%) but lower than faecal elastase (total, 92%).
      CONCLUSION: The 13C-mixed triglyceride breath test very sensitively reflects
      severe exocrine pancreatic insufficiency (steatorrhoea) but has limited
      sensitivity for the detection of mild cases. With regard to the higher
      sensitivity and specificity, the higher practicability, and the much lower cost,
      determination of faecal elastase 1 concentrations is superior to the 13C-mixed
      triglyceride breath test and therefore remains the most reliable indirect
      pancreatic function test available today.

PMID- 9548630
TI  - Retention in an aftercare program for recovering women.
AB  - Examining the correlates of aftercare participation is critical to program
      development and successful relapse prevention. This study assesses retention in
      an aftercare program of case management and peer support for formerly homeless
      recovering mothers. Length of residential drug treatment, length of sobriety,
      strong support networks, and concerns about housing and parenting predicted
      completion of the case management component. Emotional instability and the
      severity of problems were found to be correlated with participation in the peer
      support group. Sociodemographic characteristics were not related to program
      retention. The findings illustrate the need to tailor aftercare services to the
      level of clients' recovery and the need for female-only aftercare groups where
      women can safely discuss physical and sexual abuse issues related to their misuse
      of drugs.

PMID- 9548631
TI  - Computer-based smoking cessation interventions in adolescents: description,
      feasibility, and six-month follow-up findings.
AB  - The impact of adolescent smoking cessation clinics has been disappointing due to
      low participation rates, high attrition, and low quit rates. This paper describes
      two computerized self-help adolescent smoking cessation intervention programs: 1)
      a program utilizing the expert system which is based on the transtheoretical
      model of change and 2) a popular action-oriented smoking cessation clinic program
      for teens which was modified for computer presentation. High participation rates
      in the program among 132 smokers demonstrate the high feasibility and
      acceptability of the programs. Quit rates of up to 20% were observed during the
      intervention, and an additional 30% made unsuccessful quit attempt(s). The 6
      month follow-up findings indicated that adolescents were poorly prepared to
      maintain abstinence.

PMID- 9548632
TI  - The role of intergenerational discrepancy of cultural orientation in drug use
      among Latina adolescents.
AB  - The role of intergenerational discrepancy for cultural orientation was examined
      in the etiology of drug use among Latina adolescents and in the context of family
      support. Intergenerational discrepancy occurs when a family member of one
      generation differs from a family member of another generation in cultural
      identity factors; this is usually manifested in conflict between a first
      generation child and the immigrant generation parent. It was hypothesized that
      the Latina adolescents experiencing intergenerational discrepancy might use drugs
      more frequently than Latina adolescents who were not; and that family support
      would be an important moderator of the relationship. A sample of 295 ninth and
      tenth grade Latina students (approximately 80% Mexican-American) from four Los
      Angeles area schools were surveyed as part of a larger study. In this secondary
      analysis, a 2 (family support ) x 2 (discrepancy) ANOVA revealed that
      intergenerational discrepancy was associated with more drug use in certain cases,
      and that family support did not moderate this relationship. Results partially
      validate and extend a theoretical model presented by Szapocznik and Kurtines
      (1980), and indicate a need to focus on cultural variables when intervening in
      drug use/misuse among Latina adolescents.

PMID- 9548633
TI  - Primary socialization theory: the etiology of drug use and deviance. I.
AB  - The fundamental theorem of primary socialization theory is that normative and
      deviant behaviors are learned social behaviors, products of the interaction of
      social, psychological, and cultural characteristics, and that norms for social
      behaviors, including drug use, are learned predominantly in the context of
      interactions with the primary socialization sources. During adolescence, learning
      of social behaviors is frequently dominated by interactions with peer clusters.
      There are a number of additional postulates: 1) The strength of the bonds between
      the youth and the primary socialization sources is a major factor in determining
      how effectively norms are transmitted. 2) Any socialization link can transmit
      deviant norms, but healthy family and school systems are more likely to transmit
      prosocial norms. 3) Peer clusters can transmit either prosocial or deviant norms,
      but the major source of deviant norms is usually peer clusters. 4) Weak
      family/child and/ or school/child bonds increase the chances that the youth will
      bond with a deviant peer cluster and will engage in deviant behaviors. 5) Weak
      peer bonds can also ultimately increase the changes of bonding with deviant
      peers. Primary socialization theory is consistent with current research, has
      strong implications for improving prevention and treatment, and suggests specific
      hypotheses for further research.

PMID- 9548634
TI  - Effectiveness of a drug-free detention treatment program in a Dutch prison.
AB  - Several Dutch penitentiaries, which have relatively severe drug-use related
      problems, experimented with drug-free detention treatment programs (DVA). These
      programs aim at controlling drug use by offering a therapeutic atmosphere and
      serve as linkage to detention posttreatment. In a Rotterdam jail (335 cells), ca.
      10% were the DVA. Information was gathered from 86 male inmates who volunteered
      to enter the program, and 42 from other wings. After 1 year the drug-free
      detention group more actively searched and accepted treatment. No differences
      were found in drug use, recidivism, or physical, social, and psychological
      problems.

PMID- 9548635
TI  - Classification of developmental delays.
AB  - Developmental delay is frequently used to identify children with delay in meeting
      developmental milestones in one or more streams of development. There is no
      consensus on the specific definition. Developmental delay is best viewed
      generically as a chief complaint rather than a diagnosis. A child suspected to
      have delays should always be assessed in each of the major streams of
      development: expressive and receptive language, including social communication;
      visual problem solving (nonverbal cognition); motor development; neurobehavioral
      development; and social-emotional development. A model developed by the National
      Center for Medical Rehabilitation Research is used to compare existing
      classifications of developmental delays. This model defines the five domains in
      the disability process: pathophysiology, impairment, functional limitation,
      disability, and societal limitation. An etiology domain is added. This model is
      used to illustrate how existing classification systems of cerebral palsy, mental
      retardation, autism, and language delay draw on information from one or more
      domains. The model illustrates some of the conflicts between different systems.
      For example, most classification systems for cerebral palsy emphasize only
      impairment (spasticity, dyskinesias, and topography). The current definition and
      classification system for mental retardation focuses on functional limitations
      (IQ), disability, and societal limitations, ignoring pathophysiology and details
      of impairment. Given the complexity of neurodevelopmental disabilities, it is
      unlikely that a single classification system will fit all needs.

PMID- 9548636
TI  - The etiology of developmental delay.
AB  - Developmental delay includes mental retardation (IQ less than 70) and borderline
      intellectual functioning (IQ 71 to 84). The overall frequency is between 1% and
      2% of the child population with most cases in the mild range (IQ 50 to 70).
      Severe mental retardation is mostly due to genetic or acquired biological causes.
      Mild retardation is more commonly of acquired causes, and in borderline
      intellectual functioning, sociocultural factors play a role in addition to
      biological factors. The main prenatal causes include chromosomal and
      nonchromosomal genetic conditions, metabolic disorders, and adverse events during
      gestation, whereas environmental factors (eg, alcohol) more commonly cause mild
      retardation.

PMID- 9548637
TI  - The evaluation of the child with a global developmental delay.
AB  - The child with a global developmental delay presents a diagnostic challenge to
      the practitioner. The spectrum of possible etiologic diagnosis and laboratory
      investigations that could be pursued are quite extensive. This article presents
      the rationale for diagnostic testing in this population and provides guidelines
      to those tests that should be pursued.

PMID- 9548638
TI  - Screening tests and standardized assessments used to identify and characterize
      developmental delays.
AB  - The appropriate choice, application, and interpretation of functional assessments
      of children with problems of development are often challenging issues for
      clinicians. The purposes of this communication are to share with clinicians an
      understanding of the structure and properties of functional assessment measures;
      to offer an orientation to the application of such measures to help evaluate a
      child's developmental status; and to suggest issues that are important to
      consider in the interpretation of the findings, and how these might be shared
      with parents. Numerous references are cited for readers who wish to read more
      about measures in general and about specific clinical assessment tools that are
      most useful in applied child development.

PMID- 9548639
TI  - Radiological findings in developmental delay.
AB  - This article reviews the neuroimaging findings in patients with nonsyndromic
      mental retardation and global developmental delays. The frequency and type of
      abnormal neuroimaging findings in this patient population are discussed.
      Specifically addressed are the issues of which patients should have neuroimaging
      studies in light of (in the vernacular) "cost-benefit" analysis. The extension of
      these studies to "milder" developmental delays, and other neurodevelopmental
      disorders are also discussed.

PMID- 9548640
TI  - Genetics and developmental delay.
AB  - The discovery of new cytogenetic and molecular genetic techniques and principles
      has been explosive in recent years. A secure diagnosis based on molecular
      evidence has become possible for many syndromes previously only clinically
      defined, which has helped enormously in predicting children's developmental
      progress, in allowing knowledgeable surveillance for potential associated health
      problems, in genetic counseling, and in prenatal diagnosis. This article reviews
      several of the most significant recently described cytogenetic and molecular
      genetic principles and techniques in relation to the child who presents with
      developmental delay.

PMID- 9548641
TI  - Electroencephalogram in developmental delay: specific electroclinical syndromes.
AB  - The electroencephalogram (EEG) plays an important role in the evaluation of a
      child with developmental delay. An EEG is often required to classify seizures in
      children with developmental delay. Equally important is the role of the EEG in
      the identification of specific electroclinical syndromes in children who may or
      may not manifest seizures. Specific electroclinical syndromes include the
      acquired epileptiform aphasia syndrome, Landau-Kleffner syndrome, and electrical
      status epilepticus during slow wave sleep. Other clinical situations where the
      EEG offers diagnostic and prognostic information, such as subacute sclerosing
      encephalitis, progressive myoclonus epilepsies, Rett syndrome, and Lennox Gastaut
      syndrome are also discussed.

PMID- 9548642
TI  - The vulnerable preschool child: the impact of biomedical and social risks on
      neurodevelopmental function.
AB  - The scope of preschool children with biological risk and social disadvantage is
      large and includes over 1 million (28%) newborns per year. Currently in 1996, 7%
      of children are born with low birth weight, 1% are born with very low birth
      weight, 20% have alcohol exposure, and 10% have other drug exposure. Poverty is
      dynamic and impacts on 25% of children less than 6 years old with increased
      frequency in children who are minority, have mothers with less than a high school
      education, or are unmarried. There has been a markedly increased survival in very
      low birth weight and extremely low birth weight infants in the past 10 years.
      Outcomes of these neonatal populations reveals that parenchymal brain injury is
      the major predictor of cerebral palsy which occurs in 7% to 10% of very low birth
      weight survivors. However, poverty is the major predictor of low IQ. Fetal
      alcohol syndrome occurs in 1.9 per 1,000 births and is most often associated with
      mild mental retardation and educational underachievement. Studies investigating
      cocaine revealed that it is a multifactorial problem overlapping with
      polysubstance abuse and other risk factors for social disadvantage. The
      overwhelming number of children do not have cerebral palsy or severe mental
      retardation. The long-term impact is more subtle and needs more systematic
      analysis as well as critical evaluation of cognitive impairments and educational
      under-achievement. Hypoxic ischemic encephalopathy (HIE) cannot be determined by
      one biological measure. Though multiple disability occurs in 70% of children with
      Sarnat stage 3 HIE, 30% of survivors are not disabled. Children with mild to
      moderate HIE have long-term outcomes that are influenced by 9- to 12-month
      neurodevelopmental status and social disadvantage. By combining strategies to
      lessen biological risks and enhance developmentally appropriate environments,
      long-term outcomes of preschool children can be optimized.

PMID- 9548643
TI  - Benefits of early intervention for children with developmental disabilities.
AB  - Early intervention programs are designed to enhance the developmental competence
      of participants and to prevent or minimize developmental delays. Children
      targeted for early intervention may either include environmentally or
      biologically vulnerable children, or those with established developmental
      deficits. There is growing consensus based on the best available evidence that
      early interventions can exert moderate positive effects. However, this literature
      is limited by substantial methodological weaknesses in most studies. Therefore
      further randomized clinical trials are needed to ascertain which programs best
      meet the needs of children with or at risk for developmental disability.

PMID- 9548644
TI  - Clinical ethics and developmental delay.
AB  - The vulnerability of the young child with a developmental delay raises specific
      concerns regarding the provision of medical care to this population. Specific
      areas of concern include the means and standards by which a valid consent for
      intervention is obtained and exercised, as well as the issue of justice that
      refers, in this context, to the distribution of what are increasingly perceived
      as scarce medical and economic resources. Furthermore, future advances in
      providing care to this population will need to be predicated on clinical research
      that needs to be ethically sound. This article highlights basic ethical
      principles and their application to these specific issues with respect to
      children with developmental delay.

PMID- 9548645
TI  - The water absorption response: a behavioral assay for physiological processes in
      terrestrial amphibians.
AB  - Terrestrial amphibians take up water by abducting the hind limbs and pressing a
      specialized portion of the ventral skin to a moist surface, using a
      characteristic behavior called the water absorption response. An assay of the
      water absorption response was used to quantify physiological factors associated
      with thirst and water uptake. Dramatic changes in the water absorption response
      resulted from subtle changes in hydration state and from altering the reserve
      water supply in the urinary bladder. The water absorption response could be
      induced by intraperitoneal and intracerebroventricular injection of angiotensin
      II, demonstrating that components of the renin-angiotensin system on both sides
      of the blood-brain barrier have a dipsogenic function in amphibians. These
      experiments also demonstrated that the water absorption response could be
      influenced by changes in barometric pressure. Toads avoided the water absorption
      response on hyperosmotic substrates, and behavioral experiments showed that the
      amphibian skin served a sensory function similar to that of the lingual
      epithelium of mammals. The water absorption response assay has enormous potential
      as a tool for the investigation of physiological processes and sensory
      capabilities of amphibians.

PMID- 9548646
TI  - Plasma corticosterone and testosterone levels during the annual reproductive
      cycle of male brown anoles (Anolis sagrei).
AB  - The objective of the present study was to determine the plasma levels of
      testosterone and corticosterone in male Anolis sagrei during the annual
      reproductive cycle and to examine the relationships between seasonal change in
      the levels of these hormones, male reproductive activity, and body condition.
      Both testosterone and corticosterone levels in adult males captured in the Miami,
      Florida, area varied significantly with month and with season (i.e., breeding vs.
      nonbreeding period), although they were not significantly correlated with each
      other or with body mass. Mean monthly testosterone levels were higher during the
      breeding season (March-August) than during the nonbreeding season, with the one
      exception that the highest mean testosterone level occurred in February
      immediately before the beginning of the breeding season. Testosterone levels in
      the overall sample of 144 males were significantly correlated with testes mass
      but not with any of the other measured variables. Corticosterone levels were
      highest during the nonbreeding season and lowest during the breeding season.
      Corticosterone levels on a monthly basis were negatively correlated with monthly
      changes in testes mass and positively correlated with monthly changes in
      abdominal fat-body mass.

PMID- 9548647
TI  - Daily energy budgets of avian embryos: the paradox of the plateau phase in egg
      metabolic rate.
AB  - The metabolic rate of precocial bird eggs reaches a plateau when about 80% of the
      incubation period has passed. This is unexpected, as in many species the embryo
      continues to grow and maintenance costs must therefore increase. To investigate
      this paradox, daily energy budgets were constructed for embryos of four galliform
      species according to two models that used empirical data on egg metabolic rate
      and embryo growth. In the first model, embryonic synthesis costs were estimated,
      with an assumed synthesis efficiency, before calculating the maintenance costs.
      In the second model, embryonic maintenance was calculated first, and no
      assumptions were made on the synthesis efficiency. The calculations show that
      assumptions of the synthesis efficiency had a major impact on the energy budget
      calculations, because embryonic growth rate was high. During the plateau phase, a
      galliform embryo allocated energy in favor of its maintenance costs in three
      ways: by decreasing growth rate, by increasing synthesis efficiency, and by
      depressing the formation of glycogen. Our study suggests that a reduction in
      growth rate plays a minor role. An increase of synthesis efficiency is more
      likely to explain the plateau in energy expenditure, since small increases in
      synthesis efficiency can lead to great savings on synthesis costs.

PMID- 9548648
TI  - Echocardiographic and hemodynamic determinations of the ventricular filling
      pattern in some teleost fishes.
AB  - The current concept of ventricular filling in elasmobranch and teleost fishes is
      that atrial contraction is the primary, if not the exclusive, determinant of
      ventricular filling. Recent echocardiographic and on-line hemodynamic data for
      elasmobranchs, however, have demonstrated a biphasic ventricular filling pattern,
      characterized by an early phase that occurs during ventricular relaxation and a
      late phase that follows atrial systole. This study reports echocardiographic and
      hemodynamic analyses of ventricular filling in three teleost genera (Paralabrax,
      Channa, Monopterus) having markedly different heart morphologies. Both the
      profiles of the atrioventricular pressure gradient in Paralabrax and the
      ventricular inflow velocity in all three genera indicate a biphasic ventricular
      filling pattern. Although the relative contribution of the early and late filling
      phases differed among the species studied, interspecific differences in heart
      structure did not obscure the biphasic pattern. Also, pericardiectomy did not
      affect the biphasic ventricular filling pattern in Paralabrax. The presence of
      biphasic filling in teleosts establishes a functional similarity with the
      elasmobranchs and, because the biphasic ventricular filling pattern predominates
      in higher vertebrates, suggests that this ventricular filling mechanism may be
      present in the entire subphylum Vertebrata.

PMID- 9548649
TI  - Test of a digestion optimization model: effects of costs of feeding on digestive
      parameters.
AB  - We tested predictions of a chemical reactor model of digestion by manipulating
      the short-term costs of feeding and then measuring the effect on digestive
      parameters. We compared residence time of digesta and extraction efficiency of
      glucose in cold-acclimated waxwings (Bombycilla cedrorum) feeding ad lib. and in
      birds whose costs of feeding were increased through the addition of intervals of
      time when they received no food. Such a feeding schedule simulated the ecological
      situation in which a frugivorous bird like a waxwing encounters food in patches
      and experiences nonfeeding periods as it searches for new preferred food patches.
      None of the results were consistent with the predictions of the optimal digestion
      model: extraction efficiency was independent of costs of feeding, and residence
      times did not increase as costs of feeding increased. This empirical evidence on
      the passage of digesta in waxwings suggests that movement of digesta in the guts
      of birds is much more complex than movement of material in an ideal chemical
      reactor. Tests of the optimal digestion model have involved manipulating food
      quality or the costs of feeding, and the conclusions are similar: compensatory
      modulation of retention time or digesta mixing and not rate of hydrolysis and
      absorption seem most important in maintaining the remarkably constant digestive
      efficiency.

PMID- 9548650
TI  - Ionic regulation and nitrogenous excretion in rainbow trout exposed to buffered
      and unbuffered freshwater of pH 10.5.
AB  - Rainbow trout exposed to unbuffered water of pH 10.5 initially showed significant
      increases in blood pH, plasma cortisol and glucose, partial pressure of NH3
      (PNH3), NH4+, and HCO3- values as well as loss of plasma Cl-, reduced partial
      pressure of CO2 (PCO2), and inhibition of total ammonia excretion rate. After the
      first day, fish resisted further change, and new levels were established (for
      blood pH and plasma PCO2 and PNH3 levels) or imbalances corrected, either
      partially (for total ammonia excretion) or completely (for plasma Cl-, HCO3-,
      cortisol, and glucose values). During the 7-d exposure, 80% of fish in unbuffered
      water survived, but in buffered water (0.75 mmol L(-1) glycine-buffered KOH at pH
      10.5), survival was only 50% after 3 d, and ion regulatory failure was evident.
      Fish in buffered and unbuffered alkaline waters had similar total ammonia
      excretion rates, which suggests that glycine-buffered KOH was not sufficient to
      significantly reduce gill boundary layer acidification. After 7 d in unbuffered
      alkaline water, 30% of total ammonia excretion was linked with an amiloride
      sensitive (0.1 mmol L(-1)) Na+ uptake mechanism. Treatment of alkaline-exposed
      trout with waterborne acetazolamide (1.5 mmol L(-1)) indicated that gill boundary
      layer H+ production, through hydration of CO2, had a role in excretion of total
      ammonia. Exposure to 4-acetamino-4'-isothiocyantostilbene-2,2'-disulphonic acid
      (SITS; 0.1 mmol L(-1)) following 24-h exposure to unbuffered alkaline water
      resulted in increased plasma HCO3- and lowered plasma Cl- concentrations,
      indicating the role of branchial Cl-/HCO3- exchange in regaining Cl- lost and
      eliminating the HCO3- accumulated during exposure to alkaline water.

PMID- 9548651
TI  - The effect of body mass and temperature on the heart rate, stroke volume, and
      cardiac output of larvae of the rainbow trout, Oncorhynchus mykiss.
AB  - The goal of this experiment was to determine whether the type of tight supply-and
      demand relationship between cardiac output and metabolic demand for O2 seen in
      juvenile and adult fish applies during larval development. To this end, we looked
      at how the heart rate, stroke volume, and cardiac output of rainbow trout
      (Oncorhynchus mykiss) larvae varied in response to changes in tissue mass and
      incubation temperature. Previous studies have shown that both factors have a
      profound influence on metabolic rate. Heart rate and stroke volume were estimated
      using videomicroscopic methods and used to calculate cardiac output at five or
      six approximately evenly spaced intervals between hatch (approximately 15 mg wet
      tissue mass) and 150 accumulated thermal units (degrees C d) posthatch
      (approximately 50 mg tissue mass) at 5 degrees, 10 degrees, 12 degrees, and 15
      degrees C. Cardiac output (range 0.2-20 microL min(-1)) increased significantly
      in response to increases in both tissue mass and incubation temperature. The
      increase in cardiac output with tissue mass reflected significant increases in
      stroke volume as well as heart rate. Temperature only had a significant effect on
      heart rate (i.e., stroke volume was unaffected). The rate of increase in cardiac
      output as a result of tissue growth was significantly faster than the rate at
      which O2 demand increased (the allometric mass exponent [+/-SE] for cardiac
      output was 1.78 +/- 0.08; literature values for O2 uptake average approximately
      1.0), which suggests that the cardiovascular system was less important as a means
      of delivering O2 to the tissues in small larvae than it was in larger larvae and
      in juvenile and adult fish. Direct diffusion appeared to be the primary means of
      O2 delivery in small larvae and embryos.

PMID- 9548652
TI  - Comparative development in captive and migratory populations of the barnacle
      goose.
AB  - The development of the locomotory muscles and associated skeletal structures of
      goslings and adults from a captive population of barnacle geese (Branta
      leucopsis) was compared with that from a wild migratory population. There was no
      significant difference between flight-muscle development of wild and captive
      goslings up to 7 wk of age, when the birds are first able to fly. In contrast,
      mass-specific citrate-synthase activity in the semimembranosus leg muscle of the
      captive goslings was significantly lower than that of wild goslings by 5 wk of
      age. During the postfledging premigratory period, captive geese showed
      significantly higher values for both mass and mass-specific citrate-synthase
      activity of the leg muscles than those of wild birds. Premigratory wild geese had
      significantly higher citrate-synthase activity in the pectoralis muscles and
      larger cardiac ventricular mass (by ca. 20%-25%) than both wild postmoulting and
      captive premigratory adults. Total flight-muscle mass was only slightly reduced
      (by ca. 10%) in long-term captive adults compared with wild premigratory adults.
      Most of the differences between these two populations appear primarily to reflect
      their relative levels of activity and/or differences in their ambient
      environment, rather than any intrinsic differences in developmental or adult
      physiology.

PMID- 9548653
TI  - Blood volume and diving ability of the New Zealand sea lion, Phocarctos hookeri.
AB  - We test the hypothesis that the New Zealand sea lion is physiologically better
      equipped for prolonged, continuous diving than other otariids (fur seals and sea
      lions) by measuring its blood volume, an important component of its oxygen
      storage. Mass, hematocrit, and plasma volume were measured and blood volume
      calculations were completed on 14 adult females and five juvenile females. Plasma
      volume was determined using the Evans blue dye dilution technique. Mean plasma
      volume for all subjects was 74 mL kg(-1). Mass-specific plasma volume was
      significantly higher in adult females (15.3%) than in juveniles (14.6%). Blood
      volume (150 mL kg(-1)) and hematocrit (51%) were not significantly different
      between adults and juveniles. The aerobic dive limit can be estimated by dividing
      the animal's oxygen stores by its metabolic rate. The estimated aerobic dive
      limit for adult animals was between 5.5 and 7.8 min, depending on the assumed
      metabolic rate. New Zealand sea lions have the highest blood volume yet reported
      for an otariid, which supports the hypothesis that they have a physiological
      capability suited to their unique diving behavior.

PMID- 9548654
TI  - Regulation of water and sodium balance in the field by Australian honeyeaters
      (Aves: Meliphagidae).
AB  - We evaluated the use of water and sodium by free-living individuals of several
      species of Australian honeyeaters (Acanthorhynchos superciliosus, Phylidonyris
      novaehollandiae, Phylidonyris nigra, Manorina flavigula, and Anthochaera
      carunculata). Water and Na fluxes were highly variable between species, largely
      reflecting differences in diet. Water fluxes ranged from approximately 300% of
      total body water per day in 10-g, nectarivorous A. superciliosus to approximately
      45% of total body water per day, typical of a desert species, in M. flavigula, a
      50-g, insectivorous, arid-zone bird. Similarly, Na fluxes ranged from nearly 60%
      of Na pool per day in A. superciliosus to about 25% per day in M. flavigula.
      Despite these different fluxes, values of regulated osmoregulatory variables,
      including plasma osmolality, hematocrit, plasma concentrations of Na+ and K+, and
      exchangeable Na pool, were relatively invariant both between species and within
      species at different seasons. In contrast, values of variables reflecting the
      operation of regulatory systems did differ between species and seasons. Urine
      concentrations were highest in M. flavigula and, in A. carunculata, varied
      seasonally (higher in summer than winter). Plasma concentrations of aldosterone
      were lowest in A. carunculata (5-25 pg/mL), highest in P. novaehollandiae (70-200
      pg/mL), and in the latter species were higher in winter than summer.
      Concentrations of arginine vasotocin ranged from 5 pg/mL in A. carunculata to
      greater than 30 pg/mL in M. flavigula. Our data demonstrate that within the
      family Meliphagidae, there exists substantial variation in the fluxes of water
      and Na and that these relate in part to body size variation but more importantly
      to diet. The different fluxes between species are reflected in the values of
      numerous osmoregulatory variables.

PMID- 9548655
TI  - Dietary flexibility and intestinal plasticity in birds: a field and laboratory
      study.
AB  - The adaptive modulation hypothesis posits that the expression of digestive
      proteins should be modulated in response to intake of their respective
      substrates. A corollary of this hypothesis suggests that dietary flexibility and
      digestive plasticity should be correlated. We examined these two hypotheses in
      two granivorous Chilean birds (Zonotrichia capensis and Diuca diuca) that differ
      in dietary breadth. D. diuca is a strict granivore, whereas Z. capensis also eats
      insects. In field-caught birds, the activity of the intestinal dipeptidase
      aminopeptidase-N was positively correlated with intake of insects in Z. capensis
      but not in D. diuca. This is the first field documentation of modulation of
      intestinal enzymes by diet in birds. Intestinal maltase and sucrase activities
      were not correlated with seed (vs. insect) intake in either species. In the
      laboratory, captive birds of both species exhibited similar modulation of
      membrane-bound intestinal hydrolases when fed on synthetic diets of contrasting
      carbohydrate and protein composition. Maltase, sucrase, and aminopeptidase-N
      activities were significantly higher in birds fed on the carbohydrate-free than
      those on the carbohydrate-containing diet. Activities of the three enzymes were
      positively correlated. Therefore, this increase probably resulted from
      nonspecific increases of all enzymes resulting from intake of the carbohydrate
      free diet. Principal components analysis separating the effect of diet on
      specific and on nonspecific modulation revealed that diet had a strong effect on
      nonspecific activity of intestinal enzymes in both Z. capensis and D. diuca. Diet
      also significantly affected aminopeptidase-N activities when the effect of diet
      on nonspecific modulation was removed. Birds fed on the carbohydrate-free, high
      protein diet had significantly higher specific aminopeptidase-N activities than
      those fed on the carbohydrate-containing diet. Our results cast doubts on the
      notion that dietary flexibility and the plasticity of the gut's enzymes are
      necessarily correlated and on the general validity of the adaptive modulation
      hypothesis.

PMID- 9548657
TI  - Pancreatology in Japan: historical development--an overview.

PMID- 9548656
TI  - Development of thermoregulation and posthatching growth in the altricial
      cockatiel Nymphicus hollandicus.
AB  - The development of thermoregulation and growth during the nestling period of
      cockatiel Nymphicus hollandicus were examined in this study. It was hypothesised
      that, in comparison to other altricial species of similar body mass, cockatiel
      chicks develop endothermy earlier and consequently have less energy available for
      growth, resulting in reduced growth rates. While poorly insulated and blind at
      hatching, cockatiel developed endothermic responses in their first week, and were
      individually effectively homeothermic (with 75% of adult ability to maintain body
      temperature during exposure to 20 degrees-25 degrees C), by maintaining high
      metabolic rates (at all ambient temperatures tested) above the predicted resting
      rates of an adult of similar body mass before parental brooding ceased (12-13 d).
      Mass-independent metabolic rates were equivalent to those of fledglings at only
      20% of the nestling period (37 d), well before adequate insulation was obtained.
      The Gompertz growth constants of cockatiel were significantly lower than those of
      other altricial land birds, which supports the hypothesis of this study.

PMID- 9548658
TI  - Pancreatic surgery in Japan: historical review.
AB  - The advent of surgical techniques for the management of pancreatic cancer has had
      a long and varied history in the Western culture. The development of current
      surgical techniques and treatment modalities is based on (rooted in) techniques
      developed over time. Although the first written anecdotes of pancreatic resection
      -primarily from the 1600s through the late 1800s--did not alter the mortality of
      pancreatic cancer, they did pave the way for advances in surgical techniques that
      subsequently attained lower morbidity and mortality rates. Although there were
      some meager attempts at pancreatic resection in Japanese institutions before and
      during World War II, it was not until after the war, and particularly after the
      mid-1950s, that pancreatic surgery developed tremendously. The development of
      more radical approaches to pancreatic surgery developed tremendously. The
      development of more radical approaches to pancreatic resection as well as other
      surgical developments resulted in lower morbidity and mortality rates.

PMID- 9548659
TI  - Pancreatic surgery: cutting-edge developments and technology.
AB  - In the 1980s, Japanese pancreatic surgeons used aggressive strategies to treat
      pancreatic cancer under the influence of Fortner's regional pancreatectomy and
      developed several surgical approaches including extended lymph node and
      connective tissue clearance with autonomic nerve dissection around the celiac and
      superior mesenteric arteries. Nagakawa's "translateral retroperitoneal approach"
      in extended radical pancreatectomy was accepted and used by many Japanese
      surgeons; however, whereas this operation prolonged postoperative survival, it
      also induced high rates of postoperative complications and ultimately failed to
      improve the quality of the patient's life. A pylorus-preserving
      pancreatoduodenectomy with modified extended dissection of the lymph node and
      connective tissues did not decrease the survival rate for resected patients but
      improved their quality of life. In the next decade, Takada developed duodenum
      preserving total pancreatic head resection, which preserves the integrity of the
      digestive and biliary tracts. This operation, to anastomose the main pancreatic
      duct with the duodenum, is unique and is applicable to benign or low-grade
      malignant lesions of the pancreas. Adjuvant treatments have not offered
      satisfactory results as expected. Finally, it is recommended that the aggressive
      Japanese surgical strategies be reevaluated in a formal trial with a prospective
      randomized study to improve the quality and longevity of the patients' lives.

PMID- 9548660
TI  - The epidemiology of pancreatic diseases in Japan.
AB  - We reviewed the trends and death rates of pancreatic cancer and pancreatitis in
      Japan over the past four decades. It is a disturbing fact that the death rate due
      to pancreatic cancer is rising, parallel to that of lung cancer and colon cancer
      and that it is affecting primarily the elderly 65 years and older in both sexes.
      The cause of this increase is partially attributable to improvements in the
      diagnosis, changes in life-style, and smoking. The death rate due to chronic and
      acute pancreatitis has remained constant during the past four decades.

PMID- 9548661
TI  - Japan Pancreatic Cancer Registry: current status.
AB  - The Pancreatic Cancer Registration Committee of the Japan Pancreas Society
      registered a total 17,130 patients with pancreatic cancer from 350 major
      hospitals in Japan from 1981 through 1995. Diagnosis with ultrasonography and
      computed tomography has become increasingly important as the methods used for
      first detecting a pancreatic lesion. Tumor resection was performed in 36% of the
      patients, and the 5-year survival rate of the patients who received resection was
      18.2%. The rate of resection and results of surgical treatment have improved,
      which may be attributed to the increase in detection of resectable tumor and
      benefits of aggressive and extended surgery.

PMID- 9548662
TI  - Criteria for diagnosis of acute pancreatitis in Japan and clinical implications.
AB  - The Japanese grading system for severity of acute pancreatitis has evolved from
      results of a national survey on 2,553 patients managed in 523 major medical
      centers in Japan between 1982 and 1986. It was devised to embrace the predictive
      factors that would offer high sensitivity and specificity in rendering an
      accurate diagnosis. In this system, computed tomographic (CT) examination is used
      for estimating the severity of acute pancreatitis. Combining criteria from
      laboratory data, clinical signs, and CT findings, the system appears cumbersome.
      However, it is actually more flexible in that only few criteria, from the wide
      range of findings actually covered, are needed to predict severity. Its rationale
      stems from a national effort to improve the outcome of this life-threatening
      disease. Further prospective studies are needed to determine its accuracy and
      superiority.

PMID- 9548663
TI  - Criteria for pancreatic disease diagnosis in Japan: diagnostic criteria for
      chronic pancreatitis.
AB  - Chronic pancreatitis was not a clinical entity until around 1960 in Japanese
      gastroenterology. The diagnosis of chronic pancreatitis had been vague and
      difficult to ascertain. The diagnostic criteria for chronic pancreatitis were
      first proposed in 1971, and they were subsequently revised in 1983. Patient
      numbers of chronic pancreatitis were summed by national surveys under each of the
      common diagnostic criteria. Total patient number and incidence rate of chronic
      pancreatitis are recognized as increasing throughout Japan, based on results of
      two national surveys of chronic pancreatitis. The diagnostic criteria for chronic
      pancreatitis in Japan were again revised in 1995, because the 1983 criteria were
      too complicated, and there had been more recent progress in clinical
      investigations of the pancreas. The essential revised points of the Diagnostic
      Criteria, 1995, are introduced in this review along with some discussion.

PMID- 9548664
TI  - Stage classifications of pancreatic cancer: comparison of the Japanese and UICC
      classifications and proposal for a new staging system. Union Internationale
      Contre le Cancer.
AB  - In the 4th edition of General Rules for the Study of Pancreatic Cancer by the
      Japan Pancreas Society (JPS), published in 1993 (English version published in
      1996), a system resembling the TNM classification by the Union Internationale
      Contre le Cancer (UICC) was adopted, based on the results of precise analysis of
      data from 11,317 cases of carcinoma of the pancreas registered by the JPS during
      the 10-year period from 1981 to 1990. We compare the two TNM classifications and
      staging groups, focusing on the simplicity and reproducibility of the diagnostic
      criteria and the reliability of predicting outcome. To compare the prognostic
      value of the two classification systems, we analyzed the published data on
      resected cases registered by Pancreatic Cancer Registration Committee of the JPS.
      The results showed that a major drawback of the JPS classification is that is
      difficult to apply and has poor reproducibility. Survival rates differed
      significantly among the four stages in the JPS classification, whereas the UICC
      staging system did not reflect differences in outcome among the four stages,
      especially between stages II and III. The prognostic value of the UICC T category
      is better than that of the JPS T category, whereas the N category of JPS has
      better prognostic value than that of the UICC system. Believing that a
      combination of the two systems would solve this problem, we propose a new TNM
      classification and stage-grouping system that draws on the merits of both. This
      new system may provide improvements in staging classification that will lead to
      the establishment of a more practical and universal staging system for ductal
      carcinoma of the pancreas.

PMID- 9548665
TI  - Exocrine pancreatic physiology: overview.
AB  - Exocrine pancreatic physiology has been actively investigated in Japan during the
      past 30 years. We selected three areas and reviewed them for this article. The
      selected areas are perfusion of the isolated pancreas, cholecystokinin (CCK)
      releasing factor from pancreatic juice (monitor peptide), and genetically
      diabetic rats. The aim of this article is to present a brief overview of the
      selected areas of exocrine pancreatic physiology in Japan so that future research
      can be productively directed.

PMID- 9548666
TI  - Ca2+ signaling in the pancreatic acinus.
AB  - Change in cytosolic free calcium ion concentration [Ca2+]c, resulting from
      receptor activation by an appropriate agonist, functions as a cardinal
      intracellular signaling in the stimulus-secretion coupling in a wide variety of
      secretory cells including the acini of the pancreas. Ratiometric imaging of
      [Ca2+]c dynamics by UV-laser scanning confocal microscopy led us to conclude that
      in the cholecystokinin (CCK)-8-induced recurrent [Ca2+]c, spiking increases
      initially in the basolateral margin of the acinus and propagates to the luminal
      margin. [Ca2+]c in this initial cell increased rapidly and uniformly to the
      maximum level. The decrease in [Ca2+]c in the initial cell coincided with a small
      increase in [Ca2+]c in the luminal regions of the bilateral neighboring cells
      followed by uniform maximal increase in [Ca2+]c in these neighboring cells. A
      series of [Ca2+]c dynamics was repeated to form recurrent Ca2+ spiking. The
      temporal sequences of [Ca2+]c dynamics recorded during continuous stimulation
      with CCK-8 at a physiologic concentration in individual acinar cells forming the
      acinus were displayed on the identical time scale. The figure indicates that the
      signaling is not synchronous in cells forming an acinus. From these and other
      results, we proposed a model in which CCK-8 at a low physiologic concentration
      binds to highly sensitive CCK receptor interacting with heterotrimeric guanosine
      5'-triphosphate-binding proteins of the Gq class, generate Ins 1,4,5-P3, and
      recurrent [Ca2+]c, spiking. The recurrent Ca2+ spiking maintains a sustained
      secretory response, recurrent exocytosis of zymogen granules, and concomitant
      secretion of isotonic NaCl.

PMID- 9548667
TI  - Luminal feedback regulation, monitor peptide, CCK-releasing peptide, and CCK
      receptors.
AB  - We summarize the discovery of luminal feedback regulation of pancreatic secretion
      in rats and its history. In rats, removal of proteolytic activity from the
      intestine produced a significant increase in pancreatic protein (enzyme) output.
      This increase was confirmed to be mediated by circulating cholecystokinin (CCK).
      Subsequently, two CCK-releasing peptides, monitor peptide and luminal CCK
      releasing factor (LCRF), were purified from the rat pancreatic juice and small
      intestine, respectively, to elicit CCK release in luminal feedback regulation.
      Furthermore, we emphasize the important physiologic roles of CCK and CCK
      receptors by the discovery of disrupted CCK-A-receptor gene in rats. These
      findings should help to determine the regulation of pancreatic secretion and CCK
      functions in humans.

PMID- 9548668
TI  - A new model for pancreatitis.
AB  - Pancreatitis induced by ligation of the pancreatic duct produces morphologic
      similarities to human pancreatitis. This model is easily performed in big
      animals, but it is very difficult to perform pancreatic duct ligation in small
      animals. Many experimental studies of pharmaceutical treatments for pancreatitis
      used pancreatic duct-ligation models, but it is also difficult to evaluate the
      efficacy of the drugs used, because the animals used are of different species
      with individual differences. To overcome these problems, we ligated the main
      pancreatic duct of the splenic lobe by a 5.0 absorbable suture by using a
      surgical microscope and left the gastroduodenal lobe intact in the same rats.
      This model produced damaged pancreatic tissue in one part and normal pancreatic
      tissue in another part of the pancreas in the same animals, biochemically and
      histologically. We evaluated the effect of a new protease inhibitor (ONO-3404) on
      this preliminary model and found this new protease inhibitor demonstrated a
      hypertrophic effect on the damaged pancreatic tissue and the normal pancreatic
      tissue in the same animals. This model is also useful to study pharmaceutic
      treatment for pancreatic insufficiency and to study chemically induced pancreatic
      carcinogenesis in the damaged pancreatic tissue and the normal pancreatic tissue
      in the same animals.

PMID- 9548669
TI  - Pathophysiologic studies of experimental chronic pancreatitis in rats induced by
      injection of zein-oleic acid-linoleic acid solution into the pancreatic duct.
AB  - An experimental model of chronic pancreatitis was induced by a retrograde
      injection of a viscous solution consisting of zein-oleic acid-linoleic acid (0.05
      ml/100 g body weight) into the rat pancreatic duct. Histologic and biochemical
      changes were investigated over a period of 6 months after induction of this
      model. The treated rats gained weight, but pancreatic weight decreased with time.
      Histologically, the widening of acinar lumen and cellular vacuolization occurred
      within 24 h at the parenchyma neighboring the small ducts filled with the
      injected solution. Degenerative parenchyma, interstitial edema, and inflammatory
      cell infiltration were pronounced 1 week later. Thereafter, duct-like tubular
      complex formation progressed, and the exocrine tissue exhibited marked atrophy of
      the gland with irregular fibrosis and fat replacement over a period of 6 months.
      Pancreatic contents of protein, amylase, DNA, and RNA markedly decreased, as did
      pancreatic weight, whereas hydroxyproline content increased. Oral administration
      of camostat did not affect pancreatic weight and contents of enzyme in this
      model. Urinary para-aminobenzoic acid (PABA) excretion in the BT-PABA test
      decreased to 54% at 6 weeks and 22% at 6 months. Although three quarters of
      pancreatic immunoreactive insulin (IRI) content was lost after 6 months, overt
      diabetes did not occur. The results suggest that an obstructive mechanism in the
      small ducts plays an important role in the genesis and development of chronic
      pancreatitis.

PMID- 9548670
TI  - Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters.
AB  - In this article, we introduce our rapid-production model for pancreatic duct
      adenocarcinomas and describe the mechanisms of pancreatic duct carcinogenesis so
      far elucidated in Syrian golden hamsters. It is evident that a series of
      histogenetic steps are involved, leading from hyperplasia through atypical
      hyperplasia to intraductal carcinoma and invasive carcinoma. As DNA alters, K-ras
      mutation appears to be an early event, whereas p53 mutations generally occur in
      the tumor-progression phase. The induced cancer cells may show autocrine growth,
      secreting TGF-alpha and vascular endothelial growth factor (VEGF), and are
      immortalized with a shortened TRF length and increased telomerase activity. The
      rapid-production model of pancreatic duct adenocarcinomas has not only provided a
      major stimulus to understanding induction mechanisms but should also serve as a
      bioassay to facilitate the identification of dietary risk factors and the search
      for appropriate chemopreventive or chemotherapeutic agents or both to help
      control this deadly disease.

PMID- 9548671
TI  - Acute pancreatitis: overview of medical aspects.
AB  - In this article we describe the current status of treatment of acute pancreatitis
      in Japan and the guidelines established for the treatment of severe acute
      pancreatitis. In 1987 the Research Committee for Intractable Diseases of the
      Pancreas of the Ministry of Health and Welfare conducted a nationwide survey on
      acute pancreatitis to determine the prevalence of the disease between 1982 and
      1986 and the treatment modalities used. Based on a detailed assessment of the
      results of the survey, the Committee developed criteria for rating the severity
      of acute pancreatitis and guidelines for the treatment of acute pancreatitis,
      which was revised in 1995. The five points cited as the principal aspects of
      treatment of severe acute pancreatitis in Japan include (a) rating the severity
      of the disease according to the severity rating criteria; (b) differentiating
      between edematous and necrotic pancreatic lesions and performing dynamic CT of
      the pancreas to define the extent of pancreatic necrosis; (c) performing
      ultrasonography to determine whether there are gallstones; (d) in principle, not
      performing surgery except in patients who clearly have early infection or
      complications after the onset; and (e) providing conservative intensive care
      immediately after the onset. In the absence of complications, the treatment of
      acute pancreatitis in Japan is primarily medical. In contrast to other countries,
      however, administration of antiprotease agents has become an important method of
      treating acute pancreatitis in Japan. Special treatment modalities, such as
      peritoneal lavage, blood purification, and continuous arterial infusion of
      protease inhibitor, are being performed in severe acute pancreatitis, in addition
      to intensive care.

PMID- 9548672
TI  - Acute pancreatitis and cytokines: "second attack" by septic complication leads to
      organ failure.
AB  - Acute pancreatitis is accompanied by destruction and digestion of tissues,
      causing hypercytokinemia and hyperreactivity of leukocytes (macrophages and
      neutrophils) and vascular endothelial cells. As one of the biological defense
      mechanisms in this condition, neutrophils infiltrate vital organs such as the
      lung, liver, and digestive organs. When acute pancreatitis is complicated by
      infection, hyperreactive macrophages release a large amount of proinflammatory
      cytokines that activate primed neutrophils, as a "second attack." Utilizing
      proteolytic enzymes and oxidant, neutrophils injure the infiltrated vital organs,
      causing cellular damage and dysfunction of vital organs distant from the
      pancreas. Multiple organ failure in acute pancreatitis with septic complications
      can develop, at least in part, by proinflammatory cytokine release and neutrophil
      activation.

PMID- 9548673
TI  - Surgical aspects and management of acute necrotizing pancreatitis: recent results
      of a cooperative national survey in Japan.
AB  - A cooperative national survey between 1991 and 1994 recently clarified the status
      of acute necrotizing pancreatitis in Japan. The overall mortality rate was 20.8%;
      however, the mortality rate in patients with infection was 33.3%, and the
      mortality rate in patients who underwent surgery was 27.4%. With regard to
      surgical procedures, drainage procedures (mobilization of the pancreatic bed and
      retroperitoneal drainage) were performed most frequently, and one third of the
      patients who underwent drainage procedures needed reoperation. Although
      debridement of the necrotic tissue (necrosectomy or resection of the pancreas)
      was performed in 33.3%, the mortality rate was 35.3%. There was no difference in
      the mortality rate between early and delayed operation. Recently two new
      modalities have been advocated for the management of severe acute pancreatitis in
      Japan. One is continuous regional arterial infusion of protease inhibitor and
      antibiotics, and the other is continuous hemodiafiltration. Further work is
      needed to establish the most effective procedures for the management of acute
      necrotizing pancreatitis and debridement of pancreatic infection.

PMID- 9548674
TI  - Chronic pancreatitis: overview of medical aspects.
AB  - Based primarily on our experience, we review current problems on etiology,
      pathogenesis, classification, diagnosis, and treatment of chronic pancreatitis.
      Much of the confusion and difficulty associated with chronic pancreatitis
      originates from the relative inaccessibility of this organ. A lack of specific
      and sensitive markers that are suitable for the follow-up of a long natural
      course of chronic pancreatitis also hinders our understanding of this disease.
      The resolution of the present imaging tests, even by the latest technology, is
      not good enough to detect early changes of the pancreas. In the past 10 years,
      several subgroups of patients with alcoholic and idiopathic pancreatitis have
      been identified based on the long-term follow-up study. Pain disappeared
      spontaneously in many patients during the course of the disease, but its
      mechanism is still poorly understood. Removal of pancreatic stones and protein
      plugs by chemical, endoscopic, or extracorporeal shock-wave therapy has been
      tried with some success, but their clinical values remain to be established.
      Attempts have been made to understand the etiology and pathogenesis of chronic
      pancreatitis at molecular levels. This approach, together with a prospective
      follow-up of patients, will improve our understanding on chronic pancreatitis.

PMID- 9548675
TI  - Pancreatic dysfunction and treatment options.
AB  - Pancreatic steatorrhea and pancreatic diabetes are the dominant symptoms of
      patients in the decompensated stage of chronic pancreatitis (CP). In this stage,
      the nutritional state is greatly disturbed and hypoglycemia and labile infection
      are involved. Pancreatic enzyme replacement therapy is the principal treatment
      method for pancreatic steatorrhea. Before initiating this therapy, dietary fat
      intake must be determined and pancreatic lipase and bicarbonate secretion
      function must be evaluated. Upper small intestinal pH is regulated by gastric
      acid secretion, and abnormal gastric emptying changes lipolysis. In addition,
      precipitation of bile acids in the upper small intestine and ileal brakes due to
      undigested fats and carbohydrates must be considered. Porcine pancreatin,
      bacterial lipase, and acid-resistant fungal lipase are used as enzymes for
      replacement therapy. Conventional, entero-coating, and enteric-coated microsphere
      preparations of porcine pancreatin are available for treatment and are formulated
      to protect against gastric acids, to dissolve enzymes at optimum pH, and to be
      emptied simultaneously with food from the stomach. Gastric acid secretion
      suppressants, such as H2 blockers or a proton pump inhibitor, can also be used
      concomitantly with pancreatin preparations. In consideration of both strengths
      and weaknesses of these preparations, types and dosages of enzyme replacement
      therapy should be carefully prescribed, and fecal fats should be examined
      repeatedly by a simple and rapid method during treatment. Attention should also
      be paid to changes in body weight and nutritional indices (e.g., nutritional
      parameters, fat-soluble vitamins). The relationship between carbohydrate
      maldigestion/malabsorption in CP patients and treatment of pancreatic diabetes
      are topics for future research.

PMID- 9548676
TI  - Current surgical trends in Japan for managing chronic pancreatitis.
AB  - The main aims of surgery for treating chronic pancreatitis are to relieve the
      patient's persistent pain and to preserve pancreatic functioning. The indications
      for surgery include treating complications, such as the presence of pancreatic
      pseudocysts or biliary stenosis associated with chronic pancreatitis or both. A
      resection, ductal drainage, or both, may commonly be required. Furthermore, some
      surgeons recommend pancreatic denervation. We analyze the details of 2,936
      patients with chronic pancreatitis who were treated surgically and were listed in
      the 1985 National Statistics in Japan. We have also evaluated the present
      surgical methods for treating chronic pancreatitis in Japan. In addition, we
      discuss a new surgical method being used to treat chronic pancreatitis. This is a
      recently improved technique involving a complete duodenum-preserving resection of
      the head of the pancreas, which also preserves the biliary and alimentary tracts.

PMID- 9548677
TI  - Chronic pancreatitis: functional testing.
AB  - This article reviews the evolution of functional testing of the pancreas in Japan
      for the diagnosis and treatment of chronic pancreatitis (CP), contrasting the pre
      with the postsecretin test (S test) era. In the pre-S test era, the diagnosis
      was based on symptoms, clinical findings, fasting serum diastase levels, and the
      vagostigmin- and ether-stimulation test unless morphologic evidence was
      available. The S test and CCK-pancreozymin (PZ) test (PS test) were introduced
      into Japan around 1963 and have been used as the gold standard of the exocrine
      pancreatic-function test. Through a series of attempts at standardization in
      1971, 1985, and 1987, the method was standardized to collect duodenal juice for
      60 min through a double- or triple-lumen tube after a bolus or during a
      continuous i.v. injection of secretin (100 U). The S test, however, is an
      invasive and cumbersome procedure. As a result, N-benzoyl-L-tyrosal-p
      aminobenzoic acid (BT-PABA) testing and fecal chymotrypsin testing were
      introduced into Japan in the middle and late 1970s, respectively. Although simple
      and noninvasive, these two methods were found have lower sensitivity and
      specificity than the conventional S test. These two methods, therefore, are
      presently used more often for monitoring the course of disease and therapeutic
      effects. Additionally, the glucose tolerance test can be performed to detect
      endocrine pancreatic insufficiency.

PMID- 9548678
TI  - Pancreatic cancer: medical aspects.
AB  - Although pancreatic cancer (PC) continues to be a formidable disease, numerous
      treatment strategies are evolving that we hope will result in improved patient
      survival. To prolong the survival of patients with PC, it is essential to detect
      PC at the earliest stage possible and to develop effective nonsurgical treatments
      for this disease. The current strategies for the early diagnosis of PC include
      the development of diagnostic modalities and screening programs for the early
      detection of PC and the determination of high-risk groups for PC. K-ras mutations
      in pancreatic juice obtained endoscopically have been studied recently in
      association with the early diagnosis of PC, although the interpretation of the
      presence of a mutated K-ras gene requires caution. The role of the current
      nonsurgical treatments for PC has been limited. Identification of an effective
      new chemotherapeutic agent is a high priority, and the enrollment of patients
      with PC with metastatic disease into well-designed clinical trials is essential.
      New targets for therapy based on the understanding of the molecular biology of PC
      may provide avenues for future trials. We must continue to search actively for
      more accurate methods of diagnosis and more effective methods of treatment for
      PC.

PMID- 9548679
TI  - Staging and extended resection for pancreatic cancer.
AB  - Extended surgery is being widely performed to treat pancreatic cancer in Japan,
      but it has not been evaluated in the same way as in other countries. We,
      therefore, compared the Japanese Stage Classification (JPN-SC) with the Union
      Internationale Contre le Cancer Stage Classification (UICC-SC) in the surgical
      cases of pancreatic cancer treated in our department and then assessed the
      results of extended resection and associated problems. Problems existed in the
      resection rates and actuarial survival rates in stages II and III in the UICC-SC,
      and the JPN-SC was found to reflect more accurately the outcome. On the other
      hand, although improvements in curative resection and actuarial survival rate
      have been achieved as a result of extended resection in Japan, the outcome in JPN
      SC surgical stage IVb and highly advanced cases in which these resections proved
      to be noncurative even though they were classified as surgical stage IVa was
      extremely poor. In the future, it will be necessary to decide on a single-stage
      classification that is accepted throughout the world and to conduct prospective
      studies matched to the degree of tumor progression.

PMID- 9548680
TI  - Problems in the diagnosis and treatment of a so-called mucin-producing tumor of
      the pancreas.
AB  - Reports of a so-called "mucin-producing tumor of the pancreas" are increasing
      worldwide. Although the clinicopathologic features and therapeutic strategies of
      this tumor have been enthusiastically investigated, there are still many
      unanswered questions regarding this ailment. In this study, problems in the
      diagnosis and treatment of mucin-producing tumor were analyzed, based on the 259
      reported cases of this tumor. The overall 5-year survival rate for resected cases
      is 83%, which is much higher than that for ordinary duct cell carcinoma (17.3%).
      However, the 5-year survival rate for carcinoma cases with infiltration into
      other organs is 28%, which is much lower than those for carcinoma cases without
      infiltration (86%) and carcinoma cases with infiltration that remained within the
      pancreatic parenchyma (74%). These results demonstrate that patients with this
      tumor have a poor prognosis if the tumor infiltrates other organs. In addition,
      when the spread of the tumor is >6 cm, the prognosis is significantly worse than
      when the tumor has a spread of <6 cm. The significance of using the presence of K
      ras mutation in the pancreatic juice for diagnosis of this tumor and problems of
      duodenum-preserving pancreatic head resection are discussed.

PMID- 9548681
TI  - Surgical aspect of enteroinsular axis after gastrointestinal surgery with
      reference to incretin secretion.
AB  - An alteration of the enteroinsular axis (EIA) may be an important etiologic
      factor in postsurgical changes in gastrointestinal (GI) function. In this review,
      we present recent works, both from our laboratory and others, on how changes in
      the EIA function may be involved in postsurgical GI complications, especially
      late dumping syndrome (LDS). We found no or minimal direct role for vagal signals
      in the control of gastric inhibitory polypeptide (GIP) and enteroglucagon
      secretion, which regulate EIA function. In gastrectomized patients, it is
      suggested that the hypersecretion of glicentin and glucagon-like peptide-1 (GLP
      1) induced by a rapid arrival of nutrients to the distal gut suppresses glucagon
      secretion and may be a cause of LDS. In patients who underwent proctocolectomy,
      we observed no significant postoperative changes in EIA function, although there
      are some conflicting reports. It seems unlikely that ordinary pancreaticobiliary
      diversion would cause a significant change in EIA function after an oral glucose
      load. Our experimental model of ileojejunal transposition produced marked
      hypersecretion of incretin secreted from the distal gut, which may alter EIA
      function. Further elucidation of the regulatory mechanism of EIA may provide a
      new strategy for the medical and surgical treatment of LDS.

PMID- 9548682
TI  - Progress in the field of pancreatic endocrine tumors in Japan.
AB  - Since the first report of pancreatic endocrine tumors by Wilder et al. in 1927
      and the development of radioimmunoassay of gut hormone by Berson and Yallow in
      1961, Japanese clinicians and scientists have contributed significantly in the
      reporting, investigation, and management of patients with pancreatic endocrine
      tumors and other multiple endocrine neoplasia. This article summarizes our
      contribution in this field and contrasts our experiences with those reported in
      the English literature.

PMID- 9548683
TI  - Pancreatic diabetes in Japan.
AB  - Pancreatic diabetes is usually a complication of other pancreatic disorders.
      Diabetes was a complication in 55.5% of 2,774 patients with chronic pancreatitis
      (CP) in Japan. More than half of alcoholic patients with CP in our clinic showed
      diabetes, and approximately 50% of those patients with diabetes were treated with
      insulin injections. On the other hand, cases of nonalcoholic CP showed mild
      endocrine dysfunction in terms of diabetic frequency and severity. Epidemiologic
      studies suggest that diabetes resulting from chronic pancreatitis accounts for
      <0.8% of all Japanese patients with diabetes. In patients with CP, B-cell
      dysfunction occurred first, followed by disturbances in A-cell function.
      Decreased insulin secretion during postprandial periods plays an important role
      in pancreatic diabetes. The fasting level of blood glucose is not useful for the
      diagnosis of the early stage of pancreatic diabetes. The glucose-tolerance test
      should be performed to diagnose early-stage diabetes in patients with CP with
      normal fasting blood glucose levels. For control of blood glucose in diabetic
      patients with CP, multiple injections of short-acting effective insulin before
      the meal are necessary. The incidence of long-term diabetic complications,
      diabetic retinopathy, nephropathy and neuropathy, in patients with CP with
      diabetes are not less than those in patients with primary diabetes.

PMID- 9548684
TI  - Preservation of pancreatic islets in rodent models.
AB  - Islet-cell transplantation has some advantages over vascularized pancreas
      transplantation, but data from clinical islet cells transplantation have shown
      that some serious problems need to be overcome. One of them is the storage of
      islet cells. We investigated methods of preserving islet cells using culture
      preservation and cryopreservation. Cryopreservation is thought to be effective
      for long-term preservation of large quantities of islet cells, because they can
      be cryopreserved without loss of their physiologic activity using a relatively
      rapid cooling rate of 25 degrees C/min. Moreover, in the allogenic
      transplantation models of cryopreservation of dissociated islet cells, there was
      a significant prolongation of survival time. These results suggest that
      cryopreservation of islet cells involves not only variable preservation methods
      but may also lead to a modification of graft immunogenicity.

PMID- 9548685
TI  - Imaging of small pancreatic ductal adenocarcinoma.
AB  - Symptoms and laboratory studies provide only limited assistance in the diagnosis
      of small pancreatic carcinomas. Ultrasound and computed tomography are best
      suited for screening small pancreatic carcinomas because of their ease and
      accuracy. When findings of ultrasound and computed tomography suggest small
      pancreatic carcinomas, MR cholangiopancreatography and endoscopic ultrasound
      should be indicated. Both techniques can show very small tumors. Follow-up of 77
      patients with pancreatic carcinoma in whom the tumor was resected showed a 100% 5
      year survival rate of patients with tumor limited to the duct epithelium. The
      majority of these tumors were <1 cm. These tumors are considered early pancreatic
      carcinoma.

PMID- 9548686
TI  - ERCP imaging.
AB  - Localization and spread of pancreatic diseases has been a reality since the
      availability of endoscopic pancreatography in the late 1960s, particularly after
      development of a fiberscope for this purpose. Endoscopic pancreatography allowed
      the clinician to discern the position and site of cancers, cysts, and localized
      inflammations. Ductal anomalies, such as annular pancreas, nonfusion, and
      anomalous junction of pancreatobiliary connection, were clearly recognized also.
      The pancreatography opacified the real lumen instead of the virtual images of
      ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI),
      so that precise studies comparing histopathologic details could be performed. The
      pancreatic ductal information visualized by using the fiberscope changed our
      understanding of chronic inflammation of the pancreas. Chronic diffuse
      pancreatitis, upstream pancreatitis, ductitis, and duct-narrowing pancreatitis
      were specified from their pathogenetic differences. Although the noninvasive
      methods such as US and CT will be the first choice for the diagnosis of
      pancreatic diseases, pancreatography will still be important for the morphologic
      studies of the pancreas in various disease conditions.

PMID- 9548687
TI  - Peroral pancreatoscopy for the diagnosis of pancreatic diseases.
AB  - The efficacy associated with peroral pancreatoscopy to diagnose and differentiate
      pancreatic diseases is herein reviewed and clarified, and problems with this
      modality are discussed. Three types of pancreatoscopes are presently available:
      (a) a thin fiberscope with a diameter of 3.3 or 4.5 mm, which has an angulation
      system and a forceps channel; (b) an ultrathin pancreatoscope with a diameter of
      0.75 or 0.8 mm, which can be inserted via an ordinary endoscopic retrograde
      cholangiopancreatography (ERCP) cannula without endoscopic sphincterotomy; and
      (c) an ultrathin pancreatoscope combined with a catheter that has an outer
      diameter of 1.67 mm. Peroral pancreatoscopy facilitates the detection of small
      lesions of the duct in malignancy or chronic pancreatitis. In particular, it is
      quite useful in differentiating pancreatic cancer from chronic pancreatitis in
      cases with local stenosis or elevated lesions of the main pancreatic duct. Among
      patients with a mucus-producing tumor of the pancreas, pancreatoscopy is also
      very useful, especially in determining lesion extent. Despite some unresolved
      problems, we predict that pancreatoscopy will retain a limited or specific and
      definite role in diagnostic and therapeutic endoscopy for pancreatic diseases.

PMID- 9548688
TI  - Endoscopic MRI.
AB  - We used a new magnetic resonance endoscope with a small radiofrequent (RF) coil
      attached to the tip. After insertion of the instrument into the second portion of
      the duodenum, patients were placed in a magnetic resonance imaging (MRI) scanner.
      Fast spoiled gradient-recalled acquisition (SPGR) pulse sequences were used for
      this method. After plain scans, six axial scans were performed after intravenous
      injection of 20 ml of gadolinium-diethylenetriaminepentaacetic acid (DTPA)
      contrast medium. We performed endo-MRI on 22 patients, 13 with pancreatic
      carcinoma, four with pancreatic cystoadenoma, and five with other diseases. In
      the patients with pancreatic carcinoma, tumors were delineated as low-intensity
      masses after injection of contrast medium. Dilated main pancreatic ducts were
      clearly defined. In eight patients with carcinoma of the head of the pancreas,
      tumors were clearly defined in seven (87.5%) cases. In the eighth case, motion
      artifact prevented acquisition of a clear image of the pancreas. For diagnosis of
      invasion of the portal vein, the sensitivity of endo-MRI was 80%, the specificity
      was 100%, and overall accuracy was 87.5%. The new technique of endo-MRI allows
      the precise diagnosis of pancreatic tumors.

PMID- 9548689
TI  - Pancreatic diseases: evaluation with MR cholangiopancreatography.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive diagnostic
      modality capable of producing high-quality images of the biliary tree and
      pancreatic duct. We evaluated the MRCP capability of depicting the normal
      pancreatic duct and, based on data achieved, studied the usefulness in the
      pathologic pancreatic duct. MRCP was performed in 42 patients without any
      pancreatic lesion and in 162 patients with pancreatic diseases, including
      congenital anomalies of biliary tree and pancreatic duct. Results were compared
      with endoscopic retrograde cholangiopancreatography (ERCP) in 93 patients. The
      visualization of the pancreatic duct and its branches and the presence or absence
      of dilatation, stenosis, and filling defects were recorded. All images were
      interpreted retrospectively and blindly by three radiologists. Among control
      patients, the main pancreatic duct (MPD) was depicted in the head, body, and tail
      of the pancreas in 41 (98%), 39 (93%), and 31 (74%), and accessory pancreatic
      duct and secondary branches in the head, body, and tail of the pancreas were
      depicted in 11 (26%), eight (19%), four (10%), and two (5%) of these patients.
      Compared with ERCP, MRCP overestimated the stenosis of MPD and underestimated the
      dilatation of the branches and filling defects in the pancreatic duct in
      pancreatic diseases, especially pancreatitis. However, MRCP was distinctly
      advantageous over ERCP in diagnosing mucin-producing tumor of the pancreas,
      cystic lesions, and depicting the whole, including the part distal to the
      obstructed site. Four of the eight cases of pancreas divisum, and 10 of the 12
      cases of anomalous pancreaticobiliary duct union also were demonstrated. MRCP can
      accurately demonstrate the normal pancreatic duct as well as various pancreatic
      duct abnormalities, including congenital anomalies of the biliary tree and
      pancreatic duct.

PMID- 9548690
TI  - Pharmaceutical development for treating pancreatic diseases.
AB  - The efficacy of medications to treat pancreatic diseases, even when proven
      effective by experimental studies, are difficult to prove by controlled clinical
      trials. In the treatment of acute pancreatitis, prophylactic antibiotics,
      somatostatin, protease inhibitors, and cholecystokinin (CCK)-receptor antagonists
      are advocated for use in the early stages of acute pancreatitis, but the data are
      insufficient to mandate prophylaxis use or recommend their use as a standard of
      care. In the treatment of chronic pancreatitis, digestive enzymes, oral active
      protease inhibitors, CCK-receptor antagonists, or somatostatin are administered
      for pain relief. Extracorporeal shock-wave lithotripsy and oral dissolution
      therapy with trimethadione are used to treat pancreatic stones. The goals of
      treatment of acute pancreatitis should be to ameliorate the severity of
      pancreatic inflammation or to prevent its complications. Although several
      treatments seem to be promising from the studies reviewed, these medications
      require prospective comparison with the standard procedures and long-term
      evaluation.

PMID- 9548692
TI  - Japan Pancreas Society research directory, 1998.

PMID- 9548691
TI  - Brief history of the Japan Pancreas Society.

PMID- 9548693
TI  - Deafferentation is insufficient to induce sprouting of A-fibre central terminals
      in the rat dorsal horn.
AB  - The mechanism by which A-fibres sprout into lamina II of the dorsal horn of the
      adult rat after peripheral nerve injury, a region which normally receives input
      from noci- and thermoreceptive C-fibres alone, is not known. Recent findings
      indicating that selective C-fibre injury and subsequent degenerative changes in
      this region are sufficient to induce sprouting of uninjured A-fibres have raised
      the possibility that the structural reorganisation of A-fibre terminals is an
      example of collateral sprouting, in that deafferentation of C-fibre terminals
      alone in lamina II may be sufficient to cause A-fibre sprouting. Primary
      afferents of the sciatic nerve have their cell bodies located predominantly in
      the L4 and L5 dorsal root ganglia (DRGs), and the A-fibres of each DRG have
      central termination fields that show an extensive rostrocaudal overlap in lamina
      III in the L4 and L5 spinal segments. In this study, we have found that C-fibres
      from either DRG have central terminal fields that overlap much less in lamina II
      than A-fibres in lamina III. We have exploited this differential terminal
      organisation to produce deafferentation in lamina II of the L5 spinal segment, by
      an L5 rhizotomy, and then test whether A-fibres of the intact L4 dorsal root
      ganglion, which terminate within the L5 segment, sprout into the denervated
      lamina II in the L5 spinal segment. Neither intact nor peripherally injured A
      fibres were seen to sprout into denervated lamina II after L5 rhizotomy.
      Sprouting was only ever seen into regions of lamina II containing the terminals
      of peripherally injured C-fibres. Therefore, it seems that the creation of
      synaptic space within lamina II is not the explanation for A-fibre sprouting
      after peripheral nerve section or crush, emphasising that injury-induced changes
      in C-fibres and subsequent chemotrophic effects in the superficial dorsal horn
      are the likely explanation.

PMID- 9548695
TI  - Effects of monoamine oxidase A inhibition on barrel formation in the mouse
      somatosensory cortex: determination of a sensitive developmental period.
AB  - Genetic inactivation of monoamine oxidase A (MAOA) in C3H/HeJ mice causes a
      complete absence of barrels in the somatosensory cortex, and similar alterations
      are caused by pharmacological inhibition of MAOA in wild type mice. To determine
      when and how MAOA inhibition affects the development of the barrel field, the
      MAOA inhibitor clorgyline was administered to mice of the outbred strain OF1 for
      various time periods between embryonic day 15 (E15) and postnatal day 7 (P7), and
      the barrel fields were analyzed with cytochrome oxidase and Nissl stains in P10
      and adult mice. High-pressure liquid chromatography measures of brain serotonin
      (5-HT) showed three- to eightfold increases during the periods of clorgyline
      administration. Perinatal mortality was increased and weight gain was slowed
      between P3 and P6. Clorgyline treatments from E15 to P7 or from P0 to P7
      disrupted the formation of barrels in the anterior snout representation and in
      parts of the posteromedial barrel subfield (PMBSF). Treatments from P0 to P4
      caused similar although less severe barrel field alterations. Clorgyline
      treatments only during embryonic life or starting on P4 caused no detectable
      abnormalities. In cases with barrel field alterations, a rostral-to-caudal
      gradient of changes was noted: Rostral barrels of the PMBSF were most frequently
      fused and displayed an increased size tangentially. Thus, MAOA inhibition
      resulting in increased brain levels of 5-HT affects barrel development during the
      entire first postnatal week, with a sensitive period between P0 and P4. The
      rostral-to-caudal gradient of changes in the barrel field parallels known
      developmental gradients in the sensory periphery and in the maturation
      thalamocortical afferents. The observed barrel fusions could correspond to a
      default in the initial segregation of thalamic fibers or to a continued,
      exuberant growth of these fibers that overrides the tangential domain that is
      normally devoted to individual whiskers.

PMID- 9548694
TI  - Methionine enkephalin immunoreactivity in the brain of the budgerigar
      (Melopsittacus undulatus): similarities and differences with respect to oscine
      songbirds.
AB  - The brain of the budgerigar (Melopsittacus undulatus), a small parrot that
      acquires new vocalizations throughout life, was examined for immunoreactivity to
      the opioid peptide methionine enkephalin (mENK). mENK is a highly prominent
      feature of the chemical architecture of the forebrain vocal system of oscine
      songbirds. Forebrain vocal control nuclei are believed to have evolved
      independently in parrots and songbirds (Streidter [1994] J. Comp. Neurol. 343:35
      56); however, recent studies have found similarities in the neural organization
      of vocal control pathways in budgerigars and songbirds (Durand et al. [1997] J.
      Comp. Neurol. 377:179-206). Among the similarities are the existence of recursive
      pathways interconnecting vocal control neurons in the archistriatum, basal
      ganglia (i.e., lobus parolfactorius), and dorsal thalamus. In the present study,
      we found that all vocal control nuclei within the budgerigar forebrain exhibit
      prominent mENK-like immunoreactivity (ELI) in fibers and somata. We also found
      striking similarities between the morphology of ELI elements in budgerigar vocal
      control nuclei and that described previously in songbird vocal nuclei. Despite
      these similarities, the budgerigar dorsal striatopallidum (lobus parolfactorius,
      paleostriatum augmentatum, and paleostriatum primitivum) and somatomotor
      (anterior) archistriatum exhibit unique patterns of ELI. The dorsal
      striatopallidum contained far less ELI, whereas the archistriatum contained far
      more than would be expected on the basis of previous studies of opioid peptides
      in other avian species, including pigeons, chickens, and songbirds. These
      differences may reflect neural specializations unique to the budgerigar that
      contribute to the extraordinary flexibility of the vocal motor system of this
      species to acquire socially significant stimuli throughout life.

PMID- 9548696
TI  - Localization of the origin of retinal efferents in the turtle brain and the
      involvement of nitric oxide synthase.
AB  - Previous studies have used selective neurochemical markers or retrograde tracers
      to localize the cells in the brain giving rise to efferents to the turtle retina.
      Because of the relative selectivity of the neurochemical markers or the lack of
      sensitivity of the previously employed retrograde tracers, these studies did not
      locate all the efferent cell bodies, or they could not describe the anatomy of
      the efferent cells. In the present study, cholera toxin B was used as a highly
      sensitive retrograde tracer to investigate the distribution, number, and
      morphology of the retinal efferent or centrifugal cell system in turtle brain.
      Previous studies of the turtle retina have indicated that nitric oxide synthase
      may be found in some retinal efferents. Therefore, we also did colocalization
      studies of the retrograde tracer with reduced nicotinamide adenine dinucleotide
      phosphate (NADPH)-diaphorase histochemistry to investigate nitric oxide as a
      possible transmitter used by efferent fibers and to localize these NADPH
      diaphorase-positive efferent cell bodies in the turtle brain. We found that each
      eye received projections from approximately 40 efferent cell bodies that were
      located primarily in the contralateral midbrain. The majority of efferent cell
      bodies were centered in the isthmic tegmentum; other efferent cells extended more
      rostrally into the substantia nigra, and some efferent cells extended more
      caudally into the nucleus raphes superior. The double-label results showed that
      30% of the cholera toxin B-like immunoreactive cells were also positive for NADPH
      diaphorase. The location of these double-labeled cells around the locus coeruleus
      corresponded to the NADPH-diaphorase-positive efferent cells in the avian isthmo
      optic field. The localization of NADPH-diaphorase in these efferents indicated
      that they may use nitric oxide to modulate retinal function.

PMID- 9548697
TI  - Horizontal cell connections with short wavelength-sensitive cones in the retina:
      a comparison between New World and Old World primates.
AB  - Recent studies in the Old World macaque monkey have shown that the two horizontal
      cell types H1 and H2 differ with respect to their connections to short wavelength
      sensitive (SWS) cones. We wanted to establish whether this pattern of
      connectivity is common to all primates. The connections of horizontal cells with
      SWS cones were studied in the retinas of two species of New World (marmoset and
      tamarin) and two species of Old World (orangutan and chimpanzee) primates by
      using a double-labelling technique. Horizontal cells were labelled with DiI and
      then photoconverted; SWS cones were labelled immunocytochemically. The marmoset
      shows a sex-linked polymorphism of colour vision: All males are dichromats,
      whereas most females are trichromats. In contrast, Old World primates are usually
      trichromats. Our results show that the horizontal cells of both New World and Old
      World primates have a comparable pattern of connectivity with SWS cones and thus
      indicate that the wiring of horizontal cells with SWS cones does not differ
      between dichromats and trichromats and is common to all primates. The H1 cells
      make no or only sparse contact with SWS cones. In marmoset, H1 cells have on
      average 0.8% of their dendritic terminals at SWS cones. The H2 cells contact all
      SWS cones in their dendritic field. In marmoset, H2 cells have on average 11.8%
      of their dendritic terminals at SWS cones. The axon of H2 cells contacts SWS
      cones but presumably also contacts other cones.

PMID- 9548698
TI  - Spatiotemporal patterns of ontogenetic expression of parvalbumin in the superior
      colliculi of rats and rabbits.
AB  - We have examined the development of parvalbumin immunoreactivity in the superior
      colliculi (SC) of the perinatal and mature rats and rabbits. In mature animals,
      parvalbumin-expressing cells (PECs) and neuropil in the retinorecipient layers
      were distributed in a continuous single band extending throughout the entire
      extent of the colliculus, whereas those in the intermediate layers formed
      distinct, radially oriented patches. Parvalbumin was expressed for the first time
      on postconceptional day 34 (PCD 34, postnatal day 12) and PCD 42 (postnatal day
      11) in the SC of rat and rabbit, respectively. During ensuing development, both
      the thickness of the parvalbumin-expressing band in the retinorecipient layers
      and the numbers of PECs in this band gradually increased, reaching adultlike
      values by PCD 44 and PCD 50 in the rat and rabbit, respectively. In the rat,
      monocular eye enucleations on PCD 23 resulted in approximately 55% reduction in
      the number of PECs in the retinorecipient layers of the contralateral colliculi
      examined on PCD 44 or PCD 50. Unilateral ablations of the entire visual cortex on
      PCD 23 (before the first corticotectal fibers from visual cortices reach the SC)
      or on PCD 28 (when about half of the corticotectal fibers have reached
      colliculus) resulted in, respectively, approximately 55% and approximately 25%
      relative reduction in the number of PECs in the retinorecipient layers of the
      ipsilateral colliculi examined on PCD 44 or PCD 50. We conclude that the
      ontogenetic expression of parvalbumin in most of PECs in the retinorecipient
      collicular layers is induced by the activity of the contralateral retinotectal
      and/or the activity of the ipsilateral corticotectal afferents.

PMID- 9548699
TI  - Overexpression of nerve growth factor in epidermis disrupts the distribution and
      properties of sympathetic innervation in footpads.
AB  - Sympathetic and sensory neurons form distinct axonal arborizations in several
      peripheral targets. The developmental mechanisms responsible for partitioning
      sympathetic and sensory axons between potential target tissues are poorly
      understood. We have used rodent footpads to study this process because three
      populations of peripheral axons innervate topographically segregated targets in
      the footpad; cholinergic sympathetic axons innervate sweat glands, noradrenergic
      sympathetic axons innervate blood vessels, and sensory axons form a plexus at the
      epidermal/dermal junction. To examine how nerve growth factor (NGF), a trophic
      and survival factor for sympathetic and some sensory neurons, may contribute to
      the generation of the patterned distribution of axons among targets, we studied
      transgenic mice (K14-NGF mice) in which NGF expression was significantly
      increased in the epidermis. Whereas the temporal sequence in which sensory and
      sympathetic fibers arrived in the footpad was not affected, the normal
      partitioning of axons between target tissues was disrupted. The two sympathetic
      targets in footpads, sweat glands, and blood vessels lacked substantial
      innervation and instead a dense plexus of catecholaminergic sympathetic fibers
      was found commingled with sensory fibers in the dermis. Those sympathetic fibers
      present in sweat glands expressed an abnormal dual catecholaminergic/cholinergic
      phenotype. Our findings indicate that overexpression of NGF in skin interferes
      with the segregation of sensory and sympathetic axonal arbors and suggests a role
      for target-derived NGF in the establishment of distinct axonal territories. Our
      data also suggest that by determining where axon arbors form, NGF can indirectly
      influence the phenotypic properties of sympathetic neurons.

PMID- 9548700
TI  - Hypothalamic effector neurons and extended circuitries activated in "neurogenic"
      stress: a comparison of footshock effects exerted acutely, chronically, and in
      animals with controlled glucocorticoid levels.
AB  - Immunolocalization of Fos protein was used to identify and characterize
      hypothalamic visceromotor populations responsive to acute and chronic
      intermittent footshock stress, and candidate afferent mediators of hypothalamic
      effects. Exposure to a single 30 minute footshock session induced maximal Fos
      expression in the paraventricular hypothalamic nucleus (PVH) 2 hours after the
      challenge; activated cells corresponded principally to hypophysiotropic neurons
      expressing corticotropin-releasing factor, with secondary involvement of
      magnocellular oxytocinergic and autonomic-related projection neurons.
      Extrahypothalamic cell groups activated in response to acute footshock included
      ones associated with the processing or modulation of somatosensory/nociceptive
      inputs, the limbic region of the telencephalon, and visceral sensory mechanisms.
      Rats with constant corticosterone levels displayed enhanced footshock-induced Fos
      expression in the parvicellular compartment of the PVH, as well as in certain
      limbic and somatosensory cell groups, the locus coeruleus, but not in medullary
      catecholaminergic cell groups. Animals subjected to chronic intermittent stress
      (2 sessions/day for 7 days) showed only modest evidence of habituation of
      cellular activation responses in the PVH and most extrahypothalamic regions. Rats
      bearing retrograde tracer deposits in the PVH and killed 2 hours after acute
      footshock displayed Fos-positive retrogradely labeled neurons principally in
      medullary catecholaminergic cell groups, with secondary foci in the hypothalamus,
      limbic region, and pontine tegmentum. This characterization of footshock
      responsive systems identifies cell groups that are in a position to (1) mediate
      acute stress effects on hypothalamic visceromotor neurons, (2) comprise targets
      for corticosteroid negative feedback effects, and/or (3) underlie habituation of
      the neuroendocrine limb of the stress response.

PMID- 9548701
TI  - Caregiving for children and adults with chronic conditions: introduction to the
      special issue.

PMID- 9548702
TI  - Role strain in couples with and without a child with a chronic illness:
      associations with marital satisfaction, intimacy, and daily mood.
AB  - This study examined marital role strain in 33 couples caring for a child with
      cystic fibrosis (CF) and 33 couples with a healthy child. The relationship
      between role strain, marital satisfaction, and psychological distress was tested.
      Couples completed a structured interview, questionnaires, a card sort procedure,
      and 4 daily diaries assessing activities and mood. Couples in the CF versus
      comparison group reported greater role strain on measures of role conflict, child
      care tasks, and exchanges of affection. They also spent less time in recreational
      activities, but no reliable group differences were found in marital satisfaction
      or depression. Regression analyses indicated that role strain was related to
      marital satisfaction and depression and that recreation time accounted for
      additional variance. Path analysis suggested that recreation mediated the
      negative relationship between role strain and distress. The importance of using a
      contextual, process-oriented approach is discussed.

PMID- 9548703
TI  - Dynamic processes in health outcomes among caregivers of patients with spinal
      cord injuries.
AB  - The developmental trajectories of health outcomes in caregivers of patients with
      spinal cord injuries (SCIs) were studied as a function of caregiver and patient
      characteristics. Hierarchical linear modeling analysis examined (a)
      intraindividual developmental patterns of depressive behavior, anxiety, and
      physical symptoms over the 1st year of the caregiving career and (b) correlates
      of heterogeneity in the developmental patterns among 62 caregivers of persons
      with SCIs. Physical symptoms and anxiety were highly interdependent. Anxiety was
      a salient predictor of initial levels of and the rate of change in physical
      symptoms of caregivers. Physical symptoms and younger patient age were
      significantly predictive of initial levels of anxiety. Physical symptoms and
      positive affect predicted initial levels of depressive behavior among caregivers.
      Expressive support predicted the rate of change in anxiety and depressive
      behavior over time. These findings illustrate the value of studying caregiving as
      a developmental process.

PMID- 9548704
TI  - AIDS caregiving and health among midlife and older women.
AB  - This study reports on analyses of survey data from 121 midlife and older women
      engaged in AIDS caregiving in Los Angeles and San Francisco. These data revealed
      that these women provided substantial support to persons living with HIV or AIDS
      (PWAs) despite other role commitments associated with family and work. Although
      the characteristics of these women differed according to their relationship to
      the PWA (mother, wife, sister, or friend), they tended to be similar with regard
      to both the amount of care provided and its impact on their health. The results
      indicated that the severity of the PWA's illness and the duration of caregiving
      were more consequential to health than were the hands-on tasks of caregiving.

PMID- 9548705
TI  - Temporal profiles of physical health in family members of heart transplant
      recipients: predictors of health change during caregiving.
AB  - This study examined patterns of change in the physical health and well-being of
      133 family caregivers to heart transplant recipients during the 1st year after
      transplant. Caregivers were assessed at 2, 7, and 12 months after transplant.
      Cluster analysis was used to identify temporal profiles reflecting unique
      patterns of change in the direction and nature of caregivers' physical health;
      their temporal profiles showed either (a) a worsening of general medical
      condition, with weight gain (14% of the sample); (b) worsening medical condition
      with weight loss (15%); (c) weight gain with stable medical condition (41%); (d)
      weight loss with slightly improving medical condition (21%); or (e) worsening
      health perceptions with relatively little objective evidence of change in medical
      condition or weight (8%). Subsequent multivariate analyses indicated that
      caregiver characteristics measured at baseline and reflecting caregiving burden,
      coping styles, demographics, and health history reliably predicted membership in
      the pattern-of-health-change groups. Among the findings, caregivers who showed a
      pattern of medical decline with weight loss had a poorer health history and
      weaker coping styles (lower mastery and higher use of avoidance coping) than
      other caregivers. Caregivers who experienced medical decline with weight gain had
      the greatest levels of caregiver burden. These findings are relevant to the
      design of interventions to maximize not only caregivers' health, but the health
      of the family members for whom they provide care.

PMID- 9548706
TI  - Activity restriction and prior relationship history as contributors to mental
      health outcomes among middle-aged and older spousal caregivers.
AB  - In a sample of cancer patients (n = 75) and spousal caregivers (24 men and 51
      women), restriction in caregiver routine activities mediated associations between
      caregiving stress (patient symptom severity) and caregiver depressed affect and
      resentment. Moreover, the antecedents and affective consequences of caregiver
      activity restriction were consistent with the theory of communal relationships
      (e.g., M. S. Clark & J. Mills, 1979, 1993). If a relationship had been communal
      in the past (i.e., characterized by mutual concern for and responsiveness to one
      another's needs), activity restriction was predicted by intimacy and affectional
      loss (rather than by the severity of patient symptoms) and in turn predicted
      caregiver depressed affect. Among caregivers in less communal relationships,
      activity restriction was predicted by severity of patient symptoms (rather than
      by intimacy and affectional loss) and in turn predicted resentment of care
      recipients and the caregiving role.

PMID- 9548707
TI  - Mastery in women's multiple roles and well-being: adult daughters providing care
      to impaired parents.
AB  - The current study focused on 296 adult daughter caregivers who were
      simultaneously providing care to an impaired parent, mothers to children living
      at home, wives, and employees. How mastery (perceived competence and control) in
      each of these 4 roles was related to well-being was examined. Women experienced
      higher levels of mastery in the employee role than in any other role. After
      controlling for household income and dispositional optimism, only employee
      mastery contributed unique variance to physical health, but mastery in each of
      the 4 roles contributed unique variance to either depression or life
      satisfaction. Results also suggest that women's satisfaction with life was
      related to an accumulation of mastery across roles. The study expands previous
      research by revealing that mastery in women's additional roles can supplement the
      benefits of mastery stemming from parent care.

PMID- 9548708
TI  - Caregiving from the recipient's perspective: negative reactions to being helped.
AB  - This study investigated predictors of negative reactions to assistance provided
      to a physically disabled spouse (n = 276, M age: 76.6 years) and the consequences
      that negative reactions may have for the mental health of the care recipient.
      Nearly 40% of recipients reported some emotional distress in response to help
      they received. Fatalistic attitudes, perceived control, and lower self-esteem
      predicted greater helping distress, whereas lower self-esteem, fatalistic
      beliefs, and marital conflict were especially likely to lead to helping distress
      for those who received higher levels of assistance. Helping distress was also
      found to predict depression as much as 1 year later, suggesting that there may be
      long-term consequences of negative reactions to assistance. These findings have
      important implications for the study of caregiving and the relationship between
      physical impairment and depression.

PMID- 9548709
TI  - Cellular immune responses to acute stress in female caregivers of dementia
      patients and matched controls.
AB  - This study investigated whether the stress of caregiving alters cellular immune
      responses to acute psychological stressors. Twenty-seven women caring for a
      spouse with a progressive dementia (high chronic stress) and 37 controls matched
      for age and family income performed a 12-min laboratory stressor. Cellular immune
      function was assessed by both functional and quantitative measures taken before
      (low acute stress), immediately after (high acute stress), and 30 min after
      (recovery from stress) exposure to the laboratory stressors. The laboratory
      challenges were associated with diminished proliferative responses but elevated
      natural killer (NK) cell cytotoxicity; however, subsequent analyses suggested
      that this elevated cytotoxicity was largely attributable to an increase in the
      number of NK cells in peripheral blood. The results suggest that although the
      stress of caregiving diminishes cellular immune function, caregiving appears to
      have little effect on cellular immune responses to or recovery from brief
      psychological challenges.

PMID- 9548710
TI  - Predicting longitudinal changes in caregiver physical and mental health: a stress
      process model.
AB  - Alzheimer's family caregivers (N = 122) reported on physical and mental health,
      as well as stress process variables, at baseline and at a 1-year follow-up.
      Hierarchical regression analyses of stress process models revealed that increases
      in primary stressors (e.g., patient self-care and behavioral problems) did not
      directly affect changes in the mental and physical health outcome variables.
      However, analyses of models of direct, mediated, and moderated effects revealed
      that psychosocial resource variables (appraisals, coping responses, and social
      support) were related to caregiver outcomes over time through several mechanisms.
      In particular, benign appraisals of stressors, the use of approach coping, and
      greater levels of social support were associated with more positive caregiver
      health outcomes over time.

PMID- 9548711
TI  - Centromere protein B null mice are mitotically and meiotically normal but have
      lower body and testis weights.
AB  - CENP-B is a constitutive centromere DNA-binding protein that is conserved in a
      number of mammalian species and in yeast. Despite this conservation, earlier
      cytological and indirect experimental studies have provided conflicting evidence
      concerning the role of this protein in mitosis. The requirement of this protein
      in meiosis has also not previously been described. To resolve these
      uncertainties, we used targeted disruption of the Cenpb gene in mouse to study
      the functional significance of this protein in mitosis and meiosis. Male and
      female Cenpb null mice have normal body weights at birth and at weaning, but
      these subsequently lag behind those of the heterozygous and wild-type animals.
      The weight and sperm content of the testes of Cenpb null mice are also
      significantly decreased. Otherwise, the animals appear developmentally and
      reproductively normal. Cytogenetic fluorescence-activated cell sorting and
      histological analyses of somatic and germline tissues revealed no abnormality.
      These results indicate that Cenpb is not essential for mitosis or meiosis,
      although the observed weight reduction raises the possibility that Cenpb
      deficiency may subtly affect some aspects of centromere assembly and function,
      and result in reduced rate of cell cycle progression, efficiency of microtubule
      capture, and/or chromosome movement. A model for a functional redundancy of this
      protein is presented.

PMID- 9548712
TI  - Human autoantibodies reveal titin as a chromosomal protein.
AB  - Assembly of the higher-order structure of mitotic chromosomes is a prerequisite
      for proper chromosome condensation, segregation and integrity. Understanding the
      details of this process has been limited because very few proteins involved in
      the assembly of chromosome structure have been discovered. Using a human
      autoimmune scleroderma serum that identifies a chromosomal protein in human cells
      and Drosophila embryos, we cloned the corresponding Drosophila gene that encodes
      the homologue of vertebrate titin based on protein size, sequence similarity,
      developmental expression and subcellular localization. Titin is a giant
      sarcomeric protein responsible for the elasticity of striated muscle that may
      also function as a molecular scaffold for myofibrillar assembly. Molecular
      analysis and immunostaining with antibodies to multiple titin epitopes indicates
      that the chromosomal and muscle forms of titin may vary in their NH2 termini. The
      identification of titin as a chromosomal component provides a molecular basis for
      chromosome structure and elasticity.

PMID- 9548713
TI  - The genomic sequences bound to special AT-rich sequence-binding protein 1 (SATB1)
      in vivo in Jurkat T cells are tightly associated with the nuclear matrix at the
      bases of the chromatin loops.
AB  - Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein
      expressed predominantly in thymocytes, recognizes an ATC sequence context that
      consists of a cluster of sequence stretches with well-mixed A's, T's, and C's
      without G's on one strand. Such regions confer a high propensity for stable base
      unpairing. Using an in vivo cross-linking strategy, specialized genomic sequences
      (0.1-1. 1 kbp) that bind to SATB1 in human lymphoblastic cell line Jurkat cells
      were individually isolated and characterized. All in vivo SATB1-binding sequences
      examined contained typical ATC sequence contexts, with some exhibiting homology
      to autonomously replicating sequences from the yeast Saccharomyces cerevisiae
      that function as replication origins in yeast cells. In addition, LINE 1
      elements, satellite 2 sequences, and CpG island-containing DNA were identified.
      To examine the higher-order packaging of these in vivo SATB1-binding sequences,
      high-resolution in situ fluorescence hybridization was performed with both
      nuclear "halos" with distended loops and the nuclear matrix after the majority of
      DNA had been removed by nuclease digestion. In vivo SATB1-binding sequences
      hybridized to genomic DNA as single spots within the residual nucleus
      circumscribed by the halo of DNA and remained as single spots in the nuclear
      matrix, indicating that these sequences are localized at the base of chromatin
      loops. In human breast cancer SK-BR-3 cells that do not express SATB1, at least
      one such sequence was found not anchored onto the nuclear matrix. These findings
      provide the first evidence that a cell type-specific factor such as SATB1 binds
      to the base of chromatin loops in vivo and suggests that a specific chromatin
      loop domain structure is involved in T cell-specific gene regulation.

PMID- 9548714
TI  - Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its
      ubiquitination and internalization.
AB  - G protein-coupled (GPC) receptors are phosphorylated in response to ligand
      binding, a modification that promotes receptor desensitization or downregulation.
      The alpha-factor pheromone receptor (Ste2p) of Saccharomyces cerevisiae is a GPC
      receptor that is hyperphosphorylated and ubiquitinated upon binding alpha-factor.
      Ubiquitination triggers Ste2p internalization into the endocytic pathway. Here we
      demonstrate that phosphorylation of Ste2p promotes downregulation by positively
      regulating ubiquitination and internalization. Serines and a lysine are essential
      elements of the Ste2p SINNDAKSS internalization signal that can mediate both
      constitutive and ligand-stimulated endocytosis. The SINNDAKSS serines are
      required for receptor phosphorylation which, in turn, facilitates ubiquitination
      of the neighboring lysine. Constitutive phosphorylation is required to promote
      constitutive internalization, and is also a prerequisite for ligand-induced
      phosphorylation at or near the SINNDAKSS sequence. Mutants defective in yeast
      casein kinase I homologues are unable to internalize alpha-factor, and do not
      phosphorylate or ubiquitinate the receptor, indicating that these kinases play a
      direct or indirect role in phosphorylating the receptor. Finally, we provide
      evidence that the primary function of phosphorylation controlled by the SINNDAKSS
      sequence is to trigger receptor internalization, demonstrating that
      phosphorylation-dependent endocytosis is an important mechanism for the
      downregulation of GPC receptor activity.

PMID- 9548715
TI  - Mannose 6-phosphate receptors are sorted from immature secretory granules via
      adaptor protein AP-1, clathrin, and syntaxin 6-positive vesicles.
AB  - The occurrence of clathrin-coated buds on immature granules (IGs) of the
      regulated secretory pathway suggests that specific transmembrane proteins are
      sorted into these buds through interaction with cytosolic adaptor proteins. By
      quantitative immunoelectron microscopy of rat endocrine pancreatic beta cells and
      exocrine parotid and pancreatic cells, we show for the first time that the
      mannose 6-phosphate receptors (MPRs) for lysosomal enzyme sorting colocalize with
      the AP-1 adaptor in clathrin-coated buds on IGs. Furthermore, the concentrations
      of both MPR and AP-1 decline by approximately 90% as the granules mature.
      Concomitantly, in exocrine secretory cells lysosomal proenzymes enter and then
      are sorted out of IGs, just as was previously observed in beta cells (Kuliawat,
      R., J. Klumperman, T. Ludwig, and P. Arvan. 1997. J. Cell Biol. 137:595-608). The
      exit of MPRs in AP-1/clathrin-coated buds is selective, indicated by the fact
      that the membrane protein phogrin is not removed from maturing granules. We have
      also made the first observation of a soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor, syntaxin 6, which has been implicated in clathrin
      coated vesicle trafficking from the TGN to endosomes (Bock, J.B., J. Klumperman,
      S. Davanger, and R.H. Scheller. 1997. Mol. Biol. Cell. 8:1261-1271) that enters
      and then exits the regulated secretory pathway during granule maturation. Thus,
      we hypothesize that during secretory granule maturation, MPR-ligand complexes and
      syntaxin 6 are removed from IGs by AP-1/clathrin-coated vesicles, and then
      delivered to endosomes.

PMID- 9548716
TI  - Peroxisome biogenesis: involvement of ARF and coatomer.
AB  - Peroxisomal membrane protein (Pmp)26p (RnPex11p), a major constituent of induced
      rat liver peroxisomal membrane, was found to contain a COOH-terminal,
      cytoplasmically exposed consensus dilysine motif with the potential to bind
      coatomer. Biochemical as well as immunocytochemical evidence is presented showing
      that peroxisomes incubated with preparations of bovine brain or rat liver cytosol
      recruit ADP-ribosylation factor (ARF) and coatomer in a strictly guanosine 5'-O
      (3-thiotriphosphate)-dependent manner. Consistent with this observation, ldlF
      cells expressing a temperature-sensitive mutant version of the epsilon-subunit of
      coatomer exhibit elongated tubular peroxisomes possibly due to impaired
      vesiculation at the nonpermissive temperature. Since overexpression of Pex11p in
      Chinese hamster ovary wild-type cells causes proliferation of peroxisomes, these
      data suggest that Pex11p plays an important role in peroxisome biogenesis by
      supporting ARF- and coatomer-dependent vesiculation of the organelles.

PMID- 9548717
TI  - A SecY homologue is required for the elaboration of the chloroplast thylakoid
      membrane and for normal chloroplast gene expression.
AB  - Results of in vitro and genetic studies have provided evidence for four pathways
      by which proteins are targeted to the chloroplast thylakoid membrane. Although
      these pathways are initially engaged by distinct substrates and involve some
      distinct components, an unresolved issue has been whether multiple pathways
      converge on a common translocation pore in the membrane. A homologue of
      eubacterial SecY called cpSecY is localized to the thylakoid membrane. Since SecY
      is a component of a protein-translocating pore in bacteria, cpSecY likely plays
      an analogous role. To explore the role of cpSecY, we obtained maize mutants with
      transposon insertions in the corresponding gene. Null cpSecY mutants exhibit a
      severe loss of thylakoid membrane, differing in this regard from mutants lacking
      cpSecA. Therefore, cpSecY function is not limited to a translocation step
      downstream of cpSecA. The phenotype of cpSecY mutants is also much more
      pleiotropic than that of double mutants in which both the cpSecA- and DeltapH
      dependent thylakoid-targeting pathways are disrupted. Therefore, cpSecY function
      is likely to extend beyond any role it might play in these targeting pathways.
      CpSecY mutants also exhibit a defect in chloroplast translation, revealing a link
      between chloroplast membrane biogenesis and chloroplast gene expression.

PMID- 9548718
TI  - Occludin-deficient embryonic stem cells can differentiate into polarized
      epithelial cells bearing tight junctions.
AB  - Occludin is the only known integral membrane protein of tight junctions (TJs),
      and is now believed to be directly involved in the barrier and fence functions of
      TJs. Occludin-deficient embryonic stem (ES) cells were generated by targeted
      disruption of both alleles of the occludin gene. When these cells were subjected
      to suspension culture, they aggregated to form simple, and then cystic embryoid
      bodies (EBs) with the same time course as EB formation from wild-type ES cells.
      Immunofluorescence microscopy and ultrathin section electron microscopy revealed
      that polarized epithelial (visceral endoderm-like) cells were differentiated to
      delineate EBs not only from wild-type but also from occludin-deficient ES cells.
      Freeze fracture analyses indicated no significant differences in number or
      morphology of TJ strands between wild-type and occludin-deficient epithelial
      cells. Furthermore, zonula occludens (ZO)-1, a TJ-associated peripheral membrane
      protein, was still exclusively concentrated at TJ in occludin-deficient
      epithelial cells. In good agreement with these morphological observations, TJ in
      occludin-deficient epithelial cells functioned as a primary barrier to the
      diffusion of a low molecular mass tracer through the paracellular pathway. These
      findings indicate that there are as yet unidentified TJ integral membrane
      protein(s) which can form strand structures, recruit ZO-1, and function as a
      barrier without occludin.

PMID- 9548719
TI  - Association of the myosin-binding subunit of myosin phosphatase and moesin: dual
      regulation of moesin phosphorylation by Rho-associated kinase and myosin
      phosphatase.
AB  - The small GTPase Rho is believed to regulate the actin cytoskeleton and cell
      adhesion through its specific targets. We previously identified the Rho targets:
      protein kinase N, Rho-associated kinase (Rho-kinase), and the myosin-binding
      subunit (MBS) of myosin phosphatase. We found that in MDCK epithelial cells, MBS
      accumulated at the tetradecanoylphorbol-13-acetate (TPA)-induced membrane
      ruffling area, where moesin, a member of the ERM (ezrin, radixin, and moesin)
      family, was localized. Neither membrane ruffling nor an accumulation of moesin
      and MBS at the free-end plasma membrane was induced when MDCK cells were
      stimulated with TPA after the microinjection of C3, which ADP-ribosylates and
      inactivates Rho. MBS was colocalized with moesin at the cell-cell contact sites
      in MDCK cells. We also found that moesin was coimmunoprecipitated with MBS from
      MDCK cells. Recombinant MBS interacted with the amino-terminal domains of moesin
      and ezrin. Myosin phosphatase composed of the catalytic subunit and MBS showed
      phosphatase activity toward moesin, which was phosphorylated by Rho-kinase. The
      phosphatase activity was inhibited when MBS was phosphorylated by Rho-kinase.
      These results suggest that MBS is recruited with moesin to the plasma membrane
      and that myosin phosphatase and Rho-kinase regulate the phosphorylation state of
      moesin downstream of Rho.

PMID- 9548720
TI  - Image reconstructions of microtubules decorated with monomeric and dimeric
      kinesins: comparison with x-ray structure and implications for motility.
AB  - We have decorated microtubules with monomeric and dimeric kinesin constructs,
      studied their structure by cryoelectron microscopy and three-dimensional image
      reconstruction, and compared the results with the x-ray crystal structure of
      monomeric and dimeric kinesin. A monomeric kinesin construct (rK354, containing
      only a short neck helix insufficient for coiled-coil formation) decorates
      microtubules with a stoichiometry of one kinesin head per tubulin subunit (alpha
      beta-heterodimer). The orientation of the kinesin head (an anterograde motor) on
      the microtubule surface is similar to that of ncd (a retrograde motor). A longer
      kinesin construct (rK379) forms a dimer because of the longer neck helix forming
      a coiled-coil. Unexpectedly, this construct also decorates the microtubule with a
      stoichiometry of one head per tubulin subunit, and the orientation is similar to
      that of the monomeric construct. This means that the interaction with
      microtubules causes the two heads of a kinesin dimer to separate sufficiently so
      that they can bind to two different tubulin subunits. This result is in contrast
      to recent models and can be explained by assuming that the tubulin-kinesin
      interaction is antagonistic to the coiled-coil interaction within a kinesin
      dimer.

PMID- 9548721
TI  - Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A
      motor protein-deficient mice.
AB  - The nerve axon is a good model system for studying the molecular mechanism of
      organelle transport in cells. Recently, the new kinesin superfamily proteins
      (KIFs) have been identified as candidate motor proteins involved in organelle
      transport. Among them KIF1A, a murine homologue of unc-104 gene of Caenorhabditis
      elegans, is a unique monomeric neuron- specific microtubule plus end-directed
      motor and has been proposed as a transporter of synaptic vesicle precursors
      (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa. 1995. Cell. 81:769
      780). To elucidate the function of KIF1A in vivo, we disrupted the KIF1A gene in
      mice. KIF1A mutants died mostly within a day after birth showing motor and
      sensory disturbances. In the nervous systems of these mutants, the transport of
      synaptic vesicle precursors showed a specific and significant decrease.
      Consequently, synaptic vesicle density decreased dramatically, and clusters of
      clear small vesicles accumulated in the cell bodies. Furthermore, marked neuronal
      degeneration and death occurred both in KIF1A mutant mice and in cultures of
      mutant neurons. The neuronal death in cultures was blocked by coculture with wild
      type neurons or exposure to a low concentration of glutamate. These results in
      cultures suggested that the mutant neurons might not sufficiently receive
      afferent stimulation, such as neuronal contacts or neurotransmission, resulting
      in cell death. Thus, our results demonstrate that KIF1A transports a synaptic
      vesicle precursor and that KIF1A-mediated axonal transport plays a critical role
      in viability, maintenance, and function of neurons, particularly mature neurons.

PMID- 9548722
TI  - Kinesin light chains are essential for axonal transport in Drosophila.
AB  - Kinesin is a heterotetramer composed of two 115-kD heavy chains and two 58-kD
      light chains. The microtubule motor activity of kinesin is performed by the heavy
      chains, but the functions of the light chains are poorly understood. Mutations
      were generated in the Drosophila gene Kinesin light chain (Klc), and the
      phenotypic consequences of loss of Klc function were analyzed at the behavioral
      and cellular levels. Loss of Klc function results in progressive lethargy,
      crawling defects, and paralysis followed by death at the end of the second larval
      instar. Klc mutant axons contain large aggregates of membranous organelles in
      segmental nerve axons. These aggregates, or organelle jams (Hurd, D.D., and W.M.
      Saxton. 1996. Genetics. 144: 1075-1085), contain synaptic vesicle precursors as
      well as organelles that may be transported by kinesin, kinesin-like protein 68D,
      and cytoplasmic dynein, thus providing evidence that the loss of Klc function
      blocks multiple pathways of axonal transport. The similarity of the Klc and Khc
      (. Cell 64:1093-1102; Hurd, D.D., and W.M. Saxton. 1996. Genetics 144: 1075-1085)
      mutant phenotypes indicates that KLC is essential for kinesin function, perhaps
      by tethering KHC to intracellular cargos or by activating the kinesin motor.

PMID- 9548723
TI  - Drosophila centrosomin protein is required for male meiosis and assembly of the
      flagellar axoneme.
AB  - Centrosomes and microtubules play crucial roles during cell division and
      differentiation. Spermatogenesis is a useful system for studying centrosomal
      function since it involves both mitosis and meiosis, and also transformation of
      the centriole into the sperm basal body. Centrosomin is a protein localized to
      the mitotic centrosomes in Drosophila melanogaster. We have found a novel isoform
      of centrosomin expressed during spermatogenesis. Additionally, an anticentrosomin
      antibody labels both the mitotic and meiotic centrosomes as well as the basal
      body. Mutational analysis shows that centrosomin is required for spindle
      organization during meiosis and for organization of the sperm axoneme. These
      results suggest that centrosomin is a necessary component of the meiotic
      centrosomes and the spermatid basal body.

PMID- 9548724
TI  - The distribution of polycomb-group proteins during cell division and development
      in Drosophila embryos: impact on models for silencing.
AB  - The subcellular three-dimensional distribution of three polycomb-group (PcG)
      proteins-polycomb, polyhomeotic and posterior sex combs-in fixed whole-mount
      Drosophila embryos was analyzed by multicolor confocal fluorescence microscopy.
      All three proteins are localized in complex patterns of 100 or more loci
      throughout most of the interphase nuclear volume. The rather narrow distribution
      of the protein intensities in the vast majority of loci argues against a PcG
      mediated sequestration of repressed target genes by aggregation into subnuclear
      domains. In contrast to the case for PEV repression (Csink, A.K., and S.
      Henikoff. 1996. Nature. 381:529-531), there is a lack of correlation between the
      occurrence of PcG proteins and high concentrations of DNA, demonstrating that the
      silenced genes are not targeted to heterochromatic regions within the nucleus.
      There is a clear distinction between sites of transcription in the nucleus and
      sites of PcG binding, supporting the assumption that most PcG binding loci are
      sites of repressive complexes. Although the PcG proteins maintain tissue-specific
      repression for up to 14 cell generations, the proteins studied here visibly
      dissociate from the chromatin during mitosis, and disperse into the cytoplasm in
      a differential manner. Quantitation of the fluorescence intensities in the whole
      mount embryos demonstrate that the dissociated proteins are present in the
      cytoplasm. We determined that <2% of PH remains attached to late metaphase and
      anaphase chromosomes. Each of the three proteins that were studied has a
      different rate and extent of dissociation at prophase and reassociation at
      telophase. These observations have important implications for models of the
      mechanism and maintenance of PcG- mediated gene repression.

PMID- 9548725
TI  - A role for Dictyostelium racE in cortical tension and cleavage furrow
      progression.
AB  - The small GTPase racE is essential for cytokinesis in Dictyostelium. We found
      that this requirement is restricted to cells grown in suspension. When attached
      to a substrate, racE null cells form an actomyosin contractile ring and complete
      cytokinesis normally. Nonetheless, racE null cells fail completely in cytokinesis
      when in suspension. To understand this conditional requirement for racE, we
      developed a method to observe cytokinesis in suspension. Using this approach, we
      found that racE null cells attempt cytokinesis in suspension by forming a
      contractile ring and cleavage furrow. However, the cells form multiple blebs and
      fail in cytokinesis by regression of the cleavage furrow. We believe this
      phenotype is caused by the extremely low level of cortical tension found in racE
      null cells compared to wild-type cells. The reduced cortical tension of racE null
      cells is not caused by a decrease in their content of F-actin. Instead, mitotic
      racE null cells contain abnormal F-actin aggregates. These results suggest that
      racE is essential for the organization of the cortical cytoskeleton to maintain
      proper cortical integrity. This function of racE is independent of attachment to
      a substrate, but can be bypassed by other signaling pathways induced by adhesion
      to a substrate.

PMID- 9548726
TI  - Accelerated nerve regeneration mediated by Schwann cells expressing a mutant form
      of the POU protein SCIP.
AB  - After injury, the peripheral nervous system (PNS) is capable of full regeneration
      and recovery of function. Many molecular events that are the hallmarks of the
      regenerating PNS are recapitulations of developmental processes. The expression
      of one such molecule, the POU transcription factor suppressed cAMP-inducible POU
      protein (SCIP), is required for the establishment of normal nerves and is
      reexpressed during regeneration. Here we describe markedly accelerated
      regeneration and hypertrophy of both myelin and axons in transgenic mice that
      express an amino-terminal deletion of the SCIP molecule. This mutant SCIP
      molecule retains the POU-specific and POU homeodomain moieties, which allow for
      both DNA binding and some protein-protein interaction. We demonstrate that the
      transgene indirectly effects dramatic axonal changes. This is the first
      demonstration of a genetically controlled acceleration of neural regeneration.

PMID- 9548728
TI  - Integrin and cadherin synergy regulates contact inhibition of migration and
      motile activity.
AB  - Integrin receptors play a central role in cell migration through their roles as
      adhesive receptors for both other cells and extracellular matrix components. In
      this study, we demonstrate that integrin and cadherin receptors coordinately
      regulate contact-mediated inhibition of cell migration. In addition to promoting
      proliferation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A. Horwitz.
      1996. J. Cell Biol. 133:169-184), ectopic expression of the alpha5 integrin in
      cultures of primary quail myoblasts promotes a striking contact-mediated
      inhibition of cell migration. Myoblasts ectopically expressing alpha5 integrin
      (alpha5 myoblasts) move normally when not in contact, but upon contact, they show
      inhibition of migration and motile activity (i.e., extension and retraction of
      membrane protrusions). As a consequence, these cells tend to grow in aggregates
      and do not migrate to close a wound. This phenotype is also seen with ectopic
      expression of beta1 integrin, paxillin, or activated FAK (CD2 FAK) and therefore
      appears to result from enhanced integrin-mediated signaling. The contact
      inhibition observed in the alpha5 myoblasts is mediated by N-cadherin, whose
      expression is upregulated more than fivefold. Perturbation studies using low
      calcium conditions, antibody inhibition, and ectopic expression of wild-type and
      mutant N-cadherins all implicate N-cadherin in the contact inhibition of
      migration. Ectopic expression of N-cadherin also produces cells that show
      inhibited migration upon contact; however, they do not show suppressed motile
      activity, suggesting that integrins and cadherins coordinately regulate motile
      activity. These observations have potential importance to normal and pathologic
      processes during embryonic development and tumor metastasis.

PMID- 9548727
TI  - p21 is a critical CDK2 regulator essential for proliferation control in Rb
      deficient cells.
AB  - Proliferation in mammalian cells is controlled primarily in the G1-phase of the
      cell cycle through the action of the G1 cyclin-dependent kinases, CDK4 and CDK2.
      To explore the mechanism of cellular response to extrinsic factors, specific loss
      of function mutations were generated in two negative regulators of G1
      progression, p21 and pRB. Individually, these mutations were shown to have
      significant effects in G1 regulation, and when combined, Rb and p21 mutations
      caused more profound defects in G1. Moreover, cells deficient for pRB and p21
      were uniquely capable of anchorage-independent growth. In contrast, combined
      absence of pRB and p21 function was not sufficient to overcome contact inhibition
      of growth nor for tumor formation in nude mice. Finally, animals with the
      genotype Rb+/-;p21(-/-) succumbed to tumors more rapidly than Rb+/- mice,
      suggesting that in certain contexts mutations in these two cell cycle regulators
      can cooperate in tumor development.

PMID- 9548731
TI  - Heterobifunctional Cross-Linkers Containing 4,9-Dioxa-1,12-dodecanediamine
      Spacers

PMID- 9548732
TI  - Identification of the upper exciton component of the B850 bacteriochlorophylls of
      the LH2 antenna complex, using a B800-free mutant of Rhodobacter sphaeroides.
AB  - In this paper, we report the circular dichroism (CD) spectra of two types of LH2
      only mutants of Rhodobacter sphaeroides. In the first, only the wild type LH2 is
      present, while i the second, the B800 binding site of LH2 has been either
      destabilized or removed. For the first time, we have identified a band in the CD
      spectrum of LH2, located at approximately 780 nm, that can be ascribed to the
      high exciton component of the B850 band. The experimental spectra have been
      modeled by theoretical calculations. On this basis, the average interaction
      strength between the monomers in the B850 ring can be estimated to be
      approximately 300 cm-1. In addition, we suggest that in LH2 of Rb. sphaeroides
      the angles made by the Qy transitions of the B850 BChls with respect to the plane
      of the ring are slightly different from those calculated from the crystal
      structure of the Rhodopseudomonas acidophila LH2 complex.

PMID- 9548729
TI  - Modulation of beta1A integrin functions by tyrosine residues in the beta1
      cytoplasmic domain.
AB  - beta1A integrin subunits with point mutations of the cytoplasmic domain were
      expressed in fibroblasts derived from beta1-null stem cells. beta1A in which one
      or both of the tyrosines of the two NPXY motifs (Y783, Y795) were changed to
      phenylalanines formed active alpha5 beta1 and alpha6 beta1 integrins that
      mediated cell adhesion and supported assembly of fibronectin. Mutation of the
      proline in either motif (P781, P793) to an alanine or of a threonine in the inter
      motif sequence (T788) to a proline resulted in poorly expressed, inactive beta1A.
      Y783,795F cells developed numerous fine focal contacts and exhibited motility on
      a surface. When compared with cells expressing wild-type beta1A or beta1A with
      the D759A activating mutation of a conserved membrane-proximal aspartate, Y783,
      795F cells had impaired ability to transverse filters in chemotaxis assays.
      Analysis of cells expressing beta1A with single Tyr to Phe substitutions
      indicated that both Y783 and Y795 are important for directed migration. Actin
      containing microfilaments of Y783,795F cells were shorter and more peripheral
      than microfilaments of cells expressing wild-type beta1A. These results indicate
      that change of the phenol side chains in the NPXY motifs to phenyl groups (which
      cannot be phosphorylated) has major effects on the organization of focal contacts
      and cytoskeleton and on directed cell motility.

PMID- 9548730
TI  - Rho-mediated contractility exposes a cryptic site in fibronectin and induces
      fibronectin matrix assembly.
AB  - Many factors influence the assembly of fibronectin into an insoluble fibrillar
      extracellular matrix. Previous work demonstrated that one component in serum that
      promotes the assembly of fibronectin is lysophosphatidic acid (Zhang, Q., W.J.
      Checovich, D.M. Peters, R.M. Albrecht, and D.F. Mosher. 1994. J. Cell Biol.
      127:1447-1459). Here we show that C3 transferase, an inhibitor of the low
      molecular weight GTP-binding protein Rho, blocks the binding of fibronectin and
      the 70-kD NH2-terminal fibronectin fragment to cells and blocks the assembly of
      fibronectin into matrix induced by serum or lysophosphatidic acid. Microinjection
      of recombinant, constitutively active Rho into quiescent Swiss 3T3 cells promotes
      fibronectin matrix assembly by the injected cells. Investigating the mechanism by
      which Rho promotes fibronectin polymerization, we have used C3 to determine
      whether integrin activation is involved. Under conditions where C3 decreases
      fibronectin assembly we have only detected small changes in the state of integrin
      activation. However, several inhibitors of cellular contractility, that differ in
      their mode of action, inhibit cell binding of fibronectin and the 70-kD NH2
      terminal fibronectin fragment, decrease fibronectin incorporation into the
      deoxycholate insoluble matrix, and prevent fibronectin's assembly into fibrils on
      the cell surface. Because Rho stimulates contractility, these results suggest
      that Rho-mediated contractility promotes assembly of fibronectin into a fibrillar
      matrix. One mechanism by which contractility could enhance fibronectin assembly
      is by tension exposing cryptic self-assembly sites within fibronectin that is
      being stretched. Exploring this possibility, we have found a monoclonal antibody,
      L8, that stains fibronectin matrices differentially depending on the state of
      cell contractility. L8 was previously shown to inhibit fibronectin matrix
      assembly (Chernousov, M.A., A.I. Faerman, M.G. Frid, O.Y. Printseva, and V.E.
      Koteliansky. 1987. FEBS (Fed. Eur. Biochem. Soc.) Lett. 217:124-128). When it is
      used to stain normal cultures that are developing tension, it reveals a matrix
      indistinguishable from that revealed by polyclonal anti-fibronectin antibodies.
      However, the staining of fibronectin matrices by L8 is reduced relative to the
      polyclonal antibody when the contractility of cells is inhibited by C3. We have
      investigated the consequences of mechanically stretching fibronectin in the
      absence of cells. Applying a 30-35% stretch to immobilized fibronectin induced
      binding of soluble fibronectin, 70-kD fibronectin fragment, and L8 monoclonal
      antibody. Together, these results provide evidence that self-assembly sites
      within fibronectin are exposed by tension.

PMID- 9548733
TI  - Generation of an angiostatin-like fragment from plasminogen by stromelysin-1 (MMP
      3).
AB  - Matrix metalloproteinase-3 (MP-3 or stromelysin-1) specifically hydrolyzes the
      Glu59-Asn60, Pro447-Val448, and Pro544-Ser545 peptide bonds in plasminogen,
      yielding a 55 kDa NH2-terminal angiostatin-like domain (comprising kringles 1-4),
      a 14 kDa domain comprising kringle 5, and a 30 kDa domain comprising the serine
      proteinases domain. The conversion is completely abolished in the presence of the
      MMP inhibitors EDTA or 1,10-phenanthroline. Biospecific interactions analysis
      indicates that binding of proMMP-3 and MMP-3 to plasminogen occurs with
      comparable affinity (KA of 4.7 x 10(6) and 4.1 x 10(6) M-1, respectively) and is
      mediated via the miniplasminogen moiety (kringle 5 plus the proteinase domain)
      and via the catalytic domain of MMP-3. Thus, proteolytic cleavage of plasminogen
      by MMP-3 generates angiostatin-like fragments.

PMID- 9548735
TI  - A permanent hole burning study of the FMO antenna complex of the green sulfur
      bacterium Prosthecochloris aestuarii.
AB  - A permanent hole burning study on the Fenna-Matthews-Olson, or FMO, antenna
      complex of the green sulfur bacterium Prosthecochloris aestuarii was carried out
      at 6 K. Excitation resulted not only in relatively sharp features resonant with
      the burn wavelength but also in broad absorbance changes in the wavelength region
      of 800-820 nm. The shape of the latter changes was almost independent of the
      wavelength of excitation. Evidence is given that they are induced by a different
      mechanism than that which causes the resonant holes and that they may be due to a
      conformational change of the protein. The original spectrum was restored upon
      warming to 60 K. The effective dephasing times T2, as obtained from the
      homogeneous line widths, increased from about 0.5 ps at 803 nm to >/=20 ps at 830
      nm and are in good agreement with recent measurements of accumulated photon-echo
      and time-resolved absorbance changes.

PMID- 9548734
TI  - The 23 and 17 kDa extrinsic proteins of photosystem II modulate the magnetic
      properties of the S1-state manganese cluster.
AB  - An S1-state parallel polarization "multiline" EPR signal arising from the oxygen
      evolving complex has been detected in spinach (PSII) membrane and core
      preparations depleted of the 23 and 17 kDa extrinsic polypeptides, but retaining
      the 33 kDa extrinsic protein. This S1-state multiline signal, with an effective g
      value of 12 and at least 18 hyperfine lines, has previously been detected only in
      PSII preparations from the cyanobacterium sp. Synechocystis sp. PCC6803
      [Campbell, K. A., Peloquin, J. M., Pham, D. P., Debus, R. J., and Britt, R. D.
      (1998) J. Am. Chem. Soc. 120, 447-448]. It is absent in PSII spinach membrane and
      core preparations that either fully retain or completely lack the 33, 23, and 17
      kDa extrinsic proteins. The S1-state multiline signal detected in spinach PSII
      cores and membranes has the same effective g value and hyperfine spacing as the
      signal detected in Synechocystis PSII particles. This signal provides direct
      evidence for the influence of the extrinsic PSII proteins on the magnetic
      properties of the Mn cluster.

PMID- 9548736
TI  - Catalase-free photosystem II: the O2-evolving complex does not dismutate hydrogen
      peroxide.
AB  - A photosystem II (PSII) membrane-associated heme catalase has been identified as
      a major source of the dark H2O2-dismutation reaction in PSII membrane samples
      [Sheptovitsky, Y. G., and Brudvig, G. W. (1996) Biochemistry 35, 16255-16263].
      Based on this finding, a catalase-free PSII membrane sample was prepared by using
      mild heat treatment to deplete most of the PSII membrane-associated heme catalase
      followed by inhibition of the residual catalase with 50 mM 3-amino-1,2,4
      triazole, a specific heme catalase inhibitor that binds covalently to compound I.
      After these treatments, the PSII membrane sample exhibited only 0.02% of the
      original H2O2-dismutation activity when assayed in the presence of 20 mM 3-amino
      1,2,4-triazole. This small residual H2O2-dismutation activity is attributed to
      adventitious metal ions or the non-heme iron in PSII because the activity was
      still present in a Mn-depleted PSII sample but was completely suppressed by
      adding 5 mM ferricyanide to the assay buffer; the effect of ferricyanide is
      attributed to oxidation of H2O2-dismutating cations. Although the H2O2
      dismutation activity was completely eliminated by these treatments, the light
      induced O2-evolution activity was retained. A single saturating flash given to
      catalase-free PSII membranes did not induce any H2O2-dismutation activity. These
      results demonstrate that the S1/S-1 and S2/S0 cycles of the O2-evolving complex
      of PSII do not occur in the presence of H2O2, as proposed by Velthuys, B., and
      Kok, B. [(1978) Biochim. Biophys. Acta 502, 211-221]. The light-induced O2
      evolution activity in catalase-free PSII was found to be irreversibly impaired by
      micromolar concentrations of H2O2. Thus, it is possible that the PSII membrane
      associated heme catalase plays an important role in protection of the O2-evolving
      complex from damage by H2O2.

PMID- 9548737
TI  - Dynamics of the DNA binding domain of the fructose repressor from the analysis of
      linear correlations between the 15N-1H bond spectral densities obtained by
      nuclear magnetic resonance spectroscopy.
AB  - The spectral densities of the backbone and arginine side chain NH bonds of the
      DNA binding domain of the fructose repressor (FruR) were extensively analyzed in
      order to extract reliable motions parameters. An accurate measurement of 15N NMR
      relaxation rates allowed their calculation at three frequencies, zero, omegaN,
      and omegaH + omegaN, using a reduced matrix approach. Linear correlations were
      found between J(omegaN) and J(0) and between <J(omegaH)> and J(0). The analysis
      of the compatibility between the motions parameters obtained independently from
      the two correlation lines allowed further development of the linear correlation
      approach proposed recently [Lefevre, J. F., Dayie, K. T., Peng, J. W., and
      Wagner, G. (1996) Biochemistry 35, 2674-2686]. The results demonstrate (i) the
      existence of a concerted motion along the whole backbone with a global
      correlation time equal to 5.95 ns.rad-1, and (ii) the presence of complex
      internal movements at an intermediate time scale around 1 ns. The extracted
      motion parameters have been related to those obtained with the extended Lipari
      and Szabo approach but are incompatible with those obtained using the usual
      simple Lipari and Szabo approach. They were correlated to the features of the NMR
      structure of FruR(1-57)*. Some residues in the turns and in the third helix
      experience slow motions in the micro- to millisecond time scale. Side-chain
      motions are not correlated to the backbone dynamics. A direct examination of
      spectral densities reveals a higher flexibility for the side chains of arginines
      that are not involved in ionic bridges.

PMID- 9548738
TI  - The crystal structure of phosphoribulokinase from Rhodobacter sphaeroides reveals
      a fold similar to that of adenylate kinase.
AB  - The essential photosynthetic enzyme phosphoribulokinase (PRK) is responsible for
      the conversion of ribulose 5-phosphate (Ru5P) to ribulose 1,5-bisphosphate, the
      substrate for the CO2 fixing enzyme ribulose 1,5-bisphosphate
      carboxylase/oxygenase (Rubisco). We have determined the structure of the
      octameric bacterial form of PRK to a resolution of 2.5 A. The protein is folded
      into a seven-member mixed beta-sheet surrounded by alpha-helices, giving the
      overall appearance of the nucleotide monophosphate family of kinases. Homology
      with the nucleotide monophosphate kinases suggests a number of amino acid
      residues that are likely to be important in catalysis and suggests the roles of
      some amino acid residues that have been mutated prior to the determination of the
      structure. Further, sequence identity across eukaryotic and prokaryotic species
      and a calculation of the buried surface area suggests the identity within the
      octamer of a dimer conserved throughout evolution. The width of the groove
      leading to the active site is consistent with an oriented molecule of thioredoxin
      controlling the oxidation state of two cysteines that regulate activity in the
      eukaryotic enzymes. Although neither Asp 42 nor Asp 169 can be definitively
      assigned as the catalytic base, the crystal structure suggests the location of a
      ribulose 5-phosphate binding site and suggests a role for several of the
      conserved basic residues.

PMID- 9548739
TI  - A new class of HIV-1 Tat antagonist acting through Tat-TAR inhibition.
AB  - The main transcriptional regulator of the human immunodeficiency virus, the Tat
      protein, recognizes and binds to a small structured RNA element at the 5' end of
      every viral mRNA, termed TAR. On the basis of published structural data of the
      molecular interactions between TAR and Tat-related peptides, we defined
      requirements for potential low-molecular weight inhibitors of TAR recognition by
      the Tat protein. In accordance with the resulting concept, a series of compounds
      was synthesized. In vitro evaluation of their potential to directly interfere
      with Tat-TAR interaction was used to define a new chemical class of potent Tat
      antagonistic substances. The most active compound competed with Tat-TAR
      complexation with a competition dose CD50 of 22 nM in vitro and blocked HIV
      expression in a cellular Tat transactivation system with an IC50 of 1.2 microM.
      The close relation between structural features of the interaction between TAR and
      a new type of inhibitory agent, "In-PRiNts" (for inhibitor of protein
      ribonucleotide sequences), such as CGP 40336A and those of the Tat-TAR complex
      was confirmed by RNase A footprinting and by two-dimensional NMR. Structural
      implications for the complex between this class of compounds and TAR RNA will be
      presented.

PMID- 9548740
TI  - Biochemical characterization and crystallographic structure of an Escherichia
      coli protein from the phosphotriesterase gene family.
AB  - Phosphotriesterase homology protein (PHP) is a member of a recently discovered
      family of proteins related to phosphotriesterase, a hydrolytic, bacterial enzyme
      with an unusual substrate specificity for synthetic organophosphate triesters and
      phosphorofluoridates, which are common constituents of chemical warfare agents
      and agricultural pesticides. No natural substrate has been identified for
      phosphotriesterase, and it has been suggested that the enzyme may have evolved
      the ability to hydrolyze synthetic compounds in bacteria under selective pressure
      to meet nutritional needs. PHP, which has 28% sequence identity with
      phosphotriesterase, may belong to the family of proteins from which
      phosphotriesterase evolved. Here we report the cloning, expression, initial
      characterization, and high-resolution X-ray crystallographic structure of PHP.
      Biochemical analysis shows that PHP is monomeric and binds two zinc ions per
      monomer. Unlike phosphotriesterase, PHP does not catalyze the hydrolysis of
      nonspecific phosphotriesters. The structure, similar to that of
      phosphotriesterase, consists of a long, elliptical alpha/beta barrel and has a
      binuclear zinc center in a cleft at the carboxy end of the barrel at the location
      of the presumptive active site.

PMID- 9548741
TI  - Structure of bovine pancreatic cholesterol esterase at 1.6 A: novel structural
      features involved in lipase activation.
AB  - The structure of pancreatic cholesterol esterase, an enzyme that hydrolyzes a
      wide variety of dietary lipids, mediates the absorption of cholesterol esters,
      and is dependent on bile salts for optimal activity, is determined to 1.6 A
      resolution. A full-length construct, mutated to eliminate two N-linked
      glycosylation sites (N187Q/N361Q), was expressed in HEK 293 cells. Enzymatic
      activity assays show that the purified, recombinant, mutant enzyme has activity
      identical to that of the native, glycosylated enzyme purified from bovine
      pancreas. The mutant enzyme is monomeric and exhibits improved homogeneity which
      aided in the growth of well-diffracting crystals. Crystals of the mutant enzyme
      grew in space group C2, with the following cell dimensions: a = 100.42 A, b =
      54.25 A, c = 106.34 A, and beta = 104.12 degrees, with a monomer in the
      asymmetric unit. The high-resolution crystal structure of bovine pancreatic
      cholesterol esterase (Rcryst = 21.1%; Rfree = 25.0% to 1.6 A resolution) shows an
      alpha-beta hydrolase fold with an unusual active site environment around the
      catalytic triad. The hydrophobic C terminus of the protein is lodged in the
      active site, diverting the oxyanion hole away from the productive binding site
      and the catalytic Ser194. The amphipathic, helical lid found in other
      triglyceride lipases is truncated in the structure of cholesterol esterase and
      therefore is not a salient feature of activation of this lipase. These two
      structural features, along with the bile salt-dependent activity of the enzyme,
      implicate a new mode of lipase activation.

PMID- 9548742
TI  - Protein-induced changes in nonplanarity of the porphyrin in nickel cytochrome c
      probed by resonance Raman spectroscopy.
AB  - The influence of the protein on the nonplanarity of the macrocycle for nickel(II)
      reconstituted cytochrome c (NiCyt-c) has been investigated with pH-dependent
      resonance Raman and UV-visible absorption spectroscopy and molecular mechanics
      calculations. The spectra reveal that NiCyt-c near neutral pH has axially
      coordinated Ni, but below pH 3 and above pH 12, four-coordinate species
      predominate. The shape of the structure-sensitive Raman line nu10 of NiCyt-c is
      asymmetric and broad and it changes with pH. This broad line can be decomposed
      well into at least two sublines, a low-frequency line that results from a
      nonplanar conformer and a high-frequency line that arises from a nearly planar
      conformer. Upon lowering the pH from 3.0 to 1.0, the amount of the nonplanar
      conformer decreases relative to that of the planar conformer. The decreased
      nonplanarity can be accounted for in terms of the disruption of a hydrogen
      bonding network in the peptide backbone upon lowering the pH. Molecular mechanics
      (MM) calculations on iron(III) and nickel(II) microperoxidase 5 (MP-5) as well as
      some model heme derivatives have been carried out in order to locate the part of
      the protein that causes the heme distortion observed in the X-ray crystal
      structures of cytochromes c. The energy-optimized structures of MP-5 and the
      model compounds were analyzed using the normal-coordinate structural
      decomposition method to specify and quantify the out-of-plane macrocyclic
      distortions. MM calculations for MP-5 show that two hydrogen bonds formed between
      the amide groups in the peptide backbone are important in maintaining the ruffled
      deformation of the macrocycle. All evidence presented supports the hypothesis
      that the nonplanar distortion of the porphyrin of cytochromes c is largely
      maintained by a relatively small protein segment including the cysteines, the
      amino acids between the cysteines, and the adjacent histidine ligand. Hydrogen
      bonding within the backbone of this segment is important in maintaining the
      conformation of the peptide that induces the porphyrin distortion.

PMID- 9548743
TI  - Hydroxyl radical footprinting of DNA complexes of the ets domain of PU.1 and its
      comparison to the crystal structure.
AB  - Hydroxyl radical footprinting has been used to probe interactions in complexes
      between the ets domain of the murine transcription factor PU.1 and three
      different DNA restriction fragments, each containing one copy of the recognition
      sequence 5'-GGAA-3'. Two natural PU.1 binding sites, the SV40 enhancer site and
      the lambdaB motif of Ig lambda2-4 enhancer, were used as well as the PU.1 binding
      site present in the crystallized PU.1-DNA complex [Kodandapani, R., Pio, F., Ni,
      C.-Z., Piccialli, G., Klemsz, M., McKercher, S. R., Maki, R. A., and Ely, K. R.
      (1996) Nature 380, 456-460]. The footprints obtained for the three different DNA
      sequences are almost identical. The extent of contact with the protein was
      monitored for every base in the complex. Two concentration-dependent cleavage
      sites on the complementary TTCC strand are evidence of a specific interaction
      between PU.1 and the DNA. Two more protection sites and a hypersensitive cleavage
      site on the GGAA strand were observed. Although these data confirm the global
      structure of the PU.1-DNA complex as suggested by crystallography, the
      footprinting data reveal differences between the protein-DNA contacts in solution
      and in the crystal state. An additional interaction site not present in the
      crystal structure was observed by hydroxyl radical footprinting.

PMID- 9548745
TI  - Aminoacylation of coenzyme A and pantetheine by aminoacyl-tRNA synthetases:
      possible link between noncoded and coded peptide synthesis.
AB  - Isoleucyl-tRNA synthetase (IleRS) catalyzes transfer of isoleucine from the
      enzyme-bound Ile-AMP and Ile-tRNA to the thiol group of coenzyme A, forming a
      thioester, Ile-S-CoA. Identity of Ile-S-CoA has been confirmed by several
      enzymatic and chemical tests. The synthesis of Ile-S-CoA, like the synthesis of
      other isoleucyl thioesters, is strongly shifted toward products. Other aminoacyl
      tRNA synthetases, such as MetRS, AspRS, and SerRS also use CoA-SH as an acceptor
      for their cognate amino acids. Pantetheine also serves as an amino acid acceptor
      in reactions catalyzed by AspRS, IleRS, and MetRS, forming corresponding
      aminoacyl-S-pantetheine thioesters. It appears that CoA-SH reacts with activated
      amino acids by binding to each synthetase at a site, separate from the tRNA and
      ATP binding sites, that includes the thiol-binding subsite. These and other data
      support a hypothesis that the present-day aminoacyl-tRNA synthetases have
      originated from ancestral forms that were involved in noncoded thioester
      dependent peptide synthesis, functionally similar to the present-day nonribosomal
      peptide synthesis by multi-enzyme thiotemplate systems.

PMID- 9548744
TI  - The DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and
      inhibits primarily DNA synthesis in B16 melanoma cells.
AB  - Cryptolepine hydrochloride is an indoloquinoline alkaloid isolated from the roots
      of Cryptolepis sanguinolenta. It is characterized by a multiplicity of host
      mediated biological activities, including antibacterial, antiviral, and
      antimalarial properties. To date, the molecular basis for its diverse biological
      effects remains largely uncertain. Several lines of evidence strongly suggest
      that DNA might correspond to its principal cellular target. Consequently, we
      studied the strength and mode of binding to DNA of cryptolepine by means of
      absorption, fluorescence, circular, and linear dichroism, as well as by a
      relaxation assay using DNA topoisomerases. The results of various optical and gel
      electrophoresis techniques converge to reveal that the alkaloid binds tightly to
      DNA and behaves as a typical intercalating agent. In DNAase I footprinting
      experiments it was found that the drug interacts preferentially with GC-rich
      sequences and discriminates against homo-oligomeric runs of A and T. This study
      has also led to the discovery that cryptolepine is a potent topoisomerase II
      inhibitor and a promising antitumor agent. It stabilizes topoisomerase II-DNA
      covalent complexes and stimulates the cutting of DNA at a subset of preexisting
      topoisomerase II cleavage sites. Taking advantage of the fluorescence of the
      indoloquinoline chromophore, fluorescence microscopy was used to map cellular
      uptake of the drug. Cryptolepine easily crosses the cell membranes and
      accumulates selectively into the nuclei rather than in the cytoplasm of B16
      melanoma cells. Quantitative analyses of DNA in cells after Feulgen reaction and
      image cytometry reveal that the drug blocks the cell cycle in G2/M phases. It is
      also shown that the alkaloid is more potent at inhibiting DNA synthesis rather
      than RNA and protein synthesis. Altogether, the results provide direct evidence
      that DNA is the primary target of cryptolepine and suggest that this alkaloid is
      a valid candidate for the development of tumor active compounds.

PMID- 9548746
TI  - RNase H1 can catalyze RNA/DNA hybrid formation and cleavage with stable hairpin
      or duplex DNA oligomers.
AB  - Cleavage of a RNA target site by RNase H1 from Escherichia coli was examined in
      the presence of complementary DNA sequences in the form of single-stranded,
      duplex, and hairpin structures. The target site was a 15 nt sequence in the
      middle of a 79 nt RNA transcript. DNA molecules employed included seven single
      stranded oligodeoxynucleotides 10 or 15 nt long, and five hairpin DNAs each with
      a 10 bp stem and 5 nt loop. The loop and 3' side of the stem of two of the
      hairpin DNAs were fully complementary to the target site, while the other hairpin
      DNAs had sequence changes. A 10 bp duplex DNA with one strand complementary to
      the target site was also employed. A gel electrophoresis mobility shift assay
      examined hybrid formation between the RNA and the single-stranded 15 nt DNA and
      two hairpin DNAs that contained 15 complementary bases. RNA titration of the 32P
      labeled single-stranded DNA produced a shifted band indicative of RNA/DNA complex
      formation. No RNA/DNA complex was detected when the more stable (Tm = 71 degrees
      C) hairpin DNA was combined with excess RNA. The less stable hairpin DNA (Tm = 62
      degrees C) showed a small amount ( approximately 8%) of hybrid formation.
      Thermodynamic analysis of RNA binding to the DNAs was in qualitative agreement
      with the results. Although no RNA/DNA hybrid was expected from thermodynamic
      calculations, a RNase H assay at 25 degrees C showed that hairpin or duplex DNAs
      with a 10 nt complementary sequence catalyzed RNA degradation. A complementary
      loop sequence in the hairpin DNA was not required. Cleavage of the RNA did not
      occur with hairpin DNAs containing three or four noncomplementary bases in the
      stem. The results show that RNase H can promote the formation and cleavage of a
      RNA/DNA hybrid between an RNA site and a base paired strand of a stable hairpin
      or duplex DNA at temperatures below their Tm.

PMID- 9548747
TI  - Euplotes telomerase: evidence for limited base-pairing during primer elongation
      and dGTP as an effector of translocation.
AB  - The telomeric sequence repeats at the ends of eukaryotic chromosomes are
      maintained by the ribonucleoprotein enzyme telomerase. Telomeric DNA primers are
      bound by telomerase both at the active site, which includes base-pairing with the
      RNA template, and at a second anchor site. The stabilities of Euplotes
      aediculatus primer-telomerase complexes were determined by measuring their
      dissociation rates (koff), using an assay involving photo-cross-linking at the
      anchor site. The primer length was varied, and mismatched substitutions were
      introduced in a systematic manner. We observed that koff does not scale with
      primer length as expected for accumulated primer-template base-pairing. This
      suggests that telomerase maintains a more-or-less constant number of base pairs,
      similar to the transcription bubble maintained by RNA polymerase. An upper limit
      was estimated by comparing the experimental koff for the primer-telomerase
      complex to that of a model DNA-RNA duplex. All the binding energy could be
      attributed to 10 or 11 base pairs; alternatively, there could be <10 base pairs,
      with the remaining energy contributed by other parts of telomerase. Most primers
      exhibited biphasic dissociation kinetics, with variations in both the amount in
      each phase and the rate for each phase. Since the cross-links monitored in the
      dissociation assay were all formed with the 5' region of the primer, the two
      phases may arise from different base-pairing registers with the RNA template,
      possibly representing pre- and post-translocation complexes. A shift from slow
      phase to fast phase dissociation was observed in the presence of dGTP, which may
      implicate dGTP as a positive effector of translocation.

PMID- 9548748
TI  - Single amino acid substitutions at the N-terminus of a recombinant cytotoxic
      ribonuclease markedly influence biochemical and biological properties.
AB  - Onconase is a cytotoxic ribonuclease with antitumor properties. A semisynthetic
      gene encoding the entire protein sequence was constructed by fusing
      oligonucleotides coding for the first 15 and the last 6 of the 104 amino acids to
      a genomic clone that encoded the remaining amino acid residues [Newton, D. L., et
      al. (1997) Protein Eng. 10, 463-470]. The resulting protein product expressed in
      Escherichia coli exhibited little enzymatic or cytotoxic activity due to the
      unprocessed N-terminal Met amino acid residue. In this study, we demonstrate that
      modification of the 5'-region of the gene to encode [Met-(-1)]Ser or [Met-(
      1)]Tyr instead of the native pyroglutamate results in recombinant onconase
      derivatives with restored activities. [Met-(-1)]rOnc(E1S) was more active than
      [Met-(-1)]rOnc(E1Y) in all assays tested. Consistent with the action of native
      onconase, [Met-(-1)]rOnc(E1S) was a potent inhibitor of protein synthesis in the
      cell-free rabbit reticulocyte lysate assay, degrading tRNA at concentrations that
      correlated with inhibition of protein synthesis. An interesting difference
      between the recombinant onconase derivatives and the native protein was their
      susceptibility to inhibition by the major intracellular RNase inhibitor, PRI
      (onconase is refractory to PRI inhibition). [Met-(-1)]rOnc(E1S) and [Met-(
      1)]rOnc(E1Y) inhibited protein synthesis in intact SF539 neuroblastoma cells with
      IC50's very similar to that of onconase (IC50 3.5, 10, and 10 microg/mL after 1
      day and 0.16, 0.35, and 2.5 microg/mL after 5 days for onconase, [Met-(
      1)]rOnc(E1S), and [Met-(-1)]rOnc(E1Y), respectively). Similar to that of
      onconase, cytotoxic activity of the recombinant derivatives was potentiated by
      monensin, NH4Cl, and retinoic acid. Brefeldin A completely blocked the
      enhancement of cytotoxicity caused by retinoic acid with all three proteins.
      Thus, drug-induced alterations of the intracellular trafficking of the
      recombinant derivatives also resembles that of onconase. Stability studies as
      assessed in serum-containing medium in the presence or absence of cells at 37
      degreesC showed that the recombinant proteins were as stable to temperature and
      cell culture conditions as the native protein. Therefore, exchanging the Glu
      amino acid residue at the amino terminus of onconase with an amino acid residue
      containing a hydroxyl group produces recombinant proteins with ribonuclease and
      cytotoxic properties similar to native onconase.

PMID- 9548749
TI  - Misincorporation of nucleotides opposite five-membered exocyclic ring guanine
      derivatives by escherichia coli polymerases in vitro and in vivo: 1,N2
      ethenoguanine, 5,6,7,9-tetrahydro-9-oxoimidazo[1, 2-a]purine, and 5,6,7,9
      tetrahydro-7-hydroxy-9-oxoimidazo[1, 2-a]purine.
AB  - A variety of exocyclic modified bases have been shown to be formed in DNA from
      various procarcinogens (e.g., acrolein, malonaldehyde, vinyl chloride, urethan)
      and are also found in untreated animals and humans, presumably arising as a
      result of lipid peroxidation. 1, N2-Ethenoguanine (1,N2-epsilon-Gua), a product
      known to be formed from several 2-carbon electrophiles, was placed in a known
      site (6256) in bacteriophage M13MB19 and mutations were analyzed in Escherichia
      coli, with 2.05% G-->A, 0.74% G-->T, and 0.09% G-->C changes found in uvrA-
      bacteria. 5,6,7, 9-Tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine (HO-ethanoGua),
      formally the hydrated derivative of 1,N2-epsilon-Gua, is a stable DNA product
      also derived from vinyl halides. When this base was placed in the same context,
      the mutation rate was 0.007-0.19% for G-->A, C, or T changes. The saturated
      etheno ring derivative of 1, N2-epsilon-Gua, 5,6,7,9-tetrahydro-9-oxoimidazo[1,2
      a]purine (ethanoGua) produced G-->A and G-->T mutations (0.71% each). All mutants
      were SOS-dependent and were attenuated by uvrA activity in E. coli. In vitro
      studies with four polymerases showed strong blocks to addition beyond the adduct
      site in the order ethanoGua > HO-ethanoGua > 1,N2-epsilon-Gua. Both E. coli
      polymerases (pol) I exo- and II exo- and bacteriophage pol T7 exo- showed
      extensive misincorporation opposite ethanoGua in vitro, with pol I exo-
      incorporating G and T, pol II exo- incorporating A, and pol T7 exo- incorporating
      A and G. All modified bases reduced the use of the minus strand bearing the
      modified guanine in E. coli cells. It is of interest that even though the normal
      base pairing site of guanine is completely blocked, all of the five-membered ring
      derivatives incorporate the normal base (C) in >80% of the replication events in
      E. coli. Major differences in blockage and misincorporation are seen due to what
      might appear to be relatively modest structural differences, and polymerases can
      differ dramatically in their selectivities.

PMID- 9548750
TI  - Escherichia coli cAMP receptor protein-DNA complexes. 1. Energetic contributions
      of half-sites and flanking sequences in DNA recognition.
AB  - In Escherichia coli, the cyclic AMP receptor protein (CRP) serves as a sensor of
      the intracellular level of cyclic AMP. At increasing concentrations of cyclic
      AMP, CRP becomes activated upon binding a cyclic AMP molecule. The activated CRP
      is capable of regulating the expression of more than 20 genes by binding to
      specific DNA sites. The specific DNA sequences recognized by CRP consist of two
      half-sites of the consensus sequence TGTGA......XCAXA. At present, the relative
      contributions of the two half-site and flanking sequences in the energetics of
      CRP recognition have not been quantitatively defined. A series of 20 DNA
      sequences was designed to dissect the contributions of individual half-sites and
      flanking sequences using the natural gal P1 and lac P1 sequences as the initial
      targets. The binding of CRP to these DNA sequences was monitored by fluorescence
      anisotropy. None of the individual half-sites or flanking sequences contributes
      more to the binding energetics than a random sequence. In the lac P1 sequence,
      the combination of both half-sites leads to a >100-fold increase in affinity
      compared to that of an individual half-site in CRP-DNA complex formation. The
      flanking sequence of lac P1 exhibits a 10- and 0-fold enhancement in affinity for
      CRP compared to that of a random sequence in the presence and absence of the two
      half-sites, respectively. The observations of the gal P1 sequence differ from
      those of the lac P1 sequence. The combination of both half-sites exhibits no
      significant increase in affinity, but the flanking sequence exhibits a 100-fold
      enhancement in the presence of the two half-sites. However, there is a
      disproportionate contribution from the flanking sequence proximal to the
      conserved TGTGA motif. The total energetics of the gal-CRP complex formation is
      essentially due to the presence of the conserved half-site and its adjacent
      flanking sequence. Thus, the relative contributions of the half-site and flanking
      sequences to the energetics of DNA recognition are operon specific.

PMID- 9548751
TI  - Escherichia coli cAMP receptor protein-DNA complexes. 2. Structural asymmetry of
      DNA bending.
AB  - The effect of DNA sequence variability and the degree of cyclic AMP receptor
      protein (CRP)-induced bending of the flanking ends of fluorescently labeled DNA
      were investigated by steady-state fluorescence and differential phase
      polarization studies in the presence and absence of CRP. Six sequences, including
      the primary CRP binding sites of lac P1 (class I) and gal P1 (class II), were
      studied. Excitation and emission spectra of CPM-DNA upon binding CRP were
      observed to be qualitatively similar to one another, regardless of the CRP
      binding site sequence examined or the location of the probe. This result implies
      that the probe is not interacting with the protein. However, the magnitude of the
      changes in the fluorescence intensities of sensitized emission spectra of CPM-DNA
      is apparently dependent on the DNA sequence, indicating that the environments of
      the flanking ends of DNA may be different from one another in the protein-DNA
      complex. Differential phase polarization results were qualitatively consistent
      with the fluorescence energy transfer measurements. The implication of this study
      supports the idea that the DNA is bent symmetrically in the lac-CRP complex but
      is asymmetrically bent in the gal-CRP complex. The sequence in the half-site in
      conjunction with the flanking sequence defines the geometry of the bent DNA. It
      appears that the CRP-induced bend in the DNA may also be class dependent. This
      may be an important feature used by the system to regulate transcription at
      different promoter sites.

PMID- 9548752
TI  - Effect of nucleosome structure on DNA interstrand cross-linking reactions.
AB  - Antitumor agents of the nitrogen mustard family and mitomycin C form interstrand
      cross-links in duplex DNA. To provide information about the cellular mechanism by
      which these compounds exert their cytotoxic effects, we examined cross-linking of
      a nucleosomal core particle formed on a fragment of the 5S RNA gene of Xenopus
      borealis. For the mustards mechlorethamine, chlorambucil, and melphalan, both
      sites of monoalkylation and interstrand cross-linking were similar in nucleosomal
      and free DNA. Some small (two- to three- fold) differences in intensity of cross
      linking at some sites were apparent. However, these differences did not appear to
      correlate with rotational or translational positioning. For mitomycin C, cross
      linking was inhibited five- to ten-fold at the nucleosomal dyad and showed
      attenuation of inhibition toward the ends. Furthermore, rotational positioning
      also appeared to be a factor, with sites facing inward in the nucleosome less
      accessible for mitomycin cross-linking. None of these agents demonstrated the 10
      base pair periodicity exhibited by hydroxyl radical cleavage of nucleosomal DNA.

PMID- 9548753
TI  - Formation of native disulfide bonds in endothelin-1. Structural evidence for the
      involvement of a highly specific salt bridge between the prosequence and the
      endothelin-1 sequence.
AB  - The [Lys-Arg]-endothelin-1 analogue (KR-ET-1) yields almost selectively the
      native disulfide pattern (96%), in contrast to endothelin-1 (ET-1) that gives at
      least 25% of the non-native disulfide pattern. We have previously shown that the
      carboxylate-state structure of KR-ET-1 is more constrained and stabilized by a
      salt bridge between Arg(-1) and the Asp8 or Glu10 side chain [Aumelas et al.
      (1995) Biochemistry 34, 4546-4561]. To identify this salt bridge and its
      potential involvement in the disulfide bond formation, [E10Q], [D18N], and [D8N]
      carboxamide analogues were studied, which led to the unambiguous identification
      of the Arg(-1)-Asp8 salt bridge. Furthermore, while [E10Q] and [D18N] analogues
      gave a high yield of the native isomer (>/=90%), the [D8N] analogue afforded a
      ratio of the two isomers close to that observed for ET-1 (68%) [Kubo et al.
      (1997) Lett. Pept. Sci. 4, 185-192]. Assuming that the formation of disulfide
      bonds occurs in a thermodynamically controlled step, we have hypothesized that
      the Arg(-1)-Asp8 salt bridge and concomitant interactions could be responsible
      for the increase in yield of the native isomer of KR-ET-1. In the present work,
      we describe the structural studies of the carboxamide analogues and of the minor
      non-native KR-ET-1 isomer. On the basis of 1H NMR and CD spectra as a function of
      pH, [E10Q] and [D18N] analogues display a conformational change similar to that
      of the parent peptide, whereas the structure of the [D8N] analogue is unchanged.
      For the non-native isomer, we measured a lower helical content than for the
      native isomer and observed a marked difference in the orientation of the KRCSC
      backbone. In addition, no salt bridge was experimentally observed. Altogether,
      these results allow us to hypothesize that the salt bridge between two highly
      conserved residues, one belonging to the prosequence [Arg(-1)] and the other to
      the mature sequence [Asp8], is involved in the formation of the native disulfide
      isomer of ET-1. The involvement of the prosequence in the formation of the native
      disulfide isomer strongly suggests that, in the maturation pathway of ET-1,
      cleavage of the Arg52-Cys53 amide bond occurs after native disulfide bond
      formation.

PMID- 9548754
TI  - ATP-Dependent human erythrocyte glutathione-conjugate transporter. I.
      Purification, photoaffinity labeling, and kinetic characteristics of ATPase
      activity.
AB  - Dinitrophenyl S-glutathione (DNP-SG) ATPase is a 38 kDa membrane protein
      expressed in erythrocytes and other tissues. Although stimulation of ATP
      hydrolysis catalyzed by DNP-SG ATPase has been demonstrated in the presence of
      several structurally unrelated amphiphilic ions, structural and functional
      properties of this protein have not been well-defined. In the present study, we
      have developed an improved protocol for the purification of DNP-SG ATPase and
      investigated its kinetic and substrate-binding properties. The purification
      procedure was based on highly specific elution of the 38 kDa protein from DNP-SG
      affinity resin in the presence of ATP. The protein could not be eluted using
      either ADP or adenosine-5'-[beta,gamma-methylene]triphosphate (methylene-ATP), a
      nonhydrolyzable analogue of ATP. Doxorubicin (DOX), a weakly basic anthracycline
      chemotherapy agent, was found to be the preferred activator for stimulation of
      ATP hydrolysis by the enzyme. ATP binding to the enzyme was demonstrated using 8
      azido-ATP photoaffinity labeling and binding of trinitrophenyl (TNP)-ATP, a
      fluorescent analogue of ATP. The photoaffinity labeling of DNP-SG ATPase (38 kDa)
      was saturable with respect to 8-azido ATP (Kd = 2 microM), indicating that the
      enzyme was capable of specific and saturable binding to ATP. DNP-SG binding was
      evident from the purification procedure itself and was also demonstrable by
      quenching of tryptophan fluorescence. Results of quenching of tryptophan
      fluorescence as well as radioactive isotope-binding studies indicated that DOX
      was bound to the purified protein as well.

PMID- 9548755
TI  - ATP-Dependent human erythrocyte glutathione-conjugate transporter. II. Functional
      reconstitution of transport activity.
AB  - Purified dinitrophenyl S-glutathione (DNP-SG) ATPase was reconstituted into
      artificial liposomes prepared from soybean asolectin. Electron micrography
      confirmed the formation of unilamellar vesicles with an average radius of 0.25
      micron. Intravesicular volume estimated by incorporation of radiolabled inulin
      into the vesicles was found to be 19.7 +/- 1.3 microL/mL reconstitution solution.
      Accumulation of the glutathione-conjugate of CDNB, DNP-SG, and of doxorubicin
      (DOX) in the proteoliposomes was increased in the presence of ATP as compared to
      equimolar ADP or adenosine 5'-[beta,gamma-methylene]triphosphate tetralithium.
      ATP-dependent transmembrane movement of DOX and DNP-SG into DNP-SG ATPase
      reconstituted vesicles was saturable with respect to time, sensitive to the
      osmolarity of the assay medium, and temperature dependent. The energy of
      activation was found to be 12 and 15 kcal/mol for DNP-SG and DOX, respectively.
      Optimal temperature for transport was 37 degrees C. Saturable transport was
      demonstrated for DNP-SG (Vmax of 433 +/- 20 nmol/min/mg of protein, KmATP = 2.4
      +/- 0. 3 mM and KmDNP-SG = 36 +/- 5 microM) as well as DOX (Vmax = 194 +/- 19
      nmol/min/mg of protein, KmATP = 2.5 +/- 0.6 mM and KmDOX = 2.4 +/- 0.7 microM).
      The kinetic data for both DNP-SG and DOX transport were consistent with a random
      bi-bi sequential reaction mechanism. DOX was found to be a competitive inhibitor
      of DNP-SG transport with Kis of 1.2 +/- 0.2 microM and DNP-SG was found to be a
      competitive inhibitor of DOX transport with Kis of 13.3 +/- 2.6 microM.

PMID- 9548756
TI  - Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190,
      p50RhoGAP, Bcr, and 3BP-1.
AB  - The small GTP-binding protein RhoA becomes inactivated by hydrolyzing bound GTP
      to GDP through its intrinsic GTPase activity which is further stimulated by a
      family of Rho GTPase-activating proteins (GAPs). Here we have compared the
      kinetics of interaction between recombinant RhoA and the RhoGAP domains of p190,
      p50RhoGAP, Bcr, and 3BP-1. The intrinsic rate of GTP hydrolysis by RhoA is
      relatively slow when compared to other Rho-family GTPases such as Cdc42 or Rac1
      with a rate constant of 0.022 min-1, which can be further stimulated at least
      4000-fold by p190 or p50RhoGAP. The RhoGAP domains of Bcr and 3BP-1, which were
      thought to be inactive toward RhoA, are also found capable of stimulating the
      GTPase activity of RhoA in a dose-dependent manner. The supreme catalytic
      activities of p190 and p50RhoGAP toward RhoA reside mostly in their lower Km
      values (1.79 and 2.83 microM, respectively) which correlate well with their
      binding affinity for GMP-PNP-bound RhoA (2.18 and 2. 47 microM, respectively), in
      contrast with Bcr and 3BP-1 which interact with the activated RhoA with much
      higher Km (89 microM). However, the mechanisms of catalysis by p190 and p50RhoGAP
      are distinct in at least three aspects: (1) p50RhoGAP displays an effect of
      product inhibition by binding to the GDP-bound form of RhoA with a Kd of 6 microM
      in comparison with the Kd for p190 of 33 microM; (2) the Km of p190 increases
      drastically upon the increase of salt and Mg2+ concentrations, conditions under
      which only modest changes of Km for p50RhoGAP are observed; and (3) p50RhoGAP
      remains partially active toward the effector domain mutants of RhoA, Y34K, and
      T37A, whereas p190 is completely inactive toward Y34K and T37A. These results
      suggest that there exists a unique mechanism of functional interaction between
      RhoA and individual RhoGAP which involves distinct structural determinants of the
      small G-protein to cause the apparent differences in kinetic properties.

PMID- 9548757
TI  - Cross-class inhibition of the cysteine proteinases cathepsins K, L, and S by the
      serpin squamous cell carcinoma antigen 1: a kinetic analysis.
AB  - The human squamous cell carcinoma antigens (SCCA) 1 and 2 are tandemly arrayed
      genes that encode two high-molecular-weight serine proteinase inhibitors
      (serpins). Although these proteins are 92% identical, differences in their
      reactive site loops suggest that they inhibit different types of proteinases. Our
      previous studies show that SCCA2 inhibits chymotrypsin-like serine proteinases
      [Schick et al. (1997) J. Biol. Chem. 272, 1849-1855]. We now show that, unlike
      SCCA2, SCCA1 lacks inhibitory activity against any of the more common types of
      serine proteinases but is a potent cross-class inhibitor of the archetypal
      lysosomal cysteine proteinases cathepsins K, L, and S. Kinetic analysis revealed
      that SCCA1 interacted with cathepsins K, L, and S at 1:1 stoichiometry and with
      second-order rate constants >/= 1 x 10(5) M-1 s-1. These rate constants were
      comparable to those obtained with the prototypical physiological cysteine
      proteinase inhibitor, cystatin C. Also relative to cystatin C, SCCA1 was a more
      potent inhibitor of cathepsin K-mediated elastolytic activity by forming longer
      lived inhibitor-proteinase complexes. The t1/2 of SCCA1-cathepsin S complexes was
      >1155 min, whereas that of cystatin C-cathepsin complexes was 55 min. Cleavage
      between the Gly and Ser residues of the reactive site loop and detection of a
      stable SCCA1-cathepsin S complex by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis suggested that the serpin interacted with the cysteine proteinase
      in a manner similar to that observed for typical serpin-serine proteinase
      interactions. These data suggest that, contingent upon their reactive site loop
      sequences, mammalian serpins, in general, utilize their dynamic tertiary
      structure to trap proteinases from more than one mechanistic class and that
      SCCA1, in particular, may be involved in a novel inhibitory pathway aimed at
      regulating a powerful array of lysosomal cysteine proteinases.

PMID- 9548758
TI  - Role of zinc in the structure and toxic activity of botulinum neurotoxin.
AB  - Zn2+-protease activity of botulinum neurotoxin causes the blockage of
      neurotransmitter release resulting in botulism disease. We have investigated the
      role of Zn2+ in the biological activity of type A botulinum neurotoxin by
      removing the bound Zn2+ by EDTA treatment, followed by monitoring its structure
      in terms of secondary and tertiary folding (second derivative UV, FT-IR, and
      circular dichroism spectroscopy) and function in terms of its effect on the
      release of norepinephrine from PC12 cells. The single Zn2+ bound to each
      neurotoxin molecule was reversibly removed by EDTA treatment, whereas the
      biological activity of the neurotoxin was irreversibly lost. Based on the Amide
      III IR spectral analysis, the alpha-helical content of neurotoxin increased from
      29% to 42% upon removal of Zn2+, which reverted to 31% upon treatment with 1:5
      molar excess of exogenous Zn2+. Second derivative UV spectroscopy revealed no
      change in surface topography of Tyr residues with removal of Zn2+. However, near
      UV circular dichroism signals suggested significant alterations in the topography
      of Phe and Tyr residues that could be buried in the protein matrix. Thermal
      unfolding experiments suggested that removal of Zn2+ results in the formation of
      the molten globule-like structure of type A botulinum neurotoxin. Tertiary
      structural changes introduced by Zn2+ removal were irreversible, which correlated
      well with the irreversibility of the biological activity of the neurotoxin. On
      the basis of these results, we suggest that Zn2+ plays a significant structural
      role in addition to its catalytic role in Zn2+-protease activity of type A
      botulinum neurotoxin.

PMID- 9548759
TI  - Effect of ligand conformation on melanoma cell alpha3beta1 integrin-mediated
      signal transduction events: implications for a collagen structural modulation
      mechanism of tumor cell invasion.
AB  - The importance of three-dimensional interactions between receptors with their
      respective ligands has been extensively explored during the binding process, but
      considerably less so for postbinding events such as induction of signaling
      pathways. Tumor cell receptor association with basement membrane proteins is
      believed to facilitate the metastatic process. Melanoma and ovarian carcinoma
      cells have been shown to utilize the alpha3beta1 integrin to bind to models of
      the alpha1(IV)531-543 sequence from basement membrane (type IV) collagen [Miles,
      A. J., et al. (1994) J. Biol. Chem. 269, 30939-30945; Miles, A. J., et al. (1995)
      J. Biol. Chem. 270, 29047-29050]. In the present study, the effects of ligand
      three-dimensional structure on possible signal transduction pathways induced by
      alpha3beta1 integrin binding have been evaluated. Human melanoma cell binding to
      type IV collagen resulted in Tyr phosphorylation of p125(FAK), consistent with
      prior studies correlating beta1 integrin subunit binding to collagen and
      p125(FAK) Tyr phosphorylation. Cross-linking of an anti-alpha3 integrin subunit
      monoclonal antibody also induced p125(FAK) Tyr phosphorylation. Incubation of
      melanoma cells with single-stranded or triple-helical peptide models of
      alpha1(IV)531-543 induced Tyr phosphorylation of intracellular proteins.
      Immunoprecipitation analysis identified one of these proteins as pp125(FAK).
      Induction of p125(FAK) Tyr phosphorylation was enhanced and the time of induction
      was shortened when the ligand was used in triple-helical conformation. Subsequent
      clustering of either the single-stranded or the triple-helical ligand also
      increased the level of p125(FAK) phosphorylation compared to unclustered ligand.
      The clustered triple-helical peptide ligand induced more rapid paxillin Tyr
      phosphorylation than the single-stranded ligand. In addition, the induction of
      activated proteases was found to be more rapid due to ligand triple helicity.
      Overall, these studies have shown that (i) a model of an isolated sequence from
      type IV collagen, alpha1(IV)531-543, can induce alpha3beta1 integrin-mediated
      signal transduction in melanoma cells and (ii) ligand conformation (secondary,
      tertiary, and/or quaternary structure) can directly influence several alpha3beta1
      integrin-mediated signal transduction events. The effects of ligand conformation
      suggest that a "collagen structural modulation" mechanism may exist for tumor
      cell invasion, whereby triple-helical collagen promotes cell binding and
      induction of signal transduction, subsequently leading to collagen dissolution by
      proteases, decreased signal transduction, and enhanced tumor cell motility.

PMID- 9548760
TI  - Interaction of mant-adenosine nucleotides and magnesium with kinesin.
AB  - Displacement of the fluorescent substrate analogue methylanthraniloyl ADP (mant
      ADP) from kinesin by excess ATP results in a biphasic fluorescent transient. The
      pH and microtubule dependence of the rates and amplitudes indicates that the two
      phases are produced by release of bound mant-ADP, with an excess of the 3'
      isomer, followed by the subsequent relaxation of the free 2'- and 3'-isomers to
      their equilibrium distribution. The first phase for release of mant-ADP is
      accelerated by microtubules and occurs at the same rate as ADP release measured
      using [32P]ADP. The second phase is subject to base catalysis and occurs at the
      same rate as the isomerization of isolated 2'- or 3'-mant-ATP over a 100-fold
      range of rates. The bound mant-ADP isomers undergo isomerization rapidly when
      bound to kinesin at pH 8.2, whereas mant-ADP isomers interconvert only slowly
      when bound to myosin. No fluorescence resonance energy transfer occurs between
      the single tryptophan in the kinesin neck domain and bound mant-ADP, but
      efficient energy transfer does occur from protein tyrosine groups. The rate of
      mant-ADP release in the absence of microtubules is minimal (0.005 s-1) at pH 7-8,
      2 mM Mg2+, and 25 mM KCl but is accelerated at lower pH (0.04 s-1 at pH 5.5) and
      either lower or higher [KCl] (0.01 and 0. 06 s-1 at 0 and 800 mM KCl,
      respectively). The microtubule-stimulated rate of ADP release is accelerated at
      low pH and inhibited by high concentrations of monovalent salts. Reduction of the
      free Mg2+ by addition of excess EDTA increases the release of mant-ADP from
      E.MgADP to 0.03 s-1. This acceleration at low Mg2+ likely represents sequential
      release of Mg2+ at 0.03 s-1 followed by rapid release of ADP, as the rate of ADP
      release from Mg-free E.ADP is fast (>0.5 s-1). At high Mg2+, rebinding of Mg2+ to
      E.ADP forces release of ADP from the E.MgADP complex at 0.005 s-1.

PMID- 9548761
TI  - Glucosylation and ADP ribosylation of rho proteins: effects on nucleotide
      binding, GTPase activity, and effector coupling.
AB  - We studied the effects of glucosylation of RhoA, Rac1, and Cdc42 at threonine-35
      and -37 by Clostridium difficile toxin B on nucleotide binding, GTPase activity,
      and effector coupling and compared these results with the ADP ribosylation of
      RhoA at asparagine-41 catalyzed by Clostridium botulinum C3 transferase. Whereas
      glucosylation and ADP ribosylation had no major effects on GDP release from RhoA,
      Rac1, and Cdc42, the rate of GTPgammaS release from Rho proteins was increased 3
      6-fold by glucosylation. ADP ribosylation decreased the rate of GTPgammaS release
      by about 50%. Glucosylation reduced the intrinsic activities of the GTPases by 3
      7-fold and completely blocked GTPase stimulation by Rho-GAP. In contrast, ADP
      ribosylation slightly increased GTPase activity ( approximately 2-fold) and had
      no major effect on GAP stimulation of GTPase. Whereas ADP ribosylation did not
      affect the interaction of RhoA with the binding domain of protein kinase N,
      glucosylation inhibited this interaction. Glucosylation of Rac1 markedly
      diminished its ability to support the activation of the superoxide-generating
      NADPH oxidase of phagocytes. Glucosylated Rac1 did not interfere with NADPH
      oxidase activation by unmodified Rac1, even when present in marked molar excess,
      indicating that it was incapable of competing for a common effector. The data
      indicate that the functional inactivation of small GTPases by glucosylation is
      mainly caused by inhibition of GTPase-effector protein interaction.

PMID- 9548762
TI  - Probing catalytic hinge bending motions in thermolysin-like proteases by glycine 
      -> alanine mutations.
AB  - The active site of thermolysin-like proteases (TLPs) is located at the bottom of
      a cleft between the N- and C-terminal domains. Crystallographic studies have
      shown that the active-site cleft is more closed in ligand-binding TLPs than in
      ligand-free TLPs. Accordingly, it has been proposed that TLPs undergo a hinge
      bending motion during catalysis resulting in "closure" and "opening" of the
      active-site cleft. Two hinge regions have been proposed. One is located around a
      conserved glycine 78; the second involves residues 135 and 136. The importance of
      conserved glycine residues in these hinge regions was studied experimentally by
      analyzing the effects of Gly --> Ala mutations on catalytic activity. Eight such
      mutations were made in the TLP of Bacillus stearothermophilus (TLP-ste) and their
      effects on activity toward casein and various peptide substrates were determined.
      Only the Gly78Ala, Gly136Ala, and Gly135Ala + Gly136Ala mutants decreased
      catalytic activity significantly. These mutants displayed a reduction in kcat/Km
      for 3-(2-furylacryloyl)-L-glycyl-L-leucine amide of 73%, 62%, and 96%,
      respectively. Comparisons of effects on kcat/Km for various substrates with
      effects on the Ki for phosphoramidon suggested that the mutation at position 78
      primarily had an effect on substrate binding, whereas the mutations at positions
      135 and 136 primarily influence kcat. The apparent importance of conserved
      glycine residues in proposed hinge-bending regions for TLP activity supports the
      idea that hinge-bending is an essential part of catalysis.

PMID- 9548763
TI  - A single calcium binding site is crucial for the calcium-dependent thermal
      stability of thermolysin-like proteases.
AB  - Thermostable thermolysin-like proteases (TLPs), such as the TLP of Bacillus
      stearothermophilus CU-21 (TLP-ste), bind calcium in one double (Ca1,2) and two
      single (Ca3, Ca4) calcium binding sites. The single sites are absent in
      thermolabile TLPs, suggesting that they are determinants of (variation in) TLP
      stability. Mutations in the Ca3 and Ca4 sites of TLP-ste indeed reduced thermal
      stability, but only mutations in the Ca3 site affected the calcium-dependence of
      stability. The predominant effect of the Ca3 site results from the fact that the
      Ca3 site is part of a region of TLP-ste, which unfolding is crucial for thermal
      inactivation. Thermal inactivation is not caused by the absence of calcium from
      the Ca3 site per se, but rather by unfolding of a region of TLP-ste for which
      stability depends on the occupancy of the Ca3 site. In accordance with this
      concept is the observation that the effects of mutations in the Ca3 site could be
      compensated by stabilizing mutations near this site. In addition, it was observed
      that the contribution of calcium binding to the Ca3 was substantially reduced in
      extremely stable TLP-ste variants containing multiple stabilizing mutations in
      the Ca3 region. Apparently, in these latter variants, unfolding of the Ca3 region
      contributes little to the overall process of thermal inactivation.

PMID- 9548764
TI  - Equilibrium and kinetic unfolding properties of dimeric human glutathione
      transferase A1-1.
AB  - The equilibrium and kinetic unfolding properties of homodimeric class alpha
      glutathione transferase (hGST A1-1) were characterized. Urea-induced equilibrium
      unfolding data were consistent with a folded dimer/unfolded monomer transition.
      Unfolding kinetics were investigated, using stopped-flow fluorescence, as a
      function of denaturant concentration (3.5-8.9 M urea) and temperature (10-40
      degrees C). The unfolding pathway, monitored by tryptophan fluorescence, was
      biphasic with a fast unfolding event (millisecond time range with enhanced
      fluorescence properties) and a slow unfolding event (seconds to minutes time
      range with quenched fluorescence properties). Both events occurred simultaneously
      from 3.5 M urea. Each phase displayed single-exponential behavior, consistent
      with two unimolecular reactions. Urea-dependence studies and thermodynamic
      activation parameters (transition-state theory) suggest that the transition state
      for each phase is well-structured and is closely related to native protein in
      terms of solvent exposure. The apparent activation Gibbs free energy change in
      the absence of denaturant, DeltaG (H2O), indicates that the slow unfolding event
      represents the transition state for the overall unfolding pathway. The rate and
      urea independence of each phase on the initial condition exclude the possibility
      of a preexisting equilibrium between various native forms in the pretransition
      baseline. The unfolding pathways monitored by energy transfer to or direct
      excitation of AEDANS covalently linked to Cys111 in hGST A1-1 were monophasic
      with urea and temperature properties similar to those observed for the slow
      unfolding event (described above). A sequential unfolding kinetic mechanism
      involving the partial dissociation of the two structurally distinct domains per
      subunit followed by complete domain and subunit unfolding is proposed.

PMID- 9548765
TI  - Small-angle X-ray solution-scattering studies on ligand-induced subunit
      interactions of the thiamine diphosphate dependent enzyme pyruvate decarboxylase
      from different organisms.
AB  - The quaternary structures of the thiamine diphosphate dependent enzyme pyruvate
      decarboxylase (EC 4.1.1.1) from the recombinant wild type of
      Saccharomycescerevisiae and Zymomonas mobilis and from germinating Pisum sativum
      seeds were examined by X-ray solution scattering. The dependence of the subunit
      association equilibrium on the pH and the presence of the cofactors thiamine
      diphosphate and magnesium ions were compared, and the differences between the
      catalytic properties of the different enzymes are discussed. The influence of
      amino acid substitutions at the cofactor binding site of the enzyme from
      Saccharomyces cerevisiae (E51 is substituted by Q or A and G413 by W) on the
      subunit association was examined. Low-resolution models of the P. sativum,
      Z.mobilis, and S. cerevisiae enzymes were evaluated ab initio from the scattering
      data. The enzyme from the bacterium and yeast appear as a dimer of dimers,
      whereas the plant enzyme is an octamer formed by two tetramers arranged side-by
      side. The shape of the S. cerevisiae enzyme agrees well with the atomic structure
      in the crystal but suggests that the dimers in the latter should be tilted by
      approximately 10 degrees. The resulting modification of the atomic structure also
      yields a significantly better fit to the experimental solution scattering data
      than that calculated form the original crystallographic model.

PMID- 9548766
TI  - Probing the structure of the cytoplasmic domain of the aspartate receptor by
      targeted disulfide cross-linking 

PMID- 9548767
TI  - Anaerobic dechlorinating bacteria.
AB  - Anaerobic dehalogenation is attracting great interest since it opens new research
      horizons based on the novel biochemical mechanisms identified in this field such
      as halorespiration, i.e. the utilization of halogenated compounds as electron
      acceptors. Moreover, anaerobic bacteria seem to be more efficient than their
      aerobic counterparts in removing halogen atoms from polyhalogenated compounds.
      Thus, anaerobic dehalogenation can be considered as a promising means for
      bioremediation treatments of persistently polluted environments. In this line,
      identification of pure strains capable of dehalogenation will give important
      information about the diversity of organisms implicated in this process and also
      fundamental explanations of the diverse biochemical mechanisms involved. In light
      of these considerations, we chose to focus this review on the physiological
      descriptions, dechlorination activities, phylogenetic diversity, and potential
      biotechnological applications of these pure anaerobic strains capable of
      dehalogenation.

PMID- 9548768
TI  - Synthesis of bisected glycoforms of recombinant IFN-beta by overexpression of
      beta-1,4-N-acetylglucosaminyltransferase III in Chinese hamster ovary cells.
AB  - Genetic engineering of oligosaccharide biosynthesis pathways in mammalian cells
      makes possible generation of new recombinant glycoproteins of potential
      importance in the biopharmaceutical industry. Most prior investigations of
      glycosylation engineering of secreted heterologous glycoproteins involve terminal
      steps of oligosaccharide biosynthesis. In particular, increasing the frequency of
      bisected structures within the glycoform distribution has not before been
      considered. A Chinese hamster ovary (CHO) cell line capable of producing bisected
      oligosaccharides on glycoproteins was created by overexpression of a recombinant
      N-acetylglucosaminyltransferase III (GnT-III). Interferon beta (IFN-beta) was
      chosen as a model and potential therapeutic secreted heterologous protein to
      demonstrate the effect of recombinant GnT-III-expression on product
      glycosylation. IFN-beta with bisected oligosaccharides was produced by the GnT
      III-engineered CHO cells but not by the unmodified parental cell line.

PMID- 9548769
TI  - Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering.
AB  - Cell seeding of three-dimensional polymer scaffolds is the first step of the
      cultivation of engineered tissues in bioreactors. Seeding requirements of large
      scaffolds to make implants for potential clinical use include: (a) high yield, to
      maximize the utilization of donor cells, (b) high kinetic rate, to minimize the
      time in suspension for anchorage-dependent and shear-sensitive cells, and (c)
      high and spatially uniform distribution of attached cells, for rapid and uniform
      tissue regeneration. Highly porous, fibrous polyglycolic acid scaffolds, 5-10 mm
      in diameter and 2-5 mm thick, were seeded with bovine articular chondrocytes in
      well-mixed spinner flasks. Essentially, all cells attached throughout the
      scaffold volume within 1 day. Mixing promoted the formation of 20-32-micron
      diameter cell aggregates that enhanced the kinetics of cell attachment without
      compromising the uniformity of cell distribution. The kinetics and possible
      mechanisms of cell seeding were related to the formation of cell aggregates by a
      simple mathematical model that can be used to optimize seeding conditions for
      cartilage tissue engineering.

PMID- 9548770
TI  - Screening tool for hollow-fiber bioreactor process development 
AB  - Fundamental research of factors affecting cell growth in hollow-fiber bioreactors
      is hindered by the lack of an efficient screening tool. To address this issue, a
      hollow-fiber micro-bioreactor has been developed. Hollow fibers with 10 kDa
      molecular weight cutoffs are housed within a piece of silicone tubing. Cells are
      inoculated within the hollow fibers which provides a 0.2-mL culture volume. The
      space between the fibers and silicone tubing (5 or 16 mL) is used as a medium
      reservoir sufficient to feed the cells for at least 24 h. Oxygenation is provided
      directly through the silicone tubing so that a pump for medium recirculation is
      not required. As a result, many conditions can be tested simultaneously in a
      single incubator. Three days after inoculation at 5 x 10(6) cells/mL in the micro
      bioreactor, the rho 1D4 murine hybridoma cell line reached 2.8 x 10(7) cells/mL
      with an antibody concentration of 0.17 mg/mL. When inoculated at 5 x 10(7)
      cells/mL, the cell concentration reached 1.8 x 10(8)/mL after 3 days with an
      antibody concentration of 1.0 mg/mL. Results from a series of experiments with
      the micro-bioreactor suggested that the initial growth phase of this cell line in
      a hollow-fiber system is dependent on the serum concentration in the medium
      reservoir. This prediction was tested by simultaneously inoculating two
      production-scale hollow-fiber bioreactor systems. The cell side of the membrane
      for each bioreactor contained 10% serum, but serum was added to the reservoir
      side of only one of the bioreactors. The cells with only basal medium in the
      reservoir died after a few days, while the cells with 10% serum in the medium
      reservoir grew rapidly. These results demonstrate that the micro-bioreactor
      developed here can support good cell growth and that it can be used as a research
      tool to predict the performance of large-scale hollow-fiber systems.

PMID- 9548771
TI  - Heat-induced translocation of cytoplasmic beta-galactosidase across inner
      membrane of Escherichia coli.
AB  - The behaviors of heat-induced translocation of cytoplasmic beta-galactosidase to
      periplasm across the inner membrane of Escherichia coli cells were investigated
      in order to apply such phenomena to the process for production and separation of
      intracellular biomolecules. The heat stress was found to induce translocation of
      cytoplasmic beta-galactosidase (beta-gal) together with reduction of the amounts
      of intracellular soluble proteins and formation of their inactive aggregates. The
      translocation of beta-gal was then analyzed using (a) the location factor of beta
      gal (LFG), which meant enzyme location in the cells and could be determined from
      the kinetic analysis of enzyme release process, and (b) the percentage of beta
      gal activity in periplasm after solublizing the outer membrane of E. coli cells
      by lysozyme/EDTA treatment. The LFG values were maximized when cells were
      stressed at the temperature of 42-47 degrees C. From the results on the surface
      properties of both beta-gal and cell membrane under the heat stress, it is
      suggested that (1) the conformational change of cytoplasmic oligomeric beta-gal
      to the partially dissociated and/or unfolded state with higher local
      hydrophobicity, (2) the increase in membrane fluidity of inner membrane, (3) the
      enhancement of hydrophobic interaction between lipid and protein, and (4) the
      inhibition of its translocation by GroEL restabilizing the proteins could
      underlie the heat-induced translocation of beta-gal across the inner membrane.
      The possibility to apply the heat-induced translocation of beta-gal for the
      enhancement of the target selectivity at the process upstream is finally
      presented.

PMID- 9548773
TI  - Appearance of protease activities coincides with p10 and polyhedrin-driven
      protein production in the baculovirus expression system: effects on yield.
AB  - A study of proteolysis effects on recombinant protein yield was completed using
      the insect cell (Sf-9)-baculovirus (AcNPV) expression system. Activities of
      protease and beta-galactosidase (beta-gal), a marker heterologous protein, were
      assayed at various multiplicities of infection (MOI = 1, 5, and 20) on a time
      course postinfection. Also, several protein-substrate gel electrophoresis assays
      were run using gelatin, beta-gal, and bovine serum albumin (BSA) in the gel
      matrix, to determine the protein specificity of the proteases. The most abundant
      protease activity (cysteine), found at 49 kDa, degraded all three substrates, pre
      and post-infection. Two other protease activities (40 and 36 kDa) appeared on
      polyacrylamide gel electrophoresis (PAGE) gels after 72 hpi (hours
      postinfection). In addition, the culture with the highest MOI had the highest
      beta-gal activity until 72 hpi, when the activity dramatically decreased
      coincidentally with a 2.5-fold increase in protease activity. This result and the
      electrophoresis evidence that the protease is specific to beta-gal, indicate that
      there is a negative correlation between protease activity and recombinant protein
      yield. These results guide efforts to control product-degrading proteolysis in
      insect cell-baculovirus expression systems by harvest timing and the addition of
      protease inhibitors.

PMID- 9548772
TI  - Model system for heat-induced translocation of cytoplasmic beta-galactosidase
      across phospholipid bilayer membrane.
AB  - The possibility of the translocation of the enzyme across the phospholipid
      bilayer membrane was investigated by using the liposomes prepared by 1-palmitoyl
      2-oleoyl-sn-glycero-3-phosphocholine (POPC) in which beta-galactosidase (beta
      gal) was entrapped. Exposing the POPC liposomes entrapping beta-gal inside to
      heat treatment (40-50 degrees C, 1-60 min) was found to induce its translocation
      across the liposome membrane. The translocated activity of beta-gal from inner to
      outer aqueous phase of liposomes indicated the maximal value when the liposomes
      entrapping beta-gal were heated at 45 degrees C for 30 min. The gel permeation
      profiles of the liposomes before and after heat treatment (45 degrees C, 30 min)
      also supported the translocation of beta-gal across the liposome membrane. The
      membrane fluidity of liposomes was found to be increased with increasing
      temperature, so that the hydrophobicity of liposome membrane was also increased.
      The local hydrophobicity of beta-gal was maximized at the temperature of 40-50
      degrees C. The mechanisms of beta-gal translocation have been suggested to be
      triggered by the enhancement of hydrophobic interaction between the liposome
      surface and beta-gal molecules. Finally, a minimal scheme of possible mechanism
      on the heat-induced translocation of beta-gal has been presented on the basis of
      the hydrophobic interaction between the liposome and the proteins. The
      experimental data on the heat-induced translocation of beta-gal were well
      corresponding to those from model calculation.

PMID- 9548774
TI  - Influence of morphology on product formation in aspergillus awamori during
      submerged fermentations 
AB  - The relationship between fungal morphology and heterologous protein production
      was examined for an Aspergillus awamori strain during a series of fermentations
      with a batch phase followed by a fed-batch phase. Agitation rate and inoculation
      concentration were used as controlled variables to generate different fungal
      morphologies in 20-dm3 stirred tank reactors. Morphology was quantitatively
      characterized using Image Analysis. The different agitation rates and inoculum
      concentrations had large effects on the development in hyphal length and number
      of tips during the fermentations. A reduced inoculum concentration resulted in a
      more branched mycelium. The different agitation rates affected the morphology
      after 30 h of fermentation significantly but did not affect the start time of
      fragmentation. A 3-fold increase in hyphal length increased the apparent
      viscosity by a factor of 7. The observed morphological differences had only a
      limited effect on product formation, suggesting that the structural features such
      as hyphal length and number of tips are of less importance for product formation.
      The primary effect of morphology on product formation is due to viscosity.

PMID- 9548776
TI  - Computational fluid dynamics model for predicting flow of viscous fluids in a
      large fermentor with hydrofoil flow impellers and internal cooling coils 
AB  - Considerable debate has occurred over the use of hydrofoil impellers in large
      scale fermentors to improve mixing and mass transfer in highly viscous non
      Newtonian systems. Using a computational fluid dynamics software package (Fluent,
      version 4.30) extensive calculations were performed to study the effect of
      impeller speed (70-130 rpm), broth rheology (value of power law flow behavior
      index from 0.2 to 0.6), and distance between the cooling coil bank and the
      fermentor wall (6-18 in.) on flow near the perimeter of a large (75-m3) fermentor
      equipped with A315 impellers. A quadratic model utilizing the data was developed
      in an attempt to correlate the effect of A315 impeller speed, power law flow
      behavior index, and distance between the cooling coil bank and the fermentor wall
      on the average axial velocity in the coil bank-wall region. The results suggest
      that there is a potential for slow or stagnant flow in the coil bank-wall region
      which could result in poor oxygen and heat transfer for highly viscous
      fermentations. The results also indicate that there is the potential for slow or
      stagnant flow in the region between the top impeller and the gas headspace when
      flow through the coil bank-wall region is slow. Finally, a simple guideline was
      developed to allow fermentor design engineers to predict the degree of flow
      behind a bank of helical cooling coils in a large fermentor with hydrofoil flow
      impellers.

PMID- 9548775
TI  - Bacterial acid phosphatase gene fusions useful as targets for cloning-dependent
      insertional inactivation.
AB  - The Morganella morganii phoC gene, encoding a class A acid phosphatase, was used
      to generate gene fusions with modified amino-terminal moieties of the Escherichia
      coli lacZ gene carrying a multiple-cloning site flanked by phage-specific
      promoters and recognition sites for universal sequencing primers. The
      corresponding hybrid proteins retained a PhoC-like enzymatic activity which is
      easily detectable by a plate histochemical assay, rendering similar gene fusions
      potentially useful as targets for cloning-dependent insertional inactivation.
      Cloning experiments performed in plasmids carrying similar lacZ-phoC fusions
      confirmed their usefulness as cloning vectors for direct screening of
      recombinants. As compared to conventional lacZ alpha-complementation-based
      vectors, which can only be used in E. coli hosts carrying specific lacZ
      mutations, the lacZ-phoC fusion-based vectors can be used in combination with any
      E. coli host and require a less expensive histochemical assay for screening of
      recombinants, while retaining all the advantageous features that made the former
      so popular as general purpose cloning vehicles.

PMID- 9548777
TI  - Production of cell-free xanthan fermentation broth by cell adsorption on fibers 
AB  - Xanthan gum is a microbial polysaccharide widely used in food and oil-drilling
      industries. Xanthan gum produced from the current commercial fermentation process
      usually contains cells and cell debris, which lower the filterability of the
      xanthan solution and limit its applications. The production of cell-free xanthan
      gum fermentation broth is thus desirable. The feasibility of removing cells from
      the xanthan fermentation broth by cell adsorption to various woven fibrous
      materials was studied. It was found that both cotton and polyester fibers could
      be used to adsorb Xanthomonas campestris cells present in the fermentation broth
      either during batch fermentation or after the fermentation. Almost all cells were
      removed from the fermentation broth by adsorption to fibers. Cotton terry cloth
      had rough surfaces and was the preferred material for cell adsorption. Cell
      adsorption to cotton was faster than to polyester fibers. The adsorption kinetics
      can be modeled by a first-order rate equation. The adsorption rate constants were
      30-40% higher for cotton than for polyester. Cell adsorption was not efficient in
      the absence of xanthan gum, suggesting that the exopolysaccharide, xanthan gum,
      was important for efficient cell adsorption to fibers.

PMID- 9548778
TI  - Enhancing xanthan fermentations by different modes of glucose feeding 
AB  - This paper is the fourth in a series aimed at improving the understanding and
      operation of conventional agitated fermenters for the production of the
      commercially important gum, Xanthan. In the first, reproducible fermentations
      were established and this protocol was used in studies of different agitator
      types and of bulk mixing and dissolved oxygen concentration in the next two.
      Here, building on the previous work, the influence of different glucose feeding
      strategies on Xanthan production in a 20-L agitated fermenter under equivalent
      conditions of agitation and dissolved oxygen is reported. The biological
      performances in three types of fed-batch cultures (a two-step glucose addition,
      multiple glucose-pulse feeding and continuous feeding of glucose) are compared to
      two batch fermentations with different initial glucose concentrations. The work
      confirmed that improved performance cannot be achieved by increasing the initial
      glucose concentration above 50 g/L nor by a single 10 g/L pulse addition (initial
      glucose concentration of 40 g/L) while significant nitrogen is still present. On
      the other hand, the simple pulse and continuous feeding strategies, after
      nitrogen has been essentially exhausted and under conditions of nonlimiting
      dissolved oxygen and similar bulk mixing, can result in a greatly enhanced
      performance compared to batch fermentations. Using the final Xanthan gum
      concentration, the yield on glucose and the overall productivity as performance
      indices, values of 62 g/L, 0.82 g of Xanthan/g of glucose, and 0.72 g/(L.h),
      respectively, were obtained compared to literature values for conventional
      stirred bioreactors of 15-30 g/L, 0.27-0.86 g of Xanthan/g of glucose, and 0. 12
      0.43 g/(L.h).

PMID- 9548779
TI  - Production of 2-phenylethyl alcohol by Kluyveromyces marxianus.
AB  - Among the numerous yeasts able to produce flavor compounds, several strains of
      Kluyveromyces species are known for the synthesis of large amounts of aromatic
      compounds. In particular, the accumulation of 2-phenylethyl alcohol in liquid
      cultures of Kluyveromyces marxianus was observed after incubation on a
      semisynthetic medium at 30 degrees C, 125 rpm. Changes in the carbon sources led
      to a significant modification of the amount of this aromatic compound; moreover,
      the variations in the level of DL-phenylalanine and the exclusive use of a
      precursor isomer (L) also affected the synthesis of 2-phenylethyl alcohol.
      Finally, this study revealed the growth inhibition of K. marxianus when the
      concentration of 2-phenylethyl alcohol reached a critical value near 1.4 g/L; the
      use of an exponential model allowed the inhibition constant ki to be determined
      (ki = 0.35 g/L).

PMID- 9548780
TI  - Factors influencing parathion degradation by recombinant Escherichia coli with
      surface-expressed organophosphorus hydrolase.
AB  - A unique approach for organophosphorus pesticides detoxification was developed
      previously by anchoring organophosphorus hydrolase (OPH) onto the surface of
      Escherichia coli with a tightly regulated tac promoter. The resulting recombinant
      cells degraded parathion very effectively without the diffusional limitation
      observed in cells expressing OPH intracellularly. However, the precise conditions
      for surface targeting or pesticide degradation were not fully understood. In this
      paper, several factors influencing parathion degradation were investigated.
      Production of active OPH onto the cell surface was highly host-specific; a high
      rate of parathion degradation was observed from strains JM105 and XL1-Blue, which
      regulated production of the OPH fusion very tightly. However, in the absence of
      ampicillin selection, plasmids were only favorably maintained in strain XL1-Blue.
      OPH activity was highly dependent on growth conditions. Optimal OPH activity was
      observed when cells were grown in Luria-Bertani (LB)-buffered medium at 37
      degrees C. OPH activity was further improved by supplementing the growth medium
      with cobalt chloride, which favors the formation of the metal active center. The
      timing of cobalt addition also influenced parathion degradation. Maximum OPH
      activity was obtained by adding cobalt to induced cultures during the late
      stationary phase. The resulting cultures grown under the optimized conditions had
      an eight-fold increase in parathion degradation.

PMID- 9548781
TI  - Effect of cell morphology on dead-end filtration of the dimorphic yeast
      Kluyveromyces marxianus var. marxianus NRRLy2415.
AB  - The dead-end filtration characteristics of the dimorphic yeast Kluyveromyces
      marxianus var. marxianus (formerly fragilis) NRRLy2415 were investigated for a
      range of mean cell morphologies, ranging from predominantly yeast-like to
      predominantly filamentous. Semiautomated image analysis was used to measure the
      mean cell specific surface area, Sv, and the mean ratio of cell length to
      equivalent cylindrical diameter, Ldm, in each broth. The method of Ju and Ho
      (Biotechnol. Bioeng. 1988, 32, 95-99) was used to show that for broths with Ldm
      values between 1.72 and 10.03, the voidage of cell pellets formed by
      centrifugation increased with increasing Ldm. In the pressure range 30-180 kPa,
      the specific filter cake resistance, alpha, was found to be related to pressure,
      DeltaP, through the equation alpha = alpha0(1 + kcDeltaP). The dependence of
      alpha0/Sv2 on Ldm was found to be qualitatively consistent with the pellet
      voidage data and the Carman-Kozeny equation. Considerably better agreement with
      the experimental data was obtained when the Kozeny constant, K, was treated as
      variable and related to Ldm through the equation K = 4.83 + 7.08 log10 Ldm. The
      cake compressibility constant, kc, was found to increase with increasing Ldm, a
      phenomenon consistent with the wide range of voidages that can be displayed by
      beds of long cylinders.

PMID- 9548782
TI  - Optimization considerations for the purification of alpha1-antitrypsin using
      silica-based ion-exchange adsorbents in packed and expanded beds.
AB  - The influences of the fluid superficial velocity, sample concentration, loading
      volume, and wash cycle on the recovery and corresponding purification factors for
      alpha1-antitrypsin [syn. alpha1-proteinase inhibitor (alpha1-PI)] from crude
      mixtures of human plasma proteins were investigated using packed and expanded
      beds of DEAE-Spherodex LS. As part of this study, the effect of fluid superficial
      velocity on the bed dispersion number (Dv) and dispersion coefficient (D) for
      this adsorbent in expanded beds was determined with feedstocks containing human
      serum albumin (HSA), the most abundant of the contaminating proteins in human
      plasma protein preparations used for the isolation of alpha1-PI. When
      multicomponent protein feedstocks prepared from human plasma were examined with
      DEAE-Spherodex LS, reduced chromatographic productivity was observed for alpha1
      PI as the extent of column utilization and the superficial velocity were
      increased, yet the opposite trend was evident for HSA. In particular, higher
      adsorption capacities and recoveries were obtained for alpha1-PI at lower fluid
      superficial velocities with both packed and expanded bed conditions. These
      findings indicate that for process scale purifications of alpha1-PI from
      multicomponent feedstocks with expanded beds containing this silica-based ion
      exchange adsorbent, the optimal range of superficial velocities to achieve the
      highest bed productivity will not be synonymous with maximally fluidized modes of
      operation. Rather, the results confirm that the adsorbent has an optimum
      operational performance when fluidization procedures corresponding to plug flow
      expansion are employed for the capture of alpha1-PI. These findings also indicate
      that advantage can be taken of displacement effects between closely related
      protein species with packed and expanded bed systems containing the DEAE
      Spherodex LS type of ion-exchange porous silicas.

PMID- 9548783
TI  - Purification of alcohol dehydrogenase from four genotypes of the olive fruit fly
      Bactrocera (Dacus) oleae.
AB  - This is the first report describing the purification of alcohol dehydrogenase
      (ADH) from four genotypes of the olive fruit fly Bactrocera oleae, the most
      important pest of olives in the Mediterranean region. The purified enzyme shows a
      single band after SDS-PAGE analysis, corresponding to subunit mass of 26 kDa. The
      native ADH shows a molecular mass of 48 kDa, after gel filtration HPLC analysis.
      The purification method incorporated a preliminary ammonium sulphate
      precipitation step, followed by an anion-exchange DEAE chromatography step, a dye
      affinity chromatography step on Cibacron blue 3GA, and an anion-exchange DEAE
      chromatography step employing the same column of the first step. The present
      method offers good overall recovery (40%) and high enzyme purity, and it is
      applicable to different genotypes. Furthermore, the method is rapid and
      economical, as it employs two cheap, widely used, and commercially available
      chromatography materials.

PMID- 9548784
TI  - Protein focusing in a conductivity gradient.
AB  - Conductivity gradient focusing (CGF) is one member of a family of gradient
      focusing techniques, characterized by two opposing forces which produce a dynamic
      equilibrium and which are able to simultaneously separate and concentrate
      proteins. In CGF, the two counteracting forces result from a constant convective
      flow of buffer opposed by an electric field gradient. This gradient in the
      electric field is formed by gradually decreasing buffer conductivity, i.e., when
      a slow-moving, relatively high conductivity buffer is dialyzed against a low
      conductivity purge buffer. This paper presents the design of an analytical-scale
      CGF device and the results of several experiments with colored proteins, both in
      free solution and with the use of a 45 micron size-exclusion (SEC) packing to
      decrease dispersion. Experimental results with hemoglobin suggest that CGF may
      one day be capable of resolving proteins with small charge differences. A linear
      computer model of conductivity gradient focusing is derived, and some suggestions
      are made for further development of this new electrophoretic method.

PMID- 9548785
TI  - Preparation and characterization of bifunctional biopolymers for receptor-based
      liposomal immunosensing.
AB  - In this study, we prepared bifunctional biopolymers for development of a novel
      liposomal immunosensing element. These biopolymers were produced such that a rat
      monoclonal antibody fragment Fab' was linked to a cardiac protein Troponin I
      (TnI) peptide by a cross-linking reagent, o-phenylenedimaleimide (o-PDM) or N
      sucinimidyl 3-(2-pyridyldithio)propionate (SPDP). The biopolymer formation yields
      were approximately 10% for Fab-TnIMal and 30% for Fab-TnISPDP. Molar ratios of
      Fab' to SPDP or o-PDM and conjugated Fab' to TnI peptide and conjugation pH have
      considerable effects on the biopolymer yield. Purification of these biopolymers
      was achieved by employing size-exclusion HPLC. These biopolymers can bind to
      receptor channels on one end, while the peptide end can be recognized by an anti
      TnI antibody serving as a protein linker to block the channels in the
      immunosensing element. Then reactions may be used where free analyte competes for
      cross-linker binding sites whereby channels are rendered active. Characterization
      of purified biopolymers was performed using gel electrophoresis, ELISAs, and a
      BIAcore instrument. Furthermore, results of real-time biospecific interaction
      experiments with use of the BIAcore show that competition binding reactions of
      free TnI peptide occurred in this new immunosensing design. The binding
      activities of these two biopolymers are slightly different.

PMID- 9548786
TI  - Correlation of fermentation yield with yeast extract composition as characterized
      by near-infrared spectroscopy 
AB  - Complex, ill-defined mixtures of natural origin are often used as nutrients in
      the production of biological products through microbial fermentation. Product
      yields are affected by variation in these natural products. It was desired to
      examine near-infrared spectroscopy as a rapid screening tool for qualifying raw
      material lots. Specifically, the characterization of yeast extract was
      investigated. The model system consisted of a Merck & Co., Inc., microbial
      fermentation process. Cell mass and specific product yields are dependent upon
      variations in the yeast extract used in the medium. Partial least-squares
      regression on the second-derivative spectral absorbances of various yeast
      extracts in the ranges 1150-1380, 1554-1826, and 2100-2300 nm resulted in the
      development of models with multiple correlation coefficients of 0.99 for cell
      mass yields and 0.96 for specific product yields in large-scale fermentations.
      These models could also be used to predict cell mass yields in 15 L batch
      fermentations and specific product yields in 2-L shake flasks.

PMID- 9548787
TI  - Steam-sterilizable, fluorescence lifetime-based sensing film for dissolved carbon
      dioxide.
AB  - An autoclavable sensing film was developed for monitoring dissolved CO2. The
      sensing film, based on fluorescence resonance energy transfer (FRET), consisted
      of a fluorescent donor, an acceptor, and a quaternary ammonium hydroxide, which
      were doped in a two-component silicone film. As no aqueous solution was used in
      the sensing film matrix, the sensing film was unaffected by osmotic pressure.
      Fluorescence lifetime was selected as the sensing parameter, and measured in
      frequency domain using phase fluorometry. Upon exposure to 20% CO2-saturated
      water, a 43 degrees increase in phase angle was observed at 100 MHz. The process
      was fully reversible when the sensing film was exposed to nitrogen-saturated
      water. The estimated response and recovery times for 90% signal change were 1 min
      (for a step change from 0 to 6.7% CO2-saturated water) and 1.5 min (for a step
      change from 6.7 to 3.3% CO2-saturated water). When used for on-line monitoring of
      dissolved CO2 produced by a culture of Escherichia coli, the sensing film showed
      a similar trend to that obtained from off-line measurements using a wet chemistry
      analyzer.

PMID- 9548788
TI  - Purification of antibodies from protein mixtures and mouse ascites fluid using
      Zeolite X.
AB  - Zeolite A and calcium phosphate modified Zeolite A have been shown to be a new
      effective packing material in ion exchange chromatography for the purification of
      immunoglobulin G (IgG) from binary mixtures and mouse ascites fluid. This study
      was to determine the effectiveness of purifying IgG using Zeolite X and
      dealuminated Zeolite X with twice the pore size of Zeolite A. Binary mixtures
      (IgG-albumin and IgG-transferrin) and a mouse ascites fluid were purified in
      Zeolite X (in Na+, K+, or NH4+ form) chromatographic columns and with
      dealuminated Zeolite X under a variety of operational conditions. The biological
      activity of the purified IgG from the mouse ascites fluid was confirmed by ELISA.
      The characteristics of zeolites in the present study suggest that functional
      groups of a protein displace the cations of zeolites near the crystal surfaces
      and create a different strength of affinity. The study demonstrated that Zeolite
      X and dealuminated Zeolite X are also promising new packing materials for the
      purification of IgG from biological materials.

PMID- 9548789
TI  - Effects of secondary flow caused by a curved channel on plasma protein adsorption
      to artificial surfaces.
AB  - The effects of secondary flow induced by a curved channel on fibrinogen
      deposition and replacement on a glass surface were studied. Platelet adhesion to
      surface-bound fibrinogen was also studied to indicate how secondary flow may
      affect thrombogenesis on artificial surfaces. A saline pre-wetted channel with
      straight and curved sections was exposed to flowing plasma at a Reynolds number
      of 28.6. Results show that fibrinogen deposited on the surface at a shear rate of
      175 s-1 was replaced faster in regions of secondary flow (Dean numbers from 11 to
      19) than in adjacent regions of shear flow. Platelets adhered only to those
      surfaces where fibrinogen had been detected.

PMID- 9548790
TI  - Recovery and reuse of the molecular chaperone GroEL for in vitro protein
      refolding.
AB  - The chaperones GroEL and GroES from Escherichia coli are known to improve in
      vitro protein refolding yields. We show that, for the molecular chaperone
      assisted refolding of hen egg white lysozyme, GroES is not an essential
      requirement and that activity is recovered with GroEL and ATP alone. The
      refolding yields of lysozyme in the presence of GroEL are much greater than those
      obtained by dilution because of a reduction in protein aggregation. On the basis
      of the large difference in molecular weight between the GroEL complex (MW 840
      000) and lysozyme (MW 14 600), we have demonstrated that using an ultrafiltration
      membrane (MW 30 000) GroEL may be easily retained after refolding while lysozyme
      passes freely into the permeate. The chaperonin recovered from the refolding
      solution was then reused several times for further refolding experiments. The
      effectiveness of GroEL-assisted refolding was found to decrease with reuse, and
      this has been attributed to a reduction in the GroEL:lysozyme molar ratio.

PMID- 9548791
TI  - Crystallization and X-ray diffraction of crystals formed in water-plasticized
      amorphous lactose.
AB  - Effects of storage time and relative humidity on crystallization and crystal
      forms produced from amorphous lactose were investigated. Crystallization was
      observed from time-dependent loss of sorbed water and increasing intensities of
      peaks in X-ray diffraction patterns. The rate of crystallization increased with
      increasing storage relative humidity. Lactose crystallized mainly as alpha
      lactose monohydrate and anhydrous crystals with alpha- and beta-lactose in a
      molar ratio of 5:3. The results suggested that the crystal form was defined by
      the early nucleation process. The crystallization data are important in modeling
      of crystallization phenomena and prediction of stability of lactose-containing
      food and pharmaceutical materials.

PMID- 9548792
TI  - Green fluorescent protein as a real time quantitative reporter of heterologous
      protein production.
AB  - Since its cloning and commercial availability, applications of green fluorescent
      protein (GFP) as a reporter gene have become prevalent in many aspects of
      science. The attributes of GFP could also be applied to the area of heterologous
      protein production. The work described here represents the first experiments to
      use GFP as a generic tool to monitor protein production in bioprocess
      development. We have constructed a plasmid containing an operon fusion of the two
      reporter genes GFP and chloramphenicol acetyl transferase (CAT). CAT served as a
      "model" recombinant protein product to demonstrate the in situ quantifiable
      reporting mechanism of GFP. Our results indicate there is a direct correlation
      between the fluorescence intensity of GFP and the functional activity of the
      downstream CAT protein. In addition, there is a quantitative relationship between
      the level of CAT protein concentration and GFP fluorescence. These experiments
      provide the groundwork for using GFP as an in situ reporter gene for scale-up and
      process optimization of recombinant protein production.

PMID- 9548793
TI  - Free radical formation in the peroxynitrous acid (ONOOH)/peroxynitrite (ONOO-)
      system.
AB  - The rate constant of homolysis of peroxynitrite, ONOO-, into O2- and NO was
      determined to be 0.017 s-1 at 20 degrees C. In combination with other
      experimental data taken from the literature, this value yields the Gibbs free
      energy of formation of ONOO-, delta f G o(ONOO-) = 16.6 kcal/mol. On the basis of
      this result, we conclude that peroxynitrous acid homolyzes to yield nitrogen
      dioxide (NO2) and hydroxyl (OH) free radicals and derive delta f G o(ONOOH) = 7.7
      kcal/mol. The rate constant of the reaction between NO and ONOO- was found to be
      5 x 10(-)2 M-1 s-1 at most. The implications of the two homolysis reactions are
      discussed.

PMID- 9548794
TI  - Structural characterization of a 4-hydroxy-2-alkenal-derived fluorophore that
      contributes to lipoperoxidation-dependent protein cross-linking in aging and
      degenerative disease.
AB  - Modification of proteins by products of lipid peroxidation results in various
      fluorescent adducts associated with oxidative stress pathophysiology in
      degenerative disease. Using n-butylamine as a model for the lysine side chain,
      the structure of the probable major ex/em 360/430-nm fluorophore that arises from
      cross-linking of two protein-based lysines by one 4-hydroxy-2-alkenal is shown to
      be a 2-alkyl-2-hydroxy-1,2-dihydropyrrol-3-one iminium. That this fluorophore can
      be independently generated in higher yield from either 4-oxo-2-alkenals or 3,4
      dioxoalkanals supports a proposed mechanistic pathway that involves two 2e
      oxidations following initial Schiff base formation.

PMID- 9548795
TI  - Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit
      juice.
AB  - Grapefruit juice has been found to significantly increase oral bioavailability of
      several drugs metabolized by cytochrome P450 3A4 (P450 3A4) through inhibiting
      the enzymatic activity and decreasing the content of intestinal P450 3A4.
      HPLC/MS/MS and HPLC/UV analyses of ethyl acetate extracts from grapefruit juice
      revealed the presence of several furanocoumarins of which bergamottin (BG) is the
      major one. BG was shown to inactivate P450 3A4 in a reconstituted system
      consisting of purified P450 3A4, NADPH-cytochrome P450 reductase, cytochrome b5,
      and phospholipids. Inactivation was time- and concentration-dependent and
      required metabolism of BG. The loss of catalytic activity exhibited pseudo-first
      order kinetics. The values of kinactivation and KI calculated from the
      inactivation studies were 0.3 min-1 and 7.7 microM, respectively. While
      approximately 70% of the erythromycin N-demethylation activity was lost during
      incubation with BG in the reconstituted system, P450 3A4 retained more than 90%
      of the heme as determined either by UV-visible spectroscopy or by HPLC. However,
      approximately 50% of the apoP450 in the BG-inactivated P450 3A4 incubation
      mixture could not be recovered from a reverse-phase HPLC column when compared
      with the -NADPH control. The mechanism of the inactivation appears to involve
      modification of the apoP450 in the active site of the enzyme instead of heme
      adduct formation or heme fragmentation. These results indicate that BG, the
      primary furanocoumarin extracted from grapefruit juice, is a mechanism-based
      inactivator of P450 3A4. BG was also found to inhibit the activities of P450s
      1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes.

PMID- 9548796
TI  - Nuclear magnetic resonance spectroscopic and principal components analysis
      investigations into biochemical effects of three model hepatotoxins.
AB  - 1H NMR spectroscopy of urine combined with pattern recognition (PR) methods of
      data analysis has been used to investigate the time-related biochemical changes
      induced in Sprague-Dawley rats by three model hepatotoxins: alpha-naphthyl
      isothiocyanate (ANIT), d-(+)-galactosamine (GalN), and butylated hydroxytoluene
      (BHT). The development of hepatic lesions was monitored by conventional plasma
      analysis and liver histopathology. Urine was collected continuously postdosing up
      to 144 h and analyzed by 600-MHz 1H NMR spectroscopy. NMR spectra of the urine
      samples showed a number of time-dependent perturbations of endogenous metabolite
      levels that were characteristic for each hepatotoxin. Biochemical changes common
      to all three hepatotoxins included a reduction in the urinary excretion of
      citrate and 2-oxoglutarate and an increased excretion of taurine and creatine.
      Increased urinary excretion of betaine, urocanic acid, tyrosine, threonine, and
      glutamate was characteristic of GalN toxicity. Both GalN and ANIT caused
      increased urinary excretion of bile acids, while glycosuria was evident in BHT-
      and ANIT-treated rats. Data reduction of the NMR spectra into 256 integrated
      regions was used to further analyze the data. Mean values of each integrated
      region were analyzed by principal components analysis (PCA). Each toxin gave a
      unique time-related metabolic trajectory that could be visualized in two
      dimensional PCA maps and in which the maximum distance from the control point
      corresponded to the time of greatest cellular injury (confirmed by conventional
      toxicological tests). Thereafter, the metabolic trajectories changed direction
      and moved back toward the control region of the PR map during the postdose
      recovery phase. The combination of urinary metabolites which were significantly
      altered at various time points allowed for differentiation between biliary and
      parenchymal injury. This NMR-PR approach to the noninvasive detection of liver
      lesions will be of value in furthering the understanding of hepatotoxic
      mechanisms and assisting in the discovery of novel biomarkers of hepatotoxicity.

PMID- 9548797
TI  - Inorganic and methylated arsenic compounds induce cell death in murine
      macrophages via different mechanisms.
AB  - We demonstrate in this study the cytotoxic effects of inorganic arsenicals,
      arsenite and arsenate, and organic arsenic compounds, monomethylarsonic acid
      (MAA), dimethylarsinic acid (DMAA), and trimethylarsine oxide (TMAO), which are
      metabolites of inorganic arsenicals in human bodies, using murine macrophages in
      vitro. Inorganic arsenicals, both arsenite and arsenate, are strongly toxic to
      macrophages, and the concentration that decreased the number of surviving cells
      to 50% of that in untreated controls (IC50) was 5 or 500 microM, respectively.
      These inorganic arsenicals mainly caused necrotic cell death with partially
      apoptotic cell death; about 80% of dead cells were necrotic, and 20% were
      apoptotic. The inorganic arsenicals also induced marked release of an
      inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), at cytotoxic
      doses. This strong cytotoxicity of an inorganic arsenical, arsenite, might be
      mediated via active oxygen and protease activation because it was inhibited by
      the addition of some antioxidant reagents, such as superoxide dismutase (SOD),
      catalase, and GSH, or by a peptide inhibitor of interleukin-1 beta-converting
      enzyme (ICE). It is likely that these immunotoxic effects of inorganic arsenicals
      may evoke both immunosuppression and inflammation, and they may be central
      factors causing carcinogenesis and severe inflammatory responses, such as
      hepatomegaly and splenomegaly, in chronic arsenicosis patients who daily ingested
      arsenic-contaminated well water. In contrast, the cytotoxic effects of methylated
      arsenic compounds were lower than those of inorganic arsenicals. The IC50 value
      of DMAA was about 5 mM, and MAA and TMAO had no toxicity even at concentrations
      over 10 mM. Additionally, these methylated chemicals suppressed the TNFalpha
      release from macrophages. DMAA induced mainly apoptotic cell death in macrophages
      as indicated by cellular morphological changes, condensed nuclei, terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and
      DNA fragmentation. However, the cytotoxicity of DMAA might be induced via a
      different mechanism from that of inorganic arsenicals because it was not
      abolished by the additions of SOD, catalase, or ICE inhibitor. Conversely, GSH
      enhanced the toxicity of DMAA. These data suggest that methylation of inorganic
      arsenicals in mammals plays an important role in suppression of both severe
      immunosuppression and inflammatory responses caused by inorganic arsenicals.

PMID- 9548798
TI  - Structures of acrolein-guanine adducts: a semi-empirical self-consistent field
      and nuclear magnetic resonance spectral study.
AB  - The structures and conformations of adducts formed by reaction of guanosine with
      several mutagenic alpha,beta-unsaturated carbonyl compounds have been
      investigated by semi-empirical molecular orbital calculations and compared with
      NMR spectral results. Two cyclization processes taking place on the pyrimidine
      ring of guanine leading to two sets of regioisomers, 11-hydroxy- and 13
      hydroxytetrahydropyrimidinoguanines (THPG), were considered. Relative stabilities
      and geometries of all configurations and conformations of adducts with acrolein,
      crotonaldehyde, and alpha-chloroacrolein were calculated by PM3, AM1, and MNDO
      methods. PM3 results were the most compatible with experimental structures based
      on 400-MHz 1H NMR spectroscopy. The most stable structures for the 11-hydroxy and
      13-hydroxy THPG isomers from acrolein are predicted to have chair-like structures
      for the tetrahydropyrimidine ring and axial hydroxyl groups, as suggested by the
      NMR spectra of the isolated adducts. Of the possible isomers from guanine and
      crotonaldehyde, cis-11-hydroxy-13-methyl THPG with methyl and hydroxyl groups
      axial is predicted to be the most stable. The only isolated adduct is the trans
      13-hydroxy-11-methyl THPG with methyl shown to be equatorial and hydroxyl axial
      by 1H NMR. This is completely consistent with the geometry predicted by PM3 for
      the 13-hydroxy regioisomer of crotonaldehyde. In the case of adducts of alpha
      chloroacrolein, one stereoisomer predominates for each of the two possible
      regioisomers. For the 12-chloro-11-hydroxy isomer, the cis configuration with
      chlorine axial and hydroxyl quasi-axial is calculated to have the most stable
      geometry. In contrast, the 1H NMR spectrum supports a trans diaxial orientation,
      although the cis computed structure could also be accommodated by the spectrum.
      The 12-chloro-13-hydroxy regioisomer is unambiguously assigned as trans diaxial
      by PM3 calculations and 1H NMR spectroscopy.

PMID- 9548799
TI  - Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol
      metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and
      2A6.
AB  - Acetaminophen (APAP), a widely used analgesic and antipyretic agent, is
      bioactivated by cytochromes P450 to cause severe hepatotoxicity. APAP is oxidized
      by two pathways to form a toxic intermediate, N-acetyl-p-benzoquinone imine
      (NAPQI), and a nontoxic catechol metabolite, 3-hydroxy-APAP (3-OH-APAP). We
      investigated the role of P450 2E1 and 2A6 in APAP oxidation by using baculovirus
      expressed and highly purified forms of human P450 2E1 and 2A6. An electrochemical
      HPLC assay was developed to quantify both oxidative metabolites simultaneously.
      For the first time, it was demonstrated that human P450 2E1 selectively oxidized
      APAP to NAPQI (assayed as its glutathione conjugate, GS-APAP), whereas human P450
      2A6 selectively oxidized APAP to 3-OH-APAP. At 1 mM APAP, the relative ratio for
      the formation of GS-APAP vs 3-OH-APAP with human P450 2E1 was approximately 6:1,
      whereas the ratio with human P450 2A6 was 1:3. Apparent Km and Vmax values for
      the formation of GS-APAP by human P450 2E1 were 1.3 mM and 6.9 nmol/min/nmol of
      P450, respectively, whereas they were 4.6 mM and 7.9 nmol/min/nmol of P450 for
      P450 2A6. Apparent Km and Vmax values for the formation of 3-OH-APAP by human
      P450 2E1 were 4.0 mM and 2.5 nmol/min/nmol of P450, respectively, whereas they
      were 2.2 mM and 14.2 nmol/min/nmol of P450, respectively, for P450 2A6. Thus,
      although at toxic doses of APAP P450 2E1 is the more efficient catalyst for the
      formation of the toxic metabolite NAPQI, P450 2A6 also can contribute
      significantly to NAPQI production.

PMID- 9548800
TI  - Formation of hemoglobin and albumin adducts of benzene oxide in mouse, rat, and
      human blood.
AB  - Little is known about the formation and disposition of benzene oxide (BO), the
      initial metabolite arising from oxidation of benzene by cytochrome P450. In this
      study, reactions of BO with hemoglobin (Hb) and albumin (Alb) were investigated
      in blood from B6C3F1 mice, F344 rats, and humans in vitro. The estimated half
      lives of BO in blood were 6.6 min (mice), 7.9 min (rats), and 7.2 min (humans).
      The following second-order rate constants were estimated for reactions between BO
      and cysteinyl residues of Hb and Alb [in units of L (g of Hb- or Alb-h)-1]: mouse
      Hb = 1.16 x 10(-)4, rat Hb = 15.4 x 10(-)4, human Hb = 0.177 x 10(-)4, mouse Alb
      = 2.68 x 10(-)4, rat Alb = 4.96 x 10(-)4, and human Alb = 5.19 x 10(-)4. These
      rate constants were used with BO-adduct measurements to assess the systemic doses
      of BO arising from benzene in vivo in published animal and human studies. Among
      rats receiving a single gavage dose of 400 mg of benzene/kg of body weight, the
      BO dose of 2.62 x 10(3) nM BO-h, predicted from Alb adducts, was quite similar to
      the reported AUC0-infinity = 1.09 x 10(3) nM BO-h of BO in blood. Interestingly,
      assays of Hb adducts in the same rats predicted a much higher dose of 14.7 x
      10(3) nM BO-h, suggesting possible in situ generation of adducts within the
      erythrocyte. Doses of BO predicted from Alb adducts were similar in workers
      exposed to benzene [13.3 nM BO-h (mg of benzene/kg of body weight)-1] and in rats
      following a single gavage dose of benzene [8. 42 nM BO-h (mg of benzene/kg of
      body weight)-1]. Additional experiments indicated that crude isolates of Hb and
      Alb had significantly higher levels of BO adducts than dialyzed proteins,
      suggesting that conjugates of low-molecular-weight species were abundant in these
      isolates.

PMID- 9548801
TI  - Polymerase blockage and misincorporation of dNTPs opposite the ethylene dibromide
      derived DNA adducts S-[2-(N7-guanyl)ethyl]glutathione, S-[2-(N2
      guanyl)ethyl]glutathione, and S-[2-(O6-guanyl)ethyl]glutathione.
AB  - The carcinogen ethylene dibromide (EDB) has been shown to cause glutathione (GSH)
      dependent base-substitution mutations, especially GC to AT transitions, in a
      variety of bacterial and eukaryotic systems. The known DNA adducts S-[2-(N7
      guanyl)ethyl]GSH, S-[2-(N2-guanyl)ethyl]GSH, and S-[2-(O6-guanyl)ethyl]GSH were
      individually placed at a site in a single oligonucleotide. Polymerase extension
      studies were carried out using Escherichia coli polymerase I exo- (Klenow
      fragment, Kf-) and polymerase II exo- (pol II-), bacteriophage T7 polymerase exo
      , and human immunodeficiency virus-1 reverse transcriptase in order to
      characterize misincorporation events. Even though extension was not as efficient
      as with the nonadducted template, some fully extended primers were observed with
      the template containing S-[2-(N7-guanyl)ethyl]GSH using all of these polymerases.
      dCTP was the most preferred nucleotide incorporated opposite S-[2-(N7
      guanyl)ethyl]GSH by most of polymerases examined; however, dTTP incorporation was
      observed opposite S-[2-(N7-guanyl)ethyl]GSH with pol II-. Both S-[2-(N2
      guanyl)ethyl]GSH and S-[2-(O6-guanyl)ethyl]GSH strongly blocked replication by
      all polymerases. Only dATP and dGTP were incorporated opposite S-[2-(N2
      guanyl)ethyl]GSH by both Kf- and pol II-. S-[2-(O6-Guanyl)ethyl]GSH was shown to
      strongly code for dATP incorporation by Kf-. With pol II-, dTTP was incorporated
      opposite S-[2-(O6-guanyl)ethyl]GSH. In conclusion, all three GSH-guanyl adducts
      derived from the carcinogen EDB blocked the polymerases and were capable of
      miscoding.

PMID- 9548802
TI  - Reactions of 4-hydroxy-2(E)-nonenal and related aldehydes with proteins studied
      by carbon-13 nuclear magnetic resonance spectroscopy.
AB  - In order to understand the modifications of proteins produced by aldehydes of
      lipid peroxidation, [1-13C]-2(E)-hexenal, [1-13C]-4-oxopentanal, and a mixture of
      [1-13C]- and [2-13C]-4-hydroxynon-2(E)-enal were synthesized and the reaction of
      each of the labeled aldehydes with bovine serum albumin was analyzed by 13C NMR
      spectroscopy. Protein nucleophiles add to the 3-position of hexenal, and the
      resulting propanal moieties appear to undergo aldol condensation, form imine
      cross-links with lysyl residues, or lead to pyridinium rings. During the reaction
      of 4-oxopentanal with the lysyl residues of bovine serum albumin, only 1-alkyl-2
      methylpyrrole and a possible intermediate leading to the pyrrole were observed.
      Hydroxypyrrolidine cross-links such as 25 could not be detected, leaving the
      pyrrole as the mediator of protein cross-linking. The Michael adducts are the
      major products in the reaction between 4-hydroxynon-2-enal and proteins. They
      exist almost exclusively in the cyclic hemiacetal form and do not appear to cross
      link through imine formation with lysyl residues. A minor pathway involves the
      reaction of 4-hydroxynon-2-enal with the lysyl amino groups of protein resulting
      in 2-pentylpyrrole adducts that may mediate protein cross-linking. The Michael
      adducts appear not to be the direct source of the pyrrole, but the imine 32 and
      the enamine 35 are likely intermediates toward the five-membered ring.

PMID- 9548803
TI  - A single cyclic p-benzoquinone adduct can destabilize a DNA oligonucleotide
      duplex.
AB  - p-Benzoquinone (p-BQ), a stable metabolite of the human carcinogen benzene, forms
      two-ring benzetheno exocyclic base adducts with C, A, and G bases in DNA. As a
      part of a project for studying the biological effect of the p-BQ adducts, we
      report here on the first biophysical characterization of oligodeoxyribonucleotide
      duplexes containing a single site-specific p-BQ-C, using thermal denaturation and
      circular dichroism (CD). We find that the thermal and thermodynamic stabilities
      of the control duplex are reduced by p-BQ-C. The Tm value decreases by 12.6
      degrees C at the duplex concentration of 1.5 microM and the Delta G o by 10.2
      kcal/mol. The latter was determined from the concentration dependence of the Tm
      values. The destabilization has little dependence on the nature of the opposite
      base. This reduction is higher than that of the single base mismatches studied (
      4.9 to -7.9 kcal/mol) and is close to that observed with an adjacent double
      mismatch-containing duplex (-11.3 kcal/mol). The overall B-conformation of the
      duplex with a p-BQ-C is, however, only slightly altered, relative to the parent
      duplex, as shown by CD spectra. The p-BQ-C-containing duplex has been found
      recently to be a good substrate for the major human AP endonuclease as compared
      to an abasic site-containing duplex [Hang, B., et al. (1997) Biochemistry 36,
      15411-15418]. We now find that the thermodynamic properties and the localized
      conformational changes of a p-BQ-C-containing duplex are apparently related to
      those reported for a duplex containing an abasic site.

PMID- 9548804
TI  - Effect of ring size on conformations of aromatic amine-DNA adducts: the aniline
      C8 guanine adduct resides in the B-DNA major groove.
AB  - While the one-ring amine aniline (AN) has only slight genetic activity, the
      polycyclic aromatic amines 2-aminofluorene (AF) and 1-aminopyrene (AP) are
      significant mutagens and carcinogens. Moreover, the bulkier AP is more mutagenic
      per adduct than AF in the tetracycline-resistance gene of plasmid pBR322
      [Melchior et al. (1994) Carcinogenesis 15, 889]. To elucidate possible
      conformational origins of the differing mutagenic effects of these three adducts,
      which may stem from their differing ring sizes, we have examined their
      conformations in two mutation-susceptible sequences from the above gene:
      TTGAG*GCCG (sequence I) and GAATG*GTGC (sequence II), where G* = C8-modified
      guanine. No experimental high-resolution NMR data are yet available for the
      aniline adduct in a DNA duplex. Minimized potential energy calculations were
      carried out, using the molecular mechanics program DUPLEX to explore the
      conformation space of these adducts. In the case of AN, a relatively unperturbed
      B-DNA helix with the amine in the major groove was strongly favored in both
      sequences. In the case of AF- and AP-modified DNA, however, several differing
      conformations were competitive in energy. They included major groove structures,
      as well as conformations with syn-modified guanine and the polycyclic amine in
      the minor groove, or the amine rings intercalated into the helix with
      displacement of the modified guanine, in overall harmony with high-resolution NMR
      solution structures. Thus, aniline distorts DNA structure to a lesser extent than
      larger aromatic amine ring systems, since a number of different conformations are
      energetically feasible and have been observed for the larger systems. This result
      may be relevant to their enhanced mutagenicity and their repair propensity, in
      contrast to aniline's low mutagenic effect.

PMID- 9548805
TI  - Development of an enzyme-linked immunosorbent assay for atrazine mercapturic acid
      in human urine.
AB  - Improved assessments of human exposure to electrophilic chemicals require rapid
      and inexpensive analytical techniques that can detect specific urinary
      metabolites at low levels as needed for epidemiological screenings of large
      populations. The first aim of this study has been to apply rational hapten design
      strategies to develop a more sensitive and selective enzyme-linked immunosorbent
      assay for atrazine mercapturic acid. Polyclonal sheep antiserum was generated
      against an improved hapten, numerous coating antigen chemistries were evaluated,
      and assay conditions were optimized. An assay was developed with an IC50 of 0.08
      +/- 0.02 micrograms/L (K approximately with 10(-)10 M) for atrazine mercapturic
      acid. The assay exhibited greatest recognition of atrazine mercapturic acid
      relative to other known urinary metabolites of atrazine as well as other triazine
      herbicides. The assay was surprisingly selective to atrazine mercapturic acid
      over the structurally similar simazine mercapturic acid. Urine samples presented
      matrix effects due in part to the nonspecific effects of urinary salts, but 4
      fold dilution of urine achieved an overall method limit of quantitation of 0.3
      micrograms/L. Solid-phase extraction strategies were also developed in an attempt
      to increase the sensitivity of the overall method. However, a weak positive assay
      response was present in the solid-phase extracts of unspiked urines, resulting in
      accurate recovery of atrazine mercapturic acid at microgram/L.

PMID- 9548806
TI  - Dialkylquinonimines validated as in vivo metabolites of alachlor, acetochlor, and
      metolachlor herbicides in rats.
AB  - The oncogenicity of chloroacetanilide herbicides (1-5) is proposed to involve
      bioactivation to 2,6-dialkylbenzoquinonimines (quinonimines, 9) based on two
      earlier observations: (1) in vitro conversion of the alachlor (1) metabolite
      diethylaniline (7Et2) to 2, 6-diethylquinonimine (9Et2) which reacts readily with
      GSH and (2) induction of sister chromatid exchanges in human lymphocytes for the
      parent herbicides and their purported 9 metabolites. This hypothesis lacks in
      vivo evidence for 9 formation which might be provided by analysis of urine and
      tissue for thiol adducts of 9. Accordingly, two mercapturates (10Et2 and 10Me2)
      and a cysteine conjugate (11Me2) were prepared by addition of N-acetylcysteine or
      cysteine to 9Et2 and the 2,6-dimethyl homologue (9Me2). Mercapturate 10Et2 was
      characterized by HPLC using the urine of rats treated ip with hydroxyaniline
      8Et2, and both mercapturate 10Me2 and cysteine conjugate 11Me2 were found in the
      urine of mice administered hydroxyaniline 8Me2. The mercapturates were then
      converted to the N, N-dimethyl-2,6-dialkyl-4-methoxy-3-(methylthio)anilines
      (12Et2, 12EtMe, and 12Me2) by alkaline permethylation, thereby providing a method
      for analysis of 9-derived thiol adducts in urine and liver as the 12 derivatives
      by GC/MS with selected ion monitoring. The urine of rats 0-6 h after ip treatment
      with 1, butachlor (2), acetochlor (3), metolachlor (4), and dimethachlor (5) at
      0.74 mmol/kg yields permethylated derivatives which are definitively diagnostic
      for the 9 intermediates from each of the herbicides in amounts of 3-24-fold above
      the minimum detectable limit, as well as 1 and 2 orders of magnitude higher from
      the corresponding anilines (7) and hydroxyanilines (8), respectively. Similar
      liver analyses reveal tissue thiol adducts of 9 6 h after treatment with 7 and 8
      but not with the parent herbicides. The yields of urinary 9 derivatives from the
      parent herbicides are higher from the 2,6-diethyl series (1 and 2) and the 2
      ethyl-6-methyl derivatives (3 and 4) than from the 2, 6-dimethyl analogue (5).
      These findings provide direct evidence in vivo that quinonimines are metabolites
      of 1-5 in rats.

PMID- 9548807
TI  - Induction of p53 by the concerted actions of aziridine and quinone moieties of
      diaziquone.
AB  - The biologic functions attributed to the nucleophosphoprotein p53 have been
      increasing in recent years. Some studies suggested that wild type p53 is
      responsible for cell cycle arrest brought about as a response to exposure of
      mammalian cells to DNA-damaging agents. This cell cycle arrest occurs in order
      for cells to repair the damaged macromolecules. Extensively damaged cells are
      also thought to undergo apoptosis via the p53-dependent or -independent signal
      transduction pathways. In this study, we investigated the ability of
      diaziridinylbenzoquinones to increase p53 levels in the human breast cancer cell
      line MCF-7. Diaziquone (AZQ), an anticancer agent, and its derivatives,
      diaziridinequinone (DZQ) and methyldiaziridinequinone (MeDZQ), induced p53 in a
      dose- and time-dependent manner as measured by the electrophoretic mobility shift
      assay. Wild type p53 induction by AZQ was suppressed when DT-diaphorase activity
      was inhibited by pretreating the cells with dicumarol. Aside from their potent
      alkylating activity, these agents also undergo redox cycling as evidenced by
      oxygen consumption and the production of reactive oxygen species (ROS).
      Inhibition of ROS production by the antioxidant enzyme catalase reduced AZQ- and
      DZQ-mediated p53 induction by about 45%. Thiotepa, a non-quinone aziridine
      containing agent, and 1,4-benzoquinone (p-BQ), a redox cycling quinone, increased
      p53 levels. The nonalkylator oxygen-radical-generating agent menadione (MD)
      caused p53 induction only when MCF-7 cells were allowed to recover in drug-free
      media. On the basis of these data, we propose that the bioreductive activation of
      AZQ is a prerequisite for p53 induction. Moreover, the induction of p53 by AZQ
      requires both the quinone and the aziridine moieties of the AZQ molecule.
      Although AZQ and its analogues increased p53 levels in MCF-7 cells, p53 induction
      in these cells may not be responsible for the apoptosis seen upon treatment of
      MCF-7 cells with these agents. The uncoupling of p53 induction and apoptosis is
      evidenced by the generation of nucleosomal DNA laddering in aziridinequinone
      treated T47D cells, a breast cancer cell line bearing a p53 mutation.

PMID- 9548808
TI  - Synthesis and DNA reactivity of alpha-hydroxylated metabolites of nonsteroidal
      antiestrogens.
AB  - Tamoxifen [(E)-1-(4-(2-(N,N-dimethylamino)ethoxy)phenyl)-1, 2-diphenylbut-1-ene],
      a nonsteroidal antiestrogen, induces liver tumors in rats by a genotoxic
      mechanism. The mechanism of DNA adduct formation is believed to proceed via the
      formation of a reactive carbocation at the alpha-position from the alpha
      hydroxylated metabolite. Molecular mechanics calculations [Kuramochi, H. (1996)
      J. Med. Chem. 39, 2877-2886] have predicted that 4-substitution will affect the
      stability of the carbocation and thus will alter its reactivity toward DNA. We
      have synthesized the putative alpha-hydroxylated metabolites of 4
      hydroxytamoxifen [(E)-1-(4-(2-(N, N-dimethylamino)ethoxy)phenyl)-1-(4
      hydroxyphenyl)-3-hydroxy-2-phenyl but-1-ene] and idoxifene [(Z)-1-(4-iodophenyl)
      3-hydroxy-2-phenyl-1-(4-(2-(N-pyrrolidino) ethoxy)phenyl)but-1-ene] and compared
      their reactivities with DNA with that of alpha-hydroxytamoxifen [(E)-1-(4-(2-(N,
      N-dimethylamino)ethoxy)phenyl)-3-hydroxy-1,2-diphenylbut-1-ene]. As predicted,
      the bis-hydroxylated compound reacted with DNA in aqueous solution at pH 5 to
      give 12-fold greater levels of adducts than alpha-hydroxytamoxifen, whereas alpha
      hydroxyidoxifene gave one-half the number of adducts. The results demonstrate
      that idoxifene presents a significantly lower genotoxic hazard than tamoxifen for
      the treatment and prophylaxis of breast cancer.

PMID- 9548809
TI  - Chemical synthesis of a novel aromatic amine mutagen isolated from water of the
      Nishitakase River in Kyoto and a possible route of its formation.
AB  - Among five mutagenic compounds isolated from water samples, taken at sites below
      the sewage plants of the Nishitakase River in Kyoto, Japan, the structure of
      compound I has been determined to be 2-[2-(acetylamino)-4-[bis(2
      methoxyethyl)amino]-5-methoxyphenyl]-5-am ino-7-bromo-4-chloro-2H-benzotriazole
      (PBTA-1). Since this novel aromatic amine mutagen has characteristic substituents
      in its molecule, it is postulated that the azo dye, 2-[(2-bromo-4, 6
      dinitrophenyl)azo]-4-methoxy-5-[bis(2-methoxyethyl)amino]acetoanili de (AZO DYE
      1), used as an industrial material, is converted to the corresponding 2
      phenylbenzotriazole derivative with a reducing reagent and subsequently to PBTA-1
      by chlorination. In fact, AZO DYE-1 changed to the dechlorinated derivative of
      PBTA-1 (deClPBTA-1) on treatment with sodium hydrosulfite, and this reacted with
      sodium hypochlorite to produce PBTA-1. Moreover, the presence of deClPBTA-1 was
      confirmed in a river water sample, along with PBTA-1. PBTA-1 showed potent
      mutagenic activities in Salmonella typhimurium TA98 and YG1024, inducing 88 000
      and 3 000 000 revertants, respectively, per microg, with S9 mix. deClPBTA-1 was
      also mutagenic, but less potent. From these observations, it is suggested that
      PBTA-1 is produced from AZO DYE-1 through deClPBTA-1, during industrial processes
      at dyeing factories and the treatment of wastewater at sewage plants.

PMID- 9548810
TI  - Role of hydrophobic effects in the reaction of a polynuclear aromatic diol
      epoxide with oligodeoxynucleotides in aqueous solutions.
AB  - The need for large-scale direct synthesis of stereochemically defined and site
      specific benzo[alpha]pyrenediol epoxide-oligodeoxyribonucleotide adducts for
      detailed NMR and other biochemical and physicochemical studies has necessitated a
      better understanding of variables that lead to an enhancement of the reaction
      yields. It is shown that, in aqueous solution, the formation of noncovalent
      hydrophobic complexes between 7r, 8t-dihydroxy-9t,10t-epoxy-7,8,9,10
      tetrahydrobenzo[alpha] pyrene (BPDE) and the single-stranded oligonucleotide 5'
      d(CCATCGCTACC) precedes the covalent binding reaction of BPDE with the single
      deoxyguanosine residue. The yield of covalent reaction products (involving
      reaction of BPDE at the C10 position with the exocyclic amino group of the dG
      residue) increases with increasing DNA concentration and tends toward saturation
      at oligonucleotide single-strand concentrations above approximately 3 mM. The
      addition of NaCl (0.3 M) also tends to enhance the adduct reaction yields.
      However, organic solvents such as tetrahydrofuran in the reaction mixtures (10
      40%) decrease the stabilities of the noncovalent complexes, which in turn leads
      to reductions in the yields of covalent BPDE-dG oligonucleotide adducts. The
      efficiencies of formation of hydrophobic complexes were probed by fluorescence
      and UV absorption techniques using the BPDE tetrol hydrolysis product 7,8,9,10
      tetrahydroxytetrahydrobenzo[alpha]pyrene as a model system.

PMID- 9548811
TI  - 4-Amino-2-[4-[1-(benzyloxycarbonyl)-2(S)- [[(1,1-dimethylethyl)amino]carbonyl]
      piperazinyl]-6, 7-dimethoxyquinazoline (L-765,314): a potent and selective
      alpha1b adrenergic receptor antagonist.

PMID- 9548812
TI  - Inhibition of membrane-type 1 matrix metalloproteinase by hydroxamate inhibitors:
      an examination of the subsite pocket.
AB  - The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to
      mediate the activation of pro-gelatinase A (proMMP-2), which is associated with
      tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix
      (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play
      an important role in pathophysiological digestion of ECM. We studied the
      inhibitory effect of various hydroxamate MMP inhibitors, including known
      inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of
      MT1-MMP lacking the transmembrane domain (DeltaMT1) to further characterize the
      enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the
      inhibitory activities of various hydroxamates reveals general structural profiles
      affecting selectivities toward MMPs. In particular, a longer side chain at the
      P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For
      the P2' position, an alpha-branched alkyl group is critical for the binding
      toward DeltaMT1, while the introduction of a bulky group at the alpha-position of
      hydroxamic acid seems to diminish the activity against DeltaMT1. Summation of the
      data on the sensitivity of DeltaMT1 to various hydroxamate inhibitors indicates
      that (1) the volume of the S1' subsite of DeltaMT1 is similar to that of MMP-2, 
      3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites
      are narrower than those in other MMPs. On the basis of these results, the
      hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were
      synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed
      strong activity against DeltaMT1 over MMP-1, but no selectivity between DeltaMT1
      and MMP-9. These results are explained using molecular modeling studies conducted
      on MT1-MMP.

PMID- 9548813
TI  - The selective 5-HT1B receptor inverse agonist 1'-methyl-5-[[2'-methyl-4'-(5
      methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro-
      spiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289) potently blocks terminal 5
      HT autoreceptor function both in vitro and in vivo.
AB  - 5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are
      negatively linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D
      receptors (previously known as 5-HT1Dbeta and 5-HT1Dalpha, respectively),
      although encoded by two distinct genes, are structurally very similar.
      Pharmacologically, these two receptors have been differentiated using
      nonselective chemical tools such as ketanserin and ritanserin, but the absence of
      truly selective agents has meant that the precise function of the 5-HT1B and 5
      HT1D receptors has not been defined. In this paper we describe how, using
      computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D
      receptor antagonist 4 was structurally modified to produce the selective 5-HT1B
      receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol
      3-yl)biphenyl-4-yl]carbonyl]-2,3,6, 7-tetrahydrospiro[furo[2,3-f]indole-3,4'
      piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT
      autoreceptor function both in vitro and in vivo.

PMID- 9548814
TI  - Synthesis and antiviral evaluation of certain novel pyrazinoic acid C
      nucleosides.
AB  - Pyrazine (1,4-diazine) C-nucleosides constitute a rare class of nucleic acid
      analogues that has only recently been reported in the literature. As part of our
      ongoing investigation into the synthesis and reactivity of these compounds, we
      have developed an electrophilic esterification of a lithiated pyrazine C
      nucleoside (1) to give, following deprotection, the versatile intermediate ethyl
      3,5-dichloro-6-(beta-d-ribofuranosyl)pyrazine-2-carboxylate (4). This
      intermediate was subjected to a variety of reaction conditions to generate a
      series of pyrazinoic acid C-nucleosides. These compounds, along with 3, 5
      dichloro-2-(beta-d-ribofuranosyl)pyrazine (2) and 4, were evaluated for antiviral
      activity and cytotoxicity. No significant activity was observed for compounds 2
      and 5-9, but 4 was active against two herpes viruses and cytotoxic in the
      micromolar range.

PMID- 9548815
TI  - Design, synthesis, and antiviral evaluations of 1-(substituted benzyl)-2
      substituted-5,6-dichlorobenzimidazoles as nonnucleoside analogues of 2,5,6
      trichloro-1-(beta-D-ribofuranosyl)benzimidazole.
AB  - We have recently reported that certain ribosylated polyhalogenated benzimidazoles
      are potent and selective inhibitors of HCMV replication at noncytotoxic
      concentrations. To extend the structure-activity relationship beyond these first
      generation compounds, we alkylated 5,6-dichloro-2-substituted-benzimidazoles with
      either a series of substituted benzyl halides or (2-bromoethyl)benzene to obtain
      five series of nonnucleoside analogues. Evaluation of these compounds for
      activity against herpes viruses revealed that the new compounds were less active
      than the benzimidazole ribonucleosides against human cytomegalovirus (HCMV) and
      inactive against herpes simplex virus type 1 (HSV-1). However, as part of our
      broader antiviral testing, we found that some of these compounds were active
      against HIV. Comparisons of the biological data revealed that a chloro or bromo
      group was required at the 2-position for the best separation of activity against
      HIV and cytotoxicity. Evaluation of the most active compounds against drug
      resistant HIV suggested that they act by a mechanism other than inhibition of
      reverse transcriptase.

PMID- 9548816
TI  - Selective Pneumocystis carinii dihydrofolate reductase inhibitors: design,
      synthesis, and biological evaluation of new 2,4-diamino-5-substituted-furo[2,3
      d]pyrimidines.
AB  - Nonclassical antifolates, 2,4-diamino-5-substituted-furo[2, 3-d]pyrimidines 3-12
      with bridge region variations of C8-S9, C8-N9, and C8-O9 and 1-naphthyl, 2
      naphthyl, 2-phenoxyphenyl, 4-phenoxyphenyl, and 2-biphenyl side chains were
      synthesized as phenyl ring appended analogues of previously reported 2, 4-diamino
      5-(anilinomethyl)furo[2,3-d]pyrimidines. The phenyl ring appended analogues were
      designed to specifically interact with Phe69 of dihydrofolate reductase (DHFR)
      from Pneumocystis carinii (pc) to afford selective inhibitors of pcDHFR.
      Additional substituted phenyl side chains which include 2,5-dichloro, 3,4
      dichloro, 3,4,5-trichloro, 3-methoxy, and 2,5-dimethoxy analogues 13-17 were also
      synthesized. The compounds were prepared by nucleophilic displacement of 2,4
      diamino-5-(chloromethyl)furo[2,3-d]pyrimidine(2) with the appropriate thiol,
      amine, or naphthol. Compound 2 was obtained from 2,4-diamino-6-hydroxypyrimidine
      and 1, 3-dichloroacetone. The compounds were evaluated as inhibitors against DHFR
      from P. carinii, Toxoplasma gondii, and rat liver. Two analogues, 2,4-diamino-5
      [(2'-naphthylthio)methyl]furo[2, 3-d]pyrimidine (5) and 2,4-diamino-5-[(2'
      phenylanilino)methyl]furo[2,3-d]pyrimidine (11) showed significant selectivity
      and potency for pcDHFR compared to trimethoprim. The X-ray crystal structure of 5
      with pcDHFR was also carried out, which corroborated the design rationale and
      indicated a hydrophobic interaction of the naphthalene ring of 5 and Phe69 of
      pcDHFR which is responsible, in part, for the more than 18-fold selectivity of 5
      for pcDHFR as compared with rat liver DHFR.

PMID- 9548817
TI  - Synthesis and pharmacology of conformationally restricted raloxifene analogues:
      highly potent selective estrogen receptor modulators.
AB  - The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor
      modulator (SERM) which is currently under clinical evaluation for the prevention
      and treatment of postmenopausal osteoporosis. In vivo structure-activity
      relationships and molecular modeling studies have indicated that the orientation
      of the basic amine-containing side chain of 1, relative to the stilbene plane, is
      an important discriminating factor for the maintenance of tissue selectivity. We
      have constructed a series of analogues of 1 in which this side chain is held in
      an orientation which is orthogonal to the stilbene plane, similar to the low
      energy conformation predicted for raloxifene. Herein, we report on the synthesis
      of these compounds and on their activity in a series of in vitro and in vivo
      biological assays reflective of the SERM profile. In particular, we describe
      their ability to (1) bind the estrogen receptor, (2) antagonize estrogen
      stimulated proliferation of MCF-7 cells in vitro, (3) stimulate TGF-beta3 gene
      expression in cell culture, (4) inhibit the uterine effects of ethynyl estradiol
      in immature rats, and (5) potently reduce serum cholesterol and protect against
      osteopenia in ovariectomized (OVX) rats without estrogen-like stimulation of
      uterine tissue. These data demonstrate that one of these compounds, LY357489,4,
      is among the most potent SERMs described to date with in vivo efficacy on bone
      and cholesterol metabolism in OVX rats at doses as low as 0.01 mg/kg/d.

PMID- 9548819
TI  - d-Fused [1]benzazepines with selective in vitro antitumor activity: synthesis and
      structure-activity relationships.
AB  - The synthesis of novel quinolino[3,2-d][1]benzazepines and pyrido[3,2
      d][1]benzazepines is described. The in vitro antitumor activity of the compounds
      has been tested in the antitumor screening of the National Cancer Institute
      (NCI). Several 2,4-diarylpyrido[3, 2-d][1]benzazepin-6-ones and -thiones turned
      out to exhibit considerable cytotoxicity for tumor cells. For studies of SAR
      within these series, substituents were introduced into the aromatic rings of the
      parent systems. Compounds from the thiolactam series tended to show higher
      potency than the corresponding lactams. Prominent compounds with noteworthy
      activity and remarkable selectivity for renal cancer cell lines are the lactams
      10c, 10g, and 10h and the corresponding thiolactams 11c, 11g, and 11h.
      Methylation of the azepine nitrogen leads to complete loss of activity, whereas
      annelation of a triazolo ring at the lactam site or transformation of the
      thiolactam function to a thiolactim ether results in decreased antitumor activity
      and selectivity. Consequently, the secondary lactam or thiolactam structure of
      the seven-membered ring has to be regarded as essential for selective antitumor
      activity.

PMID- 9548818
TI  - Synthesis and antiviral activity of novel acyclic nucleosides: discovery of a
      cyclopropyl nucleoside with potent inhibitory activity against herpesviruses.
AB  - A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'-
      and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated
      for their antiherpetic activity. Among those, 9-[[cis-1', 2'
      bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine (3) showed extremely potent
      antiviral activity against herpes simplex virus type-1 (HSV-1) with good
      selectivity. Both enantiomers of 3 were synthesized starting from chiral
      epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a)
      exhibited strong antiherpetic activity (IC50 of 0.020 microg/mL against HSV-1
      Tomioka vs 0.81 microg/mL for acyclovir). Enantiomer 3a was also more inhibitory
      than acyclovir against varicella-zoster virus (VZV) but ineffective against human
      immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine
      kinase (TK) very efficiently. The relationship between conformation and
      antiherpetic activity in this series of compounds is discussed.

PMID- 9548820
TI  - Epidoxoform: a hydrolytically more stable anthracycline-formaldehyde conjugate
      toxic to resistant tumor cells.
AB  - The recent discovery that the formaldehyde conjugates of doxorubicin and
      daunorubicin, Doxoform and Daunoform, are cytotoxic to resistant human breast
      cancer cells prompted the search for hydrolytically more stable anthracycline
      formaldehyde conjugates. Doxoform and Daunoform consist of two molecules of the
      parent drug bound together with three methylene groups, two forming oxazolidine
      rings and one binding the oxazolidines together at their 3'-amino nitrogens. The
      4'-epimer of doxorubicin, epidoxorubicin, reacts with formaldehyde at its amino
      alcohol functionality to produce a conjugate, Epidoxoform, in 59% yield whose
      structure consists of two molecules of epidoxorubicin bound together with three
      methylene groups in a 1, 6-diaza-4,9-dioxabicyclo[4.4.1]undecane ring system. The
      structure was established from spectroscopic data and is consistent with products
      from reaction of simpler vicinal trans-amino alcohols with formaldehyde.
      Epidoxoform hydrolyzes at pH 7.3 to an equilibrium mixture with dimeric and
      monomeric epidoxorubicin-formaldehyde conjugates without release of formaldehyde
      or epidoxorubicin. The hydrolysis follows the rate law (A if B) if C + D where A
      (Epidoxoform) is in rapid equilibrium with B, and B is in slow equilibrium with C
      and D. The forward rate constant for A/B going to C+D gives a half-life of
      approximately 2 h at 37 degrees C. At equilibrium the mixture is stable for at
      least 2 days. At pH 6.0, hydrolysis proceeds with first-order kinetics to
      epidoxorubicin and formaldehyde with a half-life of 15 min at 37 degrees C.
      Epidoxoform and epidoxorubicin plus formaldehyde react with the self
      complementary DNA octamer (GC)4 to yield five drug-DNA adducts which have
      structures analogous to the doxorubicin-DNA adducts from reaction of Doxoform
      with (GC)4. Epidoxoform is 3-fold more toxic to MCF-7 human breast cancer cells
      and greater than 120-fold more toxic to MCF-7/ADR resistant cells than
      epidoxorubicin. Epidoxoform in equilibrium with its hydrolysis products is
      greater than 25-fold more toxic to resistant cells with respect to
      epidoxorubicin.

PMID- 9548827
TI  - Changes for Volume 61

PMID- 9548822
TI  - Azapeptides as inhibitors and active site titrants for cysteine proteinases.
AB  - Ester and amide derivatives of alpha-azaglycine (carbazic acid, H2NNHCOOH), alpha
      azaalanine, and alpha-azaphenylalanine (i.e., Ac-l-Phe-NHN(R)CO-X, where X = H,
      CH3, or CH2Ph, respectively) were synthesized and evaluated as inhibitors of the
      cysteine proteinases papain and cathepsin B. The ester derivatives inactivated
      papain and cathepsin B at rates which increased dramatically with leaving group
      hydrophobicity and electronegativity. For example, with 8 (R = H, X = OPh) the
      apparent second-order rate constant for papain inactivation was 67 600 M-1 s-1.
      Amide and P1-thioamide derivatives do not inactivate papain, nor are they
      substrates; instead they are weak competitive inhibitors (0.2 mM < Ki < 4 mM).
      Inactivation of papain involves carbamoylation of the enzyme, as demonstrated by
      electrospray mass spectrometry. Active site titration indicated a 1:1
      stoichiometry for the inactivation of papain with 8, and both inactivated papain
      and cathepsin B are highly resistant to reactivation by dialysis (t1/2 > 24 h at
      4 degrees C). Azaalanine derivatives Ac-L-Phe-NHN(CH3)CO-X inactivate papain ca.
      400- 900-fold more slowly than their azaglycine analogues, consistent with the
      planar configuration at Nalpha of the P1 residue and the very substantial
      stereoselectivity of papain for L- vs D- residues at the P1 position of its
      substrates. Azaglycine derivative 9 (R = H, X = OC6H4NO2-p) inactivates papain
      extremely rapidly (>70 000 M-1 s-1), but it also decomposes rapidly in buffer
      with release of nitrophenol (kobs = 0.13 min-1); under the same conditions 8
      shows <7% hydrolysis over 24 h. This nitrophenol release probably involves
      cyclization to an oxadiazolone since 17 (R = CH3, X = OC6H4NO2-p), which cannot
      form an isocyanate, releases nitrophenol almost as rapidly (kobs = 0.028 min-1).
      Cathepsin C, another cysteine proteinase with a rather different substrate
      specificity (i.e., aminopeptidase), was not inactivated by 8, indicating that the
      inactivation of papain and cathepsin B by azapeptide esters is a specific
      process. Their ease of synthesis coupled with good solution stability suggests
      that azapeptide esters may be useful as active site titrants of cysteine
      proteinases and probes of their biological function in vivo.

PMID- 9548821
TI  - Structure-activity studies on anticonvulsant sugar sulfamates related to
      topiramate. Enhanced potency with cyclic sulfate derivatives.
AB  - We have explored the structure-activity relationship (SAR) surrounding the
      clinically efficacious antiepileptic drug topiramate (1), a unique sugar
      sulfamate anticonvulsant that was discovered in our laboratories. Systematic
      structural modification of the parent compound was directed to identifying potent
      anticonvulsants with a long duration of action and a favorable neurotoxicity
      index. In this context, we have probed the pharmacological importance of several
      molecular features: (1) the sulfamate group (6-8, 22-25, 27, 84), (2) the linker
      between the sulfamate group and the pyran ring (9, 10, 21a,b), (3) the
      substituents on the 2,3- (58-60, 85, 86) and 4, 5-fused (30-38, 43, 45-47, 52,
      53) 1,3-dioxolane rings, (4) the constitution of the 4,5-fused 1,3-dioxolane ring
      (2, 54, 55, 63-68, 76, 77, 80, 83a-r, 84-87, 90a, 91a, 93a), (5) the ring oxygen
      atoms (95, 96, 100-102, 104, 105), and (6) the absolute stereochemistry (106 and
      107). We established the C1 configuration as R for the predominant alcohol
      diastereomer from the highly selective addition of methylmagnesium bromide to
      aldehyde 15 (16:1 ratio) by single-crystal X-ray analysis of the major
      diastereomer of sulfamate 21a. Details for the stereoselective syntheses of the
      hydrindane carbocyclic analogues 95, 96, 100, and 104 are presented. We also
      report the synthesis of cyclic imidosulfites 90a and 93a, and imidosulfate 91a,
      which are rare examples in the class of such five-membered-ring sulfur species.
      Imidosulfite 93a required the preparation and use of the novel sulfur dichloride
      reagent, BocN=SCl2. Our SAR investigation led to the impressive 4,5-cyclic
      sulfate analogue 2 (RWJ-37947), which exhibits potent anticonvulsant activity in
      the maximal electroshock seizure (MES) test (ca. 8 times greater than 1 in mice
      at 4 h, ED50 = 6.3 mg/kg; ca. 15 times greater than 1 in rats at 8 h, ED50 = 1.0
      mg/kg) with a long duration of action (>24 h in mice and rats, po) and very low
      neurotoxicity (TD50 value of >1000 mg/kg at 2 h, po in mice). Cyclic sulfate 2,
      like topiramate and phenytoin, did not interfere with seizures induced by
      pentylenetetrazole, bicucculine, picrotoxin, and strychnine; also, 2 was not
      active in diverse in vitro receptor binding and uptake assays. However, 2 turned
      out to be a potent inhibitor of carbonic anhydrase from different rat tissue
      sources (e. g., IC50 of 84 nM for the blood enzyme and 21 nM for the brain
      enzyme). An examination of several analogues of 2 (83a-r, 85-87, 90a, 91a, 93a)
      indicated that potent anticonvulsant activity is associated with relatively small
      alkyl substituents on nitrogen (Me/H, 83a; Me/Me, 83m; Et/H, 83b; allyl/H, 83e; c
      Pr/H, 83j; c-Bu/H, 83k) and with limited changes in the cyclic sulfate group,
      such as 4,5-cyclic sulfite 87a/b. The potent anticonvulsants 83a and 83j had
      greatly diminished carbonic anhydrase inhibitory activity; thus, inhibition of
      this enzyme may not be a significant factor in the anticonvulsant activity. The
      alpha-L-sorbopyranoses 67, 68, and 80, which mainly possess a skew conformation
      (ref 29), were nearly twice as potent as topiramate (1). The L-fructose
      enantiomers of 1 (106) and 2 (107), synthesized from L-sorbose, were found to
      have moderate anticonvulsant activity, with eudysmic ratios (MES ED50 in mice at
      4 h, po) of 1:106 = 1.5 and 2:107 = 3.5. The log P values for 1 and 2 were
      determined experimentally to be 0.53 and 0.42, respectively, which are less than
      the optimal 2.0 for CNS active agents. However, analogues with more favorable
      calculated log P (clogP) values, in conjunction with just minor steric
      perturbation according to the developed SAR profile, such as 47 (clogP = 2.09),
      83m (1.93), and 86 (1.50), did not display improved potency: 47 is less potent
      than 1, 83m is equipotent with 2, and 86 is less potent than 2. Although the
      measured log P value for diethyl analogue 31 is 1.52, this did not translate into
      enhanced potency relative to 1. (ABSTRACT TRUNCATED)

PMID- 9548828
TI  - Unusual Polyoxygenated Monoterpenes from the Antarctic Alga Pantoneura
      plocamioides
AB  - Six new polyoxygenated marine monoterpenes have been isolated from the Antarctic
      alga Pantoneura plocamioides. The structure and relative stereochemistry of these
      compounds, denominated pantopyranoids A-C (1-3), and pantoisofuranoids A-C (4-6)
      were determined on basis of spectroscopic evidence.

PMID- 9548829
TI  - Enantioselective Total Syntheses of (-)-7betaH-Eudesmane-4alpha,11-diol and (+)
      ent-7betaH-Eudesmane-4alpha,11-diol
AB  - The syntheses of (-)-7betaH-eudesmane-4alpha,11-diol (2) and (+)-ent-7betaH
      eudesmane-4alpha,11-diol (ent-2) were carried out starting from (-)- and (+)
      dihydrocarvones. As a result, the structure, including absolute configuration, of
      the naturally occurring eudesmane-4,11-diol isolated from Pluchea arguta was
      determined to be (+)-ent-7betaH-eudesmane-4alpha,11-diol (ent-2).

PMID- 9548830
TI  - Tribenzylbutyrolactones and Dibenzyldiphenyl-4,5,6,7-tetrahydrobenzofuranones
      from Kyrtuthrix maculans
AB  - Ten novel compounds, maculalactones B-K (2-11), have been isolated from the
      marine cyanobacterium Kyrtuthrix maculans. Their structures, which involve either
      three benzyl groups substituted on a butyrolactone ring or two benzyl and two
      phenyl groups substituted on a 4,5,6,7-tetrahydrobenzofuranone nucleus, were
      determined by 2D NMR spectroscopy. Some speculation is made concerning the
      biogenesis of these two novel classes of natural products.

PMID- 9548831
TI  - Fractionation Protocol for the Isolation of Polypeptides from Plant Biomass
AB  - A fractionation protocol for the isolation of a highly purified polypeptide
      fraction from plant biomass is described. The procedure dereplicates ubiquitous
      substance classes known to interfere with bioassays often used in natural product
      based drug discovery programs. The protocol involves pre-extraction with
      dichloromethane, extraction with ethanol (50%), removal of tannins with
      polyamide, removal of low-molecular-weight components with size-exclusion
      chromatography over Sephadex G-10, and final removal of salts and polysaccharides
      with solid-phase extraction using reversed-phase cartridges. The method has been
      applied to the aerial parts of Viola arvensis, resulting in the isolation of a
      peptide fraction that on further separation yielded a novel 29-residue
      macrocyclic polypeptide named varv peptide A, cyclo(
      TCVGGTCNTPGCSCSWPVCTRNGLPVCGE-).

PMID- 9548832
TI  - Donnaienin, a New Acetogenin Bearing a Hydroxylated Tetrahydrofuran Ring
AB  - A novel Annonaceous acetogenin, donnaienin (1), was isolated from the roots of
      Goniothalamus donnaiensis. Its structure and stereochemistry were elucidated on
      the basis of spectral data and chemical evidence. This compound represents an
      unusual type of Annonaceous acetogenin, bearing a hydroxylated tetrahydrofuran
      ring.

PMID- 9548833
TI  - Revised Relative and Absolute Stereochemistry of (+)-Purpurin
AB  - The relative and absolute stereochemistries of (+)-purpurin (3), a flavanone
      natural product from Tephrosia, were determined to be 2S,7aR,10S,10aS by
      synthesis from semiglabrin in conjunction with X-ray crystallographic analysis.

PMID- 9548834
TI  - Studies on the Synthesis of Elegan-Type Linear Diterpenes: The Efficient Total
      Syntheses of Eleganolone, Eleganolone Acetate, Elegandiol, Eleganonal, and
      Epoxyeleganolone
AB  - The first total syntheses of five elegan-type linear diterpenes-eleganolone (1),
      eleganolone acetate (2), elegandiol (3), eleganonal (4), and epoxyeleganolone (5)
      were accomplished starting from (E,E)-farnesol (6) via four to six steps,
      successively, with high overall yield. The key step was the alkylation reaction
      of silyl cyanide with allylic iodide.

PMID- 9548835
TI  - Dammarane Triterpenes from the Leaves of Securinega melanthesoides
AB  - Two new dammarane triterpenoids, trans-securinegin [(20S)-24-methylidenedammarane
      3alpha-yl(2E)-3-(4-hydroxyphenyl)-2-propenate (1)] and cis-securinegin [(20S)-24
      methylidenedammarane-3alpha-yl(2Z)-3-(4-hydroxyphenyl)-2-propenate (2)], were
      isolated from the leaves of Securinega melanthesoides, along with the known
      compound bergenin. The structures of 1 and 2 were elucidated using spectroscopic
      methods, mainly 2D NMR techniques.

PMID- 9548836
TI  - Coluteol and Colutequinone B, More Antifungal Isoflavonoids from Colutea
      arborescens
AB  - The new antifungal compounds, coluteol (3',5'-dihydroxy-7,2',4'
      trimethoxyisoflavan) and colutequinone B (7,4',6'-trimethoxyisoflavan-2',5'
      quinone) have been isolated from the root bark of Colutea arborescens (common
      bladder senna) and identified by a combination of 1H- and 13C-NMR techniques.

PMID- 9548837
TI  - A Novel Insect Antifeedant Nonprotein Amino Acid from Calotropis gigantea
AB  - Giganticine (1), a novel nonprotein amino acid, has been isolated from a methanol
      extract of the root bark of Calotropis gigantea and its structure established by
      spectroscopic methods. It exhibited a significant antifeedant activity against
      nymphs of the desert locust Schistocerca gregaria.

PMID- 9548838
TI  - New Sesquiterpene Lactones and Other Constituents from Helianthuspetiolaris
AB  - Three new sesquiterpene lactones, 11alpha,13-dihydroxydehidrocostuslactone (1),
      the unusual 5, 10-epoxygermacranolide 4,15-anhydrohelivypolide (2), and 3-methoxy
      1,2-anhydridoniveusin A (4), together with the 5,10-epoxygermacranolide
      helivypolide, four known 3,10-furanoheliangolides, and five known kaurane- and
      trachylobane-type diterpenes, have been isolated from Helianthus petiolaris.

PMID- 9548839
TI  - Geranyl Phenyl Ethers from the New Zealand Liverwort Trichocolea hatcheri
AB  - Methyl 4-(geranyloxy)-3-hydroxybenzoate (6), previously unreported, has been
      identified from the New Zealand liverwort Trichocolea hatcheri. Four new related
      3-hydroxybenzoates 7-10 were also found, with a carbonyl at C-5 of the geranyl
      group and various double bond arrangements. Two known geranyl phenyl ethers 1 and
      3, found in other Trichocolea species, were also identified.

PMID- 9548840
TI  - Strychnochrysine, a New Bisindole Alkaloid from the Roots of Strychnos nux
      vomica1
AB  - The reinvestigation of Strychnos nux-vomica resulted in the isolation of a
      colored monoquaternary bisindole alkaloid from the roots. The structure of this
      new orange substance, strychnochrysine (1), was defined by detailed spectroscopic
      methods.

PMID- 9548841
TI  - Malyngamides M and N from the Hawaiian Red Alga Gracilaria coronopifolia
AB  - Two new malyngamides, M and N (1, 2), were isolated along with malyngamide I
      acetate (3) from the Hawaiian red alga Gracilaria coronopifolia. Our results
      suggest that malyngamide N (2) is a revised structure of deacetoxystylocheilamide
      (5). The absolute configuration of malyngamide I acetate was deduced to be 3
      using the reversed octant rule.

PMID- 9548844
TI  - Combination of LC-MS and LC-NMR as a Tool for the Structure Determination of
      Natural Products
AB  - Application of both LC-MS and LC-NMR to a partially purified extract of Vernonia
      fastigiataled to the direct identification of antibacterial sesquiterpene
      lactones 1-9 without isolation of individual compounds. The rapid structural
      analysis of both major and minor components of this class of compounds
      demonstrated the power of structure-guided screening as a complementary method to
      assay-guided screening.

PMID- 9548845
TI  - Minor Flavanones from Erythrina abyssinica
AB  - Four new prenylated flavanones, abyssinone-V 4'-methyl ether (1) and
      abyssinoflavanones IV (2), V (3), and VI (4), have been isolated as minor
      flavanones from the African medicinal plant, Erythrina abyssinica, together with
      a known flavanone, sigmoidin D. The structure elucidation of compounds 1-4 by
      spectroscopic studies is described.

PMID- 9548846
TI  - Predomination of Dimers over Naturally Occurring Anthraquinones in Soil
AB  - Four bianthraquinones and two monoanthraquinones were isolated as the major soil
      anthraquinones from a volcanic ash soil in Japan. They were identified as a new
      natural product 5,5'-biphyscion (named hinakurin) (3) and five known compounds,
      chrysotalunin (1), (-)-7,7'-biphyscion (2), microcarpin (4), chrysophanol (5),
      and physcion (6) using MS, 1D NMR, and 2D NMR techniques. Although the dimers (1
      4) are rarely found as natural products, they, along with 5 and 6, were
      ubiquitous and predominant over other anthraquinones in various soils from Japan
      and Nepal.

PMID- 9548847
TI  - Antibacterial steroidal alkaloids from Sarcococca saligna.
AB  - Two new pregnane-type steroidal alkaloids, saligcinnamide [(20S,2'E)-20-(N,N
      dimethylamino)-3beta-(3'-phenyl-2'-propenyl-N-meth ylamido)pregnane](1) and N(a)
      methyl epipachysamine-D [(20S)-20-(N,N-dimethylamino)-3beta-(N
      methylbenzamido)pregnane](2 ), along with a known base, epipachysamine D [(20S)
      20-(N,N-dimethylamino)-3beta-(benzamido)pregnane] (3), were isolated from the
      EtOH extracts of the roots and stems of Sarcococca saligna. The new bases
      exhibited antibacterial activity against several human pathogenic bacteria. Two
      derivatives of 1, dihydrosaligcinnarnide [(20S)-20-(N,N-dimethylamino)-3beta-(3'
      phenylpropionoyl-N-meth ylamido)pregnane](4) and dihydrosaligcinnamine [(20S)-20
      (N,N-dimethylamino)-3beta-N-(3'-phenylpropyl-N-methylamino)pre gnane](5), and a
      derivative of 2, N(a)-methyl epipachysamine [(20S)-20-(N,N-dimethylamino)-3beta
      (N-benzyl,N-methylamino)pregnane](6) were prepared and their antibacterial
      activity determined.

PMID- 9548848
TI  - Isolation and Identification of Two l-Azetidine-2-carboxylic Acid-Degrading Soil
      Microorganisms, Enterobacter agglomerans and Enterobacter amnigenus
AB  - Soil samples collected at several times during the growing season and at
      different locations within Convallaria majalis beds in Ann Arbor, MI, were
      screened for their ability to grow with the cyclic amino acid, l-azetidine-2
      carboxylic acid (l-A-2-C), as their sole nitrogen source (i.e., metabolize l-A-2
      C). Two different soil microorganisms were isolated, characterized, and
      identified using fundamental selection methods, the standard battery of
      biochemical characterization tests, and scanning electron microscopy. The
      assignment of the identity of these organisms as Enterobacter agglomerans and
      Enterobacter amnigenus was further verified by comparison with authentic
      microbial samples obtained from ATCC that were able to utilize l-A-2-C as their
      sole nitrogen source.

PMID- 9548849
TI  - Calyxin H, Epicalyxin H, and Blepharocalyxins A and B, Novel Diarylheptanoids
      from the Seeds of Alpinia blepharocalyx
AB  - Four unprecedented diarylheptanoids-calyxin H (1) and epicalyxin H (2),
      possessing a diarylheptanoid unit and a chalcone moiety, and blepharocalyxins A
      (3) and B (4), possessing two diarylheptanoid units and a chalcone moiety-were
      isolated from the seeds of Alpiniablepharocalyx. The structures of 1-4, including
      absolute stereochemistry, were elucidated by spectroscopic means and after a
      consideration of their biogenesis.

PMID- 9548850
TI  - Six New Diarylbutane Lignans from Justicia procumbens
AB  - Six new diarylbutane lignans, namely, justin A (1), (-)-dihydroclusin diacetate
      (2), secoisolariciresinol dimethyl ether diacetate (3), 5-methoxy-4,4'-di-O
      methylsecolariciresinol diacetate (4), justin B (5), and justin C (6), together
      with three known diarylbutane lignans [2,3-demethoxysecisolintetralin acetate
      (7), secoisolariciresinol dimethyl ether (8), and 5-methoxy-4,4'-di-O
      methylsecolariciresinol (9)], were isolated from the whole plant of Justicia
      procumbens. Their structures were established by spectral analysis.

PMID- 9548851
TI  - New Sesquiterpene Lactones from Illicium floridanum
AB  - In continuation of our phytochemical investigation of Illicium floridanum Ellis
      (American star anise, star bush), three new sesquiterpene lactones possessing the
      anisatin-type carbon skeleton (8,9-seco-prezizaane skeleton), 14-acetoxy-3
      oxofloridanolide (1), 13-acetoxy-14-(n-butyryloxy)floridanolide (2), and 3beta
      acetoxy-14-n-butyryloxy-10-deoxyfloridanolide (3), were isolated from fruits of
      this plant. Their structures were elucidated by 1D and 2D NMR measurements. The
      molecular structure of 1 was obtained by single crystal X-ray diffraction. The
      11,3-delta-lactone structure of the compound previously described as
      debenzoyldunnianin in our previous communication, on grounds of NMR spectral
      evidence and X-ray crystallographic analysis is revised to a delta-lactone closed
      between C-11 and C-7 (compound 4). The neurotoxic sesquiterpene lactone anisatin
      (5) and its isomer 2alpha-hydroxyneoanisatin (3-deoxy-2alpha-hydroxyanisatin, 6)
      were also isolated and identified by spectroscopic means. The presence of the
      neurotoxin 5 in relatively high amounts in the fruits and leaves confirms and
      explains early reports on the toxicity of this plant.

PMID- 9548852
TI  - Three new diterpenes from the marine soft coral Lobophytum crassum.
AB  - Three new terpenoid metabolites (1-3) were isolated from the CH2Cl2 extract of
      the soft coral Lobophytum crassum together with the eudesmane derivative 4 and
      the known cembrane (2S,7S,8S)-sarcophytoxide (5). Compound 1 is a new cembrane
      based diterpene with an C7-C8-epoxide and a methyl ester functionality at C-16.
      (3E,5Z)- (2) and (3Z,5E)-2-methyl-6-(4a'-methyl-8'-methylene-trans-perhydr 
      onaphthalen-2'-yl)hepta-3,5-dien-2-ol (3) represent two new carbon-carbon double
      bond isomers of 4, which has the 3E,5E-configuration. The structures of 1-5 were
      established by interpretation of their spectroscopic data, mainly 1D and 2D NMR
      and MS. Biological activity evaluation of compounds 1 and 5 and the crude
      extracts was carried out using agar diffusion assays toward microbial targets and
      ELISA assays for investigating the inhibition of HIV-1 reverse transcriptase and
      p56lck tyrosine kinase.

PMID- 9548853
TI  - Isolation of 1-Methylherbipoline Salts of Halisulfate-1 and of Suvanine as Serine
      Protease Inhibitors from a Marine Sponge, Coscinoderma mathewsi
AB  - Bioassay-guided isolation of serine protease inhibitors from a marine sponge,
      Coscinoderma mathewsi, has yielded 1-methylherbipoline salts of halisulfate-1 and
      of suvanine. Structures of these compounds were identified by spectroscopic
      analyses and literature data. Antithrombin and antitrypsin activity was
      determined.

PMID- 9548854
TI  - Gloeolactone, a New Epoxy Lactone from a Blue-Green Alga
AB  - A novel lactone, gloeolactone (1), has been isolated from the blue-green alga,
      Gloeotrichia sp. The structure of this compound has been elucidated from a
      detailed analysis of the NMR spectra. This compound was shown to be toxic to
      brine shrimp.

PMID- 9548855
TI  - Synthesis of Cycleanine Mono-N-oxides
AB  - Oxidation of cycleanine (3) with m-chloroperbenzoic acid gave two diastereomeric
      N-oxides (1 and 2), and their stereochemistry was unambiguously determined on the
      basis of spectroscopic evidence. The NMR spectra of synthetic cycleanine mono-N
      oxides 1 and 2 were significantly different from those of the natural product
      previously reported to be cycleanine N-oxide.

PMID- 9548856
TI  - 10-Hydroxyaloin B 6'-O-Acetate, an Oxanthrone from Aloe claviflora
AB  - Analysis of the leaf exudate of Aloe claviflora resulted in the isolation of a
      new oxanthrone, 10-hydroxyaloin B 6'-O-acetate (1), whose structure was
      determined on the basis of spectral evidence as well as by conversion to the
      known compound 10-hydroxyaloin B (2).

PMID- 9548857
TI  - New metabolites from the sponge Spongia agaricina.
AB  - The sponge Spongia agaricina from Tarifa, Cadiz, Spain, contains two new 9,11
      secosterols, [3-0-deacetylluffasterol B (1) and 3-0-deacetyl-22,23-dihydro-24,28
      dehydroluffasterol B (2)] and two new sesterterpenoids [12,16-di-epi-12-0
      deacetyl-16-0-acetylfuroscalarol (3) and 16-epi-scalarolbutenolide (4)], in
      addition to the known compounds 5-15. The structures of all compounds were
      elucidated by interpretation of' spectroscopic data. The metabolites 1-3 showed
      significant cytotoxicity against four tumor cell lines (C50 1 microgram/mL).

PMID- 9548858
TI  - A Trachylobane Diterpenoid from Xylopia aethiopica
AB  - A new trachylobane derivative identified as 7alpha-hydroxytrachyloban-19beta-oic
      acid (1) has been isolated from the bark of Xylopia aethiopica and its structure
      elucidated by various NMR techniques and molecular modeling.

PMID- 9548859
TI  - Madangamines B-E, Pentacyclic Alkaloids from the Marine Sponge Xestospongia
      ingens
AB  - Four new pentacyclic alkaloids, madangamines B-E (3-6), have been isolated from
      the marine sponge Xestospongia ingens collected in Papua New Guinea.

PMID- 9548860
TI  - Violarvensin, a new flavone di-C-glycoside from Viola arvensis.
AB  - A new flavonoid di-C-glycoside, violarvensin (1), was isolated from the aerial
      parts of Viola arvensis, together with the known derivative violanthin (2). The
      structure of 1 was established as apigenin-6-C-beta-D-glucopyranosyl-8-C-beta-D-6
      deoxygulopyrano side by spectral analysis.

PMID- 9548862
TI  - Limaciamine, a New Diacylguanidine Isolated from the North Sea Nudibranch Limacia
      clavigera
AB  - Limaciamine (1), a new symmetrical diacylguanidine, has been isolated from skin
      extracts of the North Sea dorid nudibranch Limacia clavigera.

PMID- 9548861
TI  - Haliclorensin, a Novel Diamino Alkaloid from the Marine Sponge
      Haliclonatulearensis
AB  - Haliclorensin (1), a novel diamino alkaloid possessing an azacyclodecane ring,
      has been isolated from the sponge Haliclona tulearensis. Its structure was
      elucidated on the basis of spectroscopic data, as well as by comparison with
      gamma-amino azacycloalkanes.

PMID- 9548863
TI  - Quinoline Alkaloids: Synthesis of Pyrano
AB  - Polyphosphoric acid (PPA)-catalyzed cyclization of 2-ono-3
      vinylquinolinecarboxylic acid (1) yielded 3,4-dihydro-2,2-dimethyl-2H-pyrano[2,3
      b]quinoline (4). The same reaction of 4-methoxy-2-oxo-3-vinylquinolinecarboxylic
      acid (1g) afforded 4-methoxy-2,2-dimethylpyrano[2,3-b]quinoline (4g), which on
      hydrolysis with ethanolic hydrochloric acid gave khaplofoline (5). The Prevost
      reaction of 4-methoxy-3-prenylquinolin-2-one (6) using I2/HgO in acetic acid
      yielded 4-methoxy-2-isopropylfuro[2,3-b]quinoline (7). Compound 7 on reduction
      with H2/Pd-C followed by N-methylation and de-O-methylation afforded lunacrine
      (10a). A similar reaction sequence on 6b gave demethoxylunacrine (10b).

PMID- 9548864
TI  - The Synthesis of Phycopsisenone, a New Phenolic Secondary Metabolite from the
      Sponge Phycopsis sp.
AB  - A short first total synthesis of phycopsisenone (1) utilizing microwave
      irradiation-induced aldol condensation and TiCl4-catalyzed reaction of silyl enol
      ether (3) with acetone as key steps has been achieved in 29.4% overall yield.

PMID- 9548865
TI  - Lathyrus saponin, a new trisaccharide glycoside from Lathyrus japonicus.
AB  - A new triterpenoid saponin, named Lathyrus saponin (3), was isolated from the
      whole plant of Lathyrus japonicus Willd. together with two known saponins,
      azukisaponins II (1) and V (2). as their methyl esters. The structure of 3 was
      determined to be soyasapogenol B 3-0-beta-D-glucopyranosyl(1-->2)-beta-D
      glucopyranosyl(1-->2)-beta-D-glu curonopyranoside on the basis of physicochemical
      and spectroscopic methods.

PMID- 9548866
TI  - Trichoflectin, a bioactive azaphilone from the ascomycete Trichopezizella
      nidulus.
AB  - Trichoflectin (1), a new azaphilone belonging to the deflectin series, 6-deoxy-7
      0-demethyl-3,4-anhydrofusarubin (2), and 6-deoxy-3,4-anhydrofusarubin (3) were
      isolated from submerged cultures of the ascomycete Trichopezizella nidulus. All
      compounds showed antimicrobial activity and inhibited dihydroxynaphthalene
      melanin biosynthesis in fungi. The structure of trichoflectin (1) was elucidated
      by spectroscopic methods.

PMID- 9548870
TI  - New Briarane Stecholide Diterpenes from the Indonesian Gorgonian Briareum sp.
AB  - The Indonesian gorgonian Briareum sp. has afforded two new briarane stecholide
      diterpenes: 2,9-diacetyl-2-debutyrylstecholide H (1) and 13-dehydroxystecholide J
      (2), the semisynthetic 2beta-acetoxy-2-(debutyryloxy)stecholide E acetate (3),
      which was isolated as a natural product for the first time, along with the known
      compounds stecholides I-M (4-8), stecholide A acetate (9), and stecholide C
      acetate (10). The structures of the new compounds were deduced by extensive NMR
      studies (1H, 13C, 1H-1H COSY, NOESY, HMQC, and HMBC) and FABMS data (HR and LR).
      Cytotoxic activity was found for the first time in stecholide L (7).

PMID- 9548871
TI  - Further Petroformynes from Both Atlantic and Mediterranean Populations of the
      Sponge Petrosia ficiformis
AB  - Five novel polyacetylenes (5-9) were isolated from two different populations of
      the sponge Petrosia ficiformis collected in the Mediterranean Sea and the
      Atlantic Ocean. Their structures were established by extensive NMR analysis and
      by comparison with known petroformynes.

PMID- 9548872
TI  - New Hydroxylated Withanolides from Salpichroa origanifolia
AB  - From the leaves of Salpichroa origanifolia three new withanolides,
      (20S,22R,24S,25S,26R)-5alpha,6alpha:22,26:24,25-triepoxy-15,26-dihydroxy-17(13-
      >18)-abeo-ergosta-2,13,15,17-tetraen-1-one (salpichrolide G, 1),
      (20S,22R,24S,25R)-5alpha,6alpha:22,26-diepoxy-24,25,26-trihydroxy-17(13-->18)
      abeo-ergosta-2,13,15,17-tetraen-1-one (salpichrolide H, 2), and (20S,22R,25S)
      5alpha,6alpha:22,26-diepoxy-25,26-dihydroxy-17(13-->18)-abeo-ergosta
      2,13,15,17,23-pentaen-1-one (salpichrolide I, 3), were isolated and characterized
      by spectroscopic methods and with the aid of molecular modeling. The latter two
      compounds were obtained as an epimeric mixture at C-26.

PMID- 9548873
TI  - Two novel compounds from Paeonia suffructicosa.
AB  - A new hexacyclic triterpenoid, mudanpinoic acid A (1), and a new gallic acid
      glycoside, mudanoside B (2), along with nine known compounds--benzoic acid,
      resacetophenone, paeoniflorigenone, beta-sitosterol, betulinic acid, oleanoic
      acid, quercetin, beta-sitosterol-beta-D-glucoside, and trans-caffeic acid stearyl
      ester-were isolated from the dried root cortex of Paeonia suffruticosa. The
      structures of the novel compounds were elucidated on the basis of spectral
      methods, and that of compound 1 was confirmed by X-ray crystallographic analysis.

PMID- 9548874
TI  - Modified Monoterpenes from Biotransformation of (-)-Isopiperitenone by Suspension
      Cell Culture of Mentha piperita
AB  - The biotransformation of (-)-(4R)-isopiperitenone (1) by suspension cell culture
      of Mentha piperita yielded three new hydroxylated derivatives, 4-6, and two new
      epoxidized derivatives, 7 and 8. (-)-7-Hydroxyisopiperitenone (2) and its
      glucoside were previously isolated from the culture. The structures of 4-8 were
      elucidated using spectral methods, and their absolute stereochemistry was
      established by NMR experiments and correlation with compounds of known
      configuration.

PMID- 9548875
TI  - Four new bioactive lobane diterpenes of the soft coral Lobophytum pauciflorum
      from Mindoro, Philippines.
AB  - The marine soft coral Lobophytum pauciflorum collected from Mindoro Island,
      Philippines, yielded four new lobane diterpene derivatives: the acetate congeners
      of epoxylobatrienol and lobatrienediol (2 and 7, respectively), a methoxyl
      congener of lobatetraene (10), and an oxepin congener of lobatrienetriol (11),
      and six known derivatives (1, 3-6, and 8). The structures of the new compounds
      were unambiguously established on the basis of NMR spectroscopic (1H, 13C, COSY,
      1H-detected direct, and long-range 13C-1H correlations) and mass spectrometric
      (EIMS) data. All of the compounds were active against the phytopathogenic fungus
      Cladosporium cucumerinum. Compound 1 was found to be active against the Gram
      positive bacteria Bacillus subtilis and the yeast Saccharomyces cerevisiae. The
      isolated lobane diterpenes were also active in the brine shrimp lethality test.
      In the latter bioassay, compounds 8 and 10 were the most active congeners with
      LC50's of 0.64 and 4.18 micrograms/mL, respectively.

PMID- 9548876
TI  - Isolation of a New Fumonisin from Fusarium moniliforme Grown in Liquid Culture
AB  - A new fumonisin, iso-fumonisin B1 (iso-FB1, 1), has been isolated from liquid
      cultures of the fungus Fusarium moniliforme (Sheldon) NRRL 13616. On the basis of
      its spectroscopic data, its structure has been determined to differ from that of
      fumonisin B1 only in the presence of a hydroxyl function at C-4 instead of C-5.

PMID- 9548877
TI  - New Sulfated Polyhydroxysteroids from the Antarctic Ophiuroid Astrotomaagassizii
AB  - Three new and two known sulfated steroidal polyols have been isolated from the
      Antarctic ophiuroid Astrotoma agassizii. All of the new steroids possess a
      terminal isopropenyl group and a C-21 sulfoxy moiety in the side chain but differ
      in the steroidal nuclei. The structures of these new steroids were established
      from spectral and chemical correlations with related steroids as (20R)-cholesta
      5,24-diene-2beta,3alpha,21-triol 2,21-disulfate (1), (20R)-5alpha-cholest-24-ene
      2beta,3alpha,21-triol 3,21-disulfate (3), and (20R)-cholesta-5,24-diene
      2alpha,3alpha,4beta,21-tetrol 3,21-disulfate (5). Analysis of the nonsulfated
      sterol fraction has shown the presence of cholest-5-en-3beta-ol, cholesta-5,24
      dien-3beta-ol and (22E) cholesta-5,22-dien-3beta-ol as the major sterols.

PMID- 9548878
TI  - A New Norlupene from the Leaves of Melaleuca leucadendron
AB  - A new lupane-type nortriterpene and 13 known compounds were isolated from the
      leaves of Melaleuca leucadendron L. Based on chemical and spectral methods, the
      structure of the new compound was elucidated as 28-norlup-20(29)-ene-3beta,17beta
      diol, while the known compounds were identified as (2E,6E)-farnesol, phytol,
      squalene, alloaromadendrene, ledene, palustrol, viridiflorol, ledol,
      betulinaldehyde, betulinic acid, 3beta-acetyl-lup-20(29)-en-28-oic acid, 3-oxolup
      20(29)-en-28-oic acid, and platanic acid.

PMID- 9548879
TI  - New Quinoid Glycosides from Forsythia suspensa
AB  - Three novel compounds, suspenolic acid (1), forsythenside A (2), and
      forsythenside B (3), have been isolated from the fruits of Forsythia suspensa.
      Their structures were elucidated by spectral methods and chemical reactions.

PMID- 9548880
TI  - Conrauinones A and B, Two New Isoflavones from Stem Bark of Millettia conraui1
AB  - Two new isoflavones, named conrauinones A (1) and B (2), have been isolated from
      the stem bark of Millettia conraui, in addition to known 5-methoxydurmillone. The
      structures of the new compounds were determined by spectroscopic analysis
      including 2D NMR techniques as 5,6,2'-trimethoxy-4',5'-(methylenedioxy)-2",2"
      dimethylpyrano[5",6":7,8]isoflavone (1) and 6-methoxy-3',4'-(methylenedioxy)-7-O
      [(E)-3",7"-dimethyl-7"-ol-2",5"-octadienyl]isoflavone (2).

PMID- 9548881
TI  - A new lysine derivative and new 3-bromopyrrole carboxylic acid derivative from
      two marine sponges.
AB  - A novel lysine derivative, 1, has been isolated from the marine sponge Axinyssa
      terpnis, in addition to 4alpha-isocyanogorgon-11-ene and related compounds (2-4).
      From the marine sponge Axinella carteri, the new 3-bromopyrrole carboxylic acid
      derivative, 5, was obtained along with the known compounds aldisin (6) and 2
      bromoaldisin (7). Both sponges were collected from Chuuk Atoll, Federated States
      of Micronesia. The compounds were characterized by spectroscopic and chemical
      methods.

PMID- 9548882
TI  - Two New Dichromenes from Evodia lepta
AB  - Two new dichromenes, 1 and 2, were isolated from the aerial parts of Evodia
      lepta. Their structures were determined by spectroscopic analysis.

PMID- 9548883
TI  - Pyrrolidinoindoline Alkaloids from Psychotria colorata1
AB  - Fractionation of an alkaloid extract of Psychotria colorata flowers led to the
      isolation of six alkaloids, identified by UV, 1D and 2D NMR, and MS as (-)
      calycanthine, isocalycanthine, (+)-chimonanthine, hodgkinsine, quadrigemine C,
      and a new alkaloid (1), whose structure was deduced by X-ray analysis to be (8
      8a),(8'-8'a)-tetradehydroisocalycanthine 3a(R), 3'a(R).

PMID- 9548884
TI  - Synthesis and Stereochemistry of Axinastatin 4
AB  - Axinastatin 4 from a marine sponge was synthesized by high-dilution BOP-Cl
      cyclization of Trp-Val-Pro-Leu-Thr-Pro-Leu in 94% yield (only 2.5% at normal
      dilution), showing the configurations of the last three amino acids to be S.
      Synthetic axinastatin 4 was devoid of cytostatic activity.

PMID- 9548885
TI  - 18-nor-Abietatrienes from the Cones of Larix kaempferi
AB  - Two novel norditerpenediols, 18-nor-abieta-8,11,13-triene-4,15-diol (1) and 18
      nor-abieta-8,11,13-triene-4,7alpha-diol (2), were isolated from the cones of
      Larix kaempferi, together with two known diterpenes, abieta-8,11,13-triene-15,18
      diol and abieta-8,11,13-triene-7alpha,18-diol. The structures of 1 and 2 were
      determined on the basis of chemical and spectral evidence.

PMID- 9548886
TI  - Isohelianol: A 3,4-seco-Triterpene Alcohol from Sasanqua Oil
AB  - The structure of isohelianol isolated from the seeds of Camellia sasanqua Thunb.
      was established to be 3,4-seco-19(10-->9)-abeo-8alpha,9beta,10alpha-eupha-4,24
      dien-3-ol (1) on the basis of spectroscopic methods.

PMID- 9548887
TI  - Dioflorin, a Minor Flavonoid from Dioclea grandiflora
AB  - Dioflorin (1) was isolated as a minor constituent from the rootbark of Dioclea
      grandiflora, the crude extract of which demonstrated analgesic activity. The
      structure of 1 has been determined to be 5,7,2'-trihydroxy-8-methoxy-6-(3-methyl
      2-butenyl)flavanone on the basis of spectral analysis.

PMID- 9548888
TI  - Isolation and Structural Elucidation of Two Plant Ecdysteroids, Gerardiasterone
      and 22-Epi-20-hydroxyecdysone
AB  - Two minor plant ecdysteroids, 22-epi-20-hydroxyecdysone (1) and gerardiasterone
      (2), were isolated from Serratula tinctoria L. (Compositae). The first compound,
      a new natural product, was characterized by an unusual stereochemistry at C-22
      (i.e., 22S). The second compound was identified as (20R,23S)-20,23
      dihydroxyecdysone, a compound previously isolated from the Zooanthid Gerardia
      savaglia.

PMID- 9548890
TI  - Atmospheric pressure ionization LC/MS/MS techniques for drug disposition studies.

PMID- 9548891
TI  - Human intestinal permeability.
AB  - This review focuses on permeability measurements in humans, briefly discussing
      different perfusion techniques, the relevance of human Peff values, and various
      aspects of in vivo transport mechanisms. In addition, human Peff values are
      compared with corresponding data from three preclinical transport models. The
      regional human jejunal perfusion technique has been validated in several
      important ways. One of the most important findings is that there is a good
      correlation between the measured human effective permeability values and the
      extent of absorption of drugs in humans determined by pharmacokinetic studies.
      Estimations of the absorption half-lives from the measured Peff agree very well
      with the time to maximal amount of the dose absorbed achieved after an oral dose
      in humans. We have also shown that it is possible to determine the Peff for
      carrier-mediated transported compounds and to classify them according to the
      proposed biopharmaceutical classification system (BCS). Furthermore, human in
      vivo permeabilities can be predicted using preclinical permeability models, such
      as in situ perfusion of rat jejunum, the Caco-2 model, and excised intestinal
      segments in the Ussing chamber. The permeability of passively transported
      compounds can be predicted with a particularly high degree of accuracy. However,
      special care must be taken for drugs with a carrier-mediated transport mechanism,
      and a scaling factor has to be used. Finally, the data obtained in vivo in humans
      emphasize the need for more clinical studies investigating the effect of
      physiological in vivo factors and molecular mechanisms influencing the transport
      of drugs across the intestinal and as well as other membrane barriers. It will
      also be important to study the effect of antitransport mechanisms (multidrug
      resistance, MDR), such as efflux by P-glycoprotein(s) and gut wall metabolism,
      for example CYP 3A4, on bioavailability.

PMID- 9548892
TI  - Role of plasma lipoproteins in modifying the biological activity of hydrophobic
      drugs.
AB  - The plasma lipoprotein distribution of potential drug candidates is not commonly
      studied. For some hydrophobic drug candidates, attainment of similar plasma free
      drug levels has not been associated with uniform production of pharmacological
      activity in different animal species. It is well-known that plasma lipoprotein
      lipid profiles vary considerably between different animal species. In addition,
      human disease states can significantly influence plasma lipoprotein profiles,
      resulting in altered therapeutic outcomes. Current research has shown that
      lipoprotein binding of drug compounds can significantly influence not only the
      pharmacological and pharmacokinetic properties of the drug, but the relative
      toxicity as well. Elucidation of drug distribution among plasma lipoproteins is
      expected to yield valuable insight into factors governing the pharmacological
      activity and potential toxicity of the drug. This paper will present an
      historical perspective and summarize the latest research in the area of
      lipoprotein-drug interactions.

PMID- 9548893
TI  - Preparation, characterization, and evaluation of miconazole-cyclodextrin
      complexes for improved oral and topical delivery.
AB  - The solubility of miconazole in water increased in the presence of cyclodextrins
      (CDs). The apparent K1:1 values calculated from the phase solubility diagrams of
      gamma-CD, hydroxypropyl-beta-CD, alpha-CD, hydroxyethyl-beta-CD, hydroxypropyl
      gamma-CD, and beta-CD were 695 +/- 39.6, 363 +/- 34.1, 333 +/- 18.5, 312 +/-
      31.0, 305 +/- 27.6, and 293 +/- 17.6 M(-1), respectively. Solid 1:1 molar
      complexes were prepared by freeze-drying and kneading and characterized by UV
      spectroscopy, differential scanning calorimetry, and electron microscopy. The
      dissolution rate increased to 28-255-fold and the solubility to 9-55-fold. Oral
      bioavailability in rats increased to 2.3-fold by complexation with hydroxypropyl
      beta-CD. Human cadaver skin retained 2.6-fold more drug from the miconazole/alpha
      CD complex and hairless mice skin retained 8.4-fold more drug from the HP-beta-CD
      complex than from miconazole solution alone in 24 h.

PMID- 9548894
TI  - Intestinal peptide and protein delivery: novel bioadhesive drug-carrier matrix
      shielding from enzymatic attack.
AB  - We have been developing a novel bioadhesive drug-carrier matrix that protects
      embedded therapeutic peptides and proteins from degradation by the most abundant
      intestinal proteases. Increasing amounts of the Bowman-Birk inhibitor (BBI) were
      thereby covalently linked to chitosan-EDTA. The bioadhesive properties of the
      resulting polymer-BBI conjugates and their inhibitory effect toward trypsin (EC
      3.4.21.4), chymotrypsin (EC 3.4.21.1), elastase (3.4.21.36), carboxypeptidase A
      (EC 3.4.17.1), and aminopeptidase N (EC 3.4.11.2) were evaluated in vitro.
      Whereas unmodified chitosan-EDTA exhibited under our experimental conditions an
      adhesive strength of 54.4 +/- 7.7 mN, it was determined to be 21.0 +/- 3.8 mN for
      the comparably most adhesive polymer-BBI conjugate (mean +/- SD; n = 5). All
      polymer-BBI conjugates showed a strong inhibitory activity toward the serine
      proteases trypsin and chymotrypsin. However, the protective effect toward
      elastase was markedly lower. Due to the high binding affinity of chitosan-EDTA
      toward zinc, which represents an essential cofactor for carboxypeptidase A and
      aminopeptidase N, all polymer-BBI conjugates displayed additionally a strong
      protective effect toward these exopeptidases. The novel bioadhesive polymer-BBI
      conjugates described in this study seem to be very useful drug-carrier matrixes
      in overcoming the enzymatic barrier to orally administered peptide and protein
      drugs.

PMID- 9548895
TI  - Incorporation of drugs for the treatment of substance abuse into pigmented and
      nonpigmented hair.
AB  - Hair analysis for drugs may be useful for the long-term monitoring of recidivism
      and treatment compliance. L-alpha-Acetylmethadol, buprenorphine, and methadone
      are drugs that are used for the treatment of substance abuse. The purpose of this
      study was to study the relationship between dose, plasma concentration, hair
      concentration, and hair pigmentation for these compounds and their major
      metabolites in an animal model. Male Long-Evans rats received either L-alpha
      acetylmethadol (1 and 3 mg/kg; n = 6), buprenorphine (1 and 3 mg/kg; n = 5), or
      methadone (4 and 8 mg/kg; n = 5) by intraperitoneal injection daily for 5 days.
      Fourteen days after beginning drug administration, newly grown hair was collected
      and analyzed for either L-alpha-acetylmethadol and two metabolites (L-alpha
      acetyl-N-normethadol and L-alpha-acetyl-N,N-dinormethadol), methadone and two
      metabolites (D,L-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium and D,L-2-ethyl-5
      methyl-3,3-diphenyl-1-pyrroline), or buprenorphine and one metabolite
      (norbuprenorphine). The plasma time course (AUC) for each compound was also
      determined after a single administration of each drug at the specified doses.
      There was an approximate dose-dependent increase in measured hair concentration
      of each parent drug in pigmented hair. The concentrations of L-alpha
      acetylmethadol, methadone, and buprenorphine in nonpigmented hair were
      significantly less than that measured in pigmented hair at either the high or low
      dose. The metabolites L-alpha-acetyl-N-normethadol and D,L-2-ethyl-1,5dimethyl
      3,3-diphenylpyrrolinium were detected at lower concentrations than their
      respective parent compounds (L-alpha-acetylmethadol or methadone) in pigmented
      hair. However, the L-alpha-acetyl-N,N-dinormethadol metabolite concentrations in
      pigmented hair were significantly greater than those of the parent drug after
      either the low or the high L-alpha-acetylmethadol dose. These data demonstrate
      that L-alpha-acetylmethadol, methadone, buprenorphine, and metabolites are
      distributed into hair in a dose-related manner with a preference for pigmented
      hair.

PMID- 9548896
TI  - Comparative biomembrane permeation of tacrine using Yucatan minipigs and domestic
      pigs as the animal model.
AB  - Tacrine (THA), a centrally acting acetylcholine-esterase inhibitor, is presently
      administered perorally for the treatment of Alzheimer's disease (AD). However,
      its low bioavailablity (i.e., 17%) and short half-life (2-4 h) demand the search
      for alternative routes of administration. The primary objective of this study was
      to assess the potential of absorptive mucosae and skin as routes for improving
      the systemic delivery of THA. The Yucatan minipig, which has been used
      increasingly in biomedical research as a useful model for humans, and the
      domestic pig, which is available at low cost, were evaluated for their
      suitability as animal model. Permeation kinetics of THA across various absorptive
      mucosae (nasal, buccal, sublingual, and rectal) of both species of swine were
      studied in the hydrodynamically well-calibrated Valia-Chien permeation cells. For
      comparison, permeation through various intestinal segments (duodenum, jejunum,
      and ileum) was also measured. Results indicated that both species display similar
      permeation characteristics. However, the data obtained for the domestic pigs
      shows lower intra- and inter-animal variabilities than that of the Yucatan
      minipigs. The nasal mucosa was found to have the highest permeability, while the
      buccal mucosa had the lowest among the absorptive mucosae. The intrinsic
      permeabilities and diffusivity of THA across the four absorptive mucosae were not
      significantly different between species but lower than that for the intestinal
      segments for both species. Using dorsal skin as the model, the skin permeation of
      THA was also investigated and the results indicated that the domestic swine has a
      significantly higher skin permeability than the Yucatan minipig, with more than a
      2-fold difference in intrinsic permeabilities. The intrinsic permeability,
      partition coefficient, and diffusivity for domestic pig skin are very similar to
      that for human cadaver skin. Considering the potential of bypassing the hepatic
      "first-pass" elimination, the absorptive mucosae may be useful routes for
      systemic delivery of THA to achieve improved bioavailability. With additional
      advantages of lower variability, ease of membrane excision, good accessibility,
      and lower cost, it is concluded that the domestic swine is a better animal model
      than the Yucatan minipig for preclinical studies on the systemic delivery of
      tacrine.

PMID- 9548898
TI  - Migration of adhesive and nonadhesive particles in the rat intestine under
      altered mucus secretion conditions.
AB  - The migration rate of adhesive (polycarbophil) and nonadhesive (Eudragit RL-100)
      particles was studied in the small and large intestine of the anesthetized rat
      under altered mucus secretion conditions accomplished by cholinergic stimulation
      (a previously developed in situ model which distinctly accounts for the effect of
      regional changes in mucus turnover rate on mucoadhesion in the digestive tube of
      the rat). It was found that in the proximal jejunum the relative recovery time
      (RRT) of adhesive particles, but not nonadhesive particles, was decreased by
      carbachol stimulation. However, adhesive particles agglomerated a short while
      after their administration into this organ. In the colon RRT of both adhesive and
      nonadhesive particles decreased in a similar manner as the mucus secretion
      increased. It is concluded that, in the rat, interactions between intestinal
      mucus layer and adhesive and nonadhesive particles are similar. The corresponding
      similarity in the intestinal transit time for both types of particles raises
      doubts about the advantage of nonspecific adherence in the design of oral
      prolonged-release dosage forms.

PMID- 9548897
TI  - Effects of various protease inhibitors on the stability and permeability of [D
      Ala2,D-Leu5]enkephalin in the rat intestine: comparison with leucine enkephalin.
AB  - The effects of various protease inhibitors on the stability of leucine enkephalin
      (Leu-Enk) and [D-Ala2,D-Leu5] enkephalin (DADLE) were investigated, and the
      permeability of these peptides was also examined in an in vitro Ussing chamber.
      Captopril, thiorphan, bacitracin, bestatin, puromycin, amastatin, and sodium
      glycocholate (Na-GC) were chosen as protease inhibitors. Regional differences in
      the stability of Leu-Enk and DADLE were observed, and the rank order of the
      stability of these peptides was colon > duodenum > ileum > jejunum. Na-GC,
      amastatin, and puromycin were effective protease inhibitors for improving the
      stability of these peptides, although captopril and thiorphan did not improve the
      stability of Leu-Enk. In the transport studies, Leu-Enk did not cross the
      intestinal membrane in the absence of protease inhibitors, but its transport was
      improved in the presence of Na-GC. In addition, Na-GC, amastatin, and puromycin
      improved the permeability of DADLE in both jejunum and colon, while the
      permeability of DADLE was not improved by the addition of captopril, thiorphan,
      and bestatin. Furthermore, the permeability of 6-carboxyfluorescein, a poorly
      absorbable and stable compound, was also improved in the presence of Na-GC and
      bacitracin at a concentration of 10 mM. These findings indicated that amastatin,
      puromycin, and Na-GC at a concentration of 0.5 mM might increase the permeability
      of DADLE due to the improved stability of DADLE in the donor site. However, Na-GC
      and bacitracin at a concentration of 10 mM had absorption-enhancing activities
      which might be also related to the enhanced permeability of DADLE across the
      intestinal membrane.

PMID- 9548899
TI  - Stereoselective inhibition by the diastereomers quinidine and quinine of uptake
      of cardiac glycosides into isolated rat hepatocytes.
AB  - The pharmacokinetic interaction between quinidine and digoxin in patients is well
      known, in general requiring a dose reduction of digoxin in patients concomitantly
      treated with quinidine. Quinine, the diastereomer of quinidine, has not been as
      extensively studied in this respect. In addition to an interaction with the renal
      clearance of digoxin by quinidine, both diastereomers have been reported to
      inhibit the biliary clearance of digoxin in man. To further investigate the
      mechanisms of these hepatobiliary transport interactions at the cellular level,
      we compared the effects of quinidine and quinine, as well as of the calcium
      antagonist verapamil, on the uptake of digoxin and ouabain in isolated rat
      hepatocytes. Initial uptake rates of digoxin and ouabain were determined in the
      presence of various concentrations of quinine and quinidine. A concentration
      dependent inhibition of the cellular uptake of both cardiac glycosides by quinine
      and quinidine was found, quinine being a more potent inhibitor than quinidine.
      Our results indicate a stereoselective inhibition of the hepatocellular uptake by
      the two diastereomers quinidine and quinine, the latter being about equipotent to
      verapamil. This unequal inhibitory potency of the two basic drugs was detected
      earlier in oocyte studies with the cloned organic cation transporter OCT1.

PMID- 9548900
TI  - Synergistic effect of iontophoresis and a series of fatty acids on LHRH
      permeability through porcine skin.
AB  - The effect of chemical penetration enhancers (e.g., fatty acids) in combination
      with iontophoresis was examined on the in vitro permeability of luteinizing
      hormone releasing hormone (LHRH) through porcine skin. Porcine epidermis was
      pretreated with either ethanol (EtOH) or 10% fatty acid/EtOH. The permeability
      coefficient of LHRH was significantly (p < 0.05) greater through EtOH, lauric
      acid/EtOH, palmitic acid/EtOH, oleic acid/EtOH, linoleic acid/EtOH, and linolenic
      acid/EtOH treated epidermis than the control (untreated epidermis). Iontophoresis
      further enhanced the permeability of LHRH (p < 0.05) through enhancer-pretreated
      epidermis in comparison with corresponding passive permeability. Among saturated
      fatty acids tested, 10% palmitic acid/iontophoresis showed the highest
      permeability coefficient [(59.52 +/- 2.40) x 10(-4) cm/h], which was
      approximately 16-fold higher than that of the control [(3.57 +/- 0.41) x 10(-4)
      cm/h]. Unsaturated cis-octadecenoic acids were more effective penetration
      enhancers when compared with octadecanoic acid. Among cis-octadecenoic acids in
      combination with EtOH, the greater iontophoretic permeability coefficient [(59.18
      +/- 12.43) x 10(-4) cm/h] was obtained through linolenic acid treated epidermis,
      which was significantly greater (p < 0.05) than through saturated octadecanoic
      acid treated epidermis [(29.08 +/- 3.18) x 10(-4) cm/h]. Also, pretreatment of
      epidermis with 5% linolenic acid/propylene glycol (PG) resulted in greater (p <
      0.05) iontophoretic flux of LHRH in comparison to 5% linolenic acid/EtOH.
      Furthermore, increases in the degree of unsaturation in octadecenoic acids did
      not produce corresponding increases in the degree of enhancement. Reversibility
      studies revealed that the postrecovery passive flux of LHRH through 5% linolenic
      acid in combination with EtOH or PG/iontophoresis treated epidermis was
      significantly (p < 0.05) reduced than the prerecovery value but could not
      completely recover to the baseline flux (i.e., flux of LHRH through untreated
      epidermis).

PMID- 9548901
TI  - Physiologically relevant one-compartment pharmacokinetic models for skin. 1.
      Development of models.
AB  - Many studies have used pharmacokinetic (compartment) models for skin to predict
      or analyze absorption of chemicals through skin. In these studies, several
      different definitions of the rate constants were used. The purpose of this study
      was to develop a general procedure for relating compartment model rate constants
      to dermal absorption parameters, such as permeability and partition coefficients,
      and to assess whether different definitions of the rate constants produce
      different results. Rate constant expressions were developed by requiring a one
      compartment model to match a one-membrane model at specific conditions. Because a
      membrane model contains more information than a compartment model, a compartment
      model cannot match the membrane model in all respects. Consequently, many
      compartment models (i.e., different definitions of the rate constants) can be
      developed which match the membrane model for different conditions. Using this
      procedure, 11 different compartment models were developed and compared to the
      membrane model for four different dermal absorption scenarios. The compartment
      model that most closely matches the membrane model depends on the specific
      exposure scenario and what is to be predicted. One of the new compartment models
      agrees reasonably well with the membrane model, for the cases considered.

PMID- 9548902
TI  - Physiologically relevant one-compartment pharmacokinetic models for skin. 2.
      Comparison of models when combined with a systemic pharmacokinetic model.
AB  - Transport of chemicals through skin is best modeled as passive diffusion through
      a membrane, but mathematical solutions for realistic conditions are cumbersome.
      Compartment models, representing skin as a stirred tank, are mathematically
      simpler but less physiologically relevant. In a previous paper, several different
      compartment models were developed assuming constant blood and vehicle
      concentrations. Here, five skin models (four of the previously described
      compartment models and one membrane model) are combined with a one-compartment
      systemic pharmacokinetic (PK) model to examine the effects of changing vehicle
      and blood concentrations and to clarify how differences between skin models
      affect the predicted systemic response. The skin-PK models were solved with the
      same input parameters (i.e., permeability coefficients, partition coefficients,
      skin thickness, and cutaneous blood flow rates) and compared for five different
      exposure scenarios. Because the models have different underlying assumptions,
      they do predict different results. For many exposure situations compartment
      models give acceptable results, with the most pronounced differences from the
      membrane model during short exposure times. Generally, the compartment model that
      most closely represents the membrane model was developed by forcing it to match
      the membrane model for conditions similar to those of the given exposure
      scenario.

PMID- 9548903
TI  - Freeze-drying of tert-butyl alcohol/water cosolvent systems: effects of
      formulation and process variables on residual solvents.
AB  - The objective of this study was to identify significant formulation and
      processing variables affecting levels of tert-butyl alcohol (TBA) and isopropyl
      alcohol (IPA) in freeze-dried solids prepared from TBA/water cosolvent systems.
      The variables examined were the physical state of the solute (crystalline vs
      amorphous), initial TBA concentration, freezing rate, cake thickness, and the
      temperature and duration of secondary drying. Sucrose and glycine were used as
      models for noncrystallizing and crystallizing solutes, respectively. The TBA
      concentration above which eutectic crystallization takes place was determined by
      differential scanning calorimetry. Model formulations were subjected to extremes
      of freezing rate by either dipping in liquid nitrogen or by slowly freezing on
      the shelf of a freeze-dryer. Dynamics of solvent loss during secondary drying was
      determined by withdrawing samples as a function of time at different shelf
      temperatures using a thief system. On the basis of these studies, the most
      important determinant of residual TBA level is the physical state of the solute.
      Freeze-dried glycine contained very low levels of residual TBA (0.01-0.03%)
      regardless of freezing rate or initial TBA concentration. For freeze-dried
      sucrose, residual TBA levels were approximately 2 orders of magnitude higher and
      were significantly affected by initial TBA concentration and freezing rate. For
      the sucrose/TBA/water system, relatively low residual TBA levels were obtained
      when the initial TBA level was above the threshold concentration for eutectic
      crystallization of TBA, whereas samples freeze-dried from solutions containing
      TBA concentrations below this threshold contained significantly higher levels of
      TBA. Residual IPA levels increased continuously with initial concentration of TBA
      in the sucrose/TBA/water system. Formulations of sucrose/TBA/water which were
      frozen rapidly contained residual TBA levels which were approximately twice those
      measured in the same formulation after slow freezing and drying under the same
      conditions. For the sucrose/TBA/water system, the temperature and time of
      secondary drying had only minimal influence on residual TBA in the freeze-dried
      solid. At low initial TBA concentrations (2%), residual TBA increases with
      increased cake thickness, perhaps because of the influence of depth of fill on
      effective freezing rate.

PMID- 9548904
TI  - Animal pharmacokinetics and interspecies scaling of Ro 25-6833 and related
      (lactamylvinyl)cephalosporins.
AB  - From a series of six (lactamylvinyl)cephalosporins, candidates for clinical
      evaluation were selected on the basis of their kinetic profile in animals and
      predicted pharmacokinetics in man. Exploratory pharmacokinetic studies with Ro 25
      6833 and five related cephalosporins were performed following intravenous
      administration to rats, dogs, and cynomolgus monkeys. All compounds were
      characterized by a high protein binding in rat, monkey, and human plasma (unbound
      fraction < or = 5%), whereas in dog plasma, protein binding was markedly lower.
      Accordingly, for most compounds, clearance was highest in dogs, and lowest in
      monkeys. Comparison of the renal clearance of unbound drug with creatinine
      clearance suggests a renal elimination of Ro 25-6833 by glomerular filtration in
      both rats and dogs (urinary excretion in monkey was not determined due to drug
      instability in monkey urine). All other compounds showed different renal
      excretion mechanisms in rats and dogs, thus making the validity of allometric
      scaling questionable. Unbound clearances in man were predicted by allometric
      scaling (Ro 25-6833 only) and by a correlation analysis of cephalosporin
      pharmacokinetics in monkey and man. Limitations of both methods are discussed.
      When Ro 25-6833 was later studied in man, the predicted pharmacokinetic data in
      man from both approaches were found to be in good agreement with the observed
      values.

PMID- 9548905
TI  - Solid-state characterization of two polymorphs of aspartame hemihydrate.
AB  - From the known crystal structure of aspartame hemihydrate, designated form 1, the
      theoretical powder X-ray diffraction (PXRD) pattern was calculated. This PXRD
      pattern differs significantly from that of the commercially available aspartame
      hemihydrate, which is therefore a different polymorph, designated form II. Form
      II transforms to form I during ball-milling or on heating for 30 min at 160
      degrees C in the presence of steam. The two polymorphs were compared by PXRD,
      differential scanning calorimetry, thermogravimetric analysis, Karl Fischer
      titrimetry, Fourier transform infrared (FTIR) absorption spectroscopy, 13C solid
      state nuclear magnetic resonance (SSNMR) spectroscopy, scanning electron
      microscopy, particle size analysis, and measurements of true density and
      intrinsic dissolution rate. Comparison of the 13C SSNMR and FTIR spectra of the
      two polymorphs suggests that the crystal structure of form II is less symmetric,
      with the side chains located in multiple environments. Although both hemihydrate
      polymorphs on heating in the absence of moisture dehydrate to a crystalline
      anhydrate, form I does so at a lower temperature, suggesting weaker interactions
      of water with aspartame molecules. At higher temperatures the anhydrate from both
      hemihydrate polymorphs yields 3-(carboxymethyl)-6-benzyl-2,5-dioxopiperazine
      (DKP) by a cyclization reaction for which the temperature, reaction enthalpy, and
      activation energy are very similar. Both hemihydrate forms, when in contact with
      liquid water, yield the 2.5-hydrate.

PMID- 9548906
TI  - Hydration and dehydration behavior of aspartame hemihydrate.
AB  - Previous studies have shown that aspartame in the solid state can exist as a
      hemihydrate which occurs in two different polymorphic forms (I and II). The
      present work shows that equilibration of either hemihydrate at 25 degrees C with
      water vapor at relative humidities > or = 58% or with liquid water produces a 2.5
      hydrate. Upon subjecting each of these crystalline hydrates to increasing
      temperature, the same crystalline anhydrate is formed which thermally cyclizes at
      a higher temperature to form the known compound 3-(carboxymethyl)-6-benzyl-2,5
      dioxopiperazine. The activation energy of the cyclization reaction appears to
      depend on the degree of crystallinity of the anhydrate that is formed at a lower
      temperature. On increasing the temperature of the 2.5-hydrate, a hemihydrate
      intervenes before the anhydrate is formed. This intervening hemihydrate is
      similar to the commercial form (II) of aspartame hemihydrate but exhibits greater
      amorphous character. The techniques employed were Karl Fischer titrimetry, powder
      X-ray diffractometry, differential scanning calorimetry, thermogravimetric
      analysis, solid-state 13C nuclear magnetic resonance spectroscopy, and Fourier
      transform infrared absorption spectroscopy.

PMID- 9548907
TI  - Inclusion complexation of propofol with 2-hydroxypropyl-beta-cyclodextrin.
      Physicochemical, nuclear magnetic resonance spectroscopic studies, and anesthetic
      properties in rat. trapani@ippo.uniba.it.
AB  - An aqueous formulations of propofol 1 can be prepared by solubilizing it in the
      presence of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD). This is potentially
      useful for parenteral administration of the drug. The aqueous solubility of 1
      linearly increased as a function of HP-beta-CD concentration and showed features
      of an AL type diagram. Thermodynamic parameters were obtained by using the
      temperature dependence of the stability constant at temperatures of between 25
      and 37 degrees C. The results indicate that complex formation is enthalpically,
      rather than entropically, driven and that it may involve van der Waals
      (dispersive) forces, rather than hydrophobic interactions. The structure of the
      inclusion complex propofol/HP-beta-CD was investigated in D2O, using 1H and 13C
      NMR spectroscopy. These studies revealed that the whole aromatic ring, as well as
      part of the isopropyl groups of the guest molecule, is located inside the HP-beta
      CD cavity, while the hydroxy group is located at the rim of the wider cavity end.
      The geometrical features of the inclusion complex 1-HP-beta-CD are confirmed by
      1D NOE difference spectra and molecular modeling experiments. The anesthetic
      activity in rat was investigated, and it was found that there are significant
      differences in induction time and sleeping time between 1 solubilized in the
      presence of HP-beta-CD and the formulation currently used (Diprivan), which is a
      1% w/v oil/water emulsion.

PMID- 9548908
TI  - Preparation of norfloxacin spherical agglomerates using the ammonia diffusion
      system.
AB  - Agglomerated crystals of norfloxacin were prepared by a spherical crystallization
      technique using the ammonia diffusion system (ADS). This technique makes it
      possible to agglomerate amphoteric drugs like norfloxacin, which cannot be
      agglomerated by conventional procedures. When an ammonia-water solution of
      norfloxacin is poured into an acetone dichloromethane mixture under agitation, a
      small amount of ammonia is liberated in the system. The ammonia-water solution
      plays a role both as a good solvent for norfloxacin and as a bridging liquid,
      allowing the crystals' collection to take place in one step. It has been proven
      that the agglomeration mechanism follows three steps: first acetone enters into
      the droplets of ammonia-water (this emulsion is formed because of the system
      characteristics); dissolved norfloxacin is consequently precipitated while the
      droplets collect the crystals; simultaneously, a part of the ammonia contained in
      the agglomerates diffuses to the outer organic solvent phase, thereby forming the
      norfloxacin spherical agglomerates. The correct selection of solvents has enabled
      us to obtain a suitable stable crystalline shape.

PMID- 9548909
TI  - Determination of the optimum mixing time for a mixture of lactose and colloidal
      silicon dioxide.
AB  - The homogeneity of a mixture of colloidal silicon dioxide (CSD) and lactose is
      examined by quantifying the dependence of the CSD content on the mixing time. CSD
      concentration is determined photometrically as a blue silica-molybdic complex.
      Its deviation from the expected content is taken to characterize the mixture
      quality and the optimum mixing time. The conformity of this result with the flow
      properties of the same mixture is studied by measuring the dependence of the
      angle of repose on the mixing time.

PMID- 9548910
TI  - Integration of in vitro data and brain weight in allometric scaling to predict
      clearance in humans: some suggestions.

PMID- 9548914
TI  - Protein folding dynamics: quantitative comparison between theory and experiment.
AB  - The development of a quantitative kinetic scheme is a central goal in mechanistic
      studies of biological phenomena. For fast-folding proteins, which lack
      experimentally observable kinetic intermediates, a quantitative kinetic scheme
      describing the order and rate of events during folding has yet to be developed.
      In the present study, the folding mechanism of monomeric lambda repressor is
      described using the diffusion-collision model and estimates of intrinsic alpha
      helix propensities. The model accurately predicts the folding rates of the wild
      type protein and five of eight previously studied Ala left and right arrow Gly
      variants and suggests that the folding mechanism is distributed among multiple
      pathways that are highly sensitive to the amino acid sequence. For example, the
      model predicts that the wild-type protein folds through a small number of
      pathways with a folding time of 260 micros. However, the folding of a variant
      (G46A/G48A) is predicted to fold through a large number of pathways with a
      folding time of 12 micros. Both folding times quantitatively agree with the
      experimental values at 37 degrees C extrapolated to 0 M denaturant. The
      quantitative nature of the diffusion-collision model allows for rigorous
      experimental tests of the theory.

PMID- 9548915
TI  - Rational design of novel antimicrobials: blocking purine salvage in a parasitic
      protozoan.
AB  - All parasitic protozoa obtain purine nucleotides solely by salvaging purine bases
      and/or nucleosides from their host. This observation suggests that inhibiting
      purine salvage may be a good way of killing these organisms. To explore this
      idea, we attempted to block the purine salvage pathway of the parasitic protozoan
      Tritrichomonas foetus. T. foetus is a good organism to study because its purine
      salvage depends primarily on a single enzyme, hypoxanthine-guanine-xanthine
      phosphoribosyltransferase (HGXPRTase), and could provide a good model for
      rational drug design through specific enzyme inhibition. Guided by the crystal
      structure of T. foetus HGXPRTase, we used structure-based drug design to identify
      several non-purine compounds that inhibited this enzyme without any detectable
      effect on human HGPRTase. One of these compounds, 4-[N-(3, 4
      dichlorophenyl)carbamoyl]phthalic anhydride (referred to as TF1), was selected
      for further characterization. TF1 was shown to be a competitive inhibitor of T.
      foetus HGXPRTase with respect to both guanine (in the forward reaction; Ki = 13
      microM) and GMP (in the reverse reaction; Ki = 10 microM), but showed no effect
      on the homologous human enzyme at concentrations of up to 1 mM. TF1 inhibited the
      in vitro growth of T. foetus with an EC50 of approximately 40 microM. This
      inhibitory effect was associated with a decrease in the incorporation of
      exogenous guanine into nucleic acids, and could be reversed by supplementing the
      growth medium with excess exogenous hypoxanthine or guanine. Thus, rationally
      targeting an essential enzyme in a parasitic organism has yielded specific enzyme
      inhibitors capable of suppressing that parasite's growth.

PMID- 9548916
TI  - Mapping the active sites of 3-phosphoglycerate kinase and glycerol kinase with
      monoammine chromium(III) ATP.
AB  - The 12 isomers of monoammine chromium(III) ATP have been used to probe the ATP
      binding sites of yeast 3-phosphoglycerate kinase and glycerol kinase from Candida
      mycoderma. Inhibition studies of 3-phosphoglycerate kinase show a dramatic
      decrease in isomer binding only when the ammonia is in the Delta axial facial
      anti position. This suggests an open site architecture with only one strong
      contact point between the coordination sphere and the enzyme surface. These
      results agree well with the computer modeling studies of bidentate chromium ATP
      into the nucleotide site determined by X-ray crystallography [McPhillips, T., et
      al. (1996) Biochemistry 35, 4118-4127]. Both methods describe an open site
      strongly supporting the validity of the inhibition studies. Inhibition studies of
      glycerol kinase show significant decreases in binding for all the tested ammonia
      positions, suggesting a closed site architecture with many contacts between the
      coordination sphere and the surface of the enzyme. This is in good agreement with
      X-ray studies [Hurley, T., et al. (1993) Science 259, 673-677] on the Escherichia
      coli glycerol kinase. Inhibition studies of hexokinase previously reported
      [Rawlings, J., et al. (1993) Biochemistry 32, 11204-11210] more closely resemble
      those of 3-phosphoglycerate kinase, suggesting the surprising result that however
      closely hexokinase and glycerol kinase are related structurally the site around
      the coordination sphere in hexokinase is functionally open like that of 3
      phosphoglycerate kinase.

PMID- 9548917
TI  - Characterization and functional role of the QH site of bo-type ubiquinol oxidase
      from Escherichia coli.
AB  - Cytochrome bo is a four-subunit terminal ubiquinol oxidase in the aerobic
      respiratory chain of Escherichia coli that vectorially translocates protons not
      only via directed protolytic reactions but also via proton pumping. Previously,
      we postulated that a bound quinone in the high-affinity quinone binding site (QH)
      mediates electron transfer from the low-affinity quinol oxidation site (QL) in
      subunit II to low-spin heme b in subunit I as an electron gate and a transient
      electron reservoir [Sato-Watanabe, M., Mogi, T., Ogura, T., Kitagawa, T.,
      Miyoshi, H., Iwamura, H., and Anraku, Y. (1994b) J. Biol. Chem. 269, 28908
      28912]. In the present study, we carried out screening of ubiquinone analogues
      using a bound ubiquinone-free enzyme (DeltaUbiA1) that has been isolated from a
      ubiquinone biosynthesis mutant, and identified PC24 (2-chloro-4, 6
      dinitrophenol), PC32 (2,6-dibromo-4-cyanophenol), and PC52 (2-isopropyl-5-methyl
      4,6-dinitrophenol) as potent QH site inhibitors. PC15 (2,6-dichloro-4
      nitrophenol) and PC16 (2, 6-dichloro-4-dicyanovinylphenol), potent QL site
      inhibitors, did not exhibit such a selective inhibition of the QH site. Binding
      studies using the air-oxidized DeltaUbiA enzyme showed that PC32 and PC52 have 4-
      to 7-fold higher affinity than ubiquinone-1. Reconstitution of the QH site with
      PC32 and PC52 resulted in a decrease of the apparent Vmax value to 1/7 and 1/3,
      respectively, of the control activity. These findings suggest that structural
      features of the QL and QH sites are different, and provide further support for
      the involvement of the QH site in intramolecular electron transfer and facile
      oxidation of quinols at the QL site.

PMID- 9548918
TI  - Reaction between S-nitrosothiols and thiols: generation of nitroxyl (HNO) and
      subsequent chemistry.
AB  - S-Nitrosothiols have been implicated to play key roles in a variety of
      physiological processes. The potential physiological importance of S
      nitrosothiols prompted us to examine their reaction with thiols. We find that S
      nitrosothiols can react with thiols to generate nitroxyl (HNO) and the
      corresponding disulfide. Further reaction of HNO with the remaining S
      nitrosothiol and thiol results in the generation of other species including NO,
      sulfinamide, and hydroxylamine. Mechanisms are proposed that rationalize the
      observed products.

PMID- 9548919
TI  - Methionine synthase exists in two distinct conformations that differ in
      reactivity toward methyltetrahydrofolate, adenosylmethionine, and flavodoxin.
AB  - Methionine synthase (MetH) from Escherichia coli catalyzes the synthesis of
      methionine from homocysteine and methyltetrahydrofolate via two methyl transfer
      reactions that are mediated by the endogenous cobalamin cofactor. After binding
      both substrates in a ternary complex, the enzyme transfers a methyl group from
      the methylcobalamin cofactor to homocysteine, generating cob(I)alamin enzyme and
      methionine. The enzyme then catalyzes methyl transfer from methyltetrahydrofolate
      to the cob(I)alamin cofactor, forming methylcobalamin cofactor and
      tetrahydrofolate prior to the release of both products. The cob(I)alamin form of
      the enzyme occasionally undergoes oxidation to an inactive cob(II)alamin species;
      the enzyme also catalyzes its own reactivation. Electron transfer from reduced
      flavodoxin to the cob(II)alamin cofactor is thought to generate cob(I)alamin
      enzyme, which is then trapped by methyl transfer from adenosylmethionine to the
      cobalt, restoring the enzyme to the active methylcobalamin form. Thus the enzyme
      is potentially able to catalyze two methyl transfers to the cob(I)alamin
      cofactor: methyl transfer from methyltetrahydrofolate during primary turnover and
      methyl transfer from adenosylmethionine during activation. It has recently been
      shown that methionine synthase is constructed from at least four separable
      regions that are responsible for binding each of the three substrates and the
      cobalamin cofactor, and it has been proposed that changes in positioning of the
      substrate binding regions vis-a-vis the cobalamin binding region could allow the
      enzyme to control which substrate has access to the cofactor. In this paper, we
      offer evidence that methionine synthase exists in two different conformations
      that interconvert in the cob(II)alamin oxidation state. In the primary turnover
      conformation, the enzyme reacts with homocysteine and methyltetrahydrofolate but
      is unreactive toward adenosylmethionine and flavodoxin. In the reactivation
      conformation, the enzyme is active toward adenosylmethionine and flavodoxin but
      unreactive toward methyltetrahydrofolate. The two conformations differ in the
      susceptibility of the substrate-binding regions to tryptic proteolysis. We
      propose a model in which conformational changes control access to the cobalamin
      cofactor and are the primary means of controlling cobalamin reactivity in
      methionine synthase.

PMID- 9548920
TI  - Electrostatic evaluation of the signature motif (H/V)CX5R(S/T) in protein
      tyrosine phosphatases.
AB  - The catalytic activity of protein-tyrosine phosphatases (PTPs) is mediated by a
      cysteine side chain which carries out a nucleophilic attack initiating the
      phosphate cleavage. Experimentally, it has been observed that the active site
      cysteine has a remarkably low pKa. In the present study, we have investigated the
      origin of the low pKa by analyzing the electrostatic properties of four different
      protein-tyrosine phosphatases: Yersinia PTP (bacteria), PTP1B (human), VHR
      (human), and low molecular weight phosphatase (bovine). These phosphatases have
      very low sequence homology and show very low structural similarity. However, they
      share a common active site motif [the (H/V)CX5R(S/T) sequence] which adopts a
      unique loop structure. We have applied the so-called single site titration
      method, which is based on the Poisson-Boltzmann methodology, to (i) study the
      influence of the architecture of the (H/V)CX5R(S/T) loop on the pKa of the active
      cysteine and (ii) examine which parts of the active site region stabilize the
      ionized form of the cysteine. Our results indicate that the architecture of the
      (H/V)CX5R(S/T) loop has a major impact on the low pKa of the active cysteines.
      The orientation of the microdipoles generated by the partial charges of the
      backbone atoms (i.e., the CONHCalpha atoms) is essential for maintaining the low
      pKa. Further, the electrostatic field generated by these microdipoles has a
      larger impact than the electrostatic dipole generated by the central alpha-helix.
      Interactions of the active cysteine with other ionizable side chains play a minor
      role in stabilizing the thiolate anion. The only ionizable side chain
      significantly influencing the pKa of the active site cysteine is the arginine,
      which is an important part of the consensus sequence.

PMID- 9548921
TI  - Loop closure and intersubunit communication in tryptophan synthase.
AB  - Crystal structures of wild-type tryptophan synthase alpha2beta2 complexes from
      Salmonella typhimurium were determined to investigate the mechanism of allosteric
      activation of the alpha-reaction by the aminoacrylate intermediate formed at the
      beta-active site. Using a flow cell, the aminoacrylate (A-A) intermediate of the
      beta-reaction () was generated in the crystal under steady state conditions in
      the presence of serine and the alpha-site inhibitor 5-fluoroindole propanol
      phosphate (F-IPP). A model for the conformation of the Schiff base between the
      aminoacrylate and the beta-subunit cofactor pyridoxal phosphate (PLP) is
      presented. The structure is compared with structures of the enzyme determined in
      the absence (TRPS) and presence (TRPSF-IPP) of F-IPP. A detailed model for
      binding of F-IPP to the alpha-subunit is presented. In contrast to findings by
      Hyde et al. [(1988) J. Biol. Chem. 263,17857-17871] and Rhee et al. [(1997)
      Biochemistry 36, 7664-7680], we find that the presence of an alpha-site alone
      ligand is sufficient for loop alphaL6 closure atop the alpha-active site. Part of
      this loop, alphaThr183, is important not only for positioning the catalytic
      alphaAsp60 but also for coordinating the concomitant ordering of loop alphaL2
      upon F-IPP binding. On the basis of the three structures, a pathway for
      communication between the alpha- and beta-active sites has been established. The
      central element of this pathway is a newly defined rigid, but movable, domain
      that on one side interacts with the alpha-subunit via loop alphaL2 and on the
      other side with the beta-active site. These findings provide a structural basis
      for understanding the allosteric properties of tryptophan synthase.

PMID- 9548922
TI  - Three-dimensional structure of kappa-conotoxin PVIIA, a novel potassium channel
      blocking toxin from cone snails.
AB  - kappa-Conotoxin PVIIA from the venom of Conus purpurascens is the first cone
      snail toxin that was described to block potassium channels. We synthesized
      chemically this toxin and showed that its disulfide bridge pattern is similar to
      those of omega- and delta-conotoxins. kappa-conotoxin competes with radioactive
      alpha-dendrotoxin for binding to rat brain synaptosomes, confirming its capacity
      to bind to potassium channels; however, it behaves as a weak competitor. The
      three-dimensional structure of kappa-conotoxin PVIIA, as elucidated by NMR
      spectroscopy and molecular modeling, comprises two large parallel loops
      stabilized by a triple-stranded antiparallel beta-sheet and three disulfide
      bridges. The overall fold of kappa-conotoxin is similar to that of calcium
      channel-blocking omega-conotoxins but differs from those of potassium channel
      blocking toxins from sea anemones, scorpions, and snakes. Local topographies of
      kappa-conotoxin PVIIA that might account for its capacity to recognize Kv1-type
      potassium channels are discussed.

PMID- 9548923
TI  - Intracellular metabolism of human apolipoprotein(a) in stably transfected Hep G2
      cells.
AB  - Lipoprotein(a) [Lp(a)] consists of LDL and the glycoprotein apolipoprotein(a)
      [apo(a)], which are covalently linked via a single disulfide bridge. The
      formation of Lp(a) occurs extracellularly, but an intracellular assembly in human
      liver cells has also been claimed. The human apo(a) gene locus is highly
      polymorphic due to a variable number of tandemly arranged kringle IV repeats. The
      size of apo(a) isoforms correlates inversely with Lp(a) plasma concentrations,
      which is believed to reflect different synthesis rates. To examine this
      association at the cellular level, we analyzed the subcellular localization and
      fate of apo(a) in stably transfected HepG2 cells. Our results demonstrate that
      apo(a) is synthesized as a precursor with a lower molecular mass which is
      processed into the mature, secreted form. The retention times of the precursor in
      the ER positively correlated with the sizes of apo(a) isoforms. The mature form
      was observed intracellularly at low levels and only in the Golgi apparatus. No
      apo(a) was found to be associated with the plasma membrane. Under temperature
      blocking conditions, we did not detect any apo(a)/apoB-100 complexes within
      cells. This finding was confirmed in HepG2 cells transiently expressing KDEL
      tagged apo(a). The precursor and the mature forms of apo(a) were found in the ER
      and Golgi fractions, respectively, also in human liver tissue. From our data, we
      conclude that in HepG2 cells the apo(a) precursor, dependent on the apo(a)
      isoform, is retained in the ER for a prolonged period of time, possibly due to an
      extensive maturation process of this large protein. The assembly of Lp(a) takes
      place exclusively extracellularly following the separate secretion of apo(a) and
      apoB.

PMID- 9548924
TI  - Dynamics in psoralen-damaged DNA by 1H-detected natural abundance 13C NMR
      spectroscopy.
AB  - The dynamics of the DNA oligomer d(GCGTACGC)2 and the 4'-(hydroxymethyl)-4,5',8
      trimethylpsoralen-DNA furanside monoadduct (MAf) of this oligomer have been
      determined from NMR relaxation parameters. Longitudinal and transverse 13C
      relaxation rates and heteronuclear NOE relaxation data have been measured at
      natural abundance and have been analyzed in the context of the Lipari and Szabo
      model-free formalism. The generalized order parameters for methine carbons in the
      octamer sequence d(GCGTACGC)2 (UM) are relatively and uniformly high for the
      entire molecule. The generalized order parameters for methine carbons in the MAf
      are significantly lower for the deoxyribose bearing the damaged thymidine base
      and for the bases flanking the lesion on the undamaged strand, indicating
      additional conformational flexibility due to the lesion. The order parameters for
      the bases on the damaged strand flanking the lesion remain high. Analysis of the
      relaxation data indicates substantial chemical exchange for the adenosine
      residues in the UM TpA site, and this chemical exchange is quenched upon MAf
      formation. These data are discussed in terms of a model for DNA damage
      recognition by the nucleotide excision repair system.

PMID- 9548925
TI  - Direct force measurements of insulin monomer-monomer interactions.
AB  - Direct measurement of the forces involved in protein-protein and protein-receptor
      interactions can, in principle, provide insight necessary for the advancement of
      structural biology, molecular biology, and the development of therapeutic
      proteins. The protein insulin is illustrative in this respect as the mechanisms
      of insulin dimer dissociation and insulin-insulin receptor binding are crucial to
      the efficacy of insulin medications for the control of diabetes. Insulin
      molecules, modified with a photochemically active azido functionality on specific
      residues, were attached to force microscope tips and opposing mica surfaces in
      configurations that would either favor or disfavor dimer formation. Force curve
      measurements performed in buffer solution revealed the complexity of the insulin
      monomer-monomer interaction with multiple unbinding events occurring upon tip
      retraction, suggesting disruption of discrete molecular bonds at the monomer
      monomer interface. Furthermore, the force curves exhibit long-range unbinding
      events, consistent with considerable elongation of the insulin molecule prior to
      dissociation. The unbinding forces observed in this study are the result of a
      combination of molecular disentanglement and dimer dissociation processes.

PMID- 9548926
TI  - Thermodynamic analysis of calcium and magnesium binding to calmodulin.
AB  - To elucidate some aspects still debated concerning the interaction of Ca2+ and
      Mg2+ with CaM, the thermodynamic binding parameters of Ca2+-CaM and Mg2+-CaM
      complexes were characterized by flow dialysis and isothermal microcalorimetry
      under different experimental conditions. In particular, the enthalpy and entropy
      changes associated with Ca2+ and Mg2+ binding to their sites were determined,
      allowing a better understanding of the mechanism underlying cation-CaM
      interactions. Ca2+-CaM interaction follows an enthalpy-entropy compensation
      relationship, suggesting that CaM explores a subspace of isoenergetical
      conformations which is modified by Ca2+ binding. This Ca2+-induced change in CaM
      dynamics is proposed to play a key role in CaM function, i.e. in its interaction
      with and/or activation of target proteins. Furthermore, data show that Mg2+ does
      not act as a direct competitor for Ca2+ binding on the four main Ca2+ binding
      sites, but rather as an allosteric effector. This implies that the four main Mg2+
      binding sites are distinct from the EF-hand Ca2+ binding sites. Finally, Ca2+ is
      shown to interact with auxiliary binding sites on CaM. These weak affinity sites
      were thermodynamically characterized. The results presented here challenge the
      current accepted view of CaM ion binding.

PMID- 9548927
TI  - Native myosin from adult rabbit skeletal muscle: isoenzymes and states of
      aggregation.
AB  - The globular heads of skeletal muscle myosin have been shown to exist as
      isoenzymes S1 (A1) and S1 (A2), and there are also isoforms of the heavy chains.
      Using capillary electrophoresis, we found two dominant isoenzymes of the whole
      native myosin molecule, in agreement with what has previously been found by
      various techniques for native and nondenatured myosin from adult rabbits.
      Findings about possible states of aggregation of myosin and its heads are
      contradictory. By analytical ultracentrifugation, we confirmed the existence of a
      tail-tail dimer. By laser light scattering, we found a head-head dimer in the
      presence of MgATP. Capillary electrophoresis coupled with analytical
      ultracentrifugation and laser light scattering led us to refine these results. We
      found tail-tail dimers in a conventional buffer. We found tail-tail and head-head
      dimers in the presence of 0.5 mM MgATP and pure head-head dimers in the presence
      of 6 mM MgATP. All the dimers were homodimers. Naming the dominant isoenzymes of
      myosin a and b, we observed tail-tail dimers with isoenzyme a (TaTa) and with
      isoenzyme b (TbTb) and also head-head dimers with isoenzyme a (HaHa) and with
      isoenzyme b (HbHb).

PMID- 9548929
TI  - Roles of conserved arginine residues in the metal-tetracycline/H+ antiporter of
      Escherichia coli.
AB  - Seven arginine residues are conserved in all the tetracycline/H+ antiporters of
      Gram-negative bacteria. Four (Arg67, -70, -71, and -127) of them are located in
      the putative cytoplasmic loop regions and three (Arg31, -101, and -238) in the
      putative periplasmic loop regions [Eckert, B., and Beck, C. F. (1989) J. Biol.
      Chem. 264, 11663-11670]. These arginine residues were replaced by alanine,
      lysine, or cysteine one by one through site-directed mutagenesis. None of the
      mutants showed significant alteration of the protein expression level. The
      mutants resulting in the replacement of Arg31, Arg67, Arg71, and Arg238 with
      either Ala, Cys, or Lys retained tetracycline resistance levels comparable to
      that of the wild type. Among them, only the Arg238 --> Ala mutant showed very low
      transport activity in everted membrane vesicles, probably due to the instability
      of the mutant protein. The replacement of Arg70 and Arg127 with Ala or Cys
      resulted in a drastic decrease in the drug resistance and almost complete loss of
      the transport activity, while the Lys replacement mutants retained significant
      resistance and transport activity, indicating that the positively charged side
      chains at these positions conferred the transport function. On the other hand,
      neither the Ala, Cys, nor Lys replacement mutant of Arg101 exhibited any drug
      resistance or transport activity. As for the reactivity of the Cys replacement
      mutants, only two (Arg71 --> Cys and Arg101 --> Cys) were not reactive with NEM,
      the other five mutants being highly or moderately reactive. The reactivity of the
      cysteine-scanning mutants around Arg101 with NEM revealed that Arg101 is located
      in transmembrane helix IV. It is not likely that Arg101 confers the protein
      folding through a salt bridge with a transmembrane acidic residue because no
      double mutants involving Arg101 --> Ala and the replacement of one of three
      transmembrane acidic residues (Asp15, Asp84, and Asp285) showed the recovery of
      any tetracycline resistance or transport activity. The effect of tetracycline on
      the [14C]NEM binding to the combined mutants S65C/R101A and L97C/R101A suggests
      that Arg101 may cause a substrate-induced conformational change of the putative
      exit gate of TetA(B).

PMID- 9548928
TI  - Utilization of a soluble integrin-alkaline phosphatase chimera to characterize
      integrin alpha 8 beta 1 receptor interactions with tenascin: murine alpha 8 beta
      1 binds to the RGD site in tenascin-C fragments, but not to native tenascin-C.
AB  - The integrin alpha 8 beta 1 has been reported to bind to fibronectin,
      vitronectin, and tenascin-C in cell adhesion or neurite outgrowth assays. Here,
      we describe cDNA cloning of the murine alpha 8 subunit, purification of a
      recombinant soluble heterodimer consisting of the extracellular domains of the
      murine alpha 8 and beta1 subunits, and development of a sensitive binding assay
      using a modified form of this heterodimer fused to alkaline phosphatase (AP). In
      binding assays, the purified alpha 8 beta 1-AP chimera exhibited the same
      divalent ion requirements for activation and binding specificity as cell surface
      alpha 8 beta 1: in the presence of Mn2+ it bound to fibronectin and vitronectin
      in an RGDS-peptide inhibitable manner. Contrary to previous reports, we found no
      evidence that alpha 8 beta 1, expressed on K562 cells or as an AP chimera,
      interacts strongly with native tenascin-C. In binding, adhesion, and spreading
      assays, significant interactions were observed only to short fragments of
      tenascin-C containing the third fibronectin type III repeat which contains an RGD
      sequence. Full length tenascin-C and longer fragments containing this repeat did
      not appear to serve as ligands, implying that the RGD site in native tenascin-C
      is a cryptic binding site for this integrin, exposed by removal of adjacent
      domains. Soluble integrin-AP chimeras should be generally useful for identifying
      and characterizing integrin interactions with ligands.

PMID- 9548930
TI  - Differential regulation of oxidative and osmotic stress induced Syk activation by
      both autophosphorylation and SH2 domains.
AB  - Syk, a nonreceptor protein-tyrosine kinase, is activated by both oxidative and
      osmotic stress and plays different roles in the transduction of stress signals.
      In this study, the regulation of oxidative and osmotic stress induced Syk
      activation was investigated utilizing Syk-negative DT40 cells, expressing various
      Syk mutants. Phosphorylation of Y518Y519 was demonstrated to be required for both
      oxidative and osmotic stress induced Syk activation. Syk activation by these two
      types of stress stimuli was a combination of both autophosphorylation and the
      activities of additional tyrosine kinases. Oxidative stress induced Syk tyrosine
      phosphorylation was almost completely attributed to autophosphorylation, whereas
      other tyrosine kinases were largely responsible for osmotic stress induced Syk
      tyrosine phosphorylation. Moreover, the Src homology 2 (SH2) domains of Syk
      differentially regulated Syk activation. Both mSH2(N) Syk and mSH2(C) Syk, in
      which the phosphotyrosine-dependent binding motif within the SH2 domains
      contained point mutations, showed a significantly higher activity than that
      observed in wild-type Syk, following osmotic stress treatment. In comparison, in
      response to oxidative stress, only mSH2(N) Syk demonstrated a stronger activation
      than wild-type Syk. Therefore, differential activation and regulation of Syk may
      give an insight into the distinctive functions of Syk in oxidative and osmotic
      stress signaling.

PMID- 9548931
TI  - Structure and function of 6,7-dicarboxyheme-substituted myoglobin.
AB  - Myoglobin was reconstituted with 6,7-dicarboxy-1,2,3,4,5, 8-hexamethylheme, a
      compact synthetic heme with the shortest acid side chains, to pursue the
      structural and functional consequences after intensive disruption of the heme
      propionate-apoglobin linkages in the native protein. The electron-withdrawing
      carboxylate groups directly attached to the porphyrin ring lowered the oxygen
      affinity by 3-fold as compared with native myoglobin. Autoxidation of the oxy
      derivative to the ferric protein proceeded with 1.6 x 10(-)2 min-1 at pH 7.0 and
      30 degrees C. The crystallographic structure of the cyanomet myoglobin with 1.9 A
      resolution shows that the heme adopts a unique orientation in the protein pocket
      to extend the two carboxylates toward solvent sphere. The native globin fold is
      conserved, and the conformations of globin side chains are almost intact except
      for those located nearby the heme 6,7-carboxylates. The 7-carboxylate only weakly
      interacts with Ser92 and His97 through two mediating water molecules. The 6
      carboxylate, on the other hand, forms a novel salt bridge with Arg45 owing to
      conformational flexibility of the guanidinium side chain. The proton NMR shows
      that the small heme does not fluctuate about the iron-histidine bond even at 55
      degreesC, suggesting that the salt bridge between Arg45 and heme 6-carboxylate is
      of critical importance to recognize and fix the heme in myoglobin.

PMID- 9548932
TI  - The cyanobacterium Spirulina platensis contains a long wavelength-absorbing
      pigment C738 (F76077K) at room temperature.
AB  - Spirulina platensis is a cyanobacterium which usually lives under high-light
      conditions. Nonetheless, it is thought to contain the most red-shifted antenna
      pigment of all known Chl a-containing phototrophic organisms, as shown by its 77
      K fluorescence peaking at 760 nm. To exclude preparation artifacts and to exclude
      the possibility that long wavelength-absorbing pigments form only when the
      temperature is lowered to 77 K, we carried out experiments with whole cells at
      room temperature. The combined analysis of stationary absorption and fluorescence
      spectra as well as fluorescence induction and time-resolved fluorescence decays
      shows that the pigment responsible for the 77 K fluorescence at 760 nm (i) has
      the oscillator strength of approximately one Chl a molecule, (ii) absorbs
      maximally at 738 nm (), (iii) is present only in the antenna system of PS I, (iv)
      participates in light collection, and (v) does not entail a low photochemical
      quantum yield. Other, more abundant but less red-shifted Chl a antenna pigments
      lead to a significantly larger absorption cross section of the photosynthetic
      unit of PS I above 700 nm compared to units that would not possess these long
      wavelength-absorbing pigments. These results support the hypothesis that the
      physiological role of long wavelength-absorbing pigments is to increase the
      absorption cross section at wavelengths of >700 nm when in densely populated mats
      the spectrally filtered light is relatively more intense at these wavelengths
      [Trissl, H.-W. (1993) Photosynth. Res. 35, 247-263].

PMID- 9548934
TI  - Room-temperature vibrational difference spectrum for S2QB-/S1QB of photosystem II
      determined by time-resolved Fourier transform infrared spectroscopy.
AB  - Time-resolved FTIR spectroscopy has been used to kinetically characterize the
      vibrational properties of intact photosystem II-enriched membrane samples
      undergoing the S1QB-to-S2QB- transition at room temperature. To optimize the
      experimental conditions for the FTIR measurements, oxygen polarographic and
      variable chlorophyll a fluorescence measurements were used to define the decay of
      S2 and QA-, respectively. The flash-induced S2QB-/S1QB difference spectra were
      measured at a temporal resolution of 4.44 s and a spectral resolution of 4 cm-1.
      An intense positive band is observed at 1480 cm-1 in the difference spectrum and
      shows a slow decay with a half time of approximately 13 s. Based on its decay
      kinetics and analogy to the infrared absorption of QA- of photosystem II and QB-
      in bacterial reaction centers, we conclude that the 1480 cm-1 band arises from QB
      of PSII and tentatively assign it to the upsilon(CO) mode of the semiquinone
      anion QB-. The infrared spectral features attributed to the S1-to-S2 transition
      of the Mn cluster at room temperature show striking similarity to the S2/S1
      difference spectrum measured at cryogenic temperatures (Noguchi, T., Ono, T.-A.,
      and Inoue, Y. (1995) Biochim. Biophys. Acta 1228, 189-200).

PMID- 9548933
TI  - Membrane-anchored cytochrome cy mediated microsecond time range electron transfer
      from the cytochrome bc1 complex to the reaction center in Rhodobacter capsulatus.
AB  - In Rhodobacter capsulatus, the soluble cytochrome (cyt) c2 and membrane
      associated cyt cy are the only electron carriers which operate between the
      photochemical reaction center (RC) and the cyt bc1 complex. In this work, cyt cy
      mediated microsecond time range electron transfer kinetics were studied by light
      activated time-resolved absorption spectroscopy using a mutant strain lacking cyt
      c2. In intact cells and in isolated chromatophores of this mutant, only
      approximately 30% of the RCs had their photooxidized primary donor rapidly
      rereduced by cyt cy. Of these 30%, about half were reduced with a half-time of
      approximately 5 micros attributed to preformed complexes, and the other half with
      a half-time of approximately 40 micros attributed to cyt cy having to move from
      another site. This slower phase was affected by addition of glycerol, indicating
      its dependence on the viscosity of the medium. Cyt cy, despite its rereduction by
      ubihydroquinone oxidation in the millisecond time range, remained virtually
      unable to deliver electrons to other RCs which stayed photooxidized for several
      seconds. Furthermore, using two flashes separated by a variable time interval, it
      was shown that the fast electron donating complex was reformed in about 60
      micros, a time span probably reflecting electron transfer from cyt c1 to cyt cy.
      In the absence of the cyt bc1 complex, the steady-state level of cyt cy in the
      chromatophore membranes obtained using cells grown in minimal medium was
      decreased to approximately 50%. The remaining cyt cy , however, was able to form
      the fast electron donating complex with the RC (half-time of approximately 5
      micros), whereas the slower phase with a half-time of approximately 40 micros was
      strongly decelerated. This finding suggests a role for the cyt bc1 complex in
      stabilizing cyt cy and providing its "other" site, possibly via a close
      association between these components. Taken together, it is concluded that
      although cyt cy is present in substoichiometric amount compared to the RCs, it
      supports efficiently photosynthetic growth of R. capsulatus in the absence of cyt
      c2 because it can mediate fast electron transfer from the cyt bc1 complex to the
      RC during multiple turnovers of the cyclic electron flow.

PMID- 9548935
TI  - Spectroscopic comparisons of the pH dependencies of Fe-substituted (Mn)superoxide
      dismutase and Fe-superoxide dismutase.
AB  - We have compared the active sites of Escherichia coli Fe-substituted
      (Mn)superoxide dismutase [Fe-sub-(Mn)SOD] and Fe-SOD to elucidate the basis for
      the inactivity of Fe-sub-(Mn)SOD, despite its apparent similarity to Fe-SOD. The
      active site of (reduced) Fe2+-sub-(Mn)SOD is qualitatively similar to that of
      native Fe2+-SOD, indicating similar active site structures and coordination
      environments for Fe2+. Its nativelike pK is indicative of nativelike local
      electrostatics, and consistent with Fe2+-sub-(Mn)SOD's retention of ability to
      reduce O2*- [Vance and Miller (1998) J. Am. Chem. Soc. 120(3), 461-467]. The
      active site of (oxidized) Fe3+-sub-(Mn)SOD differs from that of Fe3+-SOD with
      respect to the EPR signals produced at both neutral and high pH, indicating
      different coordination environments for Fe3+. Although Fe3+-sub-(Mn)SOD binds the
      small anions N3- and F-, the KD for N3- is tighter than that of Fe3+-SOD,
      suggesting that the (Mn)SOD protein favors anion binding more than does the
      (Fe)SOD protein. The EPR spectral consequences of binding F- are reminiscent of
      those observed upon binding the first F- to Fe3+-SOD, but the EPR spectrum
      obtained upon binding N3- is different, consistent with crystallographic
      observation of a different binding mode for N3- in Thermus thermophilus Mn-SOD
      than Fe-SOD [Lah, M., et al. (1995) Biochemistry 34, 1646-1660]. We find a pK of
      8.5 to be associated with dramatic changes in the EPR spectrum. In addition, we
      confirm the pK between 6 and 7 that has previously been reported based on changes
      in the optical signal and N3- binding [Yamakura, F., et al. (1995) Eur. J.
      Biochem. 227, 700-706]. However, this latter pK appears to be associated with
      much subtler changes in the EPR spectrum. The non-native pKs observed in Fe3+-sub
      (Mn)SOD and the differences in the Fe3+ coordination indicated by the EPR spectra
      are consistent with Fe3+-sub-(Mn)SOD's inability to oxidize O2*- and suggest that
      its low E degrees is due to perturbation of the oxidized state.

PMID- 9548936
TI  - Gemcitabine 5'-triphosphate is a stoichiometric mechanism-based inhibitor of
      Lactobacillus leichmannii ribonucleoside triphosphate reductase: evidence for
      thiyl radical-mediated nucleotide radical formation.
AB  - Ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii
      utilizes adenosylcobalamin and catalyzes the conversion of nucleoside
      triphosphates to deoxynucleoside triphosphates. One equivalent of 2',2'-difluoro
      2'-deoxycytidine 5'-triphosphate, F2dCTP, rapidly inactivates RTPR. Analysis of
      the reaction products reveals that inactivation is accompanied by release of two
      fluoride ions and 0.84 equiv of 5'-deoxyadenosine and attachment of 1 equiv of
      corrin covalently to an active-site cysteine residue of RTPR. No cytosine release
      was detected. Proteolysis of corrin-labeled RTPR with endoproteinase Glu-C and
      peptide mapping at pH 5.8 revealed that C419 was predominantly modified. The
      kinetics of the inactivation have been examined by stopped-flow (SF) UV-vis
      spectroscopy and rapid freeze quench (RFQ) electron paramagnetic resonance (EPR)
      spectroscopy. Monitoring DeltaA525 nm shows that cob(II)alamin is formed with an
      apparent kobs of 50 s-1, only 2. 5-fold slower than a similar experiment carried
      out with cytidine 5'-triphosphate (CTP). The same reaction mixture was thus
      quenched at times from 22 ms to 30 s and examined by EPR spectroscopy. At early
      time points the EPR spectrum resembled a thiyl radical exchange coupled to
      cob(II)alamin. From 22 to 255 ms the total spin concentration remained unchanged
      at 1.4 spins/RTPR, twice that predicted by the amount of cob(II)alamin determined
      by SF. However, with time the signal attributed to the thiyl radical
      cob(II)alamin disappears and new signal(s) with broad feature(s) at g = 2.33 and
      a sharp feature at g = 2.00 appeared, suggesting formation of cob(II)alamin and a
      nucleotide-based radical with only dipolar interactions. These studies have been
      interpreted to support the proposal that an RTPR-based thiyl radical can give
      rise to a nucleotide-based radical.

PMID- 9548937
TI  - Effect of DNA secondary structure on human telomerase activity.
AB  - Telomeres are specialized DNA-protein complexes located at the chromosome ends.
      The guanine-rich telomeric sequences have the ability to form G-quadruplex
      structures under physiological ionic conditions in vitro. Human telomeres are
      maintained through addition of TTAGGG repeats by the enzyme telomerase. To
      determine a correlation between DNA secondary structure and human telomerase,
      telomerase activity in the presence of various metal cations was monitored.
      Telomerase synthesized a larger proportion of products corresponding to four,
      five, eight, and nine full repeats of TTAGGG in 100 mM K+ and to a lesser extent
      in 100 mM Na+ when a d(TTAGGG)3 input primer was used. A more even product
      distribution was observed when the reaction mixture contained no added Na+ or K+.
      Increasing concentrations of Cs+ resulted in a loss of processivity but not in
      the distinct manner observed in K+. When the input primer contained 7-deaza-dG,
      the product distribution resembled that of reactions without K+ even in the
      presence of 100 mM K+. Native polyacrylamide gel electrophoresis indicated that
      d(TTAGGG)4, d(TTAGGG)5, d(TTAGGG)8, and d(TTAGGG)9 formed compact structures in
      the presence of K+. The oligonucleotide d(TTAGGG)4 had a UV spectrum
      characteristic of that of the G-quadruplex only in the presence of K+ and Na+. A
      reasonable explanation for these results is that four, five, eight, and nine
      repeats of TTAGGG form DNA secondary structures which promote dissociation of the
      primer from telomerase. This suggests that telomerase activity in cells can be
      modulated by the secondary structure of the DNA template. These findings are of
      probable relevance to the concept of telomerase as a therapeutic target for drug
      design.

PMID- 9548938
TI  - Location of subunit-subunit contact sites on RNA polymerase II subunit 3 from the
      fission yeast Schizosaccharomyces pombe.
AB  - RNA polymerase II from the fission yeast Schizosaccharomyces pombe consists of 10
      putative subunits. Subunit 3 (Rpb3) is a homologue of prokaryotic alpha subunit,
      which plays a key role in the assembly of core enzyme subunits. Previously we
      indicated that Rpb3 also plays an essential role in subunit assembly because it
      interacts with at least four subunits, two large subunits (Rpb1 and Rpb2) and two
      medium-sized subunits (Rpb3 and Rpb5) (1), and it constitutes a core subassembly
      consisting of Rpb2, Rpb3, and Rpb11 (2). Using a synthetic mixture of equimolar
      amounts of individual subunits, which were all purified from cDNA-expressed
      Escherichia coli, we found here that Rpb3 also interacts with Rpb11, another
      alpha homologue. By making a set of Rpb3 deletion derivatives, we carried out
      mapping of the Rpb5- and Rpb11-contact sites on Rpb3. By far-Western blot and GST
      pull-down assays, we found that the amino acid sequence between residues 105-263
      of Rpb3 is involved in binding Rpb5, and the sequence between residues 105-297 is
      required for binding Rpb11. Although the Rpb5- and Rpb11-contact sites on Rpb3
      overlap each other, both subunits are able to associate with Rpb3 simultaneously.
      The binding of Rpb5 stabilizes the Rpb3-Rpb11 heterodimer.

PMID- 9548939
TI  - Binding of neomycin to the TAR element of HIV-1 RNA induces dissociation of Tat
      protein by an allosteric mechanism.
AB  - Neomycin inhibits the binding of Tat-derived peptides to the trans-activating
      region (TAR) of HIV-1 RNA. Kinetic studies reveal that neomycin acts as a
      noncompetitive inhibitor that can bind to the Tat-TAR complex and increase the
      rate constant (koff) for dissociation of the peptide from the RNA. Neomycin
      effects a conformational change in the structure of TAR that can be detected by
      circular dichroism spectroscopy. The increase in ellipticity measured at 265 nm
      upon binding of the aminoglycoside is opposite to the decrease seen when Tat
      peptides bind to the RNA. Thus, the structural transition induced by neomycin is
      apparently incompatible with the binding of Tat and underlies the inhibitory
      action of the antibiotic. The binding site for neomycin on TAR was identified in
      ribonuclease protection experiments and is located in the stem immediately below
      the three-nucleotide bulge that serves as the primary identity element for Tat.
      Apparent protection of residues in the bulge by neomycin may represent additional
      contacts to the aminoglycoside, but more likely result from changes in the
      structure of this region when the ligand binds to the RNA. Binding assays using
      variants of TAR in which inosine residues were substituted for guanosine residues
      support the results from the ribonuclease protection experiments. Inosine
      substitutions in the lower stem, but not the upper stem, decrease the binding
      constant for neomycin by approximately 100-fold. Neither of these variants
      affected the binding affinity of Tat peptide. In addition, these latter
      experiments suggest that the aminoglycoside may be located in the minor groove of
      the stem. This mode of association may be a critical aspect of neomycin's ability
      to bind to the Tat-TAR complex and could serve as a guide for the design of other
      drugs that bind to specific RNA targets as noncompetitive inhibitors.

PMID- 9548940
TI  - Cross-talk between protein kinase C-alpha (PKC-alpha) and -delta (PKC-delta): PKC
      alpha elevates the PKC-delta protein level, altering its mRNA transcription and
      degradation.
AB  - Studies utilizing the overexpression of individual isoforms indicated that both
      PKC-alpha and -delta promote a number of biological effects, including inhibition
      of DNA synthesis associated with rearrangements of the actin cytoskeleton in the
      murine B-cell lymphoma (Baf3), differentiation of the murine promyelocyte line
      32D, and activation of MAP kinase in CHO fibroblasts. We postulated that these
      results reflect some form of cross-regulation between PKC-alpha and -delta rather
      than their functional redundancy. In this report, we show that overexpression of
      PKC-alpha in Baf3 and 32D leads to an elevation of the endogenous PKC-delta mRNA
      and protein levels. The elevated steady-state PKC-delta mRNA level results from a
      combination of increased PKC-delta transcription and mRNA stability. Upregulation
      of PKC-delta mRNA by PKC-alpha occurs even after a selective depletion of the PKC
      delta protein. In addition, phorbol ester-induced elevation of PKC-delta mRNA and
      protein levels can be prevented by the PKC inhibitor GF109203X, an indication of
      the requirement for PKC kinase activity. Inhibition of new protein synthesis by
      cycloheximide showed that upregulation of PKC-delta mRNA, as opposed to delayed
      downregulation of the PKC-delta protein, is primarily responsible for the
      accumulation of this isoform by PKC-alpha. In parental Baf3 and 32D cells and PKC
      alpha overexpressers, PKC-alpha and PKC-delta are uniquely involved in cross
      regulation, while PKC-epsilon, PKC-eta, and PKC-mu are not.

PMID- 9548941
TI  - Role of phosphorylation in determining the backbone dynamics of the
      serine/threonine-proline motif and Pin1 substrate recognition.
AB  - Proline residues provide a backbone switch in a polypeptide chain, which is
      controlled by the cis/trans isomerization about the peptidyl-prolyl bond.
      Phosphorylation of serine- and threonine-proline motifs has been shown to be a
      critical regulatory event for many proteins. The biological significance of these
      motifs has been further highlighted by the discovery of a novel and essential
      peptidyl-prolyl cis/trans isomerase Pin1. Pin1 is required for progression
      through mitosis via catalyzing the isomerization of phosphorylated Ser/Thr-Pro
      motifs specifically present in mitosis-specific phosphoproteins. However, little
      is known whether the phosphorylation regulates the conformational switch of the
      Ser/Thr-Pro bonds. Here, we report the synthesis and conformational
      characterization of a series of peptides that contain the phosphorylated or
      nonphosphorylated Ser/Thr-Pro motifs. Phosphorylation affected the rate of the
      cis to trans isomerization of the Thr/Ser-Pro bonds. As determined by a protease
      coupled assay, the isomerization rate of phosphorylated Thr-Pro bond was found to
      be 8-fold slower than that of the nonphosphorylated analogue. Furthermore,
      studies of the pH dependence of the isomerization of the phosphopeptides reveal
      that both cis content and the rate constant of prolyl cis to trans isomerization
      are lower for the dianionic state of the phosphothreonine-containing peptides.
      These effects of phosphorylation are specific for phosphorylated Ser/Thr since
      neither phosphorylated Tyr nor glutamic acid was able to affect the prolyl
      isomerization. Finally, our experiments provide evidence that effective catalysis
      of cis/trans isomerization of phosphorylated Ser/Thr-Pro bonds by Pin1 is
      specific to the dianionic form of the substrate. Thus, our results demonstrate
      that protein phosphorylation specifically regulates the backbone dynamics of the
      Ser/Thr-Pro motifs and that Pin1 specifically isomerizes the certain conformation
      of the phosphorylated Ser/Thr-Pro motifs.

PMID- 9548942
TI  - Investigation of the cooperative structure of Fc fragments from myeloma
      immunoglobulin G.
AB  - The cooperative structure of Fc fragments prepared from myeloma human IgG1 was
      studied using scanning microcalorimetry and fluorescence at pH 4.2-8.0. It was
      shown that the first to be melted are CH2 domains whose interaction with each
      other is rather weak, while that with CH3 domains is strong. Then CH3 domains
      which form a single cooperative block are melted. The data for the structure of
      the Fc fragment in solution agree with the X-ray data according to which the
      interaction between CH2 domains is mediated by the carbohydrate moiety while the
      two CH3 domains are strongly associated. The presence of intensive CH2-CH3
      interaction is a distinctive feature of the state of the Fc fragment in the given
      pH region as compared to that at pH <4.1 [Tischenko, V. M., et al. (1982) Eur. J.
      Biochem. 126, 517-521; Ryazantsev, S., et al. (1990) Eur. J. Biochem. 190, 393
      399]. First, cis interactions greatly increase the free energy of the native
      structure stabilization in CH2 domains. Second, they decrease this energy for CH3
      domains when compared to the state of the latter at pH 3.8 or within the Fc'
      fragment (the dimer of CH3 domains). The temperature and enthalpy of melting of
      CH2 domains coincide in all the samples studied despite heterogeneity of the
      carbohydrate moiety. Thus, it may be postulated that the conservative part of CH2
      domains makes a cardinal contribution to the interaction of these domains with
      the carbohydrate moiety.

PMID- 9548943
TI  - Interaction of a type II myosin with biological membranes studied by 2H solid
      state NMR.
AB  - Deuterium nuclear magnetic resonance spectroscopy (2H NMR) has been employed to
      investigate the interaction of lung type II myosin protein with neutral bilayers
      containing dimyristoylphosphatidylcholine (DMPC) as the only constituent and
      mixed bilayers containing the negatively charged lipid
      dimyristoylphosphatidylglycerol (DMPG). DMPC was deuterated at its headgroup by
      substituting the four protons at the alpha- and beta-positions (DMPC-d4) and the
      nine protons at the gamma-position (DMPC-d9). DMPG was perdeuterated at its
      headgroup (DMPG-d5). No changes were observed in the quadrupole splittings or
      spin-lattice relaxation times for the deuterated DMPC headgroup segments when
      increasing amounts of myosin were added to liposomes, made exclusively of DMPC-d9
      or of DMPC-d4. However, upon the insertion of the negatively charged lipid DMPG
      at 1:1 molar ratio into the DMPC bilayers, myosin was found to interact
      electrostatically with the liposomes, thereby affecting significantly both the
      quadrupole splittings and spin-lattice relaxation rates of the alpha-, beta-, and
      gamma-deuterons in labeled DMPC. Monitoring DMPG-d5 in mixed DMPC/DMPG bilayers
      revealed a direct electrostatic interaction of DMPG with the protein, where
      positively charged lysine residues located at the tail domain of myosin provide
      the necessary sites for the interaction to occur. When ATP and Mg2+ were
      complexed to the head domain of myosin, a reduced interaction with the negatively
      charged bilayers was observed. The results clearly indicate that a type II myosin
      can interact with membranes without the need for a specific hydrophobic domain or
      an anchor in the protein molecule, provided that negatively charged lipids are
      present in the bilayer.

PMID- 9548944
TI  - Time-resolved circular dichroism studies of protein folding intermediates of
      cytochrome c.
AB  - The circular dichroism spectra of cytochrome c (cytc) in 4.6 M guanidine
      hydrochloride (pH 6.5) indicate that the secondary structure in reduced cytc is
      near-native, whereas in the CO-bound species (COCytc) it is substantially
      unfolded. Photolysis of COCytc should thus induce large changes in the secondary
      structure, which can be probed with time-resolved circular dichroism (TRCD)
      spectroscopy in the far-UV region. Time-resolved absorption (TROA) and TRCD
      methods were used to study the photolysis reaction of COCytc in efforts to
      identify structural intermediates in cytc folding on time scales from nanoseconds
      to seconds. TROA data from the Soret region, similar to previous studies, showed
      four intermediates with lifetimes of 2, 50, 225, and 880 micros. The 2-micros
      process is proposed to involve Fe(II)-Met80 coordination. Approximately 7% of the
      native CD signal was observed in the TRCD signal at 220 nm within 500 ns, with no
      significant additional secondary structure formation observed. Further folding
      after 2 micros may be inhibited by ligation of His26/His33 with Fe(II), which is
      suggested to be associated with the 50-micros phase. The two slowest components,
      tau = 225 and 880 micros, are attributed to CO rebinding on the basis of mixed
      gas experiments. CO rebinding is expected to compete with protein folding and
      favor the unfolded state. However, when the two CO rebinding lifetimes are
      extended into milliseconds by reducing the CO concentration, there is still no
      significant increase in CD signal at 220 nm.

PMID- 9548945
TI  - Internal motion of lysozyme studied by time-resolved fluorescence depolarization
      of tryptophan residues.
AB  - The internal motion of lysozyme was described by the steady-state and time
      resolved fluorescence anisotropy of its tryptophan residues. The fluorescence of
      mutant lysozymes W62Y- and W108Y-lysozyme, in which Trp62 or Trp108 of hen egg
      white lysozyme was replaced with a tyrosine residue, could be respectively
      assigned to Trp108 or Trp62 at the longer wavelength region of the total
      fluorescence spectrum. The segmental motion of Trp62 as shown by its fluorescence
      anisotropy decay was described with two components originating from the
      fluctuational rotation of an indole moiety about the Calpha-Cbeta bond and
      rotational wobble of the peptide segment adjacent to Trp62. Although Trp62 showed
      a high degree of motional freedom, its motion was significantly suppressed by the
      interaction of the mutant protein with a trimer of N-acetyl-D-glucosamine. By
      contrast, the segmental motion of Trp108 is hindered by the local cage structure
      at temperatures below 30 degreesC, but Relief from restricted motion occurred on
      the formation of ligand complex or by thermal agitation. Because of overlaps of
      the fluorescence spectrum, it is difficult to assign the segmental motion of
      Trp28 or Trp111, the other two tryptophan residues in lysozyme. However, a
      careful analysis of the fluorescence anisotropy decay of W62Y- and W108Y-lysozyme
      showed that the fluctuation of the hydrophobic matrix box was greater than that
      expected from lysozyme's crystal structure, although it was suppressed by the
      binding of the ligand to the active site of lysozyme.

PMID- 9548946
TI  - The apolar distal histidine mutant (His69-->Val) of the homodimeric Scapharca
      hemoglobin is in an R-like conformation.
AB  - The effect of the apolar mutation of the distal histidine (His69-->Val) has been
      studied in the cooperative homodimeric hemoglobin from the mollusc Scapharca
      inaequivalvis. Absorption, circular dichroism, and resonance Raman spectroscopy
      point to a more symmetric heme structure of the deoxy derivative, which is
      indicative of an R-like conformation of the deoxy heme. Resonance Raman
      spectroscopy also brings out alterations in the geometry and interactions of the
      bound CO molecule. The iron-carbon stretching frequency is decreased by about 30
      cm-1 with respect to the native protein, while the diatomic ligand stretching
      frequency is increased by about the same degree. Consistent with the structural
      changes, the ligand binding properties are significantly altered. In the mutant
      the overall rate and the affinity for CO binding are increased about 100-fold
      with respect to the native protein, and cooperativity is abolished. In addition,
      the amplitude and the rate of the geminate rebinding process increase
      significantly. This finding may be correlated to the longer average residence
      time of the photolyzed CO molecule within the heme pocket of the H69V mutant, as
      indicated by molecular dynamics simulations.

PMID- 9548947
TI  - Backbone cyclic peptide, which mimics the nuclear localization signal of human
      immunodeficiency virus type 1 matrix protein, inhibits nuclear import and virus
      production in nondividing cells.
AB  - Here, we describe an application of the backbone cyclic (BC) proteinomimetic
      approach to the design and the synthesis of a BC peptide which functionally
      mimics the nuclear localization signal (NLS) region of the human immunodeficiency
      virus type 1 matrix protein (HIV-1 MA). On the basis of the NMR structure of HIV
      1 MA, a library of BC peptides was designed and screened for the ability to
      inhibit nuclear import of NLS-BSA in digitonin-permeabilized HeLa and Colo-205
      cultured cells. The screening yielded a lead compound (IC50 = 3 microM) which was
      used for the design of a second library. This library led to the discovery of a
      highly potent BC peptide, designated BCvir, with an IC50 value of 35 nM. This
      inhibitory potency is compared to a value of 12 microM exhibited by the linear
      parent HIV-1 MA NLS peptide. BCvir also reduced HIV-1 production by 75% in
      infected nondividing cultured human T-cells and was relatively resistant to
      tryptic digestion. These properties make BCvir a potential candidate for the
      development of a novel class of antiviral drugs which will be based on blocking
      nuclear import of viral genomes.

PMID- 9548948
TI  - Synergistic effects of diacylglycerols and fatty acids on membrane structure and
      protein kinase C activity.
AB  - The synergistic effects of diacylglycerol (DAG) and fatty acid (FA) in activating
      protein kinase C have been investigated by correlating their individual and
      combined effects on enzymatic activity and on membrane structure in
      phosphatidylcholine/phosphatidylserine (4:1) lipid mixtures using a combination
      of specific enzymatic assays and 31P and 2H NMR. Addition of DAGs and unsaturated
      FAs to the bilayers synergistically increased the tendency of the lipids to form
      nonbilayer phases with a concomitant increase in PKC activity until a maximum was
      achieved. Further increases in the DAG/FA concentration led to the formation of
      the nonbilayer lipid phases under the conditions of the PKC activity assays and
      correlated with decreased activity. The nonbilayer lipid phases still supported
      PKC activity, although with less than 50% efficiency as compared with the bilayer
      lipids. Long-chain saturated FA increased DAG-induced PKC activity by causing a
      lateral phase separation of gel (Lbeta) and liquid-crystalline (Lalpha) domains.
      Due to the preferential partitioning of DAGs into liquid-crystalline domains, the
      local DAG concentration increased in these domains, leading to an increase in PKC
      activity. Because a wide range of lipophilic compounds is capable of altering
      curvature stress, and therefore the tendency for nonbilayer phase formation in
      cellular membranes, these compounds would be expected to modulate PKC activity
      and the activities of a number of other membrane-associated enzymes that are
      sensitive to biophysical properties of lipid membranes.

PMID- 9548949
TI  - Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen
      peroxide: evidence for a sulfenic acid intermediate and implications for redox
      regulation.
AB  - Protein tyrosine phosphatases (PTPs) catalyze the hydrolysis of phosphotyrosine
      from specific signal-transducing proteins. Although regulatory mechanisms for
      protein kinases have been described, no general mechanism for controlling PTPs
      has been demonstrated. Numerous reports have shown that cellular redox status
      plays an important role in tyrosine phosphorylation-dependent signal transduction
      pathways. This study explores the proposal that PTPs may be regulated by
      reversible reduction/oxidation involving cellular oxidants such as hydrogen
      peroxide (H2O2). Recent reports indicated that H2O2 is transiently generated
      during growth factor stimulation and that H2O2 production is concomitant with
      relevant tyrosine phosphorylation. By use of recombinant enzymes, the effects of
      H2O2 on three PTPs [PTP1, LAR (leukocyte antigen-related), and VHR (vaccinia H1
      related)] and three distinct serine/threonine protein phosphatases (PPs:
      PP2Calpha, calcineurin, and lambda phosphatase) were determined. Hydrogen
      peroxide had no apparent effect on PP activity. In contrast, PTPs were rapidly
      inactivated (kinact = 10-20 M-1 s-1) with low micromolar concentrations of H2O2
      but not with large alkyl hydroperoxides. PTP inactivation was fully reversible
      with glutathione and other thiols. Because of the slower rate of reduction,
      modification occurred even in the presence of physiological thiol concentrations.
      By utilization of a variety of biochemical techniques including chemical
      modification, pH kinetic studies, and mutagenesis, the catalytic cysteine
      thiolate of PTPs was determined to be the selective target of oxidation by H2O2.
      By use of the electrophilic reagent 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD
      Cl), it was shown that a cysteine sulfenic acid intermediate (Cys-SOH) is formed
      after attack of the catalytic thiolate on H2O2. A chemical mechanism for
      reversible inactivation involving a cysteine sulfenic acid intermediate is
      proposed.

PMID- 9548950
TI  - Conformational changes in the extrinsic manganese stabilizing protein can occur
      upon binding to the photosystem II reaction center: an isotope editing and FT-IR
      study.
AB  - Photosystem II catalyzes the light-driven oxidation of water and reduction of
      plastoquinone in oxygenic photosynthesis. The manganese stabilizing protein (MSP)
      of photosystem II is an extrinsic subunit that plays an important role in
      catalytic activity. This subunit can be extracted and re-bound to the photosystem
      II reaction center. Extraction is associated with decreased stability of
      manganese binding by the enzyme and by loss in high rates of oxygen evolution
      activity; reconstitution reverses these phenomena. Since little is known about
      the assembly of complex membrane proteins, we have employed isotope editing and
      vibrational spectroscopy to obtain information about any changes in secondary
      structure that occur in MSP upon functional reconstitution to photosystem II. The
      spectroscopic data obtained are consistent with substantial changes in
      conformation when MSP binds to photosystem II; approximately 30-40% of the
      peptide backbone undergoes a change in secondary structure. These conclusions
      were reached by comparing different aliquots, before and after binding, of the
      same 13[C]MSP sample. Analysis of amide I band line shapes through Fourier
      deconvolution and nonlinear regression suggests that binding of MSP to
      photosystem II is associated with a decrease in random structure and an increase
      in beta-sheet content. We conclude that binding of MSP to the reaction center can
      induce folding of MSP. Our results also indicate that, in solution, MSP can
      sample a variety of conformational states, which differ in hydrogen bonding of
      the peptide backbone.

PMID- 9548951
TI  - Amide modes of the alpha-helix: Raman spectroscopy of filamentous virus fd
      containing peptide 13C and 2H labels in coat protein subunits.
AB  - The filamentous virus fd consists of a single-stranded DNA genome sheathed by
      2700 copies of a 50-residue alpha-helical subunit (protein pVIII) and serves as a
      model assembly of alpha-helices. To advance vibrational assignments for the alpha
      helix, we have investigated Raman spectra of fd virions containing 13C and 2H
      (deuterium) labels at various main-chain sites of the pVIII subunits. 13C was
      introduced at specific peptide carbonyls, while deuterium was introduced at
      selected alpha-carbon (Calpha) and amide nitrogen positions. Interpretation of
      the Raman spectra reveals a previously unrecognized alpha-helix band in the
      spectral interval 730-745 cm-1, tentatively assigned to a carbonyl in-plane
      bending mode (amide IV). Experimental evidence has also been obtained for a
      distinctive alpha-helix marker near 1345 cm-1, assigned to a coupled Calpha-H
      bending and Calpha-C stretching mode. The fd virions containing 13C-labeled
      carbonyls exhibit unexpectedly complex amide I profiles, consisting of multiple
      band components. Amide I splitting resulting from 13C substitution of carbonyls
      is attributed to decoupling of transition-dipole interactions normally occurring
      in the extended pVIII helix. The present study identifies novel conformation
      dependent Raman bands in a native alpha-helix assembly, confirms amide I and
      amide III assignments proposed previously for filamentous viruses, and
      facilitates new Raman assignments for the packaged ssDNA. The alpha-helix markers
      identified here should also be useful in conformation analyses of other proteins
      by Raman spectroscopy.

PMID- 9548952
TI  - Kinetic studies of sequence-specific binding of GCN4-bZIP peptides to DNA strands
      immobilized on a 27-MHz quartz-crystal microbalance.
AB  - Specific protein-DNA interaction was studied quantitatively by using a highly
      sensitive 27-MHz quartz-crystal microbalance (QCM). Biotinylated DNA double
      strands (21 bp, having a CRE site of 5'ATGACGTCAT3') were immobilized on an
      avidin-bound QCM surface, and sequence-specific binding of bZIP 56-mer peptides
      (having both the basic region for binding and the leucine zipper region for
      dimerization) to the DNA strand on the QCM was observed. The binding amount
      (Deltam) at the nanogram level and kinetic parameters such as association
      constants (Ka) and binding and dissociation rate constants (k1 and k-1) could be
      obtained from time courses of QCM frequency decreases. A bZIP peptide as a dimer
      was observed to bind sequence-specifically to one DNA strand having a CRE site.
      Ka values of ss-bZIP, in which the leucine-zipper region of bZIP was substituted
      by a Cys-Cys linkage, were largely decreased, and the sequence selectivity also
      disappeared. Ka values obtained by the QCM method showed good agreement with
      those obtained from the conventional gel mobility shift assay or from circular
      dichroism spectrum changes. When the specific sequence of the CRE site of DNA
      strands was partly changed, Ka values decreased by about a half due to the
      increase of the dissociation rate constant (k-1) independent of the binding rate
      constant (k1).

PMID- 9548953
TI  - The uvsY recombination protein of bacteriophage T4 forms hexamers in the presence
      and absence of single-stranded DNA.
AB  - A prerequisite to genetic recombination in the T4 bacteriophage is the formation
      of the presynaptic filament-a helical nucleoprotein filament containing
      stoichiometric amounts of the uvsX recombinase in complex with single-stranded
      DNA (ssDNA). Once formed, the filament is competent to catalyze homologous
      pairing and DNA strand exchange reactions. An important component in the
      formation of the presynaptic filament is the uvsY protein, which is required for
      optimal uvsX-ssDNA assembly in vitro, and essential for phage recombination in
      vivo. uvsY enhances uvsX activities by promoting filament formation and
      stabilizing filaments under conditions of low uvsX, high salt, and/or high gp32
      (ssDNA-binding protein) concentrations. The molecular properties of uvsY include
      noncooperative binding to ssDNA and specific protein-protein interactions with
      both uvsX and gp32. Evidence suggests that all of these hetero-associations of
      the uvsY protein are important for presynaptic filament formation. However, there
      is currently no structural information available on the uvsY protein itself. In
      this study, we present the first characterization of the self-association of
      uvsY. Using hydrodynamic methods, we demonstrate that uvsY associates into a
      stable hexamer (s020,w = 6.0, M = 95 kDa) in solution and that this structure is
      competent to bind ssDNA. We further demonstrate that uvsY hexamers are capable of
      reversible association into higher aggregates in a manner dependent on both salt
      and protein concentration. The implications for presynaptic filament formation
      are discussed.

PMID- 9548955
TI  - Role of the [4Fe-4S] cluster in reductive activation of the cobalt center of the
      corrinoid iron-sulfur protein from Clostridium thermoaceticum during acetate
      biosynthesis.
AB  - The corrinoid iron-sulfur protein (CFeSP) from Clostridium thermoaceticum
      functions as a methyl carrier in the Wood-Ljungdahl pathway of acetyl-CoA
      synthesis. The small subunit (33 kDa) contains cobalt in a corrinoid cofactor,
      and the large subunit (55 kDa) contains a [4Fe-4S] cluster. The cobalt center is
      methylated by methyltetrahydrofolate (CH3-H4folate) to form a methylcobalt
      intermediate and, subsequently, is demethylated by carbon monoxide
      dehydrogenase/acetyl-CoA synthase (CODH/ACS). The work described here
      demonstrates that the [4Fe-4S] cluster is required to facilitate the reactivation
      of oxidatively inactivated Cob(II)amide to the active Co(I) state. Site-directed
      mutagenesis of the large subunit gene was used to change residue 20 from cysteine
      to alanine, which resulted in formation of a cluster with EPR and redox
      properties consistent with those of [3Fe-4S] clusters. The midpoint potential of
      the cluster in the C20A variant was approximately 500 mV more positive than that
      of the [4Fe-4S] cluster in the native enzyme. Accordingly, it was found that the
      Co center in the C20A mutant protein could be reduced artificially but was
      severely crippled in its ability to be reduced by physiological electron donors.
      This is probably because the reduced cluster of the C20A protein cannot provide
      the driving force needed to reduce Co(II) to Co(I), since the Co(II/I) midpoint
      potential is -504 mV. The C20A variant also was unable to catalyze the steady
      state synthesis of acetyl-CoA when CH3-H4folate or methyl iodide were provided as
      methyl donors and CO and CODH/ACS as reductants. Addition of chemical reductants
      rescued the catalytically crippled variant form in both of these reactions. On
      the other hand, in single-turnover reactions, the methyl-Co state of the altered
      protein was fully active in methylating H4folate and in synthesizing acetyl-CoA
      in the presence of CO and CoA. The combined results strongly indicate that the
      FeS cluster of the CFeSP is necessary for reductive activation of Co(II) to Co(I)
      by physiological reductants but is not required for catalysis, e.g.,
      demethylation of CH3-H4folate or methylation of CODH/ACS. We propose that, during
      reductive activation, electrons flow from the reduced electron-transfer protein
      (e.g., CODH/ACS or reduced ferredoxin (Fd)) to the FeS cluster which then directs
      electrons to the cobalt center for catalysis. These results also support earlier
      hypotheses that the methylation and demethylation reactions involving the CFeSP
      are SN2-type nucleophilic displacement reactions and do not involve radical
      chemistry.

PMID- 9548954
TI  - Intra- vs intersubunit communication in the homodimeric restriction enzyme EcoRV:
      Thr 37 and Lys 38 involved in indirect readout are only important for the
      catalytic activity of their own subunit.
AB  - EcoRV is a dimer of two identical subunits which together form one binding site
      for the double-stranded DNA substrate. Concerted cleavage of both strands of the
      duplex requires intersubunit communication to synchronize the two catalytic
      centers of EcoRV. Here we address the question of how contacts to the DNA
      backbone trigger conformational changes which lead to the activation of both
      catalytic centers. The structure of the specific EcoRV-DNA complex shows that a
      region including amino acids Thr 37 and Lys 38 is involved in interactions with
      the DNA backbone and is a candidate for intersubunit communication. Homodimeric
      EcoRV T37A and K38A variants have a 1000-fold reduced catalytic activity. To
      examine whether Thr 37 and Lys 38 of one subunit affect the catalytic center in
      the same subunit and/or in the other subunit, we have produced heterodimeric
      variants containing a Thr 37 --> Ala or Lys 38 --> Ala substitution in one
      subunit combined with a wild type (wt) subunit (wt/T37A and wt/K38A) or with a
      subunit which contains an amino acid substitution (Asp 90 --> Ala) in the active
      site (D90A/T37A and D90A/K38A). Cleavage experiments with supercoiled pAT153 show
      that wt/T37A and wt/K38A preferentially nick the DNA. A steady-state kinetic
      analysis of the cleavage of an oligodeoxynucleotide substrate shows that the
      activity of wt/T37A and wt/K38A is half of that of wild type EcoRV, whereas
      D90A/T37A and D90A/K38A are almost inactive. These results demonstrate that Thr
      37 and Lys 38 affect primarily the catalytic center in their own subunit and that
      both subunits of EcoRV can be activated independently of each other. We suggest
      that Thr 37 and Lys 38 control the catalytic activity of the active site in their
      own subunit by positioning alpha-helix B.

PMID- 9548956
TI  - Self-association of disulfide-dimerized melittin analogues.
AB  - Two cysteine substitutions of bee venom melittin have been synthesized to
      investigate the effects of disulfide cross-linking on the self-association
      properties of the peptide in solution. K23C melittin (mltK23C) was designed to
      link nonpolar surfaces of the amphipathic melittin helix on the basis of the
      close juxtaposition of pairs of K23 side chains in the crystal of the native
      melittin tetramer. K23Q/Q25C melittin (mltQ25C) was designed to link the polar
      surfaces of the peptide such that self-association in membrane bound states might
      be stabilized. The mltK23C disulfide dimer, (mltK23C)2, is highly structured at
      low pH under conditions where native melittin, and the mltK23C monomer, are
      unstructured. High-resolution NMR, circular dichroism, and fluorescence
      spectroscopy established that (mltK23C)2 is a helical monomer (pseudodimer) with
      stable helical segments between residues 2-13 and 15-25. Although the symmetrical
      nature of the pseudodimer prevented high-resolution structure determination,
      analysis of calculated hydrogen bond lengths, chemical shifts, near-UV circular
      dichroism, and urea denaturation demonstrated similarities with alpha-helical
      coiled coils and with the structure of native melittin in methanol. Stopped flow
      fluorescence showed that (mltK23C)2 underwent pH- and divalent anion-linked
      dimerization to a melittin-like pseudotetramer, indicating that a pair of
      disulfide bonds could be accommodated in a structure similar to the native
      melittin crystal structure. Despite incorporation of two disulfide bonds into the
      melittin tetramer, the folding free energy (DeltaGw) of [(mltK23C)2]2 was similar
      to that for the native melittin tetramer under the condition used. Incorporation
      of a disulfide bond on the polar helix face in melittin did not stabilize helical
      structure in the absence of self-association. Instead, this molecule underwent pH
      and divalent anion-linked self-association to an ill-defined aggregate which
      precipitated.

PMID- 9548957
TI  - Structural transitions accompanying the activation of peptide binding to the
      endoplasmic reticulum Hsp90 chaperone GRP94.
AB  - GRP94, the endoplasmic reticulum Hsp90 paralog, binds a diverse array of
      peptides, a subset of which are suitable for assembly onto nascent MHC class I
      molecules. At present, the mechanism, site, and regulation of peptide binding to
      GRP94 are unknown. Using VSV8, the immunodominant peptide epitope of the
      vesicular stomatitis virus, and native, purified GRP94, we have investigated
      GRP94-peptide complex formation. The formation of stable GRP94-VSV8 complexes was
      slow; competition studies demonstrated that peptide binding to GRP94 was
      specific. VSV8 binding to GRP94 was stimulated 2-fold or 4-fold, respectively,
      following chemical denaturation/renaturation or transient heat shock. The
      activation of GRP94-peptide binding occurred coincident with a stable, tertiary
      conformational change, as identified by tryptophan fluorescence and proteolysis
      studies. Analysis of GRP94 secondary structure by circular dichroism spectroscopy
      indicated an identical alpha-helical content for the native, chemically
      denatured/renatured, and heat-shocked forms of GRP94. Through use of the
      environment-sensitive fluorophores acrylodan and Nile Red, it was observed that
      the activation of peptide binding was accompanied by enhanced peptide and solvent
      accessibility to a hydrophobic binding site(s). Peptide binding to native or
      activated GRP94 was identical in the presence or absence of ATP or ADP. These
      results are discussed with respect to a model in which peptide binding to GRP94
      occurs within a hydrophobic binding pocket whose accessibility is
      conformationally regulated in an adenine nucleotide-independent manner.

PMID- 9548958
TI  - Modulation of lipid polymorphism by the feline leukemia virus fusion peptide:
      implications for the fusion mechanism.
AB  - The structural effects of the fusion peptide of feline leukemia virus (FeLV) on
      lipid polymorphism were studied, using differential scanning calorimetry (DSC),
      31P nuclear magnetic resonance (NMR), and time-resolved X-ray diffraction. This
      peptide lowers the bilayer to inverted hexagonal phase transition temperature,
      TH, of dipalmitoleoylphosphatidylethanolamine (DiPoPE) at peptide mole fractions
      of up to 1.5 x 10(-3) at pH 5.0 and at pH 7.4. The temperature at which isotropic
      31P NMR signals for monomethyldioleoylphosphatidylethanolamine (MeDOPE) first
      occurred is lowered by the FeLV peptide. The amount of isotropic signal seen at
      40 degrees C is directly correlated to the peptide:lipid molar ratio. In the
      peptide-containing samples, more lipid remains in the isotropic state over the
      whole recorded temperature range. Isotropic 31P NMR signals were observed for
      DiPoPE in the presence of the FeLV peptide for the entire recorded temperature
      range of 35-50 degrees C, while pure DiPoPE showed no significant amount of
      isotropic signal. X-ray studies of DiPoPE show the formation of a new lipid phase
      with peptide, which is not seen in the pure lipid samples. Disordering of the
      Lalpha phase is evidenced by broadening of the diffraction peaks, and the
      hexagonal cell parameter is decreased with peptide present. Our results suggest
      that the FeLV peptide is increasing the negative curvature of the lipid system,
      which is thought to be crucial to the formation of highly bent, high-energy
      structural fusion intermediates, such as the "stalk" model. Fusion activity for
      this putative fusogenic peptide was also demonstrated, using a resonance energy
      transfer (RET) lipid mixing assay. To our knowledge, this work provides the first
      published experimental evidence of both fusogenic activity and effects on lipid
      polymorphism for the FeLV fusion peptide.

PMID- 9548959
TI  - Alpha 1-adrenergic receptor subtype determinants for 4-piperidyl oxazole
      antagonists.
AB  - Mutational studies in conjunction with ligand binding assays were used to examine
      the basis of alpha1-adrenergic receptor subtype selectivity for a series of 4
      piperidyloxazole antagonists. A set of chimeric alpha 1A receptors were created
      by systematically substituting individual transmembrane domains from alpha 1D
      adrenergic receptors. The oxazole antagonists exhibited significant reductions in
      affinity against the receptor construct alpha 1A/D(TM2), and moderate reductions
      in affinity versus constructs alpha 1A/D(TM5), alpha 1A/B(TM5), and alpha
      1A/D(TM6). Antagonist affinities for these chimeras exceeded those found for wild
      type alpha 1D and alpha 1B. Site-directed mutagenesis methods were then used to
      explore the role that individual residues in TM2 and TM5 play in ligand binding
      affinity and selectivity. These studies revealed that mutations at position 86 in
      the second transmembrane domain and position 185 in the fifth transmembrane
      domain of the alpha 1A receptor have a major impact on receptor subtype
      selectivity.

PMID- 9548960
TI  - Phosphoinositide 3-kinase in rat liver nuclei.
AB  - Biochemical and immunochemical data from the present investigation reveal the
      existence of a p85/p110 phosphoinositide 3-kinase (PI 3-kinase) in rat liver
      nuclei. 32P-Labeling of membrane phosphoinositides by incubating intact nuclei
      with [gamma-32P]ATP results in the formation of [32P]phosphatidyl-inositol 3,4, 5
      trisphosphate [PtdIns(3,4,5)P3], accompanied by small quantities of
      [32P]phosphatidylinositol 3-phosphate [PtdIns(3)P]. Studies with subnuclear
      fractions indicate that the PI 3-kinase is not confined to nuclear membranes. The
      nuclear soluble fraction also contains PI 3-kinase and an array of inositide
      metabolizing enzymes, including phospholipase C (PLC), phosphoinositide
      phosphatase, and diacylglycerol (DAG) kinase. As a result, exposure of
      phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] to the nuclear extract in
      the presence of [gamma-32P]ATP generates a series of 32P-labeled D-3
      phosphoinositides and phosphatidic acid (PA) in an interdependent manner. On the
      basis of the immunological reactivity and kinetic behavior, the nuclear PI 3
      kinase is analogous, if not identical, to PI 3-kinase alpha, and constitutes
      about 5% of the total PI 3-kinase in the cell. Moreover, we test the premise that
      nuclear PI 3-kinase may, in part, be regulated through the control of substrate
      availability by PtdIns(4,5)P2-binding proteins. Effect of CapG, a nuclear actin
      regulatory protein, on PI 3-kinase activity is examined in view of its unique
      Ca2+-dependent PtdIns(4, 5)P2-binding capability. In vitro data show that the
      CapG-mediated inhibition of nuclear PI 3-kinase is prompted by PKC
      phosphorylation of CapG and elevated [Ca2+]. This CapG-dependent regulation
      provides a plausible link between nuclear PLC and PI 3-kinase pathways for cross
      communications. Taken together, these findings provide definite data concerning
      the presence of an autonomous PI 3-kinase cycle in rat liver nuclei. The nuclear
      location of PI 3-kinase may lead to a better understanding regarding its
      functional role in transducing signals from the plasma membrane to the nucleus in
      response to diverse physiological stimuli.

PMID- 9548961
TI  - Epimerization via carbon-carbon bond cleavage. L-ribulose-5-phosphate 4-epimerase
      as a masked class II aldolase.
AB  - Studies indicating that the E. coli L-ribulose-5-phosphate 4-epimerase employs an
      "aldolase-like" mechanism are reported. This NAD+-independent enzyme epimerizes a
      stereocenter that does not bear an acidic proton and therefore it cannot utilize
      a simple deprotonation-reprotonation mechanism. Sequence similarities between the
      epimerase and the class II l-fuculose-1-phosphate aldolase suggest that the two
      may be evolutionarily related and that the epimerization may occur via carbon
      carbon bond cleavage and re-formation. Conserved residues thought to provide the
      metal ion ligands of the epimerase have been modified using site-directed
      mutagenesis. The resulting mutants show low kcat values in addition to a reduced
      affinity for Zn2+. These observations serve to establish that there is a
      structural link between between the active site geometry of the epimerase and the
      aldolase. In addition, the H97N mutant was found to catalyze the condensation of
      dihydroxyacetone and glycolaldehyde phosphate to produce a mixture of L-ribulose
      5-phosphate and D-xylulose-5-phosphate. This observation of aldolase activity
      establishes that the epimerase active site is capable of promoting carbon-carbon
      bond cleavage. Furthermore, glycolaldehyde phosphate was shown to be a
      competitive inhibitor of the mutant enzyme (KI = 0.37 mM) but not of the wild
      type enzyme. The mutation apparently causes the epimerase to become "leaky" and
      enables it to bind/generate the normal reaction intermediates from the unbound
      aldol cleavage products.

PMID- 9548962
TI  - General base catalysis by the phosphatidylcholine-preferring phospholipase C from
      Bacillus cereus: the role of Glu4 and Asp55.
AB  - To assess what roles the active site residues Glu4 and Asp55 of the
      phosphatidylcholine-preferring phospholipase C of Bacillus cereus (PLCBc) might
      play in binding and catalysis, selected mutants were prepared through site
      directed mutagenesis of the plc gene. The mutants were then expressed in
      Escherichia coli and purified as fusion proteins with the maltose binding protein
      (MBP). Kinetic analysis showed that mutations at Glu4 had only modest effects on
      the catalytic activity, whereas those at Asp55 led to proteins whose values for
      kcat/KM were 10(4)-10(6) times less than that of the wild-type enzyme. The modest
      decrease in catalytic activity and the pH-dependent profile of the E4L mutant
      strongly suggest that glutamic acid at position 4 is not the general base in the
      PLCBc-catalyzed reaction. Rather, the results support the hypothesis that Glu4 is
      primarily involved in substrate binding, perhaps by electrostatic stabilization
      of the positive charge of the choline moiety of the phosphatidylcholine
      substrate. Examination of X-ray crystallographic data of PLCBc and its various
      complexes reveals that the carboxylate side chain of Asp55 is positioned such
      that it could activate a water for nucleophilic attack on the substrate or serve
      as a ligand for Zn1. However, the involvement of the side chain of Asp55 as an
      important Zn1 ligand is not consistent with the atomic absorption and
      thermostability data obtained for the D55L mutant, which are virtually identical
      with that of the wild-type enzyme. The large reduction in the measured kcat/KM of
      the D55E, D55N, and D55L mutants of PLCBc indicates that Asp55 plays a critical
      role in catalysis and likely serves as the general base in the hydrolysis of
      phosphatidylcholine by PLCBc.

PMID- 9548963
TI  - Coexisting kinetically distinguishable forms of dialkylglycine decarboxylase
      engendered by alkali metal ions.
AB  - The pyridoxal phosphate (PLP) dependent enzyme dialkylglycine decarboxylase (DGD)
      specifically binds alkali metal ions near the active site. Large ions (Rb+, K+)
      activate the enzyme while smaller ones (Na+, Li+) inhibit it. Crystallographic
      results have shown that DGD undergoes a metal ion size dependent structural
      switch [Hohenester, E., Keller, J. W., and Jansonius, J. N. (1994) Biochemistry
      33, 13561], but no evidence for multiple conformations in crystalline DGD was
      obtained. Here, evidence is presented that DGD-K+ in solution exists in two
      conformations differing in catalytic competence. Initial rate traces for DGD-K+
      exhibit a high degree of curvature due to decreasing activity over time. DGD
      remains tetrameric under the assay conditions as demonstrated by gel filtration
      experiments, arguing against the possibility of subunit dissociation as the
      source of activity loss. Likewise, the mass spectrum of DGD shows a single
      covalent form. A hysteretic model that assumes two slowly interconverting enzyme
      forms accounts well for the initial rate data when kinetic parameters from
      biphasic pre-steady-state kinetics are employed. The fit of the model to the data
      yields an estimate of 59 +/- 1% for the fast form. A cooperative model cannot
      account for the data. Double reciprocal plots for coenzyme binding to DGD exhibit
      two linear phases. Similarly, two kinetic phases are observed in PLP association
      kinetics. The substitution of Na+ or Rb+ for K+ alters the steady-state kinetic
      parameters of DGD. Preincubation of DGD-K+ with the competitive inhibitor 1
      aminocyclopropane-1-carboxylate (ACC) lowers both kcat and KAIB apparently by
      drawing the enzyme toward the less active, tighter binding form observed in the
      pre-steady-state kinetics. These results suggest that the structure of the
      protein around the alkali metal ion determines the conformational distribution.
      The transamination reaction with l-alanine was coupled in the pre-steady-state to
      the LDH-catalyzed oxidation of NADH. This experiment yields an estimate of 68 +/-
      4% for the fast form, in agreement with the hysteretic fit to the steady-state
      data. The reaction of DGD with dithiobis(nitrobenzoate) was used to probe the
      preexisting forms of DGD. Preincubation of DGD with ACC, like the exchange of Na+
      for K+, shifts the conformational distribution, in agreement with the steady
      state kinetics. These experiments clearly demonstrate that DGD is a hysteretic
      enzyme whose conformational distribution is controlled by the identity of the
      alkali metal ion bound near the active site, and that cooperativity does not play
      a role in catalysis or regulation.

PMID- 9548964
TI  - Assessment of the role of an omega loop of cholesterol oxidase: a truncated loop
      mutant has altered substrate specificity.
AB  - The function of an active site loop (70-90) of cholesterol oxidase has been
      ascertained by deleting five contiguous residues (79-83) from the tip of the
      loop. From the crystal structure of the wild-type enzyme, it appears that this
      truncation will not significantly perturb the structure of the rest of the
      enzyme. The UV/vis and CD spectra of the mutant confirm that the enzyme is
      properly folded with FAD bound. The mutant enzyme still transfers 2H from the
      4beta-carbon of the intermediate, cholest-5-en-3-one, to the 6beta-carbon of the
      product, cholest-4-en-3-one, during isomerization. The kcat/Km of the mutant is
      increased 6-fold with dehydroepiandrosterone as substrate. Thus, the enzyme is
      still catalytically active after deletion of the five loop-tip residues. With
      micellar cholesterol, the kcat/Km of the mutant is decreased 170-fold relative to
      wild type. This suggests that the tip of the loop is necessary for packing with
      the "tail" of cholesterol and is responsible for substrate specificity at C17.
      Increased release of intermediate cholest-5-en-3-one in the mutant-catalyzed
      reaction is not observed. Truncation of the loop, therefore, does not affect the
      grip of the enzyme on the intermediate. With lipid vesicle substrates (egg
      phosphatidylcholine/cholesterol, 1:1), the initial velocity of the mutant is
      reduced 3000-fold. The binding affinity for the vesicles, however, is only
      reduced 2-fold. Consequently, the loop is not the primary determinant of binding
      affinity for vesicles. It is concluded that the loop is important for movement of
      cholesterol from the lipid bilayer. The tip residues form a hydrophobic pathway
      between lipid membrane and active site to facilitate movement of substrate and
      product in to and out of the active site.

PMID- 9548965
TI  - Genetics of disease.

PMID- 9548967
TI  - The beautifully simple but intriguingly complex world of small genomes.

PMID- 9548968
TI  - WebWise: guide to the Institute of Molecular Biology Genome Sequencing Center
      Jena web site.

PMID- 9548969
TI  - The context of human genetic evolution.
AB  - The debate on modern human origins has often focused on the relationship between
      genes and fossils. Although more and more genetic evidence has been accumulating
      in favor of a recent African origin for modern humans, it has been assumed by
      many that the fossil evidence remains ambiguous. On the contrary, it has been
      clear for some time that the fossil evidence does not support the multiregional
      model: Fossils and archeology indicate a pattern of multiple dispersals from and
      beyond Africa, against which the genetic data can be compared. The continuing
      value of paleobiology is in complementing genetic information by revealing the
      context of human evolution: locating the dispersals and extinctions of
      populations in time and space, correlating these events with the environmental
      forces that shaped them, and providing an increasingly detailed understanding of
      the morphology and technology of early humans.

PMID- 9548970
TI  - New insulin-like proteins with atypical disulfide bond pattern characterized in
      Caenorhabditis elegans by comparative sequence analysis and homology modeling.
AB  - We have identified three new families of insulin homologs in Caenorhabditis
      elegans. In two of these families, concerted mutations suggest that an additional
      disulfide bond links B and A domains, and that the A-domain internal disulfide
      bond is substituted by a hydrophobic interaction. Homology modeling remarkably
      confirms these predictions and shows that despite this atypical disulfide bond
      pattern and the absence of C-like peptide, all these proteins may adopt the same
      fold as the insulin. Interestingly, whereas we identified 10 insulin-like
      peptides, only one insulin-like-receptor (daf-2) has been found. We propose that
      these insulin-related peptides may correspond to different activators or
      inhibitors of the daf-2 insulin-regulating pathway.

PMID- 9548971
TI  - Multiple members of a third subfamily of P-type ATPases identified by genomic
      sequences and ESTs.
AB  - The Saccharomyces cerevisiae genome contains five P-type ATPases divergent from
      both of the well-known subfamilies of these membrane ion transporters. This newly
      recognized third subfamily can be further divided into four classes of genes with
      nearly equal relatedness to each other. Genes of this new subfamily are also
      present and expressed in multicellular organisms such as Caenorhabditis elegans
      and mammals; some, but not all, can be assigned to the classes identified in
      yeast. Different classes of genes and different genes within a class are
      expressed differentially in tissues of the mouse. The recently cloned gene for
      the mammalian aminophospholipid translocase belongs to this new subfamily,
      suggesting that other subfamily members may transport other lipids or lipid-like
      molecules from one leaflet of the membrane bilayer to the other.

PMID- 9548972
TI  - Analysis of EST-driven gene annotation in human genomic sequence.
AB  - We have performed a systematic analysis of gene identification in genomic
      sequence by similarity search against expressed sequence tags (ESTs) to assess
      the suitability of this method for automated annotation of the human genome. A
      BLAST-based strategy was constructed to examine the potential of this approach,
      and was applied to test sets containing all human genomic sequences longer than 5
      kb in public databases, plus 300 kb of exhaustively characterized benchmark
      sequence. At high stringency, 70%-90% of all annotated genes are detected by near
      identity to EST sequence; >95% of ESTs aligning with well-annotated sequences
      overlap a gene. These ESTs provide immediate access to the corresponding cDNA
      clones for follow-up laboratory verification and subsequent biologic analysis. At
      lower stringency, up to 97% of annotated genes were identified by similarity to
      ESTs. The apparent false-positive rate rose to 55% of ESTs among all sequences
      and 20% among benchmark sequences at the lowest stringency, indicating that many
      genes in public database entries are unannotated. Approximately half of the
      alignments span multiple exons, and thus aid in the construction of gene
      predictions and elucidation of alternative splicing. In addition, ESTs from
      multiple cDNA libraries frequently cluster over genes, providing a starting point
      for crude expression profiles. Clone IDs may be used to form EST pairs, and
      particularly to extend models by associating alignments of lower stringency with
      high-quality alignments. These results demonstrate that EST similarity search is
      a practical general-purpose annotation technique that complements pattern
      recognition methods as a tool for gene characterization.

PMID- 9548973
TI  - Characterization and comparison of the human and mouse GLC1A glaucoma genes.
AB  - The GLC1A gene (which encodes the protein myocilin) has been associated with the
      development of primary open angle glaucoma. Bacterial artificial chromosomes
      containing the human GLC1A gene and its mouse ortholog were subcloned and
      sequenced to reveal the genomic structure of the genes. Comparison of the coding
      sequences of the human and mouse GLC1A genes revealed a high degree of amino acid
      homology (82%) and the presence of several conserved motifs in the predicted
      GLC1A proteins. The expression of GLC1A was examined by Northern blot analysis of
      RNA from adult human tissues. GLC1A expression was observed in 17 of 23 tissues
      tested, suggesting a wider range of expression than was recognized previously.
      The comparison of the human and mouse GLC1A genes suggests that the mouse may be
      a useful model organism in studying the molecular pathophysiology of glaucoma.

PMID- 9548974
TI  - Bacterial contig map of the 21q11 region associated with Alzheimer's disease and
      abnormal myelopoiesis in Down syndrome.
AB  - We present a high-resolution bacterial contig map of 3.4 Mb of genomic DNA in
      human chromosome 21q11-q21, encompassing the region of elevated disomic
      homozygosity in Down Syndrome-associated abnormal myelopoiesis and leukemia, as
      well as the markers, which has shown a strong association with Alzheimer's
      Disease that has never been explained. The map contains 89 overlapping PACs,
      BACs, or cosmids in three contigs (850, 850, and 1500 kb) with two gaps (one of
      140-210 kb and the second <5 kb). To date, eight transcribed sequences derived by
      cDNA selection, exon trapping, and/or global EST sequencing have been positioned
      onto the map, and the only two genes so far mapped to this cytogenetic region,
      STCH and RIP140 have been precisely localized. This work converts a further 10%
      of chromosome 21q into a high-resolution bacterial contig map, which will be the
      physical basis for the long-range sequencing of this region. The map will also
      enable positional derivation of new transcribed sequences, as well as new
      polymorphic probes, that will help in elucidation of the role the genes in this
      region may play in abnormal myelopoiesis and leukemia associated with trisomy 21
      and Alzheimer's Disease.

PMID- 9548975
TI  - Xenoduplex analysis--a method for comparative gene mapping using hybrid panels.
AB  - Somatic cell hybrid (SCH) panels and radiation hybrid (RH) panels are powerful
      resources for comparative gene mapping because gene assignments are made without
      the detection of genetic polymorphism as needed for linkage mapping. A frequently
      encountered problem, however, is that the gene specific primers may amplify
      homologous PCR products of equal length from the donor and recipient species of
      the panel. Here, we describe a simple solution to this problem in which we
      utilize the formation of interspecies heteroduplexes that can be easily
      distinguished from the corresponding homoduplexes by native polyacrylamide gel
      electrophoresis. We denote these DNA-DNA interspecies hybrids, xenoduplexes (xeno
      = Gr. Xenos, foreigner). A merit of the method is that the formation of
      xenoduplexes strongly suggests that the PCR products from the two species
      represent homologous sequences. The method is thus particularly useful for
      comparative gene mapping when the PCR primers have been designed by use of
      sequence information from other species. In this study we have successfully used
      xenoduplex analysis and a pig-rodent SCH panel to map seven porcine genes (ACADM,
      AT3, HOXD, IL8RB, LEPR, PAX8, PKLR) for which no previous sequence information
      was available. The assignment of the leptin receptor gene (LEPR) to pig
      chromosome 6q32-35 excluded LEPR as a candidate gene for a QTL on pig chromosome
      4 with a major effect on fatness.

PMID- 9548976
TI  - Modification of bacterial artificial chromosome clones using Cre recombinase:
      introduction of selectable markers for expression in eukaryotic cells.
AB  - Bacterial artificial chromosome clones (BACs) are widely used at present in human
      genome physical mapping projects. To extend the utility of these clones for
      functional genomic studies, we have devised a method to modify BACs using Cre
      recombinase to introduce a gene cassette into the loxP sequence, which is present
      in the vector portion of the BAC clone. Cre-mediated integration is site specific
      and thus maintains the integrity of the genomic insert sequences, while
      eliminating the steps that are involved in restriction digest-based DNA cloning
      strategies. The success of this method depends on the use of a DNA construct,
      RETRObac, which contains the reporter marker green fluorescent protein (GFP) and
      the selectable marker neomycin phosphotransferase (neo), but does not contain a
      bacterial origin of replication. BAC clones have been modified successfully using
      this method and the genomic insert shows no signs of deletions or rearrangements.
      Transfection efficiencies of the modified BACs into human or murine cell lines
      ranged from 1% to 6%. After culture in media containing G418 for 3 weeks,
      approximately 0. 1% of cells previously sorted for GFP expression acquired stable
      antibiotic resistance. Introduction of a human BAC clone that contains genomic
      p53 sequences into murine NIH3T3 cells led to expression of human p53 mRNA as
      determined by RT-PCR, demonstrating that sequences contained on the BAC are
      expressed. We believe that GFP-neo modified BAC clones will be a valuable
      resource in efforts to study biological effects of known genes as well as in
      efforts to clone and analyze new genes and regulatory regions.

PMID- 9548977
TI  - Endosperm developments 

PMID- 9548978
TI  - Cell-to-cell and phloem-mediated transport of potato virus X. The role of virions
AB  - Movement-deficient potato virus X (PVX) mutants tagged with the green fluorescent
      protein were used to investigate the role of the coat protein (CP) and triple
      gene block (TGB) proteins in virus movement. Mutants lacking either a functional
      CP or TGB were restricted to single epidermal cells. Microinjection of dextran
      probes into cells infected with the mutants showed that an increase in the
      plasmodesmal size exclusion limit was dependent on one or more of the TGB
      proteins and was independent of CP. Fluorescently labeled CP that was injected
      into epidermal cells was confined to the injected cells, showing that the CP
      lacks an intrinsic transport function. In additional experiments, transgenic
      plants expressing the PVX CP were used as rootstocks and grafted with
      nontransformed scions. Inoculation of the PVX CP mutants to the transgenic
      rootstocks resulted in cell-to-cell and systemic movement within the transgenic
      tissue. Translocation of the CP mutants into sink leaves of the nontransgenic
      scions was also observed, but infection was restricted to cells close to major
      veins. These results indicate that the PVX CP is transported through the phloem,
      unloads into the vascular tissue, and subsequently is transported between cells
      during the course of infection. Evidence is presented that PVX uses a novel
      strategy for cell-to-cell movement involving the transport of filamentous virions
      through plasmodesmata.

PMID- 9548979
TI  - Endosperm development after fusion of isolated, single maize sperm and central
      cells in vitro 
AB  - We demonstrate here the possibility of endosperm development in vitro after the
      fusion of pairs of an isolated sperm and an isolated central cell of maize. The
      occurrence of karyogamy and the time course of the fusion of sperm and central
      cell nuclei are presented. The fusion of the sperm nucleus occurred either with
      one of the two polar nuclei or with the secondary nucleus and was completed
      within 2 hr after in vitro cell fusion. The in vitro study of early events after
      cell and nuclear fusion indicates that the resulting primary endosperm cell
      develops into a characteristic tissue capable of self-organization apart from the
      mother tissue. The technology presented here opens the way for new cellular and
      molecular studies, especially of early events after sperm and central cell
      fusion. These studies should lead to a better understanding of the processes of
      double fertilization and endosperm development.

PMID- 9548980
TI  - The movement protein of cucumber mosaic virus traffics into sieve elements in
      minor veins of nicotiana clevelandii 
AB  - The location of the 3a movement protein (MP) of cucumber mosaic virus (CMV) was
      studied by quantitative immunogold labeling of the wild-type 3a MP in leaves of
      Nicotiana clevelandii infected by CMV as well as by using a 3a-green fluorescent
      protein (GFP) fusion expressed from a potato virus X (PVX) vector. Whether
      expressed from CMV or PVX, the 3a MP targeted plasmodesmata and accumulated in
      the central cavity of the pore. Within minor veins, the most extensively labeled
      plasmodesmata were those connecting sieve elements and companion cells. In
      addition to targeting plasmodesmata, the 3a MP accumulated in the parietal layer
      of mature sieve elements. Confocal imaging of cells expressing the 3a-GFP fusion
      protein showed that the 3a MP assembled into elaborate fibrillar formations in
      the sieve element parietal layer. The ability of 3a-GFP, expressed from PVX
      rather than CMV, to enter sieve elements demonstrates that neither the CMV RNA
      nor the CMV coat protein is required for trafficking of the 3a MP into sieve
      elements. CMV virions were not detected in plasmodesmata from CMV-infected
      tissue, although large CMV aggregates were often found in the parietal layer of
      sieve elements and were usually surrounded by 3a MP. These data suggest that CMV
      traffics into minor vein sieve elements as a ribonucleoprotein complex that
      contains the viral RNA, coat protein, and 3a MP, with subsequent viral assembly
      occurring in the sieve element parietal layer.

PMID- 9548981
TI  - The organization and evolution of the spinach stress 70 molecular chaperone gene
      family.
AB  - The stress 70 molecular chaperones of plants are localized and function in all of
      the major subcellular compartments of the cell. Collectively, all of the various
      forms are encoded by a multigene family in the nucleus. At least 12 members of
      this family have been found, and sequence and DNA blot analyses provide an
      emerging description of the diversity of gene structure organization for this
      family of evolutionarily conserved proteins in spinach. They exhibit not only
      structural diversity in the organization of coding and noncoding regions but also
      distinct expression patterns for different tissues and abiotic conditions. The
      results of phylogenetic analyses are concordant with at least four major
      evolutionary events that gave rise to stress 70 molecular chaperones in each of
      four major subcellular compartments of plant cells: the plastid, mitochondrion,
      cytoplasm, and endoplasmic reticulum. The varied expression patterns also
      illustrate the complexity of effectively interpreting the role of any one of
      these stress-related proteins in response to abiotic stress in the absence of
      context to the other members of the family.

PMID- 9548983
TI  - Induction of kranz anatomy and C4-like biochemical characteristics in a submerged
      amphibious plant by abscisic acid 
AB  - The amphibious leafless sedge Eleocharis vivipara develops C4-like traits as well
      as Kranz anatomy under terrestrial conditions, but it develops C3-like traits
      without Kranz anatomy under submerged conditions. When submerged plants are
      exposed to aerial conditions, they rapidly produce new photosynthetic tissues
      with C4-like traits. In this study, experiments were performed to determine
      whether abscisic acid (ABA), a plant stress hormone, could induce the formation
      of photosynthetic tissues with Kranz anatomy and C4-like biochemical traits under
      water in the submerged form. When the submerged plants were grown in water
      containing 5 &mgr;M ABA, they developed new photosynthetic tissues with Kranz
      anatomy, forming well-developed Kranz (bundle sheath) cells that contained many
      organelles. The ABA-induced tissues accumulated large amounts of
      phosphoenolpyruvate carboxylase, pyruvate orthophosphate dikinase, and NAD-malic
      enzyme at the appropriate cellular sites. The tissues had 3.4 to 3.8 times more
      C4 enzyme activity than did tissues of the untreated submerged plants. Carbon-14
      pulse and carbon-12 chase experiments revealed that the ABA-induced tissues fixed
      higher amounts of carbon-14 into C4 compounds and lower amounts of carbon-14 into
      C3 compounds as initial products than did the submerged plants and that they
      exhibited a C4-like pattern of carbon fixation under aqueous conditions of low
      carbon, indicating enhanced C4 capacity in the tissues. This report provides an
      example of the hormonal control of the differentiation of the structural and
      functional traits required for the C4 pathway.

PMID- 9548982
TI  - Uncoupling PR gene expression from NPR1 and bacterial resistance:
      characterization of the dominant Arabidopsis cpr6-1 mutant.
AB  - In Arabidopsis, NPR1 mediates the salicylic acid (SA)-induced expression of
      pathogenesis-related (PR) genes and systemic acquired resistance (SAR). Here, we
      report the identification of another component, CPR 6, that may function with
      NPR1 in regulating PR gene expression. The dominant CPR 6-1 mutant expresses the
      SA/NPR1-regulated PR genes (PR-1, BGL 2, and PR-5) and displays enhanced
      resistance to Pseudomonas syringae pv maculicola ES4326 and Peronospora
      parasitica Noco2 in the absence of SAR induction. cpr 6-1-induced PR gene
      expression is not suppressed in the cpr 6-1 npr1-1 double mutant but is
      suppressed when SA is removed by salicylate hydroxylase. Thus, constitutive PR
      gene expression in cpr 6-1 requires SA but not NPR1. In addition, resistance to
      P. s. maculicola ES4326 is suppressed in the cpr 6-1 npr1-1 double mutant,
      despite expression of PR-1, BGL 2, and PR-5. Resistance to P. s. maculicola
      ES4326 must therefore be accomplished through unidentified antibacterial gene
      products that are regulated through NPR1. These results show that CPR 6 is an
      important regulator of multiple signal transduction pathways involved in plant
      defense.

PMID- 9548984
TI  - Role of calcium in signal transduction during the hypersensitive response caused
      by basidiospore-derived infection of the cowpea rust fungus 
AB  - The hypersensitive response (HR) of disease-resistant plant cells to fungal
      invasion is a rapid cell death that has some features in common with programmed
      cell death (apoptosis) in animals. We investigated the role of cytosolic free
      calcium ([Ca2+]i) in the HR of cowpea to the cowpea rust fungus. By using
      confocal laser scanning microscopy in conjunction with a calcium reporter dye, we
      found a slow, prolonged elevation of [Ca2+]i in epidermal cells of resistant but
      not susceptible plants as the fungus grew through the cell wall. [Ca2+]i levels
      declined to normal levels as the fungus entered and grew within the cell lumen.
      This elevation was related to the stage of fungal growth and not to the speed of
      initiation of subsequent cell death. Elevated [Ca2+]i levels also represent the
      first sign of the HR detectable in this cowpea-cowpea rust fungus system. The
      increase in [Ca2+]i was prevented by calcium channnel inhibitors. This effect was
      consistent with pharmacological tests in which these inhibitors delayed the HR.
      The data suggest that elevation of [Ca2+]i is involved in signal transduction
      leading to the HR during rust fungal infection.

PMID- 9548985
TI  - A glycoprotein modified with terminal N-acetylglucosamine and localized at the
      nuclear rim shows sequence similarity to aldose-1-epimerases.
AB  - Several glycoproteins that are present at the nuclear rim and at the nuclear pore
      complex of tobacco suspension-cultured cells are modified by O-linked
      oligosaccharides with terminal N-acetylglucosamine (GlcNAc). Here, we report on
      the purification of several of these glycoproteins, which are referred to as
      terminal GlcNAc (tGlcNAc) proteins. In vitro galactosylation of the tGlcNAc
      proteins generated glycoproteins with terminal galactosyl-beta-1, 4-GlcNAc and
      thus permitted their isolation by Erythrina crystagalli agglutinin affinity
      chromatography. Peptide sequence information derived from one tGlcNAc protein
      with an apparent molecular mass of 40 to 43 kD, designated gp40, made it possible
      to clone its gene. Interestingly, gp40 has 28 to 34% amino acid identity to
      aldose-1-epimerases from bacteria, and no gene encoding an aldose-1-epimerase has
      been isolated previously from higher organisms. Polyclonal antibodies were
      generated against recombinant gp40. Consistent with its purification as a
      putative nuclear pore complex protein, gp40 was localized to the nuclear rim, as
      shown by biochemical fractionation and immunofluorescence microscopy.

PMID- 9548986
TI  - Expression of lauroyl-acyl carrier protein thioesterase in brassica napus seeds
      induces pathways for both fatty acid oxidation and biosynthesis and implies a set
      point for triacylglycerol accumulation 
AB  - Expression of a California bay lauroyl-acyl carrier protein thioesterase (MCTE)
      in developing seeds of transgenic oilseed rape alters the fatty acid composition
      of the mature seed, resulting in up to 60 mol% of laurate in triacylglycerols. In
      this study, we examined the metabolism of lauric acid and 14C-acetate in
      developing seeds of oilseed rape that express high levels of MCTE. Lauroyl-CoA
      oxidase activity but not palmitoyl-CoA oxidase activity was increased several
      fold in developing seeds expressing MCTE. In addition, isocitrate lyase and
      malate synthase activities were six- and 30-fold higher, respectively, in high
      laurate developing seeds. Control seeds incorporated 14C-acetate almost entirely
      into fatty acids, whereas in seeds expressing MCTE, only 50% of the label was
      recovered in lipids and the remainder was in a range of water-soluble components,
      including sucrose and malate. Together, these results indicate that the pathways
      for beta-oxidation and the glyoxylate cycle have been induced in seeds expressing
      high levels of MCTE. Although a substantial portion of the fatty acid produced in
      these seeds is recycled to acetyl-CoA and sucrose through the beta-oxidation and
      glyoxylate cycle pathways, total seed oil is not reduced. How is oil content
      maintained if lauric acid is inefficiently converted to triacylglycerol? The
      levels of acyl carrier protein and several enzymes of fatty acid synthesis were
      increased two- to threefold at midstage development in high-laurate seeds. These
      results indicate that a coordinate induction of the fatty acid synthesis pathway
      occurs, presumably to compensate for the lauric acid lost through beta-oxidation
      or for a shortage of long-chain fatty acids.

PMID- 9548987
TI  - Accumulation of an acidic dehydrin in the vicinity of the plasma membrane during
      cold acclimation of wheat 
AB  - Expression of the acidic dehydrin gene wcor410 was found to be associated with
      the development of freezing tolerance in several Gramineae species. This gene is
      part of a family of three homologous members, wcor410, wcor410b, and wcor410c,
      that have been mapped to the long arms of the homologous group 6 chromosomes of
      hexaploid wheat. To gain insight into the function of this gene family,
      antibodies were raised against the WCOR410 protein and affinity purified to
      eliminate cross-reactivity with the WCS120 dehydrin-like protein of wheat.
      Protein gel blot analyses showed that the accumulation of WCOR410 proteins
      correlates well with the capacity of each cultivar to cold acclimate and develop
      freezing tolerance. Immunoelectron microscope analyses revealed that these
      proteins accumulate in the vicinity of the plasma membrane of cells in the
      sensitive vascular transition area where freeze-induced dehydration is likely to
      be more severe. Biochemical fractionation experiments indicated that WCOR410 is a
      peripheral protein and not an integral membrane protein. These results provide
      direct evidence that a subtype of the dehydrin family accumulates near the plasma
      membrane. The properties, abundance, and localization of these proteins suggest
      that they are involved in the cryoprotection of the plasma membrane against
      freezing or dehydration stress. We propose that WCOR410 plays a role in
      preventing the destabilization of the plasma membrane that occurs during
      dehydrative conditions.

PMID- 9548988
TI  - Estimating the time between drinking and death from tissue distribution patterns
      of ethanol.
AB  - To establish a method for estimating the time between the last consumption of
      alcohol and death, we examined the ethanol levels in body fluids and tissues of
      rats that had been orally administered 1 g/kg ethanol. We observed the following
      relationships between ethanol levels in the cardiac blood (blood in the heart
      itself), vitreous humor, and urine: cardiac blood > vitreous humor > urine at 10
      min (early absorption stage); vitreous humor > cardiac blood > urine from 20 to
      50 min (late absorption stage); vitreous humor > urine > cardiac blood from 60 to
      120 min (distribution stage); and urine > vitreous humor > cardiac blood at 180
      min (excretion stage). It was also observed that, in cases of death immediately
      following drinking, ethanol levels in the stomach contents are very high, and the
      following ratios of ethanol levels were observed: skeletal muscle to cardiac
      blood--less than 1; liver to cardiac blood--around 1. buccal mucosa to cardiac
      blood-greater than 1. These ratios at equilibrium after drinking were around 1,
      lower than 1 and around 1, respectively. We also measured alcohol levels in the
      cardiac blood, urine, vitreous humor and stomach contents of nine cadavers who
      had consumed alcohol prior to death. The relationships between the time since
      last consumption of alcohol and relative ethanol levels in these specimens were
      in good accordance with the results of the animal experiments.

PMID- 9548989
TI  - Effects of antineoplastics, antibiotics and antidiabetics on acetaldehyde
      metabolism after alcohol ingestion.
AB  - The main purpose of this study was to evaluate the inhibitory effects of 5
      fluorouracil antineoplastics, cephem antibiotics containing the
      methyltetrazolylthiol (MTT) group and antidiabetics on aldehyde dehydrogenase
      (ALDH) activity in vivo and in vitro. In in vivo experiments, rats were given a
      100 mg/kg dose of drugs (10 mg/kg for glibenclamide) orally or intraperitoneally.
      When each drug was administered singly immediately after an oral administration
      of 1.5 g/kg ethanol, only carmofur, an antineoplastic, produced marked increases
      in blood acetaldehyde concentrations. This action was also noted when ethanol was
      ingested 15 h after administration. The remaining drugs did not increase blood
      acetaldehyde concentrations. When rats were treated with carmofur at 12 h
      intervals for 3 consecutive days and were given 1.5 g/kg ethanol after the final
      treatment, blood acetaldehyde concentrations were elevated more significantly
      than with a single administration of carmofur. Furthermore, daily administration
      of cephem antibiotics containing the MTT group, latamoxef, cefamandole,
      cefoperazone and cefbuperazone, significantly increased blood acetaldehyde
      concentrations. Daily administration of sulfonylurea antidiabetics,
      chlorpropamide and acetohexamide, slightly increased blood acetaldehyde
      concentrations. Drugs causing increases in blood acetaldehyde concentrations when
      administration was combined with ethanol ingestion also inhibited ALDH activity
      in vitro. The results of the in vitro experiments roughly correlated with those
      of the in vivo experiments. The inhibitory effects of drugs on ALDH activity were
      in the following order: carmofur >> cephem antibiotics containing the MTT group >
      sulfonylurea antidiabetics.

PMID- 9548990
TI  - Fibrous structure and connection surrounding the metacarpophalangeal joint.
AB  - The fibrous components of the metacarpophalangeal (MP) joint including the palmar
      plate, the collateral ligament and the dorsal plate were studied with particular
      attention paid to the fibrous structure of the fibrous tendon sheath and the deep
      transverse metacarpal ligament. The tough fibrillar structure around the MP
      joint, especially the force nucleus, consisted of three types of mixed fibers:
      the fibrous tendon sheath of the A1 pulley, the deep transverse metacarpal
      ligament, and the palmar plate. The tendon sheath was located on the ulnar side
      in the index and middle fingers, on the central position in the ring finger, and
      on the radial side in the little finger. These fibrous connections among the
      fingers formed a transverse arch in the hand. The palmar plate of the MP joint
      was relatively rigid and appears to function as a cushion when flexed. A fold
      like protrusion of the synovial layer of the palmar plate of the MP joint had a
      meniscoid function, which was larger than that of the proximal interphalangeal
      joint. The capsule of the MP joint was thicker at the dorsal area, forming a
      dorsal plate, which is a sliding floor of the extensor mechanism and has a
      meniscoid function for joint congruity. The main lateral stabilizer consisted of
      collateral ligaments and accessory collateral ligaments anchored to the palmar
      plate. These structures act together as a "phalangeal cuff", connecting the
      proximal phalanx to the metacarpal head and stabilizing the MP joint.

PMID- 9548991
TI  - Developmental alterations of alpha-fetoprotein sugar chain in amniotic fluids
      analyzed by lectin affinity electrophoresis.
AB  - Affinity electrophoresis of human alpha-fetoprotein (AFP) in amniotic fluid from
      pregnant women between 6 to 42 weeks of gestation and in the serum of a yolk sac
      tumor was performed with concanavalin A (Con A), lentil lectin (LCA),
      erythroagglutinating phytohemagglutinin (E-PHA) and Allomyrina dichotoma lectin
      (allo A). Separated AFP bands were detected by sensitive antibody-affinity
      blotting. In the first trimester, amniotic fluid AFP showed elevated percentages
      of Con A-nonreacting AFP (AFP-C1) and LCA weakly-reacting AFP (AFP-L2) as
      previously reported. Additionally, high percentages of E-PHA strongly-reacting
      AFP (AFP-P5) and E-PHA-reacting AFP (AFP-P4) were observed. E-PHA-nonreacting AFP
      (AFP-P1), E-PHA weakly-reacting AFP (AFP-P3f), allo A-nonreacting AFP (AFP-A1)
      and asialo-AFP, AFP-A1 s, were present only in amniotic fluids from 6 to 17 weeks
      of gestation. With advancing gestation, percentages of AFP-C1, AFP-P4 and AFP-P5
      decreased and AFP-L2, AFP-P3f, AFP-A1, and AFP-A1 s disappeared by the end of 18
      weeks. The glycoforms of serum AFP of the yolk sac tumor resembled those of
      amniotic fluid AFP in the early gestational stages.

PMID- 9548992
TI  - Mast cells in osteoarthritic and rheumatoid arthritic synovial tissues of the
      human knee.
AB  - The distribution and density of mast cells in the normal and diseased synovial
      membranes were investigated. The mast cell count (MCC) in the osteoarthritic (OA)
      synovium (36.9 +/- 26.9 cells/mm2) was significantly higher than that in the
      rheumatoid arthritic (RA) synovium (18 +/- 12.3 cells/mm2). There was a marked
      positive correlation between the MCC and the volume of joint fluid in OA (r =
      0.544). There was a marked negative correlation between the MCC and the volume of
      joint fluid in RA (r = -0.478). The synovial inflammatory score had a poor
      correlation with the MCC in OA (r = 0.377) and RA (r = 0.305). No correlation was
      noted between MCC and age, sex, roentgenographic grades, disease duration, C
      reactive protein or leucocyte number in synovial fluid. Our data suggests, thus,
      that mast cells could be involved in the pathogenesis of inflammatory diseases of
      the synovium, especially in the mechanism of hydroarthrosis.

PMID- 9548993
TI  - Antibody and cytokine responses in Helicobacter pylori-infected various mouse
      strains.
AB  - Helicobacter pylori (H. pylori) infection in the stomach is etiologically closely
      associated with chronic active gastritis, peptic ulcer, gastric cancer and
      gastric mucosa-associated lymphoid tissue lymphoma. In this study, we examined
      the antibody responses and cytokine profiles of three strains of mice (BALB/c,
      C3H/He, and C57BL/6) infected with H. pylori. Following this, correlations
      between host-immune reactions and intensity of inflammation were analyzed. H.
      pylori (ATCC43504) was intragastrically administered once a week to the mice from
      4 weeks of age, and they were sacrificed at the ages of 4 and 7 months. In these
      mice, we examined the histology of the stomach, antibody titers against H.
      pylori, and serum levels of cytokines (IL-4, IL-10, TNF-alpha, IL-2 and
      Interferon-gamma). In BALB/c mice, inflammation of the stomach was minimal.
      Inflammation was observed in 63.6% of C57BL/6 mice and 33.3% of C3h/He mice. In
      C57BL/6 and C3H/He mice, all the cytokines tended to increase. In contrast,
      BALB/c mice were inactive in cytokine production except for IL-2. Two C3H/He mice
      developed severe inflammation with lymph follicles; one showed a response largely
      typical of Th-1, and the other showed a response largely typical of Th-2.
      Although a definite correlation was not shown between Th-1/Th-2 response
      evaluated by cytokine production and intensity of inflammation, it appears that
      in H. pylori-induced inflammation both cell-mediated (Th-1) and humoral (Th-2)
      immunity play a role in pathogenesis.

PMID- 9548994
TI  - Involvement of the central catecholaminergic system in nicotine-induced tail
      tremor in rats.
AB  - The effect of 6-hydroxydopamine on repeated nicotine-induced tail-tremor was
      investigated in rats. Tail-tremor induced by nicotine (0.5 mg/kg/day,
      subcutaneously) became more pronounced in intensity with daily administration for
      9 days. Rats pretreated with 6-hydroxydopamine (250 micrograms,
      intracerebroventricularly) showed almost the maximum degree of tail-tremor during
      the whole experimental period. However, in rats pretreated with 6-hydroxydopamine
      plus desipramine, enhancement of tail-tremor was slight in the beginning but
      increased with the daily nicotine administration. Fourteen-day administration of
      nicotine did not result in significant changes in noradrenaline and dopamine
      levels in the cortex, hypothalamus, striatum and nucleus accumbens. These results
      suggest that nicotine-induced tail-tremor is associated with the supersensitivity
      of postsynaptic catecholaminergic receptors in the central nervous system, and
      that the noradrenergic system may be more important than the dopaminergic system
      in this phenomenon.

PMID- 9548995
TI  - Gastrobiliary dysmotility in patients with chronic pancreatitis as assessed by a
      single noninvasive test.
AB  - We simultaneously assessed gastric emptying and gallbladder contraction after
      oral administration of a liquid meal by noninvasive ultrasonography in 17
      patients with chronic pancreatitis (CP) and in 17 healthy controls.
      Gastrointestinal (GI) transit was also assessed by a noninvasive radioopaque
      marker method. Exocrine pancreatic function was evaluated by analyzing pure
      pancreatic juice and by analyzing the autonomic nervous system by cardiovascular
      reflex tests. Patients with CP showed impaired gallbladder contraction at 15 min
      and hastened gastric emptying. The cause of the former is unclear, whereas the
      latter was closely related with decreased pancreatic lipase output, but not with
      autonomic dysfunction. GI transit time did not differ between controls and
      patients with CP. In conclusion, we succeeded in clearly demonstrating impaired
      gallbladder contraction and hastened gastric emptying in patients with CP by a
      single noninvasive test, ultrasonography. We also revealed for the first time
      that hastened gastric emptying is associated with insufficient pancreatic lipase
      output.

PMID- 9548996
TI  - Hematological manifestations in brucellosis cases in Turkey.
AB  - The hematological findings of 233 patients with brucellosis are presented and the
      possible pathologies discussed. Anemia was present in 128 patients (55%),
      leukopenia in 49 (21%) and thrombocytopenia in 59 (26%). Bone marrow aspirates of
      18 patients (8%) with pancytopenia were examined. The bone marrow was
      hypercellular in 15 and normocellular in 3 patients. Granulomatous lesions were
      detected in 12 cases (67%), and slight to moderate cytophagocytosis of
      erythrocytes, granulocytes and platelets existed in all patients. Blood cell
      counts reverted to normal within 2-3 weeks of initiating chemotherapy with
      recovery from the disease.

PMID- 9548997
TI  - Reconstruction of bone defect using the bone transport technique for a case of
      osteosarcoma of the femur.
AB  - There are few reports on skeletal reconstruction using the bone transport
      technique to repair bone defects caused by resections of tumors associated with
      osteosarcoma. We attempted to reconstruct a 23 cm bone defect after resection of
      an osteosarcoma of the left femur, and succeeded in gaining 17 cm by bone
      transport. Five years after surgery, this patient remains alive without
      metastasis or local recurrence.

PMID- 9548998
TI  - Alcohol and morality: does it matter where you live?

PMID- 9548999
TI  - Association of alcohol consumption to morality in middle-aged U.S. and Russian
      men and women.
AB  - PURPOSE: The purpose of this paper is to assess the relationships of alcohol
      consumption to total and cardiovascular disease mortality in U.S. and Russian men
      and women after adjustment for several covariates. A secondary objective is to
      determine how this relationship varies by country and gender. METHODS: Men aged
      40-59 and women aged 40-69 screened in Russia and the U.S. between 1972 and 1982
      were followed for mortality for 13 years as part of the Lipid Research Clinics
      Prevalence and Follow-up Studies. Alcohol consumption was based on a 7-day recall
      of drinks of beer, wine, mixed drinks, and liquors. Drinkers of alcohol were
      classified into four levels based on amount consumed during the recall period.
      RESULTS: Age-adjusted mortality rates were higher for non-drinkers than lower
      level drinkers in both genders and countries, and there was an indication that
      mortality rates for high level drinkers, especially in men, approached those of
      non-drinkers. When mortality rates were adjusted for other risk factors they
      remained higher for non-drinkers in U.S. men and women, but in Russia, with one
      exception, there was no difference in mortality rates between drinkers and non
      drinkers. Relative risks for cardiovascular disease mortality rates were similar
      to those of total mortality. CONCLUSIONS: Beneficial association of alcohol
      consumption and mortality may be limited depending upon the prevalence of other
      risk factors in the studied population.

PMID- 9549000
TI  - Alcohol consumption and micronutrient intake as risk factors for liver cirrhosis:
      a case-control study. The Provincial Group for the study of Chronic Liver
      Disease.
AB  - PURPOSE: The purpose of this study was to assess the relationship of alcohol
      consumption and intake of 15 selected micronutrients with risk of liver
      cirrhosis. METHODS: Data from a case-control study performed in 1989-1990 in
      central Italy involving 115 incident cases and 167 hospital controls were used.
      RESULTS: Cases and controls did not differ for mean daily intake of calories,
      carbohydrates, lipids, and proteins. Significant direct dose-response
      relationships between the intakes of vitamin A and iron and the risk cirrhosis
      were observed, while significant protective effects were obtained for the intakes
      of vitamins B2 (riboflavin) and B12. Different patterns of the joint effect of
      nutrients and alcohol were also observed. The intakes of vitamin A and iron were
      significantly associated with the risk of cirrhosis in lifetime teetotalers (odds
      ratios (OR) and 95% coincidence intervals (CI) of 33.6 (1.2-979.9) and 37.9 (1.8
      819.4) for higher intake of vitamin A and iron, respectively) and in consumers of
      < 50 g/day of alcohol (vitamin A: OR 45.0; 95% CI, (2.6-774.6); iron: OR, 73.6;
      95% CI, 4.3-999). The OR associated with intakes of vitamins B2 (riboflavin) and
      B12 were not significant for the first two categories of alcohol use, while a
      higher intake of these two vitamins reduced the risk of cirrhosis associated with
      alcohol consumption above 50 g/day; the ORs (95% CI) were 23.0 (2.7-198.9) and
      104.4 (7.2-999), respectively, for higher and lower intakes of riboflavin and
      12.8 (1.8-88.1) and 138.4 (14.0-999), respectively, for higher and lower intake
      of vitamin B12. CONCLUSION: These findings might explain at least a portion of
      the individual susceptibility to alcohol-induced liver damage.

PMID- 9549002
TI  - HIV prevalence and risk behaviors among patients attending Los Angeles County
      Tuberculosis Clinics: 1993-1996.
AB  - PURPOSE: This study aimed to describe prevalence of and risk factors for HIV
      among persons with newly diagnosed class III (confirmed) and class V (suspected)
      cases of tuberculosis (TB) patients in Los Angeles County. METHODS: HIV testing
      was performed on 1307 blood specimens after routine tests were completed at six
      TB clinics in Los Angeles County. HIV test results were matched to demographic
      and risk behavior information by use of an unlinked study methodology. RESULTS:
      The overall HIV prevalence rate was 10.8%. By demographic characteristics, the
      highest prevalence rates were observed among persons born in the United States
      (15.7%), males (14.1%), blacks (14.3%), and those aged 30-44 years (14.4%).
      Confirmed TB cases (14%) were more likely to be HIV-infected than were suspect
      cases (9.6%). Risk behaviors associated with positive HIV serostatus included the
      injection of nonprescription drugs, having sex with an injection drug user, and
      use of noninjection forms of heroin, cocaine, and tranquilizers. Men who have sex
      with men were more likely to be HIV-infected than were heterosexual males.
      CONCLUSIONS: HIV testing and counseling should be a standard of care in TB
      clinics. The observed high HIV prevalence rate reinforces the importance of
      designing prevention strategies that specifically target patients with TB.

PMID- 9549001
TI  - Prevalence of chronic disease risk and protective behaviors among American Indian
      women living on the Hopi reservation.
AB  - PURPOSE: There is a growing need for disease risk factor data for various chronic
      diseases among American Indian (AI) populations. The purpose of this study was to
      determine the prevalence of disease risk and protective behavior among AI women
      living on the Hopi reservation. METHODS: 559 randomly selected AI women 18-89
      years of age completed an interviewer-administered questionnaire which included
      questions on smoking, alcohol consumption, weight, height, and self-identified
      practices to keep healthy. RESULTS: The proportions of smoking and alcohol
      consumption were low with only 5.4% women reported currently smoking and 23.1%
      reported consuming any alcohol. Both these risk factors significantly decreased
      with age and significantly increased with higher education. The proportions who
      were overweight (body mass index (BMI) 27.3-32.2) and obese (BMI > or = 32.3)
      were 36.2% and 27.0%, respectively, and were highest in the ages 25-64 years.
      Over 80% of women reported practicing behaviors to keep healthy. Significantly
      higher proportions of older women reported practicing behaviors to keep healthy
      compared with younger women. CONCLUSIONS: To develop and evaluate programs aimed
      at decreasing rates of chronic diseases among AI populations a disease risk
      factor needs to be implemented by region and tribe.

PMID- 9549003
TI  - Can regular multivitamin/mineral supplementation modify the relation between
      maternal smoking and select adverse birth outcomes?
AB  - PURPOSE: The purpose of this study was to examine whether or not regular
      multivitamin/mineral supplementation can modify the relation between maternal
      smoking and preterm birth (gestational age < 37 weeks), very-low-birthweight
      (VLBW) (< 1500 g), moderately-low-birthweight (MLBW) (< 2499 g), or small-for
      gestational-age (SGA) (< 10th percentile of birth weight for gestational age).
      METHODS: Live birth data from the 1988 National Maternal and Infant Health Survey
      (NMIHS) were used for the analysis. Maternal smoking referred to self-reported
      average number of cigarettes smoked after recognition of pregnancy, while regular
      multivitamin/mineral supplementation referred to use of multivitamin/mineral
      supplements for at least three days per week during the three months before
      and/or after recognition of pregnancy. Sample sizes included 9402 singleton
      infants for the analysis of preterm birth, 9395 for very or moderately low
      birthweight, and 9363 for small-for-gestational-age. Odds ratios were derived
      from logistic regression analyses after adjusting for a number of demographic and
      reproductive variables. RESULTS: Major results include: 1) increased risks for
      the adverse outcomes studied were observed among smoking women; 2) no effect of
      regular multivitamin/mineral supplementation in the absence of maternal smoking
      was revealed; and 3) relative excess risks due to interaction at different
      smoking levels and overall interactions between smoking and supplementation were
      not observed. CONCLUSIONS: These results suggest that regular
      multivitamin/mineral supplementation does not minimize the adverse effects
      associated with maternal smoking.

PMID- 9549004
TI  - Community occupational structure, medical and economic resources, and coronary
      mortality among U.S. blacks and whites, 1980-1988.
AB  - PURPOSE: To examine the association between coronary heart disease (CHD)
      mortality, economic and medical resources, and county occupational structure.
      METHODS: U.S. counties were classified into five occupational structure
      categories based on the percentage of workers in white-collar occupations.
      Directly age-adjusted CHD mortality rates (from vital statistics and Census data)
      and economic and medical care data (from Census and Area Resource File data) were
      calculated for each occupational structure category. Participants were black and
      white, men and women, aged 35-64 years, in the U.S. during 1980-88. CHD mortality
      rates and economic and medical care data were compared across occupational
      structure categories. RESULTS: Among blacks, CDH rates were highest in counties
      with intermediate levels of occupational structure; rates among whites were
      inversely associated with occupational structure. Per capita levels of income and
      numbers of medical-care providers were positively associated with occupational
      structure. CONCLUSION: Strategies to improve the resources of disadvantaged
      communities and the access of black workers to local occupational opportunities
      may be important for CHD prevention in high risk populations.

PMID- 9549005
TI  - The Kidney Outcomes Prediction and Evaluation (KOPE) study: a prospective cohort
      investigation of patients undergoing hemodialysis. Study design and baseline
      characteristics.
AB  - PURPOSE: The purpose of the Kidney Outcomes Prediction and Evaluation (KOPE)
      study, was to more fully characterize the end-stage renal disease (ESRD)
      population with respect to social, psychological, and clinical characteristics,
      and to prospectively study the biomedical, social, and psychological factors that
      influence a range of ESRD outcomes in a large observational study of black and
      white patients on hemodialysis. This paper focuses on the KOPE study design as
      well as characteristics of patients at baseline. METHODS: KOPE was a prospective
      cohort investigation of patients treated at four dialysis centers in Forsyth
      County, North Carolina. Participants were interviewed at the dialysis centers,
      semi-annually over a 3 1/2 year period. Prevalent cases who were being treated
      with hemodialysis at the initiation of the study were enrolled into KOPE.
      Incident cases were subsequently enrolled as they presented to the participating
      units for hemodialysis. A total of 304 prevalent and 162 incident cases were
      enrolled into the study. The baseline health and sociodemographic characteristics
      of KOPE participants reported in this paper were obtained from medical records
      and Southeast Kidney Council data. Laboratory values taken within a 30-day
      interval around the baseline interview are also reported. RESULTS: KOPE
      participants differ from national statistics on race, age, and gender.
      Differences between KOPE participants and patients living in the region, but who
      did not participate in the study, can be explained by our recruitment criteria.
      CONCLUSIONS: KOPE will enable the characterization of the ESRD population,
      identification of factors related to poor outcomes, and identification of
      opportunities for interventions to prevent death and morbidity.

PMID- 9549006
TI  - Bayesian estimation of asthma prevalence, and comparison of exercise and
      questionnaire diagnostics in the absence of a gold standard.
AB  - PURPOSE: To estimate the sensitivities, specificities, and predictive values of
      exercise challenge and questionnaire, when these tests are used to diagnose
      asthma in children. METHODS: Participants were children, predominantly aged 6 to
      12 years, selected from three primary school grades among 18 different schools in
      Montreal. Of 1111 participants, 989 successfully completed a six-minute free
      running test at school and returned a respiratory questionnaire. A total of 952
      children had complete information that could be used for analysis. A history of
      wheezing in the past year in conjunction with a past diagnosis of asthma defined
      current asthma by questionnaire. Exercise responsiveness was defined as a > or =
      10% fall in FEV1 after a six-minute free run. As there is no perfectly accurate
      diagnostic test for asthma, we analyzed the data using a previously published
      Bayesian method that allows for the estimation of test properties when no gold
      standard test is available. RESULTS: Current asthma by questionnaire was found to
      have significantly higher specificity (94.9%, 95% credible interval (CI): 93.2
      96.5 versus 82.6%, 95% CI: 79.9-85.1) and positive predictive value (53.8%, 95%
      CI: 41.0-66.7 versus 19.2%, 95% CI: 12.3-27.8) in comparison to exercise
      challenge. While there was no statistically significant difference between the
      two tests with respect to sensitivity and negative predictive values, the
      estimates were higher for current asthma (64.4%, 95% CI: 50.9-76.6 and 96.7%, 95%
      CI: 94.6-98.1, respectively) in comparison to exercise challenge (51.3%, 95% CI:
      37.8-64.5 and 95.4%, 95% CI: 93.2-97.1, respectively). Agreement between the two
      diagnostic methods was poor and the combined use of the two tests did not
      significantly improve the likelihood of correctly identifying children with
      asthma. CONCLUSIONS: Our findings support the view that exercise testing adds
      little to a well designed questionnaire in identifying subjects with asthma in
      community based studies.

PMID- 9549007
TI  - Tools for improvement: a systematic analysis and guide to accreditation by the
      JCAHO.
AB  - By viewing the Joint Commission on Accreditation of Healthcare Organizations'
      (JCAHO) standards in the context of current accreditation practice, hospital
      librarians can understand and clarify their role in realizing their
      organization's mission, goals, and objectives. By broadening their view of the
      information function as described in the accreditation standards, health sciences
      librarians can enhance their position in the hospital's management team, improve
      health information practice, and contribute to the overall performance of the
      health care organization. The role of the librarian and the library throughout
      the entire set of standards and interrelationships with other professionals and
      units are described. Examples of ways to demonstrate conformity to the standards
      are provide. Special emphasis is placed on Standard 9, Management of Information,
      to provide guidance to the librarian undergoing JCAHO accreditation.

PMID- 9549008
TI  - Electronic reserves: the changing landscape of instructional support.
AB  - During the spring 1996 academic semester, the University of Maryland Health
      Sciences Library implemented an electronic course-reserve system as a pilot
      project with the university's School of Nursing. The pilot project has been very
      successful because of thorough planning and the effectiveness of the system,
      which enables library users to retrieve assigned readings easily. This success
      inspired the staff to begin expanding the scope of the pilot project to include
      other schools and limited remote access. This paper describes the planning and
      implementation process, the issues that needed to be resolved, the response to
      the project, and future plans. Particular attention is paid to issues of
      copyright and cost recovery.

PMID- 9549009
TI  - Positioning the library at the epicenter of the networked biomedical enterprise.
AB  - The changing economic environment in which our biomedical enterprises operate
      presents unparalleled opportunities to the profession of medical librarianship.
      Evidence-based medicine, patient empowerment, asynchronous learning networks, and
      research colaboratories each involve a new type of shared information, or access
      to information in new ways or by different people. These tasks are ones with
      which librarianship is directly involved. Librarians are therefore placed
      perfectly to provide new products and services. To position the library at the
      epicenter of the networked biomedical enterprise we must meet three challenges:
      We must align the library's business strategy with that of the larger enterprise.
      We must provide services in ways that will scale-up to enable new business
      strategies. We must measure the effectiveness of services in ways that document
      their role in supporting the enterprise.

PMID- 9549010
TI  - The relationship between journal use in a medical library and citation use.
AB  - The purpose of the study was to investigate the relationship between library
      journal use and journal citation use in the medical sciences. The six-month
      journal use study was conducted in the Library of the Veterans General Hospital
      in Taipei. The data on citation frequency and impact factors were obtained from
      Journal Citation Reports, 1993 microfiche edition. The study explored the use,
      citation, and impact factor data, especially for heavily used, highly cited, or
      high-impact-factor journals. The correlations between frequency of use and
      citation frequency and between frequency of use and impact factor were determined
      by using the Spearman rank and Pearson correlation tests. The same comparisons
      were also made within four subject categories: clinical medicine journals, life
      science journals, hybrid journals publishing both clinical medicine and life
      science papers, and journals that publish neither clinical medicine nor life
      science articles. The results of the study showed that there is a significant
      correlation between frequency of use and citation frequency, and between
      frequency of use and impact factor for all titles. There is also a significant
      correlation between frequency of use and citation frequency and between frequency
      of use and impact factor for journals that publish either clinical medicine or
      life science articles, or both. However, the correlation is not significant for
      other journals.

PMID- 9549011
TI  - Who needs evidence-based health care?
AB  - The vast amount of published material in clinical and biomedical sciences, and
      conflicting results on diagnostic and therapeutic procedures may introduce doubts
      in decision-making for patient care. Information retrieving skills and the
      critical appraisal of published literature, together with elaboration of practice
      guidelines based on epidemiological methodology, form the basis of the trend
      towards evidence-based health care, which aims to overcome these problems. A
      survey conducted by questionnaire at the Chaim Sheba Medical Center analyzed
      which types of information sources are considered most relevant and useful for
      patient care by a cross-section of physicians with varying degrees of experience.
      They considered review articles and meta-analyses extremely reliable for
      information purposes, while for practical patient-care purposes they tended to
      rely more on the opinions of peers and experts. As the requirements of evidence
      based health care may influence the attitudes of clinicians to the published
      literature and its evaluation, they have implications for medical libraries and
      information centers. Specifically, information specialists will be called upon
      more and more to impart information-retrieval and critical appraisal skills to
      clinicians. The involvement of information specialists in information gathering
      and selection will provide added value to the expertise and knowledge of in-house
      experts for decision-making.

PMID- 9549012
TI  - Health sciences library building projects, 1996-1997 survey.
AB  - Nine building projects are briefly described, including four new libraries, two
      renovations, and three combined renovations and additions. The libraries range in
      size from 657 square feet to 136,832 square feet, with seating varying from 14 to
      635. Three hospital libraries and four academic health sciences libraries are
      described in more detail. In each case an important consideration was the
      provision for computer access. Two of the libraries expanded their space for
      historical collections. Three of the libraries added mobile shelving as a way of
      storing print materials while providing space for other activities.

PMID- 9549013
TI  - A study of hospital and medical libraries in Riyadh, Kingdom of Saudi Arabia.
AB  - The study reported examined the status of hospital libraries, their sponsoring
      organizations, their staff, the academic qualifications of the head of the
      library, collection size, available space, buildings, and services. The study was
      limited to the hospitals with libraries for staff in Riyadh, the capital of Saudi
      Arabia. The data were collected through questionnaires sent to a sample of
      fifteen hospitals with medical libraries. Twelve libraries responded. This is the
      first study of its kind in Saudi Arabia, and it is hoped that similar surveys
      will be done covering the whole kingdom.

PMID- 9549014
TI  - Complementary use of the SciSearch database for improved biomedical information
      searching.
AB  - The use of at least two complementary online biomedical databases is generally
      considered critical for biomedical scientists seeking to keep fully abreast of
      recent research developments as well as to retrieve the highest number of
      relevant citations possible. Although the National Library of Medicine's MEDLINE
      is usually the database of choice, this paper illustrates the benefits of using
      another database, the Institute for Scientific Information's SciSearch, when
      conducting a biomedical information search. When a simple query about red wine
      consumption and coronary artery disease was posed simultaneously in both MEDLINE
      and SciSearch, a greater number of relevant citations were retrieved through
      SciSearch. This paper also provides suggestions for carrying out a comprehensive
      biomedical literature search in a rapid and efficient manner by using SciSearch
      in conjunction with MEDLINE.

PMID- 9549016
TI  - Hospital library service and the changes in national standards.
AB  - Two important sets of standards affecting hospital libraries were significantly
      revised in 1994, those of the Medical Library Association (MLA) and the Joint
      Commission on Accreditation of Healthcare Organizations (JCAHO). As part of its
      continuing efforts to monitor library services within its region, the University
      of California, Los Angeles Biomedical Library, Regional Medical Library for the
      Pacific Southwest Region of the National Network of Libraries of Medicine (NN/LM)
      conducted a survey in late 1994, in part to determine the effects of these
      revised standards on regional hospital libraries. Data from the survey were also
      used to provide a view of hospital libraries in the Pacific Southwest region, and
      to make comparisons with similar data collected in 1989. Results showed that
      while libraries remained stable in overall number, size, and staffing, services,
      especially those associated with end-user searching and interlibrary loan,
      increased enormously. With respect to the MLA standards, results show a high
      compliance level. Interesting differences were seen between the perceptions of
      library staff concerning their rate of compliance with the JCAHO standards and
      their actual compliance as measured by the MLA criteria. While some libraries
      appear to measure up better than their own perceptions would indicate, others may
      be fully aware of their actual compliance level.

PMID- 9549015
TI  - Scientific meeting abstracts: significance, access, and trends.
AB  - Abstracts of scientific papers and posters that are presented at annual
      scientific meetings of professional societies are part of the broader category of
      conference literature. They are an important avenue for the dissemination of
      current data. While timely and succinct, these abstracts present problems such as
      an abbreviated peer review and incomplete bibliographic access. METHODS: Seventy
      societies of health sciences professionals were surveyed about the publication of
      abstracts from their annual meetings. Nineteen frequently cited journals also
      were contacted about their policies on the citation of meeting abstracts. Ten
      databases were searched for the presence of meetings abstracts. RESULTS: Ninety
      percent of the seventy societies publish their abstracts, with nearly half
      appearing in the society's journal. Seventy-seven percent of the societies supply
      meeting attendees with a copy of each abstract, and 43% make their abstracts
      available in an electronic format. Most of the journals surveyed allow meeting
      abstracts to be cited. Bibliographic access to these abstracts does not appear to
      be widespread. CONCLUSIONS: Meeting abstracts play an important role in the
      dissemination of scientific knowledge. Bibliographic access to meeting abstracts
      is very limited. The trend toward making meeting abstracts available via the
      Internet has the potential to give a broader audience access to the information
      they contain.

PMID- 9549017
TI  - The medical librarian as chief information officer.
AB  - The position of chief information officer (CIO) is gaining popularity, especially
      in the health care field. The results of an informal electronic and telephone
      survey indicate that few medical librarians have made a career move to CIO even
      though this might seem like a logical step. This paper examines the qualities
      required of an effective information management executive, the role CIOs play
      within organizations, and the career advancement strategies for librarians
      interested in becoming CIOs. Questionnaire responses are reported from three
      medical librarians who have made the transition to CIO-type positions, and a case
      study illustrates the responsibilities of CIOs in health care organizations.

PMID- 9549019
TI  - Rehabilitation is always given a low priority.

PMID- 9549018
TI  - Information on alternative medicine: a collection management issue.
AB  - Collection management of library materials about alternative medicine may be a
      growing problem for librarians because differing views exist regarding the
      acceptability of this information in a public forum. The purpose of the study
      reported was to investigate possible differences in the views of physicians,
      medical students, and librarians regarding the availability of information about
      alternative medicine for both medical students and the general public. Interviews
      were conducted with two representatives from each group, all of whom are
      affiliated with the Faculty of Medicine at The University of British Columbia or
      its library. The study was exploratory in nature, conducted in part to determine
      whether a larger research project in this area should be mounted. The data
      revealed considerable differences in opinion about alternative medicine: the
      librarians were more hesitant about the acceptability of radical or revolutionary
      materials, particularly those containing information that could result in direct
      harm to a patient. The physicians and medical students were more confident than
      the librarians that traditional medical treatment (and therefore information
      about it) should always be paramount.

PMID- 9549020
TI  - Respect for autonomy: issues in neurological rehabilitation.
AB  - OBJECTIVE: To examine the ethical principle of respect for autonomy within the
      context of neurological rehabilitation. DISCUSSION: The nature of the principle
      of respect for autonomy is examined, and specific difficulties to which it may
      give rise in this area of practice are identified. These concern difficulties of
      communication with neurologically impaired patients, issues of competence related
      to patient decision-making, problems of consensus between patient and
      professional, and the role of the patient's family in the rehabilitation process.
      CONCLUSION: A number of strategies, based on a client-centred model of practice,
      are suggested which may counteract these difficulties and assist in respecting
      the patient's autonomy to the appropriate degree, while seeking to attain high
      quality clinical outcomes.

PMID- 9549021
TI  - Electromyographic biofeedback for gait training after stroke.
AB  - OBJECTIVE: To examine the effects of electromyographic (EMG) biofeedback training
      on the recovery of gait in the acute phase post stroke. DESIGN: Patients were
      randomly assigned to EMG biofeedback or control groups. They received treatment
      three times a week for six weeks. All patients were assessed prior to treatment,
      after 18 treatment sessions, and at three months follow-up. SETTING: The study
      was carried out at Scunthorpe General Hospital in North Lincolnshire. The
      subjects were acute stroke patients who had been admitted on to the medical and
      elderly wards. INTERVENTIONS: The EMG biofeedback group were treated using EMG as
      an adjunct to physiotherapy. The patients were encouraged to facilitate or
      inhibit abnormal muscle tone via auditory or visual signals transmitted from
      electrodes placed over the appropriate muscles. The control group were treated
      using the same techniques, electrodes were used with this group of patients, but
      the EMG machine was turned off and faced away from the patient and the therapist
      to control the placebo effect. OUTCOME MEASURES: A large battery of outcome
      measures was used for physical and psychological assessment. The physical
      measures consisted of active movement, muscle tone, sensation, proprioception,
      mobility and activities of daily living (ADL). The psychological measures
      included orientation, memory, spatial performance, language and IQ. RESULTS:
      Twenty-one patients were included in the study. Scores were combined into four
      groups: mild EMG, severe EMG, mild control and severe control. Results showed
      that there was an improvement in physical scores for active movement, mobility
      and ADL over time, but there was no significant difference between the EMG and
      control groups. Scores on the psychological tests were within normal limits, and
      there was no difference in performance between the EMG and control groups.
      CONCLUSIONS: This study showed no significant differences in the rate of
      improvement after stroke between the two groups. Although EMG biofeedback was
      used as an adjunct to physiotherapy and represented clinical practice, the
      results provide little evidence to support the clinical significance of using EMG
      biofeedback to improve gait in the acute phase after stroke.

PMID- 9549023
TI  - Ten-metre walk, with or without a turn?
AB  - OBJECTIVE: To compare results obtained using different procedures to measure 10
      metre walking time. DESIGN: Walking was timed over a straight 10 m, and over 5 m
      with return. Further, the time taken to turn was measured directly. SETTING:
      Rehabilitation department of a university hospital. SUBJECTS: Patients who had
      walking disability after stroke. RESULTS: In the group of 43 patients, the time
      taken to walk 5 m and return was 3.3 (SD 5.0)s longer than the time to walk 10 m
      straight, but there was a large variation with some patients walking faster. The
      measured time to turn in a second group of 27 patients was 3.2 (SD 1.6)s. The
      times taken to walk 10 m straight and 5 m and return, and the time taken to turn
      were all highly correlated (r = 0.69 or more). CONCLUSIONS: Timing walking over 5
      m with a return is an acceptable alternative to the 10 m straight walk, but the
      actual time taken varies. On average, the walk with a turn is 3.2 s longer but in
      individual patients the difference may be much more or less. Sometimes the walk
      with a turn is even faster than that without.

PMID- 9549022
TI  - The treatment of lateral epicondylitis by iontophoresis of sodium salicylate and
      sodium diclofenac.
AB  - OBJECTIVE: To investigate the effectiveness of sodium diclofenac and sodium
      salicylate applied by topical iontophoresis and to compare them in the treatment
      of lateral epicondylitis. SUBJECTS: Forty patients with lateral epicondylitis
      were randomized into two groups of 20 patients who were matched for age and sex.
      INTERVENTIONS: The patients in one group were treated by iontophoresis of sodium
      diclofenac and the other group were treated by iontophoresis of sodium
      salicylate. Then infrared treatment was applied to patients in both groups. MAIN
      OUTCOME MEASURES: Pain scores obtained before and after treatment were compared.
      RESULTS: Pain produced by pressure on the lateral epicondyle, on resisting wrist
      extension, during function and spontaneous pain at rest significantly decreased
      in both groups after treatment (p < 0.001). When pain scores obtained after
      treatment were compared, greater decrease was observed in the pain produced on
      resisting wrist extension (p < 0.01) and by pressure on the lateral epicondyle (p
      < 0.05) in the group treated with sodium diclofenac than in the group treated
      with sodium salicylate. CONCLUSIONS: The results suggest some benefits from the
      process of iontophoresis and the use of infrared in the treatment of lateral
      epicondylitis and indicate that iontophoresis of sodium diclofenac is more
      effective than that of sodium salicylate.

PMID- 9549024
TI  - Neck semispinalis capitis muscle size in sitting and prone positions measured by
      real-time ultrasonography.
AB  - OBJECTIVE: To examine the reliability of measurements of semispinalis capitis
      muscle (SECM) cross-sectional area (CSA) in prone and sitting positions, and to
      compare the muscle size in these two positions. DESIGN: Semispinalis capitis CSA
      was measured twice a day on two successive days with a real-time ultrasound
      apparatus. SUBJECTS: Eighteen males (aged 19-34 years) and 28 females (aged 19-34
      years) were studied for the reliability test. Seven males and 12 females were
      randomly selected to compare SECM size in sitting and prone positions. RESULTS:
      The intraclass correlation coefficient (ICC) for repeatability measurements was r
      = 0.98 for the two positions. The correlation of the CSA in sitting and in prone
      positions was r = 0.93 (p < 0.01). There were no significant differences between
      CSA, linear dimensions and shape ratio of SECM in the two positions. CONCLUSIONS:
      In this study SECM ultrasonography appeared to be an accurate method in both
      positions, and position as such had no significant effects on the SECM cross
      sectional size. Such accuracy allows neck muscle evaluation in clinical diagnosis
      and in follow-up studies during neck rehabilitation programmes.

PMID- 9549025
TI  - What do patients and their carers want to know about stroke? A two-year follow-up
      study.
AB  - OBJECTIVE: To clarify what issues are important to stroke patients and their
      carers. To determine whether these issues change over time. DESIGN: Prospective
      study of consecutive patients admitted to hospital with a diagnosis of an acute
      stroke. Each participant had interviews at six and 24 months. In addition, a
      subgroup of these patients (consecutive discharges over a two-month period) were
      also seen at two weeks post discharge. SETTING AND SUBJECTS: Hospital-based
      cohort of stroke survivors. Interviewed in their own homes. MAIN OUTCOMES
      MEASURES: Documentation of the questions asked. RESULTS: At two weeks, six and 24
      months, a median of three, two and three questions were asked by each patient
      respectively. Enquiries about basic aspects of stroke were common but diminished
      over time. Fear of recurrence was apparent at all three interview periods.
      Enquiries about the psychological sequelae of stroke became more prevalent at six
      and 24 months. At two years, 32% of respondents asked about concentration/memory
      difficulties with smaller numbers commenting on tiredness, depression and
      frustration. At two years, 18% of the sample were still uncertain of their
      chances of further recovery. CONCLUSIONS: Patients with stroke continue to have
      unanswered questions even two years after their stroke. The types of questions
      asked changed over time.

PMID- 9549026
TI  - Assault, post-traumatic amnesia and other variables related to outcome following
      head injury.
AB  - OBJECTIVE: To estimate how many patients who sustain a head injury might benefit
      from intervention and support each year and to consider whether relationships can
      be found between demographic data relating to patients' circumstances at the time
      of head injury, and their outcomes six months later. DESIGN: Data collected on
      625 patients through follow-up interviews and assessments by the Oxford Head
      Injury Service for a randomized controlled trial of intervention conducted in
      1993-94. SETTING: A mixed rural and urban Health District with a population of
      approximately 560,000. PATIENTS: Patients were aged between 16 and 65 years and
      resident in Oxfordshire. They presented over 13 months to accident and emergency
      departments, or were admitted to hospital. All were diagnosed as having suffered
      a head injury. OUTCOME MEASURES: The Rivermead Head Injury Follow Up
      Questionnaire and the Rivermead Post Concussion Symptoms Questionnaire. RESULTS:
      Data are given on age, sex, social circumstances, employment, cause of injury,
      severity of associated injuries, post-traumatic amnesia (PTA), anticonvulsants,
      postconcussion symptoms and activities of everyday life. Outcome at six months
      was significantly worse for those who had been assaulted as against all other
      causes of injury combined (p = 0.0001); and/or had been admitted to hospital (p =
      0.0001)l and/or had sustained more severe additional injuries (p = 0.04); and/or
      had experienced any PTA (p = 0.00001). The minimum incidence of such injuries in
      those aged 16-65, calculated for Oxfordshire, is 292 per annum (74/100,000 aged
      16-65 per year). CONCLUSIONS: In the general population 52/100,000 patients per
      annum will experience more serious head injuries as indicated by hospital
      admission and/or one or more fractures and/or any length of PTA and/or having
      been assaulted. This group may benefit from monitoring and support and their
      needs should be considered when planning services.

PMID- 9549027
TI  - Manual dexterity and keyboard use in spastic hemiparesis: a comparison between
      the impaired hand and the 'good' hand on a number of performance measures.
AB  - OBJECTIVE: To assess the functional deficits in tapping performance of subjects
      with spastic hemiparesis. DESIGN: In a pilot study, typing performance on a
      computer keyboard was examined on a number of performance measures. SETTING:
      Department of Research and Development at the Werkenrode Institute. SUBJECTS:
      Four subjects (mean age 16.4 years, standard deviation 1.8 years) with cerebral
      palsy and diagnosed as having spastic hemiparesis. INTERVENTIONS: Subjects had to
      type a sequence of one or more keys as quickly as possible within an 8 second
      period with the fingers of both hands separately. MAIN OUTCOME MEASURES: The
      average number of good and false responses were calculated. Within the false
      response category, four, mutually exclusive, types of errors were distinguished;
      wrong key, repetition, registrations under 75 ms and holding. Speed and
      regularity of the typing responses were also established. RESULTS: The 'good'
      hand outperformed the impaired hand on all performance measures except on the
      amount of repetition errors made. The holding error was only present for the
      impaired hand, and there was an increase in holding errors from the index to the
      little finger in this hand. In addition, the impaired hand performed the task
      with a slower speed and in a more irregular fashion. CONCLUSIONS: The results are
      discussed with reference to keyboard design. It is concluded that the standard
      'QWERTY' keyboard hampers typing performance extensively, especially for subjects
      with left spastic hemiparesis. A learning method is presented in which the role
      of an external pacer (e.g. metronome) is discussed. This device can initially be
      used to decrease movement variability and, eventually, for increasing movement
      speed.

PMID- 9549028
TI  - The effects of depression and abnormal illness behaviour on outcome following
      rehabilitation from stroke.
AB  - OBJECTIVE: To examine the relative effects of depression and abnormal illness
      behaviour (AIB) on long-term rehabilitation outcome following stroke. DESIGN: A
      longitudinal design, with assessments on admission to and discharge from
      rehabilitation, and six and twelve months after discharge. SETTING: The study was
      undertaken in the rehabilitation unit at Repatriation General Hospital, in
      Adelaide, South Australia. SUBJECTS: Ninety-four twelve-month stroke survivors
      who had undergone an inpatient rehabilitation programme. MAIN OUTCOME MEASURES:
      AIB was assessed using the Illness Behaviour Questionnaire, and depression with
      the Zung Self-Rating Depression Scale. The General Health Questionnaire and a
      visual analogue mood scale were also used. Functional outcome was assessed with
      the competence and performance assessments of the Australian ADL Index, and
      lifestyle activities with the Frenchay Activities Index. RESULTS: Multivariate
      analysis of outcome controlled for age and stroke severity. AIB was a better
      predictor of functional competence and performance than either age or stroke
      severity, at rehabilitation discharge and both six and twelve months later.
      Depression was not related to functional competence and performance at any
      assessment, but was strongly predictive of an inactive lifestyle at both six and
      twelve months. By contrast, lifestyle activities were not related to AIB.
      CONCLUSIONS: Depression and AIB appear to have quite distinct effects on outcome.
      AIB emerged as a key determinant of long-term functional disability, while
      depression was associated with poorer social functioning. The early recognition
      and treatment of AIB and depression is important for the ultimate social and
      functional outcomes of stroke rehabilitation patients.

PMID- 9549029
TI  - The use of self-management strategies by people with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate seven common arthritis self-management methods used by
      people with rheumatoid arthritis (RA) by studying their frequency of use and the
      patients' belief in their benefits. Also to look at how people obtained
      information about such methods. DESIGN: Cross-sectional survey. SUBJECTS AND
      SETTING: Forty-one people with RA attending a rheumatology outpatient department
      at a large district general hospital. RESULTS: Twenty-three recalled receiving
      some self-management advice from rheumatology team members, but most stated the
      commonest source of information was arthritis books and leaflets (n = 29). Two
      thirds used technical aids and rest on a daily basis, half used exercise and heat
      (half doing so daily). A quarter to a half used relaxation, joint protection and
      working splints (half doing so daily). CONCLUSION: People with RA reported using
      three or four self-management methods simultaneously to help control symptoms. In
      the main, believing a method to be beneficial was strongly related to its use.
      However, exercise and joint protection, whilst widely believed to be beneficial,
      were less used. People reported problems with knowing how to do these correctly,
      having insufficient time to practise sufficiently and difficulty in establishing
      habits.

PMID- 9549030
TI  - Environmental control systems--an audit of existing provision in three inner
      London districts.
AB  - OBJECTIVE: To undertake an audit of existing environmental control system (ECS)
      provision to see what lessons could be applied to developing a new model of
      service. DESIGN: Structured interviews and assessments making use of
      questionnaires and algorithms. SUBJECTS: Users of environmental control systems
      in the inner London boroughs of Lambeth, Southwark and Lewisham (population
      720,000) supplied with equipment prior to April 1996 out of National Health
      Service funds. SETTING: All users were assessed and interviewed in their own
      homes. RESULTS: In all, 29 users of ECSs were surveyed. Six users were found to
      have systems either so outdated or poorly planned as to be nearly useless. Seven
      users were felt not to justify an ECS and many systems were felt to be over
      specified, leading to wastage of equipment. Many medical and nonmedical needs,
      not directly related to the users' ECSs, were identified. CONCLUSIONS: While the
      recommendations of the British Society of Rehabilitation Medicine special
      interest group on ECS are welcomed, it is thought that these do not go far
      enough. In particular the role of the environmental control assessor needs to
      extend to participation in the case conference where the exact equipment
      requirements of the prescribed ECS is agreed, and thereafter to include
      responsibility for ensuring regular review of users. In such a model of service
      the current single payment for a one-off assessment is felt to be inappropriate.

PMID- 9549031
TI  - Reproductive hormones and gastrointestinal motor disorders: a new dimension in
      therapeutics.

PMID- 9549032
TI  - Relationship of reproductive hormones and neuromuscular disease of the
      gastrointestinal tract.
AB  - Functional disorders of the gastrointestinal tract comprise a common but ill
      defined group of diseases; they primarily afflict women. Although predominantly
      involving nerve and muscle, the cellular and molecular bases of the pathogenesis
      of these functional disorders are unknown. Clinical studies indicate that some
      result from neural dysfunction within the enteric nervous system, others may be
      due to muscular problems, and the causes of still others remain unknown.
      Laboratory studies have shown that ovarian products such as progesterone,
      luteinizing hormone, human chorionic gonadotropin, and relaxin (but not
      estrogen), are neural antagonists of gastrointestinal motility. The production
      and secretion of these ovarian substances are controlled by gonadotropin
      releasing hormone (GnRH) released from the hypothalamus; they probably act on
      gamma-aminobutyric acid receptors and alter chloride influx into the cell. GnRH
      analogs are effective drugs that downmodulate the hypothalamic-pituitary-gonadal
      axis and inhibit the secretion of gonadal products involved in such hormone
      dependent diseases as endometriosis and prostate cancer. Acting on the GnRH
      receptors (seven transmembrane domain receptors) on myenteric neurons, GnRH
      analogs are also effective neural modulators in such disorders as functional
      bowel disease. These analogs are a promising new group of compounds that may be
      used to treat difficult gastrointestinal problems.

PMID- 9549033
TI  - Use of botulinum toxin in the treatment of achalasia.
AB  - Achalasia is a chronic esophageal motor disorder characterized by failure of the
      lower esophageal sphincter (LES) to relax during swallowing, aperistalsis of the
      esophageal body, and, often, an elevated resting LES pressure. Pneumatic dilation
      and Heller cardiomyotomy have been the time-honored, accepted treatments, but
      each may carry significant morbidity. Recently, intrasphincteric injection of
      botulinum toxin has been shown to be an effective treatment for achalasia,
      probably by reducing the excitatory cholinergic tone of the LES. Subjective and
      objective improvement have been reported in many patients with few reported
      adverse reactions. Clinical improvement generally lasts 2-6 months with patients
      often requiring repeat treatment. Although studies directly comparing botulinum
      toxin injection with pneumatic dilation and surgical myotomy are needed,
      botulinum toxin injection has rapidly become another therapeutic option in the
      treatment of achalasia.

PMID- 9549034
TI  - Gene therapy for liver disease.
AB  - With major advances in biomedical science over the last 2 decades, the
      possibility of treating human disease at a genetic level has become a tantalizing
      possibility. As a result, a growing number of investigators are focusing on the
      development of techniques to deliver therapeutic genes into cells. The liver has
      been a model organ in the development of this gene transfer technology. This
      review focuses on the attributes and limitations of the current gene delivery
      systems that have been explored in the context of liver disease and highlights
      the obstacles that must be addressed before hepatic gene therapy becomes a
      clinical reality.

PMID- 9549035
TI  - A prokinetic approach to treatment of gastroesophageal reflux disease.
AB  - Currently available medications for gastroesophageal reflux disease (GERD) vary
      in mechanisms of action from neutralization or suppression of gastric acid to
      improving underlying upper gastrointestinal dysmotility. This article reviews the
      clinical efficacy of pharmacological agents used to treat GERD and provides a
      rationale for considering a primary prokinetic approach to antireflux treatment
      which will be applicable to many patients. Treatment trials in acute GERD have
      demonstrated unexpectedly prolonged maintenance of high esophageal pH with tablet
      and liquid antacid formulations. However, there are no well-designed placebo
      controlled trials of antacids for esophageal mucosal healing. H2 receptor
      antagonists (H2RAs) at conventional doses relieve reflux symptoms in at least 50%
      of reported series of GERD patients, and they can also provide endoscopic healing
      in 27-45% of the cases. Therapy with more potent acid-suppressive agents such as
      proton pump inhibitors (PPIs) may lead to improved symptomatic relief and to
      superior healing compared with H2RA therapy, especially in those patients with
      more advanced erosive esophagitis. Promotility agents, particularly cisapride,
      offer symptom relief and healing rates which are quite similar to standard H2RA
      treatment. GERD tends to be a chronic and relapsing condition. Cisapride has been
      shown to be quite effective in maintaining remission in GERD patients, including
      endoscopic remission in the lesser degrees of esophagitis. This may be
      accomplished with relatively low and cost-effective dosing in many individuals.
      For the small proportion of patients who manifest severe grades of esophagitis,
      PPI therapy is associated with lower relapse rates than either H2RA or prokinetic
      treatment. Overall, a strong case can be made for the empirical selection of
      promotility therapy for the large numbers of GERD patients who do not have
      documented severe erosive disease.

PMID- 9549036
TI  - Antimicrobial treatment of intra-abdominal infections.
AB  - There have been several recent changes that influence the management of intra
      abdominal infections. These changes include important developments in antibiotic
      resistance such as increases in pneumococcal resistance, emergence of multi-drug
      resistant enterococcal isolates, and decreasing sensitivity of anaerobes and gram
      negative rods. In addition there are new antibiotics such as
      piperacillin/tazobactam, and new antibiotic dosing regimens such as single daily
      dosing of aminoglycosides. In this article, we will review the therapeutic
      approach to intra-abdominal infections with special emphasis on the various forms
      of peritonitis, cholecystitis, cholangitis, and diverticulitis. Several new
      concepts about the treatment of enterococcus, the management of bacterial and
      fungal peritonitis, and the prevention of spontaneous bacterial peritonitis will
      also be reviewed. Specific recommendations for the management of the different
      infections including antibiotic doses and costs will be provided. Finally the
      role of invasive procedures in the management of some of the infections will be
      explored.

PMID- 9549037
TI  - Esophageal carcinoma with obstruction.

PMID- 9549040
TI  - Synergistic insulinotropic action of succinate, acetate, and glucose esters in
      islets from normal and diabetic rats.
AB  - Succinic acid esters are currently under investigation as possible insulinotropic
      tools in the treatment of noninsulin-dependent diabetes mellitus. The present
      article introduces three novel nutrient esters and aims mainly to explore, in
      both normal and GK rats, the secretory response to such esters when tested alone
      or in combination. It documents that in pancreatic islets from normal rats,
      methyl acetate (10 mM), which fails to augment basal insulin output, potentiates
      the secretory response to succinate dimethyl ester (also 10 mM). It also reveals
      that alpha-D-glucose pentaacetate (alpha GPA) (1.7 mM) stimulates insulin release
      in the absence of any other exogenous nutrient and even more so in the presence
      of succinate methyl ester. Moreover, the methyl esters of succinic acid (10 mM),
      when used together with either methyl acetate or alpha GPA, provoked insulin
      secretion in islets from diabetic GK rats incubated in the absence of D-glucose,
      although no significant secretory response of such islets could be detected when
      each of these agents was tested separately. These findings thus draw attention to
      the insulinotropic potential in type 2 diabetes of selected combinations of
      nutrient esters, including a D-glucose ester presumably able to enter into islet
      cells without requiring the intervention of a hexose carrier.

PMID- 9549039
TI  - Leptin, corticotropin-releasing hormone (CRH), and neuropeptide Y (NPY)in free
      ranging pregnant bats.
AB  - Leptin, the product of the obese gene first identified in mice, restores
      fertility in obese mice, and accelerates puberty in mice. We hypothesized that
      leptin's putative role in reproduction may extend to pregnancy and lactation.
      Leptin levels were determined in Myotis lucifugus, the little brown bat, a free
      ranging mammal with a seasonal breeding cycle. The present study shows that
      plasma levels of leptin progressively rise during pregnancy, supporting a
      potential role for leptin in the maintenancy of pregnancy. In contrast, leptin
      was significantly lower during lactation, a time when most mammals, including
      bats, demonstrate reduced fertility. In addition to its possible roles in
      reproduction, leptin appears important in regulation of energy balance. M.
      lucifugus spontaneously fasts for up to 16 h each day during the active season,
      which allowed us to test the hypothesis that acute fasting was associated with
      decreased leptin. Leptin was significantly lower in fasted (lactating) bats,
      compared to those that recently returned from nightly foraging. Although
      postprandial lactating bats had a significantly higher fat index than fasted
      bats, plasma leptin and body fat were not significantly correlated, and were only
      weakly correlated (r2 = 0.26) when both pregnant and lactating females were
      included in the analysis. Similar changes during pregnancy, lactation, and the
      daily feeding cycle were observed in the hypothalamic neuropeptide, corticotropin
      releasing hormone (CRH), which is believed to play an important role in energy
      balance and reproduction. By contrast, neuropeptide Y (NPY) increased during
      pregnancy but did not change during fasting. These results suggest that leptin's
      putative role in reproduction may extend to pregnancy and lactation, and that
      spontaneous, acute fasting results in decreased circulating levels of leptin in
      M. lucifugus.

PMID- 9549041
TI  - Effects of GH on IGF-II-induced progesterone accumulation by cultured porcine
      granulosa cells.
AB  - A total of seven experiments were conducted to investigate the potential
      facilitative interaction of growth hormone (GH) and insulin-like growth factor II
      (IGF-II) in stimulating steroidogenesis by cultured porcine granulosa cells and
      to examine the possible nature of this action. Porcine granulosa cells were
      cultured in serum-free medium in the presence or absence of GH or prolactin, with
      or without IGF-II or IGF-I. IGF-II by itself dose (with peak progesterone
      production of 498 ng/mg DNA/24 h being observed at 100 ng of IGF-II/mL) and time-
      (with minimum time requirement of 24-48 h) dependently increased progesterone
      accumulation (P < 0.01). Neither GH (dose range 0, 5, 10, 50, 100, and 150 ng/mL)
      nor prolactin (dose range 0, 0.01, 0.1, 1, 5, 10 micrograms/mL) alone stimulated
      progesterone accumulation when compared with the control (P > 0.05). However, in
      the presence of IGF-II, GH proved to be a potent amplifier of IGF-II in
      progesterone production (P < 0.01) with a minimum GH time requirement of 24-48 h.
      In contrast, prolactin did not influence IGF-II-induced progesterone accumulation
      (P > 0.05). An inhibitory study showed that the presence of cycloheximide (3
      micrograms/mL) or actinomycin D (1 microgram/mL) blocked both the stimulatory
      effect of IGF-II on progesterone accumulation and the amplification of GH on IGF
      II induced production (P > 0.01), suggesting GH amplification of IGF-II-induced
      progesterone accumulation is a process involving gene transcription and
      translation. Northern blot analysis further demonstrated that GH amplification of
      IGF-II-induced steroidogenesis can be attributed, at least partially, to enhanced
      IGF-II-induced cytochrome P450 cholesterol side-chain cleavage mRNA by GH.

PMID- 9549043
TI  - Dopamine D2 receptor mediates both inhibitory and stimulatory actions on
      prolactin release.
AB  - Dopamine is considered to be the major physiological tonic inhibitor of prolactin
      release, yet there is increasing evidence showing that it can also stimulate
      prolactin release from lactotrophs. In primary cultured lactotrophs, the major
      dopamine receptors responsible for inhibiting prolactin release are dopamine D2
      receptors. A dopamine receptor subtype may be responsible for the stimulatory
      action, yet one cannot exclude the possibility that a dopamine D2 receptor can
      play dual roles. This study was therefore undertaken to investigate if dopamine
      both stimulates and inhibits prolactin secretion through activation of the same
      dopamine D2 receptor. GH4ZR7 cells, which have only one type of dopamine
      receptors--D2s, were perifused with different concentrations of dopamine, and the
      perifusate was assayed for prolactin; 10(-7) mol/L dopamine stimulated prolactin
      release (p < 0.05; n = 5), whereas 5 x 10(-4) mol/L dopamine inhibited prolactin
      secretion (p < 0.05; n = 5). In the pertussis toxin-treated cells, 10(-7) mol/L
      dopamine stimulated prolactin release (p < 0.05; n = 5), and 5 x 10(-4) mol/L
      dopamine did not significantly change the rate of prolactin release. These
      results indicate that both the stimulatory and inhibitory actions of dopamine are
      likely mediated by the same D2 receptor subtype, since GH4ZR7 cells express only
      D2s receptors. They also confirm that the inhibitory action of dopamine is
      mediated through a Gi protein; and the stimulatory action of dopamine is mediated
      through a PTX-insensitive pathway. These findings suggest that D2 receptors are
      coupled to both Gi and Gs proteins.

PMID- 9549038
TI  - Is signal transduction modulated by an interaction between heterotrimeric G
      proteins and tubulin?
AB  - Although it is generally accepted that tubulin plays an important role in G
      protein-mediated signal transduction in a variety of systems, the mechanism of
      this phenomenon is not completely understood. G-protein-tubulin interaction at
      the cell membrane and the cytosol, and the influence of such an interaction on
      cellular signaling are discussed in this review article. Because the diameter of
      a microtubule is 25 nm and the plasma membrane is 9-11 nm thick, it is not
      possible for membrane-associated tubulin to assemble into a complete microtubule
      in the membrane environment. However, tubulin heterodimers may be able to
      function in the membrane environment as individual heterodimers or as polymers
      arranged into short protofilaments. At the cell membrane, membrane-associated
      tubulin may influence hormone-receptor interaction, receptor-G-protein coupling,
      and G-protein-effector coupling. Structural proteins, such as tubulin, can
      participate in cellular signaling by communicating through physical forces. By
      virtue of its interaction with the submembranous network of cytoskeletal
      proteins, tubulin, when perturbed in one locus, can transmit large changes in
      conformations to other points. Thus, GTP binding to membrane-associated tubulin
      might lead to a conformational change in either receptors or G proteins. This
      may, in turn, influence the binding of an agonist to its receptor. On the other
      hand, in the cell cytosol, subsequent to agonist-induced translocation of G
      proteins from the membrane compartment to the cytosol, G-proteins may affect
      microtubule formation. In GH3 and AtT-20 cells (stably expressing TRH receptor),
      transiently transfected with Gq alpha cDNA, soluble tubulin levels decreased in
      Gq alpha-transfected GH3 and AtT-20 cells, by 33% and 52%, respectively. These
      results suggest that G-proteins may have a direct effect on the microtubule
      function in vivo. Because tubulin and G-protein families are ubiquitous and
      highly conserved, an interaction between these two protein families may occur in
      vivo, and this, in turn, can have an impact on signal transduction. However, the
      physiological significance of this interaction remains to be demonstrated.

PMID- 9549042
TI  - Decreased osteoblast activity in spontaneously diabetic rats. In vivo studies on
      the pathogenesis.
AB  - Diabetes in both humans and rats is accompanied by low bone formation, which is
      presumably caused by serum-borne factors. To explore its pathogenesis, we carried
      out experiments in diabetic and nondiabetic BB rats, using plasma osteocalcin
      concentrations (OC) as a marker for osteoblast activity. In nondiabetic rats, the
      i.v. infusion of glucose (30%, 4 d) did not change OC; s.c. insulin infusion (4
      U/d, 14 d) reduced OC by 27% (p < 0.01). In diabetic rats, OC were decreased from
      the first day of glycosuria (71 +/- 5% of paired controls), declining
      exponentially to 24 +/- 3% after 5 wk. Insulin infusion (1, 2, and 3 U/d, 14 d)
      produced gradual restoration of OC. OC were better correlated with insulin-like
      growth factor-I (IGF-I) than with insulin levels in these experiments. OC were
      dramatically increased 4 d after adrenalectomy (ADX) in all diabetic rats (73 +/-
      8 vs 22 +/- 4 micrograms/L before ADX; p < 0.001), but not if corticosterone was
      administered. Ligand blotting of IGF binding proteins showed a marked decrease in
      two bands (44-49 and 32-35 kDa) 10-14 d after diabetes onset; the density of
      these bands was increased, but not normalized after ADX. Thus, decreased
      osteoblast activity is present from the onset of diabetes, is dependent on
      endogenous corticosterone, and cannot be reproduced by hyperglycemia in
      nondiabetic rats.

PMID- 9549044
TI  - Specific antibody recognition of rat pituitary adenylate cyclase activating
      polypeptide receptors.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the
      secretin/VIP family of peptides. The specific receptor for PACAP has been cloned
      in rat, human, and bovine tissues. The distribution of the transcripts of PACAP
      receptor genes has been studied in various tissues using in situ hybridization.
      However, the unavailability of a specific antibody against the PACAP receptor has
      hampered further study of the expression of receptor proteins. In the present
      study, rabbit antisera were generated against a synthetic 25-residue peptide
      corresponding to the C-terminal intracellular domain of the rat PACAP receptor.
      To validate the specificity of the antisera, CHO cells and cells stably
      transfected with rat PACAP receptor cDNA were prepared. Using one of these
      antisera, the membrane and soluble fractions of the transformants were examined
      by Western blot analysis. Three bands were observed in subcellular fractions from
      the transfected CHO cells, but no bands were found in similar preparations from
      the nontransfected cells. A distinct 57-kDa band, which corresponds to the size
      of cloned rat PACAP receptor, was detected. In addition, a less intense band,
      larger than 57 kDa, and a very weakly stained band, smaller than 57 kDa, were
      demonstrated. All of these bands disappeared or were considerably diminished when
      the antiserum was preabsorbed with the synthetic immunogen peptide. This suggests
      that these bands are PACAP receptor-related proteins. The membranes from the
      transfected CHO cells bound to [125I]PACAP27. The size of the ligand/protein
      crosslinked product approximated 60 kDa, corresponding to the combined size of
      the PACAP receptor and PACAP27. No additional bands were observed, indicating
      that the immunopositive proteins larger or smaller than 57 kDa do not bind to the
      ligand and are not functional. Unlabeled PACAP27 and PACAP38, but not VIP,
      displaced the binding, suggesting that the receptors expressed in CHO cells are
      specific for PACAP. Solubilized membrane fractions prepared from rat brains were
      used for an immunoprecipitation study with [125I]PACAP27 and [125I]VIP. The PACAP
      receptor antiserum recognized [125I]PACAP-, but not [125I]VIP-bound proteins in
      the solubilized brain membrane fractions. Immunohistochemistry using this
      antiserum showed a distribution of PACAP receptor-like immunoreactivities similar
      to the distribution of the mRNA of PACAP receptor in the rat brain. Thus, the
      PACAP receptor antiserum is sufficiently specific to be used as a tool for
      studying the expression of PACAP receptors and related proteins.

PMID- 9549045
TI  - Uterine estrogen sulfatase may play a more important role than the hepatic
      sulfatase in mediating the uterotropic action of estrone-3-sulfate.
AB  - The estrogenic activity of sulfonated estrogens results from the release of
      active estrogens via desulfonation (hydrolysis) catalyzed by estrogen sulfatase.
      In this study, the relative importance of uterine or hepatic estrone (E1)-3
      sulfatase in mediating the uterotropic action of E1-3-sulfate is evaluated by
      comparing its hormonal potency in animals that have comparable uterine E1-3
      sulfatase activity but markedly different hepatic enzyme activity. Liver
      microsomes from immature or adult female Sprague-Dawley rats contained 12- or 55
      fold higher E1-3-sulfatase activity, respectively, than the liver microsomes from
      immature or adult female CD-1 mice. In contrast, uterine whole homogenates from
      immature female Sprague-Dawley rats contained approx twofold higher E1-3
      sulfatase activity than was detected in the uterine whole homogenates from
      immature female CD-1 mice. It is estimated that the total E1-3-sulfatase activity
      in the liver of an immature female rat or mouse is approx 1080- or 260-fold
      higher, respectively, than the activity in the uterus. The ED50 values for the
      uterotropic effect of E1-3-sulfate and E1 in immature female CD-1 mice were 240
      and 8 pmol/g body wt, respectively, and the corresponding ED50 values in immature
      female Sprague-Dawley rats were 840 and 60 pmol/g body wt, respectively. The
      difference in the ratios of the uterotropic ED50 for E1-3-sulfate over that for
      E1 in immature rats and mice (14 and 30, respectively) is 1.14-fold, which
      correlates very closely with their difference in the uterine E1-3-sulfatase
      activity (approx twofold), but not their difference in the hepatic sulfatase
      activity (approx 12-fold). The results of this study provide evidence suggesting
      that E1-3-sulfatase in the uterus (an estrogen target organ) may play a more
      important role than the hepatic sulfatase in mediating the uterotropic action of
      sulfonated estrogens.

PMID- 9549046
TI  - Insulin induction of pip 92, CL-6, and novel mRNAs in rat hepatoma cells.
AB  - Insulin directly affects many aspects of cellular metabolism. An additional,
      poorly studied effect of insulin is the regulation of multiple genes whose
      products are important in many cellular functions. Using differential screening
      techniques, we identified insulin-regulated genes induced in insulin-treated rat
      H4IIE (H4) hepatoma cells. Two of the mRNAs identified were homologous to the
      previously characterized mouse pip 92 and rat CL-6 immediate-early genes. The pip
      92 clone was initially isolated from mitogen-stimulated mouse Balb/c 3T3
      fibroblasts, whereas the CL-6 clone was first isolated from regenerating rat
      liver. In this article, we demonstrated that in rat H4 cells, the transcription
      rates of both pip 92 and CL-6 are induced by insulin alone. Additionally, we
      showed that the transcription rates of two other genes, whose sequences are not
      homologous to any other sequences in gene bank ("novel genes"), were rapidly and
      transiently induced by insulin. These results demonstrate that insulin regulates
      the expression of several novel genes with a time-course similar to members of
      the immediate-early response gene family.

PMID- 9549047
TI  - The effects of 17 beta-estradiol on chondrocyte differentiation are modulated by
      vitamin D3 metabolites.
AB  - Both 17 beta-estradiol (17 beta) and the vitamin D metabolites, 1,25
      (OH)2D3(1,25) and 24,25-(OH)2D3(24,25), regulate endochondral bone formation in
      vivo and in vitro. The effects of 17 beta are sex-specific and cell maturation
      dependent. Similarly, the effects of 1,25 and 24,25 are cell maturation
      dependent, with 1,25 affecting growth zone chondrocytes (GC) and 24,25 affecting
      resting zone chondrocytes (RC). This study examined whether the response of
      chondrocytes to 17 beta is altered after pretreatment with 1,25 or 24,25. Cells
      were isolated from the costochondral cartilage of male or female rats. Confluent,
      fourth-passage GC and RC cultures were pretreated with 1,25 or 24,25,
      respectively, for 24 or 48 h followed by treatment with 17 beta for an additional
      24 h. At harvest, cell proliferation ([3H]-thymidine incorporation),
      differentiation (alkaline phosphatase specific activity [ALPase]), general
      metabolism ([3H]-uridine incorporation), and proteoglycan production ([35S]
      sulfate incorporation) were determined. 1,25 enhanced the inhibitory effect of 17
      beta on [3H]-thymidine incorporation by female GC cells; in contrast, no effect
      was observed in GC cells obtained from male rats. When male RC cells were treated
      with 17 beta, [3H]-thymidine incorporation was inhibited; however, when these
      cells were pretreated with 24,25 for 48 h, 17 beta stimulated [3H]-thymidine
      incorporation 24,25 had no effect on 17 beta-dependent [3H]-thymidine
      incorporation by female RC cells. 17 beta stimulated ALPase in female GC cells,
      but had no effect on male GC cells. 1,25 pretreatment of female GC cells
      inhibited the stimulatory effect of 17 beta on ALPase, but had no effect on
      ALPase in male GC cultures. 17 beta had no effect on male RC cell ALPase and
      stimulated ALPase in female RC cells. This was not affected by pretreatment with
      24,25. Pretreatment with 1,25 increased the basal level of sulfate incorporation
      only in female GC. No effect was found in RC cells. These results indicate that
      pretreatment of rat costochondral chondrocytes with vitamin D metabolites
      modulate the effect of 17 beta. Although the effect of vitamin D metabolites
      alone on these chondrocytes is maturation-dependent and not sex-specific, the
      influence of preincubation with vitamin D metabolites on the effect of 17 beta is
      hormone-specific, sex-specific, and maturation-dependent.

PMID- 9549048
TI  - Recruitment of individually (all-or-none) responding cells, rather than amplitude
      enhancement, is the single-cell mechanism subserving the dose-responsive
      activation of intracellular calcium second messenger signaling by the human
      luteinizing-hormone receptor.
AB  - We have investigated at the single-cell level how the human LH receptor mediates
      a dose-responsive increase in intracellular free calcium-ion concentrations
      ([Ca2+]i). In human embryonic kidney cells (293 cells) stably transfected with
      the full-length human LH receptor cDNA. Intact dimeric LH, but not LH beta- or
      alpha-subunits, evoked specific [Ca2+]i signals. High-resolution fluorescence
      (fura-2) video-microscopy demonstrated cell-to-cell variability in [Ca2+]i
      signaling responses in individual cells, viz., an all-or-none spike (9%), spike
      and-plateau (25%), or plateau (52%) types of temporal signal. Oscillatory [Ca2+]i
      responses were observed in 12-14% of LH-stimulated cells unrelated to LH
      concentration. The LH dose-response originated by higher concentrations of LH
      recruiting more individually responding cells (rather than altering [Ca2+]i
      signal amplitude), and eliciting a [Ca2+]i rise more rapidly, i.e., at reduced
      latency. Cobalt did not abolish the LH-stimulated [Ca2+]i spike-and-plateau
      response, but decreased the percentage of cells with a plateau pattern. Quench
      experiments demonstrated influx of Mn2+ following the [Ca2+]i spike, thus
      directly documenting divalent cation inflow during the plateau phase. Adenylyl
      cyclase activation with forskolin or treatment with a cAMP analog failed to
      elicit the biphasic [Ca2+]i response, and pertussis toxin (PTX) did not alter LH
      stimulated [Ca2+]i signaling. However, overnight preincubation with LH reduced
      the percentage of [Ca2+]i-responding cells following re-exposure to LH to 5.7%
      (vs 72% in control), suggesting LH-induced desensitization of the LH-receptor
      directed [Ca2+]i signal. In summary, the present studies of human LH receptor
      signal transduction at the single-cell level show that increasing concentrations
      of LH achieve a dose-dependent intracellular Ca2+ signaling response by
      recruiting an increasing number of [Ca2+]i-responding cells, while concomitantly
      decreasing the temporal latency of the biphasic [Ca2+]i signal without altering
      the amplitude of its spike phase. Prolonged exposure to LH appears to desensitize
      the LH receptor-driven [Ca2+]i signal.

PMID- 9549049
TI  - Differential effects of estrogen and medroxyprogesterone on basal and stress
      induced growth hormone release, IGF-1 levels, and cellular immunity in
      postmenopausal women.
AB  - We evaluated the influence of continual estrogen replacement therapy (ERT) as
      presently practiced by postmenopausal women with conjugated estrogens and
      medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth
      factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women
      were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and
      MPA). In the women receiving only conjugated estrogens, increased GH levels and
      decreased IGF-1 levels were found, which replicated previous research and
      probably reflected estrogen inhibition of hepatic IGF-1 production with a
      secondary increase in GH release because of reduced feedback inhibition. In women
      taking both MPA and estrogen, GH was increased and the previously observed
      estrogen induced decrease in IGF-1 levels was inhibited. In order to determine
      the influence of ERT on psycho-social stress-induced GH release, math (mental
      stress) and speech (social stress) challenges were utilized, and they produced
      significant increases in heart rate in all three groups. The heart rate following
      stress was significantly enhanced by estrogen replacement. These stressors also
      led to increased GH secretion in the women taking estrogen and MPA, but not in
      the other two groups. Gonadal steroids and GH can influence cellular immunity. We
      observed that ERT in both groups was associated with significantly enhanced
      lymphocyte responsiveness to the T-cell mitogens phytohemaglutinin (PHA) and
      Conconavalin A (Con A), and basal GH levels were correlated with the PHA response
      in the estrogen only group. ERT did not influence natural killer (NK) cell
      activity. We also found significant differences in the steady-state expression of
      latent Epstein-Barr virus (EBV) with increased antibody titers in the women in
      the estrogen only group and lower antibody titers in the MPA plus estrogen group.
      GH levels were correlated with EBV antibody titers in the estrogen plus MPA
      group. This study supports the hypothesis that GH and immune modulation can be
      influenced by ERT in postmenopausal woman. Given the extant literature on the
      immune-enhancing effects of GH, these data suggest that ERT may slow the decline
      of GH secretion with aging, an event that has been implicated in
      immunosenescence.

PMID- 9549050
TI  - Gonadotrophin and prolactin secretion in castrated male sheep following
      subcutaneous or intracranial treatment with testicular hormones.
AB  - Interactions between testosterone, estradiol, and inhibin in the control of
      gonadotrophin secretion in males are poorly understood. Castrated rams were
      treated with steroid-free bovine follicular fluid (bFF), testosterone, or
      estradiol and for 7 d (2 x 2 x 2 factorial design). Given independently, none of
      the exogenous hormones affected follicle-stimulating hormone (FSH)
      concentrations, but the combination of one or both steroids with bFF reduced FSH
      secretion. Testosterone and estradiol reduced luteinizing hormone (LH) pulse
      frequency (there was no synergism), and bFF had no effect. Plasma prolactin
      concentrations were not affected by any treatment. To locate the central sites of
      steroid action, castrated rams were bilaterally implanted in the preoptic area
      (POA), ventromedial nucleus (VMH), or arcuate nucleus (ARC). These implants did
      not affect FSH or prolactin concentrations, or LH pulse amplitude. The frequency
      of the LH pulses was not affected by testosterone in any site. Estradiol located
      in the ARC, but not the POA or VMH, decreased LH pulse frequency. In summary, FSH
      secretion is controlled by synergistic interactions between inhibin and estradiol
      or testosterone, whereas GnRH/LH pulse frequency is controlled by testicular
      steroids. Estradiol acts partly, at least, in the ARC, but the central site of
      action, testosterone remains unknown.

PMID- 9549052
TI  - Decreased insulin content and secretion in RIN 1046-38 cells overexpressing alpha
      2-adrenergic receptors.
AB  - Several Gi-protein-coupled receptors normally expressed in islet beta-cells
      inhibit insulin secretion on binding of their respective agonists. To study the
      effect of supraphysiologic expression of such a receptor in insulin-secreting
      beta-cells, we stably transfected cDNA encoding the mouse alpha 2a-adrenergic
      receptor into RIN 1046-38 cells. Four different cell lines were selected, each
      overexpressing the alpha 2a-adrenergic receptor to varying degrees. Cell lines
      showing the highest level of receptor expression showed significantly reduced
      insulin content, and reduced basal and stimulated insulin secretion. Pertussis
      toxin (PTX) treatment of cells was able to reverse partially the reduced insulin
      secretory response. Our results suggest that overexpression of a Gi-protein
      coupled receptor in beta-cells causes tonic inhibition of both insulin synthesis
      and secretion. Abnormalities in expression or function of such receptors could be
      a contributory factor in the impaired insulin secretion present in type II
      diabetes.

PMID- 9549051
TI  - Nicotinic activation of CRH neurons in extrahypothalamic regions of the rat
      brain.
AB  - Nicotine is known to have multiple effects on neuroendocrine, autonomic, and
      behavioral responses. Its neuroendocrine effect on the stress-responsive hormone,
      ACTH, depends on central pathways that act on corticotropin-releasing hormone
      (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN). Other CRH
      neurons throughout the brain also are involved in coordinating aspects of the
      stress response, but very little is known about the effect of nicotine on CRH
      neurons in extrahypothalamic regions that are involved in the autonomic and
      behavioral responses to stress. The current study sought to determine the extent
      of nicotinic activation of extrahypothalamic CRH neurons, since these neurons may
      be involved in mediating the central effects of nicotine. Freely moving rats were
      pretreated with a low dose of colchicine, infused with nicotine (0.045 mg/kg/30 s
      or 0.135 mg/kg/90 s, i.v.), and cardiac perfused 1 h later. Double-label
      immunocytochemistry identified the activated (positive for cFos protein) CRH
      neurons in limbic structures (bed nucleus of the stria terminalis [BNST] and
      central nucleus of the amygdala [CNA]), the dorsal raphe (DR), and Barrington's
      nucleus (BN); comparisons were made to the PVN. In all of these areas, nicotine
      activated CRH neurons in a dose-dependent manner, showing differential
      sensitivity and efficacy with respect to region. CNA CRH neurons were most
      responsive and were maximally stimulated by the low dose of nicotine (62% of CRH
      neurons were cFos+, compared to 10-27% of the CRH population in other regions,
      including the PVN). Although the BNST also was activated by the low dose, only
      the non-CRH+ neurons were involved; in contrast, 41% of the BNST CRH neurons
      responded to the higher dose. Nicotinic activation of DR neurons was dose
      dependent, with 22% of the CRH neurons activated by the high dose. Few BN neurons
      were activated by the low dose of nicotine, but 26% of the CRH population
      responded to the higher dose. These results indicate that the effect(s) of
      nicotine on the brain may be mediated, in part, by the selective activation of
      specific extrahypothalamic regions containing CRH neurons that also are involved
      in autonomic and behavioral responses to stress. The large fraction of CRH
      neurons responding to the low dose of nicotine in the CNA suggests that this
      limbic region may be particularly important in mediating these CNS effects of
      nicotine.

PMID- 9549054
TI  - Lethal P-lacZ insertion lines expressed during pattern respecification in the
      imaginal discs of Drosophila.
AB  - The imaginal discs of Drosophila are a useful experimental system in which we can
      study the origin and genetic determination of spatial patterns in development.
      This involves the separation of the disc-cell population into distinct lineage
      compartments, based on clonally transmitted expression states of a number of
      known selector genes. However, these commitments can be abrogated and the
      compartment boundaries redeployed, when repatterning occurs in cultured disc
      fragments. This has so far only been explained using the idea of positional
      information. The genetic basis of this property of the imaginal disc system and
      its relationship to compartments have not been identified. Here we have screened
      over 470 recessive lethal P-lacZ enhancer-trap insertions from the Berkeley
      Drosophila Genome Project for expression after cell death, which initiates
      pattern respecification in the imaginal discs. The positive lines obtained
      identify essential genes that may be important for pattern formation. Most show
      patterned imaginal disc expression, and many have maternal or zygotic effects on
      embryonic development. One is an allele of schnurri, a gene that encodes a
      component of the decapentaplegic (dpp) signal transduction pathway used for
      positional signalling in the embryo and in imaginal discs.

PMID- 9549053
TI  - Serotonin directly stimulates luteinizing hormone-releasing hormone release from
      GT1 cells via 5-HT7 receptors.
AB  - Luteinizing hormone-releasing hormone (LHRH release, which serves as the primary
      drive to the hypothalamic-pituitary gonadal axis, is controlled by many
      neuromediators. Serotonin has been implicated in this regulation. However, it is
      unclear whether the central effect of serotonin on LHRH secretion is exerted
      directly on LHRH neurosecretory neurons or indirectly via multisynaptic pathways.
      The present studies were undertaken in order to examine whether LHRH secretion
      from immortalized LHRH cell lines is directly regulated by serotonin and, if so,
      to identify the receptor subtype involved. 8-hydroxy-2-(di-n-propylamino)tetralin
      (8-OH-DPAT), a 5-HT1A/7 receptor agonist, stimulated LHRH release from GT1-1
      cells. This effect was blocked by ritanserin, a 5-HT2/7 receptor antagonist, but
      not by SDZ-216-525, a 5-HT1A antagonist. Basal LHRH release was not affected by
      the 5-HT2 agonist DOI. Reverse transcription and polymerase chain reaction
      technique (RT-PCR) was used in order to identify 5-HT1A and 5-HT7 receptor mRNA
      in immortalized LHRH cell lines. GT1-1 cells express mRNA for the 5-HT7, but not
      the 5-HT1A receptor subtypes. These results demonstrate a direct stimulatory
      effect of serotonin on LHRH release via 5-HT7 receptor.

PMID- 9549055
TI  - B-chromosome origin in the endemic New Zealand frog Leiopelma hochstetteri
      through sex chromosome devolution.
AB  - The endemic New Zealand frog Leiopelma hochstetteri has variable numbers of
      mitotically stable B chromosomes. To assess whether the B chromosomes were
      derived from the autosome complement, they were isolated by micromanipulation and
      their DNA amplified by degenerate oligonucleotide primed PCR. Southern
      hybridizations of B chromosome DNA probes to genomic DNA from males and females
      characterized by differing numbers of B chromosomes demonstrated that the B
      chromosomes were derived from the univalent W sex chromosome characteristic of
      North Island populations. The presence of homologous B chromosome specific
      sequences from geographically distinct populations indicates a single origin of
      the B chromosomes. Furthermore, a primitive homology shared by B chromosomes and
      the W sex chromosome from an ancestral WZ/ZZ karyotype, which is still present in
      frogs from Great Barrier Island, shows that the B chromosomes originated soon
      after the univalent W sex chromosome had originated. Sequence analysis revealed
      that B chromosome DNA is composed of repeat sequences and has the potential to
      form stable hairpin structures. The molecular dynamics of these structures may
      reflect an inherent propensity to undergo rapid change in nucleotide sequence and
      chromosome structure.

PMID- 9549056
TI  - An apparent case of nonsymmetrical and sustained strand-specific hemimethylation
      in the Dc8 gene of carrot.
AB  - The Dc8 gene of carrot (Daucus carota L.) shows differential expression during
      embryo development. Changes in methylation patterns of a segment of about 500 bp
      (from base +120 to base -446) of Dc8 allele 6 were investigated by treating
      genomic DNA, extracted from embryogenic callus at different stages of
      development, with sodium bisulfite to modify nonmethylated cytosines. Following
      asymmetric (strand-specific) amplification, base sequences for samples from each
      developmental stage were determined for each strand directly from the PCR
      products or from cloned PCR products. Different methylation patterns were
      detected in the two strands. The 5' to 3' sense (coding) strand was almost
      completely nonmethylated, whereas almost all the cytosines in the 3' to 5'
      (template) strand were methylated. By 71 days after transfer to embryo-inducing
      medium, few methylcytosines remained; those that were present were generally near
      the TATA box or in a region beyond -300. The cytosines that were methylated were
      not limited to CG or CNG sequences. The difference in the extent of methylation
      between the two complementary strands implies either that there is a mechanism
      for strand-specific methylation, or that complementary sequences can differ
      greatly in sensitivity to bisulfite treatment or PCR amplification.

PMID- 9549057
TI  - Characterization of MboI satellites in Cirrhina mrigala and Clarias batrachus
      (Pisces).
AB  - We have cloned and characterized two highly reiterated, tandemly repeated, and
      A+T rich MboI DNA fragments, one in Cirrhina mrigala (Cyprinidae), with a monomer
      size of 266 bp, and one in Clarias batrachus (Clariidae), with a monomer size of
      227 bp. The MboI fragment in C. mrigala is species-specific and absent in other
      carps, such as Catla catla and Labeo rohita. The MboI fragment in C. batrachus
      was also present in two other catfishes tested, namely Clarias gariepinus and
      Heteropneustes fossilis. In C, mrigala x C. catla and C. mrigala x L. rohita
      hybrids, the C. mrigala specific MboI fragment is inherited uniparentally. In the
      reciprocal hybrids of C. batrachus x H. fossilis, the satellite ladder contains
      the bands of both parental species. The MboI satellite of carp may be useful in
      genetic introgression analysis and that of catfish in distinguishing between
      gynogenetic progeny and true hybrids.

PMID- 9549059
TI  - Collinearity between a 30-centimorgan segment of Arabidopsis thaliana chromosome
      4 and duplicated regions within the Brassica napus genome.
AB  - Arabidopsis thaliana (the model dicotyledonous plant) is closely related to
      Brassica crop species. Genome collinearity, or conservation of marker order,
      between Brassica napus (oilseed rape) and A. thaliana was assessed over a 7.5-Mbp
      region of the long arm of A. thaliana chromosome 4, equivalent to 30 cM.
      Estimates of copy number indicated that sequences present in a single copy in the
      haploid genome of A. thaliana (n = 5) were present in 2-8 copies in the haploid
      genome of B. napus (n = 19), while sequences present in multiple copies in A.
      thaliana were present in over 10 copies in B. napus. Genetic mapping in B. napus
      of DNA markers derived from a segment of A. thaliana chromosome 4 revealed
      duplicated homologous segments in the B. napus genome. Physical mapping in A.
      thaliana of homologues of Brassica clones derived from these regions confirmed
      the identity of six duplicated segments with substantial homology to the 7.5-Mbp
      region of chromosome 4 in A. thaliana. These six duplicated Brassica regions (on
      average 22 cM in length) are collinear, except that two of the six copies contain
      the same large internal inversion. These results have encouraging implications
      for the feasibility of shuttling between the physical map of A. thaliana and
      genetic maps of Brassica species, for identifying candidate genes and for map
      based gene cloning in Brassica crops.

PMID- 9549060
TI  - Characterization of a microsatellite in the promoter region of the IGF1 gene in
      domestic horses and other equids.
AB  - Insulin-like growth factor 1 (IGF1) regulates growth and metabolic functions in
      vertebrates. A dinucleotide repeat sequence located at the promoter region of the
      IGF1 gene has been reported in several vertebrate species and may affect the
      control of the transcriptional activity of this gene. The genotypes of animals
      from seven horse breeds were determined in order to study the potential
      association of allelic forms of this microsatellite with adult body size
      differences found in domestic horses. Among these breeds, five alleles were
      found. Breed-specific differences in adult body size could not be attributed to
      the presence or absence of any of the alleles observed. In addition, animals
      representing five other equid species were typed. Examples of apparent species
      specific alleles were found. However, overlapping polymorphic size ranges
      preclude this microsatellite from being an absolute identifier for species or
      hybrid status in equids. The polymorphisms found at this IGF1 locus are useful
      for synteny and linkage mapping.

PMID- 9549061
TI  - Chromosome pairing in inter-racial hybrids of the house musk shrew (Suncus
      murinus, Insectivora, Soricidae).
AB  - Two chromosome races of the house shrew Suncus murinus that differ from each
      other for five Robertsonian translocations (8.17, 9.13, 10.12, 11.16, and 14.15),
      heterochromatic insertions in chromosomes 7 and X, and multiple rearrangements in
      the Y chromosome were crossed and then intercrossed in captivity to produce a
      hybrid stock. Electron-microscopic analysis of synaptonemal complexes in fertile
      and sterile hybrid males was carried out. Meiosis in sterile males did not
      progress beyond pachytene and was severely disrupted. Meiotic arrest was not
      determined by structural heterozygosity: heterozygotes for all variant
      chromosomes distinguishing two parental races were found in both sterile and
      fertile male hybrids. Fertile hybrids demonstrated an orderly pairing of all
      chromosomes. In heterozygotes for Robertsonian fusions, completely paired
      trivalents were formed between the Robertsonian metacentrics and homologous
      acrocentrics. In heterozygotes for chromosome 7, bivalents with a small buckle
      were observed in a small fraction of pachytene cells. No differences were found
      in the morphology and pairing pattern of sex bivalents, composed of the X and Y
      chromosomes derived from the same or different parental races. Univalents,
      multivalents, and associations between X and Y chromosomes and autosomal
      trivalents, as well as associations of autosomal trivalents with each other, were
      observed in a small fraction of the pachytene cells of fertile males. Our results
      indicate that the system controlling male sterility in interracial hybrids of S.
      murinus is of genic rather than of chromosomal type.

PMID- 9549062
TI  - Development of sequence characterized DNA markers linked to a dominant
      verticillium wilt resistance gene in tomato.
AB  - Sequences were determined for codominant RAPD markers closely linked to the Ve
      locus, a dominant verticillium wilt resistance gene in tomato. Analysis of the
      sequences linked to Ve and ve revealed a perfectly homologous sequence with a
      central polymorphic region comprising 79 nucleotide substitutions, insertions,
      and deletions. Codominant and allele-specific SCARs were developed using
      conserved and polymorphic sequences linked to the Ve locus. High resolution
      linkage analysis using F2 progeny segregating for resistance and marker-assisted
      selection indicated that linkage between the genetic markers and the Ve locus is
      less than 0.67 +/- 0.49 cM. Sequences were useful in determining the molecular
      structure of a polymorphic genomic region closely linked to the Ve locus and in
      developing genetic markers that facilitated marker-assisted selection of the
      resistant, susceptible, heterozygous, and homozygous genotypes.

PMID- 9549063
TI  - [Natural hybridization between two subspecies of the house mouse, Mus musculus
      domesticus and Mus musculus castaneus, near Lake Casitas, California].
AB  - The house mouse Mus musculus is a polytypic species, distributed worldwide, with
      three main subspecies: M. m. musculus in the North-East of Eurasia, M. m.
      castaneus in South-East Asia, and M. m. domesticus in Europe, the Near-East, and
      Africa. This last subspecies may also be found in Australia and the Americas,
      where it was brought by European colonization. Previous studies, however, have
      shown the presence of specific antiviral determinants of Asian origin in a mouse
      population at Lake Casitas, California. In this study, an analysis of the
      variability at 35 enzyme loci demonstrates the hybrid nature of this Californian
      population intermediate between M. m. castaneus and M. m. musculus. Restriction
      fragment length polymorphisms of two fragments of the mitochondrial DNA also
      confirm unambiguously the presence of two types of matrilines in comparable
      frequencies in our sample. Nevertheless, the study of a subspecies-specific Y
      chromosome microdeletion in the Zfy2 gene reveals only the M. m. domesticus
      haplotype at Lake Casitas, a phenomenon comparable with the one observed in other
      hybrid zones of the M. musculus complex. These findings testify once more that
      genetic exchanges between subspecies inside the broader M. musculus gene pool are
      still possible.

PMID- 9549064
TI  - Identification, characterization, and mapping of Ecm1, a locus affecting
      extracellular matrix production and lesion size in Cochliobolus heterostrophus.
AB  - A mutant of Cochliobolus heterostrophus lacking the outer layer of extracellular
      matrix around its germ tubes and hyphae was obtained by mutagenizing protoplasts.
      The mutant not only lacks the outer matrix, but also produces much smaller
      lesions on corn leaves than nonmutant strains; the area of mutant lesions
      averages 0.6 mm2 compared with 5.8 mm2 for nonmutant lesions. Genetic analysis
      demonstrated that the failure to produce the outer matrix cosegregates with the
      reduced lesion size, indicating that the two traits are controlled by the same
      locus, designated Ecm1 (Extracellular Matrix Deficient). The mutant retains
      normal growth on media and normal abilities to germinate, form appressoria, and
      penetrate corn leaves. This indicates that the outer matrix is not necessary for
      infection prior to entrance of the fungus into the leaf. It also indicates that
      the pathogenicity defect in this mutant is manifested after penetration. To
      facilitate future tests of whether the pathogenicity defect is caused by the lack
      of the outer matrix, Ecm1 was mapped. Seven markers linked to Ecm1 were found by
      analysis of amplified fragment length polymorphisms. Ecm1 maps to chromosome 4;
      the closest markers to Ecm1 are 5 cM distant, which is estimated to represent
      about 115 kb.

PMID- 9549065
TI  - Genome-specific repetitive DNA and RAPD markers for genome identification in
      Elymus and Hordelymus.
AB  - We have developed RFLP and RAPD markers specific for the genomes involved in the
      evolution of Elymus species, i.e., the St, Y, H, P, and W genomes. Two P genome
      specific repetitive DNA sequences, pAgc1 (350 bp) and pAgc30 (458 bp), and three
      W genome specific sequences, pAuv3 (221 bp), pAuv7 (200 bp), and pAuv13 (207 bp),
      were isolated from the genomes of Agropyron cristatum and Australopyrum
      velutinum, respectively. Attempts to find Y genome specific sequences were not
      successful. Primary-structure analysis demonstrated that pAgc1 (P genome) and
      pAgc30 (P genome) share 81% similarity over a 227-bp stretch. The three W genome
      specific sequences were also highly homologous. Sequence comparison analysis
      revealed no homology to sequences in the EMBL-GenBank databases. Three to four
      genome-specific RAPD markers were found for each of the five genomes. Genome
      specific bands were cloned and demonstrated to be mainly low-copy sequences
      present in various Triticeae species. The RFLP and RAPD markers obtained,
      together with the previously described H and St genome specific clones pHch2 and
      pP1Taq2.5 and the Ns genome specific RAPD markers were used to investigate the
      genomic composition of a few Elymus species and Hordelymus europaeus, whose
      genome formulas were unknown. Our results demonstrate that only three of eight
      Elymus species examined (the tetraploid species Elymus grandis and the hexaploid
      species Elymus caesifolius and Elymus borianus) really belong to Elymus.

PMID- 9549066
TI  - Nucleotide sequence and chromosomal mapping of the 5S rDNA repeat of the
      crustacean Proasellus coxalis.
AB  - In this investigation we analysed the 5S rRNA genes of the isopod crustacean
      Proasellus coxalis, 5S rDNA hybridization of digested genomic DNA and
      amplification by PCR demonstrate that these genes are organized in tandem repeats
      of 589 bp, 120 of which represent the coding sequence and 469 the spacer
      sequence. Proasellus coxalis is the first crustacean species in which 5S rRNA
      genes have been found tandemly arranged without being linked to other repeated
      genes. The PCR product has been used as a probe in FISH to locate the 5S rRNA
      genes on two chromosome pairs of the P. coxalis karyotype. Comparison of the 5S
      rRNA sequence of this species with previously published sequences of six other
      crustacean species shows the existence of a good correlation between phylogenetic
      relationships and sequence identity.

PMID- 9549067
TI  - H genome specific repetitive sequence, pEt2, of Elymus trachycaulus in part of
      Afa family of Triticeae.
AB  - The H genome specific repetitive sequence of Elymus trachycaulus, pEt2, consists
      of three units of a 337-339 bp repeat aligned in tandem. The sequence is
      homologous to Afa-family sequences that are widely distributed in the genomes of
      Triticeae (Gramineae) species.

PMID- 9549068
TI  - Reversed-phase ion-pair liquid chromatographic determination of chlorophacinone
      and diphacinone in steam-rolled oat baits and steam-rolled oat/wax baits.
AB  - A reversed-phase ion-pair liquid chromatographic (LC) method was developed for
      analysis of steam-rolled oat (SRO) baits fortified with either chlorophacinone or
      diphacinone. Baits were prepared with and without paraffin wax. Chlorophacinone
      or diphacinone was extracted from wax-free SRO baits with 5 mM tetrabutylammonium
      phosphate methanolic ion-pairing solution. Wax baits were initially extracted
      with petroleum ether and then cleaned up by liquid extraction into methanolic ion
      pairing solution containing 20% water. SRO extracts were analyzed with reversed
      phase ion-pair LC. Chlorophacinone and diphacinone were quantified by UV
      absorption at 325 nm. Recoveries from SRO fortified with chlorophacinone at 25
      and 150 micrograms/g were 90.7 and 90.8%, respectively, whereas for diphacinone
      at the same levels, recoveries were 93.5 and 92.3%, respectively. Recoveries from
      wax baits fortified at 25 and 75 micrograms/g chlorophacinone were 98.5 and 100%,
      respectively, whereas for diphacinone at the same levels, recoveries were 93.6
      and 98.0%, respectively. Method limits of detection for chlorophacinone and
      diphacinone in SRO baits were estimated to be 1.0 and 0.76 micrograms/g,
      respectively. Method limits of detection for chlorophacinone and diphacinone in
      wax baits were estimated to be 4.2 and 2.8 micrograms/g, respectively.

PMID- 9549069
TI  - Procedure for detecting and confirming pentobarbital residues in dog food by gas
      chromatography/mass spectrometry.
AB  - The method described detects and confirms presence of pentobarbital residues in
      dry, extruded feeds at concentrations of 5-20 ppb. Dried feed is ground to a
      uniform powder and shaken overnight in methanol. A portion of the methanolic
      extract is evaporated, and the residue is reconstituted in phosphate-buffered
      saline. The aqueous extract is cleaned with a solid-phase extraction cartridge
      designed to extract barbiturate residues from biological matrixes. Dimethyl
      sulfoxide, tetramethylammonium hydroxide, and iodomethane are added to derivatize
      pentobarbital, 1,3-Dimethyl-pentobarbital is then acidified with dilute
      hydrochloric acid and extracted with isooctane. The organic layer is transferred
      and evaporated under a stream of nitrogen. The residue is reconstituted in a
      small volume of ethyl acetate for analysis by gas chromatography/mass
      spectrometry. The limit of detection is approximately 0.7 ppb. The method was
      validated with pentobarbital-fortified feed samples containing high
      concentrations of meat and bone meal.

PMID- 9549070
TI  - A rapid and selective method for determining potential nitrosating agents in
      cosmetic products by chemiluminescence detection of nitric oxide.
AB  - A method was developed for rapid and selective determination of potential
      nitrosating agents at the part-per-billion level in cosmetic products. These
      compounds are chemically reduced to nitric oxide, which is determined by its
      chemiluminescent reaction with ozone. Suspended materials and colors in cosmetic
      products do not interfere. Hence their removal before analysis is not required. A
      detection limit of 33 ppb, calculated as nitrite, was obtained. No false-positive
      interferences were observed from antifoaming agents, several N-nitroso compounds,
      and nitrate up to 20 ppm. Among cosmetic products surveyed, potential nitrosating
      agents were found at levels ranging from 113 to 5021 ppb. No consistent
      relationship was found between levels of potential nitrosating agents and N
      nitrosamines in the same products. However, the highest levels of nitrosating
      agents were most often associated with the highest levels of N-nitrosamines known
      to be present in the products.

PMID- 9549071
TI  - Determination of reserpine and rescinnamine in Rauwolfia serpentina powders and
      tablets: collaborative study.
AB  - A liquid chromatographic (LC) method for determining reserpine and rescinnamine
      in Rauwolfia serpentine powders and tablets, which uses fluorescence detection,
      was subjected to a collaborative study. The procedure for extraction and
      purification is a simplified version of that used in the current official method
      for analysis of these products. LC separations are performed on a normal-phase
      column. The mobile phase is methanol to which a small volume of an aqueous
      solution of 1-pentanesulfonic acid sodium salt can be added to achieve desired
      elution characteristics. Reserpine and rescinnamine elute at approximately the
      same time but can be individually quantitated by appropriate settings of the
      fluorescence detector. Reserpine is determined at an excitation wavelength of 280
      nm and an emission wavelength of 360 nm, because rescinnamine is completely non
      fluorescent at these wavelengths. Rescinnamine is determined at an excitation
      wavelength of 330 nm and an emission wavelength of 435 nm, because reserpine is
      completely nonfluorescent at these wavelengths. The following materials were used
      for the study: one sample of United States Pharmacopeia (USP) standard R.
      serpentine powder, one tablet type labeled as containing 100 mg R. serpentine and
      2 tablet types labeled as containing 50 mg R. serpentine. For each of the 4
      materials, 2 pairs of blind duplicates were prepared. Three materials were
      analyzed in duplicate by 8 laboratories. One of the 2 tablets labeled to contain
      50 mg R. serpentine was analyzed only by 7 of 8 participating laboratories.
      Average combined content of reserpine and rescinnamine was 0.144% for the USP raw
      material and 0.132, 0.135, and 0.137% for the 3 commercial tablets.
      Reproducibility relative standard deviation values were 5.72, 5.93, 8.61, and
      3.48% and repeatability relative standard deviation values were 2.57, 4.87, 3.19,
      and 1.99% for the 4 samples. The Associate Referee conducted a study to determine
      recoveries of reserpine plus rescinnamine by this method from mixtures simulating
      sample extracts. Average recovery of 15 determinations was 100.1%, with a
      relative standard deviation of 1.3%. The LC method for determination of reserpine
      and rescinnamine in R. serpentine powders and tablets has been adopted first
      action by AOAC INTERNATIONAL.

PMID- 9549072
TI  - Simultaneous liquid chromatographic analysis of the beta-lactam antibiotics
      cefazolin, cefadroxil, cephalexin, ampicillin, and cephradine in solution.
AB  - A liquid chromatographic method was developed for the determination of nanogram
      quantities of 5 broad-spectrum structurally related beta-lactam antibiotics
      (cefazolin, cefadroxil, cephalexin, cephradine, and ampicillin) in solution. The
      method uses a C18 reversed-phase column, UV absorption (240 nm) detection, and an
      aqueous mobile phase containing isopropyl alcohol and acetic acid. Relative
      resolution between the antibiotic peaks ranged from 1.7 to 5.9 for all peaks.
      Chromatographic retention times were 2.97, 3.92, 4.57, 5.37, and 6.56 min for
      cefazolin, cefadroxil, cephalexin, ampicillin, and cephradine, respectively.
      Accuracy, precision, linearity, and long term analytical reproducibility were
      determined by statistical analysis. Use of the proposed method to evaluate the
      degradation of cephradine solutions stored at room temperature illustrated its
      potential as a stability-indicating assay.

PMID- 9549073
TI  - Optical immunobiosensor assay for determining enrofloxacin and ciprofloxacin in
      bovine milk.
AB  - A rapid, sensitive optical immunobiosensor assay was developed and used to
      determine enrofloxacin and its main metabolite, ciprofloxacin, in milk from
      healthy cows and cows with clinical signs of mastitis after intramuscular
      administration of enrofloxacin. Liquid chromatography (LC) was used to confirm
      results of the biosensor assay. Despite incomplete cross-reactivity between
      polyclonal enrofloxacin antibodies and ciprofloxacin, the biosensor assay could
      be used for semiquantitative analysis of the sum of the 2 substances. LC analysis
      showed that ciprofloxacin persisted at levels exceeding the expected future
      maximum residue limit in milk for several days after the end of the withdrawal
      period.

PMID- 9549074
TI  - Comparison of monolayer and bilayer plates used in antibiotic assay.
AB  - Standard curves of 5 antibiotics were determined in an antibiotic assay using
      bilayer and monolayer agar plates and AOAC-specified test organisms and agar
      media. Micrococcus luteus ATCC 9341a and antibiotic medium No. 2 were used to
      prepare the penicillin G standard curve. The same organism and antibiotic medium
      No. 11 were used to prepare the erythromycin standard curve. Standard curves for
      streptomycin, tetracycline, and gentamicin were prepared, respectively, with
      antibiotic medium No. 5 and Bacillus subtilis ATCC 6633, antibiotic medium No. 8
      and B. cereus ATCC 11778, and antibiotic medium No. 11 and Staphylococcus
      epidermidis ATCC 12228. Assays of inhibition by meat fortified with penicillin,
      streptomycin, gentamicin, tetracycline, erythromycin also were performed on
      monolayer and bilayer plates. Differences in standard curves and inhibitory
      responses obtained with monolayer and bilayer plates were < 10%. Thus, monolayer
      plates are acceptable for use in analyses of meat and poultry for antibiotics
      residues, with savings in laboratory resources and time.

PMID- 9549075
TI  - Direct 24-hour presumptive enumeration of Escherichia coli O157:H7 in foods using
      hydrophobic grid membrane filter followed by serological confirmation:
      collaborative study.
AB  - Fifteen laboratories took part in a collaborative study to validate a method for
      enumerating Escherichia coli O157:H7. The method is based on use of a hydrophobic
      grid membrane filter and consists of 24 h presumptive enumeration on SD-39 Agar
      and serological confirmation to yield a confirmed E. coli O157:H7 count. Six food
      products were analyzed: pasteurized apple cider, pasteurized 2% milk, cottage
      cheese, cooked ground pork, raw ground beef, and frozen whole egg. The test
      method produced significantly higher confirmed count results than did the
      reference method for milk, pork, and beef. Test method results were numerically
      higher than but statistically equivalent to reference method results for cheese,
      cider, and egg. The test method produced lower repeatability and reproducibility
      values than did the reference method for most food/inoculation level combinations
      and values very similar to those of the reference method for the remaining
      combinations. Overall, 94% of presumptive positive isolates from the test method
      were confirmed serologically as E coli O157:H7, and 98% of these were also
      biochemically typical of E. coli O157:H7 (completed test). Corresponding rates
      for the reference method were 69 and 98%, respectively. On the basis of the
      results of this collaborative study and the precollaborative study that preceded
      it, it is recommended that this method be adopted official first action for
      enumeration of E. coli O157:H7 in meats, poultry, dairy foods, infant formula,
      liquid eggs, mayonnaise, and apple cider.

PMID- 9549076
TI  - LOCATE enzyme-linked immunosorbent assay for detection of Salmonella in food:
      collaborative study.
AB  - A collaborative study was performed in 27 laboratories to validate the enzyme
      linked immunosorbent procedure LOCATE for rapid detection of Salmonella in foods.
      Results were read visually and with a microtiter plate reader. The LOCATE method
      was compared with the Bacteriological Analytical Manual (BAM)/AOAC INTERNATIONAL
      culture method for detecting Salmonella in 6 foods: milk chocolate, nonfat dry
      milk, dried whole egg, soy flour, ground black pepper, and ground raw turkey. Two
      foods--dried whole egg and black pepper--required repeat rounds because
      insufficient data sets were produced initially (AOAC INTERNATIONAL stipulates a
      minimum of 15 sets per food type). Each laboratory tested one or more of the 6
      foods. A total of 1 439 samples were analyzed, and no significant differences (P
      < 0.05) were observed between LOCATE with either visual or reader detection and
      BAM/AOAC INTERNATIONAL results. The LOCATE screening method with visual or reader
      detection is recommended for Official First Action Approval.

PMID- 9549077
TI  - Comparison of the VITEK Gram-Negative Identification Card and an enhanced version
      for identification of Salmonella, Escherichia coli, and other Enterobacteriaceae:
      method modification.
AB  - The VITEK Gram-Negative Identification Card (GNI) was compared to an enhanced
      version of the test kit, the GNI + Card. The GNI Card is an official AOAC method
      (991.13) for identification of Salmonella, Escherichia coli, and other
      Enterobacteriaceae in foods. In this comparison 5 replicates of 124 gram-negative
      stock culture strains were evaluated to determine equivalency. Isolates were
      obtained primarily from food sources, with 108 of the isolates representing 15
      genera within the family Enterobacteriaceae. Overall agreement between the GNI
      Card and the GNI + Card was 98.2%. Of the 23 strains of Salmonella tested, the
      longest identification time for the GNI Card was 10 h, with 43.5% of the strains
      identifying in 4 h or less. The longest identification time of the same
      Salmonella strains tested with the GNI + Card was 8 h, with 95.7% of the strains
      identifying within 4 h. The GNI + Card provided increased speed of identification
      while retaining the accuracy of the GNI Card. The GNI method for identifying
      Salmonella, Escherichia coli, and other Enterobacteriaceae was approved as a
      method modification by AOAC INTERNATIONAL.

PMID- 9549078
TI  - Determination of diarrheic shellfish toxins in mussels by microliquid
      chromatography-tandem mass spectrometry.
AB  - A fast, sensitive, and specific procedure for determining toxins that cause
      diarrheic shellfish poisoning (DSP) using microliquid chromatography coupled with
      tandem mass spectrometry (micro-LC-MS-MS) is reported. The lipophylic polyether
      acidic toxins okadaic acid (OA), its isomer dinophysistoxin-2 (DTX-2), the 35
      methylokadaic acid dinophysistoxin-1 (DTX-1), and the novel toxin dinophysistoxin
      1B (DTX-2B; recently isolated from Irish mussels) were extracted from shellfish
      tissues with acetone and chromatographed by isocratic elution at 10 microL/min
      with CH3 CN-H2O, 80 + 20 (v/v), containing 0.1% trifluoroacetic acid, through a
      C18 reversed-phase column (1.0 mm id). The chromatograph is coupled via an ion
      spray interface to an atmospheric pressure ionization source. Collision-induced
      dissociation (CID) ion mass spectra of the protonated molecule, [M + H]+, at m/z
      805 for OA, DTX-2, and DTX-2B and at m/z 819 for DTX-1, were obtained in MS-MS
      experiments to identify 2 diagnostic fragment ions for each analyte that could be
      used for selected-reaction-monitoring (SRM) micro-LC-MS-MS analysis. The CID
      spectrum of DTX-2B confirmed it to be a new OA isomer, like DTX-2. Standard
      curves obtained by SRM micro-LC-MS-MS were linear (r2 > or = 0.9992) over the
      range 0.05-1.00 micrograms/mL (i.e., 0.10-2.00 micrograms toxin/g
      hepatopancreas), and a detection limit of 15 pg/injection was obtained for each
      DSP toxin. Average recoveries ranged from 95 to 101%, and coefficients of
      variation ranged from 1.8 to 3.4%. This novel SRM micro-LC-MS-MS method was used
      to confirm acidic DSP toxins in Irish and Italian toxic mussels. It offers a high
      degree of specificity because analyte confirmation is based on retention time,
      molecular weight, structural information obtained from the presence of 2
      diagnostic fragments for each analyte, and ion ratios. OA was found in both Irish
      (< or = 0.7 micrograms/g hepatopancreas) and Italian (< or = 1.5 micrograms/g
      hepatopancreas) mussels. DTX-1 was found only in Italian mussels (< or = 0.3
      micrograms/g hepatopancreas). DTX-2 (< or = 6.1 micrograms/g hepatopancreas) and
      DTX-2B (< or = 0.08 micrograms/hepatopancreas) were unique to Irish shellfish.

PMID- 9549079
TI  - One-step solid-phase extraction cleanup and fluorometric analysis of
      deoxynivalenol in grains.
AB  - A rapid, quantitative, inexpensive, efficient method was developed to determine
      deoxynivalenol (DON) in wheat, barley, corn, wheat middlings, wheat flour, bran,
      malted barley, and oats. Samples are ground and extracted with acetonitrile-water
      (86 + 14). A portion of the extract is cleaned up by passage through a MycoSep
      No. 225 column, evaporated to dryness, and derivatized with zirconyl nitrate and
      ethylenediamine in methanol. The resulting fluorescent derivative of DON is
      identified and quantitated with a calibrated fluorometer containing a broad
      wavelength pulsed xenon light source. This method quantitated DON concentrations
      from 0.5 to 50 ppm without dilution and was linear when applied to samples of
      noncontaminated wheat spiked at 0.5, 5, 10, 25, and 50 micrograms DON/g.
      Correlation coefficients of the method with LC for multiple analyses (n > or = 14
      for each commodity) applied to wheat, corn, barley, wheat flour, and wheat
      middlings were 0.99, 0.99, 0.99, 0.93, and 0.98, respectively. Individual
      analyses were conducted in < 30 min, and 24 samples were analyzed in 2 h.

PMID- 9549080
TI  - Zero control reference materials for infant formula methods development.
AB  - A zero control reference material (ZRM) for milk and soy-based infant formula was
      manufactured and characterized. The ZRM was free of retinyl palmitate and all-rac
      alpha-tocopheryl acetate. The composition was similar to commercially available
      infant formula. The ZRM provides a valuable tool to ascertain method performance.

PMID- 9549081
TI  - Optimization of selenium determination in human milk and whole blood by flow
      injection hydride atomic absorption spectrometry.
AB  - A flow injection hydride atomic absorption spectrometric (FI-HAAS) method was
      developed for determining selenium in human milk and whole blood after microwave
      digestion of the sample. The sample (2 mL human milk or 0.25 mL blood) was
      introduced into the microwave vessel with 1.5 mL HNO3 and 0.25 mL H2O2 and 300 W
      (4 min) and 600 W (4 min) were applied. The digestion was completed by heating to
      140 degrees C (2-3 h). Se (VI) was reduced to Se (IV) with hydrochloric acid. The
      instrumental conditions for FI-HAAS (concentrations of reducing agent and carrier
      acid, flow rate of argon carrier gas, and sample volume injected) were optimized.
      The detection limit of the proposed method was 0.23 ng/mL (assay) or 115 pg Se
      (absolute) in biological samples (1.15 ng/mL milk, 10.4 ng/mL blood). The
      precision values were 5.0% for milk and 4.0% for blood. The accuracy was
      evaluated with 2 reference materials, National Institute of Standards and
      Technology Non-Fat Milk Powder (found: 104.3 +/- 7.2 ng/g, certified: 110 +/- 10
      ng/g) and Whole Blood Seronorm (found: 81 +/- 7.3 ng/mL, reference: 83 +/- 4
      ng/mL). The results show the suitability of the method for selenium determination
      in human milk and whole blood. The method was applied to whole blood samples
      obtained from pregnant women and to human milk.

PMID- 9549082
TI  - Ivermectin quantitation with an abamectin internal standard.
AB  - The potent antiparasitic ivermectin is detected at low concentrations (ng/g) in
      liver and muscle tissue by liquid chromatography after conversion to a
      fluorescent derivative with 1-methylimidazole and trifluoroacetic anhydride. This
      acetylation reaction can be compromised by residual water that leads to decreased
      yields. Yields of derivatives of ivermectin and abamectin, a related avermectin,
      are identical under all circumstances tested. Use of abamectin as an internal
      standard eliminates derivative yield as a source of analytical variation.

PMID- 9549083
TI  - Solid-phase extraction cleanup for ivermectin in liver tissue.
AB  - Extraction of liver tissue with organic solvent produces coextractants with
      compounds of interest. The solid-phase extraction (SPE) cleanup of liver tissue
      developed for ivermectin removes nonpolar coextractants. Liver extract that has
      been reduced to dryness is reconstituted in 0.5 mL acetonitrile. The mixture is
      passed through 0.1 g C18 SPE column, and the eluate is collected. The column is
      eluted further with 2 mL acetonitrile. Combined eluates are derivatized with 1
      methylimidazole and trifluoroacetic anhydride, and the ivermectin derivative is
      determined by liquid chromatography with fluorescence detection.

PMID- 9549084
TI  - Determination of 4-hexylresorcinol in crab meat.
AB  - A method is described for determining 4-hexylresorcinol in crab meat. 4
      Hexylresorcinol is used to prevent melanosis in shrimp, and the same use has been
      proposed for crab meat. Because 4-hexylresorcinol may be added illegally to crab
      meat as a preservative, consumer protection requires that residues of the
      compound be monitored in crab meat. 4-Hexylresorcinol is extracted from crab meat
      with acetonitrile. After dilution with water, the extract is passed through a C18
      solid-phase extraction column and 4-hexylresorcinol is eluted from the column
      with ethanol. The compound is determined by reversed-phase liquid chromatography
      with diode array detection at 206 nm. Limit of quantitation is 1.0 microgram/g.
      Mean recovery in the range 1-20 micrograms/g is 89%, with a relative standard
      deviation of 6.3.

PMID- 9549085
TI  - Microwave power absorption in a multilayered cylindrical model of man near a flat
      reflector.
AB  - There are usually objects in the vicinity when a person is exposed to
      electromagnetic waves. It is exceedingly difficult to calculate the whole-body
      average specific absorption rate (SAR) in the microwave frequency region using a
      realistic heterogeneous model of man. In this paper, we use a multilayered
      cylinder model to numerically examine the average SAR of an adult standing near a
      flat reflector exposed to microwave energy. We also offer a comparison with
      existing data from a realistic model for an E-polarized wave below 600MHz.

PMID- 9549086
TI  - Immunohistochemical identification of the cytoskeletal elements in the notochord
      cells of bony fishes.
AB  - The medulla of the unconstricted notochords of the shortnose sturgeon, Acipenser
      brevirostratus, and African lungfish, Protopterus annectens, and the cellular
      component of the intervertebral joint tissue of the teleost fish, Perca
      flavescens, are comprised of cells with a large central vacuole. Previous studies
      on the fine structure of this tissue revealed that the cytoplasm surrounding
      these vacuoles consists of 10-nm-diameter intermediate filaments. Since in
      mammals there are a large number of tissue-specific types of intermediate
      filaments, this study uses antibodies to mammalian intermediate filaments to
      determine the type of filaments present in the notochord cells of bony fishes.
      Positive labeling using a polyclonal antibody to human skin keratins is observed
      in the cytoplasm of the notochord cells in the intervertebral tissues of Perca.
      These tissues are also probed with the AE series antibodies that label keratins
      found in mammalian epithelial cells. In both Protopterus and Acipenser the
      peripheral cytoplasm of the notochord cells is labeled with all three AE
      antibodies. In Perca only the AE3 antibody probe produces positive staining.
      These staining patterns are consistent with previous studies on the localization
      of cytokeratins in fish tissues and indicate that the intermediate filaments in
      the notochord cells of bony fishes are immunologically similar to the mammalian
      keratins.

PMID- 9549087
TI  - The structural basis of molecular adaptation.
AB  - The study of molecular adaptation has long been fraught with difficulties, not
      the least of which is identifying out of hundreds of amino acid replacements
      those few directly responsible for major adaptations. Six studies are used to
      illustrate how phylogenies, site-directed mutagenesis, and a knowledge of protein
      structure combine to provide much deeper insights into the adaptive process than
      has hitherto been possible. Ancient genes can be reconstructed, and the
      phenotypes can be compared to modern proteins. Out of hundreds of amino acid
      replacements accumulated over billions of years those few responsible for
      discriminating between alternative substrates are identified. An amino acid
      replacement of modest effect at the molecular level causes a dramatic expansion
      in an ecological niche. These and other topics are creating the emerging field of
      "paleomolecular biochemistry."

PMID- 9549088
TI  - Phylogeny and biogeography of ratite birds inferred from DNA sequences of the
      mitochondrial ribosomal genes.
AB  - The origin of the flightless ratite birds of the southern continents has been
      debated for over a century. Whether dispersal or vicariance (continental breakup)
      best explains their origin depends largely on their phylogenetic relationships.
      No consensus has been reached on this issue despite many morphological and
      molecular studies. To address this question further we sequenced a 2.8-kb region
      of mitochondrial DNA containing the ribosomal genes in representative ratites and
      a tinamou. Phylogenetic analyses indicate that Struthio (Africa) is basal and
      Rhea (South America) clusters with living Australasian ratites. This phylogeny
      agrees with transferrin and DNA hybridization studies but not with sequence
      analyses of some protein-coding genes. These results also require reevaluation of
      the phylogenetic position of the extinct moas of New Zealand. We propose a new
      hypothesis for the origin of ratites that combines elements of dispersal and
      vicariance.

PMID- 9549089
TI  - Improved tests for heterogeneity across a region of DNA sequence in the ratio of
      polymorphism to divergence.
AB  - The neutral theory of molecular evolution predicts that the ratio of
      polymorphisms to fixed differences should be fairly uniform across a region of
      DNA sequence. Significant heterogeneity in this ratio can indicate the effects of
      balancing selection, selective sweeps, mildly deleterious mutations, or
      background selection. Comparing an observed heterogeneity statistic with
      simulations of the heterogeneity resulting from random phylogenetic and sampling
      variation provides a test of the statistical significance of the observed
      pattern. When simulated data sets containing heterogeneity in the polymorphism-to
      divergence ratio are examined, different statistics are most powerful for
      detecting different patterns of heterogeneity. The number of runs is most
      powerful for detecting patterns containing several peaks of polymorphism; the
      Kolmogorov-Smirnov statistic is most powerful for detecting patterns in which one
      end of the gene has high polymorphism and the other end has low polymorphism; and
      a newly developed statistic, the mean sliding G statistic, is most powerful for
      detecting patterns containing one or two peaks of polymorphism with reduced
      polymorphism on either side. Nine out of 27 genes from the Drosophila
      melanogaster subgroup exhibit heterogeneity that is significant under at least
      one of these three tests, with five of the nine remaining significant after a
      correction for multiple comparisons, suggesting that detectable evidence for the
      effects of some kind of selection is fairly common.

PMID- 9549090
TI  - A novel family of short interspersed repetitive elements (SINEs) from cichlids:
      the patterns of insertion of SINEs at orthologous loci support the proposed
      monophyly of four major groups of cichlid fishes in Lake Tanganyika.
AB  - Short interspersed repetitive elements (SINEs) have been shown to be excellent
      markers of molecular phylogeny, since the integration of a SINE at a particular
      position in a genome can be considered an unambiguous derived homologous
      character. In the present study, we isolated a new family of SINEs from cichlids
      in Lake Tanganyika, whose speciation and diversification have been regarded as
      prime examples of explosive adaptive radiation. Members of this new SINE family,
      which we named the AFC family, are about 320 bp in length, and each has a tRNA
      related region in its 5' region, as do most of the members of SINE families
      reported to date. A dot blot hybridization experiment showed that this family is
      distributed extensively in the genomes of cichlids in Africa, with estimated copy
      numbers of 2 x 10(3)-2 x 10(4) per haploid genome. Our investigations of the
      patterns of insertion of members of this family at six orthologous loci
      demonstrated clearly that four previously identified tribes, namely, the
      Lamprologini, Ectodini, Tropheini, and Perissodini, each form a monophyletic
      group. These results provide a basis for the elucidation of the phylogenetic
      framework of the cichlid fishes in Lake Tanganyika.

PMID- 9549091
TI  - Evolutionary divergence of AP-PCR (RAPD) patterns.
AB  - Rates at which AP-PCR patterns diverge among isolated taxa were examined to test
      whether they exhibit clocklike regularity. The results showed that rates of
      divergence differed significantly among the groups examined (primates, antelopes,
      and Hawaiian Drosophila grimshawi). Therefore, AP-PCR divergence rates cannot be
      used as a "universal clock" with an invariant rate in all animals. Nevertheless,
      within each group, a strong relationship existed between degree of AP-PCR pattern
      divergence and time since separation of isolated taxa. Thus, AP-PCR divergence
      may prove useful for dating evolutionary events if calibrated within a more
      limited taxon.

PMID- 9549092
TI  - Molecular characterization and phylogenetic relationships of a protein with
      potential oxygen-binding capabilities in the grasshopper embryo. A hemocyanin in
      insects?
AB  - Arthropodan hemocyanins, prophenoloxidases (PPOs), and insect hexamerins form a
      superfamily of hemolymph proteins that we propose to call the AHPH superfamily.
      The evolutionary and functional relationships of these proteins are illuminated
      by a new embryonic hemolymph protein (EHP) that is expressed during early stages
      of development in the grasshopper embryo. EHP is a 78-kDa soluble protein present
      initially in the yolk sac content, and later in the embryonic hemolymph. Protein
      purification and peptide sequencing were used to identify an embryonic cDNA clone
      coding for EHP. In situ hybridization identifies hemocytes as EHP-expressing
      cells. As deduced from the cDNA clone, EHP is a secreted protein with two
      potential glycosylation sites. Sequence analysis defines EHP as a member of the
      AHPH superfamily. Phylogenetic analyses with all the currently available AHPH
      proteins, including EHP, were performed to ascertain the evolutionary history of
      this protein superfamily. We used both the entire protein sequence and each of
      the three domains present in the AHPH proteins. The phylogenies inferred for each
      of the domains suggest a mosaic evolution of these protein modules. Phylogenetic
      and multivariate analyses consistently group EHP with crustacean hemocyanins and,
      less closely, with insect hexamerins, relative to cheliceratan hemocyanins and
      PPOs. The grasshopper protein rigorously preserves the residues involved in
      oxygen binding, oligomerization, and allosteric regulation of the oxygen
      transport proteins. Although insects were thought not to have hemocyanins, we
      propose that EHP functions as an oxygen transport or storage protein during
      embryonic development.

PMID- 9549094
TI  - Estimating divergence dates from molecular sequences.
AB  - The ability to date the time of divergence between lineages using molecular data
      provides the opportunity to answer many important questions in evolutionary
      biology. However, molecular dating techniques have previously been criticized for
      failing to adequately account for variation in the rate of molecular evolution.
      We present a maximum-likelihood approach to estimating divergence times that
      deals explicitly with the problem of rate variation. This method has many
      advantages over previous approaches including the following: (1) a rate constancy
      test excludes data for which rate heterogeneity is detected; (2) date estimates
      are generated with confidence intervals that allow the explicit testing of
      hypotheses regarding divergence times; and (3) a range of sequences and fossil
      dates are used, removing the reliance on a single calculated calibration rate. We
      present tests of the accuracy of our method, which show it to be robust to the
      effects of some modes of rate variation. In addition, we test the effect of
      substitution model and length of sequence on the accuracy of the dating
      technique. We believe that the method presented here offers solutions to many of
      the problems facing molecular dating and provides a platform for future
      improvements to such analyses.

PMID- 9549093
TI  - Out of Africa and back again: nested cladistic analysis of human Y chromosome
      variation.
AB  - We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
      individuals from Africa, Asia, Europe, Oceania, and the New World. Phylogenetic
      analyses of these nine sites resulted in a tree for 10 distinct Y haplotypes with
      a coalescence time of approximately 150,000 years. The 10 haplotypes were
      unevenly distributed among human populations: 5 were restricted to a particular
      continent, 2 were shared between Africa and Europe, 1 was present only in the Old
      World, and 2 were found in all geographic regions surveyed. The ancestral
      haplotype was limited to African populations. Random permutation procedures
      revealed statistically significant patterns of geographical structuring of this
      paternal genetic variation. The results of a nested cladistic analysis indicated
      that these geographical associations arose through a combination of processes,
      including restricted, recurrent gene flow (isolation by distance) and range
      expansions. We inferred that one of the oldest events in the nested cladistic
      analysis was a range expansion out of Africa which resulted in the complete
      replacement of Y chromosomes throughout the Old World, a finding consistent with
      many versions of the Out of Africa Replacement Model. A second and more recent
      range expansion brought Asian Y chromosomes back to Africa without replacing the
      indigenous African male gene pool. Thus, the previously observed high levels of Y
      chromosomal genetic diversity in Africa may be due in part to bidirectional
      population movements. Finally, a comparison of our results with those from nested
      cladistic analyses of human mtDNA and beta-globin data revealed different
      patterns of inferences for males and females concerning the relative roles of
      population history (range expansions) and population structure (recurrent gene
      flow), thereby adding a new sex-specific component to models of human evolution.

PMID- 9549095
TI  - Contrasting levels of DNA polymorphism at the autosomal and X-linked visual color
      pigment loci in humans and squirrel monkeys.
AB  - The X-linked color pigment (opsin) locus is known to be highly polymorphic in the
      squirrel monkey and other New World monkeys. To see whether this is also the case
      for the autosomal (blue) opsin locus, we obtained 32 squirrel monkey and 30 human
      blue opsin gene sequences. No amino acid polymorphism was found in either the
      squirrel monkey sample or the human sample, contrary to the situation at the X
      linked opsin locus. This sharp contrast in the level of polymorphism might be due
      to differences in gene expression between the autosomal and the X-linked loci. At
      the X-linked locus, heterozygote advantage can occur because, owing to X
      inactivation, the two alleles in a heterozygote are expressed in different cone
      cells, producing two types of cone cell, whereas at the autosomal locus,
      heterozygote advantage cannot occur because the two alleles in a heterozygote are
      expressed in the same cone cells, producing only one type of cone cell (i.e.,
      phenotypically a homozygote). From the sequence data, the levels of nucleotide
      diversity (pi, i.e., the number of nucleotide differences per site) are
      estimated: for the human sample, pi = 0.00% per nondegenerate site, 0.00% per
      twofold degenerate site, and 0.04% per fourfold degenerate site in the coding
      regions and 0.01% per site in intron 4; for the squirrel monkey sample, pi =
      0.00% per nondegenerate site, 0.00% per twofold degenerate site, and 0.15% per
      fourfold degenerate site in the coding regions and 0.17% per site in intron 4.
      The blue opsin genes from the common and pygmy chimpanzees, the gorilla, the
      capuchin, and the howler monkey were also sequenced. Features critical to the
      function of the opsin are well conserved in all known mammalian sequences.
      However, the interhelical loops are, on average, actually more conservative than
      the transmembrane helical regions. In addition, these sequence data and those
      from some other genes indicate that the common and pygmy chimpanzees are not
      closely related, their divergence data being from one third to one half the date
      of the human-chimpanzee divergence.

PMID- 9549096
TI  - A phylogenetic approach to the identification of phosphoglucomutase genes.
AB  - The expanding molecular database provides unparalleled opportunities for
      characterizing genes and for studying groups of related genes. We use sequences
      drawn from the database to construct an evolutionary framework for examining the
      important glycolytic enzyme phosphoglucomutase (PGM). Phosphoglucomutase plays a
      pivotal role in the synthesis and utilization of glycogen and is present in all
      organisms. In humans, there are three well-described isozymes, PGMI, PGM2, and
      PGM3. PGM1 was cloned 5 years ago; however, repeated attempts using both
      immunological approaches and molecular probes designed from PGM1 have failed to
      isolate either PGM2 or PGM3. Using a phylogenetic strategy, we first identified
      47 highly divergent prokaryotic and eukaryotic PGM-like sequences from the
      database. Although overall amino acid identity often fell below 20%, the relative
      order, position, and sequence of three structural motifs, the active site and the
      magnesium--and sugar-binding sites, were conserved in all 47 sequences. The
      phylogenetic history of these sequences was complex and marked by duplications
      and translocations; two instances of transkingdom horizontal gene transfer were
      identified. Nonetheless, the sequences fell within six well-defined evolutionary
      lineages, three of which contained only prokaryotes. Of the two
      prokaryotic/eukaryotic lineages, one contained bacterial, yeast, slimemold,
      invertebrate, and vertebrate homologs to human PGM1 and the second contained
      likely homologs to human PGM2. Indeed, an amino acid sequence, derived from a
      partial human cDNA, that fell within the second cross-kingdom lineage bears
      several characteristics expected for PGM2. A third lineage may contain homologs
      to human PGM3. On a general level, our phylogenetic-based approach shows promise
      for the further utilization of the extensive molecular database.

PMID- 9549098
TI  - Microsatellite conservation, polymorphism, and GC content in shrews of the genus
      Sorex (Insectivora, Mammalia)

PMID- 9549097
TI  - A hominoid-specific nuclear insertion of the mitochondrial D-loop: implications
      for reconstructing ancestral mitochondrial sequences.
AB  - A nuclear integration of a mitochondrial control region sequence on human
      chromosome 9 has been isolated. PCR analyses with primers specific for the
      respective insertion-flanking nuclear regions showed that the insertion took
      place on the lineage leading to Hominoidea (gibbon, orangutan, gorilla,
      chimpanzee, and human) after the Old World monkey-Hominoidea split. The sequences
      of the control region integrations were determined for humans, chimpanzees,
      gorillas, orangutans, and siamangs. These sequences were then used to construct
      phylogenetic trees with different methods, relating them with several hominoid,
      Old Work monkey, and New World monkey mitochondrial control region sequences.
      Applying maximum-likelihood, neighbor-joining, and parsimony algorithms, the
      insertion clade was attached to the branch leading to the hominoid mitochondrial
      sequences as expected from the PCR-determined presence/absence of this
      integration. An unexpected long branch leading to the internal node that connects
      all insertion sequences was observed for the different phylogeny reconstruction
      procedures. This finding is not totally compatible with the lower evolutionary
      rate in the nucleus than in the mitochondrial compartment. We determined the
      unambiguous substitutions on the branch leading to the most recent common
      ancestor (MRCA) of the mitochondrial inserts according to the parsimony
      criterium. We propose that they are unlikely to have been caused by damage of the
      transposing nucleic acid and that they are probably due to a change in the
      evolutionary mode after the transposition.

PMID- 9549099
TI  - Unusual observations in the histology of Pityriasis versicolor.
AB  - Histological studies were carried out on 25 patients with various morphological
      types of pityriasis vesicolor. In addition to the usual features, acanthosis
      nigricans-like picture in papular lesions, dilated blood vessels in erythematous
      lesions were observed. In sections stained with Periodic acid Schiff's stain
      (PAS) absence of granular layer in areas of close approximation of filaments to
      the stratum malpighii and presence of only mycelia in the vicinity of
      acrosyringium were found unusual, interesting and are new findings to our
      knowledge.

PMID- 9549100
TI  - Aspergillosis in German cockroach Blattella germanica (L.) (Blattoidea:
      Blattellidae).
AB  - Natural infection of Aspergillus flavus was observed in adults of Blattella
      germanica. Though the adult insects exhibited no external symptoms, they became
      hypoactive and later died. The dead and experimentally infected insects
      repeatedly yielded Aspergillus flavus in culture on Czapek's medium. Direct
      microscopic observation of the tissues of infected insects revealed fungal
      material. The blood films stained with Giemsa stain showed granulocytes (GRs)
      engulfing fungal hyphae. A remarkable increase in GR and plasmatocyte (PL) counts
      occurred in differential haemocyte counts (DHCs) of the infected insects. Two
      main types of immunological responses of the insect noticed were phagocytosis and
      encapsulation. DHC showed maximum involvement of GRs and PLs in immune mechanism.

PMID- 9549101
TI  - Humoral immune response to Malassezia furfur in patients with pityriasis
      versicolor and seborrheic dermatitis.
AB  - Humoral immune responses against exoantigen components of oval, elliptic and
      round yeast forms of Malassezia furfur were analysed by ELISA and Western
      blotting assays, using sera from patients with pityriasis versicolor (PV),
      seborrheic dermatitis (SD) and healthy adults (HA), as control. Sera from
      patients with SD showed IgG anti-oval M. furfur titers ranging from 1/400 to
      1/6400 showing geometric mean (GM) of 1/1472, higher than those obtained with
      sera from patients with PV (1/200 to 1/6400, GM = 1/1239). Both patient groups
      showed mean titres statistically superior (P < 0.05) than those obtained form HA
      (GM = 1/229). Similar data were also obtained with the elliptic and round
      antigens. However, the anti-oval IgG mean titers from patients' sera were much
      higher than those obtained with elliptic or round antigenic components (p < 0.05)
      Anti-M furfur IgM titers obtained from patient's sera with PV against all three
      exoantigens were statistically superior (p < 0.05) than HA group. Patients with
      SD showed IgM titers statistically superior (p < 0.05) only to oval yeasts of M.
      furfur. The IgA mean titers from patients' groups against the different
      morphological antigens were shown be slightly higher than those HA group. By
      Western blot, using rabbit anti-sera, the different antigenic components of
      M.furfur showed a close relationship mainly between oval and elliptic yeast cells
      antigens. The 70 kDa component of the M. furfur exoantigen of oval morphology was
      recognized by 84% of the PV patients' sera. On the other hand, SD patients' sera
      recognized 3 principal components of 70 kDa (100%), 65 kDa (67%) and 84 kDa
      (53%). These components may be considered immunological markers for PV and SD.
      Twenty-five percent of HA sera recognized the components of 65, 70 and 94 kDa.
      This investigation shows that M. furfur antigens can sensitize the host, mainly
      the oval yeast form of M. furfur with a very important specific IgG response in
      patients with SD and PV.

PMID- 9549102
TI  - Effects of dietary sugars and, saliva and serum on Candida bioflim formation on
      acrylic surfaces.
AB  - The effect of two dietary sugars, glucose and galactose, on biofilm formation of
      the oral fungal pathogen Candida on denture acrylic strips coated with saliva and
      serum pellicles was examined in vitro using Candida albicans (3 isolates), C.
      glabrata (2 isolates) and C. tropicalis (2 isolates). The degree of biofilm
      activity was affected by both the dietary sugar and the nature of the pellicle
      (ANOVA, p < 0.01). With most isolates the glucose grown yeasts demonstrated
      significantly more bioflim activity than the galactose grown fungi, in the
      presence of pellicles (ANOVA, p < 0.01 or P < 0.01). In contrast, one isolate of
      galactose-grown yeast elicited significantly higher biofilm activity than glucose
      grown yeasts on the control strips (ANOVA, p < 0.01). Taken together, these
      results imply that a saliva or a serum pellicle, and the carbon source in the
      environment, act a complex manner modulating Candida bioflim formation.

PMID- 9549103
TI  - Isolation of Cryptococcus neoformans from pigeon (Columbia livia droppings in
      northern Iran.
AB  - Nine hundred and eighty three specimens of pigeon droppings, collected in
      different regions of northern Iran, were examined. Of these samples, 175 (17.8%)
      were positive for Cryptococcus neoformans. All isolates obtained were C.
      neoformans var. neoformans. Most of these isolates of C. neoformans were from
      pigeon shelters. There were significant differences in isolation frequency
      between pigeon shelters and the other collection sites.

PMID- 9549104
TI  - Expression of carboxymethylcellulase on the surface of Escherichia coli using
      Pseudomonas syringae ice nucleation protein.
AB  - Ice-nucleation protein (INP), an outer membrane protein from Pseudomonas
      syringae, is able to catalyze the ice crystal formation of supercooled water. It
      was exploited for anchoring of Bacillus subtilis carboxymethylcellulase (CMCase)
      on the surface of Escherichia coli. A surface anchoring vector, pGINP21M, was
      created that contains the multicloning sites including BamHI, SmaI and EcoRI at
      the end of the 3' flanking region encoding the C-terminus of INP instead of the
      stop codon for subcloning the foreign genes. The CMCase gene was in-frame
      subcloned for making INP-CMCase fusion proteins. The ability of this vector for
      directing the actual synthesis of INP-CMCase fusion proteins was confirmed by
      Western blotting analysis. CMCase targeted on the surface of cells was verified
      by measuring whole cell CMCase activity and ice-nucleation activity. CMCase
      activity was mainly detected on the cell surface whereas no enzyme activity was
      detected in the culture supernatant. Ice-nucleation activity was also maintained
      even if an INP-CMCase hybrid was made. This means that the fusion protein is
      functionally expressed and has its biological conformation on the surface. INP
      CMCase fusion proteins were stable in the stationary phase. INP deleted of the
      repeating domain, thus producing no ice-nucleation activity, could also direct
      CMCase on the cell surface. This suggests that it has the secretion and targeting
      signal to the outer membrane.

PMID- 9549105
TI  - Characterization of galactosidases from Aspergillus niger: purification of a
      novel alpha-galactosidase activity.
AB  - An enzyme with beta-galactosidase activity and three proteins exhibiting alpha
      galactosidase activity were purified from a culture filtrate of Aspergillus niger
      grown on arabinoxylan. beta-galactosidase, optimally active at pH 4 and 60-65
      degrees C, was active against p-nitrophenyl-beta-D-galactopyranoside, lactose,
      and pectic galactan. It was not able to release galactose from sugar beet pectin
      or lemon pectin. Its action on pectic galactan was increased by the presence of
      beta-galactanase. The three forms of alpha-galactosidase activity that showed
      different molecular masses and pIs were found to have the same mass after
      deglycosylation with N-glycanase F and to be the same protein based on their N
      terminal amino acid sequence data. The purified alpha-galactosidase was shown to
      be different from alpha-galactosidase A from A. niger. This confirmed the
      existence of at least two different alpha-galactosidases in A. niger. alpha
      Galactosidase, optimally active at pH 4.5 and 50-55 degrees C, was active toward
      p-nitrophenyl-alpha-D-galactopyranoside, melibiose, raffinose, stachyose, and
      locust bean gum, on which substrate it exhibited synergism with beta-mannanase.

PMID- 9549106
TI  - [Prognosis-determining systems in medicine].

PMID- 9549107
TI  - [Rational distribution of resources in intensive medicine. Analysis of admission
      and discharge criteria at intensive care units].
AB  - Cost-containment in health care has become a major issue in today's practice of
      medicine. With its needs in advanced technologies and skilled personnel,
      intensive care is among the most expensive of all hospital activities. This fact
      makes the analysis of indications for intensive care unit admission, as well as
      early discharge, of paramount importance: patients who are not likely to benefit
      from intensive care are at the extremes of disease severity, since low-risk
      patients are not ill enough to need ICU admission and high-risk patients have a
      very high mortality, irrespective of intensive care treatment. In this paper we
      discuss, based on published evidence, the formulation of recommendations for
      admission and early discharge from ICUs, and also present the Society of Critical
      Care Medicine guidelines, on this subject.

PMID- 9549108
TI  - [Computerization of a clinical chemical laboratory. A contribution for quality
      assurance].
AB  - The application of computer science to the practice of laboratory medicine, one
      of the medical informatics fields, brings a complete revolution in laboratory
      work and the clinical pathologists profile. The authors explain the methodology
      for the implementation of such a system, in a perspective of quality assurance,
      defining the goals, objectives, customer requirements and analysis of the
      benefits they achieve. Finally the authors explain the future perspectives.

PMID- 9549109
TI  - [Prevalence of arterial hypertension in Cushing's syndrome].
AB  - OBJECTIVE: To determine the prevalence of hypertension (HT) in patients with
      Cushing's syndrome. PATIENTS AND METHODS: We studied 23 patients with Cushing's
      syndrome, 17 women (mean +/- SD age = 42.8 +/- 15.6 years) and 6 men (mean +/- SD
      age = 34.8 +/- 10.2 years). The etiologies were: 16-Cushing's disease, 3
      suprarenal adenoma, 2-suprarenal carcinoma and 2-iatrogenic. Blood pressure (BP)
      was measured at least three times and we consider hypertension when systolic BP >
      or = 140 mmHg and/or diastolic BP > or = 90 mmHg. RESULTS: The prevalence of HT,
      at diagnosis, was 73.9% (64.7% in women and 100% in men) and the mean BP was 163
      +/- 25/100 +/- 16 mmHg (158 +/- 26/97 +/- 15 mmHg in women and 182 +/- 5/114 +/-
      10 mmHg in men). From the 16 patients with Cushing's disease, 13 (81%) had HT;
      all the patients (n = 3) with suprarenal adenoma had HT; none with suprarenal
      carcinoma (n = 2) had HT and only 1 of the 2 patients with iatrogenic Cushing's
      syndrome had HT. After treatment, 14 patients entered remission, 6 persisted with
      active disease and 1 was missed during the follow-up. In the group of patients
      that entered remission, the prevalence of HT at diagnosis was 78.5% (n = 11),
      57.1% (n = 8) being after treatment. CONCLUSIONS: In this study, we found a high
      prevalence of HT at diagnosis (73.9%). After treatment and in the patients that
      entered remission, the prevalence of HT remained high (78.5% vs 57.1%). The high
      prevalence of HT in Cushing's syndrome, suggests its importance as a morbidity
      factor and also as an important diagnostic indicator, when present.

PMID- 9549111
TI  - [Relationships between basic sciences and medicine revisited].
AB  - 1. The role of basic research in medical institutions and in particular in
      Medical Schools is discussed. 2. Clinical practice is characterized, in its
      technical aspects, as a branch of biological technology. 3. It is suggested that
      the main functions of basic research practiced in medical institutions is to
      promote the interaction between physicians and scientists in other fields and to
      train physicians in the practices of other scientists. 4. It is suggested that
      the introduction of basic research in medical institutions implies: the
      recruitment of scientists from non-medical disciplines; a policy of funding that
      does not favour exclusively the clinical sector; the setting up of a regular
      graduate program, based on the scientifically active groups and adequately
      regulated.

PMID- 9549110
TI  - [Squamous cell carcinoma in individuals under 40 years of age].
AB  - We reviewed all the cases of Squamous Cell Carcinoma in people under 40 years of
      age, diagnosed histologically at the Dermatopathology Laboratory of the Santa
      Maria Hospital, from January 1985 to December 1993. The 19 cases detected were
      analysed for age, sex, occupation, anatomical site of the tumor, evolution, smoke
      and alcoholic habits, skin phototypes, immunosuppression, previous viral
      infections, previous radiotherapy or PUVA therapy and associated diseases. A
      prevalence of an occupation involving more exposure to the sun was found. Males
      were more affected than females (2.2/1). In 37% of the patients we detected heavy
      alcoholic habits. The most frequent anatomical site was the lower lip (42%).
      Patients with skin phototype I were more affected (53%).

PMID- 9549112
TI  - [Ethics, science and utilitarianism].
AB  - We begin this article with the distinction between Deontology, Moral and Ethics.
      We also review the concept and the relevance of Bioethics, as the "science of
      survival", and as part of Ethics, a section of Philosophy. We tried to answer two
      further questions considering the role of Science in orienting Ethics, or the
      possible place of utilitarianism in controlling Ethics. The author discusses some
      new aspects of the doctor/patient relationship, and their evolution in the last
      100 years, as well as the relations between patients and Health care
      institutions. Some ethical problems were also raised related to the beginning and
      the end of life. Finally the author reflects on the difficulties of defining
      ethical concepts in the near future.

PMID- 9549113
TI  - [Alcohol and free radicals. Various consequences: protein synthesis, endocrine
      disorders, immunity. Role of stress].
AB  - Ethanol is a powerful generator of oxygen free radicals, when metabolized in the
      liver or in other organs. Isoenzyme 2E1 of cytochrome P450 and aldehyde oxidase
      are the main mechanisms for the generation of these radicals. A consequence of
      free radical generation is a decrease in protein synthesis. As a result we have
      endocrine and immunity alterations. The paper ords with a brief discussion of
      stress associated to alcoholism.

PMID- 9549114
TI  - [Systemic effects of inhaled corticosteroids. Various pending questions].
AB  - Inhaled steroids play a central and undisputed role in the management of
      Bronchial Asthma, since inflammation has been recognised as the main
      physiopathological mechanism in this disease. Indeed, the earlier introduction of
      inhaled steroids in the therapy of Bronchial Asthma is currently being
      recommended by several authors. However, accompanying the much broader use of
      these drugs, concerns about the possibility of induction of adverse systemic
      effects have appeared more and more frequently in the medical community and in
      medical literature. This article addresses the main concerns related to the
      systemic effects of inhaled corticotherapy, critically reviewing the clinical
      significance of some of the more relevant published studies.

PMID- 9549115
TI  - [Latex anaphylaxis].
AB  - The authors present two case-reports of Latex Anaphylaxis--a rare but dangerous
      manifestation of latex allergy--, one in a patient belonging to a risk group and
      the other in a patient without previously identified risk factors. A review of
      latex allergy, and particularly of latex anaphylaxis, is made focusing on risk
      groups, aetiology, diagnosis, prevention and therapy. This paper also intends to
      draw attention to this health problem and stress the fact that it raises several
      medical and non-medical issues, requiring a multidisciplinary approach and
      discussion.

PMID- 9549116
TI  - [Adenocarcinoma of the Vater's ampulla associated with Von Recklinghausen's
      neurofibromatosis].
AB  - Von Recklinghausen's Neurofibromatosis is an autosomal dominant disease of
      variable manifestations. Association with gastrointestinal and hepatobiliary
      tumours is well documented, most of them being benign neurofibromas. Other
      tumours, such as leiomyomas, sarcomas, ganglioneuromas and carcinoids are less
      frequent. Much rarer is the development of epithelial malignancies and an
      ontogenic relation is not clear. The authors reports a case of adenocarcinoma of
      Vater's Ampulla and duodenal neurofibromas, in a patient with Von
      Recklinghausen's disease, presenting obstructive jaundice.

PMID- 9549117
TI  - [Hepatopulmonary syndrome].
AB  - Hepatopulmonary Syndrome is an uncommon clinical situation of unknown cause. It
      remains the focus of intense investigation and ongoing debate. The authors
      present a case of a 77 year old man with chronic liver disease known for 5 years,
      who developed central cyanoses, digital clubbing and hypoxemia. On searching for
      the cause of these clinical features, the diagnosis of Hepatopulmonary Syndrome
      was admitted and confirmed by contrast enhanced echocardiography using agitated
      saline, and also by technetium 99m-labelled macroaggregated albumin scanning.

PMID- 9549119
TI  - [Modified Body technique in the treatment of epithympanic cholesteatoma. Otologic
      group, Piacenza].
AB  - The Bondy technique is a particular radical, yet conservative, treatment where
      the intact tympanic-ossicular system is preserved during the operation. This
      technique was initially introduced by Gustave Bondy in 1910 and has been used at
      the authors' center since December 1983 with a few modifications. In the twelve
      years from December 1983 to December 1995 69 cases (66 patients) were treated
      with this technique: 5.6% of all chronic cholesteatomatose otitis surgically
      treated during that period. The following indications were applied: purely
      epitymapnic cholesteatoma, average transmission gap equal to or lower than 25 dB
      and intact bone chain. During the follow-up no signs of recurrent cholestatoma
      were found. The average post-operative transmission gap was greater than 25 dB in
      only 5 of the 54 cases with at least one year of follow-up. When used in selected
      cases, the modified Bondy technique can be considered an excellent option in the
      treatment of epitympanic cholesteatoma, making it possible to maintain the good
      pre-operative hearing without requiring a second operation.

PMID- 9549118
TI  - [Treatment of sudden hearing loss].
AB  - A total of 27 patients affected by sudden idiopathic deafness (SID) and 3 with
      sudden idiopathic anacousia (SIA) were treated within 10 days of onset of the
      disorder. The treatment consisted of intramuscular or per os administration of
      corticosteriods for 10 days and the simultaneous administration of carbogene for
      5 days. At the 5th day of corticosonic treatment, if audiometry did not reveal
      complete recovery, the treatment was associated for 7 days with Destrane 500 ml.
      The cases included neurosensorial deafness of 30 dB or more over at least 3
      adjacent frequencies and arising over a 12 hour period. Soft cord deafness was
      not included in the study. The following variables were analyzed: 1) patient age;
      2) extent of the hearing loss: average tone threshold for the frequencies of 500 
      1000-2000 Hz equal to or better than 70 dB HL (group A); tone threshold ranging
      between 71 and 89 dB HL (group B), tone threshold ranging from 90 to 110 dB HL
      (group C), anacousia (group D); 3) audiometric curve; 4) presence or lack of
      vertigo. After treatment 25 subjects (83%) indicated a recovery ranging from good
      to complete. It is significant that among this 83% there were 12 subjects, 9 with
      profound deafness and 3 with anacousia. The therapeutic association adopted made
      it possible to achieve two-fold activity: anti-edemagene and hemorheological. The
      most highly implicated etiology for SID was viral causing not only neural but
      also endothelial damage and leading to acute microcirculatory insufficiency.

PMID- 9549120
TI  - [Photocoagulation of the hypertrophic lower turbinates using ND:YAG laser:
      functional results].
AB  - The difficult nasal respiration due to hyperplastic hypertrophy of the turbinates
      is a broad topic of ongoing interest in otorhinolaryngology. The authors describe
      a study of 71 patients suffering from hyperplastic hypertrophy of the lower
      turbinates treated since 1994 by photocoagulation using a ND:YAG laser. The laser
      treatment was performed on an outpatient basis, under local anesthesia and
      assisted by the use of an Endo-Video Closed-Circuit Video-Camera. The authors
      explain the details of the procedure used, emphasize surgical precision and the
      numerous advantages, the scarcity of intra- and post-operative side effects, the
      lack of post-operative nasal plugging. In addition, they present the satisfactory
      functional results achieved. The patients treated were followed up for 6 months
      prior to surgery and 30 months after laser photocoagulation. After surgery the
      following tests were performed: fibroscopy, objective symptom evaluation,
      rhinomanometry, rhinometry, muco-ciliary transport time (MCT), IgAS assay and
      turbinate biopsy. The low cost of performing this procedure is certainly a plus.
      The results obtained show a significant and permanent improvement in nasal
      ventilation and this was both referred by the patients themselves and could be
      objectively revealed by the ongoing controls. In conclusion, photocoagulation
      using a ND:YAG laser is well accepted by both physician and patient. It can
      improve nasal ventilation while respecting the anatomic and functional integrity
      of the nasal fossae.

PMID- 9549121
TI  - [Genetics of laryngeal cancer: an experimental study].
AB  - Squamous cell laryngeal carcinoma accounts for 1% of all cancer deaths and 95% of
      all laryngeal malignancies. It is most frequently found in smokers over 40 years
      of age. This neoplasm is presently the object of cytogenetic studies in an
      attempt to identify a specific chromosome pattern. In a study of 29 cases of
      malignant primary laryngeal tumor, Nawroz (1993) found a loss of alleles in
      different loci mapped in the short arm of chromosome 9 (9p) in more than two
      thirds of the cases. In the same chromosome region, the loss of heterozygotes
      (LOH) was previously described in other neoplasms (leukemia, hematic tumors,
      melanomas). In an attempt to verify the predominant chromosome pattern and the
      loss of heterozygotes in chromosome 9, a cytogenetic, genetic-molecular study was
      performed on ten cases of laryngeal carcinoma. Among these subjects, two showed a
      hyperdiploid chromosome pattern (metaphase with more than 46 chromosomes per
      cell), five had a hypodiploid pattern (with less than 46 chromosomes per cell)
      while, for the remaining three cases, it was not possible to identify any
      metaphase. Numerous structural and numerical karyotype defects were found in
      chromosomes 1, 3, 4, 5, 9, 10, 13, 14, 16, 18, and Y. In 6 of the cases
      abnormality was found in chromosome 9 while in 10 it was apparently a homozygote.
      The study was performed with the use of fluorescent in situ hybridization (FISH)
      using a chromosome library specific for chromosome 9. A loss of the 9p segment
      could be found as a result of different types of alterations: deletion (case 1,
      2, 5, 7); non uniform transfer between chromosome 2 and chromosome 9 (case 2);
      other transfers involving the 9p segment (case 1, 4, 5, 7, 10). In six cases,
      analysis was further detailed at the molecular level by means of DNA
      amplification methods (PCR) and electrophoresis on denatured 10% polyacrylammide
      gels. LOH was studied using a polymorphic system specific for the short arm of
      chromosome 9. Four of the cases examined showed LOH for the system used while one
      case (case 4) gave no information. Case 9 did not show any loss of alleles. The
      present study suggests that the loss of a DNA sequence on chromosome 9p is
      primary to the neoplastic progression in laryngeal cancer.

PMID- 9549122
TI  - [Adhesion molecules in squamous cell carcinoma of the larynx: possible indication
      of prognosis].
AB  - Thirty patients with laryngeal tumors were divided into two groups on the basis
      of whether clinical and pathological features indicated good or bad prognosis.
      Samples of each tumor group were selected and examined by immunohistochemistry
      using mAbs, raised against integrin chains (beta 1, beta 4, alpha 2, alpha 3,
      alpha 6) and their ligands laminin 1 and 5, collagen type IV, two fibronectin
      isoforms (ED-A and ED-B) and two isoforms of tenascin known to be associated with
      neoplasm. Controls were provided by samples of tumor-free laryngeal mucosa
      removed during the surgical procedure. The normal topographical integrin pattern
      and the continuity of the basement membrane components was altered in both groups
      but the extent of these changes was significantly greater in those tumors with
      poor prognosis. Therefore, the groups could easily and reliably be distinguished
      by simply observing their immunohistochemical features. It is suggested that
      performing immunohistochemical analysis on biopsies may aid in early diagnosis as
      well as in adopting the proper therapeutic strategy to follow for these tumors.
      The above molecules may become one of the diagnostic tools available for head and
      neck surgical pathologists.

PMID- 9549123
TI  - [Study of phospholipid components in bronchoalveolar wash surfactants in
      laryngectomized patients].
AB  - Surfactants serve to keep the dimension of the lower airways normal. They
      regulate alveolar stability, guaranteeing uniform lung insufflation. In order to
      evaluate pulmonary surfactant modifications during chronic obstructive disorders
      of the airways, the phospholipid component in the surfactants was studied using
      the Broncho-Alveolar Wash (BAW). Ten subjects who had undergone laryngectomy and
      who were suffering from stable, chronic obstructive broncho-pneumopathy (COBP)
      with marked hypersecretion were studied along with a control group of 7 smokers
      showing no signs of COBP. As compared to the controls, the laryngectomy patients
      showed a statistically significant reduction in the total phospholipid content
      and a different concentration of some important phospholipid fractions. The
      laryngectomy patients showed varying degrees of COBP because of their previous
      smoking history: as in ex-smokers where a the "biochemical" damage induced by
      cigarette smoking is partially repaired. On the other hand, while in the group of
      smokers the damage, expressed as the total phospholipid content, was quite
      noteworthy (reduction in this content was up to 10 times that found in the non
      smoking subjects), the ex-smoking laryngectomy patients revealed less marked, yet
      still significant, damage.

PMID- 9549124
TI  - [Fronto-lateral laryngectomy using a combined endolaryngeal external approach].
AB  - Functional laryngectomies-whether subtotal (with significant demolition) or
      conservative (with limited latero-frontal and frontal demolition)-can, at times,
      lead to significant post operative functional sequelae. Negative outcomes method
      proposed calls for an internal, endolaryngeal approach along with an external
      approach. The internal approach makes it possible to carefully delimit the
      posterior extension of the laryngeal neoplasm. The external approach, on the
      other hand, makes it possible to remove the anterior commissure and part of one
      or both vocal cords in a single unit together with a smaller portion of the
      thyroid cartilage. In particular, the endolaryngeal approach using suspension
      microlaryngoscopy makes it possible to section the laryngeal structures all the
      way up to the internal surface of the thyroid cartilage and, anteriorly, along
      the midline from the incision to the lower edge of the cartilage. From above the
      larynx is opened by means of a transfixed section of the thyroid membrane and of
      the epiglottis at the upper edge of the thyroid cartilage. The ends of the
      section are joined with the upper ends of the section prepared using the
      endolaryngeal approach. Cranio-caudal dissection of the internal perichondrium of
      the thyroid larynx is then performed, from behind, all the way to the
      endolaryngeal sections and, from below, to the point where the cord ligaments are
      inserted. The larynx is opened from below by means of a horizontal section in the
      crico-thyroid membrane at the upper edge of the cricoid cartilage. The
      trapezoidal section of the lower part of the protruding corner of the thyroid
      cartilage. After having joined the edges of the crico-thyroid section with the
      lower edge of the endolaryngeal sections, the entire piece is then removed in a
      single unit. This method, for treatment of carcinoma of the anterior commissure
      and of the anterior portion of one or both vocal cords (T1 and T2 N0 M0), must be
      used after accurate clinical evaluation; it is particularly appropriate for
      subjects with cordo-commissure carcinoma which was previously treated with
      radiotherapy. The method meets the requirements of oncological radicalness,
      permits one to perform both the external and internal sections under visual
      control and maintains the endolaryngeal diameters nearly intact.

PMID- 9549125
TI  - [Biopsy of the temporal artery].
AB  - Horton temporal arteritis, or gigantocellular arteritis, is a panarteritis
      involving the mid-size and large arteries, in particular the temporal surface
      artery. This pathology is normally found in the elderly, particularly females. It
      can be manifest with some typical symptoms (i.e. cephalea, fever, visual
      disorders even leading to blindness mandibular claudication, high ESR, moderate
      anemia), there may be aspecific, atypical signs (i.e. only cephalea and fever, or
      widespread myalgia and artralgia) or it may arise following a cerebro-vascular
      accident. Treatment of this form of arteritis is based on the use of high doses
      of corticosteroids over a long period of time (at least 1-2 years). The present
      work describes a surgical technique for biopsying the temporal artery. The
      technique consists of withdrawal of a segment of the artery from the main branch
      and the frontal branch of the temporal surface artery. Since this form of
      arteritis often presents segmentary lesions, it is advisable to take a 4-5 cm
      sample so as to prevent false negatives. This simple surgical procedure can be
      performed under local anesthesia and is practically complication-free. The
      authors then discuss the indications for temporal artery biopsy and report 3
      clinical cases (case no. 1 is an example of the classical manifestation while
      cases no. 2 and 3 are atypical, aspecific forms). Since both the classical and
      atypical forms of gigantocellular arteritis require high doses of corticosteriods
      over a long period of time, the temporal artery biopsy procedure is highly useful
      in formulating an accurate diagnosis. The well known side effects to long-term
      cortisone use make it necessary to use all the available instruments in making
      the correct diagnosis. Bilateral biopsy can be performed in those cases where the
      first biopsy proved negative but gigantocellular arteritis is still suspected.

PMID- 9549126
TI  - [Pleomorphic adenoma of the lower turbinates: clinical case and review of
      literature].
AB  - A case of pleomorphic adenoma of the lower turbinate salivary glands is
      presented. A careful review of the literature has revealed that this is a highly
      unusual site for such neoplasms. The scarcity of symptoms is underlined as the
      lesion can long go unrecognized. Moreover, it is pointed out that, since only a
      small number of cases have thus far been presented for this benign lesion the
      prognostic factors indicating a clinical evolution to malignancy are as yet
      unknown. For this reason the authors feel it advisable to perform conservative
      surgery and carry out a careful follow-up.

PMID- 9549127
TI  - [Length of stay and diagnosis related groups (DRG) in otolaryngology in view of
      total quality management].

PMID- 9549128
TI  - [The first applications of radiotherapy in head and neck cancers].

PMID- 9549129
TI  - [Rendu-Osler disease: treatment with iridium 192].

PMID- 9549130
TI  - [Uniformed Requirements Manuscripts for biomedical journals (Vancouver
      Conference). International Committee of Editors of Medical Journals].

PMID- 9549132
TI  - [Response to sertraline in adolescents with obsessive-compulsive disorder].
AB  - Previous studies have revealed that serotonin reuptake inhibitors are effective
      for the treatment of obsessive compulsive disorder (OCD) in children and
      adolescents. The clinical efficacy of sertraline (STL) for eight adolescents with
      OCD is examined. The patients are between 12 and 17 years old, being 3 of them
      female and 6 male. The severity is measured with OC-NIMH Scale and self-report
      Leyton-20 questionnaire. Administration of STL was begun at 50-200 mg/day, with
      maintenance dose of 50-150 mg/day. Seven patients responded adequately to STL for
      more than six months; a girl, aged 16, require discontinuation of STL because of
      untoward effects. The improvement starts before the 8th week of treatment. Six
      months later improvement scores with OC-NIMH and Leyton-20 rated near the 50%. In
      the seven patients with STL either have no untoward effects or mild effect.
      Favorable results are observed either in adolescents who received STL and
      cognitive therapy or those with STL as main treatment without any structure
      psychotherapy. After 6-21 months with STL, improvement has continue of has been
      increased.

PMID- 9549131
TI  - [Limitations of the diagnosis of bipolar disorder].
AB  - INTRODUCTION: It has been studied the possible confusion in the diagnosis of
      bipolar disorder when there are no clear mania symptoms and other psychiatric
      disorders, due to his clinic similarity. The diagnosis received from a group of
      patients admitted in a Psychiatric Unit of a General Hospital by manic episode
      were studied. METHODS AND MATERIAL: 84 admitted patients have been followed up
      along an average of 32 months. By means logistic regression, there were found the
      factors that explained the change in the diagnosis along the evolution. RESULTS:
      87% of the patients after the follow up kept the diagnosis of bipolar disorder.
      However, 63.1% had received other diagnosis. Two factors predicted to receive
      other diagnosis: depressive clinic and not having stable couple. CONCLUSION:
      Bipolar disorder presents a proper stability once diagnosis have been made. It
      may be confused with psychotic sight, unipolar depression and B cluster
      personality disorders. It is checked that patients which start with manic
      psychosis phases are the ones that present biggest diagnosis stability.

PMID- 9549133
TI  - [Psychoeducative ambulatory group in bulimia nervosa. Evaluation of a short-term
      approach].
AB  - This study examined the relative efficacy of a brief-psychoeducational treatment
      approaches for bulimia nervosa. Our sample comprised 26 women who sought
      consecutively treatment at the Eating Disorders Outpatient Unit. All subjects met
      DSM-IV criteria for Bulimia nervosa. For the assessment were used commonly
      applied questionnaires in the fiel of eating disorders such as: Eating Attitudes
      Test (EAT-40), Eating Disorders Inventory (EDI) and the Beck Depression Inventory
      (BDI). Outcome measures included also change in vomiting and binge-eating
      episodes per week. Each patient was assessed before and after a 6 weeks brief
      psychoeducational group therapy. At posttreatment, 30% of the patients were
      abstinent from binge eating-purging and 62% reduced their weekly frequency in
      binge eating and 56% reduced their weekly frequency in vomiting. Good-outcome
      (EAT scores < 30) was observed in more than 35% of our patients. The authors
      sought to identify factors that differentiate bulimic patients who improve while
      receiving treatment from those who do not.

PMID- 9549134
TI  - [Reliability of the evaluation of regional cerebral blood flow using SPECT in
      chronic schizophrenia and bipolar disorder].
AB  - OBJECTS: Demonstrate the reliability of cerebral SPECT using 99 mTc-HMPAO.
      METHODS & MATERIALS: Evaluation of cerebral blood flow using SPECT in 24 patients
      with schizophrenia, 24 patients with bipolar disorder and 20 controls. In the
      study we have reliability between observers and intraobserver. In both cases
      kappa statistic has been applied for measuring reliability. RESULTS: reliability
      between observers represents a kappa coefficient of 0.71. Intraobserver
      reliability, with a medium grade concordance slightly superior, shows a medium
      kappa coefficient of 0.74. CONCLUSIONS: Visual evaluation of SPECT images using
      99mTc--HMPAO is a trustworthy technique to document the different patterns of
      regional cerebral blood flow. Reliability is determinate by the improvement,
      during visual analysis of reliability between observers (kappa: 0.71) and
      intraobservers (kappa: 0.74).

PMID- 9549135
TI  - [Smoking in a psychiatric population].
AB  - The relationship between tobacco consumption and psychiatric disorders is a
      widely discussed topic that is generating a considerable yet controversial
      bibliography, that can be approached from different points of view. The authors
      make a revision and critical evaluation about smoking prevalence on psychiatric
      population, in the different psychiatric disorders and discussing the theories
      implicated.

PMID- 9549136
TI  - [Naltrexone in the treatment of alcohol dependence].
AB  - This paper reviews preclinical research which demonstrates the involvement of the
      opioid system in the reinforcing effects of alcohol, and the effects of
      naltrexone, a long-acting, nonselective opioid receptor antagonist to reduce
      alcohol intake. Naltrexone (50 mg/day) may prevent the return to drinking by
      blocking the pleasurable effects or "high" associated with alcohol drinking, and
      relapse rates were reduced. The most common adverse effects reported include
      nausea and vomiting and it does not appear to be hepatotoxic in dosages
      recommend. Thus, naltrexone appears to offer significant therapeutic benefits,
      when used with behavioural treatment for alcohol dependent patients.

PMID- 9549138
TI  - [Bioavailability and bioequivalence. Studies in healthy volunteers].

PMID- 9549137
TI  - [Prescription of generic drugs].

PMID- 9549139
TI  - [Problems with generic drugs. Point of view of the pharmacist, the
      pharmacologist, and the clinician].

PMID- 9549140
TI  - [Physician battles in Spanish medicine of the 19th Century: from chaos to
      revolution].

PMID- 9549141
TI  - [Neurovegetative changes of the circadian rhythm in airline pilots in
      transmeridianal flights].

PMID- 9549142
TI  - [Artifact dermatosis].

PMID- 9549143
TI  - [Health care human values in current and future gynecology and obstetrics].

PMID- 9549144
TI  - [New commentaries on ataraxia y la asphaleia the security and domination of our
      self].

PMID- 9549145
TI  - [Tobacco/nicotine, habit or addiction?].

PMID- 9549146
TI  - [Lingual actinomycosis. A case report].

PMID- 9549147
TI  - [Esophageal achalasia and mongolism. Laryngeal papillomatosis and
      dermatomyositis. A common origin? Review].
AB  - Before the notorious increase of congenital malformations among individuals
      belonging to rurality, which are faced to yield between watering by sprinklers
      with weed-killers and the alarming growth of cardiovascular and pre--and
      malignant diseases we decided to undertake a perusal among the agents regarded
      since ever as bias toward to those pathologies. Following that conception we
      found out a common tendency between malnutrition, diabetes, alcoholism, drug
      addiction, weed-killers, and so on. The whole group generate energy reduction
      (ATP) starting from which appears a biochemical complex competent to give way to
      any cardiovascular pathology, autoimmune maladies or even congenital
      malformations.

PMID- 9549148
TI  - [In-depth study of the causes of sudden deafness. Physiopathological mechanisms
      and their reversal].
AB  - This article deals with an investigative work done by the AA. with the aim of
      determine the final cause of sudden sensorial deafness. Three causes are accepted
      as source of sudden deafness: viral infections, the tear away of labyrinthine
      membranes and the vascular theory. An increase in antibody titer suggest a viral
      origin. The labyrinthine membranes split has been observed at times when
      performing an exploratory tympanotomy. But circulatory troubles are hardly
      diagnosed, even with histopathological evidences of vascular upsets in temporal
      bones belonging to patients who suffered from an auditory stroke, because there
      are no diagnostic tests for "in vivo" control. Our intend is to investigate on
      the physiopathology of unforeseen deafness and also try to know the possible
      mechanisms of reversion of this calamitous pathology. We use, as investigative
      method of actual vascular changes in sudden deafness, the following; the speed
      analysis of the blood flow furnished by the A. labyrinthi through echography
      Doppler color transcranialis and angiography and magnetic resonance (Angio-MR).
      Both procedures are non invasive and harmless. We comment the findings of 13
      patients. And find out, in 4 cases, an important trouble of the arterial
      vertebrobasilaris flow. The A. labyrinthi, a branch of the A. cerebelli inferior
      anterior (ACIA) and/or A. basilaris--rarely from the A. cerebelli inferior
      posterior (ACIP)--showed a heavy hypoplasy of these vessels, stenosis or complete
      blockage. In 2 of cases, 4 months later, a new exploration of the Doppler flow
      and angio-MR, was performed, and detected an improvement of the vertebrobasilar
      flow, in both instances. In those patients with an evident recovery of the
      hearing, it was attributed to these two compensatory mechanisms: 1) reversal of
      the flow at the level of cicle of Willis, at the expense of development of A.
      communicans posterior, and 2) cessation of the vertebral A. spasm and decrease of
      the vessel's tortuosity so improving the blood flow.

PMID- 9549149
TI  - [Microbiological and auditory analysis before and after topical treatment of
      chronic suppurative otitis media without cholesteatoma].
AB  - The AA. present a study microbiologic and auditive as well about chronic,
      suppurative otitis media non cholesteatomatous, before and after topical
      treatment. They contemplate 178 samples of chronic discharging ears which were
      treated with gentamycin 0.3 %, instillation 5 drops every 8 hours, during 10
      days. Twelve days later were newly assessed both the otorrhea and the
      cochleovestibular picture. Germs most frequently detected: Gram-negative 61.6 %,
      Gram-positive 19.8 %, associated flora 6.4 % and mycosis 2.2 %, among other.
      Clinic healing accounted for 97.29 % and not significative differences scored pre
      -and post-treatment.

PMID- 9549150
TI  - [Pleomorphic adenoma as a parapharyngeal tumor. The role of the CT in
      differential diagnosis].
AB  - We described 2 cases of pleomorphic adenoma as parapharyngeal masses, one of the
      deep lobule of the parotid gland and the other one in palatine accessory salivary
      glands. After computed tomography (CAT) we made the anatomopathological diagnosis
      of pleomorphic adenoma with fine needle aspiration. We discuss about the role of
      CAT in diagnosis of pleomorphic adenoma occupying the parapharyngeal space.

PMID- 9549151
TI  - [The hamster's larynx as an experimental model].
AB  - A macroscopic study and with light microscopy as well is performed in the larynx
      of 4 hamsters. Morphology of hamster's larynx is described. Transitional
      epithelium is found out on the epiglottis base and caudally to the vocal cords.
      Hamster's larynx may be a good model for experimental study of changes during
      carcinogenesis.

PMID- 9549152
TI  - Bringing research to life.

PMID- 9549153
TI  - Anger and blood pressure readings in children.
AB  - This study investigated the relationship of state and trait anger measured by the
      Jacob's Pediatric Anger Scale, patterns of anger expression measured by Jacob's
      Pediatric Anger Expression Scale, and blood pressure readings (BPR) in 230 third
      grade children. Analysis of data revealed significant inverse relationships
      between anger suppression and diastolic BPR and anger reflection and control and
      both diastolic and systolic BPR. As anger suppression increased, diastolic BPR
      decreased. As anger reflection and control increased, both systolic and diastolic
      BPR decreased. When gender was considered, the relationship between anger
      reflection and control and systolic BPR was apparent only for girls, whereas the
      relationship between anger reflection and control and diastolic BPR was apparent
      only for boys. When correlations were computed based on gender and race, a
      significant inverse relationship between anger reflection and control and
      systolic BPR in Black girls was found. The results suggest that the influence of
      race and gender on the relationships between anger expression and systolic and
      diastolic BPR, which has been documented in adults, may be present in childhood.

PMID- 9549154
TI  - Humor and well-being in spouse caregivers of patients with Alzheimer's disease.
AB  - The relationship between the use of humor and well-being was studied in a
      convenience sample of 96 elderly spouse caregivers of community-residing patients
      with Alzheimer's disease (AD). Using hierarchical multiple regression analysis
      and controlling for severity of illness, caregiver education, and income, the use
      of humor accounted for 18.2% (p < .001) of variance in caregiver well-being.
      Caregivers of patients with advanced AD symptoms used less humor and had more
      psychological distress than those caregivers of patients who had mild symptoms.
      Because humor helps to maintain a sense of well-being, nurses should develop and
      encourage the use of humor in the spouse caregiver population.

PMID- 9549155
TI  - Living with osteoarthritis: insiders' views.
AB  - The purpose of this phenomenological study was to explore the day-to-day
      experiences of older people with symptomatic osteoarthritis (OA) and to discover
      if people in different socioeconomic strata differ in the ways in which they
      manage OA. Data were collected through semistructured interviews with 20
      respondents. The following four themes emerged from the data: refusing to give
      up, pragmatism toward treatment strategies, staying in charge, and tangible
      caring. Respondents more advantaged in socioeconomic status differed from less
      advantaged respondents in problems reported, treatments preferred, and causes of
      OA identified. Understanding the different ways people experience and live with
      OA and the importance of tailoring interventions to individual circumstances is
      essential to effective nursing management.

PMID- 9549156
TI  - Delirium: comparison of four predictive models in hospitalized critically ill
      elderly patients.
AB  - Delirium, a cognitive and behavioral disorder affecting more than one third of
      all hospitalized elderly patients, is often misdiagnosed or unrecognized by
      caregivers, leading to higher patient morbidity and mortality rates. Prediction
      of the disorder, based on known predisposing and precipitating risk factors, can
      be used to target susceptible patients for prevention and early intervention.
      Predictive models need to be evaluated for clinical application and predictive
      value. Therefore, in this study, four predictive models were applied on a case-by
      case basis to an elderly sample of 10 delirious patients and 10 nondelirious
      patients to determine sensitivity, specificity, and predictive values in a
      critical care setting. Results indicated six individual significant variables in
      these models: age, infection, dementia, blood urea nitrogen-to-creatinine ratio,
      severe illness, and comorbidity. A final multivariate model, derived from all
      variables, exhibited a sensitivity of 100% and specificity of 90% in predicting
      delirium in this study. Further studies are needed to substantiate these results.
      Then, identified risk factors can be incorporated into delirium prevention
      protocols for use by nurses at the bedside.

PMID- 9549157
TI  - Promoting adherence to an electronic home spirometry research program after lung
      transplantation.
AB  - Adherence with any long-term treatment or research protocol is a challenge; this
      has been found to be the case with lung transplant recipients participating in an
      electronic home spirometry research program. Because the purpose of the current
      study is to develop a system for detecting early infection and rejection in lung
      transplant recipients, regular transmission of data by subjects to the research
      data center is imperative to the success of the study. Various adherence
      promoting strategies have been developed by the research team to increase subject
      adherence with the program. An increased adherence rate has been reported after
      implementation of these various strategies, yet work remains to promote
      continually regular participation in the program by all subjects. It remains a
      challenge for the research team to devise creative and effective strategies for
      increasing adherence to regular spirometer use to provide data to develop a
      computerized system for detecting early infection and rejection of transplanted
      lung tissue.

PMID- 9549158
TI  - Promoting nursing research through newsletters.

PMID- 9549159
TI  - Nursing management structures: a research priority.

PMID- 9549160
TI  - [The role of trans-rectal echography (TRE) in the evaluation and staging of
      bladder tumors: comparison with suprapubic echography and computerized axial
      tomography (CAT)].
AB  - TAU and CT are, after cystoscopy, the two most largely used methods in the
      diagnosis and the staging of the bladder tumors. TRUS is mostly used in the
      pathologies of the prostate and the seminal vesicles. 38 patients (34 M and 4 F)
      suffering from bladder cancer are included in this study in the period from July
      1995 to January 1997. They are evaluated with TAU, TRUS and CT in order to
      evaluate the sensitivity and the specificity of TRUS in the diagnosis and the
      stadiation of bladder tumors. The patients included in this study are divided in
      two subgroups as patients having superficial and infiltrating tumors according to
      pathologic stage after TURB or radical cystoprostatectomy. Specificity and
      sensitivity values, overstaging and undestaging rates are calculated for each
      group. In the superficial tumors, TAU had a sensitivity and specificity of 72.2%,
      while with CT these values were respectively 70% and 75%; in the infiltrating
      tumors, TAU presented sensitivity of 65% and specificity of 70% while CT
      presented respectively 72.2% and 77.5%. With TRUS these values were 88.8% and
      94.4% in the superficial tumors and 90% and 95% in the infiltrating tumors. The
      method with the highest overstaging rate was CT with 33.3% while the ones with
      the highest understaging rates were TAU and CT with 22.2%. The sensitivity with
      TRUS was 100% in a total of 29 infiltrating and superficial tumors of the trigone
      while it was only 55.5% in the tumors of the lateral walls and the dome. With TAU
      these values were respectively 82.7% and 22.2%, with CT respectively 79.3% and
      44.4%. The specificity with TRUS was 100% for the tumors of the lateral walls and
      77.7% of the dome; with TAU these values were respectively 75.8% and 55.5% with
      CT 75.8% and 77.7%. In conclusion, TRUS may be used with a high sensitivity and
      specificity in the diagnosis and the stadiation of infiltrating and superficial
      bladder tumors situated at the peritrigonal zone and in the diagnosis of tumors
      situated in other regions of the bladder.

PMID- 9549161
TI  - Assessment of glomerular filtration rate by means of the three-compartment closed
      model after a single intravenous injection.
AB  - The two-compartment open model is currently used to assess glomerular filtration
      rate (GFR) with multiple blood samples. Numerous limited sampling models have
      been developed to reduce the number of blood samples. In the present study, the
      three-compartment closed model was used to assess GFR after a single intravenous
      injection. The three-compartment closed model includes blood, peripheral and
      urine compartments, thus the samples in urine can be used to estimate parts of
      pharmacokinetic parameters, thus to reduce the number of blood samples.
      Theoretically, the three-compartment closed model can assess GFR with one blood
      sample at any sampling time and three urine samples at any three sampling times.

PMID- 9549162
TI  - Coexistence of orbital and retroperitoneal involvement in multifocal
      fibrosclerosis: case report.
AB  - OBJECTIVE: To report a rare case of multifocal fibrosclerosis involving the
      retrobulbar tissue and the retroperitoneum. METHODS: A 59-year-old man presented
      with bilateral exophthalmos, more serious in the right eye. Right orbital biopsy
      showed fibrous tissue with inflammatory cells. After the failure of the radiation
      therapy, a right orbital exenteration was required. Radiological examinations
      demonstrated a retroperitoneal mass involving the perirenal fat, the aorta, the
      presacral and the perivesical tissue. Renal function impaired. A left inferior
      calycoureterostomy and a surgically placement of a right JJ stent were performed.
      Histological examination of the retroperitoneal biopsies revealed fibrous
      connective tissue. RESULTS: After 9 years of follow up, there was no change in
      left visual or renal function (last creatinine: 1.3 mg/dl), and no symptoms or
      signs of recurrences. CONCLUSION: This case is the ninth to document the
      association of orbital pseudotumor and retroperitoneal fibrosis. It is important
      that both the ophthalmologist and the urologist are aware of the existence of
      this association, so that suitable treatment can be initiated without delay.

PMID- 9549163
TI  - Ectopic adrenal tissue in the spermatic cord. Case report and review of the
      literature.
AB  - Ectopic adrenal tissue is a not uncommon clinical finding, especially in
      children. These aberrant rests have been reported in various locations, such as
      kidney, testis and related structures, female genital tract and
      supradiaphragmatic region. The most common site in the male genital district is
      the spermatic cord. We report a case of ectopic adrenal in the spermatic cord,
      occasionally found in an asymptomatic 42-years-old man. No other pathologic
      condition of urogenital tract was present. The nodule measured 0.5 cm in diameter
      and was histologically arranged in three well defined layers, with predominance
      of the zona fasciculata. No adrenal medullary tissue was observed. The
      pathogenesis of this ectopic tissue near the testis can be explained by the
      embryologic relationship between adrenal cortex and the gonad. Finally, we
      reviewed the relevant literature and the main clinical implications of this
      condition.

PMID- 9549164
TI  - Use of new automated biopsy device for percutaneous testicular biopsy. A
      preliminary clinical experience.
AB  - Testicular biopsy is indicated in the azoospermic patients to determine if the
      cause of azoospermia is ductal obstruction or testicular pathology and in certain
      patients who have severe oligozoospermia. The technique traditionally used is an
      open testicular biopsy. New Automated Biopsy Device has been used successfully
      for renal diseases. This instrument is now used by the urologist for transrectal
      prostate biopsy. The aim of this study was to evaluate whether percutaneous
      testicular needle biopsy with new automated device can replace open testis biopsy
      or not. 90 testes of 48 patients between 22 and 43 years olf underwent
      percutaneous testicular biopsy with a new 18-gauge automated biopsy device.
      Adequate samples were recovered from 90% cases (average 24.77 tubule sections per
      testis). When needle biopsy and open biopsy samples were compared in 30 testes of
      15 patients, complete agreement was obtained in 93%, whereas slight differences
      in 7%. These results show that percutaneous needle biopsy with new automated
      systems is cost-effective, quick, safe, repeatable, relatively painless and
      effective way to obtain largest possible cores through full cut technique. No
      serious complications were encountered during or after the procedure. The
      diagnosis were found to be comparable to those obtained by open biopsy. For these
      reasons, it is concluded that this new technique can replace the open biopsy.

PMID- 9549165
TI  - [Endoscopic treatment of bladder diverticula].
AB  - Since February 1993 six patients with bladder diverticula have undergone
      resection of the diverticular neck and fulguration of the diverticular mucosa at
      the time of transurethral resection of the prostate in 5 cases and urethral
      dilation in one case. The mean dimension of the diverticular was 5.2 cm. After a
      mean follow-up of 20 months the diverticulum has largely shrunk in one case and
      has completely disappeared in 5 cases. Our paper demonstrates the effectiveness
      of this technique in the treatment of bladder diverticular. In our opinion
      endoscopic fulguration represents a valid alternative to open surgery for the
      treatment of small bladder diverticular.

PMID- 9549166
TI  - [Laparoscopic unilateral retroperitoneal lymphadenectomy in non-seminomatous
      neoplasms of the testis in clinical stage I].
AB  - Since June 1993, unilateral laparoscopic retroperitoneal lymph node dissection
      (LRPLND) was performed in 6 patients diagnosed with clinical stage I
      nonseminomatous germ cell tumors (NSGCT). All of the patients had undergone prior
      radical orchiectomy. The testicular cancer was left-sided in three cases and
      right-sided in three cases. Preoperative staging by means of tumor markers
      assessment, computerized tomography scan (CT) of the chest and abdomen and chest
      X-ray was unremarkable for metastatic disease. All procedures were accomplished
      without any complications in a mean time of 325 min (275 to 420 min). The
      estimated peri- and postoperative blood loss was minimal. Of note, the comparison
      between the hematocrit and hemoglobin decrease of LRPLND and RPLND showed a
      statistically significant reduction (3.1 vs 11.1% P < 0.01 and 1.1 vs 3.2 g/dl P
      < 0.01). None of the patients required blood transfusion. In the case of the
      first patient the hospital stay was 18 days due to a widespread subcutaneous
      emphysema. In the remaining five cases the average hospitalization was 4.8 days
      ranging between 4 and 6 days. The patients resumed normal activities within 12 to
      27 days (mean 16.2 days) postoperatively. Mean number of lymph nodes removed was
      6.8, ranging between 5 and 9. Histologic examination of the dissected lymph nodes
      revealed microscopic metastases from embryonal carcinoma in two patients. Both of
      these patients were subject to adjuvant chemotherapy. The mean follow-up period
      is 33.3 months, ranging between 18 and 48 months. To date, no relapses have been
      observed. In accordance with other reports, we believe that LRPLND is both
      feasible and effective. However, larger and more comprehensive studies with long
      term follow-up are required to determine whether this approach is reliable and
      definitely superior to standard open surgery in the management of clinical stage
      I NSGCT.

PMID- 9549167
TI  - [Therapy of vasomotor syndrome in the treatment of advanced prostatic cancer:
      apropos of 37 cases].
AB  - Castration, whether surgical (orchiectomy) or pharmacological (androgen
      blockade), used in the management of advanced prostatic carcinoma, induces as a
      secondary effect, immediately following impotence, the onset of a vasomotor
      syndrome characterized by hot flushes and sweating. This syndrome which may
      present with such intensity and frequency as to severely affect the quality of
      life and even the psychological equilibrium of the patient. Treatment with
      progestinic agents leads to the release of opioid peptides at hypothalamic level,
      thus decreasing the level of catecholamines responsible for the vasomotor
      syndrome. In the 37 cases treated with progestogens, a therapeutic efficacy of
      80% was observed following cyproterone acetate and of 70% following
      medroxyprogesterone acetate.

PMID- 9549168
TI  - The early effects of doxazosin on benign prostatic hyperplasia.
AB  - It is known that selective alpha-1 adrenoceptor blockers diminish the symptoms
      and improve the uroflowmetric parameters in benign prostatic hyperplasia (BPH) by
      the effect on the dynamic component of BPH. The efficacy of doxazosin, a
      selective alpha-1 adrenoceptor blocker was evaluated in the treatment of BPH by
      assessing International Prostate Symptom Score (IPSS) and uroflowmetric
      parameters. While 24 patients were given doxazosin in a daily dose of 4 mg, 19
      patients were given placebo. Assessments of IPSS and uroflowmetric parameters
      were obtained three weekly periods. After three weeks, the decrease in IPSS was
      more prominent in doxazosin group when compared to placebo group (47% versus 12%
      respectively, p < 0.05) but improvement in the uroflowmetric parameters was not
      different statistically in the two groups (in Qmax 24% versus 16%, for doxazosin
      and placebo groups respectively, p > 0.05). After six weeks the improvement in
      IPSS continued and improvement in uroflowmetric parameters in doxazosin group was
      more evident when compared to placebo group (in Qmax 34% versus 19% respectively,
      p < 0.05). Objective results of doxazosin treatment in BPH can be observed after
      sixth week of the treatment although symptomatic effects can start at third week.

PMID- 9549169
TI  - Influenza activity in England and Wales remains low.

PMID- 9549170
TI  - Humanitarianism and local service institutions in Angola.
AB  - The role of local service institutions is not a major focus of current discourse
      on humanitarianism and complex emergencies. These institutions, in the few places
      where they are mentioned, are usually presented as either the seed of civil
      society and future democracy, or as pawns and components of the predatory
      economic, political and military elites. Few would deny that examples can be
      found which conform to both of these stereotypes. This simplistic representation
      of local institutions ignores the perspectives of the actors themselves--the
      nurses, extension agents, school teachers and others who actually staff most NGO
      supported projects. The debate has focused on what 'we' should do; the moral
      dilemmas of aid agencies and their expatriate staff, inevitably leading to the
      question of whether or not humanitarian workers should stay or leave situations
      in which aid may be causing more harm than good. Without denying the fundamental
      importance of these issues, it is important to consider also how the discourse
      has unfortunately moved away from those humanitarian workers who have no such
      choice, since they live there. Current concerns about keeping humanitarian aid
      from feeding local political and military struggles may inadvertently and
      paradoxically serve to constrain room for maneuver in the field, particularly
      among those individuals with the greatest tacit understanding of the predatory
      environment. There is a need to understand how actors in local service
      institutions make sense of their own situations, including the factors which
      frame their moral dilemmas and their day-to-day choices. By analysing the
      organisational processes within local service institutions, this study is
      intended to provoke consideration of how these individuals and their institutions
      may be effectively supported in complex emergencies through a focus on how they
      themselves deal with danger and complexity. It is suggested that there is a value
      in considering the lessons learnt in recent years about how service organisations
      in the North function in turbulent environments. This experience points to the
      importance of allowing workers the discretion to develop a relationship with
      their clients, and in so doing make sense of a confusing and ambivalent
      environment.

PMID- 9549171
TI  - The Northridge earthquake: community-based approaches to unmet recovery needs.
AB  - The 1994 Northridge, California earthquake has proven to be one of the most
      costly disasters in United States history. Federal and state assistance
      programmes received some 681,000 applications from victims for various forms of
      relief. In spite of the flow of US$11 billion in federal assistance into Los
      Angeles and Ventura counties, many victims have failed to obtain adequate relief.
      These unmet needs relate to the vulnerability of particular class and ethnic
      groups. In response to unmet needs, a number of non-governmental organisations
      (NGOs) have become involved in the recovery process. This paper, based on
      evidence collected from hundreds of in-depth interviews with the people involved,
      examines the activities of several community-based organisations (CBOs) and other
      NGOs as they have attempted to assist vulnerable people with unmet post-disaster
      needs. We discuss two small ethnically diverse communities in Ventura County, on
      the periphery of the Los Angeles metropolitan region. The earthquake and
      resultant disaster declaration provided an opportunity for local government and
      NGOs to acquire federal resources not normally available for economic
      development. At the same time the earthquake created political openings in which
      longer-term issues of community development could be addressed by various local
      stakeholders. A key issue in recovery has been the availability of affordable
      housing for those on low incomes, particularly Latinos, the elderly and farm
      workers. We discuss the successes and limitations of CBOs and NGOs as mechanisms
      for dealing with vulnerable populations, unmet needs and recovery issues in the
      two communities.

PMID- 9549172
TI  - Environmental information systems in malaria risk mapping and epidemic
      forecasting.
AB  - Every year between one and two million African children under five die of
      malaria. If one adds to this the contribution of malaria to all-cause infant
      mortality then clearly the burden of the disease is catastrophic--a disaster
      quietly happening each and every year. New tools are needed urgently to support
      those currently available for control of the disease. An effective vaccine
      remains elusive. This article outlines the potential contribution to malaria
      control services of satellite information, which is being used by resource
      managers in other sectors. In particular, it highlights the lessons which can be
      learned from early warning systems in other areas, especially those designed to
      respond to famine. An appendix provides a brief introduction to satellite data
      and their interpretation.

PMID- 9549174
TI  - Coping strategies in an ethnic minority group: the Aeta of Mount Pinatubo.
AB  - The particular problems arising in the aftermath of natural disasters in
      indigenous societies in the Third World, especially in ethnic or cultural
      minorities, have until now received only little attention in social scientific
      research. The potential of such indigenous groups to use their traditional
      knowledge and behaviour patterns in coping with natural disasters has been badly
      neglected. The example of the Aeta in Zambales, Philippines, a marginal group who
      were hit directly by the eruption of Mt Pinatubo in 1991, shows how traditional
      economic and social behaviour can in some measure determine their various
      survival strategies.

PMID- 9549173
TI  - Crop failure in Dalocha, Ethiopia: a participatory emergency response.
AB  - This case study of an NGO's response to a food crisis due to crop failure focuses
      on the extent of active community participation at each stage of the project.
      With the current debate on the relationship between relief and development, and
      in particular the focus on encouraging more active community participation in
      relief responses, this study has relevance both in the Ethiopian context and
      beyond. In this example the participation process was greatly facilitated by the
      prior relationship between the international NGO and the communities, and also by
      the high level of staff input into the project. Where resources or conditions are
      less favourable, as might be the case in similar responses by local NGOs or
      government agencies, the paper suggests that the participatory approach can be
      adapted or partially implemented and still result in a more effective and locally
      relevant operation.

PMID- 9549175
TI  - [Molecular physiopathology of Alzheimer's disease].

PMID- 9549176
TI  - [Infective endocarditis--a review of 21 cases in last 10 years].
AB  - Twenty one cases of infective endocarditis in last 10 years were re-evaluated by
      Duke's criteria. Fourteen strains of Streptococcus viridans, 4 of Enterococcus
      faecalis, 1 of Haemophilus parainfluenzae were isolated from blood culture. As to
      the minimum inhibitory concentration (MIC) of 8 strains of Streptococci, imipenem
      revealed the lowest MIC value, following penicillin G, ceftriaxon not equal to
      ampicillin, vancomycin and gentamicin. One strain of them was penicillin
      resistant (0.8 micrograms/ml). Serum inhibitory test (SIT) and serum bactericidal
      test (SBT) were undergone for 6 cases. The assay was efficient to determine
      penicillin-tolerance of causative bacterium. Vegetations were observed in 18
      cases of 21 by the echo-cardiography, especially transesophageal echocardiography
      had better diagnostic sensitivity compared to transthoracic echocardiography.
      However, it took 12 weeks from the first febrile episode to achieve definite
      diagnosis. One of reasons to take such a long time to reach diagnosis was that
      major causative organism was S. sanguis, whose inflammatory reaction to the host
      was said to be strikingly weak.

PMID- 9549177
TI  - Evaluation of increases in stature, upper extremity length and hand length in
      children from school age to the cessation of growth in Ogi County, Japan: a
      longitudinal study.
AB  - Stature, upper extremity length (UEL) and hand length (HL) were measured once
      yearly in children (171 males and 180 females) in Ogi County, Saga, Japan, from
      the 1 st grade of primary school (6.5 years of age) for 12 years. Based on the
      age of growth cessation, the order of growth cessation of stature, UEL and HL was
      investigated, in addition to the relationship between this order and the
      measurements obtained at 6.5 years of age. With regard to the order of growth
      cessation of stature and UEL, growth cessation of UEL occurred earlier than that
      of stature in 73.68% of males and 71.67% of females, growth cessation occurred
      simultaneously in 23.98% of males and 25.56% of females, and growth cessation of
      UEL occurred later than that of stature in 2.34% of males and 2.78% of females.
      According, growth cessation of UEL occurred earlier than that of stature in most
      subjects. In males, no significant differences were observed between subjects in
      whom growth cessation of UEL and HL occurred simultaneously and those in whom
      growth cessation of UEL occurred later than that of HL. However, in females,
      significant differences were noted, since the latter case was observed 1.69 times
      more frequently than the former. Nevertheless, growth cessation of stature, UEL
      and HL occurred at almost the same age in both males and females when cross
      sectional data was used for processing, in agreement with data reported by other
      researchers. We also investigated whether there was any relationship between
      stature and UEL at initial examination and the order of growth cessation. No
      significant relationship was observed. Each measured value at initial examination
      tended to be large in subjects in whom growth cessation of stature and UEL
      occurred earlier. In addition, final stature was significantly taller in both
      males and females in whom growth cessation of stature occurred later compared to
      those in whom growth cessation occurred earlier.

PMID- 9549178
TI  - A morphological study of the fetal ilium; focusing on the sexual differences of
      the greater sciatic notch.
AB  - A number of studies on sexual differences in the ilium have been reported.
      However, most of these studies have focused on the adult ilium. With regard to
      sexual differences in the fetal ilium, few studies have been carried out.
      Especially, there have few studies regarding sexual differences in the fetal
      ilium using dry bones. In the present study, sexual differences in the
      morphological characteristics of the greater sciatic notch were investigated
      using dry fetal iliac bones. We examined 212 fetuses (106 males and 106 females)
      measuring 20.0 cm or more in fetal length with free of gross malformations or
      deformities which were collected at Saga Medical School. The iliac bones were
      excised from these fetuses and dried as materials for study. Fetal length was
      measured in the fully extended position and was classified into six groups each
      for males and females in 5-cm increments, giving a total of twelve groups. The
      inner lateral surface of the greater sciatic notch was magnified 25x using
      projector, traced, and the tracings were inputted to a computer (7600/120: Apple
      Co. Ltd) using a flatbed scanner. The width and height of the greater sciatic
      notch were measured, as well as the area of the greater sciatic notch. No sexual
      differences were noted regarding the increase in the width of the greater sciatic
      notch in fetuses up to 39.9 cm in fetal length. In fetuses measuring between 40.0
      anf 44.9 cm, a significant sexual difference was observed, with the increase in
      greater sciatic notch width markedly greater in females. With respect to the
      increase in the height of the greater sciatic notch, no significant differences
      were noted. No significant differences were observed in the total area of the
      greater sciatic notch in fetuses up to 39.9 cm in fetal length. On the other
      hand, a significant sexual difference was observed in fetuses measuring 40.0 cm
      or more, with the total area markedly increased in females. In addition, no
      significant differences were found in the area between the two sides of the
      greater sciatic notch in fetuses up to 39.9 cm in fetal length, although
      significant differences were observed in fetuses measuring 40.0 cm or more. In
      female fetuses 40.0 cm or more in fetal length, the greater sciatic notch was
      found to be wider than in males, and the peak of the greater sciatic notch was
      displaced in the anteroinferior direction, farther from the auricular surface of
      the ilium and nearer the pubic bone. Thus these female fetuses show morphological
      characteristics of the adult female pelvic bone. Based on the results obtained,
      it is concluded that sexual differences can be identified in fetuses from the 8th
      month of pregnancy (fetal length 40.0 cm or more).

PMID- 9549179
TI  - Effects of p,p'-DDE on male reproductive organs in peripubertal Wistar rats
      following a single intraperitoneal injection.
AB  - The effects of p,p'-DDE on male reproductive organs were investigated in detail
      in peripubertal Wistar rats following a single intraperitoneal injection. 220
      mg/kg of p,p'-DDE (1/4 of LD50) were injected once into prepubertal and
      postpubertal Wistar rats and its effects were observed until 20 weeks of age.
      Weights of the body and reproductive organs in p,p'-DDE-injected rats were
      similar to those in control rats, who were injected with corn oil only. Sperm
      profile parameters such as spermatid number within the testis, sperm number
      within the epididymis, sperm motility and its morphology were not different
      between the prepubertal or postpubertal p,p'-DDE-exposed group and the control
      group. Like-wise, the histopathological examination at stage VII of the
      seminiferous epithelium cycle, when the germ cells are sensitive to testosterone,
      was similar in all three groups during the observation period. Serum levels of
      testosterone also showed no significant changes by exposure to p,p'-DDE under the
      conditions of this study. From these results, the antiandrogenic or estrogenic
      activity attributed to p,p'-DDE was not confirmed in male reproductive organs and
      no impairment of sperm profile was observed. This study confirmed that the
      reproductive functions of matured animals are scarcely affected by p,p'-DDE
      exposure during the peripubertal period and revealed that they might be
      relatively resistant to exogenous endocrine-disrupting chemicals. p,p'-DDE may
      threaten the hormonal equilibrium required for normal gonadal development during
      the organogenesis period, at an earlier stage of life. Further studies are
      necessary to fully reveal all the effects of p,p'-DDE on male reproductive organs
      and sperm profile.

PMID- 9549180
TI  - [Differences in the release of omeprazole in 4 commercial preparations: influence
      of pH and ionic concentration].
AB  - The influence of exposition to different ionic concentrations and pH values on
      the subsequent in vitro dissolution of omeprazole at pH 6.8 was studied in four
      enteric-coated commercial formulations. Assays were done using an experimental
      protocol similar to that recommended in Delayed-Release (Enteric Coated) Articles
      General Drug Release Standards (USP 23) slightly modified to achieve similar pH
      values to commonly observed in patients under omeprazole treatment. Omeprazole
      capsules were exposed during 1 or 2 hours to four different pH values: 4.8, 5.0,
      5.2, and 5.4 and two NaCl concentrations: 75 and 225 mM. After that, dissolution
      tests at pH 6.8 were performed. Three formulations (Emeproton, Pepticum and
      Ulceral) released different percents of the encapsulated dose at the above acidic
      mediums and, consequently, the omeprazole dissolved underwent a remarkable
      degradation. The drug contained in the enteric-coated granules of Losec was not
      released and therefore the amount of omeprazole dissolved at pH 6.8 from Losec
      capsules was higher than the obtained with the other three preparations tested.

PMID- 9549181
TI  - [Measurement of colonic transit time (total and segmental) with radiopaque
      markers. National reference values obtained in 192 healthy subjects. Spanish
      Group for the Study of Digestive Motility].
AB  - The interest for the technique of colonic transit time (CTT) measurement with
      radiopaque markers has been limited in our ambience, despite its documented
      clinical usefulness in evaluating patients with severe chronic idiopathic
      constipation. The aim of the present study was to contribute to the development
      of the technique by establishing the upper limit of CTT in a large series of
      healthy subjects in order to be used as national reference. Total and segmental
      CTT have been determined in 192 healthy subjects (114 men, 78 women; median age:
      33 yr; range: 18-88 yr) recruited in 18 hospitals of Spain. CTT measurement has
      been carried out by means of daily administration of 20 radiopaque markers during
      three consecutive days and plain abdominal X-ray taken at 4th, 7th and,
      eventually, 10th day. The upper limit (95th percentile) of total, right, left and
      rectosigmoid CTT was, respectively, 71.2, 22, 37.2 and 37.2 h. Women had
      significantly longer transits than men for whole (p = 0.002), right and
      rectosigmoid (p = 0.01, respectively) colon and near to statistical significance
      (p = 0.076) for left colon. In this series, CTT were not related to age and
      geographic area. Correlation between results obtained in the first reading of X
      ray done in each center and a second reading done by an independent observer, was
      excellent (p < 0.001). CTT measurement with radiopaque markers is a simple
      technique, attainable to different assistance settings. The obtained values are
      proposed as national reference given their independence from geographic area.
      When employing the technique to clinical evaluation of patients with
      constipation, the differences of CTT in function of gender should be kept in
      mind.

PMID- 9549182
TI  - [Malignant digestive tumor mortality in Castilla-La Mancha (1975-1990)].
AB  - BACKGROUND: The study investigates the temporary trend of the mortality by
      digestive malignant tumours in Castilla-La Mancha from 1975 to 1990. MATERIAL AND
      METHODS: Standardized rates were calculated by direct method, using world and
      european population as standard, truncated rates (35-64 years old) and cumulative
      rates (0-74 years old) according to tumoral location and sex. RESULTS: In both
      sexes the mortality by colon cancer has increased whereas the mortality by
      stomach cancer has decreased. These changes observed are similar with those
      observed in other epidemiologic studies. CONCLUSION: Driving a 15 year period a
      significant change in mortality due to colonic and gastric cancer has occurred in
      Castilla-La Mancha.

PMID- 9549183
TI  - [Seven-day omeprazole, clarithromycin, and amoxicillin for the therapy of
      Helicobacter pylori infection].
AB  - BACKGROUND: There are few series reporting efficacy of seven-day therapy with
      omeprazole, amoxicillin and clarithromycin for cure of Helicobacter pylori
      infection in Spain. The aim of the present study was to evaluate the efficacy of
      this treatment to eradicate H. pylori infection. PATIENTS AND METHODS: One
      hundred consecutive patients with peptic ulcer disease and H. pylori infection
      were evaluated for eradication therapy between January and November 1996. Four of
      them were excluded because of reported penicillin allergy. The remaining 96
      patients received a seven days course of omeprazole 20 mg/12h, clarithromycin 500
      mg/12h and amoxicillin 1 g/12h. The efficacy of the treatment was evaluated at 2
      4 months after therapy either by endoscopic biopsy or by 13C urea breath-test.
      RESULTS: Seventy-eight patients were found to be cured at the control evaluation.
      Intention to treat analysis showed a cure rate of 81.3% (95% CI: 74-89%). Per
      protocol analysis showed a cure rate of 85.7% (95% CI: 79-93%)--78 out of 91
      patient who returned for follow-up-. Compliance with the treatment was good in
      94.5% of patients. Five patients presented mild side effects (diarrhea, abdominal
      pain, oral candidiasis and metallic taste). None of them had to interrupt the
      treatment. CONCLUSION: Seven-day therapy with omeprazole, amoxicillin and
      clarithromycin achieves a 85% cure rate of H. pylori infection in our area.

PMID- 9549184
TI  - [Mesenteric lymph node cavitation: a rare complication of celiac disease in the
      adult].
AB  - A case of coeliac disease (CD) and mesenteric lymph node cavitation (MLNC) in a
      42-years-old female is presented. The other cases reported in the literature are
      also reviewed. The most important ganglionar histological features are described
      and a pathogenic explanation is suggested.

PMID- 9549185
TI  - [Arterioportal fistula and hemobilia in a patient with hepatic transplant].
AB  - The case of a 36-year old male liver transplant recipient hospitalized for upper
      digestive hemorrhage, jaundice and pain in the right hypochondrium is herein
      reported. Two hepatic biopsies had been performed 60 and 7 days prior to
      admission. Bleeding was observed to be from the biliary tract by endoscopy and an
      arterioportal fistula in the right hepatic lobe by echo-doppler and arteriography
      was seen. Treatment with selective embolization by arteriography was satisfactory
      with biliary tract drainage not being required. Doppler echography was used to
      control the evolution of the patient.

PMID- 9549186
TI  - [Malignant lymphoproliferative neoplasms and chronic hepatitis C virus
      infection].
AB  - It has been suggested that chronic hepatitis C virus (HCV) infection predisposes
      to the development of benign and malignant lymphoproliferative disorders. We
      present 2 cases of malignant lymphoproliferative neoplasias (a non-Hodgkin
      lymphoma [NHL] and a chronic lymphoid leukemia [CLL]) associated to chronic
      hepatitis C virus (HCV). The possible etiological role of HCV in the development
      of these tumors is discussed.

PMID- 9549187
TI  - [Acute hepatocellular lesion induced by amoxicillin-clavulanic acid].
AB  - Since first description in 1988, numerous cases of amoxycillin-clavulanic acid
      hepatotoxicity have been reported. Most of them are cholestatic hepatitis. A case
      of acute hepatocellular injury by amoxycillin-clavulanic acid is reported in a 23
      years-old male, with a favourable outcome after 18 weeks.

PMID- 9549188
TI  - [Cheap omeprazole?].

PMID- 9549189
TI  - [Drug hepatotoxicity: its prevention as an objective].

PMID- 9549190
TI  - [Choledochal cysts: physiopathology and treatment].

PMID- 9549191
TI  - [Computerized processing of endoscopic examinations: automation and
      digitalization].

PMID- 9549192
TI  - [Esophageal ulcer hemorrhage in HIV patient: treatment with argon laser].

PMID- 9549193
TI  - [Multiple biliary hamartomatosis: a multidisciplinary diagnosis].

PMID- 9549195
TI  - [New concepts on pathogenic mechanisms of Helicobacter pylori infection].

PMID- 9549196
TI  - [Influence of Helicobacter pylori and the host in the pathogenesis of peptic
      ulcer].

PMID- 9549197
TI  - [What role does gastric acid secretion play in Helicobacter pylori infection? A
      simple question with a complex response].

PMID- 9549198
TI  - [Gastric lesion caused by NSAID and inflammation due to Helicobacter pylori. Is
      there potentiation or attenuation?].

PMID- 9549199
TI  - [Helicobacter pylori infection and recurrent abdominal pain in children. A proved
      relationship?].

PMID- 9549200
TI  - [Indications for the eradication of Helicobacter pylori. Reflections on the
      Maastricht consensus conference].

PMID- 9549201
TI  - [Helicobacter pylori and gastric adenocarcinoma: definitely related?].

PMID- 9549202
TI  - [Helicobacter pylori and MALT-type gastric lymphoma: is it sufficient to
      eradicate the infection?].

PMID- 9549203
TI  - [Anti-Helicobacter vaccination: very far away or very close?].

PMID- 9549204
TI  - Nursing--a maturing discipline?

PMID- 9549205
TI  - The ties that bind.

PMID- 9549206
TI  - Consultation--opportunity or opportunism?

PMID- 9549207
TI  - Engaging in the policy dialogue.

PMID- 9549208
TI  - International nursing education: challenges and strategies for success.
AB  - The Nursing Education Partnership Program between Nell Hodgson Woodruff School of
      Nursing at Emory University and Foo Yin Junior College of Nursing and Medical
      Technology in Taiwan is in its third year. This program provides an opportunity
      for associate-degree nurses from Taiwan to earn a bachelor of science degree in
      nursing. The educational challenges, inherent in such a program, became evident
      early in the first semester. This article outlines those challenges and the
      educational strategies that were successful with this group. Implementation of
      the curriculum reflects four culturally significant aspects of the educational
      process: identifying community resources to meet basic needs for adaptation to a
      foreign country; redesigning teaching and learning strategies for international
      students; preparing faculty, clinical agency staff, patients, and other students
      to accept and become actively involved in this international program; and
      developing faculty-student relationships that promote mentoring and foster
      professional role development. Although the strategies presented were used with a
      group of students from Taiwan, they also can meet the needs of other
      international students.

PMID- 9549209
TI  - A prearranged mentorship program: can it work long distance?
AB  - Mentoring is a supportive and nurturing relationship between an expert and a
      novice. A formal mentorship program was embarked on by the Southern Council on
      Collegiate Education in Nursing during the early 1990s. The purpose of this
      article is to share the unique experience of two faculty who were assigned as
      mentors through a written inventory process and who were able to establish a
      successful mentorship, overcoming the barriers of time, distance, and an apparent
      mismatch of interests and clinical skills. The authors recommend mentoring as an
      important professional endeavor. Everyone-mentor, protege, and the nursing
      profession as a whole-gains during the mentoring process.

PMID- 9549210
TI  - The coming of age of military nursing research.
AB  - An Institute of Medicine (IOM) committee recently reviewed the TriService Nursing
      Research Program. In its report, The Program for Research in Military Nursing:
      Progress and Future Direction, the IOM committee ' supported the continuation of
      the program and made recommendations for improving it. The committee emphasized
      the importance of developing and supporting programs of research, establishing an
      environment of scientific excellence, determining areas for future research
      funding, and allocating resources for program infrastructure, management, and
      functions. This article expands that theme. It begins with an historical
      perspective; addresses challenges facing military nurse researchers and the role
      of programs of military nursing research; and offers a series of conclusions for
      leadership necessary to establish an environment of scientific excellence.

PMID- 9549211
TI  - Care: a value expressed in philosophies of nursing services.
AB  - Philosophies are written to reflect the values of the institution. Nursing
      service philosophies describe the essential features of nursing as practiced in a
      specific site. In this study, 10 philosophies of nursing services from community
      and teaching hospitals were content analyzed. Care emerged as a theme in each of
      the philosophies. The care construct was further categorized as general care,
      care approaches, and care descriptors: goal-directed, quality, safe, cost
      effective, effective, competent, and ethical. An exhaustive description of care
      as proposed by Colaizzi is presented.

PMID- 9549212
TI  - A centralized, computerized, and relational data base for student clinical
      placements.
AB  - Quality clinical experiences are a critical component of advanced practice
      nursing (APN) curricula. Historically, nursing instructors coordinated both the
      didactic and clinical components of a course. Increasingly, course coordinators
      organize the didactic component, and external preceptors working in the clinical
      setting function as practicum teachers. Both scenarios involve labor-intensive
      processes, and neither facilitate the scheduling of clinical experiences that
      build on progressive learning across the student's curriculum. A centralized,
      computerized, relational data base for efficient management of APN preceptors and
      students across the curriculum was designed. One master's-prepared clinical
      coordinator maintains the data base and performs all related functions. This
      system offers numerous benefits to students, preceptors, ] faculty, and nursing
      school, including balanced and progressively complex clinical learning
      experiences for students from competent preceptors: consistent interface with
      students and preceptors; faculty relief from time-consuming tasks; rapid
      generation of a variety of tables, rosters, and reports; consistent tracking of
      preceptor evaluations; timely acknowledgment of preceptor assistance; and
      efficient communication among students, preceptors, faculty, and school
      administration.

PMID- 9549213
TI  - A concept analysis of autonomy.
AB  - The nursing profession places a high value on the acquisition of autonomy as a
      requisite for professional status. Although the literature is replete with
      studies that examine autonomy and nurses, methods and results often are
      inconsistent and inconclusive. Review of the literature reveals ambiguous or
      absent definitions of autonomy. Nursing commonly confuses autonomy with related
      concepts such as authority, accountability, power, professionalism, and
      independence. A concept analysis of autonomy is done using Walker and Avant's
      modification of Wilson's analysis procedure. This highly abstract concept emerges
      as a discrete, empirically definable term referring to a potential human quality
      in an existing state. The analysis includes antecedents, consequences, defining
      attributes, model and borderline cases, and empirical referents.

PMID- 9549214
TI  - The changing self-concept of pregnant and parenting teens.
AB  - Self-concept has been recognized and researched as a powerful variable in
      relation to teenage pregnancy. Low self-concept frequently has been identified as
      a cause and consequence of teenage pregnancy as well as a factor in participation
      and compliance with health care recommendations. Most of the research on self
      concept and teenage pregnancy occurred in the 1970s to mid-1980s, and all found
      lower self-concept in pregnant and parenting teens when compared with their
      nonpregnant contemporaries and normative data. This study found the opposite to
      be true. The 126 pregnant and parenting teens in this study had higher self
      concepts than the reported normative group. Also, important variations in self
      concept were found in relation to sociodemographics. This potentially suggests
      that what was once known about this aggregate is no longer true, and a
      reinvestigation is warranted. The purpose of this study was to reinvestigate the
      self-concept of pregnant and parenting teens and compare them with published
      normative data and to examine the relationship between sociodemographics and self
      concept. The study employed a survey methodology. Data were analyzed using
      frequencies, percentages, measures of central tendency and dispersion, t test,
      chi-square test, and analysis of variance. This study found that pregnant and
      parenting teens had a higher self-concept than the normative data on nonpregnant
      teens reported by the research instrument authors. Furthermore, this older sample
      of pregnant and parenting teens (mean age, 17.83 years) had self-concepts more
      similar to the junior high school normative sample than their senior high school
      age contemporaries. Also, this study found that self-concept varies according to
      the pregnant and parenting teens; ages, years of schooling, types of schools
      attended, income sources, and receipt of public assistance. This study has
      implications for health care providers, health and public educators, and nursing
      researchers in terms of program development and evaluation, health marketing, and
      development of primary prevention strategies.

PMID- 9549215
TI  - Factors associated with National Council Licensure Examination-Registered Nurse
      success.
AB  - Identification of factors associated with National Council Licensure Examination
      Registered Nurse (NCLEX-RN) success is critical at public colleges of nursing
      with diverse student populations. This issue was the purpose of this research
      study. A descriptive correlational research design was used. Seventy-nine generic
      senior students enrolled in an urban public university participated in the study.
      Several internal and external blocks to success were described by the students,
      including family responsibilities, emotional distress, fatigue, and financial and
      work burdens. Significant correlations were found between success in the NCLEX-RN
      and cumulative undergraduate nursing program grade point average, English as the
      primary language spoken at home, lack of family responsibilities or demands, lack
      of emotional distress, and sense of competency in critical thinking.
      Establishment of a comprehensive data base-including factors associated with
      success in the NCLEX-RN and programs of advisement, tutoring, and stress
      management as well as classes in study skills, test taking, and NCLEX preparation
      are recommended for public colleges of nursing with diverse student populations.

PMID- 9549216
TI  - Education for nurses in administrative roles (supplement to the Essentials of
      Master's Education for Advanced Practice Nursing). American Association of
      Colleges of Nursing and American Organization of Nurse Executives.

PMID- 9549217
TI  - Wellmark to offer Medicare managed care products.

PMID- 9549218
TI  - IMS supports name-specific HIV reports.

PMID- 9549219
TI  - Is Medicare running out of time?

PMID- 9549220
TI  - Pharmacists take a shot at Medicaid reimbursement.

PMID- 9549221
TI  - A technological meltdown could be the end....

PMID- 9549222
TI  - The secret of low-load life insurance.

PMID- 9549223
TI  - Uwe E. Reinhardt, PhD.

PMID- 9549224
TI  - Bootstraps and jackknives: new, computer-intensive statistical tools that require
      no mathematical theories.

PMID- 9549225
TI  - Angiogenesis in rheumatoid arthritis: pathogenic and clinical significance.
AB  - In summary, angiogenesis, the formation of new blood vessels, is important in
      leukocyte extravasation and thus the pathogenesis of RA. The outcome of
      neovascularization highly depends on the imbalance between angiogenic and
      angiostatic mediators produced in the rheumatoid synovium. Therefore,
      angiogenesis research is important for the understanding of the pathogenesis of
      inflammatory arthritis. In addition, existing and potential angiostatic drugs may
      be useful for future therapy of RA.

PMID- 9549226
TI  - Simulated glomerular hypertension promotes mesangial cell apoptosis and
      expression of cathepsin-B and SGP-2.
AB  - BACKGROUND: Focal glomerulosclerosis (FGS) is characterized by the accumulation
      of mesangial matrix and lack of mesangial cells (MC). We studied the role of
      glomerular hypertension (GH) in the development of MC hypoplasia. METHODS: We
      used an in vitro model of GH to study the effect of GH on MC apoptosis. Cultured
      rat endothelial cells were grown in the intracapillary space and MCs were grown
      in the extracapillary space. MC proliferation as well as apoptosis was evaluated
      under simulated normal glomerular pressure (SNGP) as well as simulated glomerular
      hypertension (SGH). Apoptosis was determined morphologically by DNA fragmentation
      using Hoechst staining as well as with the use of DNA gel electrophoresis. MCs
      grown under SNGP and SGH were also evaluated for the expression of genes
      associated with active cell death. In addition, we evaluated the effect of direct
      applied pressure on MC apoptosis. RESULTS: MCs grown under SGH were less
      elliptical and had a tendency to develop a dome in the center. Direct applied
      pressure promoted MC apoptosis in a dose and time dependent manner. DNA gel
      electrophoresis from MCs grown under SGH also showed integer multiples of 180
      base pairs (ladder pattern); whereas cells grown under SNGP showed no DNA
      fragmentation. SGH increased mRNA expression of cathepsin-B (SNGP, 0.31 +/- 0.04
      vs SGH, 0.57 +/- 0.03, P < 0.01, n = 3) and SGP-2 (SNGP, 0.55 +/- 0.05 vs SHG,
      1.08 +/- 0.12, P < 0.01, n = 3) in MCs when compared to cells grown under SNGP.
      CONCLUSIONS: The present in vitro study suggests that GH has the potential to
      convert a hypercellular mesangium into a hypocellular one. This effect of GH is
      associated with expression of genes associated with active cell death.

PMID- 9549227
TI  - Enhanced lipid peroxidation in hepatic cirrhosis.
AB  - BACKGROUND: Lipid peroxidation is thought to play a role in the evolution of
      liver damage, based on evidence in experimental models. However, evidence that
      lipid peroxidation occurs in patients with liver disease remains to be provided.
      We addressed the hypothesis by measuring levels of 8-epi Prostaglandin F2 alpha a
      bioactive prostaglandin isomer produced by free radical catalyzed peroxidation of
      arachidonic acid, in patients with liver cirrhosis. METHODS: In 42 patients with
      hepatic cirrhosis 8-epi Prostaglandin F2 alpha, factor VII activity, endotoxemia,
      carotenoids and alpha-tocopherol were measured. In 10 patients 8-epi
      Prostaglandin F2 alpha was also measured before and 30 days after 300 mg b.i.d.
      vitamin E administration. RESULTS: Cirrhotic patients had significant higher 8
      epi Prostaglandin F2 alpha, excretion than controls [median (range): 199.2 (60.0
      812) vs 85.9 (55.6-160.0) pg/mg creatinine, p < 0.0001]. Patients with urinary 8
      epi Prostaglandin F2 alpha above the range in controls were more likely to have
      moderate or severe than mild liver failure (p < 0.004). They also had lower
      factor VII activity (62 +/- 19 vs 74 +/- 15%, P < 0.02) than patients with normal
      levels of the isoprostane. Urinary excretion of 8-epi Prostaglandin F2 alpha
      correlated directly with endotoxemia (Rho = 0.56, p < 0.0002) and inversely with
      factor VII (Rho = -0.39, p < 0.02). Cirrhotic patients given vitamin E showed a
      significant decrease of urinary 8-epi Prostaglandin F 2 alpha [median (range):
      342.5 (170 - 812) vs 292.5 (142-562) pg/mg creatinine, p < 0.04]. CONCLUSION:
      This study demonstrated that lipid peroxidation is increased in vivo in patients
      with cirrhosis and suggests that oxidant stress might contribute to the
      deterioration of liver disease.

PMID- 9549228
TI  - Lupus humoral autoimmunity induced in a primate model by short peptide
      immunization.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by humoral
      autoimmunity against the spliceosomal proteins, including Sm B/B'. In SLE
      patients with anti-Sm B/B' antibodies the proline rich sequence, PPPGMRPP, is the
      predominant Sm B/B' autoimmune epitope and appears to be an early target in the
      development of the anti-Sm B/B' response. METHODS: Two female baboons were
      immunized with the PPPGMRPP peptide from the Sm B/B' spliceosomal protein
      constructed on a MAP backbone in Freund's adjuvant. One female control baboon was
      immunized with Freund's adjuvant alone. Baboon sera were collected and assessed
      for antibody binding to the spliceosomal proteins and compared to SLE patient and
      control sera. RESULTS: Peptide immunized baboons developed antibodies to multiple
      regions of the Sm B/B' protein, as well as reactivity against other spliceosomal
      proteins. Consistent with serologic manifestations found in SLE, experimental
      baboons also acquired anti-nuclear antibodies, anti-nuclear ribonucleoprotein
      (nRNP) antibodies and, in one animal, anti-double stranded DNA antibodies. The
      control animal had none of these immunologic findings. CONCLUSIONS: Immunization
      with PPPGMRPP is capable of initiating a humoral autoimmune response in primates
      against the Sm, nRNP complex from which the peptide was derived. The additional
      autoantibody specificities generated in experimental animals are similar to those
      found in human SLE sera. This study is the first evidence of peptide induction of
      SLE humoral autoimmunity in a primate model.

PMID- 9549229
TI  - Elevated carcinoembryonic antigen in patients with androgen-independent prostate
      cancer.
AB  - BACKGROUND: Extraordinarily high serum carcinoembryonic antigen (CEA) values have
      been reported to be associated with many malignant disorders, including carcinoma
      with primary sites in the colon, pancreas, stomach, bile duct, lung, and breast.
      This study was undertaken to determine if a marked elevation of serum CEA levels
      in androgen-independent prostate cancer patients exists, and to evaluate the
      potential of using CEA monitoring as a marker for disease progression. METHODS:
      Records from 141 patients with progressive androgen-independent prostate cancer
      who were treated at the National Cancer Institute from 1990 to 1996 were
      analyzed. Serum CEA concentrations were measured using a micro-particle enzyme
      immunoassay. RESULTS: Among these cases of prostatic carcinoma, 69 (48.9%) had
      abnormally elevated plasma CEA values (greater than the normal upper limit of 2.5
      ng/mL) at some time during their treatment on a clinical investigation protocol.
      No correlation was found between the elevated CEA concentrations and prostate
      specific antigen (PSA). In comparison, 32.5% of patients with elevated CEAs had
      disease that had metastasized to soft tissue (adenopathy, etc) versus 22.2% with
      normal CEA who had soft tissue involvement (p = 0.3 X2). We examined the CEA
      values with respect to survival time, defined as the interval from the date of
      the earliest CEA level to the date of death and found no association (p > 0.3).
      CONCLUSIONS: Based on these observations, it appears that in the context of
      androgen-independent prostate cancer, CEA can be elevated but is an inviable
      surrogate marker of disease progression with minimal prognostic value.

PMID- 9549230
TI  - Rapid differentiation of Mycobacterium tuberculosis and Mycobacterium bovis using
      glycerol susceptibility and quantitative polymerase chain reaction.
AB  - BACKGROUND: The differentiation between Mycobacterium tuberculosis (MTB) and
      Mycobacterium bovis has significant epidemiological and therapeutic implications,
      such as their susceptibility to different drugs and the need for different
      approaches to patient isolation. However, currently this differentiation is based
      on laboratory methods that take 8 to 16 weeks. Simple qualitative polymerase
      chain reaction (PCR) can not differentiate between MTB and M bovis because of
      their genetic similarities. METHODS: We evaluated the use of quantitative PCR
      (QPCR) and glycerol susceptibility to differentiate MTB from M bovis. Three
      patient isolates of M bovis and 5 patient isolates of MTB were suspended in 7H9
      broth containing 0.0%, 0.2%, or 0.6% glycerol. These suspensions were inoculated
      on 7H11 plates and incubated at 37 degrees C and 5% CO2. QPCR was performed after
      0, 3, and 6 days of incubation. RESULTS: After 6 days of incubation for M bovis
      isolates, the mean DNA concentration decreased by one log in the presence of 0.6%
      glycerol while for MTB isolates, the mean DNA concentration increased by one log
      regardless of the glycerol concentration. CONCLUSION: These data suggest that
      QPCR and glycerol susceptibility may be used to differentiate between MTB and M
      bovis within 1 week.

PMID- 9549231
TI  - Effects of diabetes and difluoromethylornithine treatment on hyperplasia,
      activity of MAP-kinase, and activity and association with cyclin B of p34cdc2
      kinase in rat jejunal mucosa.
AB  - BACKGROUND: The different signal transduction pathways of rapidly proliferating
      cells of the intestine are not clearly understood. We report here a possible
      signaling pathway that involves regulation of activity of two closely related
      kinases, MAP-K (mitogen-activated protein kinase) and p34cdc2 kinase, during
      hyperplasia of diabetic jejunal mucosa. Our aim was to investigate the activity
      and phosphorylation of MAP-K and activity and association of p34cdc2 kinase with
      cyclin B during diabetes-induced jejunal mucosal hyperplasia in vivo. METHODS: We
      studied untreated and difluoromethylornithine (DFMO) treated control rats and
      rats with streptozotocin-induced type I diabetes. Assays were done 10 days after
      the induction of diabetes. In diabetic rats there was jejunal hyperplasia as
      indicated by increases in the jejunal mucosal weight/cm and DNA content as well
      as increased activities of MAP-K and p34cdc2 kinase and association of the latter
      with cyclin B as compared to corresponding values in control rats. Administration
      of DFMO, an irreversible inhibitor of the proliferation-associated enzyme
      ornithine decarboxylase (ODC), prevented diabetes-I induced jejunal hyperplasia
      and decreased all of the above enzymic parameters in both diabetic and control
      rats. In our previous in vivo study, DFMO administration also blocked diabetic
      jejunal hyperplasia and in addition decreased ornithine decarboxylase and
      tyrosine kinase activities jejunal and tyrosine phosphorylation of proteins.
      CONCLUSION: Thus the jejunal mucosal hyperplasia found in diabetes appears to
      involve activation of signal transduction pathways involving tyrosine kinases,
      MAP-K, p34cdc2 kinase, and cyclin B.

PMID- 9549233
TI  - Special issue on human behavioral genetics: synthesis of quantitative and
      molecular approaches.

PMID- 9549232
TI  - NADH-methemoglobin reductase (cytochrome b5 reductase) levels in two groups of
      American blacks and whites.
AB  - BACKGROUND: Sickle cell trait, glucose-6-phosphate dehydrogenase (G6PD)
      deficiency and alpha-thalassemia trait are common genetic abnormalities among the
      American Black population. Under oxidative stress, the presence of any of these
      conditions would predispose the hemoglobin (Hb) to oxidation resulting in
      accelerated methemoglobin (metHb) formation. It was hypothesized that red cells
      phenotypic for these genetic variants should have more or different levels of
      metHb reductase (cytochrome b5 reductase) activity. METHODS: To test this
      hypothesis, we measured the red cell metHb reductase activity in 558 male
      subjects (316 Blacks and 242 Whites), by the procedure described by Beutler. All
      Black patients also had G6PD spot test and Hb electrophoresis. In addition, all
      patients had a complete blood count (CBC). If the hematocrit was < 35% a
      reticulocyte count was also done. Patients with corrected reticulocyte (retic
      count X hematocrit/45) index over 2% were excluded regardless of other findings.
      RESULTS: The results showed that Blacks had different metHb reductase activity
      levels than Whites (mean = 3.19 vs 2.89 IU/gHb, respectively with p = 0.03).
      However, the differences in metHb reductase activities in patients with sickle
      cell trait, G6PD deficiency, and low MCV < 80 micron3 (presumptively having alpha
      thalassemia) in small subgroups did not reach statistical significance (p = 0.2),
      although, all 3 groups were comprised of small numbers. CONCLUSIONS: It is
      concluded that American Blacks have significantly different metHb reductase
      activity. The different metHb reductase activity in Blacks seems to be unrelated
      to the presence of G6PD deficiency, sickle cell trait, or alpha-thalassemia and
      it may be the result of genetic polymorphism. However, our study samples do not
      exactly represent the cross-sections of the Black and White populations. In
      addition, all patients were male in this study. Therefore, this study should be
      confirmed using larger and more population-representative samples. The clinical
      significance of this problem is not clear at this time.

PMID- 9549234
TI  - Behavioral genetics and evolutionary psychology: unified perspective on
      personality research.
AB  - Behavioral geneticists and evolutionary psychologists have generally pursued
      human behavioral analyses with little theoretical or methodological exchange.
      However, significant benefits might accrue from increased communication between
      these disciplines. The primary goals of this article are (1) to identify
      meaningful junctures between behavioral genetics and evolutionary psychology, (2)
      to describe behavioral genetic research designs and their applications to
      evolutionary analyses, and (3) to reassess current personality research in light
      of behavioral genetic and evolutionary concepts and techniques. The five-factor
      model of personality is conceptualized as subsuming variation in normative
      species-typical systems with adaptive functions in the human environment of
      evolutionary adaptation. Considered as universal evolved mechanisms, personality
      systems are often seen in dynamic conflict within individuals and as highly
      compartmentalized in their functioning between settings. However, genetically
      influenced individual differences in personality may also be understood within an
      evolutionary framework. Studies of the heritability of personality traits
      indicate broad-sense heritabilities in the 0.40-0.50 range with evidence of
      substantial nonadditive genetic variation and nonshared environmental influences.
      Evidence indicates that evolutionary theory (e.g., inclusive fitness theory)
      predicts patterns of social interaction (e.g., cooperation and bereavement) in
      relatives. Furthermore, variation in personality may constitute a range of viable
      strategies matching the opportunities available in the complex niche environment
      of human societies. Within this wide range of viable strategies, personality
      variation functions as a resource environment for individuals in the sense that
      personality variation is evaluated according to the interests of the evaluator
      (e.g., friendships, coalitions, or mate choice).

PMID- 9549235
TI  - Functional organization of the human mind: implications for behavioral genetics
      research.
AB  - It is proposed that the fundamental goal of human behavior is to organize and
      control the social, biological, and physical environments that support
      reproduction and survival and that the human mind is organized as a system of
      social, biological, and physical modules that support attempts to seek such
      control. More precisely, modules are systems of motivational, emotional,
      cognitive, and behavioral processes that provide the interface between this
      fundamental goal and the environments within which this goal must be achieved. An
      outline of this functional systems approach to the human mind is provided and the
      implications of this perspective for behavioral genetics research are discussed.

PMID- 9549236
TI  - Innateness, evolution, and genetics of language.
AB  - Our goal in this article is to review a debate over the evolution of language and
      to suggest some keys to its resolution. We begin with a review of some of the
      theoretical and empirical evidence for the innateness of language that has caused
      renewed interest in the evolution of language. In a second section we review some
      prominent theories of the evolution of language, focusing on the controversy over
      whether language could have been adapted for some purpose. We argue that for
      evolutionary studies of language to advance, theorists must make more persuasive
      arguments for the purpose of language, and, furthermore, linguists must continue
      to develop a detailed theory of syntax. Finally, we suggest ways that behavioral
      and population genetics could help to inform studies of the evolution of
      language.

PMID- 9549238
TI  - Molecular approaches to the genetic analysis of specific reading disability.
AB  - Specific reading disability is a complex phenotype that is under both genetic and
      environmental influences. There is evidence for at least one major gene, which
      may be detectable by parametric linkage analysis, but detection of other
      quantitative trait loci may require nonparametric methods. Phenotype definition
      may also be critical in identifying genes that affect different components of the
      reading process. Current research from two separate laboratories supports the
      localization of one gene influencing reading disability to the histocompatibility
      region of chromosome 6p and suggests that another gene may be located on
      chromosome 15. Actual identification of these and similar genes is complicated by
      reduced penetrance and phenocopies in families, so that delineation of the
      critical region using crossover analysis is problematic. This difficulty can
      result in the identification of many candidate genes that need to be evaluated
      through combinations of association analysis, functional analysis, and mutation
      assays.

PMID- 9549237
TI  - Multivariate behavioral genetic analysis of achievement and cognitive measures in
      reading-disabled and control twin pairs.
AB  - In recent years behavioral genetic studies have provided conclusive evidence that
      reading disability and related learning disorders, such as mathematics
      disability, are due at least in part to heritable factors (DeFries et al. 1987;
      Alarcon et al. 1997). Although the observed relationship between performance in
      these areas also may be due substantially to genetic influences (Light and
      DeFries 1995; Thompson et al. 1991), relatively few studies have examined the
      genetic and environmental etiology of this covariation in a multivariate
      framework. In the present study data from 196 identical (monozygotic; MZ) and 155
      same-sex fraternal (dizygotic; DZ) twin pairs in which at least one member of
      each pair evidenced reading problems in school (reading disabled) were subjected
      to a multivariate behavioral genetic analysis. Structural equation models were
      fitted to twin data for verbal IQ (VIQ), phonological decoding ability (PHON),
      reading performance (READ), and mathematics performance (MATH) to assess the
      extent to which VIQ and PHON mediate the observed covariation between READ and
      MATH. Results suggest that VIQ and PHON account for most of the covariation
      between READ and MATH. Moreover, approximately 82% of the observed correlation
      between READ and MATH was due to genetic factors that also influence VIQ and
      PHON. When data from 132 MZ and 91 same-sex DZ control twin pairs in which
      neither twin had a history of reading problems were subjected to the same
      analyses, the covariation between READ and MATH was found to be due to both
      genetic and shared environmental influences. Thus genetic factors that influence
      VIQ and PHON also contribute to the observed covariation between READ and MATH in
      both a reading-disabled and a control twin sample.

PMID- 9549239
TI  - Genetic and environmental influences on adult intelligence and special mental
      abilities.
AB  - I review representative biometric studies of adult twins and adoptees that have
      been used to generate estimates of genetic and environmental influence on
      intelligence (IQ) and special mental abilities. The various studies converge on a
      heritability estimate between 0.60 and 0.80 for IQ. Estimates of common
      environmental influence from the same studies are near zero. Studies of twins
      reared together and studies of unrelated individuals reared together yield
      sizable estimates of common family environmental influence in childhood but also
      demonstrate that this influence dissipates with age and approaches zero in
      adulthood. Twin studies of the major special mental abilities (verbal, spatial,
      perceptual speed and accuracy, memory) yield heritability estimates of about 0.50
      and modest estimates of common environmental influence.

PMID- 9549240
TI  - Molecular genetic studies of cognitive ability.
AB  - Given that the evidence of a substantial genetic contribution to cognitive
      ability is now convincing, the next challenge is to locate and identify the genes
      involved. It is likely that there are several genes, each of only small effect.
      Detection of such so-called quantitative trait loci contributing to polygenic
      traits in plants and animals is facilitated by the ability to carry out
      experimental crosses. However, in humans detection of quantitative trait loci
      depends on studies of siblings or other relative pairs or on allelic association
      studies aimed at detecting linkage disequilibrium in populations. The allelic
      association approach is currently being applied to investigate cognitive ability
      by using both candidate genes and DNA pooling methods that potentially allow
      rapid screening of the whole genome for quantitative trait loci.

PMID- 9549241
TI  - Genetics of spoken language disorders.
AB  - If language is the result of specialized structures in the brain and if these
      language-specific structures are genetically encoded, one would expect to find
      evidence of the heritability of language. In this article I review the results of
      family aggregation, pedigree, sex ratio, commingling, and segregation studies of
      spoken language disorders. The results of these studies provide evidence that,
      although spoken language disorders are genetically and behaviorally
      heterogeneous, genetic factors may play a substantial role in many cases of
      developmental spoken language disorders.

PMID- 9549242
TI  - Molecular genetic approaches to the study of language.
AB  - The application of the techniques of modern molecular biology to the study of the
      genetic control of language development poses many significant challenges.
      Because language is a complex function, disruption of any of a number of systems
      can impair language development. The diagnostic classification of specific
      language impairment includes individuals with an apparently inherited form of
      disordered language development, and therefore some aspects of this clinical
      phenotype may be useful for positional cloning studies of genes related to
      language. Known genetic disorders with specific deficits in language functions
      may also serve to identify candidate genes for language development. In addition
      to these specific approaches, the current general strategies for positional
      cloning and candidate gene studies are reviewed.

PMID- 9549243
TI  - Human sexual orientation has a heritable component.
AB  - We present an overview of behavioral genetics research on homosexual and
      heterosexual orientation. Family, twin, and adoptee studies indicate that
      homosexuality and thus heterosexuality run in families. Sibling, twin, and
      adoptee concordance rates are compatible with the hypothesis that genes account
      for at least half of the variance in sexual orientation. We note observations of
      homosexual behavior in animal species, but the analogy to human sexual
      orientation is unclear. We discuss the reproductive disadvantage of a homosexual
      orientation and present possible mechanisms that could maintain a balanced
      polymorphism in human populations.

PMID- 9549244
TI  - Molecular investigations into complex behavior: lessons from sexual orientation
      studies.
AB  - A review of recent molecular genetic investigations into sexual orientation is
      presented and used as a model to identify unique challenges encountered in
      research on complex behavior. Five main themes are presented that are generally
      applicable to most behavioral genetics investigations: (1) A precise definition
      of the phenotype that, as much as possible, unambiguously differentiates the
      study group from the control group must be achieved; (2) environmental and social
      contributions to a trait may exhibit significant sex differences; (3) subsets
      within the study sample may reveal important information about genetic and
      environmental contributions to the trait that otherwise would be missed; (4) the
      high degree of specificity required to define a study sample severely restricts
      the application of results to general populations; and (5) studies attempting to
      replicate data must strictly parallel the original methodology if valid
      comparisons are to be made.

PMID- 9549245
TI  - Developmental psychopathology, personality, and temperament: reflections on
      recent behavioral genetics research.
AB  - Personality, temperament, and psychopathology were until recently largely
      distinct areas of study, each of which emphasized partitioning of heritable and
      environmental variance. The emergence of the paradigm of developmental
      psychopathology along with application of multivariate biometric models to
      behavioral genetic data has defined a second phase of research in these domains.
      Integrated research has begun to map dimensional liability-threshold models of
      psychopathology and to evaluate empirically the categorical versus dimensional
      etiology of traits and disorders. An interesting pattern in the data is that
      psychopathology is probably not merely an extreme of temperament or personality
      in many cases. Variations in temperament and personality are now known to be
      heavily influenced by additive genetic and nonshared environmental factors and to
      exhibit stable or increasing heritability across development. This pattern holds
      for some measures of psychopathology but not for others. For example, shared
      environment effects and decreasing heritability influence much adolescent
      psychopathology, and comorbid problems in young children appear to be due in part
      to shared environment effects. Other recent biometric work on the central problem
      of comorbidity in psychopathology suggests that shared genetic covariation
      accounts for some specific comorbidities but not others. A third phase of
      research is now underway, featuring study of specific molecular gene mechanisms
      by means of linkage and association studies in relation to behavioral phenotypes.
      Complementary integration of discoveries from biometric behavioral studies and
      molecular studies is expected to be the norm for the near future.

PMID- 9549246
TI  - Molecular approaches to child psychopathology.
AB  - Basic research into the genetics of childhood psychiatric disorders has
      substantially increased during the last two decades. Specific genetic mutations
      have been characterized in some developmental disorders (e.g., fragile X syndrome
      and Prader-Willi syndrome), but thus far identification of etiological gene
      mutations in psychiatric illnesses has been unsuccessful. Several psychiatric
      disorders serve as examples of the current state of molecular approaches in child
      psychopathology. Investigations to date of Gilles de la Tourette's syndrome (GTS)
      have not resulted in the discovery of a gene of major effect. Some studies have
      implicated the D2 and D4 dopamine receptors as having a direct role in the
      etiology of GTS, but other studies have disputed those findings. However, the
      dopamine D2 receptor may modulate the severity of GTS. Obsessive-compulsive
      disorder has a reported association with a low-activity allele of the enzyme
      catechol-O-methyltransferase; however, the low-activity genotype is also seen in
      a significant proportion of unaffected individuals. For reading disability two
      distinct phenotypes (phonological awareness and single-word reading) have been
      linked to separate loci on chromosomes 6 and 15. Attention deficit hyperactivity
      disorder (ADHD) has a reported association with the dopamine transporter.
      Findings of a genetic locus for the personality trait of novelty seeking remain
      controversial.

PMID- 9549247
TI  - Nicotine: smoking gun or magic bullet?

PMID- 9549248
TI  - A pilot study of the safety and tolerance of SCH 39166 in patients with
      schizophrenia.

PMID- 9549249
TI  - SSRI discontinuation syndrome related to fluvoxamine.

PMID- 9549252
TI  - Light therapy to treat winter depression in adolescents in Iceland.
AB  - OBJECTIVE: To determine whether light therapy during winter is beneficial to
      adolescents with symptoms of seasonal affective disorder (SAD). SETTING: The 3
      largest colleges in Reykjavik, Iceland. PARTICIPANTS: Eighteen college students,
      18 and 19 years old, suffering from symptoms of SAD. OUTCOME MEASURES: School
      attendance and self-reported change in indicators (concentration, ability to
      awaken in the morning, and frequency of breakfast). RESULTS: Light therapy helped
      some of the students concentrate and wake up in the morning, usually only to a
      mild degree, but did not improve school attendance. CONCLUSIONS: The lack of
      effect of light therapy on school attendance in a group of students with symptoms
      of SAD indicates that school attendance is influenced by several complex factors,
      of which seasonal disorders are not a major determinant, even in those most at
      risk.

PMID- 9549250
TI  - Nicotine: abused substance and therapeutic agent.
AB  - Tobacco dependence is a complex phenomenon that is not fully understood. Nicotine
      is the main alkaloid in tobacco and the addictive compound of tobacco. It can
      improve both mood and cognitive functioning; these positive effects are strong
      reinforcements for smokers and contribute to their addiction. Opposite results
      also have been reported, however, and the effects of nicotine remain
      controversial. Recent epidemiological and empirical studies have indicated that
      smoking or nicotine or both may have protective effects against certain diseases.
      These findings have suggested that nicotine may be used as a therapeutic agent.
      However, because a variety of nicotinic cholinergic receptors are present in the
      brain, new agonist compounds may prove to be more effective than nicotine for
      therapeutic purposes. Studies are reviewed and the suggestion made that nicotine
      may prove useful as a tool to help us understand normal and pathological brain
      functioning.

PMID- 9549253
TI  - What is the optimal approach to the pharmacological management of obsessive
      compulsive disorder?

PMID- 9549251
TI  - Calcitonin and bipolar disorder: a hypothesis revisited.
AB  - Double-blind trials conducted in the early 1980s showed that subcutaneous
      injections of salmon calcitonin in patients suffering from mania resulted in
      significant decreases in irritability, euphoria and hyperactivity. Although these
      results were promising, there were no follow-up studies in this area. A MEDLINE
      search into the effect of calcitonin on neuronal tissues revealed that calcitonin
      affects neuronal tissues in a manner similar to that of the currently accepted
      mood-stabilizing agents--namely by modulating intracellular second messenger
      signalling mechanisms, stabilizing neuronal membranes and inhibiting neuronal
      calcium influx. We suggest that these effects of calcitonin on neuronal tissues,
      combined with earlier clinical research showing its efficacy in treating the
      acute symptoms of mania, make calcitonin a candidate for further research in the
      treatment of bipolar disorder.

PMID- 9549254
TI  - If a patient does not respond to a full dose of fluvoxamine for at least 12
      weeks, what alternatives should be considered?

PMID- 9549256
TI  - Name that drug ... a game with the FDA.

PMID- 9549255
TI  - Better living through research.

PMID- 9549257
TI  - The emperor's new clothes.

PMID- 9549258
TI  - Oral and topical antihistamines: pharmacologic properties and therapeutic
      potential in ocular allergic disease.
AB  - BACKGROUND: Allergic eye disease is a common clinical occurrence in individuals
      who experience local and systemic hypersensitivity reactions. The majority of
      ocular symptoms involve the conjunctiva and lids, which are exposed to the
      environment and thereby are sites of interaction between allergens and
      immunocompetent cells. Signs and symptoms of ocular involvement can manifest as
      itching, chemosis, tearing, swollen lids, and photophobia. METHODS: Histamine is
      a key preformed mediator released when allergen molecules crosslink to antigen
      binding components of adjacent IgE molecules on mast cells or basophil surface.
      On its release, histamine acts on H1-receptors on a variety of tissues and cells,
      including blood vessels, smooth muscle, and sensory nerves. RESULTS: Drugs
      classified as H1-receptor antagonists, commonly referred to as the
      antihistamines, are among the most efficacious and frequently used medications
      for ocular and systemic allergy symptoms. CONCLUSION: This review focuses on the
      pharmacologic actions and side effects of oral first-generation sedating or
      classic H1-receptor antagonists; the second-generation, relatively nonsedating H1
      receptor antagonists; and the topical ocular antihistamine/decongestants and
      single-entity antihistamine formulations.

PMID- 9549259
TI  - Pediatric contact lenses: case reports.
AB  - BACKGROUND: Contact lenses may be a useful, even essential, treatment modality
      for children with a variety of optometric needs. Many clinicians who are
      experienced and capable contact lens practitioners but do not specialize in the
      care of children may refrain from considering contact lenses as a treatment
      option because of a host of perceived problems. Most of these concerns can be
      readily overcome with patience, planning, and education. CASE REPORTS: Five cases
      are presented to illustrate specific clinical problems and the clinical
      application of contact lenses in the pediatric population. CONCLUSION: The case
      reports illustrate the clinical application of contact lens fitting in children
      with a variety of clinical needs. The use of contact lenses in children is an
      ongoing process, requiring great flexibility and creativity on the part of the
      optometrist. Educating the child and the family is an integral part of the
      treatment. The use of contact lenses in children is both an opportunity and a
      challenge that may result in great satisfaction for the child, the family, and
      the optometrist.

PMID- 9549260
TI  - Glaucoma medications, glaucoma therapy, and the evolving paradigm.
AB  - BACKGROUND: Therapy for the glaucomas is dynamic, with changes evolving as new
      medications or modalities are discovered. In comparing the method(s) of treating
      open-angle glaucoma today, as compared to treatment in the 1980s, clear
      differences emerge. While topical beta-blockers remain the mainstay for treatment
      of open-angle glaucoma, other medications and modalities have recently become
      available that supplement their use. Topical carbonic anhydrase inhibitors
      (CAIs), introduced in 1995, have become an important addition to the glaucoma
      armamentarium. They are more useful than their oral counterparts, since they
      cause fewer systemic side effects, with similar efficacy. Brimonidine, a topical
      alpha2-adrenergic agonist, and latanoprost, a topical prostaglandin, have become
      important additions to the glaucoma regimen because of their ability to reduce
      the intraocular pressure (i.o.p.) with an improved therapeutic index, as compared
      to older medications. Finally, argon laser trabeculoplasty (ALT) appears to be a
      safe technique and useful in reduction of IOP. CONCLUSION: The scheme for how the
      anti-glaucoma medications and modalities are used for the therapy of open-angle
      glaucoma will change over time. The evolution will occur as we continue to learn
      more about the drugs presently being used.

PMID- 9549262
TI  - Fluid blood level in cystoid space resulting from central retinal vein occlusion.
AB  - BACKGROUND: A hemorrhagic and cystoid maculopathy developed in a patient with a
      central retinal vein occlusion. There was an unusual finding of a fluid blood
      level in the inferior region of the central large cystoid space. This clinical
      finding has been associated with cystoid macular edema after aphakic/pseudophakic
      cataract surgery. METHOD: A case report is presented and a review of the
      literature was conducted to determine the frequency of this condition and gain
      knowledge of the possibility of the pathophysiology. RESULTS: This is only the
      second case reported in the literature of a fluid blood level seen in a patient
      with obstructive venous retinopathy. The pathophysiology is likely to be the
      transitory bleeding of a retinal vessel into the cystoid space. CONCLUSION: The
      finding of a fluid blood level in a patient with a BRVO or CRVO is a rare event.
      Since this condition has not been associated with diabetic hemorrhagic
      retinopathy, any diabetic patient displaying such a clinical finding should be
      suspected of having obstructive venous disease.

PMID- 9549263
TI  - Preoperative embolization of meningiomas: comparison of superselective and
      subselective techniques.
AB  - We retrospectively compared the efficacy of preoperative superselective and
      subselective embolization for intracranial meningiomas. Between January and
      December 1996, 22 patients (7 men, 15 women, mean age 51 +/- 15.5 yr) underwent
      superselective embolization with 45 to 150 mm polyvinyl alcohol particles after
      superselective catheterization of the feeding vessels with a microcatheter
      system. Another 30 patients (12 men, 18 women, mean age 50 +/- 12.9 yr) underwent
      subselective embolization between January and December 1995 with 150 to 300 mm
      Gelfoam particles after catheterization of the terminal external carotid artery
      just proximal to the orifice of the maxillary artery with a 4- or 5-F
      angiocatheter. The mean intraoperative blood loss (918 versus 1450 mL, p < 0.05),
      amount of blood transfused (4.9 versus 7.5 units, p = 0.09), and surgical
      resection time (422 versus 529 min, p < 0.05) were all lower in the
      superselective group than in the subselective group, while the occurrence of
      fresh ischemic necrosis (59% versus 53%, p = 0.68), hemorrhage (77% versus 60%, p
      = 0.19), and embolic material (55% versus 13%, p < 0.05) on pathologic
      examination were higher in the superselective group. No procedure-related
      complications occurred in the superselective group, whereas two patients in the
      subselective group had postoperative scalp necrosis. Our findings show that
      superselective embolization is more effective than subselective embolization for
      preoperative endovascular devascularization of meningiomas, with significant
      reductions in intraoperative blood loss and surgery time. Preoperative
      embolization of meningiomas, if indicated, should be done with the superselective
      technique whenever feasible.

PMID- 9549261
TI  - Cystoid macular edema associated with the use of latanoprost.
AB  - BACKGROUND: Cystoid macular edema is a common clinical finding following
      intraocular surgery. Certain medications have been associated with an increased
      incidence of cystoid macular edema. This article describes the clinical findings
      in two eyes of two patients in whom cystoid macular edema developed directly
      following treatment with the anti-glaucoma medication latanoprost, and assesses
      the possible causal relationship. CASE REPORTS: Clinical correlative and
      angiographic studies of two patients in a referral practice are presented. The
      main outcome measurement was visual acuity and fundus examination on
      discontinuation of latanoprost. RESULTS: Cystoid macular edema developed in two
      pseudophakic patients after the use of latanoprost. CONCLUSION: Latanoprost
      should be used with caution in pseudophakic and aphakic patients--especially
      those with retinal vascular fragility, any inflammatory uveal disease, or other
      factors that may predispose to the breakdown of the blood-retinal barrier.

PMID- 9549264
TI  - Analysis of corneal topography after excimer laser photorefractive keratectomy.
AB  - Excimer laser photorefractive keratectomy (PRK) is an effective treatment for
      myopia. We investigated the magnitude of optical zone decentration and
      qualitative patterns of corneal topography after this treatment. We performed
      computer-assisted videokeratography on 44 myopic eyes (29 patients) that had
      undergone PRK before and 1, 6, and 12 months after the procedure. Associations of
      clinical outcomes with decentration and topographic patterns were assessed. The
      normalized scale of the topography 1 month postoperatively showed a mean
      decentration of 0.33 +/- 0.23 mm (range 0-0.9). Thirty-four eyes had decentration
      of less than 0.50 mm; 10 had an ablation zone decentered from 0.5 to 0.9 mm.
      Analysis of geometric mean visual acuities between eyes with less than 0.5 mm
      decentration and those with 0.5 to 0.9 mm decentration demonstrated minimal
      differences. No eye was decentered more than 1 mm. Four main ablation patterns
      were noted on subtraction analysis: homogeneous, semicircular, keyhole, and
      central island. Over time, the number of eyes with a homogeneous pattern
      increased. Eyes with a homogeneous ablation pattern had significantly better
      uncorrected visual acuity than those with other patterns. The mean visual acuity
      was 20/29.1 in the homogeneous group and 20/38.5 in the pooled irregular group 1
      month postoperatively (p < 0.05). There was no significant difference among the
      four ablation patterns at 6 or 12 months after PRK. Topographic patterns were not
      significantly associated with best-corrected vision.

PMID- 9549265
TI  - Absorbable PDS-II suture and nonabsorbable polypropylene suture in aortic
      anastomoses in growing piglets.
AB  - The long-term outcome of vascular anastomoses in children can be compromised by
      stenosis when the growth of the anastomosis does not match that of the vessels.
      This can be influenced by the suture material. We evaluated the suitability of
      the new generation of polydioxanone (PDS-II), an absorbable synthetic
      monofilament suture, in vascular surgery, in terms of permitting normal growth of
      aortic anastomoses. Ten piglets underwent primary end-to-end anastomosis of the
      thoracic aorta, five with PDS-II suture and five with conventional polypropylene
      (Prolene) suture. Six months after surgery, an aortogram was obtained for each
      animal. The piglets were then killed and the aortas were sent for pathologic
      examination. Complete absorption of suture material with slight dilatation of the
      anastomoses was found in all five pigs in the PDS-II suture group. We also found
      thrombus formation in one pig in this group. Mild stenosis of the anastomotic
      site was noted in all five pigs in the polypropylene suture group, but no
      intraluminal thrombus formation was seen. The degree of dilatation or stenosis
      within each group was not significantly different when intraluminal diameters
      were compared at three distinct sites in the reconstructed aorta (p > 0.05). The
      differences in vascular growth between the two groups were also not significant
      (p > 0.05). Histologic examination revealed less tissue reaction in the PDS-II
      suture group than in the polypropylene suture group. Thus, PDS-II seems to be a
      suitable suture material for anastomoses as far as vascular growth is concerned,
      but the possibility of aneurysm formation secondary to dilatation of the
      anastomotic site should be kept in mind.

PMID- 9549266
TI  - Factors affecting postoperative fecal soiling in Hirschsprung's disease.
AB  - We retrospectively assessed the factors that may contribute to fecal soiling
      after surgery for Hirschsprung's disease. Fifty-eight patients underwent surgery
      for Hirschsprung's disease and returned for follow up. The patients were divided
      into two groups based on the presence or absence of fecal soiling. The
      postoperative period, level of bowel pulled through, stool frequency, stool
      character, presence or absence of anorectal surgical complications, and
      manometric findings of the two groups were compared. Forty-three patients (40
      boys, 3 girls, mean age 9.5 yr) had soiling and 15 (10 boys, 5 girls, mean age
      10.2 yr) did not. Patients with soiling had significantly higher rates of
      anorectal surgical complications (60% vs 7%), abnormal stool character (75% vs
      7%), stool frequency greater than three times per day (63% vs 20%), absence of
      rectoanal inhibitory reflex (33% vs 2%), and narrow anorectal pressure gradient
      (60% vs 13%) than those without. The results of manometric study suggested that a
      damaged internal sphincter or irritable neorectum might have contributed to fecal
      soiling. In conclusion, although anorectal surgical complications might result in
      both irritable neorectum and damaged internal sphincter, their effect on the
      neorectum (significantly increased rate of high resting rectal pressure) seemed
      to outweigh that on the internal sphincter. A competent anal sphincter and a less
      irritable neorectum after operation may therefore lower the likelihood of fecal
      soiling.

PMID- 9549267
TI  - Association of active myofascial trigger points and cervical disc lesions.
AB  - We investigated the occurrence of active myofascial trigger points in specific
      muscle groups in relation to the existence of cervical disc bulging at various
      levels. One hundred and five patients (48 men, 57 women; mean age, 45.8 +/- 12.1
      yr) who had active trigger points in the neck or upper back after trauma were
      divided into two groups on the basis of magnetic resonance imaging (MRI) evidence
      of bulging disc(s). The discN group consisted of 46 patients who had normal MRI
      findings in the cervical spine. The other 59 patients, with mild cervical disc
      bulging, were assigned to the disc' group. The correlations between specific
      muscles with active trigger points (clinical finding) and cervical disc lesions
      at specific levels (MRI finding) were analyzed. There were significant
      associations between the level of disc lesion and the muscles with trigger
      points, namely C3-4 lesions with levator scapulae and latissimus dorsi trigger
      points; C4-5 lesions with splenius capitis, levator scapulae, and rhomboid minor
      trigger points; C5-6 lesions with splenius capitis, deltoid, levator scapulae,
      rhomboid minor, and latissimus dorsi trigger points; and C6-7 lesions with
      latissimus dorsi and rhomboid minor trigger points. For each disc level, the
      average pain intensity (assessed using a numerical analog scale) of trigger
      points in certain correlated muscles (as indicated above) in the disc group was
      significantly higher than that in the discN group (p < 0.05 for all disc levels).
      We conclude that active trigger points are more likely to occur in certain
      muscles in the presence of cervical disc lesions at specific levels.

PMID- 9549268
TI  - Extravesical detrusorrhaphy for vesicoureteral reflux in children.
AB  - Extravesical detrusorrhaphy is a simple and safe approach to antireflux surgery;
      however, its use in Taiwan has seldom been reported. We report the outcomes of 15
      patients (23 ureters) with primary vesicoureteral reflux who underwent
      extravesical detrusorrhaphy between January 1995 and April 1996, and describe the
      surgical technique. Overall, vesicoureteral reflux was cured in 22 of 23 ureters.
      Postoperative morbidity and complications were minimal. None of the patients had
      obstruction or significant hematuria. The discomfort related to bladder spasms
      during the postoperative period was subjectively decreased compared to the
      conventional transvesical technique. There was transient voiding inefficiency in
      three patients, as well as urinary retention in one, which resolved spontaneously
      after 4 weeks of Foley catheter drainage. Our experience showed that
      detrusorrhaphy is an effective way to correct vesicoureteral reflux with minimal
      morbidity and discomfort. Proper patient selection and strict adherence to the
      surgical principle are important for high success rates.

PMID- 9549269
TI  - Mucopolysaccharidosis type II (Hunter's syndrome) in Taiwan.
AB  - The mucopolysaccharidoses are a group of inherited disorders of lysosomal storage
      of glycosaminoglycans. Among them, mucopolysaccharidosis (MPS) type II (Hunter's
      syndrome), caused by a deficiency in iduronate sulfatase, is the only one
      inherited in an X-linked recessive manner. We describe 12 Hunter's syndrome
      patients and seven carriers, with precise analysis of glycosaminoglycan content
      in urine and iduronate sulfatase activity in cultured fibroblasts and plasma.
      Their ages at the time of diagnosis ranged from 1 year 10 months to 11 years
      (mean 4.3 yr). The delay in diagnosis was from 1 month to 5 years (mean 2.1 yr)
      after the initial presentation. The most frequent initial complaints of the
      patients were delayed developmental milestones (75%) and speech (67%), although
      all patients were found to have coarsening of facial features at diagnosis. The
      difficulties in disease recognition allowed disease recurrence in four of the 11
      families. Prompt clinical suspicion and referral will be important in genetic
      counseling for MPS type II and its management, if definitive therapy becomes
      available.

PMID- 9549270
TI  - Stress-reducing effect of physician's tape-recorded support on cardiac surgical
      patients in the intensive care unit.
AB  - Staying in an intensive care unit (ICU) is very stressful for patients after
      heart surgery. Although it is a general belief that support from doctors is
      important to reduce patients' tension, no quantitative data are available. We
      investigated the stress-reducing effects of a tape-recorded message from the
      physician which provided information regarding the surgery and emotional support
      for heart surgery patients postoperatively in the ICU. Sixty patients who
      underwent cardiac surgery were randomly allocated to two equal groups. The
      patients in the experimental group listened to a tape-recorded message from their
      attending surgeon soon after they recovered from anesthesia, while the control
      group rested during the study period. The effectiveness of the tape-recorded
      support program was evaluated by the influence on heart rate, blood pressure, and
      finger skin temperature, as well as the degree of subjective pain, tension,
      anxiety, depression, and anger. The pain and tension levels of the patients were
      measured using a visual analogue scale, while the severity of anxiety,
      depression, and anger was evaluated using the Brief Symptom Rating Scale.
      Patients' evaluation of the usefulness of the program was also assessed. After
      listening to the physician's recorded message, the mean increase in the skin
      finger temperature in the experimental group was higher than in the control group
      (0.44 degree C vs 0.25 degree C, p = 0.0513). The experimental group had
      significant decreases in their mean scores of pain (-1.11 vs 0.36, p = 0.0043),
      tension (-2.26 vs -0.25, p = 0.0001), anxiety (-1.3 vs -0.57, p = 0.0473), and
      depression (-2.24 vs -0.37, p = 0.0253). The patients showed a high need for this
      support program (mean need score 8.4). These findings show that a physician's
      tape-recorded message providing information and emotional support can reduce
      stress in heart surgery patients in the ICU postoperatively.

PMID- 9549271
TI  - Ultrasound-guided fine needle aspiration biopsy in the diagnosis of pulmonary
      cryptococcosis.
AB  - The purpose of this study was to assess the safety and reliability of ultrasound
      guided fine needle aspiration biopsy (US-guided FNAB) combined with modified
      Papanicolaou's staining in the diagnosis of pulmonary cryptococcosis. The study
      included 10 patients (9 men, 1 woman, 28-70 yr). Percutaneous US-guided FNAB was
      performed through a puncture probe with central channel guidance (n = 8) or in a
      'free-hand' manner (2), depending on the size of the lesion and the experience of
      the operator. Sonography disclosed homogeneously hypoechoic lesions with air
      bronchograms over the peripheral or central portion in nine patients, and
      occasional heterogeneous echogenicity with necrotic tissue without air
      bronchogram in one. Thirteen lesions were found on the chest radiographs of the
      10 patients; these could be divided into three patterns: infiltrates (2), nodules
      or masses (7), and consolidation (4). Using US-guided FNAB and immediate modified
      Papanicolaou's stain, a diagnosis of pulmonary cryptococcosis was confirmed in
      nine of the 10 patients. The remaining case was proven by surgical resection. No
      major complications developed after US-guided FNAB. We conclude that this
      technique, combined with modified Papanicolaou's staining, provides a safe,
      rapid, and reliable method for diagnosing pulmonary cryptococcosis.

PMID- 9549272
TI  - Evaluation of an automatic polymerase chain reaction assay for identification of
      Mycobacterium tuberculosis in respiratory specimens.
AB  - We evaluated the performance of an automatic polymerase chain reaction (PCR)
      detection system for identification of Mycobacterium tuberculosis in respiratory
      specimens. Six hundred and two respiratory specimens, including 557 sputa and 45
      bronchial washing samples, were analyzed using the COBAS AMPLICOR Mycobacterium
      tuberculosis (MTB) test. The results were compared with those obtained from acid
      fast microscopy, conventional culture, and clinical history. In cases of
      discrepancy between the results of the COBAS AMPLICOR MTB test and culture, the
      medical history of the patient was reviewed, the COBAS AMPLICOR MTB test was
      repeated, and the gene encoding M. tuberculosis superoxide dismutase was screened
      using PCR (SOD-PCR). Fourteen samples were excluded because the internal control
      test result was negative. Of 57 specimens that were culture positive for
      Mycobacterium species, 40 appeared to have growth of M. tuberculosis and 21 were
      smear positive for acid-fast bacteria. The sensitivity, specificity, and positive
      and negative predictive values for the COBAS AMPLICOR MTB test evaluated at our
      laboratory were 85.0% (34/40), 99.3% (544/548), 89.5% (34/38), and 98.9%
      (544/550), respectively. Three specimens that were culture positive for M.
      tuberculosis but negative by COBAS AMPLICOR MTB test were positive when rechecked
      by both COBAS AMPLICOR MTB test and SOD-PCR. Among the four specimens with
      positive reactions on both COBAS AMPLICOR MTB test and SOD-PCR that were culture
      negative, two were from patients who had been receiving antituberculosis
      treatment, one was from a patient who had been treated for tuberculosis for 1
      year, and the other was from a patient who died of sepsis with adult respiratory
      distress syndrome. In more than 70% of smear-negative and culture-positive
      specimens and 86.4% of smear-positive specimens, M. tuberculosis was identified
      by the COBAS AMPLICOR MTB test within 10 hours after receipt of the specimens.
      Our data show that the COBAS AMPLICOR MTB test provides rapid and accurate
      detection of M. tuberculosis in respiratory specimens.

PMID- 9549273
TI  - Medullary cystic disease: a family study.
AB  - Medullary cystic disease of the kidney is characterized by progressive
      tubulointerstitial disease with medullary cyst formation and secondary glomerular
      sclerosis. We treated a patient with chronic renal failure and investigated the
      family history of renal disease. The patient, an 18-year-old woman, was admitted
      due to poor appetite and fatigue for several months. Findings on physical
      examination were normal except for a pale conjunctiva. Urinalysis revealed only
      mild proteinuria with clear sediment. The hemogram showed normocytic normochromic
      anemia with hemoglobin 86 g/L. The patient was azotemic and her creatinine
      clearance rate was 10.7 mL/min. Renal sonography showed contraction of both
      kidneys with a marked increase in cortical echogenicity. One small cyst was found
      in the medullary area. Computed tomography (CT) and magnetic resonance imaging
      revealed several medullary cysts. Percutaneous renal biopsy showed focal and
      periglomerular sclerosis, marked tubular atrophy, and interstitial fibrosis. Ten
      of her family members were examined for renal function, and by sonography and CT.
      Five had medullary cysts, and three of the five showed abnormal renal function.
      Medullary cystic disease should be considered in the differential diagnosis of
      patients with renal disease and a positive family history.

PMID- 9549274
TI  - Amebic liver abscess complicated with cardiac tamponade and mediastinal abscess.
AB  - Amebic pericarditis is an extremely rare complication of liver abscess and an
      uncommon etiology of sterile pericardial effusion with cardiac tamponade. The
      association of mediastinal abscess in this clinical setting has not been reported
      in the literature. Herein, we describe a case of amebic liver abscess complicated
      with mediastinal abscess and amebic pericarditis with cardiac tamponade. A 44
      year-old man was admitted to our hospital because of shortness of breath for the
      previous 2 days. Cardiac tamponade was diagnosed and emergency pericardiectomy
      was performed. Chocolate-like pus was found in the pericardial sac and
      mediastinal space during surgery. Abdominal computed tomography revealed an ill
      defined hypodense lesion over the left lobe of the liver, suggesting a liver
      abscess. Amebic liver abscess and pericarditis were diagnosed on the basis of a
      high serum titer of amebic antibodies on hemagglutination test. The patient was
      treated with metronidazole for 2 weeks and discharged in good condition. This
      case should alert clinicians to the possibility of amebic pericarditis in
      patients with cardiac tamponade associated with chocolate-like sterile pus in the
      pericardium and mediastinum. To establish the diagnosis of amebic pericarditis,
      one should investigate the presence of a liver abscess, a high serum titer of
      amebic hemagglutination antibodies, and the presence of Entamoeba histolytica
      trophozoites in the pericardium or pericardial aspirate.

PMID- 9549276
TI  - Diagnosis of pulmonary sequestration by magnetic resonance imaging.
AB  - Pulmonary sequestration, an uncommon congenital anomaly, is traditionally best
      diagnosed using arteriography; however, this is invasive and not without risk of
      morbidity and mortality. We report two patients with pulmonary sequestration
      diagnosed using magnetic imaging techniques. The first was a 22-year-old woman
      and the second a 17-year-old boy, both of whom presented with symptoms of cough
      and exertional dyspnea. Pulmonary sequestration was suspected from their chest
      radiographs. Magnetic resonance imaging and magnetic resonance angiography
      clearly demonstrated the aberrant artery arising from the aorta in a single
      noninvasive examination that did not require the use of contrast medium. We
      recommend magnetic resonance imaging as a safe, efficient, and noninvasive
      modality for the diagnosis of pulmonary sequestration.

PMID- 9549275
TI  - Successful resection of a teratoma of the third ventricle in a 3-year-old boy.
AB  - Few cases of teratoma in the third ventricle have been reported in detail. We
      describe a 3-year-old Chinese boy presenting with increased intracranial
      pressure, headache, and vomiting. Preoperative computed tomography and magnetic
      resonance imaging demonstrated a teratoma in the third ventricle. Complete
      excision of the tumor was achieved through the interhemispheric transcallosal
      approach. The patient did well and was without neurologic deficits
      postoperatively. Although the majority of tumors located in the third ventricle
      are malignant and can penetrate the brain tissues that constitute the wall of the
      third ventricle, mature teratomas are an exception and total removal may be
      possible.

PMID- 9549277
TI  - [Emergencies (outpatients) in cardiosurgery: national multicenter study. Gruppo
      di Studio SIAARTI "Anestesia e Rianimazione in Cardiochirurgia"].
AB  - BACKGROUND: Heart Surgery Italian Centres participated in this study to define
      the rate and the outcome of outpatients' cardiovascular emergencies. Hospital
      patients and heart and/or lung transplants were excluded. METHODS: Data were
      prospectively collected over 6 months (from April 1 through September 30, 1996)
      and analyzed using SPSS stat programme. RESULTS: 731 emergencies (5.8% of 12551
      cardiosurgical procedures) have been recorded. 85.8% of the patients were
      admitted to the surgical units, coming from other hospitals. 31.6% of emergencies
      were admitted in the night. 37.2% of the patients were admitted because of
      myocardial infarction or unstable angina in spite of e.v. drugs; 28.3% because of
      dissection of thoracic aorta; 18.2% were congenital heart diseases; 9.2% valvular
      or valve prosthesis dysfunctions; 7.1% were affected by other cardiovascular
      diseases. On admission, 48.7% of the patients were in cardiogenic shock or severe
      heart failure, 27.9% presented respiratory failure, 11.8% renal failure, 5.1%
      brain injury (coma and/or plegia or paresis). 500 (68.4%) patients needed
      invasive and or not invasive diagnostic procedures. 33 (4.5%) patients died early
      after admission to the hospital. 30 patients, who did not need surgery, were
      discharged few days after admission. 668 (91.4%) patients underwent surgery.
      Overall perioperative mortality was 21.7%: 31.6% in the aortic group, 21.6% in
      the congenital heart disease group, 24.6% in the valve group, 15.2% in the
      coronary group. CONCLUSIONS: The cost of outpatients' cardiovascular emergencies
      is very high. First of all, overall mortality and perioperative mortality are
      greater when compared to elective surgical procedures; moreover expensive tools
      and continuous availability of skilled anaesthesiologists, cardiologists and
      surgeons are mandatory. In order to optimize results (cost/benefit) and looking
      for lowering mortality, the approach to outpatients' cardiovascular emergencies
      in Italy must be reorganized, in order to refer emergencies to few, high
      qualified, "ad hoc" organized Centres properly placed on the national territory.

PMID- 9549278
TI  - [Neurologic prognosis after cardiocirculatory arrest outside the hospital].
AB  - OBJECTIVE: To detect clinical signs and times of evaluation able to identify
      patients with good neurologic prognosis after out-of-hospital cardiac arrest.
      EXPERIMENTAL DESIGN: Retrospective study with 6 months-2 years of follow-up.
      SETTING: General intensive care unit, from 1993 to 1995. PATIENTS: Twenty-three
      patients aged 18-80 years, admitted with coma after out-of-hospital cardiac
      arrest, who survived at least 24 hours, without concomitant neurologic disorders.
      INTERVENTIONS: Neurologic outcome classification in three categories: complete
      neurologic recovery (A), moderate to severe disability (B), death without
      regained consciousness (C); A and B groups of patients are considered together as
      a "good neurologic outcome" group. MEASUREMENTS: Evaluation of some neurological
      parameters (GCS, motor response to pain, spontaneous motility, cranial nerve
      reflexes, spontaneous breathing, seizures) 6 hours (t0), 24 hours (t1), 72 hours
      (t2) and 7 days (t3) after arrest. RESULTS: Patients with good prognosis are
      identified with 100% sensitivity from the following parameters: at t0 none; at t1
      motor response to pain, GCS > 4, absence of seizures; at t2 the former
      parameters, spontaneous breathing, brain stem reflexes, normal pupils; at t3 all
      the former parameters and spontaneous motility. Specificity is greater than 50%
      only for motor response to pain and GCS > 4. CONCLUSIONS: It is mostly impossible
      to state a neurologic prognosis in the first hours after cardiac arrest. The
      single predictor with the most reliable prognostic value is motor response to
      pain which allows, if present, to identify all the patients with a good prognosis
      as early as 24 hours after arrest.

PMID- 9549279
TI  - [Measurement of cardiac output with continuous thermodilution. b1 Clinical
      experience with the Intellicath-Vigilans system].
AB  - BACKGROUND: Thermodilution cardiac output measurements are commonly obtained by a
      manual bolus technique with a pulmonary artery catheter. METHODS: A new
      thermodilution catheter has been developed which utilizes an integral thermal
      filament and provides semicontinuous online cardiac output. The response of this
      new device in 25 patients undergoing coronary artery bypass grafting was
      examined. A total of 250 data pairs was obtained; the cardiac outputs ranged from
      2.2 to 11.9 lts.min. RESULTS: The linear regression is represented by the
      following equation: continuous thermodilution = 0.7196 bolus thermodilution
      +1.038. The correlation coefficient was 0.75; the mean bias was 0.493 +/- 1.034.
      CONCLUSIONS: The new technique provides acceptable accuracy in many clinical
      situations except when sudden haemodynamic changes occur.

PMID- 9549280
TI  - [An index of daily intensive care unit activity].
AB  - OBJECTIVE: To set up an index for the evaluation of type of interventions and
      procedures applied a prerequisite for the evaluation of appropriateness of ICU's
      activity. DESIGN: Observation prospective study. PATIENTS: 2507 patients out of
      the 5030 enrolled in the cohort study. MEASUREMENTS: A cross-sectional assessment
      of the volume and intensity of treatment--level of care--delivered to patients
      was performed at a preidentified index day. A check list of procedures was
      utilized. Intensive high level treatment was demonstrated by the application of
      procedures suggesting one or more organs or vital functions intensively
      supported. Sub-intensive treatment was defined by the application of procedures
      indicating monitoring or treatments not exclusively performed in intensive
      environment. RESULTS: 3955 samples were collected over 9 index days; 2707 (68.3%)
      resulted in intensive, 1227 (30.7%) subintensive or intermediate and 41 (1%) ward
      treatments. Out of the intensive samples, 63.4% received only one intensive
      procedure, while 27.9% two. Ventilatory support was the most frequently (90.4%)
      utilized intensive procedure. Overall 99% of the samples were characterized by
      treatments/procedures too invasive for normal ward. CONCLUSIONS: The proposed
      method gives the opportunity to easily evaluate the level of care and then the
      appropriateness of ICU care.

PMID- 9549282
TI  - [Late awakening].

PMID- 9549281
TI  - Treatment of severe acidemia in a young woman affected by diabetic ketoacidosis.
AB  - The case of a 32-year-old woman admitted to Hospital for diabetic coma (GCS 8),
      with arterial blood pH below usually reported vital range, is described. After
      First Aid admittance an arterial blood gas analysis adjusted for patient's
      temperature showed PaO2 10.77 kPa, PaCO2 7.8 kPa, pH 6.52, HCO3 5 mmol/L, BE
      34.9. A significant increase of lactate and butyrate concentration was also
      found. The patient was intubated and breathing was assisted for a 60 hour period
      after ICU admission, while acidemia was treated by THAM and bicarbonate
      associated to potassium i.v. infusion (infusions were titrated on acid-base and
      electrolyte concentration direct monitoring). After progressive neurological and
      biochemical improvement, 7 days after ICU admission the patient was moved to an
      Internal Medicine department. This case demonstrated that during diabetic
      ketoacidosis, despite very low pH (below reported vital range), an invasive
      intensive treatment could give complete cure without neurological sequelae.

PMID- 9549283
TI  - Comparison of cilostazol with warfarin as antithrombotic therapy after femoro
      popliteal bypass surgery using an ePTFE graft.
AB  - BACKGROUND: Cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4- dihydro
      2(1H)-quinolinone) is a new antiplatelet agent with a vasodilating action. The
      purpose of this study was comparison of cilostazol with warfarin as
      antithrombotic therapy after femoro-popliteal bypass surgery using an expanded
      polytetrafluorethylene (ePTFE) graft. EXPERIMENTAL DESIGN: This report is a
      retrospective study and the patients were followed up for five years. SETTING:
      Outpatients of university hospital. METHODS: Sixteen arteriosclerosis obliterans
      patients, who were diagnosed as having only superficial femoral artery stenosis
      or occlusion, underwent femoro-popliteal (above the knee) bypass using an ePTFE
      graft 6 mm in diameter. Cilostazol (150-200 mg/day) was administered to 6 cases
      (9 bypasses), and warfarin (prothrombin time was controlled to 15-25%.) was
      administered to 10 cases (14 bypasses). RESULTS: No clinically characteristic
      differences were found between the two groups. The cumulative 1-, 3-, and 5-year
      primary and secondary graft patency rates were 69% and 80%, 69% and 80%, and, 69%
      and 80% in the cilostazol group, vs 61% and 91%, 51% and 91%, and, 51% and 91% in
      the warfarin group, respectively. These differences were not significant (p <
      0.05). No hemorrhage complications were observed in the cilostazol group. The
      management of cilostazol administration was safe and simple. CONCLUSIONS:
      Although the number of cases was small in this study, cilostazol was considered
      to be as effective as warfarin and suitable for the postoperative antithrombotic
      therapy after the ePTFE bypass surgery.

PMID- 9549284
TI  - [So-called "spontaneous" lesions of the popliteal artery].
AB  - The term "spontaneous", when attributed to a stenotic or obliterative arterial
      lesion, could seem ambiguous and doesn't completely explain the anatomical
      substrate that is the basis of this morbid condition. However, it is true that
      injuries can occur without the patient being aware of any traumatic event, and
      can cause a symptomatology arising suddenly and, apparently, "spontaneously". In
      this study, three cases of patients observed for acute or chronic lower limb
      ischemia are presented. All patients were male, young and underwent an
      angiographic examination that demonstrated, in an otherwise normal arterial tree,
      filling defects or obstruction involving the popliteal artery. Two patients
      underwent a reconstructive surgical procedure. The third was medically treated.
      CAT or MNR examinations were performed in order to exclude developmental defect
      such as an anomalous course of popliteal artery determined by a displacement due
      to medial head of the gastrocnemius muscle. Actually in these three cases, a
      definite etiology of the arterial damage was not demonstrated and therefore it is
      suggested that a physical effort could have injured an already weakened arterial
      structure.

PMID- 9549285
TI  - [A case of deep vein thrombosis].
AB  - The case of a woman admitted to hospital various times because of the onset of a
      mantle-like oedematous syndrome is reported. Observations revealed a narrowing at
      the level of the internal jugular and right subclavian veins with total
      obliteration of the right anonymous vein caused by previous thrombosis induced by
      intravenous implantation of a pace-maker.

PMID- 9549286
TI  - [Thromboendarterectomy of the superficial femoral artery with a femoro-popliteal
      endoprosthesis. Technical note on a preliminary experience].
AB  - BACKGROUND: The authors report an early experience with a new endovascular
      approach in the treatment of occlusive superficial femoral artery disease to
      evaluate the efficacy and the feasibility of the new technique. METHODS AND
      RESULTS: Four patients with disabling claudication or leg rest pain were treated
      for long segment occlusion of superficial femoral artery (SFA). A remote
      endarterectomy (EA) of SFAs has been performed using a single groin incision and
      a conventional Vollmar ring stripper to remove the entire atheroma core for a
      length of 20, 10, 9 and 8 cm. In 3 cases following complete extraction of intimal
      core and a guidewire placement across from the distal endpoint, the
      endarterectomized segment was lined endoluminally by implanting one or more Self
      Expanding Coated Stent (Meadox Passager 6-10 mm); the stent was positioned under
      fluoroscopic guidance to prevent dissection without any further balloon-dilation.
      In 1 case a 5 mm diameter thin-walled PTFE endoluminal graft was positioned using
      a Strecker stent for distal fixation. One patient had an immediate post-operative
      occlusion of distal stent which required a femoro-popliteal autologous vein
      bypass. In the remaining 3 cases no postoperative complications were observed and
      the patients are asymptomatic with normal flow through the stent and the
      endoluminal PTFE graft at 6 months. CONCLUSIONS: In this report a combined
      surgical and endovascular procedure has been proposed. A prospective randomized
      study is carrying on at our Institute to verify if EA+ endovascular grafting of
      SFA represents an alternative to traditional femoro-popliteal vein bypass.

PMID- 9549287
TI  - [Current role of thrombendarterectomy in chronic peripheral obstructive
      arteriopathy].
AB  - BACKGROUND: The authors report the present indications for thromboendarterectomy
      (TEA) and the advantages it offers for the surgical treatment of steno
      obstructive lesions of aortoiliac and femoro-popliteal regions. They illustrate
      this method and the necessary instruments and describe the technique in detail,
      for the good outcome of revascularization. METHODS: Then personal surgical
      experience in 46 patients during the period from January 1985 to December 1995,
      is reported. Epidemiological data (sex, average age, risk-factors, concomitant
      diseases), different types of surgical operations (TEA "open air", TEA
      "semiclosed", TEA in association with bypass), clinical and instrumental
      preoperating study, invasive or not, medical therapy during and after operation,
      immediate and remote check-up are then reported. RESULTS AND CONCLUSIONS: The
      results in terms of cumulative pervious vessel and salvage of the arm, compared
      with different stages of the disease and a 5 years- follow-up are reported. The
      effectiveness of TEA is confirmed in the symptomatic improvement and salvage of
      the arm, and the lower costs, when the indications and the accuracy of surgical
      technique are respected.

PMID- 9549288
TI  - Nitrite plasma levels in acute and chronic coronary heart disease.
AB  - BACKGROUND: The authors carried out a study on the plasmatic levels of nitrites,
      which are the sole stable metabolites of nitric oxide (NO), in a group of
      subjects suffering from various clinical forms of coronary artery disease, aimed
      at evaluating the endothelial production of NO in acute and chronic ischemic
      conditions. METHODS: Our series consisted of 104 female subjects (mean age 65 +/-
      5) subdivided into: a) 10 subjects with acute coronary heart disease (myocardial
      infarction); b) 32 with chronic non hypertensive coronary heart disease (CHD); c)
      30 with hypertensive CHD (arterial blood pressure over 160/95 mmHg); d) 32 with
      CHD and hypercholesterolemia (values over 250 mg/dl). Thirty-seven female
      subjects (mean age 58 +/- 7) without internistic diseases were considered as
      control subjects. For each sample the plasmatic levels of nitrites were
      determined by the Gutman and Hollywood method. RESULTS: We discovered that in the
      patients with chronic coronary heart disease (CHD) the mean value of nitrites was
      18 +/- 0.3 mumol/L, not significantly different from the controls (17 +/- 0.5
      mumol/L). In the patients with acute CHD the nitrite plasma level were
      significantly (p < 0.05) higher (30 +/- 2.2 mumol/L) compared to the controls and
      the patients with chronic CHD. In the group of patients with hypertensive CHD the
      mean nitrite value was 20 +/- 0.6 mumol/L, significantly (p < 0.05) higher in
      comparison with the group of non-hypertensive CHD patients (14 +/- 0.3 mumol/L).
      In the subjects with CHD and hypercholesterolemia the mean value of nitrites was
      sharply elevated, (25 +/- 1.0 mumol/L), with a highly significant difference (p <
      0.01) as compared to the normolipemic CHD patients. CONCLUSIONS: These results
      lead to the hypothesis that: strong NO production may play a compensatory and
      protective role during acute myocardial hypoxia; NO defective synthesis may
      depend on an exhaustive endothelial adjustment in subjects with long-term CHD; a
      significant increase of the relaxing factor in hypertensive conditions exists; a
      highly enhanced synthesis of the plasmatic nitrites in hypercholesterolemic
      patients means an engagement of NO to neutralize the endothelium-damaging
      molecular substances and particularly the oxided LDL.

PMID- 9549289
TI  - [Correlations between the efficacy of thrombolytic therapy and appearance of
      abnormal Q waves in the early stages of acute myocardial infarction].
AB  - BACKGROUND: The purpose of this study was to determine the time course of the
      appearance of abnormal Q waves on the electrocardiogram (ECG) over the first 6
      hrs of the symptoms of acute myocardial infarction (AMI) and to determine what
      implications, if any, such Q waves have for the efficacy of thrombolytic therapy.
      Severe myocardial ischemia can produce early QRS changes in the absence of
      infarction. Abnormal Q waves on the baseline ECG may not be an accurate marker or
      irreversibly injured myocardium. METHODS: A study of 232 patients with AMI
      consecutively admitted to our coronary care units was carried out. Patients with
      previous AMI were not included. The presence and number of abnormal Q waves, as
      defined by Selvester, on the initial ECG was determined for each patient. The
      presence or absence and magnitude of ST segment elevation and depression were
      recorded and these data were used to estimate the left ventricular infarct size
      should thrombolytic therapy not be given (Aldrich score). Quantitative thallium
      201 tomographic imaging was performed after a mean of 42 +/- 40 days from
      hospital discharge in 145 patients. RESULTS: In patients admitted within 1 hr of
      symptoms, 53% had abnormal Q waves on the initial ECG independent of the duration
      of symptoms before therapy (p < 0.001). Despite this finding, the presence of
      abnormal Q waves on the admission ECG did not eliminate the effect of
      thrombolytic therapy on reducing final infarct size (p < 0.001). CONCLUSIONS:
      Abnormal Q waves are a common finding early in the course of AMI. However, there
      is no evidence that abnormal Q waves are associated with less benefit in terms of
      reduction of infarct size after thrombolytic therapy.

PMID- 9549290
TI  - [Treatment of post-transplant erythrocytosis: comparison of lisinopril and
      theophylline].
AB  - OBJECTIVE: The proposal of this study is to compare the efficacy of lisinopril
      and theophylline, alone or in association, on erythrocytosis in renal
      transplanted patients. DESIGN: Prospectic, case-control study.
      PATIENTS/ENVIRONMENT: 15 inpatients meeting 3 main criteria: 1) ACE therapy for
      past erythrocytosis, 2) actual erythrocytosis, 3) symptomatic increase of
      haematocrit (Hct). INTERVENTION: The treatment has been divided into 3
      consecutive phases of 30 days each: 1) lisinopril (5 mg/die), 2) theophylline (4
      mg/kg/die), 3) association of 2 drugs. MEASUREMENTS: The evaluations were
      scheduled at the beginning and every month and consisted of renal function
      control, haemochromocytometric exam, serum level of folates, B12 vitamin and
      erythropoietin (EPO), iron level, cyclosporinemia, as well as clinic control and
      adverse events detection. RESULTS: A significative decrease of Hct values and a
      decrease of serum erythropoietin values was observed in patients treated with
      lisinopril. Patients treated with theophylline showed a significant reduction of
      Hct values causing a reduction of erythropoietin serum level in 8/13 patients.
      Lisinopril and theophylline administered in combination presented a significant
      decrease of Hct values, while EPO values diminished compared to basal values.
      CONCLUSIONS: These data showed that lisinopril is a valid therapy for the
      treatment of posttransplanted patients affected by erythrocytosis and, moreover,
      has the benefit of antihypertensive action. Theophylline remains an alternative
      therapy when ACEi are contraindicated. The combination of the 2 drugs doesn't
      produce additional benefits.

PMID- 9549291
TI  - [Longitudinal echocardiographic study of HIV positive patients].
AB  - BACKGROUND: From May 1992 to June 1996 the authors have studied a group of 39
      subjects with positive anti-HIV, with echo 2D color Doppler examination, to
      evaluate with semi-annual controls, the wide variety of cardiac complications in
      the various phases of clinical evolution of the illness. METHODS: At the moment
      of recruiting, all the subjects with HIV infection were asymptomatic A1 (HIV +
      As). The patients whose average age was 29 +/- 5, were composed of 60% drug
      addicts, 17% homosexuals, 8% haemophiliacs and for the 15% heterosexual. RESULTS:
      The most frequent cardiac complications are represented by hypokinesia of the
      left ventricle (h-aLV) and by pericardial effusion (PE); more rarely of
      endocardial vegetations (EV), dilatation of the left ventricle (dLV) and
      tricuspid insufficiency (TI). The entity of damage and the number of cases
      observed, are correlated with the grade of clinical severity of the illness.
      CONCLUSIONS: In accordance with the literature data, cardiac pathologies,
      particularly in the first phases of the illness, are asymptomatic or
      paucisymptomatic, making the clinical-instrumental observation of the patient
      useful also in cardiology.

PMID- 9549292
TI  - [Precordial discomfort and ECG changes of repolarization associated with
      hypomagnesemia in a young women following colectomy for diffuse colonic
      lipomatosis].
AB  - Aim of this paper is to describe and discuss, on the basis of the available
      literature, the case of a young woman, previously colectomized for diffuse
      lipomatosis of the colon, showing hypomagnesemia and symptomatic (precordial
      discomfort) changes of repolarization phase, detected by ECG, probably due to
      coronary spasm. This hypomagnesemia (1.4 mEq/1) was probably due to altered
      intestinal absorption of magnesium, linked to a short bowel syndrome. The ECG
      changes and the precordial symptom were completely reversed by a relative short
      treatment with magnesium per os, which increased the magnesium level to low
      borderline value (1.6 mEq/1). The observation of ECG changes with precordial
      discomfort, probably linked to hypomagnesemia, suggests the need for routinary
      magnesium determinations to detect deficiency of this electrolyte, with the scope
      of improving the diagnosis and the treatment of several symptoms, otherwise
      difficult to interpret.

PMID- 9549293
TI  - [Oncologic and hematologic combined care in pediatrics].

PMID- 9549294
TI  - [Genital lichen in girls. General aspects and clinical course].
AB  - BACKGROUND: The authors re-examine the clinical aspects of infantile vulvar
      Lichen sclerosus in the light of the latest reports in the literature. METHODS: A
      group of 40 girls was studied with a mean age of 8 years old suffering from this
      pathology; 8 of the subjects had reached a prepuberal age. The group received
      different types of therapy and maintenance during a six-month and then annual
      follow-up. The results are reported correlated to the type of treatment. The
      results obtained were also evaluated depending on the age of the subject, the
      onset of puberty in some during the course of the study, the age at onset of
      disease. RESULTS: It was seen that recovery was mainly linked to aging and hence
      the evolution of puberty rather than the type of treatment, given that every drug
      has a predominantly symptomatic effect. The mean recovery time was 2.5 years
      (namely the average interval between diagnosis and puberty). CONCLUSIONS:
      Contrary to the findings reported in the literature, lesions with an early onset
      (prior to adrenarche) recovered more slowly and later.

PMID- 9549295
TI  - [Diagnosis in pediatric "allergic" patients].
AB  - BACKGROUND: A clinician who deals with allergic patients needs the help of in
      vivo and in vitro allergometric tests in order to decide difficult therapeutic
      choices. METHODS: In the section of Clinical Immunology of the Institute of
      Paediatrics (Palermo University) two allergologic tests, prick and MAST-CLA, have
      been studied retrospectively, they were performed on patients observed for
      allergic disorders over 5 years. The aim of this study was to evaluate the
      diagnostic capacity of these tests "on the field". The study population is made
      of 459 patients (age range from 6 months to 16 years) affected with asthma,
      rhinitis, presumably allergic dermatitis, association of asthma and dermatitis,
      urticaria, selected on the basis of anamnesis and clinical examination.
      Eosynophils, basophils, total IgE, specific IgE with DHS-MAST-CLA and prick tests
      (Bayropharm) for the allergens most frequently responsible of allergic disease in
      our country, have been evaluated. A double controlled assay of 1040 pairs of
      allergens with MAST-CLA has been performed. RESULTS: The agreement between prick
      and MAST appeared to be satisfactory for inhaled allergens. Eosynophils count and
      total IgE levels showed a significative difference between patients negative
      versus patients positive for at least one allergen. CONCLUSIONS: The pattern of
      the allergens most frequently positive changes with age and patients positive for
      pollens showed positivity for vegetal food allergens with a frequency higher than
      expected.

PMID- 9549296
TI  - ["Pediatric" forms of Creutzfeldt-Jakob disease (nvCJD)].
AB  - The authors propose the name of pediatric CJD disease (nvCJD) for those forms of
      this pathology which appear in childhood and adolescence (about twenty cases have
      been reported in Europe: 1996). The "pediatric form" differs both in terms of age
      ("teenagers" and also 16-year-old), but also owing to its long course (mean of 14
      to 35 months) and the early onset of psychiatric and sensory symptoms. Until a
      few years ago, discussion of a new pediatric-adolescent form of the disease (new
      variant of CJD) would have been laughable.

PMID- 9549297
TI  - [A case of congenital hemangioma of the left lower extremity].
AB  - A case of congenital hemangioma located in the lower left extremity is reported.
      The evolution and the clinical characteristics are also discussed. The
      angiogenesis theory can now explain the genesis and the evolution of hemangioma.

PMID- 9549298
TI  - [L-arginine and immunity. Study of pediatric subjects].
AB  - BACKGROUND: Nitric oxide (NO) play a pivotal role in many biological processes,
      as in the vessel tone control, the atherogenesis, the platelets aggregation and
      the immune system modulation. The physiologic precursor of NO is the L-arginine.
      Evidence exists that the L-arginine administration can stimulate immune system in
      children with recurrent infections. This clinical trial was designed to evaluate
      the effects of oral administration of L-arginine on the number of infective
      events and on the lymphocytes subsets in children suffering from airways
      recurrent infections. METHODS: Forty outpatients, 21 male and 19 female, aging
      from 2 to 13 yrs. Two balanced groups, treated for 60 days with L-arginine or a
      placebo. Evaluation criteria: number of septic episodes; number of circulating
      white blood cells, % of the lymphocytes; lymphocytes subsets. STATISTICAL
      ANALYSIS: Descriptive analysis; inference tests: chi 2; "t" test; variance
      analysis. Statistical significance: p = 0.05. RESULTS: Fifteen patients treated
      with L-arginine and five treated with placebo (p < 0.01) were free from
      infections. The percentage of CD3 and CD4 subsets significantly (p < 0.05)
      increased in the L-arginine group than in the placebo group, while the CD8 subset
      significantly decreased. The CD4/CD8 ratio raised from 1.05 +/- 0.29 to 1.51 +/-
      0.46 (p < 0.01) in the L-arginine group, from 1.12 +/- 0.16 to 1.27 +/- 0.24 in
      the placebo group. There were no side effects in both groups. CONCLUSIONS: L
      arginine seems able to increase the immune system defences and to protect against
      the airway infections.

PMID- 9549299
TI  - [On ceftriaxone and biliary pseudolithiasis].

PMID- 9549300
TI  - [Graves' disease].

PMID- 9549301
TI  - The union drama unfolds.

PMID- 9549302
TI  - U.S. physicians seek collective bargaining power.

PMID- 9549303
TI  - The hospitalist trend. A work in progress.

PMID- 9549304
TI  - Character healing: a fresh look at psychodynamic psychotherapy.
AB  - Caught between the successes of modern psychopharmacology, the requests of
      suffering patients for quick relief, and the shortsightedness of many third-party
      payers, psychodynamic psychotherapy might seem to be on the ropes. It is,
      however, thriving and providing crucial help to many individuals for whom
      medication and brief counseling are insufficient. Meanwhile, many more who could
      benefit from psychotherapy do not have an opportunity to do so. Although
      psychodynamic psychotherapy originated and developed within a medical framework,
      it has minimal visibility on the current medical scene, and many physicians have
      been provided with little meaningful information about it. This article is
      intended to give physicians a general idea of what psychodynamic psychotherapy is
      and how it works.

PMID- 9549305
TI  - Impediments to cost-effective care.

PMID- 9549306
TI  - MMA blocks bill to triple statute of limitations.

PMID- 9549307
TI  - MMA fights efforts to triple statute of limitations.

PMID- 9549308
TI  - MMA supports improved bill to address fetal alcohol syndrome.

PMID- 9549309
TI  - [Stress and alcohol: research with experimental animals].
AB  - Research on the interaction of ethanol and stress with experimental animals are
      briefly reviewed. There might be the two aspects of the interaction of stress and
      ethanol, i.e., how stress affects ethanol ingestion and response to ethanol, and
      how ethanol modifies stress response. In general, stress increases ingestion of
      ethanol in animals exposed to various stresses including electric shock,
      immobilization and psychological or emotional stresses, wherein the psychological
      or emotional factors were predominantly involved. However, in most cases, ethanol
      ingestion is increased after release from stress not during exposure to stress. A
      variety of stressful stimuli caused marked increases in the neurotransmitter
      release in many brain regions. Immobilization stress increased noradrenaline
      release in the extended brain regions in rats. These increases were significantly
      attenuated by pretreatment with ethanol in the rat amygdala and locus coeruleus,
      but not in the hypothalamus, although ethanol by itself increased noradrenaline
      release in the hypothalamus. Further, psychological stress, wherein the rats were
      given no electrical shock, but exposed to the emotional responses such as
      struggling, vocalization, jumping and defecation shown by the other electrically
      shocked rats, increased noradrenaline release preferentially in the hypothalamus,
      amygdala and locus coeruleus. Among the former two regions, stress-induced
      increases in noradrenaline release were significantly attenuated by ethanol in
      the amygdala, but not in the hypothalamus. Together with the finding that
      increases, in noradrenaline release are closely related to the provocation of
      anxiety and/or fear, ethanol, in part, reduced tension, as mentioned in the
      tension reduction hypothesis, by attenuating stress-induced increases in
      noradrenaline release in the amygdala and locus coeruleus. Moreover, ethanol,
      administered i.p. and directly through the microdialysis probe, increased
      dopamine release in the nucleus accumbens assessed by in vivo microdialysis,
      similarly as addictive drugs such as amphetamine did. This might be, in part,
      neurochemical basis for motivation of repeated drinking of ethanol.

PMID- 9549310
TI  - Changes in sympathetic and parasympathetic function in alcoholic neuropathy.
AB  - We examined sympathetic and parasympathetic function in 17 chronic alcoholics.
      The subjects were divided into 4 groups; (1) alcoholics without neurologic
      deficits, (2) alcoholics with mild neuropathy, (3) alcoholics with prominent
      neuropathy, (4) patients with alcoholic neuropathy but long abstinence. We
      measured pulsatile arterial pressure (AP) noninvasively and heart rate (HR) was
      calculated from the AP signals. The sweat response on the palm and sole were
      measured by ventilated capsular method, while the cutaneous blood flow response
      by laser Doppler flowmetry. The AP, HR, sweating and cutaneous blood flow
      response to the Valsalva maneuver were evaluated. In alcoholics with minimal and
      prominent neuropathy, a pressor (overshooting) in phase IV of the Valsalva
      maneuver were decreased significantly. The HR response (reflex bradycardia) in
      phase IV of the Valsalva maneuver was significantly decreased only in alcoholics
      with prominent neuropathy. The alcoholics with no or minimal neuropathy showed
      exaggerated sweat responses on the palm and sole. In prominent alcoholic
      neuropathy, the sweat response was greater on the palm, but diminished on the
      sole. In no or minimal neuropathy, magnitude of the blood flow response was
      markedly reduced on both sites. The low resting blood flow levels may contribute
      to the diminished response. We also evaluated pupillary light reflex and response
      to methacholine in 7 alcoholics with neuropathy by a portable infrared
      pupillometer system that can be used with personal computers. Maximum
      constriction velocity of the pupillary light reflex in patients with alcoholic
      neuropathy was slower than that in the controls. Reflex amplitude was smaller in
      the alcoholics than that in the control. However, local administration of
      methacholine did not change pupillary size and light reflex in the alcoholics
      same as the controls. The data suggest that preceding sympathetic hyperfunction
      related with distressed autonomic center is existing with sympathetic
      hypofunction involved from the sympathetic fibers, target organs and higher
      center.

PMID- 9549312
TI  - [Present status of respiratory infections in aged].

PMID- 9549311
TI  - [Genetic polymorphism of human CYP2E1: new allels detected in exons and exon
      intron junctions].
AB  - Cytochrome P450-2E1 (CYP2E1) is a major component of the microsomal ethanol
      oxidizing system (MEOS) and is also involved in the metabolism of a variety of
      foreign compounds including carcinogens. It has been shown that there is an
      interindividual variation in the expression of human hepatic CYP2E1. Gene
      environmental interactions have been suggested to account for the difference. In
      this study, we screened nine exons of the human CYP2E1 gene for detecting allelic
      variants in genomic DNA samples obtained from 115 Japanese controls, 96 Japanese
      alcoholics and 124 American control subjects. A novel missense mutation in exon 2
      (V72L) was found in Japanese controls, and another missense mutation in exon 8
      (D394G) was detected in American Caucasians. In addition, two novel silent
      mutations in exon 6 (T303T) and exon 8 (F420F) were found in Japanese controls
      and alcoholics. Especially the silent mutation in exon 8 was highly polymorphic
      among three population groups. The mutation in exon 2 (V72L) was detected only in
      Japanese controls, but not in alcoholics although it shows no significant
      difference. Gene frequency of the silent mutation in exon 8 was significantly
      higher in Japanese than American Caucasians (34.8% vs 21.0%, p < 0.02). Our data
      indicated that nucleotide replacement in the open reading frame is no major
      factor responsible for alcoholism. However, functional significance of the two
      novel missense mutations remains to be detailed.

PMID- 9549313
TI  - [Changes of pathogenic microbes in respiratory infections in aged].

PMID- 9549314
TI  - [Physiological role and dynamics of cytokines in respiratory infections].

PMID- 9549315
TI  - [Differential diagnosis of respiratory tract infections based on the symptoms and
      test results].

PMID- 9549316
TI  - [Progress on diagnostic imaging in respiratory tract infections].

PMID- 9549317
TI  - [Gene diagnosis and its significance in respiratory tract infections].

PMID- 9549318
TI  - [Primary care for respiratory tract infections].

PMID- 9549319
TI  - [New antibiotic therapy of respiratory tract infections and prevention of the
      adverse effects].

PMID- 9549321
TI  - [Therapeutic countermeasure for respiratory tract infections caused by resistant
      strains to antibiotics].

PMID- 9549320
TI  - [Selection between oral and injection routes of antibiotic therapy for
      respiratory infections based on clinical observations].

PMID- 9549322
TI  - [Treatment of respiratory tract infections associated with respiratory failure].

PMID- 9549323
TI  - [Therapeutic and preventive countermeasures for respiratory tract infections
      associated with malignancies].

PMID- 9549324
TI  - [Ideal joint clinical communication systems for therapy of respiratory tract
      infections].

PMID- 9549325
TI  - [Therapy of common cold--special reference to influenza].

PMID- 9549326
TI  - [Therapy and prevention of aspiration pneumonia].

PMID- 9549327
TI  - [Important points in therapy of pulmonary tuberculosis and atypical mycobacterium
      respiratory infections].

PMID- 9549328
TI  - [Therapy of respiratory tract infections in aged and management of their quality
      of life (discussion)].

PMID- 9549329
TI  - [Case of chronic kidney failure with thrombotic thrombocytopenic purpura due to
      miliary tuberculosis].

PMID- 9549330
TI  - [Anti-EJ antibody as diagnostic markers for a case of polymyositis].

PMID- 9549331
TI  - [Three cases of Fitz-Hugh-Curtis syndrome detected in the early stage by
      abdominal ultrasonography].

PMID- 9549332
TI  - [Present status in analysis of atopic disease genes].

PMID- 9549333
TI  - [Genetic diagnosis of cardiovascular diseases and the therapeutic application].

PMID- 9549334
TI  - [Cytomegalovirus infections and hematopoietic disorders].

PMID- 9549335
TI  - [Migraine and neurotransmitters].

PMID- 9549336
TI  - [Drug delivery system for optimizing therapeutic effects: recent trends in
      research].

PMID- 9549337
TI  - [Recent development of nucleic acid drug].
AB  - Oligonucleotides and their analogs have been utilized for the regulation of gene
      expression since mid-1970. The so-called antisense strategy has recently acquired
      its reality of the application to clinical therapeutic uses. In the course of the
      development, it has been found that nucleic acids might have broad variety of
      abilities to regulate gene expression. The abilities are classified as ribozymes,
      antigenes, decoy DNAs (or RNAs) and aptamers, and they can be applied to clinical
      uses as nucleic acid drugs in the near future.

PMID- 9549338
TI  - [Molecular design of polymer-conjugated cytokines and its application for drug
      delivery systems].
AB  - In recent years, clinical application of recombinant cytokines has been expected
      as a novel drug for various diseases. However, cytokines have generally poor
      stability in vivo, so they required of very high doses to achieve sufficient
      clinical effect. In addition, because cytokines have pleiotropic functions, they
      would cause unfavourable side-effects. Therefore an drug delivery system (DDS) is
      necessary for clinical use, which stabilizes the cytokines and potentiates only
      the expected function from other unfavorable ones in vivo. Then we performed the
      chemical modification of cytokines with water-soluble polymers to overcome such
      problems as poor stability and pleiotropic activities. This approach includes
      some advantages that decrease renal excretion rate of proteins and prevent the
      degradation by proteases. This would result in prolonging the half-lives of
      bioactive proteins and potentiating their clinical effects. Interestingly, we
      found that the polymer-conjugated cytokines, that we named hybrid-cytokines, for
      instance, polyethylene glycol-modified interleukin-6 (PEG-IL-6), were able to
      increase selectively in their function of promoting platelet production, but not
      in other unfavourable functions. This effects were suggested for a result of the
      change in the systemic distribution pattern by pegylation of proteins. In this
      review, we proposed that the DDS using hybrid-cytokines would be able to increase
      the stability and regulate the spectrum of the functions of the cytokines by
      controlling the pharmacokinetics and pharmacodynamics in vivo. This will provide
      a fundamental information enabling us to design the hybrid-proteins applicable to
      therapeutic use.

PMID- 9549339
TI  - [Individualization of drug therapy and pharmacogenetics].
AB  - This brief review discusses the relationship between genetic polymorphism of drug
      metabolizing enzyme and drug's safety and efficacy. When elimination occurs via a
      single metabolic pathway, individual differences in metabolic rates can lead to
      large differences in drug and metabolite concentrations in the blood. Genetic
      polymorphism leads to subpopulation of patients with decreased, absent or even
      increased activities of certain reactions (e.g., CYP2C19, CYP2D6, CYP2C9, N
      acetyltransferase, thiopurine methyltransferase polymorphism). The consequences
      of a genetic polymorphism include not only altered kinetics of specific drug
      substrate but idiosyncratic adverse drug reactions. Having these information will
      aid in determining dosage of certain medications to the patients with an
      inherited abnormality of drug metabolizing enzyme. Pharmacogenetics already has
      influenced therapeutics.

PMID- 9549340
TI  - [Application of ultrasound energy as a new drug delivery system].
AB  - Ultrasound is frequently used in medicine for diagnostic purposes. Recently,
      there have been numerous reports on application of ultrasound energy for
      controlling drug release or targeting. This new concept of therapeutic ultrasound
      combined with drugs has induced excitement in various areas. Ultrasound energy
      can enhance effects of thrombolytic agents as urokinase. Ultrasound emitting
      catheters are currently being developed for cardiovascular diseases. Device with
      ultrasound transducers implanted in transdermal drug patches are also being
      evaluated for possible delivery of insulin through the skin. Chemical activation
      of drugs by ultrasound energy for treatment of cancers is another new field
      recently termed as "Sonodynamic Therapy". Various examples of application of
      ultrasound for drug delivery systems are discussed.

PMID- 9549341
TI  - [Methodologies for regulation of intestinal absorption of biologically active
      peptides].
AB  - Oral bioavailability of biologically active peptides and proteins is generally
      very low because they are extensively degraded by peptidases and proteases in the
      gastrointestinal tract and impermeable through the intestinal mucosal membrane.
      Consequently, although clinical application of peptide drugs is limited to
      administration by injection, such frequent subjects the patients to considerable
      pain, and there is also possibility of the manifestation of serious side effects.
      Therefore various approaches have been examined to overcome the delivery problems
      of peptide drugs. These approaches include (1) to use additives such as
      absorption enhancers and protease inhibitors, (2) to modify the peptide molecules
      to produce prodrugs and analogs, (3) to develop an administration method for
      peptides that can serve as an alternative to oral and injection administration
      and (4) to use the dosage forms to these peptide drugs. In this paper, we
      introduce the approaches (1)-(3) and demonstrate that transmucosal absorption of
      various biologically active peptides and proteins could be improved by using
      these approaches. These approaches therefore may give us basic information to
      improve the intestinal absorption of peptide and protein drugs.

PMID- 9549342
TI  - [Improvement of drug bioavailability using protease inhibitors].
AB  - Although many proteins and peptides were produced by gene-technology, their
      administration routes are limited to be i.v. route. To increase the clinical use
      of these products, oral dosage form is required. However, in the case of oral
      administration, proteins are degraded by digestive fluid having strong protease
      activity. To decrease the protease activity, protease inhibitors are administered
      concomitantly with proteins. Aprotinin, soybean trypsin inhibitors and gel
      forming polymer such as Polycarbophil are representative protease inhibitors. Gel
      forming polymers have both protease inhibiting activity and absorption enhancing
      effect on protein/peptides. The usefulness of these protease inhibitors have been
      suggested as an additive for the oral delivery of G-CSF and vasopressin
      derivatives.

PMID- 9549343
TI  - [Improvement of intestinal absorption of peptide and protein drugs by chemical
      modification with fatty acids].
AB  - It is well known that the oral bioavailability of peptide and protein drugs is
      generally poor because they are extensively degraded by proteases in the
      gastrointestinal tract and impermeable through the intestinal mucosa. Therefore,
      various approaches have been examined to overcome the delivery problems of these
      peptides and to improve their absorption via the gastrointestinal tract. Of these
      approaches, a potentially useful approach to solve these delivery problems may be
      chemical modification of peptides and proteins to produce prodrugs and analogues.
      Thus, it is plausible that this approach may protect peptides against degradation
      by peptidases and other enzymes present at the mucosal barrier and renders the
      peptides and proteins more lipophilic, resulting in increased bioavailability.
      From these standpoints, we synthesized lipophilic derivatives of peptides and
      proteins such as thyrotropin-releasing hormone (TRH), tetragastrin (TG),
      calcitonin and insulin by chemical modification with fatty acids. The
      pharmacological activities of these derivatives were relatively high as compared
      with the native peptides. A significant increase in the intestinal absorption of
      these derivatives of peptides was observed in comparison with native peptides.
      Overall, the effects of acylation on the intestinal absorption of these peptides
      were more predominant in the large intestine than those in the small intestine.
      In addition, these derivatives were more stable than the parent peptides in
      homogenates of the various intestinal mucosae. We also examined the intestinal
      transport characteristics of TG and its acyl derivatives using Caco-2 cell
      monolayers in order to assess the contribution of enzymatic and transport
      barriers on their intestinal absorption. The degradation clearance of TG on the
      apical membrane was decreased by chemical modification with fatty acids. In
      addition, the permeability clearance of TG was improved by the acylation. On the
      other hand, the intestinal absorption of thyrotropin releasing hormone (TRH),
      which is transported by a carrier-mediated process, was also enhanced by chemical
      modification with lauric acid. In summary, this chemical modification approach
      may be useful to improve the intestinal absorption of peptide and protein drugs.

PMID- 9549344
TI  - [Enhancement of drug absorption by iontophoresis and phonophoresis and clinical
      application].
AB  - Concepts of iontophoresis and phonophoresis are described. Main factors regarding
      iontophoretic transdermal drug delivery of ionized drugs or non-ionized drugs and
      clinical applications are outlined. Iontophoretic and sonophoretic transdermal
      drug delivery has some advantages and disadvantages. However, its clinical use
      for controlled drug delivery corresponding to chronopharmacology will bring more
      benefit to patients in near future.

PMID- 9549345
TI  - [Strategies for drug delivery to the brain across the blood-brain barrier].
AB  - Designing drugs (including peptides) with greater lipophilicity are still
      effective strategy for the enhancement of the permeability across the blood-brain
      barrier (BBB), which is considered to be lipoidal membrane barrier of endothelial
      cells which have tight junctions without fenestrations. However, for the
      development of brain-specific drug delivery for neuroactive drugs, it may be
      greater promising strategy to utilize the specific influx transporters existing
      at the BBB for hexoses, amino acids, monocarboxylic acids, amines or to inhibit
      the functions of the efflux transporters such as P-glycoprotein which pumps out
      cytotoxic and/or lipophilic drugs. Attractive approach to the delivery of
      peptides is to design the peptide to be transported across the BBB via
      ologopeptide specific transporters, via insulin or transferrin receptor-mediated
      transcytosis, or via adsorptive-mediated transcytosis specific for positively
      charged peptides.

PMID- 9549346
TI  - [Transdermal therapeutic systems].
AB  - Advances in transdermal therapeutic systems (TTS) and the technology involved
      have been rapid because of the sophistications of physiology and biology on skin,
      enhancing methodology for the skin penetration of drugs, and material and polymer
      sciences on the pharmaceutical additives. In this review paper, such progress was
      introduced and the future on the TTS was augured.

PMID- 9549347
TI  - [Delivery of macromolecular drugs to the vitreous and its peripheral tissues].
AB  - We evaluated the release behavior of FITC-dextran with an average molecular
      weight of 4,400(FD4), as a model peptide drug, from poly(DL-lactic acid) (PLA)
      implant. The drug level in the vitreous and its peripheral tissues were measured
      following the implantation in the rabbit vitreous. The release profile of FD4
      from the PLA implant was biphasic; a fraction of the drug molecules incorporated
      in the polymer implant was swiftly released; then slowly or even negligibly for a
      certain period of time and finally complete bursting release probably due to bulk
      erosion of the polymer. The time-course of drug concentration in the vitreous and
      aqueous humor after implantation showed a constant level for 14 days and then
      parabola, where the highest concentration appeared around 28 days. The drug
      concentrations in the retina/ choroid was maintained a constant level for 28
      days. After an injection of FD4 in the rabbit vitreous, the drug concentration in
      those tissues approximately decreased mono-exponentially. These findings suggest
      that the present implant could be a useful carrier for delivery of macromolecular
      drugs to the vitreous and its peripheral tissues.

PMID- 9549348
TI  - [PEG-liposome in DDS and clinical studies].
AB  - The current status of newly developed polyethyleneglycol coated liposome (PEG
      liposome) were described in this review. Liposomes have demonstrated considerable
      promise as a carrier for the delivery of drugs in vivo. However, one of the
      drawback is that most liposomes intravenously injected into animals are rapidly
      removed from the blood circulation by uptake primarily in the cells of
      reticuloendothelial system (RES). It has been found that PEG-liposome are not
      readily taken up by the macrophages in the RES and hence stay in the circulation
      for a relatively long period of time. Pharmacokinetic analysis and therapeutic
      studies with tumor bearing mice revealed that PEG-liposomes have considerable
      potential as drug carriers for cancer therapy. Elevated liposome accumulation has
      been found in the tumor bearing mice model system. Results from clinical studies
      with doxorubicin encapsulated into PEG-liposomes (DOXIL) in AIDS-related Kaposi's
      sarcoma revealed an increased therapeutic efficacy compared to free-drug. These
      new formulations of long-circulating liposomes (PEG-liposome) offer the
      development of immunoliposomes with both long survival times in circulation and
      target recognition being retained in vivo. Fab'-PEG-immunoliposome was newly
      designed to gain long-circulating enough to extravasate to the targeted solid
      tumor in vivo. An ultimate goal of Fab'-PEG-immunoliposome is the incorporation
      of a fusogenic molecules that would induce fusion of liposome following their
      binding to the target cells or their internalization by endocytosis. Such
      liposomal formulations should be useful for endocytotic internalization of
      plasmid DNA and other bioactive materials.

PMID- 9549349
TI  - [Application of monoclonal antibody for drug delivery system--missile therapy for
      cancer].
AB  - Clinical applications of monoclonal antibody for selective delivery of anticancer
      drug, toxin and radioisotope were reviewed. The difficulties in preparation and
      clinical application of chemoimmunoconjugate were pointed out. Also the
      difficulties of immunotoxin in clinical trial due to its high toxicity had been
      discussed and it is assumed that development of blocked ricin may overcome many
      problems related to toxicities. Clinically most advanced immunoconjugate seems to
      be radioimmunoconjugate. Among three types of immunoconjugates preparation of
      radioimmunoconjugate is easiest and some promising clinical trials were
      introduced in this review.

PMID- 9549350
TI  - [Targeting of anticancer drug using intelligent polymers].
AB  - To fabricate the drug targeting system, it is very effective to combine passive
      targeting with intelligent polymeric system such as temperature-responsive
      polymers. We have been studying the passive targeting of anticancer drug bonded
      with or physically trapped in polymeric micelle derived from poly (ethylene
      oxide) (PEO) and poly (aspartic acid) block copolymer. On the other hand, Poly(N
      isopropylacrylamide) (PIPAAm) is known to be a thermo-responsive polymer which
      has lower critical solution temperature (LCST, 32 degrees C). PIPAAm shows the
      reversible phase transition above and below LCST. Attempts to apply thermo
      responsive drug carriers were made to enhance the site-specificity of polymeric
      micelle. Namely, novel type of polymeric micelle were prepared from block
      copolymers comprising N-isopropylacrylamide (IPAAm)-hydrophobic polymers. This
      temperature responsive micelles were expected to induce selective accumulation
      controlled by temperature modulation.

PMID- 9549351
TI  - [Targeting technology utilizing magnetic microparticulate system for cancer
      therapy].
AB  - Organ level-targeting of anticancer drugs or other relating stimuli to tumor
      tissues and their circumstances is important in cancer therapy. The successful
      targeting results in the greater antitumor effect and the lower numerous side
      effects. Application of a magnet from the outside of body is a useful tool to
      increase the targeting efficacy. In this review paper, targeting technology
      utilizing magnetic microparticulate system for cancer therapy was introduced and
      the future on the magnetic targeting system was augured.

PMID- 9549352
TI  - [Transferrin conjugated PEG-liposomes as intracellular targeting carrier for
      tumor therapy].
AB  - For the purpose of intracellular targeting carrier by systemic administration,
      PEG-liposomes conjugating transferrin (TF) at the distal ends of PEG chain were
      newly prepared. Biodistribution of TF-PEG liposome was examined in the colon 26
      bearing mice. TF-PEG liposome were prolonged in the circulation and highly
      accumulated into the tumor tissue. After extravasation, TF-PEG liposome retains
      the specific binding ability to tumor cell surface. Uptake of TF-PEG liposome was
      examined by electron microscopy. TF-PEG liposome was localized at the cell
      surface, coated pits and endosome. These results show TF-PEG liposome was bound
      and internalized by endocytosis. Such liposomes should be useful for
      intracellular targeting carrier at the way of systemic administration.

PMID- 9549353
TI  - [Pharmaceutical and pharmacological development of antitumor prostaglandins].
AB  - Antitumor Prostaglandins such as delta 12PGJ2 and delta 7PGA1 possess a cross
      conjugated dienone unit and exhibit unique antitumor effect. Lipid microshere
      (w/o type emulsion) was selected as pharmaceutical formulation because of
      physicochemical properties of prostaglandin. 13,14-Dihydro-15-deoxy-delta 7-PGA1
      methyl ester (TEI-9826) were selected as a candidate for clinical trial. In a rat
      and mouse serum in vitro, TEI-9826 rapidly metabolized to 13,14-dihydro-15-deoxy
      delta 7-PGA1 (TOK-4528), but TOK-4528 is stable as well as delta 12PGJ2. Lipid
      microshere containing TEI-9826 at the content of 5 mg/ml exhibited administration
      route and schedule dependent antitumor effect in vivo using Colon 26 bearing
      mouse model, which suggested that duration of serum concentration was important
      for antitumor effect. One of the antitumor mechanism of antitumor PG might be an
      induction of the cyclin-dependent kinase inhibitor p21. PPAR gamma also might be
      important. New type homogenizer, high pressure jet flow type homogenizer was
      developed in the study of antitumor prostaglandin.

PMID- 9549354
TI  - [Controlled release using temperature-responsive poly(N-isopropylacrylamide)
      gel].
AB  - Poly (N-isopropylacrylamide) (PNIPAAm) gels were found to undergo discontinuous
      swelling-deswelling changes in response to a limited alteration in external
      temperatures. By utilizing such as thermosensitive characteristic of the PNIPAAm
      gel, controlled drug release was studied extensively. Drug release profiles were
      well established in connection with the temperature dependence of swelling ratio
      for the gel. The thermal regulation of the swelling degree of the gel made it
      possible for us to design several ways for performing a unique drug release
      profile such as a "pulsatile" or "on-off" release of indomethacin. Attempts to
      develop a more excellent drug release system have being made through studies of
      molecular design and synthesis for PNIPAAm-based thermosensitive gels.

PMID- 9549356
TI  - [Design and application of oral sustained-release anticancer drug--a new oral
      dosage form of cisplatin].
AB  - As compared to the conventional standard chemotherapy of solid cancer such as
      lung, biochemical modulation (BCM) therapy has been proven to have a good
      therapeutic efficiency. BCM therapy uses the low dose and low infusion rate of
      anti-cancer drug. To increase of the QOL of cancer patients, oral BCM therapy is
      needed. For this purpose, two kinds of new oral sustained-release cisplatin
      preparations were developed, micro-porous CDDP capsule made of ethylcellulose(EC)
      and CDDP-EC-stearic acid solid dispersion. After oral administrations of these
      preparations, serum CDDP levels were maintained over 0.2 microgram/ml for 24h.
      Experimental therapy using P815 tumor cells transplanted mice suggested the
      usefulness of CDDP solid dispersion preparation.

PMID- 9549355
TI  - [Design and development of controlled release of drugs from injectable
      microcapsules].
AB  - Monolithic microcapsules were designed and developed for controlled release of
      leuprorelin for one month following a single injection. Copoly (DL
      lactic/glycolic) acid (PLGA) of copolymer ratio of 75/25 and average molecular
      weight of 14,000 was suitable for achieving steady serum leuprorelin levels in
      rats and dogs for 4 weeks. The clinical efficacy of these injectable
      microcapsules of leuprorelin has been widely proved for prostate cancer,
      endometriosis, and other sex hormone dependent diseases in about sixty countries.
      The interaction between the basic functional group of the drug and the carboxylic
      end group of PLGA was found to be the most important factor in preparing the
      microcapsules with a small initial burst, as shown with thyrotropin releasing
      hormone (TRH) and a water-soluble GPIIb/IIIa antagonist (TAK-029).

PMID- 9549357
TI  - [Drug delivery system (DDS) for the use of antisense oligodeoxynucleotide
      phosphorothioate in controlling gene expression].
AB  - Synthetic antisense oligodeoxynucleotide phosphorothioates (ODNs) are widely used
      as therapeutic tools in various in vitro and in vivo systems. Here, we applied
      ODNs to inhibit viral gene expression. Human T-cell leukemia virus type I (HTLV
      I) is a retrovirus, and is closely linked to adult T-cell leukemia (ATL), HTLV-I
      associated myelopathy/tropical spastic paraparesis(HAM/TSP), and other HTLV-I
      associated diseases. With an attempt to control viral replication in vitro, ODNs
      to HTLV-I tax gene were synthesized and applied. In addition, 1,2-dioleoyloxy-3
      (trimethylammonio) propane, DOTAP as a drug delivery system, was exploited to
      increase the cellular uptake of ODNs. Combination of ODNs and DOTAP was more
      effective to suppress viral antigen expression than ODNs only. Therefore this
      combination method may be useful in clinical trials for HTLV-I-associated
      diseases.

PMID- 9549358
TI  - [Drug delivery systems in gene therapy].
AB  - The use of nonviral vectors is an attractive in vivo gene delivery strategy that
      is simpler and lacks some risks inherent in viral systems. Liposomes and receptor
      mediated polycation systems are promising carriers for delivery and expression of
      plasmid DNA encoding genes into the target cells. Many barriers need to be
      overcome for successful in vivo DNA delivery using these carrier systems. Various
      factors such as the extent of DNA condensation, particle size of the DNA complex,
      route of administration, stability against nucleases, target sites, in vivo
      disposition, binding to cell surface receptor and internalization, intracellular
      trafficking affect the in vivo gene delivery and expression. This chapter will
      focus on the current status and perspectives of the plasmid DNA delivery systems
      for in vivo gene therapy.

PMID- 9549359
TI  - [Study of T cell-directed gene transfer for a patient with ADA deficiency].
AB  - We have been undertaking the gene therapy for a 6 year-old boy with ADA
      deficiency and performed 11 cycles of the infusion of the peripheral T cells
      transduced with retroviral vector LASN since August 8th 1995. The percentage of
      the peripheral blood lymphocytes carrying the transduced ADA gene has remained
      stable at 10% to 20% since the 4th infusion. ADA enzyme activity in his
      circulating T cells increased to levels comparable to 1/3 of a heterozygous
      carrier individual and was associated with increased T lymphocytes counts and
      improvement in both humoral and cellular immune function. The results obtained in
      this clinical study support the usefulness of T lymphocyte-directed gene transfer
      in the treatment of ADA deficiency.

PMID- 9549360
TI  - [Gene delivery using adeno-associated (AAV) vectors].
AB  - Gene transfer vectors based on the replication-defective adeno-associated virus
      (AAV) are emerging as promising vehicles for gene therapeutic approaches for the
      neurologic disease, cystic fibrosis and cancers. AAV vectors have been used to
      efficiently transduce genes into cells in vitro and in vivo. However, transduced
      recombinant AAV vectors are integrated into human chromosomes. Thus we have
      discussed that the review about the AAV vectors and transduction, and reported
      the results used AAV vectors for expression of ribozyme.

PMID- 9549361
TI  - [Cationic liposomes in gene delivery].
AB  - Cationic liposomes have been extensively explored as gene delivery vector for
      several reasons. It is because disadvantages of viral vectors include risk of
      replication, possible immunogenicity, and the difficulty of obtaining a large
      quantity of viral vectors. Currently, a variety of cationic components for
      liposome formulations have been developed. The components are broadly divided
      into two classes based on the chemical structure of hydrophobic moieties: long
      aliphatic (saturated or unsaturated) hydrocarbons and cholesterol ring. A variety
      of hydrophilic moieties also include tertiary amines, ammonium salt and spermine.
      The role of liposomes is to condense DNA to form complexes with high affinity to
      cell surfaces where possible fusion or destabilization of the membrane and/or
      endocytosis are involved. However, at present, little structure-activity
      relationships are known. Some vectors are on clinical trials approved by NIH.

PMID- 9549362
TI  - [Gene introduction into animal tissues by fusogenic liposomes].
AB  - The future success of gene therapy relies largely upon the development of ideal
      gene-transfer vehicles (vectors) that can efficiently and stably introduce and
      express therapeutic genes into non-dividing tissue cells. We have developed a
      fusogenic liposome that can deliver the encapsulated DNA into the cytoplasm
      through fusion with the cell membrane. For targeting the DNA into the nucleus, we
      attend to lambda phage particles that encapsulate up to 48 kbp DNA in their small
      head (55 nm in diameter). When a strong NLS signal is attached on the surface of
      the phage head by recombinant DNA technology, the particles efficiently
      accumulate in the nucleus. Reconstitution of the ideal gene-transfer system
      through a detailed analysis of biological phenomena is discussed.

PMID- 9549363
TI  - [Intracellular gene delivery by polymer micelle vectors].
AB  - This review paper deals with the development of novel vector system for gene and
      antisense oligonucleotides. The system is based on the self-association of
      poly(ethylene glycol)-poly(L-lysine) block copolymer with DNA to form polyion
      complex micelles with unimodel size distribution in the range of 50-100 nm. DNA
      molecules are compactly assembled into the core of the micelle, surrounding with
      the dense corona of poly(ethylene glycol). High resistance to nuclease attack was
      demonstrated for micellized DNA in the serum-containing medium, indicating the
      potential of micelle vector system to stabilize DNA in physiological condition.
      Significant gene expression was confirmed by luciferase assay using 293 cell-line
      for these micelle vector systems with slightly cationic character.

PMID- 9549364
TI  - [Gene delivery into human cancer cells via transferrin receptor].
AB  - At present, vectors widely used for gene transduction are retroviruses and
      adenoviruses. However, the transduction using these vectors are primarily
      conducted ex vivo. The direct in vivo gene delivery method to target tumor cells
      are required. Trials to augment specificity of gene targeting to tumor cells have
      been in progress including approaches to use modified virus particles by gene
      technology instead of wild type particles or to take advantage of ligand-receptor
      or antibody-antigen systems by allowing vector DNAs to bind these ligand and
      antibodies. Transferrin receptor (TfR) is widely distributed on actively
      proliferating cells and is therefore an appropriate target for in vivo gene
      delivery into those cells. We developed a simple method to conjugate biotinylated
      double-stranded DNA to biotinylated Tf via streptavidin and demonstrated
      successful transduction of the conjugate into TfR-positive human cancer cells.
      The present method may provide a novel technique for gene transduction, which may
      be used especially to transfer various DNA vectors into cells specifically
      expressing TfR, in vivo as well as in vitro.

PMID- 9549365
TI  - [Targeting delivery of therapeutic genes using monoclonal antibody; immunogene
      approach].
AB  - We are developing the "immunogene" system for the targeted delivery of
      therapeutic genes. The immunogene system utilizes the EGF receptor-mediated
      endocytosis. The Fab fragment of monoclonal antibody B4G7 against human EGF
      receptor was conjugated with polylysine to form an "Fab immunoporter", which
      forms an affinity complex with DNA. The transfection efficiency of Fab immunogene
      was approximately 10-fold higher than the Lipofectin. Gene transfer of HSV-tk
      gene into A431 tumor cells with Fab immunoporter was successful and the
      subsequent treatment with ganciclovir induced remarkable suicide effects
      conferring 1000-fold higher drug sensitivity. Thus, the immunogene system could
      be useful as a gene transfer vehicle targeting the EGF receptor-hyperproducing
      tumor cells.

PMID- 9549366
TI  - [Drug delivery system in cardiovascular drugs].
AB  - Various drug delivery systems are available when cardiovascular drugs are used.
      Various kinds of receptor inhibitors such as beta blockade or angiotensin II
      receptor inhibitor are frequently used in the daily cardiovascular clinic.
      Several different routes of drug administration exist. Conventional tablet or its
      liquid spray by sublingual or lingual administration is rapidly absorbed and
      specified oral tablet or transdermal patch for maintaining longtime is slowly
      absorbed from the digestive tract or skin. Some drugs have different type of
      tablets for obtaining different pharmacodynamics. Nifedipine has 3 kinds of
      tablets showing short, long and very long-time effect. Recent advance in drug
      delivery system makes possible to administer the drug to the small local area
      through stent or balloon catheter at the coronary interventional therapy.

PMID- 9549368
TI  - [Drug delivery system for diabetes].
AB  - Long-term intensified insulin therapy composing of multiple insulin injection and
      self-blood glucose monitoring enables glycemic control of insulin-requiring
      diabetics. For reducing inconvenience of this therapy, several delivery route of
      insulin are under investigation. Nasal administration of insulin aerosol
      effectively controlled insulin-dependent diabetics for up to 6 months because its
      high bioavailability and rapid absorption. By means of ionophoresis or ultrasound
      approach, insulin was shown to be absorbed transdermally. Polymer containing
      modified insulin and immobilized enzyme could increase insulin release against
      hyperglycemia. These new approach of insulin delivery might increase convenience
      of insulin administration.

PMID- 9549367
TI  - [Drug delivery system for the treatment of osteoporosis].
AB  - The number of agents for the treatment of osteoporosis has increased over the
      past few years allowing more and more differentiated therapy. Calcitonin, vitamin
      D3, bisphosphonate, estrogen, vitamin K2 and calcium are administered for the
      treatment of osteoporosis in Japan. The purpose of drug delivery system (DDS) is
      to provide a practical approach to increasing efficacy and minimizing side
      effects of the drugs. In fact by the development of DDS, topical administration,
      prodrug and targeting therapy are used in the treatment for osteoporosis. It is
      well known that calcitonin in susceptible to proteolysis in the intestine. So,
      calcitonin must be given intramuscular or subcutaneous injection for therapy. DDS
      of calcitonins is studying in many routes of administration, such as nasal,
      transdermal, ocular, oral, bronchial, rectal and vaginal.

PMID- 9549369
TI  - [Drug delivery system for infectious diseases].
AB  - Various types of antimicrobial agents have been evolved to inhibit growth of or
      to kill different microorganisms. In recent years, encapsulation of antimicrobial
      agents in lipid formulations has been a popular practice in research work related
      to drug delivery system, although most of the studies are based primary on animal
      models. The recent developments of lipid formulations of anti-infectious drug
      (antibiotics, antifungals, and antiviral agents) with longer half-life opens new
      therapeutic avenues in treating infections. The passive targeting of liposomes to
      the sites of infection is of great value with respect to clinical application.
      Liposome entrapment can exchange their pharmacokinetics and, hence reduce their
      toxicity.

PMID- 9549370
TI  - [New drug delivery systems for the therapy of bronchial asthma].
AB  - Inhalation therapy gives us ideal topical therapy for the airway diseases without
      significant major side-effects. As new century approaches, a major goal for
      asthma therapy will be to provide more effective therapeutic drugs to prevent
      airway inflammation and its spasmus. It is also important to produce excellent
      inhalant devices that are easy to use and do not contain substances that are
      harmful to the environment. Future inhalers should target the drug to the correct
      sites in the airways and thus enable optimal therapeutic effects to be achieved.
      There are many exciting new developments available in this field. And we should
      finally obtain special therapeutic drugs to prevent the process to the sudden
      onset of asthmatic death.

PMID- 9549371
TI  - [Anti-HIV drugs and drug delivery system].
AB  - A number of candidate drugs for therapy of HIV-1 infection which show significant
      activity against the virus in vitro were reported; however, many of them have
      been dropped from drug development due to (i) insufficient intracellular
      activation in certain human target cells (particularly in case of nucleoside
      reverse transcriptase inhibitors), (ii) poor pharmacokinetic profiles, or (iii)
      intolerable in vitro and/or in vivo toxicities. To circumvent some of these
      problems, certain drug delivery systems have been applied and several candidate
      drugs including two novel nucleoside reverse transcriptase inhibitors, abacavir
      and adefovir, have acquired favorable properties in the clinical setting. This
      paper reviews several avenues for developing prodrugs of anti-HIV-1 agents to
      overcome their inherent limitations.

PMID- 9549372
TI  - [Monoclonal antibodies as an immunotherapy of rheumatoid arthritis].
AB  - Rheumatoid arthritis(RA) is a chronic, deforming and destructive arthritis of
      unknown etiology. For the medical treatment of RA, NSAID has been the first
      choice of drug. Recently it has been known that early use of DMARD may result in
      clinical remission. Understanding of the pivotal role of cytokines and adhesion
      molecules for the rheumatoid joint destruction enabled us to target these
      cytokines and molecules as therapeutic measures. Monoclonal antibodies were
      produced against the cytokines and adhesion molecules such as IL-1, IL-6, IL-6R,
      TNF-alpha, as well as CD4 molecules. Clinical use of these monoclonal antibodies
      was found to be effective for rheumatoid arthritis. However these therapeutic
      measures have several disadvantages such as transient efficacy and side effect.

PMID- 9549373
TI  - [Drug delivery system of anti-inflammatory and anti-rheumatic drugs].
AB  - Anti-rheumatic drugs such as nonsteroidal anti-inflammatory drugs,
      glucocorticoids, and disease modifying anti-rheumatic drugs are valuable
      medications for patients with rheumatoid arthritis available for physicians now.
      This review provides a practical approach for increasing efficacy and minimizing
      adverse response of some of these drugs by the development of drug delivery
      system.

PMID- 9549374
TI  - [Ulcerative colitis--colon delivery of 5-aminosalicylic acid].
AB  - Ulcerative colitis, Crohn's disease and hemorrhage colitis are typical example of
      colon specific diseases. The targeting of the drugs for these colon specific
      diseases was attempted by a new technology, where ethylcellulose (EC) was used as
      pharmaceutical material. Especially, pressure-controlled colon delivery capsule
      (PCDC) made of EC is a unique system. PCDC was prepared by coating the inner
      surface of gelatin capsule with water-insoluble polymer, EC. By adjusting the
      coating thickness of EC membrane to be approximately 40 microns, colon delivery
      of dug were obtained both in beagle dogs and human volunteers. PCDC containing 5
      ASA was prepared and was administered orally to beagle dogs. After
      administration, 5-ASA appeared into the systemic circulation at 3-5 h which
      corresponds to the colon arrival time confirmed with sulfasalazine.

PMID- 9549375
TI  - [Molecular modeling of immunological proteins by bioinformatics].
AB  - The antibody combining site is composed of six complementarity determining
      regions (CDRs), whose typical structures have been classified as "canonical
      structures" except CDR-H3, depending upon the segment lengths and the positions
      of specific amino acid residues in the segments. Using the method of structural
      bioinformatics, we have proposed a novel classification of the CDR-H3 structures,
      and revealed several remarkable relationships between their sequences and the
      loop conformations. Based upon the canonical structures and our new rules,
      structural models of antibodies have been built in order to understand the
      molecular basis of antigen recognition. Another new computational method of
      almost exhaustive conformational search is introduced for future applications.

PMID- 9549376
TI  - [Human immunodeficiency virus and AIDS in terms of reverse transcriptase and
      molecular evolution].
AB  - Human immunodeficiency virus type 1 (HIV-1) evolves rapidly in the host. The
      computer analysis of the HIV-1 genome has shown that the mutation manner is
      dependent on oligonucleotide sequences (in particular, six bases long); thus HIV
      1 adaptively evolves. The six-base-long interaction between template-primer
      oligonucleotide and the reverse transcriptase (RT) has been revealed by the
      crystal structure of RT, in vitro termination assay of plymerization, and
      hydroxyl radical footprint analysis. It has been thought that AIDS is caused by
      the large numbers of HIV-1 quasispecies yielded by the adaptive and rapid
      evolution in the host. However, the slow evolution and the high levels of viral
      RNA in the progressive HIV-1 infected individuals (progressives) were recently
      reported; in contrast, the adaptive and rapid evolution and the low viral-RNA
      levels were reported in the non-progressives. This suggests that the
      physiological environment, e.g. pH and dNTP balance, in which RT works in the
      progressives is different from that in the non-progressives.

PMID- 9549377
TI  - [Imaging of myocardial perfusion and metabolism with positron emission
      tomography].
AB  - Positron emission tomography (PET) has been providing new information in the
      diagnosis and the pathophysiological assessment of heart diseases. The PET
      tracers commonly used in Japan are 13N-ammonia, 18F-fluorodeoxyglucose (FDG) for
      imaging of myocardial perfusion and metabolism, respectively. Measurement of
      regional myocardial blood flow by 13N-ammonia dynamic PET scan and a compartment
      model analysis is applied to the functional estimation of coronary stenotic
      lesions and the detection of perfusion abnormalities in hypertrophic heart
      diseases, familial hyperchlesterolemia and other diseases with possible
      microvascular lesions. 18F-FDG is commonly used to differentiate ischemic but
      viable tissue from myocardial scar in coronary artery disease and also used to
      detect cardiac tumor and the cardiac involvement in sarcoidosis. In addition to
      these two tracers, 11C-acetate is now expected to provide the clinical analysis
      of pathophysiology of heart failure by estimating the efficiency of energy
      conversion of the heart into external work.

PMID- 9549378
TI  - [Helicobacter pylori, gastric pathology, and histopathological diagnosis].

PMID- 9549379
TI  - [Chronic gastritis. Guidelines and minimum diagnostic criteria. Italian Digestive
      System Pathologists Group].

PMID- 9549380
TI  - [A variety of mediastinal bronchogenic cyst: the broncho-alveolar cyst].
AB  - Congenital bronchogenic cysts are usually located in the mediastinum or develop
      as intrapulmonary cysts. Gross examination of excised bronchogenic cysts shows
      them to be unilocular; histologically, these lesions are characterized by the
      presence of respiratory-type pseudostratified epithelium as well as small islands
      of cartilage and seromucinous glands. We report a case of a mediastinal
      bronchogenic cyst having pulmonary parenchyma within the cyst wall. The rarity of
      our case, the pathological and clinical features and the embryological
      development of bronchogenic cysts are briefly discussed.

PMID- 9549381
TI  - [Lymph node inflammatory pseudotumor. Description of a case].
AB  - A case of inflammatory pseudotumor of lymph node in a 56-year-old man is
      described. The awareness of this benign reaction pattern is of great importance
      for differential diagnosis with many nodal lesions.

PMID- 9549382
TI  - [Lipoleiomyoma of the uterus].
AB  - The presence of fatty tissue in the myometrium is anomalous; this alteration has
      been interpreted either as a lipomatous degeneration or as a metaplasia of smooth
      muscle cells or, still, as a real neoplasm, frequently associated with a
      leiomyoma, the so-called lipoleiomyoma. The observation of a case of
      lipoleiomyoma stimulated us to ascertain the real incidence of this lesion which
      is commonly considered to be rare. We examined 620 single or multiple uterine
      leiomyomas with extensive sampling of all the areas suspected to contain fatty
      tissue islands. Five times out of seven the presence of fat cells in a leiomyoma
      resulted to be a true lipoleiomyoma. It has thus been possible to ascertain the
      incidence of lipoleiomyoma versus uterine leiomyomatosis (0.8%). Futhermore we
      observed a prevalence in menopause, an association with multiple leiomyoma and a
      preferential onset in the subserosa. The pathogenesis of this lesion, which can
      be fully ascribed to a mixed, benign, heterologous, mesenchymal neoplasm, is
      briefly discussed.

PMID- 9549384
TI  - [Why physicians should read books (medical)?].

PMID- 9549383
TI  - [Sarcoid-like hepatic granulomas, associated with gastric neoplasia. Description
      of a case].
AB  - Giant cell granulomas in liver biopsies is a relative common finding. Among the
      many causes of granulomatous lesions of the liver primary biliary cirrhosis and
      sarcoidosis are the most frequently diagnosed. On the other hand sarcoid-like
      granulomatous reaction can be encountered associated to malignant tumours.
      Purpose of the present paper is to describe a case of a sarcoid-like reaction of
      the liver associated to gastric adenocarcinoma. The patient was a 66 yr old man
      who underwent gastrectomy for a signet-ring cell adenocarcinoma. Pathological
      anamnesis was unremarkable. Liver function tests were within normal limits. Chest
      x ray was normal. A liver biopsy was performed during surgery as the liver
      presented an irregular surface. On histology giant cell granulomas with sarcoid
      like features were seen in the hepatic parenchyma. Same reaction was present in
      the perigastric lymph nodes. The patient died immediately after surgery due to
      massive pulmonary embolism. No autopsy was performed. Among the possible
      diagnoses primary biliary cirrhosis, sarcoidosis and paraneoplastic sarcoid-like
      granulomatous reaction were considered. Primary biliary cirrhosis and sarcoidosis
      were excluded on the basis of the past clinical history of the patient, that was
      unremarkable; furthermore liver function tests performed preoperatively were
      within normal ranges. Thus paraneoplastic sarcoid-like reaction involving the
      liver was regarded as the most likely diagnosis.

PMID- 9549385
TI  - [Hypnotic drugs in a population. Prescriptions by the specialist and the general
      practitioner].
AB  - The aims of our survey were to estimate the prevalence of hypnotic drug
      prescription in a representative sample of population in 5 cities of Northern
      Italy and to analyse the pattern of prescription of these drugs by general
      practitioners (GPs) and psychiatrists. The data were collected with the
      collaboration of pharmacists working in 145 pharmacies. All consecutive patients
      presenting a prescription for a hypnotic drug were interviewed by the pharmacists
      during a two-week period. The pharmacists interviewed 7744 consecutive patients.
      The highest prevalence of prescriptions for hypnotic drugs was found in the
      elderly and in women. The majority of prescriptions were for benzodiazepines
      (BDZ), with lorazepam and triazolam accounting for about 50% of the total
      prescriptions. Short-acting and ultra-short-acting BDZ were more frequently
      prescribed for sleep induction by GPs than by psychiatrists. Approximately 73% of
      subjects reported that they had been taking the prescribed drug for one year or
      more. The high proportion of long-term BDZ users may be a consequence of the
      short period surveyed, which produced data weighted toward long-term consumption.
      Our data, however, do not permit to establish whether long-term use is
      appropriate from a clinical point of view or is the consequence of a physical
      dependence. We must be aware that this practice needs to be studied more
      accurately, with the aim to assess the risk/benefit ratio of long-term BDZ use.

PMID- 9549386
TI  - [Therapy of refractory rheumatoid arthritis. Cyclosporin and methotrexate
      combination].
AB  - Rheumatoid arthritis (RA) is a chronic multisystemic disease affecting mainly the
      joints and characterised by a poor prognosis. In a four month open study we
      evaluated the efficacy and tolerability of a combination therapy in 14 patients
      with active and refractory RA (non responsive to MTX or CsA monotherapy). After
      three pulses of methyl-prednisolone (125 mg/die i.v. for 3 days), at day the 4
      patients received methotrexate (MTX 15/mg/week p.os) and cyclosporine (CsA 3
      mg/kg/day p.os). At the end of treatment period, patients had a statistically
      significant improvement in the tender-joint count (Ritchie Index) in the swollen
      joint count and in the pain as recorded on a 100-mm visual-analogue scale.
      Following the criteria of the American College of Rheumatology for response to
      treatment in RA, 6 patients (60%) met these criteria, whereas 2 had a worsening.
      We could not detect any clear difference in serological parameters (ESR, CRP and
      Hb levels) between the beginning and the end of the therapy. A significant
      difference in the score of edema/joint effusion was documented at the RM
      analysis. Side-effects were not substantially increased as compared to MTX or CsA
      in single therapy. Combination therapy with CsA and MTX seems to be a safe and
      effective treatment for patients with active and refractory RA.

PMID- 9549387
TI  - [Combined drug therapy in recent-onset rheumatoid arthritis. Evaluation after 1
      year of treatment].
AB  - The aim of our study is to evaluate the efficacy and safety of a combination
      therapy with hydroxycloroquine, gold sodium thiomalate and methotrexate in
      patients affected by recent onset active rheumatoid arthritis. Twenty-five
      patients (6 men e 19 women, average age 46.2 +/- 12.2) were enrolled in this
      study and 18 of them have been treated for 1 year with the three above-mentioned
      drugs at optimal doses. Drug toxicity was carefully monitored. Clinical and
      hematochemical parameters of efficacy were evaluated every three months.
      Radiographic joint study was performed at the beginning and at the end of the
      study. Seven patients dropped out, six of them for side effects, due to
      hydroxycloroquine in 1 case and to gold sodium thiomalate in 5 cases; 1 patient
      withdrew his consent. No life-threatening or irreversible adverse reactions were
      observed. The eighteen patients who completed the one year trial presented a
      remarkable improvement of clinical and hematochemical parameters. In only 1 case
      one erosion appeared at the end of the study. In conclusion, the combination
      therapy with hydroxycloroquine, gold sodium thiomalate and methotrexate seems to
      be effective and burdened by an acceptable level of toxicity.

PMID- 9549388
TI  - High dose dexamethasone as first line therapy of multiple myeloma? A case report.
AB  - The authors describe a case of multiple myeloma in which a complete remission was
      obtained by treatment with high dose dexamethasone. This was the only therapy
      suitable for the patient because of heavy myelosuppression due to disease and to
      one course of conventional treatment with melphalan and prednisone. Further
      trials are needed to evaluate the usefulness and safety of this treatment as
      first line therapy, especially in the elderly, with pancytopenia and bad
      performance status.

PMID- 9549389
TI  - [Microscopic polyangiitis. A case report].
AB  - We describe a 36 year old male patient affected by microscopic polyangiitis; he
      was treated with corticosteroic and cyclophosphamide pulses obtaining clinical
      improvement and remission and acute flogistic index normalization. The peculiar
      aspect is a stable remission during a four years follow up; the only relapse was
      controlled with low dose of corticosteroids.

PMID- 9549390
TI  - [Prevention of cancer: epidemiology and prospects].

PMID- 9549391
TI  - [Relationship between polymyalgia rheumatica and temporal arteritis].

PMID- 9549393
TI  - [Nuclear cardiology toward the year 2000].

PMID- 9549392
TI  - [Fever of unknown origin in rheumatology].
AB  - Fever occurs frequently in several rheumatic disorders, and remains a diagnostic
      and therapeutic challenge to the rheumatologist in spite of the great advances
      made in the fields of medical diagnosis and technology. It can be the initial
      symptom of a rheumatic disease, but it can also be the expression of a disease
      flare, of an infectious complication, of a secondary neoplasm or be of iatrogenic
      origin. The pathogenesis of fever in rheumatic diseases is still quite unclear;
      however, recently IL-1, IL-6 and other endogenous pyrogens, such as Tumor
      necrosis factor, have been shown to play a pivotal role in causing pyrexia during
      inflammatory conditions. In the presence of longstanding fever of unknown origin,
      it is mandatory to carry out a number of selected appropriate examinations with
      the patient's informed consent. The aim of this study was to review the frequency
      and the characteristics of fever at the onset and in the course of a number of
      rheumatic diseases, such as chronic inflammatory arthropathies, connective tissue
      diseases, reactive arthritis and dysmetabolic arthropathies. Finally, we have
      reviewed the features of fever during arthritis complicating non-rheumatic
      diseases and during adverse reactions related to drugs that are widely prescribed
      for the treatment of rheumatic disorders.

PMID- 9549394
TI  - [Quantification of left-to-right shunt in atrial septal defect using oximetry,
      isotopes, and Doppler echocardiography. Is there a method of reference?].
AB  - INTRODUCTION: Determination of pulmonary to systemic blood flow ratio (QP/QS) is
      considered to be important for the management of patients with atrial septal
      defect. The QP/QS provides information on shunt severity and is usually
      determined by three methods: oximetry, first-pass radionuclide angiocardiography
      and Doppler echocardiography. The aim of the present study was to assess the
      accuracy and concordance level of these three methods in QP/QS quantification in
      atrial septal defects. PATIENTS AND METHODS: Sixty-four adult atrial septal
      defects patients in whom QP/QS was determined by these three methods with a 6
      month interval were studied. Nuclear and echocardiographic post-surgical studies
      were repeated in 36 patients. RESULTS: QP/QS values determined by the three
      techniques had a low correlation between them: oximetry (r = 0.52; SEE = 0.74);
      radionuclide angiocardiography (r = 0.40; SEE = 0.79) and Doppler
      echocardiography (r = 0.72; SEE = 0.57). Radionuclide angiocardiography
      underestimated QP/QS > 3 (-0.61 +/- 1.21; p < 0.01). Only in 33% of studies there
      concordance (differences < 0.5) among the three methods and in 58% between two
      methods. Right ventricular dilatation and tricuspid regurgitation influenced
      radionuclide accuracy. Nevertheless, the correlation between this technique and
      echocardiography was satisfactory when the 36 post-surgical were included (r =
      0.75); both techniques agreed in the diagnosis of the two cases with residual
      post-surgical shunt. CONCLUSIONS: Inter-method disparity in QP/QS quantification
      is high and no method can be used as a gold standard; clinical decisions
      therefore based on QP/QS quantification by one technique alone are ill-advised.

PMID- 9549395
TI  - [Determination of ejection fraction and left ventricular fraction using isotopic
      ventriculography and bidimensional echocardiography. Comparison with contrast
      ventriculography].
AB  - OBJECTIVES: The aim of this study was to determine the correlation and agreement
      between the values of left ventricular ejection fraction and volumes assessed by
      echocardiography and radionuclide ventriculography with the results obtained by
      contrast angiography, as well as the variability of each method in these
      measurements. PATIENTS AND METHODS: In a group of 59 patients with a first acute
      myocardial infarction we have determined left ventricular ejection fraction and
      volumes by two-dimensional echocardiography, equilibrium radionuclide
      ventriculography and contrast angiography initially and six months after
      myocardial infarction. We also assess the variability in the determinations in
      these three methods. RESULTS: We found significant correlations in ejection
      fraction and volumes by radionuclide ventriculography and echocardiography with
      contrast angiography. The correlation was higher in ejection fraction and end
      systolic volume by radionuclide ventriculography (r = 0.88 and r = 0.73) than by
      echocardiography (r = 0.55 and r = 0.63; p < 0.01), whereas the correlation of
      end-diastolic volume was moderate by both methods (r = 0.58 and r = 0.47),
      without significant differences. The agreement between contrast angiography and
      radionuclide ventriculography was higher, with narrower limits of agreement than
      between contrast angiography and echocardiography in ejection fraction as well as
      in ventricular volumes. We have found high and significant correlations between
      two determinations by each method in all parameters, although they were higher in
      ejection fraction by contrast angiography (r = 0.96) and radionuclide
      ventriculography (r = 0.98) than by echocardiography (r = 0.70; p < 0.01). The
      limits of agreement were always wider in echocardiography, narrower in contrast
      angiography and the narrowest in radionuclide ventriculography, showing its
      superior reproducibility. CONCLUSIONS: In this group of myocardial infarction
      patients, the variability in the measurements was lower by radionuclide
      ventriculography than by echocardiography, this could be the reason for overall
      better results found in correlation and agreement between radionuclide
      ventriculography and contrast angiography than between echocardiography and
      contrast angiography in the assessment of left ventricular ejection fraction and
      volumes.

PMID- 9549396
TI  - [Impact of the correction of the attenuation in myocardial perfusion image with
      SPECT].
AB  - BACKGROUND: The aim of this study was to assess the effect of attenuation
      correction on gender differences in normals and to evaluate its effect on the
      size and severity of lateral wall perfusion defects in patients with circumflex
      artery disease. MATERIAL AND METHODS: Tomographic myocardial perfusion imaging
      with and without attenuation correction was performed on 32 patients with
      circumflex artery stenosis and compared with patients with less than 5%
      likelihood of coronary disease. Images were acquired with a triple headed scanner
      and reconstructed using an iterative algorithm and re-sliced in the short axis
      plane. Regional count densities were measured on selected short axis slices from
      the base to the apex in both patients and normals. RESULTS: All attenuation
      corrected images were found to be more uniform than the non attenuation corrected
      images on the patients with less than 5% likelihood of coronary artery disease.
      The coefficient of variation was 12.5% for non attenuation corrected images
      versus 9.9% for attenuation corrected images (p < 0.0001). When female and male
      segmental count distributions were compared, significant differences were found
      which were resolved after attenuation correction. In patients with circumflex
      artery stenosis, the anterolateral and lateral count densities were lower at all
      levels with attenuation corrected images with an increasing difference from base
      to apex. CONCLUSIONS: The use of attenuation correction results in a greater
      uniformity in normals and an improved estimation of extent and severity of
      perfusion defects in the territory of the circumflex artery.

PMID- 9549397
TI  - [Study of myocardial viability using single-photon emission computed tomography
      with 201-thallium and re-injection in 4 series (early and late images].
AB  - OBJECTIVE: The present study was designed to determine whether 24-hour imaging
      after thallium reinjection or imaging obtained shortly after reinjection provides
      better results regarding reversibility of fixed perfusion defects observed in
      conventional stress-redistribution imaging. PATIENTS AND METHODS: We studied 24
      patients undergoing stress-redistribution thallium tomography with fixed defects
      (15 exercise, 6 adenosine, 3 dobutamine). All patients had coronary angiography
      and 17 a history of myocardial infarction. After obtaining the redistribution
      images, 1 mCi thallium was injected at rest, and images were acquired at 30
      minutes and 24 hours after reinjection. The tomograms obtained were divided into
      12 segments and analyzed quantitatively. RESULTS: Of the 190 abnormal segments on
      the stress images, 53 (28%) demonstrated improved thallium uptake on
      redistribution images and 137 had persistent defects. Shortly after reinjection,
      33 (24%) segments had improved thallium uptake and 104 had persistent defects, 29
      (28%) of which showed further improvement in the 24-hour study. In patients with
      myocardial infarction, of the 36 fixed severe defects, 9 (25%) had improved
      thallium uptake shortly after reinjection, increasing activity from 36 +/- 10% to
      53 +/- 8%, and 22 (61%) defects improved at 24 hours, increasing activity from 37
      +/- 8% to 56 +/- 6%. Therefore, 13 irreversible segments in the short-term study
      after reinjection were reversible on 24-hour images. CONCLUSION: These data
      indicate that 24-hour imaging after thallium reinjection provides better results
      regarding reversibility of fixed perfusion defects observed in conventional
      stress-redistribution imaging than imaging obtained shortly after reinjection.

PMID- 9549398
TI  - [Evaluation of myocardial viability using perfusion cardiac SPECT. 201-thallium
      rest/redistribution, 201-thallium rest/reinjection and technetium 99m tetrofosmin
      rest/postnitrates].
AB  - INTRODUCTION AND OBJECTIVES: It has been demonstrated that nitrate administration
      enhances the detection of myocardial viability in thallium-201 and technetium-99m
      sestamibi myocardial perfusion studies. The aim of this study was to assess the
      influence of nitrate administration on technetium-99m tetrofosmin myocardial
      uptake in patients with coronary artery disease and left ventricular dysfunction.
      PATIENTS AND METHODS: Twenty eight patients with coronary artery disease,
      previous myocardial infarction and left ventricular ejection fraction < 40%
      underwent, within 48 hours, rest/postnitroglycerin (0.4 mg sublingually)
      technetium-99m tetrofosmin single photon emission tomography (SPET), comparing
      these results with that of thallium-201 rest/redistribution SPET in 13 patients
      (first group) and with that of thallium-201 rest/reinjection SPET in the other 15
      patients (second group). Tomograms based on the 3 spatial planes were divided
      into 15 segments and regional tracer uptake was quantitatively analysed.
      Viability was defined as presence of tracer uptake > or = 50% of peak activity.
      RESULTS: The percentage of peak activity at rest or after nitrate administration
      of technetium-99m tetrofosmin correlated, with that of thallium-201, at rest and
      after redistribution or reinjection (r = 0.8; p < 0.001). On resting technetium
      99m tetrofosmin studies 167 of the 420 segments that were analysed had < 50% of
      peak activity. 14.5% of these segments showed reversibility after nitrate
      administration, with an increase in 99mTc-tetrofosmin uptake from 45 +/- 5% to 55
      +/- 4% of peak activity (p = 0.001), in the first group, and from 40 +/- 9% to 57
      +/- 9% of peak activity (p = 0.003), in the second group. Overall agreement
      between rest/postnitroglycerin technetium-99m tetrofosmin SPET studies and
      rest/redistribution or rest/reinjection thallium-201 SPET studies, regarding the
      presence of myocardial viability, was 87% and 90%, respectively. All except one
      reversible segments on tetrofosmin studies after nitrates had viability criteria
      on thallium studies. CONCLUSIONS: Nitrate administration at rest enhances the
      detection of myocardial viability using technetium-99m tetrofosmin SPET,
      correlating with viability criteria observed on thallium studies. It represents a
      simple and useful technique in the assessment of myocardial viability.

PMID- 9549399
TI  - [Study of active myocardial damage in children with suspected myocarditis using
      antimyosin monoclonal antibodies (AMMoAb-111In)].
AB  - BACKGROUND: The study with monoclonal antimyosin antibody-111In has proved to be
      useful in the detection of the myocardial damage present in different processes.
      There is active myocardial damage and specific antimyosin uptake in myocarditis,
      as both experimental and clinical trials have shown. In experimental models the
      evolution of myocardial damage has been studied, where a parallelism between the
      histological changes of the myocardial damage and the evolution on the antimyosin
      uptake has been found. In clinical myocarditis it is difficult to do an
      histological follow up of the inflammatory process, and therefore the evolution
      of myocardial damage present in myocarditis is unknown. The antimyosin antibody
      images allow a non-invasive study of this evolution. OBJECTIVES: a) to study with
      monoclonal antimyosin antibody-111In, the myocardial damage present regarding the
      disease evolution in children with suspected clinical diagnosis of myocarditis;
      b) to evaluate the evolution of the active myocardial damage reflected on the
      changes on the monoclonal antimyosin antibody-111In uptake. METHODS: A study with
      monoclonal antimyosin antibody-111In was carried out on 43 children, 16 males and
      27 females with a median age of 39 months (SD 48 m; range: 2-167) with suspected
      diagnosis of acute myocarditis defined as the presence of congestive cardiac
      failure or severe ventricular arrhythmia with less than 12 months of evolution.
      The image evaluation was done visually and through the heart to lung ratio.
      Twenty of these patients were also followed up with antimyosin antibody scan for
      a period of 19 +/- 9 months, and 3.8 +/- 1.7 studies were performed on them in
      this time. RESULTS: The prevalence of positive myocardial uptake was 83.72%.
      There is a negative correlation (r = -0.352; p < 0.02) between the evolution time
      of the process and the heart to lung ratio: patients studied before two months,
      have a higher heart to lung ratio and greater prevalence of positive studies than
      those studied later (heart to lung ratio 2.09 vs 1.74; p = 0.013; 90% vs 69.2%).
      Of the patients followed up with antimyosin antibody scans, 6 showed a clinical
      relapse which increased their heart to lung ratio. The other 14 showed an
      progressive decrease of the heart to lung ratio reaching normality in 14 +/- 6
      months. CONCLUSIONS: a) the uptake intensity of monoclonal antimyosin antibody
      111In, as a reflection of the myocardial damage, depends on the disease evolution
      time, as in the first two months is when the major damage happens; b) the uptake
      intensity slowly decreases, tending to normality around the 14th month, although
      this evolution may be altered by the appearance of relapses.

PMID- 9549400
TI  - [Evaluation of cardiac sympathetic innervation with 123I-metaiodobenzylguanidine
      in patients with diabetes mellitus].
AB  - OBJECTIVES: To evaluate the usefulness of iodine-123 metaiodobencylguanidine
      (123I-MIBG) in the study of the cardiac autonomic neuropathy in insulin-dependent
      diabetic patients, by means of: a) analysis of heart to mediastinic ratio and
      tomographic images with 123I-MIBG; b) comparison with conventional non-invasive
      cardiac reflex test, and c) analysis of left ventricle ejection fraction.
      POPULATION AND METHODS: Ten patients submitted for cardiac evaluation with 123I
      MIBG were compared with a control group of 11 patients. In both groups we
      excluded the presence of coronary pathology by means of an exercise test. We
      carried out planar and SPECT studies, using 123I-MIBG, and the calculation of the
      ejection fraction by equilibrium ventriculography. RESULTS: The uptake of 123I
      MIBG in diabetic patients was significantly smaller than the control group in the
      calculated index (heart to mediastinic ratio: 1.64 +/- 0.20 vs 2.00 +/- 0.26; p <
      0.001; SPECT index: 44.87 +/- 8.37 vs 55.54 +/- 3.96; p < 0.001). In polar images
      we noted a more reduced uptake in the diabetic group in the inferior wall (p =
      0.020). Patients with cardiac sympa-thetic dysinnervation demonstrated less
      uptake in both indexes (p < 0.05 and 0.005, respectively), essentially in the
      inferior wall and in basal and medium territories (p < 0.05). No differences in
      respect to the ejection fraction parameter were found. CONCLUSIONS: Despite the
      small sample population, insuli-dependent diabetic patients in show a significant
      reduction of the uptake of 23I-MIBG, more accentuated in the base. Scintigraphy
      using 123I-MIBG can be an approach to investigate the pattern and the natural
      history of the sympathetic innervation in these patients.

PMID- 9549401
TI  - [Identification of the ischemic origin of dilated myocardiopathy using positron
      emission tomography].
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study was to differentiate ischemic
      from nonischemic dilated cardiomyopathy with positron emission tomography. This
      differentiation is necessary to establish an adequate treatment, and it is often
      difficult with non-invasive diagnostic procedures. METHODS: Ten patients with an
      echocardiographic diagnosis of dilated cardiomyopathy who had undergone coronary
      angiography were selected. The presence or absence of angiographic coronary
      lesions was used to define the ischemic (n = 6) and the nonischemic group (n =
      4). The ejection fraction was depressed in both groups, with no significant
      differences found. A perfusion study with 13N-ammonium and a metabolic imaging
      with 18F-florodeoxyglucose were performed on each patient. The images were
      quantitatively and qualitatively analysed, defining three criteria: accumulation
      defect (areas with activity under 50% of the maximal radioactivity), degree of
      heterogeneity, and match of images with both tracers. To determinate the degree
      of heterogeneity, nine segments on the three standard tomographic planes were
      studied. Based on the following heterogeneity features: irregular borders,
      coexisting different degrees of accumulation, and patched accumulation, a score
      ranging from 0 to 3 points was assigned to these segments. To analyse the
      radioactivity defects and the matching of studies with both tracers, the
      accumulation defects or the accumulating surface were outlined on a
      midventricular level coronal plane. RESULTS: The ischemic group has contrary to
      the nonischemic one, wider perfusion (0.26 +/- 0.21 vs 0.00) and metabolism
      defects (0.38 +/- 0.30 vs 0.06 +/- 0.09; p < 0.05). The degree of heterogeneity
      is significantly higher in the nonischemic group, either in perfusion (14.5 +/-
      8.38 vs 2.5 +/- 1.04; p < 0.05) or in metabolism studies (15.5 +/- 3.31 vs 2.33
      +/- 1.50; p < 0.005). Assigning wide defects and homogeneous accumulation to
      ischemic cardiomyopathy, and absence of defects and heterogeneous accumulation to
      nonischemic cardiomyopathy, the aetiology of the disease was identified in 9 of
      the 10 cases in the perfusion study and 100% of them with the metabolism imaging.
      CONCLUSIONS: Positron emission tomography allows to identify the aetiology of
      dilated cardiomyopathy, either with coronary perfusion or with myocardial glucose
      metabolism studies. Thus, only one of both PET studies could be used. Ischemic
      cardiomyopathy is characterised by wide defects and homogeneous radioactivity,
      and the nonischemic one by the absence of defects and heterogeneous accumulation
      of the tracer.

PMID- 9549402
TI  - Prions--tri-dimensional carriers of biological information. A bridge between
      biology and physics?

PMID- 9549403
TI  - Role of a transcription factor (CREB) in memory processes.
AB  - Memory storage includes a short-term phase (STM) which requires the
      phosphorylation of pre-existing proteins, and a long-term phase (LTM) which needs
      the novel synthesis of RNA and proteins. Cyclic AMP and a specific transcription
      factor (cAMP response element binding protein or CREB) play a central role in the
      formation of LTM in aplysia, drosophila and mice. Following its phosphorylation
      by protein kinase A, CREB binds to the enhancer element CRE which is located in
      the upstream region of cAMP-responsive genes, thus triggering transcription. Some
      of the newly-synthesized proteins are additional transcription factors that
      ultimately give rise to the activation of late response genes, whose products are
      responsible for the modification of synaptic efficacy leading to LTM. In aplysia,
      CREB activation has been interfered with by microinjection of CRE containing
      oligonucleotides into cultured neurons. Under these conditions LTM is blocked
      while STM remains unchanged. In drosophila, CREB function has been disrupted
      using a reverse genetic approach. Thus, LTM has been specifically blocked by the
      induced expression of a CREB repressor isoform, and enhanced by the induced
      expression of an activator isoform. In mouse, the role of CREB has been confirmed
      by behavioural analyses of a knock-out line with a targeted mutation in the CREB
      gene. In these mutants, learning and STM are normal, whereas LTM is disrupted. On
      the whole, the data suggest that encoding of long term memories involve highly
      conserved molecular mechanisms.

PMID- 9549404
TI  - A structuralist theory of evolution reconsidered.
AB  - The structuralist theory of evolution is reconsidered in the light of new
      discoveries. According to this theory, the evolutionary potentialities are in the
      genotype (a hierarchically ordered set of interacting elements) and manifest
      themselves in the course of morphogenesis in association with changes in the
      environment. It is demonstrated that this theory is in fact the development of a
      long philosophical tradition, in which Darwin and Neo-Darwinism did not
      participate. New discoveries in the field of molecular cytogenetics confirm the
      ideas of evolutionary potentiality and hierarchical genotypic ordering. It is
      demonstrated that gene regulation can manifest itself in association with
      instabilities of the morphogenetic field and the attainment of a new equilibrium;
      this change could be connected with changes in the environment, but has nothing
      to do with natural selection.

PMID- 9549405
TI  - Asialoglycoprotein (ASGP) receptors induced by apoptosis. Their
      immunohistochemical localization in neonatal rat hepatocytes.
AB  - Immunohistochemical detection of asialoglycoprotein (ASGP) receptors has been
      performed on neonatal rat hepatocytes in primary cultures, incubated with TGF
      beta, TNF alpha and retinoic acid. These substances account for the increase in
      the rate of apoptosis of the cell cultures and for the increase of the expression
      of ASGP receptors. Both modifications are higher at 24 hours of incubation.

PMID- 9549406
TI  - [Diversity of inwardly rectifying K+ channels; their regulations and functions].

PMID- 9549407
TI  - [Chemistry and biology of peroxynitrite].

PMID- 9549408
TI  - [Structure of heparin/heparan sulfate for regulation of activities of fibroblast
      growth factor].

PMID- 9549409
TI  - [RNA editing in transfer RNAs of metazoan mitochondria].

PMID- 9549410
TI  - [Gene organization and genetic defect of bilirubin-glucuronosyl transferase].

PMID- 9549411
TI  - [Biological functions of ceramide glucosylation].

PMID- 9549412
TI  - [Function of LCR-binding protein Bach1 as an architectural transcription factor].

PMID- 9549413
TI  - [Analysis of homologous DNA recombination in a chicken B lymphocyte line, DT40].

PMID- 9549414
TI  - Causes of unintentional deaths from carbon monoxide poisonings in California.
AB  - The purpose of this study was to determine the annual number and incidence of
      unintentional deaths from carbon monoxide (CO) poisonings in California and to
      identify specific factors that caused or contributed to the deaths. Unintentional
      CO deaths in California over a ten-year period (1979 to 1988) were identified
      from the database of the California Master Mortality File and coroners'
      investigation reports. Factors associated with unintentional CO deaths were
      determined based on the information from the investigation reports. The annual
      number of unintentional CO deaths varied from 27 to 58 over the ten years
      examined, with an average annual death incidence of 1.7 x 10(-6). Death rates
      were high among males and African-Americans. Alcohol appeared to be a factor in
      31% of the cases. The types of combustion sources associated with unintentional
      CO deaths were: heating or cooking appliances; motor vehicles; charcoal grills
      and hibachis; small engines; and camping equipment. Factors associated with
      unintentional CO deaths interact in a complex way. To reduce the rate of
      unintentional CO deaths effectively, joint efforts involving several prevention
      methods are suggested.

PMID- 9549416
TI  - Nitric oxide and septic shock. From bench to bedside.
AB  - Refractory hypotension with end-organ hypoperfusion is an ominous feature of
      inflammatory shock. In the past fifteen years, nitric oxide (a diffusible, short
      lived product of arginine metabolism) has been found to be an important
      regulatory molecule in several areas of metabolism, including vascular tone
      control. Vascular endothelial cells constitutively produce low levels of nitric
      oxide that regulate blood pressure by mediating adjacent smooth-muscle
      relaxation. In an inflammatory shock state, cytokines, like interleukin-1 and
      tumor necrosis factor-alpha, induce a separate, high-output form of the enzyme
      that synthesizes nitric oxide in both endothelial and smooth-muscle cells. The
      ensuing high rates of nitric oxide formation result in extensive smooth-muscle
      relaxation, pressor refractory vasodilation, and--ultimately--shock. The concept
      of the pathogenesis of inflammatory shock explains many limitations of current
      therapies and may foster the development of new interventions to mitigate the
      effects of nitric oxide overproduction in this syndrome.

PMID- 9549415
TI  - Use of medical informatics to implement and develop clinical practice guidelines.
AB  - Clinical practice guidelines have enormous potential to improve the quality of
      and accountability in health care. Making the most of this potential should
      become easier as guideline developers integrate guidelines within information
      systems and electronic medical records. A major barrier to such integration is
      the lack of computing infrastructure in many clinical settings. To successfully
      implement guidelines in information systems, developers must create more specific
      recommendations than those that have been required for traditional guidelines.
      Using reusable software components to create guidelines can make the development
      of protocols faster and less expensive. In addition, using decision models to
      produce guidelines enables developers to structure guideline problems
      systematically, to prioritize information acquisition, to develop site-specific
      guidelines, and to evaluate the cost-effectiveness of the explicit incorporation
      of patient preferences into guideline recommendations. Ongoing research provides
      a foundation for the use of guideline development tools that can help developers
      tailor guidelines appropriately to their practice settings. This article explores
      how medical informatics can help clinicians find, use, and create practice
      guidelines.

PMID- 9549417
TI  - Noninvasive ventilatory support--saving a life without intubation.

PMID- 9549418
TI  - Intravenous amiodarone for treating acute life threatening arrhythmias.

PMID- 9549419
TI  - Emergency department management of falls in the elderly.

PMID- 9549420
TI  - Fosphenytoin in the emergency department.

PMID- 9549421
TI  - Adult sexual assault examination.

PMID- 9549422
TI  - Treatment of deep venous thrombosis with low molecular weight heparins.

PMID- 9549423
TI  - gamma-Hydroxybutyric acid poisoning.

PMID- 9549424
TI  - Limited bedside ultrasound imaging by emergency medicine physicians.

PMID- 9549425
TI  - The placenta and cultural values.

PMID- 9549426
TI  - Zygomycotic gangrenous cellulitis in a patient with non-insulin dependent
      diabetes mellitus.

PMID- 9549427
TI  - Administration of a neuromuscular blocking agent and a narcotic agent mimicking
      posterior urethral valves.

PMID- 9549428
TI  - Immunizations for international travelers.
AB  - Each year more than 45 million Americans travel abroad for work or pleasure, and
      over 20 million of these travel to rural areas or developing countries. While the
      major medical risks of international travel are often exaggerated, the incidence
      of minor illness is not. Persons going to Asia, Africa, or Latin America for one
      month run a 65% to 75% chance of becoming ill, although only 1% will require
      hospitalization. The two most common illnesses that affect travelers, which do
      have immunizations and are often overlooked by physicians, are influenza and
      hepatitis A. The risk of illness to the traveler varies by health and age status,
      by the region to be visited, by the time of year, and by the length of the
      journey. Immunization advice for the traveler, therefore, is complicated and is
      best approached in a systematic manner. This article outlines six steps to sound
      immunization advice. These steps include ascertaining the traveler's special
      individual needs, routine immunization status, and routine travel immunization
      status, as well as the entry requirements for the country to be visited,
      geographically indicated vaccines, and immunizations as indicated for extended
      stays abroad.

PMID- 9549430
TI  - Ethics and economics. Antagonists or allies in making health policy?

PMID- 9549431
TI  - [The chemical structure of new substance as the metabolite of baicalin and time
      profiles for the plasma concentration after oral administration of sho-saiko-to
      in human].
AB  - Baicalin (BG) is one of the major components of Sho-Saiko-To. We found a new
      substance as the metabolite of BG in human plasma after oral administration of
      Sho-Saiko-To. The metabolite was identified as baicalein 6-O-sulfate (BS) by
      comparing its retention time in HPLC and electrospray ionization mass spectra
      (ESI-MS)/MS methods with that of an authentic sample. Time profiles for the
      plasma concentrations of BS and BG after oral administration of Sho-Saiko-To (EK
      9) at a daily dose (6 g), were investigated in 14 healthy male volunteers. The
      determination for the concentrations of BS and BG in human plasma was developed
      by the HPLC method using electrochemical detector (ECD). Each 1 ml of the plasma
      specimen was used for the solid phase extraction. The calibration curves of BS
      and BG showed a good linearity between 5 and 300 ng/ml. The quantitative limits
      of BS and BG in human plasma were 5 ng/ml. Using this method, BS was detected
      after 1 h, reached a maximum level at 5 h and then decreased to the level less
      than the quantitative limit after 36 h, and the plasma level of BS showed a
      slight peak at 24 h. BG was detected after 1 h, reached a maximum level at 5 h
      and then decreased to the level less than the quantitative limit after 36 h, and
      the plasma level of BG showed two peaks at 12 h and 24 h.

PMID- 9549429
TI  - The clinician's approach to the management of headache.
AB  - Headache is a ubiquitous complaint, yet it is one that often elicits anxiety in
      both patients and physicians. When a patient presents with headache, the
      clinician must answer the following questions: (1) Is the headache "worrisome"
      (secondary to underlying disease)? (2) If the headache is benign, what type is
      it? (3) How is the acute headache best treated? and (4) How may future headaches
      be prevented? The following review is intended to aid primary care physicians in
      answering these questions.

PMID- 9549432
TI  - [Synthesis and antiulcer activity of N-2-(2-hydroxy-2-phenyl)ethyl-N"
      (methanesulfonyl)guanidine analogue of ranitidine. Development of a new antiulcer
      agent T-593].
AB  - A series of the aryl-substituted N'-2-(2-hydroxy-2-phenyl)ethyl derivatives of N"
      methanesulfonyl-N-2-((5-dimethylaminomethyl or 5-methylaminomethyl)
      furfurylthio)ethylguanidine have been synthesized as potential antisecretory and
      mucosal protective antiulcer agents. The synthetic routes involves, at the last
      stage, the reaction of 2-hydroxy-2-phenylethylamines with N-2-(furfurylthio)
      ethyl-N'-methanesulfonyl-S-methylisothiourea or its O-phenylisourea counterpart.
      The primary screening test to assess the inhibitory activity of the synthetic
      compounds on histamine-induced gastric acid secretion was carried out in
      anesthetized rats by the lumen-perfusion technique of Ghosh and Schild and also
      by the pylorus-ligated preparation method. The best profile of histamine H2
      antagonist activity was much better than that of the prototype ranitidine, and
      obtained with N'-(2-(2-hydroxy-2-(4-hydroxyphenyl)) ethyl-N"-methanesulfonyl-N-2
      (5-(methylaminomethyl)furfurylthio)et hylguanidine (12f), which was also
      characterized by enhancing the gastric mucosal blood flow in rabbits as observed
      by the thermoelectric method. This compound 12f, designated as T-593,
      significantly inhibited the formation of the indomethacin-induced gastric lesions
      in rats; 3.5-fold more potent than ranitidine, but 4-fold less active than
      famotidine. On the other hand, T-593 and famotidine displayed comparable
      activities in healing the acetic acid-induced gastric ulcer with and without the
      dosing of indomethacin. Additional notable features of T-593, as determined in
      rats, are that its protective effect on the hemorrhagic shock-induced lesion
      under the prior dosing of histamine is ca. 10- and 2-fold greater than ranitidine
      and famotidine, respectively, and that a decrease in the gastric mucosal blood
      flow caused by a partial blood-withdrawal is more strongly recovered with T-593
      than with famotidine. These experimental results suggest that the antiulcer
      efficacy of T-593 can be explained by its dual activities: antisecretion of
      gastric acid and, more importantly, protection of gastric mucous membrane.

PMID- 9549433
TI  - The latest skinny on fat.

PMID- 9549434
TI  - Treating cardiac arrests on airlines.

PMID- 9549435
TI  - Can an old drug prevent restenosis after PTCA?

PMID- 9549436
TI  - Guidelines for users of diet pills.

PMID- 9549437
TI  - Hormone therapy versus statins for cholesterol reduction.

PMID- 9549438
TI  - Calcium channel blockers and breast cancer.

PMID- 9549439
TI  - My doctor says that I have both heartburn and angina. How can I tell the
      difference?

PMID- 9549440
TI  - I am diabetic and have a hard time controlling my blood sugar. I take two types
      of diabetes pills, twice a day. I had a five-way bypass last spring and would
      like to know what I should eat.

PMID- 9549441
TI  - I'm 79 years-old and had a triple bypass about 10 years ago. I took to heart your
      advice to lower my LDL cholesterol. With my doctor's support, I started daily
      doses of lovastatin (Mevacor) and cholestyramine (Prevalite). After five weeks,
      my LDL cholesterol was 87, and my total cholesterol was 164. So, how long should
      I pursue such aggressive therapy?

PMID- 9549442
TI  - Corticosteroids in rheumatoid arthritis.

PMID- 9549443
TI  - Proteases as prognostic markers in cancer.

PMID- 9549444
TI  - Interrupting the sympathetic outflow in causalgia and reflex sympathetic
      dystrophy.

PMID- 9549445
TI  - Refugee children.

PMID- 9549446
TI  - Europe's health research: getting the right balance.

PMID- 9549447
TI  - Putting the rest cure to rest--again.

PMID- 9549448
TI  - AIDS drug scandal in South Africa continues.

PMID- 9549449
TI  - The effects of postnatal health education for mothers on infant care and family
      planning practices in Nepal: a randomised controlled trial.
AB  - OBJECTIVES: To evaluate impact of postnatal health education for mothers on
      infant care and postnatal family planning practices in Nepal. DESIGN: Randomised
      controlled trial with community follow up at 3 and 6 months post partum by
      interview. Initial household survey of study areas to identify all pregnant women
      to facilitate follow up. SETTING: Main maternity hospital in Kathmandu, Nepal.
      Follow up in urban Kathmandu and a periurban area southwest of the city.
      SUBJECTS: 540 mothers randomly allocated to one of four groups: health education
      immediately after birth and three months later (group A), at birth only (group
      B), at three months only (group C), or none (group D). INTERVENTIONS: Structured
      baseline household questionnaire; 20 minute, one to one health education at birth
      and three months later. MAIN OUTCOME MEASURES: Duration of exclusive breast
      feeding, appropriate immunisation of infant, knowledge of oral rehydration
      solution and need to continue breast feeding in diarrhoea, knowledge of infant
      signs suggesting pneumonia, uptake of postnatal family planning. RESULTS: Mothers
      in groups A and B (received health education at birth) were slightly more likely
      to use contraception at six months after birth compared with mothers in groups C
      and D (no health education at birth) (odds ratio 1.62, 95% confidence interval
      1.06 to 2.5). There were no other significant differences between groups with
      regards to infant feeding, infant care, or immunisation. CONCLUSIONS: Our
      findings suggest that the recommended practice of individual health education for
      postnatal mothers in poor communities has no impact on infant feeding, care, or
      immunisation, although uptake of family planning may be slightly enhanced.

PMID- 9549450
TI  - Meta-analysis of short-term low dose prednisolone versus placebo and non
      steroidal anti-inflammatory drugs in rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether short-term, oral low dose prednisolone (< or = 15
      mg daily) is superior to placebo and non-steroidal anti-inflammatory drugs in
      patients with rheumatoid arthritis. DESIGN: Meta-analysis of randomised trials of
      oral corticosteroids compared with placebo or a non-steroidal anti-inflammatory
      drug. SETTING: Trials conducted anywhere in the world. SUBJECTS: Patients with
      rheumatoid arthritis. MAIN OUTCOME MEASURES: Joint tenderness, pain, and grip
      strength. Outcomes measured on different scales were combined by using the
      standardised effect size (difference in effect divided by SD of the
      measurements). RESULTS: Ten studies were included in the meta-analysis.
      Prednisolone had a marked effect over placebo on joint tenderness (standardised
      effect size 1.31; 95% confidence interval 0.78 to 1.83), pain (1.75; 0.87 to
      2.64), and grip strength (0.41; 0.13 to 0.69). Measured in the original units the
      differences were 12 (6 to 18) tender joints and 22 mm Hg (5 mm Hg to 40 mm Hg)
      for grip strength. Prednisolone also had a greater effect than non-steroidal anti
      inflammatory drugs on joint tenderness (0.63; 0.11 to 1.16) and pain (1.25; 0.26
      to 2.24), whereas the difference in grip strength was not significant (0.31; 
      0.02 to 0.64). Measured in the original units the differences were 9 (5 to 12)
      tender joints and 12 mm Hg (-6 mm Hg to 31 mm Hg). The risk of adverse effects
      during moderate and long term use seemed acceptable. CONCLUSION: Prednisolone in
      low doses (< or = 15 mg daily) may be used intermittently in patients with
      rheumatoid arthritis, particularly if the disease cannot be controlled by other
      means.

PMID- 9549451
TI  - Effects of the Heartbeat Wales programme over five years on behavioural risks for
      cardiovascular disease: quasi-experimental comparison of results from Wales and a
      matched reference area.
AB  - OBJECTIVE: To assess the net 5 year effects of intervention of a community based
      demonstration project, the Heartbeat Wales programme, on modifiable behavioural
      risks for prevention of cardiovascular disease. DESIGN AND SETTING: Quasi
      experimental design comparing results from two independent cross sectional
      population surveys conducted in 1985 and 1990 in Wales and a matched reference
      area in north east England. SUBJECTS: Random, stratified samples of people aged
      18-64 years (18,538 in 1985 and 13,045 in 1990) in Wales and in north east
      England (1483 and 4534, respectively). INTERVENTION: A coordinated range of
      activities for heart health promotion in Wales entailing public education
      campaigns along with supportive policy and infrastructure change. In the
      reference area no additional community heart health promotion was planned, though
      considerable activity did take place, "contaminating" the reference area. MAIN
      OUTCOME MEASURES: Fifteen self reported behavioural indicators relating to
      dietary choice, smoking, frequency of exercise, and weight. RESULTS: Positive
      changes (for health) in behavioural outcomes were observed among the population
      in Wales, including a reduction in reported smoking prevalence and improvements
      in dietary choice. There was no net intervention effect for the programme over
      and above observed change in the reference area. CONCLUSIONS: No definite
      conclusions can be drawn concerning the efficacy of the programme in terms of
      behavioural outcomes. With hindsight, the difficulties of evaluating such a
      complex multifaceted intervention were underestimated. Further debate on the most
      appropriate methods for assessing the effectiveness of community based health
      promotion programmes is called for.

PMID- 9549452
TI  - Risk factors for coronary artery disease in non-insulin dependent diabetes
      mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23)
AB  - OBJECTIVE: To evaluate baseline risk factors for coronary artery disease in
      patients with type 2 diabetes mellitus. DESIGN: A stepwise selection procedure,
      adjusting for age and sex, was used in 2693 subjects with complete data to
      determine which risk factors for coronary artery disease should be included in a
      Cox proportional hazards model. SUBJECTS: 3055 white patients (mean age 52) with
      recently diagnosed type 2 diabetes mellitus and without evidence of disease
      related to atheroma. Median duration of follow up was 7.9 years. 335 patients
      developed coronary artery disease within 10 years. OUTCOME MEASURES: Angina with
      confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial
      infarction. RESULTS: Coronary artery disease was significantly associated with
      increased concentrations of low density lipoprotein cholesterol, decreased
      concentrations of high density lipoprotein cholesterol, and increased
      triglyceride concentration, haemoglobin A1c, systolic blood pressure, fasting
      plasma glucose concentration, and a history of smoking. The estimated hazard
      ratios for the upper third relative to the lower third were 2.26 (95% confidence
      interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to
      0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for
      haemoglobin A1c, and 1.82 (1.34 to 2.47) for systolic blood pressure. The
      estimated hazard ratio for smokers was 1.41 (1.06 to 1.88). CONCLUSION: A quintet
      of potentially modifiable risk factors for coronary artery disease exists in
      patients with type 2 diabetes mellitus. These risk factors are increased
      concentrations of low density lipoprotein cholesterol, decreased concentrations
      of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia,
      and smoking.

PMID- 9549453
TI  - Association between plasma concentrations of plasminogen activator inhibitor-1
      and survival in patients with colorectal cancer.

PMID- 9549454
TI  - Management of deliberate self poisoning in adults in four teaching hospitals:
      descriptive study.

PMID- 9549455
TI  - Survival rates from interval cancer in NHS breast screening programme.

PMID- 9549458
TI  - ABC of allergies. Summer hay fever.

PMID- 9549457
TI  - Secondary prevention in acute myocardial infarction.

PMID- 9549456
TI  - Contribution of parental blood pressures to association between low birth weight
      and adult high blood pressure: cross sectional study.
AB  - OBJECTIVE: To examine the possibility that low birth weight is a feature of the
      inherited predisposition to high blood pressure. DESIGN: Cross sectional study.
      SETTING: Primary care medical centre in Edinburgh. SUBJECTS: One offspring of 452
      families (231 men and 221 women aged 16-26 years) in whom blood pressure, weight,
      and height were measured in 1986 and whose parents had blood pressure measured in
      1979. Birth weights were obtained from case records (270 offspring) or by
      questionnaires sent to the mothers (182 offspring). MAIN OUTCOME MEASURES: Birth
      weight and adult systolic blood pressure in offspring in relation to parental
      blood pressure. RESULTS: If parental blood pressures were not considered, a 1 kg
      decrease in birth weight was associated with a 2.24 mm Hg increase in systolic
      blood pressure of offspring (P = 0.06) after correction for current weight and
      sex. However, parental blood pressures correlated positively with blood pressure
      of offspring, and higher maternal blood pressure was associated with lower birth
      weight (-3.03 g/mm Hg, P < 0.01). After correction for parental blood pressures,
      a 1 kg decrease in birth weight was associated with only a 1.71 mm Hg increase in
      the systolic blood pressure of the offspring (P = 0.15). CONCLUSIONS: Low birth
      weight is a feature of the inherited predisposition to hypertension, perhaps
      because it is associated with higher maternal blood pressure during pregnancy.
      Parental blood pressure may be an important confounding factor in the relation
      between low birth weight and subsequent hypertension.

PMID- 9549459
TI  - Risk of diabetic nephropathy in potential living related kidney donors.

PMID- 9549460
TI  - Management of metastatic melanoma during pregnancy.

PMID- 9549461
TI  - Commentary: pregnancy should not have affected treatment for melanoma.

PMID- 9549462
TI  - Commentary: self interest is not the sole legitimate basis for making decisions.

PMID- 9549463
TI  - Genetic testing and public policy.

PMID- 9549464
TI  - Bereavement in adult life.

PMID- 9549465
TI  - Effectiveness and cost effectiveness of compression bandages should be shown.

PMID- 9549466
TI  - Claim for major advance in treatment of perforated peptic ulcer seems premature.

PMID- 9549467
TI  - Debate over screening for gestational diabetes. Screening should take place only
      in context of good quality controlled trials.

PMID- 9549468
TI  - Debate over screening for gestational diabetes. Scientific uncertainty is
      mirrored in clinical practice in Italy.

PMID- 9549469
TI  - Debate over screening for gestational diabetes. Evidence from randomised
      controlled trial is needed.

PMID- 9549470
TI  - Health status instruments should satisfy full range of methodological criteria.

PMID- 9549471
TI  - Effect on mortality of switching from cigarettes to pipes or cigars. Study
      underestimated difference in risk.

PMID- 9549472
TI  - Effect on mortality of switching from cigarettes to pipes or cigars. Patterns of
      inhalation are important.

PMID- 9549473
TI  - Effect on mortality of switching from cigarettes to pipes or cigars. "Switchers"
      will have had higher cumulative exposure to tobacco.

PMID- 9549474
TI  - Effect on mortality of switching from cigarettes to pipes or cigars. American
      study supported conclusions.

PMID- 9549475
TI  - Fact that no SHO post was given five years approval is worrying.

PMID- 9549476
TI  - BUPA and the tobacco industry. Chairperson of BUPA in Republic of Ireland is also
      chairperson of tobacco producer.

PMID- 9549477
TI  - Community based programmes can help to manage tuberculosis more effectively.

PMID- 9549478
TI  - Cognitive dysfunction after concussion. Authors did not to comment on the single
      truly significant result.

PMID- 9549479
TI  - Determining prognosis after acute myocardial infarction in the thrombolytic era.
      Rescue angioplasty after failed thrombolysis may put patients at risk.

PMID- 9549480
TI  - Number of unexplained symptoms and diseases is decreasing.

PMID- 9549481
TI  - The caring doctor is an oxymoron. General practice will develop best if "caring"
      is replaced by professionalism.

PMID- 9549482
TI  - The caring doctor is an oxymoron. Frequent callers to cooperatives provoke same
      feelings there.

PMID- 9549483
TI  - The caring doctor is an oxymoron. Out of hours emergencies and continuing
      problems need different approaches.

PMID- 9549484
TI  - The caring doctor is an oxymoron. GPs could refer patients to clinical
      hypnotherapists.

PMID- 9549485
TI  - The role of magnetic resonance techniques in understanding and managing multiple
      sclerosis.
AB  - Magnetic resonance (MR) techniques have had a major impact in the last 10-15
      years in understanding and managing multiple sclerosis. This review summarizes
      the current uses of MR in multiple sclerosis, based on the proceedings of a
      recent international workshop, under four headings: (i) technical issues; (ii)
      role in diagnosis; (iii) natural history studies in understanding the disease;
      (iv) application in clinical trials. The theory and methodology of relevant
      technical issues is outlined, in order to provide a framework with which to
      understand the potential and limitations of MR in addressing biological and
      clinical questions in multiple sclerosis. The principles underlying signal-to
      noise and contrast-to-noise ratio are discussed, along with the techniques and
      clinical results for conventional and fast spin echo T2-weighted imaging, fluid
      attenuated inversion recovery, detection of blood-brain barrier break down and
      hypointense lesions on T1-weighted images, magnetization transfer, T2 decay-curve
      analysis, MR spectroscopy, spinal cord imaging, diffusion imaging, and
      quantification of lesion load and atrophy. MRI has an extremely valuable role in
      confirming the clinical diagnosis of multiple sclerosis. T2-weighted brain
      imaging remains the standard diagnostic tool, but in some instances it is
      usefully complemented with gadolinium enhancement and spinal imaging. The caveat
      that the diagnosis of multiple sclerosis remains primarily a clinical one cannot
      be over-emphasized. Serial MRI studies have added much to our understanding of
      the natural history and pathophysiology of the disease. Blood-brain barrier
      breakdown is a consistent early feature of new lesion development in relapsing
      remitting and secondary progressive multiple, sclerosis, and this usually
      correlates with active inflammation and myelin breakdown. A number of the acute
      MR changes are reversible, but chronic persistent abnormalities in a number of MR
      parameters, such as reduced N-acetyl aspartate, low magnetization transfer
      ratios, atrophy and T1-hypointensity, suggest the presence of demyelination
      and/or axonal degeneration in many chronic lesions. The presence and extent of T2
      weighted MRI abnormalities at first presentation with a clinically isolated
      syndrome suggestive of demyelination strongly predicts the risk of developing
      clinically definite multiple sclerosis in the next few years. In established
      multiple sclerosis, however, the correlations between T2 abnormalities and
      disability are modest. This poor relationship partly relates to the discrepancy
      between lesion site and function in attempting to correlate locomotor disability
      with brain MRI findings. However, the correlations between brain lesion load and
      cognitive dysfunction in multiple sclerosis, whilst more evident, are still
      modest. A more important limitation is the low pathological specificity of
      abnormalities seen on T2-weighted images. Stronger correlations have been found
      between disability and new putative MR markers for demyelination and/or axonal
      degeneration. Serial studies using multiple MR techniques are now needed to
      further clarify pathophysiological mechanisms in multiple sclerosis. Serial MR
      has become an important tool in monitoring treatment efficacy. It provides data
      which can be readily analysed in a blinded fashion and which directly inspects
      the pathological evolution; it also enables a rapid and sensitive measure of
      treatment outcome in early relapsing-remitting and secondary progressive disease.
      Because of the modest clinical correlations it is, however, still appropriate
      that the definitive determinant of treatment efficacy remains a clinical one.
      Further work is needed to address issues of quality control in serial studies,
      statistical calculation of appropriate sample sizes, and optimization of the
      nature and frequency of MR outcomes measured.

PMID- 9549486
TI  - The Riddoch syndrome: insights into the neurobiology of conscious vision.
AB  - We have studied a patient, G.Y., who was rendered hemianopic following a lesion
      affecting the primary visual cortex (area VI), sustained 31 years ago, with the
      hope of characterizing his ability to discriminate visual stimuli presented in
      his blind field, both psychophysically and in terms of the brain activity
      revealed by imaging methods. Our results show that (i) there is a correlation
      between G.Y.'s capacity to discriminate stimuli presented in his blind field and
      his conscious awareness of the same stimuli and (ii) that G.Y.'s performance on
      some tasks is characterized by a marked variability, both in terms of his
      awareness for a given level of discrimination and in his discrimination for a
      given level of awareness. The observations on G.Y., and a comparison of his
      capacities with those of normal subjects, leads us to propose a simple model of
      the relationship between visual discrimination and awareness. This supposes that
      the two independent capacities are very tightly coupled in normal subjects
      (gnosopsia) and that the effect of a VI lesion is to uncouple them, but only
      slightly. This uncoupling leads to two symmetrical departures, on the one hand to
      gnosanopsia (awareness without discrimination) and on the other to agnosopsia
      (discrimination without awareness). Our functional MRI studies show that V5 is
      always active when moving stimuli, whether slow or fast, are presented to his
      blind field and that the activity in V5 co-varies with less intense activity in
      other cortical areas. The difference in cerebral activity between gnosopsia and
      agnosopsia is that, in the latter, the activity in V5 is less intense and lower
      statistical thresholds are required to demonstrate it. Direct comparison of the
      brain activity during individual 'aware' and 'unaware' trials, corrected for the
      confounding effects of motion, has also allowed us, for the first time, to
      titrate conscious awareness against brain activity and show that there is a
      straightforward relationship between awareness and activity, both in individual
      cortical areas, in this case area V5, and in the reticular activating system. The
      imaging evidence, together with the variability in his levels of awareness and
      discrimination, manifested in his capacity to discriminate consciously on some
      occasions and unconsciously on others, leads us to conclude that agnosopsia,
      gnosopsia and gnosanopsia are all manifestations of a single condition which we
      call the Riddoch syndrome, in deference to the British neurologist who, in 1917,
      first characterized the major aspect of this disability. We discuss the
      significance of these results in relation to historical views about the
      organization of the visual brain.

PMID- 9549487
TI  - A neuromodulatory role for the human amygdala in processing emotional facial
      expressions.
AB  - Localized amygdalar lesions in humans produce deficits in the recognition of
      fearful facial expressions. We used functional neuroimaging to test two
      hypotheses: (i) that the amygdala and some of its functionally connected
      structures mediate specific neural responses to fearful expressions; (ii) that
      the early visual processing of emotional faces can be influenced by amygdalar
      activity. Normal subjects were scanned using PET while they performed a gender
      discrimination task involving static grey-scale images of faces expressing
      varying degrees of fear or happiness. In support of the first hypothesis,
      enhanced activity in the left amygdala, left pulvinar, left anterior insula and
      bilateral anterior cingulate gyri was observed during the processing of fearful
      faces. Evidence consistent with the second hypothesis was obtained by a
      demonstration that amygdalar responses predict expression-specific neural
      activity in extrastriate cortex.

PMID- 9549488
TI  - A study of medial pallidotomy for Parkinson's disease: clinical outcome, MRI
      location and complications.
AB  - We have studied the effects of unilateral ventral medial pallidotomy in 26
      patients with medically intractable Parkinson's disease with marked drug-induced
      dyskinesias. Preoperatively, all patients were assessed during one 5-day
      admission according to the Core Assessment Programme for Intracerebral
      Transplantation (CAPIT) protocol, including rating in the 'practically defined
      off' and 'best on' states before and during a single-dose levodopa challenge.
      Motor performance was assessed with subset categories of the Unified Parkinson's
      Disease Rating Scale (UPDRS), timed motor tests and a standard dyskinesia rating
      scale. Pallidotomy was performed under stereotaxic CT guidance with intra
      operative extracellular microelectrode recording made from the basal ganglia. All
      patients were re-assessed 3 months postoperatively and a subgroup (n = 9) have so
      far also been re-assessed after 1 year. Pre- and postoperative performance scores
      were compared in order to determine which categories of performance improved
      postoperatively. Significance was accepted at P < 0.005 in order to take into
      account the multiple number of comparisons performed. Patient medication was
      compared pre- and postoperatively and the morbidity associated with surgery was
      also recorded. The most significant improvement postoperatively was the
      diminution of 'on' dyskinesias contralaterally (67%, P = 0.0001); however,
      ipsilateral (45%, P = 0.0006) and axial (50%, P = 0.0008) dyskinesias also
      improved. Contralateral to pallidotomy, the median 'off' motor UPDRS score
      improved by 27% (P = 0.001) and a significant improvement was also observed in
      contralateral rigidity by 25% (P = 0.001). There were trends towards improvement
      in contralateral tremor (33%, P = 0.016) and bradykinesia (24%, P = 0.013)
      scores. Ipsilateral rigidity improved by 22% (P = 0.005), but other ipsilateral
      motor scores did not alter significantly. The 'off' gait/postural instability
      score and 'off' walking time showed marginally significant improvements by 7% (P
      = 0.007) and 29% (P = 0.014), respectively. On medication, no significant
      postoperative improvements in parkinsonism were detected. Anti-parkinsonian
      medication increased by 11% postoperatively. In the subgroup who were available
      for assessment 1 year postoperatively, responses were generally maintained. Two
      (7.7%) of the 26 patients had fatal complications (one cerebral haemorrhage and
      one haemorrhagic infarct) directly related to surgery. Among the remaining 24
      patients, four (15.4% of the total 26) had major complications (two persisting
      and two transient). Ten patients (38.5%) had minor complications. The majority of
      the complications (major and minor) occurred in the earlier operated patients and
      the complication rate subsequently declined with increasing operative experience.
      The remaining 10 patients (38.5%) had no significant side-effects. One of these
      10 patients died from an incidental malignant glioma 6 months postoperatively.
      These findings confirm that levodopa-induced dyskinesias are dramatically reduced
      following ventral medial pallidotomy and constitute the principal indication for
      pallidotomy. Improvements in underlying parkinsonism were of smaller magnitude.
      Pallidotomy may also offer some patients an opportunity to increase
      antiparkinsonian medication. Patient selection for medial pallidotomy should,
      therefore, be based largely on anticipated improvements in levodopa-induced
      dyskinesias, but this must be balanced against the associated morbidity and
      mortality.

PMID- 9549489
TI  - Dynamic aphasia: an inability to select between competing verbal responses?
AB  - In this study we report a patient (A.N.G.) who, following a malignant left
      frontal meningioma impinging upon Brodmann area 45, presented a 'pure' dynamic
      aphasia. Her spontaneous speech was markedly reduced in the absence of any
      syntactical impairment. Her naming, repetition and reading skills were completely
      normal. Two experimental investigations were carried out. The first investigation
      found that A.N.G. had a profound impairment in phrase and sentence generation
      tasks given a verbal context. However, her verbal generative skills were normal
      when she was asked to describe pictorial scenes and complex actions. Moreover, it
      was found that A.N.G. had no difficulty ordering the constituent words of a
      sentence. Thus, it was concluded that her verbal planning skills were intact. The
      second investigation tested a hypothesis that dynamic aphasia is due to an
      inability to select a verbal response option whenever the stimulus activates many
      competing verbal responses. Predictions based upon this hypothesis were confirmed
      on three different verbal generation tasks. It was found that our patient's grave
      verbal generative impairment was present for tasks involving stimuli which
      activate many potential responses. However, it was absent for tasks involving
      stimuli which activate few or only a single 'prepotent' response. The findings
      are discussed with reference to traditional interpretations of dynamic aphasia
      and more general interpretations of prefrontal cortex functioning. On the basis
      of a computational model of prefrontal cortex functioning, we propose that pure
      dynamic aphasia may be caused by damage to a 'context' module containing units
      responsible for selection of verbal response options. Moreover, it is suggested
      that our findings support the view that Brodmann area 45 is involved in verbal
      response generation to stimuli which activate many potential response options.

PMID- 9549490
TI  - What is straight ahead to a patient with torticollis?
AB  - Vestibular and neck proprioceptive signals are known to be used in judging the
      locations of objects in space and relative to the body. Given that these signals
      are asymmetric in patients with spasmodic torticollis, one would expect such
      patients to have abnormal spatial perception. We tested this idea by measuring
      patients' perception of visual straight ahead (VSA) under various conditions:
      with the body in its primary position, i.e. with the head and trunk as closely
      aligned as possible, and after well defined passive rotations of the head and/or
      trunk. In the primary body position, patients' VSA direction showed considerable
      variations which were similar, however, to those of normal subjects; it was
      independent of torticollis direction, of the head torque it produced, and of the
      weak spontaneous nystagmus recorded in seven of the 10 patients. After whole-body
      rotations, i.e. where head and trunk underwent the same motion, the VSA was
      shifted in both patients and normal subjects, and in both groups the shift was
      symmetrical after rotations to the right or left. After motions where the trunk
      rotated under the stationary head (neck proprioceptive stimulation) or the head
      on the stationary trunk (combined vestibular and neck stimulus), the VSAs of
      normal subjects coincided rather well with their head midsagittal planes, whereas
      the VSAs of patients were shifted considerably towards the trunk, again in a
      symmetrical way. We suggest two mechanisms to explain the findings in patients:
      (i) a central compensation which restores symmetry of the afferent inflow in the
      patients (unlike the motor efference); (ii) shifting of the reference for the VSA
      from the head towards the trunk, because the trunk is a more reliable egocentric
      reference than the head in the patients. Our findings do not support the
      assumption that asymmetries in afferent inflow are responsible for the asymmetry
      of motor output in spasmodic torticollis.

PMID- 9549491
TI  - Imaging axonal damage of normal-appearing white matter in multiple sclerosis.
AB  - The current study was designed to determine the relative distribution of
      decreases of N-acetylasparate (NAA), a marker of axonal damage, between lesions
      and normal-appearing white matter of patients with established multiple sclerosis
      and to test for associations between changes in the ratio of NAA to
      creatine/phosphocreatine (NAA:Cr) in those compartments and changes in
      disability. Data were collected from a 30-month longitudinal study of 28 patients
      with either a relapsing course with partial remissons and no progression between
      attacks (relapsing/remitting) (11 patients) or a course of progressively
      increasing disability, following a period of relapsing/remitting disease
      (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic
      imaging (MRSI) and conventional MRI examinations were performed at 6-8-month
      intervals with concurrent clinical assessments of disability. General linear
      models were used to test associations between MRSI, MRI, lesion volume and
      clinical data. Analysis confirmed that the NAA:Cr ratio is lower in lesions than
      in the normal-appearing white matter (-15.3% in relapsing/remitting multiple
      sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower
      NAA:Cr ratio per unit lesion volume previously observed for secondary progressive
      relative to relapsing/remitting patients was found to result from a lower ratio
      (8.2%, P < 0.01) in the normal-appearing white matter rather than from any
      differences within lesions. The importance of changes in the normal-appearing
      white matter was emphasized further with the observation that the NAA:Cr ratio in
      the normal-appearing white matter accounted for most of the observed 15.6% (P <
      0.001) decrease in the NAA:Cr ratio in the brains of relapsing/remitting patients
      over the period of study. The decrease in the NAA:Cr ratio in normal-appearing
      white matter correlated strongly (P < 0.001) with changes in disability in the
      relapsing/remitting subgroup. These results add to data suggesting that axonal
      damage or loss may be responsible for functional impairments in multiple
      sclerosis. The accumulation of secondary axonal damage in the normal-appearing
      white matter may be of particular significance for understanding chronic
      disability in this disease.

PMID- 9549492
TI  - A case of primary progressive aphasia. A 14-year follow-up study with
      neuropathological findings.
AB  - Primary progressive aphasia has been clinically defined as a progressive language
      deficit leading to the dissolution of almost all language functions with relative
      preservation of other cognitive functions until late in the course of the
      disease. Two types of language impairment have been described for primary
      progressive aphasia, which differ with respect to the degree of fluency of
      spontaneous speech. Whereas some authors have emphasized non-fluency as a
      defining characteristic of primary progressive aphasia, others have proposed that
      phonemic rather than semantic paraphasias in naming, both in the fluent and the
      non-fluent subtype, should be used as a criterion to distinguish primary
      progressive aphasia from slowly progressive aphasia in other forms of
      degenerative brain disease. Patients with fluent speech and semantic dementia, as
      typically seen in Alzheimer's disease, produce semantic paraphasias and
      circumlocutions rather than phonemic errors in naming. This paper reports the
      long-term follow-up of a patient with fluent aphasic speech, whose language
      profile over a decade was similar to that of patients with semantic dementia.
      Neuropathological examination revealed no evidence of Alzheimer's disease. Pick's
      disease or Pick variant, but showed spongiform changes of cortical layers (II and
      III) in temporal and, less severely, in frontal gyri. The present case indicates
      that semantic dementia is not a reliable indicator of probable Alzheimer's
      disease and supports the notion that there are different subtypes of primary
      progressive aphasia which cannot be defined by fluency or by the presence of
      phonemic paraphasia. Progress in identifying the neuropathological correlates of
      these subtypes in cases with lobar atrophy and spongiform changes should be
      expected from hereditary variants of progressive disorder.

PMID- 9549493
TI  - Endozepine stupor. Recurring stupor linked to endozepine-4 accumulation.
AB  - Recurring stupor can be caused by repeated metabolic, toxic or structural brain
      disturbances. Recently, cases of recurring stupor, with fast EEG activity were
      shown to display increased endogenous benzodiazepine-like activity during the
      episodes of stupor. Patients with recurring stupor underwent extensive metabolic
      and toxicologic screening, EEG and brain imaging. Endozepines and exogenously
      administered benzodiazepines were assayed in plasma and CSF by means of mass
      spectrometry. Flumazenil, a benzodiazepine antagonist was administered and the
      behavioural and EEG responses monitored. Treatment with oral flumazenil was
      attempted in selected cases. Twenty patients were found with recurring stupor.
      Episodes had begun between ages 18 and 67 years, and in nine patients, had
      disappeared spontaneously after 4-6 years with symptoms. Stupor lasted hours or
      days. Onset of the episodes and frequency were unpredictable. Patients were
      normal between attacks. Stupor was characterized by initial drowsiness,
      staggering and behavioural changes, followed by deep sleep and spontaneous
      recovery with post-ictal amnesia. Biochemical screening and brain imaging were
      always normal. Ictal EEG showed fast background activity, and flumazenil
      transiently awoke the patients and normalized the EEG. In the nine cases
      examined, endozepine-4 levels were increased during the stupor. Oral flumazenil
      reduced the frequency of the attacks in three of these nine patients. Recurring
      episodes of stupor may be due to increased endozepine-4. We propose the term
      'endozepine stupor' for such episodes. Endozepine-4 is an endogenous ligand for
      the benzodiazepine recognition site at the GABAA receptor, with unknown molecular
      structure.

PMID- 9549494
TI  - Cognitive process in preclinical phase of dementia.
AB  - Several recent prospective studies have demonstrated the existence of a
      preclinical stage of dementia, identifiable by neuropsychological assessment
      showing impairments with a great variety of cognitive tests. However, test scores
      are often colinear, largely because common cognitive components are involved in
      different tests; in spite of an apparent heterogeneity, it is still possible that
      a common cognitive component may be responsible for the deterioration shown in
      different tests in the preclinical phase. We studied the cognitive performances
      of 1159 elderly residents in the PAQUID (Personnes Agees quid) cohort, at a fixed
      lag time of 2 years before the clinical diagnosis of dementia. Seven
      neuropsychological tests were administered (Mini-Mental Status Examination,
      Benton Visual Retention Test, Wechsler Paired-Associates Test, Isaacs Set Test,
      Zazzo's Cancellation Task, Digit Symbol Substitution Test and Wechsler
      Similarities Test). Among the initially non-demented 1159 subjects, 25 developed
      a dementia 2 years later, of whom 16 were classified as cases of Alzheimer's
      disease. In order to dissect the multicolinearity of the tests we used a
      multivariate approach with principal component analysis (PCA). The patients'
      loading on each of the first four PCA factors were subsequently correlated with
      the risk of dementia and Alzheimer's disease 2 years later. The logistic
      regression with backward stepwise selected only the first factor as an
      independent predictor of dementia or Alzheimer's disease. Analysis shows that
      there are good reasons to suspect that the first PCA factor represents a general
      factor corresponding to aspects of control in the tasks used. Our results
      therefore seem to show that preclinical deficits in dementia and Alzheimer's
      disease reflect the deterioration of a general cognitive factor, which may be
      interpreted as the disturbance of central, control processes.

PMID- 9549495
TI  - Human cerebral activity evoked by motion reversal and motion onset. A PET study.
AB  - In this PET study, we have investigated the human brain activity evoked by a
      visual motion paradigm commonly used to measure motion-related visual evoked
      potentials (VEPs). Because standard PET activation studies have been performed
      with motion along four axes, we first determined the pattern of brain activation
      when motion was restricted to a single axis. Motion back and forward along a
      single horizontal axis compared with a static condition revealed weak
      differential activations in the cuneus and the parietal cortex. Human area MT/V5
      (middle temporal area) was hardly activated at all in this subtraction.
      Additional functional MRI experiments proved that MT/V5 activity is significantly
      higher for motion along four axes than for motion along a single axis. Secondly,
      we attempted to isolate the pattern of brain activity related to the reversal of
      motion direction and to the onset of motion, i.e. two transient motion components
      commonly used in measuring motion-related VEPs. To that end, we added a
      continuous linear contrast modulation, that reached maximum contrast at reversal
      or onset of motion, and compared both conditions with a contrast-modulated static
      or continuous motion condition. Subtraction of the static random dot pattern
      condition from the single-axis motion reversal condition, both contrast
      modulated, revealed three significant activations: the anterior parieto-occipital
      sulcus, the lateral sulcus and the anterior claustrum. Additional analysis showed
      that these activations were not due to motion appearance or disappearance, but
      were due to the combination of motion reversal and contrast modulation. Hence,
      these activations do not reflect the motion reversal transient per se. In order
      to isolate a metabolic response to the reversal transient per se, we used a
      conjunction analysis, which suggests that activity in human MT/V5, the cuneus and
      a parietal insular region could underlie the motion reversal VEP in our
      experiments. Subtraction of the static random dot pattern condition from the
      single-axis motion onset condition, both contrast-modulated, revealed a single
      significant activation in the posterior cingulate cortex. Although the
      significance of this activation is unclear, it adds further evidence for the
      visual function of this region.

PMID- 9549496
TI  - Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune
      encephalomyelitis.
AB  - Matrix metalloproteinases (MMPs) comprise a group of proteolytic enzymes that are
      implicated in the pathogenesis of inflammatory diseases of the nervous system
      such as multiple sclerosis. However, the exact function and expression pattern of
      MMPs in the inflamed nervous system are not known. In the present study we
      investigated the expression of 92-kDa gelatinase (MMP-9) in spinal cord from
      animals with adoptive transfer experimental autoimmune encephalomyelitis (AT
      EAE), using a semiquantitative competitive reverse transcriptase-polymerase chain
      reaction assay. Increased levels of MMP-9 mRNA were found with peak values at
      times of maximum disease severity. Increased mRNA expression was associated with
      enhanced proteolytic activity of this enzyme, as demonstrated by gelatin
      zymography. Immunohistochemistry revealed immunoreactivity along the meninges,
      around blood vessels and within the parenchyma, in diseased but not in normal
      spinal cord. Furthermore, the expression pattern of five other MMPs was
      investigated. Matrilysin (MMP-7) was also found to be upregulated with maximum
      mRNA levels at the peak of the disease. In contrast, mRNAs for collagenase-3, 72
      kDa gelatinase, and stromelysin-1 and -3 were not changed. Our findings indicate
      that 92-kDa gelatinase and matrilysin are selectively upregulated during AT-EAE
      and thus may contribute to the pathogenesis of inflammatory diseases of the CNS.

PMID- 9549497
TI  - Reliance on external cues for movement initiation in Parkinson's disease.
      Evidence from movement-related potentials.
AB  - The aim of this study was to investigate the neurophysiological mechanisms
      underlying Parkinson's disease patients' increased reliance on external cues for
      the initiation of movement. Lateralized movement-related cortical potentials were
      recorded in a noise-compatibility task with seven patients and seven age-matched
      control subjects. In this two-choice task, visual stimuli containing incompatible
      target and distractor elements, which simultaneously instructed for responses
      from both hands, initially caused activation of the motor cortex controlling the
      wrong response hand. The incorrect response activation was of higher amplitude in
      patients than in control subjects, causing a longer response delay relative to
      response times when target and distractors instructed the same hand. In addition,
      hand-specific motor cortex activation started earlier in patients than in control
      subjects. These results indicate that visual stimuli exerted an earlier and
      stronger influence on movement initiation in patients than in control subjects.
      We hypothesize that information from sensory stimuli relevant for the generation
      of a response can have rapid access to motor structures in Parkinson's disease
      patients, thereby facilitating the initiation of movement. The findings may
      reflect a compensatory mechanism, but could also be related to excitability
      changes in the motor cortex intrinsic to the pathophysiology of Parkinson's
      disease.

PMID- 9549498
TI  - Cochlear sound-movement and musical misperception.

PMID- 9549499
TI  - Neurological abnormalities in familial and sporadic schizophrenia.
AB  - Neurological assessment was carried out on patients with schizophrenia from
      multiply and singly affected families, their relatives, and a normal control
      group (214 subjects). A systematic examination was used in which abnormal signs
      were divided into 'primary' and 'integrative' signs. Primary signs were elicited
      by a standard clinical neurological examination and included signs of focal
      damage to nuclei and tracts, whilst integrative signs were selected as reflecting
      distributed brain function. The assessments were carried out to test the
      hypotheses that (i) neurological abnormalities are present in schizophrenia, (ii)
      the pattern of abnormality is different in familial and sporadic schizophrenic
      subjects, and (iii) the well relatives of familial (but not sporadic)
      schizophrenic subjects will show neurological abnormalities. An excess of primary
      signs compared with the controls was demonstrated in the sporadic schizophrenic
      group only. Both the familial schizophrenics and their first-degree relatives
      (but not their sporadic counterparts) showed an increase in integrative signs.
      The results support the existence of different mechanisms of underlying brain
      dysfunction in familial and sporadic schizophrenia.

PMID- 9549500
TI  - Autosomal dominant nocturnal frontal lobe epilepsy. A video-polysomnographic and
      genetic appraisal of 40 patients and delineation of the epileptic syndrome.
AB  - A number of clinical and aetiological studies have been performed, during the
      last 30 years, on patients with abnormal nocturnal motor and behavioural
      phenomena. The aetiological conclusions of these studies were often conflicting,
      suggesting either an epileptic or a non-epileptic origin. Among the clinical
      characteristics of these patients, the familial clustering was one thoroughly
      accepted. A nocturnal familial form of frontal lobe epilepsy (autosomal dominant
      nocturnal frontal lobe epilepsy, ADNFLE), often misdiagnosed as parasomnia, has
      been recently described in some families. In one large Australian kindred, a
      missense mutation in the second transmembrane domain of the neuronal nicotinic
      acetylcholine receptor alpha 4 subunit (CHRNA4) gene, located on chromosome 20
      q13.2-13.3, has been reported to be associated with nocturnal frontal lobe
      epilepsy. We performed an extensive clinical and video-polysomnographic study in
      40 patients complaining of repeated abnormal nocturnal motor and/or behavioural
      phenomena, from 30 unrelated Italian families. Thirty-eight patients had an
      electroclinical picture strongly suggesting the diagnosis of ADNFLE. They had a
      wide clinical spectrum, ranging from nocturnal enuresis to sleep-related violent
      behaviour, thus including all the main features of the so-called 'typical'
      parasomnias. The video-polysomnographic recording confirmed the wide spectrum of
      abnormal manifestations, including sudden awakenings with dystonic/ dyskinetic
      movements (in 42.1% of patients), complex behaviours (13.2%) and sleep-related
      violent behaviour (5.3%). The EEG findings showed ictal epileptiform
      abnormalities predominantly over frontal areas in 31.6% of patients. In another
      47.4% of patients the EEG showed ictal rhythmic slow activity over anterior
      areas. Only 18.4% of the patients had already received a correct diagnosis of
      epilepsy. In 73.3% of the patients treated with anti-epileptic drugs the seizures
      were readily controlled. Pedigree analysis on 28 of the families was consistent
      with autosomal dominant transmission with reduced penetrance (81%). DNAs from 20
      representative affected individuals were sequenced in order to check for the
      presence of the missense mutation in the CHRNA4 gene found in the Australian
      kindred affected by ADNFLE. Nucleotide sequence analysis did not reveal the
      presence of this mutation, but it did confirm the presence of two other base
      substitutions, not leading to amino acid changes. These two intragenic
      polymorphisms, together with a closely linked restriction fragment length
      polymorphism at the D20S20 locus, have been used for linkage analysis of ADNFLE
      to the terminal region of the long arm of chromosome 20 in five compliant
      families. The results allowed us to exclude linkage of ADNFLE to this chromosomal
      region in these families, thus confirming the locus heterogeneity of the
      disorder. Large and full video-polysomnographical studies are of the utmost
      importance in order to clarify the real prevalence of both nocturnal frontal lobe
      epilepsy and parasomnias, and to provide a correct therapy.

PMID- 9549501
TI  - Secondary progressive multiple sclerosis: the relationship between short-term MRI
      activity and clinical features.
AB  - We report the findings in 60 patients with secondary progressive multiple
      sclerosis who had monthly brain MRI studies for 4 months (one baseline and three
      follow-up scans). The purpose was to define the short-term MRI natural history in
      a large cohort with secondary progressive disease and to ascertain its
      relationship with other clinical and MRI features. The patients were
      participating in either a natural history study or the placebo arm or non
      treatment phase of a therapeutic trial. The cohort had clinical features typical
      of secondary progressive disease: thus, all had moderate or severe locomotor
      disabilities [Expanded Disability Status Scale (EDSS), score 3.5-8], with a
      median disease duration of 12 years. There was equal representation of males and
      females. During the 3 months of follow-up there was a total of 362 new enhancing
      lesions seen in 42 patients, and there were 24 relapses in 20 patients. There was
      no correlation between new enhancing lesions and age at study entry, age of
      disease onset, gender disease duration or EDSS, but there was a strong
      correlation with the number of enhancing lesions on the baseline scan (r = 0.65,
      P < 0.0001) and subsequent activity. There was a non-significant trend for higher
      numbers of new enhancing lesions in those having relapses during the 3 months of
      scanning (P = 0.14) or in the preceding 6 months (P = 0.06). The 34 patients who
      did not relapse in either period had significantly fewer new active lesions (P =
      0.02) than those who relapsed at some stage during the 9 months. Nevertheless,
      considerable activity was seen in the non-relapsing cohorts: there was a mean of
      3.5 (median 2) new enhancing lesions in those not relapsing during the 3 month
      study, and 5.5 (median 2) in those not relapsing in the previous 6 months. We
      conclude that short-term MRI activity is generally high in secondary progressive
      disease, confirming a useful role for the technique in exploratory trials.
      Further work should concentrate on elucidating the mechanisms of secondary
      progression by longer term follow-up studies of larger cohorts using multiple MRI
      and clinical measurements.

PMID- 9549502
TI  - Visual evoked potentials during long periods of pattern-reversal stimulation in
      migraine.
AB  - We have previously shown that during repetitive pattern-reversal stimulation,
      lasting 2 min, the amplitude of the visual evoked potential (PR-VEP) increases in
      migraineurs when tested interictally whereas it decreases in healthy control
      subjects. According to Sappey-Marinier et al. (J Cereb Blood Flow Metab 1992; 12:
      584-92) habituation of the PR-VEP in normal subjects is maxima after 12 min, at a
      time when there is a decrease of stimulation-enhanced lactate levels in the
      occipital cortex. We have therefore compared PR-VEP during long periods of
      repetitive stimulation in healthy control subjects (n = 25) and in patients
      suffering from migraine without (n = 25) and with aura (n = 15) between attacks.
      During uninterrupted stimulation at 3.1 Hz VEPs were sequentially averaged in
      blocks of 100 responses for a total duration of 15 min and analysed in terms of
      latencies and peak-to-peak amplitudes of N1-P1 and P1-N2 peaks. Amplitude changes
      from the baseline were calculated for each block, by comparison with the first
      block, and analysed statistically using Zerbe's method. The N1-P1 and P1-N2
      amplitudes in the first block tended to be lower in migraineurs than in healthy
      control subjects. During the 15 min of stimulation, amplitudes of both components
      progressively decreased in control subjects, but remained stable in both groups
      of patients. The difference between patients and control subjects proved to be
      significant (P < 0.05). The neurophysiological data were not correlated with
      clinical features such as attack frequency or duration of illness. These results
      are yet another demonstration in migraine of an interictal habituation deficit in
      cortical information processing, which might favour lactate accumulation in
      sensory cortices during sustained activation.

PMID- 9549503
TI  - Status dystonicus: the syndrome and its management.
AB  - Patients with dystonic syndromes sometimes develop increasingly frequent and
      relentless episodes of devastating generalized dystonia which we call status
      dystonicus. Twelve cases of status dystonicus, of various underlying aetiologies,
      are presented. Possible precipitating factors were identified in only five cases:
      intercurrent infection (one); discontinuation of lithium (one) and tetrabenazine
      (one); and the introduction of clonazepam (two). Nine patients required
      mechanical ventilation and three others were sedated with intravenous
      chlormethiazole. Drug therapy used included benzhexol, tetrabenazine, pimozide,
      baclofen, chlorpromazine, haloperidol, carbamazepine and acetozolamide. Two
      patients underwent thalamotomies, one of whom improved. Two patients died, five
      returned to their pre-status dystonicus condition, two eventually made a full
      recovery and three were worse. Patients with status dystonicus should be managed
      on an intensive care unit as they may develop bulbar and respiratory
      complications which may require ventilation. Metabolic problems encountered can
      include rhabdomyolysis with acute renal failure. Drug therapy with benzhexol,
      tetrabenazine and pimozide or haloperidol may be beneficial in some cases.

PMID- 9549504
TI  - The functional neuroanatomy of simple and complex sequential finger movements: a
      PET study.
AB  - The brain regions activated by simple repetitive and sequential finger movements
      of different length were localized by measuring regional cerebral blood flow
      (rCBF) with PET. The experimental design consisted of finger movements cued by
      auditory pacing at 0.5 Hz. In all conditions of different sequence length the
      contralateral primary sensorimotor and premotor cortex, supplementary motor area
      and ipsilateral cerebellar cortex were activated. These areas showed a large
      increase in activation from rest to simple repetitive movement, and a further
      increase with the shortest sequence, suggesting an executive role in running
      sequences. The ipsilateral premotor area (Brodmann area 6), bilateral posterior
      parietal areas (Brodmann area 7) and precuneus showed an increase in rCBF related
      only to the length of the sequences, without any change from rest to simple
      repetitive movement. These areas are more selectively related to sequence
      performance. This finding is consistent with the hypothesis that these areas
      function in the storage of motor sequences in spatial working memory. Our results
      suggest that sequential finger movements recruit discrete sets of brain areas
      with different functions.

PMID- 9549505
TI  - Clustering of slowly adapting type II mechanoreceptors in human peripheral nerve
      and skin.
AB  - The intrafascicular organization of human peripheral nerves was studied with
      percutaneous microneurography in the median, radial and peroneal nerves with one
      surface or two-surface thin diameter concentric needle electrodes. Data from 33
      recording sites containing 47 slowly adapting type II (SAII) units were analysed.
      At many sites two, sometimes even three, neighbouring SAII units were recorded
      from the explored nerve fascicle and they had adjacent or even overlapping
      cutaneous receptive fields. Among pairs of SAII units found at the same site, one
      unit often had ongoing discharge, whereas the other was silent under resting
      conditions. The neighbouring SAII units were optimally activated by stretching
      the skin in different directions. Stretching the same skin area in different
      directions produced different unit recruitment. Clustered SAII units were often
      found in sites where Pacinian afferents and skin sympathetic activity were also
      recorded. No significant difference was observed in the degree of grouping of
      SAII units either between recordings obtained with one-surface versus two-surface
      electrodes or between glabrous and hairy skin. The data do not support the notion
      that myelinated fibres are randomly organized in peripheral nerve fascicles.
      Instead, the findings suggest that SAII units tend to be clustered in human
      peripheral nerves. Furthermore, the response of groups of SAII units to skin
      stretch suggests that they play a role in proprioception. Dual channel recordings
      with two-surface concentric needle electrodes may provide a novel approach to
      study fibre organization in human peripheral nerves and the behaviour of groups
      of nerve fibres.

PMID- 9549506
TI  - Somatosensory-evoked blink response: investigation of the physiological
      mechanisms.
AB  - The somatosensory-evoked blink response (SBR) is a newly identified blink reflex
      elicited by electrical stimulation of peripheral nerves. The present study was
      performed to investigate the physiological mechanism underlying the SBR elicited
      by median nerve stimulation in normal subjects. The peripheral afferents
      responsible for the SBR included low-threshold cutaneous fibres. In the SBR
      positive subjects, the late (R2) component of the blink reflex elicited by
      supraorbital nerve stimulation and the SBR facilitated each other when both
      responses were induced at the same time, but they each caused long-lasting
      inhibition in the other when one stimulus was given as a conditioning stimulus.
      The extent of inhibition was correlated with the size of the preceding SBR. In
      the SBR-negative subjects, simultaneous inhibition of R2 was observed when median
      nerve stimulation was applied as a conditioning stimulus. Brainstem excitability,
      as evaluated by blink-reflex recovery studies, did not differ between SBR
      positive and SBR-negative subjects. Therefore, based on anatomical and
      physiological findings, it appears that the reflex pathways of the SBR and R2
      converge within the brainstem and compete with each other, presumably by
      presynaptic inhibition at the premotor level, before entering the common blink
      reflex pathway. The influence of median nerve stimulation upon tonic contraction
      of the orbicularis oculi muscle was studied to detect the latent SBR. There was
      not only a facilitatory period corresponding to the SBR but also an active
      inhibitory period (exteroceptive suppression), suggesting that the mechanism
      generating the SBR is not only influenced by blink-reflex volleys but also by
      active exteroceptive suppression. Thus, the SBR may appear as a result of
      integration of facilitatory and inhibitory mechanisms within the brainstem.

PMID- 9549507
TI  - Identification of the adult resting progenitor cell by autoradiographic tracking
      of oligodendrocyte precursors in experimental CNS demyelination.
AB  - The new population of oligodendrocytes remyelinating an experimental
      demyelinating optic nerve lesion has been tracked backwards in time. Using
      autoradiography combined with electron microscopy and immunocytochemistry, serial
      sections of optic nerves from young adult cats were studied from 42 h (2 days)
      post-injection to 93 h (4 days) post-injection. The remyelinating oligodendrocyte
      lineage was found to commence with the single division of a resting progenitor
      cell residing in a central fascicular location outside the demyelinative lesion.
      The division of the founding progenitor cell occurs at 2 days post-lesion and
      results in two motile daughter cells. These cells, previously described by us as
      precursor cells, migrate to the lesion, closely appose demyelinated axons,
      produce axon wrapping processes and differentiate to become remyelinating
      oligodendrocytes. This study confirms that remyelinating oligodendrocytes
      originate from resting progenitor cells outside the lesion and not from mature
      oligodendrocytes, and implies that repeated demyelinative injury could exhaust
      the reparative capacity of such a region.

PMID- 9549508
TI  - Clinical and genetic analysis of a large Dutch family with autosomal dominant
      vascular retinopathy, migraine and Raynaud's phenomenon.
AB  - We describe an extended Dutch family with a new hereditary disorder: autosomal
      dominant vascular retinopathy, migraine and Raynaud's phenomenon. Information was
      obtained on 289 family members (151 males, 138 females), of whom 198 were
      personally interviewed. Retinopathy was found in 20 (6.9%) of the family members,
      migraine in 65 (22.5%) and Raynaud's phenomenon in 50 (17.3%). A combination of
      all three symptoms was found in 11 subjects. In a genetic linkage analysis we
      firstly excluded several candidate loci. Subsequently, 75% of the autosomal
      genome was excluded in a genome-wide search. The following conclusions were
      drawn. First, genetic factors are involved in Raynaud's phenomenon. Secondly, the
      genetic linkage of migraine with vascular retinopathy and Raynaud's phenomenon
      supports a vascular aetiology of this disorder. Finding the gene for this family
      may help to elucidate the genetic background of migraine and of vascular
      disorders in general.

PMID- 9549509
TI  - The subjective handicap of epilepsy. A new approach to measuring treatment
      outcome.
AB  - It is now widely acknowledged that the impact of epilepsy on the individual
      extends beyond the occurrence of seizures, and that there is a need for outcome
      measures sensitive to these consequences. Until now these instruments have
      largely been developed within a 'quality of life' framework. The technical and
      conceptual difficulties that arise with measuring quality of life have led us to
      develop a more focused measurement model, the 'Subjective Handicap of Epilepsy'
      (SHE) scale, based on the World Health Organization's concept of handicap. The
      scale contains 32 items in six subscales: 'Work and activities' (eight items),
      'Social and personal' (four items), 'Self-perception' (five items), 'Physical'
      (four items), 'Life-satisfaction' (four items) and a 'Change' scale (seven
      items); and it takes on average < 10 min to complete. The scale's test-retest
      reliability was found to be satisfactory (intra-class correlation coefficient was
      0.8-0.9 in 110 subjects). The test-retest interval (24 h to 8 weeks) had no
      influence on the reliability. The reliability was also not affected by minor
      recent fluctuations in seizure frequency. The internal consistency of the scales
      was 0.8-0.9 (Cronbach's alpha). The construct validity of the scale was examined
      in a sample of 287 clinic attendees at a university neurology clinic in the UK.
      The scales were highly sensitive to the handicapping effects of increasing
      seizure frequency, employment status, the impact of epilepsy on career choice and
      the subject's own opinion as to the major determinant of their quality of life.
      The scales were also sensitive, retrospectively, to the benefits of successful
      epilepsy surgery in a cohort of 105 patients. Scales focusing specifically on
      handicap were more sensitive to group differences in seizure frequency in the
      clinic population, and to outcome after epilepsy surgery, than the 'Life
      satisfaction' scale and the Epilepsy Surgery Inventory 55 (ESI-55) scales. This
      supports the contention that measuring 'subjective handicap' may be a more
      sensitive, and more useful, approach to assessing the impact of interventions on
      the long-term consequences of epilepsy than current methods.

PMID- 9549510
TI  - Allodynia after lateral-medullary (Wallenberg) infarct. A PET study.
AB  - We used PET to study regional cerebral blood flow (rCBF) changes in nine patients
      with unilateral central pain after a lateral medullary infarct (Wallenberg's
      syndrome). All patients presented, on the abnormal side, a combination of
      hypaesthesia to noxious and thermal stimuli and allodynia to rubbing of the skin
      with a cold object (i.e. abnormal pain to innocuous stimulation). The rCBF
      responses during allodynia were compared with those obtained during stimulation
      of the normal side using (i) a cold non-noxious stimulus identical to that
      applied to the painful side, and (ii) an electrical high-frequency stimulus at
      painful ranges. Statistical analysis disclosed two abnormal patterns of rCBF
      change during allodynia. First, there is a quantitative change whereby the blood
      flow response was out of proportion with the actual intensity of the stimulus,
      i.e. the pattern of activation by innocuous rubbing of the skin was in our
      patients identical to that previously reported in response to painful stimuli in
      normal subjects. This pattern concerned primarily the contralateral thalamus in
      its lateral half and the primary and somatosensory areas, as well as inferior
      parietal [Brodmann area (BA) 39/40], anterior insular (BA 6) and medial
      prefrontal (BA 10) cortices. Thalamic over-activity may reflect abnormal
      transduction and amplification of sensory inputs after spinothalamic
      deafferentation. This might be responsible for both increased rCBF in multiple
      cortical targets and the perceived shift of stimulus intensity from innocuous to
      painful ranges. The second abnormality associated with allodynic sensation was
      qualitative. It concerned exclusively the contralateral cingulate gyrus, which
      did not exhibit the usual pain-related rCBF increase reported in normal subjects.
      This abnormal cingulate response may account for the peculiar response of lateral
      medullary infarct patients to allodynic pain, which is not simply perceived as an
      exaggerated pain sensation, but as a new, strange and extremely unpleasant
      feeling, not previously experienced by the patients.

PMID- 9549511
TI  - Influence of vision on upper limb reaching movements in patients with cerebellar
      ataxia.
AB  - The effects of vision on spatial and temporal characteristics of free
      unrestrained reaching movements of the arm were examined in 17 patients with
      ataxic syndromes due to degenerative disease of the cerebellum and its
      connections. Subjects were required to reach out and touch a visually presented
      target either in the dark or with the target and their finger visible. Overall,
      patients had prolonged reaction times and their movements were performed slower
      than normal. The spatial paths described by their fingertips were more
      circuitous, being of greater length than normal, a characteristic that was
      uninfluenced by visual conditions. Ataxic movements were less accurate than
      normal in two ways. First, there was greater spatial variability between repeat
      paths to the same target. The increased variability was present very early in the
      movement trajectory and at that stage was not influenced by visual feedback.
      Secondly, there were large constant errors at the end of movement, but only when
      moving in darkness. Patients with Friedreich's ataxia as well as those with
      intrinsic cerebellar degeneration showed the above abnormalities, although there
      were some quantitative differences between the two groups. We suggest these
      spatial errors arise because the cerebellum contributes either directly or
      indirectly to preparatory motor processes which, based on limb proprioceptive and
      retinal information, compute the pattern of muscle activity required to launch
      the limb accurately towards a target. Patients were largely successful at using
      visual guidance to make midflight adjustments to their movements in order to
      improve accuracy. This manifested as a reduction in spatial variability between
      repeat paths as the target was approached and a reduction in constant error.
      However, the visual correction mechanism did not appear normal. Under visual
      guidance, the end-phase of movement was often prolonged and characterized by
      excessive deviations or direction changes in the path. These deviations may be
      the expression of a visual guidance system producing corrections which themselves
      contain error requiring further correction. Thus, this process may be abnormal
      for the same reason that the initial pattern of muscle activity is misjudged.

PMID- 9549512
TI  - Electrical stimulation over muscle tendons in humans. Evidence favouring
      presynaptic inhibition of Ia fibres due to the activation of group III tendon
      afferents.
AB  - Electrical stimulation over muscle tendons produces a transient suppression of
      voluntary EMG activity; its onset latency is approximately 55 ms in the forearm
      extensor muscles. This phenomenon has been attributed to the activation of a
      polysynaptic inhibitory pathway originating from Ib afferent fibres. To clarify
      its origin we conducted several experiments in 10 normal healthy subjects. The
      EMG silence after tendon stimulation appeared at relatively high stimulus
      intensities (> 50 mA); conditioning cutaneous stimulation left it unchanged, and
      the inhibition had a short recovery cycle (50 ms). Tendon stimulation still
      evoked EMG suppression during an ischaemic block of fast-conducting afferents.
      The motor potentials evoked by transcranial magnetic stimulation of the motor
      cortex during the EMG silence remained almost unchanged, whereas the H reflex was
      strongly inhibited. Hence we conclude that tendon stimulation activates slow
      conducting tendon afferents, possibly group III fibres, connected not through a
      polysynaptic pathway originating from Ib afferents but through an oligo- or
      disynaptic inhibitory circuit. The EMG suppression after tendon stimulation
      probably represents a dysfacilitation of the alpha-motor neurons due to
      presynaptic inhibition of Ia fibres produced by tendon afferent input to the
      spinal cord.

PMID- 9549513
TI  - Cranial nerve syndrome in thrombosis of the transverse/sigmoid sinuses.
AB  - Cerebral venous thrombosis (CVT) is a cerebrovascular disease associated with a
      wide variety of clinical signs and symptoms, which may often delay appropriate
      diagnosis. Single or multiple cranial nerve palsies (III-VIII) without evidence
      of other signs and symptoms have not, so far, been considered a relevant syndrome
      of CVT. This event turned out to be a characteristic finding in five patients
      with thrombosis of the ipsilateral transverse/sigmoid sinus, who were recruited
      prospectively over a 14-month period. The diagnosis was supported by non-invasive
      MRI with the application of a newly developed subtraction technique. In view of
      the considerable mimics of the syndrome, and the long-standing need for
      conventional angiography to confirm the disease, it is likely to have been
      underestimated in the past; since appropriate treatment seems possible the
      diagnosis and utility of early MR venography should be considered in patients
      with single or multiple cranial nerve lesions of uncertain aetiology.

PMID- 9549514
TI  - Transcranial Doppler detected cerebral microembolism following carotid
      endarterectomy.

PMID- 9549515
TI  - Transcranial magnetic stimulation.

PMID- 9549516
TI  - Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy
      associated with deafness in gypsies. Clinical, electrophysiological and nerve
      biopsy findings.
AB  - A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was
      designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town
      where the initial cases were found. It was subsequently identified in other gypsy
      communities. The disorder, which is of autosomal recessive inheritance, was
      mapped to chromosome 8q24. It begins consistently in the first decade of life
      with gait disorder followed by upper limb weakness in the second decade and, in
      most subjects, by deafness which is most often first noticed in the third decade.
      Sensory loss affecting all modalities is present, both this and the motor
      involvement predominating distally in the limbs. Skeletal deformity, particularly
      foot deformity, is frequent. Severely reduced motor nerve conduction velocity
      indicates a demyelinating basis, which was confirmed by nerve biopsy. The three
      younger patients biopsied showed a hypertrophic 'onion bulb' neuropathy. The
      hypertrophic changes were not evident in the oldest individual biopsied and it is
      likely that they had regressed secondarily to axon loss. In the eight cases in
      which brainstem auditory evoked potentials could be recorded, the results
      suggested demyelination in the eighth cranial nerve and also abnormal conduction
      in the central auditory pathways in the brainstem. As no myelin genes are known
      to be located at chromosome 8q24, the disorder may involve a gene for a novel
      myelin protein or be due to an abnormality of axon-Schwann cell signalling.

PMID- 9549517
TI  - Different activation patterns in the visual cortex of late and congenitally blind
      subjects.
AB  - A key issue in developmental neuroscience is the role of activity-dependent
      mechanisms in the epigenetic induction of functional organization in visual
      cortex. Ocular blindness and ensuing visual deprivation is one of the rare models
      available for the investigation of experience-dependent cortical reorganization
      in man. In a PET study we demonstrate that congenitally blind subjects show task
      specific activation of extrastriate visual areas and parietal association areas
      during Braille reading, compared with auditory word processing. In contrast,
      blind subjects who lost their sight after puberty show additional activation in
      the primary visual cortex with the same tasks. Studies in blind-raised monkeys
      show that crossmodal responses in extrastriate areas can be elicited by
      somatosensory stimulation. This is consistent with the crossmodal extrastriate
      activations elicited by tactile processing in our congenitally blind subjects.
      Since primary visual cortex does not show crossmodal responses in primate
      studies, the differential activation in late and congenitally blind subjects
      highlights the possibility of reciprocal activation by visual imagery in subjects
      with early visual experience.

PMID- 9549518
TI  - The long-term effect of intravenous immunoglobulin treatment in multifocal motor
      neuropathy.
AB  - We studied the long-term effect of intravenous immunoglobulin (IV Ig) treatment
      in seven patients with multifocal motor neuropathy. In six patients, treatment
      with a full IV Ig course (0.4 g/kg for 5 consecutive days) improved muscle
      strength but for not longer than 12 weeks. These patients received IV Ig
      maintenance treatment consisting of one infusion every week for 2-4 years. One
      patient in whom the effect of the initial full IV Ig treatment lasted for more
      than 1 year received incidental IV Ig treatment when muscle strength
      deteriorated. In all patients IV Ig treatment had a beneficial effect on most
      muscle groups during the follow-up period. However, in three of the seven
      patients muscle strength deteriorated during IV Ig maintenance treatment in four
      of the 28 muscle groups that had initially shown an improvement of muscle
      strength after the start of IV Ig treatment, and in two muscle groups with normal
      strength at the start of IV Ig treatment. The electrophysiological follow-up
      studies indicated that there was an improvement of conduction block, but also
      that there were new sites of conduction block and ongoing axonal degeneration
      during IV Ig maintenance treatment.

PMID- 9549519
TI  - Transcranial magnetic stimulation over the posterior cerebellum during smooth
      pursuit eye movements in man.
AB  - Recent neurophysiological experiments in the monkey have demonstrated that the
      flocculus and the posterior vermis, lobules VIc-VII (oculomotor vermis), are
      involved in the generation of pursuit eye movements. Whereas the functions of the
      flocculus in the control of smooth pursuit have been intensively investigated,
      sufficient data are not available for a profitable discussion of the functions of
      the oculomotor vermis in the control of smooth pursuit. We previously indicated
      that the posterior vermis can be electrically stimulated by a focal transcranial
      magnetic stimulation (TMS) device through the skull in man, and that focal TMS of
      the posterior vermis can modulate saccadic eye movements. In this study we
      investigated the effects of cerebellar stimulation on smooth pursuit metrics in
      man using a focal TMS device. Focal TMS was applied over the posterior cerebellum
      in an area approximately 7 mm lateral and caudal to the inion, where saccadic eye
      movements are modulated by TMS, during horizontal smooth pursuit elicited by a
      step-ramp target with a constant velocity of 15 degrees/s in four normal
      subjects. The TMS device was triggered after the onset of smooth pursuit during
      the initial acceleration phase (latency range = 40-80 ms) or the steady-state
      tracking phase (latency range = 300-340 ms). We investigated the effect of TMS on
      the velocity and acceleration of smooth pursuit. For smooth pursuit directed
      ipsilateral to the stimulation side (ipsiversive), focal TMS of the posterior
      cerebellum produced abrupt acceleration of pursuit in both initial acceleration
      and steady-state tracking phases. On the other hand, TMS produced abrupt
      deceleration of contraversive pursuit in both initial acceleration and steady
      state tracking phases. These findings suggest that the posterior vermis controls
      smooth pursuit velocity in a direction-selective manner in both initial
      acceleration and steady-state tracking phases.

PMID- 9549520
TI  - Transcranial stimulation excites virtually all motor neurons supplying the target
      muscle. A demonstration and a method improving the study of motor evoked
      potentials.
AB  - Transcranial stimulation has become an established method in the evaluation of
      corticospinal tract function. Clinical studies mainly address slowing of
      conduction through measurement of increased central conduction time (CCT) and
      'failures' of conduction through observation of marked reductions in the size of
      the motor evoked potential (MEP). While CCT is of great interest in detecting
      subclinical slowing of conduction, the method discloses only gross failures of
      conduction, since the size of the MEP varies markedly between normal subjects and
      from one stimulus to another, leading to a broad range of normal values.
      Furthermore, transcranial stimulation does not appear to achieve depolarization
      of all spinal motor neurons leading to the target muscles, since in most normal
      subjects MEPs are smaller in amplitude than the responses evoked by peripheral
      nerve stimulation. We have developed a triple stimulation technique (TST) which,
      through two collisions, links central to peripheral conduction and suppresses
      desynchronization of MEPs. This technique shows that transcranial stimulation
      does achieve depolarization of all, or nearly all, spinal motor neurons supplying
      the target muscle in healthy subjects. Our data thus demonstrate that the
      amplitudes of MEPs are (i) smaller than those of peripheral responses, mostly due
      to phase cancellation of the action potentials caused by the desynchronization
      occurring within the corticospinal tract or at spinal cell level and (ii)
      variable between normal subjects and from one stimulus to another, mostly due to
      variability of this desynchronization. This technique provides new insights into
      normal corticospinal tract conduction. It will improve detection and
      quantification of central motor conduction failures.

PMID- 9549521
TI  - Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's
      disease.
AB  - The aim of this study was to compare, retrospectively, the value of chronic
      bilateral stimulation of the internal globus pallidus (GPi) and the subthalamic
      nucleus (STN) in patients with young onset Parkinson's disease. We selected 13
      consecutive patients with similar characteristics at the time of surgery: age at
      onset < 40 years, disabling motor fluctuations (Hoehn and Yahr stage 4 or 5 in
      off-drug phases) and levodopa-induced dyskinesias (LID). Eight patients were
      operated on in the STN and five in the GPi. The Unified Parkinson's Disease
      Rating Scale (UPDRS), timed motor tests and a LID scale were compared in on- and
      off-drug conditions before surgery and 6 months after surgery on stimulation
      using the chronic electrical parameters found to improve best the motor state of
      the individual patient, without adverse effects. In off-drug phases, the motor
      score of the UPDRS was improved by 71% with STN stimulation and by 39% with GPi
      stimulation on average. This difference was statistically significant (P < 0.05).
      Whereas rigidity and tremor showed good improvement in both groups, the decrease
      in the akinesia score was more pronounced in the STN group. In the STN group, the
      improvement of all motor symptoms was very close, or equal, to the best levodopa
      response. Thus the levodopa test was predictive of outcome. The improvement in
      off-drug period motor handicap allowed a decrease in the levodopa-equivalent dose
      only in the STN group (-56%). The voltage, frequency and pulse width used for
      chronic stimulation were lower in the STN group. In the on-drug phases there was
      a marked improvement in LID in the GPi group, as measured by the dyskinesias
      score during an acute levodopa test, whereas there was only a small decrease in
      the STN group (P < 0.05). However, in the long term, the reduction of levodopa
      dosage in the STN group led to an indirect reduction of LID similar to that in
      the GPi group during activities of everyday life. In conclusion, the overall
      results favour the neurosurgical treatment of Parkinson's disease by stimulating
      the STN rather than the GPi.

PMID- 9549522
TI  - The role of the SCA2 trinucleotide repeat expansion in 89 autosomal dominant
      cerebellar ataxia families. Frequency, clinical and genetic correlates.
AB  - The spinocerebellar ataxia type 2 (SCA2) is caused by a trinucleotide (CAG)
      expansion in the coding region of the ataxin 2 gene on chromosome 12q.89 families
      with autosomal dominant cerebellar ataxia (ADCA) types I, II and III, and 47
      isolated cases with idiopathic late onset cerebellar ataxia (ILOCA), were
      analysed for this mutation. The identification of the SCA2 mutation in 31 out of
      38 families with the ADCA I phenotype, but in none of those with ADCA II, ADCA
      III or ILOCA confirms the specificity of this mutation. A clinical comparison of
      the ADCA I patients with the three known mutations (SCA1, -2 or -3) highlights
      significant differences between the groups; SCA2 patients tended to have a longer
      disease duration, a higher frequency of slow saccades and depressed tendon
      reflexes. However, these neurological signs were also seen in an ADCA I family in
      which the SCA2 mutation was not identified, illustrating the importance of a
      direct genetic test. The SCA2 families were from different geographical and
      ethnic backgrounds. However, haplotype analysis failed to show evidence of a
      founder mutation, even in families from the same geographical origin. The range
      of normal alleles varied from 17 to 30 CAG repeats and from 35 to 51 repeats for
      the pathological alleles. Similar to the other diseases caused by unstable
      trinucleotide repeats, a significant inverse correlation has been found between
      the number of repeats and age of onset, and there is a significantly higher
      paternal instability of repeat length on transmission to offspring. The SCA2
      mutation is the most frequent amongst ADCA I patients, accounting for 40%,
      compared with SCA1 and SCA3 which account for 35% and 15%, respectively.

PMID- 9549523
TI  - Macrophage differentiation antigens in acute and chronic autoimmune
      polyneuropathies.
AB  - The pathological differential diagnosis between potentially treatable autoimmune
      neuropathies and degenerative neuropathies is often difficult if major T-cell
      infiltrates are absent in sural nerve biopsies. Since it is suggested that
      macrophages play a central pathogenetic role in inflammatory neuropathies, we
      investigated the expression of macrophage differentiation antigens associated
      with acute (MRP14 and 27E10 antigens) and more chronic inflammation (MRP8 and
      25F9 antigens) in 76 sural nerve biopsies from patients with Guillain-Barre
      syndrome, chronic inflammatory demyelinating polyneuropathy, other inflammatory
      neuropathies, hereditary neuropathies and normal sural nerves. Macrophage
      differentiation antigens were immunocytochemically detected in a majority of
      inflammatory biopsies but rarely in non-inflammatory disease controls and normal
      looking nerves. Quantification of labelled endoneurial cells revealed
      significantly elevated cell counts compared with controls. In individual
      biopsies, elevated levels of one differentiation antigen were not necessarily
      associated with high expression of the other antigens, pointing to functional
      heterogeneity of endoneurial macrophages. Endoneurial cell counts for at least
      one of the differentiation markers that were greater than in any of the non
      inflammatory control nerves were found in two-thirds of all inflammatory
      biopsies, whereas T-cell counts and in particular total macrophage counts were
      less sensitive in picking up biopsies from patients with inflammatory
      neuropathies. Antibodies to macrophage differentiation antigens are additional
      simple and helpful diagnostic tools in differentiating autoimmune from non
      inflammatory neuropathies in sural nerve biopsies.

PMID- 9549524
TI  - Matrix metalloproteinase expression during experimental autoimmune neuritis.
AB  - Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barre
      syndrome. We have shown recently that BB-1101, a broad-spectrum matrix
      metalloproteinase (MMP) inhibitor, prevents development of EAN when given from
      the day of immunization and, more important clinically, reduces disease severity
      when given from symptom onset. This suggests the involvement of MMP activity in
      the pathogenesis of EAN. However, the exact function and expression patterns of
      MMPs in acute inflammation of the PNS have not been investigated. MMP-like
      enzymes are also involved in the processing of tumour necrosis factor-alpha (TNF
      alpha), which has been implicated previously in the pathology associated with
      EAN. In the present study we investigated the profile of MMP and TNF-alpha
      expression and their localization in sciatic nerve tissue during EAN, using a
      semiquantitative competitive reverse transcriptase-coupled polymerase chain
      reaction and immunohistochemistry. In the normal rat PNS, four of the 10 MMPs
      studied were constitutively expressed and four MMPs were differentially regulated
      during EAN. Expression of TNF-alpha was elevated at peak disease severity and
      localized to Schwann cells, macrophages and endoneurial blood vessels. Expression
      levels of 92 kDa gelatinase and stromelysin-1 were significantly increased early
      in the development of EAN and continued to rise, peaking at day 15 coincident
      with maximum disease severity. Schwann cells and endothelial cells were the main
      cellular source of these enzymes. Prominent infiltration of inflammatory cells
      into the sciatic nerve was concordant with a significant increase in the
      expression levels of matrilysin and macrophage metalloelastase. Both matrilysin
      and macrophage metalloelastase were detected in invading macrophages, T
      lymphocytes and resident Schwann cells. The selective upregulation of specific
      MMPs during EAN and their varied cellular localization suggests that MMPs play a
      multifactorial role in the aetiology of EAN. Activity of MMPs could participate
      in the disruption of the blood-nerve barrier, breakdown of the myelin sheath, the
      release of TNF-alpha, and facilitate leukocyte invasion into the PNS. These
      observations highlight MMPs as potential targets for therapeutic intervention in
      acute peripheral neuropathies, such as Guillain-Barre syndrome.

PMID- 9549525
TI  - The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A
      10-year follow-up.
AB  - A definitive diagnosis of multiple sclerosis cannot be made at presentation on
      patients with a clinically isolated syndrome of the optic nerve, spinal cord or
      brainstem suggestive of demyelination, as dissemination in time is not
      established. To determine the long-term risk of abnormalities on brain MRI for
      the development of multiple sclerosis and disability we performed a 10-year
      follow-up on 81 such patients who had T2-weighted brain MRI at presentation.
      Initial brain MRI was abnormal in 54 (67%). Follow up of those patients with an
      abnormal MRI revealed progression to clinically definite multiple sclerosis in 45
      out of 54 (83%), of whom 11 (20%) had relapsing/remitting disease (EDSS > 3), 13
      (24%) secondary progressive and 21 (39%) benign (relapsing/remitting with EDSS <
      or = 3) disease. For those with a normal MRI progression to clinically definite
      multiple sclerosis occurred in only three out of 27 (11%), all benign. There was
      a significant relationship between the number of lesions at presentation and both
      EDSS (r = 0.45, P < 0.001) and the type of disease at follow-up (P < 0.0001).
      Brain MRI at presentation with a clinically isolated syndrome is predictive of
      the long-term risk of subsequent development of multiple sclerosis, the type of
      disease and extent of disability.

PMID- 9549526
TI  - Training improves the speed of aimed movements in Parkinson's disease.
AB  - In this study, the extent to which bradykinesia in patients with idiopathic
      Parkinson's disease can be influenced by practice and by specific training
      strategies was investigated. Fifteen patients with Parkinson's disease tested
      after withdrawal of anti-Parkinson medication, and 15 matched control subjects,
      practised a ballistic aiming task. Performance was tested before, during and
      after training and again 1 h later. The Parkinson's disease patients and control
      subjects were randomly assigned to one of two training schedules, practising with
      or without rhythmic auditory cues. At baseline, the Parkinson's disease patients
      showed longer movement times, with a marked decrease in maximum acceleration and
      deceleration in the initial open-loop phase compared with those of the control
      subjects. With training, they were able to make significant improvement in the
      speed of aimed movements, particularly in the early movement phase, without any
      deterioration in accuracy. These effects transferred to an untrained limb and
      were at least partially maintained after a 1-h delay. While patients remained
      impaired relative to control subjects at all phases of training and follow-up,
      the patients' performance at the end of training did not differ significantly
      from the control subjects' baseline function. Contrary to expectation, rhythmic
      auditory cues did not enhance improvement in the speed of aimed movements in
      either patients or control subjects. If anything, less improvement was shown in
      the cued groups, although there were suggestions that the aiming skill was
      retained better over the delay period. The results demonstrate preserved
      abilities to improve speed of single ballistic aiming movements in Parkinson's
      disease patients and the possibility of reducing bradykinesia by training.

PMID- 9549527
TI  - Relationships between timing of muscle excitation and impaired motor performance
      during cyclical lower extremity movement in post-stroke hemiplegia.
AB  - We used an ergometer pedalling paradigm to relate abnormalities in the timing of
      muscle excitation to the impaired ability to perform mechanical work in the
      plegic lower limbs of persons with hemiplegia. The EMGs of seven leg muscles and
      pedal forces were measured bilaterally during pedalling for 15 persons with
      hemiplegia and 12 neurologically intact age-matched control subjects. Subjects
      were asked to pedal at a moderate workload (135 J) and cadence (40 r.p.m.). While
      intersubject variability was high, the external mechanical work output of the
      plegic leg was significantly less (from 79.6% to -28.9% of the work produced by
      average leg of control subjects) as a result of less positive work and more
      negative work being done. The timing of EMG in individual plegic limb muscles
      exhibited two distinct types of abnormalities that were significantly correlated
      with this lesser work production: prolonged excitation in the vastus medialis and
      phase-advanced excitation (both early initiation and early termination) in the
      rectus femoris and semimembranosus. These results suggest that muscles were
      differently affected depending on their function, external power-producing
      muscles (e.g. vastus medialis) showing prolonged excitation and muscles that
      normally maintain crank progression during limb transitions (e.g.
      semimembranosus) showing phase-advanced excitation.

PMID- 9549528
TI  - Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak
      dose dyskinesia.
AB  - We have studied the regional cerebral blood flow (rCBF) changes induced by the
      execution of a finger-to-thumb opposition motor task in the supplementary and
      primary motor cortex of two groups of parkinsonian patients on L-dopa medication,
      the first one without L-dopa induced dyskinesia (n = 23) and the other with
      moderate peak-dose dyskinesia (n = 15), and of a group of 14 normal subjects.
      Single photon emission tomography with i.v. 133Xe was used to measure the rCBF
      changes. The dyskinetic parkinsonian patients exhibited a pattern of response
      which was markedly different from those of the normal subjects and non-dyskinetic
      parkinsonian patients, with a significant overactivation in the supplementary
      motor area and the ipsi- and contralateral primary motor areas. These results are
      compatible with the hypothesis that an hyperkinetic abnormal involuntary
      movement, like L-dopa-induced peak dose dyskinesia, is due to a disinhibition of
      the primary and associated motor cortex secondary to an excessive outflow of the
      pallidothalamocortical motor loop.

PMID- 9549529
TI  - Disseminating and applying best evidence.

PMID- 9549530
TI  - Heparin in the home: risks and benefits.

PMID- 9549531
TI  - Hospital-in-the-home care: is it worth the hassle?

PMID- 9549532
TI  - Reforming Medicare.

PMID- 9549533
TI  - Use of systematic reviews of randomised trials by Australian neonatologists and
      obstetricians.
AB  - OBJECTIVE: To determine what proportion of Australian neonatologists and
      obstetricians report using systematic reviews of randomised trials. DESIGN: Cross
      sectional survey using structured telephone interviews. SETTING: Australian
      clinical practice in 1995. PARTICIPANTS: 103 of the 104 neonatologists in
      Australia (defined as clinicians holding a position in a neonatal intensive care
      unit); a random sample of 145 members of the Royal Australian College of
      Obstetricians and Gynaecologists currently practising in Australia. MAIN OUTCOME
      MEASURES: Information sources used in clinical practice; reported awareness of,
      access to and use of systematic reviews, and consequent practice changes.
      RESULTS: Response rates were 95% (neonatologists) and 87% (obstetricians); 71
      neonatologists (72%) and 55 obstetricians (44%) reported using systematic
      reviews, primarily for individual patient care. Databases of systematic reviews
      were used with a median frequency of once per month. Among neonatologists,
      systematic reviews were used more commonly by those who were familiar with
      computers, attended professional meetings, and had authored research papers.
      Among obstetricians, they were used more commonly by those who were familiar with
      computers, had less than 10 years' clinical experience, attended more deliveries,
      and were full-time staff specialists in public hospitals. Of neonatologists who
      reported using systematic reviews, 58% attributed some practice change to this
      use. For obstetricians, the corresponding figure was 80%. CONCLUSIONS: There is
      evidence that Australian neonatologists and obstetricians use systematic reviews
      and modify their practice accordingly. Dissemination efforts can benefit from
      knowledge of factors that predict use of systematic reviews.

PMID- 9549534
TI  - Dalteparin for deep venous thrombosis: a hospital-in-the-home program.
AB  - OBJECTIVE: To assess the efficacy, safety and cost savings of home treatment of
      lower-limb deep venous thrombosis (DVT). SETTING: A hospital-in-the-home
      treatment program. PATIENTS: One hundred patients with acute lower limb DVT (53
      proximal, 47 distal), and no contraindication to home treatment, were entered
      into the program from March 1995 to February 1997. INTERVENTION: All patients
      received dalteparin, 200 units/kg subcutaneously, once daily for a minimum of
      five days, with commencement of oral anticoagulation (warfarin) on Day 2.
      Patients with proximal DVT had lung ventilation-perfusion scans performed and
      were admitted to hospital for at least 24 hours. Patients with distal DVT were
      discharged directly to home treatment. MAIN OUTCOME MEASURES: Clinical responses
      and the results of sequential duplex ultrasonography at one week, one month,
      three months and six months. RESULTS: There were no major, but six minor,
      bleeding complications, two of which led to dalteparin being withdrawn. Sixteen
      patients had lung ventilation-perfusion scans showing a high probability of
      pulmonary embolism. All were asymptomatic, and follow-up for at least three
      months showed no symptomatic thromboembolic events. Duplex ultrasonography showed
      progression of thrombosis in the first week of therapy in 13.2% of distal and
      2.7% of proximal thromboses. Thereafter, distal DVT improved at a much greater
      rate than proximal DVT; after six months complete resolution was seen in 60.7% of
      distal and 18.5% of proximal thromboses, respectively. Cost saving was $197 per
      bed-day equivalent compared with inpatient care. At 15 months' follow-up,
      swelling and/or pain was reported by 49% of patients with distal DVT and 66% of
      those with proximal DVT. CONCLUSIONS: Once-daily dalteparin therapy for DVT in a
      hospital-in-the-home setting was safe, efficacious and cost effective. However,
      DVT resolution is a slow process, with significant long term morbidity.

PMID- 9549535
TI  - How safe is hospital-in-the-home care?
AB  - OBJECTIVE: To describe the rate of negative, unexpected and adverse events
      associated with hospital-in-the-home (HIH) care in an established unit, and to
      validate indicators of safety for HIH care. DESIGN: Prospective descriptive
      survey. PATIENTS AND SETTING: 231 patients, who would otherwise have required
      hospitalisation, accepted for acute home-based care by the HIH unit at Frankston
      Hospital, a 350-bed hospital serving a population of 240,000 on the south-eastern
      boundary of Melbourne. MAIN OUTCOME MEASURES: The following indicators of safety:
      patient telephone calls to the on-call service; unscheduled staff callout to
      patients' homes; return to hospital during an HIH admission; and return to
      hospital after discharge. RESULTS: 190 acute admissions were examined. Planned
      same-day admissions were uneventful and excluded from the analysis. The therapies
      provided were intravenous therapy (mainly antibiotics), anticoagulation, and
      wound care. Unplanned patient telephone calls were received in 6.3% of
      admissions; 5.8% of acute admissions required an unscheduled staff home
      attendance; 4.2% of episodes resulted in a return to hospital, of which 2.6%
      required continued care in hospital; 2.2% of episodes resulted in a return to
      hospital within 14 days of discharge for a related problem. The rate of
      iatrogenic adverse events was 3.5%. CONCLUSIONS: HIH care is very safe. This
      study may help define safety standards for HIH care so that future studies can
      compare them with those of traditional inpatient care.

PMID- 9549536
TI  - Infant pertussis deaths in New South Wales 1996-1997.
AB  - Since 1996, south-eastern Australia has been experiencing a pertussis epidemic
      which has resulted in the deaths of several infants, including four from NSW in
      the 12 months to July 1997. All were less than six weeks of age and died from
      overwhelming cardiovascular compromise despite intensive care support. This
      excessive infant mortality from a preventable disease demonstrates the need for
      better pertussis immunity in the community and for erythromycin treatment of all
      suspected cases and family contacts, especially infants.

PMID- 9549537
TI  - Towards an improved and more cost effective health system for Australia.
AB  - A new health system is proposed, based on the best aspects of the current system
      but with built-in incentives for containing costs. Universal cover is retained
      and access to the hospital system is improved. The division of health
      responsibilities between Federal and State governments is greatly simplified and
      the proposed system could be readily implemented.

PMID- 9549538
TI  - Unemployment and health: the healthcare system's role.
AB  - Experts from the South Western Sydney Area Health Service and the University of
      New South Wales say there are few reports of healthcare interventions to address
      the impact of unemployment on health. They outline possible strategies, which
      include providing accessible and appropriate healthcare; developing the
      healthcare system's capacity to deal with the health problems of unemployed
      people; collaborating with other agencies and sectors working on this issue;
      acting as an advocate for unemployed people; undertaking research; and providing
      training, work experience and employment opportunities within the healthcare
      system. Long term solutions lie in increasing employment and training
      opportunities. Nevertheless, there is a clear role for the healthcare system in
      reducing the health impacts of unemployment and ensuring that poor health does
      not act as a barrier to returning to work.

PMID- 9549539
TI  - Death is a journey to be undertaken.

PMID- 9549540
TI  - Assessing and managing old age psychiatric disorders in community practice.

PMID- 9549541
TI  - Brain tumours and mobile phones?

PMID- 9549542
TI  - Brain tumours and mobile phones?

PMID- 9549543
TI  - Brain tumours and mobile phones?

PMID- 9549544
TI  - Brain tumours and mobile phones?

PMID- 9549546
TI  - Reproductive medicine and the social state of childlessness.

PMID- 9549547
TI  - Dwindling supplies of anti-D.

PMID- 9549548
TI  - Dwindling supplies of anti-D.

PMID- 9549549
TI  - A study of 100 anabolic-androgenic steroid users.

PMID- 9549550
TI  - Copper-salicylate gel for pain relief in osteoarthritis.

PMID- 9549551
TI  - A mnemonic for thrombophilia screening tests.

PMID- 9549553
TI  - Zinc: a critical nutrient in growth and development.

PMID- 9549552
TI  - The choice of antibacterial drugs.

PMID- 9549554
TI  - Social inequality and general practitioner utilisation: assessing the effects of
      financial barriers on the use of care by low income groups.
AB  - AIMS: To evaluate the extent to which financial barriers are still important
      deterrents to the utilisation of primary care by low income groups and to examine
      whether the willingness of patients to switch doctors is associated with ability
      to pay. METHOD: A practice and a population survey was used to compare the
      importance of price barriers, patient satisfaction and utilisation rates in two
      low income areas of Christchurch. Comparisons are made on the basis of gender,
      age, perceived health status, housing tenure, benefit status, income and
      ethnicity. RESULTS: Despite the introduction of the Community Services Card,
      delays in using services because of the cost of care remain significant for many
      groups of patients, including cardholders themselves. The removal of price
      barriers at the free clinic raised utilisation rates for all groups. Patterns of
      use at the free clinic show a consistent inverse relationship between income and
      consultation rates. However, this was not evident among patients in the
      population sample who continued to use fee-for-service providers. Further, the
      results do not support arguments that patients are insensitive to price when
      changing their doctors. CONCLUSIONS: Despite the removal of part-charges for
      children, financial barriers remain significant for many low income adults. To a
      large extent these barriers reflect the nature of welfare reform, particularly
      the detrimental effects of pro-market housing policies in limiting the disposable
      incomes of poorer New Zealanders.

PMID- 9549555
TI  - Compliance with guidelines for the investigation and management of patients with
      suspected pulmonary embolism at Christchurch Hospital.
AB  - AIMS: (1) To assess the level of compliance of clinicians at Christchurch
      Hospital with published local guidelines for the diagnostic management of
      indeterminate lung scans and for the treatment of pulmonary embolism. (2) To
      evaluate diagnostic outcomes and the methods used to arrive at the diagnosis.
      METHODS: Retrospective case analysis of 94 consecutive cases of suspected
      pulmonary embolism referred for a lung scan after August 1993 and a further 70
      consecutive cases referred after August 1995. RESULTS: Few clinicians followed
      the recommendations for the further assessment of indeterminate lung scans.
      Pulmonary angiography was rarely performed and serial femoral ultrasound was
      never employed. The majority of patients diagnosed with pulmonary embolism did
      not have a high probability ventilation/perfusion (VQ) scan or a pulmonary
      angiogram to support the diagnosis. The use of heparin was overcautious and
      inconsistent. Major divergences from recommendations were observed in over 50% of
      cases in which heparin was used to treat pulmonary embolism. CONCLUSIONS: This
      audit has uncovered a wide diversity of practice in many aspects of the
      assessment and management of pulmonary embolism and significant deviations from
      the published guidelines. Underutilisation of objective imaging methods for
      establishing the diagnosis implies overreliance on clinical impressions, which
      are known to be unreliable. A review of the guidelines and further educational
      initiatives are indicated.

PMID- 9549556
TI  - The cost of childhood immunisation in general practice.
AB  - AIM: To estimate the cost, to general practices in the Wellington Immunisation
      Network, of the audit process of recalling and immunising children according to
      the New Zealand Immunisation Schedule. METHOD: Practices recorded all clinical
      and clerical time spent on immunisation as well as the materials used throughout
      one audit cycle. Staff time and materials were costed directly. Practice
      overheads were apportioned to immunisation according to the actual time spent on
      each of the tasks relating to immunisation relative to the total staff hours at
      the practice. RESULTS: The average cost of immunising a child who attended a non
      capitated practice after a single reminder or recall was $15.15. The cost to the
      practice after taking the practice nurse subsidy and GMS into account was $8.51.
      The cost of immunising children who were not immunised at the first recall
      increased in proportion to the number of recall reminders. The annual average
      cost of immunisation to practices in the study exceeded the revenue obtained from
      the Immunisation Benefit. CONCLUSION: Overall, given the frequency of recall
      reminders, there was a net cost to practices for childhood immunisation after
      deducting the current immunisation benefit rate of $9.78 excluding GST. Thus, the
      practices in this study made a "loss" in carrying out childhood immunisations.

PMID- 9549557
TI  - A complaints management system: strengths and weaknesses.
AB  - AIMS: To describe the complaints management process in a base hospital and to
      outline its guiding principles. METHOD: A review and analysis of the complaints
      lodged during 1996 with the Complaints Management System of the hospital.
      RESULTS: There were 146 complaints lodged after 132,400 patient contacts. Overall
      resolution time was 14 days, but 24 appeals were lodged against the initial
      opinion and were all subsequently resolved satisfactorily. CONCLUSION: The
      complaints process should be user friendly, result in a quick response and be
      seen as a quality rather than a disciplinary tool.

PMID- 9549558
TI  - Monitoring of health research by ethics committees.
AB  - AIMS: All health related research carried out within New Zealand requires
      appraisal from an accredited ethics committee. The purpose of this project was to
      pilot an active monitoring programme and to assess the effectiveness of such a
      programme for future monitoring by ethics committees. METHODS: In this
      qualitative study interviews were undertaken by representatives from the
      Wellington and Manawatu-Whanganui ethics committees with principal investigators
      for sixteen research proposals which had been given ethical approval from the
      appropriate ethics committee. Issues discussed during the interviews included the
      protocol and any changes to the methods or research personnel, recruitment of
      participants, issues arising from informed consent, reporting of adverse events,
      funding and payment to researchers. Researchers were given the opportunity to
      provide feedback on the ethical review process and suggestions for improvement.
      RESULTS: The most significant deviation from the approved protocol concerned
      access to patient information. Some minor discrepancies between the approved
      protocols and subsequent research undertaken and the requirements for extending
      ethical approval of projects beyond the initial approval date were also
      discussed. CONCLUSIONS: The monitoring programme fulfilled an educational role,
      providing an opportunity for information sharing between ethics committees and
      researchers. An active monitoring programme by an ethics committee can detect
      deviations from the approved protocol beyond the current requirements for
      researchers to provide annual progress reports. Future monitoring should include,
      where relevant, access to consent forms and patients' notes.

PMID- 9549559
TI  - Ticlopidine induced agranulocytosis managed with granulocyte colony stimulating
      factor.

PMID- 9549561
TI  - Sporadic amoebic liver abscess in the North Island.

PMID- 9549560
TI  - Staphylococcus aureus highly resistant to mupirocin is now common in Auckland.

PMID- 9549562
TI  - Strongyloides stercoralis and severe pre-eclampsia.

PMID- 9549563
TI  - The hematological responses of rats exposed to conditions of simulated
      microgravity and acute exercise.
AB  - BACKGROUND: Although humans have experienced microgravity since 1961, it is
      unknown whether PaO2 or PaCO2 will change in humans or in animals exposed to
      similar conditions. Reports from subjects participating in long-term head down
      tilt studies indicate that PAO2 will decrease and PaCO2 will increase, presumably
      because of impairments in oxygen delivery and carbon dioxide transport. To
      investigate this topic with suspended (HDS) rats, we hypothesized that 14 d of
      HDS would lower resting PaO2 and elevate PaCO2 pressures when compared with
      control rats. Since returning astronauts, previously bed rested subjects, and
      suspended rats had exhibited decreases in maximum aerobic capacity, we predicted
      after 2 weeks of HDS, rats performing maximum exercise would demonstrate
      significant decreases in PaO2 and elevations in hydrogen ions. RESULTS: Blood gas
      results during HDS indicated PaO2 and PaCO2 partial pressures were significantly
      decreased during the first week of suspension. Maximal exercise significantly
      increased PaO2 pressures in both animal groups, but during exercise the suspended
      rats exhibited significant increases in lactic acid and hydrogen ion
      concentrations when compared with control animals. CONCLUSIONS: The suspended rat
      model effectively characterized PaO2 changes that have been reported for humans
      exposed to conditions of simulated microgravity. However, the decreases in VO2max
      reported for exercising humans and animals could not be explained by PaO2 changes
      and the rat model was not effective in predicting changes in blood PaCO2.
      RECOMMENDATIONS: NASA should encourage and support studies that characterize PaO2
      and PaCO2 change in humans and animals, in space and after they return to a 1-G
      environment.

PMID- 9549564
TI  - Pulmonary capillary blood volume during lower body negative pressure: effect of
      gender.
AB  - BACKGROUND: The purpose of this study was to examine the changes in pulmonary
      capillary blood volume (VC) in men and women during lower body negative pressure
      (LBNP). Additionally, the components of lung diffusion capacity were measured and
      evaluated for the effect of gender and LBNP. METHODS: There were 6 men and 6
      women who underwent a staged LBNP protocol to -40 mm Hg. The diffusion of the
      lung for carbon monoxide (DLCO) was determined at two levels of inspired oxygen
      (21% and 60%). DLCO was separated into the diffusion capacity of the membrane
      (DLM) and the diffusion capacity of blood. RESULTS: During supine rest, DLCO
      values for men were larger than for women and were 39.8 +/- 3.8 and 32.2 +/- 2.2
      ml.min-1.mm-1 Hg, respectfully. DLCO decreased equally with each stage of LBNP
      for men and women. VC during supine rest was greater for men (131 +/- 8 ml) than
      for women (92.7 +/- 7 ml). VC also declined with each stage of LBNP, and the
      decline was similar for men and women. DLM did not change with LBNP. CONCLUSION:
      The decrease in DLCO with LBNP is due to the reductions in thoracic blood volume
      in both men and women. These thoracic blood volume changes do not explain the
      previously reported reduced tolerances to LBNP for women because the reductions
      in thoracic blood volume were similar for men and women.

PMID- 9549565
TI  - The effects of moderately elevated ambient carbon dioxide levels on human
      physiology and performance: a joint NASA-ESA-DARA study--overview.

PMID- 9549566
TI  - The influence of CO2 in a space-like environment: study design.
AB  - For the operation of manned spacecraft, the removal of CO2 from the cabin
      atmosphere, produced by its inhabitants, is essential. This is accomplished by
      chemical absorption in a gas processing unit, a process which requires energy and
      consumables. Therefore, in terms of resource management, the CO2-level should be
      kept as high as possible. Otherwise, considering crew health and performance and
      also the interference with life science experiments, the CO2 load should be as on
      Earth, close to zero. In order to obtain more information about the permissible
      CO2 level for future space missions and also to clarify Space Station design
      criteria, NASA-ESA-DARA have initiated a ground-based simulation study with two
      different CO2 levels: 0.7% (first campaign) and 1.2% CO2 (second campaign). For
      this study the deep diving facility of DLR was used to provide atmospheric
      control and long-term habitation for the test subjects in studying the effect of
      increased CO2 on physiological and psychological functions. A number of
      experiments were implemented, which tested selected effects of raised CO2 on
      humans. Four male subjects stayed in the chamber for 26 d in each campaign, in
      order to perform the different tests in repeated trials, with the aim of
      evaluating possible long-term effects. CO2 was controlled by absorption with soda
      lime, flushing with fresh air and the addition of CO2, if necessary. Essentially,
      the CO2 produced by the subjects was used to maintain the level at 0.7 and 1.2%,
      respectively. Basic control of CO2 was carried out in the soda lime container of
      the Life Support System. In order to maintain the required level, the amount of
      gas flowing through the soda lime could be adjusted by a remote controlled
      bypass. With this set-up it was possible to keep CO2 at an average level between
      0.67 and 0.73% in the first campaign and between 1.17 and 1.23% in the second
      campaign. The results of the experiments support the current CO2 limits for space
      operations, insofar as values around 1% do not impose any severe restrictions to
      human habitation for at least several weeks, whereas life sciences experiments
      especially sensitive to CO2 influences have to be carefully evaluated for
      possible interferences.

PMID- 9549567
TI  - Effects of elevated carbon dioxide environment on calcium metabolism in humans.
AB  - BACKGROUND: Chronic respiratory acidosis induced by an elevated carbon dioxide
      (CO2) environment should provoke hypercalciuria with related total body and
      subsequent bone calcium losses. We examined this hypothesis in four healthy male
      volunteers, who were exposed during a 25-d period to an 0.7% CO2 environment
      within a deep diving isolation chamber. Three months later the same subjects were
      reexamined during a second campaign being exposed to a 1.2% CO2 atmosphere.
      METHODS: The subjects received a constant calcium intake (1.4 g.d-1) and vitamin
      D supplement (1000 IU.d-1) during both campaigns. Calcium balance (oral calcium
      intake minus urinary and fecal calcium output) was evaluated. Serum calcium
      concentrations and biomarkers of bone metabolism were measured, in order to
      evaluate bone turnover. Additionally, the response to an acute oral calcium load
      was examined as a sensitive measure of changes in calcium metabolism. RESULTS:
      Both, urinary calcium excretion (from 245 +/- 38 to 199 +/- 31 mg.d-1; mean +/-
      SE, 0.7% and 1.2%, respectively) and fecal calcium losses (from 1229 +/- 128 to
      996 +/- 62 mg.d-1) were significantly reduced in the higher (1.2%) CO2
      atmosphere. Although more calcium was retained in the body during the 1.2% than
      during the 0.7% CO2 campaign, serum calcium concentrations and biomarkers of bone
      formation were significantly lower in the higher CO2 campaign. Furthermore, bone
      resorption was slightly increased in the 1.2% experiment. CONCLUSION: Elevated
      CO2 atmosphere may dose-dependently preserve body calcium without a parallel
      improvement of bone substance.

PMID- 9549568
TI  - Effects of sustained low-level elevations of carbon dioxide on cerebral blood
      flow and autoregulation of the intracerebral arteries in humans.
AB  - Cerebral blood flow velocity (CBFv) was measured by insonating the middle
      cerebral arteries of four subjects using a 2 Mhz transcranial Doppler. Ambient
      CO2 was elevated to 0.7% for 23 d in the first study and to 1.2% for 23 d in the
      same subjects in the second study. By non-parametric testing CBFv was elevated
      significantly by +35% above pre-exposure levels during the first 1-3 d at both
      exposure levels, after which CBFv progressively readjusted to pre-exposure
      levels. Despite similar CBFv responses, headache was only reported during the
      initial phase of exposure to 1.2% CO2. Vascular reactivity to CO2 assessed by
      rebreathing showed a similar pattern with the CBFv increases early in the
      exposures being greater than those elicited later. An increase in metabolic rate
      of the visual cortex was evoked by having the subjects open and close their eyes
      during a visual stimulus. Evoked CBFv responses measured in the posterior
      cerebral artery were also elevated in the first 1-3 d of both studies returning
      to pre-exposure levels as hypercapnia continued. Cerebral vascular autoregulation
      assessed by raising head pressure during 10 degrees head-down tilt both during
      the low-level exposures and during rebreathing was unaltered. There were no
      changes in the retinal microcirculation during serial fundoscopy studies. The
      time-dependent changes in CO2 vascular reactivity might be due either to
      retention of bicarbonate in brain extracellular fluid or to progressive increases
      in ventilation, or both. Cerebral vascular autoregulation appears preserved
      during chronic exposure to these low levels of ambient CO2.

PMID- 9549570
TI  - The history of the United States Navy flight surgeon/naval aviator program.
AB  - Early in the history of aviation the need for a special kind of physician who
      could understand the physical and psychological problems encountered by flyers
      was well recognized. These physicians were called flight surgeons. In 1922, RADM
      W. A. Moffett, USN, the first Chief of the Bureau of Aeronautics and the "Father
      of Naval Aviation," called for a group of Navy medical officers to be trained as
      flight surgeons. He believed that all Navy flight surgeons should be trained as
      pilots "primarily in order that they may experience the emergencies and
      conditions that arise in flying." This article traces the history of the Navy
      flight surgeon/naval aviator. It chronicles the evolution of the Navy's flight
      surgeon/naval aviator program from the World War I doctor who flew seaplanes at a
      Naval Air Station in Italy to the present day flight surgeon/naval aviator who
      flys operational and test aircraft as a research pilot.

PMID- 9549569
TI  - Carotid artery dissection presenting as a painless Horner's syndrome in a pilot:
      fit to fly?
AB  - We describe a case of a middle-aged Caucasian pilot who presented to us with a
      painless left Horner's syndrome due to a focal dissection of the infra-petrous
      portion of the ipsilateral internal carotid artery. He did not suffer symptoms of
      cerebral ischemia at the time of onset, or during the following 2 yr. The
      Horner's syndrome persisted unchanged throughout follow-up. Serial magnetic
      resonance angiograms showed some regression of the focal stenosis at 12 mo, with
      no further change over the next 10 mo. The literature suggests that the risk of
      stroke after onset of dissection is usually in the first month, and the risk of
      recurrence of dissection is about 1% per year after the first year. Our patient
      was prescribed aspirin 300 mg.d-1, and certified to fly as or with a co-pilot
      commencing 1 yr after onset of his symptoms.

PMID- 9549571
TI  - Test your knowledge of brain lesions and aeromedical certification.

PMID- 9549572
TI  - A far from routine mission.

PMID- 9549573
TI  - GZ-induced neck injuries.

PMID- 9549574
TI  - Cementless primary total hip replacement. Four to eight year results with the
      Zweymuller-Alloclassic prosthesis.
AB  - One hundred and twenty-nine consecutive cementless primary total hip
      arthroplasties with Zweymuller-Alloclassic grit-blasted titanium components were
      evaluated prospectively at an average follow-up of 5.9 years. The clinical
      results were graded as excellent or good in 116 hips (90%), fair in 12, and poor
      in one due to a fracture of the femoral shaft at operation leading to early stem
      loosening and delayed ring loosening. Failure was defined as definite aseptic
      loosening, and the final survivorship at 8 years was 99.3% for the SL-stem, and
      99.1% for the CSF-threaded cup. These early results compare favourably with those
      of total hip arthroplasties using new cementing techniques.

PMID- 9549575
TI  - Prophylaxis for deep vein thrombosis with aspirin or low molecular weight dextran
      in Korean patients undergoing total hip replacement. A randomized controlled
      trial.
AB  - 150 Korean patients undergoing primary uncemented total hip replacement were
      randomized into 3 treatment groups for deep vein thrombosis (DVT) prophylaxis.
      Group A(50) were controls; Group B(50) received aspirin 1.2 g daily in 3 divided
      doses from 2 days before, to 14 days after surgery; Group C(50), received low
      molecular weight dextran 500 ml, infused intravenously at 50 ml/hour during
      surgery, and on each of the following 2 days. Contrast venograms were performed
      prior to surgery and 7-10 days after. The incidence of DVT was 20% in the control
      group, 12% in the aspirin group (p < 0.1 vs control), and 6% in the dextran group
      (p < 0.05 vs control). In patients developing DVT, the ratio of proximal to
      distal thrombi was increased in the control group as compared to treated groups
      (4:1 in the control group vs 1.5:1 in the treated groups). Both aspirin and
      dextran were well tolerated. Obesity (p < 0.05) and long-term administration of
      steroids (p < 0.05) were risk factors for deep vein thrombosis which reached
      statistical significance in the control group. Intraoperative venograms performed
      on 10 patients, showed that hip flexion (mean 40.4 degrees) plus adduction (mean
      11.5 degrees) plus internal rotation (mean 81.5 degrees), resulted in severe
      twisting or kinking of the femoral vein with stagnation of blood flow. Low
      molecular weight dextran significantly reduce the incidence of deep venous
      thrombosis and aspirin, though less effective, had a similar effect.

PMID- 9549576
TI  - Structural changes in blood vessels entering the growth plate during growth in
      rats.
AB  - We observed the structural changes in blood vessels entering the growth plates of
      the femur and tibia of rats during growth using scanning electron microscopy. The
      penetrating vessels had blind endings which were bulbous at a time when rats
      showed rapid skeletal development. With subsequent slowing of development, the
      density of the vessels decreased and the blind endings became short stumps. These
      changes were more prominent in the proximal femur than in the distal femur and
      proximal tibia. The present study indicates an intimate relation between
      endochondral ossification in the growth plate and the structure of the
      penetrating vessels.

PMID- 9549577
TI  - Malignant giant-cell tumours of bone. Clinico-pathological types and prognosis: a
      review of 29 cases.
AB  - Twenty-nine patients with malignant giant-cell tumours of bone (GCT) were
      followed-up for between 6 months and 18 years. Seventeen of the tumours were
      primary and 12 were due to malignant degeneration of initially benign lesions.
      The clinical features did not differ from those of benign GCT, except for a
      higher incidence in the distal tibia and sacrum. Anaplastic GCTs were included in
      the study because their clinical and radiographic features and prognosis were no
      different from those of the GCT grade III of Jaffe. Eighteen of the tumours were
      grade III, and 11 were anaplastic. This retrospective study was intended to
      assess the effects of chemotherapy and surgery for malignant GCT. Three treatment
      groups were selected, in which treatment was either by surgery alone, surgery
      plus chemotherapy, or radiotherapy alone.--The prognosis was poor and the 5 year
      tumour-free survival rate in the series was 50%. The prognosis was the same for
      primary as for secondarily malignant tumours. There was no statistical difference
      in survival between malignant grade III and anaplastic malignant tumours. The one
      year survival rate for patients treated by chemotherapy and surgery was
      statistically higher (chi2 test) than for persons treated by surgery alone.
      However, the five-year survival rate and the actuarial survival curves were not
      statistically different in the two groups (log rank test).--Chemotherapy appears
      to be of some value in the treatment of these malignant tumours but a larger
      series is required to confirm the efficacy of this approach.

PMID- 9549578
TI  - Expanding prostheses in conservative surgery for lower limb sarcoma.
AB  - Conservative resection of bone sarcoma in the lower limbs in children is very
      likely to be followed by a progressive problem of leg length inequality resulting
      from removal of the growth cartilage. To overcome this we have been using an
      expanding prosthesis and we report our experiences during the period 1985-1996.
      The prostheses are made of titanium and comprise 3 parts: an articular component,
      an expanding mechanism, and tibial and femoral stems. The degree of possible
      lengthening of the prostheses is virtually unlimited, and they can be inserted in
      children of 5 or more years of age. We report the use of 28 prostheses in
      patients aged from 5 to 18 years, of which 4 were tibial, 5 total femur, and 16
      distal femur. There were 6 Ewing's sarcoma, 21 osteosarcoma, and 1 synovial
      sarcoma. The average follow-up was for 5 years. Five patients died from their
      disease, and 21 benefited from an average lengthening of 2.6 cm (range: 2 mm-120
      mm). Using the Societe Europeenne des Tumeurs Osseouses (EMSOS) criteria, the
      functional results were excellent or very good in 16, fair in 7 and bad in 5.
      Five patients developed an infection; one required amputation and the others
      received a new expanding prosthesis. We conclude that an expanding prosthesis is
      an excellent alternative to amputation in young children. However, the risk of
      infection associated with repeat surgery has led us to develop a prosthesis which
      can be lengthened externally, without the need for reopening the wound.

PMID- 9549579
TI  - Treatment of chronic osteomyelitis using the Papineau technique.
AB  - From 1984 to 1994, 41 cases of chronic osteomyelitis were treated in Kinshasa by
      the Papineau technique; 75.5% were men and 24.5% women. The mean age was 28 years
      (range: 7-77), and the average duration of the infection was 3 years (range: 1
      month to 28 years). The aetiology was "trauma" in 53.5%, haematogenous in 44% and
      drepanocytosis in 2.5%. Infections of the femur and tibia each constituted 41.5%
      of the cases. Immobilisation was by external fixation in 44%, and by a cast in
      39%. Wound healing was complete after an average of 3 months with spontaneous
      healing, and in 4.5 months after skin grafting. Control of the infection and bone
      healing were obtained in 89% after a period of 3-7 months. We discuss the
      Papineau technique and the modifications which were required in Kinshasa.

PMID- 9549580
TI  - Primary pyogenic abscess of the psoas muscle.
AB  - During a six-year period, eleven persons with primary pyogenic abscess of the
      psoas muscle were treated at the Mackay Memorial Hospital. Five were males and
      six were females and their average age was 47.2 years (range 6-83 years). The
      abscess was identified by CT in 7 patients, MRI in 2 and ultrasonography in 1.
      One abscess was found during laparotomy. Treatment included extraperitoneal
      drainage of the abscess in 7 patients and CT guided aspiration in 3. One patient
      improved after antibiotic therapy and they all recovered after treatment. The
      diagnosis of primary pyogenic abscess requires a high index of suspicion and the
      best treatment is early operative drainage and administration of systemic
      antibiotics.

PMID- 9549581
TI  - Experimental model of multidirectional disc hernia in rats.
AB  - We have carried out an experimental investigation of lesions of the
      intervertebral disc produced by flexion, lateral bending and rotational forces in
      an attempt to produce disc herniations. Adult Wistar rats were divided into 4
      groups: control and posterior, lateral and rotational herniation. There were 10
      rats in each group. The tail between the 5th and 8th vertebral segments was used.
      A Kirschner wire was inserted into each of 2 adjacent vertebrae and the movement
      produced had an apex which was anterior or lateral depending on the group
      involved. Variables such as rupture of the annulus, the cellularity of the
      nucleus pulposus and the site of the lesion in the disc were studied
      histologically. The height of the disc, the protrusion, the thickness, and the
      surfaces of the annulus fibrosus and the nucleus pulposus were measured. In every
      case we found a nuclear displacement which did not become a protrusion. The
      surface parameters and the cellularity of the nucleus pulposus are most useful
      indicators and should be included in any study examining the disc after the
      injection of substances for treatment.

PMID- 9549582
TI  - Stimulation of bone formation by intraosseous injection of basic fibroblast
      growth factor in ovariectomised rats.
AB  - The effect on intraosseous bone formation of a single local injection of
      recombinant human basic fibroblast growth factor into trabecular bones was
      examined in ovariectomised osteoporotic rats. Fibroblast growth factor (400
      micrograms), or the vehicle alone, was injected into the ilium at 16 weeks after
      ovariectomy or a simulated operation. Bone mineral density in the ovariectomised
      rats increased to a level similar to the latter at 2 weeks and reached a maximum
      at 8 weeks. After 8 weeks, BMD decreased slowly and the value at 24 weeks was
      still higher than that in the ovariectomised rats. Fibroblast growth factor
      stimulated osteoid formation in the first 2 weeks, bone volume reaching a peak at
      8 weeks. From 8 to 12 weeks, bone resorption increased, resulting in decreases in
      bone volume to the levels of the group with simulated operations at 24 weeks.
      Structural analysis at 8 and 24 weeks showed that ovariectomy decreased the
      continuity of trabeculae and the injection of fibroblast growth factor restored
      it to levels higher than, or equal to, those who had the simulated operation. The
      present study demonstrated that intraosseous fibroblast growth factor given to
      ovariectomised rats restored bone volume and quality to the levels of the rats
      who had a simulated operation only.

PMID- 9549584
TI  - The disappearing exostosis? A report of an unusual case.
AB  - A girl aged 11 years was referred to us with a medial upper right tibial
      exostosis. As the lesion was asymptomatic, surgery was not undertaken. The
      patient defaulted from follow up, and, when reviewed 32 months later, there was
      no clinical or radiographic evidence of the exostosis. Spontaneous involution of
      an exostosis may occasionally occur in childhood.

PMID- 9549583
TI  - Isolation and differential secretion of metalloproteinase by superficial
      chondrocytes in articular cartilage.
AB  - Chondrocytes from superficial layers of articular cartilage have distinct
      phenotypic properties which are different from those of cells obtained from the
      deeper areas. We describe a method that isolates highly purified articular
      cartilage chondrocytes from the superficial layers. When the superficial cells
      are stimulated in vitro with a source of cytokines, they secrete greater amounts
      of metalloproteinase compared to chondrocytes obtained from a deeper area.

PMID- 9549585
TI  - Fracture of the upper radius with ipsilateral dislocations of the elbow and
      superior radio-ulnar joints. A case report.
AB  - We report the rare combination of a closed fracture of the upper third of the
      radius with ipsilateral posterior dislocation of the elbow joint and disruption
      of the superior radio-ulnar joint. Although in the Bado classification there is a
      fourth type that describes fractures of both radius and ulna with dislocation of
      the superior radio-ulnar joint, it does not include the injury we report. We
      review of the literature and put forward an extension of Bado's classification so
      that fractures of either, or both, the radius and ulna associated with
      pericubital dislocations will be included.

PMID- 9549586
TI  - Simultaneous anterior dislocation of the shoulder and fracture of the ipsilateral
      humeral shaft. Two case reports.
AB  - Two patients with anterior dislocation of the shoulder and ipsilateral fracture
      of the shaft of the humerus have been studied and the mechanism of their injuries
      has been documented. Closed reduction of the dislocations was performed under
      anaesthesia during surgery for humeral fixation with a dynamic compression plate.
      The fractures and dislocations healed without any problems at 6 to 9 months
      postoperatively. At recent follow-up, one patient had returned to work and
      regained normal mobility. The other patient had the sequelae of a brachial plexus
      injury. The literature on this subject is reviewed.

PMID- 9549587
TI  - Assessment of International Psychogeriatrics: the Journal of the International
      Psychogeriatric Association.
AB  - In 1996, new editorial management took over International Psychogeriatrics (IP),
      only a year after the frequency of its publication increased from semiannual to
      quarterly. At the request of the editorial board, an assessment of the journal
      was conducted by comparing it to other journals in the field of geriatrics and,
      specifically, geriatric psychiatry. The evaluation included both a modified
      citation analysis and a review of journal content. The study was undertaken in
      order to identify the position the journal has within its discipline. Further, it
      was to identify the journal's strengths and weaknesses with the overall goal of
      recommending changes to IP's current content and format. IP ranked seventh of 15
      journals in terms of impact factor. It is primarily oriented towards the
      publication of original research, and features fewer longer articles than others
      in the field. Adding a wider variety of content may increase the overall interest
      in the journal. However, these changes must be weighed against the goals of the
      journal and its reputation as a source of original research in the field of
      geriatrics.

PMID- 9549588
TI  - A detailed phenomenological comparison of complex visual hallucinations in
      dementia with Lewy bodies and Alzheimer's disease.
AB  - Visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB),
      but little is known about their phenomenology. A total of 73 dementia patients
      (42 DLB, 30 Alzheimer's disease [AD], 1 undiagnosed) in contact with clinical
      services were assessed with a detailed standardized inventory. DLB was diagnosed
      according to the criteria of McKeith and colleagues, AD was diagnosed using the
      NINCDS-ADRDA criteria. Autopsy confirmation has been obtained when possible. VH
      were defined using the definition of Burns and colleagues. Detailed descriptions
      of hallucinatory experiences were recorded. Annual follow-up interviews were
      undertaken. The clinical diagnosis has been confirmed in 18 of the 19 cases that
      have come to autopsy. A total of 93% of DLB patients and 27% of AD patients
      experienced VH. DLB patients were significantly more likely to experience
      multiple VH that persisted over follow-up. They were significantly more likely to
      hear their VH speak but there were no significant differences in the other
      phenomenological characteristics including whether the hallucinations moved, the
      time of day that they were experienced, their size, the degree of insight, and
      whether they were complete. VH may be more likely to be multiple, to speak, and
      to be persistent in DLB patients. These characteristics could potentially aid
      accurate diagnosis.

PMID- 9549589
TI  - Can neuroimaging techniques identify individuals at risk of developing
      Alzheimer's disease?
AB  - Recent studies indicate that neuroimaging techniques such as magnetic resonance
      imaging, positron emission tomography, and single-photon emission computed
      tomography can accurately differentiate patients with Alzheimer's disease (AD)
      from elderly controls. This report reviews the results of neuroimaging studies of
      two at-risk populations: subjects with the epsilon 4 allele of the apolipoprotein
      E and those with mild cognitive impairment. The results of the work published to
      date indicate that the presence of the epsilon 4 allele is a risk factor for AD
      and that its predictive validity can be enhanced by neuropsychological and/or
      neuroimaging evaluation. The results also show that patients with mild cognitive
      impairment display a number of structural and functional imaging abnormalities
      that are more pronounced in the temporal and parietal lobes. We suggest that the
      use of neuroimaging techniques can improve the detection of subjects early in the
      course of AD, although the sensitivity and the specificity of this approach still
      await a more detailed prospective evaluation.

PMID- 9549590
TI  - Efficacy of psychosocial treatments for noisemaking in severe dementia.
AB  - Noisemaking is one of the most disturbing behavior disorders associated with
      dementia. Standard management practices, including pharmacological interventions,
      are not very successful in treating the behavior. Very little research has been
      carried out to evaluate innovative treatments or to determine the etiology of
      noisemaking. In this article, we report on a series of 12 case studies in which
      we tested the efficacy of some psychosocial interventions in reducing the
      frequency of noisemaking in long-term-care residents with severe dementia.
      Interventions were contingent reinforcement of quiet behavior and environmental
      stimulation tailored to individual preferences. Of the 12 patients recruited into
      the study, 2 died during the course of observations, 3 were not observed to be as
      noisy as reported by staff, and 3 showed a clear reduction in noise during the
      intervention period. Four patients did not show any overall reduction in
      noisemaking during psychosocial interventions. Future research could
      differentiate between types of interventions in successful cases and attempt to
      control further for the consistent application of interventions by long-term-care
      staff.

PMID- 9549591
TI  - Effect of a program of diverse activities on disturbed behavior in three severely
      demented patients.
AB  - The effects of a daily program of various activities on disturbed behavior were
      studied prospectively in three patients with severe dementia. Prior to the study,
      patients had not responded to treatment with benzodiazepines and/or neuroleptics.
      The study consisted of three periods, each lasting for 4 weeks: i.e., baseline,
      intervention, and follow-up. During each period, behavior was assessed by means
      of observation scales: GIP, SDAS, and CGI. Psychotropic medication was held as
      constant as possible. During intervention, the patients took part in a program of
      activities, including group, musical, physical, and social activities. During
      baseline and follow-up, patients followed the regular ward activities. The
      patients showed different responses, probably related to personal interests.
      Possible implications for the treatment of patients with dementia, complicated by
      disturbed behavior, and suggestions for future research are discussed. The
      enthusiasm of the nursing staff dealing with these patients was a promising
      result.

PMID- 9549592
TI  - Clinical experience with risperidone, haloperidol, and thioridazine for dementia
      associated behavioral disturbances.
AB  - The efficacy and safety of risperidone, haloperidol, and thioridazine for
      treating dementia-associated behavioral disturbances were evaluated in a
      retrospective study of 186 patients aged 65 years or older with DSM-III-R or DSM
      IV diagnoses of Alzheimer's dementia, senile dementia NOS, or organic brain
      syndrome. Study patients were selected from the charts of 12,000 residents of 60
      long-term-care facilities in New Jersey if they were treated with one of the
      three agents for behaviors dangerous to themselves or others. The 186 selected
      patients included 60 treated with risperidone (mean, 1 mg/day), 83 with
      haloperidol (mean, 2 mg/day), and 43 with thioridazine (mean, 33 mg/day). Target
      behaviors were violence (74 patients), shouting (31), delusions (26), paranoia
      (19), pacing (3), and mixed behaviors (33). Target behaviors improved in 94% of
      patients given risperidone, 65% given haloperidol, and 67% given thioridazine (p
      < .001). Treatment failures (treatment discontinued in patients because of side
      effects or no improvement) were more frequent in patients started on haloperidol
      (28) or thioridazine (15) than on risperidone (3). Extrapyramidal symptoms were
      reported in 7% of patients taking risperidone, 22% taking haloperidol, and 18%
      taking thioridazine. Safe, effective doses are readily achieved with risperidone
      but difficult to achieve with haloperidol or thioridazine because their effective
      doses often cause unacceptable side effects. These data are only suggestive
      because no guidelines exist for defining or measuring behavioral disturbances or
      for how they are affected by social, psychological, or environmental factors.

PMID- 9549593
TI  - Temporary institutional respite in dementia cases: who utilizes this form of
      respite care and what effect does it have?
AB  - In the studies on the effects of temporary institutional respite (TIR) published
      to date, a slight reduction of subjective burden has been established. The hope
      that this form of respite care might have a positive effect on the activities of
      daily living or on the health of the care recipients has not yet been confirmed.
      A considerable deficit in the methodology applied might be a reason for this.
      There is no denying the fact that there is a clear need for respite services,
      particularly because every seventh person providing care for a dementia patient
      requiring personal care belongs to a high-risk group that is characterized by
      serious reduction in his or her physical health and psychological well-being. TIR
      is primarily utilized by adult child caregivers (daughters and daughters-in-law)
      affected by high subjective burden who are providing care for dementia patients
      with extensive nursing needs.

PMID- 9549594
TI  - Factor structure of the Dementia Mood Assessment Scale in a cohort of community
      dwelling elderly.
AB  - We examined the factor structure of the 28-item Dementia Mood Assessment Scale
      (DMAS), an instrument to assess depressive symptoms in older adults with
      cognitive impairment, in a cohort of 165 community-dwelling elderly with varying
      degrees of cognitive impairment. Factor analysis using principal components
      analysis and varimax rotation was performed to explore the presence of subscales
      and examine construct validity. A five-factor structure involving all 28 items
      accounting for 63.2% of the variance in the DMAS scores was derived. Factors were
      named: Depressed Affect, Environmental Interaction, Diurnal Patterns,
      Agitation/Suspicion, and Somatic Indicators. This factor structure reflects the
      often differing presentations of depressive symptoms in older adults with varying
      degrees of cognitive function and establishes the construct validity of the DMAS
      in this population. We conclude that the DMAS may be used for differentiated
      clinical assessment of depressive symptoms along major dimensions of depressive
      illness in this cohort of elderly.

PMID- 9549595
TI  - Delusional parasitosis in the elderly: a review and report of six cases from
      northern Finland.
AB  - A patient with delusional parasitosis has a strong conviction of being infested
      with parasites: for example, lice or worms. Such a patient is not satisfied with
      assurances or test results that no parasites are present, but is so convinced
      that he or she will go as far as to bring the parasites in "matchboxes" to a
      physician. Subjectively worried, the patient may try to pick the parasites out of
      the skin, causing cutaneous lesions and even ulcerations. The condition is
      classified as a delusional/paranoid disorder, somatic type according to DSM-III
      R. Not much is known epidemiologically of this rare disorder, which usually
      affects older women who often are isolated socially. Therapy is regarded as
      difficult, and a wide variety of treatment methods have been attempted. In this
      article six female cases are presented, showing that a typical patient is an
      elderly woman who has suffered losses or is socially isolated. These patients
      lack deeper psychiatric insight into their problem, so they are mostly in the
      care of nonpsychiatric physicians. Treatment with a low dose of high-potency
      neuroleptics combined sometimes with antidepressants appears to be effective.
      Reducing social isolation is also important.

PMID- 9549596
TI  - Psychiatric manifestations of normal-pressure hydrocephalus: a short review and
      unusual case.
AB  - Normal-pressure hydrocephalus (NPH) is a common cause of potentially reversible
      dementia. It can present with psychiatric manifestations that may hinder its
      diagnosis. A 68-year-old man presented with a paranoid psychosis and mild
      cognitive impairment, but not neurological signs or classic "triad." Gait
      disturbance and urinary incontinence developed later in the course of illness
      after the diagnosis of NPH had already been made on computed tomographic (CT)
      scanning. A lumbo-peritoneal shunt was performed, followed by full remission of
      psychotic symptoms, as well as considerable improvement in functioning,
      continence, and gait. This case demonstrates the need to consider NPH when older
      patients present with psychotic symptoms, particularly in the presence of
      cognitive impairment, gait disturbance, or incontinence. The decision whether to
      perform a shunting operation is often difficult, because selection of patients
      with good prognosis is still inaccurate. CT scanning of the brain is an important
      investigation in older patients presenting with both functional and organic
      disorders.

PMID- 9549597
TI  - The relationship between two scales measuring aggressive behavior among
      continuing-care psychogeriatric inpatients.
AB  - Aggressive behavior among the elderly is a neglected area of research. An 18-week
      prospective study of aggressive behavior on a continuing-care psychogeriatric
      ward provided data to examine the relationship between two aggression scales
      (SOAS and RAGE). There was a strong and significant correlation between the SOAS
      and RAGE scales for the total and the subscale scores. Both these scales appear
      useful in measuring aggressive behavior among continuing-care psychogeriatric
      inpatients. Also, the nursing staff can be trained to complete these scales
      effectively.

PMID- 9549598
TI  - Smoking and illicit drug use--a lesson yet to be learned.

PMID- 9549599
TI  - Tobacco smoking and nicotine dependence: biological basis for pharmacotherapy
      from nicotine to treatments that prevent relapse.

PMID- 9549600
TI  - Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO
      B) inhibition.
AB  - We measured the concentration of brain monoamine oxidase B (MAO B; EC 1.4.3.4) in
      8 smokers and compared it with that in 8 non-smokers and in 4 former smokers
      using positron emission tomography (PET) and deuterium substituted [11C]L
      deprenyl ([11C]L-deprenyl-D2) as a radiotracer for MAO B. Smokers had
      significantly lower brain MAO B than non-smokers as measured by the model term
      lambda k3 which is a function of MAO B activity. Reductions were observed in all
      brain regions. Low brain MAO B in the cigarette smoker appears to be a
      pharmacological rather than a genetic effect since former smokers did not differ
      from non-smokers. Brain MAO B inhibition by cigarette smoke is of relevance in
      light of the inverse association between smoking and Parkinson's disease and a
      high prevalence of smoking in psychiatric disorders and in substance abuse.
      Though nicotine is at the core of the neuropharmacological actions of tobacco
      smoke, MAO B inhibition may also be an important variable in understanding and
      treating tobacco smoke addiction.

PMID- 9549601
TI  - Cigarette smoking and major depression.
AB  - The authors review recent literature that has demonstrated an association between
      cigarette smoking behavior and major depression. Persons with major depression
      are more likely to smoke and to have difficulty when they try to stop. When they
      manage to succeed in stopping, such persons are at increased risk of experiencing
      mild to severe states of depression, including full blown major depression. The
      period of vulnerability to a new depressive episode appears to vary from a few
      weeks to several months after cessation. This knowledge suggests a relationship
      between smoking and depression that is complex, pernicious, and potentially life
      long. It is recommended that cessation treatments incorporate screening
      procedures that will identify those patients with a propensity to depression and
      monitor the emergence of postcessation depression, particularly in those with a
      history of depression.

PMID- 9549602
TI  - Caffeine and nicotine use in an addicted population.
AB  - This study was undertaken to examine differences in caffeine and nicotine use
      between the psychiatric population and the addicted population in a private
      psychiatric inpatient facility. Eighty-six patients on an adult addictive disease
      inpatient unit and 80 patients on an adult psychiatry unit in a private
      psychiatric hospital were interviewed with regard to their use of nicotine and
      caffeine. In addition, demographic information and primary diagnoses were
      obtained from the psychiatric admission assessment in the medical record as
      listed by the admitting psychiatrist. Although there was little difference in
      psychiatric patients vs. chemically dependent patients with regard to the
      percentage of caffeine users, the chemically dependent individuals drank more
      coffee, soft drinks, and tea. A much greater percentage of the chemically
      dependent individuals also smoked cigarettes, although not in a greater amount
      than the psychiatric patients who smoked. Because group assignment was not
      random, ordinary least squares (OLS) regression analyses were conducted to
      determine the independent associations of age, sex, education, and treatment
      population in predicting levels of caffeine and tobacco use. Even after
      controlling for demographic differences between the two samples, chemically
      dependent patients still reported higher levels of daily caffeine and tobacco use
      than patients on the general psychiatric unit.

PMID- 9549603
TI  - Comorbid cigarette and alcohol addiction: epidemiology and treatment.
AB  - The close association of nicotine addiction and alcoholism is well established.
      As many as 80% of alcoholics smoke, and 30% of smokers are alcoholics. The
      mortality from cigarette smoking and alcoholism individually is very high, as an
      estimated 400,000 deaths from tobacco and 100,000 deaths from alcoholism are
      reported annually. Cigarettes and alcohol interact to cause certain cancers,
      e.g., head and neck. Only recently has attention been focused on the role of
      tobacco in abstinent alcoholics. An important study found high rates of mortality
      from tobacco in abstinent alcoholics in recovery. However, the mortality rates
      from alcoholism were high and predominant. Of great importance is that studies
      show that abstinence from alcohol essentially eliminates the premature deaths or
      increased mortality rates from active alcoholism. Similar studies showing a
      reduction in mortality from abstinence in nicotine addiction have not been
      forthcoming. The importance of treating nicotine addiction, however, is clear to
      reduce the high mortality rates from tobacco smoking in active or abstinent
      alcoholics.

PMID- 9549604
TI  - Tobacco, alcohol, and drug use in a primary care sample: 90-day prevalence and
      associated factors.
AB  - BACKGROUND: Primary care settings are an ideal system in which to identify and
      treat substance use disorders. OBJECTIVE: To ascertain the prevalence of tobacco,
      alcohol, and drug use in the office of 88 primary care clinicians by gender, age
      and ethnicity. METHOD: 21,282 adults ages 18-65 completed a self-administered
      Health Screening Survey while participating in a trial for early alcohol
      treatment. RESULTS: The period prevalence of tobacco use was 27%. For alcohol:
      abstainers 40%, low risk drinkers 38%, at-risk drinkers 9%, problem drinkers 8%,
      and dependent drinkers 5%. Twenty percent of the sample reported using illicit
      drugs five or more times in their lifetime and 5% reported current illicit drug
      use. There were marked differences in alcohol use disorders by age and ethnicity.
      The majority of persons who smoked reported the desire to cut down or stop using
      tobacco. SIGNIFICANCE: This is the first report on the combined prevalence of
      tobacco, alcohol and drug disorders in a large sample of persons attending
      community-based non-academic primary care clinics. This report confirms the high
      prevalence of these problems and suggests that patients will accurately complete
      a self-administered screening test such as the Health Screening Survey. The
      office procedures developed for this study provide Managed Care Organizations
      with a system of care that can be used to screen all persons for tobacco, alcohol
      and drug use disorders.

PMID- 9549605
TI  - Incorporating nicotine dependence into addiction treatment.
AB  - An addiction treatment program devoted two years to preparing to become a
      smokefree treatment unit that addressed nicotine dependence as another drug
      dependency. Data collected from September 1990 to July 1995 on 263 admissions
      before becoming smokefree and 2182 admissions after making the transition
      revealed that going smokefree did not affect the incidence of premature
      discharges or aggressive behavior, and did not change the overall rate of program
      completion by either smokers or nonsmokers. During the first three months after
      going smokefree, the program completion rate dropped for both smokers and
      nonsmokers; by the fourth month, it had returned to previous levels. Seventeen
      months after going smokefree, the program completion rate was higher than it had
      ever been. This suggests that the drop in the program completion rate was due to
      the disruption caused by a significant programmatic change and not due to the
      unit's smokefree status, and that the increasing experience of staff in treating
      nicotine dependence resulted in improved patient outcomes.

PMID- 9549606
TI  - Social anxiety and history of behavioral inhibition in young adults.
AB  - To evaluate the relationship between the childhood temperament behavioral
      inhibition (BI) and anxiety symptomology, we investigated differences in
      retrospective reports of childhood BI among undergraduates reporting one of the
      following: (a) Social anxiety (n = 10), (b) generalized anxiety (n = 13), (c)
      both social and generalized anxiety (n = 15), and (d) minimal social and
      generalized anxiety (n = 38). Contrary to the hypothesis that BI acts as a
      nonspecific risk factor for anxiety symptoms, our findings revealed that a
      history of childhood BI was associated with symptoms of social phobia but not
      generalized anxiety disorder. Moreover, participants displaying symptoms of both
      generalized anxiety disorder and social phobia were no more likely to show a
      childhood history of BI than participants displaying social phobia symptoms
      alone. These data suggest that a childhood history of BI may be more strongly
      associated with adult social anxiety than some other types of anxiety pathology.

PMID- 9549607
TI  - Posttraumatic stress disorder and comorbid major depression: is the correlation
      an illusion?
AB  - We have examined data from 107 motor-vehicle accident (MVA) victims with regard
      to whether the presence of comorbid depression is important clinically, and with
      regard to whether the threshold for diagnosing the comorbid depression should be
      raised because of symptom overlap between posttraumatic stress disorder (PTSD)
      and major depression. Of the 62 MVA victims who met the criteria for PTSD 1 to 4
      months post-MVA, 33 also met the criteria for major depression, with 27 cases for
      which the depression occurred post-MVA. A LISREL 8.12a analysis indicates that
      PTSD and major depression are correlated, but independent, responses to trauma.
      Those with PTSD and depression are more subjectively distressed, suffer more
      major role impairment, and remit less readily over the first 6 months of
      prospective follow-up than those with PTSD alone. The threshold for diagnosing
      comorbid depression (5 or 6 depressive symptoms versus 7 to 9 depressive
      symptoms) has no important effects on any of the indicators of "caseness."

PMID- 9549608
TI  - Don't worry and beware of white bears: thought suppression in anxiety patients.
AB  - The ability to suppress unwanted thoughts was investigated in patients with
      Generalized Anxiety Disorder (GAD; n = 29), Speech Phobics (n = 25), and
      nonanxious controls (n = 28). All participants spent 5 minutes thinking aloud
      about anything that came to mind while trying not to think of white bears. In
      another task, they thought aloud for 5 minutes while trying not to think of their
      main worry. Intrusions of unwanted thoughts were signaled by button presses and
      recorded on tape. In accordance with the disorder's definition and complaints of
      the GAD patients, they showed more intrusions of their main worry than of white
      bears. The opposite was true for other participants. Compared to a baseline
      measure, all participant groups were unable to reduce duration of main worry
      thoughts when trying to suppress them.

PMID- 9549609
TI  - Posttraumatic stress disorder and work-related injury.
AB  - The literature indicates a substantial overlap between chronic pain and
      posttraumatic stress disorder (PTSD) symptoms in individuals who sustain
      accidental injury. To date, however, there have been no studies of PTSD symptoms
      in individuals who experience work-related injury. Consequently, we assessed 139
      consecutive injured workers using the Modified PTSD Symptom Scale (Falsetti,
      Resnick, & Kirkpatrick, 1993), as well as a number of general measures of
      psychopathology. Most participants reported chronic pain and all were receiving
      workers compensation. Results indicated that 34.7% and 18.2% of the sample
      reported symptoms consistent with PTSD and partial PTSD, respectively. When PTSD
      symptom frequency and severity were considered criterion variables in multiple
      regression analyses, depression was found to be significantly associated with the
      former and anxiety sensitivity, social fears, and somatic focus with the later.
      Finally, these measures of general psychopathology correctly classified 78.6% of
      individuals with PTSD and 81.3% of those with no PTSD. These results suggest that
      a considerable proportion of injured workers display symptoms consistent with
      PTSD and that these symptoms are related to general negative affect.
      Implications, including the suggestion of clinical intake screening of PTSD in
      this population, are discussed.

PMID- 9549610
TI  - Deja vu all over again: critical misunderstandings concerning anxiety sensitivity
      and constructive suggestions for future research.
AB  - The debate concerning the relation between anxiety sensitivity (AS) and trait
      anxiety has been constructive for the field and has suggested a number of
      important directions for future research. Reiss' (1997) commentary on AS and
      trait anxiety in this journal, however, contains several serious factual mis
      statements and logical errors that confuse, rather than clarify, many of the
      central issues in this debate. These misunderstandings are corrected and the
      implications of the issues raised by Reiss are addressed here. The authors
      suggest that future research on AS (a) embed this construct within the context of
      broader temperamental and personality variables and (b) explicitly recognize the
      biodirectionality of emotional and cognitive influences.

PMID- 9549611
TI  - Bone cell behavior on Matrigel-coated Ca/P coatings of varying crystallinities.
AB  - Rat calvarial cell mitogenic behavior was investigated on various biomaterials
      coated with Matrigel, a basement membrane matrix containing growth factors. Low
      (20-40%) and high (70-90%) crystallinity hydroxyapatite (rHA and cHA), rough
      titanium (Ti), and tissue culture polystyrene (TP) surfaces were compared.
      Surface chemistry and calcium resorption of HA coatings, alkaline phosphatase
      activity (APA), and growth of cells were measured for Matrigel-coated and
      uncoated surfaces at 2, 7, and 14 days. Gene expression for four noncollagenous
      bone-related proteins (osteonectin, osteopontin, alkaline phosphatase, and
      osteocalcin) was also investigated by reverse transcription and polymerase chain
      reaction up to 28 days. Ca concentration in incubating solutions increased with
      time for the two types of HA coatings and was always greater for rHA than cHA.
      Surface chemistry and coating dissolution rates were not affected by the presence
      of Matrigel or cells throughout the study. APA of cells on the two HA-coated
      surfaces was comparably enhanced in the presence of Matrigel and was greater than
      on Ti surfaces. Only HA surfaces showed an increased APA of cells with time in
      the presence of Matrigel. Cell growth peaked at 7 days and was greatest for cells
      on the two HA surfaces and without Matrigel. At 14 days, cell growth was
      comparable on the four surfaces. The presence of HA and Matrigel enhanced cell
      specific APA at 14 days. Gene expression for all four proteins investigated
      showed no differences between surfaces after 7 days. At 2 and 7 days, gene
      expression was indicative of proliferation for Ti, and of proliferation,
      differentiation, and mineralization for HA and TP more so without Matrigel. The
      addition of this matrix significantly enhanced mitogenicity of calvarial cells on
      HA only after 14 days. Matrigel eliminated differences seen between the two HA
      coatings. Gene expression was not enhanced or inhibited by the presence of
      Matrigel.

PMID- 9549612
TI  - Platelet adhesion onto chargeable functional group gradient surfaces.
AB  - Functional group gradients were prepared on low-density polyethylene (PE) sheets.
      The surface density of grafted functional groups was gradually changed along the
      sample length by way of corona discharge treatment with gradually increasing
      power following graft copolymerization of acrylic acid (AA), sodium p-styrene
      sulfonate (NaSS), or N,N-dimethyl aminopropyl acrylamide (DMAPAA). AA and NaSS
      are negatively chargeable and DMAPAA is positively chargeable in phosphate
      buffered saline or plasma solution at pH 7.3-7.4. The prepared functional group
      gradient surfaces were characterized by measurement of the water contact angle,
      by electron spectroscopy for chemical analysis, and by Fourier transform infrared
      spectroscopy in the attenuated total reflectance mode. All these measurements
      indicated that the functional groups were grafted onto the PE surfaces with
      gradually increasing density. The platelets adhered to the functional group
      gradient surfaces along the sample length were counted and observed by scanning
      electron microscopy. It was observed that the platelet adhesion to the gradient
      surfaces decreased gradually with the increasing surface density of functional
      groups. This may be related to the hydrophilicity of the surfaces. The DMAPAA
      grafted surface showed a large amount of platelet adhesion, probably due to its
      positive charge character, while the AA-grafted surface, which is charged
      negatively, showed poor platelet adhesion. However, the NaSS-grafted surface,
      which is also charged negatively, showed a relatively large amount of platelet
      adhesion. This may be associated with the existence of an aromatic ring close to
      the ionizable group in NaSS. It seems that surface functional groups and their
      charge character, as well as wettability, play important roles for platelet
      adhesion.

PMID- 9549613
TI  - In vitro engineering of human skin-like tissue.
AB  - Coverage of large, full-thickness burns presents a challenge for the surgeon due
      to the lack of availability of the patient's own skin. Currently, tissue
      engineering offers the possibility of performing a suitable therapeutic wound
      coverage after early burn excision by using cultured keratinocyte sheets
      supported by a dermal layer. The aim of this study was to develop and
      characterize a skin substitute composed of both epidermal and dermal elements.
      For this purpose we grew keratinocytes and fibroblasts separately for 15 days
      within two different types of biomaterials. Cells then were co-cultured for an
      additional period of 15 days, after which samples were taken and processed with
      either classic or immunohistochemical stainings. Results showed that (1) human
      fibroblasts and keratinocytes can be cultured on hyaluronic acid-derived
      biomaterials and that (2) the pattern of expression of particular dermal
      epidermal molecules is similar to that found in normal skin. The data from this
      study suggest that our skin equivalent might be useful in the treatment of both
      burns and chronic wounds.

PMID- 9549614
TI  - Adsorption of proteins onto poly(ether urethane) with a phosphorylcholine moiety
      and influence of preadsorbed phospholipid.
AB  - In a previous report we demonstrated that the blood compatibility of poly(ether
      urethane) (PEU) was improved by grafting phosphorylcholine (PC) groups on the
      surface. The improved blood compatibility was indicated by decreased platelet
      adsorption/activation and reduced thrombin formation at the polymer surface in
      experiments in which the surfaces were contacted with platelet-rich plasma in
      vitro. In the present study, we investigated the effect of grafted PC groups at a
      PEU surface on protein and phospholipid adsorption. Adsorption of human
      fibrinogen (Fg), human serum albumin (Alb), human high-molecular-weight kininogen
      (HMWK), and dioleoyl phosphatidylcholine (DOPC) vesicles was measured by
      ellipsometry. For this purpose, thin PEU films were cast on silicon wafers. The
      polymer film was photochemically modified with a PC-containing aryl azide. The
      presence of PC groups on the polymer surface was demonstrated by ESCA (Electron
      Spectroscopy for Chemical Analysis). The hydrophilicity of the polymer surface
      increased by the surface modification, as indicated by a decrease of the contact
      angle from 59 degrees before to 43 degrees after modification. Our data show that
      the presence of PC groups has little effect on the adsorption of proteins to a
      PEU surface. The highest adsorption was observed for Fg (0.49 microgram/cm2 on PC
      modified PEU and 0.50 microgram/cm2 on PEU), followed by HMWK (0.28 microgram/cm2
      on both PC-modified PEU and PEU), and Alb (0.16 microgram/cm2 on PC-modified PEU
      and 0.18 microgram/cm2 on PEU). Protein adsorption was further studied on a
      "biomembrane-like" DOPC bilayer formed on hydrophilic silicon. We found no
      protein adsorption on this DOPC bilayer. The adsorption of small unilamellar DOPC
      vesicles on the polymer surfaces amounted to about 0.06 microgram/cm2
      (corresponding to circa 30% of monolayer coverage) and was similar for PC
      modified PEU and PEU. Despite this partial surface coverage, preadsorbed DOPC on
      the polymer surface diminished the subsequent adsorption of proteins
      considerably. These results show that the mere presence of phosphorylcholine
      groups on a PEU surface is insufficient to suppress protein adsorption. The
      highly ordered structure of natural phospholipid bilayers seems to be required to
      suppress protein adsorption effectively.

PMID- 9549615
TI  - Release of bioactive human growth hormone from a biodegradable material:
      poly(epsilon-caprolactone).
AB  - We have characterized the biodegradable material poly(epsilon-caprolactone) (PCL)
      as a delivery system for recombinant human growth hormone (hGH). Two contrasting
      methods for the manufacture of the biomaterial were investigated: namely, solvent
      casting and solvent casting particulate leaching; the latter yielded porous PCL
      discs. The degree of porosity, which was assessed by scanning electron
      microscopy, could be controlled by incorporating selected concentrations of
      particulate sodium chloride during the manufacturing process. Bioactive hGH
      released from the PCL preparations was quantified with a highly sensitive and
      precise bioassay which was based upon hGH activation of rat lymphoma Nb2 cells.
      Eluates obtained from control discs of PCL which had not been loaded with hGH
      proved to be nontoxic when tested on these cells. The release of bioactive hGH
      from hormone-loaded nonporous discs of PCL was found to be a direct function of
      the initial hormone loading dose. Increased porosity of the discs manufactured by
      solvent casting particulate leaching increased the delivery of hGH from discs
      which had been immersion loaded. However, hGH release after surface loading was
      independent of porosity. Hormone concentrations were also assessed by immunoassay
      so that the ratios of bio- to immunoactivity (B:I ratio) of the hormone release
      could be determined. We found that the B:I ratio of the hormone after release
      from unstored discs was identical to that of the hormone prior to its
      incorporation into the PCL, demonstrating that the mild incorporation procedures
      utilized had not adversely affected the structural integrity of the hormone.
      However, if the hormone-loaded discs were stored at 37 degrees C prior to
      elution, the B:I ratios of the hGH released decreased indicating that this
      compromised the bioactive site.

PMID- 9549616
TI  - Study of creep behavior of ultra-high-molecular-weight polyethylene systems.
AB  - The short- and long-term creep behaviors of ultra-high-molecular-weight
      polyethylene (UHMWPE) systems (compression-molded UHMWPE sheets and self
      reinforced UHMWPE composites) have been investigated. The short-term (30-120 min)
      creep experiment was conducted at a load of 1 MPa and a temperature range of 37
      62 degrees C. Based on short-term creep data, the long-term creep behavior of
      UHMWPE systems at 1 MPa and 37 degrees C was predicted using time-temperature
      superposition and analytical formulas. Compared to actual long-term creep
      experiments of up to 110 days, the predicted creep values were found to well
      describe the creep properties of the materials. The creep behaviors of the UHMWPE
      systems were then evaluated for a creep time of longer than 10 years, and it was
      found that most creep deformation occurs in the early periods. The shift factors
      associated with time-temperature superposition were found to increase with
      increasing temperature, as per the Arrhenius equation. The effects of
      temperature, materials, and load on the shift factors could be explained by the
      classical free volume theory.

PMID- 9549617
TI  - Effects of curing time and filler concentration on curing and postcuring of
      urethane dimethacrylate composites: a microcalorimetric study.
AB  - The isothermal enthalpy changes with time of a dental composite were examined by
      microcalorimetry to isolate the effects of different filler concentrations and
      curing times on chemical aging of these composites. Urethane dimethacrylate
      (UDMA) monomer, zirconia-silica (ZS) powder, and 3
      methacryloxypropyltrimethoxysilane (MAPM) were used as organic and inorganic
      matrices, and a coupling agent, respectively. The composite was mixed in
      different ratios and cured by visible light. The enthalpy changes with time for
      0, 15, 45, 75% ZS-filled UDMA and 75% MAPM-silanated ZS-filled UDMA cured for 13,
      30, 90, 150, and 300 s were measured at 37.0 degrees, 57.0 degrees, and 65.5
      degrees C until equilibrium. Increased curing time and filler concentration
      caused the excess enthalpy changes (dH) and their rate of change (dH/dt) to
      increase with annealing time and apparent equilibrium was reached faster. In
      addition, dH showed nonlinear dependence with the increase in filler
      concentration by showing a maxima for samples containing 25 wt% filler. Further,
      filler silanation caused dH/dt to increase and required shorter times to reach
      apparent equilibrium. dH also reached a minimum when samples contained silanated
      filler, compared to composites containing unsilanated filler. It was concluded
      that the shorter curing time caused the occurrence of spontaneous densification,
      which facilitated continual resin curing; and longer curing time caused higher
      crosslinking of the organic phase. Moderate concentration of inorganic phase
      restricts the molecular motion of the surface layer of polymer onto filler
      particles, and the polymer is regarded as highly crosslinked, while a higher
      filler concentration forms aggregates that are covered by the polymer which
      causes a decrease in the molecular packing of the resin, and is reflected as low
      enthalpy values. Finally, silanation of the filler showed a highly endothermic
      reaction that is probably due to breaking and forming of bonds at the interface
      between the organic and the inorganic phases in the composites.

PMID- 9549618
TI  - Step-polarization impedance spectroscopy of implant alloys in physiologic
      solutions.
AB  - A novel test method is presented whereby the polarization behavior and impedance
      characteristics of an electrochemical interface can be determined simultaneously
      from potential-step current transient responses. In this test, small incremental
      steps in potential are applied to an electrochemical interface and the current
      transient response is collected digitally. Then, the data are subjected to a
      numerical Laplace transform technique to obtain the frequency-dependent
      admittance (reciprocal impedance) of the interface. From this analysis, several
      interesting and relevant parameters, including the high- and low-frequency
      resistances, interfacial capacitance, and polarization behavior, can be obtained.
      The mathematical basis for this technique is presented and the methodology is
      applied to three implant alloys (titanium, Co-Cr-Mo, and platinum).
      Electrochemical tests were performed in 0.9% NaCl at room temperature. Starting
      at an initial negative potential, the samples were stepped in 50-mV increments
      every 10 or 100 s up to a maximum potential and then reversed back to the
      starting potential. The impedances were calculated and used to evaluate the
      behavior. From these tests, one can determine the potential dependence of the
      oxide film thickness as well as the changes in the underlying electrochemical
      state of the interfaces with potential. This technique is inexpensive and easily
      applied to any electrochemical system, and yields significantly more
      electrochemical information than either anodic polarization or electrochemical
      impedance spectroscopy alone.

PMID- 9549619
TI  - Variation of oxide films on titanium induced by osteoblast-like cell culture and
      the influence of an H2O2 pretreatment.
AB  - Variations of titanium oxide films induced by osteoblast-like cells in a rat
      calvaria culture system and the influence of an H2O2 pretreatment have been
      investigated by using X-ray photoelectron spectroscopy and electrochemical
      impedance spectroscopy. For abraded titanium, the results revealed that phosphate
      and calcium ions may incorporate into the surface oxide film during the cell
      culture, forming a precipitate with a Ca/P ratio near that of hydroxyapatite.
      Oxidized carbon also was found in the surface layer, most likely precipitated
      hydroxylcarbonated apatite (HCA). The H2O2 pretreatment of titanium in a
      phosphate-buffered saline solution results in a 10-fold thickened porous oxide
      film and large amounts of surface hydroxyl groups as well as a certain amount of
      phosphate ions inside the oxide film. During the cell culture, the H2O2-treated
      titanium surface favors the ion incorporation and precipitation of the HCA-like
      compound, which probably is inlaid into the oxide film. Osteoblast-like cells on
      the H2O2-treated titanium showed a more active morphology during the initial
      stage compared with cells on abraded titanium. Moreover, bone-like nodule
      formation and mineralization appear to be related to the precipitation of the HCA
      like compound on the surface. The results are discussed with respect to corrosion
      resistance, ion incorporation and precipitation of the HCA-like compound on the
      surface, osseointegration, and bioactivity of titanium implants.

PMID- 9549620
TI  - Covalent bonding of PMMA, PBMA, and poly(HEMA)to hydroxyapatite particles.
AB  - In our earlier study, we showed that the surface hydroxyl groups of
      hydroxyapatite have the ability to react with organic isocyanate groups. In this
      study, the feasibility of grafting poly(methyl methacrylate) (PMMA), poly(n-butyl
      methacrylate) (PBMA), and Poly(hydroxyethyl methacrylate) [poly(HEMA)] by using
      the reaction of isocyanate groups with the hydroxyl groups on the surface of HA
      was investigated. Double bonds were introduced to the surface of HA via the
      coupling reaction of isocyanateoethyl methacrylate (ICEM) with HA, or through
      hexamethylene diisocyanate (HMDI) with hydroxyethyl methacrylate (HEMA) and HA,
      followed by radical polymerization in MMA, BMA, or HEMA. Infrared spectra
      indicated the existence of polymers on the surfaces of HA. Thermogravimetric
      analysis also confirmed the presence of grafted polymers on the surface of HA
      powder particles (20-26 wt%). The polymers gave typical PMMA, PBMA, or poly(HEMA)
      infrared spectra, with the exception of amide bands, a result of the coupling
      reaction of ICEM or HMDI with hydroxy groups of HA or HEMA. Therefore it is
      concluded that the polymers were chemically bonded to the surface of HA through
      the isocyanate groups of ICEM or HMDI.

PMID- 9549621
TI  - Bioactive surface coatings for nanoscale instruments: effects on CNS neurons.
AB  - A method is described for depositing onto medical instruments highly
      biocompatible and bioactive surface coatings that can promote and stabilize cell
      attachment. The coatings were made by first depositing thin films of materials,
      such as diamond-like carbon, or metals, including tantalum, tungsten, platinum,
      gold, iridium, palladium, and brass. These surfaces were further altered to
      either promote or inhibit cell growth and spreading by an additional overcoat of
      biological materials, including the extracellular matrix proteins, laminin,
      fibronectin, and collagen IV. The deposition technique used a metal or carbon
      plasma, and the important properties of film adhesion, hardness, density, and
      smoothness are tailored by control of the ion bombardment energy. The films are
      translucent enough to permit high resolution light microscopy for rapid and
      detailed examination of tissue response. These bioactive substrates have been
      tested on primary central nervous system neurons, and the growth response is
      excellent. Equally successful have been our attempts to anchor neurons, without
      associated proliferation of non-neuronal cells, using coatings of poly-d-lysine.
      The method and the materials could have important ramifications in a number of
      areas of research and biotechnology, for example for chronic implantation of
      microelectrode arrays in the cerebral cortex for neuroprosthetic and neural
      monitoring application and for research on the human central nervous system.
      Possible application in nonneuronal fields, such as for coronary artery stents
      and pacemaker electrodes, also are discussed.

PMID- 9549622
TI  - Fluorescent and radiolabeling of polysaccharides: binding and internalization
      experiments on vascular cells.
AB  - Glycosaminoglycans (GAGs) such as heparan sulfates are complex carbohydrate
      polymers. These structural components of the extracellular matrix are essential
      for the adhesion, migration, and regulation of cellular growth. To understand the
      physiological role of GAGs and GAG analogues, a practical approach consists of
      labeling and detecting them in cell extracts, or analyzing binding domains and
      their distributions into the cells. We propose a convenient and reliable method
      for preparing and labeling amino-enriched, polysaccharides with the fluorescent
      derivative 5-[(4,6-dichlorotriazine-2-yl)amino]-fluorescein (DTAF).
      Radioiodination is then performed on the DTAF moiety. This method was applied to
      polysaccharides known to inhibit vascular smooth-muscle cell (SMC) proliferation
      such as functionalized dextrans derived from poly(alpha 1-6 glucose) and fucan,
      poly(L-fucose 4-sulfate) extracted from brown seaweed. Using autoradiography and
      confocal microscopy, we observed the fixation and internalization of labeled
      antiproliferative products in SMCs from rat aorta. These probes can be useful for
      the understanding of polysaccharide-cell interactions. In addition, the method
      presented here can be applied to various synthetic or natural biomedical
      materials.

PMID- 9549623
TI  - An in vitro system for studying osteointegration of dental implants utilizing
      cells grown on dense hydroxyapatite disks.
AB  - A proposed in vitro system is described where chick osteoblasts are cultured on
      the flat surfaces of dense, nonporous HA disks to facilitate the study of bone
      formation at the cell-HA interface. During early bone formation cell-coated HA
      disks were retrieved, fixed with buffered 2% glutaraldehyde, and embedded in
      epon/araldite. The underlying HA disks were demineralized in diluted acid, and
      the intact cell-HA interfaces were re-embedded and thin sectioned for routine
      transmission electron microscopy. Morphologic studies indicated that osteoblasts
      proliferated and formed nodules of cells on the surfaces of HA disks. With
      increasing time in culture, they deposited orthogonally packed collagen fibrils
      between the cell layers that were enveloped by electron-dense mineralized
      globules. Eventually, small spicules of mineralized HA formed along collagen
      fibrils. An electron-dense layer about 50 nm thick was observed on the surface of
      the HA disks. Biochemical studies indicated that cell proliferation, as judged by
      3H-thymidine uptake, increased rapidly during the first 3 days, reached a maximum
      around 6 days, and then declined by 12 days in culture. AP activity and collagen
      synthesis, as determined by 3H-hydroxyproline formation, increased as cellular
      proliferation declined. Mineralization, as judged by 45Ca uptake and spicule
      formation, occurred, as expected, following the increase in AP activity and
      deposition of densely packed collagen fibrils. Thus, all morphological and
      biochemical parameters studied indicate that the proposed in vitro system is
      reproducible and can facilitate the study of the osteointegration of HA-coated
      implants.

PMID- 9549624
TI  - Orientation of ECM protein deposition, fibroblast cytoskeleton, and attachment
      complex components on silicone microgrooved surfaces.
AB  - The microfilaments and vinculin-containing attachment complexes of rat dermal
      fibroblasts (RDF) incubated on microtextured surfaces were investigated with
      confocal laser scanning microscopy (CLSM) and digital image analysis (DIA). In
      addition, depositions of bovine and endogenous fibronectin and vitronectin were
      studied. Smooth and microtextured silicone substrata were produced that possessed
      parallel surface grooves with a groove and ridge width of 2.0, 5.0, and 10.0
      microns. The groove depth was approximately 0.5 micron. CLSM and DIA make it
      possible to visualize and analyze intracellular and extracellular proteins and
      the underlying surface simultaneously. It was observed that the microfilaments
      and vinculin aggregates of the RDFs on the 2.0 microns grooved substrata were
      oriented along the surface grooves after 1, 3, 5, and 7 days of incubation while
      these proteins were significantly less oriented on the 5.0 and 10.0 microns
      grooved surfaces. Vinculin was located mainly on the surface ridges on all
      textured surfaces. In contrast, bovine and endogenous fibronectin and vitronectin
      were oriented along the surface grooves on all textured surfaces. These proteins
      did not seem to be hindered by the surface grooves since many groove-spanning
      filaments were found on all the microgrooved surfaces. In conclusion, it can be
      said that microtextured surfaces influence the orientation of intracellular and
      extracellular proteins. Although results corroborate three earlier published
      hypotheses, they do not justify a specific choice of any one of these hypotheses.

PMID- 9549625
TI  - Biocompatibility analysis of different biomaterials in human bone marrow cell
      cultures.
AB  - A cell culture system for biocompatibility testing of hip implant materials is
      described. Human bone marrow cells have been chosen because these cells are in
      direct contact with the biomaterial after implantation in situ. The sensitivity
      of this method is evaluated for materials which are already being used as
      implants in humans and animal, e.g., hydroxyapatite (HA) ceramic, pure titanium,
      and ultra-high-molecular-weight polyethylene (UHMWPE). As indicative parameters
      of biocompatibility primary cell adherence, cell number, cell proliferation,
      production of extracellular matrix, cell vitality, and cell differentiation are
      described. After 2 weeks in culture, obvious differences between the biomaterials
      with respect to the indicative parameters could be observed. Cell numbers were
      greatest on the HA specimens. In the case of titanium alloys, we observed a
      decreased number of cells. The production of extracellular matrix was high for
      the HA ceramics but reduced for titanium specimens. The polymers allowed only a
      few adherent cells and showed no signs of extracellular matrix production. The
      results can be correlated astonishingly well to animal experiments and clinical
      experiences. Therefore, we suggest that this cell culture system seems to be a
      useful tool for biocompatibility testing of bone implantation materials. It also
      helps reduce animal experiments. With the help of flow cytophotometry, we
      analyzed the influence of biomaterials on large numbers of cells with respect to
      differentiation. There were similar populations of T cells and monocytes on all
      specimens tested. Extended B-cell and granulocyte populations, however, were
      observed with titanium and UHMWPE. Most osteocalcin-containing cells adhered to
      the HA ceramics.

PMID- 9549626
TI  - Histochemical and morphometric observations on the new tissue formed around
      mammary expanders coated with pyrolytic carbon.
AB  - The authors investigated tissue reaction around implanted silicone expanders,
      focusing on clinical morphological and morphometrical aspects. For use in breast
      reconstruction in post mastectomy patients, the surface of a medical-grade
      silicone elastomer was modified, without changing its bulk properties, by the
      addition of a pyrolytic carbon film. The presence of lipophagy, the number of
      foreign-body giant cells of histiocytic origin, and the number of MIB-1 positive
      nuclei (an index of proliferation for the reactive stromal population) were all
      seen to be influenced by the pyrolytic carbon coating. Indeed, all these
      parameters were lower in the membrane formed around Carbofilm TM-coated
      expanders, thus demonstrating the effective protective properties of pyrolytic
      carbon coating.

PMID- 9549627
TI  - Platelet adhesion onto segmented polyurethane surfaces modified by PEO- and
      sulfonated PEO-containing block copolymer additives.
AB  - Polyethylene oxide (PEO) surfaces were prepared by the addition of PEO- and
      sulfonated PEO-containing amphiphilic block copolymers as surface-modifying
      additives in a segmented polyurethane (PU). PEO-PPO-PEO triblock copolymers
      (Pluronics) with different PEO chain lengths (from 2 to 80) were used as
      additives. The prepared film surfaces were characterized by the measurement of
      dynamic water contact angles and electron spectroscopy for chemical analysis. It
      was observed that the PU films containing 10 wt% of PEO additives were surface
      saturated with the additives regardless of their PEO chain length, but the PEO
      chains were more projected from the film surfaces containing the additives with
      longer PEO chains. The water absorption of the films increased largely with the
      increasing PEO chain length of the additives. The addition of PEO additives
      produced film surfaces that were in a gel-like state. The films demonstrated some
      extraction of the PEO additives. However, the additives with higher molecular
      weights were entrapped more stably into the PU matrix. The mechanical properties
      (tensile strength and elongation) of the films were changed by the addition of
      PEO additives, but the differences were not significant compared to the control
      PU. The platelet adhesion on the film surfaces decreased with increasing PEO
      chain length of the additives. The film surface containing additives with long
      PEO chains (chain length of 80) was particularly effective in preventing platelet
      adhesion. The effect of negatively charged sulfonate groups on the prevention of
      platelet adhesion appeared only on the film surfaces containing additives with
      short PEO chains. For longer PEO chains, the chain mobility effect was more
      dominant than the negative charge effect on the prevention of platelet adhesion.

PMID- 9549628
TI  - Chemical modification of titanium surfaces for covalent attachment of biological
      molecules.
AB  - The surface of implantable biomaterials is in direct contact with the host tissue
      and plays a critical role in determining biocompatibility. In order to improve
      the integration of implants, it is desirable to control interfacial reactions
      such that nonspecific adsorption of proteins is minimized and tissue-healing
      phenomena can be controlled. In this regard, our goal has been do develop a
      method to functionalize oxidized titanium surfaces by the covalent immobilization
      of bioactive organic molecules. Titanium first was chemically treated with a
      mixture of sulfuric acid and hydrogen peroxide to eliminate surface contaminants
      and to produce a consistent and reproducible titanium oxide surface layer. An
      intermediary aminoalkylsilane spacer molecule was then covalently linked to the
      oxide layer, followed by the covalent binding of either alkaline phosphatase or
      albumin to the free terminal NH2 groups using glutaraldehyde as a coupling agent.
      Surface analyses following coating procedures consisted of X-ray photoelectron
      spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force
      microscopy (AFM). Enzymatic activity of coupled alkaline phosphatase was assayed
      colorimetrically, and surface coverage by bound albumin was evaluated by SEM
      visualization of colloidal gold immunolabeling. Our results indicate that the
      linkage of the aminoalkylsilane to the oxidized surface is stable and that bound
      proteins such alkaline phosphatase and albumin retain their enzymatic activity
      and antigenicity, respectively. The density of immunolabeling for albumin
      suggests that the binding and surface coverage obtained is in excess of what
      would be expected for inducing biological activity. In conclusion, this method
      offers the possibility of covalently linking selected molecules with known
      biological activity to oxidized titanium surfaces in order to guide and promote
      the tissue healing that occurs during implant integration in bone and soft
      tissues.

PMID- 9549629
TI  - Polymyxin B inhibits biphasic calcium phosphate degradation induced by
      lipopolysaccharide-activated human monocytes/macrophages.
AB  - Numerous cell types, such as monocytes and osteoclasts, are involved in calcified
      matrix degradation. In this context, calcium-phosphate ceramics present similar
      degradation processes in vivo and in vitro to those found in a natural calcified
      substrate. As the monocyte/macrophage lineage is among the first cells to appear
      in ceramic implantation sites, it is a key protagonist in inflammatory reaction
      and biodegradation mechanisms. This study investigated the ability of human
      monocytes/macrophages activated by various agents [lipopolysaccharides (LPS),
      polymyxin B (PMB)] to degrade biphasic calcium-phosphate ceramics. PMB sulfate is
      a bacteriostatic antibiotic that modulates LPS-induced cell activities in vivo
      and in vitro. Degradation pits (about 10 microns) produced on the pellet surface
      by these monocytes were discrete, with well defined margins. LPS increased the
      degradation of calcium-phosphate ceramic (number of lacunae, mean pellet surface
      area degraded) in a dose-dependent manner whereas polymyxin B downmodulated it
      significantly. The addition of 2 micrograms/mL of polymyxin B reduced the number
      of degradation lacunae and the extent of degraded surface area induced by 0.1
      microgram/mL LPS by 87% and 64%, respectively. Thus this cell culture system can
      be very useful in the study of cellular degradation of biomaterials and of the
      influence of therapeutic agents that may modulate these cell activities.

PMID- 9549630
TI  - Defining the maximum tolerated dose: investigator, academic, industry and
      regulatory perspectives.

PMID- 9549631
TI  - Prevention and treatment of stroke: where do we stand?

PMID- 9549632
TI  - Elevation of liver enzymes in multiple dose trials during placebo treatment: are
      they predictable?
AB  - The present study examined the increase in transaminases, especially in ALT in
      young healthy males during placebo treatment in phase I multiple dose trials. The
      primary objective was to investigate whether volunteers showing increasing ALT
      levels also present characteristic patterns of demographic data, laboratory
      parameters, and vital signs. The secondary objective was to determine whether
      there is a possibility to predict increases of ALT during a trial by analyzing
      demographic data and baseline levels of routine safety laboratory parameters and
      vital signs. In a meta-analysis of 13 placebo-controlled multiple dose phase I
      studies, volunteers showing elevations of ALT during placebo treatment were
      compared with those presenting no clinically significant changes of ALT levels.
      Demographic data as well as routine safety laboratory values and vital signs
      measured at screening and on the first day of the in-house stay were subject to
      the analysis. Using Wilcoxon's rank sum test, significant differences between ALT
      susceptibles and ALT-nonsusceptibles were found for baseline values (mean values
      of screening and the first day of the in-house stay) of ALT, gamma GT, AST/ALT,
      and AST/ gamma GT. Differences found for the screening values of the heart rate
      were statistically rather than clinically significant. Cut-off values were found
      for baseline levels of ALT and AST/ALT ratio. Their use resulted in a sensitivity
      of 73% and a specificity of 74% with regard to predictability of ALT levels
      increasing during the trial.

PMID- 9549633
TI  - A pharmacokinetic-pharmacodynamic model of d-sotalol Q-Tc prolongation during
      intravenous administration to healthy subjects.
AB  - The objective of this study was to assess the pharmacokinetics and
      pharmacodynamics of the dextro (d-) isomer of sotalol, a class III antiarrhythmic
      agent, in healthy young men and women after a single intravenous bolus dose. The
      design was open-label, randomized, parallel group. Each group (4 men and 4 women)
      received either 0.5, 1.5, or 3.0 mg/kg d-sotalol as an intravenous infusion for 2
      minutes. Serial measurements of the d-sotalol plasma concentration and the Q-Tc
      interval data were recorded before, during, and for 72 hours after drug
      administration. The pharmacokinetics of d-sotalol were found to be well described
      by a three-compartment model with linear elimination clearance from the central
      compartment. There were no significant differences in the elimination clearance
      or volume of the central compartment between dose levels or between men and
      women. However, women were found to have a lower steady-state volume of
      distribution than men (1.20 L/Kg versus 1.43 L/Kg). The Q-Tc versus d-sotalol
      plasma concentration data were fitted to a model that assumed a distinct "effect
      compartment" and sigmoidal Emax response. The baseline Q-Tc, determined from the
      fittings, was found to be significantly higher in women (0.40 versus 0.38
      seconds). The effect compartment clearance was found to be highly variable, with
      a median of 12.3 (range, 0.2-671,300) L/h. There were statistically significant
      differences in the effect compartment clearance by dose among men and by gender
      at a dose of 1.5 mg/kg. There were no significant differences detected between
      dose groups or genders for the d-sotalol effect site concentration at one half
      the maximum Q-Tc prolongation from baseline (EC50), EMAX, (the maximum Q-Tc
      prolongation from baseline) or the Hill coefficient. In conclusion, the
      pharmacokinetics of d-sotalol after intravenous administration are independent of
      dose and gender, because the difference between men and women in volume of
      distribution at steady-state is not clinically significant. The pharmacodynamics
      of Q-Tc prolongation produced by d-sotalol appear to be independent of dose and
      gender; however, there is considerable variability in the time course of effects
      on Q-Tc between individuals.

PMID- 9549634
TI  - Clinical utility of long-term enalapril/diltiazem ER in stage 3-4 essential
      hypertension. Long-term Use of Enalapril/Diltiazem ER in Stage 3-4 Hypertension
      Group.
AB  - The use of angiotensin converting enzyme inhibitors and calcium channel blockers,
      as monotherapies and in combination, is common in the management of hypertension.
      Clinical studies have documented the augmentation of blood pressure reduction
      when these agents are combined compared with the individual agents, in short-term
      studies. In the present investigation, 93 patients with stage 3-4 essential
      hypertension, who successfully completed a short-term double-blind study,
      participated in a 40-week open-label treatment phase. The patients were
      maintained on their previous doses of enalapril/diltiazem ER (E/D) with or
      without additional antihypertensive medications. Doses of medication could be
      adjusted as necessary for blood pressure control. Of the 93 patients, 68% were
      male and 82% were white; they averaged 52.7 years of age and had a baseline mean
      sitting blood pressure (SiBP) of 167/111 mmHg. The use of E/D alone (n = 14)
      reduced mean SiBP by 14.5/14.4 mmHg from baseline, whereas the use of E/ D with
      other agents (n = 79) decreased it by 27/20.5 mmHg from baseline. E/D alone or in
      combination with other drugs was well-tolerated, and no serious adverse events
      were noted. This long-term open-label study demonstrated that the E/D combination
      alone or with the addition of other antihypertensive drugs was effective, safe,
      and well-tolerated after prolonged administration.

PMID- 9549635
TI  - Renal dysfunction does not alter the pharmacokinetics or LDL-cholesterol
      reduction of atorvastatin.
AB  - The objective of this study was to determine the effects of renal dysfunction on
      the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Nineteen subjects with
      calculated creatinine clearances ranging from 13 mL/min to 143 mL/min were
      administered 10 mg atorvastatin daily for 2 weeks. Pharmacokinetic parameters and
      lipid responses were analyzed by regression on calculated creatinine clearance.
      Correlations between steady-state atorvastatin pharmacokinetic or pharmacodynamic
      parameters and creatinine clearance were weak and, in general, did not achieve
      statistical significance. Although the elimination rate constant, lambda z
      (0.579), was significantly correlated with creatinine clearance, neither maximum
      plasma concentration (Cmax, -0.361) nor oral clearance (Cl/F, 0.306) were; thus,
      steady-state exposure is not altered. Renal impairment has no significant effect
      on pharmacodynamics and pharmacokinetics of atorvastatin.

PMID- 9549637
TI  - Pharmacokinetics of isosorbide dinitrate in healthy volunteers after 24-hour
      intravenous infusion.
AB  - No studies have examined the pharmacokinetics of isosorbide dinitrate (ISDN)
      after infusion of long duration, even though such infusions are used in patients.
      We therefore measured ISDN and its active metabolites, isosorbide-5-mononitrate
      (IS5MN) and isosorbide-2-mononitrate (IS2MN), in plasma of 9 healthy volunteers
      who received a continuous intravenous infusion of ISDN for 24 hours at a dose
      rate that lowered diastolic blood pressure by 10% during the first 30 minutes of
      infusion. All subjects tolerated the infusion except one who experienced
      intolerable headache. Five subjects received 1 microgram.min-1.kg-1, one 2
      micrograms.min-1.kg-1, and two 4 micrograms.min-1.kg-1 ISDN, whereas the full
      rate of 6 micrograms.min-1.kg-1 was used continuously in one subject. At all
      infusion rates the plasma concentrations of ISDN were higher at 24 hours than at
      earlier times, suggesting that a steady-state condition had not been reached at
      that time. The same was true for the mononitrate metabolites, which reached
      higher plasma concentrations and were cleared more slowly than the parent
      compound after the end of the infusion. Apparent elimination half-lives of ISDN,
      IS2MN, and IS5MN were 67 +/- 10 minutes, 115 +/- 13 minutes, and 272 +/- 38
      minutes, respectively. Comparison of low-rate infusions (1 and 2 micrograms.min
      1.kg-1) with high-rate infusions (4 and 6 micrograms.min-1.kg-1) showed that the
      plasma concentration ratios at 24 hours of mononitrate metabolites to parent drug
      and apparent plasma clearance of ISDN were almost halved at the higher infusion
      rates.

PMID- 9549636
TI  - Single- and multiple-dose pharmacokinetics of riluzole in white subjects.
AB  - Riluzole is a novel neuroprotective agent that has been developed for the
      treatment of amyotrophic lateral sclerosis. A series of studies was undertaken to
      establish its pharmacokinetics on single- and multiple-dose administration in
      young white male volunteers. The mean absolute oral bioavailability of riluzole
      (50-mg tablet) was approximately 60%. Maximum plasma concentration (Cmax) and
      area under the concentration-time curve (AUC) values were linearly related to
      dose for the range studied. Cmax occurred at 1.0 hour to 1.5 hours after
      administration. Plasma elimination half-life appeared to be independent of dose.
      After repeated administration of 100 mg riluzole for 10 days, some
      intraindividual variability in bioavailability was seen. A high-fat meal
      significantly reduced the rate (tmax = 2 hours compared with 0.8 hours; Cmax =
      216 ng.mL-1 compared to 387 ng.mL-1) and extent of absorption (AUC = 1,047
      ng.hr.mL-1 versus 1,269 ng.hr.mL-1). With multiple-dose administration, riluzole
      showed dose-related absorption, although the terminal plasma half-life was
      prolonged slightly. Steady-state plasma concentrations were achieved within 5
      days. Steady-state trough plasma concentrations were significantly higher with a
      75-mg dose twice daily than with a 50-mg dose three times daily, although AUC
      values did not differ.

PMID- 9549638
TI  - Pharmacokinetics of fosinoprilat in Chinese and whites after intravenous
      administration.
AB  - The pharmacokinetics of fosinoprilat was studied in 12 healthy Chinese men after
      a 7.5 mg intravenous dose of fosinoprilat. The data were compared with those from
      an earlier study using the same protocol in nine healthy white men. Blood and
      urine samples were obtained before and at various time intervals after
      fosinoprilat administration up to 24 hours and 48 hours, respectively.
      Pharmacokinetic parameters were calculated by fitting the plasma or serum
      concentrations to a three-compartment model. The total clearance (Clt), renal
      clearance (ClT), and nonrenal clearance (ClNR) were significantly lower in
      Chinese (16.29 +/- 6.92, 6.85 +/- 2.97, and 9.44 +/- 5.08 mL.hr-1.kg-1) than
      those obtained in whites (29.88 +/- 6.36, 13.55 +/- 3.45, and 16.33 +/- 5.07
      mL.hr-1.kg-1). The Chinese subjects had a significantly lower volume of
      distribution (Vc [volume of distribution of central compartment] and Vdss [volume
      of distribution at steady state]) (29.38 +/- 21.12 and 73.67 +/- 40.20 mL/kg)
      than white men (58.14 +/- 15.01 and 152.49 +/- 24.89 mL/kg). The Chinese men also
      had a shorter elimination half-life than whites, although not statistically
      significant. The respective half-lives in Chinese and whites were 5.51 +/- 1.53
      and 8.24 +/- 1.99 hours. The significant differences in ClNR and ClR may be
      related to lower liver elimination function and lower kidney excretory function,
      respectively. Plasma protein binding may contribute to part of the difference in
      the volume of distribution. Chinese men have smaller volume of distribution and
      clearances of fosinoprilat after intravenous administration compared with white
      men. The cumulative urine excretion of fosinoprilat was not different between
      Chinese and whites. Chinese may require a lower fosinoprilat dosage to obtain
      plasma concentrations similar to whites after intravenous administration.
      However, since a relatively high variation was found in fosinopril oral
      absorption, the oral dosage of fosinopril for Chinese and whites may not be
      different. Further study is obviously needed to elucidate whether the
      pharmacodynamic effect may be different between Chinese and whites.

PMID- 9549639
TI  - Chelation therapy in cardiovascular disease: ethylenediaminetetraacetic acid,
      deferoxamine, and dexrazoxane.
AB  - This review was conducted to assess whether there is sufficient evidence for the
      clinical use of chelation therapy in cardiovascular disease based on original
      articles and abstracts published in the last 30 years, with emphasis placed on
      the most recent placebo-controlled studies. Articles postulating the mechanisms
      of chelation also were included. The majority of the literature focused on three
      chelators in particular, ethylenediaminetetraacetic acid (EDTA), deferoxamine,
      and dexrazoxane (ICRF-187). Historically, much has been written on the beneficial
      effects of EDTA. However, there are few controlled studies, and the mechanism of
      action of EDTA is poorly understood. Although studies of deferoxamine are more
      recent, most of the research is limited to animals and ex vivo models. Recently,
      dexrazoxane was approved, but only for parenteral use for reducing the incidence
      and severity of cardiomyopathy associated with doxorubicin administration in
      women with metastatic breast cancer. Given these limitations, it is concluded
      that more controlled studies are required to determine the efficacy of chelation
      therapy in cardiovascular disease before it can be used broadly in the clinical
      setting.

PMID- 9549640
TI  - Protease inhibitors as inhibitors of human cytochromes P450: high risk associated
      with ritonavir.
AB  - Four protease inhibitor antiviral agents (ritonavir, indinavir, nelfinavir,
      saquinavir) were evaluated as in vitro inhibitors of the activity of six human
      cytochromes using an in vitro model based on human liver microsomes. Ritonavir
      was a highly potent inhibitor of P450-3A activity (triazolam hydroxylation),
      having inhibitory potency slightly less than ketoconazole. Indinavir was also a
      potent 3A inhibitor, while nelfinavir and saquinavir were less potent. Ritonavir
      had high inhibition potency against cytochrome P450-2C9 (tolbutamide
      hydroxylation), -2C19 (S-mephenytoin hydroxylation), and -2D6 (dextromethorphan O
      demethylation and desipramine hydroxylation), while the other protease inhibitors
      had one or more orders of magnitude lower inhibitory activity against these
      reactions. None of the protease inhibitors had important inhibitory potency
      against P450-1A2 (phenacetin O-deethylation) or -2E1 (chlorzoxazone
      hydroxylation). Thus, among available protease inhibitors, ritonavir carries the
      highest risk of incurring drug interactions due to inhibition of cytochrome P450
      activity.

PMID- 9549642
TI  - Pharmacokinetics of metoclopramide in neonates.
AB  - Despite its wide use as a prokinetic agent in neonates and infants with
      gastroesophageal reflux (GER), the pharmacokinetics of metoclopramide have not
      been characterized in this pediatric subpopulation. A single-dose pharmacokinetic
      study of oral metoclopramide (0.1 to 0.15 mg/kg) was performed in 10 fasted
      premature infants (weight 1.1 to 3.2 kg) ranging from 31 to 40 weeks
      postconceptional age. Metoclopramide was quantitated from repeated blood samples
      (n = 9 over 24 hours) by high-performance liquid chromatography. A one
      compartment open model with first-order absorption best described the plasma
      concentration-time data. No correlations were observed between gestational,
      postnatal, or postconceptional age and any of the pharmacokinetic parameters
      studied. Comparison of the pharmacokinetic parameters from the study cohort and
      those reported previously from a similar study of older infants revealed no
      statistically significant differences. However, a prolonged apparent plasma
      clearance (Cl/F) of metoclopramide was observed in 30% of the infants studied,
      and the mean Cl/F and apparent steady-state volume of distribution (Vdss/F) were
      approximately 1.4- and 2.1-fold higher, respectively, than values reported in
      previous studies of metoclopramide disposition in adults. These data suggest that
      metoclopramide pharmacokinetics may exhibit a developmental dependency. Thus, a
      metoclopramide dose of 0.15 mg/kg given orally every 6 hours is recommended for
      the initiation of prokinetic therapy with this agent in infants who are < or = 31
      weeks postconceptional age.

PMID- 9549641
TI  - Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro:
      dominance of CYP 2C19 and 3A4.
AB  - The human cytochromes P450 (CYPs) mediating amitriptyline N-demethylation have
      been identified using a combination of enzyme kinetic and chemical inhibition
      studies. Amitriptyline was N-demethylated to nortriptyline by microsomes from
      cDNA transfected human lymphoblastoid cells expressing human CYPs 1A2, 2C9, 2C19,
      2D6, and 3A4. CYP 2E1 showed no detectable activity. While CYP 2C19 and CYP 2D6
      showed high affinity, CYP 3A4 showed low affinity; CYP 2C9 and 1A2 showed
      intermediate affinities. Based on these kinetic parameters and estimated relative
      abundance of the different CYPs in human liver, CYP 2C19 was identified as the
      major amitriptyline N-demethylase at low (therapeutically relevant) amitriptyline
      concentrations, whereas CYP 3A4 may be more important at higher amitriptyline
      concentrations. Chemical inhibition studies with ketoconazole and omeprazole
      indicate that CYP 3A4 is the major amitriptyline N-demethylase at 100 mumol/L
      amitriptyline, while CYP 2C19 is equally important at a substrate concentration
      of 5 mumol/L. The CYP 1A2 inhibitor alpha-naphthoflavone and the CYP 2C9
      inhibitor sulfaphenazole produced much less inhibition of amitriptyline N
      demethylation at both substrate concentrations. Quinidine produced no detectable
      inhibition. The kinetics of amitriptyline N-demethylation by human liver
      microsomes were consistent with a two enzyme model, with the high affinity
      component exhibiting Michaelis Menten kinetics and the low affinity component
      exhibiting Hill enzyme kinetics. No difference was apparent in the kinetics of
      amitriptyline N-demethylation in two liver samples with low levels of CYP 2C19
      activity compared with two other samples with relatively normal 2C19 activity.
      This may reflect the importance of higher substrate concentration values in
      estimation of kinetic parameters in vitro.

PMID- 9549643
TI  - Pharmacokinetics and protein binding of eprosartan in healthy volunteers and in
      patients with varying degrees of renal impairment.
AB  - This was an open-label, parallel group study to compare the pharmacokinetics of
      multiple oral doses of eprosartan in subjects with normal renal function (Clcr >
      80 mL/min; n = 8) and patients with mild (Clcr 60-80 mL/min; n = 8), moderate
      (Clcr 30-59 mL/min; n = 15), or severe (Clcr < 30 mL/min; n = 3) renal
      insufficiency. Each subject received oral eprosartan 200 mg twice daily for 6
      days and a single dose on day 7. Mean total maximum concentration (Cmax) and area
      under the concentration-time curve from 0 to 12 hours (AUC0-12) were similar for
      healthy subjects and those with mild renal impairment, but were an average of 25%
      to 35% and 51% to 55% greater for patients with moderate and severe renal
      impairment, respectively, compared with healthy subjects. Mean renal clearance
      (Clr), which was similar for healthy subjects and patients with mild renal
      impairment, was decreased an average of 41% and 95% in the groups with moderate
      and severe renal impairment, respectively, compared with normal subjects.
      Eprosartan was highly bound to plasma proteins in all groups; however, the
      unbound fraction was increased approximately two-fold in the group with severe
      renal impairment. Mean unbound Cmax and AUC0-12 were an average of 53% to 61% and
      185% to 210% greater for the patients with moderate and severe renal impairment,
      respectively, compared with healthy subjects. Headache was the most common
      adverse experience reported in all subgroups. Eprosartan was safe and well
      tolerated regardless of degree of renal impairment. Cmax and AUC were increased
      and renal clearance decreased in patients with moderate to severe renal
      impairment in comparison to healthy subjects and patients with mild renal
      impairment. However, based on the moderate renal clearance and known safety
      profile of eprosartan, it is not necessary to adjust the dose of eprosartan in
      patients with renal insufficiency.

PMID- 9549644
TI  - Accumulation of fluconazole in scalp hair.
AB  - The accumulation in scalp hair of the antimycotic triazole, fluconazole, was
      studied during and after administration. Fluconazole 50 mg was administered to 12
      healthy subjects as a single capsule each day for 28 days. The concentration of
      fluconazole 5 hours after administration was measured in different 1-cm sections
      of scalp hair at intervals during treatment and for 6 months after the end of
      treatment. In each section of scalp hair the concentration of fluconazole
      increased during treatment and was consistently higher than values found in
      plasma. For example, the mean concentration in the first hair section on day 28,
      19.8 micrograms/g, corresponded to a mean penetration ratio relative to plasma of
      9.42. During administration, the maximal concentration of fluconazole was found
      in the first hair section. After cessation of administration, the measured
      concentrations of fluconazole decreased and greater concentrations were found in
      the distal hair sections, presumably as a result of hair growth. Fluconazole was
      detectable, however, in the hair of 9 of the 12 subjects even 6 months after
      treatment. The mean concentration of fluconazole in hair bulbs on day 28 was 12.1
      micrograms/g (n = 6), corresponding to a mean penetration ratio of 5.99. In a
      second study, fluconazole was administered as a single oral 150-mg capsule per
      week for 4 weeks to a group of 8 healthy subjects. The mean fluconazole
      concentration in whole scalp hair 5 hours after the last dose was 3.2
      micrograms/g.

PMID- 9549645
TI  - Pharmacokinetics of multiple-dose oral cilostazol in middle-age and elderly men
      and women.
AB  - Cilostazol is being developed for the treatment of intermittent claudication due
      to peripheral arterial disease (PAD). This study was conducted to investigate the
      effects of age and gender on the pharmacokinetics of cilostazol after multiple
      dose administration. It was an open label, multiple-dose study of cilostazol
      administered to male and female subjects 50 years of age and older at a dose of
      100 mg (oral tablet) twice daily for 7 days. Equal numbers of healthy male and
      female (7 per group), nonsmoking subjects stratified into age groups of 50 to 59
      years, 60 to 69 years, and 70 years or older were enrolled. Serial plasma samples
      were obtained. Data were analyzed by model-independent methods. Cilostazol was
      absorbed at a moderate rate, with peak plasma concentrations occurring at an
      overall mean of 2.4 hours after administration. Cilostazol is extensively bound
      (95%), primarily to albumin. A trend toward increasing cilostazol free fraction
      with age was observed in the male subjects, which was explained by a decrease in
      plasma albumin concentration with age. Differences in plasma protein binding
      between age and gender groups (less than 15%) are not expected to have any
      clinical significance. Plasma cilostazol concentrations reached steady state by
      day 4. The pharmacokinetic characteristics of cilostazol were not affected by age
      or gender.

PMID- 9549646
TI  - Vasoreactivity in pre- and postmenopausal women: evaluation by pharmacodynamic
      modeling.
AB  - Postmenopausal women experience an increase in cardiovascular mortality and
      morbidity compared with their premenopausal counterparts. This study was
      undertaken to develop a pharmacodynamic model to determine whether vascular
      reactivity in postmenopausal women differed from that in premenopausal women.
      Eleven subjects in each group were recruited. Graded doses of norepinephrine and
      insulin were infused via the dorsal hand vein. Venous diameter was measured by
      ultrasound. Dosage and venous diameter were fit to a Hill-type pharmacodynamic
      model in which norepinephrine acts as a vasoconstrictor and insulin counteracts
      varying fractions of norepinephrine constriction. Fitted pharmacodynamic
      parameters for norepinephrine did not differ uniformly between groups, but at
      norepinephrine infusion rates between 14 and 46 ng/mL, postmenopausal women
      demonstrated increased norepinephrine-induced vasoconstriction. Also, the modeled
      maximal response to insulin (Emaxi) was greater in premenopausal women. By
      stepwise linear regression, maximal response to insulin was found to be related
      to menopausal status and diastolic blood pressure. Postmenopausal women showed
      differences in vasoreactivity that may have important implications in the
      pathogenesis of hypertension.

PMID- 9549647
TI  - Droperidol elimination after cardiopulmonary bypass surgery.
AB  - A high-dose (0.75 to 2.8 mg/kg) pharmacokinetic study of droperidol was
      undertaken in patients during the recovery phase after cardiac surgery involving
      hypothermic cardiopulmonary bypass (CPB). The elimination half-life of droperidol
      in these patients, determined from concentration-time data obtained after CPB,
      was significantly prolonged relative to previously reported mean values in
      younger surgical patients not undergoing CPB and receiving lower doses of the
      drug (0.05-0.20 mg/kg). On stratification of the patients by droperidol dose,
      there was an inverse correlation between the size of the dose and the elimination
      half-life of droperidol: mean half-life decreased as mean dose increased. This
      difference in elimination half-life was not related to the duration of the CPB
      procedure, or the total anesthetic time, both of which were not significantly
      different between the patient groups receiving the three different doses of
      droperidol. The magnitude or duration of hypothermia after CPB did not differ
      between the three patient groups. The differences in half-lives are more likely
      due to the clinical condition of the patients, such that the patients who
      received the higher doses of droperidol were also judged clinically to be less
      ill and thus eliminated droperidol more efficiently. This hypothesis, however,
      could not be supported due to the small number of patients studied. The results
      obtained in this study indicate that droperidol elimination is significantly
      prolonged after high-dose administration to elderly patients undergoing
      hypothermic CPB procedures during cardiac surgery.

PMID- 9549648
TI  - Steady-state pharmacokinetics of zonisamide, an antiepileptic agent for treatment
      of refractory complex partial seizures.
AB  - A 56-day pharmacokinetic study of zonisamide was conducted in 24 healthy
      volunteers. Steady state was achieved in 29 days including two dose escalations,
      and in an average of 15 days from the last dose adjustment. Twice-daily
      administration of 200 mg every 12 hours produced a 14% serum level fluctuation at
      steady state. After once-daily administration of 400 mg, a 27% serum level
      fluctuation was observed. The terminal-phase half-life after the last dose was 63
      to 69 hours, which is consistent with the half-life of 52 to 60 hours found in
      single-dose studies. This result demonstrates that zonisamide is not an
      autoinducer. Serum oral clearance of 0.60 to 0.71 L/hr (0.121-0.132 mL/min/kg)
      was similar to that observed in other multiple-dose studies.

PMID- 9549649
TI  - Efficacy of intravenous granisetron in suppressing the bradycardia and
      hypotension associated with a rabbit model of the Bezold-Jarisch reflex.
AB  - This study investigated whether granisetron, a 5-HT3 receptor antagonist, can
      alter the Bezold-Jarisch reflex (i.e., hypotension and inappropriate heart rate
      slowing). A hemorrhagic rabbit model that has been shown to induce the Bezold
      Jarisch reflex was used. In 11 rabbits (3.8 kg), catheters were placed in the
      carotid arteries one day before experimental hemorrhage. On the day of the study,
      the rabbits were given intravenous granisetron (50 micrograms/kg) or an equal
      volume of saline. Five minutes after administration of granisetron or saline,
      hemorrhage was induced by continuous blood withdrawal at 5 mL/min and blood
      pressure (BP) and heart rates were obtained at frequent intervals until systolic
      BP declined to 80 mmHg. Six rabbits received saline and five granisetron. An
      average of 77.6 mL +/- 16.4 mL of blood was removed in the group receiving
      granisetron (compared with 56.5 mL +/- 13.1 mL for the saline group) before
      achieving the target systolic BP of 80 mmHg. The group receiving granisetron
      demonstrated the same ability to increase their heart rate from baseline as the
      saline group. However, the granisetron group had a final heart rate that was
      closer to their maximal heart rate than the saline group. In this animal model,
      granisetron was significantly more effective at preventing inappropriate heart
      rate slowing and allowed significantly more blood to be removed before reaching
      the target blood pressure. This implies that granisetron may be effective in
      preventing vasovagal syncope, although further study should be carried out to
      verify these potentially interesting findings.

PMID- 9549650
TI  - Effect of troglitazone on steady-state pharmacokinetics of digoxin.
AB  - Twelve healthy subjects participated in a study to determine the effect of
      multiple doses of troglitazone on the steady-state pharmacokinetics of digoxin.
      Subjects received digoxin 0.25 mg orally once daily on days 1 through 20 and 400
      mg of troglitazone orally once daily on days 11 through 20. Serial plasma samples
      and 24-hour urine samples collected before and after the doses on days 10 and 20
      were analyzed for digoxin using a radioimmunoassay method. Eleven subjects
      completed the study. Administration of multiple oral doses of digoxin and
      troglitazone was well tolerated. Mean values for maximum concentration (Cmax),
      time to Cmax (tmax), and area under the concentration-time curve from 0 to 24
      hours (AUC0-24) of digoxin on day 10 were similar to those on day 20. Mean day 10
      digoxin values for minimum concentration (Cmin), apparent oral clearance (Cl/F),
      total urinary excretion from 0 to 24 hours (Ae0-24), and renal clearance (Clr)
      were also similar to corresponding values on day 20. Thus, concomitant
      administration of multiple-dose troglitazone does not alter the steady-state
      pharmacokinetics of digoxin.

PMID- 9549651
TI  - Evaluation of the potential interaction between felbamate and erythromycin in
      patients with epilepsy.
AB  - Effects of erythromycin on hepatic CYP450 3A4 isozymes can profoundly influence
      the metabolism of many therapeutic agents. An open-label, randomized, two-period,
      crossover study was therefore conducted to evaluate the pharmacokinetics of
      felbamate before and after a concurrent 10-day regimen (333 mg three times daily)
      of erythromycin. Patients were receiving either 3,000 or 3,600 mg/day felbamate
      monotherapy for treatment of epilepsy. Mean dose-normalized values for maximum
      concentration (Cmax) and area under the concentration-time curve (AUC tau) of
      felbamate were not statistically different in patients taking felbamate as
      monotherapy than in patients after erythromycin coadministration. Estimates of
      time to Cmax (tmax), minimum concentration (Cmin), apparent clearance (Cl/kg),
      average concentration (Cav), and degree of fluctuation (DFss) were likewise
      unchanged. The incidence of mild and moderate adverse events increased during
      coadministration of the two drugs. Because patients with epilepsy can not be
      treated with erythromycin alone, it could not be determined whether the adverse
      events were attributable to erythromycin or to the combination of the two drugs.
      Steady-state pharmacokinetic parameters of felbamate were not influenced by
      erythromycin coadministration.

PMID- 9549652
TI  - (R)- ketoprofen in clinical trials.

PMID- 9549653
TI  - Stereoselective pharmacokinetics and inversion of (R)- ketoprofen in healthy
      volunteers.
AB  - The pharmacokinetics of ketoprofen enantiomers were evaluated after 25-, 50-, and
      100-mg doses of (R)- ketoprofen and 100 mg of racemic ketoprofen in 25 healthy
      volunteers (12 male and 13 female). The fractional inversion (Finv) of (R)-
      ketoprofen was 8.9 +/- 3.3% using plasma data and 10.0 +/- 2.2% using urine data.
      There were small (< 5%) but significant differences between the enantiomers for
      areas under the plasma concentration-time curve (AUC) after the racemic dose (P <
      0.005). Half-lives were 130-144 minutes for (R)- ketoprofen and 132-209 minutes
      for (S)- ketoprofen. Dose proportionality in AUC and maximum plasma concentration
      (Cmax) values was noted for both enantiomers. A total of 69% of the dose was
      recovered in the urine as (R)- and (S)- ketoprofen and conjugates. The
      elimination rate constant of (R)- ketoprofen was significantly different (P <
      0.05) between men and women. Exposure to cyclooxygenase inhibiting (S)-
      ketoprofen was approximately 10% of the dose after the administration of pure (R)
      ketoprofen and was independent of gender.

PMID- 9549654
TI  - Analgesic efficacy and safety of (R)- ketoprofen in postoperative dental pain.
AB  - This double-blind, randomized, parallel-group study compared the analgesic
      efficacy and safety of single doses of (R)- ketoprofen 25 mg and 100 mg to that
      of acetaminophen 1,000 mg and placebo in 177 patients experiencing moderate to
      severe pain after surgical removal of their impacted third molars. Both (R)-
      ketoprofen 100 mg and acetaminophen 1,000 mg were significantly (P < 0.05) more
      efficacious than placebo for all summary analgesic measures. Other than a more
      rapid analgesic onset (45 minutes versus 60 minutes) for acetaminophen 1,000 mg,
      (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were statistically equivalent
      to each other. The 25 mg dose of (R)- ketoprofen appeared to approach the
      analgesic threshold dose, being numerically but not statistically superior to
      placebo for all summary measures. There were no serious adverse events observed
      in this study, with the overall incidence of side effects being somewhat less in
      the (R)- ketoprofen groups than in the acetaminophen 1,000 mg group. (R)-
      Ketoprofen possesses analgesic activity and an acceptable side-effect profile in
      the oral surgery pain model.

PMID- 9549655
TI  - Clinical endoscopic evaluation of the gastroduodenal tolerance to (R)-
      ketoprofen, (R)- flurbiprofen, racemic ketoprofen, and paracetamol: a randomized,
      single-blind, placebo-controlled trial.
AB  - Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) of the 2-arylpropionic
      acid class, causes gastroduodenal hemorrhages and erosions in 10-15% of patients.
      The (S)- enantiomer exhibits most of the anti-inflammatory properties, with
      concomitant gastrointestinal toxicity. The (R)- enantiomer, however, was recently
      found to have analgesic properties independent of prostaglandin inhibition.
      Seventy-two healthy male volunteers not receiving NSAIDs, alcohol, or anti-ulcer
      drugs, were enrolled in a randomized, investigator-blind, placebo-controlled
      trial to evaluate the gastroduodenal tolerance of (R)- ketoprofen 100 mg b.i.d.,
      (R)- flurbiprofen 100 mg b.i.d., racemic ketoprofen 100 mg b.i.d., and
      paracetamol 1,000 mg b.i.d. Gastroduodenal endoscopies at baseline and after 2.5
      days of dosing were used to detect newly occurring hemorrhages and erosions.
      Adverse events were also recorded. The incidence of submucosal hemorrhages was
      4/16 in the (R)- ketoprofen group, 5/16 in the (R)- flurbiprofen group, 12/16 in
      the racemic ketoprofen group, 1/16 in the paracetamol group, and 1/8 in the
      placebo group. The incidence of erosions was 2/16 in the (R)- ketoprofen group,
      4/16 in the (R)- flurbiprofen group, 10/16 in the racemic ketoprofen group, 0/16
      in the paracetamol group, and 2/8 in the placebo group. The differences in
      hemorrhages and erosions among treatments were statistically significant (gastric
      hemorrhages P = 0.0008; duodenal hemorrhages P = 0.00062; gastric erosions P =
      0.0004; duodenal erosions P = 0.0062, Kruskal-Wallis test). At 100 mg b.i.d., (R)
      ketoprofen caused fewer gastroduodenal hemorrhages and erosions than racemic
      ketoprofen (P = 0.019, P = 0.0112, P = 0.0097, P = 0.0139 for gastric, duodenal
      hemorrhages and gastric, duodenal erosions, respectively). The difference between
      100 mg b.i.d. (R)- ketoprofen and 100 mg b.i.d. (R)- flurbiprofen was not
      statistically significant. The dissociation between analgesic and anti
      inflammatory properties for (R)- ketoprofen suggests that it may represent a
      unique analgesic with a favorable safety profile.

PMID- 9549656
TI  - Preclinical enantioselective pharmacology of (R)- and (S)- ketorolac.
AB  - Many of the nonsteroidal anti-inflammatory drugs (NSAIDs) are marketed as racemic
      mixtures, composed of (R)- and (S)- enantiomers. Racemic NSAIDs are potent
      cyclooxygenase (COX) inhibitors only through the action of the (S)- enantiomers,
      as the (R)- enantiomers do not exhibit COX inhibition. However, the (R)-
      enantiomer of ketoprofen exhibits potent analgesic activity and minimal
      ulcerogenic potential. To extend these observations, we examined the (R)- and (S)
      enantiomers of RS- ketorolac, (S)- ketorolac exhibited potent COX1 and COX2
      enzyme inhibition, whereas (R)- ketorolac was > 100-fold less active on both COX
      subtypes. Both enantiomers did not affect norepinephrine or serotonin uptake
      sites, and nitric oxidase or lipoxygenase activities, nor did they demonstrate
      any affinity for opioid receptors (mu, delta, or kappa). In experimental models,
      (S)- ketorolac exhibited about 10-fold greater activity than (R)- ketorolac in
      the murine phenylquinone writhing model. In this model, morphine sulfate was
      effective at much lower doses, however, and neither (R)- nor (S)- ketorolac
      showed any morphine-sparing effect. In the rat gait test for analgesia in the
      foot paw after injection of brewers yeast suspension, neither (R)- nor (S)-
      ketorolac affected paw volume. However, both provoked changes in gait scores, the
      (S)- enantiomer being 30-fold more potent than the (R)- enantiomer. A similar
      reduction was observed with respect to ulcerogenic potential, measured by direct
      microscopic changes after test conclusion. These findings suggest that (R)-
      ketorolac may possess analgesic activity that is independent of COX inhibition
      and may be associated with reduced ulcerogenic potential compared to effects
      exhibited by (S)- ketorolac.

PMID- 9549657
TI  - Products approved for marketing during 1997.

PMID- 9549659
TI  - Stable isotope techniques in early drug development: an economic evaluation.
AB  - Stable isotope labeled (SIL) drug methods are compared with standard methods for
      performing early (phases I and IIa) drug development studies (mass balance,
      bioavailability, single-dose volunteer and patient, multiple-dose volunteer and
      patient). SIL methods offer considerable reduction in the cost (> 50%) and number
      of subjects (67%) required for bioavailability and multiple-dose patient studies.
      Moreover, a complete early drug development program is described for optimally
      combining SIL and standard studies, which can reduce cost by 23% and number of
      subjects by 36% compared with a program using standard methods. These reductions
      should result in development time savings of at least one year.

PMID- 9549658
TI  - The importance of arterial compliance in cardiovascular drug therapy.
AB  - Arterial compliance, defined as a change in dimension in response to a given
      change in stress, is becoming an increasingly important clinical parameter.
      Related concepts, such as distensibility, elasticity, and stiffness, and more
      traditional concepts such as resistance, afterload, and impedance need to be
      differentiated from compliance, although they are frequently (inappropriately)
      used interchangably. Many studies cannot differentiate between compliance changes
      due to a drug's effect on blood pressure and those due to a drug's effect on
      vessel wall integrity. This differentiation is important because a more
      physiologic therapy, one that benefits pulsatile and nonpulsatile flow, should be
      of greater clinical benefit than a therapy that only lowers blood pressure. A
      number of methods have been used to estimate compliance, but to date there is no
      generally agreed-on best method. There also are no longitudinal studies that
      relate abnormal compliance and drug effects to outcome. Nonetheless, patients at
      risk from a variety of disease states, such as hypertension, diabetes mellitus,
      and hypercholesterolemia, may benefit from earlier recognition of abnormal
      compliance. Earlier recognition may lead to interventions that would reduce their
      risk. This review includes a discussion of compliance and related estimates of
      blood vessel function and attempts to summarize the data currently available
      regarding the effects of cardioactive drugs on arterial compliance.

PMID- 9549660
TI  - Ignorability and parameter estimation in longitudinal pharmacokinetic studies.
AB  - In the analysis of longitudinal pharmacokinetic data, both balanced (equal number
      of samples per subject) and unbalanced data are used. It is implicitly assumed
      that the process that caused the missing data can be ignored. A simulation study
      was performed to determine the effect of ignoring the missing data (i.e.,
      "ignorability") on the accuracy and precision of parameter estimation in
      longitudinal pharmacokinetic studies. A two-compartment model with multiple
      intravenous bolus inputs was assumed. Subjects with balanced data sets had six
      samples, and those with unbalanced data had 1 to 5 samples missing (i.e.,
      supplied in a decreasing order from 5 to 1 samples). The proportion of subjects
      with 1 to 5 samples missing varied from 25% to 75% in a fixed sample size of 100.
      The effect of ignorability was studied at intersubject variability ranging from
      15% to 60% for a drug assumed to be dosed at its elimination half-life. One
      hundred replicate data sets of 100 subjects each were simulated for each missing
      data scenario. The accuracy of parameter estimation was not significantly
      affected by the amount of ignorable missing data at any given level of
      variability. However, the precision of parameter estimation was affected by the
      degree of "missingness."

PMID- 9549661
TI  - Population pharmacokinetics and pharmacodynamics of pyridostigmine bromide for
      prophylaxis against nerve agents in humans.
AB  - This study was conducted to determine the pharmacokinetics and pharmacodynamics
      of pyridostigmine given as 30 mg of pyridostigmine bromide every 8 hours in
      healthy subjects. Plasma pyridostigmine concentration and red blood cell
      acetylcholinesterase activity were measured in blood samples collected during a 3
      week period. Population analysis was performed using standard pharmacokinetic and
      pharmacodynamic models with the nonlinear mixed-effect modeling software
      (NONMEM). The pharmacokinetic model that best fit the pyridostigmine plasma
      levels was a two-compartment open model with first-order absorption, a lag time,
      and first-order elimination from the central compartment. The pharmacodynamic
      model that best fit red blood cell acetylcholinesterase activity was an
      inhibitory Emax model with an effect compartment linked to the central
      compartment. The results showed that the pharmacokinetics of pyridostigmine
      bromide are both gender and weight dependent. The pharmacodynamic effect does not
      lag significantly from the plasma concentration and returns to near normal within
      8 hours. With the present dosage regimen of 30 mg every 8 hours, 30% of
      individuals may not have red blood cell acetylcholinesterase inhibition > 10% at
      the time of the trough.

PMID- 9549662
TI  - Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with
      Alzheimer's disease.
AB  - Metrifonate is converted nonenzymatically to 2.2, dimethyl dichlorovinyl
      phosphate (DDVP), an inhibitor of acetylcholinesterase (AChE). This 21-day,
      randomized, double-blind, placebo-controlled trial of metrifonate in patients
      with Alzheimer's disease (n = 27) evaluated four doses, each administered orally
      once daily. All patients received a loading dose (LD) for 6 days followed by a
      maintenance dose (MD) for 15 days. The treatment groups were: panel 1, LD = 1.5
      mg/kg (75-135 mg), MD = 0.25 mg/kg (12.5-25 mg); panel 2, LD = 2.5 mg/kg (125-225
      mg), MD = 0.40 mg/kg (20-35 mg); panel 3, LD = 4.0 mg/kg (200-335 mg), MD = 0.65
      mg/kg (30-60 mg); and panel 4, LD = 4.0 mg/kg (200-335 mg), MD = 1.0 mg/kg (50-90
      mg). All metrifonate doses were well tolerated. Most adverse events were mild to
      moderate in intensity, gastrointestinal in nature, and transient. Mean area under
      the concentration-time curve (AUC) and maximum concentration (Cmax) for both
      metrifonate and DDVP increased in relation to dose. Metrifonate and DDVP had
      similar, largely dose-independent mean values for time to Cmax (tmax) and half
      life (t1/2). There was little or no accumulation of either metrifonate or DDVP
      with long-term administration. After 21 days of treatment, mean percent
      erythrocyte AChE inhibition was 14%, 35%, 66%, 77%, and 82% for placebo and
      panels 1 through 4, respectively. Cognitive improvement was observed with the two
      highest metrifonate doses. These results reflect favorable safety and
      pharmacokinetic profiles for the use of metrifonate in the treatment of
      Alzheimer's disease.

PMID- 9549663
TI  - Pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects.
AB  - The safety, pharmacokinetics, and pharmacodynamics of single and multiple doses
      of the angiotensin II (AII) AT1 blocker irbesartan were assessed in healthy
      subjects. In this single-center, placebo-controlled, double-blind within dose
      group, sequential, dose-ascending study, 48 men were randomized to receive
      irbesartan at doses of 150 mg, 300 mg, 600 mg, or 900 mg daily. Subjects received
      a single dose of irbesartan (n = 9 per group) or placebo (n = 3 per group),
      followed by 3 days of placebo, and then multiple doses of irbesartan or placebo
      once daily for 7 days. The values for plasma area under the concentration-time
      curve (AUC) of irbesartan were dose proportional up to 600 mg. There were no
      significant differences between the dose groups in time to maximum concentration
      (tmax) or half-life (t1/2) after single and multiple doses. After multiple doses,
      urinary recovery was significantly lower in the 600-mg and 900-mg dose groups
      compared with the 150-mg and 300-mg dose groups. Steady-state concentrations of
      irbesartan were achieved within 3 days of administration with no clinically
      important accumulation. Irbesartan produced dose-dependent increases in plasma
      renin activity and AII levels. Irbesartan was well tolerated at doses from 150 mg
      to 900 mg daily; a maximally tolerated dose was not reached. Modest decreases in
      blood pressure without orthostatic symptoms were observed at irbesartan doses of
      300 mg or higher. These results demonstrated the dose-proportionality of
      irbesartan 150 mg to 600 mg and indicated that doses up to 900 mg daily were well
      tolerated.

PMID- 9549664
TI  - Absolute bioavailability and electroencephalographic effects of conventional and
      extended-release formulations of venlafaxine in healthy subjects.
AB  - Venlafaxine is currently marketed for treatment of depressive disorders as a
      conventional tablet formulation with a twice or three times daily dosage regimen.
      The absolute bioavailability of the conventional (CF) and extended-release (XR)
      formulations and their effects on electroencephalograms (EEG) and on a visual
      analog scale (VAS) for nausea were assessed in a randomized, double-blind, four
      way crossover, placebo-controlled study of 16 healthy young men who were given
      either a single oral dose of 50 mg of CF venlafaxine, 75 mg of XR venlafaxine, or
      an intravenous dose of 10 mg of venlafaxine, or a placebo at 1-week intervals.
      The absolute bioavailability of venlafaxine was between 40% and 45% and was
      similar for both the CF and XR formulations. Venlafaxine produced central effects
      of a desipramine-like antidepressant. Regardless of formulation tested, the main
      EEG changes were an increase in fast beta (20-30 Hz) energy, which was more
      pronounced over the frontotemporal regions and extended within the full beta
      range (16-40 Hz). Maximum effect was reached at 6 hours for the CF and reached a
      plateau from 10 to 24 hours for the XR formulation. A dose-proportional increase
      in central activity, expressed as area under the effect curve (AUE) of the beta
      band, was observed between the CF (50 mg) and XR (75 mg) formulations. Compared
      with the CF tablet, the XR formulation also produced a much less intense maximum
      effect and a decrease of 63% in the AUE of nausea normalized by dose. The XR
      formulation has the same absolute bioavailability and the same central activity
      as assessed by EEG, but produced less intensive nausea than CF venlafaxine. The
      present findings suggest that a once-daily dosage regimen should be sufficient.
      This was confirmed by several clinical trials in depressive patients.

PMID- 9549665
TI  - Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed
      graft function.
AB  - The pharmacokinetics of mycophenolic acid (MPA), the immunosuppressant form of
      the prodrug mycophenolate mofetil (MMF), and the primary glucuronide metabolite,
      MPAG, were characterized in renal transplant patients with delayed graft function
      using random effects piecewise linear models. Eight patients were evaluated after
      receiving their first and subsequent daily oral doses of 1.5 g mycophenolate
      mofetil twice daily on study days 1 (n = 8), 7 (n = 8), 14 (n = 5), 21 (n = 2),
      and 28 (n = 7). The area under the concentration-time curve from zero to 12 hours
      (AUC0-12) for MPA, MPAG, MPA free fraction, and free MPA were analyzed in serial
      plasma samples using validated high-performance liquid chromatography and
      ultrafiltration procedures. Random effects piecewise linear models, fit by
      maximum likelihood methods, were applied to AUC0-12 of MPA and MPAG, MPA free
      fraction, AUC0-12 of free MPA, and serum creatinine concentration, the index of
      renal function used in this study. Two hemodialysis sessions did not lower MPA
      plasma concentration, although some MPAG was removed. The AUC0-12 of MPA
      increased as a function of time, although it was not possible to fit a
      statistical model to the data due to considerable among-patient variation in the
      pattern of increase with time. The AUC0-12 of MPAG, MPA free fraction, and AUC0
      12 of free MPA reached maximal values on day 7; each of these parameters had
      unique day 1 to 7 positive slope values and unique day 7 to 28 negative slope
      values. The average creatinine concentration was maximal at day 1 and a unique
      negative slope was obtained between days 7 and 28. Thus, this study provides
      statistical models for the alteration of AUC0-12 of MPAG, MPA free fraction, AUC0
      12 of free MPA, and serum creatinine in renal transplant patients with delayed
      graft function. These results provide evidence that renal dysfunction is
      associated with altered pharmacokinetics of MPA, particularly increased AUC0-12
      of MPAG, MPA free fraction, and AUC0-12 of free MPA. The perturbed
      pharmacokinetics normalized with improving renal function.

PMID- 9549666
TI  - Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in
      combination in healthy male volunteers.
AB  - Modafinil is a novel wake-promoting agent being developed for treatment of
      excessive daytime sleepiness associated with narcolepsy. An open, 3 x 3 Latin
      square, randomized, cross-over study was performed in healthy males to compare
      the pharmacokinetics of single-dose oral modafinil (200 mg) and methylphenidate
      (40 mg) administered alone or in combination. Blood samples were obtained for
      analysis of d- and l-threo-methylphenidate and modafinil and its acid and sulfone
      metabolites. Pharmacokinetic parameters were determined by noncompartmental
      methods, but could not be evaluated for modafinil sulfone due to plasma levels
      that were close to the assay quantitation limit. Although sporadic differences in
      plasma concentrations were observed between treatments, coadministration of
      modafinil and methylphenidate did not significantly alter the plasma
      concentrations of modafinil, modafinil acid, modafinil sulfone, or
      methylphenidate enantiomers compared with administration of these agents alone.
      Half-life (t1/2), maximum concentration (Cmax), area under the concentration-time
      curve (AUC0-infinity), total clearance (Cl/F), and apparent volume of
      distribution (Vd/F) for modafinil and t1/2, Cmax, and AUC0-infinity for modafinil
      acid were not affected by concomitant administration of methylphenidate. Small
      but statistically significant increases in time to Cmax (tmax) were observed for
      modafinil and modafinil acid after methylphenidate coadministration compared with
      modafinil alone. Modafinil coadministration did not significantly alter the
      pharmacokinetics of d- or l-threo-methylphenidate, except for a small decrease in
      Vd/F of l-threo-methylphenidate. Concomitant methylphenidate may cause a delay in
      the oral absorption of modafinil, but this delay might not be relevant
      clinically. Coadministration did not alter the extent of oral absorption and
      disposition of either agent. Therefore, a pharmacokinetic interaction between
      modafinil and methylphenidate would be unlikely.

PMID- 9549667
TI  - Paradoxical hypotension and bradycardia after intravenous arginine vasopressin.
AB  - Standard therapy for variceal bleeding includes endoscopic sclerotherapy and
      esophageal balloon tamponade. In addition, pharmacologic therapies, including
      arginine vasopressin (AVP), are frequently used in hemodynamically unstable
      patients or where sclerotherapy has been unsuccessful. A case is described herein
      of a 30-year-old woman with a history of ethanol abuse, hematemeisis, and biopsy
      proven hepatic cirrhosis in which the addition of AVP to an antivariceal regimen
      of octreotide was associated with a paradoxical episode of hypotension,
      bradycardia, and hypoxia. Indeed, within 15 minutes after initiation of an AVP
      infusion, the patient exhibited hypotension with a systolic blood pressure of 80
      mmHg, a relative bradycardia to 76 beats per minute, and a desaturation of blood
      oxygen to 84%. The AVP infusion was discontinued 2 hours later and blood
      pressure, heart rate, and oxygen saturation rapidly returned to baseline. This
      temporal correlation between the onset and termination of the physiologic effects
      and the initiation and discontinuation of the AVP infusion suggests a causal
      relationship. The paradoxical physiologic effects might reflect cardiac ischemia
      secondary to vasospasm and/or central suppression of the autonomic nervous system
      induced by AVP.

PMID- 9549668
TI  - A social interactionist view of autism and its clinical management.

PMID- 9549669
TI  - Describing the unusual behavior of children with autism.
AB  - The behaviors of children with autism have been described by professionals, by
      family members, and also by those with autism. This article analyzes four
      different types of reports that contain descriptions of those with autism: (1)
      case studies, (2) diagnostic reports and single-subject research studies, (3)
      family accounts, and (4) autobiographical descriptions. Authors describe the
      behaviors of those with autism differently depending upon their relationship with
      the person they are describing, their intended audience, their goals, and the
      genre they use for conveying their descriptions. Authors were found to use the
      following types of descriptions, to varying degrees in order to achieve their
      goals: (1) descriptions of what a child did on a particular occasion; (2)
      descriptions of what a child typically does or did; (3) descriptions of what a
      child should have done; (4) descriptions of how behavior was experienced by a
      child or family member; (5) descriptions of how a third party reported a
      behavior; (6) metaphoric descriptions of behaviors; and (7) descriptions of how
      behaviors mesh with traits often associated with autism. A detailed examination
      of how behaviors of children with autism are described indicates that the way
      someone with autism is regarded and described is strongly related to what the
      describer wants to accomplish.

PMID- 9549670
TI  - Structural patterns in conversations with a woman who has autism.
AB  - The experience of conversing with a person who has autism is often described as
      unsatisfactory. This article offers some suggestions as to why that might be.
      Conversation between an adult diagnosed as autistic and a researcher was
      transcribed and analyzed using the methodology of Conversation Analysis. The
      analysis highlights differences in conversational style between the two
      participants based on features such as topic movement, topic maintenance,
      repairs, interference from earlier structures and common collocations, overlaps,
      latching, and pauses. It is suggested that many of the features of the subject's
      talk which result in an overly repetitive style may be cognitively motivated.

PMID- 9549671
TI  - Influence of question type on response adequacy in young adults with autism.
AB  - Sources of difficulty in comprehending conversational questions for individuals
      with autism may be multifarious, given the complexity of the disorder. This study
      investigated success in responding to naturalistic conversational questions by
      six young adults with autism, using a quantitative discourse analytic method.
      Subjects, aged 19-21, who were able to converse in at least simple sentences,
      were engaged in conversation about events and activities in their lives. From the
      transcripts of these conversations, four types of questions were isolated for
      analysis: more than seven words in length; multiclausal; requiring inference; and
      indirect requests for information. It was predicted that inference-based
      questions would be more difficult than the other types. Findings did not support
      this prediction. All four types showed a higher failure rate than the overall
      failure rate for responses to conversational questions. Clinical implications
      include the need for conversational assessment of receptive language functioning
      for individuals with autism. Suggestions for such assessments are provided.

PMID- 9549672
TI  - Augmentative and alternative communication to support receptive and expressive
      communication for people with autism.
AB  - In this article the authors discuss the use of augmentative and alternative
      communication (AAC) as used to enhance comprehension and expression of people
      with autism. A theoretical model for AAC assessment and intervention planning is
      presented. Application of the model is illustrated through a case report of a 6
      year-old boy with autism who had severe expressive and receptive language
      impairments.

PMID- 9549673
TI  - An intervention technique for children with autistic spectrum disorder: joint
      attentional routines.
AB  - Virtually all children with autism are deficient in joint attentional skills. The
      impact of this deficit may be understood in the context of pragmatically based
      explanations of language acquisition. In this view, each step in the ontongeny of
      joint attention is consequential for language development. Thus, it is important
      that speech-language pathologists understand the developmental course of joint
      attention so that intervention may start at the earliest step possible. In this
      article, we review the literature on joint attention and its relationship with
      other rule systems of language. We discuss the ontogeny of joint attention in
      typical children. Finally, we describe the developmental course of joint
      attention as a framework for language intervention through the study of one case.

PMID- 9549674
TI  - Doctors should not try to ban boxing--but boxing's own ethics suggests reform.

PMID- 9549675
TI  - Treating anorexics without consent: some reservations.

PMID- 9549676
TI  - Against medical ethics: opening the can of worms.
AB  - In a controversial paper, David Seedhouse argues that medical ethics is not and
      cannot be a distinct discipline with it own field of study. He derives this claim
      from a characterization of ethics, which he states but does not defend. He claims
      further that the project of medical ethics as it exists and of moral philosophy
      do not overlap. I show that Seedhouse's views on ethics have wide implications
      which he does not declare, and in the light of this argue that Seedhouse owes us
      a defence of his characterization of ethics. Further, I show that his
      characterization of ethics, which he uses to attack medical ethics, is a
      committed position within moral philosophy. As a consequence of this, it does not
      allow the relation between moral philosophy and medical ethics to be discussed
      without prejudice to its outcome. Finally, I explore the relation between
      Seedhouse's position and naturalism, and its implications for medical
      epistemology. I argue that this shows us that Seedhouse's position, if it can be
      defended, is likely to lead to a fruitful and important line of inquiry which
      reconnects philosophy and medical ethics.

PMID- 9549678
TI  - Xenografting: ethical issues.
AB  - This paper considers the ethical issues raised by xenotransplantation under four
      headings: interfering with nature; effects on the recipient; effects on other
      humans; and effects on donor animals. The first two issues raise no insuperable
      problems: charges of unnaturalness are misguided, and the risks that
      xenotransplantation carries for the recipient are a matter for properly informed
      consent. The other two issues raise more serious problems, however, and it is
      argued that if we take seriously the risk of transferring new infectious agents
      from animal to human populations and the interests of donor animals, then a
      moratorium on xenotransplantation is called for. The paper finds that the recent
      Nuffield Council and Department of Health reports on xenotransplantation are
      insufficiently cautious in the conclusions that they draw from these
      considerations.

PMID- 9549679
TI  - Postmodernity and a hypertensive patient: rescuing value from nihilism.
AB  - Much of postmodern philosophy questions the assumptions of Modernity, that period
      in the history of the Western world since the Enlightment. These assumptions are
      that truth is discoverable through human reason; that certain knowledge is
      possible; and furthermore, that such knowledge will provide a basis for the
      ineluctable progress of Mankind. The Enlightenment project is underwritten by the
      conviction that knowledge gained through the scientific method is secure. In so
      far as biomedicine inherits these assumptions it becomes fair game for postmodern
      deconstruction. Today, perhaps more than ever, plural values compete, and
      contradictory approaches to health, for instance, garner support and acquire
      supremacy through consumer choice and media manipulation rather than evidence
      based science. Many doctors feel a tension between meeting the needs of the
      patient face to face, and working towards the broader health needs of the public
      at large. But if the very foundations of medical science are questioned, by
      patients, or by doctors themselves, wherein lies the value of their work? This
      paper examines the issues that the anti-foundationalist thrust of postmodernism
      raises, in the light of a case of mild hypertension. The strict application of
      medical protocol, derived from a nomothetic, statistical perspective, seems
      unlikely to furnish value in the treatment of an individual. The anything goes,
      consumerist approach, however, fares no better. The author argues that whilst
      value cannot depend on any rationally predetermined parameters, it can be
      rescued, and emerges from the process of the meeting with the patient.

PMID- 9549680
TI  - Advance directives for non-therapeutic dementia research: some ethical and policy
      considerations.
AB  - This paper explores the use of advance directives in clinical dementia research.
      The focus is on advance consent to participation of demented patients in non
      therapeutic research involving more than minimal risks and/or burdens. First,
      morally relevant differences between advance directives for treatment and care,
      and advance directives for dementia research are discussed. Then attention is
      paid to the philosophical issue of dementia and personal identity, and the
      implications for the moral authority of research advance directives. Thirdly, a
      number of practical shortcomings of advance directives for non-therapeutic
      dementia research are explored and attention is paid to the role of proxies. It
      is concluded that upon a closer look the initial attractiveness of advance
      directives for dementia research is lessened, and that it is doubtful whether
      these instruments can compensate for the lack of subject consent in case of non
      therapeutic dementia research involving more than minimal risks and/or burdens
      for the incompetent demented subject.

PMID- 9549681
TI  - The ethics of compulsory removal under section 47 of the 1948 National Assistance
      Act.
AB  - Orders for removal under Section 47 of the 1948 National Assistance Act are
      little discussed. However, they involve severe infringements of the civil
      liberties of those affected. It is argued that all previously presented
      justifications for the use of these orders fail. Repeal of the act is called for.
      The Law Commission has drafted alternative legislation, but this has not been
      enacted. Until this occurs local authorities, the Faculty of Public Health
      Medicine and individual public health physicians should refuse to be involved in
      its use.

PMID- 9549682
TI  - Autonomy and paternalism in geriatric medicine. The Jewish ethical approach to
      issues of feeding terminally ill patients, and to cardiopulmonary resuscitation.
AB  - Respecting and encouraging autonomy in the elderly is basic to the practice of
      geriatrics. In this paper, we examine the practice of cardiopulmonary
      resuscitation (CPR) and "artificial" feeding in a geriatric unit in a general
      hospital subscribing to jewish orthodox religious principles, in which the
      sanctity of life is a fundamental ethical guideline. The literature on the
      administration of food and water in terminal stages of illness, including
      dementia, still shows division of opinion on the morality of withdrawing
      nutrition. We uphold the principle that as long as feeding by naso-gastric (N-G)
      or percutaneous endoscopic gastrostomy (PEG) does not constitute undue danger or
      arouse serious opposition it should be given, without causing suffering to the
      patient. This is part of basic care, and the doctor has no mandate to withdraw
      this. The question of CPR still shows much discrepancy regarding elderly
      patients' wishes, and doctors' opinions about its worthwhileness, although up to
      10 percent survive. Our geriatric patients rarely discuss the subject, but it is
      openly ventilated with families who ask about it, who are then involved in the
      decision-making, and the decision about CPR or "do-not-resuscitate" (DNR) is
      based on clinical and prognostic considerations.

PMID- 9549683
TI  - Doctors, ethics and special education.
AB  - This discussion paper is drawn from a qualitative research project comparing the
      effect of special and ordinary schools on the lives of children, young people and
      their families. Special schools are recommended by health professionals who
      seldom know how ineffective these schools are. We question the beneficence and
      justice of health professionals' advice on education for children with
      disabilities and other difficulties. Cooperation with local education authorities
      (LEAs) plays a considerable part in the work of community paediatricians,
      clinical medical officers, therapists and other health professionals encountering
      children with "special needs". The "needs" range from physical disability and
      sensory impairment to learning difficulties and emotional or behavioural
      difficulties. This cooperation involves routine administrative problems, but it
      raises broad ethical issues too, particularly in respect of current tendencies in
      state schooling towards the integration or inclusion of these children in
      mainstream schools and classes.

PMID- 9549684
TI  - Freedom to box.
AB  - The british Medical Association wants to criminalise all boxing. This article
      examines the logic of the arguments it uses and finds them wanting. The move from
      medical evidence about the risk of brain damage to the conclusion that boxing
      should be banned is not warranted. The BMA's arguments are a combination of
      inconsistent paternalism and legal moralism. Consistent application of the
      principles implicit in the BMA's arguments would lead to absurd consequences and
      to severe limitations being put on individual freedom.

PMID- 9549685
TI  - Nuclear cardiology, Part I: Anatomy and function of the normal heart.
AB  - This is the first article of a four-part series on nuclear cardiology. This
      article introduces and reviews the anatomy and function of the normal heart.
      Future articles will develop the contribution of nuclear medicine techniques in
      evaluating myocardial perfusion, function and viability. This article describes
      the external and internal features of the heart and its vascularization,
      conducting system and physiological function. After reading this article, the
      reader should understand the anatomy and the function of the normal heart.

PMID- 9549686
TI  - Scintillation camera quality control, Part I: Establishing the quality control
      program.
AB  - This is the first article in a four-part series on scintillation camera quality
      control. This series of articles will include both theory and practical knowledge
      on setting up a quality control program, acceptance testing and quality control
      for planar, SPECT and special imaging procedures. On completion of this article
      the reader should be able to: (a) discuss the purpose of a quality control
      program; (b) know how to establish the performance criteria for a scintillation
      camera; (c) know how to design a quality control program; (d) be able to set up
      the schedule for the quality control program; (e) understand the economics of
      quality control; and (f) justify the expenditure of the institution's resources
      on quality control.

PMID- 9549687
TI  - Thinking nuclear medicine--PET activation.
AB  - PET activation, although restricted to a limited number of research centers, is
      currently the gold standard for mapping functional areas of the brain. This paper
      outlines how and why activation studies are performed and reviews the major uses
      of this technique. Special emphasis is on cognitive neuropsychology including the
      results of a project designed to map the areas of the brain responsible for
      controlling automatic counting and simple calculation. These fascinating studies
      are, by definition, a part of nuclear medicine. As such, we argue that knowledge
      of PET activation is an essential component of professional development and that,
      given opportunity, commitment and the will to learn, nuclear medicine
      technologists have the potential for involvement, collaboration or leadership in
      this area of research.

PMID- 9549688
TI  - Off-site determinations of effective renal plasma flow using technetium-99m-MAG3
      and single blood sampling.
AB  - This study evaluated the feasibility of determining effective renal plasma flow
      (ERPF) at an off-site central laboratory by transferring blood samples from the
      on-site laboratory. METHODS: Blood samples were obtained from 66 patients
      referred for renal imaging with 99mTc-MAG3. ERPF values were determined using the
      single blood sample method (BSM) at both on- and off-site laboratories. The ERPF
      values were classified clinically as normal or abnormal. Both the ERPF values and
      clinical classification were compared between on- and off-site laboratories.
      RESULTS: The off-site ERPF overestimated those on-site by 2.8% (paired Student's
      t-test p < 10(-5)). However, off-site ERPF values highly correlated with the
      values obtained on-site (r = 0.99; p < 10(-5)). In addition, the clinical
      classification for each patient determined at each site was identical.
      CONCLUSION: ERPF can be determined accurately off-site. This method should allow
      many nuclear medicine departments access to the ERPF determination by the BSM at
      a central off-site laboratory.

PMID- 9549689
TI  - The lung scan in patient selection for lung volume reduction surgery.
AB  - The lung scan is one of the most important diagnostic tests used for selecting
      candidates for lung volume reduction surgery (LVRS) and for determining the
      actual percentage of lung to be resected during the surgery (McKenna R, personal
      communication, 1997). This article describes the anatomical quantitation of the
      lungs. METHODS: We used automatic and manual regions of interest in the
      posterior, and both posterior obliques of lung perfusion images to calculate the
      percent function in each individual lung lobe. RESULTS: We evaluated 172 patients
      with this technique. Subsequently 136 of these patients had LVRS. CONCLUSION: The
      anatomical placement of regions of interest in the lung perfusion image aids the
      thoracic surgeon in selecting LVRS candidates and in determining the amount of
      lung to be resected during surgery.

PMID- 9549690
TI  - Occult intestinal bleeding imaged by technetium-99m-HSA-D radionuclide
      angiography: a case report.
AB  - Radionuclide angiography (RNA) with 99mTc-diethylenetriamine pentaacetic acid
      human serum albumin (99mTc-HSA-D) is a sensitive screening method for diagnosing
      systemic perfusion abnormalities. Sometimes the results produce unexpected
      information. This information is helpful when considering the clinical perfusion
      pathophysiology. Recently, we were able to detect an intestinal bleeding lesion
      clearly for a patient by using RNA.

PMID- 9549691
TI  - Dose from syringe procedures during technetium-99m radiopharmaceutical
      preparation.
AB  - We examined the dose from 99mTc contained in syringes and shielded vials to
      assess in detail the dose burdens in a central pharmacy. METHODS: Absorbed-dose
      rates at the end of the plunger of a shielded syringe, when 99mTc is contained
      either in the syringe or in a shielded vial from which the activity would be
      drawn, were measured with CaF2 dosimeters. The dose rates also were calculated
      with a Monte Carlo model. RESULTS: When activity was contained in either 3-ml or
      10-ml disposable syringes shielded by lead glass, the absorbed-dose rates were
      1.35-1.62 mGy hr-1 GBq-1 (5-6 mrad hr-1 mCi-1). When the activity was contained
      in either a shielded elution or product kit vial, the absorbed-dose rates at the
      end of the syringe plunger were about 0.40 mGy hr-1 GBq-1 (1.4-1.5 mrad hr-1 mCi
      1). These results were reproduced with reasonable accuracy by Monte Carlo
      simulations. CONCLUSION: The dose burden per unit of activity handled from 99mTc
      in procedures using syringes is likely to be two to five times larger than the
      dose burden from calibrating generator eluate. The Monte Carlo simulations
      suggest that lead K x-rays may be responsible for a significant fraction of the
      total dose to the fingers and hand of the pharmacist when lead-glass syringe
      shields are used.

PMID- 9549692
TI  - Using the ACNP Proficiency Testing Program to develop critical thinking. American
      College of Nuclear Physicians.
AB  - Critical thinking is cited as one of the essential skills for clinical practice.
      Educators need to be aware of barriers that may hinder the development of this
      skill in students and cultivate strategies to encourage it. This article
      describes one strategy to develop critical thinking. METHODS: Students
      participated in a critical thinking exercise by imaging the American College of
      Nuclear Physicians (ACNP) Renal Imaging Proficiency Test Phantom, critiquing
      their results, and comparing their results to results collected nationally in
      other nuclear medicine facilities and the true values reported by the ACNP.
      Students were instructed to review pertinent imaging principles before discussing
      the imaging results. They also were supplied with a list of questions pertinent
      to the review. RESULTS: Students experienced the complexity of designing a SPECT
      imaging protocol and how the final results are affected by the choices made by
      the technologist. They learned the importance of and method for proper matrix
      selection, determination of pixel size and the necessity for quality control.
      CONCLUSION: The imaging exercise was a successful means of helping students
      connect clinical practice with theory through the use of critical thinking.

PMID- 9549693
TI  - Technetium-99m DTPA aerosol contamination in lung ventilation studies.
AB  - Contamination of working areas by 99mTc DTPA aerosol is of concern to nuclear
      medicine technologists. This study sought to determine the extent of 99mTc DTPA
      contamination to technologists, and to localize sources of aerosol leakage so
      that methods could be identified that would minimize contamination. METHODS:
      Fifty to eighty millicuries 99mTc DTPA, diluted to a volume of 4-5 ml with normal
      saline, were injected into the nebulizing chamber of two commercially available
      inhalation aerosol systems. The patient's nostrils were clamped and a damp
      washcloth was wrapped around the patient's mouth. An alcohol swab was placed in
      the exit port of the exhaust filter in each delivery system, and the technologist
      involved wore a face mask during the inhalation phase. The patient breathed DTPA
      labeled aerosol by mouth until the counting rate in the lungs was four times
      greater than the counting rate from the pulmonary perfusion phase. Connecting
      joints of the delivery system were then wipe tested. Last, a Geiger-Mueller
      detector (pancake probe) was used to survey all device components. Readings above
      0.05 mR/hr were considered contaminated. RESULTS: The patient was the greatest
      source of leakage as determined by the damp washcloth, followed by the joints of
      the tubes of the delivery system and, finally, the system's exhaust filter.
      Contamination readings from face masks worn by technical personnel during the
      lung ventilation studies were slightly greater than 0.05 mR/hr. CONCLUSION: The
      findings support trace levels of contamination to both the technologist and room
      while performing 99mTc DTPA aerosol ventilation studies. Comparative data using
      the two delivery systems revealed little difference in sources of leakage and
      little variation in contamination measurements.

PMID- 9549694
TI  - Performance and responsibility guidelines for the nuclear medicine technologist:
      1998 revision. Society of Nuclear Medicine-Technologists.

PMID- 9549695
TI  - NMTCB 1997. Task analysis report. Nuclear Medicine Technology Certification
      Board.

PMID- 9549696
TI  - Fetal monitoring terminology.

PMID- 9549697
TI  - Something to talk about: sexual risk communication between young women and their
      partners.
AB  - OBJECTIVES: To describe sexual risk communication between young women and their
      male sexual partners and examine its impact on women's perceptions of sexual
      risk. DESIGN: The study and results reported were part of a larger descriptive,
      retrospective study in which data were collected from young women and their male
      partners via telephone interviews. PARTICIPANTS: Participants included 93
      unmarried, sexually active heterosexual women, ages 17 to 26 years, and 82 of
      their male sexual partners. The sample was predominantly white; all other ethnic
      groups were underrepresented. RESULTS: Nearly all of the women described their
      partners as "no risk" or "low risk," despite the fact that nearly half never
      discussed their partner's sexual risk histories. Women gave three primary reasons
      why sexual risk was not discussed: (a) did not know the partner well enough/too
      embarrassed to ask; (b) "knew" the partner was low risk/no need to discuss it;
      and (c) did not think of it. CONCLUSIONS: Nurses should adopt and promote the
      premise that all sexually active women are at some risk for sexually transmitted
      diseases (STDs), including human immunodeficiency virus (HIV). Furthermore,
      sexually active women should be advised to distinguish between what they think
      they know about their partners and what they actually know. As client advocates,
      nurses should empower women to recognize that they have the right to insist on
      full sexual history disclosure and STD/HIV testing, to question whether they want
      to have sexual relations, and to refuse to engage in sexual activity if they
      wish.

PMID- 9549698
TI  - Clinical presentation of women readmitted with postpartum severe preeclampsia or
      eclampsia.
AB  - OBJECTIVE: To identify symptoms that prompted a group of women readmitted for
      postpartum severe preeclampsia or eclampsia to seek medical care. DESIGN:
      Retrospective, case-control. SETTING: Tertiary-care teaching hospital. SUBJECTS:
      The study group consisted of 53 women readmitted in the postpartum period with
      severe preeclampsia or eclampsia. The control group was matched two-to-one with
      an index study participant and consisted of 106 women who had intrapartum severe
      preeclampsia or eclampsia. MAIN OUTCOME MEASURES: Patient symptoms, physical
      findings, laboratory assays. RESULTS: Neurologic complaints, malaise, and nausea
      and vomiting were reported more often in women who were readmitted than in
      mothers with intrapartum preeclampsia (all p values less than .001). Headaches
      were positively correlated with systolic, diastolic, and mean arterial blood
      pressure in women who were readmitted (all p values less than .05), although
      there was no relationship between blood pressure and headaches in the control
      group. In addition, multivariate analysis revealed that study participants were
      more likely to deliver at full term, have headaches and malaise, have normal
      platelet values, and develop seizures than mothers in the control group, chi 2 =
      155.7, p < .001. CONCLUSIONS: Women readmitted for postpartum severe preeclampsia
      or eclampsia have a clinical presentation that differs from that of intrapartum
      preeclampsia or eclampsia.

PMID- 9549700
TI  - Lifestyle factors related to postpartum weight gain and body image in bottle- and
      breastfeeding women.
AB  - OBJECTIVE: To explore the relationship of lifestyle variables to postpartum
      weight gain and body image attitudes of bottle- and breastfeeding women. DESIGN:
      Mail survey of new mothers at approximately 4 months postpartum. SETTING:
      Southwestern community. PARTICIPANTS: One hundred one bottle-feeding women (69%
      white, 20% Hispanic, 11% other) and 106 breastfeeding women (76% white, 19%
      Hispanic, 5% other) without diabetes. Bottle- and breast-feeding women did not
      differ on gestational weight gain or weight gain sustained postpartum. MAIN
      OUTCOME MEASURES: Postpartum weight gain (relative to prepregnancy weight) and
      body image attitudes. RESULTS: Feeding method (breast or bottle) was not
      associated with postpartum weight gain in the sample as a whole. Bottle-feeding
      mothers with higher postpartum gains exercised less, had higher fat intake
      habits, and were more dissatisfied with body image than mothers with lower gains.
      Breast-feeding mothers with higher and lower gains did not differ on any
      lifestyle factors. Overall lifestyle and psychologic skill in managing emotions
      were related negatively to postpartum body image dissatisfaction in both groups
      of women. CONCLUSIONS: Breastfeeding women did not differ from bottle-feeding
      women in sustained postpartum weight gain. In bottle-feeding women, lifestyle
      factors were associated with levels of weight gain. Lifestyle-focused programs
      for weight management would potentially benefit these women.

PMID- 9549699
TI  - Early postpartum discharge: how are mothers managing?
AB  - OBJECTIVE: To describe maternal concerns at 2 weeks and mothers' ability to
      function in various roles at 4 weeks postpartum. DESIGN: Subjects were mailed
      questionnaires at 2 and 4 weeks postpartum. SETTING: A mid-Atlantic hospital that
      is a part of an academic health center. PARTICIPANTS: A convenience sample of 100
      healthy women who were discharged < or = 48 hours postpartum and met the study
      criteria. MAIN OUTCOME MEASURES: Instruments included a demographic
      questionnaire, the Maternal Concerns Questionnaire, and the Inventory of
      Functional Status After Childbirth. RESULTS: Physiologic concerns during the
      early postpartum period related primarily to perineal sutures, breast care, body
      image, and fatigue. More than 25% of the women continued to experience depression
      at 2 weeks, and 40% had days at 1 month when they never got dressed. Much concern
      was expressed about the mothering role but little about interaction with the
      mate. Older maternal age was associated with a longer hospital stay, and the
      trend suggested improved functioning at 1 month with longer hospitalization. More
      than half of the participants said they would visit a nurse-run clinic during the
      1st postpartum week if given the opportunity. CONCLUSIONS: The results provide
      descriptive information about effects of early hospital discharge. Mothers
      discharged in 48 hours or less adjust to motherhood without the education and
      assessment that was formerly possible with extended hospitalization. The current
      study reinforces the need for nurses to explore strategies in hospitals or
      communities to provide early care for postpartum mothers.

PMID- 9549701
TI  - Postpartum teaching priorities: the viewpoints of nurses and mothers.
AB  - OBJECTIVE: To compare mothers' and nurses' perceptions of postpartum learning
      needs and effective teaching modalities. DESIGN: Cross-sectional research design.
      Mothers were given a questionnaire during their postpartum stay to rate how
      important it was for them to learn about 44 maternal-infant topics before
      discharge. Nurses rated similar items on the basis of their perception of what is
      most important for mothers to learn during their postpartum stay. SETTING:
      Postpartum units in six hospitals that are part of a large midwestern health care
      system. PARTICIPANTS: English-speaking women who delivered either vaginally or by
      cesarean section without complications and the nurses on their postpartum units.
      MAIN OUTCOME MEASURES: Identification of preferred topics and methods for
      postpartum teaching. RESULTS: Mothers and nurses agreed that topics related to
      immediate physical health needs were most important. Unmarried mothers considered
      topics related to personal care and mobility as particularly important. First
      time mothers rated more topics as important than did experienced mothers.
      Individual teaching was rated most effective by both groups. Classroom teaching
      and the use of audiovisual media were considered less effective. CONCLUSIONS:
      This study supports postpartum education that focuses on the physical needs of
      mothers and infants, as well as individual teaching models. The special learning
      needs of new mothers, including those who are not married, must be considered.

PMID- 9549702
TI  - Mother-infant interaction and breastfeeding outcome 6 weeks after birth.
AB  - OBJECTIVE: This study explored the relationship of early postpartum maternal
      infant interactions to breastfeeding outcome at 6 weeks postpartum. DESIGN:
      Prospective, comparative descriptive study. SETTING: Women, Infants, and Children
      Supplemental Nutrition Program and Comprehensive Perinatal Services Programs in
      northern California. PARTICIPANTS: Forty-two Latina participants were recruited
      in the 3rd trimester of pregnancy. Eligibility criteria included age 18 years or
      older, primiparous at recruitment, antepartum desire to breastfeed 8 weeks or
      longer postpartum, planned hospital birth, full-term vaginal birth of a healthy
      newborn, and an uncomplicated, immediate postpartum course for mother and
      newborn, including being discharged together. MAIN OUTCOME MEASURES: The study
      examined breastfeeding dyads' early postpartum scores on Barnard's Nursing Child
      Assessment Feeding Scale (NCAFS) in relation to breastfeeding outcome 6 weeks
      postpartum. NCAFS tests were performed 28-90 hours postpartum in the
      participants' homes, and breastfeeding status was assessed by phone contact 6
      weeks postpartum. RESULTS: Dyads continuing to breastfeed at 6 weeks postpartum
      had significantly higher early postpartum NCAFS scores than did dyads who had
      weaned from the breast by 6 weeks postpartum. CONCLUSIONS: Optimal maternal
      infant interactions, as evidenced by higher scores on Barnard's NCAFS, were
      related to longer breastfeeding duration. Lower scores on the NCAFS, suggesting
      difficulties in maternal-infant interaction, were related to weaning earlier than
      planned.

PMID- 9549703
TI  - Attitudes and practices of registered nurses toward women who have experienced
      abuse/domestic violence.
AB  - OBJECTIVE: To compare the education, attitudes, and practices related to domestic
      violence of perinatal nurses from three types of practice sites. DESIGN: A
      descriptive study of responses to a questionnaire administered to a convenience
      sample and through a mailing. SETTING: Education conferences and responses to a
      mailing. PARTICIPANTS: Two hundred seventy-five nurses in perinatal practice (87
      public health, 71 hospital, 117 private office). MAIN OUTCOME MEASURES: Primary
      outcomes were attitudes and beliefs about domestic violence and nursing behavior
      when domestic violence was identified. The effects of education about domestic
      violence on practice and the effect of a personal/family history of domestic
      violence on practice were examined. RESULTS: Some differences were found in the
      attitudes and beliefs of nurses from different practice sites, but more
      differences were found in their behaviors. Only 54% of the total sample reported
      having education about domestic violence, received in formal or continuing
      education programs. Public health nurses were the most likely to have such
      education. Education affected both attitudes and behavior. In the total sample,
      31% of nurses reported abuse of themselves or family members. CONCLUSIONS:
      Nursing care for women who have experienced domestic violence includes assessment
      and appropriate counseling. Many nurses in this study lacked education about
      domestic violence. The provision of education about abuse and domestic violence
      is a first step toward a change in nursing practice.

PMID- 9549704
TI  - Pregnancy after perinatal loss: the relationship between anxiety and prenatal
      attachment.
AB  - OBJECTIVE: To determine the difference between levels of pregnancy-specific
      anxiety and prenatal attachment in a group of pregnant women who previously had a
      late pregnancy loss and a group of primiparous women of similar gestational age.
      To also determine the relationship, if any, between anxiety and prenatal
      attachment in both groups. DESIGN: A nonrandom, comparative descriptive design.
      SETTING: Participants recruited from medical offices, childbirth classes, and
      perinatal support groups and newsletters. PARTICIPANTS: A convenience sample of
      31 expectant mothers (15 primiparae and 16 who previously experienced a late
      pregnancy miscarriage, stillbirth, or neonatal death). Both groups of women were
      in the 2nd or 3rd trimester of their current pregnancy. MAIN OUTCOME MEASURES:
      Anxiety was measured using the Pregnancy Outcome Questionnaire; prenatal
      attachment was measured using the Prenatal Attachment Inventory. RESULTS: The
      loss group showed significantly greater levels of anxiety and significantly lower
      levels of prenatal attachment compared with a group of primiparous women of a
      similar gestational age. CONCLUSIONS: Women who experienced a previous late
      pregnancy loss had a higher level of anxiety related to concerns about the
      pregnancy and decreased prenatal attachment with the child in the current
      pregnancy. Women in their first pregnancy had decreased anxiety compared with the
      loss group. Higher levels of prenatal attachment also were shown in the
      primiparous group.

PMID- 9549705
TI  - Childbearing in Malawi, Africa.
AB  - Malawi is a small, landlocked country in South Eastern Africa that faces many
      challenges in providing health care to childbearing women. Through a partnership
      between the faculty of the University of Pennsylvania, School of Nursing, faculty
      of the Kamuzu College of Nursing in Malawi, and the Malawi Ministry of Health and
      Population, an ongoing collaboration has led to research and demonstration
      projects designed to improve the health of women and children in Malawi. To
      underscore the cultural context within which childbearing occurs, care of the
      childbearing family in Malawi is described, as is research that has documented
      some of the similarities and differences between childbearing in Malawi and the
      United States.

PMID- 9549706
TI  - Developing a research mentoring partnership in Israel.
AB  - A relationship begun in 1985 between the University of Pennsylvania School of
      Nursing and the Henrietta Szold Hadassah/Hebrew University has included a student
      exchange program and a faculty mentoring partnership. The student exchange
      focused on maternal-child nursing and led to the development of the faculty
      mentoring program. The goals of the latter program are to increase the expertise
      of the Israeli nursing faculty in the development of grant applications,
      publications, and abstracts and to develop a National Institutes of Health
      supported research project with an Israeli nursing faculty as principal
      investigator.

PMID- 9549707
TI  - Nursing in the newly independent states of the former Soviet Union: an
      international partnership for nursing development.

PMID- 9549708
TI  - An effort to upgrade perinatal nursing practice in Albania.
AB  - In 1994 the Jacobi Medical Center in Bronx, New York, and the University Hospital
      in Tirana, Albania, entered into a partnership designed to upgrade certain
      aspects of the health care system in Albania. During a 2-week trip, an American
      contingent of nurses and nurse-midwives worked to increase the knowledge base of
      Albanian nurses about some of the most important issues in perinatal care and of
      the roles of nurses and nurse-midwives in the United States as patient advocates
      and educators.

PMID- 9549709
TI  - Functional ability perceived by individuals following total knee arthroplasty
      compared to age-matched individuals without knee disability.
AB  - A comparison of function of individuals 1 year after total knee arthroplasty
      (TKA) with healthy control subjects (controls) meaningfully describes outcome in
      these patients. Perception of function measured by two questionnaires, the Lower
      Extremity Activity Profile (LEAP) and the Western Ontario McMaster Osteoarthritis
      Index (WOMAC), and walking and stair performance was compared between 29
      patients, 1 year after TKA, and 40 controls. There was significantly greater
      perceived difficulty with function in patients with TKA than in controls. In TKA
      men, LEAP and WOMAC scores correlated respectively with self-paced walk speed (r
      = -.71 and -.55) and stair performance time (r = 0.70 and 0.68). In TKA women,
      LEAP difficulty score correlated with self-paced walk speed (r = -.41) and stair
      performance time (r = -0.71). By 1 year, TKA subjects regained 80% of the
      function of controls. Perception of function after TKA can be measured by either
      questionnaire in men; however, the LEAP is the preferable questionnaire with
      women.

PMID- 9549710
TI  - Effect of coordination training on proprioception of the functionally unstable
      ankle.
AB  - Exercises to improve joint proprioception and coordination of the functionally
      unstable ankle are advocated throughout the literature, yet there is little
      evidence that these exercise have any effect on proprioception and balance. The
      purpose of this study was to determine the effects of a 6-week coordination and
      balance training program on proprioception of subjects with functional ankle
      instability. Forty-five subjects (age = 22.53 +/- 3.95 years, height = 172.04 +/-
      10.0 cm, weight = 71.72 +/- 15.7 kg) were randomly placed into a control (Group
      1), sham (Group 2), or experimental (Group 3) group. The experimental group
      trained 3 days per week, 10 minutes each day, performing various balance and
      proprioception exercises. Postural sway and active and passive joint position
      sense were assessed. Analysis of variance for postural sway modified equilibrium
      score for anterior and posterior sway, as well as medial and lateral sway
      revealed significant four-way interactions. Tukey post hoc analyses revealed that
      Group 3 performed significantly better (p < .05) than Group 1 and Group 2 on the
      posttests. There were no significant differences for joint position sense or
      postural sway index. Results suggest that balance and coordination training can
      improve some measures of postural sway. It is still unclear if joint position
      sense can be improved in the functionally unstable ankle.

PMID- 9549711
TI  - Clinical tests for ankle syndesmosis injury: reliability and prediction of return
      to function.
AB  - Despite the severity of ankle syndesmosis injuries, it has been argued that they
      are relatively poorly detected. This study investigated the interrater
      reliability of four orthopaedic tests for ankle syndesmosis injury and assessed
      their ability to predict the extended recovery times that have been reported as a
      consequence of this injury. Nine physiotherapists, working in random pairings,
      examined 53 subjects, all receiving treatment for ankle injury at two private
      clinics. Each subject was tested by two physiotherapists who independently
      performed the palpation test, external rotation test, squeeze test, and
      dorsiflexion-compression test. Kappa coefficient testing indicated that the
      external rotation test had the best interrater reliability (kappa = 0.75). The
      squeeze test was found to have moderate reliability (kappa = 0.50), and the
      palpation and dorsiflexion-compression tests both had only fair reliability
      (kappa = 0.36). The degree of pair-wise association between the results of the
      four tests was low (phi < or = 0.30 for all test combinations), suggesting that
      if all four tests were performed on the same subject, it was not likely that they
      would achieve similar results. Follow-up interviews were conducted to determine
      the time taken for subjects to walk 10 m without pain and, for sports injuries,
      the time taken to return to training and then to competition. For each test, Mann
      Whitney U values showed no significant difference between the recovery times of
      subjects with positive or negative test results, although subjects with recovery
      times markedly longer than normal were detected by three of the four tests. When
      an either/or combination of the external rotation and dorsiflexion-compression
      tests was considered, subjects with a positive test result took significantly
      longer to return to playing sports.

PMID- 9549712
TI  - Reliability and validity of rigid lift and pelvic leveling device method in
      assessing functional leg length inequality.
AB  - Clinicians commonly include an assessment of leg length inequality (LLI) as a
      component of a musculoskeletal examination. Little research is available,
      however, documenting reliability and validity of clinical methods for assessing
      LLI. The purpose of this study was to determine the reliability and validity of
      assessing functional LLI using a pelvic leveling device. Subjects were 19 women
      and 13 men between the ages of 18 and 55 who reported having a diagnosed or
      suspected LLI. Clinical determination of LLI was made by placing rigid lifts
      under the suspected shorter lower extremity until the leveling device indicated
      that the iliac crests were level. This measurement was made twice by one
      investigator and once by a second investigator. Standing radiographic
      measurements of LLI using rigid lifts were used to establish validity of the
      clinical method. Intraclass correlation coefficients [ICC(2,1)] and absolute
      difference values were computed to assess reliability and validity. The mean
      absolute difference between the two clinical measurements of LLI by the same
      investigator was 0.29 cm (+/- 0.52), with an ICC = 0.84. The mean absolute
      difference between clinical measurements of LLI by the two investigators was 0.49
      cm (+/- 0.46), with an ICC = 0.77. The ICC and mean absolute difference
      reflecting agreement between radiographic measurements and clinical measurements
      of LLI was 0.64 and 0.58 cm (+/- 0.58), respectively, for one investigator and
      0.76 and 0.55 cm (+/- 0.37), respectively, for the second investigator. The
      intratester reliability, intertester reliability, and validity assessments
      included instances in which paired observations disagreed regarding which lower
      extremity was the shorter lower extremity. Factors that may be associated with
      the unacceptable reliability and validity of the clinical assessment method
      include asymmetric positioning of the ilia, body composition of the patient, and
      design of the clinical instrument. The authors discuss clinical implications
      related to assessment of LLI.

PMID- 9549713
TI  - The effect of static stretch and dynamic range of motion training on the
      flexibility of the hamstring muscles.
AB  - To date, limited information exists describing a relatively new stretching
      technique, dynamic range of motion (DROM). The purpose of this study was to
      compare the effects of DROM with static stretch on hamstring flexibility. Fifty
      eight subjects, ranging in age from 21 to 41 years and with limited hamstring
      flexibility (defined as 30 degrees loss of knee extension measured with the femur
      held at 90 degrees of hip flexion), were randomly assigned to one of three
      groups. One group performed DROM 5 days a week by lying supine with the hip held
      in 90 degrees of flexion. The subject then actively moved the leg into knee
      extension (5 seconds), held the leg in end range knee extension for 5 seconds,
      and then slowly lowered the leg to the initial position (5 seconds). These
      movements were performed six times per session (30 seconds of total actual
      stretching time). The second group performed one 30-second static stretch, 5 days
      per week. The third group served as a control group and did not stretch. Before
      and after 6 weeks of training, flexibility of the hamstring muscles was
      determined in all three groups by measuring knee extension range of motion (ROM)
      with the femur maintained in 90 degrees of hip flexion. Data were analyzed with a
      2 x 3 (test x group) two-way analysis of variance (ANOVA) with repeated measures
      on one variable (test) and appropriate post hoc analyses. The results of the two
      way ANOVA revealed a significant interaction. Further statistical post hoc
      analysis of data to interpret the interaction revealed significant differences
      between the control group (gain = 0.70 degree) and both stretching groups, as
      well as a significant difference between the static stretch group (gain = 11.42
      degrees) and the DROM group (gain = 4.26 degrees). The results of this study
      suggest that, although both static stretch and DROM will increase hamstring
      flexibility, a 30-second static stretch was more effective than the newer
      technique, DROM, for enhancing flexibility. Given the fact that a 30-second
      static stretch increased ROM more than two times that of DROM, the use of DROM to
      increase flexibility of muscle must be questioned.

PMID- 9549714
TI  - Intramuscular temperature responses in the human leg to two forms of cryotherapy:
      ice massage and ice bag.
AB  - Cryotherapy is often used to affect the muscle underlying skin and subcutaneous
      tissues. However, the relationship between the penetrative ability of various
      cryotherapy methods and treatment time is not thoroughly understood. The purpose
      of this study was to measure muscle temperature responses during two frequently
      used cryotherapy techniques. A 23-gauge hypodermic needle microprobe was inserted
      to one-half skin-fold thickness plus 1 cm into the medial aspect of the
      gastrocnemius muscle of 14 subjects. Two groups of seven subjects each were
      measured for temperature changes during ice bag or ice massage treatment. Each
      treatment consisted of a 15-minute application of the selected method. A
      significant difference between the two methods was observed (t = -2,157, p < or =
      0.05). Ice massage achieved its lowest temperature in an average of 17.9 +/- 2.4
      minutes, while ice bag reached its lowest temperature in 28.2 +/- 12.5 minutes.
      Ice massage appears to cool muscle more rapidly than ice bag.

PMID- 9549715
TI  - Differential diagnosis of the hip vs. lumbar spine: five case reports.
AB  - With recent health care policy changes and the implementation of direct access in
      many states, physical therapists must be able to identify pathology that is
      beyond their scope of practice. The five case reports presented in this series
      required the differential diagnosis of hip vs. lumbar spine pathology. All of the
      cases required a referral from the physical therapist to either the patient's
      physician or a specialist because of abnormal screening test results. Each
      referral resulted in a new diagnosis of pathology that was beyond the scope of
      physical therapy. Cyriax's concepts of capsular and noncapsular patterns of joint
      restriction and the "Sign of the Buttock" proved useful in differentiating
      between hip and lumbar spine pathology in each patient. Our clinical experience
      indicates that utilizing the presence/absence of a capsular pattern and a "Sign
      of the Buttock" to screen out hip pathology in patients may be effective;
      however, further research is needed to support these claims.

PMID- 9549716
TI  - [Long-term strategy for the management of Parkinson patients].

PMID- 9549717
TI  - [Current strategies in the therapy of epilepsy].

PMID- 9549718
TI  - Status of risk factors for vascular dementia.
AB  - The two most common causes of vascular dementia (VAD) are dementia evolving in
      connection with multiple small or large strokes and dementia related to ischemic
      white-matter lesions (WMLs) of the brain. The knowledge about risk factors for
      these disorders is still scarce. Besides sharing risk factors with stroke,
      dementia with multiple small or large brain infarcts is also associated with non
      vascular risk factors such as high alcohol consumption, psychological stress in
      early life, lower formal education, blue collar occupation, and occupational
      exposures. Risk factors for dementia in stroke victims include stroke-related and
      non-stroke related risk factors. Non-stroke-related factors are similar to those
      found in Alzheimer's disease. The main risk factors for ischemic WMLs are
      hypertension or increased blood pressure, but WMLs have also been associated with
      a number of other vascular risk factors. In recent years, Alzheimer's disease
      (AD) has also been reported to be associated with vascular risk factors,
      including hypertension, coronary heart disease, atrial fibrillation, diabetes
      mellitus, and WMLs. Although these associations may reflect an overdiagnosis of
      AD in cases with silent cerebrovascular disease, or that cerebrovascular disease
      increases the possibility that individuals with Alzheimer lesions will express a
      dementia syndrome, there are also alternative explanations. AD and
      cerebrovascular disease may for instance share similar risk factors or etiologic
      pathways. The pathogenetic implications for the association between AD and
      vascular factors need to be further explored. There is also a need for more
      studies on risk factors for VAD and risk factors for dementia in stroke samples,
      as well as studies on non-vascular risk factors for ischemic WMLs.

PMID- 9549719
TI  - Status of treatment of vascular dementia.
AB  - The therapeutic goal in treating vascular dementia has been based on its presumed
      association with cerebral arteriosclerosis. Therefore, it is necessary to control
      risk factors for arteriosclerosis. In this connection, application of platelet
      aggregating substances has been used extensively. Promising results have also
      been observed by altering the hemorheologic profile because hemorheologically
      active substances may be able to ameliorate the course of vascular dementia.
      Further improvement could be achieved by application of the HELP system to
      enhance the effect of hemorheologically active drugs. Using the HELP system, LDL,
      cholesterol, triglycerides and fibrinogen can be lowered considerably and may
      result in clinical improvement or slowing of the progression of vascular
      dementia.

PMID- 9549720
TI  - Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's
      disease.
AB  - The epsilon 4 allele of the apolipoprotein E (apoE) is associated with
      Alzheimer's disease (AD) and also with elevated serum total cholesterol and low
      density lipoprotein levels. However, the interrelationships between apoE
      genotype, plasma cholesterol levels and AD risk have been studied very little. We
      examined the possible role of serum total cholesterol in the pathogenesis of AD
      in a population-based sample of 444 men, aged 70-89 years, who were survivors of
      the Finnish cohorts of the Seven Countries Study. Previous high serum cholesterol
      level (mean level > or = 6.5 mmol/l) was a significant predictor of the
      prevalence of AD (odds ratio = 3.1; 95% confidence interval = 1.2, 8.5) after
      controlling for age and the presence of apoE epsilon 4 allele. In men who
      subsequently developed AD the cholesterol level decreased before the clinical
      manifestations of AD. We conclude that high serum total cholesterol may be an
      independent risk factor for AD and some of the effect of the apoE epsilon 4
      allele on risk of AD might be mediated through high serum cholesterol.

PMID- 9549721
TI  - Disposition after acute stroke: who is not sent home from hospital?
AB  - BACKGROUND: Known demographic and clinical characteristics of stroke survivors
      that affect selection of the facility to which they are discharged after
      hospitalization for an acute stroke are, for the most part, not population based
      and therefore may be unrepresentative. We present an analysis of such
      characteristics using the Lehigh Valley stroke cohort which is population based.
      METHOD: We enrolled patients within 1 month of onset of their initial acute
      stroke who were hospitalized between 1987 and 1989 at one of the eight hospitals
      in the Lehigh Valley, and 662 patients were discharged alive. The facility to
      which they were discharged was known for 660. Data on age, sex, presence of five
      selected comorbidities (hypertension, myocardial infarction, cardiac arrhythmia,
      diabetes mellitus and transient ischemic attacks), length of hospitalization and
      neurologic deficits from the stroke were systematically collected on standardized
      forms. Polytomous logistic regression was used to determine the factors
      associated with not being discharged home. Relative risk (RR) associated with
      discharge to a nursing or rehabilitation facility for each independent predictor
      was calculated using as the referent, those who went home. RESULTS: Older age was
      a statistically significant predictor of not being sent home (RR = 1.2 for
      nursing home placement), but gender and living with a spouse were not. Having a
      selected comorbidity did not increase the RR of not being sent home regardless of
      the type, nor did risk of not being sent home increase with more than one
      illness. Considering neurologic deficits from the stroke, patients with lower
      extremity weakness had a 2.6- and 3.5-fold risk of being sent to a nursing or a
      rehabilitation facility, respectively, compared to those without such weakness
      while for those with upper extremity weakness, the RR was 1.5 and 4.9,
      respectively. Language deficit imposed a RR of 3.1 and 2.3 of going to a nursing
      or rehabilitation facility, respectively. Right facial weakness also emerged as a
      significant risk factor for not being discharged home, perhaps because of its
      association with language deficit. The longer a patient was hospitalized after a
      stroke, the less likely it was that such a patient would go home (RR =
      1.1/hospitalization day). CONCLUSION: Using population-based data on stroke
      survivors, our study showed the characteristics of patients who are less likely
      to be discharged home and, instead, are discharged to a nursing or a
      rehabilitation facility. Data like ours which were population based may be useful
      in discharge planning for stroke patients by policy makers and health care
      providers.

PMID- 9549722
TI  - Hospital-based diabetic neuropathy: prevalence in eastern Black Sea region of
      Turkey.

PMID- 9549723
TI  - Analysis of the PTEN gene in human meningiomas.
AB  - Previous observations demonstrated that the neurofibromatosis type 2 gene (NF2)
      plays an important role in the pathogenesis of the transitional, fibroblastic and
      malignant variants of human meningiomas. No specific genes have been associated
      with the pathogenesis of meningothelial meningiomas and with the progression to
      anaplastic meningiomas. However, allelic losses on chromosomal arms 1p, 10q and
      14q have been implicated in the process of malignant progression. Recently, PTEN
      (phosphatase and tensin homolog deleted on chromosome ten) also termed MMAC1
      (mutated in multiple advanced cancers 1) or TEP1 (TGF--regulated and epithelial
      cell-enriched phosphatase), emerged as a candidate gene on chromosome 10q23.3.
      Initial studies revealed mutations of PTEN in limited series of glioblastomas,
      breast, kidney and prostate carcinomas mainly as cell lines. In order to evaluate
      the involvement of PTEN in the development of meningiomas, we have analysed the
      entire coding sequence of the gene in a series of 55 meningiomas (WHO grade I).
      10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade
      III). No PTEN mutations were seen in the WHO grade I meningiomas. However, one of
      the anaplastic meningiomas carried a somatic mutation. In addition, all tumours
      were examined for the presence of homozygous deletions of PTEN but these were not
      detected in any of the meningiomas. Our data suggest that mutations in PTEN are
      not involved in the formation of low grade meningiomas, but may contribute to
      malignant progression in a fraction of anaplastic meningiomas.

PMID- 9549724
TI  - gp130RB13-6-positive neural progenitor cells are susceptible to the oncogenic
      effect of ethylnitrosourea in pre-natal rat brain.
AB  - Proliferation-competent rat brain precursor cells of glial lineages are thought
      to preferentially undergo malignant transformation after transplacental exposure
      to ethylnitrosourea (EtNU). We recently have reported that monoclonal antibody
      (mAb) RB13-6 recognizes a developmentally regulated 130 kDa cell surface
      glycoprotein (gp130RB13-6) transiently expressed by a small subpopulation of
      glial progenitor cells in pre-natal rat brain. The expression of gp130RB13-6 has
      now been analysed immunocytochemically in malignant gliomas induced on day 15, 18
      or 21 of gestation and in long-term cultures of fetal brain cells (FBC) isolated
      after in vivo-exposure to EtNU on day 18 of gestation. Malignant gliomas induced
      at different gestational stages contained varying proportions of gp130RB13-6
      positive cells, whereas a subpopulation of proliferative neural progenitor cells
      exhibiting sustained gp130RB13-6 expression persisted in long-term FBC cultures
      after 3 months. This subpopulation, which was not selected for in control
      cultures of FBC derived from buffer-treated rats, gave rise to malignant cell
      lines after a period of time similar to the latency period required for glioma
      development in vivo. These data suggest that gp130RB13-6-positive cells of the
      immature rat nervous system may represent a subset of neural progenitor cells
      particularly susceptible to the oncogenic effect of EtNU.

PMID- 9549725
TI  - Proliferation and cell death in oligodendrogliomas.
AB  - The rates of cell proliferation and of cell loss influence the growth rate of a
      tumour and reflect genetic changes. We studied proliferation and apoptosis in
      oligodendrogliomas and their relationship to progression of the tumours. Thirty
      two cases of oligodendroglioma were retrieved spanning a 10-year period. The
      diagnosis and grade were reviewed and follow-up data obtained. Mitotic index (MI)
      and apoptotic index (AI) were determined from haematoxylin and eosin (H & E)
      stained sections. A labelling index (LI) of proliferating cells was obtained
      using the MIB1 antibody to the Ki-67 antigen. A further index of apoptosis was
      obtained using in situ end-labelling of DNA strand breaks (TUNEL index, TI).
      Fourteen cases were graded as II, 18 as III (1993 WHO). LI was significantly
      higher in grade III than in grade II tumours (P < 0.01) but the difference in
      apoptotic indices between grades was not significant. There was a significant (P
      = 0.036) positive correlation between the logarithms of TI and LI. Construction
      of survival curves demonstrated a significant difference in survival according to
      histological grade (P < 0.05). Stratification of cases by LI alone did not
      predict significantly different survival outcomes, and apoptotic indices did not
      demonstrate a relationship to survival. A positive relationship was demonstrated
      between proliferation and apoptosis in oligodendrogliomas. The levels of
      apoptosis observed indicate that this phenomenon may have an important influence
      on the overall rate of tumour growth.

PMID- 9549726
TI  - Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the
      vasculature of oligodendrogliomas.
AB  - Vascular endothelial growth factor (VEGF) appears to be implicated in tumour
      angiogenesis. In the present study immunohistochemical expression of VEGF was
      evaluated in 34 oligodendrogliomas (13 grade II, 21 grade III [WHO]). VEGF
      immunoreactivity was found in 31 of 34 cases. Expression of VEGF was observed in
      endothelial cells and some vascular smooth muscle cells, but not in neoplastic
      oligodendrocytes. Vessel counts, percentages of VEGF-positive vessels and vessels
      with vascular endothelial proliferation were assessed. The degree of VEGF
      labelling and vascular-endothelial proliferation in each vessel were evaluated
      using a 3 degree intensity score. Expression of VEGF was higher in grade III than
      in grade II oligodendrogliomas as assessed by percentage of VEGF positive vessels
      (55.8 +/- 29.2% vs 17.0 +/- 19.0% [P < 0.001]) and by VEGF immunostaining
      intensity (1.90 +/- 0.60 vs 0.90 +/- 0.40 [P < 0.001]). VEGF expression did not
      correlate with vessel density. Intensity of VEGF expression correlated positively
      with that of vascular-endothelial proliferation in grade III tumours (r = +0.47
      [P < 0.05]). The percentage of VEGF positive vessels showed some degree of
      positive correlation with the percentage of vessels showing vascular-endothelial
      proliferation (r = +408 [P < 0.10]). Within individual grade III tumours 67.5 +/-
      29.6% of all vessels with vascular-endothelial proliferation were VEGF-positive
      and 31.0 +/- 20.5% of all VEGF-positive vessels showed no evidence of vascular
      endothelial proliferation. We conclude that (i) expression of VEGF is observed in
      the vasculature of oligodendrogliomas; (ii) marked expression of VEGF is observed
      in grade III oligodendrogliomas; (iii) VEGF may be one of the interrelated
      causative stimuli acting in concert to induce vascular-endothelial proliferation.

PMID- 9549727
TI  - Degeneration of the cerebellar granule cell layer in transgenic mice expressing
      genes of human foamy virus.
AB  - Transgenic mice expressing various combinations of structural and regulatory
      genes of human foamy virus (HFV) develop a neurodegenerative syndrome. delta gpe
      transgenic mice (which express the auxiliary bel-1 and bet genes along with
      truncated forms of gag, pol, and env) develop a severe neurological syndrome
      consisting mainly of spastic tetraparesis and blindness, and show neuronal loss
      in the hippocampus and cerebral cortex. In addition, mice in two of eight delta
      gpe lines developed an ataxic gait. Here we studied the phenotype of these two
      lines, and show that these mice exhibit progressive degeneration of their
      cerebellar granule cells beginning at 4-8 weeks of age. Transgenic mRNA and HFV
      proteins accumulate in cerebellar granule cells immediately before the onset of
      degeneration. The Purkinje cell layer is largely unaffected by this pathological
      process. Probably due to the loss of granule cell processes, the cerebellar
      molecular layer is narrowed in the late stages of the disease. These findings
      indicate that HFV gene products can be neurotoxic for cerebellar granule cells.

PMID- 9549728
TI  - Fractionator analysis shows loss of neurons in the lateral geniculate nucleus of
      macaques infected with neurovirulent simian immunodeficiency virus.
AB  - Infection of macaques with neurovirulent strains of simian immunodeficiency virus
      (SIVmac) is an experimental model for the neurological manifestations of AIDS.
      Loss of neurons has been reported in the cerebral cortex following
      immunodeficiency viral infection, but thalamic structures which may contribute to
      electrophysiological changes and neurological deficits have not been examined. In
      this study, the lateral geniculate nucleus (LGN) of macaques inoculated with
      macrophage-tropic, neurovirulent virus SIVmac239 (R71 and 17E) was examined for
      neuron loss using the optical fractionator method. Estimates of the number of
      neurons in the P layers of the lateral geniculate nucleus of age-matched control
      macaques ranged from 1.0 to 1.3 x 10(6), while the number of neurons in SIV
      infected macaques ranged from 0.8 to 1.1 x 10(6), reflecting neuron loss of up to
      28%. Neuron loss was not observed in the magnocellular layer. The total number of
      glia and glial density were unchanged. Loss of neurons in the lateral geniculate
      nucleus was correlated with the pattern of neuropathological changes. Neuron loss
      was most severe in animals with encephalitis concentrated in the brain stem and
      subcortical white matter and was less apparent in animals with diffuse
      encephalitis. Neuron loss in the lateral geniculate nucleus did not explain
      changes observed in the visual evoked potential, which was severely affected in
      two animals which showed a loss of 24 and 26%, while it was normal in a third
      animal which showed neuron loss of 28%.

PMID- 9549729
TI  - Argyrophilic grains of Braak: occurrence in dendrites of neurons containing
      hyperphosphorylated tau protein.
AB  - Braak's argyrophilic grains (ArGs) are spindle-shaped neuropil structures
      originally found in patients afflicted with adult onset dementia. We recently
      observed that tau protein is hyperphosphorylated in most nerve cells in areas
      rich in ArGs, suggesting that these grains may be a morphological expression of
      tau protein pathology in local neurons. The aim of this study was therefore to
      determine in three cases with ArGs whether grains are associated with individual
      neurons containing hyperphosphorylated tau. A combination of Gallyas silver
      staining and AT8 immunocytochemistry was used. AT8 is a monoclonal antibody that
      recognizes tau in a phosphorylation-dependent manner. Up to 80% of pyramidal
      cells of sector CA1 showed diffuse AT8 staining of their cell bodies and
      dendrites. Most grains were freely scattered throughout the neuropil. However,
      some were clearly located in side-branches of apical dendrites of AT8
      immunoreactive pyramidal neurons. Dendritic branches often formed bush-like
      ramifications containing clusters of ArGs. Other dendrites consisted of a single
      stump containing one or two large grains at their tips. Spheroidal enlargements
      of dendritic branches, with a size corresponding to ArGs, were also found in
      Golgi Cox preparations of cases with ArGs but not in Alzheimer's disease cases or
      in controls. Our results show that some ArGs are formed within dendrites of
      neurons whose most obvious pathology is a diffuse hyperphosphorylation of the tau
      protein. Furthermore, morphology of dendrites containing grains suggests that a
      process of progressive shrinkage of dendrites is taking place in neurons bearing
      ArGs.

PMID- 9549730
TI  - Endothelial changes in muscle and skin biopsies in patients with CADASIL.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is characterized by the deposition of granular
      osmiophilic material in association with vascular smooth muscle cells in many
      different organs. However, the cause of the subsequent destruction of smooth
      muscle cells that are surrounded by granular osmiophilic material is unclear. In
      the present study, the ultrastructural changes that occur in endothelial cells in
      CADASIL have been evaluated by examining blood vessels in six skin biopsies and
      seven muscle biopsies belonging to three different CADASIL pedigrees. The
      appearances have been compared with five skin biopsies and five muscle biopsies
      from age-matched controls without vascular disease. The most striking features
      observed in vessels in the skin of CADASIL patients were attenuation of
      endothelial cells and increased density of endothelial cytoplasm, accompanied by
      the presence of compact bundles of microfilaments within the cytoplasm of
      endothelial cells. Endothelial cells in muscle biopsies from CADASIL patients, on
      the other hand, were swollen until destruction of tight junctions were observed.
      These findings suggest that impaired permeability of vascular endothelium may
      play a role in the destruction of vascular smooth muscle cells in CADASIL.
      Furthermore, the results of this study suggest that further fine structural
      investigation of blood vessel endothelium and underlying smooth muscle may lead
      to a better understanding of the pathophysiology of CADASIL.

PMID- 9549731
TI  - Differential labelling of laminin alpha 2 in muscle and neural tissue of dy/dy
      mice: are there isoforms of the laminin alpha 2 chain?
AB  - Laminin alpha 2, a sub-unit of the basement membrane component laminin-2, is
      deficient in the dy/dy and allelic dy2 J/dy2 J mouse. It is also the defective
      protein in a proportion of children with congenital muscular dystrophy. Linkage
      and mutational analysis have established that this is a primary effect caused by
      defects in the LAMA2 gene. Laminin alpha 2 has previously been shown to be
      deficient in dy/dy skeletal muscle, peripheral nervous system and brain. We
      report here preliminary observations on differences in detection of laminin alpha
      2 in muscle, peripheral nerves and brain of dy/dy mice using three, well
      characterized antibodies. In normal muscle laminin alpha 2 is localized to the
      basement membrane of the myofibres and the Schwann cells of peripheral nerves,
      whilst in adult brain it is only detected on blood vessels. Our results show that
      there is appreciable, but slightly reduced, expression of laminin alpha 2 in
      skeletal muscle of dy/dy mice but almost no detectable protein in the brain,
      peripheral nerve and spinal nerve roots. Our observations are at present
      unexplained but they raise the possibility for the first time that there may be
      different tissue specific isoforms of laminin alpha 2. Molecular characterization
      of possible differences responsible for our observations may aid the
      identification of the mutation in the dy/dy mouse and lead to a better
      understanding of the role and expression of laminin alpha 2 in pathological
      conditions.

PMID- 9549733
TI  - Gastro-oesophageal reflux: theory over experience?

PMID- 9549732
TI  - Local expression of cytokines in idiopathic inflammatory myopathies.
AB  - The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM),
      polymyositis (PM), and inclusion body myositis (IBM), are regarded as autoimmune
      diseases. They are characterized by chronic lymphocytic and macrophagic
      infiltration in muscle tissue. Of particular importance in understanding the
      immune response to IIM is the specific pattern of locally produced cytokines.
      Frozen muscle tissues from IIM (5 DM, 3 PM, and 1 IBM) were used to investigate
      the cytokine responses. The RT-PCR technique was instrumental to determine the
      pattern of expression of pro-inflammatory (IL-1 beta, IL-6, TNF-alpha), Th1 (IFN
      gamma IL-2), and Th2 (IL-4) cytokines. Immunohistochemistry was also used to
      localize morphologically IFN-gamma and IL-4. Our results show that pro
      inflammatory cytokines and Th1 cytokines are mainly expressed in IIM. The
      accumulation of mononuclear inflammatory cells and the inflammatory syndrome in
      IIM are probably related in part to the production of pro-inflammatory cytokines.
      Moreover, the pattern of local cytokine expression is consistent with a Th1
      immune response related to autoimmune diseases.

PMID- 9549734
TI  - Chronic pain management in children. Part II: Reflex sympathetic dystrophy.

PMID- 9549735
TI  - Children who withdraw consent for elective surgery.
AB  - Parents and legal guardians have authority to consent to medical treatment on
      behalf of minors. Recently, the concept of emerging competence has been
      popularized, whereby a child may achieve sufficient understanding and maturity to
      enable him/her to make a wise choice in his/her own interests. Although there are
      undoubted merits in involving children in their medical treatment, the ultimate
      legal authority for consent rests with parents and guardians acting on the advice
      of doctors and in the child's best interests. We describe two cases in which
      children withdrew their consent to elective surgery, despite the help and
      encouragement of their parents and doctors. Surgery was cancelled rather than use
      force to induce anaesthesia. In practice, it seems that a child must demonstrate
      a greater maturity and understanding to refuse medical treatment than to agree to
      it. Some advice is given to clinicians facing similar situations.

PMID- 9549737
TI  - Early intravenous cannulation in children during inhalational induction of
      anaesthesia.
AB  - Intravenous cannulation is obtained in almost all patients scheduled for
      operative intervention under anaesthesia. In our practice, inhalational induction
      precedes cannulation in children in order to avoid pain and discomfort, and
      cannulation is delayed until the child is adequately anaesthetized in fear of
      precipitating laryngospasm due to painful stimulus of venepuncture in the light
      stage of anaesthesia. This study was performed on 150 patients between two to
      eight years of age to determine if there is a difference in the incidence of
      untoward incidents, if cannulation is performed when children are lightly
      anaesthetized (Early, Group E), as compared to when they are deeply anaesthetized
      (Late, Group L). In patients randomized to early cannulation, the results showed
      that there was a significantly shorter time from induction to venous cannulation,
      the halothane concentration was lower at the time of cannulation, there was a
      greater incidence of movement on cannulation and a greater incidence of changes
      in heart rate, blood pressure, and respiratory rate. There was no significant
      differences in the incidence of laryngospasm or in the success rate of
      intravenous cannulation between the two groups. We conclude that venous
      cannulation can be safely performed during the light stages of anaesthesia.

PMID- 9549736
TI  - Oral midazolam premedication and postoperative behaviour in children.
AB  - We examined the effect of oral midazolam premedication on postoperative
      behaviour. Seventy children (ASA Physical Status 1 and 2; aged 1-10 yrs) were
      assigned randomly in a prospective, blinded fashion to receive either midazolam
      0.5 mg.kg-1 (maximum 10 mg) or placebo. Behaviour assessments were made prior to
      medication, during induction of anaesthesia and 15 min following arrival to
      recovery room. The baseline behavioural evaluation scores were not significantly
      different. The children receiving midazolam cried significantly less during
      induction (P < or = 0.02). At one week follow-up, eight of 35 subjects receiving
      placebo had experienced adverse behaviour changes (nightmares, night terrors,
      food rejection, anxiety, negativism); 19 of 35 of the midazolam group experienced
      these changes (P < or = 0.02). At four week follow-up, most behaviour changes had
      resolved. Children given preoperative oral midazolam were less likely to cry and
      fight while being anaesthetized, and preoperative sedation was associated with
      increased incidence of adverse postoperative behaviour changes.

PMID- 9549738
TI  - Ropivacaine in paediatric surgery: preliminary results.
AB  - In a double blind study 40 patients, aged 1-9 years, undergoing elective minor
      surgery were examined and randomly divided in two groups (20 children each).
      After light general anaesthesia Group 1 received caudal injection of bupivacaine
      0.25% 2 mg.kg-1 while Group 2 received 0.2% ropivacaine 2 mg.kg-1. No differences
      were observed in demographic data, HR, BP and duration of surgery; the onset time
      of anaesthesia was 12 min and 9 min in Group 1 and 2 respectively. Ten patients
      in Group 1 received paracetamol in the first 24 h after surgery while only two
      children in Group 2 needed analgesic; even the duration of analgesia in the
      patients requiring paracetamol was superior in group 2 (520 min vs 253 min). No
      motor block was apparent at awakening in either group and no side effect was
      noticed. In conclusion ropivacaine seems to be an effective and safe drug in
      paediatric regional anaesthesia.

PMID- 9549740
TI  - Reference values of gastric intramucosal pH in children.
AB  - To determine the reference values of gastric intramucosal pH (pHi) by tonometry
      in paediatric patients, we studied 17 children (nine males, eight females) with
      no systemic or gastrointestinal disease, aged six months to 12 years undergoing
      minor reconstructive surgery. Following anaesthetic induction a sigmoid tonometry
      catheter was inserted (Tonometrics, Inc.) into the stomach of the patients under
      direct vision. All children were normoventilated and were haemodynamically
      stable. After an equilibration period of 30 min, gastric pHi was calculated by
      applying the Henderson-Hasselbalch equation on the PCO2 obtained with the
      tonometer and the bicarbonate from the arterial blood gas analysis. The mean
      gastric pHi in our patients was 7.35 +/- 0.06 (SD). The normal pHi in the general
      population is estimated to be 7.31-7.40, with a confidence interval of 99%. No
      correlation was found between pHi and arterial pH, bicarbonate or base excess.
      Under conditions of normal ventilation and haemodynamic stability, healthy
      children during general anaesthesia have gastric intramucosal values similar to
      those of adults.

PMID- 9549739
TI  - The advantages of intrathecal opioids for spinal fusion in children.
AB  - Two groups of 40 homogeneous patients (ASA physical status (1-2)) with idiopathic
      scoliosis undergoing spinal fusion with CD instrumentation were studied
      prospectively. Group A (intrathecal) received a mixture of morphine and
      sufentanil administered intrathecally at the level of L3-L4 after the induction
      of anaesthesia. Group B (control) had inhalation and intravenous narcotic
      anaesthesia. The use of intrathecal opioids resulted in a significant reduction
      of blood pressure without the use of any hypotensive agents and produced
      prolonged postoperative analgesia. There was no adverse effect on somatosensory
      evoked potentials. The dose requirement for the anaesthetic agents was
      significantly reduced and the blood loss was 27% of their blood volume compared
      with 53% in the control group. No long or short term impairment of cerebral or
      spinal function was observed. The use of intrathecal opioids supplemented with
      other anaesthetic agents is an alternative method with multiple benefits for any
      major surgery such as spinal fusion.

PMID- 9549741
TI  - The effect of circuit compliance on delivered ventilation with use of an adult
      circle system for time cycled volume controlled ventilation using an infant lung
      model.
AB  - This in vitro study examined the effect of circuit compliance on delivered
      ventilation (VE) using a time-cycled, volume controlled circle system in an
      infant lung model. A Bio-Tek ventilator tester set to simulate normal and
      abnormal lung compliance measured VE delivered by the Narkomed 2B system. Circle
      circuits of varied compliance (2.75, 1.22 and 0.73 microliters.cm H2O-1) were
      tested. Tidal volume was adjusted to peak inflation pressures (PIP) of 20, 30,
      40, and 50 cm H2O with three circuits, two lung compliances, and four different
      size tracheal tubes (TT) (2.5, 3.5, 4, 4.5 mm ID). Data were analysed using the
      multiple regression technique. Delivered VE was directly related to PIP and lung
      compliance. Delivered VE was not affected by the choice of circuit. TT size had
      minimal effects on VE when lung compliance was low; TT size was a more important
      factor when test lung compliance was normal. Extrapolating this data to the
      clinical setting, adequate ventilation of infants can be achieved with an adult
      circle system if an appropriate PIP is chosen, regardless of the compliance of
      the circuit used. Infants with poor lung compliance may require very high PIP for
      adequate ventilation.

PMID- 9549742
TI  - Transcutaneous CO2 tension effects of clonidine in paediatric caudal analgesia.
AB  - In adults, clonidine when added to bupivacaine, results in no detectable
      respiratory depressant effect except when carbon dioxide challenge is performed.
      However, to date no investigations have quantified this in children. Twenty-four
      children (nine months to seven years) were randomized in a double-blind study
      into two groups. After induction, a caudal block was performed with 1 ml.kg-1
      0.25% bupivacaine. Clonidine 1 microgram.kg-1 was added in the clonidine group,
      and 1 ml normal saline in the placebo group. Patients were monitored in the
      recovery room for three h from arrival to discharge with continuous pulse
      oximetry, respiratory rate, a transcutaneous CO2 tension (tcPCO2) every 15 min,
      and a four point sedation score every 30 min. Mean tcPCO2 and respiratory rate
      values were not different between the two groups. Apnoea and desaturation less
      than 97% were not observed. The sedation score decreased with time in both
      groups, and the score time interval was significantly higher in the clonidine
      group (P < 0.05). All the patients left the recovery room with a sedation score
      of 1, excepting four in the clonidine group with a sedation score of 2. Clonidine
      1 microgram.kg-1 with 0.25% bupivacaine mixture in caudal analgesia in children
      did not induce an increase in tcPCO2 despite prolonged sedation.

PMID- 9549743
TI  - Prophylactic therapy with granisetron in the prevention of vomiting after
      paediatric surgery. A randomized, double-blind comparison with droperidol and
      metoclopramide.
AB  - The antiemetic efficacy of droperidol, metoclopramide and granisetron was
      compared with placebo in the reduction of vomiting after paediatric surgery (the
      extremities; inguinal hernia; and phimosis) during general inhalational
      anaesthesia. One hundred children, ASA physical status I, 4-10 years of age, were
      enrolled in a prospectively, randomized, double-blind investigation and assigned
      to one of four treatment regimens: placebo (saline, n = 25), droperidol (50
      micrograms.kg1, n = 25), metoclopramide (0.25 mg.kg-1, n = 25) or granisetron (40
      micrograms.kg-1, n = 25). These drugs were administered intravenously (i.v.)
      after inhalation induction of anaesthesia. A complete response, defined as no
      emesis and no need for another rescue antiemetic during the first 24 h after
      anaesthesia, occurred in 60%, 76%, 68% and 88% of patients who had received
      placebo, droperidol, metoclopramide and granisetron, respectively (P < 0.05;
      overall Fisher's exact probability test). The incidence of adverse events
      postoperatively was not different among the treatment groups. In conclusion,
      granisetron 40 micrograms.kg-1 is a better antiemetic than droperidol and
      metoclopramide when compared to placebo for the prevention of postoperative
      emesis in children.

PMID- 9549744
TI  - Anaesthetic management of a patient with Plott's syndrome.
AB  - There are only seven reported cases of Plott's syndrome and no anaesthetic
      descriptions of this rare syndrome which is characterized by vocal cord
      paralysis, psychomotor retardation and sixth nerve palsy. The major anaesthetic
      implication is postoperative upper airway control. We describe the anaesthetic
      management of a 15-year-old boy who presented for magnetic resonance imaging
      [MRI] of his brain.

PMID- 9549745
TI  - Anaesthetic implications of Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome is a congenital disease characterized basically by
      psychomotor retardation associated with a series of malformations (mainly
      skeletal craniofacial deformities together with gastrointestinal and cardiac
      malformations). We present the case of a patient who underwent trauma surgery,
      discuss the anaesthetic problems involved and their relationship to the
      malformations that constitute this syndrome.

PMID- 9549746
TI  - Anaesthetic management of a prematurely born infant with Cantrell's pentalogy.
AB  - Cantrell's pentalogy (CP) is a rare congenital syndrome combining a defect of the
      supraumbilical abdominal wall, the agenesis of the lower part of the sternum and
      of the anterior portion of the diaphragm, the absence of the diaphragmatic part
      of the pericardium, and a cardiac malformation. It was first described by
      Cantrell in 1958 (1,2). We report the case of a prematurely born infant with CP
      and Wolff-Parkinson-White (WPW) syndrome who required surgery first for bilateral
      inguinal hernia repair and later for Blalock-Taussig shunt. During these two
      procedures, our anaesthetic plan was to preserve the fragile equilibrium of both
      the pulmonary and the cardiovascular systems.

PMID- 9549747
TI  - Sevoflurane for controlled hypotension during spinal surgery: preliminary
      experience in five adolescents.
AB  - The physical properties of sevoflurane suggest that it may be a suitable agent
      for controlled hypotension. With its low blood:gas partition coefficient of 0.69,
      it has a rapid onset of action making it easy to rapidly control blood pressure.
      The current report outlines preliminary experience with sevoflurane for
      controlled hypotension during posterior spinal fusion in five adolescents. The
      patients ranged in age from 12 to 16 years and in weight from 49 to to 72kg. The
      duration of controlled hypotension varied from two to three h. The expired
      sevoflurane concentration required to maintain the mean arterial pressure (MAP)
      at 55 to 65 mmHg varied from 2 to 4%. With sevoflurane, there was an increase in
      heart rate from baseline of 74 +/- 7 beats.min-1 to a maximum of 83 +/- 13
      beats.min-1 (P = 0.038). One patient required three intravenous doses of esmolol
      (10mg each) for a heart rate in excess of 100 beats.min-1. Estimated blood loss
      varied from 300 to 850 ml. No patient received homologous blood. No excessive
      hypotension was noted with sevoflurane. No patient required calcium, alpha
      adrenergic agonists, or ephedrine for excessive hypotension. When controlled
      hypotension was no longer necessary, the sevoflurane concentration was decreased
      to 1%. After decreasing the sevoflurane to 1%, the time to return of the MAP to
      baseline varied from 4 to 8 min (5.6 +/- 1.8 min).

PMID- 9549748
TI  - Twelve hours of gastric ventilation: a recipe for disaster (a suggested remedy).
AB  - A forty-three-day-old infant was intubated by the Neonatal Intensive Care Unit
      (NICU) staff. A nasogastric tube was in place for the duration. The patient's
      vital signs remained stable during 12 h of positive pressure ventilation. A
      Broviac catheter placement was scheduled in the NICU. The position of the
      tracheal tube (TT) was not verified prior to induction of anaesthesia. After the
      induction, the patient's condition deteriorated. The TT was found to be
      positioned within the oesophagus. A near catastrophe was successfully averted by
      discovering the malpositioned TT and replacing it with a properly positioned TT.
      We believe that had we clamped the existing nasogastric tube preoperatively, a
      noticeable abdominal distention would have occurred alerting us to a
      malpositioned TT. We suggest that clamping a preexisting nasogastric tube may
      have merit to alert one to a malpositioned TT.

PMID- 9549749
TI  - Anaesthetic management of a patient with Freeman Sheldon syndrome.
AB  - We present a case of Freeman Sheldon (Whistling Face) syndrome. The anaesthetic
      management of an additional cervical kyphoscoliosis is discussed.

PMID- 9549750
TI  - Anaesthetic implications of Cornelia de Lange syndrome.

PMID- 9549751
TI  - Rectus sheath block in infants: what suitability?

PMID- 9549752
TI  - Down's syndrome and anaesthesia.

PMID- 9549753
TI  - Is there still a place for halothane in paediatric anaesthesia?

PMID- 9549754
TI  - There is no longer a place for halothane in paediatric anaesthesia.

PMID- 9549755
TI  - Signal transduction pathways regulating hematopoietic differentiation.

PMID- 9549756
TI  - Aldose reductase in glucose toxicity: a potential target for the prevention of
      diabetic complications.

PMID- 9549757
TI  - The pharmacology of the ductus arteriosus.

PMID- 9549758
TI  - Therapeutic inhibition of the complement system.
AB  - The use of powerful methodologies in molecular biology, biochemistry, and
      physiology in the last 2 decades had led to impressive progress in our
      understanding of the mechanisms of complement activation and its role as either a
      protective or a pathogenic factor in human disease. With respect to disease
      pathogenesis, the complexity of the complement cascade provides opportunities for
      several different therapeutic targets within the complement pathways. More than a
      century after complement was first described, we are about to witness in the near
      future the availability of a variety of complement inhibitors for specific
      therapies. Progress in the area of xenotransplantation has been substantial, but
      formidable obstacles remain to selective inhibition of the factors that block
      successful clinical xenotransplantation. Bispecific antibodies, designed to
      enhance rather than inhibit existing complement pathways, hold strong promise for
      the clearance of viral and bacterial pathogens from the circulation.

PMID- 9549759
TI  - Perchlorate and the thyroid gland.
AB  - Perchlorate competitively blocks iodide from entering the thyroid by an effect on
      the Na+/I- symporter thus preventing the further synthesis of thyroid hormone but
      has no effect on the iodination process itself. It is concentrated by thyroid
      tissue in a manner similar to iodide but is not significantly metabolized in the
      gland or peripherally. What is not settled is whether there are additional
      perchlorate effects on iodide transport. Perchlorate has a fast turnover in the
      body and requires frequent daily doses for therapy of thyrotoxicosis. Perchlorate
      appears to be substantially more effective against large iodide loads than the
      thionamides, and, with long-term iodide contamination, combined therapy of
      perchlorate (with < or = 1 g/day) and thionamides is recommended for the more
      severe cases of thyrotoxicosis that may result from excess iodide or iodide
      generating organic compounds, as for example with amiodarone. After approximately
      30 days, the perchlorate dosage can be tapered or stopped, continuing with
      thionamides alone. This markedly increases its safe use. Despite serious side
      effects during its early use, lower dosages and shorter treatment periods appear
      to have prevented such reactions in its recent reintroduction, mostly for
      amiodarone-induced thyroid dysfunction. Perchlorate can also protect against
      inhibition of thyroid function and the resulting hypothyroidism caused by excess
      iodide, presumably by reducing the formation of an iodinated inhibitor. The
      reduction of the iodide pool by perchlorate thus has dual effects--reduction of
      excess hormone synthesis and hyperthyroidism, on the one hand, and reduction of
      thyroid inhibitor synthesis and hypothyroidism on the other. Perchlorate remains
      very useful also as a single dose application in tests measuring the discharge of
      radioiodide accumulated in the thyroid as a result of many different disruptions
      in the further metabolism of iodide in the thyroid gland.

PMID- 9549760
TI  - Renal drug metabolism.

PMID- 9549761
TI  - XVI. International Union of Pharmacology recommendations for the nomenclature of
      neuropeptide Y, peptide YY, and pancreatic polypeptide receptors.

PMID- 9549762
TI  - The genetics of sporadic and inherited breast cancer.

PMID- 9549763
TI  - Mammographic evaluation of the augmented breast.

PMID- 9549764
TI  - Survey of alcohol, drug use by radiologic technologists. ASRT Research and
      Development Committee.
AB  - This article describes the results of a survey investigating use of alcohol and
      illicit drugs by radiologic technologists. Overall, survey results suggest that
      few radiologic technologists have a problem with the abuse of alcohol and drugs.
      However, the survey indicates that approximately 3% to 4% of radiologic
      technologists may suffer from some type of substance abuse problem, with alcohol
      abuse more common than drug abuse. These findings correlate with studies that
      reveal similar rates of substance abuse among physicians, nurses and pharmacists.
      Because the abuse of alcohol and drugs affects the quality of patient care, the
      authors recommend that professional organizations identify and assist radiologic
      technologists who suffer from substance abuse and that they promote greater
      awareness of the problem through education. The authors also recommend that an
      awareness of the effects of substance abuse be included in the professional
      curriculum.

PMID- 9549765
TI  - Fast FLAIR techniques in MR imaging of the brain.
AB  - Fast FLAIR (fluid attenuated inversion recovery) is a magnetic resonance imaging
      technique used primarily for neurological imaging of the brain. This technique
      uses an advanced software package that employs basic inversion recovery
      principles to help differentiate between pathology and normal brain parenchyma
      without interference from high-signal cerebral spinal fluid. This article reviews
      the applications of fast FLAIR techniques in MR imaging of the brain.

PMID- 9549766
TI  - Neonatal shielding: a danger or a benefit?

PMID- 9549767
TI  - CE is one path to professionalism.

PMID- 9549768
TI  - Positioning technique needs attention.

PMID- 9549769
TI  - Prolonging life for mesothelioma patients.

PMID- 9549770
TI  - Curly cues.

PMID- 9549771
TI  - Ulna deviation: this way or that way?

PMID- 9549772
TI  - How to make active learning work for you.

PMID- 9549773
TI  - Schizophrenia as a transcallosal misconnection syndrome.
AB  - Schizophrenic symptoms are conceived as arising from inter-individual variability
      in the distribution of those fibres that connect asymmetrical regions of the
      hemispheres related to language. Language (a bihemispheric phenomenon) arose as a
      result of a genetic change that allowed the two hemispheres to develop with a
      degree of independence. One component, the phonological output sequence, became
      localised to the dominant hemisphere, interacting through the corpus callosum
      with other component functions, including the associated meanings, in the non
      dominant hemisphere. Nuclear symptoms are a consequence of failure of segregation
      of these two functions. This failure is associated with abnormal connectivity
      between the hemispheres and relates particularly to those regions that are late
      developing and differ between the sexes.

PMID- 9549774
TI  - The disconnection hypothesis.
AB  - This article reviews the disconnection hypothesis of schizophrenia and presents a
      mechanistic account of how dysfunctional integration among neuronal systems might
      arise. This neurobiological account is based on the central role played by
      neuronal plasticity in shaping the connections and the ensuing dynamics that
      underlie brain function. The particular hypothesis put forward here is that the
      pathophysiology of schizophrenia is expressed at the level of modulation of
      associative changes in synaptic efficacy; specifically the modulation of
      plasticity in those brain systems responsible for emotional learning and memory,
      in the post-natal period. This modulation is mediated by ascending
      neurotransmitter systems that: (i) have been implicated in schizophrenia; and
      (ii) are known to be involved in consolidating synaptic connections during
      learning. The proposed pathophysiology would translate, in functional terms, into
      a disruption of the reinforcement of adaptive behaviour that is consistent with
      the disintegrative aspects of schizophrenic neuropsychology.

PMID- 9549775
TI  - Does dysplasia cause anatomical dysconnectivity in schizophrenia?
AB  - Evidence is reviewed that dysplastic brain development in the second half of
      pregnancy predisposes to schizophrenia. We suggest that an important corollary of
      aberrant development at this stage of ontogenesis is abnormal afferentation of
      the cortical plate, and that this may be macroscopically measurable in terms of
      abnormal correlational structure in adult brain imaging data. This prediction is
      tested by analysis of multiple cortical volume measures on magnetic resonance
      imaging data acquired from 35 male right-handed schizophrenics and 35 matched
      controls. There are no significant differences between groups in global, intra
      hemispheric or inter-hemispheric correlational structure; but schizophrenics are
      shown to have significantly reduced dependencies between frontal and temporal
      lobe volumes, and frontal and hippocampal volumes, in the left hemisphere. We
      conclude that anatomical dysconnectivity (between frontal and temporal cortex) in
      schizophrenia may be caused by dysplasia.

PMID- 9549776
TI  - Reduced corticocortical connectivity can induce speech perception pathology and
      hallucinated 'voices'.
AB  - Reciprocal interactions between multiple cortical areas are required for higher
      order cognitive processes in animals and humans. A growing body of evidence
      suggests that reduced cortical connectivity is associated with schizophrenia. We
      have used neural network computer simulations to characterize symptoms and
      cognitive pathology that could arise from connectivity reductions. When this
      pathology was reproduced in simulations of speech perception networks,
      spontaneous percepts analogous to hallucinated speech were induced due to the
      emergence of 'locked-in' or 'parasitic' states. We propose that these simulations
      provide a model for hallucinated 'voices' reported by actual schizophrenic
      patients. The 'hallucinogenic' model of speech perception also demonstrated
      subtle speech perception impairments. We have demonstrated similar impairments
      when assessing schizophrenic patients reporting 'voices', but not when assessing
      similarly diagnosed patients not reporting this symptom. The model also
      demonstrates how a 'hypodopaminergic' state can reverse cognitive pathology
      arising from connectivity disturbances.

PMID- 9549777
TI  - Schizophrenia as a consequence of brain evolution.
AB  - Connectionist integration of central nervous system function may have proceeded
      by a process of biological trial and error throughout brain evolution. As
      existing structures enlarged, and as new elements of brain function were added,
      misconnectionist variants could arise. This might account for a number of
      developmental syndromes in the human brain including schizophrenia. Ultimately,
      these would derive from aspects of hominid brain evolution and its vertebrate
      ancestry.

PMID- 9549778
TI  - No association of apolipoprotein epsilon 4 allele with schizophrenia even in
      cognitively impaired patients.
AB  - Given the strong association of the apolipoprotein E (apoE) allele epsilon 4
      (epsilon 4) with Alzheimer's disease or cognitive decline in elderly, we tested
      whether cognitive performance in schizophrenic subjects is associated with an
      increase in the frequency of the ApoE epsilon 4 allele. Our data indicate that in
      our sample: (1) there is no association between schizophrenia and the ApoE
      epsilon 4 allele; and (2) the ApoE epsilon 4 allele is not of major importance
      with regard to the cognitive decline observed in schizophrenia.

PMID- 9549779
TI  - Types and characteristics of remote memory impairment in schizophrenia.
AB  - Remote memory, as the term is used in the present study, refers to semantic
      information or autobiographical information for events and facts that are thought
      to be stored in the neocortex. In schizophrenia, findings of abnormalities in
      remote memory have been reported. However, it is unclear whether these are due to
      retrieval factors or other factors (e.g. paucity of information, disorganized
      lexicosemantic representations). Furthermore, it is unclear whether there is a
      temporal gradient in remote memory. In the first study, we utilized a cueing
      procedure for semantic fluency in order to determine whether retrieval factors
      play a marked role in impairments. In comparing patients with schizophrenia to
      patients with affective disorder and normal controls, we found that cueing had an
      equivalent effect upon all groups, suggesting that marked retrieval deficits were
      not the primary determinant of poor performance in fluency. Furthermore, we found
      that semantic fluency was disproportionately impaired vis-a-vis phonologic
      fluency, suggesting that abnormalities may be greater in storage areas presumed
      to be in temporal parietal cortex rather than in prefrontal cortex (which has
      been associated with retrieval deficits). In the second study, we examined the
      temporal gradient of autobiographical memory in patients with schizophrenia and
      normal controls. Whereas normal controls exhibited high and equivalent
      performance across childhood, early adult, and recent memories, patients with
      schizophrenia exhibited a u-shaped profile perhaps unique in the neuropsychiatric
      literature. This may reflect a combination of secondary memory impairments which
      effect the acquisition of new information coupled to very mildly accelerated rate
      of forgetting, 'recency' effects, and/or inefficient encoding. Taken together,
      these studies provide further support for the notion that schizophrenia has a
      relatively unique pattern of neuropsychological deficit based on neocortical
      dysfunction that includes, though is not restricted to, temporoparietal regions.

PMID- 9549780
TI  - Assessing intellectual functioning in persons with schizophrenia spectrum
      disorders using a seven subtest short form of the WAIS-R.
AB  - The purpose of this study was to examine the concurrent validity of a Wechsler
      Adult Intelligence Scale-Revised (WAIS-R) seven subtest short form. Researchers
      have shown that the IQ scores estimated by this short form correlate highly with
      full-form IQ scores in several patient populations. We compared the full WAIS-R
      scores with the seven subtest short form estimated IQs in a sample of patients
      with psychotic disorders (n = 190). The VIQs, PIQs, and FSIQs estimated by the
      short form were highly correlated with the full form IQs (rs ranging from 0.95 to
      0.98). Similar to previous research, the mean difference scores were small
      (ranging from one point to virtually no difference). In general, the seven
      subtest short from has adequate concurrent validity and is suitable for assessing
      intellectual functioning in persons with psychotic disorders.

PMID- 9549781
TI  - Operant conditioning and the orbitofrontal cortex in schizophrenic patients:
      unexpected evidence for intact functioning.
AB  - Neuroimaging and neuropsychological studies have consistently implicated
      dorsolateral prefrontal cortex as abnormal in schizophrenia. However, other areas
      of frontal cortex have received far less attention. In particular, few studies
      have examined orbital frontal regions with other than olfactory tests. In the
      present study we wished to assess the functional capability of orbital frontal
      cortex using a test developed by Bechara et al. (1994) that assesses a subject's
      capacity to acquire a preference through reward and punishment, using a gambling
      task that involved gains and losses of play money. Thirty normal subjects and 12
      patients with schizophrenia (three undifferentiated, eight paranoid, one
      schizoaffective) comprised the sample in the present study. We found that
      patients with schizophrenia exhibited a pattern of findings similar to that of
      normals and dissimilar to that of patients with known orbital frontal damage. In
      our study, both normal subjects and schizophrenic patients chose most frequently
      from decks of cards in which there were frequent rewards and infrequent
      penalties, as might be expected on the basis of operant conditioning literature.
      We also found that performance on this task was not correlated with tests of
      working memory or long-term memory, suggesting that the development of a
      preference may occur implicitly. Our findings also argue against a general
      deficit in schizophrenia, as performance on the gambling task appeared relatively
      uncompromised.

PMID- 9549782
TI  - Brain torque and sex differences in schizophrenia.
AB  - The opposing asymmetry of the frontoparietal brain regions has been referred to
      as 'torque' and may be used as an index of speed of neurodevelopment. It has been
      recently suggested that torque is minimized in male schizophrenia, reflecting
      anomalous neurodevelopment. This study examined volumetric and linear torque in a
      group of 20 schizophrenia patients and 20 healthy individuals; all were right
      handed and under the age of 46 years. None of the main or interaction effects on
      torque were statistically significant, although the sex difference in torque
      among schizophrenia patients (male larger than female) was more than seven times
      that in healthy subjects. Torque was significantly associated with years of
      education and age of illness onset (schizophrenia). These findings support the
      hypothesis that slowed neurodevelopment may be associated with male schizophrenia
      and may contribute to earlier age of onset and fewer years of education.

PMID- 9549783
TI  - Spatial accuracy of primary and secondary memory-guided saccades in schizophrenic
      patients.

PMID- 9549784
TI  - Potential role for the narcolepsy- and multiple sclerosis-associated HLA allele
      DQB1*0602 in schizophrenia subtypes.

PMID- 9549785
TI  - Anatomic considerations of C2 nerve root ganglion.
AB  - STUDY DESIGN: Dissection and observation of the dorsal root ganglion of the
      second cervical spinal nerve bilaterally. OBJECTIVES: To determine the position
      of the C2 dorsal root ganglion and the heights of the C2 ganglion and its
      corresponding foramen. SUMMARY OF BACKGROUND DATA: The dorsal root ganglion has
      been well studied in the middle and lower cervical spine and in the lumbar spine.
      In no previous study are the position and height of the C2 dorsal root ganglion
      and its corresponding foramen described. METHODS: Fifteen cadaveric cervical
      spines were exposed posteriorly. The C2 nerve roots and ganglia were dissected
      between the arch of the atlas and the lamina of the axis. The heights of the C2
      ganglion and foramen were measured. The location of the C2 ganglion was also
      macroscopically observed. RESULTS: The heights of the C2 ganglion and foramen are
      5.7 +/- 0.8 mm and 7.7 +/- 1.2 mm, respectively. The C2 ganglion occupies 76% of
      the foramen height. All C2 dorsal root ganglia are confined within foramens
      between the arch of the atlas and the lamina of the axis. CONCLUSIONS: The C2
      dorsal dorsal root ganglia are all proximally placed and occupy most of the
      foramen height, which may render the C2 ganglion vulnerable to entrapment.

PMID- 9549786
TI  - The role of prophylactic antibiotics in spinal instrumentation. A rabbit model.
AB  - STUDY DESIGN: A rabbit model was used to test the efficacy of cefazolin
      administered in various therapeutic regimens in preventing iatrogenic
      Staphylococcus aureus infections during spinal instrumentation. OBJECTIVE: To
      assess the efficacy of various prophylactic therapeutic regimens of cefazolin in
      preventing iatrogenic S. aureus infections during spinal instrumentation. SUMMARY
      OF BACKGROUND DATA: Previous studies have not dealt specifically with the
      occurrence of iatrogenic S. aureus infections during spinal instrumentation in a
      prospective fashion. METHODS: Twenty New Zealand White rabbits underwent a
      posterior approach to the lumbar spine. Fifteen of the animals then had double
      braided 26-gauge surgical wire placed around bilateral L3-L4 and L4-L5 facet
      joints. A standardized volume of a 103 S. aureus/mL of solution was then
      inoculated onto the fusion-hardware site in all rabbits. The rabbits were divided
      into four groups receiving various antibiotic dose regimens. Five days after
      surgery, the animals were killed, and cultures were obtained. RESULTS: All of the
      rabbits receiving no antibiotic had fusion sites infected with S. aureus. None of
      the animals who received prophylactic cefazolin produced cultures that grew S.
      aureus. A specimen from one fusion site cultured Staphylococcus epidermidis,
      which is not sensitive to cefazolin. Analysis of these data using Fisher's exact
      test resulted in a P value of 0.008 when results in antibiotic groups were
      compared with those in a group receiving no antibiotics and a P value of 0.0003
      when all groups were compared. CONCLUSIONS: This model was valid and reproducible
      for the study of spinal instrumentation and infection. In addition, the data
      support the efficacy and use of prophylactic intravenous antibiotics in
      preventing infection in spinal instrumentation and fusion surgery.

PMID- 9549787
TI  - Keratan sulfate as a potential biomarker of loading of the intervertebral disc.
AB  - STUDY DESIGN: A review of the literature. OBJECTIVE: To investigate the potential
      of serum levels of keratan sulfate as a biomarker of the effects of loading of
      the spine. SUMMARY OF BACKGROUND DATA: Exposure to mechanical loading of the
      spine causes changes in metabolism of intervertebral discs, eventually leading to
      accelerated disc degeneration. This process is characterized by the degradation
      of proteoglycans, which is reflected by an increase in the blood level of
      proteoglycan components. The serum level of keratan sulfate, an epitope present
      on these proteoglycan components, has been suggested as a marker of changes in
      metabolism of cartilaginous tissues. METHODS: A review of the literature on serum
      keratan sulfate levels in relation to degenerative changes in cartilaginous
      tissue. RESULTS: In a number of studies keratan sulfate in serum was reported to
      be related to degeneration of articular cartilage in patients with
      osteoarthritis. In addition, massive and rapid degradation of intervertebral
      discs was determined to result in a large rise in serum keratan sulfate levels.
      Whether degenerative changes of intervertebral discs induced by mechanical stress
      also cause a detectable increase in serum keratan sulfate should be subjected to
      further investigation. CONCLUSION: Quantification of keratan sulfate in serum
      offers a promising measure for the early effects of mechanical loading of the
      spine, but research is needed for validation.

PMID- 9549788
TI  - Reinforcement of thoracolumbar burst fractures with calcium phosphate cement. A
      biomechanical study.
AB  - STUDY DESIGN: A biomechanical study on the stabilization of thoracolumbar burst
      fractures. OBJECTIVE: To demonstrate that the addition of a calcium phosphate
      cement into the fractured vertebral body through a transpedicular approach is a
      feasible technique that improves the stiffness of a transpedicular screw
      construct. SUMMARY OF BACKGROUND DATA: Short segment pedicle screw
      instrumentation is a commonly used method for reduction and stabilization of
      unstable burst fractures. Recent investigators, however, have reported a high
      rate of instrumentation failure and sagittal collapse when there is a loss of
      anterior column support. In this study, the ability of a new hydroxyapatite
      cement to augment anterior column support was investigated in a burst fracture
      model. METHODS: A cadaveric L1 burst fracture model was stabilized using short
      segment pedicle screw instrumentation. Specially instrumented-pedicle screws
      recorded screw-bending moments. The L1 vertebral body was reinforced with the
      hydroxyapatite cement through a transpedicular approach. Mechanical testing of
      the instrumented and instrumented-reinforced constructs were performed in
      flexion, extension, side bending, and torsion. Construct stiffness and screw
      bending moments were recorded. RESULTS: Transpedicular vertebral body
      reconstruction with hydroxyapatite cement reduced pedicle screw-bending moments
      by 59% in flexion and 38% in extension. Mean initial stiffness in the flexion
      extension plane was increased by 40% (P < 0.05). There were no statistically
      significant differences in these parameters with lateral bending or torsional
      movements. CONCLUSIONS: This hydroxyapatite cement compound augments anterior
      column stability in a burst fracture model. This technique may improve outcomes
      in burst fracture patients without the need for a secondary anterior approach.

PMID- 9549789
TI  - The effects of spinal fixation and destabilization on the biomechanical and
      histologic properties of spinal ligaments. An in vivo study.
AB  - STUDY DESIGN: An animal study was conducted to assess whether different surgical
      procedures of spinal fixation and destabilization would influence the
      biomechanics and histology of lumbar spinal ligaments. OBJECTIVES: To investigate
      the effects of spinal fixation and destabilization as well as surgical
      intervention itself on the biomechanical and histologic properties of lumbar
      spinal ligaments. SUMMARY OF BACKGROUND DATA: Although several investigators have
      reported normal biomechanical properties of different spinal ligaments, there
      have been no studies in which changes in spinal ligament properties, secondary to
      the altered biomechanical environment provided by such surgical procedures as
      spinal fixation and destabilization, have been investigated. METHODS: Thirty-six
      mature sheep were divided into four groups: Group I: nonsurgical control: Group
      II: sham operation consisting of bilateral posterolateral exposure at L4-L5;
      Group III: spinal fixation using transpedicular screws and plates and bilateral
      posterolateral bone graft at L4-L5; and Group IV: spinal destabilization
      consisting of bilateral facetectomy and anterior discectomy at L4-L5. Four months
      after surgery, the biomechanical analysis included destructive tensile testing of
      four different bone-ligament-bone complexes at the operative and proximal
      adjacent levels: anterior longitudinal ligament, posterior longitudinal ligament,
      ligamentum flavum, and supraspinous and interspinous ligaments combined.
      Histomorphometric analyses of the vertebral body and spinal ligaments were
      performed histomorphometrically. RESULTS: Biomechanical analysis results
      demonstrated remarkable changes in the structural and mechanical ligament
      properties at the operative level. The fixation group's ligaments showed
      consistent decreases in the ultimate load and elastic modulus compared with those
      parameters in the control group (P < 0.05). Histologically, the fixation group's
      ligamentum flavum showed marked vacuolation in the ligament substance, whereas
      the interspinous ligament exhibited significant insertion changes compared with
      little change in substance. In all eight sheep in Group IV, unintentional
      bilateral facet fusions were obtained; and in all eight animals in Group III with
      pedicle instrumentation and posterolateral fusion, solid arthrodesis was
      exhibited. This allowed a distinction to be made between the stress-shielding
      effect of spinal instrumentation and arthrodesis (Group III) versus spinal fusion
      alone (Group IV) on both spinal ligament and vertebral body. Group II (sham) had
      a significant decrease in supraspinous and interspinous ligaments, but
      nonsignificant decreases in the stress-shielding effect of 10-12% in other
      ligaments. CONCLUSIONS: Posterior spinal instrumentation and fusion led to
      decreased biomechanical properties of the ligamentum flavum, posterior
      longitudinal ligament, and interspinous and supraspinous ligaments. The stress
      shielding effects were ligament dependent and were most pronounced on the
      posterior side. The altered biomechanical environment produced by spinal
      fixation, surgical intervention itself, or nonphysiologic mobilization can affect
      the ligamentous properties in vivo, possibly serving as the impetus for low back
      pain.

PMID- 9549790
TI  - Prediction of load sharing among spinal components of a C5-C6 motion segment
      using the finite element approach.
AB  - STUDY DESIGN: A finite element model of the ligamentous cervical spinal segment
      was used to compute loads in various structures in response to clinically
      relevant loading modes. OBJECTIVE: To predict biomechanical parameters, including
      intradisc pressure, tension in ligaments, and forces across facets that are not
      practical to quantify with an experimental approach. SUMMARY OF BACKGROUND DATA:
      Finite element models of the cervical spine in their present form, because of
      inherent assumptions and simplifications, are not entirely satisfactory for
      studying the biomechanics of the intact, injured, and stabilized cervical spinal
      segment. METHODS: A three-dimensional finite element model of a C5-C6 motion
      segment was developed from serial computed tomographic scans of a ligamentous
      cervical spinal segment. This model included nonlinear ligament definition, fully
      composite intervertebral disc, fluid nucleus, and Luschka's joints. The model
      based displacement predictions were in agreement with the experimental data. This
      model was used to predict load sharing and other related parameters in spinal
      elements in response to various loading modalities. RESULTS: In axial
      compression, 88% of the applied load passed through the disc. The interspinal
      ligament experienced the most strain (29.5%) in flexion, and the capsular
      ligaments were strained the most (15.5%) in axial rotation. The maximum intradisc
      pressure was 0.24 MPa in the flexion with axial compression mode (1.8 Nm + 73.6
      N). The anterior and posterior disc bulges increased with the increase in axial
      compression (up to 800 N). CONCLUSIONS: The results provide new insight into the
      role of various elements in transmitting loads. The model represents significant
      and essential advancement in comparison with previous finite element models,
      making it possible for such models to be used in investigating a broad spectrum
      of clinically relevant issues.

PMID- 9549791
TI  - Metallic artifacts in magnetic resonance imaging of patients with spinal fusion.
      A comparison of implant materials and imaging sequences.
AB  - STUDY DESIGN: Devices for spinal fusion were compared with respect to their
      influence on magnetic resonance images. In addition, different magnetic resonance
      pulse sequences were evaluated to elicit their susceptibility to imaging
      artifacts. OBJECTIVES: To determine the implants with the least imaging artifacts
      as a recommendation for the spine surgeon and to assess the best imaging strategy
      for the radiologist. SUMMARY OF BACKGROUND DATA: For patients who have had
      surgical spinal fusion with instrumentation, magnetic resonance imaging is the
      most favorable diagnostic method. Unfortunately, metallic implants lead to severe
      degradation of image quality. These artifacts depend on the material of the
      implant and on the choice of the pulse sequence. METHODS: The fusion devices were
      mounted on a simple plastic phantom in various combinations and were imaged on
      1.5-T magnetic resonance units. Frequently used types of plates and screws made
      of titanium or steel in various alloys were examined on the phantom with
      routinely used pulse sequences. The results of these examinations were compared
      with those in patient studies involving the same implants as well as the same
      pulse sequences. RESULTS: The least imaging artifacts were caused by titanium
      implants, especially when using shorter screws, wider screw placement, and
      thinner titanium plates. Nevertheless, there were distinct image distortions that
      could lead to erroneous image interpretation. The best images were acquired by
      spin echo (T1), turbo spin echo (T1, T2), and half Fourier single shot turbo spin
      echo (HASTE) sequences. Sequences containing any gradient echo components
      (gradient echo or turbo gradient and spin echo sequence or frequency-selective
      fat saturation techniques) resulted in the highest amount of image degradation.
      CONCLUSION: By choosing appropriate spinal fusion devices as well as pulse
      sequences, postoperative magnetic resonance imaging examinations can give
      acceptable results, in spite of the presence of metallic implants.

PMID- 9549792
TI  - Reciprocal angulation of vertebral bodies in the sagittal plane in an
      asymptomatic Greek population.
AB  - STUDY DESIGN: A prospective study conducted on several roentgenographic
      parameters of the standing sagittal profile of the spine in an asymptomatic Greek
      population. OBJECTIVES: To perform segmental analysis of the sagittal plane
      alignment of the normal thoracic, lumbar, and lumbosacral spines and to compare
      the findings with those derived from similar populations. SUMMARY OF BACKGROUND
      DATA: Until recently, little attention has been paid to the sagittal segmental
      alignment of the spine, and there are only a few studies (in French and American
      populations) in which radiographic analysis of sagittal spinal alignment is
      investigated. METHODS: Ninety-nine consecutive asymptomatic Greek volunteers (38
      men, 61 women), an average age of 52.7 +/- 15 years old (range, 20-79 years),
      were included in this prospective study, on the basis of several inclusion
      criteria. These volunteers were divided into six distinct age groups. The
      radiologic parameters, which were measured (by Cobb's method) on the lateral
      standing roentgenograms of the whole spine were: thoracic kyphosis (T4-T12),
      lumbar lordosis (L1-L5), total lumbar lordosis (T12-S1), distal lumbar lordosis
      (L4-S1), sacral inclination (measured from the line drawn parallel along the back
      of the proximal sacrum and the vertical line), pelvic tilting, vertebral body
      inclination, and relative segmental inclination between pairs of adjacent
      vertebrae. RESULTS: Thoracic kyphosis and lumbar lordosis (T12-S1, L1-L5) were
      not gender related. Thoracic kyphosis increased with age (P < 0.001), the lumbar
      spine (L1-L5) gradually became less lordotic as the thoracic kyphosis increased
      (P < 0.003), and total lumbar lordosis was not age related. Sacral inclination
      correlated strongly with both thoracic kyphosis (P < 0.002) and L1-L5 lordosis (P
      < 0.001). Pelvic tilting correlated strongly with L1-L5 lordosis (P < 0.0075),
      but did not correlate with thoracic kyphosis and age. Vertebral body inclination
      showed a narrow variability in T6-T12 and in L4 and a wide variability in T4, T5,
      L1-L3, and S1. Distal lumbar lordosis represents the 68.6% of the total lumbar
      lordosis. CONCLUSIONS: In the results of this study, a reliable table of
      reference for roentgenographic parameters in the sagittal plane of the spine was
      established in an asymptomatic Greek population. The parameters are similar to
      those used in previous studies. Thus, these data should be considered in
      preoperative planning and postoperative evaluation of achieved correction during
      restoration procedures of the spine in the sagittal plane.

PMID- 9549793
TI  - An assessment of complex spinal loads during dynamic lifting tasks.
AB  - STUDY DESIGN: An electromyogram-assisted free-dynamic lifting model was used to
      quantify the patterns of complex spinal loads in subjects performing various
      lifting tasks. OBJECTIVES: To assess in vivo the three-dimensional complex spinal
      loading patterns associated with high and low risk lifting conditions that
      matched those observed in industrial settings. SUMMARY OF BACKGROUND DATA:
      Combined loading on the spine has been implicated as a major risk factor in
      occupational low back disorders. However, there is a void in the literature
      regarding the role of these simultaneously occurring complex spinal loads during
      manual lifting. METHODS: Eleven male subjects performed symmetric and asymmetric
      lifting tasks with varying speed and weight. Reactive forces and moments at L5-S1
      were determined through the use of electrogoniometers and a force plate. An
      electromyogram-assisted model provided the continuous patterns of three
      dimensional spinal loads under these complex lifting tasks. RESULTS: The results
      showed that complex dynamic motions similar to those observed in risky industrial
      tasks generated substantial levels of combined compressive and shear loads. In
      addition, higher loading rates were observed under these conditions. Unlike
      loading magnitudes, loading rate was a better indicator of dynamic loading
      because it incorporated both the duration and magnitude of net muscle forces
      contributing to total spinal loading during the lifting conditions. CONCLUSIONS:
      Quantification of spinal combined motions and loading in vivo has not been
      undertaken. This study provided a unified assessment of the effects of combined
      or coupled motions and moments in the internal loading of the spine. Dynamic
      lifting conditions similar to those observed in risky industrial situations
      generated unique complex patterns of spinal loading, which have been implicated
      to pose a higher risk to the spinal structure. The higher predicted loading and
      loading rate during asymmetric lifting conditions can be avoided by appropriate
      ergonomic workplace modifications.

PMID- 9549794
TI  - Functional restoration for chronic low back pain. Two-year follow-up of two
      randomized clinical trials.
AB  - STUDY DESIGN: Two randomized, prospective clinical trials involving 238 chronic
      low back disability patients were carried out. Results at 2-year follow-up are
      presented. OBJECTIVES: To compare the clinical outcomes of a multidisciplinary
      functional restoration program with a nontreated control group (Project A) and
      with two less intensive but different training programs (Project B). SUMMARY OF
      BACKGROUND DATA: The effectiveness of functional restoration programs has not
      been firmly established. Results from trials carried out in the United States
      differ from those in trials conducted in other countries. Only a few of these
      studies have been carried out as prospective and randomized clinical studies.
      METHODS: Two hundred thirty-eight patients with chronic low back disability of at
      least 6 months' duration were included. There were 106 patients in project A and
      132 patients in project B. Two years after completion of treatment patients were
      mailed a questionnaire that included questions regarding their work status, pain
      and disability levels, number of sick leave days, number of medical care
      contacts, medication use, physical activity levels, and subjective overall
      assessment of their "back life situation." RESULTS: Patients in both studies were
      comparable at inclusion, except that patients in Project A were recruited from
      all of Denmark, whereas those in Project B were from the greater Copenhagen area.
      Thirteen patients did not report for treatment after randomization. Of the
      remaining 225 patients, 20 (9%) did not complete treatment. The questionnaire
      response rate was 94%. In Project A, those patients receiving treatment
      (functional restoration) reported significantly less contact with the health care
      system, fewer sick leave days, and a less disabled life style during the follow
      up period, compared with reports of patients in the control group. Other effect
      parameters did not demonstrate a significant difference between the two groups.
      In Project B, all effect parameters reported, except leg pain and medication
      usage, were significantly in favor of functional restoration, compared with
      reports from the less intensively treated groups. CONCLUSIONS: The functional
      restoration program seems effective in various parameters compared with the less
      intensive programs, but the differences in outcome in the two parallel studies
      indicate the necessity of testing a treatment program in different settings, in
      that the statistical variation may be a major factor in results of different
      studies.

PMID- 9549795
TI  - Factors influencing wound healing after surgery for metastatic disease of the
      spine.
AB  - STUDY DESIGN: The study group consisted of 53 patients who underwent 75
      operations for spine metastases. Patient and tumor demographic factors,
      preoperative nutritional status, and perioperative adjunctive therapy were
      retrospectively reviewed. OBJECTIVE: To determine the risk factors for wound
      breakdown and infection in patients undergoing surgery for spinal metastases.
      SUMMARY OF BACKGROUND DATA: Spinal fusion using spine implants may be associated
      with an infection rate of 5% or more. Surgery for spine metastases is associated
      with an infection rate of more than 10%. Factors other than the type of surgery
      performed may account for the greater infection rate. METHODS: Data were obtained
      by reviewing patient records. Age, sex, and neurologic status of the patient;
      tumor type and site; and surgical details were noted. Adjunctive treatment with
      corticosteroids and radiotherapy was recorded. Nutritional status was evaluated
      by determining serum protein and serum albumin concentrations and by total
      lymphocyte count. RESULTS: Wound breakdown and infection occurred in 15 of 75
      wounds. No patient or tumor demographic factors other than intraoperative blood
      loss (P < 0.1) were statistically associated with infection. The correlation
      between preoperative protein deficiency (P < 0.01) or perioperative
      corticosteroid administration (P < 0.10) and wound infection was significant.
      There was no statistical correlation between lymphocyte count or perioperative
      radiotherapy and wound infection. CONCLUSIONS: The results indicate that
      preoperative protein depletion and perioperative administration of
      corticosteroids are risk factors for wound infection in patients undergoing
      surgery for spine metastases. Perioperative correction of nutritional depletion
      and cessation of steroid therapy may reduce wound complications.

PMID- 9549796
TI  - An unusual cause of lumbar discitis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To identify an unusual cause of lumbar
      discitis. SUMMARY OF BACKGROUND DATA: Discitis resulting from a foreign body has
      not been reported in the English-language literature. METHOD: A case report is
      reviewed identifying the presence of this foreign object (titanium), erroneously
      implanted into the disc space at L5-S1. Imaging studies identify the location and
      surrounding reaction. RESULTS: The surgical exploration of this disc revealed an
      inflammatory response surrounding the disc with degeneration within the disc
      space. CONCLUSION: If this gynecologic procedure is performed using bone anchors,
      care must be take to ensure that the sacrum is identified before insertion.

PMID- 9549797
TI  - Asymptomatic grotesque deformities of the cervical spine. An occupational hazard
      in railway porters.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To illustrate an extremely rare
      occurrence of chronic, occupational, low-grade trauma leading to asymptomatic
      grotesque cervical spine deformities in railroad station porters. SUMMARY OF
      BACKGROUND DATA: Occupational trauma causing spinal deformities has been
      described in relation to thoracic and lumbar spines in miners. To the authors'
      knowledge, this is the first reported case of asymptomatic cervical spinal
      deformity in railway porters as a result of chronic occupational trauma. METHODS:
      A magnetic resonance imaging study was performed on both patients. RESULTS: The
      magnetic resonance images showed advanced degenerative changes in the cervical
      spine causing obvious deformities, along with apparently normal cord signal
      intensity. CONCLUSIONS: Chronic, occupational, low-grade trauma of the cervical
      vertebral region is extremely unusual in industrialized countries. Nevertheless,
      in view of the increasing mobility of people in general and of the labor force in
      particular, this complication of an occupational exposure deserves attention as
      an unusual cause of cervical spinal deformity.

PMID- 9549799
TI  - Efficacy of five cervical orthoses in restricting cervical motion: a comparison
      study.

PMID- 9549798
TI  - Symptomatic monostotic fibrous dysplasia of the thoracic spine.
AB  - STUDY DESIGN: A case report of monostotic fibrous dysplasia of the thoracic spine
      with symptoms of chest and back pain. OBJECTIVE: To treat this lesion with
      surgery. SUMMARY OF BACKGROUND DATA: Monostotic fibrous dysplasia of the thoracic
      spine is rarely seen. Few reports of this disorder appear in the literature. This
      is the fifth case of monostotic fibrous dysplasia of the thoracic spine presented
      to date. METHODS: The patient was a 48-year-old woman with monostotic fibrous
      dysplasia involving the thoracic spine of the 10th vertebral body and the 10th
      left rib. Surgical removal of the tumor was carried out. The defect was packed
      with hydroxyapatite graft material. Arthrodesis or internal fixation was not
      made. RESULTS: The diagnosis of fibrous dysplasia was made histologically. No
      obvious recurrence of the lesion has been seen for 3 years. CONCLUSION: Surgical
      removal of the tumor and transplantation of hydroxyapatite was effective
      treatment for the reported patient.

PMID- 9549800
TI  - Thermal transport during radiofrequency current therapy of the intervertebral
      disc.

PMID- 9549801
TI  - Missing quality of life data in cancer clinical trials: serious problems and
      challenges.
AB  - Measurement of quality of life (QOL) in cancer clinical trials has increased in
      recent years as more groups realize the importance of such endpoints. A key
      problem has been missing data. Some QOL data may unavoidably be missing, as for
      example when patients are too ill to complete forms. Other important sources are
      potentially avoidable and can broadly be divided into three categories: (i)
      methodological factors; (ii) logistic and administrative factors; (iii) patient
      related factors. Logistic and administrative factors, for example, staff
      oversights, have proven to be most important. Since most QOL measurements require
      patient self-report, it is usually not possible to rectify the failure to collect
      baseline data or any follow-up assessments. There is strong evidence that such
      data are not 'missing at random', and cannot be ignored without introducing bias.
      Although several approaches to the analysis of partly missing data have been
      described, none is entirely satisfactory. Prevention of avoidable missing data is
      better than attempted cure. In July 1996, an international conference on missing
      QOL data in cancer clinical trials reported the experience of most major groups
      involved. This paper will serve as an introduction to the problem and provide an
      estimation of its magnitude, and approaches to its prevention and solution.

PMID- 9549802
TI  - Quality of life studies of the Australian New Zealand Breast Cancer Trials Group:
      approaches to missing data.
AB  - The purpose of this paper is to describe the degree of compliance with quality of
      life measures in two clinical trials conducted by the Australian New Zealand
      Breast Cancer Trials Group comparing different chemotherapy policies for
      metastatic breast cancer. Quality of life was assessed by the patient using
      linear analogue scales and by the physician using the Spitzer QLI. Compliance was
      generally good, ranging from 66 per cent to 79 per cent in the earlier study, and
      from 63 per cent to 97 per cent in the later study. Compliance with physician
      rated quality of life was consistently slightly better than for patient self
      assessment. The results of physician and patient assessments were generally
      consistent, but there was a systematic bias toward lower quality of life (as
      assessed by the physician) in patients who failed to comply with self-assessment.
      Our conclusions were that quality of life can be assessed in large scale multi
      institution clinical trials in metastatic breast cancer. The results are
      important in assessing treatment comparisons. Missing data cannot be assumed to
      be similar to those available. Optimal assessment of quality of life therefore
      requires careful prospective attention to complete data collection.

PMID- 9549803
TI  - Compliance issues in quality of life assessment: experiences of two Cancer
      Research Campaign sponsored groups.

PMID- 9549804
TI  - Missing data in quality of life research in Eastern Cooperative Oncology Group
      (ECOG) clinical trials: problems and solutions.
AB  - Incorporation of quality of life (QOL) investigation into Eastern Cooperative
      Oncology Group (ECOG) multi-centre clinical trials has led to innovative
      strategies for protocol design and high quality data collection. A scientific
      advisory committee reviews protocol design components, measurement selection,
      timing of assessments and compliance issues. Extensive educational programmes
      provide information about the scientific and clinical relevance of QOL protocols,
      as well as practical strategies for data collection and management. Compliance
      with QOL data collection standards is prospectively monitored and evaluated.
      Preliminary results from eight ECOG-run protocols found overall compliance to be
      approximately 85 per cent (94 per cent at baseline and 73 per cent during
      treatment). Selected patient and institutional factors were evaluated for their
      association with compliance.

PMID- 9549805
TI  - Quality of life as an endpoint in EORTC clinical trials. European Organization
      for Research and Treatment for Cancer.
AB  - For more than 30 years the European Organization for Research and Treatment for
      Cancer (EORTC) has conducted, co-ordinated, and stimulated research on the
      experimental and clinical bases of treatment of cancer and related problems. For
      more than a decade the EORTC has included quality of life as an outcome measure
      in some of its trials. The number of clinical studies that include QOL as an
      evaluation endpoint has increased rapidly in the last few years, and is still
      increasing steadily. This necessitated a careful and critical evaluation of
      procedures and results so far in order to generate appropriate guidelines and
      procedures for incorporating QOL issues in all stages of the clinical trial
      process, including protocol writing, data collection, data analysis, and
      reporting of results. This paper provides an overview of the types and the design
      of studies, data management of quality of life assessment, compliance, missing
      data and lessons learned during the past years with respect to QOL assessments in
      the EORTC studies.

PMID- 9549806
TI  - Compliance with QOL assessment in multi-centre German breast cancer trials.
AB  - The compliance with QOL assessment in German breast cancer trials is reported.
      The results indicate that the response to fill in QOL forms in cancer clinical
      trials seems to depend more on the clinical centre and the attitude of the
      treating physician than the individual patient. A strategy of globally
      eliminating centres that produce high rates of missing QOL data from the analysis
      of QOL is discussed. The adoption of such a strategy will reduce the number of
      patients available for analysis, but on the other hand increase the relative
      amount of non-missing data.

PMID- 9549807
TI  - The multi-centre assessment of quality of life: the Interdisciplinary Group for
      Cancer Care Evaluation (GIVIO) experience in Italy.
AB  - One of the main issues to be considered in conducting clinical trials concerns
      the presence of missing data. This aspect is particularly relevant in oncology
      longitudinal studies, characterized by a long follow-up, and especially in
      quality of life studies where there is still little knowledge about patients'
      characteristics that predict loss of data. Since the middle of the 1980s the
      GIVIO (Interdisciplinary Group for Cancer Care Evaluation) co-operative group has
      been involved in conducting quality of life assessment studies, also focusing on
      the development of some strategies aimed at the minimization of missing data. In
      this paper we report on the results of two trials, which are now completed,
      concerning the quality of life assessment in a sample of breast and colon cancer
      patients. In order to cope with the problem of missing data, in both the trials
      the strategy of follow-up mailing was adopted, which proved to be an effective
      way to increase the response rate by nearly 50 per cent at each time point.

PMID- 9549808
TI  - Quality of life assessment in International Breast Cancer Study Group (IBCSG)
      trials: practical issues and factors associated with missing data.
AB  - We report on our experience of quality of life (QL) assessment in adjuvant
      clinical trials of the International Breast Cancer Study Group (IBCSG), with
      special emphasis on cultural and logistical aspects of international organization
      that are unique to this group. Data are presented regarding submission rates of
      assessments before and after treatment failure, and timing of assessments
      relative to chemotherapy administration. To identify areas where rates might be
      improved, we investigated the association between missing data and
      sociodemographic and biomedical factors, treatment assignment, institution,
      chemotherapy compliance and toxicity in a trial of adjuvant chemoendocrine
      therapy for post-menopausal patients with breast cancer (IBCSG VII). The factors
      most highly associated with missing data were institution and chemotherapy
      compliance.

PMID- 9549809
TI  - Completion rates in health-related quality-of-life assessment: approach of the
      National Cancer Institute of Canada Clinical Trials Group.
AB  - The approach of the National Cancer Institute of Canada Clinical Trials Group to
      measuring compliance, that is, completion rates, for health-related quality of
      life questionnaires is presented. Completion rates can be measured at the
      institutional, patient, questionnaire and item levels for baseline, on-treatment
      and off-treatment follow-up study periods. Time windows are defined for each
      expected completion time. In seven completed clinical trials, completion rates
      were high with more than 93 per cent of patients completing questionnaires in the
      specified time windows at baseline and while on-treatment. The rate while on off
      treatment follow-up is still acceptable at 85 per cent. The proportions of
      analysable questionnaires were 97.6 per cent, 82.0 per cent and 77.0 per cent
      respectively, at the three study periods. Item completion rates within
      questionnaires were high at 95.5 per cent or more. The variables most likely to
      influence baseline and on-treatment questionnaire completion rates were breast
      cancer, ovarian cancer, metastases and study centre size.

PMID- 9549810
TI  - Compliance with quality of life data collection in the National Surgical Adjuvant
      Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial.
AB  - This paper describes compliance with the completion of a quality of life
      questionnaire in the Breast Cancer Prevention Trial, a large multi-centre
      randomized trial that is studying the efficacy of Tamoxifen in preventing breast
      cancer. In the first 4875 women enrolled in the control arm of the study, there
      was a very high rate of questionnaire completion at baseline, 3 months, 6 months
      and 12 months of follow-up (89.8 per cent completed forms at 12 months). The
      sample was examined according to demographic and risk factors, as well as by
      recruitment cohort. There was a significantly poorer compliance rate for the most
      recently recruited cohort that was followed-up during a time of substantial
      external negative publicity related to clinical trial research. Nevertheless, the
      overall compliance with completion of quality of life data in this trial is very
      high, which is probably attributable to the high educational status of the trial
      participants.

PMID- 9549811
TI  - Compliance in quality of life data: a Norwegian experience.
AB  - Compliance is of extreme importance in assessing quality of life since lost data
      never can be retrieved. In order to assess this issue in various studies, a cross
      sectional study in cured cancer patients, three prospective trials and a
      normative study were explored. In the cross-sectional study 82 per cent of the
      patients completed the questionnaires after one reminder. More females than males
      answered the questionnaires. The compliance rate varied from 99 per cent to 62
      per cent in the prospective studies depending upon time after inclusion. It seems
      that compliance decreases during follow up, primarily because of disease
      progression. In one of the prospective studies low compliance rate (approximately
      30 per cent) was found in the questionnaire assessing religious issues. In the
      normative study 68 per cent of the population completed the questionnaire. No
      gender differences were found, but younger males and elderly women were poor
      compliers. In conclusion, our data support that most patients complete quality of
      life questionnaires. It seems that patients with inferior education, reduced
      physical function and with progressive/terminal disease are low compliers.
      Introduction of the first quality of life questionnaires to the patients is of
      great importance. Detailed information about the study should be given and the
      importance of completing the questionnaires should be underlined.

PMID- 9549812
TI  - Practical issues in quality of life assessment in multicentre trials conducted by
      the Swiss Group for Clinical Cancer Research.
AB  - Quality of life (QOL) assessment has become an integrated part in some advanced
      disease trials and to a lesser extent in early disease trials conducted by the
      Swiss Group for Clinical Research (SAKK). In general, the concept of QOL
      endpoints and the additional work of collecting these data is well accepted by
      patients, nurses and physicians. The QOL form submission rates in recently
      completed trials in advanced disease have improved in response to ongoing staff
      training and supervision as well as direct and personal interventions in the
      local centres, with 82-86 per cent before treatment failure, and 59-88 per cent
      at failure. The main source of missing data are local administrative problems, in
      particular staff oversights.

PMID- 9549813
TI  - Ensuring the quality of quality of life data: the Southwest Oncology Group
      experience.
AB  - The Southwest Oncology Group (SWOG) has successfully included quality of life
      (QOL) questionnaires in selected oncology treatment trials. Extensive quality
      control procedures have been necessary for obtaining and maintaining good
      questionnaire submission rates. Since the first QOL study was activated in SWOG
      in 1990, the Group has found it increasingly necessary to incorporate centralized
      monitoring of the QOL assessment schedule. Successful quality control strategies
      are presented. Current submission rates for five SWOG phase III treatment trials
      (both open and closed) and one chemoprevention trial are presented for those
      scheduled QOL assessments for which we have follow-up data. Reasons for missing
      QOL questionnaires and the extent of missing data within submitted QOL
      questionnaires are described for two different disease contexts: a trial for
      patients with advanced stage disease, and a trial for patients with earlier stage
      disease.

PMID- 9549814
TI  - Statistical analysis of quality of life with missing data in cancer clinical
      trials.
AB  - We summarize issues that arise when considering quality of life (QOL) data in
      cancer clinical trials, especially those related to missing data. We describe
      different types of missing data mechanisms, and discuss ways of assessing and
      testing missing data mechanisms. A section on presentation of study design and
      results describes how graphical displays can effectively document the extent of
      the missing data problem, as well as describe its impact on interpretation of
      results. Finally, we describe several different statistical methods used to
      analyse repeated measures, with an emphasis on their properties and their ability
      to adequately handle different types of missing data mechanisms. We make
      recommendations as to the most appropriate methods, and suggest important
      directions for future research.

PMID- 9549816
TI  - Incomplete quality of life data in randomized trials: missing items.
AB  - Missing data has been a problem in many quality of life studies. This paper
      focuses upon the issues involved in handling forms which contain one or more
      missing items, and reviews the alternative procedures. One of the most widely
      practised approaches is imputation using the mean of all observed items in the
      same subscale. This, together with the related estimation of the subscale score,
      is based upon traditional psychometric approaches to scale design and analysis.
      We show that it may be an inappropriate method for many of the items in quality
      of life questionnaires, and would result in biased or misleading estimates. We
      provide examples of items and subscales which violate the psychometric
      foundations that underpin simple mean imputation. A checklist is proposed for
      examining the adequacy of simple imputation, and some alternative procedures are
      indicated.

PMID- 9549815
TI  - Why are missing quality of life data a problem in clinical trials of cancer
      therapy?
AB  - Assessment of health related quality of life has become an important endpoint in
      many cancer clinical trials. Because the participants of these trials often
      experience disease and treatment related morbidity and mortality, non-random
      missing assessments are inevitable. Examples are presented from several such
      trials that illustrate the impact of missing data on the analysis of QOL in these
      trials. The sensitivity of different analyses depends on the proportion of
      assessments that are missing and the strength of the association of the
      underlying reasons for missing data with disease and treatment related morbidity
      and mortality. In the setting of clinical trials of cancer therapy, the
      assumption that the data are missing completely at random (MCAR) and analyses of
      complete cases is usually unjustified. Further, the assumption of missing at
      random (MAR) may also be violated in many trials and models appropriate for non
      ignorable missing data should be explored. Recommendations are presented to
      minimize missing data, to obtain useful documentation concerning the reasons for
      missing data and to perform sensitivity analyses.

PMID- 9549817
TI  - Incomplete quality of life data in randomized trials: missing forms.
AB  - Analysing quality of life (QOL) data may be complicated for several reasons, such
      as: repeated measures are obtained; data may be collected on ordered categorical
      responses; the instrument may have multidimensional scales, and complete data may
      not be available for all patients. In addition, it may be necessary to integrate
      QOL with length of life. The major undesirable effects of missing data, in QOL
      research, are the introduction of biases due to inadequate modes of analysis and
      the loss of efficiency due to reduced sample sizes. Currently, there is no
      standard method for handling missing data in QOL studies. In fact, there are very
      few references to methods of handling missing data in this context. The aim of
      this paper is to provide an overview of methods for analysing incomplete
      longitudinal QOL data which have either been presented in the QOL literature or
      in the missing data literature. These methods of analysis include complete case,
      available case, summary measures, imputation and likelihood-based approaches. We
      also discuss the issue of bias and the need for sensitivity analyses.

PMID- 9549818
TI  - Suggestions for the presentation of quality of life data from clinical trials.
AB  - Quality of life (QOL) data is complex since it is both multidimensional and
      longitudinal. This complexity is compounded with its unbalanced nature through
      missing observations as a consequence of patient non-compliance with assessment
      schedules, and, for example, in cancer clinical trials data absence due to
      patient attrition often through death. QOL data poses difficulties for
      presentation and analysis and hence interpretation. This paper illustrates, using
      data from a randomized trial of the United Kingdom Medical Research Council Lung
      Cancer Working Party, a step-by-step approach to presentation of QOL data. This
      begins with a description of compliance and its relationship with patient
      attrition caused by death, to a final summary profile to indicate change over
      time. We recognize that no single summary statistic is likely to be able to
      encapsulate all the subtleties of QOL data. We stress the importance of examining
      data graphically before performing detailed analysis and also to facilitate
      interpretation in the final clinical report. Although a description of analytical
      methods is not the purpose of this paper, we draw attention to the need for
      imputing missing values and to the (multi-level) modelling approach to
      summarizing the data, both essential adjuncts to the less formal methods
      described here.

PMID- 9549819
TI  - Practical approaches to minimize problems with missing quality of life data.
AB  - Missing information on quality of life (QOL) is a significant problem in many
      cancer trials particularly for patients with advanced disease, where clinical
      deterioration may be a reason for not responding to quality of life assessments.
      Examples from four clinical trials are presented where non-respondents to quality
      of life assessments have poorer health than respondents. In this context,
      auxiliary outcome variables, such as health status, may be useful proxies in
      assessing the impact of missing QOL data on estimated treatment effects. This
      approach is illustrated in a trial of palliative treatment in advanced cancer. A
      method for imputation of missing QOL data based on auxiliary outcome variables is
      also illustrated. However, the most effective method of minimizing the problem of
      missing data is in designing the trial with preventative strategies in place.
      Since some missing data due to deteriorating health may still occur, the design
      should include the collection of auxiliary QOL information. Preventative
      strategies are illustrated with an ongoing trial in advanced breast cancer.

PMID- 9549820
TI  - Identifying the types of missingness in quality of life data from clinical
      trials.
AB  - This paper discusses methods of identifying the types of missingness in quality
      of life (QOL) data in cancer clinical trials. The first approach involves
      collecting information on why the QOL questionnaires were not completed. Based on
      the reasons provided one may be able to distinguish the mechanisms causing
      missing data. The second approach is to model the missing data mechanism and
      perform hypothesis testing to determine the missing data processes. Two methods
      of testing if missing data are missing completely at random (MCAR) are presented
      and applied to incomplete longitudinal QOL data obtained from international multi
      centre cancer clinical trials. The first method (Ridout, 1991) is based on a
      logistic regression and the second method (Park and Davis, 1993) is based on an
      adaptation of weighted least squares. In one application (advanced breast cancer)
      missing data was not likely to be MCAR. In the second application (adjuvant
      breast cancer) the missing mechanism was dependent on the QOL scale under study.
      MCAR and missing at random (MAR) have distinct consequences for data analysis.
      Therefore it is relevant to distinguish between them. However, if either MCAR or
      MAR hold, likelihood or Bayesian inferences can be based solely on the observed
      data, although for MAR, depending on the research question, modelling the dropout
      mechanism may still be necessary. Distinguishing between MAR and missing not at
      random (MNAR) is not trivial and relies on fundamentally untestable assumptions.

PMID- 9549822
TI  - A comparative analysis of quality of life data from a Southwest Oncology Group
      randomized trial of advanced colorectal cancer.
AB  - Longitudinal quality of life measurements from an advanced-stage cancer clinical
      trial are analysed using a variety of methods, and the results compared. The
      methods used require different assumptions about the mechanism that produces the
      missing data. They include analyses that require the data to be missing
      completely at random; fixed-effects models and weighted generalized estimating
      equations, which require missing at random data; and a fully parametric approach
      where the outcomes and the missingness mechanism are jointly modelled, allowing
      non-ignorable missing data. The data show evidence of non-random missingness, but
      a formal test of non-ignorable missing data is not significant.

PMID- 9549821
TI  - Growth curve model analysis for quality of life data.
AB  - There is increasing interest in measuring health related quality of life in
      cancer clinical trials. Most quality of life data are measured repeatedly over a
      fixed time schedule to capture changes and to reflect relative advantages of
      study treatments. A multivariate repeated measures model is usually used to
      analyse this type of data. However, one of the difficulties of this analysis is
      that quality of life may be affected by the occurrence of some critical events
      experienced by patients. We may separate a patient's lifetime during study into
      different 'health states'. The duration of these health states may vary among
      patients, and may relate to the efficacy of the study treatment. In some cases
      quality of life data may be missing due to one of the many different types of
      missing data mechanisms specific for a health state. It is reasonable to assume
      that the missing data mechanism for a treatment arm is homogeneous within a
      defined health state, and to control for the potential confounding effect to
      appropriately assess the impact of treatment on the quality of life. In this
      paper, we propose a growth curve model conditional on a time-dependent variable
      of defined health states in order to assess the overall treatment effect while
      taking into account occurrences of missing data and measurements from irregular
      visits. A specific contrast can be drawn within the overall model for testing a
      specific hypothesis without relying on the analysis of subgroups of patients
      based on a smaller number of repeated measurements. Quality of life data from a
      recently completed small-cell lung cancer randomized trial are used to illustrate
      this method.

PMID- 9549823
TI  - Comparison of several model-based methods for analysing incomplete quality of
      life data in cancer clinical trials.
AB  - This paper considers five methods of analysis of longitudinal assessment of
      health related quality of life (QOL) in two clinical trials of cancer therapy.
      The primary difference in the two trials is the proportion of participants who
      experience disease progression or death during the period of QOL assessments. The
      sensitivity of estimation of parameters and hypothesis tests to the potential
      bias as a consequence of the assumptions of missing completely at random (MCAR),
      missing at random (MAR) and non-ignorable mechanisms are examined. The methods
      include complete case analysis (MCAR), mixed-effects models (MAR), a joint mixed
      effects and survival model and a pattern-mixture model. Complete case analysis
      overestimated QOL in both trials. In the adjuvant breast cancer trial, with 15
      per cent disease progression, estimates were consistent across the remaining four
      methods. In the advanced non-small-cell lung cancer trial, with 35 per cent
      mortality, estimates were sensitive to the missing data assumptions and methods
      of analysis.

PMID- 9549824
TI  - Cold snare excision is a safe method for diminutive colorectal polyps.
AB  - Cold snare excision (CSE) has proved to be an effective method for the
      destruction of diminutive polyps of the colon and rectum. We investigated the
      correlation between polyp size and bleeding time at the resected end after CSE,
      and also an appropriate measuring method using CSE. Eighty patients with single
      polyps were examined. Each polyp was identified as being 5 mm in diameter or
      smaller using the open-biopsy forceps technique (OBFT). The size of the polyp was
      calculated using our measuring system (SMS). Of the polyps identified as being 5
      mm in diameter or less using OBFT, 15% were 6 mm or more using the SMS. CSE was
      performed for each polyp, and the time taken for the hemostasis (bleeding time of
      the CSE; BTCSE) was determined. In seventy-seven polyps that were 6 mm or smaller
      in SMS, a correlation was noted between SMS and BTCSE. In three polyps that were
      7 mm or more by SMS, hemostasis took 10 min or more after CSE, and required
      electrocoagulation. These results suggest that CSE is a safe method for the
      removal of polyps determined to be 6 mm in diameter or smaller using the SMS.

PMID- 9549825
TI  - Polymorphism of short tandem repeat (STR) loci PLA2, D3S2459, D8S315 (kw38),
      CYP19, D3S1359, FGA, and D8S1132 in the Japanese and Chinese populations.
AB  - We report a study of polymorphism for seven short tandem repeat (STR) loci in
      Japanese and Chinese populations. Among 104 to 134 individuals in the both
      population samples, eight alleles were revealed for locus PLA2, thirteen for
      D3S1359, eleven for FGA, eight for D8S315 (kw38), ten for D8S1132, five for
      CYP19, and seven for D3S2459. They correspondingly constituted 10 to 39 genotypes
      therein. For most of the STRs, there was only a single allele active as the most
      frequent one among the others, except locus D3S1359 in Chinese samples (two
      alleles, 206 bp and 210 bp, frequency = 0.273 each). Also, the population
      genotype configurations were locus specific, varying in the patterns of commonest
      genotypes on each locus, e.g., one pattern for loci CYP19, D3S1359, and D8S315,
      one and two for loci PLA2 and D3S2459, two for locus D8S1132, and one and four
      for locus FGA. The distributions of observed genotypes were in Hardy-Weinberg
      Equilibrium. Furthermore, the seven STRs were exhibited highly polymorphic and
      informative for the both populations, and the alleles could be easily separated
      in electrophoresis and correctly interpreted with side-to-side allelic ladders.
      Together, the results suggest that the tri- and tetra-meric STRs are useful
      genetic markers for forensic practice.

PMID- 9549826
TI  - Capnometry as a tool to unmask silent pulmonary embolism.
AB  - Because pulmonary embolism is often silent, simple clinical procedures are
      desirable to identify patients with a low to intermediate probability of
      pulmonary embolism. Among 19,467 patients managed under general anesthesia, we
      had one bile tract surgery case and three neurosurgical cases whose silent
      pulmonary embolism was initially suggested by an increase in the arterial to end
      tidal CO2 gradient (from 17 to 27 mmHg) after general anesthesia was induced or
      their trachea was intubated. During the preoperative assessment, the patients
      presented no clinical manifestations suggestive of pulmonary embolism. Our
      initial diagnosis was confirmed by scintigraphy and/or angiography done
      immediately after the operations. Because capnometry has been shown to be
      applicable to non-intubated, spontaneously breathing patients, we suggest that
      measuring the gradient may serve as an additional method for unmasking silent
      pulmonary embolism in patients at risk or with disturbed consciousness, whether
      they are scheduled for operations or not.

PMID- 9549827
TI  - Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular
      resistance and fluid filtration coefficient in the perfused rat lung.
AB  - We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or
      cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability
      in isolated perfused rat lungs. Intraperitoneal injection of Salmonella
      enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance
      (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf)
      and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked
      endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with
      cGMP attenuated only the increase in Ra caused by endotoxin. Moreover,
      administration of db-cAMP 2 hours after endotoxin injection attenuated the
      increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight
      ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since
      the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by
      pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be
      useful to prevent acute pulmonary vascular injury.

PMID- 9549828
TI  - The effect of haloperidol on the histaminergic neuron system in the rat brain.
AB  - In this study, the effect of haloperidol on histamine (HA) levels, histidine
      decarboxylase (HDC) activities and the bindings of [3H]-(R)-alpha-methylhistamine
      ([3H]-(R)-alpha-MeHA) to histamine H3 receptors were investigated in the rat
      brain. Administration of 10 mg/kg of haloperidol decreased HA levels in the rat
      striatum and diencephalon, but increased HDC activities in rat striatum and
      diencephalon, although that of 5 mg/kg did not change them. Meanwhile,
      haloperidol inhibited the bindings of [3H]-(R)-alpha-MeHA to H3 receptor sites in
      the rat striatal membrane with a Ki value of 10.5 +/- 0.45 microM. These findings
      suggest that only a high dose of haloperidol increases HA synthesis and release
      as a histamine H3 receptor antagonist in the rat brain.

PMID- 9549829
TI  - A press-through-pack in the larynx.
AB  - A case of a 96-year-old male with a foreign body in the larynx is reported. The
      foreign body was a press-through-pack (PTP), a plastic packing for medicine, 16
      mm x 16 mm x 3 mm in size. The PTP was safely removed from the larynx under
      general anesthesia.

PMID- 9549830
TI  - Detection of minimal residual disease in cerebro-spinal fluid of a patient with
      acute myelogenous leukemia with t(16;21)(p11;q22) translocation by reverse
      transcriptase-polymerase chain reaction.
AB  - We describe a patient with acute myelogenous leukemia (AML) with
      t(16;21)(p11;q22) translocation, whose minimal residual disease (MRD) both in
      cerebrospinal fluid (CSF) and bone marrow (BM) was monitored by reverse
      transcriptase-polymerase chain reaction (RT-PCR). A TLS/ERG-FUS fusion
      transcript, which is known to be expressed by t(16;21)(p11;q22) translocation,
      was detectable by RT-PCR both in BM and CSF cells in the first complete
      remission, suggesting the existence of MRD. The disease relapsed 6 months after
      its onset and allogeneic peripheral blood stem cell transplantation (PBSCT) was
      undergone. A TLS/ERG-FUS fusion transcript became rapidly below the detection
      level after PBSCT. These findings suggest the usefulness of RT-PCR for the
      detection of MRD in CSF, which contains a limited number of cells, as well as BM.

PMID- 9549831
TI  - Paraparesis associated with mild congenital kyphoscoliosis in an adult.
AB  - A 48-year-old man suffering from paraparesis had congenital kyphoscoliosis due to
      fused wedged vertebrae between T2 and T4. The kyphoscoliosis consisted of left
      convex scoliosis measuring 26 degrees and kyphosis measuring 27 degrees. On CT
      myelograms and axial MR images, the dura and spinal cord were deviated
      anterolaterally to the concave side of the curve around its apex. The spinal cord
      was stuck and flattened against the posterolateral margin of the vertebral body
      to the base of the pedicle with the posterior subarachnoid space preserved.
      Anterior decompression from the concave side through a transthoracic approach
      resulted in a remarkable neurological improvement. The paraparesis may have been
      caused by compression of the spinal cord through a tethering effect due to its
      developmental tightness around the apical vertebra and the additional tension
      created by motions of the neck.

PMID- 9549832
TI  - Developmental fetal malformations: time to change terminology.

PMID- 9549833
TI  - Nitrovasodilators--will they be useful in lowering uterine artery resistance in
      pre-eclampsia and intrauterine growth restriction?

PMID- 9549835
TI  - The impact of fetal, maternal and external factors on prediction of the day of
      delivery by the use of ultrasound.
AB  - In a non-selected population comprising 15,241 women, an evaluation was performed
      of the impact of fetal, maternal and external factors on the ultrasonic
      measurement of the biparietal diameter (BPD) and the day of delivery. The 7824
      women who constituted the study population had singleton pregnancies and reliable
      menstrual histories, and they delivered spontaneously after 37 weeks. Multiple
      linear regression analysis was used. There was a difference in the size of the
      BPD at the ultrasound scan related to the gender, parity, maternal age,
      gestational age according to the last menstrual period and the experience of the
      operators. There was a total difference of +/- 1 day in the day of delivery as
      determined by ultrasound and the factors above. The effect on the day of delivery
      is explained by the differences in the BPD. An effect of gender on gestational
      length was present as well, which partly compensated for the difference in the
      BPD. In conclusion the accuracy of prediction of the day of delivery by
      ultrasound is influenced by the gender, parity, maternal age and the experience
      of the operator, but these differences are small and of no clinical importance.

PMID- 9549834
TI  - The effect of a nitric oxide donor on Doppler flow velocity waveforms in the
      uterine artery during the first trimester of pregnancy.
AB  - Our objectives were to study the effect of a nitric oxide donor on uterine blood
      flow velocity waveforms and maternal heart rate and blood pressure during the
      first trimester of pregnancy. Eleven women were examined at 8-12 weeks'
      gestation, prior to elective termination of pregnancy. Each woman was randomly
      given a sublingual tablet containing 5 mg of isosorbide dinitrate or placebo, on
      two consecutive days. Measurements of maternal blood pressure, heart rate and
      Doppler flow velocity waveforms of the ascending branch of the main uterine
      artery were obtained before, and every 2 min (for 20 min) after taking the drug
      or placebo. Following administration of isosorbide dinitrate, the mean arterial
      blood pressure fell from a control value of 82.5 +/- 5.6 mmHg to a nadir of 73 +/
      4.1 mmHg at 16 min (p < 0.0001). The mean maternal heart rate increased from a
      control value of 80.9 +/- 2.8 beats/min to a peak of 90.4 +/- 4.6 beats/min at 10
      min (p < 0.001). The mean resistance index in the uterine artery fell from a
      control value of 0.80 +/- 0.02 to a nadir of 0.73 +/- 0.03 at 10 min (p <
      0.0001). Analysis of covariance was employed to compensate for the effect of
      heart rate on the resistance index. The drug had a significant effect on the
      resistance index in the uterine artery, independent of maternal heart rate. These
      results suggest that drugs such as isosorbide dinitrate may have a potential
      benefit under such conditions where the production of nitric oxide (i.e.
      endothelium-derived relaxing factor) is decreased.

PMID- 9549836
TI  - Pregnancy outcome among non-participants in a trial on ultrasound screening.
AB  - Our objective was to characterize and evaluate pregnancy outcome in women who
      declined participation in a trial on ultrasound screening in the second
      trimester. Between 1985 and 1987, 8768 women were recruited for a trial on
      ultrasound screening. By randomization, 4997 women were assigned to either a
      screening or a non-screening group. Of the 1414 excluded women, data were
      retrieved from 1211 (86%). Participation was declined by 526 of these 1211 women,
      either because of anxiety regarding harmful effects of ultrasound or because they
      could see no benefits of ultrasound scanning. Non-participants and participants
      were compared. The non-participants were older, had a higher birth/pregnancy
      ratio, were less often smokers, and had fewer ultrasound examinations than the
      participants. There was a longer mean pregnancy length, an increased number of
      post-term deliveries, more suspicions of small-for-gestational-age fetuses and
      later detections of multiple pregnancies among non-participants as compared with
      the screening group. No differences in neonatal morbidity were found except for a
      greater number of mild respiratory disorders in the non-participant group. The
      non-participant women were more obstetrically experienced and showed indications
      of a healthier lifestyle in comparison with participants. The differences found
      in pregnancy outcome could be explained by the ultrasound screening procedure.
      There were no major differences in neonatal morbidity between the groups.

PMID- 9549837
TI  - Conditional centiles for the quantification of fetal growth.
AB  - A total of 274 low-risk pregnancies underwent predetermined, scheduled, serial
      ultrasound examinations and measurement of the biparietal diameter, fetal
      abdominal area, femur length and estimated fetal weight. The longitudinal nature
      of this dataset permits the construction of conditional centiles for these
      measurements, whereby the dimensions of an individual fetus at a given
      gestational age can be extrapolated to give a range of expected values (expressed
      as centiles) at a later gestational age. Examples of conditional centiles based
      upon 4-week measurement separations are presented. These conditional centiles
      permit the appropriate quantification and subsequent evaluation of time-dependent
      changes in fetal dimensions to be made.

PMID- 9549838
TI  - Normal fetal thyroid volume.
AB  - A prospective study of 289 normal fetal thyroids was undertaken between 20 and 36
      weeks of gestation in 289 mothers without any history of thyroid disease or
      maternal disease that could cause intrauterine growth restriction. The fetal
      thyroid volume was calculated by the ellipsoid equation, with the assumption that
      each lobe was an ellipse. A nomogram relating fetal thyroid volume to gestational
      age was established. The mean fetal thyroid volume was found to be 0.23 +/- 0.18
      cm3 (median 0.17 cm3; range 0.022-0.85 cm3). The ratio of fetal thyroid volume to
      estimated fetal weight (V/W ratio) (at 0.163 +/- 0.079 cm3/kg) was constant
      throughout gestation. The value was smaller than those of the child and the adult
      reported in other studies, indicating that fetal thyroid enlargement is likely to
      be underestimated if based on postnatal criteria. It was found that the mean
      fetal thyroid volume was significantly correlated with estimated fetal weight and
      gestational age, in which the former dominated the effect. The fetal thyroid
      increased in size much faster after 32 weeks, suggesting that evaluation of
      possible fetal goiter should take into account gestational age and the nomogram
      developed in this study.

PMID- 9549839
TI  - Psychological outcomes following missed abortions and provision of follow-up
      care.
AB  - This cross-sectional study of 204 women who had experienced a missed abortion,
      diagnosed at 10-14 weeks of pregnancy, examined the availability and desirability
      of routine follow-up care, and whether such care is associated with reduced
      psychological morbidity in the aftermath of miscarriage. Clinically elevated
      anxiety and depression were observed in 45% and 15% of women, respectively, and
      the mean score of grief was 2.52 which is similar to that observed in people who
      suffer death of a close relative. A follow-up appointment after the miscarriage
      was thought to have been desirable by 92% of women but was offered to only 30%.
      No significant association between such care and reduced psychological morbidity
      was identified. However, there were significantly more women with clinically
      elevated levels of anxiety among those who felt that they were not provided with
      an opportunity to discuss their feelings during the follow-up, suggesting that
      such a follow-up either had a deleterious effect on women's psychological state
      or the distress itself led to such a perception of care. One-third of women in
      our sample would have liked psychological counselling to help them deal with the
      emotional aspects of their loss.

PMID- 9549840
TI  - Unexpected effect of a nitric oxide donor on uterine artery Doppler velocimetry
      in oligomenorrheic women with polycystic ovaries.
AB  - We compared uterine artery vascular responses following administration of the
      nitric oxide donor glyceryl trinitrate to ten women with oligomenorrhea and
      ultrasound evidence of polycystic ovaries with those of nine women with a normal
      menstrual cycle and ultrasonically normal ovaries. Mean arterial blood pressure,
      pulse rate and uterine artery flow velocity waveforms were recorded before and 60
      75 min after glyceryl trinitrate patch application. The pulsatility index and
      resistance index were calculated to describe changes in impedance to flow in the
      uterine artery. Peak systolic and time-averaged velocities were also measured.
      Pretreatment median arterial pressure was higher in women with polycystic ovaries
      (90 mmHg) compared to those with regular cycles (80 mmHg) (p < 0.05). No
      differences were found in pulse rate and uterine artery blood flow indices
      between the two groups. After glyceryl trinitrate patch administration, there was
      no change in blood pressure or pulse rate in either group. In women with
      polycystic ovaries, there was an increase in uterine artery resistance index
      (0.93 to 1.00; p < 0.05) and pulsatility index (3.77 to 4.99; p < 0.05) and a
      decrease in peak systolic (36.8 to 32.3 cm/s; p < 0.05) and time-averaged maximum
      (8.5 to 5.0 cm/s; p < 0.05) velocities. Uterine artery Doppler parameters
      remained unchanged in women with normal cycles. Uterine artery vascular responses
      to the nitric oxide donor glyceryl trinitrate are different in women with normal
      cycles compared to oligomenorrheic women with polycystic ovaries. This may be
      relevant to an understanding of the pathophysiology underlying the higher risk of
      cardiovascular morbidity and mortality associated with polycystic ovarian
      syndrome.

PMID- 9549841
TI  - 3D Color Power Angio imaging: a new method to assess intracervical
      vascularization in benign and pathological conditions.
AB  - It is well known that angiogenesis is a fundamental event in the growth of tumors
      as well as in physiological conditions. In an ongoing prospective study involving
      eight women, we investigated the microvasculature within the cervix by the use of
      3D Color Power Angio imaging. The ultrasound equipment was used in conjunction
      with specialized software providing high-resolution '3D-Angiomode'. The system
      provides the ability to visualize blood flow in small vessels that are
      undetectable by conventional color Doppler techniques and also to study the
      architecture and determine the number of blood vessels. Comparison of the vessels
      in the normal cervix with those in the cervix affected by carcinoma or bacterial
      or viral infection demonstrated that, in malignant tissue, there is a chaotic
      network of tortuous vessels traversing the tumor mass, whereas, in benign tissue
      or tissue that is inflamed as a result of infection, the course of the vessels
      has a regular structure.

PMID- 9549842
TI  - The upper neck pouch sign: a prenatal sonographic marker for esophageal atresia.
AB  - Prenatal suspicion of esophageal atresia is usually based on the finding of a
      small or absent fetal stomach in association with polyhydramnios. As similar
      findings may be generated by other abnormalities, confirmation of the diagnosis
      is generally not possible until birth. We present a case in which the suspicion
      of esophageal atresia was raised in the 22nd week of pregnancy in the presence of
      a small stomach bubble associated with a persistent left superior vena cava. The
      diagnosis was confirmed 4 weeks later by direct visualization of the fluid-filled
      blind-ending esophagus during fetal swallowing, which we called the upper neck
      pouch sign. This is the first case in which the onset of this sonographic entity
      was specifically observed on serially repeated sonograms as early as the 22nd
      week. The appearance of this direct sign of esophageal atresia is described, and
      the literature is reviewed.

PMID- 9549843
TI  - Prenatal diagnosis and perinatal management of a lingual lymphangioma.
AB  - We describe the prenatal ultrasonographic features that led to the diagnosis of a
      lingual lymphangioma. The risk of upper airway obstruction, which is associated
      with this rare abnormality, prompted us to plan careful perinatal management. We
      believe that, in cases of suspected lymphangioma of the tongue or other
      oropharyngeal tumors, elective delivery should be carried out in a tertiary
      referral center in which emergency ventilation and tracheostomy are possible.

PMID- 9549845
TI  - Antenatal diagnosis and management of a ranula.
AB  - We describe a case of congenital ranula or retention salivary cyst diagnosed at
      26 weeks of gestation. The fetal karyotype was obtained by amniocentesis and
      chorionic villus sampling, and was normal. Follow-up ultrasound scans revealed no
      changes in the size or the position of the cyst. Surgical treatment was performed
      2 days after a normal vaginal delivery, with excellent results.

PMID- 9549844
TI  - Prenatal diagnosis of congenital granular cell epulis.
AB  - Congenital granular epulis is a benign tumor that has rarely been diagnosed
      prenatally, although there have been numerous reports on its postnatal diagnosis.
      We report a case of large granular epulis diagnosed at 31 weeks' gestation in a
      woman whose previous anomaly scan had been normal. The lesion was 2.5 cm in
      diameter, pedunculated, and arose from the maxilla. It was completely surgically
      removed following preterm vaginal birth and histologically examined. The tumor
      did not prevent deglutition of the amniotic fluid and did not interfere with
      feeding or respiration, but prevented complete closure of the lips. We discuss
      the fetal management and the theories of histogenesis, and highlight the
      importance of early diagnosis and treatment.

PMID- 9549846
TI  - Prenatal ultrasound observations in subsequent pregnancies with Perlman syndrome.
AB  - Perlman syndrome is a rare disease with a poor prognosis. Until now, the specific
      antenatal diagnostic criteria of this syndrome have not been documented. We
      report on two pregnancies with Perlman syndrome, in the same woman, in which
      karyotyping and ultrasound examination were performed. In the first pregnancy,
      the final diagnosis was made only postnatally, whereas, in the second affected
      pregnancy, nuchal translucency was seen at 11 weeks. From 23 weeks onwards the
      classical signs of renal and abdominal enlargement were observed. The impact of
      non-specific early ultrasound markers on decision-making in pregnancies with
      family risks, where specific tests are not yet available, must be evaluated.

PMID- 9549847
TI  - Hydronephrotic pelvic kidney mimicking an ovarian cyst.

PMID- 9549848
TI  - Sonographic differential diagnosis of persistent ovarian cysts.

PMID- 9549849
TI  - Fetal hydrometrocolpos: not only diagnostic but also therapeutic dilemmas.

PMID- 9549850
TI  - Serological evidence of morbillivirus infection in small cetaceans from the
      Southeast Pacific.
AB  - The presence of morbillivirus-specific serum antibodies was examined by an
      indirect enzyme linked immunosorbent assay (iELISA) and virus neutralization
      tests in serum samples from 30 dusky dolphins (Lagenorhynchus obscurus), 8 long
      snouted common dolphins (Delphinus capensis), 2 inshore and 6 offshore bottlenose
      dolphins (Tursiops truncatus) and 20 Burmeister's porpoises (Phocoena
      spinipinnis) taken in fisheries off central Peru in 1993-1995. The sera from six
      dusky dolphins, one common dolphin and three offshore bottlenose dolphins were
      positive on a coat of dolphin morbillivirus (DMV) antigen in the iELISA. Several
      of these sera were also positive when tested against peste des petits ruminants
      and rinderpest virus antigen. Porpoise morbillivirus and/or DMV neutralizing
      antibodies were detected in the sera of two bottlenose and three dusky dolphins
      that reacted positively with DMV antigen in iELISA and also in the sera of one
      common, one dusky and one bottlenose dolphin that were negative in the iELISA.
      These results strongly suggest that viruses closely related, or identical, to the
      cetacean morbillivirus present in the North Atlantic and the Mediterranean Sea
      infect several species of Delphinidae of the Southeastern Pacific. No convincing
      morbillivirus-specific antibody positive reactions were detected in the sera from
      either the Burmeister's porpoises or the inshore bottlenose dolphins.

PMID- 9549851
TI  - A nested PCR for detection of North American isolates of bluetongue virus based
      on NS1 genome sequence analysis of BTV-17.
AB  - A nested polymerase chain reaction (PCR)-based assay, for detection of bluetongue
      virus (BTV) ribonucleic acid in cell culture and tissue samples, was developed.
      Two pairs of oligonucleotide primers (BTV1 and BTV4 and BTV2 and BTV3), selected
      from non-structural protein 1 (NS1) gene of BTV-17, were used for the nested PCR
      in two amplification steps. First a 826-bp product was amplified using an outer
      primer pair BTV1 and BTV4. The second amplification, using nested or internal
      primer pair BTV2 and BTV3, produced a 517-bp PCR product. RNA from North American
      prototype serotypes 2, 10, 11, 13 and 17, propagated in cell cultures, were
      detected by this nested PCR-based assay. The nested primers BTV2 and BTV3
      increased the sensitivity of the BTV PCR assay, and as little as 0.1 fg of BTV
      RNA (equivalent to 5 viral particles) could be detected. Amplification products
      were not detected when the PCR-based assay was applied to RNA from a closely
      related orbivirus, epizootic hemorrhagic disease virus (EHDV) prototype serotypes
      1 and 2; total nucleic acid extracts from uninfected BHK-21 cells; or whole blood
      from calves and deer that were BTV-seronegative and virus isolation negative.
      Application of this nested BTV PCR-based assay to clinical samples resulted in
      detection of BTV RNA from a variety of tissues collected from calves and deer
      with natural and experimental BTV infections. The described BTV PCR-based assay
      provides a valuable tool to study the epidemiology of BTV infection in
      susceptible wild ruminants and domestic livestock.

PMID- 9549853
TI  - Iron-regulated outer membrane proteins of Pasteurella multocida and their role in
      immunity.

PMID- 9549852
TI  - Humoral and bronchial immune responses in cattle experimentally infected with
      Mycoplasma mycoides subsp. mycoides small colony type.
AB  - The course of immune reactions of the manifold antigens of Mycoplasma mycoides
      subsp. mycoides small colony type (SC) was analysed in serum and bronchial lavage
      of cattle experimentally infected with the African strain Afade and the European
      strain L2 using Western-blots and complement fixation. Western-blot analysis of
      total antigens of both strains with sera from animals infected with the
      homologous and heterologous strain revealed the common dominant immunogenic
      antigens with the molecular masses of 110, 95, 85, 80, 72, 62, 48 and 39 kDa. The
      sequential sampling of the blood and bronchial lavages before and after contact
      infections allowed us to identify the antigens of 85, 80, 72, 48 and 39 kDa as
      particularly early immunogens. The IgA Western blots of the bronchial lavages
      showed distinct, early and persistent reactions to the 110, 85, 80, 72, 48 and 45
      kDa proteins. These proteins were the predominant lipoproteins as determined by
      [14C]palmitic acid labelling. Only relatively weak reactions of the bronchial
      lavages were detected with IgG. In general immune responses were significantly
      stronger in the animals infected with the African strain Afade, which gave
      positive results two weeks after contact infection. In contrast, the animals
      infected with the European strain L2 induced much lower reactions with a delay of
      three months after contact infection. In one animal strain L2 caused no sero
      conversion and no infection. The results indicate a difference in virulence
      between the African strain Afade and the European strain L2.

PMID- 9549854
TI  - Exoprotein and slime production by coagulase-negative staphylococci isolated from
      goats' milk.
AB  - Milk from mastitis-free goats from French herds was examined for the presence of
      coagulase-negative staphylococci (CNS), and 165 positive isolates were evaluated
      for their capacity to produce exoproteins. Most isolates were identified as
      Staphylococcus caprae (N = 91) or S. xylosus (N = 36), but members of at least
      nine other species were present. Overall, some 57% of isolates produced toxins
      with phenotypic properties of alpha-hemolysin, and 75% produced toxins resembling
      S. aureus beta and/or delta-hemolysins. Thermostable desoxyribonuclease (TNAse)
      was secreted by 29% of isolates and thermolabile DNAse by 66%. Slime was produced
      by 42% of our cultures and, although none of them showed activity to insoluble
      elastase, over 70% lysed the soluble substrate. No clinical consequences were
      observed to correlate with exoprotein production, which proved to be inconstant
      within individual CNS species.

PMID- 9549855
TI  - Isolation of Actinobacillus equuli from the oral cavity of healthy horses and
      comparison of isolates by restriction enzyme digestion and pulsed-field gel
      electrophoresis.
AB  - Swab samples were collected from the oral cavity of 174 horses in 10 farms and
      cultured selectively for Actinobacillus equuli. A. equuli could be isolated from
      37% of all samples, varying between 12 and 88% in the different farms. Eight
      horses were sampled repeatedly for several days, with a variation in isolation
      frequency between 50 and 88%. Isolates were compared by restriction enzyme
      digestion and Pulsed-Field Gel Electrophoresis. A high degree of strain
      variability was found within each horse population as well as some variability
      over time between strains isolated from the same horse.

PMID- 9549857
TI  - Restriction endonuclease analysis and plasmid profiling of Actinobacillus
      pleuropneumoniae serotype 7 strains.
AB  - Seventeen serotype 7 Actinobacillus pleuropneumoniae strains isolated in New
      Zealand and A. pleuropneumoniae serotypes 1-12 reference strains were typed by
      restriction endonuclease analysis of chromosomal DNA and plasmid profiling. All
      serotype 7 strains produced similar DNA cleavage patterns and were significantly
      different to other reference serotype strains. Minor differences in the cleavage
      patterns enabled the 17 serotype 7 strains to be grouped into seven profiles.
      Plasmids were identified in all but three strains but the banding patterns did
      not account for the differences in the chromosomal profiles. The study showed
      that restriction endonuclease analysis and plasmid profiling are useful in
      epidemiological studies of porcine pleuropneumonia.

PMID- 9549856
TI  - Characterisation of epitopes of type 1 fimbriae of Salmonella using monoclonal
      antibodies specific for SEF21 fimbriae of Salmonella enteritidis.
AB  - Monoclonal antibodies (mAbs) were used to identify and characterise epitopes of
      type 1 (SEF21) fimbriae of Salmonella enteritidis. The distribution of the
      epitopes among salmonellas and other enterobacteria was investigated, as well as
      the influence of growth media and temperatures on their expression. At least four
      different epitope clusters were identified on SEF21 fimbriae of S. enteritidis.
      Two of these clusters were associated with fimbrial haemagglutinins that were
      either common to all salmonellae tested, or restricted only to S. enteritidis and
      S. dublin. The four epitope clusters were identified on type 1 fimbriae of most
      Salmonella serotypes, as well as non-haemagglutinating type 2 fimbriae of S.
      pullorum and S. gallinarum, and on many other enterobacterial species. The
      expression of the epitopes was affected by growth conditions.

PMID- 9549858
TI  - Distribution and characterization of faecal necrotoxigenic Escherichia coli CNF1+
      and CNF2+ isolated from healthy cows and calves.
AB  - Faecal swabs obtained from a random sample of 268 cows and 90 calves on 19 Lugo
      (northwestern Spain) farms were examined for necrotoxigenic Escherichia coli
      (NTEC) producing the cytotoxic necrotizing factors type 1 (CNF1) and type 2
      (CNF2). We found NTEC CNF1+ and CNF2+ on 11% and 95% of the farms, respectively,
      NTEC producing CNF2 were significantly more frequently isolated from calves (58%)
      than from cows (17%) (P < 0.001). The proportion of animals colonized with CNF2+
      strains on each farm ranged from 0% to 60%. NTEC strains producing CNF2 isolated
      from healthy cattle belonged to 27 O serogroups; however, 64% were of one of 12
      serogroups (O2, O8, O8-O75, O14, O15, O55, O86, O88, O115, O121, O147, and O168).
      Furthermore, the serogroups determined in CNF2+ strains isolated from cows (O2,
      O8, and O14) were different from those found in NTEC producing CNF2 isolated from
      calves (O8-O75, O15, O55, O86, O88, O115 and O147).

PMID- 9549859
TI  - The effects of inoculation of Listeria monocytogenes into the ovine mammary
      gland.
AB  - In each of two experiments, the effects of inoculation of Listeria monocytogenes
      into the ovine mammary gland were studied. In the first experiment, ewes were
      challenged with one or other of five different Listeria spp. isolates to study
      differences in their pathogenicity. In the second, ewes were challenged with L.
      monocytogenes serotype 1/2a to study the sequential features of the infection.
      The reaction of the mammary glands was assessed by bacteriological, cytological
      and histological methods. No distinct variation in the pathogenicity of L.
      monocytogenes isolates was evident: all produced subclinical mastitis,
      independently of their origin or serotype; a L. innocua isolate caused only a
      transient increase of milk somatic cell counts. After challenge, L. monocytogenes
      was isolated for 88 days from the milk of inoculated glands, whose milk somatic
      cell counts were greater than 1.0 x 10(6) cells ml-1. The organism was also
      isolated from the mammary lymph nodes, but not from any internal organ of any
      inoculated ewe. In early stages of the infection neutrophilic infiltration was
      the predominant histological feature, but hyperaemia, and degeneration of
      alveolar epithelial cells were also recorded. Later, chronic inflammatory
      features predominated, with lymphocytes as the principal cell types, destruction
      of alveoli and fibrous tissue proliferation. In the final stage of the
      experiment, fibrosis was the salient finding. It is concluded that L.
      monocytogenes can cause subclinical mastitis after intramammary inoculation into
      ewes.

PMID- 9549860
TI  - Multiple receptors on porcine intestinal epithelial cells for the three variants
      of Escherichia coli K88 fimbrial adhesin.
AB  - We evaluated intestinal epithelial membrane preparations from five phenotypes of
      pigs, distinguished by the variant of K88 fimbrial adhesin (K88ab, K88ac, K88ad)
      which bind to their intestinal epithelial cells (A-all three variants, B-K88ab
      and K88ac, C-K88ab and K88ad, D-K88ad, and E-none of the variants), for the
      presence of K88 adhesin receptors. Intestinal brush border membranes were
      prepared from 20 animals (four from each phenotype). Brush border proteins, that
      had been separated using SDS-PAGE and transferred to nitrocellulose membranes,
      were overlaid with biotinylated K88 adhesin, 35S-labelled K88+ Escherichia coli,
      or biotinylated K88+ E. coli. Biotinylated K88ab and K88ac fimbrial adhesins and
      labelled E. coli expressing K88ab or K88ac adhesin bound to 210- and 240-kDa
      receptors in phenotype A and B, but not phenotype C, D, or E animals. In
      contrast, no phenotype-specific receptors were identified for the K88ad adhesin.
      Previously, purified K88ab and K88ac fimbriae were shown to block K88ad binding,
      but purified K88ad fimbriae were unable to block K88ab or K88ac binding in
      phenotype A animals. These results point to the existence of three K88 adhesin
      receptors to account for the observed phenotypes: (1) Receptor bcd binds all
      three variants and is found in phenotype A pigs, (2) Receptor bc (210- and 240
      kDa receptors) binds K88ab and K88ac and is found in phenotype A and B pigs, and
      (3) Receptor d binds K88ad and is found in phenotype C and D pigs.

PMID- 9549862
TI  - Phenotypic and genotypic variation of feline calicivirus during persistent
      infection of cats.
AB  - Amino acid sequence of the capsid protein hypervariable region of nine feline
      calicivirus (FCV) isolates recovered from cats persistently infected after
      inoculation with the FCV strain 255 parent virus is reported. Capsid proteins
      from all the isolates were highly cross reactive by Western blot analysis using
      polyclonal antisera to FCV. Reverse-transcription PCR was used to obtain sequence
      information of the FCV capsid protein highly variable E region. Amino acid
      substitutions occurred between residues 426 and 458 of the FCV capsid protein E
      region. The sequence data and phylogenetic reconstructions based on the sequence
      information correlated well with antigenic differences among isolates determined
      by two-way cross neutralization. These results agree with previous reports using
      divergent isolates of FCV that correlated amino acid differences with serology.
      This further supports the hypothesis that the FCV capsid protein E region from
      residues 426 to 458 contains the serotypic determinants of FCV important to
      antigenic variation.

PMID- 9549861
TI  - Characterization of an immuno-dominant antigen in Brucella ovis and evaluation of
      its use in an enzyme-linked immunosorbent assay.
AB  - A panel of 45 Brucella ovis serologically positive sera were tested in
      immunoblots against B. ovis outer membrane proteins Omp31 and Omp25, purified by
      preparative SDS-gel electrophoresis. Forty-three sera reacted with Omp31, while
      only 11 reacted with Omp25, suggesting that Omp31 is identical to the previously
      reported immuno-dominant 29-kDa protein. Attempts to purify Omp31 on a larger
      scale by using procedures such as ion exchange-, reversed phase-, affinity- and
      gel filtration chromatography suggested that the outer membrane proteins were
      aggregated with rough lipopolysaccharide. Only denaturing SDS-gel filtration
      chromatography was able to separate proteins of about 29 kDa from rough
      lipopolysaccharide but did not separate Omp31 from Omp25 in B. ovis preparations.
      When used in an enzyme-linked immunosorbent assay, this 29-kDa protein
      preparation was less sensitive and less specific than the routinely used heat
      extracted B. ovis antigen. A readily available recombinant E. coli, expressing
      the gene for Omp31 from Brucella melitensis 16 M, was used to extract and enrich
      recombinant Omp31 by a temperature-dependent Triton X-114-based technique. When
      this material was used in immunoblots with the 45 sera from B. ovis-infected
      sheep and with 10 monoclonal antibodies, raised against B. ovis Omp31, major
      differences in the antibody reactivity between the recombinant B. melitensis
      Omp31 and the B. ovis Omp31 were found. Such differences were unexpected because
      of the known structural and immunological relatedness of outer membrane proteins
      from various Brucella species. These results indicated that the antibody-response
      in B. ovis naturally-infected sheep against the immuno-dominant Omp31 was
      directed against epitopes which were only accessible when the protein was
      aggregated with rough lipopolysaccharides, or which were formed after aggregation
      but were not present in the recombinant protein.

PMID- 9549863
TI  - Molecular analysis of the nucleocapsid protein of recent isolates of canine
      distemper virus in Japan.
AB  - We analyzed the molecular properties of the nucleocapsid protein (NP) of canine
      distemper viruses (CDV), isolated between 1992 and 1995 in Japan. Four CDV field
      isolates (Yanaka, Ueno, Hamamatsu, and Adachi strains) obtained were
      antigenically identical. Sequence analysis of entire region of the NP gene of a
      field isolate, the Yanaka strain, revealed that the NP gene contained 1683
      nucleotides and was 93.2% homologous with a laboratory strain, the Onderstepoort
      strain. The deduced amino acid sequence contained 523 amino acids and was 95.2
      and 99% homologous with those of the Onderstepoort and a virulent strain, A75/17
      strain, respectively. Since most of the diversities in amino acid sequence
      occurred in two domains, at the N'- and the C'- termini, we further sequenced 3'
      terminal regions of the remaining three field isolates. Based on the sequences,
      the new CDV isolates had one cluster that distinguished them from the laboratory
      strain.

PMID- 9549865
TI  - Exploratory study on the economic value of a closed farming system on Dutch dairy
      farms.
AB  - A closed farming system may prevent the introduction of infectious diseases on to
      dairy farms and could be a good starting point for the eradication of these
      diseases. In order to introduce a closed farming system, farmers need to be made
      aware of how these diseases are introduced into the herd. Farmers will be more
      likely to implement a closed farming system when the economic value is quantified
      and attractive. An exploratory study was carried out to investigate the technical
      and economic results of closed dairy farms. Farms that purchased cattle and/or
      shared pasture (defined as 'open' farms) differed in technical results from farms
      that did not ('closed' farms). The results of the discriminant analysis showed
      that the 'closed' farms incurred lower costs for veterinary services, had a lower
      average age at first calving and a higher birth rate per 100 dairy cows. A linear
      regression analysis was carried out to investigate the influence of the farming
      system on economic performance. Being 'closed' was found to increase the net
      profit by 0.31 Pound per 100 kg of milk, or approximately 25 Pounds per cow per
      year or 5 per cent of the typical net return to labour and management (1 Pound =
      Dfl 2.80 in November 1996).

PMID- 9549864
TI  - Investigations into field cases of porcine colitis with particular reference to
      infection with Serpulina pilosicoli.
AB  - Investigations into the possible causes of colitis and typhlocolitis were carried
      out on 85 pig units in the United Kingdom between 1992 and 1996. Serpulina
      pilosicoli was identified most commonly, occurring as the suggested primary agent
      on 21 (25 per cent) of the units but forming part of mixed infections on another
      23 (27 per cent) of the units, the main co-infections being Yersinia
      pseudotuberculosis (eight units), proliferative enteropathy (six units),
      Salmonella species (four units) or Serpulina hyodysenteriae (two units).
      'Atypical' Serpulina species, S hyodysenteriae, Salmonella typhimurium, Y
      pseudotuberculosis and Lawsonia intracellularis (proliferative enteropathy) were
      the suggested primary agents on seven, six, four, four and three units,
      respectively. Various combinations of mixed infections involving the latter
      organisms and other possibly incidental agents were recorded on another 10 units.
      Investigations on a further six units failed to detect any recognised pathogens.
      On units where S pilosicoli was the suggested primary agent, pigs ranging between
      20 to 40 kg (eight to 16 weeks of age), but occasionally up to 50 kg, had
      diarrhoea and grew poorly over a period of two to three weeks. The prevalence was
      estimated to be between 5 and 15 per cent in affected batches, with a mortality
      of approximately 1 per cent. The clinical signs usually developed seven to 14
      days after the moving and mixing of pigs. At postmortem examination, affected
      pigs had liquid contents in their colon, which contained accumulations of mucus
      in some chronic cases. Gross and histological lesions of colitis were prominent
      in the mid-spiral region of the colon. In mixed infections with Y
      pseudotuberculosis, Salmonella typhimurium or S hyodysenteriae, lesions were more
      extensive and affected the caecum as well as the colon. In the colon, lesions of
      proliferative enteropathy were usually confined to the proximal half of the
      ascending spiral but mixed infection with S pilosicoli caused more extensive
      colitis. Mixed infections were reported to prolong the time taken for pigs to
      recover naturally and to have a more detrimental effect on growth rates than S
      pilosicoli infection alone. Despite the successful treatment of batches of pigs
      with tiamulin or lincomycin, S pilosicoli infection persisted as a chronic
      problem on many units, with diarrhoea and colitis in successive batches of pigs
      unless prophylactic medication was used.

PMID- 9549866
TI  - Effect of hoof characteristics on the propensity of cattle to slip.
AB  - Bovine hooves were assessed for their linear and volumetric characteristics and
      ranked in sets of four for hoof volume. An artificial cow was constructed with
      the hooves set into metal cylinders underneath a platform containing a known
      weight. The device was connected via a strain gauge to a pulling handle operated
      by two people, and the horizontal force required to move each set of hooves was
      determined three times. The coefficient of friction, calculated as the horizontal
      force divided by the fixed vertical force, was positively correlated with hoof
      volume. The same exercise was repeated with the hooves ranked for toe angle, and
      the hooves with steep toe angles had a lower coefficient of friction than the
      hooves with shallow toe angles. However, since both hoof volume and toe angle
      were related to toe length, the relationship between friction and toe angle was
      believed to derive from the larger size of claws with shallow toe angles. The
      results indicate that young cattle that have small claws with smooth surfaces and
      steep toe angles are more likely to slip.

PMID- 9549867
TI  - A neuronal vacuolar disorder in young rottweiler dogs.
AB  - Four rottweiler pups from two litters developed severe progressive signs of
      spinal ataxia, cerebellar ataxia and tetraparesis/paralysis. The signs started
      with ataxia of the pelvic limbs at seven to eight weeks of age and progressed to
      tetraparesis and paralysis within three to five weeks. Postmortem, a vacuolar
      neuronal disorder was found in the cerebellum, brainstem and the spinal cord,
      associated with Wallerian type degeneration in the brainstem, cerebellar
      peduncles and the medullary cord. Electron microscopy revealed empty membrane
      bound vacuoles. Immunohistochemistry for PrPSc was negative. The disorder differs
      clinically and pathologically from other neurological disorders in the breed and
      a new (familial) neurological disorder in the rottweiler is suspected.

PMID- 9549868
TI  - Metastatic melanoma causing spinal cord compression in a horse.

PMID- 9549869
TI  - Anthropogenic mortality of the common toad (Bufo bufo) in Scotland.

PMID- 9549870
TI  - Segmental aplasia of the epididymis in a Siberian husky.

PMID- 9549871
TI  - Primary bronchiolo-alveolar adenocarcinoma in a dromedary camel (Camelus
      dromedarius).

PMID- 9549872
TI  - Ciprofloxacin-resistant Salmonella typhimurium DT104.

PMID- 9549873
TI  - Ivermectin-resistant Cooperia species from calves on a farm in Somerset.

PMID- 9549874
TI  - 'Stray voltage' and sudden collapse in horses and cattle.

PMID- 9549875
TI  - 'Stray voltage' and sudden collapse in horses and cattle.

PMID- 9549876
TI  - Role of paraprofessionals in practice.

PMID- 9549877
TI  - Child sexual abuse evaluations: the scientist-practitioner model.
AB  - The scientist-practitioner model is presented as a format for conducting child
      sexual abuse evaluations. This model bases conclusions on empirically established
      relationships between data and the behavior of interest, rather than on
      subjective opinions. Using empirically derived evidence, the scientist
      practitioner defines child sexual abuse as a life event rather than a clinical
      syndrome, relies on base rates of behavior for distinguishing and understanding
      differences between nonsexually abused and sexually abused children, and
      considers issues of instrument sensitivity and specificity when utilizing
      assessment tools in child sexual abuse evaluations. This model enlists safeguards
      to keep the evaluator from inappropriately forming cause and effect associations
      between a child's single response (e.g., behavioral and emotional symptoms,
      interactions with anatomically detailed dolls, drawing genitalia) and the
      occurrence of an event (e.g., sexual abuse).

PMID- 9549878
TI  - The assessment of child sexual abuse allegations: using research to guide
      clinical decision making.
AB  - As reports of child sexual abuse (CSA) have risen, greater attention has been
      focused on how clinicians evaluate allegations of abuse. A common theme in the
      CSA assessment literature is to encourage comprehensive, multimodal assessments.
      This recommendation, however, is rarely accompanied by suggestions regarding how
      clinicians might integrate and differentially weight the information gathered.
      The present article is designed to address the issue of which sources of
      information clinicians should rely upon when conducting CSA assessments.
      Specifically, the commonly used indicators and procedures for assessing
      allegations of abuse are identified and then examined in light of their
      respective empirical literatures. It is concluded that medical examinations and
      the child's report are among the best sources of information, and should
      therefore be most heavily relied upon to arrive at accurate decisions. Clinicians
      are encouraged to adopt the mind set of a scientist conducting an a priori,
      hypothesis-driven research investigation. This approach should help clinicians
      avoid the temptation of post hoc analyses that reflect personal biases more than
      the actual data.

PMID- 9549879
TI  - An analysis of competency to stand trial: an integration of case law and clinical
      knowledge.
AB  - In the past three decades competency to stand trial has emerged as a central
      issue in mental health law and forensic psychology. This article combines legal
      and clinical frameworks for a more integrated understanding of competency to
      stand trial. The legal framework focuses on Supreme Court decisions beginning
      with Dusky and reviews several legal theories of competence. The empirical
      framework is investigated within Grisso's (1986) conceptualization of legal
      competencies. In addition, the efficacy of specialized forensic assessments is
      evaluated, including the newly developed MacArthur Structured Assessment of the
      Competencies of Criminal Defendants (MacSAC-CD). The article concludes with
      observations of competency as a construct and their implications for forensic
      practice.

PMID- 9549880
TI  - Integrating base rate data in violence risk assessments at capital sentencing.
AB  - Prediction of violence in capital sentencing has been controversial. In the
      absence of a scientific basis for risk assessment, mental health professionals
      offering opinions in the capital sentencing context are prone to errors.
      Actuarial or group statistical data, known as base rates, have proven far
      superior to other methods for reducing predictive errors in many contexts,
      including risk assessment. Actuarial follow-up data on violent recidivism of
      capital murderers in prison and post release have been compiled and analyzed to
      demonstrate available base rates for use by mental health experts conducting risk
      assessments pertaining to capital sentencing. This paper also reviews various
      methods for individualizing the application of base rates to specific cases.

PMID- 9549881
TI  - Hypnotic interviewing: the best way to interview eyewitnesses?
AB  - It has been suggested that hypnosis techniques may have the potential to enhance
      eyewitness memory in forensic investigations. However, laboratory research shows
      that increases in recall with hypnosis techniques are often associated with
      decreases in accuracy, false confidence in incorrect information, and increased
      suggestibility to leading questions and misleading post-event information. These
      problems limit the usefulness of hypnosis as an interviewing procedure. However,
      in practical investigations, many factors associated with hypnosis, apart from
      the hypnotic induction itself, might lead to memory enhancement compared with
      standard police interviews. For example, hypnotic interviewers, because of their
      psychological, clinical, and interpersonal skills, may be better interviewers
      than police officers. They may use effective interviewing strategies such as
      those associated with the "cognitive interview"; a procedure which has the
      potential to enhance recall by approximately 35% without the problems of memory
      distortion associated with hypnosis. It is concluded, therefore, that a cognitive
      interview procedure should be used in preference to hypnosis.

PMID- 9549882
TI  - Naphthoquinone esters from the root of Rhinacanthus nasutus.
AB  - Reinvestigation of the root of Rhinacanthus nasutus afforded, in addition to
      rhinacanthin-A to -D reported previously, two new
      dimethyldihydropyranonaphthoquinone esters (5, 6) and eight new 2-hydroxy-1,4
      naphthoquinone esters (7-14) were isolated. The stereochemistry of rhinacanthin-A
      was determined as the R configuration. Compounds rhinacanthin-G to -N, belong to
      a class of 2-hydroxy-3-(3-hydroxy-2,2-dimethylpropyl)-1,4-naphthoquinone esters,
      and so far have been isolated only in this plant. Their biosynthesis is also
      discussed.

PMID- 9549883
TI  - Synthesis of optically active alpha-(p-chlorophenyl)pyridylmethanols with plant
      cell cultures.

PMID- 9549884
TI  - Immunosuppressive components from an Ascomycete, Diplogelasinospora grovesii.
AB  - Two known fungal metabolites, macrophin and colletodiol, and a new stereoisomer
      of colletodiol named 10-epi-colletodiol, were isolated as immunosuppressive
      principles from an Ascomycete, Diplogelasinospora grovesii. The IC50 values of
      the major active component among them, macrophin, were calculated to be 0.4 and
      0.3 microgram/ml against concanavalin A- and lipopolysaccharide-induced
      proliferations of mouse spleen lymphocytes, respectively. A new natural product,
      4,8-dimethyl-1,5-dioxacyclooctane-2,6-dione, and a known fungal metabolite,
      isosclerone, which showed no immunosuppressive activity, were also isolated from
      this fungus.

PMID- 9549885
TI  - Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of
      gastrin/cholecystokinin-B receptors.
AB  - A novel series of phenoxyacetic acid derivatives was synthesized based on
      considerations of the three-dimensional structural similarity of YM022 and
      RP72540. The gastrin/cholecystokinin (CCK)-B and CCK-A receptor antagonist
      activities of these compounds were evaluated by investigation of their affinities
      for human gastrin/CCK-B receptors and human CCK-A receptors, respectively. It was
      found that N-methyl-N-phenyl-2-[2-[N-(N-methyl-N-phenyl-carbamoylmethyl)-N-[2 -[3
      (3- methylphenyl)ureido]acetyl]amino]phenoxy]acetamide (20k, DZ-3514) exhibited
      high affinity for gastrin/CCK-B receptors and high selectivity over CCK-A
      receptors.

PMID- 9549886
TI  - A new 5-HT3 receptor ligand. II. Structure-activity analysis of 5-HT3 receptor
      agonist action in the gut.
AB  - Several modified 2-piperazinyl benzoxazole derivatives, which exhibit an
      agonistic effect on gastrointestinal motility, were synthesized and their effects
      on the contraction of guinea-pig ileum were examined. The quaternary piperazinyl
      benzoxazole structure has a restricted conformation and stereostructure compared
      to those of the other 5-HT3 receptor agonists, serotonin and meta
      chlorophenylbiguanide. The mutual positions of the aromatic ring, nitrogen atom
      and terminal amine are considered to form the pharmacophore of the 5-HT3 receptor
      agonist in the gut. In the serotonin-evoked reflex bradycardia [Bezold-Jarisch (B
      J) reflex] inhibition test using rats the B-J reflex-inducing ratio was different
      for each synthesized compound. These results suggest that, in these 5-HT3
      receptor agonists, the substituents of the benzoxazole ring influence the B-J
      reflex-inducing activity in rats.

PMID- 9549887
TI  - Design of plasma kallikrein inhibitors: functional and structural requirements of
      plasma kallikrein inhibitors.
AB  - The synthetic plasma kallikrein (PK) inhibitor trans-4
      aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527)
      consists of three parts. Each part was replaced by analogues in an attempt to
      improve the potency and the selectivity of PKSI-527. Among the peptides examined,
      trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide
      16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being
      as potent as PKSI-527.

PMID- 9549888
TI  - Design and racemic synthesis of conformationally restricted carbocyclic
      pyrimidine nucleoside analogs based on the structure of the L-nucleoside residue
      in heterochiral DNA.
AB  - Carbocyclic pyrimidine nucleoside analogs which have restricted glycosidic
      conformation at chi approximately 180 degrees were designed, based on the
      conformational features of the L-nucleotide residue in heterochiral DNA, and
      synthesized. The synthesis of (+/-)-carbocyclic 6,6'-O-cyclo-2'-deoxyuridine was
      achieved via bromination and subsequent intramolecular cyclization of carbocyclic
      6'beta-hydroxy-2'-deoxyuridine. (+/-)-Carbocyclic 6,6'-O-cyclo-2'-deoxycytidine
      was synthesized from protected carbocyclic 6,6'-O-cyclo-2'-deoxyuridine via the 4
      triazole intermediate.

PMID- 9549889
TI  - Dissolution difference between acidic and neutral media of acetaminophen tablets
      containing a super disintegrant and a soluble excipient. II.
AB  - The disintegration and dissolution of acetaminophen tablets containing sucrose
      and Ac-Di-Sol/Primojel was significantly different between acidic and neutral
      media. The purpose of this study was to investigate the mechanism of this
      phenomenon and to propose a way of reducing the dissolution difference between
      the two media. Tablets of different combinations of active ingredient, sucrose,
      and Ac-Di-Sol/Primojel were prepared and their dissolution in various media was
      evaluated. The dissolution differences were found to be largely related to the
      hydrophobicity of the active ingredient and pH difference of the two media. This
      difference was even more evident under the condition where acetaminophen,
      sucrose, and Primojel were combined. The dissolution difference was therefore
      attributed to the depressed function of Primojel in the acidic medium, the
      stronger binding of sucrose, the hydrophobicity of the active ingredient and pH
      difference of the two media. Increasing the concentration of Primojel or
      incorporating the surfactant in the tablet can thus greatly decrease the
      dissolution difference between acidic and neutral media.

PMID- 9549890
TI  - Influence of water-soluble polymers on the dissolution of nifedipine solid
      dispersions with combined carriers.
AB  - The objective of this investigation was to clarify the influence of water-soluble
      polymers on the dissolution behavior of nifedipine from solid dispersions with
      combined carriers. All the solid dispersions of nifedipine were prepared by the
      fusion method using nicotinamide and 4 different water-soluble polymers,
      hydroxypropylmethyl-cellulose (HPMC), polyvinylpyrrolidone (PVP), partially
      hydrolyzed polyvinyl alcohol (PVA) and pullulan. HPMC, PVP or PVA dissolved in
      the fused liquid of nicotinamide and operated efficiently on the amorphous
      formation of nifedipine in solid dispersions. In dissolution studies, the drug
      concentration for these dispersions increased to more than twice intrinsic drug
      solubility. The rank order of the drug concentration was HPMC > PVP > PVA.
      However, since pullulan did not dissolve in the fused nicotinamide, nifedipine
      was present as a crystalline state in the solid dispersion; the supersaturation
      behavior of the drug was scarcely observed. The compatibility, namely, the
      solubility and miscibility, between nicotinamide or nifedipine and the polymers,
      was determined by differential scanning calorimetry using the mixtures treated
      with fusing and subsequent rapid cooling. Both HPMC and PVP exhibited high
      compatibility not only with nicotinamide but also with nifedipine. The
      crystallization behavior of nifedipine from a supersaturated solution containing
      nicotinamide or the polymers was studied. The inhibitory effect of HPMC or PVP
      for drug crystallization was evident, which would be related not to the
      solubilizing effect but to the adhesive force of the polymer for the drug.
      Therefore, it was understood that the use of a polymer with high compatibility
      and adhesion with nifedipine provides a high supersaturation level of the drug in
      dissolution. Further, the solubility parameter was found to be useful for
      selecting a suitable polymer as a component of combined carriers.

PMID- 9549891
TI  - Structural determination of unknown subsidiary colors in commercial food red Nos.
      2 and 102.
AB  - Major subsidiary colors A (Sub A) and B (Sub B) in commercial Food Red No. 102,
      and colors C (Sub C) and D (Sub D) in commercial Food Red No.2 were isolated.
      These structures were characterized by physicochemical evidence. The structures
      of Sub A, B, and C are trisodium salt of 7-hydroxy-8-(6-sulfonaphthyl-2-azo)-1,3
      naphthalenedisulfonic++ + acid, disodium salt of 4-amino-3-(4-sulfonaphthyl-1
      azo)-1-naphthalenesulfonic acid and trisodium salt of 3-hydroxy-4-(6
      sulfonaphthyl-2-azo)-2,7-naphthalenedisulfonic++ + acid, respectively. Sub D was
      identified as Sub B.

PMID- 9549893
TI  - A new oleanene glucuronide having a branched-chain sugar from Melilotus
      officinalis.
AB  - A new oleanene glucuronide called melilotus-saponin O1 (1) was isolated together
      with three known ones from the roots of Melilotus officinalis (L.) PALLAS
      (Leguminosae). The structure of 1 was determined to be 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1--> 3)]- beta-D
      galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl soyasapogenol B by
      spectroscopic and chemical methods.

PMID- 9549892
TI  - Comparative study of seventeen Salvia plants: aldose reductase inhibitory
      activity of water and MeOH extracts and liquid chromatography-mass spectrometry
      (LC-MS) analysis of water extracts.
AB  - The dry root and rhizome of Salvia miltiorhiza (Lamiaceae) are used as a crude
      drug Danshen, while those of S. deserta (Xinjiang-Danshen) are mixed in Danshen
      at Xinjiang province when the former is in short supply. The water and MeOH
      extracts of S. deserta showed strong aldose reductase (AR) inhibitory activity,
      and their active constituents were determined to be polar compounds different
      from "tanshinones" of S. miltiorhiza, i.e., lithospermic acid B (1), salvianolic
      acid K (2), salviaflaside (3), and rosmarinic acid (4) (IC50, 2.63-3.91 microM).
      We also examined the AR inhibitory activity of water and MeOH extracts of
      seventeen Salvia plants, including ten species of Danshen resources (S.
      bowleyana, S. deserta, S. miltiorhiza, S. miltiorhiza var. miltiorhiza f. alba,
      S. paramiltiorhiza, S. paramiltiorhiza f. purpureo-rubra, S. przewalskii, S.
      przewalskii var. mandarinorum, S. sinica f. purpurea, S. trijuga), and their
      water extracts were also analyzed by liquid chromatography-mass spectrometry (LC
      MS). The results indicated that there were four types with regard to the AR
      inhibitory activity and three types with regard to the amount of 1. Ten species
      used as Danshen resources showed good correlation between the AR inhibitory
      activity and the morphological classification. However, the intensities of their
      AR inhibitory activity varied, and they contained 1 in varying amounts. These
      facts suggested that the ten species were not the same, and thus their use as a
      Danshen resource should be based on their activity and/or active constituents.

PMID- 9549894
TI  - Cytotoxic principles of a Bangladeshi crude drug, akond mul (roots of Calotropis
      gigantea L.).
AB  - Three cardenolide glycosides, calotropin (1), frugoside (2), and 4'-O-beta-D
      glucopyranosylfrugoside (3), were obtained as the cytotoxic principles of "akond
      mul" (roots of Calotropis gigantea L.). The cytotoxicity of these compounds
      against various cell lines of human and mouse origin was tested. They showed
      similar cell line selectivity to those of cardiac glycosides such as digoxin and
      ouabain: they are toxic to cell lines of human origin, but not to those from
      mouse at 2 micrograms/ml.

PMID- 9549895
TI  - Application of tumbling melt granulation method to prepare controlled-release
      beads by coating with mixture of functional non-meltable and meltable materials.
AB  - A new coating method for use in preparing controlled-release beads was developed
      by modifying the tumbling melt granulation technique. The dissolution rate of the
      drug from the beads was controlled by coating the mixture of meltable and non
      meltable materials by heating in a centrifugal fluidizing granulator without
      using any solvent. In experiments using talc as the non-meltable material, the
      resultant beads showed the sufficient ability to suppress the dissolution of the
      drug and no change in the dissolution characteristics by wetting agent and in a
      stability test at high temperature. Using functional polymer as the non-meltable
      material, the controlled-release beads with various dissolution characteristics
      could be prepared: entero-soluble-release beads using entero-soluble polymer, and
      zero-order-release beads using hydrophilic gel-forming agent and talc.

PMID- 9549896
TI  - Application of tumbling melt granulation (TMG) method to prepare controlled
      release fine granules.
AB  - The tumbling melt granulation (TMG) method was applied to prepare controlled
      release fine granules of diltiazem hydrochloride (DH). The entire process, from
      the preparation of the cores by the adherence of DH to the sucrose crystal to the
      subsequent coating of the controlled-release layer, was performed without using
      any solvent. A mixture of meltable material, talc, and ethylcellulose was used
      for the controlled-release layer and controlled-release fine granules
      approximately 400 microns in diameter were obtained with excellent producibility.
      The dissolution rate of DH from these fine granules was similar to that of a once
      a-day dosage form obtained in the market; further, the dependency of the
      dissolution profile on pH of the media was less. Thus, it was concluded that this
      TMG method was very useful for preparing not only controlled-release beads of
      granule size (usually 500 to 1400 microns) but also fine granules.

PMID- 9549897
TI  - Reduction of Mn(3+)-tetrakis(4-methylpyridyl)porphine with albumin observed in
      resonance Raman spectra.
AB  - When the resonance Raman spectra of Mn(3+)-tetrakis(4-methylpyridyl)-porphine are
      measured in the presence of albumins, the resonance Raman bands of Mn(2+)
      tetrakis(4-methylpyridyl)porphine are frequently observed. This reduction of Mn3+
      to Mn2+ could be caused by an action of unfolding albumins resulting from heat
      and/or light.

PMID- 9549899
TI  - Lethal monointoxication by overdosage of MDEA.
AB  - A 19-year-old man died after the intake of ten tablets of Ecstasy containing 3,4
      methyl-enedioxy-N-ethylamphetamine (MDEA) as the main active ingredient.
      According to an eyewitness the symptoms of intoxication were strong sweating,
      sudden aggressiveness followed by hallucinations, subsequent failure of motoric
      coordination, severe spasms of arms and back, complete depression of the
      respiratory system, unconsciousness, and collapse. Resuscitation by an emergency
      doctor failed. Major autopsy findings were severe vascular congestion of all
      internal organs, liquid post-mortem blood, numerous subpleural and subepicardial
      petechial haemorrhages. By GC/MS analysis, MDEA was found in large amounts in
      serum (12 mg/l in femoral vein, 22 mg/l in heart blood serum), urine (201 mg/l),
      brain (18 to 28 mg/l) and in other tissue samples. Scalp-hair was highly positive
      for MDEA (17 ng/mg). Besides MDEA and its metabolites only trace amounts of MDMA
      could be found in urine and blood; no other drugs were detected. It can be
      concluded that the cause of death was a monointoxication by overdosage of MDEA.

PMID- 9549898
TI  - The different mobility of complementary strands depends on the proportion AC/GT.
AB  - The electrophoretic mobility of DNA fragments on denaturing polyacrylamide gel
      depends on various factors. One of these is the base composition of a single
      stranded DNA (ssDNA). We confirmed that one strand and its complementary strand
      of polymerase chain reaction (PCR) products migrated with different mobilities in
      all alleles detected at 12 out of the 13 short tandem repeat (STR) loci studied.
      The mobility differences between complementary strands (MD) were also observed
      regardless of end-polishing with Pfu DNA polymerase. MD was therefore not
      influenced by additional nucleotides to each strand of the PCR products. We then
      analyzed the relation between MD and the base composition using one
      representative allele at each of the 13 loci. The results indicated that MD was
      affected by the adenine plus cytosine (AC) content in the ssDNA and was
      proportional to the values of the AC content divided by the guanine plus thymine
      (GT) content in the AC-rich strand (the proportion AC/GT). When the proportion
      AC/GT was well-balanced, MD decreased. The same tendency was observed even in the
      end-polished strands. In this study, the electrophoretic mobility of an ssDNA on
      denaturing polyacrylamide gels was shown to depend on the proportion AC/GT.
      Unless the same side of the PCR products is labelled in the context of a PCR
      based STR typing, distinct alleles may be mistaken for identical ones because of
      the different mobility of complementary strands. Accordingly, the labelled strand
      should be described if only one strand of the PCR products is detected. When
      using an allelic ladder marker as a size standard, the labelled side should be
      unified between STR alleles and the allelic ladder alleles.

PMID- 9549900
TI  - German population data of three tetrameric short tandem repeat loci--D3S1744,
      D12S1090 and D18S849.
AB  - Allele and genotype frequencies of the three tetrameric short tandem repeat (STR)
      1 Oci D351744 D1251090 and D185849 were analyzed in a German sample population
      using a multiplex PCR and electrophoresis of amplified products in denaturing
      gels followed by silver staining. Testing for Hardy-Weinberg equilibrium showed
      no significant deviation at the three loci.

PMID- 9549901
TI  - Exploitation of autopsy in determining natural cause of death: trends in Finland
      with special reference to the diagnostics of ischemic heart diseases and
      cerebrovascular diseases in middle-aged males, 1974-1993.
AB  - Finnish mortality statistics show a marked decrease in coronary disease mortality
      especially among middle-aged males during the last 20 to 25 years. At the same
      time, the overall autopsy rate in deaths due to natural, non-violent causes has
      diminished in Finland. National mortality statistics are based on medical
      information given in death certificates. How often are the causes of death based
      on autopsy and is there any definitive trend? Possible changes in cause-of-death
      determination practices may have contributed to the mortality changes observed.
      In this study, deaths due to ischemic heart diseases (IHD) and cerebrovascular
      diseases (CVD) from 1974 to 1993 in Finland were compared with natural deaths,
      i.e. all of the deaths due to natural causes, in regard to use of autopsy. It was
      found that IHD-diagnosis as the underlying cause-of-death was, unlike natural
      deaths and CVD in particular, increasingly based on autopsy. It is thus concluded
      that the recent decline in coronary disease mortality among middle-aged men in
      Finland cannot be explained by any deterioration in cause-of-death examination
      practices.

PMID- 9549902
TI  - Study of the diagnostic value of strontium, chloride, haemoglobin and diatoms in
      immersion cases.
AB  - Tests of haemoglobin (Hb), strontium (Sr) and chloride (Cl), as well as diatoms,
      toxicological and pathological studies were performed in biological samples from
      133 immersion fatalities occurred since 1991 to 1996 in central and northern
      Spain. Hb, Sr, and Cl where analyzed in blood samples where increasing
      decomposition could be demonstrated in most of the cases. The samples were
      frequently accompanied with well documented forensic reports, including autopsies
      findings and other circumstances of the death. The goal of our study is to
      evaluate the difference of blood Sr concentration between the left and right side
      of the heart (LVSr-RVSr) as a marker of drowning. For this purpose, the cases
      investigated were classified in 'typical drowning' (TD) cases and 'atypical
      drowning' (AD) cases. This last group was used as a control. The comparison of
      the LVSr-RVSr between TD and AD cases was highly significant (P = 0.0002) in
      blood specimens extracted from cases occurred in putative drowning media where Sr
      concentration was higher than 800 micrograms/l. No significant differences were
      found comparing neither Cl nor Hb biventricular concentrations between TD and AD
      cases in blood samples extracted from bodies found in both fresh and seawater.

PMID- 9549903
TI  - Phrenic nerves and diaphragms in sudden infant death syndrome.
AB  - Disturbances of the respiratory system may be an important factor in the cascade
      of events leading to sudden infant death syndrome (SIDS). Even though the
      diaphragm is the major respiratory muscle in infants, little is known about
      alterations of this muscle and of the phrenic nerve in SIDS. In the present
      study, diaphragms and phrenic nerves of 24 SIDS infants and seven controls were
      analyzed. Morphometric analysis revealed only slightly larger cross sectional
      areas of phrenic nerve axons but no increase in myelin sheath thickness in SIDS
      cases. However, in one SIDS case, myelinated nerve fibre density was severely
      reduced. Using electron microscopy, several nerve fibres of SIDS infants showed
      focal accumulations of neurofilaments. Muscle fibre diameters in SIDS diaphragms
      were significantly larger compared to controls (P < 0.0001). However, in almost
      all SIDS and control cases, axons and myelin sheaths were artificially swollen,
      and acute segmental muscle fibre ruptures and contracture bands were found. These
      prominent nonspecific ultrastructural alterations should advise caution in the
      interpretation of morphometric data. Thus, in some cases exemplified by one case
      of the present series, decreased density of phrenic nerve myelinated axons might
      contribute to SIDS. Still, the present results indicate that development of
      phrenic nerves and diaphragms is not delayed in most SIDS infants.

PMID- 9549904
TI  - A contribution to a possible differentiation between SIDS and asphyxiation.
AB  - The singular and combined appearance of conjunctival petechiae, of acute
      pulmonary emphysema and of signs of aspiration was evaluated in resuscitated and
      non-resuscitated children dying of SIDS (n = 115), of other causes of natural
      death (n = 17), of severe head injury (n = 10) and of asphyxiation/strangulation
      (n = 7). Conjunctival petechiae occurred in all of the asphyxiated victims and in
      five out of 10 children dying of severe head injury, but were exclusively found
      in four resuscitated babies and one baby with questionable resuscitation trials
      of the SIDS-group (4%), furthermore in one resuscitated child dying of a
      congenital heart defect. Acute pulmonary emphysema was detected in six out of the
      seven children of the asphyxiation/strangulation group, in two resuscitated
      children with head injury and in five resuscitated babies dying of SIDS. Both
      parameters were observed exclusively in the asphyxiation/strangulation group (71%
      of the cases) but not in the control cases. Therefore, it can be concluded that
      the simultaneous appearance of conjunctival petechiae and of acute pulmonary
      emphysema strongly indicates death by asphyxiation.

PMID- 9549905
TI  - Statistical analysis of sexual offenders--a preliminary study.
AB  - It is suggested that persons arrested and incarcerated for sexual offences are in
      some ways different than other inmates. This paper examines various
      characteristics of sexual offenders in an Irish prison and determines if
      perceived differences are statistically valid using some of the techniques
      available through offender profiling. Statistical differences (chi 2; P = 0.01)
      in some characteristics were found between other prisoners and sexual offenders.

PMID- 9549906
TI  - Fluid transport in vascularized tumours and metastasis.
AB  - In this paper we propose a modification to a model of R. K. Jain and L. T. Baxter
      used to describe fluid transport in vascularized tumours. The model predicts high
      interstitial pressure in the interior of the tumour together with a rapid
      decrease in pressure to its periphery in agreement with experiment and the
      predictions of the Jain-Baxter model. By the addition of a pressure-curvature
      (Gibbs-Thomson) condition on the periphery of the tumour we are able to show by a
      perturbation analysis that a lowering of the interstitial pressure can retard
      tumour growth. Lowering interstitial pressure may also be beneficial to the
      targeting of therapeutic drugs.

PMID- 9549907
TI  - The competent graduate.

PMID- 9549908
TI  - Specialisation in oral surgery.

PMID- 9549909
TI  - Advances in periodontal diagnosis. 4. Potential microbiological markers.
AB  - The potential of bacterial markers for the detection of periodontal disease
      activity is discussed. Chronic periodontitis has been associated with subgingival
      bacteria. Techniques are available to detect and distinguish different bacteria.
      In subgingival plaque, bacterial proteases can be detected. Commercial diagnostic
      tests based on bacterial factors are described.

PMID- 9549910
TI  - Powered toothbrushes.
AB  - Powered toothbrushes were first developed over 50 years ago. More recent advances
      in design and technology mean that there are now a considerable number of
      different models available on the market. It is not surprising, therefore, that
      patients, when considering buying a powered toothbrush, often turn to their
      general dental practitioner for advice.

PMID- 9549911
TI  - A psychodynamic theory for dental phobia.
AB  - Dentists recognise various degrees of dental anxiety in their patients. There are
      those who are relaxed, those who are anxious and those who are dentally phobic.
      The question remains why should disagreeable dental experiences result in dental
      anxiety in one patient, have little effect upon another and cause dental phobia
      in a third? The aim of this paper is to propose a psychodynamic theory for dental
      phobia based upon the ideas of false connections and displacement.

PMID- 9549912
TI  - Enthusiastic welcome for the pilot peer review scheme for GDPs working in the
      GDS.

PMID- 9549913
TI  - Most referrals for periradicular surgery do not match the accepted guidelines.

PMID- 9549914
TI  - An accurate method for the measurement of blood loss during dental procedures.

PMID- 9549915
TI  - A report of an evaluation of the pilot peer review scheme for general dental
      practitioners working in the general dental services in England.
AB  - OBJECTIVE: To evaluate the pilot peer review scheme for general dental
      practitioners, working in the general dental services in England. DESIGN: A
      retrospective analysis of a 50% random sample of end of project resumes. SETTING:
      The scheme was piloted from August 1991 to April 1996. At the end of each project
      a resume was completed. METHODS: The random sample of resumes was subjected to
      content analysis by three reviewers who had previously undergone consistency
      training. MAIN OUTCOME MEASURES: The range of topics reviewed, the choice of
      single or multiple topics, the direct relevance of projects to patient care and
      the comments of the scheme's participants. RESULTS: 332 resumes were analysed,
      89% included positive comments. Overall 42% of projects reviewed single topics,
      with participants in 4 out of 13 regions favouring this approach. 61% of topics
      related directly to patient care. CONCLUSIONS: The pilot peer review scheme was
      enthusiastically welcomed by the participants and achieved its objectives of
      encouraging initiatives to improve patient services and testing different types
      of peer review.

PMID- 9549916
TI  - A study of suitability of referrals for periradicular surgery.
AB  - OBJECTIVE: To determine if the clinical and radiographic presentation of patients
      referred by their general dental practitioner requesting periradicular surgery
      fulfilled a set of predetermined guidelines as to the appropriateness of the
      procedure. DESIGN: Multicentre prospective study. SETTING: Maxillofacial
      departments of district general hospitals. METHOD: Consecutive analysis of
      referrals within four hospitals over a 1-year period between 1995 and 1996.
      RESULTS: From 205 referrals, mostly of patients in the 30 to 40 years age group,
      79.5% (n = 163) of referrals failed to meet the criteria, mainly because of an
      unsatisfactory root canal filling, but also due to obvious coronal microleakage
      and adjacent teeth contributing to the disease process not yet having received
      endodontic treatment. In only 6.3% (n = 13) of patients had there been an attempt
      to retreat the pulp space infection by conventional means. CONCLUSION: The
      majority of referrals in this study did not fulfil the guideline criteria on the
      provision of periradicular surgery. The factors influencing failure in
      endodontics and periradicular disease did not appear to have been appreciated, or
      were not acted upon. Conventional retreatment of the pulp space needs to be
      considered or attempted prior to referral for surgery.

PMID- 9549917
TI  - A randomised trial of calcium alginate swabs to control blood loss in 3-5-year
      old children.
AB  - OBJECTIVE: To compare the effectiveness of calcium alginate swabs and traditional
      cotton swabs in the control of blood loss after extraction of deciduous teeth
      from healthy children, aged 3-5 years, under general anaesthetic. DESIGN:
      Prospective, randomised clinical trial. SETTING: General anaesthetic suite in a
      dental teaching hospital. SUBJECTS: 101 patients were recruited to the study,
      comprising 50 randomised to be treated with cotton swabs and 51 with alginate
      swabs. INTERVENTIONS: Teeth were extracted under general anaesthesia and blood
      collected for measurement in order to compare blood loss using the two systems.
      MAIN OUTCOME MEASURES: The number of teeth extracted ranged from 1-14. The total
      blood loss ranged from 0.53-78.13 ml with a median of 12.9 ml. CONCLUSION:
      Calcium alginate swabs were not found to produce any clinical or statistical
      advantage over traditional cotton swabs in this surgical setting.

PMID- 9549918
TI  - An innovation in the assessment of future dentists.
AB  - 'The assessment of students is a serious and often tragic enterprise.' The
      central question in assessment is 'What is one trying to assess?'. Is it factual
      knowledge, ability to apply and problem solve, clinical competencies or indeed
      other attributes? The domain being assessed requires appropriate methods.
      Professionals involved in examination development have identified three
      characteristics which all assessment methods demand: reliability, validity and
      feasibility. This article sets out to describe these features.

PMID- 9549919
TI  - Pathogenesis of polycythemia vera: do we have the right pieces to the puzzle?

PMID- 9549920
TI  - Expression of adhesion molecules in chronic B-cell lymphoproliferative disorders.
AB  - BACKGROUND AND OBJECTIVE: Abnormalities in the expression of cell adhesion
      molecules (CAM) are thought to influence the patterns of intranodal growth and
      hematogeneous spread of malignant cells in chronic lymphoproliferative disorders
      (LPD). Therefore, the characterization of CAM phenotypic profiles of the
      neoplastic clones in LPD may help to identify distinct subtypes with prognostic
      implications. In this work we sought to investigate whether the expression of CAM
      by circulating malignant cells in patients with B-cell LPD differed from that of
      normal peripheral blood B-lymphocytes (PBL) and whether the observed phenotypic
      patterns could be correlated to other biological and clinical parameters of known
      clinical relevance. DESIGN AND METHODS: Peripheral blood mononuclear cells were
      obtained from 148 patients with B-cell chronic lymphocytic leukemia (B-CLL), 52
      with B-cell non-Hodgkin lymphomas (NHL) and 10 with hairy cell leukemia (HCL).
      The expression of CAM was analyzed by flow cytometry using monoclonal antibodies
      against CD49d, CD29, CD11a, CD11b, CD11c, CD18, CD62L, CD54 and CD44. RESULTS:
      All CAM were detected in normal peripheral blood B-lymphocytes, except CD11c and
      CD54, which were present in only a minority of cells. Fluorescence mean channel
      values (FMC) showed that all molecules, with the exception of CD44, were
      expressed with dim intensity. Emerging patterns of CAM expression, as assessed by
      FMC values, were observed in different LPD: thus, B-CLL is characterized by a
      very low expression of CD49d/CD29 and beta 2 integrins. In this disorder,
      CD49d/CD29, CD11a, and CD54 increase with tumor burden; NHL show high expression
      of CD29 and CD54; strong expression of all molecules (except CD11a) was found in
      HCL, particularly CD11c (FMC values 60 times higher than normal). CD62L was
      faintly expressed in all diagnostic groups, whereas CD11c showed consistently
      high FMC values. INTERPRETATION AND CONCLUSIONS: The data shows that the
      phenotypic characterization of LPD can be further refined by the analysis of
      their patterns of CAM expression which may help to identify distinct subsets
      within each nosological group.

PMID- 9549921
TI  - Cytoskeletal reorganization after preparation of platelet concentrates, using the
      buffy coat method, and during their storage.
AB  - BACKGROUND AND OBJECTIVE: The use of platelet transfusions has risen considerably
      in the last years. Changes occur in platelet biochemical and membrane properties
      during storage. We have analyzed the effect of platelet preparation and storage
      of platelet function through the evaluation of platelet cytoskeletal
      reorganization. METHODS: A blood sample was obtained from the donor and platelets
      were separated as standard platelet-rich plasma (PRP) (120 g, 20 min) (PRE
      sample). Aliquots were also collected immediately after preparation using buffy
      coat procedure of platelet concentrates (day 0) and after 1, 3 and 5 days of
      storage. Cytoskeleton composition in both low- and high-speed cytoskeletal
      fractions of detergent-lysed platelets was analyzed by gradient SDS
      polyacrylamide gel electrophoresis (SDS-PAGE). Presence of each contractile
      protein was quantified by densitometry. RESULTS: The method used to prepare
      platelet concentrates induced actin polymerization (actin increased to 163.5 +/-
      4.8%, mean +/- SEM, n = 8, p < 0.001, considering actin values in PRE sample as
      100%) with a concurrent increase in the association of actin-binding protein
      (ABP), myosin and alpha-actinin to the low-speed cytoskeletal fraction. During
      the first 24 hours of storage, cytoskeletal assembly was partially reversed
      (134.8 +/- 2.6% of actin, p < 0.001) and actin polymerization increased gradually
      to 144.3 +/- 5.8% and 153.2 +/- 5.1% at days 3 and 5, respectively (p < 0.001 for
      both days). ABP, myosin and alpha-actinin showed similar tendencies to those
      referred for actin. Conversely, during platelet preparation and storage, the
      contractile proteins associated with the high-speed cytoskeletal fraction
      decreased, due to reorganization of the contractile proteins to the low speed
      fraction. INTERPRETATION AND CONCLUSIONS: The method used to prepare platelet
      concentrates (buffy coat procedure) induced cytoskeletal polymerization. This
      activating effect was partially reversed after 1 day of storage, although it
      increased progressively after 3 days of storage. The storage lesion may lead to
      defective cytoskeletal assembly in response to further stimulus. Analysis of
      cytoskeletal assembly is a sensitive method for detecting platelet activation
      caused by the concentrate preparation method and the storage conditions.

PMID- 9549923
TI  - Therapeutic options and treatment results for patients over 75 years of age with
      acute myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVE: Acute myeloid leukemia (AML) is a prevalent disease of
      the elderly. Given the progressive aging of the general population, the frequency
      of the disease will further increase, especially in very old individuals. In a
      cohort of 70 consecutive AML patients aged over 75 years, we investigated the
      clinico-hematological characteristics and treatment results. DESIGN AND METHODS:
      Seventy patients aged > 75 were diagnosed at our institutions as having AML
      between January 1987 and December 1996. This figure represents 8% of the whole
      AML patient population observed during the same period. These patients were
      studied concerning the main clinical and hematological features at presentation,
      therapeutic approach and clinical outcome. RESULTS: A myelodysplastic syndrome
      preceded the onset of AML in 10 patients (14%). Trilinear myelodysplasia was
      present in 28 patients (40%). Hypocellular leukemia was diagnosed in 12 cases
      (17%). An active infection was found in 12 patients (17%). Aggressive
      chemotherapy was given to 22 patients (31%), low-dose ARA-C (LDARA-C) to 7
      patients (10%), while 41 (58%) were managed with supportive care and/or
      hydroxyurea (HU). Therapeutic choice was significantly influenced by performance
      status (p = .03), infections (p = .0001), severe co-morbid disease (p = .0001),
      and hypocellular AML diagnosis (p = .0001). Complete remission (CR) was obtained
      in 7/22 patients aggressively treated (32%), 0/7 in the LD-ARA-C group, and in
      one patient treated with HU. The median survival for the whole patient population
      was 18 weeks. There was no significant difference among the three treatment
      groups. However, patients achieving CR experienced significantly longer survival
      as did those with hypocellular leukemia. INTERPRETATION AND CONCLUSIONS: In spite
      of a relevant selection at diagnosis, intensive chemotherapy is not appropriate
      for the majority of very old patients with AML. However, since a minority of
      patients takes substantial advantage from an aggressive approach, any effort
      should be made to preliminarily identify this subset at diagnosis.

PMID- 9549922
TI  - The effect of dietary magnesium supplementation on the cellular abnormalities of
      erythrocytes in patients with beta thalassemia intermedia.
AB  - BACKGROUND AND OBJECTIVE: Reduced serum or erythrocyte Mg have been reported in
      human beta thalassemia. These deficiencies may play a role in the cellular
      abnormalities characteristic of this disorder. We have therefore studied the
      effect of dietary Mg supplementation in patients with beta thalassemia intermedia
      in order to establish whether it improves the abnormalities of thalassemic
      erythrocytes. DESIGN AND METHODS: Plasma and erythrocyte Mg were determined in 11
      patients with b thalassemia intermedia, not requiring chronic transfusion
      therapy, and in 17 normal controls. Inclusion criteria included normal renal and
      liver function and performance status of 70% or greater. Seven patients were
      enrolled for the Mg supplementation study, after the appropriate informed consent
      was obtained. They were given a starting dose of 0.6 mEq/kg/day of magnesium
      pidolate, divided into two oral daily doses, for four weeks. In a 70-kg subject,
      a daily Mg dose of 42 mEq corresponds to 504 mg of Mg, with the daily Mg intake
      of normal subjects being 418 +/- 120 mg for males and 343 +/- 94 mg for females.
      After 28 days of treatment, five of the patients continued the protocol with a
      daily dosage increased to 1.2 mEq magnesium pidolate/kg/day, divided into two
      oral administrations, for an additional four weeks. RESULTS: In patients with
      untransfused beta thalassemia intermedia we found reduced erythrocyte Mg (in
      mmol/kg Hb, 6.12 +/- 1.5, n = 11 vs. 8.69 +/- 0.89, n = 17, respectively, p <
      0.0001) and normal serum Mg. In the seven patients given oral Mg supplements, at
      Mg dosages of 0.6 mEq/kg/day we observed significant increases in erythrocyte Mg,
      and significant improvement in some of the characteristic abnormalities of beta
      that erythrocytes (increased Na-K pump, KCl cotransport, cell dehydration,
      increased osmotic resistance). These changes were maintained in the 5 patients
      who were treated with 1.2 mEq of Mg/kg/day. Follow-up studies showed a return to
      baseline conditions. There were no signs of Mg toxicity, with the only side
      effect being diarrhea, which was generally mild, but led to discontinuation for
      one patient after the first four weeks. INTERPRETATION AND CONCLUSIONS: These
      data indicate that dietary Mg supplementation improves some of the characteristic
      cellular function abnormalities of b thalassemia intermedia. The possible
      therapeutic value of this strategy should be further tested in these patients.

PMID- 9549925
TI  - Assessment of hematological and immunological function during long-term follow-up
      after peripheral blood stem cell transplantation.
AB  - BACKGROUND AND OBJECTIVE: Long-term hemopoietic and immunological profile after
      autologous peripheral blood progenitor cells transplantation (PBPCT), in patients
      affected by hematological malignancies is largely unknown. The aim of this work
      was to detect the impact of high dose chemotherapy and PBPCT on hemopoietic and
      immunological function compared to conventional chemotherapy. DESIGN AND METHODS:
      Patients had to fulfill the following criteria: continuous complete remission
      after PBPCT, follow-up longer than 12 months, no chemo or radiotherapy or
      biological response modifiers after PBPCT. Twenty-five patients were considered
      eligible for this analysis. Stable and complete hemopoietic reconstitution (Hb >
      12 g/dL, WB > 4.0 x 10(9)/L, ANC > 1.5 x 10(9)/L and Pits count > 150 x 10(9)/L),
      morphological examination of peripheral blood and bone marrow, cytogenetic
      analysis and immunological profile were evaluated at 12 months and yearly
      thereafter. RESULTS: Immunological reconstitution showed a persistent reduction
      of CD4/CD8 ratio up to five years after PBPCT. This reduction was related to a
      persistent increase of CD8+ lymphocytes and a constant reduction of CD4+
      lymphocytes. INTERPRETATION AND CONCLUSIONS: Defects observed in PBPCT patients
      are induced by the procedure itself, by the conditioning regimen or both. The
      different behavior in the immune reconstitution of CD8+ subset after PBPCT may be
      favored by an extrathymic origin of these cells while CD4+ subset recovery which
      is thymus-dependent is impaired after PBPCT in adult population. Long-term
      hemopoietic reconstitution after PBPCT is rapidly obtained and is stable over the
      years, long-term immunological function seems to be abnormal in these patients
      and these abnormalities are long-lasting.

PMID- 9549924
TI  - A randomized trial of high dose polyvalent intravenous immunoglobulin (HDIgG) vs.
      Cytomegalovirus (CMV) hyperimmune IgG in allogeneic hemopoietic stem cell
      transplants (HSCT).
AB  - BACKGROUND AND OBJECTIVE: The role of high dose intravenous IgG (HDIgG) and of
      hyperimmune CMV IgG (CMV-IgG) in patients undergoing allogeneic hemopoietic stem
      cell transplantation (HSCT) is still unclear. The aim of this study was to
      compare prophylactic CMV-IgG with HDIgGin a randomized prospective trial in
      allogeneic HSCT recipients: primary end point of the study was the occurrence of
      post-transplant CMV antigenemia (CMVAg-emia). Secondary end-points were severity
      of acute and chronic graft-versus-host disease (GvHD), infections and transplant
      related mortality (TRM). DESIGN AND METHODS: Patients were randomized to receive
      100 mg/kg/week of CMV-IgG (group A; n = 64) or 400 mg/kg/week of HDIgG (group B;
      n = 64) from day -7 to day +100. The two groups were comparable for age,
      diagnosis, disease status, and acute graft-versus host (aGvHD) prophylaxis.
      RESULTS: The actuarial risk at 1 year of CMV antigenemia was lower for CMV-IgG
      (61% vs. 71%) but not significantly (p = 0.37); CMVAg-emia occurred at the same
      interval from HSCT (47 vs. 48 days, p = 0.9), with a comparable number of CMVAg
      positive cells (3 vs. 3 p = 0.9). Eight patients died of interstitial pneumonia
      (IP) (4 in each group), two in group A of CMV-IP. Acute GvHD was scored as O-I,
      II and III-IV in 39 vs. 35, 23 vs. 22 and 2 vs. 7 patients respectively for the
      two groups (p = not significant). The actuarial risk of developing acute GvHD
      grade II-IV was lower for CMV-IgG (39% vs. 45%) but not significantly (p = 0.43).
      Chronic GvHD scored as absent in 7 vs. 10 patients, limited in 39 vs. 37 and
      extensive in 19 vs. 17 patients respectively (p = not significant). Numbered days
      with intravenous antibiotics, days in hospital, days of fever, number of local
      and disseminated infections, number of patients with fever of unknown origin were
      not significantly different. Actuarial 1 year TRM is 18% vs. 19%, respectively (p
      = 0.9). INTERPRETATION AND CONCLUSIONS: This study confirms that CMV antigenemia
      is comparable in recipients of hyperimmune CMV-IgG and of polyvalent HDIgG,
      although the former had a 32% lower cost. It also shows that the potential
      immunomodulating effect on acute GvHD and transplant mortality is similar with
      100 or 400 mg of IgG/kg/week: this is relevant, in view of the high cost of
      prophylactic HDIgG.

PMID- 9549926
TI  - Treatment of polycythemia vera.
AB  - BACKGROUND AND OBJECTIVE: Current guidelines for the management of patients with
      polycythemia vera (PV) derive from a few clinical trials and several uncontrolled
      clinical studies. The purpose of this paper is to critically review the available
      evidence in literature for selecting the best treatment in the single patient.
      METHODS: The authors have been working in this field contributing original papers
      whose data have been used for this study. In addition, the material analyzed in
      this article includes papers published in the journals covered by the Science
      Citation index and Medline. RESULTS: Therapeutic strategies for patients with PV
      include both cytoreductive and antithrombotic drugs. Among cytoreductive
      treatments, phlebotomy is associated with poor compliance and an increased
      incidence of thrombosis in the first three-five years, whereas chemotherapy may
      induce an higher risk of secondary malignancies after seven-ten years of follow
      up. New cytoreductive drugs virtually devoid of mutagenic risk include alpha
      interferon and anagrelide, but their role in reducing thrombotic complications or
      mortality remains to be demonstrated. Antithrombotic drugs, such as aspirin, are
      frequently used in PV, despite doubts regarding safety and efficacy. CONCLUSIONS:
      The management of patients with PV is a difficult balance between the prevention
      of thrombotic complications and the risk of drug side effects and toxicity.
      Appropriate studies are needed and an European collaboration has been set up for
      launching a randomized, placebo-controlled clinical trial (European Collaboration
      on Low-Dose Aspirin-ECLAP study) aimed at testing the efficacy of low-dose
      aspirin in preventing thrombosis and prolonging survival in PV patients.

PMID- 9549928
TI  - Clinical use of allogeneic hematopoietic stem cells from sources other than bone
      marrow.
AB  - BACKGROUND AND OBJECTIVE: Peripheral blood stem cells (PBSC) are being
      increasingly used as an alternative to conventional allogeneic bone marrow (BM)
      transplantation. This has prompted the Working Group on CD34-Positive
      Hematopoietic Cells to evaluate the current utilization of allogeneic PBSC in
      clinical hematology. EVIDENCE AND INFORMATION SOURCES: The method employed for
      preparing this review was that of informal consensus development. Members of the
      Working Group met three times, and the participants at these meetings examined a
      list of problems previously prepared by the chairman. They discussed the single
      points in order to reach an agreement on different opinions and eventually
      approved the final manuscript. Some of the authors of the present review have
      been working in the field of stem cell transplantation and have contributed
      original papers in peer-reviewed journals. In addition, the material examined in
      the present review includes articles and abstracts published in journals covered
      by the Science Citation Index and Medline. STATE OF THE ART: Review of the
      current literature shows that unmanipulated allogeneic PBSC give prompt and
      stable engraftment in HLA-identical sibling recipients. Despite the much higher
      number of T-cells infused, the incidence and severity of acute GVHD after PBSC
      transplant seems comparable to that observed with bone marrow (BM) cells. In
      comparison to the latter, PBSC probably ensure faster immunologic reconstitution
      in the early post-transplant period. Controversial results on the incidence and
      severity of acute-GVHD have been reported when CD34+ selection methods are used.
      Prospective randomized trials are underway to compare the results of PBSC and BM
      allogeneic transplantation. In mismatched family donor transplants, T-cell
      depleted PBSC successfully engraft immune-myeloablated recipients through a
      megacell-dose effect able to overcome the HLA barrier. Experience with PBSC in
      the context of unrelated donor transplants is currently anecdotal and prospective
      trials should be completed before that practice becomes routine. Finally, there
      is also limited evidence that, following induction chemotherapy, the addition of
      PBSC to donor lymphocyte infusion (DLI) for treatment of leukemia relapse after
      BMT may improve the safety and effectiveness of DLI itself. Concerning cord blood
      (CB) transplants, the most interesting aspects are the ease of CB collection and
      storage, the low risk of viral contamination and the low immune reactivity of CB
      cells. This last property has its clinical counterpart in an apparently reduced
      incidence and severity of acute GVHD both in sibling and unrelated CB
      transplants, probably making the level of donor/recipient HLA disparity
      acceptable a greater degree with respect to what is required for transplants from
      other sources.

PMID- 9549927
TI  - Pathogenesis of polycythemia vera.
AB  - BACKGROUND AND OBJECTIVE: Polycythemia vera (PV) is an acquired clonal
      myeloproliferative disorder characterized by increased production of mature red
      cells. We still lack a molecular target responsible for this disorder; however,
      recent investigations have focused on a number of molecules involved in signal
      transduction pathways mediated by erythropoietin (Epo) and other growth factors.
      Here we review the implication of these molecules in the pathogenesis of PV.
      INFORMATION SOURCES: The material reviewed in this work includes articles
      published in journals covered by Medline. We also include data obtained in our
      laboratory regarding to the significance of apoptosis inhibitory proteins in
      erythroid development. STATE OF THE ART AND PERSPECTIVES: Overproduction of
      erythroid cells in PV is particular in that it occurs in the absence of a
      recognizable physiologic stimulus, since circulating serum levels of Epo are
      normal or lower than normal. Genetic analysis as well as in vitro studies, have
      established an essential role for Epo in the survival and maturation of committed
      erythroid progenitors. Epo initiates its cellular response by binding to the Epo
      receptor (EpoR) expressed on the surface of immature erythroblasts. Following
      ligand binding, EpoR is known to activate a cytoplasmic protein tyrosine kinase,
      Jak2 which triggers a signal transduction cascade that leads to the development
      of early erythroid progenitors into mature erythroblast cells. Although the
      mechanism underlying the increased erythroid production in PV is not well
      understood, a number of causes have recently came for which may provide insights
      not only for the pathogenesis of PV but also for a fundamental biological
      process: the mechanism whereby a multipotential stem cell gives rise to a
      particular cell lineage.

PMID- 9549929
TI  - Erythrocytosis in a patient with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) can be accompanied by compensatory
      secondary erythrocytosis. However, the exact prevalence of secondary
      erythrocytosis in COPD is unknown. Although diagnostic criteria for polycythemia
      vera versus secondary erythrocytosis are mutually exclusive, we describe here the
      coexistence of polycythemia vera and COPD in the same patient.

PMID- 9549930
TI  - Blast crisis of Ph1-CML, with the prevalent features of malignant histiocytosis.

PMID- 9549931
TI  - Detection of megakaryocyte colonies in plasma clot cultures by immunoenzymatic
      staining.
AB  - In vitro induced megakaryocytic differentiation/maturation of megakayocyte (meg)
      progenitors represents an important tool for investigating cytokine-induced in
      vitro thrombocytopoiesis. We have developed an assay which allows the in situ
      study of human meg progenitor-derived colonies, cultured on a plasma clot in the
      presence of cytokines. Plates were immunostained by using an anti-alpha IIb beta
      3 monoclonal antibody and an alkaline phosphatase-labeled secondary antibody.
      alpha IIb beta 3-bearing cells were stained an intense red and were clearly
      differentiated from the negative cells. Processed plates were stable for some
      weeks at 4 degrees C. The described procedure is easy to perform and allowed us
      to enumerate the meg colonies and assess colony morphology and cell ploidy.

PMID- 9549932
TI  - Aggressive natural killer cell leukemia: report of a case in a Caucasian boy.
AB  - We report a case of aggressive natural killer cell leukemia (ANKL) in a Caucasian
      boy diagnosed on clinical, cytologic, immunophenotypic and genotypic grounds. An
      anomalous karyotype and integration of Epstein-Barr virus (EBV) within the
      leukemic population were identified.

PMID- 9549933
TI  - Allison Kitson is thought-provoking.

PMID- 9549934
TI  - What science is.

PMID- 9549935
TI  - Youngsters caring for adults with cancer.
AB  - PURPOSE: To describe the caregiving provided by children and adolescents for
      adults with cancer. Because nurses are assuming an increasingly prominent role in
      working with caregivers, it is necessary to understand young caregivers. DESIGN:
      The population of interest was youngsters aged 10 to 19 caring for adults at home
      with cancer. Eleven children and adolescents in seven families were recruited,
      1993-1994, through purposive sampling from hospices and cancer clinics. METHODS:
      Phenomenologic interviews, ethnographic interviews and selected participant
      observation experiences, and identification of needs through an unstructured
      survey were used. FINDINGS: "Hard, but gratifying" emerged as the dominant
      phenomenologic description of caregiving. Emergent ethnographic themes indicated
      caregiving by children and adolescents was an expectation of family life. School
      and church were described as avenues for social support for youngsters in care
      giving situations. CONCLUSIONS: Youngsters aged 10 to 19 are caring for adults
      with cancer at home. Further descriptive study of youngsters caring for adults
      with cancer is needed.

PMID- 9549936
TI  - Emancipatory potential of storytelling in a group.
AB  - PURPOSE: To examine the health-promoting functions of storytelling in a group of
      women. DESIGN: Secondary analysis, descriptive. A convenience sample of 28 women
      of African descent living in the Seattle-Tacoma region of the United States was
      used. METHODS: Narrative analysis of 115 stories. Data were audio-taped in four
      focus groups convened during a 6-week period in 1992. FINDINGS: Six major
      functions of storytelling were identified: (a) contextual grounding, (b) bonding
      with others, (c) validating and affirming experiences, (d) venting and catharsis,
      (e) resisting oppression, and (f) educating others. CONCLUSIONS: Storytelling is
      useful for learning more about historical and contextual factors affecting the
      well-being of women of African descent and for improving their lives. Group
      storytelling can create an environment that supports evaluation of experience and
      promotes problem-solving.

PMID- 9549937
TI  - Hampton, Nutting, and Rival gospels at The Johns Hopkins Hospital and Training
      School for Nurses, 1889-1906.
AB  - PURPOSE: To examine the attempts by Isabel Hampton Robb and Mary Adelaide Nutting
      to reshape nurse training into an academic system of nursing education. As health
      care delivery undergoes transformation in the 1990s, it is useful to consider the
      strategies used as well as the successes and failures, of past nurse leaders.
      DESIGN: Historical research. METHODS: Archival data were analyzed in 1996
      pertaining to the creation in 1889 and administration of the nursing school and
      hospital founded by Johns Hopkins in Baltimore, Maryland, USA. Events were
      studied using published and unpublished writings by Hampton and Nutting, as well
      as relevant secondary sources. FINDINGS: Separated by class from those with
      power, and limited by 19th century notions of women's place, Isabel Hampton Robb
      and Adelaide Nutting helped inaugurate nursing's quest for professionalization.
      Undaunted by adversity, they achieved novel accomplishments for women and nurses.
      Hampton and Nutting possessed vision, intelligence, the capacity to motivate,
      political skills, good judgement, and managerial competence. CONCLUSIONS:
      Hampton's and Nutting's inability to strengthen the link between the school of
      nursing and the Johns Hopkins University and the lack of unity within nursing
      limited their success. This research illuminates some of the controversies
      pertaining to nursing during an earlier period of sweeping health care change.

PMID- 9549938
TI  - Nursing education and international health in the United States, Latin America,
      and the Caribbean.
AB  - PURPOSE: To identify international health activities in United States, Latin
      American, and Caribbean schools of nursing. In the international community,
      nurses face challenges similar to those in related professions, but without the
      benefit of a long tradition. There is little research about how nursing education
      and associated activities prepare nurses to deal with international health, and
      little information about the extent of international health activities in U.S.
      schools of nursing. DESIGN: Descriptive. METHOD: Using a questionnaire with 16
      items, a survey was conducted in 1995 on a random sample of representatives from
      100 university schools of nursing in the United States plus 15 schools with known
      international activities (10 from the United States and 5 from Latin America and
      the Caribbean). FINDINGS: International health as a program topic was found in
      one-third of U.S. schools of nursing. However, nursing curriculums do not
      integrate international health with other subjects. Also, partnerships with
      foreign institutions are incipient and international health activities are
      usually individual initiatives with little institutional support. CONCLUSIONS:
      For nurses to become major contributors to international health, nursing
      curriculum content must shift from "international nursing" to "international
      health." Programs of nursing education should include study of social, economic,
      and political factors that affect health care systems. Schools should develop
      partnership agreements.

PMID- 9549939
TI  - Around-the-clock nursing care for the elderly in Japan.
AB  - PURPOSE: To describe the first phase of creating a Japanese model of community
      based long-term care, called around-the-clock care (ACC), by operationally
      defining the components of ACC, identifying those eligible for the program,
      clarifying methods of planning and organization, and exploring outcomes. DESIGN:
      Exploratory evaluation for the population of frail elderly Japanese citizens
      living at home. A convenience sample of 44 patients receiving care from four
      visiting-nurse-service stations during 3 months in 1994 was used. METHODS: Needs
      assessments; record reviews of patient encounters; evaluations by patients,
      families, and visiting nurses; and reviews of administrative data. FINDINGS:
      Nurses perceived that ACC stabilized medical status, reduced the emotional and
      physical burden of treatment, and improved hygiene. It also reduced family
      caregiving burdens and the stress of family caregivers' employment
      responsibilities. The highest rating of ACC by patient and families was for those
      with the most complex physical needs. Skilled nursing at home permitted early
      identification and treatment of problems before they became crises or required
      hospitalization. CONCLUSIONS: Early findings suggest 24-hour nurse-home helper
      teamwork may be an effective system of community-based long-term care and should
      be considered a key element of future Japanese health policy.

PMID- 9549940
TI  - Quality health outcomes model. American Academy of Nursing Expert Panel on
      Quality Health Care.
AB  - PURPOSE: Donabedian's 1966 framework of structure, process, and outcome has
      guided three decades of study in the United States of the elements needed to
      evaluate and compare medical care quality. Donabedian's perspective was
      essentially linear, assuming that structures affect processes, which in turn
      affect outcomes. Patient characteristics are sometimes considered as mediating
      outcomes and clinical interventions are considered to be processes. A model is
      presented in the following article that relates multiple factors affecting
      quality of care to desired outcomes. It extends previous models by positing
      dynamic relationships with indicators that not only act upon, but reciprocally
      affect the various components. SCOPE AND SOURCES: The proposed model was derived
      from a synthesis of the authors' experience in quality of care practice and
      research, as well as selected previous theories. CONCLUSIONS: The quality health
      outcomes model is sufficiently broad (a) to guide development of databases for
      quality improvement and outcomes management, (b) to suggest key variables in
      clinical intervention research, and (c) to provide a framework for outcomes
      research and outcomes management that compares not only treatment options, but
      organizational or system level interventions. The model also has several policy
      implications.

PMID- 9549941
TI  - Review of the literature on falls among the elderly.
AB  - PURPOSE: To review and summarize the literature from nursing, medical, and
      ancillary fields on falls among the elderly. Major injuries from falls are
      associated with mortality, especially among the elderly. Researchers indicate
      that, in many cases, falls can be prevented. A summary of the available
      literature provides information which can be used to plan interventions.
      ORGANIZING FRAMEWORK: Over 100 publications, 1979-1996 related to falls by
      elderly were reviewed. Descriptive terms used for searching MEDLINE were falls,
      elderly, and accidents. Literature from several disciplines was reviewed.
      FINDINGS: Fall risk can be predetermined and nursing actions can be taken to
      reduce the occurrence and severity of falls. CONCLUSIONS: To reduce the
      deleterious effects of falls in the elderly, knowledge-based practice is
      essential.

PMID- 9549942
TI  - New definition of mental retardation for the American Association of Mental
      Retardation.
AB  - PURPOSE: To describe the new definition of mental retardation developed by the
      American Association of Mental Retardation (AAMR) published in 1992. The previous
      definition was based on a deficiency model that identified "subaverage
      intelligence" using an intelligence quotient (IQ) score equal to or less than 70.
      The new definition places greater emphasis on adaptive skills and environmental
      support needs. SCOPE: Defining mental retardation according to AAMR criteria
      reflects a significant paradigm shift from an absolute trait to a functional
      conception. The new definition is dynamic, attends to context, is inherently
      holistic--and, therefore--closely aligned with nursing theory. Diagnosis is a
      three-step process by which functional strengths and weaknesses are identified
      along 4 dimensions and 10 adaptive-skill areas. Identification of needed supports
      is incorporated within the three-step process. CONCLUSIONS: Nurses can enhance
      holistic care by working to have AAMR's new definition adopted by government
      legislators and administrators of state and county agencies that provide mental
      retardation services. Nurses should become active participants as
      interdisciplinary diagnostic team members as well as case managers. Nurse
      researchers and educators can contribute toward further developing AAMR's
      definition by standardizing assessment instruments, working to make diagnostic
      procedures more user-friendly, and researching the construct validity of adaptive
      skill areas. Finally, nurses should help legislators and policy makers understand
      the sociocultural ramifications of AAMR's new definition.

PMID- 9549943
TI  - Adapting to and managing diabetes.
AB  - PURPOSE: To advance understanding of the lived experience of diabetes as
      described in published research and theses. Meta-analysis extends the analysis of
      individual research studies beyond individual experience to incorporate dominant
      system beliefs and health system ideologies. ORGANIZING FRAMEWORK: Curtin and
      Lubkin's (1990) conceptualization of the experience of chronic illness. SOURCES:
      Forty-three qualitative interpretive research reports in six computerized data
      bases 1980-1996 pertaining to the lived experience of diabetes and published in
      nursing, in the social sciences, and in allied health journals were used.
      METHODS: Meta-ethnography in which trustworthiness was achieved by using multiple
      researchers, identifying negative or disconfirming cases, and testing rival
      hypotheses FINDINGS: Balance is the determinant metaphor of the experience of
      diabetes. People learn to balance diabetes through their experience and
      experimentation with strategies for managing their illness. CONCLUSIONS: Learning
      to balance is a developmental process in which one learns to assume control of
      diabetes management. Support for such development requires that nurses know their
      clients as individuals and value the expertise they have gained in living with
      diabetes. Control of blood sugar levels within a prescribed range may be a goal
      established by professionals, but the goal of healthy balance determines a
      person's willingness to assume an active role in self-care.

PMID- 9549944
TI  - Conceptualization and measurement of doing family caregiving well.
AB  - PURPOSE: To review progress in the conceptualization and measurement of five
      concepts related to doing family caregiving well: caregiving mastery, self
      efficacy, competence, preparedness, and quality. Families are increasingly
      involved in providing complex care to ill or aged family members at home. Their
      ability to do caregiving well is vitally important and a focus of nursing
      practice in many clinical settings. ORGANIZING FRAMEWORK: Concepts were organized
      into two groups: those that refer to caregivers' perceptions of how well they are
      providing care and those that refer to professional assessment of the quality of
      care provided. SOURCES: Family caregiving literature from nursing, gerontology,
      psychology, and social work, 1987-1996. FINDINGS: There is growing interest in
      doing family caregiving well. However, research in this area is limited by the
      current state of development of ideas and measures. CONCLUSIONS: Two issues that
      should be addressed to advance research are the perspective taken on doing
      caregiving well and change over time in doing caregiving well.

PMID- 9549945
TI  - Nursing model of hospitalization events.
AB  - PURPOSE: To provide a model of hospitalization events from a nursing perspective.
      Hospitalization has become an event of highly technical care coupled with intense
      nursing care requirements. This proposed model is needed to support clinical
      nursing research among hospitalized patients. SCOPE: Hospitalization occupying
      space and time as a discrete event on the health-illness continuum. First
      developed to provide a framework for a descriptive study, the model shows the
      factors involved in hospitalization and provides a framework for understanding
      the nursing care that occurs. Selected results from descriptive research that
      used patients hospitalized with AIDS as subjects are reported as an example of
      use of the model. CONCLUSIONS: Research about hospitalization events continues to
      be critical for the advancement of clinical nursing. This model is presented to
      provide a conceptual framework for future research.

PMID- 9549946
TI  - Using literature to create cultural competence.
AB  - PURPOSE: To describe how literature can be used to promote cultural competence.
      Cultural competence is essential for nurses who practice in diverse societies
      like the United States. ORGANIZING FRAMEWORK: Cultural competence is viewed as a
      dynamic process of framing assumptions, knowledge, and meanings from a culture
      other than one's own. Selected excerpts from "The Color Purple" by Alice Walker
      are used to illustrate the method. Isler's readers' response theory serves as a
      guide for imaginative engagement and reflective discussion of the concept of
      health. CONCLUSIONS: Literature helps to dispel the false notion of a monolithic
      culture. Reflecting on reputable literature helps us hear the stories of those we
      hope to help and heal.

PMID- 9549947
TI  - Professional, ethical, and legal implications for spiritual care in nursing.
AB  - PURPOSE: To highlight nurses' professional and ethical responsibility to
      consistently provide spiritual care. The legal issue of nurse-client privilege in
      relation to spiritual care is also discussed. Spiritual care is consistent with
      the model of holistic care. Yet spiritual care often remains a neglected focus of
      current nursing practice. CONCLUSIONS: Spirituality, as an important aspect of
      wellness, is indispensable in nursing care. Nurses are obligated to take an
      active role in meeting the spiritual needs of patients.

PMID- 9549948
TI  - Nurses, indirect trauma, and prevention.
AB  - PURPOSE: To begin examining the nature of vicarious or indirect trauma and to
      discuss risk factors and prevention strategies. Despite the fact that many nurses
      are traumatized indirectly, few recognize the insidious development of such
      trauma. The dynamics of indirect trauma are relevant to nursing as are risk
      factors and prevention strategies. SCOPE: Brief review of the literature (1974
      1997) on vicarious trauma, compassion fatigue, secondary traumatic stress
      disorder, and traumatic countertransference using short vignettes for
      illustration. CONCLUSION: Nurses who are informed about vicarious trauma and who
      actively maintain a balanced personal and professional life are in the best
      position to bring themselves and their clients through the many hazards of trauma
      work. The implications of vicarious or indirect trauma for nurses and clients are
      serious and complex requiring thoughtful analysis and research to clarify its
      effects.

PMID- 9549949
TI  - Definition of ADHD.

PMID- 9549950
TI  - Medication for learning disorders.

PMID- 9549952
TI  - Stimulant use and trichotillomania.

PMID- 9549953
TI  - Obsessive-compulsive disorder and separation anxiety.

PMID- 9549951
TI  - Mania in young children.

PMID- 9549954
TI  - Anorexia nervosa and bulimia nervosa in children and adolescents: a review of the
      past 10 years.
AB  - OBJECTIVE: To critically review the research in juvenile anorexia nervosa and
      bulimia nervosa over the past 10 years and highlight recent advances in normal
      development as it pertains to these disorders and their diagnosis, prevention,
      and treatment. METHOD: Computerized search methods were combined with manual
      searches of the literature. A detailed review of the most salient articles is
      provided. Preference was given to studies involving children and adolescents that
      approached the subject from a developmental perspective. RESULTS: The information
      from these studies is presented in a developmental framework. Research in eating
      disorders has progressed, but definitive longitudinal data are still absent from
      the literature. Research specific to treatment of child and adolescent eating
      disorders remains rare. CONCLUSIONS: Data approaching eating disorders from a
      developmental perspective are available in only a few studies. Research is needed
      addressing normative data on the development of eating behavior and specific risk
      and resilience factors for pathology in specific developmental periods.
      Especially lacking are studies regarding the continuities and discontinuities of
      eating disturbances across the life span. Best documented are epidemiological
      studies of prevalence and incidence, long-term outcome in anorexia nervosa, and
      short-term treatment response in bulimia.

PMID- 9549955
TI  - Commentary: unmasked and uncontrolled medication trials in child and adolescent
      psychiatry.

PMID- 9549956
TI  - An open clinical trial of buspirone in children with attention
      deficit/hyperactivity disorder.

PMID- 9549957
TI  - An open trial of risperidone in young autistic children.
AB  - OBJECTIVE: To assess the benefits and side effects of risperidone in young
      autistic children. METHOD: In this open, prospective trial, subjects were treated
      with risperidone for 12 weeks. All subjects were started at 0.5 mg daily with
      individual titration to a maximum of 6 mg or 0.1 mg/kg daily. Behavioral ratings,
      completed by the investigators and the children's parents, included the Clinical
      Global Impressions (CGI), Children's Psychiatric Rating Scale, Conners Parent
      Teacher Questionnaire, Childhood Autism Rating Scale, and Abnormal Involuntary
      Movement Scale. RESULTS: Ten boys, aged 4.5 to 10.8 years, were enrolled in the
      study and all completed the 12-week protocol. The mean final dose was 1.3 mg/day
      (range = 1 to 2.5 mg/day). On the basis of CGI-rated improvement, 8 of the 10
      children were considered to be responders. Improvement was also demonstrated on
      the other scales. Transient sedation was common, and the children gained an
      average of 3.5 kg over the 12 weeks of the study. There was no evidence of either
      extrapyramidal symptoms or tardive dyskinesia. CONCLUSIONS: These results suggest
      that risperidone may be safe and leads to improvements in several behavioral
      symptoms in young children with autism. Controlled studies of risperidone in
      young autistic children are warranted.

PMID- 9549958
TI  - Childhood-onset schizophrenia: an open-label study of olanzapine in adolescents.
AB  - OBJECTIVE: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with
      anticholinergic activity, has a profile of known receptor affinity similar to
      that of clozapine. This pilot study examined the efficacy of olanzapine for
      treatment-refractory childhood-onset schizophrenia in eight patients who had
      received 8-week open-label trials. For comparison, data are included from 15
      patients who had received 6-week open-label clozapine trials using identical
      rating instruments (largely by the same raters) in the same treatment setting.
      METHOD: Twenty-three children and adolescents with an onset of DSM-III-R
      schizophrenia by age 12 for whom at least two different typical neuroleptics had
      been ineffective participated in the two separate studies. Some of the patients
      were intolerant of clozapine, although it had been effective (n = 4). Patients
      receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric
      Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale
      for the Assessment of Negative Symptoms, and the Clinical Global Impressions
      Scale for Improvement. RESULTS: For the eight patients who received olanzapine
      trials, at week 8 there was a 17% improvement in the BPRS total score, a 27%
      improvement in the Scale for the Assessment of Negative Symptoms, and a 1%
      improvement in the Scale for the Assessment of Positive Symptoms, relative to
      "ideal" admission status on typical neuroleptics. In contrast, the magnitude of
      the effect sizes for each of the clinical ratings was larger at week 6 of the
      previous clozapine trial than for an 8-week olanzapine trial, relative to
      admission status on typical neuroleptics. For the four children who had received
      both clozapine and olanzapine, BPRS total scores were significantly lower at week
      6 of clozapine treatment compared with week 6 of olanzapine treatment (p = .03).
      CONCLUSION: These data provide preliminary evidence for the efficacy of
      olanzapine for some children and adolescents with treatment-refractory
      schizophrenia, but they also suggest the need for a more rigorous double-blind
      comparison of these two atypical antipsychotics.

PMID- 9549959
TI  - Sertraline treatment of children and adolescents with obsessive-compulsive
      disorder or depression: pharmacokinetics, tolerability, and efficacy.
AB  - OBJECTIVE: To evaluate the pharmacokinetics, safety, and efficacy of sertraline
      in children (6 to 12 years old) and adolescents (13 to 17 years old). METHOD:
      Children (n = 29) and adolescents (n = 32) with major depression, obsessive
      compulsive disorder (OCD), or both received a single dose of 50 mg of sertraline
      followed, 1 week later, by 35 days of sertraline treatment as follows: (1) either
      a starting dose of 25 mg/day titrated to 200 mg/day in 25-mg increments or (2) a
      starting dose of 50 mg/day titrated to 200 mg/day in 50-mg increments. Sertraline
      and desmethylsertraline pharmacokinetics were determined approximately weekly,
      and efficacy measures were assessed before drug administration and at the end of
      treatment. RESULTS: Mean area under the plasma concentration-time curve (AUC),
      peak plasma concentration (Cmax), and elimination half-life (t1/2) for sertraline
      and desmethylsertraline were similar to previously reported adult values. No
      titration-dependent pharmacokinetic or safety differences were seen. While Cmax
      and AUC0-24 were greater for children versus adolescents, these differences
      disappeared after parameters were normalized for body weight. Sertraline was well
      tolerated in both children and adolescents, with adverse experiences similar to
      those previously reported by adult patients. Efficacy measurements indicated
      improvement (p < .001) in depression and OCD symptomatology. CONCLUSIONS:
      Sertraline can be safely administered to pediatric patients using the currently
      recommended adult titration schedule.

PMID- 9549960
TI  - Cognitive-behavioral treatment of school-refusing children: a controlled
      evaluation.
AB  - OBJECTIVE: To evaluate the efficacy of a 4-week cognitive-behavioral treatment
      program for children who refuse to go to school. METHOD: Thirty-four school
      refusing children (aged 5 to 15 years) were randomly assigned to a cognitive
      behavioral treatment condition or a waiting-list control condition. Treatment
      consisted of individual child cognitive-behavioral therapy plus parent/teacher
      training in child behavior management skills. Measures taken before and after
      treatment included school attendance, child self-report of emotional distress and
      coping, caregiver reports on emotional and behavioral problems, and clinician
      ratings of global functioning. RESULTS: Relative to waiting-list controls,
      children who received cognitive-behavioral therapy exhibited a significant
      improvement in school attendance. These children also improved on self-reports of
      fear, anxiety, depression, and coping. Significant improvements also occurred in
      relation to caregiver reports and clinician ratings. Maintenance of therapeutic
      gains was demonstrated at a 3-month follow-up assessment. CONCLUSIONS: Cognitive
      behavioral treatment of school refusal was efficacious and acceptable. The
      relative contributions of child therapy and parent/teacher training require
      further study.

PMID- 9549961
TI  - Cognitive-behavioral treatment of school phobia.
AB  - OBJECTIVE: To conduct a controlled group outcome investigation of the efficacy of
      cognitive-behavioral treatment for school phobia. METHOD: Fifty-six children with
      school phobia were randomly assigned to 12 weeks of cognitive-behavioral therapy
      or an attention-placebo control condition. Pre- and posttreatment school
      attendance, self-reported anxiety and depression, and diagnostic status were
      compared. RESULTS: Both the experimental and control treatments were equally
      effective at returning children to school. Both treatments also were effective in
      reducing children's anxiety and depressive symptoms. Follow-up revealed no
      differences between groups when the children reentered school the next school
      year. CONCLUSIONS: Overall, results suggest that psychosocial treatments are
      effective at returning school-phobic children to school and that the highly
      structured cognitive-behavioral approach may not be superior to more traditional
      educational and supportive treatment methods.

PMID- 9549962
TI  - Cognitive-behavioral treatment of pediatric obsessive-compulsive disorder: an
      open clinical trial.
AB  - OBJECTIVE: The purpose of this open clinical trial was to examine the efficacy of
      cognitive-behavioral treatment involving exposure and ritual prevention for
      pediatric obsessive-compulsive disorder (OCD). METHOD: Children and adolescents
      with diagnosed OCD (N = 14) received cognitive-behavioral treatment, seven
      patients received intensive treatment (mean = 18 sessions over 1 month) and seven
      received weekly treatment (mean = 16 sessions over 4 months). Eight of these
      patients received concurrent treatment with serotonin reuptake inhibitors and six
      received cognitive-behavioral treatment alone. Outcome was assessed via
      interviewer ratings on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS),
      Obsessive Compulsive Rating Scales for Main Fear and Main Ritual, and Hamilton
      Depression Rating Scale. RESULTS: Cognitive-behavioral treatment was effective in
      ameliorating OCD symptoms. Twelve of the 14 patients were at least 50% improved
      over pretreatment Y-BOCS severity, and the vast majority remained improved at
      follow-up; mean reduction in Y-BOCS was 67% at posttreatment and 62% at follow-up
      (mean time to follow-up = 9 months). CONCLUSIONS: Results suggest that cognitive
      behavioral treatment by exposure and ritual prevention is effective for pediatric
      OCD. Controlled studies with random assignment to conditions are warranted to
      evaluate the relative efficacy of cognitive-behavioral pharmacological, and
      combined treatments.

PMID- 9549963
TI  - Is juvenile obsessive-compulsive disorder a developmental subtype of the
      disorder? A review of the pediatric literature.
AB  - OBJECTIVE: To examine the clinical correlates of obsessive-compulsive disorder
      (OCD) in children and adolescents. METHOD: A systematic review of the extant
      literature on juvenile OCD was conducted examining age at onset, gender
      distribution, symptom phenomenology, psychiatric comorbidity, neurological and
      perinatal history, family psychiatric history, cognitive and neuropsychological
      profiles, and treatment and outcome in juvenile OCD subjects. RESULTS: Juvenile
      OCD was associated with a unique peak of age at onset indicating a bimodal
      incidence of the disorder, male preponderance, a distinct pattern of comorbidity
      with attention-deficit/hyperactivity disorder and other developmental disorders
      as well as frequent associated neuropsychological deficits, an increased familial
      loading for OCD, and frequent absence of insight. CONCLUSION: These findings show
      that juvenile OCD is associated with a unique set of correlates that appear to
      differ from findings reported in studies of adult OCD subjects. Although in need
      of confirmation, these findings suggest that juvenile OCD may be a developmental
      subtype of the disorder. Since juvenile OCD is likely to continue into adulthood,
      these findings stress the importance of considering age at onset in clinical and
      research studies of adults with OCD.

PMID- 9549964
TI  - Individual and familial predictors of impairment in childhood anxiety disorders.
AB  - OBJECTIVE: To determine which correlates of childhood anxiety disorders are
      predictive of impaired functioning as judged by clinicians. METHOD: Seventy-four
      families of children with anxiety disorders attending a hospital outpatient
      clinic completed questionnaires measuring child symptoms of anxiety and
      depression, maternal psychopathology, maternal ratings of child psychopathology,
      and developmental and environmental difficulties. Clinicians completed the Global
      Assessment of Functioning (GAF) for each child, and correlations between it and
      the other measures were ascertained. RESULTS: Maternal ratings of child conduct
      problems, child symptoms of depression, maternal phobic anxiety, developmental
      difficulties, and psychosocial adversity were significantly correlated with GAF.
      Results of a multiple regression analysis revealed that these variables accounted
      for 25% of the variance in GAF scores. The first four variables were significant
      predictors of impairment in children with phobic disorders. Psychosocial
      adversity was the only significant predictor of impairment in children with
      generalized anxiety disorder. CONCLUSIONS: In addition to child depression and
      developmental or psychosocial adversity, impairment in childhood anxiety
      disorders appears to be related to parental anxiety and behavior management
      difficulties, particularly in phobic disorders. Addressing the latter factors may
      enhance treatment efficacy.

PMID- 9549965
TI  - Validity of DSM-IV subtypes of conduct disorder based on age of onset.
AB  - OBJECTIVE: To present data from the DSM-IV field trials that led to the
      distinction between subtypes of conduct disorder (CD) that emerge in childhood or
      adolescence. In addition, data from a household sample were used to attempt to
      cross-validate these findings. METHOD: Differences between youths who met
      criteria for the two subtypes of CD were examined in the field trials sample of
      440 youths aged 4 through 17 years and in a household sample of 1,285 youths aged
      9 through 17 years. RESULTS: In both samples, there was a steep decline in
      aggression occurring around an age of onset of 10 years, but the number of
      nonaggressive behaviors was unrelated to the age of onset of CD. In the field
      trials sample, youths who met criteria for the adolescent-onset type were more
      likely to be girls, less likely to meet criteria for oppositional defiant
      disorder, and less likely to have a family history of antisocial behavior than
      the childhood-onset type, but these latter findings were not confirmed in the
      household sample. CONCLUSIONS: The DSM-IV approach to subtyping CD distinguishes
      subgroups that differ markedly in level of physical aggression. The advantages of
      a developmental approach to subtyping are discussed.

PMID- 9549966
TI  - Case study: behavioral treatment of obsessive-compulsive disorder in a boy with
      comorbid disruptive behavior problems.
AB  - Comorbid psychiatric conditions often complicate the treatment of childhood
      obsessive-compulsive disorder (OCD). Behavioral treatment of OCD using exposure
      plus response prevention for a boy with disruptive behavior disorders and two
      previous unsuccessful medication trials is described. Treatment was adapted to
      his developmental level, his mother was highly involved in treatment, and a
      contingency management program contained his disruptive behavior so that he could
      participate in therapy. Posttreatment and 2- and 6-month follow-up measures
      indicated marked improvement in OCD symptoms. The possibility of successful
      behavioral treatment of OCD in medication-free children with disruptive behavior
      problems is highlighted.

PMID- 9549967
TI  - Cytochromes: a primer for child and adolescent psychiatrists.

PMID- 9549968
TI  - Development of the cerebral cortex: IV. Transcription factors.

PMID- 9549969
TI  - CDC reports first-ever decline in AIDS diagnoses--treatment and prevention
      advances spur new trend.

PMID- 9549970
TI  - Instilling happiness into medical school. The University of Arkansas College of
      Medicine's Medical Student Mental Health Program.
AB  - The University of Arkansas for Medical Sciences (UAMS), College of Medicine's
      Medical Student Mental Health Services Program, initiated in 1992, has grown into
      a comprehensive, readily accepted service utilized by one out of four medical
      students during their matriculation. Students rely on the service to help them
      with a wide variety of issues and feel secure that their care is confidential.

PMID- 9549971
TI  - Cardiac AL-amyloidosis in multiple myeloma.

PMID- 9549972
TI  - Radiological case of the month. Adrenal adenoma.

PMID- 9549973
TI  - Tumor necrosis factor alpha.

PMID- 9549974
TI  - Acanthosis, albumin, and cancer.

PMID- 9549975
TI  - Teenage pregnancy.

PMID- 9549976
TI  - Intra-aortic balloon pump: indications and complications.
AB  - Results obtained with intra-aortic balloon pumps (IABPs) at Harbor-UCLA Medical
      Center from 1990 to 1995 were reviewed to analyze the indications for its use as
      well as the incidence and types of vascular complications that occurred. Of 86
      patients (53 men and 33 women) in whom pumps were used, 66 underwent coronary
      bypass, 14 underwent valve replacement, and 6 underwent both coronary
      bypass/valve replacement. Thirteen (15%) deaths occurred (8 coronary bypass
      patients, 4 valve replacement patients, and 1 coronary bypass/valve replacement
      patient). The indications for IABP were broadly classified as prophylactic or
      inability to wean. Prophylactic IABP placement preoperatively occurred in 35
      (41%) patients for profound ventricular dysfunction (27 patients), compelling
      coronary anatomy including critical left main disease (7 patients), and unstable
      angina (1 patient). Inability to wean occurred in 51 (59%) patients. Three
      patients (3.5%) developed major vascular complications resulting in limb
      ischemia. All three underwent thrombectomies, fasciotomies, and above-knee
      amputations; two patients subsequently died. Vascular reconstruction was
      performed in two patients as a direct result of their vascular process. All three
      vascular complications occurred in women. Besides gender, there was no difference
      between IABP patients with or without vascular complications in terms of age or
      presence of diabetes, hypertension, smoking history, obesity, or known peripheral
      vascular disease. These results indicate that IABPs are effective both
      prophylactically and intraoperatively in patients who would not otherwise survive
      cardiac surgery.

PMID- 9549977
TI  - The recruitment triangle: reasons why African Americans enroll, refuse to enroll,
      or voluntarily withdraw from a clinical trial. An interim report from the African
      American Antiplatelet Stroke Prevention Study (AAASPS).
AB  - Recruitment and retention of study subjects are key to the success of a clinical
      trial. In the case of minority patients, this may be challenging as minority
      patients have been underserved by the medical health-care system. Furthermore,
      minority patients are more likely to experience barriers to entry into a clinical
      trial such as mistrust of the medical system, economic disadvantages, lack of
      awareness of study programs, and communication barriers. An open-ended
      questionnaire was used to determine reasons why subjects in the African-American
      Antiplatelet Stroke Prevention Study (AAASPS) remained in the study or
      voluntarily withdrew in the absence of an adverse event. Potential enrollees who
      refused to participate in the AAASPS also were queried. Enrollees who remained in
      the program consistently stated that they participated to reduce the risk of
      stroke recurrence and to help others by finding a "cure" for stroke. Those who
      withdrew or refused to participate consistently stated that they were afraid of
      being used as "guinea pigs." A "recruitment triangle" emerged that might predict
      a patient's likelihood of participation in a clinical trial. The sides of the
      triangle include the patient, key family members and friends, and the primary
      medical doctor and other medical personnel. The organizers of a clinical trial
      need to be aware of the "recruitment triangle" and establish strategies to
      heighten and maintain its integrity.

PMID- 9549978
TI  - Diabetes mellitus and its complications in an African-American community: project
      DIRECT.
AB  - Project DIRECT (Diabetes Intervention Reaching and Educating Communities
      Together) is a multilevel community-based intervention project designed to
      address diabetes and its complications in an African-American community. This
      article presents results of the Project DIRECT pilot study and describes risk
      factors for diabetes, diabetes prevalence, complications, and care practices.
      During 1993, a pilot study was conducted among persons 20 to 74 years of age in
      Wake County, North Carolina. The study involved household interviews and
      examinations, and more extensive health center interviews and examinations based
      on the race of the head of the household, previous diagnosis of diabetes, and
      results of capillary glucose tests done in the household. Of the black population
      aged 20 to 74 years, 52 +/- 3% reported being inactive and 51 +/- 3% were
      overweight; the prevalence of diagnosed diabetes was 5.2 +/- 0.9%; the prevalence
      of undiagnosed diabetes was 5.7 +/- 2.7%; and the prevalence of impaired glucose
      tolerance was 11.4 +/- 7.5%. Blacks with diabetes were significantly more likely
      than nonblacks with diabetes to have uncontrolled hypertension and to smoke
      cigarettes. Blacks with diabetes were significantly less likely to report having
      health insurance or to have a private health-care provider. Diabetes mellitus is
      a major public health problem in the African-American community of Wake County.
      Modifiable risk factors for diabetes and undiagnosed diabetes are common. Project
      DIRECT is attempting to improve the health-related quality of life of this
      population by reducing the burden of diabetes and its complications through a
      multilevel, community-based intervention.

PMID- 9549979
TI  - Increased circulating levels of soluble HLA class I heterodimers in patients with
      sickle cell disease.
AB  - This study examined the presence of a persistent state of low-grade inflammation
      in sickle cell anemia patients by measuring circulating sHLA-I heterodimers and C
      reactive protein during the steady state and after recent crises. Thirty-nine
      pediatric sickle hemoglobinopathy patients were studied during the steady state
      and 11 patients were evaluated within 1 month of a painful crisis. A disease
      severity score was generated for each patient, and soluble HLA-I (sHLA-I) and C
      reactive protein levels were determined. Soluble HLA-I was significantly elevated
      in 55% of the steady-state group and in 36% of the recent-crisis group. The
      percentage of patients with elevated sHLA-I differed in the various disease
      subgroups in the steady state: 46% of Hb SS patients, 70% of Hb SC patients, 75%
      of Hb S beta-thal patients, and 20% of Hb SSF patients. Steady-state and recent
      crisis sHLA-I levels were not significantly different. C-reactive protein levels
      were elevated in 11% of steady-state patients and in 9% of recent-crisis
      patients. Soluble HLA-I levels did not correlate with C-reactive protein levels
      or disease severity score, age, hemoglobin, reticulocyte count, platelet count,
      or white cell count. These results show that the majority of sickle
      hemoglobinopathy patients have elevated sHLA-I levels during the steady state and
      after recent crisis, suggesting the presence of chronic inflammation during the
      steady state.

PMID- 9549981
TI  - Measurement of self-esteem in repeat assault victims.
AB  - Background characterization of assault-related injuries have demonstrated that
      lifestyle, substance abuse, education, employment, mental illness, and high-risk
      behavior contribute to low self-esteem in repeat assault victims. Recurrent
      assault patients have never been studied with respect to self-esteem. This study
      evaluated self-esteem and assault-related injury in 28 consecutive male assault
      patients (11 first-assault and 17 recurrent-assault patients) and 19 controls
      with no previous assault history. Study participants were administered the Walmyr
      Assessment Scales Index of Self-Esteem (WASISE) as part of a three-item survey to
      determine the relationship between self-esteem and assault-related injury. No
      demographic differences were found between the groups. The mean (+/- standard
      error) WASISE score for recurrent-assault patients (34.9 +/- 3.4) was
      significantly higher than mean scores for no-assault and first-time assault
      injured patients (14.7 +/- 1.4 and 15.0 +/- 2.3, respectively). The recurrent
      assault patients had a lower mean education level than both no-assault and first
      time assault-injured patients (2.1 +/- 0.26 and 1.9 +/- 0.57, respectively).
      Eighteen (2%) first-time assault-injured and 11 (7%) recurrent-assault patients
      were employed. These data suggest that self-esteem, education, and employment
      history need to be considered when evaluating and developing interventions for
      repeat-assault patients.

PMID- 9549980
TI  - Cultural sensitivity and readability of breast and prostate printed cancer
      education materials targeting African Americans.
AB  - Cancer prevention materials such as pamphlets, booklets, and fact sheets play a
      significant role in reducing cancer disparities. Little is documented in the
      literature about the cultural sensitivity of materials targeting African
      Americans. The Cancer Prevention Materials and African Americans project was
      conducted to assess the cultural sensitivity and readability of printed cancer
      education materials targeting African Americans. Results showed current breast
      and cancer materials are not written at appropriate reading levels, and only 54%
      of the breast and 40% of the prostate cancer materials were found to be
      culturally sensitive. Even though the materials are being developed and
      disseminated in health fairs, physician offices, barber shops, and other
      locations, the materials are still not reflective of the African-American
      populations and do not consider literacy, visual, written messages, and format as
      factors in their utilization. Future studies should assess the appropriateness of
      materials for African Americans to promote and prevent cancer in African
      Americans.

PMID- 9549983
TI  - Fiberoptic bronchoscopic removal of intratracheal pledgetted repair sutures.
AB  - This article describes the use of a flexible bronchoscope to remove pledgetted
      repair sutures within the trachea. The use of a flexible scope to remove densely
      adherent material is difficult but occasionally necessary.

PMID- 9549982
TI  - Postpartum surveillance of bacteriuria in term vaginal deliveries.
AB  - This study examined the prevalence of bacteriuria in early postpartum period
      after term vaginal delivery in Trinidad, West Indies. Asymptomatic bacteriuria
      occurred in 58 (34.5%) of 168 patients tested. The prevalence of bacteriuria was
      significantly higher in non-catheterized patients than in catheterized patients
      and occurred more commonly in patients who were 20 to 29 years old and who were
      primigravida rather than multigravida. Forty-four patients had a history of
      urinary tract infection; 18 (40.9%) of these patients had positive urine
      cultures. Although 10 patients had a vaginal discharge in the late third
      trimester, none presented with postpartum bacteriuria. Because of the high
      prevalence of postpartum bacteriuria and the potential to progress to
      pyelonephritis and chronic renal disease, quantitative urine cultures for all
      postnatal patients and curative treatment for all positive cultures are
      recommend.

PMID- 9549984
TI  - A look at oral health within the context of diverse populations: foreword.

PMID- 9549985
TI  - Ethnicity, aging, and oral health outcomes: a conceptual framework.
AB  - An expanded version of Andersen's Behavioral Model of Health Services Utilization
      is used as the theoretical and analytical framework for the International
      Collaborative Study of Oral Health Outcomes (ICS-II). The conceptual framework
      for understanding determinants of oral health is based on a "systems"
      perspective. The framework posits that characteristics of the external
      environment, the dental care delivery system, and the personal characteristics of
      the population influence oral health behaviors. The expanded behavioral model
      conceptualizes health behaviors (oral hygiene practices and dental services
      utilization) as intermediate dependent variables, which in turn influence oral
      health outcomes (evaluated, perceived, patient satisfaction). The framework is
      presented with an increased focus on the effects of race-ethnicity and age
      cohort, the major exogenous variables used in this study for systematic
      assessment of the differences in the multitude of factors influencing oral
      health. The framework can be applied by policy analysis and health services
      managers to help describe, predict, and explain population-based health behaviors
      and health outcomes.

PMID- 9549986
TI  - ICS-II USA research locations: environmental, dental care delivery system, and
      population sociodemographic characteristics.
AB  - Secondary data sources are used to describe the ICS-II USA research locations in
      terms of external environment, dental care delivery system, and population
      sociodemographics. The Native American reservations located in Arizona, New
      Mexico, and South Dakota were rural, while the other research locations were
      primarily urban. Baltimore, Maryland, and the Native American communities had
      fluoridated water, but San Antonio did not. Dental services in Baltimore and San
      Antonio were predominantly financed by private sources, with a small public
      health component. Dental care services in Native American communities were
      largely Indian Health Services (IHS) financed by the US Government. Each
      geographical area exhibited diverse characteristics indicating unique challenges
      for the delivery of community and clinical dental services.

PMID- 9549987
TI  - ICS-II USA research design and methodology.
AB  - The purpose of the WHO-sponsored International Collaborative Study of Oral Health
      Outcomes (ICS-II) was to provide policy-markers and researchers with detailed,
      reliable, and valid data on the oral health situation in their countries or
      regions, together with comparative data from other dental care delivery systems.
      ICS-II used a cross-sectional design with no explicit control groups or
      experimental interventions. A standardized methodology was developed and tested
      for collecting and analyzing epidemiological, sociocultural, economic, and
      delivery system data. Respondent information was obtained by household
      interviews, and clinical examinations were conducted by calibrated oral
      epidemiologists. Discussed are the sampling design characteristics for the USA
      research locations, response rates, samples size for interview and oral
      examination data, weighting procedures, and statistical methods. SUDAAN was used
      to adjust variance calculations, since complex sampling designs were used.

PMID- 9549988
TI  - Predisposing, enabling, and need for dental treatment characteristics of ICS-II
      USA ethnically diverse groups.
AB  - Personal characteristics (predisposing, enabling, and need) are described for the
      population-based samples of adults interviewed in the International Collaborative
      Study of Oral Health Outcomes (ICS-II) USA research locations. Differences in
      sample characteristics are compared by ethnic group (African-American, Native
      American, Hispanic, and White) and age cohort (35-44 and 65-74 years old) by
      means of Bonferroni multiple-means tests and Student's t tests. Differences in
      the personal characteristics of these diverse comparison groups abound. Bivariate
      results indicated that White adults from both age cohorts had higher
      socioeconomic levels, more positive self-rated health status, and greater
      proportions of individuals with dental benefits. Lakota adults from both age
      cohorts reported lower self-rated health status and were most likely to report
      total tooth loss. Hispanic persons were significantly less likely to report a
      usual source of dental care or dental benefits. Need for dental treatment (oral
      pain and oral symptoms index) was generally higher amng Native American and
      Hispanic groups. It is critical that the differences highlighted between the
      among these groups be studied in appropriate strategies for improving the oral
      health of USA adults are to be determined.

PMID- 9549989
TI  - Oral health beliefs in diverse populations.
AB  - Using data from population-based samples of adults participating in the ICS-II
      USA study, and using principal components analysis, we constructed oral health
      belief measures corresponding to the Health Belief Model (HBM) dimensions. Tests
      of validity and reliability were performed. Scales measuring perceived benefit of
      preventive practices and seriousness of oral disease had the highest validity and
      reliability. We used multiple regression analysis to examine sociodemographic
      predictors of perceived benefits of preventive practices. Race-ethnicity and age
      cohort were significant predictors among Baltimore and San Antonio adults. White
      adults and middle-aged persons in both research locations were more likely to
      believe in the benefit of preventive practices. Female gender, higher educational
      attainment, and better self-rated health were significant indicators of more
      positive oral health beliefs in every research location. Results also
      characterize persons who place lower value on preventive practices (i.e., males,
      less-educated persons, and those reporting poorer self-rated health). The design
      of effective dental public health messages and outreach efforts requires an
      analysis of the individual's health orientation and the factors influencing oral
      health beliefs. Oral health education interventions designed to improve health
      beliefs should contain an evaluation component for assessing the impact of
      education on health practices and oral health status.

PMID- 9549990
TI  - Socio-behavioral determinants of oral hygiene practices among USA ethnic and age
      groups.
AB  - In this study, socio-behavioral determinants of oral hygiene practices were
      examined across several dentate ethnic and age groups. Oral hygiene scale scores
      were constructed from toothbrushing and dental floss frequencies self-reported by
      population-based samples of middle-aged (35-44 years) and older (65-74 years)
      dentate adults representing Baltimore African-American and White, San Antonio
      Hispanic and non-Hispanic White, and Navajo and Lakota Native American persons
      participating in the WHO International Collaborative Study of Oral Health
      Outcomes (ICS-II) survey. Female gender, education, certain oral health beliefs,
      household income, and the presence of a usual source of care were revealed with
      multivariate analysis to show a significant positive relationship with higher
      oral hygiene scale scores (indicating better personal oral hygiene practices).
      Other socio-behavioral variables exhibited a more varied, ethnic-specific pattern
      of association with oral hygiene scale scores.

PMID- 9549991
TI  - Determinants of dental care utilization for diverse ethnic and age groups.
AB  - Dental services utilization in the past 12 months was compared across population
      based samples of African-American, Navajo, Lakota, Hispanic, and White adults
      participating in the WHO International Collaborative Study of Oral Health
      Outcomes (ICS-II) at USA research locations. Bivariate results revealed that
      ethnic minority groups in both age cohorts reported significantly fewer dental
      visits in the past 12 months compared with White adults. When dentate status was
      controlled for, age cohort differences were not significant in Baltimore (African
      American and White) and San Antonio (Hispanic and White) research locations. In
      contrast, older Native Americans (65-74 years) reported visiting the dentist
      significantly less often compared with their middle-aged (35-44 years)
      counterparts. Multivariate results indicated that generalizable variables were
      associated with dental contact in every ICS-II USA ethnic group (i.e., dentate,
      usual source of dental care, oral pain). Among the diverse ethnic groups, other
      determinants presented a varied pattern of risk factors for underutilizing dental
      care. Information on ethnic-specific risk factors can be used to design
      culturally appropriate and acceptable oral health promotion programs.
      Generalizable risk factors across ethnic groups inform oral health policy-makers
      about changing national priorities for promoting oral health.

PMID- 9549992
TI  - Clinical measures and treatment needs.
AB  - Clinically evaluated oral health outcome variables from the ICS-II USA data set
      were examined in the diverse ethnic groups, for two adult age cohorts (35-44 and
      65-74 years). These measures were derived from epidemiological examinations and
      include the DMFT components, loss of attachment, and an indicator of treatment
      need--the ratio of decayed teeth over decayed and filled teeth. The ratio of
      decayed over decayed and filled teeth was used in multivariate analysis, since
      this measure represents an area where public policy could have an impact if
      determinants were understood. The most important independent variables were race
      ethnicity, educational attainment, no fear of dental visits because of pain, and
      oral hygiene practices. Having a usual source of dental care and visiting the
      dentist within the past 12 months did not appear to be as important in predicting
      unmet needs as these other variables. To bridge the gap between the oral health
      status of majority and minority populations, health educators in minority
      communities need to become more accessible, have a pro-active interest in oral
      health, and also be cognizant of the various socio-cultural issues influencing
      oral health. The problems regarding Native American adults are more complex and
      require more careful study.

PMID- 9549993
TI  - Perceived oral health in a diverse sample.
AB  - Measures of perceived oral health represent subjective, individual perspective of
      one's health. One measure commonly used is the single-item perceived oral health
      rating: How would you rate your overall oral health? These analyses examine the
      associations among age, ethnicity, and perceived oral health within the context
      of a comprehensive battery of 21 predisposing, enabling, and need variables. The
      study of compares the adult data from three United States research locations of
      the International Collaborative Study of Oral Health Outcomes (ICS-II). Only
      social survey data were used for this analysis. The multiple regression model
      explains over 30% of the variance in perceived oral health, with R squares
      ranging from 0.324 for Indian Health Service sites to 0.391 for San Antonio. The
      most important significant predictors include ethnic group, education, perceived
      general health status, being edentulous or not having a partial denture, having
      no oral pain, fewer oral symptoms, and having one or more dental visits. The
      predictors of positive perceived oral health for the diverse groups highlight
      interesting age and ethnic differences. The only universal predictor for the
      middle-aged adults was having fewer oral symptoms. For the older adults, being
      edentulous or not having a partial denture was the only universal predictor. The
      findings suggest that perceived oral health may be a useful outcome measure in
      dentistry because of its relation to predisposing sociodemographics and dental
      utilization.

PMID- 9549994
TI  - Consumer satisfaction.
AB  - Patient satisfaction with dental care is compared across six United States
      groups: Whites in Baltimore and San Antonio, African-Americans in Baltimore,
      Hispanics in San Antonio, and Native Americans in the Southwest and the Dakotas.
      First, differences in patient satisfaction across ethnic groups and between two
      age groups (65-74 years old and 35-44 years old) are considered. Generally,
      people from all age and ethnic groups were satisfied with the last dental visit.
      Second, patient satisfaction is conceptualized as an oral health outcome
      influenced by characteristics of the dental service utilizer: predisposing
      sociodemographic characteristics, predisposing oral beliefs, enabling
      characteristics, oral needs, oral health behaviors, and oral health status.
      Multivariate analyses by age and ethnic group are used to identify
      characteristics that influence patient satisfaction. Sociodemographic
      characteristics were important among the elderly. Strong oral health beliefs
      influenced patient satisfaction among younger adults. Enabling characteristics
      were important predictors among the Native American groups. This model explained
      15%-30% of the variability in patient satisfaction among the study age and ethnic
      groups.

PMID- 9549995
TI  - Oral health policy and programmatic implications: lessons from ICS-II.
AB  - The conceptual model used in the ICS-II USA Ethnicity and Aging project helps to
      identify who among the elderly should be targeted for oral health promotion
      initiatives and the kinds of initiatives most likely to promote positive oral
      health outcomes. Outcomes have been measured in this study as perceived by the
      individual and as clinically assessed by the oral epidemiologists. For policy
      purposes, achieving both types of outcomes is important. A typology of oral
      health promotion priorities is used to rank the diverse racial-ethnic groups. In
      the analysis, groups with both low perceived and low evaluated oral health status
      receive highest priority. By these criteria, the older Native American
      populations have the highest priority, followed, in order, by Hispanics, African
      Americans, and non-Hispanic Whites. Policy implications of the empirical analyses
      presented in earlier articles are discussed by use of the conceptual model and
      the typology of oral health promotion priorities. Having a usual source of care
      and/or regular dental visits appears to be a promising avenue for the promotion
      of better-perceived oral health status among most older ethnic groups. Improved
      oral hygiene practices, as represented by both regular toothbrushing and dental
      floss use, promote better clinically evaluated oral health status among many
      older ethnic groups.

PMID- 9549997
TI  - CAD/CAM system to fabricate dental prostheses--CAD for bridge restoration.
AB  - An original CAD process for bridge restoration was developed, and CAD for a
      maxillary left three unit bridge was attempted. The measured shape data of the
      standard crown of a second premolar and molar were deformed, and were applied on
      the dies. The measured pontic data were inserted between two molars. Here, bite
      data of the opposing teeth were introduced, and the occlusal relationship with
      the applied molars was adjusted. The bite data were then replaced by the FGP
      data, and the occlusal surface interference with FGP data was eliminated.
      Connection processes were then carried out. The clearances between the pontic and
      molars were filled with interpolation, and the ends of the applied second molar
      and premolar were connected with the margin of each die. Finally, the data above
      the margin of each die were extracted, and used as the inner crown data for the
      bridge. The whole bridge was designed using a newly developed computer program.

PMID- 9549996
TI  - Effects of various collagen crosslinking techniques on mechanical properties of
      collagen film.
AB  - We examined the relationship between collagen crosslinking techniques and
      dentinum reinforcement. In the present study, the tensile tests, imbibition test
      and antienzyme test were performed on collagen films mainly composed of type I
      collagen after ultraviolet irradiation and immersion in tannic acid and
      glutaraldehyde. The elastic modulus increased with the reaction time, but
      reduction of elongation at breaking point and increased stiffness were observed.
      This tendency was enhanced by ultraviolet irradiation. Tannic acid treatment
      resulted in slower crosslinking than the other two techniques. Antienzyme
      activity was markedly increased by treatment with tannic acid and glutaraldehyde.

PMID- 9549998
TI  - Basic study of a new denture base resin applying hydrophobic methacrylate
      monomer.
AB  - To improve the water sorption of poly(methyl methacrylate), new hydrophobic
      monomers, such as norbonyl and phenyl methacrylate, were studied to determine the
      resin with lower water sorption with no decrease in mechanical property. Water
      sorption of the copolymers of the hydrophobic monomers and MMA decreased with the
      increase in the concentration of the monomers. Compressive and bending strength
      of the copolymers were higher than that of PMMA, and the elastic modulus in
      bending was the same as that of PMMA. In addition, the transverse-deflection
      values satisfied ADA specifications. Dynamic mechanical thermal analysis of the
      copolymers showed a similar tendency to that of PMMA in spite of the introduction
      of bulky groups, such as norbonyl and phenyl, in the polymer molecule. The
      polymerization shrinkage in volume was in the following order: norbonyl < phenyl
      < methyl methacrylate.

PMID- 9549999
TI  - New initiator system for bonding to dentin using methylcyclohexanedione.
AB  - As a part of a series of studies to examine the role of the initiator system in
      dentin bonding, the effectiveness of a new polymerization initiator system
      consisting of 2-methyl-1,3-cyclohexanedione (MCHD) and CuCl2 in dentin bonding
      was investigated in terms of the effects of dentin conditioners and CuCl2
      concentration formulated in MMA/PMMA resins. Curing time and tensile bond
      strength to bovine dentin were measured using resins composed of MMA containing
      0.001-0.03 wt% CuCl2 and PMMA powder containing 2 wt% MCHD. The dentin surfaces
      were treated with six conditioners consisting of 10 wt% phosphoric acid or citric
      acid containing 0-3 wt% FeCl3 or CuCl2. The bond strengths of about 10 MPa
      obtained under optimal conditions were comparable to those reported for
      tributylborane-initiated MMA resin which is one of the most effective bonding
      resins available. Thus, the resin using MCHD/CuCl2 system was concluded to be
      very effective for dentin bonding, especially when dentin was treated with acidic
      conditioners containing ferric or copper chloride.

PMID- 9550000
TI  - Shear bond strengths of a single-step bonding system to enamel and dentin.
AB  - An experimental primer was developed as a single-step bonding system for resin
      modified glass ionomer cements (GIC). Efficacy of this primer on adhesion of
      resin-modified GICs and resin composite to enamel and dentin was evaluated by
      shear bond test and SEM observation. Good bond strengths to enamel were obtained
      (> 11 MPa), whereas significantly low bond strengths to dentin were obtained
      using a single coat of the primer. However, double-coating improved the bond
      strengths to dentin (> 8 MPa). SEM observations indicated that the primer
      functioned as a mild conditioner to remove the smear layer on enamel or dentin
      surfaces. A hybrid layer was observed at the cross-sectional view of the
      GIC/dentin interface. These findings suggested that good adhesion to enamel and
      dentin could be achieved using a single-step bonding system.

PMID- 9550001
TI  - Anisotropic expansion in gypsum-bonded cristobalite investment mold.
AB  - Expansion of a gypsum-bonded investment mold was investigated using a fused
      quartz tube pattern. Two hours after mixing, a fusible alloy was cast into the
      space around the pattern induced by setting expansion. The other molds were
      heated up to 700 degrees C, then a dental silver alloy was cast into the space
      around the pattern induced by total expansion of the mold. Thickness of the
      castings was measured at every thirty degrees on seven cross-sections. The
      setting expansion was almost uniform, but the total expansion was not.
      Especially, a large amount of total expansion was produced toward the open ends
      of the casting ring and toward a seam of the asbestos liner. The thermal
      expansion of the mold was anisotropic because the investment was a mixture of
      calcium sulfate and silica, and was affected considerably by its environment.

PMID- 9550002
TI  - Effect of light wavelength on polymerization of light-cured resins.
AB  - Experimental light-cured composite resins were exposed to a narrow-band light at
      a constant quantum number using a narrow-band interference filter. The IR spectra
      of the cured resin specimens were measured before and after extraction of
      residual monomers. Degree of conversion (DC) and polymerization conversion (PC)
      were calculated from these IR spectra. The light in 410-550 nm could be
      polymerized. With a brief exposure (5 s), DC and PC were affected by the
      wavelength. The effect of wavelength between 410 and 490 nm decreased with
      increasing duration of exposure. The most efficient wavelength was 470 nm and the
      most adequate wavelength was in the 450-490 nm wavelength range. The absorbance
      of camphorquinone strongly affected polymerization, especially during the initial
      stage. However, from the relationship between DC or PC and exposure energy,
      polymerization depended not only on the wavelength of the light, but also on the
      exposure energy.

PMID- 9550003
TI  - Effect of adding ethylene glycol dimethacrylate to resin cements: durability
      against thermal stress of adhesion to titanium.
AB  - The present study was conducted to examine the effect of the addition of a
      dimethacrylate to resin cements on bond strength between titanium and resin after
      thermocycling. Titanium disks, polished and treated with a phosphate monomer,
      were bonded to acrylic rods using two types of experimental resin cements. The
      cements were composed of methyl methacrylate (MMA) containing a tributylborane
      initiator and 0-10 wt% of ethylene glycol dimethacrylate (EGDMA) and two types of
      polymer component of hard poly (MMA) or soft fluoropolymer (2-6F). The bonded
      specimens were subjected to a thermocycling test in water and then to tensile
      strength testing. The addition of 5% or more dimethacrylate monomer to the two
      MMA-based resin cements caused a drastic decrease in bond strength to the metal
      after the thermocycling test. The resin prepared with soft 2-6F as a polymer
      component was significantly more durable than the rigid type resin based on PMMA.
      However, even a 1% addition of ECDMA to the 2-6F resin resulted in a significant
      decrease in durability.

PMID- 9550004
TI  - Thermal diffusivity and specific heat of dental casting alloys at room and
      elevated temperatures.
AB  - Thermal diffusivity and specific heat of four groups of dental casting alloys (Ag
      based, Au-Pd, high karat and Ni-based alloys) were determined. Measurements were
      carried out from room temperature to 750 degrees C in an evacuated electric
      furnace with a laser flash thermal constant analyzer. There was no significant
      difference between the values of thermal diffusivity in the Ag-based and high
      karat alloys; 18-24 and 40-53 mm2/s, at room temperature and at 600 degrees C,
      respectively. For Au-Pd and Ni-based alloys, diffusivity was 8-12 and 3-4 mm2/s
      at room temperature, and 19-22 and 5-6 mm2/s at 600 degrees C, respectively. The
      thermal diffusivity of the alloys was significantly low compared to that of the
      pure-metals of which they were composed. Specific heat was determined as 0.14
      0.16, 0.24-0.34, 0.17-0.19 and 0.45-0.51 kJ/(kg.K) for high karat, Ag-based, Au
      Pd and Ni-based alloys, respectively, at room temperature. Oxidation of the Ni
      based alloy at elevated temperature affected the value of specific heat measured.

PMID- 9550005
TI  - Effect of dimethacrylates in resin cement on durability against thermal stress of
      adhesion to titanium.
AB  - The present study examined the effect of crosslinking of resin cement on
      durability of adhesion between titanium and resin against repeated thermal
      stress. Titanium disks, polished and treated with a phosphate monomer, were
      bonded to acrylic rods with resins composed of poly (methyl methacrylate), methyl
      methacrylate containing 0 approximately 5% dimethacrylates or diacrylate as
      crosslinking agent, and a benzoyl peroxide/amine initiator system. The bonded
      specimens were subjected to thermocycling in water and then tensile strength
      testing. The addition of 5% crosslinking agent, irrespective of its type, to the
      resin resulted in a significant decrease in bond strength after 500 thermocycles.
      No significant difference in durability was revealed among the five crosslinking
      agents studied.

PMID- 9550006
TI  - Titanium in dentistry: development and research in the U.S.A.
AB  - Titanium has received a great deal of attention from dental researchers and
      clinicians. In the United States, the history of the application of titanium as a
      biomaterial started as early as 1940 when experiments with titanium implants were
      done using laboratory animals. It appears that in 1959, two American researchers
      were the first to suggest casting titanium to fabricate implant posts. The use of
      cast titanium for dental prostheses in the U.S. was first reported in 1977. The
      present survey revealed that during the last decade, the number of research
      projects on the applications of titanium to dentistry that were presented at
      annual IADR/AADR meetings has steadily increased. The majority of these
      presentations have been made by American researchers, and 59% of these were
      related to dental implantology. The numbers of reports on casting and
      prosthodontic applications have steadily increased, but they are still more
      limited. The purpose of this review was to provide information on the development
      and the current status of research on titanium in dentistry in the U.S.

PMID- 9550007
TI  - Properties of magnetically attractive experimental resin composites.
AB  - SUS444 stainless steel filled chemically cured resin composites that can attract
      magnet were fabricated. The filler was treated with various concentrations of
      silane. The experimental composite was easy to handle and showed a good shelf
      life. The maximal properties obtained are as follows; The attraction force to a
      magnetic attachment was 1/3-1/4 lower than the commercially available magnet
      keeper system for dental magnetic attachment. Flexural strength and Knoop
      hardness of the composite were 76MPa (7.7 kgf/mm2) and 64 KHN. These values were
      lower than the commercially available chemically cured composite used as a
      reference. Eluted metal from the composite in 1% lactic acid solution for 7 days
      showed 0.7 mg/cm2, but in 0.9% NaCl solution for 7 days, it could not be
      detected.

PMID- 9550008
TI  - Effect of shape and size of silanated fillers on mechanical properties of
      experimental photo cure composite resins.
AB  - The binary system of hybrid fillers selected from four irregular fillers (1.7
      21.5 microns), five spherical fillers (0.46-31.2 microns), and a microfiller of
      0.04 micron, were applied to photo cure composite resin and mechanical properties
      were measured. The strength for the hybrid of irregular and spherical fillers
      tended to increase as the size of component fillers decreased. The strength for
      the hybrid of the same fillers in shape also increased as the size of fillers
      decreased. The strength for the hybrid containing 30% microfiller showed the same
      trend, especially, the largest strength was obtained from hybrids containing
      small spherical fillers.

PMID- 9550009
TI  - Effect of barium in porcelain on bonding strength of titanium-porcelain system.
AB  - The bonding strength to titanium, thermal expansion, and bending strength of
      glassy porcelain containing barium of 5, 10, and 15 mass% were estimated and
      compared with those of barium-free porcelain, to estimate the effect of barium
      content on bonding strength to titanium. The three different glassy porcelains
      containing barium were made by melting at 950 degrees C. The bonding strength of
      a commercial porcelain to titanium increased with the addition of barium. Bending
      strength and thermal expansion were not affected by the barium content.
      Therefore, the addition of barium to porcelain is effective for strengthening the
      bonding of porcelain to titanium.

PMID- 9550010
TI  - Simulation of transient thermal stress in gypsum-bonded investment.
AB  - The aim of this study was to clarify the effect of heating rate on the
      development of both transient and residual stresses in investment molds. Solid,
      cylindrical, gypsum-based molds were modeled and theoretical calculations made of
      temperature distributions with a constant heating rate. These calculations used
      experimental thermal diffusivity data obtained with a laser flash method. The
      simulations calculated transient thermal stresses during heating and at the end
      of heating for two surface conditions: an unrestricted surface, and a surface
      restricted by a casting ring. The simulation model developed nonuniform strains
      and stresses at casting temperature; tangential stress was compressive at the
      surface and tensile at the mid-point for the unrestricted surface model. The
      surface restricted model developed compressive tangential stresses throughout the
      mold at the casting temperature. This resulted in significant thermal strain
      differences compared to the magnitudes of expansion of the mold due to heating.

PMID- 9550011
TI  - Effect of 4-acryloxyethyltrimellitic acid in a self-etching primer on bonding to
      ground dentin.
AB  - To develop a self-etching primer for ground dentin, 4-acryloxyethyltrimellitic
      acid (4-AET) was newly synthesized, and the effect of concentrations varying from
      0 (control) to 56.5 wt% 4-AET in the water/ HEMA primer on bonding to the dentin
      was investigated. Bond strength to the dentin was significantly affected by the
      inclusion of 4-AET in the primer which also contained N,N-di(hydroxyethyl)-p
      toluidine (DEPT) when compared with the control (0% 4-AET) (p < 0.01). The
      optimum 4-AET-concentration and the mean bond strength (SD) were found to be 6.5
      wt%: 24.2 (3.6 MPa, 37.4 wt%: 25.3 (4.4) MPa, 47.2 wt%: 26.9 (11.6) MPa and 54.4
      wt%: 29.7 (12.9) MPa. The role of DEPT in the 4-AET/HEMA primer was assessed, and
      the optimum DEPT-concentration was found to be 0.154 and 0.307 mol%. Regarding
      the hypothetical bonding mechanism to dentin, it was thought that the ionized 4
      AET in water/HEMA would penetrate into dentin substrates, and DEPT as an
      accelerator in situ would facilitate photo-polymerization at the dentin-resin
      interface, and result in increased bond strength to ground dentin.

PMID- 9550012
TI  - Effects of aminobenzoic acid derivatives with 4-AET/HEMA in self-etching primer
      on bonding to ground dentin.
AB  - The effect of the inclusion of aminobenzoic acid derivatives (ABAD) in a self
      etching primer comprising 4-acryloxyethyltrimellitic acid (4-AET), HEMA and water
      on shear bond strength to ground dentin was investigated. The mean bond strengths
      to dentin were significantly increased by the inclusion of 0.307 mol% ABAD in the
      4-AET/HEMA primer, when compared with the control (0 wt% ABAD) (p < 0.01). A
      particularly high value (38.0 MPa) of shear bond strength was obtained in the use
      of the primer containing p-nitroanthranilic acid (p-NAA). It seemed to assume
      that the effect of p-NAA could be caused by the strong electron-withdrawing group
      of -NO2. From SEM observation, it was found that bonding resin appeared to adhere
      strongly to the ground dentin without formation of any resin-tags in the dentinal
      tubules. It was thought that the ABAD with 4-AET/HEMA could perform facilitating
      photo-polymerization at the bonding interface, and resulted in increased bond
      strength to ground dentin, and that the bond strength could be affected by the
      electronegativities of substitutional groups of ABAD.

PMID- 9550013
TI  - Effects of radical polymerizable spirocyclic monomers with new polymerization
      initiator systems on adhesion.
AB  - To develop a non-polymerization shrinkage adhesive resin, the effects of the
      contents varying 0-20 wt% radical polymerizable spirocyclic monomers of 2
      methylene-1, 4, 6-trioxyaspiro [4, 6] undecane (MTSU) and 2-methylene-8, 9-benzo
      1, 4, 6 trioxyaspiro [4, 4] nonane (BTSN) together with three kinds of initiator
      systems in adhesive resin on bonding to both Ni-Cr alloy and unetched enamel were
      investigated. Tensile bond strength to either Ni-Cr alloy or unetched enamel was
      affected by the inclusion of MTSU or BTSN, and indicated that increased contents
      of MTSU or BTSN resulted in decreased bond strength to the metal in the negative
      correlations. Regarding the bond strength to Ni-Cr alloy, however, the effective
      concentration of BTSN was found to be 5 wt%, and the mean bond strength was 58.5
      and 58.6 MPa, respectively. The data of differential scanning calorimeter
      measurement, on the other hand, showed that the copolymerization of MTSU with
      conventional methacrylate monomers was not completely achieved.

PMID- 9550014
TI  - Initial mercury evaporation from amalgams made with in-containing commercial
      alloys.
AB  - This study examined the Hg evaporation behavior during the early setting of
      amalgams that contain In in the alloy powders. Two different types of
      commercially available In-containing alloys were tested: an In-particle admixed
      powder (Indisperse, D) and an In-containing single-composition powder (Indiloy,
      S). Mercury evaporation from specimens (4 mm in dia, 8 mm tall) was monitored 10
      min after trituration to 180 min using a mercury vapor analyzer according to the
      methods used in a previous study. The amounts released from 10 min to 180 min
      were compared with the results of our previous study on a single-composition
      amalgam (Tytin, T) with pure Hg and with Hg-In liquids (5 or 10%). Amalgam S and
      In-containing T terminated Hg evaporation within 180 min. There was no
      significant (p > 0.05) difference in the amount released between T amalgam made
      using pure mercury and D, and between T amalgam made with 5% In-containing
      mercury and S amalgam. Mercury release from amalgam D was significantly (p <
      0.05) higher than from S or both types of In-containing T amalgam. Adding In to
      mercury or alloying In into the alloy particles appeared to be more effective in
      reducing the mercury vapor than admixing pure In particles into the amalgam.

PMID- 9550015
TI  - Adhesion to dentin with resin using sulfinic acid initiator system.
AB  - A study was made on the dentin bonding of MMA/PMMA resin using sulfinic
      acid/BPO/amine polymerization initiator, to examine: 1) the effect of ferric and
      copper chloride contained in phosphoric acid or citric acid dentin conditioners,
      and 2) the effect of the addition of acidic monomers to the resin. Tensile bond
      strength was significantly improved by conditioning dentin with 10% phosphoric
      acid containing 3% ferric chloride. The citric acid-based conditioners and the
      addition of the copper salt to the acidic conditioners were less effective in
      improving bond strength. The mechanism of the improved bond strength is discussed
      in terms of polymerization promoting action of ferric ion at the dentin-resin
      interface. For improving bond strength, the presence of a suitable acidic monomer
      was essential. Its effectiveness depended on the types of acids: Two phosphoric
      acid ester monomers were effective but methacrylic acid had little effect.

PMID- 9550016
TI  - Evaluation of water durability at adhesion interfaces by peeling test of resin
      film.
AB  - The water durability at adhesion interfaces was investigated by measurement of
      the peeled area of thin resin films bonded with 4-META resin on metal surfaces
      after imposing thermal stress using liquid nitrogen. Thermal stress at the
      adhesion interface was calculated by a computer-aided finite element method. On
      18-8 stainless-steel specimens which bond strongly with 4-META resin, total
      interface failure occurs on specimens with resin thicker than 0.55 mm in dry
      condition. A resin layer of 0.25 mm was chosen to study degradation of the
      adhesion interface by water. The shearing stress was calculated as 16 MPa for a
      0.25 mm thick resin layer. On mild-steel adherent interface with 4-META resin
      which degrades rapidly by water molecule, the relationship between water
      immersion time and degradation at the adhesion interface was discussed together
      with the amount of water penetrated at the interface. The method proposed in the
      present study is effective as a quick evaluation method for water durability at
      the adhesion interface.

PMID- 9550018
TI  - Adherence of oral streptococci to composite resin of varying surface roughness.
AB  - The adherence of oral bacteria to composite resins plays an important role in the
      development of secondary caries. The present study deals with the adherence to
      composite resin having various surface roughness of S.oralis, which is frequently
      isolated from composite resin squares attached to maxillary first molars.
      available commercial resin was used in this experiment. In vitro bacterial
      adhesion test was carried out under a sucrose independent conditions. The surface
      roughness values of each specimen ranged between 0.2 micron and 3.0 microns. No
      relationship was observed between the surface roughness values and bacterial
      adhesion because S. oralis adhered firmly to the filler particles of all
      composite resin surfaces.

PMID- 9550017
TI  - Marginal sealability of resin-modified glass ionomers for base/liner: effect of
      hygroscopic expansion and bond strength.
AB  - The present study investigates the effect of storage in water on hygroscopic
      expansion and shear bond strength to dentin at periods up to 1 week, of the resin
      modified glass ionomers for base/liner, and to analyze the effect on the marginal
      gaps in dentin cavities. For polishing after storage in water for 1 day, the
      material indicated significantly smaller marginal gaps both in dentin and in
      Teflon cavities than in those immediately after light-activation. For the results
      of after storage in water for 1 day, the material indicated significantly greater
      bond strength than material immediately after light-activation. The improvement
      of marginal sealability in dentin cavities may be performed not only by
      hygroscopic expansion during storage in water but also by greater bond strength
      after the setting reaction which continues to advance during storage in water.

PMID- 9550019
TI  - Effect of frozen storage and boiling on tensile strength of bovine dentin.
AB  - Bovine teeth are used for dental research as a substitute for human teeth. In the
      present study the effects of storage on the tensile strength of bovine dentin
      were investigated. Storage conditions selected were frozen storage for 1 week, 4
      weeks, and 1 year. Boiling in water for 45 minutes was also employed to clarify
      the effect of heat. Dumbbell-shaped specimens were prepared from teeth of each
      condition and tensile tests were performed immediately. The same tests were also
      performed on specimens, as a control, prepared from bovine teeth within 8 hours
      of extraction. The tensile strength of the control was 76.1 MPa; 1 week frozen
      storage, 78.7 MPa; 4 weeks, 79.9 MPa; 1 year, 79.0 MPa. The tensile strength of
      bovine dentin remained unchanged during one year frozen storage. On the other
      hand, the tensile strength of bovine dentin after boiling was 70.3 MPa, showing
      that tensile strength had decreased.

PMID- 9550020
TI  - Possible segregation caused by centrifugal titanium casting.
AB  - The possibility of the segregation under solidification process using a
      centrifugal casting machine was investigated using an electron probe
      microanalyzer with elemental distribution map, line analysis and quantitative
      analysis. When a very small quantity of platinum was added to local molten
      titanium during the casting process, macroscopic segregation was observed under
      conditions of density difference of 0.1 g/cm3 at the most, confirming that the
      centrifugal force of the casting machine is extremely strong. When a Ti-6Al-4V
      alloy was cast, however, no macroscopic segregation was observed. The centrifugal
      force of the casting machine examined in the present study hardly results in the
      body-force segregation in this titanium alloy.

PMID- 9550021
TI  - Disinfection of removable dentures using ozone.
AB  - Over time, removable dentures tend to become unsanitary and emit unpleasant
      odors, and oral mucosa sometimes becomes inflamed or denture stomatitis is caused
      by denture plaque. Recently, various cleaning products designed to keep removable
      dentures sanitary have appeared on the market. It is known that denture plaque is
      mainly composed of Candida albicans (C. albicans), and that ozone seems to
      inhibit these micro-organisms. Accordingly, a denture cleaner using ozone bubbles
      (ozone concentration of about 10 ppm) was considered as clinically appropriate
      because of its strong disinfecting and deodorizing power, and high biological
      safeness. The effectiveness of this cleaner against C. albicans was investigated
      using. Results showed that C. albicans decreased to about 1/10 after 30 min and
      to 1/10(3) after 60 min.

PMID- 9550022
TI  - Evaluation of skin irritation and sensitization of two diol solutions used as
      experimental dentin primers in humans and guinea pigs.
AB  - The purpose of the present study was to evaluate the safety of ethylene glyco
      (EG) and 1,6-hexanediol (HD) solutions as experimental dentin primers when
      subjected to the guinea pig maximization test (GPMT), primary irritation test,
      cumulative skin irritation test and human patch test. No primary and cumulative
      skin irritation resulting from the use of 62.5% EG or 45% HD solutions was
      observed. In the case of GPMT, the animals sensitized with 2-hydroxyethyl
      methacrylate (2-HEMA) responded to 100% HD. 62.5% EG and 45% HD as dentin primers
      were safer than 2-HEMA such as a methacrylic primer.

PMID- 9550023
TI  - Comparative in vitro investigation of different methods for temporary root canal
      filling with aqueous suspensions of calcium hydroxide.
AB  - Three methods for temporarily filling root canals with calcium hydroxide pastes
      were compared. Each of 20 root canals of extracted, human, single-rooted teeth
      was shaped with hand instruments under standardized conditions up to ISO size 50
      and filled using a syringe system, a lentulo spiral or an endodontic reamer.
      Quality of fillings was assessed radiographically and by inspecting ground
      preparations. Ridit (relative to an identified distribution) analysis was
      employed to confirm differences in frequencies of certain quality criteria
      obtained with various application methods. With regard to degree of obturation
      and occurrence of porosities, application of temporary fillings with a lentulo
      spiral or syringe system revealed significantly better results than application
      with hand instruments (reamer). No differences with regard to degree of
      obturation were detected when comparing results obtained with syringe or lentulo.
      Fewer porosities in the apical part of the root canal were seen, both on
      radiographs and ground sections, with the syringe system compared with the
      lentulo spiral. In the presence of some contradictory reports found in the
      literature, the present study suggests that, after straight or slightly curved
      root canals have been shaped up to at least ISO size 50, high quality temporary
      root canal fillings may be obtained by application of an aqueous suspension of
      calcium hydroxide with a syringe system.

PMID- 9550024
TI  - Periodontal healing of extracted dogs' teeth air-dried for extended periods and
      soaked in various media.
AB  - The aim of this study was to determine the periodontal healing of replanted dogs'
      teeth which, after extended extra-oral dry times, had been soaked in various
      media before replantation. Incisors and premolars of beagle dogs were root canal
      treated, extracted and bench dried. The teeth were grouped according to dry times
      of 30, 45 and 60 minutes. Each group of teeth was soaked in one of three media,
      Hank's balanced salt solution, ViaSpan (Belzer UW-CSS, Dupont Pharmaceuticals),
      or Conditioned Medium (supernatant of confluent culture of human gingival
      fibroblasts) for 30 minutes before replantation. Controls consisted of teeth
      extracted and replanted without drying on soaking (negative control), and bench
      dried teeth replanted without soaking in the media (positive control). The dogs
      were killed 6 months after replantation of the teeth, which were prepared for
      histologic evaluation. Five microns cross-sections (every 70 microns) of the root
      and surrounding tissue were evaluated for healing/resorption according to
      Andreasen's criteria. The best healing occurred for the roots which had been
      immediately replanted. Healing in the positive control groups decreased with
      increased dry time. For the 30-minute dry time groups, soaking in media had no
      beneficial effect on periodontal healing compared with the controls. Soaking in
      ViaSpan resulted in an increased healing incidence for both the 45- and 60-minute
      bench-dried groups while soaking in the other media had no consistent beneficial
      effect. It appears from this study that an avulsed tooth that has been left dry
      for 30 minutes should be replanted immediately without soaking. However, teeth
      that have been dry for 45 or 60 minutes would benefit from soaking for 30 minutes
      in ViaSpan.

PMID- 9550025
TI  - Hydroxyl radical activity in thermo-catalytically bleached root-filled teeth.
AB  - Intra-coronal bleaching of root-filled teeth has been associated with invasive
      cervical root resorption. It is considered that during bleaching hydrogen
      peroxide diffuses through the tooth structure into the cervical periodontium,
      resulting in periodontal tissue destruction and initiating a resorptive process.
      Hydrogen peroxide is capable of generating hydroxyl radical, an oxygen-derived
      free radical, in the presence of ferrous salts. Hydroxyl radicals are extremely
      reactive and have been shown to degrade components of connective tissue,
      particularly collagen and hyaluronic acid. The aim of the present study was to
      determine whether hydroxyl radicals are generated during the bleaching of root
      filled teeth which have been discoloured by blood. Forty extracted human premolar
      teeth were root-filled with gutta-percha and AH26 sealer cement. Twenty of the
      teeth were experimentally discoloured by blood. All teeth were then thermo
      catalytically bleached using 30% hydrogen peroxide while tooth roots were seated
      in a test solution of sodium salicylate. Hydroxyl radical generation was
      determined by the detection of reaction products of this radical with salicylate
      using high performance liquid chromatography with electrochemical detection (HPLC
      ECD). The presence of hydroxyl radicals was detected in twenty-five of the teeth.
      There was a significant association between the production of hydroxyl radicals
      and the presence of tooth discolouration caused by blood components. Greatest
      yields of hydroxyl radicals occurred in teeth in which EDTA had been used to
      clean the pulp chamber prior to bleaching. It was concluded that hydroxyl
      radicals are generated during the thermo-catalytic bleaching of root-filled
      teeth. Generation of this toxic chemical species may be one mechanism underlying
      periodontal tissue destruction and root resorption after intra-coronal bleaching.

PMID- 9550026
TI  - Electrical impedance measurements of root canal length.
AB  - Electronic methods are now widely used during endodontic treatment for the
      assessment of root canal length. These commonly measure the electrical resistance
      or impedance between the root canal and the buccal mucosa. A number of studies
      have been undertaken to determine the accuracy of commercially available
      instruments. The aims of this investigation were to determine the electrical
      impedance characteristics of the root canal and periapical tissues in vivo,
      measure the changes relative to the distance of an endodontic instrument from the
      apical constriction and propose an equivalent circuit modelling the periapical
      tissues. The length of the root canals of 20 previously untreated teeth were
      determined using radiographic and electronic methods. Minimal canal preparation
      was carried out and measurements were made with a size 10 K-Flex file. A
      microprocessor-controlled LCR analyser was used to measure the electrical
      impedance characteristics of each root canal. The instrument measured the series
      and parallel resistive (RS, RP) and capacitance (CS, CP) component of the tissues
      at two test frequencies, 100 Hz and 1 kHz. Measurements were made for each root
      canal when the diagnostic file was placed at the apical constriction and repeated
      when the file was withdrawn to -0.5, -1.0, -1.5, -2.0 and -5.0 mm from the
      foramen. Readings were taken for each canal after the canal had been dried with
      paper points, and flooded first with deionised water and then with sodium
      hypochlorite. The root canals were then prepared, cleaned and obturated using
      standard endodontic procedures. The LCR analyser selected the series resistance
      component as the major measurement parameter. There was a clear increase in
      series resistance (RS) with increasing distance from the radiographic apex for
      dry canals and those containing deionised water and sodium hypochlorite. The mean
      resistance for dry canals was markedly higher than for those containing fluid,
      ranging from 22.19 k omega to 92.07 k omega in comparison with 9.32 k omega to
      12.10 k omega for deionised water and from 7.46 k omega to 8.92 k omega for
      canals containing sodium hypochlorite. There was a marked change in the series
      and parallel resistive component with distance from the apex, suggesting a
      complex relationship between the impedance of the smear layer and bulk dentine.
      The impedance characteristics of a root canal were a complex electrical network
      comprising resistive and capacitive series and parallel elements.

PMID- 9550028
TI  - Effect of laser treatment on the root canal of human teeth.
AB  - The purpose of this study was to examine the morphological and temperature
      changes of the apical portion of human extracted teeth treated by Nd: YAG, CO2
      and Argon-lasers. Seventy-two single-rooted human teeth were studied. The root
      canals were prepared conventionally. Laser treatment of the apical portion of the
      canal was carried out by means of an optic fiber or metal tip. Temperatures were
      recorded thermographically. Two-thirds of the specimens were stained with black
      India ink and 36% silver ammonium fluoride solution. All specimens were
      irradiated by the three types of lasers at several intensities and the
      temperatures were recorded. Half of the specimens were prepared for the
      telescopic light microscope and for scanning electron microscopic observation,
      and the rest for histopathological examination by light microscope. The scanning
      electron microscopic evaluation showed that the laser energy vaporized the
      deposited debris, producing a glaze-like surface. The histopathological
      investigation revealed a tapered, enlarged apical lased area. All three laser
      devices were capable of vaporizing the debris in this way but the degree of
      morphological change was highly dependent on energy level and duration. The Argon
      laser produced the highest temperatures.

PMID- 9550027
TI  - Tooth discoloration by blood: an in vitro histochemical study.
AB  - An in vitro model, using a modification of a technique devised by Freccia &
      Peters, was developed to investigate tooth staining following pulpal haemorrhage.
      Samples of whole blood, erythrocytes, plasma and platelet concentrate and saline
      were individually placed in the pulp chambers of groups of five teeth and
      centrifuged twice daily for 25 min over a period of 3 consecutive days. This
      confirmed that the blood pigment responsible for the staining was found only in
      those samples containing erythrocytes. Teeth stained with packed red cells were
      then prepared for histological examination and subjected to four histochemical
      tests: (1) benzidine, (2) zinc leuco, (3) Perl's and (4) Turnbull Blue to analyse
      some of the biochemical changes following haemorrhage into the pulp chamber.
      These tests showed that, following haemolysis of erythrocytes within dentine,
      haemoglobin was found either intact or as one of the haematin molecules with no
      further breakdown of the haem structure and no evidence of any free ferric ions
      or haemosiderin.

PMID- 9550029
TI  - A case of severe vestibular root angulation.
AB  - In this article, we describe the appearance and management of an impacted
      permanent tooth with severe vestibular root angulation. In addition, the possible
      origin of this type of root malformation as well as some of their epidemiologic
      aspects are discussed.

PMID- 9550030
TI  - Endodontic therapy for a fused mandibular molar.
AB  - Variations in tooth morphology present a clinical challenge when endodontic
      treatment is required. A case of conservative endodontic therapy for a fused
      mandibular second and third molar is presented.

PMID- 9550031
TI  - Root canal instruments for manual use: a review.
AB  - Root canal instruments can be subdivided into instruments made of different
      alloys (stainless steel, nickel-titanium and nickel-aluminium) and instruments
      with different geometric forms (e.g., instruments with short cutting segments).
      Several types of stainless steel and titanium-based instruments are presented and
      assessed by a review of the current literature. In summary, flexible stainless
      steel instruments with noncutting tips seem to be a decisive improvement in the
      development of an ideal root canal instrument. They are superior to titanium
      based instruments in both cutting efficiency and instrumentation of curved root
      canals.

PMID- 9550032
TI  - A comparison of dentine removal using safety or conventional Hedstrom files.
AB  - Mandibular molars (n = 20) were divided and the mesial roots mounted in an
      acrylic mould which allowed them to be removed, sectioned horizontally and then
      reassembled. The furcal root canal wall thickness 7 mm from the apex was measured
      prior to instrumentation. The roots were allocated to two groups (n = 10). One
      group was instrumented using the step back technique with safety Hedstroms in one
      canal and conventional Hedstrom files in the other canal. The second group was
      instrumented using a crown down approach (using files and Gates Glidden drills to
      provide early radicular access). The furcal root canal wall thickness was then
      remeasured and the amount of dentine removed calculated. The results showed that
      the safety Hedstrom file removed less dentine from the furcal region of the canal
      compared to the conventional Hedstrom file. This however was not statistically
      significant (Paired t test, n = 10, p > 0.05). The amount of dentine removed
      using the crown down technique was significantly greater than that using the step
      back technique (Two sample t, n = 20, p < 0.01). In conclusion, less dentine was
      removed from the furcal region with safety Hedstrom files compared to
      conventional Hedstrom files; however, Gates Glidden drills removed more dentine
      than either type of hard file.

PMID- 9550033
TI  - Periapical status, quality of root canal fillings and estimated endodontic
      treatment needs in an urban German population.
AB  - The objective of this study was to determine the periapical status and the
      quality of root canal fillings and to estimate the endodontic treatment needs in
      a German population. Clinical and radiographic data and the operative procedures
      performed were evaluated on 323 patients coming to a dental surgery in Stuttgart,
      Germany, in 1993. In 182 individuals at least one tooth exhibited a root canal
      filling, a necrotic pulp or an irreversible pulpitis. Out of the 7897 teeth
      examined, 215 (2.7%) had a root canal treatment (category A), 122 being non
      endodontically treated (1.5%) did not respond to the sensitivity test (category
      B) and 53 (0.7%) were diagnosed as having irreversible inflamed pulp tissue
      (category C). The prevalence of teeth associated with radiographic signs of
      periapical pathosis was 61% in the group of root canal filled teeth and 88% in
      the group of pulpless and non-endodontically treated teeth. Using the level and
      the density of the root canal filling as criteria for evaluating the technical
      standard, only 14% of the endodontic treatments of non-apicectomized teeth were
      qualified as adequate. The minimal endodontic treatment need is 2.3% related to
      all examined teeth when the root canal filled teeth with clinical symptoms of
      periapical periodontitis (category A) and those of categories B and C are
      included. The real endodontic treatment need is suggested to be larger when
      considering that the technical quality of the obturation is poor in most
      symptomless endodontically treated teeth associated with a periapical lesion. In
      the case of retreatment of these teeth, the endodontic treatment need would then
      be calculated at 3.7%.

PMID- 9550034
TI  - Prognosis of permanent teeth with internal resorption: a clinical review.
AB  - This study was performed in order to report the clinical features of internal
      resorption cases and evaluate their prognosis after endodontic treatment. Twenty
      seven patients with 28 teeth with internal resorption were referred to our clinic
      and 20 teeth were treated endodontically. Sixteen teeth had non-perforating
      internal resorption and were treated by conventional root canal therapy. The
      remaining 4 teeth had perforating internal resorption and were initially treated
      by remineralization therapy with calcium hydroxide. The teeth treated by
      conventional root canal therapy showed clinical and radiographic evidence of
      healing. However, the remineralization therapy was successful in only one case.
      The three failed cases were subsequently treated by endodontic surgery. The
      surgical therapy was unsuccessful in one case due to extensive loss of marginal
      alveolar bone and increased tooth mobility.

PMID- 9550035
TI  - Coronal leakage in teeth root-filled with gutta-percha and two different sealers
      after long-term storage.
AB  - This in vitro study investigated the effect of long-term storage on the coronal
      leakage of a microbial marker in teeth root-filled with lateral condensation of
      cold gutta-percha and one of two sealers. Sixty single-rooted teeth were prepared
      chemomechanically to a size 40 master apical file. The teeth were divided into
      two groups of 20 teeth each and obturated with gutta-percha using either Apexit
      or Tubliseal EWT sealer. The teeth were stored for 6 months in artificial saliva
      and tested for leakage using a marker consisting of Anaerobic streptococci and
      Prevotella intermedia. The teeth were checked for bacterial leakage daily for 90
      days. All positive control teeth leaked within 48 hours, while the negative
      control teeth remained uncontaminated throughout the test period. Leakage in the
      experimental teeth started at times varying from 10 to 71 days; 30% and 75% of
      the specimens of the Apexit and Tubliseal EWT groups respectively showed leakage
      at 90 days. The Tubliseal EWT group showed significantly more leakage (p < 0.05)
      than the Apexit group.

PMID- 9550036
TI  - Possible application of transmitted laser light for the assessment of human
      pulpal vitality.
AB  - The purpose of this study was to determine whether use of transmitted laser light
      would enable a better assessment of human pulpal vitality than back-scattered
      light does (LDF: laser Doppler flowmetry). The experiments were carried out on
      ten upper central incisors in six subjects aged 23-28 years; five of the teeth
      were vital with no restoration, and five were non-vital. For use with transmitted
      laser light, the fibers within the probe of a conventional LDF apparatus were
      used, one for transmitting light onto the buccal surface, the other for receiving
      it at the palatal surface of the same tooth. For LDF, the probe was fixed at the
      buccal surface. Blood flow was measured at three different locations on each
      experimental tooth: the incisal third, the center and the cervical third of the
      tooth crown. In non-vital teeth, 1) output signals with transmitted laser light
      all registered zero, and no oscillation could be seen in recordings from any
      location on the tooth, but 2) LDF signals were above zero, there were regular
      oscillations related to heart rate, and passive increases in blood flow
      (corresponding to blood pressure increases) were recorded from both the center
      and the cervical third of the tooth, indicating that LDF registered blood flow of
      non-pulpal origin. In vital teeth, LDF signals were significantly higher than in
      non-vital teeth at each location on the tooth. At the central site on vital
      teeth, the output signals for transmitted laser light were about twice those seen
      with LDF, and passive blood flow changes corresponding to blood pressure
      increases were more clearly observed. These results indicated that transmitted
      laser light would be useful for the assessment of tooth pulp vitality both
      because the blood flow signals did not include flow of non-pulpal origin, and
      because its output signals and response to blood flow changes were clear and
      could easily be monitored.

PMID- 9550037
TI  - Intra-alveolar surgical uprighting of impacted teeth: a case report.
AB  - Although orthodontic repositioning of impacted teeth is widely used, the
      treatment has its limitations. Autotransplantation or intra-alveolar surgical
      repositioning of teeth is an alternative therapy that may be used in selected
      cases of desperate impactions, when orthodontic extrusion is unsuccessful or when
      orthodontic treatment is rejected by the patient. A case report is presented to
      stress both the indications and limitations of a modified technique of intra
      alveolar surgical uprighting of impacted teeth.

PMID- 9550038
TI  - Endodontic treatment of an unusual mandibular second molar.
AB  - A case involving unusual pulpal morphology due to fusion or gemination was
      treated by conservative endodontic treatment. Clinically, the involved mandibular
      second molar had an enlarged clinical crown and an extra cusp with a deep carious
      lesion. Careful negotiation, instrumentation and obturation of the root canal
      system led to successful treatment.

PMID- 9550039
TI  - Concomitant intrusive luxation and root fracture of a central incisor--report of
      a case.
AB  - A case of a 9-year-old boy who presented with intruded maxillary central
      incisors, one of which had also sustained a middle third root fracture, is
      reported. The root fracture was diagnosed after orthodontic extrusion was
      started, which resulted in separation of the apical and coronal fragments. The
      hypermobile coronal fragment was stabilised by passing a K file through a palatal
      access cavity into the root canal of the apical fragment. Orthodontic alignment
      was completed and the fractured incisors were restored with the file left in
      situ. At a 10-year follow-up, the incisors were clinically healthy and continued
      to satisfy aesthetic and functional demands.

PMID- 9550040
TI  - Avulsed permanent teeth: a review of the literature and treatment guidelines.
AB  - Dental trauma represents one of the few situations where dentists are called upon
      to make unscheduled diagnostic and treatment decisions in an area that is outside
      their routine experience. Since patients who sustain an avulsion present
      infrequently, except in child-oriented or emergency-based practices, clinicians
      often make diagnostic and management decisions based upon their previous rare
      treatment experiences. Clinicians also rely on published guidelines for this
      aspect of their practice and expect these standards to be up-to-date and based on
      current research information. None of the current protocols has been tested by a
      prospective longitudinal outcome study in humans. Nevertheless, current
      guidelines have become the standard for clinical practice around the world. An
      effort must be made to develop treatment protocols that are based upon the
      biological mechanisms that underlie periodontal wound healing.

PMID- 9550041
TI  - An evaluation of after-office-hour dental trauma in Singapore.
AB  - The purpose of this study was to assess the post-traumatic sequelae and treatment
      outcome and the corresponding prognostic factors at the initial emergency visit.
      Over a 5-year period, the authors collected case records from 129 dental trauma
      patients. These patients had been referred subsequent to receiving emergency
      treatment after office hours at the Accident and Emergency Department of
      Singapore General Hospital. After the exclusion of 31 cases with concomitant
      fracture of maxilla and/or mandible and cases with insufficient documentation,
      the final study sample consisted of 98 patients (41 males, 57 females) who had
      sustained injuries to 264 permanent teeth. The main cause of dental trauma was
      falls (56%), and the main type of injuries was periodontal tissue injuries with
      or without concomitant injuries to hard tissue, including root fracture (73%).
      For the final evaluation, teeth with insufficient recall period were excluded
      before univariate and multivariate stepwise logistic regression analysis. It was
      found that for 100 teeth with luxation type of injuries, the presence of
      concomitant hard tissue injuries retained prognostic significance for pulpal
      outcome (p < 0.001) after adjusting for severity of luxation, while the severity
      of luxation was the only significant factor for periodontal outcome (p < 0.001).
      For 34 avulsed teeth, the stage of root development was the major factor
      associated with the pulpal outcome (p = 0.003), while extra-alveolar storage
      media were found to be significantly related to the periodontal outcome (p <
      0.001). For 72 teeth with hard tissue injuries, first-visit interval played a
      significant role in the outcome (p = 0.03). Although the sample size in the root
      fracture group was too small for such statistical analysis, the results indicated
      that patient education on dental trauma was an important factor. Thorough
      standardized documentation was also recommended to facilitate optimal follow-up
      management and future research as well as medico-legal purposes.

PMID- 9550043
TI  - Radiological assessment of the effects of potential root-end filling materials on
      healing after endodontic surgery.
AB  - The effects of three root-end filling materials on healing following endodontic
      surgery were assessed radiologically and correlated with histological findings
      reported elsewhere. The materials compared were a light-cured glass ionomer
      cement (Vitrebond), a reinforced zinc oxide-eugenol cement (Kalzinol) and
      amalgam. The root canals of 27 two-rooted mandibular premolar teeth of six beagle
      dogs were inoculated with endodontic pathogenic bacteria to induce periradicular
      lesions. The roots were apicected and root-end cavities filled with the tested
      filling materials. The teeth and surrounding jaw were removed after 4 weeks (30
      roots) or 8 weeks (24 roots). Radiographs were taken of each jaw section and
      subjected to image analysis. Healing was evaluated based on measurements of the
      size of the periradicular radiolucent areas. ANOVA disclosed no statistically
      significant differences in the size of the periradicular areas either between
      time periods or between materials. These results did not correlate with the
      tissue responses in the same material as assessed histologically and previously
      reported. The use of radiographs alone to assess healing after endodontic surgery
      in the dog mandible is unsatisfactory, and should not be regarded as a substitute
      for histological examination for the determination of healing.

PMID- 9550042
TI  - The role of the socket in the periodontal healing of replanted dogs' teeth stored
      in ViaSpan for extended periods.
AB  - In a previous study on the extended storage of extracted dogs' teeth, it was
      hypothesized that changes in the socket environment might play a role in the
      periodontal healing of these teeth. The purpose of this study was to evaluate the
      role of the socket in the periodontal healing of replanted dogs' teeth. Extracted
      endodontically treated dogs' teeth were stored in ViaSpan for 6 hours and
      replanted into sockets after 6, 48 or 96 hours. Controls included teeth extracted
      and replanted immediately, 48-hour stored teeth replanted into 48-hour sockets
      and 96-hour stored teeth replanted into 96-hour sockets. After 6 months the dogs
      were killed and the teeth prepared for histologic evaluation according to
      Andreasen. Overall healing for the groups and healing for teeth within the groups
      were evaluated and compared. The best results were obtained when the teeth were
      replanted immediately. For the teeth stored in ViaSpan for 6 hours, complete
      healing decreased significantly as the age of the socket increased. In addition,
      the rate of replacement resorption increased significantly with increasing socket
      age for the 6-hour stored teeth. Forty-eight-hour stored teeth replanted into 48
      hour sockets had the lowest healing rate with levels of inflammatory resorption
      not seen in the other groups. According to the results of this study, the socket
      environment plays an important role in the healing of replanted teeth in dogs.

PMID- 9550044
TI  - Accuracy of apex locator.
AB  - An evaluation of the accuracy of the "Root ZX" apex locator was conducted on 20
      single-rooted teeth that had been extracted because of severe disease or
      orthodontic treatment. After the pulp chamber had been accessed and the tooth
      length determined using the Root ZX apparatus, the file was fixed to the tooth
      with light-cured composite resin. After extraction, the tooth was longitudinally
      ground with a diamond bur until the file was visible. The distance between the
      file tip and the apical foramen was measured under a microscope (x 100). The
      results showed that the tip of the instrument reached the apical foramen in all
      teeth.

PMID- 9550045
TI  - Direct digital radiography for the detection of periapical bone lesions: a
      clinical study.
AB  - The aim was to compare the observer performance of direct digital radiography,
      with and without image processing, with that of conventional radiography, for the
      detection of periapical bone lesions. For 50 patients, a conventional periapical
      radiograph using E-speed film was taken. Then, a direct digital image of the same
      area was made. The images presenting the periapical bone tissue of 59 roots were
      assessed by seven observers using a 5-point confidence scale. The digital images
      were first presented as original images, with default contrast and brightness set
      by the computer system. Following this, the observers were allowed to use the
      processing facilities for greyscale treatment. The results for original and
      processed direct digital images and for conventional radiographs were compared by
      Receiver Operating Characteristic (ROC) analysis. The area under the ROC curve,
      calculated as P(A) value, was 0.88 for conventional film, 0.82 for original
      digital images and 0.78 for processed images. Corresponding Az values were
      slightly higher, 0.89, 0.84 and 0.81. Statistically significant differences
      between ROC areas calculated as P(A) values for the methods were found.
      Comparison between Az values showed no significant differences between
      conventional radiographs and original digital images, whereas the difference
      between Az values for original and processed digital images was still
      significant. It was concluded that conventional film radiography performed
      slightly better for the detection of periapical bone lesions than direct digital
      radiography and that image processing did not improve the observer performance.

PMID- 9550046
TI  - Long-term follow-up of conservative treatment of severely traumatized maxillary
      incisors.
AB  - We present the case of a 26-year-old man who at the age of 9 suffered severe
      trauma to both maxillary central incisors. The underlying malocclusion was
      skeletal and classified as dental Class II/1 with severe crowding. Both the
      maxillary central incisors and the two lower first premolars were extracted and
      the patient was treated with an edgewise appliance for 2 years. Acceptable
      occlusal relationships were achieved following orthodontic and adjunctive
      treatment which consisted of reshaping the maxillary lateral incisors with
      composite materials and grinding the canines to resemble lateral incisors. A
      critical evaluation of the esthetic and functional results at the age of 26 years
      is presented.

PMID- 9550047
TI  - Crown-root fracture of lower molar--restorative procedures.
AB  - Endodontically treated teeth may undergo crown, crown-root, or root fractures.
      The treatment of fractured teeth can be complicated, sometimes because of
      difficulties with the final restoration. This case report describes a case of
      crown-root fracture of a left lower first molar in which endodontic treatment and
      rapid orthodontic eruption of the tooth made a good prosthetic restoration
      possible.

PMID- 9550048
TI  - Multiple dens invaginatus affecting maxillary lateral incisors and a
      supernumerary tooth.
AB  - Dens invaginatus is a developmental variation resulting from an alteration in the
      normal growth pattern of the dental papilla of a tooth. This anomaly occurs
      predominantly in maxillary permanent lateral incisors. Multiple occurrence in
      maxillary incisor teeth in the same patient has frequently been reported, and
      examination of bilateral teeth for the anomaly is often carried out routinely.
      This paper reports an unusual case of multiple invaginations, including dens
      invaginatus affecting maxillary lateral incisors and a supernumerary tooth and
      minor invaginations of the upper canines. Moreover, the case illustrates the
      importance of examining all the teeth in patients who present with dens
      invaginatus and palatal pits in incisors and canines. The possibility that the
      supernumerary tooth had resulted from gemination of the lateral incisor tooth
      germ is discussed.

PMID- 9550049
TI  - Endodontic hand instruments: cutting efficiency, instrumentation of curved
      canals, bending and torsional properties.
AB  - In an assessment of the usefulness of different root canal instruments, two
      aspects are of particular interest for the endodontist: the cutting efficiency of
      the instruments and their ability to enlarge curved canals without undesirable
      changes of the canal shape such as the formation of zips and elbows. This review
      paper is based on own investigations on the cutting efficiency and
      instrumentation of curved canals. Additionally, two parameters which are
      described in ISO 3630-1, resistance to bending and resistance to fracture, are
      discussed. With regard to cutting efficiency in rotary motion, flexible stainless
      steel reamers and K-files clearly display the best results and are superior to
      conventional stainless steel as well as titanium-based reamers and K-files.
      Regarding cutting efficiency in linear motion, stainless steel Hedstrom files
      made by certain manufacturers are significantly superior to stainless steel and
      titanium-based Hedstrom files of other brands. Flexible stainless steel
      instruments with modified noncutting tips clearly produce the best canal shape in
      curved canals. With only rare exceptions, all the instruments tested fulfilled
      the requirements of the ISO standard concerning resistance to fracture and
      resistance to bending.

PMID- 9550050
TI  - A histological and quantitative histomorphometric study of apexification of
      nonvital permanent incisors of vervet monkeys after repeated root filling with a
      calcium hydroxide paste.
AB  - The purpose of this study was to compare the effect of a monthly refilling of the
      root canals with calcium hydroxide paste with a single packing or replacement of
      the paste at 3 months on the apexification of nonvital maxillary incisors of
      vervet monkeys. Forty-eight maxillary incisors from 12 monkeys were used
      following radiographic determination that root development was incomplete. The
      pulps were extirpated under general anesthesia and the root canals filed and
      cleaned. The root canals were filled with a commercial calcium hydroxide paste,
      Calxyl, and a temporary cavity filling placed. Twelve teeth were left without
      further treatment. The calcium hydroxide paste was replaced in 12 teeth after a 3
      month interval, and in the remaining 24 teeth the calcium hydroxide root filling
      was replaced five times at monthly intervals. The monkeys were killed after 6
      months, and blocks of the teeth and surrounding tissues were embedded,
      decalcified and 6 microns serial sections prepared and stained. The sections were
      studied histologically to evaluate 11 parameters. Significant differences were
      found in the amount of calcium hydroxide at the apices, the presence of new
      cementum on the roots and the degree of inflammation, all of which were better in
      the monthly refill group. Histomorphometric measurements to evaluate the
      obturation of the open apices and the volume of new primary osteocementum showed
      no significant difference between the three groups. It was suggested that after
      the initial root filling with calcium hydroxide there was nothing to be gained by
      repeated root filling either monthly or after 3 months, for at least 6 months.

PMID- 9550051
TI  - Computerized 3-D reconstruction of two "double teeth".
AB  - "Double teeth" is a root malformation in the dentition and the purpose of this
      study was to reconstruct three-dimensionally the external and internal morphology
      of two "double teeth". The first set of "double teeth" was formed by the
      conjunction of a mandibular molar and a premolar, and the second by a conjunction
      of a maxillary molar and a supernumerary tooth. The process of 3-D reconstruction
      included serial cross-sectioning, photographs of the sections, digitization of
      the photographs, extraction of the boundaries of interest for each section,
      surface representation using triangulation and, finally, surface rendering using
      photorealistic effects. The resulting three-dimensional representations of the
      two teeth helped us visualize their external and internal anatomy. The results
      showed: a) in the first case, fusion of the radical and coronal dentin, as well
      as fusion of the pulp chambers; and b) in the second case, fusion only of the
      radical dentin and the pulp chambers.

PMID- 9550052
TI  - Tritiated thymidine uptake in periodontal ligament cells of dogs' teeth stored in
      various media for extended time periods.
AB  - The purpose of this study was to evaluate a new storage solution, Conditioned
      Medium, vs Hank's balanced salt solution and ViaSpan with respect to the
      viability of periodontal ligament cells of exarticulated teeth. Teeth were stored
      for periods of 6, 48, and 96 hours in Hank's balanced salt solution, ViaSpan
      (Dupont Pharmaceuticals), or Conditioned Medium. Teeth were cultured for 24 hours
      in Dulbecco's medium supplemented with tritiated thymidine. The cultured teeth
      were sectioned and evaluated with autoradiography. Control teeth were extracted
      and immediately treated as above without storage. Mitotic activity was indicated
      by clusters of five or more grains over the nuclei of fibroblasts in the
      remaining periodontal membrane. The ratio of labeled to unlabeled cells (labeling
      index) was calculated for each treatment group. When storage time was compared
      across all groups, 96 hours was significantly different from 6 and 48 hours (P <
      0.001 and P < 0.012 respectively). Storage time of 6 hours was not significantly
      different from 48 hours (P > 0.10). After comparison of the nine experimental
      groups with the control group, only Hank's balanced salt solution at 96 hours was
      significantly different (P < 0.004).

PMID- 9550053
TI  - Cutting pattern of Flexogate instruments in plastic blocks.
AB  - Design modifications of endodontic instruments have been made to improve
      instrumentation in curved root canals. A new instrument, the Flexogate
      (Maillefer), has been introduced to overcome some of the problems associated with
      preparation of the apical part of the root canal. The purpose of this study was
      to investigate the cutting pattern of Flexogates in curved canals (45 degrees) in
      clear plastic blocks, prepared by four different operators. Image analysis was
      used to take accurate measurements of canal shape before and after
      instrumentation to calculate cutting patterns. The results showed that Flexogates
      did not remain centred in the canal of a plastic block during cutting; maximum
      transportation occurred in the apical third of the outer curve, with little or
      none in the middle and coronal thirds. The clinical implications of this study
      require further investigation of the effect of coronal preflaring, and
      experimentation in teeth.

PMID- 9550054
TI  - Effect of XeCl-308nm excimer laser on the mineral content of human dentin.
AB  - The effect of the XeCl-308nm excimer laser on the mineral content and surface
      morphology of cut dentin was examined in ten extracted human teeth. Each dentin
      specimen was lased for 4 s at a fluence of 1 J/cm2 and a frequency of 25 Hz. Non
      lased area of the same specimen served as control. Scanning electron microscopy
      and energy dispersive spectrometry revealed a significant decrease in the
      phosphorus levels following laser treatment. A decrease in calcium levels also
      occurred but was not statistically significant. Nonsignificant changes in sulphur
      and potassium levels were also noted. Morphologically, the lased dentin showed an
      apparently melted surface with partial obstruction of the dentin tubules as well
      as cracks along the lased surface. Therefore, it appeared that laser treatment
      may alter the chemical structure as well as the surface morphology of the dentin.

PMID- 9550055
TI  - Urinary catecholamine levels and dentofacial injuries in children.
AB  - This study investigated the relationship between urinary catecholamine levels and
      dentofacial injuries in 221 children, boys and girls, aged 8 to 10 years.
      Dentofacial injuries were recorded by a questionnaire and a clinical examination.
      Three 24-h urine samples, taken with an interval of 1 year between each, were
      available for each subject. A representative urine sample from each examination
      was analyzed by the high-performance liquid chromatography technique to assay the
      catecholamine content. Socioeconomic factors were recorded by a questionnaire. Of
      the examined children 58 (24 boys and 34 girls) with complete 24-h urine samples
      showed neither historical nor clinical evidence of dentofacial injuries and
      constituted the control group. Two case groups, A and B, with historical and/or
      clinical evidence of dentofacial injuries were matched by age and gender.
      Differences in the quantitative and qualitative data were tested by the paired t
      test and the chi 2 test, respectively, while a regression analysis was applied to
      measure the effects of norepinephrine on epinephrine and dopamine. The 95%
      probability level was used. The results showed significant differences between
      control and case group A in the epinephrine and norepinephrine levels of the
      second urine sample. Significant differences were also found between control and
      case group B at the first urine sample in epinephrine and dopamine and at the
      second in epinephrine. Injured boys had significantly higher values of all
      catecholamines except for epinephrine in the second urine sample than injured
      girls. The only significant difference found between boys and girls without
      dentofacial injuries was in norepinephrine in the second urine sample. The data
      suggested that children with dentofacial injuries are more frequently under
      emotional stress and consequently emotionally stressful children run a greater
      risk of sustaining such injuries.

PMID- 9550056
TI  - Toothache with a multifactorial etiology: a case report.
AB  - A case report of orofacial pain originating from both dental and nondental
      conditions is presented. The spontaneous throbbing pain initiated from the left
      maxillary second premolar and spread throughout the entire upper part of the face
      to the frontoparietal area. Root canal treatment of the maxillary second premolar
      did not resolve the chief complaint. Magnetic resonance imaging examination
      revealed hypertrophy of the left inferior turbinate and soft tissue haziness in
      the left maxillary sinus floor. After antrostomy, submucosal turbinectomy, and
      endodontic treatment, the patient was free from pain. The final diagnosis of this
      case, in addition to pulpitis, was maxillary sinusitis with chronic rhinitis. The
      multiple factors associated with the etiology made the diagnosis difficult. The
      mechanism of referred pain from the maxillary sinus and paranasal mucosa to the
      maxillary teeth and face is discussed.

PMID- 9550058
TI  - Provisionalization for ceramic laminate veneer restorations: a clinical update.
AB  - At the inception of ceramic veneer restorations in the early 1980s, provisional
      veneer restorations were not customarily placed over teeth which had undergone
      tooth reduction. During the last several years, provisional veneer restorations
      have been utilized with increased frequency for a variety of valid reasons. The
      learning objective of this article is to examine the reasons for the increased
      utilization of provisional veneer restorations and to describe a selection of the
      clinical methods employed for direct and indirect fabrication. The indications
      and contraindications for provisionalization are presented. Four case reports are
      utilized to describe and illustrate the various clinical circumstances, the
      provisionalization procedures, the appropriate instruments, and the materials
      that facilitate the fabrication of aesthetic, functionally sound, and
      biocompatible provisional restorations.

PMID- 9550057
TI  - Treatment of a horizontal root fracture by vital root submergence.
AB  - Cervical third horizontal root fractures in immature permanent teeth often
      present complicated and unpredictable treatment options. This case report
      describes the successful management of a horizontal root fracture in an open apex
      tooth by vital root submergence and subsequent nonsurgical root canal therapy.

PMID- 9550059
TI  - Bone rehabilitation to achieve optimal aesthetics.
AB  - Treatment involving oral implants has established a high success rate, including
      implant survival on a long-term basis. The challenge facing the clinicians today
      is to achieve an optimal long-term aesthetic result. To address this challenge,
      the volume of the underlying hard and soft tissue must be restored either prior
      to or simultaneously with the implant placement. The learning objective of this
      article is to review the critical biologic and clinical criteria essential in
      achieving a predictable success in aesthetic enhancement of the implant site. The
      article discusses the five phases of ridge reconstruction, utilization of bone
      grafts (with or without membranes), and the use of membranes alone. Soft tissue
      management and augmentation in aesthetic and nonaesthetic regions are
      differentiated and presented. Surgical complications are recognized as a clinical
      reality, and exposure of the membranes is evaluated and discussed. Four cases are
      used to describe and illustrate the clinical procedure.

PMID- 9550060
TI  - The aesthetic composite anterior single crown restoration.
AB  - Achieving natural aesthetics by harmoniously matching the shape and color of a
      single anterior crown is perhaps one of the greatest challenges in restorative
      dentistry. The clinician must often rely on the artistic skills of a laboratory
      technician who has no direct access to the patient. The shade selection process
      is, therefore, impaired, and the final result may be a restoration which does not
      emulate the aesthetics of the adjacent natural dentition. The learning objective
      of this article is to present an innovative technique which utilizes the
      qualities of high strength laboratory processing in association with the
      application of light curing and freehand bonding of composite resins. This
      combination allows the clinician to predictably achieve aesthetic results with
      single anterior crowns. The direct, indirect, and indirect/direct restorations
      are discussed, and the laboratory and clinical procedures are reviewed.

PMID- 9550062
TI  - Winning with goals.

PMID- 9550061
TI  - The aesthetic composite bridge.
AB  - New developments are constantly introduced in the search for the optimal
      treatment modality to restore a single anterior tooth. The patient attention has
      shifted to aesthetics of the restoration, biocompatibility of the dental
      materials utilized, conservative preparation of the teeth to be restored, and the
      retention of intact adjacent dentition. The learning objective of this article is
      to review the methods currently utilized and to present a recently introduced
      treatment modality--the two-component bridge, which combines the strength and
      resiliency of composite resin with the aesthetic advantages of porcelain. The
      technology of the material is reviewed, the predominantly lingual tooth
      preparation procedures are outlined, and the bridge try-in is described. The
      advantages of the two-component bridge are presented along with the
      contraindications and suggestions of careful case selection. Three cases with
      congenitally missing maxillary lateral incisors in youthful patients are
      presented to supplement the theoretical outline and to describe and illustrate
      the clinical procedure.

PMID- 9550063
TI  - Sphenopalatine ganglion neuralgia.

PMID- 9550064
TI  - Electronic dental anesthesia: an injection-free alternative--a review.

PMID- 9550065
TI  - Considerations for the aesthetic restoration of endodontically treated anterior
      teeth following intracoronal bleaching.
AB  - The major considerations in restoring the pulp chamber following bleaching of
      endodontically treated anterior teeth include aesthetics, function, appropriate
      endodontic access preparation, amount of remaining tooth structure, type of
      restorative material, prevention of microleakage, and prevention of iatrogenic
      perforation. The learning objective of this article is to review the
      considerations that must be made when placing aesthetic restorations in the pulp
      chamber and access opening of endodontically treated teeth following intracoronal
      bleaching. The advantages and disadvantages of the proposed techniques and
      materials are discussed, as are the methods for avoiding excessive removal of the
      tooth structure. Two case reports are used to demonstrate the clinical
      procedures. The authors suggest placing white gutta-percha stopping material in
      the pulp chamber and a composite restoration in the access opening following root
      canal treatment and/or bleaching procedures in the anterior dentition.

PMID- 9550066
TI  - Megabrasion: a conservative strategy for the anterior dentition.
AB  - Continuous developments in adhesive restorative techniques, tooth whitening
      procedures, and restorative materials have significantly broadened the initially
      defined spectrum of indications for composite restorations. These developments
      have thereby contributed to the achievement of one of the major objectives of
      conservative restorative dentistry--the maximum preservation of sound tooth
      structure. In order to optimize the application of modern composite resin
      technology, mastering the basic principles of natural aesthetics is an essential
      prerequisite. The learning objective of this article is to discuss the etiology
      of enamel discoloration and conservative treatment strategies, including
      microabrasion and masking procedures. Emphasis is placed on a simple procedure-
      the megabrasion technique--which does not depend extensively on the artistic
      skills of the operator. It represents a useful and predictable approach for the
      elimination of white opaque stains on the enamel and yellow-brown enamel
      discolorations.

PMID- 9550067
TI  - Generational differences in implant prosthodontics: a biomechanical solution.
AB  - Correct placement of implants is facilitated by the parameters that are already
      established, dictated by the struts and borders of the existing implant frame.
      The root-form implants should be: Contained in the anterior symphysis of the
      mandible. Completely encompassed in bone, without any contact with the Vitallium
      frame. As long as possible, to enhance biomechanical support of the superimposed
      bar and prosthesis. Evenly dispersed, in order to support a Hader bar.
      Independent of the previous implant system. Placed to fill the anteroposterior
      spread as completely as possible. The rationale and approach should comprise
      these requirements in order to achieve a predictable solution to mechanical
      failure of a subperiosteal implant, in an efficient manner, with the least
      possible trauma to the patient.

PMID- 9550068
TI  - Conservative direct and indirect resin posterior restorative alternatives for
      cracked dentition.
AB  - Cracked posterior teeth are often discovered when an existing restoration is
      removed for routine treatment. When the entire cusp is completely worn or
      fractured, recent advances in dentin bonding technology, ceramic systems, and
      composite restorative materials allow conservative onlay restorations as opposed
      to the aggressive removal of sound tooth structure for a full-coverage crown
      restoration. Questions have arisen as to what is the optimal treatment when
      cracks are discovered in posterior dentition when the cusps remain intact, i.e.,
      whether the unaffected cusps should be removed. The learning objective of this
      article is to present conservative alternatives to the aggressive removal of
      sound tooth structure, utilizing direct resin restorative materials and current
      adhesive technology.

PMID- 9550069
TI  - Effects of dental trauma on the pulp.
AB  - Infection of the root canal system following dental trauma induces pulp and
      periapical disease and prevents healing of previously healthy pulp. A clinical
      goal in treating trauma is the maintenance of pulp vitality, and clinicians
      should be aware of factors that influence pulp healing. The learning objective of
      this article is to review the factors and techniques that influence pulp vitality
      and examine the influence pulp has on the healing of adjacent tissues. The
      potential routes for bacterial infection of the root canal system are discussed,
      with the clinical crown as the primary portal of entry. Uncomplicated and
      complicated crown fractures, as well as the crown-root and root fractures, are
      reviewed. Complications in pulp healing include canal obliteration, disturbed
      root development, apexogenesis, apexification, and the various forms of
      resorption.

PMID- 9550070
TI  - Restoring Class V lesions Part I: Carious lesions.

PMID- 9550071
TI  - Pain management. Choices.

PMID- 9550072
TI  - Replacement of missing mandibular lateral incisors with a single pontic all
      ceramic prosthesis: a case report.
AB  - The conventional approach for replacing congenitally missing mandibular lateral
      incisors dictates the placement of either a conventional porcelain-fused-to-metal
      (PFM) bridge, Maryland bridge, or fiber-reinforced composite veneer bridge.
      However, several appearance-related disadvantages have been reported in the use
      of a prosthesis which incorporates a metal substructure. To address these
      limitations, metal-free restorative alternatives have been recently developed to
      expand the clinical options when fabrication of these prostheses is indicated.
      The learning objective of this article is to present the utilization of a single
      pontic all-ceramic resin-bonded bridge to replace congenitally missing mandibular
      lateral incisors, where the existing mesiodistal spaces were narrow and the
      abutment teeth exhibited insufficient substance for the conventional treatment
      modality.

PMID- 9550073
TI  - An orally administered drug for treatment of periodontal disease.

PMID- 9550074
TI  - Dentoalveolar morphology: evaluation of natural root form versus cylindrical
      implant fixtures.
AB  - The function of implant-supported restorations is now routinely achieved. As a
      result, the emphasis in restorative implant dentistry has shifted from function
      to aesthetics and the biocompatibility of the materials utilized. The learning
      objective of this article is to review the three major components essential to
      achieving natural aesthetics in implant-supported restorations--hard tissue
      dynamics, soft tissue dynamics, and dental aesthetics. Particular emphasis is
      directed to the dentoalveolar anatomy and morphology. Analysis of the tooth root
      morphology and dimensions has resulted in the design and fabrication of
      restorative components with dimensions that closely resemble the natural tooth
      anatomy and aesthetics. A system of transmucosal abutments has been designed, and
      its utilization is presented in this review.

PMID- 9550075
TI  - Clinical analysis and treatment of spaced dentition.
AB  - Spaced dentition is a common clinical finding, caused by a variety of factors. In
      each case, careful analysis of clinical symptoms is mandatory for effective
      treatment planning. Care should be taken to apply the least complicated treatment
      plan for obtaining the most successful result. Spaced dentition often exists in
      the presence of otherwise intact teeth; therefore, special care should be taken
      in order to prevent overtreatment. Surgical fibrotomies, complex orthodontic
      treatment, and prosthetic solutions that require sacrifice of sound tissue are
      often unnecessary. This article describes a case of large maxillary and
      mandibular midline diastemata, controlled by a combination of orthodontic therapy
      with porcelain laminate veneer restorations. The learning objective of this
      article is to develop a rational approach to spaced dentition analysis that leads
      to the most appropriate treatment plan for each individual case.

PMID- 9550076
TI  - Restoring Class V lesions Part 2: Abfraction lesions.

PMID- 9550077
TI  - Dramatic misalignment of maxillary anterior teeth and generalized destruction of
      bone and periodontal tissue.

PMID- 9550079
TI  - Periodontics: past and present.

PMID- 9550078
TI  - Post and core reconstruction for fixed prosthodontic restoration.
AB  - If the previous restorative therapy or dental caries has resulted in substantial
      loss of tooth structure, the abutment teeth for fixed prosthodontic restorations
      require a core reconstruction or a post and core. Small dentin defects can be
      restored with bonded cores; more extensive dentin defects that are often
      accompanied by previous endodontic treatment generally require additional support
      for the core material. A direct procedure with a bonded post is a viable
      treatment method. The decision to use either light-conducting all-ceramic
      zirconium or titanium as a post material depends on the aesthetic requirements
      present. The indications for a cast post and core as an indirect procedure for
      prosthodontic reconstructions appear to be decreasing. The learning objective of
      this article is to review the past and current post and core materials and
      techniques. Indications for core reconstruction with vital teeth and posts and
      cores for pulpless teeth are discussed.

PMID- 9550080
TI  - Operative dentistry: the missing clinical standards.
AB  - Since the development of advanced adhesive technology, the use of amalgam has
      declined significantly. The search for amalgam substitutes, i.e., restorative
      materials which maintain similar clinical function and cost-effectiveness as
      amalgam, has so far been unsuccessful. It has also become evident that a
      considerable confusion prevails regarding the objectives of restorative
      procedures. In absence of national and international standards, the products--the
      restorations--are assessed according to varied criteria. In placing restorations,
      three objectives are attained, at most: a) tooth preservation, b) tooth
      preservation and function, and c) tooth preservation, function, and imperceptible
      restitution. The learning objective of this article is to discuss the positive
      effects that could be attained by defining the standards, terminology, and the
      quality assessment criteria for operative dentistry in regard to the patients and
      the dental profession.

PMID- 9550081
TI  - Sometimes, it's all in the timing!

PMID- 9550083
TI  - TMJ injuries from direct trauma.

PMID- 9550082
TI  - The effect of core translucency on the aesthetics of all-ceramic restorations.
AB  - Recent advances in ceramic technology have revolutionized aesthetic dentistry.
      When treating a single anterior tooth in need of a full-coverage restoration, a
      multitude of options in restorative materials and techniques is available to the
      clinician. The learning objective of this article is to present and evaluate a
      selection of all-ceramic dental materials currently available for aesthetic full
      coverage crown restorations. When selecting an all-ceramic system, there are
      several major factors to consider, including the inherent translucency of the
      ceramic material and of the adjacent dentition, the color of the prepared tooth,
      and the forces anticipated in that region. Preparation and restoration of
      discolored and nondiscolored tooth structure are reviewed. The techniques
      presented can be utilized to obtain predictable results in the anterior region
      for aesthetic all-ceramic full-coverage restorations.

PMID- 9550084
TI  - Dens invaginatus--a pathway to pulpal pathology: a literature review.
AB  - Dens invaginatus is the most common dental anomaly in a group of dental
      anomalies, related by their embryologic development and by the fact that their
      defects provide a potential pathway for bacteria to cause pulpal pathology. It
      occurs when the inner enamel epithelium invaginates into the dental papilla prior
      to calcification. It exists in erupted teeth as an enamel-lined tract, which
      either ends in a blind sac inside the crown or root or exits into the periodontal
      ligament. The lining may be incomplete in areas and may not protect the pulp.
      Methods of providing preventive treatment for teeth with dens invaginatus are
      described. When pulpal pathosis occurs, the dens may displace the pulp and
      complicate access cavity preparation and subsequent endodontic treatment,
      adversely affecting the prognosis. The learning objective of this article is to
      present treatment planning considerations and suggestions.

PMID- 9550085
TI  - A study of baker's yeast reduction of piperidone-carboxylates.
AB  - The stereoselective baker's yeast reduction of various N-protected piperidone
      carboxylic acids have been studied, and the enantioselectivity was found to be
      widely dependent on whether fermenting or non-fermenting conditions were
      employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic
      acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert
      butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however,
      with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave
      7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert
      butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting
      baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic
      acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for
      determining the enantiomeric excess of the hydroxypiperidine carboxylic acids
      derivatives was found in the reaction with Sanger's reagent followed by HPLC on a
      chiral column.

PMID- 9550086
TI  - Synthesis of substituted chiral piperazones resembling aza-sugars.
AB  - (6R)-6-(Hydroxymethyl)piperazin-2-one (1), (6S)-6-(hydroxymethyl)piperazin-2-one
      (2) and (6S)-6-[(1R, 2S, 3R)-1,2,3,4-tetrahydroxybutyl]piperazin-2-one (3) have
      been prepared in optically pure forms starting from D-glucosamine hydrochloride
      (4). The compounds (1-3) were tested for glycosidase inhibition.

PMID- 9550087
TI  - Synthesis of meiosis-activating sterols containing fluorine.
AB  - It is documented that specific types of sterol play a major role in the
      resumption of meiosis in oocytes from mice in vitro. 4,4-Dimethyl-5 alpha
      cholesta-8,14,24-trien-3 beta-ol (FF-MAS) isolated from human follicular fluid
      and 4,4-dimethyl-5 alpha-cholesta-8,24-dien-3 beta-ol (T-MAS) isolated from bull
      testicular tissue, have been shown to activate (promote) meiosis in vitro. In
      order to evaluate the biological activity and stability of such compounds, new
      demethylsterol derivatives have been synthesised. Using diethylaminosulfur
      trifluoride (DAST) it was possible to synthesise selected delta 8, delta 14
      sterols with mono and difluoro substitution at C3.

PMID- 9550088
TI  - 1-Thiopsoralen, a new photobiologically active heteropsoralen. Photophysical,
      photochemical and computer aided studies.
AB  - 1-Thiopsoralen (7H-thieno[3,2-g]benzofuran-7-one) 1, a lead compound of a series
      of heteropsoralens, was investigated. The electronic transitions involved were
      studied. Fluorescence quantum yield is very low, while laser flash photolysis
      showed that the triplet state is practically the sole transient of 1.
      Fluorescence quantum yield (phi F) and triplet lifetime (tau F) as well as
      triplet quantum yield (phi T) and lifetime (tau T) were determined. The
      production of singlet oxygen was also evaluated by photophysical measurements.
      Photophysical data suggest that DNA photobinding of 1, owing to short
      fluorescence lifetime value and high triplet quantum yield, occurs likely through
      triplet mechanism. Interactions between 1 and DNA were studied both in the ground
      and the excited state. In the ground state 1 undergoes intercalation inside
      duplex DNA. This fact is also supported by molecular modeling studies. By UVA
      light activation 1 photobinds covalently to DNA forming mono and diadducts. The
      furan side 1-thymine monoadduct, isolated from DNA photomodified by thiopsoralen,
      shows a cis-syn stereochemistry, in agreement with quantum mechanics studies.
      Compound 1 photobinds also with linolenic acid, component of lecithins, giving a
      C4-cycloaddition, and supporting that this compound also induces photolesions at
      the level of cell membrane, like psoralen. Compound 1 exhibits strong skin
      phototoxicity.

PMID- 9550089
TI  - Photoreaction of furocoumarins with DNA is similarly inhibited by minor and major
      groove-interacting ligands.
AB  - It was found that methyl green, a major groove binding ligand and the minor
      groove binding ligands, netropsin and 2,7-di-tert-butylproflavine inhibit, to a
      similar extend a monoadduct forming benzopsoralen and monoadduct and diadduct
      forming derivatives of psoralen (8-methoxypsoralen and 3,4'-dimethyl-8
      methoxypsoralen). Caffeine exhibits an inhibitory effect on furocoumarin
      photobinding to DNA at 10(3) fold higher concentration. Together with the
      previously published results it is concluded that both occupancy of the major and
      minor groove as well as intercalation hinder photobinding of furocoumarins to
      DNA.

PMID- 9550090
TI  - Transformation of some pyrido[2,3-d]pyrimidine derivatives into other di- and
      triheterocyclic systems.
AB  - It was stated that three analogous ethyl 2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3
      d]pyrimidine-5-carboxylates (7-9) react with hydrazine hydrate giving derivatives
      of the new heterocyclic system pyrido[2,3,4-ef]pyridazino[3,4-e]-1,2,4-triazepine
      (10-12), pyrido[3,4-d]pyridazine (16-18) and pentaazaphenalene (13-15). The
      latters were formed in low yields. The results of the preliminary pharmacological
      study of 2 of these compounds are reported.

PMID- 9550091
TI  - One-step synthesis and pharmacological activity of new (N-substituted)amino
      spiroalkan-dione derivatives.
AB  - The synthesis of (N-substituted)amino-spiroalkan-dione derivatives 3 is described
      starting from enamines 1 and carbon suboxide 2, and their inhibitory effects on
      blood coagulation in vivo and on platelet aggregation in vitro are determined.
      Some of synthesized compounds showed a strong anticoagulant activity. A
      comparative pharmacological study of the anticoagulant effects of the new
      compounds versus Warfarin suggests that their behaviour is analogous, though the
      action mechanism is different.

PMID- 9550092
TI  - Glycosidopyrroles. Part 2. Acyclic derivatives: 1-(1,3-dihydroxy-2
      propoxy)methylpyrroles as potential antiviral agents.
AB  - The series of 1-(1,3-dihydroxy-2-propoxy)methylpyrroles 2a-o were prepared in
      good overall yields according to Scheme I. When evaluated for antiviral activity
      against HIV-1, only compounds of the triphenyl series (R3 = NH2, N3, Br) were
      found to inhibit the HIV-1 replication at concentrations that were very not
      cytotoxic for MT-4 cells, with selectivity index 1.5-9.3. None of these compounds
      showed antibacterial or antifungal activity.

PMID- 9550093
TI  - Anti-HIV agents. V. Synthesis, structure and in vitro anti-HIV activity of novel
      1H,3H-naphtho[2',3':4,5]imidazo[1,2-c]thiazoles.
AB  - A series of 1H,3H-naphtho[2',3':4,5]imidazo[1,2-c]thiazoles, TBZ analogues, was
      prepared in order to explore the influence on anti-HIV activity of the spatial
      requirements of the hydrophobic moiety fused to imidazothiazole system. In spite
      of a butterfly-like conformation evidenced by X-ray analysis of compound 4g, the
      results of in vitro screening suggest that the replacement of the benzene fused
      ring by the naphthyl moiety negatively influences the activity of analogous
      thiazolobenzimidazole derivatives, some of which are potent non-nucleoside HIV-1
      RT inhibitors.

PMID- 9550094
TI  - Synthesis and antimicrobial activity of some new derivatives of 6,12
      dihydroindolo[2,1-b]quinazolin-6,12-dione.
AB  - Some derivatives of tryptantrine were prepared in order either to increase
      solubility and to study structure-activity relationship. All synthesized
      compounds were tested for antimicrobial activity.

PMID- 9550095
TI  - Synthesis and microbiological activity of some novel N-(2-hydroxyl-5
      substitutedphenyl)benzacetamides, phenoxyacetamides and thiophenoxyacetamides as
      the possible metabolites of antimicrobial active benzoxazoles.
AB  - Synthesis of some novel N-(2-hydroxyl-5-substitutedphenyl)benzacetamides,
      phenoxyacetamides and thiophenoxyacetamides (5a-k) were described in order to
      determine their in vitro antimicrobial activity against 3 Gram-positive, 3 Gram
      negative bacteria and the fungus Candida albicans comparing with several control
      drugs. The derivative 5e was found active at a MIC value of 25 micrograms/ml
      against the whole tested Gram-positive bacteria strains and the Gram-negative
      microorganism Klebsiella pneumoniae. Moreover, the synthesized compounds 5a-k
      exhibited significant antibacterial activity against the enterobacter Pseudomonas
      aureginosae when compared to the control drugs. For the antifungal avtivity
      against C. albicans, the compound 5k was found more active than the other
      synthesized derivatives. On the other hand, the antimicrobial activity of some of
      these acetamide derivatives (5c, 5d, 5e, 5j and 5k) which are the possible
      metabolites of benzoxazoles, were also compared with their cyclic analogues 6-10.
      However, most of the MIC values of the benzoxazole derivatives provided better
      activity than the compared acetamides, while some others of the acetamide
      derivatives possessed either one fold improved (5d, 5e and 5j) or the same
      potency (5c, 5d, 5e, 5j and 5k) against the tested microorganisms.

PMID- 9550096
TI  - Evaluation of antimycobacterial and anticonvulsant activities of new 1-(4
      fluorobenzoyl)-4-substituted-thiosemicarbazide and 5-(4-fluorophenyl)-4
      substituted-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives.
AB  - Some new 1-(4-fluorobenzoyl)-4-alkyl/arylthiosemicarbazide (2a-g), 5-(4
      fluorophenyl)4-alkyl/aryl-2,4-dihydr-3H-1,2,4-triazole-3-thio ne (3a-g)
      derivatives, 3-(benzylthio)-5-(4-fluorophenyl)-4-phenyl-4H-1,2,4-triazole (3h)
      and 2-acetyl-5-(4-fluorophenyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thi one
      (3i) were prepared and tested for their antimycobacterial and anticonvulsant
      activities. The structure of compounds was confirmed by elemental analyses and
      spectroscopic techniques. The antimycobacterial activity of the synthesized
      compounds was investigated against M. fortiutum ATCC 6841 and most of them were
      found active against the above strain with MIC values of 64 or 32 micrograms/ml.
      The anticonvulsant activity of the 2d, 3d-i was determined against
      pentylenetetrazole induced seizures. 3f-i showed anticonvulsant activity (10 to
      30% protection).

PMID- 9550097
TI  - Bioabsorbable polyphosphazene matrices as systems for calcitonin controlled
      release.
AB  - To provide a suitable delivery system for the calcitonin controlled release 80 mg
      bioabsorbable polyphosphazene matrices were obtained with entrapped 50 or 250
      micrograms calcitonin. The in vitro behaviour demonstrated a release burst for
      about 24 hours, followed by a period of slow release of the peptide lasting for
      weeks. Matrices containing 250 micrograms calcitonin were implanted under general
      anaesthesia in osteoporotic female rats, while a group of animals (control group)
      received unloaded matrices. After thirty days a second batch of matrices was
      implanted in both groups to prolong the period of treatment until two months. The
      explanted matrices were histologically evaluated together with the surrounding
      tissues, and the dosage of the residual calcitonin was also performed. Results
      demonstrated the good biocompatibility of the system and the complete release of
      the calcitonin from the matrices 30 days after implantation. The therapeutic
      effect, after sixty days of treatment was confirmed by the better densitometric
      values observed in the femoral bone of treated animals than in controls.

PMID- 9550098
TI  - Effects of a benzimidazole compound on monooxygenase activities.
AB  - A retinoid-type benzimidazole compound (benzimidazole-tetranaphthalene, BITN) was
      synthesized and its effects on hepatic cytochrome P450 (CYP) dependent
      ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD)
      enzyme activities were determined in rats in vitro. In vitro addition of BITN in
      10(-3) M concentration to the reaction medium caused inhibitions in EROD (94%)
      and PROD (82%) activities. With the same concentration (10(-3) M) all-trans
      retinoic acid (RA) was able to inhibit EROD activity 65% and PROD activity 59%
      whereas buthylated hydroxytoluen (BHT) inhibited EROD and PROD activities 73% and
      62%, respectively. The specific inhibitors of EROD activity (caffeine) and PROD
      activity (SKF 525A) at 10(-3) M concentration inhibited the corresponding enzymes
      33% and 77%, respectively. Thus, these results reveal that the BITN has a
      stronger inhibitory effect than RA, BHT, caffeine and SKF 525 A on the enzyme
      activities. Since these enzymes (EROD, CYP 1A1/2 and PROD, CYP2B1) activate
      polycyclic hydrocarbons, aromatic amines and aliphatic halogenated hydrocarbons
      to their ultimate mutagenic or carcinogenic forms, and are effective in producing
      reactive oxygen species such as superoxide, hydroxyl radical and hydrogen
      peroxide, the new compound, BITN, appears to have a greater anticarcinogenic and
      antioxidant potential than RA and BHT.

PMID- 9550099
TI  - Synthesis, lipophilicity and biological properties of some novel 1H-1,2,4
      triazole derivatives.
AB  - A series of new 1H-1,2,4-triazole derivatives was synthesized and evaluated as
      potential antiviral (i.e. anti-influenza virus), antibacterial and antifungal
      agents. The lipophilicity of the compounds was also investigated using
      calculation procedures. Among the test compounds none showed specific activity
      against influenza virus, although compound 3a, the most hydrophilic member of the
      series, showed weak activity against Bacillus subtillis.

PMID- 9550100
TI  - Maintaining fixed band spacing when changing column dimensions in gradient
      elution.
AB  - In gradient elution separations, it may be required to change either column
      length (to increase resolution or shorten run time) or column diameter (for an
      increase in sensitivity or for preparative separations). In either of these
      changes of column dimensions, it is usually desired to maintain the same relative
      band spacing (selectivity), so as to increase resolution in proportion to (column
      plate number)1/2 when increasing column length, or to maintain constant
      resolution when changing column diameter. A general rule for avoiding changes in
      band spacing in these situations is to maintain the quantity [(gradient time) x
      (flow-rate)/(column volume)] constant, while holding the initial and final
      gradient mobile phase compositions (%B) fixed. This rule is only valid as long as
      the equipment hold-up volume (dwell volume) is negligible, or if all sample
      components are strongly retained at the start of the gradient. When neither of
      the latter conditions apply, then significant changes in band spacing may result
      when changing column size. Rules are presented for recognizing this potential
      problem for a given sample/HPLC-equipment combination, and adjustments in
      separation conditions that can avoid this problem are discussed. Changes in band
      spacing as a result of change in column size are of special concern when
      developing procedures for preparative chromatography under gradient conditions.

PMID- 9550101
TI  - Dye-ligand and metal chelate poly(2-hydroxyethylmethacrylate) membranes for
      affinity separation of proteins.
AB  - Cibacron Blue F3GA was covalently immobilized onto poly(2-hydroxyethyl
      methacrylate) pHEMA) membranes via the nucleophilic reaction between the chloride
      of its triazine ring and the hydroxyl group of pHEMA. Then, Fe3+ ions were
      complexed by chelation with the immobilized Cibacron Blue F3GA molecules.
      Different amounts of Fe3+ ions were loaded on the membranes by changing the
      concentration of Fe3+ ions and pH of the reaction medium. Membranes with or
      without Fe3+ were used in the adsorption of glucose oxidase, catalase and bovine
      serum albumin. The adsorption capacities of these membranes were determined by
      changing pH and the concentration of the proteins in the adsorption medium. The
      adsorption phenomena appeared to follow a typical Langmuir isotherm. The maximum
      capacities (qm) of the Fe3+ complexed membranes for glucose oxidase, catalase and
      bovine serum albumin (8.70 x 10(-3) mumol m-2, 2.15 x 10(-3) mumol m-2 and 2.21 x
      10(-3) mumol m-2) were greater than those of the untreated membranes (6.79 x 10(
      3) mumol m-2, 1.34 x 10(-3) mumol m-2 and 1.94 x 10(-3) mumol m-2) respectively.
      The nonspecific adsorption of the enzymes and the protein on the pHEMA membranes
      was negligible.

PMID- 9550102
TI  - Trace determination of methanol in water-ethanol solution by derivatization and
      high-performance liquid chromatography.
AB  - A simple and sensitive high-performance liquid chromatographic method has been
      established for the determination of methanol in water-ethanol solution. The
      method is based on the transfer of the methoxide anion, which is formed from
      methanol under strong alkaline treatment in aqueous solution, by benzalkonium
      chloride into the dichloromethane organic phase for derivatization with 3
      bromomethyl-7-methoxy-1,4-benzoxazin-2-one. The derivative obtained was separated
      on a LiChrospher diol column with n-hexane-dichloromethane (9:1, v/v) as the
      mobile phase. Several parameters affecting the partition/derivatization of
      methanol were investigated. The linear range for the determination of methanol
      was 2-20 mumol/ml; the detection limit (signal-to-noise ratio = 5; sample size,
      10 microliters) of methanol was about 0.10 mumol/ml (R.S.D. = 16%, n = 3). The
      method has been satisfactorily applied to the assay of methanol in spiked
      commercial liquors.

PMID- 9550103
TI  - Quantitative analysis of flavonols, flavones, and flavanones in fruits,
      vegetables and beverages by high-performance liquid chromatography with photo
      diode array and mass spectrometric detection.
AB  - A high-performance liquid chromatographic (HPLC) separation method with photo
      diode array (PDA) and mass spectrometric (MS) detection was developed to
      determine and quantify flavonols, flavones, and flavanones in fruits, vegetables
      and beverages. The compounds were analysed as aglycones, obtained after acid
      hydrolysis of freeze-dried food material. Identification was based on retention
      time, UV and mass spectra by comparison with commercial standards, and the UV
      peak areas were used for quantitation of the flavonoid contents. Examples of HPLC
      MS, analyses of orange pulp, tomato, and apple are presented. The method has been
      used to screen foods on the Danish market, and the contents of flavones,
      flavonols, and flavanones were measured.

PMID- 9550104
TI  - Separation of indenestrol A and B isomers and enantiomers by high-performance
      liquid chromatography.
AB  - High-performance liquid chromatography (HPLC) methods have been developed for the
      separation of substituted indenestrol A and B isomers on different columns. The
      isomers were separated by normal-phase liquid chromatography with a silica gel
      column. Enantiomers of these compounds were separated by chiral HPLC and the most
      successful separations were achieved with a Chiralcel OJ column.

PMID- 9550105
TI  - Zn(2+)-selective purification of recombinant proteins from the milk of transgenic
      animals.
AB  - The milk of transgenic livestock is becoming a viable, large-scale source of post
      translationally complex, recombinant therapeutic proteins. Recombinant vitamin K
      dependent proteins such as human protein C (rhPC) and Factor IX can be produced
      in milk. However, rate limitations in post-translational modification such as
      intrachain proteolytic cleavage and gamma-carboxylation occur in the mammary
      gland. Thus, most desirable recombinant products often exist as sub-populations
      in milk because the mammary gland tends to secrete incompletely processed
      polypeptides. In general, a nonaffinity purification strategy by which to purify
      mature recombinant proteins from milk is desirable. Zn2+ is used to selectively
      modify ion-exchange adsorption behavior of endogenous and recombinant milk
      proteins through conformational changes which cause aggregation and or
      precipitation. Zn(2+)-selective precipitation of milk and recombinant proteins
      results in the purification of active rhPC at high yield from the milk of
      transgenic pigs using expanded bed chromatography. This method selects for rhPC
      which is both heterodimeric and properly gamma-carboxylated. Due to the homology
      of milk proteins among different species, this same Zn(2+)-selective
      precipitation strategy is useful for developing purification methods for other
      recombinant proteins from the milk of transgenic livestock.

PMID- 9550106
TI  - Affinity chromatography of thiol ester-containing proteins.
AB  - A method is described for the affinity chromatographic purification of thiol
      ester proteins. These comprise the complement proteins C3 and C4 and the protease
      inhibitor alpha 2-macroglobulin (alpha 2M) and are known to contain an internal
      beta-cysteinyl-gamma-glutamyl thiol ester. The method employs aminoalkyl ligands
      coupled to a divinylsulfonyl-derivatized agarose matrix, and the length of the
      aminoalkyl spacer arm was found to be important for the effectiveness of the
      matrix. Optimal results were obtained with diaminododecyldivinylsulfonyl-agarose.
      Employing this matrix the thiol ester proteins C3, C4 and alpha 2M were isolated
      from human pregnancy serum. Application of the method to chicken and rainbow
      trout serum gave rise to isolation of several proteins including chicken and
      rainbow trout alpha 2M.

PMID- 9550107
TI  - Determination of some physicochemical parameters of microcystins (cyanobacterial
      toxins) and trace level analysis in environmental samples using liquid
      chromatography.
AB  - Some physicochemical parameters of three microcystin standards, known to be
      potent hepatotoxins produced by cyanobacteria, were determined using well defined
      chromatographic measurements. The logarithm of their retention factor on
      octadecylsilica (ODS) with water as the eluent, which is an estimation of the
      hydrophobicity of a molecule, was assessed at pH 7 at 3.9, 4.2 and 4.4 for
      microcystins-YR, -LR and -RR, respectively. Though being rather hydrophobic,
      microcystins also possess polar functions, namely carboxylic acids, amino and
      amido groups. The ionization of carboxylic groups occurs at pH values of 3.3-3.4.
      In environmental waters, microcystins are neutral or anionic. They are readily
      soluble in water, the solubility of microcystin-LR being higher than 1 g/l. Owing
      to their hydrophobicity and their polar functions, microcystins remain in the
      aqueous phase rather than being adsorbed on sediments or on suspended particulate
      matter. In a river water spiked with microcystins at 5 micrograms/l, only 10% was
      adsorbed on particles and 7% on the sandy sediment after three days. A method
      using solid-phase extraction on ODS followed by high-performance--or micro-
      liquid chromatography was optimized to detect microcystins at trace level in
      water. A clean-up was introduced to eliminate part of the interfering compounds
      coextracted during the sample percolation. Good recoveries (75-80%) were
      obtained. The method was linear, reproducible (with relative standard deviations
      ranging from 5 to 8%) and enabled the determination of microcystins at levels as
      low as 30 ng/l in drinking water and 100-200 ng/l in surface waters. The
      production of toxins by two strains of cyanobacteria was evaluated. Variations in
      the microcystin-LR content in the cells and in the medium of Microcystis
      aeruginosa PCC7806 were recorded over a five-week period. Toxin production was
      not correlated to the biomass but depended on the growth stage and was maximal at
      the end of the exponential growth phase. The release of toxin in water occurred
      essentially in old cultures where microcystin-LR was determined at concentrations
      of 170 and 280 micrograms/l in the media of M. aeruginosa PCC7806 and M.
      aeruginosa PCC7813, respectively. Other microcystins are likely to be synthesized
      by these strains. But owing to the lack of standards, mass spectrometric
      detection is required for further identification. This study points out the need
      of having other standards for water quality monitoring.

PMID- 9550108
TI  - Chiral and nonchiral determination of ketoprofen in pharmaceuticals by capillary
      zone electrophoresis.
AB  - The new method for the enantiomeric resolution of various 2-arylpropionic acids
      by capillary zone electrophoresis (CZE) using heptakis-tri-O-methyl-beta
      cyclodextrin as chiral selector was applied to the determination of ketoprofen in
      different commercially-available pharmaceutical preparations. The analyte was
      determined under chiral and nonchiral conditions (viz. in the presence and
      absence of 50 mM heptakis-tri-O-methyl-beta-cyclodextrin in the background
      electrolyte), with significantly similar results and relative standard deviations
      from 1.2 to 6.5% in both cases. The limits of detection and determination for the
      inactive enantiomer, R-(-)-ketoprofen, were calculated to be 7.0 x 10(-7) and 1.6
      x 10(-6) M, respectively. The proposed method was successfully used to determine
      enantiomeric purity in the drugs studied, with results comparable to those
      provided by the chiral HPLC method.

PMID- 9550109
TI  - Circadian rhythms.
AB  - 1997 marks the 25th anniversary of the discovery of the master circadian
      pacemaker in mammals in the hypothalamic suprachiasmatic nucleus. Remarkable
      progress has been made over the last 25 years in elucidating the physiological
      mechanisms involved in the entrainment, generation and expression of circadian
      rhythms at the cellular and systems levels. The recent discovery and cloning of
      the first mammalian clock gene is expected to lead to rapid advances in the
      understanding of the genetic and molecular mechanisms underlying circadian
      rhythmicity in mammals. Indeed, the impressive and extensive database on
      circadian rhythms in mammals obtained over the past 25 years provides a
      foundation for making rapid progress in utilizing future genetic and molecular
      findings for discovering the fundamental mechanisms controlling 24-hour temporal
      organization.

PMID- 9550110
TI  - Processes underlying sleep regulation.
AB  - Sleep is regulated by homeostatic, circadian and ultradian processes. Slow waves
      and sleep spindles are EEG markers of sleep processes which have counterparts at
      the cellular level. The interaction of homeostatic and circadian sleep regulation
      has been formalized in the two-process model and validated in experiments. Sleep
      is not only a global brain phenomenon but also a regional cerebral process whose
      intensity may be influenced by prior activity during waking.

PMID- 9550111
TI  - Effect of seasonal changes in daylength on human neuroendocrine function.
AB  - The circadian pacemaker imposes stereotypic patterns of daily variation on the
      activity of human neuroendocrine systems. In a number of cases, these patterns
      exhibit waveforms that are characterized by distinct diurnal and nocturnal
      periods with relatively discrete transitions between them (corresponding to a
      biological day, a biological dusk, a biological night, and a biological dawn). In
      humans, for example, diurnal periods of absence of melatonin secretion, low
      prolactin secretion, and falling levels of cortisol alternate with nocturnal
      periods of active melatonin secretion, high prolactin secretion and rising levels
      of cortisol. In response to light, the circadian pacemaker synchronizes the
      timing of the biological day and night so that their timing and duration are
      appropriately matched with the timing and duration of the solar day and night. As
      the pacemaker carries out this function, it is able to adjust the duration of the
      biological day and night to match seasonal variation in the duration of the solar
      day and night. Thus, after humans have been chronically exposed to long nights
      (scotoperiods), the duration of nocturnal periods of active melatonin secretion,
      high prolactin secretion and rising levels of cortisol is longer than it is after
      they have been chronically exposed to short nights. Furthermore, the sleep
      related peak of growth hormone secretion is half as high after exposure to long
      nights as it is after exposure to short nights. These responses to seasonal
      changes in duration of the natural scotoperiod are suppressed in most individuals
      - especially men - who live in modern urban environments in which they are
      exposed to artificial light after dark and artificial darkness during the
      daytime.

PMID- 9550112
TI  - Effects of hormones on sleep.
AB  - Administration of hormones to humans and animals results in specific effects on
      the sleep electroencephalogram (EEG) and nocturnal hormone secretion. Studies
      with pulsatile administration of various neuropeptides in young and old normal
      controls and in patients with depression suggest they play a key role in sleep
      endocrine regulation. Growth hormone (GH)-releasing hormone (GHRH) stimulates GH
      and slow wave sleep (SWS) and inhibits cortisol, whereas corticotropin-releasing
      hormone (CRH) exerts opposite effects. Changes in the GHRH:CRH ratio contribute
      to sleep-endocrine aberrations during normal ageing and acute depression. In
      addition, galanin and neuropeptide Y promote sleep, whereas, in the elderly,
      somatostatin impairs sleep. The rapid eye movement (REM)-nonREM cycle is
      modulated by vasoactive intestinal polypeptide. Cortisol stimulates SWS and GH,
      probably by feedback inhibition of CRH. Neuroactive steroids exert specific
      effects on the sleep EEG, which can be explained by gamma-aminobutyric acid(A)
      receptor modulation.

PMID- 9550113
TI  - Ultradian rhythms in hydromineral hormones.
AB  - The maintenance of hydromineral homeostasis depends on the coordinated action of
      arginine vasopressin (AVP), atrial natriuretic peptide (ANP), the renin
      angiotensin-aldosterone system and other recently identified endocrine or
      paracrine hormones. Several reports have pointed out the changes in urinary
      excretion and osmolality during the sleep-wake cycle and the rapid eye movement
      (REM)-non(N)REM sleep cycles. No such changes occur for ANP levels which have a
      flat profile over 24 h. The pulsatile fluctuations of AVP are described as
      random. The ultradian rhythm of plasma renin activity (PRA) depends on the
      regularity of the REM-NREM sleep cycles and the nocturnal curves reflect all
      disturbances in the internal sleep structure. A study with a shift in the normal
      sleep time clearly demonstrated that both PRA and aldosterone oscillations are
      sleep-stage dependent. These hormones could account for the ultradian variations
      in renal function. The nocturnal oscillations in sympathovagal balance may play
      an additional role. It is suggested that a central generator synchronizes
      endocrine, renal, autonomic and sleep processes.

PMID- 9550114
TI  - The physiology and pharmacology of melatonin in humans.
AB  - Melatonin (MLT) is a methoxyindole secreted principally by the pineal gland. It
      is synthesized at night under normal environmental conditions. The endogenous
      rhythm of secretion is generated by the suprachiasmatic nuclei and entrained by
      the light/dark cycle. Light is able to both suppress or entrain MLT production on
      light schedule. The nyctohemeral rhythm of this hormone can be determined by
      repeated measurement of plasma or saliva MLT or urine sulfatoxy-MLT, the main
      hepatic metabolite. MLT can be considered as the output (the hand) of the
      endogenous clock. Since the regulating system follows a central and sympathetic
      nervous pathway, an abnormality at any level could unspecifically modify the MLT
      secretion, especially in patients with sympathalgia or dysautonomia. MLT plays
      the role of an endogenous zeitgeber on core temperature or sleep-wake cycle.
      Exogenous MLT is able to influence the endogenous secretion of the hormone
      according to a phase-response curve. There are practical implications for this
      property in situations when biological rhythms are disturbed (jet-lag syndrome,
      delayed sleep phase syndrome, insomnia in blind people, shift-work, insomnia in
      elderly people). Improvement of pharmaceutical forms (controlled release
      preparations) or development of MLT analogs could lead to decisive progress.

PMID- 9550115
TI  - Therapeutic applications of melatonin and related compounds.
AB  - Increasing knowledge of the pharmacological effects of melatonin has suggested
      various possible therapeutic applications for the hormone. Because, as a natural
      substance, melatonin cannot be patented, melatonin-related compounds have been
      synthesized by industrial groups. The scope of such compounds is also to
      specifically target the recently discovered melatonin receptor subtypes. The
      sleep-inducing properties of melatonin are disputed, but are distinct from those
      of benzodiazepines. The observed effects on sleep latency or sleep efficiency,
      which remain to be confirmed, could be accounted for by the effects of melatonin
      on core body temperature and on circadian rhythms. There is also an urgent need
      for safety data, both in animals and in humans, particularly when long-term use
      is envisaged.

PMID- 9550116
TI  - Alterations of circadian rhythmicity and sleep in aging: endocrine consequences.
AB  - All 24-hour endocrine rhythms partially reflect the interaction of circadian
      rhythmicity with sleep-wake homeostasis but their relative contributions vary
      from one system to another. In older adults, many 24-hour rhythms are dampened
      and/or advanced, including those of cortisol and GH. Amplitude reduction and
      phase advance of 24-hour rhythms may represent age-related changes in the central
      nervous systems underlying circadian rhythmicity and sleep-wake homeostasis. Age
      related alterations in circadian function could also reflect decreased exposure
      and/or responsivity to the synchronizing effects of both photic (e.g. light
      exposure) and nonphotic (e.g. social cues) inputs. There are pronounced age
      related alterations in sleep quality in aging which consist primarily of a marked
      reduction of slow-wave sleep, a reduction in REM stages and a marked increase in
      the number and duration of awakenings interrupting sleep. Alterations in slow
      wave sleep occur abruptly in young adulthood (30-40 years of age) whereas
      disturbances in amounts of REM and wake appear more gradually. This article
      reviews evidence indicating that deficits in characteristics of sleep-wake
      homeostasis and circadian function may mediate age-related alterations in
      somatotropic and corticotropic function. Because sleep loss in young subjects
      results in endocrine disturbances which mimic those observed in aging, it is
      conceivable that the decrease in sleep quality which characterizes aging may
      contribute to age-related alterations in hormonal function and their metabolic
      consequences.

PMID- 9550117
TI  - Endocrine secretions under abnormal light-dark cycles and in the blind.
AB  - Both endogenous and exogenous factors are involved in regulation of endocrine
      secretions. Among the exogenous ones, light plays an important role both in
      animals and in humans. Pineal gland mediates light action on the endocrine
      system, by means of variations of melatonin (MT) secretion. Here we discuss about
      the influence of abnormal light-dark cycles and in particular of blindness on
      pineal and pituitary secretions and on those of correlated glands. MT secretion
      is usually inhibited by light: thus it reaches the highest levels at night.
      Exposure to short or long photoperiod causes variations in circadian or infradian
      MT rhythmicity. Blind patients can show higher daytime levels with a phase
      advanced or phase-delayed circadian rhythm. Lack of light stimulus affects
      cortisol rhythm shifting the zenith of secretion and inducing a free-running
      rhythm. Blindness can abolish nocturnal growth hormone (GH) peak and impair the
      GH response to some stimuli; moreover it impairs the growth of affected patients.
      Light stimulus influences favorably gonadal function both in animals and in man.
      In animals, sexual activity and gonadal function decline during the seasons with
      reduced luminosity. A similar finding has been described in women living in a
      region with a strong seasonal contrast in luminosity. Blindness can impair
      luteinizing hormone, follicle-stimulating hormone, prolactin and testosterone
      secretion in prepubertal boys causing pubertal delay or more severe hypogonadism;
      it can affect pubertal development and fertility in women. Light can influence
      thyroid function in animals. Lack of light stimulus in blind man seems to cause
      different effects on thyroid function before and after puberty. Increase of free
      thyroid hormone levels has been found in prepubertal but not in adult blind
      patients, probably due to a resetting of the threshold for thyrotropin feedback
      suppression after puberty in these patients.

PMID- 9550118
TI  - Sleep and circadian disturbances in shift work: strategies for their management.
AB  - More and more businesses are providing their full range of services 24 h a day, 7
      days a week, thus forcing their employees to work either rotating shifts or fixed
      night shifts. Dictates of our endogenous circadian clock prevent our brains and
      bodies to be indefinitely adaptable to those work schedules. Shift work
      operations are thus associated with serious healthy and social problems for the
      workers. Various interventions can counteract circadian desynchronization, sleep
      disturbances, and social disruption associated with shift work: changes in work
      schedules, sleeping and napping strategies, use of appropriately timed exposure
      to bright light, experimental drug treatments, or exercise.

PMID- 9550119
TI  - Gonadotropin pulsations across development.
AB  - Initiation and maintenance of the reproductive axis in the human is contingent
      upon the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the
      hypothalamus. In man, tracking endogenous GnRH secretion relies on frequent
      peripheral sampling of three glycoprotein products of the gonadotrope,
      luteinizing hormone (LH), follicle-stimulating hormone (FSH) and free alpha
      subunit (FAS). FAS is superior to LH as a surrogate marker of GnRH secretory
      dynamics in those circumstances where GnRH secretion is rapid or where the
      pituitary LH response is low. The pattern of GnRH secretion is constantly
      changing across development; from high levels during the neonatal period, through
      a period of quiescence in mid-childhood, followed by sleep-entrained reactivation
      of the reproductive axis at the onset of puberty, ultimately culminating in the
      adult pattern of pulsatile secretion which in the male is approximately every 2 h
      and in the female varies with the stage of the menstrual cycle. This episodic
      mode of secretion allows differential impact of feedback mechanisms on the GnRH
      neurons and facilitates the maintenance of the reproductive axis during periods
      of stress by allowing frequency and amplitude modulations.

PMID- 9550120
TI  - Interaction between menstrual cyclicity and gonadotropin pulsatility.
AB  - Pulsatile gonadotropin secretion is a critical endocrine component of the
      regulation of the normal menstrual cycle. Pulsatile luteinizing hormone (LH)
      secretion changes dynamically across the menstrual cycle. Derangements of
      pulsatile LH secretion are found in virtually every menstrual disorder. This
      article summarizes the key features of pulsatile LH secretion in the normal
      menstrual cycle and in ovulatory disorders.

PMID- 9550121
TI  - Central nervous system control of thyrotropin secretion during sleep and
      wakefulness.
AB  - Thyrotropin (TSH) is a pulsatile secreted hormone with a pronounced circadian
      rhythmicity and a characteristic nightly surge based on an augmentation of
      pulsatile release. A number of physiological factors influence TSH secretion via
      an alteration in the amount of pulsatile released hormone. An increase in
      somatostatinergic tone during fasting appears to decrease TSH pulse amplitude and
      sequentially mean TSH serum levels. In contrast, blockade of dopaminergic tone by
      metoclopramide infusion when circulating TSH levels are low during the afternoon
      hours increase TSH pulse amplitude to levels comparable to the nightly TSH surge
      suggesting a physiological dampening of TSH pulse amplitude by dopamine during
      the daytime.

PMID- 9550122
TI  - Temporal profiles and clinical significance of pulsatile insulin secretion.
AB  - In this article, recent experiments are reviewed which have addressed the role of
      oscillatory insulin secretion in the pathophysiology of glucose intolerance and
      diabetes. The ultradian oscillations of insulin secretion appear to be an
      integral part of the feedback loop between glucose and insulin secretion and as a
      result are abnormal in states of glucose intolerance. Treatment of impaired
      glucose tolerance with troglitazone, a thiazolidinedione that improves insulin
      sensitivity, leads to an improvement in the ability of the beta-cell to sense and
      respond to a glucose stimulus restoring the ability of glucose to entrain the
      ultradian oscillations. The rapid oscillations of insulin secretion appear to be
      an inherent feature of the cellular mechanisms of insulin secretion since they
      persist in the isolated perfused pancreas and in perifused islets. These
      oscillations are paralleled by changes in intracellular Ca2+ and are also
      abnormal in states of glucose intolerance and diabetes. Available evidence
      indicates that these alterations are due to decreased expression of voltage
      dependent Ca2+ channels on the beta-cell membrane.

PMID- 9550123
TI  - Ultradian pulsatility of plasma glucose and insulin secretion rate: circadian and
      sleep modulation.
AB  - Insulin release is a complex oscillatory process with rapid pulses (10 min)
      superimposed on slower circhoral oscillations (50-100 min). The exact mechanism
      of the circhoral oscillations, which are probably in part the consequence of a
      negative feedback loop linking glucose and insulin secretion rate, remains
      unclear. Stimulatory effects of sleep on insulin secretion are achieved by an
      enhancement of the oscillation amplitude which could be partly mediated by GH.
      The different patterns observed after acute or chronic shift of sleep suggest
      however an interaction between sleep influence and circadian rhythmicity, as
      described for numerous pituitary hormones. The intra-sleep awakenings have a
      modulatory effect on glucose levels but no systematic relationship exists between
      glucose or insulin secretion rate oscillations and the REM-NREM sleep cycles.
      Irrespective of the mechanisms involved, sleep or GH stimulatory effects result
      from a modulation of the oscillation amplitude rather than of their frequency
      which is probably an important feature of insulin efficacy.

PMID- 9550124
TI  - The roles of time of day and sleep quality in modulating glucose regulation:
      clinical implications.
AB  - Consistent variations in glucose regulation across the 24-hour cycle are present
      in normal subjects. These diurnal variations are altered in various states of
      impaired glucose tolerance (aging, obesity, diabetes). Changes in insulin
      secretion, clearance and/or action across the day have been demonstrated. Studies
      in subjects receiving continuous intravenous glucose infusion have shown that
      major alterations of glucose tolerance occur during sleep and that sleep quality
      markedly influences glucose utilization. Diurnal variations in glucose tolerance
      result from the alternation of wake and sleep states as well as from intrinsic
      effects of circadian rhythmicity. The important roles of physiological variations
      in levels of counterregulatory hormones which are markedly dependent on sleep
      (i.e. growth hormone) or circadian rhythmicity (i.e. cortisol) have only begun to
      be appreciated. The modulatory effects of sleep and circadian rhythmicity on
      glucose regulation may have important clinical implications for the diagnosis and
      treatment of abnormalities of carbohydrate metabolism.

PMID- 9550125
TI  - Expression and degradation of rat androgen receptor following castration,
      testosterone replacement and antiandrogens administration: analysis by Western
      blot and immunohistochemistry.
AB  - To elucidate the autoregulation of androgen receptor (AR) by androgen and
      antiandrogen, Western blot analysis and immunohistochemical study were performed.
      Castration reduced the immunodetected AR content, and nuclear staining was lost
      without cytoplasmic staining. Testosterone (T) supplement restored AR content.
      Quick response of AR content restoring following single administration of T was
      observed 48 hours after castration. The recovery of AR content detected by
      Western blot under each condition was accompanied by recovery of the reduced
      unclear staining intensities in the epithelia. Neither steroidal nor non
      steroidal antiandrogens, chlormadinone acetate and flutamide, altered the AR
      content in normal rat ventral prostate 5, 12, 24 or 48 hours after single
      administration. Furthermore, neither of the drugs at various doses altered AR
      levels 12 hours after single administration. In summary, the rat AR is
      upregulated by androgen. Single administration of antiandrogens have no effect on
      immunodetected AR content.

PMID- 9550127
TI  - Signal transduction of granulocyte macrophage-colony stimulating factor in a
      human endothelium-derived cell line.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) regulates the growth
      and differentiation of hematopoietic cells and is also involved in angiogenesis.
      The induction of protein tyrosine phosphorylation is critical for cytokines and
      growth factor-mediated signal transduction. The protein tyrosine kinase (PTK),
      JAK2 is involved in signaling through a number of cytokine receptors, including
      GM-CSF receptors. In the present study, we investigated the effect of GM-CSF on
      the cell cycle and protein tyrosine phosphorylation in a human endothelial cell
      derived cell line, EA.hy 926 cells. GM-CSF induced the cell cycle progression and
      tyrosine phosphorylation of cellular proteins including JAK2 kinase in EA.hy 926
      cells. Herbimycin A, a PTK inhibitor, completely blocked the GM-CSF-induced cell
      cycle progression, protein tyrosine phosphorylation and JAK2 kinase activation in
      EA.hy 926 cells. Our results demonstrate that protein tyrosine phosphorylation
      and JAK2 kinase activation are closely related to the GM-CSF-mediated signal
      transduction and growth in vascular endothelial cells, and suggest the efficacy
      of herbimycin A in controlling angiogenesis.

PMID- 9550126
TI  - Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD
      4833 Glucose Clamp Study Group, Japan.
AB  - We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin
      stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid
      metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM).
      Twenty NIDDM subjects (mean age 58.2+/-9.4 year, body mass index (BMI) 23.9+/-3.4
      kg/ m2 (mean+/-S.D.], three with diet alone, 17 with sulfonylureas [SU])
      participated in this trial from five diabetes clinics. Euglycemic (5.3
      mmol/liter) hyperinsulinemic (insulin infusion rate 9 micromoles x kg[-1] x min[
      1]) clamp studies were performed before and after oral administration of
      pioglitazone (30 mg/day) for 87+/-10 days. The Rd significantly improved from
      5.5+/-2.5 to 8.3+/-3.1 mg x kg(-1) x min(-1). Fasting plasma glucose (FPG) level
      significantly decreased from 11.0+/-2.0 mmol/liter to 8.9+/-1.1 mmol/liter with a
      significant improvement in the hemoglobin A1c level from 9.2+/-1.8% to 8.3+/
      1.5%. Fasting serum insulin and C peptide levels decreased from 83+/-36
      pmol/liter and 0.62+/-0.21 nmol/liter to 66+/-29 pmol/liter and 0.58+/-0.25
      nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels
      significantly decreased with concomitant increase of fasting serum HDL
      cholesterol levels from 1.2+/-0.2 to 1.5+/-0.3 mmol/liter. The change in Rd
      between before and after pioglitazone administration correlated with baseline
      values of FPG (rho=0.633), serum insulin (rho=0.653), BMI (rho=0.456), Rd (rho
      0.558) and 1,5-AG (rho=-0.522). These data indicate that pioglitazone enhances
      the insulin action in NIDDM patients on diet alone or SU, and thereby improves
      both plasma glucose level and lipid profiles.

PMID- 9550128
TI  - Homology of E2 gene in 8 child-mother pairs infected with hepatitis C virus.
AB  - The frequency of genetic homology of hepatitis C virus (HCV) E2 gene in 8 child
      mother pairs was investigated. The route of HCV infection of all children
      suggested mother-to-child infection by their past history. In this study, we
      analyzed at least 5 complementary DNA (cDNA) clones for each case. In 6 of the 8
      (75%) child-mother pairs, for the region between hypervariable region (HVR)-1 and
      HVR-2, the similarity of the nucleotide sequence of all 5 cDNA clones between
      each child and the mother was higher than that between the child and the other
      children, the other mothers and the sequences from GenBank. One of the 8 (13%)
      child-mother pairs showed a great similarity in parts of all cDNA clones. This
      was also confirmed by phylogenetic analyses of the sequences of cDNA clones from
      families and that from GenBank. These results suggested that the homology search
      of nucleotide sequence of this region was useful to confirm mother-to-child
      transmission of HCV.

PMID- 9550129
TI  - Urban-rural difference in cereal consumption by people in Shandong Province,
      China.
AB  - In October, 1996, 24-hour food duplicate samples were collected from two groups
      of 50 adult women each; one group was in Jinan, the capital city of Shandong
      Province in China, and the other in a farming village of Baiquan in Zhangqiu area
      some 30 km away from the city. Perusal of food menus showed that wheat, rice,
      foxtail millet and maize were major cereals for the two groups. Nutritional
      analysis of the food duplicate samples were conducted taking advantage of weight
      of each food item and the standard food composition tables for Chinese
      populations. Whereas wheat was the leading source in both groups (73% of cereal
      based energy in the city and 64% in the village), further urban-rural comparison
      showed that women in the village took substantial amounts of millet (19%) and
      maize (12%) in contrast to small consumption by the city people (millet by 5% and
      maize by 2%). Rice consumption was larger in the city (20%) than in the village
      (5%). The differences between the two groups were all significant for each of the
      four cereals. Nutritional significance of consumption of maize in particular and
      also that of millet were discussed.

PMID- 9550130
TI  - Cyclooxygenase metabolites possibly produced by endothelial cells mediate the
      lung injury caused by mechanically stimulated leukocytes.
AB  - To determine whether mechanically stimulated leukocytes increase pulmonary
      vascular permeability and resistance and, if so, whether cyclooxygenase
      metabolites mediate the increase, we assessed the effects of stimulated and
      unstimulated leukocytes, and of a cyclooxygenase inhibitor on pulmonary vascular
      permeability and resistance in isolated perfused lungs from Sprague-Dawley rats.
      Leukocytes were stimulated by gentle agitation in a glass container for 10
      seconds. After baseline measurements were made, stimulated or unstimulated
      leukocytes were added to the perfusate. The effects of the cyclooxygenase
      inhibitor, meclofenamate, on the pulmonary vascular filtration coefficient and
      pulmonary vascular resistance were measured. In the rats that received stimulated
      leukocytes, the pulmonary vascular filtration coefficient and the vascular
      resistance were about 2.5 times and 3.3 times higher, respectively, than those in
      the rats that received unstimulated leukocytes. These increases were completely
      and partly blocked by meclofenamate. Histological examination indicated that
      meclofenamate did not prevent the adhesion of leukocytes to the pulmonary
      vascular endothelium. These findings suggest that mechanically stimulated
      leukocytes increase pulmonary vascular permeability and that cyclooxygenase
      metabolites produced by endothelial cells may injure the cells.

PMID- 9550131
TI  - A case report of salivary duct carcinoma.
AB  - We present a 65-year-old man with an enlarged mass in the right parotid gland. A
      fine-needle aspiration cytology suspected Warthin's tumor. The ill-defined margin
      of the tumor in diagnostic imaging and unexpected clinical course of the
      occurrence of facial nerve paralysis suggested malignant neoplasm. The patient
      was treated with surgical resection of the primary site and neck following
      radiation therapy. Pathologic diagnosis was a salivary duct carcinoma. Difficulty
      in early diagnosis of this tumor may result in local extension, early metastasis
      to regional lymph nodes and distant sites, and death.

PMID- 9550132
TI  - Introduction to histology of the ventricular walls of the brain.

PMID- 9550133
TI  - Ependymal development, proliferation, and functions: a review.
AB  - A survey of the literature shows that proliferation of ependyma occurs largely
      during the embryonic and early postnatal periods of development in most species.
      Differentiation of these cells proceeds along particular regional and temporal
      gradients as does the expression of various cytoskeletal (vimentin, cytokeratins,
      glial fibrillary acidic protein) and secretory proteins (S-100). Turnover
      declines significantly postnatally, and only low levels of residual activity
      persist into adulthood under normal conditions. Although the reported response of
      ependyma to injury is somewhat equivocal, only limited regenerative capacity
      appears to exist and to varying degrees in different regions of the neuraxis.
      Proliferation has been most often observed in response to spinal cord injury.
      Indeed, the ependyma plays a significant role in the initiation and maintenance
      of the regenerative processes in the spinal cord of inframammalian vertebrates.
      In the human, however, ependyma appears never to regenerate at any age nor re
      express cytoskeletal proteins characteristic of immature cells. The functions of
      ependyma including tanycytes, a specialized form of ependymal cell that persists
      into adulthood within circumscribed regions of the nervous system, are still
      largely speculative. Fetal unlike mature ependyma is believed to be secretory and
      is believed to play a role in neurogenesis, neuronal differentiation/axonal
      guidance, transport, and support. In the adult brain, mature ependyma is not
      merely an inert lining but may regulate the transport of ions, small molecules,
      and water between the cerebrospinal fluid and neuropil and serve an important
      barrier function that protects neural tissue from potentially harmful substances
      by mechanisms that are still incompletely understood.

PMID- 9550134
TI  - Histochemistry and immunocytochemistry of the developing ependyma and choroid
      plexus.
AB  - The adult human ependyma expresses no intermediate filament proteins or secretory
      proteins; the fetal ependyma shows strong immunocytochemical (ICC) expression of
      vimentin, glial fibrillary acidic protein (GFAP), cytokeratins (CKs) of high
      molecular weight, glycoproteins, and S-100beta protein. Each has a precise and
      specific spatial distribution within the developing ependyma and a predictable
      time of appearance and regression in each region of the ventricular system.
      Several are coexpressed, but some appear earlier or persist longer than others.
      Secretory proteins of ependymal cells are important in several developmental
      processes such as the guidance of axonal growth cones. GFAP is not expressed in
      the floor plate ependyma at any stage of development, unlike vimentin and CK. The
      choroid plexus epithelium is a specialized ependyma, with an ICC profile that
      differs from the surface ependyma: vimentin, CK, and S-100beta protein continue
      to be expressed throughout fetal and adult life, but GFAP is not expressed.
      Certain cerebral malformations are associated with specific ICC abnormalities:
      ependymal S-100beta protein continues to be immunoreactive in disorders of
      neuroblast migration; ependymal vimentin is focally upregulated in Chiari
      malformations and congenital aqueductal stenosis. Other mammalian and
      nonmammalian species have characteristic profiles of ependymal immunoreactivity
      to the same proteins expressed in humans but exhibit interspecific differences.

PMID- 9550135
TI  - Tanycytes and pituicytes: morphological and functional aspects of neuroglial
      interaction.
AB  - The hypothalamo-hypophyseal system is supplied with two types of specialized
      glial cells that interact in neuroendocrine functional dynamics: the tanycytes
      and the pituicytes. Tanycytes are the dominating glial cells within the median
      eminence. Similar to radial glia, they extend from the floor of the third
      ventricle to the neurohemal surface of the median eminence. Pituicytes, as
      specialized astrocytes, are the main glial cells of the neural lobe. They are in
      intimate contact with the perivascular space of the sinusoidal vessels.
      Morphological similarities between the two cell types focus on their interaction
      with terminal branches of hypothalamic neurons in both regions of the
      neurohypophysis, the median eminence and the neural lobe. Release of hypothalamic
      hormones is apparently influenced by pituicytes and tanycytes. For instance, both
      types of cells are capable of closing or opening the access to the vessels.
      Thereby, in contrast to the "blood-brain-barrier" function of astrocytes,
      pituicytes and tanycytes display "brain-blood-barrier" functions. Pituicytes are
      characterized by the expression of specific membrane-bound receptors for opioids,
      vasopressin, and beta-adrenoceptors, indicating that they receive input by
      numerous neuroactive substances. Integration of these incoming signals may result
      in a regulation of neurosecretion, especially by morphological changes and by
      modulation of extracellular ion concentrations. Comparable modulatory mechanisms
      of tanycytes have not yet been elucidated in a convincing manner. Besides
      possible regulatory functions, tanycytes are considered to possess guiding
      functions for hypothalamic axons and to be involved in transport mechanisms
      between ventricle and blood vessels of the portal system.

PMID- 9550136
TI  - Origin, nature, and some functional considerations of intraventricular
      macrophages, with special reference to the epiplexus cells.
AB  - Intraventricular macrophages encompass the supraependymal, free-floating, and
      epiplexus (Kolmer) cells; the supraependymal cells lie in close apposition to the
      ventricular ependyma, the epiplexus cells are closely associated with the choroid
      plexus epithelium, and the free-floating cells are at a variable distance from
      the epithelial surface. Although the three cell types are regarded as one
      cellular entity, the epiplexus cells preponderate. On scanning electron
      microscopy, the epiplexus cells display diverse morphological forms, ranging from
      round to bipolar to stellate, and bear a variable number of cytoplasmic
      processes. Transmission electron microscopy shows the presence of large numbers
      of lysosomes. The phagocytic nature of epiplexus cells is shown by their intense
      staining for nonspecific esterase and active uptake of tracers, e.g., horseradish
      peroxidase and rhodamine isothiocynate, administered intravenously or
      intraperitoneally. The mode of entry of these tracers in the cerebral ventricles
      is by way of transepithelial transport. In rats, the population of
      intraventricular macrophages increases steadily after birth until 17 days of age;
      thereafter, their cell population remains relatively unchanged. The early upsurge
      is attributed to proliferation of residential cells and/or influx of circulating
      monocytes/stromal macrophages through the process of "emperipolesis." The
      immunophenotypic features of intraventricular macrophages are consistent with
      other mononuclear phagocytes being immunoreactive for OX-42, OX-18, OX-6, and OX
      1 and ED1 for the detection of CR3 receptors, MHC class I and II antigens,
      leucocyte common antigen, and macrophage antigen, respectively. The expression of
      these antigens is noticeably enhanced following the injection of
      lipopolysaccharide (LPS) into postnatal rats. Remarkably, the intraventricular
      macrophages are induced to express MHC class II (Ia) antigen after LPS or
      interferon-gamma injections. Furthermore, the expression of transferrin receptors
      as detected with OX-26 is also upregulated after these treatments. Epiplexus
      cells are also elicited to display a de novo expression of nitric oxide synthase
      like immunoreactivity following intracerebral injection of LPS. They also respond
      vigorously to a single nonpenetrative blast. Results of our series of studies
      suggest that, besides their primary function as scavenger cells, the
      intraventricular macrophages partake in possible immunological responses and iron
      regulation in the ventricular system or the brain as a whole.

PMID- 9550137
TI  - Actual problems of the cerebrospinal fluid-contacting neurons.
AB  - Cerebrospinal fluid (CSF)-contacting neurons form a part of the circumventricular
      organs of the central nervous system. Represented by different cytologic types
      and located in different regions, they constitute a CSF-contacting neuronal
      system, the most central periventricular ring of neurons in the brain organized
      concentrically according to our concept. Because the central nervous system of
      deuterostomian echinoderm starfishes and the prochordate lancelet is composed
      mainly of CSF-contacting-like neurons, we hypothesize that this cell type
      represents ancient cells, or protoneurons, in the vertebrate brain. Neurons may
      contact the ventricular CSF via their dendrites, axons, or perikarya. Most of the
      CSF-contacting nerve cells send their dendritic processes into the ventricular
      cavity, where they form ciliated terminals. These ciliated endings resemble those
      of known sensory cells. By means of axons, the CSF-contacting neurons also may
      contact the external CSF space, where the axons form terminals of neurohormonal
      type similar to those known in the neurohemal areas. The most simple CSF
      contacting neurons of vertebrates are present in the terminal filum, spinal cord,
      and oblongate medulla. The dendritic pole of these medullospinal CSF-contacting
      neurons terminates with an enlargement bearing many stereocilia in the central
      canal. These cells are also supplied with a 9 x 2 + 2 kinocilium that may contact
      Reissner's fiber, the condensed secretory material of the subcommissural organ.
      The Reissner's fiber floating freely in the CSF leaves the central canal at the
      caudal open end of the terminal filum in lower vertebrates, and open
      communication is thus established between internal CSF and the surrounding tissue
      spaces. Resembling mechanoreceptors cytologically, the spinal CSF-contacting
      neurons send their axons to the outer surface of the spinal cord to form
      neurosecretory-type terminals. They also send collaterals to local neurons and to
      higher spinal segments. In the hypothalamic part of the diencephalon, neurons of
      two circumventricular organs, the paraventricular organ and the vascular sac, of
      the magnocellular neurosecretory nuclei and several parvocellular nuclei, form
      CSF-contacting dendritic terminals. A CSF-contacting neuronal area also was found
      in the telencephalon. The CSF-contacting dendrites of all these areas bear
      solitary 9 x 2 + 0 cilia and resemble chemoreceptors and developing
      photoreceptors cytologically. In electrophysiological experiments, the neurons of
      the paraventricular organ are highly sensitive to the composition of the
      ventricular CSF. The axons of the CSF-contacting neurons of the paraventricular
      organ and hypothalamic nuclei terminate in hypothalamic synaptic zones, and those
      of magno- and parvocellular neurosecretory nuclei also form neurohormonal
      terminals in the median eminence and neurohypophysis. The axons of the CSF
      contacting neurons of the vascular sac run in the nervus and tractus sacci
      vasculosi to the nucleus (ganglion) sacci vasculosi. Some hypothalamic CSF
      contacting neurons contain immunoreactive opsin and are candidates to represent
      the "deep encephalic photoreceptors." In the newt, cells derived from the
      subependymal layer develop photoreceptor outer segments protruding to the lumen
      of the infundibular lobe under experimental conditions. Retinal and pineal
      photoreceptors and some of their secondary neurons possess common cytologic
      features with CSF-contacting neurons. They contact the retinal photoreceptor
      space and pineal recess, respectively, both cavities being derived from the third
      ventricle. In addition to ciliated dendritic terminals, there are
      intraventricular axons and neuronal perikarya contacting the CSF. Part of the CSF
      contacting axons are serotoninergic; their perikarya are situated in the raphe
      nuclei. Intraventricular axons innervate the CSF-contacting dendrites,
      intraventricular nerve cells, and/or the ventricular surface of the ependyma.
      (ABSTRACT TRUNCATED)

PMID- 9550138
TI  - Developing grasshopper neurons show variable levels of guanylyl cyclase activity
      on arrival at their targets.
AB  - The ability of certain grasshopper neurons to respond to exogenously applied
      donors of nitric oxide (NO) by producing cyclic GMP (cGMP) depends on their
      developmental state. ODQ, a selective blocker of NO-sensitive guanylyl cyclase,
      blocks cGMP production at 10(-5) M, thus confirming the nature of the response.
      Experiments in which the distal axon is separated from its proximal stump before
      application of an NO donor show that guanylyl cyclase is distributed uniformly
      throughout the neuron. In the locust abdomen, where segments are formed
      sequentially, the pattern of guanylyl cyclase up-regulation is predictable and
      sequential from anterior to posterior. There are two patterns of innervation by
      cGMP-expressing motor neurons. In the first, typified by muscle 187, an
      innervating neuron begins to be NO responsive on arrival at its muscle and
      continues to be so over most of the remainder of embryonic development, including
      the formation of motor end plates. In the second, typified by a neuron
      innervating muscle 191, the neuron extends well along the muscle, apparently
      laying down a number of sites of contact with it, before it becomes NO
      responsive. In both patterns, however, NO responsiveness marks the neuron's
      transition from growth cone elongation to the production of lateral branches.
      Individual muscles receive innervation from multiple motor neurons, some of which
      express transient NO sensitivity during development and others which do not. With
      the exception of the leg motor neuron SETi, the first motor neuron to reach any
      muscle is usually not NO responsive. We suggest that cGMP plays a role in, or
      reflects, the early stages of communication between a target and specific
      innervating neurons.

PMID- 9550139
TI  - Comparison of neural elements in sexually dimorphic segments of the grasshopper,
      Schistocerca americana.
AB  - A uniquely female behavior in grasshoppers, oviposition, is driven by neural
      circuitry in the terminal abdominal segments of the female's central nervous
      system. Because it is known that the embryonic pattern of neuroblasts is sexually
      monomorphic in these animals, we were interested to know how the central nervous
      system of adults is organized to support the obvious behavioral dimorphism. Here,
      we compare three classes of identifiable adult neurons: ovipositor motor neurons,
      efferent dorsal unpaired median (DUM) neurons, and DUM interneurons in the eighth
      abdominal neuromere. Cobalt backfills of the eighth tergal nerves revealed
      identical complements of motor neurons in males and females. Included among these
      neurons in the male were putative homologues of two sets of ovipositor muscle
      motor neurons. Whereas these motor neurons supply two ovipositor muscles in the
      female, they are divided to supply three muscles in males. The eighth abdominal
      neuromere of both sexes contained seven efferent DUM neurons, but peripheral axon
      projections varied between males and females in accordance with gender-specific
      targets. In the eighth neuromere of females, some 22 small cell bodies of DUM
      interneurons were stained with Toluidine blue, whereas only three male DUM
      interneurons were found. Male muscle homologues were induced to express a
      rhythmical motor pattern by experimental methods that activate the oviposition
      pattern in females. The induced pattern in males is of unknown behavioral
      significance. Although oviposition normally occurs only after sexual maturity,
      the motor pattern could be activated at all life stages in females, including
      embryos, as early as 90% of embryonic development.

PMID- 9550140
TI  - Autoradiographic localisation of [3H]-SCH23390 and [3H]-spiperone binding sites
      in honey bee brain.
AB  - In the brain of the honey bee, dopamine receptors have been identified by using
      the vertebrate D1 dopamine antagonist [3H]-SCH23390 and the vertebrate D2
      dopamine antagonist [3H]-spiperone. This study uses light microscope
      autoradiography to investigate the anatomical distributions of the binding sites
      labelled by [3H]-SCH23390 and [3H]-spiperone in tissue sections cut at three
      depths from the anterior surface of the brain. The binding of these radioligands
      differed significantly, in both density and distribution. Specific binding of
      [3H]-SCH23390, defined by using 5 x 10(-6) M cis-(Z)-flupentixol, was densest in
      regions of somata, such as the deutocerebral somatal rind, the somatal layer
      beneath the calyces of the mushroom bodies and the ventral protocerebral somatal
      group. High levels of [3H]-SCH23390 binding were also measured in the lateral
      protocerebrum. [3H]-Spiperone binding site density estimates were consistently
      lower than those of [3H]-SCH23390. Specific binding of [3H]-spiperone, determined
      by subtracting binding in the presence of 10(-4) M domperidone from the total
      binding, was highest in the alpha lobes, beta lobes, and calyces of the mushroom
      body neuropil. Relatively high binding was also measured in the central body and
      lateral protocerebral neuropil. These results suggest that the distribution of
      dopamine receptors in the brain of the bee is subtype specific, and they support
      the view that dopamine plays many roles in the insect central nervous system.

PMID- 9550141
TI  - Normal and injury-induced sympathetic innervation of rat dorsal root ganglia
      increases with age.
AB  - In rats, partial injury to a peripheral nerve often leads to sympathetically
      maintained pain (SMP). In humans, this condition is especially apparent in the
      elderly. Nerve injury also causes perivascular sympathetic axons to sprout into
      the dorsal root ganglion (DRG), forming a possible anatomical substrate for SMP.
      Here, we describe the effects of chronic sciatic nerve constriction injury (CCI)
      in young (3 months) and old (16 months) rats on neuropathic pain behavior and on
      sympathetic sprouting in DRG. Behavioral tests assessed changes in thermal
      allodynia and hyperalgesia and in mechanical allodynia. We found that 1)
      sympathetic innervation of the DRG increased naturally with age, forming
      pericellular baskets mainly around large DRG neurons, and that sympathetic fibers
      were often associated with myelinated sensory axons; 2) sympathetic fiber density
      following CCI was also greater in old than in young rats; and 3) in old rats,
      thermal allodynia was less pronounced than in young rats, whereas thermal
      hyperalgesia and mechanical allodynia were more pronounced. These results
      highlight the possibility that sympathetic sprouting in the DRG is responsible
      for the sympathetic generation or maintenance of pain, especially in the elderly.

PMID- 9550142
TI  - The region of the pontine parabrachial nucleus is a major target of dehydration
      sensitive CRH neurons in the rat lateral hypothalamic area.
AB  - Neurons in a restricted part of the lateral hypothalamic area (LHA) show
      increased expression of corticotropin-releasing hormone (CRH) mRNA as a
      consequence of cellular dehydration. In the present study, we have investigated
      the organization of their efferent projections by using anterograde and
      retrograde tracing techniques. Additionally, we have compared the distribution of
      CRH mRNA-containing neurons after cellular dehydration and intraventricular
      (i.c.v.) colchicine injections. Our results show that cellular dehydration
      activates a more restricted neuronal population than does i.c.v. colchicine.
      Iontophoretic injections of Phaseolus vulgaris leucoagglutinin (PHAL) were placed
      in the LHA of animals drinking hypertonic saline and their proximity to activated
      CRH neurons determined by in situ hybridization for CRH mRNA. Although labelled
      fibers from these injections were seen throughout the brain, the region of the
      parabrachial nucleus and nucleus of the solitary tract (NTS) were most
      conspicuous in also having CRH immunoreactive fibers. Injections of Fluoro-Gold
      placed in these two structures were used to confirm these findings in dehydrated
      animals. Significant numbers of neurons containing both Fluoro-Gold and CRH mRNA
      were seen in the lateral hypothalamus after injections in the lateral and medial
      parts of the parabrachial nucleus; far fewer were seen after injections in the
      NTS. These results strongly suggest that the CRH neurons in the LHA activated by
      cellular dehydration provide an input to the region of the parabrachial nucleus.
      The altered biochemical composition of this pathway may well be able to modify
      sensory and motor patterns both during and after dehydration.

PMID- 9550143
TI  - Developmental expression of VGF mRNA in the prenatal and postnatal rat.
AB  - VGF is a developmentally regulated, secretory peptide precursor that is expressed
      by neurons and neuroendocrine cells and that has its transcription and secretion
      induced rapidly by neurotrophins and by depolarization. To gain insight into the
      possible functions and regulation of VGF in vivo, we have characterized the
      distribution of VGF mRNA in the developing rat nervous system. VGF expression was
      first detectable at embryonic day 11.5 in the primordia of cranial, sympathetic,
      and dorsal root ganglia, and its distribution expanded throughout development to
      include significant expression throughout the brain, spinal cord, and retina of
      the adult rat. The earliest expression of VGF, therefore, appeared in the
      peripheral nervous system as developing neurons settled in their designated
      ganglia. In many regions of the brain, VGF mRNA levels were found to be highest
      during periods when axonal outgrowth and synaptogenesis predominate. Areas of the
      central nervous system that contain predominantly dividing cells never displayed
      any VGF mRNA expression, nor did the vast majority of nonneural tissues.

PMID- 9550144
TI  - Expression of VGF mRNA in the adult rat central nervous system.
AB  - VGF is a secretory peptide precursor that is expressed and processed by neuronal
      cells in a cell type-specific fashion. In addition, VGF transcription and
      secretion are rapidly and relatively selectively induced by neurotrophins and
      depolarization in vitro. To gain insight into the possible function(s) of VGF in
      the nervous system, we have carried out a detailed examination of the
      distribution of VGF mRNA in the adult rat central nervous system by using in situ
      hybridization. Robust expression was detected in many neurons throughout the
      brain and spinal cord, in several types of neurons in the retina, and in
      presumptive chromaffin cells of the adrenal medulla. In the brain, prominent
      expression of VGF mRNA was observed in neurons of the main and accessory
      olfactory bulbs; in the anterior olfactory nucleus; in the induseum griseum and
      taenia tecta; in the olfactory tubercle; in CA1-CA3, the hilus of the dentate
      gyrus, and the subicular complex of the hippocampal formation; in the piriform,
      periamygdaloid, transitional, and lateral entorhinal cortices; in the
      endopiriform nucleus; in the hypothalamus, particularly the preoptic,
      periventricular, supraoptic, suprachiasmatic, and arcuate nuclei; and in a number
      of septal, thalamic, amygdaloid, and brainstem nuclei. Labeling was also seen in
      neurons of the neocortex and transitional cortical areas, particularly in layer
      V, and in basal ganglia and cerebellum. These data demonstrate that VGF mRNA is
      expressed much more extensively in the brain than has been described in previous
      RNA or immunohistochemical studies, and, furthermore, that VGF is widely
      expressed in the spinal cord and retina.

PMID- 9550145
TI  - Rostral cerebellar malformation (rcm/rcm): a murine mutant to study
      regionalization of the cerebellum.
AB  - A recently described recessive mouse mutant, rostral cerebellar malformation
      (rcm/rcm), demonstrates a swaying gait at approximately 12 days of age (Lane et
      al. [1992] J. Hered. 83:315-318). The mutant cerebellar (Cb) phenotype consists
      of cerebellar tissue that extends rostrally, beyond the usual distinct anterior
      cerebellar boundary, into the midbrain (Lane et al. [1992] J. Hered. 83:315-318;
      Ackerman et al. [1997] Nature 386:838-842). Interestingly, the cerebellar ectopia
      occurs in the absence of any significant alterations in the distribution of
      nuclear groups within the brainstem. The ectopic Cb tissue is 1) adherent to the
      posterior and lateral aspects of the inferior colliculus and to the lateral
      aspect of the rostral brainstem and 2) contains acellular regions within the
      inner granular layer (igl) and ectopic, calbindin-immunoreactive Purkinje cells
      (PCs) deep to the igl. Within the Cb proper, PC organization, as revealed by
      zebrin II immunoreactivity, is generally normal. In the ectopic Cb tissue PCs
      also exhibit a banded zebrin distribution. Analysis of the spinocerebellar
      projection in the mutant suggests a lobular distribution similar to that seen in
      the normal mouse. Within the anterior region, however, the normal parasagittal
      banding pattern is somewhat obscured. Spinocerebellar innervation of the ectopic
      Cb tissue exists, but it is almost exclusively to the region adjacent to the
      caudal inferior colliculus. In conjunction with the recent finding that the
      mutation appears to affect a UNC-5-like receptor protein for netrin-1, a molecule
      that may be involved in axonal guidance and cell migration (Ackerman et al.
      [1997] Nature 386:838-842), our results suggest that this mutant is an important
      model for the analysis of cerebellar development and regionalization.

PMID- 9550146
TI  - In situ detection of H1-receptor mRNA and absence of apoptosis in the transient
      histamine system of the embryonic rat brain.
AB  - In the developing brain, histamine is one of the first neurotransmitters to
      appear. The concentration of histamine in the prenatal brain is fivefold that of
      adult levels. During the prenatal development a large transiently histamine
      immunoreactive cell population distinct from the adult histaminergic system can
      be found within a subpopulation of the developing serotonergic raphe nuclei
      neurons. Also histamine-immunoreactive nerve fibers are widely distributed
      already during the prenatal development extending to the diencephalon, the
      thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing
      mast cells also migrate into the brain during the late prenatal life. The wide
      distribution and high prenatal concentrations imply important functions for the
      histaminergic system during intrauterine development. However, little is known
      about the actual functions of histamine during development, and which of the
      histamine receptors are present in the prenatal rat brain is currently unknown.
      In the present study, we used in situ hybridization to study the distribution of
      H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could
      be detected in rat brain and in spinal cord on embryonic day (E) 14, and the
      expression pattern seemed to partially localize in areas containing histamine
      immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by
      reverse transcriptase polymerase chain reaction from embryonic brain samples and
      by Northern hybridization. The possible involvement of apoptosis in the
      disappearance of the developing transiently histaminergic system was studied by
      using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL)
      technique and with c-Fos immunostaining. Although histamine immunoreactivity
      disappears dramatically from the developing raphe nuclei after E18, only
      occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell
      bodies. The presence of H1R mRNA during the embryonic development renders it
      possible that histamine could exert an H1R-specific function at the time of the
      embryonic histamine peak.

PMID- 9550147
TI  - Localization of mRNA encoding the P2X2 receptor subunit of the adenosine 5'
      triphosphate-gated ion channel in the adult and developing rat inner ear by in
      situ hybridization.
AB  - Localization of expression of the adenosine 5'-triphosphate (ATP)-gated ion
      channel P2X2 receptor subunit (P2X2R) in the rat inner ear at different stages of
      development was achieved by using in situ mRNA hybridization. In the adult, P2X2R
      mRNA was strongly expressed in many of the cells bordering the cochlear
      endolymphatic compartment. This included the interdental cells of the spiral
      limbus, all cells of the inner sulcus and organ of Corti, and cells of the spiral
      prominence. In the vestibular labyrinth, strong expression was noted in the
      transitional cells at the base of the crista ampullaris and in the sensory
      epithelium of the crista and maculae. During development, P2X2R mRNA expression
      was evident in the precursors of these structures at the earliest period studied,
      embryonic day 12 (E12). Expression increased during the ontogeny in both the
      cochlear and the vestibular end organs. In addition, both the spiral and
      vestibular ganglia showed developmental expression. In contrast to the supporting
      cells of the organ of Corti, both inner and outer hair cells exhibited P2X2R mRNA
      only after postnatal day 10 (P10) through P12, concomitant with the onset of
      hearing. P2X2R expression levels in all cells fell from a maximum at P12-P18 to
      lower levels in the adult. In the adult, P2X2R mRNA levels were modest in outer
      hair cells in the basal (high-frequency) encoding region of the cochlea, and
      inner hair cell labeling was low throughout the cochlea. Reissner's membrane,
      which maintains an electrochemical barrier between scala vestibuli and scala
      media, showed considerable expression of P2X2R mRNA in early postnatal
      development, and expression was maintained at moderate levels in the adult
      cochlea. These data are consistent with a role for the P2X2R subunit in the
      processes of labyrinthine development and the regulation of the electrochemical
      gradients supporting auditory and vestibular sensory transduction.

PMID- 9550148
TI  - Early development of the peripheral nervous system in a lancelet species.
AB  - The developmental pattern of the lancelet (amphioxus) peripheral nervous system
      from embryos to larvae has been studied by using wholemount immunostaining and
      transmission electron microscopy. The peripheral nerves first appeared on the
      anterior dorsal surface of the medulla at the middle neurula stage, when the
      anterior nerve cord was just closing. A single axon with a large growth cone was
      the progenitor of each nerve. The nerve roots adopted an asymmetric arrangement
      soon after. The first nerve, likely a pair of pure sensory nerves, sprouted from
      the anterior tip of the nerve cord. This nerve may be comparable topographically
      to the preoptic nerve (the posterior branch of the terminal nerve) in lungfishes.
      However, the neuron that first extends its axon was located in the medulla, as in
      the other posterior nerves. One of the extramedullary primary sensory neurons,
      the corpuscles of de Quatrefages, appeared in larvae with the mouth and two
      anterior gill pores. Their axons were seemingly fasciculated with the efferent
      axon of the first nerve. The second nerve, the most complex one to appear during
      embryonic and early larval development, innervated the preoral pit and the buccal
      region. The third and fourth nerves on the left side also innervated the buccal
      region. The larval innervation patterns in the anterior region differed from the
      adult organization, suggesting a segmental rearrangement of the nerve supply
      during development. There was no evidence to dichotomize the peripheral nerves
      into cranial and spinal nerves, as exist in vertebrates. These characteristics of
      the peripheral nervous system in the lancelet indicate that this animal has a
      rather derived or primitive developmental system of peripheral nerves, making the
      analysis of homology with vertebrates difficult.

PMID- 9550149
TI  - ZENK protein regulation by song in the brain of songbirds.
AB  - When songbirds hear the song of another individual of the same species or when
      they sing, the mRNA levels of the ZENK gene increase rapidly in forebrain areas
      involved in vocal communication. This gene induction is thought to be related to
      long-term neuronal change and possibly the formation of song-related memories. We
      used immunocytochemistry to study the levels and distribution of ZENK protein in
      the brain of zebra finches and canaries after presentation of song playbacks.
      Birds that heard the playbacks and did not sing in response showed increased ZENK
      protein levels in auditory brain areas, including the caudomedial neostriatum and
      hyperstriatum ventrale, fields L1 and L3, the shelf adjacent to the high vocal
      center (HVC), the cup adjacent to the nucleus robustus archistriatalis (RA), and
      the nucleus mesencephalicus lateralis pars dorsalis (MLd). No ZENK expression was
      seen in song nuclei in these birds. Males that sang in response to the playbacks
      showed, in addition to auditory areas, increased ZENK protein in several song
      control nuclei, most prominently in HVC, RA, area X, and the dorsomedial nucleus
      (DN) of the intercollicular complex. The rise in ZENK protein followed that
      described previously for ZENK mRNA by a short lag, and the distribution of ZENK
      labeled cells was in agreement with previous analysis of mRNA distribution. Thus,
      ZENK protein regulation can be used to assess activation of brain areas involved
      in perceptual and motor aspects of song. Possible implications of ZENK induction
      in these areas are discussed.

PMID- 9550150
TI  - Circuitry and role of substance P-immunoreactive neurons in the primate retina.
AB  - In this paper, we extend our previous light microscopic (LM) study of substance P
      (SP)-containing amacrine and ganglion cell types of the human retina (Cuenca et
      al. [1995] J. Comp. Neurol. 356:491-504) to an electron microscopic (EM) and
      confocal-imaging study in order to reveal synaptic circuitry and putative input
      and output neurons. SP-immunoreactive (-IR) amacrine cells in primate retina are
      typically wide-field cells with large cell bodies occurring in normal or
      displaced positions relative to the inner plexiform layer (IPL). Their main
      dendrites bear many spines and are monostratified in stratum 3 (S3) of the IPL.
      Axon-like processes arise from dendrites close to the cell body and run for
      hundreds of microns at the same level as the dendrites, thus forming a relatively
      dense plexus in S3 of the IPL. SP-IR axon processes also climb to S1 to surround
      some amacrine cell bodies, and others pass into the outer plexiform layer (OPL).
      Still other axons run down to the ganglion cell layer, where they encircle SP-IR
      ganglion cells and pass on to end in the nerve fiber layer. The SP-IR ganglion
      cell types have large cell bodies (20-22 microm diameter) and dendrites that
      costratify in S3 among the SP-IR amacrine cell processes. Double immunostaining
      and study by confocal microscopy reveals that SP-IR amacrine cells in the monkey
      colocalize gamma-aminobutyric acid (GABA). Their main plexus of dendrites in S3
      of the IPL is skirted on the S2/S3 border by cone bipolar axons that stain for
      calbindin but intermingles primarily with glycinergic bipolar cell types of S3
      and S3-S4. Strongly GABA-IR/weakly glycine-IR amacrine cell bodies, in addition
      to the SP-IR large-bodied ganglion cell type, are targets of encircling SP-IR
      axon processes. EM study of the human SP-IR amacrine cell indicates that input
      synapses to its dendrites are from bipolar cell axons of the S2/S3 border, S3,
      and the S3/S4 border of the IPL neuropil (33% of the synaptic input) and from
      amacrine cell processes (67% of the synaptic input). The input amacrine cells are
      of at least two distinct types based on cytological criteria. Synaptic output
      from the SP-IR amacrine cell dendrites is to bipolar cell axons as reciprocal
      synapses (31%), to amacrine cells (40%), and to ganglion cell profiles, primarily
      in S3 (29%) of the IPL. The SP-IR axons synapse upon SP-IR ganglion cell bodies
      and axons, upon normally placed and displaced amacrine cell bodies, and upon
      bipolar cell dendrites in the OPL. In addition, they appear to synapse among
      themselves. We shall discuss a wiring diagram and the possible role of SP-IR
      amacrine cells in the primate retina.

PMID- 9550151
TI  - Spatial coding of odorant features in the glomerular layer of the rat olfactory
      bulb.
AB  - In order to determine whether molecular features of odorants are represented
      spatially in the glomerular layer of the olfactory bulb, we used metabolic
      mapping of [14C] 2-deoxyglucose uptake in rats exposed to equal vapor
      concentrations of odorants differing systematically in chemical structure. The
      odorants were ethyl acetate, ethyl butyrate, isoamyl acetate, and isoamyl
      butyrate. Statistical analysis of anatomically standardized arrays of uptake
      revealed that each ester produced a characteristic spatial pattern of activity in
      the glomerular layer. The patterns were similar in different rats exposed to the
      same odorant, and their complexity increased with increasing odorant carbon
      number. This finding suggests that the presence of more potentially recognized
      molecular features is associated with a greater number of activated receptors.
      Individual regions of the glomerular layer responded specifically to isoamyl
      esters, and other regions preferred ethyl esters. Regions of similar specificity
      occurred in lateral and medial aspects of the bulb, the medial representation
      being more caudal and ventral than the lateral one. This pattern correlates with
      projections of olfactory sensory neurons expressing the same putative olfactory
      receptor gene. The patterns overlapped greatly in the posterolateral and
      posteromedial glomerular layer, a finding one should predict, given the large
      overlap in chemical structure across the aliphatic esters. Thus, molecular
      features appear to be encoded spatially in the glomerular layer, and the identity
      of the odorant may be determined by a subsequent decoding of the combination of
      molecular features represented in the glomerular layer.

PMID- 9550152
TI  - Induction of cell division in olfactory basal epithelium following intranasal
      irrigation with wheat germ agglutinin-horseradish peroxidase.
AB  - The lectin, wheatgerm agglutinin (WGA) conjugated to horseradish peroxidase
      (HRP), previously was shown to be transported into the central nervous system
      following application by intranasal irrigation. The current study investigated
      the hypothesis that uptake of molecules, such as the lectin-conjugate, by
      olfactory receptor cells would mimic internalization of other substances
      including odorants. This process would result in both premature death of receptor
      cells and increased turnover of their precursors, globose basal cells.
      Tetramethylbenzidine histochemical analysis showed the presence of significant
      amounts of the lectin-conjugate in both the receptor epithelium and olfactory
      bulb until at least 2 weeks postintranasal application. Neither supporting nor
      globose basal cells contained WGA-HRP, suggesting that uptake was primarily into
      olfactory receptor cells. Cell turnover, assessed by tritiated-thymidine
      (thymidine) autoradiography, increased both 1 and 2 weeks, but not 3 and 4 weeks,
      following intranasal irrigation with WGA-HRP. Most of the cells containing
      thymidine labelling appeared to be globose basal cells, although supporting cells
      also occasionally exhibited labelling. Survival of either mature or immature
      receptor cells in the epithelium, indicated by epithelial thickness and cell
      density of the septal epithelium, also declined following treatment. These data
      suggest that uptake of substances may result in cell loss from the olfactory
      epithelium and increased mitotic activity of basal cells.

PMID- 9550153
TI  - Regulated spacing of synapses and presynaptic active zones at larval
      neuromuscular junctions in different genotypes of the flies Drosophila and
      Sarcophaga.
AB  - Synapses at larval neuromuscular junctions of the flies Drosophila melanogaster
      and Sarcophaga bullata are not distributed randomly. They have been studied in
      serial electron micrographs of two identified axons (axons 1 and 2) that
      innervate ventral longitudinal muscles 6 and 7 of the larval body wall. The
      following fly larvae were examined: axon 1--wild-type Sarcophaga and Drosophila
      and Drosophila mutants dunce(m14) and fasII(e76), a hypomorphic allele of the
      fasciclin II gene; and axon 2--drosophila wild-type, dunce(m14), and fasII(e76).
      These lines were selected to provide a wide range of nerve terminal phenotypes in
      which to study the distribution and spacing of synapses. Each terminal varicosity
      is applied closely to the underlying subsynaptic reticulum of the muscle fiber
      and has 15-40 synapses. Each synapse usually bears one or more active zones,
      characterized by dense bodies that are T-shaped in cross section; they are
      located at the presumed sites of transmitter release. The distribution of
      synapses was characterized from the center-to-center distance of each synapse to
      its nearest neighbor. The mean spacing between nearest-neighbor pairs ranged from
      0.84 microm to 1.05 microm for axon 1, showing no significant difference
      regardless of genotype. The corresponding values for axon 2, 0.58 microm to 0.75
      microm, were also statistically indistinguishable from one another in terminals
      of different genotype but differed significantly from the values for axon 1.
      Thus, the functional class of the axon provides a clear prediction of the spacing
      of its synapses, suggesting that spacing may be determined by the functional
      properties of transmission at the two types of terminals. Individual dense bodies
      were situated mostly at least 0.4 microm away from one another, suggesting that
      an interaction between neighboring active zones could prevent their final
      positions from being located more closely.

PMID- 9550154
TI  - Metabotropic glutamate receptor subtypes in axon terminals of projection fibers
      from the main and accessory olfactory bulbs: a light and electron microscopic
      immunohistochemical study in the rat.
AB  - Localization of metabotropic glutamate receptor subtypes, mGluR1, mGluR1alpha,
      mGluR2/3, mGluR4a, mGluR5, mGluR7a, mGluR7b, and mGluR8, was examined in some of
      the target areas of projection fibers from the main and accessory olfactory bulbs
      (MOB and AOB) by using subtype-specific antibodies. The superficial layer of the
      olfactory tubercle and layer Ia of the piriform cortex, the target areas of MOB,
      showed marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-like immunoreactivities (
      LI), and rather weak mGluR2/3-LI. The periamygdaloid cortical region including
      the target areas of both MOB and AOB showed intense mGluR2/3-LI as well as marked
      mGluR1-, mGluR5-, mGluR7a-, and mGluR8-LI. No significant mGluR1alpha-, mGluR4a-,
      or mGluR7b-LI was seen in these regions. After transection of the lateral
      olfactory tract, mGluR2/3-, mGluR7a-, and mGluR8-LI were reduced markedly in the
      target regions on the side ipsilateral to the transection; no significant changes
      were detected in mGluR1- or mGluR5-LI. Double labeling experiments indicated
      light and electron microscopically colocalization of mGluR7a- and mGluR8-LI in
      axon terminals on dendritic shafts of presumed interneurons in the superficial
      layer of the olfactory tubercle and layer Ia of the piriform cortex. Electron
      microscopically mGluR2/3-LI was seen in preterminal and terminal portions of
      axons, whereas mGluR7a- and mGluR8-LI were associated with presynaptic membrane
      specialization. Immunolabeled axon terminals were filled with round synaptic
      vesicles and constituted asymmetric synapses with dendritic profiles. The results
      suggest that glutamate release from axon terminals of projection fibers from MOB
      and AOB is regulated presynaptically and differentially through mGluR2/3,
      mGluR7a, and/or mGluR8.

PMID- 9550155
TI  - Visuotopic organisation and neuronal response selectivity for direction of motion
      in visual areas of the caudal temporal lobe of the marmoset monkey (Callithrix
      jacchus): middle temporal area, middle temporal crescent, and surrounding cortex.
AB  - On the basis of extracellular recordings in marmoset monkeys, we report on the
      organisation of the middle temporal area (MT) and the surrounding middle temporal
      crescent (MTc). Area MT is approximately 5-mm long and 2-mm wide, whereas the MTc
      forms a crescent-shaped band of cortex 1-mm wide. Neurones in area MT form a
      first-order representation of the contralateral hemifield, whereas those in the
      MTc form a second-order representation with a field discontinuity near the
      horizontal meridian. The representation of the vertical meridian forms the border
      between area MT and the MTc. In both areas, the fovea is represented
      ventrocaudally, and the visual field periphery is represented dorsorostrally.
      Analysis of single units revealed that 86% of cells in area MT show a strong
      selectivity for the direction of motion of visual stimuli. The proportion of
      direction-selective cells in the MTc (53%), whereas lower than that in area MT,
      is much higher than that observed in most other visual areas. Neurones in the
      cortex immediately rostral to area MT and the MTc are direction selective, with
      receptive fields predominantly located in the visual field periphery. In
      contrast, only a minority of the cells in the cortex ventral to the MTc are
      direction selective, and their receptive fields emphasise central vision. The
      results suggest that the MTc is functionally closely related to area MT, and
      distinct from the areas forming the dorsolateral complex. The MTc may have a role
      in combining information about motion in the visual field, processed by area MT,
      with information about stimulus shape, processed by the dorsolateral complex.

PMID- 9550156
TI  - Association of ecto-5'-nucleotidase with specific cell types in the adult and
      developing rat olfactory organ.
AB  - A unique feature of the olfactory epithelium is its ability to give rise to new
      sensory neurons throughout life and also following injury. Cells at the basal
      side of the epithelium serve as neurogenic progenitor cells. The enzyme ecto-5'
      nucleotidase is expressed at the surface of developing nerve cells and is
      regarded as a marker of neural development. To study the expression pattern of
      the enzyme, we analyzed its distribution in the adult and developing rat
      olfactory organ. Labeling is restricted to specific cell types and varies between
      the epithelia investigated. At the basal side of the olfactory epithelium,
      activity of 5'-nucleotidase is associated specifically with the dark/horizontal
      basal cells. Neither the light/globose basal cells, which are the immediate
      precursors of the sensory receptor cells, nor subsets of potentially immature
      olfactory receptor cells are labeled. On the other hand, microvillar cells
      dispersed at the lumenal side of the epithelium contain 5'-nucleotidase activity.
      The enzyme is also present at the inner lining of the ducts of Bowman's glands as
      they traverse the epithelium. Within the respiratory epithelium, activity of 5'
      nucleotidase is associated with basal cells as well as with the epithelial
      surface. During development, 5'-nucleotidase is initially limited to the
      respiratory epithelium, including its basal cells. Dark/horizontal basal cells of
      the olfactory epithelium, which are positive for 5'-nucleotidase, first appear at
      the border of the respiratory epithelium, suggesting that they might originate
      from immigrating basal cells of the respiratory epithelium. Within the
      vomeronasal organ, labeling is largely restricted to the receptor-free
      epithelium. Although the functional role of 5'-nucleotidase in the olfactory
      system needs to be further defined, the distribution of the enzyme can be used
      successfully as a marker for defined cell types.

PMID- 9550157
TI  - Deciphering dietary reference intakes.

PMID- 9550158
TI  - ADA urges changes to HCFA's hospital Medicare rules.

PMID- 9550159
TI  - When food becomes a cry for help. How dietitians can combat childhood eating
      disorders. Interview by Nancy I Hahn.

PMID- 9550160
TI  - Young children and dietary fat intake: how much is too little?

PMID- 9550161
TI  - Are we making decisions based on evidence?

PMID- 9550163
TI  - Weight training increases fat-free mass and strength in untrained young women.
AB  - OBJECTIVE: To examine the effects of a weight training program on the resting
      metabolic rate, fat-free mass, strength, and dietary intake of untrained young
      women. DESIGN: A 12-week weight training program was completed by 20 previously
      untrained women aged 19 through 44 years. SUBJECTS: Twenty-three study subjects
      and 14 control subjects were recruited on a volunteer basis. Twenty study
      subjects and 10 control subjects completed the study. INTERVENTIONS: Study
      subjects participated in a 12-week moderate-intensity, progressive resistance
      weight training program consisting of 2 supervised sessions per week with 6 types
      of lifting exercises per session. Resting metabolic rate, fat-free mass,
      strength, and dietary intake were measured before and immediately after the
      study. STATISTICAL ANALYSES: Repeated measures analysis of variance and t tests
      (unequal variance and paired) were used to determine interaction effects and
      differences within and between groups. RESULTS: The study group increased their
      fat-free mass (mean+/-standard deviation) from 44.2+/-5.4 kg to 46.2+/-6.0 kg
      (P<.001). Elbow flexion, elbow extension, and knee flexion strength all increased
      from 28.9+/-5.3 to 34.5+/-3.8, 16.9+/-4.9 to 22.1+/-5.3, and 39.5+/-8.6 to 48.6+/
      7.3 ft-lb, respectively (P<.001). Percent body fat decreased from 29.8+/-2.8 to
      27.2+/-2.6 (P<.001) without a significant change in body weight. Resting
      metabolic rate did not change significantly (P>.05). APPLICATION: A moderate
      intensity weight training program increased strength and fat-free mass and
      decreased body fat in normal-weight young women. Favorable changes in body
      composition were obtained without restricting food intake. The increase in fat
      free mass did not increase resting metabolic rate significantly.

PMID- 9550162
TI  - Persons successful at long-term weight loss and maintenance continue to consume a
      low-energy, low-fat diet.
AB  - OBJECTIVES: To describe the dietary intakes of persons who successfully
      maintained weight loss and to determine if differences exist between those who
      lost weight on their own vs those who received assistance with weight loss (eg,
      participated in a commercial or self-help program or were seen individually by a
      dietitian). Intakes of selected nutrients were also compared with data from the
      third National Health and Nutrition Examination Survey (NHANES III) and the 1989
      Recommended Dietary Allowances (RDAs). SUBJECTS: Subjects were 355 women and 83
      men, aged 18 years or older, primarily white, who had maintained a weight loss of
      at least 13.6 kg for at least 1 year, and were the initial enrollees in the
      ongoing National Weight Control Registry. On average, the participants had lost
      30 kg and maintained the weight loss for 5.1 years. METHODS: A cross-sectional
      study in which subjects in the registry completed demographic and weight history
      questionnaires as well as the Health Habits and History Questionnaire developed
      by Block et al. Subjects' dietary intake data were compared with that of
      similarly aged men and women in the NHANES III cohort and to the RDAs. Adequacy
      of the diet was assessed by comparing the intake of selected nutrients (iron;
      calcium; and vitamins C, A, and E) in subjects who lost weight on their own or
      with assistance. RESULTS: Successful maintainers of weight loss reported
      continued consumption of a low-energy and low-fat diet. Women in the registry
      reported eating an average of 1,306 kcal/day (24.3% of energy from fat); men
      reported consuming 1,685 kcal (23.5% of energy from fat). Subjects in the
      registry reported consuming less energy and a lower percentage of energy from fat
      than NHANES III subjects did. Subjects who lost weight on their own did not
      differ from those who lost weight with assistance in regards to energy intake,
      percent of energy from fat, or intake of selected nutrients (iron; calcium; and
      vitamins C, A, and E). In addition, subjects who lost weight on their own and
      those who lost weight with assistance met the RDAs for calcium and vitamins C, A,
      and E for persons aged 25 years or older. APPLICATIONS: Because continued
      consumption of a low-fat, low-energy diet may be necessary for long-term weight
      control, persons who have successfully lost weight should be encouraged to
      maintain such a diet.

PMID- 9550164
TI  - Practice points: translating research into practice. Fueling their engines for
      the long haul: teaching good nutrition to young athletes.

PMID- 9550165
TI  - Nutritional status of female athletes with subclinical eating disorders.
AB  - OBJECTIVE: To assess the energy and nutritional status of female athletes with
      subclinical eating disorders and compare them with that of control subjects and
      standard norms. DESIGN: Group classification (subclinical eating disorder or
      control) was based on responses to a health and diet history questionnaire, a
      battery of self-report eating disorder questionnaires, and an in-depth interview.
      Energy and nutrient intakes and energy expenditure were determined by means of 7
      day weighed food records and 7-day activity logs. Micronutrient status was
      assessed for iron, zinc, magnesium, vitamin B-12, and folate. SUBJECTS: Twenty
      four female athletes with subclinical eating disorders and 24 female control
      athletes. STATISTICAL ANALYSES: Descriptive statistics were used to analyze
      demographic data. One-way analysis of variance was used to determine group
      differences in energy and nutrient intakes, energy balance, and blood values.
      RESULTS: Groups were similar in age, height, weight, fat-free mass, and body mass
      index. Mean energy intake was lower in the group with subclinical eating
      disorders (1,989 kcal/day) than in the control group (2,300 kcal/day; P=.004),
      whereas mean energy expenditures were similar (2,405 and 2,293 kcal/day,
      respectively). The group with subclinical eating disorders had significantly
      (P<.05) lower mean protein and fat intakes compared with the control group; mean
      micronutrient intakes were not significantly different. Mean status measures for
      iron, zinc, magnesium, vitamin B-12, and folate were within the normal ranges for
      both groups and no differences were noted between the groups. A similar number of
      athletes within each group used vitamin/mineral supplements < or = 4 times per
      week. CONCLUSION: Although female athletes with subclinical eating disorders had
      dietary intakes of energy, protein, carbohydrate, and certain micronutrients that
      were below recommended levels, micronutrient status appeared relatively
      unaffected, probably due to their use of supplements.

PMID- 9550166
TI  - Assessment of energy intake underreporting by doubly labeled water and
      observations on reported nutrient intakes in children.
AB  - OBJECTIVE: To compare reported energy intake with energy expenditure using doubly
      labeled water (DLW). Additionally, we compared reported nutrient intakes of our
      subject population with national survey population data from the third National
      Health and Nutrition Examination Survey (NHANES III). DESIGN: This was a cross
      sectional study of children, balanced by race and gender, primarily characterized
      by 4 body types: lean, obese, centrally fat, or peripherally fat.
      SUBJECTS/SETTING: Children (n=118; mean age=10 years) kept 8-day food records,
      with nutritionists recording weekday school lunch intakes. These subjects,
      assisted by their parents, recorded all breakfasts, dinners, snacks, and weekend
      lunches. STATISTICAL ANALYSES PERFORMED: Data were analyzed using least squares
      analysis of variance with the general linear models procedure. Tukey's test was
      used for multiple comparisons of predicted treatment means. RESULTS: Mean daily
      energy intake was underreported by 17% to 33% of energy expenditure. The tendency
      to underreport increased with age. Underreporting occurred in all groups and
      subgroups studied. Reported mean intakes of vitamin A, vitamin E, vitamin B-6,
      calcium, zinc, and copper were less than 70% of the Recommended Dietary Allowance
      (RDA) for African-American girls, whereas African-American boys reported
      similarly low intakes of copper. On average, white girls reported intakes less
      than 70% of the RDA for zinc and copper, whereas white boys reported low intakes
      of copper (60% of the RDA). Reported intakes in general were somewhat lower than
      those reported in NHANES III. APPLICATIONS/CONCLUSIONS: Dietetics professionals
      may modify the nutritional advice they give to patients/subjects based on food
      intake records and other data. For children, particularly, it is imperative that
      ethnic and gender differences be taken into consideration and that all foods
      eaten be accounted for as much as possible.

PMID- 9550167
TI  - A randomized controlled trial evaluating nutrition counseling with or without
      oral supplementation in malnourished HIV-infected patients.
AB  - OBJECTIVE: To evaluate the effects of nutrition counseling with or without oral
      supplementation in malnourished patients infected with the human immunodeficiency
      virus (HIV). DESIGN: Randomized controlled trial. SUBJECTS: HIV-infected men
      (n=118) who were less than 90% of usual weight for height or who had lost more
      than 10% of body weight. INTERVENTION: Nutrition counseling alone (control group)
      vs nutrition counseling plus enteral supplementation (supplement group) for 6
      weeks. All patients were instructed to consume a diet that exceeded estimated
      total energy expenditure by 960 kcal/day. MAIN OUTCOME MEASURES: Weight, skinfold
      thickness, fat-free mass, grip strength, quality of life, and cognitive function
      (Buschke test). STATISTICAL ANALYSES: Differences in baseline variables and
      outcomes were evaluated using analysis of variance or the Wilcoxon rank sum test.
      RESULTS: Ninety-nine men completed at least 4 weeks of treatment, 49 in the
      supplement group and 50 in the control group. Half the patients in each treatment
      group achieved at least 80% of their energy target. No differences in weight,
      skinfold thickness measurements, or quality of life were observed. Compared with
      the control group, the supplement group had larger increases in fat-free mass and
      grip strength, although the differences did not reach statistical significance.
      APPLICATIONS: In the short term, nutrition counseling with or without oral
      supplementation can achieve a substantial increase in energy intake in about 50%
      of malnourished HIV-infected patients. Although further study is needed to
      evaluate long-term effects, these findings suggest that nutrition counseling has
      an important role in the management of malnourished HIV-infected patients.

PMID- 9550168
TI  - The Harris-Benedict studies of human basal metabolism: history and limitations.
AB  - In the early part of the 20th century, numerous studies of human basal metabolism
      were conducted at the Nutrition Laboratory of the Carnegie Institution of
      Washington in Boston, Mass, under the direction of Francis G. Benedict.
      Prediction equations for basal energy expenditure (BEE) were developed from these
      studies. The expressed purpose of these equations was to establish normal
      standards to serve as a benchmark for comparison with BEE of persons with various
      disease states such as diabetes, thyroid, and other febrile diseases. The Harris
      Benedict equations remain the most common method for calculating BEE for clinical
      and research purposes. The widespread use of the equations and the relative
      inaccessibility of the original work highlights the importance of reviewing the
      data from which the standards were developed. A review of the data reveals that
      the methods and conclusions of Harris and Benedict appear valid and reasonable,
      albeit not error free. All of the variables used in the equations have sound
      physiologic basis for use in predicting BEE. Supplemental data from the Nutrition
      Laboratory indicates that the original equations can be applied over a wide range
      of age and body types. The commonly held assumption that the Harris-Benedict
      equations overestimate BEE in obese persons may not be true for persons who are
      moderately obese.

PMID- 9550169
TI  - Dieting and binge eating among adolescents: what do they really mean?
AB  - The study objectives were to gain insight into how the terms "dieting" and "binge
      eating" are understood and used by adolescents and to assess whether
      interpretations of these terms are consistent across age and gender. Twenty-five
      focus groups were conducted with 203 adolescents (138 girls and 65 boys) in urban
      public junior and senior high schools. Respondents were asked questions about
      dieting and binge eating behaviors. In the majority of groups (n=19), healthful
      eating behaviors, such as eating less fat or more fruits and vegetables, were
      mentioned in reference to dieting. However, in many of the groups (n=13)
      unhealthful eating behaviors, such as skipping meals or "starvation," were also
      described. Dieting was frequently described as an umbrella term for different
      behaviors aimed at weight control (ie, physical activity) or in nonbehavioral
      terms (ie, as a desire or plan for weight loss). Although binge eating was
      described as overeating by many participants, often it was not clear if youth
      were referring to uncontrolled overeating. In nearly half of the groups,
      participants indicated unfamiliarity with the term "binge eating." There was some
      confusion between binge eating and other forms of disordered eating. The findings
      suggest that prevalence rates of self-reported dieting and binge eating behaviors
      should be interpreted with caution and it should not be assumed that the majority
      of adolescents who self-report dieting are engaging in unhealthful behaviors. In
      providing nutrition counseling to youth, and in assessing dieting and binge
      eating behaviors in clinical settings and in research studies, specific behaviors
      should be defined.

PMID- 9550170
TI  - A model for making outcomes research standard practice in clinical dietetics.
AB  - In today's rapidly changing health care environment, it is imperative that
      dietitians demonstrate the importance of their role as health care providers by
      initiating and participating in outcomes research. Patient care should be based
      on empirical studies, and clinical dietitians should participate in or be at the
      helm of such investigations. Nutrition research is usually accomplished and
      reported by persons with MD or PhD degrees who do not have clinical training in
      nutrition and does not often address situations encountered by dietitians in
      clinical settings. This article examines the extent to which clinical dietitians
      are conducting and reporting outcomes research, their attitudes about such
      research, and how they think they could best acquire the skills needed to
      incorporate outcomes research into their practice. Results indicate that clinical
      dietitians are not writing a substantial percentage of articles and that reports
      of outcomes research are not commonly included in clinical nutrition journals.
      Clinical dietitians appear to value the inclusion of research in clinical
      practice, but they are not spending a great amount of time doing research.
      Dietitians report being comfortable about participating in research but not about
      designing, conducting, and reporting research. Results from several surveys were
      used to develop a model for integrating research in clinical practice. This model
      includes the research process as a basis for clinical practice. A model for
      collaborative efforts between clinical and academic dietitians is also proposed
      and emphasizes the responsibility of academic dietetics training programs in the
      integration of research and clinical practice.

PMID- 9550171
TI  - Variation in perceptions of a medium' food portion: implications for dietary
      guidance.

PMID- 9550172
TI  - An elemental diet containing medium-chain triglycerides and enzymatically
      hydrolyzed protein can improve gastrointestinal tolerance in people infected with
      HIV.

PMID- 9550173
TI  - Position of The American Dietetic Association: fat replacers.

PMID- 9550174
TI  - President's page: Food security--take your place at the advocates' table.

PMID- 9550175
TI  - A brief history of Doppler ultrasound in the diagnosis of peripheral vascular
      disease.
AB  - The history of Doppler ultrasound in peripheral vascular diagnosis is considered
      in terms of basic developments, clinical applications and impact on medical
      practice. Many early developments occurred at Osaka University in Japan and the
      University of Washington in the United States. Through progressive steps, Doppler
      ultrasound technology has provided clinical applications in blood-flow sensing,
      waveform analysis, localizing blood flow and two-dimensional (2-D) mapping of
      blood flow. An important advance was the development of duplex and color Doppler
      scanning. Real time velocity measurements and flow mapping have led to many
      clinical applications. Two important applications have been detection and grading
      of atherosclerotic plaques in the internal carotid artery and the diagnosis of
      deep venous thrombosis. Doppler ultrasound is the preferred noninvasive imaging
      method for each of these clinical problems. The recent reaffirmation of carotid
      endarterectomy as the appropriate management for certain categories of carotid
      atherosclerotic occlusive disease has led to guidelines for selecting patients
      for carotid endarterectomy. New Doppler ultrasound criteria are being developed
      to identify categories of stenosis that relate to these guidelines. The
      establishment of Doppler ultrasound has led to training programs for
      technologists and physicians, certification of technologists and establishment of
      standards and quality control measures for vascular laboratories.

PMID- 9550176
TI  - Color Doppler imaging of the myocardium: current status and potential clinical
      applications.
AB  - Doppler myocardial imaging (DMI) is a new technique with potential clinical and
      research applications. It applies traditional pulsed and color Doppler techniques
      to the analysis of myocardial contractile velocity. A major area of focus is in
      the quantitation of regional and global myocardial function and evaluation of
      myocardial perfusion in conjunction with myocardial contrast studies. DMI may
      also provide a direct, relatively load-independent assessment of diastolic
      function. Further work is required to identify its role in clinical and research
      studies.

PMID- 9550177
TI  - Ultrasonic tissue characterization for coronary care unit patients with acute
      myocardial infarction.
AB  - The ultrasonic integrated backscatter of myocardium changes in infarction and
      ischemia. On the third day after acute myocardial infarction, 30 patients
      underwent ultrasonic tissue characterization from the parasternal short-axis
      view. With a composite parameter, the phase-weighted variation, sensitivity,
      specificity, and accuracy for diagnosing multivessel coronary artery disease were
      84.6%, 52.9% and 66.6%, respectively. Using 67 degrees as the cutoff value for
      the phase deviation of the backscatter power curve, the recanalization of the
      infarct-related artery could be detected with a positive predictive value of
      77.7% and a negative predictive value of 66.6%. Ultrasonic tissue
      characterization is a feasible technique for detecting the multivessel coronary
      artery diseases and the recanalization of infarct-related artery for patients
      with acute myocardial infarction. The diminished cardiac cycle-dependent
      variation in integrated backscatter and increased phase deviation can
      differentiate patent coronary arteries from those coronary arteries with
      anatomically significant stenoses.

PMID- 9550178
TI  - Fetal biometry and outcome in monochorionic vs. dichorionic twin pregnancies; a
      retrospective cross-sectional matched-control study.
AB  - Fetal biometry, amniotic fluid volume distribution and perinatal outcome were
      determined in a retrospective, cross-sectional matched-control study design,
      including 20 monochorionic (MC) twin pregnancies and 20 dichorionic (DC) twin
      pregnancies (historic controls). Intertwin differences for fetal abdominal
      circumference were larger in the MC subset than in the DC subset. Fetofetal
      transfusion syndrome, based upon a combination of oligohydramnios in one sac and
      polyhydramnios in the other sac, existed in 40% (8 of 20) of the MC twin
      pregnancies, but in none of the DC twin pregnancies. Mean gestational age at
      delivery was significantly shorter in the MC subset (30.9 weeks) than in the DC
      subset (34.3 weeks). The perinatal death rate was significantly higher in MC twin
      pregnancies (50%) than in DC twin pregnancies (15%). No differences were
      established for intertwin weight estimates by ultrasound and birth weight between
      both subsets. The poor perinatal outcome in monochorionicity is mainly a result
      of the degree of premature delivery.

PMID- 9550179
TI  - Blood flow imaging and volume flow quantitation with intravascular ultrasound.
AB  - Current intravascular ultrasound techniques produce real-time imaging of a vessel
      cross-section with a scan plane approximately normal to blood flow. When a
      cluster of randomly distributed blood particles moves across the ultrasound beam,
      the received echo signals decorrelate as a function of time. This phenomenon may
      be used to estimate blood velocities by measuring the decorrelation rate from a
      sequence of blood scattering signals. A decorrelation-based method for measuring
      local blood velocity and quantifying volume flow from cross-sectional radio
      frequency intravascular echo signals was developed. Serial in vitro measurements
      were performed with a flow phantom to test the principle of the proposed velocity
      estimation method. An in vivo pig experiment was carried out to study the
      feasibility of applying this method in clinical settings. Preliminary results of
      this study indicate that the proposed decorrelation method is able to extract
      cross-sectional velocity data and volumetric flow both in vitro and in vivo.

PMID- 9550180
TI  - An in vivo method for measuring the mechanical properties of the skin using
      ultrasound.
AB  - In this study, we report a new and original device called the "echorheometer,"
      comprising a suction system with an ultrasound scanner (A-mode, TM-mode and B
      mode) that enables the simultaneous visualization and measurement of the
      deformation of skin structures in vivo. With the scanner described here, high
      resolution is obtained using a strongly focused, wide-band 20-MHz center
      frequency transducer, with an axial resolution of 0.07 mm. This device can
      determine, noninvasively, not only those skin structures that are involved in the
      deformation, but also their morphological variation and their extent of
      involvement with the degree of stress applied. Using this device, the behavior of
      the dermis and subcutaneous fat, while under suction, was investigated on the
      volar forearm of 10 volunteers. The results showed that the resistance to the
      applied vertical stress is essentially due to the dermis rather than the
      subcutaneous fat, and that there is a certain amount of infiltration of fluid
      into the tissues under suction. In addition, it was shown that the dermal
      response to an applied suction is initially due to its own natural tension and
      that, with increasing deformation, the intrinsic dermal elasticity has a greater
      contribution to the resistance of stress. With this information, we hope to
      develop a mechanical model to define appropriate mechanical parameters for skin.
      This will allow the evaluation of changes in the dermis and also enable
      therapeutic intervention to be assessed. Furthermore, it could also be applied to
      studies of skin ageing and the assessment of cosmetic product efficacy
      (emolliency, hydratation, etc.).

PMID- 9550181
TI  - Quantification of sonographic echogenicity with grey-level histogram width: a
      clinical tissue characterization.
AB  - Grey-level histogram width (GLHW) values obtained by common sonographic devices
      were large in echogenic image and small in less echoic parts. The Aloka UIP-100
      computer system, SSD-680, and Toshiba SSA-270A sonographs showed GLHW values not
      significantly different when tested with RMI-412 phantom with the device contrast
      set at the lowest level. No influence on the GLHW value was observed by the
      changes of device gain, STC or image depth in the range of clinical practice.
      Device contrast control influenced the value. Although two sonographs showed
      significant differences from UIP-100, they were easily corrected by a small
      factor. Normal ranges of GLHW values of the placenta were obtained every 2 weeks,
      from 20 to 41 weeks, in 222 normal pregnancies measured by old scanners. GLHW
      values of normal pregnancies measured by the new Aloka and Toshiba machines were
      distributed within the normal ranges, and those of Grannum Grade III abnormally
      echogenic placenta were greater than the upper normal range. GLHW is a
      reproducible value among commercial ultrasonic devices, and the value is useful
      in clinical practice. Manual and automated GLHW values were identical.

PMID- 9550182
TI  - In vitro investigation of lymph node metastasis of colorectal cancer using
      ultrasonic spectral parameters.
AB  - Lymph node involvement is one of the major factors affecting the prognosis of
      colorectal cancer. Various imaging methods, including ultrasound and computed
      tomography, are not sufficiently sensitive or specific for reliably determining
      lymph node involvement. We investigated the feasibility of using ultrasonic
      tissue characterization (UTC) based on spectrum analysis of backscattered echo
      signals for diagnosing lymph node metastasis of colorectal cancer in vitro. Forty
      lymph nodes, including 17 metastatic and 23 nonmetastatic nodes, from 11
      colorectal cancer operations were investigated. Lymph nodes were scanned using a
      clinical instrument; B-mode imaging was performed for each lymph node, and
      radiofrequency (RF) data were acquired. The UTC parameters, slope and intercept,
      were calculated from the normalized power spectrum of the backscattered echo
      signals from each lymph node. The mean values of UTC parameters of metastatic and
      nonmetastatic lymph nodes were compared. The accuracy of UTC in distinguishing
      metastatic from nonmetastatic lymph nodes was calculated using discriminant
      analysis. Receiver operating characteristic (ROC) analysis was performed to
      compare the classification efficacy of UTC and B-mode ultrasound. UTC parameters
      demonstrated a significant difference in parameter values between metastatic and
      nonmetastatic lymph nodes. The overall accuracy in diagnosing the lymph node
      metastasis was 87.5% for UTC and 77.5% for B-mode ultrasound. ROC analysis
      produced an ROC curve area of 0.92 or 0.89 for UTC (depending on the performance
      assessment algorithm) and 0.84 for B-mode ultrasound, which indicated that UTC
      performed markedly better than B-mode ultrasound in diagnosing metastatic lymph
      nodes. The advantages of UTC over conventional B-mode ultrasound in
      discriminating metastatic lymph nodes from nonmetastatic lymph nodes are
      extremely encouraging, and warrant an in vivo UTC study.

PMID- 9550183
TI  - Kinetics of the "black hole" phenomenon in ultrasound backscattering measurements
      with red blood cell aggregation.
AB  - The observation of a hypoechoic zone around the center of large tubes (the "black
      hole" phenomenon) in ultrasound backscattering measurements with red blood cell
      (RBC) aggregation was reported for the first time in 1989. Since then, a very
      limited number of studies tried to explain its complex mechanisms. In this study,
      blood models characterized by different RBC aggregation levels were prepared by
      diluting horse blood plasma with a saline solution in different proportions. A
      laser reflectometry technique was used to characterize the RBC aggregation
      kinetics and cohesion forces between RBCs for each blood sample. The blood was
      circulated in a 12.7 mm diameter vertical tube. For each experimental flow
      condition tested, 25 or 15 power Doppler ultrasound measurements were performed
      across the tube with a 10-MHz system and insonation angles varying between 40
      degrees to 70 degrees. For flow rates varying between 100 and 1250 mL/min, the
      "black hole" was observed in most measurements performed with different
      aggregating RBC models. The "black hole" was more pronounced for RBCs with a high
      kinetics of aggregation and measurements with increasing Doppler angles. Previous
      studies suggested that this phenomenon is due to tube entrance effects, and the
      reduction of RBC aggregation at very low shear rates around the center of the
      tube. In the present study, the "black hole" was observed for shear rates up to
      25 s(-1). It is suggested that the structural organization and orientation of RBC
      rouleaux may participate in the mechanism leading to the "black hole" phenomenon.
      A schematic representation of the rheological behavior of horse RBCs in a large
      tube under steady flow is presented.

PMID- 9550184
TI  - Experimental study of stability of a contrast agent in an ultrasound field.
AB  - Attenuation coefficient and phase velocity measurements and direct optical
      observations showed that microbubbles of a contrast agent (Albunex) in 5% bovine
      albumin solution were not stable under ultrasonic irradiation. When the
      concentration of Albunex was 0.41 microL/mL and a 2.5-MHz phased array transducer
      of a Hewlett-Packard ultrasound imaging system (Model 77020AC) was used as the
      ultrasound source (the compression and rarefaction peak pressure amplitudes were,
      respectively, equal to 2 MPa and 1 MPa, the repetition frequency was 2.64 kHz),
      the attenuation coefficient at 2.5 MHz dropped from 40 dB/cm to 16 dB/cm after 2
      min of continuous insonification. Under a static condition, it was shown by
      direct optical observations that the microbubbles shrank and aggregated to form
      clusters or were destroyed under insonification; pressure amplitude was estimated
      to be 0.5 MPa, frequency = 2.44 MHz, and the pulse repetition frequency was 5
      kHz.

PMID- 9550185
TI  - Temperature rise generated by ultrasound in the presence of contrast agent.
AB  - Temperature elevation vs. time generated by a focused Gausssian ultrasound beam
      in the presence of contrast agents has been calculated using a perfect absorbing
      disc model. The results suggest that, if the contrast agent (Albunex) is
      introduced into the body intravenously, the temperature rise in the heart, which
      is 4.5 cm from the transducer, generated by 110-mW (the corresponding acoustic
      intensity at the transducer front surface is 0.4 W/cm2) 2-MHz ultrasound is about
      2 degrees C in 10 s. The relationship between temperature rise and the blood
      perfusion, acoustic power and focal length is discussed.

PMID- 9550186
TI  - Demonstration of potential noninvasive ultrasound brain therapy through an intact
      skull.
AB  - Utilization of therapeutic ultrasound in the brain has been seriously limited by
      the commonly accepted view that these exposures would require that a piece of the
      skull bone be removed to allow the ultrasound beam to propagate into the brain.
      In this paper, the feasibility of delivering ultrasound therapy through the
      intact skull was studied. Sonications were performed through a piece of human
      skull with focused transducers at 0.248, 0.559, 1.0 and 1.68 MHz. The skull
      attenuated and distorted the field; however, a sharp focal spot was created at
      frequencies of 1 MHz or lower. At the higher frequency, the focus was destroyed.
      To investigate the feasibility of compensating for the ultrasound field
      distortion caused by the bone, phased array experiments were performed. Two
      arrays with 64 elements, operating at 0.6 MHz and 1.58 MHz, were used in these
      experiments. The phase shifts caused by the skull were measured for each element
      of the arrays and then compensated for by phase-control circuitry. These phase
      corrections allowed a sharp focus to be generated at both frequencies. Finally,
      tissue destruction was induced by using pulsed sonication through a piece of
      human skull in a rabbit brain in vivo at the frequency of 0.559 MHz. In summary,
      the results showed that transcranial delivery of therapeutic ultrasound into the
      brain may be feasible.

PMID- 9550187
TI  - Enhancement of ultrasonically-induced hemolysis by perfluorocarbon-based compared
      to air-based echo-contrast agents.
AB  - Hemolysis induced by ultrasonic activation of various contrast-agent gas bodies
      was investigated. Canine whole blood, with high concentrations of the agents held
      in 1 mm thick chambers, was exposed in the nearfield of a 2.4-MHz ultrasound beam
      in a 37 degrees C water bath. Sterile phosphate buffered saline (PBS) served as a
      control agent without gas bodies. Albunex (Mallinckrodt Medical, St. Louis, MO)
      and Levovist (Schering AG, Berlin, Germany) represented the air-based contrast
      agents. The experimental agents FS069 (Optison, Molecular Biosystems Inc., San
      Diego, CA) and modified MRX-130 (ImaRx Pharmaceutical Corp., Tucson, AZ)
      represented perfluorocarbon-based contrast agents. No significant ultrasonically
      induced hemolysis was detected for the PBS or Levovist suspensions. After 1 s
      continuous exposure, ultrasonically-induced hemolysis was significant for Albunex
      at 0.4 MPa or higher pressure amplitudes, for FS069 at 0.2 MPa and for modified
      MRX-130 at 0.4 MPa. Hemolysis found after pulsed exposure with 10 micros pulses
      and 1 ms pulse repetition period was significant for Albunex, FS069 and modified
      MRX-130 above thresholds of 1.1 MPa, 0.57 MPa and 1.6 MPa, respectively. FS069
      led to more hemolysis after pulsed mode exposures of 1 s duration or longer than
      did Albunex. Reduced concentrations of gas bodies gave increased thresholds and
      reduced hemolysis. These results indicate that improvements in persistence of
      contrast agents, which increase their clinical utility, may also enhance the
      potential for cavitational bioeffects.

PMID- 9550188
TI  - In vivo pressure measurements of lithotripsy shock waves in pigs.
AB  - Stone comminution and tissue damage in lithotripsy are sensitive to the acoustic
      field within the kidney, yet knowledge of shock waves in vivo is limited. We have
      made measurements of lithotripsy shock waves inside pigs with small hydrophones
      constructed of a 25-microm PVDF membrane stretched over a 21-mm diameter ring. A
      thin layer of silicone rubber was used to isolate the membrane electrically from
      pig fluid. A hydrophone was positioned around the pig kidney following a flank
      incision. Hydrophones were placed on either the anterior (shock wave entrance) or
      the posterior (shock wave exit) surface of the left kidney. Fluoroscopic imaging
      was used to orient the hydrophone perpendicular to the shock wave. For each pig,
      the voltage settings (12-24 kV) and the position of the shock wave focus within
      the kidney were varied. Waveforms measured within the pig had a shape very
      similar to those measured in water, but the peak pressure was about 70% of that
      in water. The focal region in vivo was 82 mm x 20 mm, larger than that measured
      in vitro (57 mm x 12 mm). It appeared that a combination of nonlinear effects and
      inhomogeneities in the tissue broadened the focus of the lithotripter. The shock
      rise time was on the order of 100 ns, substantially more than the rise time
      measured in water, and was attributed to higher absorption in tissue.

PMID- 9550189
TI  - Subspecies of protein kinase C in the rat spinal cord.
AB  - In this review, the developmental expression of alpha-, beta- and gamma
      subspecies of protein kinase C (PKC) in the rat spinal cord was summarized, and
      possible roles of this protein for neuronal differentiation were discussed. Faint
      immunoreactivity (IR) for PKCs was first demonstrated in the cervical spinal cord
      on embryonic day 13 (E-13). It gradually became stronger, and between E-18 and
      postnatal day 0 (P-0), strong IR for these three subspecies was uniformly
      distributed throughout the spinal cord. While thereafter, it irregularly
      declined, and reached the adult pattern around P-28 or P-35. The motor neurons
      began to express these three subspecies of PKC in the nucleus, perikaryal
      cytoplasm, dendrites and axons, soon after they began to differentiate. In the
      perikaryal cytoplasm, the IR was expressed mainly on ribosomes, and in the
      dendrites, mainly on cytoskeletal elements. At the late embryonic and early
      postnatal stages, IR for these PKCs was expressed both in the presynaptic
      terminals and on the postsynaptic densities. While thereafter, the IR in the
      former declined, and was detected only on the postsynaptic densities. The dorsal
      corticospinal tract transiently expressed strong IR for these PKCs at the early
      postnatal developmental stages, but thereafter, the IR rapidly declined. The
      developing corticospinal tract fibers expressed strong IR mainly on cytoskeletal
      elements. In contrast, in the mature fibers, IR for alpha-PKC was detected on
      some cytoskeletal elements, and for beta-PKC on almost all cytoskeletal elements,
      but IR for gamma-PKC, mainly on smooth surfaced endoplasmic reticulum. These
      findings suggest that PKC might be involved in several aspects of neuronal
      differentiation such as gene expression, protein synthesis, morphological
      maturation and synapse formation.

PMID- 9550190
TI  - The problem of assessing effective neuroprotection in experimental cerebral
      ischemia.
AB  - In animal models of global and focal ischemia neuroprotection is typically
      determined by quantifying the degree of cell loss or reduction in infarct volume
      shortly after the ischemic insult. These methods are unable to reliably detect
      more subtle forms of neuronal death and dysfunction that arise from injury to non
      homogeneous cell populations (e.g. hilar and striatal neurons), or to dendrites
      (e.g. loss of structural proteins or decreased synaptic transmission). It is
      argued that this type of covert injury contributes to a wide range of functional
      impairments (e.g. decreased working memory, altered field potentials, loss of
      forelimb dexterity) that are rarely used as outcome measures in experimental
      studies even though they are of paramount importance clinically. The limitations
      of a purely histological approach in assessing neuroprotection are clearly
      illustrated using examples of protective drug therapies, mild hypothermia and
      ischemic preconditioning. An alternative strategy that incorporates behavioural,
      electrophysiological and histological endpoints is put forth as a more powerful
      method for gauging neuroprotection. The strength of this approach will be
      increased if these assessments are performed on the same animals. By
      incorporating functional measures and longer postischemic survival into their
      experimental protocols, investigators will increase the validity of their models
      and hopefully reduce the likelihood of advancing ineffective therapies into
      costly clinical trials.

PMID- 9550191
TI  - Ontogeny of the primate fovea: a central issue in retinal development.
AB  - The formation of the primate fovea has fascinated a substantial number of
      histologists, pathologists, ophthalmologists and physiologists for more than a
      century. In this article, using data from the literature as well as our own
      observations, we identify events which we believe are crucial in this process and
      present a developmental neurobiologist's view of the formation of the primate
      fovea. The fovea is a region of the retina specialized for diurnal, high acuity
      functions which require a high spatial density of cone photoreceptors as well as
      a large number of inner retinal cells in order to establish the distinct
      retinofugal pathways (ganglion cell axons) receiving from individual cones in the
      foveal cone mosaic. A unique feature of the fovea is the displacement of cells
      connected to the foveal cones onto the rim of the fovea. It is generally believed
      that this displacement counteracts the problems caused by the scattering of the
      incoming light by cells and blood vessels of the inner retina. We believe that
      one of the crucial events in the formation of the primate fovea is the early
      centripetal migration of photoreceptors towards the central area (centripetal
      displacement). This process, initiated early in development, continues throughout
      intrauterine life until some months or years postnatal. We propose that the
      displacement of cells from the inner layers is related to the earlier
      developmental accumulation of photoreceptors and inner retinal cells centrally.
      This, we propose, leads to metabolic "starvation" of the inner retina, resulting
      from the complete absence of retinal vessels from the vicinity of the incipient
      fovea. It is suggested that these factors in turn trigger centrifugal
      displacement of inner retinal cells towards the encroaching perifoveal capillary
      network and lead to the formation of the foveal depression.

PMID- 9550192
TI  - Glutamate receptors in the mammalian central nervous system.
AB  - Glutamate receptors (GluRs) mediate most of the excitatory neurotransmission in
      the mammalian central nervous system (CNS). In addition, they are involved in
      plastic changes in synaptic transmission as well as excitotoxic neuronal cell
      death that occurs in a variety of acute and chronic neurological disorders. The
      GluRs are divided into two distinct groups, ionotropic and metabotropic
      receptors. The ionotropic receptors (iGluRs) are further subdivided into three
      groups: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and
      N-methyl-D-aspartate (NMDA) receptor channels. The metabotropic receptors
      (mGluRs) are coupled to GTP-binding proteins (G-proteins), and regulate the
      production of intracellular messengers. The application of molecular cloning
      technology has greatly advanced our understanding of the GluR system. To date, at
      least 14 cDNAs of subunit proteins constituting iGluRs and 8 cDNAs of proteins
      constituting mGluRs have been cloned in the mammalian CNS, and the molecular
      structure, distribution and developmental change in the CNS, functional and
      pharmacological properties of each receptor subunit have been elucidated.
      Furthermore, the obtained clones have provided valuable tools for conducting
      studies to clarify the physiological and pathophysiological significances of each
      subunit. For example, the generation of gene knockout mice has disclosed critical
      roles of some GluR subunits in brain functions. In this article, we review recent
      progress in the research for GluRs with special emphasis on the molecular
      diversity of the GluR system and its implications for physiology and pathology of
      the CNS.

PMID- 9550193
TI  - Species-dependence and relationship of morphological and electrophysiological
      properties in nigral compacta neurons.
AB  - The use of animal models in studying disorders of dopaminergic transmission in
      humans, such as Parkinson's disease, depends on the assumption that morphological
      and electrophysiological properties of dopaminergic neurons in the pars compacta
      of the substantia nigra are relatively constant from rodents to monkeys and
      humans. While the electrophysiological properties of nigral dopaminergic neurons
      are highly characteristic and appear to be remarkably uniform, morphological
      studies of nigral compacta neurons have shown significant size differences across
      mammalian species. This discrepancy between morphological and
      electrophysiological characteristics could be reconciled if scaling of neuronal
      size between species was such that intrinsic properties and responses to afferent
      inputs would not be affected. We review the principles of morphological scaling
      of compacta neurons and address this problem by construction and analysis of
      specific passive and active membrane models. These demonstrate that the size
      differences between compacta neurons from rats to primates lead to distinct
      intrinsic electrophysiological properties and that even conservative scaling is
      not sufficient to ensure constant activity patterns unless further compensatory
      mechanisms are present. Comparisons with experimental data show that the
      electrophysiological properties of compacta neurons are characteristic compared
      to other neuronal types but less uniform than generally recognized. The available
      data are not sufficient to prove a specific relationship between morphological
      and electrophysiological properties of compacta neurons but it is evident that
      they provide no support to the assumption that dopaminergic neurons have similar
      properties across mammalian species. Thus, comparative experimental studies are
      required to establish the validity of animal models for nigral function and
      pathology in humans.

PMID- 9550194
TI  - Farewell to the 20th century and reproductive ill-health.

PMID- 9550195
TI  - Preeclamptic nephropathy -- an endothelial lesion. A morphological study with a
      review of the literature.
AB  - OBJECTIVE: We investigated wether an endothelial lesion, postulated in
      pathogenesis of preeclampsia (PE) in general, is also pathogenetically relevant
      in the characteristic renal lesions of PE, presenting as special glomerular
      alterations, designated as "preeclamptic nephropathy". STUDY DESIGN: Renal
      biopsies of 90 women with PE were analyzed by light microscopy (LM),
      immunohistology (IH) and electron microscopy (EM). Corresponding with clinical
      data clinicomorphological correlations were performed. RESULTS: In IH and EM the
      altered glomeruli demonstrate an endothelial lesion. Consecutive morphological
      reactions could be revealed by EM, allowing a subdivision in different stages of
      disease. The late stage indicates the reversibility of these renal lesions. Close
      correlations were found between clinical and morphological data. Focal
      glomerulosclerosis presents a hyperperfusion lesion, developing only
      facultatively in PE as a result of hyperfiltration. CONCLUSION: In preeclamptic
      nephropathy the first morphological substrate of renal changes with the key to
      pathogenesis presents itself as an endothelial lesion. This results in a
      disturbance of glomerular basement membrane permeability and in an imbalance of
      different mediator systems, with dominance of vasoconstrictive reactions but also
      coagulative-, reparation-, and proliferation-processes, leading to the
      characteristic glomerular alterations of preeclamptic nephropathy.

PMID- 9550196
TI  - Transient fetal cerebral dysfunction after road traffic accident. A case report.
AB  - We present a case at 30 weeks gestation with transient abnormal fetal cerebral
      function after a road traffic accident, with loss of fetal movements and abnormal
      FHR tracings for almost 1 week. The pregnancy had after this incident a normal
      course and a healthy baby boy was born at term. We suggest the mechanism to be
      related to fetal hypoxia after excessive maternal psychological stress.

PMID- 9550197
TI  - Effect of angiotensin infusion on plasma endothelin in pregnancy.
AB  - OBJECTIVE: To study a possible role of plasma endothelin in angiotensin-induced
      vasoconstriction. STUDY DESIGN: Plasma endothelin levels were measured before and
      after an angiotensin sensitivity test at 32 gestational weeks in 19 nulliparous
      women. RESULTS: No significant change in plasma endothelin occurred as a result
      of angiotensin infusion. CONCLUSION: The angiotensin-induced rise in diastolic
      blood pressure is not associated with changes in plasma endothelin.

PMID- 9550198
TI  - Reproductive age mortality survey to study under-reporting of maternal mortality
      in Surinam.
AB  - OBJECTIVES: A nationwide confidential enquiry into maternal deaths was carried
      out in Surinam during the years 1991-1993. Preliminary analysis showed a maternal
      mortality ratio (MMR) of 240 per 100000 live births, which was almost four times
      higher than the official MMR for the preceding decade. The question arose whether
      maternal deaths had been under-reported for the years 1981-1990. For these 10
      years official statistics revealed 65 maternal deaths. METHODS: For the period
      1981-1990 a retrospective reproductive age mortality survey was carried out in
      five urban hospitals covering 78% of all deliveries in Surinam. RESULTS: In these
      hospitals 1216 women of age 10-49 years died. Due to disorganized filing 439
      medical records (36%) could not be traced. By reviewing 64% of the records, 85
      maternal deaths were identified (70 direct and 15 indirect). CONCLUSION: Although
      only 64% of medical records could be reviewed, the number of maternal deaths
      identified in five hospitals (85) was 1.3 times higher than the officially
      reported number for the whole country (65). Maternal mortality was found
      therefore to be under-reported in Surinam for the period 1981-1990.

PMID- 9550199
TI  - The addition of indomethacin to betamimetics for tocolysis: any benefit for the
      neonate?
AB  - OBJECTIVE: To study the influence on the neonate of indomethacin administered to
      the mother as an additional tocolytic. STUDY DESIGN: The neonatal outcome in 76
      closely matched low birth weight infants was compared retrospectively: those
      whose mothers received indomethacin together with betamimetics formed the study
      group, those whose mothers received only betamimetics formed the control group.
      RESULTS: There was an increased incidence of respiratory distress syndrome (RDS)
      in the study group (97% versus 45%; P<0.001), an increased need for surfactant
      use (68% versus 26%; P<0.001) and increased ventilatory support, and an increased
      incidence of bronchopulmonary dysplasia (BPD) (47% versus 24%; P=0.03). Gestation
      could not be prolonged significantly by the addition of indomethacin. CONCLUSION:
      Indomethacin as an additional tocolytic agent was associated with an increased
      incidence of RDS, surfactant use and BPD but did not significantly prolong
      gestation.

PMID- 9550200
TI  - Does lunar position influence the time of delivery? A statistical analysis.
AB  - OBJECTIVE: To study the relationship between lunar position and the day of
      delivery; to investigate the synodic distribution of spontaneous deliveries,
      especially in relation to the presence of a full moon. STUDY DESIGN:
      Retrospective analysis of 1248 spontaneous full-term deliveries in three-year
      period (36 lunar months), setted at Department of Obstetrics and Gynaecology,
      Civil Hospital, Fano (Marche, Italy), using circular statistics techniques.
      RESULTS: A connection between the distribution of spontaneous full-term
      deliveries and the lunar month was found. The effect of the phases of the moon
      seems to be particularly relevant in multiparae and plurigravidae; in these
      cases, the mean day of delivery corresponds to the first or second day after the
      full moon. CONCLUSIONS: In this paper the effect of lunar phases on the time of
      delivery is shown. This influence seems to be especially relevant in the case of
      multiparae and plurigravidae. Nevertheless, it is too weak to allow for
      prediction regarding the days with the highest frequency of deliveries.

PMID- 9550201
TI  - Fetal macrosomia: risk factors and outcome. A study of the outcome concerning 100
      cases >4500 g.
AB  - OBJECTIVE: Because difficult vaginal delivery is more frequent with macrosomic
      fetuses, some authors recommend routine caesarean section for the delivery of
      fetuses >4500 g. The purpose of this study was to evaluate the appropriateness of
      this recommendation, in particular, to analyze maternal and fetal complications
      according to the mode of delivery. METHOD: Maternal and neonatal records of 100
      infants with weights of at least 4500 g were identified retrospectively from
      January 1991 to December 1996. Outcome variables included the mode of delivery
      and the incidence of maternal and perinatal complications. RESULTS: The study
      sample consisted of 100 infant and mother pairs. Macrosomic fetuses represented
      0.95% of all deliveries during this period and only ten were >5000 g. Mean birth
      weight was 4730 g (maximum, 5780 g). Gestational diabetes was present in nineteen
      patients. Diabetes was present in three patients. A trial of labour was allowed
      in 87 women, and elective caesarean delivery was performed in thirteen patients.
      The overall cesarean rate, including elective caesarean delivery and failed trial
      of labour, was 36%. Of those undergoing a trial of labour, 73% (64/87) delivered
      vaginally. Shoulder dystocia occurred fourteen times (22% of vaginal deliveries)
      and it was the most frequent complication in our series. There were five cases of
      Erb's palsy, one of which was associated with humeral fracture, and four cases of
      clavicular fracture. By three months of age, all affected infants were without
      sequelae. There was no related perinatal mortality and only two cases of birth
      asphyxia. Maternal complications with vaginal delivery of macrosomic infants
      included a high incidence of lacerations requiring repair (eleven cases). No
      complications were noticed in the patients who had a caesarean section.
      CONCLUSION: Vaginal delivery is a reasonable alternative to elective cesarean
      section for infants with estimated birth weights of less than 5000 g and a trial
      of labour can be offered. For the fetuses with estimated birth weight >5000 g, an
      elective caesarean section should be recommended, especially in primiparous
      women.

PMID- 9550202
TI  - Influence of leukotrienes on in vitro growth of human mammary carcinoma cell line
      MCF-7.
AB  - OBJECTIVES: The aim of this work was to study the action of leukotrienes on the
      growth of human mammary cancer cells MCF-7. STUDY DESIGN: The growth of the cells
      was measured by incorporation of 3H-thymidine. The action of leukotriene (LT)B4,
      LTD4, LTC4, LTE4 or arachidonate (AA) was tested in human mammary cancer cells
      MCF-7 in vitro. RESULTS: LTB4 or LTD4 but not LTC4 or LTE4 reduced significant
      incorporation of 3H-thymidine in MCF-7 cells up to 52% or 56% respectively, when
      administered in concentrations 0.1-1000 pM. Agents in concentrations of 0.01 pM
      or 10000 pM did not effect 3H-thymidine incorporation. We have shown, that MCF-7
      cells synthesise LTB4 when treated with calcium ionophor A23187 (10 microM).
      Leukotriene-antagonist LY171883 (10 microM) lifts inhibitory effects of LTB4 or
      LTD4. Arachidonic acid (10 microM) inhibits 3H-thymidine incorporation up to 72%.
      5-lipoxygenase inhibitor MK-886 (100 nM) lifts the inhibitory effect of
      arachidonate. CONCLUSIONS: LTB4 or LTD4 inhibits MCF-7 breast cancer cell growth.
      LT-receptors mediate the growth-inhibitory effect of LTB4 or LTD4.

PMID- 9550203
TI  - Selection bias in a study on how women experienced induced abortion.
AB  - OBJECTIVE: One third of the women who had an induced abortion at the department
      of gynecology and obstetrics in Malmo 1989 refused to participate in an interview
      a year later to explore their experience and the care they had received. Using
      data from the mandatory preoperative visit it was then possible to compare
      participants with non-participants with regard to socio-demographic
      characteristics. reproductive history and stated reason for abortion. By
      continued follow-up of medical records it has furthermore been possible to
      ascertain how many women conceived within a year, and how many of them applied
      for another abortion and how many elected to continue the pregnancy to term.
      SETTING: Department of Obstetrics and Gynecology, Lund University, University
      Hospital, Malmo Sweden. This is the sole referral hospital serving the population
      of Malmo (approx. 230000). SUBJECTS: All 1285 women who underwent induced
      abortion at the department in 1989. + STUDY DESIGN: In each case information on
      socio-demographic characteristics, reproductive history and stated reasons for
      abortion was collected at the mandatory clinical visit prior to the abortion.
      This information was used for comparison of participants and non-participants in
      the planned 1-year follow-up interview. RESULTS: Young, unmarried women of low
      educational status and without full-time employment or studying were
      overrepresented in the non-participant group. The proportion of women with
      children was however smaller in that group. Within 12 months after the abortion,
      118 women 66 (7.7%) of the participants in the follow-up interview and 52 (12%)
      of the non-participants conceived again but elected to continue the pregnancy to
      term (P<0.05). whereas 124 of the women 80 (9.5%) and 44 (10.2%) of the
      respective subgroups again applied for abortion within 12 months. CONCLUSION: One
      third of the women who underwent induced abortion did not wish to be interviewed
      about their emotional and somatic experience of the abortion 1 year later. Non
      participation at the follow-up interview was associated with socio-demographic
      factors which in studies about other medical problems have been shown to be
      associated with increased vulnerability and morbidity. Non-participation was also
      associated with an increased childbirth rate during the following 2 years. The
      large proportion of non-participants is a matter for concern as to some extent it
      reflects inability of the health care system to establish trustful relationships
      with these women. How the participants in the follow-up study experienced this
      relationship will soon be published in our next paper. Support from the women's
      surroundings and the adviser the women met at the public health care system
      clearly influenced the women's psychological reactions after the abortion. It is
      therefore important to ascertain to what extent the management of abortion
      applicants in fact fulfils their individual needs and expectations.

PMID- 9550204
TI  - Screening for psychologically traumatized rape victims.
AB  - OBJECTIVE: This study aimed to determine whether the General Health
      Questionnaire, a simple psychological screening instrument, could be useful to
      non-specialists in screening for psychologically traumatized rape victims. STUDY
      DESIGN: 285 rape victims (mean age 22.5, men 8%) attending consecutively a
      Consultation for Victims of Psychological Trauma at the University Hospital in
      Tours, France, were assessed through the Structured Interview for Post-Traumatic
      Stress Disorder (SI-PTSD), and the French 28-item version of the self-rated
      General Health Questionnaire (GHQ-28). RESULTS: 70% had Post-Traumatic Stress
      Disorder (PTSD) and 72% a GHQ-28 overthreshold score. The principal component
      analysis of the GHQ-28 ratings yielded a 4-factor solution: social dysfunction,
      feeling of foreshortened future type of depression, somatoform complaints and
      hyperalertness anxiety. GHQ-28 reliability and validity in screening for PTSD
      were studied through computation of Cronbach's alpha coefficient (0.95),
      sensitivity (88%) and positive predictive value (86%). CONCCLUSION: Using the GHQ
      28 is valid and appropriate for practical use.

PMID- 9550205
TI  - Endometrial resectoscopic ablation in patients with menometrorrhagia as a side
      effect of anticoagulant therapy.
AB  - OBJECTIVE: The study was conducted to examine the effect of endometrial ablation
      therapy for patients suffering from coagulation abnormalities and presenting with
      failed medical treatment for menometrorrhagia. STUDY DESIGN: Eleven patients with
      a mean age of 42 years (range 39-45) and with coagulation disorders in whom
      medical therapy for abnormal uterine bleeding was unsuccessful, were treated by
      the ablation procedure under video monitoring. Complications, length of
      hospitalisation and long-term follow-up were noted. The age of the patients
      ranged from 39-45 years. Menstrual characteristics were scored, but blood loss
      before and after the procedure was not quantified. RESULTS: Uterine fibroids were
      found in two patients. The duration of the ablation procedure was 20 min and was
      prolonged for 30 to 40 min when fibroids were diagnosed. During the operation, no
      excessive bleeding was noted in ten patients and postoperative recovery was rapid
      in all. After a one-year follow-up the overall satisfaction of the patients was
      high (10/11). CONCLUSIONS: Our initial experience with a selected group of
      patients suffering from coagulation abnormalities is promising. Bearing in mind
      the risks of a major operation in this group of patients, endometrial ablation
      should be seriously considered.

PMID- 9550206
TI  - Evaluation of ovarian tumors in postmenopausal women by transvaginal sonography.
AB  - OBJECTIVE: The aim of the present study was the evaluation of simple reproducible
      sonomorphological criteria for the preoperative evaluation of ovarian tumors in
      postmenopausal women by use of transvaginal sonography. STUDY DESIGN:
      Postmenopausal women (> or =1 year of secondary amenorrhea) with ovarian tumors
      (n=378; tumors > or =3 cm and <3 cm but with solid parts) were examined in a
      prospective study by transvaginal sonography prior to surgery between 1987 and
      1993. The sonomorphological criteria were correlated with the histological
      findings of the tumors. RESULTS: Of all ovarian tumors in postmenopausal women,
      6.3% were functional cysts (follicular or corpus luteum cysts). Almost all of
      them were detected within the first 5 years of postmenopause. The other ovarian
      tumors were diagnosed as retention cysts (17.5%), benign neoplasms (39.4%), and
      malignant tumors (36.8%). Simple ovarian cysts (monolocular, smooth inner wall)
      represented sonomorphologically the second most frequent type of ovarian tumors
      in postmenopausal women (35.7%). Of these tumors, 9.6% were diagnosed as
      malignant. CONCLUSIONS: Simple reproducible sonomorphological criteria proved to
      be a useful clinical parameter in the preoperative evaluation of ovarian tumors.

PMID- 9550207
TI  - Pelvic floor exercises versus vaginal weight cones in genuine stress
      incontinence.
AB  - OBJECTIVE: To compare pelvic floor exercises and vaginal weight cones in the
      treatment of genuine stress incontinence. STUDY DESIGN: Randomised controlled
      trial. METHODS: Sixty ambulatory and fit white women (mean age 56 years) with
      urinary stress incontinence, treated by a single physiotherapist as outpatients
      during twelve weeks. Thirty women were allocated to a weekly session of pelvic
      floor exercises. Thirty were allocated to using cones, they were seen every two
      weeks. OUTCOME MEASURES: Objective: stress test, vaginal squeezing capacity.
      Subjective: urinary diary, visual analogue scales. RESULTS: Characteristics of
      both study groups were comparable. Unfortunately, there was an early withdrawal
      of fourteen (47%) women in the group treated with cones, and none in the other
      group. Therefore the pelvic floor exercise group was compared not only with the
      group intended to be treated with cones, but also with the selected group that
      only received cone therapy. No statistically significantly differences in outcome
      measures were found between the groups: 53% in the group assigned to pelvic floor
      exercises and 57% into the group assigned to cones, of which 50% in the group
      actually treated with cones, considered themselves as cured or improved to a
      significant degree. Long-term follow-up was not possible as all cone users
      refused continued exercises with cones once the twelve weeks had ended.
      CONCLUSION: Pelvic floor exercises and cones are equally effective in the
      treatment of genuine stress incontinence. Cones are cost and time saving.
      However, the low patient compliance with the cones importantly limits its
      clinical applicability, especially in the long run. Therefore, we do not
      recommend the use of cones.

PMID- 9550209
TI  - Endometriosis and spontaneous abortion rate: a cohort study in infertile women.
AB  - OBJECTIVE: To ascertain if there is an association between endometriosis and
      spontaneous abortion. DESIGN: Prospective cohort study. SETTING: Medical School
      Hospital. POPULATION: 174 infertile women laparoscopically diagnosed with
      endometriosis and 174 infertile women in which endometriosis was ruled out by
      laparoscopy, in the same period of time. MAIN OUTCOME MEASURE: Spontaneous
      abortion. Non-progressive gestational sac and/or histological study. RESULTS: Per
      woman abortion rate was 7.47% (13/174) in the endometriosis group, similar to
      5.74% (10/174) in the infertile women without endometriosis (RR=1.32: CI=0.53
      3.36). Nor were there any differences in the per pregnancy abortion rate: 20.96%
      (13/62) in endometriosis vs. 16.94% (10/59) in non-endometriosis (RR=1.3; CI=0.47
      3.57). The abortion rate was similar in the different AFS stages: 22.86% (8/35)
      in stage I, 16.67% (3/18) in II, 25% (1/4) in III and 20% (1/5) in IV. In stage I
      no differences were observed in patients who were managed expectantly or with
      medical treatment. CONCLUSION: Endometriosis is not associated with an increased
      abortion rate. The severity of disease expressed by AFS staging is not associated
      with an increase in the abortion rate. In stage I the treatment of endometriosis
      did not decrease abortion rates.

PMID- 9550208
TI  - Treatment of carcinoma of the uterine cervix with concomitant cisplatin, 5
      fluorouracil and split course hyperfractionated radiotherapy.
AB  - To improve local and systemic control of bulky (>4 cm) and/or advanced primary
      cancer of the uterine cervix, 35 patients were treated with concomitant cisplatin
      (CDDP), 5-fluorouracil (5-FU) and split course hyperfractionated radiotherapy.
      Radiation was administered to the pelvis in five-day courses at a dose of 1.5 Gy
      twice daily every 21 days until a median dose of 45 Gy was reached. 15 Gy more
      were administered to involved parametrium or central tumor by external
      radiotherapy or brachytherapy. The irradiated zone was extended to include
      paraaortic lymph nodes if necessary. CDDP was administered at a dose of 20 mg m(
      2) and 5 FU at a dose of 500 mg m(-2) from day one to day five of each course.
      The median number of combined treatment courses per patient was four (1-6). Local
      responses were obtained in 19 out of 24 patients in whom evaluation was feasible
      (i.e. who did not undergo surgery prior to combined therapy). Median survival was
      not attained with a median follow up of 33 months, three year overall survival
      was 62% and 52% in patients with local control and in the whole population
      respectively. Several patients with stage III and IV tumors achieved a very long
      survival. Acute toxicity was manageable but three patients required surgical
      repair of late radiation complications. This combined chemotherapy and
      radiotherapy resulted in good local control and did not rule out surgery.

PMID- 9550211
TI  - Unusually prolonged ovarian function ending in endometrial cancer development. A
      case report.
AB  - An unusual case of overprolonged ovarian function in a 77-year-old woman that
      ended in the development of endometrial cancer is presented in this paper. The
      established knowledge of the correlation of uncontrolled oestrogen activity to
      this type of cancer is evaluated and correlated with our patient's hormonal
      readings.

PMID- 9550210
TI  - Fetal Candida sepsis at midgestation: a case report.
AB  - A patient presented with intrauterine fetal death at 21 weeks. A Candida
      vaginitis was treated at 18 weeks of gestation. Fatal fetal Candida sepsis caused
      by Candida albicans can occur in the absence of known risk factors such as
      prolonged rupture of membranes, the presence of an intrauterine contraceptive
      device or cervical cerclage.

PMID- 9550213
TI  - Plasmodium falciparum: in vitro chloroquine susceptibility and allele-specific
      PCR detection of Pfmdr1 Asn86Tyr polymorphism in Lambarene, Gabon.
AB  - Plasmodium falciparum resistance to chloroquine has been described in many parts
      of the world particularly in Africa where malaria is endemic. High levels of
      chloroquine resistance in our study area, Lambarene-Gabon, has led to the use of
      an alternative regimen for treatment and prevention of P. falciparum infection.
      In this study, we examined the in vitro chloroquine sensitivity of 15 isolates
      from this area and assessed the prevalence of a putative chloroquine resistance
      associated Pfmdr1 polymorphism (Asn86Tyr) using a novel allele-specific
      polymerase chain reaction (PCR). Only 4 of the isolates examined were chloroquine
      sensitive. The allele-specific PCR shows that all 15 isolates carried the variant
      (86Tyr) codon. Eleven of these were resistant to chloroquine suggesting a 73%
      agreement between chloroquine resistance phenotype and the point mutation. This
      molecular marker was examined in a further 73 Gabonese isolates, where 58 (79.5%)
      showed 86Tyr and 15 (20.5%) showed 86Asn. In all, 4 (4.5%) of the 88 isolates
      assessed carry both mutant and wild-type codons, suggesting mixed parasite
      populations. The incomplete agreement found between chloroquine resistance
      phenotype and Pfmdr1 (86Tyr) polymorphism would support the view that other
      genetic factors as well as Pfmdr1 may be involved in chloroquine resistance.
      While our results suggest a high prevalence of 86Tyr polymorphism in Lambarene,
      the Asp1246Tyr polymorphism (a point mutation which to date has only been
      associated with South American P. falciparum) seems to be absent in our study
      area.

PMID- 9550212
TI  - Development and comparison of quantitative assays for the dihydropteroate
      synthetase codon 540 mutation associated with sulfadoxine resistance in
      Plasmodium falciparum.
AB  - A point mutation in codon 540 of the dihydropteroate synthetase (dhps) gene
      affecting sulfadoxine resistance has previously been found in parasites from
      patients with Plasmodium falciparum infection. Here, we investigated 4 methods of
      identifying this mutation in clinical specimens and established a reliable
      quantitative assay to estimate the percentage of resistant type in mixed
      infections. A diagnostic PCR assay based on allele-specific amplification was
      developed, which clearly typed the clinical specimens examined. The mutation in
      codon 540 introduces an additional FokI cleavage site which provided a second
      method to differentiate mutant from wild type, where the former gives rise to 2
      characteristic fragments of 538 and 326 bp that are absent from the latter. To
      calibrate quantitatively the ratio of alleles in mixed samples, we constructed
      artificial mixes containing 2 plasmid DNAs, one carrying the mutation and the
      other a wild-type insert. When 32P-labelling was employed, the allele-specific
      PCR assay could detect the level of resistant type in a mixture down to 0.1-1%,
      while for the restriction enzyme/PCR analysis, the figure was approximately 10%.
      Furthermore, neither fluorescent dye-labelled terminator nor dye-labelled primer
      cycle sequencing was able to detect the mutant allele if it was present at less
      than 20-30%. We conclude that the allele-specific PCR assay is the most sensitive
      method of detecting the codon 540 mutation in P. falciparum dhps, and the method
      of choice for estimating the composition of mixed samples.

PMID- 9550214
TI  - Vaccination of langur monkeys (Presbytis entellus) against Leishmania donovani
      with autoclaved L. major plus BCG.
AB  - The protective potential of killed Leishmania major (ALM) along with BCG was
      evaluated against L. donovani in Indian langur monkeys in single and triple dose
      schedules. A delayed protection was observed in monkeys after a single dose
      schedule of ALM (3 mg)+BCG (3 mg) given intradermally 2 months before intravenous
      challenge with L. donovani. Triple dose schedule each of 1 mg ALM + 1 mg BCG was
      more effective. The status remained unchanged until the end of the experiment
      (approximately 8 months). The study indicates that a combination of ALM + BCG may
      be a good candidate vaccine for exploiting against human Kala-azar.

PMID- 9550216
TI  - The effect of praziquantel treatment on glutathione concentration in Schistosoma
      mansoni.
AB  - A fluorescent dye monochlorobimane (MCB) that binds glutathione (GSH) was used as
      a tool for measuring the concentration of GSH in skin and mechanically
      transformed schistosomula. The specificity of MCB binding to GSH was confirmed by
      thin layer chromatography (TLC) and high performance liquid chromatography
      (HPLC). The MCB binding to GSH is an energy-dependent process since no labelling
      could be seen at low temperature. When 24-h-old schistosomula were depleted of
      GSH by buthionine sulfoximine (a specific inhibitor of GSH synthesis) for 18 h, a
      significant decrease (P < 0.001) in fluorescence was observed. PZQ treatment of
      the schistosomula after first labelling the parasites with MCB did not greatly
      affect MCB binding to GSH. However, when the 24-h-old schistosomula were first
      PZQ treated and afterwards labelled with MCB, the pattern of labelling was
      identical to that of those of the non-labelled parasites. When 24-h-old
      schistosomula were first PZQ treated, washed and labelled in the presence of 1 mM
      GSH, the level of fluorescence was recovered. These results suggest that PZQ
      depletes GSH from schistosomula, and may render them susceptible to the host's
      immune system.

PMID- 9550215
TI  - Metastasis of Theileria annulata macroschizont-infected cells in scid mice is
      mediated by matrix metalloproteinases.
AB  - Theileria annulata (Ta)-infected leucocytes are able to disseminate in scid mice.
      The dose of virulent parasites of the Ta-Ode line required to achieve
      quantifiable dissemination was found to be 2 x 10(6) cells given i.p.
      Dissemination was higher on day 11 post-inoculation than on day 18. The
      attenuated Ta-Ode cells were found to disseminate very poorly compared to their
      virulent progenitors, which correlates with a marked reduction in matrix
      metalloproteinase (MMP) expression. A daily i.p. injection of mice with BB94, a
      synthetic inhibitor of MMPs, almost completely ablated dissemination compared to
      controls. This provides strong evidence that metastasis of Theileria annulata
      macroschizont-infected host cells is mediated by host MMPs induced by the
      parasite. This has important implications for explaining a number of pathological
      features of tropical theileriosis in cattle.

PMID- 9550217
TI  - Schistosome-induced portacaval haemodynamic changes in Rattus rattus are
      associated with translocation of adult worms to the lungs.
AB  - The presence of naturally portacaval shunts has been investigated in the
      vasculature of normal and Schistosoma mansoni-infected Rattus rattus. Using the
      technique of injecting Polystyrene microspheres in the superior mesenteric vein,
      we demonstrated that the presence of adult schistosomes in the lungs of R. rattus
      was not due to an innate anomaly of the rat vasculature but resulted from the
      formation of portacaval shunts during infection. In rats harbouring a bisexual
      infection, microspheres were only detected in the lungs from week 7. The
      development and increasing size of the shunts were maximal between weeks 7 and 10
      and coincident with the translocation of adult worms from the portal tract to the
      lungs. At weeks 20-25, only 1-2% of the microspheres were recovered from the
      lungs, suggesting that the portacaval anastomoses have regressed due to reduction
      in portal hypertension after worm translocation. R. rattus with a male-only
      schistosome infection harboured adult worms in the lungs, indicating that the
      development of shunts does not solely depend upon egg deposition in the liver to
      generate hypertension. The relationships between the presence of the schistosomes
      in the lungs, the portacaval shunting and the resistance to reinfection is
      discussed.

PMID- 9550219
TI  - Mast cell distribution in nodules of Onchocerca volvulus from untreated patients
      with generalized onchocerciasis.
AB  - Onchocercomata with a defined worm population were analysed to elucidate the
      distribution of mast cells. Nodules with live females were classified according
      to the presence or absence of microfilariae. Immunohistochemical staining was
      performed using antibodies specific for mast cells or IgE. Mast cells appeared
      singly or in diffuse accumulations perivascularly and in inflammatory infiltrates
      between adult Onchocerca volvulus and in the capsular area. No mast cells were
      detected in cystic parts. Only few, scattered mast cells were found in the
      fibrous zone around the adult worm. They were increased with stronger
      infiltration and hence, related to the inflammatory cells. Mast cells were never
      localized directly at adult worms or microfilariae. A correlation of the mast
      cell distribution to the occurrence of eosinophils was observed regarding higher
      numbers of mast cells and eosinophils in nodules with microfilariae-producing
      females. Nodules with single males revealed higher numbers of mast cells than
      nodules with non-producing females, although both contained very few eosinophils.
      Onchocercomata with dead worms contained significantly more mast cells than those
      with live filariae. In conclusion, the localization and frequency of mast cells
      is contingent on the vitality and productivity of the worms and therefore,
      indirectly and directly on the release of O. volvulus antigens.

PMID- 9550218
TI  - The relationship between microfilarial load in the human host and uptake and
      development of Wuchereria bancrofti microfilariae by Culex quinquefasciatus: a
      study under natural conditions.
AB  - The uptake of Wuchereria bancrofti microfilariae (Mf) by Culex quinquefasciatus
      and their development in relation to human Mf density were quantified by allowing
      a total of 1096 wild mosquitoes to feed on 13 volunteers sleeping under partially
      open bed-nets. For each volunteer, each hour between 18.00 and 06.00 h the Mf
      density in finger-prick blood was determined and engorged mosquitoes collected.
      Each hourly collection of mosquitoes was kept separately. Half of them was
      dissected within 18 h post-feeding for the presence of ingested Mf, the other
      half was reared for 12 days to allow for the development of L3 larvae. About 20%
      of the latter mosquitoes died during these 12 days and these harboured
      significantly more larvae than the surviving ones, which could be an indication
      of excess-mortality among heavily infected mosquitoes. Assuming that variability
      in Mf uptake and in the number of developed L3 larvae can be described by a
      negative binomial distribution, a maximum-likelihood procedure was applied to
      estimate the relationship between human Mf density and both the arithmetic mean
      Mf uptake and L3 development. Both were adequately described by a saturating
      hyperbolic function that significantly differed from linearity. The saturation
      level for Mf was estimated at 29 (CI: 20-54) and for L3 larvae at 6.6 (CI: 4.3
      17.0). Next, the L3 yield was related to Mf uptake indicating that the W.
      bancrofti-C. quinquefasciatus complex shows 'limitation', i.e. a decreasing yield
      for an increasing uptake. Both the number of Mf ingested and the number of L3
      larvae developing per mosquito were found to be highly aggregated, with the level
      of aggregation decreasing in a non-linear way with human Mf density.

PMID- 9550220
TI  - Social structure of the mara (Dolichotis patagonum) as a determinant of gastro
      intestinal parasitism.
AB  - A one-year study of gastro-intestinal parasitism in a free-ranging population of
      maras at Whipsnade Wild Animal Park, UK, revealed a strong relationship between
      membership of social units and both intensity and prevalence of infection. The
      mara, a hystricomorph rodent from southern Argentina, has a social organization
      including both monogamy and communal denning of the young, an apparently unique
      combination among mammals. From October 1992 to September 1993, strongyloid
      parasite loads were estimated from faecal egg counts. A minimum adequate model
      was fitted to the data using the Genstat statistical package. This showed that
      family membership had a highly significant effect on the intensity of egg
      shedding in faeces, and a significant effect on the prevalence of infection.
      After controlling for both extrinsic environmental and intrinsic demographic
      factors, homogeneity of infection was greater within than between families and
      adult pairs.

PMID- 9550221
TI  - Modulation of the motility of the vagina vera of Ascaris suum in vitro by FMRF
      amide-related peptides.
AB  - Ascaris suum contains a large number of FMRFamide-related peptides (FaRPs) of
      which KNEFIRFamide (AF1), KHEYLRFamide (AF2) and KSAYMRFamide (AF8, also called
      PF3) have been extensively studied and are known to exert actions on somatic
      muscle strips of the worm. In the present study, the effects of AF1, AF2 and AF8
      on the activity of the vagina vera of female A. suum have been examined in vitro.
      The vagina vera is a muscular tube connecting the uterus and vagina uteri to the
      gonopore and is probably involved in regulating egg output. The tissue exhibited
      spontaneous, rhythmic contractions in vitro, which were modulated by each of the
      FaRPs tested. The effects of each of the peptides were qualitatively and
      quantitatively different, and in each case were reversible. AF1 (1 microM) caused
      a biphasic response in the form of a transient lengthening of the preparation,
      followed by a shortening; contractions were initially inhibited but resumed 5 min
      post-addition of the peptide. Lower concentrations (< or = 0.1 microM) induced a
      less marked effect, with rhythmic contractions returning 5 min post-addition. AF2
      and AF8 reduced contraction frequency at concentrations > or = 0.1 microM. Both
      peptides also caused the tissue to shorten, although the effects of AF8 on
      baseline tension were inconsistent. The apparent potencies of AF1 and AF8 on
      contraction frequency of the vagina vera were 10-fold greater than AF2 and,
      unlike their actions on A. suum somatic body wall muscles, the actions of AF1 and
      AF2 were qualitatively different. Indeed, the effects of each of these FaRPs on
      the vagina vera were markedly different from those observed on the somatic
      muscle.

PMID- 9550222
TI  - Relative merits of nuclear ribosomal internal transcribed spacers and
      mitochondrial CO1 and ND1 genes for distinguishing among Echinostoma species
      (Trematoda).
AB  - Cryptic species, belonging to the 37 collar-spine Echinostoma group, were
      distinguished using nuclear rDNA ITS (884 bases) and mtDNA CO1 (257 bases) and
      ND1 (530 bases) sequences. Sequences were obtained from five 37 collar-spine
      species, Echinostoma trivolvis, E. paraensei, E. caproni, E. revolutum and E.
      sp.I, a parthenogenetic isolate from Africa. Three geographic isolates of E.
      caproni were compared. Average sequence divergence among the 37 collar-spine
      species range from 2.2% in the rDNA ITS through 8% for the CO1 and 14% for the
      ND1. In addition, genes were sequenced from 2 non 37 collar-spine species, E.
      hortense and an undescribed Australian species, E. sp. (Aus). For each gene,
      distances of terminals from a predicted ancestral sequence were calculated. These
      indicated that ND1 is diverging significantly faster than the other 2 regions. In
      the CO1 gene most substitutions are synonymous and saturation has been reached
      for the majority of pairwise comparisons. The ND1 gene exhibits greater pairwise
      divergence but less evidence of saturation due to weaker conservation of first
      and second codon positions. The ITS has no amino acid coding constraints and
      displays no evidence of saturation. Although all 3 regions successfully
      distinguished the nominal species, ND1 appears to be the most informative region
      for investigating relationships within the 37 collar-spine group.

PMID- 9550223
TI  - Tension/stiffness ratio of skinned rat skeletal muscle fibre types at various
      temperatures.
AB  - It is well known that shortening velocity and maximal tension of muscle
      preparations are strongly dependent on experimental temperature. Conversely,
      studies about temperature effects on muscle fibre stiffness are scarce. In the
      present study, we measured tension and stiffness of maximally Ca2+-activated
      skinned rat skeletal muscle fibres of different types over a wide temperature
      range. All fibre types exhibited a similar tension/stiffness ratio at each
      experimental temperature. This ratio increased almost linearly from 6 to 18 nm
      when the temperature was raised from 6 to 34 degrees C. Our results are discussed
      in the light of the drastic discrepancies reported for the amount of compliance
      inside and outside the attached myosin cross-bridges of activated muscle fibres
      (Ford et al. 1981, Huxley et al. 1994, Kojima et al. 1994, Wakabayashi et al.
      1994, Higuchi et al. 1995). The relation between these compliances had been
      deduced from various experimental approaches executed at different temperatures.
      The large temperature sensitivity of the tension/stiffness ratio found in this
      study provides evidence for the assumption that the compliance outside the cross
      bridges increases with rising temperature. This view would reconcile the
      contrasting results reported for the relation of compliances inside and outside
      the attached cross-bridges.

PMID- 9550224
TI  - Hindlimb suspension induces the expression of multiple myosin heavy chain
      isoforms in single fibres of the rat soleus muscle.
AB  - To examine the expression patterns of myosin heavy chain (MHC) isoforms in single
      fibres of the soleus muscle following weightlessness, 10-week-old male Wistar
      rats were subjected to hindlimb suspension for 4 weeks. Hindlimb suspension
      resulted in reduced body weight and absolute and relative mass of the soleus
      muscle compared with controls (P < 0.01). A total of 975, 892 and 1098 single
      fibres from pre-suspended controls, age-matched controls and suspension groups,
      respectively, were subjected to MHC analyses using SDS-PAGE. Single fibres
      containing only MHC I decreased (87.9 vs. 67.9%, P < 0.05) and single fibres
      containing only MHC IIa disappeared after hindlimb suspension. On the contrary,
      single fibres containing multiple type II MHC isoforms were observed as follows:
      10.1% single fibres contained MHCs IIa and IId; 14.1% contained MHCs I, IIa and
      IId; and some (1.4%) expressed the MHC IIb isoform with MHCs IIa and IId. The
      relative content (%) of each MHC isoform in MHC hybrid single fibres was
      calculated using densitometer scanning. The MHCs IIa and IId hybrid single fibres
      contained the same amount of MHC IIa (51.3 +/- 6.3%) and MHC IId (48.7 +/- 6.3%).
      In the MHCs I, IIa and IId hybrid single fibres, the percentage of MHC IIa was
      distributed in a wide range (approximately 80%), whereas the percentage of MHC
      IId was a relatively low range (approximately 40%), and the relative content of
      MHC I was inversely correlated with that of MHC IIa and MHC IId, respectively.
      The fibre type composition of suspended soleus muscle, analysed by histochemical
      myosin ATPase staining, was changed, with a decrease in the percentage of type I
      fibres and an increase in that of type IIA fibres. Our results indicate that
      hindlimb suspension induces multiple type II MHC expression in the soleus single
      fibres and suggest that the single fibres containing multiple type II MHC
      isoforms should be classified into type IIA.

PMID- 9550225
TI  - Effects of bedrest on deltoideus muscle morphology and enzymes.
AB  - To examine the effects of unweighting on the structural and metabolic adaptations
      of a non-postural muscle, deltoideus muscle biopsies were taken in seven male
      healthy subjects, before and after a 37 day bedrest. Myofibrillar ATPase
      histochemistry demonstrated no change in fibre type distributions (I, IIA, IIB),
      in fibre cross-sectional areas nor in capillary supply. No difference was noted
      in enzyme activities of oxidative metabolism (citrate synthase, 3-hydroxy-acyl
      CoA dehydrogenase), and glycolysis (hexokinase, lactate dehydrogenase). Electron
      microscopy showed a decrease in the volume density of lipids but no change in
      mitochondrial volume density and distribution. The results indicate that bedrest
      induces no major morphological and biochemical changes in deltoideus muscle,
      contrary to what was previously reported in vastus lateralis muscle. This lack of
      changes is probably related to an unaltered deltoideus muscle use.

PMID- 9550226
TI  - Effects of selenium deficiency on diaphragmatic function after resistive loading.
AB  - Diaphragmatic fatigue has been associated with increased production of reactive
      oxygen species. Among the defenses against reactive oxygen species is the
      glutathione redox system. The selenium-dependent enzyme glutathione peroxidase is
      an important component of this system. Thus, we hypothesized that selenium
      deficiency would lower glutathione peroxidase activity and render the diaphragm
      more susceptible to a mild exertional protocol. Sprague-Dawley rats were fed a
      selenium-deficient or control diet for 12 weeks then divided into four
      experimental groups: (1) unloaded, basic diet with selenium supplementation
      (control); (2) unloaded, selenium-deficient diet; (3) loaded, basic diet with
      selenium supplementation; and (4) loaded, selenium-deficient diet. Diaphragmatic
      in vitro contractile properties, glutathione peroxidase activity and glutathione
      content were measured. During inspiratory resistive loading, the animals breathed
      against an inspiratory resistor at 70% of maximal airway pressure until the
      target pressure was not achieved for five consecutive breaths. Selenium
      deficiency resulted in a significant decrease in diaphragmatic glutathione
      peroxidase activity, without changes in total glutathione content. Neither
      selenium deficiency nor inspiratory resistive loading alone impaired
      diaphragmatic contractility. Selenium deficiency in conjunction with inspiratory
      resistive loading resulted in a significant decrease in diaphragmatic twitch and
      tetanic force, with a downward shift in the force/frequency curve. These data
      suggest that selenium deficiency lowers diaphragmatic glutathione peroxidase
      activity, and when these animals are subjected to the oxidative stress of
      resistive loading, there is an impairment in muscle function. We conclude that a
      functional glutathione peroxidase is necessary to protect the diaphragm against
      the effects of resistive loading.

PMID- 9550227
TI  - Increase in nitric oxide formation after chronic voluntary exercise in
      spontaneously hypertensive rats.
AB  - The effect of chronic voluntary exercise on the plasma level of nitrate, a major
      stable metabolite of nitric oxide (NO) was studied in spontaneously hypertensive
      rats (SHR). Exercise consisted of spontaneous running in wheels for 3-35 days.
      Blood samples were collected after 3, 7, 14, 21 and 35 days of exercise and all
      samples were drawn after the running wheel had been locked during the preceding
      12 h. The plasma nitrate level was significantly (P < 0.05) elevated in SHR after
      35 days of exercise. Surprisingly after 7 days of exercise a significant (P <
      0.001) decrease in the nitrate level in plasma was noted. Further research is
      needed to elucidate this biphasic change in nitrate seen in this study. The
      elevated level of plasma nitrate seen after 35 days of voluntary exercise was
      still present up to 36 h after termination of exercise. We conclude that exercise
      training in SHR elicits an enhanced formation of NO.

PMID- 9550228
TI  - Receptor potential characteristics during direct stereocilia stimulation of
      isolated outer hair cells from the guinea-pig.
AB  - The receptor potential as a function of stimulus amplitude and frequency was
      studied with the patch-clamp technique in isolated outer hair cells (OHCs) with a
      length ranging from 30 to 87 microm during direct mechanical stimulation of the
      stereocilia. The amplitude and frequency of the stimulation were varied from 125
      nm to 2 microm and from 100 Hz to 2.5 kHz, respectively. The mean resting
      membrane potential before stimulation was -64.25 +/- 1.4 mV (mean +/- SE, n =
      26). Irrespective of the frequency used, stereocilia stimulation produced a
      combination of AC and DC responses, and both components showed saturation with
      increasing stimulation. Frequency responses appeared to be a function of
      intensity and resembled a low-pass filter with a time constant ranging from 0.2
      to 2.0 ms. With increasing stereocilia stimulation, the relative contribution of
      high frequencies to the AC component decreased, suggesting a decrease of the
      corner frequency. The saturated amplitude of the AC component for low-frequency
      stimulation (100 Hz) was proportional to cell length and increased with a mean
      rate of 0.014 mV microm(-1). A relationship between the DC response of the
      receptor potential and the pre-stimulus membrane potential was found. Recordings
      with more negative membrane potentials had greater DC components, while more
      depolarized recordings demonstrated smaller DC components. These fluctuations
      seemed to be defined by the interaction between the probe and stereocilia bundle
      and could be in the range of the transfer function for each cell.

PMID- 9550229
TI  - Nervous control of alkaline secretion in the duodenum as studied by the use of
      cholera toxin in the anaesthetized rat.
AB  - There is experimental evidence for an axon reflex control of alkaline secretion
      in the rat duodenum. We have investigated if there is also an intramural reflex
      control of alkaline secretion similar to that demonstrated with regard to the
      control of the fluid transport in the rat jejunum. Alkaline secretion in the
      duodenum of an anesthetized rat was continuously monitored using an in situ
      titration technique. The segment was extrinsically denervated. Exposing the
      duodenal segment to 80 microg cholera toxin markedly increased alkaline
      secretion. This response was abolished by hexamethonium (28 micromol (10 mg) kg(
      1) body wt), a nicotinic receptor blocker, lidocaine (0.5 mL of a 1% solution on
      the serosal surface), a local anaesthetic, and nifedipine (5.75 micromol (2 mg)
      kg(-1) body wt i.v.), a calcium channel blocker. The response to cholera toxin
      was partially abolished by granisetron (0.11 micromol (40 microg) kg(-1) body wt
      i.v.), a 5-HT3 receptor blocker. Atropine (1.7 micromol (0.5 mg) kg(-1) body wt
      i.v.), a muscarinic receptor blocker, had no effect. We therefore conclude that
      the alkaline secretion in the rat jejunum evoked by cholera toxin exhibits the
      same pharmacological properties as the fluid secretion caused by the toxin in the
      jejunum. This suggests that the alkaline secretion in the rat duodenum is
      controlled not only by an axon reflex but also by an intramural secretory reflex
      similar to that controlling fluid transport in the rat jejunum.

PMID- 9550230
TI  - Is for-profit managed care an oxymoron?

PMID- 9550231
TI  - A physician-owned and -operated behavioral managed care company.

PMID- 9550232
TI  - Estimation of costs of public psychiatric treatment.

PMID- 9550233
TI  - Referrals to psychiatrists.

PMID- 9550234
TI  - Managed care's responsibility for decisions to deny benefits: the ERISA obstacle.
      Employee Retirement Income Security Act.

PMID- 9550235
TI  - The computer as clinician assistant: assessment made simple.

PMID- 9550236
TI  - A college reunion in the psychiatric emergency room.

PMID- 9550237
TI  - Outpatient utilization patterns of integrated and split psychotherapy and
      pharmacotherapy for depression.
AB  - OBJECTIVE: This exploratory study examined utilization and costs among depressed
      patients in two treatment models-integrated treatment, in which psychotherapy and
      pharmacotherapy were provided by a psychiatrist, and split treatment, in which
      pharmacotherapy was provided by a psychiatrist and psychotherapy by a
      nonphysician psychotherapist. METHODS: A quasi-experimental retrospective design
      was used to compare claims data from a national managed mental health care
      organization for 191 patients in integrated treatment and 1,326 in split
      treatment. RESULTS: During the 18-month study, patients receiving integrated
      treatment used significantly fewer outpatient sessions and had significantly
      lower treatment costs, on average, than those in split treatment. Integrated
      treatment appeared to be associated with a pattern of utilization characterized
      by frequent treatment episodes in contrast to that of split treatment, which was
      characterized by more sessions with fewer breaks of 90 days or more. CONCLUSIONS:
      The results do not support the prevailing assumption that integrated treatment is
      more costly than split treatment in a managed care network. Despite limitations
      in the study methods, the strength of these preliminary findings poses a powerful
      challenge and invites further study.

PMID- 9550238
TI  - Persons with severe mental illness in jails and prisons: a review.
AB  - OBJECTIVE: The presence of severely mentally ill persons in jails and prisons is
      an urgent problem. This review examines this problem and makes recommendations
      for preventing and alleviating it. METHODS: MEDLINE, Psychological Abstracts, and
      the Index to Legal Periodicals and Books were searched from 1970, and all
      pertinent references were obtained. RESULTS AND CONCLUSIONS: Clinical studies
      suggest that 6 to 15 percent of persons in city and county jails and 10 to 15
      percent of persons in state prisons have severe mental illness. Offenders with
      severe mental illness generally have acute and chronic mental illness and poor
      functioning. A large proportion are homeless. It appears that a greater
      proportion of mentally ill persons are arrested compared with the general
      population. Factors cited as causes of mentally ill persons' being placed in the
      criminal justice system are deinstitutionalization, more rigid criteria for civil
      commitment, lack of adequate community support for persons with mental illness,
      mentally ill offenders' difficulty gaining access to community treatment, and the
      attitudes of police officers and society. Recommendations include mental health
      consultation to police in the field; formal training of police officers; careful
      screening of incoming jail detainees; diversion to the mental health system of
      mentally ill persons who have committed minor offenses; assertive case management
      and various social control interventions, such as outpatient commitment, court
      ordered treatment, psychiatric conservatorship, and 24-hour structured care;
      involvement of and support for families; and provision of appropriate mental
      health treatment.

PMID- 9550239
TI  - A strategic approach to the psychiatric workforce dilemma.
AB  - To help build consensus in the field of psychiatry about future psychiatric
      manpower needs, a 13-step strategic approach to the workforce issue is described.
      The steps include recognizing the importance of the assumptions that underlie
      workforce requirements; selecting credible and professional leadership with
      vision and courage; adopting a strategic plan to clarify workforce assumptions;
      re-examining the structure and function of established programs; preparing
      trainees for work in the 21st century; preserving psychiatry's humanistic
      tradition; enlisting the support of nonacademic psychiatrists; and reinforcing
      involvement in the fiscal and political aspects of medicine. They also include
      focusing attention on important policy issues; securing the support of patients,
      families, and advocates; endorsing a multidisciplinary, biopsychosocial approach
      to the evaluation and treatment of mental illness; minimizing divisive conflicts
      within and between national organizations; and developing strategic alliances
      with other medical disciplines. Implications of the 13-step approach are outlined
      for psychiatric clinicians, educators, and researchers, as well as for the
      organizations that serve them.

PMID- 9550240
TI  - A national survey of "consumer empowerment" at the state level.
AB  - OBJECTIVE: A national survey was conducted to determine the extent of consumer
      empowerment in the public mental health system. METHODS: A questionnaire was sent
      to mental health authorities in all U.S. states and territories asking whether
      consumer empowerment or responsibility was defined in statutes, regulations, or
      policies and whether consumers or family members were employed in central or
      field offices of the authority. A rating scale measured the extent of consumer
      empowerment, and correlations were examined between this rating and other
      variables. RESULTS: The survey achieved a 100 percent response rate. Twenty-two
      states (39 percent) addressed consumer empowerment and 16 (28 percent) consumer
      responsibility in a statute, regulation, or policy. Twenty-seven states (48
      percent) had paid positions for consumers in central offices, and three (5
      percent) had such positions for family members. Half the states had paid
      positions for consumers in field offices, and 12 states (24 percent) had such
      positions for family members. The extent of a state's consumer empowerment had no
      relationship to region of the country or the state's mental health budget. A
      significant positive relationship was found between extent of empowerment and the
      size of the state's population and the quality of its mental health services.
      CONCLUSIONS: State mental health authorities vary widely in their direct
      involvement with consumer empowerment. Results indicate that mental health
      authorities need to make a greater commitment to the achievement of such
      empowerment if it is to become a meaningful part of government involvement with
      mental health services.

PMID- 9550242
TI  - Use of psychotropic medications for persons with mental retardation who live in
      Oklahoma nursing homes.
AB  - OBJECTIVE: The study examined the use of psychotropic medications to treat
      persons with mental retardation living in nursing homes in Oklahoma. METHODS:
      Data were gathered on all 1,056 individuals funded through the Oklahoma mental
      retardation service system in 1995 to live in nursing homes. The Developmental
      Disabilities Quality Assurance Questionnaire was used to assess adaptive
      behavior, living site conditions, health, use of medications, and other
      variables. RESULTS: The most frequently used class of psychotropic medications
      was antipsychotic medication, used by 31.8 percent of subjects. Sixteen percent
      received anxiolytic medication, and 6.1 percent received antidepressant
      medication. Stepwise multiple regression analysis indicated that use of
      antipsychotic medication was marginally predictable (less than 15 percent of the
      variance was explained) with a linear combination of six variables: mental health
      problems; violence toward others; adaptive behavior; screaming, yelling, or
      crying behavior; hyperactivity; and age. CONCLUSIONS: A relatively high
      percentage of subjects received various forms of psychotropic medications,
      especially antipsychotics. The presence of behavior problems or mental health
      problems did not sufficiently explain the high rate of use of antipsychotic
      medication. The risks of this type of medication and its lower rate of use in
      group homes raise the question of the appropriateness of placing persons with
      mental retardation in nursing homes as they are currently conceived.

PMID- 9550241
TI  - Scheduled intermittent hospitalization for psychiatric patients.
AB  - OBJECTIVE: The effect of scheduled intermittent hospitalization on the hospital
      utilization, community adjustment, and self-esteem of persons with serious and
      persistent mental illness was examined in an experimental study. METHODS: Fifty
      seven male veterans, aged 65 or younger, with a primary axis I psychiatric
      diagnosis who were frequent utilizers of inpatient care over the previous two
      years were randomly assigned to two groups. Patients in the experimental group
      were prescheduled for four hospital admissions, each lasting nine to 11 days, per
      year for two years. Patients in the control group had traditional access to
      hospital care. Psychiatric bed days, community adjustment, and self-esteem were
      assessed during and after the intervention. RESULTS: No differences between the
      groups on demographic or clinical variables were detected at study entry. The
      experimental group showed improvement in self-esteem, affect, and complaints of
      physical symptoms at one year. No statistically significant differences between
      groups were found in hospital utilization, financial management, substance abuse,
      or psychological well-being at one year. CONCLUSIONS: Scheduled intermittent
      hospitalization may be an appropriate and promising alternative to traditional
      care for revolving-door patients. This intervention could maintain patients at a
      higher level of wellness than traditional care and reduce the recurrence of the
      crises that precipitate hospitalization.

PMID- 9550243
TI  - Moving psychiatric patients from hospital to community: views of patients,
      providers, and families.
AB  - OBJECTIVE: Differences in the perspectives of severely and persistently ill
      patients, their family members, and clinical care providers on key aspects of
      community-based care were examined to help inform community service planning and
      development. METHODS: A sample of 183 patients being considered for relocation
      from psychiatric facilities in Alberta, Canada, to community-based care, were
      interviewed, as were their primary clinical care providers. Family members of 130
      patients were also interviewed. RESULTS: Among the 130 patient-family pairs, 41
      percent disagreed about the desirability of relocation, with fewer patients
      favoring relocation than families. Forty-nine percent of the pairs disagreed
      about the desired proximity to the family of the relocated patient, with the
      patient desiring closer proximity than the family member in about half of these
      cases. Fifty-three percent of the pairs disagreed about the amount of financial
      and emotional support that the family would provide after relocation. In half of
      these cases, patients believed the family would provide a higher level of support
      than the family indicated it could. Among the patients, 49 percent preferred
      independent living, whereas only 10 percent of family members and 17 percent of
      clinical care providers preferred it. Fifty-five percent of patients expressed a
      clear desire to work, whereas care providers believed that only 12 percent of
      patients were employable. CONCLUSIONS: Persistently mentally ill residents of
      psychiatric facilities express clear preferences about key aspects of community
      based care when they are asked, and these preferences often reflect different
      views from those expressed by either family members or clinical care providers.

PMID- 9550244
TI  - Changes in the process of care for Medicaid patients with schizophrenia in Utah's
      Prepaid Mental Health Plan.
AB  - OBJECTIVE: Changes in the process of psychiatric care received by Medicaid
      beneficiaries with schizophrenia were examined after the introduction of
      capitated payments for enrollees of some community mental health centers (CMHCs)
      under the Utah Prepaid Mental Health Plan. METHODS: Data from the medical records
      of 200 patients receiving care in CMHCs participating in the prepaid plan were
      compared with data from the records of 200 patients in nonparticipating CMHCs,
      which remained in a fee-for-service reimbursement arrangement. Using the Process
      of Care Review Form, trained abstracters gathered data characterizing general
      patient management, social support, medication management, and medical management
      before implementation of the plan in 1990 and for three follow-up years. Using
      regression techniques, differences in the adjusted changes between third-year
      follow-up and baseline were examined by treatment site. RESULTS: By year 3 at the
      CMHCs participating in the plan, psychotherapy visits decreased, the probability
      of a patient's terminating treatment or being lost to follow-up increased, the
      probability of having a case manager increased, the probability of a crisis visit
      decreased (but still exceeded that at the nonplan sites), and the probability of
      treatment for a month or longer with a suboptimal dosage of antipsychotic
      medication increased. Only modest changes in the process of care were observed at
      the nonplan CMHCs. CONCLUSIONS: Change in the process of psychiatric care was
      more evident at the sites participating in the plan, where traditional
      therapeutic encounters were de-emphasized in response to capitation. The array of
      changes raises questions about the vigor of care provided to a highly vulnerable
      group of patients.

PMID- 9550245
TI  - A naturalistic study of clinical use of risperidone.
AB  - Follow-up data on 97 of the 101 patients at a university-based psychiatric
      hospital for whom risperidone had been prescribed between February 1994, when the
      medication was introduced, and October 1996 were reviewed an average of 102 weeks
      after the start of the medication. Only 28.9 percent of the patients were still
      on risperidone at follow-up. Patients who were maintained on risperidone were
      able to tolerate a higher dose with fewer side effects. The most common reasons
      for discontinuation were failure to achieve a therapeutic effect, noncompliance,
      and adverse side effects. The findings of this naturalistic study represent a
      cautionary consideration for the remarkable enthusiasm that surrounded the
      introduction of risperidone.

PMID- 9550246
TI  - A syndrome of increased affect in response to risperidone among patients with
      schizophrenia.
AB  - Six of 13 outpatients with schizophrenia who participated in a ten-week open
      trial of risperidone had an initial good response to the medication followed by
      development of intolerable affect, including feelings of agitation and depression
      and periods of crying and insomnia. Patients who developed this syndrome did not
      differ from other patients in baseline ratings on the Brief Psychiatric Rating
      Scale (BPRS) and the Scale for the Assessment of Negative Symptoms, except that
      patients who developed the syndrome had a significantly higher mean baseline
      rating on the BPRS anxiety subscale. The authors suggest that risperidone may
      increase affect in patients with schizophrenia and that some patients, especially
      those with anxiety, may have difficulty managing the increase.

PMID- 9550247
TI  - Practices related to HIV risk assessment in general hospital psychiatric units in
      New York State.
AB  - Semistructured interviews including (questions about practices related to HIV
      risk assessment were conducted on 53 psychiatric units of general hospitals in
      New York State in 1992 and 1993. Few units have adopted practices across the
      board. Assessment of risk for many or almost all patients was reported by 25
      units (47 percent). On three units (6 percent) all patients received information
      about HIV, and on 13 (25 percent) many patients did. Twenty units (38 percent)
      reported counseling only a few patients about risk, and eight (15 percent)
      counseled almost none. Twenty-eight (53 percent) urged only a few patients to get
      an HIV test, and nine (17 percent) urged almost none.

PMID- 9550248
TI  - Effects of psychoeducational intervention for married patients with bipolar
      disorder and their spouses.
AB  - The relative benefit of adding a structured psychoeducational intervention to
      standard medication treatment for married patients with bipolar disorder and
      their spouses was assessed. Patients were randomly assigned to receive either
      medication management or medication management plus a marital intervention with
      their spouses for an 11-month period. Patients' symptoms, functioning, and
      adherence to their medication regimens were measured at study entry and at 11
      months. Significant effects favoring the combined treatments were observed for
      overall patient functioning but not for symptom levels. The marital intervention
      was associated with improved medication adherence. Combined psychosocial and
      medication treatment does not affect patients' symptom levels beyond the effects
      of medication alone, but it does result in significant incremental gains in
      overall patient functioning.

PMID- 9550249
TI  - Homelessness and mental illness in a professional- and peer-led cocaine treatment
      clinic.
AB  - The combined problems of substance abuse, mental illness, and homelessness among
      the urban poor represent a major public health issue. The study evaluated 340
      patients attending a cocaine day treatment program that integrates peer
      leadership and professional supervision. Thirty-six percent of the sample had a
      major mental illness, and 39 percent were homeless. Sixty-nine percent achieved
      an acceptable final urine toxicology status, and the median number of program
      visits was 46. Homelessness, a longer history of cocaine use, and a diagnosis of
      schizophrenia were associated with positive treatment outcomes. The results
      support the feasibility of a cocaine abuse treatment model combining professional
      and peer leadership.

PMID- 9550250
TI  - Denial of mental illness.

PMID- 9550251
TI  - Denial of mental illness.

PMID- 9550252
TI  - Primary physicians and adolescent health care.

PMID- 9550254
TI  - Rapidly growing employee assistance programs face major changes, more intense
      competition.

PMID- 9550253
TI  - New publication highlights intimate relationship between substance abuse and
      domestic violence.

PMID- 9550255
TI  - GAO study finds state psychiatric hospitals get biggest share of supplemental
      Medicaid payments.

PMID- 9550256
TI  - Treatment of a local recurrence of a carcinoid tumor of the middle ear by
      extended subtotal petrosectomy.
AB  - A recurrence of a primary carcinoid tumor of the middle ear 15 years after
      radical tympanomastoidectomy is reported. An extended subtotal petrosectomy using
      a craniocervical approach with temporary infracondylar mandibulotomy was
      performed, since imaging studies demonstrated an extensive tumor with a close
      relationship to the tegmen tympani, facial nerve, and ascending and horizontal
      portions of the carotid canal. The tumor was metabolically inactive.
      Histopathological examination showed a solid, trabecular tumor that was positive
      for pancytokeratin Lu5, neuron-specific enolase, pancreatic intestinal
      polypeptide and glucagon. Neuroendocrine-granules were demonstrable under
      electron microscopy. This case is reported to show that primary middle-ear
      carcinoid tumors can recur years after radical tympanomastoidectomy.

PMID- 9550257
TI  - An anomalous relationship of the descending portion of the facial canal to the
      jugular notch in the human temporal bone.

PMID- 9550258
TI  - A new epiglottoplasty procedure for the treatment of intractable aspiration.
AB  - Intractable aspiration may require diversion of the airway from the pharynx. The
      epiglottoplasty procedure involves suturing the epiglottis onto the perimeter of
      the larynx without creating resistance to the natural lines of force of the
      epiglottic cartilage. The procedure starts by an anterior subhyoid pharyngotomy.
      The epiglottis is released from the pre-epiglottic space and the thyroepiglottic
      ligament is sectioned. The disinsertion is completed in the laryngeal lumen by
      sectioning the epiglottis on each side by following its edges. The
      pharyngoepiglottic folds are preserved so as to serve as the rotational axis for
      the freed epiglottis. The petiole of the epiglottis is anchored to the posterior
      commissure and the free edge of the epiglottis above the ala and the angle of the
      thyroid cartilage, while the lateral sides of the suprahyoid epiglottis are
      sutured to the superior part of the arytenoids. This procedure was performed
      successfully in three patients with intractable aspiration.

PMID- 9550259
TI  - Feasibility of supracricoid laryngectomy based on pathological examination.
AB  - Partial horizontal supracricoid laryngectomy with cricohyoidopexy at the
      Department of Otolaryngology, Medical University of Bialystok, involves resection
      of the entire thyroid cartilage with the pre-epiglottic and paraglottic spaces.
      Experience has shown that this technique will permit adequate phonation,
      respiration and deglutition in selected advanced cases of supraglottic and
      glottic carcinoma. The purpose of this study was to verify histologically the
      indications for this surgery by examining sections of whole-organ laryngeal
      specimens. Post-laryngectomy specimens from 90 patients with otherwise previously
      untreated supraglottic (48), transglottic (22) and glottic (20) carcinomas were
      reviewed retrospectively. The majority (66) of the specimens were staged as pT4.
      Findings showed that 22 of the specimens analyzed (mostly supraglottic tumors)
      could have been eradicated by supracricoid laryngectomy alone. The present study
      confirmed the principles of supracricoid laryngectomy for selected large tumors.

PMID- 9550260
TI  - Argyrophilic nucleolar organizer region counts in squamous cell carcinomas of the
      head and neck after irradiation and chemotherapy.
AB  - After irradiation or chemotherapy of tumors of the head and neck, histological
      alterations might be difficult to assess. In 30 cases of squamous cell carcinomas
      of the pharynx, changes in argyrophilic nucleolar organizer region (AgNOR) counts
      were investigated after therapy. After treatment a significant decrease of AgNOR
      counts was detected (P < 0.001). No significant differences could be found
      between groups treated with radiotherapy, chemotherapy or a combination of
      radiotherapy and chemotherapy. These findings suggest that AgNOR counts might be
      useful to assess cytotoxic effects on a subcellular level.

PMID- 9550261
TI  - Acute vestibular dysfunction associated with interferon-alpha therapy.

PMID- 9550262
TI  - A proximal element within the human alpha 2(I) collagen (COL1A2) promoter,
      distinct from the tumor necrosis factor-alpha response element, mediates
      transcriptional repression by interferon-gamma.
AB  - Previous studies have shown that interferon-gamma (IFN-gamma) inhibits type I
      collagen gene expression through both transcriptional and post-transcriptional
      mechanisms (Kahari et al., 1990). In the present study, using transient cell
      transfections of human dermal fibroblast cultures with a series of 5' deletion
      promoter/CAT reporter gene constructs, we have identified the IFN-gamma-response
      element of the human alpha 2(I) collagen gene (COL1A2) promoter. Specifically, we
      have identified a segment of the proximal promoter region, located between
      nucleotides -161 and -125 relative to the transcription start site, as critical
      for down-regulation of COL1A2 promoter activity by IFN-gamma. This IFN-gamma
      response element (IgRE) is clearly distinct from the previously described tumor
      necrosis factor-alpha response element (TaRE) located between nucleotides -265
      and -241 of the COL1A2 promoter, a difference which is likely to explain the
      additive inhibitory effect of these two cytokines. The inhibitory effect of IFN
      gamma was dose-dependent and rapidly induced, requiring less than 5 min exposure
      of fibroblast cultures. Gel mobility shift assays indicated that a highly
      specific nuclear protein complex bound to this 37-base pair region of promoter.
      Competition experiments with oligonucleotides spanning discrete segments of this
      promoter region mapped the binding element within a distinctive pyrimidine-rich
      sequence. Point mutations within the latter revealed that this element plays a
      crucial role not only in the IFN-gamma response, but also in the basal activity
      of the proximal promoter. Substitution mutations within the IgRE of the -161/CAT
      construct attenuated the promoter response to IFN-gamma, as measured in transient
      cell transfections, and eliminated specific DNA/protein complex formation, as
      measured by gel mobility shift assay. UV-crosslinking experiments indicated that
      two DNA/protein complexes were formed with the IgRE, with molecular weights
      around 55 kDa and 30 kDa, corresponding to proteins of approximately 30 kDa and
      approximately 6 kDa, respectively. Our results further clarify the molecular
      mechanisms involved in the regulation of type I collagen gene expression by IFN
      gamma.

PMID- 9550263
TI  - Characterization of collagens and proteoglycans at the insertion of the human
      Achilles tendon.
AB  - This study provides a unique correlation between a molecular biological and
      biochemical analysis of the extracellular matrix (ECM) macromolecules in one half
      of 28 human Achilles tendons with an immunohistochemical study of the other. Both
      the insertion site and the mid-tendon were studied. The insertion (enthesis) is
      characterized by three distinctive fibrocartilages, two in the tendon (enthesial
      and sesamoid) and one on the heel bone (periosteal). Thus, its structure
      contrasts markedly with the fibrous character of the mid-tendon. RT-PCR analyses
      were performed on RNA extracted from mid-tendon and from the tendon
      fibrocartilages to investigate transcription of collagens and proteoglycans.
      Western blotting was also used to identify and characterize these macromolecules,
      and immunohistochemistry to localize their distribution. The results demonstrate
      striking differences in the ECM between the mid-tendon and its insertion. Types
      I, III, V and VI collagens, decorin, biglycan, fibromodulin and lumican were
      found in both the mid-tendon and the fibrocartilages, although their precise
      distribution often differed with site. mRNA for type II collagen was constantly
      present in the fibrocartilages, but it was only found in the mid-tendon of one
      specimen. The patterns of distribution for versican and aggrecan mRNA were
      complimentary - versican mRNA was present in the mid-tendon and absent from the
      fibrocartilages, while aggrecan mRNA was present in the fibrocartilages and
      absent from the mid-tendon. The range and distribution of ECM molecules detected
      in the Achilles tendon reflect the differing forces acting on it - the mid-tendon
      largely transmits tension and is characterized by molecules typical of fibrous
      tissues, but the fibrocartilages must also resist compression and thus contain,
      in addition, molecules typical of cartilage.

PMID- 9550264
TI  - Primary structure and expression of a chicken laminin beta chain: evidence for
      four beta chains in birds.
AB  - Characterization of a full length cDNA sequence for a chicken laminin beta chain
      is described which is most closely related to the mammalian beta 2 chain.
      Comparison with published sequences shows that the chicken beta 2-like chain
      corresponds to a fragment of a previously described laminin beta chain called B1
      2 (O'Rear, 1992). The sequence of the chicken beta 2-like chain differed from
      fragments of two other chicken laminin beta chains that were previously described
      and designated B1-1 (now called beta 1; O'Rear, 1992) and beta x (Ybot-Gonzalez
      et a1.,1995). In addition, the beta 2- like chain does not appear to be the
      chicken equivalent of the mammalian laminin beta 3 chain, since it differs
      markedly in cDNA sequence, possesses domain IV and has a transcript size of 6 kb.
      We therefore propose that there are at least four laminin beta chains in the
      chicken. Sequence comparison of the beta 2-like laminin chain with previously
      cloned beta 1 and beta 2 chains shows a somewhat closer relationship to rat and
      human beta 2 than to mouse and human beta 1, especially in domains I, II and
      alpha. In addition, two expressed fragments of the chicken beta 2-like chain were
      recognized by a monoclonal antibody (C4) regarded as specific for the rat beta 2
      chain (Hunter et al., 1989a). The results therefore suggest that the laminin
      chain previously described as a potentially novel chain called B1-2 (O'Rear,
      1992) is likely to be the chicken equivalent of the mammalian beta 2 chain.

PMID- 9550265
TI  - Overview of matrix metalloproteinase expression in cultured human cells.
AB  - The matrix metalloproteinases (MMP) have been implicated in tumor invasion and
      metastasis both by immunohistochemical studies and from the observation that
      specific metalloproteinase inhibitors block tumor invasion and metastasis.
      Oligonucleotide primers for thirteen MMPs (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP
      9, MMP-10, MMP-11, MMP-12, MMP-13, MMP-14, MMP-15, MMP-16) were optimized for use
      in RT-PCR. A semi-quantitative RT-PCR assay was used to determine the pattern of
      MMP mRNA expression in 84 normal and transformed or carcinogen transformed human
      cell lines and strains derived from different tissues. The results demonstrate
      one or more cell lines which express thirteen members of the MMP family. In
      addition, various oncogene transfected human fibroblast cell strains were
      analyzed for MMP expression. We confirm that over-expression of the H-ras
      oncoprotein correlates with up-regulation of MMP-9 and demonstrate that over
      expression of v-sis also up-regulates MMP-9. A cell line immortalized following
      myc expression was found to up-regulate MMP-7, MMP-11 and MMP-13. Inappropriate
      expression of several MMP mRNAs was detected in breast, prostate, bone, colon and
      oral tumor derived cell lines. Identification of at least one cell line
      expressing each of thirteen MMPs and the observation of oncogene induced
      expression of several MMPs should facilitate analysis of the transcriptional
      mechanisms controlling each MMP.

PMID- 9550266
TI  - Collagen IX: evidence for a structural association between NC4 domains in
      cartilage and a novel cleavage site in the alpha 1(IX) chain.
AB  - Collagen IX, a structural component of the extracellular matrix of connective
      tissues, is synthesized as long and short forms which contain or lack,
      respectively, a 27 kDa non-collagenous (NC) 4 domain at the N-terminus of the
      alpha 1(IX) chain of the molecule. The long form occurs in cartilage and
      developing cornea, but not in vitreous, suggesting a specialized function for the
      NC4 domain, perhaps by interacting with other macromolecules. To test this
      hypothesis, embryonic chick cartilage was treated with DTSSP, dissociated with
      bacterial collagenase, and the NC4-containing DTSSP-cross-linked protein
      complexes examined and purified. Analysis of cartilage extracts using an anti-NC4
      antibody, and of purified NC4-containing complexes, identified a predominant NC4
      dimer. A naturally-occurring N-terminal fragment of the alpha 1(IX) chain, whose
      size is equivalent to the NC4-COL3-NC3 domains of the chain, was identified.
      Association of collagen IX molecules via NC4 domains and the existence of a
      cleavage site close to the NC3 domain of the molecule are likely to be of primary
      importance in the growth and remodeling processes of cartilage, in health and
      disease.

PMID- 9550267
TI  - Molecular cloning and sequence analysis of the aggrecan interglobular domain from
      porcine, equine, bovine and ovine cartilage: comparison of proteinase-susceptible
      regions and sites of keratan sulfate substitution.
AB  - Oligonucleotide primers which were designed based on identical peptide sequences
      flanking the interglobular domain (IGD) of human, bovine and rat aggrecan were
      used in RT-PCR reactions containing human, porcine, equine, bovine and ovine
      cartilage RNA. Novel cDNAs encoding the IGD of the latter four species were
      obtained and sequenced. The deduced amino acid sequences for these cDNAs were
      aligned and compared with those described for six other species. Amino acid
      sequences surrounding the major proteolytic cleavage sites in the IGD are highly
      conserved, with some species-specific substitutions. Similarly, known sites of
      keratan sulfate attachment in the IGD are highly conserved in all species. The
      results provide essential amino acid sequence data for species commonly used in
      model systems of cartilage degeneration.

PMID- 9550268
TI  - Oro-palatal dysplasia Bettex-Graf--a new syndrome.
AB  - Four cases of an until now undescribed syndrome have been observed in Berne in
      the last 40 years. All four cases are members of the same family and have
      occurred in three consecutive generations. They present with a U-shaped palatal
      cleft, microstomia, hypoplasia of the mandibula and a partial anodontia. An
      autosomal dominant heredity was demonstrated. Karyograms have been made in three
      of the patients and in all patients showed an anomaly in the form of a "fragile
      site" in one chromosome (16 fra 16 [q22]). Surgical and orthopedic treatments
      were difficult.

PMID- 9550269
TI  - Balloon dilatation of oesophageal strictures in children.
AB  - During the last ten years balloon dilatation has become increasingly frequent in
      the therapy of oesophageal strictures, both for diagnosis and treatment. From
      1983 to 1994, balloon catheterization was performed in 36 children (oesophageal
      atresia 28, tracheo-oesophageal fistula 3, congenital stenosis 1, acquired
      oesophageal stricture subsequent to gastro-oesophageal reflux 1, to caustic
      ingestion 3). Age at treatment varied from 2 weeks to 15 years. Thirty-nine (3
      double) strictures were dilated a total of 171 times. Balloon dilatation was
      successful in 31 cases (79%). In two children therapy was changed to conventional
      bouginage and six strictures were resected. Advantages of the method may include
      that forces are exerted radially and that the procedure may be performed under
      better control since fluoroscopy is used.

PMID- 9550270
TI  - Ultrasonographic "triangular cord": the most definitive finding for noninvasive
      diagnosis of extrahepatic biliary atresia.
AB  - Early diagnosis of extrahepatic biliary atresia (EHBA) is very important for a
      successful bile drainage procedure. An urgent and extensive investigation is
      warranted to make a differential diagnosis of EHBA from other cholestatic
      disease, especially neonatal hepatitis (NH). The diagnosis may be made by
      laparotomy with cholangiogram and liver biopsy but these procedure are invasive.
      Because a cone-shaped fibrous tissue was always found at the porta hepatis during
      Kasai's procedure and that type of fibrous tissue has never been seen in other
      types of cholestatic jaundice, the authors have used ultrasonography (US) to
      detect fibrous remnants at the porta hepatis in infants clinically suspected of
      having EHBA and identified a triangular- or tubular-shaped echogenic density in
      the bifurcation of the portal vein at the porta hepatis in EHBA and called it an
      ultrasonographic "triangular cord (TC)". The authors determined that the presence
      of TC denoted the EHBA. On the other hand, nonvisualization of TC was interpreted
      as consistent with NH. In the present study, the authors reviewed
      ultrasonographic examination and hepatobiliary scintigraphy in a series of 41
      infants suspected of having EHBA or NH. The TC was identified in thirteen
      infants. In twelve of thirteen infants with TC found by US, the diagnosis of EHBA
      was confirmed at the time of Kasai's Roux-en-Y hepatoportojejunostomy operation.
      The remaining one died at 15 months of age without having treatment. TC was not
      visualized in 28 infants. Twenty-seven of 28 infants with absent TC improved
      clinically through medical treatment for NH. The other, diagnosed to have NH by
      needle and wedge liver biopsies, eventually showed a TC on follow-up US
      examination performed 40 days after the initial examinations. Moreover, follow-up
      percutaneous liver biopsy specimen showed typical findings of biliary atresia
      with bile duct proliferation and portal fibrosis. The patient underwent a Kasai
      hepatoportoenterostomy. On review of the hepatobiliary scintigraphy, all 13
      infants with TC had no intestinal excretion of isotope. Thirteen of 28 infants
      (46%) without TC also had no intestinal excretion of isotope in the 24hour follow
      up but all of them were confirmed to have NH by percutaneous liver biopsy and
      their subsequent clinical course confirmed NH with the detection of bile in their
      stool except one. On the basis of these results, the authors conclude that
      ultrasonographic TC is a very specific finding representing the fibrous cone at
      the porta hepatis and is a quick, simple, and definitive tool in the noninvasive
      diagnosis of EHBA. If TC is visualized, no further studies are necessary and
      exploratory-laparotomy can be done. If TC is not visualized, hepatobiliary
      scintigraphy is recommended to demonstrate bile duct patency. Percutaneous liver
      biopsy is only required if neither TC nor intestinal excretion of isotope is
      seen. However, early exploration or close US follow-up study is recommended in
      any patient suspected of having EHBA clinically, even if liver biopsy confirms
      the presence of NH.

PMID- 9550271
TI  - Thirty-eight years experience of malignant hepatic tumors in infants and
      childhood.
AB  - A description is given of therapeutic experiences with 39 cases of malignant
      liver tumors in infancy and childhood during the past 38 years. Of these
      patients, 9 not undergoing hepatic resection all died, while 18 (60%) of 30
      patients treated by hepatic resection survived. When only patients with
      hepatoblastoma are considered, 14 of 24 patients are alive, although 3 of them
      had local recurrence and had lung metastasis. Among patients with other types of
      liver tumor, those with hepatocellular carcinomas (2 cases) and vascular
      neoplasms all died in a short period of time, whereas 2 with yolk sac tumor and
      one with metabolic pancreatic tumor are alive despite of tumor recurrence. In
      summary, the results of surgical treatment of malignant liver tumors in infancy
      and childhood, which formerly were poor, have been improved remarkably, which we
      owe mainly to: 1) advances in diagnostic imaging techniques (e.g., angiography,
      ultrasonography, CT and MRI) permitting early diagnosis, localization of tumor,
      visualization of the coursing of major vessels (particularly, hepatic artery &
      vein) and more accurate definition of resectability, 2) technical improvement of
      hepatic resection and 3) progress of chemotherapy mainly with cisplatin and
      adriamycin.

PMID- 9550272
TI  - Spontaneous perforation of choledochal cyst: a study of 13 cases.
AB  - Of the 187 cases of infantile choledochal cyst treated at our hospitals, we
      encountered 13 with spontaneous perforation. All cases were under 4 years old.
      Eight cases were found to have biliary peritonitis and 5 had a sealed
      perforation. The shape of the extrahepatic bile duct was cystic in 8 and fusiform
      in 5. The cyst wall around the perforation was filmy and bile was found to be
      oozing through the thinned wall. Nine perforations were single while 4 cases had
      multiple perforations. Four of 17 perforations occurred in the posterior part of
      the cyst wall. Only 1 case of perforation was associated with protein plugs in a
      common channel, while 7 of the 10 cases of choledochal cyst requiring
      percutaneous biliary drainage due to signs of raised intrabiliary pressure were
      found to have protein plugs. We consider that spontaneous perforation of a
      choledochal cyst is not rare in infancy. The etiology of a perforation must be
      epithelial irritation of the biliary tract due to refluxed pancreatic juice
      caused by pancreatico-biliary malunion associated with mural immaturity due to
      infancy, rather than an abnormal rise in ductal pressure or congenital mural
      weakness at a certain point.

PMID- 9550273
TI  - Meckel's diverticulum and laparoscopy of children. What's new?
AB  - Laparoscopy has not changed the diagnostic approach in Meckel's diverticulum
      (MD). Preoperative echography and scintigraphy are still indicated in case of
      symptomatic diverticulum. During each submesocolic laparoscopy we must
      meticulously look for Meckel's diverticulum. There are two surgical procedures
      for MD resection: 1. Short intestinal resection after exteriorization (celio
      assisted surgery) is advocated in young patients or in complicated MD. 2.
      Laparoscopic resection by the Endo GIA stapler is advocated in older patients and
      latent MD with a narrow base.

PMID- 9550274
TI  - Sexuality and reproductive issues in children with myelomeningocele.
AB  - Recent advancements in surgical and medical therapies have improved the life
      expectancy of children with myelomeningocele. Yet, there has been a contrasting
      lack of improvement with regards to sexual function and reproductive issues that
      continue to infantilize this population. This article identifies five major risk
      factors that contribute to these delays which invariably lead to irreversible
      emotional trauma if they are not addressed early in childhood. Adequate
      psychosexual education of myelomeningocele patients and their families is a
      tremendous societal challenge. But, only with education will there be trends away
      from policies of isolation to those that reinforce community integration of the
      physically disabled.

PMID- 9550275
TI  - External fixation of lower limb fractures in children.
AB  - 26 children with 29 lower limb fractures, between the age of 2 and 15 years, were
      treated with an external fixator. The average time to union and removal of the
      fixator was 71 days for femoral and 73 days for tibial fractures. Complications
      included pin problems in nine cases, two devices had to be replaced with a cast
      and one refracture. Leg length discrepancies were noted in five children and
      radiological malalignment in three. We recommend external fixation for all
      femoral shaft fractures and all open or dislocated tibial and tibia and fibula
      fractures beginning at the age of three to adolescence.

PMID- 9550276
TI  - Hallux valgus in young patients: comparison of soft-tissue realignment and
      metatarsal osteotomy.
AB  - Two procedures of hallux valgus correction in young patients were compared by
      long-term results: soft-tissue realignment (McBride) and Mitchell osteotomy. From
      1970 to 1990, 33 hallux valgus deformities of 17 patients were corrected with one
      of these procedures at the Orthopaedic Department of the University of Mainz.
      Patients' age at operation ranged from 9 to 20 years and average follow-up was 16
      years later. Reevaluation consisted of subjective criteria, such as pain, shoe
      fitting, functional disability and cosmetics and objective parameters (hallux
      valgus and intermetatarsal angle, osteoarthrotic changes and range of motion of
      the metatarsophalangeal joint). They were assessed by report, interview,
      radiograph and physical examination and determined the overall outcome. McBride
      procedure showed 59% good, 12% satisfying and 29% dissatisfying long-term
      results, whereas outcome after Mitchell osteotomy was graded as good in 69%,
      satisfying in 12% and dissatisfying in 19% of the cases. Critical analysis
      emerged, that each procedure has its own bounds of indication. Successful hallux
      valgus correction can be achieved by an individual approach consisting of careful
      study of the indications, well-performed surgery and appropriate postoperative
      care.

PMID- 9550277
TI  - Cancrum oris (noma) in children.
AB  - Cancrum oris, noma or gangrenous stomatitis is a disease which affects primarily
      undernourished and immunosuppressed young children. Frequent in underdeveloped
      countries, it also is seen in rare cases of patients with AIDS and leukemia in
      America and in Europe. Once fatal, the disease is now better understood and today
      the repair of its terrible sequels is looked upon as a great surgical challenge.
      This paper reports a case of noma in a 3-year-old black African female admitted
      to this Service. In an already advanced stage of this illness with severe
      sequelae, she presented with partial amputation of the lips (upper and lower),
      right cheek, right side of the nose and maxilla. The choice of treatment of the
      infected area and eventual reconstruction is discussed.

PMID- 9550279
TI  - Abdominal situs inversus with congenital duodenal stenosis: rare association.
AB  - Abdominal situs inversus carries a significant mortality because the majority of
      cases (95 %) have associated cardiac and splenic defects. A review of all cases
      reported in the English literature confirms in addition the presence of
      significant gastro-intestinal pathologies, mainly annular pancreas, midgut
      volvulus and duodenal atresia. We report on an additional case of abdominal situs
      inversus without cardiac or splenic abnormalities, who had partial duodenal
      obstruction secondary to a mucosal diaphragm. This seems to be the thirteenth
      case associated with duodenal obstruction and the sixth case secondary to a
      mucosal duodenal diaphragm, to date, in this setting.

PMID- 9550278
TI  - A gastroschisis-like abdominal wall defect in the left hypochondrium. Case report
      and literature review.
AB  - Congenital abdominal wall defects are exceedingly rare on the left side. The
      presented patient had an upper abdominal wall defect located just lateral to the
      left rectus muscle. Additionally, upper parts of the abdominal flat muscles were
      defective on that side. Because no report was found in the literature about the
      defect described here, both its terminological and embryological backgrounds are
      discussed.

PMID- 9550280
TI  - Spleno-caval shunt in children using internal jugular vein graft: a case report.
AB  - Several techniques for decompression of portal hypertension have been described.
      The spleno-caval shunt is an easy and safe technique described in adult patients.
      However, the procedures described in adults are not adapted to children. We
      report an adaptation of this technique in a child, using the internal jugular
      vein as an interposition graft for relief of portal hypertension.

PMID- 9550281
TI  - Compression of the peroneal nerve by a cyst in a seven-year-old child.
AB  - Compressions of the peroneal nerve are rare since only some sixty such cases have
      been described since 1921. The authors report a new observation of compression
      extrinsic to the peroneal nerve by a synovial cyst, the source of which was the
      upper fibulo-tibial joint, in a child of seven years. As far as we know, this is
      the youngest age found in the relevant literature. Because of a swiftly appearing
      painful swelling, along with complete paralysis of the peroneal nerve, an
      electromyogram and a nuclear magnetic resonance were performed, with a view to
      confirming the diagnosis and to clarifying the topography of the cyst. The
      removal of the latter led to the child being cured with complete recovery of the
      peroneal nerve within three months.

PMID- 9550282
TI  - Effect of oral and intravenous insulin and glutamic acid decarboxylase in NOD
      mice.
AB  - Islet cell antigens have been administered orally and intravenously (I.V.) to NOD
      mice to assess their abilities to protect from or delay the onset of diabetes,
      and thereby provide insights that may have therapeutic implications in human
      trials. Whereas we and others have observed a delay in the onset of diabetes in
      NOD mice that have been fed with insulin from early life, we report here for the
      first time that feedings with porcine GAD65 alone (p = 0.226) or in combination
      with insulin (p = 0.011), have anti-diabetic effects in a prolonged study period
      (>400 days). While antigen-specific inhibitions of in vitro lymphocytic
      proliferation responses were seen (p < 0.05), antibody levels were unaffected by
      oral antigen treatments. IFN-gamma mRNA levels were downregulated in the islet
      infiltrates following oral antigen treatments while IL-2 and TNF-beta were
      expressed in all instances. We also observed that I.V. human recombinant GAD65,
      and porcine GAD given at weaning, delayed diabetes onset (p = 0.004) while
      similar treatments with a variety of inactive insulin preparations were generally
      ineffective. These findings thus indicate varying effects of oral and I.V.
      autoantigen administrations on the development of diabetes in NOD mice, and
      describe the immunological processes induced by oral autoantigen treatments.

PMID- 9550283
TI  - Interleukin-13 counteracts suppression induced by interleukin-1beta of glucose
      metabolism but not of insulin secretion in rat pancreatic islets.
AB  - The cytokine interleukin-1beta (IL-1beta) has been postulated to be involved in
      beta-cell destruction in IDDM. It has also been suggested that this action by IL
      1beta is mediated by nitric oxide (NO) generation. Recently it has been reported
      that Th2-cell promoting cytokines e.g. interleukin-4 (IL-4) and interleukin-13
      (IL-13) can reduce NO formation from activated macrophaghes after cytokine
      activation. In the present study we examined the effect of IL-13 on IL-1beta
      suppression of islet function. For this purpose rat pancreatic islets were
      cultured in medium RPMI 1640 + 10% fetal calf serum and exposed for 42 h to human
      IL-13 (0. 0.1, 1 and 10 ng/ml) in the presence or absence of human IL-1beta (25
      U/ml) during the last 24 h of culture. IL-13 alone did not affect any islet
      functions during prolonged exposure. The highest concentration of IL-13
      counteracted IL-1beta suppression of islet glucose oxidation, but not insulin
      release. Moreover, IL-13 failed to reduce IL-1beta stimulated NO production, as
      measured by medium nitrite levels. Acute exposure to IL-13 caused a slight
      stimulation of islet insulin secretion. When IL-4 (10 ng/ml) was combined with IL
      13 no synergistic action of the two cytokines was observed in the counteraction
      of IL-1beta mediated changes. In conclusion, the present study showed that IL-13
      could partially prevent IL-1beta induced inhibition of the glucose metabolism,
      and this effect appeared to be unrelated to NO levels. So far it has not been
      possible to demonstrate in vitro that Th2-cell promoting cytokines such as IL-4
      and IL-13 can effectively reduce cytokine-induced NO from islet cells, as has
      been reported for macrophages. However, it cannot be excluded that Th2-cell
      promoting cytokines can be effective in reducing a Th1-cell mediated anti-beta
      cell response in vivo.

PMID- 9550284
TI  - Administration of dehydroepiandrosterone sulfate retards onset but not
      progression of autoimmune disease in NZB/W mice.
AB  - NZB/W mice spontaneously develop an autoimmune disease characterized by the
      formation of anti-DNA antibodies and subsequent development of a fatal immune
      complex-mediated glomerulonephritis. Treatment of NZB/W F1 female mice with
      DHEAS, a precursor of DHEA, beginning at 2 months of age delayed the onset of
      autoimmune disease and prolonged survival. Animals treated with DHEAS beginning
      at 2 months of age had significantly lower anti-dsDNA serum antibody titers when
      compared to controls. Interestingly, DHEAS treatment had no effect on titers of
      anti-phosphatidylcholine (PtC) "natural" antibodies. Serum levels of IL-10, which
      increase with onset of disease, were also significantly reduced in mice treated
      with DHEAS beginning at 2 months of age. In contrast, if DHEAS treatment was
      started at 6 months of age, there was no effect on mortality rates. In addition,
      treatment of animals with DHEAS beginning at 6 months of age did not lower serum
      titers of anti-dsDNA and had no ameliorating effect on anti-PtC antibody
      production. Serum levels of IL-10 were also unaffected in mice treated with DHEAS
      beginning at 6 months of age. Together, these data suggest that parenteral
      administration of DHEAS is effective at delaying autoimmune disease and
      prolonging survival when given prior to the onset of symptoms. However, DHEAS
      treatment does not affect the course of disease when treatment begins after the
      onset of disease. We propose that DHEA(S) therapy used under similar conditions
      would not provide a clinically beneficial effect in the specific symptoms of
      immune complex-mediated glomerulonephritis.

PMID- 9550285
TI  - Effects of HgCl2 on the expression of autoimmune responses and disease in
      diabetes-prone (DP) BB rats.
AB  - Repeated exposure of Brown Norway (BN) rats to relatively low doses of HgCl2
      induces autoantibodies to renal antigens (e.g., laminin) and a membranous
      glomerulonephropathy characterized by proteinuria. In contrast, Lewis (LEW) rats
      are "resistant" to the autoimmune effects of mercury and, when exposed to this
      metal, are protected against experimental autoimmune encephalomyelitis (EAE) and
      Heymann's nephritis. To date, there is no information on "suppressive" effects of
      mercury in naturally occurring (so-called "spontaneous") rat models of autoimmune
      disease. Therefore, we have administered HgCl2 to diabetes-prone (DP) BB rats,
      animals that spontaneously develop both insulin-dependent diabetes mellitus
      (IDDM) and thyroiditis. We found that DP rats treated with mercury or water for a
      period of 40-125 days developed autoantibodies to thyroglobulin, with a higher
      incidence in HgCl2-injected animals (92% vs. 56% in H2O-injected controls). A
      novel finding of our study was the detection of autoantibodies to laminin in the
      same rats, again with an increased incidence after HgCl2 treatment (83% vs. 44%).
      IgG2a was the most frequently detected isotype of antibodies to laminin, followed
      by IgG1, IgG2b and IgG2c. The IgG isotype profile suggests that treatment with
      HgCl2 may activate both Th1 and Th2 lymphocytes in BB rats. In spite of these
      stimulatory effects on autoantibody responses, we found that there was no
      difference in the incidence of IDDM and thyroiditis between HgCl2-treated and
      control animals. We conclude that the suppressive effects of mercury previously
      observed in EAE and Heymann's nephritis of LEW rats do not occur in "spontaneous"
      autoimmune IDDM and thyroiditis of BB rats. Therefore, immune suppression caused
      by HgCl2 cannot be considered a common phenomenon, but may be a genetically
      determined characteristic of LEW rats, possibly related to a specific or unique
      cytokine profile of this particular rat strain. In contrast, while mercury does
      not seem to recruit, induce or rescue regulatory T cell function in DP rats, it
      does stimulate autoantibody responses in these animals.

PMID- 9550286
TI  - Anti-NGF autoantibodies and NGF in sera of Alzheimer patients and in normal
      subjects in relation to age.
AB  - It has been suggested that inflammation may be a possible cause of Alzheimer's
      disease (AD). Increased anti-NGF autoantibody levels and increased NGF frequency
      in serum have previously been associated with inflammatory responses. In this
      study no changes in anti-NGF autoantibody titers or in NGF frequency were
      detected in sera of AD patients, suggesting that they are not involved in the
      neuroimmunological mechanisms underlying AD. There were neither age-associated
      changes in NGF frequency in sera of four groups of normal subjects between 18-91
      years of age. In contrast, anti-NGF autoantibodies were significantly increased
      in sera of the 31-45 yr age group.

PMID- 9550287
TI  - Characterization of elevated neutrophil-associated IgG in various autoimmune
      disorders: not anti-neutrophil autoantibodies, but possibly immune complexes,
      bind to neutrophils.
AB  - Neutropenia is frequently observed in a variety of autoimmune disorders. As the
      mechanism of neutropenia in these disorders, the destruction of neutrophils by
      anti-neutrophil autoantibodies has been believed since elevated levels of
      neutrophil-associated IgG (NAIgG) have been described. However, no data exists to
      characterize the nature of NAIgG and show NAIgG is an anti-neutrophil
      autoantibodies. We investigated whether the elevated NAIgG in these patients
      consists of anti-neutrophil autoantibodies. The NAIgGs of 91 patients with
      autoimmune disorders including 50 patients with idiopathic thrombocytopenic
      purpura, 13 patients with systemic lupus erythematosus, 11 patients with
      Hashimoto's thyroiditis and 10 patients with Graves' disease were analyzed. The
      level of NAIgG was high in 36 of 91 patients. Elution studies were performed to
      determine whether NAIgG has a nature of autoantibodies. In model experiments, the
      ether eluate from neutrophils sensitized with neutrophil-specific alloantibody
      (anti-NA2) reacted with donor neutrophils, whereas the eluates from those with
      model immune complexes (ICs) failed. These data indicated that the ether elution
      technique is useful to determine whether NAIgG consists of anti-neutrophil
      autoantibodies. The NAIgG on patient's neutrophils was eluted with ether and the
      reactivity of the eluate with normal neutrophils was investigated. The eluates
      from 34 of 36 patients with various autoimmune disorders with elevated NAIgG
      level failed to react with donor neutrophils. These data indicated that the
      elevated NAIgG in the majority of these patients did not consist of anti
      neutrophil autoantibodies, but possibly of ICs.

PMID- 9550288
TI  - Effects of kinins on isolated stomachs of control and transgenic knockout B2
      receptor mice.
AB  - The aim of this study was to investigate the pharmacological profile of the kinin
      B1 and B2 receptors in isolated stomachs from wild-type control and B2 receptor
      knockout mice. Isometric contractions evoked by bradykinin (BK) (9 nM) and
      desArg9BK (28 nM) were shown to be different. The contraction induced by
      desArg9BK had a longer duration than that evoked by BK and increased during
      incubation in vitro in stomachs of wild-type controls, while in the transgenic B2
      receptor knockout mice, the contractions evoked by desArg9BK and BK were similar
      and followed the B1 receptor agonist pattern. BK but not the carboxypeptidase
      resistant analog, [Phe8psi(CH2-NH)Arg9]BK, was found to be active in the stomach
      of B2 receptor knockout mice. BK-induced contractions were prevented by mergetpa
      (a carboxypeptidase M inhibitor) (10 microM) and by a the B receptor antagonist,
      AcLys[DbetaNal7,Ile8]desArg9BK (R 715) (0.88 microM), while not being influenced
      by the B2 receptor antagonist HOE 140 (0.38 microM). BK and [Phe8psi(CH2
      NH)Arg9]BK were potent contractants of the wild-type mice stomach and their
      effects were not influenced by mergetpa or by the B receptor antagonist: they
      were reduced by HOE 140. After incubation in vitro for 3-4 hours, the tissues
      were treated with HOE 140 (4 microM) and FR-173657 (17 microM) to eliminate B2
      receptor function. In these tissues, BK evoked a B1-like contraction which was
      inhibited by mergetpa (10 microM) and antagonized by R 715 (8 microM). The
      results indicate that BK acts primarily on B2 receptors. However, after
      intramural conversion to desArg9BK, activation of B1 receptors of the mice
      stomach occurs. In the tissues of B2 receptor knockout mice, BK behaves as a pure
      B1 receptor agonist while in stomachs of control animals, the B2 receptor
      contribution is overwhelming. After complete blockade of the B2 receptor, BK is
      able to evoke B1-mediated responses similar to those observed in tissues of B2
      receptor knockout mice. It is concluded that the disruption of the B2 receptor
      gene eliminates the B2 receptor without influencing the B1 receptor system.

PMID- 9550289
TI  - Evidence for the involvement of multiple mechanisms in the excitatory action of
      bradykinin in the circular muscle of guinea-pig colon.
AB  - We have investigated, by using the sucrose gap technique, the mechanisms of the
      excitatory action of bradykinin in the circular muscle of the guinea-pig proximal
      colon. In the presence of atropine (1 microM) and S-ketoprofen (3 microM), the
      application of bradykinin (1 microM for 20 s) produced complex changes in
      membrane potential and muscle tension. The prevailing response was a small
      hyperpolarization followed by a slowly developing depolarization and a tonic
      contraction. The selective B2 receptor antagonist, HOE 140 (0.3 microM) blocked
      the responses to bradykinin (1 microM) while tetrodotoxin (0.3 microM) had no
      affect. The selective B1 receptor agonist, [des-Arg9]bradykinin (1 microM) did
      not affect the electrical or mechanical activities of the circular muscle. Apamin
      (0.1 microM) blocked the transient hyperpolarization and potentiated the
      bradykinin-induced depolarization and contraction. In the presence of apamin,
      nifedipine (1 microM) blocked spikes (when present) and the phasic contraction
      while leaving the tonic contraction unaffected. The excitatory action of
      bradykinin was further investigated in the presence of atropine (1 microM), S
      ketoprofen (3 microM), apamin (0.1 microM) and nifedipine (1 microM). The
      depolarization but not the contraction induced by bradykinin was reduced by about
      30% in low-Na+ (25 mM) but not in low Cl- (9.7 mM) Krebs solution. The
      depolarization and contraction evoked by bradykinin were reduced (by about 30 and
      75%, respectively) in Ca2+-free (2 min) Krebs solution. The blocker of the
      sarcoplasmic reticulum Ca2+ pump, cyclopiazonic acid (CPA, 10 microM) reduced the
      nifedipine-resistant depolarization and contraction induced by bradykinin by
      about 40 and 60%, respectively. The inhibitor of receptor-operated cation
      channels, SKF 96365 (50 microM) reduced the nifedipine-resistant bradykinin
      induced depolarization and contraction by about 40 and 30%, respectively, whereas
      the inhibitor of Ca2+-dependent chloride channels, niflumic acid (100 microM) was
      without effect. The inhibitory effect of SKF 96365 (50 microM) and CPA (10
      microM) was additive: in the presence of both drugs the bradykinin-induced
      depolarization and contraction were reduced by about 70-80%. The protein kinase C
      inhibitor, GF 109203x (10 microM) did not affect the nifedipine-resistant
      bradykinin-induced depolarization and contraction. At a concentration of 30
      microM, GF 109203x reduced the bradykinin-induced contraction by about 50% while
      leaving the bradykinin-induced depolarization unaffected. The KCl (40 mM)-induced
      contraction was significantly reduced (by about 30%) by GF 109203x (30 microM).
      The present findings indicate that, in the presence of apamin and nifedipine, the
      bradykinin-induced contraction of circular muscle of the guinea-pig colon is due
      to the influx of extracellular Ca2+ via non-selective cation channels and, in
      part, to the release of Ca2+ from a loosely bound internal store. Intracellular
      Ca2+ facilitates the bradykinin-induced depolarization, a response which does not
      involve a protein kinase C-dependent mechanism.

PMID- 9550290
TI  - Labelling of recombinant human and native rat serotonin 5-HT1A receptors by a
      novel, selective radioligand, [3H]-S 15535: definition of its binding profile
      using agonists, antagonists and inverse agonists.
AB  - The novel benzodioxopiperazine, 5-HT1A receptor weak partial agonist, S 15535 (4
      (benzodioxan-5-yl)1-(indan-2-yl)piperazine) bound with high affinity and
      selectivity to membranes of Chinese Hamster Ovary cells stably expressing the
      human (h) 5-HT1A receptor (Ki = 0.6 nM versus [3H]-8-hydroxy-dipropylamino
      tetralin, [3H]-8-OH-DPAT): its affinity at h5-HT1A receptors was more than 70
      fold higher than its affinity at > 50 other binding sites. S 15535 was tritiated
      to high specific activity (50 Ci/mmol) and its binding profile characterised. At
      22 degrees C, [3H]-S 15535 associated and dissociated from h5-HT1A receptors with
      half-times of 2.9 and 5.0 min, respectively, yielding a Kd estimate of 3.6 nM. In
      saturation binding experiments, [3H]-S 15535 displayed a Bmax value for h5-HT1A
      receptors (1630 fmol/mg), higher than that obtained with the agonist [3H]-8-OH
      DPAT (1023 pmol/mg). Guanylyl imidodiphosphate (GppNHp, 100 microM) reduced the
      binding of [3H]-S 15535 by only 25% compared with 79% for [3H]-8-OH-DPAT at h5
      HT1A receptors. [3H]-S 15535 also showed high affinity, saturable binding to rat
      hippocampal membranes (Bmax = 820 fmol/mg versus 647 fmol/mg for [3H]-8-OH-DPAT).
      For both h5-HT1A and rat 5-HT1A receptors, the Ki values for competition binding
      of 15 serotonergic ligands with [3H]-S 15535 was highly correlated with that of
      [3H]-8-OH-DPAT. However, important differences were also observed. The agonist, 5
      hydroxytryptamine (5-HT), displayed biphasic competition curves with [3H]-S 15535
      but not with [3H]-8-OH-DPAT at h5-HT1A receptors. Similarly, the 'antagonists',
      spiperone, methiothepin and (+)butaclamol, showed biphasic competition isotherms
      versus [3H]-S 15535 but not [3H]-8-OH-DPAT. When [3H]-S 15535 competition binding
      experiments were carried out in the presence of GppNHp (100 microM) the 5-HT and
      8-OH-DPAT competition curves shifted to the right, whereas the spiperone and
      methiothepin competition curves shifted to the left. In contrast, in the presence
      of GppNHp, the competition isotherms for N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-h exanecarboxamide (WAY 100,635) were not
      altered. Taken together, these data show that (i) [3H]-S 15535 is a highly
      selective 5-HT1A receptor ligand which labels both G-protein-coupled and
      uncoupled 5-HT1A receptors, (ii) antagonists, such as WAY 100,635, which yield
      monophasic isotherms in competition with both [3H]-agonists and [3H]-antagonists,
      are not sensitive to the G-protein coupling state of the receptor, but (iii)
      spiperone and methiothepin behaved as inverse agonists, their competition
      isotherms with [3H]-S 15535 being modulated in an opposite manner to those of
      agonists.

PMID- 9550291
TI  - In vitro studies of endogenous noradrenaline and NPY overflow from the rat
      hypothalamus during maturation and ageing.
AB  - Marked changes in brain monoamine content and NPY content occur during maturation
      and ageing. Earlier in vivo studies in our laboratory have reported blunted K+
      stimulated noradrenaline release and reduced NPY overflow in aged animals using
      microdialysis and push pull techniques. In this study, in vitro superfusion
      techniques were established to measure endogenous noradrenaline, NPY, DOPAC and 5
      HIAA overflow from the hypothalamus of 1, 5 and 16 month old Sprague-Dawley rats.
      A period of high K+ (56 mM) stimulation was carried out to elicit maximal
      release. Basal noradrenaline overflow was similar in all age groups of rats and
      during K+-induced depolarisation similar 3-4 fold increases were observed. On the
      other hand, basal and K+ stimulated NPY overflow were significantly greater in
      the adult rats compared to 1 month and 16 month old rats. Despite differences in
      absolute NPY overflow, the relative increase over resting was not significantly
      different across age groups. The molar quantities of hypothalamic NPY overflow at
      rest and under K+ stimulated conditions were three orders of magnitude lower than
      noradrenaline. Results of these studies suggest that both NPY and noradrenaline
      can be released from a similar hypothalamic pool. Basal and K+-evoked DOPAC and 5
      HIAA overflow were similar between the 3 age groups. Thus the overflow of
      hypothalamic noradrenaline, DOPAC and 5-HIAA under in vitro conditions was not
      altered from 1 to 16 months. In contrast, 5 month old rats had significantly
      higher NPY overflow than the other age groups (P < 0.05), consistent with a
      reported decline in NPY content with advanced age. Hypothalamic noradrenaline
      overflow was not affected by ageing, suggesting that a selective loss of NPY in
      the arcuo-PVN projection, or other projections to the hypothalamus with ageing
      may contribute to the reduction in NPY overflow in aged rats.

PMID- 9550292
TI  - Effects of pharmacological inhibition of glutamate-uptake on ischaemia-induced
      glutamate efflux and anoxic depolarization latency.
AB  - It has been proposed that deficient glutamate uptake, by increasing the
      extracellular concentration of this excitatory neurotransmitter, may contribute
      to the pathophysiology of cerebral ischaemia. This study aimed to examine whether
      pharmacological inhibition of glutamate uptake altered the kinetics of ischaemia
      induced glutamate efflux, and precipitated anoxic depolarisation. Microdialysis
      was used for application of the glutamate-uptake inhibitor L-trans-pyrrolidine
      2,4-dicarboxylate (L-trans-PDC), recording of the EEG and extracellular direct
      current (DC) potential with an electrode within the probe, and continuous
      monitoring of changes in extracellular glutamate. L-trans-PDC was applied locally
      from 8 min prior to cardiac arrest to the end of the recording period. L-trans
      PDC (2.5 mM) barely altered the time course of postmortem glutamate efflux in the
      cortex. Only the maximum rate of efflux during the first exocytotic phase, and
      the concentration reached at the end of this phase, appeared slightly increased.
      L-trans-PDC (5 mM) reduced significantly the delay between EEG silence and anoxic
      depolarization in the cerebral cortex (59.2 +/- 9.2 s vs. 79.7 +/- 11.5 s; n =
      6), but not in the striatum and hippocampus. These effects contrast with the
      marked increase in dialysate glutamate that L-trans-PDC produces in all these
      three brain regions. Together, these data do not support the hypothesis that
      inhibition of glutamate uptake plays a critical role, early in cerebral
      ischaemia. However, a contribution of reversed glutamate uptake to the secondary
      Ca2+-independent phase of ischaemia-induced glutamate efflux cannot be ruled out.

PMID- 9550293
TI  - H2 receptor-mediated facilitation and H3 receptor-mediated inhibition of
      noradrenaline release in the guinea-pig brain.
AB  - The effect of histamine and related drugs on the tritium overflow evoked
      electrically (0.3 Hz) or by introduction of Ca2+ ions into Ca2+-free K+-rich (25
      mmol/l) medium containing tetrodotoxin was studied in superfused guinea-pig brain
      cortex, cerebellum, hippocampus or hypothalamus slices and in mouse brain cortex
      slices preincubated with 3H-noradrenaline. The electrically evoked tritium
      overflow in guinea-pig cortex slices was inhibited by histamine; the H3 receptor
      antagonist clobenpropit reversed the effect of histamine to a slight
      facilitation. The facilitatory effect of histamine (obtained in the presence of
      clobenpropit) was not affected by the H1 receptor antagonist mepyramine but
      abolished by the H2 receptor antagonist ranitidine. In the absence of
      clobenpropit, ranitidine augmented the inhibitory effect of histamine. In slices
      superfused in the presence of ranitidine, the evoked overflow was inhibited by
      histamine and, more potently, by the H3 receptor agonist R-alpha-methylhistamine
      in a concentration-dependent manner (maximum inhibitory effect obtained for both
      agonists 30-35%). The concentration-response curve of histamine was shifted to
      the right by the H3 receptor antagonist thioperamide. R-alpha-methylhistamine
      inhibited the electrically evoked tritium overflow also in guinea-pig cerebellar,
      hippocampal and hypothalamic slices. In cortex slices superfused in the presence
      of clobenpropit, the H2 receptor agonists impromidine and, less potently, R
      sopromidine facilitated the evoked overflow in a concentration-dependent manner.
      S-Sopromidine only tended to increase the evoked overflow. The effect of
      impromidine was counteracted by the H2 receptor antagonists ranitidine and
      cimetidine. The extent of the maximum facilitatory effect of impromidine (by 15
      20%) was about the same when (i) the Ca2+ concentration in the medium was reduced
      from 1.3 to 0.98 mmol/l, (ii) the time of exposure to impromidine was reduced
      from 28 to 8 min or (iii) cerebellar, hippocampal or hypothalamic slices were
      used instead of cortical slices. The Ca2+-induced tritium overflow in guinea-pig
      cortex slices was inhibited by histamine (in the presence of ranitidine); this
      effect was abolished by clobenpropit. In slices superfused in the presence of
      clobenpropit, impromidine failed to facilitate the Ca2+-evoked tritium overflow.
      The electrically evoked tritium overflow in mouse brain cortex slices was
      inhibited by histamine by about 60% (both in the absence or presence of
      ranitidine). The inhibitory effect of histamine was abolished (but not reversed)
      by clobenpropit. In conclusion, noradrenaline release in the guinea-pig brain
      cortex is inhibited via presynaptic H3 receptors and facilitated via H2 receptors
      not located presynaptically. In the mouse brain cortex, only inhibitory H3
      receptors occur. The extent of the H3 receptor-mediated effect is more marked in
      the mouse than in the guinea-pig brain cortex.

PMID- 9550294
TI  - ATP release caused by bradykinin, substance P and histamine from intact and
      cultured smooth muscles of guinea-pig vas deferens.
AB  - Histamine (60 microM) produced ATP release from segments of guinea-pig vas
      deferens which was blocked by pyrilamine and triprolidine, H1-blockers, but not
      by ranitidine, an H2-blocker. The evoked-release was inhibited by the
      mitochondrial inhibitors, carbonyl cyanide-m-chlorophenylhydrazone (CCCP) and
      oligomycin. Bradykinin (BK) and substance P (SP) also caused substantial and
      moderate release of ATP, respectively. The BK-evoked release of ATP was inhibited
      by HOE140, a B2-antagonist, but not by [Des-Arg10] HOE140, a B1-antagonist. On
      the other hand, VIP, angiotensin II (AII) and cholecystokinin-octapeptide (CCK-8)
      failed to elicit a measurable release of ATP. Histamine and BK also enhanced the
      release of ATP from superfused cultured smooth muscle cells. These results
      suggest that ATP may be released as an autacoid from the smooth muscles in the
      presence of these chemical mediators.

PMID- 9550295
TI  - Depolarization evoked co-release of tachykinins from enteric nerves in the guinea
      pig proximal colon.
AB  - The aim of this study was to assess at which extent an even co-release of the
      tachykinins, substance P (SP) and neurokinin A (NKA), occurs from enteric
      neurons/nerves of the guinea-pig proximal colon during graded depolarization. In
      this preparation, a sharply diverging NK1/NK2 receptor pattern of tachykininergic
      co-transmission has been observed in physiological studies. The experiments were
      performed in capsaicin-pretreated (10 microM for 15 min) mucosa-free smooth
      muscle of guinea-pig proximal colon, to exclude the mucosa and the peripheral
      endings of primary afferent nerves as possible sources of released tachykinins.
      The content of extractable tachykinins was measured as SP- and NKA-like
      immunoreactivities (-LI) by radioimmunoassay. Chromatographic characterization of
      aqueous acetic acid extracts showed one peak of SP-LI corresponding to authentic
      SP, whereas there were multiple peaks of NKA-LI, the major one co-eluting with
      authentic NKA. An increased outflow of both SP- and NKA-LI was evenly produced in
      a concentration-dependent manner when the preparations were superfused with a
      high potassium (K) medium in which NaCl had been replaced with equimolar amounts
      (20-100 mM) of KCl. The high K-evoked release of SP- and NKA-LI was dependent
      upon the presence of extracellular calcium and was inhibited by about 50% in the
      presence of the N-type voltage-dependent calcium channel blocker, omega-conotoxin
      GVIA (0.1 microM). Omega-conotoxin MVIIC (1 microM), a non-selective blocker of N
      , P- and Q-type voltage-dependent calcium channels, likewise produced about 40%
      inhibition of evoked release of both peptides. No evidence for a role of L-type
      channels in tachykinin release was obtained, since the addition of nifedipine (1
      microM) or Bay K8644 (1 microM) did not significantly affect the response to high
      K. Neither NK1 receptor agonist (septide, 0.1 microM) or antagonist (SR 140333,
      10 nM) nor NK2 receptor agonists ([betaAla8]NKA(4-10) and GR 64349, 0.1 microM
      each) or antagonist (SR 48968, 10 nM) did affect the high K-evoked release of
      tachykinins. We conclude that SP and NKA are evenly co-released in response to
      graded depolarization of enteric nerves in the guinea-pig colon. Therefore, the
      specialization of tachykininergic transmission observed in functional studies
      does not originate at the prejunctional level. The co-release of tachykinins
      involves the influx of extracellular calcium via N-type but not L-type calcium
      channels. No evidence for the presence of NK1 or NK2 autoreceptors affecting
      tachykinin release from enteric neurons was obtained.

PMID- 9550296
TI  - A therapeutic dosage of amlodipine prevents vascular hyporeactivity induced in
      rats by lipopolysaccharide.
AB  - The aim of this work was to investigate whether treatment with the 1,4
      dihydropyridine Ca2+ antagonist amlodipine could affect the vascular
      hyporesponsiveness induced by cytokines. Endotoxemia was induced by Salmonella
      typhosa lipopolysaccharide (LPS) injection (4 mg kg(-1), i.p.). In endothelium
      denuded rings of thoracic aorta from untreated rats, contractile response to
      noradrenaline was decreased after LPS injection, this effect was partially
      overcome by the addition of N(omega)-nitro-L-arginine (L-NNA, 100 microM) into
      the bathing solution. In amlodipine-pretreated rats (15 mg kg(-1) day(-1),
      orally, for one week), the effect of LPS was lower than in untreated ones and it
      was completely reversed by L-NNA. The relaxation of the noradrenaline-induced
      tone evoked by L-arginine (10 microM) in aortae of LPS-injected rats was reduced
      in amlodipine-pretreated rats. Amlodipine-treatment reduced both the LPS-induced
      Ca2+-independent NOS activity in homogenates of heart and the expression of iNOS
      mRNA in aortae of LPS-injected rats. However, the vascular hyporeactivity induced
      by exposing aortae to interleukin-1beta in vitro was not influenced by amlodipine
      (10 nM). Amlodipine (10 microM) also did not affect the production of nitrite in
      primary aortic smooth muscle cell culture challenged by LPS although nitrite
      production in macrophage culture challenged with LPS was significantly inhibited.
      The results show that rat pretreatment with amlodipine prevented the decrease of
      vascular responsiveness induced by LPS, an effect that may be at least partly
      related to reduction of in vivo NOS induction. The weak effect of amlodipine on
      the in vitro NOS induction indicates that the protective action in endotoxemia
      did not result from a short term interaction with L-type Ca2+ channels in
      vascular smooth muscle. Alternative mechanisms are discussed.

PMID- 9550297
TI  - Inhibition by Compound II, a sotalol analogue, of delayed rectifier current (iK)
      in rabbit isolated sino-atrial node cells.
AB  - The effects of Compound II, a sotalol analogue, on spontaneous electrical
      activity and on three membrane currents (the delayed rectifier current, iK, the
      long-lasting inward calcium current, i(Ca,L) and hyperpolarization activated
      inward current, i(f)) were investigated in rabbit isolated sino-atrial node cells
      by whole cell clamp with amphotericin-permeabilised patches. A submaximal
      concentration of Compound II (50 nM) had a significant effect on the time and
      voltage dependent activation of iK and caused a positive shift of the iK
      activation curve. As well as blocking i(Kr), it caused some degree of block of
      i(Ks). Block of iK by Compound II was found to be concentration dependent with an
      IC50 of approximately 40 nM. 1 microM Compound II nearly completely blocked iK
      without significantly affecting the peak current or I/V relationships of i(Ca,L)
      or i(f). 50 nM Compound II caused a significant prolongation of APD100 and of
      cycle length. It also decreased diastolic depolarization rate without
      significantly affecting MDP and action potential amplitude. It is concluded that
      Compound II, a sotalol analogue, slows spontaneous activity of isolated rabbit SA
      node cells through a selective inhibition of iK.

PMID- 9550298
TI  - Effect of disopyramide on potassium currents in rabbit ventricular myocytes.
AB  - The effects of disopyramide (1-30 microM) on the 4-aminopyridine sensitive
      transient outward current (I(to)), on the rapid component of the delayed
      rectifier potassium current (I(Kr)) and on the inward rectifier potassium current
      (I(kl)) were studied in single rabbit ventricular myocytes at 35 degrees C by
      applying the whole-cell configuration of the patch clamp technique. Disopyramide
      significantly decreased the amplitude of I(to) (from 1510 +/- 122 pA at control
      to 1015 +/- 21 pA after 30 microM disopyramide at +50 mV; n = 5). This effect was
      not voltage- or use-dependent. Disopyramide (10 microM) influenced neither the
      recovery from inactivation of I(to) nor the steady-state inactivation curve. The
      drug dose dependently decreased the time constant of the fast component of the
      decay of I(to) (tau(f) = 6.41 +/- 0.25 ms, n = 24 for control; and 2.20 +/- 0.38
      ms, n = 5 after 30 microM disopyramide at +50 mV). The fractional block caused by
      30 microM disopyramide as a function of time was well fitted by a single
      exponential function with time constant of 1.48 +/- 0.18 ms (n = 5), most likely
      reflecting the binding kinetics of the drug to the open channel. The offset
      kinetics of the drug was estimated by using a double-pulse protocol and its time
      constant was 3.9 +/- 0.5 ms. Disopyramide (30 microM) did not influence
      significantly the onset of inactivation measured at -20 mV. The estimated EC50
      value for the I(to) block by disopyramide was 14.1 microM. Our results are
      consistent with an open-channel block of I(to) by disopyramide, however, a weak,
      drug-induced increase of the rate of inactivation and a moderate tonic block
      cannot be excluded. The amplitude of the outward tail current attributed to I(Kr)
      was depressed dose dependently by disopyramide (after clamping the cells back to
      the holding potential from +30 mV, 139.5 +/- 10.9 pA for control, and 30.7 +/-
      3.2 pA in the presence of 10 microM disopyramide; n = 11). The estimated EC50 was
      1.8 microM. I(to) is thus less sensitive to disopyramide than I(Kr). I(kl) was
      not influenced significantly by disopyramide, even when applied in the highest
      tested concentration (30 microM). It is concluded that in rabbit ventricular
      myocytes disopyramide blocks not only I(Kr), but also I(to), both of which may
      play an important role in the well established repolarization lengthening and
      antiarrhythmic effects of the drug.

PMID- 9550299
TI  - Effects of three peptidase inhibitors, amastatin, captopril and phosphoramidon,
      on the hydrolysis of [Met5]-enkephalin-Arg6-Phe7 and other opioid peptides.
AB  - The contents of [Met5]-enkephalin-Arg6-Phe7 (met-enk-RF) and its six hydrolysis
      products: Y, YG, YGG, YGGF, YGGFM, and YGGFMR were estimated after incubating met
      enk-RF with either a guinea-pig ileal or striatal membrane fraction for various
      times at 37 degrees C. After 45 min incubation with either ileal or striatal
      membranes, met-enk-RF was completely hydrolyzed, yielding Y as the major product.
      Incubation with either membrane preparation for 60 min in the presence of the
      aminopeptidase inhibitor amastatin hydrolyzed 90 or 92% of met-enk-RF,
      respectively, with YGG being the major product. If the dipeptidyl
      carboxypeptidase I inhibitor captopril is also included in the incubation, met
      enk-RF hydrolysis decreases by about half for both membranes, with YGG remaining
      the major product. Inclusion of three peptidase inhibitors, amastatin, captopril,
      and phosphoramidon (inhibition of endopeptidase-24.11) further reduced met-enk
      hydrolysis, with 87% or more remaining intact. This shows that met-enk-RF was
      mainly hydrolyzed by three enzymes, amastatin-sensitive aminopeptidase, captopril
      sensitive dipeptidyl carboxypeptidase I and phosphoramidon-sensitive
      endopeptidase-24.11, in both ileal and striatal membranes. Additionally,
      estimations of [Leu5]-enkephalin (leu-enk), alpha- and beta-neoendorphins (alpha-
      and beta-neoends), and dynorphin B (dyn B) contents after incubating the
      individual peptides with striatal membrane for 60 min in the presence of the
      three peptidase inhibitors showed that 98, 32, 5, and 23%, respectively, remained
      intact. Our previous studies together with the data obtained here show that one
      group of endogenous opioid peptides: met-enk, leu-enk, met-enk-RF, met-enk-RGL,
      and dyn A-(1-8) are largely or almost exclusively hydrolyzed by the three
      enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl
      carboxypeptidase I, and phosphoramidon-sensitive endopeptidase-24.11, and
      indicate that an unidentified fourth enzyme(s) is involved in the hydrolysis of
      another group of peptides: alpha-neoend, beta-neoend, and dyn B.

PMID- 9550300
TI  - Class I antiarrhythmic drugs alter the severity of myocardial stunning by
      modulating ATP-sensitive K+ channels in guinea pig ventricular muscles.
AB  - The effects of various class I antiarrhythmic drugs and glibenclamide were
      examined on the recovery of contraction during reperfusion, in relation to the
      action potential duration (APD) seen during ischemia. Action potential and
      contractile tension were recorded from isolated guinea pig right ventricular
      muscles perfused with oxygenated Tyrode solution via the coronary artery. Ten
      minutes of no-flow ischemia shortened the APD at 90% of repolarization level
      (APD90) to 58% of control (pre-ischemic values). The APD90 was completely
      restored after 60 min of reperfusion. The developed tension was abolished during
      ischemia and recovered to 87% of control after 60 min of reperfusion. In the
      presence of Vaughan Williams class Ia drug cibenzoline (5 microM) or an ATP
      sensitive potassium (K(ATP)) channel blocker glibenclamide (10 microM), the
      shortening of the APD90 during ischemia was significantly attenuated. However,
      the recovery of developed tension was significantly inhibited. Class Ic drug
      pilsicainide (10 microM) did not affect the ischemia-induced shortening of the
      APD90 or the recovery of developed tension after reperfusion. In the presence of
      class Ib drug mexiletine (10 microM), the shortening of the APD90 during ischemia
      was significantly facilitated. The recovery of developed tension in the presence
      of mexiletine tended to be improved, although the difference was not
      statistically significant. The developed tension measured after the 60 min
      reperfusion period following 20 min of no-flow ischemia was markedly depressed,
      indicating the presence of myocardial stunning. Mexiletine and pilsicainide
      significantly improved the recovery of developed tension and diminished the
      stunning. We conclude that cibenzoline and glibenclamide, which block cardiac
      K(ATP) channels inhibit contractile recovery after reperfusion by attenuating the
      shortening of APD during ischemia. In contrast, mexiletine, which activates
      K(ATP) channels (in addition to blockade of Na+ channels) improves contractile
      recovery by facilitating the shortening of APD during ischemia.

PMID- 9550301
TI  - Different inhibition patterns of tedisamil for fast and slowly inactivating
      transient outward current in rat ventricular myocytes.
AB  - Tedisamil has been described as a selective inhibitor of a fast inactivating
      transient outward current (i(to,f)) in rat ventricular myocytes. Because recent
      reports demonstrated the existence of a second slowly inactivating transient
      component (i(to,s)) we investigated i(to,s) and differentiated the effects of
      tedisamil on both transient outward current components and their influence on
      action potential duration. Standard electrophysiological techniques were used for
      whole cell recordings at 24-26 degrees C from enzymatically isolated myocytes.
      Inhibition of i(to,f) by tedisamil was the result of an acceleration of
      inactivation at positive test potentials with a concentration for half-maximal
      inhibition (EC50) of 4-7 micromol/l, which is confirmatory to reports from other
      investigators. Our new results show that i(to,s) is more sensitive to tedisamil
      with an EC50 of 0.5 micromol/l. Furthermore the pattern of i(to,s) inhibition is
      different compared with i(to,f), because inactivation of i(to,s) is not
      accelerated by tedisamil. Instead the amplitude of the steady state inactivation
      curve of i(to,s) is attenuated which indicates a reduction of maximally available
      current. I(to,s) was evaluated by three different methods as time-dependently
      inactivating current (7.5 s test pulse duration), voltage-dependently inactivated
      current and tedisamil-sensitive current. All approaches yield similar
      inactivation curves. The potential for halfmaximal inactivation of i(to,s) lies
      about 35 mV more negative than that for i(to,f) and the slope factor (K = -23 mV)
      is different to that of i(to,f) (K = -3 mV). Effectiveness of tedisamil-induced
      modulation of i(to,f) and i(to,s) on action potential repolarization was tested.
      Action potentials stimulated at 0.5 Hz were not prolonged by 1 micromol/l
      tedisamil (dominant i(to,s) block) at a repolarization level of 0 mV but
      prolonged to about 120% of control at -70 mV. This indicates that i(to,f) was
      sufficient to guarantee a regular early repolarization whereas decrease of
      i(to,s) delayed the final repolarization. In conclusion, the observation that
      tedisamil inhibits i(to,f) and i(to,s) differently supports the hypothesis that
      the two i(to)-components are related to two different channel populations
      expressed in rat ventricular myocytes.

PMID- 9550302
TI  - Inhibition by ethanol of excitatory amino acid receptors in rat locus coeruleus
      neurons in vitro.
AB  - Intracellular recordings were made in a pontine slice preparation of the rat
      brain containing the nucleus locus coeruleus (LC). In a first series of
      experiments, various parameters of spontaneous action potentials were evaluated.
      It turned out that ethanol (100 mM) does not alter the firing rate, the spike
      amplitude and the afterhyperpolarization following a spike. In subsequent
      experiments, the generation of action potentials was prevented by passing
      continuous hyperpolarizing current via the recording electrode. Under these
      conditions, ethanol (100 mM) had no effect on the membrane potential or input
      resistance. Pressure-applied N-methyl-D-aspartate (NMDA), (S)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and alpha,beta-methylene ATP
      (alpha,beta-meATP) reproducibly depolarized LC neurons. While ethanol (100 mM)
      depressed the NMDA- and AMPA-induced depolarization to a similar extent, it did
      not interact with alpha,beta-meATP. Lower concentrations of ethanol (10 and 30
      mM) had no effect on depolarizing responses to NMDA or AMPA. Noradrenaline
      applied by pressure pulses reproducibly hyperpolarized LC cells. These
      hyperpolarizations were unchanged by ethanol (100 mM). Biphasic synaptic
      potentials consisting of early depolarizing (PSP) and late hyperpolarizing (IPSP)
      components were evoked by electrical stimulation. Ethanol (100 mM) depressed the
      PSP and increased the IPSP. Glutamatergic PSPs recorded in the combined presence
      of picrotoxin (100 microM) and suramin (100 microM) were also inhibited by
      ethanol (100 mM). However, IPSPs recorded under these conditions were insensitive
      to ethanol (100 mM). In conclusion, ethanol may interfere with the AMPA (or NMDA)
      receptor-mediated fraction of the PSP and slightly facilitate the alpha2
      adrenoceptor-mediated fraction of the IPSP.

PMID- 9550303
TI  - Hypersusceptibility to DMCM-induced seizures during diazepam withdrawal in mice:
      evidence for upregulation of NMDA receptors.
AB  - The present study investigated the role of NMDA (N-methyl-D-aspartate) receptors
      in the hypersusceptibility to seizures induced by the benzodiazepine inverse
      agonist DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) during
      diazepam withdrawal in mice, using behavioral and biochemical approaches. The
      seizure threshold of DMCM was markedly decreased during diazepam withdrawal,
      reflecting withdrawal hyperexcitability in response to physical dependence. The
      decrease in the seizure threshold of DMCM in diazepam-withdrawn mice was
      inhibited by the non-competitive NMDA receptor antagonists MK-801 ((+)-5-methyl
      10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate; 50 microg/kg, s.c.)
      and ifenprodil (20 mg/kg, i.p.). The effective doses of these compounds were
      lower than those required to prevent DMCM-induced seizures in chronically vehicle
      treated mice. Since MK-801 and ifenprodil do not only bind to NMDA receptors but
      also to sigma receptors, the present study also investigated the effects of sigma
      receptor ligands. The decrease in the seizure threshold of DMCM in diazepam
      withdrawn mice was not modified by the sigma receptor agonist, (+)-pentazocine (5
      mg/kg, s.c.), or the sigma receptor antagonist, NE-100 (N,N-dipropyl-2-[4-methoxy
      3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride; 5 mg/kg, i.p.).
      Furthermore, the latency to the expression of wild running induced by
      intracerebroventricular administration of NMDA (60 ng/mouse) was also
      significantly lower in diazepam-withdrawn mice than in vehicle-treated control
      mice. On the other hand, there was no difference in the spermidine concentration
      between vehicle-treated control and diazepam-withdrawn mice. In a receptor
      binding experiment, the Bmax value for [3H]-MK-801 binding was significantly
      increased in cerebrocortical tissues from diazepam-withdrawn mice, while the Kd
      value did not change in either group. However, the acute addition of a high
      concentration of diazepam (10 and 100 microM) in vitro did not alter [3H]-MK-801
      binding in cerebrocortical membrane preparations. The behavioral experiments
      suggest that NMDA receptor antagonists may suppress benzodiazepine withdrawal
      responses, while the biochemical study reveals upregulation of the NMDA receptor,
      which may play an important role in the hypersusceptibility to DMCM-induced
      seizure in diazepam-withdrawn mice.

PMID- 9550304
TI  - Mitochondrial transmembrane potential and free radical production in excitotoxic
      neurodegeneration.
AB  - Excitotoxic cell death is involved in many forms of acute and chronic
      neurodegeneration. We induced excitotoxic cell death in cultured rat hippocampal
      neurons by brief exposure to two selective glutamate receptor agonists with
      different neurotoxic potencies, N-methyl-D-aspartate (NMDA) and kainate (KA).
      Digital video imaging was performed during exposure to the agonists to monitor
      free radical production and changes in mitochondrial transmembrane potential,
      psi(m). Brief exposure to NMDA (10 min) induced significant cell death in the
      hippocampal neurons reaching a maximum at a concentration of 300 microM (57.2+/
      2.6% cell death; P<0.001). In parallel imaging experiments we found that exposure
      to NMDA (300 microM, 10 min) induced a significant increase in superoxide
      production monitored with the oxidation-sensitive probe, hydroethidine (increase
      of 280+/-33% above baseline; P<0.001). Rhodamine-123-based imaging revealed a
      loss of psi(m) in 70.1+/-10.1 % of the hippocampal neurons during the exposure to
      NMDA. In contrast to NMDA, brief exposure to KA (10 min) produced limited
      neurotoxicity reaching a maximum at a concentration of 100 microM (10.2+/-4.0%
      cell death; P<0.05). Exposure to KA (100 microM, 10 min) also caused a
      significant increase in superoxide production. This increase, however, was
      significantly less pronounced than that produced by NMDA (increase of 94+/-17%
      above baseline; P<0.001 compared to controls or NMDA-exposed cultures). Moreover,
      rhodamine-123-based imaging revealed that KA (100 microM) caused a collapse of
      psi(m) in only 13.5+/-1.4% of the hippocampal neurons. In conclusion, the present
      study demonstrates that early changes in intracellular superoxide production and
      psi(m) relate to neuronal survival outcome in excitotoxic cell death.

PMID- 9550305
TI  - Influence of Clostridium botulinum C2 toxin on Fc epsilonRI-mediated secretion
      and tyrosine phosphorylation in RBL cells.
AB  - We studied the effects of the binary Clostridium botulinum C2 toxin on stimulated
      [3H]serotonin release and protein tyrosine phosphorylation in RBL 2H3 hm1 cells.
      Actin was specifically ADP-ribosylated by C2 toxin in intact cells resulting in a
      2-3 fold increase in antigen- or calcium ionophore (A23187)-induced
      degranulation. The effects of C2 toxin were time- and concentration-dependent.
      Toxin treatment, which dramatically changes the morphology of RBL cells, was not
      sufficient to induce mediator release in the absence of activators of secretion.
      Antigen- and A23187-stimulated tyrosine phosphorylation of 60-80 kDa and 110-120
      kDa proteins was reduced or blocked after C2 toxin incubation. Treatment of RBL
      cells with the tyrosine phosphatase inhibitor pervanadate reversed the inhibitory
      effect of C2 toxin on stimulated protein tyrosine phosphorylation indicating
      activation of phosphatases by C2 toxin. The data indicate that disassembly of the
      actin cytoskeleton by C2 toxin facilitates Fc epsilonRI-mediated signal-secretion
      coupling and suggest a role of the actin cytoskeleton in phosphatase regulation
      in RBL cells.

PMID- 9550306
TI  - Ocular pharmacokinetics of verapamil in rabbits.
AB  - Previously, it had been demonstrated that cataract in diabetic rats can be
      prevented by systemical administration of the calcium channel blocker verapamil.
      In addition to that, 0.125% verapamil eye drops were found to significantly
      reduce the intraocular pressure in ocular hypertensive human subjects. The
      purpose of this study was to investigate the ocular penetration and elimination
      of verapamil after topical administration of the drug in rabbits. Two drops of a
      0.125% aqueous solution of RS-verapamil hydrochloride (corresponding to a total
      dose of 125 microg RS-verapamil hydrochloride) were administered into the
      conjunctival sac. Aqueous humor and blood samples were taken at different times
      after administration and analysed for drug concentration by combined gas
      chromatography-mass spectroscopy. Following the instillation of 0.125% verapamil
      eye drops in a total dose of 125 microg RS-verapamil, mean (+/- SEM) aqueous
      humor peak levels of 1607 +/- 272 ng/ml were achieved after 20 min. Mean half
      life for the elimination from the aqueous humor was 33 min. Topical application
      of verapamil produced very low serum peak concentrations (10.5 +/- 1.3 ng/ml).
      The results of our study demonstrate that topically administered verapamil
      readily penetrates into the anterior chamber leading to aqueous humor drug levels
      in the microM range without producing serum levels that are high enough to cause
      cardiovascular side effects.

PMID- 9550307
TI  - Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated
      rat lung and liver.
AB  - The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) is a strong lung carcinogen in all species tested. To elicit its
      tumorigenic effects NNK requires metabolic activation which is supposed to take
      place via alpha-hydroxylation, whereas N-oxidation is suggested to be a
      detoxification pathway. The differences in the organ specific metabolism of NNK
      may be crucial for the organotropy in NNK-induced carcinogenesis. Therefore,
      metabolism of NNK was investigated in the target organ lung and in liver of
      Fischer 344 (F344) rats using the model of isolated perfused organs. High
      activity to metabolize 35 nM [5-3H]NNK was observed in both perfused organs. NNK
      was eliminated by liver substantially faster (clearance 6.9 +/- 1.6 ml/min, half
      life 14.6 +/- 1.2 min) than by lung (clearance 2.1 +/- 0.5 ml/min, half-life 47.9
      +/- 7.4 min). When the clearance is calculated for a gram of organ or for
      metabolically active cell forms, the risk with respect to carcinogenic mechanisms
      was higher in lung than in liver. The metabolism of NNK in liver yielded the two
      products of NNK alpha-hydroxylation, the 4-oxo-4-(3-pyridyl)-butyric acid (keto
      acid) and 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid). In lung, the major
      metabolite of NNK was 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK
      N-oxide). Substantial amounts of metabolites formed from methyl hydroxylation of
      NNK, which is one of the two possible pathways of alpha-hydroxylation, were
      detected in lung but not in liver perfusion. Formation of these metabolites (4
      oxo-4-(3-pyridyl)-butanol (keto alcohol), and 4-hydroxy-4-(3-pyridyl)-butanol
      (diol) can give rise to pyridyloxobutylating of DNA. When isolated rat livers
      were perfused with 150 microM NNK, equal to a dosage which is sufficient to
      induce liver tumors in rat, glucuronidation of 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol (NNAL) was increased when compared to the concentration of 35
      nM NNK. Nevertheless, the main part of NNK was also transformed via alpha
      hydroxylation for this high concentration of NNK.

PMID- 9550308
TI  - Effect of nicotine or cotinine on metabolism of 4-methylnitrosamino-1-(3-pyridyl)
      1-butanone (NNK) in isolated rat lung and liver.
AB  - The scope of the present study was to investigate whether nicotine or cotinine
      will affect the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) in isolated perfused rat lungs and livers and to study the effect of
      starvation on pulmonary metabolism of NNK. NNK metabolism was investigated in
      isolated perfused liver and lung of male F344 rats perfused with 35 nM [5-3H]NNK
      in presence of a 1400-fold excess of the main tobacco alkaloid nicotine and its
      metabolite cotinine. In perfused rat livers, nicotine and cotinine inhibited NNK
      elimination and metabolism and led to a substantial increase of elimination half
      life from 14.6 min in controls to 25.5 min after nicotine and 36.6 min after
      cotinine co-administration, respectively. In parallel, the pattern of NNK
      metabolites was changed by nicotine and cotinine. The pathway of alpha
      hydroxylation representing the metabolic activation of NNK was decreased to 77%
      and 85% of control values, whereas N-oxidation of NNK and glucuronidation of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased 2.6- and 1.2
      fold in presence of nicotine and cotinine, respectively. When isolated rat lungs
      were perfused with 35 nM NNK for 3 h neither the elimination nor the pattern of
      metabolites were substantially affected due to co-administration of 50 microM
      nicotine or cotinine. Cytochrome P450 2E1 is known to participate in the
      activation of NNK and can be induced by starvation. However, isolated rat lungs
      from male Sprague Dawley rats perfused with [1-14C]NNK at about 2 microM for 3 h,
      revealed only small differences in pulmonary elimination and pattern of NNK
      metabolites between fed and starved animals. These results suggest that nicotine
      and its main metabolite cotinine inhibit the metabolic activation of NNK
      predominantly in the liver whereas activation in lung, a main target organ of NNK
      induced carcinogenesis, remained almost unaffected.

PMID- 9550309
TI  - Isothiocyanatobenzyl imidazoline is an alkylating agent for I2-imidazoline
      binding sites in rat and rabbit tissues.
AB  - Isothiocyanatobenzyl imidazoline (IBI), the 4'-NCS analogue of tolazoline, has
      been used to alkylate several receptor sites in rabbit iris muscles. Because of
      the high affinity of tolazoline for the I2-imidazoline binding sites (Ki = 16-130
      nM), this study was designed to assess whether IBI is also an alkylating agent
      for these sites. In competition studies, IBI displayed moderate affinity (Ki
      approximately 2-3 microM) against I2A-imidazoline sites in the rabbit cerebral
      cortex and I2B-imidazoline sites in the rat cerebral cortex labelled by [3H]2-(2
      benzofuranyl)-2-imidazoline ([3H]2-BFI). However, preincubation (30 min at 25
      degrees C) of rat cortical and liver membranes with IBI (10(-7) M to 10(-3) M),
      followed by extensive washing, markedly decreased (17% to 96%) the specific
      binding of [3H]2-BFI to I2B-imidazoline sites. IBI (10(-5) M to 10(-3) M) also
      bound irreversibly to I2A-imidazoline sites in rabbit cerebral cortex but with a
      lesser efficacy (27% to 83% reduction of [3H]2-BFI binding). Saturation curves of
      [3H]2-BFI binding in the rat cerebral cortex indicated that preincubation with
      10(-6) M IBI reduced the total density (Bmax) without affecting the affinity (Kd)
      of I2B-imidazoline sites for IBI. Acute treatments (6 h) with IBI (10 and 30
      mg/kg, i.p.) also dose-dependently reduced (26% and 41%; respectively) the total
      density of I2B-imidazoline sites. These results demonstrate the ability of IBI to
      alkylate I2-imidazoline binding sites in vitro and in vivo and provide evidence
      for the use of IBI as a new tool for the study of the functional implications of
      imidazoline binding sites.

PMID- 9550310
TI  - Unusual expression of S-100 protein in histiocytic neoplasms.
AB  - Twenty-nine cases of histiocytic neoplasms, some resembling juvenile
      xanthogranuloma (JXG) and others resembling reticulohistiocytoma (RH), were
      evaluated. Immunohistochemical stains were performed. In this series, seven cases
      were identified that expressed S-100 protein positive cells. The S-100 positive
      cells were predominantly large mononuclear and multinucleated histiocytes with
      eosinophilic cytoplasm, but also in some cases xanthomatous cells and Touton
      giant cells. These cells also expressed a positive reaction for vimentin, KP-1,
      and Factor XIIIa. There was no reactivity observed for monoclonal antibody
      010(CD1a). A positive reaction for S-100 protein is conventionally accepted as a
      useful differentiating feature between histiocytosis X and non-X histiocytosis
      such as JXG and RH. The conflicting results of the immunohistochemical stains in
      the lesions we studied could be potential pitfalls in diagnosing histiocytic
      neoplasms.

PMID- 9550311
TI  - Apoptosis and cellular proliferation in human epidermal squamous cell neoplasia.
AB  - We examined cell loss (apoptosis) and proliferation in a histopathological
      spectrum of epidermal squamous cell neoplasia, including 11 cases of solar
      keratosis (SK), 18 Bowen's diseases (BD) and 19 invasive squamous cell carcinomas
      (SCC). Apoptotic and proliferative cells were determined by terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling
      (TUNEL) and by the detection of nuclear antigen Ki-67, respectively. Few
      apoptotic cells were observed in normal epidermis, while TUNEL index (TI;
      percentage of TUNEL-positive cells) was highest for SCCs, followed by BDs and
      SKs, in the order given. Although the mean Ki-67 index did not differ between
      SCCs and BDs, both disease types showed a significantly higher index than the
      SKs. Of SCCs, both TI and Ki-67 index values were significantly higher in poorly
      than in well differentiated carcinomas. TI was significantly higher in SCCs
      without P53 immunohistochemical expression than in SCCs with P53 expression,
      while TI and Ki-67 indices did not correlate with P53 expression in the SKs and
      BDs. These results suggest that apoptosis reflects not only cell loss, but also
      proliferative activity in the epidermal neoplastic lesions.

PMID- 9550312
TI  - Differential expression of connective tissue growth factor gene in cutaneous
      fibrohistiocytic and vascular tumors.
AB  - Connective tissue growth factor (CTGF) is a member of a family of immediate early
      gene products that may play an important role during tissue regeneration, wound
      repair and skin fibrosis. In this study, CTGF gene expression in mesenchymal
      tumors was investigated by in situ hybridization and CD34 antigen expression was
      studied by means of immunohistochemical staining. CTGF mRNA was expressed in
      fibroblasts of all nine dermatofibromas examined, but five of seven
      dermatofibrosarcoma protuberans (DFSP) or two cases of malignant fibrous
      histiocytoma were negative for its expression. In contrast, CD34 antigen was
      expressed only in DFSP. In vascular tumors, CTGF mRNA was expressed in pyogenic
      granuloma but not in angiosarcoma. In addition, the endothelial cells in
      angiolipoma and angioleiomyoma, but not in venous lake, expressed CTGF mRNA.
      These vascular lesions were all positive for CD34 expression. Tumors of other
      origins were negative for CTGF mRNA. Our findings indicated that benign
      fibroblasts and/or vascular endothelial cells have the capability to express CTGF
      mRNA when activated, but these cells lose this ability when they achieve
      malignant potency. Thus, examination of CTGF gene expression may be useful for
      differentiating between benign and malignant mesenchymal tumors, or to determine
      the origin of the tumors in connective tissue.

PMID- 9550313
TI  - Atypical decubital fibroplasia: a series of three cases.
AB  - We report three cases of atypical decubital fibroplasia (ADF), a benign, reactive
      pathologic process that develops in the skin and subcutaneous tissue of
      immobilized or debilitated patients. Two patients were immobilized, one
      wheelchair bound, and one bedridden. The third patient frequently lay over the
      affected area. Two were male, one female, ages 49, 66, and 89 (mean 68 years
      old). Each patient presented with a subcutaneous mass, one with focal surface
      ulceration, present for 5 months, 6 months, and 12 months (mean 7.7 months). The
      locations included back, lateral thigh (over greater trochanter), and lateral
      chest wall. No other lesions were present, and none had recurrences.
      Histologically, atypical decubital fibroplasia is characterized principally by
      dermal and subcutaneous tissue involvement with fibrinoid necrosis, reactive
      fibrosis, and focal myxoid change with surrounding more cellular zones of
      prominent reactive neovascularization including granulation tissue and ectatic
      vessels with reactive atypical fibroblasts and fat necrosis. Other findings
      include hyalinization of vessel walls, fibrin thrombi, red blood cell
      extravasation, hemosiderin deposition, and acute and chronic inflammation.
      Although the changes are predominantly deep, involving the dermis, subcutaneous
      tissue and skeletal muscle, the overlying epidermis may ulcerate. Recognition of
      atypical decubital fibroplasia is of paramount importance, for it may be
      misinterpreted as a sarcoma, both clinically and histologically.

PMID- 9550314
TI  - Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell
      carcinoma, and trichoepithelioma in small cutaneous biopsy specimens.
AB  - The distinction between squamoid basal cell carcinoma and basaloid squamous cell
      carcinoma (or between BCC and trichoepithelioma variants) is usually made readily
      on the basis of defined histological criteria. However, these differential
      diagnoses occasionally can pose difficult morphological problems. The stated
      distinctions are clinically important because the risk of progressive disease is
      significantly higher with squamous carcinoma of the skin than with basal cell
      carcinoma (BCC), and a trichoepithelioma misinterpreted as BCC burdens the
      patient with an inaccurate diagnosis that may result in inappropriate surgery.
      Recent reports have suggested that reactivity with the monoclonal antibody Ber
      EP4 is capable of separating histologically similar basal cell and squamous
      carcinomas, and that the expression of bcl-2 or CD34 antigen is able to
      distinguish BCC from trichoepithelioma. However, corroborative studies of these
      contentions are few in number. In order to investigate the usefulness of the
      stated immunostains in the above-cited differential diagnoses, the authors
      analyzed 45 basal cell carcinomas and 22 squamous carcinomas, as well as 36
      trichoepitheliomas. The monoclonal antibodies Ber-EP4, My10 (CD34), and anti-bcl
      2 were applied to formalin-fixed paraffin sections in all cases, using a standard
      avidin-biotin-peroxidase complex method. Most BCCs demonstrated strong, diffuse
      cytoplasmic labeling with Ber-EP4 and anti-bcl-2. In contrast, the squamous
      carcinomas were uniformly negative for the former marker and only focally
      reactive for the latter in four examples. 'Peripheral' bcl-2 staining of
      trichoepitheliomas was noted in 24 of 33 of the immunoreactive tumors, but the
      remainder were marked diffusely and similarly to most BCCs. Among the latter,
      immature trichoepitheliomas were diffusely reactive for this marker in 6 of 8
      cases. Labeling of epithelium for CD34 failed to discriminate between any of the
      tumor types under evaluation, whereas staining of peritumoral stroma was
      characteristic of the majority of trichoepitheliomas and more than one-third of
      metatypical basal cell carcinomas. These data support the suggestion that Ber-EP4
      and bcl-2 are useful in the separation of BCC from squamous carcinomas.
      Nevertheless, they also serve to caution against reliance upon bcl-2 and CD34
      immunostains in attempting to distinguish BCC from trichoepithelioma in
      histologically enigmatic cases. There is currently no certain method other than
      conventional microscopy that can be applied successfully to the latter problem.

PMID- 9550315
TI  - Cutaneous infiltrate of chronic lymphocytic leukemia and relationship to primary
      cutaneous epithelial neoplasms.
AB  - Chronic lymphocytic leukemia involves the skin in a small percentage of patients
      and may portend an ominous prognosis in some patients. We report a series of
      eight biopsies from seven different patients in which the cutaneous leukemic
      infiltrate was confined exclusively to the region immediately surrounding primary
      epithelial neoplasms including squamous cell carcinoma (6), basal cell carcinoma
      (1) and actinic keratosis (1). The malignant lymphocytes appear to constitute a
      host response to these neoplasms and do not appear to suggest a rapid downhill
      course for these patients. These observations serve to 1) suggest a new pattern
      of cutaneous involvement by leukemic cells and 2) offer some insights into
      potential cellular trafficking patterns of these neoplastic cells.

PMID- 9550316
TI  - Detection of human papillomavirus in verrucous carcinoma from HIV-seropositive
      patients.
AB  - Anogenital squamous cell carcinoma has been noted with increased frequency in HIV
      seropositive patients. Verrucous carcinoma is a variant of squamous cell
      carcinoma that tends to be locally invasive and non-metastasizing. Although human
      papillomavirus (HPV) has been strongly implicated in other squamous neoplasms, it
      has been variably associated with verrucous carcinoma and has not been examined
      in these lesions in the HIV-positive population. The aim of this study was to
      examine the association of HPV with anal verrucous carcinoma in patients with the
      human immunodeficiency virus (HIV). HPV DNA in situ hybridization for HPV Types
      6/11, 16/18, and 31/33/35 was performed on formalin-fixed, paraffin-embedded
      tissue from six cases of verrucous carcinoma and four cases of condyloma
      acuminatum in perianal specimens from HIV-seropositive patients. HPV DNA
      sequences were identified in five of six cases of verrucous carcinoma and in all
      cases of condyloma acuminatum. Of the five verrucous carcinomas that harbored
      detectable HPV DNA, four contained HPV 6/11 and two contained HPV 16/18. One
      contained both HPV 6/11 and HPV 16/18. All four cases of condyloma acuminatum
      were positive for HPV 6/11. One patient included in this series had three
      chronologically separate verrucous carcinomas. The initial lesion was negative
      for HPV DNA. Subsequent verrucous carcinomas were positive for HPV type 6/11 and
      type 16/18, respectively. The data presented support the concept that verrucous
      carcinoma in the HIV-seropositive population is associated with HPV, which may
      indeed play an important role in its pathogenesis.

PMID- 9550317
TI  - Utility of deeper sections and special stains for dermatopathology specimens.
AB  - Special (non-hematoxylin and eosin) stains and deeper sections are routinely used
      in dermathopathology, although their utility has not been well established. All
      cases requiring special stains or deeper sections over a three-month period were
      reviewed to see how often these additional studies contributed to accurate
      diagnosis. In our series, deeper sections provided diagnostic information to the
      pathologist in 37.3% [95% confidence interval (CI) 28-46%] of the cases in which
      they were performed. Deeper sections are more likely to provide a more accurate
      diagnosis (23.6%, 95% CI 16-32%) rather than establish a new diagnosis not seen
      on the original sections (13.6%, 95% CI 7-20%). Their use is especially helpful
      in assessing the presence or absence of cutaneous malignancy rather than in
      diagnosing inflammatory skin processes. Special stains contributed to the
      diagnosis in 21.1% (95% CI 11-32%) of cases. When special stains were performed
      to diagnose an infection they were effective in 14.7% (95% CI 6-24%) of the
      cases. When special stains were performed to diagnose any other pathologic
      processes (neoplasm, inflammation, collagen vascular disease, and amyloid) they
      were effective in 31.8% (95% CI 24-44%) of the cases.

PMID- 9550318
TI  - Signet-ring squamous cell carcinoma: a case report.
AB  - A-50-year-old Hispanic man presented to the dermatology clinic with a 0.6-cm
      eroded, erythematous, scaly plaque on the left side of his neck. On shave biopsy,
      the lesion was composed of intra-epidermal and invasive dermal cells
      characterized by a signet-ring appearance. One area suggestive of typical
      squamous cell carcinoma prompted the inclusion of that entity in the differential
      diagnosis. Mucicarmine stains were negative, while the extra-vacuolar cytoplasm
      focally reacted with periodic acid-Schiff staining, the positive reaction for
      which was abolished by diastase, consistent with glycogen. Malignant cells
      expressed keratins by reacting to antibodies, Mak6, AE1/AE3, Ker 903, and CAM5.2.
      Additionally, weak reactivity occurred with antibodies to CEA and EMA. Tumor
      cells did not express S-100, HM-B45, Leu M1, or actin. By ultrastructural
      examination, the large vacuoles corresponded to markedly dilated endoplasmic
      reticulum. A diagnosis of signet-ring squamous cell carcinoma, a rare form of
      cutaneous squamous cell carcinoma which has been described in only one case
      report in the last 10 years, was made. Immunohistochemical staining provided
      information useful in differentiating this lesion from other clear cell and
      signet-ring cell tumors which involve the skin.

PMID- 9550319
TI  - Does eccrine hidrocystoma exist?

PMID- 9550320
TI  - Cutaneous infiltrates of myelogenous leukemia in association with pre-existing
      skin diseases.

PMID- 9550321
TI  - Intracellular signal transduction mediated by ligation of MHC class I molecules.
AB  - A great deal of knowledge has accumulated regarding signal transduction after
      ligation of MHC class I (MHC-I) molecules. In recent years focus has been given
      to delineation of the intracellular signal pathways activated after MHC-I
      ligation. Activation of tyrosine kinases leading to a rise in the intracellular
      free calcium concentration ([Ca2+]i) is the major initial event occurring after
      MHC-I ligation of T cells. Curiously, the MHC-I-induced signaling is not
      dependent upon the cytoplasmic tail of the MHC-I molecule, suggesting that the
      MHC-I molecule induces intracellular signaling through association with other
      membrane-embedded molecules. More distal signaling events after MHC-I ligation
      includes activation of the Jak/Stat pathway leading to Stat-3 activation, and
      activation of the PI3-kinase leading to JNK activation and apoptosis. This review
      will sum up what is currently known about signaling induced by ligation of MHC-I.

PMID- 9550322
TI  - Genomic structure of PIR-B, the inhibitory member of the paired immunoglobulin
      like receptor genes in mice.
AB  - The genes encoding the murine paired immunoglobulin-like receptors PIR-A and PIR
      B are members of a novel gene family which encode cell-surface receptors bearing
      immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and their non
      inhibitory/activatory counterparts. PIR-A and PIR-B have highly homologous
      extracellular domains but distinct transmembrane and cytoplasmic regions. A
      charged arginine in the transmembrane region of PIR-A suggests its potential
      association with other transmembrane proteins to form a signal transducing unit.
      PIR-B, in contrast, has an uncharged transmembrane region and several ITIMs in
      its cytoplasmic tail. These characteristics suggest that PIR-A and PIR-B which
      are coordinately expressed by B cells and myeloid cells, serve counter-regulatory
      roles in humoral and inflammatory responses. In the present study we have
      determined the genomic structure of the single copy PIR-B gene. The gene consists
      of 15 exons and spans approximately 8 kilobases. The first exon contains the 5'
      untranslated region, the ATG translation start site, and approximately half of
      the leader peptide sequence. The remainder of the leader peptide sequence is
      encoded by exon 2. Exons 3-8 encode the six extracellular immunoglobulin-like
      domains and exons 9 and 10 code for the extracellular membrane proximal and
      transmembrane regions. The final five exons (exons 11-15) encode for the ITIM
      bearing cytoplasmic tail and the 3' untranslated region. The intron/exon
      boundaries of PIR-B obey the GT-AG rule and are in phase I, with the notable
      exception of the three boundaries determined for ITIM-containing exons. A
      microsatellite composed of the trinucleotide repeat AAG in the intron between
      exons 9 and 10 provides a useful marker for studying population genetics.

PMID- 9550323
TI  - Heterogeneity of CD44 expression among human B-cell subpopulations.
AB  - CD44 is a widely distributed cell surface glycoprotein that participates in a
      number of cellular adhesion and signal transduction processes. Germinal center B
      cells express very low levels of CD44, whereas their precursors and
      differentiation products express much higher levels. In immunofluorescence
      studies comparing 20 antibodies classified as being against the hematopoietic
      isoform of CD44, one antibody, A1G3, was unreactive with germinal center B cells,
      whereas the other antibodies showed low intensity but definite reactivity.
      Western blotting and sequential immunoprecipitation studies of lysates from
      density-separated lymphocyte fractions showed two bands that were differentially
      expressed and reacted differently with A1G3 compared with the other CD44
      antibodies. These results suggest that germinal center B cells and non-germinal
      center B cells express different forms of CD44. Of 21 malignant B-cell
      populations examined, 5 showed reactivity with a "standard" CD44 reagent and
      significantly reduced reactivity with A1G3, while one sample showed the opposite
      pattern and the remainder were positive for both reagents. Of 10 cell lines
      studied, 5 were differentially stained by A1G3 and a standard CD44 antibody. PCR
      amplification of reverse transcribed mRNA from sorted human tonsil B-cell
      subpopulations and Southern blotting showed that B cells express a number of
      splice isoforms of CD44. These results demonstrate that B cells express multiple
      forms of CD44; both splice insert isoforms and variants distinguished by A1G3;
      the form of CD44 expressed depends on B-cell differentiation state.

PMID- 9550324
TI  - Failure of TGF beta1 and IL-12 to regulate human FasL and mTNF alloreactive
      cytotoxic T-cell pathways.
AB  - The effect of TGFbeta1 and IL-12 on calcium-independent cytotoxic pathways was
      investigated. We have previously demonstrated that the regulatory effect of
      TGFbeta1 and IL-12 on human alloreative CTL activity was associated with
      regulation of perforin and granzyme B gene expression. To determine the effect of
      both cytokines on the alternative cytotoxic pathway involving FasL and mTNF, we
      first investigated the expression of both molecules on human primary
      alloactivated T cells. Our results show that human allostimulated T lymphocytes
      express FasL. Cell lysis experiments demonstrate that the FasL cytotoxic pathway
      is involved in the killing of specific target cells mediated by human
      alloreactive CTL. In addition, allogeneic stimulation induced significant mTNF
      expression on both CD4+ and CD8+ responder T cells. Using TNF-sensitive target
      cells, we also demonstrate that the mTNF-mediated cytotoxic pathway is involved
      in the cytotoxic activity of human primary allostimulated T lymphocytes. Neither
      TGFbeta1 nor IL-12 had an effect on FasL or mTNF expression. Furthermore,
      addition of TGFbeta1 or IL-12 at the initiation of the MLR had no significant
      effect on Fas- and mTNF-mediated cytotoxicity. Taken together, our results
      provide a novel insight into the differences between regulation by cytokines of
      perforin-dependent and -independent cytotoxic mechanisms. Unlike their role in
      the perforin/granzyme B pathway, TGFbeta1 and IL-12 do not appear to mediate any
      regulatory effect on FasL and mTNF cytotoxic pathways used by human alloreactive
      primary CTL.

PMID- 9550325
TI  - Phenotypical and functional characterization of Herpesvirus saimiri-immortalized
      human major histocompatibility complex class II-deficient T lymphocytes.
AB  - CD8+ T lymphocytes from two unrelated cases of MHC class II deficiency were
      immortalized in vitro using Herpesvirus saimiri. In both cases, a lack of
      expression of surface MHC class II molecules was ascertained, whereas variable
      defects were shown for MHC class I, CD74 (invariant chain) and LAG-3 (an MHC
      class II ligand). The functional analysis of both H. saimiri-immortalized T-cell
      lines revealed the existence of a proliferation impairment in response to anti
      CD3 but not to other surface or transmembrane stimuli. Further characterization
      of this functional defect indicated that it was not associated with impaired
      early activation events (like calcium flux) but, rather, with certain late
      events, like the induction of IL-2. H. saimiri-immortalized T cells may be
      valuable in studying the biological role of MHC class II molecules in activated
      human T cells.

PMID- 9550326
TI  - Human monoclonal antibody with T-cell-like specificity recognizes MHC class I
      self-peptide presented by HLA-DR1 on activated cells.
AB  - Alloreactive T cells recognize peptides presented in the binding groove of major
      histocompatibility complex molecules (MHCs), whereas B cells mainly recognize the
      MHCs independent of bound peptides. Here, we demonstrate that the human B-cell
      repertoire comprises B cells which can be stimulated during pregnancy to produce
      antibodies reacting with MHCs in a way similar to T cells. The human monoclonal
      antibody UL-5A1 recognizes DR1(DRA/DRB1*0101) molecules on lymphoblastoid cell
      lines only if they co-express HLA-A2 or if they have been loaded with HLA-A2
      derived peptides. The effect of the HLA-A2 peptide 105-117 on UL-5A1 reactivity
      was specific, time and dose-dependent. Reactivity increased when naturally
      processed peptides were removed from DR1 molecules before the HLA-A2 peptide 105
      117 was loaded. UL-5A1 reacted specifically with cells that had been activated.
      The results imply a role of activation of cells in peptide processing and/or
      loading.

PMID- 9550328
TI  - HLA-DR and -DQ alleles in Italian patients with melanoma.
AB  - Controversial data have been reported about HLA alleles and susceptibility to
      melanoma. Our investigation was undertaken to analyze the relationship between
      HLA alleles distribution in patients with melanoma and susceptibility to the
      tumor, in order to study the possible correlation between HLA class II DQA1, DQB1
      and DRB1 genes involved in immune recognition, and melanoma, usually considered a
      highly immunogenic tumor. We therefore typed by means of PCR-SSP (sequence
      specific primers) 53 Italian patients and 53 healthy random controls coming from
      the same geographic area. We observed a decrease of all haplotypes bearing
      DQB1*0301, DQB1*0302 and DQB1*0303 alleles but not of haplotype
      DRB1*11;DQA1*0501;DQB1*0301. Our results seem to support the hypothesis of a
      protective role of some DQ3-bearing haplotypic combinations in melanoma.

PMID- 9550327
TI  - HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic
      hemochromatosis.
AB  - Genetic hemochromatosis (GH) is closely associated with genes of the major
      histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for
      GH, with structural similarities to MHC class I genes, designated HLA-H and
      presently named HFE, has been cloned. The HFE gene is localized telomeric to the
      MHC and several reports have indicated that the HFE gene is mutated in GH
      patients. In the present study we have analyzed the relationship of HFE gene
      variants and disease manifestation in GH patients and family members. Fifty-seven
      patients with GH, 73 family members and 153 healthy blood donors were studied for
      the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr=
      C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR
      amplification of genomic DNA samples and restriction enzyme digestion using
      RsaI/SnaBI for C282Y and BclI/MboI for H63D. Ferritin, transferrin serum levels
      and total iron-binding capacity were determined prior to therapeutic
      intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared
      with 8 (5.2%) of controls (OR=169, P<0.0001). Fifty-one (90%) patients were Tyr
      282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of
      the patients compared with 34 (22%) of controls (OR=0.39, P=NS) with none of the
      patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin
      levels, transferrin saturation, liver iron and liver iron index were elevated
      significantly compared to Tyr-282-negative patients, whereas no difference was
      observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients.

PMID- 9550330
TI  - Major histocompatibility complex class II alleles in an Uygur population in the
      Silk Route of Northwest China.
AB  - HLA class II (DRB1, DQA1, DQB1 and DPB1) genotyping was performed in 57 unrelated
      Uygur individuals inhabiting the northwestern China area by the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among 98
      DRB1 alleles tested, 23 alleles were detected, and DRB1*0701 (16.7%) and
      DRB1*0301 (14.0%) were the most and the second most common alleles, respectively.
      In 8 DQA1 alleles detected, DQA1*05 (26.3%), DQA1*03 (21.9%) and DQA1*0201
      (21.1%) were very frequent. Of 21 DQB1 alleles tested, 13 were observed. Among
      them, DQB1*02 was highly predominant with the gene frequency of 32.5%. Of 46 DPB1
      alleles tested, 15 were detected, among which DPB1*0401 (31.6%) was the most
      frequent. Two haplotypes predominate clearly; DRB1*0701-DQA1*0201-DQB1*02 (15.5%)
      and DRB1*0301-DQA1*05-DQB1*02 (12.6%). The dendrogram constructed by the
      neighbour-joining (NJ) method based on the allele frequencies of the DRB1, DQA1,
      DQB1 and DPB1 genes of 13 representative populations all over the world suggested
      that Uygur belonged to the Asian group and lay at the closest genetic distance to
      a Kazak population inhabiting the same area.

PMID- 9550329
TI  - Association between autoantibody markers and subtypes of DR4 and DR4-DQ in
      Swedish children with insulin-dependent diabetes reveals closer association of
      tyrosine pyrophosphatase autoimmunity with DR4 than DQ8.
AB  - HLA DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) are positively and
      DQA1*0102-DQB1*0602 (DQ6) negatively associated with IDDM. In DQA1*0301-DQB1*0302
      (DQ8)-positive patients, susceptibility is also mediated by DRB1*0401. The aim of
      the study was to determine the association between HLA-DR4 and DQ and the
      presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425
      Swedish children with IDDM and 367 controls in the age group of 0-15 years. We
      found that ICA512 autoantibodies were associated primarily with DRB1*0401 and not
      with DQA1*0301-DQB1*0302 (DQ8). No such hierarchy could be demonstrated for
      insulin autoantibodies, which were associated with both DQA1*0301-DQB1*0302 (DQ8)
      and DRB1*0401. GAD65 autoantibodies, known to be closely associated with
      DQA1*0501-DQB1*0201 (DQ2)-DRB1*0301 haplotype, also showed no preferential
      association with DQA1*0301-DQB1*0302 (DQ8) versus DRB1*04. These results suggest
      that the immune response to different beta-cell autoantigens may be mediated via
      HLA class II molecules from different loci. Design of the antigen-specific immuno
      intervention trials should take into account these HLA-DR and DQ subtype
      associations.

PMID- 9550332
TI  - Soluble HLA class I and class II antigens in patients with multiple sclerosis.
AB  - Soluble HLA class I (sHLA-I) and soluble HLA class II (sHLA-II) antigen levels
      during different stages of disease were investigated in paired serum and
      cerebrospinal fluid (CSF) samples from 37 patients with multiple sclerosis (MS)
      using ELISA and Western blot analysis. Soluble HLA-II antigens in the serum of
      untreated patients with the relapsing-remitting type of MS (RRMS) were found to
      be significantly elevated in acute relapse as compared to values obtained from
      patients under steroid treatment, in remission or healthy controls. No
      significant differences in circulating sHLA-I levels could be detected. In
      contrast, a trend towards increased intrathecal production of sHLA-I molecules in
      the CSF was observed in untreated RRMS patients in acute relapse, whereas the
      levels of soluble HLA-II antigens in the CSF were below the detection limit of
      the ELISA method. Our observations underline the presence of systemic immune
      activation in MS patients, as reflected in elevated serum sHLA-II antigen levels,
      and reveal a dichotomy between sHLA class I and II antigen production in the
      peripheral blood versus CSF in acute MS. Serial measurements of sHLA-II antigen
      levels might represent a non-invasive method to assess disease activity in MS
      patients.

PMID- 9550331
TI  - Allele-specific HLA-B*15 typing by PCR-SSP and its application to four distinct
      ethnic populations.
AB  - We present a set of primer mixes for the allele-specific typing of the HLA-B*15
      group by PCR-SSP. The set comprises 46 primer mixes which are designed to
      unequivocally resolve all but two of the 666 possible combinations of the B*15
      alleles, B*1501-37 (B*1536 sequence unavailable). A core subset of 34 of the 46
      mixes can be used alone to give a high resolution B*15 typing set. This allows
      for the identification of each B*15 allele when present as the only B*15 allele
      and the majority of the possible B*15 homozygotic combinations. The method was
      validated using reference DNA samples and the B*15 allele frequency in 4 distinct
      ethnic populations was investigated. The results show that these populations
      contain predominantly mutually exclusive sets of B*15 alleles.

PMID- 9550333
TI  - Extended HLA haplotypes in Japanese homozygous typing cells.
AB  - We have defined extended HLA haplotypes including the HLA class II genes, the non
      HLA genes such as TAP1, TAP2 and LMP2, and the (CTG)n microsatellite repeats
      within the NOTCH4 gene between DRA and 21OH in 33 Japanese HLA homozygous typing
      cells (HTC). These conserved haplotypes characterized by unique linkage might be
      maintained as a result of functional co-operation among them in the antigen
      presentation pathway. These HTCs can be served as an original and ethnic-specific
      standard panel, providing useful genetic markers in haplotypic diversity, disease
      association, and anthropology studies.

PMID- 9550334
TI  - MICA exon 5 microsatellite typing by DNA heteroduplex analysis: a new
      polymorphism in the transmembrane region.
AB  - MICA (MHC class I chain-related gene A) is localized 47 kb upstream from HLA-B on
      the short arm of chromosome 6. It has been postulated that MICA protein folds
      similarly to the class I chain and may have the capacity to bind short ligands.
      Short tandem repeats (STR) within the transmembrane (TM) region of this gene have
      been described and five alleles consisting of 4 to 9 GCT codons, each encoding an
      alanine residue have been defined. We have applied DNA heteroduplex analysis to
      type MICA trinucleotide repeats in order to develop a simple and reliable method
      for their identification. This approach allowed the characterization of all MICA
      alleles. Moreover, a new polymorphism within the TM region was identified.

PMID- 9550335
TI  - HLA-A*02172* adds to the heterogeneity of HLA-A*02 alleles.

PMID- 9550336
TI  - Nomenclature for factors of the HLA system, update September/October 1997.

PMID- 9550337
TI  - Nomenclature for factors of the HLA system, update November/December 1997.

PMID- 9550338
TI  - Parameters and symbols for use in nuclear magnetic resonance (IUPAC
      recommendations 1997).
AB  - NMR is now frequently the technique of choice for the determination of chemical
      structure in solution. Its uses also span structure in solids and mobility at the
      molecular level in all phases. The research literature in the subject is vast and
      ever-increasing. Unfortunately, many articles do not contain sufficient
      information for experiments to be repeated elsewhere, and there are many
      variations in the usage of symbols for the same physical quantity. It is the aim
      of the present recommendations to provide simple check-lists that will enable
      such problems to be minimised in a way that is consistent with general IUPAC
      formulation. The area of medical NMR and imaging is not specifically addressed in
      these recommendations, which are principally aimed at the mainstream use of NMR
      by chemists (of all sub-disciplines) and by many physicists, biologists,
      materials scientists and geologists etc. working with NMR. The document presents
      recommended notation for use in journal publications involving a significant
      contribution of nuclear magnetic resonance (NMR) spectroscopy. The
      recommendations are in two parts: (1) Experimental parameters which should be
      listed so that the work in question can be repeated elsewhere. (2) A list of
      symbols (using Roman or Greek characters) to be used for quantities relevant to
      NMR.

PMID- 9550339
TI  - Molecular dynamics in solid L-adrenaline by proton NMR.
AB  - Proton NMR measurements of the spectrum, second moment, spin-lattice relaxation
      time T1 and dipolar relaxation time T1D were carried out on polycrystalline L
      adrenaline at 14 and 25 MHz between 55 and 400 K. Between 70 K and 250 K
      relaxation is dominated by C3 reorientation of the single methyl group in each
      molecule, characterized by an activation energy 8.3+/-0.3 kJ/mole. Below 70 K
      tunnelling assisted relaxation is significant, characterized by an excitation
      energy of 1.9+/-0.2 kJ/mole. Above 250 K an additional molecular motion becomes
      significant, with activation energy above 28 kJ/mole, attributed to
      conformational motion of the methylene group in the ethylamine side chain.

PMID- 9550340
TI  - 13C CP MAS NMR study of 6-O-(beta-D-glucopyranosyl)- and 6-O-(beta-D
      mannopyranosyl)-d-alpha-tocopherols.
AB  - 13C NMR CP MAS data for three glycosyl alpha-tocopherol derivatives are reported.
      The values of delta = delta(solution) - delta(solid state) provided information
      about rigid and conformationally flexible fragments of alpha-tocopherol molecule
      and the sugar moieties.

PMID- 9550341
TI  - Five quantum coherence of I=5/2 nuclei: 27Al in polycrystalline AlCl3.
AB  - Optimal conditions were calculated for the excitation and detection of the five
      quantum coherence of quadrupolar nuclei with I = 5/2 in powder samples, observed
      by the two-pulse sequence (theta1)x - tau1 - (theta2)alpha - tau2, where alpha is
      the phase cycling angle. We varied the pulse lengths and the relative values of
      the nutation frequency omega1 = gammaB1 and the quadrupolar frequency omegaQ.
      Also, the effect of the resonance offset was studied under optimal conditions.
      Besides, the conditions for obtaining the maximal echo amplitude after the two
      pulse sequence with alpha = y were found. Theoretical results were compared with
      experiments on 27Al nuclei in polycrystalline AlCl3.

PMID- 9550342
TI  - Time symmetry: an application to shaped pulse excitation of spin-1 systems.
AB  - The role of time symmetry in the design of amplitude-modulated (shaped) pulses
      for spin-1 excitation is examined. The quaternion calculus is used to calculate
      the quaternion elements (Euler-Rodrigues parameters) of each shaped pulse. In
      this manner, it is shown how the simplicity and compactness of the Euler
      Rodrigues parametrization can be used to significantly expedite a computer search
      for optimal time-symmetric shaped pulses. Theoretical and experimental tests of a
      new class of symmetric quadrupole-shaped (SQUASH) pulses identified by this
      procedure show a significant improvement in both excitation bandwidth and
      efficiency in comparison to the time-asymmetric QUASH shaped pulse previously
      identified.

PMID- 9550343
TI  - 1H/27Al TRAPDOR NMR studies on aluminum species in dealuminated zeolites.
AB  - Aluminum species in several dealuminated zeolites (ultrastable HY, HZSM-5 and
      mordenite) were investigated in detail by means of the newly introduced 1H/27Al
      TRAPDOR method in combination with 27Al MAS NMR, and the quadrupole coupling
      constants (Q[CC]s) for aluminum atoms associated with these species were
      obtained. A signal at ca. 6.8 ppm, due to water molecules adsorbed on Lewis acid
      sites, was observed in the 1H MAS spectra for all the three zeolites. The TRAPDOR
      NMR provides direct evidence that there is a strong interaction between the
      adsorbed water molecules and the aluminum atoms of the Lewis-acid sites. The
      Q(CC) values for this aluminum species of 8.3, 6.7 and 11.3 MHz were determined
      from the TRAPDOR profiles for the ultrastable HY, HZSM-5 and mordenite zeolites,
      respectively. The Q(CC)s calculated from the TRAPDOR curves are usually larger
      than 10 MHz for both Bronsted-acid sites (SiOHAI) and non-framework aluminum
      species in the three zeolites. Three narrow peaks at 54, 30 and 0 ppm are
      separately superimposed on a broad hump in the 27Al MAS spectra of the three
      dehydrated zeolites, while the latter is associated with the 'NMR invisible' Al.
      The NMR experimental results suggest that the three kinds of aluminum species
      (non-framework aluminum species, Bronsted- and Lewis-acid sites) are all
      responsible for the resonance of the broad hump in dehydrated zeolites, which
      makes it difficult to explain the 27Al MAS spectra. Fortunately, the TRAPDOR NMR
      provides a direct method for individually studying different aluminum species
      with large Q(CC)s via their dipolar coupling to nearby proton nuclei.

PMID- 9550344
TI  - Methyl tunnelling, reorientation and NMR relaxation in solid acetates.
AB  - Rotational excitations of methyl groups in six solid acetates have been
      investigated by 1H nuclear magnetic resonance (NMR) relaxation time measurements
      at 15 MHz and 30 MHz and at temperatures between 10 K and the melting point.
      Hindering barriers between 1.6 kJ/mol and 3.7 kJ/mol have been found that could
      be correlated to the tunnelling frequencies observed by inelastic neutron
      scattering. A consistent description of the relaxation rate dependences from the
      classical regime at high temperatures to the quantum-mechanical regime at low
      temperatures is possible by Haupt's equation. The rotational potentials are
      mainly determined by inter-molecular interaction with an important influence of
      water of crystallization, if present.

PMID- 9550345
TI  - 23Na NMR studies of Na-DNA in the solid state.
AB  - 23Na MAS, CP/MAS and quadrupole nutation NMR spectra and the 23Na spin-lattice
      relaxation times in Na-DNA with and without competing species (Mg2+, ethidium
      bromide and [Ru(phen)3]2+) reveal the presence of two sodium sites with different
      NMR parameters. While in the presence of Mg2+, sodium resides far from the
      surface of the DNA molecule, ethidium bromide and [Ru(phen)3]2+ displace sodium
      closer towards the surface.

PMID- 9550346
TI  - Conventions for tensor quantities used in NMR, NQR and ESR.

PMID- 9550347
TI  - Effect of topical cyclosporin A on Thygeson's superficial punctate keratitis.
AB  - Thygeson's superficial punctate keratitis (Thygeson's SPK) is a distinct clinical
      entity, characterized by round conglomerates of discrete, granular, white-gray,
      fine intraepithelial dots without conjunctival involvement. The only effective
      treatment with regard to relieving symptoms and diminishing lesions has been
      topical corticosteroids, but their prolonged use can be associated with severe
      side-effects. The purpose of this study is to present the long-term results of
      the use of 2% topical cyclosporin A in olive oil in Thygeson's SPK. Eight
      patients diagnosed as having Thygeson's SPK were included. All the patients were
      treated with 2% cyclosporin dissolved in olive oil four times a day for three
      months, and two times a day for one month before withdrawing therapy. The follow
      up period ranged from twelve to twenty-five months. The number of corneal lesions
      varied between 5 and 15 before treatment. After cyclosporin treatment, no corneal
      lesion was observed and the cornea remained clear after the follow-up period. In
      conclusion, 2% cyclosporin in olive oil is a safe alternative to corticosteroids
      in the treatment of Thygeson's SPK, and resulted in satisfactory control of the
      condition.

PMID- 9550348
TI  - Measuring contrast sensitivity in aretinopathic patients with Insulin Dependent
      Diabetes Mellitus.
AB  - Contrast sensitivity measurements were obtained from 66 patients with Insulin
      Dependent Diabetes Mellitus (IDDM) and no visible diabetic retinopathy (Group A,
      n = 30 prepubescent and pubescent subjects; Group B, n = 36 postpubescent
      subjects). Contrast thresholds were determined for stationary and 6.87 Hz phase
      alternating gratings at eight spatial frequencies from 0.18 to 15.7 c/deg. Data
      from each group of diabetic patients was compared with data from puberty-matched
      normal subjects. Mean value of the last four determinations of glycohemoglobin
      Alc (HbAlc) was used as a index of glycemic control. We found that patients with
      IDDM and no retinopathy had normal contrast sensitivity and that contrast
      thresholds were not significantly related to sexual maturity, duration of
      diabetes and glycemic control.

PMID- 9550349
TI  - Comparative experimental study of 10% and 15% medical gelatin in the anterior
      chamber and in the posterior eye segment as a viscosubstance in the viscosurgery.
AB  - This article discusses the possibility of application of 15% medical gelatin
      solution compared to 10% medical gelatin solution in the anterior chamber and in
      the posterior eye segment as a viscosubstance in the viscosurgery. The
      experimental investigations were performed on 24 Chinchilla rabbits, divided in
      two groups consisting of 12 each. 0.5 ml of 10% and 15% of medical gelatin were
      injected in the anterior chamber and 2 ml of 10% and 15% medical gelatin were
      injected in the vitreous body of the tested eyes. 2% methyl cellulose and 0.89%
      Sodium Chloride were injected in the vitreous body of the control eyes. Clinical,
      biomicroscopical, ophthalmoscopical, tonometrical, histological and electron
      microscopical examinations were performed. It was established that when the eyes
      were injected with 10% and 15% medical gelatin, as well as with 0.89% Sodium
      Chloride, the intraocular pressure was not increased but when the eyes were
      injected with methyl cellulose the intraocular pressure was increased. We also
      found that 15% of medical gelatin has longer effect than 10% medical gelatin.
      Toxoallergic and inflammatory changes were not observed in the eyes injected with
      10% and 15% medical gelatin. In the same eyes, histologically and by electron
      microscopy, were not found any changes in the layers of the cornea and retina.
      These substances could be used as viscosubstances and as instruments in surgical
      interventions of the anterior eye segment and in the posterior eye segment
      (vitrectomy).

PMID- 9550350
TI  - Malondialdehyde serum concentration in type 1 diabetic with and without
      retinopathy.
AB  - Lipid peroxides are thought to be formed by free radicals and have been
      implicated in the pathogenesis of diabetes complications. A convenient and
      sensitive method for estimation of lipid peroxide concentration is the
      quantitative estimation of their metabolic end-product malondialdehyde (MDA)
      expressed in mmol/L using the thiobarbituric acid test (TBA-test). We have
      measured the serum concentrations of MDA in 60 well controlled type I diabetic
      patients (28 without retinopathy and 32 with retinopathy) and 13 age-matched
      healthy subjects. Patients with retinopathy showed significantly increased MDA
      level (2.65+/-1.00) compared to diabetics without retinopathy (1.80+/-0.81) and
      healthy controls (1.47+/-0.45). The serum levels of MDA correlated best with
      glycosylated haemoglobin (r=0.28), serum triglyceride concentration (r=0.29) and
      serum cholesterol concentration. (r=0.47). Increased lipid peroxides suggesting
      increased free radical activity is associated with retinopathy and this may have
      pathogenetic implications.

PMID- 9550351
TI  - Effects of allopurinol on free-radical-induced reduction of the proliferation of
      retinal pigment epithelial cells.
AB  - PURPOSE: To investigate the effects of allopurinol on free-radical-induced
      reduction of growth of retinal pigment epithelial (RPE) cells. METHODS: Bovine
      RPE cells were seeded at a density of 1 x 10(5) cells/Petri dish (60 x 15 mm)
      containing 4 ml MEM-Earle plus 15% FCS plus antibiotics. Twenty-four hours after
      seeding, cultures were exposed to a free radical generating system
      hypoxanthine(HX)/xanthine oxidase (XO) (HX: 0.1 micromol/l; XO: 700 microU/ml)
      for 10 or 60 min. Thereafter, the cells were washed. After washing the cells,
      allopurinol was added at 500 or 1000 micromol. To evaluate the effect of the
      radical generating system one group was not washed after treatment ('no wash').
      The cultures were divided into eight groups: (1) no treatment (control); (2)
      HX/XO, no wash; (3,4) HX/XO, washed after 10 or 60 min; (5,6) HX/XO, washed after
      10 or 60 min, application of 500 micromol of allopurinol; (7,8) HX/XO, washed
      after 10 or 60 min, application of 1000 micromol of allopurinol. Cell counts were
      carried out 96 h post-seeding. The values are expressed as means +/- SE. RESULTS:
      After 72 h (HX/XO, no wash), the radical generating system resulted in a
      significant decrease in cell growth as compared to controls. When being
      eliminated after 10 or 60 min, the radical generating system also led to
      significant decrease in the values as compared to controls. Allopurinol
      treatment: All therapy (scavenger) groups (4,5) were significantly different from
      the respective control group; following exposition to the radical generating
      system for 60 min, allopurinol showed significantly higher values when given at
      1000 micromol as compared to 500 micromol. CONCLUSIONS: The results demonstrate
      that allopurinol, when given at a scavenger dose (500-1000 micromol), can prevent
      free-radical-induced cell damage and stop chain reactions. Thus, the possible
      beneficial value of allopurinol on diseases with involvement of oxidative tissue
      damage, such as age-related macular degeneration, should be investigated further.

PMID- 9550352
TI  - Clinical experience with cyanoacrylate tissue adhesive.
AB  - In this paper 385 cases treated with cyanoacrylate tissue adhesive during the
      years 1980-1995 are studied. The indications, outcomes and complications of
      cyanoacrylate adhesive are investigated and the results are analysed. It is
      encouraging that except for three cases of ocular hypotony and two cases of
      microbial infection no other complications occurred. Even in desperate cases with
      corneal perforation greater than 3 mm and ocular infection, enucleation was
      avoided. The early use of a bandage contact lens, inserted just after the glue
      application and the coverage with topical antibiotics switched every 15 days
      until the removal of the glue, may explain the small incidence of infection. Our
      experience from the use of cyanoacrylate tissue adhesive in cases with corneal
      perforation greater than 3 mm is very encouraging. In these cases a running 10.0
      nylon suture was used to create a reticulum over the space of the corneal
      perforation upon which the glue was applied. The use of cyanoacrylate tissue
      adhesive offers to the clinician a safe technique for healing corneal wounds that
      avoids tectonic penetrating keratoplasty with its associated complications.

PMID- 9550353
TI  - Cytidin-5'-diphosphocholine enhances the effect of part-time occlusion in
      amblyopia.
AB  - Cytidin-5'-diphosphocholine (CDP-choline) has been shown to improve visual acuity
      (VA), Contrast Sensitivity and Visual Evoked Responses at least temporarily, in
      amblyopic patients beyond the plastic period of the visual system. In this paper
      results are presented of a study conducted on forty-five patients with amblyopia
      in one eye, aged 5-9 years and followed for one year. Of them, 15 (Group A) were
      treated with CDP-choline (500 mg daily for 10 days every six months); 15 (Group
      B) were treated with CDP-choline plus one hour of occlusion daily; 15 (Group C)
      were treated with one hour of occlusion daily. The final VA values were
      statistically different from the initial ones, for all three groups. Eleven of
      the Group A patients showed an improvement in VA after the first treatment; a
      gradual deterioration took place in 6 patients at the end of the fourth month; VA
      further improved in 9 patients after the second treatment. At the end of the
      year, VA was higher than at the beginning in 12 of the 15 patients. Group B had
      an improvement of VA in 13 patients, starting 10 days from the beginning of
      treatment. This improvement continued throughout the observation period. Group C
      had an improvement after one month, which continued for 8 months, without
      deteriorating. In conclusion CDP-choline enhances the effect of part-time
      occlusion. CDP-choline could be employed also in younger patients. Longer
      observation periods are still needed and better means of administration have to
      be found.

PMID- 9550354
TI  - A new electromechanical method for measuring intraocular pressure.
AB  - A new electromechanical method to measure intraocular pressure is presented. A
      light probe was made to collide with an eye (cornea or sclera) and to bounce
      back. The impact was registered by an acceleration sensor or the duration of
      contact with the eye was measured using the phenomenon of the electrical
      conductivity of biological objects. Laboratory experiments were carried out using
      pig eyes pressurized with water leveled to different heights. Preliminary
      clinical trials were carried out comparing the values obtained with those of the
      Goldmann applanation tonometer. The time of contact and the deceleration time
      decreases and the deceleration maximum increases in proportion with IOP. A new
      kind of tonometer can be constructed based on this principle. Measurement can be
      performed to cornea or sclera without an anesthetic drop. Further study is
      required to evaluate the accuracy and usefulness of this method.

PMID- 9550355
TI  - Lumping and splitting: molecular biology in the genetics clinic.

PMID- 9550356
TI  - Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients
      and clinical characterization of spinocerebellar ataxia type 6.
AB  - Using a molecular diagnostic approach, we investigated 101 kindreds with
      autosomal dominant cerebellar ataxias (ADCAs) from the central Honshu island of
      Japan, including spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia
      type 2 (SCA2), Machado-Joseph disease (MJD), dentatorubral and pallidoluysian
      atrophy (DRPLA) and spinocerebellar ataxia type 6 (SCA6). In our unselected
      series, MJD was the most common type of ADCA, accounting for 33.7% followed by
      DRPLA (19.8%), SCA2 (5.9%) and SCA6 (5.9%). No SCA1 mutations were identified. We
      analysed the clinical features of six molecular confirmed SCA6 kindreds: in each
      family, there was an expanded allele in the alpha1A-voltage dependent calcium
      channel comprising between 23 and 25 CAG repeats. The mean age at onset of
      symptoms was 43+/-13 years. The clinical features consisted predominantly of
      cerebellar ataxia, dysarthria and horizontal nystagmus, which was generally
      consistent with ADCA type 3. However several new clinical features were found in
      some patients: dramatic anticipation, rapid disease progression, severe ataxia
      associated with action tremor or action myoclonus, and very early onset, which
      are not described as the classical features of ADCA type 3.

PMID- 9550357
TI  - Genotype-phenotype correlation in myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is caused by a mutation in the length of a trinucleotide
      (CTG) repeat in the 3' untranslated region of the myotonin protein kinase gene
      located on chromosome 19q13.3. The normal gene has between 5 and 36 CTG
      trinucleotide repeats, whereas minimally affected individuals have 50 copies and
      severely affected DM-patients have several thousands of such repeats. Since no
      information on a genotype phenotype correlation in Austrian DM-patients is
      available, we examined a small group of these patients for the unstable
      trinucleotide repeat. Molecular analysis was used to clarify equivocal clinical
      diagnoses and confirm clinical findings. We studied eight DM-families, a total of
      57 individuals, of whom 18 were diagnosed with a trinucleotide repeat expansion.
      Twenty-six unrelated individuals served as a control. Clinical assessment was
      based on the muscular disability rating scale (MDRS) and a sum of symptoms score
      (SSS). There was a significant correlation between the clinical scores (MDRS:
      Spearman r = 0.51; p = 0.029: SSS: Spearman r = 0.538; p = 0.0259) used and the
      size of the amplification of the trinucleotide repeat. The largest expansion
      found in our group of patients was 6 kb. Furthermore, we observed both expansion
      and contraction of the enlarged fragment during transmission from one generation
      to the next.

PMID- 9550358
TI  - The Asn9 variant of lipoprotein lipase is associated with the -93G promoter
      mutation and an increased risk of coronary artery disease. The Regress Study
      Group.
AB  - Two mutations in the lipoprotein lipase (LPL) gene, a T to G transition at
      position -93 of the proximal promoter region and an Asp9Asn substitution in exon
      2, were examined in 762 Dutch males with angiographically-diagnosed coronary
      artery disease (CAD) and 296 healthy normolipidemic Dutch males. The two
      mutations exhibited strong linkage disequilibrium (D' = 0.975). A significantly
      higher proportion of cases (4.86%) than controls (1.37%) carried the -93G/Asn9
      allele (p = 0.008). In the combined sample of cases and controls, adjusted mean
      plasma total cholesterol (TC) levels were significantly higher in -93G/Asn9
      carriers (6.20+/-0.13 mmol/l) than in non-carriers (5.93+/-0.03 mmol/l; p =
      0.048), while mean high-density lipoprotein cholesterol (HDL-C) levels were lower
      in carriers (0.88+/-0.03 mmol/l) than in non-carriers (0.98+/-0.01 mmol/l; p =
      0.002). There was a trend towards higher triglyceride (TG) levels in carriers
      (1.96+/-0.14 mmol/l) compared with non-carriers (1.73+/-0.03 mmol/l) (p = 0.08).
      Additionally, carrier frequencies in tertiles of TC, HDL-C, TG, and LPL activity,
      suggested an association of the -93G/Asn9 variant with higher TC and TG levels,
      and with lower HDL-C and LPL activity levels. Logistic regression revealed a
      significant odds ratio (OR) for the combined -93G/Asn9 genotype in CAD cases
      relative to controls (OR: 5.36; 95% CI: 1.57-18.24), with age, body mass index
      (BMI), smoking, and plasma total- and HDL-cholesterol levels included in the
      model. In conclusion, we show that the LPL Asp9Asn mutation is in non-random
      association with a T G substitution at position -93 of the proximal promoter
      region and that the combined -93G/Asn9 genotype predisposes to decreased HDL-C
      levels and an increased risk of CAD.

PMID- 9550359
TI  - A clinical, cytogenetic and molecular study of ten probands with supernumerary
      inv dup (15) marker chromosomes.
AB  - Ten probands with moderate to severe developmental delay were found to have a
      supernumerary inv dup (15) chromosome. These patients and their families were
      studied by both cytogenetic and molecular methods. Cytogenetic polymorphisms
      associated with the 15p short arm suggested a maternal derivation for the marker
      chromosome in all informative cases. One marker was directly maternally
      inherited. Molecular analysis employing Southern blotting and polymerase chain
      reaction (PCR) of microsatellite repeats demonstrated the presence of extra
      alleles in the 15q11q13 region. All ten of the probands demonstrated an extra
      band at one or more locus without recourse to densitometry. All of the inv dup
      (15) markers were comparable in size to a G group chromosome but there were
      differences in the positions of the breakpoints in 15q. There was an inconsistent
      relationship between marker size, gene dosage and severity of phenotype.

PMID- 9550360
TI  - Complete identification of cystic fibrosis transmembrane conductance regulator
      mutations in the CF population of Saguenay Lac-Saint-Jean (Quebec, Canada).
AB  - Over the past few years, we have conducted a systematic study of 230 cystic
      fibrosis (CF) chromosomes in the Saguenay Lac-Saint-Jean (SLSJ) population which
      has a high CF incidence (1/936 live births). We identified 11 mutations
      accounting for 100% of the CF chromosomes found in patients born in SLSJ. Our
      results indicate that denaturing gradient gel electrophoresis (DGGE) is a
      powerful method of identifying CF mutations. They have also considerable
      implications for genetic counselling and molecular characterization of doubtful
      patients. They make carrier screening technically feasible in this population.

PMID- 9550361
TI  - The incidence of cystic fibrosis in Scotland calculated from heterozygote
      frequencies.
AB  - The incidence of cystic fibrosis (CF) has previously been calculated from
      epidemiological surveys and from neonatal screening. With the cloning of the CF
      gene it has become possible to derive incidence figures from heterozygote
      frequencies, provided that the distribution of mutant alleles among healthy
      carriers is the same as among affected people. We have estimated the allele
      frequencies for four CF mutations, AF508, G551D, G542X and R117H, in 14360
      unselected women undergoing antenatal heterozygote screening. The proportion of
      R117H, an allele of known mild effect, was much greater for heterozygotes than
      for homozygotes. The incidence of CF was therefore calculated from the
      heterozygote frequencies of AF508, G551D and G542X in a larger cohort of 27 161
      successively screened women. The point estimate for the incidence of CF in the
      Scottish population was 1 in 1984, with 95% confidence intervals of 1 in 1692 to
      1 in 2336.

PMID- 9550362
TI  - Severe cystic fibrosis associated with a deltaF508/R347H + D979A compound
      heterozygous genotype.
AB  - This report is concerned with twins with cystic fibrosis (CF). They are of mixed
      parentage: Japanese mother and German father. One case is presented with meconium
      ileus as a neonate. The other patient did relatively well until the age of 6
      years when she was first hospitalized and diagnosed with pulmonary aspergillosis.
      They have been receiving standard therapies for CF including digestive enzymes,
      vitamins and periodic antibiotic therapy in the US. At 19 years of age, they were
      tested for common mutations and one AF508 cystic fibrosis transmembrane
      conductance regulator (CFTR) allele was found. Further testing of their CFTR gene
      as well as those of their Japanese mother and grandmother revealed missense
      mutations in exon 7 (R347H) and exon 16 (D979A). Although the D979A mutant is
      very rare, this mutation combination seemed to be responsible for severe CF
      phenotypes.

PMID- 9550363
TI  - Association between asthma and an intragenic variant of CC16 on chromosome 11q13.
AB  - The beta subunit of high affinity immunoglobulin E (IgE) receptor
      (FcepsilonRIbeta) and the Clara cell derived inflammatory molecule, CC16 have
      been cited as candidate genes for atopic asthma on chromosome 11q13. A genetic
      association study was performed with an intragenic microsatellite repeat of CC16
      gene on chromosome 11q12-13 in relation to atopic and non-atopic asthma. Whereas
      variants of FcepsilonRIbeta at chromosome 11q13 show association with atopy and
      asthma, no significant association was found between asthma and CC16 genotypes
      irrespective of atopic status. These data support the candidacy of
      FcepsilonRIbeta rather than CC16 for the atopic asthma locus on chromosome 11q.

PMID- 9550364
TI  - ACTH receptor mutation in a girl with familial glucocorticoid deficiency.
AB  - Familial glucocorticoid deficiency (FGD) has long been recognised as a clinical
      entity, but molecular studies have so far been performed in only a few
      individuals. We describe a girl born to consanguineous Pakistani parents with
      clinical and biochemical features of FGD who is homozygous for the R146H mutation
      of the adrenocorticotropic hormone (ACTH) receptor gene. This mutation creates a
      new restriction enzyme site in the ACTH receptor gene, allowing accurate
      characterisation of the mutation without DNA sequencing. Our patient is the third
      child reported to be homozygous for the R146H mutation. Interestingly, she has a
      tall stature, a clinical finding reported in several children who have ACTH
      insufficiency and mutations of the ACTH receptor gene. We suggest that mutation
      analysis of the ACTH receptor gene be considered in children with clinical
      features of FGD and tall stature.

PMID- 9550365
TI  - 22q11.2 deletions in a series of patients with non-selective congenital heart
      defects: incidence, type of defects and parental origin.
AB  - Previous studies have indicated a wide spectrum of incidences of 22q11.2
      deletions in isolated and syndromic (sporadic or familial) cases of conotruncal
      heart defects, whereby the detection rate of the deletion varied from 65% in one
      study to 0 in another. We analysed 110 patients with non-selective syndromic or
      isolated non-familial congenital heart malformations by fluorescence in situ
      hybridization (FISH) using the D22S75 DiGeorge chromosome (DGS) region probe. A
      22q11.2 microdeletion has been detected in 9/51 (17.6%) syndromic patients. Five
      were of maternal origin and four of paternal origin. None of the 59 patients with
      isolated congenital cardiac defect had a 22q11.2 deletion. We compared the
      cardiac anomalies of our patients with a 22q11.2 deletion with those of
      previously published series and we describe types of congenital heart defects
      which appear to be often associated with a 22q11.2 deletion. The ability to
      detect such types of heart defects and to provide an early diagnosis of 22q11.2
      deletion is particularly relevant in very young infants, who often show only very
      mild expression of the otherwise well-characterized phenotypes of the
      DiGeorge/velo-cardio-facial syndrome (DG/VCFS).

PMID- 9550366
TI  - The 4q-syndrome: delineation of the minimal critical region to within band 4q31.
AB  - A consistent phenotype has been associated with deletion of the distal long arm
      of chromosome 4. An invariant requirement for the phenotype in cases described so
      far has been the deletion of material from within band 4q31 but few other cases
      have been described that further aid the delineation of the minimum critical
      region sufficient for the expression of the phenotype. We report a child with a
      small interstitial deletion within band 4q31 who exhibits most of the features of
      the established 4q-phenotype.

PMID- 9550367
TI  - VSD, hypospadias and normal psychomotor development in a patient with inv dup
      8(q13-q21.2).
AB  - This paper describes a patient with a de novo inverted duplication of chromosome
      8(q13-q21.2). He was born with a ventricular septum defect, glandular hypospadias
      and protruding ears. At the age of 5 1/2 years he had normal psychomotor
      development. Review of the literature on partial duplications of 8q reveals that
      the associated phenotype may be mild. Normal psychomotor development, as in our
      patient, however appears to be uncommon.

PMID- 9550369
TI  - Genetic variation among 129 substrains: practical consequences.
AB  - We designed a series of experiments to define the role of IFN-gamma in cellular
      interactions mediating graft rejection by assessing the rejection of H-Y
      disparate grafts in both ligand and receptor knockout mice and their control
      inbred strain. In the course of these studies it became apparent that neither
      knockout strain is histocompatible with the putative control and that the
      putative control is not histocompatible with either knockout strain. In the
      process of deducing why this might be so, it became apparent that the putative
      control is not an inbred strain of mouse. Thus, in the absence of rigorous
      genetic control, the utility of such knockout strains of mice for assessing the
      effects of cytokines and receptors in transplantation and autoimmunity is
      limited.

PMID- 9550368
TI  - Induction of IL-10 synthesis by human keratinocytes through CD23 ligation: a
      cyclic adenosine 3',5'-monophosphate-dependent mechanism.
AB  - Ligation of the low affinity receptor for IgE, CD23/Fc epsilonRII, in human
      keratinocytes (HK) and monocytes induces the synthesis of proinflammatory
      cytokines (IL-6 and TNF-alpha), partly under the dependence of cAMP and nitric
      oxide pathways. Moreover, CD23 ligation induces IL-10 production in human
      monocytes. Since synthesis of IL-10 by HK is still a matter of debate, we
      investigate whether keratinocytes could produce IL-10 upon CD23 stimulation.
      Here, our data show that CD23 ligation induces significant IL-10 synthesis in HK,
      a phenomenon inhibited by cAMP antagonists, but not by inhibitors of the nitric
      oxide pathway. Accordingly, cAMP agonist induced significant IL-10 synthesis by
      HK, while nitric oxide-releasing chemical did not. Treatment of HK with anti-IL
      10 mAb potentiated their CD23-mediated TNF-alpha synthesis. These data indicate
      that engagement of surface CD23 on human keratinocytes induces the synthesis of
      IL-10, which, in turn, down-regulates their proinflammatory response.

PMID- 9550370
TI  - Selective involvement of proteasomes and cysteine proteases in MHC class I
      antigen presentation.
AB  - CTL recognize peptides derived from protein Ags bound to MHC-class I molecules.
      Proteasomes probably participate in the generation of these peptide epitopes. We
      investigated the role of proteasomes in the presentation of endogenously
      synthesized short viral proteins. To this end, we employed proteasome and
      cysteine protease inhibitors and two closely related recombinant vaccinia viruses
      that code for 17- and 19-amino acid-long products encompassing murine CMV 9pp89
      epitope. Presentation of both minigene products required processing to shorter
      peptides and was independent of ubiquitination. Proteasomes were necessary for
      processing the 17-mer product, and cysteine proteases were not required. In
      contrast, the 19-mer product could be processed in parallel either by proteasomes
      or by cysteine proteases independently. These results highlight the diversity of
      alternative processing pathways even for short peptidic Ags, provide evidence for
      the involvement of cysteine proteases in MHC class I presentation, and show that
      cleavage by cysteine proteases is governed by sequences flanking the epitope.

PMID- 9550371
TI  - A role for Ras signaling in coreceptor regulation during differentiation of a
      double-positive thymocyte cell line.
AB  - Evidence suggests that the Ras/mitogen-activated protein kinase signaling pathway
      is required for positive selection of thymocytes. We have asked whether Ras
      activation is also sufficient to mediate changes in gene expression that are
      associated with positive selection. To accomplish this, we expressed a
      constitutively active form of Ras in the immature CD4+ 8+ DPK thymocyte cell
      line. DPK cells that express active Ras have reduced levels of CD8alpha and
      CD8beta at the level of cell surface protein and mRNA. These data provide
      evidence of a direct link between Ras signaling pathways and coreceptor
      regulation during positive selection. They also suggest that a sustained or
      potent Ras signal may play a critical role in directing thymocytes into the CD4
      lineage. DPK cells that express active Ras, however, were not fully
      differentiated, indicating that Ras signaling provides only a partial signal for
      double-positive thymocyte differentiation.

PMID- 9550372
TI  - Immunostimulatory effects of a plasmid expressing CD40 ligand (CD154) on gene
      immunization.
AB  - Interaction of CD40 with its ligand (CD154) can induce CD40-bearing APCs to
      express immune stimulatory accessory molecules that facilitate immune
      recognition. We evaluated whether a plasmid vector encoding CD154 (pCD40L) could
      influence the immune response to a transgene protein encoded by coinjected
      plasmid DNA. We found that coinjection of pCD40L in BALB/c mice enhanced the Ab
      response to beta-galactosidase induced by i.m. or intradermal injection of placZ,
      a plasmid DNA vector encoding beta-galactosidase. Furthermore, i.m. or
      intradermal coinjection of pCD40L with placZ enhanced the generation of CTL
      specific for P815 cells transfected with placZ. This study indicates that pCD40L
      can serve as a genetic adjuvant capable of augmenting humoral and cellular immune
      responses to Ags encoded by plasmid DNA expression vectors.

PMID- 9550373
TI  - Engagement of CD40 antigen with soluble CD40 ligand up-regulates peptide
      transporter expression and restores endogenous processing function in Burkitt's
      lymphoma cells.
AB  - Cells from the EBV-associated tumor, Burkitt's lymphoma (BL), are known to be
      highly inefficient at endogenous processing of class I-restricted CTL epitopes
      due to a consistent loss of peptide transporters (TAP) and MHC expression. We
      investigated the potential of CD40 engagement to up-regulate the expression of
      class I-processing genes and to enhance the immunogenicity of these malignant
      cells toward EBV-specific CTLs. Here we show that engagement of CD40 Ag with
      soluble CD40 ligand (CD40L) up-regulates TAP-1 and HLA class I expression on BL
      cells. More importantly, analysis of the Ag-processing function, using a
      recombinant vaccinia virus to transiently express the EBV nuclear Ags, revealed
      that CD40L-treated BL cells consistently processed endogenously synthesized viral
      Ags for recognition by HLA class I-restricted, virus-specific CTLs. These
      findings raise the possibility that CD40L treatment of tumor cells might be
      exploited in immunotherapeutic protocols.

PMID- 9550374
TI  - Evidence that the same gamma delta T cells respond during infection-induced and
      autoimmune inflammation.
AB  - Inflammatory responses are induced in both testes of a mouse following injection
      of Listeria monocytogenes into one testis. Although the uninjected testis
      contains no detectable bacteria, it undergoes an autoimmune attack. Normally, the
      testis lacks lymphocytes, but in the infected and autoimmune state, both gamma
      delta and alpha beta T cells are found as infiltrates. Here, we have examined the
      repertoire of the infiltrating gamma delta T cells, using two different methods,
      and found a high frequency of V gamma 6/V delta 1 gamma delta T cells in both
      infected and autoimmune testes. All of these expressed the invariant V gamma 6/V
      delta 1 TCR previously reported. However, secondary gamma and delta transcripts
      present within V gamma 6/V delta 1 hybridomas indicated nonclonality.
      Interestingly, some of these secondary transcripts were derived from gamma gene
      rearrangements not previously found in this gamma delta T cell subset, implying a
      difference in its origin. The increase in V gamma 6/V delta 1 cells observed here
      in both infected and autoimmune testes, together with our previous finding of a
      preferential response by the same subset in Listeria-infected liver, indicates
      that their response is triggered by the inflammation rather than by the
      infectious agent or because they are already resident in the tissue. We and
      others have previously reported that the presence of gamma delta T cells during
      certain inflammatory conditions correlates with less host tissue damage. This
      result, together with the evidence presented here, further implies that a
      response by the V gamma 6/V delta 1 subset in some way exerts a controlling
      influence on the host inflammatory response.

PMID- 9550376
TI  - Distinct biochemical signals characterize agonist- and altered peptide ligand
      induced differentiation of naive CD4+ T cells into Th1 and Th2 subsets.
AB  - We have recently shown that altered peptide ligands influence differentiation of
      CD4+ T cells into Th1 and Th2 subsets. In the present study, we have examined the
      biochemical signals in naive CD4+ T cells after priming with altered peptide
      ligand (APL) that correlate with differences in cytokine expression. Although we
      observed zeta-chain phosphorylation in APL-stimulated cells, other signaling
      events such as ZAP70 and Lnk phosphorylation are not initiated. This altered
      pattern observed in the early phosphorylation events correlates with a distinct
      Ca2+ mobilization pattern that characterizes APL-stimulated cells. By changing
      the calcium signaling environment during T cell priming, we present data
      indicating that qualitative differences in calcium mobilization are associated
      with differentiation of naive CD4+ T cells into Th1- and Th2-like effector
      subsets.

PMID- 9550375
TI  - VH gene replacement in hyperselected B cells of the quasimonoclonal mouse.
AB  - The primary repertoire of the quasimonoclonal mouse is monospecific. However,
      among peripheral B cells, there is a high frequency of variant cells with V(H)
      replacements, which are also hypermutated. We show in this work that these
      hyperselected cells expand in numbers as the animals increase in age, switch
      their isotypes, and with increasing age become the almost exclusive contributors
      to the pool of serum Ig. The fraction of such cells is higher in the peritoneum
      than in peripheral blood, supporting the view that the peritoneum is a site of
      production of nonspecific serum Ig. We have also isolated and partially sequenced
      the replacing V(H) gene segments from B220-positive, Id-negative cells, and mu
      negative, lambda-positive (i.e., switched) cells, and matched them with their
      germline counterparts. V(H) families are represented proportional to the number
      of members in the germline, a finding that is consistent with the idea that
      environmental Ag pressure maintains the germline repertoire of V gene segment.

PMID- 9550377
TI  - Resting B cells from autoimmune lupus-prone New Zealand Black and (New Zealand
      Black x New Zealand White)F1 mice are hyper-responsive to T cell-derived stimuli.
AB  - To determine whether B cells from New Zealand Black (NZB) and (New Zealand Black
      x New Zealand White)F1 (NZB/W) mice possess intrinsic defects that lead to
      altered immune responsiveness, we purified resting B cells from these mice and
      compared their surface phenotype and function with those of resting B cells
      isolated from BALB/c and DBA/2 nonautoimmune mouse strains. Flow cytometric
      analysis of freshly isolated resting B cells revealed that NZB and NZB/W resting
      B cells are conventional B2-type cells similar to their nonautoimmune
      counterparts. Despite this, resting B cells from young NZB and NZB/W mice express
      lower levels of CD23 on their surface and aberrant levels of intracellular IgM.
      Upon stimulation, resting B cells from young NZB and NZB/W mice demonstrate
      increased proliferation, IgM secretion, or enhanced expression of costimulatory
      molecules in response to a variety of different T cell-derived stimuli, including
      cytokines and signals generated through CD40. Therefore, B cell hyper
      responsiveness to T cell stimuli is immunodominant or codominant in NZB/W mice.
      Taken together, our results suggest that intrinsic B cell hyper-responsiveness
      may play a role in the pathogenesis of autoimmune disease in NZB and NZB/W mice.
      The increased clonal expansion of these B cells together with increased Ig
      production and enhanced costimulatory capacity serve to amplify the immune
      response. In the context of normal but incomplete T cell tolerance, B cell
      hyperresponsiveness to the limited signals provided by partially tolerant T cells
      may be sufficient to yield an autoantibody response.

PMID- 9550378
TI  - Anti-CD3 epsilon F(ab')2 fragments inhibit T cell expansion in vivo during graft
      versus-host disease or the primary immune response to nominal antigen.
AB  - This study was undertaken to distinguish between several mechanisms responsible
      for graft-vs-host disease (GVHD) protection in anti-CD3epsilonF(ab')2 fragment
      (Fr)-treated recipients: TCR down-modulation, deletion, failure of expansion, or
      anergy induction. To quantify alloreactive T cell expansion and function,
      thoracic duct lymphocytes (TDL) were analyzed. Sixfold fewer donor TDL T cells
      were recoverable from anti-CD3epsilonF(ab')2 Fr as compared with irrelevant
      F(ab')2 Fr-treated recipients at the time of peak T cell expansion in vivo.
      Kinetic analysis revealed that donor T cell expansion was inhibited and not
      simply delayed by anti-CD3epsilonF(ab')2 Fr. Similar proportions of TDL T cells
      in irrelevant and anti-CD3epsilonF(ab')2 Fr were undergoing apoptosis. Although
      TCR modulation was observed, donor TDL T cells had intact anti-host alloresponses
      as compared with irrelevant F(ab')2 Fr-treated recipients. Because donor CD4+ T
      cells are primarily responsible for GVHD in this model, an adoptive transfer
      system was used in which the function and kinetics of expansion of OVA-specific
      CD4+ TCR transgenic cells could be physically tracked. Relevant Fr severely
      blunted CD4+ TCR transgenic T cell clonal expansion after OVA administration.
      Nonviable transgenic and nontransgenic T cells were proportionally similar in OVA
      pulsed recipients, regardless of whether relevant or irrelevant F(ab')2 Fr were
      given. After discontinuing Fr, transgenic T cells were found to have intact in
      vitro OVA-specific responses. Our current and previous results suggest that
      reduced donor T cell expansion and T cell depletion both contribute to GVHD
      protection by anti-CD3epsilonF(ab')2 Fr. These data have implications for
      designing therapeutic approaches directed toward TCR targeting in humans.

PMID- 9550379
TI  - In vivo effects of T helper cell type 2 cytokines on macrophage antigen
      presenting cell induction of T helper subsets.
AB  - SJL mice provide an interesting paradigm to examine the role(s) of APC in the
      differential induction of Th1 and Th2 cells. Immunization of young male SJL mice
      results in the preferential induction of Th2 cells, whereas Th1 cells are induced
      in age-matched female or older male SJL mice. The absence of Th1 responses in
      young male mice is associated with in vivo IL-4 and IL-10 down-regulating Mac-3+
      APC priming of Th1 cells. The present report examines the mechanism of this APC
      dependent induction of Th subsets. Examination of the surface expression of MHC
      class II, adhesion molecules (CD11a, CD11b, CD48, CD54, and CD102) or
      costimulatory molecules (CD24, CD80, and CD86) showed no differences between male
      and female-derived Mac-3+ APC populations. In addition, no differences were
      detected in IL-1alpha, IL-1beta, IL-18, TNF-alpha, or IL-12 p35 mRNA expression.
      However, reduced expression of both IL-10 and IL-12 p40 mRNA were found in Mac-3+
      cells from male mice compared with those in Mac-3+ cells from female mice. Anti
      IL-4 or anti-IL-10 mAb treatment of young male donor mice eliminated the
      reduction of both IL-10 and IL-12 p40 mRNA, suggesting that the Th2 inducer
      phenotype is related to a decreased IL-12 secretion. Consistent with this idea,
      fewer IL-12 p40-secreting Mac-3+ cells were found in male mice compared with
      female mice, and treatment with rIL-12 resulted in the priming of Th1 cells in
      male mice. These data suggest that increased Th2 cytokines in vivo before
      encounter with Ag inhibit APC expression of IL-12, resulting in the preferential
      induction of Th2 cells in male SJL mice.

PMID- 9550380
TI  - Immunohistochemical analysis of in vivo patterns of TRAF-3 expression, a member
      of the TNF receptor-associated factor family.
AB  - An immunohistochemical approach was used to explore the in vivo expression of TNF
      receptor-associated factor 3 (TRAF-3), a putative signaling protein that binds to
      the cytosolic domains of CD30, CD40, and lymphotoxin-beta receptors. TRAF-3
      immunostaining was detected in many types of cells throughout the human body.
      TRAF-3 immunostaining was only rarely present in thymocytes but was found in the
      thymic epithelioreticular cells. Lymphocytes in the bone marrow were also
      typically TRAF-3 immunonegative, whereas myeloid progenitor cells and
      megakaryocytes were often TRAF-3 positive. Peripheral blood lymphocytes were
      mostly TRAF-3 immunonegative, while granulocytes were TRAF-3 immunopositive.
      Monocytes were strongly immunostained for TRAF-3, but macrophages in nodes
      typically contained little or no TRAF-3 immunoreactivity. Some lymphocytes within
      the germinal centers of secondary lymphoid follicles in normal and reactive nodes
      were TRAF-3 immunopositive, as were occasional interfollicular lymphocytes in the
      T cell regions of these organs, but most lymphocytes appeared to be TRAF-3
      immunonegative or stained only weakly. Plasma cells, however, were strongly TRAF
      3 positive. Stimulation of PBLs with anti-CD3 Ab induced marked increases in the
      steady state levels of TRAF-3 protein in vitro as determined by immunoblotting,
      while levels of TRAF-2 were unchanged, implying a dynamic regulation of TRAF-3
      expression. The findings establish for the first time the cell type- and
      differentiation-specific patterns of expression of a member of the TRAF family of
      proteins.

PMID- 9550382
TI  - TCR V alpha 24 and V beta 11 coexpression defines a human NK1 T cell analog
      containing a unique Th0 subpopulation.
AB  - Murine NK1 natural T (NT) cells are a population of alphabeta T cells that
      express NK cell receptors and an invariant TCR rearrangement. These cells rapidly
      produce large amounts of IL-4 upon activation and have been suggested to promote
      Th2 differentiation. We sought to determine whether a human NK1 T cell analogue
      could be detected in PBMC, and if so, characterize the TCR usage, cytokine
      expression, and surface phenotype of this subset. Using flow cytometry, we have
      demonstrated a distinct population of V alpha24+, V beta11+, CD56+ T cells
      consistent with NT cells. Upon sequencing, these cells expressed an invariant V
      alpha24-J alphaQ TCR rearrangement, verifying their identity as a human NK1 T
      cell analogue. NT cells demonstrated increased frequencies of both IFN-gamma and
      IL-4 production. Strikingly, 30 to 45% of CD4+ NT cells expressed IL-4, a sixfold
      greater frequency than that seen in mainstream CD4+ alphabeta T cells. Contrary
      to the pattern seen with mainstream T cells, virtually all IL-4-producing NT
      cells coexpressed IFN-gamma, indicating that this subset of NT cells has a unique
      Th0 phenotype. These data establish that V alpha24+ NT cells are a potent source
      of IL-4 and as such, may play a role in Th2 priming in human immune responses.
      This work demonstrates that human NT cells can be phenotypically identified and
      functionally studied in the blood of healthy or diseased subjects.

PMID- 9550381
TI  - Antigen presentation by epithelial cells induces anergic immunoregulatory CD45RO+
      T cells and deletion of CD45RA+ T cells.
AB  - The immunoregulatory effects of alloantigen presentation by tissue parenchymal
      cells to resting peripheral blood CD4+ T cells was investigated. Coculture of
      CD45RO+ (memory) and CD45RA+ (naive) T lymphocytes with primary cultures of MHC
      class II-expressing epithelial cells rendered both populations of T cells
      hyporesponsive to a subsequent challenge by the same MHC molecule expressed on
      EBV-transformed lymphoblastoid B cell lines. However, the mechanisms responsible
      for the allospecific hyporesponsiveness were distinct. For the CD45RO+ T cells,
      responsiveness was restored by subsequent culture in the presence of IL-2; the
      addition of IL-2 had no effect on the reactivity of the CD45RA+ T cells. In
      contrast, the naive T cells were protected from the induction of
      nonresponsiveness by the presence of a neutralizing anti-CD95 Ab during the
      culture with thyroid follicular cells. In addition, the hyporesponsive CD45RO+ T
      cells effected linked suppression, in that they inhibited proliferation against a
      third-party DR alloantigen when the third-party alloantigen was coexpressed with
      the DR Ag against which hyporesponsiveness had been induced. These results
      suggest that recognition of Ag by T cells on tissue parenchymal cells plays an
      important role in the maintenance of peripheral T cell tolerance, inducing
      nonresponsiveness in naive and memory T cells by distinct mechanisms.

PMID- 9550383
TI  - Cyclic-AMP modulates downstream events in CD40-mediated signal transduction, but
      inhibition of protein kinase A has no direct effect on CD40 signaling.
AB  - The role of cAMP/protein kinase A (PKA) in CD40 signal transduction is
      controversial, with evidence both for and against its importance. In this study
      we have used a tetracycline-repressible expression system to reversibly express a
      dominant-negative form of the PKA regulatory subunit type I (PKA-R(G324D)) in a B
      lymphoma line, M12. Expression of PKA-R(G324D) in M12 lymphomas inhibits both
      cAMP-mediated growth inhibition and cAMP-mediated induction of B7-2. This
      inhibition is reversed by tetracycline treatment of the cells to turn off
      inhibitor expression. In contrast, the expression of the PKA-R(G324D) subunit has
      no effect on CD40-mediated growth inhibition in M12 cells, nor on CD40-mediated
      induction of B7-1, CD23, Fas, ICAM-1, or LFA-1. Thus, our data do not support a
      direct role for cAMP/PKA in CD40-mediated signal transduction. However, we do
      observe that cAMP can regulate CD40 signaling both positively and negatively.
      Cyclic-AMP synergizes with CD40-mediated B7-1 induction in M12 lymphomas, while
      inhibiting CD40-mediated CD23, Fas, and ICAM-1 induction.

PMID- 9550384
TI  - Early and late events in Fc epsilon RI signal transduction in human cultured mast
      cells.
AB  - Protein tyrosine phosphorylation and other biochemical events have been shown to
      occur after cross-linking of Fc epsilonRI in rodent mast cells. To investigate
      the mechanism of Fc epsilonRI signal transduction in human mast cells, we used
      human cultured mast cells (HCMC) generated from cord blood cells in the presence
      of recombinant human stem cell factor and IL-6. We found that on cross-linking of
      Fc epsilonRI: 1) HCMC released histamine; 2) rapid tyrosine phosphorylation of
      multiple cellular substrates, including Syk, HS1, c-Cbl, ERK-1, and ERK-2, was
      observed; 3) intracellular Ca2+ and inositol phosphate production were increased
      within the first minute after Fc epsilonRI cross-linking; and 4) genistein, a
      tyrosine kinase inhibitor, inhibited both protein tyrosine phosphorylation and
      histamine release in a dose-dependent manner. These results were consistent with
      previous studies in rodent mast cells. In contrast, no tyrosine phosphorylation
      of phospholipase C gamma1 and Btk (Bruton's tyrosine kinase) were observed in our
      experimental conditions. These results suggest that the greater part of the early
      and late signaling events in HCMC is similar to those obtained with rodent mast
      cells and indicated that the requirement of tyrosine phosphorylation in the
      activation process of each of the signaling molecules might be different in HCMC
      and rodent mast cells. Our finding indicates that HCMC may be useful for analysis
      of Fc epsilonRI-mediated signal transduction in human mast cells.

PMID- 9550385
TI  - Pharmacological control of antigen responsiveness in genetically modified T
      lymphocytes.
AB  - A chimeric TCR gene, comprising an anti-hapten single-chain Ab variable fragment
      fused to the transmembrane and cytoplasmic regions of the human TCR zeta-chain,
      was used to determine whether the tetracycline-regulatable system could be used
      to regulate gene expression in T cells. Jurkat T cells were stably transfected
      with a single vector encoding the tetracycline trans-activator protein,
      controlled by a constitutive promoter, and the chimeric TCR, under the control of
      a trans-activator protein-responsive promoter. In the absence of tetracyclines,
      the transfected T cells were shown to express the chimeric receptor on the cell
      surface and could be activated by its cognate Ag, leading to the secretion of IL
      2. When the cells were exposed to increasing concentrations of tetracyclines,
      surface expression of the chimeric receptor was suppressed in a dose-dependent
      manner, and this suppression was sufficient to result in complete loss of
      responsiveness to the targeted Ag. Prolonged suppression of trans-gene expression
      for up to 7 days was observed after doxycycline was removed from the cultures,
      but eventual recovery of surface expression was complete, and the absolute time
      to recovery was directly proportional to the initial concentration of the drug.
      Pharmacologic control of trans-gene expression in gene-modified T cells will not
      only facilitate new approaches to the study of different aspects of T cell
      biology, but will also provide the basis for new gene therapy strategies.

PMID- 9550386
TI  - Proteasome activity limits the assembly of MHC class I molecules after IFN-gamma
      stimulation.
AB  - For an effective CD8+ cytotoxic T cell response to occur during infection, MHC
      class I molecules must be loaded with antigenic peptides in the endoplasmic
      reticulum. The cytosolic factor responsible for peptide generation is believed to
      be the proteasome, with the TAP heterodimer mediating peptide transport into the
      endoplasmic reticulum. However, the rate-determining step(s) in this
      intracellular pathway of Ag presentation is currently unresolved. The
      availability of a specific and irreversible proteasome inhibitor called
      lactacystin has enabled us to determine the amount of proteasomes required for
      the peptide loading of MHC class I molecules in four cell types. In the absence
      of the IFN-gamma-inducible proteasome subunits LMP2 and LMP7, the trypsin-like
      (but not the chymotrypsin-like) activity of the proteasome is directly related to
      MHC class I peptide loading. However, IFN-gamma stimulation or assimilation of
      catalytic LMP2 and LMP7 subunits into proteasomes causes both chymotrypsin- and
      trypsin-like activities of the proteasome to become limiting for the loading of
      class I molecules. Our data suggest that upon full IFN-gamma stimulation, peptide
      supply by the proteasome is the limiting step in the assembly of MHC class I
      polypeptides. This mechanism may enable the cell to prevent competition between
      novel Ags and the pool of endogenous proteins for binding to MHC class I
      molecules.

PMID- 9550387
TI  - Mouse IL-1 receptor antagonist isoforms: complementary DNA cloning and protein
      expression of intracellular isoform and tissue distribution of secreted and
      intracellular IL-1 receptor antagonist in vivo.
AB  - IL-1R antagonist (IL-1Ra) is a competitive inhibitor of the binding of IL-1 to IL
      1R. IL-1Ra refers to two different proteins derived from the same gene by
      alternate splicing of two different first exons. One protein contains a leader
      sequence and is secreted (sIL-1Ra), whereas the other remains intracellular (icIL
      1Ra). We describe the cloning of mouse icIL-1Ra cDNA, the expression of the
      recombinant mouse icIL-1Ra protein, and the tissue distribution of sIL-1Ra and
      icIL-1Ra mRNA and of icIL-1Ra protein in control and LPS-injected mice. As
      described in the human and the rabbit, mouse icIL-1Ra protein differs from mature
      mouse sIL-1Ra protein by seven amino acids at the amino terminus. In addition,
      human and mouse icIL-1Ra are 77% identical. Regulation of IL-1Ra isoforms was
      examined in normal mice and after LPS injection. Circulating levels were
      undetectable in control mice, but were strongly increased 4 h after LPS
      injection. Using a ribonuclease protection assay (RPA), we found that icIL-1Ra
      mRNA was expressed constitutively in skin and in LPS-stimulated RAW 264.7 murine
      macrophages. Consistent with the RNA studies, Western blot analysis showed that
      murine icIL-1Ra protein was constitutively expressed in skin and in LPS
      stimulated RAW 264.7 cells. In contrast, sIL-1Ra mRNA was not detected by RPA in
      tissues of control mice, but was strongly up-regulated in the lung, spleen, and
      liver after LPS injection. Using RPA, primer extension assay and 5' rapid
      amplification of cDNA ends, we were able to demonstrate the presence of different
      transcription start sites for murine sIL-1Ra mRNA.

PMID- 9550388
TI  - Single amino acid mutations in the murine MHC class II A beta cytoplasmic domain
      abrogate antigen presentation.
AB  - Class II MHC molecules are heterodimeric transmembrane glycoproteins that
      function in the presentation of Ag to CD4+ T cells. Deletion of the cytoplasmic
      domains of the murine class II A alpha- and A beta-chains has previously been
      shown to diminish Ag presentation and abrogate rejection of class II-transfected
      tumor cells. To examine the contributions of individual amino acid residues of
      the A beta cytoplasmic domain to Ag presentation and tumor rejection, we have
      produced a series of cell lines expressing A beta class II molecules with site
      directed mutations. An A beta(k) cDNA was constructed with mutations in the five
      conserved amino acid residues, Q224, K225, L235, L236, and Q237 (delta5). In
      addition, cDNA were produced in which alanine was individually substituted for A
      beta(k) cytoplasmic domain residues 224 through 237 or doubly substituted at
      residues G226 and P227 or L235 and L236. These mutant cDNAs were individually
      cotransfected with wild-type A alpha cDNA into the class II-negative M12.C3 B
      lymphoma and Sal sarcoma cell lines. As was previously reported for transfectants
      lacking the entire A beta(k) cytoplasmic domain, the delta5 M12.C3 transfectant
      could not effectively present Ag to an autoreactive Ak-restricted T cell hybrid,
      and the delta5 Sal transfectant was not rejected when inoculated into syngeneic
      hosts. A finer analysis revealed that alteration of the individual residue Q224
      or the two residues G226 and P227 abrogated Ag presentation in vitro, while
      mutation of G226 diminished tumor rejection in vivo. Thus, the function of the A
      beta cytoplasmic domain in Ag presentation both in vitro and in vivo can be
      disturbed by mutation of single amino acid residues.

PMID- 9550389
TI  - Effects of CD28 costimulation on long-term proliferation of CD4+ T cells in the
      absence of exogenous feeder cells.
AB  - In this report, conditions for prolonged in vitro proliferation of polyclonal
      adult CD4+ T cells via stimulation with immobilized anti-CD3 plus anti-CD28 have
      been established. CD4+ cells maintained exponential growth for more than 60 days
      during which a total 10(9)- to 10(11)-fold expansion occurred. Cell cultures
      exhibited cyclical changes in cell volume, indicating that, in terms of
      proliferative rate, cells do not have to rest before restimulation. Indeed,
      electronic cell size analysis was the most reliable method to determine when to
      restimulate with additional immobilized mAb. The initial approximately 10(5)-fold
      expansion was autocrine, occurring in the absence of exogenous cytokines or
      feeder cells. Addition of recombinant human IL-2 after the initial autocrine
      expansion resulted in continued exponential proliferation. Phorbol ester plus
      ionomycin also induced long-term growth when combined with anti-CD28 stimulation.
      Analysis of the T cell repertoire after prolonged expansion revealed a diverse
      repertoire as assessed by anti-TCR Vbeta Abs or a PCR-based assay. Cytokines
      produced were consistent with maintenance of both Th1 and Th2 phenotypes;
      however, the mode of CD3 and CD28 stimulation could influence the cytokine
      secretion pattern. When anti-CD3 and anti-CD28 were immobilized on the same
      surface, ELISAs on culture supernatants revealed a pattern consistent with Th1
      secretion. Northern analysis revealed that cytokine gene expression remained
      inducible. Spontaneous growth or cell transformation was not observed in more
      than 100 experiments. Together, these observations may have implications for gene
      therapy and adoptive immunotherapy. Furthermore, these culture conditions
      establish a model to study the finite lifespan of mature T lymphocytes.

PMID- 9550390
TI  - Role for IL-15/IL-15 receptor beta-chain in natural killer 1.1+ T cell receptor
      alpha beta+ cell development.
AB  - Mouse TCR alphabeta+ cells expressing NKR-P1 (NK1+ T cells in the C57BL/6 strain)
      are classified as a unique subset that require beta2m-associated, MHC class I
      like molecules for development and preferentially express particular V beta and V
      alphaJ domains of the TCR. We show here that NK1+ T cells express the IL-2R
      beta/IL-15R beta that is normally present on conventional NK cells, but not T
      cells. In mice lacking IL-2R beta/IL-15R beta chain, the number of NK1+ T cells
      is dramatically reduced. However, in IL-2-deficient mice, NK1+ T cells develop
      normally. Moreover, NK1+ T cells proliferate upon stimulation by IL-15, and the
      proliferation is blocked by the addition of anti-IL-2R beta/IL-15R beta Abs.
      Collectively, our data indicate that NK1+ T cells require IL-2R beta/IL-15R beta
      chain in an IL-2-independent manner and demonstrate that IL-15 plays a crucial
      role during development.

PMID- 9550391
TI  - Maternal immunization with a soluble TCR-Ig chimeric protein: long term, V beta-8
      family-specific suppression of T cells by maternally transferred antibodies.
AB  - Maternal transfer of TCR clonotypic Ab protected young NOD mice against the
      adoptive transfer of diabetes by the BDC 2.5 T cell clone. The effect of maternal
      anti-TCR Vbeta-8 Ab on T cell development and function has now been investigated.
      SJL/J mice, which lack TCR Vbeta-8, were immunized with soluble, chimeric D10 TCR
      IgG1 containing Vbeta-8.2. The (SJL/J x AKR/J) F1 offspring of immunized female
      SJL/J mice were severely depleted of peripheral T cells bearing Vbeta-8 until 11
      to 17 wk of age. The loss of Vbeta-8 expression did not appear to be due to
      modulation of cell surface TCR. Since the Vbeta-8+ T cell population was
      unperturbed in the (AKR/J x SJL/J) F1 offspring of D10 TCR-IgG1-immunized AKR/J
      mothers making D10 clonotypic Ab, the effect was immunologically specific. The
      deletion of Vbeta-8+ T cells had functional consequences. In the in vitro
      response to the superantigen, staphylococcal enterotoxin B, the usually observed
      participation of Vbeta-8.2+ T cells was largely suppressed, whereas the
      recruitment of Vbeta-3+ T cells remained unaltered. In control mice, T cell
      responses to the 134- to 146-residue peptide of conalbumin (pCA(134-146)) were
      biased toward use of Valpha-2/Vbeta-8.2 TCR. In D10 TCR-IgG1 maternally immunized
      (SJL x AKR/J) F1 mice, the T cell responses to pCA(134-146) were suppressed, and
      T cell lines derived from these in vitro were devoid of Vbeta-8.2 expression.
      With an increased understanding of TCR V gene usage in autoimmune diseases,
      similar strategies for the depletion of autoreactive T cells may become feasible
      in humans.

PMID- 9550392
TI  - IgA plasma cells in vascular tissue of patients with Kawasaki syndrome.
AB  - The etiology and pathogenesis of Kawasaki syndrome (KS) remain unknown. Clinical
      and epidemiologic features of KS are consistent with an infectious cause. To
      search for an etiologic agent of KS, a phage cDNA expression library was
      constructed from the aorto-iliac junction of a patient with fatal acute KS and
      screened with convalescent KS serum followed by anti-human Ig. Unexpectedly, 0.1%
      of the clones in the library react with anti-human Ig, indicating the presence of
      many Ig-producing B lymphocytes in the vasculitic tissue. To confirm this finding
      and to determine the isotypes produced, frozen vascular tissue sections from the
      patient and paraffin sections from coronary arteries from six additional patients
      with fatal acute or subacute KS were incubated with Abs to Ig isotypes.
      Histopathology of the tissues revealed the presence of many plasma cells in the
      inflammatory infiltrate. IgA was the predominant isotype produced in vascular
      tissue in all seven KS patients. IgM- and IgG-producing cells were less often
      detected. We conclude that there is a marked plasma cell response within the
      vasculitic tissue in KS, with unusual IgA production locally in this nonlymphoid,
      nonmucosal tissue. We suggest that the prominence of IgA plasma cells in the
      vascular infiltrate in the early, acute, and subacute stages of KS indicates an
      Ag-driven immune response to an etiologic agent with a respiratory or
      gastrointestinal portal of entry and speculate that this unusual immune response
      is integral to the pathogenesis of the illness.

PMID- 9550393
TI  - Strength of TCR signal determines the costimulatory requirements for Th1 and Th2
      CD4+ T cell differentiation.
AB  - Differentiation of naive CD4 T cells into cytokine-secreting effector Th1 and Th2
      cells is influenced by several factors. We have previously reported that the
      affinity of antigen for TCR and antigen dose can influence the differentiation of
      Th1 and Th2 cells. Several in vitro and in vivo models have demonstrated a role
      for the costimulatory molecules, B7-1 (CD80) and B7-2 (CD86), in the generation
      of distinct effector T cell responses. To determine whether the strength of TCR
      signaling controls the involvement of CD28 costimulation in selective CD4 T cell
      differentiation, naive CD4 T cells bearing a transgenic TCR are primed by a weak
      or strong TCR signal (signal 1) in the presence or absence of B7 costimulatory
      molecules (signal 2). In this system, IL-4-producing Th2 cells are generated by
      priming with a weak but not a strong TCR signal. Th2 cell differentiation is
      dependent on CD28/B7 interactions in that disruption of CD28/B7 interactions
      inhibits the priming of Th2 cells and cross-linking CD28 with anti-CD28 antibody
      augments the priming of Th2 cells. In contrast, however, IL-4-producing Th2 cells
      cannot be generated by priming with a strong TCR signal even in the presence of
      strong costimulation or high doses of IL-2. Thus, our results suggest that naive
      CD4 T cells are receptive to CD28-dependent IL-4 production only if they receive
      a weak TCR signal.

PMID- 9550394
TI  - IL-1 beta-converting enzyme (ICE) is present and functional in human alveolar
      macrophages: macrophage IL-1 beta release limitation is ICE independent.
AB  - Tissue macrophages readily produce intracellular pro-IL-1beta in response to
      stimuli such as LPS, but are limited in mature IL-1beta release compared with
      blood monocytes. The mechanism of this IL-1beta control may provide important
      insights into the physiology of IL-1beta at the tissue level. Since it has been
      hypothesized that IL-1beta processing by the IL-1beta-converting enzyme (ICE)
      regulates IL-1beta release, we compared human alveolar macrophages and human
      blood monocytes for relative ICE expression and activation. Using immunoblots and
      enzyme-linked immunoassay for ICE, we demonstrate that alveolar macrophages do
      not differ from blood monocytes in antigenic p45 ICE. Furthermore, an indirect
      assay for functional ICE documents similar ICE activities in both monocytes and
      alveolar macrophages, i.e., similar concentrations of soluble synthetic ICE
      inhibitor (IC50 values of 0.3 +/- 0.01 and 0.6 +/- 0.2 microM, respectively) are
      required to block mature IL-1beta generation. However, as has been reported for
      THP-1 myelomonocytic cells, neither alveolar macrophages nor blood monocytes
      contain directly quantifiable levels of functional ICE forms (p22/p20 and p10)
      when assayed by immunoblots or by a sensitive capture ELISA that uses an
      irreversible, biotinylated ICE inhibitor. These findings document that the
      macrophage limitation in mature IL-1beta release is not due to a lack of ICE or
      to an inability to activate ICE. Finally, using a staged release assay, the time
      to half-maximum mature IL-1beta release is significantly depressed in macrophages
      compared with that in monocytes. Taken together, these findings suggest that
      macrophage IL-1beta export is regulated independently of ICE activation.

PMID- 9550396
TI  - Exploiting the difference between intrinsic and extrinsic kinases: implications
      for regulation of signaling by immunoreceptors.
AB  - When receptors must interact with an extrinsic kinase to initiate signaling, the
      kinase can play a regulatory role that is not available to intrinsic receptor
      kinases. Whether control is exercised at this level depends critically on the
      amount of kinase available to the receptors and on the potential for
      redistribution of the kinase during signaling. This study demonstrates that the
      high affinity receptor for IgE (Fc epsilonRI) on rat basophilic leukemia cells is
      regulated by its initiating kinase. We present a mathematical model that allows
      for the reversible recruitment of extrinsic kinases to phosphorylated
      immunoreceptor tyrosine-based activation motifs. By comparing model predictions
      to experimental time courses of phosphorylation, we infer that Lyn is limiting,
      that redistribution occurs after receptors are aggregated, and that the
      redistribution makes the relationship between tyrosine phosphorylation and
      receptor aggregation nonlinear.

PMID- 9550395
TI  - Human thymocytes become lineage committed at an early postselection CD69+ stage,
      before the onset of functional maturation.
AB  - Mature functional CD4 or CD8 single positive (SP) thymocytes differentiate from
      immature CD4+ 8+ double positive (DP) precursors through a process of positive
      selection and terminal differentiation. To study CD4/CD8 lineage commitment,
      human postselection CD69+ thymocytes were separated into distinct subpopulations
      based on the differential expression of CD27, CD1, and CD45RA/RO. We demonstrate
      that these CD69+ subpopulations represent transitional stages of a common
      differentiation pathway during which CD69+ thymocytes that are initially CD27-
      CD1+ CD45RA- will sequentially up-regulate CD27, down-regulate CD1, and
      eventually acquire CD45RA upon maturation. Examination of CD4 and CD8 expression
      on these CD69+ subsets identified an early postselection CD69+ CD27- CD4SP
      population that gives rise to both CD4SP and CD8SP mature T cells when cultured
      in mouse thymus organs. In addition, a CD4+ 8+ DP population was identified that
      is CD69+ and CD27+, which only gives rise to CD8SP progeny upon culture. Although
      these results suggest that development of CD4SP and CD8SP cells may proceed
      through distinct intermediates, examination of active biosynthesis of CD4 and CD8
      by the various subsets demonstrated that cells that have selectively terminated
      CD4 synthesis are already present in the CD27- CD4SP and CD27+ DP populations
      before culture. These data support a model of thymocyte differentiation whereby
      the decision of thymocytes to differentiate into one or the other lineage occurs
      concomitantly with, or very soon after, acquisition of CD69 and before the cells
      acquire CD27, down-regulate CD1, or acquire functional properties.

PMID- 9550397
TI  - Activation-related differences in HLA class I-bound peptides: presentation of an
      IL-1 receptor antagonist-derived peptide by activated, but not resting, CD4+ T
      lymphocytes.
AB  - We have compared by reverse phase HPLC the set of peptides eluted from HLA class
      I molecules in resting and activated CD4+ Jurkat cells. Two peptides were
      identified that are presented de novo upon activation. After sequencing, one of
      these peptides turned out to derive from IL-1R antagonist (IL-1Ra). In keeping
      with this observation, we found that activated, but not resting, Jurkat cells
      express IL-1Ra. These data indicate that activation of a CD4+ T cell line may
      result in presentation of peptides derived from proteins expressed de novo after
      activation. Since IL-1Ra was not known to be expressed by cells of the T lineage,
      we also investigated its pattern of expression in normal T lymphocytes. Reverse
      transcriptase-PCR analyses allowed us to demonstrate that IL-1Ra is expressed
      upon activation by normal CD4+ lymphocytes from peripheral blood and by
      thymocytes, but not by CD8+ T cells. Interestingly, of the two forms of IL-1Ra
      that have been detected in different cell lineages, the intracellular one and the
      secreted one, only the former is expressed by activated CD4+ T cells.

PMID- 9550398
TI  - CD40 and IL-4 regulate murine CD27L expression.
AB  - It is well known that interactions between accessory molecules on T cells and
      their ligands on APC play a key role in regulating T cell effector activity. The
      factors controlling the expression of these molecules are thus important
      determinants in the outcome of T cell activation. We have examined the expression
      of the murine ligand for CD27, a costimulatory molecule on T cells. Evidence is
      shown that CD27L is expressed at a low level on resting B cells but not on T
      cells, and that activation of B cells by culture with LPS or anti-IgM Ab
      increases the expression of CD27L. Interestingly, coligation of CD40 down
      regulates CD27L on LPS-activated B cells but not on anti-Ig-activated cells.
      These findings suggest that costimulation via the CD27-CD27L pathway may be
      limited to interactions involving Ag-specific B cells, i.e., B cells specifically
      activated via their Ig receptors. In addition, testing a spectrum of different
      cytokines indicated that IL-4 and TGF, but not IL-2, IL-10, or IFN-gamma,
      prevented up-regulation of CD27L expression on activated B cells even when
      activation was induced by Ig signaling. The capacity of IL-4 to prevent CD27L
      expression could thus serve to limit CD27-CD27L interactions to Th1-type T cell
      responses.

PMID- 9550399
TI  - CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral
      responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes.
AB  - Viral, bacterial, protozoal, and cancer-associated Ags elicit strong responses in
      human gammadelta T lymphocytes. The majority of these cells in the peripheral
      blood express the Vgamma9Vdelta2-encoded TCR and recognize nonpeptidic
      phosphoantigens without an apparent MHC restriction. We have shown that
      Vgamma9Vdelta2 T cells express the inhibitory CD94/NKG2 receptor for HLA class I
      molecules. The anti-CD94 mAb inhibits 1) the Vgamma9Vdelta2 T cell proliferation
      in response mycobacterial phosphoantigens and 2) the HIV-induced Vgamma9Vdelta2 T
      cell expansion. Vgamma9Vdelta2 T cells stimulated with nonpeptidic mycobacterial
      antigens produce IFN-gamma and TNF-alpha. Signaling through the CD94/NKG2
      receptor interferes with the synthesis of these cytokines. The CD94/HLA class I
      interaction is also involved in the cytotoxic activity of Vgamma9Vdelta2 T cells.
      The Vgamma9Vdelta2 T cell regulation through the CD94 receptor may be important
      for the potentially dual function in innate immunity, i.e., 1) NK-like and 2) TCR
      ligand-induced cytolytic activities.

PMID- 9550400
TI  - Independent regulation of cutaneous lymphocyte-associated antigen expression and
      cytokine synthesis phenotype during human CD4+ memory T cell differentiation.
AB  - Although considerable attention has been paid to the development of cytokine
      synthesis heterogeneity during memory T cell differentiation, little information
      is available on how this function is coregulated with homing receptor expression.
      The development of skin-homing, CD4+ memory T cells in the human provides an
      excellent model for such investigation, since 1) the skin supports both Th1- and
      Th2-predominant responses in different settings, and 2) the skin-homing
      capability of human memory T cells correlates with and appears to depend on
      expression of the skin-selective homing receptor cutaneous lymphocyte-associated
      Ag (CLA). In this study, we used multiparameter FACS analysis to examine
      expression of CLA vs IFN-gamma, IL-4, and IL-2 synthesis capabilities among fresh
      peripheral blood CD4+ memory T cells, and Th1 vs Th2 memory T cells generated in
      vitro from purified CD4+ naive precursors by cyclic activation in polarizing
      culture conditions. Among normal peripheral blood T cells, CLA expression was
      essentially identical among the IFN-gamma- vs IL-4-producing CD4+ memory subsets,
      clearly indicating the existence of in vivo mechanisms capable of producing both
      Th1 vs Th2 skin-homing T cells. In vitro differentiation of naive CD4+ T cells
      confirmed the independent regulation of CLA and all three cytokines examined,
      regulation that allowed differential production of IFN-gamma-, IL-4-, and IL-2
      producing, CLA+ memory subsets. These studies also 1) demonstrated differences in
      regulatory factor activity depending on the differentiation status of the
      responding cell, and 2) revealed CLA expression to be much more rapidly
      reversible on established memory cells than cytokine synthesis capabilities.

PMID- 9550401
TI  - Identification of shared tumor-associated antigen peptides between two
      spontaneous lung carcinomas.
AB  - CTLs recognize antigenic peptides bound to MHC class I Ags on the cell surface of
      tumor cells. Tumor-associated Ag (TAA) peptides are 8 to 10 amino acids long and
      can be derived from normal, mutated, or viral proteins. The majority of T cell
      defined Ags have been identified in human melanoma cells. These were shown to be
      commonly expressed by different allogeneic melanomas that share the same MHC
      molecule. We have recently isolated Kb-restricted TAA peptides, which are
      mutations of the gap junction protein connexin 37, from the spontaneous C57BL/6
      Lewis lung carcinoma (3LL). These peptides, named MUT 1 and MUT 2, serve as CTL
      epitopes and can induce CTL activity in vivo. Using CTL cross-reaction assays,
      peptide extraction, HPLC fractionation, and reverse transcriptase-PCR
      amplification, we show that clones of another spontaneous C57BL/6 lung carcinoma,
      CMT 64, share TAA peptides with the 3LL carcinoma. Vaccination with synthetic MUT
      1 or MUT 2 induces CTLs that efficiently lyse CMT 64-derived clones, protects
      mice from CMT 64 metastasis, and affords therapy of established CMT 64
      metastases. Hence, shared CTL epitopes exist between two spontaneous murine lung
      carcinomas.

PMID- 9550402
TI  - Deoxyribonucleic acid vaccines encoding antigens with rapid proteasome-dependent
      degradation are highly efficient inducers of cytolytic T lymphocytes.
AB  - We generated plasmid expression vectors encoding ubiquitin and beta-galactosidase
      (beta-gal) with different intervening amino acids, allowing for the production of
      processed protein products that have either stabilizing or destabilizing residues
      at their N-termini. P815 cells transfected with plasmids encoding beta-gal with a
      destabilizing N-terminus did not have detectable expression beta-gal unless they
      were treated with inhibitors specific for the proteasome. Inhibitors of other
      proteolysis pathways had no such effect. Nevertheless, transfectants expressing
      beta-gal with different amino acid residues were equally sensitive to cytolysis
      by a CTL clone specific for a beta-gal peptide presented in the context of H-2Ld.
      In contrast to vectors encoding native beta-gal, plasmid vectors encoding beta
      gal with a destabilizing residue did not induce detectable anti-beta-gal Abs when
      injected into skeletal muscle of BALB/c mice. However, such vectors were
      significantly more effective than vectors encoding native beta-gal or beta-gal
      with a stabilizing residue in stimulating CTL specific for P13.2, a lacZ
      transfectant of P815. We conclude that incorporation of strategies that enhance
      proteasome-dependent degradation may generate DNA vaccines that are more
      effective in inducing cellular immunity against targeted Ags.

PMID- 9550403
TI  - Complex origin of the HLA-DR10 haplotype.
AB  - The region of the HLA complex occupied by the DRB genes has undergone many
      rearrangements in the course of primate evolution. The rearrangements have
      produced a number of haplotypes differing from one another in the number and
      composition of the DRB genes. Some of the rearrangements also affected the DRB
      genes themselves. Selective intron sequencing has revealed the DR10 haplotype to
      be composed of at least three segments, each of different origin. The haplotype
      carries three DRB genes (gene fragments): DRB1*10, DRB6, and DRB9. The 5' end of
      the DRB1*10 gene, from the promoter region to a site in intron 1 approximately
      500 bp from the beginning of exon 2, is derived from a DRB1*03-like gene. The
      segment of the DR10 haplotype encompassing the rest of the DRB1*10 gene and
      extending to the region between the DRB1 and DRB6 genes is of independent origin;
      it diverged from other DRB genes (DRB1*01 and DRB1*03) approximately 30 million
      years ago. Finally, the third segment encompassing the remainder of the DR10
      haplotype is derived from a DR1-like haplotype. Since the functional part of the
      DR10 haplotype is of independent origin, there is little justification for the
      currently common practice of placing the haplotype together with DR1 in the group
      of DR1 haplotypes. The rearrangements in the DR haplotypes may constitute one of
      several mechanisms for increasing diversity at the DRB loci. The region of high
      instability seems to be flanked by conservatively evolving regions.

PMID- 9550404
TI  - Linkage of LMP, TAP, and RING3 with Mhc class I rather than class II genes in the
      zebrafish.
AB  - The LMP2 and LMP7 genes code for subunits of the proteasome, a multimeric
      enzymatic complex that degrades proteins into peptides. The two subunits replace
      corresponding constitutively expressed subunits during the immune response. Some
      of the peptides generated by the proteasome in the cytosol are transported by the
      products of the TAP1 and TAP2 genes into the lumen of the endoplasmic reticulum
      and are loaded onto the assembling MHC class I molecules. In mammals, the LMP2,
      LMP7, TAP1, and TAP2 genes reside in the class II region of the Mhc, closely
      linked to the RING3 gene. In the present study we identified, cloned, and
      sequenced the LMP, TAP2, and RING3 genes of the zebrafish, Danio rerio. We
      identified variants of these genes and used them in a segregation analysis of
      haploid embryos derived from heterozygous mothers. The analysis revealed that in
      zebrafish, the LMP2, LMP7, TAP12, and RING3 loci are closely linked but, in
      contrast to mammals, the LMP/TAP/RING3 cluster resides not in the Mhc class II
      but in the class I region. We also confirmed that in the zebrafish, the class I
      and class II regions are not linked to each other. In this species, therefore,
      the LMP/TAP/RING3 genes are clustered with the class I genes on a chromosome that
      apparently does not contain any class II genes. The linkage of
      LMP/TAP/RING3/class I may be the original and the LMP/TAP/RING3/class II a
      derived arrangement of these genes.

PMID- 9550405
TI  - Kappa and lambda rearrangement occur simultaneously in transformed pre-B cells.
AB  - Murine B-lineage cells can express either kappa or lambda Ig light chains.
      However, most of these cells express kappa protein, a phenomenon that appears to
      be controlled in part at the level of gene rearrangement. This feature may
      reflect a preference for the kappa locus by the recombinase machinery, or it may
      indicate that kappa rearrangement begins before lambda rearrangement. These
      possibilities can be distinguished by measuring the kinetics with which light
      chain gene rearrangement at both loci actually occurs. To this end, we have used
      pre-B cells transformed by temperature-sensitive mutants of Abelson virus that
      undergo kappa and lambda gene rearrangement when shifted to the nonpermissive
      temperature. Competitive PCR analyses of rearrangement kinetics demonstrate that
      the kappa and lambda loci rearrange at about the same time in these cells.
      Consistent with this, some clones isolated from cells induced for a short period
      of time have rearranged only the lambda locus. However, the frequency with which
      lambda genes are rearranged is three- to sixfold lower than that with which kappa
      genes rearrange. These data indicate that the recombinase machinery targets both
      light chain loci at the same time, but acts preferentially at the kappa locus.
      The reduced ability of the recombinase machinery to target the lambda locus and
      selection pressures occurring during B cell development probably both contribute
      to the preferential usage of kappa genes in normal murine B lineage cells.

PMID- 9550406
TI  - Determination of adenosine deaminase binding domain on CD26 and its
      immunoregulatory effect on T cell activation.
AB  - CD26, a 110-kDa cell surface glycoprotein, exhibits dipeptidyl peptidase IV
      enzyme activity and plays an important role in T cell costimulation. In the
      present study, we examined both the exact adenosine deaminase (ADA) binding
      domain on CD26 and the functional consequences of mutated CD26 transfectants that
      were deficient for cell surface ADA. Using CD26 deletion, human-rat swap, and
      point mutations, we found that the residues of L340, V341, A342, and R343 on the
      CD26 molecule were essential amino acids for ADA binding. When these amino acids
      were mutated and transfected into Jurkat cells, the resultant CD26 transfectants
      expressed only CD26, not ADA, on the cell surface. The amount of IL-2 produced by
      wild-type and mutated CD26 transfectants was almost the same following
      stimulation with anti-CD3 plus PMA. However, the mutated CD26 transfectants were
      much more sensitive to the inhibitory effect of adenosine on IL-2 production than
      were the wild CD26 transfectants. These data suggest that ADA on the cell surface
      does not directly involve T cell activation. Conversely, CD26 alone does not
      result in modulating the inhibitory effect of adenosine. Only the ADA bound to
      CD26 on the cell surface was functional and could counteract the inhibitory
      effect of elevated extracellular adenosine.

PMID- 9550407
TI  - Comparison of the roles of CD8 alpha alpha and CD8 alpha beta in interaction with
      MHC class I.
AB  - The CD8 molecule is expressed either as an alpha/alpha homodimer or an alpha/beta
      heterodimer on thymocytes and cytotoxic T cells, and functions as a coreceptor in
      concert with TCR for binding the MHC class I/peptide complex. Although
      CD8alpha/beta heterodimers have been shown to be more effective coreceptors, the
      precise role of the beta-chain in TCR-mediated thymic maturation and T cell
      activation is not understood. To understand the role of CD8beta in mediating
      CD8/MHC class I interaction, we examined whether cell surface CD8alpha/beta
      heterodimer promotes better cell-cell adhesion with MHC class I than the
      CD8alpha/alpha homodimer. The abilities of different forms of CD8 to adhere to
      MHC class I were measured with a cell-cell binding assay. Using a wild-type
      CD8beta and -alpha, we found that CD8alphabeta heterodimers did not mediate
      greater cell-cell adhesion than CD8alphaalpha homodimers. Furthermore, we found
      that chimeric CD8beta-alpha homodimers afforded no detectable binding. These
      results do not support the idea that CD8alphabeta binding to MHC class I is
      greater than that of CD8alphaalpha. Rather, they point to an alternative
      explanation in which CD8beta may play an role in promoting CD8/TCR interaction
      and/or in signaling/regulatory pathways.

PMID- 9550408
TI  - Influence of VH CDR3 arginine and light chain pairing on DNA reactivity of a
      bacterial DNA-induced anti-DNA antibody from a BALB/c mouse.
AB  - Anti-DNA induced in BALB/c mice by immunization with bacterial (Escherichia coli)
      DNA resemble spontaneous anti-DNA from lupus mice in V gene use and cross
      reactivity with other nuclear Ags, but lack the high V(H) CDR3 arginine content
      seen in anti-DNA from lupus mice. Moreover, the induced anti-DNA bind bacterial
      and mammalian single-stranded (ss) DNA and bacterial double-stranded (ds) DNA,
      but do not bind mammalian dsDNA. This reactivity profile is in contrast to that
      of the spontaneously arising anti-DNA of lupus mice, among which mammalian dsDNA
      reactive Abs are prominent. In this study we demonstrate that the addition of
      arginine to V(H) CDR3 of an induced anti-DNA confers the mammalian dsDNA binding
      characteristic of anti-DNA from lupus mice. The ability to confer mammalian dsDNA
      binding is dependent on both the position of the arginine in V(H) CDR3 and the
      light chain with which the heavy chain is paired, suggesting the light chain
      plays a more substantial role in DNA binding by this Ab than has previously been
      reported for other anti-DNA. Our data support the argument that V(H) CDR3
      arginines tend to confer antimammalian dsDNA reactivity, leading to censure of B
      cells expressing these Abs and provides an explanation for the absence of
      arginine-rich V(H) CDR3 in the bacterial DNA-induced response.

PMID- 9550409
TI  - Characterization of the IFN-gamma-responsive element in the 5' flanking region of
      the C1 inhibitor gene.
AB  - Treatment of a variety of cell lines with IFN-gamma leads to enhanced synthesis
      and secretion of C1 inhibitor (C1inh). The induction of C1inh synthesis by IFN
      gamma is primarily regulated at the transcriptional level, and is controlled by
      elements in the 5' flanking region and the first intron of the C1inh gene. Hep3B
      cells transfected with reporter constructs containing truncated segments between 
      738 and -81 of the 5' flanking region and stimulated with IFN-gamma expressed
      increased levels of chloramphenicol acetyl transferase. These data as well as the
      data obtained from studies using constructs with mutated IFN-gamma-activated
      sequence (GAS) indicate that the most proximal GAS element (GAS 4) that mapped to
      nucleotides -126 to -118 is responsible for this IFN-gamma responsiveness.
      Electrophoretic mobility shift assays using GAS 4 yielded a single band that
      appeared within 5 min after stimulation with IFN-gamma. In competition
      experiments, both GAS 4 and consensus GAS probes, but not a mutated GAS probe,
      competed for the GAS binding protein present in Hep3B and U-937 cell extracts.
      The identity of the GAS binding protein was confirmed using anti-STAT-1alpha Abs
      in supershift assays. The results indicate that STAT-1alpha binds to GAS 4, which
      is the primary element in the 5' flanking region responsible for IFN-gamma
      induction of the C1inh gene.

PMID- 9550410
TI  - Identification of class I genes in cartilaginous fish, the most ancient group of
      vertebrates displaying an adaptive immune response.
AB  - Sharks are members of the most primitive class of vertebrates (Chondrichthyes)
      shown to have an adaptive immune system. Suprisingly, however, class I genes have
      not been identified unambiguously in this taxon, and absence of class I loci or a
      failure to express class I genes might explain some of the relatively "weak"
      adaptive immune responses documented in cartilaginous fish. We report here the
      isolation of three unique cDNA clones from two different species of sharks that
      encode bona fide class I proteins. These clones exhibit different sequence and
      expression profiles indicating that they are likely to represent both classical
      and nonclassical class I lineages. In addition, our preliminary analysis suggests
      that there may be transfer of gene segments among shark class I genes over
      evolutionary time. The cloning of shark class I genes completes the
      identification of molecules that define the adaptive immune system (including Ig,
      TCR, and MHC class II proteins) in this taxon. Thus, simple models invoking a
      total absence of certain molecular hallmarks of the immune system to account for
      poor immune responsiveness in cartilaginous fish should be abandoned.

PMID- 9550411
TI  - A filarial nematode secreted product differentially modulates expression and
      activation of protein kinase C isoforms in B lymphocytes.
AB  - Filarial nematodes, parasitic worms that cause elephantiasis, chronic skin
      lesions, and blindness in the tropics, release a number of molecules, some of
      which appear to be immunomodulatory/suppressive, into the host environment. Here
      we demonstrate that ES-62, a phosphorylcholine-containing glycoprotein released
      by the rodent filarial parasite Acanthocheilonema viteae, interferes with
      activation of B lymphocytes by differential modulation of protein kinase C
      isoform expression. Indeed, while ES-62 selectively down-regulates expression of
      the alpha, beta, iota/lambda, delta, and zeta isoforms of PKC, it up-regulates
      expression of PKC-gamma and -epsilon in B cells. Inhibitor studies suggest that
      ES-62 appears to promote down-regulation of PKC isoforms mainly by stimulating
      proteolytic degradation. ES-62 also disrupts the normal activation and nuclear
      translocation patterns of the alpha and iota/lambda isoforms of PKC following
      ligation of the Ag receptor. The effects of ES-62 on certain PKC isoforms were
      found to be modified by coculture with IL-4. Of particular interest was the
      observation that IL-4 prevented down-regulation of PKC alpha and iota/lambda,
      isotypes considered to be active in transducing mitogenic signals.
      Phosphorylcholine-containing secreted products (phosphorylcholine-ES) are also
      released by human filarial parasites; hence we discuss how these findings may
      relate to the nature of the human B cell response during filarial infections.

PMID- 9550412
TI  - Immune responses induced by intramuscular or gene gun injection of protective
      deoxyribonucleic acid vaccines that express the circumsporozoite protein from
      Plasmodium berghei malaria parasites.
AB  - The circumsporozoite protein (CSP) is a target for effector Ab and cell mediated
      immunity against malaria parasites; DNA vaccination can induce both types of
      effector response. The immunogenicity and efficacy of two DNA plasmids expressing
      different amounts of Plasmodium berghei CSP were evaluated by immunizing BALB/c
      mice i.m. or epidermally and by varying the number of immunizations (one to three
      doses) and the interval between immunizations. Expanding the interval gave the
      strongest effect, increasing efficacy and antibody boosting, and, in the case of
      epidermal vaccination, promoting a switch in CSP-specific IgG isotypes from IgG1
      to a balance with IgG2a. The strongest humoral immune response and the greatest
      level of protection were induced by vaccinating epidermally with high expresser
      plasmid, using a gene gun to administer three doses at 6-wk intervals. For this
      group, the mean, repeat-specific, prechallenge antibody titer among mice not
      infected after challenge was significantly higher than that in infected mice, but
      the mean prechallenge titers for antibody reactive with whole sporozoites were
      not significantly different. The interval-dependent induction of IgG2a antibodies
      by epidermal vaccination contradicts the widely held belief that antibody
      responses induced by this method are restricted to those that are Th2 dependent.

PMID- 9550414
TI  - Glycoconjugates isolated from Trypanosoma cruzi but not from Leishmania species
      membranes trigger nitric oxide synthesis as well as microbicidal activity in IFN
      gamma-primed macrophages.
AB  - In the present study, we investigated the role of glycosylphosphatidylinositol
      anchored mucin-like glycoproteins (GPI-mucins) from Trypanosoma cruzi
      trypomastigotes in triggering the synthesis of nitric oxide as well as the
      microbicidal activity in murine macrophages. Our results show that GPI-mucins
      isolated from trypomastigote membranes are potent inducers of nitric oxide
      synthesis by IFN-gamma-primed macrophages, even at concentrations as low as 10
      ng/ml. Our data also indicate the important role of glycosylphosphatidylinositol
      anchors from GPI-mucins as the second signal responsible for induction of nitric
      oxide synthesis by macrophages. To further investigate the role of these parasite
      molecules in inducing parasiticidal function, we cultured macrophages in the
      presence or absence of trypomastigote GPI-mucins and/or IFN-gamma and then
      infected these cells with either Leishmania spp. or T. cruzi. IFN-gamma was
      sufficient to induce microbial activity in macrophages infected with T. cruzi
      trypomastigotes. In contrast, killing of different species of Leishmania was
      further enhanced when macrophages exposed to IFN-gamma were also costimulated
      with trypomastigote-derived GPI-mucins. Our results also indicate that different
      glycolipids obtained from Leishmania major or Leishmania donovani (i.e.,
      lipophosphoglycans or glycoinositolphospholipids) were unable to potentiate
      nitric oxide synthesis and/or microbicidal activity displayed by IFN-gamma-primed
      macrophages.

PMID- 9550413
TI  - Identification of Trypanosoma cruzi trans-sialidase family members as targets of
      protective CD8+ TC1 responses.
AB  - CD8+ T lymphocytes play a critical role in immunity to Trypanosoma cruzi.
      However, the target molecules of this T cell subset have not been elucidated. In
      this work, we report the identification of an H-2Kb-restricted CTL epitope within
      two trypomastigote surface Ags encoded by members of the T. cruzi sialidase/trans
      sialidase gene superfamily. Octapeptide VDYNFTIV sensitized target cells for
      lysis by CD8+ CTL generated from spleens of T. cruzi-infected mice. Peptide
      specific CD8+ T cell lines were cytotoxic, secreted IFN-gamma and TNF-alpha, but
      low to undetectable levels of IL-4 and IL-5, and were able, upon adoptive
      transfer, to confer a high degree of protection against challenge infection.
      Finally, the protective determinant appears to be conserved among parasites from
      diverse geographic locations. This constitutes the first identified class I MHC
      restricted epitope in T. cruzi and provides the basis for the search of
      additional targets to be considered in the development of vaccines against
      Chagas' disease.

PMID- 9550415
TI  - A secreted/shed product of Helicobacter pylori activates transcription factor
      nuclear factor-kappa B.
AB  - Helicobacter pylori is an etiologic agent in the development of chronic
      gastritis, duodenal ulceration, and gastric adenocarcinoma. Exposure of gastric
      epithelial cells to H. pylori induces secretion of the cytokine IL-8, which plays
      a pivotal role in the immunopathogenesis of H. pylori infections. Isolated
      Helicobacter strains differ in their virulence and in their ability to induce
      cytokine production. High degrees of virulence correlate with enhanced IL-8
      production. However, the molecular mechanism of this variance in Helicobacter
      pathogenicity remains poorly understood. Here we show that H. pylori-mediated IL
      8 secretion requires activation of the transcription factor nuclear factor-kappaB
      (NF-kappaB) in a gastric epithelial cell line. Several H. pylori strains which
      fail to induce IL-8 secretion do not activate NF-kappaB, while all IL-8-inducing
      strains activate the transcription factor. Moreover, the antioxidant curcumin,
      which inhibits NF-kappaB activation, also completely suppresses IL-8 induction by
      H. pylori. NF-kappaB activation is not mediated by LPSs, since purified H. pylori
      LPS had no effect on gastric epithelial cells. In contrast, both IL-8 secretion
      and NF-kappaB activation require a secreted H. pylori product, which is not
      secreted by strains mutated in picB/cagE, a recently identified putative
      transport protein.

PMID- 9550416
TI  - Depressed Langerhans cell migration and reduced contact hypersensitivity response
      in mice lacking TNF receptor p75.
AB  - Epidermal Langerhans cells (LC) belong to the dendritic cell family and represent
      the major APC within the skin. LC capture epicutaneous Ag, migrate into regional
      lymph nodes, and present Ag to T cells, thereby initiating primary immune
      response. The migratory properties of LC are an essential component of their
      function. The molecular mechanisms responsible for LC migration are far less
      defined. However, evidence has been accumulating to suggest that TNF-alpha, a
      major proinflammatory cytokine, plays an important role in promoting DC
      migration. To confirm the role of TNF-alpha in LC migration and to examine which
      type of TNF receptor signaling is involved in such an event, we utilized gene
      targeted knockout mice lacking TNF receptor p55 or p75. The migration of LC was
      assessed by examining the frequency of hapten-bearing cells in draining lymph
      nodes following hapten FITC painting, and the accumulation of dendritic cells in
      draining lymph nodes after intradermal injection of TNF-alpha. While LC migration
      was normal in p55-deficient mice, the migration was markedly depressed in p75
      deficient mice. Receptor p75-deficient mice also demonstrated a
      hyporesponsiveness in allergen-induced contact dermatitis, but a normal
      responsiveness in irritant-induced contact dermatitis. These results suggest that
      p75-dependent signaling plays a crucial role in the migration of LC and in the
      initiation of cutaneous immune responses.

PMID- 9550417
TI  - Regulation of IL-18 (IFN-gamma-inducing factor) gene expression.
AB  - IL-18 (also known as IFN-gamma-inducing factor), although structurally unrelated
      to IL-12, shares with it the role of activating NK cells and polarizing T cells
      toward Th1 cell function. To understand how the IL-18 gene (and consequently Th1
      function) is regulated, we have determined the gene structure and investigated
      the mechanisms of transcriptional control and cell type expression. The mouse IL
      18 gene comprises seven exons distributed over 26 kb. Exons 1 and 2 of this gene
      are 5'-noncoding exons. Promoter activity was detected upstream of these
      noncoding exons in two distinct regions. Both promoters are TATA-less and not G+C
      rich. The promoter activity located upstream of exon 2 was shown to act
      constitutively, while the activity located upstream of exon 1 was up-regulated in
      activated macrophage and T cell lines. IL-18 gene expression may be regulated in
      a wide range of cell types by the activities of these two distinct promoters. IL
      18 is known to be synthesized as a precursor, pro-IL-18, and its maturation is
      controlled by IL-1beta-converting enzyme (ICE). We observed concordant expression
      of IL-18 and ICE mRNAs in a wide range of cell types, unlike the more restricted
      expression of IL-12 p40 mRNA. The widespread IL-18 mRNA distribution and the
      special relationship with ICE lead us to the hypothesis that IL-18 expression may
      be coupled with apoptotic processes involving activation of ICE or ICE-like
      proteinase.

PMID- 9550418
TI  - EBV induces the production and release of IL-8 and macrophage inflammatory
      protein-1 alpha in human neutrophils.
AB  - As the first line of defense in the immune system, neutrophils may release a
      variety of potent agents upon exposure to infectious agents. In this study we
      have investigated the ability of human neutrophils to produce chemotactic
      cytokines, or chemokine in response to EBV. Exposure of neutrophils to EBV led to
      an increase in accumulation of mRNA for IL-8 and macrophage inflammatory protein
      1alpha (MIP-1alpha). EBV stimulated a time-dependent production of immunoreactive
      IL-8 and MIP-1alpha by neutrophils. The ability of EBV to stimulate the synthesis
      of IL-8 and MIP-1alpha protein was reflected by both an accumulation of the
      protein in the intracellular compartment as well as increased secretion. A
      variety of control studies support the idea that infectious EBV is not required
      for induction of chemokine gene expression; however, the response is dependent on
      the interaction between the glycoprotein gp350 of the viral envelope and the
      neutrophil surface. Since both IL-8 and MIP-1alpha are reported to be
      chemoattractants in vitro for T cells and for T and B cells, respectively, the
      ability of EBV to induce their production by neutrophils may enhance the ability
      of this virus to infect B and T lymphocytes via increased recruitment to sites of
      infection.

PMID- 9550419
TI  - Second-hand smoke is an adjuvant for T helper-2 responses in a murine model of
      allergy.
AB  - Epidemiologic studies have suggested that "second-hand smoke" increases the
      incidence and severity of allergies and asthma. To address this, we developed a
      murine model that included generation of and exposure to environmental tobacco
      smoke (ETS) followed by aerosolized Ag challenge. We report herein that exposure
      of OVA-sensitized BALB/c mice to ETS elicits a rapid and prolonged exaggerated
      response with respect to IgE, IgG1, eosinophils, and Th2 cytokines (particularly
      IL-4 and IL-10). There was a significant increase (p = 0.0159) in the total cells
      of the bronchoalveolar lavage in OVA-sensitized mice exposed to ETS when compared
      with those in ambient air. This is the first experimental data to demonstrate
      that "second-hand smoke" up-regulates the allergic response to inhaled Ag. The
      results have important health implications for children and allergic individuals
      residing in households with smokers.

PMID- 9550420
TI  - Recognition of the E-C4 element from the C4 complement gene promoter by the
      upstream stimulatory factor-1 transcription factor.
AB  - Activation of complement gene expression plays a major role in the response to
      antigenic challenge. The induction of complement synthesis occurs primarily in
      liver and in macrophages and is mediated, at least in part, by increased
      transcription of the complement genes. For example, transcription of the C4
      complement gene, which plays a crucial role in the complement pathway, is induced
      in response to acute inflammation or tissue injury. Previous work has defined the
      elements present in the C4 complement gene promoter that are required for its
      expression. Particularly important is an E-box motif, E-C4, that is conserved
      between the mouse, human, and rat promoters and that directed up to 90% of
      transcription from the mouse C4 promoter. Here we have purified the E-C4-binding
      factor to homogeneity using a novel and rapid affinity purification procedure.
      Following N-terminal microsequencing and subsequent isolation of the
      corresponding cDNA, the factor binding the E-C4 element was identified as
      upstream stimulatory factor-1 (USF-1), a basic helix-loop-helix-leucine zipper
      transcription factor. We also show for the first time that in vivo USF-1 is a
      phosphoprotein, but that phosphorylation of USF-1 is severely reduced in cells in
      culture. Moreover, the phosphorylated form of USF-1 binds DNA preferentially,
      indicating that phosphorylation may enhance the ability of USF-1 to bind DNA. The
      implications of USF-1 phosphorylation for C4 complement gene expression and
      transcription regulation are discussed.

PMID- 9550421
TI  - Cytokine induction of the ability of human monocyte CD44 to bind hyaluronan is
      mediated primarily by TNF-alpha and is inhibited by IL-4 and IL-13.
AB  - Ligation of CD44 by hyaluronan (HA) is a key proinflammatory event that regulates
      lymphocyte and monocyte adhesion and cytokine production. While most immune cells
      express CD44, few immune cells constitutively bind HA. We have previously shown
      that monocyte CD44 acquires the ability to bind HA after in vitro culture of PBMC
      in human serum and, therefore, we have investigated a series of human cytokines
      and bacterial LPS for their ability to induce and/or inhibit monocyte CD44 to
      bind HA. We found that IL-1alpha, IL-1beta, IL-3, granulocyte macrophage (GM)
      CSF, and TNF-alpha, as well as bacterial LPS, all directly induced peripheral
      blood monocytes to bind HA. In contrast, IL-2 and IL-15 up-regulated monocyte
      CD44 HA-binding in PBMC suspensions, but not in purified monocyte suspensions. An
      anti-TNF-alpha-neutralizing Ab inhibited IL-1alpha-, IL-1beta-, IL-3-, and GM-CSF
      mediated monocyte HA binding. In addition, treatment of IL-2- and IL-15
      stimulated PBMC cultures with an anti-TNF-alpha Ab prevented IL-2- and IL-15
      induced monocyte HA binding, thus identifying TNF-alpha as a lymphocyte-derived
      factor that acted on monocytes to induce HA binding. In contrast, IL-4 and IL-13
      were potent inhibitors of monocyte CD44-HA binding induced by either human serum
      or by IL-1alpha, IL-1beta, IL-3, GM-CSF, or TNF-alpha. IL-10 had dual effects on
      monocyte CD44-HA binding. Alone, IL-10 induced HA binding to PBMC monocyte CD44,
      while in contrast, IL-10 inhibited IL-1-induced monocyte CD44 binding to HA.
      Taken together, these studies identify a network of T cell and monocyte-derived
      cytokines that regulate HA binding to peripheral blood monocyte CD44, primarily
      through TNF-alpha.

PMID- 9550422
TI  - Calcium-dependent neutrophil secretion: characterization and regulation by
      annexins.
AB  - To gain direct access to the secretory machinery and study the regulation,
      mechanisms, and effectors of Ca2+-dependent neutrophil secretion, we developed an
      efficient and reproducible method of plasma membrane permeabilization using
      streptolysin O. We confirmed previous studies that permeabilized neutrophils
      secrete in response to calcium alone, but we also found that the Ca2+ dose
      response is biphasic. Secretion is detectable at <1.0 microM Ca2+ and reaches a
      plateau between 1.0 and 60 to 80 microM. When stimulated with >80 microM Ca2+,
      secretion is two- to threefold greater than at lower [Ca2+], suggesting that two
      distinct mechanisms of Ca2+-dependent secretion that differ in their affinity for
      Ca2+ exist in neutrophils. Although permeabilization allows 100% leak of lactate
      dehydrogenase, maximum secretion from permeabilized cells is 80% that of f-met
      leu-phe-stimulated intact cells, indicating that the essential components of the
      Ca2+-dependent secretory apparatus are predominantly, if not entirely, membrane
      bound. Permeabilization causes leakage of 100% of annexins V and VI, but 41% of
      annexin I and 12% of annexin III are retained. Immunofluorescence microscopy
      revealed that retained annexins I and III are associated with granule membranes.
      Addition of soluble annexins I and III to permeabilized cells increased Ca2+
      induced secretion up to 15% and 90%, respectively, implying that both annexins
      participate in this secretory pathway. While annexin V is not required for
      secretion, it inhibits the low Ca2+-affinity mechanism of secretion.

PMID- 9550423
TI  - Induction of biologically active IL-1 beta-converting enzyme and mature IL-1 beta
      in human keratinocytes by inflammatory and immunologic stimuli.
AB  - IL-1beta, a major mediator of inflammatory and immunologic skin disease,
      undergoes post-translational site-specific cleavage by a novel cysteine protease
      termed IL-1beta-converting enzyme (ICE). Although in human skin keratinocytes
      produce significant amounts of the 31-kDa IL-1beta precursor protein, they fail
      under nonpathologic conditions to convert it to the 17.5-kDa bioactive form. In
      this study, we examined whether haptens and inflammatory agents might serve as
      stimuli for ICE activity in human keratinocytes, and, if so, whether ICE activity
      might precipitate enzymatic processing of IL-1beta to its 17.5-kDa form. Baseline
      levels of ICE mRNA were detected in keratinocyte cultures devoid of Langerhans
      cells and were up-regulated by nontoxic concentrations of the reactive hapten
      urushiol and by the irritant chemicals sodium lauryl sulfate and PMA. Although
      untreated keratinocytes expressed the 31-kDa form of the protein, 17.5-kDa IL
      1beta was easily detected in keratinocytes and keratinocyte supernatants treated
      with either urushiol or the irritant chemicals. Enzymatic conversion from the 31
      kDa to the 17.5-kDa form of IL-1beta was blocked by addition of a highly specific
      aldehyde inhibitor that contained a tetrapeptide recognition sequence specific
      for ICE, but not by an aldehyde inhibitor of a related ICE-like cysteine
      protease. Induction of IL-1beta-converting enzyme by immunologic and inflammatory
      stimuli may be one of the key regulatory elements in the pathogenesis of allergic
      and irritant contact hypersensitivity.

PMID- 9550424
TI  - Extracellular ATP and UTP control the generation of reactive oxygen intermediates
      in human macrophages through the opening of a charybdotoxin-sensitive Ca2+
      dependent K+ channel.
AB  - Human monocyte-derived macrophages possess a NADPH oxidase that catalyzes
      superoxide formation upon phagocytosis. Extracellular ATP per se does not
      activate NADPH oxidase but potentiates superoxide generation triggered by
      opsonized zymosan. UTP can substitute for ATP with the same efficiency,
      suggesting that ATP mediates its effects specifically through P2U receptors.
      Extracellular UTP stimulates a rapid increase in cytoplasmic Ca2+ concentration
      in monocytic cells, which results from a release of intracellular Ca2+ stores.
      Moreover, UTP-induced calcium increase is sufficient to activate a charybdotoxin
      sensitive Ca2+-dependent outward K+ channel (K(Ca)). The activity of this channel
      develops between 0.1 and 1.0 microM free cytoplasmic Ca2+ concentration; it is
      half-blocked by 10 nM charybdotoxin but insensitive to iberiotoxin. Under
      asymmetrical K+ conditions, this K(Ca) channel does not depend on membrane
      potential and is characterized by a linear single-current voltage relationship in
      the voltage range of -100 to +50 mV, giving a unitary conductance of 10 pico
      Siemens. Interestingly, ATP/UTP-induced oxygen radicals release was inhibited by
      charybdotoxin in the same range of concentration as the UTP-induced K(Ca)
      channel. Furthermore, we show that ATP or UTP fail to enhance oxygen radicals
      production before K(Ca) channel is expressed (3 days). The electrogenic nature of
      the NADPH oxidase, i.e., its level of activation, being dependent on the plasmic
      membrane potential, might provide the causal link between the reactive oxygen
      intermediates generation and the opening of the K(Ca) channel.

PMID- 9550425
TI  - Potent induction of a neutrophil and eosinophil-rich infiltrate in vivo by human
      mast cell tryptase: selective enhancement of eosinophil recruitment by histamine.
AB  - Tryptase is the most abundant protein constituent of the secretory granules of
      human mast cells, but little is known of the contribution of this serine
      proteinase in acute allergic reactions. We have purified tryptase from human lung
      tissue by immunoaffinity procedures, and have investigated its potential to
      provoke an inflammatory infiltrate in vivo. Within 6 h of injection into the skin
      of guinea pigs, the accumulation of large numbers of neutrophils and eosinophils
      was observed, and those eosinophils closest to the injection site were partially
      degranulated. Similarly, injection of tryptase into the peritoneum of mice, even
      in quantities as low as 5 ng, stimulated the ingress of neutrophils. The response
      was dose dependent at 3, 6, and 16 h, with increases in median numbers of up to
      400-fold. At the later time points eosinophil numbers were increased by up to 10
      fold, and there were elevations also in the numbers of lymphocytes and
      macrophages. In both models, the actions of tryptase appeared to be dependent on
      an intact catalytic site. Coinjection of heparin with tryptase had relatively
      little effect on tryptase-induced responses. On the other hand, although
      histamine did not itself stimulate cell accumulation, over a range of
      concentrations it altered the cellular composition of the infiltrate induced by
      tryptase. Addition of histamine to tryptase provoked selective increases in
      eosinophil numbers of up to fivefold in the mouse peritoneum. Tryptase may
      provide an important stimulus for granulocyte recruitment in allergic disease.

PMID- 9550426
TI  - IFN-gamma and IL-10 inhibit induction of IL-1 receptor type I and type II gene
      expression by IL-4 and IL-13 in human monocytes.
AB  - The Th2-type cytokines IL-4 and IL-13 induce expression of a distinct subset of
      genes in human monocytes. These include Fc epsilonRII (CD23), 15-lipoxygenase, IL
      1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R).
      IFN-gamma has been shown to inhibit induction of CD23 and 15-lipoxygenase in
      monocytes; however, the effects of IFN-gamma on type I and type II IL-1R gene
      expression have not been defined. We examined the effects of IFN-gamma on both
      basal and IL-4/IL-13-induced IL-1R gene expression in primary monocytes. IL-4 and
      IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA
      levels. IFN-gamma decreased basal expression as well as the induction of these
      genes by IL-4 and IL-13. Inhibition of IL-1RI and IL-1RII mRNA levels by IFN
      gamma was transcriptionally mediated, and correlated directly with decreased
      production of soluble IL-1RII. Furthermore, the ability to suppress IL-1RI and IL
      1RII mRNA levels was not unique to IFN-gamma because IL-10 also inhibited
      expression of these genes in IL-4/IL-13-stimulated monocytes. Inhibition of IL-1R
      gene expression by IFN-gamma and IL-10 was not due to down-regulation of surface
      IL-4R because pretreatment with these cytokines did not decrease the number of IL
      4 binding sites per cell. However, suppression of IL-1R gene expression by IFN
      gamma and IL-10 was associated with decreased tyrosine phosphorylation and
      nuclear translocation of the IL-4/IL-13-inducible transcription factor, Stat6,
      suggesting a potential mechanism by which IFN-gamma and IL-10 may mediate their
      suppressive effects. These findings demonstrate that certain cytokines, including
      IFN-gamma and IL-10, antagonize the ability of IL-4 and IL-13 to induce increased
      expression of the IL-1RI and IL-1RII genes in monocytes.

PMID- 9550427
TI  - TNF and lymphotoxin-alpha polymorphisms associated with common variable
      immunodeficiency: role in the pathogenesis of granulomatous disease.
AB  - A subgroup of common variable immunodeficiency (CVID) patients have distinct
      clinical features, particularly granulomata splenomegaly, characteristic blood
      lymphocyte phenotype, and elevated circulating TNF levels. To investigate the
      genetic basis for this phenotype, 150 CVID patients and 200 controls were
      genotyped for six biallelic TNF and lymphotoxin-alpha (LT alpha) polymorphisms
      and eight class I and II HLA loci using PCR and sequence specific primers (PCR
      SSP) sequence-specific primers. Clinical and immunophenotypic data were collected
      for 90 patients to examine associations with CVID patient subgroups. The presence
      of granulomata (22% of patients) was strongly associated with splenomegaly, T and
      B lymphopenia, reduced CD4+ CD45RA+ T cells, and CD8+ CD57+ lymphocytosis,
      confirming the concept of a subgroup of patients with distinct clinical and
      laboratory features. The uncommon TNF +488A allele was strongly associated with
      this subgroup (p = 0.0005). The association between "granulomatous" CVID and TNF
      +488A was independent of HLA class I and II associations. We postulate that the
      presence of the TNF +488A allele, or alleles in linkage disequilibrium with it,
      contributes to the high levels of TNF and granulomatous complications
      characteristic of this subgroup of patients.

PMID- 9550428
TI  - Identification and characterization of multiple HLA-A24-restricted HIV-1 CTL
      epitopes: strong epitopes are derived from V regions of HIV-1.
AB  - HIV-1-specific CTL has a crucial role in the elimination of the virus. However, a
      restricted number of common HLA class I alleles has been studied for their
      presentation of HIV-1 CTL epitopes. We have attempted to identify HIV-1 CTL
      epitopes presented by HLA-A*2402 using reverse immunogenetics. Fifty-three HLA
      A*2402-binding HIV-1 peptides were used to induce specific CTL in PBL of four HIV
      1-infected individuals carrying HLA-A24. Twelve peptides were strongly suggested
      to be HLA-A*2402-restricted HIV-1 CTL epitopes because these peptides induced the
      specific CTL that killed both the target cells pulsed with the specific peptides
      and those infected with the vaccinia HIV-1 recombinant virus in at least one HIV
      1-infected individual. Of these epitopes, 11 were confirmed by the generation of
      the specific CTL clones. Six were the Env epitopes while three, one, and one were
      derived from Gag, Pol, and Nef proteins, respectively. Analysis of 12 HIV-1
      infected individuals using these peptides showed that 5 derived from the Env
      protein and one from the Nef protein were strong epitopes. These strong epitopes
      were derived from the diverse region of HIV-1 while weak epitopes were conserved
      in the HIV-1 clade B strain. Analysis of CTL recognition of mutations in these
      strong epitopes suggested that the mutations in the Env epitopes may critically
      influence CTL recognition in vivo.

PMID- 9550430
TI  - Diminished class II-associated Ii peptide binding to the juvenile dermatomyositis
      HLA-DQ alpha 1*0501/DQ beta 1*0301 molecule.
AB  - HLA class II molecules bind and present peptide Ags to T cells, binding specific
      sets of peptides due to polymorphism in the peptide binding groove. Class II
      proteins associate with the invariant chain (Ii chain) and its derived class II
      associated Ii peptide (CLIP). Ii chain association is important for normal
      trafficking of class II proteins to the peptide loading vesicles and for blocking
      premature access of peptides to HLA class II molecules during maturation. We have
      previously shown that juvenile dermatomyositis is associated with the HLA
      DQA1*0501 allele. There is limited information available about the interaction of
      any DQ molecule with the Ii chain and little information about binding of
      individual peptides to HLA-DQalpha1*0501/DQbeta1*0301. We sequenced peptides
      eluted from the juvenile dermatomyositis-associated class II allele HLA
      DQalpha1*0501/DQbeta1*0301. Surprisingly, we found no Ii chain or CLIP. Further
      examination of peptide binding to the HLA-DQalpha1*0501/DQbeta1*0301 molecule
      demonstrated poor CLIP binding. However, newly synthesized HLA
      DQalpha1*0501/DQbeta1*0301 molecules do associate with intact Ii chain. Molecular
      modeling suggests that CLIP binds differently to HLA-DQalpha1*0501/DQbeta1*0301
      than to DR molecules. The lack of CLIP association suggests that HLA
      DQalpha1*0501/DQbeta1*0301 has access to peptides earlier in the processing
      pathway and so might encounter novel peptides that induce autoimmunity.

PMID- 9550429
TI  - Suppression of TNF-alpha expression, inhibition of Th1 activity, and amelioration
      of collagen-induced arthritis by rolipram.
AB  - Rolipram is a type IV phosphodiesterase inhibitor that suppresses inflammation
      and TNF-alpha production. As anti-TNF-alpha therapy is effective in rheumatoid
      arthritis, we investigated the effect of rolipram on collagen-induced arthritis
      (CIA), a murine model of rheumatoid arthritis. Rolipram was administered after
      the onset of clinical arthritis at doses of 0.5, 3, 5, or 10 mg/kg twice daily,
      with a dose-dependent therapeutic effect on clinical severity and joint erosion.
      Immunohistochemical analysis of joints of rolipram-treated mice revealed 67%
      reduction in TNF-alpha-expressing cells compared with control arthritic mice. In
      vitro studies using bone marrow-derived macrophages confirmed that rolipram
      directly suppressed TNF-alpha and IL-12 production following stimulation with IFN
      gamma and LPS. The effect of rolipram on T cell activity was studied by measuring
      Th1/Th2 cytokine production by collagen-stimulated draining lymph node cells from
      arthritic mice treated in vivo with rolipram. Rolipram reduced IFN-gamma
      production and increased IL-10, indicating that rolipram down-regulated the
      ongoing Th1 response to type II collagen. Finally, the effect on CIA of
      combination therapy was studied using rolipram plus either anti-TNF-alpha or anti
      CD4 mAbs. Rolipram plus anti-TNF-alpha was not therapeutically additive, whereas
      rolipram plus anti-CD4 mAb was clearly additive. This result indicates that the
      therapeutic effects of rolipram overlap with TNF-alpha blockade, but are
      complementary to anti-CD4 treatment. It is therefore proposed that a major
      mechanism of action of rolipram in CIA is suppression of TNF-alpha activity.
      These findings suggest that type IV phosphodiesterase inhibitors may be effective
      in pathologic conditions, such as RA, with overexpression of TNF-alpha.

PMID- 9550432
TI  - A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of
      Crohn's disease.
AB  - Recent clinical studies of Crohn's disease patients demonstrated dramatic
      clinical responses following one i.v. infusion of a chimeric mAb to TNF-alpha
      (cA2). To assess the role of TNF-alpha in mucosal cytokine regulation, the
      effects of TNF-alpha on lamina propria mononuclear cell (LPMC) Th1 production
      were determined. Increased IFN-gamma production was demonstrated in anti-CD2
      stimulated LPMC cultured in TNF-alpha. To determine the effects of cA2 on
      cytokine production, TNF-alpha- and IFN-gamma-producing cells were quantitated in
      LPMC from five Crohn's disease patients treated with cA2. In all four patients
      who demonstrated clinical and endoscopic improvement, decreased numbers of LPMC
      producing IFN-gamma and TNF-alpha following CD2/CD28 activation paralleled
      improvement in disease activity over 8 wk. In one patient who did not improve,
      increased numbers of TNF-alpha- and IFN-gamma-secreting LPMC were observed. In
      three of four responding patients, CD2/CD28-activated PBMC demonstrated increased
      IFN-gamma production over 8 wk. These observations suggest that TNF-alpha may be
      a cofactor for mucosal Th1 responses, and improvement in clinical parameters and
      intestinal inflammation induced by cA2 in Crohn's disease may be mediated by down
      regulation of mucosal Th1 cytokines.

PMID- 9550431
TI  - Inhibition of inducible nitric oxide synthase intensifies injury and functional
      deterioration in autoimmune interstitial nephritis.
AB  - T lymphocytes are exquisitely sensitive to the antiproliferative effects of
      nitric oxide. We examined the effects of oral administration of two nitric oxide
      synthase inhibitors, Nw-nitro-L-arginine methyl ester (L-NAME) and L-N6-(1
      iminoethyl)lysine (L-NIL), on the course of T cell-dependent autoimmune
      interstitial nephritis in Brown Norway rats. Kidneys from rats immunized to
      produce interstitial nephritis display a net generation of nitric oxide end
      products. By immunohistochemical staining, the cytokine-inducible nitric oxide
      synthase (iNOS) is expressed in cortical tubular epithelial cells. Treatment with
      either inhibitor results in markedly more severe disease following immunization.
      Animals receiving L-NAME were hypertensive, while those treated with L-NIL, a
      highly selective inhibitor of iNOS, were not. Evaluation of the expression of IFN
      gamma, IL-2, and IL-4 in diseased kidneys by quantitative reverse transcriptase
      PCR demonstrated that L-NAME-treated animals displayed significantly augmented
      levels of IFN-gamma and IL-2 with preserved ratios of IFN-gamma/IL-4 and IL-2/IL
      4, while L-NIL-treated animals had augmented levels of IL-2 and IFN-gamma with
      augmented IFN-gamma/IL-4 and IL-2/IL-4 ratios. Animals treated with L-NAME or L
      NIL both had augmented Ag-specific IgG responses. The L-NAME group demonstrated
      increases in both the IgG2a and IgG1 subtypes, with a constant IgG2a/IgG1 ratio,
      while the L-NIL group demonstrated an increase in the ratio of the IgG2a/IgG1
      response. These Ab and cytokine data suggest that the L-NIL-treated animals had a
      skewing of their immune response toward a Th1-like response. We conclude that in
      autoimmune interstitial nephritis, generation of nitric oxide through the iNOS
      pathway has host-protective effects, and suggest that this may be broadly
      applicable to T cell-mediated pathologies.

PMID- 9550433
TI  - Association of CD4+ T cell-dependent keratitis with genetic susceptibility to
      Pseudomonas aeruginosa ocular infection.
AB  - The role of T lymphocytes in susceptibility to Pseudomonas aeruginosa corneal
      infection was studied in inbred C57Bl/6 (B6) beta2-microglobulin+/+ (beta2m+/+)
      and beta2m-/- knockout (KO) mice on a B6 genetic background. The corneas of both
      B6 and KO mice perforated by 7 days postinfection (p.i.). Histopathology revealed
      a similar inflammatory response characterized by an infiltration of
      polymorphonuclear neutrophilic leukocytes by 24 h p.i. in both groups of mice.
      CD4+ and CD8+ (latter absent in KO) T cells were present in cornea by 3 days
      p.i., and by 5 days, IL-2R-positive cells were positively immunostained. Corneas
      of B6 beta2m+/+ mice depleted of CD4+ T cells and infected with P. aeruginosa did
      not perforate at 7 days p.i. vs mice depleted of CD8+ T cells or treated with an
      irrelevant mAb. Neutralization of IFN-gamma before infecting B6 mice prevented
      corneal perforation and was associated with a lower delayed-type hypersensitivity
      than in B6 mice similarly treated with an irrelevant mAb. These data provide
      evidence that a CD4+ T cell (Th1)-dominated response following P. aeruginosa
      corneal infection is associated with genetic susceptibility and corneal
      perforation in inbred B6 mice.

PMID- 9550434
TI  - Demonstration and functional analysis of IL-10 receptors in human epidermal
      cells: decreased expression in psoriatic skin, down-modulation by IL-8, and up
      regulation by an antipsoriatic glucocorticosteroid in normal cultured
      keratinocytes.
AB  - The chronic skin disease psoriasis is characterized by epidermal
      hyperproliferation and inflammation. The exact etiology of the disease is still
      unknown. At the molecular level, overexpression of growth factors and
      proinflammatory cytokines such as IL-8 and the corresponding receptor has been
      described in psoriatic plaques. On the other hand, the loss of inhibitory control
      mechanisms is involved in the pathogenesis of the disease, as exemplified by the
      reduced mRNA levels for the cell cycle inhibitor p53 found in lesional skin. Here
      we extend these findings to a cytokine with negative regulatory functions, IL-10.
      Only under certain conditions are human keratinocytes able to synthesize IL-10.
      In skin, pathological overexpression of IL-10 was described om atopic dermatitis.
      IL-10 exerts its effects via a specific receptor (IL-10R). We show here for the
      first time the presence and functionality of IL-10R in epidermal cells and its
      dramatically decreased expression in acute exanthematic psoriatic epidermis by in
      vitro and in situ binding studies. These results were substantiated using
      semiquantitative reverse transcriptase-PCR, demonstrating decreased expression of
      the IL-10R gene in psoriatic skin, its down-modulation by the proinflammatory
      cytokine IL-8, and its pharmacological induction in cultured cells. Biological
      responsiveness of epidermal cells toward IL-10 could also be demonstrated by a
      reduction of the growth rate and inhibition of IFN-gamma-induced HLA-DR
      expression. Our results provide the first evidence for a role of the IL-10R gene
      in the homeostasis of the epidermis and substantiate the concept of a loss of
      negative regulatory peptides as a step in the eruption of psoriasis.

PMID- 9550435
TI  - TNF-alpha down-regulates type 1 cytokines and prolongs survival of syngeneic
      islet grafts in nonobese diabetic mice.
AB  - Administration of TNF-alpha to autoimmune diabetes-prone nonobese diabetic mice
      and biobreeding rats inhibits diabetes development; however, the mechanism(s) of
      diabetes prevention by TNF-alpha has not been established. We used the model of
      syngeneic islet transplantation into diabetic nonobese diabetic mice to study the
      effects of TNF-alpha administration on the types of mononuclear cells and
      cytokines expressed in the islet grafts and on autoimmune diabetes recurrence.
      Twice daily i.p. injections of TNF-alpha (20 microg/day) from day 1 to day 30
      after islet transplantation significantly prolonged islet graft survival; thus,
      70% (16 of 23) of mice treated with TNF-alpha were normoglycemic at 30 days after
      islet transplantation compared with none (0 of 14) of vehicle-treated control
      mice. Islet grafts and spleens from TNF-alpha-treated mice at 10 days after islet
      transplantation contained significantly fewer CD4+ and CD8+ T cells, and
      significantly decreased mRNA levels of type 1 cytokines (IFN-gamma, IL-2, and TNF
      beta) than islet grafts and spleens from control mice. Regarding type 2
      cytokines, IL-4 mRNA levels were not changed significantly in islet grafts or
      spleens of TNF-alpha-treated mice, whereas IL-10 mRNA levels were decreased
      significantly in islet grafts of TNF-alpha-treated mice and not significantly
      changed in spleens. TGF-beta mRNA levels in islet grafts and spleens were similar
      in TNF-alpha-treated and control mice. These results suggest that TNF-alpha
      partially protects beta cells in syngeneic islet grafts from recurrent autoimmune
      destruction by reducing CD4+ and CD8+ T cells and down-regulating type 1
      cytokines, both systemically and locally in the islet graft.

PMID- 9550436
TI  - Autonomic innervation of the human middle ear: an immunohistochemical study.
AB  - PURPOSE: Although there have been numerous studies of autonomic innervation of
      the middle ear mucosa, and the mechanism of effusion into the middle ear cavity
      in animals, the autonomic innervation of the human middle ear has not received
      much attention. The purpose of this study is to show the presence of
      catecholaminergic nerve fibers in the human middle-ear mucus membrane that may
      play an important role in the pathogenesis of middle-ear effusion. MATERIALS AND
      METHODS: A total of 126 celloidin-embedded temporal bone sections from the
      temporal bone bank at the House Ear Institute were used for immunohistochemical
      study. A polyclonal antibody to tyrosine hydroxylase enzyme was used to show the
      presence of catecholaminergic nerve fibers. RESULTS: Tyrosine hydroxylase
      immunoreactive nerve fibers containing numerous fine varicosities along their
      course, characteristic of noradrenergic neurons, were observed throughout the
      middle-ear mucosa including the promontary, sinus tympani, mesotympanum, and
      hypotympanum. In addition, these nerve fibers were seen in close promixity to the
      small-caliber blood vessels. A striking variation in the intensity of staining as
      well as in the amount of nerve fibers was observed among the temporal bone
      sections. CONCLUSION: It is possible that the catecholaminergic nerve fibers,
      like elsewhere in the body, may exert a direct influence on the middle-ear
      mucosal blood vessels. We speculate that the effusion into the middle-ear space
      is an active, rather than a passive process. It is conceivable that cholinergic
      sympathetic nerves might exist in the human middle-ear mucus membrane, and that
      these autonomic nerves, in conjunction with the neuropeptides, may play an active
      role in the pathogenesis of human middle-ear effusion.

PMID- 9550437
TI  - Prognostic significance of vascular and perineural invasion in cancer of the
      larynx.
AB  - PURPOSE: Perineural and vascular invasion are generally recognized as poor
      prognostic factors in cancer. The authors report the prognostic significance of
      perineural and vascular invasion in cancer of the larynx. MATERIALS AND METHODS:
      The laryngectomy specimens of 94 patients with squamous cell carcinoma of the
      larynx were analyzed histopathologically for vascular and perineural invasion.
      Prognostic significance of vascular and perineural invasion was evaluated related
      to the cervical lymph node metastasis, recurrence, and disease-free survival.
      RESULTS: Vascular invasion significantly influences cervical lymph node
      metastasis for supraglottic tumors, yet not for glottic and transglottic tumors.
      Perineural invasion has marginal significance in cases of cervical lymph node
      metastasis of supraglottic tumors; it has no significance in cases of cervical
      lymph node metastasis of glottic and transglottic tumors. Vascular invasion
      significantly increases local and regional recurrence rate, but not distant
      metastasis rate. Perineural invasion significantly increases local recurrence
      rate, but not regional recurrence and distant metastasis rate. The disease-free
      survival is significantly shortened by the presence of vascular and perineural
      invasion. According to multivariant analysis, neither vascular nor perineural
      invasion significantly effects the disease-free survival independently (P> .15).
      The presence of vascular invasion significantly affects the recurrence
      independently (P=.045). The presence of vascular invasion significantly reduces
      the interval between surgery and the development of recurrence (P=.013).
      CONCLUSION: The presence of vascular and perineural invasion should be checked in
      every laryngectomy specimen because both have a significant prognostic value;
      both influence the disease-free survival and recurrence significantly. Vascular
      invasion significantly increase cervical lymph node metastasis of supraglottic
      tumors; perineural invasion has only marginally significant effect on cervical
      lymph node metastasis of supraglottic cancers. Vascular invasion plays an
      independent role in determining the recurrence.

PMID- 9550438
TI  - Donor site evaluation for fibula free flap transfer.
AB  - PURPOSE: The role of routine preoperative angiography in patients undergoing
      fibula flap transfer remains controversial. A recent survey of experienced
      microvascular surgeons indicated that routine angiography may be unnecessary in
      patients with no symptoms of peripheral vascular disease and normal lower
      extremity pulses. To study the necessity of performing preoperative vascular
      imaging studies, the incidence of congenital and acquired vascular anomalies that
      prevented the harvest of a fibula flap is reported in a series of patients
      undergoing evaluation for oromandibular reconstruction PATIENTS AND METHODS: A
      series of 19 consecutive patients who underwent preoperative lower extremity
      vascular imaging studies in anticipation of performing a fibula free flap is
      presented. RESULTS: Angiographic findings significantly altered the surgical
      reconstruction that was performed in 4 of 19 (21%) patients. Three patients with
      a history or examination suggestive of peripheral vascular disease were excluded
      on the basis of the findings at the time of radiographic study. In a fourth
      patient, the contralateral leg was used for reconstruction when preoperative
      angiography showed a dominant peroneal artery supplying the foot in the extremity
      initially considered for flap harvest. CONCLUSION: History and physical
      examination are not helpful in detecting most congenital vascular anomalies that
      would place the foot at risk for ischemia if the peroneal artery is sacrificed.
      The findings of this small series are consistent with the previously documented
      incidence of anomalous blood supply to the foot and demonstrate the need for
      preoperative vascular imaging studies in patients undergoing fibula free flap
      transfer to avoid a potentially catastrophic complication.

PMID- 9550439
TI  - The pectoralis major myofascial flap: clinical applications in head and neck
      reconstruction.
AB  - PURPOSE: The pectoralis major myofascial (PMMF) flap, a simple variant of the
      pectoralis major myocutaneous (PMMC) flap, has been underemphasized as a
      reconstructive method in head and neck surgery. MATERIALS AND METHODS: In the
      present study, we review our experience using 18 PMMF flaps for a variety of
      reconstructive purposes in 15 head and neck cancer patients treated at a tertiary
      care hospital. Twelve of the study patients were undergoing surgical salvage of a
      recurrent cancer, and 10 had received previous radiation. RESULTS: The overall
      rate of flap complications in our series was 22%, and the incidence of major flap
      complications requiring surgical revision was 11%. CONCLUSION: In our experience,
      the use of the PMMF flap for a variety of reconstructive tasks in the head and
      neck has been associated with a high overall success rate with avoidance of some
      of the limitations of the PMMC flap.

PMID- 9550440
TI  - Facial nerve function after cerebellopontine angle surgery and prognostic value
      of intraoperative facial nerve monitoring: a critical evaluation.
AB  - PURPOSE: Facial nerve monitoring is often used to predict postoperative facial
      function after acoustic neuroma tumor removal. In this study, three methods of
      predicting facial nerve function were compared. These methods used various
      parameters of the evoked electromyographic monitoring. MATERIALS AND METHODS:
      Thirty-four patients who underwent surgery for acoustic neuroma were
      retrospectively reviewed. Amplitude of ongoing electromyographic activity,
      stimulation current thresholds, and the amplitude of evoked response were
      analyzed. The predictive value of the three methods was compared with actual
      postoperative facial nerve function. RESULTS: One method predicted the final
      postoperative facial function in 90% of the patients, one method in 84%, and the
      final method failed to predict the final VIIth nerve function in patients with
      current stimulation thresholds greater than 0.05 mA. CONCLUSION: Analysis of
      prognostic value showed that one of the three studied proved superior in
      predicting facial nerve function.

PMID- 9550441
TI  - Globus sensation after laser-assisted uvulopalatoplasty.
AB  - PURPOSE: To determine the cause of globus sensation following laser-assisted
      uvulopalatoplasty (LAUP). MATERIALS AND METHODS: Sixty consecutive LAUP patients
      were questioned regarding globus sensation. Palate sensation on globus patients
      was mapped and compared with asymptomatic LAUP control patients. Symptomatic
      patients were tested again 2 months later. RESULTS: There was a 25% incidence of
      globus with 8% rated severe and 16% rated mild. The globus sensation corresponds
      to an insensate area of palate (P < .01). Resolution of the symptoms coincides
      with reemergence of sensation on the palate. CONCLUSION: Sensory dennervation of
      the central palate is a likely source of post-LAUP globus sensation. As sensation
      returns, symptoms abate. Palate surgery should be designed with this in mind. It
      is possible that undiagnosed globus patients may have areas of anesthetic
      pharynx.

PMID- 9550442
TI  - Significance of trisomy 7 related to PCNA index in cholesteatoma.
AB  - PURPOSE: To define the biological features of the variable aggressiveness of
      cholesteatoma, we performed a retrospective cytogenetic and kinetic study.
      MATERIALS AND METHODS: We studied 44 cases of cholesteatoma by using fluorescence
      in situ hybridization with specific alpha-satellite DNA probes for chromosome 7
      and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA)
      with PC10 monoclonal antibody. RESULTS: We observed the presence of three or four
      chromosome 7 in elevated percentages of cells of 23 cases, and a high PCNA index
      (above mean value) in 22 cases. CONCLUSION: Based on our results, we maintain
      that the presence of an extra chromosome 7 is correlated with an increase of
      proliferative activity. Therefore, trisomy 7 can be considered a prognostic
      marker and an indicator of aggressive behavior in cholesteatoma.

PMID- 9550443
TI  - Parathyroid preservation during thyroid surgery.
AB  - PURPOSE: Even though thyroid surgery is generally quite safe, permanent
      hypoparathyroidism is a very distressing complication. The incidence of
      hypoparathyroidism is directly proportional to the extent of thyroidectomy, and
      inversely proportional to the experience of the surgeon. It is also related to
      the extent of invasion of thyroid cancer and of the degree of dissection in the
      tracheo-esophageal groove. The incidence reported in the literature varies
      between 1% to 29%. Total thyroidectomy results in a higher incidence of
      hypoparathyroidism. MATERIALS AND METHODS: This report describes experiences with
      600 thyroidectomies over a period of 11 years. The major indications for surgery
      included suspicion or proof of malignancy, compression symptoms, and substernal
      goiters. Twenty-six patients underwent surgery for Graves' disease. There were
      221 men and 379 women, ranging in age from 16 to 89 years; 88% of the patients
      had benign disease, whereas 12% of the patients had malignant pathology. The
      surgical procedures included 62 total thyroidecotmies, 188 subtotal
      thyroidectomies, and lobectomy and isthmectomy in 350 patients. RESULTS:
      Meticulous tracheo-esophageal groove dissection, identification of parathyroids
      and their preservation, including the blood supply, was routine in each case.
      Even in patients undergoing unilateral lobectomy, every effort was made to
      preserve the parathyroids. If any of the parathyroids or its blood supply was
      injured, it was autotransplanted in the sternomastoid muscle. Only two patients
      developed temporary hypoparathyroidism. CONCLUSION: Parathyroid
      autotransplantation is performed whenever one or more of the parathyroids are
      damaged. Parathyroid preservation during thyroid surgery is crucial in the
      overall management of thyroid diseases.

PMID- 9550444
TI  - Supraglottic laryngectomy.

PMID- 9550445
TI  - Nasal tooth.

PMID- 9550446
TI  - Vascular leiomyoma of the carotid sheath simulating a carotid body tumor.

PMID- 9550447
TI  - Computer coregistration of positron emission tomography and magnetic resonance
      images in head and neck cancer.
AB  - PURPOSE: Early experience has shown that positron-emission tomography (PET) is a
      useful technique for the detection of occult squamous cell carcinoma of the head
      and neck. Although highly sensitive, PET lacks definition of anatomic detail and
      therefore does not localize pathology precisely. To circumvent this limitation, a
      computerized coregistration technique has been developed at the University of
      California-Los Angeles to correlate PET and magnetic resonance images (MRI). This
      method allows accurate, precise anatomic localization of areas of heightened
      glucose metabolism, including subclinical tumors. MATERIALS AND METHODS: The
      technique uses a coregistration computer program that precisely superimposes the
      PET scan with the corresponding MRI image. RESULTS: Two cases are presented in
      which PET-MRI coregistration was used to anatomically define the areas of
      heightened glucose metabolism. Large tumors were selected because the precision
      of the method can be verified. CONCLUSION: The coregistration technique is a
      valuable addition to PET imaging, particularly in its ability to anatomically
      localize PET findings. The most important application of this technique is to
      facilitate the biopsy of subclinical lesions identified on PET.

PMID- 9550448
TI  - Lingual thyroid: endoscopic management with CO2 laser.

PMID- 9550449
TI  - Bilateral parotid gland metastases as the initial manifestation of a small cell
      carcinoma of the lung.

PMID- 9550450
TI  - The insulin system: influence of antioxidants.

PMID- 9550451
TI  - Nutrition and physical activity with particular emphasis on bone health.

PMID- 9550452
TI  - The glucose/insulin system and vitamin C: implications in insulin-dependent
      diabetes mellitus.
AB  - The cellular uptake of vitamin C (ascorbic acid, ASC) is promoted by insulin and
      inhibited by hyperglycemia. If a rise in plasma ASC is uncoupled from insulin
      replacement in insulin-dependent diabetes mellitus (IDDM) then the degree of
      hyperglycemia could account for "tissue scurvy" in IDDM. Leukocyte ASC is lower
      in IDDMs compared with nondiabetics when vitamin C consumption is adequate and
      our data suggest that this is a variable component of the pathophysiology of
      IDDM. The complications of diabetes mellitus are believed to result from either
      the intracellular accumulation of sorbitol or the nonenzymatic glycoxidation of
      proteins or both. With respect to the abnormal cellular accumulation of sorbitol,
      vitamin C supplementation has been shown to be effective in several studies of
      adults with diabetes; the situation regarding the prevention of protein
      glycoxidations by supplementation is presently unclear. The roles of ASC as an
      aldose reductase inhibitor and a water soluble antioxidant in body fluids are
      potentially very important as adjuncts to tight glycemic control in the
      management of diabetes. Tissue saturation and maximal physiologic function in
      IDDM may require supplemental vitamin C intake.

PMID- 9550453
TI  - Zinc, insulin and diabetes.
AB  - The relationship between diabetes, insulin and zinc (Zn) is complex with no clear
      cause and effect relationships. In Type 1 diabetes there is a lack of insulin
      production, in Type 2 diabetes resistance to the effects of insulin are
      predominant. Both Type 1 and Type 2 have the same long-term complications.
      Diabetes effects zinc homeostasis in many ways, although it is most probably the
      hyperglycemia, rather than any primary lesion related to diabetes, which is
      responsible for the increased urinary loss and decreases in total body zinc. The
      role of Zn deficiency, which could, at least potentially, exacerbate the cytokine
      induced damage in the autoimmune attack which destroys the islet cell in Type 1
      diabetes, is unclear. Since Zn plays a clear role in the synthesis, storage and
      secretion of insulin as well as conformational integrity of insulin in the
      hexameric form, the decreased Zn, which affects the ability of the islet cell to
      produce and secrete insulin, might then compound the problem, particularly in
      Type 2 diabetes. Several of the complications of diabetes may be related to
      increased intracellular oxidants and free radicals associated with decreases in
      intracellular Zn and in Zn dependent antioxidant enzymes. There appears to be a
      complex interrelationship between Zn and both Type 1 and Type 2 diabetes. The
      role of Zn in the clinical management of diabetes, its complications, or in its
      prevention is, at best, unclear.

PMID- 9550454
TI  - Comparative effects of chromium, vanadium and gymnema sylvestre on sugar-induced
      blood pressure elevations in SHR.
AB  - OBJECTIVE: Effects on systolic blood pressure (SBP) of ingesting three agents
      reported to influence insulin metabolism, i.e., chromium polynicotinate,
      bis(maltolato)oxovanadium (BMOV), and the herb, Gymnema sylvestre, were assessed
      simultaneously in spontaneously hypertensive rats (SHR). METHODS: In the first
      study, SHR were fed either a starch, sugar, or sugar diet containing chromium
      polynicotinate, bis(maltolato)oxovanadium (BMOV), or G. sylvestre. Tail SBP was
      estimated indirectly and various blood chemistries were measured. TBARS formation
      was determined in hepatic and renal tissue. In a second study, tail SBP was
      measured in SHR ingesting diets containing different concentrations of BMOV.
      RESULTS: Compared to starch, SHR consuming sucrose showed a significant elevation
      of SBP within days that was maintained for the duration of study. Addition of
      chromium polynicotinate to the sucrose diet at the beginning of study prevented
      the sucrose-induced elevation of SBP for 2 weeks, but SBP rose significantly
      after that. BMOV at high concentrations overcame the sucrose-induced rise in SBP
      and even decreased SBP below values seen in SHR eating the starch diet, but
      marked weight loss was noted. A second study examined different concentrations of
      BMOV. At 0.01% w/w concentration of BMOV, SBP was still significantly decreased,
      even though SHR did not lose body weight (BW) early on. SHR consuming G.
      sylvestre showed no change or even elevated SBP. Hepatic thiobarbituric acid
      reacting substances (TBARS) formation, an estimate of lipid peroxidation, was
      decreased by chromium polynicotinate and BMOV, and renal TBARS by chromium
      polynicotinate. Circulating cholesterol concentrations were decreased in the SHR
      consuming G. sylvestre. CONCLUSIONS: Chromium decreases the portion of SBP
      elevated by high sucrose intake as shown previously, but high levels of sucrose
      ingestion can eventually overcome this. BMOV overcame sucrose-induced elevation
      of SBP as well as some of the "genetic hypertension." Different from chromium,
      this decrease was not overcome by high levels of dietary sucrose. The significant
      lowering of cholesterol with G. sylvestre ingestion indicates some effect on
      metabolism, but G. sylvestre did not lower and even raised SBP.

PMID- 9550455
TI  - The effect of a marathon run on plasma and urine mineral and metal
      concentrations.
AB  - BACKGROUND: Little data exist on the requirements of trace metals and minerals
      for endurance athletes. Changes in body status of these elements must be examined
      before specific nutritional recommendations can be made. This study was designed
      to determine whether a marathon run was associated with changes in serum and
      urine metal and mineral concentrations. METHODS: Forty subjects who planned to
      complete the 1996 Houston-Tennaco marathon were recruited. Subjects had blood and
      urine samples collected 2 weeks prior to the race and immediately following the
      race. Blood and urine specimens were analyzed for copper, iron, magnesium and
      zinc concentrations. Blood was also analyzed for calcium concentration and
      ceruloplasmin activity. RESULTS: Twenty-six subjects (24 male, 2 female)
      completed the marathon. Finish times varied between 2 hours 43 minutes and 5
      hours 28 minutes. There was no significant change in serum calcium, copper or
      zinc concentrations or ceruloplasmin activity. Serum and urine magnesium
      concentration decreased significantly (19.55+/-1.73 to 16.55+/-1.53 ppm,
      p=0.00001; 34.02+/-8.64 to 21.80+/-12.24 ppm, p=0.003, respectively). Serum iron
      concentration increased significantly (1.06+/-0.48 to 1.35+/-0.42 ppm, p=0.006),
      while urine copper and iron concentrations were below the limits of detection,
      zinc concentration did not change. CONCLUSIONS: Serum and urinary magnesium
      concentrations decrease during endurance running, consistent with the possibility
      of magnesium deficiency. This may be related to increased demand in skeletal
      muscle. Serum iron concentration increases, possibly related to tissue injury.
      The exact etiology for these observations, as well as their clinical
      significance, requires further investigation.

PMID- 9550456
TI  - Stress fractures in female army recruits: implications of bone density, calcium
      intake, and exercise.
AB  - OBJECTIVE: To identify characteristics and factors associated with increased risk
      for stress fractures in military women. DESIGN: Case-control study to
      retrospectively examine physical activity, prior calcium intake, and bone density
      as predictors of stress fractures. SETTING: A military training installation
      which incorporates physical training for women. SUBJECTS: Forty-nine female
      soldiers with confirmed stress fractures (cases) and 78 female soldiers with no
      orthopedic injuries (controls), aged 18 to 33 years. MEASURES: Retrospective self
      reports of habitual exercise, sports participation, and food intake; current
      height, weight, and body mass index (BMI); demographic variables (age, ethnicity,
      menstrual patterns, smoking habits); and bone density on radiologically defined
      stress fractures. RESULTS: Cases and controls were similar in height, weight, and
      BMI. Measurements of bone density (g/cm2) at the trochanter (cases, 0.77+/-0.09;
      controls, 0.77+/-0.08); femoral neck (cases, 0.94+/-0.10; controls, 0.94+/-0.09);
      Ward's triangle (cases, 0.91+/-0.11; controls, 0.93+/-0.11); lumbar spine (cases,
      1.21+/-0.12; controls, 1.24+/-0.10); and radius shaft (cases, 0.67+/-0.09;
      controls, 0.68+/-0.05) were not different between groups. Calcium intake was not
      different between groups (cases, 1154+/-751 mg/day; controls, 944+/-513 mg/day)
      and did not correlate with bone density (r=0.01 to -0.06 at four sites). Sports
      participation positively correlated with bone density in the hip (r=0.49).
      Leisure activity energy expenditure (kcal/day) tended toward association with
      lower stress fracture risk as expenditure level increased (p=0.06). CONCLUSION:
      Stress fracture in female Army recruits was not correlated with bone density or
      calcium intake during adolescence, although a weak relationship to prior physical
      activity was observed.

PMID- 9550457
TI  - Relation of nutrition, body composition and physical activity to skeletal
      development: a cross-sectional study in preadolescent females.
AB  - OBJECTIVE: To examine the relation of anthropometric and growth parameters
      (weight, stature, body composition, age, and skeletal age), nutritional factors,
      and physical activity to the total body and radius bone mineral density and
      content and radiogrammetry parameters of the second metacarpal. STUDY DESIGN: The
      study was a cross-sectional evaluation of 456 healthy, Caucasian girls, ages 8 to
      13 years. Multiple regression models were created based on Cp statistics to
      determine the association between bone parameters and various independent
      variables. RESULTS: Mean calcium intake was 956+/-381 mg/day, about 20% below the
      RDA of 1200 mg/day and about 36% below the threshold intake of approximately 1500
      mg/day. The most significant predictors for total body and radius bone mineral
      density were corresponding bone areas, lean body mass, body fat, skeletal age,
      dietary calcium, and stature (only for total body) with corresponding
      R2(adjusted) of 48% and 36%. The total body and radius bone mineral content was
      positively associated with corresponding bone areas, lean body mass, body fat,
      calcium intake, and skeletal age with corresponding R2(adjusted) of 86% and 72%.
      Energy expenditure (corrected for BMI) was stratified into quartiles and bone
      mass parameters were distributed accordingly. A statistically significant
      difference in total body and radius bone mineral density and content was noted
      between the fourth and lower quartiles (ANOVA, p<0.05 to p<0.0001). CONCLUSION:
      The most significant predictors of bone mass in preadolescent females evaluated
      in this study are bone area, lean body mass, body fat, skeletal age and dietary
      calcium.

PMID- 9550458
TI  - Calciuric effects of short-term dietary loading of protein, sodium chloride and
      potassium citrate in prepubescent girls.
AB  - OBJECTIVE: Studies using adult human subjects indicate that dietary protein and
      sodium chloride have negative effects on the retention of calcium by increasing
      urinary calcium excretion, while alkaline potassium improves calcium retention
      along with decreasing urinary calcium losses. This study investigated the effect
      of these dietary factors on acute urinary calcium excretion in 14 prepubescent
      girls age 6.7 to 10.0 years. METHODS: Subjects provided a fasting urine sample
      then consumed a meal containing one of five treatments: moderate protein (MP)
      providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na),
      high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium
      chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate
      (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental
      protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and
      unless intentionally altered, components of interest except phosphate were equal
      between treatments. Each subject completed all five treatments. RESULTS: Urinary
      calcium excretion rose after the meal, peaking at 1.5 hours. There were no
      significant differences in calcium excretion between treatments at any time
      point. The high protein treatments did not result in a significant increase in
      either net acid or sulfate excretion at 1.5 hours compared to moderate protein.
      Dietary sodium chloride had no effect on urinary sodium or calcium excretion over
      the 3 hours. After the potassium treatment, sodium excretion increased (p< or
      =0.002) and net acid excretion decreased (p<0.001) compared to other treatments
      at 1.5 hours. CONCLUSIONS: In children, a simultaneous increase in protein and
      phosphorus due to increased milk protein intake did not increase acute urinary
      calcium excretion. An effect of dietary sodium chloride on acute urinary calcium
      excretion was not observed. Both these findings were similar to those of adult
      studies previously conducted in the same laboratory using similar format and
      treatments. Potassium citrate was not hypocalciuric in children, a response
      differing from that for adults, who have shown a decrease in acute urinary
      calcium excretion in response to alkaline potassium treatment. Further
      characterization of calciuric responses to dietary factors is required for
      children, who may differ from adults in many respects.

PMID- 9550459
TI  - Nightly enteral nutrition support of elderly hip fracture patients: a phase I
      trial.
AB  - OBJECTIVE: This non-blinded randomized controlled trial was the first phase of a
      planned series of investigations designed to test the efficacy of aggressive post
      operative enteral nutrition support to decrease the rate of post-operative
      complications or improve long-term outcomes in specifically defined subgroups of
      elderly patients who have sustained a hip fracture requiring surgery. METHODS:
      Eighteen patients (17 males) were randomized to the treatment (eight male
      subjects) or control groups. The control group (mean age 76.5+/-6.1 years)
      received standard post-operative care. Subjects in the treatment group (mean age
      74.5+/-2.1 years) received 125 cc/hour of nasoenteral tube feedings over 11 hours
      each night in addition to standard post-operative nutritional care. RESULTS: Both
      the treatment and control groups had reduced volitional nutrient intakes for the
      first 7 post-operative days (3,966+/-2,238 vs. 4,263+/-2,916 kJ/day [948+/-535
      vs. 1019+/-697 kcal/day], p=0.815), but the treatment subjects had a greater
      total nutrient intake (7,719+/-2,109 vs. 4,301+/-2,858 kJ/day [1845+/-504 vs.
      1028+/-683 kcal], p=0.012). On average, treatment subjects were tube fed for
      15.8+/-16.4 days. There was no difference between the groups (treatment vs.
      controls) in the rate of post-operative life-threatening complications (25 vs.
      30%, p=1.00) or in-hospital mortality (0 vs. 30%, p=0.216). Mortality within 6
      months subsequent to surgery was lower in the treatment group compared to the
      controls (0 vs. 50%, p=0.036). DISCUSSION: We conclude that nightly enteral
      feedings are a safe and effective means of supplementing nutrient intake. The
      greatest impact of nutrition support may be to reduce mortality.

PMID- 9550460
TI  - Plasma vitamins E and C concentrations of adult patients during cardiopulmonary
      bypass.
AB  - OBJECTIVE: This study was designed with two aims: 1) to determine if the coronary
      artery bypass graft (CABG) procedure alters plasma vitamin E and C concentrations
      of adult patients through repeated determinations of vitamin levels at time
      points before, during and following CABG, and 2) to assess whether plasma vitamin
      E concentrations reflect myocardial tissue content. METHODS: A consecutive sample
      of 38 patients undergoing CABG surgery at a Midwest tertiary care hospital was
      enrolled. Patients receiving blood transfusions before or during surgery were
      excluded. RESULTS: Plasma vitamin E/total lipid ratios rose with reperfusion,
      remained elevated immediately following bypass, and fell to preoperative
      concentrations by 24 hours. Plasma vitamin E/total cholesterol levels varied
      little throughout this time course. Both plasma uric acid and ascorbate
      concentrations (corrected for hemodilution) also rose by the preischemic
      interval, and remained elevated until a return to preoperative levels by 24
      hours. Corrected malondialdehyde (MDA) concentrations rose by pre-ischemia but
      returned more quickly to preoperative levels. Atrial appendage tissue vitamin E
      concentrations bore a significant relationship to those of plasma prior to
      surgery (r=+0.49, p=0.004). Reported supplement use, plasma concentrations and
      body mass index contributed to the variability in atrial tissue concentrations of
      vitamin E. CONCLUSIONS: In short, when not confounded by transfusions or
      hemodilution, several peripheral indices of antioxidants increase with the
      reperfusion segment of CABG procedure and return to baseline levels within 24
      hours of surgery. Parallel changes in MDA were observed. The observed changes are
      consistent with the hypothesis that oxidative stress accompanies the ischemia
      reperfusion components of the CABG procedure.

PMID- 9550461
TI  - Oxidative changes associated with beta-carotene and alpha-tocopherol enrichment
      of human low-density lipoproteins.
AB  - OBJECTIVE: To determine what effects enrichment of human low-density lipoprotein
      (LDL) with combinations of alpha-tocopherol and beta-carotene would exert on LDL
      oxidation and attempt to define the nature of the effects. METHODS: Human plasma
      was pooled and alpha-tocopherol and beta-carotene was added in a four-by-four
      design resulting in the enrichment of LDL with alpha-tocopherol and beta-carotene
      in varying concentrations. Enriched and control LDL was oxidized in Cu2+ mediated
      oxidation system and resistance of LDL to oxidation was determined by lag time,
      thiobarbituric acid reactive substances (TBARS) activity, and rate of oxidation.
      RESULTS: Increasing LDL alpha-tocopherol concentration had a linear relationship
      with lag time and a negative correlation with rate of oxidation. LDL beta
      carotene concentration was linearly correlated with the rate of LDL oxidation and
      beta-carotene loss, and exponentially related to TBARS concentration.
      CONCLUSIONS: These results support earlier findings for the protective effect of
      a-tocopherol against LDL oxidation, and suggest that beta-carotene participates
      as a prooxidant in the oxidative degradation of LDL under these conditions. Since
      high levels of alpha-tocopherol did not mitigate the prooxidative effect of beta
      carotene, these result indicate that increased LDL beta-carotene may cancel the
      protective qualities of alpha-tocopherol.

PMID- 9550462
TI  - The phenomenon of "picky eater": a behavioral marker in eating patterns of
      toddlers.
AB  - OBJECTIVE: To determine if toddlers who were considered "picky eaters" had lower
      dietary scores than non-picky eaters, and if family environment and socioeconomic
      status were significantly related to picky eater status and dietary scores.
      METHODS: An incomplete block design provided two interviews at randomly assigned
      times (24, 28, 32, or 36 months) of Caucasian mothers from upper socioeconomic
      (n=74) and lower socioeconomic status (n=44). Using trained interviewers, 6 days
      of food intake, two administrations of a questionnaire about toddler's eating
      behavior, and one administration of the Family Environment Scales were collected
      in the home. MANOVA, discriminant function analysis, and logistic regression
      procedures were used to determine significant differences between picky and non
      picky eater groups. RESULTS: Picky eaters had lower dietary variety (p=.03) and
      diversity scores (p=.009) than non-picky eaters. Mothers of picky eaters compared
      to those of non-picky eaters used persuasion (p=.0001) and ranked their child's
      eating behaviors as more problematic (p=.0001). CONCLUSION: Toddlers perceived by
      their mothers as picky eaters had significantly lower dietary variety and
      diversity scores. Parents need information and strategies to increase the number
      of foods acceptable to their toddlers and to develop a sound feeding plan.

PMID- 9550463
TI  - Repleting hemoglobin in iron deficiency anemia in young children through liquid
      milk fortification with bioavailable iron amino acid chelate.
AB  - OBJECTIVE: To determine if repletion of hemoglobin was achievable in young
      children presenting both severe (< or =9.4 g hemoglobin/dL blood) and less severe
      iron deficiency anemia (9.5 to 11.0 g hemoglobin/dL blood) through fortification
      of liquid 3.3% butterfat milk with a bioavailable ferrous iron amino acid chelate
      (Ferrochel) at 3 mg iron/liter/day. METHODS: A group of 185 children were
      selected from Tupa, Brazil who presented the above two stages of iron deficiency
      anemia plus normalcy. Initially, 54% had severe iron deficiency anemia, 33% were
      less severely anemic and 13% had normal hemoglobin concentrations. They received
      iron-fortified milk for a mean of 222+/-2 days. Hemoglobin concentrations were
      measured initially, at 133+/-13 days, and at 222+/-2 days. RESULTS: By mean 222
      days, 57% of the childrens' hemoglobins were normal. Highest rates of repletion
      were in the initially severe anemic group. Repeated measures ANOVAs demonstrated
      that hemoglobins at 0, 133 and 222 days for the total group, as well as for the
      severe and less severe iron deficiency anemic groups, represented statistically
      different populations at alpha=0.0005. Children with initially normal hemoglobin
      concentrations showed no change at 0, 133 and 222 days (alpha=0.10), suggesting
      the possibility of absorptive regulation of this form of iron. CONCLUSIONS: Low
      hemoglobin concentrations in young children can be increased through daily
      consumption of fluid milk fortified with 3 mg ferrous amino acid chelate
      (Ferrochel).

PMID- 9550465
TI  - Immunopathology of mucous membranes and exocrine glands.

PMID- 9550464
TI  - Confirmation of nasogastric tube placement by colorimetric indicator detection of
      carbon dioxide: a preliminary report.
AB  - BACKGROUND: Inadvertent insertion of nasogastric tubes into the trachea and
      distal airways is reported to range from 0.3% to 15% of insertions. Critically
      ill, mechanically ventilated patients are at a higher risk for such
      complications, some of which can be fatal. OBJECTIVE: This preliminary
      prospective clinical investigation was designed to determine whether a
      colorimetric carbon dioxide (CO2) indicator device (Easy-Cap, Nellcor, Inc.,
      Hayward, CA) attached to the proximal end of a small bore feeding tube (FT) would
      reliably discriminate between those tubes passed into the airways and those
      passed into the alimentary tract. METHODS: Ten critically ill, mechanically
      ventilated trauma patients requiring a FT insertion were evaluated. An Easy-Cap
      device was adapted to the proximal port of each FT. Each patient had one tube
      inserted per the nasogastric route and then another through the endotracheal tube
      while the Easy-Cap was observed for color changes consistent with the presence of
      CO2. RESULTS: All transtracheal insertions showed immediate and unambiguous color
      changes consistent with the presence of CO2. None of the nasogastric insertions
      resulted in indicator color changes and all were confirmed with radiography
      (sensitivity 100%, specificity 100%, accuracy 100%). CONCLUSIONS: This
      preliminary report suggests colorimetric CO2 detection accurately and reliably
      identifies transtracheal FT insertion.

PMID- 9550466
TI  - Bone densitometry: clinical considerations.

PMID- 9550467
TI  - A genome-wide screen for susceptibility loci in ankylosing spondylitis.
AB  - OBJECTIVE: To localize the regions containing genes that determine susceptibility
      to ankylosing spondylitis (AS). METHODS: One hundred five white British families
      with 121 affected sibling pairs with AS were recruited, largely from the Royal
      National Hospital for Rheumatic Diseases AS database. A genome-wide linkage
      screen was undertaken using 254 highly polymorphic microsatellite markers from
      the Medical Research Council (UK) (MRC) set. The major histocompatibility complex
      (MHC) region was studied more intensively using 5 microsatellites lying within
      the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2
      point analysis, and GeneHunter for multipoint analysis. RESULTS: When only the
      MRC set was considered, 11 markers in 7 regions achieved a P value of < or =0.01.
      The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10(-5)) using
      marker D6S273, which lies in the HLA class III region. A further marker used in
      mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10(-9)).
      Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes
      identical by descent across the MHC, suggesting that only 31% of the
      susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD
      score obtained was 2.6 (P = 0.0003) for marker D16S422. CONCLUSION: The results
      of this study confirm the strong linkage of the MHC with AS, and provide
      suggestive evidence regarding the presence and location of non-MHC genes
      influencing susceptibility to the disease.

PMID- 9550468
TI  - Synergistic effect between IL-10 and bcl-2 genotypes in determining
      susceptibility to systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether genes participating in programmed cell death,
      including bcl-2, IL-10, Fas-L, and CTLA-4, may contribute to the genetic
      predisposition to systemic lupus erythematosus (SLE). METHODS: First, intragenic
      markers for the bcl-2, IL-10, Fas-L, and CTLA-4 genes were characterized and
      their extent of polymorphism in normal populations was determined. The allelic
      distribution of these gene markers in a large Mexican American SLE cohort of 158
      patients and 223 ethnically matched controls was determined using fluorescent
      labeled primers and semiautomated genotyping. RESULTS: The bcl-2, Fas-L, and IL
      10 loci showed significantly different allelic distribution in SLE patients
      compared with controls, indicating an association between these genes and SLE. No
      association was found between SLE and the CTLA-4 gene. Further analysis revealed
      a synergistic effect between susceptibility alleles of the bcl-2 and IL-10 genes
      in determining disease susceptibility. Alone, the presence of each of these
      alleles was associated with a moderate increase in SLE risk, while the occurrence
      of these alleles together increased the odds of developing SLE by more than 40
      fold. CONCLUSION: The results suggest that individuals carrying specific
      genotypes of both bcl-2 and IL-10 are at significant risk of developing SLE.

PMID- 9550469
TI  - Influence of antigen organization on the development of lupus autoantibodies.
AB  - OBJECTIVE: To investigate the reason for grouping of antibodies against small
      nuclear RNP (snRNP) particles, which are major autoantigens in systemic lupus
      erythematosus (SLE). METHODS: Mice were immunized with biochemically purified
      native snRNP particles or recombinant proteins, followed by assessment of
      antibody and T cell responses. Since mouse (self) snRNPs are not immunogenic in
      mice, a eukaryotic expression vector was constructed to induce high-level
      expression of the human U1 snRNP-associated A protein in murine cells. Native
      chimeric (mouse/human) snRNP particles were used to immunize normal mice of both
      H-2k and H-2b backgrounds. We also disrupted the native snRNPs by digestion with
      ribonuclease and used this mixture of proteins to immunize mice. RESULTS:
      Immunization with native chimeric snRNPs resulted in the development of
      antibodies against a set of snRNP-associated proteins, a response which was
      accompanied by breakdown in T cell tolerance to mouse snRNPs in mice immunized
      with chimeric snRNPs. We also demonstrated that the ordered production of these
      antibodies was due to the fact that snRNP-associated proteins are grouped
      together in snRNP particles, since disruption of the particles resulted in
      development of antibodies in a random order, distinct from antibodies seen with
      intact particles. CONCLUSION: Our findings directly demonstrate that the pattern
      of development of antibodies to native snRNPs is similar to that which is
      commonly observed in SLE, and that disruption of the particles results in
      disappearance of this ordered pattern. These results suggest that the autoimmune
      response to snRNPs, and possibly to other autoantigens, in lupus is a specific
      reaction similar to that seen in a typical immune response to foreign immunogens.

PMID- 9550470
TI  - Diminished ability of erythrocytes from patients with systemic lupus
      erythematosus to limit opsonized immune complex deposition on leukocytes and
      activation of granulocytes.
AB  - OBJECTIVE: To compare the ability of normal erythrocytes and erythrocytes from
      systemic lupus erythematosus (SLE) patients to bind immune complexes (IC),
      thereby inhibiting IC deposition on polymorphonuclear leukocytes (PMN) and the
      consequent induction of a PMN respiratory burst (RB). METHODS: The binding of
      fluorescein isothiocyanate-labeled IC in 75% autologous serum to whole blood
      cells or isolated leukocytes from 17 SLE patients and 10 controls was assessed by
      flow cytometry. Reactive oxygen metabolite (ROM) production by PMN was measured
      as the intracellular oxidation of dihydrorhodamine 123, on stimulation with
      unlabeled IC. RESULTS: Erythrocyte-mediated inhibition of IC uptake by PMN
      reached a mean +/- SD maximum of 68 +/- 18% in controls and 29 +/- 51% in SLE
      patients (P < 0.05) and, in the patients, correlated inversely with disease
      activity. In the presence of erythrocytes from various donors, IC binding to a
      standard preparation of PMN and their ROM production were inversely proportional
      to the number of type 1 complement receptors (CR1) per donor erythrocyte. Thus,
      the ROM production was higher in the presence of SLE patients' erythrocytes (125
      +/- 67 CR1/erythrocyte) than with erythrocytes from controls (235 +/- 118
      CR1/erythrocyte). CONCLUSION: Erythrocytes from SLE patients are defective in
      protecting their PMN against IC deposition and induction of the RB.

PMID- 9550471
TI  - Platelet-derived growth factor, intimal hyperplasia, and ischemic complications
      in giant cell arteritis.
AB  - OBJECTIVE: To explore whether vasoocclusion in giant cell (temporal) arteritis
      (GCA) is related to intimal hyperplasia and in situ production of platelet
      derived growth factor (PDGF). METHODS: Temporal artery biopsy specimens from
      patients with GCA were analyzed for the presence of intimal hyperplasia.
      Expression of PDGF-A and PDGF-B was assessed by immunohistochemistry and
      digitized image analysis. RESULTS: PDGF-A and PDGF-B were widely expressed in
      inflamed arteries. CD68+ macrophages, smooth muscle cells, and multinucleated
      giant cells produced PDGF, whereas hyperplastic intimal tissue did not. Arteries
      with marked luminal narrowing and those with no or minimal luminal narrowing
      differed in the extent and distribution of PDGF expression. Concentric intimal
      hyperplasia was associated with the accumulation of PDGF-A- and PDGF-B-producing
      CD68+ macrophages at the media-intima junction. PDGF+,CD68+ macrophages in close
      proximity to the internal elastic lamina frequently coproduced matrix
      metalloproteinase 2. Intimal hyperplasia of the temporal artery correlated with
      ischemic complications of GCA, such as ocular involvement, jaw claudication, and
      aortic arch syndrome. CONCLUSION: Production of PDGF has a role in arterial
      occlusion in GCA. The excessive fibroproliferative response leading to luminal
      narrowing can be distinguished from the stenosing process in atherosclerosis and
      postangioplasty restenosis, suggesting that there are different response patterns
      to arterial injury. In GCA, macrophages at the media-intima border are the
      dominant source of PDGF. Since vasoocclusion is associated with a number of
      serious complications in GCA, inhibition of intimal proliferation should be a
      major goal of treatment.

PMID- 9550472
TI  - Reduced cartilage proteoglycan loss during zymosan-induced gonarthritis in NOS2
      deficient mice and in anti-interleukin-1-treated wild-type mice with unabated
      joint inflammation.
AB  - OBJECTIVE: To investigate the role of nitric oxide (NO) and interleukin-1 in (IL
      1) joint inflammation and cartilage destruction during zymosan-induced
      gonarthritis (ZIA). METHODS: Monarticular arthritis was elicited by
      intraarticular injection of zymosan. The effect of NO deficiency on arthritis was
      studied in mice with genetically disrupted NOS2. The role of IL-1 was examined by
      treating wild-type mice with neutralizing anti-murine IL-1(alpha+beta)
      antibodies. Joint swelling was measured externally by the increased uptake of
      circulating 99mtechnetium pertechnetate. Proteoglycan (PG) synthesis was assessed
      using 35S-sulfate incorporation into patellae ex vivo. Histology evaluated
      exudation and infiltration of leukocytes and the extent of cartilage destruction.
      RESULTS: The proinflammatory mediators NO, IL-1, and IL-6 were released by the
      articular tissues during the first hours of inflammation. Interestingly, anti-IL
      1 treatment moderately reduced, and NOS2 deficiency moderately enhanced, joint
      swelling. However, the influx of neutrophils into the joint occurred
      independently of IL-1 and NOS2 activities. In the first week of inflammation,
      chondrocyte PG synthesis was significantly suppressed and chondrocytes became
      unresponsive to their essential anabolic factor, insulin-like growth factor 1
      (IGF-1). Anti-IL-1 treatment or NOS2 deficiency prevented the inhibition of PG
      synthesis, and the chondrocytes remained IGF-1 responsive. Intraarticular
      injections of IL-1alpha into NOS2-deficient mice did not affect PG synthesis,
      thus proving that NO mediated this IL-1 effect in vivo. Furthermore, histology
      showed that cartilage PG loss was markedly ameliorated in NOS2-deficient and anti
      IL-1-treated mice. Intermediate cartilage pathology was found in mice that were
      heterozygous for disrupted NOS2. CONCLUSION: IL-1 and NO play a minor role in
      edema and neutrophil influx, but a major role in cartilage destruction of ZIA. In
      this model of murine arthritis, cartilage destruction was, for the most part,
      caused by pronounced suppression of PG synthesis and IGF-1 unresponsiveness of
      the chondrocytes, which were induced by de novo-synthesized IL-1 and were
      mediated by NOS2 activation.

PMID- 9550473
TI  - Interleukin-1 receptor antagonist prevents expression of the metalloproteinase
      generated neoepitope VDIPEN in antigen-induced arthritis.
AB  - OBJECTIVE: To investigate the relationship between occurrence of the matrix
      metalloproteinase-generated neoepitope VDIPEN and proteoglycan (PG) loss in
      arthritis, and to examine the role of interleukin-1 (IL-1) in VDIPEN expression.
      METHODS: VDIPEN expression was investigated in murine antigen-induced arthritis
      by immunolocalization studies on joint sections. The involvement of IL-1 in
      VDIPEN expression was studied by blocking of IL-1 using IL-1 receptor antagonist
      (IL-1Ra). RESULTS: Profound PG loss was evident early in arthritis, without
      significant VDIPEN expression. Full expression of the neoepitope appeared after a
      few days, when PG depletion was severe, and disappeared at late stages when
      cartilage showed recovery from PG depletion. At sites where chondrocyte death
      occurred and cartilage did not recover from the initial cartilage depletion,
      VDIPEN expression remained present. Prophylactic IL-1Ra treatment of arthritic
      mice resulted in almost complete prevention of VDIPEN expression. However, IL-1Ra
      had only a minor effect on PG depletion, emphasizing that there is no correlation
      between VDIPEN and early PG depletion. CONCLUSION: This study indicates that IL-1
      is involved in VDIPEN expression. Although VDIPEN-inducing metalloproteinases do
      not seem to be involved in early PG depletion during antigen-induced arthritis,
      metalloproteinase neoepitopes are present when PG depletion is severe.

PMID- 9550474
TI  - Soluble Fas ligand in the joints of patients with rheumatoid arthritis and
      osteoarthritis.
AB  - OBJECTIVE: To investigate the expression and function of Fas ligand (FasL),which
      can be in a membrane-bound or soluble form, in the joints of patients with
      rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The concentration of
      soluble FasL (sFasL) in serum and synovial fluid (SF) from 24 OA and 38 RA
      patients was measured using an enzyme-linked immunosorbent assay. The expression
      of FasL on SF lymphocytes (SFL) and peripheral blood lymphocytes (PBL) was
      assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. A
      cytotoxic killing assay of membrane-bound FasL and purified sFasL against
      cultured synovial cells was also performed. RESULTS: Soluble FasL was detected in
      the SF of patients with RA and OA, but not in their serum. The concentration of
      SF sFasL was remarkably higher in patients with severe RA than in patients with
      mild RA or with OA. RT-PCR showed that SFL, but not PBL, from RA patients
      expressed messenger RNA for FasL. Membrane-bound FasL induced apoptosis in
      cultured synovial cells from the RA and OA patients, but naturally processed
      human sFasL did not. CONCLUSION: SFL from RA patients expressed FasL, and cleaved
      sFasL accumulated in the SF of inflamed joints. The different killing activity of
      membrane-bound FasL and sFasL against synovial cells may regulate Fas-mediated
      apoptosis in synovial cells.

PMID- 9550475
TI  - Quantitative microscopic analysis of inflammation in rheumatoid arthritis
      synovial membrane samples selected at arthroscopy compared with samples obtained
      blindly by needle biopsy.
AB  - OBJECTIVE: To evaluate microscopic measures of inflammation in rheumatoid
      arthritis synovial tissue samples selected at arthroscopy compared with those
      obtained blindly by needle biopsy from the suprapatellar pouch (SPP) of the same
      joint. METHODS: Samples were selected at knee arthroscopy from the SPP and the
      lateral and medial gutters. Immediately following arthroscopy, a biopsy needle
      was inserted through the same portal into the SPP by a second investigator, and 3
      further samples were obtained blindly. Using standard immunohistologic methods,
      all samples were analyzed by a single investigator without knowledge of the
      original tissue location and biopsy technique. Following staining with anti-CD3
      and anti-CD68 monoclonal antibodies, T lymphocyte and macrophage infiltration
      were measured by quantitative analysis. RESULTS: Synovial tissues from 14
      patients were analyzed. In comparing microscopic measures of inflammation using
      the 2 procedures, mean scores of lining cell depth and the percentage of CD68+
      cells in the lining layer correlated positively (tau = 0.59, P = 0.003 and tau =
      0.73, P = 0.0003, respectively). In the sublining layer, CD3+ cell counts also
      correlated significantly (tau = 0.71, P = 0.0004). Sublining CD68+ cell counts
      did not correlate. This was explained by the observation that CD68+ cell
      infiltration in areas adjacent to articular cartilage was significantly greater
      than in the SPP (P = 0.01), suggesting preferential trafficking to this site by
      macrophages, but not by T lymphocytes. Macroscopic appearance at arthroscopy did
      not predict microscopic features. CONCLUSION: Most microscopic measures of
      inflammation in synovial tissue samples obtained blindly from the SPP were
      similar to those determined in samples selected at arthroscopy. However,
      measurements in samples from the SPP may underestimate the intensity of
      macrophage infiltration in areas more adjacent to cartilage. These observations
      have important implications for future study of macrophage function in synovial
      tissue.

PMID- 9550476
TI  - Oral iloprost treatment in patients with Raynaud's phenomenon secondary to
      systemic sclerosis: a multicenter, placebo-controlled, double-blind study.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of an oral preparation of
      iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP)
      secondary to systemic sclerosis (scleroderma). METHODS: A multicenter,
      randomized, parallel-group, placebo-controlled double-blind study was performed
      at university and community-based medical centers. Patients were randomly
      assigned to receive either 50 microg of iloprost orally twice daily or an
      identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures
      included average total daily duration of RP attacks, average number of RP
      attacks, and RP condition scored via a standardized daily diary. RESULTS: Three
      hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years
      [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive
      iloprost and 151 to receive placebo. One hundred forty-three patients in the
      iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week
      treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed
      to complete all of the followup visits. The mean reduction in the average
      duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost
      group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean
      reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in
      the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's
      condition score, a patient-completed assessment of the severity of RP attacks,
      was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P =
      0.323). The lack of significant difference between treatment groups did not
      change when a variety of factors, including use of other vasodilators, duration
      of disease, classification of scleroderma (limited versus diffuse), or number of
      baseline digital ulcers were taken into account. Premature withdrawal from the
      study due to adverse events occurred in 10 patients (6.4%) in the iloprost group
      and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION: Oral iloprost at a
      dosage of 50 microg twice daily is no better than placebo for management of RP
      secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of
      posttreatment followup.

PMID- 9550477
TI  - Frequency of recurrent lupus nephritis among ninety-seven renal transplant
      patients during the cyclosporine era.
AB  - OBJECTIVE: To determine the frequency of recurrent lupus nephritis (LN) in
      patients with systemic lupus erythematosus (SLE) who underwent renal
      transplantation. METHODS: We reviewed the posttransplant clinical course and
      renal biopsy results in 97 consecutive SLE patients who underwent a total of 106
      renal transplantation procedures at our center from January 1984 to September
      1996. RESULTS: There were 81 female and 16 male patients, with a mean age of 35
      years. Mean duration of dialysis prior to transplantation was 33.5 months; 9
      patients were never dialyzed. In all patients, the disease was clinically and
      serologically quiescent at the time of transplantation. The mean
      posttransplantation followup period was 62.6 months. Patients underwent a total
      of 143 posttransplant biopsies. Nine patients had pathologic evidence of
      recurrent LN. Six of the patients with recurrence had cadaveric grafts, 2 had
      living-related grafts, and 1 had a living-unrelated graft. Recurrence occurred an
      average of 3.1 years after transplantation; the longest interval was 9.3 years
      and the shortest, 5 days. Histopathologic diagnoses on recurrence included
      diffuse proliferative glomerulonephritis, focal proliferative glomerulonephritis,
      membranous glomerulonephritis, and mesangial glomerulonephritis. In 4 patients,
      recurrent LN contributed to graft loss. Three of the patients with recurrence had
      serologic evidence of active lupus, but only 1 had symptoms of active lupus
      (arthritis). Three patients who lost their grafts secondary to recurrent LN
      underwent second renal transplantation procedures and had functioning grafts at
      7, 30, and 35 months, respectively. CONCLUSION: In the largest single medical
      center series of renal transplant patients with SLE, recurrent LN was more common
      than reported in the literature, but was not always associated with allograft
      loss. Recurrent LN was often present in the absence of clinical and serologic
      evidence of active SLE.

PMID- 9550479
TI  - Characteristic magnetic resonance imaging entheseal changes of knee synovitis in
      spondylarthropathy.
AB  - OBJECTIVE: To use magnetic resonance imaging (MRI) in patients with rheumatoid
      arthritis (RA) and spondylarthropathy (SpA) to determine if the primary site of
      abnormality differs. METHODS: Twenty patients with recent-onset knee effusion (10
      with SpA and 10 with RA) were evaluated using fat-suppressed MRI. Knee joint
      effusion and synovitis were confirmed using ultrasonography. MRI scans were
      independently scored by 2 observers who were blinded to the patient's diagnosis.
      RESULTS: All 10 of the SpA patients, but only 4 of the 10 RA patients, had focal
      peri-entheseal high signal (compatible with fluid or edema) outside the joint (P
      = 0.01). Six of the SpA patients had bone marrow edema that was maximal at
      entheseal insertions; in 4 cases this was multifocal. No RA patients showed such
      an abnormality (P = 0.01). CONCLUSION: Prominent entheseal abnormalities on MRI
      are a consistent feature of new-onset synovitis in SpA, but are a minor feature
      of RA. This finding has important implications for the diagnosis, classification,
      and mechanisms of synovitis in patients with SpA.

PMID- 9550478
TI  - Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after
      twenty-one years, compared with matched controls.
AB  - OBJECTIVE: To study the long-term outcome of surgical removal of a meniscus in
      the knee with regard to radiographic signs of osteoarthritis (OA). METHODS: Of
      the 123 patients who underwent an open meniscectomy due to an isolated meniscus
      tear in 1973 at Lund University Hospital, 107 were followed up 21 years later by
      clinical examination and by review of knee radiographs obtained with weight
      bearing. Seventy-nine of the 107 patients were men, and the mean age of the total
      study group at examination was 55 years (range 35-77). Sixty-eight sex- and age
      matched individuals with healthy knees served as controls. RESULTS: Mild
      radiographic changes were found in 76 (71%) of the knees, while more advanced
      changes, comparable with a Kellgren-Lawrence grade of 2 or higher, were seen in
      51 (48%). The corresponding prevalence values in the control group were 12 (18%)
      and 5 (7%), respectively. The relative risk for the presence of the more advanced
      radiographic changes representing definite radiographic tibiofemoral OA was 14.0
      (95% confidence interval 3.5-121.2), using age- and sex-matched pairs for
      comparison. No correlation with sex, localization to compartment, type of
      meniscus tear, or work load was found. Knee symptoms were reported twice as often
      in the study group as in the controls. CONCLUSION: Surgical removal of a meniscus
      following knee injury represents a significant risk factor for radiographic
      tibiofemoral OA, with a relative risk of 14.0 after 21 years.

PMID- 9550480
TI  - Anticardiolipin antibodies and giant cell arteritis: a prospective, multicenter
      case-control study. Groupe de Recherche sur l'Arterite a Cellules Geantes.
AB  - OBJECTIVE: To assess the prevalence and thrombogenic role of anticardiolipin
      antibodies (aCL) in giant cell arteritis. METHODS: Two hundred eighty-four
      patients with newly diagnosed temporal arteritis or polymyalgia rheumatica and
      210 age- and sex-matched controls randomly selected from the general population
      were included in a multicenter, prospective case-control study. Blood samples
      were obtained at the time of diagnosis, data on initial clinical features were
      collected in a questionnaire, and temporal artery biopsy findings were reviewed
      by an experienced pathologist. RESULTS: Anticardiolipin antibodies were present
      in 20.7% of patients compared with 2.9% of controls (P = 1.45 x 10(-9)). The
      prevalence of aCL was higher in samples found positive for temporal arteritis
      than in those found negative on biopsy (31.2% versus 16.7%; P = 0.04), and was
      similarly higher in the biopsy-positive temporal arteritis group compared with
      the polymyalgia rheumatica and control groups. Although aCL were associated with
      thrombotic complications in univariate analysis, the positivity of the biopsy
      findings remained the only predictive variable in stratified analysis.
      CONCLUSION: In giant cell arteritis, aCL seem to function as reactive antibodies
      in relation to endothelial lesions.

PMID- 9550482
TI  - The association between different patterns of hand symptoms and objective
      evidence of median nerve compression: a community-based survey.
AB  - OBJECTIVE: To examine the association between different patterns of hand symptoms
      and the presence of delayed nerve conduction in the general population. METHODS:
      We performed a 2-stage screening survey involving a questionnaire on current hand
      symptoms, and nerve conduction testing in samples of subjects with and without
      symptoms. Of 648 respondents to the symptom questionnaire, 212 reported hand
      symptoms. In all, 155 were tested for nerve conduction of sensory and motor
      median nerve latencies, including 40 who had reported no symptoms. Patterns of
      hand symptoms were compared with nerve conduction results and associations
      weighted back to the general population. RESULTS: The presence of any hand
      symptoms had only a 40% sensitivity for delayed nerve conduction on latency
      testing. The presence of typical symptoms of carpal tunnel syndrome had a much
      lower sensitivity. CONCLUSION: In a community setting, the distribution of hand
      symptoms does not usefully correlate with the presence of delayed nerve
      conduction in the median nerve.

PMID- 9550481
TI  - Clinical, serologic, and immunogenetic features of familial idiopathic
      inflammatory myopathy.
AB  - OBJECTIVE: To describe the clinical, serologic, and immunogenetic features of
      familial idiopathic inflammatory myopathy (IIM) and to compare these with the
      features of sporadic IIM. METHODS: Clinical signs and symptoms, autoantibodies,
      HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected
      and 28 unaffected members of 16 unrelated families in which 2 or more blood
      relatives developed an IIM. In addition, findings in patients with familial IIM
      were compared with those in 181 patients with sporadic IIM. The families included
      3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with
      other siblings or relatives with polymyositis or dermatomyositis, and 2 families
      with inclusion body myositis. RESULTS: The clinical features of familial IIM were
      similar to those of sporadic IIM, although the frequency of myositis-specific
      autoantibodies was lower in familial than in sporadic IIM. DRB1*0301 was a common
      genetic risk factor for familial and sporadic IIM, but contributed less to the
      genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic
      IIM). Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor
      unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P =
      0.002). CONCLUSION: These findings emphasize that 1) familial muscle weakness is
      not always due to inherited metabolic defects or dystrophies, but may be the
      result of the development of IIM in several members of the same family, and 2)
      multiple genetic factors are likely important in the etiology and disease
      expression of familial IIM, as is also the case for sporadic myositis, but DQA1
      homozygosity is a distinct risk factor for familial IIM.

PMID- 9550483
TI  - Evaluative laboratory testing practices of United States rheumatologists.
AB  - OBJECTIVE: Several laboratory tests can be used to monitor disease activity in
      patients with rheumatic diseases. We sought to learn how rheumatologists use
      evaluative laboratory tests in the care of patients with rheumatoid arthritis
      (RA), systemic lupus erythematosus (SLE), and antineutrophil cytoplasmic antibody
      (ANCA)-associated vasculitis. METHODS: We surveyed United States rheumatologists
      by mailed questionnaire. Of the 976 rheumatologists who received the
      questionnaire, 575 responded, for a response rate of 59%. RESULTS: Eighty-six
      percent of the respondents reported using either the erythrocyte sedimentation
      rate (ESR) or C-reactive protein level to monitor patients with RA, 92% used
      either the anti-DNA antibody level or complement C3 level to monitor patients
      with SLE, and 95% used either the ESR or ANCA levels to monitor patients with
      ANCA-associated vasculitis. The frequency of testing was distributed over a broad
      range, but testing was common. Testing on 50% of the visits or more was reported
      by 52% of respondents for RA, 59% of respondents for SLE, and 64% of respondents
      for ANCA-associated vasculitis. Between 7% and 11% of respondents reported
      testing patients on every visit, regardless of clinical disease activity. The
      majority of respondents reported not altering the treatment of clinically stable
      patients based on these test results. CONCLUSION: Evaluative laboratory testing
      is common, and is rarely used as an independent guide for treatment.

PMID- 9550484
TI  - The camptodactyly-arthropathy-coxa vara-pericarditis syndrome: clinical features
      and genetic mapping to human chromosome 1.
AB  - OBJECTIVE: To delineate the clinical features in patients with the autosomal
      recessive camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) and to
      determine the location of the involved gene. METHODS: Eight affected individuals
      (ages 2-15 years) with CACP from 4 consanguineous kindreds were clinically
      evaluated. Four patients are newly described and 4 have been reported previously.
      Findings were compared with those in 21 other previously reported cases. DNA
      obtained from the 8 affected patients and their available siblings and parents
      was used in a genome-wide search for linkage. RESULTS: Congenital camptodactyly
      and childhood-onset noninflammatory arthropathy were present in all affected
      patients. Seven patients developed bilateral coxa vara deformity, and 1 developed
      coxa magna with cystic erosions. Two of the patients also had symptoms or signs
      of pericarditis. A genome-wide search for linkage identified homozygosity for a
      series of genetic markers on human chromosome 1q in all affected patients. The
      marker D1S191 yielded a maximum logarithm of the odds ratio (LOD score) of 3.3 at
      theta = 0. The CACP gene lies within a 1.9-cM candidate interval defined by the
      markers D1S2107 and D1S222. CONCLUSION: The principal features of the CACP
      syndrome are congenital or early-onset camptodactyly and childhood-onset
      noninflammatory arthropathy. Coxa vara deformity or other dysplasia associated
      with progressive hip disease may develop over time. Clinical pericarditis may
      also occur. A locus responsible for causing CACP syndrome is assigned to a 1.9-cM
      interval on human chromosome 1q25-31 by homozygosity mapping. This now
      facilitates the identification of the responsible gene and permits testing for
      locus homogeneity in other CACP kindreds.

PMID- 9550485
TI  - A prospective study of the safety of joint and soft tissue aspirations and
      injections in patients taking warfarin sodium.
AB  - OBJECTIVE: To determine the safety of joint or soft tissue aspirations and
      injections in patients taking warfarin sodium. METHODS: The outcome of 32 joint
      or soft tissue aspirations or injections in patients receiving stable doses of
      warfarin sodium was assessed through a standardized interview 4 weeks after the
      procedure. The primary outcome measure was significant joint or soft tissue
      hemorrhage, ascertained by patient-reported increases in swelling or warmth at
      the procedure site. RESULTS: None of 32 procedures was complicated by joint or
      soft tissue hemorrhage reported by the patients, yielding, by the "rule of
      threes," a risk of significant hemorrhage of < 10% (with 95% certainty).
      Diagnostic information was obtained for 53% of aspirated sites (8 of 15) and
      therapeutic benefit was noted in 74% of corticosteroid-injected sites (17 of 23).
      CONCLUSION: Joint or soft tissue injections and aspirations in selected patients
      taking warfarin sodium are associated with a low risk of hemorrhage and are often
      of diagnostic or therapeutic value.

PMID- 9550487
TI  - Arthralgias and cryoglobulinemia during protease inhibitor therapy in a patient
      infected with human immunodeficiency virus and hepatitis C virus.
AB  - We present the case of a woman who had a chronic infection with human
      immunodeficiency virus (HIV) and hepatitis C virus (HCV). She developed severe
      polyarthralgias associated with type II mixed cryoglobulinemia during therapy
      with an HIV-1 protease inhibitor. This therapy resulted in a dramatic increase in
      her CD4+ T cell count, from 70/mm3 to 567/mm3, which was composed of a high
      proportion (88%) of naive CD45RA+ CD62L+ cells, together with a recovery of her
      CD4+ T cell reactivity to antigenic stimulation. This may suggest that rapid
      recovery of immune competence in the CD4+ T helper subset might participate in
      the development of immunopathologic events such as this patient's
      cryoglobulinemia.

PMID- 9550488
TI  - Antimalarial drug-induced aquagenic-type pruritus in patients with lupus.

PMID- 9550489
TI  - Association between serum IgG antibodies to recombinant ribosomal P0 fusion
      protein and neuropsychiatric systemic lupus erythematosus.

PMID- 9550490
TI  - Rheumatoid burst fracture.

PMID- 9550491
TI  - Colchicine clearance by high-flux polysulfone dialyzers.

PMID- 9550492
TI  - Updating the American College of Rheumatology criteria for systemic lupus
      erythematosus: comment on the letter by Hochberg.

PMID- 9550493
TI  - The role of microvasculopathy in the catastrophic antiphospholipid syndrome:
      comment on the article by Neuwelt et al.

PMID- 9550494
TI  - New onset of rheumatoid arthritis during interferon beta-1B treatment in a
      patient with multiple sclerosis: comment on the case report by Jabaily and
      Thompson.

PMID- 9550495
TI  - Mycoplasmas in the joints of patients with rheumatoid arthritis and other
      inflammatory rheumatic disorders: comment on the article by Hoffman et al.

PMID- 9550496
TI  - HLA phenotype and systemic sclerosis-rheumatoid arthritis overlap syndrome:
      comment on the article by Horiki et al.

PMID- 9550497
TI  - Neck injury and chronic pain syndromes: comment on the article by Buskila et al.

PMID- 9550498
TI  - Fibroblastic rheumatism: a fifteen-year followup study.

PMID- 9550499
TI  - Cholesterol lowering in the management of coronary artery disease: the clinical
      implications of recent trials.
AB  - Atherosclerotic vascular disease is the major cause of death and disability in
      adult men and women living in the United States, where 13-14 million adults have
      a history of coronary artery disease (CAD). One-third of the 1.5 million
      individuals who experience a myocardial infarction (MI) each year will die and
      one half of these deaths will occur within 60 minutes of the event. The relation
      between elevated serum lipids and CAD has been corroborated by epidemiologic as
      well as pathologic evidence. Approximately 96 million people have total
      cholesterol levels > 200 mg/dL, with 38 million of these individuals having
      values > 240 mg/ dL. The National Cholesterol Education Program (NCEP) identified
      elevated low-density lipoprotein (LDL) cholesterol as a primary risk factor for
      CAD in 1988. This conclusion, along with recommendations for assessment and
      treatment, was reaffirmed in 1993. The NCEP also recommended that high-risk
      patients, with or without clinical manifestations of coronary atherosclerosis,
      should substantially lower their serum cholesterol levels. Specifically, the NCEP
      recommends that patients with CAD need to maintain serum LDL cholesterol levels
      of < or = 100 mg/dL; this means that the vast majority of patients need to
      decrease LDL cholesterol levels by > or = 30%. Aggressive dietary and/or drug
      therapy are recommended to achieve these reductions. In recent years, clinical
      trials have demonstrated the efficacy of 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitors ("statins") in lowering elevated levels of LDL
      cholesterol and decreasing the risk for clinical coronary events.

PMID- 9550500
TI  - Risk factor modification: rationale for management of dyslipidemia.
AB  - A number of recent clinical trials have clearly demonstrated the efficacy of
      cholesterol lowering as a risk-reduction strategy for the primary and secondary
      prevention of coronary artery disease (CAD). The Scandinavian Simvastatin
      Survival Study (4S), the West of Scotland Coronary Prevention Study (WOSCOPS),
      and the Cholesterol and Recurrent Events (CARE) trial, as well as numerous other
      investigations, have established that decreasing elevated levels of low-density
      lipoprotein (LDL) cholesterol will result in a reduction in CAD risk. This has
      been reported since the 1980s, when the first of the 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors ("statins") became available. These
      drugs were an important advance because they showed better patient compliance due
      to fewer side effects when compared with other lipid-lowering agents.
      Nonetheless, many physicians, for various reasons, have not done an adequate job
      of ensuring that the millions of patients who could benefit from lipid-lowering
      therapy actually receive the treatment they require.

PMID- 9550501
TI  - Therapeutic efficacy of the lipid-lowering armamentarium: the clinical benefits
      of aggressive lipid-lowering therapy.
AB  - Hypercholesterolemia, particularly an elevated level of low-density lipoprotein
      (LDL) cholesterol, is an unarguably established risk factor for coronary artery
      disease (CAD). It is equally well established that lowering LDL cholesterol
      levels will decrease CAD-related morbidity and mortality in patients with
      established CAD. Although lipid-lowering therapy is known to retard the
      progression of atherosclerosis in patients with native coronary arteries, its
      effect in patients with coronary bypass grafts, which are particularly vulnerable
      to occlusion, is less well understood. Moreover, whereas several major clinical
      trials have documented the benefits of lowering LDL cholesterol in a variety of
      patient subpopulations, there has been far less clarity surrounding the question
      of whether aggressive lowering of LDL cholesterol is of greater benefit than
      moderate lowering of LDL cholesterol. The Post Coronary Artery Bypass Graft (Post
      CABG) trial, a multicenter, randomized, double-blind clinical trial comprising
      1,351 patients with elevated levels of LDL cholesterol and a history of bypass
      surgery was designed to determine whether aggressive lowering of LDL cholesterol
      levels with therapy based on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors ("statins") is more effective than moderate lowering in
      delaying the progression of atherosclerosis in bypass grafts. Quantitative
      computer-assisted angiography was conducted at baseline and again at an average
      of 4.3 years. The primary angiographic outcome was the mean percentage per
      patient of grafts with a decrease of > or = 0.6 mm in lumen diameter. Patients
      who received aggressive therapy were significantly more likely than their
      moderate-treatment counterparts to achieve and maintain LDL cholesterol levels
      within the National Cholesterol Education Program's (NCEP's) recommended target
      of < or = 100 mg/dL (< or = 2.59 mmol/L). Moreover, the mean percentage of grafts
      with progression of atherosclerosis was 27% for aggressively treated patients,
      compared with 39% for those who were randomized to the moderate-treatment group
      (p < 0.001). This study demonstrates that aggressive lipid lowering is practical
      and worthwhile in at-risk patients. Aggressive treatment is far more effective
      than moderate treatment in lowering LDL cholesterol levels to the NCEP target
      level of < or = 100 mg/dL (< or = 2.59 mmol/L), and this intervention decreases
      the progression of atherosclerosis.

PMID- 9550502
TI  - Current concepts in cardiovascular pathology: the role of LDL cholesterol in
      plaque rupture and stabilization.
AB  - Emerging evidence is redefining traditional concepts of coronary atherosclerosis.
      Recent data indicate that severe stenoses, the traditional focus of attention, do
      not cause most coronary events. Rather, interest has increased in the often less
      stenotic but more vulnerable lesions that are characterized by thin fibrous caps,
      large lipid accumulations, large numbers of macrophages, and depletion of smooth
      muscle cells. Such lesions appear prone to rupture, which allows the blood to
      come into contact with the highly thrombogenic material in the lipid core of the
      plaque, thereby precipitating thrombosis. The fibrous cap may become weakened
      through decreased synthesis of the extracellular matrix or increased degradation
      of the matrix. The cytokine interferon-gamma, produced by T-lymphocytes, inhibits
      the ability of smooth muscle cells to synthesize collagen, a structurally
      important component of the fibrous cap. A family of enzymes known as matrix
      metalloproteinases can degrade all major constituents of the vascular
      extracellular matrix: collagen, elastin, and proteoglycans. Additional studies on
      the biochemical mechanisms of atherosclerosis may provide a fuller understanding
      of the ways in which lipid-lowering therapy can confer clinical benefit.

PMID- 9550503
TI  - Profiling risk and new therapeutic interventions: looking ahead.
AB  - The benefits of cholesterol lowering for primary and secondary prevention of
      coronary artery disease (CAD) have been well established. However, to accurately
      assess a patient's risk for CAD, clinicians must be aware of their patients'
      specific levels of low-density lipoprotein (LDL) cholesterol, high-density
      lipoprotein (HDL) cholesterol, and triglycerides, and not just total serum
      cholesterol. Clinicians must also evaluate other factors in assessing a patient's
      risk profile. These include smoking, weight, family history of CAD, age,
      hypertension, and others. Absolute risk, rather than relative risk, can then be
      determined. Although LDL cholesterol may be the most potent predictor of risk,
      triglycerides are also an important indicator of CAD risk. Currently, 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") are first
      line therapy for the reduction of elevated levels of LDL cholesterol. All statins
      are effective in achieving some level of LDL cholesterol lowering. However,
      atorvastatin, which was recently introduced in the United States, has greater
      efficacy at maximal dosage in lowering LDL cholesterol, and also has a more
      beneficial effect on elevated levels of triglycerides, than other statins.

PMID- 9550504
TI  - Risk reduction therapies for patients with coronary artery disease: a call for
      increased implementation.
AB  - Recent decades have witnessed significant advances in the use of interventional
      procedures and medical therapies for relief of symptoms associated with
      obstructive coronary artery disease (CAD). At the same time, however, little
      progress has been made in understanding and implementing preventive therapy and
      risk reduction. Our traditional focus on treatment of severe coronary obstruction
      has addressed only part of the problem. We now need to adopt a more comprehensive
      approach aimed at the entire spectrum of atherosclerotic disease. Numerous
      clinical trials have demonstrated that risk-reduction strategies can produce
      marked decreases in the incidence of cardiovascular events as well as in total
      mortality. Despite this strong body of evidence, risk-reduction therapies
      continue to be underutilized. Comprehensive changes in healthcare delivery
      systems are needed to ensure that risk-reduction strategies become a routine part
      of care for patients with cardiovascular disease.

PMID- 9550505
TI  - Hypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian
      Hemodilution Stroke Trial (MAHST).
AB  - BACKGROUND AND PURPOSE: Experimental studies suggest a beneficial effect of
      hemodilution on acute ischemic stroke. This was not proven by previous
      multicenter trials in the clinical setting. Various reasons have been suggested
      for the failure of these studies, which we attempted to consider in the
      Multicenter Austrian Hemodilution Stroke Trial (MAHST). METHODS: MAHST is a
      randomized, double-blind, placebo-controlled study of hypervolemic hemodilution
      (HHD) within 6 hours of a clinically first ischemic stroke localized in the
      middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl
      starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's
      lactate over a period of 5 days. Our primary outcome measure was clinical
      improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We
      performed an adaptive interim analysis to reevaluate the study goal after
      entering half of the projected number of patients (n = 200). At least 600
      patients per group would have been required for significant results, and
      therefore we decided to terminate the trial. RESULTS: Ninety-eight patients
      received HHD and 102 patients placebo. The baseline characteristics were
      comparable between both groups. In the HHD group the absolute reduction of the
      hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with
      a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat
      analysis showed no significant difference of the change of the GNS scores between
      HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo
      treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7,
      and GNS scores remained similar in both treatment groups throughout the trial. At
      3 months, slightly more HHD patients showed complete independence on the Barthel
      Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus
      17), but these differences were not statistically significant. HHD treatment was
      not associated with any specific adverse event. CONCLUSIONS: Mild HHD is safe but
      failed to demonstrate a significant beneficial effect over the pure rehydration
      regimen in patients with acute ischemic stroke.

PMID- 9550506
TI  - Multicenter review of preoperative risk factors for endarterectomy for
      asymptomatic carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: The benefit of carotid endarterectomy is highly dependent
      on surgical risk. However, little data are available concerning factors affecting
      the risk of endarterectomy performed for asymptomatic carotid artery stenosis
      outside the setting of a randomized controlled trial. The purpose of this study
      was to analyze the impact of potential preoperative risk factors on the frequency
      of postoperative complications in patients undergoing the operation for
      asymptomatic disease in academic medical centers. METHODS: Data regarding
      postoperative complications were systematically abstracted from the medical
      records of a random sample of patients who underwent carotid endarterectomy at 12
      academic medical centers. RESULTS: Of 1160 procedures reviewed, 463 (40%) were
      performed for asymptomatic disease. Postoperative stroke or death occurred in 13
      (2.8%), and myocardial infarction occurred in 8 (1.7%). The rate of postoperative
      stroke or death was lower in asymptomatic patients than in those with a history
      of cerebrovascular symptoms in a different vascular distribution, but the
      difference was not significant (1.8% versus 4.2%; P=.21). There were no
      significant differences in these rates based on race, a history of angina, recent
      myocardial infarction, chronic obstructive pulmonary disease, hypertension, the
      degree of stenosis of the contralateral or ipsilateral carotid artery, or the
      presence of angiographically recognized ulceration, intraluminal thrombus, or
      siphon stenosis in the ipsilateral vessel (chi(2); P>.05). Postoperative stroke
      or death was more frequent in women (5.3% versus 1.6% in men; P=.02), in those
      aged 75 years or older (7.8% versus 1.8% in those younger than 75 years; P=.01),
      and in those with a history of congestive heart failure (8.6% versus 2.3% in
      those without a history of congestive heart failure; P=.03). The risk of stroke
      or death was higher in the 16 patients who had carotid endarterectomy performed
      in combination with coronary artery bypass surgery than in those who had only
      endarterectomy (18.7% versus 2.1%; P<.001). CONCLUSIONS: The overall risk of
      postoperative stroke or death was nearly twice that reported by Asymptomatic
      Carotid Atherosclerosis Study (ACAS) investigators in the setting of a clinical
      trial but was within acceptable guidelines. Women were at higher postoperative
      risk than men, which supported ACAS findings. Additional high-risk groups were
      those aged 75 years or older, those with a history of congestive heart failure,
      and those undergoing prophylactic endarterectomy for asymptomatic stenosis in
      combination with coronary surgery. Knowledge of these rates may help to better
      assess an individual's postoperative risk and therefore the anticipated benefit
      of surgery.

PMID- 9550507
TI  - Increased oxygen extraction fraction is associated with prior ischemic events in
      patients with carotid occlusion.
AB  - BACKGROUND AND PURPOSE: The purpose of our study was to investigate the
      relationship between misery perfusion (increased oxygen extraction fraction, OEF)
      and baseline risk factors in patients with carotid occlusion. METHODS: One
      hundred seventeen patients with atherosclerotic carotid occlusion were studied
      prospectively by clinical evaluation, laboratory testing, and positron emission
      tomography (PET). PET measurements of cerebral blood flow (CBF), cerebral blood
      volume (CBV), and OEF were made on enrollment in the study. Increased ipsilateral
      OEF was identified by comparison with 18 normal control subjects. Twenty-five
      baseline clinical, epidemiological, and arteriographic risk factors were assessed
      on study entry. Student t tests, chi(2) tests, and Fisher exact tests with
      Bonferroni correction were used to assess statistical significance (P<.05).
      RESULTS: Of 117 patients, 44 had increased OEF distal to the occluded carotid and
      73 had normal OEFs. Thirty-nine of the 81 patients with prior ipsilateral
      ischemic symptoms had high OEFs (42%), whereas only 5 of the 31 asymptomatic
      patients had high OEFs (16%, P<.001). All of the other baseline risk factors were
      similar between the two groups of patients. CONCLUSIONS: Investigations of the
      relationship between hemodynamic factors and stroke risk must take into account
      the lower frequency of hemodynamic abnormalities in asymptomatic patients.

PMID- 9550508
TI  - Subclinical atherosclerosis in relation to hysterectomy status in black women.
AB  - BACKGROUND AND PURPOSE: This study was designed to investigate whether black
      women who underwent hysterectomy only (n = 59) or hysterectomy plus bilateral
      oophorectomy (n=25) were at increased risk of subclinical carotid atherosclerosis
      compared with black women who underwent natural menopause (n = 54). The effects
      of both surgery and menopausal status were evaluated. METHODS: Women aged 34 to
      58 years were recruited from the Pittsburgh, Pa, area. Postmenopausal status was
      defined as a serum follicle-stimulating hormone level of >30 mIU/mL. Carotid
      duplex scans were performed to assess the degree of focal plaque. RESULTS: Among
      premenopausal women, focal plaque was present in 20% of nonhysterectomized versus
      49% of hysterectomized-only women (P=.004). Among postmenopausal women, plaque
      was present in 69% of nonhysterectomized women, 86% of women with hysterectomy
      only, and 48% of women with oophorectomy and hysterectomy (P=.056). Among
      postmenopausal women, hormone replacement therapy was used by 23% of women who
      had undergone natural menopause, 0% of women with hysterectomy only, and 36% of
      women with oophorectomy and hysterectomy. The prevalence of plaque was 33% among
      hormone replacement therapy users versus 73% among nonusers (P=.014). In
      multivariate analysis, independent associations with the presence of at least 1
      plaque were postmenopausal status and hysterectomy only. CONCLUSIONS: These data
      suggest that black women who undergo hysterectomy without oophorectomy may be at
      higher risk of subclinical carotid atherosclerosis than black women who undergo
      natural menopause or hysterectomy plus oophorectomy.

PMID- 9550509
TI  - Relationship between blood pressure and subcortical lesions in healthy elderly
      people.
AB  - BACKGROUND AND PURPOSE: The relationship between blood pressure (BP) and heart
      rate (HR) and MRI assessments of subcortical T2 hyperintensities was evaluated in
      healthy elderly men and women. METHODS: Casual and 24-hour ambulatory BPs and HR
      measurements were taken of 144 elderly individuals, aged 55 to 79 years. Subjects
      had no evidence of previous health disorders. MRI scans of white matter,
      subcortical gray matter, and insular subcortex were coded for severity of
      hyperintensities. RESULTS: Mean casual BP for the group was 120/72 mm Hg. With
      age and sex accounted for, individuals with the highest severity rating of white
      matter hyperintensities had higher casual, awake, and sleep systolic BPs; higher
      awake diastolic BPs; greater awake systolic BP variability; and a smaller
      nocturnal fall in systolic and diastolic BPs than individuals with less severe
      ratings. Higher severity ratings for subcortical gray matter hyperintensities
      were associated with elevations in casual, awake, and asleep systolic BPs and a
      smaller HR drop during sleep. Subjects with higher ratings for the insular
      subcortex had higher systolic and diastolic BPs (casual, awake, and asleep),
      greater HR variability during sleep, and a smaller nocturnal fall in HR.
      CONCLUSIONS: Casual and 24-hour ambulatory BPs and some ambulatory HR measures
      are associated with subcortical lesions of the brain. Longitudinal studies are
      needed to further explore the relationship between white matter lesions and
      cardiovascular measures, as well as the significance of these lesions for
      cerebrovascular disease in healthy elderly subjects.

PMID- 9550510
TI  - Distribution of Chlamydia pneumoniae infection in the athersclerotic carotid
      artery.
AB  - BACKGROUND AND PURPOSE: Chlamydia pneumoniae infection has recently become
      noteworthy in relation to atherosclerosis. We investigated by
      immunohistochemistry the distribution of C pneumoniae infection in the
      atherosclerotic carotid artery. METHODS: Twenty carotid atherosclerotic lesions
      that were resected during carotid endarterectomy were investigated. Parallel
      sections were stained immunohistochemically with monoclonal antibodies for a C
      pneumoniae-specific antigen, macrophages, and smooth muscle cells. RESULTS:
      Immunoreactivity for the C pneumoniae-specific antigen was observed in 11 of 20
      specimens (55%), and intense immunoreactivity was observed in 7 of 20 (35%). C
      pneumoniae infection was observed in endothelial cells, macrophages and in smooth
      muscle cells that had migrated into the atheromatous plaque, as well as in smooth
      muscle cells and small arteries in the media underlying the atheromatous plaques.
      C pneumoniae infection was most prominently observed in smooth muscle cells. The
      severity of the infection as demonstrated by immunohistochemistry was not
      significantly related to general risk factors for atherosclerosis. CONCLUSIONS: C
      pneumoniae widely infects endothelial cells, macrophages, and smooth muscle cells
      in the atherosclerotic carotid artery. The results of the present study can help
      us to understand how C pneumoniae infection contributes to the progression of
      carotid atherosclerosis.

PMID- 9550511
TI  - Outcome of subacute stroke rehabilitation: a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Organized acute stroke treatment reduces mortality,
      functional deficits, and the need of institutionalization after stroke. It is
      largely unknown whether the effects of treatment are due to early or subacute
      efforts. The aim of this randomized, controlled study was to test the hypothesis
      that rehabilitation of stroke patients in the subacute phase in a hospital
      rehabilitation unit is beneficial in reducing death and dependency and increasing
      health-related quality of life. METHODS: 251 patients initially treated in the
      hospital were randomized to subacute rehabilitation in a hospital rehabilitation
      unit (n = 127) or to the health services in the municipality (n = 124) and were
      followed up for 7 months. RESULTS: The combined outcome of patients being dead or
      dependent (Barthel Index score of < 75) was 23% in the hospital group and 38% in
      the municipality group (P=.01). Seven-month survival rates were 90.6% and 83.9%
      (P=.11), respectively. Dependency in activities of daily living was 12.6% in the
      hospital group and 25.0% in the municipality group (P=.07). Patients with a BI
      score of < 50 before rehabilitation had significantly better outcome in the
      hospital rehabilitation unit, with fewer patients becoming dependent (P=.005) and
      patients having higher Scandinavian Stroke Scale (P=.026) and BI scores (P=.005).
      No significant differences in health-related quality of life were found. Many
      patients treated in the municipalities (30%) did not receive any organized
      rehabilitation in this study. CONCLUSIONS: Subacute rehabilitation of stroke
      patients in a hospital-based rehabilitation unit improves outcome. Patients with
      moderate or severe stroke appear to benefit most.

PMID- 9550512
TI  - Effect of a therapeutic intervention for the hemiplegic upper limb in the acute
      phase after stroke: a single-blind, randomized, controlled multicenter trial.
AB  - BACKGROUND AND PURPOSE: Arm function recovery is notoriously poor in stroke
      patients. The effect of treatment modalities, particularly those directed at
      improving upper limb function, has been studied primarily in chronic stroke
      patients. The purpose of this study was to investigate the effect of a specific
      therapeutic intervention on arm function in the acute phase after stroke.
      METHODS: In a single-blind, randomized, controlled multicenter trial, 100
      consecutive patients were allocated to either an experimental group that received
      an additional treatment of sensorimotor stimulation or to a control group. The
      intervention was applied for 6 weeks. Patients were evaluated for level of
      impairment (Brunnstrom-Fugl-Meyer test) and disability (Action Research Arm test,
      Barthel Index) before, midway, and after the intervention period and at follow-up
      6 and 12 months after stroke. RESULTS: Patients in the experimental group
      performed better on the Brunnstrom-Fugl-Meyer test than those in the control
      group throughout the study period, but differences were significant only at
      follow-up. Results on the Action Research Arm test and Barthel Index revealed no
      effect at the level of disability. The effect of the therapy was attributed to
      the repetitive stimulation of muscle activity. The treatment was most effective
      in patients with a severe motor deficit and hemianopia or hemi-inattention. No
      adverse effects due to the intervention were found. CONCLUSIONS: Adding a
      specific intervention during the acute phase after stroke improved motor
      recovery, which was apparent 1 year later. These results emphasize the potential
      beneficial effect of therapeutic interventions for the arm.

PMID- 9550514
TI  - Quality of life in patients and partners after aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Outcome after subarachnoid hemorrhage (SAH) is often
      graded as "poor," "fair," or "good." Such categories are usually based on
      physicians' assessments of physical abilities of patients rather than on how
      patients themselves perceive their physical, psychological, and social well
      being. We assessed functional outcome and quality of life (QoL) in patients with
      SAH and their partners. METHODS: In a consecutive series of 64 patients and 51
      partners studied 4 months after the SAH, we assessed functional outcome by means
      of the Rankin Scale, and QoL by means of the SF-36, the Sickness Impact Profile
      (SIP), and a visual analogue scale. Additionally, we asked two "simple questions"
      about dependency and recovery. All questionnaires were completed in an interview
      setting. The scores on the QoL instruments from patients and partners were
      stratified according to the Rankin grades of the patients and were compared with
      data from a Dutch reference population. RESULTS: Only patients who had no
      symptoms at all (Rankin grade 0) had no reduction in QoL compared with the
      reference population; some of these patients even indicated an improvement in QoL
      from before the SAH according to the visual analogue scale. Patients who had
      symptoms but were independent (Rankin grades 1 to 3) and therefore usually
      designated as having "good outcome" often had reductions in QoL, on both the
      physical and psychosocial subscores of the SIP and SF-36. The QoL of partners was
      considerably reduced in several psychosocial domains. CONCLUSIONS: SAH has a
      considerable impact on the QoL of patients and their partners. Only patients
      without residual symptoms (Rankin grade 0) have a good outcome in terms of
      physical performance and QoL.

PMID- 9550513
TI  - Survival and functional status 20 or more years after first stroke: the
      Framingham Study.
AB  - BACKGROUND AND PURPOSE: We examined the 20-or-more-year survival and functional
      levels of 148 stroke survivors and 148 age- and sex-matched control subjects from
      the Framingham Study Cohort, whom we originally studied in 1972-1974 to ascertain
      the survival and disability status of stroke survivors compared with that of
      controls. METHODS: This long-term evaluation was done with use of data from the
      1993-1995 Framingham Study Cohort Examination 23 on the 10 stroke survivors and
      20 control subjects still living to identify and compare the host characteristics
      and functional status of each group. The survival curves for both stroke
      survivors and controls were derived from the ongoing Framingham Study database.
      RESULTS: Twenty-plus-year stroke survivors experienced a greater mortality than
      age- and sex-matched controls (92.5% and 81%, respectively). The slopes of the
      two survival curves were essentially the same. Functional status (eg, walking and
      independence in activities of daily living) of stroke survivors, however,
      compared very favorably with that of the control subjects. Stroke survivors were
      more likely to be female and to have a number of comorbidities, including
      elevated blood pressures, greater use of medications, less use of alcohol, and
      less depressive symptomology. CONCLUSIONS: In the Framingham cohort, 20-plus-year
      stroke survivors showed greater mortality than age- and sex-matched control
      subjects; functionally, however, the groups were very similar and in general
      quite independent.

PMID- 9550515
TI  - Intellectual decline after stroke: the Framingham Study.
AB  - BACKGROUND AND PURPOSE: The causes and characteristics of cognitive decline after
      stroke are poorly defined, because most studies have relied on the diagnosis of
      dementia after stroke, without measurement of prestroke cognitive function.
      METHODS: The Mini-Mental State Examination (MMSE) was used to assess the
      cognitive performance of 74 subjects from the Framingham Study cohort who had
      suffered a stroke during a 13-year period. We compared their poststroke cognitive
      performance with the prestroke MMSE scores collected during their biennial
      examinations, and their prestroke/poststroke changes in MMSE score were then
      compared with those of 74 control subjects matched for age and sex. Cases and
      controls underwent testing for symptoms of depression using the Center for
      Epidemiologic Studies of Depression (CES-D) scale, and these findings were
      correlated with their cognitive performance. Changes in cognitive performance in
      the cases were correlated with the CT-documented characteristics of the stroke.
      RESULTS: The cases had a significantly lower mean+/-SE MMSE score at prestroke
      baseline (27.28+/-0.34) than did the control subjects (28.08+/-0.21), a
      difference that became more pronounced (23.57+/-0.92 versus 28.31+/-0.25; P<.001)
      after stroke. The poststroke decline in cognitive function in the cases was
      correlated only with a large, left-sided stroke on CT. The CES-D scores were
      significantly higher in the cases, but nondepressed cases had significantly lower
      MMSE scores than nondepressed controls. CONCLUSIONS: Stroke is followed by a
      significant decline in cognitive performance when prestroke and poststroke
      measurements are compared. Although depression is more frequent in the stroke
      patients, their intellectual decline appears to be independent from the presence
      of depression.

PMID- 9550516
TI  - Factor XIII Val 34 Leu: a novel association with primary intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: A common G-to-T point mutation (Val 34 Leu) in exon 2 of
      the alpha-subunit of the factor XIII is strongly negatively associated with the
      development of myocardial infarction. This result suggests that factor XIII Val
      34 Leu is interfering with the formation of cross-linked fibrin. The role of
      factor XIII Val 34 Leu in the pathogenesis of cerebral infarction and primary
      intracerebral hemorrhage is unknown. METHODS: Six hundred twelve patients with
      acute stroke, defined by World Health Organization criteria and cranial CT, and
      436 age-matched control subjects free of cerebrovascular disease were genotyped
      for the factor XIII Val 34 Leu mutation. Venous blood was drawn for the
      determination of hemostatic variables and lipids. Factor XIII genotype was
      determined through a single-stranded conformational polymorphism technique and
      plasminogen activator inhibitor (PAI)-1 4G/5G promoter genotype by allele
      specific polymerase chain reaction. RESULTS: The mutation was more frequent in
      patients with primary intracerebral hemorrhage (n=62) (54.8%; P=.05) than in
      control subjects (41.7%) or in patients with cerebral infarction (n=529) (46.5%;
      P=.22). There was no relationship between PAI-1 levels and the PAI-1 4G/5G
      genotype. CONCLUSIONS: There was a slightly higher incidence of factor XIII Val
      34 Leu in patients with PICH. This may be related to impaired cross-linking of
      fibrin and/or coagulation proteins.

PMID- 9550517
TI  - Antioxidants inhibit ATP-sensitive potassium channels in cerebral arterioles.
AB  - BACKGROUND AND PURPOSE: Hydrogen peroxide and peroxynitrite are capable of
      generating hydroxyl radical and are commonly suspected as sources of this radical
      in tissues. It would be useful to distinguish the source of hydroxyl radical in
      pathophysiological conditions and to clarify the mechanisms by which antioxidants
      modify vascular actions of oxidants. METHODS: We investigated the effect of three
      antioxidants--dimethylsulfoxide (DMSO), salicylate, and L-cysteine--on the
      cerebral arteriolar dilation caused by topical application of hydrogen peroxide
      and peroxynitrite in anesthetized cats equipped with cranial windows. We also
      tested the effect of these antioxidants on the vasodilation caused by pinacidil
      and cromakalim, two known openers of ATP-sensitive potassium channels. RESULTS:
      DMSO was more effective in inhibiting dilation from hydrogen peroxide, whereas
      salicylate and L-cysteine were more effective in inhibiting dilation from
      peroxynitrite. All three antioxidants inhibited dilation in concentrations that
      were remarkably low (< 1 mmol/L). All three antioxidants inhibited vasodilation
      from two known potassium channel openers, pinacidil and cromakalim. Their effect
      was specific because they did not affect dilation from adenosine or
      nitroprusside. CONCLUSIONS: The findings show that antioxidants block ATP
      sensitive potassium channels in cerebral arterioles. This appears to be the
      mechanism by which antioxidants inhibit the dilation from hydrogen peroxide and
      peroxynitrite and not through scavenging of a common intermediate, ie, hydroxyl
      radical. The differences between effectiveness in inhibiting dilation from
      hydrogen peroxide and peroxynitrite by various antioxidants suggest that hydrogen
      peroxide and peroxynitrite act at two different sites, one in a water-soluble
      environment and the other in a lipid-soluble environment.

PMID- 9550518
TI  - Treatment with the competitive NMDA antagonist GPI 3000 does not improve outcome
      after cardiac arrest in dogs.
AB  - BACKGROUND AND PURPOSE: We previously showed that treatment with a competitive N
      methyl-D-aspartate (NMDA) receptor antagonist GPI-3000 (GPI) improved short-term
      physiological recovery after incomplete global cerebral ischemia complicated by
      dense acidosis. We tested the hypothesis that GPI administered after
      resuscitation from cardiac arrest would improve a more long-term recovery as
      measured by neurobehavioral assessment and neuropathology 4 days after
      resuscitation. METHODS: Anesthetized dogs were subjected to 7 minutes of cardiac
      arrest followed by vest cardiopulmonary resuscitation. Neurobehavioral outcomes
      were scored daily on a score ranging from 0 (normal) to 500 (worst). On the
      fourth day, the animals were killed, and neuropathology was evaluated in a
      blinded manner in the hippocampus and the neocortex by hematoxylin and eosin
      staining and by determination of percentage of injured neurons. Three groups of
      animals were treated in a randomized, blinded protocol with either saline (SAL),
      low-dose GPI (5 mg/kg followed by 1 mg/kg per hour for 2 hours), or high-dose GPI
      (25 mg/kg, followed by 5 mg/kg per hour for 2 hours). RESULTS: The mortality rate
      was higher in animals receiving GPI than in saline-treated control animals (4 of
      15 deaths in SAL, 6 of 15 in the low-dose GPI group, and 9 of 18 in the high-dose
      GPI group). Neurobehavioral scores were depressed in GPI-treated animals compared
      with saline-treated control animals in a dose-dependent manner, with 96-hour
      scores of essentially normal (9+/-2) in saline-treated animals compared with
      those animals with significant impairment (181+/-47) treated with high-dose GPI.
      Neuropathological damage in the neocortex was most severe in GPI-treated animals,
      with the percentage of injured neurons dependent on the dose: 8.3%+/-2.7% SAL,
      13.2%+/-6.4% low-dose GPI, and 39.4%+/-10.1%, high-dose GPI. CA1 neuronal damage
      was severe regardless of treatment. CONCLUSIONS: Contrary to results seen in
      experimental global and focal cerebral ischemia, in which NMDA receptor
      antagonism may improve responses to injury, receptor antagonism with GPI does not
      improve brain outcome after cardiac arrest and resuscitation in the dog.
      Behavioral and histological outcomes both were worsened by GPI treatment at two
      doses, and mortality was higher relative to saline control treatment. We
      speculate that systemic drug effects, as well as potential neurotoxicity of the
      drug under ischemic conditions, may be responsible for the deleterious outcomes
      observed in our cardiac arrest model.

PMID- 9550519
TI  - Inhibition of poly(ADP-ribose) polymerase: reduction of ischemic injury and
      attenuation of N-methyl-D-aspartate-induced neurotransmitter dysregulation.
AB  - BACKGROUND AND PURPOSE: The nuclear enzyme poly(ADP-ribose) polymerase (PARP) may
      play a role in DNA repair. However, in cerebral ischemia, excessive PARP
      activation may lead to energy depletion and exacerbation of neuronal damage. We
      examined the effect of inhibiting PARP on (1) the degree of cerebral injury in a
      rat model of transient focal ischemia and (2) the degree of neurotransmitter
      dysregulation induced by local cortical perfusion of N-methyl-D-aspartate (NMDA).
      METHODS: In experiment 1, rats were subjected to transient ischemia for 90
      minutes by occlusion of the middle cerebral artery. After 22.5 hours of
      reperfusion, lesions were quantified by tetrazolium staining. Untreated rats were
      compared with those treated with the PARP inhibitor 3-aminobenzamide (10 mg/kg).
      In experiment 2, rats were implanted with microdialysis probes in the cortex, and
      1 mmol/L NMDA was perfused for 2 hours. Extracellular concentrations of
      neurotransmitter and neuromodulator amino acids were measured. Untreated rats
      were compared with those given 10 mg/kg 3-aminobenzamide. RESULTS: In experiment
      1, PARP inhibition significantly reduced lesion volumes: 204+/-43 mm3 (untreated)
      versus 90+/-24 mm3 (treated). Neuroprotection was primarily manifested in the
      cortex. In experiment 2, NMDA perfusion resulted in large elevations of
      glutamate, taurine, and the lipid component phosphoethanolamine. Levels of the
      NMDA site modulator D-serine were reduced, and glycine levels appeared unchanged.
      3-Aminobenzamide significantly attenuated the elevations in glutamate and
      phosphoethanolamine but had no effects on D-serine and glycine. CONCLUSIONS:
      Inhibition of PARP reduced injury after transient focal ischemia in rats and
      attenuated NMDA-induced glutamate efflux and overall neurotransmitter
      dysregulation. The deleterious effects of excessive PARP activation may be
      related in part to amplification of excitotoxicity, possibly by cellular energy
      depletion and additional transmitter release and/or reduced reuptake.

PMID- 9550520
TI  - Potassium channel activators protect the N-methyl-D-aspartate-induced cerebral
      vascular dilation after combined hypoxia and ischemia in piglets.
AB  - BACKGROUND AND PURPOSE: Cerebral arteriolar dilation to N-methyl-D-aspartate
      (NMDA) is a neuronally mediated multistep process that is sensitive to cerebral
      hypoxia and ischemia (H/I). We tested the hypothesis that topical pretreatment
      with the selective potassium channel agonists NS1619 and aprikalim preserves the
      vascular response to NMDA after consecutive H/I. METHODS: Pial arteriolar
      diameters were measured in anesthetized piglets with the use of a closed cranial
      window and intravital microscopy. Arteriolar responses to NMDA (10(-5), 5 x 10(
      5), and 10(-4) mol/L) were recorded before and 1 hour after 10 minutes of hypoxia
      (8.5% O2 in N2) plus 10 minutes of ischemia (H/I). Ischemia was induced by
      increasing intracranial pressure. Subgroups were topically pretreated with 10(-5)
      mol/L NS1619, 10(-6) mol/L aprikalim, 10(-6) mol/L calcitonin gene-related
      peptide (CGRP), or 10(-5) mol/L papaverine. We also examined the effects of H/I
      on vascular responses to kainate (10(-4) mol/L) to assess specificity of neuronal
      injury. RESULTS: Arteriolar responses to NMDA were significantly attenuated after
      H/I. Baseline compared with post-H/I arteriolar diameters were 9+/-4% versus 3+/
      2% at 10(-5) mol/L, 22+/-4% versus 4+/-2% at 5 x 10(-5) mol/L, and 33+/-4% versus
      7+/-2% at 10(-4) mol/L (mean+/-SE; all P<.05, n=7). Pretreatment with NS1619 and
      aprikalim preserved the arteriolar responses to NMDA after H/I. For NS1619 (n=6),
      values were as follows: 9+/-2% versus 6+/-4% at 10(-5) mol/L, 19+/-6% versus 21+/
      5% at 5 x 10(-5) mol/L, and 35+/-3% versus 31+/-5% at 10(-4) mol/L. For aprikalim
      (n=7), values were as follows: 6+/-2% versus 8+/-2% at 10(-5) mol/L, 22+/-6%
      versus 15+/-3% at 5 x 10(-5) mol/L, and 41+/-5% versus 32+/-6% at 10(-4) mol/L.
      In contrast, piglets pretreated with CGRP (n=6) or papaverine (n=5) showed no
      preservation of the vascular response to NMDA after H/I, although these compounds
      dilated the arterioles to an extent similar to that with NS1619/aprikalim.
      Kainate-induced arteriolar dilation (n=6) was largely preserved after H/I
      compared with preischemic responses. CONCLUSIONS: (1) Vascular responses of
      cerebral arterioles to NMDA after H/I are preserved by pretreatment with NS1619
      or aprikalim, indicating a neuroprotective effect. (2) CGRP and papaverine do not
      preserve the vascular response to NMDA despite causing vasodilation similar to
      that with NS1619 or aprikalim. This suggests that activation of potassium
      channels on neurons accounts for the protective effect of potassium channel
      agonists. (3) Preserved arteriolar dilation to kainate suggests largely intact
      functioning of neuronal nitric oxide synthase after H/I.

PMID- 9550521
TI  - Low glucose enhances Na+/glucose transport in bovine brain artery endothelial
      cells.
AB  - BACKGROUND AND PURPOSE: Brain arteries are structurally characterized by the
      tight junctions of the endothelium and by no vasa vasorum that feed arteries
      themselves. This raises the question of how brain arteries are provided with
      glucose. A possible explanation is that glucose uptake into arteries may be
      mediated by both GLUT1, a facilitative glucose transporter, and a Na+/glucose
      cotransporter (SGLT)-like glucose transporter. The functional role for the SGLT
      like glucose transporter, however, is unknown. In the present study we
      investigated SGLT-like glucose transporter-operated glucose uptake into brain
      arterial endothelial cells by recording glucose-evoked Na+ currents and
      monitoring uptake of [3H]-2-deoxy-D-glucose ([3H]-2-DOG). METHODS: Endothelial
      cells were cultured from bovine cerebral cortical arteries. Whole-cell patches
      were made to cells, and glucose-evoked currents were recorded. Cells were
      incubated with [3H]-2-DOG, and the uptake was determined by a liquid
      scintillation counter. RESULTS: Glucose and alpha-methyl-D-glucoside (alphaMeDG),
      a specific compound for the SGLTs, evoked Na+ currents in a whole-cell voltage
      clamp configuration, and the currents were enhanced in cells with over 30
      minutes' preincubation in glucose-free media. Glucose-induced currents were
      inhibited by alphaMeDG, by the selective SGLT inhibitor phlorizin, by
      dinitrophenol (DNP), an inhibitor of energy metabolism, or by deletion of Na+
      from extracellular solution, which indicates that glucose uptake into endothelial
      cells was mediated by a Na+- and energy-dependent glucose transporter. Notably,
      the currents were desensitized, reduced in a glucose concentration-dependent
      manner, and markedly inhibited by either a second application of glucose or the
      addition of glucose to the patch electrode filling solution; they were
      potentiated, however, by treatment with cytochalasin B, a GLUT1 to GLUT5
      inhibitor. Consistent with the results of patch-clamp recordings, uptake of [3H]
      2-DOG into endothelial cells was enhanced by glucose-free insult, and the
      enhancement was mediated by an SGLT-like glucose transporter. CONCLUSIONS: The
      results presented demonstrate that an SGLT-like glucose transporter takes part in
      glucose uptake into brain artery endothelial cells and that the uptake is
      regulated by intracellular glucose concentrations; glucose-free insult and the
      ensuing low cytosolic glucose enhance activity of the SGLT-like glucose
      transporter. The SGLT-like glucose transporter in the brain arterial endothelium
      thus may be important in the maintenance of an adequate glucose concentration in
      the arterial wall under conditions of stress, such as hypoglycemia.

PMID- 9550522
TI  - A novel endothelin antagonist, A-127722, attenuates ischemic lesion size in rats
      with temporary middle cerebral artery occlusion: a diffusion and perfusion MRI
      study.
AB  - BACKGROUND AND PURPOSE: Endothelins (ETs) are potent vasoconstrictors. Plasma ET
      levels increase during acute brain ischemia and may worsen the ischemic damage.
      Diffusion-weighted MRI (DWI) and perfusion imaging (PI) are powerful tools for
      evaluation of acute cerebral ischemia. We studied the effects of A-127722, a
      novel ET(A)-selective ET antagonist, on cerebral ischemic lesion size using 2,3,5
      triphenyltetrazolium chloride (TTC) staining postmortem, on acute ischemic lesion
      development with DWI, and on the cerebral circulation using PI. METHODS: Twenty
      male Sprague-Dawley rats received either 5 mg/kg of A-127722 or vehicle (n=10 per
      group) intravenously 30 minutes and subcutaneously 4 hours after middle cerebral
      artery occlusion (MCAO). Whole-brain DWI and single-slice PI were done before
      initiation of treatment and repeated frequently thereafter up to 4 hours after
      MCAO. The animals were reperfused in the MRI scanner 90 minutes after the onset
      of MCAO. At 24 hours the animals were killed, and the brains were cut into six 2
      mm-thick slices and stained with 2% TTC. Percent hemispheric lesion volume (%HLV)
      was calculated for each animal. RESULTS: Physiological parameters, body weight,
      neurological scores, and premature mortality (2 versus 2) did not differ between
      the two groups. No hypotension, abnormal behavior, or other adverse effects were
      seen. TTC-derived %HLV was 25.3+/-5.6% for controls and 16.2+/-9.6% for treated
      animals (36% reduction, P<.02). Six animals in each group had successful
      reperfusion as shown by PI. Among these animals, %HLV was 23.2+/-3.1% for
      controls and 9.3+/-4.4% for treated animals (60% reduction, P=.0001). The
      beneficial effect of A-127722 was limited to animals in which successful
      reperfusion was demonstrated. No difference in PI-detected perfusion deficit size
      was observed between the groups. DWI did not demonstrate significant in vivo
      lesion size differences. CONCLUSIONS: A-127722 significantly reduced ischemic
      lesion size in rats without observable adverse effects. It is not clear whether
      the effect was due to vasodilatation of collateral arterioles not detectable by
      PI or whether A-127722 has neuroprotective properties that are independent of
      vascular effects.

PMID- 9550523
TI  - Different apparent diffusion coefficient: water content correlations of gray and
      white matter during early ischemia.
AB  - BACKGROUND AND PURPOSE: Early and accurate diagnosis of brain edema in stroke
      patients is essential for the selection of appropriate treatment. We examined the
      correlations between the changes in the apparent diffusion coefficient (ADC),
      regional water content, and tissue ultrastructure during early focal cerebral
      ischemia. METHODS: The left middle cerebral arteries of cats were occluded with
      an intramagnet occlusion/recirculation device. T2-weighted, diffusion-weighted,
      and perfusion imaging were performed repeatedly during the initial 3 hours after
      occlusion. The ADCs obtained from ADC maps were compared with the corresponding
      tissue water content values determined by gravimetry and electron microscopic
      water localization. RESULTS: ADC reduction was detected in areas of low perfusion
      15 minutes after occlusion and thereafter. The water content increase correlated
      linearly with the ADC decreases in both the gray and white matter. However, both
      the water content corresponding to an ADC value and the rate of ADC change of the
      gray and white matter differed significantly (P<.05) as follows: y = -10105x +
      8533 (r=.86) and y = -6174x + 4611 (r=.67), respectively, where x is the water
      content (grams water per gram tissue) and y is the ADC (x 10(-6) mm2/s). Hydropic
      astrocytic swelling was seen in both structures, and in the white matter,
      oligodendroglial and myelinated axonal swelling and periaxonal space enlargement
      were observed. CONCLUSIONS: When early ischemic edema in experimental focal
      cerebral ischemia is evaluated with ADC mapping, the different slopes and
      intercepts of the water content and ADC correlation lines for the gray and white
      matter, which probably reflect different ultrastructural localization of water,
      should be taken into account.

PMID- 9550524
TI  - Prevalence of stroke and stroke-related disability.

PMID- 9550525
TI  - Causes and mechanisms of cerebellar infarction in young patients.

PMID- 9550526
TI  - Hypertension control as an indicator of the geographical variation of stroke.

PMID- 9550527
TI  - Autoimmunity in Down's syndrome: another possible mechanism of Moyamoya disease.

PMID- 9550528
TI  - Homozygous C677T mutation of the 5,10 methylenetetrahydrofolate reductase gene
      and hyperhomocysteinemia in Italian patients with a history of early-onset
      ischemic stroke.

PMID- 9550529
TI  - Interrater agreement on a simple neurological score in rats.

PMID- 9550530
TI  - The Working Group report on Science-Based Categories for Abstracts: submitted to
      the annual scientific sessions. The Committee on Scientific Sessions Program
      (CSSP), American Heart Association.

PMID- 9550531
TI  - Serum lipids during the first year following acute spinal cord injury.
AB  - Patients with chronic spinal cord injury (SCI) have low levels of high-density
      lipoprotein (HDL) cholesterol. The cause of this abnormality and its relation to
      SCI are unknown. We studied 100 consecutively admitted males with acute SCI
      prospectively for 1 year to determine changes in serum lipids following acute SCI
      and the relation of these changes to the level of injury and physical activity.
      Low-density lipoprotein (LDL), HDL, and total cholesterol and triglycerides were
      all decreased following acute SCI and gradually increased toward normal by 1
      year. Serum HDL, LDL, and total cholesterol levels correlated with the level of
      SCI: levels were lower in quadriplegic compared with paraplegic patients. Serum
      HDL showed the greatest change following SCI, increasing by 26% in quadriplegic
      and 18% in paraplegic patients. These changes in serum lipid levels could not be
      explained by changes in alcohol consumption or body weight. We estimated that
      only 44% of the increase in HDL following SCI was associated with an increase in
      physical activity. We postulate that interruption of the autonomic nervous system
      influences lipid metabolism and serum lipid levels.

PMID- 9550532
TI  - The effects of menopausal status and exercise training on serum lipids and the
      activities of intravascular enzymes related to lipid transport.
AB  - The study purpose was to compare the effect of exercise training on serum lipid
      and apolipoprotein concentrations and the activities of intravascular enzymes
      related to lipid transport in previously untrained eumenorrheic, premenopausal
      (PRM) women (n = 21; mean age, 36 +/- 3 years) and estrogen-free postmenopausal
      (POM) women (n = 16; mean age, 68 +/- 8 years). Subjects trained at a progressive
      intensity and duration (50% to 75% maximal O2 consumption [VO2max], 200 to 300
      kcal/session) 4 d/wk for 12 weeks. Before and after training, VO2max, body
      weight, relative body fat, and fasting blood samples were obtained following 2
      weeks on a standardized diet designed to maintain body weight and during the
      early follicular stage for the PRM group. Blood samples were analyzed for serum
      total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol
      (HDL-C), the cholesterol content of the HDL3 subfraction, apolipoprotein (apo)A-I
      and apoB, lipoprotein(a), and the activity of lecithin:cholesterol
      acyltransferase (LCAT). Total and hepatic triglyceride lipase activity (HTGLA)
      were determined from plasma samples obtained after heparin administration. The
      cholesterol content of the low-density lipoprotein (LDL) and HDL2 subfractions
      and endothelial-bound lipoprotein lipase activity (LPLA) were calculated. A two
      (group) x two (time) multivariate ANOVA (MANOVA), with repeated measures for time
      indicated that the exercise-induced changes in physiological measurements, serum
      lipid or apolipoprotein concentrations, or enzyme activities did not differ
      between groups. Serum concentrations of TC, LDL-C, and HDL3 cholesterol, TG, and
      apo A-I and apoB were higher in POM women compared with the PRM group (P < .05
      for all). For the combined groups, body weight and relative body fat did not
      change with training, but VO2max increased an average of 18.5% (P < .05). LPLA,
      HTGLA, and LCAT activity were unaltered with exercise training. Except for a
      small but significant decrease in HDL-C (-5.5%) and an elevation in apoB (4.3%; P
      < .05 for both), the concentrations of serum lipids and apolipoproteins did not
      change over the training period. We conclude that in previously untrained women,
      menopausal status does not influence the exercise training response of serum
      lipids or apolipoproteins or activities of intravascular enzymes related to lipid
      transport.

PMID- 9550533
TI  - Intense nonpharmacological intervention in subjects with multiple cardiovascular
      risk factors: decreased fasting insulin levels but only a minor effect on plasma
      plasminogen activator inhibitor activity.
AB  - Increased plasma levels of insulin and the fibrinolytic inhibitor, plasminogen
      activator inhibitor type 1 (PAI-1), are two new cardiovascular risk factors. The
      extent to which these two risk factors can be affected by nonpharmacological
      intervention modalities has not been convincingly proven in subjects at high risk
      for cardiovascular disease. This study assesses the effects on fasting plasma
      insulin and plasma PAI-1 activity of an intervention program including a low-fat,
      high-fiber diet and regular daily physical exercise. The intervention was
      implemented by a 1-month learning and training session in a full-boarding
      wellness center and included a follow-up evaluation after 12 months. The study
      was conducted on 108 subjects (31 men and 77 women) referred for multiple risk
      factor treatment. After 1 month of intense intervention, the physical condition
      improved significantly, and this effect was maintained during the year. The body
      mass index (BMI), fasting plasma insulin, and plasma lipids were significantly
      decreased. In women, PAI-1 activity was significantly reduced. At follow-up study
      in both sexes, the BMI and fasting insulin were still significantly decreased. In
      women, PAI-1 activity reverted to the preintervention level. In subjects with
      multiple risk factors, ie, the insulin resistance syndrome, the plasma insulin
      level can be reduced by an intense nonpharmacological program. Also, at least in
      women, plasma PAI-1 activity can be modestly modified. However, the magnitude of
      the decrease in PAI-1 activity was probably too small to reverse the
      hypofibrinolytic state characteristic of these subjects.

PMID- 9550535
TI  - Dietary chromium decreases insulin resistance in rats fed a high-fat, mineral
      imbalanced diet.
AB  - The effects of chromium (Cr) supplementation on diet-induced insulin resistance
      produced by feeding a high-fat, low-Cr diet were studied in rats to ascertain the
      role of Cr in insulin resistance. Wistar male rats were maintained for 16 weeks
      after weaning on a basal diet containing 40% lard, 30% sucrose, and 25% casein by
      weight and adequate vitamins and minerals without added Cr (-Cr). Fasting levels
      of insulin, glucose, and triglycerides and the responses during an intravenous
      glucose tolerance test (IVGTT) were compared as indices of insulin resistance and
      the effectiveness of dietary Cr. IVGTTs and blood sampling for data analyses were
      performed over a 40-minute period after IV glucose injection (1.25 g/kg body
      weight) in overnight-fasted animals under pentobarbital anesthesia (40 mg/kg body
      weight). All animals were normoglycemic (-Cr, 109 +/- 3 mg/dL; +Cr, 119 +/- 5),
      with fasting insulin levels elevated in the -Cr group (65 +/- 10 microU/mL)
      versus the +Cr group (31 +/- 4 microU/mL). Increases in plasma triglycerides in
      the -Cr group were not significant. Following glucose injection, the rate of
      glucose clearance was lower in the -Cr group (1.74 +/- 0.22 v2.39 +/- 0.11%/min),
      and 40-minute glucose areas in the -Cr group tended to be higher than in the +Cr
      group. The insulin response to glucose injection was 20% higher in the -Cr group.
      Forty-minute plasma triglyceride areas were lower in +Cr rats (875 +/- 62 v 1,143
      +/- 97 mg/dL.min in -Cr rats). These data demonstrate that the insulin resistance
      induced by feeding a high-fat, nutrient-stressed diet is improved by Cr.

PMID- 9550534
TI  - Sex steroids increase cholesterol 7alpha-hydroxylase mRNA in nonhuman primates.
AB  - One mechanism that may account for our prior observation that oral contraceptives
      decrease the hepatic cholesterol concentration independently of the low-density
      lipoprotein (LDL) receptor in sexually intact nonhuman primates is that sex
      hormones increase biliary cholesterol secretion by increasing hepatic mRNA
      abundance for cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in the
      conversion of cholesterol into bile acids. To examine the independent effect of
      estrogen, progestin, and combined estrogen and progestin on the hepatic
      cholesterol concentration and cholesterol 7alpha-hydroxylase mRNA abundance, 34
      ovariectomized adult female cynomolgus monkeys were fed a moderately atherogenic
      diet for 12 weeks with either oral conjugated equine estrogen ([CEE] n = 8),
      medroxyprogesterone acetate ([MPA] n = 9), or combined CEE + MPA (n = 9) and
      compared with a control group (n = 8) that did not receive exogenous sex
      hormones. After 12 weeks, hepatic cholesterol was significantly lower in CEE
      treated (6.2 +/- 1.2 mg/g liver) and CEE + MPA-treated (6.4 +/- 0.9 mg/g liver)
      animals compared with the control (12.6 +/- 1.9 mg/g liver) and MPA-treated (14.6
      +/- 1.6 mg/g liver) groups. Hepatic cholesterol 7alpha-hydroxylase mRNA abundance
      was significantly increased in CEE-treated (0.553 +/- 0.08 pg/microg RNA), MPA
      treated (0.734 +/- 0.12 pg/microg RNA), and CEE + MPA-treated (0.487 +/- 0.07
      pg/microg RNA) animals compared with the controls (0.318 +/- 0.03 pg/microg RNA).
      There was no significant difference in the plasma LDL cholesterol concentration
      and hepatic LDL receptor mRNA abundance between the groups. These data support
      but do not prove the hypothesis that low-dose oral estrogen induces an increase
      in cholesterol 7alpha-hydroxylase mRNA abundance, which is correlated with
      biliary cholesterol secretion and may result in depletion of hepatic cholesterol.

PMID- 9550536
TI  - Insulin resistance and fat patterning with aging: relationship to metabolic risk
      factors for cardiovascular disease.
AB  - Both insulin resistance and abdominal fat patterning are related to aging, and
      have been related to cardiovascular disease (CVD) risk factors such as
      dyslipidemia and hypertension. However, previous studies have not used direct
      methods to quantify the independent strength of the association of each of these
      two putative primary factors with metabolic outcomes. We quantified overall
      obesity by the body mass index (BMI) and used a previously validated magnetic
      resonance imaging (MRI) method to quantify abdominal fat in 63 healthy
      nondiabetic individuals aged 22 to 83 years. We also measured the glucose and
      insulin response to an oral glucose tolerance test and the insulin sensitivity
      ([SI] by modified minimal model analysis). Body fat patterning was evaluated by
      the waist to hip ratio (WHR) and by MRI, which allowed direct measurement of
      subcutaneous (SCF) and intraabdominal (IAF) fat depots at the umbilicus in these
      subjects. These independent parameters were related to risk factors for CVD
      (blood pressure, lipids, and lipoproteins) and to plasma concentrations of free
      fatty acids (FFAs). Measures of overall obesity (BMI), total fat [TF], and/or SCF
      measured at the abdomen by MRI), glucose/insulin metabolism and SI, and central
      fat patterning (WHR or IAF measured by MRI) were correlated with mean arterial
      pressure (MAP), triglyceride (TG), and high-density lipoprotein cholesterol (HDL
      C) levels in univariate analysis and after controlling for age and gender. An
      index of central fat patterning (WHR) added to the informativeness of the insulin
      area under the curve (IAUC) in explaining 24% of the variability in plasma TG
      concentration, but measures of overall obesity were not independently related.
      Both the BMI and TF contributed to the IAUC in explaining 32% to 34% of the
      variability in MAP, but central fat patterning was not independently related. No
      index of overall obesity, fat patterning, glucose/insulin metabolism, and/or SI,
      was independently related to the plasma concentration of HDL-C after controlling
      for any one of the other two. Direct measurement of glucose/insulin metabolism
      and SI, as well as fat patterning, provides information on their relative
      associations with CVD risk factors. The measures of glucose/insulin metabolism
      and SI were more consistently related to dyslipidemia and hypertension than were
      the overall obesity and fat patterning in this healthy population.

PMID- 9550537
TI  - In vivo quantification of glucose uptake and conversion to glycogen in individual
      muscles of the rat following exercise.
AB  - Glycogen depletion is thought to be a potent stimulus for the substantially
      increased glucose fluxes observed in skeletal muscle following exercise. The aim
      of this study was to establish the relationships between the glycogen mass and
      the rates of glucose uptake (Rg') and glucose incorporation into glycogen (Rgly)
      in individual muscles of conscious adult Wistar rats following moderate
      nonexhausting treadmill exercise (15 m/min at a 10 degree slope for 45 minutes,
      approximately 65% VO2max). Muscle glycogen content was determined at 0, 20, 45,
      90, or 135 minutes following exercise and compared with Rg' and Rgly measurements
      at matched times. Muscle types varied in the rate of glycogen resynthesis.
      Glycogen depots of glycolytic muscle (white gastrocnemius) were still
      significantly (P < .01) lower than preexercise levels after 135 minutes; red
      oxidative muscles (soleus and red gastrocnemius) were essentially repleted by 90
      minutes. Immediately following exercise, Rg' and Rgly in red gastrocnemius and
      soleus were 42 +/- 4 and 42 +/- 5 and 36 +/- 2 and 33 +/- 7 micromol/(min . 100
      g), greater than the rates induced by maximal insulin stimulation in previous
      studies. In red muscles, there was a strong inverse relationship between Rgly and
      tissue glycogen content, consistent with a dominant role for the glycogen mass in
      the regulation of glycogen resynthesis.

PMID- 9550538
TI  - Alterations in rat pancreatic islet beta cells induced by Keshan disease
      pathogenic factors: protective action of selenium and vitamin E.
AB  - Keshan disease (KD) is an endemic cardiomyopathy occurring in certain areas of
      China. A combined deficiency of selenium (Se) and vitamin E (VE) has been
      implicated in the development of KD. In this study, morphological and functional
      alterations in the islet beta cells of rats fed grain from an endemic area with
      KD were investigated. Serum insulin levels and glutathione peroxidase (GSH-Px)
      activity were markedly lower in rats on the experimental diet compared with
      controls. In pancreatic islet beta cells of rats on the experimental diet, a
      vacuolation of the Golgi apparatus, slight dilation of the endoplasmic reticulum,
      and decrease in the number of secretory granules were seen. Supplementation of
      either 100 mg/kg VE (alpha-tocopherol) and/or 0.1 mg/kg Se (as 0.22 mg/kg sodium
      selenite) to the experimental diet prevented these islet beta-cell alterations
      and returned serum insulin to normal levels. Our results demonstrate that the
      pathogenic factors of KD can induce alterations in islet beta cells, and Se and
      VE provide protective effects against these pathogenic factors.

PMID- 9550539
TI  - Association of fasting insulin with serum lipids and blood pressure in Kuwaiti
      children.
AB  - To examine the association of hyperinsulinemia with the atherogenic risk profile
      in children, we studied the relationships of the fasting plasma insulin level
      with indices of obesity (body mass index [BMI] and sum of triceps and subscapular
      skinfold thickness [SFT]), body fat distribution (waist to hip ratio [WHR]),
      serum lipid, lipoprotein, and apolipoprotein levels, and blood pressure in a case
      control study of 460 Kuwaiti prepubertal obese children aged 6 to 13 years
      matched by age and sex to 460 prepubertal non-obese controls. Obese children were
      ascertained in a representative cross-sectional study of 2,400 school children.
      Fasting insulin levels were positively correlated (P < .001) with serum
      triglyceride (TG) and very-low-density lipoprotein (VLDL) cholesterol levels and
      negatively correlated with high-density lipoprotein (HDL) cholesterol levels. No
      significant associations were observed between insulin and total cholesterol
      (TC), cholesterol, low-density lipoprotein (LDL) or apolipoprotein A-I (apo A-I).
      Stronger associations of insulin levels with lipoprotein fractions were observed
      in obese versus non-obese controls. Obese children had a higher concentration of
      apo B and a lower apo A-I:B ratio (P < .001). Insulin and the insulin to glucose
      ratio increased with age in obese children, whereas there were slight changes in
      non-obese children. TG and HDL cholesterol levels and systolic blood pressure
      (SBP) were significantly different across insulin quartiles in boys and girls. We
      conclude that the fasting plasma insulin level may be used as a marker for the
      development of obesity-associated metabolic disorders and elevated blood pressure
      in children.

PMID- 9550540
TI  - Relative effects of prolactin excess and estrogen deficiency on bone in rats.
AB  - Humans with prolactinoma are at risk for osteoporosis. The relative contributions
      of hyperprolactinemia-induced hypogonadism and the prolactin (PRL) excess per se
      have been unclear from clinical studies. To determine the effects of PRL excess,
      two models of chronic hyperprolactinemia were used. In one, mild
      hyperprolactinemia was produced in rats bearing extra anterior pituitary glands
      under the kidney capsule. Severe hyperprolactinemia was produced by
      subcutaneously transplanting the PRL-secreting MMQ tumor into other rats. To
      control for estrogen deficiency, the rats were ovariectomized. In some
      experiments, estrogen replacement was provided. Urinary calcium excretion was
      increased in hyperprolactinemic rats compared with controls, regardless of
      severity of PRL excess and estrogen status. This suggested that PRL excess itself
      had some effect on calcium balance. More importantly, however, the spinal bone
      mineral density (BMD; measured by dual-energy x-ray densitometry) of mildly
      hyperprolactinemic ovariectomized rats was the same as control ovariectomized
      rats. Similarly, tibial dry weight and ash weight were affected by the estrogen
      status, but not by the severe PRL excess of the tumor-implanted rats. Thus,
      despite the evidence for an increase in urinary calcium excretion in
      hyperprolactinemic rats, estrogen deficiency is much more important in
      determining bone mineral. Therefore, the present data indicate that the
      osteoporosis of hyperprolactinemia is likely due to PRL-induced hypogonadism,
      rather than a direct effect of PRL on calcium homeostatis.

PMID- 9550542
TI  - The effect of menopause on serum uric acid levels in non-obese healthy women.
AB  - Elevated circulating serum uric acid concentrations may be linked with an
      increased risk of coronary heart disease (CHD). We measured serum uric acid
      levels in 50 premenopausal and 88 postmenopausal non-obese white women who
      underwent an intravenous glucose tolerance test. The uric acid concentration was
      significantly higher in postmenopausal versus premenopausal women. Adjustment of
      the data to take into account a number of confounding variables, including the
      age and body mass index (BMI), revealed a highly significant independent
      difference between the groups. BMI was found to be a significant independent
      predictor of the uric acid concentration, but this was confined to premenopausal
      women. Postmenopausal women were found to be more insulin-resistant, and
      significant correlations were observed between components of the insulin
      resistance syndrome and uric acid in both groups. We conclude that increases in
      serum acid in postmenopausal women may result from changes in metabolism as a
      consequence of the menopause, and may be associated with the increased risk of
      CHD seen in these women.

PMID- 9550541
TI  - Changes of serum leptin and endocrine and metabolic parameters after 7 days of
      energy restriction in men and women.
AB  - Circulating leptin decreases during fasting in rodents and humans; however, the
      mechanism of the decrease is unknown. The aim of this study was to examine the
      relationship between decrements of serum leptin concentrations and changes of
      hormonal (insulin and cortisol) and metabolic (glucose, ketones, and fatty acids)
      parameters involved in the metabolic adaptation to energy restriction in normal
      weight humans. Because there are marked gender differences in circulating leptin,
      both men and women were studied. The body mass index (BMI), percent body fat (%
      body fat), and serum leptin, insulin, cortisol, glucose, beta
      hydroxybutyrate,(BOHB), and nonesterified fatty acids (NEFA) were determined in
      11 men and 13 women (age, 20 to 41 years; BMI, 21.2 to 26.8 kg/m2) before and
      during 7 days of energy restriction (-68% +/- 1% of daily energy requirements).
      Weight loss averaged about 4% in both men and women. Leptin in men was 3.7 +/-
      0.5 and decreased to 2.1 +/- 0.4 ng/mL (percent change [%delta], -36% +/- 6.0%, P
      < .0005) during restriction. Concurrently, insulin decreased from 7.2 +/- 0.6 to
      1.8 +/- 0.3 microU/mL (%delta, -74% +/- 4%, P < .0001). In contrast, leptin was
      higher in women before (16.2 +/- 1.9 ng/mL) and after (6.0 +/- 0.8 ng/mL)
      restriction and decreased more than in men (%delta, -61% +/- 4%, P < .02 v men),
      whereas the decrease of insulin in women was less than in men: 10.1 +/- 1.9 to
      6.1 +/- 1.0 microU/mL (%delta, -31% +/- 9%, P < .0025; P < .0005 v men), perhaps
      because glucose decreased less in women than in men. Overall, the changes of
      leptin during fasting were independently correlated with the changes of glucose
      (r = .53, P < .007), NEFA (r = .53, P < .01), and BOHB (r = .65, P < .001). In
      addition, the change of leptin correlated with a combined index of the parameters
      that reflect decreased glucose availability and increased lipolysis
      ([deltaglucose + deltainsulin + deltaNEFA]/3, r = .73, P < .0001) or a combined
      index of parameters that would be expected to limit glucose uptake by adipocytes
      ([deltaglucose + deltainsulin + deltacortisol]/3, r = .48, P < .02). We conclude
      that there are significant differences between men and women in the responses of
      leptin and insulin to energy restriction. Furthermore, decreases of circulating
      leptin during negative energy balance are related to changes of endocrine and
      metabolic parameters, suggesting that leptin secretion may be regulated by
      alterations of adipocyte glucose and lipid metabolism, ie, decreased glucose
      uptake and metabolism and increased lipolysis.

PMID- 9550543
TI  - Effect of beta-adrenoceptor blockade on postexercise oxygen consumption and
      triglyceride/fatty acid cycling.
AB  - In the recovery period after strenuous exercise, there is increased O2 uptake,
      termed the excess postexercise O2 consumption (EPOC). One of the mechanisms
      suggested to explain EPOC is activation of the triglyceride/fatty acid (TG/FA)
      cycle by catecholamines. The purpose of this study was to determine the effect of
      selective beta1- and nonselective beta-adrenoceptor blockade on EPOC and the
      TG/FA cycle. Seven healthy young men each participated in three control and three
      exercise experiments in a randomized and balanced sequence. In the exercise
      experiments, subjects exercised for 90 minutes at 58% +/- 2% (mean +/- SD) of
      maximal O2 uptake on a cycle ergometer, followed by a 4.5-hour bedrest. The
      control experiments followed the same protocol, but without exercise. In one
      control and one exercise experiment, the selective beta1-adrenoceptor antagonist
      atenolol (0.062 mg.kg(-1) body weight) was administered intravenously immediately
      after the exercise (EXAT) and at the corresponding time in the rest-control
      experiment (REAT). In a second set of control and exercise experiments, the
      nonselective beta-adrenoceptor antagonist propranolol (0.15 mg.kg(-1) body
      weight) was administered (REPRO and EXPRO). In a third set of rest and exercise
      experiments, an injection of saline was given instead of beta-antagonist (RE and
      EX). TG/FA cycling was calculated by combining results obtained with a two-stage
      glycerol infusion and indirect calorimetry. O2 uptake was significantly increased
      above control levels throughout the recovery period after exercise with the
      nonselective beta-adrenoceptor antagonist, beta1-adrenoceptor antagonist, and
      saline. However, there was no difference between the time course or magnitude of
      EPOC in the three situations. After 4.5 hours of bedrest, the mean increase in O2
      uptake was 8% to 9% in all three conditions. TG/FA cycling was increased after
      exercise, but no effects of beta-antagonists were observed. We conclude that EPOC
      and the rate of TG/FA cycling are not attenuated by selective beta1- or
      nonselective beta-adrenoceptor blockade after an acute prolonged exercise
      protocol.

PMID- 9550544
TI  - Insulin and glucosamine infusions increase O-linked N-acetyl-glucosamine in
      skeletal muscle proteins in vivo.
AB  - O-linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational
      modification of serine/threonine residues of nuclear and cytoplasmic proteins. We
      determined whether insulin or coinfusion of glucosamine (GlcN) with insulin
      alters O-GlcNAc of skeletal muscle proteins. Three groups of conscious fasted
      rats received 6-hour infusions of either saline (BAS), insulin 18 mU/kg.min and
      saline (INS), or insulin and GlcN 30 micromol/kg.min (GLCN) during maintenance of
      normoglycemia. At 6 hours, the concentrations of muscle UDP-GlcNAc, UDP-N
      acetylgalactosamine (UDP-GalNAc), UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal),
      glycogen, and N and O-linked GlcNAc (galactosyltransferase labeling followed by
      beta elimination) were measured in freeze-clamped abdominis muscle. Insulin
      increased whole-body glucose uptake from 49 +/- 5 to 239 +/- 8 micromol/kg.min (P
      < .001) and glycogen in abdominis muscle from 138 +/- 11 to 370 +/- 26 mmol/kg
      dry weight (P < .001). Insulin increased the amount of cytosolic N - and O-linked
      GlcNAc by 56% from 362 +/- 30 to 564 +/- 45 dpm/microg protein . 100 min (P <
      .02), and O-GlcNAc from 221 +/- 16 to 339 +/- 27 dpm/microg . 100 min (P < .02).
      Glycogen content was positively correlated with the amount of total (r = .90, P <
      .005) and O-linked GlcNAc in insulin-infused animals. Coinfusion of GlcN with
      insulin increased muscle UDP-GlcNAc about fourfold (100 +/- 6 nmol/g) compared
      with insulin (27 +/- 1, P < .001) or saline (25 +/- 1, P < .001) infusion. GlcN
      also decreased glucose uptake over 6 hours by 30% to 168 +/- 8 micromol/kg . min
      (P < .001 for GLCN v INS) and muscle glycogen to 292 +/- 24 mmol/kg dry weight (P
      < .05 for GLCN v INS). Both total (635 +/- 60 dpm/microg . 100 min, P < .002) and
      O-linked GlcNAc (375 +/- 36 dpm/microg . 100 min, P < .002) in the cytosol were
      significantly higher in GLCN rats (635 +/- 60 dpm/microg) versus BAS rats (P <
      .002). As in INS rats, muscle glycogen and O-GlcNAc were positively correlated in
      GLCN rats (r = .54, P < .05). Variation in total and O-linked GlcNAc in GLCN rats
      was due both to GlcN (P < .02) and to variation in the glycogen content (P <
      .005).

PMID- 9550545
TI  - The significance of the Trp 64 Arg mutation of the beta3-adrenergic receptor gene
      in impaired glucose tolerance, non-insulin-dependent diabetes mellitus, and
      insulin resistance in Japanese subjects.
AB  - It has been reported that the Trp 64 Arg mutation of the human beta3-adrenergic
      receptor (beta3-AR) gene is related to an earlier age of onset of non-insulin
      dependent diabetes mellitus (NIDDM) and features of insulin resistance and weight
      gain in morbidly obese patients. However, such findings have not been consistent
      in varying ethnic populations. In the present study, we investigated the
      frequency of the Trp 64 Arg mutation of the human beta3-AR gene in Japanese
      control subjects (n = 253) and in NIDDM (n = 314) and impaired glucose tolerance
      (IGT) patients (n = 100). We compared the frequency of the mutation with the body
      mass index (BMI) in these groups and with the metabolic clearance rate (MCR) of
      glucose in the NIDDM patients. A Trp 64 Arg mutation was observed in 36.7%,
      31.6%, and 37.0% of the control, NIDDM, and IGT subjects, respectively. The
      frequency of the homozygotes for the mutation was 4.3%, 4.8%, and 3.0%,
      respectively. Neither the genotype frequency (Trp/Arg, Arg/Arg) nor the frequency
      of the mutated allele was significantly different among the three groups. The BMI
      of the subjects with the mutation was not significantly higher than that of the
      subjects without the mutation in each group. Furthermore, the allele frequency
      (A) was not different among the subjects with different BMIs (BMI < 22.0, 22.0 <
      or = BMI < or = 26.4, BMI > 26.4) in each group. In a separate group of NIDDM
      patients, the MCR of the subjects with intermediate BMIs (22.0 < or = BMI < or =
      26.4) with the mutation tended to be lower than that of those without the
      mutation. In addition, the MCR of the subjects with the mutation in this group
      was significantly lower compared with that of those with a BMI less than 22.
      These results indicate that the Trp 64 Arg mutation of the beta3-AR gene may not
      contribute to the development of NIDDM or be a determinant of obesity in the
      Japanese population. However, the mutation may contribute to insulin resistance
      in NIDDM patients with an intermediate BMI.

PMID- 9550546
TI  - Arachidonic acid metabolites of the lipoxygenase as well as the cyclooxygenase
      pathway may be involved in regulating preadipocyte differentiation.
AB  - Conditions that trigger preadipocyte differentiation in vivo have yet to be
      elucidated. To investigate the role of endogenous arachidonic acid (AA)
      metabolites on adipose tissue growth, rat preadipocytes in primary culture were
      induced to differentiate using medium conditioned by isolated mature adipocytes
      (ACM). Differentiation was determined by assay of glycerol-3-phosphate
      dehydrogenase (GPDH). When collected in the presence of indomethacin (10 nmol/L)
      to inhibit prostaglandin (PG) synthesis by adipocytes, ACM induced greater
      differentiation (GPDH activity, 405 +/- 68 nmol NADH used/min/mg protein) than
      when indomethacin was added postcollection to inhibit preadipocyte PG synthesis
      (205 +/- 24, P < .05) or ACM alone (304 +/- 55). This suggested that PGs released
      by adipocytes inhibited differentiation, whereas those released by preadipocytes
      appeared to act in an autocrine manner to stimulate differentiation. However, 24
      hour collections of ACM contained 125 pmol/L PGE2 and 900 pmol/L PGI2,
      concentrations too low to promote differentiation when added exogenously.
      Nordihydroguaiaretic acid (NDGA; 10 pmol/L), an inhibitor of lipoxygenase (LOX),
      stimulated the ACM-induced increase in GPDH activity (ACM, 99 +/- 13; ACM + NDGA,
      369 +/- 130). In contrast, when differentiation was induced by a hormonal
      cocktail (MIX), including insulin and corticosterone, NDGA decreased GPDH
      activity (MIX, 329 +/- 66; MIX + NDGA, 142 +/- 40; P < .03). We concluded that
      preadipocyte differentiation within adipose tissue may be subject to both
      positive and negative regulators derived from AA metabolism resulting from both
      LOX and cyclooxygenase (COX) activity.

PMID- 9550547
TI  - Regional differences in adrenoceptor binding and fat cell lipolysis in obese,
      postmenopausal women.
AB  - In women there is an increase in visceral obesity, subcutaneous abdominal
      adipocyte lipolysis, and risk of cardiovascular disease (CVD) associated with
      weight gain after menopause. The mechanisms underlying this increase in
      adrenoreceptor (AR)-agonist catecholamine-stimulated lipolysis and abdominal
      obesity in postmenopausal women were studied in intact adipocytes isolated from
      the abdominal and gluteal subcutaneous fat depots in 19 obese (48% +/- 1% body
      fat, mean +/- SE) women with a mean +/- SE age of 58 +/- 1 years. The fat cell
      size and adipose tissue lipoprotein lipase (ATLPL) activity were similar in both
      sites. The maximal lipolytic responsiveness and sensitivity to isoproterenol were
      higher (P < .05) in abdominal compared with gluteal adipocytes, but maximal
      lipolytic response to a post-AR agent was similar. Abdominal adipocytes had a
      higher beta-AR ([3H]-CGP-12177) and alpha2-AR ([3H]-yohimbine) affinity than
      gluteal cells (P < .05), lower alpha2-AR density (P < .05), but similar beta-AR
      density as gluteal cells. Both abdominal and gluteal cell size correlated with
      alpha2-AR density (P < .01), but not with beta-AR density. Thus, a higher beta-AR
      affinity and lower alpha2-AR relative to beta-AR density may explain the higher
      in vitro catecholamine-mediated lipolysis in abdominal compared with gluteal
      adipocytes in obese, postmenopausal women.

PMID- 9550548
TI  - Effects of thyroid hormone (thyroxine) and testosterone on hepatic 11beta
      hydroxysteroid dehydrogenase mRNA and activity in pubertal hypothyroid male rats.
AB  - To investigate the effects of thyroid hormone and testosterone on 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1), we measured changes in hepatic
      11beta-dehydrogenase activity and its mRNA levels in pubertal methimazole (MMI)
      induced hypothyroid male rats following treatment with thyroxine ([T4] 50
      microg/kg/d) or testosterone (250 microg/d) for 14 days. Hypothyroidism in male
      rats markedly reduced hepatic 11beta-HSD1 mRNA levels and serum testosterone
      concentrations (P < .01). Subcutaneous injection of T4 in the hypothyroid rats
      significantly (P < .01) increased hepatic 11beta-HSD1 mRNA to approximately
      normal levels and simultaneously increased serum testosterone levels. However,
      the same daily dose of T4 administered to castrated male hypothyroid rats for 14
      days did not elevate hepatic 11beta-HSD1 activity. Treatment with testosterone
      for 14 days in castrated hypothyroid male rats and rats without gonadectomy
      significantly (P < .01) increased the enzyme activity without administration of
      T4. Variations in hepatic 11beta-HSD1 activity were demonstrated to be
      accompanied by changes in serum testosterone levels in the rats following
      alteration of the thyroid hormone state. These results suggest that the effect of
      T4 in increasing the subnormal 11beta-HSD1 gene expression in hypothyroid male
      rats is mediated by its ability to increase testosterone production in these
      rats, because in castrated hypothyroid rats, T4 does not elevate 11beta-HSD1 gene
      expression.

PMID- 9550549
TI  - Low-density lipoprotein-apolipoprotein B metabolism following apheresis:
      simulation studies of mass changes and tracer kinetics.
AB  - Low-density lipoprotein (LDL) apheresis is an effective method to treat severe
      hyperlipoproteinemia such as heterozygous familial hypercholesterolemia (FH). It
      is unknown whether apheresis induces changes in metabolic parameters of LDL
      apolipoprotein B (apoB) such as the fractional catabolic rate (FCR) or production
      rate. We performed simulation studies to determine the effect of potential
      changes in the LDL FCR on LDL-apoB mass and on exogenous and endogenous tracer
      studies. For these studies, we assumed a two-compartment LDL model and the
      following metabolic parameters: plasma LDL-apoB, 180 mg.dL(-1); LDL-apoB
      production rate, 36 mg.dL(-1).d(-1) (approximately 14.4 mg.kg(-1).d(-1)); and LDL
      apo FCR, 0.2 d(-1). It was also assumed that apheresis instantaneously decreased
      the LDL-apoB concentration to 60 mg.dL(-1) and that LDL-apoB production was not
      perturbed. The simulations examined three possible outcomes: (1) no change in
      FCR, (2) a temporary doubling in FCR, and (3) a temporary tripling in FCR.
      Monoexponential models were fit to the rebound of LDL-apoB mass data generated
      using the different FCRs. In no instance did the FCR determined from the fit
      match the FCR used to generate the data; FCRs were either higher or lower than
      the original FCR used to generate the data. Simulations of the kinetics of
      exogenously labeled LDL showed that if apheresis was performed on day 7 of a
      turnover study, it would be possible to detect large changes in LDL-apoB FCR. In
      contrast, during an endogenous labeling study, potential increases in FCR induced
      by apheresis may not be detected. However, our simulations do show that
      endogenous labeling studies performed before and after apheresis should yield
      data that will permit detection of changes in the FCR. Thus, these studies
      indicate that large differences in the LDL-apoB FCR induced by apheresis can be
      detected by either an exogenous tracer experiment perturbed by apheresis or by
      endogenous labeling experiments performed before and after apheresis. Small
      changes in the FCR that may be induced by apheresis will probably be
      indistinguishable from experimental noise.

PMID- 9550550
TI  - SAAM II: Simulation, Analysis, and Modeling Software for tracer and
      pharmacokinetic studies.
AB  - Kinetic analysis and integrated systems modeling have contributed substantially
      to our understanding of the physiology and pathophysiology of metabolic systems
      and the distribution and clearance of drugs in humans and animals. In recent
      years, many researchers have become aware of the usefulness of these techniques
      in the experimental design. With this has come the recognition that the
      discipline of kinetic analysis requires its own expertise. The expertise can
      impact experimental design in many ways, from the collaborative and service
      activities in which individuals interact in formal ways to the development of
      software tools to aid in kinetic analysis. The purpose of this report is to
      describe one such software tool, Simulation, Analysis, and Modeling Software II
      (SAAM II). In the first part, we describe in general how the user can take
      advantage of the capabilities of the software system, and in the second part, we
      give three specific examples using multicompartmental models found in lipoprotein
      (apolipoprotein B [apoB] kinetics) and diabetes (glucose minimal model) research.

PMID- 9550551
TI  - Circulating transferrin receptor assay--coming of age.

PMID- 9550553
TI  - Fundamentals of quality assessment of molecular amplification methods in clinical
      diagnostics. International Federation of Clinical Chemistry Scientific Division
      Committee on Molecular Biology Techniques.
AB  - The increasing interest in molecular biology diagnostics is a result of the
      tremendous gain of scientific knowledge in genetics, made possible especially
      since the introduction of amplification techniques. High expectations have been
      placed on genetic testing, and the number of laboratories now using the relevant
      technology is rapidly increasing--resulting in an obvious need for
      standardization and definition of laboratory organization. This communication is
      an effort towards that end. We address aspects that should be considered when
      structuring a new molecular diagnostic laboratory, and we discuss individual
      preanalytical and analytical procedures, from sampling to evaluation of assay
      results. In addition, different means of controlling contamination are discussed.
      Because the methodology is in constant change, no general standards can be
      defined. Accordingly, this publication is intended to serve as a recommendation
      for good laboratory practice and internal quality control and as a guide to
      troubleshooting, primarily in amplification techniques.

PMID- 9550552
TI  - Molecular diagnosis of medium-chain acyl-CoA dehydrogenase deficiency by
      oligonucleotide ligation assay.

PMID- 9550554
TI  - Validation by isoelectric focusing of the anion-exchange isotransferrin
      fractionation step involved in determination of carbohydrate-deficient
      transferrin by the CDTect assay.
AB  - Serum concentration of carbohydrate-deficient transferrin (CDT) is used for
      laboratory diagnosis of chronic alcohol abuse. Using isoelectric focusing for
      validation of the initial isotransferrin fractionation step involved in the
      determination of CDT by the CDTect assay, we found a complete in vitro iron
      saturation of transferrin and sufficient stability of the transferrin iron load
      during column passage; effective separation of non-CDT-isotransferrins and CDT
      isotransferrins at the microcolumns; partial coelution of trisialo-Fe2
      transferrin, which did not significantly affect CDT measurement; partial
      retention of CDT-isotransferrins, especially disialo-Fe2-transferrin, which may
      cause falsely negative results for CDT at the upper reference limits; good
      precision of the isotransferrin fractionation step; and no significant effects of
      low concentrations of serum protein and transferrin. We strongly urge
      standardization of CDT analysis and suggest isoelectric focusing for validation
      of CDT analysis methods and verification of odd results.

PMID- 9550555
TI  - Measurement of soluble transferrin receptor in serum of healthy adults.
AB  - The concentration of soluble transferrin receptor (sTfR) in serum is reported to
      be useful in the diagnosis of iron deficiency, especially for patients with
      concurrent chronic disease, where routine tests of iron status are compromised by
      the inflammatory condition. A new diagnostic assay for sTfR is calibrated against
      natural plasma sTfR, thus minimizing calibration discrepancies that result from
      differences between the analyte and the cellular transferrin receptor used in
      other assays. Use of the new assay to measure sTfR concentrations in 225 healthy,
      hematologically normal adults provided a reference interval against which
      pathological samples could be compared. There was no difference in the reference
      intervals for men and women and no correlation of [sTfR] with the age of the
      subject. Black subjects had significantly higher concentrations than nonblacks,
      and people living at high altitude had higher concentrations than those living
      closer to sea level. These differences were additive.

PMID- 9550556
TI  - Serum transferrin receptors are decreased in the presence of iron overload.
AB  - To test the hypothesis that the quantities of circulating transferrin receptors
      are reduced in iron overload, we studied serum transferrin receptors and indirect
      measures of iron status in 150 subjects from rural Zimbabwe. We found significant
      inverse correlations between serum concentrations of transferrin receptors and
      ferritin, the ratio of ferritin to aspartate aminotransferase, and transferrin
      saturation (r > or = 0.44; P < 0.001). The mean +/- SD concentration of serum
      transferrin receptors in 23 subjects classified as having iron overload (ferritin
      > 300 microg/L and transferrin saturation > 60%) was 1.55 +/- 0.61 mg/L,
      significantly lower than the 2.50 +/- 0.62 mg/L in 75 subjects with normal iron
      stores (ferritin 20-300 microg/L and transferrin saturation 15-55%; P < 0.0005)
      and the 2.83 +/- 1.14 mg/L in 8 subjects with iron deficiency (ferritin < 20
      microg/L; P = 0.001). In keeping with the regulation of transferrin receptor
      expression at the cellular level, our findings suggest that serum transferrin
      receptors are decreased in the presence of iron overload.

PMID- 9550557
TI  - Clinical utility of the soluble transferrin receptor and comparison with serum
      ferritin in several populations.
AB  - Soluble transferrin receptor (sTfR) and ferritin concentrations were measured in
      a variety of clinical settings to compare the ability of these two tests to
      identify iron deficiency. Among 62 anemic patients who either had a bone marrow
      aspirate performed or had a documented response to iron therapy, the diagnostic
      sensitivity and specificity of sTfR (at a diagnostic cutoff of > 2.8 mg/L) were
      92% and 84%, respectively, with a positive predictive value of 42% in this
      population. Ferritin (< or = 12 microg/L) had a sensitivity of 25% and a
      specificity of 98%. However, the sensitivity and specificity of ferritin could be
      improved to 92% and 98%, respectively, by using a diagnostic cutoff value of < or
      = 30 microg/L, resulting in a positive predictive value of 92%. Ferritin and sTfR
      were also measured in 267 outpatient samples and 112 medical students. In the
      outpatient group, the two tests agreed in 73% of the samples; however, 25% of the
      samples had ferritin values > 12 microg/L and increased sTfR. Among the medical
      students, there was 91% agreement between the two tests, but 7% of the samples
      had ferritin < or = 12 microg/L and normal sTfR. Together, these data suggest
      that measurement of sTfR does not provide sufficient additional information to
      ferritin to warrant routine use. However, sTfR may be useful as an adjunct in the
      evaluation of anemic patients, whose ferritin values may be increased as the
      result of an acute-phase reaction.

PMID- 9550558
TI  - Cardiac troponin I measurement with the ACCESS immunoassay system: analytical and
      clinical performance characteristics.
AB  - We evaluated the ACCESS cardiac troponin I (cTnI) immunoassay as a marker for
      myocardial infarction (MI). Total imprecision was 6.0% to 13.5%, the minimum
      detectable concentration was 0.007 microg/L, and the limit of quantitation was
      0.046 microg/L. Comparison of cTnI measurement between the ACCESS and Stratus
      systems (n = 114) showed a proportional difference: ACCESS cTnI = 0.0996 Stratus
      cTnI + 0.049 microg/L (r = 0.811). Fifty-nine of 61 ambulatory patients without
      cardiac symptoms had no detectable cTnI (95% range, 0.00 to 0.025 microg/L). The
      optimum cutoff for discriminating MI (n = 289, 45 with MI) was 0.15 microg/L by
      receiver operator characteristic curve analysis; at this cutoff, the ACCESS cTnI
      assay showed a sensitivity of 88.9% (95% CI, 79.7-98.1%) and specificity of 91.8%
      (95% CI, 88.4-95.2%). The ACCESS cTnI assay results showed 89.4% and 93.0%
      concordance with the MB isoenzyme of creatine kinase (CK-MB) mass and Stratus
      cTnI results, respectively, for classification of patients with suspected MI. The
      ACCESS cTnI assay appears to show sensitivity and specificity comparable with
      those of both CK-MB mass and Stratus cTnI assays for the diagnosis of MI in
      patients presenting within 12 h of onset of symptoms.

PMID- 9550559
TI  - X-chromosome inactivation in healthy females: incidence of excessive lyonization
      with age and comparison of assays involving DNA methylation and transcript
      polymorphisms.
AB  - Skewed lyonization in healthy females represents the major disadvantage of X
      chromosome-based clonality assays. Because most techniques are based on the
      difference in DNA methylation between active and inactive X-chromosomes,
      incomplete DNA digestion may occur, giving an unreliable clonality result. Here,
      we compare two different techniques carried out in healthy females belonging to
      three age groups and in a group of patients with essential thrombocythemia. The
      first technique involved the human androgen receptor gene, the second the
      transcript analysis of the iduronate-2-sulfatase, P55, and glucose-6-phospate
      dehydrogenase genes. Results between both techniques were concordant in most
      cases except in neonates, and the same pattern was observed in all fractions in
      healthy females. We conclude that: (a) clonality assays involving DNA and RNA
      polymorphisms are usually concordant except in neonates; (b) appropriate control
      tissue embryologically related to the sample must be chosen to eliminate
      excessive lyonization; (c) acquired skewing increases with age, whereas nonrandom
      lyonization is a rare phenomenon.

PMID- 9550560
TI  - Molecular diagnosis of medium-chain acyl-CoA dehydrogenase deficiency by
      oligonucleotide ligation assay.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a recessively inherited
      defect in the mitochondrial beta-oxidation of fatty acids. A single nucleotide
      change, the A985 --> G transition, in the MCAD gene accounts for approximately
      90% of all the disease-causing mutations in the patients. We have used PCR to
      amplify a segment of the human MCAD gene and typed the allelic sequence variation
      at base 985 by a colorimetric oligonucleotide ligation assay (OLA). PCR/OLA
      provides a technique that permits differentiation of the homozygotes,
      heterozygotes, and normals for the A985 --> G allele in the MCAD gene. Genotyping
      of 1908 random Finnish DNA samples by OLA identified 10 carriers of the mutant
      allele, but no homozygotes were found. The calculated carrier frequency for the
      A985 --> G mutation was 1:191 (95% confidence limits, 1:118-1:501), and the
      calculated frequency for the A985 --> G homozygotes was 1:147,000 (95% confidence
      limits, 1:56,000-1:1,004,000).

PMID- 9550561
TI  - Exon 5 of the p53 gene is a target for deletions in ovarian cancer.
AB  - Missense point mutations, leading to inactivation of the p53 tumor suppressor
      gene product, are currently the most frequent alterations in human cancer.
      Little, however, is known about small intragenic deletions or insertions
      occurring in this locus of chromosome 17. We have analyzed 56 primary ovarian
      tumors for the presence of such abnormalities. The analysis was based on
      multiplex PCR amplification of exons 1 through 11 of the p53 gene and fragment
      analysis of the generated PCR products. Mutations were detected in 14% (8 of 56)
      of the tumors. Deletions were much more prevalent than insertions (seven vs one).
      Six of the deletions and the insertion affected exon 5, and the other deletion
      was in exon 7. Two deletions and the insertion did not disrupt the reading frame;
      the protein product was expressed in the tumor at high concentrations in all
      three cases. The other five deletions generated a frameshift, which is predicted
      to result in the production of a truncated protein product. In the case of the
      deletions, a 2-5-bp repeat was present close to the detected deletion, whereas
      the insertion duplicated the sequence immediately upstream of the insertion site.
      Overall our findings indicate that small intragenic p53 deletions/insertions are
      not rare events in ovarian cancer, and that p53 exon 5 is the target in the vast
      majority (88%) of the cases.

PMID- 9550562
TI  - Immunoradiometric assay of succinylated corticotropin: an improved method for
      quantification of ACTH.
AB  - In this paper we describe the development and the evaluation of a new type of
      immunoassay for human corticotropin (ACTH). We succeeded, by using an original
      approach based upon immunization with ACTH derivatized with succinic anhydride,
      in raising monoclonal antibodies against this poorly immunogenic peptide. Three
      of the antibodies were selected to develop an immunoassay for ACTH. The assay
      requires the prior succinylation of the plasma samples for optimal sensitivity
      and specificity. This acylation treatment is fast, reproducible, and, in
      addition, improves the stability of the ACTH molecule in plasma, thus
      facilitating sample handling. The assay is performed in only 3 h with a detection
      limit of 0.7 ng/L. Analytical evaluation showed excellent specificity,
      reproducibility, and reliability. A comparison with two commonly used but time
      consuming ACTH IRMAs was carried out by assaying several plasma samples in
      parallel and gave in both cases very good correlation.

PMID- 9550563
TI  - Rapid, automated assay for progesterone on the Abbott AxSYM analyzer.
AB  - We describe an automated assay for progesterone (P4) in human serum and plasma
      with the Abbott AxSYM random-access immunoassay analyzer. In this one-step
      competitive assay, P4 immobilized onto latex microparticles competes with sample
      P4 for binding to a conjugate of alkaline phosphatase (AP) and anti-P4 antibody.
      Total CVs ranged from 3.4% to 8.2% in multiple precision studies conducted
      according to the 20-day NCCLS EP5-T protocol. The detection limit (zero
      calibrator + 2 SD) was 0.10 microg/L across 36 experiments. Values for diluted
      samples were 83-116% of expected. Recovery of P4 added to serum specimens was 92
      115%. Cross-reactivities with 43 natural and synthetic steroids were 0-6.3%. No
      significant interference was detected from bilirubin, protein, erythrocytes,
      hemoglobin, triglycerides, or cholesterol. In a multisite correlation study,
      AxSYM P4 results compared well with results from a commercial RIA method (n =
      1156; r = 0.976; slope = 1.03; y-intercept = 0.04). Assay throughput is >80 tests
      per hour in batch mode, 60 tests per hour with mixed load list configurations.

PMID- 9550564
TI  - Evaluation of the Sysmex UF-100 automated urinalysis analyzer.
AB  - Urinalysis is a high-volume procedure that currently requires significant labor
      to examine microscopic sediment. We evaluated the Sysmex UF-100 automated
      urinalysis analyzer for performing this task. Instrument accuracy was assessed by
      comparing continuous counts of microscopic elements from the UF-100 with ranges
      of cells (per low-power field or high-power field) from manual microscopy
      performed on centrifuged urines. Counts showed good agreement between methods
      (gamma statistic: 0.880-0.970) for all microscopic elements in 252 urine samples.
      Within-run imprecision of cell counts expressed as CV (mean cell count/microL)
      was for erythrocytes (RBC) 31% (5), 18% (50), 2.4% (800); for leukocytes (WBC)
      14% (10), 11% (100), 8.5% (400); for squamous epithelial cells (SEC) 18% (5), 12%
      (30), 7.0% (100); for casts 45% (1), 17% (4); for bacteria 2-12% (entire range of
      40-2500). Between-run imprecision on quality-control cell suspensions expressed
      as CV (mean cell count/microL) was for RBC 6.1% (50), 2.7% (256); for WBC 26.9%
      (54), 4.9% (228). Cells counted on dilution were 99.1% of expected for RBC,
      102.0% for WBC, and 121.8% for bacteria. Carryover was <0.04% for RBC, <0.03% for
      WBC, <0.14% for SEC, <0.29% for bacteria. We conclude that the UF-100 can
      automatically perform reliable quantitative microscopic urinalysis in batches
      without operator interaction.

PMID- 9550565
TI  - Hematological indices in an older population sample: derivation of healthy
      reference values.
AB  - Factors affecting hematological values were explored, and healthy reference
      values were estimated from a cross-sectional survey of a population (n = 4433),
      ages 49 years or more, residing permanently in a defined geographic region.
      Nursing home residents were excluded. Details of medication use and medical
      history were obtained by interview, and participants were asked to return after
      an overnight fast for blood sampling. The participation rate was 82.4%, of whom
      88.4% provided a fasting blood sample. Hemoglobin, hematocrit, and erythrocyte
      counts were higher in men, whereas platelet counts were higher in women.
      Statistical associations between each hematological index and smoking, alcohol
      intake, use of certain drugs, chronic disease, and high creatinine values were
      tested by unpaired t-tests. Separate reference groups were defined for each
      hematological index by excluding subjects with any of the factors found to be of
      importance. The resulting reference values are particularly appropriate for
      evaluating hematological test results in older individuals.

PMID- 9550566
TI  - Variability and determinants of total homocysteine concentrations in plasma in an
      elderly population.
AB  - The variability of plasma total homocysteine (tHcy) was examined in 96
      individuals over a 1-yr period. Blood tHcy concentrations varied from 7.1
      micromol/L in the bottom quintile to 14.5 micromol/L in the top quintile. The
      mean tHcy was 10.4 micromol/L, the between-person SD was 2.5 micromol/L, and the
      within-person SD was 0.93 micromol/L. There was little seasonal variation, and
      the reliability coefficient was 0.88. Mean tHcy concentrations were inversely
      related to mean plasma folate (r = -0.36) and vitamin B12 (r = -0.35)
      concentrations. Median tHcy concentrations were approximately 1 micromol/L higher
      in men than in women and in older (70 to 74 years) than in younger (65 to 69
      years) individuals and higher in those with the TT and CT genotypes for the
      methylenetetrahydrofolate reductase polymorphism than in those with the CC
      genotype (10.7 and 10.6 vs 9.6 micromol/L). Epidemiological studies based on
      single tHcy measurements may underestimate the magnitude of any risk associations
      with disease by 10-15%.

PMID- 9550567
TI  - Quantifying the bias associated with use of discrepant analysis.
AB  - Discrepant analysis is a widely used technique for estimating the performance
      parameters of a laboratory test. In discrepant analysis, each specimen is
      initially tested with the candidate test and a comparison method, and when the
      results of the two tests disagree, a confirmatory test is used to resolve the
      discrepancy. Discrepant analysis usually produces biased estimates. This report
      quantifies this bias and shows that it is usually positive, leading to
      overestimation of the performance parameters of a laboratory test. The direction
      and magnitude of the bias are predictably influenced by the analytical
      sensitivity and specificity of the candidate test, comparison method, and
      confirmatory test. The proportion of abnormal specimens tested also affects the
      magnitude of the bias, particularly the estimates of analytical sensitivity and
      positive predictive value when this proportion is low. Alternative approaches are
      suggested.

PMID- 9550568
TI  - Statistically accurate estimation of hormone concentrations and associated
      uncertainties: methodology, validation, and applications.
AB  - We describe a data reduction procedure to assign statistically accurate estimates
      of unknown hormone concentrations, with associated uncertainties, based on
      experimental uncertainties in sample replicates and the fitted calibration curve.
      Three mathematical calibration curve functions are considered. The one providing
      optimal statistical characterization of reference calibrators is chosen for
      unknown evaluation. Experimental error is addressed by assigning and propagating
      uncertainty estimates for each measured response (including zero-dose responses)
      by an empirically determined discrete uncertainty profile and by propagating
      calibration curve uncertainty. Discrete uncertainty profiles account for both
      response precision (replicability) and accuracy (deviation from predicted
      calibration curves) without relying on assumed theoretical response variance
      assay response relations. The validity of assigning variable response weighting
      by this procedure was assessed by Monte Carlo simulations based on
      chemiluminescence growth hormone calibration curves. Much-improved accuracy and
      estimated precision are achieved for unknown hormone concentrations, particularly
      extremely low concentrations, by using this variable response weighting
      procedure.

PMID- 9550569
TI  - Proficiency testing of creatine kinase and creatine kinase-2: the experience of
      the Ontario Laboratory Proficiency Testing Program.
AB  - The Ontario Laboratory Proficiency Testing Program has regularly monitored the
      analytical performance of total creatine kinase (CK) (approximately 230
      participants) and CK isoenzyme-2 (CK-MB) (approximately 160 participants)
      throughout the entire province. Consistently, a wide dispersion of results has
      been observed not only between different analyzer systems but also among
      identical analyzers. Accordingly, the results of the last three proficiency
      surveys for these analytes were examined statistically to establish both the
      extent of these variations and the range of values reported for the male upper
      reference ranges. The results of many of the analyzer systems were significantly
      different from each other, as were many of the reference ranges. This
      unsatisfactory situation may only be remedied by the use of reference materials
      as shown by others. The consequences of these findings also effect the
      reliability of epidemiological surveys such as the WHO MONICA Project
      (Circulation 1994;90:583-612), which monitors deaths due to heart disease and
      includes cardiac enzyme results in its criteria.

PMID- 9550570
TI  - Plasma apolipoproteins A-I and B in survivors of myocardial infarction and in a
      control group.
AB  - The values of apolipoproteins (apo) A-I and B were determined in a population
      sample of hospital outpatients with a standardized method to verify if the
      cutpoints calculated in a cross-sectional study in the US are usable with other
      populations. We also tested the apolipoproteins' ability to discriminate between
      healthy people and survivors of myocardial infarction. In the studied population
      the apo A-I value corresponding to the HDL-cholesterol decisional centile is 1.12
      g/L for males and 1.17 g/L for females; the apo B value corresponding to the LDL
      cholesterol decisional centile is 1.23 g/L for males and 1.14 g/L for females.
      These values are quite close to the cutpoints proposed for the American
      population (1.20 g/L for both apolipoproteins). In comparison with the LDL- and
      HDL-cholesterol decisional concentrations, the cutpoints for apolipoproteins
      allow a correct classification of a greater percentage of postmyocardial
      infarction patients (16% higher for apo B and 5% for apo A-I). Standardized
      assays coupled with a reference database allow a better clinical use of
      apolipoprotein measurements.

PMID- 9550571
TI  - Study of arsenic-protein binding in serum of patients on continuous ambulatory
      peritoneal dialysis.
AB  - Arsenic (As) bound to serum proteins in patients on continuous ambulatory
      peritoneal dialysis (CAPD) was studied. A prior experiment by ultrafiltration
      showed that 5.57% of total As was bound to serum proteins for 14 CAPD patients.
      Further identification of the As species and protein molecules in serum of three
      CAPD patients with high As concentrations was carried out by combining the
      separation methods of size-exclusion, anion-exchange, and affinity fast-protein
      liquid chromatography, detected by hydride generation atomic absorption
      spectrometry. The results indicated that only inorganic As species are bound to
      serum proteins. Transferrin is the main carrier. The concentrations of As bound
      to proteins in serum for the three patients were 0.44 +/- 0.12, 0.19 +/- 0.09,
      and 0.59 +/- 0.09 microg/L (n = 3), respectively.

PMID- 9550572
TI  - Increased oxidative stress in dilated cardiomyopathic heart failure.
AB  - In the present study, we assessed oxidative stress in patients with dilated
      cardiomyopathy of ischemic or idiopathic etiology. For this reason we measured
      whole blood reduced glutathione, erythrocyte superoxide dismutase, susceptibility
      of erythrocyte membranes and erythrocytes to peroxidation, and SH content of
      erythrocyte membranes in 12 patients (8 men and 4 women, ages 31 to 66 years)
      with idiopathic dilated cardiomyopathy, in 11 patients (8 men and 3 women, ages
      32 to 65 years) with ischemic dilated cardiomyopathy, and in 21 healthy
      volunteers (12 men and 9 women, ages 25 to 67 years). There was no statistically
      significant difference between the two patient groups for the indicators studied
      (P >0.05). Blood glutathione, erythrocyte superoxide dismutase, and membrane SH
      content of both groups of patients was decreased compared with controls (P
      <0.05), whereas erythrocyte and membrane susceptibility to peroxidation were
      increased (P <0.05). We conclude that patients with idiopathic or ischemic
      dilated cardiomyopathy exhibit abnormalities of a range of markers of increased
      oxidative stress. These abnormalities may contribute to contractile dysfunction,
      increased incidence of fatal arrhythmias, and sudden death.

PMID- 9550573
TI  - Mechanisms of dopamine and dobutamine interference in biochemical tests that use
      peroxide and peroxidase to generate chromophore.
AB  - Dopamine and dobutamine have recently been shown to produce a negative
      interference in several biochemical tests that use peroxide and peroxidase to
      generate a chromophore. To define the chemical mechanism of this interference, we
      examined the effects of dopamine and dobutamine in various peroxidase-based
      biochemical tests. Dopamine interfered stoichiometrically with peroxidase-based
      tests that use 4-aminophenazone to form chromophore but interfered little in
      those that use other compounds to generate chromophore. Dopamine reacts with 4
      aminophenazone in the presence of peroxide and peroxidase to form a novel quinone
      imine dye, with a smaller absorptivity than the chromophore formed in the absence
      of dopamine. The smaller absorptivity of this novel chromophore results in
      negative interference by reducing the total absorbance at the wavelength used to
      measure analyte. In contrast, dobutamine interfered stoichiometrically with all
      peroxidase-based tests studied, regardless of whether 4-aminophenazone was used
      to form the chromophore. Dobutamine was rapidly oxidized by peroxide in the
      presence of peroxidase, thus depleting the peroxide necessary to generate
      chromophore. Dopamine and dobutamine demonstrate two distinct general mechanisms
      of interference in peroxidase-based biochemical tests.

PMID- 9550574
TI  - Neopterin concentrations in cerebrospinal fluid and serum as an aid in
      differentiating central nervous system and peripheral infections in children.
AB  - Neopterin is a sensitive indicator for cellular immune activation. Its
      concentrations were determined in cerebrospinal fluid (CSF) and serum specimens
      from 91 children with no evidence of central nervous system (CNS) or peripheral
      inflammations, 43 with definite neuroborreliosis, 51 with other CNS infections,
      and 33 with peripheral infections. The aim of our study was (a) to establish a
      range of normal CSF neopterin concentrations in control children, and (b) to
      inquire into the diagnostic potential of neopterin measurements in both body
      compartments for aiding in differential diagnosis of inflammatory vs
      noninflammatory diseases, and CNS vs peripheral inflammations. CSF neopterin
      concentrations in controls were invariably low (up to 9.3 nmol/L), but in
      children with neuroborreliosis and, even more so, with other CNS infections
      neopterin concentrations were significantly (P <0.0001) increased. Children with
      peripheral infections, however, rarely showed raised CSF neopterin
      concentrations. Serum concentrations of neopterin, on the other hand, were not
      significantly different between controls and children with neuroborreliosis.
      Although serum concentrations were significantly different between controls and
      children with other CNS infections, diagnostic efficiency was poor for this
      comparison. Peripheral infections, in contrast, were associated with
      significantly higher (P <0.0001) serum neopterin concentrations when compared
      with controls. A classification tree was constructed on the basis of CSF and
      serum neopterin concentrations, allowing with high accuracy the discrimination
      between controls, children with CNS infections, and children with peripheral
      infections. Thus, on the basis of a comparatively large control group, our data
      underline the diagnostic validity of neopterin as an aid in differential
      diagnosis of inflammatory vs noninflammatory diseases, and confirm that CSF
      neopterin concentrations are not correlated with serum neopterin concentrations,
      and, therefore, CSF neopterin appears to be produced intrathecally.

PMID- 9550575
TI  - Ethylene glycol poisoning: toxicokinetic and analytical factors affecting
      laboratory diagnosis.
AB  - Ethylene glycol poisoning is an important toxicological problem in medical
      practice because early diagnosis and treatment can prevent considerable morbidity
      and mortality. When ingested in the form of antifreeze or other automotive
      products, ethylene glycol results in central nervous system depression,
      cardiopulmonary compromise, and renal insufficiency. Metabolism of ethylene
      glycol to organic acids is required for metabolic derangement and organ damage.
      Laboratory features of ethylene glycol poisoning include increased anion gap
      metabolic acidosis, increased osmolal gap, calcium oxalate crystalluria, and
      detectable ethylene glycol in serum. This Case Conference integrates discussion
      of the toxicokinetic and analytical variables that affect the laboratory
      diagnosis of ethylene glycol intoxication.

PMID- 9550576
TI  - Direct molecular interaction of phenylalanine with DNA measured by reversed-phase
      HPLC.

PMID- 9550577
TI  - Serum paraoxonase and platelet-activating factor acetylhydrolase in chronic renal
      failure.

PMID- 9550578
TI  - High concentrations of prostate-specific antigen in urine of women receiving oral
      contraceptives.

PMID- 9550579
TI  - CpG-PCR combined with sample pooling and mutant enrichment for CpG mutation
      screening in population studies.

PMID- 9550580
TI  - When is an indole not an indole?

PMID- 9550581
TI  - Whole-blood folate values in subjects with different methylenetetrahydrofolate
      reductase genotypes: differences between the radioassay and microbiological
      assays.

PMID- 9550582
TI  - Simplified simultaneous assay of total plasma homocysteine and methionine by HPLC
      and pulsed integrated amperometry.

PMID- 9550583
TI  - The Sia euglobulin precipitation test revisited.

PMID- 9550584
TI  - Analytical characteristics of seminal fluid PSA differ from those of serum PSA.

PMID- 9550585
TI  - Human beings, nature and medicine: perspectives of internal medicine.

PMID- 9550586
TI  - Informed consent in Japan.

PMID- 9550587
TI  - Familial hemiplegic migraine.

PMID- 9550588
TI  - Sjogren's syndrome and sarcoidosis.

PMID- 9550589
TI  - The treatment of heart failure: the role of neurohumoral activation.
AB  - Neurohumoral activation refers to increased activity of the sympathetic nervous
      system, renin-angiotensin system, vasopressin and atrial natriuretic peptide. It
      is now known that neurohumoral activation contributes to the transition from
      ventricular dysfunction to clinical heart failure, and is an independent
      predictor of poor prognosis in heart failure. Although the treatment of heart
      failure has traditionally focused on drugs to improve ventricular function, there
      is increasing evidence that therapeutic modulation of neurohumoral activation is
      a key to successful treatment of heart failure. For example, there is mounting
      evidence that angiotensin converting enzyme inhibitors (the unquestioned
      cornerstone for treatment of heart failure), beta receptor blockers, digitalis,
      and endurance exercise training exert their benefit in heart failure in large
      part through neurohumoral modulation. This observation--discussed in this brief
      review--highlights the concept that compensatory neurohumoral activation to
      decreased cardiac function may itself contribute to the development of heart
      failure and its poor prognosis.

PMID- 9550590
TI  - Relationship among risk factors of atherosclerosis, leukocyte count, and soluble
      intercellular adhesion molecule-1.
AB  - We investigated the effects of risk factors of atherosclerosis on soluble
      intercellular adhesion molecule-1 (sICAM-1) concentration and leukocyte count by
      using multivariate statistical analysis. The subjects were 90 people who were
      hospitalized for a complete check-up examination. Eight risk factors were
      selected as candidates for predictor variables: age, body mass index (BMI), uric
      acid, glycohemoglobin A1c, number of cigarettes smoked daily, total cholesterol,
      triglyceride, and high density lipoprotein (HDL)-cholesterol. The predictor
      variables were selected using a stepwise method, [criterion variable - predictor
      variable (standardized regression coefficient)]; sICAM1 - age (0.1859), number of
      cigarettes (0.2558), triglyceride (0.2447); leukocytes - number of cigarettes
      (0.2827), triglyceride (0.2526), HDL-cholesterol (-0.2800); stab leukocytes -
      number of cigarettes (0.2460); segmented leukocytes - glycohemoglobin A1c
      (0.1495), number of cigarettes (0.2716), HDL-cholesterol (-0.3254); lymphocytes -
      BMI (0.2639), number of cigarettes (0.1495), triglyceride (0.3520); monocytes -
      glycohemoglobin A1c (0.2617). These findings indicated that the risk factors of
      atherosclerosis may influence sICAM1 concentration and leukocyte count.

PMID- 9550591
TI  - Compensatory excretion of prostacyclin and thromboxane metabolites in obstructive
      sleep apnea syndrome.
AB  - Since obstructive sleep apnea syndrome (OSAS) is often linked with systemic
      hypertension, we sought to clarify the characteristics of prostanoid metabolism
      in OSAS. In 7 OSAS patients (apnea-hypopnea index, 51.0 +/- 23.4) and 7 non
      snorers as control, nocturnal urine was sampled and analyzed for stable
      metabolites of prostacyclin (PGI2) and thromboxane A2 (TxA2), [6-keto-PGF1alpha
      and thromboxane B2 (TxB2)]. The ratio of 6-keto-PGF1alpha to TxB2 was
      significantly higher in OSAS (2.97 +/- 1.52) than in control (1.38 +/- 0.38).
      Successful treatment with nasal continuous positive airway pressure (8.3 +/- 1.5
      cmH2O) for 3 days caused a significant decrease in mean blood pressure in OSAS.
      Moreover, the 6-keto-PGF1alpha to TxB2 ratio also significantly decreased to 1.74
      +/- 0.58, a level which may not significantly different from control. These
      results suggest that the production ratio of PGI2 to TxA2 is shifted toward
      vasodilatation in untreated OSAS. We conclude that the production of prostanoids
      plays a role in compensating for the systemic hypertension in OSAS.

PMID- 9550592
TI  - Control of upper airway function in response to hypoxia in patients with
      obstructive sleep apnea syndrome.
AB  - To clarify the characteristics of upper airway muscles under hypoxic condition in
      obstructive sleep apnea syndrome (OSAS), we performed the isocapnic progressive
      hypoxia test during wakefulness in 8 controls and 7 OSAS patients.
      Electromyographic activities were recorded from the genioglossal muscle (EMG(GG))
      and diaphragm (EMG(DIA)) with ventilatory variables. Minute EMG (peak integrated
      EMG x respiratory rate) activity against P(ET)O2 was calculated by exponential
      equation, and its response slope represented the hypoxic sensitivity of each
      muscle, slope(GG) and slope(DIA). There was no significant difference between the
      slopes of OSAS and control. In contrast, the ratio of the two responses,
      slope(GG)/slope(DIA), was significantly higher in OSAS (1.61 +/- 0.49 SD) than in
      control (0.98 +/- 0.43). Moreover, the slope(GG)/slope(DIA) ratio was negatively
      correlated with the ratio of sleep time with SpO2 lower than 90% to total sleep
      time. We conclude that the neuromuscular compensatory mechanism of upper airway
      muscles is effectively developed and plays an important role in preventing
      nocturnal hypoxemia in OSAS.

PMID- 9550593
TI  - Differences in clinical features and computed tomographic findings between
      embolic and non-embolic acute ischemic stroke: a quantitative differential
      diagnosis.
AB  - A diagnosis based on the presumed mechanism of stroke onset is useful for
      management strategies in acute ischemic stroke. Ninety-two patients with embolic
      (cardiac or artery-to-artery) and 107 with non-embolic (thrombotic or
      hemodynamic) stroke were diagnosed on strict cerebral angiographic criteria
      alone. To clearly discriminate between these two groups, the neurological and
      computed tomographic (CT) findings were then compared. Rapidity of onset,
      vomiting, urinary incontinence, level of consciousness, cervical bruit,
      anisocoria, tongue deviation, sensory disturbance, and CT findings (location of
      hypodense area, findings of brain edema and hemorrhagic transformation) were
      discriminatory factors between the two groups (p<0.01). According to these 11
      items, we prepared a numerical table for quantitative differential diagnosis. A
      diagnostic accuracy of 98.9% for embolic and 87.9% for non-embolic stroke in
      internal verification, and 90.0% and 82.9%, respectively, in external
      verification was observed. The differences in clinical features and CT findings
      between embolic and non-embolic stroke may reflect the pathophysiological
      mechanisms of the occlusive process of cerebral artery as well as the extent and
      severity of ischemia.

PMID- 9550594
TI  - Induction of torsades de pointes by dobutamine infusion in a patient with
      idiopathic long QT syndrome.
AB  - We used a provocative test with dobutamine infusion to diagnose long QT syndrome
      (LQTS) in a girl with a history of syncope. When dobutamine was infused at a rate
      of 10 microg/kg/min, the QT interval corrected for heart rate (QTc) was prolonged
      from 460 ms to 620 ms with abnormal TU complexes and torsades de pointes
      developed. In 5 control subjects the QTc did not change significantly during low
      dose dobutamine infusion. Low-dose dobutamine, in addition to isoproterenol, may
      be useful for evaluation of prolongation of the QT interval and abnormal TU
      complexes in patients in whom LQTS is suspected.

PMID- 9550595
TI  - Legionnaires' disease diagnosed by bronchoalveolar lavage.
AB  - A 51-year-old woman who had been on steroid therapy for systemic lupus
      erythematosus (SLE) developed a high fever 3 days after visiting a hot spring
      resort. Chest X-ray films revealed an interstitial, pneumonia-like shadow in the
      left lung field, which increased rapidly with a worsening of her symptoms. She
      died of multiple organ failure one week after the onset of the pneumonia.
      Although the serum antibody titer was negative, Legionella pneumophila was
      recovered from her bronchoalveolar lavage (BAL) fluid. BAL seems to be a useful
      method to diagnose Legionnaires' disease.

PMID- 9550596
TI  - Systemic sarcoidosis with significant granulomatous swelling of the pharyngeal
      tonsil.
AB  - A pharyngeal tonsil biopsy specimen from a 27-year-old male revealed epithelioid
      cell granulomas with noncaseating necrosis. Systemic enlargement of the lymph
      nodes was present. Plain chest radiographic and computed tomography (CT) images
      showed ground-glass attenuation in the lungs and bilateral hilar lymphadenopathy.
      Biopsy of inguinal region nodes confirmed the diagnosis of systemic sarcoidosis.
      Detailed examination of the nasopharynx should be performed in any case
      presenting with systemic sarcoidosis because the specimen is readily removable
      and the pathologic findings of the local lesion may support the diagnosis.

PMID- 9550597
TI  - Cervical spinal epidural abscess following acupuncture: successful treatment with
      antibiotics.
AB  - A 67-year-old man with poorly controlled diabetes mellitus (DM) had acupuncture
      several times a month for chronic shoulder muscle stiffness. A few days after
      acupuncture in the posterior nuchal region, a low-grade fever and backache
      developed, and subacutely progressed. Finally he complained of gait disturbance,
      and then respiratory distress appeared. Magnetic resonance imaging (MRI)
      demonstrated high cervical epidural abscess with massive soft tissue inflammation
      and vertebral osteomyelitis. Conservative treatment with antibiotics was
      effective and it was well documented by following serial MRIs. This case
      suggested that needle acupuncture should be avoided for immunocompromised
      subjects such as patients with poorly controlled DM.

PMID- 9550598
TI  - Familial hemiplegic migraine with irreversible brain damage.
AB  - Familial hemiplegic migraine (FHM) is an autosomal dominant syndrome
      characterized by recurrent episodes of varying degrees of hemiparesis associated
      with migraine. The aura including hemiparesis may be prolonged and in severe
      attacks may often be associated with confusion or coma. We describe a case of FHM
      whose aura was atypically prolonged and resulted in irreversible brain deficit
      which on magnetic resonance imaging (MRI) was suggestive of cortical
      hyperperfusion. A subsequent MRI showed left brain atrophy.

PMID- 9550599
TI  - Rhabdomyolysis after infection and taking a cold medicine in a patient who was
      susceptible to malignant hyperthermia.
AB  - A case of rhabdomyolysis after a possible viral infection and the use of a cold
      medication is reported. A 41-year-old man who presented with dysarthria,
      dysphagia, progressive weakness of his muscles and a high grade fever was
      admitted. He suffered from massive rhabdomyolysis, acute renal failure, and
      bronchopneumonia. Hemodialysis, antibiotics, and hydration therapy were effective
      in the treatment of his illness. Although the cause of the rhabdomyolysis was not
      completely clear, he was subsequently shown to be susceptible to malignant
      hyperthermia (MH) based on the results of a caffeine-halothane contracture test.
      When a mild recurrence occurred during a follow-up muscle biopsy, intravenous
      dantrolene sodium was administered and he improved immediately. This case
      suggests that MH should be considered in patients with rhabdomyolysis when the
      cause is unclear. The caffeine-halothane contracture test may also be helpful in
      the diagnosis.

PMID- 9550600
TI  - Primary Sjogren's syndrome complicated by sarcoidosis.
AB  - Sjogren's syndrome and sarcoidosis share several common features, such as
      keratoconjunctivitis sicca, swelling of parotid glands, lung involvement,
      cutaneous anergy, T cell-mediated immunodeficiency, an increased CD4+/CD8+
      lymphocyte ratio, and association with the human leucocyte antigen (HLA)-B 8 and
      DR 3 haplotypes. However, only five patients with primary Sjogren's syndrome and
      sarcoidosis have been previously reported in the English language literature. The
      rare case of a 49-year-old Japanese woman with primary Sjogren's syndrome
      complicated by sarcoidosis is described. The serum angiotensin-converting enzyme
      level was increased, and histological examination of lung and skin biopsies
      revealed noncaseating granulomas, indicating that her primary Sjogren's syndrome
      was complicated by sarcoidosis.

PMID- 9550601
TI  - Fas-induced apoptosis.

PMID- 9550602
TI  - Role of apoptosis on morphogenesis and therapy in malignancy.

PMID- 9550604
TI  - Hematological diseases and apoptosis.

PMID- 9550603
TI  - Rheumatoid arthritis and apoptosis.

PMID- 9550605
TI  - Apoptosis in liver disease.

PMID- 9550606
TI  - Apoptosis in neurodegenerative disorders.

PMID- 9550607
TI  - Endocrine disease and apoptosis.

PMID- 9550608
TI  - Antithrombotic treatment in ischemic cerebrovascular disease.

PMID- 9550609
TI  - Antiplatelet agents prevent cardiac events in patients with coronary artery
      disease.

PMID- 9550610
TI  - Ischemic heart disease (coronary thrombolysis).

PMID- 9550611
TI  - Cardiogenic cerebral embolism associated with atrial fibrillation.

PMID- 9550612
TI  - Anti-neutrophil cytoplasmic autoantibodies associated renal diseases and
      thrombotic microangiopathy.

PMID- 9550613
TI  - Nephrotic syndrome and anticoagulant therapy.

PMID- 9550614
TI  - Vasopressin and related disorders.

PMID- 9550615
TI  - Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes
      insipidus.
AB  - Two cases of autosomal recessive nephrogenic diabetes insipidus (NDI) were
      evaluated. Both cases were found to be compound heterozygote for missense
      mutations in the aquaporin-2 (AQP2) gene. To determine the structural-functional
      relationship, the mutated AQP2 proteins, T125M, G175R, A190T, and P262L, were
      expressed in Xenopus oocytes and examined by measurement of water permeability,
      immunoblot, and immunocytochemistry. Our results suggest that T125M and G175R are
      nonfunctional water channels, whereas the translocation to the plasma membrane is
      impaired in A190T and P262L.

PMID- 9550616
TI  - Therapeutic efficacy of vasopressin receptor antagonists.

PMID- 9550617
TI  - Diuretic therapy.

PMID- 9550618
TI  - Physiology and pathophysiology of acid-base homeostasis in the kidney.

PMID- 9550620
TI  - Unopposed stimulation of the angiotensin AT2 receptor in the kidney.

PMID- 9550619
TI  - A functional role for endogenous atrial natriuretic peptide in the maintenance of
      body fluid balance in heart failure.

PMID- 9550621
TI  - HIV-associated nephropathy: current concepts.

PMID- 9550622
TI  - Nephron reduction in man--lessons from the Os mouse.

PMID- 9550623
TI  - Progression of renal failure and lipids--is there evidence for a link in humans?

PMID- 9550624
TI  - Is persistent TGFbeta1 expression the mechanism responsible for chronic renal
      allograft loss?

PMID- 9550625
TI  - Dietary salt restriction and reduction of dialysate sodium to control
      hypertension in maintenance haemodialysis patients.

PMID- 9550626
TI  - Dialysis hypertension: dry weight and dialysis time.

PMID- 9550627
TI  - Change of paradigms in nephrology--a view back and a look forward.

PMID- 9550628
TI  - Update on reversal of left ventricular hypertrophy in essential hypertension (a
      meta-analysis of all randomized double-blind studies until December 1996).
AB  - OBJECTIVE: To provide an update on the ability of different antihypertensive
      drugs to reduce left ventricular hypertrophy in essential hypertension. DATA
      SOURCES: Relevant medical databases including MEDLINE, BIOSIS PREVIEWS, EMBASE,
      and SCISEARCH as well as review articles to December 1996. STUDY SELECTION: Meta
      analysis of all published articles including only double-blind, randomized,
      controlled clinical studies with parallel-group design. DATA EXTRACTION:
      Literature search and data extraction according to a prefixed scheme performed
      independently by two investigators. The primary parameter was reduction of left
      ventricular mass by antihypertensive therapy with placebo, diuretics, beta
      blockers, calcium channel blockers, or ACE-inhibitors. DATA SYNTHESIS: Fifty
      studies published till the end of December 1996 were identified. They comprised a
      total of 1715 patients in 13 placebo (n=165, age: 50+/-3 years) and 89 active
      treatment arms (n=1550, age: 56+/-10 years) respectively. Overall, for active
      treatment left ventricular mass index was the more reduced the greater the
      decrease in systolic blood pressure, (r=0.27; P<0.05), the longer the duration of
      therapy (r=0.36; P<0.001), and the higher the pretreatment value of left
      ventricular mass index (r= 0.53; P<0.001). Left ventricular mass index was
      decreased by 12% with ACE-inhibitors (95% CI: 9.0-14.5%), by 11% with calcium
      channel blockers (95% CI: 7.8-13.7%), by 5% with beta-blockers (95% CI: 1.2-7.3%)
      and by 8% with diuretics (95% CI: 3.9-11.1%) (overall P<0.01). Subsequent tests
      revealed that ACE-inhibitors and calcium channel blockers were more effective
      than beta-blockers in reducing left ventricular mass index (P<0.05). Similar
      differences between drug classes were found with regard to effect on left
      ventricular wall thickness (P<0.05). CONCLUSIONS: Decrease in systolic blood
      pressure, duration of antihypertensive therapy, degree of pretreatment left
      ventricular hypertrophy and antihypertensive drug class determined the reduction
      of left ventricular hypertrophy. ACE-inhibitors and calcium channel blockers were
      more potent in reducing left ventricular mass than beta-blockers, with diuretics
      in the intermediate range.

PMID- 9550629
TI  - Intoxication by star fruit (Averrhoa carambola) in six dialysis patients?
      (Preliminary report)
AB  - We observed six cases of patients in a dialysis programme who were apparently
      intoxicated by ingestion of star fruit. After ingestion of 2-3 fruits or 150-200
      ml of the fruit juice, the six patients, who had previously been stable in a
      regular dialysis programme, developed a variety of symptoms ranging from insomnia
      and hiccups to agitation, mental confusion and (in one case) death. In
      preliminary investigations to characterize the hypothetical neurotoxin in the
      fruit, an extract, when injected intraperitoneally or intracerebroventricularly
      in rats, provoked persistent convulsions of the tonic-clonic type. It appears
      that star fruit (Averrhoa carambola) contains an excitatory neurotoxin. Patients
      with renal failure on conservative or dialysis treatment should be dissuaded from
      ingestion of the fruit.

PMID- 9550630
TI  - Cell-specific regulation of alpha1(III) and alpha2(V) collagen by TGF-beta1 in
      tubulointerstitial cell models.
AB  - BACKGROUND: TGF-beta1 modulates the cellular expression of extracellular matrix
      (ECM) in several renal cell systems in vitro and is considered a determinant of
      ECM accumulation in tubulointerstitial fibrosis. METHODS: We evaluated the
      effects of TGF-beta1 on collagen transcription, expression, and removal of the
      relevant collagens by rat tubuloepithelial cells (NRK 52E) and both rat and
      monkey interstitial fibroblasts (NRK 49F, CV1) in vitro. RESULTS: TGF-beta1
      upregulated the expression of alpha1(III) collagen by fibroblasts (+300%) without
      affecting its removal. In parallel, a threefold increment of COL3A1 mRNA was
      found. Experiments of cell transfection employing CV1 fibroblasts as the unique
      suitable model, and chimaeric constructs of COL3A1 and COL5A2 promoters fused to
      the luciferase reporter gene, demonstrated a twofold stimulation of a large 1436
      COL3A1 promoter construct and negligible effects on shorter fragments, suggesting
      the presence of a positive responsive element in a region of COL3A1 promoter
      between -1375 and -579. TGF-beta1 did not influence COL5A2 mRNA and the relative
      promoter activity in renal fibroblasts. With NRK 52E cell line, TGF-beta1 induced
      comparable increment of both alpha1(III) collagen expression (+300%) and COL3A1
      mRNA (+300%) without affecting the COL3A1 promoter activity of any constructs.
      TGF-beta1 also upregulated the expression of alpha2(V) collagen chain (+500%) and
      COL5A2 mRNA (+500%) with a stimulatory effect (+100%) on a 1177 bp fragment of
      COL5A2 promoter. In this case a relevant inhibitory effect of TGF-beta1, on
      removal of alpha2(V) by supernatants of NRK 52E was also observed, indicating a
      double regulatory role of the cytokine on both transcription and removal of this
      component of ECM. CONCLUSION: Taken together these data indicate that TGF-beta1
      is a potent stimulator of alpha1(III) collagen expression by renal fibroblast
      cell lines in vitro, the basic mechanism being stimulation of COL3A1
      transcription. With renal epithelial cell lines, TGF-beta1 mainly upregulated the
      expression of type V collagen with the most relevant effect on stimulation of
      collagen transcription and inhibition of its removal. Tubular epithelial cells
      and renal fibroblasts should play distinct roles in renal fibrosis induced by TGF
      beta1 in vivo.

PMID- 9550631
TI  - Regulation of the transcription of parathyroid-hormone/parathyroid-hormone
      related peptide receptor mRNA by dexamethasone in ROS 17/2.8 osteosarcoma cells.
AB  - Previous studies have shown that dexamethasone enhanced the expression of
      parathyroid-hormone/parathyroid-hormone-related peptide (PTH/ PTHrP) receptor
      mRNA in ROS 17/2.8 osteosarcoma cells. The aim of this study was to determine
      whether the induction of PTH/PTHrP receptor expression in such osteoblast-like
      cells is regulated at the gene level. Dexamethasone increased the steady-state
      levels of PTH/PTHrP receptor mRNA twofold at 6 h, and nearly threefold at 24 h.
      The half-life of the PTH/PTHrP receptor mRNA, in the presence of actinomycin D,
      was 6 h both in untreated and in dexamethasone-treated cells. When measured by
      nuclear run-on assay, the rate of PTH/PTHrP receptor gene transcription was
      increased twofold at 24 h. PTH/PTHrP receptor mRNA expression was blocked
      completely after 24 h of treatment with cycloheximide. The binding of PTH/PTHrP
      to their receptor required the synthesis of new protein and was shown to be
      specifically dependent on the interaction of dexamethasone with the
      glucocorticoid receptor. These data indicate that the enhancing effect of
      dexamethasone on PTH/PTHrP receptor expression is rapid, requires de novo protein
      synthesis, and increases the transcription rate of the PTH/PTHrP receptor gene.

PMID- 9550632
TI  - Effects of a nitric oxide synthesis inhibitor on renal sodium handling and
      diluting capacity in humans.
AB  - BACKGROUND: Inhibition of nitric oxide (NO) synthesis has antinatriuretic and
      antidiuretic effects. Limited information is available on the role of NO in
      tubular sodium transport in the human kidney. METHODS: We studied nine healthy,
      sodium-replete males with clearance techniques during maximal diuresis. NG
      monomethyl-L-arginine (L-NMMA, 3 mg/kg priming dose plus 3 mg/kg/h) was infused
      for 3 h, to achieve steady-state inhibition of NO synthesis. Data were compared
      with a time control study. RESULTS: The effects of L-NMMA were quickly
      established and persisted through the entire infusion period. Mean arterial
      pressure increased slightly from 85+/-3 to 91+/-3 mmHg (P<0.05). Renal plasma
      flow decreased substantially, and glomerular filtration rate slightly. Large
      decreases in absolute sodium excretion, from 79+/-10 to 34+/-5 micromol/min
      (P<0.01), and fractional sodium excretion, from 0.5+/-0.0 to 0.3+/-0.0% (P<0.01),
      were associated with significant reductions in fractional lithium excretion
      (P<0.05) and maximum urine flow (P<0.01). Minimal urine sodium concentration
      decreased from 5.8+/-0.04 to 3.9+/-0.4 mmol/l (P<0.01) whereas minimal urine
      osmolality increased (P<0.05). Plasma renin activity, aldosterone and atrial
      natriuretic peptide levels did not change, whereas urinary excretions of
      guanosine 3'5'-cyclic monophosphate and of nitrite plus nitrate decreased
      slightly. CONCLUSIONS: Inhibition of endogenous NO synthesis in humans to an
      extent that raises blood pressure only mildly causes antinatriuresis, that can be
      attributed to increases in sodium reabsorption both at proximal and distal
      nephron sites. In addition, renal diluting capacity decreases. The effects in the
      diluting segment have not been reported before, and may be due to medullary
      vasoconstriction, similar to that described for angiotensin II.

PMID- 9550633
TI  - Role of nitric oxide-related mechanisms in renal function in ageing rats.
AB  - BACKGROUND: The impaired renal function and vasodilatation that accompany age
      need to be re-addressed based upon the new knowledge concerning vascular nitric
      oxide (NO)-dependent systems. The present study examined the effects of age on
      the NO-related renal response. METHODS: The study was performed in euvolaemic,
      conscious Wistar rats, aged 5 and 18 months. Renal function and haemodynamic
      measurements with fluorescent microspheres were employed to assess differences
      between groups. RESULTS: A first set of experiments showed that ageing rats had a
      reduced natriuretic and diuretic response to acetylcholine, whereas the response
      to sodium nitroprusside was preserved. In the same regard, a reduction of the
      renal functional effects of L-arginine (L-Arg) and L-glycine (L-Gly) was found in
      the older rats. In the ageing rats, these responses were accompanied by an
      enhanced effect of the L-Arg competitive analogue, NwNLA, which provoked a marked
      reduction of renal function. This effect of NwNLA was blocked by the simultaneous
      administration of a small dose of L-Arg in the ageing but not in the young rats.
      Systemic haemodynamic studies revealed that in ageing rats, NwNLA reduced renal
      blood flow and increased renal vascular resistances in a significantly higher
      proportion than in younger animals. However, flow to other organs, namely, brain,
      spleen or liver, was affected in a similar manner in both young and old rats.
      Ultrastructural alterations were found in endothelial cells, which might
      constitute the anatomical basis for the observed functional derangements.
      CONCLUSIONS: The present experiments reveal that ageing is accompanied by
      significant differences in NO-related responses in the kidney which do not appear
      to affect blood flow to other organs. The response to L-Arg and L-Arg competitive
      analogues supports the existence of a marked dependency on NO-related mechanisms
      in the ageing rats, but not of a decreased baseline activity of the NO-dependent
      pathways.

PMID- 9550634
TI  - Sequence analysis of the 'Goodpasture antigen' of mammals.
AB  - BACKGROUND: Autoimmunity to the NC1 domain of the alpha3 chain of type IV
      collagen (alpha3(IV)NC1), the Goodpasture antigen, is the cause of spontaneous
      human antiglomerular basement membrane (anti-GBM) disease, and of anti-GBM
      nephritis in several animal models. METHODS: We have derived amino acid sequences
      from alpha3(IV)NC1 for a number of mammalian species (monkey, sheep, pig, dog,
      rabbit, and rat) by RT-PCR and cDNA cloning. The GBM of some species was studied
      comparatively for binding to Goodpasture autoantibodies. RESULTS: From this work
      and other data the sequences of nine mammalian species can be aligned. Regions
      and residues that may be functionally important are identified. Alpha3(IV)NC1
      sequences were found to be less closely conserved across species than alpha1 and
      alpha2(IV)NC1, 91 to 99% in comparison to a minimum of 97% for alpha1, but these
      differences were unevenly distributed along the molecule. There was a
      particularly striking homology between rodent and human sequences in the carboxyl
      terminal region. Binding of Goodpasture autoantibodies to rat alpha3(IV)NC1 was
      poor in comparison with other species. CONCLUSIONS: Comparison of sequences and
      binding casts doubt on the importance of the carboxyl-terminal region for
      antibody binding, a region identified as a potential major epitope in previous
      studies. Sequence comparisons suggest possible reasons for the nephritogenicity
      of alpha3(IV)NC1 in active models of anti-GBM disease.

PMID- 9550635
TI  - Differences in glomerular leukocyte infiltration between IgA nephropathy and
      membranoproliferative glomerulonephritis.
AB  - BACKGROUND: An important aspect in glomerular nephritic processes is the enhanced
      influx of leukocytes into the glomerulus. METHODS: To investigate the mechanisms
      of intraglomerular leukocyte infiltration in IgA nephropathy (IgA-N) and
      membranoproliferative glomerulonephritis type I (MPGN-I), we
      immunohistochemically examined the intraglomerular expression of leukocyte
      function-associated antigen-1 (LFA-1, CD11a/CD18), macrophage-1 (Mac-1,
      CD11b/CD18) and intercellular adhesion molecule-1 (ICAM-1, CD54) together with
      glomerular deposition of C3c and fibrinogen. RESULTS: In IgA-N (n=42), LFA-1+
      cells were distributed mainly in glomeruli with intense expression of ICAM-1, and
      there was a positive correlation (P<0.001) between the number of LFA-1+ cells and
      the degree of ICAM-1 expression. Mac-1+ cells had no correlation with glomerular
      C3c deposition, but had a significant correlation with fibrinogen deposition
      (P<0.05). The number of LFA-1+ cells was significantly greater than of Mac-1+
      cells (P<0.05). The number of LFA-1+ cells was strongly correlated with that of
      CD68+ cells (P<0.00001). In MPGN-I (n= 43), on the contrary, Mac-1+ cells
      correlated only with C3c deposition (P<0.001), and they were observed mainly in
      peripheral loops of glomerular capillaries where C3c was deposited with a similar
      distribution. However, there was no relationship between LFA-1+ cells and ICAM-1
      expression. The number of Mac-1+ cells was greater than that of LFA-1+ cells
      (P<0.0001), and most Mac-1+ cells were identical to CD15+ cells. CONCLUSION:
      These results indicate the possibility that different mechanisms may cause
      glomerular leukocyte infiltration in various forms of human glomerulonephritis.
      The LFA-1/ICAM-1 pathway may play an important role in glomerular leukocyte
      infiltration in IgA-N, while the Mac-1/complement pathway may be important in
      MPGN-I. The former may promote mainly the infiltration of CD68+ cells, and the
      latter may promote that of CD15+ cells. In addition, Mac-1+ cells may act as
      fibrinogen and complement receptors in IgA-N and MPGN-I, respectively.

PMID- 9550636
TI  - Dietary and urinary risk factors for stones in idiopathic calcium stone formers
      compared with healthy subjects.
AB  - BACKGROUND: The high social-economic cost of nephrolithiasis wholly justifies the
      attempts to understand its mechanism and avoid recurrences. The influence of
      dietary habits and urinary risk factors has been evaluated, but the results were
      discrepant, probably because of differences in the methodologies used to compare
      patients and controls. METHODS: The aim was to assess dietary and urinary risk
      factors for urinary stones by comparison between 108 calcium stone formers (SF)
      and 210 healthy subjects (HS). All subjects were recruited during the same 1 year
      period. Personal characteristics, dietary habits (evaluated through a food
      frequency questionnaire) and urinary biochemical parameters were collected. The
      high predominance of men in the SF group led us to focus on the 79 SF and the 96
      HS men. RESULTS: A familial history of stones was reported more frequently in SF
      than in HS, 42.9% vs 17.6%, P<0.005. Body weight was higher in SF, 76.8+/-12.2 kg
      vs 72.8+/-9.6 kg, P=0.02; and calcium intake was lower in SF, 794.8+/-294.1 mg vs
      943.6+/-345.4 mg, P<0.01. For urinary parameters, calcium and oxalate output were
      significantly higher in SF. Urinary urea, as a reflection of daily protein
      intake, and uric acid were also higher in SF. Urinary citrate excretion related
      to body weight was lower in SF. Calciuria was significantly correlated with
      urinary urea in both SF and HS, but the correlation was stronger for SF.
      Calciuria correlated significantly with natriuria only in HS. CONCLUSIONS: The
      main differences between SF and HS were that SF had a family history of stones, a
      higher body weight, a lower daily intake of calcium, and a higher urinary output
      of calcium and oxalate. These results underline the combined role of genetic and
      nutritional factors in the pathogenesis of urinary stone formation.

PMID- 9550637
TI  - Stimulation of tubular secretion of creatinine in health and in conditions
      associated with reduced nephron mass. Evidence for a tubular functional reserve.
AB  - BACKGROUND: The increment in glomerular filtration rate (GFR) after a protein
      load has been taken to reflect the renal reserve capacity; however, this response
      is preserved in end-stage kidney disease. Tubular secretion of creatinine is
      increased in relation to the GFR in renal failure, but little is known about the
      tubular functional response to stimulation despite the fact that
      tubulointerstitial lesions are always pre-eminent in chronic renal damage.
      Therefore we decided to compare the urinary creatinine excretion (UcrV) and
      tubular secretion of creatinine (TScr) induced by a test meat meal in normal
      individuals and in individuals with reduced nephron mass. METHODS: We studied 12
      normal subjects, seven healthy uninephrectomized (kidney donors) and eight
      patients with chronic renal disease (serum creatinine ranging from 212.2 to 486
      micromol/l). They had been on a standard diet for 5 days before the studies. The
      test meal provided 80 g of animal protein. Three baseline and four stimulated
      (post-meal) 30-min simultaneous inulin and creatinine clearances were carried
      out. RESULTS: We found that normals increased more than twice the UcrV (post
      meal=329.5 +/-SEM 13.1 nmol/min/kg) and 3.4 times the TScr (114.4+/-12.7
      nmol/min/kg) after the test meal. In contrast, patients were unable to raise
      their baseline values (P<0.001), despite a normal increment in GFR. The data in
      kidney donors fell between normals and patients. Strong correlation existed
      between the stimulated (but not the baseline) TScr (P=0.003) and GFR and between
      UcrV post-meal/pre-meal ratio and GFR (P<0.0001). CONCLUSION: The increment in
      TScr resulting from a protein meal is related to the functioning nephron mass.
      Evaluation of this increment could have potential clinical relevance.

PMID- 9550638
TI  - On the prognosis of IDDM patients with large kidneys.
AB  - BACKGROUND: Approximately 10-30% of IDDM patients develop diabetic nephropathy
      depending on the metabolic control. Previous examinations on the significance of
      the kidney size prior to the manifestation of nephropathy produced varying
      results. METHODS: The present study, therefore, was designed to assess the
      correlation between sonographically determined kidney size and kidney function
      over 8 years in a follow-up examination, and to evaluate a potential risk
      pattern. Data could be collected from 73 (66%) of 110 IDDM patients with
      initially normal serum creatinine whose sonographically determined kidney volume
      (cm3 = L cm x W cm x D cm x pi/6) and kidney function (creatinine, albuminuria,
      beta2-microglobulin in serum) had been examined in 1986, and who had a diabetes
      duration of 1 month to 25 years at that time. RESULTS: 30% (11 of 37) patients
      with large kidneys (>170 cm3) reached at least one serious renal end-point
      (increase of serum creatinine by more than 50%, requirement of dialysis or kidney
      transplantation, or death in end-stage renal disease) versus one of 36 patients
      with normal kidney size (P<0.002). As many as 42% of patients with large kidneys
      developed abnormal creatinine values (>106 micromol/l) in contrast to only 20% of
      the patients with normal kidney volume (P<0.05). Six of seven patients with a
      more than 50% increase of serum creatinine from baseline showed large kidneys in
      1986, but had a normal serum creatinine, and four also a normal urine albumin
      excretion. Furthermore all five patients with more severe end-points (two deaths
      in end-stage renal disease and three patients presently requiring dialysis)
      exhibited either an increased serum creatinine or large kidneys at baseline; four
      of these, however, were still in the normoalbuminuric state in 1986. CONCLUSIONS:
      These results indicate that large kidneys might be a morphological marker for
      subsequent diabetic nephropathy, and as a consequence, renal insufficiency.

PMID- 9550639
TI  - Progression of diabetic nephropathy--is diurnal blood pressure rhythm as
      important as absolute blood pressure level?
AB  - BACKGROUND: Hypertensive non-diabetic patients who lack the normal nocturnal
      decline in blood pressure ('non-dippers') have an increased incidence of
      cardiovascular complications. Poor blood pressure control is known to exacerbate
      the decline in glomerular filtration rate in patients with diabetic nephropathy.
      METHODS: The aim of this study was to assess the contribution of abnormal blood
      pressure diurnal rhythm to the progression of diabetic nephropathy. We
      retrospectively studied 26 diabetic patients with hypertension, proteinuria and
      relentless progressive impairment of renal function due to diabetic nephropathy
      between 1990 and 1996. Patients underwent ambulatory blood pressure monitoring
      and were classified as either 'dippers' or 'non-dippers' according to their blood
      pressure diurnal rhythm. Dippers were patients whose mean sleeping blood pressure
      (both systolic and diastolic) was 10% less than blood pressure whilst awake.
      Weight, glycated haemoglobin, serum creatinine (micromol/l) and blood pressure
      (mmHg) were recorded on a 3-monthly basis. Twenty four hour urine protein
      excretion and creatinine clearance were recorded annually. The rate of decline of
      creatinine clearance was derived from serum creatinine estimation. RESULTS: In
      the 'dipper' group, the rate of decline of creatinine clearance was -2.9
      ml/min/year and in those with abnormal blood pressure diurnal rhythm it was -7.9
      ml/min/year (P<0.05). There was no significant difference in day-time mean blood
      pressures, glycated haemoglobin, age and numbers with insulin-dependent diabetes
      mellitus. CONCLUSION: We found that there was a profound effect of non-dipping
      upon the rate of decline of renal function in patients with diabetic nephropathy.

PMID- 9550640
TI  - Norepinephrine-induced blood pressure rise and renal vasoconstriction are not
      attenuated by enalapril treatment in microalbuminuric IDDM.
AB  - BACKGROUND: In non-diabetic subjects, an attenuated systemic norepinephrine (NE)
      responsiveness may contribute to the mechanisms of action of angiotensin
      converting enzyme (ACE) inhibitor treatment. We determined whether ACE inhibitor
      treatment influences systemic and renal haemodynamic responsiveness to exogenous
      NE, as well as urinary albumin excretion during NE, in microalbuminuric insulin
      dependent diabetic (IDDM) patients, representing a patient category that benefits
      by strict blood pressure control. METHODS: In seven microalbuminuric IDDM
      patients, systemic and renal responsiveness to NE, infused at individually
      determined threshold [deltamean arterial pressure (MAP)=0 mmHg], 20% pressor
      (deltaMAP=4 mmHg) and pressor (deltaMAP=20 mmHg) doses, were compared before and
      after 8 weeks treatment with enalapril, 10 mg daily. Blood glucose was clamped at
      5 mmol/l and insulin was infused at 30 mU/kg/h. RESULTS: Enalapril decreased MAP
      (P<0.05) and microalbuminuria (P<0.05), whereas effective renal plasma flow
      (ERPF) increased (P<0.01) and glomerular filtration rate remained unaltered. The
      filtration fraction tended to decline (P=0.09). The ACE inhibitor-induced fall in
      MAP disappeared at NE pressor dose, and the overall mean increase in MAP in
      response to NE was even higher with than without enalapril (P<0.05). After
      enalapril, the ERPF remained higher at all NE doses (P<0.05), but the magnitude
      of the NE-induced fall in ERPF was not altered by ACE inhibition treatment.
      Overnight urinary albumin excretion fell with ACE inhibition (P<0.05), but this
      effect was not seen during NE infusion. The angiotensin II/active renin ratio and
      serum aldosterone levels remained lower with enalapril at all NE doses (P<0.05).
      CONCLUSIONS: Enalapril does not attenuate systemic and renal vascular
      responsiveness to exogenous NE in microalbuminuric IDDM despite adequate
      inhibition of the renin-angiotensin-aldosterone system. These findings suggest
      that the effect of NE on vasoconstriction is not counteracted effectively by ACE
      inhibition treatment alone.

PMID- 9550641
TI  - Effects of low-dose nifedipine on urinary protein excretion rate in patients with
      renal disease.
AB  - BACKGROUND: The observation that proteinuria is an important determinant of the
      progression of renal disease has prompted numerous studies on the effects of
      antihypertensive agents on protein excretion. Reports on the proteinuric effects
      of calcium-channel blockers are quite controversial. It has been suggested that
      the short-acting dihydropyridine calcium-channel blocker nifedipine increases
      protein excretion by interference with tubular protein reabsorption. METHODS: In
      a randomized controlled trial 10 patients with renal disease and proteinuria were
      treated with a dose of 10 mg nifedipine o.d. (slow release formulation) for 1
      week. The acute effects on renal and systemic haemodynamics and on urinary
      albumin, IgG, and beta2-microglobulin excretion were investigated during a
      clearance study in the supine position after the first dose. After 1 week of
      treatment urinary protein excretion rates were measured in 24-h urine samples
      collected in the ambulatory patient in consecutive fractions of 4-8 h during
      normal daily activities. RESULTS: After the first dose nifedipine lowered mean
      arterial blood pressure in the supine position by 7+/-1 mmHg (<0.01), attenuated
      proximal tubular sodium reabsorption (fractional excretion of sodium 3.48+/-0.49
      vs 2.62+/-0.35% during control, P<0.02), but did not affect proximal tubular
      protein reabsorption (fractional urinary excretion of beta2-microglobulin 0.97+/
      0.30 vs 0.98+/-0.32% during control, NS). The decrease in blood pressure was not
      accompanied by decreases in urinary albumin or IgG excretion rates. The
      selectivity index as well as GFR, RPF, and FF did not change. Continued treatment
      for 1 week with nifedipine did not influence 24-h protein excretion. However, we
      observed a rise of proteinuria during daily activities in the first 4 h after
      drug intake compared to the start of the study with the patients in supine
      position. During control measurements there was a slight increase in proteinuria.
      During nifedipine the increase in proteinuria was more marked and correlated with
      the selectivity index. CONCLUSIONS: (1) Nifedipine 10 mg orally did not impair
      tubular protein reabsorption. (2) Nifedipine had no immediate antiproteinuric
      effect despite the observed blood pressure reduction. (3) Nifedipine increased
      proteinuria in ambulatory urine collections. This latter observation might
      explain the seemingly different effects of dihydropyridine calcium-channel
      blockers as reported in previous studies.

PMID- 9550642
TI  - The effect of metabolic control on rate of decline in renal function in insulin
      dependent diabetes mellitus with overt diabetic nephropathy.
AB  - BACKGROUND: Strict glycaemic control has been shown to reduce the risk of
      developing diabetic nephropathy. In established nephropathy, however, the impact
      of glycaemic control on prognosis is less clear. Therefore we investigated the
      effect of long-term glycaemic control on the decline in renal function in insulin
      dependent diabetic patients with overt nephropathy. METHODS: The study was
      performed at two hospital-based diabetes centres in western Sweden. The study was
      an observational retrospective follow-up study in 158 insulin-dependent diabetics
      with proteinuria with a mean (+/-SD) age of 36+/-9 years and a diabetes duration
      of 22+/-8 years. The change in glomerular filtration rate was measured as 51Cr
      EDTA clearance for a median of 8 years (range 1-17). Glycaemic control was
      determined with measurements of glycated haemoglobin A1c. RESULTS: The decline in
      glomerular filtration rate was 3.8+/-3.7 ml/min/year. The blood pressure was
      143/82+/-15/7 mmHg and the mean glycated haemoglobin was 8.7+/-1.6%. The
      correlation coefficient between glycated haemoglobin and decline in glomerular
      filtration rate was -0.39 (P<0.0001 ) and between decline in glomerular
      filtration rate and systolic and diastolic blood pressure -0.17 (P=0.03) and 
      0.29 (P=0.003) respectively. In patients with glycated haemoglobin <8.0% and
      diastolic blood pressure <85 mmHg the decline in glomerular filtration rate was
      1.7+/-2.3 ml/min/year. CONCLUSIONS: In this retrospective observational study,
      effective blood-pressure control was associated with a low rate of decline in
      renal function and a low urinary albumin excretion. The correlation between
      glycaemic control and decline in renal function indicates that poor glycaemic
      control can accelerate the loss of renal function in diabetic nephropathy.

PMID- 9550643
TI  - Evidence for disturbed S-adenosylmethionine : S-adenosylhomocysteine ratio in
      patients with end-stage renal failure: a cause for disturbed methylation
      reactions?
AB  - BACKGROUND: Elevated homocysteine concentrations have been associated with
      premature arteriosclerosis and with impairment of key methylation reactions
      through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In
      end-stage renal failure high homocysteine concentrations are commonly found but
      thus far the concentrations of related adenosylated metabolites in plasma have
      not been assessed. METHODS: In this prospective study we determined plasma
      homocysteine and related metabolites in 25 patients on regular haemodialysis, and
      in 40 healthy volunteers. Blood samples from patients were drawn immediately
      before and in 10 patients additionally after the dialysis session. RESULTS: Folic
      acid and vitamin B12 in plasma were similar in patients (mean +/- SEM 25+/-2
      nmol/l and 400+/-41 pmol/l respectively) and controls (24+/-3 and 324+/-23
      respectively). In patients plasma homocysteine, S-adenosylmethionine and S
      adenosylhomocysteine were markedly elevated (36.6+/-3.6 micromol/l, 381+/
      32nmol/l and 1074+/-55 nmol/l respectively) compared to the control values (6.8+/
      0.4 micromol/l, 60+/-3 nmol/l and 24.4+/-1.1 nmol/l respectively) whereas the
      molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was
      significantly decreased (0.36+/-0.02 and 2.7+/-0.2 in patients and controls
      respectively). Haemodialysis failed to normalize the abnormal levels of these
      metabolites. CONCLUSION: Since the ratio of S-adenosylmethionine : S
      adenosylhomocysteine is closely linked to the activity of numerous enzymatic
      methylation reactions, these results suggest that methylation may be impaired in
      these patients.

PMID- 9550644
TI  - Bone alkaline phosphatase in children with chronic renal failure.
AB  - BACKGROUND: With the introduction of a new immunoradiometric assay based on two
      monoclonal antibodies (Tandem-Ostase, Hybritech) the determination of bone
      alkaline phosphatase (BAP) to evaluate bone metabolism in chronic renal failure
      has become easier and more valid. SUBJECTS AND METHODS: Using this test we
      investigated BAP in a total of 90 paediatric patients, 42 (9.2+/-5.5 years) with
      chronic renal failure on conservative treatment, 22 (9.5+/-5.4 years) under
      chronic dialysis, and 26 (16.2+/-5.9 years) after renal transplantation, compared
      to 203 controls (10.1+/-5.7 years). RESULTS: The physiological age dependency
      found in controls including two peaks during infancy and puberty was distinctly
      disturbed in chronic renal failure. However, in patients BAP significantly
      correlated with height velocity rather reflecting the last 6 (r=0.56 P<0.001)
      than the last 12 months. Although BAP correlated well with total alkaline
      phosphatase (TAP; r=0.95 P<0.001), a significant correlation with the serum level
      of the intact parathyroid hormone could only be detected for BAP (r=0.45 P<0.001)
      but not for TAP (r=0.19 n.s.). Furthermore, BAP positively correlated with
      trabecular (n=40; r=0.40 P<0.05) and inversely with cortical bone density (n=19;
      r=-0.58 P<0.01) but no relationship was found with conventional X-ray.
      CONCLUSION: BAP determined by the new radioimmunoassay seems to represent an
      additional diagnostic tool to assess growth and bone turnover in paediatric
      patients with chronic renal failure that is complementary to the information
      provided by X-ray and total alkaline phosphatase.

PMID- 9550645
TI  - Signal-averaged ECG abnormalities in haemodialysis patients. Role of dialysis.
AB  - BACKGROUND: Late potentials (LP) on the signal-averaged electrocardiogram (SAECG)
      are predictive of malignant ventricular arrhythmias and sudden cardiac death in
      patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction,
      both regional and global, as well as supraventricular and ventricular arrhythmias
      are reported in a high percentage of patients with end-stage renal failure
      (ESRF). The aim of the study was to assess the prevalence of LP and the effects
      of haemodialysis on the SAECG of ESRF patients. METHODS: SAECG was recorded
      immediately before and within 30 min after the end of dialysis in 48 patients in
      sinus rhythm, free of conduction disturbances on ECG and of signs of congestive
      heart failure. Serum electrolytes were sampled together with the SAECG
      recordings. An echo-Doppler exam was performed within 2 weeks of the study.
      SAECGs were adequate for analysis in 45/48 patients. LP were present when at
      least two of the following criteria were fulfilled: QRS duration < or = 115 ms,
      LAS40 < or = 38 ms, RMS40 > or = 38 microV at 40 Hz high pass bidirectional
      filter, and noise <0.7 microV. RESULTS: LP were detected in 12/45 patients (25%)
      on the SAECG before dialysis; of these 12 patients, seven had a history of a
      previous myocardial infarction and two had documented coronary artery disease
      (CAD). A significant greater wall motion score index--calculated on a 16 segment
      model--was reported in patients with LP (1.20+/-0.20 vs 1.01+/-0.03, P<0.01),
      while left ventricular mass was comparable in the two groups of patients. At the
      end of dialysis, a significant prolongation of fQRS duration was found both at 25
      and 40 Hz filters (from 98+/-11 to 106+/-16 ms and from 97+/-12 s to 102+/-13 ms,
      respectively, P<0.001). A significant inverse relationship was seen between the
      percentage of dialysis-induced serum potassium reduction and fQRS changes at 40
      Hz (r=-0.68, P<0.001). CONCLUSIONS: LP were detected in a significant proportion
      of dialysis patients, probably related to underlying CAD with left ventricular
      dysfunction. Prolongation of fQRS after dialysis could be explained by the acute
      reduction in serum potassium levels.

PMID- 9550646
TI  - Evidence for an independent role of metabolic acidosis on nutritional status in
      haemodialysis patients.
AB  - BACKGROUND: Malnutrition in haemodialysis (HD) patients has been referred to
      underdialysis with low protein intake, and to acidosis. However, the separate
      effects of underdialysis and acidosis on nutrition have not been clearly
      demonstrated. To evaluate the role of the dialysis dose and of metabolic acidosis
      on nutrition, we measured the predialysis serum HCO3, pH, serum albumin, PCRn,
      Kt/V, and BMI in 81 uraemic patients on maintenance bicarbonate HD for 93+/-80
      months. Patients with chronic liver diseases, malignancies, and cachexia were
      excluded. RESULTS: Mean age was 59+/-17 years, Kt/V was 1.29+/-0.21, PCRn 1.06+/
      0.22 g/kg/day, serum albumin 4.07+/-0.28 g/dl, BMI 23+/-4 kg/m2, HCO3 21.1+/-1.9
      mmol/l, pH 7.36+/-0.04. Serum albumin showed a significant direct correlation
      with: PCRn (P=0.001), HCO3 (P=0.001), pH (P=0.002), but no correlation with Kt/V
      and BMI. Serum HCO3 correlated inversely with PCRn (P=0.027). Multiple regression
      analysis confirmed the significant role of serum bicarbonate and age, but not of
      Kt/V, on serum albumin concentrations. The role of PCRn appeared to be marginal
      compared to serum bicarbonate in determining serum albumin levels. Dividing
      patients into two groups, serum albumin was 3.96+/-0.22 g/dl with HCO3 < or = 20
      mmol/l and 4.18+/-0.31 g/dl in those with serum HCO3 > or = 23 mmol/l (P=0.002).
      PCRn in the same groups was respectively 1.14+/-0.24 g/kg/day and 1.01+/-0.23
      g/kg/day (P=0.03). Most importantly, serum albumin levels did not appear to be
      affected by the dialysis dose, with Kt/V ranging from 0.90 to 1.88. CONCLUSIONS:
      In HD patients with adequate Kt/V, metabolic acidosis exerts a detrimental effect
      on serum albumin concentrations partially independently of the protein intake, as
      evaluated by PCRn. In the presence of moderate to severe metabolic acidosis, PCRn
      does not reflect the real dietary protein intake of the patients, probably as a
      result of increased catabolism of endogenous proteins. For this reason PCRn
      should be considered with caution as an estimate of the dietary protein intake in
      HD patients in the presence of metabolic acidosis.

PMID- 9550647
TI  - Factor VII coagulant activity (VIIc) and hypercoagulability in chronic renal
      disease and dialysis: relationship with dyslipidaemia, inflammation, and factor
      VII genotype.
AB  - BACKGROUND: Factor VII coagulant activity (VIIc) is implicated in cardiovascular
      disease (CVD) risk in the general population. VIIc is correlated with
      hyperlipidaemia and influenced by a polymorphism of the factor VII gene and could
      contribute to thrombotic risk in patients with renal disease. METHODS: We studied
      VIIc in 100 patients with chronic renal disease or on maintenance dialysis and
      examined its relationship with dyslipidaemia, a marker of coagulation activation
      prothrombin fragment F1+2 (F1+2), the acute-phase reactant and coagulation factor
      fibrinogen, a mediator of the inflammatory response interleukin-6 (IL6), and the
      factor VII R353Q polymorphism. RESULTS: VIIc (186+/-58 vs 140+/-37, % standard,
      P<0.0001) and F1+2 (0.51 vs 0.30 nM, median, P<0.0001) were increased in the
      patients with renal disease compared with the control group, consistent with a
      hypercoagulable state. Patients and controls heterozygous for the factor VII
      R353Q polymorphism, had 35% lower VIIc than homozygotes for the R353 allele,
      indicating that the Q353 allele could confer genetic protection from thrombotic
      risk. There was a significant correlation between VIIc and F1+2 (r=0.26, P<0.05),
      total and VLDL cholesterol, and triglycerides, but the correlation with lipids
      did not differ by genotype. VIIc and F1+2 also correlated with increased
      concentration of IL6 and fibrinogen, and inversely with albumin, suggesting that
      a persistent inflammatory response could contribute to a hypercoagulable state,
      possibly via cytokine induced activation of the endothelium, or by induction of
      monocytes to express tissue factor. Patients with CVD complications or a history
      of myocardial infarction did not have higher VIIc or F1+2 than those without CVD.
      CONCLUSIONS: VIIc was significantly increased in renal disease states and
      strongly influenced by a common polymorphism of the factor VII gene, but the
      increase in VIIc and its correlation with lipids was not genotype specific. VIIc
      correlated with evidence of increased coagulation activation and persistence of
      an inflammatory response. A persistent inflammatory response and the
      dyslipidaemia of renal disease may contribute to coagulation activation and
      increased cardiovascular risk. Prospective studies are required to evaluate
      increased VIIc as a thrombotic risk factor in chronic renal disease.

PMID- 9550648
TI  - The effects of exercise training on muscle atrophy in haemodialysis patients.
AB  - BACKGROUND: Patients with end-stage renal disease on haemodialysis (HD) have
      limited work capacity. Many structural and functional alterations in skeletal
      muscles contribute to this disability. METHODS: To evaluate the effects of
      exercise training on uraemic myopathy, seven HD patients (mean age 44.1+/-17.2
      years) were studied. Open muscle biopsies were taken from their vastus lateralis
      muscle before and after a 6-month exercise rehabilitation programme and examined
      by routine light- and transmission electron-microscopy. Histochemical stainings
      of frozen sections were performed and morphometric analysis was also applied to
      estimate the proportion of each fibre type and the muscle fibre area.
      Spiroergometric and neurophysiological testing and peak extension forces of the
      lower limbs were measured before and after exercise training. RESULTS: All
      patients showed impaired exercise capacity, which was associated with marked
      muscular atrophy (mean area 2548+/-463 microm2) and reduction in muscle strength
      and nerve conduction velocity. All types of fibres were atrophied, but type II
      were more affected. The ultrastructural study showed severe degenerative changes
      in skeletal muscle fibres, mitochondria, and capillaries. Exercise training had
      an impressive effect on muscular atrophy; in particular the proportion of type II
      fibres increased by 51% and mean muscle fibre area by 29%. Favourable changes
      were also seen on the structure and number of capillaries and mitochondria. These
      results were confirmed by a 48% increase in VO2 peak and a 29% in exercise time,
      as well as an improvement in the peak muscle strength of the lower limbs and in
      nerve conduction velocity. CONCLUSIONS: Skeletal muscle atrophy in HD patients
      contribute to their poor exercise tolerance. The application of an exercise
      training rehabilitation programme improved muscle atrophy markedly, and therefore
      had beneficial effects in overall work performance.

PMID- 9550649
TI  - Simultaneous peritoneal dialysis catheter insertion and removal in catheter
      related infections without interruption of peritoneal dialysis.
AB  - Catheter-related infections result in high patient morbidity, the need for
      temporary haemodialysis, and high costs. These infections are the main cause of
      limited technique survival in peritoneal dialysis. We introduced a protocol for
      the simultaneous peritoneoscopic insertion and removal of peritoneal catheters in
      patients with catheter-related infections. Peritoneal dialysis was continued the
      day after surgery using low-volume dwells and a dry abdomen during the daytime.
      The dialysate leukocyte count had to be below 100/mm3 before exchanging
      catheters, which was performed under antibiotic therapy based on culture
      sensitivity. The old catheter was removed after the new catheter had been
      inserted in the opposite abdominal region. CAPD patients were switched to APD for
      1 week, which made prolonged hospitalization necessary. Simultaneous catheter
      insertion and removal was performed 25 times in 22 patients on CCPD and 15 times
      in 14 patients on CAPD. In CCPD patients, peritoneal dialysis was restarted after
      1.0+/-0.1 days in 24 cases. One patient had sufficient residual renal function
      and discontinued CCPD until day 10. In 10 CAPD patients (11 procedures) APD was
      started 1.3+/-0.2 days after the procedure with CAPD beginning 7.1+/-0.6 days
      thereafter. Three CAPD patients preferred haemodialysis and restarted CAPD 10.0+/
      2.1 days after surgery. One patient continued CAPD the day after surgery. In
      addition to minor complications (e.g. position-dependent outflow problems),
      dialysate leakage occurred in two patients. Two patients developed peritonitis
      within the first 30 days after surgery, one of which was procedure related. One
      patient had severe lower gastrointestinal bleeding 2 weeks after the procedure,
      which was not related to the catheter replacement. Ultimately, in 38 of 40
      procedures the patients could successfully continue peritoneal dialysis. We
      conclude that simultaneous insertion and removal of a peritoneal dialysis
      catheter without interruption of peritoneal dialysis is a safe procedure in
      patients with catheter-related infections.

PMID- 9550650
TI  - Race and delayed kidney allograft function.
AB  - BACKGROUND: Allograft survival among black recipients is poorer than among
      whites. Delayed allograft function is associated with a significant reduction in
      renal allograft survival. The relationship between delayed allograft function and
      black race is incompletely specified and was the focus of this investigation.
      METHODS: A non-concurrent study of 325 recipients of cadaveric allografts
      followed for the occurrence of delayed allograft function defined as dialysis
      during the first week following transplantation for the principal analysis. A
      secondary definition of delayed allograft function was formulated based on the
      serum creatinine 2 weeks after transplantation. Unadjusted and adjusted logistic
      regression analysis were used to examine the unconfounded relationship between
      race and delayed allograft function. RESULTS: Fifty-seven of 91 (62.6%) black
      recipients experienced delayed allograft function compared to 113 of 234 (48.3%)
      whites. The odds ratio for black race as a predictor of delayed allograft
      function was 1.80, P=0.02, (95% CI, 1.09, 2.95). This finding was stable despite
      adjustment for other predictors of delayed allograft function in a multivariate
      model, but the precision of this estimate was less (P=0.10) because of missing
      data. Additionally, adjusted models with imputed values for missing covariates,
      models using a secondary definition of delayed allograft function, and models
      excluding patients whose cyclosporin therapy was delayed, all consistently
      demonstrated a similar association between black race and delayed allograft
      function. CONCLUSIONS: This study demonstrated an increased risk of delayed
      allograft function among black recipients. This relationship may play a role in
      the poorer allograft outcomes experienced by black recipients. Given the negative
      effect of delayed allograft function on allograft survival, efforts to identify
      its modifiable risk factors should be a high priority.

PMID- 9550651
TI  - Advantage of antithymocyte globulin induction in sensitized kidney recipients: a
      randomized prospective study comparing induction with and without antithymocyte
      globulin.
AB  - BACKGROUND: Sensitized kidney allograft recipients require special management to
      improve their outcome. One strategy is heavy immunosuppression with
      antilymphocyte antibodies. Controversy continues about the actual advantage of
      induction protocols whilst infections and cancers are a constant risk. In
      addition, little is known about how to handle sensitized patients with low levels
      of sensitization. METHODS: In this study, we randomized sensitized renal
      transplant recipients, who received prophylactic treatment with or without
      antithymocyte globulin (ATG), in addition to a standard triple regimen consisting
      of cyclosporin, steroids and azathioprine at ATG discontinuation. The induction
      treatment consisted of a low-dose ATG course over 10 days. Randomization was
      stratified on the maximum PRA, according to the five following classes: 5% < PRA
      < or = 20%, 20% < PRA < or = 40%, 40% < PRA < or = 60%, 60% < PRA < or = 80% and
      80% < PRA < or = 100%. RESULTS: Eighty nine patients were enrolled: 47 patients
      received ATG and 42 did not. ATG induction lowered the incidence of biopsy-proven
      acute rejection episodes from 64 to 38%, increased 1 year graft survival from 76
      to 89% and was associated with a higher 1 year inulin clearance (37+/-15 vs 49+/
      18 ml/min). ATG-associated side effects were restricted to leucopenia and
      thrombocytopenia, whereas bacterial and viral infections, gammopathies and
      cancers did not occur more frequently. ATG induction benefited all sensitized
      patients, and not only the hypersensitized patients. CONCLUSIONS: We conclude
      that ATG induction is beneficial for all sensitized patients, regardless of their
      level of sensitization, with regard to acute rejection episodes, graft survival
      and graft function. Low-dose ATG is sufficient and prevents additional
      complications.

PMID- 9550653
TI  - Combined heart-kidney transplantation: report on six cases.
AB  - BACKGROUND: Combined heart-kidney transplantation has become a new therapeutic
      solution for patients with coexisting, irreversible heart and kidney failure.
      Though this combined approach has several theoretical advantages over sequential
      transplantation, it has yet to be established that it does not jeopardize patient
      and graft outcomes. We here report our experience with six cases of combined
      heart-kidney transplantation from single donors and review the literature in
      order to clarify this issue. METHODS: Four patients were kidney-transplant
      candidates with severe heart failure and two were heart-transplant candidates
      with independent chronic renal failure. Donors were selected on the basis of
      weight and size matching, ABO compatibility, and negative T-cell cross-match.
      RESULTS: The heart was always grafted first. The surgical procedure was
      uneventful in all cases. Heart and kidney function recovered quickly in all
      patients. Two patients died, one at day 45 from heart subacute rejection and the
      other one at day 157 from cerebral haemorrhage. The four remaining patients are
      alive 23-84 months after transplantation (2-year survival rate: 67%) and have
      well-functioning kidneys (creatinine clearance 31-83 ml/min) and hearts (left
      ventricular ejection fraction 53-83%). Remarkably, four of six patients had no
      acute rejection episode of either organ. These patient and graft outcomes are in
      agreement with previous reports and compare favourably with the results of
      isolated heart and kidney transplantation. CONCLUSIONS: Combined heart-kidney
      transplantation from the same donor should be proposed to patients who would
      qualify for transplantation of each organ within a few years.

PMID- 9550652
TI  - Expression of inducible lymphocyte costimulatory molecules in human renal
      allograft.
AB  - BACKGROUND: CTLA-4/CD28-B7 and CD40-CD40L interactions constitute two key
      costimulatory pathways in lymphocyte signalling during experimental allograft
      rejection. Studies on the expression of these molecules in human transplant
      rejection are still lacking. METHODS: The immunohistochemical study was performed
      on renal biopsies obtained for various clinical complications from 25 renal
      transplant patients. Expression of B7-1 and B7-2 and their counter-receptor CTLA
      4, and of CD40 and its counter-receptor CD40L was examined. RESULTS: In acute
      rejection a focal intense infiltration of B7-1+ and B7-2+ cells (mainly CD20-
      CD14+) and of CTLA-4+ T lymphocytes (mainly CD8+) was present. In contrast, CD40
      and CD40L were rarely expressed. Accumulations of T lymphocytes were found in the
      interstitium in the same area containing B7-1+ and B7-2+ cells. The scattered
      CD40L+ cells found in the T-cell infiltrate exhibited the CD4+ phenotype. In
      chronic rejection only a few B7-1+, B7-2+ or CTLA-4+ cells were detectable. In
      contrast, several CD40L+CD4+ cells were present both in the interstitium and in
      glomeruli. Moreover, an intense expression of CD40 on the endothelium was
      observed. In patients with cyclosporin nephrotoxicity cells positive for B7-1, B7
      2, CTLA-4, CD40, or CD40L were absent. CONCLUSIONS: These results demonstrate a
      differential expression of costimulatory molecules in renal biopsies of allograft
      recipients undergoing acute or chronic rejection. Moreover, their detection may
      prove useful to discriminate rejection from cyclosporin nephrotoxicity.

PMID- 9550654
TI  - Is blood pressure related to kidney size and shape?
AB  - OBJECTIVE: To examine the relationship between blood pressure and the size and
      shape of the kidneys in healthy volunteers from the community. DESIGN: A cross
      sectional community-based study of normal volunteers in Portsmouth City,
      Hampshire, UK. SUBJECTS: Subjects numbered 185 (99 female), aged 19-66 years.
      RESULTS: Blood pressure was higher in men, and in those with higher body mass
      index. Both systolic and diastolic blood pressure were correlated with the
      derived kidney volume. However, when corrected for age, sex and BMI the
      relationship was not statistically significant. Blood pressure correlated
      inversely with the width : length ratio of the left kidney. CONCLUSIONS: Blood
      pressure was not correlated with kidney size in this group of adults.

PMID- 9550655
TI  - Hepatitis C virus genotypes in patients on renal replacement therapy.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is prevalent among patients
      on renal replacement therapy. Viral genomic differences can contribute to
      diversities in clinical manifestation. The distribution of HCV genotypes depends
      on the geographical region and risk factors unique to the patient population. We
      determined the HCV genotypes in patients on renal replacement therapy in order to
      define the genotypic profile and examine the relationship between genotype, mode
      of renal replacement therapy, and the prevalence as well as severity of liver
      disease. METHODS: HCV genotypes were determined by restriction fragment length
      polymorphism and sequencing of the 5'-untranslated region in 21 renal allograft
      recipients, 29 patients on dialysis, and 26 non-renal failure controls. RESULTS:
      The most prevalent genotype among patients with renal failure was 1b (78%),
      followed by 1a (10%) and 6a (8%). 2 renal allograft recipients with 6a infection
      probably acquired HCV from the same donor. The relative prevalence of HCV
      genotypes was similar to that of controls. While renal allograft recipients
      demonstrated more severe liver disease than dialysis patients, the prevalence and
      severity of chronic hepatitis were similar between patients with 1b and non-1b
      infection. CONCLUSIONS: Resemblance of genotype distribution in Hong Kong to that
      of southern China and east Asia suggests common epidemiological evolution of HCV
      infection in these regions. Our results imply that in addition to viral
      characteristics, host factors such as the immunosuppressed state play an
      important role in the pathogenesis of liver disease in these patients.

PMID- 9550656
TI  - Angiotensin-converting-enzyme insertion/deletion genotype and long-term renal
      allograft survival.
AB  - BACKGROUND: Increased activity of the renin-angiotensin system has been
      implicated in decreased long-term survival of renal allografts. Recent studies
      suggest that a deletion variant of the angiotensin-converting enzyme, associated
      with increased humoral and tissue activity of this enzyme, may be a risk factor
      for the development of diabetic nephropathy and the progression of IgA
      nephropathy. The present study was conducted to determine whether the deletion
      variant of the angiotensin-converting-enzyme gene influences the long-term
      outcome in renal-transplant recipients. METHODS: We examined the relationship
      between recipient angiotensin-converting-enzyme genotype and clinical outcome in
      patients with a surviving allograft of at least 10 years (median survival 156
      months, n= 86). Patients with an allograft survival of less than 3 years served
      as controls (median survival 10.4 months, n=87). RESULTS: Genotype distribution
      in long-term renal allograft survivors (II, 18; ID, 41; DD, 27; qD, 0.55) was
      similar to that in the control group (II, 12; ID, 53; DD, 22; qD, 0.56), and
      there were no significant differences between the genotypic groups in either
      cases or controls. Long-term survivors were more often female (58 vs 38%) and
      less often hypertensive (67 vs 77%). Both recipient and donor age were markedly
      lower in the long-term survivor group, whereas number of HLA mismatches and cold
      ischaemia time were comparable between cases and controls. CONCLUSIONS: This
      study does not support the hypothesis that the angiotensin-converting-enzyme
      insertion/deletion polymorphism is an important determinant of long-term
      transplant survival in Caucasian patients undergoing renal transplantation.

PMID- 9550657
TI  - Stability of access resistance during haemodialysis.
AB  - BACKGROUND: Access blood flow (Qac) is considered a useful indicator in the
      surveillance of haemodialysis access function. However, changes in Qac may be due
      to changes in blood pressure and/or to changes in access resistance (AR).
      METHODS: Weekly readings of Qac, cardiac output, and arterial blood pressure
      measured early and late during haemodialysis were obtained in 11 patients for a
      period of 3 weeks. Qac was determined from thermodilution of extracorporeal blood
      returning to the patient with reversed placement of blood lines and by
      measurement of arterial and venous blood temperatures in the extracorporeal
      circulation. Data are given as mean +/- SE. RESULTS: Qac dropped as mean arterial
      pressure (MAP) and total peripheral resistance (TPR) decreased, but increased
      when MAP and TPR increased. Linear regressions between the change in access flow
      and the change in MAP (deltaQac%=0.80*deltaMAP%-1.6, r2=0.39), and the change in
      TPR (deltaQac%= 0.54*deltaTPR%-9.2, r2=0.35) respectively, were significant
      (P<0.001). Whereas Qac significantly decreased (-8.4+/-3.3%, P<0.01) during the
      same treatment, AR remained unchanged (4.7+/-3.2%; P=NS). AR for all studies was
      16.5+/-1.0 peripheral resistance units (1 PRU=2.226 kPa min l(-1)). There was a
      trend for resistance to increase (5.1+/-2.6%, P=NS) and for flow to decrease (
      6.1+/-2.3%, P=NS) during the 3 weeks of the study. CONCLUSION: Qac measured
      during haemodialysis is variable and depends on haemodynamics, but AR is
      constant. AR is related to the physical structure of the peripheral access.
      Because of its intradialytic stability AR may be better suited as an indicator of
      access function.

PMID- 9550658
TI  - Adequacy of haemodialysis with cuffed central-vein catheters.
AB  - Cuffed central-venous haemodialysis catheters are emerging as an alternative
      permanent haemodialysis vascular access. There is limited data regarding the
      adequacy of dialysis with prolonged used of these catheters. We conducted a
      prospective study comparing three commonly used cuffed central-venous
      haemodialysis catheters: (1) PermCath, Quinton Instrument Co, Seattle; (2) Tesio,
      Med Comp, Inc, Harleysville PA; (3) VasCath Soft Cell, Bard Instrument Company,
      Toronto, and compared them with control patients dialysing with arteriovenous
      access (AV) access. We randomly assigned 64 patients who needed prolonged
      temporary vascular access to placement of one of three catheters. The control
      group comprised 222 patients dialysing simultaneously in the same units with AV
      access. METHODS: All patients were dialysed with identical machines and kidneys.
      Maximal effort were made with every catheter to optimize achievable blood flow.
      Catheters with mechanical problems were treated first with urokinase and then
      fibrin sheath catheter stripping. The mean blood flow was determined by averaging
      mean blood flows from 30 consecutive treatments. Reliability of catheter was
      defined as percentage of treatments that were performed at a median blood flow of
      350 ml/min or above during these 30 treatments. Kt/V was measured monthly and
      calculated using the single-pool Daugirdas formula. Haemodialysis prescription
      were adjusted for Kt/V above 1.2. Recirculation was measured using two-needle low
      blood-flow technique. RESULTS: The mean blood flows were (PermCath 383.6 ml/min,
      Tesio 396.3 ml/min, VasCath 320.4 ml/min). PermCath and Tesio had comparable mean
      blood flows and were significantly higher than VasCath (P<0.005). Reliability of
      catheters were (PermCath 86.9%, Tesio 81.6%, VasCath 42.3%). Tesio and PermCath
      were equally reliable and both were more reliable than VasCath (P<0.005). Had the
      target for reliability been 300 ml/min all three catheters would have been
      equally reliable. Negative arterial pressure in excess of 300 mmHg prevented
      faster blood flows in 98% of instances. None of the catheters performed as well
      as the control population with AV access (mean blood flow 437ml/min, reliability
      96%, P<0.005). Recirculation rates were 3.7% for PermCath 3.9% for Tesio, and 4%
      for VasCath. All patients weighing less than 85 kg acheived a Kt/V of 1.2 with a
      4-h treatment. For comparison purposes when Kt/V was normalized to a 70-kg
      patient the results were PermCath 1.42. Tesio 1.44, VasCath 1.19, AV access 1.64.
      SUMMARY: All three catheters are capable of providing adequate haemodialysis
      although large patients will need extended treatment times. The PermCath and
      Tesio provide blood flow and reliability superior to the VasCath. Blood flow is
      limited in all catheters by inflow, as evidenced by negative arterial pressure.
      All catheters had acceptable recirculation. AV access is superior in terms of
      blood flow and reliability to all tested catheters.

PMID- 9550660
TI  - Irreversible tubulointerstitial nephropathy associated with prolonged, massive
      intake of vitamin C.

PMID- 9550659
TI  - Indinavir crystal deposits associated with tubulointerstitial nephropathy.

PMID- 9550661
TI  - Propylthiouracil-induced acute interstitial nephritis with acute renal failure
      requiring haemodialysis: successful therapy with steroids.

PMID- 9550662
TI  - A case of Becker muscular dystrophy and massive myoglobinuria with minimal renal
      manifestations.

PMID- 9550663
TI  - Seizures complicating adult Henoch-Schonlein purpura.

PMID- 9550664
TI  - Evaluation of a patient with hypertension and mild renal failure in whom facial
      and digital abnormalities are noted.

PMID- 9550665
TI  - Nephrotic syndrome after successful renal angioplasty.

PMID- 9550666
TI  - Despite low plasma renin ACE inhibitor treatment causes recovery from acute renal
      failure in a patient with malignant hypertension.

PMID- 9550667
TI  - Steroids for deep-infection-associated glomerulonephritis: a two-edged sword.

PMID- 9550668
TI  - Secondary hyperparathyroidism resistant to active vitamin D is not unique to
      renal failure--observation in a patient with distal tubular acidosis and
      pancreatogenic malabsorption.

PMID- 9550669
TI  - Parvovirus B19 infection and unresponsiveness to erythropoietin therapy in
      haemodialysis patients.

PMID- 9550670
TI  - A patient on haemodialysis with necrotizing fasciitis of the left arm.

PMID- 9550671
TI  - Reflex sympathetic dystrophy following vascular access surgery for haemodialysis:
      influence of peripheral ischaemia?

PMID- 9550672
TI  - The dialysis patient with headache and sudden hypotension: consider pituitary
      apoplexy.

PMID- 9550673
TI  - Kaposi's sarcoma and cold abscess of the graft in a renal transplant recipient.

PMID- 9550674
TI  - Ureteric aspergilloma as the cause of ureteric obstruction in a renal transplant
      recipient.

PMID- 9550675
TI  - Ureteric obstruction: an unusual complication of total hip replacement.

PMID- 9550676
TI  - Subcutaneous nodules and pneumonia in a kidney transplant recipient.

PMID- 9550677
TI  - Images in nephrology. Vascular catheter apparently well-placed.

PMID- 9550679
TI  - Contrast-associated nephropathy--old clinical problem and new therapeutic
      perspectives.

PMID- 9550678
TI  - Brains and bones.

PMID- 9550680
TI  - The clinical spectrum of shunt nephritis.

PMID- 9550681
TI  - The BSM-1 vitamin D receptor polymorphism and secondary hyperparathyroidism.

PMID- 9550682
TI  - Perirenal haematoma as the presenting feature of polyarteritis nodosa: one more
      case from Turkey.

PMID- 9550683
TI  - Microscopic polyarteritis with antineutrophil cytoplasmic antibodies in
      polyglandular autoimmunity.

PMID- 9550684
TI  - Non-oliguric acute renal failure in non-fulminant acute viral hepatitis.

PMID- 9550685
TI  - Renal tolerance of combined treatment with foscarnet and indinavir.

PMID- 9550686
TI  - Paraoxonase activity stimulation by salts is higher in chronic renal failure
      patients than in controls.

PMID- 9550687
TI  - Subcutaneous erythropoietin alpha (Eprex) is more painful than erythropoietin
      beta (Recormon)

PMID- 9550688
TI  - Bilateral spontaneous avulsion of quadriceps tendons.

PMID- 9550689
TI  - Significant removal of phenytoin during high flux dialysis with cellulose
      triacetate dialyzer.

PMID- 9550690
TI  - Early mammals: teeth, jaws and finally a skeleton!
AB  - Suprising new fossils - a skeleton and a jaw - give us a much clearer picture of
      mammals that lived during the time of non-avian dinosaurs; the new finds
      illuminate the early evolution of the lineage leading to modern mammals, and
      challenge traditional understanding of placental mammal evolution and
      biogeography.

PMID- 9550692
TI  - Cortical organization: modules, polymaps and mosaics.
AB  - Recent studies of functional maps in the mammalian visual cortex fail to support
      the widespread belief that the cortex contains millimetre-sized modules; instead,
      they reveal a more fluid arrangement in which several separate maps are
      superimposed, with relatively weak geometric linkages and no common modular
      subunit.

PMID- 9550691
TI  - Olfactory processing: a time and place for everything.
AB  - The behavioral effects of pharmacologically desynchronizing neuronal firing in
      the brain of the honeybee provide new evidence that the oscillatory
      synchronization of neuronal activity plays an important role in fine olfactory
      discrimination.

PMID- 9550693
TI  - Gametogenesis: keeping the male element under control.
AB  - Caenorhabditis elegans hermaphrodites switch from making sperm to oocytes. This
      switch involves repression of fem-3 mRNA, mediated by a protein that binds RNA
      through a conserved motif; a similar motif mediates RNA binding by the Drosophila
      pattern-regulatory protein Pumilio.

PMID- 9550694
TI  - Stroke: a double-edged sword for cleaving clots?
AB  - The discovery that tissue plasminogen activator can promote neuronal degeneration
      has uncovered a novel pathway leading to neuronal cell death and raises important
      issues concerning the use of tissue plasminogen activator as a thrombolytic
      therapy for stroke.

PMID- 9550695
TI  - Mitochondrial import: crossing the aqueous intermembrane space.
AB  - Mitochondrial protein import follows a general pathway for preproteins with amino
      terminal presequences. The discovery of novel import components has now revealed
      a distinct pathway for translocation of hydrophobic proteins across the
      intermembrane space and into the inner membrane.

PMID- 9550696
TI  - Genomics: re-evaluation of translation machinery evolution.
AB  - Experiments based on genome sequence analysis have revealed unexpected complexity
      in the evolution of the translation apparatus, including concerted evolution of
      Gln-tRNA synthetase and Glu-tRNAGln amidotransferase, and a novel, class I Lys
      tRNA synthetase shared by archaea and spirochaetes.

PMID- 9550697
TI  - Tubulin family: kinship of key proteins across phylogenetic domains.
AB  - Atomic structures obtained by electron microscopy for tubulin, and by X-ray
      crystallography for bacterial FtsZ, show that the two proteins are highly
      homologous. The complementarity between such high-resolution studies and low
      resolution reconstructions of microtubule complexes is clear, but controversy
      still abounds.

PMID- 9550698
TI  - p27Kip1 alters the response of cells to mitogen and is part of a cell-intrinsic
      timer that arrests the cell cycle and initiates differentiation.
AB  - BACKGROUND: In many vertebrate cell lineages, precursor cells divide a limited
      number of times before they arrest and terminally differentiate into postmitotic
      cells. It is not known what causes them to stop dividing. We have been studying
      the 'stopping' mechanism in the proliferating precursor cells that give rise to
      oligodendrocytes, the cells that make myelin in the central nervous system. We
      showed previously that the cyclin-dependent kinase inhibitor p27Kip1 (p27)
      progressively accumulates in cultured precursor cells as they proliferate and
      that the time course of the increase is consistent with the possibility that p27
      accumulation is part of a cell-intrinsic timer that arrests the cell cycle and
      initiates differentiation at the appropriate time. RESULTS: We now provide direct
      evidence that p27 is part of the intrinsic timer. We show that although p27-/-
      precursor cells stop dividing and differentiate almost as fast as wild-type cells
      when deprived of mitogen, when stimulated by saturating amounts of mitogen they
      have a normal cell-cycle time but tend to go through one or two more divisions
      than wild-type cells before they stop and differentiate. Cells that are p27+/-
      behave in an intermediate way, going through at most one extra division,
      indicating that the levels of p27 matter in the way the timer works. We also show
      that p27-/- precursor cells are more sensitive than wild-type cells to the
      mitogenic effect of platelet-derived growth factor. CONCLUSIONS: These findings
      demonstrate that p27 is part of the normal timer that determines when
      oligodendrocyte precursor cells stop dividing and differentiate, at least in
      vitro. It seems likely that p27 plays a similar role in many other cell lineages,
      which could explain the phenotypes of the p27-/- and p27+/- mice.

PMID- 9550699
TI  - The DEAH-box splicing factor Prp16 unwinds RNA duplexes in vitro.
AB  - BACKGROUND: During pre-mRNA splicing, dynamic rearrangement of RNA secondary
      structure within the spliceosome is crucial for intron recognition and formation
      of the catalytic core. Splicing factors belonging to the DExD/DExH-box family of
      RNA-dependent ATPases are thought to have a central role in directing these
      rearrangements by unwinding RNA helices. Proof of this hypothesis has, however,
      been conspicuously lacking. RESULTS: Prp16 is a DEAH-box protein that functions
      in the second step of splicing in vitro. Using various RNA duplexes as substrate,
      we have shown that Prp16 has an ATP-dependent RNA unwinding activity. This
      activity is independent of sequence in either the single-stranded or duplexed
      regions of the RNA substrate. A mutation (prp16-1) near the ATP-binding motif of
      Prp16 inhibits both the RNA-dependent ATPase activity and the ATP-dependent RNA
      unwinding activity. CONCLUSIONS: Our findings provide strong biochemical evidence
      that Prp16 can disrupt a duplexed RNA structure on the spliceosome. Because the
      purified protein lacks sequence specificity in unwinding RNA duplexes, targeting
      of the unwinding activity of Prp16 in the spliceosome is likely to be determined
      by other interacting protein factors. The demonstration of unwinding activity
      will also help our understanding of how the fidelity of branchpoint recognition
      is controlled by Prp16.

PMID- 9550700
TI  - Evidence for two modes of cooperative DNA binding in vivo that do not involve
      direct protein-protein interactions.
AB  - BACKGROUND: The promoter regions of most eukaryotic genes contain binding sites
      for more than one transcriptional activator and these activators often bind
      cooperatively to promoters. The most common type of cooperativity is supported by
      direct protein-protein interactions. Recent studies have shown that proteins that
      do not specifically interact with one another can bind cooperatively to chromatin
      in vitro. probably by the localized destabilization of nucleosome structure by
      one factor, facilitating binding of another to a nearby site. This mechanism does
      not require that the transcription factors have activation domains. We have
      examined whether this phenomenon occurs in vivo. RESULTS: Unrelated non
      interacting proteins can bind DNA cooperatively in yeast cells; this cooperative
      binding can contribute significantly to transcriptional activation, does not
      require that both factors have activation domains and is only operative over
      relatively short distances. In addition to this 'short-range' mechanism,
      unrelated non-interacting proteins can bind cooperatively to sites separated by
      hundreds of base pairs, so long as both have potent activation domains.
      CONCLUSION: Cooperative binding of transcription factors in vivo can occur by
      several mechanisms, some of which do not require direct protein-protein
      interactions and which cannot be detected in vitro using naked DNA templates.
      These findings must be taken into account when evaluating mechanisms for
      synergistic transcriptional activation.

PMID- 9550701
TI  - Positional information in root epidermis is defined during embryogenesis and acts
      in domains with strict boundaries.
AB  - BACKGROUND: Cell position rather than cell lineage governs most aspects of
      development in plants. However, the nature and the origin of positional
      information remains elusive. Animal epidermal patterning relies in many cases on
      positional information provided by cell-cell communication. The epidermal layer
      of the Arabidopsis root is made of alternating files of two cell types and thus
      presents a simple pattern to study positional mechanisms. RESULTS: Clonal
      analysis of the root epidermis in combination with molecular and morphological
      markers has shown that cell fate is determined by position relative to the
      underlying cell layer, the cortex. The epidermal pattern appears to be organised
      during embryogenesis. Fate is not fixed in the developing root, though, as cells
      that move into a position previously occupied by neighbour cells ablated using
      laser microsurgery change fate. In contrast, cell fate is not altered when
      communication with living neighbour cells is impaired. Precise mapping of the
      influence of the position of extracellular cues on cell fate has shown that
      domains of positional information are organised with well-defined boundaries.
      CONCLUSIONS: Cell-fate specification in the root epidermis relies on positional
      information that is organised in stable domains with sharp boundaries. The
      epidermal pattern is defined during embryogenesis and positional information
      remains active in the root until the initiation of cell morphogenesis. The origin
      of some positional cues might be extracellular.

PMID- 9550702
TI  - Ras-dependent activation of the small GTPase Ral.
AB  - The small GTPase Ral is a Ras-like GTPase [1] that has been implicated in growth
      factor-induced and Ras-induced DNA synthesis [2-4], and Ras-induced oncogenic
      transformation [3,5]. Recently, we and others found that three different Ral
      guanine nucleotide exchange factors (Ral GEFs) - Ral GDS, Rgl and Rlf - bind
      specifically to the GTP-bound form of several Ras-like GTPases [6-9]. Although
      oncogenic Ras is able to activate these Ral GEFs [2,5,10], it is unknown whether
      growth factors can induce the activation of Ral and, if so, which small GTPase is
      involved in this process. Here, we show that stimulation of various growth factor
      receptors, including receptor tyrosine kinases and serpentine receptors, results
      in rapid activation of Ral. This activation correlates with the activation of
      Ras, and dominant-negative Ras completely inhibits Ral activation induced by
      insulin and epidermal growth factor (EGF). From these results, we conclude that
      Ral activation is a direct downstream effect of growth-factor-induced Ras
      activation.

PMID- 9550703
TI  - Insulin-dependent translocation of ARNO to the plasma membrane of adipocytes
      requires phosphatidylinositol 3-kinase.
AB  - ADP-ribosylation factors (ARFs) are small GTP-binding proteins that are
      regulators of vesicle trafficking in eukaryotic cells [1]. ARNO is a member of
      the family of guanine nucleotide exchange factors for ARFs which includes
      cytohesin-1 and GRP-1 [2] [3-5]. Members of this family contain a carboxy
      terminal pleckstrin homology (PH) domain which, in the case of GRP-1, has been
      shown to bind the second messenger phosphatidylinositol 3,4,5-trisphosphate
      (PIP3) in preference to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and
      phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) in vitro [3,4]. Here, we show
      that recombinant ARNO has the binding characteristics of a PIP3 receptor and that
      this activity is restricted to the PH domain. When expressed in murine 3T3 L1
      adipocytes, ARNO tagged using green fluorescent protein (GFP) is localised
      exclusively in the cytoplasm. Stimulation with insulin, however, causes a rapid
      (< 50 second) PH-domain-dependent translocation of GFP-ARNO to the plasma
      membrane. This translocation is blocked by the PI(4,5)P2 3-kinase (PI 3-kinase)
      inhibitors wortmannin and LY294002, and by co-expression with a dominant-negative
      p85 mutant, suggesting that the translocation is a consequence of insulin
      stimulation of PI 3-kinase. Our data strongly suggest that ARNO binds PIP3 in
      vivo and that this interaction causes a translocation of ARNO to the plasma
      membrane where it might activate ARF6 and regulate subsequent plasma membrane
      cycling events.

PMID- 9550704
TI  - p53-dependent impairment of T-cell proliferation in FADD dominant-negative
      transgenic mice.
AB  - Members of the tumour necrosis factor (TNF) receptor family exert pleiotropic
      effects and can trigger both apoptosis and proliferation [1]. In their
      cytoplasmic region, some of these receptors share a conserved sequence motif -
      the 'death domain' - which is required for transduction of the apoptotic signal
      by recruiting other death-domain-containing adaptor molecules like the Fas
      associated protein FADD/MORT1 or the TNF receptor-associated protein TRADD [2-4].
      FADD links the receptor signal to the activation of the caspase family of
      cysteine proteases [5,6]. Functional inactivation of individual receptor family
      members often fails to exhibit a distinctive phenotype, probably because of
      redundancy [7-9]. To circumvent this problem, we used a dominant-negative mutant
      of FADD (FADD-DN) which should block all TNF receptor family members that use
      FADD as an adaptor. We established transgenic mice expressing FADD-DN under the
      influence of the lck promoter and investigated the consequences of its expression
      in T cells. As expected, FADD-DN thymocytes were protected from death induced by
      CD95 (Fas/Apo1), whereas apoptosis induced by ultraviolet (UV) irradiation, anti
      CD3 antibody treatment or dexamethasone was unaffected, as was spontaneous cell
      death. Surprisingly, however, we also observed profound inhibition of thymocyte
      proliferation in vivo and of activation-induced proliferation of thymocytes and
      mature T cells in vitro. This inhibition of proliferation was not due to
      increased cell death and appeared to be p53 dependent.

PMID- 9550705
TI  - Cooperation of intrinsic and extrinsic signals in the elaboration of regional
      identity in the posterior cerebral cortex.
AB  - Understanding the compartmentalization of the neocortex (isocortex) of the
      mammalian brain into functional areas is a challenging problem [1-3] . Unlike
      pattern formation in the spinal cord and hindbrain, it does not involve the
      specification of distinct cells types: distinct areas differ in their patterns of
      connectivity and cytoarchitecture. It has been suggested that signals intrinsic
      to the neocortical neuroepithelium specify regional fate [3]. Alternatively,
      spatial patterning might be imposed by extrinsic cues such as thalamocortical
      projections [4-6]. Recent results highlight the ability of early precursor cells
      of the telencephalic neuroepithelium to 'remember' their spatial position from
      times before thalamic innervation [7,8] [9-12]. An influence from the thalamus,
      however, cannot be ruled out as there is a precise invasion of the correct
      cortical areas by the corresponding projections [13,14]. Furthermore, cortical
      neuronal progenitors have been proposed to adopt new connection patterns after
      transplantation [6,7], as well as when the thalamic input is rerouted [15,16].
      Here, we describe the transient expression of the homeobox gene Otx2 in the
      posterior, prospective visual, neocortex and use it to analyze the establishment
      of posterior cortical fate. The results suggest that whereas intrinsic cortical
      information is sufficient to specify regional fate, extrinsic signals from the
      thalamus are involved in the expansion or maintenance of the population of cells
      expressing Otx2 but not in regionalization.

PMID- 9550707
TI  - Kim nasmyth: the universal truth 

PMID- 9550706
TI  - Regulation of gene expression is preserved in aging Drosophila melanogaster.
AB  - Aging, and the deterioration of biological performance that characterizes it, are
      routinely assumed to be due to a progressive global loss of homeostasis and a
      general increase in dysregulation [1-4] . We tested this hypothesis directly by
      measuring age-specific variability in gene expression. Analysis of the
      transcriptional activity of six genes in various inbred lines of Drosophila
      melanogaster unexpectedly failed to show an increase in variability among
      individuals as they age and die. Although regulation of gene expression is a
      central feature of life, a global decline in the control of gene expression does
      not appear to be either a cause or a consequence of the process of aging.

PMID- 9550709
TI  - Get alife 

PMID- 9550708
TI  - The knowledge industry 

PMID- 9550711
TI  - Hypersensitive fish 

PMID- 9550710
TI  - The complement system.

PMID- 9550712
TI  - Continuing organizer function during chick tail development.
AB  - Development of the posterior body (lumbosacral region and tail) in vertebrates is
      delayed relative to gastrulation. In amniotes, it proceeds with the replacement
      of the regressed node and primitive streak by a caudal blastema-like mass of
      mesenchyme known as the tail bud. Despite apparent morphological dissimilarities,
      recent results suggest that tail development in amniotes is in essence a
      continuation of gastrulation, as is the case in Xenopus. However, this has been
      inferred primarily from the outcome of fate mapping studies demonstrating
      discrete, regionalized cell populations in the tail bud, like those present at
      gastrulation. Our analysis of the tail bud distribution of several molecular
      markers that are expressed in specific spatial domains during chick gastrulation
      confirms these results. Furthermore, we present evidence that gastrulation-like
      ingression movements from the surface continue in the early chick tail bud and
      that the established tail bud retains organizer activity. This 'tail organizer'
      has the expected properties of being able to recruit uncommitted host cells into
      a new embryonic axis and induce host neural tissue with posteriorly regionalized
      gene expression when grafted to competent host cells that are otherwise destined
      to form only extra-embryonic tissue. Together, these results indicate that chick
      tail development is mechanistically continuous with gastrulation and that the
      developing tail in chick may serve as a useful experimental adjunct to
      investigate the molecular basis of inductive interactions operating during
      gastrulation, considering that residual tail organizing activity is still present
      at a surprisingly late stage.

PMID- 9550713
TI  - Genetic regulation of entry into meiosis in Caenorhabditis elegans.
AB  - The Caenorhabditis elegans germline is composed of mitotically dividing cells at
      the distal end that give rise to meiotic cells more proximally. Specification of
      the distal region as mitotic relies on induction by the somatic distal tip cell
      and the glp-1 signal transduction pathway. However, the genetic control over the
      transition from mitosis to meiosis is not understood. In this paper, we report
      the identification of a gene, gld-2, that has at least two functions in germline
      development. First, gld-2 is required for normal progression through meiotic
      prophase. Second, gld-2 promotes entry into meiosis from the mitotic cell cycle.
      With respect to this second function, gld-2 appears to be functionally redundant
      with a previously described gene, gld-1 (Francis, R., Barton, M. K., Kimble, J.
      and Schedl, T. (1995) Genetics 139, 579-606). Germ cells in gld-1(o) and gld-2
      single mutants enter meiosis at the normal time, but germ cells in gld-2 gld-1(o)
      double mutants do not enter meiosis. Instead, the double mutant germline is
      mitotic throughout and forms a large tumor. We suggest that gld-1 and gld-2
      define two independent regulatory pathways, each of which can be sufficient for
      entry into meiosis. Epistasis analyses show that gld-1 and gld-2 work downstream
      of the glp-1 signal transduction pathway. Therefore, we hypothesize that glp-1
      promotes proliferation by inhibiting the meiosis-promoting functions of gld-1 and
      gld-2.

PMID- 9550714
TI  - Bundle sheath cells and cell-specific plastid development in Arabidopsis leaves.
AB  - Bundle sheath cells form a sheath around the entire vascular tissue in
      Arabidopsis leaves and constitute a distinct leaf cell type, as defined by their
      elongate morphology, their position adjacent to the vein and by differences in
      their chloroplast development compared to mesophyll cells. They constitute about
      15% of chloroplast-containing cells in the leaf. In order to identify genes which
      play a role in the differential development of bundle sheath and mesophyll cell
      chloroplasts, a screen of reticulate leaf mutants of Arabidopsis was used to
      identify a new class of mutants termed dov (differential development of vascular
      associated cells). The dov1 mutant clearly demonstrates a cell-specific
      difference in chloroplast development. Mutant leaves are highly reticulate with a
      green vascular pattern. The underlying bundle sheath cells always contain normal
      chloroplasts, whereas chloroplasts in mesophyll cells are abnormal, reduced in
      number per cell and seriously perturbed in morphology at the ultrastructural
      level. This demonstrates that differential chloroplast development occurs between
      the bundle sheath and mesophyll cells in the Arabidopsis leaf.

PMID- 9550715
TI  - Genetic interactions and cell behaviour in blistered mutants during proliferation
      and differentiation of the Drosophila wing.
AB  - In this work, we analyse the blistered function in wing vein development by
      studying genetic mosaics of mutant cells, genetic interactions with other genes
      affecting vein development and blistered expression in several mutant
      backgrounds. blistered encodes for a nuclear protein homologous to the mammalian
      Serum Response Factor and is expressed in presumptive intervein cells of third
      larval instar and pupal wing discs. Clones of blistered mutant cells proliferate
      normally but tend to grow along veins and always differentiate as vein tissue.
      These observations indicate that vein-determined wing cells show a particular
      behaviour that is responsible for their allocation to vein regions. We observe
      strong genetic interactions between blistered, veinlet and genes of the Ras
      signaling cascade. During disc proliferation, blistered expression is under the
      control of the Ras signal transduction pathway, but its expression is independent
      of veinlet. During the pupal period, blistered and veinlet expression become
      interdependent and mutually exclusive. These results link the activity of the Ras
      pathway to the process of early determination of intervein cells, by the
      transcriptional control of the blistered nuclear factor.

PMID- 9550716
TI  - Genetic dissection of sperm individualization in Drosophila melanogaster.
AB  - The morphogenesis of spermatids generally takes place within a syncytium, in
      which all spermatid nuclei descended from a primary spermatocyte remain connected
      via an extensive network of cytoplasmic bridges. A late step in sperm maturation
      therefore requires the physical resolution of the syncytium, or cyst, into
      individual cells, a process sometimes referred to as sperm individualization.
      Despite the identification of specialized machinery involved in the
      individualization of Drosophila spermatids (Tokuyasu, K. T., Peacock, W. J. and
      Hardy, R. W. (1972) Z. Zellforsch 124, 479-506), and of many Drosophila genes
      mutable to male-sterile phenotypes, little is known of the mechanisms by which
      this extensive remodeling of the cyst is accomplished. Here, the identification
      of a major cytoskeletal component of the individualization complex as actin is
      confirmed with a simple fluorescence assay. Using rhodamine-phalloidin as a
      probe, the individualization complex is readily visualized forming around bundles
      of spermatid nuclei at one end of highly elongated cysts, then translocating
      along the length of the cysts. The structure of the individualization complex in
      a male-sterile clathrin heavy chain (Chc) mutant is observed to be reduced or
      disrupted relative to wild-type, consistent with the individualization-deficient
      phenotype of this mutant. Using the fluorescence assay, a sampling of male
      sterile mutant phenotypes in which spermatogenesis proceeds to the assembly of
      highly elongated cysts distinguishes at least four different phenotypic classes:
      (1) mutations (nanking class) that block or significantly retard the assembly of
      the actin-based individualization complex around the nuclear bundle, (2)
      mutations (dud class) in which the individualization complex assembles in/around
      the nuclear bundle, but fails to translocate down the cyst, (3) mutations (mulet
      class) that allow the assembly of a morphologically normal individualization
      complex around the nuclear bundle, but result in a breakdown in the complex after
      it begins to translocate down the cyst, and (4) mutations (purity of essence
      class) that allow the assembly of a motile but morphologically altered or reduced
      individualization complex. Individualization also fails in a number of mutants
      with altered nuclear shape, consistent with the hypothesis that spermatid nuclei
      provide a physical scaffolding for the assembly of the individualization complex.
      Genetic analysis suggests that a substantial number of additional loci with
      phenotypes distinguishable with this assay remain to be identified. The large
      proportion of male-sterile mutations resulting in a late block to
      spermatogenesis, in which highly elongated cysts fail to be individualized,
      suggest a substantial susceptibility of this process to a broad range of cellular
      perturbations. The massive reorganization of cyst cytoplasm required at
      individualization is expected to be a correspondingly complex function requiring
      exquisite coordination of multiple cytoplasmic functions, and may account for the
      previously noted high frequency with which Drosophila genes are mutable to male
      sterile phenotypes.

PMID- 9550717
TI  - The Drosophila sanpodo gene controls sibling cell fate and encodes a tropomodulin
      homolog, an actin/tropomyosin-associated protein.
AB  - Notch signaling is required in many invertebrate and vertebrate cells to promote
      proper cell fate determination. Mutations in sanpodo cause many different
      neuronal peripheral nervous system precursor cells to generate two identical
      daughter neurons, instead of a neuron and sibling cell. This phenotype is similar
      to that observed when Notch function is lost late in embryonic development and
      opposite to the numb loss-of-function phenotype. Genetic interaction studies show
      that sanpodo is epistatic to numb. sanpodo encodes a homolog of tropomodulin, an
      actin/tropomyosin-associated protein. Loss of sanpodo leads to an aberrant F
      actin distribution and causes differentiation defects of actin-containing sensory
      structures. Our data suggest that an actin-based process is involved in Notch
      signaling.

PMID- 9550718
TI  - Sanpodo and Notch act in opposition to Numb to distinguish sibling neuron fates
      in the Drosophila CNS.
AB  - In Drosophila, most neuronal siblings have different fates ('A/B'). Here we
      demonstrate that mutations in sanpodo, a tropomodulin actin-binding protein
      homologue, equalize a diverse array of sibling neuron fates ('B/B'). Loss of
      Notch signaling gives the same phenotype, whereas loss of numb gives the opposite
      phenotype ('A/A'). The identical effect of removing either sanpodo or Notch
      function on the fates of sibling CNS neurons indicates that sanpodo may act in
      the Notch signaling pathway. In addition, sanpodo and numb show dosage-sensitive
      interactions and epistasis experiments indicate that sanpodo acts downstream of
      numb. Taken together, these results show that interactions between sanpodo, the
      Notch signaling pathway and numb enable CNS sibling neurons to acquire different
      fates.

PMID- 9550719
TI  - Tbx genes and limb identity in chick embryo development.
AB  - Tbx-2, Tbx-3, Tbx-4 and Tbx-5 chick genes have been isolated and, like the mouse
      homologues, are expressed in the limb regions. Tbx-2 and Tbx-3 are expressed in
      anterior and posterior domains in wings and legs, as well as throughout the
      flank. Of particular interest, however, are Tbx-5, which is expressed in wing and
      flank but not leg, and Tbx-4, which is expressed very strongly in leg but not
      wing. Grafts of leg tissue to wing and wing tissue to leg give rise to toe-like
      or wing-like digits in wing and leg respectively. Expression of Tbx-4 is stable
      when leg tissue is grafted to wing, and Tbx-5 expression is stable when wing
      tissue is grafted to leg. Induction of either extra wings or legs from the flank
      by applying FGF-2 in different positions alters the expression of Tbx-4 and Tbx-5
      in such a way that suggests that the amount of Tbx-4 that is expressed in the
      limb determines the type that will form. The ectopic limb always displays a limb
      like Tbx-3 expression. Thus Tbx-4 and Tbx-5 are strong candidates for encoding
      'wingness' and 'legness'.

PMID- 9550720
TI  - The Tlx-2 homeobox gene is a downstream target of BMP signalling and is required
      for mouse mesoderm development.
AB  - TGFbeta-related factors are critical regulators of vertebrate mesoderm
      development. However, the signalling cascades required for their function during
      this developmental process are poorly defined. Tlx-2 is a homeobox gene expressed
      in the primitive streak of mouse embryos. Exogenous BMP-2 rapidly activates Tlx-2
      expression in the epiblast of E6.5 embryos. A Tlx-2 promoter element responds to
      BMP-2 signals in P19 cells, and this response is mediated by BMP type I receptors
      and Smad1. These results suggest that Tlx-2 is a downstream target gene for BMP
      signalling in the primitive streak where BMP-4 and other TGFbeta-related factors
      are expressed. Furthermore, disruption of Tlx-2 function leads to early embryonic
      lethality. Similar to BMP4 and ALK3 mutants, the mutant embryos display severe
      defects in primitive streak and mesoderm formation. These experiments thus define
      a BMP/Tlx-2 signalling pathway that is required during early mammalian
      gastrulation.

PMID- 9550721
TI  - HASTY: a gene that regulates the timing of shoot maturation in Arabidopsis
      thaliana.
AB  - In Arabidopsis thaliana, leaves produced at different stages of shoot development
      can be distinguished by the distribution of trichomes on the abaxial and adaxial
      surfaces. Leaves produced early in the development of the rosette (juvenile
      leaves) have trichomes on their adaxial, but not their abaxial surface, whereas
      leaves produced later in rosette development (adult leaves) have trichomes on
      both surfaces. In order to identify genes that regulate the transition between
      these developmental phases we screened for mutations that accelerate the
      production of leaves with abaxial trichomes. 9 alleles of the HASTY gene were
      recovered in this screen. In addition to accelerating the appearance of adult
      leaves these mutations also accelerate the loss of adaxial trichomes (a trait
      typical of bracts), reduce the total number of leaves produced by the shoot, and
      have a number of other effects on shoot morphology. The basis for this phenotype
      was examined by testing the interaction between hasty and genes that affect
      flowering time (35S::LEAFY, 35S::APETALA1, terminal flower1), gibberellin
      production (ga1-3) or perception (gai), and floral morphogenesis (leafy,
      apetala1, agamous). We found that hasty increased the reproductive competence of
      the shoot, and that its does not require gibberellin or a gibberellin response
      for its effect on vegetative or reproductive development. The phenotype of hasty
      is not suppressed by leafy, apetala1 and agamous, demonstrating that this
      phenotype does not result from the inappropriate expression of these genes. We
      suggest that HASTY promotes a juvenile pattern of vegetative development and
      inhibits flowering by reducing the competence of the shoot to respond to LEAFY
      and APETALA1.

PMID- 9550722
TI  - Selective disruption of neuregulin-1 function in vertebrate embryos using
      ribozyme-tRNA transgenes.
AB  - The products of the neuregulin-1 gene constitute a set of polypeptide growth
      factors whose signalling through the ErbB receptors is essential to the growth
      and differentiation of many cell types in culture. Although studies with
      neuregulin-1 mutant mice have demonstrated that these growth factors are also
      essential regulators of cellular differentiation in vivo, the mid-embryonic death
      of these mutants precludes an analysis of hypothesized neuregulin-1 roles in
      later aspects of development. To circumvent this early lethality, we have pursued
      a ribozyme-based strategy for the perturbation of neuregulin-1 function in
      developing chick embryos. Early administration of a retrovirus carrying
      neuregulin-1 hammerhead-type ribozymes to blastoderm-stage embryos leads to an
      embryonic lethal phenotype that results from the failure of ventricular
      trabeculation in the developing heart, a faithful phenocopy of the mouse
      neuregulin-1 mutations. Later, more localized delivery of the ribozyme to the
      developing retina inhibits both the differentiation of retinal ganglion cell
      neurons and the proliferation of the neuroepithelial cells from which they
      derive. These results suggest that neuregulin-1 promotes both muscle cell
      differentiation in the heart and neuronal differentiation in the central nervous
      system. In addition, they demonstrate the utility of hammerhead ribozymes as a
      simple, effective and easily adaptable method of conditional gene inactivation in
      vertebrates.

PMID- 9550723
TI  - A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis.
AB  - In the Drosophila larva, blood cells or hemocytes are formed in the lymph gland.
      The major blood cell type, called plasmatocyte, is small, non-adhesive and
      phagocytic. Plasmatocytes differentiate into adhesive lamellocytes to form
      multilayered capsules around foreign substances or, in mutant melanotic tumor
      strains, around self tissue. Mutations in cactus or Toll, or constitutive
      expression of dorsal can induce lamellocyte differentiation and cause the
      formation of melanotic capsules. As maternally encoded proteins, Toll, Cactus and
      Dorsal, along with Tube and Pelle, participate in a common signal transduction
      pathway to specify the embryonic dorsal-ventral axis. Using the maternal pathway
      as a paradigm, we investigated if these proteins have additional roles in larval
      hemocyte formation and differentiation. Analysis of cactus mutants that lack
      Cactus protein revealed that almost all of these animals have an overabundance of
      hemocytes, carry melanotic capsules and die before reaching pupal stages. In
      addition, the lymph glands of cactus larvae are considerably enlarged. The number
      of mitotic cells in the cactus and TollD hemolymph is higher than that in the
      wild-type hemolymph. The hemocyte density of mutant Toll, tube or pelle hemolymph
      is significantly lower than that of the wild type. Lethality of mutant cactus
      animals could be rescued either by the selective expression of wild-type Cactus
      protein in the larval lymph gland or by the introduction of mutations in Toll,
      tube or pelle. Cactus, Toll, Tube and Pelle proteins are expressed in the nascent
      hemocytes of the larval lymph gland. Our results suggest that the Toll/Cactus
      signal transduction pathway plays a significant role in regulating hemocyte
      proliferation and hemocyte density in the Drosophila larva. These findings are
      discussed in light of similar hematopoietic functions of Rel/I(kappa)B-family
      proteins in mice.

PMID- 9550724
TI  - An entire functional mammary gland may comprise the progeny from a single cell.
AB  - Any epithelial portion of a normal mouse mammary gland can reproduce an entire
      functional gland when transplanted into an epithelium-free mammary fat pad. Mouse
      mammary hyperplasias and tumors are clonal dominant populations and probably
      represent the progeny of a single transformed cell. Our study provides evidence
      that single multipotent stem cells positioned throughout the mature fully
      developed mammary gland have the capacity to produce sufficient differentiated
      progeny to recapitulate an entire functional gland. Our evidence also
      demonstrates that these stem cells are self-renewing and are found with
      undiminished capacities in the newly regenerated gland. We have taken advantage
      of an experimental model where mouse mammary tumor virus infects mammary
      epithelial cells and inserts a deoxyribonucleic acid copy(ies) of its genome
      during replication. The insertions occur randomly within the somatic genome.
      CzechII mice have no endogenous nucleic acid sequence homology with mouse mammary
      tumor virus; therefore all viral insertions may be detected by Southern analysis
      provided a sufficient number of cells contain a specific insertional event.
      Transplantation of random fragments of infected CzechII mammary gland produced
      clonal-dominant epithelial populations in epithelium-free mammary fat pads.
      Serial transplantation of pieces of the clonally derived outgrowths produced
      second generation glands possessing the same viral insertion sites providing
      evidence for self-renewal of the original stem cell. Limiting dilution studies
      with cell cultures derived from third generation clonal outgrowths demonstrated
      that three multipotent but distinct mammary epithelial progenitors were present
      in clonally derived mammary epithelial populations. Estimation of the potential
      number of multipotent epithelial cells that may be evolved from an individual
      mammary-specific stem cell by self-renewal is in the order of 10(12)-10(13).
      Therefore, one stem cell might easily account for the renewal of mammary
      epithelium over several transplant generations.

PMID- 9550725
TI  - Patterns and control of cell motility in the Xenopus gastrula.
AB  - By comparing cells with respect to several motility-related properties and the
      ability to migrate on fibronectin, three cell types can be distinguished in the
      Xenopus gastrula. These occur in a distinct spatial pattern, thus defining three
      motility domains which do not correspond to the prospective germ layers.
      Migratory behavior is confined to a region encompassing the anterior mesoderm and
      endoderm. When stationary animal cap cells are induced to migrate by treatment
      with activin, cells become adhesive at low concentrations of fibronectin, show
      polarized protrusive activity, and form lamellipodia. Adhesion and polarization,
      but not lamellipodia formation, are mimicked by the immediate early response gene
      Mix.1. Goosecoid, another immediate early gene, is without effect when expressed
      alone in animal cap cells, but it acts synergistically with Mix.1 in the control
      of adhesion, and antagonistically in the polarization of protrusive activity.
      bFGF also induces migration, lamellipodia formation and polarization in animal
      cap cells, but has no effect on adhesion. By the various treatments of animal cap
      cells, new combinations of motile properties can be generated, yielding cell
      types which are not found in the embryo.

PMID- 9550726
TI  - Ventricular muscle-restricted targeting of the RXRalpha gene reveals a non-cell
      autonomous requirement in cardiac chamber morphogenesis.
AB  - Mouse embryos lacking the retinoic acid receptor gene RXR(alpha) die in
      midgestation from hypoplastic development of the myocardium of the ventricular
      chambers and consequent cardiac failure. In this study, we address the issue of
      whether the RXRalpha gene is required in the cardiomyocyte lineage by generating
      mice that harbor a ventricular restricted deficiency in RXRalpha at the earliest
      stages of ventricular chamber specification. We first created a conditional
      ('floxed') allele of RXRalpha by flanking a required exon of the gene with loxP
      recombination sequences. To achieve ventricular myocardium-specific gene
      targeting, and to avoid potential transgenic artifacts, we employed a knock-in
      strategy to place cre recombinase coding sequences into the myosin light chain 2v
      (MLC2v) genomic locus, a gene which in the heart is expressed exclusively in
      ventricular cardiomyocytes at the earliest stages of ventricular specification.
      Crossing the MLC2v-cre allele with the floxed RXRalpha gene resulted in embryos
      in which approximately 80% of the ventricular cardiomyocytes lacked RXRalpha
      function, and yet which displayed a completely normal phenotype, without evidence
      of the wide spectrum of congenital heart disease phenotype seen in RXRa-/-
      embryos, and normal adult viability. We conclude that the RXRalpha mutant
      phenotype is not cell autonomous for the cardiomyocyte lineage, and suggest that
      RXRalpha functions in a neighboring compartment of the developing heart to
      generate a signal that is required for ventricular cardiomyocyte development and
      chamber maturation.

PMID- 9550727
TI  - The RXRalpha gene functions in a non-cell-autonomous manner during mouse cardiac
      morphogenesis.
AB  - Germline mutation in mice of the retinoic acid receptor gene RXRalpha results in
      a proliferative failure of cardiomyocytes, which leads to an underdeveloped
      ventricular chamber and midgestation lethality. Mutation of the cell cycle
      regulator N-myc gene also leads to an apparently identical phenotype. In this
      study, we demonstrate by chimera analysis that the cardiomyocyte phenotype in
      RXRalpha-/- embryos is a non-cell-autonomous phenotype. In chimeric embryos made
      with embryonic stem cells lacking RXRalpha, cardiomyocytes deficient in RXRalpha
      develop normally and contribute to the ventricular chamber wall in a normal
      manner. Because the ventricular hypoplastic phenotype reemerges in highly
      chimeric embryos, we conclude that RXRalpha functions in a non-myocyte lineage of
      the heart to induce cardiomyocyte proliferation and accumulation, in a manner
      that is quantitatively sensitive. We further show that RXRalpha is not epistatic
      to N-myc, and that RXRalpha and N-myc regulate convergent obligate pathways of
      cardiomyocyte maturation.

PMID- 9550728
TI  - Initial anteroposterior pattern of the zebrafish central nervous system is
      determined by differential competence of the epiblast.
AB  - Analyses using amphibian embryos proposed that induction and anteroposterior
      patterning of the central nervous system is initiated by signals that are
      produced by the organizer and organizer-derived axial mesoderm. However, we show
      here that the initial anteroposterior pattern of the zebrafish central nervous
      system depends on the differential competence of the epiblast and is not imposed
      by organizer-derived signals. This anteroposterior information is present
      throughout the epiblast in ectodermal cells that normally give rise both to
      neural and non-neural derivatives. Because of this information, organizer tissues
      transplanted to the ventral side of the embryo induce neural tissue but the
      anteroposterior identity of the induced neural tissue is dependent upon the
      position of the induced tissue within the epiblast. Thus, otx2, an anterior
      neural marker, was only ever induced in anterior regions of the embryo,
      irrespective of the position of the grafts. Similarly, hoxa-1, a posterior neural
      marker was induced only in the posterior regions. Furthermore, the boundary of
      each ectopic expression domain on the ventral side was always at an equivalent
      latitude to that of the endogenous expression of the dorsal side of the embryo.
      The anteroposterior specification of the epiblast is independent of the
      dorsoventral specification of the embryo because neural tissues induced in the
      ventralized embryos also showed anteroposterior polarity. Cell transplantation
      and RNA injection experiments showed that non-axial marginal mesoderm and FGF
      signalling is required for anteroposterior specification of the epiblast.
      However, the requirement for FGF signalling is indirect in that cells with
      compromised ability to respond to FGF can still respond to anteroposterior
      positional information.

PMID- 9550729
TI  - A role for SOX1 in neural determination.
AB  - In vertebrates, the delineation of the neural plate from a region of the
      primitive ectoderm is accompanied by the onset of specific gene expression which
      in turn promotes the formation of the nervous system. Here we show that SOX1, an
      HMG-box protein related to SRY, is one of the earliest transcription factors to
      be expressed in ectodermal cells committed to the neural fate: the onset of
      expression of SOX1 appears to coincide with the induction of neural ectoderm. We
      demonstrate a role for SOX1 in neural determination and differentiation using an
      inducible expression P19 cell system as an in vitro model of neurogenesis.
      Misexpression of SOX1 can substitute for the requirement of retinoic acid to
      impart neural fate to competent ectodermal P19 cells. Using a series of antigenic
      markers which identify early neural cell types in combination with BrdU labeling,
      we demonstrate a temporal and spatial correlation between the differentiation of
      cell types along the dorsoventral axis of the neural tube and the downregulation
      of SOX1 expression. SOX1, therefore, defines the dividing neural precursors of
      the embryonic central nervous system (CNS).

PMID- 9550730
TI  - Monograph series on aging-related diseases: X. Prostate cancer.
AB  - Prostate cancer is the most commonly diagnosed cancer among Canadian men,
      excluding non-melanoma skin cancer. Prostate cancer incidence increases almost
      exponentially with age; most cases are diagnosed in men aged 65 years or older.
      With the possible exception of animal fat consumption, no known widespread
      modifiable risk factors have been identified. Although the prognosis is good if
      appropriate treatment occurs in the early stages of disease, the ability of
      existing early detection techniques to decrease mortality has not yet been
      demonstrated. The considerable economic and societal burden of prostate cancer
      and its treatment, coupled with the projected large increase in the number of new
      prostate cancer cases as the population ages, make this disease a very important
      public health issue.

PMID- 9550731
TI  - Pap smear utilization in Canada: estimates after adjusting the eligible
      population for hysterectomy status.
AB  - The 1994 National Population Health Survey (NPHS) confirmed that the trend in Pap
      smear utilization has not changed in the past 10 years; 15% of Canadian women
      reported never having had a Pap smear and an additional 15% reported not having
      had one within 3 years prior to the survey. Most of these underserved women can
      be characterized as disadvantaged. The overall prevalence of hysterectomy in
      Canada in 1994 was 16.3%, and prevalence increased sharply to 30% between ages 35
      and 55 years. Hysterectomy rates vary according to sociodemographic factors, with
      women of lower income and education indicating a higher proportion of
      hysterectomies. We adjusted the female population from the NPHS, by removing the
      estimated proportion of women reporting hysterectomy, to reveal the true
      population at risk of developing cervical cancer. Absolute prevalence of Pap
      smear utilization increased (7 - 25%); the relative improvement was much higher.
      Adjusting the eligible population could enable screening programs to better
      estimate the size of their underserved population.

PMID- 9550732
TI  - Firearms regulation: Canada in the international context.
AB  - Gun deaths and injuries in Canada are a serious public health problem, claiming
      more than 1200 lives each year and resulting in over 1000 hospitalizations. While
      the issue has been hotly debated in recent years, considerable research in an
      international context suggests that there is a relationship between access to
      firearms and deaths and injuries caused by firearms. Interventions to reduce
      access to firearms include regulation, education and engineering. Legislative
      reforms aimed at reducing gun deaths and injuries have been introduced recently
      in Canada and in many other countries. Although domestic controls can affect the
      supply of guns, efforts are being co-ordinated increasingly on an
      interjurisdictional basis to decrease the illegal trafficking of firearms. As
      well, the United Nations Crime Prevention and Criminal Justice Commission
      recently passed a resolution encouraging all countries who have not done so to
      strengthen their domestic gun controls since weak controls in one country can
      affect security in others.

PMID- 9550734
TI  - [Joint decisions, how? Physician-patient communication about palliative
      chemotherapy].
AB  - The discomfort and benefits of a medical treatment may be appreciated differently
      by different patients. This is one of the reasons why patients should be informed
      thoroughly and included in the decision-making about treatment. The obligation to
      inform was laid down in 1995 in the Decree on the Medical Contract. In a case of
      metastasized cancer of the prostate it was decided more or less by mutual
      agreement between doctor and patient to administer palliative chemotherapy. It
      appeared subsequently that the physician had short-term palliation in mind, and
      the patient prolongation of survival. Although both are of the opinion that the
      patient was included actively in the decision-making, this was in reality not at
      all the case. The question arises whether the Decree on the Medical Contract does
      not demand too much from certain patients regarding their capacity to make a
      decision about the treatment of a terminal disease.

PMID- 9550735
TI  - ['Public Health Status Forecasting 1997': the sum of the parts].
AB  - The 1997 edition of Public Health Status and Forecasts, a comprehensive
      epidemiological overview of the health of the Dutch nation, suggests some
      important new strategies for the development of a more 'evidence-based health
      policy'. The growing gap between life expectancy in general and healthy life
      expectancy demands a stronger effort in the prevention of unhealthy lifestyles,
      especially smoking. Many indicators of health show the first signs of decline for
      the coming 10-20 years. The growing burden of chronic diseases and longlasting
      handicaps points towards a doubling of the present yearly rise in the health
      budget to at least 2%. Methodological innovations in measuring health effects are
      a striking feature of the 1997 'explorations' report.

PMID- 9550733
TI  - The supercoiling sensitivity of a bacterial tRNA promoter parallels its
      responsiveness to stringent control.
AB  - In Salmonella typhimurium, expression of the hisR locus, a tRNA operon, decreases
      upon inhibiting DNA gyrase. Here, the hisR promoter dependence on negative DNA
      supercoiling was examined in vivo and in vitro. Mutant analysis showed the
      sequence determinants of this dependence to lie in the region between the -10 box
      and the transcription start site. As with most promoters subject to stringent
      control, this portion of the hisR promoter is C-G-rich. Replacing a C/G bp with
      T/A at position -7 partially relieves the supercoiling response while changing
      the sequence between -5 and + 1 (-CCCCCG-) for -GTTAA- abolishes the response in
      vitro and in vivo. The relief of the supercoiling dependence closely correlates
      with increased promoter susceptibility to melting in vivo and a lesser
      requirement for initiating nucleotides in the formation of stable initiation
      complexes in vitro. Studies in isoleucine-starved cells showed that such sequence
      changes mitigate and abolish the hisR promoter response to stringent control,
      respectively. The data presented suggest that the hisR promoter's sensitivity to
      stringent regulation arises from the same physical property that confers
      supercoiling sensitivity, i.e. resistance to melting. We propose that the
      stringent control mechanism acts by hampering the ability of RNA polymerase to
      melt the DNA helix.

PMID- 9550736
TI  - [Developments in the treatment of patients with chronic myeloid leukemia].
AB  - In the treatment of chronic myelocytic leukaemia (CML) allogeneic bone marrow
      transplantation (BMT) from a sibling donor is the treatment of choice in patients
      younger than 50 years; the overall 5-year survival is about 60%. Donor lymphocyte
      infusion without chemotherapy may serve as an efficacious therapy for recurrence
      of CML after allogeneic BMT. Application of allogeneic BMT from a matched
      unrelated donor is increasing, but the outcome is still inferior to that of
      sibling BMT, largely due to more severe and more frequent complications.
      Treatment with interferon-alpha has been shown to prolong the overall median
      survival, but especially in a subgroup of patients (about 15%) who achieve a
      major cytogenic response. Combination of interferon-alpha and low-dose cytarabine
      leads to increased survival and a better cytogenic response than interferon-alpha
      alone. Current investigations are aimed at further improving survival and
      cytogenic response by using more intensive chemotherapy, such as high-dose
      cytarabine, followed by interferon-alpha maintenance therapy.

PMID- 9550737
TI  - [Current developments in preventive health care].
AB  - On the occasion of the publication of the second revised edition of the
      Preventiegids (Prevention guide), some recent developments in preventive health
      care can be analysed and priorities for the near future can be formulated. Some
      controversies have been resolved (e.g. periconceptional use of folic acid,
      influenza vaccination of all elderly), a number of others still exist (e.g.
      postmenopausal oestrogen substitution, screening for hypertension and
      hypercholesterolaemia). Further health benefit can be obtained by preventive
      activities, albeit to a limited extent. The focus should be on correct
      implementation (standardisation) of existing prevention programmes plus
      evaluation, with improvements where possible. There will also be opportunities
      for new prevention programmes (e.g. use of the triple test in screening for Down
      syndrome). It will be possible to discontinue existing inefficient programmes
      (e.g. routine pregnancy ultrasonography, routine administration of iron to
      pregnant women.

PMID- 9550738
TI  - [Frequency of decisions to forgo (artificial) administration of food and fluids
      at life's end].
AB  - OBJECTIVE: To determine the frequency and characteristics of decisions to forgo
      (artificial) feeding and hydration with hastening of death as a possible result.
      DESIGN: Retrospective, descriptive study. SETTING: The Netherlands. METHODS: Data
      were collected from questionnaires mailed to physicians attending 6060 deaths
      identified from death certificates dating from August through November 1995
      (response rate: 77%). RESULTS: Decisions to forgo feeding and hydration preceded
      8% of all deaths studied; for deaths attended by nursing home physicians this
      percentage was 23%, for deaths attended by general practitioners and specialists
      it was 4%. In 68% of all these death cases, the patients had been 80 years of age
      or over, and 76% of them had been partly or completely incompetent. The non
      treatment decision had been discussed with relatives in 82% of all cases, and in
      89% of the death cases attended by nursing home physicians. These patients had
      had (possibly) life-shortening medication less frequently than other patients for
      whom a medical decision concerning the end of life had been made. CONCLUSION:
      Decisions to forgo (artificial) feeding and hydration were made relatively often
      by nursing home physicians, and rarely by general practitioners and specialists.
      These decisions were usually but not always made after discussion with relatives.
      There were no indications that these decisions entailed a great deal of suffering
      for the patients.

PMID- 9550739
TI  - [Spontaneous pneumothorax in young women: possible lymphangioleiomyomatosis].
AB  - (Recurrent) pneumothorax developed spontaneously in three women aged 33, 35 and
      36 years, two of whom were pregnant. Morbid-anatomical examination of lung biopsy
      samples in two of them revealed proliferation of smooth muscle cells which
      through infiltration of pleura, septa, and alveoli had led to loss of pulmonary
      parenchyma and formation of cystic lesions; the cystic lesions were visible in a
      CT scan in all three patients. The diagnosis in 2 patients was
      'lymphangioleiomyomatosis'; the third patient had anomalies compatible with
      lymphangioleiomyomatosis, but these were interpreted as tuberous sclerosis
      because of the presence of renal angiomyolipomas. This disorder occurs
      exclusively in women in the reproductive age. Treatment consisted in drainage of
      the pneumothorax, pleurodesis and pleurectomy, with administration of medroxy
      progesterone. One year later, the pneumothorax had not recurred.

PMID- 9550740
TI  - [HIV/AIDS in The Netherlands: improved treatment possibilities necessitate HIV
      instead of AIDS surveillance].
AB  - An abrupt decrease of the number of reported new AIDS cases took place in the
      first half of 1997 in the Netherlands. This decrease was most prominent in
      homosexual/bisexual men and intravenous drug users, and less conspicuous in
      heterosexual men and women. The number of heterosexual patients with a non-Dutch
      nationality even increased compared with the first half of 1996. The most
      probable explanation of these observations is the introduction of improved
      treatment possibilities for HIV-infected people starting July 1996, which lead to
      a longer incubation period. Owing to these developments monitoring the HIV/AIDS
      epidemic in the Netherlands will depend more and more on HIV status surveillance
      instead of on registration of new AIDS cases.

PMID- 9550741
TI  - [Deep venous thrombosis of the right leg caused by compression by an abdominal
      aortic aneurysm].

PMID- 9550742
TI  - [Adverse effects of minocycline in the treatment of acne vulgaris].

PMID- 9550743
TI  - [An innocuous prolonged unilateral nose blockage?].
AB  - A woman aged 35 and a man aged 59 had been suffering for years from unilateral
      clogged nose. Adequate diagnostic examination revealed in both of them a
      papilloma inversum from which a squamous carcinoma had developed. After extensive
      surgical resection of the tumour and irradiation, tumour progression and
      metastasization occurred. Both patients were given palliative chemotherapy; they
      died soon after the last course. Problems concerning nasal breathing are common
      in general practice. They are often attributed to common cold or to an allergy.
      Unilateral blocking of the nose is usually caused by a congenital or a traumatic
      deviation of the nasal septum. However, in adult patients, it may rarely be due
      to a tumour.

PMID- 9550744
TI  - [Immunology in medical practice. IV. Inflammatory bowel diseases: pathogenic
      starting points for specific therapy].
AB  - The cause of inflammatory bowel diseases is unknown, but T-cells play an
      important part in the pathogenesis of Crohn's disease. It was shown in recent
      years that activated T-cells produce certain cytokines that cause inflammation
      (interferon-alpha, tumour necrosis factor-alpha or TNF-alpha), but also cytokines
      (interleukin-10 or IL-10, transforming growth factor-alpha) which on the contrary
      inhibit inflammation. On the basis of this knowledge, the mucosal inflammatory
      reaction can be counteracted in a rational manner: antibodies against TNF-alpha
      in most patients with Crohn's disease who failed to respond to corticosteroids
      led to substantial reduction of disease activity. The first experiences with IL
      10 treatment of Chrohn patients are also encouraging. It is expected that in the
      near future still more forms of immunotherapy directed against cytokines will
      become available.

PMID- 9550745
TI  - [Consequences of a bipolar disorder and use of mood stabilizers for its
      management during pregnancy].
AB  - For patients with a bipolar disorder who are pregnant or consider pregnancy, the
      following issues are of importance: Genetic counselling: genetic vulnerability is
      virtually certainly the basis of the occurrence of a bipolar disorder.
      MEDICATION: discontinuation of the medication may lead to recurrence;
      continuation may cause intoxications in the woman and her child and congenital
      anomalies in the child. Alternatives to mood stabilizers can be applied;
      electroconvulsive therapy is a possibility as is medication with antidepressants,
      antipsychotics and benzodiazepines during acute episodes of mood disorder.
      Precautions for mother and child if mood-stabilizing treatment is continued: use
      sustained-release preparations, regularly check blood levels and thyroid
      function, administer vitamin K if necessary, perform ultrasonoscopy/examination
      of amniotic fluid, have the child delivered in hospital. Management of the
      newborn child: observation, determination of blood levels, regular checks of
      thyroid function, if necessary administration of vitamin K.

PMID- 9550746
TI  - [The use of drugs to improve athletic performance].
AB  - In sports, medical drugs are applied for supposedly ergogenic effects. Forbidden
      drug use (doping) implies that the drug enhances performance, which is not always
      the case. Amphetamines are ergogenic particularly during short-term, explosive
      exercise. Amphetamines exert an ergolytic effect on high-intensity endurance
      exercise. Caffeine has an ergogenic effect on endurance performance in dosages of
      3 to 6 mg/kg. Doping regulations allow a small amount of caffeine intake.
      Androgenic and anabolic steroids elicit an increase in muscle growth and
      strength. In females low doses appear to be ergogenic in all sport types. beta 2
      adrenergic agonists appear to have a positive effect on strength and muscle
      growth. The effects on endurance performance are still unknown. Although growth
      hormone is used in sports, scientific studies show that compared with placebo no
      difference in strength and muscle volume is observed. Blood doping and
      administration of erythropoietin are effective in enhancing endurance
      performance.

PMID- 9550747
TI  - [Left ventricular hypertrophy; differences in the diagnostic and prognostic value
      of electrocardiography and echocardiography].
AB  - OBJECTIVE: To compare the electrocardiogram (ECG) and the echocardiogram for
      demonstration of left ventricular hypertrophy (LVH) and the prognostic values of
      these methods. DESIGN: Literature study. SETTING: Department of General Practice,
      Social and Nursing Home Medicine, R.C. University of Nijmegen, the Netherlands.
      METHOD: Using articles retrieved by means of a search action in Medline (1962
      January 1996), a study was made of the differences between determination of LVH
      by ECG and by echocardiography with regard to the sensitivities and specificities
      for measuring anatomical LVH, and their predictive values concerning
      cardiovascular morbidity and mortality. RESULTS: The sensitivity of
      echocardiography for the prediction of anatomical LVH (88-93%) exceeded that of
      ECG (21-54%), while both methods had a high specificity (77-97%). ECG-LVH seemed
      a better predictor of cardiovascular complications than echo-LVH. CONCLUSION:
      Echocardiography is the better instrument for screening for LVH, but ECG should
      keep its place in the diagnostics of LVH in view of its high predictive value for
      morbidity and mortality and its availability to primary health care. In regard to
      LVH, echocardiography measures only morphological disorders, while ECG also
      detects functional disorders.

PMID- 9550748
TI  - [Hemophagocytic syndrome].
AB  - A lymph node biopsy sample from a boy aged with fever, pneumonia,
      hepatosplenomegaly, lymphadenopathy and pancytopenia, showed histiocytosis with
      erythrophagocytosis, compatible with the haemophagocytic syndrome. Treatment
      consisted of dexamethasone and etoposide, with cyclosporine added in a later
      phase. During the subsequent remission phase, bone marrow transplantation was
      carried out. Haemophagocytic syndrome is a rare condition, characterized by
      fever, pancytopenia, hepatosplenomegaly and characteristic laboratory findings
      (including a high interferon-gamma level) and morbid-anatomical findings
      (haemophagocytic histiocytic cells in bone marrow, lymph nodes, liver and spleen,
      but also in the CNS, kidneys and lungs). Recent pathophysiological discoveries
      indicate an enhanced T-cell response, leading to hypercytokinaemia. As a rule the
      patient dies from multiorgan failure and diffuse intravascular coagulation. Bone
      marrow transplantation is the treatment of choice.

PMID- 9550749
TI  - [Excessive terfenadine level due to drinking grapefruit juice].
AB  - Doctors who prescribe drugs should be aware not only of potential drug-drug
      interactions, but also of potential food-drug interactions. In particular, the
      ingestion of grapefruit juice leads to enhanced systemic bioavailability of
      terfenadine and of several important and frequently prescribed other drugs.
      Components of grapefruit juice interfere with the function of intestinal
      cytochrome P450 3A4, which degrades terfenadine. The resulting enhanced blood
      levels of terfenadine may lead to heart rate disturbances. Selling the drugs
      involved over the counter is consequently risky.

PMID- 9550750
TI  - [Cystic fibrosis: special value of treatment at a center].
AB  - A woman aged 30 and a man aged 40, both with a bad general condition due to
      cystic fibrosis, showed a clear clinical improvement after they were treated in a
      cystic fibrosis centre, while in a young adult male patient the diagnosis of
      cystic fibrosis could be rejected. In the Netherlands there are approximately
      1000 patients with cystic fibrosis. As a consequence most doctors have hardly any
      experience of the treatment of such patients. To optimize the treatment of
      patients with cystic fibrosis, it would seem wise to concentrate experience and
      knowledge in several cystic fibrosis centres.

PMID- 9550751
TI  - [Eye-preserving treatment of uveal melanoma. Leidse Oogmelanoom Groep].
AB  - Over 100 new cases of uveal melanoma are diagnosed annually in the Netherlands.
      In the absence of metastases, eye-preserving treatment is possible in principle.
      Since 1984, Dutch patients are referred for eye-preserving treatment to Leiden
      University Hospital which consequently has gained great experience. Brachytherapy
      (with Ruthenium-106 applicators) is only suitable for uveal melanomas with a
      diameter < or = 15 mm and a prominence (thickness perpendicular to the sclera) <
      or = 5 mm; after 10 years, the eye was preserved in 80% of the patients; 75%
      retained a visual acuity > or = 0.25. Proton irradiation is being applied for
      large, strongly prominent melanomas in patients for whom enucleation is not
      acceptable, for instance with a melanoma in the only eye still functioning. The
      eyes could be preserved in 83.3% over a period of 5 years. Transpupillary
      thermotherapy combined with episcleral Ruthenium-106 application is called
      sandwich therapy; in a study involving 50 patients, 49 melanomas (98%) began to
      regress within 4 weeks and after a follow-up period of 12 months all tumours with
      a prominence < 5 mm had regressed completely.

PMID- 9550752
TI  - [Dysplastic nevi and the risk of melanoma: a guideline for patient care.
      Nederlandse Melanoom Werkgroep van de Vereniging voor Integrale Kankercentra].
AB  - Consensus was recently reached in the Netherlands regarding the clinical
      management of dysplastic naevi and the definitions in clinical and pathological
      diagnostics. The term 'dysplastic' is reserved for histological diagnostics; the
      term preferred for clinical use is 'clinically atypical naevus'. A naevus is
      defined as clinically atypical if it meets three of the following five criteria:
      > or = 5 mm in diameter, vaguely bordered, asymmetrically shaped, irregularly
      pigmented and a red hue (erythema). Presence of clinically atypical naevi is a
      main risk factor for melanoma. Dysplastic naevus syndrome (DNS) is present if a
      patient has a melanoma and one or several clinically atypical naevi. The
      diagnosis of 'familial DNS' (familial atypical multiple mole-melanoma syndrome,
      abbreviation FAMMM syndrome) is made if at least two close relatives (including
      the patient) are known with a melanoma with or without atypical naevi, while one
      or several (other) relatives have atypical naevi. The risk of melanoma in a gene
      carrier of familial DNS is close to 100%, while multiple melanomas develop in 30%
      of the gene carriers. No DNA diagnostics is yet possible in most DNS/FAMMM
      families, because of the involvement of genes yet unknown. Accordingly, at
      present it is still too early for DNA diagnostics. Currently, therefore, the
      diagnosis is based only on anamnestic, clinical and histological grounds.

PMID- 9550753
TI  - [2nd revised consensus skin melanoma. De Nederlandse Melanoom Werkgroep].
AB  - The 'Guideline melanoma of the skin, second revised consensus' was published in
      March 1997. Some of the contents are cited: Over 1600 new melanomas are diagnosed
      in the Netherlands each year; by now the mean 5-year survival amounts to over
      80%. In examination of a pigmented lesion a dermatoscope is a valuable tool. The
      recommended margin of the diagnostic excision was reduced from 5 mm to 2 mm of
      macroscopically normal skin round the lesion; the margins in definite excision
      are: 1 cm of normal skin for a Breslow thickness < or = 2 mm; 2 cm for a Breslow
      thickness > 2 and < or = 4 mm. A margin of at least 2 cm seems also justified for
      thicker melanomas. Elective (prophylactic) regional lymph node dissection is
      advised against. Sentinel node biopsy appears to be an attractive method to
      detect occult metastasis in regional nodes. In lymph node metastasis a
      (therapeutic) regional lymph node dissection should be performed. In case of
      inoperable tumourgrowth in an extremity regional isolated perfusion is indicated.
      Radiotherapy may be applied curatively (e.g. if surgery is not possible),
      palliatively (if desired in combination with hyperthermia) or postoperatively (if
      non-radical resection is suspected). Adjuvant systemic therapy in melanoma
      patients is still experimental; the earliest results of high doses of interferon
      alpha are encouraging. Atypical (dysplastic) naevi and congenital naevi are
      important risk factors for melanoma. No consensus was reached regarding
      prophylactic removal of all congenital naevi. Regarding the duration of the
      follow-up period, 5 years suffices in patients with a melanoma with a Breslow
      thickness < or = 1.5 mm (provided there are no histological signs of regression),
      while 10 years is required for melanomas with a Breslow thickness > 1.5 mm. The
      patient should be actively involved in the follow-up (inspection, palpation).
      Routine blood testing, roentgen examination or ultrasonography are considered to
      be useless. There are no indications that hormonal alterations during pregnancy
      or use of the pill stimulate the growth of micrometastases that may be present.
      Excessive exposure to ultraviolet rays is discouraged.

PMID- 9550754
TI  - [The white coat in pediatrics: link between medical history and preference for
      informally dressed physicians].
AB  - OBJECTIVE: To find out if children show a preference for a doctor in a white coat
      or an informally dressed doctor, and what factors influence this preference.
      Further to determine if children show a preference for a physician of their own
      or of the other sex. METHOD: A series of 20 pairs of photographs showing varying
      combinations of a male and a female doctor in a white coat or in informal dress
      was presented to test subjects: 37 children without a medical history, 28
      children with a minor and 16 with an extensive medical history, aged between 6
      and 12 years. Out of each pair of photographs, the test subjects were invited to
      choose the doctor they would prefer. RESULTS: On average, the test subjects opted
      for a doctor in a white coat more often than for an informally dressed doctor (p
      < 0.05). There was a significant difference in dress preference between children
      with a less and with a more extensive medical history (p = 0.001): children with
      no medical history more often chose a doctor in a white coat. Children with an
      extensive medical history more frequently showed preference for informal dress.
      The children opted more frequently for a doctor of their own sex (p < 0.001).
      CONCLUSION: The preference of children for a doctor in a white coat or for an
      informally dressed doctor depended on their medical history. The more extensive
      the medical history, the more the preference shifted to an informally dressed
      doctor. Also, the children preferred a doctor of their own sex.

PMID- 9550755
TI  - [Prader-Willi syndrome in a young infant].
AB  - Four children aged 2.5 years, 15.7 and 7 months, including a pair of twins, after
      birth displayed hypotonia which necessitated tube feeding. Other features were a
      narrow forehead and a thin triangular upper lip, but these abnormalities were not
      conspicuous. An extensive supplementary examination for cerebral and muscular
      disorders initially failed to produce a diagnosis. It was only when the Prader
      Willi syndrome was suspected and a corresponding abnormality on chromosome 15 was
      looked for that this diagnosis could be made. Early diagnosis of this syndrome
      will avoid further invasive diagnostic procedures and make early treatment
      possible.

PMID- 9550756
TI  - [Arthritis caused by use of rifabutine++ in Mycobacterium avium infection].
AB  - A 60-year-old HIV-seronegative man with a Mycobacterium avium pulmonary infection
      was treated with rifabutin, ethambutol and clarithromycin. He developed a serious
      arthritis which disappeared after interruption of the medication and recurred
      after resumption. The arthritis was attributed to the use of rifabutin. This
      adverse effect is more frequent with higher doses and in combination with the use
      of macrolide antibiotics.

PMID- 9550757
TI  - [Zidovudine-resistant HIV strains in untreated intravenous drug users and
      homosexual men in Amsterdam infected in 1996].
AB  - OBJECTIVE: To gain insight into the spread of HIV strains with different
      sensitivities to antiretroviral drugs prescribed in the Netherlands. DESIGN:
      Prospective cohort study in intravenous drug users and homosexual men. SETTING:
      Amsterdam, the Netherlands. METHODS: HIV negative participants in the Amsterdam
      cohort studies among homosexual men and intravenous drug users are tested two to
      three times a year for HIV antibodies. The first positive serum sample of those
      who seroconverted was used to determine, on the basis of the nucleotide sequence
      of the reverse transcriptase gene of HIV, if viruses were present with a reduced
      sensitivity to reverse transcriptase inhibitors. RESULTS: In 1996, 17 new HIV
      infections occurred (8 in homosexual men and 9 in intravenous drug users). In two
      new infections in homosexual men HIV strains with reduced sensitivity to
      zidovudine were present.

PMID- 9550758
TI  - [More rapid recovery and fewer recurrences following laparoscopic inguinal hernia
      surgery than after conventional surgery; a prospective, randomized study].

PMID- 9550759
TI  - [More rapid recovery and fewer recurrences following laparoscopic inguinal hernia
      surgery than after conventional surgery; a prospective randomized study].

PMID- 9550761
TI  - [Scratching for the itch in eczema; a psychodermatologic approach].
AB  - Atopic dermatitis patients often complain of intense itching and excessive
      scratching. Apart from standard therapies of antihistamines with sedative side
      effects, there are patients who appear not to respond satisfactorily to standard
      medical treatments. As itching can be a skin manifestation of psychological
      disturbance, these patients may benefit from behaviour treatment of scratch
      behaviour which can have a beneficial effect on the course of atopic eczema. The
      scratch response is considered a classical conditioned habit and special
      attention was given to the function of behaviour. Two patients, a man of 27 and a
      girl of 11, were suffering from intractable atopic eczema. The first patient was
      required to record his own scratching in a diary which is part of awareness
      training regarding scratch situations. In the second patient impaired parent
      child relationships were the main discriminative stimuli to provoke scratch
      behaviour. It was shown that behaviour therapy helps patients who scratch
      repeatedly to exercise voluntary control over it.

PMID- 9550762
TI  - [Dutch drug registration: greater openness is urgently desired].
AB  - The centralized European registration of drugs is characterized by relative
      openness, like the publication of public assessment reports. In our country the
      registration authorities should also be more focused on the users and become more
      accountable for their decisions. Then, in their daily practice, the prescriber
      and pharmacist can make better use of the available expertise.

PMID- 9550763
TI  - [Immunology in medical practice. V. Constitutional eczema].
AB  - Constitutional eczema (late atopic dermatitis) is a frequent condition: some 30%
      of the skin diseases seen by the GP involve constitutional eczema. A number of
      links with (external) factors have meanwhile been established. Patients with
      constitutional eczema often suffer from food allergy (over 60% of the children
      with the eczema) and many are allergic to airborne allergens (especially
      housedust mite allergen). The skin of patients with constitutional eczema has a
      diminished barrier function against irritants (soaps, acids, bases, water,
      detergents, biological juices (fruit, meat, fish, vegetables). In 90% of the
      patients with constitutional eczema the skin contains colonies of Staphylococcus
      aureus (in 5% of people without eczema). S. aureus can influence the eczema
      through exoantigens (so-called superantigens) and through conventional antigens
      that may evoke an IgE-mediated immune response. Emotional stress may influence
      the eczema. The close anatomical relationship between mast cells and nerve
      endings and between Langerhans cells and nerve endings suggest that the
      autonomous nervous system can modulate the immune system of the skin and
      consequently, the eczema. These factors should be taken into account in the
      treatment: reduction of exposure to food and airborne allergens and to irritants,
      treatment and prevention of S. aureus infections and psychological support. New
      therapies include cyclosporine, autologous IgG antigen complexes and
      phototherapy.

PMID- 9550764
TI  - [High-dose chemotherapy followed by hematopoietic stem cell transplantation as
      therapy for systemic rheumatic autoimmune diseases].
AB  - Remissions of autoimmune diseases can be accomplished in animals by myeloablative
      chemotherapy followed by allogeneic or autologous bone marrow transplantation.
      Remissions of autoimmune diseases have been reported in patients with concomitant
      malignancies for which they were treated with myeloablative chemotherapy followed
      by stem cell transplantation. Survival of patients with systemic rheumatic
      autoimmune disease is reduced. Since transplantation related mortality after
      autologous stem cell transplantation is less than 5%, this treatment becomes a
      possibility for patients with severe systemic rheumatic autoimmune disease, such
      as systemic sclerosis.

PMID- 9550765
TI  - [Usefulness of the 'Mini-Mental State Test'for the diagnosis of dementia; study
      of criterion validity in a Dutch rural population].
AB  - OBJECTIVE: To establish the criterion validity of the MMSE for dementia in a
      community-based population. DESIGN: Descriptive. SETTING: Eight rural general
      practices and eight adherent institutions for long-term care near Zwolle, the
      Netherlands. METHODS: In the first (screening) stage, the MMSE was applied, in
      the second (diagnostic) stage the 'Cambridge examination for mental disorders of
      the elderly' (CAMDEX) was used. After exclusion of subjects with clinically
      relevant impairment of hearing and (or) vision, analyses were based on 2151
      screened subjects. Based on a non-proportional, stratified randomized sampling
      procedure using the MMSE score as the stratification variable, 390 of the
      screened subjects were examined with the CAMDEX. Seventy-seven cases of DSM-III-R
      dementia were identified. Based on 390 paired observations the relationship
      between MMSE score and DSM-III-R dementia was modelled by logistic regression.
      After extrapolation of this relationship to the total screened population,
      sensitivity and specificity figures were calculated at several cut-offs of the
      MMSE, and Receiver Operating Characteristic (ROC) curves were constructed for the
      total population as well as for four subpopulations. (men, women, < 80, > or = 80
      years). RESULTS: At the cut-off of 23/24, sensitivity was 0.76 and specificity
      0.91 in the total population. However, the criterion validity of the MMSE varied
      substantially between the four sex-age combinations. Criterion validity was
      especially poor for women in the younger age range. CONCLUSION: The MMSE has only
      limited value in clinical practice. Use of uniform cut-offs has to be rejected.

PMID- 9550766
TI  - [Inguinal hernia in a young girl; sporadic manifestation of testicular
      feminization].
AB  - Examination of a woman aged 17 years with primary amenorrhoea revealed normal
      breasts and external genital organs, hardly any axillary or pubic hair growth, a
      blind vaginal pouch and no palpable uterus or adnexa. At additional examination,
      uterus and adnexa proved to be absent, the serum testosterone concentration was
      substantially increased and the karyotype was 46,XY. The diagnosis was
      'testicular feminization' (androgen insensitivity syndrome). The patient in
      childhood had undergone a bilateral inguinal hernia operation, at which 'ovaries'
      were found in the hernial sacs. It might have been interpreted as the first sign
      of the syndrome; such a finding necessitates further examination. Most patients
      with testicular feminization seek medical advice because of primary amenorrhoea.
      Early diagnosis is important because the risk of malignant degeneration of the
      intra-abdominal testes increases with advancing age (sometimes also in
      relatives). Also it makes it possible gradually to prepare the child for her
      future.

PMID- 9550767
TI  - [Endometriosis in the round ligament of the uterus as a cause of inguinal pain].
AB  - Within one year three patients, women aged 31, 28 and 26 years, presented with a
      cyclic painful small mass in the inguinal region. Histopathological examination
      of the resected specimen showed a pattern consistent with an extra-abdominal
      localization of endometriosis in the round ligament. The patients' complaints
      disappeared after surgical resection. It is concluded that in case of a painful
      mass in the inguinal region in a fertile woman endometriosis of the round
      ligament should be considered.

PMID- 9550768
TI  - [Acute perceptive hearing loss and metabolic acidosis as complications of the
      topical treatment of psoriasis with salicylic acid-containing ointment].
AB  - A 36-year-old woman, hospitalized because of an exacerbation of psoriasis,
      developed fever, sudden deafness and severe metabolic acidosis after treatment
      with a 10% salicylic acid containing ointment for four days. The use of salicylic
      acid on large areas of inflamed skin enhances the risk of transcutaneous
      resorption and intoxication. High serum concentrations (> 300 mg/l) of salicylic
      acid deregulate the blood glucose metabolism and cause damage to the inner ear.
      After timely intervention such symptoms are largely reversible.

PMID- 9550769
TI  - [Stimulation Program Health Research. XI. Evaluation of the section
      'Rehabilitation Medicine'].
AB  - As a part of the SGO Health Research Promotion Programme a research programme on
      rehabilitation medicine was realized. Aim of the programme was to strengthen
      clinical research in this field by training clinical researchers and improving
      clinical research infrastructure. Three clinical specialists have been trained to
      become senior clinical researchers by a 4-year training programme, concentrated
      within 2 clusters of a medical faculty, a university hospital and one or more
      centres for rehabilitation medicine. As a follow-up to the programme a 6-week
      educational course was developed for intending MDs in rehabilitation medicine and
      five intending rehabilitation medicine specialists receive a PhD research
      training during their clinical specialisation.

PMID- 9550770
TI  - [Pain control in the terminal stage of life].
AB  - A 67-year-old woman suffered from terminal cancer as a consequence of local
      recurrence of endometrial carcinoma which had been treated by hysterectomy. She
      had excruciating pains and was requesting euthanasia. Advanced techniques for
      pain relief e.g. intrathecal administration and nerve blocks resulted in adequate
      relief and postponed the request. Besides knowledge and skill, the application of
      these techniques requires a logistic network in the home situation. An
      alternative therapeutic approach for this patient would have been continuous
      intravenous administration of morphine, which would have implied accepting an
      earlier death. The Dutch National Inquiry on euthanasia and life ending
      interventions revealed that in 19.1 per cent of the overall mortality in the
      Netherlands, pain treatment had contributed to death. In 1.4 per cent (1900 cases
      per year) death was even the main goal of pain treatment. A wider application of
      advanced pain relieving techniques can diminish requests for euthanasia in the
      Netherlands and also can curtail mismanagement of pain. An advice from 1991 of
      the National Health Council for better hospital support for terminal patients in
      the home situation is still awaiting implementation.

PMID- 9550771
TI  - [Vulvodynia caused by vulvar vestibulitis syndrome].
AB  - Vulvodynia is a puzzling disorder. Patients experience clear physical complaints
      of vulvar burning. Often they have consulted many physicians and tried all kinds
      of treatment. Vulvodynia is often caused by the vulvar vestibulitis syndrome
      (VVS). To detect VVS an extensive medical and psychosexual history is necessary.
      Thorough examination of the vaginal vestibule reveals the typical focal
      erythematous lesions. The aetiology of VVS is unknown. Of the many causal and
      perpetuating factors a sexual arousal disorder and pelvic floor hypertonia are
      the main ones. The psychodynamic aspects of these two core symptoms are principal
      issues in diagnosis and treatment of VVS. Treatment should include all physical,
      psychological, relational and sexual aspects of the problem. Surgical
      interventions should be limited to those rare cases in which an integrative
      approach fails to free the patient from the vicious circle of pain, anxiety and
      muscle tension.

PMID- 9550772
TI  - [Effect of protein restriction on deterioration of kidney function].
AB  - The results of meta-analyses and of the recent 'modification of diet in renal
      disease' study show that dietary protein restriction slows down deterioration of
      renal function in patients with a moderately impaired renal function. However,
      this effect appears to be less pronounced than previously assumed. Protein
      restriction probably leads to narrowing of the preglomerular blood vessel, which
      reduces the raised intraglomerular pressure. The resulting decrease in the
      filtering glomerular pressure initially leads to a slight loss of renal function,
      but there after to a decelerated deterioration of renal function. The aim should
      be a protein intake of 0.6-0.75 g per kg per day. Dietary compliance should not
      be predicted anamnestically but should be calculated according to the (modified)
      Maroni equation (protein intake = (0.18 x urinary urea excretion in mmol per 24
      hours) + 15 + urinary protein excretion in g per 24 hours). This kind of protein
      restriction as a rule does not lead to nutritional deficiencies.

PMID- 9550773
TI  - [Multidisciplinary treatment of cerebral arteriovenous malformations: preliminary
      results in 115 consecutive patients].
AB  - OBJECTIVE: Preliminary evaluation of the combined treatment (surgery,
      embolization and stereotactic gamma radiosurgery) of 115 consecutive patients
      with a cerebral arteriovenous malformation (AVM). DESIGN: Retrospective. SETTING:
      St. Elisabeth Hospital, Tilburg, the Netherlands. PATIENTS AND METHODS: In a 35
      month period 115 consecutive patients presented with an AVM. The mean age was
      41.8 years (range: 6-72). The main clinical presentation was haemorrhage in 65
      patients (56.5%), seizures in 31 patients (27.0%), neurological deficit in 7
      patients (6.1%) and hydrocephalus in 2 patients (1.7%); in 10 patients (8.7%) the
      AVM was an incidental finding. Treatment consisted of surgery, radiosurgery with
      the gamma knife and embolization. Embolization was mostly used to reduce the size
      of an AVM before surgery or radiosurgery. RESULTS: Out of 115 patients 5 were
      referred for a treatment advice only and treatment was performed elsewhere. Of
      the remaining 110 patients 84 (76.4%) were treated and 26 (23.6%) were not
      treated for various reasons. Of the 84 treated patients 17 (20.2%) had surgery
      only, 17 (20.2%) had radiosurgery only, and 12 (14.3%) were treated with
      embolization only. Surgery after embolization was performed in 8 patients (9.5%)
      and radiosurgery after embolization in 26 patients (31.0%). In 4 patients an
      unusual combination of these treatment methods was used for a variety of reasons.
      At the time of writing 35 of 84 treated AVMs (41.7%) were completely cured, 39
      patients were awaiting the definitive result of radiosurgery. Deliberate partial
      embolization was performed in 5 patients. In 5 patients (6.0%), the pretreatment
      objective was not achieved with embolization. Total permanent morbidity was 4.8%
      (4 patients) and mortality was 1.2% (1 patient). CONCLUSIONS: Given a
      multidisciplinary combination of treatment methods a treatment is indicated and
      possible in the majority (76.4%) of patients with an AVM. There is a reasonable
      chance of a complete cure with an acceptable complication rate.

PMID- 9550775
TI  - [Invagination in adults].
AB  - Two adult patients with intussusception were both diagnosed by colonoscopic
      investigation. The first patient, a woman aged 39, suffered from persisting
      abdominal discomfort with nausea and vomiting. Ultimately an ileo-ileocolic
      intussusception caused by an inflammatory fibroid polyp of the ileum was found.
      The other patient, a man of 79 years, complained of subacute cramping pain in the
      right lower abdomen. This was due to an ileocolic intussusception caused by an
      adenocarcinoma of the cecum. Both patients underwent an ileocecal resection;
      their postoperative courses were uneventful.

PMID- 9550776
TI  - [Sodium polystyrene sulfonate (Resonium A) as possible cause of rectal blood
      loss].
AB  - A 67-year-old man underwent laparotomy for a ruptured aneurysm of the abdominal
      aorta. Postoperatively he was treated with haemodialysis because of
      perioperatively developed acute renal failure. Hyperkalaemia was temporarily
      treated with sodium polystyrene sulfonate (Resonium A) after which he lost blood
      per rectum. A hemicolectomy was necessary because of intractable blood loss due
      to ulceration of the colon. This complication is related to uraemia and the use
      of sodium polystyrene sulfonate with or without sorbitol.

PMID- 9550777
TI  - [Antithrombotic treatment following acute ischemic heart disease: acetylsalicylic
      acid and (or) oral anticoagulants?; ASPECT-II, a new study].
AB  - In order to compare the efficacy and safety of three regimens of long-term
      antithrombotic treatment in patients with acute ischaemic syndromes, a
      prospective, randomized, open-label, multicentre study is being conducted in
      which 60-70 Dutch hospitals will participate. Eligible patients discharged
      following hospitalization for acute myocardial infarction or unstable angina
      pectoris are randomly assigned to receive either (a) adjusted full intensity oral
      anticoagulation (target range: 3.0-4.0 International Normalised Ratio (INR), (b)
      low dose aspirin or (c) combined therapy of low dose aspirin and adjusted low
      intensity oral anticoagulation (target range INR: 2.0-2.5). It is planned to
      enroll 8,700 patients within three years. During an estimated mean follow-up of
      2.5 years the evolutions of total mortality, non-fatal myocardial infarction, non
      fatal stroke and major bleeding complication will be assessed.

PMID- 9550778
TI  - [Appeal for the reporting of unpublished clinical research].

PMID- 9550779
TI  - [At which childbirth should endocarditis prophylaxis be given?].

PMID- 9550780
TI  - [The maxillary sinus and odontogenic cysts].
AB  - An unilateral maxillary sinusitis is frequently caused by dental pathology. An
      odontogenic cyst in the maxillary sinus usually lacks accompanying symptoms of
      infection. In three patients, a 35-year-old man and two women aged 16 and 28, an
      odontogenic cyst in the maxillary sinus was diagnosed. Consultation of a
      maxillofacial surgeon is needed because orthopantomographic imaging is
      diagnostically most helpful. In these patients combined treatment by an ENT
      surgeon and a maxillofacial surgeon is important.

PMID- 9550781
TI  - [Indications for influenza vaccination in children with lung disorders. Dutch
      Association for Pediatric Medicine].
AB  - The Dutch Association for Paediatric Medicine has formulated guidelines regarding
      influenza vaccination of children with pulmonary disease. Influenza virus is the
      most frequent cause of airway infections in humans over two years of age. It may
      lead to serious morbidity in children with pulmonary disease: exacerbations,
      (transient) disturbances in pulmonary function, and symptoms lasting weeks, but
      mortality is probably very low. The effects of influenza vaccination of children
      with pulmonary disease are similar to those in normal healthy children. A
      positive long-term effect on the asthma has never been demonstrated. It is
      advised that children with moderate to severe asthma who require treatment to be
      vaccinated against influenza every year. If the first vaccination ever occurs
      before the age of six years, it should be followed by a booster vaccination after
      four weeks. In both instances, a full vaccination dose should be administered.

PMID- 9550782
TI  - [Bisphosphonates in the treatment and prevention of bone metastases].
AB  - Bone metastases occur frequently in cancer and are commonly associated with bone
      degradation due to the tumoral production of factors which stimulate the
      development and activation of osteoclasts. During osteolysis growth factors are
      released which stimulate tumour growth. Bisphosphonates inhibit osteoclastic bone
      resorption. Recently, in several large randomised studies of patients with
      multiple myeloma or bone metastases of breast cancer, long-term treatment with
      clodronate or pamidronate gave significant bone protection.

PMID- 9550783
TI  - [Treatment of asthma in children; revised guidelines by pediatric pneumologists.
      Section of Pediatric Lung Diseases of the Dutch Association of Pediatric
      Medicine].
AB  - The diagnosis of 'asthma' is still based on anamnesis, physical examination and
      lung function tests. Supplementary examinations (laboratory or roentgen) are
      carried out only if indicated. Most young children with recurrent periods of
      wheezing and coughing prove not to develop asthma in the long run. Oral
      medication no longer has a place in the treatment of asthma, since inhalation
      medication is now possible at all ages, among other things because of the current
      availability of new nozzle attachments. Every child with asthma should have a
      short-acting beta 2-agonist at hand. Furthermore, inhaled corticosteroids are the
      maintenance drug of choice in children with moderate or severe asthma. Systemic
      effects may occur with every inhaled corticosteroid, even with dosages usual for
      children, but these are rarely relevant. Cromones nowadays play a very limited
      part. Long-acting beta 2-agonists are indicated in children whose asthma cannot
      be controlled with standard doses of inhaled corticosteroids. In the prevention
      of allergic asthma of childhood, prescription of the allergen-tight mattress
      cover plays a main part. The physician has an important task in discouraging
      (passive) smoking. Young children who, in spite of treatment with inhaled
      corticosteroids, have recurrent episodes of wheezing and coughing. and children
      requiring high doses of inhaled corticosteroids (over 400 micrograms
      beclomethasone/budesonide or 250 micrograms fluticasone) should be referred to a
      paediatrician. The asthma nurse has an important task in instructing and advising
      the asthmatic child and its parents. Self-management programmes may be of great
      psychological value for the patient and his environment.

PMID- 9550784
TI  - [Lung transplantation in children].
AB  - The first lung transplantation in the Netherlands was carried out in 1990. Since,
      the operation has been performed in over one hundred adults and two children (up
      to 16 years) with chronic respiratory insufficiency. Most lung transplantations
      in children are performed because of cystic fibrosis. After referral, the patient
      is given information about the operation and the pre- and postoperative periods,
      and the transplantation team advises on the time of screening. Some one-third of
      the children referred ultimately undergo transplantation; the others refrain from
      the operation, are rejected or die during the waiting period. Owing to a shortage
      of donor lungs the waiting period for transplantation may last over one year. A
      possible but controversial solution is donation of a pulmonary lobe by a close
      relative. Undergoing lung transplantation places a heavy (psychic) burden on the
      patient and his parents. Every patient after lung transplantation goes through an
      average of two or three periods of acute rejection. Chronic rejection occurs in
      20-40%. Other complications are connected to medication (infections, renal
      dysfunction) or to the underlying disease (diabetes mellitus in cystic fibrosis).
      The percentages of survival for 1, 2 and 4 years are approx. 60-70, 55-60 and 30
      50, dependent in part on the type of lung transplantation (unilateral, bilateral
      or combined heart-lung transplantation). A reasonable condition of the patient
      owing to timely referral is a positive prognostic factor.

PMID- 9550785
TI  - [Clinical judgment and decision making in medical practice. A patient with
      shoulder symptoms].
AB  - A 49-year-old man consulted his general practitioner because of left shoulder
      pain. Analgesics brought no relief. He had a numb feeling in the left axilla.
      Cervical MRI revealed a herniated disc Cv-Cvi, for which the patient was treated
      surgically. However, the pain persisted. In retrospect, the axillary numbness
      could not have been caused by a Cv-Cvi problem, because C6 does not innervate the
      axilla. Repeated MRI, now of the cervicothoracic region, revealed a tumourous
      process around TI-TII. Thoracotomy was performed and a mesothelioma was found.
      The patient died shortly afterwards. It is stressed that the diagnostic
      satisfaction of a positive MRI finding should not lead to disregarding
      discrepancies between these radiological results and the clinical findings.

PMID- 9550786
TI  - [Epidemiology of prenatal diagnosis and selective pregnancy termination because
      of fetal neural tube defects in The Netherlands in comparison to other European
      countries].
AB  - OBJECTIVE: To describe the epidemiological impact of prenatal diagnosis and
      selective abortion on the frequency of neural tube defects (NTD) in the period
      1980-1992 in the Northern Netherlands in comparison with data from other European
      regions. DESIGN: Descriptive. SETTING: 17 'European registration of congenital
      anomalies' (EUROCAT) registrations, localized in 10 European countries. METHOD:
      Data were collected actively and retrospectively from multiple sources fed by
      voluntary registration of congenital anomalies in live births, stillbirths and
      pregnancies terminated because of congenital anomalies. RESULTS: In Europe the
      total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000
      in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In
      live births the difference was ninefold: ranging from 2.0 per 10,000 in Paris to
      18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence
      among live births, higher than in other regions in continental Europe. For spina
      bifida the live birth prevalence both in other continental regions and in Glasgow
      was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein
      screening apparently led to frequent early prenatal diagnosis of NTD and to
      frequent termination of pregnancy. In Paris the use of ultrasound screening
      appears to lead to frequent later prenatal diagnosis, as well as frequent
      termination of pregnancy. CONCLUSION: In the Netherlands the impact of prenatal
      diagnosis and selective abortion is limited, so that primary prevention
      (periconceptional use of folic acid) is more important than in some other
      European countries.

PMID- 9550787
TI  - [Heart tamponade: a life-threatening complication of a central venous catheter].
AB  - A 57-year-old female patient initially admitted with acute pancreatitis became
      extremely hypotensive, with increased central venous pressure, a few hours after
      insertion of a central venous catheter into the right subclavian vein.
      Echocardiography revealed a large amount of pericardial fluid, which was removed
      by pericardiocentesis. A cardiac tamponade as a result of central venous
      cannulation is a rare but serious complication with a high mortality rate. The
      tamponade may be the result of perforation of the V. cava superior, the right
      atrium or the right ventricle (as in the patient described). Cardiac tamponade
      should be suspected in any patient with severe hemodynamic problems after
      insertion of a central venous line.

PMID- 9550788
TI  - [Residents not-in-training and hospital physicians: the pariahs in the
      hospital?].
AB  - Patient care in Dutch hospitals is performed by medical specialists and residents
      in training for the various specialties. In addition there is an increasing
      number of young physicians who are not (yet) in training: this category has
      arisen because of a restriction of the number of medical specialists. Recently a
      new career has been put forward in advertisements, offering training for
      positions at a level below that of the traditional medical specialists. This
      development is worrisome in view of the quality of patient care and the
      perspectives of young doctors.

PMID- 9550789
TI  - [MRI recommended for patients with axillary lymph node metastases from an occult
      breast carcinoma].

PMID- 9550790
TI  - [Pleurodesis in malignant pleural effusion].

PMID- 9550791
TI  - [The 'medical work disability criterion'].

PMID- 9550792
TI  - [Too old for diagnosis or treatment?].
AB  - In three patients, two men aged 84 and 80, and a women aged 88, physicians had
      advised against further diagnostic examination or treatment, mainly because of
      the advanced age. One of the patients was not satisfied with his deterioration
      and asked for further examination, the other two were brought to the hospital by
      relatives in order to be further examined. In all three cases, additional
      investigation revealed treatable disorders (Crohn's disease, depressive disorder
      and complications of Parkinson's disease). It is argued that very old age as such
      is not a sufficient reason to refrain from further diagnostic investigation or
      treatment. Sufficient reasons are (a) certainty with respect to the diagnosis,
      (b) knowledge of technical aspects of diagnosis and treatment, notably regarding
      potential yield and stress for the patient, and (c) approval by the patient, his
      representative or family members.

PMID- 9550793
TI  - [Treatment of genital prolapse in very old women].
AB  - An until recently mobile woman of 86 years developed problems with independent
      living because of a genital total prolapse. After treatment by high perineoplasty
      she was once more able to resume her social activities. In very old women a
      genital prolapse can lead to significant morbidity due to hygienic problems and
      increase of social loneliness due to impairment of mobility. Use of a pessary is
      rarely an acceptable solution because of ulceration of the vaginal wall. Surgery
      can be modified because preservation of vaginal function is hardly necessary
      after the age of eighty. Efficient control of complaints can be achieved by
      Labhardt high perineoplasty or Le Fort partial colpocleisis. Before such types of
      operation cytology and ultrasonography of the uterus must be performed to exclude
      a malignancy with reasonable certainty. Both operations can be done under local
      anaesthesia with very short hospitalization.

PMID- 9550794
TI  - [Diagnosis and treatment of non-Hodgkin lymphoma in elderly patients].
AB  - Non-Hodgkin's lymphoma (NHL) is relatively frequent among elderly patients: more
      than half of the diagnoses in the Netherlands concern patients aged 65 years or
      above. The treatment depends on histological type, clinical stage and prognostic
      group. Increasingly, a treatment decision is made after determination of the
      prognostic group on the basis of the expected response and survival. In elderly
      patients intensive treatment frequently has more toxic effects. The expected gain
      in survival has to be weighed against more toxicity and loss of quality of life
      during and after the therapy. This is notably important for patients with low
      grade NHL, which requires only intermittent treatment. It is possible to cure
      some elderly patients with NHL of intermediate or high grade malignancy provided
      they are adequately treated with combination chemotherapy. Patients with low
      grade NHL or poor clinical condition may benefit temporarily from palliative
      treatment, in the planning of which quality of life has to be taken into account.

PMID- 9550795
TI  - [Treatment of elderly patients with acute myeloid leukemia].
AB  - More than 50% of patients with acute myelogenous leukaemia are 60 years or older.
      Unlike the results of treatment of younger adults, the outcome in patients of
      higher age has been disappointing because intensive chemotherapy is tolerated
      less well, complications due to cardiac and pulmonary comorbidity occur sooner,
      toxicity due to reduced hepatic and renal function occurs earlier and older
      patients often present with leukaemia that is intrinsically of higher risk (e.g.
      unfavourable cytogenetics). Remission-induction therapy with an anthracycline
      derivative and cytarabine results in complete remission rates of approximately
      50% in older patients; 15-20% of these remain free of leukaemia beyond 2-3 years
      and have a good quality of life. The clinical use of hematopoietic growth factors
      as adjuncts to chemotherapy to reduce complications and improve survival has not
      (yet) fulfilled his promise. By selecting older patients without major
      comorbidity for therapy and assessing the response to a first cycle of
      chemotherapy one may identify patients with the best response to treatment and
      avoid continued therapy in patients with poor prognosis. In this way the choice
      of treatment of the individual older patient can be optimized.

PMID- 9550796
TI  - [Infections in elderly patients].
AB  - Infections are an increasing problem in the elderly population, because of the
      often atypical presentation and the more frequent occurrence of complications,
      which lead to increased morbidity and mortality. The increased prevalence of
      infections in the elderly is due to a number of factors: increased exposure to
      micro-organisms (especially in nursing homes); degeneration of various organs
      (atherosclerosis, pulmonary emphysema, diverticulosis, prolapse); decreased
      immune response; concomitant diseases (e.g. diabetes mellitus) and (or) use of
      medication. There is often a delay in the diagnosis because the presentation of
      infection in the elderly is frequently atypical and symptoms are attributed to
      old age, rather than to infection. Treatment may be hampered by increased
      resistance of micro-organisms, interaction with other drugs and toxicity
      problems.

PMID- 9550797
TI  - [Aging and cardiology; various physiological, pathophysiological and clinical
      aspects].
AB  - The main cardiovascular effect of aging is a rise of the systolic blood pressure
      due to reduced impedance of the central arteries. The resulting increase of the
      afterload leads to hypertrophy, increased rigidity and lengthening of the
      relaxation period in the left ventricle. The manifestations of ischaemia or
      arrhythmias are often atypical at more advanced ages and may delay diagnosis.
      Ejection murmur due to stenosis of the aortic valve, to calcification or
      degeneration, may be difficult to distinguish from a functional murmur. The cause
      of heart failure is usually coronary sclerosis and, less often, hypertension or a
      valvular defect. Systolic heart failure is associated with decreased
      contractility of the left ventricle and compensatory dilation, diastolic heart
      failure with reduced filling of the ventricles. Both forms respond well to acute
      treatment with antihypertensive, diuretic and (or) vasodilator drugs; the
      treatment in isolated diastolic heart failure should also focus on lowering the
      increased blood pressure and reducing the heart rate to increase the filling
      phase.

PMID- 9550798
TI  - [Daily functioning and health care utilization among persons 85 years old and
      older].
AB  - OBJECTIVE: Description of the activities of daily living and the use of care in
      relation to several determinants in persons aged 85 years and over. DESIGN: Cross
      sectional survey. SETTING: General population from the city of Leiden, the
      Netherlands. METHOD: A representative sample from the inhabitants aged 85 years
      and over of the city of Leiden was enrolled. A physician visited 239 'oldest old'
      (response rate 83%) at their places of residence, in 1991/'92. Data were obtained
      on health (joint disorder, cardiovascular disease, diabetes mellitus, Parkinson's
      disease; disorders in cognition, eyesight, hearing; limitation of mobility), self
      care and household activities in daily living and the use of care (informal care
      by neighbours or family, (geriatric) home help, district nurse, private help).
      Statistical analysis was performed by non-parametric tests and logistic
      regression. RESULTS: Of the 'oldest old' 111 (46%) lived independently, and 67 of
      them (28% of the total group) had no professional help. Almost all 'oldest old'
      had at least one health disorder. In all, 129 women (77%) and 43 men (61%) had
      restrictions in basic and (or) instrumental activities of daily living. These
      restrictions were strongly related to disorders in cognition, vision and
      mobility, less related to chronic disease and not related to hearing disorders.
      Restrictions in the activities of daily living were also related to the living
      condition. This relation was particularly strong for women. Men living without a
      partner were more likely to be institutionalised. Among the 'oldest old' who
      lived independently, restrictions in the activities of daily living were related
      to the use of care, with the exception of privately organised care. CONCLUSION:
      One out of four persons aged 85 years and over lived without professional help.
      Marked differences between the sexes were found for the interrelation between
      activities in daily living and the use of care.

PMID- 9550799
TI  - [Subnormal vitamin B6 levels in theophylline users].
AB  - OBJECTIVE: To study the effect of theophylline use on the vitamin B-6 status.
      DESIGN: Descriptive. SETTING: Department of Geriatric Medicine of Nijmegen
      Academic Hospital and Department of Pulmonary Diseases, University of Nijmegen,
      the Netherlands. PATIENTS AND METHODS: Vitamin B-6 status was determined by
      measuring pyridoxal-5'-phosphate (PLP) in whole blood (using a high performance
      liquid chromatography method, reference values: 35-107 mumol/l) in 141 patients
      from the Geriatric department (84 non-chronic obstructive pulmonary disease
      (COPD), 40 COPD patients without theophylline and 17 COPD patients with
      theophylline) and in 25 non-geriatric COPD patients on theophylline. RESULTS: Of
      the 84 geriatric non-COPD patients (mean age: 82 years; SD: 6) 56% had a
      subnormal vitamin B-6 status, of the 40 geriatric COPD patients without
      theophylline (82 years; SD: 6) 70%, of the 17 geriatric COPD patients on
      theophylline (80 years; SD: 5) 94% and of the 25 non-geriatric COPD patients on
      theophylline (62 years; SD: 11) 96%. CONCLUSION: In patients who used
      theophylline a higher prevalence of subnormal vitamin B-6 status was found than
      in patients who did not.

PMID- 9550800
TI  - [Increased chance of dying among nursing home patients with lower body weight].
AB  - OBJECTIVE: To investigate a possible relationship between changes in weight and
      mortality among nursing home patients of 65 years and older, after adjustment for
      age, sex and main diagnosis. DESIGN: Descriptive longitudinal study. SETTING:
      Dutch nursing home in Delft, the Netherlands. METHODS: For three years after
      admission the body weight of patients newly admitted from April 1st 1987 to April
      1st 1989 was measured every three months under the same conditions. It was
      recorded if a patient died or was discharged in this three-year period. The
      effects of body weight at admission, sex, age and diagnostic category
      (psychogeriatric, neurological, orthopaedic, oncological, other) on mortality
      were analysed using the univariate Cox regression analysis. The effect of the
      time-dependent covariate body weight on mortality in the nursing home was
      analysed with a combined logistic regression analysis per 3-month interval.
      RESULTS: The mean weight of the females increased from 59.7 kg (n = 194) at the
      time of admission to 63.7 kg (n = 57) three years later and that of the males
      from 64.7 kg (n = 70) to 70.3 (n = 11) due to the low body weight of those who
      died. During the first 3 months after admission mortality was high (14%) and only
      diagnosis related. In subsequent 3-month periods there was a significant
      association between mortality and weight, weight change, age and sex: the risk of
      mortality was higher for those with a lower body weight, weight loss, higher age
      and male sex. CONCLUSION: Nursing home patients with a low body weight or loss of
      weight after the first 3 months after admission, have an increased risk of death.

PMID- 9550801
TI  - [Suppurative hidradenitis].

PMID- 9550802
TI  - [Suppurative hidradenitis].

PMID- 9550803
TI  - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia also
      applicable in The Netherlands].

PMID- 9550804
TI  - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia also
      applicable in The Netherlands].

PMID- 9550805
TI  - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia also
      applicable in The Netherlands].

PMID- 9550806
TI  - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia also
      applicable in The Netherlands].

PMID- 9550807
TI  - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia also
      applicable in The Netherlands].

PMID- 9550808
TI  - [Drug treatment of prostatic carcinoma].

PMID- 9550809
TI  - [Continuation of pregnancy in infaust fetal prognosis].
AB  - In three pregnant women, lethal anomalies of the fetus were diagnosed
      ultrasonographically in the second trimester. These women decided to continue
      their pregnancies for different reasons. One woman strongly regretted her
      decision to abort a previous pregnancy. The second hoped that the doctors were
      mistaken on the prognosis. The third woman was afraid of medical interventions.
      In case of lethal anomalies of the fetus, doctors should advise their patients to
      consider both options: termination as well as continuation of their pregnancy.
      Irrespective of the women's choice, doctors ought to be committed to support the
      pregnant women in such a troublesome situation.

PMID- 9550810
TI  - [The relationship between health gain and effort in mass screening for breast
      cancer].
AB  - Mass screening for breast cancer reduces the mortality of this disease. In the
      Netherlands, with a very high incidence of breast cancer, a well organized health
      care system and a stable economic prosperity, the decision taken to implement
      nationwide breast cancer screening for the female population aged 50-70 years
      appears well-founded. The first data indeed suggest a reduction of breast cancer
      in the coming years. The effects of screening as such will be difficult to
      evaluate since the programme leads also to optimalization of breast cancer
      treatment in general. Other factors, such as adjuvant therapy, may have a
      beneficial effect on breast cancer mortality, reducing the yield of the screening
      proper. This and the non-negligible negative aspects should not be hidden from
      the public. Continuous evaluation and quality control, not only in mammography
      techniques and reading, but also in the treatment of the detected cases, are
      essential for a successful screening programme.

PMID- 9550811
TI  - [Chronic hepatitis C in hemodialysis patients].
AB  - Hepatitis C virus (HCV) is an important cause of chronic hepatitis in dialysis
      patients. With regard to epidemiology, the time on haemodialysis, the (previous)
      use of intravenous drugs as well as the number of blood transfusions received are
      important risk factors. There are strong indications suggesting nosocomial
      transmission of HCV. Strict application of infection prevention procedures in
      haemodialysis units is mandatory to restrain spread of HCV infection. Preliminary
      results show equal efficacy of alpha-interferon in normalisation of serum
      transaminases in dialysis patients and in patients with normal kidney function.
      However, in both groups relapses occur often, despite induction of remission.
      Antiviral therapy (with interferon and ribavirin) is emerging as a valid option
      to induce HCV eradication in dialysis patients. Thereafter, transplantation may
      be considered.

PMID- 9550812
TI  - [Salt sensitive blood pressure and the renin-angiotensin system in hypertension].
AB  - The relationship between (excessive) use of sodium chloride and the blood
      pressure is still equivocal. Blood pressure responses to alterations in dietary
      salt consumption vary greatly between individuals, which has led to the concept
      of salt sensitivity. Although the mechanisms which determine the degree of salt
      sensitivity are not fully understood, the renin-angiotensin system seems to play
      a key role. A relative inability of this system to respond promptly to
      alterations in salt intake may underlie the development of salt sensitivity. By
      administering drugs which block the renin-angiotensin system to patients with
      essential hypertension, blood pressure is rendered more sensitive to the effects
      of salt restriction and (or) diuretic treatment.

PMID- 9550813
TI  - [Immunology in clinical practice. VI. Current immunosuppressive drugs].
AB  - Immunosuppressive drugs are agents capable of modulating at least one type of
      immune response in vivo at doses with tolerable side-effects. Classical
      immunosuppressive drugs include corticosteroids, azathioprine, cyclophosphamide,
      methotrexate and cyclosporine. In the past two years tacrolimus and mycophenolate
      mofetil were registered as immunosuppressive drugs. Tacrolimus interferes with
      the calcium-dependent signal transduction of T-lymphocytes. Mycophenolate mofetil
      is an inhibitor of purine synthesis by inhibition of the enzyme inosine
      monophosphate dehydrogenase. Both tacrolimus and mycophenolate mofetil have
      proven efficacy in both prevention and treatment of acute allograft rejection.
      The new drugs are stronger than the classical ones but do not cause more adverse
      reactions. The value in clinical medicine of some new, promising
      immunosuppressive drugs, i.e. sirolimus (rapamycin), mizoribine, brequinar and
      leflunomide remains to be proven.

PMID- 9550814
TI  - [HIV infection and risky sexual behavior in a new cohort of young homosexual men
      in Amsterdam, 1995-1996].
AB  - OBJECTIVE: The surveillance of HIV prevalence and incidence and of sexual risk
      behaviour among young homosexual men. DESIGN: Cohort study, cross-sectional data
      presentation. SETTING: Municipal Health Service of the City of Amsterdam, the
      Netherlands. METHODS: At entry into the study participants were questioned about
      their sexual behaviour and blood or saliva samples were collected for laboratory
      determination of antibodies against HIV, hepatitis B and syphilis. RESULTS: In
      June 1995-October 1996, 429 men with a mean age of 25 years were enrolled in the
      cohort study. Of these 22 (5%) were positive for antibodies against HIV. Based on
      the duration of homosexual activity of the participants the HIV incidence in this
      group was estimated at 1% per year. Furthermore, 10% of the participants had
      experienced hepatitis B infection and 1% had serological evidence of syphilis. Of
      those under investigation 38% had practised unprotected anogenital intercourse
      with steady or non-steady partners in the last six months. CONCLUSIONS: The data
      suggest that HIV is spreading among young homosexual men. Given the high levels
      of risk behaviour continued prevention activities in this group are necessary.

PMID- 9550815
TI  - [Favorable results with intravenous antimicrobial therapy outside the hospital].
AB  - OBJECTIVE: To determine whether intravenous home treatment with antimicrobial
      drugs of patients with an infection is feasible. DESIGN: Descriptive. SETTING:
      Academic Hospital, Leiden, the Netherlands. METHODS: In October 1992 a programme
      for intravenous home treatment of patients with infectious diseases was started.
      The programme was based on self-administration of the intravenous antibiotic
      therapy by the patient. The hospital pharmacy provided the antibiotics and
      infusion devices, an infectious diseases specialist supervised the home treatment
      and the nursing staff of the First Aid Department was available to change
      infusion cannulas. After assessment of their medical and psychosocial fitness in
      which the general practitioner was involved, thorough instruction on use of the
      infusion device and care of the infusion cannula, patients were sent home.
      RESULTS: In the period October 1992-September 1996, 162 patients (median age:
      45.0 years (range: 3-82)) were treated at home for a median period of 15 days (1
      221). Osteomyelitis, arthritis, Lyme disease, septicaemia with secondary foci,
      and herpes virus infections were the most frequent indications for home
      treatment. Penicillins and cephalosporins were given in 70% of the cases,
      teicoplanin and antiviral drugs in 12% and 14%, respectively. For intermittent
      administration bolus injection, a mechanical or elastomeric pump were used, for
      continuous infusion a syringe or cassette pump. The intention of the programme
      that the patient performed the home treatment as much as possible without extra
      professional help, was realised in 82% of the patients. In 60% of the cases the
      patients were fully self supporting, in 22% family or friends played an important
      role. CONCLUSION: Home treatment with antimicrobial drugs intravenously is quite
      feasible. If this were fully implemented, about 1400 patients in the Netherlands
      could be treated in this manner.

PMID- 9550816
TI  - [A patient with generalized actinomycosis].
AB  - A 36-year-old man was admitted because of haemoptysis and weight loss. Despite
      elaborate investigations, including multiple biopsies of affected organs (pleura,
      lung, kidney and liver) no diagnosis was established. The patient refused further
      diagnostic procedures and left hospital for winti treatment in Surinam. He did
      not take the prescribed pheneticillin and returned after seven weeks in a very
      poor condition. The second admission was complicated by septic shock. Despite
      intensive treatment he died. On autopsy actinomycosis abscesses were found in
      lung, liver and kidney. Even when suspected, an infection with Actinomyces is
      difficult to diagnose. Without adequate treatment this infection can lead to life
      threatening complications.

PMID- 9550817
TI  - [HIV/AIDS in The Netherlands: better treatment possibilities make HIV- instead of
      AIDS-surveillance necessary].

PMID- 9550818
TI  - [Joint decision making, how? Physician-patient communication on palliative
      chemotherapy].

PMID- 9550819
TI  - [Neurological presentation on non-Hodgkin lymphoma: a diagnostic problem].

PMID- 9550820
TI  - [Nerve circuit disorders: determination of polyneuropathy].
AB  - So many conditions, both hereditary and acquired, can lead to polyneuropathy that
      a systematic approach is needed to identify the cause. Finding a cause is
      necessary to inform the patient about prognosis, handicap and chances of
      treatment. Three patients with polyneuropathy are described. The first was a man
      aged 34 with a predominantly motor neuropathy who appeared to have a duplication
      in the pmp-22 gene on chromosome 17PII.2. The diagnosis was hereditary
      sensorimotor neuropathy type IA (hypertrophic form of Charcot-Marie-Tooth
      disease). The second was a woman of 58 years; she had a sensory polyneuropathy as
      the first manifestation of Hodgkin's disease. The last patient, a 67-year-old
      man, had polyneuropathy due to vasculitis. He showed a prompt response to
      treatment.

PMID- 9550821
TI  - [The necessity for centralization of pediatric intensive care].
AB  - Substantial evidence indicates that outcome of critically ill children, treated
      in tertiary paediatric intensive care units (PICUs) is superior to that of those
      treated in other settings. However, a significant number of children who require
      this level of care are not admitted to such a unit e.g. due to capacity
      constraints, reluctance of physicians of general hospitals to refer children to a
      tertiary centre, and transportation problems. Centralization of care, as recently
      proposed in the UK, is necessary in the Netherlands, as well, to improve the
      quality of care. This will require a controlled number of PICU beds in a
      restricted number of centres, adequate transport facilities and step-down or high
      dependency units in large general hospitals.

PMID- 9550822
TI  - [Polyneuropathy: diagnosis and management].
AB  - A polyneuropathy is characterized by a symmetrical distribution of sensory or
      motor abnormalities, more pronounced distally than proximally and usually more
      evident in the lower than in the upper limbs. Polyneuropathies may be classified
      on the basis of (a) clinical picture: acute/subacute/chronic,
      sensory/motor/autonomous, axonal degeneration/segmental demyelinization, and (b)
      cause: metabolic disorder, deficiency, infection, auto(dys)immunity, hereditary
      and toxic/iatrogenic polyneuropathy, with idiopathic polyneuropathy as the
      remaining group. Damaged nerves may recover as the result of spontaneous
      remyelinization and axonal regeneration. Treatment is particularly successful in
      immunomediated neuropathies. Withdrawal is often successful in intoxications and
      suppletion in deficiencies. Even if no treatment is possible, the diagnosis is
      important: the patient can be taught to accept his disease and the prognosis can
      be determined, in connection with possible handicaps.

PMID- 9550823
TI  - [Immunology in clinical practice. VII. Psoriasis].
AB  - A new hypothesis of the pathogenesis of psoriasis holds that psoriasis is an
      epidermal hyperproliferative disorder resulting from abnormal interaction between
      T cells and basal layer stem cell keratinocytes. New therapies aimed at reducing
      T cell activity are most successful, as exemplified by the efficacy of systemic
      cyclosporine in severe cases of psoriasis. New developments in immunogenetics and
      immunodermatology are anticipated and it is expected that they will fully explain
      the chain of pathological events.

PMID- 9550824
TI  - [Laboratory diagnosis of Lyme borreliosis].
AB  - Three stages can be observed in Lyme borreliosis: the acute stage (with dermal
      and systemic disease), an intermediate stage (with neurological and
      cardiovascular complaints and myositis), and a chronic stage (with arthritis, low
      back pain, dermatological and neurological complaints). If no acute stage with
      erythema chronicum migrans is seen, laboratory tests must provide the diagnosis.
      In the so-called two-test protocol at least two different tests must be positive
      for a definite diagnosis. Because culture is difficult, serology (demonstration
      of specific IgM and IgG antibodies against spirochaetal antigens) is the
      preferred technique. Cross reactions, antigenic variations and differences in
      antigenic expression in American and European strains may cause false-negative
      and false-positive results with the current tests. Moreover, previous use of
      antibiotics can interfere with the production of specific antibodies, and the
      effect of therapy is not correlated with height and behaviour of antibody titres.
      Additional investigation with immunoblot techniques, demonstrating specific
      antibody patterns may be valuable. An interesting alternative, not yet fully
      developed, is detection of specific antigens in tissues.

PMID- 9550825
TI  - [Referral of patients with polyneuropathy by the family physician: influence of
      type of symptoms but not of age].
AB  - OBJECTIVE: To investigate the influence of the age of the patient and the nature
      of a polyneuropathy on the referral behaviour of general practitioners (GPs).
      DESIGN: Written questionnaire sent to GPs regarding paper case records of
      polyneuropathy. SETTING: University Hospital Utrecht, the Netherlands. METHODS:
      1590 GPs were asked about their differential diagnosis regarding a paper case
      record of a patient with polyneuropathy. There were six case records, differing
      in age (53, 64 and 73 years) and nature of the disease (sensory or sensorimotor
      polyneuropathy). The GPs were divided into six groups with similar demographic
      characteristics and type of practice. To avoid focus on polyneuropathy, all GPs
      also received questions about three other neurological cases (amaurosis fugax,
      radicular syndrome and vasovagal collapse). RESULTS: The mean response of the
      questionnaire was 54% (n = 844). Most GPs diagnosed the polyneuropathy (analysis
      of variance; p < 0.0001). The age of the patient did not influence the diagnosis
      nor the referral behaviour. At least 73% of the patients with a sensory and 81%
      of the patients with a sensorimotor polyneuropathy were referred to neurologists
      for further investigations (chi(2)-test; p < 0.05). CONCLUSION: At least 73% of
      the GPs referred a patient with polyneuropathy to a neurologist; patients with
      muscle weakness were referred more often than patients with only sensory
      disturbances. Referral was not influenced by the age of the patient.

PMID- 9550826
TI  - [Nasopharyngeal carcinoma: epidemiology and treatment outcome].
AB  - OBJECTIVE: To determine epidemiology, symptoms and treatment results of patients
      with nasopharyngeal carcinoma. DESIGN: Descriptive and retrospective. SETTING:
      The Dutch Cancer Institute (Antoni van Leeuwenhoek Hospital), Amsterdam, the
      Netherlands. METHODS: The clinical, epidemiological and radiotherapy data of the
      129 patients with a nasopharyngeal carcinoma referred between 1977 and 1993 to
      our hospital were analysed. Twenty patients were referred for a second opinion
      only, presented with recurrent disease, or had received their treatment
      elsewhere. Data of 109 patients were analysed. RESULTS: During the last decade
      more patients born in Asia and North-Africa were referred (p = 0.0057), a total
      of 52 (48%) out of 109 referred patients. There were 62 (58%) patients in whom an
      enlarged cervical lymph node at level II (upper jugular group) was the presenting
      symptom. In 53 (50%) cases hearing loss due to otitis media with effusion was the
      first symptom. In 54 (54%) patients the delay between the first symptoms and
      diagnosis of carcinoma was > 20 weeks. 5-year survival was 48% (SE 6%) for the
      whole group (n = 109) of patients and 52% (SE 6%) for the patients treated with
      curative intent (n = 96). CONCLUSION: During the last decade the population of
      patients with nasopharyngeal carcinoma in the Netherlands contained more patients
      from Asia and North-Africa. Suspicious cervical lymph node swellings and (or)
      (unilateral) otitis media with effusion may be indicative of a nasopharyngeal
      carcinoma.

PMID- 9550827
TI  - [Ovarian vein thrombosis].
AB  - A 44 year-old woman was admitted with fever and lower abdominal pain at the right
      side suggestive of appendicitis. Ovarian vein thrombosis was diagnosed by
      sonography and confirmed by contrast-enhanced CT scan. After heparinisation the
      complaints disappeared and fever resolved in less than 72 hours. Repeated
      radiological investigation showed regression of the thrombus. Ovarian vein
      thrombosis is an uncommon, potentially fatal disorder that can be adequately
      treated with medication. The cornerstone of the diagnosis consists in non
      invasive radiological investigation.

PMID- 9550828
TI  - [Chronic fatigue syndrome].

PMID- 9550829
TI  - [Chronic fatigue syndrome].

PMID- 9550830
TI  - [Chronic fatigue syndrome].

PMID- 9550831
TI  - [Chronic fatigue syndrome].

PMID- 9550832
TI  - [Chronic fatigue syndrome].

PMID- 9550833
TI  - [Chronic fatigue syndrome].

PMID- 9550834
TI  - [Chronic fatigue syndrome].

PMID- 9550835
TI  - [Sore throat in rheumatoid arthritis; 2 patients with crico-arytenoid arthritis].

PMID- 9550836
TI  - [Left ventricular hypertrophy; differences in diagnostic and prognostic value of
      electrocardiography and echocardiography].

PMID- 9550837
TI  - [Suppurative hidradenitis].

PMID- 9550839
TI  - [The use of drugs to improve athletic performance].

PMID- 9550840
TI  - Extracting findings from narrative reports: software transferability and sources
      of physician disagreement.
AB  - While natural language processing systems are beginning to see clinical use, it
      remains unclear whether they can be disseminated effectively through the health
      care community. MedLEE, a general-purpose natural language processor developed
      for Columbia-Presbyterian Medical Center, was compared to physicians' ability to
      detect seven clinical conditions in 200 Brigham and Women's Hospital chest
      radiograph reports. Using the system on the new institution's reports resulted in
      a small but measurable drop in performance (it was distinguishable from
      physicians at p = 0.011). By making adjustments to the interpretation of the
      processor's coded output (without changing the processor itself), local behavior
      was better accommodated, and performance improved so that it was
      indistinguishable from the physicians. Pairs of physicians disagreed on at least
      one condition for 22% of reports; the source of disagreement appeared to be
      interpretation of findings, gauging likelihood and degree of disease, and coding
      errors.

PMID- 9550841
TI  - Cooperative problem solving with personal mobile information tools in hospitals.
AB  - Health-care professionals have a broad range of needs for information and
      cooperation while working at different points of care (e.g., outpatient
      departments, wards, and functional units such as operating theaters). Patient
      related data and medical knowledge have to be widely available to support high
      quality patient care. Furthermore, due to the increased specialization of health
      care professionals, efficient collaboration is required. Personal mobile
      information tools have a considerable potential to realize almost ubiquitous
      information and collaborative support. They enable to unite the functionality of
      conventional tools such as paper forms, dictating machines, and pagers into one
      tool. Moreover, they can extend the support already provided by clinical
      workstations. An approach is described for the integration of mobile information
      tools with heterogeneous hospital information systems. This approach includes
      identification of functions which should be provided on mobile tools. Major
      functions are the presentation of medical records and reports, electronic mailing
      to support interpersonal communication, and the provision of editors for
      structured clinical documentation. To realize those functions on mobile tools, we
      propose a document-based client-server architecture that enables mobile
      information tools to interoperate with existing computer-based application
      systems. Open application systems and powerful, partially wireless, hospital-wide
      networks are the prerequisites for the introduction of mobile information tools.

PMID- 9550842
TI  - An integrated approach for a knowledge-based clinical workstation: architecture
      and experience.
AB  - Today, the demand for medical decision support to improve the quality of patient
      care and to reduce costs in health services is generally recognized.
      Nevertheless, decision support is not yet established in daily routine within
      hospital information systems which often show a heterogeneous architecture but
      offer possibilities of interoperability. Currently, the integration of decision
      support functions into clinical workstations is the most promising way.
      Therefore, we first discuss aspects of integrating decision support into clinical
      workstations including clinical needs, integration of database and knowledge
      base, knowledge sharing and reuse and the role of standardized terminology. In
      addition, we draw up functional requirements to support the physician dealing
      with patient care, medical research and administrative tasks. As a consequence,
      we propose a general architecture of an integrated knowledge-based clinical
      workstation. Based on an example application we discuss our experiences
      concerning clinical applicability and relevance. We show that, although our
      approach promotes the integration of decision support into hospital information
      systems, the success of decision support depends above all on an adequate
      transformation of clinical needs.

PMID- 9550843
TI  - Analysis of data associated with seemingly temporal clustering of a rare disease.
AB  - Three statistical tests aimed at detecting temporal clustering within a given
      short series of diagnoses are presented. These tests are based on a standardized
      time interval between consecutive diagnoses. Two of the tests (the Cuscore and
      the Sets tests) are derived from sequential monitoring techniques which are
      sensitive to temporal clustering within the data set. The third test (R test) is
      not sequential and its sensitivity is focused on the average increase in the
      overall rate of the disease rather than on clustering within the series. Power
      curves are presented for conditions related to the intensity level of the subtle
      epidemic, the cluster size and the number of diagnoses. None of the techniques
      showed highest efficiency over all the specified conditions. The R test is the
      most efficient when the relative risk is 2 or less, and the Cuscore test is the
      most efficient method when the relative risk is > or = 2.5.

PMID- 9550844
TI  - Determining first admissions in a hospital discharge file via record linkage.
AB  - The aim of this study was to identify first admissions in a public hospital
      discharge file with the greatest possible accuracy. Computerised data linkage was
      used to link injury events. This involved the use of "internal" data linkage
      (unduplication) which, in data linkage terms, is equivalent to matching two
      identical files. Admission status indicators obtained from deterministic and
      probabilistic linkages were compared with those obtained from a manual review.
      Small absolute reductions in error were obtained using a probabilistic linkage
      over a deterministic linkage. However, these reflected large relative reductions
      in error. A validity check confirmed initial results and discounted against
      possible bias due to the subjective nature of the probabilistic linking
      procedure.

PMID- 9550845
TI  - Indicators for the automated analysis of drug prescribing quality.
AB  - Irrational and inconsistent drug prescription has considerable impact on
      morbidity, mortality, health service utilization, and community burden. However,
      few studies have addressed the methodology of processing the information
      contained in these drug orders used to study the quality of drug prescriptions
      and prescriber behavior. We present a comprehensive set of quantitative
      indicators for the quality of drug prescriptions which can be derived from a drug
      order. These indicators were constructed using explicit a priori criteria which
      were previously validated on the basis of scientific data. Automatic computation
      is straightforward, using a relational database system, such that large sets of
      prescriptions can be processed with minimal human effort. We illustrate the
      feasibility and value of this approach by using a large set of 23,000
      prescriptions for several diseases, selected from a nationally representative
      prescriptions database. Our study may result in direct and wide applications in
      the epidemiology of medical practice and in quality control procedures.

PMID- 9550846
TI  - Object-oriented modeling and terminologies for drug contraindications.
AB  - There is no available standardized representation of contraindications that can
      be used in drug knowledge bases. In this paper, an object-oriented representation
      of contraindications is proposed that would allow computerized checking of drug
      prescription safety. It distinguishes four types of contraindications:
      pathological state, physiological state, findings of investigation procedures,
      and diagnostic or therapeutic procedures. The vocabulary usable for expressing
      the contraindications appropriate for automated prescription checking was also
      investigated. ICD10 (International Classification of Diseases, tenth revision),
      SNOMED III (Systematized Nomenclature of Medicine), ICPC (International
      Classification of Primary Care), and ATC (Anatomic Therapeutic and Chemical
      Classification) were studied as potential sources of standardized vocabulary. A
      system to support entering data on contraindications into a drug knowledge base,
      compatible with the proposed structure and using the identified vocabulary
      sources, is also presented.

PMID- 9550847
TI  - Randomized observational studies on the economics of therapies--biometrical
      experience of two trials.
AB  - Economic studies in medicine are intended to investigate costs, associated with a
      particular problem dealing with the indication, diagnosis or therapy, for
      instance, whether the high costs involved in a highly intensive or innovative
      therapy could be balanced by the eventual savings made, due to the shorter
      periods of treatment. In such situations a randomized controlled trial is
      necessary to find out which therapy or which therapeutical strategy is least
      expensive in the long run. Economic studies do, however, present some specific
      problems. Making a list of all the cost-relevant treatment items can be very
      laborious, but the use of flat rates and lump sums alone cannot lead to a
      complete cost analysis. Often, costs between hospitals vary more than between
      treatment regimens. Early and sudden deaths incur low costs and may bias the
      results. Furthermore, costs are distributed with a long and heavy upper tail
      including extreme outliers. This does, in fact, complicate the estimation of the
      sample size. In this article, these problems are outlined and, with the help of
      the data obtained from two randomized economic trials in health care, solutions
      are proposed and discussed.

PMID- 9550848
TI  - Diagnosis of acute appendicitis in two databases. Evaluation of different
      neighborhoods with an LVQ neural network.
AB  - The use of an artificial neural network system was studied in the diagnosis of
      acute abdominal pain, especially acute appendicitis, with patients from Finland
      and Germany. Separate Learning Vector Quantization (LVQ) neural networks were
      trained with a training set from each database and also with a combined database.
      Each neural network was evaluated separately with a test set of cases from each
      database. With the combined database different neighborhood methods were compared
      to find the optimal choice for this decision-making problem. The acute
      appendicitis cases of the Finnish test data set were classified well with all the
      networks, but the cases of the German test set were difficult to classify for the
      Finnish network. The use of larger neighborhoods increased the sensitivity of the
      classification by nearly 10%. The differences in the results of the Finnish and
      German databases suggest that there are differences in the data collection or
      patient populations between centers. Therefore, care must be taken when using
      decision-support systems which have been developed in other centers. Neural
      networks offer a method to evaluate differences between databases. With the use
      of larger neighborhoods, the effects of the differences on the accuracy of the
      classification can be partly diminished.

PMID- 9550849
TI  - Best-link matching of Scottish health data sets.
AB  - Methods are described used to link the Community Health Index and the National
      Health Service Central Register (NHSCR) in Scotland to provide a basis for a
      national patient index. The linkage used a combination of deterministic and
      probability matching techniques. A best-link principle was used by which each
      Community Health Index record was allowed to link only to the NHSCR record with
      which it achieved the highest match weight. This strategy, applied in the context
      of two files which each covered virtually the entire population of Scotland,
      increased the accuracy of linkage approximately a thousand-fold compared with the
      likely results of a less structured probability matching approach. By this means,
      98.8% of linkable records were linked automatically with a sufficient degree of
      confidence for administrative purposes.

PMID- 9550850
TI  - Effects of record linkage errors on disease registration.
AB  - Reliable record linkage is a prerequisite for high-quality population-based
      disease registration. Rapid developments in computer processing have made record
      linkage both more efficient and more reliable in recent years. At the same time,
      concerns about confidentiality increasingly hinder record linkage in many disease
      registries. This paper provides basic algebraic models describing the effects of
      record linkage errors on monitoring disease incidence. Homonym errors, that is,
      erroneous linkage of records that pertain to distinct individuals, lead to
      underestimation of incidence in the registry population. The degree of
      underestimation strongly depends on the discriminating power of personal
      identifiers and the record linkage procedure on the one hand, and the number of
      registered cases on the other hand. Synonym errors, that is, failure to link
      notifications on the same individual, lead to overestimation of incidence in the
      population base. The combined effects of record linkage errors are illustrated
      with empirical examples. We conclude that it is the largest and most informative
      disease registries that are potentially affected most by impediments of record
      linkage procedures due to unduly restrictive confidentiality rules.

PMID- 9550851
TI  - Towards a national patient card system in Japan.
AB  - Patient Card Systems (PCS) have been applied on a regional level to improve
      access to patient information. However, current projects lack a vision of future
      integration on a national level. In addition, Integrated Circuit cards and
      optical cards were introduced without considering that their cost and capacity
      limits impose significant constraints for future integration. The major arguments
      against PCS are the huge costs incurred by such a system and the limitations of
      the card capacities. In addition, standards and legislation have not been
      sufficiently developed. In this study, we propose a new model of PCS that employs
      recent communication and card technologies as a key to access a national medical
      information center. We demonstrate that PCS are feasible if implemented in
      several distinct phases and if the acceptance and cooperation of physicians and
      patients are achieved. However, political consensus about the necessity of reform
      in the health care sector must be established so that the necessary legislation
      can be enacted.

PMID- 9550852
TI  - Review of biomedical knowledge and data representation with conceptual graphs.
AB  - The basis of conceptual graphs theory is an ontology of types of concepts.
      Concepts issued from the ontology are interlinked by semantic relationships and
      constitute canonical conceptual graphs. Canonical graphs may be combined to
      derive new conceptual graphs by means of formation rules. This formalism allows
      to separate knowledge representation into a conceptual level and a domain
      dependent level, and enables to share and reuse a representation. This paper
      presents conceptual graph applications to biomedical data and concept
      representation, classification systems, information retrieval, and natural
      language understanding and processing. A discussion on the unifying role
      conceptual graphs theory plays in the implementation of knowledge-based systems
      is also presented.

PMID- 9550853
TI  - The LYMFASIM simulation program for modeling lymphatic filariasis and its
      control.
AB  - The LYMFASIM modeling framework for the transmission and control of the tropical
      parasitic disease lymphatic filariasis is described and its use in the context of
      an endemic community in north-eastern Brazil is illustrated. Lymphatic filariasis
      is a disease with a complex natural history with many unknowns. This complicates
      decision making with respect to control strategies. With LYMFASIM, a variety of
      hypotheses can be tested about the life history of the parasite Wuchereria
      bancrofti, its transmission from man to man through mosquitoes, the role of the
      immune system in regulating parasite numbers, the development of disease
      symptoms, and the effects of control measures (drug treatment or mosquito
      control). The implications of alternative assumptions and uncertainty about the
      quantification of parameters for the effectiveness of control strategies can be
      investigated. Thanks to the use of stochastic microsimulation, LYMFASIM is highly
      flexible and can be adapted and extended as new knowledge emerges.

PMID- 9550854
TI  - Towards the unification of inference structures in medical diagnostic tasks.
AB  - The central purpose of artificial intelligence applied to medicine is to develop
      models for diagnosis and therapy planning at the knowledge level, in the Newell
      sense, and software environments to facilitate the reduction of these models to
      the symbol level. The usual methodology (KADS, Common-KADS, GAMES, HELIOS,
      Protege, etc) has been to develop libraries of generic tasks and reusable problem
      solving methods with explicit ontologies. The principal problem which clinicians
      have with these methodological developments concerns the diversity and complexity
      of new terms whose meaning is not sufficiently clear, precise, unambiguous and
      consensual for them to be accessible in the daily clinical environment. As a
      contribution to the solution of this problem, we develop in this article the
      conjecture that one inference structure is enough to describe the set of analysis
      tasks associated with medical diagnoses. To this end, we first propose a
      modification of the systematic diagnostic inference scheme to obtain an analysis
      generic task and then compare it with the monitoring and the heuristic
      classification task inference schemes using as comparison criteria the
      compatibility of domain roles (data structures), the similarity in the
      inferences, and the commonality in the set of assumptions which underlie the
      functionally equivalent models. The equivalences proposed are illustrated with
      several examples. Note that though our ongoing work aims to simplify the
      methodology and to increase the precision of the terms used, the proposal
      presented here should be viewed more in the nature of a conjecture.

PMID- 9550855
TI  - Implementing HL7: from the standard's specification to production application.
AB  - A C++ implementation of the HL7 health-care data interchange standard was
      developed by automatic methods applied to the authoritative specification of the
      standard. The reusable class library thus created presents an intuitive,
      flexible, and easy-to-use application programming interface to the HL7 protocol.
      This allows HL7 applications to be developed quickly while a high conformance to
      the standard is ensured.

PMID- 9550856
TI  - Physiological determinants of quality of life.

PMID- 9550857
TI  - Assessing quality of life in respiratory disorders: chronic nonspecific lung
      disease.

PMID- 9550858
TI  - Quality of life and chronic respiratory failure.

PMID- 9550859
TI  - An overview of recent overviews in the treatment of non-small cell lung cancer.

PMID- 9550860
TI  - Neo-adjuvant chemotherapy prior to surgery in stage III non-small cell lung
      cancer.

PMID- 9550861
TI  - New prognostic factors in lung cancer.

PMID- 9550862
TI  - Involvement of N-components in lung cancer.

PMID- 9550863
TI  - The role of radiotherapy in the management of patients with small cell lung
      cancer.

PMID- 9550864
TI  - Management of idiopathic pulmonary fibrosis: prognostic indicators.
AB  - There now exists a number of approaches that can be used to predict likely
      responses to therapy and disease progression in idiopathic pulmonary fibrosis.
      These tools should be used in management decisions. It must be remembered that
      destroyed, fixed fibrotic lung will not improve and that the computed tomography
      pattern and extent of the "fibrotic" pattern should be used to determine if the
      best response to treatment that can be expected is a prevention of deterioration
      rather than improvement.

PMID- 9550865
TI  - Medical treatment for idiopathic pulmonary fibrosis.

PMID- 9550866
TI  - Patient-ventilator interaction.

PMID- 9550867
TI  - Acute severe asthma and treatment: a gas exchange perspective.

PMID- 9550868
TI  - Acute respiratory failure: pulmonary thromboembolism.

PMID- 9550869
TI  - Differential diagnosis of fever and pulmonary densities in mechanically
      ventilated patients.

PMID- 9550870
TI  - Advanced chronic obstructive pulmonary disease.

PMID- 9550871
TI  - Epithelial adhesion molecules in airway repair.

PMID- 9550872
TI  - Mechanisms of damage in COPD.

PMID- 9550873
TI  - The functional consequences of airway remodeling in asthma.
AB  - Structural changes in the airway walls involving extracellular matrix remodelling
      are prominent features of asthma. These changes are probably driven by mediators
      released as a consequence of chronic allergic inflammation. It is clear that
      changes in the extracellular matrix have the capacity to influence airway
      function in asthma. However, it is not clear how each of the many changes that
      occur in the airway wall contribute to altered airway function in asthma.
      Collagen deposition in the subepithelial matrix, and hyaluronan and versican
      deposition around and internal to the smooth muscle would be expected to oppose
      the effect of smooth muscle contraction. Conversely, geometric considerations
      would result in exaggerated airway narrowing for a given degree of smooth muscle
      shortening, as the airway wall is thickened by the deposition of these molecules
      internal to the smooth muscle. Elastin and cartilage reorganization and
      degradation in the airway walls would be expected to result in decreased airway
      wall stiffness and increased airway narrowing for a given amount of force
      generated by the smooth muscle. Degradation of matrix associated with the smooth
      muscle may both decrease the stiffness of the parallel elastic component and
      uncouple smooth muscle from the load provided by lung recoil, allowing
      exaggerated smooth muscle shortening. Increase in muscle mass may be associated
      with an increase, a decrease or no change in smooth muscle contractility. If an
      increase in muscle mass was associated with preservation of its contractile
      capacity modelling studies suggest that it could be the most important
      contributor to exaggerated airway narrowing. Modelling studies also suggest that
      the pattern of mucosal folding during smooth muscle contraction may be an
      important determinant of airway narrowing. The greater the number of folds, and
      the stiffer the subepithelial collagenous layer the more resistant the airway
      will be to narrowing.

PMID- 9550874
TI  - Airway structure to function relationships in asthma and COPD.

PMID- 9550875
TI  - Report of the National Institutes of Health (NIH) Workshop on the Development of
      Research Priorities in Eating Disorders.
AB  - The National Institutes of Health (NIH) Workshop on the Development of Research
      Priorities in Eating Disorders was convened in New York on April 24 and 25, 1996.
      The goals of the workshop were (1) to identify important unanswered questions in
      the study and treatment of eating disorders, (2) to discuss potentially fruitful
      approaches to answering these questions through basic and clinical research, and
      (3) to assist the NIH and other funding agencies in assigning priorities for
      research on eating disorders. The program consisted of a series of brief
      presentations by moderators, each followed by facilitated discussion of the topic
      with members of the audience. Three reporters (CMG, MJD, FMC) took detailed notes
      of the proceedings, which have been incorporated into this article. A summary of
      this workshop is presented, along with recommendations for future research that
      were identified by workshop participants.

PMID- 9550876
TI  - Anorexia nervosa, obsessional behavior, and serotonin.
AB  - Although many women diet, relatively few develop the extreme weight loss and the
      clinical symptoms of anorexia nervosa. An underlying biological diathesis and
      temperament may place someone at risk for developing anorexia nervosa. Certain
      traits, such as negative affect, behavioral inhibition, compliance, high harm
      avoidance, and an obsessive concern with symmetry, exactness, and perfectionism,
      persist after recovery from anorexia nervosa. These persistent symptoms raise the
      possibility that such traits exist premorbidly and contribute to the pathogenesis
      of this disorder. Such traits could be associated with increased brain serotonin
      activity. After recovery, anorexics have increased levels of 5-HIAA, the major
      metabolite of serotonin, in the cerebrospinal fluid (CSF). Low CSF 5-HIAA levels
      have been associated with impulsive and aggressive behaviors, which are opposite
      to those typically found in anorexia nervosa. Increased serotonin activity could
      contribute to many behavioral symptoms, such as increased satiety. Moreover,
      recent data suggest that selective serotonin reuptake inhibitor (SSRI)-type
      medication improves outcome and prevents relapse in people with anorexia nervosa.
      These theoretical issues have important clinical implications in this era of
      diminished support for treatment of eating disorders. Anorexia nervosa, like
      other major psychiatric disorders, has contributory pathophysiology and can
      benefit from and deserves appropriate treatment resources.

PMID- 9550877
TI  - Research update on serotonin function in bulimia nervosa and anorexia nervosa.
AB  - The extent to which dysregulation of serotonin function in the central nervous
      system may contribute to core symptoms in patients with bulimia nervosa and
      anorexia nervosa is currently an area of intensive psychobiological
      investigation. Preclinical and clinical studies have demonstrated the involvement
      of the neurotransmitter serotonin in the regulation of food intake, suggesting
      that impaired serotonin-mediated satiety signals could contribute to patterns of
      recurrent binge eating. Other symptom patterns in patients with eating disorders,
      including mood dysregulation, impulsivity, and obsessionality, as well as
      therapeutic response to serotonergic agents, suggest involvement of serotonergic
      pathways. With a primary focus on serotonin function, this article reviews
      clinical studies of neuroendocrine and behavioral response to pharmacological
      challenges, levels of neurotransmitter metabolite in cerebrospinal fluid, and
      platelet studies. Controlled clinical trials involving pharmacological treatment
      with serotonergic medications are summarized. Considerations for future research
      are discussed.

PMID- 9550878
TI  - Behavior genetics and eating disorders.
AB  - Behavior genetics is concerned with the genetic and environmental influences on
      individual differences in the vulnerability to eating disorders. We should be
      skeptical about simple genetic explanations for disorders whose development,
      maintenance, and possible remission involve the interaction of individual
      behaviors and environmental circumstances. Twin, family, and adoption studies can
      help to delineate which phenotypes are most heritable, and which are most
      responsive to family circumstances or individual environments. Subsequent
      searches for individual genetic and environmental risk factors can be guided by
      these results. Although there is consistent evidence of genetic factors
      influencing vulnerability to eating disorders, the details are far from clear,
      and additional studies will be useful. The further development of dimensional
      indices of vulnerability will improve population-based and developmental genetic
      research, as well as facilitating the search for individual genes.

PMID- 9550879
TI  - Issues in mapping genes for eating disorders.
AB  - Recent twin studies show that both genetic and environmental factors contribute
      to the development of eating disorders. As in many other fields, there is much
      enthusiasm regarding the possibility of locating the specific genes that
      influence the risk of eating disorders. Advances in molecular and statistical
      technology have made this task more feasible than it was in the past, and
      continued enhancements in new technology are expected in the future. Despite
      these advances, the resources required to map a gene for traits as complex as
      eating disorders are likely to be enormous. Researchers considering such an
      undertaking may wish to look for ways to reduce this demand, such as (1) using
      multivariate analyses, (2) studying intermediate quantitative phenotypes, (3)
      using large sibships, (4) analytic enhancements (e.g., multipoint analyses), (5)
      reconceptualizing power, (6) data pooling, and (7) disequilibrium mapping.

PMID- 9550880
TI  - Diagnostic criteria for eating disorders: current concerns and future directions.
AB  - This article is a critical review of the evolution of diagnostic criteria for
      anorexia nervosa, bulimia nervosa, and binge eating disorder. The shortcomings of
      the current diagnostic criteria for all three disorders are addressed, as are the
      primary nosological challenges facing the field.

PMID- 9550881
TI  - Eating behavior and eating disorders: the interface between clinical research and
      clinical practice.
AB  - Cognitive-behavioral therapy (CBT) has been shown to be a highly effective form
      of treatment for patients with bulimia nervosa and anorexia nervosa. Issues of
      satiety disturbances, food restriction, and food choice are central to this form
      of therapy; however, ingestive behavior research that directly addresses these
      issues in eating disorder patients has often been overlooked by clinicians. These
      areas of research are reviewed and the implications of the findings for more
      effective CBT therapy with anorexics and bulimics are discussed.

PMID- 9550882
TI  - Eating disorders and comorbidity: empirical, conceptual, and clinical
      implications.
AB  - The most common major comorbid disorders associated with eating disorders include
      substance use disorders, personality disorders, mood disorders, anxiety
      disorders, and obesity. To test conceptual models of the relationship between the
      eating disorders and these comorbid disorders, complex research paradigms are
      needed, including epidemiological studies, behavior-genetic studies, and
      longitudinal research designs. Comorbidity may be a significant factor to
      consider as approaches to the treatment of eating disorders continue to evolve.

PMID- 9550883
TI  - Males with eating disorders: challenges for treatment and research.
AB  - Males represent only 10 percent of eating disorder cases. This gender discrepancy
      is among the most extreme in psychiatry and medicine. Determining what
      differences in etiology and mechanism best explain the discrepancy presents an
      intellectual challenge. Beginning at about the third grade, boys and girls
      diverge in social development. Boys show significantly less desire to lose
      weight, express dissatisfaction with the upper rather than the lower body, and
      use dieting to achieve specific external goals rather than as a cultural norm.
      Males reach a significantly higher body mass index (BMI) than females do before
      they beginning dieting. (27.2 versus 24.3, p < .01). While overall treatment
      principles are similar, males in treatment require attainment of a different
      hormonal milieu (testosterone), attention to past and future sexual role,
      amelioration of perception of stigma, and preparation for return to male social
      roles. Males and females suffer comparable degrees of osteopenia and brain
      shrinkage during anorexia nervosa. The effectiveness of antidepressants in males
      with eating disorders (compared with that in females) has not been well studied.
      Male gender is not an adverse factor in short-term or long-term treatment
      outcome. Understanding the lower frequency of these illnesses in males may lead
      to more effective means of protecting girls from eating disorders and from the
      culturally induced distress about normal body size and shape that burdens
      adolescent development and adult life.

PMID- 9550884
TI  - Mechanisms and treatment options for bone loss in anorexia nervosa.
AB  - Osteoporosis is present in over half of all patients with anorexia nervosa. Bone
      loss often occurs at a young age and may persist even after recovery,
      predisposing patients to debilitating spinal crush fractures. The pathogenesis of
      bone loss in anorexia nervosa is not completely understood and may result from a
      number of mechanisms, including estrogen deficiency, inadequate vitamin and
      calcium intake, and nutritional effects on bone formation. Recent studies
      demonstrate that estrogen itself is inadequate to increase bone density in a
      majority of patients with anorexia nervosa and suggest that nutritionally
      dependent factors such as insulin-like growth factor-I (IGF-I), a potent bone
      trophic hormone, may be important in maintaining bone mass. IT is hoped that new
      anabolic strategies to increase osteoblast function will become available in the
      future. In the interim, weight gain, restoration of gonadal function, and calcium
      supplementation remain the cornerstones of treatment in this disease.

PMID- 9550885
TI  - The future of risk factor research in understanding the etiology of eating
      disorders.
AB  - This article explores whether particular risk factors are best seen as precursors
      or as symptoms. Psychological, cultural, family, developmental, and biological
      risk domains that may be important in the etiology of eating disorders are
      briefly reviewed. We describe a 4-year prospective study assessing a wide range
      of risk factors for development of eating disorders in a large school-based
      sample of adolescents. For subjects who were relatively asymptomatic, a
      personality or temperamental characteristic of negative affect/esteem measured at
      study entrance was the only significant predictor of later risk score for both
      girls and boys. The significant comorbidity demonstrated in a separate group that
      had high risk for eating disorders suggests that negative affectivity may be a
      vulnerability factor for overall psychopathology rather than a predisposition
      specifically for eating disorders. Following subjects through the young-adult
      years and later may further clarify the range of influences affecting disordered
      eating. Primary prevention and early intervention programs in the schools are
      also recommended.

PMID- 9550886
TI  - Priorities in prevention research for eating disorders.
AB  - This article discusses potential areas for research in the prevention of eating
      disorders. Prevention research encompasses a large range of activities; reviews
      are available (Crisp 1988; Shisslak et al. 1987; USDHHS/McKnight 1996). This
      article focuses on school-based primary preventive interventions.

PMID- 9550887
TI  - Prevention of eating disorders: directions for future research.

PMID- 9550888
TI  - Does adjunctive fluoxetine influence the post-hospital course of restrictor-type
      anorexia nervosa? A 24-month prospective, longitudinal followup and comparison
      with historical controls.
AB  - A 24-month naturalistic, prospective longitudinal followup study was conducted on
      33 patients with anorexia nervosa who had participated in an intensive,
      multidisciplinary inpatient treatment program and were receiving fluoxetine as
      part of their continuing treatment regimen. Data on course, outcome, and
      treatment exposure in this cohort were obtained using standardized, comprehensive
      interviews administered at 6-month intervals after hospital discharge.
      Longitudinal course data for these patients were compared with data for matched
      historical controls who had received identical inpatient and followup treatment
      but without adjunctive fluoxetine. Analyses failed to show that fluoxetine had a
      significant effect on the cumulative probability of remaining at target weight
      during the followup period, the risk of sustained weight loss, or other clinical
      measures of outcome. Thus, adjunctive treatment with fluoxetine may not have
      additive long-term therapeutic benefit when measured against the effects of
      sustained and intensive followup treatment.

PMID- 9550889
TI  - Pharmacotherapy of bulimia nervosa and binge eating disorder: longer-term
      outcomes.
AB  - The longer-term effects of antidepressant medication, with and without the
      addition of psychotherapy, for the treatment of bulimia nervosa and binge eating
      disorder are reviewed. The use of a single antidepressant agent results in
      recovery of about 25 percent of patients entering treatment; continued treatment
      is accompanied by relapse in about one-third of these patients. Substituting one
      or more antidepressants for the initial agent in patients who fail to improve or
      cannot tolerate side effects improves long-term maintenance. Adding cognitive
      behavioral therapy (CBT) may prevent relapse once medication is discontinued, and
      the combination of CBT and antidepressant treatment is more effective than a
      single medication. There is also evidence that antidepressant treatment combined
      with CBT is more effective than placebo plus CBT. The problem of how to sequence
      medication and CBT has not been resolved, although a recent study demonstrating
      that pharmacotherapy is more cost-effective than CBT suggests that treatment
      might begin with medication.

PMID- 9550890
TI  - Psychological treatment of bulimia nervosa and binge eating disorder.
AB  - The field of eating disorders has grown rapidly, amassing an impressive body of
      treatment research in the past 20 years. In particular, researchers have focused
      on binge eating problems, which include bulimia nervosa (BN) and the more
      recently recognized binge eating disorder (BED). Numerous controlled treatment
      trials have shown cognitive-behavioral therapy (CBT) to be equally or more
      efficacious than any other BN treatment to which it has been compared. Although
      CBT also seems to be effective for BED, research is in a preliminary stage.
      Further combinations and adaptations of treatments for BED are needed to address
      the additional problem of obesity in this population. Preliminary data suggest
      that behavioral weight control treatment for BED is effective in reducing binge
      eating, and it may have the added benefit of weight loss. Interpersonal
      psychotherapy (IPT), the combination of CBT and medication, and self-help manuals
      are promising treatment alternatives for both BN and BED. Future treatment trials
      should include longer-term followup periods and more consistent definitions of
      successful treatment outcome. In addition, further study is needed in the areas
      of treatment nonresponders, pre-treatment predictors, a stepped-care treatment
      model, and methods for a wider dissemination of validated treatments.

PMID- 9550891
TI  - RAYS 22,2,1997 the new frontiers of functional radiology of the lung.

PMID- 9550892
TI  - The diabetic foot: epidemiology.
AB  - The epidemiology of the diabetic foot is still unknown because this heterogeneous
      pathologic condition is non uniformly classified and described. Lower limb
      peripheral vascular disease has a preferential distal location strongly
      associated with the classical factors of cardiovascular risk. Ulcers occur in 15%
      of diabetics and 6-20% of all hospitalized diabetic patients are affected by
      ulcers of the foot. There is a predictive feature of the severity of the ulcer in
      relation to its location. In the USA, ischemia-related amputations are about 200
      per million per year for non diabetics as against 3900 per million for diabetics;
      furthermore the incidence of a second amputation rises to 51% 5 years after first
      amputation. Risk factors for amputation are: smoking, hypertension, dyslipidemia,
      elderly age, glycosylated hemoglobin levels. Although mortality has decreased in
      the last 50 years, the diabetic foot is still a huge economic problem.

PMID- 9550893
TI  - Charcot's foot.
AB  - Diabetic osteoarthropathy is a chronic progressive arthropathy involving the
      bones and joints being constantly associated to somatic and autonomic peripheral
      neuropathy. The pathogenesis is related to sensory and motor neuropathy with
      morphologic foot alterations, relaxation and abnormal position on walking till
      complete collapse of the foot shown by the depressed longitudinal medial arch.
      Bone reabsorption due to osteoclasis and increased blood flow until osteomalacia
      appears, is characteristic of this arthropathy. The clinical features vary
      according to the location and severity of articular impairment and the stage of
      identification. The metatarsophalangeal or tarsometatarsal joint may be involved.
      The typical manifestation of Charcot's foot is plantar ulcer of variable location
      according to the weight-bearing area. Treatment tends to reduce the abnormal
      stress predisposing to ulceration with tailored footwear and orthoses.

PMID- 9550894
TI  - Lower limb ischemia.
AB  - Diabetes mellitus is the major cause of nontraumatic amputations in the
      industrialized countries. In 1980 the scientific societies of diabetology and the
      patients' associations subscribed at St. Vincent a declaration together with the
      WHO, where a 50% decrease in amputations was among the primary objectives of
      clinical diabetology. The main cause of amputations is foot ischemia related to
      obliterating peripheral arterial disease, more diffuse and severe in diabetics,
      typically affecting the infrapopliteal vessels. Clinical patterns of foot
      ischemia include superficial necrotic areas and gangrene involving the entire
      foot with necrosis of all anatomic planes. Infection is a common complication
      with a negative impact on prognosis. Definitive treatment of ischemia is achieved
      with revascularization which at present due to the advances in diagnostic
      procedures can be performed in diabetics with the same effectiveness observed in
      non diabetics.

PMID- 9550895
TI  - Infection of the diabetic foot.
AB  - Infection may be the first manifestation of the diabetic foot or may complicate a
      preexisting lesion. The increased susceptibility to infections of diabetics and
      the particular anatomy of the foot make infections particularly severe and
      rapidly progressive. The etiology is generally polymicrobial and a swab for
      culture of microorganisms is immediately required to plan correct and adequate
      antibiotic therapy based on the antibiotic sensitivity test. Infections can be
      treated in specialized outpatient services, while hospitalization is reserved to
      most severe cases with systemic manifestations. These specialized centers have
      been shown to be the only structures able to decrease the frequency, severity and
      recurrence of foot infections as well as their prevention.

PMID- 9550896
TI  - Diagnostic imaging of the diabetic foot.
AB  - Diagnostic imaging plays a major role in the osteoarticular disease of the foot
      in diabetics, allowing the diagnosis and evaluation of alterations for therapy
      planning. To-date conventional radiology is still of first choice in the study of
      the diabetic foot with the evaluation of osteoarticular damage caused by
      neuropathy and vascular disease. Major radiographic patterns are neuroarthropathy
      and osteomyelitis. Main locations are at the level of forefoot and less
      frequently of tarsus and tibiotarsal joint. Second choice procedures as US, CT
      and MRI are useful for a more accurate evaluation of soft tissue lesions and
      articular structures. US is the first choice procedure in soft tissue evaluation
      to rule out the presence of abscesses which require surgery. MRI with some
      limitations represents the gold standard for the study of joints and medullary
      disease. Spiral CT though less specific and sensitive than MRI for soft tissue
      and bone marrow study is still the exam of reference for the study of bone
      structures with three-dimensional reconstructions useful to plan orthopedic
      surgery.

PMID- 9550897
TI  - The diabetic foot: role of color-Doppler US.
AB  - Color Doppler US is a first choice instrumental exam for the diagnosis and
      staging of peripheral arterial occlusive disease in diabetic patients. Normal and
      pathological findings are analyzed to establish the potential and limitations of
      the procedure. Color Doppler US is a noninvasive, reproducible and cost-effective
      procedure. Direct morphologic and flowmetric evaluations of stenotic-occlusive
      alterations, and indirect evaluations based on the interpretation of velocimetry
      findings proximal and distal to the lesions, are feasible. The conventional basic
      exam can be enhanced with the power module. Encouraging experimental results are
      observed with the use of echographic contrast media. Disadvantages of the
      procedure are related to the poor panoramic view, subjective (operator-dependent)
      interpretation and limitations related to the physics of ultrasound.

PMID- 9550898
TI  - Angiography and MR-angiography in the diagnosis of peripheral arterial occlusive
      disease in diabetic patients.
AB  - An invasive diagnostic procedure as angiography which involves direct arterial
      injection of contrast through suitable catheters, is still considered the gold
      standard in the evaluation of diabetic patients with peripheral arterial
      occlusive disease. The accuracy of anatomical details is combined on angiography
      with a pan view, indispensable for correct therapeutic planning. MR-angiography,
      with the 2D time of flight sequences in particular, supplies images of great
      anatomical accuracy and very sensitive in the detection of occlusive lesions
      which compare well with angiography and superior in the assessment of the length
      of occluded tracts. This noninvasive, cost-effective procedure seems bound to
      replace angiography in the pretreatment evaluation of diabetic patients with
      peripheral arterial occlusive disease.

PMID- 9550899
TI  - Perioperative treatment of the diabetic patient.
AB  - The diabetic patient is frequently undergoing surgery for the underlying disease
      and its complications. Before referring the patient to surgery the diabetologist
      should carefully evaluate the presence of complications, cardiovascular, renal
      and neurologic disorders in particular. Generally no problems are posed by
      patients with NIDDM undergoing elective surgery. For more demanding patients and
      for those with IDDM the most effective and ready treatment is the continuous
      intravenous infusion of glucose, insulin and potassium. With this regimen, it is
      possible to perform major surgery in diabetics with a lower risk.

PMID- 9550900
TI  - Cardiovascular disease in diabetes and operative risk.
AB  - Among the complications of diabetes, cardiovascular disease is one of the most
      frequent, severe and invalidating. In the era before the introduction of insulin
      treatment, the most frequent cause of death in diabetes were acute metabolic and
      infectious complications; at present, after the introduction of insulin therapy
      and the consequent major change in the clinical evolution of the disease, the
      most frequent cause of death is due to cardiovascular complications. From the
      Framingham study it is possible to observe that in the adult diabetic population,
      the annual incidence of death from cardiovascular causes is about 17%, both in
      men and women, as against 8.5% in non diabetic males and 3.6% in non diabetic
      females. Major clinical forms of cardiovascular disease in diabetics are
      myocardial ischemia, autonomic neuropathy and cardiomyopathy.

PMID- 9550901
TI  - Lower limb revascularization in diabetics.
AB  - Treatment of critical lower limb ischemia in diabetics is often a complex
      clinical problem for the diabetics' general condition and the local condition of
      the territory to be revascularized. For these reasons, often the only treatment
      for diabetics with ischemic-necrotic lesions is amputation. In the symptomatology
      of arterial disease in diabetics there are three stages: claudication, rest pain,
      ulcerative-necrotic lesions and two treatment modalities: conservative treatment
      and revascularization. Conservation is based on the optimization of metabolic
      control, correction of anemia, control of risk factors, removal of necrotic
      areas, specific antibiotic treatment based on culture tests. No healing of
      ulcerative-necrotic lesions after a reasonable period of optimum therapy,
      quantified in 6 weeks, is suggestive for the presence of absolute or relative
      ischemia and diagnostic angiography is suitable for the indication for
      intravascular or surgical revascularization. The latter, in case of diabetics
      with ischemic complications of the foot, is performed in specialized centers with
      inverted saphenous veins or in situ in the supragenicular and subgenicular
      district. Recently intravascular revascularization with balloons, atherotomes,
      stents, less invasive and less traumatic than bypass revascularization, have
      become available. At present, with peripheral revascularization, limb salvage at
      5-years is feasible in 92% of diabetics with critical lower extremity ischemia.

PMID- 9550904
TI  - In search of future role models in medicine.

PMID- 9550902
TI  - The role of interventional radiology in the treatment of the diabetic foot.
AB  - Although the pathologic features of arterial disease in diabetes do not differ
      from those of simple atheromatous lesions, the plurisegmental involvement, the
      predominant subpopliteal location of lesions and the association with impaired
      cardiac and renal function in these patients imply peculiar problems in the
      selection of an adequate therapy. At present, in interventional radiology a
      number of procedures are available for intravascular therapy (angioplasty, stent,
      locoregional fibrinolisis, mechanical atherectomy), particularly suitable for
      diabetics who are affected by multisystem impairment. These procedures are not in
      opposition to the conventional ones (surgical and medical) but rather integrate
      them, allowing to extend the indications and improve the results in the treatment
      of the vasculogenic diabetic foot. Based on the personal experience the potential
      of intravascular procedures in this disease, is analyzed.

PMID- 9550903
TI  - The foot clinic. Multidisciplinary management of the patient with diabetic foot.
AB  - Treatment of a complex disease as the diabetic foot requires a multidisciplinary
      management with the close collaboration of a team for care. The most important
      members of the team are the diabetologist as coordinator, the vascular surgeon,
      the orthopedist, the radiologist, the orthopedic technician, the podiatrist and
      the nurse specialist. The care based on this arrangement should be carried out in
      dedicated rooms and times to exploit at best the organizational potential in the
      patient's interest, implemented in the foot clinic.

PMID- 9550905
TI  - Clinical pathways--a new paradigm in healthcare?

PMID- 9550906
TI  - Spontaneous corneal perforation in premature infants.
AB  - Spontaneous corneal perforation in premature infants not due to birth trauma is a
      rare event, with only 8 cases reported in the literature. We recently encountered
      a case of spontaneous corneal perforation in an extremely premature infant born
      at 26 weeks of gestation. The mechanism leading to this event was corneal
      exposure resulting in corneal epithelial defect. Clinical evidence of secondary
      infection ensued and this led to cornea thinning, descemetocoele formation and
      subsequent perforation with extrusion of intraocular contents. Although other
      mechanisms were responsible in the previously reported cases, we feel that
      exposure keratopathy leading to this complication poses a potential hazard to all
      premature infants. An awareness among care givers of this potential complication
      together with avoidance of exposure keratopathy in this group of patients is
      paramount in preventing this visually catastrophic event.

PMID- 9550907
TI  - Clinical presentation of herpes zoster in a Singapore hospital.
AB  - BACKGROUND: There is a direct correlation between increasing age and incidence of
      herpes zoster. There is an increased risk of complications in the elderly and the
      immunocompromised. OBJECTIVE: To study the clinical epidemiology of hospitalised
      patients with herpes zoster. METHODS: Medical records of all patients
      hospitalised with zoster were respectively analysed. RESULTS: Sixty-seven
      patients (3% of total admissions) were studied. There were 35 males and 32
      females with a mean age of 50.35 +/- 21.71. There was an increased proportion of
      older patients in the study cohort. Nineteen patients (28.4%) were
      immunocompromised with malignancy occurring in 9 patients. Thirteen had been on
      cytotoxic and/or steroid therapy. The commonest symptoms were rash, pain and
      fever. Eighty-five percent of the patients had complications (bacterial super
      infection in (61%), dissemination (31%), ocular involvement (5%) and post
      herpetic neuralgia (13.4%). There was an increasing frequency of duration of pain
      with increasing age in the patients with post-herpetic neuralgia. Forty-three
      patients were treated with acyclovir. The median time to healing of lesions was
      11 days. The 41 patients with bacterial super-infection received antibiotics with
      median time to healing of 12 days. CONCLUSION: Increasing age and
      immunocompromised state appear to be risk factors for developing herpes zoster in
      hospitalised patients.

PMID- 9550908
TI  - Urological injuries in gynaecological practice--when is the optimal time for
      repair?
AB  - OBJECTIVE: This is a retrospective study to determine differences in outcome and
      prognosis between patients with urological injuries treated immediately within 30
      days by definitive repair and those in whom definitive treatment was delayed.
      SUBJECTS: Patients who sustained urinary tract injuries after gynaecological
      surgery and who were subsequently referred to the Urological Department of
      (former) Toa Payoh Hospital during the period 1985-1991. RESULTS: There were nine
      injuries sustained in eight patients: six to the ureters and three to the
      bladder. One patient had a double injury: a vesico-vaginal fistula and a uretero
      vaginal fistula. There were six patients whose injuries were repaired within 30
      days of the primary gynaecological operation. They stayed an average of 10-14
      days in hospital and were discharged well. They were well both clinically and
      radiologically on follow-up. Two patients had initial drainage before definitive
      surgery was undertaken. One patient recovered fully but had to endure the
      morbidity of a prolonged, 3-month hospital stay. The other patient treated by
      simple diathermy for her vesico-vaginal fistula, never fully recovered, and
      subsequently defaulted follow-up. CONCLUSION: The old dictum of waiting 3 to 6
      months to allow oedema to subside, tissue planes to be re-established and the
      fistula to become smaller, before repair is attempted, should be reviewed.
      Recently acquired fistulae may be repaired definitively soon after diagnosis of
      the problem, with good results in competent hands, as supported in this series of
      patients studied. This shortens the length of hospital stay for the patients and
      alleviates much of the morbidity endured.

PMID- 9550909
TI  - Quality of life survey among day release patients at View Road Hospital.
AB  - OBJECTIVES: The aim of this study was to identify factors that contributed to the
      chronic patient's quality of life from both the patients' and staff's point of
      view. We were also interested in any lack of congruence between staff and patient
      perception as these could have significant implications for planning long-term
      care. METHOD: Fifty of the patients under the Day Release Scheme at View Road
      Hospital and their staff were given a modified questionnaire concerning the
      patients' quality of life. RESULTS: Generally the patients reported satisfaction
      with life domain items covering their living conditions. The majority felt safe
      in the current setting, enjoyed their work, their regular outings and parole to
      the nearby shopping centers. Significant differences were observed between the
      staff and patients' perception in life domain items relating to general well
      being, knowledge and education, relationships, in-patient care, leisure and
      vocational rehabilitation. The staff group perceived having good food, money,
      good treatment and in employment as being important to their patients' well
      being. Patients emphasised having money, family support or a partner, being
      employed, having time for recreational activities and eating good food. Having
      good health, medication and feeling at peace were also considered important by
      many of our patient. CONCLUSIONS: The findings of the study are discussed with
      regard to implications in planning rehabilitation services and improving the
      quality of care given to patients.

PMID- 9550910
TI  - The impact of the neonatal resuscitation program guidelines (NRPG) on the
      neonatal mortality in a hospital in Zhuhai, China.
AB  - AIM: The neonatal resuscitation program (NRPG) was first introduced in our
      hospital to replace the traditional resuscitation (TR) program in 1993. TR has
      been in existence in China for a long time. The implementation of NRPG was timely
      in reducing the number of infant mortality and also to disseminate to the many
      hospitals in China which are still practising TR. METHOD: A perspective study of
      4,751 newborns with 366 asphyxiated babies in a period of 2 years was carried
      out. A previous sample of 1,722 live births under the TR program was compared as
      a controlled group statistically. RESULTS: From August 1993 to August 1995, when
      NRPG was exclusively implemented in our hospital, only 16 newborns died within 7
      days, out of 4,751 births (3.4%) with 2 deaths in the delivery room. Seventeen
      newborns died within 7 days out of 1,722 births (9.9+) in the TR group, with 10
      deaths in the delivery room. From the data shown, it can be clearly seen that
      perinatal neonatal mortality rate was reduced almost 3 times after NRPG was
      implemented (chi(2) = 10.54, p < 0.01). The follow-up results of 21 cases of
      severe asphyxia at 2 months--1 year of age were normal except for one with
      cerebral palsy. CONCLUSIONS: Our study showed that NRPG was indeed a very
      effective and feasible technique during the delivery process in the reduction of
      neonatal mortality. It is important to disseminate widely the knowledge and
      technique of NRPG in places where TR is still being widely practiced especially
      in developing countries.

PMID- 9550911
TI  - An unusual case of acute onset of cardiac failure.
AB  - Rupture of the aortic sinus of Valsalva is one of the rare causes of acute
      dyspnoea. Modern advances have enabled diagnosis to be made easily with
      echocardiography as illustrated in this case. The treatment of choice is surgery
      with excellent prognosis if detected early. Therefore a high index of suspicion
      is required to diagnose this potentially threatening but yet treatable condition.

PMID- 9550912
TI  - Acute leukemia presenting as pericardial effusion--a case report.
AB  - We report a patient with acute lymphoblastic leukemia, who presented with
      pericardial effusion. There was no haematologic evidence of leukemia at the time
      of presentation. The pericardial effusion resolved with chemotherapy. Although a
      common finding at autopsy, clinically evident pericardial effusion is rare in
      leukemia. It is also extremely rare for pericardial effusion to be the presenting
      feature or to antedate haematologic evidence of leukemia. Physician awareness is
      important to make a correct diagnosis.

PMID- 9550913
TI  - Diagnostic difficulties associated with phaeochromocytoma--4 case illustrations.
AB  - The diagnosis of phaeochromocytoma can be extremely difficult with 40%-76% of
      cases escaping diagnosis during life. Until recently, the only available
      biochemical test for the detection of phaeochromocytoma in Singapore has been the
      24-hour urinary vanillyl mandelic acid (VMA). Urinary VMA has been reported to
      have a high specificity (85%-100%) but variable sensitivity (28%-90%) in the
      diagnosis of this disease. In 1993, high performance liquid chromatography (HPLC)
      assays for the measurement of urinary catecholamines and metanephrines were
      introduced at the Singapore General Hospital. Since 1993, 4 cases of
      phaeochromocytoma have been detected at our institution. We report here, the
      diverse clinical presentations of these patients. The urinary-free catecholamine
      and catecholamine metabolite levels of these patients were compared with
      corresponding levels from 12 non-phaeochromocytoma patients. Using the reference
      value of 65.6 mumol/day, we found the urinary VMA to be a highly sensitive (100%)
      test with a specificity of only 31%. In contrast, a urinary total metanephrine
      level > or = 9,000 nmol/day was both sensitive (100%) as well as specific (100%).

PMID- 9550914
TI  - Fluorescent in-situ hybridization--some of its applications in clinical
      cytogenetics.
AB  - Fluorescent in-situ hybridization (FISH) is becoming more and more relevant as an
      important future tool in prenatal and pre-implantation genetic diagnosis and
      cancer cytogenetics. This review describes the FISH technique as applied to whole
      chromosome spreads and interphase cells and discusses its applications in
      clinical cytogenetics. Information is presented on the various types of probes
      and the subsequent hybridization and detection procedures. The potential use of
      this novel FISH technique in the diagnosis of numerical and structural
      chromosomal aberrations in routine karyotyping for prenatal diagnosis, tumour
      cytogenetics and pre-implantation genetic diagnosis is outlined.

PMID- 9550915
TI  - Clinics in diagnostic imaging (31). Adrenal neuroblastoma.
AB  - A 3-year-old girl presented with epigastric pain and physical examination showed
      a hard right upper quadrant mass. Urine VMA and HVA were found to be raised. CT
      scan showed a large mass arising from the right adrenal gland, with necrotic
      areas and ring calcification There was midline extension. The diagnosis of
      neuroblastoma was confirmed by bone marrow aspiration biopsy. As the patient had
      inoperable stage IV neuroblastoma, she was treated with multi-drug chemotherapy.
      Follow-up CT scan showed excellent response to the chemotherapy, and the tumour
      was successfully resected. Harvesting of autologous peripheral bone marrow stem
      cells, megatherapy with Melphalan, and marrow rescue with the stem cells were
      effective. The child has been well for three years to date. The clinical and
      imaging features of neuroblastoma, particularly the role of imaging in staging,
      are emphasised.

PMID- 9550916
TI  - Voluntarism.

PMID- 9550917
TI  - Closed head injuries in children following the use of a sarong cradle.
AB  - INTRODUCTION: Sarong cradles are unique to South-East Asian culture. Their use
      can lead to injuries from falls, over-enthusiastic rocking and defective
      equipment. We present 19 children who attended the Accident and Emergency (A&E)
      Department of a general hospital and who sustained injuries while in a sarong
      cradle. All had closed head injuries. METHODS AND MATERIALS: The data was
      collected over a 9-month period from September 1992 to May 1993. All patients
      with a documented history of fall following the use of a sarong cradle, were
      recruited into the study. The adults accompanying the patients were interviewed
      with a structured questionnaire. The information was recorded by the doctor in
      attendance. RESULTS: The ages of the 19 patients ranged from 13 days to 29
      months. There were 17 Chinese, 1 Malay and 1 Indian. The types of closed head
      injuries included minor head injury with no external signs of injury, scalp
      lacerations, scalp haematomas and severe head injury with an extradural
      haematoma. The majority (14) were discharged from the A&E Department with head
      injury advice, 4 were admitted to the General Neurosurgical ward and one, to the
      Neurosurgical Intensive Care Unit. There were no fatalities in this group. The
      accidents happened while the children were either sleeping (14), playing (4) or
      feeding (1). CONCLUSIONS: While most head injuries sustained in this manner are
      usually mild, there is a potential that such injuries may lead to more serious
      injuries. Care givers who use the sarong cradle should be aware of the dangers
      and exercise due care during use.

PMID- 9550918
TI  - A 5-year review of FIGO stage IB cervical cancer in an Asian population.
AB  - OBJECTIVE: We studied the clinical patterns and outcome of patients with FIGO
      (1985) Stage 1b cervical cancer. In particular, looking at the clinico
      pathological characteristics in relation with disease recurrence. PATIENTS &
      METHODS: Ninety-nine Asian patients were managed at (the former) K K Hospital,
      Singapore, from 1987 to 1991. The mean and median follow-up periods were 67 and
      60 months respectively. This study was performed in 1995. RESULTS: The majority
      of the patients (81%) was treated by radical hysterectomy with or without
      adjuvant radiotherapy/chemotherapy while 15% were treated by radical pelvic
      radiotherapy alone and 4% of patients had pelvic radiotherapy following the
      diagnosis of cervical cancer after a simple hysterectomy. Thirteen patients
      developed tumour recurrence (13.1%). In these patients, there was a greater
      proportion of adenocarcinomas (31% vs 13%, p = 0.1065), lymph node metastases
      (45% vs 20%, p = 0.09) and surgical margins involvement (45% vs 7%) 7%, p =
      0.004) while there seemed to be no difference in histological sub-types, vascular
      space involvement and cytological grading. The relative risks of developing
      tumour recurrence in patients with adenocarcinoma was 2.5 times (95% CI: 0.88
      7.05), lymph-node metastasis: 2.3 times (95% CI: 0.96-4.93) and involved surgical
      margins; 5.9 times (95% CI: 2.27-15.5). The mean time to recurrence were 21.7
      months with all of them detected within 36 months following primary therapy. All
      of them had abnormal physical findings while routine follow-up Pap smear was
      positive in only one patient (8%). In general, the outcome of salvage treatment
      was poor. CONCLUSIONS: In our group of patients with FIGO Stage lb cervix cancer,
      majority had radical surgery performed initially. Thirteen percent had disease
      recurrence, in which there were greater proportions of patients with
      adenocarcinoma, lymph-node metastasis, and involved surgical margins. The mean
      time-to-recurrence was 21.7 months with all detected by 36 months. Routine follow
      up Pap smear seemed to be a poor indicator of disease status.

PMID- 9550919
TI  - Efficacy of intravenous adenosine in treatment of paroxysmal supraventricular
      tachycardia in the local population.
AB  - In a prospective study conducted over 4 months at the Accident and Emergency
      Department, 21 patients with 24 episodes of spontaneous paroxysmal
      supraventricular tachycardia (PSVT) were treated with intravenous adenosine at
      incremental doses of 3 mg, 6 mg, 9 mg and 12 mg until termination of the PSVT.
      There were 6 males and 15 females. The mean age was 54 +/- 17 years (range from
      23 to 83 years). The mean QRS rate was 171 +/- 21 per minute. When data were
      expressed in a cumulative manner, the response to intravenous adenosine 3 mg, 6
      mg, 9 mg and 12 mg in the 24 episodes of PSVT were 5 episodes (21%), 16 episodes
      (67%), 20 episodes (83%) and 20 episodes (83%) respectively. Adverse effects were
      present in 10 episodes (42%) of the PSVT. They were all mild and transient,
      lasting less than 1 minute.

PMID- 9550920
TI  - Anterior cruciate ligament reconstruction using patellar tendon autografts--a
      review of results.
AB  - AIM: The aim of this retrospective study was to review the results of anterior
      cruciate ligament reconstruction using patellar tendon autografts. METHODS: Forty
      one knees were available for evaluation at a minimum of 24 months follow-up.
      Objective, subjective, functional and KT-1000 arthrometric tests were performed.
      RESULTS: 92.7% had a negative or trace pivot shift at follow-up. None of the
      patients had rupture of the autografts at review. The mean post-operative single
      legged hop was 81%. The KT-1000 arthrometric evaluation post-operatively revealed
      a mean maximum manual difference of 0.5 mm; 90.2% of these patients had a maximum
      manual difference of less than 4 mm. Five patients (12.2%) had a "tighter"
      reconstructed knee (a negative mean maximum manual difference). More than 70% of
      the patients in this series had good to excellent results on functional,
      subjective and objective evaluation scores. CONCLUSION: Excellent motion
      recovery, reliable stabilisation rates, good arthrometric results and encouraging
      post-operative functional, subjective and objective evaluation scores can be
      expected in patients undergoing anterior cruciate ligament reconstruction with
      patellar tendon autografts.

PMID- 9550921
TI  - Clinics in diagnostic imaging (32). Opportunistic pneumonia in acquired
      immunodeficiency syndrome (AIDS)
AB  - A 24-year old HIV-positive patient presented with fever and productive cough.
      Chest radiograph showed a cavitating pulmonary infiltrate. Diagnosis of
      Nocardosis was made from modified acid-fast stain of his sputum specimen. He
      responded well to antibiotics. The radiographic patterns of opportunistic
      infection in patients with AIDS, with emphasis on cavitary pneumonia, is
      discussed.

PMID- 9550923
TI  - Connection between the medical profession and the pharmaceutical industry.

PMID- 9550922
TI  - The Marei Ika Daigaku (Syonan Medical College) during the Japanese occupation of
      Singapore (1942-1945).
AB  - During the Japanese Occupation of Singapore (1942-1945), Singapore was renamed
      Syonan (or Syonanto). The Japanese Military Administration established The
      Medical College on 27 April 2603 (1943) and it was known as The Marei Ika Daigaku
      or Syonan Medical College. It was sited at the Tan Tock Seng Hospital (Hakua
      Byoin). The Ika Daigaku relocated to the General Hospital, Malacca in February
      2604 (1944) where it functioned till the end of the Japanese Occupation in
      September 1945. About 200 students from Singapore, Malaya, Sumatra and Java
      attended the Syonan Medical College; the students were taught mainly Japanese
      language and culture.

PMID- 9550924
TI  - The elusive goal of transfusion safety.

PMID- 9550925
TI  - Abnormal spinal fluid in hypertensive encephalopathy.
AB  - A 44-year-old white male presented with marked hypertension and encephalopathy.
      His spinal fluid showed a neutrophilic pleocytosis in the absence of infection.
      While cases of hypertensive encephalopathy with concomitant minor lymphocytic
      pleocytosis have been occasionally described, it is distinctly abnormal to have a
      neutrophilic pleocytosis in this setting.

PMID- 9550926
TI  - Ibuprofen use in pediatric patients.

PMID- 9550927
TI  - Canalith repositioning procedure for relief of post-stapedectomy benign
      paroxysmal positional vertigo.
AB  - A 41-year-old woman underwent a successful stapedectomy for relief of conductive
      hearing loss due to otosclerosis. Post-operatively, she developed persistent
      symptoms of benign paroxysmal positional vertigo (BPPV). Eight weeks later, a
      canalith repositioning procedure was performed in the office, with immediate
      complete resolution of her vertigo. Anatomic and pathophysiologic implications of
      these observations will be discussed.

PMID- 9550928
TI  - A comparative longitudinal study of gastrostomy devices in children.
AB  - Long-term gastrostomy is a predictable intervention to ameliorate the effects of
      feeding and swallowing difficulties among children with severe spastic cerebral
      palsy. The evidence evaluating the efficacy and implications of the available
      gastrostomy devices in common use has focused primarily on the operative phase,
      ignoring the long-term effects that may be critical from a nurse's or family
      caregiver's point of view. In this study, the authors describe a sample of
      children with gastrostomy, comparing skin-level and tube devices on measures of
      nutritional outcome, complications, and caregiver satisfaction. In contrast to
      manufacturer's claims about the superiority of skin-level devices, the results
      presented here reveal few differences between the devices. The authors conclude,
      therefore, that device selection should be determined by individualized
      comprehensive assessment of the child and family circumstances.

PMID- 9550929
TI  - The evaluation of motivation for sexual health among women.
AB  - This study conducted a psychometric evaluation of the construct validity of the
      Health Self-Determinism Index-Sexual (HSDI-S). The instrument was modified to
      measure motivation related to sexual health rather than motivation of general
      health in the Health Self-Determinism Index (HSDI). The HSDI-S was completed by
      260 conveniently selected women (between the ages of 18 and 44) attending primary
      care clinics in the southeastern United States. Confirmatory factor analysis
      using LISREL did not validate the four subscales of the original HSDI. Subsequent
      exploratory and confirmatory factor analysis isolated a single-factor model
      composed of eight items: four judgment items and four external/internal cues
      items. This finding is suggestive that changes in wording appear to have shifted
      the responses from motivation for sexual health to that of women's perception of
      their role in intimate relationships. The eight extrinsically worded items
      isolate a single-factor model of social and cultural influences of child-bearing
      age women's intimate relationships.

PMID- 9550930
TI  - Establishing the nurse-family relationship in the intensive care unit.
AB  - The nurse-family relationship in the intensive care unit (ICU) may replace the
      traditional nurse-patient relationship due to the patient's compromised state. As
      a result, the nurse-family relationship becomes extremely important. Nurses and
      families may develop a relationship in which they work together to benefit the
      patient, or an inadequate relationship may develop. In this study, strategies
      used by nurses and families to either develop or inhibit the development of the
      nurse-family relationship were identified. Using unstructured interviews with ICU
      nurses and family members of ICU patients, categories of strategies were
      identified and behaviors described. Nurses and families perceived that they each
      displayed only positive behaviors yet identified inhibiting behaviors of the
      other. Once the behaviors were shown to nurses as secondary informants, they were
      able to identify with their negative behaviors. An understanding of these
      strategies will help nurses to reevaluate their practice and enhance their
      understanding of the behaviors of family members.

PMID- 9550931
TI  - Hopefulness, self-esteem, and perceived social support among pregnant and
      nonpregnant adolescents.
AB  - The concepts of hope, self-esteem, and social support have been identified as
      important factors in understanding a wide range of adolescent behaviors. The
      purpose of this exploratory study was to examine the relationship of perceived
      hopefulness, self-esteem, and social support with pregnancy status. Employing a
      cross-sectional design, a sample of pregnant (n = 58) and nonpregnant (n = 91)
      adolescents between the ages of 14 and 18 completed the Hopefulness Scale for
      Adolescents (HSA), the Rosenberg Self-Esteem Scale (RSES), and the Norbeck Social
      Support Questionnaire (NSSQ). Multiple regression analyses were used to assess
      the association of pregnancy status with hopefulness, self-esteem, and social
      support while controlling for age and socioeconomic status (SES). The effects of
      pregnancy status on each psychosocial variable were examined independently.
      Findings revealed pregnancy status was not associated with hopefulness, self
      esteem, or perceived social support when age and SES were controlled.

PMID- 9550932
TI  - Experiences of African American adolescent fathers.
AB  - Social and cultural factors influence the experience of fatherhood. This
      descriptive focus-group study describes the lived experience of fatherhood from
      the perspectives of 5 unmarried, low-income, African American adolescent fathers
      in a Midwestern urban area. Naturalistic inquiry approach guided the study. Seven
      themes of fatherhood emerged: barriers to fatherhood, value of fatherhood,
      introduction to fatherhood, competencies of fatherhood, role-set relationships,
      social norms of fatherhood, and father-child contact. This study suggests that
      nurses should support the involvement of adolescent fathers with their children.
      Future study may determine the influence of adult female family members on the
      decisions of adolescent fathers to remain involved with their children.

PMID- 9550934
TI  - Learning how to do research.

PMID- 9550933
TI  - Measuring organizational readiness for nursing research programs.
AB  - Nursing research programs are important innovations for health services
      organizations (HSOs). Evidence supports the positive impact that successful
      programs have on both clinical practice and patient outcomes. In the current era
      of scarce health care resources, decision makers must be able to accurately judge
      HSO readiness for nursing research programs to facilitate their success. Judging
      innovation readiness is an important and complex process for decision makers. An
      Innovation Readiness Scale (IRS) was developed from research-based HSO contextual
      cues identified by nurse researchers as supportive of successful hospital-based
      nursing research programs. The IRS provides decision makers with a measure by
      which to judge HSO readiness for nursing research programs. Psychometric results
      are reported from a pilot and actual test of the IRS in two urban acute care
      settings involved in nursing research program innovation.

PMID- 9550935
TI  - Strategies for conducting intervention research in schools.

PMID- 9550936
TI  - Computerized data collection: example of a time-motion study.

PMID- 9550937
TI  - Research risks with diverse groups: issues and safeguards.

PMID- 9550938
TI  - Adenosine and ATP: progress in their receptors' structures and functions.

PMID- 9550939
TI  - New delta-opioid antagonists as pharmacological probes.

PMID- 9550940
TI  - Striatal adenosine A2A receptors--where are they? What do they do?

PMID- 9550941
TI  - Revisiting the effect compartment through timing errors in drug administration.
AB  - The variations in the pharmacological effects induced by timing errors in drug
      intake are compared for two drugs, one acting by way of an effect compartment and
      the other directly from the central compartment. A simulation was performed for
      two drugs having the same concentration-effect relationship at the receptor site,
      the same mean effect at equilibrium and identical concentrations in the central
      compartment. In this article. Patrice Nony, Michel Cucherat and Jean-Pierre
      Boissel discuss how, for the same variability of concentrations in the central
      compartment, the variations in mean effects are different. When there is a large
      variability in the interval separating two consecutive doses, the model that
      includes an effect compartment dampens the pharmacokinetic variability present in
      the central compartment. Such an approach may be useful for the prescription
      recommendations of drugs, especially those with narrow therapeutic indices.

PMID- 9550942
TI  - Endocannabinoids: a new class of vasoactive substances.
AB  - Endogenous cannabinoids (endocannabinoids) have recently been identified in the
      CNS and attention has now turned to their cardiovascular actions. The prototypic
      endocannabinoid, anandamide, derived from arachidonic acid, has been shown to be
      a vasorelaxant, particularly in the resistance vasculature. This vasorelaxation
      has been shown to be both endothelium-independent and -dependent, depending on
      the vascular bed. It has been proposed that an endocannabinoid may mediate the
      nitric oxide- and prostanoid-independent component of endothelium-dependent
      relaxations, as these responses are sensitive to a cannabinoid receptor
      antagonist and show similarities to anandamide-induced relaxations. This
      hypothesis has generated much controversy and the emerging conflicts in the
      literature are discussed in this article by Michael Randall and David Kendall.
      Despite this controversy, it has recently been shown that anandamide is produced
      by endothelial cells. Clearly, much work is required to adequately define the
      physiological significance of endocannabinoids in the cardiovascular system.

PMID- 9550943
TI  - To what extent have functional studies of ischaemia in animals been useful in the
      assessment of potential neuroprotective agents?
AB  - A general consensus is being reached on the use of a combination of mortality and
      functional end-points in clinical trials of neuroprotective agents. However, to
      date, few preclinical studies have examined the effects of putative
      neuroprotective agents on functional outcome after ischaemia. The data described
      in this review show the importance of combining both histopathological and
      neurobehavioural studies when evaluating the neuroprotective efficacy of anti
      ischaemic agents in animal models of cerebral ischaemia. Here, Jackie Hunter, Ken
      Mackay and Derek Rogers argue that measures of functional improvement in models
      of ischaemia should be incorporated to characterize further the neuroprotection
      afforded by a compound that could aid the selection of doses and end-point
      measures in early clinical trials.

PMID- 9550946
TI  - Improving the health of NHS workers.

PMID- 9550944
TI  - The role of stress in drug self-administration.
AB  - Environmental experiences have an important effect on the sensitivity of an
      individual to drugs of abuse. Studies of drug self-administration in laboratory
      animals have shown that both physical and psychological stressors facilitate the
      acquisition of drug self-administration, probably by increasing the reinforcing
      efficacy of drugs of abuse. Stressors also facilitate the reinstatement of drug
      taking even after prolonged periods of withdrawal. The adrenal hormones,
      glucocorticoids, which increase the sensitivity of mesencephalic dopaminergic
      neurones to drugs, seem to be one of the biological substrates of the effects of
      stress on the propensity to develop drug intake. In this review, Pier Vincenzo
      Piazza and Michel Le Moal discuss theories of drug abuse, the influence of
      different stressful experiences on drug self-administration and their possible
      mechanisms of action.

PMID- 9550945
TI  - Informed consent: edging forwards (and backwards)

PMID- 9550947
TI  - Chernobyl and public health.

PMID- 9550948
TI  - Inflammatory responses and coronary heart disease.

PMID- 9550949
TI  - Consultant suspended for not getting consent for cardiac procedure.

PMID- 9550950
TI  - Labour talks tough on waiting lists.

PMID- 9550951
TI  - WHO identifies 16 countries struggling to control tuberculosis.

PMID- 9550952
TI  - The children's advocate. Interview by Kamran Abbasi.

PMID- 9550953
TI  - Fluid resuscitation with colloid or crystalloid solutions in critically ill
      patients: a systematic review of randomised trials.
AB  - OBJECTIVE: To determine the effect on mortality of rescuscitation with colloid
      solutions compared with resuscitation with crystalloids. DESIGN: Systematic
      review of randomised controlled trials of resuscitation with colloids compared
      with crystalloids for volume replacement of critically ill patients; analysis
      stratified according to patient type and quality of allocation concealment.
      SUBJECTS: 37 randomised controlled trials were eligible, of which 26 unconfounded
      trials compared colloids with crystalloids (n = 1622). (The 10 trials that
      compared colloid in hypertonic crystalloid with isotonic crystalloid (n = 1422)
      and one trial that compared colloid in isotonic crystalloid with hypertonic
      crystalloid (n = 38) are described in the longer version on our website
      www.bmj.com). MAIN OUTCOME MEASURES: Mortality from all causes at end of follow
      up for each trial. RESULTS: Resuscitation with colloids was associated with an
      increased absolute risk of mortality of 4% (95% confidence interval 0% to 8%), or
      four extra deaths for every 100 patients resuscitated. The summary effect measure
      shifted towards increased mortality with colloids when only trials with adequate
      concealment of allocation were included. There was no evidence for differences in
      effect among patients with different types of injury that required fluid
      resuscitation. CONCLUSIONS: This systematic review does not support the continued
      use of colloids for volume replacement in critically ill patients.

PMID- 9550954
TI  - Is day care equivalent to inpatient care for active rheumatoid arthritis?
      Randomised controlled clinical and economic evaluation.
AB  - OBJECTIVE: To test the clinical equivalence and resource consequences of day care
      with inpatient care for active rheumatoid arthritis. DESIGN: Randomised
      controlled clinical trial with integrated cost minimisation economic evaluation.
      SETTING: Rheumatic diseases unit at a teaching hospital between 1994 and 1996.
      SUBJECTS: 118 consecutive patients with active rheumatoid arthritis randomised to
      receive either day care or inpatient care. MAIN OUTCOME MEASURES: Clinical
      assessments recorded on admission, discharge, and follow up at 12 months
      comprised: the health assessment questionnaire, Ritchie articular index,
      erythrocyte sedimentation rate, hospital anxiety and depression scale, and
      Steinbrocker functional class. Resource estimates were of the direct and indirect
      costs relating to treatment for rheumatoid arthritis. Secondary outcome measures
      (health utility) were ascertained by time trade off and with the quality of well
      being scale. RESULTS: Both groups had improvement in scores on the health
      assessment questionnaire and Ritchie index and erythrocyte sedimentation rate
      after hospital treatment (P < 0.0001) but clinical outcome did not differ
      significantly between the groups either at discharge or follow up. The mean
      hospital cost per patient for day care, 798 Pounds (95% confidence interval 705
      Pounds to 888 Pounds), was lower than for inpatient care, 1253 Pounds (1155
      Pounds to 1370 Pounds), but this difference was offset by higher community,
      travel, and readmission costs. The difference in total cost per patient between
      day care and inpatient care was small (1789 Pounds (1539 Pounds to 2027 Pounds) v
      2021 Pounds (1834 Pounds to 2230 Pounds)). Quantile regression analysis showed a
      cost difference in favour of day care up to the 50th centile (374 Pounds; 639
      Pounds to 109 Pounds). CONCLUSIONS: Day care and inpatient care for patients with
      uncomplicated active rheumatoid arthritis have equivalent clinical outcome with a
      small difference in overall resource cost in favour of day care. The choice of
      management strategy may depend increasingly on convenience, satisfaction, or more
      comprehensive health measures reflecting the preferences of patients, providers,
      and service commissioners.

PMID- 9550955
TI  - Benefit of heparin in peripheral venous and arterial catheters: systematic review
      and meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To evaluate the effect of heparin on duration of catheter patency and
      on prevention of complications associated with use of peripheral venous and
      arterial catheters. DESIGN: Critical appraisal and meta-analysis of 26 randomised
      controlled trials that evaluated infusion of heparin intermittently or
      continuously. Thirteen trials of peripheral venous catheters and two of
      peripheral arterial catheters met criteria for inclusion. MAIN OUTCOME MEASURES:
      Data on the populations, interventions, outcomes, and methodological quality.
      RESULTS: For peripheral venous catheters locked between use flushing with 10 U/ml
      of heparin instead of normal saline did not reduce the incidence of catheter
      clotting and phlebitis or improve catheter patency. When heparin was given as a
      continuous infusion at 1 U/ml the risk of phlebitis decreased (relative risk
      0.55; 95% confidence interval 0.39 to 0.77), the duration of patency increased,
      and infusion failure was reduced (0.88; 0.72 to 1.07). Heparin significantly
      prolonged duration of patency of radial artery catheters and decreased the risk
      of clot formation (0.51; 0.42 to 0.61). CONCLUSIONS: Use of intermittent heparin
      flushes at doses of 10 U/ml in peripheral venous catheters locked between use had
      no benefit over normal saline flush. Infusion of low dose heparin through a
      peripheral arterial catheter prolonged the duration of patency but further study
      is needed to establish its benefit for peripheral venous catheters.

PMID- 9550956
TI  - Use of anticonvulsants in eclampsia and pre-eclampsia: survey of obstetricians in
      the United Kingdom and Republic of Ireland.

PMID- 9550957
TI  - Satisfaction with clinical nurse specialists in a breast care clinic:
      questionnaire survey.

PMID- 9550958
TI  - Health beliefs and folk models of diabetes in British Bangladeshis: a qualitative
      study.
AB  - OBJECTIVE: To explore the experience of diabetes in British Bangladeshis, since
      successful management of diabetes requires attention not just to observable
      behaviour but to the underlying attitudes and belief systems which drive that
      behaviour. DESIGN: Qualitative study of subjects' experience of diabetes using
      narratives, semi-structured interviews, focus groups, and pile sorting exercises.
      A new qualitative method, the structured vignette, was developed for validating
      researchers' understanding of primary level culture. SUBJECTS: 40 British
      Bangladeshi patients with diabetes, and 10 non-Bangladeshi controls, recruited
      from primary care. RESULT: Several constructs were detected in relation to body
      image, cause and nature of diabetes, food classification, and knowledge of
      complications. In some areas, the similarities between Bangladeshi and non
      Bangladeshi subjects were as striking as their differences. There was little
      evidence of a fatalistic or deterministic attitude to prognosis, and most
      informants seemed highly motivated to alter their diet and comply with treatment.
      Structural and material barriers to behaviour change were at least as important
      as "cultural" ones. CONCLUSION: Bangladeshi culture is neither seamless nor
      static, but some widely held beliefs and behaviours have been identified. Some of
      these have a potentially beneficial effect on health and should be used as the
      starting point for culturally sensitive diabetes education.

PMID- 9550959
TI  - Using epidemiological data to guide clinical practice: review of studies on
      cardiovascular disease and use of combined oral contraceptives.
AB  - OBJECTIVE: To explore the usefulness of epidemiological data to guide clinical
      practice by seeking an answer to the question "What is the risk of cardiovascular
      disease among users of currently available, low dose, combined oral
      contraceptives who are aged less than 35 years, do not smoke, and do not have a
      medical condition known to increase the risk of vascular disease?" DESIGN: Review
      of all relevant published studies identified from the library of references held
      by Royal College of General Practitioners' Manchester Research Unit, checking of
      reference lists of identified studies, and Medline search. MAIN OUTCOME MEASURES:
      Identification of methodologically sound studies able to address the specific
      clinical question. RESULTS: Our literature search identified 74 papers about the
      relation between current use of combined oral contraceptives and cardiovascular
      disease: 23 papers reporting risk of venous thromboembolism, 22 on ischaemic
      stroke, 13 on haemorrhagic stroke or subarachnoid haemorrhage, 13 on all stroke,
      and 33 on myocardial infarction. Only five papers provided information that
      directly addressed our clinical question; all related to the risk of venous
      thromboembolism. Fourteen of the discarded papers probably had the potential to
      answer our clinical question. CONCLUSIONS: Much of the epidemiological data about
      the risk of cardiovascular disease in users of combined oral contraceptives is
      not useful to clinicians. Some of the discarded data could be made more useful to
      clinicians by reanalysis. This situation is unlikely to be unique to use of
      contraceptives.

PMID- 9550960
TI  - Transferring medical images on the World Wide Web for emergency clinical
      management: a case report.

PMID- 9550961
TI  - When can odds ratios mislead?

PMID- 9550962
TI  - Periodontitis for medical practitioners.

PMID- 9550963
TI  - ABC of allergies. Asthma and allergy.

PMID- 9550964
TI  - Informed consent in medical research.

PMID- 9550965
TI  - Thrombolytic treatment for acute ischaemic stroke: consent can be ethical.

PMID- 9550968
TI  - Separation and other problems that threaten relationships.

PMID- 9550966
TI  - Informed consent and research.

PMID- 9550967
TI  - Videos, photographs, and patient consent.

PMID- 9550969
TI  - Economic evaluation: an introduction.

PMID- 9550970
TI  - Clinical management of meningococcal disease. Lumbar puncture is still performed
      in patients with contraindications.

PMID- 9550971
TI  - Clinical management of meningococcal disease. Coning may occur without lumbar
      puncture being done.

PMID- 9550972
TI  - Clinical management of meningococcal disease. Laboratory confirmation is
      important.

PMID- 9550973
TI  - Clinical management of meningococcal disease. Prospective international
      registration of patients may be needed.

PMID- 9550975
TI  - Blood products produced from plasma from donors in UK are still being made.

PMID- 9550974
TI  - Meta-analysis of cigarette smoking, bone mineral density, and risk of hip
      fracture. Three studies were omitted from meta-analysis.

PMID- 9550976
TI  - Lumbar puncture and headache. Obtaining fluid samples and measuring intrathecal
      pressure may require different approaches.

PMID- 9550977
TI  - Lumbar puncture and headache. Replacing the stylet before withdrawing the needle
      may help to prevent headache.

PMID- 9550978
TI  - Lumbar puncture and headache. "Atraumatic needle" is a better term than "blunt
      needle".

PMID- 9550979
TI  - Lumbar puncture and headache. Aspirating cerebrospinal fluid speeds up procedure.

PMID- 9550980
TI  - Lumbar puncture and headache. Epidural blood patching can be used to treat
      headache.

PMID- 9550981
TI  - Smoking, alcohol and coffee consumption, and H pylori infection. Alcohol
      consumption eliminates rather than prevents infection with H pylori.

PMID- 9550982
TI  - Smoking, alcohol and coffee consumption, and H pylori infection. Cross sectional
      study shows no protective effect of alcohol.

PMID- 9550983
TI  - UN Declaration of Human Rights. NHS does not heed human rights declaration.

PMID- 9550984
TI  - UN Declaration of Human Rights. Medical students need to learn humanitarian
      values.

PMID- 9550985
TI  - Medical Devices Agency wants to see prospective clinical study of contraceptive
      device.

PMID- 9550986
TI  - Patients offered treatment for CHD need full information to make decision.

PMID- 9550987
TI  - Decline in cognitive function in Parkinson's disease may be due to dementia with
      Lewy bodies.

PMID- 9550988
TI  - Publication of pictures of patient on BMJ's website was mistake.

PMID- 9550989
TI  - The prevention of perinatal HIV transmission in the less-developed world.

PMID- 9550990
TI  - HIV research, ethics, and the developing world.

PMID- 9550991
TI  - Trade-offs in prenatal detection of Down syndrome.
AB  - OBJECTIVES: This paper presents the results of different screening policies for
      prenatal detection of Down syndrome that would allow decision makers to make
      informed choices. METHODS: A decision analysis model was built to compare 8
      screening policies with regard to a selected set of outcome measures.
      Probabilities used in the analysis were obtained from official administrative
      data reports in Spain and Catalonia and from data published in the medical
      literature. Sensitivity analyses were carried out to test the robustness of
      screening policies' results to changes in uptake rates, diagnostic accuracy, and
      resources consumed. RESULTS: Selected screening policies posed major trades-offs
      regarding detection rates, false-positive results, fetal loss, and costs of the
      programs. All outcome measures considered were found quite robust to changes in
      uptake rates. Sensitivity and specificity rates of screening tests were shown to
      be the most influential factors in the outcome measures considered. CONCLUSIONS:
      The disclosed trade-offs emphasize the need to comprehensively inform decision
      makers about both positive and negative consequences of adopting one screening
      policy or another.

PMID- 9550992
TI  - Rational Down syndrome screening policy.

PMID- 9550993
TI  - Human rights and maternal-fetal HIV transmission prevention trials in Africa.
AB  - The human rights issues raised by the conduct of maternal-fetal human
      immunodeficiency virus transmission trials in Africa are not unique to either
      acquired immunodeficiency syndrome or Africa, but public discussion of these
      trials presents an opportunity for the United States and other wealthy nations to
      take the rights and welfare of impoverished populations seriously. The central
      issue at stake when developed countries perform research on subjects in
      developing countries is exploitation. The only way to prevent exploitation of a
      research population is to insist not only that informed consent be obtained but
      also that, should an intervention be proven beneficial, the intervention will be
      delivered to the impoverished population. Human rights are universal and cannot
      be compromised solely on the basis of beliefs or practices of any one country or
      group. The challenge to the developed countries is to implement programs to
      improve the health of the people in developing countries both by improving public
      health infrastructure and by delivering effective drugs and vaccines to the
      people.

PMID- 9550994
TI  - Placebo controls in HIV perinatal transmission trials: a South African's
      viewpoint.

PMID- 9550995
TI  - The debate over maternal-fetal HIV transmission prevention trials in Africa,
      Asia, and the Caribbean: racist exploitation or exploitation of racism?

PMID- 9550996
TI  - Ethical challenges in efficacy trials of vaginal microbicides for HIV prevention.
AB  - This paper discusses some of the ethical challenges raised by advanced clinical
      trials designed to assess the safety and efficacy of vaginal microbicides in
      protecting women from HIV infection. The ethical principles that guide clinical
      research involving human subjects require that all participants in such trials be
      provided available measures known to reduce the risk of HIV infection. However,
      this will reduce the ability of the study to assess the protective effect of the
      test microbicide. In addition, providing extensive services to trial participants
      may be construed as an undue inducement if the study is being conducted among
      vulnerable groups such as sex workers or women from disadvantaged communities.
      Suggestions are provided to resolve this dilemma in the planning and
      implementation of HIV prevention services for trial participants.

PMID- 9550997
TI  - Deficient dietary iron intakes among women and children in Russia: evidence from
      the Russian Longitudinal Monitoring Survey.
AB  - OBJECTIVES: This study evaluated the iron sufficiency of the Russian diet.
      METHODS: Data were obtained from 24-hour dietary recalls conducted in 4 rounds
      (1992 through 1994) of a nationally representative longitudinal survey of 10,548
      women and children. Iron bioavailability was estimated via algorithms adjusting
      for enhancers (heme, vitamin C) and inhibitors (tannins in tea, phytates in
      grains) consumed at the same meal. RESULTS: Dietary iron intakes were deficient
      in the most vulnerable groups: young children and women of reproductive age.
      Poverty status was strongly associated with deficiency. After adjustment for
      enhancers and inhibitors, estimated bioavailable iron intakes at 3% to 4% of
      total iron were inadequate in all women and children. CONCLUSIONS: These dietary
      data suggest that Russian women and children are at high risk of iron deficiency.
      Grain products rich in phytates, which inhibit absorption, were the major food
      source of iron in Russia. High intakes of tea and low consumption of vitamin C
      also inhibited iron bioavailability. Since changes in eating behavior could
      potentially double iron bioavailability, educational programs should be explored
      as a strategy for improving iron nutriture.

PMID- 9550998
TI  - Substance use among nurses: differences between specialties.
AB  - OBJECTIVES: Valid data on factors that increase a health care worker's likelihood
      of substance use are integral in ensuring professional standards and quality
      health care for consumers. This study explored the association between nursing
      specialty and past-year substance use. METHODS: In an anonymous mailed survey, a
      balanced stratified sample of registered nurses (n = 4438) reported their use of
      marijuana, cocaine, and prescription-type drugs, as well as cigarette smoking and
      binge drinking. RESULTS: Prevalence of use of all substances was 32%. Rates
      varied by specialty, even when sociodemographics were controlled. Compared with
      nurses in women's health, pediatrics, and general practice, emergency nurses were
      3.5 times as likely to use marijuana or cocaine (odds ratio [OR] = 3.5; 95%
      confidence interval [CI] = 1.5, 8.2); oncology and administration nurses were
      twice as likely to engage in binge drinking; and psychiatric nurses were most
      likely to smoke (OR = 2.4; 95% CI = 1.6, 3.8). No specialty differences appeared
      for prescription-type drug use. CONCLUSIONS: Certain nursing specialties were
      more likely than others to be associated with substance use. The differences were
      not explained by demographic characteristics. Inasmuch as a comparison of these
      results for nurses with prior work on physicians found considerable agreement by
      specialty, preventive initiatives should consider inter-disciplinary approaches
      to substance use education.

PMID- 9550999
TI  - Unemployment and the likelihood of detecting early-stage breast cancer.
AB  - OBJECTIVES: The objective of this study was to test the hypothesis that
      unexpectedly high unemployment in a community is associated with reduced odds
      that registered breast tumors are local. METHODS: The hypothesis was tested with
      data from San Francisco for the 132 months beginning with January 1983. RESULTS:
      Registered breast tumors were less likely to be local during periods of
      unexpectedly high unemployment (8% less likely among non-Hispanic White women and
      24% less likely among African-American women). CONCLUSIONS: Job loss may restrict
      access to health services. Fear of job loss may also distract women from breast
      self-examination and the identification of suspicious breast signs.

PMID- 9551000
TI  - The protective effect of condoms and nonoxynol-9 against HIV infection.
AB  - OBJECTIVES: Whether or not spermicides can reduce the risk of human
      immunodeficiency virus (HIV) transmission remains an important question for the
      control of heterosexual HIV transmission. The authors provide estimates from a
      reanalysis of one of the few observational studies on the efficacy of condoms and
      spermicides, used separately and together, per vaginal contact. METHODS: In this
      reanalysis, three different models were used to assess the efficacy of
      spermicides and condoms: linear (Pearl index), exponential (maximum likelihood),
      and monotonic (marginal likelihood). RESULTS: Reported use of barrier methods
      among 27,432 contacts was as follows: condoms plus nonoxynol-9, 39%; condoms
      alone, 25%; nonoxynol-9 alone, 24%; and unprotected, 11%. Under all three models,
      the results indicate a strong protective effect for spermicidal suppositories.
      The Pearl index indicated that spermicide alone is apparently efficacious, but
      the efficacy per contact cannot be quantified with this approach. Maximum
      likelihood estimates for the efficacy of nonoxynol-9 alone and condoms (with or
      without nonoxynol-9) were 100% (95% confidence interval [CI95] = 43%, 100%) and
      92% (95% CI95 = 79%, 100%), respectively. CONCLUSIONS: The data from this
      observational study suggest that spermicides may be efficacious in reducing the
      risk of HIV transmission.

PMID- 9551001
TI  - Risk factors for congenital syphilis in infants of women with syphilis in South
      Carolina.
AB  - OBJECTIVES: This study examined risk factors for congenital syphilis in South
      Carolina. METHODS: Case infants with presumptive and confirmed congenital
      syphilis were compared with control infants born to women with reactive
      serologies during pregnancy, allowing investigation of risk factors for
      congenital rather than acquired transmission of syphilis. Data were collected
      from congenital syphilis report forms and birth certificates for 186 case infants
      and 487 controls born from 1991 to 1993. Odds ratios were calculated for maternal
      risk factors. RESULTS: Significant statistical trends were found for timing of
      first prenatal visit and number of visits. Other significant factors included
      rural residence (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.4, 2.9)
      and previous pregnancy loss (OR = 0.3, 95% CI = 0.2, 0.6). CONCLUSIONS:
      Prevention of congenital syphilis may be less effective among pregnant women with
      syphilis in South Carolina who have fewer prenatal care visits. Health care
      providers need further education on maternal/child syphilis management and
      techniques for motivating and educating patients.

PMID- 9551002
TI  - Changing fruit and vegetable consumption among children: the 5-a-Day Power Plus
      program in St. Paul, Minnesota.
AB  - OBJECTIVES: A randomized school based trial sought to increase fruit and
      vegetable consumption among children using a multicomponent approach. METHODS:
      The intervention, conducted in 20 elementary schools in St. Paul, targeted a
      multiethnic group of children who were in the fourth grade in spring 1995 and the
      fifth grade in fall 1995. The intervention consisted of behavioral curricula in
      classrooms, parental involvement, school food service changes, and industry
      support and involvement. Lunchroom observations and 24-hour food recalls measured
      food consumption. Parent telephone surveys and a health behavior questionnaire
      measured psychosocial factors. RESULTS: The intervention increased lunchtime
      fruit consumption and combined fruit and vegetable consumption, lunchtime
      vegetable consumption among girls, and daily fruit consumption as well as the
      proportion of total daily calories attributable to fruits and vegetables.
      CONCLUSIONS: Multicomponent school-based programs can increase fruit and
      vegetable consumption among children. Greater involvement of parents and more
      attention to increasing vegetable consumption, especially among boys, remain
      challenges in future intervention research.

PMID- 9551003
TI  - Prevalence and impact of disabling chronic conditions in childhood.
AB  - OBJECTIVES: This study provides a current national profile of the prevalence and
      impact of chronic conditions causing childhood disability. Disability is defined
      as a long-term reduction in ability to conduct social role activities, such as
      school or play, because of a chronic physical or mental condition. METHODS: A
      cross-sectional descriptive analysis was performed on data from 99513 children
      younger than 18 years who were included in the 1992-1994 National Health
      Interview Survey. The response rate exceeded 93% during each year. RESULTS: A
      significant proportion of children, estimated at 6.5% of all US children,
      experienced some degree of disability. The most common causes of childhood
      disability were respiratory diseases and mental impairments. Prevalence of
      disability was higher for older children, boys, and children from low-income and
      single-parent families. Childhood disability is estimated to result in 66 million
      restricted activity days annually, including 24 million days lost from school.
      Furthermore, disability in childhood results in an added 26 million physician
      contacts and 5 million hospital days annually. CONCLUSIONS: Childhood disability
      has profound impacts on children, the education system, and the health care
      system.

PMID- 9551004
TI  - Variation between studies in reported relative risks associated with
      hypertension: time trends and other explanatory variables.
AB  - OBJECTIVES: This study examined the variation in reported relative risks of
      coronary heart disease and stroke associated with hypertension and determined
      reasons for the interstudy variation. METHODS: Studies published since 1970 were
      examined that reported the absolute number of events and person-years for men by
      age and hypertensive status. The data were pooled in Poisson regression models
      with the coronary heart disease or stroke rate as the dependent variable.
      Independent variables were hypertensive status, age at entry, age of study,
      duration of follow-up, diastolic blood pressure cut-off point, and interactions
      of all these variables with hypertensive status. RESULTS: The reported relative
      risks associated with hypertension ranged from 1.45 to 2.77 for coronary heart
      disease and from 1.86 to 5.78 for stroke. Smaller relative risks were found in
      more recent studies, in studies with long follow-up, and in studies using a lower
      cut-off point to define hypertension. CONCLUSIONS: Part of the interstudy
      variation in relative risks associated with hypertension can be attributed to
      differences in duration of follow-up, blood pressure cutoff point, and time at
      which blood pressure was measured, suggesting declining relative risks over time.

PMID- 9551005
TI  - Body mass index and mortality in nonsmoking older adults: the Cardiovascular
      Health Study.
AB  - OBJECTIVES: This study assesses the relationship of body mass index to 5-year
      mortality in a cohort of 4317 nonsmoking men and women aged 65 to 100 years.
      METHODS: Logistic regression analyses were conducted to predict mortality as a
      function of baseline body mass index, adjusting for demographic, clinical, and
      laboratory covariates. RESULTS: There was an inverse relationship between body
      mass index and mortality; death rates were higher for those who weighed the
      least. Inclusion of covariates had trivial effects on these results. People who
      had lost 10% or more of their body weight since age 50 had a relatively high
      death rate. When that group was excluded, there was no remaining relationship
      between body mass index and mortality. CONCLUSIONS: The association between
      higher body mass index and mortality often found in middle-aged populations was
      not observed in this large cohort of older adults. Over-weight does not seem to
      be a risk factor for 5-year mortality in this age group. Rather, the risks
      associated with significant weight loss should be the primary concern.

PMID- 9551006
TI  - Modeling all-cause mortality: projections of the impact of smoking cessation
      based on the NHEFS. NHANES I Epidemiologic Follow-up Study.
AB  - OBJECTIVES: A model that relates clinical risk factors to subsequent mortality
      was used to simulate the impact of smoking cessation. METHODS: Survivor functions
      derived from multivariate hazard regressions fitted to data from the first
      National Health and Nutrition Examination Survey (NHANES I) Epidemiologic
      Followup Study, a longitudinal survey of a representative sample of US adults,
      were used to project deaths from all causes. RESULTS: Validation tests showed
      that the hazard regressions agreed with the risk relationships reported by
      others, that projected deaths for baseline risk factors closely matched observed
      mortality, and that the projections attributed deaths to the appropriate levels
      of important risk factors. Projections of the impact of smoking cessation showed
      that the number of cumulative deaths would be 15% lower after 5 years and 11%
      lower after 20 years. CONCLUSIONS: The model produced realistic projections of
      the effects of risk factor modification on subsequent mortality in adults,
      Comparison of the projections for smoking cessation with estimates of the risk
      attributable to smoking published by the Centers for Disease Control and
      Prevention suggests that cessation could capture most of the benefit possible
      from eliminating smoking.

PMID- 9551007
TI  - Informed consent for HIV testing in a South African hospital: is it truly
      informed and truly voluntary?
AB  - OBJECTIVE: The purpose of this study was to assess informed consent to human
      immunodeficiency virus (HIV) testing in a perinatal HIV transmission study in a
      major referral hospital serving a largely Black population in South Africa.
      METHODS: First-time antenatal clinic attenders who were randomly selected from
      those enrolled in the perinatal HIV study (n = 56) answered questionnaires before
      and after counseling. RESULTS: Knowledge of HIV transmission and prevention, high
      at the outset, was little improved after counseling. The acceptance rate for HIV
      testing was high. Despite assurances that participation was voluntary, 88% of the
      women said they felt compelled to participate in the study. CONCLUSIONS: Informed
      consent in this setting was truly informed but not truly voluntary.

PMID- 9551008
TI  - Differences in the risk of homicide and other fatal injuries between postpartum
      women and other women of childbearing age: implications for prevention.
AB  - OBJECTIVES: This study compared injury deaths between postpartum women and other
      women aged 15 to 44. METHODS: Risk ratios and 95% confidence intervals (CIs) were
      computed for injury fatality rates. RESULTS: Fifty percent (29/58) of postpartum
      injury deaths were homicides, compared with 26% (427/1648) of injury deaths among
      nonpregnant, nonpostpartum women. For females aged 15 to 19, the homicide rate
      was 2.6 times higher (95% CI = 1.17, 5.95) for postpartum females than for other
      females. The motor-vehicle fatality rate was lower for postpartum females than
      for nonpregnant, nonpostpartum females (risk ratio = 0.30, CI = 0.18, 0.48).
      CONCLUSIONS: Postpartum females aged 15 to 19 years were at higher risk of
      homicide. Postpartum women were at reduced risk of motor-vehicle fatalities.

PMID- 9551009
TI  - Facilitating condom use with clients during commercial sex in Nevada's legal
      brothels.
AB  - OBJECTIVES: This study examined condom use in legal Nevada brothels. METHODS:
      Forty female prostitutes in two brothels were interviewed about client resistance
      to condoms and techniques for facilitating condom use. RESULTS: Of 3290 clients
      in the previous month, 2.7% (95% confidence interval [CI] = 2.2%,3.4%) were
      reluctant to use condoms. Of these individuals, 72% ultimately used condoms,
      while 12% chose nonpenetrative sex without condoms. The remaining 16% left the
      brothels without services. Condom use rates were markedly lower with nonpaying
      sex partners (lowers) than with clients. CONCLUSIONS: Brothel prostitutes may be
      at greater risk for acquiring HIV and other sexually transmitted diseases from
      lovers than from clients.

PMID- 9551011
TI  - Family planning in China: out of control?
AB  - OBJECTIVES: This study examined sex ratios in 6 counties in China. METHODS: Data
      from a household survey (n = 5756) were retrospectively analyzed. RESULTS: A
      normal sex ratio was found for children less than 18 years of age. Significant
      differences in sex ratios and family size were observed between the household
      survey data and population registers. CONCLUSIONS: The findings indicate a high
      number of unregistered female births and are consistent with calls for a
      rethinking of Chinese population policies in the direction of a more
      collaborative policy based on female education and participation.

PMID- 9551010
TI  - Reducing pregnancy and induced abortion rates in China: family planning with
      husband participation.
AB  - OBJECTIVES: This study assessed the effectiveness of a family planning
      intervention with and without husband's participation in reducing pregnancy and
      abortion rates in Shanghai, China. METHODS: In this 3-arm randomized trial among
      1800 nonsterilized married women, educational interventions targeting both
      spouses and targeting the wife only were compared with usual family planning
      care. RESULTS: Among women not using intrauterine devices (IUDs), the
      intervention with husband's participation had an effect in reducing pregnancy
      rates (adjusted odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.12, 1.1)
      and abortion rates (adjusted OR = 0.29, CI = 0.09, 0.94) compared with control
      subjects, and a significant effect in reducing pregnancy rates (adjusted OR =
      0.29, CI = 0.10, 0.85) and abortion rates (adjusted OR = 0.24, CI = 0.07, 0.77)
      compared with wife-only subjects. CONCLUSIONS: Family planning interventions
      involving husbands may reduce pregnancy and abortion rates among non-IUD users.

PMID- 9551012
TI  - Infant mortality differences between whites and African Americans: the effect of
      maternal education.
AB  - OBJECTIVES: Despite decreasing infant mortality in North Carolina, the gap
      between African Americans and Whites persists. This study examined how racial
      differences in infant mortality vary by maternal education. METHODS: Data came
      from Linked Birth and Infant Death files for 1988 through 1993. Multiple logistic
      regression models adjusted for confounders. RESULTS: Infant mortality risk ratios
      comparing African Americans and Whites increased with higher levels of maternal
      education. Education beyond high school reduced risk of infant mortality by 20%
      among Whites but had little effect among African Americans. CONCLUSIONS: Higher
      education magnifies racial differences in infant mortality on a multiplicative
      scale. Possible reasons include greater stress, fewer economic resources, and
      poorer quality of prenatal care among African Americans.

PMID- 9551013
TI  - Rates and independent correlates of Pap smear testing among Korean-American
      women.
AB  - OBJECTIVES: This study reports population estimates of Pap smear testing among
      Korean-American women and evaluates correlates of testing. METHODS: Korean
      Americans in 2 California counties were surveyed by telephone. Frequencies were
      age-adjusted to the 1990 census to produce population estimates of testing.
      Logistic regression models were used to evaluate independent correlates of
      testing RESULTS: Only 50% of the Korean-American women surveyed had a Pap test in
      the previous 2 years. The strongest independent correlate was having had a
      regular check-up in the previous 2 years (odds ratio 7.2, 95% confidence interval
      4.2, 12.1). CONCLUSIONS: Rates of Pap testing among Korean-American women are
      well below national objectives. Collaboration and community-sensitive research
      are essential to collect data and design programs to improve the health of ethnic
      minority communities.

PMID- 9551014
TI  - Contraception and abortion in two Vietnamese communes.
AB  - OBJECTIVES: The authors examined factors predicting abortion use in two communes
      in northern Vietnam. METHODS: A survey of 504 rural and 523 urban women of
      childbearing age was conducted. RESULTS: For the 13.6% of urban and 19% of rural
      commune women having had an abortion in the previous year, logistic regression
      analyses demonstrated that use of an intrauterine device reduced the likelihood
      of subsequent abortion in both communes. Traditional method use in the rural
      commune, however, increased women's likelihood of a subsequent abortion.
      CONCLUSIONS: Contraceptive use in these 2 communes affected abortion more than
      sociodemographic factors. Traditional method use by rural women is a risk for
      abortion.

PMID- 9551015
TI  - Differences in preconceptional and prenatal behaviors in women with intended and
      unintended pregnancies.
AB  - OBJECTIVES: This study examined whether pregnancy intention was associated with
      cigarette smoking, alcohol drinking, use of vitamins, and consumption of
      caffeinated drinks prior to pregnancy and in early pregnancy. METHODS: Data from
      a telephone survey of 7174 pregnant women were analyzed. RESULTS: In comparison
      with women whose pregnancies were intended, women with unintended pregnancies
      were more likely to report cigarette smoking and less likely to report daily
      vitamin use. Women with unintended pregnancies were also less likely to decrease
      consumption of caffeinated beverages or increase daily vitamin use. CONCLUSIONS:
      Pregnancy intention was associated with health behaviors, prior to pregnancy and
      in early pregnancy, that may influence pregnancy course and birth outcomes.

PMID- 9551016
TI  - The impact of mammography quality improvement legislation in Michigan:
      implications for the National Mammography Quality Standards Act.
AB  - OBJECTIVES: This study examined the impact of state legislation on mammography
      quality and access in Michigan. METHODS: The impact of state legislation was
      analyzed with respect to utilization, numbers of machines and facilities, and
      image quality. RESULTS: The legislation had a positive effect on image quality
      improvement, had no impact on utilization by women aged 50 years and above, and
      resulted in few facility closures. CONCLUSIONS: Michigan's legislative
      intervention appears to have had a positive effect on efforts to improve
      mammography quality assurance with implications for other federal and state
      efforts to achieve quality assurance in health care delivery.

PMID- 9551017
TI  - Reporting sexual risk behavior for HIV: a practical risk index and a method for
      improving risk indices.
AB  - OBJECTIVES: As a means of enhancing public health efforts to control sexual
      transmission of human immunodeficiency virus (HIV), methods were developed to
      report on risk behavior in a manner that is comparable and widely interpretable.
      METHODS: An elementary sexual behavior risk index (the vaginal episode equivalent
      index) that is in accord with some of the essential knowledge about sexual
      transmission of HIV is described, and a multivariate ordinal risk (MOR) method
      that can be used to improve such risk indices is introduced. RESULTS: An example
      shows that these approaches are applicable to observational studies of
      seroconversion. CONCLUSIONS: The MOR represents a powerful new tool to develop
      valid comparable measures of sexual risk behavior and, thereby, to advance HIV
      prevention research.

PMID- 9551018
TI  - Evaluation of a public-private certified nurse-midwife maternity program for
      indigent women.
AB  - OBJECTIVES: This study assessed the impact of a public-private certified nurse
      midwife program on prenatal and delivery outcomes among medically indigent women.
      METHODS: A population-based quasi-experimental design was used to compare 1
      intervention county with 2 nonintervention counties. RESULTS: The program
      significantly reduced the number of women who received no prenatal care and the
      risk of acquiring less than adequate prenatal care. Reductions in the proportion
      of infants born premature or with low birth-weights were of borderline
      significance. The use of induction and/or stimulation of labor was statistically
      elevated. CONCLUSIONS: These results suggest that the intervention program was
      instrumental in reducing some, but not all, negative prenatal and delivery
      outcomes.

PMID- 9551019
TI  - Eliminating iodine deficiency in rural Sarawak, Malaysia: the relevance of water
      iodization.

PMID- 9551020
TI  - Promoting sunscreen in a community drugstore.

PMID- 9551021
TI  - Few smokers know their cigarettes have filter vents.

PMID- 9551022
TI  - Anonymous HIV testing.

PMID- 9551023
TI  - HIV testing.

PMID- 9551024
TI  - Not all behavior change is equivalent.

PMID- 9551025
TI  - Outbreak of serogroup C meningococcal disease among preschool-aged children:
      Illinois, 1996.

PMID- 9551026
TI  - Health Check--smart eating made simple. The Heart and Stroke Foundation of
      Canada.

PMID- 9551027
TI  - Online cardiology journals--the desktop library.

PMID- 9551028
TI  - Choosing among drugs of different price for similar indications.

PMID- 9551029
TI  - Comparison of efficacy and cost among lipid-lowering agents in patients with
      primary hypercholesterolemia.
AB  - OBJECTIVE: To compare efficacy and cost of lipid-lowering agents in patients with
      primary hypercholesterolemia. DESIGN: A meta-analysis was conducted to determine
      estimates of efficacy for lipid-lowering agents. Efficacy was defined as the
      change in the ratio of total cholesterol:high density lipoprotein (HDL) induced
      by treatment. This ratio was selected because of its good predictive value for
      the risk of coronary disease. Lipid-lowering agents were grouped into three
      categories according to the decrease in the total cholesterol:HDL ratio.
      Acquisition prices for drugs were obtained from the Quebec provincial drug
      formulary. An analysis determined which drugs in each category 'purchased' the
      greatest decrease in ratio for the lowest cost. SETTING: Clinical trial study
      centres. PATIENTS: The population analyzed had a mean baseline total
      cholesterol:HDL ratio of 7.3, an average age of 50.5 years and mean proportion of
      men of 62.5%. INTERVENTIONS: Twelve lipid-lowering therapies at various doses
      were investigated. RESULTS: Drugs that were more recently introduced had the
      greatest effect on the total cholesterol:HDL ratio. A direct dose-effect
      relationship was not evident, although there was a trend in this direction. In
      each of the three categories, there was wide range of cost, suggesting that the
      same effect is available at a broad range of prices. The drugs with the greatest
      effect on the ratio at the lowest cost were fluvastatin 60 mg/day, fenofibrate
      (micronized) 200 mg/day and simvastatin 20 mg/day. CONCLUSION: These results can
      be useful for clinicians in the selection of agents that achieve a specified goal
      of therapy at the lowest cost.

PMID- 9551030
TI  - Physician specialty is associated with differences in warfarin use for atrial
      fibrillation.
AB  - OBJECTIVE: To determine whether physician specialty is associated with
      prescription of warfarin to elderly persons with atrial fibrillation. DESIGN:
      Cross-sectional survey. SETTING: One hundred and thirty-eight randomly selected
      general practitioners--all 58 internists and all 27 cardiologists in southern
      Alberta were surveyed by mail. INTERVENTION: Physicians identified their
      preferred drug for stroke prevention generally and in response to two
      hypothetical cases. MAIN RESULTS: Response rates were 66% (general
      practitioners), 76% (internists) and 89% (cardiologists). Specialists (92%) were
      more likely than general practitioners (76%) to choose warfarin (P = 0.007).
      Findings were similar for questions related to case scenarios; however, the
      magnitude of differences between specialists and general practitioners was less
      pronounced. Specialists were more likely (77%) to prescribe warfarin for elderly
      females than were general practitioners (62%, P = 0.08). Similar proportions of
      specialists (77%) and general practitioners (67%) would prescribe warfarin to
      elderly males. CONCLUSION: Physician specialty is associated with warfarin
      prescription for elderly persons with atrial fibrillation.

PMID- 9551031
TI  - Preparation, attitudes and behaviour in nonhospital cardiac emergencies:
      evaluating a community's readiness to act.
AB  - OBJECTIVE: To determine how people in a moderately sized Ontario city believe
      they will react if they witness someone colapsing. DESIGN: Telephone survey.
      SETTING: The cities of Kitchener and Waterloo, part of the Regional Municipality
      of Waterloo, Ontario, with a combined population of 378,000. PARTICIPANTS:
      Households were randomly contacted and a questionnaire was administered, provided
      the respondent was over 44 years of age and agreed to be interviewed. Of 2479
      households with eligible respondents, 811 (33%) completed the questionnaire.
      OUTCOMES: Age, sex, educational level, cardiac risk factors and cardiopulmonary
      resuscitation (CPR) training of respondents were determined, as well as actions
      they would take if cardiac arrest occurred in a family member at home or in
      stranger in the street, and associated emotions and barriers to implementing
      actions. RESULTS: Among the first three actions that respondents who were not
      prompted with possible responses said they would take, 311 (72%) witnessing a
      collapse at home, compared with 166 (44%) witnessing a collapse on the street,
      would call 911, the police or an ambulance. Other 'first three actions' in home
      collapse were checking for breathing (120 [28%]), checking for pulse (91 [21%])
      and administering CPR (34 [8%]); these actions were less commonly selected in
      response to a strangers collapse and when respondents were not prompted.
      Respondents felt they would be more likely to perform CPR on a friend than on a
      stranger (OR 1.38, 95% CI 1.10 to 1.58). When asked how likely they would be to
      perform specific acts when witnessing a collapse, 254 (69%) of respondents
      thought they would call their family doctor and 179 (48%) thought they were
      likely to begin chest compressions. Barriers to performing CPR centred around
      legalities and disease transmission. CONCLUSION: Older people do not know how to
      act effectively in a cardiac emergency. Traditional CPR and public awareness
      programs have been ineffective in reaching this population; alternative means are
      required to help the public respond more effectively to cardiac emergencies.

PMID- 9551032
TI  - Postoperative laboratory and imaging investigations in intensive care units
      following coronary artery bypass grafting: a comparison of two Canadian
      hospitals.
AB  - OBJECTIVES: To compare the utilization and cost of common laboratory and imaging
      tests following admission to the intensive care unit (ICU) after coronary artery
      bypass surgery in two hospitals. The hospitals use different strategies to order
      tests postoperatively: one hospital uses a mandated protocol while the other does
      not. DESIGN: Demographic and testing data were prospectively collected in both
      hospitals as part of an ongoing ICU management program. Thirteen commonly
      performed laboratory tests or imaging procedures were compared. Average costs for
      each test were calculated, and utilization and cost of testing were compared per
      admission and per day in ICU. SETTING: Two tertiary care ICUs in different
      Canadian cities. PATIENTS: Consecutive patients admitted to ICU following
      coronary artery bypass graft surgery over a two-year period. MAIN RESULTS: There
      were 415 admissions to the Health Sciences Centre in Winnipeg, Manitoba and 504
      to the Jewish General Hospital (JGH) in Montreal, Quebec. There were no
      demographic, length of stay or ICU mortality differences. A postoperative
      protocol for ordering investigations is used at JGH. Striking differences in test
      utilization were noted, with more investigations performed per admission and per
      unit day at JGH (P < 0.001). The average cost of the investigations was greater
      at JGH ($160 more per admission; $75 more per intensive care day). CONCLUSIONS:
      There are marked differences in the investigation pattern and costs for coronary
      artery bypass patients admitted to ICU in these hospitals. It is suggested that
      the benefits of frequent routine determinations of bloodwork, electrocardiograms
      and chest radiographs should be reevaluated in this patient population.

PMID- 9551033
TI  - Effects of combined endurance and strength training on left ventricular
      morphology in male and female rowers.
AB  - The effects of 10 weeks of combined endurance and strength training on left
      ventricular (LV) morphology, muscular strength, maximal oxygen consumption
      (VO2max) and rowing performance were assessed. Twenty-five subjects (eight males,
      mean age 23.0 +/- 6.1 years, and 17 females, 22.7 +/- 5.0 years) were tested at
      baseline and after five and 10 weeks of training. Combined training was
      associated with significant improvements in VO2max, rowing performance and
      muscular strength after 10 weeks of training. A significant increase in LV
      diastolic dimension was found in males after 10 weeks of training; however, no
      significant alteration was found for any other measured echocardiographic
      variable. Therefore, with the exception of LV diastolic dimension in males, 10
      weeks of combined endurance and strength training appears to be an insufficient
      stimulus to elicit significant alterations in LV morphology despite changes in
      VO2max, muscular strength or rowing performance.

PMID- 9551034
TI  - Canadian Consensus Conference on Adult Congenital Heart Disease 1996.

PMID- 9551035
TI  - Regulators of apoptosis in the heart: a matter of life and death.
AB  - Programmed cell death or apoptosis is an active physiological process that
      permits the removal of unwanted or damaged cells from the body through an
      intrinsic cell-suicide program. Apoptosis is characterized by condensation of the
      nucleus and cytoplasm without loss of membrane integrity. The occurrence of
      apoptosis in the vasculature and myocardium has recently been described.
      Inappropriate loss of myocardial cells is suggested to contribute to conduction
      defects and ventricular remodelling after injury. The molecular mechanisms that
      regulate programmed cell death in cardiac muscle cells are poorly defined.
      However, recent evidence has suggested that specific genes can either provoke or
      prevent apoptosis. In this regard, the tumour suppressor protein p53 has been
      proposed to mediate apoptosis, while the Bcl-2 protein prevents it. Prevention of
      apoptosis in the heart is potentially of significant therapeutic value given the
      limited capacity of the heart to repair itself after injury. This study
      determined that the expression of p53 in ventricular myocytes is sufficient to
      trigger apoptosis. Moreover, p53 results in a significant increase in the
      expression of the death-promoting protein Bax. Importantly, the antiapoptotic
      factor Bcl-2 is sufficient to prevent p53-mediated apoptosis and p53-dependent
      transcription of Bax in ventricular myocytes. The data substantiate a role for
      p53 and Bcl-2 as crucial regulators of apoptosis in the heart.

PMID- 9551036
TI  - Coronary artery fistula after cardiac transplantation.
AB  - A cardiac transplant recipient with multiple coronary artery fistulae draining
      into the right ventricle is described. These fistulae presumably resulted from
      repeated endomyocardial biopsies. The diagnosis of coronary artery fistulae was
      made at the annual coronary arteriography. The magnitude of the shunt remained
      small over eight years of follow-up.

PMID- 9551037
TI  - [Increased occurrence of esophageal hypermotility disorders in patients with
      arterial hypertension].
AB  - BACKGROUND AND OBJECTIVE: It has been noted in previous manometric examinations
      of the oesophagus in patients with chest pain that abnormal motility was often
      associated with arterial hypertension. A systematic study of this relationship
      was therefore undertaken. PATIENTS AND METHODS: In 40 patients with chest pain
      (18 women and 22 men, mean age 54.7 [24-70] years) and in 20 healthy volunteers
      (12 men, 8 women, mean age 50.8 [22-63] years) standardized oesophageal manometry
      and arterial blood pressure monitoring were performed over 24 hours. Coronary
      heart disease and gastrointestinal lesions had been excluded by angiography and
      endoscopy, respectively. RESULTS: 20 patients (group H) had hypertension (median
      24-hour blood pressure > 135/85 mmHg), while 20 patients (group N) and the normal
      controls (group K) were normotensive. Oesophageal manometry data differed
      significantly between the three groups regarding distal pressure amplitude (in
      hPa [hectopascals]; group H: 62 hPa*,**, group N 44 hPa* and group K 36 hPa**;
      [*P < 0.0005]) and the proportion of simultaneous contractions (group H 23%,
      group N 22%**, group K 10%***; ***P < 0.001). The hypertensive patients had
      significantly more frequent motility abnormalities than normal controls (13/20 vs
      4/20, P < 0.001); while normotensive patients had more frequent episodes of
      abnormal propulsion in the oesophagus (proportion of propulsive contractions in
      group H: 53%, in N: 44%, in K: 59%; P < 0.01). CONCLUSION: Oesophageal motility
      differed significantly in patients with chest pain from that in healthy controls.
      Patients with chest pain and hypertension more frequently had oesophageal
      hypermotility. This suggests a generalized abnormality of smooth muscle.

PMID- 9551038
TI  - [Polyposis of the gastrointestinal tract as a manifestation of diffuse follicular
      lymphatic hyperplasia].
AB  - HISTORY AND ADMISSION FINDINGS: A 21-year-old previously healthy Turkish man who
      had been living in Germany for 15 years was admitted because of worsening cramp
      like abdominal pain with nausea, vomiting and watery diarrhoea. Palpation
      elicited diffuse muscular guarding over the entire abdomen and a mass of about 8
      cm in the right lower abdomen. INVESTIGATIONS: Abnormal laboratory results were
      erythrocyte sedimentation rate (55 mm), C-reactive protein (6.2 mg/dl), total
      bilirubin (2.1 mg/dl), creatine kinase (137 U/l) and thymidine kinase (5.5 U/l).
      There was a slight leucocytosis (13,700/microliter) and mild anaemia (haemoglobin
      13.4 g/dl) with a normal differential count. Listeria ivanovii was repeatedly
      cultured from stool. Ultrasonography and computed tomography of the abdomen
      demonstrated a 6 cm mass in the right lower abdomen, splenomegaly (15.5 x 5 cm)
      and several lymphomas, up to 1.8 cm in diameter. Endoscopy revealed dense, in
      part grass-like, polyps, 3 to 6 mm deep, in the mucosa from the terminal ileum to
      the rectum, and to a lesser extent also in the duodenum. Histological examination
      of the polyps demonstrated diffuse follicular hyperplasia without evidence of
      malignancy. TREATMENT AND COURSE: On antibiotic treatment with ofloxacin (2 x 400
      mg intravenously) the symptoms quickly regressed, but the endoscopic findings
      remained unchanged. CONCLUSION: Diffuse follicular lymphatic hyperplasia
      manifested itself in this patient as diffuse gastrointestinal polyposis. Listeria
      ivanovii cannot be ruled out as a causative factor.

PMID- 9551039
TI  - [Lead poisoning caused by a Greek ceramic cup].
AB  - HISTORY AND ADMISSION FINDINGS: A 24-year-old woman, an administrative employee,
      was admitted with colicky abdominal pain and constipation, as well as breathing
      related chest pain of recent onset with cough and sometimes blood-streaked
      sputum. She had previously been unsuccessfully treated for gastritis and
      adnexitis. On physical examination revealed diffuse, ill-defined abdominal pain
      on pressure and mild tachycardia, but was otherwise unremarkable. INVESTIGATIONS:
      Electrocardiogram, chest radiogram, lung scintigraphy, abdominal sonography,
      oesophago-gastro-duodenoscopy and gynaecological examination indicated nothing
      abnormal. Laboratory tests showed microcytic anemia, slight leucocytosis and
      anisocytosis, as well as polychromasia and basophilic stippling of erythrocytes.
      The 24-h urinary porphyrin concentration was elevated. DIAGNOSIS TREATMENT AND
      COURSE: Precise differentiation of porphyrins in urine, stool and erythrocytes by
      enzymatic measurement first raised the suspicion of lead poisoning. Whole-blood
      lead concentration was markedly raised to 600 micrograms/l (normal up to 90
      micrograms/l) and 170 micrograms/dl in urine (normal up to 80 micrograms/dl). A
      ceramic cup from Greece was traced as the source of the lead, the patients having
      regularly for over 2 1/2 months drunk lemon instant-tea from it. She was treated
      with oral doses of DMPS (sodium salt of 2,3-dimercapto-1-propanesulphonic acid),
      5-10 mg/kg 3x daily for 2 days, followed by 2.5 mg/kg 2 x daily, until lead
      concentrations in blood and urine had become normal, when all symptoms
      disappeared: detoxification was complete within 4 months. CONCLUSION: This case
      impressively illustrates how difficult it can be to diagnose lead poisoning and
      identify its source. Oral DMPS is a practicable and efficacious form of
      treatment.

PMID- 9551040
TI  - [The treatment of aortic isthmus stenosis in adults using balloon dilatation and
      stent implantation].

PMID- 9551041
TI  - [Interventional catheter closure of interatrial shunt connections in adults].

PMID- 9551042
TI  - [Glycyrrhizin for the treatment of allergic diseases and chronic hepatitis].

PMID- 9551043
TI  - [Smoking and hyperkinetic syndrome].

PMID- 9551044
TI  - [Megaloblastic anemia caused by nutritional errors].

PMID- 9551045
TI  - Endovascular treatment of isolated iliac artery aneurysms.

PMID- 9551046
TI  - Endovascular interventions into the 21st century: what can we anticipate?

PMID- 9551047
TI  - Prevention of spinal cord ischaemic complications after thoracoabdominal aortic
      surgery.
AB  - Since the publication of prior reviews on this topic, substantial clinical
      experience with a variety of operative strategies to prevent ischaemic cord
      complications has been reported. The available data on angiographic localisation
      of critical intercostal vessels, and, in particular, the evoked potential
      response to cross-clamping in patients indicates that risk of paraplegia varies
      considerably even among patients with equivalent TAA extent. Factors such as
      individual development of the ASA, patent critical intercostals, and the
      particulars of collateral circulation when intercostal aortic ostia are already
      occluded likely account for this variability. Information available from SSEP
      monitoring relative to the dynamic course of cord ischaemia with cross-clamping,
      and the parallel, if not, frustrating experience with angiographic localisation
      and intercostal vessel reconstruction indicates that a narrow temporal threshold
      of cord ischaemia with clamping is present in many patients. This reinforces the
      importance of both expeditious clamp intervals, critical intercostal re
      anastomoses, and the desirability of neuroprotective manoeuvres during cross
      clamp induced cord ischemia. As suggested in compelling experimental work our
      contemporary clinical experience, and predicted by prior reviewers, regional cord
      hypothermia provides significant promise for limiting or eliminating, in
      particular, immediate perioperative deficits. Avoidance of postoperative
      hypotension, spinal cord oedema, and preservation of critical intercostal vessels
      are additional strategies necessary to impact the development of delayed deficits
      favourably.

PMID- 9551048
TI  - Surgery on aneurysms in Byzantine times (324-1453 A.D.).

PMID- 9551049
TI  - The increasing activity of a vascular ultrasound service.
AB  - OBJECTIVES: To examine the change in activity of a vascular ultrasound service
      over 7 years. DESIGN: Retrospective review. SETTING: Vascular studies unit,
      University hospital. METHOD: Audit of the number of vascular ultrasound tests
      carried out over the last 7 years using a prospective computerised database.
      RESULTS: Data shows that the overall workload has tripled over the 7-year period.
      In addition the complexity of investigations has increased during this time. The
      number of carotid scans has increased four-fold while the number of graft
      surveillance scans and vein scans has increased seven-fold. Assessment of lower
      limb arteries has developed from simple pressure measurements to detailed
      ultrasound scans and, as a consequence, the number of diagnostic angiograms has
      fallen by 75%. The factors that have influenced these changes are discussed.
      CONCLUSIONS: There has been an important increase in the role of colour Doppler
      ultrasound as it becomes the "first line" vascular diagnostic test. However this
      trend can only continue if vascular ultrasound services are appropriately
      resourced. It is therefore essential to maintain an efficient audit system.

PMID- 9551050
TI  - Outcome of infrainguinal bypass surgery for critical leg ischaemia in patients
      with chronic renal failure.
AB  - OBJECTIVE: To determine whether infrainguinal bypass surgery is worthwhile in
      patients with critical limb ischaemia (CLI) and chronic renal failure. DESIGN:
      Longitudinal observational study. MATERIALS AND METHODS: Twenty-two patients with
      moderate renal failure indicated by serum creatinine level above 150 mumol/l, 10
      patients with end-stage renal disease requiring dialysis, and three patients with
      functioning kidney transplant, underwent 39 bypass procedures for critical limb
      ischaemia. RESULTS: Six femoropopliteal, 14 femorocrural and 19 femoropedal
      bypasses were performed. The immediate, 1-month, and 1-year primary patency rates
      were 97%, 84% and 70%, respectively. The limb salvage was 93% at 1-month and 72%
      at 1-year follow-up. One-year patency and leg salvage rates were 81% and 79% in
      non-dialysis patients, and 47% and 37% in dialysis patients. At 1-year follow-up,
      55% of surviving patients had salvaged limbs. None of the patients in dialysis
      was alive with salvaged legs 4 months after revascularisation. Among preoperative
      risk factors, only serum creatinine showed a statistical significance in
      predicting leg salvage and survival. CONCLUSIONS: As the outcome of patients on
      dialysis is very poor after infrainguinal bypass grafting, revascularisation is
      seldom indicated. On the contrary, leg salvage can achieve good results in
      patients not requiring dialysis.

PMID- 9551051
TI  - Combined aortorenal reconstruction: is there an optimum method of exposure?
AB  - OBJECTIVE: To determine the advantages and disadvantages of two different
      transabdominal approaches to expose the pararenal aorta; infacolic (IC) and
      medical visceral rotation (MVR). DESIGN: Retrospective study. METHODS: We
      reviewed a consecutive series of concurrently treated patients undergoing
      combined aortorenal reconstruction using one of these two approaches (IC n = 45;
      MVR n = 30). RESULTS: The two groups were identical with respect to demographics,
      risk factors and associated illnesses. Aortic aneurysmal disease predominated
      among MVR patients, and occlusive disease among IC patients (p = 0.001). The most
      common aortic reconstruction was aortofemoral bypass grafting. Renal
      revascularisation was most often performed for symptoms; only in the MVR group it
      was the result of involvement by aortic aneurysmal disease (p = 0.000).
      Thromboendarterectomy was the most common renal reconstruction, though performed
      only 10 times in the MVR group (p = 0.01). Except for supraceliac aortic cross
      clamping, which was required more often in the MVR group (p = 0.004), operative
      details did not differ between the groups. Although the overall perioperative
      mortality and complication rate were equal, intraoperative splenic injury
      occurred solely in the MVR group (p = 0.001), and these patients experienced more
      pulmonary complications (p = 0.004) and they were hospitalised longer than the IC
      group (29.7 +/- 35.8 vs. 17.2 +/- 15.4 days; p = 0.04). CONCLUSIONS: MVR has
      increased morbidity, but its unrestricted continuous exposure is optimum for
      combined aortorenal reconstruction involving pararenal aneurysmal disease.
      Pararenal occlusive disease is adequately exposed in most cases by the IC
      approach.

PMID- 9551052
TI  - Chlamydia pneumoniae in human abdominal aortic aneurysms.
AB  - OBJECTIVES: To investigate the presence of Chlamydia pneumoniae DNA in the wall
      of infrarenal abdominal aortic aneurysms, and in the wall of non-aneurysmal
      infrarenal abdominal aortas. DESIGN: Case-control study. MATERIALS AND METHODS:
      The study group consisted of 40 patients operated transperitoneally for an
      infrarenal abdominal aortic aneurysm (IAAA) (eight females, 32 males; mean age 69
      years, median age 68 years). Specimens from the aneurysm wall were taken
      peroperatively under sterile conditions. The control group consisted of 40
      deceased persons without aortic aneurysms (14 females, 26 males; mean age 71
      years, median age 70 years). Specimens from the non-aneurysmal infrarenal aortas
      (NIAA) were collected within 48 h after death. The specimens from both groups
      were frozen at -70 degrees C immediately after collection. A nested polymerase
      chain reaction (PCR) method, using two sets of primers designed to detect a
      fragment of the major outer membrane protein gene of C. pneumoniae, was used.
      RESULTS: The detection of C. pneumoniae-specific DNA was significantly higher in
      the study group (14/40 = 35%) than in the control group (2/40 = 5%); (p = 0.001).
      No clinical factor predicting the presence of C. pneumoniae in the aneurysm wall,
      could be found. CONCLUSION: Chlamydia pneumoniae was detected at a significantly
      higher frequency in the wall of IAAAs than in the wall of NIAAs. Although this
      finding does not prove that C. pneumoniae causes IAAAs, further studies on the
      possible role of C. pneumoniae in the pathogenesis of aneurysms should be
      performed.

PMID- 9551053
TI  - Operative mortality and long-term survival of patients operated on for acute
      lower limb ischaemia.
AB  - OBJECTIVES: To investigate the operative mortality and long-term survival of
      patients with lower limb embolism or acute thrombosis. DESIGN: A retrospective
      survival analysis. MATERIALS: Eighty patients with acute thrombosis treated by
      bypass and 192 patients with embolism treated by embolectomy during the years
      from 1985 to 1996 were studied. METHODS: The observed survival rates were
      calculated with the product limit method. The expected survival rates were
      estimated from death-rate tables. The standard mortality rate was compared over a
      5-year follow-up. RESULTS: The patients treated for embolism had an operative
      mortality of 17% and a 5-year survival rate of 17%, which was significantly lower
      than the expected rate of 62%. Those treated for acute thrombosis had an
      operative mortality of 14% and a 5-year survival rate of 44%. This was
      significantly higher than for the embolism group, but significantly lower than
      the expected rate of 74%. Both groups had a standard mortality rate of 2.2 at 5
      years. CONCLUSION: Patients with acute ischaemia have a poor short-term and long
      term prognosis. The patients treated for embolism are older and they have a
      shorter life expectancy than those treated for acute thrombosis. The standard
      mortality rate of the two groups appears similar.

PMID- 9551054
TI  - Effect of prolonged pulsatile shear stress in vitro on endothelial cell seeded
      PTFE and compliant polyurethane vascular grafts.
AB  - OBJECTIVES: Compliance mismatch between graft and native artery, and failure of
      the graft to develop an endothelial lining are the two main factors in graft
      failure. The objective of this study was to assess a new compliant graft for
      effective cell attachment and cell retention at physiological levels of pulsatile
      shear stress over a 6-hour period of physiological pulsatile flow. DESIGN:
      Laboratory haemodynamic study. MATERIALS AND METHODS: Human umbilical vein
      endothelial cells labelled with 111In-oxine were seeded on compliant polyurethane
      (CPU) and polytetrafluoroethylene (PTFE) vascular grafts. These were then exposed
      to varying shear stresses of up to 13.8 +/- 0.6 dyn/cm2 using a pulsatile flow
      model. Dynamic scintigraphy images were acquired using a gamma camera linked to
      an on-line computer during 6 h of perfusion and data presented as mean +/-
      standard error of mean. RESULTS: Mean seeding efficiencies were significantly
      different at 4,316 +/- 505 and 825 +/- 504 CPM/cm2 on the CPU and PTFE grafts,
      respectively (p = 0.018). The flow experiment showed a higher percentage of cells
      retained on the CPU graft after exposure to shear stress caused by pulsatile flow
      compared to PTFE with respect to time. After 6 h pulsatile perfusion there was a
      significantly higher proportion of initial cells attached to CPU graft compared
      to PTFE graft (73 +/- 8% vs 42 +/- 8%, p = 0.018). The areas under the time
      activity curves over the 6-hour period were 280 +/- 26.4 for CPU and 176.0 +/-
      30.0 for PTFE, confirming a significant greater total cell loss from PTFE
      compared with CPU grafts (51 +/- 7.0% vs 23 +/- 8.3%, p = 0.018, Wilcoxon matched
      pairs signed-ranks test). CONCLUSIONS: This flow model provides an effective
      method of assessing cell retention on graft materials under physiological
      conditions over a 6-hour period; CPU combines both excellent compliance and
      endothelial cell attachment rates after 6 h exposure to shear stress.

PMID- 9551055
TI  - Influence of surgical experience on the results of carotid surgery. The Finnvasc
      Study Group.
AB  - OBJECTIVE: To assess the 30-day mortality and morbidity rates related to carotid
      endarterectomy on a nation-wide basis. DESIGN: Retrospective cross-sectional
      study based on vascular registry Finnvasc. MATERIALS AND METHODS: A total of
      17,465 recorded vascular and endovascular procedures included exactly 1600
      carotid endarterectomies performed by 104 surgeons in 23 hospitals. Fourteen per
      cent of the patients were operated on for asymptomatic carotid stenosis. RESULTS:
      The combined mortality and permanent stroke rate was 3.3%, without any difference
      between operations done on symptomatic or asymptomatic patients. There was a
      clear inverse association between surgeon's carotid case load and poor outcomes
      in carotid surgery (p < 0.005), the critical patient mass per surgeon and year
      being 10 operations. There was no association between outcome after carotid
      surgery and hospital volume of carotid operations. CONCLUSIONS: Surgeon's
      experience in carotid surgery clearly improves the results of carotid surgery.

PMID- 9551056
TI  - Failure to demonstrate Chlamydia pneumoniae in symptomatic abdominal aortic
      aneurysms by a nested polymerase chain reaction (PCR).
AB  - OBJECTIVE: To investigate whether Chlamydia pneumoniae is present in symptomatic
      abdominal aortic aneurysms (AAA). METHOD AND MATERIALS: After optimisation of DNA
      extraction procedures an inhibitor-controlled nested polymerase chain reaction
      (PCR) amplifying fragments of the gene encoding the C. pneumoniae specific major
      outer membrane protein was performed on 124 wall-specimens from 20 patients with
      symptomatic AAA. RESULTS: None of the specimens contained C. pneumoniae-specific
      DNA. Minor inhibition of the PCR was noticed especially in media specimens.
      CONCLUSION: Using a sensitive and specific nested PCR, we were not able to detect
      C. pneumoniae in symptomatic AAA. The failure to detect C. pneumoniae in
      symptomatic AAA, combined with previously reported positive findings in
      atherosclerotic lesions, supports the hypothesis that AAA and atherosclerosis
      might be two different disease entities.

PMID- 9551057
TI  - Early experience with stenting for iliac occlusive disease.
AB  - OBJECTIVES: To review our experience of iliac artery stenting for occlusive
      disease. DESIGN: Prospective study of 50 consecutive patients with iliac
      occlusive disease, November 1993-November 1996. The indications for stenting were
      complete iliac occlusion (37) restenosis (four), donor site inflow for bypass
      grafting (four) and difficult stenoses (> 90% and/or > 5 cm) (five). The majority
      of patients (41) presented with intermittent claudication. RESULTS: All 13
      stenoses were successfully stented. One occluded but the rest remain patent.
      There were no other complications. By contrast, it was not possible to place a
      stent across 10 of the 37 complete iliac occlusions. In this group there were
      nine major complications, including five patients who required early embolectomy
      (four femoral, one brachial) and one patient who developed a false aneurysm at
      the site of the stent. The "intention to treat" primary cumulative patency for
      iliac occlusions was 65% at 2 years but after excluding technical failures was
      88%. CONCLUSIONS: There is a sharp learning curve and significant complication
      rate associated with stenting complete occlusions. However, following successful
      stenting patency rates are around 90% for both iliac stenoses and occlusions.

PMID- 9551058
TI  - The treatment of aortoiliac occlusions by endovascular stenting with or without
      adjuvant femorofemoral crossover grafting.
AB  - We present four consecutive patients in whom we have used a combination of
      vascular and endovascular techniques in order to revascularise ischaemic legs
      caused by extensive aortoiliac occlusions. We believe that the techniques
      presented offer a viable alternative to more conventional surgical approaches in
      such cases.

PMID- 9551059
TI  - Prevotella buccae bacteraemia associated with infection of a pseudoaneurysm.

PMID- 9551060
TI  - Secondary haemorrhage from saphenous vein grafts caused by methicillin-resistant
      Staphylococcus aureus.

PMID- 9551061
TI  - Recurring aortoenteric fistula.

PMID- 9551062
TI  - Nikolai S. Korotkov: a story of an unknown surgeon with an immortal name.

PMID- 9551063
TI  - Primary pancreatic lymphoma.
AB  - BACKGROUND: Primary pancreatic lymphoma is a rare neoplasm that may be confused
      with pancreatic adenocarcinoma. We reviewed retrospectively our contemporary
      experience with this disease to define more clearly the clinical presentation of
      this disease and the proper role for percutaneous fine-needle aspiration biopsy
      and surgery. METHODS: From 1980 to 1995, 11 patients with primary pancreatic
      lymphoma were treated at The University of Texas M. D. Anderson Cancer Center.
      Patient demographics, radiographic studies, fine-needle aspiration biopsy
      findings, operative procedures, and other treatment data were reviewed. RESULTS:
      The median age of the 11 patients was 64 years (range, 37 to 74 years). Abdominal
      pain was the most common symptom at presentation. Five patients had an elevated
      lactate dehydrogenase level, and only two patients had hyperbilirubinemia.
      Computed tomography scan demonstrated encasement of the superior mesenteric
      artery or superior mesenteric-portal vein confluence in six patients. Seven
      patients underwent computed tomography-guided fine-needle aspiration; five had
      findings of lymphoma. Two patients underwent distal pancreatectomy and
      splenectomy, and one underwent pancreaticoduodenectomy. All patients were treated
      with combination chemotherapy, and seven received radiotherapy. Only two patients
      have died of disease (12 and 16 months after diagnosis) at a median follow-up
      time of 67 months. CONCLUSIONS: In the majority of patients, pancreatic lymphoma
      can be distinguished from pancreatic adenocarcinoma on the basis of symptoms,
      laboratory and radiographic findings, and fine-needle aspiration biopsy results.
      Once the diagnosis is established, all patients should undergo systemic
      chemotherapy followed by involved-field radiotherapy if the tumor has not been
      resected.

PMID- 9551064
TI  - Diagnosis of anomalous pancreaticobiliary junction: value of magnetic resonance
      cholangiopancreatography.
AB  - BACKGROUND: Anomalous pancreaticobiliary junction (a long common channel), with
      or without congenital choledochal cyst, is frequently associated with biliary
      tract carcinoma. We assessed the diagnostic value of magnetic resonance
      cholangiopancreatography (MRCP) for patients with anomalous pancreaticobiliary
      junction (PBJ). METHODS: In 159 adult patients with pancreatobiliary disease,
      breath-hold (1 to 18 seconds) MRCP was performed according to a half-Fourier
      acquisition single-shot turbo spin-echo sequence. In all patients the length of
      the common channel demonstrated by MRCP was compared with that demonstrated by
      endoscopic retrograde cholangiopancreatography. In 11 patients with anomalous PBJ
      (the common channel > or = 15 mm on endoscopic retrograde
      cholangiopancreatography), the diagnostic accuracy of MRCP for associated biliary
      diseases was evaluated. RESULTS: No complications were encountered in performing
      MRCP. On MRCP, the length of the common channel was calculated to be 15 mm or
      longer in nine (82%) of 11 patients with anomalous PBJ. In patients with normal
      PBJ, MRCP identified PBJ with the channel measuring 0 mm in length. MRCP allowed
      detailed visualization of congenital choledochal cyst (all seven patients) but
      failed to depict carcinoma (one patient) and mucosal hyperplasia (five patients)
      of the gallbladder. CONCLUSIONS: MRCP is a noninvasive and accurate imaging
      method for diagnosing anomalous PBJ and congenital choledochal cyst.

PMID- 9551065
TI  - Growth of intraportally transplanted islets under liver regeneration stimulus and
      restoration of normoglycemia in streptozocin-diabetic rats.
AB  - BACKGROUND: Limitation of beta-cell growth after intraportal islet
      transplantation plays an important role in graft failure. To induce transplanted
      beta-cell proliferation, we studied the effect of compensatory liver growth in
      diabetic rats that had a subtherapeutic islet mass previously injected into the
      liver. METHODS: Syngeneic rats were used as islet donors or recipients; diabetes
      was induced by streptozocin. Three groups of streptozocin-treated rats were
      studied. In group 1, 250 islets were selectively transplanted into the posterior
      liver lobes and 10 days later anterior portal branch ligation (PBL) was performed
      (n = 18); in group 2, 250 islets were transplanted into the posterior lobes and
      10 days later sham PBL was performed (n = 13); in group 3, rats underwent a sham
      transplantation and PBL (n = 6). Nonfasting blood glucose levels and body weight
      were monitored. Six rats in groups 1 and 2 were killed 48 hours after PBL, liver
      sections were stained for proliferating cell nuclear antigen, and islet cell
      labeling index was calculated. The remaining rats were killed 30 days later.
      Liver compensatory growth or atrophy was calculated and morphometric
      determination of beta-cell area was assessed on insulin-immunostained sections of
      the liver. RESULTS: In group 1 rats killed 48 hours after PBL, islet cell
      labeling index was significantly higher than in group 2 (p < 0.0001). After PBL,
      we observed normalization of nonfasting blood glucose levels in 10 of 12 rats. At
      30 days, posterior liver lobes showed compensatory growth (218.5% +/- 18.6%)
      accompanied by atrophy of the anterior lobes; morphometric study of liver
      engrafted islets showed a significant increase of individual beta-cell area,
      compared with group 2 (p < 0.0001). In groups 2 and 3, normoglycemia was not
      achieved. CONCLUSIONS: In streptozocin-diabetic rats, normoglycemia was restored
      after transplantation of a sub-therapeutic islet mass, followed by PBL-induced
      liver regeneration. Histologic and morphometric results indicating islet cell
      proliferation suggest that compensatory liver growth might have induced a
      hypertrophic/hyperplastic response in the intraportally transplanted beta-cells.

PMID- 9551066
TI  - Treatment of hepatoblastoma: less extensive hepatectomy after effective
      preoperative chemotherapy with cisplatin and adriamycin.
AB  - BACKGROUND: Although the prognosis of hepatoblastoma was improved by the
      introduction of cisplatin and doxorubicin (Adriamycin) for adjuvant chemotherapy,
      extensive hepatectomy continues to be the usual practice. We retrospectively
      reviewed our recent experience with hepatoblastoma to determine whether the new
      modality of intensive chemotherapy could change the resectability, extent of
      hepatectomy, operative complications, and prognosis. METHODS: The clinical
      features of 15 children with hepatoblastoma treated between 1985 and 1995 were
      reviewed. Intensive chemotherapy was added before surgical resection not only
      when a tumor was unresectable but also when it was large enough to increase the
      risk of operative morbidity. RESULTS: There was 100% resectability, and the
      overall mortality rate was only 6.7%. Fourteen patients have been free of disease
      for 2 to 12 years. Preoperative chemotherapy enabled resection of six previously
      unresectable hepatoblastomas. Moreover, hepatic resection tended to be less
      invasive in several patients whose tumors had been much reduced after
      preoperative chemotherapy. Intraoperative and postoperative complications were
      minimal, with a short operative time and small amount of blood loss, especially
      in the group with delayed primary operation. CONCLUSIONS: The preoperative
      administration of cisplatin and Adriamycin reduced the tumor size so that a safe
      hepatectomy could be performed with less blood loss and minimal technical
      complications. Unnecessary sacrifice of the normal hepatic tissue was avoided by
      performing the less extensive hepatectomy.

PMID- 9551067
TI  - Hepatic insulin extraction after major hepatectomy.
AB  - BACKGROUND: After major hepatectomy, the remaining liver compensates for its
      reduced mass and maintains euglycemia through increased hepatic glucose output.
      The mechanism of this compensation may be a diminished hepatic extraction of
      portal insulin, which thereby decreases the suppressive effects of insulin on
      gluconeogenesis. METHODS: Extraction of insulin by the liver was measured using
      the isolated perfused rat liver model. Fasted Sprague-Dawley rats were studied at
      1, 2, 3, 4, 6, and 14 days after 70% hepatectomy. Control rats had no operation,
      and sham rats were studied 1 day after a sham laparotomy. The difference between
      portal and caval insulin concentrations was determined and reported as micromoles
      of insulin extracted per gram liver per minute. RESULTS: Insulin extraction
      decreased from 191 +/- 22 microU/gm liver/min in control rats to 87 +/- 13.2
      microU/gm liver/min at postoperative day 1 (p = 0.0001). Extraction normalized by
      postoperative day 6. Extraction rates in rats recovering from sham laparotomy
      were similar to control rats (p = 0.088), suggesting that decreased extraction in
      hepatectomized rats was not due to postoperative stress. CONCLUSIONS: After 70%
      hepatectomy, the remaining liver extracts less insulin per gram. This may explain
      the ability of the reduced liver mass to maintain euglycemia after major
      hepatectomy.

PMID- 9551068
TI  - Hepatolithiasis: outcome of cholangioscopic lithotomy and dilation of bile duct
      stricture.
AB  - BACKGROUND: Cholangioscopic lithotomy (CSL) for hepatolithiasis, a minimally
      invasive procedure, has a place in complicated or recurrent hepatolithiasis. CSL
      itself, however, carries inherent risk for recurrence. We analyzed follow-up data
      after CSL for primary or repeat hepatolithiasis to determine the frequency of
      recurrence. METHODS: This retrospective analysis includes 21 patients with
      hepatolithiasis admitted to the hospital from September 1992 to December 1995 who
      underwent CSL. Through a percutaneous biliary drainage route, cholangioscopy was
      inserted to remove calculi with basket forceps or electrohydraulic lithotripter.
      Stenotic ducts, defined as less than 2 mm in diameter, were dilated with silicone
      rubber stenting or a balloon dilator. RESULTS: Ten patients were treated for
      primary hepatolithiasis and 11 for repeat hepatolithiasis. Of the patients with
      primary hepatolithiasis, one died of complications and the other nine patients
      underwent complete lithotomy. Among 11 patients who had repeat hepatolithiasis,
      four had undergone hepatectomy for hepatolithiasis and two previous CSLs; 10
      patients (91%) underwent complete lithotomy. During the follow-up, four (40%) of
      the 10 patients with biliary stenosis at the time of cholangioscopic treatment
      showed recurrent calculi, whereas all eight patients without stricture had
      uneventful courses. Of the 19 patients who underwent complete lithotomy, calculi
      recurred in four (21%), three cases of which recurred less than 1 year after CSL.
      CONCLUSIONS: Against hepatolithiasis of primary and postoperative repeat cases,
      CSL can allow complete lithotomy. The bile duct stricture, however, carries a
      high risk for recurrent calculi; hence, permanent relief of stricture is
      mandatory.

PMID- 9551069
TI  - Experimental assessment of the risk of tumor recurrence after laparoscopic
      surgery.
AB  - BACKGROUND: The aim of this experimental study was to evaluate the risk of tumor
      recurrence after laparoscopic cecal resection (LCR) of colonic carcinoma in the
      rat. METHODS: The experimental cancer consisted of one million cells (DHK/K12),
      incorporated in an extracellular matrix, placed and secured to the cecal serosa
      in 110 BD9 rats. Four weeks later, all animals were reoperated through a
      laparotomy to control tumor growth, and animals with diffuse carcinomatosis were
      excluded. Eligible animals were randomized either to laparoscopic cecal resection
      (group LCR, n = 10), to open resection (group OCR, n = 13), or to a control group
      without resection (group C, n = 13). Resection was always considered as
      macrocopically complete. All animals were killed 4 weeks after the resection to
      determine the tumor recurrence and quantify carcinomatosis. RESULTS: We noted
      diffuse carcinomatosis in 70% of rats in groups C and LCR versus 23% in group OCR
      (p = 0.038). For tumors noted as S- (not extending outside the serosa), diffuse
      carcinomatosis was observed in all animals of group C (3 of 3), in 6 of 8 in
      group LCR, and 0 of 6 in group OCR (p = 0.004). The rate of port site or
      incisional metastases was not significantly different between groups.
      CONCLUSIONS: These preliminary results demonstrated the deleterious impact of the
      laparoscopy for resection of large bowel malignancy. LCR increased significantly
      the incidence of a diffuse carcinomatosis even when performed for locally
      noninvasive tumors (S-).

PMID- 9551070
TI  - Treatment of superficial cancer of the esophagus: a summary of responses to a
      questionnaire on superficial cancer of the esophagus in Japan.
AB  - BACKGROUND: Histopathologic characteristics and optimal treatment modality for
      superficial esophageal cancer were reevaluated on the basis of 2418 patients from
      143 institutions through a nationwide questionnaire to the members of the
      Japanese Society for Esophageal Diseases. METHODS: A questionnaire was designed
      for patients with preoperatively untreated superficial cancer of the esophagus
      who had undergone either surgical or endoscopic treatment between January 1,
      1990, and December 30, 1994. Mucosal cancer and submucosal cancer were divided
      into three subclasses according to the criteria formulated by the Society.
      RESULTS: The incidence of positive lymphatic invasion or lymph node metastases
      tended to increase markedly as cancer infiltrates reached the lamina muscularis
      mucosa. The majority of the cases with 0-I or 0-III components were submucosal
      cancer. The indication of endoscopic mucosal resection (EMR) was limited to
      mucosal 1 and mucosal 2 superficial cancer in 76% of the institutions surveyed.
      Tumors measuring 2 cm or more in diameter were resected piecemeal in 94% of
      patients. Complications of EMR, including perforation, stenosis, and hemorrhage,
      were observed in approximately 6.8% of patients. Almost all patients with mucosal
      1 or mucosal 2 cancer are still alive. There was no significant difference in
      prognosis between mucosal 3 cancer and mucosal 1 or mucosal 2 cancer, but
      submucosal 1 cancer showed worse prognosis than mucosal cancer. CONCLUSIONS:
      Local resection of cancer lesions is regarded as the treatment of choice against
      the superficial esophageal cancers limited to the lamina propria mucosae. Further
      study is advocated to define the treatment strategy against mucosal 3 or
      submucosal 1 cancer.

PMID- 9551071
TI  - Usefulness of metyrapone treatment to suppress cancer metastasis facilitated by
      surgical stress.
AB  - BACKGROUND: One causative factor of tumor metastasis enhanced by surgical stress
      is thought to be hypersecretion of endogenous glucocorticoids. This study
      evaluated the effectiveness of metyrapone treatment and adrenalectomy in
      preventing the harmful effects of glucocorticoids in the enhancement of tumor
      metastasis resulting from surgical stress. METHODS: The effect of dexamethasone
      on pulmonary metastasis of MRMT-1 cells and on the number of peripheral
      lymphocytes was evaluated in rats. To evaluate the suppressive effect of
      adrenalectomy and metyrapone treatment on operation-induced enhancement of
      metastasis, several parameters such as induction of pulmonary metastasis, serum
      corticosterone levels, and the number of blood lymphocytes and apoptotic
      thymocytes were determined. RESULTS: With dexamethasone treatment, the number of
      peripheral lymphocytes rapidly decreased; in contrast, pulmonary metastasis
      increased. The serum corticosterone level was doubled at 1 hour, apoptotic
      thymocyte numbers were increased about sevenfold at 3 hours and about fourfold at
      6 hours, and blood lymphocyte numbers were decreased at 3 hours after laparotomy,
      which facilitated about a 10-fold increase in the pulmonary metastasis. These
      changes were almost completely suppressed by preoperative adrenalectomy and
      metyrapone treatment. CONCLUSIONS: Preoperative metyrapone treatment, which
      suppresses hypersecretion of endogenous glucocorticoids as a result of operation,
      modulates the enhancement of cancer metastases and may be an effective treatment.

PMID- 9551072
TI  - Less collagen production in smokers.
AB  - BACKGROUND: An association between smoking and impaired wound healing has been
      reported in retrospective studies. The smoking status of a surgical patient may
      be confounded by social and medical parameters. We have evaluated the effect of
      smoking in a test wound in volunteers, with special reference to a reliable
      scientific match between smokers and nonsmokers. METHODS: In a prospective open
      study with blinded assessment, 19 smoking (20 cigarettes/day) and 18 nonsmoking
      healthy volunteers were matched with respect to baseline characteristics. The
      deposition of total protein and mature collagen (expressed as hydroxyproline) was
      assessed in an expanded polytetrafluoroethylene wound healing model implanted
      subcutaneously for 10 days. RESULTS: The nonsmokers had a 1.8 times higher median
      amount of hydroxyproline than the smokers (p < 0.01). The deposition of
      hydroxyproline was negatively correlated with the consumption of tobacco both
      before (r = -0.44; p < 0.01) and during the study (r = -0.48; p < 0.005). The
      impairment was specific for the production of collagenous proteins and not other
      proteins. CONCLUSIONS: The synthesis of subcutaneous collagen in smokers is
      specifically impeded, indicating an impaired wound-healing process. Because
      mature collagen is the main determinator of strength of an operative wound, the
      results support the view that patients should be advised to stop smoking before
      an operation.

PMID- 9551073
TI  - Cyclosporine, but not FK506, selectively induces renal and coronary artery smooth
      muscle contraction.
AB  - BACKGROUND: Cyclosporine immunosuppression for organ transplantation is
      associated with hypertension and nephrotoxicity. Because the effects of
      cyclosporine as an immunosuppressant are mediated by the effect of cyclosporine
      as a phosphatase inhibitor, and phosphatase inhibitors are potent vascular smooth
      muscle contractile agents, we hypothesized that cyclosporine might induce
      contraction of the renal artery vascular smooth muscle directly. METHODS: Strips
      of bovine renal, carotid, superior mesenteric, or coronary arteries were obtained
      fresh from an abattoir. The strips were equilibrated in a muscle bath, and the
      contractile responses to cyclosporine and FK506 were determined. RESULTS:
      Cyclosporine (50 to 5000 micrograms/ml), but not FK506, induced rapidly
      developing, sustained contractions of renal and coronary artery smooth muscle.
      The magnitude of the cyclosporine-induced contractions of carotid and superior
      mesenteric artery smooth muscles was significantly less. The magnitude of renal
      artery smooth muscle contractions induced by cyclosporine was enhanced in the
      presence of an intact endothelium. CONCLUSIONS: Although these effects occurred
      in vitro to relatively high doses of cyclosporine, these data suggest that
      cyclosporine may selectively induce renal artery smooth muscle contraction
      through activation of the Ca(2+)-dependent phosphatase (calcineurin) in the
      smooth muscle, and these contractions may be enhanced by the release of
      endothelial-derived contracting factors.

PMID- 9551074
TI  - Formation of myointimal hyperplasia and cytokine production in experimental vein
      grafts.
AB  - BACKGROUND: The purpose of this study was to determine the correlation between
      progression and regression of myointimal hyperplasia (MH) and cytokine production
      in experimental vein grafts. Although the autologous vein is the best suitable
      bypass conduit for reconstruction of peripheral arteries, at the end of the first
      year thrombosis in the coronary and lower extremity circulation ranges from 20%
      to 50%. Many of these failures are caused by MH. METHODS: In 76 inbred Lewis
      rats, a 1 cm long segment of inferior vena cava was inserted at the level of the
      abdominal aorta. The segments of inferior vena cava were obtained from syngeneic
      Lewis rats. In 56 animals the arterial vein graft was explanted 3 days (n = 10),
      7 days (n = 10), 4 weeks (n = 26), and 12 weeks (n = 10) after operation. In 20
      animals the vein graft was explanted 4 weeks after being in the arterial system
      and reimplanted as iliac venovenous bypass in syngeneic Lewis rats. These grafts
      were explanted 2 weeks (n = 10) and 8 weeks (n = 10) later. Grafts were analyzed
      by light and electron microscopy, morphometric study, and histochemical analysis
      and were put in an organ culture to assess cytokine production. RESULTS: We
      observed MH formation in arterial vein grafts and MH regression in reimplanted
      vein grafts (p < 0.001). MH formation was correlated with production of platelet
      derived growth factor, basic fibroblast growth factor, interleukin-1, and tumor
      necrosis factor-alpha. MH regression was correlated with transforming growth
      factor-beta 1 production. CONCLUSIONS: On the basis of the results of our study,
      we conclude that MH formation in experimental vein grafts depends on production
      of platelet-derived growth factor, basic fibroblast growth factor, interleukin-1,
      and tumor necrosis factor-alpha, and MH regression depends on transforming growth
      factor-beta 1 production. Cytokine therapy may represent a valuable new treatment
      to prevent vein bypass failures caused by MH.

PMID- 9551075
TI  - Duplex-directed vena caval filter placement: report of initial experience.
AB  - BACKGROUND: Fluoroscopy, cost, and patient transport contribute to difficulties
      occasionally associated with the placement of vena caval filters. Follow-up data
      in the literature document the use of duplex ultrasonography in visualizing the
      filter and determining caval patency. Filter placement at the bedside or in the
      vascular laboratory with duplex ultrasonography may simplify this common
      procedure. We have attempted to define the feasibility of this method. METHODS:
      Patients referred to the vascular surgery service for vena caval interruption
      were evaluated for ability to visualize the renal veins and inferior vena cava.
      Location of renal veins, maximum diameter of the vena cava, and presence or
      absence of thrombus were documented. If visualization was adequate, placement was
      performed at the bedside for patients in intensive care or in the vascular
      laboratory for nonmonitored patients. The initial 10 patients and subsequent
      patients in whom there was a question of adequate deployment underwent completion
      abdominal roentgenography. Patient follow-up was difficult. Duplex
      ultrasonography was used to assess migration, thrombus adherent to the filter,
      and vena caval patency. Patients in whom filter placement was prophylactic were
      given anticoagulants at the discretion of the primary physician. Inadequate
      visualization or vena caval size greater than 28 mm prompted fluoroscopic
      placement of the vena caval filter, because only Greenfield titanium filters were
      used in the study. RESULTS: Twenty-nine patients were referred for vena caval
      interruption. Inadequate visualization occurred in four obese patients, and
      filters were placed by fluoroscopy. There were no vena caval measurements greater
      than 24 mm. Twenty-five filters were placed without technical difficulty. One
      filter tilted into the right renal vein, requiring a suprarenal filter placed by
      fluoroscopy. Patient retrieval for follow-up has been difficult, but by
      ultrasonography there has been one vena caval thrombosis and no major filter
      migration. There have been no reported pulmonary emboli other than the one
      patient with initial tilt of the filter. CONCLUSIONS: Placement of vena caval
      filters is feasible with duplex ultrasonography. Visualization is the only
      limiting condition to placement and occurs rarely. Reducing the need for
      fluoroscopy, lowering costs, and not needing to transport the critically ill
      patient support the use of this system. Intravascular ultrasonography in selected
      patients may eliminate the need for fluoroscopic placement of vena caval filters.

PMID- 9551076
TI  - Use of split horseshoe kidney for transplantation.

PMID- 9551077
TI  - Delayed splenic hematoma: an injury in evolution.

PMID- 9551078
TI  - A case of axillary arterial bleeding caused by radiation-induced chest wall ulcer
      after radiotherapy for carcinoma of the breast: extraanatomic bypass grafting for
      upper limb salvage.

PMID- 9551079
TI  - Autogenous patching of a kinked internal carotid artery.

PMID- 9551080
TI  - Negative influence of RasG on chemoattractant-induced ERK2 phosphorylation in
      Dictyostelium.
AB  - The Dictyostelium ERK2 protein is transiently activated when cells are treated
      with the chemotactic agents cAMP or folic acid. Activating phosphorylation is
      markedly inhibited in strains overexpressing the constitutively activated RasG
      protein. This is in marked contrast to mammalian cells where the highly related
      mitogen-activated protein kinases (MAPKs) are stimulated by Ras activation.

PMID- 9551081
TI  - Studies of perinuclear and nuclear translocation of the Raf-1 protein in rodent
      fibroblasts.
AB  - Raf-1, A-Raf and B-Raf comprise a small family of highly conserved
      serine/threonine protein kinases, whose activities play a fundamental role in the
      control of proliferation and differentiation. The best studied family member, Raf
      1, is expressed ubiquitously and constitutively, and its activity is regulated by
      post-translational mechanisms. Raf-1 can be activated by many signals that
      include growth factors, tumor promoters, inflammatory cytokines, calcium
      mobilization, DNA damaging agents, and oxygen radicals. Ras-mediated
      translocation of Raf-1 to the plasma membrane is a crucial step in its activation
      process, and is thought to facilitate phosphorylation by membrane-bound kinases.
      Raf-1 has also been reported to undergo intracellular redistribution following
      its activation: to the perinuclear space in murine NIH3T3 cells and rat hepatic
      Ito cells, and into the nucleus in gerbil hippocampal pyramidal cells and human
      MO7 leukemia cells. In contrast to the translocation to the plasma membrane, the
      perinuclear and/or nuclear translocation of Raf-1 has not been investigated in
      detail. In this paper, we report an examination of the subcellular localization
      of endogenous Raf-1 in a fibroblastic cell line (Rat-1) commonly used in
      transformation assays. Using the methods of cellular fractionation as well as in
      situ immunofluorescence, we show that no detectable movement of Raf-1 to the
      perinuclear or nuclear space can be observed. Tethering of activated Raf to the
      plasma membrane does not interfere with its transforming activity.

PMID- 9551082
TI  - Constitutive and interferon-gamma-induced expression of the human proteasome
      subunit multicatalytic endopeptidase complex-like 1.
AB  - Proteasomes generate peptides from intracellular endogenous and viral proteins
      for presentation by MHC class I molecules. During viral infection, interferon
      gamma (IFN-gamma) acts as a cytokine altering the catalytic specificity of
      proteasomes by inducing the synthesis of the three proteasome subunits, low
      molecular weight protein (LMP) 2, LMP7 and multicatalytic endopeptidase complex
      like 1 (MECL1). LMP2 and LMP7 have been shown to favour the presentation of
      certain antigenic peptides. These subunits are constitutively expressed in cell
      lines related to the immune system and IFN-gamma-inducible in other cell lines.
      Less is known about MECL1. To reveal the extent of constitutive and IFN-gamma
      induced expression of MECL1, we studied MECL1 in different cell lines by Northern
      and Western blotting. The two B cell lines IM9 and Reh showed high constitutive
      expression of MECL1, only slightly induced by IFN-gamma stimulation. The B cell
      line Daudi and the monocyte cell line THP-1 expressed MECL1 constitutively at an
      intermediate level. The MECL1 protein level in the THP-1 cells increased markedly
      in response to IFN-gamma. In cells unrelated to the immune system, a very low
      constitutive expression of MECL1 was detected, highly inducible by IFN-gamma.
      These results indicate that, similar to LMP2 and LMP7, MECL1 is constitutively
      expressed at high levels only in certain cell lines and can be induced by IFN
      gamma in other cell lines. The differential expression of MECL1 may be of
      importance for which antigenic peptides are presented by different cells as well
      as by the same cells at different IFN-gamma levels.

PMID- 9551084
TI  - Hepatocyte growth factor plays a dual role in regulating skeletal muscle
      satellite cell proliferation and differentiation.
AB  - The role of hepatocyte growth factor (HGF) and its receptor, c-met, in
      proliferation and differentiation of satellite cells was studied in primary
      cultures of chicken skeletal muscle satellite cells and a myogenic C2 cell line.
      HGF mRNA was expressed mainly in the myotubes of both cultures. The addition of
      conditioned medium derived from those cultures had a scattering effect on the
      canine kidney epithelial cell line, MDCK. In contrast, c-met mRNA levels
      decreased during cell differentiation of C2 and primary satellite cells.
      Application of exogenous HGF to chicken myoblasts resulted in their enhanced DNA
      synthesis. Among several growth factors, HGF was the first to induce DNA
      synthesis in quiescent satellite cells, thereby driving them into the cell cycle.
      Ectopic expression of chicken HGF in primary satellite cells suppressed the
      activation of muscle-regulatory gene reporter constructs MCK-CAT, MRF4-CAT, MEF2
      CAT and 4Rtk-CAT, as well as the gene expression of MyoD and myogenin, and MHC
      protein expression. Ectopic MyoD reversed HGF's inhibitory effect on MCK
      transactivation. These data suggest that HGF inhibits cell differentiation by
      inhibiting the activity of basic helix-loop-helix (bHLH)/E protein heterodimers,
      thus inhibiting myogenic determination factor activity and subsequent muscle
      specific protein expression. During muscle growth and regeneration, HGF plays a
      dual role in satellite-cell myogenesis, affecting both the proliferation and
      differentiation of these cells in a paracrine fashion.

PMID- 9551083
TI  - Selection and characterisation of murine leukaemia L1210 cells with high-level
      resistance to the cytostatic activity of the acyclic nucleoside phosphonate 9-(2
      phosphonylmethoxyethyl) adenine (PMEA).
AB  - An L1210 cell line showing a 300-fold resistance to the cytostatic effect of 9-(2
      phosphonylmethoxyethyl)adenine (PMEA) (designated L1210/PMEA-1) was selected in
      cell culture upon exposure of wild-type L1210/0 cells to stepwise-increased drug
      concentrations. The mutant L1210/PMEA-1 cell line was characterized by an unusual
      specificity in that the cytostatic activity was severely impaired only for PMEA
      and the closely related 2,6-diaminopurine derivative PMEDAP, but not for its
      guanine counterpart PMEG or for 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine
      (HPMPA). The L1210/PMEA-1 cell line showed poor resistance to the cytostatic
      activity of the lipophilic PMEA prodrug bis(POM)PMEA and virtually kept its PMEA
      resistance profile in the presence of indomethacin, excluding resistance of the
      cells of PMEA and PMEDAP by an increased efflux of the drugs. Intracellular
      purine nucleotide pool labelling studies with adenine, hypoxanthine and glycine
      revealed that PMEA/PMEDAP resistance did not originate from a defect in the
      enzymatic pathways of purine nucleotides. ATP, AMP and cAMP, but not adenosine,
      adenine, HPMPA and inhibitors of nucleoside transport carriers markedly
      interfered with PMEA uptake in L1210/0 cells. The L1210/PMEA-1 cells proved to
      have less than 10% of the PMEA uptake capacity of wild-type L1210/0 cells as
      measured by rapid sampling kinetics as well as long-term incubation experiments.
      After a 24-h incubation period, the intracellular levels of [2,8-3H]PMEA and its
      phosphorylated metabolites were approximately 10-fold lower in L1210/PMEA-1 cells
      than in L1210/0 cells. Our observations point to a compromised and highly
      specific PMEA/PMEDAP uptake as the molecular basis for the pronounced PMEA
      resistance of the mutant L1210/PMEA-1 cells.

PMID- 9551085
TI  - The calpain-calpastatin system and protein degradation in fusing myoblasts.
AB  - Calpain (Ca(2+)-activated cysteine protease) induced proteolysis has been
      suggested to play a role in myoblast fusion. We previously found that calpastatin
      (the endogenous inhibitor of calpain) diminishes markedly in myoblasts during
      myoblast differentiation just prior to the start of fusion, allowing Ca(2+)
      induced calpain activation at that stage. Here, we show that a limited
      degradation of some proteins occurs within the myoblasts undergoing fusion, but
      not in proliferating myoblasts. The protein degradation is observed at the stage
      when calpastatin is low. Protein degradation within the myoblasts and myoblast
      fusion are inhibited by EGTA, by the cysteine protease inhibitors calpeptin and E
      64d and by calpastatin. The degradation appears to be selective for certain
      myoblast proteins. Integrin beta 1 subunit, talin and beta-tropomyosin are
      degraded in the fusing myoblasts, whereas alpha-actinin, beta-tubulin and alpha
      tropomyosin are not. A similar pattern of degradation is observed in lysates of
      proliferating myoblasts when Ca2+ and excess calpain are added, a degradation
      that is inhibited by calpastatin. The results support the notion that degradation
      of certain proteins is required for myoblast fusion and that calpain participates
      in the fusion-associated protein degradation. Participation of calpain is made
      possible by a change in calpain/calpastatin ratio, i.e., by a diminution in
      calpastatin level from a high level in the proliferating myoblasts to a low level
      in the differentiating myoblasts. Degradation of certain proteins, known to be
      responsible for the stability of the membrane-skeleton organization and for the
      interaction of the cell with the extracellular matrix, would allow
      destabilization of the membrane and the creation of membrane fusion-potent
      regions.

PMID- 9551086
TI  - Evidence that photodynamic stress kills Zellweger fibroblasts by a nonapoptotic
      mechanism.
AB  - Zellweger fibroblasts, which are devoid of peroxisomes and fail to synthesize
      plasmalogens, are very sensitive to the killing effect triggered by UV-activated
      12-(1-pyrene) dodecanoic acid (P12). Although in some studied performed, it is
      assumed that reactive oxygen species (ROS) may damage plasma membrane causing
      necrosis, other studies suggest that ROS are involved in apoptotic cell death
      induced by a wide variety of stimuli. Analysing the P12 dose-response in
      Zellweger fibroblasts, we observed that at high doses (1-2 microM), more than 75%
      of the cells died after 24 h. This behaviour suggested that, at high doses, P12
      kills the cells by unspecific lytic mechanisms or by necrosis, while at low doses
      (0.1-0.5 microM), an apoptotic mechanism could be involved. Cytofluorimetric
      analysis of Zellweger fibroblasts-treated with activated P12 (0.5 microM) did not
      show morphological modifications typical of apoptotic cell death. This was
      supported by comparative staining of fibroblast nuclei, DNA gel electrophoresis
      and identification of poly(ADP-ribose) polymerase (PARP) cleavage and Bcl-2
      expression, assayed by Western blots. Thus, our results, while confirming the
      importance of plasmalogens in the protection against ROS, establish that
      apoptosis is not involved in photodynamic death induced by activated P12.
      Therefore, we can expect that in gene transfer experiments, the rescue of
      Zellweger cells will be dependent only on the correction of peroxisomal
      biogenesis.

PMID- 9551087
TI  - A novel Arabidopsis thaliana protein protects tumor cells from tumor necrosis
      factor-induced apoptosis.
AB  - Recently we have cloned and characterized a novel, oxidative stress-induced
      Arabidopsis thaliana gene (oxy5), and showed that expression of oxy5 protects
      bacterial cells from death caused by oxidative stress. As oxidative stress is one
      pathway of TNF cytotoxicity, we investigated whether the encoded protein could
      also protect human tumor cells from TNF killing. We stably transfected the oxy5
      gene into TNF-sensitive HeLa D98 cells (D98/O.5), and found that all examined
      transfectants were highly TNF-resistant in the absence of the protein synthesis
      inhibitor cycloheximide. The acquired TNF resistance of these clones was
      accompanied by a sharp decrease in the intracellular formation of reactive oxygen
      species, suggesting the activation of antioxidant enzymes like superoxide
      dismutases (SODs). Indeed, D98/O.5 clones showed an increased manganous
      superoxide dismutase (MnSOD) mRNA and protein expression in the absence or
      presence of TNF stimulation, whereas the expression of the Cu/ZnSOD was not
      affected. Furthermore, the elevated MnSOD expression in the D98/O.5 clones
      correlated well with an increased antioxidative activity, which was specifically
      due to MnSOD as measured by the suppression of xanthine oxidase. Our results
      demonstrate a novel role for a plant-derived protein in resistance to TNF
      cytotoxicity, and that the Arabidopsis thaliana protein Oxy5 can exert its
      protective function across evolutionary boundaries through activation of
      antioxidant enzymes like MnSOD.

PMID- 9551088
TI  - Induction of the DNA-binding and transcriptional activities of heat shock factor
      1 is uncoupled in Xenopus oocytes.
AB  - The DNA-binding and transcriptional activities of the heat shock transcription
      factor 1 (HSF1) are repressed under normal conditions and rapidly upregulated by
      heat stress. Here, we tested for the ability of various stress agents to activate
      HSF1 in the Xenopus oocyte model system. The HSE-binding activity of HSF1 was
      induced by a number of chemical stresses including cadmium, aluminum, iron,
      mercury, arsenite, ethanol, methanol, and salicylate. HSE-binding was not induced
      by several stresses known to induce the synthesis of hsps in other cell types in
      different organisms including zinc, copper, cobalt, manganese, recovery from
      anoxia, UV-irradiation, and increased pH. The inability of several known inducers
      of the stress response to activate the HSE-binding ability of HSF1 suggests that
      certain stress activation pathways may be absent or inactive in oocytes. The
      transcriptional activity of oocyte HSF1 was induced by heat, cadmium, and
      arsenite, but many of the agents that induced HSE-binding failed to stimulate
      HSF1-mediated transcription. The apparent uncoupling of inducible HSE-binding and
      transcriptional activities of HSF1 under a variety of stress regimes indicates
      that these events are regulated by independent mechanisms in the oocyte.

PMID- 9551089
TI  - Role of arginine 86 of the insulin receptor in insulin binding and activation of
      glucose transport.
AB  - Mutations in the insulin receptor gene cause the inherited insulin resistant
      syndrome leprechaunism. Patient Atl-1 with leprechaunism was homozygous for the
      substitution of Arg-86 with Pro (R86P) in the alpha subunit of the insulin
      receptor. Fibroblasts homozygous for the mutant receptor had defective insulin
      binding, but increased glucose transport and receptor kinase activity. The R86P
      mutation is located in a putative beta turn N-terminal to a proposed insulin
      binding domain of the receptor [P. DeMeyts, J.L. Gu, R.M. Shymko, B.E. Kaplan,
      G.I. Bell, J. Whittaker, Mol. Endocrinol. 4 (1990) 409-416]. To get further
      insight into the mechanism of the paradoxical activation of receptor signalling
      by the R86P mutation, the codons for proline, alanine, and glycine were
      substituted in the R86 position of the insulin receptor cDNA by PCR-mediated
      mutagenesis and stably transfected into Chinese hamster ovary (CHO) cells.
      Insulin binding increased 10-20 fold in CHO cells transfected with the wild type,
      the R86A, and the R86G insulin receptor cDNA, but did not increase in cells
      expressing the R86P mutation. The R86P mutation caused a constitutive activation
      of insulin receptor phosphorylation in CHO cells, but did not increase basal
      glucose transport or its sensitivity to insulin stimulation. By contrast,
      transfection with the wild type and the R86A receptors increased 20-30 fold the
      sensitivity of glucose transport to stimulation by insulin. The R86G insulin
      receptor bound insulin normally, but was four times less efficient than the wild
      type or R86A insulin receptor in increasing the sensitivity for insulin
      stimulation of glucose transport. These results indicate that position 86 of the
      insulin receptor alpha subunit is tolerant to substitution by alanine, but not by
      proline. Substitution with glycine allows insulin binding, but does not activate
      normally glucose transport, further supporting an essential role of this position
      in the initiation of insulin receptor signalling of glucose transport.

PMID- 9551091
TI  - cGMP potentiates receptor-stimulated Ca2+ influx in Dictyostelium discoideum.
AB  - Binding of extracellular cAMP to surface receptors induces at least two responses
      in Dictyostelium discoideum, the G-protein-dependent activation of guanylyl
      cyclase, and the opening of a plasma membrane Ca2+ channel. Some experiments
      suggest that intracellular cGMP opens the Ca2+ channel, while others demonstrate
      that the channel can open in the absence of functional G-proteins (and thus in
      the absence of cGMP formation). We have analysed 45Ca2+ uptake in three mutants
      with altered cGMP formation. Mutant stmF shows a prolonged cGMP response due to
      deletion of an intracellular phosphodiesterase. Uptake of receptor-stimulated
      45Ca2+ is enhanced about two-fold in this mutant if compared to wild-type cells,
      suggesting that cGMP regulates the opening of the channel. Mutant KI-7 has very
      low levels of surface cAMP receptors, but nevertheless an enhanced receptor
      stimulated cGMP response due to a defect in the turn-off of guanylyl cyclase.
      This mutant shows poor receptor-stimulated 45Ca2+ uptake, suggesting that cGMP
      alone is not sufficient to open the Ca2+ channel. Finally, mutant KI-8 has no
      cGMP due to the absence of nearly all guanylyl cyclase activity. The mutant shows
      significant but reduced 45Ca2+ uptake (19% of wild-type; 60% if corrected for the
      reduced level of surface cAMP receptors), suggesting that the channel can open in
      the absence of cGMP. Taken together, the results demonstrate that receptor
      stimulated Ca2+ influx is not directly induced by cGMP formation; it can occur in
      the absence of cGMP, but is potentiated two- to four-fold by cGMP.

PMID- 9551092
TI  - The mechanism of Ca2+ release from the SR of permeabilised guinea-pig and rat
      ureteric smooth muscle.
AB  - Recent work has indicated that there is a major difference in the Ca2+ store of
      smooth muscle from rat and guinea-pig ureter; with the rat store being agonist
      sensitive but ryanodine insensitive and the guinea-pig store being ryanodine
      sensitive but agonist insensitive [Th. V. Burdyga, M.J. Taggart, S. Wray, J.
      Physiol. 489 (1995) 327-335]. We have therefore examined directly the mechanism
      of Ca2+ release from the internal Ca2+ store (SR). Following permeabilisation
      with alpha-toxin or beta-escin the SR was Ca(2+)-loaded before application of
      carbachol or caffeine. Only carbachol evoked a transient contraction in rat
      ureter. The carbachol-induced contraction was blocked by heparin and
      cyclopiazonic acid (CPA) but not ryanodine. Only caffeine produced contraction in
      guinea-pig ureter, and this was blocked by ryanodine. Direct application of IP3
      caused a small transient contraction in rat but not guinea-pig ureter. We
      conclude that rat ureter possesses only an IP3 sensitive store while guinea-pig
      ureter only has a ryanodine sensitive store.

PMID- 9551090
TI  - Phosducin-like protein (PhLP), a regulator of G beta gamma function, interacts
      with the proteasomal protein SUG1.
AB  - Phosducin-like protein (PhLP) and phosducin are highly homologous proteins that
      interact with the beta gamma subunits of guanine nucleotide binding proteins.
      While phosducin has a well-characterized role in retinal signal transduction,
      PhLP function remains unclear. To further understand the function of PhLP, we
      have examined other potential protein:protein interactions with PhLP using the
      yeast two-hybrid system. PhLP was found to interact with a mouse homologue of the
      yeast SUG1, a subunit of the 26S proteasome which may also indirectly modulate
      transcription. This interaction was further confirmed by an in vitro binding
      assay and co-immunoprecipitation of the two proteins in overexpression studies.
      Inhibition of proteasome function by lactacystin led to accumulation of high
      molecular weight, ubiquitin-immunoreactive protein precipitated by PhLP
      antiserum. We suggest that PhLP/SUG1 interaction may target PhLP for proteasomal
      degradation.

PMID- 9551093
TI  - [Result of antineoplastic agents screening: 7th report].

PMID- 9551094
TI  - The DNA binding specificity of engrailed homeodomain.
AB  - The engrailed gene of Drosophila melanogaster is an integral member of the highly
      complex cascade which results in a fully developed fruitfly. The gene product of
      engrailed contains a homeodomain which is responsible for DNA binding via a helix
      turn-helix motif. The crystal structure of this 60 amino acid residue domain
      complexed to DNA is analogous to structures of other homeodomain-DNA complexes,
      consistent with the high degree of sequence conservation within both protein and
      DNA. Despite the high degree of homology, homeodomains do exhibit distinct
      preferences for certain DNA sequences. Such specificity may be at least partly
      responsible for the interactions necessary for normal development. Using the
      hydroxyl radical as a chemical probe, we have examined complexes of Engrailed
      homeodomain with several DNA sequences to determine the protein's binding
      specificity in solution. We find that Engrailed forms a single, specific complex
      with a unique DNA binding site which is analogous to the complex seen in the co
      crystal structure. In contrast, our chemical probe experiments show that the
      binding site of Engrailed that was determined by in vitro selection and that also
      was present in the co-crystal structure contains two possible binding sites.
      Modification of the sequence of this site to yield single binding sites removes
      the ambiguity, and results in two different, well-behaved Engrailed-DNA
      complexes. Our results underscore the utility of chemical probe experiments for
      defining the variety of modes of interaction of proteins with DNA that can occur
      in solution, but that might not be apparent in a crystal structure.

PMID- 9551095
TI  - Base-pairing of 23 S rRNA ends is essential for ribosomal large subunit assembly.
AB  - In ribosomal RNA precursors the spacer sequences bracketing mature 16 S and 23 S
      rRNA are base-paired to form long helices (processing stems). In pre-23 S rRNA,
      the processing stem is continued by eight base-pairs of mature 23 S rRNA known as
      helix 1. Recently, we have found that any part of 23 S rRNA between positions 40
      and 2773 could be deleted without the loss of ribosome-like particle formation,
      while both end regions were indispensable. In this paper we have analyzed the
      role of the 5' and 3' end regions of 23 S rRNA during ribosomal 50 S assembly in
      vivo by using mutants of the 23 S rRNA gene. Deletions and substitutions in both
      strands of the helix 1 lead to the loss of plasmid derived 50 S formation.
      Compensatory mutations restoring helix 1 were assembled into functional 50 S
      subunits. We conclude that the helix 1 of 23 S rRNA is the main RNA determinant
      for ribosomal large-subunit assembly. Deletions in both the 5' and 3' strand of
      the processing stem reduced the ability of the 23 S rRNA to form ribosomal 50 S
      subunits. However, even the complete removal of either the 5' or the 3' strand of
      the processing stem did not abolish the 50 S assembly completely. Thus,
      processing stem facilitates, but is not essential for assembly.

PMID- 9551096
TI  - Mutations in the leader region of ribosomal RNA operons cause structurally
      defective 30 S ribosomes as revealed by in vivo structural probing.
AB  - The biogenesis of functional ribosomes is regulated in a very complex manner,
      involving different proteins and RNA molecules. RNAs are not only essential
      components of both ribosomal subunits but also transiently interacting factors
      during particle formation. In eukaryotes snoRNAs act as molecular chaperones to
      assist maturation, modification and assembly. In a very similar way highly
      conserved leader sequences of bacterial rRNA operons are involved in the correct
      formation of 30 S ribosomal subunits. Certain mutations in the rRNA leader region
      cause severe growth defects due to malfunction of ribosomes which are assembled
      from such transcription units. To understand how the leader sequences act to
      facilitate the formation of the correct 30 S subunits we performed in vivo
      chemical probing to assess structural differences between ribosomes assembled
      either from rRNA transcribed from wild-type operons or from operons which contain
      mutations in the rRNA leader region. Cells transformed with plasmids containing
      the respective rRNA operons were reacted with dimethylsulphate (DMS). Ribosomes
      were isolated by sucrose gradient centrifugation and modified nucleotides within
      the 16 S rRNA were identified by primer extension reaction. Structural
      differences between ribosomes from wild-type and mutant rRNA operons occur in
      several clusters within the 16 S rRNA secondary structure. The most prominent
      differences are located in the central domain including the universally conserved
      pseudoknot structure which connects the 5', the central and the 3' domain of 16 S
      rRNA. Two other clusters with structural differences fall in the 5' domain where
      the leader had been shown to interact with mature 16 S rRNA and within the
      ribosomal protein S4 binding site. The other differences in structure are located
      in sites which are also known as sites for the action of several antibiotics. The
      data explain the functional defects of ribosomes from rRNA operons with leader
      mutations and help to understand the altered biogenesis pathway from mutations in
      an rRNA leader region to the formation of functionally defective ribosomes.

PMID- 9551097
TI  - Slipped misalignment mechanisms of deletion formation: analysis of deletion
      endpoints.
AB  - To gain insight into the mechanisms of deletion formation between tandem repeats,
      Escherichia coli plasmids were engineered to carry a 101 bp tandem duplication
      within the tetA gene such that deletion of one of the repeats restores an intact
      tetA gene and tetracycline resistance to the cell. Four base-pair changes were
      introduced into one of the tandem repeats to serve as genetic markers. After
      selection for deletion, individual plasmid products were sequenced to deduce
      where within the repeat the deletion had occurred. Our analysis shows most
      deletions are fusions of the two repeats in a single 20 bp interval. This is
      consistent with the simple replication slip-pair model for deletion formation and
      suggests that this interval may have unusual features that promote deletion.
      Dimer replicon products have experienced a sister-chromosome exchange event in
      addition to deletion and carry two tetA loci: a deleted locus showing a similar
      distribution of endpoints as seen-in the monomer products and an unchanged repeat
      locus. Seemingly reciprocal dimers are occasionally recovered which carry both a
      deleted and a triplicated tetA locus. These are not truly reciprocal in that the
      sequence analysis showed that the deletion and triplication had occurred in
      separate intervals. Sequence analysis of the dimeric products is consistent with
      predictions from our sister-strand exchange model where slipped alignment of
      nascent DNA strands induces deletion formation concomitant with sister-chromosome
      exchange.

PMID- 9551098
TI  - Thermodynamics of specific and non-specific DNA binding by the c-Myb DNA-binding
      domain.
AB  - The thermodynamics of the c-Myb DNA-binding domain (R2R3) interaction with its
      target DNA have been analyzed using isothermal titration calorimetry and amino
      acid mutagenesis. The enthalpy of association between the standard R2R3, the
      Cys130 mutant substituted with Ile, and the cognate DNA is -12.5 (+/- 0.1) kcal
      mol-1 at pH 7.5 and at 20 degrees C, and this interaction is enthalpically driven
      throughout the physiological temperature range. In order to understand the DNA
      recognition mechanism, several pairs of interactions were investigated using
      single and multiple-base alterations with single and multiple-amino acid
      substituted mutants. The interactions between the standard R2R3 and many non
      cognate DNAs were accompanied by binding enthalpy changes and heat capacity
      changes, although their affinities were reduced. The roles of the electrostatic
      interactions in binding to the cognate and the non-cognate DNAs were also
      analyzed from the dependency of the thermodynamic parameters on the salt
      concentration. The heat capacity change was found to be significantly dependent
      upon the salt concentration. Several mutant proteins bound to the multiple-base
      altered DNA with very small enthalpy changes, although they bound to the cognate
      and the single-base altered DNAs with detectable enthalpy and heat capacity
      changes. From the thermodynamic cycles derived from the DNA binding of the amino
      acid substituted R2R3 to the base substituted DNA duplexes, the individual
      thermodynamic mechanisms of the specific DNA recognition of R2R3 were dissected.
      The local folding mechanism was highlighted by the substitution of Pro with
      either Gly or Ala at the linker between R2 and R3. The characteristic
      thermodynamic features of specific and non-specific DNA binding are discussed.

PMID- 9551099
TI  - Crystal structure of the IIB subunit of a fructose permease (IIBLev) from
      Bacillus subtilis.
AB  - The bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS)
      mediates both the uptake of carbohydrates across the cytoplasmic membrane and
      their phosphorylation. During this process, a phosphoryl group is transferred
      from phosphoenolpyruvate via the general PTS proteins enzyme I, HPr and the sugar
      specific components IIA, IIB to the transported sugar. The crystal structure of
      the IIB subunit of a fructose transporter from Bacillus subtilis (IIBLev) was
      solved by MIRAS to a resolution of 2.9 A. IIBLev comprises 163 amino acid
      residues that are folded into an open, mainly parallel beta-sheet with helices
      packed on either face. The phosphorylation site (His15) is located on the first
      loop (1/A) at one of the topological switch-points of the fold. Despite different
      global folds, IIBLev and HPr have very similar active-site loop conformations
      with the active-site histidine residues located close to the N terminus of the
      first helix. This resemblance may be of functional importance, since both
      proteins exchange a phosphoryl group with the same IIA subunit. The structural
      basis of phosphoryl transfer from HPr to IIAMan to IIBMan was investigated by
      modeling of the respective transition state complexes using the known HPr and
      IIAMan structures and a homology model of IIBMan that was derived from the IIBLev
      structure. All three proteins contain a helix that appears to be suitable for
      stabilization of the phospho-histidine by dipole and H-bonding interactions.
      Smooth phosphoryl transfer from one N-cap position to the other appears feasible
      with a minimized transition state energy due to simultaneous interactions with
      the donor and the acceptor helix.

PMID- 9551100
TI  - Crystal structure of tryptophanase.
AB  - The X-ray structure of tryptophanase (Tnase) reveals the interactions responsible
      for binding of the pyridoxal 5'-phosphate (PLP) and atomic details of the K+
      binding site essential for catalysis. The structure of holo Tnase from Proteus
      vulgaris (space group P2(1)2(1)2(1) with a = 115.0 A, b = 118.2 A, c = 153.7 A)
      has been determined at 2.1 A resolution by molecular replacement using tyrosine
      phenol-lyase (TPL) coordinates. The final model of Tnase, refined to an R-factor
      of 18.7%, (Rfree = 22.8%) suggests that the PLP-enzyme from observed in the
      structure is a ketoenamine. PLP is bound in a cleft formed by both the small and
      large domains of one subunit and the large domain of the adjacent subunit in the
      so-called "catalytic" dimer. The K+ cations are located on the interface of the
      subunits in the dimer. The structure of the catalytic dimer and mode of PLP
      binding in Tnase resemble those found in aspartate amino-transferase, TPL, omega
      amino acid pyruvate aminotransferase, dialkylglycine decarboxylase (DGD),
      cystathionine beta-lyase and ornithine decarboxylase. No structural similarity
      has been detected between Tnase and the beta 2 dimer of tryptophan synthase which
      catalyses the same beta-replacement reaction. The single monovalent cation
      binding site of Tnase is similar to that of TPL, but differs from either of those
      in DGD.

PMID- 9551101
TI  - Folding intermediates of wild-type and mutants of barnase. I. Use of phi-value
      analysis and m-values to probe the cooperative nature of the folding pre
      equilibrium.
AB  - It is difficult to determine whether transient folding intermediates have a
      cooperative (or first-order) folding transition without measuring their rates of
      formation directly. An intermediate I could be formed by a second-order
      transition from a denatured state D that is progressively changed into I as
      conditions are changed. We have not been able to monitor the rate of formation of
      the folding intermediate of barnase directly, but have analysed its reactivity
      and the equilibrium constant for its formation over a combination of wide ranges
      of temperature, concentration of denaturant and structural variation. Phase
      diagrams have been constructed for wild-type and 16 mutant proteins to map out
      the nature of the energy landscape of the denatured state. The free energy of
      unfolding of I, delta GD-I, changes with [urea] according to a highly cooperative
      transition. Further, mD-I (= delta delta GD-I/delta [urea]) for wild-type and
      several mutants is relatively insensitive to temperature, as would be expected
      for an intermediate that is formed cooperatively, rather than one that melts out
      according to a second-order transition. The phi-values for the formation of I
      change abruptly through the folding transitions rather than have the smooth
      changes expected for a second-order transition. There is a subset of mutants for
      which both mD-I and phi-value analysis indicate that a second intermediate
      becomes populated close to the melting temperatures of the native proteins. The
      folding intermediate of barnase is, thus, a relatively discrete and compact
      entity which is formed cooperatively.

PMID- 9551102
TI  - Folding intermediates of wild-type and mutants of barnase. II. Correlation of
      changes in equilibrium amide exchange kinetics with the population of the folding
      intermediate.
AB  - There is an unanswered question from previous studies of 1H/2H-exchange of amide
      protons of barnase. Under certain conditions, there is a relatively abrupt change
      from EX2 towards EX1 kinetics as the temperature is slightly increased. The
      change in kinetics for different mutants is not directly related to their changes
      in stability. We have measured the stability of the folding intermediate of
      barnase (I) in 2H2O under a variety of conditions and calculated its population
      at different temperatures. The change in kinetics correlates with the change in
      the population of the folding intermediate. At higher temperatures and pH, the
      free energy of I becomes higher than that of the denatured state, D, and the
      kinetics becomes EX1. The data fit a simple kinetic scheme. Such changes in
      kinetics may be used to detect the presence of intermediates in the folding
      reaction at equilibrium in native conditions, but cannot distinguish whether they
      are on or off-pathway.

PMID- 9551103
TI  - Folding kinetics of the SH3 domain of PI3 kinase by real-time NMR combined with
      optical spectroscopy.
AB  - The refolding kinetics of the chemically denatured SH3 domain of
      phosphatidylinositol 3'-kinase (PI3-SH3) have been monitored by real-time one
      dimensional 1H NMR coupled with a variety of other biophysical techniques. These
      experiments indicate that the refolding kinetics of PI3-SH3 are biphasic. The
      slow phase (27 (+/- 8)% amplitude) is due to a population of substantially
      unfolded molecules with an incorrectly configured cis proline residue. The fast
      phase (73 (+/- 8)% amplitude) corresponds to the folding of protein molecules
      with proline residues in a trans configuration in the unfolded state. NMR
      experiments indicate that the first species populated after the initiation of
      folding exhibit poor chemical shift dispersion and have spectra very similar to
      that of the denatured protein in 8 M guanidine hydrochloride. Linear combinations
      of the first spectrum and of the spectrum of the native protein accurately
      reconstruct all of the spectra acquired during refolding. Consistent with this,
      native side-chain and backbone H alpha atom packing (NMR), secondary structure
      (far-UV circular dichroism), burial of aromatic residues (near-UV circular
      dichroism), intrinsic fluorescence and peptide binding activity are all recovered
      with effectively identical kinetics. Equilibrium unfolding and folding/unfolding
      kinetics yield, within experimental error, identical values for the free energy
      of unfolding (delta Gu-H2O = 3.38 kcal mol-1) and for the slope of the free
      energy of unfolding versus denaturant concentration (meq = 2.33 kcal mol-1 M-1).
      Together, these data provide strong evidence that PI3-SH3 folds without
      significant population of kinetic well-structured intermediates. That PI3-SH3
      folds slowly (time constant 2.8 seconds in H2O at 20 degrees C) indicates that
      slow refolding is not always a consequence of kinetic traps but may be observed
      even when a protein appears to fold via a simple, two-state mechanism.

PMID- 9551104
TI  - Equilibrium folding intermediates of a Greek key beta-barrel protein.
AB  - Protein S is a calcium-binding protein comprising two Greek key beta-barrel
      domains. We have used NMR and optical spectroscopies to show that, in the absence
      of calcium, the N-terminal domain of protein S forms two equilibrium folding
      intermediates that are in slow exchange. The intermediates arise from
      differential calcium-dependent folding of subdomains which are not contiguous
      along the polypeptide chain. The structures of these intermediates are
      incompatible with several previously proposed folding mechanisms for Greek key
      beta-barrel domains. We proposed a different mechanism that involves multiple
      nucleation sites for folding and sequential acquisition of native long-range
      interactions.

PMID- 9551105
TI  - [Value of dual-phase-helical CT in the preoperative diagnosis of pancreatic
      cancer--a prospective study].
AB  - PURPOSE: A prospective study was performed to evaluate the accuracy of dual phase
      helical CT in suspected pancreatic cancer. METHODS: Within one year 136 patients
      underwent helical CT with arterial and portal venous scans after bolus tracking
      and NaCl bolus injection. Evidence of pancreatic cancer and assessment of
      resectability were recorded using a standardised protocol. Suspected benign
      disease was verified by follow-up examination and clinical data, suspected
      malignant disease was correlated with biopsy or surgery. RESULTS: For the
      detection of tumor the overall concordance was 92%, the sensitivity 98% and the
      specificity 70% (6 false positive, 1 false negative). Resectability was correctly
      assessed in 90% with a sensitivity of 92% and a specificity of 88% (4 false
      positive, 4 false negative). Vascular invasion was detected correctly in 91%
      (veins)-94% (arteries), lymph node invasion in 67% and liver metastasis in 94%.
      CONCLUSION: Dual phase helical CT is a very reliable tool in the assessment of
      resectability in pancreatic cancer.

PMID- 9551106
TI  - [In vitro investigations for detection of vascular stenosis using spiral CT
      angiography].
AB  - PURPOSE: This experimental study investigates the suitability of spiral CT
      angiography for detection of stenoses. MATERIAL AND METHODS: Three vessel
      phantoms of 4, 7, and 10 mm diameter were scanned with spiral CT several times
      using different scanning parameters each time. Axial scans were viewed in
      different ways. Stenoses were adjusted axial, oblique, and parallel to the scan
      plane, and in between. 7 radiologists had to make a total of 630 decisions about
      the detectability of stenoses. RESULTS: Adequate scan and reconstructional
      parameters improve detection of stenoses significantly. 100% recognition can be
      reached with 5 mm layer thickness and table feed and 2 mm reconstructional
      interval provided axial scans are viewed in cine mode on a monitor. Vessels
      running parallel to the layer plane show better results than vessels axial to the
      plane, which in turn show better results than those running oblique. Vessels of 4
      to 10 mm diameter are almost equally suitable. CONCLUSIONS: Viewing axial scans,
      the detectability is rather influenced by different locations of stenoses than by
      varying vessel diameters.

PMID- 9551107
TI  - [Acute ischemic cerebral infarct: prospective serial observations by magnetic
      resonance imaging].
AB  - AIM: Serial observations of acute ischaemic cerebral infarcts by MRI in order to
      define signal patterns, contrast uptake, oedema and secondary haemorrhage over a
      period of three months. METHODS: Prospective serial examinations of 34 patients
      with acute cerebral ischaemia who were examined during the first 48 hours, on
      days 3 or 4, 7, 14, 21, 28 and after three months by MRI (spin echo TR/TE
      2200/100/20, 500/20, +/- Gd). RESULTS: T2 weighted spin echo sequences showed the
      highest sensitivity (88%) during the first 8 hours of cerebral ischaemia when
      compared with other spin echo sequences. Parenchymal contrast enhancement showed
      a distinct peak during the second and third weeks. The use of contrast did not
      improve diagnosis of an infarct during any stage. 87% of lesions showed
      haemorrhage at some stage. Vascular enhancement was observed in 25% of infarcts
      during the first 24 hours and was still present after three months in 20%.
      Parenchymal and vascular enhancement, and haemorrhage correlate with the size of
      the infarct. CONCLUSION: Focal cerebral ischaemia produces an abnormality of the
      blood-brain barrier, oedema and finally necrosis, depending on the severity and
      duration of the lesion. Haemorrhage in 87% was considerably more common than has
      been described previously. Vascular enhancement is not an early sign of an
      infarct, contrary to what has been described in the literature.

PMID- 9551108
TI  - [T1-weighted dynamic MRI with new superparamagnetic iron oxide particles
      (Resovist): results of a phantom study as well as 25 patients].
AB  - PURPOSE: Evaluation of the diagnostic usefulness of the T1-effect of Resovist
      (SPIO) for dynamic MRI of the liver. METHOD: In-vitro measurements of a dilution
      series with T1-weighted FLASH and SE sequences and investigation of 25 patients
      with known focal liver lesions with a T2-weighted TSE sequence and a dynamic T1
      FLASH sequence. RESULTS: T1-weighted MRI with Resovist in vitro showed a positive
      enhancement at low concentrations and a negative enhancement at higher
      concentrations. In-vivo T1-weighted dynamic MRI liver parenchyma demonstrated a
      positive enhancement 30 s post contrast, followed by a continuous slope of signal
      intensity and a negative enhancement (> or = 60 s). Spleen, portal venous vessels
      and haemangiomas showed an early increase in signal intensity followed by a
      decreasing positive enhancement, but without negative enhancement. During the
      perfusion phase metastases showed a small but not significant increase in signal
      intensity. In 80% a positive ring enhancement could be observed around
      metastases. CONCLUSION: Resovist exhibits a diagnostically useful T1-effect. An
      evaluation of the perfusion of focal liver lesions during the distribution phase
      is possible with dynamic T1-weighted MRI. This approach may further improve
      characterisation of focal liver lesions.

PMID- 9551109
TI  - [When is it meaningful to support magnetic resonance tomography by administering
      a positive enteral contrast medium?--an account of practical experience].
AB  - PURPOSE: To evaluate in which parts of the gastrointestinal tract and in what
      clinical situations the diagnostic quality of MR examination may be improved by a
      positive enteral contrast agent. METHODS: MR examinations of 37 patients
      performed before and after application of a Gadolinium-DTPA preparation suitable
      for oral and rectal application were evaluated. Exams were evaluated by two
      independent observers. Neoplastic disease of the gastrointestinal tract
      constituted the majority of indications followed by inflammatory changes and
      extraenteral space-occupying lesions. RESULTS: The majority of examinations (62%)
      were improved by the application of enteral contrast agent. No effect was
      observed in 35%; in two patients image quality was poorer after contrast
      application. The benefit of enteral contrast agents was highest in MR
      examinations of the sigma and rectum. The enteral contrast agent was most
      valuable in the detection of lymphoma if an evaluation according to indication
      was performed. CONCLUSION: In selected cases, the diagnostic quality of abdominal
      MRI can be improved by the application of an enteral contrast agent. Apart from
      the effect of greater signal intensity, the contrast agent does complement MR
      imaging by a functional aspect.

PMID- 9551110
TI  - [Combined use of ECK-triggered 2D-phase contrast MR angiography and 2D-time-of
      flight MR angiography for planning and follow up before and after vascular
      intervention of pelvic and leg arteries].
AB  - PURPOSE: To develop a strategy for the complete work-up of vessel lumen and
      vessel wall for planning and follow-up of radiological interventions of lower
      extremity arteries. METHODS: A total of 36 patients (21 pre-, 8 post- and 7 pre-
      and postinterventional) were studied. MRA studies were performed using an ECG
      triggered phase contrast technique for the demonstration of intraluminal flow and
      an axial high resolution time-of-flight technique to assess the vascular wall.
      All MRA studies were analysed by intraindividual DSA comparison for the
      assessment of flow and wall structures. RESULTS: Combined MRA techniques provided
      a good correlation with DSA for the assessment of vascular flow. The kappa test
      revealed a value of greater than 0.61 for most on the vessel segments proving a
      good correlation of both methods. Orthogonal high-resolution TOF-MRA provided
      additional information for the assessment postinterventional wall haematomas and
      hard plaques. CONCLUSION: Combination of PCA to study flow and axial TOF to study
      wall pathology improves the usefulness of peripheral MRA.

PMID- 9551111
TI  - [31P-mr spectroscopy of peripheral skeletal musculature under load: demonstration
      of normal energy metabolites compared with metabolic muscle diseases].
AB  - PURPOSE: 31P-MR spectroscopy of skeletal muscle under exercise was used to obtain
      the range of normal variation and comparison was made for different neuromuscular
      diseases. METHODS: 41 examinations of 24 volunteers and 41 investigations in 35
      patients were performed on 1.5 T MR systems (Gyroscan 515 und S15/ACSII,
      Philips). Localised 31P-MR spectra of the calf muscle were obtained in time
      series with a resolution of 12 s. RESULTS: Two types of muscle energy metabolism
      were identified from the pattern of spectroscopic time course in volunteers:
      While the first group was characterised by a remarkable decline to lower pH
      values during exercise, the second group showed only small pH shifts (minimum pH:
      6.48 +/- 0.13 vs 6.87 +/- 0.07, p < 10(-6)) although comparable workload
      conditions were maintained. The pH-values correlated well with blood lactate
      analysis. Patients with metabolic disorders and chronic fatigue syndrome (CFS)
      showed decreased resting values of PCr/(PCr + Pi) and increased pH levels during
      exercise. PCr recovery was significantly delayed (0.31 vs 0.65 min-1, p <
      0.00005) in metabolic muscle disorders but was normal in CFS patients.
      CONCLUSION: Findings in volunteers indicate utilisation of different metabolic
      pathways which seems to be related to the fibre type composition of muscle.
      Reduced resting levels for PCr/(PCr + Pi), altered pH time courses, and decreased
      PCr recovery seem to be helpful indicators for diagnosis of metabolic muscle
      disorders.

PMID- 9551112
TI  - [Duplex sonography of renal artery stenosis: potentials and limits of frequency
      spectrum analysis of arterial segments compared with angiography].
AB  - PURPOSE: The aim of this prospective study was to evaluate the potentials and
      limits of Doppler waveform analysis of intrarenal vessels in patients with
      suspected renal artery stenosis. MATERIAL AND METHODS: In a three-year study we
      compared our colour Doppler results of 111 patients with the angiography results.
      Evaluated parameters were acceleration time (AT), acceleration index (AI) and
      early systolic peak (ESP). RESULTS: The sensitivity of severe stenoses (> or =
      70%) was 89%. In moderate stenoses (50-70%) it was possible to increase the
      sensitivity from 56% to 76% if a comparison with the contralateral side was
      included. The specificity was 91%. Causes for limited sensitivity and specificity
      were poor examination conditions, stenoses of accessory renal arteries and
      moderate stenoses as well as diffuse non-stenosing lesions. CONCLUSION: In
      comparison with angiography, the diagnostic value of Doppler waveform analysis in
      the detection of renal artery stenoses has specific limitations. In significant
      stenoses, however, additional valuable haemodynamic information, useful for PTA,
      can be obtained by this easy and accessible method.

PMID- 9551113
TI  - [Comparative findings of digital thoracic images and digital images of
      statistical phantoms as film copy, a radiological work station and a PC].
AB  - INTRODUCTION: An ROC analysis was carried out in order to determine the
      reliability of digital luminescence radiography review at a PC and this was
      compared with a radiological work station and with X-ray film on a viewing box.
      MATERIAL AND METHOD: 54 chest images obtained by digital luminescence radiography
      were selected, 31 of these contained small pulmonary nodules. In order to
      evaluate critical detail, five images of a phantom showing round foci were used.
      Five radiologists examined these, using a Siemens Magic View work station, a PC
      with proprietary software (ViewMed) and X-ray films on a viewing box. Image
      processing of the work station used the standard clinical application. ViewMed
      performs linear scaling of grey levels to 8 Bit. The results were examined
      statistically by means of a t-test. RESULTS: As far as the chest images were
      concerned there was no significant difference in the diagnostic value of these
      methods. There was, however, a highly significant loss of diagnostic information
      with respect to the round focus phantom when using the PC compared with the other
      methods. CONCLUSION: In the configuration in which it was used, the PC should not
      be relied on as a primary means of examination since critical details cannot
      always be seen. In routine use these play a subordinate role and there was no
      significant diagnostic loss where the chest images were concerned. We expect that
      by improvements in the frequency and contrast processing the PC accuracy will be
      considerably increased.

PMID- 9551114
TI  - [Radiation exposure of radiation-sensitive risk organs--ocular lens, parotid
      gland, thyroid gland--in dacryocystography and therapy].
AB  - PURPOSE: Evaluation of radiation dose to the radiosensitive head and neck organs
      and tissues-ocular lens, parotid and thyroid glands--during dacryocystography and
      fluoroscopy--guided dacryocystoplasty (DCP). METHOD: Radiation dose was
      determined in an Alderson Rando phantom and in 13 patients. Radiation dose was
      measured directly using Ca-F2-thermoluminescent dosimetry crystals (TLD) which
      were placed on each eyelid, parotid gland and thyroid gland. RESULTS: The mean
      radiation dose to the lens placed next to the path of radiation was 6.58 mGy in
      the Alderson-Rando phantom and 5.43 mGy in patients during DCP. The mean
      radiation dose to the contralateral lens was 1.37 mGy and 1.7 mGy to the parotid
      gland placed next to the x-ray tube. Radiation dose to the thyroid gland was max.
      0.4 mGy during DCP. CONCLUSION: Radiation dose to the ocular lens, parotid gland
      and thyroid gland during fluoroscopy-guided DCP was 25 times higher than during
      diagnostic dacryocystography. The radiation dose to radiosensitive head and neck
      organs and tissues during fluoroscopy-guided DCP is much below the threshold dose
      for ocular lens cataract.

PMID- 9551115
TI  - [Treatment of arterial aneurysms of the pelvic leg vessels using dacron covered
      nitinol stents].
AB  - PURPOSE: To evaluate the success rates of the implantation of stent grafts in the
      treatment of peripheral aneurysms. MATERIALS AND METHODS: In 13 patients with 15
      aneurysms at the common iliac artery (n = 6), external iliac artery (n = 1),
      hypogastric artery (n = 2), femoral artery (n = 2) or popliteal artery (n = 4),
      implantation of dacron-covered nitinol stents was performed. The patients were
      followed up for three to 20 months (mean, 8.8 months) with intravenous digital
      subtraction angiography, CT or colour-coded Doppler sonography. RESULTS: In all
      cases, the aneurysm was successfully occluded after stent implantation. In one
      case with a popliteal aneurysm, kinking of the vessel caused thrombosis of the
      stent. The stent was successfully reopened. The aneurysm however, had to be
      surgically treated 9 months later. The primary and secondary patency rates at 6
      months were 93% and 100%, respectively. CONCLUSION: The method described might be
      an alternative therapy to surgery. There are some limitations in respect of
      treatment of popliteal aneurysms.

PMID- 9551116
TI  - [CT guided percutaneous drainage of retro- and extraperitoneal abscesses and
      fluid collection].
AB  - PURPOSE: Evaluation of course, success rate and complications after CT-guided
      percutaneous drainage of retroperitoneal and extraperitoneal abscesses and fluid
      collections (PAFD). METHODS: Retrospective review of 47 PAFD in 42 consecutive
      patients (27 male, 15 female, age 58 [27-80] years) over a period of 7 years was
      performed. RESULTS: 47 clinically suspected abscesses proved to be 40 abscesses,
      three haematomas and 4 lymphoceles. Primarily, 67 drainage catheters were needed,
      which included three catheters in 4 patients and 4 catheters in one patient.
      Drainage time averaged 17.6 days (2-50). The most frequent drainage location was
      the iliopsoas region (27/47 collections). The cure rate was 87.2% (41/47
      collections). Temporization was achieved in 8.5% (4/47); there were two drainage
      failures (one sepsis, one recurrence). No major complications were observed.
      Three catheter dislocations occurred as minor complications. CONCLUSION: CT
      guided percutaneous drainage of retroperitoneal and extraperitoneal abscesses and
      fluid collections is safe, with a high cure rate and few complications.

PMID- 9551117
TI  - [Stereo display of MR angiograms].
AB  - PURPOSE: To provide methods for stereoscopic visual demonstration from 3D
      reconstructed MR angiographic images. METHODS: Stereoscopic viewing can be
      obtained with pairs of images that are displayed at angles of 15 degrees. Optical
      devices as stereoscopic binoculars or minor stereoscopes facilitate stereoscopic
      viewing. The possibility of stereoscopic projections for a larger auditorium is
      mentioned. RESULTS: Using three clinical examples the advantages of stereoscopic
      display of MR angiograms are demonstrated. CONCLUSIONS: MR angiography allows
      stereoscopic viewing with simple methods, like CT- and conventional rotation
      angiography. This principle, which has been known for 100 years, may thus acquire
      a new significance.

PMID- 9551118
TI  - [Compression therapy of a ruptured spurious aneurysm].

PMID- 9551119
TI  - [Lipomatous hypertrophy of the interatrial septum: imaging by echocardiography,
      CT and MRT].

PMID- 9551120
TI  - [CT monitored transcervical puncture of an epidural abscess at the level of the
      atlantodental joint].

PMID- 9551121
TI  - [Pulmonary manifestation of juvenile laryngotracheal papillomatosis].

PMID- 9551122
TI  - [Metastasis of a papillary cystadenocarcinoma of the ovary in an axillary lymph
      node].

PMID- 9551123
TI  - [Disputed concept in polytrauma: whole-body spiral CT as primary diagnosis (RoFo
      166,5 (1997) 382-8)].

PMID- 9551124
TI  - Modeling in manual materials handling.
AB  - Manual materials handling (MMH) account for approximately $15.0 billion of
      injuries cost in the United States alone. Because of the need to establish manual
      handling guidelines, different approaches to achieve this goal were pursued. Such
      approaches are based on biomechanics, work physiology, and psychophysics. In
      order to better understand the MMH system's behavior, models were developed.
      These models can be divided into biomechanical models, physiological models,
      psychophysically based capacity models, safe load handling models, and simulation
      models. This paper will present a sample of these models and discusses their
      advantages and disadvantages.

PMID- 9551125
TI  - Work-related musculoskeletal problems: Some ergonomic considerations.
AB  - Musculoskeletal disorders (MSD) in industrialized and industrializing countries
      are situated and discussed. Considerations are made on the registration of MSD
      cases, on the consequences for humans, industry and society, on scientific
      methodology and prevention strategies. These considerations are used to develop
      proposals for future actions. These concern the development of structures, some
      ideas about training and education as well as a common method for applied field
      research enabling the use of data in all industries.

PMID- 9551127
TI  - An improved method for describing the effects of heat radiation on men.
AB  - At industrial workplaces radiant heat load is often the dominant heat stress
      factor. Based on 900 climatic chamber experiments on humans, this study was
      conducted to develop a physiologically validated index-method to evaluate
      climates with intensified heat radiation. A comparison shows that the
      international recommended heat stress indices are not suitable to evaluate such
      climates correctly. By application of the new index-method into the commonly used
      indices, the improvement for the prediction of thermal stress effects in view of
      climates with increased heat radiation is discussed.

PMID- 9551126
TI  - Factors affecting heat illness when working in conditions of thermal stress.
AB  - In hot working conditions, high sweat rates with excessive loss of body fluids
      may result in dehydration and electrolyte imbalance. It is well established that
      dehydration and/or electrolyte disturbances will impair work performance, and, if
      prolonged or severe, can pose a serious risk to health. The lesser condition of
      hypohydration is undoubtedly widespread in the workplace, and may be indirectly
      responsible for less than optimal performance and workplace accidents. With the
      aid of a new sweat collection method, fluid and electrolyte loss from a
      population of male workers with varying fitness and body composition has been
      documented. This has provided the basis for prescribing guidelines of fluid
      replacement when working in the heat. In addition, the minimum duration of heat
      exposure required to trigger heat acclimmatization was sought using sweat sodium
      as an indicator. Rehydration at the rate of 500 ml/h (250 ml every 30 min) is
      recommended for people working in all but extreme heat (> 45 degrees C).
      Electrolyte supplements (sodium and potassium) are not generally required in the
      workplace, but may be warranted in certain circumstances to avoid hyponatremia (>
      3 h). The ability to predict the susceptibility of an individual to fluid and
      electrolyte disturbances cannot be made from age, body composition, ethnicity or
      VO2max, although a high VO2max appears to enhance heat tolerance. Sodium loss in
      sweat varies greatly and is not significantly related to sweat rate.
      Acclimatization results in a significant decrease in sweat sodium and increased
      sweat rate during summer compared with winter. This advantageous physiological
      adaptation requires a minimum of 9 h of heat exposure to initiate.

PMID- 9551128
TI  - Balinese dance exercises improve the maximum aerobic capacity.
AB  - The maximum aerobic capacity can be used to predict the maximum working capacity.
      The maximum working capacity plays an important role in achieving the best
      performance. Therefore, physical fitness program for maintaining maximum working
      capacity is a must. A study on the application of Balinese dance exercise was
      carried out. Sixty young male Balinese, aged from 17 to 19 years were used as
      subjects. They were divided into two groups: Experimental group (EG) and control
      group (CG) based on their VO2max. The EG participated in a program of Balinese
      dance exercise 3 x 50 min per week for 8 weeks. Pretest-posttest control group
      design was applied. The maximum aerobic capacity was measured, based on the
      Modified Harvard Step-up Test and nomogram of Astrand. The results are as
      follows: there is a very significant improvement of VO2max from 2.7 +/- 0.5 l/min
      or 51.1 +/- 9.1 ml/kg/min into 3.1 +/- 0.5 l/min or 58.9 +/- 9.8 ml/kg/min. Other
      parameters such as resting heart rate, blood pressure and percent body fat were
      decreased significantly. The study concludes that Balinese dance exercise could
      be used as a program for physical fitness maintenance.

PMID- 9551129
TI  - Use of physiological criteria for improving physical work conditions.
AB  - Physical work is still present in many countries, specially in developing ones.
      The physiological analysis of the work load could be conducted through two
      different ways, referring to his energetic cost and/or to the mechanical power of
      the human motor. The purpose of ergonomics is to organize any physical
      professional task in order to maintain the workers as much as possible inside the
      limits of a fatiguing activity. The process of fatigue affects differently a
      "general activity" and a "local work." If a worker is engaged in a general hard
      activity, like carrying a load or pushing a trolley, an increase of oxygen
      consumption or/and an acceleration of the heart rate could be observed. This
      latter, allowing to estimate the oxygen cost of the work, is more affected if the
      work is performed in a hot environment. In order to establish the ratio between
      the data observed at the work place and the maximal working capacity of the
      organism, it is possible to experiment with the physiological effects of
      transitory increases of the work stress, by increasing the load or/and the
      frequency of the repetition of the "unit" of work done. When the task could be
      described in terms of local work, the correct methodology is based upon the
      general rules established respectively for the static and the dynamic work. In
      both the cases, it is possible to determine the critical rate of the muscular
      activity, the part of the muscular capacity engaged at the work place and the
      probable time for local exhaustion, in order to limit the duration of each period
      of work. It should be remembered that 50 years ago, Lucien Brouha proposed that
      heart rate determinations at work be used as a criteria for a better organization
      of human work by a non-sophisticated method.

PMID- 9551130
TI  - Development of an anthropometric database for Hong Kong Chinese CAD operators.
AB  - With the increasing popularity of using computer-aided design (CAD) in Hong Kong,
      it is time to look into the design of a suitable workplace for the CAD operators
      working in the industries. This can be achieved by applying anthropometric data
      into the design for enhancing performance and reducing musculoskeletal problems.
      In order to avoid any mismatches in anthropometric dimensions, which is believed
      to be one of the main causes of fatigue and occupational illness among workers,
      in the workplace design for them, eleven relevant body dimensions from a group of
      150 Hong Kong male adults with ages ranging from 18 to 28 years were collected
      and analyzed to develop a computerized anthropometric database for Hong Kong CAD
      operators. The eleven anthropometric dimensions measured were: shoulder rest
      height, elbow-fingertip length, shoulder breadth, hip breadth, sitting eye
      height, elbow rest height, third lumbar disc-pan length, thigh clearance height,
      popliteal height, buttock-popliteal length, and stature. The computerized
      database can provide some useful statistics such as mean, standard deviation and
      relevant percentiles of all the measured dimensions. With the aid of these
      statistics, a new workplace for CAD operators was designed which improved
      performance substantially.

PMID- 9551131
TI  - Improvement of Tsukiji free fish market in Tokyo ("Kaizen" of work environment).
AB  - "TSUKIJI" is one of the biggest and most famous Free Fish Markets in the world,
      but there are many problems on the working condition because it was built about
      60 years ago. Our investigation was held 1991 to 1993 to give some improvements
      regarding layout of buildings, working time, heat condition at refrigerator,
      working posture, and so on. We used a questionnaire on daily life and health care
      of workers, time study with measurement of heartbeats, and checklist (using
      Checklist for Improvement of Safety-Health and Working Conditions,' made by ILO).
      The main occupations in TSUKIJI were seller, buyer, delivery worker, and
      refrigerator maintenance worker. Their starting time was early in the morning,
      usually between 2:00 a.m. and 5:00 a.m., but the hardest one was delivery workers
      starting at 9:00 p.m. They used auto cargo car for carrying to shops from
      refrigerator or from auction places many times. Sellers had two different types
      of work. First, the seller set up the auction, numbering the fish (or cases of
      seafood), arranging them in order, and so on. The rest of the work was
      transaction of invoices, sometimes using VDU with almost sitting. These works did
      not look well balanced. Buyer of tuna cut if like lumber by electric saws did not
      have guard for protection and there were more than 200 machines. Overlooking the
      market by checklist, some problems were clarified, and suggestions for
      improvement include restructuring the whole layout of the market or reforming
      buildings, standardization of the cases, adjustment of health facilities, safety
      protection on tools and machines, management of working system, working posture,
      health care, and so on.

PMID- 9551132
TI  - Ergonomic task analysis in electronics industries: some case studies.
AB  - The analyses of a few tasks were carried out in an electronics factory. The main
      objectives are to identify the ergonomic and biomechanical hazards of problem
      work tasks, to analyze each task systematically in order to evaluate the workers'
      exposures to the risk factors of force, posture pressure and repetition and to
      make recommendations to reduce the risks and hazards. The methodology includes
      objective measures--detailed analysis by going through training manuals, job
      description and production records. Subjective measures include interviewing the
      operator and supervisors informally, the operators were also required to fill in
      a structured questionnaire. The paper concludes by making recommendations to
      reduce the ergonomic hazards by engineering solutions, redesign or administrative
      controls or the implementation of procedures.

PMID- 9551133
TI  - Improvement of working posture increases productivity of roof tile home industry
      workers at Darmasaba Village, Badung Regency.
AB  - In the production process of the roof tile home industry in Darmasaba Village,
      Badung Regency, bad working postures such as bending and squatting positions were
      observed. It caused an inefficient low speed of work as a consequence. Therefore,
      an intervention study in forms of a demo-plot was carried out, introducing the
      correct working posture and working method. The process of plating clay material
      is done on the desk in a standing position and can be performed continuously,
      without waiting for any other works. By so doing, it was found that productivity
      of workers increased 20% per day.

PMID- 9551134
TI  - Effects of working postures on low back pain.
AB  - The prevalence of back pain in a sample of 100 employees in a clothes factory was
      studied and predisposing factors especially working postures were analyzed. The
      employee's ages were 17-40 years (mean 28 years). Durations of employment were
      between 1 month to 21 years (mean 9.4 years). Working time per day was 8 h. The
      subjects included 18 males and 82 females. The prevalence of back pain was 38%.
      Working activities like lifting, pulling and pushing, bending and sitting were
      highly associated with low back pain. Standing and walking were also associated
      but with a lower prevalence.

PMID- 9551135
TI  - Applying task analysis in design specification: current problems and a solution.
AB  - This paper addresses the following criticisms of task analysis: its requirement
      for an existing system; its focus on analysis rather than design; its limited
      scope within the design cycle; its underspecification of the application domain;
      and its inadequate documentation of design outputs. Such criticisms constitute
      problems for the application of task analysis. Solutions to these problems have
      emerged indirectly from the development of a structured method intended to
      rectify the typically late involvement of human factors in system development,
      e.g. only at the evaluation stage. This paper describes how task analysis has
      been extended and incorporated throughout the design cycle.

PMID- 9551136
TI  - Ergonomics application in the N250 aircraft design process, approach, analysis,
      and assessment model.
AB  - In the decade of the 1990's the human aspect has once again taken center stage in
      the design and operation of commercial aircraft. As occupation health and safety
      has gained importance in society in general, it has gained even more importance
      in the design an operation of commercial aircraft. In aircraft design today, the
      man-machine interface is considered in every task of the human workload. The
      discipline of ergonomics truly impacts each phase of product or tool design. At
      IPTN, the ergonomics effort is principally being applied to the design of the
      cockpit, cabin and cargo compartment of the N250. The ergonomists at IPTN are
      keenly aware that there would be a conflict between the user and his working
      environment without proper attention to the human considerations in the design is
      left for ergonomists and innovative programs like IPTN's participatory approach,
      to ensure that the human aspect is optimized in the man-machine interface.

PMID- 9551137
TI  - A study of impact of shift work on fatigue level of workers in a sanitary-ware
      factory using a fuzzy set model.
AB  - Work generally affects workers in terms of both physical and mental health.
      Workers must adapt their life pattern to match shift-work styles which can result
      in family problems, increased fatigue level, lower work efficiency, higher
      accident rate, illnesses, and lower productivity. The project obtained an entry
      permission to study the impact of shift work on fatigue level of workers in a
      sanitary-ware factory. The objectives were: 1) to evaluate fatigue levels of
      workers who worked in the morning shift and night shift, and 2) to prioritize
      contributing factors affecting fatigue levels using a model of fuzzy set theory.
      Twelve male workers participated in the study. Four subjects were recruited from
      each of 3 departments, i.e., glazing, baking and quality inspection. The
      measurement was conducted before and after the shift for both shifts. Variables
      included heart rate monitoring throughout the work shift, critical flicker fusion
      frequency, reaction time response, hand-grip strength, and wet-bulb globe
      temperature. Results were analyzed using a computerized statistical package. It
      was concluded from this study that mental fatigue from working in the morning
      shift was significantly higher than the one for working in the night shift. The
      same indication was also true in the case of physical fatigue, though it was not
      statistically significant. From the fuzzy set analysis, it was confirmed that
      working in the morning shift resulted in a higher fatigue level than working in
      the night shift and the temperature of the work environment was the most
      important factor contributing to the higher fatigue level.

PMID- 9551138
TI  - Reliability of inferred age, and coincidence between inferred age and
      chronological age.
AB  - Outdoor research is restricted by many factors. The age inference was one of the
      biggest problems for the outdoor researchers. We have investigated the
      reliability of inferred age for the Japanese people, and took out the estimation
      formula for the age, even if it was based on the inferred age. The age
      classification was the most popular method for this purpose, and there were many
      classifications. We took the classification of young, middle aged, and elderly
      groups, in which classification of the SDs were rather small, that is, 4, 5, and
      7 years for the young, middle aged, and elderly age groups, respectively.

PMID- 9551139
TI  - Therapeutics in atopic dermatitis.

PMID- 9551140
TI  - Neutrophilic tissue reactions.

PMID- 9551141
TI  - Update on cutaneous drug reactions.

PMID- 9551142
TI  - Generalized atrophic benign epidermolysis bullosa.
AB  - Junctional EB was once considered a uniformly fetal autosomal recessive skin
      disease. One of the first and best characterized forms of generalized JEB that
      has a more favorable prognosis was GABEB. Since its initial description in 1976,
      many additional cases have been compiled, all sharing the features of chronic
      blistering from birth, nail dystrophy, hair loss, and abnormal teeth. In
      addition, some patients have large melanocytic nevi that form at sites of prior
      blisters. The first clues as to the protein defective in these patients was
      provided by immunofluorescence microscopy studies, which showed absent or
      decreased expression of type XVII collagen in these patient's epidermal BM. This
      protein was a promising candidate because it is located in the ultrastructural
      plane where blisters from in patients with GABEB. It is also the same
      hemidesmosomal protein against which antibodies are directed in patients with
      autoimmune blistering diseases: bullous, gestational, and cicatricial pemphigoid.
      The demonstration of decreased expression of type XVII collagen in patients with
      GABEB pointed the way to a crucial distinction that could not be based on
      clinical and histologic findings--that of discriminating infants with GABEB from
      those with the lethal Herlitz variant of JEB. These two diseases may be
      differentiated because decreased expression of type XVII collagen is found
      exclusively in GABEB, whereas decreased expression of laminin 5 is most likely
      associated with Herlitz JEB. The molecular basis of GABEB has been determined.
      The immunofluorescence microscopy studies mentioned above directed mutation
      studies to the COL17A1 gene. Several mutations in COL17A1 have been described in
      patients with GABEB, almost all of which result in a PTC. As a consequence of the
      PTC, mutant COL17A1 transcripts are rapidly degraded by nonsense-mediated mRNA
      decay, blocking production of type XVII collagen from the mutant allele.
      Heterozygous carriers of the mutation are thus rendered untouched by the
      mutation. In the homozygous state, however, this results in the absence of this
      vital adhesion protein, leading to chronic blistering and skin fragility observed
      in these patients. These studies also significantly increase our knowledge about
      the normal functions of type XVII collagen. The fact that patients deficient in
      type XVII collagen have fragile skin attests to the role of this protein in the
      adhesion of basal keratinocytes to epidermal BM. The severity of GABEB, however,
      is much less than that observed in patients with a complete deficiency of laminin
      5, suggesting that type XVII collagen functions cooperatively with other
      hemidesmosomal proteins in promoting adhesion. Studies using GABEB keratinocytes
      will help characterize these kinds of interactions. The ultimate prospect of
      mutation analysis in these patients is the hope of correcting their genetic
      defect and curing their disease. Until then, the physician plays an important
      role in making the diagnosis, providing general supportive skin care, advising
      avoidance of trauma, treating infections, and supporting the patient's
      psychosocial development. Further studies of patients with GABEB will lead to new
      therapeutic approaches, as well as reveal additional complex functions of type
      XVII collagen not only in skin, but also in hair, teeth, and nails.

PMID- 9551143
TI  - The regulation and function of the p53 tumor suppressor.

PMID- 9551144
TI  - Molecular genetics of skin cancer.

PMID- 9551145
TI  - The role of immunohistochemistry in the diagnosis of cutaneous lymphoma.

PMID- 9551146
TI  - Interferons in dermatology: biology, pharmacology, and clinical applications.

PMID- 9551148
TI  - Photosensitivity disorders in childhood.

PMID- 9551147
TI  - Minimal deviation melanoma: concept or quagmire?

PMID- 9551149
TI  - Nail diseases in children.

PMID- 9551150
TI  - Vascular tumors and vascular malformations (new issues).

PMID- 9551151
TI  - Pitfalls in frozen section interpretation in Mohs micrographic surgery.

PMID- 9551152
TI  - Laser resurfacing.

PMID- 9551153
TI  - Treatment of benign vascular lesions with the Photoderm VL high-intensity pulsed
      light source.

PMID- 9551154
TI  - [Anatomo-clinical prognostic factors of papillary carcinoma of the thyroid.
      Multivariate analysis: report of a series of 52 cases].
AB  - A retrospective study about 52 cases of papillary thyroid carcinomas was carried
      out with emphasis on histopathological features. The mean follow up period was 10
      years. The survival curves were estimated using the Kaplan-Meier method and
      compared using the log rank test. The multivariate analysis was performed using
      the Cox's regression model. In univariate analysis, age, Tp (histopathological
      extension of the tumor), histological differentiation, VAN score (Vascular
      invasion nuclear Atypia tumor Necrosis) of Akslen and the LeuM1 expression were
      significant prognostic factors. In multivariate analysis, the Tp and histological
      differentiation were associated with high risks of poor outcome.

PMID- 9551155
TI  - [Epstein-Barr virus: pathologic implications].

PMID- 9551156
TI  - [Classification of primary kidney tumors in adults].

PMID- 9551157
TI  - [Primary angiosarcoma of the central nervous system: report of a case].

PMID- 9551158
TI  - [Lipoma of the internal auditory canal. Report of two cases simulating acoustic
      neuroma].
AB  - We report two cases of intra-auditory canal lipoma, presenting as acoustic
      neuroma, observed in respectively 45 and 53 year old patients. Cerebellopontine
      angle lipomas are unusual lesions, more exceptional than their intracranial
      counter-parts. The knowledge of these tumoral lesions and of their close
      relationships with cranial nerves incite to perform a frozen section when imagery
      is evocative, to limit functional postoperative sequelae.

PMID- 9551159
TI  - [Stomatococcus mucilaginosus infection. A rare cause of cutaneous histiocytic
      infiltrate].
AB  - We report the case of a systemic infection due to Stomatococcus mucilaginosus
      with cutaneous localisations occurring in a neutropenic child. The histological
      features of this cutaneous involvement are very unusual and the diagnosis can be
      suggested before bacteriological results.

PMID- 9551160
TI  - [Polycystic disease of the salivary glands: report of an attack of the
      submaxillary glands].
AB  - Bilateral dysgenetic polycystic disease of parotid glands is an extremely rare
      pathologic condition in which salivary parenchyma is partially replaced by
      multiple epithelial-lined cysts arising from intercalated ducts. Review of the
      fourteen cases published in literature shows that it affects nearly exclusively
      women with an history of asymptomatic progressive enlargement of almost always
      both parotid glands. We report here the first case, to our knowledge, of a
      polycystic disease involving both submandibular salivary gland in a man.

PMID- 9551161
TI  - [A pulmonary mass with a raging fever].

PMID- 9551162
TI  - [Nodule of the back of the foot with localized hyperhidrosis].

PMID- 9551163
TI  - [A granulomatous hepatitis].

PMID- 9551164
TI  - [Testicular metastasis revealing a gastric adenocarcinoma].

PMID- 9551165
TI  - [Practice of microscopic diagnosis of Helicobacter pylori infection on gastric
      biopsy in the laboratories of French Pathology. Hepatic and Digestive
      Histopathology Club].
AB  - The histological study of gastric biopsies is very much used for the diagnosis of
      Helicobacter pylori infection. A survey was performed among the members of the
      "Club d'Histopathologie Digestive et Hepatique" on the conditions of this
      diagnosis. The diagnosis is performed systematically by 91% of the pathologists.
      A special stain is used in 72% of cases (most often Giemsa), and
      immunohistochemistry is very rarely used. The classifications of gastritis that
      are frequently used are the Sydney system and the Whitehead's classification. In
      conclusion, it appears that the methods in use in France for the histological
      diagnosis of Helicobacter pylori infection are relatively homogeneous.

PMID- 9551166
TI  - [Serine/threonine type protein kinase activity in cell-free extracts of
      Streptomyces lividans].
AB  - Cell-free extracts of Streptomyces lividans prepared at the physiological ionic
      strength from the early logarithmic phase culture showed an endogenous protein
      kinase activity. Incubation of the salt soluble fraction of S.lividans with
      [gamma-32P]ATP led to incorporation of the labelled phospate into 6 to 7
      polypeptide chains of 12-100 kDa. Addition of heparine, polylysine, spermine,
      phosphatidylserine, kanamycin, cAMP and cGMP did not change the spectrum or level
      of the polypeptide phosphorylation in the extract while Ca2+ ions stimulated the
      protein phosphorylation. It was shown that the protein kinase(s) catalyzed
      binding of the phosphate groups to the serine and thereonine residues in the
      polypeptides with M(r) 100 and 35 kDa.

PMID- 9551167
TI  - [Development of a solid-phase immunoenzyme analysis of gentamicin in human blood
      serum].
AB  - An enzyme immune test system was designed and optimized for quantitative assay of
      gentamicin in human sera. Immunospecific reagents i.e. gentamicin conjugates with
      ovalbumin (for sorption on polysterol plates) and with bovine serum albumin
      (immunogen) were prepared. Gentamicin specific antisera were isolated and tested.
      Conditions for the antigen sorption on polysterol plates were determined and
      optimized. Different regimes of the competition reaction were investigated and
      conditions for the antibiotic assay in human sera were determined. The assay
      specificity was studied and the stability of the test system was checked. An
      experimental lot of the reagent set was manufactured at the ZAO NPP Immunotech
      and the correlation tests with the use of the fluorescence polarization
      immunoassay were performed. The set is destined for the assay of 40 samples (in
      duplicate). The method sensitivity is 1 ng/ml of gentamicin. The range of the
      detectable concentration is 1 to 32 ng/ml of gentamicin in 1000-fold diluted
      sera. The assay time is not more than 3 hours. The variation coefficient of the
      results does not exceed 12 per cent. The shelf-life of the set is 0.5 years when
      stored at a temperature of 2 to 8 degrees C.

PMID- 9551168
TI  - [A new mathematical approach for determining antibiotic concentrations using the
      agar diffusion method].
AB  - A mathematical approach using the one-point intercept form of the equation of a
      straight line for the assay of antibiotic biological activity by the agar
      diffusion method is described. Insignificant alteration in the experimental
      conditions made it possible to markedly lower the volume of work and materials
      for the statistic processing. As distinct from the routine methods, the assay
      substance in three different concentrations is applied to three cavities on a
      dish and the standard substance in one control concentration is applied to the
      other three cavities on the same dish. The antibiotic biological activity is
      estimated from the equation lg cn = lg cst + (dn - dst)/bi when the relationship
      between the dose logarithm and the size of the diameters of the test microbe
      inhibition growth zones is direct. When the relationship is inverse e.g. when the
      dose is expressed as the dilution, the equation lg cn = lg cst + (dst - dn)/bi is
      used. Factor bi is determined experimentally for every sample by the mean value
      of the sizes of the inhibition growth zone diameter by the programs of the simple
      linear-regression.

PMID- 9551169
TI  - [Effect of probiotics from bacilli on macrophage functional activity].
AB  - The influence of new probiotics from bacilli i.e. biosporin and subalin on the
      functional activity of murine peritoneal macrophages was studied. After a single
      oral administration of the probiotics the maximum activation of the macrophages
      was observed in 4 hours. The activation level depended on both the dose and the
      probiotic. The highest value of the stimulation index was recorded with subalin.
      Analogous regularities were stated with parenteral administration of the
      probiotics. Some mechanisms of activation of peritoneal macrophages after oral
      administration of probiotics from live microbial cultures are discussed.

PMID- 9551170
TI  - [Antimicrobial properties of nitrogen oxide and regulation of its biosynthesis in
      macroorganism].

PMID- 9551172
TI  - [Lomefloxacin hydrochloride (Maxaquin), a long-acting fluoroquinolone
      (information for specialists)].

PMID- 9551171
TI  - [The difluoroquinolone lomefloxacin--an broad spectrum antimicrobial drug].

PMID- 9551173
TI  - The zebrafish's swim to fame as an experimental model in biology.
AB  - The zebrafish has long been the favorite organism in many scientific disciplines.
      Although its attributes as a model were expounded for many years and thus were no
      secret, the zebrafish sat in the wings while other more popular vertebrates such
      as chick, amphibians, and mouse were examined at length. We cannot say there was
      a resurgence in popularity, but more an explosion of research utilizing the
      zebrafish beginning in the late 1970s when investigators at the University of
      Oregon began using it as their model in neuroscience. Prior to this reawakening,
      the zebrafish was one of the significant organisms in the study of teratology and
      toxicology, development, and, to some extent, behavior. Recently, however, the
      field of zebrafish genetics has gained immense popularity and success, in part
      owing to the fact that zebrafish are diploid and are amenable to genetic
      manipulations. Here we present an overview of the multidisciplinary research that
      has laid some of the foundation of our present understanding of the biochemical,
      cell biological, and molecular genetic events accompanying zebrafish development.

PMID- 9551174
TI  - Heat shock genes and the heat shock response in zebrafish embryos.
AB  - Heat shock genes exhibit complex patterns of spatial and temporal regulation
      during embryonic development in a wide range of organisms. Our laboratory has
      initiated an analysis of heat shock protein gene expression in the zebrafish, a
      model system that is now utilized extensively for the examination of early
      embryonic development of vertebrates. We have cloned members of the zebrafish
      hsp47, hsp70, and hsp90 gene families and shown them to be closely related to
      their counterparts in higher vertebrates. Whole mount in situ hybridization and
      Northern blot analyses have revealed that these genes are regulated in distinct
      spatial, temporal, and stress-specific manners. Furthermore, the tissue-specific
      expression patterns of the hsp47 and hsp90 alpha genes correlate closely with the
      expression of genes encoding known chaperone targets of Hsp47 and Hsp90 in other
      systems. The data raise a number of interesting questions regarding the function
      and regulation of these heat shock genes in zebrafish embryos during normal
      development and following exposure to environmental stress.

PMID- 9551175
TI  - DNA methylation and genome imprinting in the zebrafish, Danio rerio: some
      evolutionary ramifications.
AB  - Although methylation has been recognized as an important component in a number of
      developmental processes in mammals, in zebrafish almost nothing is known about
      this epigenetic modification. This is despite the fact that the zebrafish is
      becoming increasingly popular as a developmental model system. The little work
      that has been done on methylation and development in fish concerns genomic
      imprinting. In mammals, imprinting results in an inability to reproduce
      parthenogenetically because a genetic contribution from both parents is necessary
      to successfully complete development. However, this is not true of zebrafish, and
      a number of the theories that have been presented to explain the evolution of
      imprinting are not consistent with imprinting in these fish. A new model is
      presented that discusses some of the potential evolutionary ramifications of
      methylation and imprinting and that leads to the suggestion that imprinting may
      actually be a simple genetic mechanism to enhance the efficient evolution of both
      individual genetic loci and combinations of loci with related functions, without
      risking the population as a whole. This model can accommodate all of the
      information known about imprinting, including its broad phylogenetic range,
      imprinting by both males and females, and the diverse nature of the genes that
      are known to be imprinted.

PMID- 9551176
TI  - Repetitive elements and their genetic applications in zebrafish.
AB  - Repetitive elements provide important clues about chromosome dynamics,
      evolutionary forces, and mechanisms for exchange of genetic information between
      organisms. Repetitive sequences, especially the mobile elements, have many
      potential applications in genetic research. DNA transposons and retroposons are
      routinely used for insertional mutagenesis, gene mapping, gene tagging, and gene
      transfer in several model systems. Once they are developed for the zebrafish,
      they will greatly facilitate the identification, mapping, and isolation of genes
      involved in development as well as the investigation of the evolutionary
      processes that have been shaping eukaryotic genomes. In this review repetitive
      elements are characterized in terms of their lengths and other physical
      properties, copy numbers, modes of amplification, and mobilities within a single
      genome and between genomes. Examples of how they can be used to screen genomes
      for species and individual strain differences are presented. This review does not
      cover repetitive gene families that encode well-studied products such as rRNAs,
      tRNAs, and the like.

PMID- 9551177
TI  - Genetic dissection of vertebrate processes in the zebrafish: a comparison of
      uniparental and two-generation screens.
AB  - Genetic dissection is used to identify important genes in biological processes
      and is accomplished through the generation and study of mutations in model
      organisms. In diploid organisms, recessive mutations must be rendered hemizygous
      or homozygous for the mutant phenotype to be detected. In zebrafish (Danio
      rerio), this can be accomplished in two ways: (i) crosses between siblings who
      are potential carriers (in two-generation screens) and (ii) the generation of
      uniparental progeny. Two-generation screens have been the most productive to date
      but require substantial resources. However, uniparental screens involving
      haploids and half-tetrads (products of meiosis I) have also been productive, and
      require more modest resources. In genetic screens, the fraction of an average
      genome that is heterozygous (heterozygosity index) is inversely proportional to
      the likelihood that separate recessive mutations will be homozygous at the same
      time. Heterozygosity indices for haploid, half-tetrad, and two-generation screens
      are 0, 66, and 87.5%, respectively. Family sizes required to minimize bias in
      half-tetrad screens are also calculated. We conclude that gynogenetic half-tetrad
      screens are genetically robust and technically accessible to the independent
      researcher. The increasingly powerful genetic and experimental tools available
      for work with zebrafish can be used to address a broad range of questions in
      vertebrate biology.

PMID- 9551178
TI  - High-resolution imaging at the cellular and subcellular levels in flattened whole
      mounts of early zebrafish embryos.
AB  - We describe a rapid and sensitive method for high-resolution imaging at the
      cellular and subcellular levels in the whole-mount zebrafish embryo. The
      procedure involves fixing and staining the embryo, followed by deyolking and
      flattening it under a cover slip, to produce a planar mount that is 20 to 100
      microns thick. Such a flattened whole mount allows imaging with a spatial
      resolution of approximately 500 nm in the x-y plane and does not require the use
      of embedding, sectioning, confocal microscopy, or computational deblurring
      procedures. We can resolve all individual nuclei and chromosome sets in the
      embryo, up to the late gastrula stage (10,000 cell stage). In addition, older
      embryos (through the segmentation stage) can also be examined, with the
      preservation of significant morphological detail. Because of its ability to
      resolve subcellular detail, the flattened whole-mount method can provide
      significant biological information beyond what can be obtained from conventional
      (three-dimensional) whole mounts. We have used the flattened whole-mount method
      to study subcellular events related to progression through the cell cycle or to
      apoptosis, in cells of the early zebrafish embryo. A specific DNA-binding dye
      (Hoechst 33258) or an antibody against a chromosomal protein (histone H1) was
      used to stain the nuclei of individual cells in the embryo. This allowed us to
      determine the spatial positions of all the individual cells, and also their
      stages in the cell cycle. A terminal transferase (TUNEL) assay was used to detect
      apoptotic cells. This combination of specific stains allowed us to study the
      behaviors of groups of cells in situ, within the developing zebrafish embryo.

PMID- 9551179
TI  - Regional cell movement and tissue patterning in the zebrafish embryo revealed by
      fate mapping with caged fluorescein.
AB  - Determination of fate maps and cell lineage tracing have previously been carried
      out in the zebrafish embryo by following the progeny of individual cells injected
      with fluorescent dyes. We review the information obtained from these experiments
      and then present an approach to fate mapping and cell movement tracing, utilizing
      the activation of caged fluorescein-dextran. This method has several advantages
      over single-cell injections in that it is rapid, allows cells at all depths in
      the embryo to be marked, can be used to follow cells starting at any time during
      development, and allows an appreciation of the movements of cells located in a
      coherent group at the time of uncaging. We demonstrate that the approach is
      effective in providing additional and complementary information on prospective
      mesoderm and brain tissues studied previously. We also present, for the first
      time, a fate map of placodal tissues including the otic vesicle, lateral line,
      cranial ganglia, lens, and olfactory epithelium. The prospective placodal cells
      are oriented at the 50% epiboly stage on the ventral side of the embryo with
      anterior structures close to the animal pole, and posterior structures nearer to
      the germ ring.

PMID- 9551180
TI  - Spatially distinct domains of cell behavior in the zebrafish organizer region.
AB  - To determine the sequence of cell behaviors that is involved in the morphogenesis
      of the zebrafish organizer region, we have examined the dorsal marginal zone of
      vitally stained zebrafish embryos using time-lapse confocal microscopy. During
      the late-blastula stage, the zebrafish dorsal marginal zone segregates into
      several cellular domains, including a group of noninvoluting, highly endocytic
      marginal (NEM) cells. The NEM cell cluster, which lies in a superficial location
      of the dorsal marginal zone, is composed of both enveloping layer cells and one
      or two layers of underlying deep cells. The longitudinal position of this
      cellular domain accurately predicts the site of embryonic shield formation and
      occupies a homologous location to the organizer epithelium in Xenopus laevis. At
      the onset of gastrulation, deep cells underneath the superficial NEM cell domain
      undergo involution to form the nascent hypoblast of the embryonic shield. Deep
      cells within the NEM cell cluster, however, do not involute during early shield
      formation, but instead move in front of the blastoderm margin to form a loose
      mass of cells called forerunner cells. Forerunner cells coalesce into a wedge
      shaped mass during late gastrulation and eventually become overlapped by the
      converging lateral lips of the germ ring. During early zebrafish tail elongation,
      most forerunner cells are incorporated into the epithelial lining of Kupffer's
      vesicle, a transient teleostean organ rudiment long thought to be an evolutionary
      vestige of the neurenteric canal. Owing to the location of NEM cells at the
      dorsal margin of blastula-stage embryos, as well as their early segregation from
      other deep cells, we hypothesized that NEM cells are specified by an early-acting
      dorsalizing signal. To test this possibility, we briefly treated early-blastula
      stage embryos with LiCl, an agent known to produce hyperdorsalized zebrafish
      embryos with varying degrees of expanded organizer tissue. In Li(+)-treated
      embryos, NEM cells appear either within expanded spatial domains or in ectopic
      locations, primarily within the marginal zone of the blastoderm. These results
      suggest that NEM cells represent a specific cell type that is specified by an
      early dorsal patterning pathway.

PMID- 9551181
TI  - Mutations resulting in transient and localized degeneration in the developing
      zebrafish brain.
AB  - In a large-scale mutagenesis screen in the zebrafish, Danio rerio, we have
      identified a heterogeneous group of 30 recessive, embryonic lethal mutations
      characterized by degeneration in the developing central nervous system that is
      either transient or initially localized to one area of the brain. Transient
      degeneration is defined as abnormal cell death occurring during a restricted
      period of development. Following degeneration, the affected structures do not
      appear to regenerate. In each case degeneration is identified after somitogenesis
      is complete and is not associated with visually identified patterning defects.
      These 30 mutations, forming 21 complementation groups, have been classified into
      four phenotypic groups: group 1, transient degeneration (13 mutations); group 2,
      spreading degeneration, early onset, in which degeneration is initially confined
      to the optic tectum but subsequently spreads to other areas of the central
      nervous system (7 mutations); group 3, late-onset degeneration, initially
      identified after 4 days (6 mutations); and group 4, degeneration with abnormal
      pigmentation (4 mutations). Although apoptotic cells are seen in the retina and
      tectum of all mutants, the distribution, temporal progression, and severity of
      degeneration vary between mutations. Several mutations also show pleiotropic
      effects, with degeneration involving extraneural structures including the
      pharyngeal arches and pectoral fins. We discuss some of the pathways important
      for cell survival in the nervous system and suggest that these mutations will
      provide entry points for identifying genes that affect the survival of restricted
      neural populations.

PMID- 9551182
TI  - Domains of retinoid signalling and neurectodermal expression of zebrafish otx1
      and goosecoid are mutually exclusive.
AB  - Retinoid signalling plays an important role in embryonic pattern formation.
      Excess of retinoic acid during gastrulation results in axial defects in
      vertebrate embryos, suggesting that retinoids are involved in early
      anteroposterior patterning. To study retinoid signalling in zebrafish embryos, we
      developed a novel method to detect endogenous retinoids in situ in embryos, using
      a fusion protein of the ligand inducible transactivation domain of a retinoic
      acid receptor and a heterologous DNA binding domain. Using this method, we show
      that retinoid signalling is localized in zebrafish embryos in the region of the
      embryonic shield, and towards the end of gastrulation in a posterior dorsal
      domain. To investigate the relationships between the spatial distribution of
      retinoid signalling and the regulation of retinoid target genes, we studied the
      downregulation by retinoic acid of two genes expressed in anterior regions of the
      embryo, goosecoid and otx1. These experiments show that expression of both genes
      is strongly downregulated in the anterior neurectoderm of zebrafish embryos
      treated with retinoic acid, whereas mesendodermal expression is only mildly
      affected. Interestingly, a significant downregulation of goosecoid expression by
      retinoic acid was observed only during midgastrulation but not in earlier stages.
      In agreement with these results, spatial expression of goosecoid and otx1 does
      not overlap with the region of retinoid signalling in the late gastrula. Our data
      support the hypothesis that a localized retinoid signal is involved in axial
      patterning during early development, at least in part through the repression of
      anterior genes in posterior regions of the embryo. Furthermore, our data suggest
      that the action of retinoids is spatially as well as temporally regulated in the
      developing embryo.

PMID- 9551183
TI  - Cross-interactions between two members of the Dlx family of homeobox-containing
      genes during zebrafish development.
AB  - The Dlx homeobox genes of vertebrates are transcribed in multiple cells of the
      embryo with overlapping patterns but often with different onsets of expression.
      Here we describe the interaction between two dlx genes, dlx3 and dlx4, during
      zebrafish development. The observation that dlx3 expression precedes that of dlx4
      in the otic vesicle led us to investigate whether dlx3 had the ability to control
      expression of dlx4. Truncated versions of dlx3 were overexpressed in zebrafish
      embryos and the expression patterns of dlx4 were examined later in development.
      Overexpression of truncated forms of Dlx3 or of a Dlx3-Dlx2 chimera was found to
      result in perturbations in dlx4 expression. In addition, cotransfection
      experiments indicated the ability of Dlx3 to activate transcription through a 1.7
      kb fragment of the 5' flanking region of dlx4. These results suggest that dlx4 is
      one of the target genes of dlx3 in embryos and that cross-regulatory interactions
      between Dlx genes may be one of the mechanisms responsible for their overlapping
      expression.

PMID- 9551184
TI  - Characterization of a cDNA encoding a novel band 4.1-like protein in zebrafish.
AB  - Membrane skeleton protein 4.1 and other members of a family of proteins that link
      the cytoskeleton to the plasma membrane may play an integral role in cell
      communication during development. The polymerase chain reaction and degenerate
      oligodeoxynucleotide primers to consensus sequences in the putative membrane
      binding domain of the protein 4.1 superfamily were used to isolate cDNAs encoding
      members of the zebrafish protein 4.1 family. Zebrafish stage- and tissue-specific
      first strand cDNA was used in the PCR. After the reaction, amplicons of the
      predicted size were sequenced to confirm their relationship to the protein 4.1
      superfamily. One cDNA, with a high degree of similarity to a mouse novel band 4.1
      like cDNA, was used to probe a zebrafish adult brain library. A 2.4-kb cDNA was
      isolated and found to encode a 619 amino acid polypeptide homologous to mouse
      novel band 4.1-like protein 4. Zebrafish nbl4 mRNA is maternally supplied and is
      expressed throughout embryogenesis. In adults, nbl4 is found in the ovary, eye,
      heart, and brain, but not in gut or skeletal muscle. When synthetic nbl4 mRNA is
      translated in vitro it binds calmodulin in a calcium-dependent manner. These data
      indicate that zebrafish nbl4 is a maternal transcript owing to its presence
      before the midblastula transition, and it is present later on in specific adult
      structures. The ability to bind calmodulin would suggest that the function of
      nbl4 protein may be potentially regulated via a calcium-calmodulin dependent
      mechanism.

PMID- 9551185
TI  - Nuclear localization signals: a driving force for nuclear transport of plasmid
      DNA in zebrafish.
AB  - Nuclear localization signals (NLSs) are short peptides required for nuclear
      transport of karyophilic proteins. We review in this paper how the nuclear
      targeting property of NLS peptides has been taken advantage of to enhance the
      efficiency of nuclear uptake of transgene DNA in zebrafish and how it may improve
      the efficiency of transgenesis in this species. Synthetic NLS peptides can bind
      to plasmid DNA by ionic interactions. Cytoplasmic injection of DNA-NLS complexes
      in zebrafish eggs enhances the rate and the amount of plasmid DNA taken up by
      embryonic nuclei. Nuclear import of DNA-NLS complexes has been duplicated in
      vitro and exhibits energetic and cytosolic requirements similar to those for
      nuclear protein import. Furthermore, binding NLSs to DNA increases expression
      frequency of the transgene. We suggest that NLS peptides may constitute a
      valuable tool to improve the efficiency of transgenesis in zebrafish and other
      species.

PMID- 9551186
TI  - Contribution of zebrafish-mouse cell hybrids to the mapping of the zebrafish
      genome.
AB  - The zebrafish, Danio rerio, is becoming an increasingly popular model for the
      study of vertebrate development. Indeed, the biology of the fish offers great
      advantages for such studies. The life cycle of the zebrafish is relatively short
      (2-3 months) and the embryos develop outside the mother, facilitating the
      visualization of any mutated phenotype. At present, more than 1000 embryonic
      mutations have been reported. However, until recently, there was no physical or
      genetic map for this organism. In an effort to generate such a map, we have
      produced and characterized a panel of zebrafish-mouse cell hybrids. We have used
      whole-cell fusion to transfer zebrafish chromosomes from two different zebrafish
      cell lines into mouse recipient cells, thus generating more than 100 hybrids.
      Using fluorescence in situ hybridization and polymerase chain reaction analysis,
      we have determined the zebrafish chromosome composition of these hybrids. Here we
      report that elements from the 25 linkage groups of the zebrafish genome are
      present in our hybrids. These hybrids could identify the chromosomal location of
      genes affected in zebrafish mutants.

PMID- 9551187
TI  - Predictive significance of magnetic resonance imaging at 4 months of adjusted age
      in infants after a perinatal neurologic insult.
AB  - The aim of this prospective study was to evaluate the predictive significance of
      magnetic resonance imaging (MRI) performed at 4 months of corrected age in 60
      neonates after a perinatal neurologic insult. Follow-up ranged from 2 to 5 years
      of chronological age. MRI examination was normal in 10; isolated external
      hydrocephalus was found in 15 infants. Twenty-three of these infants developed
      normally. Focal or multifocal lesions were shown in 6 infants, of whom 2
      developed normally. Diffuse brain involvement was present in 29 cases as atrophy
      (n = 18), leukomalacia (n = 5), basal ganglia lesions (n = 3), and delayed
      myelination (n = 3). All but 4 infants showed neurologic impairment. MRI
      performed at 4 months of adjusted age is of prognostic significance in neonates
      who suffer a moderate or mild neurologic insult.

PMID- 9551188
TI  - The production of pro- and anti-inflammatory cytokines in neonates assessed by
      stimulated whole cord blood culture and by plasma levels at birth.
AB  - The capability of neonates to achieve cytokine balance was evaluated. Production
      of the pro-inflammatory cytokines TNF alpha and IL-8, of the natural anti
      inflammatory cytokine IL10 and of the regulator of the acute phase response IL6
      was assessed after whole blood stimulation by lipopolysaccharide in cord blood (n
      = 10), adult volunteers serving as control (n = 17). Additionally, circulating
      cytokines were determined in cord and in maternal blood immediately after
      delivery (n = 27, respectively). Significant production of TNF alpha, IL8, IL10
      and IL6 was observed in cord blood after lipopolysaccharide stimulation and was
      similar to cytokine production in adult blood. The plasma concentrations of TNF
      alpha were significantly higher in cord than in maternal blood, while plasma
      concentrations of IL10 and IL6 were significantly lower. Our results demonstrate
      fully developed capability of whole cord blood to synthesize pro- and anti
      inflammatory cytokines in response to a pro-inflammatory stimulation in vitro. In
      vivo, however, higher circulating TNF alpha and lower IL10 and IL6 levels in cord
      blood suggest that the inflammatory stress associated with normal delivery does
      not induce detectable anti-inflammatory response in neonates at birth.

PMID- 9551189
TI  - The effect of phototherapy on renal blood flow velocity in preterm infants.
AB  - Mean renal blood flow velocity (RBFV) was studied with two-dimensional/ pulsed
      Doppler ultrasound and relative renal vascular resistance (RVR) was calculated
      before, during, and after phototherapy treatment in 30 preterm infants
      (gestational age < or = 32 weeks) who were treated for a minimum of 12 h with
      phototherapy for nonhemolytic hyperbilirubinemia. RBFV decreased, whereas RVR
      increased significantly after the initiation of phototherapy. In 'healthy'
      (nonventilated) infants RBFV and RVR returned to baseline values after
      discontinuation of phototherapy. Whereas in 'unhealthy' (ventilated) infants,
      RBFV and RVR did not return to baseline values after discontinuation of
      phototherapy. In 16 infants (> 50% of the cases) the ductus arteriosus reopened
      during phototherapy.

PMID- 9551190
TI  - Differential developmental effects of acute hypoxia on the rabbit
      atrioventricular conduction axis.
AB  - The differential developmental effects of hypoxia on antegrade fast and slow and
      retrograde conduction through the atrioventricular junction are unknown. This
      study describes the effects of hypoxia on fast and slow antegrade
      atrioventricular node, infra-Hisian and retrograde conduction in immature and
      mature hearts during premature pacing protocols in excise, perfused adult and
      neonatal rabbits. The results are: (1) antegrade conduction delay through the
      atrioventricular node is the same developmentally, but delay through the His
      Purkinje system is greater in adults; (2) hypoxia reduces the extra delay in the
      His-Purkinje system in adults; (3) fast atrioventricular node conduction is more
      sensitive to hypoxia in neonates than in adults, and slow atrioventricular node
      conduction is more sensitive to hypoxia in adults than in neonates, and (4)
      retrograde atrioventricular node conduction is more resistant to hypoxia in
      neonates than in adults.

PMID- 9551191
TI  - Effect of inhaled nitric oxide in endothelin-1-induced pulmonary hypertension.
AB  - The interaction of two vasoactive substances, the vasoidilator nitric oxide (NO)
      and the complex-acting peptide endothelin-1 (ET-1), may help explain the
      pathophysiology of pulmonary hypertension, an important part of many pulmonary
      disorders in neonates. To understand better the interactions of inhaled NO and ET
      1, we investigated the effects of ET-1 infusions with and without inhaled NO in
      two groups of piglets, one group pretreated with L-nitro-arginine methylester (L
      NAME) and the other not pretreated. Inhaled NO (60 ppm) was administered during
      infusion of 1.0 microgram/kg or 2.5 micrograms/kg of ET-1. In animals not
      pretreated with L-NAME, the increase in PVR and in SVR induced by either dose of
      ET-1 was not reduced with administration of NO. The increase in systemic vascular
      resistance with ET-1 was greater (mean increase of 50% above baseline with 1.0
      microgram/kg ET-1 and 100% with 2.5 micrograms/kg ET-1 by 5 min) than the
      increase in PVR, but the PVR/SVR ratio did not change during ET-1 administration.
      In contrast, animals pretreated with L-NAME did demonstrate inhibition of ET-1
      induced increase in PVR with NO. No differences in effects on SVR were noted. We
      conclude that ET-1-induced increases in PVR are not diminished by 60 ppm of
      inhaled NO unless there has been inhibition of endogenous NO production.

PMID- 9551192
TI  - Effects of intravenous infusions of noradrenaline on renal function in
      chronically catheterised fetal sheep.
AB  - To determine the effects of circulating noradrenaline on fetal renal function
      noradrenaline was infused intravenously into 7 chronically catheterised fetal
      sheep (127-138 days) at a dose (1 microgram/kg/min) which resulted in plasma
      levels similar to those which occur during hypoxia. Fetal mean arterial pressure
      increased by approximately 14 mmHg (p < 0.001) and haematocrit rose (p < 0.005).
      Glomerular filtration rate rose from 3.85 +/- 0.47 (SEM) to 4.70 +/- 0.50 ml/min
      (p < 0.05) during the first hour and fractional reabsorption of sodium by the
      proximal tubule fell (p < 0.05) during the second hour. Urine flow rate increased
      from 0.61 +/- 0.13 to 1.18 +/- 0.24 ml/min (p < 0.001) and osmolar excretion
      increased from 78 +/- 15 to 153 +/- 36 mu osm/min (p < 0.005). By contrast lung
      liquid flow fell (p < 0.05), but the increase in urine flow was much greater than
      the decline in lung liquid. These findings suggest that during hypoxia,
      noradrenaline may play an important role in the maintenance of urine flow and
      consequently amniotic fluid volume and, as suggested by others, in the
      distribution of fluid between the vascular and interstitial compartments.

PMID- 9551194
TI  - [Effect of L-glutamic acid on the reception of cytokines by HL-60 cells].
AB  - L-Glutamic acid at a concentration of 0.1 microM was found to induce
      differentiation of the cell line of HL-60 promyelocytic leukemia into
      granulocytes or neutrophils. The HL-60 cells have no specific glutamate-binding
      sites, but L-glutamic acid influences the reception of several cytokines by these
      cells. At a concentration of 0.1 microM, L-glutamic acid completely inhibits the
      high-affinity binding of 125I-labeled human recombinant interleukin-1 beta (Kd =
      0.32 nM) to the HL-60 cells, but does not affect their low-affinity binding (Kd =
      13.3 nM) and does not change the total number of the IL-1 beta-binding sites.
      Preincubation of the HL-60 cells with 0.1 microM of L-glutamic acid increases 2.5
      times the number of receptors for 125I-labeled human recombinant tumor necrosis
      factor beta. These results suggest that L-glutamic acid plays an important role
      in the differentiation of the blood myeloid cells.

PMID- 9551193
TI  - Nitric oxide modulates anoxia-induced gasping in the developing rat.
AB  - Gasping is an important mechanism for survival. Nitric oxide (NO) plays an
      excitatory role in brainstem regions mediating respiratory responses to hypoxia.
      We hypothesized that neural structures mediating anoxia-induced gasping would
      display NO dependency. Two- to 15-day-old rat pups underwent anoxic exposures
      with 100% N2 in a plethysmograph following administration of N-nitro-L-arginine
      methyl ester (L-NAME), a nitric oxide synthase (NOS) blocker, L-arginine (L-Arg),
      a NO precursor, or normal saline. In general, gasp latencies were significantly
      shorter after L-Arg, and were prolonged with L-NAME. Furthermore, NOS inhibition
      prolonged gasping duration and reduced gasping frequency at all postnatal ages,
      although this effect was particularly increased with advancing postnatal age.
      NADPH-diaphorase staining and Western blots of protein lysates from the lateral
      tegmental field, the putative neural center underlying gasp generation, revealed
      progressively increased neuronal NOS abundance with animal maturation. We
      conclude that anoxia-induced gasping neurogenesis is modulated by NO mechanisms
      in neonatal pups. We postulate that higher NO brainstem concentrations may favor
      early autoresuscitation but be detrimental to overall survival during prolonged
      asphyxia.

PMID- 9551195
TI  - [Synthesis of new chromogenic substrates for aspartyl proteases].
AB  - A general method was developed for the synthesis of new chromogenic substrates of
      aspartyl proteases: Dnp-Ala-Xaa-Phe-Phe-Ala-Arg-NH2, where Xaa was Ala or Ser.
      The synthetic scheme involved both chemical and enzymic stages, the condensation
      of tripeptides in an organic medium by means of pepsin immobilized on Celite
      being among the latters. The influence of organic solvents, reaction time, and
      the composition and ionic strength of the buffers used in the reaction mixture
      and at the pepsin immobilization step on the efficacy of the pepsin-catalyzed
      synthesis was studied.

PMID- 9551196
TI  - [Acyclic nucleotide analogues based on phosphonic acids].
AB  - The synthesis of novel nucleotide analogues on the basis of ethylphosphonic acid
      was described. A rigid structural element, an amide or a double bond, was
      characteristics of the compounds synthesized. The antiviral and cytotoxic
      activities of these compounds were studied in cell cultures.

PMID- 9551198
TI  - [Interaction of short oligonucleotide derivatives with nucleic acids. V. Ligation
      of short oligonucleotides in tandem on a complimentary DNA template].
AB  - A tetranucleotide was highly specifically and quantitatively ligated with a pair
      of flanking octanucleotides carrying both radioactive and nonradioactive reporter
      groups. The sequence of the ligation of oligonucleotide components in a tandem on
      a complementary template was studied. The first stage was found to be the enzyme
      catalyzed activation of the phosphate group of octanucleotide, a tandem component
      that possesses a higher hybridization capacity than the tetramer. It is shown
      that the introduction of terminal reporter groups into octanucleotides does not
      decrease the efficiency of their tandem ligation.

PMID- 9551197
TI  - [Phosphorylation of 5'-O-phosphonylmethylthymidine and its incorporation into
      HeLa cells DNA].
AB  - [3H]5'-O-Phosphonylmethylthymidine with a specific activity of 71 Ci/mmol was
      obtained by isotope exchange. Its incubation with a HeLa cell culture resulted in
      the formation of [3H]-labeled 5'-O-(beta-phosphoryl-alpha
      phosphonylmethyl)thymidine, 5'-O-(beta,gamma-diphosphoryl-alpha
      phosphonylmethyl)thymidine, and [3H]DNA. This proved the ability of 5'-O
      phosphonylmethylthymidine to undergo phosphorylation and incorporation into the
      DNA of human cells.

PMID- 9551199
TI  - [Interaction of short oligonucleotides derivatives with nucleic acids. VI.
      Discrimination of mismatch-containing complexes upon ligation of a short
      oligonucleotide tandem on DNA template].
AB  - The high ligation specificity of a tetranucleotide with a pair of flanking
      octanucleotides on DNA template by the action of T4 phage DNA ligase is shown. In
      a tetranucleotide-DNA template complex containing a mismatch, almost no ligation
      products are formed. The ligation of a tandem octanucleotide-tetranucleotide
      octanucleotide makes it possible to identify accurately any single nucleotide
      substitution in a tetranucleotide binding site.

PMID- 9551200
TI  - [Irregular temperature dependence of the efficiency of nucleic acids site
      directed modification by oligonucleotide reagents producing reactive
      intermediates].
AB  - A 22-mer target DNA pTGCCTGGAGCTGCTTGATGCCC (I) was modified by a
      dodecadeoxyribonucleotide reagent GCATCAAGCAGCp[N(CH3)CH2RCl] (II) containing a
      3'-terminal alkylating group (RCl = -C6H4N(CH3)(CH2CH2Cl). An anomalous, bell
      shaped temperature dependence of the maximum extent of the modification was
      found. Based on the analysis of the kinetic scheme of the modification, a
      possible explanation for this experimental fact is given.

PMID- 9551201
TI  - [Exon-intron structure of the fet5+ gene of Schizosaccharomyces pombe and
      physical mapping of genome encompassing regions].
AB  - Plasmid pYUK3 bearing the fet5+ gene of Schizosaccharomyces pombe was isolated
      from a genomic library of the fission yeast, and a detailed physical map of the
      whole genomic insert (ca. 9.6 Kbp) was constructed. The primary structure of the
      fet5+ gene and its flanking regions is established. The gene contains a single 45
      bp intron in its distal part. A typical TATA-box (TATAAG) was found in the 5'
      noncoding region ca. 50 bp upstream of the putative start of transcription, and
      the 3'-noncoding region contains AT-rich palindromes, which are probably involved
      in termination of the fet5+ transcription. A previously unidentified gene of Sz.
      pombe encoding a protein with some similarity to one of the transcriptional
      activators from the TBP (TATA-binding protein) group of SPT factors of
      transcription was found in the vicinity of the fet5+ gene. Taking into account
      that cDNA of the fet5(+)-gene was isolated as a suppressor of the genetic-defect
      of nuclear RNA polymerases I-III (Bioorg. Khim., 1997, vol. 23, No 3, pp. 234
      237), this vicinity may be the first evidence of possible clustering, in the
      genome of the fission yeast, of genes participating in transcription regulation.

PMID- 9551202
TI  - [Expression of synthetic human interleukin-10 gene and its mutant variants in
      Escherichia coli cells].
AB  - The human interleukin-10 gene was obtained by chemico-enzymatic synthesis, and
      vectors for cytoplasmic and periplasmic expression of the recombinant IL-10 gene
      in Escherichia coli cells were constructed. Mutant IL-10 genes bearing
      substitutions in a region upstream of the ATG codon and in the triplet coding for
      the second amino acid residue in the protein were obtained by in vitro
      mutagenesis. High levels of expression were observed for the fusion protein
      composed of IL-10 and an N-terminal fragment of IL-3 and for the mutant IL-10
      containing cysteine as the second amino acid residue.

PMID- 9551203
TI  - [Synthesis and biological properties of 3,5-cyclophosphates- and -amidophosphates
      of 1,2-O-alkylydene-6-deoxy-6-halogeno-alpha -D-glucofuranoses].
AB  - 3,5-Cyclic phosphates and phosphoramides of 6-halogenated glucofuranoses were
      synthesized via interaction of 3,5,6-bicyclophosphites of 1,2-O-alkylidene-alpha
      D-glucofuranoses with halogens (followed by treatment with nucleophilic reagents)
      and N-chloroamines. 3,5-Cyclic trans-dibutylphosphoramides of 6-chloro-6-deoxy
      1,2-O-isopropylidene- and 6-chloro-6-deoxy-(R)-(2,2,2)-trichloroethylidene)-alpha
      D-glucofuranoses were shown to possess antiproliferative activity against CaOv
      human ovarian carcinoma cells in vitro (CE50 of approximately 10(-5) M). Cyclic
      trans-dibutylphosphoramide of 6-chloro-6-deoxy-1,2,-O-isopropylidene-alpha-D
      glucofuranose also displayed marked antitumor effect on P-388 transplantable
      murine leukemia in vivo (the maximum increase in life span of 100% was reached at
      the quintuple injection of 100 mg/kg daily).

PMID- 9551204
TI  - [Synthesis of phthalocyanine conjugates with monoclonal antibodies in AOT/n
      octane reversed micelles and in water-organic solvent mixtures].
AB  - Conjugates of cobalt and aluminum phthalocyanines with monoclonal antibodies were
      synthesized using an AOT/n-octane reversed micellar system or water-organic
      mixtures with a low content of organic solvent as media. The effect of the degree
      of hydration of the micelles and the concentration of phthalocyanines on the
      composition of conjugates was studied. The immune activity of the resulting
      conjugates in comparison to that of native antibodies was evaluated. The
      catalytic activity of free cobalt phthalocyanines and their antibody conjugates
      was studied in the reaction of ascorbic acid oxidation.

PMID- 9551205
TI  - [New putative gene from human retrovirus-containing locus on chromosome 19].
AB  - By means of cDNA selection, a cDNA clone corresponding to a putative gene was
      isolated. The identified gene was mapped to human chromosome 19 (region 19q12) to
      the locus containing the human endogenous retrovirus HERV-K LTR. The distance
      between the LTR and the cDNA fragment is about 20 kb. RT-PCR analysis of the
      total RNA revealed that the corresponding gene is preferentially expressed in the
      brain.

PMID- 9551206
TI  - Antimetabolites.

PMID- 9551207
TI  - Bleomycin.

PMID- 9551208
TI  - Mitomycins.

PMID- 9551209
TI  - Taxanes.

PMID- 9551210
TI  - DNA topoisomerase I inhibitors.

PMID- 9551211
TI  - DNA topoisomerase II poisons and inhibitors.

PMID- 9551212
TI  - Cisplatin.

PMID- 9551213
TI  - Multidrug resistance.

PMID- 9551215
TI  - Monoclonal antibody therapy of cancer.

PMID- 9551214
TI  - New anticancer agents.

PMID- 9551216
TI  - Cytokines and immunological monitoring.

PMID- 9551217
TI  - Biological response modifiers.

PMID- 9551218
TI  - Adoptive immunotherapy.

PMID- 9551219
TI  - Strategies for cancer gene therapy.

PMID- 9551220
TI  - Retinoids, neoplasia and differentiation therapy.

PMID- 9551221
TI  - Hematopoietic growth factors in cancer chemotherapy.

PMID- 9551222
TI  - Leukemias and plasma cell myeloma.

PMID- 9551223
TI  - AIDS-related malignancies.

PMID- 9551224
TI  - Head and neck cancer.

PMID- 9551225
TI  - Lung cancer.
AB  - In small cell lung cancer (SCLC) combination chemotherapy including agents such
      as etoposide, teniposide, cisplatinum, carboplatin, and vincristine, doxorubicin,
      and cyclophosphamide, or ifosfamide continues to be the back-bone of therapy. The
      epipodophyllotoxin derivatives together with cisplatin or carboplatin are being
      used increasingly as part of the initial therapy, and these combinations are by
      most investigators considered standard therapy. Complete plus partial responses
      to combination therapy occur in 80-90% of all patients with a median duration of
      9-12 months. The median survival in these studies is at present 11-18 months
      depending on the initial tumour stage. The 5-year survival data remain still
      around 5% including a small fraction of patients (2%) initially presenting with
      extensive disease. The tendency is to shorten the duration of treatment to 5-8
      months. The results of intensifying the treatment with the use of haematopoietic
      growth factors continue to be disappointing, although these are not conclusive.
      With respect to squamous cell carcinoma, adenocarcinoma, and large cell carcinoma
      several meta-analyses indicate that there is a statistically significant, albeit
      small advantage favouring cisplatinum containing chemotherapy when added to
      surgery in stage I and II disease and to radiotherapy in stage III NSCLC.
      Similarly, cisplatin containing chemotherapy is statistically superior to best
      supportive care in stage IV disease. The results from the latter analyses are
      significant at 1 and 2 years, respectively, but not at 3 and 5 years of survival.
      These data must, however, be considered in the light of their clinical relevance
      and of the balance between quality of life, toxicity, and cost of chemotherapy.
      The results of recently published phase III trials in stage III disease support
      the use of combined modalities of chemotherapy and radiotherapy versus
      radiotherapy alone. For both small cell and non-small cell lung cancer a number
      of new agents have been evaluated over the last 2 to 3 years and among those
      navelbine, topotecan, gemcitabine, and taxanes (taxol and taxotere) have yielded
      the most encouraging results. For mesothelioma the therapeutic results are
      unchanged, and no standard chemotherapy has yet been developed.

PMID- 9551226
TI  - Upper gastrointestinal tumors.

PMID- 9551227
TI  - Cancers of the large bowel and hepatobiliary tract.

PMID- 9551228
TI  - Endocrine tumours.

PMID- 9551229
TI  - Genitourinary malignancy.

PMID- 9551230
TI  - Gynecologic cancers.
AB  - In conclusion, significant advances have been made in ovarian cancer.
      Specifically, these relate to the success of paclitaxel and platinum-based
      regimens. The appropriate scheduling, dosing, and the selection of carboplatin vs
      cisplatin remains controversial. The role of interval debulking surgery is still
      investigational and we remain cautiously optimistic as to its long-term benefit.
      The progress in the delivery of chemotherapy to patients with cervical carcinoma,
      endometrial carcinoma, vaginal carcinoma, and vulvar carcinoma has been slowed by
      the paucity of prospective-randomized trials. Although numerous single
      institution non-randomized trials show promising regimens, they lack significant
      power and appropriate study design to prove meaningful. Our goals in the future
      should be to try to enter most of these patients into national collaborative
      studies where significant conclusions can be made because of appropriate study
      design and adequate patient numbers.

PMID- 9551231
TI  - Breast cancer.

PMID- 9551232
TI  - Soft tissue and bone sarcomas.

PMID- 9551233
TI  - Brain tumors.

PMID- 9551234
TI  - Biology and treatment of pediatric malignant solid tumors.

PMID- 9551235
TI  - Supportive care.

PMID- 9551236
TI  - In vitro activity of enoxacin versus ciprofloxacin, fleroxacin, lomefloxacin,
      ofloxacin, pefloxacin, and rufloxacin against uropathogens.
AB  - Minimum inhibitory concentrations (MIC) of enoxacin, ciprofloxacin, fleroxacin,
      lomefloxacin, ofloxacin, pefloxacin and rufloxacin were determined against 400
      uropathogens cultured from the urine of patients with complicated and/or hospital
      acquired urinary tract infections (UTI) using an agar dilution method. The
      bacterial spectrum consisted of Entero-bacteriaceae (34.5%), enterococci (31.5%),
      staphylococci (21.2%) and non-fermenting bacteria (12.8%). Enoxacin inhibited all
      but one strain (Enterobacter cloacae) of Enterobacteriaceae up to an MIC of 1
      mg/l (MIC90 0.25 mg/l). Regarding the total bacterial spectrum, enoxacin
      inhibited 54.5, 59.5, 76.0 and 83.8% up to an MIC of 1, 2, 4 and 8 mg/l,
      respectively. If the same breakpoint of resistance for ofloxacin according to DIN
      58,940 (NCCLS), i.e. MIC > or = 4 mg/l (> or = 8 mg/l), is also taken for the
      other fluoroquinolones, and the 126 strains of enterococci are excluded, for
      which alternative agents, e.g. aminopenicillins, should be considered instead,
      the following resistance rates were found: ciprofloxacin and enoxacin 15.3%
      (15.0%), ofloxacin 17.2% (15.3%), pefloxacin 18.2% (15.3%), fleroxacin 19.3%
      (15.3%), lomefloxacin 19.7% (17.9%) and rufloxacin 31.8% (27.4%). According to
      their in vitro activity, all fluoroquinolones tested besides rufloxacin show
      similar rates of resistance against uropathogens and can therefore be considered
      good alternative agents for the treatment of complicated UTI.

PMID- 9551238
TI  - In vitro interaction between ofloxacin and cefotaxime against gram-positive and
      gram-negative bacteria involved in serious infections.
AB  - The checkerboard method was used to determine the antimicrobial activity of the
      combination cefotaxime/ofloxacin against 217 bacterial isolates involved in
      serious infections. Synergy or partial synergy was observed against 19 of 34
      (55.8%) Staphylococcus aureus methicillin-susceptible isolates, 4 of 47 (8.4%)
      Streptococcus pneumoniae isolates, 28 of 34 (82.2%) Escherichia coli isolates and
      70 of 102 (68.5%) Pseudomonas aeruginosa isolates. Antagonism was not observed
      with any of the isolates examined.

PMID- 9551237
TI  - In vitro antibacterial activity of trovafloxacin and five other fluoroquinolones.
AB  - The in vitro inhibitory and bactericidal activities of the investigational
      fluoroquinolone trovafloxacin were studied and compared with those of five other
      fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin, rufloxacin and
      sparfloxacin) against a wide range of clinical isolates from Italian hospitals.
      Against gram-positive bacteria, trovafloxacin was overall more active than the
      other antibiotics tested, including sparfloxacin, another gram-positive-oriented
      fluoroquinolone, and was active against all ciprofloxacin-resistant streptococci,
      enterococci, and listeriae, all ciprofloxacin-resistant Staphylococcus aureus
      isolates and most ciprofloxacin-resistant coagulase-negative staphylococci. Its
      antistaphylococcal activity was not affected by oxacillin resistance or
      susceptibility of the isolates, nor was its antipneumococcal activity affected by
      whether isolates were susceptible or resistant to penicillin. Against gram
      negative bacteria, trovafloxacin retained a high potency mostly comparable with
      that of ciprofloxacin. Rufloxacin and pefloxacin were less active than the other
      fluoroquinolones against most test strains of both gram-positive and gram
      negative organisms. Trovafloxacin minimal bactericidal concentrations usually
      equalled or exceeded by 2-4 times the minimal inhibitory concentration values,
      indicating that the compound is overall highly bactericidal.

PMID- 9551239
TI  - Therapeutic effects of an injectable new quinolone, pazufloxacin, against
      polymicrobial infections in the uterine endometritis model.
AB  - Polymicrobial infections with aerobes and anaerobes are common in female genital
      tract infections. We evaluated the efficacy of an injectable new quinolon,
      pazufloxacin, using a uterine endometritis model. Rats were infected with a mixed
      inoculation of Escherichia coli plus Bacteriodes fragilis (MIC of pazufloxacin
      and ceftazidime: E. coli: 0.05 and 1.56 micrograms/ml, respectively, B. fragilis:
      3.13 and 3.13 micrograms/ml, respectively). After inoculating 10(7) cfu/rat of
      each organism, pazufloxacin or ceftazidime (10 or 20 mg/kg, respectively, i.v.,
      b.i.d., 3 days) was administered and compared with the nontreated group. The
      viable cell counts of the uterine corpus and uterine cervix in pazufloxacin
      treated and ceftazidime-treated groups were decreased, compared with the
      nontreated group. The viable cell counts of the adnexa in the pazufloxacin
      treated group were significantly decreased, compared with the ceftazidimetreated
      group. These results suggest that pazufloxacin would be useful for the treatment
      of polymicrobial infections, especially adnexitis.

PMID- 9551240
TI  - Therapeutic effects of cefozopran on polymicrobial infections associated with
      Enterococcus faecalis in a Rat pyometra model.
AB  - Enterococcus faecalis plays an important role as a pathogen in polymicrobial
      infections. We evaluated the efficacy of cefozopran (CZOP) using polymicrobial
      pyometra rats. Rats were infected with a mixed intrauterine inoculation of E.
      faecalis plus either Bacteroides fragilis or Prevotella bivia (minimal inhibitory
      concentration of CZOP; E. faecalis: 6.25 micrograms/ml, B. fragilis: 12.5
      micrograms/ml, P. bivia: 12.5 micrograms/ml). Immediately after inoculating 10(5)
      CFU of each organism/rat, CZOP (either 40 mg/kg, i.v., q.i.d., for 5 days or 80
      mg/kg, i.v., b.i.d., for 5 days) was administered. The intrauterine inflammatory
      change and bacterial counts in the CZOP-treated group were compared with those in
      the nontreated control group. CZOP significantly (p < 0.01) decreased the
      bacterial counts except for B. fragilis in the regimen of 80 mg/kg b.i.d.
      However, the 40 mg/kg, q.i.d., regimen significantly (p < 0.05) reduced bacterial
      counts compared to 80 mg/kg, b.i.d. These results suggest that CZOP in a more
      divided dose is efficacious for the treatment of polymicrobial infections
      associated with E. faecalis in pyometra.

PMID- 9551241
TI  - Evaluation of different antibiotics in inhibiting colonization of Vibrio cholerae
      O1 and O139 in the rabbit intestine.
AB  - The effects of furazolidone, erythromycin and azithromycin in inhibiting
      colonisation of Vibrio cholerae O1 and O139 in the rabbit intestine were tested.
      Both V. cholerae O1 and O139 highly colonised the gut in control rabbits. The
      colonisation of furazolidone-resistant strains in the rabbit intestine was
      prevented effectively by both erythromycin and azithromycin. In furazolidone
      sensitive strains, the efficacies of erythromycin and azithromycin were very much
      comparable to furazolidone. These results suggested that azithromycin may be
      subjected to clinical trial in comparison to furazolidone and erythromycin for
      the treatment of cholera due to O1 and O139 infection in children.

PMID- 9551242
TI  - Antifungal activity of D0870 against murine infections and its mechanism of
      action.
AB  - We evaluated the in vivo antifungal activity of D0870, a new triazole agent, in
      comparison with that of fluconazole in two murine infection models. The
      therapeutic mechanism of D0870 in these models was also investigated in vitro. In
      a pulmonary infection with Cryptococcus neoformans in immunosuppressed mice,
      D0870 at 10-100 mg/kg significantly reduced viable counts in lungs infected with
      C. neoformans to 1/10-1,000 of the control on day 14, whereas fluconazole, only
      at 100 mg/kg, showed a significant reduction in the viable counts and was less
      active than D0870 at 10 mg/kg. D0870 at 3-30 mg/kg also showed excellent
      therapeutic efficacy against murine vaginal candidiasis and completely eliminated
      viable yeasts from the vaginal cavity, whereas positive cultures were found in
      20% of mice treated with 30 mg fluconazole/kg. At pH 7 and 37 degrees C, D0870
      was active against C. neoformans in synthetic amino acid medium, fungal or
      sabouraud dextrose broth. By reducing the pH of the medium, the in vitro
      anticryptococcal activity of D0870 was enhanced and found to be fungicidal under
      all culture conditions at pH 4-5. D0870 also showed a stronger fungistatic
      activity against Candida albicans at pH 4. These results suggest that D0870 may
      exhibit a potent activity against these two murine infections by exerting an
      excellent antifungal activity at the infection sites thought to be acidic
      environments.

PMID- 9551243
TI  - A comparative study of the cytogenetic and antineoplasmatic effects induced by
      carboplatin in combination with niacin in human lymphocytes in vitro and in
      Ehrlich ascites tumor cells in vivo.
AB  - Enhanced sister chromatid exchange (SCE) levels and cell division delays were
      observed when cultured human lymphocytes treated with carboplatin (cPt) were
      exposed to niacin. Cytogenetic damage was also observed by cPt when Ehrlich
      ascites tumor (EAT) cells were exposed in vivo to nontoxic concentrations of
      niacin. One hour before intraperitoneal injection of 5-bromodeoxyuridine,
      adsorbed to activated charcoal, EAT-bearing mice treated intraperitoneally with
      cPt appeared to have a dose-dependent increase in SCEs and cell division delays.
      Niacin increased the survival time of the EAT-bearing mice treated with cPt and
      markedly reduced the ascitic volume. Therefore the in vivo antitumor effect of
      cPt in conjunction with niacin appears to correlate well with the in vitro or in
      vivo synergistic effects on cytogenetic damage caused by the combined cPt plus
      Niacin treatment upon human lymphocytes or EAT cells, respectively.

PMID- 9551245
TI  - Once-daily use of ofloxacin for prophylaxis in breast cancer surgery.
AB  - The 150 consecutive patients who were hospitalized for breast cancer at our
      department between September 1992 and November 1995 were enrolled in this open
      study after having given their informed consent. Patients were assigned randomly
      to receive ofloxacin in daily doses of 200 mg to be taken in a single dose or a
      total dose of 600 mg divided into three doses postoperatively for 5 days. Ten
      patients (8 found to be without malignancies) were excluded from evaluation.
      Wound infections developed in 8 (12%) of the 69 patients in the 200-mg group and
      12 (17%) of the 71 patients in the 600-mg group. Postoperative wound care lasted
      a median of 19 days (25th and 75th percentiles, 15 and 29 days) for patients
      given 200 mg and 16 days (13 and 25 days) for those given 600 mg; the difference
      was not statistically significant (Wilcoxon's U test). Signs or symptoms
      suggesting ofloxacin toxicity were not observed, and several significant
      differences were found in laboratory test results between the two groups both
      before and after treatment. Abnormal changes after treatment were found in many
      individuals, but the rate of occurrence was similar in the two groups (U test).
      When ofloxacin is used for prophylaxis after breast surgery, we recommend a once
      daily administration of 200 mg orally for financial reasons and increased patient
      compliance.

PMID- 9551246
TI  - Prospective comparison of ceftriaxone and cefotaxime for the short-term treatment
      of bacterial meningitis in children.
AB  - The effectiveness and safety of ceftriaxone and cefotaxime in the short-term
      treatment of primary bacterial meningitis were compared using a prospective,
      randomized, multicenter study design. Children between the ages of 6 weeks and 16
      years received either ceftriaxone as a single dose (100 mg/kg on the first day
      followed by 75 mg/kg/day) or cefotaxime as four divided doses (200 mg/kg/day) for
      4-7 days. A total of 82 patients (44 ceftriaxone, 38 cefotaxime) with documented
      bacteria in the CSF were studied. In patients receiving ceftriaxone, full
      recovery occurred in 79.5% while a further 13.7% recovered with neurologic
      sequelae. Full recovery was observed in 71.1% of children treated with cefotaxime
      with sequelae in a further 23.6% (no statistically significant differences
      between drugs). The time to clinical improvement and resolution of fever (3-4
      days) was also similar for both drugs. All but 1 of the 82 patients studied had
      negative CSF cultures within 24 h of the beginning of therapy consistent with the
      excellent penetration into the CSF (trough concentrations of 2.7 mg/l for both
      drugs at the end of therapy). No differences were observed in the incidence of
      clinically significant adverse events. Ceftriaxone and cefotaxime are both
      effective in the treatment of bacterial meningitis. Ceftriaxone offers an
      advantage in case of administration since it is administered as a single daily
      dose.

PMID- 9551244
TI  - Paclitaxel is an effective antiproliferative agent on the human NCI-H295
      adrenocortical carcinoma cell line.
AB  - In view of a potential clinical use, we assessed the antiproliferative effect of
      paclitaxel on the human steroid-secreting NCI-H295 adrenocarcinoma cell line. By
      MTT, paclitaxel induced a dose-dependent inhibition of cell proliferation, with
      IC50 lower than blood levels of the drug achieved in patients treated for other
      malignancies. Cell exposure to paclitaxel for 24 h at the different IC50S
      produced a dose-responsive increase in DNA fragmentation, morphologically
      confirmed by electron microscopy. A time-dependent decrease in aldosterone,
      cortisol and testosterone was observed. Paclitaxel is an effective
      antiproliferative agent in this human adrenocortical carcinoma cell line.
      Apoptosis induced by the drug in involved in neoplastic cell death. A potential
      role of the drug in the treatment of patients with adrenocortical cancer could be
      considered.

PMID- 9551247
TI  - Neuroendocrine signals in the regulation of gonadotropin-releasing hormone
      secretion.
AB  - Gonadotropin-releasing hormone (GnRH) is a key hypothalamic peptide that controls
      the secretion of pituitary gonadotropins, particularly luteinizing hormone (LH),
      and hence gonadal function. Hypothalamic GnRH is released in a pulsatile manner.
      In the female, the pattern of GnRH pulses, i.e., pulse frequency and amplitude,
      varies during different reproductive stages and among different species. Several
      central and peripheral signals modulate GnRH neuronal activities. Some of these
      signals are stimulatory to GnRH release, e.g., norepinephrine (NE) and
      neuropeptide Y (NPY); some are inhibitory, e.g., beta-endorphin and interleukin
      1; others are both stimulatory and inhibitory, e.g., estradiol-17 beta (E2). The
      neuronal structures and chemical interactions that result in pulsatile GnRH
      release remain unresolved. However, the core of the so-called 'GnRH pulse
      generator' likely involves NE and NE transporter (NET, the protein for pre
      synaptic re-uptake of NE). Both secretion and re-uptake of NE may determine
      hypothalamic NE availability. Many of the GnRH-stimulating and GnRH-inhibiting
      signals may influence the 'pulse-generator' by acting on GnRH neurons as second
      level signals. Hypothalamic GnRH is also released in a "surge" manner that is
      triggered either by increasing levels of circulating steroids (E2 and
      progesterone) during the preovulatory period in spontaneous-ovulating species, or
      by coitus in induced-ovulating animals. The sequential steps and mechanisms by
      which the GnRH surge occurs after E2 or coitus are not clear. However, it is
      unlikely that the E2 or coital stimuli act directly on GnRH neurons; E2 receptors
      have not been found in GnRH cells whereas coital signals must stop in the
      brainstem before they reach the hypothalamus. The brainstem may be an extra
      hypothalamic site where both E2 and coital stimuli are transformed into GnRH
      stimulating signals. One such signal may be NE whose brainstem cell bodies send
      terminals into the hypothalamus. Evidence from our laboratory suggests that a
      hypothalamic NE surge occurs at the time of the preovulatory GnRH surge in both
      the monkey and rabbit. Moreover, gene expression of both tyrosine hydroxylase
      (the rate-limiting enzyme for NE synthesis) and NET (the rate-limiting factor for
      synaptic NE transmission) in the brainstem increases after E2 in the monkey and
      after coitus in the rabbit. Other hypothalamic and/or brainstem signals, i.e.,
      NPY, galanin, beta-endorphin, nitrous oxide and gamma aminobutyric acid, are
      likely involved in generating, maintaining and/or modulating the GnRH surge
      process. A better understanding of the up-stream GnRH-regulating signals will
      help improve treatments for many reproductive disorders associated with stress,
      obesity, infection and aging.

PMID- 9551248
TI  - The endocrine mechanism of sex reversal in the protandrous black porgy,
      Acanthopagrus schlegeli: a review.
AB  - Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite,
      is a functional male for the first 2 years of life but begin to sexually reverse
      to female after the third year. This sex pattern provides a very good model to
      study the mechanism of sex reversal in fish. The gonad at 5 month of age
      consisted of testicular tissue with few primary oocytes at 5 month of age. The
      ovarian tissue became dominant at 18 months of age during the non-spawning
      season. Testicular and ovarian tissues were separated by connective tissue.
      Plasma estradiol-17 beta(E2), vitellogenin and 11-ketotestosterone (11-KT)
      profiles in males were significantly different from those in the 3-year-old
      reversing females. Peak levels of plasma E2 in the reversing females occurred
      during the early prespawning season (in October). Lower levels of plasma E2 were,
      however, observed in the males. Plasma 11-KT levels significant decreased but no
      changes of plasma testosterone were detected in the reversing females. Exogenous
      E2 suppressed the testicular development but induced the gonadal aromatase
      activity, ovarian development and sex reversal in 2-year-old black porgy.
      Exogenous T and LHRH analog did not have effects on the sex reversal. Higher
      concentrations of pituitary GtH II and mRNA of GtH II-beta subunit were detected
      in the reversed females. These data suggested that E2 and gonadal aromatase
      closely associated to the occurrence of sex reversal. A working model of the sex
      reversal in black porgy is proposed.

PMID- 9551249
TI  - Abnormal gonadotropin release and carbohydrate metabolism in morbid obese women.
AB  - Obese women are associated with clinical symptoms suggestive of abnormal
      reproductive functions including irregular menses and infertility. Previous
      studies of gonadotropin release in obese women, basal or after luteal hormone
      releasing hormone (LHRH) stimulation, are controversial. Obese women are also
      often characterized by glucose intolerance and hyperinsulinemia which might
      relate to their excessive body fat. To understand the link between abnormal
      gonadotropin release, carbohydrate metabolism and percent body fat, we examined
      17 premenopausal morbid obese women with body mass index (BMI) 38.7 +/- 1.6 Kg/m2
      (mean +/- SEM) and 16 age-matched lean controls with BMI 19.7 +/- 0.6 Kg/m2.
      Plasma glucose, insulin and C-peptide values were measured before and 30, 60, 90
      and 120 min after a 75 gm oral glucose tolerant test (OGTT). Each individual also
      received LHRH test which involved determinations of serum LH and FSH values at
      basal, 15, 30 and 60 min after injection of LHRH for 0.1 mg intravenously. Women
      with morbid obesity had significantly greater responses of glucose, insulin and C
      peptide values as compared with lean women (all p < 0.001, two-way ANOVA).
      Despite that basal concentrations were not different, serum LH, FSH and ratio of
      LH to FSH values in response to LHRH test showed significantly lesser increase in
      obese women than lean controls. Percent body fat, determined by bioelectrical
      impedance analysis, correlated positively with plasma glucose, insulin and C
      peptide responses to OGTT while negatively with ratio of LH to FSH responses (r =
      -0.418, p < 0.01) to LHRH test. Body mass index also correlated inversely with
      ratio of LH to FSH responses (r = -0.472, p < 0.01). In conclusion, morbid obese
      women had glucose intolerance, hyperinsulinemia and lower responses of serum LH
      and FSH values as compared with lean women. Excessive body fat play an important
      role in mediating these carbohydrate and gonadotropin abnormalities.

PMID- 9551250
TI  - 17 beta-estradiol-induced increases in glucose-regulated protein 78kD and 94kD
      protect human breast cancer T47-D cells from thermal injury.
AB  - Heat shock alters the susceptibility of tumor cells to chemotherapeutic agents.
      We conducted experiments to study the regulation of expression of heat shock
      proteins (HSP) in 17 beta-estradiol-treated T47-D cells, a human breast cancer
      cell line. Cells exposed to 17 beta-estradiol for 24-48 h displayed increased
      expression of glucose regulated protein 78kD (GRP-78) and 94kD (GRP-94), as shown
      by [35S]methionine incorporation and Western blotting experiments. The increase
      was time (5 h to 48 h)-dependent at 1 nM and 1 microM 17 beta-estradiol. Cells
      overexpressing GRP-78 and -94 after treatment with 17 beta-estradiol displayed
      resistance against heat shock (47 degrees C for 50 min)-induced death. Removal of
      external Ca2+ or treatment of cells with BAPTA (a Ca2+ chelator) did not alter
      the synthesis of GRP-78 and -94, suggesting that the 17 beta-estradiol effect on
      the synthesis of GRP-78 and -94 is Ca(2+)-independent. In addition, exposure of
      cells to 17 beta-estradiol up to 100 microM did not increase [Ca2+]i, which
      further supports the view that the estrogen-induced GRPs are not regulated by
      [Ca2+]i. Treatment with H89 (a protein kinase A inhibitor, 1 microM, 30 min) or
      GF-109203X (a protein kinase C inhibitor, 1 microM, 30 min) also did not change
      the GRP synthesis, indicating that protein kinase A and C are not involved in
      regulation of GRP synthesis.

PMID- 9551251
TI  - Interaction between triiodothyronine and ovarian steroid hormones on the
      regulation of the release of thyrotropin and thyrotropin-releasing hormone in
      vitro.
AB  - In vivo and in vitro experiments were designed to examine [1] the effect of
      triiodothyronine (T3) and/or ovarian steroids on the spontaneous and thyrotropin
      releasing hormone (TRH)-stimulated release of thyrotropin (TSH) by the anterior
      pituitary gland (AP) in vitro; and [2] the in vivo effects of T3 and ovarian
      steroids on TRH-release in vitro. In the experiment 1, ovariectomized
      thyroidectomized (Ovx-Tx) rats were injected with triiodothyronine (T3, 2
      micrograms/kg), estradiol benzoate (EB, 25 micrograms/kg), progesterone (P, 10
      mg/kg), T3 plus EB, T3 plus P, EB plus P, or T3 plus EB and P for 6 days before
      decapitation. The AP was incubated with Locke's medium, challenged with TRH (30
      nM), recovered and then with T3 (10 nM) only or with T3+TRH, 30 min for each
      interval. Mediobasal hypothalami (MBHs) were challenged with high potassium (60
      mM) for 30 min. In the experiment 2, the APs of Ovx-Tx rats were enzymatically
      dispersed and the AP cells were pretreated with or without EB (0-6 nM) for 72 h,
      and further with T3 (10 nM) for 24 h, followed by an incubation for 30 min with
      TRH (0-100 nM). The spontaneous and TRH-induced release of TSH in vitro from rat
      APs, and pituitary TSH content were increased by T3, or T3 plus P as compared
      with the animals injected with vehicle, or P alone. EB inhibits the effect of T3
      on TSH release in vitro. Application of T3 in vitro prevented the release of TSH
      in response to TRH. EB dose-dependently relieved the inhibitory effect of T3 on
      TRH-induced TSH release in vitro. TRH release from MBH was increased by EB and
      inhibited by T3 or P. EB prevented the inhibitory effect of T3 on TRH release. P
      plus T3 potentiated the stimulatory effects of EB on TRH release. These results
      suggest that [1] the reduction of the concentration of plasma TSH by T3 is at
      least in part due to the inhibitory effects of T3 on TRH release from mediobasal
      hypothalamus, and TSH release in response to TRH, [2] the increased content and
      release of TSH from rat AP tissue by T3 via an in vivo effect may be involved in
      a short feedback loop of TSH on TRH release, and [3] ovarian steroid hormones
      play an inhibitory role in regulating T3 effects on the release of TSH and TRH.

PMID- 9551252
TI  - Optimal insemination concentration for human in vitro fertilization (IVF).
AB  - This study is looking for optimal insemination concentration to achieve optimal
      IVF pregnancy. Sperm lateral head displacement, total abnormal form, Kruger
      morphology and index, hypo-osmotic swelling test were significantly correlated
      with fertilization in vitro. Based on those parameters, logistic regression
      models were formulated. These models predict either fertilization probability
      provided with an insemination concentration or insemination concentration
      assigned with a definite fertilization percentage. These models showed that
      increased insemination concentration can increase fertilization percentage. The
      increase of fertilization didn't compensate for the significant loss of
      implantation by increasing insemination concentration.

PMID- 9551253
TI  - Blastocyst formation is a good indicator for attainment of assisted reproduction.
AB  - Blastocyst formation is a late stage of embryogenesis before implantation. The
      examination for the percentage of blastocyst formation (PBF) can predict the
      viability/pregnancy of the assisted reproduction trials. The PBF significantly
      correlates with age and pregnancy. The PBF is significantly lower in the
      intracytoplasmic sperm injection (ICSI) treatment than the conventional IVF
      treatment. The zygotes from immature oocytes give less blastocyst formation than
      the zygotes from mature oocytes. One pronucleus "zygotes" have significantly less
      chance to blastocyst than the normal 2 pronuclei zygotes. A mathematical model is
      proposed, verified, and predicts the hatching/hatched is the rate limiting step
      for the outcome of pregnancy.

PMID- 9551254
TI  - Localization of protein kinase C alpha and zeta during the decidualization in
      pseudopregnant rats.
AB  - Our previous data showed that at least five PKC isoforms (alpha, delta, zeta,
      lambda and tau) were present in the decidualization. In this study, we then
      localized the PKC alpha and zeta by immunohistochemistry in the decidualized
      uterine tissues. The decidualized uterine tissues were induced by trauma
      stimulation and fixed in formalin. The immunofluorescence were photographed by
      confocal microscope. The data revealed that the fluorescence of PKC alpha was
      present in the deciduomata and myometrium. In the deciduomata, PKC alpha was
      mainly located in the surrounding nuclear. This phenomenon of localization was
      especially performed on day 2 and 3 of the decidualization, just on the time of
      higher frequence of cell mitosis. Since the myometrium with hypertrophy did not
      display the phenomenon of perinuclear localization, these suggested that the
      expression and localization of PKC alpha may be associated with the cell
      proliferation. On the other hand, the PKC zeta was also present and distributed
      broadly in the deciduomata and myometrium. This expression was increased and
      similar to the previous Western blot studies. Thus, the data confirmed that the
      various expression and localization of PKC isoforms may be correlated with the
      development of deciduomata.

PMID- 9551255
TI  - [Searching for the ideal cuff].

PMID- 9551256
TI  - [Indications for antireflux surgery of the esophagus].
AB  - In the Western world gastroesophageal reflux disease constitutes the single most
      common benign disorder of the upper gastrointestinal tract. Current medical
      therapy with proton pump inhibitors allows physicians to provide complete symptom
      relief and healing of acute esophageal mucosal injury in practically all affected
      patients. However, up to 50% of patients require maintenance therapy to prevent
      relapse. In these patients laparoscopic antireflux surgery offers an attractive
      and cost-effective alternative to potentially life-long medical therapy.
      Consequently, every patient with persistent or recurrent symptoms and/or
      complications of gastroesophageal reflux who depends on maintenance medical
      therapy to remain in remission is a potential candidate for laparoscopic
      antireflux surgery, particularly if of young age, suffering from side effects of
      medical therapy or worrying about long-term safety of the conservative treatment
      alternatives. A careful selection of patients, objective documentation of
      gastroesophageal reflux disease by 24-h esophageal pH monitoring, and meticulous
      attention to the technical details of the procedure are essential for a
      successful outcome of antireflux surgery.

PMID- 9551257
TI  - [Open antireflux surgery].
AB  - In over 80% of patients with gastroesophageal reflux disease, the Nissen
      antireflux fundoplication gives good long-term results. Dysphagia, inability to
      belch or vomit as well as the gas bloat syndrome are possible sequelae after
      fundoplication. The frequency of these symptoms could be reduced by modification
      of the original Nissen-Rossetti fundoplication into the so-called "floppy" Nissen
      fundoplication, a short and loose wrap of mobilized gastric fundus. Failures of
      the antireflux procedure are mainly due to disruption or displacement of the wrap
      with the telescope phenomenon. Here, reoperation with refashioning of the
      original wrap may lead to same functional results like a primary fundoplication.
      Technical alternatives may selectively be chosen, when gastroesophageal reflux
      disease is complicated by fixated hiatal hernia, esophageal shortening, or
      serious esophageal motility disorders. Such specific anatomic or functional
      abnormalities are detected by preoperative endoscopy, barium swallow, 24-h pH
      monitoring, and manometry. Alternative techniques are mainly transthoracic
      repairs, including the Nissen fundoplication, Collis gastroplasty, and the Belsey
      Mark IV. Modifications of the 360 degrees Nissen operation are partial
      fundoplications like the Hill repair and the Toupet dorsal fundoplication.
      Because of a high failure rate in the long-term follow-up, application of the
      ligamentum teres cardiopexy and of the Angelchik prosthesis is not recommended.

PMID- 9551258
TI  - [Laparoscopic antireflux procedures].
AB  - Laparoscopic antireflux surgery is rapidly replacing traditional operations for
      the treatment of medically refractory gastroesophageal reflux disease. These
      procedures are technically demanding. Troublesome side effects can be minimized
      by carefully selecting patients and using a meticulous and appropriate technique.
      Extensive follow-up data are now emerging and indicate that these procedures can
      offer long-term control of symptoms with few permanent side effects.

PMID- 9551259
TI  - [Endoscopic intraluminal valvuloplasty--a therapy of the future for
      gastroesophageal reflux].
AB  - A new endoscopic intraluminal valvuloplasty is described. The procedure provides
      a simple, easy out-patient approach for antireflux surgery and is applicable to
      patients with early gastroesophageal reflux disease as an alternative to chronic
      life-long medical therapy. The feasibility, durability and efficacy of the
      procedure in baboons are reported.

PMID- 9551260
TI  - [Can "internal intestinal splinting" prevent ileus recurrence? Results of a
      retrospective comparative study].
AB  - The high rate of recurrence after the treatment of adhesive obstruction demands
      special prophylactic treatment. In a 13-year period, 52 out of 95 patients with
      major adhesions were provided with a long nasointestinal tube for intestinal
      splinting intraoperatively. The was being left in situ on an average of 6.6 days.
      After an observation period of at least 36 months a recurrence was seen in 2 of
      these 52 patients (3.9%; causes: volvulus after 6 months/fibrinous peritonitis on
      the 6th postoperative day). Amongst the 43 'non-splinted' patients, recurrence of
      adhesive obstruction was documented in 8 cases (18.6%; causes: adhesions after
      0.3-136.9 months). In the course of after-care abdominal complaints were
      significantly fewer in patients who had been splinted. Complications concerning
      the nasointestinal tubes did not occur. The rate of perioperative complications
      was similar in both groups.

PMID- 9551261
TI  - [Diverticulitis of the cecum and ascending colon].
AB  - Right colon diverticulitis, representing 1-3.6% of cases of diverticular disease
      is an uncommon cause of right lower quadrant pain. Its presentation is difficult
      to distinguish from acute appendicitis. Patients are between 35 and 50 years old,
      have a history of 2-3 days of abdominal pain and few gastrointestinal symptoms.
      The diagnosis is best confirmed by computed tomography and colonoscopy.
      Conservative treatment is justified in uncomplicated disease, whereas
      perforations, abcesses and inflammatory tumors require resection. We describe the
      cases of six patients treated at our institution from 1991 to 1996. Presentation,
      geographic variations, diagnostic procedures and management are discussed.

PMID- 9551262
TI  - [Success and failure in laparoscopic "gastric banding". A report of 3 years
      experience].
AB  - During 3 years, the adjustable gastric band (AGSB) was laparoscopically implanted
      in 224 of 873 patients with morbid obesity. The operation was done by 7 surgeons.
      Problems arising from the operative technique are: early pouch dilatation,
      gastric slippage, gastric perforation, penetration of the band, port infection,
      penetration of the port, defect of the band catheter. These can be avoided by
      care and increasing experience. The late pouch dilatation and the insufficient
      loss of excess weight arise from the unsatisfactory compliance of the patient.
      Critical selection of patients is necessary. Total morbidity in this seria was
      19%, the letality 0.4% and the average excess weight loss within 2 years was 50
      +/- 28%. The results may be improved by restrictive selection of patients and
      great operative routine.

PMID- 9551263
TI  - [Prognostic value of e-cadherin in papillary thyroid carcinoma].
AB  - The prognostic significance of e-cadherin in papillary thyroid carcinoma was
      evaluated in a retrospective study. From September 1985 to December 1996, 113
      patients underwent surgery for papillary thyroid carcinoma. Seventy-eight
      formalin-fixed, paraffin-embedded tissue samples were available for
      immunohistochemical analysis of e-cadherin expression. In 74 of these 78 patients
      the postoperative course is known for 2 months to 35.2 years (median 3.6 years,
      mean: 4.9 +/- 4.8 years). Reduced or negative e-cadherin expression (< or = 20%)
      was associated with advanced T categories of the primary tumours and higher rates
      of synchronous lymph node involvement and distant metastasis. During follow-up in
      this group of patients locoregional tumour recurrence occurred more frequently
      and survival was shorter than in patients with tumours which exhibited e-cadherin
      expression of > 20%. Statistical analysis revealed e-cadherin expression (< or =
      20%/ > 20%), synchronous distant metastasis (M0/pM1, cM1) and radicality of
      resection (R0/R1, 2) as significant risk factors for survival. Our findings
      provide evidence that e-cadherin is a prognostic factor in papillary thyroid
      carcinoma.

PMID- 9551264
TI  - [Guidelines as the principle of rational medical management].

PMID- 9551265
TI  - ["Directions, guidelines, standards"--risk or advantage for physician and
      patient?].

PMID- 9551266
TI  - [Current assessment of physician manpower needs in surgery].

PMID- 9551267
TI  - [Endoscopic surgery. 10 good reasons for integration of flexible endoscopy into
      surgery].

PMID- 9551268
TI  - [Report on the membership meeting of the Regional Westphalia Society of the BDC
      12 November 1997 in Dortmund].

PMID- 9551269
TI  - [Gliding nail osteosynthesis. A new universally applicable implant for management
      of per- and subtrochanteric femoral fractures].
AB  - Age, high physiological load and the great number and different fracture types of
      the proximal femur are the main challenges for implants used in the management of
      these fractures. For use in these types of fracture with immediate restoration of
      full weight-bearing capacity and for reduction of the intra- and postoperative
      complication rate, the gliding nail was developed. The development is based on a
      large number of experimental and clinical examinations of per- and
      subtrochanteric fractures. The advantages of an intramedullary implant and the
      gliding screw systems are combined with increased moment of resistance of the
      double-T femor-neck blade profile. We performed a prospective clinical evaluation
      of the first 186 patients with per- and subtrochanteric fractures who were
      treated between 15 September 1994 and 29 February 1996 in the Aschaffenburg
      Trauma Department with a follow-up examination at least 3 months after the
      operation. The intraoperative complication rate was 1.1%. The postoperative
      complication rate was 4.9%. Change of the blade because of fracture impaction and
      tractus iliotibialis problems was the most frequent problem with 2.2%. The most
      severe complication (1.1%) were caused by subchondral placement of the blade in
      the cranial one-third of the femur head. In these cases reosteosynthesis was
      indicated. Ninety-three percent of the survivors were able to return home. The
      rate of bed-ridden patients (7.7% and 11.7%) was not very different before or
      after the operation. However, many patients do not reach the condition they had
      before the fracture and they are one step worse in mobility and social
      independence.

PMID- 9551270
TI  - [Heparin-associated thrombocytopenia (HAT) type II. An underestimated
      complication in prevention of thromboembolism with heparin].
AB  - We report four patients who developed heparin-associated thrombocytopenia (HAT)
      under heparin prophylaxis. One patient showed no clinical signs, but three had
      severe complications (white-clot syndrome, acute adrenal failure and loss of limb
      because of thromboembolic complication), leading to death in two cases.

PMID- 9551271
TI  - [Salmonella enteritidis infected false aneurysm of the superficial femoral artery
      in an HIV seropositive patient].
AB  - In the course of an infection with human immunodeficiency virus, a large variety
      of complications affecting all organ systems can occur. However, complications
      affecting the vascular system demanding surgical intervention are rare. In the
      case presented we report a 67-year-old HIV-seropositive patient who underwent
      surgery for a huge abscess in the thigh. Intraoperatively unexpectedly we found a
      mycotic aneurysm of the femoral superficial artery and the causactive bacterium
      proved to be Salmonella enteritidis. Because of the rising number of HIV-infected
      patients we suspect that the amount of complications involving the vascular
      system and demanding surgical intervention will also increase. Therefore, when
      diagnosing and deciding on therapy for patients with AIDS, the physician must be
      aware that vascular complications due as a result of HIV infection might occur
      more frequently in the future.

PMID- 9551272
TI  - [Cystic echinococcosis of the spleen].
AB  - Based on the portal infection root, the hydatid disease of the spleen represents
      a rarity. Because of a lack of prospective studies, spleen-preserving procedures
      and splenectomies were published as surgical therapy in case reports. In this
      report, the case of a 72-year-old woman with symptomatic hydatid disease of the
      spleen will be reported. Surgical and pharmaceutical strategy to minimize the
      risk of an OPSI syndrome as well as the value of adjuvant therapy with
      Albendazole will be discussed.

PMID- 9551273
TI  - [Comparison between steam and gas sterilized optics. Costs, availability,
      maintenance].
AB  - METHODS: In a 300-bed acute-care hospital we compared optical instruments
      employed, for orthopedic, urological and gynecological operations during their
      use in practice. The comparison between 33 ethylene oxide(EO)-sterilized optical
      instruments and 14 steam-sterilized optical instruments took into account the
      following criteria: frequency of use; availability; sterilization cycles; kind,
      cost and number of repairs. RESULTS: The 33 EO-sterilized optical instruments
      were handled 1043 times and were repaired 10 times (at a cost of up to 2000 SFR).
      The 14 steam-sterilized optical instruments were treated 1101 times and were
      repaired 8 times (2000 SFR). The total costs were 77,000 SFR for the 14 steam
      sterilized instruments and 132,000 SFR for the 33 EO-sterilized instruments.
      INTERPRETATION: Steam-sterilization is a reasonable, safe and fast method of
      sterilizing optical instruments. We prefer this method, given its advantages
      (less toxicity, personal care and pollution control).

PMID- 9551274
TI  - [Country-wide survey of therapeutic procedures in hemorrhoids and anal fissure].
AB  - A survey among coloproctologists was performed to assess current therapeutic
      concepts for the treatment of hemorrhoidal disease and anal fissure. A total of
      261 clinical and non-clinical proctologists participated, representing the entire
      range of therapies in hospital and practise. A wealth of widely differing, in
      some aspects contradictory concepts were recorded, leaving almost no subject
      entirely undisputed. There are controversies regarding the different therapeutic
      alternatives as well as indications for surgery and choice of operative
      procedure. Future research has to address the existing controversies in order to
      reach a higher degree of standardization in the therapy of these common
      proctological disorders.

PMID- 9551275
TI  - [Postoperative analgesia after endoscopic abdominal operations. Comment on the
      contribution by P. Steffen et al].

PMID- 9551276
TI  - [Surgical wound treatment].

PMID- 9551277
TI  - Health services clinical trials: design, conduct, and cost methodology.
AB  - Randomized clinical trials and their developing methodology have had substantial
      impact on the advancement of medical practice. With the emergence of managed care
      and increased emphasis on the reduction of medical care expenditures, cost
      evaluation is now becoming a part of clinical trial research. The papers by
      Henderson et al. and Manheim that follow address the evolution of health services
      research, its application to multicenter clinical trials in a major U.S. health
      care system, and methods of assessing costs in health services clinical trials.

PMID- 9551278
TI  - Cooperative studies in health services research in the Department of Veterans
      Affairs.
AB  - The Department of Veterans Affairs, through its Cooperative Studies Program, has
      a long history of conducting large-scale, multihospital biomedical clinical
      trials. The agency's Health Services Research and Development Service, although
      newer, has a distinguished record of mainly single-site research into the
      organization, delivery, and financing of health services. In 1990, a joint
      program was initiated to conduct multicenter studies in health services research.
      This article describes the studies developed in the new program and the research
      design issues encountered in planning them. Identification of the patient
      population, specification and measurement of the intervention, and description of
      the control group, as well as attention to the unit of randomization and
      analysis, outcome variables and choice of effect size, data quality, and ethical
      considerations are among the important issues related to the design of these
      studies and future studies in health services.

PMID- 9551279
TI  - Health services research clinical trials: issues in the evaluation of economic
      costs and benefits.
AB  - The costs and benefits of treatment interventions are difficult both to
      conceptualize and to measure. This paper discusses methodologic issues that arise
      in measuring costs, distinguishing between social costs and transfer payments,
      measuring the value of life and limb, and assessing the meaning of cost
      differences. Long-run vs. short-run costs and average vs. marginal costs are
      considered. Sensitivity analysis to assess the robustness of results to
      alternative assumptions is stressed. Cost-benefit and cost-effectiveness analyses
      are seen as important in assessing the policy implications of clinical trials; a
      proper cost-benefit analysis allows the reader to understand how results relate
      to the assumptions made in the analyses.

PMID- 9551280
TI  - Do certain countries produce only positive results? A systematic review of
      controlled trials.
AB  - OBJECTIVE: To determine whether clinical trials originating in certain countries
      always have positive results. DATA SOURCES: Abstracts of trials from Medline
      (January 1966-June 1995). STUDY SELECTION: Two separate studies were conducted.
      The first included trials in which the clinical outcome of a group of subjects
      receiving acupuncture was compared to that of a group receiving placebo, no
      treatment, or a nonacupuncture intervention. In the second study, randomized or
      controlled trials of interventions other than acupuncture that were published in
      China, Japan, Russia/USSR, or Taiwan were compared to those published in England.
      DATA EXTRACTION: Blinded reviewers determined inclusion and outcome and
      separately classified each trial by country of origin. DATA SYNTHESIS: In the
      study of acupuncture trials, 252 of 1085 abstracts met the inclusion criteria.
      Research conducted in certain countries was uniformly favorable to acupuncture;
      all trials originating in China, Japan, Hong Kong, and Taiwan were positive, as
      were 10 out of 11 of those published in Russia/USSR. In studies that examined
      interventions other than acupuncture, 405 of 1100 abstracts met the inclusion
      criteria. Of trials published in England, 75% gave the test treatment as superior
      to control. The results for China, Japan, Russia/USSR, and Taiwan were 99%, 89%,
      97%, and 95%, respectively. No trial published in China or Russia/USSR found a
      test treatment to be ineffective. CONCLUSIONS: Some countries publish unusually
      high proportions of positive results. Publication bias is a possible explanation.
      Researchers undertaking systematic reviews should consider carefully how to
      manage data from these countries.

PMID- 9551281
TI  - Laboratory data in clinical trials: a statistician's perspective.
AB  - Even though laboratory data provide the best indicators for systemic toxicities
      in clinical trials of investigational medications, many applied statisticians
      lack a basic understanding of the interpretation of such data. Understanding is
      essential to a statistician's ability to help evaluate a patient's overall safety
      experience in a trial, the latter being the primary objective for collecting
      laboratory data in the trial. In this paper, we discuss the purpose of conducting
      laboratory evaluations as well as some hidden issues concerning the current
      practice of laboratory data analysis. The issues include the use of reference
      ranges, the one-parameter-at-a-time approach, and the exploratory nature of
      safety data analyses.

PMID- 9551282
TI  - Threats to the validity of clinical trials employing enrichment strategies for
      sample selection.
AB  - Subject selection and exclusion criteria employed in typical clinical
      effectiveness trials of investigational new drugs have two fundamental aims: (1)
      to ensure that patients entering a study are truly suffering from the condition
      the drug is intended to treat and (2) to maximize the likelihood that the study
      will detect an effect of the drug if, in fact, one exists. Typical protocol
      selection criteria not only specify exacting procedures for establishing and
      documenting the diagnosis of those recruited for a study but also seek to
      increase, relative to the prevalence in the general population, the proportion of
      individuals in the sample likely to respond to pharmacological treatment. Because
      it is ordinarily impossible to learn prior to extensive clinical experience with
      a new drug which, if any, patient characteristics reliably predict a consistent
      treatment response, strategies for sample "enrichment" typically operate by
      excluding patients (for example, those with very advanced and/or complicated
      illness, those with serious concomitant illness, those at the extremes of age,
      those with very mild illness, and so forth) in whom a dependable response to
      treatment seems unlikely on logical and/or generic grounds. Some studies use
      positive strategies for sample "enrichment." In studies evaluating drugs intended
      to treat recurrent episodes of psychiatric illnesses, many protocols recommend
      selective recruitment of patients with a history of meaningful positive responses
      to antipsychotic treatment during prior episodes. Sample selection procedures of
      these kinds impose limits on the generalizability of a study's results (i.e.,
      external validity), but the use of nonrandom patient samples is ordinarily held
      to have no effect on the internal validity of the results. In short, studies
      employing highly selected patient samples are, despite their limited external
      validity, regularly accepted as valid sources of evidence bearing on a drug's
      effectiveness. There are exceptions, however; this paper describes one in which
      the use of a seemingly innocuous sample enrichment maneuver proved highly
      damaging to the ultimate credibility of an important multicenter trial. In
      particular, exposure to an experimental treatment during an open qualification
      phase may invalidate drug-placebo comparisons made during a later randomized,
      blinded, controlled phase. Our review of the trial also reveals that the
      enrichment maneuver employed probably failed to accomplish its intended aims,
      selecting patients whose improvements on the outcome variable may be as
      reasonably ascribed to chance as to drug effect. This is all the more surprising
      because the method of sample enrichment employed has much in common with those
      long recommended in the clinical trial literature.

PMID- 9551283
TI  - Comparative evaluation of two models for estimating sample sizes for tests on
      trends across repeated measurements.
AB  - Two equations for calculating sample sizes that are required for power in testing
      differences in rates of change in repeated measurement designs have been
      presented by different authors. One equation provides support for the conclusion
      that increased frequency of measurements across a treatment period of fixed
      duration enhances power of the tests. The other equation supports the
      counterintuitive conclusion that increased frequency of measurements actually
      tends to decrease power in the presence of realistic serial dependencies in the
      data. Monte Carlo methods confirm that the equation providing support for the
      latter conclusion is accurate, whereas the alternative equation tends to
      underestimate sample sizes required for power in testing differences in slopes of
      regression lines fitted to changes in the repeated measurements across time when
      symmetry is absent from the covariance structure.

PMID- 9551284
TI  - The cost-benefit of a randomized trial to a health care organization.
AB  - Clinicians and patients make many decisions in situations where optimal treatment
      is uncertain. Despite well-published advantages of clinical trials for reducing
      such uncertainties, a trial may not be conducted because the sample size
      indicated by classical, hypothesis-testing methods is so large that no one
      institution could afford to sponsor the trial. By explicitly taking into
      consideration the costs and benefits of a trial, Bayesian statistical methods
      permit estimation of the value to a health care organization conducting a
      randomized trial instead of continuing to treat patients in the absence of more
      information. This paper describes a method for calculating the cost-benefit to a
      health care organization conducting a clinical trial, and the expected sample
      size to adequately resolve the uncertainties about which treatment is better. The
      method is illustrated in the case of a proposed clinical trial of a drug to
      prevent multiorgan system failure and death in patients admitted to the Stanford
      University surgical intensive care unit. This method should permit health care
      organizations to evaluate a proposed trial's expected cost-benefit and the
      expected sample size that will resolve the question of interest, and thereby
      assist in the process of deciding whether to conduct the trial.

PMID- 9551286
TI  - Neurometabolic disease.
AB  - Advances in knowledge of neurometabolic disease continues. Of great interest to
      the neurologist are the definitions of the molecular defects in Niemann-Pick C
      disease, Refsum disease, and five of the disorders of peroxisome biogenesis,
      including rhizomelic chondrodysplasia punctata. Duplication of the proteolipid
      protein gene is the most common molecular abnormality in Pelizaeus Merzbacher
      disease. Therapies for guanidinoacetate methyltransferase deficiency and for 3
      phosphoglycerated dehydrogenase deficiency appear promising. Animal models have
      been developed for X-linked adrenoleukodystrophy, metachromatic leukodystrophy
      and Zellweger syndrome and will aid in the understanding of pathogenesis and the
      evaluation of therapy.

PMID- 9551285
TI  - TRIPOD (TRoglitazone In the Prevention Of Diabetes): a randomized, placebo
      controlled trial of troglitazone in women with prior gestational diabetes
      mellitus.
AB  - The TRoglitazone In the Prevention Of Diabetes (TRIPOD) trial is a single-center,
      randomized, placebo-controlled, double-masked study. The primary aim of the
      TRIPOD trial is to test the hypothesis that chronic administration of
      troglitazone to nondiabetic women with prior gestational diabetes mellitus (GDM)
      will improve whole-body insulin sensitivity and reduce the incidence of non
      insulin-dependent diabetes (NIDDM). Because troglitazone is already known to
      lower blood glucose concentrations in persons who have developed NIDDM, an
      additional aim of the project will be to determine whether early intervention
      with troglitazone will achieve better final glycemic control than can be achieved
      by later intervention. In addition, since troglitazone treatment is expected to
      improve insulin sensitivity and may prevent or delay a decline in glucose
      tolerance, we also plan to determine whether long-term troglitazone treatment
      alters the development or progression of atherosclerosis. In this article we
      describe the experiment's design, the study's endpoints and methods for
      determining those endpoints, methods for assessing quality of life, and proposed
      methods for statistical analyses. The unique two-phase study design of the TRIPOD
      trial will permit testing not only of the biological question about reversal of
      insulin resistance and prevention of diabetes, but also of the clinical question
      about whether early intervention is superior to late intervention. Results from
      this trial will have an important impact on the monitoring and treatment of
      patients at high risk for NIDDM.

PMID- 9551287
TI  - Prevention of neural tube defects: vitamins, enzymes and genes.
AB  - Neural tube defects can be prevented by folic acid, although the mechanism of
      this action is unclear. Studies of a series of folate-related enzymes have so far
      failed to pin-point the nature of the metabolic defect in the neurulation-stage
      embryo that is corrected by folic acid. Approximately 30% of neural tube defects
      appear resistant to folic acid and recent work in a mouse genetic model system
      suggests that administration of myo-inositol may be a complementary therapeutic
      option. The large number of mouse genes known to cause neural tube defects
      provide a starting point for identifying the genetic basis of the human defects.

PMID- 9551288
TI  - Craniofacial developmental abnormalities.
AB  - Major advances have been made in the elucidation of the molecular basis of a
      number of human dysmorphic syndromes involving abnormalities of craniofacial
      development. This will lead, in turn, to a greater understanding of the
      mechanisms that underlie normal craniofacial development.

PMID- 9551289
TI  - Neuropsychiatric disorders.
AB  - Neuropsychiatric disorders of childhood include autism spectrum disorders,
      disorders comprising attention deficits (attention-deficit-hyperactivity disorder
      and deficits in attention, motor control and perception), tics (motor or vocal,
      or both), and obsessions and compulsions (obsessive-compulsive disorder). They
      affect a small proportion of the child population. They can now reliably be
      diagnosed, and are valid and clinically meaningful conditions. Effective
      interventions are available for most of these disorders.

PMID- 9551290
TI  - Developmental perspectives on epilepsy.
AB  - This paper reviews current knowledge about epileptogenesis in the developing
      brain. Animal studies indicate that the maturational balance of excitatory and
      inhibitory neurotransmitter systems should result in an increased susceptibility
      to seizures. However, the reason for specific age-locked syndromes and the high
      rate of impairments secondary to early onset epilepsy remain mysterious. Present
      research activity is directed to prevention and amelioration of these severe
      cognitive and psychiatric impairments.

PMID- 9551291
TI  - Integration of structural and functional data.

PMID- 9551292
TI  - Mechanisms and experimental models of seizure generation.
AB  - Over the past year evidence has accumulated against the idea that seizures
      require re-entrant activity between spatially separate structures. Seizures in
      vivo typically do involve interconnected, spatially separate brain regions, but
      they often show no net phase lag around the putative circuit. In many cases
      seizure-like events can arise from localized regions such as the entorhinal
      cortex or hippocampus proper, through mechanisms that are starting to be
      identified.

PMID- 9551293
TI  - Febrile seizures: genetics and relationship to other epilepsy syndromes.
AB  - The relationship between febrile seizures and epilepsy has long been debated. We
      argue that there is some specificity to the types of epilepsy that follow febrile
      seizures, rather than febrile seizures being a nonspecific marker of a lowered
      seizure threshold. The relationship between febrile seizures and later epilepsy
      is frequently genetic. Recent clinical and molecular genetic studies suggest that
      there are a number of syndrome-specific genes for febrile seizures.

PMID- 9551294
TI  - Differential diagnosis of sleep disorders, non-epileptic attacks and epileptic
      seizures.
AB  - Making a correct diagnosis in patients presenting with attack disorders is
      important. The clinical features of autosomal dominant nocturnal frontal lobe
      epilepsy and concussive seizures are reviewed. Recent work on the diagnosis and
      investigation of psychogenic non-epileptic attacks, drop attacks, falls, syncope
      and sleep disorders is discussed.

PMID- 9551295
TI  - New drugs for epilepsy.
AB  - Seizure freedom with no side-effects is the aim of treatment, and new
      antiepileptic drugs have not lived up to expectations; only a few patients with
      chronic epilepsy have been rendered seizure-free. These treatments have side
      effects but their safety profile may be better than older alternatives, although
      chronic effects have not yet been established. This article reviews newly
      marketed antiepileptic drugs. It concentrates on shortcomings of current
      antiepileptic treatment and on the way drugs are developed. A new approach to
      treatment is long overdue. The development of rational antiepileptic treatments
      should be strongly encouraged. More clinically relevant paradigms need to be
      developed and incorporated into clinical trial programmes as these are presently
      biased in their designs towards regulatory issues.

PMID- 9551296
TI  - The epidemiology and management of status epilepticus.
AB  - Status epilepticus refers to a prolonged seizure state, usually taken as lasting
      30 min or longer. This review considers recent studies of the epidemiology of
      status epilepticus; these have confirmed the high incidence and the high
      associated mortality and morbidity. Advances in the management of status
      epilepticus are also reviewed but despite these advances there is still a lack of
      good comparative studies on which to base treatment regimens.

PMID- 9551297
TI  - The current state of epilepsy surgery.
AB  - Epilepsy surgery is an effective therapy for many patients with refractory
      partial seizures. The results of epilepsy surgery have improved with advances in
      the evaluation of patients for surgery and the care of patients during and after
      surgery. This review looks at recent innovations in imaging modalities to
      identify the candidates for surgery who will benefit most, to identify subtle
      pathology, to resect the epileptogenic focus more precisely, and to preserve
      functionally important cortex in order to achieve the best possible outcome.
      Patient selection and the identification and removal of the epileptogenic focus,
      in a safe manner, are crucial for good outcome.

PMID- 9551298
TI  - Developmental disorders.

PMID- 9551299
TI  - Seizure disorders.

PMID- 9551301
TI  - The prevention of neural tube defects.
AB  - The prevention of neural tube defects is a complex problem. The genetic
      associations may ultimately allow the prepregnancy identification of women at
      high risk of a neural tube defect. Education of both the public and healthcare
      providers has been shown to increase awareness, but the majority of women do not
      take folic acid before and in the early part of pregnancy. Food fortification
      will be effective in increasing the folate levels of the population and will have
      a benefit even at low doses of fortification.

PMID- 9551302
TI  - Antenatal screening for aneuploidy.
AB  - There are several methods of antenatal screening for aneuploidy. Most are aimed
      at the identification of women at increased risk of Down syndrome, the most
      common abnormal karyotype conferring a significant risk of serious long-term
      morbidity. Traditional maternal-age-based screening has largely been replaced by
      programmes based on biochemical markers in maternal serum in the second trimester
      of pregnancy. However, in recent years there has been a considerable drive
      towards earlier screening such that there are now a range of potential programmes
      based on various combinations of maternal age, serum markers and ultrasound
      findings. There is currently much debate as to which are the most effective
      methods of screening for aneuploidy.

PMID- 9551303
TI  - Applied molecular genetic techniques for prenatal diagnosis.
AB  - Molecular laboratory techniques are increasingly important in the evaluation of
      fetuses at risk for a single gene disorder or chromosomal abnormality and for the
      detection of genetic or other conditions that can lead to an adverse fetal or
      maternal outcome. The localization and identification of novel disease genes
      allows for mutation analysis or linkage studies on fetuses at risk for these
      disorders. New assays or techniques for mutation detection in single gene
      disorders such as amplification refractory mutation system polymerase chain
      reaction, fluorescent polymerase chain reaction, heteroduplex analysis and the
      protein truncation test are now applied in prenatal diagnosis. Recent advances in
      molecular cytogenetics, such as comparative genomic hybridization, the primed in
      situ labeling technique, the development of new telomeric probes and spectral
      karyotyping, are being evaluated for their role in the prenatal diagnosis of
      chromosomal abnormalities. These methods may greatly improve the accuracy and
      applicability of preimplantation genetic diagnosis or diagnosis on fetal cells
      isolated from maternal blood.

PMID- 9551305
TI  - Novel fetal imaging techniques.
AB  - Fetal imaging technology is evolving rapidly, and new techniques are being
      evaluated to establish their role in the assessment of the fetus. It is essential
      that these methods of fetal imaging are carefully assessed to ascertain if they
      provide additional information to assist in the clarification or understanding of
      fetal disease states that is not already provided by current conventional imaging
      techniques.

PMID- 9551304
TI  - Stem cell transplantation into the fetal recipient: challenges and prospects.
AB  - The interest in therapeutic intervention for those inherited disorders that can
      be diagnosed early in pregnancy has recently intensified. In-utero
      transplantation of haematopoietic stem cells (IUT-HSC), a therapy which could be
      proffered before pathological manifestations of a disorder become apparent,
      offers considerable potential benefit. However, as reports of IUT-HSC procedures
      become more prolific, it is necessary to consider the optimum modus operandi for
      each group of disorders targeted for therapy in order to develop effective
      procedures that make a real difference to the outcome. This review outlines the
      current status and prospects of IUT-HSC. It also offers a view of some of the
      challenges for IUT-HSC to overcome to find wider clinical applications.

PMID- 9551306
TI  - Fetal thrombocytopenia.
AB  - In idiopathic thrombocytopenic purpura, the low risk of fetal bleeding in the
      perinatal period does not justify routine cordocentesis. Platelet counts of
      second newborns correlates well with that of their siblings. In neonatal
      alloimmune thrombocytopenia, the initial platelet count at cordocentesis in the
      second trimester is low in the next pregnancy. Weekly high doses of intravenous
      gammaglobulin to the mother results in a rise of fetal platelet count in
      approximately 70% of cases and may protect the fetus against intracranial
      haemorrhage in cases without significant platelet rise. With the exception of
      cases with a prior infant with spontaneous fetal intracranial haemorrhage, the
      use of diagnostic fetal blood sampling to confirm neonatal alloimmune
      thrombocytopenia is controversial.

PMID- 9551307
TI  - Vertical transmission of viral infections.
AB  - A variety of congenital viral infections are responsible for a large proportion
      of the mortality and morbidity in infancy and childhood. Vertical transmission
      may occur during primary maternal infection or during chronic or recurrent
      infection, with different implications for counselling and testing in pregnancy.
      Strategies for the diagnosis and prevention of mother-to-child transmission
      differ according to the timing and mechanisms involved. As demonstrated by
      hepatitis B research in the past and human immunodeficiency virus today,
      multicenter cohort studies and clinical trials are a key to developing effective
      interventions.

PMID- 9551308
TI  - Pre-eclampsia--still a disease of theories?
AB  - The pathophysiology of pre-eclampsia remains poorly understood. Moreover, there
      is no reliable predictive test and no effective prophylactic therapy for this
      disease. Advances have, however, recently been made in our understanding of the
      genetics of pre-eclampsia and in the processes which lead to abnormal
      trophoblastic invasion in pre-eclampsia. Prediction and prevention are intimately
      linked, and both problems will only be solved by further unravelling of the
      complex pathophysiology of pre-eclampsia.

PMID- 9551309
TI  - Inherited thrombophilia and pregnancy.
AB  - Inherited thrombophilia is associated with an increased risk of thrombosis.
      Classically it consists of protein C and protein S deficiency, activated protein
      C resistance and antithrombin III deficiency. In pregnancy, in addition to
      thrombosis, inherited thrombophilia is associated with poor obstetric outcome,
      including recurrent miscarriage, late fetal loss, abruption and pre-eclampsia.
      Hyperhomocysteinaemia is a newly recognized cause of familial thrombophilia. It
      is likely that further causes such as prothrombin gene mutations will be added to
      the rapidly expanding list. The diagnosis of some forms of genetic thrombophilia
      must, however, be approached with caution during pregnancy, particularly protein
      S deficiency and activated protein C resistance.

PMID- 9551310
TI  - Consequences of fetal growth restriction.
AB  - An increasing number of diseases in child and adult life are now thought to have
      their origins in the fetal period. Central to this predisposition is restriction
      of fetal growth. During the period reviewed in this article, the associations
      between adult hypertension and low birthweight were confirmed, and numerous
      studies have investigated possible mechanisms by which the metabolism of an
      individual may be programmed by an adverse intrauterine environment. The
      consequences in adult life of intrauterine undernutrition now highlight prenatal
      care as one of the most crucial issues in medicine and challenge many aspects of
      current obstetric decision-making. Research targeting fetal growth and
      development can be expected to result in improved health at all ages.

PMID- 9551312
TI  - Prenatal diagnosis.

PMID- 9551311
TI  - Preterm labour: recent advances in understanding of pathophysiology, diagnosis
      and management.
AB  - Recent advances in the importance of sociodemographic factors, including maternal
      stress, as well as potential predictors of preterm birth are reviewed. The
      recommended role of adjunctive antibiotic therapy, in women with preterm
      premature rupture of the membranes but not in women with intact membranes, is
      discussed. The possibility of causes other than those related to infection in
      preterm rupture of the membranes is raised, and new information regarding the use
      of glucocorticoids and tocolytics is presented. Despite steady improvements in
      neonatal survival and morbidity rates over the past decade primarily as a result
      of improved neonatal care, there has been no corresponding decrease in the
      incidence of preterm birth. An improved understanding of the pathophysiology and
      diagnosis of preterm birth remains one of the greatest challenges in obstetric
      care in this decade.

PMID- 9551313
TI  - Maternal-fetal medicine.

PMID- 9551314
TI  - Coarctation of the aorta: an update.

PMID- 9551315
TI  - [Enhancer of the scute gene can activate a promoter found at another locus].

PMID- 9551316
TI  - [Possible participation of secondary biogenic radiation in appearance of an
      "adaptive response"].

PMID- 9551317
TI  - [Effect of certain opiates on the stability of an artificial lipid bilayer
      membrane].

PMID- 9551318
TI  - [Effect of helium-neon laser radiation on growth and development of newborn
      rats].

PMID- 9551319
TI  - [Paradoxical sleep--an indicator of various forms of hypometabolism in mammals
      and birds].

PMID- 9551320
TI  - [Myelopeptide-4--a new endogenous factor for differentiation of myeloid cells].

PMID- 9551322
TI  - [Development of organs of hearing and balance in representatives of eared seals
      (Eumetopias jubatus)].

PMID- 9551321
TI  - [Seasonal dynamics of abdominal gland function and marking activity in Mongolian
      (Meriones unguiculatus), midday (M. meridianus), and Tamarisk (M. tamariscinus)
      gerbils].

PMID- 9551323
TI  - [Protein products of zeste, e(y)1 and e(y)3 genes can effect the insulation
      process].

PMID- 9551324
TI  - [Electrocatalytic oxidation of substrates by immobilized Gluconobacter oxydans
      cells in the presence of an electron transport mediator].

PMID- 9551325
TI  - [Distance between homologous regions before pairing and probability of crossing
      over in them].

PMID- 9551326
TI  - [Dynamics of the contractile activity of murine uterus during pregnancy].

PMID- 9551327
TI  - [Experimental study of the kinematics of the dolphin tail fin].

PMID- 9551328
TI  - [Botulinum toxin A in dermatology].
AB  - Based on its unique botulinum toxin is referred to as the most poisonous poison.
      Its specific inhibition of the acetyl-cholin-dependent neuromuscular transmission
      is used by ophthalmologists and neurologists for the relaxation of spastic or
      dystonic muscles, preferably in muscle groups in the head and neck area.
      Analogously, it is being used by dermatologists to remove facial wrinkles by
      paralyzing mimic muscles which account for mechanically induced wrinkling. Apart
      from this purely cosmetic use, botulinum toxin has gained recent attention in
      dermatology as a potent treatment modality for circumscribed hyperhidrosis.

PMID- 9551329
TI  - [p16(INK4A)/CDKN2--the "melanoma gene"? Status of research and outlook].
AB  - The gene of the cyclin-dependent kinase 4 (CDK4)-inhibitor p16INK4A (CDKN2/MTS1)
      has been proposed as a candidate for a tumor-suppressor gene located on
      chromosome 9p21, a frequently deleted region in a series of human cancers
      including malignant melanoma. An increasing and sometimes conflicting body of
      data has accumulated regarding the frequency of homozygous deletions and
      mutations as well as the importance of p16INK4A in malignant melanoma. The
      purpose of this review is therefore to summarize the current knowledge on
      p16INK4A and to discuss its biologic significance in the pathogenesis of
      melanocytic tumors.

PMID- 9551330
TI  - [Axillary hyperhidrosis: successful treatment with botulinum toxin A].
AB  - Severe hyperhidrosis may present as a vexing condition for the patient and a
      therapeutic challenge for the physician. As botulinum toxin-A (BT-A) can potently
      block cholinergic sympathic innervation of sweat glands it was used in an open
      trial for controlling severe axillary hyperhidrosis. After visualization of
      hyperhidrosis using the iodine-starch-test BT-A (Dysport, 400 Units) was injected
      intradermally in one axilla. One week later gravimetric quantification of sweat
      secretion revealed a reduction of sweating to 4-9% of initial values. In order to
      rule out daily variations as well as other factors interfering with sweat
      production BT-A treatment was restricted to only one axilla in each individual
      clearly demonstrating extensive anhidrotic efficacy on the treated side only. The
      treatment was well tolerated without side-effects and was assessed as 'completely
      satisfying' by all patients. BT-A may offer a fast, safe and highly effective
      therapeutic option for severe hyperhidrosis.

PMID- 9551331
TI  - [Desmoplastic squamous epithelial carcinoma of the skin and lower lip. A
      morphologic entity with great risk of metastasis and recurrence].
AB  - The desmoplastic type of the squamous cell carcinoma (DSCC) of the skin is an
      entity which is readily distinguished by light microscopy. The DSCC has fine
      branches surrounded by a desmoplastic stroma and shows in some cases typical
      perineural, perivascular and widespread intradermal invasion (maximum 6 cm!).
      This type accounts for 8.2% (n = 44) of our collective of 594 squamous cell
      carcinomas (SCC) of the skin and vermilion border. Clinically DSCC look like
      other malignant epithelial tumors of the skin. All tumors were followed up for at
      least 3 years (maximum 10 years). The local recurrence rate was high (24.3%) even
      though micrographic surgery was carried out. The rate of local or regional
      metastasis was also very high (22.7%). In comparison the recurrence rate and the
      rate of metastasis of the remaining common 91.8% SCC's (n = 550) was low: 2.6%
      and 3.8%, respectively. The DSCC seems to be identical with the so called
      neurotropic SCC, the fine stranded SCC or the SCC with perineural invasion which
      have a high rate of local recurrence and metastasis as well, but DSCC is a better
      generic histopathologic term for the entire group. The DSCC is best treated with
      micrographic surgery and wider safety margins than any other type and should be
      followed up very frequently.

PMID- 9551332
TI  - [Therapy of hyperhidrosis with tap water iontophoresis. Positive effect on
      healing time and lack of recurrence in hand-foot eczema].
AB  - Hyperhidrosis is due to an overfunction of eccrine glands (triggered by the
      autonomous nervous system) and may be a cofactor for palmoplantar eczema
      (dermatitis). Tapwater iontophoresis was used in 54 patients with hyperhidrosis
      manuum et pedum. After 10 applications directed by the dermatologist, 89% of
      patients noted an improvement in their hyperhidrosis. 20 patients suffering from
      palmoplantar eczema (dermatitis) who continued the treatment at home for at least
      6 months were compared with a historical sex- and age-matched group of 20 eczema
      patients without iontophoresis: The factors evaluated were the time needed for
      clearing and the relapse-free interval. Though iontophoresis-treated patients had
      a slightly faster clearing, this was statistically not significant (20 vs. 22.3
      days; p > 0.05). However, the difference for relapse-free interval between the
      two groups was statistically highly significant (24.8 weeks vs. 8.35 weeks; p <
      0.0001). Tapwater iontophoresis seems to be effective not only to control
      sweating. According to recently published data, galvanization seems to have a
      capsaicin-like effect as well. Our hypothesis is therefore, that galvanization
      with tapwater iontophoresis interrupts the neurogenic inflammation and prolongs
      the relapse-free interval in hyperhidrotic palmoplantar eczema (dermatitis).

PMID- 9551333
TI  - [Hereditary angioedema in the German-speaking region].
AB  - A multicentre, retrospective study of hereditary deficiency of C1-esterase
      inhibitor (C1-INH) function, a deficiency which clinically manifests as
      hereditary angioedema (HAE), was performed in six centres in Germany, Austria and
      Switzerland. 242 individuals were registered with proven functional or
      quantitative deficiency of C1-INH who belonged to kindered with disease
      manifestation in 2 to 6 generations. Considering the total population in the
      three countries and the number of registered individuals, a frequency of the
      deficiency of 0.02 x 10(-4) was calculated. As this epidemiological study
      involved only 6 centres, a 10 to 100 times higher frequency of C1-INH deficiency
      is estimated to be a more realistic value. Out of the 242 registered individuals
      110 were evaluated for type and location of clinical manifestation of the
      deficiency, the laboratory data and the therapy outcome. 86 (78.2%) of the
      patients belonged to the "common type" and 24 (21.8%) to the "variant type" of
      HAE. In 53.9% of the cases first manifestation of the disease was before the age
      of 20 years. In only 3.9% of the patient population did the disease begin after
      40 years of age. A mean time lag of 5,3 years was observed, between the first
      manifestation and correct diagnosis. Initial diagnosis was correct in only 31.8%
      of the cases of which dermatologists provided 51.7%. False diagnoses include
      urticaria (41.3%), allergy (20%), acute abdomen (18.7%), angina (8%), rheumatoid
      disease (5.3%) and intracranial haemorrhage, CNS tumour, epilepsy, migraine
      (5.3%). The distribution pattern of HAE resembled that of intolerance reactions
      and pseudoallergies. Urticarial lesions were not associated with C1-INH
      deficiency. 24% of the patients had at least one episode of laryngeal edema. 40%
      of patients were unable to identify a trigger of edema formation. The others
      indicated as triggers trauma, hormonal changes, mental stress, insect stings and
      in a few cases food and drugs. Menstruation and oral contraceptives aggravated or
      made disease manifestations more frequent. In contrast, during pregnancy in many
      cases clinical manifestations improved and delivery posed no problems. The
      possibility of HAO is very much suggested by the tailure of edema to respond to
      classical anti-allergic therapy. Therapy of choice of acute attacks is C1-INH
      concentrate. No side reactions, antibody formation or virus transmission have
      been observed. For long term prophylaxis danazol, an attenuated androgen, or
      tranexamic acid, a protease inhibitor, was chosen. The daily dose of danazol
      should be kept as low as possible because of its anabolic, anti-estrogenic, anti
      gestagenic, and anti-gonadotropic effects. Indeed, adverse reactions were
      observed in 41.7% of patients receiving danazol. Frequencies of adverse reactions
      were twice as common in women as in men. Adverse reactions were dose dependent
      and reversible except for one woman with irreversible deepening of her voice.
      Measuring C1r is a effective way to assess C1-INH function and monitor therapy.

PMID- 9551334
TI  - [Dose-dependent pellagroid skin reaction caused by carbamazepine].
AB  - A 11-year-old girl suffering from grand mal epilepsy underwent antiepileptic
      therapy with carbamazepine (600 mg/daily). Two weeks after increasing the dose
      (900 mg/day) she suddenly developed relatively sharply limited, sunburn-like
      brown reddish macular lesions with central scaling and partly hyperkeratotic
      areas on the hands, feet, face, knees, gluteal and axillar regions. Otherwise no
      health disorders were found; in particular no neurological or gastrointestinal
      symptoms occurred. After reduction of the doses (450 mg/day) these skin lesions
      faded away. With exception of elevated serum levels of carbamazepine,
      nicotinamide and vitamin B6, all blood tests were in normal range. Interactions
      of carbamazepine with the vitamin B6- nicotinamide metabolism are the reason for
      these previously undescribed cutaneous side effects in connection with
      carbamazepine therapy. The present case demonstrates a toxic, non-allergic
      reaction during carbamazepine treatment with pellagroid skin symptoms.

PMID- 9551335
TI  - [Allopurinol as an inducer of acute graft-versus-host-like drug reaction. Case
      report with review of the literature].
AB  - Although drug eruptions resembling graft-versus-host disease are rare, GvH-like
      reactions to the sulfhydryl group of drugs (penicillamine, captopril, gold
      sodium), phenobarbital and hepatitis vaccine have been described. Clinical
      reports concerning acute GvH-like drug rash are very uncommon and restricted to
      acetylsalicylic acid and spironolactone. We report on a patient who developed an
      acute GvH-like drug reaction caused by allopurinol. To our knowledge this variant
      of cytotoxic drug eruption has not yet been reported in literature.

PMID- 9551336
TI  - [Annular erythema in childhood--a new eosinophilic dermatosis].
AB  - Annular erythema of infancy is a rare and little-known entity. Since its initial
      description by Peterson and Jarratt in 1981 only 4 further cases have been
      reported. We present the first case in the German literature. A 4-year-old boy
      developed non-itching erythematous papules on the trunk which evolved into
      annular and gyrate erythemas within weeks. The condition showed a relapsing
      course with disease-free intervals of several months duration. There were no
      general complaints. Laboratory investigations including detailed serological
      tests for infectious diseases were normal. Histopathology showed a striking
      eosinophilic inflammatory infiltrate predominantly in perivascular areas, without
      peripheral blood eosinophilia. The clinical differential diagnosis of annular
      erythema of infancy includes erythema annulare centrifugum, while microscopically
      one must exclude eosinophilic cellulitis (Wells' syndrome). The etiology is
      unknown and there is no effective therapy. In our case, as well as in all
      previously published cases, the disease resolved spontaneously. Therefore, it may
      be considered benign and self-limited.

PMID- 9551337
TI  - [Zosteriform lichen aureus].
AB  - Lichen aureus is a special localized variant of purpura pigmentosa chronica. A
      patient presented with an unusual striate and segmental or zosteriform
      distribution of lichen aureus involving the left leg and lower abdominal area.
      Histology showed the characteristic dense band-like infiltrate consisting mainly
      of small lymphocytes and numerous hemosiderin-containing macrophages. No
      underlying infection or medication could be identified as a trigger. The lesions
      did not respond well to topical corticosteroid therapy.

PMID- 9551338
TI  - [History of the Krefeld Dermatology Clinic].
AB  - The dermatology clinic in Krefeld has treated a wide range of patients since its
      founding in 1845. Nowadays the spectrum consists of allergology, occupational
      dermatology, phototherapy, dermatosurgery, phlebology and proctology as well as
      special clinics for andrology, sexually transmitted diseases and patients with
      HIV-infection.

PMID- 9551339
TI  - [HiVision video technique in international presentations--close to the skin even
      in the last row of the auditorium].

PMID- 9551340
TI  - [Thoughts of a (relatively) unknown beauty].

PMID- 9551341
TI  - [Otto Braun-Falco Alumni Lecture, Heidelberg, 5 April 1997. Meeting report].

PMID- 9551342
TI  - [Report on the 1st International "Molecular Andrology" Workshop in
      Rauischholzhausen Castle, 5-6 May 1997].

PMID- 9551343
TI  - [3rd International Conference on Varicella Zoster Virus (VZV) 9 to 11 March 1997,
      Palm Beach, Florida, USA. Meeting report].

PMID- 9551344
TI  - [Skin diseases and genetic instability. II. Genetic dermatoses with genetic
      instability].

PMID- 9551346
TI  - [Antibiotics and atherosclerosis].

PMID- 9551345
TI  - [Skin-derived antimicrobial peptides. Interview with Prof. Dr. Jens Schroder,
      Kiel University Dermatologic clinic. Interview by D. Petzoldt, J. Krutmann].

PMID- 9551347
TI  - [Deep venous thrombosis and severe burns].
AB  - Deep venous thrombosis (DVT) is a frequent and potentially serious complication
      in severely burned patients. We report the case of a burned patient (40% of total
      body surface burned), who had right femoral deep venous thrombosis and severe
      pulmonary embolism, although a prophylaxis was conducted with low molecular
      weight heparin, graduated compression stockings and rotating bed. This case shows
      that DVT early diagnosis and prophylaxis is difficult in severely burned
      patients. Systematic screening of DVT by duplex scan is possible only for femoral
      veins, which renders duplex scan more suitable for femoral catheter follow up
      than for systematic DVT screening. Computed tomography venography seems to be a
      valuable tool in the diagnosis of proximal thrombosis. Prophylaxis is best
      achieved with the use of preventive low molecular weight heparins, graduated
      compression stockings, and early mobilisation when possible. However, the place
      of low molecular weight heparins at high doses and external pneumatic calf
      compression needs to be evaluated by prospective studies.

PMID- 9551349
TI  - [Arterial thrombosis in the course of nephrotic syndrome. Report of three cases].
AB  - Vascular thrombosis remains severe complication in patients with nephrotic
      syndrome. Both venous and arterial thrombosis are observed. We report three new
      cases of arterial thrombosis in patients with nephrotic syndrome. The role of
      acquired hemostasis disorders, inducing hypercoagulability, is predominant.
      Extramembranous glomerulonephritis remains the most frequent cause of nephrotic
      syndrome, complicated by vascular thrombosis. Treatment is based on
      anticoagulation and corticosteroid therapy. Search for proteinuria should be part
      of the etiology work-up in all patients with vascular thrombosis of undetermined
      origin.

PMID- 9551348
TI  - [Carotid endarterectomy using eversion. One year radiologic results].
AB  - A prospective study was done in 100 patients operated on for a stenosis of the
      carotid artery by the eversion endarterectomy method of Van Maele (section
      eversion-anastomosis) between January 1994 and August 1995. Ten patients were
      operated on bilaterally (thus, 110 procedures). The distribution of the patients
      was as follows 81 males and 19 females, mean age 71 years. Clinically, 50
      patients were asymptomatic, 44 stage I, 2 stage II and 4 stage III. Arteriography
      of these patients showed 42 stenoses greater than or equal to 90%, 56 stenoses
      between 70 and 90% and 12 ulcerated plaques (according to the ESCT measurement
      standards). Concerning the supra-aortic vessels, 24 lesions of the vertebral
      subclavian branches and 21 lesions of the intra-cerebral vessels were observed.
      Five endarterectomies out of the 110 (5.4%) could not be performed by this
      eversion method because of the immediate poor technical result before
      angiography. At the end of the procedure digital angiography was performed for
      all the patients who underwent an eversion endarterectomy (105 cases). Six images
      of the internal carotid artery presenting stenoses less than 30% were observed at
      the level of the implantation site. Two narrow stenoses of the distal part of the
      endarterectomy made the interposition of a PTFE graft necessary in 20% of the
      cases, a secondary procedure was necessary after the peri-operative angiography 2
      implantations of PTFE in the internal carotid artery, 8 additional
      endarterectomies of the external carotid artery, 11 infiltrations with
      Papaverine. The immediate post-operative results were 1 death after hemiplegia, 1
      hemiplegia with sequelae (mortality/morbidity approximately 2%, i.e. 2/103
      eversions), 3 regressive hemipareses. Angiographic follow-ups after 1 year were
      performed on 100 out of 110 operated carotid arteries. With regard to the
      internal carotid artery, 4 patients showed a stenosis less than 30%, 1 patient a
      50% stenosis, 1 patient a pre-occlusive stenosis making an operation with the
      interposition of a PTFE graft necessary (restenosis rate after one year 2%). All
      the patients followed after one year remained asymptomatic. Eversion
      endarterectomy is possible for the majority of the atheromatous stenoses of the
      carotid artery (5.4% were not possible for technical reasons). We find this
      method not appropriate when a shunt must be placed. Immediate results are
      comparable to those of classical surgical endarterectomy with or without
      patching. The restenosis rate at 1 year in our series is 2%. This technique
      provides an excellent anatomic result by peri-operative angiography and can
      especially be adapted to stenoses with excess of length of the carotid artery.

PMID- 9551350
TI  - [Complications of vascular surgery].
AB  - Vascular surgery, which in certain life-threatening situations is the only
      possible therapeutic option, has progressed considerably since its beginning in
      the 1950s. Because of the constant progression of vascular diseases, this surgery
      will present, in the forthcoming years, a major public health problem. Because of
      advances in medico-surgical management, evermore elderly and frail patients can
      be treated. Perioperative mortality is constantly decreasing, but much progress
      remains to be accomplished to prevent, avoid or treat, postoperative
      complications. They are common and serious in these typical patients with
      cardiovascular diseases (men over 50 years of age, heavy smokers, atheromatous
      ...). The AA divide these complications into 3 main groups depending on the
      surgical procedure: abdominal aortic surgery, carotid surgery and arterial and
      venous surgery of the lower limbs. There is much data on abdominal aortic surgery
      because these long and complex procedures produce repercussions often involving
      many systems. The postoperative complications are treated according to the system
      they involve: cardiovascular, the most serious, respiratory, the commonest,
      alimentary, neurological, renal, others, as well as combined systems. The AA do
      not deal with the specific problems associated with cardiac and cardio-thoracic
      surgery. The AA discuss the different epidemiological findings of the large
      surgical series published in the 1970s and 1980s. The more recent literature
      analyses the relationship between preoperative risk factors (atheroma, COAD,
      hypertension ...), peroperative problems (surgical difficulties, emergencies,
      massive transfusions, others) and the corresponding postoperative morbidity. Thus
      a few general outlines of the physiopathology of these different complications
      emerge. In the light of these notions the few proposed methods will be evaluated
      in order to improve the preoperative condition of the vascular patient. The AA
      also review the relevance of the preoperative investigation in patients for
      vascular surgery. All these measures aim at reducing the incidence and severity
      of perioperative morbidity.

PMID- 9551351
TI  - [Physiopathologic introduction to anesthesia and resuscitation of the vascular
      patient].
AB  - Coronary artery disease (CAD), arterial hypertension, chronic bronchitis and
      diabetes mellitus are the most frequently encountered diseases complicating the
      clinical course of the vascular patient. Clinical signs of cardiac or pulmonary
      disease are often absent in patients with decreased functional capacity due to
      claudication. For instance, clinical evidence of coronary artery disease was
      found in 36% of patients scheduled for different vascular surgical procedures,
      whereas coronary angiography revealed significant stenoses in as many as 53-68%.
      Patients with chronic hypertensive disease, coronary artery disease and increased
      impedance to left ventricular ejection due to atherosclerosis frequently develop
      impairment of left ventricular (LV) function. Even without clinical or
      radiological evidence, approximately 20-35% of vascular patients have a LV
      ejection fraction below 50% indicating impaired systolic LV function. The
      incidence of diabetes mellitus in vascular surgical patients is around 18%. When
      requiring insulin treatment, diabetes is an independent risk factor for
      postoperative ischemic events and congestive heart failure. Those with autonomic
      neuropathy are often asymptomatic as regards coronary artery disease. Coronary
      artery disease is responsible for over 50% of the immediate, medium- and long
      term mortality and morbidity. Unstable myocardial ischemia, acute myocardial
      infarction which is detected by troponin I and ischemic pulmonary edema are the
      most common immediate postoperative cardiac complications. A large number of
      recent studies, using long-term ECG recording techniques, have allowed more
      accurate estimation of the incidence and time course of perioperative myocardial
      ischemia in vascular surgical patients. The highest incidence of ischemia when
      compared to daily life activities has been noted during the first two days after
      surgery but has been reported to remain elevated even 3-5 days after surgery.
      Interestingly, the incidence of intraoperative ischemia is lower than that
      observed during daily life. Knowledge of the etiology of perioperative myocardial
      infarction is essential if one is to improve cardiac outcome after vascular
      surgery. Many studies have addressed this important field in patients undergoing
      vascular surgery. They have documented a relationship between perioperative
      myocardial ischemia and postoperative myocardial infarction. Although
      postoperative myocardial infarctions are in most cases limited to endocardium
      (non Q wave infarction) they significantly reduce life expectancy of the vascular
      surgical patients. The reduction of cardiac risk following general surgery should
      focus on methods by which the incidence of myocardial ischemia, particularly
      during the postoperative period, could be reduced. These methods include
      intensive intraoperative analgesia or preventive administration of cardiovascular
      treatment which limit postoperative stress: alpha-2 agonists or betablocking
      agents. There are, at present, no studies which convincingly confirm an overall
      decreased mortality if coronary bypass surgery is performed prior to peripheral
      vascular surgery. Although it has been demonstrated that the mortality of the
      peripheral procedure is reduced to approximately one half, the mortality of a
      coronary bypass procedure in vascular surgical patients is five to eight times
      that recorded in a coronary artery bypass population without peripheral vascular
      disease. It remains to be shown if the use of coronary angioplasty prior to
      peripheral vascular surgery can provide a more satisfactory overall outcome.
      Several non-invasive techniques have been suggested to improve the identification
      of high-risk patients undergoing vascular surgery. These tests include exercise
      ECG, ambulatory ECG, dipyridamolethallium scintigraphy and determination of left
      ventricular ejection fraction by gated radionuclide imaging. (ABSTRACT TRUNCATED)

PMID- 9551352
TI  - [Preoperative evaluation of coronary circulation].
AB  - It is not easy to define a plan for the preoperative assessment of the coronary
      circulation: some studies carried out in the context of vascular surgery are
      contradictory and no method has a sensitivity and specificity of 100%.
      Nevertheless, it is essential to select patients with a high risk of
      perioperative cardiac complications so that their medical treatment can be
      reinforced or anatomical correction envisaged. A first assessment is obtained
      from the history, the clinical examination and simple investigations (resting
      ECG, chest X-ray). Surgical operations which do not impose a major strain on the
      cardiovascular system do not require further investigations. The risk of
      postoperative cardiac complications is low in the absence of the nine risk
      factors defined by Goldman and/or an ischemic syndrome (residual angina after
      mild physical activity, unstable angina, myocardial infarct). The problem arises
      in patients with the Goldman risk factors and/or a history of coronary
      insufficiency and/or coronary insufficiency risk factors (diabetes, tobacco,
      hypercholesterolemia, age > 70 years, arterial hypertension), who require an
      operation likely to cause a particularly serious strain on the cardiovascular
      system. An exercise ECG, by the Holter method, is helpful, particularly in known
      or potential coronary arteriopaths who cannot exercise. Echocardiography under
      dobutamine has good sensitivity and good specificity when exercise is impossible.
      Thallium-dipyridamole scanning has not been shown to be helpful in vascular
      surgery. This method could be refined by a quantitative analysis of the number of
      areas and segments involved. Finally, patients showing ischaemic changes on
      continuous ECG recording, abnormalities on echocardiography under dobutamine,
      abnormalities on thallium-dipyridamole myocardial scanning or on exercise ECG,
      should be considered for coronary angiography with a view to a preliminary
      anatomical correction.

PMID- 9551353
TI  - [Perioperative problems posed by patients suffering from vascular diseases. The
      viewpoint of the anesthetist-resuscitator].
AB  - Patients undergoing vascular surgery present a major challenge for the medical
      and surgery teams because patients admitted for vascular surgery frequently have
      other associated disorders. Vital functions must be optimized preoperatively in
      this population. Several problems may arise in the preoperative and postoperative
      periods. The risk of hypothermia or cardiovascular instability and early
      treatment of postoperative complications require careful management. Several
      diagnostic and therapeutic tools are available but their routine use has not
      always been validated by clinical trials in the pathophysiological setting of
      vascular disease. We present several examples of discordance between the
      pathophysiological models and results of clinical studies and raise the question
      of therapeutic objectives.

PMID- 9551355
TI  - [Recurrence of varicosities in the femoral canal following surgery of the
      internal saphenous vein].
AB  - Perforating veins in the femoral canal, which establish a communication, on the
      medial aspect of the thigh, between the deep venous system and: either the trunk
      of the long saphenous vein, single or double, or one or several separate trunks,
      follow three anatomical patterns which clinical examination, phlebography and,
      now, echo-doppler, can identify clearly. When they are incompetent, they increase
      the natural progress of the varicose disease, after surgery of the long saphenous
      vein. Often, they are associated with a redux at the level of the saphenofemoral
      junction and also, sometimes, with an incompetence, primary or recurrent, at the
      short sapheno-popliteal junction, or, furthermore, with an incompetence of the
      medial gastrocnemial veins and their accompanying perforators, within the
      popliteal venous complex. Anastomotic networks between the different superficial
      venous territories in the inguino-genital region, the femoral canal and the
      supero-medial aspect of the leg, explain the cross-evolution between different
      systems. Sclerotherapy is effective when the perforators are not too large and
      their reflux not too important. If it fails, it is necessary to operate after
      precise localization of the sites of reflux through good imaging. A good picture
      is obtained with B mode ultrasound examination and hemodynamic studies with
      pulsed doppler and, even more reliably, with color Doppler. Thus, in recurrences
      in the femoral region, color Doppler will show up certain perforators which,
      despite being dilated, are nevertheless competent and do not need to be dealt
      with.

PMID- 9551354
TI  - [Postoperative recurrence of varicosities at the level of the popliteal fossa.
      Anatomic data guiding the ultrasonographic exploration and surgical sequelae].
AB  - The results of surgery of the short saphenous vein are less consistent than those
      of the long saphenous vein. The difference has been clarified by anatomo-physio
      pathological studies which, as a complement to clinical examination, first used
      the different phlebography techniques and now benefit from pulsed colour
      echodoppler. They have shown that, in varicose veins considered to be of the
      short saphenous system, incompetence at its termination, with its anatomical
      variations, does not account for all the findings. Thus, imaging and the findings
      at surgery, have revealed a genuine venous complex in the popliteal fossa
      situated in four areas: in the sapheno-aponeurotic area with a variable point of
      termination of the short saphenous vein and important tributaries along its
      convexity; in the area of the medial head of the gastocnemius muscle with a
      voluminous trunk formed by the medial gastrocnemial veins which may run towards
      the termination of the short saphenous vein or even drain into its concavity; in
      the deep plane of the popliteal vein, which is sometimes double; in the short
      saphenous network with its very variable vein in the popliteal fossa and the
      lateral gastrocnemial veins. In practice, this classification helps to identify
      congenital reduplications, abnormal of aberrant veins and to perform planned
      surgery aimed at preventing postoperative recurrences. This is so because the
      latter are due, albeit less frequently than at the saphenofemoral junction, to a
      "new vein" which is in fact simply a missed tributary. Recurrences are mainly
      associated with : a duplication of the terminal part of the vein which has been
      missed; a short saphenous stump fed by a trunk from the medial gastrocnemial
      veins which has a termination into the popliteal vein common with the short
      saphenous vein; incompetent large medial gastrocnemial veins draining separately;
      an incompetent popliteal fossa perforator. The last two occur not uncommonly
      together and it has also been noted that failure to strip the short saphenous
      trunk increases the likelihood of postoperative recurrences. Repeat surgery is
      indicated in the presence of recurrences when there are important sources of
      reflux which are fully identified and precisely located by imaging, which is
      essential to prevent recurrent failure.

PMID- 9551356
TI  - [An unusual way of detecting Horton's disease: inflammatory abdominal aortitis].
AB  - We report an original case of giant cell arteritis, revealed by abdominal aortic
      arteritis on CT-scan, which was performed because the patient presented with a
      biological inflammatory syndrome. Course was favorable with steroid therapy. CT
      scan, one month later, demonstrated a stable appearance of both regular and
      concentric thickening of the abdominal aortic wall. Aortic involvement is rare
      and occurs late in the course of giant cell arteritis. Usually clinical and
      biological manifestations of aortitis associated with giant cell arteritis either
      absent or non specific, leading to diagnostic difficulties. Furthermore, aortic
      giant cell arteritis is a major cause of morbidity and mortality. Gravity of
      aortic impairment is mainly linked to the risk of development of aneurysm and/or
      acute dissection. A search for aortic involvement should therefore routinely be
      carried out, once a year, in patients with giant cell arteritis, particularly a
      complete vascular clinical examination and a chest X-ray. Finally, our case
      report suggests that non invasive methods, notably CT-scan, may serve as a
      helpful test in diagnosis and follow-up of aortic giant cell arteritis.

PMID- 9551357
TI  - [Venous thrombosis of the arm consistent with a tumor of the first rib].
AB  - Enchondroma of the first rib is a rare cause of Thoracic Outlet Syndrome (TOS)
      manifested by deep venous thrombosis (DVT). Diagnostic difficulties and
      therapeutic options are discussed. DVT of the upper limb represent 2%-4% of all
      DVT and are divided into primary and secondary. Venous compression represents 8%
      of TOS and generally results from a narrowing of the costo-clavicular space. A
      post-thrombotic syndrome (PTS) is found in 40%-80% despite anticoagulation and
      rest. However following local infusion of thrombolytic agents only 10% of the
      subjects develop PTS. Follow-up studies reveal a complete recanalisation of the
      vein in 45% of the patients treated with thrombolysis, whereas it occurs in only
      4% under anticoagulation alone. This favourable result is obtained at the cost of
      an increased risk of hemorrhagic complications (5%). The solitary enchondroma is
      a benign cartilaginous tumor preferentially localised in the extremities, hands
      and feet. A review of the literature reveals that a total of 40 cases of
      enchondromas have been reported so far, among which 18 were localised in the
      first rib. The proximity of the neuro-vascular elements and a possible malignant
      transformation in 2% of the cases justify the ablation of the tumor. Thrombolysis
      is still highly controversial but gives the best long term prognosis in young
      patients.

PMID- 9551358
TI  - [Is there a specific angiologic reasoning?].

PMID- 9551359
TI  - Activated alpha 2-macroglobulin reverses the immunosuppressive activity in human
      breast cancer cell-conditioned medium by selectively neutralizing transforming
      growth factor-beta in the presence of interleukin-2.
AB  - The immunosuppressive activity of tumor cells may be mediated by tumor-derived
      cytokines such as transforming growth factor-beta (TGF-beta) and interleukin-10
      (IL-10). A human breast cancer cell line derived from malignant ascites (BRC 173)
      secreted TGF-beta, but not IL-10, into tissue culture supernatant (TCS). BRC 173
      TCS suppressed natural killer (NK) and lymphokine-activated killer (LAK) cell
      activity and also blocked the generation of HLA-A*0201-restricted tumor-reactive
      cytotoxic T-lymphocyte (CTL) lines in vitro. Human alpha 2-macroglobulin (alpha
      2M), a plasma protein and cytokine carrier that binds isoforms in the TGF-beta
      family, was tested for its ability to neutralize the immunosuppressive activity
      in BRC 173 TCS. alpha 2M was converted to its activated conformation by reaction
      with methylamine (alpha 2M-MA) and then incubated with normal human peripheral
      blood lymphocytes (PBL) in the presence of IL-2 and BRC 173 TCS. Lysis of NK
      targets (K562) and LAK cell targets (DM6 melanoma) by the PBL was examined after
      6 days of culture. PBL cultured in IL-2, without TCS or alpha 2M-MA, were lytic
      for both target cells. BRC 173 TCS substantially suppressed the lytic activity of
      the PBL in the presence of IL-2. When TGF-beta-neutralizing antibody was added to
      the PBL culture medium with IL-2 and TCS, a majority of the lytic activity was
      restored. alpha 2M-MA (280 nM) neutralized almost all of the immunosuppressive
      activity in the TCS, restoring 80-100% of the lytic activity without any apparent
      effect on the activity of IL-2. The ability of alpha 2M-MA to counteract
      immunosuppressive cytokines in breast cancer TCS was evident in serum-containing
      and serum-free medium. These studies demonstrate the activated alpha 2M can
      function as a selective cytokine neutralizer to thereby promote the activation of
      NK, LAK, and tumor-specific CTL responses.

PMID- 9551360
TI  - Induction of melanoma antigen-specific cytotoxic T lymphocytes in vitro by
      stimulation with B7-expressing human melanoma cell lines.
AB  - Crosslinking of CD28 receptors on resting T lymphocytes by B7 costimulatory
      molecules expressed by antigen-presenting cells (APCs) plays a critical role in T
      cell activation. Human melanomas express major histocompatibility complex (MHC)
      restricted tumor-associated antigens that can be recognized by cytotoxic T
      lymphocytes (CTL), yet they remain poorly immunogenic. One mechanism for the
      failure of T-cell response is the lack of expression of costimulatory molecules
      by human melanoma cells. We have transfected the B7-1 gene into three HLA-A2
      expressing human melanoma cell lines, and studied their capacity to stimulate
      primary human T cells. B7-expressing melanoma cells were excellent inducers of T
      cell proliferation, cytokine production, and cytolytic activity in allogeneic
      mixed lymphocyte cultures through a process dependent on the function of the T
      cell receptor as well as interactions between B7:CD28, CD2:LFA-3, and LFA-1:ICAM
      1. Subset analysis demonstrated that CD4+ T cells or addition of exogenous
      interleukin-2 was required for the induction of CD8+ CTL. Untransfected parental
      melanoma cells were inert as APCs in these cultures. Rotating stimulation of T
      cells with the three B7-expressing cell lines led to the generation of T-cell
      lines that were cytolytic for HLA-A2+ melanoma cells and other HLA-A2+ targets
      that were pulsed with HLA-A2-restricted MART-1 peptides. These data demonstrate
      that expression of B7-1 by human melanoma cells converts them into effective APCs
      for the in vitro induction of MHC-restricted, melanoma-specific CTL.

PMID- 9551362
TI  - Third Keystone Symposium on Cellular Immunology and the Immunotherapy of Cancer.
      Introduction.

PMID- 9551361
TI  - Cyclophosphamide enhances the CTL precursor frequency in mice immunized with MUC1
      mannan fusion protein (M-FP).
AB  - We have previously described the induction of murine CD8+ major
      histocompatibility complex class I restricted cytotoxic T cells to the 20 amino
      acid repeat region of human Mucin 1 (MUC1) variable number of tandem repeats
      region--a mucin greatly increased in expression in breast cancer and proposed as
      a target for immunotherapy. Mannan-MUC1 immunization protocol induces a high
      cytotoxic T lymphocyte (CTL) frequency, and some protection of mice against a
      tumor challenge. The CTL frequency can be substantially increased using
      cyclophosphamide (Cy), from 1/84,900 without Cy to 1/8,100 with Cy. Furthermore,
      in the presence of Cy, established tumors are rapidly eradicated, which does not
      happen in its absence. Cy clearly gives a major increase in the frequency of CTL
      precursors (CTLp) to MUC1 and could be of therapeutic value in patients.

PMID- 9551363
TI  - Tumor vaccines--a reality at last?

PMID- 9551364
TI  - TAP-independent delivery of antigenic peptides to the endoplasmic reticulum:
      therapeutic potential and insights into TAP-dependent antigen processing.
AB  - We have taken several approaches to investigate the capacity of the secretory
      pathway to liberate major histocompatibility complex (MHC) class I-restricted
      antigenic peptides from precursor polypeptides. Cells lacking the peptide
      transporter (TAP) are unable to deliver peptides from cytosolic antigens to class
      I molecules. TAP can be bypassed by targeting peptides directly to the
      endoplasmic reticulum (ER) using NH2-terminal signal sequences. This results in
      the generation of enormous numbers of MHC class I complexes (50,000
      peptides/cell), and recombinant vaccinia viruses expressing such peptides are
      highly immunogenic. In contrast to signal sequence-targeted peptides, peptides
      are liberated very inefficiently from internal locations in ER-targeted full
      length proteins, indicating that the secretory pathway has a limited capacity for
      generating antigenic peptides from most polypeptide contexts. We have, however,
      identified a location in proteins from which peptides can be liberated in
      numerous contexts in the secretory pathway. Placing a number of different
      peptides at the COOH termini of a secreted protein and two proteins with type II
      membrane anchors resulted in their TAP-independent presentation. These findings
      demonstrate that the secretory compartment possesses proteases able to liberate
      COOH-terminal antigenic peptides from virtually any context, entirely consistent
      with a role for these proteases in the processing of TAP-transported antigenic
      peptide precursors.

PMID- 9551365
TI  - Hematopoietic progenitor cells of lymphocytes and dendritic cells.
AB  - Lymphocytes and dendritic cells (DCs) are critical for immune responses, yet how
      they develop from pluripotent hematopoietic stem cells is poorly defined. In
      humans and mice, it is possible to isolate phenotypically defined subsets of bone
      marrow (BM) cells that represent intermediate progenitors without long-term
      repopulating characteristics but with specific lineage differentiation
      properties. For instance, murine BM CD34+ CD45RA+ cells are progenitors for B and
      T lymphocytes with no in vivo repopulation activity. In human BM, a small subset
      (5%) of cells having the phenotype CD34+ Lin- CD10+ CD45RA+ CD38+ Thy-1- c-kit-
      represents a new class of hematopoietic progenitor cells that gives rise to
      lymphocytes [T, B, and natural killer (NK) cells] and to DCs but does not produce
      myeloid or erythroid cells. The identification of such progenitor cells provides
      the opportunity to define the differentiation and growth requirements for the
      production of lymphocytes and DCs. Genes involved in lineage specification can
      also be studied. Altogether, these studies have fundamental implications for
      understanding the biology of pivotal lineages of immune cells. This understanding
      could be used to treat a variety of immunodeficiencies and to design novel
      immunotherapies particularly in the context of hematopoietic cell
      transplantation.

PMID- 9551366
TI  - Chimpanzee dendritic cells derived in vitro from blood monocytes and pulsed with
      antigen elicit specific immune responses in vivo.
AB  - Dendritic cells differentiated in vitro from blood and other sources using
      cytokines hold particular promise as immunotherapeutic agents in cancer. However,
      there are currently no data to show that human in vitro-derived dendritic cells
      are immunogenic in vivo. We have developed a primate model of immunotherapy using
      dendritic cells differentiated in vitro from blood monocytes by culturing with
      human granulocyte/ macrophage colony-stimulating factor and interleukin-4. We
      measured the immune response to antigen elicited by in vitro-derived and antigen
      treated dendritic cells following a single intravenous inoculation an boost in
      chimpanzees. The antigens tested were ovalbumin, a complex foreign protein, and a
      peptide derived from the MUC-1 mucin tumor antigen, a relatively uncomplex self
      antigen. Four chimpanzees were immunized either with antigen-pulsed dendritic
      cells (two animals) or mock-treated dendritic cells (one animal) given
      intravenously or both antigens given in adjuvant subcutaneously (one animal).
      Each animal received a boost of both antigens in adjuvant 10 days later. All
      animals responded with an IgG-mediated humoral response to ovalbumin measured in
      the serum at day 24. This was associated with a proliferative cellular response
      to ovalbumin in the inguinal lymph node draining the boost injection. In
      contrast, antibody responses to mucin peptide were detected in one animal in
      response to the boost injection, and no T cell proliferative responses to mucin
      peptide were detected in the draining lymph node of any animal. To determine if
      the single inoculation of antigen-pulsed dendritic cells elicited any immunity,
      we measured the T cell response to ovalbumin in blood mononuclear cells harvested
      prior to the boost. Ovalbumin-specific proliferative responses that were antigen
      dose dependent were detected in one of two treated animals. In contrast,
      ovalbumin given with adjuvant and mock-treated dendritic cells induced no
      response. The three animals inoculated with dendritic cells, either antigen or
      mock treated, had moderate T cell responses to bovine serum albumin, a
      constituent of the medium used to culture cells prior to injection. We conclude
      from these data that in vitro-derived dendritic cells can elicit T cell responses
      to a complex foreign antigen following a single intravenous injection in a large
      primate. It is likely that immunity to a simple self antigen, MUC-1 mucin
      peptide, may require multiple inoculations. The results support the use of
      dendritic cells differentiated in vitro as vehicles for immunotherapy in humans.

PMID- 9551367
TI  - Autologous human dendriphages pulsed with synthetic or natural tumor peptides
      elicit tumor-specific CTLs in vitro.
AB  - The recent identification of tumor-associated antigens and tumor-associated
      antigen-derived peptide epitopes recognized by cytolytic T lymphocytes (CTLs) in
      the context of major histocompatibility complex (MHC) class I molecules has
      prompted the development of peptide-based vaccines for the treatment of human
      cancers, particularly melanoma. The design of such clinical protocols requires an
      understanding of the inherent immunogenicity of the peptide(s) and a choice of a
      facilitating adjuvant promoting cellular immunity against these peptides. We have
      evaluated the abilities of a series of defined synthetic peptide epitopes derived
      from MART-1/Melan-A, gp100, tyrosinase, and MAGE-3 or unfractionated peptides
      naturally presented by melanoma MHC molecules to elicit HLA-A2-restricted and
      melanoma-reactive CTLs from the peripheral blood of normal donors or patients
      with metastatic melanoma. Autologous peripheral blood dendritic cells (DCs),
      which were easily generated from all donors when cultured in the presence of
      recombinant human interleukin-4 and recombinant human granulocyte-macrophage
      colony-stimulating factor were pulsed with melanoma peptides and used to "prime"
      and/or "boost" CTL cultures in vitro. Our results suggest that antimelanoma CTLs
      may be reproducibly generated in short-term in vitro cultures in this manner
      using either a subset of the defined synthetic peptides (MART-1/Melan-A27-35,
      MART-1/Melan-A32-40, gp100(280-288), tyrosinase368-376, and MAGE-3(271-279)) or
      unfractionated peptides (containing both idiotypic and shared melanoma epitopes)
      derived from freshly isolated autologous melanoma lesions. These in vitro data
      support the use of autologous DCs prepulsed with such peptides as an appropriate
      antigen adjuvant delivery system in melanoma peptide-based vaccines.

PMID- 9551368
TI  - Polycystic ovarian disease: current insights into an old problem.
AB  - Recent studies have led to significant advances in the understanding of the
      pathogenesis of polycystic ovary syndrome (PCOS), as well as to improvements in
      the treatment of the commonly associated symptoms. New data continue to implicate
      etiologic alterations in the hypothalamic-pituitary axis, beginning in the
      perimenarcheal period, as well as derangements in insulin and insulin-like growth
      factor metabolism. Current observations also support a role for an increase in
      adrenal androgen production and an increase in adrenal sensitivity to trophic
      hormone stimulation in the development of PCOS. Therapeutic regimens for those
      patients unsuccessfully treated with traditional approaches have been further
      validated, including the use of flutamide or gonadotropin-releasing hormone
      agonist-steroidal "add back" for the treatment of hirsutism. Novel approaches to
      the treatment of infertility are likewise discussed.

PMID- 9551369
TI  - Progressive virilization of a pubertal phenotypic female: 17 beta-hydroxysteroid
      dehydrogenase deficiency.
AB  - 17 beta-Hydroxysteroid dehydrogenase deficiency is an uncommon inherited disorder
      characterized by genital ambiguity and progressive pubertal virilization. We
      describe the clinical and biochemical features in a 13-year-old 46, XY individual
      who presented with progressive pubertal virilization.

PMID- 9551370
TI  - Teaching pediatric and adolescent gynecology: a pilot study at one institution.
AB  - PURPOSE: To assess resident physicians' clinical recognition skills in Pediatric
      and Adolescent Gynecology. MATERIALS: 1) A questionnaire to identify demographic
      data and self-assessment as to the ability to perform a gynecologic evaluation of
      children. 2) Twenty color photographs of normal genitalia and common gynecologic
      problems in children. PARTICIPANTS: Sixty-one University of Tennessee resident
      physicians; 51 from the Memphis campus--20 obstetrics-gynecology (Ob-Gyn)
      residents, 20 pediatrics residents, and 11 family practice residents--and 10 Ob
      Gyn residents from the Chattanooga campus. MAIN OUTCOME MEASURES: Ability to
      identify normal features of the prepubertal genitalia and to diagnose common
      gynecologic disorders. RESULTS: Ob-Gyn residents from the University of
      Tennessee, Memphis scored significantly better (58.1% correct) than did the other
      three groups; 38.8, 36.9, and 39.1%, respectively (p = .009). Mean performance
      score increased with higher pediatric gynecology PGY levels. PGY-4s performed
      best, whereas PGY-1s scored the lowest, with mean scores of 57.5% and 35.3%,
      respectively (p = .021). Residents who reported having a well-defined program in
      pediatric gynecology scored significantly better than those who did not have such
      a program, 55.3% and 39.5%, respectively (p < .001). CONCLUSIONS: A well-defined
      program in pediatric gynecology enhances resident education and provides them
      with better tools to perform gynecologic evaluations of children and adolescents.

PMID- 9551371
TI  - Pubertal metrorrhagia.
AB  - OBJECTIVE: To determine the clinical characteristics of pubertal metrorrhagia and
      its treatment, depending on severity; to evaluate the frequency of etiologies and
      the influence of hemostatic abnormalities; and to describe severe pubertal
      metrorrhagia. Design, setting and participants. This retrospective study examined
      all the files (n = 105) of adolescents presenting for pediatric gynecology
      consultation at a children's hospital between January 1979 and June 1993.
      RESULTS: The mean age of patients at the first consultation was 13 years.
      Metrorrhagia began in the year after the first menstrual period in 85% of cases.
      The causes were functional (83 cases), primary hemostatic disorder (14 cases),
      hemostatic disorder secondary to renal or hepatic disease (7 cases), or tumor (1
      case). The cases were assigned to one of three groups, according to the severity
      of anemia; group I, mild anemia, hemoglobin Hb > 11 g%, 64 cases; group II,
      moderate anemia, Hb 8-11 g%, 23 cases; and group III, severe anemia, Hb < 8 g%,
      18 cases. Of the 14 patients suffering from primary hemostatic disorders, 7 had
      been diagnosed before the onset of metrorrhagia; the disorder was revealed by the
      metrorrhagia in the remaining 7. Only 1 of these patients was severely anemic
      (known factor X deficiency). Four patients suffering from moderate von
      Willebrand's disease were discovered after specific tests; they were mildly or
      moderately anemic. The severe anemias (group III) all occurred during the first
      three periods. This group had functional disorders in 15 of 18 cases. Treatment
      continued to be required in 10 of 18 cases followed for more than 3 years.
      Treatment was progestin for group I and II patients or an estroprogestin,
      followed by a progestin, for group III. Curettage was never required.
      CONCLUSIONS: The most common cause of pubertal metrorrhagia is a functional
      disorder (80% of cases). Hemostatic disorders likely to cause severe menstrual
      hemorrhage were known before the age of menarche; these disorders must be
      controlled by hormone treatment begun before or at the time of the first
      menstrual period. Severe forms that arise during the initial three menstrual
      cycles are functional in most cases. These should be given a course of treatment
      lasting several years. There is a high risk of recurrence. Treatment is medical
      and hormonal in all cases.

PMID- 9551372
TI  - Young adults' knowledge, attitudes, and behavior about abortions in young women.
AB  - OBJECTIVE: To document opinions and decision-making strategies of young adults
      regarding abortions for young women. METHODS: Eighty-nine male and 215 female
      college students completed a questionnaire on abortion during routine visits to
      their university health center. RESULTS: Among the salient findings, most
      respondents took a pro-abortion stance for girls under 18 in cases of rape (92%
      of students), incest (90%), or danger to the girl's health (90%). A much lower
      priority was given for abortion in cases of fetal abnormalities (55% of
      students), economic hardship (51%), or for girls who were married (55%). Abortion
      was considered acceptable regardless of circumstances by 46% of students and
      never a good idea by 18%. The outcome of unplanned pregnancies for minors should
      be decided by the girl (90% of students), partner (55%), parents (29%), and state
      or federal law (8%). Abortions for minors should require parental notification
      (45%) or consent (33%). Although only one student felt illegal abortions were
      safe, 19% would seek this kind of abortion and 4% of females would try to cause
      their own miscarriage if abortions were outlawed in the United States.
      CONCLUSIONS: The vast majority of young adults believed that girls under 18
      should retain the right to decide the outcome of their pregnancy and should not
      be subjected to governmental restrictions. The highest priority for abortion was
      given to girls who had been victimized or whose health was at risk. Although
      nearly all respondents are aware of the hazards of criminal abortions, many would
      resort to such unsafe practices if legal alternatives were no longer available.

PMID- 9551373
TI  - Abortion trends in Singapore: a 25-year review.
AB  - STUDY OBJECTIVE: Abortion legislation in Singapore has gone through dramatic
      changes in the past 25 years. In this paper, we studied the effect of abortion
      legislation on abortion trends in Singapore. SETTING AND PARTICIPANTS: The
      Ministry of Health, Singapore, collects data on all abortions performed in
      Singapore. These data have been analyzed and are presented in this paper.
      RESULTS: The liberalization of abortion legislation resulted in a dramatic
      increase in the number of abortions performed beginning in 1974. The rate peaked
      at 23,512 abortions in 1985, and in fact, 35% of all pregnancies were terminated
      in 1985. The introduction of mandatory abortion counseling in 1986 resulted in a
      decline in the number of abortions to 16,476 in 1993 with only 24.6% of
      pregnancies being terminated. The teenage abortion rate was 0.2 per 1000 female
      teenagers under 20 years of age in 1970. With the liberalization of abortions,
      the rate reached a peak of 13.7 per 1000 female teenagers in 1985. In 1993, the
      teenage abortion rate was 9.5%. The proportion of nulliparous women seeking
      abortion has increased phenomenally from 0.5% in 1976 to 40.6% in 1993. Close to
      95% of the women seeking abortions in 1993 did so for social reasons, 3.7% for
      medical reasons, and 2.0% for failed contraception (Table 3). CONCLUSION:
      Mandatory abortion counseling and a change in the government policy which now
      encourages Singaporeans to have more children if they can afford it, have
      resulted in a decrease in the number of abortions being performed. The problems
      of teenage abortions, nulliparous abortions, and repeated abortions need to be
      further addressed.

PMID- 9551374
TI  - Cavernous lymphangioma presenting as a vaginal discharge in a six-year-old
      female: a case report.
AB  - STUDY OBJECTIVE: This case report is written to describe a new and unusual
      presentation of retroperitoneal cavernous lymphangioma. INTERVENTIONS: A large
      cystic abdominal mass was discovered during an examination under anesthesia to
      evaluate a vaginal discharge in a 6-year-old girl. The mass was diagnosed by
      computed tomography (CT) and removed via laparotomy with argon beam coagulation
      of smaller cystic lesions. RESULTS: Six months postoperatively, the patient had a
      negligible amount of vaginal discharge. CONCLUSIONS: Cavernous lymphangioma
      should be considered as a rare cause of vaginal discharge in young females.

PMID- 9551375
TI  - At what age should a virginal adolescent have her first pelvic examination?

PMID- 9551376
TI  - What is your diagnosis? Subungual squamous cell carcinoma.

PMID- 9551377
TI  - Feline chronic renal failure: calcium homeostasis in 80 cases diagnosed between
      1992 and 1995.
AB  - Eighty cats with chronic renal failure (CRF) were evaluated in a prospective
      study to investigate the prevalence and aetiopathogenesis of renal secondary
      hyperparathyroidism (RHPTH), using routine plasma biochemistry and assays of
      parathyroid hormone (PTH), blood ionised calcium and 1,25
      dihydroxycholecalciferol (1,25[OH]2D3). Hyperparathyroidism was a frequent
      sequela of CRF, affecting 84 per cent of cats with CRF, the severity and
      prevalence of RHPTH increasing with the degree of renal dysfunction. Compared
      with an age-matched control population, plasma concentrations of phosphate and
      PTH were significantly higher and 1,25(OH)2D3 concentrations were significantly
      lower in the two groups of cats presenting with clinical signs of CRF.
      Significant ionised hypocalcaemia was present only in cats with end-stage renal
      failure. However, a number of cats were hyperparathyroid in the absence of
      abnormalities in the parameters of calcium homeostasis measured in this study.
      There was a significant correlation between plasma phosphate and PTH
      concentrations.

PMID- 9551378
TI  - Technique of lateral canthoplasty for the correction of macropalpebral fissure in
      the dog.
AB  - The various clinical anomalies associated with macropalpebral fissure in the dog
      can be relatively successfully addressed by a reduction in functional eyelid
      length and stabilisation of the lateral canthus. In this new technique the basic
      principles of the Kuhnt-Szymanowski lateral canthoplasty have been extended to
      include an additional shortening of the upper eyelid obtained by a triangular
      split thickness resection. Results in a series of 22 patients have demonstrated
      significant clinical improvement throughout, with optimum positioning of the
      modified palpebral fissures being achieved in five of these patients by the
      additional and subsequent resection of redundant forehead skin.

PMID- 9551379
TI  - Salivary gland necrosis in dogs: a retrospective study of 19 cases.
AB  - Salivary gland necrosis has been described in dogs and is characterised by
      enlarged, hard, painful salivary glands, retching and vomiting or regurgitation.
      The cause has yet to be determined. A retrospective study of 19 dogs with the
      same clinical signs was undertaken for breed, age, gender, history and presenting
      signs, diagnostic evaluations and findings, treatment and outcome. An underlying
      association was identified in 16 of the 19 dogs. This included Spirocerca lupi
      infestation (seven dogs), megaoesophagus (three dogs) and oesophagitis,
      oesophageal diverticulum, giardiasis and suspected autoimmune sialadenitis.
      Almost all associated lesions involved the oesophagus. Where the associated
      disease was successfully treated, the salivary glands returned to normal and all
      clinical signs resolved. It is hypothesised that an afferent vagal reflex may be
      involved, and that the mechanism of disease is similar to the neural pathogenesis
      suggested for hypertrophic osteopathy; in this instance, the efferent targets are
      the salivary glands rather than the limbs.

PMID- 9551380
TI  - Use of milbemycin oxime in the treatment of dogs with nasal mite (Pneumonyssoides
      caninum) infection.
AB  - Clinical diagnosis of canine nasal mite (Pneumonyssoides caninum) infection is
      difficult due to the mite's location in the caudal nasal cavity and frontal
      sinuses. The current study was performed to evaluate the efficacy of milbemycin
      oxime in treating dogs with nasal mite infection. A prospective open uncontrolled
      study included 20 dogs with case histories indicating possible nasal mite
      infection. Inclusion criteria consisted of either nasal mites being demonstrated
      (group 1, four dogs), or suspicious clinical signs with no other apparent causes,
      combined with eosinophilia (group 2, 16 dogs). Milbemycin oxime 1 mg/kg was given
      orally three times at 10-day intervals. In 17 (85 per cent) dogs, clinical signs
      resolved completely following milbemycin therapy; within 10 days of the first
      treatment in 13 cases (group 1, four dogs; group 2, nine dogs) and within 14 days
      in four cases. In the remaining three dogs clinical signs persisted but were
      diminished.

PMID- 9551381
TI  - Management of disc-associated wobbler syndrome with a partial slot fenestration
      and position screw technique.
AB  - A previously unpublished surgical technique for the management of disc-associated
      wobbler syndrome is described. A series of 17 middle-aged dobermanns (mean age
      7.4 years) with this condition were managed by a technique of partial slot
      fenestration and position screw fixation of the affected disc space (C6/7 in all
      cases). One patient was lost to follow-up and, of the remaining 16 cases, 13
      improved following surgery (81 per cent). The three failures were a consequence
      of incorrect placement of one of the screws. Careful evaluation of immediate
      postoperative radiographs allows this problem to be identified; the screw can
      then be correctly repositioned with an immediate return to surgery.

PMID- 9551382
TI  - Familial cutaneous vasculopathy and demodicosis in a German shepherd dog.
AB  - A two-month-old female German shepherd dog was presented with a history of
      ulcerated central pads of all four feet. On physical examination, the footpads
      were swollen, soft and ulcerated. On the nasal planum there was a partially
      depigmented nodule. Multiple biopsies were taken from the cutaneous lesions and
      histological examination revealed focal collagen degeneration and vasculitis. A
      diagnosis of familial cutaneous vasculopathy was made. Seven months later the
      nasal nodule had disappeared and the footpads were still swollen but non
      ulcerated. At this time, the dog manifested a generalised pustular demodicosis.

PMID- 9551383
TI  - Prostatic carcinoma in two cats.
AB  - Clinical, radiological and pathological features of two cats with prostatic
      carcinoma are reported. In both cats the presenting history included signs of
      lower urinary tract disease with haematuria and dysuria. Prostatomegaly was
      visible radiographically in one cat; an irregular intraprostatic urethra was seen
      on retrograde contrast urethrography in both cats. In one of the cats, neoplasia
      was suspected on the basis of a transurethral catheter biopsy. Following a poor
      response to palliative treatment in both cases, euthanasia was performed with
      histological confirmation of the diagnosis.

PMID- 9551385
TI  - Cat scratch disease.

PMID- 9551384
TI  - Emphysematous cystitis and bladder trigone diverticulum in a dog.
AB  - A 14-month-old, male German shepherd dog was evaluated for chronic, recurrent
      Escherichia coli urinary tract infection. An initial diagnosis of emphysematous
      cystitis was made, which resolved with appropriate antibacterial therapy. The
      urinary tract infection, however, did not resolve and on further investigation a
      bladder trigone diverticulum was evident, thought to be congenital in origin.
      This report describes the apparent ultrasonographic and radiological changes, and
      surgical repair of the diverticulum, and reviews the literature with regard to
      both congenital bladder trigone diverticulum and emphysematous cystitis. The
      former has never been documented in the dog and the latter is an unusual finding
      in a non-diabetic dog.

PMID- 9551386
TI  - Intestinal permeability in canine SIBO.

PMID- 9551387
TI  - Meta-analysis as a clinical tool in nephrology.

PMID- 9551388
TI  - Renal microvascular assembly and repair: power and promise of molecular
      definition.
AB  - Developmental assembly of the renal microcirculation is a precise and coordinated
      process now accessible to experimental scrutiny. Although definition of the
      cellular and molecular determinants is incomplete, recent findings have reframed
      concepts and questions about the origins of vascular cells in the glomerulus and
      the molecules that direct cell recruitment, specialization and morphogenesis. New
      findings illustrate principles that may be applied to defining critical steps in
      microvascular repair following glomerular injury. Developmental assembly of
      endothelial, mesangial and epithelial cells into glomerular capillaries requires
      that a coordinated, temporally defined series of steps occur in an anatomically
      ordered sequence. Recent evidence shows that both vasculogenic and angiogenic
      processes participate. Local signals direct cell migration, proliferation,
      differentiation, cell-cell recognition, formation of intercellular connections,
      and morphogenesis. Growth factor receptor tyrosine kinases on vascular cells are
      important mediators of many of these events. Cultured cell systems have suggested
      that basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and
      vascular endothelial growth factor (VEGF) promote endothelial cell proliferation,
      migration or morphogenesis, while genetic deletion experiments have defined an
      important role for PDGF beta receptors and platelet-derived growth factor (PDGF)
      B in glomerular development. Receptor tyrosine kinases that convey non
      proliferative signals also contribute in kidney and other sites. The EphB1
      receptor, one of a diverse class of Eph receptors implicated in neural cell
      targeting, directs renal endothelial migration, cell-cell recognition and
      assembly, and is expressed with its ligand in developing glomeruli. Endothelial
      TIE2 receptors bind angiopoietins (1 and 2), the products of adjacent supportive
      cells, to signals direct capillary maturation in a sequence that defines
      cooperative roles for cells of different lineages. Ultimately, definition of the
      cellular steps and molecular sequence that direct microvascular cell assembly
      promises to identify therapeutic targets for repair and adaptive remodeling of
      injured glomeruli.

PMID- 9551389
TI  - Genetic studies into inherited and sporadic hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) in adults carries a high morbidity and mortality,
      and its cause remains unknown despite many theories. Although familial HUS is
      rare, it affords a unique opportunity to elucidate underlying mechanisms that may
      have relevance to acquired HUS. We have undertaken a genetic linkage study based
      on a candidate gene approach. A common area bounded by the markers D1S212 and
      D1S306, a distance of 26 cM located at 1q32 segregated with the disease (Z max
      3.94). We demonstrate that the gene for factor H lies within the region.
      Subsequent mutation analysis of the factor H gene has revealed two mutations in
      patients with HUS. In an individual with the sporadic/relapsing form of the
      disease we have found a mutation comprising a deletion, subsequent frame shift
      and premature stop codon leading to half normal levels of serum factor H. In one
      of the three families there is a point mutation in exon 20 causing an arginine to
      glycine change, which is likely to alter structure and hence function of the
      factor H protein. Factor H is a major plasma protein that plays a critical
      regulatory role in the alternative pathway of complement activation. In light of
      these findings and previous reports of HUS in patients with factor H deficiency,
      we postulate that abnormalities of factor H may be involved in the etiology of
      HUS.

PMID- 9551390
TI  - Dysregulation of cytokine expression in tubulointerstitial nephritis associated
      with murine malaria.
AB  - We examined the circulating levels of the proinflammatory cytokines tumor
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, IL-6, granulocyte
      macrophage-colony stimulating factor (GM-CSF), and the anti-inflammatory cytokine
      IL-10, and their expression in kidneys acutely infected with murine malaria
      parasite P. berghei ANKA in C57BL/6J mice. Groups of six mice sacrificed on days
      5, 10, 15, and 20, and normal controls were used for cytokine analysis. High
      concentrations of TNF-alpha and IL-10 were detected in plasma as shown by ELISA,
      and elevated levels of mRNA specific for TNF-alpha and IL-10 in infected kidneys
      were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR)
      analysis. Kidney sections stained with antibodies against TNF-alpha, IL-1 alpha,
      IL-6, GM-CSF and IL-10 for immunohistochemistry showed markedly enhanced staining
      for TNF-alpha, and progressively increased staining for IL-1 alpha and IL-6 both
      in the tubules and the walls of arteries during the course of infection. The
      endothelia of blood vessels and inflammatory cells located around small arteries
      showed positive staining for GM-CSF from day 10 onwards. Unlike the staining for
      proinflammatory cytokines, the anti-inflammatory cytokine IL-10 showed strongly
      positive staining in normal tubules and walls of arteries, especially in the
      brush border of proximal tubules, but the staining intensity decreased
      dramatically after day 15 post-infection. A strongly positive correlation was
      found between the antibody staining for TNF-alpha/IL-1 alpha in tubules, and the
      severity of proteinuria. In contrast, there was an inverse correlation between
      the staining for IL-10 with TNF-alpha/IL-1 alpha, and the degree of proteinuria.
      Plenty of pigmented macrophages showed positive staining both for proinflammatory
      and anti-inflammatory cytokines in the tubulointerstitium. Our findings imply
      that the up-regulation of proinflammatory cytokines and the dysregulation of anti
      inflammatory cytokines are involved in the pathogenesis of tubulointerstitial
      nephritis associated with malaria.

PMID- 9551391
TI  - Expression of connective tissue growth factor in human renal fibrosis.
AB  - Chronic renal failure may occur in etiologically diverse renal diseases and can
      be caused by hemodynamic, immunologic and metabolic factors. Initial damage may
      evoke irreversible scarring, which involves production of a number of
      proinflammatory and fibrogenic cytokines, including platelet-derived growth
      factor (PDGF) and transforming growth factor beta (TGF-beta). Connective tissue
      growth factor (CTGF), a cytokine of the family of growth regulators comprising
      sef10, cyr61, CTGF and nov, has recently been described in association with
      scleroderma and other scarring conditions. We investigated CTGF mRNA expression
      in 65 human renal biopsy specimens of various renal diseases by in situ
      hybridization. In control human kidney CTFG mRNA was mainly expressed in visceral
      epithelial cells, parietal epithelial cells, and some interstitial cells.
      Connective tissue growth factor was strongly up-regulated in the extracapillary
      and severe mesangial proliferative lesions of crescentic glomerulonephritis, IgA
      nephropathy, focal and segmental glomerulosclerosis and diabetic nephropathy. An
      increase in the number of cells expressing CTGF mRNA was observed at sites of
      chronic tubulointerstitial damage, which correlated with the degree of damage. in
      the tubulointerstitial area the majority of the CTGF mRNA positive cells
      coexpressed alpha-smooth muscle actin, and were negative for macrophage markers.
      Our results indicate that CTGF may be a common growth factor involved in renal
      fibrosis.

PMID- 9551392
TI  - Estrogen induces glomerulosclerosis in analbuminemic rats.
AB  - Progression of chronic renal disease is usually more rapid in males, both in
      humans and in experimental animals. Estrogen-replacement studies indicate that
      this may be related to the beneficial effects of estrogen on the lipoprotein
      profile. However, in hyperlipidemic analbuminemic rats (NAR), females are more
      prone to develop renal injury than males, and ovariectomy tends to decrease
      triglyceride levels and prevent renal disease. Therefore, we studied the effects
      of estrogen administration on lipoproteins, and the induction of renal injury in
      uninephrectomized female and male NAR. Ovariectomized and orchidectomized
      uninephrectomized NAR were treated with estradiol implants for 24 weeks. In an
      additional group of ovariectomized rats, the implant was removed after 12 weeks.
      Both in ovariectomized and orchidectomized NAR, estradiol caused severe
      hypercholesterolemia (9 to 12 mmol/liter) and hypertriglyceridemia (6 to 8
      mmol/liter) after six weeks. Subsequently, these rats developed severe
      proteinuria, reaching 209 +/- 25 and 95 +/- 43 mg/day, respectively, after 24
      weeks. At this point there was severe glomerular sclerosis, with a respective
      score of 107 +/- 21 and 61 +/- 33. In terminal blood samples the most pronounced
      increase in lipid levels were observed in very low density lipoproteins (VLDL),
      intermediate density lipoproteins (IDL) and low density lipoproteins (LDL). In
      contrast, ovariectomized NAR and orchidectomized NAR without exogenous estrogen
      had much lower lipid levels (cholesterol 5 to 7 mmol/liter and triglycerides 1 to
      2 mmol/liter) after six weeks. These rats, or ovariectomized NAR where the
      estrogen treatment had been withdrawn, had practically no proteinuria (4 +/- 1,
      19 +/- 11, and 13 +/- 4 mg/day, respectively) or renal damage (glomerulosclerosis
      score 1 +/- 0.4, 5 +/- 3 and 3 +/- 1, respectively) after 24 weeks. Thus, in
      hypertriglyceridemic analbuminemic rats, estrogen-treatment causes further
      increases in both triglycerides and cholesterol. Most probably these changes
      contribute to the development of renal injury by estrogen in this model. This
      effect of estrogen, which has also been observed in the Zucker rat, is unique for
      the hypertriglyceridemic state and deserves further study.

PMID- 9551393
TI  - Glomerular expression of p27Kip1 in diabetic db/db mouse: role of hyperglycemia.
AB  - Early diabetic nephropathy is characterized by glomerular hypertrophy. Previous
      studies in vitro have demonstrated that mesangial cells exposed to high glucose
      are arrested in the G1-phase of the cell cycle and express increased levels of
      the cyclin-dependent kinase inhibitor p27Kip1. The present study was performed to
      investigate the renal expression of p27Kip1 in db/db mice, a model of diabetes
      mellitus type II. Glomerular p27Kip1 protein, but not mRNA expression, was
      strongly enhanced in diabetic db/db mice compared with non-diabetic db/+
      littermates. Immunohistochemical studies revealed that this stimulated expression
      was mainly restricted to the nuclei of mesangial cells and podocytes, but
      glomerular endothelial cells occasionally also stained positively. Quantification
      of p27Kip1 positive glomerular cells showed a significant increase of these cells
      in db/db mice compared with non-diabetic db/+ animals. Although tubular cells
      revealed a positive staining for p27Kip1 protein, there was no difference between
      db/+ and db/db mice. Immunoprecipitation experiments revealed that p27Kip1
      protein associates with Cdk2 and Cdk4, but not with Cdk6. To test for the
      influence of hyperglycemia on cell cycle arrest and p27Kip1 expression, mesangial
      cells were isolated from db/+ and db/db mice. There was a similar basal
      proliferation when these cells were grown in normal glucose-containing medium
      (100 mg/dl). However, raising the glucose concentration to 275 to 450 mg/dl
      induced cell cycle arrest in db/+ as well as db/db mesangial cells. Increasing
      the medium osmolarity with D-mannitol failed to induce p27Kip1 expression in
      mesangial cells. Transfection of cells with p27Kip1 antisense, but not missense,
      phosphorothioate oligonucleotides facilitated cell cycle progression equally well
      in db/+ and db/db mesangial cells. Furthermore, p27Kip1 expression was comparable
      in both cell lines in normal glucose, but increased in high glucose medium. Our
      studies demonstrate that p27Kip1 expression is enhanced in diabetic db/db
      animals. This induction appears to be due to hyperglycemia. Expression of p27Kip1
      may be important in cell cycle arrest and hypertrophy of mesangial cells during
      early diabetic nephropathy.

PMID- 9551394
TI  - Mesangiolytic glomerulopathy in severe congestive heart failure.
AB  - To study the glomerular morphological abnormalities in congestive heart failure
      (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their
      mean age was 59 years, and they showed mild prerenal azotemia. They had generally
      been treated with digitalis and diuretics, and a few of them with captopril or
      nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and
      mesangial thickening were observed at high frequencies (61%, 64%, and 57%,
      respectively). They characteristically showed mesangiolysis (ML) by the findings
      of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular
      matrix and poor matrix area. In addition, glomerular infiltration of mononuclear
      leukocytes including macrophages was noted in 70% of the cases. Glomerular
      enlargement was not correlated with the grade of hyperemia, but it was correlated
      with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p <
      0.004). There was an inverse relationship between the grades of mesangial
      thickening and of the ML index (P < 0.005). The number of glomerular leukocytes
      was positively correlated with mean glomerular size (P < 0.002) and with the ML
      index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a
      prominently higher mean ML index than the negative cases (P < 0.005). There was
      an inverse correlation between the mean glomerular size and the partial oxygen
      pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between
      the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases
      positive for mesangiolytic mesangial degeneration showed significantly lower PaO2
      values than the cases negative for this lesion (P < 0.04). In the analysis of the
      various causes of CHF, the patients with congenital cardiac anomalies showed mean
      levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and
      histologically the largest mean glomerular size (P < 0.04). There was no
      difference in the ML index and the glomerular leukocyte number among the
      subgroups classified by the causes. These results indicate that ML associated
      with glomerular enlargement is the major glomerular abnormality characteristic in
      patients with severe CHF and suggest that glomerular infiltration of leukocytes,
      especially of macrophages, should play an important role in the progression of
      both ML and glomerulomegaly. The contributions of persistent hypoxia and up
      regulated angiotensin II as the causative factors of these glomerular
      abnormalities in congestive heart failure are discussed.

PMID- 9551395
TI  - Expression of the cyclin kinase inhibitor, p27kip1, in developing and mature
      human kidney.
AB  - It has been shown that glomerular visceral epithelial cells (VEC) proliferate
      during glomerulogenesis, but differentiated VEC of the fetal kidney do not. It is
      also recognized that the proliferative capacity of the VEC in mature kidneys is
      very limited, and according to some investigators, may be completely absent. The
      basis for this remains unknown. Cell proliferation is controlled by cell cycle
      related proteins, of which one class, the cyclin kinase inhibitors (CKI), cause
      cell cycle arrest and inhibit proliferation. A role for CKI in kidney development
      is not known. Accordingly, we examined the expression of the CKI p27kip1 (p27) in
      developing and mature human kidney tissue. Concomitant expression of markers of
      cell proliferation, Ki-67-related antigen (Ki-67) and proliferating cell nuclear
      antigen (PCNA), also were examined in fetal and mature human kidney tissue by
      immunocytochemical techniques. In developing kidney, Ki-67 and PCNA expression
      are most pronounced in the nephrogenic zone where expression correlates inversely
      with increasing glomerular maturation. In well-differentiated glomeruli, Ki-67
      and PCNA expression is present in some parietal epithelial cells but is absent in
      the VEC. In contrast, p27 staining exhibits a reverse gradient of expression. p27
      is absent in the proliferating tissue exhibiting the earliest stages of
      differentiation, whereas expression is widespread in the differentiated
      epithelial cells of more mature glomeruli, in which detectable cell proliferation
      has ceased. Expression of p27 was not identified in fetal mesangial or glomerular
      endothelial cells. In the mature human kidney, the pattern of p27 expression
      identified in differentiated fetal glomeruli persists and appears to be
      constitutive and specific for glomerular VEC. This pattern of p27 expression in
      terminally differentiated VEC may explain their limited proliferative capacity in
      response to injury. This is the first demonstration of a potential role for p27
      in human renal development.

PMID- 9551396
TI  - Accelerated apoptosis characterizes cyclosporine-associated interstitial
      fibrosis.
AB  - Recently we developed a model of cyclosporine nephropathy in rats characterized
      by tubulointerstitial (TI) injury, macrophage infiltration, and progressive
      interstitial fibrosis [1, 2]. To determine if the TI injury accompanying
      cyclosporine A (CsA) nephropathy was associated with accelerated apoptosis and
      ischemia, we treated rats for five weeks with CsA with or without losartan (to
      block angiotensin II type 1 receptor), or hydralazine/furosemide (H/F) (protocol
      #1). In protocol #2, rats received CsA with or without L-NAME (to block nitric
      oxide) or L-arginine (to provide a precursor to nitric oxide formation).
      Cyclosporine A treated rats had increased apoptosis of tubular and interstitial
      cells documented by PAS, propidium iodide staining, TUNEL assay, and electron
      microscopy compared to vehicle treated controls. Macrophages containing apoptotic
      cells could be confirmed by TUNEL/ED-1 doublestaining and colocalized in areas of
      TI injury. Animals treated with CsA + losartan had a statistically significant
      decrease in apoptosis (TUNEL + cells/mm2) when compared to CsA treated animals
      (6.0 vs. 19.9, P < or = 0.0001). The decrease in apoptosis in the CsA + H/F group
      was not statistically significant. Animals treated with CsA + L-NAME had a
      statistically significant increase in apoptosis compared to the CsA treated
      animals (12.3 vs. 6.4, P = 0.001). L-arginine administration with CsA resulted in
      a decrease in tubulointerstitial apoptosis versus CsA treated animals, however,
      this did not reach statistical significance. The addition of L-arginine did
      result in a significant reduction in interstitial fibrosis (P < 0.0001).
      Regression analysis revealed a significant correlation between apoptosis and
      interstitial fibrosis in both protocols. (CsA vs. CsA + losartan r = 0.63, P <
      0.0001; CsA vs. CsA + L-NAME r = 0.83, P < 0.0001). We conclude that CsA
      nephropathy is associated with a marked increase in apoptosis of tubular and
      interstitial cells. Cyclosporine A induced apoptosis is partially mediated by
      angiotensin II and nitric oxide inhibition, suggesting a role for renal ischemia
      in this process, and CsA induced apoptosis correlates with interstitial fibrosis.

PMID- 9551397
TI  - Adhesion molecules and urinary tumor necrosis factor-alpha in idiopathic
      membranous glomerulonephritis.
AB  - Adhesion molecules are required in several physiological processes, but their
      altered function/expression is associated with the pathogenesis of inflammatory
      diseases. In the present study on idiopathic membranous glomerulonephritis (MGN)
      the expression of adhesion molecules (ICAM-1, VCAM-1, PECAM-1, E-selectin, LFA-1,
      Mac-1) was analyzed in different cellular compartments of the kidney using an
      indirect immunoperoxidase technique and monoclonal antibodies. Relationships
      between the expression of these molecules and the clinical and morphological
      activity of the disease and the urinary excretion of tumor necrosis factor alpha
      (TNF-alpha) were studied in 20 patients. The results were compared with the
      findings in ten normal kidneys and urinary TNF-alpha in 17 healthy subjects. The
      expression of adhesion molecules in glomeruli and tubules was unchanged apart
      from a diminished expression of VCAM-1 (P = 0.014) in glomerular parietal
      epithelial cells and PECAM-1 in glomerular endothelial cells (P < 0.01).
      Interstitial peritubular capillaries expressed significantly (P = 0.009) more E
      selectin compared with the controls. The interstitial compartment had a highly
      increased number of cells expressing ICAM-1 in MGN (32.4 +/- 4.6 cells/high power
      field) compared with the controls (9.4 +/- 1.2; P < 0.001). Also, cells
      expressing VCAM-1 (10.2 +/- 1.6 vs. 2.8 +/- 1.9; P = 0.005). PECAM-1 (25.9 +/-
      5.3 vs. 7.4 +/- 2.1; P = 0.006), and LFA-1 (20.4 +/- 3.6 vs. 8.3 +/- 1.5; P =
      0.041) were increased in the interstitium. Proteinuria correlated particularly
      with the expression of E-selectin in peritubular capillaries (r = 0.63, P =
      0.004). The number of LFA-1 expressing inflammatory cells in the interstitium
      correlated with peritubular capillary E-selectin (r = 0.8, P < 0.001) and
      interstitial ICAM-1 (r = 0.61, P = 0.009) expression, but histological
      alterations did not correlate with the expression of adhesion molecules. Tumor
      necrosis factor-alpha excretion was significantly increased in MGN (41 +/- 8
      pg/mg creatinine) compared with the controls (13 +/- 2; P = 0.001), and in
      particular, it correlated with the interstitial expression of LFA-1 (r = 0.71, P
      = 0.002). This study suggests that active MGN leads not only to proteinuria but
      also to increased urinary TNF-alpha excretion. These may serve as triggers for
      the up-regulation of adhesion molecules in the peritubular capillaries and
      interstitial cells thus enhancing the development of the interstitial injury.

PMID- 9551398
TI  - Podocytes undergo phenotypic changes and express macrophagic-associated markers
      in idiopathic collapsing glomerulopathy.
AB  - Collapsing glomerulopathy (CG), a severe form of focal segmental
      glomerulosclerosis (FSG), is characterized by tuft retraction and consolidation
      in numerous glomeruli and changes in podocyte morphology and topography. Other
      glomeruli are less affected. Collapsing glomerulopathy is also characterized by
      tubulointerstitial atrophy and fibrosis. The pathophysiology of the glomerular
      and tubulointerstitial lesions is poorly understood. We studied renal tissue of
      five Black and three White patients, all human immuno-deficiency virus (HIV)
      negative, with nephrotic syndrome, renal failure, and histological evidence of
      CG. Immunohistochemistry identified normal podocyte phenotypes by podocalyxin,
      vimentin and complement receptor 1 (CR1) labeling. Three monoclonal antibodies
      were used to further characterize podocyte epitopes: anti-CD68 clone KP1, anti
      CD68 clone PG-M1 and anti-M130 clone M18 (Ber-MAC3). Light microscopy of
      collapsed glomeruli showed podocyte swelling, vacuolization, multinucleation,
      "cobblestone-like" alignment around the glomerular tuft, and pseudo-crescent
      formation in Bowman's space. In collapsed glomeruli, podocalyxin, vimentin and
      CR1 labeling tagged both normal and vacuolated podocytes still attached to the
      GBM, but labeling was not found in cobblestone-like podocytes or in podocytes
      detached from the GBM. Conversely, numerous podocytes undergoing detachment and
      shedding into Bowman's space expressed macrophagic-associated epitopes. Cells
      with macrophagic-associated epitopes clumped in cystically dilated tubules and
      were aligned in tubules of smaller caliber. Their appearance was that of viable
      cells. There was no morphologic indication that these cells expressing macrophage
      associated antigens originated from outside the glomeruli or outside the tubules.
      We conclude that in CG podocytes detach from the GBM, lose their normal podocytic
      phenotype and acquire macrophage differentiation antigens. The presence of cells
      with such antigens in tubular lumens suggests that detached metaplastic podocytes
      progress along the tubule or, alternatively, that CG tubular cells also undergo
      metaplastic changes into macrophage-like cells.

PMID- 9551399
TI  - Subtractive hybridization cloning: an efficient technique to detect overexpressed
      mRNAs in diabetic nephropathy.

PMID- 9551400
TI  - Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2.
AB  - Nitric oxide is synthesized in experimental immune complex glomerulonephritis due
      to local induction of type 2 nitric oxide synthase (NOS2). To determine the role
      of NOS2, the course of accelerated anti-glomerular basement membrane
      glomerulonephritis (anti-GBM) was examined in mice homozygous for disruption of
      the NOS2 gene compared with heterozygous littermates. Disease in the wild type
      strain (129Sv) was characterized by heavy albuminuria, glomerular neutrophil and
      macrophage infiltration and glomerular thrombosis. NOS2, interleukin 1B (IL-1
      beta) and tumor necrosis factor alpha (TNF alpha) mRNA were induced by 24 hours.
      The NOS2-deficient mutant mice and the heterozygous mice displayed early (24 hr)
      and full autologous phase (day 6) injury indistinguishable from the wild-type
      mice. The equivalent degree of albuminuria and glomerular inflammation indicates
      that NOS2 does not play an essential role in this form of glomerulonephritis in
      the mouse.

PMID- 9551401
TI  - Accelerated fibrosis and collagen deposition develop in the renal interstitium of
      angiotensin type 2 receptor null mutant mice during ureteral obstruction.
AB  - We examined the role of angiotensin in renal remodeling that is specifically
      channeled through the angiotensin type 2 receptor (AT2 receptor). Previously, we
      observed that in mouse embryonic kidneys the AT2 mRNA is predominantly expressed
      in the mesenchyme. We therefore chose a model of unilateral ureteral obstruction,
      characterized by activation of the renin-angiotensin system, while fibrosis
      develops prominently within the renal interstitium. Male wild-type mice (Agtr2 
      /Y) and mice null mutant for the AT2 gene (Agtr2 -/Y) were subjected to a
      complete unilateral ureteral ligation for 5 or 14 days. Obstructed kidneys of
      Agtr2 -/Y mice showed more severe interstitial fibrosis than those of Agtr2 +/Y
      mice, confirmed by increased collagen by point-counting on Masson trichrome
      stained sections, and increased alpha 1(I) collagen mRNA expression by Northern
      blot. Immunohistochemistry staining for PCNA (a marker of cell proliferation),
      F4/80 (a marker of macrophages), vimentin (a marker of fibroblasts), and alpha
      SMA (a marker of myofibroblasts) revealed that, while the two groups were
      comparable in the degree of cell proliferation and macrophage infiltration,
      fibroblasts/ myofibroblasts were present in a greater abundance in obstructed
      kidneys of Agtr2 -/Y mice than in Agtr2 +/Y at both 5 and 14 days after
      obstruction. Moreover, cells undergoing apoptosis were significantly less in
      Agtr2 -/Y than in Agtr2 +/Y. Thus, the AT2 receptor significantly impacts the
      remodeling process within renal interstitium, potentially by regulating the
      population of collagen-producing cells.

PMID- 9551402
TI  - Na/H exchange and H-K ATPase increase distal tubule acidification in chronic
      alkalosis.
AB  - We examined whether H(+)-ATPase, H(+)-K(+)-ATPase, and or Na+/H+ exchange
      mediates increased distal tubule acidification in animals with chronic metabolic
      alkalosis using pharmacological inhibitors of these H+ transporters in in vivo
      perfused tubules of anesthetized rats. Chronic metabolic alkalosis was induced
      with furosemide followed by minimum electrolyte diet and HCO3 drinking water. The
      reduction in net HCO3 reabsorption was greater in distal tubules of alkalotic
      compared to control animals perfused with Schering 28080 to inhibit H(+)-K(+)
      ATPase (-6.4 +/- 0.9 vs. -1.4 +/- 0.5 pmol/mm.min-1, P < 0.02) and with EIPA to
      inhibit Na+/H+ exchange (-11.1 +/- 1.7 vs. -6.6 +/- 0.9 pmol/mm.min-1, P < 0.01)
      but was similar in distal tubules of alkalotic and control animals perfused with
      bafilomycin to inhibit H(+)-ATPase. The greater reduction of distal tubule net
      HCO3 reabsorption in alkalotic compared to control animals induced by EIPA was
      eliminated by systemic infusion of the endothelin receptor antagonist bosentan (
      4.6 +/- 0.7 vs. -4.4 +/- 0.7 pmol/mm.min-1, P = NS) but the greater reduction
      induced by Schering 28080 persisted. Urine endothelin-1 (ET-1) excretion was
      higher in animals with maintained alkalosis (164.5 +/- 23.7 vs. 76.6 +/- 10.8
      fmol/day, P < 0.03), but decreased following KCl repletion to a value (86.7 +/-
      10.0 fmol/day, P < 0.02 vs. respective before-KCl value) that was not different
      from that for KCl-repleted control animals (79.9 +/- 8.7 fmol/day, P = NS vs. KCl
      repleted alkalotic animals). The data support that augmented distal tubule
      acidification in alkalotic animals is due to increased H(+)-K(+)-ATPase and
      Na+/H+ exchange activity, the latter stimulated by endogenous endothelins.

PMID- 9551403
TI  - Control of calcium oxalate crystal structure and cell adherence by urinary
      macromolecules.
AB  - Crystal polymorphism is exhibited by calcium oxalates in nephrolithiasis, and we
      have proposed that a shift in the preferred crystalline form of calcium oxalate
      (CaOx) from monohydrate (COM) to dihydrate (COD) induced by urinary
      macromolecules reduces crystal attachment to epithelial cell surfaces, thus
      potentially inhibiting a critical step in the genesis of kidney stones. We have
      tested the validity of this hypothesis by studying both the binding of
      monohydrate and dihydrate crystals to renal tubule cells and the effect of
      macromolecular urinary solutes on crystal structure. Renal tubule cells grown in
      culture bound 50% more CaOx monohydrate than dihydrate crystals of comparable
      size. The effects of macromolecules on the spontaneous nucleation of CaOx were
      examined in HEPES-buffered saline solutions containing Ca2+ and C2O4(2-) at
      physiologic concentrations and supersaturation. Many naturally occurring
      macromolecules known to be inhibitors of crystallization, specifically
      osteopontin, nephrocalcin and urinary prothrombin fragment 1, were found to favor
      the formation of calcium oxalate dihydrate in this in vitro system, while other
      polymers did not affect CaOx crystal structure. Thus, the natural defense against
      nephrolithiasis may include impeding crystal attachment by an effect of
      macromolecular inhibitors on the preferred CaOx crystal structure that forms in
      urine.

PMID- 9551405
TI  - Contribution of endothelin receptors in renal microvessels in acute cyclosporine
      mediated vasoconstriction in rats.
AB  - Cyclosporine A (CsA), a widely used immunosuppressive agent, causes renal
      vasoconstriction and systemic hypertension. Recent data suggest that the renal
      effect of CsA is possibly mediated by endothelin (ET). We investigated the
      effects of CsA on renal microvessels and the efficacy of ETA or ETA/ETB receptor
      antagonists in ameliorating CsA effects in the hydronephrotic rat kidney.
      Infusion of CsA (30 mg.kg-1) induced a transient increase (20%) in mean arterial
      pressure (MAP) and a sustained reduction (85%) in glomerular blood flow (GBF) due
      to preferential constriction of the arcuate artery (39%) and the proximal segment
      of the interlobular artery (23%). Under basal conditions the ETA receptor
      antagonist BQ-123 had marginal effects consisting of reduction in MAP, rise in
      GBF and dilation of preglomerular vessels. The non-selective ETA/ETB receptor
      antagonist PD 145065 also reduced MAP, but tended to decrease GBF and constrict
      large preglomerular vessels. The difference in effects of the two antagonists
      indicated that under basal conditions ETB blockade constricts large preglomerular
      vessels and reduces GBF. After BQ-123 or PD 145065, the constriction of large
      preglomerular vessels and reduction in GBF induced by CsA was attenuated by about
      50%, but the rise in MAP was not influenced. Our data indicate that a sizable
      part of renal vasoconstriction due to CsA is mediated via ET production in large
      preglomerular arteries and can be avoided by the blockade of ETA receptors.
      Additional blockade of ETB receptors does not attenuate the CsA effects further,
      possibly because ETB receptors mediate both vasoconstriction and dilation.

PMID- 9551404
TI  - The Na(+)-K(+)-ATPase beta 1 subunit is associated with the HK alpha 2 protein in
      the rat kidney.
AB  - The Na-K-ATPase beta 1 subunit acts as the beta subunit for the HK alpha 2
      protein in the rat kidney. The colonic H(+)-K(+)-ATPase is a member of the P-type
      ATPases, and has been shown to contribute to potassium transport by the mammalian
      kidney and colon. The P-type ATPases often consist of an alpha subunit that
      contains the catalytic site and a beta subunit that participates in regulation of
      enzyme activity and targeting of the enzyme to the plasma membrane. The cDNA of
      the alpha subunit (HK alpha 2) has been cloned and the HK alpha 2 protein has
      been isolated from the rat kidney and colon. However, a unique beta subunit for
      the colonic H(+)-K(+)-ATPase has not been described. To determine if one of the
      known beta subunits present in the kidney might act as the beta subunit for the
      colonic H(+)-K(+)-ATPase, microsomes enriched in the colonic H(+)-K(+)-ATPase
      were isolated using an HK alpha 2-specific antibody (AS 31.7) and the Minimac
      magnetic separation system. Immunoblots of rat kidney microsomal protein isolated
      with antibody AS 31.7 were probed with antibodies directed against the gastric HK
      beta subunit, Na(+)-K(+)-ATPase alpha 1, and Na(+)-K(+)-ATPase beta 1 subunits. A
      band of the appropriate size was detected with Na(+)-K(+)-ATPase beta 1-specific
      antibodies, but not those directed against HK beta 1. These data suggest that
      Na(+)-K(+)-ATPase beta 1 could be the beta subunit for the colonic H(+)-K(+)
      ATPase in the kidney.

PMID- 9551406
TI  - Basic fibroblast growth factor is a morphogenic modulator in kidney vessel
      development.
AB  - During kidney organogenesis the development of renal vessels must be synchronized
      with the maturation of nephrons and the collecting duct system. Several reports
      showed that hormones and mitogenic peptides as basic fibroblast growth factor
      (bFGF) or vascular endothelial growth factor (VEGF) are involved in this
      regulatory process. It is a known fact that bFGF receptors are expressed by
      differentiating tubular epithelium and mesenchyme, but little information is
      available about the function of bFGF in kidney organogenesis. The role of bFGF
      during kidney development was investigated using an organotypic culture system
      and immunohistological techniques. Renal cortex explants were prepared from the
      kidneys of neonatal rabbits with a microsurgical method, retaining the natural
      tissue composition. The explants were cultured serum free under continuous medium
      perfusion. Our results indicate a new and unexpected role of bFGF during the
      differentiation process. When bFGF alone was applied, vessels could no longer be
      detected. The inhibitory influence of bFGF could be overcome by addition of VEGF
      or hormones such as retinoic acid and aldosterone/vitamin D3. The combination of
      these factors with bFGF resulted in the expression of small vessel-like
      structures. We conclude that bFGF has a morphogenic rather than a mitogenic
      function during kidney vessel development.

PMID- 9551407
TI  - Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial
      cells.
AB  - Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from
      human pheochromocytoma, is present in the kidney and secreted from endothelial
      cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM
      is still unclear. To clarify the significance of AM as a local regulator, we
      investigated its secretion and action in cultured cells, and examined the effects
      of neutralization using a specific monoclonal antibody against AM. The prepared
      antibody directed against the ring structure showed a high affinity for human and
      rat AM. Using radioimmunoassay with this antibody, we found significant secretion
      from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from
      EC and VSMC. The addition of AM into cultured cells dose-dependently increased
      cAMP production and potently inhibited PDGF-stimulated thymidine incorporation.
      Pretreatment with the monoclonal antibody completely abolished cAMP increase
      induced by exogenous AM. Moreover, antibody neutralization of endogenously
      secreted AM in cultured EC, but not in MC or VSMC, markedly (by approximately
      70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA
      synthesis. These results indicate that AM, acting as an autocrine/paracrine
      regulator, exerts an antiproliferative action on EC and MC, and suggest its role
      as a local modulator of endothelial and mesangial function.

PMID- 9551408
TI  - Angiotensin converting enzyme inhibitor-induced renal dysfunction in
      atherosclerotic renovascular disease.
AB  - Ischemic nephropathy due to bilateral renovascular disease (RVD) is increasingly
      recognized as cause of end-stage renal failure in the elderly, but a reliable non
      invasive method of detection is nor available. Angiotensin converting enzyme
      inhibition (ACEi) may impair renal function in such patients, but a prospective
      study of its diagnostic validity has not been undertaken. We studied the effects
      of controlled exposure to ACEi on plasma creatinine in 108 patients at risk for
      severe bilateral atherosclerotic RVD, and compared the findings with subsequent
      angiography. ACEi was given for two weeks, or, to avoid acute renal failure, for
      four days if plasma creatinine had increased by 20% or more. If after two weeks
      of ACEi plasma creatinine had not increased by > or = 20%, while blood pressure
      was still elevated, plasma creatinine was remeasured after blood pressure control
      by addition of diuretics. The severity of RVD was scored by the stenosis grade of
      the best perfused kidney. Fifty-two patients had severe bilateral RVD, defined as
      > or = 50% stenosis to both kidneys (N = 23) or a solitary functioning kidney (N
      = 29). Of the others, 21 had less severe bilateral RVD, 20 unilateral RVD, and 15
      no apparent RVD. Basal plasma creatinine was higher in severe bilateral RVD
      (median 170 mumol/liter, range 85 to 654 mumol/liter) than in the others (122
      mumol/liter, 62 to 675 mumol/liter; P < 0.01), but not discriminative due to a
      large variability. The increase during ACEi was correlated with the degree of RVD
      (r = 0.53, P < 0.001). In 69 patients ACEi caused at least a 20% increase in
      plasma creatinine, in 26 cases by four days, in 31 after two weeks, and in 12
      only after blood pressure control by diuretics. Among these were all 52 patients
      with severe bilateral RVD, 15 of the 41 patients with lesser forms of RVD, and
      two with normal renal arteries. Thus, in this selected population the criterion
      of > or = 20% rise in plasma creatinine upon ACEi was 100% sensitive to detect
      severe bilateral RVD, while its specificity was 70%. No case of acute renal
      failure was encountered, and plasma creatinine always recovered after stopping
      ACEi. In conclusion, controlled exposure to ACEi in these patients is safe, and
      ACEi-induced increase in plasma creatinine is a very sensitive detector of severe
      bilateral RVD in a high risk population.

PMID- 9551409
TI  - Increased VLDL in nephrotic patients results from a decreased catabolism while
      increased LDL results from increased synthesis.
AB  - Increased very low density lipoprotein (VLDL) in nephrotic patients results from
      a decreased catabolism while increased low density lipoprotein (LDL) results from
      increased synthesis. Hyperlipidemia is a hallmark of nephrotic syndrome that has
      been associated with increased risk for ischemic heart disease as well as a loss
      of renal function in these patients. The hyperlipidemia usually is characterized
      by increased cholesterol levels, although hypertriglyceridemia may be present as
      well. The factors that determine the phenotype of nephrotic dyslipidemia are not
      understood, nor has the primary stimulus for nephrotic hyperlipidemia been
      identified. One hypothesis is that nephrotic hyperlipidemia is the result of a
      coordinate increase in synthesis of proteins by the liver. To address these
      issues we simultaneously measured the in vivo rate of VLDL apolipoprotein B100
      (apo B100) secretion, LDL apo B100 synthesis and albumin synthesis in patients
      with a nephrotic syndrome (N = 8) and compared them with a control group (N = 7)
      using a primed/continuous infusion of the stable isotope L-[1-13C] valine for six
      hours. Kinetic data were analyzed by multicompartmental analysis. Patients
      studied had combined hyperlipidemia as reflected by an significant increase in
      both VLDL and LDL apo B100 pool sizes. In contrast, the albumin pool size was
      significantly decreased. VLDL apo B100 levels were primarily increased as a
      consequence of a decrease in fractional catabolic rate (FCR) rather than from an
      increase in the absolute synthesis rate (ASR). Both VLDL apo B100 and
      triglycerides were inversely related to the fractional catabolism (FCR) of VLDL
      apo B100 (r2 = 0.708; P = 0.0088) while neither had any relationship to the ASR
      of VLDL apo B100. In contrast to VLDL, increased LDL apo B100 was not a
      consequence of decreased catabolism. The LDL apo B100 ASR was significantly
      increased (P = 0.001) in the nephrotic patients compared to controls. Low density
      lipoprotein apo B100 ASR was greater than that of VLDL apo B100 in some patients,
      suggesting that LDL in these patients was not only derived from VLDL
      delipidation, but also by an alternative secretory pathway. There was no clear
      relationship between the ASR of VLDL apo B100 and the ASR of albumin within the
      current study population. Our data indicate that increased VLDL in nephrotic
      patients results from a decreased catabolism, while increased LDL results from
      increased synthesis.

PMID- 9551410
TI  - Angiotensin converting enzyme gene polymorphism and ACE inhibition in diabetic
      nephropathy.
AB  - The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in
      insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy
      varies considerably. Therefore, we tested the potential role of an insertion
      (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric
      responsiveness in an observational follow-up study. Sixty (II, N = 13; ID, N = 26
      and DD, N = 21) young hypertensive IDDM patients suffering from diabetic
      nephropathy were investigated during three months before and for the initial six
      month period during ACE inhibition [captopril 44 (SD 22) mg/24 hr, no differences
      in drug dose between groups]. Blood pressure (MABP) and albuminuria (ELISA) were
      measured three (1 to 6) times before and three (1 to 13) times during ACE
      inhibition. At baseline the groups (II/ID/DD) had comparable (1) mean arterial
      blood pressure (MABP mm Hg) of 113 +/- 10/108 +/- 9/114 +/- 8, (2) albuminuria
      (geometric mean with 95% CI) 1394 (747 to 2608)/1176 (844 to 1797) and 1261 (827
      to 2017) mg/24 hr, and (3) serum creatinine (geometric mean with 95% CI), 80 (68
      to 93)/85 (76 to 97)/103 (85 to 119) mumol/liter, respectively. Angiotensin
      converting enzyme inhibition induced a significant reduction in MABP, albuminuria
      and kidney function in all three groups (II/ID/DD; P < 0.05): (1) MABP (mean +/-
      SD) 12 +/- 7/5 +/- 7/8 +/- 9 mm Hg (ANOVA, P = 0.02); (2) albuminuria [mean (95%
      CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, P < 0.01); and (3)
      increasing serum creatinine [mean (95% CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) %
      (ANOVA, NS), respectively. Adjusting for differences in reduction in MABP did not
      change the association between decrease in albuminuria and ACE/ID genotypes (P <
      0.01). A multiple linear regression analysis revealed that the ACE/ID
      polymorphism, albuminuria and MABP at baseline independently influenced the
      decline in albuminuria after initiation of ACE inhibition (R2 = 0.21, P < 0.01).
      A significant association between changes in MABP and albuminuria was
      demonstrated (R2 = 0.16, P < 0.01). Our data show that hypertensive albuminuric
      IDDM patients with the II genotype are particularly susceptible to commonly
      advocated renoprotective treatment.

PMID- 9551411
TI  - Involvement of interleukin-8 in dialysis-related arthritis.
AB  - To elucidate the role of interleukin (IL)-8, a chemotactic factor for
      neutrophils, in dialysis-related arthritis (DRA) of patients on long-term
      hemodialysis, the concentration of IL-8 was measured in the synovial fluids of
      DRA patients with acute arthralgia and joint swelling, and was compared with
      those in patients with rheumatoid arthritis (RA) and patients with osteoarthritis
      (OA). We noted a marked elevation of IL-8 in the joint fluids of patients with
      DRA and RA as compared with OA. Furthermore, to determine the role of IL-8 in
      synovitis, we examined the in vivo effect of intra-articular injection of human
      recombinant IL-8 on leukocyte infiltration into the joint space of rabbits. A
      single injection of IL-8 to the joints of rabbits induced rapid infiltration of
      neutrophils into the joint space and synovial tissues, which reached a maximum in
      four hours. The oral administration of indometacin farnesil (a prodrug that is
      converted to indomethacin after intestinal absorption) before the injection of IL
      8 alleviated the infiltration of neutrophils. When human synovial cells were
      incubated with tumor necrosis factor (TNF)-alpha, the expression of IL-8 mRNA and
      IL-8 production in the cultured synovial cells were increased. The TNF-alpha
      stimulated expression of IL-8 mRNA and IL-8 production in the cultured synovial
      cells were markedly inhibited by dexamethasone. In conclusion, IL-8 levels were
      markedly elevated in the joint fluids of patients with DRA. Interleukin-8
      released from synovial cells may be an important factor to induce acute
      inflammation in DRA. Dexamethasone and indomethacin may be effective for DRA by
      inhibiting the production and chemotactic actions of IL-8, respectively.

PMID- 9551412
TI  - Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport
      during long CAPD dwells.
AB  - Addition of the nitric oxide (NO) donor nitroprusside to 1.36% glucose dialysate
      enlarges the effective peritoneal surface area during four-hour dwells. The
      theoretical positive effect on ultrafiltration is, however, counteracted by an
      increase in glucose absorption. The absorption of the glucose polymer icodextrin
      is much lower in comparison with glucose-based dialysis solutions, due to its
      high molecular weight. In the present study 7.5% icodextrin dialysis solution
      with and without the addition of 4.5 mg/liter nitroprusside was studied during
      eight-hour CAPD dwells. Two Standard Peritoneal permeability Analyses, adapted
      for eight-hour dwells, were performed in 10 stable CAPD patients. Nitrate and
      cGMP were measured as parameters of NO synthesis. The transcapillary
      ultrafiltration increased in a linear way with icodextrin (ICO) and was even
      higher after the addition of nitroprusside (NP): 666 (ICO) versus 834 (NP) ml/8
      hr, P = 0.03. The effective lymphatic absorption rate was not different. The
      resulting net ultrafiltration increased with nitroprusside: 344 (ICO) versus 540
      (NP) ml/8 hr, P < 0.01. The mass transfer area coefficient of urea increased 15%
      and that of creatinine 26% with nitroprusside, consistent with the expected
      enlargement of the vascular peritoneal surface area. The increase in protein
      clearances was more pronounced the larger the protein: beta 2-microglobulin 19%,
      albumin 47%, IgG 63% and alpha 2-macroglobulin 95%. Dialysate/plasma (D/P) ratios
      of nitrate were not higher than the expected values on the basis of its molecular
      weight (P < 0.001). They increased 19% with nitroprusside. Also, the D/P ratio
      cyclic guanosine monophosphate (cGMP) after four hours increased with
      nitroprusside (0.39, range 0.13 to 0.55 ICO, and 0.82, range 0.36 to 1.39 NP, P =
      0.01). With nitroprusside the D/P ratio cGMP was higher than expected after four
      and eight hours (P < 0.001). This points to local generation of NO after addition
      of nitroprusside. The nitroprusside induced increase in the mass transfer area
      coefficients (MTAC) of creatinine and in the ultrafiltration caused an increase
      in the creatinine clearance from 4.2 ml/min to 5.0 ml/min during the eight-hour
      dwell. This means that nitroprusside adds 3 liters/week to the peritoneal
      clearance of creatinine. The adequacy of peritoneal dialysis can therefore be
      improved by the addition of nitroprusside to 7.5% icodextrin, used for the long
      exchange.

PMID- 9551413
TI  - Universal precautions prevent hepatitis C virus transmission: a 54 month follow
      up of the Belgian Multicenter Study. The Universitaires Cliniques St-Luc (UCL)
      Collaborative Group.
AB  - The isolation of anti-hepatitis C virus (HCV) in hemodialyzed (HD) patients has
      been repeatedly advocated to prevent nosocomial HCV transmission. We evaluated
      the incidence of seroconversion for HCV in Belgian HD patients, and demonstrate
      the complete prevention of HCV transmission by adherence to the universal
      precautions advocated by the Centers for Disease Control (Atlanta, GA, USA). All
      (N = 963) HD patients from 15 units, none of which isolates anti-HCV positive
      patients, were tested by a second or third generation enzyme-linked immunosorbent
      assay (with confirmation by a second- or third-generation recombinant immunoblot
      assay or the polymerase chain reaction) every 18 months from May 1991 to November
      1995. Follow-up was available in 488 patients (drop-outs resulting from death or
      transplantation mainly). The yearly incidence of seroconversion for HCV over the
      initial 18 months was 1.41%, with evidence suggestive of nosocomial HCV
      transmission. Universal precautions were therefore reinforced. The incidence of
      seroconversion subsequently fell to 0.56% and 0%, respectively (P = 0.014),
      despite the facts that the average transfusion load and the proportion of
      patients with dialyzer reuse or with monitors disinfected after each session did
      not change significantly. We conclude that the strict enforcement of universal
      precautions fully prevents HCV transmission to HD patients. The isolation of anti
      HCV positive patients is not warranted.

PMID- 9551414
TI  - Anaphylactoid reactions during hemodialysis in sheep are ACE inhibitor dose
      dependent and mediated by bradykinin.
AB  - Anaphylactoid reactions (AR) have been attributed to the generation of bradykinin
      (BK) when AN69 membranes are used together with angiotensin converting enzyme
      (ACE) inhibitors during hemodialysis. However, conclusive evidence for the
      involvement of the BK as the mediator of these AR is still lacking. This study
      examined the degree of contact activation in an animal model caused by three PAN
      membranes--AN69, PAN DX, and SPAN- and the effects of different doses of the ACE
      inhibitor enalapril (ENA) and the BK B2-receptor antagonist icatibant on AR
      during hemodialysis. Six sheep were dialyzed for one hour with or without ENA pre
      treatment using the different membranes in random order. Severe AR were observed
      only during hemodialysis with AN69 dialyzers together with ENA pre-treatment; the
      severity of AR increased with the ENA dose. Mild hypotension was noted during
      hemodialysis with AN69 without ACE inhibition and with PAN DX and 20 mg ENA.
      Compared to pre-dialysis values, maximum generation of BK after blood passage
      through the dialyzer was found at five minutes: 73-fold (AN69 without ENA), 161
      fold (AN69 with 10 mg ENA), 97-fold (AN69 with 20 mg ENA), 108-fold (AN69 with 30
      mg ENA), 154-fold (AN69 with 30 mg ENA and 0.1 mg/kg icatibant), 18-fold (PAN DX
      without ENA), and 42-fold (PAN DX with 20 mg ENA). Elevated BK levels in arterial
      blood were detected during hemodialysis with AN69 membranes even without ACE
      inhibition (2.5-fold); pre-treatment with 20 mg ENA further increased arterial BK
      concentrations (4-fold). Furthermore, a marked decline of prekallikrein and high
      molecular weight kininogen concentrations was noted for both AN69 and PAN DX
      membranes. Anaphylactoid reactions during hemodialysis were completely prevented
      by icatibant even after pre-treatment with ENA and in the presence of high BK
      concentrations. Concentrations of prekallikrein, high molecular weight kininogen,
      and BK remained unchanged and no AR were observed during hemodialysis with SPAN
      and pre-treatment with 20 mg ENA. Our findings confirm that AR during
      hemodialysis with the negatively charged AN69 membrane are mediated by BK, since
      they can be prevented by the BK B2-receptor antagonist icatibant.

PMID- 9551415
TI  - Identification of operational clues to dry weight prescription in hemodialysis
      using bioimpedance vector analysis. The Italian Hemodialysis-Bioelectrical
      Impedance Analysis (HD-BIA) Study Group.
AB  - In patients undergoing hemodialysis (HD) cyclic body fluid changes are estimated
      by body weight variations, which may be misleading. Conventional bioelectrical
      impedance analysis (BIA) produces biased estimates of fluids in HD due to the
      assumption of constant tissue hydration. We used an assumption-free assessment of
      hydration based on direct measurements of the impedance vector. The impedance
      vector (standard BIA at 50 kHz frequency) was measured in 1367 HD patients, ages
      16 to 89 years with BMI 17 to 31 kg/m2, 1116 asymptomatic (680 M and 436 F), and
      251 with recurrent HD hypotension (118 M and 133 F) before and after two HD
      sessions (thrice weekly bicarbonate dialysis, 210 to 240 min) removing 2.7 kg
      fluid. The vector distribution of HD patients was compared to 726 healthy
      subjects with the same age and BMI range. Individual vector measurements
      (resistance and reactance components) were plotted on the gender specific 50th,
      75th and 95th percentiles of the vector distribution in the healthy population
      (reference tolerance ellipses) as a resistance-reactance graph (RXc graph). The
      wet-dry weight cycling of HD patients was represented on the resistance-reactance
      plane with a definite, cyclical, backward-forward displacement of the impedance
      vector. The vectors of patients with HD hypotension were less steep and more
      often shifted to the right, out of the reference 75% tolerance ellipse, than
      asymptomatic patients. A wet-dry weight prescription, based on BIA indications,
      would bring the vectors of patients back into the 75% reference ellipse, where
      tissue electrical conductivity is restored. Whether HD patients with vector
      cycling within the normal third quartile ellipse have better outcome awaits
      confirmation by longitudinal evaluation.

PMID- 9551416
TI  - Rapid activation of the complement system by cuprophane depends on complement
      component C4.
AB  - Hemodialysis with cuprophane dialyzer membranes promotes rapid activation of the
      complement system, which is thought to be mediated by the alternative pathway.
      Complete hereditary deficiency of complement C4, a classical pathway component,
      in two hemodialysis patients provided the opportunity to investigate a possible
      role of the classical pathway. In two hemodialysis patients with both C4
      isotypes, C4A and C4B, and in one patient with C4B deficiency complement
      activation occurred immediately after the onset of hemodialysis, with peak levels
      of C3a and terminal complement complex (TCC) after ten to fifteen minutes. In
      patients with complete C4 deficiency, C3a and TCC remained unchanged for fifteen
      minutes and increased thereafter, reaching the highest level after thirty
      minutes. The leukocyte nadir was also delayed from fifteen to thirty minutes. In
      vitro incubation of normal, C4A- or C4B-deficient serum with cuprophane caused
      complement activation after fifteen minutes. In contrast, no activation was
      observed in sera of four C4-deficient patients. The addition of normal serum or
      purified human C4 restored the capacity for rapid complement activation. In one
      patient with severe immunoglobulin deficiency, C3a and TCC levels increased only
      moderately after 25 minutes of cuprophane dialysis. This patient's serum also
      exhibited delayed complement activation in vitro, which was normalized after
      pretreatment of cuprophane with immunoglobulins. Preincubation of normal serum
      with MgEGTA, a blocker of the classical pathway, inhibited rapid complement
      activation through cuprophane. As basal levels of C4a are markedly increased in
      hemodialysis patients (3450 +/- 850 ng/ml) compared to healthy controls (224 +/-
      81 ng/ml), no further elevation of C4a was detectable during cuprophane
      hemodialysis. Incubation of normal serum with cuprophane, however, caused a
      slight increase in C4a after five minutes. These results indicate that the
      initial deposition of complement C3b on the cuprophane membrane, necessary for
      activation of the amplification loop of the alternative pathway, is mediated by
      the classical pathway C3-convertase C4b2a. We propose an extended concept of
      complement activation through cuprophane, which is based on four steps: (a)
      binding of anti-polysaccharide antibodies, (b) classical pathway activation, (c)
      alternative pathway activation and (d) terminal pathway activation.

PMID- 9551417
TI  - Effect of on-line conductivity plasma ultrafiltrate kinetic modeling on
      cardiovascular stability of hemodialysis patients.
AB  - The aim of this multicenter, prospective, randomized cross-over study was to
      clarify whether on-line conductivity ultrafiltrate kinetic modeling (treatment
      B), as a substitute for sodium kinetic modeling, is capable of reducing
      intradialytic cardiovascular instability in comparison with standard treatment
      (treatment A), by reducing the sodium balance variability. Both treatments were
      performed by means of a modified hemodiafiltration technique. Treatment A was
      performed using fixed dialysate conductivity; treatment B made use of the
      dialysate conductivity derived from a conductivity kinetic model, in order to
      obtain an end-dialysis ultrafiltrate conductivity at each dialysis session that
      was equal to the mean value determined in the same patient during the four-week
      run-in period. Thus, during treatment B, the expected end-dialysis ultrafiltrate
      conductivity value of each patient should have been constant. The study was
      carried out according to a multicenter cross-over design of 16 weeks with two
      treatments (A or B), two sequences (1 = ABB and 2 = BAA), a run-in period of four
      weeks (period 1, treatment A), and three consecutive experimental periods of four
      weeks each. Analysis of variance for a cross-over design was used for the
      statistical analysis. Forty-nine hemodialysis patients prone to intradialytic
      hypotension (> 25% of sessions) were enrolled from 16 participating centers, and
      randomly assigned to either sequence 1 (26 patients) or sequence 2 (23 patients).
      Six patients dropped out and four were protocol violators, which left 39 patients
      selected for statistical analysis. There was no difference in the average
      dialysate conductivity, predialysis and end-dialysis plasma water ultrafiltrate
      conductivity or body weight between treatment A and treatment B. Thus, the
      observed mean sodium balance was not different and, as expected, only the intra
      patient variability of end-dialysis ultrafiltrate conductivity (index of sodium
      balance variability) was reduced (21%). During treatment A, systolic blood
      pressure decreased by 23 mm Hg (95% confidence intervals 21 to 24 mm Hg) at the
      end of dialysis with respect to the pre-dialysis values. Treatment B reduced this
      intradialytic decrease (P = 0.001) with a maximum effect at the third hour of
      dialysis (4.4 mm Hg, 95% confidence intervals 1.9 to 6.9 mm Hg, 23% less than
      during treatment A, P 0.0005) without any period or carry-over effect (P = 0.53
      and 0.08, respectively). There was no treatment effect on intradialytic diastolic
      blood pressure (P = 0.291). In conclusion, intradialytic cardiovascular stability
      was significantly improved by matching the interdialytic sodium load with
      intradialytic sodium removal using on-line conductivity ultrafiltrate kinetic
      modeling as an alternative to sodium kinetic modeling. Although highly
      significant, this effect was clinically not very large. By applying this
      conductivity kinetic model to patients with a more variable sodium intake from
      one session to another, a greater benefit can be expected.

PMID- 9551418
TI  - Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the
      treatment of infusion pain.
AB  - A randomized, double-blind, cross-over study was undertaken to determine the
      effects of novel bicarbonate (38 mM) and bicarbonate (25 mM)/lactate (15 mM)
      containing peritoneal dialysis (PD) solutions on infusion pain in patients who
      experienced inflow pain with conventional lactate (40 mM) solution. Pain was
      assessed using a verbal rating scale and the validated McGill Pain Questionnaire
      (MPQ). Eighteen patients were recruited to the study. Both novel solutions
      resulted in highly statistically significant reductions in inflow pain compared
      to the control lactate solution, as assessed with both the verbal rating scale
      and the MPQ. For all pain variables assessed, the bicarbonate/lactate solution
      was more effective than the bicarbonate solution in alleviating pain. In
      conclusion, both solutions reduced the infusion pain experienced with control
      solution, but the bicarbonate/lactate solution appears to be the most effective.
      In contrast to the most widespread current treatment, which is the manual
      injection of sodium bicarbonate, the bicarbonate/lactate solution does not have
      the associated increased risk of peritonitis.

PMID- 9551419
TI  - Hemodialysis and L-arginine, but not D-arginine, correct renal failure-associated
      endothelial dysfunction.
AB  - In end-stage renal failure (ESRF) symptomatic hemodialysis-related hypotension
      may prevent effective provision of renal replacement therapy. Endogenous
      inhibitors of nitric oxide synthase accumulate in ESRF and are cleared by
      dialysis. We, therefore, hypothesised that removal of these inhibitors by
      hemodialysis would increase endothelial nitric oxide generation and promote
      venodilation. In vivo responses of norepinephrine preconstricted dorsal hand
      veins to locally active doses of acetylcholine (an activator of nitric oxide
      synthase) and glyceryl trinitrate (GTN; a nitric oxide donor) were examined in
      patients undergoing maintenance hemodialysis for ESRF and in healthy age- and sex
      matched controls. Patient studies were undertaken before and after dialysis.
      Studies before dialysis were repeated with co-infusion of either L-arginine or
      its inactive enantiomer D-arginine. Venodilation in response to acetylcholine was
      impaired before, and corrected by, dialysis whereas venodilation to GTN was
      similar before and after dialysis. Venodilation in response to acetylcholine
      before dialysis was restored by co-infusion of L- but not D-arginine. Therefore,
      patients with ESRF undergoing hemodialysis have impaired acetylcholine-mediated
      venodilation consistent with the accumulation in ESRF of functionally important
      inhibitors of nitric oxide synthase that are cleared by dialysis.

PMID- 9551420
TI  - Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular
      geometry in dialysis patients.
AB  - It is well established that nocturnal hypoxemia in sleep apnea causes an
      inversion of the circadian arterial pressure rhythm and triggers nocturnal
      hypertension. Since sleep apnea is very frequent in dialysis patients, we
      hypothesized that nocturnal hypoxemia may be a factor that contributes to alter
      the 24-hour arterial pressure profile in these patients. To test the hypothesis
      32 dialysis patients underwent 24-hour blood pressure (BP) monitoring and
      continuous monitoring of arterial O2 saturation during the night-time.
      Hemodialysis patients were studied during the non-dialysis day. All patients
      underwent an echocardiographic study. Thirteen patients had no episode of
      nocturnal hypoxemia (group I), 7 had at least one episode overnight but less than
      2 episodes/hr (group II) and 12 had > or = 2 episodes/hr (group III). The average
      daytime systolic pressure was similar in the three groups. However, the average
      nocturnal systolic pressure fell in the first group (-2.5 +/- 4.2%) and rose in
      the second (+2.0 +/- 3.6%) and in the third (+3.9 +/- 2.2%) group (one way ANOVA,
      P < 0.005). The relative wall thickness of the left ventricle (RWT) was
      significantly (P < 0.05) higher in group III than in group I, and in the
      aggregate (N = 32) there was an inverse relationship between average nocturnal
      SaO2 and RWT (r = -0.43, P = 0.015). The proportion of patients with concentric
      remodeling or concentric hypertrophy was higher (P = 0.05) in the group with a
      more severe degree of nocturnal hypoxemia (group III, 8 of 12) than in the other
      two groups (group I, 3 of 13; group II, 2 of 7). Nocturnal hypoxemia is
      associated with the "non-dipping" arterial pressure profile in dialysis patients.
      Disturbed respiratory control during the night may represent an important
      cardiovascular risk factor in dialysis patients.

PMID- 9551421
TI  - Are HUS and TTP genetically determined?

PMID- 9551422
TI  - Morphogenic cues that modulate podocyte growth.

PMID- 9551423
TI  - A novel "bimodal" use of icodextrin peritoneal dialysis solutions.

PMID- 9551424
TI  - Combined kidney-pancreas transplantation.

PMID- 9551425
TI  - Cellular/molecular control of renal Na/Pi-cotransport.
AB  - A type II Na/Pi-cotransporter located in the brush border membrane is the rate
      limiting and physiologically regulated step in proximal tubular phosphate (Pi)
      reabsorption. In states of altered Pi-reabsorption [for example, in response to
      parathyroid hormone (PTH) and to altered dietary intake of Pi or as a consequence
      of genetic abnormalities], brush border expression of the type II Na/Pi
      cotransporter is accordingly modified. PTH initiates a regulatory cascade leading
      to membrane retrieval, followed by lysosomal degradation of this transporter;
      recovery from inhibition requires its de novo synthesis. Pi-deprivation leads to
      an increased brush border expression of transporters that does not appear to
      require de novo synthesis in the short term. Pi-overload leads to membrane
      retrieval and degradation of transporters. Finally, in animals with genetically
      altered Pi-handling (Hyp; Gy) the brush border membrane expression of the type II
      Na/Pi-cotransporter is also reduced, suggesting that a genetically altered
      protein (such as PEX in Hyp) controls the expression of this transporter.

PMID- 9551426
TI  - P-glycoprotein functions and substrates: possible roles of MDR1 gene in the
      kidney.
AB  - There is a renewed attention on the multidrug resistance genes and their
      products, P-glycoproteins, since recent molecular and functional studies revealed
      unexpected functions in normal tissues. There are two types of human P
      glycoprotein: Type I, encoded by the MDR1 gene, present in excretory organs and
      in non-polarized cells; and Type II, encoded by MDR2, present in the canalicular
      membrane of hepatocytes. MDR1 Pgp transports xenobiotics, peptides, steroids, and
      phospholipids, and is also a regulator of swelling-activated chloride channels.
      MDR2 Pgp is exclusively a phosphatidylcholine translocase. In the kidney, the
      MDR1 gene and protein are expressed in mesangial, proximal tubule, thick loop of
      Henle, and collecting duct cells. In mesangial and proximal tubule cells Pgp
      transports xenobiotics. Concomitant exposure of kidney cells to two Pgp
      substrates results in increased cell toxicity. Extracts from supernatants of
      mesangial cell cultures inhibit Pgp-mediated transport, suggesting that a
      mesangial-cell metabolite could be a substrate of Pgp. Active vitamin D3 and
      platelet activating factor inhibit Pgp transport and are possible endogenous
      substrates in proximal tubule and mesangial cells, respectively. Pgp could be
      also a regulator of swelling-activated chloride channels present in the kidney.

PMID- 9551427
TI  - Autocrine/paracrine control of renal phosphate transport.

PMID- 9551428
TI  - Properties and regulation of medullary thick limb basolateral Cl- channels.

PMID- 9551429
TI  - Transducing pathways involved in the control of NaCl reabsorption in the thick
      ascending limb of Henle's loop.
AB  - The thick ascending limb of Henle's loop (TAL) is involved in the urinary
      dilution/concentration process by actively reabsorbing NaCl through a complex
      mechanism. Some years ago, compelling evidence was provided that cAMP stimulates
      NaCl reabsorption through the activation of adenylyl cyclase by several hormones
      other than antidiuretic hormone (ADH). Synthesis of cyclic AMP is inhibited by
      prostaglandin E2 (PGE2) and arachidonic acid per se, via the pertussis toxin
      sensitive protein Gi activation. Cyclic GMP cascade down-regulates NaCl
      reabsorption, through activation of both guanylyl cyclase receptors (by ANF and
      urodilatin), and soluble guanylyl cyclase (by nitric oxide, NO). In TAL, NO is
      produced by the cytokine-inducible form of NO synthase, but not by the
      constitutive one. Agonists known to activate protein kinase C (PKC) in TAL elicit
      opposite effects on NaCl reabsorption. Five PKC isoforms belonging to the
      conventional, novel, and atypical enzyme subclasses have been recently defined in
      TAL and might differently regulate NaCl flux. Increments in intracellular calcium
      ([Ca2+]i) inhibit NaCl reabsorption via three pathways: (i) a possible direct
      effect on ion channels, (ii) a PLA2-mediated production of arachidonic acid
      derivatives (20-HETE), and (iii) inhibition of the ADH-induced cAMP accumulation.
      This last effect results from activation of phosphodiesterase (common to the
      agents that increase [Ca2+]i), and inhibition of adenylyl cyclase (only elicited
      by Ca2+c). Finally, the apical localization of some agonists effects is
      documented.

PMID- 9551430
TI  - H+ and HCO3- transporters in the medullary thick ascending limb of the kidney:
      molecular mechanisms, function and regulation.
AB  - The H+ and HCO3- transporters present in the medullary thick ascending limb
      (MTAL) of the kidney are involved in several functions, such as transepithelial
      transport, defense of cell pH and cell volume. Apical H+ secretion occurs via the
      NHE-3 and NHE-2 isoforms of the Na+/H+ exchanger, and H(+)-ATPase. The apical
      Na+/H+ exchanger is responsible for most of the apical step of transepithelial
      HCO3- absorption and is unresponsive to cell acidification under isosmotic
      conditions. Basolateral HCO3- efflux mechanisms may occur via the Cl-/HCO3-
      exchanger and via the cotransporters K+/HCO3- (in the rat) and Na-3HCO3- (in the
      mouse). However, the role of each transporter in transepithelial HCO3- absorption
      is currently unknown. Inhibition of the basolateral Na+/H+ exchanger (NHE-1)
      paradoxically inhibits the apical Na+/H+ exchanger. This cross talk is
      independent of cell pH and may involve variations in cell volume. Arginine
      vasopressin (AVP) and hyperosmolality induce a differential regulation of
      basolateral NHE-1 and the apical Na+/H+ exchanger. They stimulate the basolateral
      NHE-1, and the resulting cell alkalinization probably stimulates the pHi
      sensitive AE2, which restores cell volume by cellular uptake of NaCl. They also
      inhibit the apical Na+/H+ exchanger, which reduces net HCO3- absorption and thus
      may prevent interstitial fluid alkalinization. Chronic metabolic acidosis
      markedly increases HCO3- absorptive capacity of MTAL, by stimulating at least the
      synthesis of apical NHE-3 protein, as in the proximal tubule. Conversely, chronic
      metabolic alkalosis reduces the apical NHE-3 transport activity by decreasing the
      synthesis of NHE-3 protein. The paradoxical increase in HCO3- absorptive capacity
      of MTAL observed in the model of chronic NaHCO3-load alkalosis should be due to
      other factors overcoming the inhibitory effect of alkalosis on NHE-3.

PMID- 9551431
TI  - Atomic force microscopy of renal cells: limits and prospects.
AB  - In this brief review, we present three-dimensional images of living Madin-Darby
      canine kidney (MDCK) cells and CV-1 cells that illustrate the possibilities and
      limits in the use of atomic force microscopy (AFM) for studying the topography of
      the cell surfaces and of isolated biological membranes. We show that microvilli
      can be imaged at the surface of living epithelial cells. However, when these
      microvilli are abundant and close to each other, the geometry of the AFM tip only
      allows an access to the upper part of the structures and precludes nanometer
      range imaging of the cell surface. Such a nanometer range imaging was obtained
      with other cell types like CV-1 cells and with isolated biological membranes. It
      reveals that protruding particles 5 to 60 nm xy size, likely corresponding to
      membranes proteins, occupy most of the membrane surface. These images indicate
      that the AFM already gives an access to the cell surface structure at the
      mesoscopic scale, which constitutes a major step for the understanding of the
      structure-function relationships in membranes. Perspectives for a further step,
      the imaging at molecular resolution of membranes, are discussed.

PMID- 9551432
TI  - Regulation of sodium transport by steroid hormones.
AB  - The main mechanisms involved in the regulation of sodium transport by steroid
      hormones are briefly reviewed. The respective roles of the apical epithelial
      sodium channel, which is likely to be the limitant step of steroid-regulated
      transepithelial sodium transport, and Na,K-ATPase are described. Regulation of
      these ion transporting proteins by aldosterone and glucocorticoid hormones,
      probably via a two step mechanism (rapid activation of channels or pumps by
      unknown regulators, and modulation of the transcription/translation rate of these
      transporters), is discussed. The mechanisms of mineralocorticoid selectivity,
      that is, the integrated process allowing a specific action of aldosterone, in
      spite of high concentrations of glucocorticoids that crossbind with aldosterone
      to the mineralocorticoid receptor (MR), are explained, as is the role of the
      enzyme 11 beta-hydroxysteroid dehydrogenase and the differential interactions of
      MR with steroid ligands and hormone responsive elements of DNA. Finally,
      synergism between aldosterone and antidiuretic hormone for the stimulation of
      sodium transport is evoked.

PMID- 9551434
TI  - Nitric oxide/endothelin balance after nephron reduction.
AB  - Nitric oxide (NO), an L-arginine derivative, is implicated in neuronal
      transmission, immune response and vasodilation, besides acting as a platelet
      function modulator. A number of recent studies in the experimental model of renal
      mass reduction (RMR) in rats have proposed the hypothesis that abnormalities of
      the NO synthetic pathway could have a key role in mediating the complex
      hemodynamic and hemostatic disorders associated with the progression of renal
      disease. Thus, renal NO generation is lower than normal in rats with RMR seven
      days after surgery, and progressively worsens with time in close correlation with
      signs of renal injury. This abnormality is due to a strong defect of inducible NO
      synthase (iNOS) content in the kidney. In the same model, administration of
      either the NO precursor, L-arginine, or a NO-releasing compound reduces
      proteinuria, slows renal disease progression and prolongs survival. On the other
      hand RMR is associated with a progressive increase of renal synthesis of the
      potent vasoconstrictor peptide, endothelin-1 (ET-1), whose mRNA is expressed in
      excessive amounts in cortical tubules early after surgical ablation. In this
      setting, a marked reduction of NO, in the face of continuous local generation of
      ET-1, may well contribute to intraglomerular capillary hypertension and cell
      proliferation. Actually, administration of a selective ETA receptor antagonist to
      RMR rats reduced abnormal permeability to proteins and prevented renal function
      deterioration. In the same model the ETA receptor antagonist also corrected the
      impaired renal NO synthesis, suggesting that excessive ET-1 bioactivity might
      also be responsible for the progressive reduction of renal NO. In keeping with
      this possibility are recent in vitro data that ET-1 inhibits iNOS transcription,
      a process mediated by interaction of the peptide with subtype A receptors. Nitric
      oxide and ET-1 have profound and opposite effects on glomerular and tubular
      function. Thus, abnormalities of renal NO and ET-1 synthetic pathways, as
      documented in the RMR model, likely have major and complementary roles in
      promoting alteration in renal hemodynamics and functions in progressive
      nephropathies.

PMID- 9551433
TI  - Role of aquaporin-2 water channels in urinary concentration and dilution defects.

PMID- 9551435
TI  - Early molecular mechanisms in the progression of renal failure: role of growth
      factors and protooncogenes.

PMID- 9551436
TI  - Progressive renal disease: the chronic hypoxia hypothesis.

PMID- 9551437
TI  - Sodium transport in alveolar epithelial cells: modulation by O2 tension.

PMID- 9551438
TI  - Role of distal airspace epithelium for resolving alveolar edema.

PMID- 9551439
TI  - Inflammatory role of alveolar epithelial cells.

PMID- 9551440
TI  - Ion transports in the middle ear epithelium.
AB  - Ion transports in the middle ear epithelium have been recently characterized.
      Experimental data using cell culture have found the existence of a sodium
      transepithelial transport that drives a water flow. This is thought to play a key
      role in the maintain of air-filled and fluid-free cavities. Impairment of this
      process is involved in the pathogenesis of secretory otitis media, which is the
      main cause of acquired hearing loss. Several modulations of this transport have
      been evidenced: (i) reactive oxygen species induced an endogenous synthesis of
      prostaglandin E2 (PGE2), which in turn increased the cAMP level and modulated ion
      transport rate; (ii) steroids increased the expression of the alpha subunit
      sodium channel mRNA, which changes paralleled the modulation of ion transport in
      the middle ear epithelium; (iii) moderate hypoxia selectively and reversibly
      decreased the rate of sodium transport, as a result of a parallel decrease in
      alpha epithelial sodium channel subunit mRNA level. These modulations may explain
      the course of middle ear pathology. However, the development of an in vivo model
      has become mandatory to assess the relevance of these data in the pathophysiology
      of the middle ear.

PMID- 9551441
TI  - Mechanisms of endolymph secretion.
AB  - In the inner ear, the membranous labyrinth, a tight heterogeneous sensory
      epithelium, separates two compartments that are filled with fluids of completely
      different composition. The lumen of the membranous labyrinth is filled with
      endolymph, a K-rich, positively polarized fluid, whereas the surrounding spaces
      are filled with perilymph, with a composition similar to an usual extracellular
      fluid. The inner ear fluids play a major role in the cochlear and vestibular
      physiology by the transmission of the mechanical stimulus to the hair cells, on
      the one hand, and by the transduction of this signal to a nerve potential, on the
      other hand. Numerous studies have been performed in order to know the chemical
      and physical characteristics of the inner ear fluids. A high, positive
      transepithelial potential has been evidenced in the cochlea together with a high
      K concentration and a low Na concentration. During the last years, the
      composition of the inner ear fluids, the origins of endolymph and perilymph, and
      the cellular mechanisms involved in the secretion of these fluids have been a
      great part elucidated. The present paper is a review of the contribution of the
      lab to the understanding of the physiology of the inner ear.

PMID- 9551442
TI  - Cell and molecular basis of hearing.
AB  - The mammalian auditory organ is a specialized sensory epithelium capable of
      detecting subnanometer movements produced by sound and transducing them into
      electrical signals. It is a dual system consisting of two types of sensory cells:
      the inner hair cells, which provide afferent input to the central nervous system,
      and the outer hair cells, which provide frequency resolution and signal
      amplification. The critical element in mechano-reception is the hair bundle, a
      cluster of stereocilia located in the apical end of the sensory cells. Mechanical
      stimulation causes deflection of ciliary bundles that leads to the opening or
      closing of transduction channels located in the apical part of the plasma
      membrane of the stereocilia. The current concept of auditory function requires an
      active process of signal amplification within the cochlea. It is generally
      believed that outer hair cells, functioning as both sensor and motor elements,
      are responsible for this amplification process. The motor function consists of
      changes in cell length produced by the concerted action of a large number of
      independent molecular motors distributed along the length of the outer hair cell
      lateral plasma membrane. Although experimental evidence suggests its association
      with conformational changes in transmembrane proteins, the exact nature of the
      outer hair cell force generation mechanism on a molecular level is still unknown.

PMID- 9551444
TI  - [Gentle medicine, harmless medicine?].

PMID- 9551443
TI  - [Presidency of the Society of Nephrology: passing the baton from France to
      Switzerland].

PMID- 9551445
TI  - [Drug-induced glomerulopathies].

PMID- 9551446
TI  - [Use of insulin-like growth factor-I (IGF-I) in the treatment of acute renal
      insufficiency].
AB  - Despite numerous progresses, including extracorporeal epuration, acute renal
      failure (ARF) remains associated with a high level of mortality and morbidity,
      particularly in intensive care unit. Experimental research on different acute
      renal failure models has clearly shown that growth factors and particularly
      Insulin-like Growth Factor I (IGF-I) can reduce renal injury, improve renal
      recovery and even reduce mortality. IGF-I, that is locally produced in injured
      renal tubules, promotes the proliferation and differentiation of new tubular
      cells. Moreover, IGF-I carriers (IGFBPs) and IGF-I receptor are altered in ARF
      and modify the growth factor bioactivity. To date, only two clinical trials
      studied IGF-I treatment in the ARF condition. Other studies are required to
      demonstrate a role for IGF-I in treating or preventing acute renal failure.

PMID- 9551447
TI  - [End-stage renal insufficiency associated with Chinese herbal consumption in
      France].
AB  - In May 1994 in Toulouse, there were two cases of end-stage renal failure (ESRF)
      related to Chinese herbs similar to those incriminated in the case series
      reported in Belgium in 1992-93, they led to an epidemiologic investigation aimed
      at evaluating the risk linked to these plants in France. Studies carried out by
      the Pharmacy Inspection showed that powders labelled Stephania Tetrandra, but
      consisting instead of Aristolochia Fangji and containing aristolochic acid, were
      sold in France between 1989 and May 1994. A systematic attempt to ascertain cases
      of ESRF associated with ingesting Chinese herbs was carried out by analysing data
      from the ERA-EDTA Registry of ESRF as well as from the French adverse drug
      reaction monitoring system. Registry data showed no significant increase over
      previous years in the number of new ESRF cases caused by tubulo-interstitial
      nephritis (TIN) between 1990 and 1993. In eight regions of France, the files of
      85 ESRF cases were examined, and all patients whose nephropathy began after 1989
      were interviewed using a very detailed questionnaire. No association with Chinese
      herb use was found in any of these cases. In 1996, two new ESRF cases were
      reported in Nice; the regional adverse drug reaction monitoring center considered
      the relationship with Aristolochia Fangji to be as possible (I2) for one case and
      dubious (I1) for the other. Despite a lack of sensitivity of the methods used to
      detect cases, it seems clear that no phenomenon as extensive as that observed in
      Belgium occurred in France, although the same drugs prescribed at the same doses
      have been widely distributed in our country. A possible explantation for the
      difference in the number of cases in Belgium and France is that of an
      unrecognised factor, promoting the toxicity of aristolochic acid or peculiar to
      the Belgian clinic and causative. The precautionary principle led the authorities
      to ban Stephania Tetrandra and Aristolochia Fangji from the market permanently.

PMID- 9551448
TI  - [Acute renal insufficiency caused by Amanita proxima poisoning: experience of the
      Poison Center of Marseille].
AB  - In southern France, some Amanita species are usually eaten like Amanita ovoidea
      (Quelet, 1872) which is a common white mushroom. In same areas, a similar and
      less common fungus can be encountered: Amanita proxima (Dumee, 1916). The first
      published cases of Amanita proxima poisonings with acute renal failure have been
      reported in 1994 by a medical team from Montpellier. A second article was
      published in 1995 by physicians from Marseille. In order to evaluate the
      importance of the confusion between the 2 species, we looked after these mushroom
      poisonings collected by the Poison Centre of Marseille. We found 31 cases
      concerning 53 patients. We observed the first intoxication in 1968. Poisonings
      took place in the south of Provence. Ingestions are in 26 cases (83% of the 31
      cases) due to the confusion with Amanita ovoidea. The average delay between the
      meal and the first signs was 13 hours and 12 minutes. All patients had gastro
      intestinal symptoms, and for 14 of them, oliguria or anuria appeared in a few
      days after ingestion. 11 patients needed temporary dialysis, and for 10 of them,
      moderate hepatic cytolysis was observed. The severity of symptoms seems to be
      dose-dependent: we collected cases in the same family with no signs after just
      tasting the meal, digestive symptoms only when patients at more, and renal
      failure for the hungry people.

PMID- 9551450
TI  - [Arteriovenous fistula. Apropos of a local experience in Morocco].
AB  - During eleven years (1983-1994), 684 arteriovenous fistulas (AVF) were realized
      for 422 patients. The mean follow-up was 39 months. The most frequent AVF was
      Cimino and Brescia and the most frequent seat was radial. The failure rate in the
      immediate post-operative period was 10% and 8% after 48 hours. The permeability
      of the AVF was 59%, 51% and 42% at 1, 2 and 3 years. The late complications were
      thrombosis (28%), stenosis (15%) and false aneurysm (11%). In spite of recruiting
      patients with chronic renal failure and deficiency in hospital basic equipment,
      this experience permit us to start and then, to improve the activity of making
      AVF and to be able to pick-up patients with chronic renal failure.

PMID- 9551451
TI  - [Vaccination against hepatitis B in a hemodialysis center].

PMID- 9551449
TI  - [Extracapillary glomerulonephritis secondary to D-penicillamine. Apropos of 1
      case and review of the literature].
AB  - Extracapillary glomerulonephritis was diagnosed in a 51-year-old woman after 11
      months of D-Penicillamine treatment given for systemic sclerosis. Antineutrophil
      cytoplasmic antibodies specific for myeloperoxydase were detected. Penicillamine
      was stopped and the patient was treated with plasma exchanges, cyclophosphamide
      and corticosteroids. The renal function progressively deteriorated leading to end
      stage requiring dialysis. Previous reports of extracapillary glomerulonephritis
      after D-penicillamine are analysed. Several cases with alveolar haemorrhage are
      consistent with the diagnosis of microscopic polyangiitis.

PMID- 9551452
TI  - [Johann Jakob Wepfer's book on apoplexy (1658). Critical comments on a classic in
      neurology].
AB  - The Swiss physician Johann Jakob Wepfer has been hailed as the author of the
      "classic" modern treatise on apoplexy (1658). His name is known because he
      demonstrated that apoplexy resulted from brain hemorrhage or occlusive diseases
      of the vessels. A re-examination of the original text, however, reveals
      surprising evidence that essential parts of Wepfer's book have been neglected so
      far. These chapters demonstrate that Wepfer's medical thinking is deeply rooted
      in pre-modern concepts, e.g. Galenic theories of brain function and iatrochemical
      concepts of disease. A re-evaluation of the non-modern elements of Wepfer's
      treatise leads to a better understanding of the whole text.

PMID- 9551453
TI  - [The persecution of German neuropathologists. 1933-1939].
AB  - The paper reminds of the many psychiatrists, neurologists, and pathologists
      connected with scientific work in neuropathology who were expelled from Germany
      between 1933 and 1939 because of defamation by the Nuremberg Laws or because of
      their political opposition. Many of these colleagues saw their only way out as
      suicide. Short biographies give an orientation about the destiny of the expelled
      physicians in their host countries. The effort made after 1945 to give these
      emigrated colleagues again an adequate position in Germany have not been very
      intensive.

PMID- 9551454
TI  - [Epilepsy in the elderly].
AB  - The new occurrence of epileptic disorders increases continuously above the age of
      60 years. The most frequent etiology of epilepsy in the elderly is vascular (32
      54%). Tumors are the cause of epilepsy in the elderly in 11 to 33 per cent of
      cases, with a peak around the age of 60. The etiology of about one third of the
      cases of epilepsy newly diagnosed in old age cannot be clarified. The risks of
      inducing epileptic disorders are: after cerebral ischemia 4-9%, intracerebral
      hemorrhage 3%, and subarachnoidal hemorrhage 4-12%. It is important to recognize
      confusional states, for they may be symptoms of a psychomotor status or a
      prolonged postical phase. Occasional seizures occur more often in the elderly.
      Due to altered pharmacokinetics and problems of compliance in old age, the
      titration period of antiepileptic drugs should be planned with particular care
      and patients given simple drug regimens.

PMID- 9551455
TI  - [Semiologic classification of epileptic seizures].
AB  - Recent advances in epileptology and epilepsy surgery require revision of the
      currently used International Classification of Epileptic Seizures, which was
      published 1981. We present a classification of epileptic seizures which is based
      purely on the clinical seizure semiology. The advantages of a semiological
      seizure classification are stressed.

PMID- 9551456
TI  - [Juvenile myoclonic epilepsy (Janz syndrome). A well-known epilepsy syndrome?].
AB  - Juvenile myoclonic epilepsy (JME) was described electroclinically by Janz and
      Christian in 1957 and consists of myoclonic jerks in varying combination with the
      absence of seizures and generalized tonic-clonic seizures, a typical circadian
      distribution on awakening, sleep deprivation, alcohol consumption and flickering
      stimuli as characteristic precipitating factors, typical EEG abnormalities with
      generalized epileptiform discharges, normal physical and neuroradiological
      findings, and often a family history of epilepsy. Although the misdiagnosis of
      this well-classified and easily treatable syndrome is supposed to occur rarely in
      Germany, we retrospectively investigated how often the wrong initial
      classification had been made among patients who were finally treated in our
      outpatient epilepsy unit. Between 1993 and 1995, 30 patients with a typical JME
      like symptom constellation were identified who had been misdiagnosed initially.
      In all patients, localization-related epilepsy had been classified, although
      regional EEG abnormalities were rare (n = 5). All patients reported the typical
      circadian distribution, abnormal neuroradiological findings were absent, and
      typical EEG abnormalities were present in all cases. Under treatment with
      appropriate antiepileptic drugs 97% of the patients became almost completely
      seizure-free. Even 40 years after the first description of the syndrome, JME is
      an underdiagnosed illness. The generally positive course underlines the
      importance of its correct identification.

PMID- 9551457
TI  - [Transcranial Doppler exercise test in patients with chronic tension headache].
AB  - In the etiopathology of tension type headache, vascular and autonomic disorders
      are discussed. Fifteen patients with chronic tension type headache according to
      the criteria of the IHS were investigated using the TCD-ergometer-test--a method
      used to evaluate the myogenic mechanism of cerebrovascular autoregulation--and
      the results were compared with the findings in fifteen healthy control subjects.
      The patients' Mean Flow Velocity (TAVmean) and Resistance Index (RI) at rest and
      after exercise were significantly decreased (p < 0.05). During exercise they
      normalized. The patients' endtidal pCO2 at rest and during exercise was
      significantly lower than the corresponding values of the control group (p <
      0.05). Regarding blood pressure elevation and heart rate increase during exercise
      both groups did not differ significantly (p > 0.05). These findings suggest that
      patients with tension type headache have a diminished vascular tone in the
      cerebral vessels at rest which is normalised during exercise. The reduced
      endtidal pCO2 is considered as a physiological response to increase vascular tone
      via metabolic mechanism of cerebrovascular autoregulation. In conclusion it is
      suggested that therapeutic procedures which activate sympathetic autonomic
      nervous function to train cerebral vessels should be more carefully considered.

PMID- 9551458
TI  - [Follow-up of myasthenia gravis. Results of a longitudinal study of the
      significance of psychosocial predictors].
AB  - Forty-two patients suffering from myasthenia gravis were examined in a
      longitudinal study design. The aim of the study was to investigate possible
      psychosocial predictors for the course of the disease. At the time of the first
      examination (T1) the diagnosis myasthenia gravis had been established for no
      longer than 1 year. Two further examinations were done at 6 months (T2) and 18
      months (T3) after T1. Methods consisted of a personality questionnaire (FPI), a
      coping questionnaire (FKV), an assessment of neurotic symptoms by interviewers
      (PSKB) and an assessment of the doctor-patient relationship by the attending
      physicians. Two different severity scores (Oosterhuis Index, Myasthenia Score)
      served as criteria for the course of the disease. There was no connection between
      the course of myasthenia gravis and neurotic symptoms like anxiety or depression
      and the quality of the doctor-patient relationship (both assessed at T1). Also
      demographic data were independent from the development of severity scores. The
      personality factor extraversion was associated with a positive course of the
      disease, aggressiveness and worrying about health with a negative one. Among the
      coping behaviors religiousness and looking for sense were associated with a
      favorable course but that was shown only regarding the Oosterhuis Index and not
      the Myasthenia Score. As several T1 personality factors were predictive for the
      severity scores at T3, these results may suggest a causal influence of
      personality factors on the severity of the illness. Whether or not this
      relationship is actually in operation, however, remains ellusive. Further studies
      using an experimental design are needed to strengthen this hypothesis.

PMID- 9551459
TI  - [Effect of cardiac embolism sources on origin of territorial cerebral infarcts].
AB  - BACKGROUND AND PURPOSE: To test the association of cardiac sources of embolism
      with territorial type brain infarcts. METHODS: From a prospective cerebral
      ischemia data base the 106 consecutive patients with territorial type cerebral
      infarcts on computerized tomography were analyzed. The 85 consecutive patients
      with lacunar lesions served as a comparison group. The association of cardiac
      sources of embolism with territorial types infarcts was assessed using univariate
      Chi Square tests and logistic regression models. Cardiac sources of embolism were
      defined as:atrial fibrillation, left cardiac thrombi, valvular vegetations, wall
      motion and valvular abnormalities, left atrial enlargement, open foramen ovale,
      septal aneurysm, mitral valve prolaps, and aortic arch atherothrombosis (all
      findings--except for atrial fibrillation--assessed by echocardiography). RESULTS:
      Atrial fibrillation was significantly associated with territorial type infarcts
      (odds ratio 2.2, 95% confidence interval 1.01-4.8). This effect was independent
      of additional cardiac diseases, other cardiac abnormalities, carotid artery
      stenosis, and patient age. Most likely due to the small sample size, left cardiac
      thrombi only showed a non-significant trend towards an association with
      territorial infarcts (odds ratio 3.0, 95% confidence interval 0.7-12.3). The rate
      of all other cardiac findings did not differ significantly between the comparison
      groups. CONCLUSION: Atrial fibrillation and cardiac thrombi showed an association
      with territorial type infarcts. Other so-called cardiac sources of embolism-
      except for mechanical valves and bacterial endocarditis which were not
      represented in our sample--revealed no clinically relevant association with
      embolic brain infarct pattern.

PMID- 9551460
TI  - [Asystolic seizures].
AB  - Epileptic seizures may alter autonomic functions. This is especially the case
      with complex focal seizures (of temporal lobe origin) and grand mal. Most
      frequently, such seizures cause ictal tachycardia, sometimes tachypnea, probably
      caused by the propagation of epileptic discharges to autonomic cerebral
      structures. Ictal bradycardia and asystole are rare phenomena. However, they may
      be life threatening. Their differentiation from primary cardiac arrest is
      possible by the use of ictal EEG and ECG registration. Postictal serum prolactin
      measurement does not differentiate syncope from seizure. However, a postictal
      increase of creatine kinase is only measured after epileptic seizures and not
      after syncope. Treatment of such epileptic seizures includes an optimization of
      anticonvulsant drug therapy and the implantation of a cardiac demand stimulator.
      There is growing evidence that ictal asystole is a cofactor in sudden unexplained
      death in epileptic patients.

PMID- 9551461
TI  - [Successful induction of tolerance in an epilepsy patient with phenobarbital
      allergy].
AB  - We report on a 32-year-old female patient who had had a history of complex
      partial seizures since the age of 14. Phenobarbital was the most effective
      anticonvulsant drug in this patient. However, the drug treatment was complicated
      by a phenobarbital-induced exanthematous eruption. Reintroduction of the
      phenobarbital some years later resulted in a skin rash again; therefore,
      treatment with this substance had to be discontinued a second time. Because of
      the satisfactory antiepileptic efficacy, phenobarbital was introduced a third
      time using a desensitization procedure with increased oral doses, starting with a
      dose of 1 mg. After a daily dose of 90 mg phenobarbital, on day 6 an
      exanthematous eruption appeared. The exanthem disappeared parallel to a dose
      reduction of phenobarbital and with a gradually increasing dosage up to a
      maintenance dose of 200 mg. Tolerance to the allergic effect of phenobarbital was
      preserved and the seizure frequency was significantly reduced by phenobarbital
      monotherapy with a daily dose of 200-175 mg.

PMID- 9551462
TI  - [Subacute encephalopathy with epileptic seizures in a patient with chronic
      alcoholism (SESA syndrome)].
AB  - Subacute encephalopathy with seizures in alcoholics (SESA syndrome) is a rare
      disease entity following chronic alcohol ingestion. It is quite distinct from
      alcohol withdrawal syndromes, such as delirium, withdrawal seizures or CNS
      complications of alcohol, such as Wernicke-Korsakow syndrome, central pontine
      myelinolysis or Marchiafava-Bignami disease, and was proposed in 1981 by
      Niedermeyer and coworkers. This syndrome consists of multiple neurological
      deficits, such as hemiparesis or hemianopia, and of recurrent focal and
      generalized seizures associated with prominent EEG features (periodic lateralized
      discharges, PLEDs). A 72-year-old Caucasian male with chronic alcoholism and an
      otherwise unremarkable past medical history was admitted to our hospital because
      of several secondary generalized simple partial seizures. Laboratory
      investigations revealed elevated levels of gamma-glutamyltranspeptidase and of
      mean corpuscular volume. Other laboratory investigations and the CSF examinations
      on three occasions revealed normal values. Cranial computed and magnetic
      resonance tomography showed cerebral microangiopathy and generalized atrophy.
      Despite triple anticonvulsive therapy and an intravenous treatment with acyclovir
      and thiamine, the epileptic seizures persisted. Several EEGs revealed left
      parietooccipital periodic lateralized epileptiform discharges (PLEDs). The
      patient died of an intercurrent pulmonary infection about 3 months after the
      onset of symptoms. The described clinical picture resembles the symptoms of SESA
      syndrome.

PMID- 9551463
TI  - [Day time fatigue in frontal lobe epilepsy with primarily sleep-related seizures.
      A case report].
AB  - We present a 43-year-old patient who has had up to 15 frontal lobe seizures
      nightly for 12 years. The patient had no complaints apart from excessive daytime
      sleepiness. Neurological and psychiatric examination as well as cerebral computed
      tomograph and magnetic resonance imaging were normal. After sleep deprivation an
      interictal electroencephalogram demonstrated a recurrent excess of theta activity
      over the right frontal and frontopolar area. A cerebral PET study showed
      diminished glucose metabolism of the right cingular and frontomesial region. The
      sleep structure was extremely fragmented. There was an excessive reduction of
      slow-wave sleep and REM sleep. Carbamazepine therapy produced complete seizure
      control lasting a few weeks, followed by return of up to 8 seizures per night.
      Vigabatrin as add on therapy diminished the noctural seizures to 1 to 3 per
      night.

PMID- 9551464
TI  - [Acute intermittent porphyria with transient paresis and contracture. Evidence
      for initial myopathic dysfunction?].
AB  - A 70-year old man with acute intermittent porphyria had acute transient
      bibrachial paresis with moderate contracture of the involved muscles, which
      showed electrical silence in a conventional electromyographic investigation with
      surface electrodes placed over the contracted muscle belly (filter: 20 Hz-2 Hz,
      amplifier 50 microV). Slow finger movements were still possible and showed
      typical muscle-action potentials. This electroclinical correlation points to
      myopathic localized dysfunction, perhaps similar to rare case reports with
      patients having metabolic myopathy of McArdle's type.

PMID- 9551466
TI  - [Recommendation for organization of special stroke departments (stroke units).
      1997 implementation].
AB  - Stroke units are hospital-based special wards aiming at optimal care by a
      specialized team with an integrated concept for patients with acute strokes.
      Following the initial neurological and neuroradiological evaluation, early
      treatment will be initiated based on the assumed pathophysiology of the stroke.
      Acute management includes monitoring of physiological, parameters, care by
      specialized nurses, and early implementation of physiotherapists, speech therapy
      and occupational therapy. Despite the increased initial costs, the long-term
      burden for the health system is decreased by shorter hospital stay and reduced
      morbidity and disability.

PMID- 9551465
TI  - [Adrenoleukodystrophy and adrenomyeloneuropathy. Clinical biochemical and
      molecular genetic findings].
AB  - Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disease affecting 1 in
      20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy
      (AMN) in adulthood. Recently, the ALD gene has been identified by positional
      cloning. We report three males patients with AMN and a fourth patient with
      juvenile ALD. Biochemical studies showed elevated plasma concentration of
      saturated very-long-chain fatty acids. Genomic DNA of the patients was analysed
      for possible sequence variations in the ALD gene by PCR amplification and single
      strand conformation polymorphism analysis. Three missense mutations (Ser515Phe,
      Glu267Lys and Arg401Trp) and a 9-bp deletion were detected predicting,
      respectively, the replacement and absence of amino acids in the deduced amino
      acid sequence of the ALD protein. In the patients' families, detection of the
      respective mutations allows the identification of carriers of ALD/AMN. Mutational
      screening in ALD families is of practical importance in improving genetic
      counseling.

PMID- 9551467
TI  - [Dynamic cellular response following brain ischemia and reperfusion].
AB  - Since the first documentation of the induction of heat shock protein following
      transient cerebral ischemia, much experimental evidence suggested that all of the
      cellular elements in the central nervous system show dynamic stress responses
      depending on the degree of environmental changes induced by ischemia and
      reperfusion. In this review, first I focused on the importance of the usage of an
      appropriate experimental model for brain ischemia and reperfusion, and I
      presented our work on mouse models of transient global and focal ischemia. Next,
      I reviewed the pathogenic role of microvascular stasis (i.e., secondary ischemia)
      caused by the primary ischemic event and demonstrated the important role of cell
      adhesion molecules through the experiments using ICAM-1 knock-out mouse as a
      model of brain ischemia/reperfusion. Thirdly, I discussed the ischemia-induced
      neuronal cell responses in relation to the apoptosis-like selective neuronal
      death and the induction of adopted stress responses including stress protein
      synthesis and 'ischemic tolerance' phenomenon. A variety of stress proteins
      induced by ischemic stress have been reviewed and a pivotal role of tyrosine
      kinase system in selective neuronal death has been suggested in the gerbil model
      of transient forebrain ischemia. Finally, I showed the important
      pathophysiological roles of glial cells such as astrocytes and oligodendrocytes
      in the cellular cross-talk triggered by an ischemic event. For the development of
      a novel therapeutic agent against ischemic stroke, it is quite important to
      clarify both the negative and positive cellular responses induced by brain
      ischemia/reperfusion.

PMID- 9551468
TI  - [Response of Na+/Ca2+ antiporter to ischemia and glial/neuronal death].
AB  - Brain ischemia produces morphologic and biochemical alterations in astrocytes.
      This mini-review summarizes astrocytic responses to brain ischemia including our
      studies on the neuronal and astrocytic Na(+)-Ca2+ exchanger (NCX). NCX is
      considered to cause Ca2+ efflux (forward mode) or Ca2+ influx (reverse mode),
      depending on the electrochemical gradient of Na+ across the plasma membranes and
      membrane potential. We demonstrated that NCX is present in cultured neurons and
      astrocytes and that there are differences in their properties and distribution
      ratio of the isoforms between neurons and astrocytes. We also found that Ca2+
      depletion followed by reperfusion with Ca(2+)-containing medium caused cell death
      in cultured astrocytes (Ca2+ paradox-like injury), but not in neurons. The study,
      carried out by the use of a specific antisense oligomer, provides direct evidence
      that Ca2+ paradox-like injury is mediated by NCX in the reverse mode. The injury
      was attenuated by inhibitors of the Na(+)-Ca2+ exchanger, heat shock protein and
      the calcineurin inhibitor FK506. In a preliminary experiment, we found that brain
      ischemia decreases the mRNA level of NCX in the hippocampus. Further studies on
      activation and cell injury of astrocytes will contribute to development of new
      drugs that modulate the function of astrocytes.

PMID- 9551469
TI  - [Involvement of calcineurin A alpha and A beta in neuronal death in a gerbil
      model of cerebral ischemia].
AB  - Treatment with FK506, an inhibitor of Ca2+/calmodulin dependent phosphatase
      (calcineurin, CaN), within 1 hr after transient ischemia afforded protection from
      apoptotic death in CA1 pyramidal neurons. To investigate isoform-specific roles
      of CaN in the neuronal cell death, we localized CaN A alpha and CaN A beta in the
      gerbil hippocampus using isoform-specific antibodies. In control gerbils,
      immunoreactions of both isoforms were highly enriched in hippocampal CA1
      pyramidal neurons. Four to seven days after the induced ischemia,
      immunoreactivities of both isoforms were markedly reduced in the CA1 pyramidal
      cell and lacunosum-molecular layers. The CaN A alpha immunoreactivity was
      increased in the CA1 radiatum and oriens layers, whereas that of CaN A beta was
      enhanced in reactive astrocytes in the CA1 region. These findings suggest that
      CaN A alpha is involved in sprouting of afferent fibers in CA1 and that CaN A
      beta is involved in the reaction of astrocytes such as assembly of glial fibril
      acidic protein.

PMID- 9551470
TI  - [The glial endothelin-nitric oxide system in ischemia-related neuronal cell
      death].
AB  - Both endothelin and nitric oxide (NO) have been proposed to act as
      pathophysiological factors in ischemia-related neural damage. This review is
      concerned with the participation of the glial endothelin-NO system in ischemia
      related neuronal cell death. In the rat brain with cerebral apoplexy, endothelin,
      endothelin receptors and NO synthase (NOS) were rich in the glial cells of
      damaged brain areas. The brain subjected to transient forebrain ischemia
      contained astrocytic endothelins and microglial expressions of the ETB-receptor
      and NOS aggregating in the damaged CA1 subfield of the hippocampus at 7 days
      after the ischemia. Astrocytic endothelin, ETB-receptor and NOS became more
      apparent at 28 days after the ischemia, corresponding to a time when neural
      tissue-repair/remodeling after damage occurs, whereas no activities of the
      endothelin-NO system are observed in microglia. In the in vitro experiment,
      endothelin was found to modulate the release of NO from the hippocampal slices
      subjected to transient forebrain ischemia. There may be a cross-talk between the
      endothelin system and NO in the astrocytes and microglia during the process of
      ischemia-related neuronal cell death and neural tissue-remodeling.

PMID- 9551471
TI  - [The involvement of cytokines, chemokines and inducible nitric oxide synthase
      (iNOS) induced by a transient ischemia in neuronal survival/death in rat brain].
AB  - Inflammatory/immunological processes underlie the survival/damage of neurons
      after brain ischemia. In glial cells, cytokines such as IL-1 beta and TNF-alpha
      are produced following ischemic stresses. On the other hand, it is suggested that
      NO/iNOS is involved in neuronal apoptosis. We here review the ischemia-induced
      production of cytokine/iNOS and the neurotrophic/neurotoxic effects. It is not
      clear whether or not the neuronal death after brain ischemia is apoptosis or
      necrosis. Under the condition of transient forebrain ischemia, however, we
      obtained results suggesting apoptosis in the delayed neuronal death of the CA1
      pyramidal neurons. The time course and cellular localization of postischemic iNOS
      expression depend on the properties of the ischemic insult. The iNOS induction is
      detected primarily in astrocytes after the transient forebrain ischemia when the
      neuronal apoptosis is observed. We discuss a variety of cytokines with
      neurotrophic/neurotoxic actions that are produced by ischemia or environmental
      stresses in glial cells. From the neurotoxicological aspect of the neuro-glial
      interaction, we also review recent findings on signalling pathways of the iNOS
      induction in glial cells and the mechanisms of the cytotoxic actions of NO.

PMID- 9551472
TI  - [Lack of evidence that inducible nitric oxide synthase participates in the
      development of ischemic brain damage].
AB  - We have already reported that the concentration of nitric oxide (NO) increases
      during and after cerebral ischemia and a selective inhibitor of neuronal NO
      synthase (nNOS) suppresses this increase and subsequently mitigates brain damage
      in rats. Although the selective inhibition of nNOS is a promising pharmacological
      strategy for the treatment of stroke, the role of inducible NOS (iNOS) remains to
      be clarified. Toward this end, we investigated temporal alterations in iNOS mRNA
      by the RT-PCR method in a rat model of middle cerebral artery (MCA) occlusion. We
      found that iNOS mRNA in the ischemic hemisphere began to increase at 3 hr and
      reached the maximum level at 24 hr of reperfusion following 3 hr of MCA
      occlusion. However, quantitative analysis revealed that no significant difference
      existed between 6 hr or 24 hr reperfusion group and their respective time-matched
      sham operation group. In addition, neither Western blotting nor
      immunocytochemical study disclosed an apparent induction of iNOS at any time
      points examined. Similar results were obtained at 24 hr of permanent MCA
      occlusion. Taken together, these data indicate that iNOS induction during and
      after MCA occlusion may be not a critical event for the development of infarction
      caused by ischemia itself.

PMID- 9551473
TI  - [Transient cerebral ischemia and long-term potentiation in the rat hippocampus].
AB  - Long-term potentiation (LTP) has been widely studied as a form of synaptic
      plasticity that represents a cellular mechanism of learning and memory. Among
      numerous processes and molecules that may be involved in LTP formation, a great
      many of them including neurotrophic and transcription factors have been described
      as those involved in neural death after ischemic insult. Nitric oxide (NO) is a
      molecule that is known to also exert double-edged effects on LTP formation. Here
      we will be describing recent advances with respect to the LTP mechanisms in the
      hippocampal synapses, a critical brain region for learning and memory function.
      In another context, we described our study elucidating the changes in hippocampal
      LTP as a functional response to transient cerebral ischemic insult, from the
      viewpoint of its relevance to NO production. As indices of NO production, nitrite
      and nitrate levels were determined by in vivo microdialysis. It was demonstrated
      that hippocampal LTP deficiency after transient cerebral ischemia was preceded by
      an increase in hippocampal NO production. Direct or indirect inhibition of an
      inducible NO synthase restored ischemia-induced LTP deficiency. These findings
      suggest that NO production, in part via inducible NO synthase, is responsible for
      LTP deficiency after transient cerebral ischemia in the rat hippocampus.

PMID- 9551474
TI  - [A method of measuring eruptive movement of the rat incisor using a non
      contacting displacement detector].
AB  - The axial movements of rat incisors were recorded continuously for over 20 hr.
      The rats were anesthetized with halothane delivered by intratracheal intubation
      using an artificial respirator. A hemostatic clamp was used to immobilize the
      jaw. The displacement detector that detects changes in the electric eddy current
      exhibited high resolution, good linearity and low drift. The average eruption
      rates of the rat incisor were estimated to be 406 and 516 microns/ 24 hr at 34
      and 37 degrees C of the rectal temperature, respectively. The values were within
      the normal range. We also measured the force needed to restrain eruptive movement
      of the rat incisor using the same apparatus combined with a load cell. The
      maximum pushing force was estimated to be 9 mN or 29 mmHg (converted value) on
      average. Then the effects of adrenaline on axial movement of the incisor and
      arterial blood pressure were examined. Adrenaline caused a rapid extrusive tooth
      movement with a nearly simultaneous increase in the blood pressure, followed by a
      marked intrusive tooth movement and a decrease in blood pressure. These results
      support the view that the systemic arterial blood pressure and vasculature in the
      tooth socket play important roles to determine the position of teeth. We assume
      that our method would be useful to clarify the precise relationship between tooth
      displacement and vascular change in the tooth socket.

PMID- 9551475
TI  - Comparison of ELISA and HI for detection of antibodies against Wesselsbron
      disease virus.
AB  - A two-graph Receiver Operating Characteristic analysis was done to determine the
      optimal cut-off value of an indirect enzyme-linked immunosorbent assay (ELISA)
      for detection of antibodies to Wesselsbron disease (WSL) virus. When ELISA and
      haemagglutination-inhibition (HI) results of WSL-positive and WSL-negative
      control sheep sera were compared, the sensitivity of ELISA was 97.9% and that of
      HI, 87.5%, while the specificity of ELISA and HI were 95.7% and 100%,
      respectively. The ELISA's superior sensitivity was confirmed by the results of
      the two assays performed on a simulated range of low-positive sera, which showed
      that the ELISA was able to detect WSL-antibody levels at least ten times lower
      than those the HI could. The ELISA was also less cross-reactive than the HI to
      guinea-pig antisera against nine flaviviruses relevant to southern Africa. The
      combination of the ELISA's ability to test untreated sera in single dilution and
      its superior sensitivity and lower cross-reactivity as compared to that of the
      traditional HI, makes it the assay of choice for automation and large-scale
      screening of animals for antibodies to WSL virus.

PMID- 9551476
TI  - The control of Glossina morsitans morsitans (Diptera: Glossinidae) in a settled
      area in Petauke District (Eastern Province, Zambia) using odour-baited targets.
AB  - A trial to control G. m. morsitans with the use of 980 odour-baited, insecticide
      impregnated targets was conducted in a 300 km2 area in the Eastern Province of
      Zambia between 1989 and 1991. The area is highly cultivated and cattle density is
      high (about 8 cattle/km2). Targets were deployed along roads and tracks.
      Deployment was restricted to suitable tsetse habitat. The effect of the targets
      on the tsetse population and on the transmission of tsetse-transmitted
      trypanosomosis was monitored by means of man-walked fly rounds and sentinel
      herds, respectively. The apparent density of tsetse in the trial area and in
      adjacent areas, declined rapidly after targets had been deployed. Trypanosomosis
      incidence in the trial area decreased significantly but did not completely
      disappear. Results from the trial show that odour-baited targets are effective in
      controlling Glossina m. morsitans in highly cultivated areas even when deployment
      is restricted to suitable tsetse habitat. It is concluded that tsetse control
      operations should be chosen such that either the invasion pressure is low from
      adjacent areas, or the size of the area is big enough, so that a central
      challenge-free area can be created.

PMID- 9551477
TI  - Seasonal abundance and parity of stock-associated Culicoides species (Diptera:
      Ceratopogonidae) in different climatic regions in southern Africa in relation to
      their viral vector potential.
AB  - Seasonal abundance and parity in Culicoides populations, in the vicinity of
      livestock, were determined at seven sites in five different climatic regions with
      220 V down-draught blacklight-traps. In 418 collections made between October 1983
      and December 1986, a total of 2,134,171 Culicoides, of which 342,571 were
      identified to species level and sexed, were collected; 267 of these collections
      (182,321 Culicoides) were graded for parity. In the frost-free summer rainfall
      area, Culicoides were collected in large numbers in light-traps throughout the
      year; this implies breeding and possible virus transmission throughout the winter
      in certain parts of South Africa. However, where frost occurred, Culicoides
      numbers usually peaked in late summer and dropped sharply after the first frost.
      In the latter areas, small Culicoides collections during winter may be due to low
      winter temperatures and rainfall; low temperatures negatively affect adult
      activity and reduce the rate of development of larvae and pupae; low rainfall
      would lead to a reduction of available larval habitats. Relatively large numbers
      of Culicoides were collected in winter in the temperature frost-free winter
      rainfall area. In each of the four summer rainfall areas, one Culicoides species
      remained dominant throughout the year: at two of these areas this species was C.
      imicola. Other abundant species in some of these summer rainfall areas were C.
      schultzei s.l. and C. zuluensis. In the winter rainfall area, C. zuluensis, C.
      magnus, C. gulbenkiani and C. imicola shared abundance. It was established that
      abdominal pigmentation is an indicator of parity in C. imicola in South Africa.
      With the increase in Culicoides numbers towards the end of summer, there was also
      a rise in the proportion of parous (pigmented) females in most Culicoides
      species, which signifies a higher vector potential for African horsesickness and
      bluetongue towards the end of summer. This coincides with the seasonal occurrence
      of viral diseases transmitted by Culicoides species. Nulliparous (unpigmented)
      females of all Culicoides species were present throughout the year at all sites
      where Culicoides were continuously collected, confirming uninterrupted breeding
      in these areas.

PMID- 9551478
TI  - Predation of livestock ticks by chickens as a tick-control method in a resource
      poor urban environment.
AB  - The possible use of chickens as predators of livestock ticks was studied.
      Chickens were allowed to scavenge for 3 h among tick-infested cattle in a typical
      township backyard during the milking period. Boophilus decoloratus, Hyalomma
      marginatum rufipes, Rhipicephalus evertsi evertsi and Otobius megnini were
      recovered from the crops and gizzards at necropsy. The numbers of ticks ingested
      ranged from 0-128, with an average of 28.81 (+/- 8.42) per chicken. This study
      has confirmed that chickens are natural predators of livestock ticks and that
      chickens can be used as part of an integrated tick control plan in urban cattle
      management systems in resource-poor communities in South Africa.

PMID- 9551479
TI  - Salmonella isolated from crocodiles and other reptiles during the period 1985
      1994 in South Africa.
AB  - Over a 10-year period, 173 isolates of Salmonella were obtained during routine
      isolation from reptiles. Of the 173 isolates, 92 different Salmonella serovars
      were identified. Of them, 61 (66%) belonged to subspecies I, nine to subspecies
      II and 21 to subspecies III (IIIa and IIIb), and one to subspecies IV. The
      majority of isolates were from farmed Nile crocodiles (145), three from wild
      caught African dwarf crocodiles, 11 from captive snakes, 13 from lizards and one
      from a tortoise. The isolates from the tortoise and lizards were subspecies I
      isolates (Zaire and Tsevie, respectively). Of the snakes, nine isolates were
      S.III. The serovars isolated most often from the crocodiles were of subspecies I
      (32 serovars). Eight were from subspecies II, seven from subspecies III and one
      from subspecies IV. The most frequently identified serovars were Typhimurium
      (seven), Tsevie (six), Duval (six), Schwerin (six), Tinda (six), and Tallahassee
      (six). On two commercial crocodile breeding farms that had experienced ongoing
      problems for about two years, many isolates of Salmonella were made. Some of
      these serovars were isolated more than once, and also months apart. No single
      Salmonella serovar predominated, nor did a single pathological condition. These
      salmonellas were predominantly of subspecies I.

PMID- 9551480
TI  - Parasites of South African wildlife. XV. Helminths of scrub hares, Lepus
      saxatilis in the Kruger National Park.
AB  - A total of 145 scrub hares from three localities in the Kruger National Park were
      examined for helminths: 124 at Skukuza, 15 at Shingwedzi, and three each at
      Pretoriuskop and Pafuri. Trichostrongylus deflexus was the most prevalent and
      most abundant nematode, and was collected from hares from all four localities.
      Trichostrongylus falculatus was present in three localities. Trichostrongylus
      thomasi and Dermatoxys vlakhaasi occurred only at Skukuza in 50 and 23%,
      respectively, of the hares examined. The cestode Mosgovoyia pectinata and the
      nematode genus Impalaia were each recovered from three localities and Cooperia
      hungi from two. There was no apparent seasonal pattern of abundance of the worms,
      and the intensities of infection of male and female hares were similar. With the
      exception of D. vlakhaasi, all the helminths recovered in this study represent
      new records for scrub hares in South Africa.

PMID- 9551481
TI  - The structure of the interstitial tissue of the active and resting avian testis.
AB  - The interstitial tissue of the testis was studied in gonadally active and
      gonadally inactive domestic fowl (Gallus gallus domesticus), guinea-fowl (Numida
      meleagris), duck (Anas platyrhynchos) and Japanese quail (Coturnix coturnix
      japonica). Gonadal inactivity in the fowl was induced by a single subcutaneous
      injection of 50 mg oestradiol benzoate. The structure of this tissue was similar
      in all the birds studied. Lymphatic vessels were mostly thin and meandered
      between the peritubular tissue peripherally and the centrally located blood
      vessels, Leydig cells and macrophages. The basal lamina rested on a closely
      associated homogeneous microfibrillar layer free of collagen fibres. The
      myofibroblast layer was several cells thick, and quite compact. The basal lamina
      of gonadally resting birds was highly irregular, relatively electron-dense,
      contained electron-lucent globules, and sent numerous finger-like processes or
      plicae into the seminiferous epithelium, particularly into the Sertoli cells. The
      Leydig cells were few but typical in structure. In gonadally inactive birds they
      accumulated lipid droplets, dense heterogeneous bodies, probably lysosomes, and
      appeared to degenerate. The avian testicular interstitium is similar to that of
      the human and cat in possessing a multi-layered myofibroblast component, and to
      that of the rodent in possessing a small number of Leydig cells, as well as in
      the location of the lymphatic vessels. Thus the bird combines characteristics of
      the interstitium found variably in mammals.

PMID- 9551483
TI  - Evaluation of a 3 ml heartwater (cowdriosis) infective blood vaccine dose.
AB  - Three milliliters of blood from the present commercially produced heartwater
      infective blood vaccine (Ball3 stock) was experimentally tested in sheep and
      cattle for infectivity and efficacy. Results obtained for this vaccine dose were
      statistically not different from results for the prescribed 5 ml vaccine dose.

PMID- 9551484
TI  - Seroepidemiological survey of sympatric domestic and wild dogs (Lycaon pictus) in
      Tsumkwe District, north-eastern Namibia.
AB  - Disease is a potential threat to many endangered populations and may originate
      from sympatric domestic species. This paper describes a cross-sectional
      serological survey of canine pathogens carried out in domestic (n = 70) and wild
      dogs (Lycoan pictus) (n = 6), in Tsumkwe District, northeastern Namibia. Evidence
      of past exposure to canine distemper virus, canine adenovirus and parainfluenza
      virus was evident in both wild and domestic dogs with this, the first, documented
      exposure of free-living wild dogs to canine distemper. Domestic dogs were also
      exposed to rabies virus, canine parvovirus and coronavirus. There was no pathogen
      to which wild dogs, but not domestic dogs, were exposed. With wild dogs known to
      be susceptible to rabies and canine distemper, these may be the greatest threat
      to this population of wild dogs, although some wild dogs can clearly survive
      infection with canine distemper.

PMID- 9551482
TI  - Toxorhynchites-fluorescent antibody system for the detection of bluetongue virus
      from Culicoides midges (Diptera: Ceratopogonidae).
AB  - A new system, the Toxorhynchites-fluorescent antibody (TFA) test in which the
      larvae of Toxorhynchites splendens mosquitoes were used for the detection of
      bluetongue virus (BTV) from Culicoides midges, was developed. Twenty-seven pools
      of Culicoides midges were collected from bluetongue-prone areas of Tamil Nadu by
      use of the light-trap and suction-trap methods. A suspension of each pool was
      injected intrathoracically into T. splendens IV instar larvae and inoculated onto
      Vero cell monolayers. An indirect fluorescent antibody technique and an
      immunoperoxidase test were used to detect BTV antigen in smears of crushed
      midges, crushed larval head smears after incubation for 7 d at 28 degrees and
      cell monolayers showing cytopathic effects 48 h post inoculation. The suspensions
      were also injected intravenously into embryonated chicken eggs, and the
      characteristic BTV-induced lesion(s), viz. cherry-red appearance of embryos, were
      observed after 48 h. Virus was confirmed by a qualitative neutralization test
      conducted simultaneously in embryonated chicken eggs. A total of seven out of 27
      samples (26%) were positive for the presence of BTV antigen in all the diagnostic
      systems used. Since BTV propagates readily in experimentally infected T.
      splendens larvae and the BTV antigen can be detected by the fluorescent antibody
      technique with a sensitivity comparable to that for virus propagated in tissue
      culture and embryonated eggs, the TFA system can be adopted as a new method for
      the isolation of BTV from vectors. The advantages of the TFA system are
      discussed.

PMID- 9551485
TI  - Morphological evidence for infection of impala, Aepyceros melampus, platelets by
      a rickettsia-like organism.
AB  - Ultrastructural studies revealed the presence of a parasite, believed to be
      Ehrlichia platys, in the blood platelets of impala. At the time of blood sampling
      all the animals appeared healthy. This is the first report on the presence of
      this rickettsia in these animals, previously described in canine platelets.

PMID- 9551486
TI  - Graph theory and the entropy concept in histochemistry. Theoretical
      considerations, application in histopathology and the combination with receptor
      specific approaches.

PMID- 9551487
TI  - Oesophageal damage and defence in reflux oesophagitis: pathophysiological and
      cell biological mechanisms.

PMID- 9551489
TI  - Psychopathologic domains and insight in schizophrenia.
AB  - The earlier conceptualization of positive and negative symptom topologies for
      schizophrenia has given way to more complex models that propose three-and-four
      dimensions of psychopathology. These constructs may relate to neurobiologic
      heterogeneity and discrete symptom clusters have been shown to have distinct
      anatomical and cognitive correlates. Insight is an excellent example and the
      understanding of insight at psychopathologic and cognitive levels has facilitated
      new approaches to treatment and enhanced medication compliance.

PMID- 9551488
TI  - The new epidemiology of schizophrenia.
AB  - A confluence of findings from different vantage points has led to renewed
      interest and direction in the epidemiology of schizophrenia. This article
      provides an overview of prevalence and incidence data, examining the validity of
      reported secular trends in the occurrence of schizophrenia. Advances in molecular
      genetics have uncovered new linkage on chromosomes 6, 8, and 22 and have
      suggested complex models, including anticipation, to explain the perpetuation of
      genetic transmission in the face of low fecundity. Neurotropic viruses and
      autoimmunity have emerged as pathoplastic mechanisms to explain recent intriguing
      epidemiologic associations in schizophrenia. Environmental risk factors are also
      important. With attention to particular risk factors (i.e., perinatal hypoxia), a
      preventative approach may be realistic for some forms of schizophrenia.

PMID- 9551490
TI  - Child and adolescent schizophrenia.
AB  - Until only very recently, the occurrence of schizophrenia in childhood and early
      adolescence had been largely neglected. Improved diagnostic formulations have
      resulted in clarification of the boundaries between childhood schizophrenia,
      other psychotic disorders, and pervasive developmental disorder. The study of
      schizophrenia in childhood or adolescence provides a unique opportunity to
      examine illness characteristics in the absence of the confounds of substance
      abuse illness, chronicity, and medication effects. Additionally, current
      etiopathologic models of schizophrenia can be tested in this patient subgroup.

PMID- 9551492
TI  - Structural brain imaging in schizophrenia.
AB  - The subtle pathomorphology of schizophrenia is gradually being unraveled through
      the application of increasingly sophisticated brain imaging techniques. There is
      now compelling evidence of subtle brain abnormalities in patients with
      schizophrenia. It less clear, however, whether these reflect a widespread
      cortical involvement, or more selective involvement among interconnected neural
      systems, or more focal pathology. The extent of brain changes, their
      etiopathologic significance, and putative clinical correlates are reviewed in
      this article.

PMID- 9551491
TI  - The neuroanatomy and neurochemistry of schizophrenia.
AB  - Substantial progress, in part owing to recent refinements in methodology, has
      been made in unraveling the anatomic correlates of schizophrenia. Subtle
      pathomorphologic changes, distinct from those of well-known degenerative brain
      disorders, have been observed. Neurochemical characterization has illuminated the
      nature of these morphologic abnormalities and has pointed to complex
      dysregulation of neurotransmitters and G proteins. New biochemical hypotheses
      such as the glutamate hypothesis have replaced and revitalized more established
      concepts in the neurochemistry of schizophrenia.

PMID- 9551493
TI  - Chemical and physiologic brain imaging in schizophrenia.
AB  - Technologic advances in functional brain imaging have provided exciting and
      informative insights into the functional neuroanatomy and neurochemistry of
      schizophrenia. Using MR spectroscopy, it has been possible to examine in vivo
      brain metabolism and to relate observed changes to physiological processes
      occurring at a cellular level. Positron emission tomography and single photon
      emission computed tomography have revealed disturbances of cerebral blood flow
      and glucose metabolism in patients with schizophrenia. More recently, these tools
      have also proved most useful in studying the relative receptor occupancy of
      typical and atypical antipsychotic medications.

PMID- 9551494
TI  - Neurodevelopmental and neuroprogressive processes in schizophrenia. Antithetical
      or complementary, over a lifetime trajectory of disease?
AB  - The neurodevelopmental model of schizophrenia maintains ascendancy among current
      etiopathologic perspectives on schizophrenia. However, inconsistencies across
      studies and the absence thus far of pathognomic brain changes suggest the need
      for complex conceptualization of neurodevelopmental arrest, including some
      reconciliation with the competing neurodegenerative model of schizophrenia. This
      article critically reviews the preponderance of evidence for each model and
      provides an account of how these may interact or synergize to produce the
      characteristic clinical expression of schizophrenia.

PMID- 9551495
TI  - Emerging roles for novel antipsychotic medications in the treatment of
      schizophrenia.
AB  - Antipsychotic medications are the mainstay of treatment for schizophrenia. The
      recent advent of atypical antipsychotics has provided new clinical options and
      set higher expectations for the treatment of schizophrenia. It is not yet clear
      how each different drug will fit within the therapeutic armamentarium and this
      lack is most evident with considering patients with treatment refractory
      schizophrenia. On the other hand, the expectation of superior efficacy, more
      benign side effect profile and potential to impact the longitudinal course of
      schizophrenia provide a rationale for the use of novel antipsychotics as a first
      line treatment of schizophrenia.

PMID- 9551496
TI  - Pharmacoeconomics of the new antipsychotics for the treatment of schizophrenia.
AB  - Inevitably, the greater availability of more costly antipsychotic medications has
      resulted in attempts to regulate the use of these agents. Early objections over
      the cost of treatment with clozapine or risperidone have in part been mollified
      by preliminary statistics on the cost effectiveness of these agents. However,
      this issue is complex and requires careful consideration of pharmacoeconomic
      principles in the development and clinical distribution of novel antipsychotics.
      Future cost-effectiveness studies need to consider a balance of public and
      private perspectives. These studies should be conducted in several settings,
      preferably also within the context of broader, multimodal treatment intervention
      strategies.

PMID- 9551497
TI  - Standards of care and clinical algorithms for treating schizophrenia.
AB  - Health care changes and improved understanding of the course and management of
      schizophrenia have provided the propitious environment to develop guidelines for
      treating patients with schizophrenia. This article describes two recent
      guidelines and highlights how these may be used to enhance clinical practice.
      Although still at a nascent stage that is awaiting more widespread acceptance by
      clinicians, the introduction of guidelines represent a significant advance in
      mental health care.

PMID- 9551498
TI  - Public health policy, community services, and outcomes for patients with
      schizophrenia.
AB  - Amidst the specter of managed care, individual mental health services are
      struggling to redefine their niche, consolidate with partners and provide a
      realistic continuum of care for persons with serious and persistent mental
      illness. Because of the chronicity of schizophrenia, its economic and social
      ramifications, the disparity in health insurance for these patients and limited
      resources, the development of community services has often proceeded in a
      fragmentary manner. Several states have well coordinated community programs with
      integration between private and public services. The Assertive Community
      Treatment (ACT) model has proved successful, although this is costly to maintain.
      Services that synergize optimum pharmacologic and psychosocial treatments can
      achieve favorable patient outcome, as evaluated across clinical, rehabilitative,
      humanitarian, and public welfare domains.

PMID- 9551499
TI  - Advocacy, recovery, and the challenges of consumerism for schizophrenia.
AB  - Advocacy organizations such as the National Alliance for the Mentally Ill (NAMI)
      and patient consumer groups are playing an ever-increasing role in public health
      policy and patient care in schizophrenia. The recovery philosophy which
      recognizes the unique contributions of those who have experienced mental illness
      is now a part of treatment approaches in many states. Several states have
      extended these consumer initiatives to incorporate advance directives, an
      approach that has generated much debate. The NAMI destigmatization campaign,
      grounded in the neurobiology of major mental illness, is an unprecedented,
      concerted effort to change public opinion and to achieve parity at all levels for
      persons with severe and persistent mental illness. This article describes and
      chronicles these initiatives and explores their implications for the management
      of schizophrenia into the next millenium.

PMID- 9551500
TI  - Fatigue in patients with cancer. Analysis and assessment.
AB  - Although fatigue is the most frequent complaint in cancer patients, there is no
      universally accepted definition. In this book a series of studies are presented
      whose aims were definition of cancer-specific fatigue and the development of an
      instrument which had the capacity to discriminate levels of fatigue in different
      groups of cancer patients. The first study (chapter 2) explored the concept of
      fatigue by comparing the personal experiences of cancer patients (n = 20) with
      those of healthy individuals (n = 20). Using grounded theory, themes emerged
      which classified fatigue into physical, affective and congitive components.
      Differences were found in the expressions used by the two cohorts, particularly
      in relation to the physical sensations experienced. The descriptors generated by
      cancer patients were compared with those used in the currently available fatigue
      instruments and illustrated considerable differences in content. They were
      therefore used to develop a new fatigue instrument--the Fatigue Assessment
      Questionnaire (FAQ). The second study (chapter 4) tested the reliability and
      feasibility of the FAQ in a non-randomised, prospective, cross-sectional study of
      cancer patients (n = 77) and healthy individuals (n = 77). It was found to
      discriminate between fatigue experienced by cancer patients and that experienced
      by healthy individuals. A tentative step-like theoretical explanation for the
      production, perception and expression of fatigue proposed at the end of study one
      was supported by factor analysis. It led to minor adaptations of the instrument.
      The third study (chapter 5) subjected the FAQ to further validity testing. Four
      hundred and ninety-nine cancer patients with a variety of tumour types and stages
      were included in a prospective, non-randomised, cross-sectional study. Factor
      analysis supported the theoretical framework and led to modifications which
      resulted in a multi-dimensional, 20-item instrument. The FAQ discriminated
      significantly different levels of fatigue and the distress that it caused in
      patients with metastatic cancer, patients with localised cancer and patients
      whose disease was in remission. High levels of fatigue were mainly associated
      with advanced stages of cancer, in combination with high levels of depression.
      The closing chapter represents a synthesis and discusses issues for further
      research and implications for practice.

PMID- 9551501
TI  - [Effectiveness of partial inpatient rehabilitation from the patient's viewpoint.
      Results of an evaluation of a partial hospitalization model project at the
      Ichenhausen specialty clinic].
AB  - Partial-hospitalization rehabilitation is a relatively recent form of
      rehabilitation, which, as opposed to the ambulatory approach, comprises the
      entire programme available for inpatient medical rehabilitation except for
      accommodation and full board. Great expectations are attached to partial
      hospitalization: it is supposed to cost less than a comparable in-patient measure
      but matching in terms of quality. However, hardly any empirical data exist so far
      concerning the effects partial hospitalization rehabilitation is having in these
      respects. The present article seeks to answer the question of whether from a
      patient perspective, the outcome quality of this new model is comparable to that
      of the classical full-hospitalization programmes. In terms of methodology,
      questionnaires were used to raise the necessary data from two independent samples
      (i.e., partial vs. full hospitalization) of former orthopaedic rehabilitees of
      Fachklinik Ichenhausen (Bavaria). Data analysis included some 205 patient
      questionnaires (57% return rate). High agreement was found among the two groups
      concerning outcome evaluation, subjective health and patient satisfaction. From a
      patient perspective, rehabilitation outcome on the majority of variables
      considered, even is judged slightly better for partial hospitalization patients
      than for the inpatient comparison group. As none of these results reach
      statistical significance, these minor differences should however not be
      overrated. While partial-hospitalization, rehabilitation, hence, has turned out
      an option which matches traditional full-hospitalization programmes in terms of
      quality, too great expectations nevertheless are unwarranted: Partial
      hospitalization rehabilitation is no general alternative to inpatient programmes
      as it will realistically be suitable for a small percentage of orthopaedic
      patients only, hence be unable to replace full-hospitalization programmes to any
      major extent. Undoubtedly, however, it is apt to contribute to greater
      flexibility and needs orientation among the services and programmes available in
      rehabilitation, and may thus be considered a valuable approach for complementing
      inpatient and ambulatory forms of rehabilitation.

PMID- 9551502
TI  - [Psychosomatic-psychotherapeutic rehabilitation of social medicine problem
      patients--an exploratory study of findings, follow-up and treatment outcome].
AB  - The group of social-medical problem patients was defined as comprising those
      patients who are admitted during an on-going invalidity pension award procedure
      or who are drawing a fixed-term pension, patients who have declared their
      intention to apply for pension award and/or have been on sick leave for an
      uninterrupted 6 months at the time of admission. In light of this definition,
      some 25-30% of the patients referred to us would be considered social-medical
      problem patients. The main focus of the present study had been to identify the
      subgroup of patients who might be expected to profit from psychosomatic
      rehabilitation notwithstanding their social-medical problems. Improvement in
      physical symptoms was achieved in 34% of the patients, and in 43% relative to the
      psychological symptoms present. The group of patients showing the greatest
      measure of improvement can be described by the following prognostically
      favourable factors: incapacity for work at the time of admission but no
      application for pension award made or planned; lower average age, higher
      motivation on admission, and lower severity of the social-medical problems, no
      denial of psychosocial factors, and willingness to join group psychotherapy.
      Prognostically unfavourable factors were found to be a fixed-term pension already
      awarded, along with repeated participation in rehabilitation measures on purely
      somatic grounds, and a higher age. Pertinent literature is reviewed in light of
      these findings, underscoring the significance of the time factor in
      chronification of neurotic disorders of the capacity for work and gainful
      activity. Consequently, these patients should as speedily as possible undergo
      efficient psychosomatic diagnosis and be referred for inpatient psychosomatic
      rehabilitation.

PMID- 9551503
TI  - [Changes in pensioning and psychosomatic assessment].
AB  - Appropriate evaluation of a patient's handicapping or disabling conditions, of
      his or her capacity for work and gainful activity rank among the recurring tasks
      in inpatient rehabilitation. Published recently, the Beeintrachtigungsschwere
      Score (BSS; a score for determining the severity of a condition) constitutes a
      highly practicable instrument for these purposes, well suited to the clinical
      setting. Particular difficulties are encountered in the assessment of patients
      already in the pension award process, a population where the original disease
      picture has been superimposed by numerous chronification factors of a
      psychological, social and economic nature so that a so-called invalidity
      pensioning career has set in. The article gives an overview of this phenomenon of
      invalidity pensioning career and the sequence of its various phases, setting out
      the use of the BSS for social-medical evaluation in an inpatient rehabilitation
      setting.

PMID- 9551504
TI  - [Psychosocial predictors for initiating a pension procedure after bypass
      operation].
AB  - From the psychologist's point of view, a routine coronary artery bypass operation
      is often looked upon by patients as a negative situation. The patient develops
      the feeling that his or her life has been dramatically altered, thus the patient
      feels he must somehow make a change in the upcoming pattern of the future. The
      patient, as well as his employer, is convinced of subjective models of etiology,
      which cause the attitude that circumstances of living must change rapidly. In
      this context continued employment is viewed as a significant burden and
      hindrance, despite an excellent post-operative discharge diagnosis. According to
      the hypothesis, emotions and attitudes directly concerning the working
      environment, that lead to an application for early retirement should be
      identified. Medical and psychological counseling before surgery and post-op
      rehabilitation, should be carried out to ease the obsession with early retirement
      and prevent possibly following psychopathological disturbances.

PMID- 9551505
TI  - [Computer-assisted stress analysis in rehabilitation with ABBA (job requirements
      and capacity analysis)].
AB  - ABBA is a recently devised, ergology-based expert system software for vocational
      analysis, documentation and evaluation--inter alia in the context of medical and
      vocational rehabilitation-, drawing on some 20 years of experience in job
      analysis with the AET (Arbeitswissenschaftliches Erhebungsverfahren zur
      Tatigkeitsanalyse). Designed for broad and differentiated coverage, a PARADOX
      data bank comprising the entire data collected enables comparison of job
      requirements and client performance potential, reaching for beyond individual
      analysis on account of its integration of job profiles for a given industry or
      occupation, or for an entire company. The related, and easy-to use, software for
      data processing and appraisal is now being made available by ABBA along with
      dialogue-based ergological know-how.

PMID- 9551506
TI  - [Experiences and effects with 6 years of judo training in ambulatory
      rehabilitation of bronchial asthma in childhood].
AB  - In view of backing up the potential for as normal a life as possible in the
      presence of chronic obstructive respiratory disease, quality rehabilitation
      concepts have for some ten years been discussed which recommend satisfactory
      levels of motor activity in particular during childhood and youth as a factor in
      stabilizing long-term health. A difficult prerequisite in this respect is
      choosing a sport adapted to the child's age and condition as well as providing
      adequate motivation, along with awareness of exercise- and training-induced
      stress and strain reactions. Several years of experience with Judo have shown
      that, in an ambulatory rehabilitation setting, the needs of schoolchildren with
      bronchial asthma too, may be answered by this competitive sport provided that
      several didactic and methodological premises are heeded. In light of its holistic
      educational approach and intermittent stress and strain profile, Judo is cut out
      for facilitating integration in the social community, hence contributing toward
      valuable personality characteristics and growth in a rehabilitative context in
      the face of the long-term course of the illness.

PMID- 9551507
TI  - [Prohibiting prejudice against handicapped students in schools].

PMID- 9551508
TI  - [The Duke Severity of Illness Checklist].
AB  - Developed at the Duke University Medical Center of Durham, North Carolina,
      U.S.A., the Duke Severity of Illness Checklist (DUSOI) is a tool for measuring a
      person's illness severity. The instrument comprises four parameters of a health
      problem, e.g. in a given diagnosis, namely: symptoms, complications, 6-months
      prognosis without treatment, treatment potential. Using the numerical ratings
      (from 0 to 4) for each parameter of every diagnosis, the following three types of
      severity score (from 0 [lowest degree of severity] to 100 [highest degree of
      severity]) can be calculated: (1) the DUSOI diagnosis score for each diagnosis
      stated, (2) the DUSOI overall score for the set of all health problems stated for
      a patient, and (3) the DUSOI comorbidity score, i.e., all problems except for any
      one problem of principal interest. The DUSOI is suitable for patients from the
      entire chain of medical and rehabilitative care, although it had initially been
      developed for the ambulatory sector. Completing the DUSOI form is very economical
      in terms of time needed, and is recommended to be done by the physician in charge
      immediately following the patient's visit. Alternatively, the form could also be
      filled in by a reviewer on the basis of the patient's medical record. A certain
      level of judgement is required on the part of the physician or reviewer carrying
      out the DUSOI assessments.

PMID- 9551509
TI  - [The study of bronchial hyperreactivity in children].

PMID- 9551510
TI  - [Asthma and household chemical pollutants (with the exception of tobacco)].
AB  - The relationship between allergens in a domestic environment and asthma has been
      extensively studied and it is only recently that studies have suggested the
      possibility of the role of chemical pollutants in the internal environment in the
      genesis of asthma. The pollutants studied are oxides of nitrogen (nitrogen
      dioxide NO2), volatile organic components (COV), formaldehyde, ozone (O3) and
      sulphur dioxide (SO2). The level of nitrogen dioxide in the interior of houses
      may be greater than those met outside. Normal values are 400 mcg per metre3 per
      hour and 150 mcg per metre3 in twenty four hours. In asthmatics challenge test to
      nitrogen dioxide and epidemiological studies suggest that internal nitrogen
      dioxide is capable of provoking asthmatic crises either by a direct pollutant
      effect or by potentialising the allergenic crises either by a direct pollutant
      effect or by potentialising the allergenic response of the bronchi. COV and
      formaldehyde are liberated by urea formaldehyde foams and by chipboard furniture.
      The levels of COV and formaldehyde inside a house may be up to 10 times higher
      than those outside. COV and formaldehyde perhaps would have an effect on the
      bronchi in asthmatics at significant levels which are rarely found in the
      domestic environment. Ozone is an external pollutant. However, from 5-80% of the
      external concentrations may be found inside some locations. Thus, in certain
      conditions which are relatively rare, the interior concentrations of dwelling
      places may attain levels which are capable of inducing, in healthy subjects who
      are sensitive to ozone, a drop in the FEV1. As regards asthmatics, only
      experimental work has been able to show any bronchospastic effect of ozone,
      either by a direct effect on the bronchi or by the potentiation of a bronchial
      response to allergens. It would be convenient to perform some epidemiological
      studies to determine if there is a relationship between exposure to ozone
      internally and to bronchial changes. The concentrations of SO2 inside houses
      increases when coal is burnt. The levels provoking a bronchial reaction are much
      greater than those found inside houses. The data and the literature which is
      mostly recent seems to stress the role of NO2 ozone and SO2 as a factor which
      might favour asthmatic crises induced by allergens in atopic subjects. However,
      other studies will be necessary to confirm the initial data.

PMID- 9551511
TI  - Long-acting beta-2 agonists. An attempted response to various questions which can
      be posed by pneumonologists.
AB  - The use of long acting beta 2 agonists is an undeniable improvement in the
      treatment of certain types of asthma. It enables better control of unstable
      asthma, improves and gives a superior quality of life. Current work confirms
      however that when used in the long term they ought to be associated with anti
      inflammatory treatment. If they do not produce any important secondary effects,
      even when used for a long period, it is not currently possible to confirm that
      their prolonged use does not change the intensity of their bronchodilator effect
      and/or the intensity of the bronchodilator effect of the short acting beta 2
      stimulants. Some studies have shown that their addition to basic treatment with
      inhaled steroids is more effective than increasing the inhaled steroids. Other
      studies are necessary to know if they may enable the reduction in inhaled
      corticosteroids and how far.

PMID- 9551512
TI  - [The effect of corticotherapy on respiratory muscles].
AB  - Skeletal muscle myopathy is one of the main side-effects of systemically
      administered corticosteroids, and involves respiratory as well as peripheral
      muscles. After prolonged treatment with moderate doses of either fluorinated or
      non-fluorinated corticosteroids, chronic myopathy may occur. In patients, such
      myopathy is characterized by the gradual onset of proximal limb muscle weakness
      and a sudden increase in creatine excretion in 24h urine. This myopathy is
      associated with a generalized fiber atrophy of the quadriceps in which myopathic
      changes are present. Since these changes were also observed in animal models, it
      was concluded that steroid treatment was responsible for them. After cessation of
      treatment, recovery of muscle force occurs but may be protracted. The severity of
      corticosteroid-induced myopathy appears to depend upon the type of steroid used,
      the treatment duration, the dose and the treatment regimen where repetitive burst
      treatment effects are worse than those obtained with continuous treatment with
      the same dose. During short-term treatment with massive doses of corticosteroids
      as frequently used to treat status asthmaticus, acute myopathy may develop and is
      characterized by generalized fiber necrosis and rhabdomyolysis. Because such
      necrosis was not observed in animal studies, it was suggested that the necrosis
      may result from the combined effect of corticosteroids with other agents such as
      aminoglycoside antibiotics and/or muscle relaxants.

PMID- 9551513
TI  - [The contribution x-ray computed tomography in chronic diffuse infiltrative lung
      disease].
AB  - Computed tomography (CT) may be useful at all stages of management of chronic
      infiltrative lung disease. It contributes to diagnosis and evaluation of
      inflammation and fibrosis, helping the therapeutic decision and appreciating the
      response to treatment. It contributes to follow-up in the course of the disease.
      Some further works are necessary to know the indications of CT and the frequency
      of examinations.

PMID- 9551514
TI  - [The value of surgery in the treatment of invasive pulmonary aspergillosis in
      neutropenic patients].
AB  - The aim of the study is to specify the indication for surgery in the treatment of
      invasive pulmonary aspergillosis (API). From January 1991 to October 1996
      nineteen patients who had been treated with chemotherapy and associated marrow
      aplasia and suffering from API were operated on. At the time of the surgical
      intervention all of the patients were treated with antifungal drugs. The delay
      between the start of their symptoms and the start of treatment was 2.6 days
      (range: 0-17 days). 1. The risk of a massive haemoptysis by contact between the
      fungal infection and the pulmonary artery led to eight urgent surgical
      operations: six lobectomies and two lobectomies associated with segmentectomy.
      The mean level of polymorphonuclear neutrophils was 296 cell/mm3 (0-1,000).
      Plastic surgery on the pulmonary artery was carried out in three patients. One
      patient died after the operation with progression of the API. The duration of
      postoperative stay was 13 days (6-18). 2. Planned surgery consisted of a
      resection of the residual mass after antifungal treatment and a diagnostic
      approach to the intraparenchymatous mass of indeterminate aetiology. A resection
      of the residual masses (in spite of antifungal treatment) was carried out in
      seven patients: before further haematological therapy in six cases and in one
      case for a superinfected lesion. The type of resection was: a lobectomy (n = 4),
      a lingulectomy (n = 1) and an atypical resection (n = 2). No postoperative deaths
      were reported. The patients left the surgical service between the seventh and
      twentieth day postoperatively. The surgery was used in four patients as the
      diagnostic approach in view of intraparenchymal masses of unknown aetiology and
      had enabled a fungal mycelium to be isolated at the centre of persisting
      inflammation. Antifungal treatment sometimes associated with surgery allowed for
      a better prognosis in patients suffering from invasive pulmonary aspergillosis.

PMID- 9551515
TI  - [Oxygen transport capacity of blood in athletes with malarial infection].
AB  - The purpose of the present investigation was to examine the effects of the
      malaria parasite on the oxygen capacity of blood. 15 males basket-ball players
      (mean +/- SE: age: 17-30 +/- 1,44 years; weight = 63.20 +/- 6.55 kg; height:
      177.99 +/- 0.10 cm) were volunteered to take part in this study. Nine subjects
      were infected by the malaria parasite, but seemed healthy. Six other subjects
      were really healthy. The oxygen capacity of blood was decreased in the infected
      group when compared with the noninfected group (15.86 +/- 1.59 ml vs 17.64 +/-
      0.62 ml) (p < 0.05). The comparison of all other hematologic data showed them all
      reduced in the infected group: total number of erythrocytes = 4.90 +/- 0.50 x
      10(9)/ml vs 5.03 +/- 0.33 x 10(9)/ml (p < 0.05), mean cellular volume (CMV):
      71.75 +/- 6.37 fl vs 77.67 +/- 5.74 fl (p < 0.01), hemoglobin concentration
      ([Hb]): 11.84 +/- 1.19 g/100 ml vs 13.16 +/- 0.46 g/100 ml (p < 0.05),
      hematocrit: 35.22 +/- 2.86% vs 38.93 +/- 1.18% (p < 0.05). The chronic anemia
      induced by the malaria might theorically limit the oxygen capacity of blood,
      which constitutes an important factor for the aerobic performance.

PMID- 9551516
TI  - [Patent and occult intra-alveolar hemorrhage in leptospirosis].
AB  - PURPOSE: Pulmonary involvement (PI) is common in leptospiral infection, usually
      characterized by hemoptysis and diffuse bilateral infiltrates on chest
      radiographs. Alveolar haemorrhage (AH) has already been proved by autopsy and
      some case-reports with fiberoptic bronchoscopy (FB) and bronchoalveolar lavage
      (BAL). The purpose of this study was 1/to evaluate the incidence of AH in
      leptospirosis 2/to define the impact of BAL on the early diagnosis of the
      infection. PATIENTS AND METHODS: FB with BAL were performed in 23 consecutive
      patients with leptospirosis (13 patients with patent signs of PI: group 1, 10
      patients without: group 2). AH was defined by a percentage of siderophages > or =
      20% and/or a Golde score > 100 and/or an haemorrhagic aspect of BAL fluid.
      Culture tests were performed on specific medium. RESULTS: We diagnosed AH in all
      patients of group 1 and in 7 patients of group 2. Filaments were seen in 6
      specimens of BAL fluid, initially thought to be leptospires, but culture tests
      were negative. CONCLUSION: AH is identified in all cases of leptospirosis with
      PI. Occult AH often occurs to patients without any respiratory symptom.
      Physicians should consider leptospiral infection in the differential diagnosis of
      AH. Culture-tests for leptospirosis in BAL do no help in diagnosing
      leptospirosis.

PMID- 9551517
TI  - [Chronic obstructive pulmonary disease patients undergoing home oxygen therapy: a
      study of clinical parameters, nutritional status and ambulatory capacity].
AB  - AIM OF THE STUDY: The aim of the study was to document the nutritional status and
      the calorie demands of patients suffering from severe chronic airflow obstruction
      (BPCO) who were on continuous domiciliary oxygen therapy (OCD) and to correlate
      this information with the clinical picture, the severity of the respiratory
      disease and the daily distance walked, this to be measured in a prospective
      manner. PATIENTS AND METHODS: Fifty clinically stable patients with chronic
      airflow obstruction on continuous oxygen therapy for 33 months (range 4-106) in
      whom the following measures were made at home: pulmonary function, maximal static
      inspiratory and expiratory pressure (PIMAX and PEMAX), strength of hand, grip,
      the mean distance walked daily (wearing a pedometer for one week), body mass
      index (IMC), and the body composition by electrical bio-impedence and calorie
      requirements. RESULTS: Thirty four per cent of patients presented with an
      excessive body mass (IMC > 27 kg/m2), 42 per cent had normal nutrition (IMC 20-27
      kg/m2) and 24 per cent were malnourished (IMC < 20 kg/m2). Malnourished patients
      had, in a statistically significant manner, airflow obstruction of greater
      severity and a lower oxygen saturation and a PEMAX as well as a lower daily
      distance compared to over weight subjects. However, their net calorie
      requirements were markedly higher (39 +/- 5 Kcal/kg/j) compared to patients
      having normal weight (29 +/- 11 kcal/kg/j) or excess weight (25 +/- 8 kcal/kg/j).
      From the clinical standpoint no malnourished patient fulfilled the clinical
      criteria of chronic bronchitis. By contrast 61 per cent of subjects with normal
      nutrition and 94 per cent of subjects with excessive weight were chronic
      bronchitics. CONCLUSION: In the group of patients with severe airflow obstruction
      on domiciliary oxygen, 25 per cent were malnourished and this was in spite of
      netly increased calorie consumption which is superior to their theoretical need.
      This suggests that the solution of increasing supplements to their dietary
      requirements would be a difficult to realise. These subjects presented also with
      a more marked ventilatory handicap and a clinical picture characterised by the
      absence of the classical signs of chronic bronchitis.

PMID- 9551518
TI  - [Attitude and behavior of hospital personnel toward smoking].
AB  - Due to a lack of data available at the national level, on smoking behaviour of
      hospital staff, a survey was carried out in a representative sample of hospitals.
      This survey, which will be repeated in the future, should enable to evaluate
      preventive actions at hospital and to measure the implication level of the
      hospital staff in tobacco prevention. The analysis of data collected among 3082
      persons shows that a third of the hospital staff smokes. Among these persons a
      certain part smoke at their working place, this proportion is varying
      considerably with the working area in the hospital. The more this area is close
      to the patient the less is hospital staff smoking. More than one third of the
      interviewers (37.3%) think that trying to convince people to stop smoking is part
      of their role: this opinion varies considerably depending on the professional
      activity in the hospital. In addition a very large majority (81.4%) of the
      hospital staff considers that it has an exemplary role to play in front of
      patients. This belief is shared equally by all the different groups of staff. The
      smoking prevalence among hospital staff is equivalent to that of the general
      population; this underlines the need and the necessity to realize anti-tobacco
      campaigns among this health care population. Moreover since the exemplary role
      they have to play, is very well accepted, preventive actions could rely on a good
      level of participation.

PMID- 9551519
TI  - [Bronchial casts associated with pulmonary lymphatic anomalies].
AB  - We report a case of a patient who presented with bronchial moulds. The classic
      causes, particularly bronchopulmonary aspergillosis could not be found. The
      pulmonary radiology and CT of thorax revealed an alveolar syndrome. Lymphography
      and lymphoscintigraphy showed evidence of lymphatic anomalies including the non
      visualisation of the thoracic canal. In the absence of evidence for other
      diseases, we would suggest that these anomalies were responsible for the
      symptomatology.

PMID- 9551520
TI  - [Tumors of the phrenic nerve].
AB  - A schwannoma of the phrenic nerve is a rare disorder which presents as a tumour
      of the anterior mediastinum. It is seen in adults and is usually latent. We
      report two cases in elderly subjects in whom the phrenic nerve tumour had
      achieved a significant size. One of these schwannomas had degenerated into
      sarcomatous change which is the first case reported to the present time.

PMID- 9551521
TI  - [Pulmonary artery hypertension in HIV seropositive drug addicts. Apropos of 10
      cases].
AB  - Pulmonary hypertension (PH) is a classic complication associated with intravenous
      drug addiction. Various pathogenic mechanisms may be involved but HIV infection
      now appears to be the main etiologic factor. We report herein 10 case of PH
      occurred in HIV+ intravenous drug abusers. Each patient had several pathogenic
      factors: HIV infection, pills crushed and intravenously injected (6 cases), heavy
      and repeated consumption of amphetamines and cocaine (6 cases), cirrhosis with
      portal hypertension (2 cases), anticardiolipid antibodies (2 cases). The clinical
      findings were similar to those reported for PH in HIV seronegative patients;
      however, in 5 cases, opiates could have alleviated dyspnea, which became
      perceptible only at the time of drug withdrawal. Because drug addicts usually
      exhibit a weak support for medical prescriptions, long term therapy needing
      regular follow-up such as anticoagulation appears to be hazardous and even
      dangerous. The prognosis remains poor, since the progression of PH led to the
      death of one third patients within the year following the diagnosis.

PMID- 9551523
TI  - [Very atypical lung disease].

PMID- 9551522
TI  - [Percutaneous closure of an right-left interatrial shunt acquired after
      pneumonectomy].
AB  - Right to left shunt through a patent foramen ovale after pneumonectomy is a rare
      complication. Its clinical presentation is a severe dyspnea with posture
      dependency. The diagnosis is easily confirmed by contrast echocardiography. The
      purpose of this article is to expose the interest of interventional
      catheterization and transcatheter closure. This method appears to be a viable
      alternative to surgery for those patients with precarious respiratory function.

PMID- 9551524
TI  - Clinical evaluations of dorsiflexion assist controlled by spring ankle-foot
      orthosis for hemiplegic patients.
AB  - To examine the usefulness of Dorsiflexion Assist Controlled by Spring Ankle-Foot
      Orthoses (DACS-AFO), 5 hemiplegic patients in Brunnstrom's recovery stage IV were
      prescribed the DACS-AFO, after which their gait with the DACS-AFO was clinically
      evaluated. Clinical observation did not reveal that their gait with the DACS-AFO
      was better than that with an AFO which the patients usually used, except when one
      patient walked on a slope. No significant difference in 10 m walking time was
      found between when the DACS-AFO and shoehorn type AFO were used. Subjective
      evaluations by the patients indicated that the DACS-AFO was as good as a shoehorn
      type AFO in walking on flat and sloped surfaces, though its weight, noise, and
      appearance caused by the cylinder of the DACS-AFO were regarded as poor. In spite
      of the excellent biomechanical characteristics of the DACS-AFO, the patients did
      not adopt it. The subjects in this study had already walked well with their own
      shoehorn type AFO, and their selection may have been biased toward poor results.
      However, we did not conclude that the DACS-AFO is superior to the shoehorn type
      AFO for hemiplegic patients in the stage IV.

PMID- 9551525
TI  - Pathological study of splenomegaly associated with cadmium-induced anemia in
      rats.
AB  - Splenomegaly was observed both in male and female Sprague-Dawley rats after 1
      week of exposure to CdCl2 (0.6 mg Cd/kg/day). Spleen weight reached about double
      that in controls by 8 weeks of Cd exposure. Histopathological examination of the
      enlarged spleen revealed that iron- and lipid-laden histiocytes were clustered in
      the periarterial lymphatic sheath, and the red pulp appeared to be expanded. It
      is noteworthy that electron microscopy revealed marked poikilocytosis and Heinz
      body formation in red blood cells (RBCs) in both the sinus and cord. Histiocytes
      were swollen by a granular substance in the cytoplasm and also many secondary
      lysosomes. These morphological findings indicate that degradation of damaged RBCs
      induced by exposure to Cd might be promoted in the spleen and possibly cause
      splenomegaly. This RBC damage-hemolysis-splenomegaly sequence is also considered
      to be associated with the etiology of Cd-induced anemia. In addition to the
      abnormal RBC degradation, nuclei of lymphocytes in the Cd-exposed spleen
      exhibited high electron density, consistent with a preapoptotic state suggesting
      the immunosuppressive effect of Cd.

PMID- 9551526
TI  - [Two-phase helical hepatic CT. Contrast-injection protocol, optimal timing and
      its usefulness in clinical cases].
AB  - The usefulness of two-phase helical computed tomography (CT) of the liver was
      evaluated in clinical cases. First, an optimal scanning protocol was determined
      using time-attenuation analysis. Monophasic dynamic CT was performed with 100 ml
      of contrast media (iodine 300 mg/ml) injected either at 3 ml/s or at 2 ml/s.
      Aortic, hepatic and portal time-attenuation curves were made for each protocol.
      The results showed that these two different injection protocols produce
      equivalent enhancements and that the injection rate of 2 ml/s is satisfactorily
      applicable to clinical cases. The first scanning (arterial phase) must be started
      40-45 s after the beginning of the injection of contrast media and the second
      scanning (delayed phase) 80-120 s after the beginning of injection. Using these
      CT protocols, 327 cases were examined. In this study 83 hepatic lesions
      (hepatocellular carcinoma : HCC, n = 29; suspected HCC, n = 30; hemangioma, n =
      24) were evaluated. There were 15 HCCs smaller than 30 mm in diameter (71.4%)
      detected by either arterial phase or delayed phase alone. This result indicates
      that two-phase helical hepatic CT is very useful in the detection of small HCC.
      Particularly, four of 5 HCCs of less than 10 mm in size (80%) showed a
      hyperattenuation area in the arterial phase alone. HCCs which have sufficient
      vascularity were also easily demonstrated. However, this two-phase helical
      hepatic CT could not demonstrate 11 lesions (13.3%) with almost normal blood
      supply. In such cases the complementary role of ultrasound (US) seems to be
      important. Hence as a screening of hepatic mass lesions both CT and US are
      necessary. Most HCC could be differentiated from hemangioma by an enhancement
      pattern using this protocol. But the small liver lesions of less than 15 mm in
      size with homogeneous hyperattenuation in the arterial phase and isoattenuation
      in the delayed phase included HCC, hemangioma and metastatic tumors.

PMID- 9551527
TI  - Comparison of the qualified occupational physician systems in the United Kingdom
      and Japan.
AB  - The British educational system of occupational medicine was compared to the
      Japanese system. Furthermore, a comparison was carried out between the certified
      occupational physician (COP) recognized by the Japan Society for Occupational
      Health in Japan and the Associateship of the Faculty of Occupational Medicine
      (AFOM) by the Faculty of Occupational Medicine (FOM) which is a part of the Royal
      College of Physicians in the United Kingdom. Judging from the comparison of the
      minimum total training period, the clinical training period, the occupational
      health training period, the method of examination and the success rate between
      COP and AFOM, it is suggested that the British system of occupational physicians
      may be better as a training system for occupational medicine and may regard
      occupational clinical training as more important than the Japanese system does. A
      comparison of a Diploma in Occupational Medicine (Dip Occ Med) approved by the
      FOM and the certification of occupational physicians by the Japan Medical
      Association has shown that the former has an examination but there is no test
      system in the latter. It should be discussed whether an examination system for
      the certification of occupational physicians should be introduced into the
      Japanese system in the near future.

PMID- 9551528
TI  - [Virulence factors and host responses in urinary tract infections].
AB  - Pathogenicity of urinary tract infection (UTI) has been reviewed mainly focussing
      on the bacterial adherence in uropathogens and the inflammatory responses of
      urinary mucosa. Bacterial fimbriae or pili, which are encoded by chromosomal gene
      clusters played a major role in the adherence mechanisms of uropathogenic
      bacteria, including Escherichia coli. Furthermore, inflammatory responses in
      urinary mucosa including cytokine release was also investigated. The latest
      information concerning pathogenicity of UTI is described and discussed here.

PMID- 9551529
TI  - [Expertise in occupational health nursing (I). Report on a visit to US
      occupational health institutions].
AB  - As industries' structures have evolved and diversified recently, the framework of
      occupational health nursing has been expanded on multidisciplinary bases. On the
      occasion of the opening of the School of Health Sciences, University of
      Occupational and Environmental Health, Japan (UOEH), the author was given an
      opportunity to visit US administrations, academic institutions and some
      industries to investigate occupational medicine and health nursing in that
      country. And as the author took part in programming the 17th UOEH International
      Symposium on Occupational Health Nursing Expertise that took place at the campus
      of the University in October, 1997, these two events are reported in this paper.
      The first part of the report is on the visit to the US occupational health
      professionals including occupational health doctors, nurses, industrial
      hygienists and other staffs. They have perceived that there has never been more
      emphasis placed on the significance of occupational health services than in
      recent years, and that young students have become more interested in occupational
      health. The second report will be on the 17th UOEH International Symposium-
      Occupational Health Nursing Expertise--the next time.

PMID- 9551530
TI  - [Diversity of P 450: biology and application of diversozyme].
AB  - Cytochrome P 450s (P 450s) are a gene superfamily of heme enzymes involved in
      xeno-or endo-biotic metabolisms. They have approximately 500 isozymes via
      evolution, immense diversity in their functions and a broad range of substrate
      specificities. Thus, they are called diversozymes and their versatility is
      understood as a mechanism for living via detoxification of toxicants. However,
      some of the huge human-made chemicals are bioactivated by P 450s. To explain
      diversity of P 450s, further studies regarding relations between crystal
      structures and functions of P 450s are required. P 450s can be applied for
      exposure-biomarkers of environmental pollution, screening of drug metabolism and
      remedy for pollutants.

PMID- 9551531
TI  - [Simultaneous laparoscopic therapy of cholecysto- and choledocholithiasis. An
      analysis of results].
AB  - INTRODUCTION: With the advent of laparoscopic cholecystectomy, ERCP has gained
      importance in the treatment of choledocholithiasis. Laparoscopic cholecystectomy
      with intraoperative cholangiography and common bile duct surgery allows diagnosis
      and treatment of cholecystolithiasis and choledocholithiasis in a single
      procedure. PATIENTS AND METHODS: Laparoscopic treatment of choledocholithiasis
      was evaluated in 99 consecutive patients with choledocholithiasis. 28 patients
      underwent successful preoperative ERCP. Of the patients with intraoperative
      confirmation of choledocholithiasis, removal was attempted by a transcystic
      approach in 36 and 23 underwent choledochotomy. 24 patients with a high operative
      risk underwent postoperative ERCP. RESULTS: The transcystic approach was
      successful in 72.2%. Choledochotomy was successful in 91.3%, yielding a combined
      success rate of 80%, 3.4% had local complications and 8.4% had other
      complications (complication rate 11.8%), 20.3% of the patients underwent ERCP
      after failed laparoscopic procedures. One patient had a laparoscopic redo. There
      was no mortality and no conversion to open surgery. CONCLUSION: ERCP and
      laparoscopic common bile duct surgery are complementary, efficient and safe
      modalities of treatment for choledocholithiasis. Choice of procedure is
      influenced by the surgeon's experience and institutional infrastructure, and the
      individual patient.

PMID- 9551532
TI  - [Surgery of mitral valve insufficiency. Results of 10 years].
AB  - From 1987 to 1996 we operated on 263 patients for mitral insufficiency. Multiple
      valve operations were excluded, with the exception of tricuspid reconstruction
      for functional regurgitation. The perioperative mortality was 3%, while the late
      mortality rate during a mean follow-up period of 3.5 years amounted to 2% per
      patient year and 1.7% if only cardiac causes were considered. The prognosis for
      patients with rheumatic, endocarditic and ischemic valvular disease was much
      worse compared to that for a degenerative cause. The latter group consisted of
      209 patients with an operative mortality of 1.4% and a late mortality rate per
      patient year of 1.4% and 0.9% for cardiac causes only. Further analysis showed a
      significant prognostic improvement for patients with a preoperative ejection
      fraction of more than 60% and a repairable valve.

PMID- 9551533
TI  - [Hypokalemic periodic paralysis: new advances].
AB  - We present a 56-year-old man with an episode of hypokalemic periodic paralysis.
      There are several interesting aspects of this rare disease, such as the
      suggestive history and clinical signs (sudden onset, symmetrical paralysis mainly
      of the lower extremities, "walking-off" phenomenon, no symptoms or signs between
      attacks) or the unexplained episodic character of the attacks. It belongs to the
      recently recognized ion channel diseases, a group of disorders in which mutations
      of genes encoding the channel protein are responsible for defective channel
      function. Molecular studies of mutated channels or channel subunits should
      provide insight into channel functioning and help to develop effective drug
      treatment. Once diagnosis of hypokalemic periodic paralysis is established,
      treatment and regular follow-up are necessary to prevent the development of
      permanent muscle weakness. The increasing mobility of the world's population will
      add to the frequency of thyrotoxic hypokalemic periodic paralysis (which is
      relatively frequent in Asian populations) even in Western countries.

PMID- 9551534
TI  - [Hypermobility syndrome. When too much activity causes pain].
AB  - Hypermobility of joints and spine is a consequence of abnormal laxity of
      ligaments, joint capsules and intervertebral discs. Hypermobility per se is a
      state, not a disease. However, it may lead to generalized arthralgia or localized
      symptoms (frequent ankle sprains, knee effusions, dislocations of the shoulders
      of recurrent episodes of back pain). These events may occur even after minor
      strains. Young women are preferentially affected. The term "hypermobility
      syndrome" is defined as a combination of hypermobility with arthralgia, low back
      pain, frequent dislocation or sprains. It is often the result of a hereditary
      disorder of connective tissue. Individuals with hypermobility are at increased
      risk for premature osteoarthrosis or polytopic disc degeneration of the spine.
      However, the vast majority of hyperlax individuals are free of symptoms. Those
      with symptoms who do not develop osteoarthrosis or disc degeneration usually
      experience spontaneous improvement with increasing age, thus losing their
      juvenile hyperlaxity. This usually occurs between the ages of thirty and forty.
      The present review article also provides guidelines for management and patient
      information.

PMID- 9551535
TI  - [PPPP (post-proctoscopy periorbital purpura)].

PMID- 9551536
TI  - [A temporary reduction of emotional reactivity in postweaning, prejuvenile rats:
      examination by the Runway Test].
AB  - Developmental change of emotional reactivity in Wistar rats was investigated by
      two experiments using the Runway Test. Rats were tested at 20, 30, 40, 60, and 90
      days of age for three successive days. First, a cross-sectional comparison of
      behavior in the Runway Test showed that 30-day-old rats were faster to enter the
      runway region, faster to reach the end section, and traversed more sections than
      other age groups. Rats at 60 and 90 days of age defecated more bolles and
      urinated more. Second, longitudinal comparisons showed that the ambulation of 30-
      and 40-day-old rats increased gradually over test days, suggesting lowered
      emotional reactivity. But 60- and 90-day-old rats showed asymptotic level of
      ambulation and no increase between days and less defecation. These results
      suggested that postweaning prejuvenile rats showed a temporary reduction of
      emotional reactivity in novel environments. Also, their emotional reactivity
      elevated gradually, and remained stable in each individual level.

PMID- 9551537
TI  - [The effects of self-perception and attitudes to cultures on international
      students' feeling of adjustment].
AB  - Asian students of seven Japanese language schools participated, and data of 292
      Chinese, Taiwanese, and Korean students were analyzed in this study. They were
      asked about (1) attitudes toward their own and other cultures, (2) high regard
      for their country and culture, (3) self-efficacy and social skills at the moment
      and when they were in their country, (4) aspired level of social skills in this
      country, and (5) feeling of adjustment to life in Japan. Main findings were as
      follows: (1) psychological factors had stronger effects on the feeling than
      demographic factors. Self-efficacy in particular had a strong effect. (2)
      Attitudes to own and other cultures were related to self-efficacy and the
      feeling. (3) Structural analysis revealed a difference in the feeling between
      students from socialist and capitalist regions. Based on the analysis, a causal
      model was proposed of psychological and demographic factors leading to feeling of
      adjustment, and Asian students' adjustment to life in Japan was discussed in
      terms of adjustment to their inner, psychological environment.

PMID- 9551538
TI  - [Effect of vibrational factors on the evaluation of whole-body vibrational
      intensity].
AB  - The aim of this study is to obtain basic data useful to evaluate the riding
      comfort of railway vehicles. The apparatus used in the present experiment made it
      possible to simulate various vibrations of railway vehicles. Twenty-two adult
      subjects participated in this experiment. They were exposed to lateral vibration
      with varying peak and root mean square (rms) accelerations and frequencies. The
      types and ranges of vibrations used in this experiment approximated to the
      typical vibrations of railway vehicles. The subjects were asked to rate the
      intensity of each vibration given to them successively, using the 7-step rating
      scale. Results indicated that both peak and rms accelerations significantly
      affected for the evaluation, although the effect of frequency was not
      significant. As for interactions, it was found that there were significant
      interacting effects between frequency and peak acceleration, between frequency
      and rms acceleration, and between peak and rms accelerations. It was also found
      that the relationship between the rms acceleration and the evaluated score
      changed with varying peak accelerations.

PMID- 9551539
TI  - [The effects of subliminal and supraliminal presentation of trait-related words
      on person perception].
AB  - The present experiment was conducted to investigate how prior information affects
      subsequent person perception and when perceivers can control such an effect. One
      of three types of trait related words (i.e., hostility-related, friendliness
      related, and neutral words) was subliminally or supraliminally presented to
      subjects, and subsequently, subjects rated the impression of four targets: a
      hostile person, a friendly person, a neutral person and themselves. Although
      results did not show that supraliminally presented words affected targets'
      impressions, they showed that the impressions sometimes varied with the valence
      of subliminally presented words regardless of targets' valence. The mechanism and
      controllability of priming effects in person perception were discussed.

PMID- 9551540
TI  - [The effect of self-enhancement expectation on selection of comparisons as a self
      assessment strategy].
AB  - Selection of others for comparison influences the outcome of self-assessment. The
      present study attempted to examine the effect of expectation for self-enhancement
      on strategic selection of comparisons. A questionnaire study was conducted with
      169 undergraduates, who responded to four sets of questions. First, they listed
      ten abilities each for three areas that desired to acquire in high-level, in
      average-level, and undesired to acquire. Then, they evaluated themselves in
      comparison with others on the thirty abilities, and indicated whom they chose as
      comparisons. Finally, perceived probabilities were assessed of acquiring each
      ability. Results showed that selection of superior others was more when evaluated
      abilities were desired to acquire in high-level and perceived probability high
      than otherwise. This suggested that comparison with superior others was made if
      expectation for self-enhancement was high. The expectation therefore affects the
      likelihood of self-assessment behavior, and self-assessment is a necessary
      component of future self-enhancement.

PMID- 9551541
TI  - [Relationship-enhancement and relative self-effacement].
AB  - Two studies investigated the tendency of people to enhance their close
      relationship and to efface oneself in front of their partners. In Study 1, 193
      college students estimated the extent to which their best friendship is better
      than other's best friendship. Overall, they showed a strong tendency of enhancing
      own relationship; they rated their best friendship to be better than the average.
      Within the close relationship, however, they showed self-effacement; they rated
      their best friends, compared with themselves, in more positive way. In Study 2,
      41 husband-wife couples attended as subjects. Again, they showed marital
      relationship-enhancement and relative self-effacement. Furthermore, their
      subjective happiness was mainly explained by own relationship enhancement. These
      results were discussed from several points.

PMID- 9551542
TI  - [The effect of prior information on perception of ongoing behavior of others:
      information processing at the extraction stage].
AB  - This study investigated the effect of prior information on the extraction stage,
      particularly on the amount of behavior extraction, of information processing when
      perceiving ongoing behavior of others. In terms of prior information they
      received, 102 subjects were randomly assigned to three groups: familiarity,
      desirability, and neutral conditions. Twelve video clips, each about 30 seconds
      long, of a male stimulus actor in daily life were made. The theme of each clip
      was one of the three: familiarity, desirability, or activity. The subjects were
      instructed to form an impression of the male actor, and to press a button when
      they saw an impression-relevant action and release it when it was over. Results
      suggested that subjects extracted behavior that was relevant to prior information
      more frequently, and extraction rates were higher for relevant video clips.
      However, impression change was found after the observation-extraction task.
      Hence, it implies that prior information affects the extraction stage, but not
      the judgment stage, of perceiving ongoing behavior of others.

PMID- 9551543
TI  - [Stress-buffering effects of perceived social supports from family members and
      friends: a comparison of college students and middle-aged adults].
AB  - This study investigated perceived social support, emotional as well as
      instrumental, from family members and friends, and examined their stress
      buffering effects on depression in college students and middle-aged adults in
      Japan. For both samples, family members were relatively more important sources of
      instrumental support, whereas friends were primarily perceived as emotional
      support providers. No gender differences were found for the middle-aged adults,
      but as in previous studies, women in the college sample perceived more support
      for them than men. A series of hierarchical regression analyses with support by
      stress interaction terms revealed distinctive patterns of support effects on
      depression for men and women of each sample. Characteristics of perceived social
      support in each sample were described, and overall results suggested that it is
      essential in social support research to take the meanings of supportive
      relationship into consideration, in the context of social and developmental
      factors of the samples under study.

PMID- 9551544
TI  - [The role of similarity and category in confirmation judgement of category-based
      induction: an examination of the similarity-coverage model].
AB  - Induction is called category-based induction if its premises and conclusion are
      of the form "All members of a category C have property P." Osherson, Smith,
      Wilkie, Lopez, and Shafir (1990) advanced similarity-coverage model. But their
      data from a quantitative test of specific induction did not necessarily support
      the model. Three experiments investigate whether their modeling of similarity and
      coverage was not valid or their experiments were not valid. The following results
      were obtained. Coverage did not affect confirmation judgement in premise
      variation type induction which Osherson et al. (1990) dealt with, and coverage
      effect was verified in conclusion-variation type induction which is more everyday
      and needs less processing load. In the latter case, coverage had to be weighted
      by typicality of conclusion in an inclusive category. And when mixed inductions
      were included, confirmation judgement was based not on coverage but on a
      belonging relation to an upper category and similarity between premise categories
      and a conclusion category.

PMID- 9551545
TI  - [On the relationship between recognition memory of items and test-retest effect].
AB  - The main purpose of this paper is to examine the relationship of recognition
      memory of test items to test-retest effect. For this aim, two tests consisting of
      17 items from self-evaluative consciousness scale and 24 dummy items were
      administered to 163 female college students at an interval of one week. Although
      the results showed clear test-retest of type A and B (Hasegawa, 1995b), namely
      the changes in their self-ratings on both positive and negative items toward a
      more adjustive level, the test-retest effect of type II (Hayamizu, 1977), namely
      the increase in internal consistency of subscale, did not appear. The results
      also showed no influence of the rate of item recognition to the test-retest
      effects, leading to a modification of some part of the hypotheses. This result
      suggests that it is implicit memory rather than recognition memory that is
      related to test-retest effect.

PMID- 9551546
TI  - Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine
      phosphatase SHP-2.
AB  - The crystal structure of the protein tyrosine phosphatase SHP-2 reveals the
      mechanism of auto-inhibition of phosphatase activity by its SH2 domains.
      Phosphotyrosine peptide stimulation of the phosphatase activity, resulting from
      peptide binding to the N-terminal SH2 domain, is linked to conformational changes
      within the protein, including an unprecedented allosteric transition of the N
      terminal SH2 domain.

PMID- 9551547
TI  - NO news is good news.
AB  - The recent determination of the crystal structure of microsomal cytochrome P450
      reductase, a diflavin protein that shuttles electrons from NADPH to the P450
      heme, represents a significant advance towards the understanding of cytochromes
      P450. A similar advance was made in a related enzyme system, nitric oxide
      synthase (NOS). The crystal structure of the NOS heme domain reveals a very
      different architecture to that observed in P450s and offers significant insight
      into the production of nitric oxide, one of nature's most important regulatory
      molecules.

PMID- 9551548
TI  - Marrying structure and genomics.

PMID- 9551549
TI  - The Argonne Structural Genomics Workshop: Lamaze class for the birth of a new
      science.

PMID- 9551550
TI  - New aspects of electron transfer revealed by the crystal structure of a truncated
      bovine adrenodoxin, Adx(4-108).
AB  - BACKGROUND: Adrenodoxin (Adx) is a [2Fe-2S] ferredoxin involved in steroid
      hormone biosynthesis in the adrenal gland mitochondrial matrix of mammals. Adx is
      a small soluble protein that transfers electrons from adrenodoxin reductase (AR)
      to different cytochrome P450 isoforms where they are consumed in hydroxylation
      reactions. A crystallographic study of Adx is expected to reveal the structural
      basis for an important electron transfer reaction mediated by a vertebrate [2Fe
      2S] ferredoxin. RESULTS: The crystal structure of a truncated bovine adrenodoxin,
      Adx(4-108), was determined at 1.85 A resolution and refined to a crystallographic
      R value of 0.195. The structure was determined using multiple wavelength
      anomalous dispersion phasing techniques, making use of the iron atoms in the [2Fe
      2S] cluster of the protein. The protein displays the compact (alpha + beta) fold
      typical for [2Fe-2S] ferredoxins. The polypeptide chain is organized into a large
      core domain and a smaller interaction domain which comprises 35 residues,
      including all those previously determined to be involved in binding to AR and
      cytochrome P450. A small interdomain motion is observed as a structural
      difference between the two independent molecules in the asymmetric unit of the
      crystal. Charged residues of Adx(4-108) are clustered to yield a strikingly
      asymmetric electric potential of the protein molecule. CONCLUSIONS: The crystal
      structure of Adx(4-108) provides the first detailed description of a vertebrate
      [2Fe-2S] ferredoxin and serves to explain a large body of biochemical studies in
      terms of a three-dimensional structure. The structure suggests how a change in
      the redox state of the [2Fe-2S] cluster may be coupled to a domain motion of the
      protein. It seems likely that the clearly asymmetric charge distribution on the
      surface of Adx(4-108) and the resulting strong molecular dipole are involved in
      electrostatic steering of the interactions with AR and cytochrome P450.

PMID- 9551551
TI  - Activation of Bacillus licheniformis alpha-amylase through a disorder-->order
      transition of the substrate-binding site mediated by a calcium-sodium-calcium
      metal triad.
AB  - BACKGROUND: The structural basis as to how metals regulate the functional state
      of a protein by altering or stabilizing its conformation has been characterized
      in relatively few cases because the metal-free form of the protein is often
      partially disordered and unsuitable for crystallographic analysis. This is not
      the case, however, for Bacillus licheniformis alpha-amylase (BLA) for which the
      structure of the metal-free form is available. BLA is a hyperthermostable enzyme
      which is widely used in biotechnology, for example in the breakdown of starch or
      as a component of detergents. The determination of the structure of BLA in the
      metal-containing form, together with comparisons to the apo enzyme, will help us
      to understand the way in which metal ions can regulate enzyme activity. RESULTS:
      We report here the crystal structure of native, metal-containing BLA. The
      structure shows that the calcium-binding site which is conserved in all alpha
      amylases forms part of an unprecedented linear triadic metal array, with two
      calcium ions flanking a central sodium ion. A region around the metal triad
      comprising 21 residues exhibits a conformational change involving a helix
      unwinding and a disorder-->order transition compared to the structure of metal
      free BLA. Another calcium ion, not previously observed in alpha-amylases, is
      located at the interface between domains A and C. CONCLUSIONS: We present a
      structural description of a major conformational rearrangement mediated by metal
      ions. The metal induced disorder-->order transition observed in BLA leads to the
      formation of the extended substrate-binding site and explains on a structural
      level the calcium dependency of alpha-amylases. Sequence comparisons indicate
      that the unique Ca-Na-Ca metal triad and the additional calcium ion located
      between domains A and C might be found exclusively in bacterial alpha-amylases
      which show increased thermostability. The information presented here may help in
      the rational design of mutants with enhanced performance in biotechnological
      applications.

PMID- 9551552
TI  - Copper amine oxidase from Hansenula polymorpha: the crystal structure determined
      at 2.4 A resolution reveals the active conformation.
AB  - BACKGROUND: Copper-containing amine oxidases (CAOs) are widespread in nature.
      These enzymes oxidize primary amine substrates to the aldehyde product, reducing
      molecular oxygen to hydrogen peroxide in the process. CAOs contain one type 2
      copper atom and topaquinone (TPQ), a modified tyrosine sidechain utilized as a
      redox cofactor. The methylamine oxidase from the yeast Hansenula polymorpha
      (HPAO) is an isoform of CAO with a preference for small aliphatic amine or
      phenethylamine substrates. The enzyme is dimeric with a subunit molecular weight
      of 78 kDa. Structural studies are directed at understanding the basis for
      cofactor biogenesis and catalytic efficiency. RESULTS: The X-ray crystal
      structure of HPAO has been solved at 2.4 A resolution by a combination of
      molecular replacement and single isomorphous replacement followed by refinement
      using sixfold symmetry averaging. The electron density at the catalytic site
      shows that the TPQ conformation corresponds to that of the active form of the
      enzyme. Two channels, one on either side of TPQ, are observed in the structure
      that provide access between the active site and the bulk solvent. CONCLUSIONS:
      The structure shows TPQ in a position poised for catalysis. This is the first
      active CAO structure to reveal this conformation and may help further our
      understanding of the catalytic mechanism. On the substrate side of TPQ a water
      containing channel leading to the protein surface can serve as an entrance or
      exit for substrate and product. On the opposite side of TPQ there is direct
      access from the bulk solvent of the dimer interface by which molecular oxygen may
      enter and hydrogen peroxide depart. In addition, a network of conserved water
      molecules has been identified which may function in the catalytic mechanism.

PMID- 9551553
TI  - Human theta class glutathione transferase: the crystal structure reveals a
      sulfate-binding pocket within a buried active site.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) comprise a multifunctional group of
      enzymes that play a critical role in the cellular detoxification process. These
      enzymes reduce the reactivity of toxic compounds by catalyzing their conjugation
      with glutathione. As a result of their role in detoxification, GSTs have been
      implicated in the development of cellular resistance to antibiotics, herbicides
      and clinical drugs and their study is therefore of much interest. In mammals, the
      cytosolic GSTs can be divided into five distinct classes termed alpha, mu, pi,
      sigma and theta. The human theta class GST, hGST T2-2, possesses several
      distinctive features compared to GSTs of other classes, including a long C
      terminal extension and a specific sulfatase activity. It was hoped that the
      determination of the structure of hGST T2-2 may help us to understand more about
      this unusual class of enzymes. RESULTS: Here we present the crystal structures of
      hGST T2-2 in the apo form and in complex with the substrates glutathione and 1
      menaphthyl sulfate. The enzyme adopts the canonical GST fold with a 40-residue C
      terminal extension comprising two helices connected by a long loop. The extension
      completely buries the substrate-binding pocket and occludes most of the
      glutathione-binding site. The enzyme has a purpose-built novel sulfate-binding
      site. The crystals were shown to be catalytically active: soaks with 1-menaphthyl
      sulfate result in the production of the glutathione conjugate and cleavage of the
      sulfate group. CONCLUSIONS: hGST T2-2 shares less than 15% sequence identity with
      other GST classes, yet adopts a similar three-dimensional fold. The C-terminal
      extension that blocks the active site is not disordered in either the apo or
      complexed forms of the enzyme, but nevertheless catalysis occurs in the
      crystalline state. A narrow tunnel leading from the active site to the surface
      may provide a pathway for the entry of substrates and the release of products.
      The results suggest a molecular basis for the unique sulfatase activity of this
      GST.

PMID- 9551554
TI  - The structure of the complex of plastocyanin and cytochrome f, determined by
      paramagnetic NMR and restrained rigid-body molecular dynamics.
AB  - BACKGROUND: The reduction of plastocyanin by cytochrome f is part of the chain of
      photosynthetic electron transfer reactions that links photosystems II and I. The
      reaction is rapid and is influenced by charged residues on both proteins.
      Previously determined structures show that the plastocyanin copper and cytochrome
      f haem redox centres are some distance apart from the relevant charged
      sidechains, and until now it was unclear how a transient electrostatic complex
      can be formed that brings the redox centres sufficiently close for a rapid
      reaction. RESULTS: A new approach was used to determine the structure of the
      transient complex between cytochrome f and plastocyanin. Diamagnetic chemical
      shift changes and intermolecular pseudocontact shifts in the NMR spectrum of
      plastocyanin were used as input in restrained rigid-body molecular dynamics
      calculations. An ensemble of ten structures was obtained, in which the root mean
      square deviation of the plastocyanin position relative to cytochrome f is 1.0 A.
      Electrostatic interaction is maintained at the same time as the hydrophobic side
      of plastocyanin makes close contact with the haem area, thus providing a short
      electron transfer pathway (Fe-Cu distance 10.9 A) via residues Tyr1 or Phe4
      (cytochrome f) and the copper ligand His87 (plastocyanin). CONCLUSIONS: The
      combined use of diamagnetic and paramagnetic chemical shift changes makes it
      possible to obtain detailed information about the structure of a transient
      complex of redox proteins. The structure suggests that the electrostatic
      interactions 'guide' the partners into a position that is optimal for electron
      transfer, and which may be stabilised by short-range interactions.

PMID- 9551555
TI  - Adaptation of an enzyme to regulatory function: structure of Bacillus subtilis
      PyrR, a pyr RNA-binding attenuation protein and uracil phosphoribosyltransferase.
AB  - BACKGROUND: The expression of pyrimidine nucleotide biosynthetic (pyr) genes in
      Bacillus subtilis is regulated by transcriptional attenuation. The PyrR
      attenuation protein binds to specific sites in pyr mRNA, allowing the formation
      of downstream terminator structures. UMP and 5-phosphoribosyl-1-pyrophosphate
      (PRPP), a nucleotide metabolite, are co-regulators with PyrR. The smallest RNA
      shown to bind tightly to PyrR is a 28-30 nucleotide stem-loop that contains a
      purine-rich bulge and a putative-GNRA tetraloop. PyrR is also a uracil
      phosphoribosyltransferase (UPRTase), although the relationship between enzymatic
      activity and RNA recognition is unclear, and the UPRTase activity of PyrR is not
      physiologically significant in B. subtilis. Elucidating the role of PyrR
      structural motifs in UMP-dependent RNA binding is an important step towards
      understanding the mechanism of pyr transcriptional attenuation. RESULTS: The 1.6
      A crystal structure of B. subtilis PyrR has been determined by multiwavelength
      anomalous diffraction, using a Sm co-crystal. As expected, the structure of PyrR
      is homologous to those proteins of the large type I PRTase structural family; it
      is most similar to hypoxanthine-guanine-xanthine PRTase (HGXPRTase). The PyrR
      dimer differs from other PRTase dimers, suggesting it may have evolved
      specifically for RNA binding. A large, basic, surface at the dimer interface is
      an obvious RNA-binding site and uracil specificity is probably provided by
      hydrogen bonds from mainchain and sidechain atoms in the hood subdomain. These
      models of RNA and UMP binding are consistent with biological data. CONCLUSIONS:
      The B. subtilis protein PyrR has adapted the substrate- and product-binding
      capacities of a PRTase, probably an HGXPRTase, producing a new regulatory
      function in which the substrate and product are co-regulators of transcription
      termination. The structure is consistent with the idea that PyrR regulatory
      function is independent of catalytic activity, which is likely to be extremely
      low under physiological conditions.

PMID- 9551556
TI  - Structural adaptations of the cold-active citrate synthase from an Antarctic
      bacterium.
AB  - BACKGROUND: The structural basis of adaptation of enzymes to low temperature is
      poorly understood. Dimeric citrate synthase has been used as a model enzyme to
      study the structural basis of thermostability, the structure of the enzyme from
      organisms living in habitats at 55 degrees C and 100 degrees C having previously
      been determined. Here the study is extended to include a citrate synthase from an
      Antarctic bacterium, allowing us to explore the structural basis of cold activity
      and thermostability across the whole temperature range over which life is known
      to exit. RESULTS: We report here the first crystal structure of a cold-active
      enzyme, citrate synthase, isolated from an Antarctic bacterium, at a resolution
      of 2.09 A. In comparison with the same enzyme from a hyperthermophilic host, the
      cold-active enzyme has a much more accessible active site, an unusual
      electrostatic potential distribution and an increased relative flexibility of the
      small domain compared to the large domain. Several other features of the cold
      active enzyme were also identified: reduced subunit interface interactions with
      no intersubunit ion-pair networks; loops of increased length carrying more charge
      and fewer proline residues; an increase in solvent-exposed hydrophobic residues;
      and an increase in intramolecular ion pairs. CONCLUSIONS: Enzymes from organisms
      living at the temperature extremes of life need to avoid hot or cold denaturation
      yet maintain sufficient structural integrity to allow catalytic efficiency. For
      hyperthermophiles, thermal denaturation of the citrate synthase dimer appears to
      be resisted by complex networks of ion pairs at the dimer interface, a feature
      common to other hyperthermophilic proteins. For the cold-active citrate synthase,
      cold denaturation appears to be resisted by an increase in intramolecular ion
      pairs compared to the hyperthermophilic enzyme. Catalytic efficiency of the cold
      active enzyme appears to be achieved by a more accessible active site and by an
      increase in the relative flexibility of the small domain compared to the large
      domain.

PMID- 9551557
TI  - The structure of SAICAR synthase: an enzyme in the de novo pathway of purine
      nucleotide biosynthesis.
AB  - BACKGROUND: The biosynthesis of key metabolic components is of major interest to
      biologists. Studies of de novo purine synthesis are aimed at obtaining a deeper
      understanding of this central pathway and the development of effective
      chemotherapeutic agents. Phosphoribosylaminoimidazolesuccinocarboxamide (SAICAR)
      synthase catalyses the seventh step out of ten in the biosynthesis of purine
      nucleotides. To date, only one structure of an enzyme involved in purine
      biosynthesis has been reported: adenylosuccinate synthetase, which catalyses the
      first committed step in the synthesis of AMP from IMP. RESULTS: We report the
      first three-dimensional structure of a SAICAR synthase, from Saccharomyces
      cerevisiae. It is a monomer with three domains. The first two domains consist of
      antiparallel beta sheets and the third is composed of two alpha helices. There is
      a long deep cleft made up of residues from all three domains. Comparison of
      SAICAR synthases by alignment of their sequences reveals a number of conserved
      residues, mostly located in the cleft. The presence of two sulphate ions bound in
      the cleft, the structure of SAICAR synthase in complex with ATP and a comparison
      of this structure with that of other ATP-dependent proteins point to the
      interdomain cleft as the location of the active site. CONCLUSIONS: The topology
      of the first domain of SAICAR synthase resembles that of the N-terminal domain of
      proteins belonging to the cyclic AMP-dependent protein kinase family. The fold of
      the second domain is similar to that of members of the D-alanine:D-alanine ligase
      family. Together these enzymes form a new superfamily of mononucleotide-binding
      domains. There appears to be no other enzyme, however, which is composed of the
      same combination of three domains, with the individual topologies found in SAICAR
      synthase.

PMID- 9551558
TI  - The structure of the Escherichia coli phosphotransferase IIAmannitol reveals a
      novel fold with two conformations of the active site.
AB  - BACKGROUND: The bacterial phosphoenolpyruvate-dependent phosphotransferase system
      (PTS) catalyses the cellular uptake and subsequent phosphorylation of
      carbohydrates. Moreover, the PTS plays a crucial role in the global regulation of
      various metabolic pathways. The PTS consists of two general proteins, enzyme I
      and the histidine-containing protein (HPr), and the carbohydrate-specific enzyme
      II (EII). EIIs are usually composed of two cytoplasmic domains, IIA and IIB, and
      a transmembrane domain, IIC. The IIA domains catalyse the transfer of a
      phosphoryl group from HPr to IIB, which phosphorylates the transported
      carbohydrate. Knowledge of the structures of the IIA proteins may provide insight
      into the mechanisms by which the PTS couples phosphorylation reactions with
      carbohydrate specificity. RESULTS: We have determined the crystal structure of
      the Escherichia coli mannitol-specific IIA domain, IIAmtl (M(r) 16.3 kDa), by
      multiple anomalous dispersion analysis of a selenomethionine variant of IIAmtl.
      The structure was refined at 1.8 A resolution to an R factor of 19.0% (Rfree
      24.2%). The enzyme consists of a single five-stranded mixed beta sheet, flanked
      by helices on both sides. The phosphorylation site (His65) is located at the end
      of the third beta strand, in a shallow crevice lined with hydrophobic residues.
      The sidechains of two conserved active-site residues, Arg49 and His111, adopt two
      different conformations in the four independent IIAmtl molecules. Using a
      solution structure of phosphorylated HPr, and a combination of molecular
      modelling and NMR binding experiments, structural models of the HPr-IIAmtl
      complex were generated. CONCLUSIONS: The fold of IIAmtl is completely different
      from the structures of other IIA proteins determined so far. The two
      conformations of Arg49 and His111 might represent different states of the active
      site, required for the different phosphoryl transfer reactions in which IIAmtl is
      involved. A comparison of the HPr-IIAmtl model with models of HPr in complex with
      other IIA enzymes shows that the overall interaction mode between the two
      proteins is similar. Differences in the stabilisation of the invariant residue
      Arg17 of HPr by the different IIA proteins might be part of a subtle mechanism to
      control the hierarchy of carbohydrate utilisation by the bacterium.

PMID- 9551559
TI  - The 80S rat liver ribosome at 25 A resolution by electron cryomicroscopy and
      angular reconstitution.
AB  - BACKGROUND: The ribosome is central to protein synthesis in all living organisms.
      Single-particle electron cryomicroscopy has recently led to the determination of
      three-dimensional structures of bacterial ribosomes to approximately 20 A, which
      have since revolutionised our understanding of ribosomal function. The structure
      we present here of the 80S rat liver ribosome leads the way to similar progress
      for mammalian ribosomes. RESULTS: Among the new details revealed by our 25 A
      structure of the 80S rat liver ribosome are channels within the subunits, a large
      'flat ribosomal surface' (FRS) on the outer surface of the large subunit and
      structural extensions of the mammalian compared to the bacterial ribosome. The
      main large subunit channel in both the bacterial and the mammalian species starts
      at the peptidyl transferase centre, below the central protuberance, and ends in
      the FRS, at the lower back of the large subunit. Structurally, the channels of
      both species can be directly superimposed. CONCLUSIONS: The mammalian structural
      extensions--none of which trespass the FRS--can be interpreted in terms of rRNA
      inserts and additional protein content over that of bacterial ribosomes. The main
      large subunit channel, which ends at the FRS, is the best candidate for the exit
      channel for proteins targeted for the endoplasmic reticulum.

PMID- 9551560
TI  - [Postprandial hemodynamic reactions].

PMID- 9551561
TI  - [The characteristics of peptic ulcer in subjects with concomitant ischemic heart
      disease].
AB  - AIM: The study of clinical running of gastric or duodenal ulcer in associated
      coronary heart disease (CHD). MATERIALS AND METHODS: 209 CHD patients with
      gastric ulcer (GU) or duodenal ulcer (DU) were examined clinically plus
      histological examination of gastric or duodenal mucosa biopsies was made.
      RESULTS: In CHD patients GU occurred more frequently (56%) than DU. The lesions
      involved more frequently lesser curvature of the stomach and pyloric part of the
      stomach. Males developed ulcers 3.5 times more frequently than females. Ulcers
      tended to a painless course without season exacerbations. The disease manifested
      first with gastric bleeding in 52% of the patients. GU and DU ran with frequent
      recurrences and long-term exacerbations (76% of patients) which coincided in time
      with CHD exacerbations. 68% of patients developed exacerbations within 10 days
      after myocardial infarction or aortocoronary bypass operation. Helicobacter
      pylori was present as a resolving factor in arising ulcer in 26% of patients.
      Microcirculatory disorders, reduced blood flow speed in gastric or duodenal
      mucosa, hypocoagulation syndrome, dyslipidemia provoked exacerbations in 62% of
      patients. Examinations of biopsies from gastric and duodenal mucosa showed marked
      dystrophic changes in the mucosa, its connective tissue basis in the vessels in
      the presence of mild inflammation at ulcer site. CONCLUSION: The onset of ulcers
      and erosions in the mucosa of the gastrointestinal tract in CHD may be due to
      circulatory disorders in gastric mucosa. The main factors of aggression are
      hypoxia, hypoxia-induced trophic defects in gastric and duodenal mucosa,
      circulatory disorders.

PMID- 9551562
TI  - [The effect of combined treatment using bicycle exercise with a free choice of
      the load parameters on the hemodynamics in peptic ulcer patients].
AB  - AIM: To study the role of bicycle exercise in combined treatment of gastric and
      duodenal ulcer, its effect on central hemodynamics and microcirculation.
      MATERIALS AND METHODS: 94 patients with gastric and duodenal ulcer. 64 patients
      received conventional antiulcer treatment plus exercised on bicycle ergometer in
      free regimen of training. 30 patients on the routine treatment only served as
      control. RESULTS: Doppler echocardiography demonstrated that ulcer patients have
      eukinetic hemodynamic type more frequently. After combined treatment with bicycle
      exercise hyper- and hypokinetic hemodynamic types transformed into the eukinetic
      one, while the eukinetic type remained unchanged. Bicycle exercise contributed to
      normalization of microcirculation (as shown by conjunctival biomicroscopy),
      especially in location of ulcer in the duodenum. CONCLUSION: Introduction of
      bicycle exercise in the treatment of ulcer promoted acceleration of ulcer defects
      healing, especially in patients with hyperkinetic hemodynamics and duodenal
      ulcer.

PMID- 9551563
TI  - [The clinical and morphofunctional characteristics of different types of stomach
      ulcer].
AB  - AIM: The study of a complex of anamnestic, clinicoendoscopic and functional
      morphological characteristics in type I and II (according to Johnson) gastric
      ulcer. MATERIALS AND METHODS: Esophagogastroduodenoscopy, gastric secretion
      tests, determination of blood group and Rh factor were performed in 91 patients
      (52 patients with ulcer type I and 39 with ulcer type II). RESULTS: Ulcers type I
      have arisen in the presence of long-term chronic gastritis. They were associated
      with marked changes in the mucosa of gastric body, its atrophy and intestinal
      metaplasia, persistent recurrences in the same gastric zone. Ulcers type II are
      characterized by hereditary loading, 0(I) blood group, combination with
      gastroduodenal erosions, season occurrence, trend to migration and recurrence in
      different gastric or duodenal zones, HCl hypersecretion, high occurrence of
      Helicobacter pylori infection. CONCLUSION: It is thought valid to include types
      of gastric ulcer in current classification of ulcer.

PMID- 9551564
TI  - [The diagnosis of chronic duodenal obstruction combined with duodenal peptic
      ulcer].
AB  - AIM: The study of clinical manifestations of chronic duodenal ileus (CDI) and
      potential of specific methods of CDI diagnosis in its combination with duodenal
      ulcer (DU). MATERIALS AND METHODS: Assessment of acid-producing gastric function,
      duodenogastric reflux, manometry of the upper gastrointestinal tract,
      fibrogastroduodenoscopy, ultrasonic and x-ray investigations were made in 1140
      patients with chronic DU. RESULTS: 29.2% of the examinees were found to have CDI.
      Specific features of CDI course are described. The diagnostic criteria are
      defined. Higher informative value of the diagnostic methods can be achieved.
      CONCLUSION: The findings can be used in the choice of DU treatment, for
      formulation of indications to duodenocorrective interventions.

PMID- 9551565
TI  - [The prognostic criteria of the course in newly detected duodenal peptic ulcer].
AB  - AIM: Elucidation of the significance of various factors in prognosis of duodenal
      ulcer (DU) severity. MATERIALS AND METHODS: The observational study entered 18
      new cases of DU and 13 healthy controls. All the patients were followed up for 7
      years with annual esophagogastroduodenoscopy. RESULTS: 10 patients (group 1) had
      annual exacerbations of DU, 8 patients had rare exacerbations (group 2). Group 1
      was characterized by basal acid hyperproduction, hyperpepsinogenemia,
      hypergastrinemia, marked contamination with Helicobacter pylori. Patients of
      group 2 had normal basal and pentagastrin-stimulated acid production,
      normopepsinogenemia, normogastrinemia, mild Helicobacter pylori infection.
      CONCLUSION: The 7-year follow-up of new DU cases allowed demonstration of
      functional-morphological prognostic criteria for frequently and rarely recurrent
      DU courses.

PMID- 9551566
TI  - [Gastroesophageal reflux combined with Helicobacter pylori infection].
AB  - AIM: Investigation of the role of Helicobacter pylori infection of the low
      esophagus in patients with duodenal ulcer (DU). MATERIALS AND METHODS: Endoscopic
      examination was performed in 40 DU patients. All the biopsies were examined for
      Helicobacter pylori and degree of relevant contamination. RESULTS: Helicobacter
      pylori was present in all the patients' antral stomachs. It contaminated the low
      part of the esophagus in 17 of 40 patients. Endoscopic changes were more severe
      in those patients who had the infection both in the stomach and in the esophagus.
      CONCLUSION: The presence of Helicobacter pylori in the lower esophagus and antral
      stomach in DU patients may entail negative changes in the stomach and esophagus.

PMID- 9551567
TI  - [Bicarbonate deficiency and duodenal peptic ulcer].
AB  - AIM: The study of alkaline gastric secretion in health and disease and its
      changes in response to blockers of H2-histamine receptors. MATERIALS AND METHODS:
      The trial enrolled 74 patients with duodenal ulcer (DU), 28 patients with chronic
      gastric (CG) and 16 healthy controls. The secretion was studied initially, in
      administration of ranitidine, in stimulation with hydrochloric acid. RESULTS: DU
      patients demonstrated a significant reduction of gastric secretion of
      bicarbonates in the basal and stimulated phases and a 3-fold decrease in the
      proportion alkaline/acid secretion. There was also a trend to acidosis.
      Administration of H2-histamine receptors provided recovery of acid-alkaline
      balance. CONCLUSION: Bicarbonate deficiency is an important element of duodenal
      ulcer pathogenesis.

PMID- 9551568
TI  - [The characteristics of the lipid peroxidation and antioxidant activity of the
      duodenal mucosa in peptic ulcer patients].
AB  - AIM: Lipid peroxidation (LPO) and antioxidant defense (AOD) in ulcer and
      periulcer zones of duodenal mucosa were studied at different phases of ulcer.
      MATERIALS AND METHODS: 111 patients with duodenal ulcer exacerbation before
      treatment and in the course of the treatment were studied versus 23 healthy
      volunteers. RESULTS: In active ulcer there was high activity of LPO and depressed
      AOD. LPO may be initiated by Helicobacter pylori. Pathogenetic measures including
      anti-Helicobacter ones decreased LPO hyperactivity and promoted AOD
      normalization. CONCLUSION: In ulcer, optimal treatment is supposed to combine
      antisecretory and antibacterial drugs adjusted to the activity of ulcer and
      imbalance between LPO and AOD systems in gastric and duodenal mucosa.

PMID- 9551569
TI  - [The results of a morphological study of the gastric and duodenal mucosae in
      patients with vibration-induced disease].
AB  - AIM: Morphological study of gastric and duodenal mucosa in patients with
      vibration disease. MATERIALS AND METHODS: 64 patients with vibration disease
      stage I and II were examined endoscopically, histologically, bacterioscopically
      and morphometrically irrespective of the presence or absence of gastrointestinal
      complaints. RESULTS: Erosive gastroduodenitis, non-erosive gastroduodenitis and
      gastritis, polyps in the stomach and gastric ulcer were diagnosed in 19(29.7%),
      40(62.5%), 2(3.2%) and 1(1.6%) patients, respectively. Small intestinal
      metaplasia occurred in 22% of patients. Helicobacter pylori occurred most
      frequently in the antral part of the stomach (90.24%). Advanced dissemination
      often combined with metaplasia of the small bowel. Morphometrically, there were
      slight differences from relevant values in patients with chronic gastroduodenitis
      who were not exposed to occupational hazards. Vibration disease patients
      exhibited impairment of duodenal vessels (large endothelial nuclei, thick
      arteriolar walls) 2 times more frequently than controls. CONCLUSION: In vibration
      disease, gastric and duodenal mucosa, as a rule, shows signs of chronic
      gastroduodenitis.

PMID- 9551570
TI  - [Chronic viral infection in patients with alcoholic liver involvement].
AB  - AIM: Detection of viral hepatitides markers in patients with alcoholic damage to
      the liver. MATERIALS AND METHODS: Virological, immunological and histochemical
      tests were performed in 36 chronic alcoholics who had enlarged liver and/or
      abnormal hepatic characteristics. RESULTS: 60% of the examinees carried chronic
      HBV, HCV, HDV infection. The activity of chronic inflammation of hepatic
      parenchyma was associated with biological phase of the viral infection
      development. The degree of hepatic parenchyma morphological changes was unrelated
      to the virus type. (HBV, HCV, HDV). CONCLUSION: Alcoholic hepatic damages often
      combine with viral hepatitis.

PMID- 9551571
TI  - [The bile acid and bile lipid spectrum of the migrant population of the Asian
      North with biliary tract diseases].
AB  - AIM: The study of biochemical bile composition in Asian North migrants with
      biliary diseases (BD). MATERIALS AND METHODS: The diagnosis of BD was made upon
      clinical examination, ultrasound scanning, duodenal intubation in 329 examinees.
      The bile was examined for total bile acids, total cholesterol, total
      phospholipids and bile acid spectrum. RESULTS: Cholelithiasis patients were found
      to have high index of bile cholesterol saturation, high level of deoxycholic acid
      and low ratio primary/secondary bile acids. CONCLUSION: Changes in bile lipid
      spectrum are the leading cause of forming bile concrements in migrant population
      of the high altitudes.

PMID- 9551572
TI  - [The indices of lipid metabolism in the blood plasma of patients with chronic
      calculous cholecystitis].
AB  - AIM: The study of lipid fraction spectrum in plasma of patients with chronic
      calculous cholecystitis (CCC) before and after the operative intervention.
      MATERIALS AND METHODS: 28 female patients with CCC. Plasma lipids were measured
      before the operation, 1 and 5 days after it, at the discharge from hospital and
      in healthy donors. RESULTS: Before the operation blood concentrations of total
      lipids, triacylglycerins, phosphatidylcholine and phosphatidylethanolamine were
      elevated. Cholesterol, lisophosphatidylcholine and sphingomyelin,
      cholesterol/phospholipids ratio were subnormal. The same changes of the lipids
      persisted 1 and 5 days after the surgery and at discharge. CONCLUSION: Plasma
      lipids in CCC patients are not corrected early after the surgery and require drug
      correction.

PMID- 9551573
TI  - [Current medical technologies in the treatment of cholelithiasis].
AB  - AIM: Assessment of different approaches to treatment of cholelithiasis (CL).
      MATERIALS AND METHODS: 245 CL patients were given a long-term treatment with
      ursosan, laser lithotripsy and combined modalities. RESULTS: Ursosan promoted
      dissolving of the stones in 56% of the patients. Laser lithotripsy destroyed the
      stones in 74 from 91 patients. Ursosan and laser lithotripsy eliminated the
      concrements in 59 of 67 patients. CONCLUSION: Efficacy of laser lithotripsy in CL
      depends on valid selection of the patients. The combined therapy of CL is
      preferable in patients who reject operative intervention and in those with severe
      somatic complications.

PMID- 9551574
TI  - [Antihypertensive therapy with doxazosin in patients with non-insulin-dependent
      diabetes mellitus].
AB  - AIM: Assessment of the antihypertensive effect of doxazosin, alpha-1 blocker, as
      well as its action on lipid and carbohydrate metabolism, microcirculation and
      platelet function in patients with non-insulin-dependent diabetes mellitus
      (NIDDM). MATERIALS AND METHODS: Doxazosin (tonocardin) treatment was given for 11
      weeks to 33 NIDDM patients with concomitant hypertension. The clinical
      examination comprised evaluation of central hemodynamics, vessels of the fundus
      of eye, lipid and carbohydrate metabolism, renal function, platelet aggregation.
      RESULTS: Tonocardin produced a fall in the systolic blood pressure (BP) by 14%,
      in the diastolic BP--by 17%. The 24-h profile of BP, lipid and purine metabolism,
      microcirculation of the vessels of the fundus of eye also improved. Total
      peripheral vascular resistance, left ventricular myocardial mass and platelet
      aggregation. Carbohydrate metabolism remained unchanged. CONCLUSION: Monotherapy
      with tonocardin (2-8 mg/day) is effective and safe in the treatment of arterial
      hypertension in NIDDM patients.

PMID- 9551575
TI  - [The treatment of peptic ulcer at a polyclinic day hospital].

PMID- 9551576
TI  - [Life support on chronic hemodialysis over the course of 14-15 years (a report of
      2 cases)].

PMID- 9551577
TI  - [Glucagonoma as a tumor found by the therapist].

PMID- 9551578
TI  - [The diagnosis of 3 cases of carcinoid].

PMID- 9551579
TI  - [The efficacy of autofibronectin obtained by heparin cryofractionation in
      patients with trophic ulcerative skin lesions].

PMID- 9551580
TI  - [Prokinetic agents (prokinetics) in the treatment of motor disorders of the
      gastrointestinal tract].

PMID- 9551581
TI  - [The role of helicobacteriosis in stomach and duodenal lesions].

PMID- 9551582
TI  - [Eosinophilic gastroenteritis].

PMID- 9551583
TI  - [Chronic viral diseases of the liver--systemic infections?].

PMID- 9551584
TI  - [Betaxolol (lokren) in arterial hypertension].

PMID- 9551585
TI  - [Imidazoline receptor agonists in the practical treatment of hypertension].

PMID- 9551586
TI  - Introduction. Forces of change in interventional vascular medicine: outlook for
      the next millennium.

PMID- 9551587
TI  - Pathobiologic responses to stenting.
AB  - As the interventions available to treat obstructive coronary artery disease
      become increasingly complex, our understanding of the vascular response to these
      interventions requires greater sophistication. Molecular and cellular biologic
      tools have now propelled us into another phase of work with vascular devices.
      Initially, studies of endovascular implants such as stents focused on developing
      models of vascular injury. With these models, we could then examine the designs
      of individual stents and connect structure with performance. Now we are entering
      a third phase in which stent manufacturers are looking to science to dictate
      stent design.

PMID- 9551588
TI  - In-stent restenosis: the Washington Hospital Center experience.
AB  - In-stent restenosis has become a significant clinical problem. In 1997 alone, it
      is estimated that up to 100,000 patients world-wide with in-stent restenosis were
      treated. Serial intravascular ultrasound (IVUS) analysis has shown that tubular
      slotted stents almost never chronically recoil and that neointimal hyperplasia is
      responsible for in-stent restenosis. With the rapid recent explosion in stent
      use, information about in-stent restenosis has lagged behind, especially on the
      impact of new stent designs. For example, the true prevalence of in-stent
      restenosis (1) varies with the lesion and patient subset, being much higher in
      the "real world" than in the selected patients typically enrolled in many
      studies; and (2) depends on its definition (i.e., clinical vs angiographic,
      intralesion vs in-stent). "Conventional" catheter-based treatments have included
      percutaneous transluminal coronary angioplasty (PTCA), rotational atherectomy,
      excimer laser coronary angioplasty, directional coronary atherectomy, and
      additional stent implantation. Rates of recurrence with these approaches are not
      known and vary considerably among series; however, certain lesions seem likely to
      recur regardless of the treatment modality. Recently, brachytherapy has emerged
      as the most promising way to treat in-stent restenosis.

PMID- 9551589
TI  - Pathophysiology of restenosis: interaction of thrombosis, hyperplasia, and/or
      remodeling.
AB  - In response to arterial injury, a series of intravascular changes take place that
      lead to restenosis: thrombosis, neointimal hyperplasia, and remodeling of the
      vessel. Neointima formation involves thrombosis, recruitment (migration), and
      recruitment/cell proliferation. To determine the source of neointimal cells that
      accumulate at the site of injury, pig models of stented and catheterized arteries
      were examined. The phases of neointima formation can each be seen in the pig in
      which neointimal cells come from nearby arterial tissue. The pig model was also
      employed to assess the effect of different degrees of force exerted by self
      expanding stents on the arterial wall. In this model, the luminal area increased
      in response to chronic stent force. Slow expansion may help prevent neointimal
      hyperplasia and maintain luminal patency without causing damage to the artery.

PMID- 9551590
TI  - Radiation vascular therapy: a novel approach to preventing restenosis.
AB  - In animal studies, beta and gamma radiation delivered via catheter-based systems
      to sites of angioplasty after arterial injury has decreased the neointimal
      proliferation that is a part of the restenotic process. Extending radiotherapy to
      the clinical setting, results of the double-blind, placebo-controlled, randomized
      Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) study
      showed dramatic reductions in the rate of restenosis after coronary stenting when
      catheter-based gamma radiotherapy (with iridium-192) was used. In the Beta Energy
      Restenosis Trial (BERT), angiographic, intravascular ultrasound, and clinical
      outcomes were better than expected with beta brachytherapy. Strontium-90/yttrium
      90 seeds were delivered via a unique catheter system in 35 patients who underwent
      coronary angioplasty. Future trials are being planned to confirm these promising
      results.

PMID- 9551591
TI  - Endovascular brachytherapy: overcoming "practical" obstacles.
AB  - Endovascular radiation therapy has proved to be safe and effective in preventing
      restenosis after coronary intervention both in animal studies and in pilot
      feasibility studies in humans. The rationale for such therapy is that radiation
      prevents neointimal proliferation and vessel constriction after vascular injury.
      Two forms of endovascular radiation therapy are available: catheter-based systems
      and radioactive stenting. However, several practical issues related to this
      technique still need to be addressed, such as questions about dosimetry,
      shielding, expense, handling and disposal of radioisotopes, certification for
      potential users, and-above all-safety and efficacy. In their pivotal studies,
      investigators and industry need to focus on prioritizing the clinical
      applications of this form of treatment. The clinical trials must attempt to
      determine the cost-effectiveness of this therapy as well as its risk versus
      benefit. For example, brachytherapy may prove to be of great benefit to patients
      with in-stent restenosis, and favorable results of studies examining this
      application should expedite the approval of endovascular radiation therapy for
      clinical use.

PMID- 9551593
TI  - Stent grafts for aortic aneurysms: the next interventional challenge.
AB  - Stent grafts (endografts) have proved useful for the endoluminal exclusion of
      peripheral and aortic aneurysms, both those in native arteries and those
      resulting from prior surgery. In addition, their use may apply in some patients
      with occlusive vascular disease. Various types of endografts are being evaluated
      in clinical trials, including those that utilize unsupported grafts with
      stentlike attachment mechanisms and those having a metallic endoskeleton or
      exoskeleton. Relatively complex devices can be delivered through small
      arteriotomies and in some cases percutaneous approaches. Unsupported grafts,
      although more prone to kinking and incomplete expansion, appear to work well.
      Some devices employ modularity, which involves separate placement of
      contralateral limbs and, in some cases, extension devices. For performing
      endovascular grafting, pretreatment planning is critical and requires
      sophisticated imaging, including spiral computed tomography (CT) with 3
      dimensional reconstruction and angiographic evaluation using catheters with
      calibrated markers. Potential advantages of endovascular grafts include a
      decreased hospital stay, a less invasive procedure, and lower morbidity and
      mortality. Several issues remain unresolved and should be addressed by the newer
      generation of these devices.

PMID- 9551592
TI  - Intravascular ultrasound: state of the art and future directions.
AB  - A variety of new devices in the field of intravascular ultrasound imaging are
      being designed and tested. Mechanical intravascular ultrasound (IVUS) devices
      with rotating transducers have been developed that allow transducer pullback with
      integrated longitudinal 2-dimensional displays. Recent advances in the area of
      imaging include (1) solid-state systems that combine ultrasound with balloon and
      stent placement; (2) combined imaging atherectomy devices; (3) imaging cores or
      guidewires; (4) forward-looking devices; (5) 3-dimensional reconstruction
      techniques; (6) high-frequency imaging; and (7) improved methods for
      characterizing tissue. Other promising approaches include magnetic resonance
      imaging, thermography, and optical coherence tomography. An important goal for
      long-term technologic improvement is visualization of lipid accumulations and
      fibrous caps during their early stages of development.

PMID- 9551594
TI  - Current perspectives on direct myocardial revascularization.
AB  - Direct myocardial revascularization (DMR), either surgical or catheter-based,
      uses lasers to create channels between ischemic myocardium and the left
      ventricular cavity to improve perfusion and decrease angina. This technique can
      also be used to deliver drugs to the damaged tissue. Candidates include patients
      with chronic, severe, refractory angina and those unable to undergo conventional
      surgical revascularization or angioplasty because remaining conduits or
      acceptable target vessels are lacking. Although the mechanism of action of DMR is
      still not known, several theories have been proposed, including stimulated
      angiogenesis. Late sequelae also remain to be determined. Channel characteristics
      differ depending on whether they were created by carbon dioxide or
      holmium/yttrium-aluminum-garnet (Ho: YAG) lasers. Catheter-based DMR obviates
      thoracotomy and anesthesia and, in systems that can create electromechanical
      maps, fluoroscopy. Phase I clinical trials are now under way to evaluate catheter
      based DMR, with endpoints that include improvement in symptoms of angina,
      exercise capacity, and radionuclide myocardial perfusion.

PMID- 9551595
TI  - Preferential benefit of platelet glycoprotein IIb/IIIa receptor blockade:
      specific considerations by device and disease state.
AB  - Several patient subgroups appear to benefit preferentially from inhibition of
      platelet glycoprotein (GP) IIb/IIa receptors. In clinical trials the GP IIb/IIa
      blocker abciximab (ReoPro; Lilly) proved both safe and effective in improving
      outcomes after coronary interventions. Endpoints of death, myocardial infarction
      (MI), and need for urgent intervention were significantly decreased in a
      randomized placebo-controlled trial of patients treated with abciximab in
      conjunction with either low-dose or standard-dose weight-adjusted heparin during
      elective percutaneous coronary revascularization. In addition, studies have shown
      that patients undergoing unplanned stent deployment or ablative technologies
      benefit from GP IIb/IIa blockade. Patients undergoing saphenous vein graft
      intervention also derive specific benefits. These agent--specifically abciximab,
      eptifibatide (INTEGRILIN; Cor/Schering), and tirofiban--have also benefited
      patients with the acute coronary syndromes (e.g., unstable angina) by decreasing
      ischemic events.

PMID- 9551597
TI  - Virus-cell interactions. Introduction.

PMID- 9551596
TI  - Lipid-lowering therapy after coronary revascularization: the interventional
      cardiologist's perspective.
AB  - Despite the success of coronary interventions in the treatment of stenosis due to
      coronary atherosclerosis, it behooves cardiologists to treat the underlying
      disease by decreasing patients' cholesterol levels. Intravascular ultrasound has
      made it possible to detect plaque accumulation not visible on angiography.
      Although advanced lesions that are fibrous and calcific can be treated with
      atherectomy and lasers, it is the soft, lipid-laden plaque that is particularly
      vulnerable to rupture and leads to coronary events. Therefore, attention must
      also focus on decreasing atherosclerotic progression in patients who have
      undergone coronary interventions. Studies have clearly shown the value of
      cholesterol reduction in decreasing coronary events. However, a review of
      cardiologists' practices shows that more aggressive lipid-lowering therapy is
      needed. One way to achieve this goal is to treat and monitor patients who have
      undergone revascularization procedures and to encourage patients to become more
      involved in their own care.

PMID- 9551598
TI  - Cell cycle analysis of retroviral vector gene expression during early infection.
AB  - To examine the pattern of retroviral vector gene expression during early stages
      of infection, a Moloney murine leukemia virus (M-MuLV)-based vector that
      transcribes the simian virus 40 (SV40) large T antigen (Tag) gene from the viral
      long terminal repeat (LTR) was used to infect proliferating rodent fibroblasts.
      At various times after infection, cells were fixed and stained for Tag by
      indirect immunofluorescence, and for DNA using propidium iodide. Tag
      immunofluorescence and DNA content were both quantified by flow cytometry. The
      results showed that Tag expression was first detected exclusively in the late G1
      and early S phases of the cell cycle, approximately 12 h postinfection. The
      infection was synchronous in that Tag-expressing cells detected at 12 h, in late
      G1 and early S, moved as a discrete population through S phase, into the G2 + M
      phases of the cell cycle and then back into G1 during the next 8-10 h. The
      presence of a synchronous Tag-expressing cell population suggests that, at time
      of infection, cells in certain phases of the cell cycle were more susceptible to
      infection than cells in other phases. This may be related to synchronizing events
      that must occur before viral genes are expressed in infected cells; one such
      event may be integration of viral DNA into cellular chromosomes (i.e., provirus
      formation) that requires cells to pass through an M phase.

PMID- 9551599
TI  - Identification of SV40 T-antigen mutants that alter T-antigen-induced chromosome
      damage in human fibroblasts.
AB  - The SV40 T antigen causes numerical (aneuploidy) and structural (aberrations)
      chromosome damage when expressed in human diploid fibroblasts. This chromosome
      damage precedes the acquisition of neoplastic traits such as anchorage
      independence, colony formation in reduced serum growth factors, immortalization,
      or tumorigenicity. Therefore, chromosome damage may be important in acquiring
      these traits because it could provide a mutational mechanism. To determine how
      the T antigen causes chromosome damage, point mutations were constructed that
      altered previously defined biochemical functions of the T protein. Mutant T
      antigen constructs were introduced into human diploid fibroblasts and selected by
      using G418. Clones of G418r cells that expressed mutant T antigens were expanded
      and scored for chromosome damage. Most of these mutant T antigens caused
      [corrected] levels of chromosome damage similar to those caused by [corrected]
      the wild-type T antigen. However, some T-antigen mutants induced fewer chromosome
      changes. A subset of these clones that induced less chromosome damage than wild
      type T were examined further. Mutant T-antigen protein levels from this subset
      were quantified with flow cytometry and compared with wild-type protein
      expression levels. Mutations of T antigen shown previously to form less stable
      complexes with p53 caused less chromosome damage. A mutation in the zinc finger
      domain of T antigen also caused less chromosome damage. Interestingly, a mutant
      that caused loss of the ATPase activity of T antigen caused an increase in
      endoreduplicated cells. Also, a correlation was noted between cells expressing
      very low levels of T antigen (below detection limits when using flow cytometry)
      and an undamaged karyotype. This correlation indicates that there is a threshold
      level of T-antigen expression that induces chromosome damage and that expression
      levels on a per-cell basis rather than on a population basis should be considered
      in subsequent studies.

PMID- 9551600
TI  - Activities of SV40 T antigen necessary for the induction of tetraploid DNA
      content in permissive CV-1 cells.
AB  - To determine the role of SV40 T antigen in stimulating multiple rounds of DNA
      synthesis in permissive cells, CV-1 cells were transfected with plasmids
      expressing mutant or wt T antigen in the presence or absence of the SV40 origin
      of replication. Induction of cells with > G2 DNA content (tetraploid DNA content)
      and levels of T antigen protein were detected and analyzed by flow cytometry. The
      mutant T antigen proteins demonstrated the expected phenotypes as determined by
      immunoprecipitation. Elevated levels of T antigen protein were detected in each
      transfection, but full-length T antigen alone was responsible for the tetraploid
      DNA content. The studies show that full-length T antigen with point mutations to
      reduce binding to the cellular proteins p53 and/or Rb were capable of inducing >
      G2 DNA content though the induction by these mutants was greatly enhanced by the
      presence of the SV40 origin of replication. Truncated T antigen (aa 1-259) could
      induce cells with tetraploid DNA content only in the presence of the SV40 origin
      of replication and the absence of Rb binding. These studies suggest that multiple
      functions of T antigen are involved in the stimulation of the second round of
      cellular DNA synthesis.

PMID- 9551601
TI  - Okadaic acid induces appearance of the mitotic epitope MPM-2 in SV40-infected CV
      1 cells with a >G2-phase DNA content.
AB  - Simian virus 40 (SV40) infection of quiescent monkey kidney cells stimulates two
      successive rounds of cellular DNA synthesis without an intervening mitosis. This
      uncoupling of S phase and mitosis indicates that SV40 modulates pathways
      regulating the G2-to-M phase transition. To examine the integrity of mitotic
      initiation pathways in infected cells that have bypassed mitosis, SV40-infected
      CV-1 cells were treated with okadaic acid (OA), a known inducer of premature
      mitosis in other cell types. OA treatment triggered the appearance of the mitotic
      marker MPM-2 in SV40-infected CV-1 cells progressing through either the first
      (diploid) or second (tetraploid) S phases. These results demonstrate that a
      subset of mitotic pathways are intact but inactive in SV40-infected cells that
      have bypassed mitosis and initiated tetraploid S phase.

PMID- 9551602
TI  - Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive
      patients by simultaneous flow cytometric analysis of intracellular HIV RNA and
      cellular immunophenotype.
AB  - Determinations of plasma HIV viral RNA copy numbers help to define the kinetics
      of HIV-1 infection in vivo and to monitor antiretroviral therapy. However,
      questions remain regarding the identity of various infected cell types
      contributing to this free virus pool and to the in vivo lifecycle of HIV during
      disease progression. Characterization of a novel fluorescence in situ
      hybridization (FISH) assay employing a pool of labeled oligonucleotide probes
      directed against HIV RNA was done followed by coupling of the FISH assay with
      simultaneous surface immunophenotyping to address these questions. In vitro
      characterizations of this assay using tumor necrosis factor-alpha stimulated and
      unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive
      cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood
      mononuclear cells from 39 HIV-seropositive patients on no, single, combination,
      or triple drug therapy and 8 HIV-seronegative patients were examined. The
      majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA
      and a significantly higher fraction of patients with high plasma viral load
      carried positive monocytes (13/16) than did patients in the low plasma viral load
      group (11/23). These results demonstrate the effectiveness of a novel FISH assay
      for identifying and monitoring HIV-infected cell populations in the peripheral
      blood of HIV-positive patients. In addition, monocytes are a major source of
      cellular HIV virus in the peripheral blood of HIV patients, even with progression
      of disease.

PMID- 9551604
TI  - Automated image analysis system for detecting boundaries of live prostate cancer
      cells.
AB  - Image analysis provides a powerful tool for quantifying cell motility and has
      been used to correlate motility with metastatic potential in an animal model of
      prostate cancer. However, widespread use of this image analysis method has been
      limited because earlier methods of quantitative analysis required time-intensive
      and subjective manual tracing of cell contours. In this report, we describe a
      fully automated image segmentation algorithm for detection and morphometric
      description of prostatic cells. The segmentation system was tested on prostate
      cell images generated from Hoffman modulation contrast microscopy (47 cells at 64
      time points = 3,008 images) and differential interference contrast microscopy (29
      cells at 64 times points plus 1 cell at 62 time points = 1,918 images).
      Morphometric measurements were derived from computer-determined cell boundaries
      and compared with the same measurements derived from manually traced cell
      boundaries. Final correlation coefficients for area and perimeter measurements
      for Hoffman and differential interference contrast microscopy were (0.76, 0.62)
      and (0.93, 0.93), respectively. Results with our differential interference
      contrast images demonstrate that our segmentation algorithm reliably and
      efficiently replaces the need for manually traced cell boundaries in addition to
      eliminating intraobserver variation. Our automated segmentation process will have
      immediate utility in our motility analysis system that relates cell motility with
      metastatic potential of prostate cancer.

PMID- 9551603
TI  - Efficient, interactive, and three-dimensional segmentation of cell nuclei in
      thick tissue sections.
AB  - Segmentation of intact cell nuclei in three-dimensional (3D) images of thick
      tissue sections is an important basic capability necessary for many biological
      research studies. Because automatic algorithms do not correctly segment all
      nuclei in tissue sections, interactive algorithms may be preferable for some
      applications. Existing interactive segmentation algorithms require the analyst to
      draw a border around the nucleus under consideration in all successive two
      dimensional (2D) planes of the 3D image. The present paper describes an algorithm
      with two main advantages over the existing method. First, the analyst draws
      borders only in 2D planes that cut approximately through the center of the
      nucleus under consideration so that the nuclear borders generally are most
      distinct. Second, the analyst draws only five borders around each nucleus, and
      then the algorithm interpolates the entire surface. The algorithm results in
      segmented objects that correspond to individual, visually identifiable nuclei.
      The segmented surfaces, however, may not exactly represent the true nuclear
      surface. An optional, automatic surface optimization algorithm can be applied to
      reduce this error.

PMID- 9551605
TI  - Colcemid-induced apoptosis of cultured human glioma: electron microscopic and
      confocal laser microscopic observation of cells sorted in different phases of
      cell cycle.
AB  - The effect of the antitubulin agent colcemid on human glioma cells was
      investigated by sorting cells with different DNA content and subjecting them to
      confocal laser microscopy and transmission electron microscopy. The human glioma
      cell line U251MG was exposed to colcemid at a concentration of 0.05 microg for 16
      h. Flow cytometric analysis revealed the accumulation of cells in S/G2M phase.
      Cells harvested from each of G0/G1 and S/G2M peaks were then analyzed by confocal
      laser microscopy and transmission electron microscopy. Confocal laser microscopy
      revealed that colcemid-treated cells harvested from the G0/G1 peak contained
      mitotic and apoptotic cells in addition to interphase cells. Electron microscopy
      confirmed that colcemid-treated cells in the G0/G1 peak had fragmented nuclei
      typical of apoptotic cells and mitotic cells with altered chromatin structure.
      Some mitotic cells obtained by mitotic shake-off after treatment with colcemid
      showed DNA strand breaks defined by in situ nick end labeling. The present study
      indicates that mitotic as well as interphase apoptosis occurs in U251MG cells
      following colcemid treatment.

PMID- 9551606
TI  - Flow cytometric measurement of benzo[a]pyrene-diol-epoxide-DNA adducts in normal
      human peripheral lymphocytes and cultured human lung cancer cells.
AB  - DNA adducts are mainly detected by 32P-postlabeling and enzyme-linked
      immunosorbent assays. We have established a method for detection of
      benzo[a]pyrene-diol-epoxide (BPDE)-DNA adducts by flow cytometry, and have
      clarified the effects of the DNA adducts on cell-cycle progression and the
      relationship between cell-cycle phases and DNA adduct formation, using human
      peripheral lymphocytes and three human lung cancer cell lines. We measured the
      BPDE-DNA adduct levels in both lymphocytes and cancer cells by isolating nuclei,
      using a nuclear isolation buffer containing Triton X-100 and staining with a BPDE
      DNA-specific monoclonal antibody and biotin-streptavidin fluorescein conjugates.
      BPDE did not affect cell-cycle progression in human peripheral lymphocytes.
      However, in human lung cancer cells exposed to > 1 microg/ml BPDE, accumulation
      of cells in the S phase was seen. Cells with DNA content greater than G2M
      (aneuploid cells) or cells with less than G1 DNA content (apoptotic cells)
      increased gradually with exposure to increasing BPDE concentrations, suggesting
      that BPDE may affect cell-cycle progression through binding to DNA. Thus, the
      measurement of DNA adducts by flow cytometry may provide new insights into
      carcinogenesis.

PMID- 9551607
TI  - Flow cytometric assessment of cell structural and functional changes induced by
      acetic acid in the yeasts Zygosaccharomyces bailii and Saccharomyces cerevisiae.
AB  - Flow cytometry (FCM) was used with different viability dyes to assess changes in
      cell structure and function induced by acetic acid (AA) in populations of
      Zygosaccharomyces bailii (AA resistant) and Saccharomyces cerevisiae (AA
      sensitive). Kinetic changes in esterase activity, intracellular dye processing,
      and membrane integrity were monitored, and to detect those changes we used three
      assays involving fluorescein diacetate hydrolysis, FUN-1 processing, and
      propidium iodide exclusion, respectively. In S. cerevisiae, the decrease in the
      ability to process FUN-1 preceded the decrease in esterase activity, and there
      was loss of cell membrane integrity after incubation with AA. In Z. bailii, with
      higher AA concentrations, there was a similar decrease in the ability to process
      FUN-1, which also preceded the loss of cell membrane integrity. Changes in
      esterase activity in this yeast induced by AA treatment could not be monitored
      because the changes occurred independently of the presence of the acid. For
      control samples (untreated cells killed with 10% v/v of AA), the percentages of
      nonaltered cells as estimated by FCM and percentages of viable cells as estimated
      by colony forming unit (CFU) counts were identical. However, for cell samples
      treated for short periods with 3% (v/v) or less of AA, none of the dyes produced
      FCM results comparable to those produced by CFU counts.

PMID- 9551608
TI  - Simian virus 40 as a vector for gene transfer to hematopoietic cells.

PMID- 9551609
TI  - In vitro selection for K562 cells with higher retrovirally mediated copy number
      of aldehyde dehydrogenase class-1 and higher resistance to 4
      hydroperoxycyclophosphamide.
AB  - Previously, we have reported the successful expression of human aldehyde
      dehydrogenase class-1 (ALDH-1) in K562 leukemia cells using a retroviral vector
      and demonstrated low expression that resulted in up to three-fold increase in
      resistance to 4-hydroperoxycyclophosphamide (4-HC), an active derivative to
      cyclophosphamide. The purpose of this study was to investigate whether in vitro
      treatment with 4-HC will allow selection of K562 cells expressing higher levels
      of ALDH-1, and whether these selected cells are more resistant to 4-HC. Stably
      transfected or transduced K562 cells with retroviral pLXSN vector containing ALDH
      1 cDNA (ALDH-1 cells) were treated repeatedly with 4-HC and then allowed to grow
      to confluence in liquid culture. Subsequently, the resistance to 4-HC of ALDH-1
      cells treated once (ALDH-1+) or twice (ALDH-1++) with 4-HC was compared to ALDH-1
      cells or wild-type K562 cells (WT cells). The results show significant increase
      in 4-HC resistance of ALDH-1+ (2- to 16-fold, p < 0.005) over ALDH-1 or WT cells.
      No difference was detected between ALDH-1+ and ALDH-1++. In addition, higher ALDH
      1 mRNA and enzyme activity were found in ALDH-1+ compared to ALDH-1 cells.
      Southern analysis of DNA extracted from the different experimental groups
      demonstrated an eight-fold increase in ALDH-1 cDNA in ALDH-1+ versus the ALDH-1
      cells. This was confirmed by sequential FISH analysis using biotin labeled
      pLXSN/ALDH-1 vector. Positive signals consistently localized to the centromeric
      region of chromosome 9 and the long arm of chromosome 17 were demonstrated only
      in the ALDH-1+ cells and represented a fusion product of multiple copies of the
      pLXSN/ALDH-1 vector. In summary, we have demonstrated that in vitro treatment
      with 4-HC results in the selection of K562 cells with multiple copies of ALDH-1
      gene that are clustered in two main integration sites. These cells demonstrate
      significantly higher resistance to 4-HC when compared to previously untreated
      cells. Such successful in vitro selection could have significant implications for
      future cancer gene therapy protocols.

PMID- 9551610
TI  - Inhibition of human immunodeficiency virus type 1 replication by nuclear chimeric
      anti-HIV ribozymes in a human T lymphoblastoid cell line.
AB  - Human immunodeficiency virus (HIV) infection represents one of the most
      challenging systems for gene therapy. Thanks to the extended knowledge of the
      molecular biology of the HIV life cycle, many different strategies have been
      developed including transdominant modifications of HIV proteins, RNA decoys,
      antisense RNA, ribozymes, and intracellular antibody fragments. In this paper, we
      have tested in a human T lymphoblastoid cell line the antiviral activity of
      ribozymes specifically designed to co-localize inside the nucleus with the Rev
      pre-mRNA before it is spliced and transported to the cytoplasm. This result was
      obtained by inserting the ribozyme in the spliceosomal U1 small nuclear RNA
      (snRNA) and in a derivative that has perfect complementarity with the 5' splice
      site of the Rev pre-mRNA. These ribozymes were tested in human T cell clones and
      were shown to be very efficient in inhibiting viral replication. Not only were
      the p24 levels in the culture medium drastically reduced but so were the
      intracellular HIV transcripts. Control disabled ribozymes enabled us to show the
      specificity of the ribozyme activity. Therefore, these constructs have potential
      utility for gene therapy of HIV-1 infection.

PMID- 9551611
TI  - High-level dystrophin expression after adenovirus-mediated dystrophin minigene
      transfer to skeletal muscle of dystrophic dogs: prolongation of expression with
      immunosuppression.
AB  - Replication-deficient adenovirus vectors (AdV) have been successfully used to
      transfer a truncated human dystrophin cDNA to skeletal muscle of dystrophin
      deficient mdx mice. A dystrophin-deficient golden retriever dog model (GRMD) has
      been identified, which, unlike the mouse model, leads to a clinicopathological
      phenotype similar to that of Duchenne muscular dystrophy (DMD). We show for the
      first time that high-level dystrophin expression in skeletal muscle of GRMD dogs
      can be achieved by AdV-mediated gene transfer. However, a humoral and cellular
      immune response of the host against antigens of viral and transgene origin
      (similar to that occurring in mdx mice after AdV-mediated dystrophin gene
      transfer) leads to a decline of dystrophin expression over a 2-month period.
      Immunosuppression by cyclosporin significantly prolonged transgene expression.
      The GRMD model may help to solve the open questions pertaining to dystrophin gene
      transfer such as systemic delivery and improvement of muscle function before
      human trials for gene replacement therapy in DMD may be considered.

PMID- 9551612
TI  - Vector-specific complementation profiles of two independent primary defects in
      cystic fibrosis airways.
AB  - Cystic fibrosis (CF) lung disease has been linked to multiple primary defects in
      airway epithelia caused by a dysfunctional cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. These defects include altered Cl- and Na+
      permeability as well as intracellular defects in glycoprotein processing. This
      apparent diversity in CFTR function is reflected in the complex patterning of
      CFTR expression in airway epithelia. Such complexities present challenges in the
      design of CF gene therapies that are capable of reconstituting the endogenous
      patterns of CFTR gene expression in appropriate target cells. Using a human
      bronchial xenograft model of the CF airway, we have evaluated the efficacy of
      recombinant adenoviral and cationic liposome-mediated gene transfer to correct Cl
      permeability and mucous sulfation defects found in CF lung disease. Results from
      these studies demonstrated a clear vector-specific complementation profile for
      these two defects that was dependent on the type of cell transduced and the level
      of transgene expression. Single-dose administration of recombinant adenovirus
      effectively transduced high levels of CFTR transgene expression in 11 +/- 1% of
      epithelial cells and was capable of correcting cAMP-induced changes in Cl-
      permeability to 91 +/- 14% that seen in non-CF airways. However, this level of
      transgene expression was incapable of reversing defects in mucous sulfation due
      to the lack of efficient targeting to goblet cells. In contrast, cationic
      liposome-mediated delivery of CFTR encoding plasmids to CF airways achieved
      extremely low levels of transgene expression with insignificant correction (7.4
      +/- 2.4%) of cAMP-induced Cl- permeability. This low level of transgene
      expression, however, efficiently reduced mucous sulfation to levels seen in non
      CF airways. Differences in the complementation profiles of these two vectors in
      correcting Cl- permeability and mucous sulfation defects mirror the ability of
      recombinant adenovirus and liposomes to reconstitute only certain features of the
      endogenous distribution and abundance of CFTR protein expression. Such findings
      suggest that the level of intracellular CFTR required to facilitate proper
      glycoprotein processing may be much lower than that needed to mediate bulk Cl-
      flow across the airway epithelium. In summary, these data present the first
      example by which two different vector systems can efficiently complement
      independent primary defects associated with a single dysfunctional gene.

PMID- 9551613
TI  - Efficient transduction of human hematopoietic cells with the human multidrug
      resistance gene 1 via SV40 pseudovirions.
AB  - Transduction of MDR1 may be of use in chemoprotection of normal bone marrow (BM)
      cells during treatment of malignancies, or as a selectable marker for the
      transfer of other genes into the BM, a critical target for the cure of many
      diseases. To that aim, the human multidrug resistance gene MDR1 was cloned into
      an SV40 pseudoviral vector containing the SV40 origin of replication (ori) and
      encapsidation signal (ses), and the plasmid was encapsidated in COS cells as
      SV40/MDR1 pseudovirions. Expression of the human MDR1 gene was demonstrated in
      murine MEL cells infected with SV40/MDR1 pseudovirions, using a monoclonal
      antibody (MPK16) specific for the human 170-kD P-glycoprotein. Functional P
      glycoprotein was demonstrated by resistance to colchicine in NIH-3T3 cells
      infected with SV40/MDR1 pseudovirions. Activity of P-glycoprotein was assayed by
      rhodamine-123 dye exclusion and fluorescence-activated cell sorter analysis
      (FACS) in various cell types including hematopoietic cells. Highly efficient gene
      transfer and expression was demonstrated in all murine and human cell types
      tested, including primary human BM cells. Using multiplicities of infection (moi)
      of 1-2, over 95% of cells were found to become MDR1+. The percent of MDR1+ cells
      was proportional to the moi. We conclude that the SV40 pseudoviral vector is
      efficient for gene transmission into human hematopoietic cells.

PMID- 9551614
TI  - Systemic effect of human growth hormone after intramuscular injection of a single
      dose of a muscle-specific gene medicine.
AB  - A muscle-specific gene medicine is described that provides for long-term
      secretion of biologically active human growth hormone (hGH) from skeletal muscle
      into the systemic circulation. The hGH gene medicine is composed of a muscle
      specific hGH plasmid expression system complexed with a protective, interactive,
      non-condensing (PINC) delivery system. The muscle-specific gene expression
      system, pSK-hGH-GH, was constructed by linking the promoter/enhancer regions of
      chicken skeletal alpha-actin to hGH gene. C2C12 myoblast transfection with pSK
      hGH-GH resulted in the synthesis of hGH in a muscle-specific manner. Direct
      injection into rat tibialis cranialis muscle of pSK-hGH-GH complexed with a
      polymeric PINC delivery system, polyvinylpyrrolidone (PVP), produced hGH levels
      in muscle that were 10- to 15-fold higher compared with plasmid formulated in
      saline at 14 days post-injection. Intratracheal instillation in rat lung of pSK
      hGH-GH did not produce significantly detectable levels of hGH. In
      hypophysectomized rats, a single intramuscular dose of the pSK-hGH-GH/PVP complex
      resulted in hGH expression and a subsequent increase in serum levels of rat IGF-I
      and growth. hGH expression and effects on rat serum IGF-I levels were detectable
      up to 28 days after injection of formulated plasmid and effects on growth were
      detectable unto 21 days. Anti-hGH antibodies were detectable in serum at 14 days
      post-injection, reached a plateau at 21 days, and remained elevated through the
      study period. Cyclosporin treatment of the pSK-hGH-GH/PVP-injected animals
      completely inhibited the antibody response and resulted in increased hGH
      expression.

PMID- 9551615
TI  - Selective gene transfer into the liver of non-human primates with E1-deleted, E2A
      defective, or E1-E4 deleted recombinant adenoviruses.
AB  - Preclinical studies were designed to investigate the feasibility and safety of
      recombinant adenoviruses transduced into the hepatic artery of nonhuman primates.
      The vectors used are recombinant adenoviruses deleted in E1 and contain either a
      temperature-sensitive mutation in the E2a gene, which encodes a defective DNA
      binding protein at nonpermissive temperatures, or a deletion of the E4 region,
      including open reading frame (ORF) 6. Six 8- to 10-kg baboons underwent femoral
      artery cannulation, and angiographic techniques were used to introduce vector
      selectively into either a portion of the right lobe of the liver via a branch of
      the right hepatic artery or the common hepatic artery. Necropsies were performed
      at 4, 29, or 61 days. Serial sequential liver biopsies were performed in the
      baboons that survived 29 or 61 days. In the 2 baboons with vector transduction
      into the right hepatic artery, X-Gal histochemical analysis of the liver showed
      evidence of quantitatively increased gene transfer in the targeted lobe; however,
      gene transfer was present throughout the liver. Quantitative analysis of
      histopathology showed that portal inflammation was present throughout both livers
      transduced with the highest dose of vector. No differences were seen in the level
      of portal inflammation in targeted and untargeted lobes despite the observed
      qualitative and quantitative differences in gene expression. Southern blot
      analysis of total cellular DNA isolated from targeted and nontargeted lobes
      showed similar levels of viral DNA throughout the liver. Polymerase chain
      reaction (PCR) analysis was able to detect viral DNA sequence in gonads and brain
      as well as many other tissues in baboons treated with high-dose vector. In
      baboons treated with lower doses of an E1-E4 deleted vector expressing the human
      ornithine transcarbamylase (OTC) gene, DNA was detectable by nested PCR in liver
      but not gonads at days 29 and 61. The data suggest that intraarterial
      administration of recombinant adenoviral E1-E4 deleted vector is feasible and
      safe. At high doses of vector, widespread dissemination of vector DNA is seen. At
      low doses, hepatic gene transfer is not associated with vector DNA dissemination
      to gonads.

PMID- 9551616
TI  - Recombinant E1-deleted adenovirus-mediated gene therapy for cancer: efficacy
      studies with p53 tumor suppressor gene and liver histology in tumor xenograft
      models.
AB  - Type 5 adenoviral (Ad) vectors have been the "vector-of-choice" for preclinical
      studies on p53 tumor suppressor gene therapy of cancer. Previous studies have
      examined the in vivo efficacy of p53 Ad when given intratumorally. However
      published information does little to guide clinicians in the design of
      intraperitoneal (i.p.) dosing trials for i.p. tumors, e.g., ovarian, or clinical
      trials using regional organ perfusion, e.g., for lung tumors. Therefore, we
      examined several parameters with special significance for these routes of
      administration. Lung metastases from p53mut MDA-MB-231 mammary xenografts were
      treated with therapeutic levels of intravenous buffer, beta-galactosidase (beta
      Gal) Ad, or p53 Ad. Treatment with intravenous p53 Ad significantly reduced the
      number of metastases per lung and there was a dramatic reduction in the surface
      area occupied by these tumors as compared to control groups. Two types of i.p.
      tumor xenografts were used for preclinical modeling of i.p. gene therapy, the
      p53null SK-OV-3 ovarian and the p53mut DU-145 prostate human cancers. In a study
      examining the effect of different vehicle volumes on the efficacy of a constant
      drug dose, all mice treated with p53 Ad had reduced tumor burden compared to
      controls. Dosing volumes between 0.2 and 1 ml were equally effective and all were
      more effective than a dosing volume of 0.1 ml. However, reduced efficacy was
      observed when a volume of 1.5 ml was used. When the effect of dosing frequency on
      antitumor efficacy was examined, fractionated doses of p53 Ad had somewhat
      greater efficacy than fewer, bolus injections. One of the significant elements in
      the emerging toxicology associated with recombinant adenoviruses is the
      hepatocyte pathology caused by high systemic concentrations of adenovirus. For
      recombinant Ad used in this study, there was a pronounced dose-dependence for the
      liver response, with very high, repeated doses causing significant hepatocellular
      insult. Expression of cytoplasmic beta-Gal protein coincided with areas of
      greatest damage in mice treated with high doses of beta-Gal Ad. Ultrastructural
      examination of hepatocyte intranuclear inclusions revealed moderately electron
      dense, tightly packed granular material interspersed with more electron-dense
      nuclear material. Human tumor xenografts, but not mouse tissues, expressed viral
      hexon protein. In summary, hepatic toxicity caused by high concentrations of
      recombinant adenovirus was observed in murine cancer models. However, therapeutic
      levels of p53 Ad could be achieved which had dramatic efficacy without
      significant pathology.

PMID- 9551617
TI  - Factors influencing recombinant adeno-associated virus production.
AB  - Recombinant adeno-associated virus (rAAV) is produced by transfecting cells with
      two constructs: the rAAV vector plasmid and the rep-cap plasmid. After subsequent
      adenoviral infection, needed for rAAV replication and assembly, the virus is
      purified from total cell lysates through CsCl gradients. Because this is a long
      and complex procedure, the precise titration of rAAV stocks, as well as the
      measure of the level of contamination with adenovirus and rep-positive AAV, are
      essential to evaluate the transduction efficiency of these vectors in vitro and
      in vivo. Our vector core is in charge of producing rAAV for outside investigators
      as part of a national network promoted by the Association Francaise contre les
      Myopathies/Genethon. We report here the characterization of 18 large-scale rAAV
      stocks produced during the past year. Three major improvements were introduced
      and combined in the rAAV production procedure: (i) the titration and
      characterization of rAAV stocks using a stable rep-cap HeLa cell line in a
      modified Replication Center Assay (RCA); (ii) the use of different rep-cap
      constructs to provide AAV regulatory and structural proteins; (iii) the use of an
      adenoviral plasmid to provide helper functions needed for rAAV replication and
      assembly. Our results indicate that: (i) rAAV yields ranged between 10(11) to 5 x
      10(12) total particles; (ii) the physical particle to infectious particle
      (measured by RCA) ratios were consistently below 50 when using a rep-cap plasmid
      harboring an ITR-deleted AAV genome; the physical particle to transducing
      particle ratios ranged between 400 and 600; (iii) the use of an adenoviral
      plasmid instead of an infectious virion did not affect the particles or the
      infectious particles yields nor the above ratio. Most of large-scale rAAV stocks
      (7/9) produced using this plasmid were free of detectable infectious adenovirus
      as determined by RCA; (iv) all the rAAV stocks were contaminated with rep
      positive AAV as detected by RCA. In summary, this study describes a general
      method to titrate rAAV, independently of the transgene and its expression, and to
      measure the level of contamination with adenovirus and rep-positive AAV.
      Furthermore, we report a new production procedure using adenoviral plasmids
      instead of virions and resulting in rAAV stocks with undetectable adenovirus
      contamination.

PMID- 9551618
TI  - Combination therapy with interleukin-2 and wild-type p53 expressed by adenoviral
      vectors potentiates tumor regression in a murine model of breast cancer.
AB  - Although cytokine gene transfer for cancer treatment can stimulate immune
      recognition and tumor regression in animal models, there is still a need for
      improvements to these strategies. In this study, we examined the efficacy of a
      combination gene therapy using adenovirus (Ad) 5 vectors expressing human
      interleukin-2 and the wild-type (wt) human p53 gene under control of the human
      cytomegalovirus immediate early promoter (AdIL-2 and Adp53wt, respectively).
      Infected murine cell lines and primary mouse tumor cells secreted high levels of
      IL-2 and over expressed the p53 protein for at least 9 days. After infection of
      cells with Adp53wt, DNA synthesis was significantly inhibited and apoptosis was
      induced within 3-5 days. Both vectors were tested in a transgenic mouse mammary
      adenocarcinoma model for antitumor response. Following a single intratumoral
      injection of mice bearing PyMT induced tumors, the combination of Adp53wt (1 x
      10(9) pfu) plus a relatively low dose of AdIL-2 (1.5 x 10(8) pfu) caused
      regressions in 65% of the treated tumors without toxicity. Fifty percent of the
      treated mice remained tumor free and were immune to rechallenge with fresh tumor
      cells. In contrast, injection of either vector alone at this does resulted in
      only a delay in tumor growth. Only mice co-injected with Adp53wt and AdIL-2
      showed specific antitumor cytolytic T lymphocyte (CTL) activity, indicating that
      the immune response involved in tumor regression was promoted by the combination
      therapy. These results suggest that cancer treatment strategies involving
      combined delivery of immunomodulatory and antiproliferative genes may be highly
      effective.

PMID- 9551619
TI  - Intercellular communication mediates the bystander effect during herpes simplex
      thymidine kinase/ganciclovir-based gene therapy of human gastrointestinal tumor
      cells.
AB  - A bystander effect is described when nontransduced or genetically unmodified
      cells are killed during death of genetically modified tumor cells transduced with
      a suicide gene. The "bystander effect" greatly enhances the efficacy of the
      herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy
      approach for cancer. The mechanism of the bystander effect is controversial. In
      this study, we examined the role of intercellular gap junction communication
      (GJIC) for the bystander effect in human gastrointestinal tumor cells. Our
      results show that the extent of the bystander effect varied amongst the tumor
      cell lines; pancreatic cancer cells BXPC-3 exhibited excellent bystander effects
      in vitro and in vivo studies whereas other gastrointestinal tumor cell lines such
      as pancreatic cancer cells MIAPACA-2, and colon cancer cells HT-29 showed poor
      bystander effects. Bystander effects were only found in the presence of cell-to
      cell contact. The extent of the bystander effect was independent of the level of
      HSV-TK activity in the transduced tumor cells and was correlated with GJIC as
      demonstrated by an in vitro dye-transfer assay. Expression of the mRNA levels of
      gap junction protein connexin 43 was 8- to 26-fold or greater and connexin 26
      gene expression was 2- to 229-fold greater in BXPC-3 cells compared to HT-29,
      MIAPACA-2, and PANC3 cells. Our results suggest that intercellular communication
      is essential for the bystander effect. The correlation between GJIC and the
      extent of the bystander effect suggest a role for GJIC in mediating the bystander
      effect. Analysis of tumors for GJIC or expression of gap junction proteins may
      identify the subset of patients suitable for gene therapy with the HSV-TK/GCV
      approach.

PMID- 9551620
TI  - Cancer gene therapy by direct tumor injections of a nonviral T7 vector encoding a
      thymidine kinase gene.
AB  - Previously, we described a nonviral cytoplasmic gene therapy vector system based
      on the T7 autogene concept. This system has been shown to achieve rapid and high
      levels of gene expression in a variety of animal cells and tissues. To test the
      utility of the system in vivo tumor ablation, a T7 cancer gene therapy plasmid
      vector, pT7T7/T7TK, was constructed. This nonviral vector contains a T7 autogene,
      T7T7, and a human herpes simplex virus thymidine kinase (HSV-TK) gene driven by a
      second T7 promoter (T7TK). When co-transfected with T7 RNA polymerase (T7 RNAP)
      into cultured human osteosarcoma 143B cells, abut 10-20% of the cells were found
      to express HSV-TK, and more than 90% of the cells were killed in the presence of
      1 microM ganciclovir (GCV) within 4 days after DNA transfection. The increase in
      killing above the transfection frequency is due to a "bystander" effect among
      transfected and untransfected 143B cells. Direct injections of pT7T7/T7TK into
      143B tumors grown in nude mice resulted in TK gene expression in tumor cells
      located near the injection sites as revealed by the immunohistochemical staining.
      Repeated tumor injections of the pT7T7/T7TK vector and intraperitoneal (i.p.)
      injections of GCV resulted in inhibition of tumor growth and in tumor shrinkage
      in 6 out of 10 treated nude mice. Three of those six tumors fully regressed
      shortly after the end of the GCV injections. All of the full tumor regressions
      were found to be permanent and no apparent tumor relapses were observed for the
      rest of the lives of the treated nude mice after the initial tumor ablations.
      These results, combined with the nonviral and rapid cytoplasmic gene expression
      features, suggest that the T7 vector may be a good candidate for cancer gene
      therapy and other medical and biological applications.

PMID- 9551621
TI  - Retroviral vector targeting to melanoma cells by single-chain antibody
      incorporation in envelope.
AB  - Two strategies for targeting recombinant retroviruses to melanoma cells were
      compared. One was to extend the tropism of an ecotropic envelope to human
      melanoma cells, the other was to enhance the tropism of an amphotropic envelope
      for melanoma cells. Chimeric retroviral envelopes, incorporating a single-chain
      antibody (ScFv) directed against high-molecular-weight melanoma-associated
      antigen (HMWMAA) at the amino terminus are correctly processed and incorporated
      into virions. ScFv-ecotropic envelope chimeras allow specific, but low-titer,
      targeting of HMWMAA-positive cells, when co-expressed with ecotropic envelopes.
      ScFv-amphotropic envelope chimeras bind specifically to HMWMAA-positive cells and
      allow preferential infection at high titer.

PMID- 9551622
TI  - Antisense c-myc retroviral vector suppresses established human prostate cancer.
AB  - Prostate cancer eventually becomes androgen resistant, resumes growth, and kills
      the patient. Characterization of genetic events that lead to androgen refractory
      prostatic neoplasia has revealed the frequent overexpression of c-myc and
      uncontrolled prostate cancer proliferation. A novel strategy to combat advanced
      prostate cancer utilized a replication incompetent retrovirus that contained the
      mouse mammary tumor virus (MMTV) promoter within the retroviral vector to allow
      transcription of antisense c-myc gene within target prostate tumor cells. The
      transduction of cultured DU145 cells by XM6:MMTV-antisense c-myc RNA retrovirus
      did not affect cell proliferation in culture, yet a single direct injection of
      MMTV-antisense c-myc viral media into established DU145 tumors in nude mice
      produced a 94.5% reduction in tumor size compared to tumors treated with control
      virus MTMV sense fos and untreated tumor by 70 days. Two animals in the antisense
      c-myc-treated group had complete regression of their tumors. Histopathological
      examination of the tumors revealed that MMTV-antisense c-myc-transduced DU145
      tumors had increased tumor cell differentiation, decreased invasion, and a marked
      stromal response. The mechanism for the antitumor effect of MMTV-antisense c-myc
      retrovirus appears to be suppression of c-myc mRNA and protein, and decreased bcl
      2 protein. The in vivo transduction of prostate cancer cells with MMTV-antisense
      c-myc retroviruses reduced tumor growth by suppressing c-myc, resulting in the
      down-regulation of bcl-2 protein. Consequently, the MMTV-antisense c-myc
      retrovirus may be useful for gene therapy against advanced, hormone-refractory
      prostate cancer.

PMID- 9551623
TI  - Microscopical localization on adenylate cyclase: a historical review of
      methodologies.
AB  - The histochemistry technique for localizing adenylate cyclase has been developed
      over the past two decades. Early efforts were directed at overcoming the
      criticism of the lead capture technique, the inhibition of the enzyme by
      fixation, and problems associated with the substrate. The introduction of
      alternative metal ions, strontium and cerium, offered solutions to the criticism
      of the lead capture technique. The inhibition of the enzyme by the various
      fixation methods used has been rarely overcome satisfactorily and the use of non
      fixed material during incubation is one of the alternatives that has been
      suggested. The introduction of adenylate (beta-gamma-methylene) diphosphate as an
      alternative substrate offers a solution to the problems associated with
      commercially available adenylyl imidodiphosphate. Although no standard medium or
      method has been accepted by all researchers, the histochemical technique still
      has a place in the arsenal of the modern cell biologist. The technique localizes
      the active enzyme, as opposed to the protein, active and nonactive, by
      immunocytochemistry and the precursors of the protein by in situ hybridization
      methods.

PMID- 9551624
TI  - Cerium ions in the histochemical demonstration of second-messenger enzymes.
AB  - Second-messenger systems are involved in the regulation of numerous cellular
      processes. Adenylate cyclase (AC) and guanylate cyclase (GC) enzymes are in key
      positions in the regulation of these systems. The cerium method has been
      successfully applied to demonstrate amine- and neuropeptide-stimulated AC in rat
      nervous and adipose tissues and human sweat glands at the electron microscopic
      level. AC was also localized in cultured neurons. Nitric oxide compounds
      stimulated GC were demonstrated in rat hippocampal areas. Enzyme reactions were
      located in neurons pre- and postsynaptically in synapses; in addition, GC
      activity was seen intraneuronally and in glial cells. Adipocytes and eccrine
      glandular cells exhibited reaction products in their plasmalemmas. Optimal
      histochemical conditions are described, combined with control experiments. Some
      handicaps, related to the sensitivity of the enzymes to the fixatives,
      penetration problems of cerium salts, and especially the specificity of the
      method in phosphatase enzyme histochemistry in general are discussed.

PMID- 9551625
TI  - Cytochemical localization of adenylate cyclase in the limb buds of Bufo bufo.
AB  - The importance of cyclic nucleotides in the regulation of the processes of
      differentiation and embryonic development is known. The possible role that cyclic
      adenosine monophosphate (cAMP) plays during the development of the posterior limb
      of Bufo bufo is studied by the cytochemical localization of adenylate cyclase
      (AC), an enzyme that catalyzes the synthesis of the cyclic nucleotide. The method
      is based on the reaction between the enzyme AC and its specific substrate AMP-PNP
      (5'-adenylylimidodiphosphate) in the presence of lead. The lead precipitates that
      form as secondary reaction products are evidence of enzymatic activity. Reaction
      products are present only at the epithelial level in the limb bud; initially,
      such products are visible only at the base of the bud, particularly on the
      epithelial fascia located at the boundary with the body. During successive
      elongation and toe formation, AC activity is only present on the cells of the
      proximal portion of each new segment. Enzymatic activity is never present in
      correspondence to the ectodermal apical crest. cAMP is probably not involved in
      the processes of cellular proliferation but, rather, in the processes of inducing
      differentiation of the internal mesenchymal cells.

PMID- 9551626
TI  - Cytochemical localization of adenylate cyclase in cultured renal epithelial (A6)
      cells.
AB  - To characterize the vasopressin-adenylate cyclase (AC) signaling pathway in
      control of Na+ reabsorption in cultured renal (A6) cells, we determined the
      distribution of AC with a cytochemical technique using 5'
      adenylylimidodiphosphate as substrate and cerium chloride as capturing agent. The
      addition of forskolin to the medium to stimulate AC activity increased the
      production of reaction deposits at the enzyme sites. To ensure that the cells
      were close to their physiological states, cytochemical reactions were performed
      on unfixed tissues. Subsequent postfixation adequately preserved the
      morphological features of the cells. AC was mainly restricted to the lateral
      folds of the cells while the apical membranes were devoid of any deposits. This
      result provided evidence that the V2-AC pathway is not present in the apical
      membrane and, hence, any vasopressin action on apical Na+ channels from the
      luminal side of the cell must involve other signaling pathways. The cytochemical
      results provided further morphological evidence of the functional coupling
      between the basolateral and apical membranes of renal cells. We examined the idea
      that highly variable basal rates of Na+ transport in young differentiating cell
      cultures may be related to the degree of AC activity. Cytochemical results
      apparently revealed highly variable amounts of deposits in these cells, but by
      quantitative analysis of AC activity we could find no significant differences
      between cells of 6, 14, and 21 days.

PMID- 9551627
TI  - Cytochemical and biochemical studies on adenylate cyclase activity in
      preneoplastic and neoplastic liver tissue and cultured liver cells.
AB  - The ATP-analogue adenylyl(beta,gamma-methylene)diphosphonate was chosen as
      substrate for the cytochemical localization of adenylate cyclase (AC) activity.
      The tissues investigated covered normal rat liver and liver from carcinogen
      treated animals with preneoplastic lesions and hepatocellular neoplasms, as well
      as cultured liver cells. The AC reaction product methylene diphosphonate was
      precipitated with Pb2+ immediately at the place of production. This approach
      permitted a precise localization of AC activity by light and electron microscopy.
      The specificity of the AC reaction was demonstrated by control reactions,
      including inhibition of AC with 2'5'-dideoxyadenosine and activation with
      forskolin, glucagon, and cholera toxin. Endogenous phosphatases were inhibited
      with tetramisole and NAD. In normal liver, AC activity was mainly localized in
      the sinusoidal membrane of hepatocytes. A distinct gradient in activity was
      observed within the liver lobule. Hepatocytes localized around the terminal
      hepatic venule showed a significant higher AC activity compared to hepatocytes
      near the portal tract. AC was clearly decreased in focal preneoplastic liver
      lesions of the glycogenotic-basophilic cell lineage leading to hepatocellular
      carcinomas. Cytochemically detected intensity of AC activity corresponded to data
      obtained by microbiochemical assays in laser-dissected tissue samples. A
      remarkable interdependence of AC activity and degree of differentiation was also
      seen in epithelial rat liver cell lines: Highly differentiated cells show high
      enzyme activity and vice versa, as shown by both cytochemical and biochemical
      examinations. It is concluded that alterations in cellular signal transduction
      caused by alterations in AC activity play an important role in
      hepatocarcinogenesis.

PMID- 9551628
TI  - Adenylyl cyclase in the heart: an enzymocytochemical and immunocytochemical
      approach.
AB  - This review provides a discussion of the localization of adenylyl cyclase (AC) in
      normal mammalian heart tissue employing enzymocytochemistry (detection of the
      catalytic activity of AC by a metal precipitation technique) and
      immunocytochemistry (immunolabeling of the enzyme protein with antibodies against
      AC subtypes). By the metal precipitation technique, AC activity was localized in
      adult guinea pig cardiomyocytes along the sarcolemma and the T-tubule membranes.
      This reaction can be enhanced by hormones and guanylyl imidodiphosphate,
      fluoride, and forskolin. With this technique, no precipitates were detected at
      the sarcoplasmic reticulum. However, under ischemic conditions, AC activity was
      also found in the junctional sarcoplasmic reticulum of rat cardiomyocytes.
      Immunocytochemistry revealed AC in the plasma membrane of rat cardiomyocytes.
      Detection of AC in the perinuclear space of cardiomyocytes might reflect
      initiation of synthesis and processing of the enzyme protein. Colocalization of
      AC with cytoskeleton fibers of non-cardiomyocytes emerging in the cell culture of
      neonatal rat cardiocytes imply a direct cytoskeletal-AC interaction. Finally, it
      can be stated that the immunolabeling pattern of AC in cryosections of adult and
      new-born rat hearts reveals a good correspondence with the localization of AC
      activity in cardiomyocytes demonstrated by enzymocytochemistry.

PMID- 9551630
TI  - Immunocytochemical localization of adenylyl cyclase in human myometrium.
AB  - The enzyme adenylyl cyclase (AC) plays a pivotal role in smooth muscle
      relaxation. Biochemical evidence suggests that AC is predominantly located in the
      outer layers of the myometrium; however, neither immunocytochemical nor
      histochemical studies have been undertaken to demonstrate the specific cellular
      distribution of the enzyme in this tissue. As part of an ongoing study of the
      human myometrium, a polyclonal antibody against types V and VI AC was used to
      detect the presence of these isoforms in sections of formalin-fixed, wax-embedded
      myometrial tissue. A positive reaction was seen in the cytoplasm of the smooth
      muscle cells with the midmyometrial area having the greatest number of positive
      cells, when compared to the subserosal and subendometrial areas. It is
      hypothesized that AC isoform type VI is the predominant isoform present in the
      myometrium and that the percentage distribution of positive cells reflects the
      area of highest myometrial activity during parturition.

PMID- 9551629
TI  - Intracellular distribution of adenylate cyclase in human cardiocytes determined
      by electron microscopic cytochemistry.
AB  - Subcellular localization of adenylate cyclase (AC) in human cardiocytes was
      studied by electron microscopic cytochemistry using ventricular biopsies from
      various diseased hearts. In addition to the weak enzyme activity on the
      sarcolemma, the intense reaction products of AC were demonstrated within
      distinctive morphologic components of sarcoplasmic reticulum, nuclear envelope,
      and other internal membranes such as parallel lamellar structures and interlaced
      tubular structures in the perinuclear regions and stacked membranous structures
      beneath sarcolemma in cardiocytes. The distribution and intensity of cytochemical
      activity within different organelles was variable among biopsy cases. The
      reaction products of AC cytochemistry within the sarcoplasmic reticulum could be
      related to signal transduction targeting Ca2+ handling by the organella.
      Cytochemical activity within the nuclear envelope and perinuclear internal
      membranes possibly reflects AC participation in a signal function to regulate
      nuclear activity, such as gene expression. Cytochemical distribution of the
      enzyme in membranous structures beneath the sarcolemma is most likely related to
      hormone receptors and the linked activity of AC. The subcellular distribution of
      AC on various internal membrane structures in cardiocytes may reflect
      compartmentalization of the enzyme at individual intracellular sites to regulate
      a preferential specific signal function among multiple potential signal
      transductions by a cascade of AC, cyclic AMP, and cyclic AMP-dependent protein
      kinase. Alternatively, subcellular localization of the reaction products may
      reflect local enzyme synthesis or represent sites of enzyme transport, e.g., to
      terminal localization beneath the sarcolemma.

PMID- 9551631
TI  - Ultramicrotomy on fretting wear debris.
AB  - A TEM-sample preparation method for small amounts of fretting wear debris is
      presented. After embedding in a resin, the debris are ultramicrotomed to ultra
      thin sections. In this way, valuable observation of nanocrystalline fretting wear
      debris originating from TiN-coatings could be rapidly obtained.

PMID- 9551632
TI  - Instrumental factors in infrared microspectroscopy.
AB  - Instrumentation is the cornerstone of infrared microspectrometry (IMS) technology
      and the foundation for all applications. The fundamental factors in IMS systems
      are presented from the perspective of an instrument developer. While the current
      state of instrument development is presented, speculation of future development
      is also included. The goal of IMS instrumentation is to produce the highest
      signal-to-noise ratio (SNR) spectrum with the highest spectral resolution from
      the smallest sample area. Detector response, spectrometer efficiency, source
      brightness, wavelength range, microscope optics and sample definition are factors
      limiting IMS instrument performance. The current performance and future trends in
      IMS instrumentation are presented in this work.

PMID- 9551633
TI  - Chemical imaging of nucleic acids, proteins and lipids of a single living cell.
      Application of synchrotron infrared microspectrometry in cell biology.
AB  - Hybridoma B-cells have been used as models to evaluate the performance of
      synchrotron infrared microscopy to obtain chemical images of a single living
      cell. Chemical mapping of nucleic acids, proteins and lipids at a resolution of a
      few microns, close to the diffraction limit in the mid-infrared region are shown.

PMID- 9551634
TI  - FT-IR microspectroscopic detection of metabolically deuterated compounds in the
      rat cerebellum: a novel approach for the study of brain metabolism.
AB  - Deuteration provides a novel means for studying metabolism in biological
      organisms and avoids the use of radioisotopes. Ingestion of D2O enriched drinking
      water causes deuterium to be metabolically incorporated into molecules within
      tissues. The incorporation of deuterium into various chemical functional groups
      then can be monitored via infrared spectroscopy. The excellent spatial resolution
      that can be achieved with Fourier transform infrared (FT-IR) microspectrometers
      allows collection of infrared spectra from select microscopic regions of tissue
      specimens. Thus, combining deuteration together with FT-IR microspectroscopy
      enables analysis of metabolic activities by probing subregions within the
      microscopic field. In the present study, adult rats were given drinking water
      containing 30% or 40% D2O for 5 1/2 weeks. Frozen sections were prepared from the
      cerebellum, and infrared spectra were collected from the molecular layer, granule
      cell layer and white matter with FT-IR microspectrometers, using both
      conventional and synchrotron sources. The CD:CH and ND,OD:NH,OH ratios were
      highest in the molecular layer and lowest in the white matter. The high ratios in
      the molecular layer are consistent with the active synthesis and recycling at
      synapses, which are abundant structures in this layer. The low levels in the
      white matter are consistent with radioactive measures that found slow turnovers
      of proteins and lipids in myelin, which is the main constituent of white matter.
      In addition to describing the metabolic incorporation of deuterium, a graphic
      description of the distribution of chemical functional groups in the various
      layers of the cerebellum is presented. In summary, this study demonstrates that
      FT-IR microspectroscopy in conjunction with administration of D2O in drinking
      water can be used to reveal relative metabolic activities in various layers of
      the cerebellum. We predict that metabolic activities in other tissues and tissues
      in different states, e.g., disease states, can be analyzed in a similar manner.

PMID- 9551635
TI  - Infrared microspectroscopic imaging of the cerebellum of normal and cytarabine
      treated rats.
AB  - Conventionally, the diagnosis of neuropathology in a subject requires the
      identification of a behavioral modification, which provides direction for
      appropriate histological analyses. However, since the ultimate diagnosis of the
      pathology largely depends on the initial choice of histological tests, the
      opportunity exists for inaccurate or insensitive results. An innovative approach
      using Fourier transform infrared (FT-IR) spectroscopic imaging to diagnose
      neuropathology should prove useful. This novel method monitors and visualizes the
      underlying chemistry of the tissue, based on hundreds of vibrational absorption
      bands that are intrinsic to the sample. As such, it makes no prior assumptions as
      to the type or degree of pathology. Using this technique, we have
      spectroscopically imaged cerebellar tissue slices from rats [control subjects and
      subjects treated with the antineoplastic drug, cytarabine (Ara-C)], and have been
      able to correlate lipid and protein distributions within distinct cell types in
      the cerebellum. A further benefit of the technique is that it simultaneously
      records tens of thousands of independent spectra from different spatial locations
      within the sample. Thus, a variety of statistical and multivariate techniques can
      be exploited to characterize large sample areas and to provide robust
      classification of individual spectral signatures. In comparison to standard
      histological protocols, FT-IR spectroscopic imaging simultaneously analyzes cell
      layers and identifies subtle structural and biochemical changes within the
      sample. We suggest that FT-IR spectroscopic imaging should provide a highly
      reliable, complementary tool for standard histological tier testing.

PMID- 9551636
TI  - Infrared crystallographic investigation of T-state hemoglobin.
AB  - Polarized IR measurements on single crystals of human hemoglobin, grown under low
      salt conditions that stabilize the T quaternary structure, allow spectral
      features to be associated with individual sites within the molecule. Differences
      between the a- and c-polarized IR spectra in the sulfhydryl stretching region
      distinguish the contributions of individual Cys residues to the S-H band and lead
      to an evaluation of possible H-bonding partners for Cys beta-112. Successful
      modelling of both crystal and solution S-H spectra with component bands having
      identical frequencies and bandwidths, supports the use of the X-ray structure as
      a model for the low affinity T-state in solution. Polarization analysis of a
      crystal partially saturated with CO reveals comparable occupancy of the alpha-
      and beta-hemes. In the T-state crystal, the C-O bands are broader and lower in
      frequency than in the R-state solution, and 20% of the CO-ligated beta-subunits
      adopt an alternate conformation with a 1967 cm(-1) C-O frequency. The latter
      observation reflects an energetically significant disruption of the distal heme
      pocket upon CO binding to beta-hemes in the low affinity T-state.

PMID- 9551637
TI  - Near-IR and IR imaging in lipid metabolism and obesity.
AB  - Approximately one-third of Americans are classified as obese. There has long been
      an interest in drug therapies for obesity. Interest in obesity research and in
      drug interventions in obesity has greatly increased since the discovery of a
      protein named leptin, one of apparently many competing biological signals in
      energy metabolism. The complexity of the obesity problem demands new non-invasive
      and non-destructive methods for monitoring lipid metabolism and energy
      expenditure to study the competing biological signals and their effects. A new
      computer algorithm for spectrometric imaging of living subjects is used to remove
      artifacts arising from subject motion from spectra and images. The algorithm is
      sufficiently simple to be implemented easily in hardware for real-time video
      processing. Because the algorithm can be applied to images, thermogenesis and
      lipid metabolism in interscapular adipose tissue can be observed directly in
      unrestrained and unanesthetized subjects using an InSb focal plane array video
      camera. The accuracy and precision of temperature and spectral measurements are
      established using laboratory references and prototype drugs in test subjects.

PMID- 9551638
TI  - FT-Raman, FT-IR spectroscopy and PIXE analysis applied to gallstones specimens.
AB  - Fourier transform Raman (FT-Raman) spectroscopy and Fourier transform infrared
      spectroscopy (FT-IR) were used as the main analytical techniques for the
      determination of human gallstone structural composition. These techniques provide
      rapid, qualitative and quantitative information about stone structure. The
      gallstones were obtained from. 40 patients during both surgical operations and
      laparoscopy. The results of FT-Raman and FT-IR analysis allowed to distinguish of
      four main groups of gallstones according their cholesterol and bilirubinate salt
      content. Our studies were extended to trace element analysis by means of proton
      induced X-ray emission (PIXE). On 14 elements detected, six elements Ca, Mn, Fe,
      Cu, Zn and Br were chosen for quantitative analysis. The concentration levels of
      these elements varied depending the chemical structure of the gallstones. The
      relationship between Ca and Cu appears to be of particular significance. In this
      paper a correlation between stone structure and trace element concentrations is
      presented.

PMID- 9551639
TI  - Characterization of silicone breast implant biopsies by Fourier transform
      infrared mapping.
AB  - Fourier transform infrared (FT-IR) spectral mapping was used to study polymers in
      human tissue associated with silicone breast implants. Biomaterials such as
      polyesters, polyurethanes and silicone were identified by FT-IR spectroscopy, and
      their relative locations and distributions within tissue specimens were
      characterized by three-dimensional (3D) spectral maps.

PMID- 9551640
TI  - Drug distribution in human hair by infrared microscopy.
AB  - Localization of drug metabolites within human hair is important in determining
      the pharmacokinetics of drug incorporation in hair. This information is critical
      to validate drug testing data from hair. Microspectroscopic probing of small
      areas within longitudinally microtomed hair sections provides a profile of the
      deposition of drug along a growth line and thus indicates localization as a
      function of time. Probing across individual hairs may reveal the
      hydrophobic/hydrophilic characteristics of the substance. Hydrophobic drugs tend
      to bind to the central core or medulla of the hair while hydrophilic drugs tend
      to be spread throughout the cortex of the hair and appear, generally, in lower
      concentrations per dose. Profiles of distribution with high spatial resolutions
      of the regions of the hair are necessary for these determinations. This
      information is available to a certain extent in normal infrared microscopy and
      enhanced in synchrotron powered infrared microscopy.

PMID- 9551641
TI  - Infrared microscopic functional group mapping and spectral clustering analysis of
      hypercholesterolemic rabbit liver.
AB  - Fourier transform infrared microscopy has been applied to the characterization of
      hypercholesterolemic rabbit liver. A combination of the traditional "group
      frequency" approach to spectral interpretation and the technique of functional
      group mapping was applied to aid understanding of the spectral changes observed
      between normal and hypercholesterolemic liver. Using this approach, spectral
      differences could be attributed to the accumulation of cholesterol esters (most
      likely in the form of lipoprotein complexes) in the hypercholesterolemic liver. A
      novel approach, spectral clustering, was used to identify regions of
      hypercholesterolemic liver tissue which possessed similar spectral (and by
      inference similar biochemical/histological) properties. Using this approach, a
      complex data set consisting of 400 discrete spectra acquired from an area of
      tissue approximately 1 x 1 mm could be reduced to five types of spectra, and the
      distribution of each type of spectrum within the tissue analyzed.

PMID- 9551642
TI  - FT-IR microspectroscopic imaging of flax (Linum usitatissimum L.) stems.
AB  - Fourier transform infrared (FT-IR) microspectroscopy was used to image and
      subsequently produce maps of the distribution chemical components in flax stem
      tissue. Cross-sections of two flax cultivars, Ariane and Natasja, were examined.
      The infrared maps produced were keyed to the visible images of the samples, thus
      permitting superimposition of chemical composition onto anatomical structure. The
      functional group frequencies utilized to produce chemical maps were based on
      their diagnostic capability for indicating each component to the exclusion of
      others in the matrix, by comparison of the spectra of "pure" components. Waxes
      were best indicated by a sharp shoulder at 2850 cm(-1) and appeared primarily in
      the cuticular and epidermal tissues. Pectins gave a band ca. 1615 cm(-1) for the
      Ca2+ salt form that was primarily detected in tissue surrounding the fiber
      bundles. Cellulose was the strongest contributor to the band located at ca. 1335
      cm(-1) that showed its greatest intensity in the fiber cells. Aromatic compounds
      were indicated most readily by the band at 1510 cm(-1) and were located primarily
      in the core tissue. Acetyl groups, likely associated with hemicellulosic
      polysaccharides, were indicated by a band centered at 1250 cm(-1) and found
      within the fibers and core tissue.

PMID- 9551643
TI  - Infrared microspectroscopic imaging of biomineralized tissues using a mercury
      cadmium-telluride focal-plane array detector.
AB  - A 64 x 64 mercury-cadmium-telluride focal-plane array detector attached to a
      Fourier transform infrared microscope was used to spectroscopically image 5
      microm sections of canine alveolar bone tissue in the fingerprint region of the
      infrared spectrum. By ratioing the relative intensities of specific bands across
      the images, it is possible to obtain spatial distributions of the mineral-to
      matrix ratio and mineral maturity as a function of distance from an osteon.

PMID- 9551644
TI  - A method for examining the chemical basis for bone disease: synchrotron infrared
      microspectroscopy.
AB  - Infrared microspectroscopy combines microscopy and spectroscopy for the purpose
      of chemical microanalysis. Light microscopy provides a way to generate and record
      magnified images and visibly resolve microstructural detail. Infrared
      spectroscopy provides a means for analyzing the chemical makeup of materials.
      Combining light microscopy and infrared spectroscopy permits the correlation of
      microstructure with chemical composition. Inherently, the long wavelengths of
      infrared radiation limit the spatial resolution of the technique. However,
      synchrotron infrared radiation significantly improves both the spectral and
      spatial resolution of an infrared microspectrometer, such that data can be
      obtained with high signal-to-noise at the diffraction limit, which is 3-5 microm
      in the mid-infrared region. In this study, we use infrared microspectroscopy to
      study the chemical composition of bone using two mapping methods. In the osteon
      method, linear maps are collected from the center of an osteon (newer bone) to
      the periphery (older bone) and their chemical compositions are compared. In the
      transverse method, applied specifically to subchondral bone, line maps are
      collected from the edge of the articular cartilage (older bone) to the marrow
      space (newer bone). A significant advantage of infrared microspectroscopy over
      other chemical methods is that the bone does not need to be homogenized for
      testing; we are able to study cross-sectional samples of bone in situ at a
      resolution better than 5 microm and compare the results with morphological
      findings on stained serial sections immediately adjacent to those examined by
      infrared microspectroscopy. The infrared absorption bands of bone proteins and
      mineral are sensitive to mineral content (i.e. carbonate, phosphate, acid
      phosphate), mineral crystallinity and the content/nature of the organic matrix.
      In this study, they are analyzed as a function of (1) age, i.e. distance with
      respect to the center of an osteon, and (2) morphology, i.e. cortical versus
      cancellous (notably subchondral) bone. Results show that the protein/mineral
      ratio is higher in younger bone. As bone matures, mineralization increases, as
      does carbonate substitution into the hydroxyapatite lattice. Finally, most of the
      changes in chemical composition of bone occur within 20 microm of the site of new
      bone growth, e.g. the center of an osteon, demonstrating the need for the high
      spatial resolution achieved only with the use of a synchrotron infrared source.

PMID- 9551645
TI  - An approach to the study of primitive thrombocythemia (PT) megakaryocytes by
      means of Fourier transform infrared microspectroscopy (FT-IR-M).
AB  - Chronic myeloid leukemia (CML), polycythemia vera (PV), idiopathic myelofibrosis
      (IM) and primary thrombocythemia (PT) are myeloproliferative diseases of clonal
      origin. Megakaryocyte series are commonly involved in these disorders. In a
      previous paper of us, megakaryocytes (MKs) from PV and PT patients were shown to
      be more pathological with respect to the MKs from CML. This paper describes a
      Fourier transform infrared microspectroscopy (FT-IR-M) study analyzing the
      cytoplasm and nucleus areas of MKs from thrombocythemic patients which exhibited
      numerous giant cells (from 100 to 190 microm in diameter). The size of these
      cells makes it possible to analyze the cell parts using FT-IR-M technique. The
      infrared determinations on 10 single MKs for each case examined in these two
      different cell regions revealed spectral differences with a high degree of
      reproducibility. Finally, the spectra of whole MKs from normal donors and from
      thrombocythemic patients were also compared.

PMID- 9551646
TI  - Fourier transform infrared and Raman microspectroscopy of materials in tissue.
AB  - Fourier transform infrared and Raman (FT-IR and FT-Raman) microspectroscopy were
      used to study materials found in human tissue. Individual cases involving
      cholesterol, calcium stearate, and a polystyrenesulfonate ion exchange resin
      demonstrate the utility of the spectroscopic data. Characteristic spectral bands
      for these materials were compared with those of authentic chemical species to
      confirm their identities. The role of vibrational spectroscopy in pathologic
      diagnoses is discussed.

PMID- 9551647
TI  - Ultraspatially-resolved synchrotron infrared microspectroscopy of plant tissue in
      situ.
AB  - Routine use of 6 microm or 12 microm apertures with synchrotron microspectroscopy
      provide good spectra without excessive co-addition of scans. 100% mapping by
      stepping in pixel sized increments reveals chemical heterogeneity within cellular
      dimensions. The brightness of the synchrotron source and the absence of thermal
      noise compared to a conventional thermal (globar) source yields favorable signal
      to-noise operation. The nondivergent characteristics of the source result in
      minimal loss of radiation at the aperture, hence, spatial resolution approaches
      the diffraction limit. Details of cellular dimensions are then localized within
      any maps produced and individual spectra obtained from adjacent pixels clearly
      shows the striking difference in chemistry even within a microscopic vicinity. In
      this report the mapping of plant tissue with the synchrotron is contrasted to
      previous lower spatial resolution mapping experiments done with the globar on
      similar materials using interpolation between separated sampling spots and larger
      apertures.

PMID- 9551648
TI  - The analysis of exfoliated cervical cells by infrared microscopy.
AB  - The screening technique developed by Dr. Papanicolau for cervical cancer has
      significantly increased opportunities for early detection and treatment of this
      disease. Recently there has been a great deal of concern related to the accuracy
      of the Pap smear screening technique for cervical cancer and the need for highly
      skilled technologists to reliably examine the prepared samples. The use of
      infrared spectroscopy as a technique to discriminate between normal and malignant
      cervical cell samples has been reported by several research groups. Samples of
      cervical cells can be prepared for spectroscopic diagnosis by centrifuging cells
      obtained by the normal Pap smear technique and applying them to an infrared
      transparent window. A major concern with diagnosis by infrared spectroscopy is
      the homogeneity of the sample and whether the spectral features used in the
      analysis are caused by localized groups of cells or can be attributed to the
      majority of the cells in the sample. In this paper we report on the use of
      automated infrared microscopic mapping techniques to measure the infrared spectra
      at fixed intervals across the sample covering a 5 mm spot. Various post
      processing techniques have been applied to the spectral results to create images
      revealing specific features of the sample. The techniques applied to the data
      include: 1) Baseline corrected peak height; 2) Band ratioing to compensate for
      thickness; 3) Correlation metrics; 4) Similarity matching, and 5) Mahalanobis
      distance classification algorithm.

PMID- 9551649
TI  - Infrared microspectroscopy and artificial neural networks in the diagnosis of
      cervical cancer.
AB  - Infrared spectra of 88 normal and 32 abnormal (mild to severe dysplasia) cervical
      smear samples were used as a databank to investigate the usefulness of artificial
      neural networks (ANN) in the diagnosis of cervical smears. The spectra were first
      reduced, using principal component analysis (PCA), to seven wavenumber components
      that are the major contributors to the variance. A number of different ANN
      architectures were investigated that could differentiate between normal and
      abnormal cervical smears. Although the ANNs were trained to differentiate only
      normal from abnormal smears, the results using an independent test data set
      indicated that within the abnormal category mild dysplasia could be distinguished
      from severe dysplasia. The results using this restricted data set indicate that
      neural networks coupled to infrared microspectroscopy could provide an
      alternative automated means of screening for cervical cancer.

PMID- 9551650
TI  - FT-IR microspectroscopic imaging of human carcinoma thin sections based on
      pattern recognition techniques.
AB  - FT-IR microspectroscopic maps of unstained thin sections from human melanoma and
      colon carcinoma tissues were obtained on a conventional infrared microscope
      equipped with an automatic x, y stage. Mapped infrared data were analyzed by
      different image re-assembling techniques, namely functional group mapping
      ("chemical mapping") and, for the first time by cluster analysis, principal
      component analysis and artificial neural networks. The output values of the
      different classifiers were recombined with the original spatial information to
      construct IR-images whose color or gray tones were based on the spatial
      distribution of individual spectral patterns. While the functional group mapping
      technique could not reliably differentiate between the different tissue regions,
      the approach based on pattern recognition yielded images with a high contrast
      that confirmed standard histopathological techniques. The new technique turned
      out to be particularly helpful to improve discrimination between different types
      of tissue structures in general, and to increase image contrast between normal
      and cancerous regions of a given tissue sample.

PMID- 9551651
TI  - Biochemical imaging and 2D classification of keratin pearl structures in oral
      squamous cell carcinoma.
AB  - Precise regulation of cell organization results in well-differentiated tissue
      structures and continuous renewal of the oral epithelium maintaining a highly
      ordered tissue architecture. Here we demonstrate that FT-IR microspectroscopy,
      performed on sections of cancerous tissue biopsies, is capable of generating
      biochemical maps that show the distribution and any abnormal concentration of
      individual classes of biomolecules. Oral epithelia affected by cancer (squamous
      cell carcinoma) show many abnormal changes in morphology, of which the formation
      of keratin pearls is only one. Spectra from selected pearl areas demonstrate that
      these structures contain not only abnormal keratin concentrations but also seem
      to be stabilized by surrounding collagen fibers. Infrared image maps reveal that
      in the center of keratin pearls the concentration of protein (cytokeratins) is
      abnormally high, that DNA is absent and that the cell membrane fluidity is
      reduced. This suggests that cells are structurally destroyed and transformed into
      nuclei-free horny cells, simulating normal differentiation and epithelial growth.
      We also introduce a new analysis modality, two-dimensional (2D) tissue
      classification, and apply it to establish spectral similarities between different
      tissue structures. A total of 315 spectra, recorded for the original map, were
      analyzed by pattern recognition methods, classified and re-assembled into new
      maps based on their spectral similarities. The re-assembled maps clearly indicate
      significant tissue changes outside the pearls, suggesting early biochemical
      changes that accompany abnormal growth. Employing this 2D analysis modality in
      combination with infrared histopathology may be relevant to tumor diagnosis and
      prognosis.

PMID- 9551652
TI  - A new, non-destructive method for analysis of clinical samples with FT-IR
      microspectroscopy. Breast cancer tissue as an example.
AB  - A new method for infrared analysis of tissues and cells is presented. The method
      is based on Fourier transform infrared microspectroscopy coupled with attenuated
      total reflectance. The technique allows spectroscopic measurements on the same
      samples used by pathologists for histopathological evaluation, e.g. stained
      samples on plain glass slides. Since the same specimen can be used as for
      histopathology, the method does not require sample preparation or modification.
      Significantly, the sample is not damaged. Glass absorbs in the infrared and thus
      has not been used previously in infrared analysis of tissues and cells.
      Conventional infrared techniques utilize expensive substrates, such as BaF2
      windows and gold coated slides which do not absorb infrared radiation. However,
      these measurements require special preparation and result in the destruction of
      the sample. Breast cancer tissues were examined to demonstrate the feasibility
      and reproducibility of the new method. Linear discriminant analysis was used to
      discriminate and classify three types of cells: benign, atypical hyperplasia and
      malignant. It was demonstrated that benign vs. malignant cells were discriminated
      with 100% accuracy, benign vs. atypical hyperplasia were discriminated with 100%
      accuracy and malignant vs. atypical hyperplasia were discriminated with an
      accuracy of 90% and higher.

PMID- 9551653
TI  - Infrared spectroscopy of human tissue. IV. Detection of dysplastic and neoplastic
      changes of human cervical tissue via infrared microscopy.
AB  - Infrared absorption spectra of formalin-fixed, paraffin-embedded human cervical
      tissue are reported for normal, dysplastic and neoplastic samples. The spectral
      differences found in this study between these states of the tissues are far less
      than those observed for single cells by us and others. Nevertheless, we find a
      direct correspondence between spectral data from tissue sections, obtained from
      biopsies, and individual exfoliated cells, typically obtained during a pap
      procedure. We also find that spectra due to dysplastic samples fall about halfway
      between the spectral features of normal and cancerous samples.

PMID- 9551654
TI  - The in situ infrared microspectroscopy of bacterial colonies on agar plates.
AB  - The specular reflectance infrared spectra of thirty species of bacteria were
      obtained in situ, without their removal from the agar growth media, using the
      infrared microscope. Compared to transmittance spectra obtained from dehydrated
      films, the transformed reflectance spectra show significant band shifts which are
      greater for gram positive bacteria. The most notable shift occurs in the v[a](PO2
      ) band which shifts 8 cm(-1) higher upon removal of water. In addition, some
      measure of the differentiation potential of our in situ reflectance spectra was
      gathered by using principal components regression as a method of discrimination.
      We assigned a +1 for a gram positive property and a -1 to a gram negative
      property for each different bacteria species. The prediction results from a cross
      validation show that all the gram positive bacteria retain positive values for
      Gram stain predictions while all the gram negative species retain their negative
      values, suggesting a simple marker for differentiation. Overall, using
      reflectance spectra from colonies directly on the agar requires no sample
      preparation and provides slightly better differentiating spectral information
      than the transmittance spectra of dehydrated films.

PMID- 9551655
TI  - Raman spectroscopic analysis of Tet repressor-operator DNA interaction in
      deuterium oxide.
AB  - Tet repressor (TetR) plays a central role in the regulation of its own gene and
      in that of TetA, a resistance protein against the antibiotic tetracycline (Tc).
      In the absence of Tc, the TetR dimer binds with two alpha-helix-turn-alpha-helix
      motifs to two successive major grooves of operator DNA. In order to elucidate
      structural features of the TetR:operator complex, we measured the Raman spectra
      of the TetR protein, a 18-mer oligonucleotide with sequence corresponding to TetR
      operator DNA, and the TetR:operator complex in D2O. The spectra confirm and
      extend previously obtained results in H2O: i) B-DNA conformation is conserved
      with only small perturbations of the backbone geometry; ii) TetR and operator DNA
      interact at major groove sites, as evident from intensity changes of thymine and
      guanine bands; iii) Minor changes of TetR secondary structure are indicated upon
      operator binding, and iv) Local environments of aromatic amino acids are altered
      in the complex. These spectroscopic findings are consistent with a molecular
      model proposed of the basis of genetic and biochemical studies.

PMID- 9551656
TI  - Comparison of fresh and post-mortem human arterial tissue: an analysis using FT
      IR microspectroscopy and chemometrics.
AB  - Fourier transform infrared (FT-IR) microspectroscopy and chemometric methods have
      been applied to the study of fresh and simulated post-mortem human arterial
      tissue. The results have shown that although physical differences were observed
      using light microscopy, no spectroscopic distinction could be made between these
      groups. The presence of collagen throughout the artery wall results in
      characteristic absorptions which may mask any biochemical changes that could
      otherwise have been detected by the FT-IR technique. Because the structure of the
      artery is unique, these findings should be regarded as tissue specific.

PMID- 9551657
TI  - FT-IR spectroscopy as an emerging method for rapid characterization of
      microorganisms.
AB  - Statistical methods such as principal component analysis and cluster analysis
      were used to analyze ATR-FT-IR spectra obtained from bacterial whole cells. Both
      methods gave satisfactory results and are conclusive in showing that they can
      discriminate and classify bacterial strains of clinical origin exhibiting
      different resistance mechanisms. This approach places FT-IR spectroscopy at the
      forefront of those new potential techniques that could be used in the rapid
      screening of microorganisms.

PMID- 9551658
TI  - Posttranslational changes in band 3 in aging and Alzheimer's disease: do anion
      and glucose transport changes reflect or foreshadow the eventual metabolic
      abnormalities?

PMID- 9551659
TI  - Role of epidermal growth factor and insulin-like growth factor-I on porcine
      oocyte maturation and embryonic development in vitro.
AB  - The effects of epidermal growth factor (EGF) and insulin-like growth factor-I
      (IGF-I) on the in vitro maturation of porcine oocytes were examined. Oocytes
      obtained from the ovaries of slaughtered prepubertal gilts were matured in
      modified Medium 199 supplemented with 25% porcine follicular fluid and
      gonadotropins, and fertilized in vitro. Oocytes were either fixed 16 h later to
      assess fertilization or cultured for 7 days to assess embryonic development. In
      Experiment 1, the addition of EGF to maturation medium increased the percentage
      of meiotically mature oocytes (88% v. 70%; P < 0.001) but did not affect the
      proportion of fertilized or cleaved oocytes. Blastocysts derived from oocytes
      matured in medium supplemented with 10 ng mL(-1) EGF had a greater number of
      cells compared with those of control blastocysts (51.1+/-5.1 v. 36.0+/-3.1; P <
      0.02). In Experiment 2, the addition of IGF-I to maturation medium had no effect
      on meiotic maturation, fertilization or embryonic development. Our findings
      demonstrate that EGF plays an important role in both the meiotic and cytoplasmic
      maturation of porcine oocytes in vitro.

PMID- 9551660
TI  - Triosephosphate metabolism by mature boar spermatozoa.
AB  - Boar sperm rapidly interconverted dihydroxyacetone phosphate and glyceraldehyde 3
      phosphate, produced fructose-1,6-bisphosphate, approximately equilibrium
      concentrations of fructose 6-phosphate and glucose 6-phosphate but not glycerol
      or glycerol 3-phosphate. In the presence of 3-chloro-1-hydroxypropanone, an
      inhibitor of stage 2 of the glycolytic pathway, the triosephosphates were
      metabolized faster, produced less fructose-1,6-bisphosphate, fructose 6-phosphate
      and glucose 6-phosphate, but not glycerol or glycerol 3-phosphate. This suggests
      that these cells may have the capacity to convert glycolytic intermediates into a
      storage metabolite to conserve carbon atoms for the eventual synthesis of
      lactate.

PMID- 9551661
TI  - Metabolic activity of hypotonically treated mature boar spermatozoa.
AB  - Treatment of washed boar sperm with hypotonic phosphate buffer removed the
      acrosome, disrupted the cytoplasmic membrane and almost completely separated the
      heads from the mid piece-tail segment. As assessed by oxygen uptake studies and
      their ability to oxidize 14C-labelled substrates to 14CO2, hypotonically-treated
      cells exhibit low glycolytic activity yet mitochondrial activity remains high.
      Both lactate and glycerol 3-phosphate underwent oxidation and these substrates
      continued to be metabolized by this preparation which had been stored for up to
      10 days at 4 degrees C. Such preparations may be of assistance in the
      investigation of the biochemistry of boar sperm mitochondria.

PMID- 9551662
TI  - Seasonal patterns of luteal cyclicity in young red deer (Cervus elaphus) and
      sambar deer (Cervus unicolor).
AB  - Seasonal onset of pubertal ovulation and incidence of luteal cyclicity was
      assessed from plasma progesterone profiles over 15 months for tame red deer (n =
      7) and sambar deer (n = 7) hinds. Seasonal responses to photoperiod were
      determined from plasma prolactin profiles. All red deer attained puberty at 17-18
      months of age in May-June and expressed 3-6 luteal cycles of length 20.0+/-10.4
      days (mean+/-s.e.m.) over 52-102 days. Six sambar deer attained puberty at 7-19
      months of age, between August and December. Duration of luteal cyclicity was
      variable. While one animal remained continuously cyclic for 13 months, most
      entered anoestrus between November and February. The mean length of the luteal
      cycle was 17.2+/-0.3 days. While red deer exhibited strongly seasonal patterns of
      prolactin secretion, sambar deer showed no such seasonal trends. The data
      collectively indicate that young sambar hinds at temperate latitudes exhibit
      loosely defined patterns of reproductive seasonality that are 4-6 months out of
      phase with those of red deer, although some individuals may be non-seasonal.
      Failure to express seasonal patterns of prolactin secretion indicates that sambar
      deer may not perceive photoperiodic cues to the same extent as do red deer.

PMID- 9551663
TI  - A competitive enzyme immunoassay for follicle-stimulating hormone in ovine plasma
      using biotin-streptavidin amplification.
AB  - To determine follicle-stimulating hormone (FSH) concentration in ovine plasma, a
      second-antibody enzyme immunoassay using biotin-streptavidin amplification (BS
      EIA) was developed and was validated by comparison with a routine
      radioimmunoassay (RIA). Ovine FSH was labelled with D-biotinyl-epsilon
      aminocaproic acid-N-hydroxysuccinimide ester (biotin-7-NHS). The minimum and
      maximum detection limits were 0.40 ng mL(-1) and 25.0 ng mL(-1) respectively in
      the BS-EIA. Plasma samples from three superovulated ewes were measured for FSH by
      both BS-EIA and RIA. Correlation between values obtained by BS-EIA and RIA was
      0.86 (n = 106), and the linear regression had a slope of 0.88 and an intercept of
      -0.07 (R2 = 0.74). The baseline of BS-EIA was slightly lower than that of RIA
      (0.69 ng mL(-1) v. 1.10 ng mL(-1)). The intra-assay and inter-assay coefficients
      of variation in BS-EIA were 13.8% and 16.7% (n = 106) respectively. The recovery
      rates were 104.8+/-2.7% (mean+/-s.e.m., n = 14). Changes in plasma FSH
      concentration from superovulated ewes evaluated by BS-EIA corresponded well with
      the results of routine RIA.

PMID- 9551664
TI  - Effect of enucleation on protein synthesis during maturation of bovine oocytes in
      vitro.
AB  - The role of the nucleus in protein synthesis reprogramming during oocyte
      maturation was examined in immature or mature bovine oocytes, enucleated at the
      germinal vesicle (GV) stage or the metaphase II (MII) stage. Cumulus-oocyte
      complexes (COCs) were denuded before or after maturation in vitro. Denuded
      oocytes were (i) enucleated at the GV or MII stage (after DNA staining and
      ultraviolet (UV) exposure), (ii) stained and exposed to UV but not enucleated, or
      (iii) used as controls. After treatment, oocytes were labelled for 4 h with 35S
      methionine or were matured for 24 h before labelling. GV- or MII- karyoplasts and
      small portions of cytoplasm (cytoplasts), removed during enucleation, were also
      labelled. Labelled oocytes, karyoplasts or cytoplasts were prepared for one
      dimensional polyacrylamide gel electrophoresis. Incorporation of labelled
      methionine into oocyte protein was measured. Enucleation did not affect protein
      synthesis reprogramming, but incorporation of 35S-methionine in immature UV
      stained oocytes was high--possibly due to nuclear repair mechanisms. Protein
      profiles of GV- and MII- karyoplasts differed from those of immature and mature
      oocytes. In conclusion, normal protein synthesis reprogramming in the cytoplasm
      can occur in the absence of the nucleus, and specific proteins are synthesized in
      the nuclear region.

PMID- 9551665
TI  - Effect of iron on transferrin receptor expression by human placental
      syncytiotrophoblast cells.
AB  - Transferrin receptor expression has been examined in primary cultures of
      morphologically differentiated placental syncytiotrophoblast cells. More than 90%
      of the cells were multinucleated. Incubation of syncytiotrophoblast for 4 days in
      the presence of iron salts had no effect on receptor expression assessed by
      measuring the binding of 125I-labelled transferrin. However, incubation of cells
      in the presence of human diferric transferrin (10-100 microM) led to a 50%
      decrease in surface and intracellular receptor expression. This down-regulation
      was not accompanied by a significant decrease in receptor synthesis. In contrast
      to syncytiotrophoblast, expression of intracellular transferrin receptors in non
      differentiated cytotrophoblast cells decreased when cells were cultured with iron
      salts; this was accompanied by decreased receptor synthesis. Addition of diferric
      transferrin to cytotrophoblast cells led to a 50% reduction in surface and
      intracellular receptor expression, similar to that seen in the
      syncytiotrophoblast. This reduction was accompanied by a decrease in receptor
      synthesis. In contrast to that of most cell types, the expression and
      distribution of trophoblast transferrin receptors were not altered by insulin,
      epidermal growth factor or hydrocortisone. These characteristics of
      syncytiotrophoblast transferrin receptor expression may assist in ensuring a
      supply of iron to the fetus regardless of the maternal iron status.

PMID- 9551666
TI  - Homeobox gene HB24, a regulator of haematopoiesis, is a candidate for regulating
      differentiation of the extra-embryonic trophoblast cell lineage.
AB  - Expression of the human homeobox gene HB24 in the cytotrophoblast stem cell
      population in first-trimester human placenta was investigated. HB24 expression
      was downregulated after cytotrophoblast had differentiated into
      syncytiotrophoblast. Expression of HB24 was also detected in first-trimester
      invasive extravillous cytotrophoblast cells. In term placenta, HB24 expression
      was detected in residual cytotrophoblast cells and in syncytiotrophoblast.
      Northern analysis revealed two HB24 transcripts in first-trimester placenta of
      approximately 2.5 kb and 5.3 kb. Ribonuclease protection assays were used to
      confirm expression of HB24 in first-trimester and term placenta and also to
      provide evidence that HB24 is downregulated in choriocarcinoma cell lines. In
      addition to being required for differentiation of the haematopoietic cell
      lineage, HB24 may be required for differentiation of the extra-embryonic
      trophoblast cell lineage.

PMID- 9551667
TI  - Effect of hormone pre-treatment of prepubertal sheep on the production and
      developmental capacity of oocytes in vitro and in vivo.
AB  - Twenty 3-6-week-old Merino lambs were given either 3, 1 or 0 treatments of 50
      microg oestradiol benzoate and (48 h later) a 1.5 mg Norgestamet implant left in
      situ for 9 days (3-, 1- and 0CYCLE+G). On Day 7 after the last implant insertion,
      and on the same day for 0CYCLE+G, each lamb received 400 I.U. pregnant mare serum
      gonadotrophin and 6 mg follicle-stimulating hormone (FSH). The reproductive
      tracts were removed for oocyte collection 24 h after FSH. Reproductive tracts
      were also collected from 16-24-week-old lambs (n = 31) (0CYCLE-G). The number of
      antral follicles per ovary was similar for the 3-, 1- and 0CYCLE+G treatments.
      Similar rates of in vitro maturation and monospermic fertilization were obtained
      for all groups. The proportion of blastocysts per cleaved oocyte was higher for
      1CYCLE+G (50.5%) than for 3CYCLE+G (32.9%), 0CYCLE+G (24.3%), and 0CYCLE-G
      (11.8%) (P < 0.05). Viable fetuses were obtained at Day 93 of pregnancy after
      transfer of embryos from all treatments. These results indicate that a single
      treatment with oestrogen and progesterone, prior to gonadotrophin stimulation,
      will increase the yield and developmental capacity of oocytes from prepubertal
      sheep.

PMID- 9551668
TI  - Possible involvement of placental proteases in bradykinin (BK) degradation.
AB  - The hydrolysis of bradykinin (BK) by human placental subcellular fractions and
      pregnancy sera was studied in the presence of inhibitors by measuring amino acids
      liberated from BK by high-performance liquid chromatography. The effects of the
      inhibitors DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (MGTA, for
      kininase I), phosphoramidon (for endopeptidase 24.11) and captopril and
      rentiapril (for angiotensin-converting enzyme [ACE, kininase II]) suggested the
      essential roles of the above three proteases in BK degradation: among the three
      proteases, kininase I and endopeptidase 24.11 appeared to be the most important
      in kininase action in the placenta microsomes, whereas kininase I and ACE
      appeared to be the most important in kininase action in the placental cytosol,
      lysosome and pregnancy serum. Measurements of BK concentrations in the umbilical
      arterial blood, umbilical venous blood and maternal plasma revealed higher
      concentrations in the mother than in the fetus. The present data suggest that
      degradation of BK in the placenta and pregnancy serum might contribute to the
      gradient of BK between mother and fetus.

PMID- 9551669
TI  - Preliminary characterization of a placental factor inhibiting breathing in fetal
      sheep.
AB  - Previous studies have revealed a placental extract that inhibits breathing in
      fetal sheep. In the present study of 29 chronically instrumented sheep at 132+/-1
      days of gestation, infusion of the 1-10 kDa extract inhibited breathing in 76% of
      the experiments whereas Krebs' solution inhibited it in 24%. It retained this
      activity after 6 months of freezing, after lyophilization, and upon lowering the
      pH during purification from 8.0 to 4.0, but it inhibited breathing in only 35%
      when the pH was lowered to 2.0. A significant dose-dependent effect was observed
      from a 16-fold dilution to a 4-fold concentration. Treatment of the extract with
      proteinase K or boiling reduced the activity to 30% or 26% inhibition,
      respectively. The activity was not adsorbed to an ion-exchange column at pH 7.0
      or 8.0, but it was at pH 9.0 and it eluted with increasing NaCl concentrations.
      On a polyacrylamide gel the activity was eluted at a K(av) of 0.66 (82%
      inhibition), corresponding to between 2.5 and 4.5 kDa. These findings suggest
      that a peptide produced by the placenta, with a molecular mass between 2.5 and
      4.5 kDa, inhibits fetal breathing.

PMID- 9551670
TI  - Prostaglandin and progesterone production by bovine luteal cells incubated in the
      presence or absence of the accessory cells of the corpus luteum and treated with
      interleukin-1beta, indomethacin and luteinizing hormone.
AB  - This experiment examined production of prostaglandin (PG) F2alpha, PGE2 and
      progesterone by bovine luteal cells incubated with or without the accessory cells
      and treated with recombinant bovine interleukin-1beta (10 ng), indomethacin (5
      microg) or luteinizing hormone (50 ng). During pretreatment, progesterone
      production was similar in the luteal and luteal plus accessory cells, being
      greater in either of these than in accessory cells; PGF2alpha was greatest in
      luteal plus accessory, intermediate in accessory and lowest in the luteal cells;
      PGE2 was similar among all cell arrangements. Luteinizing hormone or luteinizing
      hormone plus indomethacin stimulated progesterone in the luteal and luteal plus
      accessory cells, this being similar in these two cell arrangements. Interleukin
      1beta stimulated PGF2alpha in luteal and luteal plus accessory cells, and tended
      to elevate PGF2alpha in accessory cells. Interleukin-1beta stimulated PGE2 in all
      cell arrangements. Indomethacin inhibited the interleukin-1beta-stimulated
      PGF2alpha and PGE2 release. Indomethacin or indomethacin plus luteinizing hormone
      inhibited basal PGE2 in luteal and luteal plus accessory cells. These data
      suggest that progesterone production is not influenced by the presence of
      accessory cells of the corpus luteum, that accessory and luteal cells produce
      appreciable amounts of PG, and that recombinant bovine interleukin-1beta
      stimulates PGE2 and PGF2alpha in the luteal and accessory cells.

PMID- 9551671
TI  - Use of famciclovir to prevent HBV reactivation in HBsAg-positive recipients after
      allogeneic bone marrow transplantation.
AB  - BACKGROUND/AIMS: Reactivation of chronic hepatitis B viral infection causes
      significant morbidity and mortality after bone marrow transplantation. Recently,
      nucleoside analogues, such as famciclovir, were found to have a direct
      suppressive effect on hepatitis B virus replication in both in vitro and in vivo
      studies. We have studied the effect of famciclovir on the incidence of hepatitis
      B virus reactivation and hepatitis after allogeneic bone marrow transplantation.
      METHODS: Eight hepatitis B surface antigen (HBsAg)-positive patients who received
      allogeneic bone marrow transplantation were given oral famciclovir 250 mg three
      times daily, starting at least 1 week prior to bone marrow transplantation and
      continuing for 24 weeks after transplantation. Clinical and serological outcomes
      in these patients were compared with 24 HBsAg-positive recipients of allogeneic
      bone marrow transplantation who did not receive famciclovir (historical
      controls). RESULTS: After bone marrow transplantation, there were five patients
      with hepatitis B virus reactivation among those who received famciclovir 250 mg
      three times daily. Four of these patients responded to increased dosages of 500
      mg three times daily and did not develop hepatitis. The remaining patient
      suffered from hepatitis related to hepatitis B virus reactivation. Compared to
      historical controls, there were fewer cases of hepatitis due to hepatitis B virus
      reactivation and veno-occlusive disease. The median follow-up was 701.6 days
      (range: 50-2346 days) with ten deaths (three due to hepatic failure related to
      HBV reactivation) in those who did not receive famciclovir and one death (due to
      hepatic failure related to graft-versus-host disease) in those who received
      famciclovir. CONCLUSIONS: Use of famciclovir significantly reduced hepatitis due
      to hepatitis B virus reactivation in HBsAg-positive recipients after allogeneic
      bone marrow transplantation.

PMID- 9551672
TI  - A pilot randomized, controlled trial of the effect of iron depletion on long-term
      response to alpha-interferon in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Some studies have suggested that hepatic iron may influence the
      response to interferon therapy in chronic hepatitis C patients. We conducted this
      randomized, controlled trial to evaluate the effect of iron depletion on: (1)
      aminotransferase activity and hepatitis C RNA levels; and (2) response to
      interferon therapy in 38 patients with elevated alanine aminotransferase levels
      and who were HCV RNA positive. METHODS: Seventeen patients underwent a 500-ml
      phlebotomy every 2 weeks until iron deficiency was achieved. Patients were then
      started on a 6-month course of alpha-interferon 2b (3 mu tiw). Controls were 21
      patients who were monitored for a 6- to 8-week period without phlebotomy prior to
      interferon therapy. Response to interferon was defined as loss of serum HCV RNA
      by reverse transcriptase-polymerase chain reaction. Serum HCV RNA was quantitated
      by bDNA technique. RESULTS: Alanine aminotransferase levels decreased in 15/17
      patients after phlebotomy. Mean alanine aminotransferase fell from 156.8 to 89.7
      U/l (p=0.008). Changes in iron indices and alanine aminotransferase after
      phlebotomy were not accompanied by changes in HCV RNA levels. In control
      patients, neither alanine aminotransferase nor HCV RNA levels changed during the
      observation period. At the end of 24 weeks of interferon therapy, 7/17
      phlebotomized patients had a response, compared to 6/21 control patients (p=ns).
      After 6 months of follow-up, 5/17 phlebotomized patients remained HCV RNA
      negative, in contrast to only 1/21 controls (p=0.07). CONCLUSIONS: Iron depletion
      led to a reduction in aminotransferase levels; this was not accompanied by
      changes in levels of hepatitis C RNA. There may be an improvement in the
      sustained response to interferon therapy, but this requires confirmation.

PMID- 9551674
TI  - Use of granulocyte macrophage colony stimulating factor alone or in combination
      with interferon-alpha-2b for treatment of chronic hepatitis C.
AB  - BACKGROUND/AIMS: We have evaluated the effect of granulocyte macrophage colony
      stimulating factor (GM-CSF) when utilized either alone or in combination with
      interferon for treatment of chronic hepatitis C virus (HCV). METHODS: A total of
      71 patients with chronic HCV, elevated alanine aminotransferase and normal
      hepatic function were enrolled into these studies. Nineteen patients who had
      previously failed to achieve both biochemical and virologic response during
      interferon therapy were treated with increasing doses of GM-CSF alone (65-250
      microg/m2 three times weekly) for 6 months. Another 52 patients who had not been
      previously treated with interferon entered a randomized controlled trial; 25 were
      treated with interferon alone (3 mU three times weekly) and 27 with a combination
      of interferon+GM-CSF (3 mU+250 microg/m2 three times weekly). All patients were
      treated for 6 months. Both groups were well matched for age, sex, race, serum
      alanine aminotransferase, HCV-RNA titer, liver histology score and cirrhosis.
      RESULTS: None of the patients treated with GM-CSF alone developed either
      biochemical or virologic response at any of the treatment dosages and mean HCV
      RNA titer remained unchanged from baseline during this therapy. For patients in
      the randomized controlled trial, biochemical and virologic responses were
      observed in 54% of interferon-treated patients compared to 31.8% for those
      treated with interferon+GM-CSF. Long-term sustained virologic response was
      observed in only one patient in each group. No significant differences were
      observed in HCV-RNA titer during the course of treatment. GM-CSF treatment was
      associated with a significant increase in total white blood cell count and
      absolute eosinophil count, which peaked within the first month of therapy and
      declined spontaneously during the remaining 5 months. CONCLUSION: GM-CSF either
      alone or in combination with interferon does not appear to be effective for
      treatment of chronic HCV.

PMID- 9551673
TI  - Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and
      2b therapy in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Alpha interferon induces aminotransferase normalization in about
      50% of patients with chronic viral hepatitis C. However, some patients who
      initially respond experience a relapse during the treatment period (breakthrough
      phenomenon). The aim of this study was to evaluate the prevalence of breakthrough
      and its relationship with the emergence of neutralizing anti-interferon
      antibodies. METHODS: We studied 172 patients with histologically proven chronic
      hepatitis C, treated with interferon alpha 2a or 2b 3 mega units three times a
      week for 6 months. For each patient, HCV RNA level (polymerase chain reaction and
      bDNA) and anti-interferon antibodies dosage were determined during therapy.
      RESULTS: Among 84 patients with initial response, 13 (15.5%) experienced
      breakthrough. The kinetics of alanine aminotransferase and HCV RNA levels were
      strongly correlated, suggesting that breakthrough is not due to a random alanine
      aminotransferase fluctuation during treatment, but to the reappearance of viral
      replication. Neutralizing anti-interferon antibodies emergence was observed in
      38.5% in patients with breakthrough, as compared to 9.0% and 2.8% of non
      responder and complete-responder patients, respectively (p<0.0005). By
      multivariate analysis, the only factor predictive of breakthrough was the
      emergence of neutralizing anti-interferon antibodies 3 months after the onset of
      therapy. CONCLUSION: Our results suggest that the emergence of neutralizing anti
      interferon antibodies during treatment may explain breakthrough in about one
      third of cases. Other causes may also be responsible for this phenomenon and they
      remain to be determined.

PMID- 9551675
TI  - Alpha-glutathione transferases in HCV-related chronic hepatitis: a new predictive
      index of response to interferon therapy?
AB  - BACKGROUND/AIM: The aim of this study was to evaluate if plasma levels of alpha
      glutathione-S-transferases (determined in basal conditions and monthly for 1 year
      during and 1 year after interferon therapy) could characterize patients who show
      only a primary response. METHODS: We studied 48 patients with biopsy-proven,
      hepatitis C virus ribonucleic acid positive chronic hepatitis treated with
      interferon: 18 were "Sustained Responders", 12 "Relapsers" and 18 "Non
      Responders". RESULTS: Relapsers showed higher basal levels of alpha-glutathione-S
      transferases, which remained higher than normal even when alanine
      aminotransferases normalized. No correlation was documented between alpha
      glutathione-S-transferase levels and all other parameters examined (alanine
      aminotransferases, gamma-glutamyl-transpeptidase, viremia, and histological
      activity index). CONCLUSIONS: These findings suggest that alpha-glutathione-S
      transferase levels may be considered a predictive index of response to interferon
      therapy in chronic hepatitis C patients.

PMID- 9551676
TI  - Detection of squirrel monkey retroviral sequences in interferon samples.
AB  - BACKGROUND/AIMS: Interferons have been used therapeutically in viral infections,
      and as immunomodulants in the treatment of different types of cancers.
      Interferons have been prepared from human lymphoid cell-lines, such as Namalwa,
      that contain integrated copies of squirrel monkey retrovirus proviral DNA.
      Squirrel monkey retrovirus is related to simian type D retroviruses, such as
      Mason-Pfizer monkey virus. Thus it is important to determine if these retroviral
      sequences are present in interferon preparations purified from human cell lines.
      METHODS: DNA samples were prepared from 75 commercial interferon preparations and
      analyzed for squirrel monkey retrovirus sequences by polymerase chain reaction
      and DNA sequencing. Since single polymerase chain reaction is not as sensitive, a
      nested polymerase chain reaction strategy was devised in order to detect squirrel
      monkey retrovirus-pol sequences. Amplification of beta-actin (human) sequences
      was used to confirm that samples contained human genomic DNA. To determine the
      authenticity of squirrel monkey retrovirus sequences, we analyzed amplified
      products by Southern blot hybridization and direct DNA sequencing.
      RESULTS/CONCLUSIONS: Thirty-nine samples were positive for squirrel monkey
      retrovirus-pol sequences by nested polymerase chain reaction. It is noteworthy
      that 29 samples were either weakly or very weakly positive by single polymerase
      chain reaction, thus stressing the importance of our sensitive polymerase chain
      reaction assay. However, it remains to be determined whether the residual DNA
      sequences detected by our sensitive nested polymerase chain reaction assay have
      biological consequences.

PMID- 9551677
TI  - The C282Y mutation in the haemochromatosis gene (HFE) and hepatitis C virus
      infection are independent cofactors for porphyria cutanea tarda in Australian
      patients.
AB  - BACKGROUND/AIM: Whether mutations in the putative haemochromatosis gene (HFE) and
      hepatitis C virus act independently to precipitate porphyria cutanea tarda is
      unknown. The aim of the study was to investigate the relationship between
      mutations in HFE, hepatitis C and porphyria cutanea tarda. METHODS: The
      frequencies of the C282Y and H63D mutations in HFE were determined in 27 patients
      with porphyria cutanea tarda and compared with the reported control frequencies.
      In addition, the presence of hepatitis C virus infection was identified and
      related to the patients' HFE status. RESULTS: The C282Y mutation was found in
      44.4% of patients compared with the control frequency of 12% (p<0.001). Three
      patients were homozygous for the C282Y mutation, two of whom did not meet current
      clinical diagnostic criteria for expressed haemochromatosis. The proportion of
      patients with the H63D mutation did not differ from the reported control
      frequency. The mean transferrin saturation and serum ferritin concentration were
      similar in porphyria cutanea tarda patients who were homozygous normal and
      heterozygous for the C282Y mutation, but greater in both groups than previously
      reported in healthy controls. Seven (25.9%) patients were anti-HCV IgG positive.
      None of these patients carried the C282Y mutation. Porphyria cutanea tarda
      patients heterozygous for the C282Y mutation and patients with anti-HCV
      antibodies had elevated transferrin saturations and serum ferritin
      concentrations. CONCLUSIONS: The raised frequency of the C282Y mutation in
      porphyria cutanea tarda indicates that this mutation is likely to be a
      predisposing factor. However, abnormalities of iron indices also exist in
      porphyria cutanea tarda patients without mutations in HFE. Hepatitis C virus
      infection is likely to be another common precipitating factor for porphyria
      cutanea tarda which acts independently of the C282Y mutation.

PMID- 9551678
TI  - Reduction in hepatic cytochrome P-450 is correlated to the degree of liver fat
      content in animal models of steatosis in the absence of inflammation.
AB  - BACKGROUND/AIM: Fatty liver has been associated with an increased risk of primary
      graft non-function and drug toxicity. However, these effects have been observed
      mainly in fatty liver with inflammation, a situation characterized by an overall
      reduction in cytochrome P-450 (CYP)-dependent activities as well as a contrasting
      increase in CYP2E1 activity. Our aim was to examine the impact of liver-fat
      accumulation on CYP in two animal models of fatty liver without
      necroinflammation. METHODS: Ducks were force-fed with a high-glucidic diet and
      male Wistar rats, after 48 h fasting, were refed a high-glucidic, fat-free diet
      for 48 h. Total CYP, aminopyrine- (AND), erythromycin-N-demethylase (END) and
      chlorzoxazone hydroxylase (CZOHase) activities as well as CYP2E1 and CYP3A
      proteins were quantified on microsomal proteins. RESULTS: Livers from force-fed
      ducks exhibited significant decreases in total CYP, AND, END and CZOHase
      activities, inversely correlated with fat-liver content. Refeeding male Wistar
      rats a high-glucidic, fat-free diet after 48 h fasting, resulting in a 235%
      increased liver fat content, was associated with a decrease in total CYP (55%),
      AND (78%), END (55%) and CZOHase (62%) activities as well as in CYP3A (70%) and
      CYP2E1 (80%) protein content. A significant inverse correlation was observed
      between CYP and total lipid content. CONCLUSIONS: In these models of steatosis
      induced by nutritional manipulations, fat liver accumulation was associated with
      a significant decrease in CYP activities and in CYP protein expression.
      Furthermore, the decreases in both CYP content and related activities were
      correlated with the degree of liver fat content.

PMID- 9551679
TI  - Rat liver transport and biotransformation of a cytostatic complex of bis
      cholylglycinate and platinum (II).
AB  - BACKGROUND/AIMS: Bile acids have previously been used as shuttles for directing
      organic drugs to the liver. The aim of this study was to investigate liver
      transport and biotransformation of a new cytostatic bioinorganic complex (Bamet
      H2), that was obtained by binding platinum(II) to two cholylglycinate moieties.
      METHODS: Using rat hepatocytes in primary culture, the kinetics of
      cholylglycinate, cisplatin and Bamet-H2 uptake were studied. Sodium-dependency of
      Bamet-H2 uptake was investigated by replacement of 116 mM NaCl by 116 mM choline
      chloride. Liver biotransformation was investigated by HPLC analysis of bile
      samples collected from anesthetized rats following intravenous Bamet-H2
      administration. Using isolated rat liver preparations, which were perfused with
      erythrocyte- and albumin-free Krebs-Henseleit solutions for 40 min, measurement
      of cholylglycinate, cisplatin and Bamet-H2 uptake and bile output was carried
      out. Interaction between Bamet-H2 and cholylglycinate for liver transport was
      studied by co-administration of 1 microM Bamet-H2 plus 500 microM cholylglycinate
      and 1 microM [14C]-cholylglycinate plus 500 microM Bamet-H2. RESULTS: Both
      cholylglycinate and Bamet-H2 uptake by rat hepatocytes followed saturation
      kinetics. Comparison between the two compounds indicated that the Vmax (22.2
      versus 8.5 nmol.5 min(-1).mg protein(-1)), and Kt (365 versus 171 microM) were
      higher for Bamet-H2 uptake. The efficiency of Bamet-H2 uptake (Vmax/Kt) was
      significantly reduced (-35%) in the absence of sodium. Cisplatin uptake by rat
      hepatocytes was approximately 10-fold lower than that for Bamet-H2 at any dose
      used. Moreover, this was not saturable up to 400 microM cisplatin. Bamet-H2 was
      not biotransformed during its intrahepatic residence in anesthetized rats. Bamet
      H2 uptake and secretion into bile by isolated rat livers exceeded cisplatin but
      were less than cholylglycinate. Differences between Bamet-H2 and cholylglycinate
      were more marked for bile output than for liver uptake. Thus, higher drug liver
      content was found after perfusion with Bamet-H2 than with cholylglycinate or
      cisplatin. Co-administration of Bamet-H2 and cholylglycinate revealed the
      existence of partial cross-inhibition in both liver uptake and bile output. Bamet
      H2 induced a more profound alteration on cholylglycinate uptake and bile
      secretion than cholylglycinate on both process for Bamet-H2. CONCLUSION: These
      results suggest that in the transfer of Bamet-H2 from the sinusoids to the
      canaliculi both bile acid and non-bile acid transport systems are involved.

PMID- 9551680
TI  - Bile duct bacterial isolates in primary sclerosing cholangitis: a study of
      explanted livers.
AB  - BACKGROUND/AIMS: The pathogenesis of the inflammatory lesion in primary
      sclerosing cholangitis is unknown. The clinical picture is characterized by i.a.
      episodes of fever, the cause of which also remains speculative. Previous studies
      of bacterial isolates in the liver or bile ducts in primary sclerosing
      cholangitis have had the shortcoming of possible contamination associated with
      the sampling. The aim of this study was to investigate whether bile and bile duct
      tissue, obtained under sterile conditions in connection with liver
      transplantation, contain bacteria. METHODS: We studied bile from bile duct walls
      and bile collected from the explanted livers of 36 patients with primary
      sclerosing cholangitis and 14 patients with primary biliary cirrhosis. RESULTS:
      Positive cultures were obtained from 21 of 36 primary sclerosing cholangitis
      patients, but from none of the primary biliary cirrhosis patients. The number of
      bacterial strains was inversely related to the time after the last endoscopic
      retrograde cholangiography. Treatment with antibiotics or intraductal stent, or
      the occurrence of fever before liver transplantation did not seem to influence
      the culture results, whereas antibiotic treatment in connection with endoscopic
      retrograde cholangiography may possibly have reduced the number of isolates in
      the cultures. Alpha-haemolytic Streptococci were retrieved as late as 4 years
      after the last endoscopic retrograde cholangiography. Retrospective analysis of
      liver laboratory tests after endoscopic retrograde cholangiography did not
      indicate a deleterious effect of the investigation. CONCLUSIONS: The data suggest
      that antibiotics should be given routinely in connection with endoscopic
      retrograde cholangiography. They also raise the question of a possible role of
      alpha-haemolytic Streptococci in the progression of primary sclerosing
      cholangitis.

PMID- 9551681
TI  - Mycobacterial DNA not detected in liver sections from patients with primary
      biliary cirrhosis.
AB  - BACKGROUND/AIMS: Recent studies in primary biliary cirrhosis have reported the
      detection of serum antibodies against Mycobacterium gordonae and of mycobacterial
      DNA in liver sections. The aim of this study was to investigate whether
      mycobacterial DNA is present in liver biopsy material in primary biliary
      cirrhosis. METHODS: Archival liver biopsy specimens from 11 patients with primary
      biliary cirrhosis (10 female, mean age 52 years) and 11 patients with autoimmune
      hepatitis (10 female, mean age 53 years) were identified. Positive control tissue
      comprised five archival lymph node specimens from patients with tuberculous
      lymphadenopathy, three of which had stained positive on ZN staining, and also a
      liver biopsy specimen from a patient with tuberculous hepatitis (ZN positive).
      Fixed sections were deparaffinised and DNA was extracted by mechanical disruption
      with glass beads. DNA was purified by use of diatoms and lysis in guanidinium
      thiocyanate in a technique previously validated for archival DNA. Primers were
      directed to amplify a partial 16S ribosomal RNA gene yielding the species
      specific character for mycobacteria, and also to amplify the constitutively
      expressed human gene GAPDH. RESULTS: The polymerase chain reaction was shown to
      be capable of detecting 1 fg of M. gordonae DNA in 'spiked' samples, equivalent
      to 1-5 bacterial cells. No mycobacterial DNA was detected in liver biopsy samples
      from either the primary biliary cirrhosis or autoimmune hepatitis groups. Of the
      tuberculous control sections, mycobacterial DNA was detected in four of five
      lymph nodes and the liver biopsy specimen. GAPDH amplification was detected in
      all tested samples from liver disease and tuberculous control samples.
      CONCLUSION: These data do not support a role for mycobacteria in the aetiology of
      primary biliary cirrhosis.

PMID- 9551682
TI  - Histopathological evaluation of liver fibrosis: quantitative image analysis vs
      semi-quantitative scores. Comparison with serum markers.
AB  - BACKGROUND/AIMS: Liver fibrosis is mainly evaluated by qualitative histological
      examination. Although histological semi-quantitative scores and quantitative
      determination with image analysis are now possible, these methods have not been
      fully validated and compared. Therefore, we evaluated these two methods
      prospectively in 243 patients with chronic liver disease. METHODS: The semi
      quantitative fibrosis score was evaluated by two independent pathologists, using
      the Knodell fibrosis score and a 6-grade score derived from the Metavir score;
      the area of fibrosis was measured by image analysis. The serum levels of
      hyaluronate, N-terminal peptide of procollagen III, laminin, transforming growth
      factor-beta1, alpha2-macroglobulin, apolipoprotein A1, PGA score and prothrombin
      index were measured. RESULTS: There was a good correlation between the semi
      quantitative fibrosis score and the area of fibrosis (r=0.84, p<10(-4)). Using
      multiple regression analysis, the semi-quantitative score was predicted by the 8
      serum markers with R2=0.69 (R2=0.59 for hyaluronate at the 1st step) while the
      area of fibrosis was predicted with R2=0.79 (R2=0.76 for hyaluronate at the 1st
      step), and the Knodell fibrosis score was predicted with R2=0.65 (R2=0.31 for
      hyaluronate at the 1st step). CONCLUSIONS: The area of fibrosis, as determined by
      image analysis, and the semi-quantitative score are well correlated. However, for
      serum markers the correlation is higher with the area of fibrosis than with the
      semi-quantitative score. Other characteristics such as reproducibility, rapidity,
      simplicity, adaptability, and exhaustiveness also favor image analysis.

PMID- 9551683
TI  - Upright posture decreases esophageal varices flow velocity in patients with
      cirrhosis.
AB  - BACKGROUND/AIMS: Patients with cirrhosis tend to have esophageal variceal
      bleeding episodes at night, rather than during the day time. Since human beings
      carry on ordinary activities in the upright posture in the day time and are
      recumbent at night, we hypothesized that posture may be a factor related to a
      circadian variation of variceal bleeding. The aim of this study was to examine
      the effect of upright posture on esophageal varices hemodynamics in patients with
      cirrhosis. METHODS: Nine patients with cirrhosis and esophageal varices were
      included in a crossover study performed on 2 separate days. On the non-endoscopic
      day, cardiac output, portal vein flow velocity, and superior mesenteric artery
      flow velocity were measured with percutaneous Doppler ultrasonography. Plasma
      renin activity and plasma norepinephrine concentrations were also determined. On
      the endoscopic day, in addition to the above measurements, esophageal varices
      flow velocity was measured using transesophageal Doppler ultrasonography. These
      measurements were performed in the supine position and 20 min after the
      assumption of the upright position. RESULTS: On the non-endoscopic day, the
      upright posture significantly decreased cardiac output, portal vein flow
      velocity, and superior mesenteric artery flow velocity. Plasma renin activity and
      plasma norepinephrine concentration were significantly increased after assumption
      of the upright position. On the endoscopic day, similar hemodynamic and hormonal
      changes were observed. In addition, the upright posture significantly decreased
      esophageal varices flow velocity. Furthermore, the magnitude of the reduction in
      esophageal varices flow velocity (-42%) was significantly greater than that in
      portal vein flow velocity (-22%, p<0.01) and that in superior mesenteric artery
      flow velocity (-25%, p<0.01). Although the change in esophageal varices flow
      velocity was not significantly correlated with that in plasma renin activity (r=
      0.28) and that in plasma norepinephrine concentration (r=-0.10), it was
      significantly correlated with the change in superior mesenteric artery flow
      velocity (r=0.73, p<0.05). CONCLUSIONS: The upright posture decreases esophageal
      varices flow velocity mainly because of the reduction in splanchnic blood flow.
      This effect may contribute to a low prevalence of esophageal variceal bleeding in
      the day time in patients with cirrhosis.

PMID- 9551684
TI  - Factors related to early mortality after transjugular intrahepatic portosystemic
      shunt for failed endoscopic therapy in acute variceal bleeding.
AB  - BACKGROUND: Uncontrolled variceal haemorrhage is the main indication for
      transjugular intrahepatic portosystemic shunt. However, mortality is 50% for this
      high-risk group. We have evaluated clinical and laboratory variables prior to
      transjugular intrahepatic portosystemic shunt in order to establish predictors of
      mortality, validated prospectively. METHOD: Over a 4-year period, 367 patients
      were admitted with variceal bleeding. In 54 patients endoscopic therapy for acute
      variceal bleeding failed and they had emergency transjugular intrahepatic
      portosystemic shunt. Failure of therapy was defined as continued bleeding after 2
      endoscopy sessions (n=39) or vasoconstrictor-resistant bleeding from
      gastric/ectopic varices (n=15). Thirty-three variables were analysed from data
      available immediately prior to transjugular intrahepatic portosystemic shunt.
      RESULTS: Twenty-six patients died within 6 weeks. In a multivariate analysis, 6
      factors had independent prognostic value: moderate/severe ascites, requirement
      for ventilation, white cell blood count (WBC), platelet count (PLT), partial
      thromboplastin time with kaolin (PTTK) and creatinine. A prognostic index (PI)
      score was derived, in which presence of moderate/severe ascites, or need for
      ventilation, scored 1: PI=1.54 (Ascites)+1.27 (Ventilation)+1.38 Ln (WBC)+2.48 ln
      (PTTK)+1.55 Ln (Creat)-1.05 Ln (PLT). Using this equation, 42% (n=10) of deaths
      occurred in the fifth quintile (PI > or = 18.52), where the mortality was 100%.
      The score was prospectively validated in a further 31 patients, giving 100%
      positive predictive value. Eleven further patients died, including all seven with
      a PI >18.5. No survivors had a PI >18.3. CONCLUSION: Despite immediate control of
      bleeding by transjugular intrahepatic portosystemic shunt, patients with
      uncontrolled variceal haemorrhage have a high mortality, particularly when
      associated with markers of advanced liver disease, sepsis and multi-organ
      failure. The use of transjugular intrahepatic portosystemic shunt is probably not
      justified in this subgroup. Our prognostic index can help identify such patients,
      and, if validated elsewhere, will help in deciding when to use transjugular
      intrahepatic portosystemic shunt.

PMID- 9551685
TI  - Differential effects of exogenous and endogenously generated H2O2 on phagocytic
      activity and glucose release of normal and cirrhotic livers.
AB  - BACKGROUND/AIMS: Reactive oxygen species play an essential role in necro
      inflammatory processes. Therefore, the aim of the present studies was to
      investigate the effect of exogenous and endogenously produced H2O2 on the
      phagocytic capacity and glucose release of perfused cirrhotic rat livers in
      comparison with that on the controls. METHODS: Complete septal cirrhosis was
      achieved by oral treatment of rats with thioacetamide for 6 months. The
      phagocytic capacity of the perfused livers was measured by the uptake of
      colloidal carbon. During the continuous perfusion with colloidal carbon, either
      H2O2 or benzylamine was added to the perfusion medium for a limited time period.
      The latter functioned as an endogenous H2O2 donor. RESULTS: In control rats
      exogenous and endogenously produced H2O2 caused a transient stimulation of the
      hepatic colloidal carbon uptake as well as of the glucose release. Inhibition of
      the catalase by aminotriazol doubled the changes evoked by H2O2, whereas blockade
      of the Kupffer cells by GdCl3 drastically reduced its stimulatory effect.
      Cirrhotic livers took up less colloidal carbon and released lower amounts of
      glucose than the controls when stimulated by exogenous H2O2. The inhibition of
      the nitric oxide synthetase augmented the H2O2-induced effect in controls as well
      as in the cirrhotic livers by 250% and 620% (colloidal carbon uptake) and 340%
      and 760% (glucose release), respectively. The blockade of the eicosanoid
      production by indomethacin and caffeic acid drastically increased the glucose
      release and the colloidal carbon uptake in controls and, in absolute terms, to a
      lesser extent in cirrhotic livers. Endogenous H2O2 produced by the addition of
      benzylamine stimulated the colloidal carbon uptake and glucose release in livers
      from both groups. The inhibition of the lipoxygenase increased both parameters,
      whereas different effects were elicited by the addition of superoxide dismutase
      in controls and cirrhotic livers. CONCLUSION: The maximum uptake of colloidal
      carbon and glucose release, measured after stimulation by H2O2, was lower in
      cirrhotic livers than in controls, thus indicating a lowered phagocytic capacity
      of Kupffer cells and altered glycogenolytic response of the hepatocytes in
      cirrhotic livers. The use of various effectors provided evidence that superoxide
      anions, nitric oxide and, possibly, arachidonic acid are involved in the signal
      transduction between Kupffer cells and hepatocytes when stimulated by exogenous
      or endogenously produced H2O2. This signalling mechanism seems to be impaired in
      cirrhotic livers.

PMID- 9551686
TI  - Interferon gamma treatment prevents procollagen gene expression without affecting
      transforming growth factor-beta1 expression in pig serum-induced rat liver
      fibrosis in vivo.
AB  - BACKGROUND/AIM: The aim of this study was to investigate the effect of interferon
      gamma on the synthesis of matrix proteins such as collagens with the relation to
      transforming growth factor-beta1 expression in vivo. METHODS: We investigated the
      effects of interferon gamma in a model of liver fibrosis induced by pig serum in
      male Wistar rats, which develops fibrosis without an increase in serum alanine
      aminotransferase (i.e., without hepatocyte injury). Rats were injected with 0.5
      ml of pig serum twice a week for 8 weeks with or without 20,000 or 50,000 U of
      interferon gamma. RESULTS: Interferon gamma at doses up to 50,000 U/day prevented
      fibrosis, as indicated by reduced hydroxyproline content in the liver. Interferon
      gamma at 50,000 U/day also reduced expression of type I and III procollagen in
      the liver. However, the expression of transforming growth factor-beta1 mRNA and
      protein in the liver was not reduced by interferon gamma. Histologically,
      interferon gamma at 50,000 U/day also reduced the number of myofibroblast-like
      cells (activated stellate cells). CONCLUSIONS: These results indicate that
      interferon gamma can prevent fibrosis by inhibiting the activation and
      proliferation of stellate cells, resulting in reduced expression of procollagen
      without affecting transforming growth factor-beta1 expression in pig serum
      induced rat liver fibrosis in vivo.

PMID- 9551687
TI  - Long-term cultures of human fetal liver cells: a three-dimensional experimental
      model for monitoring liver tissue development.
AB  - BACKGROUND/AIMS: The present study describes an embryonic-fetal liver culture
      system which allows morphogenetic interactions consistent with the development of
      the hepatocellular function. METHODS: Intact livers from 8-12-week embryos were
      soaked in an extracellular matrix at 4 degrees C and gently dissociated without
      any enzymatic treatment. The resulting spherical hepatic units were cultured in a
      chemically defined serum-free medium and seeded into an extracellular matrix
      layer. Adherent three-dimensional tissue specimens were examined at various times
      by light and electron microscopy to evaluate the maintenance of hepatocyte
      morphology. RESULTS: The liver cells were viable for over 4 months;
      erythropoietic burst colonies were detected for longer than 6 weeks. Parallel
      detection of bile salt production in the medium by high performance liquid
      chromatography proved liver tissue functionality. Bile salt composition revealed
      predominance of taurine-conjugates rather than glycine. Maximum bile salt
      concentration (approximately 3 months) coincided with structural and
      ultrastructural observations indicating a marked decline in hematopoiesis, well
      defined biliary canaliculi and formation of an organ-like structure. CONCLUSIONS:
      This three-dimensional culture system recapitulates fetal liver development with:
      (i) initial proliferation of both fetal erythropoietic and hepatic cells and (ii)
      subsequent shut-off of erythropoiesis and a shift to a more advanced stage of
      hepatocyte function, such as bile salt secretion.

PMID- 9551688
TI  - Diagnostic value and tolerance of Lipiodol-computed tomography for the detection
      of small hepatocellular carcinoma: correlation with pathologic examination of
      explanted livers.
AB  - BACKGROUND/AIMS: This study aimed to assess the tolerance and the real
      sensitivity of Lipiodol-computed tomography in the detection of small
      hepatocellular carcinoma by comparison with pathological examination of the
      explanted livers. METHODS: Seventy-two patients with cirrhosis (Child A=8, B=36,
      C=28) awaiting orthotopic liver transplantation underwent Lipiodol-computed
      tomography to determine the presence, number and location of possible
      hepatocellular carcinoma nodules. Before liver transplantation six patients had a
      presumed single hepatocellular carcinoma diagnosed by biopsy. Liver
      transplantation was performed a mean of 6 months after Lipiodol-computed
      tomography. Explanted livers were sectioned at 0.8- to 1-cm intervals. Lipiodol
      computed tomography staging and pathologic findings were compared. RESULTS:
      Pathologic studies showed 24 hepatocellular carcinoma nodules (diameter, 2-42 mm)
      not diagnosed before liver transplantation in 14 of the 72 livers. Lipiodol
      computed tomography detected 6 of these 24 nodules, but none of the daughter
      lesions (n=9) in the six patients with a presumed single hepatocellular
      carcinoma. Lesion-by-lesion analysis revealed a sensitivity of 37%. Lipiodol
      computed tomography falsely detected three additional nodules not confirmed by
      pathologic examination (1 haemangioma, 2 nondysplastic regenerating nodules). One
      Child C patient developed variceal bleeding within 2 days after injection of
      Lipiodol. CONCLUSIONS: Tolerance of this procedure was satisfactory, even in
      Child C patients. Lipiodol-computed tomography has a low sensitivity in the
      detection of small hapatocellular carcinoma. These results must be considered
      when liver resection or liver transplantation is proposed for the treatment of
      hepatocellular carcinoma.

PMID- 9551689
TI  - Preoperative TNM-classification is a better prognostic indicator for recurrence
      of hepatocellular carcinoma after liver transplantation than albumin mRNA in
      peripheral blood. Liver Transplant Oncology Group.
AB  - BACKGROUND/AIM: Survival after orthotopic liver transplantation for
      hepatocellular carcinoma is limited by a high rate of tumor recurrence. A
      polymerase chain reaction assay based on the detection of albumin mRNA expression
      in peripheral blood for detection of hematogenous micrometastasis of
      hepatocellular carcinoma has been described, which may help to select candidates
      for orthotopic liver transplantation. METHODS: The prognostic value of a highly
      sensitive nested reverse transcription-polymerase chain reaction assay was
      evaluated in comparison with the TNM-classification of the International Union
      against Cancer in a population of liver transplant candidates. RESULTS: Eighty
      patients with liver disease and 42 control patients were evaluated. Six of 21
      patients with hepatocellular carcinoma and 11 of 59 patients with other diseases
      of the liver were positive for albumin reverse transcription-polymerase chain
      reaction, making this assay an indicator of ongoing liver damage without absolute
      specificity for hepatocellular carcinoma. Twelve patients with hepatoma were
      followed after liver transplantation and seven of those patients had a tumor
      recurrence within 12 months. Six of these patients with recurrence had
      International Union against Cancer stage IV A tumors preoperatively, while only
      one of them was positive for albumin reverse transcription-polymerase chain
      reaction before transplantation. Only one patient with a stage I to III tumor had
      a recurrence within 12 months. CONCLUSIONS: Detection of albumin mRNA in
      peripheral blood by reverse transcription-polymerase chain reaction seems to be
      an unreliable marker for assessing hematogenous spread of hepatocellular
      carcinoma. With International Union against Cancer stage IV A being a much better
      predictor of tumor recurrence, the practical value of albumin mRNA reverse
      transcription-polymerase chain reaction for patient selection in liver transplant
      candidates seems to be very limited.

PMID- 9551690
TI  - Antitumor effect of the nucleoside analogs 2-chlorodeoxyadenosine and 2',2'
      difluorodeoxycytidine on human hepatoma HepG2 cells.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most malignant tumors in
      the world. Although a wide range of therapeutic options is available, the
      efficacy of these methods and the prognosis of hepatocellular carcinoma are still
      very poor. The nucleoside analogs 2-chlorodeoxyadenosine (Cladribine, 2-CdA) and
      2',2'-difluorodeoxycytidine (Gemcitabine, dFdC) have shown potent cytotoxic
      effects on various human tumor cell lines in vitro and marked therapeutic
      efficacy in the treatment of lymphoproliferative disorders and several solid
      tumors in vivo. In the present study we evaluated the antitumor effect of 2-CdA
      and dFdC on human hepatoma HepG2 cells. METHODS: HepG2 cells were grown in the
      absence and presence of increasing concentrations of 2-CdA and dFdC. Antitumor
      activity was assessed by inhibition of cell growth, evaluated by counting cell
      numbers in a hemocytometer and by 3H-thymidine uptake, and by reduction of cell
      viability as determined by exclusion of 0.1% trypan blue. For rescue experiments,
      the natural pyrimidine deoxycytidine (dCyd) was added simultaneously or delayed.
      RESULTS: A strong antitumor activity was observed for both compounds. dFdC showed
      a more pronounced effect with an inhibition constant (IC50) of 3.98+/-0.03 nM in
      comparison to 2-CdA with an IC50 of 16.66+/-0.40 nM. Both drugs achieved their
      half-maximal antitumor activity after 31 h. With respect to dFdC, fractionated
      daily administrations showed a distinctly greater antitumor activity than a
      single transient administration. The cytotoxic effects of 2-CdA and dFdC were
      completely reversed by simultaneous addition of dCyd. CONCLUSION: In this paper
      we show strong antitumor effects of the nucleoside analogs 2-CdA and dFdC on the
      human hepatoma cell line HepG2. These findings suggest that both compounds, but
      in particular dFdC, are promising substances for further evaluations in the
      treatment of hepatocellular carcinoma.

PMID- 9551691
TI  - Transient emergence of hepatitis B variants in a patient with chronic hepatitis B
      resistant to lamivudine.
AB  - BACKGROUND: Lamivudine is a cytosine nucleoside analogue that inhibits hepatitis
      B virus replication. Resistance to lamivudine monotherapy has been reported in
      patients who received lamivudine to prevent recurrent hepatitis B virus infection
      after liver transplantation. No cases of resistance have been described in
      patients who did not clear HBV DNA during lamivudine therapy. METHODS: We report
      the case of an adult patient with chronic HBeAg-positive hepatitis B who had a
      hepatitis flare during lamivudine therapy. The patient did not respond to
      lamivudine and, at 4 months of treatment, developed a significant serum alanine
      aminotransferase elevation. Alanine aminotransferase levels remained elevated for
      4 months and returned to baseline spontaneously. Lamivudine therapy was
      administered for 1 year (52 weeks) and after withdrawal, alanine aminotransferase
      levels remained elevated. RESULTS: Sequencing studies of HBV DNA at week 52
      showed the emergence of a lamivudine-resistant variant associated with two point
      mutations in the hepatitis B virus polymerase gene: one mutation led to amino
      acid substitution of methionine to valine at residue 552, in the highly conserved
      tyrosine-methionineaspartate-aspartate motif, part of the active site of the
      polymerase; the second mutation consisted of a substitution of leucine to
      methionine at residue 528. At week 54 of follow-up, both mutations were
      undetectable. CONCLUSION: This observation demonstrates the transient emergence
      of HBV variants in the course of therapy in a patient resistant to lamivudine
      therapy.

PMID- 9551692
TI  - Insulin-dependent diabetes mellitus during alpha-interferon therapy for chronic
      viral hepatitis.
AB  - A 29-year-old man was observed to develop insulin-dependent diabetes mellitus
      following a 5-month treatment with recombinant alpha-2b-interferon for chronic
      hepatitis C. After the onset of the disease, serum samples that had,
      respectively, been collected before therapy commencement, at month 3, and at the
      onset of insulin-dependent diabetes mellitus were tested for islet-cell (ICA
      IgG), glutamic acid decarboxylase (GAD-Abs), IA2 (IA2-Abs) and insulin (IA-Abs)
      autoantibodies. The following results were obtained: ICA-IgG, 5, >80, and >80 JDF
      U, respectively; GAD-Abs: >100 U/ml in all three measurements; IA2-Abs and IA
      Abs: negative. During treatment, thyroid microsomal autoantibodies increased
      markedly (from 1:100 to 25,600 titer); thyroid-stimulating hormone was
      persistently normal. HLA class II typing revealed a genetic predisposition to
      insulin-dependent diabetes mellitus as demonstrated by the presence of DRB1*
      04/08, DQ A1 52 Arg+/Arg+, and DQB1 57 N-Asp/Asp alleles. One year after the
      onset of insulin-dependent diabetes mellitus, the patient is still receiving 30
      IU insulin daily; the liver function tests are normal and HCV-RNA is negative.
      These data support the hypothesis that, in predisposed patients, alpha-interferon
      therapy can enhance an ongoing autoimmune process against pancreatic beta-cells
      and induce overt insulin-dependent diabetes mellitus. We therefore suggest that,
      in patients with a documented predisposition to insulin-dependent diabetes
      mellitus, alpha-IFN therapy should be administered with caution.

PMID- 9551693
TI  - Cerebral aspergillosis in a liver transplant recipient: a case report of long
      term survival after combined treatment with liposomal amphotericin B and surgery.
AB  - Cerebral aspergillosis is a life-threatening complication in liver transplant
      recipients, with mortality rates approaching 100%; treatment with amphotericin B
      is of limited efficacy because of its poor distribution in the cerebrospinal
      fluid and its systemic side effects. We report the case of a liver transplant
      recipient who developed recurrent cerebral Aspergillus fumigatus infection, and
      was successfully treated by combined surgical excision of the lesion and
      administration of liposomal amphotericin B. This first report of long-term
      complication-free survival in a liver transplant recipient suggests that therapy
      with liposomal amphotericin B may reduce the risk of recurrence of cerebral
      aspergillosis in these immunocompromised patients.

PMID- 9551694
TI  - Images in hepatology: Hepatic iron in hemochromatosis enhances hepatocellular
      carcinoma in magnetic resonance imaging.

PMID- 9551695
TI  - Risk factors for acute hepatitis A in Italy: possible pitfalls of a disease
      registry-based case-control study.

PMID- 9551696
TI  - Successful treatment of polyarteritis nodosa related to hepatitis B virus with
      interferon alpha as first-line therapy.

PMID- 9551697
TI  - Ischaemic left ventricular dysfunction: a preventable precursor of heart failure?

PMID- 9551698
TI  - Current therapeutic uses and potential of beta-adrenoceptor agonists and
      antagonists.
AB  - Beta-adrenoceptors are members of a large family of hormone and neurotransmitter
      receptors that initiate their biological function by coupling to GTP-binding
      regulatory proteins. beta-Adrenoceptors can be subdivided into two main
      subgroups, designated beta1 and beta2. Atypical beta-adrenoceptors or beta3
      adrenoceptors, which are present on adipocytes, have been demonstrated
      pharmacologically. Their function in adipose tissue is currently being
      investigated. Beta2-adrenoceptor agonists have played a key role in the treatment
      of asthma for some 30 years, being used for the relief and prophylaxis of
      symptoms. There is, however, no evidence that tolerance to the bronchodilator or
      anti-bronchoconstrictor effects of these drugs is responsible for the deleterious
      effects reported with the regular use of bronchodilators. In neuropsychiatry,
      beta-adrenoceptor antagonists have been used for the treatment of acute stress
      reactions and generalised anxiety, essential tremor and prophylaxis of migraine.
      In general, they are effective in anxiety disorders if the somatic symptoms are
      not extreme. For prophylactic treatment of migraine, beta-adrenoceptor
      antagonists such as propranolol, metoprolol, nadolol and atenolol are the drugs
      of first choice. In cardiology, beta-adrenoceptor antagonists are an important
      class for the treatment of high blood pressure, arrhythmias and angina pectoris,
      and for prevention of myocardial infarction. With chronic treatment, they reduce
      mortality in hypertension and prolong survival in patients with coronary heart
      disease.

PMID- 9551699
TI  - The effect of Y-25510 injection on the serum levels of some cytokines in healthy
      adult volunteers.
AB  - OBJECTIVE: Y-25510 was administered by means of an intravenous drip infusion to
      healthy adult male volunteers at a dose of 40, 80 or 160 mg in a single-dose
      study, and at a dose of 160 mg once a day for 7 days in a multiple-dose study.
      RESULTS: Serum levels of interleukin (IL)-1beta, IL-6 and IL-10 were
      significantly increased, but there was no change in leukocyte and platelet
      counts. The peak serum concentration of IL-1beta was nearly maximum at the single
      doses of 40 and 80 mg, and at the multiple dose of 160 mg per day. The peak serum
      concentration of IL-6 increased in a dose-dependent manner at a dose of 40 mg or
      more. For the multiple-dose study, the serum level of IL-10, which remained
      unchanged in the placebo group, began to increase in the Y-25510 group following
      the maximum serum level of IL-1beta and IL-6. There were no clinically relevant
      differences in body temperature and blood pressure after the administration of Y
      25510. CONCLUSION: These findings that leukocyte and platelet counts never
      increased, despite the increment of the IL-1beta and IL-6 production after the
      administration of Y-25510, may be explained in part by the negative feedback
      mechanism induced by IL-10.

PMID- 9551700
TI  - Adjunctive lamotrigine therapy in patients with refractory seizures: a lifetime
      cost-utility analysis.
AB  - OBJECTIVE: Lamotrigine as add-on treatment (500 mg per day) is effective in
      patients with refractory epilepsy, but its high cost requires a pharmacoeconomic
      analysis. We conducted a retrospective lifetime cost utility study in which
      clinical data were derived from a recent placebo-controlled clinical trial, cost
      of-illness data were drawn from a previous ad-hoc study, and quality-of-life
      values were obtained by prospectively interviewing a separate group of 81
      patients referred to our institution with epilepsy. RESULTS: Our analysis showed
      that chronic lamotrigine treatment implies an incremental lifetime cost of about
      $1,600,000 for every 100 patients. Incremental lifetime utility was around 40
      quality-adjusted life-years (QALYs) for every 100 patients. On the basis of these
      data, adjunctive lamotrigine was estimated to cost approximately $41,000 per QALY
      gained. Sensitivity testing suggested a range of $25,000-$85,000 per QALY gained.
      CONCLUSION: Adjunctive lamotrigine (500 mg per day) in refractory epilepsy seems
      to have a worse pharmacoeconomic profile than many pharmacological treatments
      commonly used in areas other than epilepsy. Further data are needed to determine
      if lamotrigine can be equally effective at lower (and less costly) daily doses
      which could markedly improve its pharmacoeconomic characteristics.

PMID- 9551701
TI  - Pharmacokinetics of glibenclamide and its metabolites in diabetic patients with
      impaired renal function.
AB  - BACKGROUND: Glibenclamide (Gb) may provoke long-lasting hypoglycaemic reactions,
      and one of the known risk factors is impaired renal function. We have
      demonstrated Gb to have a terminal elimination half-life of 15 h, and the main
      metabolites have a hypoglycaemic effect. With few exceptions, detailed studies on
      second generation sulphonylureas in diabetics with impaired renal function are
      lacking. Therefore, we analysed the pharmacokinetics of Gb and its active
      metabolites, 4-trans-hydroxyglibenclamide (M1) and 3-cis-hydroxy-glibenclamide
      (M2) in this patient group. METHODS: Two groups of 11 diabetic patients with
      impaired renal function (IRF, iohexol clearance range 7-42 ml.min(-1) . 1.73 m(
      2)) or normal renal function (NRF, iohexol clearance range 75-140 ml.min(-1) .
      1.73 m(-2)) were compared. A single oral 7-mg dose of Gb was administered after
      overnight fasting. Serum samples and urine collections were obtained over 48 h
      and 24 h, respectively. Concentrations of Gb, M1 and M2 were determined by a
      sensitive and selective high-performance liquid chromatography assay. RESULTS:
      Peak serum values of M1 (24-85 ng.ml(-1) vs 16-57 ng.ml(-1)), M2 (7-22 ng.ml(-1)
      vs <5-18 ng.ml(-1)) and M1 + M2 (32-100 ng.ml(-1) vs 23-76 ng.ml(-1)) were higher
      in the IRF group. AUC and Cmax of Gb were lower and the clearance to
      bioavailability ratio (CL/f) was higher in the IRF group. AUC and Cmax of M1 were
      higher and CL/f lower in the IRF group. Much lower amounts of M and M2 were
      excreted in the urine in the IRF group (7.2% vs 26.4% in 24 h). The fraction of
      the Gb dose excreted as metabolites (fe(met) 0-24 h), ranged between 0.005 and
      0.36 and correlated significantly with renal function measured by iohexol
      clearance. No other pharmacokinetic differences were found. CONCLUSION: The
      differences in AUC, Cmax and CL/f of Gb may be explained by a higher free
      fraction in the IRF group which would increase Gb metabolic clearance. The
      inverse findings regarding M1 may be explained by the fact that the metabolites
      are primarily eliminated by the kidneys. After a single dose of Gb, neither Gb,
      M1 nor M2 seemed to accumulate in diabetic subjects with IRF. As only small
      amounts of M1 and M2 were excreted in the urine, this indicates one or several
      complementary non-renal elimination routes, e.g. shunting of metabolised Gb to
      the biliary excretion route and/or enterohepatic recycling of both metabolites
      and unmetabolised Gb.

PMID- 9551702
TI  - Pharmacokinetics of low doses of methotrexate in patients with psoriasis over the
      early period of treatment.
AB  - OBJECTIVE: The aim of the present study was to investigate the pharmacokinetics
      and pharmacodynamics of low-dose methotrexate (MTX) in the early phase (3 months)
      after the start of antipsoriatic therapy. METHODS: Ten male and female psoriatic
      patients who failed to respond to previous conventional therapy were treated with
      15 mg oral MTX once per week. The pharmacokinetics in plasma and the urinary
      excretion of MTX and 7-hydroxymethotrexate (7-OH MTX) were investigated after
      doses 1, 5 and 13 (corresponding to phases I, II and III, respectively). On the
      same occasions, MTX accumulation in erythrocytes obtained before MTX
      administration was investigated. Pharmacodynamics of MTX were evaluated using the
      psoriasis area and severity index (PASI) score. RESULTS: There were marked
      intersubject differences (range of coefficients of variation 34.9-76.3%) in the
      area under the curve (AUC), peak concentration (Cmax) and clearance (CL) of MTX.
      Total CL was proportional to renal clearance (CLR) (r2 = 0.735, P < 0.0001) which
      accounted for 73 (19)% of the former. There was a strong linear relationship (r2
      = 0.819, P < 0.0001) between CL of MTX and creatinine clearance. Within 48 h of
      drug administration, the urinary excretion of MTX was 46-99% of the dose, while
      that of 7-OH MTX was 1.5-8.6%. In 8 of 10 patients, more than 70% of the MTX dose
      was recovered. No intraindividual variations of MTX kinetic parameters during
      treatment were observed. MTX concentrations in erythrocytes reached the steady
      state concentration in the range 40.7-170 nmol.l(-1) after 2 months of therapy.
      Pharmacodynamic measurement versus pharmacokinetics revealed a significant
      inverse relationship between PASI score and MTX AUC (rs = -0.912, P < 0.002) and
      between PASI score and erythrocytic MTX (rs = -0.988, P < 0.002). CONCLUSION: The
      relationship between MTX pharmacokinetics (AUC or erythrocytic MTX) and
      pharmacodynamics (PASI score) may exist. It is likely that the efficacy of
      psoriasis therapy with MTX could be improved by adjusting the dose according to
      plasma concentrations obtained after the first MTX administration.

PMID- 9551704
TI  - An interaction study with cimetidine and the new angiotensin II antagonist
      valsartan.
AB  - OBJECTIVE: This was a randomised, open, three-way crossover study in 12 healthy
      male volunteers to determine the effect of a single oral dose of cimetidine on
      the pharmacokinetics of a single oral dose of the angiotensin II receptor
      antagonist valsartan and vice versa. The volunteers received either valsartan
      alone (160 mg), or cimetidine alone (800 mg), or valsartan 1 h after cimetidine.
      The study was designed primarily to detect a possible influence of cimetidine on
      the rate and extent of absorption of valsartan. METHODS: Plasma concentrations of
      valsartan and cimetidine, measured by means of high-performance liquid
      chromatography, were used to calculate pharmacokinetic parameters. The rate of
      absorption of valsartan and the fraction of the dose absorbed and systemically
      available after oral administration were calculated using data from an i.v. study
      with valsartan in healthy young volunteers. RESULTS: The pharmacokinetics of
      cimetidine area under curve (AUC0-48 h), maximum concentration (Cmax), time to
      reach Cmax(tmax) and apparent terminal plasma half-life (t1/2) was not changed by
      co-administration of valsartan. For valsartan, the AUC0-48 h increased by 7% and
      the Cmax by 51% (ratio of geometric means) with co-administration of cimetidine.
      The higher value for Cmax was attributed to the initial increase in the rate of
      absorption of valsartan: ka was increased 2.7-fold and another indicator for the
      rate of absorption, Cmax/tmax, 2.2-fold. This effect was ascribed to inhibition
      of acid secretion by cimetidine, which leads to a higher gastric pH, thereby
      increasing the solubility of valsartan; the t1/2 of valsartan was not changed.
      After valsartan alone, 19% of the dose was absorbed, 23% with co-administration
      of cimetidine. It was estimated that only 2.2% of the possible change in AUC
      might be missed by giving a single high dose of cimetidine instead of multiple
      doses, with the aim to optimally inhibit formation of the inactive metabolite of
      valsartan. Cimetidine-related changes in the rate of elimination of valsartan
      were not anticipated, since the clearance from plasma occurs mainly by biliary
      excretion of unchanged valsartan; metabolism and renal excretion are only minor
      contributors. Therefore, even in the clinically relevant situation with multiple
      doses of valsartan and cimetidine, notable changes in the pharmacokinetics of
      valsartan, except for an increase in Cmax, are not to be expected. This increase
      in Cmax appears to be of no clinical significance. Valsartan alone and in
      combination with cimetidine was well tolerated by healthy subjects.

PMID- 9551703
TI  - Fluconazole but not itraconazole decreases the metabolism of losartan to E-3174.
AB  - OBJECTIVE: Losartan is metabolised to its active metabolite E-3174 by CYP2C9 and
      CYP3A4 in vitro. Itraconazole is an inhibitor of CYP3A4, whereas fluconazole
      affects CYP2C9 more than CYP3A4. We wanted to study the possible interaction of
      these antimycotics with losartan in healthy volunteers. METHODS: A randomised,
      double-blind, three-phase crossover study design was used. Eleven healthy
      volunteers ingested orally, once a day for 4 days, either itraconazole 200 mg,
      fluconazole (400 mg on day 1 and 200 mg on days 2-4) or placebo (control). On day
      4, a single 50-mg oral dose of losartan was ingested. Plasma concentrations of
      losartan, E-3174, itraconazole, hydroxy-itraconazole and fluconazole were
      determined over 24 h. The blood pressure and heart rate were also recorded over
      24 h. RESULTS: The mean peak plasma concentration (Cmax) and area under the curve
      [AUC(0-infinity)] of E-3174 were significantly decreased by fluconazole to 30%
      and to 47% of their control values, respectively, and the t1/2 was increased to
      167%. Fluconazole caused only a nonsignificant increase (23-41%) in the AUC and
      t1/2 of the unchanged losartan. Itraconazole had no significant effect on the
      pharmacokinetic variables of losartan or E-3174. The ratio AUC(0-infinity)(E
      3174)/AUC(0-infinity)losartan was 60% smaller during the fluconazole than during
      the placebo and itraconazole phases. No clinically significant changes in the
      effects of losartan on blood pressure and heart rate were observed between
      fluconazole, itraconazole and placebo phases. CONCLUSION: Fluconazole but not
      itraconazole interacts with losartan by inhibiting its metabolism to the active
      metabolite E-3174. This implicates that, in man, CYP2C9 is a major enzyme for the
      formation of E-3174 from losartan. The clinical significance of the fluconazole
      losartan interaction is unclear, but the possibility of a decreased therapeutic
      effect of losartan should be kept in mind.

PMID- 9551705
TI  - Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after
      inhaled administration.
AB  - OBJECTIVE: To evaluate the pharmacokinetic and systemic pharmacodynamic
      properties of inhaled fluticasone propionate (FP). METHODS: Single doses of 0.25,
      0.5, 1.0 and 3.0 mg FP were administered to groups of six healthy subjects. Serum
      concentration profiles of FP were monitored over 24 h by means of high
      performance liquid chromatography/mass spectrometry (HPLC/MS-MS). Systemic
      pharmacodynamic effects were evaluated by measuring endogenous serum cortisol and
      circulating white blood cells, and analyzed with previously developed integrated
      pharmacokinetic/pharmacodynamic (PK/PD) models. RESULTS: FP showed a dose
      independent terminal half-life with a mean (SD) of 6.0 (0.7) h. Maximum serum
      concentrations occurred 1.0 (0.5) h after administration, ranging from 90 pg.ml(
      1) for the 0.25 mg dose to 400 pg.ml(-1) for the 3.0 mg dose. This, together with
      an estimated mean absorption time of nearly 5 h and a known oral bioavailability
      of less than 1%, indicates prolonged residence at and slow absorption from the
      lungs. In the investigated dose range, the cumulative systemic effect was dose
      dependent for both markers of pharmacodynamic activity. For doses of 0.25, 0.50,
      1.0 and 3.0 mg FP, the PK/PD-based cumulative systemic-effect parameters were
      159, 186, 257 and 372% .h for lymphocyte suppression, 107, 186, 202 and 348% .h
      for granulocyte induction and 23.6%, 33.8%, 51.0% and 73.6% for cortisol
      reduction, respectively. The time courses of lymphocytes, granulocytes and
      endogenous cortisol could be sufficiently characterized with the applied PK/PD
      models. The measured in vivo EC50 values, 30 pg.ml(-1) and 7.3 pg.ml(-1) for
      white blood cells and cortisol, respectively, were in good agreement with
      predictions based on the in vitro relative receptor affinity of FP. CONCLUSION:
      After inhalation, FP follows linear pharmacokinetics and exhibits dose-dependent
      systemic pharmacodynamic effects that can be described by PK/PD modeling.

PMID- 9551706
TI  - Influence of erythromycin pre- and co-treatment on single-dose pharmacokinetics
      of the HMG-CoA reductase inhibitor cerivastatin.
AB  - OBJECTIVE: Cerivastatin is a novel, synthetic, highly potent 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that effectively reduces
      serum cholesterol levels at very low doses. It is exclusively cleared from humans
      via cytochrome P450-mediated biotransformation (demethylation M1; hydroxylation
      M23) and subsequent biliary/renal excretion of the metabolites. The influence of
      concomitant administration of erythromycin, a potent CYP3A4 inhibitor, on
      cerivastatin bioavailability and pharmacokinetics was investigated. METHODS:
      Twelve healthy young male subjects received single oral doses of 300 microg
      cerivastatin alone or on the 4th day of a 4-day pre- and co-treatment with
      erythromycin 500 mg t.i.d. in a randomised, non-blind crossover study. Plasma and
      urine samples were analysed for cerivastatin and its major metabolites by
      validated specific high-performance liquid chromatography assays. RESULTS:
      Cerivastatin was safe and well tolerated. No clinically relevant treatment
      emergent changes in laboratory parameters were observed. The pre- and co
      treatment with erythromycin 500 mg t.i.d. had a modest influence on cerivastatin
      clearance, leading to a mean increase in the maximum plasma concentration (Cmax)
      of 13% and a slightly increased terminal half-life (approximately 10%), resulting
      in a mean elevation of the area under the curve (AUC) of 21%; time to peak (tmax)
      remained unchanged. While the mean AUC of the metabolite M1 following the
      combined dosing was decreased by 60% compared with mono-dosing, the mean AUC of
      M23 exhibited an increase of approximately 60%. The respective Cmax results
      paralleled these pronounced effects, whereas the influence on mean terminal half
      lives was small (i.e. for M23, an approximate 20% increase) or not observable
      (i.e. for M1). CONCLUSIONS: Concomitant administration of erythromycin 500 mg
      t.i.d. affects, to a certain extent, the metabolism of cerivastatin, administered
      as a single oral dose of 300 microg, resulting in a slightly increased exposure
      of the parent drug and active metabolites which, however, does not need dose
      adjustment. In addition, the small increase in cerivastatin half-life does not
      predict an accumulation beyond steady state. The pharmacokinetic data for the
      major metabolites suggest that the M1 metabolic pathway is more sensitive to
      CYP3A4 inhibition than the parallel M23 pathway, supporting recent in vitro
      findings that further cytochrome P450 isozymes are differently involved in the
      metabolic pathways of cerivastatin.

PMID- 9551707
TI  - Cimetidine does not alter atorvastatin pharmacokinetics or LDL-cholesterol
      reduction.
AB  - OBJECTIVE: To determine the effects of cimetidine on the steady-state
      pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxymethyl-glutaryl
      coenzyme A (HMG-CoA) reductase inhibitor. METHODS: Twelve healthy subjects
      participated in a randomized two-way crossover study. Each subject received
      atorvastatin 10 mg every morning for 2 weeks and atorvastatin 10 mg every morning
      with cimetidine 300 mg four times a day for 2 weeks, separated by a 4-week
      washout period. Steady-state pharmacokinetic parameters (based on an enzyme
      inhibition assay) and lipid responses were compared. RESULTS: Pharmacokinetic
      parameters and lipid responses were similar following administration of
      atorvastatin alone and atorvastatin with cimetidine. Mean values for Cmax (the
      maximum concentration) were 5.11 ng eq.ml(-1) and 4.54 ng eq.ml(-1), for tmax
      (the time to reach maximum concentration) 2.2 h and 1.3 h, for AUC0-24 (area
      under the concentration-time curve from time 0 h to 24 h) 58.6 ng eq.h.ml(-1) and
      58.5 ng eq.h.ml(-1), and for t1/2 (terminal half-life) 10.1 h and 17.0 h,
      respectively, following administration of atorvastatin alone and atorvastatin
      with cimetidine. Following treatment with atorvastatin alone and atorvastatin
      with cimetidine, mean values for the percentage change from baseline for total
      cholesterol were -29.5% and -29.9%, for low-density lipoprotein (LDL) cholesterol
      -41.0% and -42.6%, for high-density lipoprotein (HDL) cholesterol 6.3% and 5.8%,
      and for triglycerides -33.8% and -25.8%, respectively. CONCLUSIONS: The rate and
      extent of atorvastatin absorption and the effects of atorvastatin on LDL
      cholesterol responses are not influenced by coadministration of cimetidine.

PMID- 9551708
TI  - Effect of the serotonin4 receptor agonist cisapride on plasma aldosterone levels
      in cirrhotic patients with secondary hyperaldosteronism.

PMID- 9551709
TI  - The neuropharmacology of yawning.
AB  - Yawning is a phylogenetically old, stereotyped event that occurs alone or
      associated with stretching and/or penile erection in humans and in animals from
      reptiles to birds and mammals under different conditions. Although its
      physiological function is still unknown, yawning is under the control of several
      neurotransmitters and neuropeptides at the central level as this short overview
      of the literature on the neurochemistry of yawning shows. Among these substances,
      the best known are dopamine, excitatory amino acids, acetylcholine, serotonin,
      nitric oxide, adrenocorticotropic hormone-related peptides and oxytocin, that
      facilitate yawning and opioid peptides that inhibit this behavioral response.
      Some of the above compounds interact in the paraventricular nucleus of the
      hypothalamus to control yawning. This hypothalamic nucleus contains the cell
      bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas that
      play a key role in the expression of this behavioral event. When activated by
      dopamine, excitatory amino acids and oxytocin itself, these neurons facilitate
      yawning by releasing oxytocin at sites distant form the paraventricular nucleus,
      i.e. the hippocampus, the pons and/or the medulla oblongata. Conversely,
      activation of these neurons by dopamine, oxytocin or excitatory amino acids, is
      antagonized by opioid peptides, that, in turn, prevent the yawning response. The
      activation and inhibition, respectively of these oxytocinergic neurons is related
      to a concomitant increase and decrease, respectively, of paraventricular nitric
      oxide synthase activity. However, other neuronal systems in addition to the
      central paraventricular oxytocinergic neurons are involved in the control of
      yawning, since they do not seem to be involved in the expression of yawning
      induced by the stimulation of acetylcholine or serotoninergic receptors, nor by
      adrenocorticotropic hormone (ACTH) and related peptides. Nitric oxide is also
      involved in the induction of yawning by the latter compounds and neuronal links,
      for instance between dopamine and acetylcholine and dopamine and serotonin, seem
      to be involved in the yawning response. Finally, other neurotransmitters, i.e.
      gamma-aminobutyric acid (GABA) and noradrenaline, and neuropeptides, i.e.
      neurotensin and luteinizing hormone-releasing hormone (LH-RH), influence this
      behavioral response. In conclusion, in spite of some recent progress, little is
      known of, and more has to be done to identify, the neurochemical mechanisms
      underlying yawning at the central level.

PMID- 9551710
TI  - Role of corticotropin-releasing factor in forced swimming test.
AB  - Several aspects of the role of corticotropin-releasing factor (CRF) in the forced
      swimming test were investigated in this study by using two different
      administration schedules. I.c.v. microinjection of CRF produced a dose-dependent
      increase in swimming activity when the administration schedule originally
      reported for this test to screen antidepressant drugs was followed. The most
      effective doses were 1 and 3 microg of CRF. A lower dose of CRF (0.5 microg) was
      also effective when repetitive experimental stress was present. CRF receptor
      antagonist, alpha-helical CRF-(9-41) (alpha-helical CRF-(9-41)), was able to
      block CRF-induced increases in swimming in all sessions of the forced swimming
      test. However, the effects of CRF and CRF receptor antagonist depended on the
      administration schedule. A decrease in swimming in the forced swimming test was
      observed when CRF and CRF receptor antagonist were given together, using a
      different administration schedule. I.c.v. CRF was ineffective and CRF receptor
      antagonist alone produced an increase in swimming when administered according to
      this schedule. These behavioural responses were maintained after twelve days
      without any treatment. The results of the current study suggest that endogenous
      CRF seems to play a determinant role in behavioural responses in the forced
      swimming test. The involvement of the level of activation and memory processes in
      these behavioural responses is discussed.

PMID- 9551711
TI  - Involvement of endothelium in relaxant action of glibenclamide on the rat
      mesenteric artery.
AB  - The present report describes the complex effect of glibenclamide, an antidiabetic
      sulfonylurea agent, on the rat isolated mesenteric artery. Although glibenclamide
      concentration dependently reversed the relaxant effect of pinacidil, an activator
      of ATP-sensitive K+ channels (the concentration for half-maximum reversal effect
      was 0.56 microM with endothelium and 0.17 microM without endothelium), in the
      artery precontracted with phenylephrine (1 microM), it relaxed phenylephrine
      induced sustained contraction at higher concentrations (IC50: 4.4+/-1.1 microM
      with endothelium and 226.1+/-44.2 microM without endothelium). The relaxant
      effect of glibenclamide was partially inhibited by pretreatment of the artery
      with either NG-nitro-L-arginine (10-100 microM) or methylene blue (1 microM).
      Indomethacin (10 microM) had no effect. Moreover, glibenclamide also
      concentration dependently (3-500 microM) reduced the sustained contraction
      induced by 60 mM K+ (IC50: 99.5+/-16.1 microM). The relaxation induced by
      glibenclamide was not affected by various putative K+ channel blockers such as
      charybdotoxin (100 nM), tetraethylammonium ions (1 mM), apamin (100 nM) and 4
      aminopyridine (1 mM). The results indicate an involvement of the endothelium,
      probably of nitric oxide, in the relaxation induced by glibenclamide in the
      endothelium-intact rat mesenteric arteries. The inhibitory effect of
      glibenclamide on the high-K+-induced contraction suggests that glibenclamide may
      interfere with Ca2+ influx, which in turn affects intracellular Ca2+ levels in
      arterial smooth muscle, leading to reduction of muscle contractility. It is
      suggested that two distinct pharmacological effects induced by glibenclamide may
      be mediated through different glibenclamide binding sites, however, the data show
      an overlap of concentrations of glibenclamide for producing the two effects in
      rat isolated mesenteric arteries.

PMID- 9551712
TI  - Characterization of oxytocin actions in guinea-pig isolated uterine artery: the
      effect of pregnancy.
AB  - While the contractile effect of oxytocin on uterine artery has been reported,
      little is known about whether pregnancy affects the responsiveness of this artery
      to oxytocin. If it does, is it a consequence of changed endothelial function, as
      has been proposed for some other vasoconstrictors. Furthermore, the receptor
      subtypes involved in oxytocin action on uterine artery has not been yet
      determined. Therefore the purposes of this study were to (1) determine the
      receptor subtypes involved in oxytocin action in non-pregnant and pregnant guinea
      pig uterine artery and to (2) determine whether possible changes in uterine
      artery sensitivity to oxytocin during pregnancy are due to altered endothelial
      function. Therefore, the effect of oxytocin on non-pregnant and pregnant guinea
      pig uterine arterial rings with and without endothelium was investigated. In non
      pregnant guinea-pig uterine artery oxytocin induced contraction (pEC50 = 7.63)
      with greater potency than in pregnant guinea-pig uterine artery (pEC50 = 7.17).
      Removal of the endothelium did not affect oxytocin-induced contractions,
      regardless of the pregnancy status. The uterine arteries did not respond to
      [Thr4, Gly7]oxytocin. In the preparations studied, [d(CH2)5Tyr(Me)2]vasopressin
      and [d(CH2)5, D-Ile2, Ile4]vasopressin antagonized oxytocin action with the
      following pKB values ([d(CH2)5Tyr(Me)2]vasopressin versus [d(CH2)5, D-Ile2,
      Ile4]vasopressin): 8.24 versus 7.29 and 8.11 versus 7.17 for non-pregnant guinea
      pig uterine artery with and without endothelium, respectively; 8.39 versus 7.25
      and 8.35 versus 7.25 for pregnant guinea-pig uterine artery with and without
      endothelium, respectively. We suggest that, in uterine arteries, oxytocin induces
      contraction by activation of vasopressin V1A receptors. The potency of oxytocin
      in uterine artery is decreased during pregnancy and this is not associated with
      altered endothelial function.

PMID- 9551713
TI  - Myosin light chain phosphorylation and Mn2+ -dependent norepinephrine-induced
      contractions in guinea-pig vas deferens.
AB  - We have reported that norepinephrine but not K+ induced a sustained and dose
      dependent contraction without extracellular Ca2+ and Mn2+ in Ca2+-depleted Mn2+
      loaded vas deferens from the guinea-pig. In the present study, we determined the
      phosphorylation of the 20-kDa myosin light chain and examined the effects of
      inhibitors of calmodulin and myosin light chain kinase on the Mn2+-dependent
      norepinephrine-induced contraction in order to evaluate the contribution of
      phosphorylation to this contraction. W-7 [N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide], ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-homopiperazine]
      and wortmannin inhibited this contraction. However, the Mn2+-dependent
      norepinephrine-induced contraction developed without a significant increase in
      the phosphorylation of the 20-kDa myosin light chain. In beta-escin-permeabilized
      preparations, Mn2+ induced contractions that were inhibited by ML-9. These
      results suggest that the activation of myosin light chain kinase is essential for
      the development of Mn2+-dependent norepinephrine-induced contractions and that
      the phosphorylation of myosin light chain may act as a trigger for these
      contractions.

PMID- 9551714
TI  - Studies on curare-like action of the tripeptide carbobenzoxy-Gly-Gly-Arg-beta
      naphthylamide in mouse diaphragm.
AB  - The effects of several protease substrates or protease inhibitors on
      neuromuscular transmission in the isolated mouse phrenic nerve-diaphragm were
      studied. N-Carbobenzoxy-Gly-Gly-Arg-beta-naphthylamide (Z-GGR-N) but none of the
      other agents inhibited the nerve-evoked muscle contractions. By means of
      electrophysiological studies, Z-GGR-N was found to inhibit the amplitudes of both
      end-plate potentials (epps) (IC50 approximately 50 microM) and miniature end
      plate potentials (mepps) but to increase the frequencies of mepps. This
      tripeptide could protect the nicotinic acetylcholine receptor from the
      irreversible inhibitory action of alpha-bungarotoxin on the mouse diaphragm.
      Similar to D-tubocurarine, Z-GGR-N induced tetanic fading both of nerve-evoked
      muscle contractions and of the amplitude of epps. Furthermore, Z-GGR-N exhibited
      a greater depression of the amplitudes of train-epps than those of mepps, similar
      to that of hexamethonium and D-tubocurarine, indicating an effect on presynaptic
      autoreceptors. Suramin, which could competitively reverse the inhibitory effects
      of non-depolarizing relaxants, acted in this study as an antagonist of all the
      effects of Z-GGR-N, especially those at the presynaptic site. All of these
      findings suggest that Z-GGR-N is a novel tripeptide possessing curare-like
      actions at both presynaptic and postsynaptic sites and that these actions are
      independent of its protease substrate property.

PMID- 9551715
TI  - Comparison of in vitro effects of triflusal and acetysalicylic acid on nitric
      oxide synthesis by human neutrophils.
AB  - Recent studies have suggested that the protective anti-ischemic effects of
      acetylsalicylic acid are stronger than the inhibition of platelet thromboxane A2
      synthesis. Since ischemic events still occur in acetylsalicylic acid-treated
      patients, the development of new drugs with more powerful protective effects is
      needed. We compared the effects of a new platelet antiaggregating drug, 2-acetoxy
      4-trifluoromethyl-benzoic acid (triflusal) and of acetylsalicylic acid on the
      interaction between human neutrophils and platelets, examining the capability of
      neutrophils to generate nitric oxide (NO). Triflusal, in the presence of
      neutrophils, showed a greater antiplatelet potency than acetylsalicylic acid to
      inhibit thrombin-induced platelet activation. Significant stimulation of NO
      mediated mechanisms in the presence of acetylsalicylic acid or triflusal was
      demonstrated by the following findings: (1) increased metabolism of arginine to
      citrulline, (2) increase of cGMP in the platelet/neutrophil system and (3) the
      inhibitory action of the L-arginine (L-Arg) competitive analogue, NG-nitro-L
      arginine-methyl ester (L-NAME), which was reversed by L-Arg. Triflusal increased
      the stimulation of NO synthesis by neutrophils more than did of acetylsalicylic
      acid. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethylbenzoic acid
      (HTB), alone or in combination with acetylsalicylic acid, did not modify NO
      production by neutrophils. Therefore, the whole molecule of triflusal is needed
      to stimulate NO production by neutrophils. Our results show that, in the presence
      of neutrophils, triflusal exerts an antiplatelet effect greater than that of
      acetylsalicylic acid, demonstrating a more powerful stimulation of the NO/cGMP
      system. The present results indicate that it is possible to develop new and more
      potent acetylsalicylic acid-related antiplatelet drugs for the prevention of the
      myocardial ischemic/reperfusion processes.

PMID- 9551717
TI  - Magnolol inhibits Mac-1 (CD11b/CD18)-dependent neutrophil adhesion: relationship
      with its antioxidant effect.
AB  - Magnolol, a phenolic compound isolated from a Chinese herbal drug, Magnolia
      officinalis, has been shown to protect rat heart from ischemia/reperfusion
      injury. Neutrophil adhesion plays a crucial process during this inflammatory
      response. To evaluate whether magnolol prevents ischemia/reperfusion injury by
      inhibiting neutrophil adhesion, we determined whether magnolol can inhibit
      adhesion of phorbol-12-myristate-13-acetate (PMA)-activated human neutrophils to
      a fibrinogen-coated surface in a dose-dependent manner. Using flow cytometric
      analysis, we observed that magnolol pretreatment (10 min at 37 degrees C)
      diminished PMA (100 ng/ml)-induced Mac-1 upregulation. PMA also induced rapid
      intracellular accumulation of superoxide (O2-.) and hydrogen peroxide (H2O2) in
      neutrophils; magnolol pretreatment attenuated the accumulation of these two
      substances. Inhibition of reactive oxygen species by superoxide dismutase and/or
      catalase, which decompose O2-. and H2O2, respectively, also abolished Mac-1
      upregulation and neutrophil adhesion. We conclude that magnolol inhibits
      neutrophil adhesion and that this can account for its anti-ischemia/reperfusion
      injury effect. We propose that the inhibitory effect of magnolol on neutrophil
      adhesion to the extracellular matrix is mediated, at least in part, by inhibition
      of the accumulation of reactive oxygen species, which in turn suppresses the
      upregulation of Mac-1 that is essential for neutrophil adhesion.

PMID- 9551716
TI  - Characterization of binding sites of a new neurotensin receptor antagonist,
      [3H]SR 142948A, in the rat brain.
AB  - The present study describes the characterization of the binding properties and
      autoradiographic distribution of a new nonpeptide antagonist of neurotensin
      receptors, [3H]SR 142948A (2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3
      dimethylaminopropyl)-N-methyl carbamoyl)-2-isopropylphenyl)-1H-pyrazole-3
      carbonyl]-amino]-ad amantane-2-carboxylic acid, hydrochloride), in the rat brain.
      The binding of [3H]SR 142948A in brain membrane homogenates was specific, time
      dependent, reversible and saturable. [3H]SR 142948A bound to an apparently
      homogeneous population of sites, with a Kd of 3.5 nM and a Bmax value of 508
      fmol/mg of protein, which was 80% higher than that observed in saturation
      experiments with [3H]neurotensin. [3H]SR 142948A binding was inhibited by SR
      142948A, the related nonpeptide receptor antagonist, SR 48692 (2-[[1-(7
      chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole -3-carbonyl]amino]
      adamantane-2-carboxylic acid) and neurotensin. Saturation and competition studies
      in the presence or absence of the histamine H1 receptor antagonist,
      levocabastine, revealed that [3H]SR 142948A bound with similar affinities to both
      the levocabastine-insensitive neurotensin NT1 receptors (20% of the total binding
      population) and the recently cloned levocabastine-sensitive neurotensin NT2
      receptors (80% of the receptors) (Kd = 6.8 and 4.8 nM, respectively). The
      regional distribution of [3H]SR 142948A binding in the rat brain closely matched
      the distribution of [125I]neurotensin binding. In conclusion, these findings
      indicate that [3H]SR 142948A is a new potent antagonist radioligand which
      recognizes with high affinity both neurotensin NT1 and NT2 receptors and
      represents thus an excellent tool to study neurotensin receptors in the rat
      brain.

PMID- 9551718
TI  - Necessity of interleukin-1beta converting enzyme cascade in taxotere-initiated
      death signaling.
AB  - Taxotere is a new type chemotherapeutic agent which targets tubulin. In the
      present study, we investigated the molecular machinery of taxotere-initiated
      death signaling. Taxotere induced cell death in mouse fibroblast L929 cells. Cell
      morphological analysis revealed that this effect showed characteristics of
      apoptotic and necrotic cell death. To further examine taxotere-induced cell
      death, we investigated the direct involvement of caspase. When cells were
      pretreated with the synthesized tetrapeptide inhibitor of caspase, YVAD-CHO (Ac
      Tyr-Val-Ala-Asp-aldehyde: inhibitor of interleukin-1beta converting enzyme (ICE)
      subfamily) or DEVD-CHO (Ac-Asp-Glu-Val-Asp-aldehyde: inhibitor of CPP32
      subfamily), taxotere-induced cell death was prevented. In addition, time course
      experiments demonstrated that activation of the ICE subfamily preceded activation
      of the CPP32 subfamily in taxotere-initiated death signaling, suggesting the
      direct involvement of the ICE cascade in taxotere-initiated death signaling. On
      the basis of these results, we suggest that taxotere causes the initiation of ICE
      cascade in its death signaling pathway and that the down-stream site of taxotere
      initiated death signaling is the same as that of other chemotherapeutic agents.

PMID- 9551719
TI  - [3H]RS79948-197 binding to human, rat, guinea pig and pig alpha2A-, alpha2B- and
      alpha2C-adrenoceptors. Comparison with MK912, RX821002, rauwolscine and
      yohimbine.
AB  - The Kd values of the recently introduced radioligand [3H]RS79948-197 ((8a
      R,12aS,13a-S)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-metho xy-12
      (ethylsulphonyl)-6H-isoquino[2,1-g][1,6]naphthyridine) were determined for the
      recombinant human and rat alpha2A-, alpha2B- and alpha2C- as well as guinea pig
      alpha2B- and alpha2c-adrenoceptors expressed in COS (CV-1 Origin, SV40) cells. In
      addition, the Kd values were also determined for [3H]RS79948-197 for the guinea
      pig spleen alpha2A-adrenoceptor and for pig alpha2A-, alpha2B- and alpha2C
      adrenoceptors in membranes obtained from kidney and striatum. Available
      radioligands for alpha2-adrenoceptors, besides [3H]RS79948-197 are the tritiated
      forms of MK912 ((2S,12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octa hydro-2H
      benzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2'-one), RX821002 (2-methoxy
      idazoxan), rauwolscine and yohimbine. In the present article the binding
      constants of all these substances for the alpha2A-, alpha2B- and alpha2C
      adrenoceptor subtypes in human, pig, rat and guinea pig are reviewed. In all
      species tested MK912 was alpha2C-selective, RX821002 showed a minor alpha2A
      selectivity, whereas [3H]RS79948-197 was non-selective among the alpha2
      adrenoceptor subtypes, showing high affinity for all three subtypes. Rauwolscine
      and yohimbine showed relatively low affinities for nmost of the alpha2
      adrenoceptor subtypes investigated, the exception being rauwolscine having high
      affinity for the human and porcine alpha2C-adrenoceptors.

PMID- 9551720
TI  - Atypical effect of dopamine in modulating the functional inhibition of NMDA
      receptors of cultured retina cells.
AB  - Cultured retina cells released accumulated [3H]GABA (gamma-aminobutyric acid)
      when stimulated by L-glutamate, N-methyl-D-aspartate (NMDA) and kainate. In the
      absence of Mg2+, dopamine at 200 microM (IC50 60 microM), inhibited in more than
      50% the release of [3H]GABA induced by L-glutamate and NMDA, but not by kainate.
      This effect was not blocked by the D1-like dopamine receptor antagonist, R-(+)-7
      chloro-8-hydroxy-3-methyl- -phenyl-2,3,4,5-tetrahydro- H-3-benzazepine
      hydrochloride (SCH 23390), neither by haloperidol nor spiroperidol (dopamine D2
      like receptor antagonists). The dopamine D1-like receptor agonist R(+)-1-phenyl
      2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,diol hydrochloride (SKF 38393) at 50
      microM, but not its enantiomer, also inhibited the release of [3H]GABA induced by
      NMDA, but not by kainate; an effect that was not prevented by the antagonists
      mentioned above. (+/-)-6-Chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzazepin e hydrobromide (SKF 812497) had no effect. Neither 8BrcAMP (5 mM) nor
      forskolin (10 microM) inhibited the release of [3H]GABA. Our results suggest that
      dopamine and (+)-SKF 38393 inhibit the glutamate and NMDA-evoked [3H]GABA release
      through mechanisms that seem not to involve known dopaminergic receptor systems.

PMID- 9551721
TI  - A novel cause for bronchiolitis obliterans organizing pneumonia: exposure to
      paint aerosols in textile workshops.

PMID- 9551722
TI  - Reduced smoking--an acceptable goal for the hopeless heavy smoker?

PMID- 9551723
TI  - Organizing pneumonia in textile printing workers: a clinical description.
AB  - In April 1992 an outbreak of severe respiratory illness occurred among
      aerographic textile workers in the area of Alcoi, Autonomous Community of
      Valencia, Spain. An epidemiological study linked this outbreak to the use of a
      reformulated aerosolized product, Acramin-FWN. We analyzed clinical, laboratory,
      and pathological data of the first 14 patients with confirmed organizing
      pneumonia (OP) secondary to this newly recognized occupational toxicant. The mean
      age of the patients was 30 yrs. The most common clinical findings were cough
      (86%), epistaxis (71%), dyspnoea (64%), oppressive chest pain (57%), and crackles
      (50%). A restrictive functional pattern was evident in 64%. Radiographic findings
      consisted predominantly of patchy infiltrates in 65% and a micronodular pattern
      in 35%. Treatment with corticosteroids did not prevent initial progression in 11
      of the 14 patients and development of irreversible respiratory failure in five
      patients. At necropsy, besides features of OP, interstitial fibrosis and diffuse
      alveolar damage were evident. A low total lung capacity, the presence of crackles
      at admission, and increases in the alveolar-arterial oxygen difference were
      predictive of death. The organizing pneumonia caused by the inhalation of Acramin
      FWN is characterized by a tendency to evolve into progressive interstitial
      fibrosis despite the use of corticosteroids. The illness is restricted to the
      respiratory system and once respiratory failure has developed the prognosis is
      poor.

PMID- 9551724
TI  - Bronchial responsiveness in active steelworkers.
AB  - Coke-oven workers are exposed to dust and irritant gases. Therefore they are at
      risk of developing lung diseases including chronic bronchitis. Nonspecific
      bronchial hyperresponsiveness (BHR) has been advocated as a potential risk factor
      predisposing to the development of chronic bronchitis. In a previous study, we
      showed that prevalence of BHR was higher in retired coke-oven workers than in
      retired blast furnace workers. The present study was carried out to determine the
      prevalence of BHR in active steelworkers. Thus, 137 coke-oven workers and 150
      blast furnace workers underwent clinical examination, a standardized
      questionnaire for the study of respiratory symptoms, pulmonary function testing
      and methacholine aerosol challenge. The study demonstrates a higher prevalence
      and degree of BHR [provocative concentration of methacholine causing a 20% fall
      in forced expiratory volume in one second (PC20) < or = 8 mg x mL(-1)] in coke
      oven workers than in blast furnace workers (31.4 versus 6.7%; p<0.001). Moreover,
      the frequency of respiratory symptoms and basal bronchial obstruction were
      greater among coke-oven workers with BHR in nonresponders. The basal maximum
      expiratory flow from 25-75% of forced vital capacity and the respiratory symptoms
      were correlated with bronchial responsiveness. The lack of correlation observed
      between BHR and the intensity of smoking or years spent in coke-oven environment
      may be explained by the high proportion of smokers, the worker turnover in the
      steel plant, and the "healthy worker effect". In conclusion, the higher
      prevalence and degree of bronchial hyperresponsiveness in coke-oven workers
      suggests that coke-oven pollutants are more intense irritants than those that
      escape from blast furnaces.

PMID- 9551725
TI  - The Po River Delta Respiratory Epidemiological Survey: an analysis of factors
      related to level of total serum IgE.
AB  - The purpose of the present study was to analyse whether sex, age, skin test
      reactivity, cigarette smoking and occupational exposure were related to the total
      serum immunoglobulin (Ig)E concentrations (kU x L[-1]), in a general population
      sample. We studied 1,905 subjects (915 males, 990 females) of a general
      population sample (n=2,841, 8-73 yrs) participating in the second cross-sectional
      respiratory epidemiological survey in the rural Po Delta area (near Venice, North
      Italy). Distribution of total serum IgE concentrations was skewed, thus a log
      transformation was performed to obtain a Gaussian shape. Significantly higher
      values of IgE were found in males compared to females. In general, a peak of IgE
      concentration was found at 8-14 yrs. IgE values tended to be lower in older than
      younger adults. Significantly higher serum IgE levels were shown in subjects with
      a positive skin-prick test index (ST+) than in those with a negative skin-prick
      test index (ST-). There was a significant relationship of total IgE levels with
      skin reactivity to pollens and house-dust mites. In both sexes higher values of
      IgE were found in current smokers than in ex-nonsmokers, regardless of skin-test
      reactivity. There was no significant difference in IgE values between ex- and
      nonsmokers. Passive smoking and occupational exposure were significantly related
      to increased IgE values. Our results confirm that in a general population sample
      immunoglobulin E concentrations are related not only to skin-prick test
      reactivity to common aeroallergens, but also to other risk factors for chronic
      obstructive lung diseases, such as sex, active/ passive smoking and occupational
      exposure.

PMID- 9551726
TI  - Effectiveness of postal smoking cessation advice: a randomized controlled trial
      in young men with reduced FEV1 and asbestos exposure.
AB  - There have been few community-based randomized, controlled intervention trials
      for cessation in high-risk smokers. In such a trial we evaluated the effects of
      postal smoking cessation advice in smokers with asbestos exposure and/or reduced
      forced expiratory volume in one second (FEV1). All men aged 30-45 yrs (n=22,392)
      living in 34 municipalities in western Norway were invited to a cross-sectional
      community survey. Information on smoking habits and occupational asbestos
      exposure were obtained from self-administered questionnaires and measurements of
      FEV1 were performed with dry-wedge bellow spirometers. Among 16,393 participants
      we identified a group of 2,610 smokers with previous occupational asbestos
      exposure and/or adjusted FEV1 in the lowest quartile. A random half (n=1,300)
      received a mailed personal letter from a respiratory physician with a person
      specific health advice to quit smoking and a pamphlet on smoking cessation. The
      remaining smokers (n=1,310) acted as controls and did not receive any
      information. Twelve months after the intervention, information on smoking habits
      was re-examined using a postal questionnaire. Among the respondents (n=2,282),
      smoking cessation was reported altogether by 13.7% in the intervention group
      versus 9.9% in the control group (p<0.01). The 1 yr sustained quit rate (no
      smoking at all during the last year) was 5.6 versus 35% (p<0.05), respectively.
      Measurements of carbon monoxide in expired air (with < or = 10 parts per million)
      confirmed self-reported nonsmoking in samples of the two groups. In a community
      this simple postal smoking cessation advice from a respiratory physician based on
      person-specific risk factors improved the 1 yr sustained success rate by 60% in
      identified high-risk smokers.

PMID- 9551728
TI  - Interleukin-8 plays a significant role in IgE-mediated lung inflammation.
AB  - Interleukin (IL)-8 is a potentially important cytokine in allergic respiratory
      responses since it is released by many resident lung cells, and it is a potent
      granulocyte chemoattractant. Therefore, we induced an immunoglobulin (Ig)E
      mediated response in human lung samples and studied whether IL-8 was produced in
      sufficient quantities to promote human neutrophil and eosinophil migration across
      naked filters and endothelial and pulmonary epithelial monolayers cultured on
      these filters. Fresh human lung fragments from 16 thoracotomy specimens were
      treated with either a 1:100 dilution of anti-IgE or buffer (control) for 30 min.
      All anti-IgE treated lung samples had significant release of histamine and
      neutrophil and eosinophil chemotactic activity. Fourteen of the 16 lung samples
      had a significant increase in IL-8 subsequent to anti-IgE treatment (p<0.01).
      Anti-IL-8 antibody (4 microg x mL[-1]) inhibited 42% and 53% of neutrophil and
      eosinophil chemotactic activity respectively, contained in supernatants from anti
      IgE-treated lung samples. Finally, we found that IL-8 at a concentration near
      that measured after anti-IgE treatment of lung samples (2,000 pg x mL[-1])
      induced neutrophil and eosinophil migration through naked filters and endothelial
      and pulmonary epithelial cell monolayers. Thus, human lung IgE-mediated responses
      in vitro results in the rapid release of interleukin-8 in amounts sufficient to
      affect a biological response, granulocyte transcellular migration, indicating
      that interleukin-8 may play a significant role in allergic respiratory diseases.

PMID- 9551727
TI  - Murine strain differences in airway inflammation caused by diesel exhaust
      particles.
AB  - To elucidate whether immunoglobulin (Ig) E or IgG are involved in the murine
      asthma model, we compared the pathogenic features of mice that were high IgG
      responders (C3H/He) with mice that were high IgE responders (BALB/c) after
      intratracheal instillation of diesel exhaust particles (DEP) and ovalbumin
      sensitization. Both mouse strains received DEP intratracheally once a week for 5
      weeks. After the second injection of DEP, ovalbumin and aluminium hydroxide were
      injected intraperitoneally. After the last DEP administration, the mice were
      challenged by exposure to an aerosol of ovalbumin. DEP caused increased IgG1
      production and airway hyperresponsiveness after ovalbumin sensitization in C3H/He
      mice, although IgE production did not change in either strain. Furthermore, in
      C3H/He mice, the number of eosinophils and goblet cells in the bronchial
      epithelium, and the expression of interleukin-5 and interleukin-2 were increased
      by DEP and ovalbumin treatments. In contrast, the pathogenic changes in BALB/c
      mice were weak, even though the same protocol was used. In conclusion, murine
      strain differences in response to air pollutants and allergens seem to be related
      to antigen-specific immunoglobulin G1 production and cytokine expression in the
      lungs.

PMID- 9551729
TI  - Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8.
AB  - Repeated intranasal administration of interleukin 8 (IL-8) induces bronchial
      hyperresponsiveness (BHR) accompanied by lower airway neutrophil accumulation
      (ANA) in guinea-pigs. Leukotriene B4 (LTB4) is a chemotactic factor for
      neutrophils. To elucidate whether LTB4 and neutrophil elastase are involved in
      the IL-8-induced BHR and ANA, the effects of a LTB4 antagonist (ONO-4057) and a
      neutrophil elastase inhibitor (ONO-5046) on the responses were examined. IL-8 (5
      microg x kg[-1]) was administered intranasally to guinea-pigs twice weekly for 3
      weeks. One day after the last administration, animals were anaesthetized and
      artificially ventilated through tracheal cannulae, and lateral pressure at the
      tracheal cannula (Pao) was measured as an overall index of airway responses to
      inhaled histamine. ONO-4057 (2 or 20 mg x kg[-1]) or ONO-5046 (30 or 300 mg x kg[
      1]) was administered intraperitoneally 24 and 1 h before anaesthesia. ONO-4057,
      but not ONO-5046, significantly inhibited the IL8-induced BHR and ANA, assessed
      by bronchoalveolar lavage, in a dose-dependent manner. These findings suggest
      that interleukin 8 causes bronchial hyperresponsiveness and airway neutrophil
      accumulation in guinea-pigs in vivo. In part this appears to be due to release of
      leukotriene B4, whereas it may not be mediated by neutrophil elastase.

PMID- 9551730
TI  - Elevated serum interferon-gamma in atopic asthma correlates with increased
      airways responsiveness and circadian peak expiratory flow variation.
AB  - Interleukin (IL)-4, IL-5 and interferon (IFN)-gamma are thought to play an
      important role in chronic airway inflammation in asthmatic subjects. Increased
      airways responsiveness and nocturnal airway obstruction are important clinical
      manifestations of asthma. The aim of this study was to investigate whether IL-4,
      IL-5 and IFN-gamma values are elevated in atopic asthma and correlate with its
      clinical manifestations. Serum IL-4, IL-5 and IFN-gamma levels of 17 atopic
      asthmatics and eight nonatopic healthy subjects were determined at 16:00 and
      04:00 h by a chemiluminescence enzyme-linked immunosorbent assay (ELISA) method.
      The clinical manifestation of asthma was determined by assessment of the degree
      of airway obstruction, airways responsiveness to methacholine and severity of
      nocturnal airway obstruction, defined as the mean circadian (16:00-04:00 h) peak
      expiratory flow (PEF) variation. Serum IL-4, IL-5 and IFN-gamma levels were
      significantly higher in asthmatic subjects as compared to healthy controls, both
      at 16:00 and 04:00 h. In asthmatic subjects serum IFN-gamma at both time points
      correlated significantly with the provocative concentration of methacholine
      causing a 20% fall in forced expiratory volume in one second (PC20,meth) (rho= -
      0.55) and with the mean 16:00-04:00 h PEF variation (rho = 0.53). In contrast, no
      relationship was found between the levels of IL-4 and IL-5 and the parameters of
      clinical manifestation of asthma. The results suggest that the serum interferon
      gamma level is a reflection of the severity of airway inflammation in atopic
      asthma. More studies are needed to detect the cellular sources and to clarify the
      exact roles of interferon-gamma and other pro-inflammatory cytokines in asthma.

PMID- 9551731
TI  - CD14 expression and soluble CD14 after segmental allergen provocation in atopic
      asthma.
AB  - Allergic asthma is associated with the recruitment of activated inflammatory
      cells after allergen challenge. Surface expression of CD14 has been proposed as a
      marker of cell activation and differentiation. We therefore measured CD14
      expression on activated macrophages and granulocytes as well as soluble CD14
      (sCD14) concentrations in peripheral blood and bronchoalveolar lavage (BAL)
      following segmental allergen provocation (SAP) with individually standardized
      doses of allergen in eight patients with allergic asthma. Two segments of the
      right lung were challenged with allergen. Two segments of the left lung, into
      which saline was instilled, served as controls. CD14 expression on macrophages
      and granulocytes was determined by flow-cytometry and concentrations of
      interleukins and sCD14 were analysed by enzyme-linked immunosorbent assay (ELISA)
      10 min and 18 h after challenge. Soluble CD14 concentrations remained unchanged
      in BAL fluid after saline challenge and 10 min after SAP, but increased
      significantly 18 h after SAP. Although macrophage numbers increased 18h after
      SAP, CD14 expression on these cells did not change. Unlike macrophages,
      granulocyte numbers correlated with sCD14 levels 18 h after SAP while their CD14
      expression decreased significantly. Furthermore, sCD14 correlated with
      interleukin (IL)-13 concentrations 18 h after SAP. An increase in soluble CD14
      can be observed 18 h but not 10 min after segmental allergen provocation
      suggesting local release of this surface antigen. Our findings imply that CD14
      mediated cell activation following segmental allergen provocation could play a
      role in asthmatic inflammation.

PMID- 9551732
TI  - Attenuation of virus-induced airway dysfunction in rats treated with imiquimod.
AB  - Viral respiratory infections cause acute airway abnormalities consisting of
      inflammation and physiological dysfunction in both animals and humans. It is
      likely that inflammatory cell products, such as cytokines, contribute
      substantially to viral-induced airway dysfunction. We hypothesized that
      imiquimod, an immune response enhancing agent that induces interferon-alpha,
      would attenuate the development of airway dysfunction during acute viral illness
      in rats. Adult Brown Norway rats were inoculated with parainfluenza type 1
      (Sendai) virus or sterile vehicle, and treated with either imiquimod or water.
      Respiratory system resistance (Rrs), arterial oxygen tension (Pa,O2), lung viral
      titres and bronchoalveolar lavage (BAL) leucocyte counts were measured in
      anaesthetized, paralysed, ventilated rats. Virus-infected, water-treated rats had
      a significant decrease in Pa,O2 and had significant increases in leucocyte count
      and Rrs when compared to both the virus-infected, imiquimod-treated, (Pa,O2, p =
      0.03; leucocyte count, p = 0.02; and Rrs, p = 0.009) and noninfected, water
      treated rats (Pa,O2, p = 0.007; leucocyte count, p = 0.001; and Rrs, p = 0.01).
      In addition, imiquimod suppressed BAL eosinophils in both virus-infected (p =
      0.02) and noninfected (p = 0.001) groups, and lowered overall virus titres (p =
      0.03). Thus, both virus-induced airway inflammation and physiological dysfunction
      were attenuated significantly by imiquimod treatment in this animal model. By
      further delineating mechanisms by which infections induce airway dysfunction in
      animal models, more specific pharmacological interventions can be developed for
      the treatment of virus-induced asthma.

PMID- 9551733
TI  - Influence of external pH on ciliary beat frequency in human bronchi and
      bronchioles.
AB  - Ciliated respiratory epithelial cells have to tolerate variations in local pH
      caused by the respiratory cycle and potential ventilation-perfusion mismatches.
      We showed previously that peripheral bronchiolar cilia beat at a lower frequency
      than bronchial cilia, and have now investigated whether they show differences in
      tolerance to changes in pH. Using the image analysis system applied in the
      previous study, we compared variations in the ciliary beat frequencies (CBF) of
      bronchi and bronchioles sampled from human lung resections at various pH in
      vitro. Application of nonparametric tests (the variance of samples was not
      similar) indicated that CBF was not significantly modified when pH was varied
      between 7.5 and 10.5 for bronchi, and between 5.5 and 10.5 for bronchioles.
      Reversible and significantly lower CBF were observed below pH 7.0 for bronchi and
      below pH 5.0 for bronchioles. Extreme pH values such as 11.0 or 3.0 were lethal
      within a few minutes. Thus, respiratory ciliary beating is able to tolerate
      external pH variations between 3.5 and 10.5 without permanent impairment. In
      addition we found that alkaline pH values are more favourable than acidic ones
      and that bronchiolar ciliated cells are more tolerant to acidic pH than bronchial
      cells.

PMID- 9551734
TI  - Bronchial temperature reflects transcapillary heat transport of isolated blood
      perfused rabbit lungs.
AB  - The pulmonary capillaries are in such close proximity to the terminal airways
      that changes in capillary blood temperature should also cause changes in
      bronchial wall temperature. Therefore, we hypothesized that injection of cold
      solutions into the pulmonary artery would yield bronchial temperature-time curves
      similar to those in the pulmonary artery and left atrium. These bronchial curves
      should mainly represent the capillary bed. Isolated rabbit lungs (n=8) were
      ventilated (5% CO2 in air) and perfused (autologous blood, 37 degrees C) at
      various flow rates (50-200 mL x min[-1]). Thermistor probes (diameter 0.46 mm)
      registered temperature changes in the pulmonary artery, at the bronchial wall
      (wedge position) and in the left atrium after injection of 0.8 mL Ringer's
      lactate (0 degrees C) into the pulmonary artery. Bronchial temperature-time
      curves were found to resemble "dilution" curves located between pulmonary
      arterial and left atrial curves. Independent of flow rate, their appearance
      times, peaks and calculated mean transit times were between those from the
      pulmonary artery and the left atrium. We conclude that bronchial temperature-time
      curves reflect transcapillary heat transport and that this approach might be
      useful in gaining further information about vascular transport processes in the
      interior of the lung.

PMID- 9551735
TI  - Action of moguisteine on the activity of tracheobronchial rapidly adapting
      receptors in the dog.
AB  - We have studied the effects of moguisteine, a new non-narcotic, peripherally
      acting antitussive compound, on tracheobronchial rapidly adapting irritant
      receptors (RARs). Experiments were carried out on dogs anaesthetized with a
      mixture of urethane and alpha-chloralose, paralysed with gallamine, vagotomized
      and artificially ventilated. Single unit action potentials identified as
      originating from tracheobronchial RARs were recorded from the peripheral cut end
      of the right vagus nerve. The activity of these receptors was recorded together
      with oesophageal pressure and arterial blood pressure. Fourteen RARs were
      challenged with moguisteine (200 microg x kg[-1] i.v.) in 0.4% dimethylsulphoxide
      (DMSO) or 0.4% DMSO alone (vehicle). Receptor activity was recorded before
      (control) and at 2, 5, 10, 15, 20, 30 and 45 min after administration of the
      challenging compounds. When the results at intervals of 2, 5, 10, 15 and 20 min
      were averaged for each dog, it was found that moguisteine decreased the mean
      activity of the 14 receptors to 75% of the control value (p<0.05); the greatest
      inhibition occurred 10-20 min after moguisteine administration. DMSO did not
      significantly affect the activity of these endings. Oesophageal pressure,
      arterial blood pressure and cardiac frequency were not altered during the
      experimental procedures. The overall results indicate the presence of an
      inhibitory effect of moguisteine on rapidly adapting irritant receptors that
      could account for the antitussigenic effect of this compound.

PMID- 9551736
TI  - Chronic Chlamydia pneumoniae infection and asthma exacerbations in children.
AB  - This study was undertaken to investigate the reported association between
      Chlamydia pneumoniae and Mycoplasma pneumoniae infection and the expression of
      asthma-related symptoms. One hundred and eight children with asthma symptoms,
      aged 9-11 yrs, completed a 13 month longitudinal study. The children maintained a
      daily diary of respiratory symptoms and peak flow rates. When respiratory
      symptoms were reported an investigator was called and a nasal aspirate obtained.
      In total 292 episodes were reported. After the study 65 children provided samples
      when asymptomatic. The presence of infection was investigated by the polymerase
      chain reaction for C. pneumoniae and M. pneumoniae and C. pneumoniae secretory
      immunoglobulin A (IgA) was detected by amplified enzyme immunoassay. C.
      pneumoniae detections were similar between the symptomatic and asymptomatic
      episodes (23 versus 28%, respectively). Children who reported multiple episodes
      also tended to remain PCR positive for C. pneumoniae suggesting chronic infection
      (p< 0.02). C. pneumoniae-specific secretory-IgA antibodies were more than seven
      times greater in subjects who reported four or more exacerbations in the study
      compared to those who reported just one (p<0.02). M. pneumoniae was found in two
      of 292 reports and in two of 65 asymptomatic samples. In conclusion, chronic
      Chlamydia pneumoniae infection is common in schoolage children and immune
      responses to C. pneumoniae are positively associated with frequency of asthma
      exacerbations. We suggest that the immune response to chronic C. pneumoniae
      infection may interact with allergic inflammation to increase asthma symptoms. In
      contrast Mycoplasma pneumoniae was not found to be important in this study.

PMID- 9551737
TI  - Clinical effect of Diskus dry-powder inhaler at low and high inspiratory flow
      rates in asthmatic children.
AB  - In vitro studies with the Diskus inhaler at low and high flow rates show
      consistent doses of drug as fine particles <4.7 microm. The present study was
      designed to ascertain whether this in vitro flow independency translates into
      flow-independent clinical effect when the device is used by patients at low (30 L
      x min[-1]) and high (90 L x min[-1]) flow rates. A pilot study in 129 children
      aged 3-10 yrs demonstrated that 99% of children of 3 yrs and above can generate a
      flow > or = 30 L x min(-1) through the device, while 26% performed > or = 90 L x
      min(-1). Eighteen children aged 8-15 yrs with exercise induced asthma inhaled
      placebo or salmeterol 50 microg at either 30 L x min(-1) or 90 L x min(-1).
      Exercise challenges were carried out 1 h and 12 h after dosing. The maximum
      percentage fall in forced expiratory volume in one second (FEVI) after exercise
      12 h after treatment was significantly less after salmeterol at either flow rates
      as compared to placebo. There was no significant difference in the protection
      from salmeterol on the day of low-flow inhalation versus the day of high-flow
      inhalation. Consistent in vitro fine particle dosing from the Diskus inhaler
      translates into a consistent clinical effect at low and high flow rates in
      children.

PMID- 9551738
TI  - Prevalence of bronchial hyperresponsiveness to 4.5% saline and its relation to
      asthma and allergy symptoms in Austrian children.
AB  - The prevalence of asthma in school children has been reported to have increased,
      with wide variations between countries. To allow comparison of prevalence data,
      objective markers of asthma should be measured. Therefore, we assessed the
      prevalence of bronchial hyperresponsiveness (BHR) to hypertonic saline and its
      relation to asthma and allergy symptoms in 507 Austrian school children, aged 12
      15 yrs in a cross-sectional, community based survey. These children were selected
      from 3,371 children who had answered a self-administered written questionnaire on
      asthma, hay fever, eczema and environmental factors. The prevalence of BHR to
      hypertonic saline was 14% and the majority (70%) of the children had mild BHR.
      The prevalence of wheeze in the last 12 months was 12% and of a diagnostic label
      of asthma was 6%. Fifty three per cent of the children with symptoms in the last
      12 months and a diagnostic label of asthma had BHR, and 33% of those with
      symptoms in the last 12 months regardless of a diagnostic label of asthma showed
      a positive response to hypertonic saline. Atopic dermatitis, a diagnostic label
      of asthma, night cough apart from colds, wheeze in the past 12 months (but not
      "former wheeze") and male gender were significantly associated with increased
      response to 4.5% saline in the final logistic regression model. These results
      show that the prevalence of asthma symptoms in the last 12 months and the
      prevalence of bronchial hyperresponsiveness to hypertonic saline are twice that
      of a diagnosis of asthma and that asthma might be underdiagnosed in the present
      population. The response to hypertonic saline is most strongly associated with
      current asthma and allergy symptoms. A combination of a "diagnostic label of
      asthma" and "asthma symptoms in the last 12 months" might best reflect "current
      asthma" in epidemiological studies in this population.

PMID- 9551739
TI  - Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma
      in children.
AB  - We assessed the clinical and biochemical effects in asthmatic children of fish
      oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty
      acids. Thirty nine asthmatic children aged 8-12 yrs participated in a double
      blind, randomized, controlled trial for 6 months during which they received fish
      oil capsules plus canola oil and margarine (omega-3 group) or safflower oil
      capsules plus sunflower oil and margarine (omega-6 group). Plasma fatty acids,
      stimulated tumour necrosis factor alpha (TNFalpha) production, circulating
      eosinophil numbers and lung function were measured at baseline and after 3 and 6
      months of dietary modification. Day and night symptoms, peak flow rates and
      medication use were recorded for 1 week prior to laboratory visits. Plasma
      phospholipid omega-3 fatty acids were significantly greater in the omega-3 group
      at 3 and 6 months compared to the omega-6 group (p<0.001). In the omega-3 group
      TNFalpha production fell significantly compared with baseline (p=0.026), but the
      magnitude of change between groups did not reach significance (p=0.075). There
      were no significant changes in clinical outcome measures. Dietary enrichment of
      omega-3 fatty acids over 6 months increased plasma levels of these fatty acids,
      reduced stimulated tumour necrosis factor alpha production, but had no effect on
      the clinical severity of asthma in these children.

PMID- 9551740
TI  - Hospitalization for lower respiratory disease during 20 yrs among under 5 yr old
      children in Stockholm County: a population based survey.
AB  - Lower respiratory disease (LRD) is a common cause of hospitalization in infants,
      and episodes of obstructive LRD increase the risk for asthma later in life. The
      purpose of this study was to assess time trends and geographical variation of
      first time hospitalization for LRD among children in Stockholm County, Sweden.
      Data on first time admittance for LRD among children aged up to 5 yrs from 1973
      through 1992 were obtained from the Stockholm County Council hospital discharge
      register, and population register data were used for estimation of the population
      at risk. Municipal data were available for 1982-1992 on outbreaks of respiratory
      syncytial virus (RSV) infections and socio-economic factors. A total of 12,450
      children had been hospitalized for the first time with LRD. For children aged <2
      yrs a 100% increase in the rate of first time hospitalization for LRD was
      observed during the study period and children aged up to 1 yr predominated (50%).
      The average yearly increase in the population based first time hospital admission
      rate for LRD was 1.82%. Males constituted 65% of the cases. Of the diagnoses,
      89.6% were consistent with obstructive LRD, e.g. asthma and obstructive
      bronchitis. In children aged up to 1 yr, peaks in the rate of hospitalization
      tended to coincide with outbreaks of RSV infections. Differences in
      hospitalization between municipalities seemed to be partly explained by
      differences in the admission practices of the four paediatric hospitals in the
      area. We conclude that the increased rate of hospitalization for lower
      respiratory disease in infants of Stockholm County may reflect a true increase in
      the incidence of obstructive respiratory disease. However, several factors
      determine admittance to hospital and the results need to be interpreted with
      caution.

PMID- 9551741
TI  - Inhaled nitric oxide in hypoxaemic newborns who are candidates for extracorporeal
      life support.
AB  - The aim of this study was to evaluate the effect of inhaled nitric oxide (NO) in
      newborns with acute hypoxaemic respiratory failure and the impact of this NO
      therapy on survival and the need for extracorporeal membrane oxygenation (ECMO).
      A cohort of newborns with a gestational age of > or = 34 weeks and an oxygenation
      index (OI) > 25 were prospectively evaluated. Patients were given NO at an
      initial dose of 10 parts per million (ppm). Oxygenation parameters were evaluated
      prior and during NO inhalation. From January 1994 to December 1996, 20 infants
      were enrolled in the study. Based upon their outcome, patients were divided into
      two groups: survivors with no need for ECMO, group A (n=8) and survivors
      requiring ECMO or nonsurvivors, group B (n=12). All infants approached or met
      ECMO criteria before NO inhalation. Eight patients (40%) were successfully
      managed with NO and conventional treatment (group A). Newborns in this group
      showed a rapid and sustained improvement of systemic oxygenation during NO
      inhalation. Mean arterial oxygen tension (Pa,O2) increased significantly from 4.5
      kPa (34 mmHg) (95% confidence interval (95% CI) 1.9-7.1 kPa (14.4-53.7 mmHg)) to
      10.1 kPa (75.7 mmHg) (95% CI 6.5-13.6 kPa (49.1-1023 mmHg)) after 1 h and was 9.0
      kPa (67.7 mmHg) (95% CI 7.1-11.0 kPa (53.1-82.4 mmHg)) at 24 h. Conversely, none
      of the oxygenation parameters improved in the 12 patients who ultimately required
      ECMO or died (group B). The results indicate that inhaled nitric oxide can
      improve systemic oxygenation in newborns with acute respiratory failure and may
      reduce the need for extracorporeal membrane oxygenation support in candidates.
      Lack of a rapid response to nitric oxide may be an early predictor of
      unfavourable short-term outcome, prompting a move towards alternative treatments.

PMID- 9551742
TI  - Catalase, myeloperoxidase and hydrogen peroxide in cystic fibrosis.
AB  - An oxidant-antioxidant imbalance with damaging consequences for the bronchial
      epithelium has been hypothesized in the airways of patients with cystic fibrosis
      (CF). It is based on the assumption that neutrophils entering the lumen of the
      infected airways undergo activation and release toxic oxygen metabolites and
      myeloperoxidase (MPO), an enzyme which transforms hydrogen peroxide (H2O2) into
      highly toxic oxygen metabolites. Our aims were to substantiate this hypothesis.
      H2O2 levels were measured in breath condensates of 63 CF patients and 51 normal
      subjects. In CF sputum samples, activities and concentrations of MPO and catalase
      (CAT) were determined. MPO/H2O2-mediated cytotoxicity of CF sputum was measured
      in cell culture assays. H2O2 levels were similar in CF patients and normal
      subjects (mean +/-SD) 0.97 +/- 0.69 versus 1.11+/-0.78 microM; p=0.427).
      Concentrations and activities of CAT (0.31+/-0.18 microM; 105+/-69 units) and MPO
      (5.93+/-4.8 microM; 87.8+/-75 units) were detectable in 38 CF sputa. Addition of
      H2O2 to in vitro cells preincubated with CF sputum did not induce cytotoxicity
      even when CAT was removed from sputum. Sputum MPO together with H2O2 did not
      inactivate alpha-proteinase inhibitor. Preincubation of MPO with sulphated
      glycoconjugates or deoxyribonucleic acid (DNA) totally inhibited its cytotoxic
      effect. In conclusion, catalase, sulphated glycoconjugates and deoxyribonucleic
      acid may prevent myeolperoxidase-mediated oxygen radical generation in cystic
      fibrosis sputum.

PMID- 9551743
TI  - Hydrogen peroxide-induced epithelial injury: the protective role of intracellular
      nonprotein thiols (NPSH).
AB  - Injury to the alveolar region is a hallmark of the adult respiratory distress
      syndrome (ARDS) whereas injury to the epithelium of the conducting airways is a
      characteristic of asthma. Reactive oxygen species have been implicated as
      mediators of lung injury in both of these conditions. We have investigated the
      relationship between intracellular nonprotein thiols (NPSH), and the release of
      the cytosolic enzyme lactate dehydrogenase (LDH), as an index of cell injury,
      following treatment of the human alveolar type II-like epithelial cell line (A549
      cells) or the human bronchial epithelial cell line (16HBE140-) with hydrogen
      peroxide (H2O2). We have also assessed the protective effects of pre-incubation
      of both of these cells lines with H2O2 or enhancement of intracellular NPSH
      against H2O2-induced cell injury. Exposure of A549 and 16HBE140- cells to H2O2
      (0.1 mM and 1 mM respectively for 16 h) produced the release of 40% of the total
      cellular LDH. H2O2 exposure produced an initial dose-dependent decrease in NPSH
      in A549 cells, with a subsequent increase to above control values. 16HBE140-
      cells also showed a dose-dependent decrease in NPSH following exposure to H2O2.
      Pretreatment of A549 cells with 0.1 mM H2O2 followed by subsequent exposure to
      H2O2 did not protect against H2O2-induced LDH release in this epithelial cell
      line. Pre-incubation with 2 mM N-acetylcysteine (NAC) increased NPSH but not
      intracellular reduced glutathione and resulted in total inhibition of H2O2
      induced LDH release in both cell types. Pretreatment with reduced glutathione
      protected both cell types against the injurious effects of H2O2, whereas
      glutathione monethyl ester (GSHMEE) only partially protected A549 cells and had
      no effect in 16HBE140- cells. Intracellular cysteine levels were increased in
      both cell lines following NAC exposure but not sufficiently to account for the
      increase in NPSH levels. These observations raise the possibility that a critical
      concentration of nonprotein thiols may be necessary to protect pulmonary
      epithelial cells against hydrogen peroxide-induced injury.

PMID- 9551744
TI  - Hypoxia reduces endothelin production by rat alveolar type II cells in primary
      culture.
AB  - The purpose of the study was to describe endothelin (ET) production and to
      characterize the effect of hypoxia on preproendothelin-1 (preproET-1) messenger
      ribonucleic acid (mRNA) expression and ET secretion by rat type II pneumocytes in
      vitro. Rat type II pneumocytes were incubated in a sealed chamber containing a
      normoxic (21% O2) or hypoxic (1% O2) atmosphere for increasing durations.
      Immunoreactive ET (irET) was measured in cell supernatants using a
      radioimmunoassay. Rat preproET-1 mRNA was detected by Northern blot. Rat type II
      pneumocytes expressed preproET-1 mRNA, contained irET and secreted irET in a time
      dependent manner. ET secretion was dependent on de novo ribonucleic acid (RNA)
      and protein synthesis. Hypoxia decreased irET secretion by 27% and reduced the
      steady-state level of preproET-1 mRNA by 60% whereas intracellular irET
      concentration was unchanged. Inhibition was partially reversible with the return
      to a normoxic atmosphere. Inhibition of nitric oxide synthesis did not prevent
      the inhibitory effect of hypoxia. In conclusion, rat type II pneumocytes in
      primary culture secreted immunoreactive endothelin and expressed preproendothelin
      1 messenger ribonucleic acid. Hypoxia reversibly reduced endothelin-1 production
      through a reduction of the steady-state preproendothelin-1 messenger ribonucleic
      acid level. Nitric oxide synthesis did not mediate the inhibitory effect of
      hypoxia.

PMID- 9551745
TI  - Integrin dependent migration of lung cancer cells to extracellular matrix
      components.
AB  - Since tumour progression is dependent on the ability of malignant cells to
      interact with the extracellular matrix (ECM), we have investigated the
      significance of beta1 and beta3 integrins for migration of lung cancer cells to
      components of the ECM. In an in vitro hapto- and chemotactic assay system, five
      cell lines representing the major types of lung cancer were examined:
      adenocarcinoma (WART); squamous cell carcinoma (U-1752); small cell lung cancer
      (SCLC) (U-1906, 054 A) and large cell lung cancer (LCLC) (U-1810). Flow
      cytometric analyses were performed to characterize their integrin expression. U
      1906, 054 A, WART and U-1752 all expressed beta1 integrins whereas U-1810 did
      not. However, U-1810 and U-1752 expressed beta3 integrins. All cell lines except
      U-1810 and U-1752 showed hapto- and chemotactic motility to fibronectin, laminin
      and type IV collagen and this motility was beta1 integrin-dependent except in the
      case of U-1810. However, the hapto- and chemotactic responses differed markedly
      between the separate cell lines and there was no distinct pattern to separate non
      small cell lung cancer (NSCLC) from SCLC. No or very little migration was seen in
      control experiments with bovine serum albumin (BSA) or serum-free medium alone,
      indicating that the migration of the lung cancer cells require adhesion
      molecules, soluble or substratum bound. We have found the involvement of beta1
      integrins in lung cancer cell migration in vitro towards fibronectin, laminin and
      type IV collagen except in the case of U-1810. The U-1810 cell line clearly
      differed from the rest of the cell lines by lacking expression of beta1
      integrins.

PMID- 9551746
TI  - Acute effects of deep diaphragmatic breathing in COPD patients with chronic
      respiratory insufficiency.
AB  - This study investigated the impact of deep diaphragmatic breathing (DB) on blood
      gases, breathing pattern, pulmonary mechanics and dyspnoea in severe hypercapnic
      chronic obstructive pulmonary disease (COPD) patients recovering from an acute
      exacerbation. Transcutaneous partial pressure of carbon dioxide (Ptc,CO2) and
      oxygen (Ptc,O2) and arterial oxygen saturation (Sa,O2), were continuously
      monitored in 25 COPD patients with chronic hypercapnia, during natural breathing
      and DB. In eight of these patients, breathing pattern and minute ventilation
      (V'E) were also assessed by means of a respiratory inductance plethysmography. In
      five tracheostomized patients, breathing pattern and mechanics were assessed by
      means of a pneumotachograph/pressure transducer connected to an oesophageal
      balloon. Subjective rating of dyspnoea was performed by means of a visual
      analogue scale. In comparison to natural breathing deep DB was associated with a
      significant increase in Ptc,O2 and a significant decrease in Ptc,CO2, with a
      significant increase in tidal volume and a significant reduction in respiratory
      rate resulting in increased V'E. During DB, dyspnoea worsened significantly and
      inspiratory muscle effort increased, as demonstrated by an increase in
      oesophageal pressure swings, pressure-time product and work of breathing. We
      conclude that in severe chronic obstructive pulmonary disease patients with
      chronic hypercapnia, deep diaphragmatic breathing is associated with improvement
      of blood gases at the expense of a greater inspiratory muscle loading.

PMID- 9551747
TI  - Partitioning of the elastic work of inspiration in patients with COPD during
      exercise.
AB  - During exercise, dynamic hyperinflation-induced intrinsic positive end-expiratory
      pressure (PEEPi) and decreased dynamic lung compliance (CL,dyn) of patients with
      chronic obstructive pulmonary disease (COPD) increase the elastic work of
      inspiration (Wi) more than would be predicted from the increase in tidal volume
      (VT). This contributes significantly to their exertional breathlessness. In 10
      stable patients with COPD, the dynamic Wi was measured during incremental bicycle
      exercise to exhaustion. The total Wi was then partitioned into the portion
      required to overcome PEEPi (Wi,PEEPi) and nonPEEPi elastic load (Wi,nonPEEPi).
      The latter is used to overcome the increase in the total respiratory system
      elastance during inflation. From resting breathing to peak exercise, Wi more than
      doubled (p<0.001). This increase was largely due to Wi,PEEPi, which significantly
      rose from 1.7+/-0.3 to 5.3+/-0.8 L x cm H2O(-1) (p<0.001). In comparison,
      Wi,nonPEEPi increased from only 3.0+/-0.4 to 5.1+/-0.5 L x cm H2O(-1) (p<0.01).
      Consequently, Wi,PEEPi as a fraction of total Wi increased from 35.5+/-5.6 to
      51.0+/-3.3% (p<0.02). In addition, the measured Wi,nonPEEPi at peak exercise,
      when expressed as a percentage of its value during resting breathing, was 25%
      more than that predicted from the increase in VT alone. Assuming a constant chest
      wall compliance, this can be attributed to the exercise-induced decrease in
      CL,dyn, which was 0.27+/-0.04 and 0.17+/-0.02 L x cm H2O(-1) (p<0.01),
      respectively, during resting breathing and peak exercise. In conclusion, the
      dynamic hyperinflation-induced intrinsic positive end-expiratory pressure is more
      important than the increase in tidal volume in raising the work of inspiration
      during exercise in patients with chronic obstructive pulmonary disease; the
      decrease in dynamic lung compliance plays a definite but less important role.

PMID- 9551748
TI  - Effects of proportional assist ventilation on exercise tolerance in COPD patients
      with chronic hypercapnia.
AB  - This study investigates the impact of proportional assist ventilation (PAV), a
      new mode of partial ventilatory support, on exercise tolerance and breathlessness
      in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients. We
      also examined the effects of continuous positive airway pressure (CPAP) and
      pressure support ventilation (PSV). On two consecutive days, 15 stable
      hypercapnic COPD patients underwent four endurance tests on a cycle ergometer at
      80% of their maximal workrate, receiving, via a nasal mask in random order,
      either: 1) sham ventilation (CPAP: 1 cmH2O); 2) CPAP (6 cmH2O); 3) PSV
      (inspiratory pressure support: 12-16 cmH2O; expiratory positive airway pressure
      (EPAP): 1 cmH2O); or 4) PAV (8.6+/-3.6 cmH2O x L(-1) and 3+/-1.3 cmH2O x L(-1)x
      s(-1) of volume and flow assistance, respectively plus EPAP: 1 cmH2O). Oxygen
      supply was standardized to maintain an arterial oxygen saturation (Sa,O2) of 92
      93%. Breathing pattern and minute ventilation (by respiratory inductive
      plethysmography), pulse oximetry, end tidal partial pressure of CO2, cardiac
      frequency and sensations of dyspnoea and leg discomfort (by Borg scale) were
      monitored. In comparison to sham ventilation, PAV, PSV and CPAP were able to
      increase the endurance time (from 7.2+/-4.4 to 12+/-5.6, 10+/-5.2 and 9.6+/-4.6
      min, respectively) and to reduce dyspnoea and oxygen flow to the nasal mask.
      However, the greatest improvement was observed with PAV. We conclude that PAV
      delivered by nasal mask can im-prove exercise tolerance and dyspnoea in stable
      hypercapnic COPD patients and hence this mode of ventilatory support may be
      useful in respiratory rehabilitation programmes.

PMID- 9551749
TI  - Long-term treatment of alpha1-antitrypsin deficiency-related pulmonary emphysema
      with human alpha1-antitrypsin. Wissenschaftliche Arbeitsgemeinschaft zur Therapie
      von Lungenerkrankungen (WATL)-alpha1-AT-study group.
AB  - Alpha1-antitrypsin (alpha1-AT) deficiency is a genetic disorder characterized by
      low serum levels of alpha1-AT and a high risk of pulmonary emphysema at a young
      age. The resulting surplus of proteases, mainly of neutrophil elastase, can be
      balanced by i.v. augmentation with alpha1-AT. However, it is not clear if
      affected patients benefit from long-term augmentation therapy and no long-term
      safety data are available. We examined 443 patients with severe alpha1-AT
      deficiency and pulmonary emphysema receiving weekly i.v. infusions of 60 mg x kg
      body weight(-1) alpha1-AT in addition to their regular medication. The
      progression of the disease was assessed by repeated lung function measurements,
      particularly the decline in forced expiratory volume in one second (deltaFEV1).
      Four hundred and forty three patients with alpha1-AT deficiency tolerated
      augmentation therapy well with few adverse reactions. The deltaFEV1 in 287
      patients with available follow-up data was 57.1+/-31.1 mL x yr(-1). Stratified
      for baseline FEV1, the decline was 35.6+/-21.3 mL in the 108 patients with an
      initial FEV1 <30% and 64.0+/-26.4 mL in the 164 with FEV1 30-65% of predicted
      normal (p=0.0008). The remaining 15 patients had an initial FEV1 >65% pred. Long
      term treatment with i.v. alpha1-antitrypsin in patients with severe alpha1
      antitrypsin deficiency is feasible and safe. The decline in forced expiratory
      volume in one second is related to the initial forced expiratory volume in one
      second as in alpha1-antitrypsin deficient patients not receiving augmentation
      therapy.

PMID- 9551750
TI  - Heart block in patients with obstructive sleep apnoea: pathogenetic factors and
      effects of treatment.
AB  - Heart block during sleep has been described in up to 10% of patients with
      obstructive sleep apnoea. The aim of this study was to determine the relationship
      between sleep stage, oxygen desaturation and apnoea-associated bradyarrhythmias
      as well as the effect of nasal continuous positive airway pressure (nCPAP)/nasal
      bi-level positive airway pressure (nBiPAP) therapy on these arrhythmias in
      patients without electrophysiological abnormalities. Sixteen patients (14 males
      and two females, mean age 49.6+/-10.4 yrs) with sleep apnoea and nocturnal heart
      block underwent polysomnography after exclusion of electrophysiological
      abnormalities of the sinus node function and atrioventricular (AV) conduction
      system by invasive electrophysiological evaluation. During sleep, 651 episodes of
      heart block were recorded, 572 (87.9%) occurred during rapid eye movement (REM)
      sleep and 79 (12.1%) during nonrapid eye movement (NREM) sleep stages 1 and 2.
      During REM sleep, the frequency of heart block was significantly higher than
      during NREM sleep: 0.69+/-0.99 versus 0.02+/-0.04 episodes of heart block x min(
      1) of the respective sleep stage (p<0.001). During apnoeas or hypopnoeas, 609
      bradyarrhythmias (93.5%) occurred with a desaturation of at least 4%. With nCPAP/
      nBiPAP therapy, apnoea/hypopnoea index (AHI) decreased from 75.5+/-39.6 x h(-1)
      to 3.0+/-6.6 x h(-1) (p<0.01) and the number of arrhythmias from 651 to 72
      (p<0.01). We conclude that: 1) 87.9% of apnoea-associated bradyarrhythmias occur
      during rapid eye movement sleep; 2) the vast majority of heart block episodes
      occur during a desaturation of at least 4% without a previously described
      threshold value of 72%; and 3) nasal continuous positive airway pressure or nasal
      bi-level positive airway pressure is the therapy of choice in patients with
      apnoea-associated bradyarrhythmias.

PMID- 9551751
TI  - Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome:
      role of recurrent apnoeas.
AB  - Recent results in animals have suggested that repetition of hypoxaemic stimuli
      may result in a progressive increase in pulmonary arterial pressure (Ppa). The
      purpose of the present study was to investigate the effects of recurrent
      obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of
      Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five
      snorers. Mean Ppa was measured before, at the start, at the end and after the
      selected apnoeas. The analysis was performed for each 1 h period for at least 7 h
      throughout the night on at least 10 randomly selected apnoeas per hour. In
      snorers, 100 randomly chosen values were measured during every hour of the night.
      In the morning after the nocturnal study, the Ppa responses to acute hypoxia and
      hypercapnia were measured. No Ppa changes throughout the 7 h were found during
      sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small
      but significant increase in Ppa throughout the night was noted, affecting the
      values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa
      slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x
      h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When
      we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in
      progressive Ppa was also present, irrespective of changes in apnoea duration and
      apnoea desaturation. The Ppa rise during the night was not affected by diurnal
      Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep
      apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery
      pressure progressively increases during the night, reflecting the cumulative
      effects of apnoeas and nocturnal hypoxaemia.

PMID- 9551752
TI  - Mandibular advancement devices for the control of snoring.
AB  - Patients presenting with the complaint of antisocial snoring have very few
      options available to them of proven efficiency. Mandibular advancement devices
      worn intra-orally at night, have recently been shown in controlled trials to help
      mild to moderate obstructive sleep apnoea. However, there are no properly
      controlled studies with objective measurements on the use of such appliances for
      the management of antisocial snoring. Fifteen patients, already established on
      mandibular advancement devices for the control of snoring, were asked to
      participate in this study. They were studied over two nights, using a portable
      sleep monitoring device at home, both with and without their mandibular
      advancement devices in place (in randomized order). Snoring was measured using a
      surface throat microphone. In addition oxygen saturation and indirect beat to
      beat blood pressure were measured. The latter (using pulse transit time) provided
      an index of autonomic "arousals" and a measure of inspiratory effort. In nearly
      all of these highly selected patients the mandibular advancement devices reduced
      significantly the amount of snoring from a median of 193 to 20 snores x h(-1)
      (p<0.0001). In addition there was a reduction in respiratory effort, implying
      enlargement of the upper airway whilst wearing the appliance. These patients only
      represent those who were able to tolerate the appliance. With such clear evidence
      of their potential efficacy, and no suggestion from other studies of any harm, it
      would seem reasonable to introduce this approach into the management of
      antisocial snoring.

PMID- 9551753
TI  - Normative data on snoring: a comparison between younger and older adults.
AB  - Snoring is a common sleep-related behaviour. Increased body mass index (BMI),
      cranio-facial anatomical features, and older age have been linked to the
      occurrence of snoring. While mostly middle-aged populations have been studied for
      the occurrence of snoring and sleep-related breathing abnormality, this study was
      designed to assess the subjective report of snoring and the objective measurement
      of snoring at the two extremes of human age. The study design called for
      measurement of snoring in two age groups (college students; n=155 and older
      subjects; mean age 64.1 yrs n=134) with a mean age difference of 45 yrs. Snoring
      was assessed with a validated recording device. A validated questionnaire was
      used to subjectively assess snoring and obtain relevant sleep-related
      information. Students and older subjects differed in the self-report of snoring.
      While 83% of students reported "never" or "rarely" snoring only 35% of older
      subjects fell into these categories. Measurement of snoring during sleep revealed
      that students spent more time during sleep with continuous snoring than older
      subjects. In older subjects, a reduction in continuous snoring was accompanied by
      an increase in apnoeic snoring. Subjective snoring frequency correlated with
      continuous snoring in students only. A positive family history of snoring
      increased the odds ratio for self-reported snoring but not for recorded snoring.
      It has been shown that snoring frequency can vary depending on age and that the
      congruency between perceived snoring frequency and recorded snoring is influenced
      by the age of an individual.

PMID- 9551754
TI  - Validation of automated sleep analysis in normal children.
AB  - With the aim of determining normal reference values for our sleep laboratory and
      evaluating the reliability of automated analysis for scoring polysomnographic
      studies in children, we recorded polysomnograms in 16 healthy boarding-school
      children. Sleep recordings were obtained with a computer system (Medilog SAC,
      Oxford Instruments). Polysomnographic variables were monitored continuously on a
      16-channel recorder equipped with a video. Data were acquired on optical disk for
      computer-assisted data interpretation. Sleep stages and respiratory events were
      also scored visually by operator. Comparison with visual scores showed that the
      computer system significantly overscored wakefulness (W) (p<0.02) and stage IV
      (p<0.001) and underscored stage II (p<0.001) and rapid eye movement (REM) sleep
      (p<0.001). It also assigned respiratory events a higher score than did visual
      scoring, as shown by the higher apnoea index (AI) and hypopnoea index (HI) (AI
      p<0.03; HI p<0.001). Regression analysis showed a significant correlation between
      visual and automated scores for central (r=0.679; p<0.004) and obstructive apnoea
      (r=0.631; p<0.008). Computer apnoea scores did not correlate with visual scores.
      Much remains to be done before computer-based scoring systems can be relied upon,
      without visual scoring, for polysomnographic sleep studies in children. Their
      main advantage at present is that they offer a convenient means of saving paper,
      space and time.

PMID- 9551755
TI  - Subjective scoring of cough in children: parent-completed vs child-completed
      diary cards vs an objective method.
AB  - Cough is often used as an outcome measure, although the reporting of cough is
      unreliable. Using a 24 h ambulatory cough meter to measure cough frequency, the
      aim of this study was to compare: 1) the correlation of child-completed diary
      cards to the objective measurement, with that of parent-completed diary cards;
      and 2) the visual analogue scale (VAS) to the verbal category descriptive (VCD)
      score. The cough meter consisted of a previously validated Holter monitor and a
      cough processor. Eighty four children (39 with recurrent cough and 45 controls,
      aged 6-17 yrs) used a cough meter at least once. Thirty three subjects used the
      cough meter twice. Parents and children completed separate diary cards using the
      VAS and VCD scores. The strength of the relationship between the subjective
      scores and the objective recordings was analysed by spearman's rank correlation
      coefficient. For daytime cough, child-completed diary cards and the VCD
      correlated better to the objective measurement than parent-completed diary cards
      and the VAS, respectively. In subjects that used the cough meter twice, the
      difference between the cough frequency correlated to the difference in the
      subjective scores. The confidence intervals for the correlation coefficients were
      wide. The agreement between the objective and subjective presence of daytime
      cough was good but that for night-time cough was poor. We conclude that the
      severity of cough defined on diary cards may not represent cough frequency.
      Objective readings are first choice but currently not yet practical. The verbal
      category descriptive diary card completed by children and assisted by parents has
      the highest correlation to cough frequency measured objectively.

PMID- 9551756
TI  - Exhaled single-breath nitric oxide measurements are reproducible, repeatable and
      reflect levels of nitric oxide found in the lower airways.
AB  - Measurement of exhaled nitric oxide (NO) may allow noninvasive assessment of
      inflammatory disease in the lung. We determined immediate and day-to-day
      reproducibility of single-breath NO measurements at different points on the
      exhaled test, and whether levels recorded reflect levels of NO in the lower
      airways. Using a rapid chemiluminescence analyser, 55 healthy control subjects
      performed three sequential tests on each of two days. NO levels were compared at
      the level corresponding with: 1) the time the mouth pressure fell below 4 cmH2O
      (MP); 2) the plateau of end-exhaled CO2 (CO2); and 3) the NO plateau (NOp). NO
      levels were measured directly from the lower airways of 15 lung transplant
      recipients and compared with NO levels from a single-breath test performed in the
      same cohort. For measurements performed at MP, CO2 and NOp, the mean +/- SD
      differences between the two closest levels performed on the same day were 0.11+/
      0.18, 0.095+/-0.16 and 0.094+/-0.13 parts per billion (ppb), respectively, and
      between days were 0.18+/-0.76, 0.19+/-0.78 and 0.17+/-0.8 ppb, respectively. End
      expiratory levels recorded at the mouth from a single-breath test and in the
      lower airways were highly correlated (mouth versus trachea r2=0.95, p<0.0001,
      mouth versus bronchus r2=0.92, p<0.0001). Single-breath exhaled nitric oxide
      levels are a simple, reproducible and valid measure of nitric oxide production
      from the lower respiratory tract.

PMID- 9551757
TI  - Nicotine replacement: a new approach to reducing tobacco-related harm.
AB  - Primary prevention is usually regarded as the most desirable goal in efforts to
      control tobacco-related diseases. However, this has not been very effective so
      far; moreover, it would take 30-40 yrs for primary prevention to translate into
      major health benefits. Modification of tobacco products and/or reduction of
      tobacco use may also have some impact on tobacco-related diseases. A tobacco dose
      dependent risk has been observed in these diseases, including cancer,
      cardiovascular diseases, chronic nonspecific respiratory disorders, and problems
      during pregnancy. Reduced smoking (smoking fewer cigarettes, leading to a reduced
      intake of toxic substances) may be indicated in individuals who: 1) are failing
      in cessation attempts; 2) want to quit but are unable to do so; and 3) do not
      want to quit but want to reduce smoking. Studies have shown that nicotine
      replacement medications may be an untapped source in efforts to reduce smoking.
      Based on Austrian data, it is estimated that, approximately 10 yrs after
      implementation, a 1% reduction in smoking could save 14 male lung cancer deaths
      each year, and a 50% reduction would save 700 male lives. Inclusion of females
      and other tobacco-related diseases suggest that thousands of lives could be saved
      if smoking could be reduced by 50%. In the European Union, such a reduction in
      smoking could save > or = 100,000 lives annually. Even a 1% reduction would save
      1,000 lives. In conclusion, reduced smoking should be explored as a valid method
      of reducing tobacco-related harm in those unwilling or unable to quit smoking.

PMID- 9551758
TI  - Current opinion of muco-active drug research: strategies and problems.
AB  - In general, mucoactive drugs are classified into several groups. However, since
      many drugs have overlapping effects, it is difficult to classify the drugs into
      groups based on their major actions. It has been reported that many mucoactive
      drugs have antioxidant effects. It is reasonable to suggest that an anti
      inflammatory property is crucial to demonstrate effectiveness in a clinical
      context. From this point of view, we have evaluated several mucoactive drugs over
      two decades. Of these, we will consider the following drugs with anti
      inflammatory properties: sodium aceneuramate; glucocorticoids; traditional
      Chinese medicines; and new cysteine derivatives. On the basis of these findings,
      we believe that the efforts to seek for compatible actions between
      glucocorticoids and oriental medicines may provide new opportunities for
      development of ideal mucoactive drugs with specified actions, i.e. suppression of
      gene expression.

PMID- 9551759
TI  - Respiratory muscles as a target for adenovirus-mediated gene therapy.
AB  - The protein dystrophin is absent in the muscles of patients with Duchenne
      muscular dystrophy (DMD) as well as dystrophin-deficient mice with muscular
      dystrophy (mdx mice). The mdx mouse diaphragm closely resembles the human DMD
      phenotype and thus provides a useful model for studies of dystrophin gene
      replacement. Recombinant adenovirus vectors (AdVs) hold promise as a means for
      delivering a functional dystrophin gene to muscle. As an initial step toward this
      goal, we have determined the efficiency and functional consequences of AdV
      mediated reporter gene transfer to the diaphragm in both normal and mdx adult
      mice. At 1 week after AdV administration, there was a high level of transgene
      expression in the diaphragm. One month later, however, elimination of transgene
      expression was observed along with a significant decrease in force production by
      both normal and mdx diaphragms. Immunosuppression with cyclosporine did not
      augment the level of transgene expression, but a beneficial effect on diaphragm
      force-generating capacity was observed in both groups of animals. In order to
      further elucidate the cellular mechanisms underlying these findings, the effects
      of AdV gene inactivation (by ultraviolet (UV) irradiation) and interference with
      host T-lymphocyte subsets were examined. Both UV-inactivation of AdV and CD8+ T
      cell deficiency were found to significantly alleviate AdV-induced reductions in
      diaphragm force-generating capacity. Brief (2 day) administration of a
      neutralizing antibody against host CD4+ T-cells also produced a trend towards
      mitigation of AdV-induced contractile dysfunction. In addition, transgene
      expression one month after AdV delivery was significantly enhanced with
      inhibition of either CD4+ or CD8+ T-cell function. The data suggest two major
      sources of reduced force generation after recombinant adenovirus vector-mediated
      gene transfer to muscle: 1) a cytotoxic component associated with recombinant
      adenovirus vector transcriptional activity; and 2) an immune-based component of
      more delayed onset that is primarily dependent upon CD8+ T-cell activity. These
      results have important implications for the design of future generation vectors
      and the potential need for immunosuppressive therapy after recombinant adenovirus
      vector mediated dystrophin gene transfer to Duchenne muscular dystrophy patients.

PMID- 9551760
TI  - Functional upper airway obstruction and chronic irritation of the larynx.
AB  - Wheezing and dyspnoea are typical symptoms of asthma but can also be found in
      diseases of the extrathoracic airways. Functional upper airway obstruction may
      imitate, as well as complicate asthma. Functional upper airway obstruction was
      first described as a conversion disorder in young females with inspiratory
      stridor. Subsequently, it was found that functional upper airway obstruction was
      more often a secondary phenomenon in chronic asthma also involving the expiratory
      laryngeal airflow. During a period of 15 months, we diagnosed six cases of
      functional upper airway obstruction. Five patients were female and one male, and
      four were also asthmatics. Three cases showed chronic sinusitis with postnasal
      drip (PND) and/or gastro-oesophageal reflux. Both disorders may irritate the
      larynx. Treatment of sinusitis and gastro-oesophageal reflux led to a significant
      improvement of dyspnoea in all three of these patients. In asthma refractory to
      treatment and in the case of an asthmatic exacerbation without obvious cause,
      functional upper airway obstruction should be excluded to avoid unnecessary
      treatment with systemic steroids. Some of the possible causative factors of
      functional upper airway obstruction, such as postnasal drip and gastro
      oesophageal reflux, are easily treatable.

PMID- 9551761
TI  - Early-onset phenytoin toxicity mimicking a renopulmonary syndrome.
AB  - Phenytoin is a commonly used anti-epileptic drug. Adverse reactions including
      fever, skin reactions and lymphadenopathy are well known but atypical reactions
      can also occur. A patient is described with a lag time of only 4 days between
      onset of phenytoin and the development of a syndrome with acute lung injury and
      renal failure. The symptoms mimicked a renopulmonary syndrome, and resolved
      completely after cessation of phenytoin and addition of steroids.

PMID- 9551762
TI  - Diffuse alveolar damage in a patient treated with gemcitabine.
AB  - We present a case of diffuse alveolar damage (DAD) that occurred in a male aged
      68 yrs treated with gemcitabine, a novel antineoplastic agent, that was given for
      hepatic relapse of a previously resected non-small cell lung cancer. The patient
      developed acute respiratory failure after the sixth drug dose, and died 4 days
      after admission. Autopsy revealed a pattern of DAD. No evidence of infection or
      other specific aetiologies could be found. To our knowledge, only three cases of
      pulmonary toxicity resulting from treatment with gemcitabine have been published;
      two of them were fatal and postmortem examination revealed a pattern consistent
      with acute respiratory distress syndrome. A careful survey may determine the
      incidence of pulmonary toxicity of this new drug in the future.

PMID- 9551763
TI  - Rapidly progressing pulmonary nodules in a 14 yr old boy.

PMID- 9551764
TI  - Treatment of spontaneous pneumothorax--an ongoing debate.

PMID- 9551765
TI  - Deramciclane, a putative anxiolytic drug, is a serotonin 5-HT2C receptor inverse
      agonist but fails to induce 5-HT2C receptor down-regulation.
AB  - Deramciclane (EGIS-3886) is a novel anxiolytic agent that binds with high
      affinity to 5-HT2A/2C receptors. The interactions of deramciclane with the
      serotonin 5-HT2C receptor were characterized further using receptor
      phosphoinositide hydrolysis assays and receptor autoradiography. Deramciclane
      antagonized 5-HT2C receptor mediated 5-HT-stimulated phosphoinositide hydrolysis
      with an IC50 value of 168 nM. Deramciclane also decreased basal phosphoinositide
      hydrolysis by up to 33% (EC50 = 93 nM) in a physiological system in the choroid
      plexus, suggesting that deramciclane possesses inverse agonist properties at this
      receptor. Administration of single doses of 0.5 mg/kg and 10 mg/kg resulted in a
      maximal 5-HT2C receptor occupancy of up to 45% and 79%, respectively, in the
      choroid plexus. Chronic (14 days) treatment with 0.5 mg/kg or 10 mg/kg
      deramciclane did not alter [125I]DOI (agonist) or [3H]mesulergine (antagonist)
      binding to 5-HT2C receptors in the choroid plexus compared to saline-treated
      controls, as determined by quantitative receptor autoradiography. In comparison,
      the effects of deramciclane on 5-HT2A binding characteristics and receptor
      occupancy were also studied. Deramciclane treatment resulted in 5-HT2A receptor
      occupancy of up to 78%, but no significant effect of chronic treatment on 5-HT2A
      receptor agonist binding levels was found. In conclusion, these data indicate
      that deramciclane is a 5-HT2C receptor inverse agonist and occupies 5-HT2C
      receptors during treatment, and that chronic treatment with deramciclane does not
      lead to 5-HT2C receptor down-regulation.

PMID- 9551766
TI  - Interactions between intra-perifornical region sulpiride and intra-ventral
      tegmental area AP5 on measures of locomotor activity and conditioned place
      preference.
AB  - Infusions of sulpiride, a dopamine D2/D3 receptor antagonist within the
      perifornical region of the lateral hypothalamus have been shown previously to
      exhibit a behavioural profile generally attributed specifically to activation of
      the mesoaccumbens dopamine projection. Experiment 1 confirmed previous work
      showing that repeated homecage pretreatment with sulpiride (5 microg) in the
      perifornical region of the lateral hypothalamus resulted subsequently in an
      enhanced locomotor response to a d-amphetamine challenge. Experiment 2 examined
      the possibility that the observed behavioural changes were due to stimulation of
      the mesoaccumbens dopamine projection via the ventral tegmental area. Thus,
      repeated intra-perifornical infusions with sulpiride were without effect
      initially, but resulted in a gradual increase in locomotor activity during
      subsequent sessions. Intra-ventral tegmental area infusions of the NMDA receptor
      antagonist AP5 (0.3, 1.0 nmol) were without intrinsic effect upon locomotor
      activity at any time. However, AP5 blocked the ability of repeated sulpiride
      infusions to increase locomotor activity, and the ability of intra-perifornical
      sulpiride to support the acquisition of a conditioned place preference. AP5
      sulpiride co-infusions also increased locomotor activity in a non-incremental
      manner. These data suggest there to be a functionally significant projection from
      the perifornical region of the lateral hypothalamus to the ventral tegmental area
      in the control over locomotor activity and rewarded behaviour.

PMID- 9551767
TI  - The effects of selected antidepressant drugs on timing behaviour in rats.
AB  - It has been suggested that the increased reinforcement rate on a differential
      reinforcement-of-low-rate of responding (DRL) schedule observed following acute
      antidepressant administration in the rat is due to an improvement in timing
      accuracy. The aim of the present work was to evaluate the effects of
      antidepressants in another schedule that requires accurate estimation of time
      intervals, the peak procedure. Three antidepressant drugs were tested, the
      tricyclic antidepressant imipramine (1.0-10.0 mg/kg, i.p.) and the 5-HT reuptake
      inhibitors, zimelidine (10.0-40.0 mg/kg, i.p.) and clomipramine (1.0-10.0 mg/kg,
      i.p.). For reference, the full benzodiazepine receptor agonist, diazepam (1.0-5.0
      mg/kg, i.p.) and the psychomotor stimulant, d-amphetamine (0.5-1.5 mg/kg, s.c.)
      were also tested. All doses of d-amphetamine tested significantly increased lever
      pressing rates, whereas all the other compounds induced significant decreases in
      lever-pressing rates. Overall, the time at which the maximal lever-pressing rate
      occurred was not altered by any of the compounds, suggesting that timing accuracy
      was not significantly affected by any of the compounds administered. The only
      exception was zimelidine (40.0 mg/kg), which reduced the time at which the
      maximal lever-pressing rate occurred, although lever-pressing rates were also
      significantly reduced at this dose. These data suggest that previously reported
      antidepressant-induced improvement in performance on the DRL schedule may not
      have been due to improved timing accuracy per se but may have been due to a
      decrease in lever-pressing rates.

PMID- 9551768
TI  - Effects of AMPA receptor antagonists on dopamine-mediated behaviors in mice.
AB  - Current data indicate that dopaminergic and glutamatergic neurotransmitter
      systems interact. The role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA) glutamate receptor subtypes in modulating dopamine neurotransmission,
      however, remains unclear. The noncompetitive AMPA antagonists, GYKI 52466 (5-40
      mg/kg) and LY300164 (1-6 mg/kg), and the competitive AMPA antagonists, LY326325
      (5-80 mg/kg) and NBQX (10-80 mg/kg), were compared to the dopamine antagonist,
      haloperidol (0.03-1.0 mg/kg), for their ability to inhibit dopamine-mediated
      behaviors after i.p. administration in mice. The behavioral paradigms included
      amphetamine- or dizocilpine-induced hyperactivity, amphetamine-induced
      stereotyped sniffing, and apomorphine-induced climbing and stereotyped sniffing.
      All four AMPA antagonists and haloperidol attenuated amphetamine- and dizocilpine
      induced hyperactivity and decreased spontaneous locomotion. Haloperidol and GYKI
      52466 were more potent against amphetamine than against dizocilpine. In contrast,
      LY326325 was more potent against dizocilpine than against amphetamine. The
      hyperactivity decreases by LY300164 and NBQX were most likely due to non-specific
      effects on motor behavior. The AMPA antagonists and haloperidol also attenuated
      amphetamine- induced stereotypy. Unlike haloperidol, however, GYKI 52466,
      LY300164, and NBQX failed to attenuate apomorphine-induced climbing and
      stereotyped sniffing. LY326325, on the other hand, attenuated apomorphine-induced
      stereotypy, but not climbing. These results indicate that AMPA receptor
      antagonists can attenuate the behavioral effects of drugs, such as amphetamine
      and dizocilpine, that increase dopamine neurotransmission. However, the
      behavioral effects of the direct dopamine agonist apomorphine are not
      consistently attenuated by AMPA antagonists. The competitive AMPA receptor
      antagonist LY326325 appears to have a profile distinct from both haloperidol and
      the other AMPA antagonists tested.

PMID- 9551769
TI  - Methamphetamine modulates GABA-induced electrophysiological depression by
      alternating noradrenergic actions in cerebellar Purkinje neurons.
AB  - Previous studies have indicated that gamma-aminobutyric acid (GABA)-induced
      electrophysiological responses can be enhanced by noradrenaline (NE) acting via
      beta-adrenergic receptors. Methamphetamine (MA) has been reported to be a
      noradrenergic releasing agent. In the present study, we examined the interaction
      of MA and GABA in cerebellar Purkinje neurons of urethane-anesthetized rats. We
      found that local application of MA did not potentiate GABA-induced
      electrophysiological depressions in Purkinje neurons. Since MA may act indirectly
      or directly on alpha or beta noradrenergic receptors, we further examined the
      interactions of MA with selective noradrenergic antagonists. We found that after
      blocking alpha-adrenergic receptors with prazocin, MA significantly facilitated
      GABA responses. On the other hand, co-administration of timolol with MA did not
      attenuate GABA-induced neuronal depressions. To examine further the interactions
      between alpha and beta receptors in modulating GABA response, we found that
      stimulation of alpha-adrenergic receptors in the absence of beta receptor
      activation, such as by application of the alpha-agonist phenylephrine alone, did
      not decrease GABA-induced inhibition. However, stimulation of alpha-adrenergic
      receptors in the presence of beta-receptor activation, such as by co-application
      of phenylephrine and the beta-agonist isoproterenol (ISO), attenuated ISO
      facilitated GABA inhibition. Taken together, these data suggest that MA may
      activate two noradrenergic modulatory mechanisms: beta-adrenergic receptor
      induced GABA potentiation and alpha-adrenergic inhibition, which attenuates beta
      mediated modulation. In conclusion, our data suggest that MA may regulate GABA
      induced electrophysiological response by altering both the alpha- and beta
      noradrenergic inputs in cerebellar Purkinje neurons.

PMID- 9551770
TI  - Further evaluation of the reinforcing effects of the novel cocaine analog 2beta
      propanoyl-3beta-(4-tolyl)-tropane (PTT) in rhesus monkeys.
AB  - 2Beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) is a cocaine analog which has been
      shown in rhesus monkeys to have cocaine-like discriminative stimulus effects and
      a long duration of action (>8 h), yet does not function as a reinforcer when
      substituted for cocaine in monkeys responding under a fixed-interval 5-min
      schedule (Nader et al. 1997). The purpose of the present study was to evaluate
      the reinforcing effects of PTT under a fixed-ratio (FR) schedule and to determine
      if decreasing the inter-injection interval would influence the reinforcing
      effects of PTT. Male rhesus monkeys (n=3) were trained to respond under a
      multiple FR 30 food-drug-food schedule. When responding was stable, cocaine
      (0.003-0.3 mg/kg per injection) or PTT (0.001-0.03 mg/kg per injection) was
      available during the drug component for at least five consecutive sessions and
      until stable responding was observed. To investigate whether the inter-injection
      interval would influence PTT-maintained response rates, the time-out (TO)
      following PTT injections was reduced from 180 or 300 s to 10 s for at least five
      consecutive sessions. Cocaine-maintained response rates were characterized as an
      inverted-U shaped function of dose, with peak rates maintained by 0.03 mg/kg per
      injection cocaine. PTT (0.001-0.03 mg/kg per injection) maintained response rates
      significantly higher than rates maintained by the PTT vehicle, but significantly
      lower than cocaine-maintained response rates; PTT intake increased with a dose. A
      reduction of the TO following PTT injections to 10 s did not alter PTT-maintained
      response rates or total session intake. Self-administered PTT was more potent
      than cocaine at decreasing food-maintained responding. These results suggest that
      for long-acting compounds like PTT, reinforcing effects are more likely to be
      observed when the drug is available under a ratio-based schedule, compared to an
      interval-based schedule.

PMID- 9551771
TI  - Anxiolytic activity of ginkgolic acid conjugates from Indian Ginkgo biloba.
AB  - Ginkgolic acid conjugates (GAC) (6-alkylsalicylates, namely n-tridecyl-, n
      pentadecyl-, n-heptadecyl-, n-pentadecenyl- and n-heptadecenylsalicylates)
      isolated from the leaves of Indian Ginkgo biloba Linn., (IGb) were tested for
      their putative role in anxiety in rats. Elevated plus maze, open-field behaviour,
      novelty-induced feeding latency and social interaction were the rodent
      behavioural models used in this study. GAC (0.3 and 0.6 mg/kg, each, p.o.) on
      single acute administration, showed dose-related changes in the behaviour. GAC
      (0.6 mg/kg) and DZ augmented open arm entries, the open arm/closed arm entries
      ratio and increased time spent in the open arm on the elevated plus maze. In the
      open field, GAC (0.6 mg/kg) and DZ significantly increased ambulation and reduced
      the immobility time. EGb 761 showed a similar profile. GAC (0.6 mg/kg) and DZ
      significantly attenuated the increased latency to feed in novel environment. By
      contrast, EGb 761 and Ginkocer further augmented feeding latency. None of the
      drugs tested showed any significant effect in the social interaction test. GAC
      showed consistent and significant anxiolytic activity in all the variables
      investigated. By contrast, EGb 761 and Ginkocer, which are devoid of GAC, did not
      evoke significant activity. However, increased rearing and decreased immobility
      time only in open field behaviour shown by EGb 761 may be due to some antianxiety
      activity of a lesser degree. Our observations suggest that GAC may be the active
      constituents of Ginkgo biloba responsible for the anxiolytic activity.

PMID- 9551773
TI  - Strychnine effects on ultrasound-elicited behaviours in Lister hooded rats.
AB  - Previous studies have demonstrated that Lister hooded rats will exhibit
      characteristic bursts of locomotion when exposed to a 20-kHz acoustic stimulus;
      this ultrasound-induced locomotion has been suggested as a potential model for
      panic attacks. Although ultrasound presentation rarely induces convulsions, the
      locomotor bursts exhibited resemble pre-convulsant running. The present studies
      examined the interactions between strychnine treatment and experimenter-presented
      ultrasounds on behaviour in male Lister hooded rats. Strychnine was selected
      because it is a potent and effective convulsion-inducing agent which is not known
      to induce anxiety in humans. Behaviour in a circular arena (75 cm diameter) was
      observed live, videotaped and traced electronically. In experiments 1 and 2,
      moderate (60 s) or relatively brief (15 s) exposure to an ultrasound stimulus (20
      kHz, 98 dB, SPL) typically resulted in 5- to 10-s bursts of locomotion in saline
      treated subjects; strychnine treatment (0.5, 0.7, 1.0 mg/kg, injected i.p., 10
      min prior to testing) significantly increased this ultrasound-induced locomotion
      in a dose-dependent manner. Experiment 3 demonstrated that the strychnine
      enhancement of the ultrasound response was not different in naive animals when
      compared to those subjects which had received occasional strychnine and/or
      ultrasound treatment previously. Experiment 3 also demonstrated that strychnine
      treatment can cause at least modest running in subjects exposed to a 2 kHz tone
      (96 dB SPL). In experiment 4, exposure to the 20 kHz, 98 dB ultrasound stimulus
      for a much longer period, 9 min, resulted in irregular cycles of bursts of
      locomotion, followed immediately by periods of relative inactivity in saline
      treated animals; approximately 10% of these subjects exhibited tonic-clonic
      convulsions. No convulsions occurred in strychnine-treated subjects during the
      period 10-20 min post-injection in the absence of ultrasound exposure; in
      contrast, the frequency of occurrence of convulsions in strychnine-treated
      subjects (10-20 min post-injection) exposed to the ultrasound stimulus was
      greater than 50%; these convulsions typically occurred at the end of a locomotor
      burst. The results of the present studies suggest that there may be a
      relationship between ultrasound-induced locomotor bursts and convulsant activity.

PMID- 9551772
TI  - Olanzapine increases in vivo dopamine and norepinephrine release in rat
      prefrontal cortex, nucleus accumbens and striatum.
AB  - The in vivo effects of olanzapine on the extracellular monoamine levels in rat
      prefrontal cortex (Pfc), nucleus accumbens (Acb) and striatum (Cpu) were
      investigated by means of microdialysis. Sequential doses of olanzapine at 0.5, 3
      and 10 mg/kg (s.c.) dose-dependently increased the extracellular dopamine (DA)
      and norepinephrine (NE) levels in all three brain areas. The increases appeared
      30 min after olanzapine administration, reached peaks around 60-90 min and lasted
      for at least 2 h. The highest DA increases in the Acb and Cpu were induced by
      olanzapine at 3 mg/kg but at 10 mg/kg in the Pfc. The peak DA increase in the Pfc
      (421% +/- 46 of the baseline) was significantly larger than those in the Acb
      (287% +/- 24) and Cpu (278% +/- 28). Similarly, the highest NE increase in the
      Pfc (414% +/- 40) induced by 10 mg/kg olanzapine was larger than those in the Acb
      (233% +/- 39) and Cpu (223% +/- 24). The DA and NE increases in the Pfc induced
      by olanzapine at 3 and 10 mg/kg (s.c.) were slightly larger than those induced by
      clozapine at the same doses. In contrast, haloperidol (0.5 and 2 mg/kg, s.c.) did
      not change Pfc DA and NE levels. Extracellular levels of a DA metabolite, DOPAC,
      and tissue concentrations of a released DA metabolite, 3-methoxytyramine, were
      also increased by olanzapine, consistent with enhanced DA release. However,
      olanzapine at the three sequential doses did not alter the extracellular levels
      of either 5-HT or its metabolite, 5-HIAA, in any of the three brain areas. In
      conclusion, the present studies demonstrate that in the case of sequential dosing
      olanzapine more effectively enhances DA and NE release in the Pfc than in the
      subcortical areas, which may have an impact on its atypical antipsychotic
      actions.

PMID- 9551774
TI  - The effects of cigarette smoking on overnight performance.
AB  - Fifteen healthy smokers and 15 non-smokers were enrolled into this study
      investigating the effects of smoking on overnight performance. Subjects arrived
      at the test centre at 1930 hours and were assessed at baseline (2000 hours) and
      at 2200, 0000, 0200, 0400, 0600, and 0800 hours on a battery of tests (including
      Critical Flicker Fusion, CFF; Choice Reaction Time, CRT; Compensatory Tracking
      Task, CTT; Short Term Memory Task, STM; and the Line Analogue Rating Scale,
      LARS). Results showed that the performance of the smokers was more consistent
      with baseline measures than that of the non-smokers, which became more impaired
      throughout the night on a number of tasks [CFF (P < 0.005), Total Reaction Time
      (TRT, P < 0.05), CTT (P < 0.05) and the Reaction Time (RT) aspect of the CTT task
      (P < 0.0005)]. The Recognition Reaction Time (RRT) aspect of the CRT task showed
      that the performance of the non-smokers became more impaired from baseline (P <
      0.005), while that of the smokers remained at baseline levels until 0400 hours,
      when it deteriorated to become comparable to that of the non-smoking controls.
      Subjective sedation ratings (LARS) resulted in comparable levels of impairment
      for both study groups (P < 0.00005). Findings from the STM task failed to reach
      significance. These data suggest that when performance is being measured
      overnight, smokers show little or no impairment, whilst the performance of non
      smokers showed performance decrements.

PMID- 9551775
TI  - Cerebral effects of nicotine during cognition in smokers and non-smokers.
AB  - For the smoker, nicotine has a positive effect on attention, cognition and mood.
      Conversely, nicotine abstinence is characterized by uncomfortable psychological
      effects such as impaired attention, but also irritability. We postulated that
      nicotine exerts an effect on cerebral areas important for attention and mood.
      Regional cerebral blood flow (rCBF), as an index for cerebral activity, was
      measured in both smokers and non-smokers. They were scanned during performance of
      a psychometric task with and without i.v. infusion of nicotine (1-methyl-2-[3
      pyridyll] pyrrolidine). Nicotine induced rCBF decreases in the anterior cingulate
      cortex and the cerebellum, and concomitant increases in the occipital cortex. The
      changes were similar in nature and magnitude in smokers and non-smokers. Thus,
      specific changes were induced in areas pertaining to the anterior attention
      system and to higher order visual cortex. We conclude that these effects on
      cerebral activity provide insights into the desired positive effects of nicotine
      on cognition as well as the negative effects experienced during nicotine
      abstinence.

PMID- 9551776
TI  - Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the
      rat forced swimming test.
AB  - Because of clinical interest in the effects of antidepressant drugs that exert
      their effects on multiple neurotransmitter systems, the behavioral effects
      produced by combined treatment with an SSRI (fluoxetine) with a selective
      norepinephrine (NE; desipramine) or dopamine (DA) reuptake inhibitor (buproprion)
      were examined in the forced swimming test (FST), a behavioral test in rodents
      that predicts the clinical activity of antidepressants. Three additional
      compounds with mixed activity as NE-5-HT reuptake inhibitors, milnacipran,
      duloxetine and venlafaxine, were also examined. Desipramine and fluoxetine both
      reduced immobility in the FST, but desipramine increased only climbing behavior,
      whereas fluoxetine increased only swimming behavior. The combination of
      fluoxetine with desipramine or bupropion increased both climbing and swimming
      behaviors at certain doses, but higher doses of desipramine when combined with
      fluoxetine replaced swimming behavior with climbing behavior. The mixed NE-5-HT
      reuptake inhibitors milnacipran and duloxetine reduced immobility and increased
      climbing behavior, but did not alter swimming. Venlafaxine reduced immobility and
      increased swimming behavior, except at the highest dose tested (80 mg/kg), which
      increased both swimming and climbing behaviors. Thus, combining certain doses of
      pharmacologically selective monoamine reuptake inhibitors, or the mixed reuptake
      inhibitor venlafaxine, produced a pattern of mixed active behaviors in the FST
      (climbing and swimming) that may reflect the activity of multiple
      neurotransmitters, especially the combination of enhanced 5-HT and DA activity.
      The combination of higher doses of desipramine with fluoxetine, or compounds with
      mixed activity at inhibiting NE and 5-HT reuptake, demonstrated effects similar
      to those of desipramine alone and may reflect inhibition of the expression of
      serotonergic antidepressant behavioral effects by selective NE reuptake
      inhibitors.

PMID- 9551777
TI  - Lack of effect of hydrocortisone treatment on d-fenfluramine-mediated prolactin
      release.
AB  - The prolactin responses to the serotonin (5-HT) releasing agent d-fenfluramine
      (30 mg orally) were studied in 11 male normal volunteers after administration of
      hydrocortisone (20 mg orally, twice daily for 10 days) using a double-blind,
      placebo-controlled, cross-over design. While hydrocortisone treatment
      significantly elevated 24-h urinary cortisol excretion, it did not lower the
      prolactin response to d-fenfluramine. Plasma levels of d-fenfluramine and d
      norfenfluramine were not altered by hydrocortisone treatment. These findings show
      that following 10 days administration of hydrocortisone, the prolactin responses
      to d-fenfluramine are not changed.

PMID- 9551778
TI  - Double-blind placebo controlled trial of dextrose tablets and nicotine patch in
      smoking cessation.
AB  - In a placebo-controlled double-blind trial 308 smokers were individually randomly
      allocated to one of four groups: 1) 3 g dextrose tablets and 15 mg nicotine
      transdermal patch; 2) dextrose and placebo patch; 3) placebo tablets and nicotine
      patch; 4) placebo tablets and placebo patch. Patients were scheduled to attend
      weekly smokers clinic sessions starting 1 week before the quit date and continue
      for 4 weeks after that date. The primary outcome variable was biochemically
      verified abstinence at the final session, four weeks after the scheduled quit
      date. The proportion of smokers abstinent in the four groups was as follows: 49% 
      dextrose plus active patch; 44% - dextrose plus placebo patch; 36% - placebo
      tablet plus active patch; 30% - placebo tablet plus placebo patch. The difference
      between the dextrose and placebo tablets (13%) was statistically significant (P <
      0.01, one-tailed); the difference between the active and placebo patches (6%) was
      not. There was no significant difference between the effect of the dextrose when
      accompanied by active versus placebo patches. There was no significant effect of
      dextrose on weight. The results suggest that dextrose supplementation to the diet
      may be a cheap and simple aid to giving up smoking. Further research is now
      needed to establish its long-term efficacy.

PMID- 9551779
TI  - Synergistic effect of status epilepticus and ischemic brain injury on mortality.
AB  - Ischemic brain injury (stroke) is a major cause of status epilepticus (SE). In
      our database of 529 adult SE cases, acute or remote cerebrovascular accidents
      (CVA) were a primary cause of SE for 41% of the patients overall and for 61% of
      the elderly patients. SE in the setting of acute CVA has a very high mortality,
      approaching 35%. The degree to which mortality can be attributed to the severity
      of the underlying CVA etiology vs. the effect of SE has not been evaluated. To
      address this issue, we prospectively studied patients with SE and acute CVA and
      compared them to control populations with acute CVA alone or with SE and remote
      CVA. The groups did not significantly differ with regard to age, sex, or
      radiographic lesion size. Mortality was unrelated to lesion size in the CVA and
      SE group. Overall, acute CVA and SE patients had an almost three-fold increase in
      mortality compared to the CVA group and an eight-fold increase compared to the SE
      and the non acute (remote) CVA group. Logistic regression analysis demonstrated a
      statistically significant synergistic effect of SE and CVA on mortality. This is
      the first study to document that the high mortality of SE and acute CVA is not
      solely due to the severity of the underlying CVA etiology, but due to the
      synergistic effect of combined injuries from SE and cerebral vascular ischemia.

PMID- 9551780
TI  - Multivariable prediction of seizure outcome one year after resective epilepsy
      surgery: development of a model with independent validation.
AB  - PURPOSE: To identify predictors of seizure-outcome after epilepsy surgery and
      validate the findings in an independent series of patients. To use the results to
      develop a predictive model. METHODS: Sequential patients undergoing resective
      surgery for medically intractable epilepsy were identified at Yale New Haven
      Hospital (1987-1990, group 1) and Columbia Presbyterian Hospital (1991-1994,
      group 2). Information about seizure outcome and predictors of outcome was
      obtained from medical chart review. Good seizure-outcome was defined as having
      been seizure-free for one year beginning with discharge from the hospital.
      Multiple logistic regression was used to develop a model of predictors in group
      1. It was then validated in group 2. RESULTS: There were 133 patients in group 1
      and 81 in group 2. In a multivariable analysis, independent predictors of outcome
      in group 1 were presence of mesial temporal sclerosis based on postsurgical
      pathological analysis (MTS) (relative risk (RR) = 1.47), having a known
      underlying etiology (RR = 1.32), and partial seizures only (RR = 1.17). In group
      2, the findings for each factor were similar to those in group 1: MTS, RR = 1.49;
      etiology, RR = 1.32; and partial seizures, RR = 1.24. Used in combination, these
      three factors can identify patients with nearly a 100% chance of being seizure
      free (all three factors present) versus less than a 50% chance (none of the three
      factors present). CONCLUSIONS: With independent validation of the findings, we
      can be reasonably certain that the three factors identified in this analysis are
      meaningful and generalizable predictors of seizure outcome following epilepsy
      surgery. Use of predictive models should be considered in future studies to
      convert study results into clinically relevant statements about a particular
      patient's likelihood of surgical success.

PMID- 9551781
TI  - Vigabatrin enhances promoted release of GABA in neonatal rat optic nerve.
AB  - Vigabatrin (gamma-vinyl GABA) is an antiepileptic drug and blocks GABA
      transaminase activity resulting in elevations in cellular GABA levels in the
      brain. Nipecotic acid (NPA) promotes release of GABA from neonatal optic nerve
      astrocytes, resulting in a bicuculline-sensitive depolarization of the optic
      nerve axons. The NPA-induced depolarization of vigabatrin-treated rats (100
      mg/kg, i.p.) more than doubled, suggesting an elevation in free GABA levels; the
      GABA transporter inhibitor, NO-711 reduced the depolarization. These results are
      consistent with the known ability of vigabatrin to block the GABA degradation
      enzyme GABA-transaminase, suggesting that vigabatrin elevates astrocytic GABA
      levels, thereby favoring greater release of GABA through the GABA transporter.

PMID- 9551782
TI  - Quality of life in epilepsy: comparison of four preference measures.
AB  - Several specific and general measures are available for the assessment of overall
      health related quality of life in epilepsy. Few of the commonly used measures
      provide utility weights for use in cost-utility analyses. This study compares
      four methods for measuring utility weights: time trade-off (TTO), standard gamble
      (SG), 15D, end the EuroQol visual analog scale. All patients aged 18-67 years
      with a diagnosis of epilepsy, who had been admitted to or attended the outpatient
      clinic at a large county hospital 1987-1994, received a comprehensive
      questionnaire. From 397 respondents, 82 patients were randomly selected. Most of
      the 57 patients completing the study generally had well-controlled epilepsy, but
      were still on anti-epileptic medication. Mean age was 44 years. Fourty-one
      percent were male and 59% female. The resulting utility weights differed
      considerably between the measures, both with regard to central tendency and
      dispersion. Median utility scores: EuroQol visual analog scale 0.75, 15D 0.90,
      TTO 0.98, SG 0.99. There was a good association between the EuroQol rating scale
      and the 15D, and a moderate association between SG and TTO. These preference
      instruments measure different aspects of health-related quality of life and thus
      yield different results. Caution should be taken when interpreting cost-utility
      studies, as results will depend on the choice of utility instrument.

PMID- 9551783
TI  - Attenuation of kindling-induced decreases in NT-3 mRNA by thyroid hormone
      depletion.
AB  - The expression of neurotrophins is altered by amygdala kindled seizures. Because
      thyroid hormone can regulate the transcription of neurotrophins, we asked whether
      thyroid hormone regulates neurotrophin mRNA expression following amygdala
      kindling. Rats with electrodes implanted in the basolateral nucleus of the
      amygdala were either depleted of thyroid hormone or given excess thyroid hormone.
      The rats were then kindled daily until they had one generalized seizure. The
      brains were removed 4 h after the seizure and processed for in situ hybridization
      of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and
      neurotrophin-3 (NT-3) mRNAs. In non-kindled rats, thyroid hormone depletion
      increased the levels of BDNF mRNA in the paraventricular nucleus of the
      hypothalamus and the pituitary gland. NGF and NT-3 mRNA expression was not
      altered. In addition, thyroid hormone manipulations had no effect on kindling or
      on kindling-induced BDNF and NGF mRNA. However, the kindling-induced decrease in
      NT-3 mRNA expression in the dentate gyrus granule cell layer was significantly
      attenuated by thyroid hormone depletion. These effects were reversed by thyroid
      hormone replacement. The results indicate that thyroid hormone plays a modulatory
      role in the seizure-induced changes of NT-3 mRNA expression found in the dentate
      gyrus.

PMID- 9551784
TI  - Electroencephalographic and histological characteristics of a model of limbic
      status epilepticus permitting direct control over seizure duration.
AB  - Status epilepticus is a neurological emergency associated with substantial
      morbidity and mortality. Experimental and clinical investigations suggest that
      prolonged seizure activity is associated with injury to vulnerable neurons.
      Compounds with neuroprotective properties may minimize such injury. Existing
      methods of inducing experimental status epilepticus result in seizure activity of
      variable duration and neuronal injury of variable degree. To minimize such
      variability, status epilepticus may be stopped with anticonvulsants, but this
      limits the ability to screen for independent neuroprotective properties. We have
      developed a simple and reliable non-pharmacological model of limbic status
      epilepticus in which the duration of status epilepticus is under direct
      experimental control. Status epilepticus is induced by continuous, unilateral
      hippocampal stimulation. Using this model, the degree of hippocampal pyramidal
      cell injury varies in direct proportion to status epilepticus duration across a
      range of 15-140 min. A progressive sequence of EEG changes unfolds with
      increasing status epilepticus duration, resembling that seen in other models.
      This model may serve as a reference against which the effects of potential
      neuroprotective compounds can be studied.

PMID- 9551785
TI  - A summary of mechanistic hypotheses of gabapentin pharmacology.
AB  - Although the cellular mechanisms of pharmacological actions of gabapentin
      (Neurontin) remain incompletely described, several hypotheses have been proposed.
      It is possible that different mechanisms account for anticonvulsant,
      antinociceptive, anxiolytic and neuroprotective activity in animal models.
      Gabapentin is an amino acid, with a mechanism that differs from those of other
      anticonvulsant drugs such as phenytoin, carbamazepine or valproate. Radiotracer
      studies with [14C]gabapentin suggest that gabapentin is rapidly accessible to
      brain cell cytosol. Several hypotheses of cellular mechanisms have been proposed
      to explain the pharmacology of gabapentin: 1. Gabapentin crosses several membrane
      barriers in the body via a specific amino acid transporter (system L) and
      competes with leucine, isoleucine, valine and phenylalanine for transport. 2.
      Gabapentin increases the concentration and probably the rate of synthesis of GABA
      in brain, which may enhance non-vesicular GABA release during seizures. 3.
      Gabapentin binds with high affinity to a novel binding site in brain tissues that
      is associated with an auxiliary subunit of voltage-sensitive Ca2+ channels.
      Recent electrophysiology results suggest that gabapentin may modulate certain
      types of Ca2+ current. 4. Gabapentin reduces the release of several monoamine
      neurotransmitters. 5. Electrophysiology suggests that gabapentin inhibits voltage
      activated Na+ channels, but other results contradict these findings. 6.
      Gabapentin increases serotonin concentrations in human whole blood, which may be
      relevant to neurobehavioral actions. 7. Gabapentin prevents neuronal death in
      several models including those designed to mimic amyotrophic lateral sclerosis
      (ALS). This may occur by inhibition of glutamate synthesis by branched-chain
      amino acid aminotransferase (BCAA-t).

PMID- 9551786
TI  - Comparison of EEG, MRI and PET in reading epilepsy: a case report.
AB  - The pathophysiological and neuroanatomical bases of reading epilepsy (RE) are
      unclear. We performed video-EEG, high quality MRI and [11C]diprenorphine PET in a
      patient with RE to detect structural and functional abnormalities. EEG showed
      multifocal seizure onset bilaterally in temporal and fronto-central regions. MRI
      was normal, whereas [11C]diprenorphine PET revealed peri-ictal opioid binding
      decreases in both temporal lobes and the left frontal lobe. These findings
      confirm that RE is due to abnormal activity in the network subserving reading.

PMID- 9551787
TI  - Proconvulsant effects induced by pyridoxine in young rats.
AB  - High doses of pyridoxine (vitamin B6) can be neurotoxic in adults. Effects of
      intraperitoneally administered B6 (100, 250 and 400 mg/kg) were studied in 7, 12,
      18 and 60 day old rats. B6 elicited epileptiform EEG discharges without any motor
      correlate in all age groups. In contrast, motor seizures were rare, seen only in
      18 day old rats (250 mg/kg of B6). Data indicate that in young rats, B6 may have
      proconvulsant effects in doses relevant to those sometimes used in pediatric
      neurology.

PMID- 9551788
TI  - Affinity capillary electrophoresis: a physical-organic tool for studying
      interactions in biomolecular recognition.
AB  - Affinity capillary electrophoresis (ACE) is a technique that is used to measure
      the binding affinity of receptors to neutral and charged ligands. ACE experiments
      are based on differences in the values of electrophoretic mobility of free and
      bound receptor. Scatchard analysis of the fraction of bound receptor, at
      equilibrium, as a function of the concentration of free ligand yields the
      dissociation constant of the receptor-ligand complex. ACE experiments are most
      conveniently performed on fused silica capillaries using a negatively charged
      receptor (molecular mass < 50 kDa) and increasing concentrations of a low
      molecular weight, charged ligand in the running buffer. ACE experiments that
      involve high molecular weight receptors may require the use of running buffers
      containing zwitterionic additives to prevent the receptors from adsorbing
      appreciably to the wall of the capillary. This review emphasizes ACE experiments
      performed with two model systems: bovine carbonic anhydrase II (BCA II) with
      arylsulfonamide ligands and vancomycin (Van), a glycopeptide antibiotic, with D
      Ala-D-Ala (DADA)-based peptidyl ligands. Dissociation constants determined from
      ACE experiments performed with charged receptors and ligands can often be
      rationalized using electrostatic arguments. The combination of differently
      charged derivatives of proteins - protein charge ladders - and ACE is a physical
      organic tool that is used to investigate electrostatic effects. Variations of ACE
      experiments have been used to estimate the charge of Van and of proteins in
      solution, and to determine the effect of the association of Van to Ac2KDADA on
      the value of pKa of its N-terminal amino group.

PMID- 9551789
TI  - Dynamic complexation of solutes in capillary electrophoresis.
AB  - The analyte migration behavior in any chemical separation system can be described
      using a single equation that unifies all areas of separation science. This
      equation can be used in capillary electrophoresis (CE) to design separation
      systems, and to study interactions between analytes and additives. By using
      individual capacity factors for each analyte species present in the system, and
      with the knowledge of the characteristics of each interaction, one can predict
      the analyte migration behavior in complicated CE systems, including systems with
      multiple 1:1 interactions and/or higher order interactions.

PMID- 9551790
TI  - The effects of a mixture of charged and neutral additives on analyte migration
      behavior in capillary electrophoresis.
AB  - Multicomponent additives, such as derivatized cyclodextrins with various degrees
      of substitution, can be considered single-component additives as long as the
      fraction of each component remains constant. In this paper, equations are derived
      describing the effect of such additives on the migration behavior of analytes.
      These equations are used in the study of capillary electrophoresis (CE) systems
      with differentially charged cyclodextrins as additives. For weakly acidic
      analytes, the binding with highly negatively charged sulfobutyl ether beta
      cyclodextrin (SBE-beta-CD) increases their negative electrophoretic mobility,
      while the binding with neutral hydroxypropyl-beta-cyclodextrin (HP-beta-CD)
      decreases their negative mobility. By obtaining the equilibrium constants and
      mobilities for each additive with each analyte (in this case, phenol, 2-naphthol
      and 1-naphthol), the migration behavior of these analytes in CE systems is
      quantitatively predicted at various concentrations of mixtures of the two
      additives. The properties of the contour lines in the binding isotherm surfaces
      of such CE systems are discussed.

PMID- 9551791
TI  - Capillary affinophoresis of pea lectin with polyliganded affinophores: a model
      study of divalent-polyvalent interactions.
AB  - Affinophoresis is a type of affinity electrophoresis using an affinophore, a
      soluble ionic carrier bearing affinity ligand(s). It was reported previously that
      an affinophore, prepared by coupling multiple p-aminophenyl alpha-D-mannoside
      ligands to a part of the carboxyl groups of succinylated polylysine, specifically
      changed the mobility of pea lectin in agarose gel. The affinophoresis of this
      divalent lectin with the polyliganded affinophore was investigated by using
      capillary electrophoresis. Analysis of the mobility change of the lectin in the
      presence of differently modified affinophores showed that the affinity was larger
      for affinophores having higher ligand density. Analysis of the inhibition of the
      mobility change by a neutral ligand, with a known affinity constant for the
      lectin, allowed estimation of the contributions of monovalent and divalent
      interactions to the binding in the lectin-affinophore complex. The proportion of
      divalent complexes was greater for affinophores having higher ligand density.
      This approach to estimate the contribution of divalency in complex formation
      should be generally applicable to the analysis of divalent interactions with
      different techniques other than electrophoresis.

PMID- 9551792
TI  - On-line competitive immunoassay based on capillary electrophoresis applied to
      monitoring insulin secretion from single islets of Langerhans.
AB  - An automated on-line competitive immunoassay based on capillary electrophoresis
      (CE) was utilized to monitor secretion of insulin from single islets of
      Langerhans stimulated by glucose and tolbutamide. In the instrument, fluorescein
      isothiocyanate-labeled insulin (FITC-insulin), monoclonal anti-insulin and
      perifusate of single islets were mixed on-line while islets were exposed to
      different levels of glucose and tolbutamide. Insulin released from single islets
      competed with FITC-insulin for antibody binding sites. Therefore, the amounts of
      bound and free FITC-insulin were modulated by insulin released from islets. The
      bound and the free FITC-insulin were separated by CE every 3 s and the bound over
      free ratio (B/F) was measured. Insulin levels were obtained by comparing B/F with
      calibration curves obtained under the same conditions except that the islet
      perfusate was replaced with various concentrations of insulin. Patterns of
      insulin secretion stimulated by glucose and tolbutamide observed were comparable
      to what has been seen previously using radioimmunoassay or enzyme-linked
      immunoassay. This on-line competitive immunoassay system provided a fast and
      direct way to measure insulin release from single islets. The effects of
      temperature on antibody-antigen reaction rate and binding equilibrium were also
      studied.

PMID- 9551793
TI  - A diagnostic test for scrapie-infected sheep using a capillary electrophoresis
      immunoassay with fluorescent-labeled peptides.
AB  - Scrapie in sheep and goats is the prototype of transmissible spongiform
      encephalopathies found in humans and animals. A feature of these diseases is the
      accumulation of rod-shaped fibrils in the brain that form from an aggregated
      protein. This protein (PrPSC) is a protease-resistant form of a normal host cell
      protein. When the aggregated protein is denatured in sodium dodecyl sulfate (SDS)
      and beta-mercaptoethanol, a monomer form of approximately 27 kDa molecular mass
      is observed. A competition immunoassay to detect PrPSC from scrapie-infected
      sheep was developed using free zone capillary electrophoresis with laser-induced
      fluorescence (LIF) for detection and flourescein-labeled synthetic peptides from
      PrPSC. Antibodies were made to each respective peptide and used in the
      competition assay. The fluorescent-labeled peptides bound to the antibody were
      separated from the unbound peptides using 200 mM Tricine, pH 8.0, containing 0.1%
      n-octylglucoside and 0.1% bovine serum albumin (BSA). The amount of antibody that
      would bind approximately 50% of the fluorescent-labeled peptide was determined
      for each peptide. When unlabeled peptide was added to the assay, approximately 2
      fmoles of the peptide could be measured. When PrPSC extracted from infected sheep
      brain was added to the assay, approximately 135 pg of PrPSC could be detected.
      When preparations from normal sheep were assayed, there was little or no
      competition for the bound peptides. Assays using two of the peptides, peptides
      spanning amino acid positions 142-154 and 155-178, clearly differentiated scrapie
      positive sheep from normal animals. This assay is a new method that can be used
      to diagnose scrapie and, possibly, other transmissible spongiform
      encephalopathies in animals and in humans.

PMID- 9551794
TI  - Affinity capillary electrophoresis investigation of an epitope on human
      immunodeficiency virus recognized by a monoclonal antibody.
AB  - Affinity capillary electrophoresis (ACE) has been used to investigate the epitope
      on the human immunodeficiency virus (HIV) core protein p24 recognized by the
      monoclonal antibody (mAb) 13-102-100. The affinity of a series of peptides with N
      and C-terminal truncations of the epitope sequence determined by mass
      spectrometry was studied. The peak area change assay was used for the study of
      the interactions of the mAb with those peptides, exhibiting tight binding to the
      mAb, and the migration time shift assay was used to probe the relative affinities
      of peptides showing weak binding to the mAb. The experimental results show that
      the monoclonal antibody 13-102-100 recognizes the peptide VHPVHAGPIAP with
      highest affinity. Smaller peptides incorporating only part of the epitope,
      however, are recognized to some extent in the ACE experiments.

PMID- 9551795
TI  - Double enzyme-catalyzed microreactors using capillary electrophoresis.
AB  - This work evaluates the concept of a double enzyme-catalyzed microreactor using
      capillary electrophoresis (CE). Migrating in a capillary under electrophoresis
      conditions, plugs of substrate and two enzymes are injected separately in buffer
      and allowed to react. Extent of reaction and product ratios were subsequently
      determined by CE. This concept is demonstrated using two model systems: the
      conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and
      adenosine monophosphate (AMP) by hexokinase (HK, EC 2.7.1.1) and apyrase (APY, EC
      3.6.1.5), respectively, in the conversion of glucose to glucose-6-phosphate and
      inorganic phosphate, respectively, and the conversion of nicotinamide adenine
      dinucleotide, reduced form (NADH), to nicotinamide adenine dinucleotide (NAD) and
      back to NADH by lactate dehydrogenase (LDH, EC 1.1.1.27) and glucose-6-phosphate
      dehydrogenase (G6PDH, EC 1.1.1.49), respectively, in the conversion of pyruvate
      to lactate and glucose-6-phosphate (glc-6-P) to 6-phosphogluconate, respectively.
      These procedures illustrate the use of the capillary as a double microreactor and
      the ease of quantitation of reaction products under conditions of
      electrophoresis.

PMID- 9551796
TI  - Affinity mode of capillary isoelectric focusing for the characterization of the
      biotin-binding protein actinavidin.
AB  - Different modes of capillary isoelectric focusing (CIEF) with salt mobilization
      and zwitterionic additive to cathodic mobilizer were applied to characterize the
      biotin-binding protein actinavidin and its affinity properties. The analysis is
      performed in a neutral coated capillary with completely eliminated electroosmotic
      flow. Synthetic pI standards with absorption in the visible region were used in
      all runs and pI determinations were based on a fitted nonlinear calibration
      graph. CIEF of highly purified actinavidin in native conditions was revealed in
      about 12 peaks in pI range 6.2-7.5, with three major forms having pI 6.80, 6.86,
      6.90. CIEF of a mixture of actinavidin and increasing concentrations of two
      affinity ligands (biotin and biotinylated oligonucleotide) demonstrated drastic
      changes in the number of protein isoforms. In the latter case it resulted in only
      one peak (pI 5.05) when the ligand was in excess. This method, which can be named
      affinity CIEF, was found to be well-suited for studying structural changes,
      occurring in receptor proteins upon binding with a ligand. CIEF of the protein,
      performed under denaturing conditions (6 M urea in a solution of carrier
      ampholytes) is also reported. It was revealed in three isoforms with a pI more
      acidic than that of native actinavidin. It is demonstrated that careful selection
      of denaturing conditions was necessary for the reproducible results.

PMID- 9551797
TI  - Base-specific separation of oligodeoxynucleotides by capillary affinity gel
      electrophoresis.
AB  - Capillary affinity gel electrophoresis was applied to sequence-specific and base
      composition-specific recognition of oligodeoxynucleotides, utilizing the
      formation of heteroduplexes between a nucleic acid analogue immobilized into the
      capillary gel and soluble oligodeoxynucleotides with different sequences.
      Capillary affinity gel electrophoresis using capillaries filled with a conjugated
      gel of polyacrylamide and a synthetic nucleic acid analogue [poly(9
      vinyladenine)] was effective for the selective separation of hexathymidylic acid
      from a mixture of four homopolymers of A6, C6, G6, and T6 and for the complete
      resolution of five heteropolymers of hexadeoxynucleotides (TAAAAA, TTAAAA,
      TTTAAA, TTTTAA, TTTTTA). We also demonstrated that capillary affinity gel
      electrophoresis was useful for the selective and the sensitive sequence-specific
      recognition of sequence isomers of DNA (TTTTAA, TTTTAAT, TTTATA, and TTTTAA).

PMID- 9551798
TI  - Affinity capillary electrophoresis employing immobilized glycosaminoglycan to
      resolve heparin-binding peptides.
AB  - A new capillary electrophoresis technique has been developed for the affinity
      resolution of synthetic heparin-binding peptides using an immobilized
      glycosaminoglycan. Heparin and heparan sulfate were immobilized onto fused silica
      capillaries using biotin-neutravidin conjugation. These capillaries exhibited
      markedly reduced electroosmotic flow and were able to distinguish peptides based
      on the heparin binding domain of acidic fibroblast growth factor (residues 125
      144, GLKKNGSCKRGPRTHYGQKA) that differed only in the stereochemistry of the
      proline amino acid residue. The peptide based on the native sequence was retarded
      compared to the peptide having unnatural stereochemistry, consistent with its
      stronger interaction for immobilized glycosaminoglycan. Improved resolution is
      also obtained for additional arginine and lysine containing heparin-binding
      peptides.

PMID- 9551799
TI  - A heparin-binding peptide from human serum amyloid P component characterized by
      affinity capillary electrophoresis.
AB  - Affinity capillary electrophoresis (CE) was used for a detailed characterization
      of the binding between heparin and a peptide isolated from the heparin-binding
      serum protein amyloid P component (SAP). The peptide corresponds to a tryptic
      fragment (T3) comprising amino acids 14-38 of SAP. By including ligands in the
      electrophoresis buffer various glycosaminoglycans could be screened for binding
      of T3 using one sample aliquot. The binding was found to be highly specific for
      heparin and heparin fragments down to tetramers and appeared strongest at a
      slightly alkaline pH while no binding could be demonstrated with heparan sulfate,
      chondroitin sulfate, desulfated heparin, mannose 6-phosphate and phosphotyrosine.
      The T3-heparin complexes were sufficiently stable to perform quantitative
      measurements of the binding using preequilibration of samples prior to a CE
      mediated separation of bound and free T3-peptide. Plots based on quantitation of
      analyte peaks corresponding to free and complexed T3 yielded a dissociation
      constant of 1.5 microM for the interaction with heparin. The results indicate
      that a specific subfraction of the heparin molecules is active in binding
      interactions with the peptide. The affinity CE approach proved to be useful for
      these studies because of its sensitivity to complex formation involving charged
      ligands and the possibility of achieving separations under native conditions.
      Also advantageous is the low sample consumption and the ability to analyze
      unlabeled reactants in solution.

PMID- 9551800
TI  - Using capillary electrophoresis/frontal analysis to screen drugs interacting with
      human serum proteins.
AB  - We have used capillary electrophoresis in the frontal analysis mode (CE/FA) to
      determine the binding capacity of beta-adrenoceptor blocking drugs to individual
      serum proteins, serum protein mixtures and human serum. The free drug
      concentration was directly measured from the height of the frontal peak and used
      to calculate the bound drug concentration. From the bound drug concentration, the
      percentage of drug bound to the serum proteins alpha1-acid glycoprotein (AGP) and
      human serum albumin (HSA) was then determined. In addition to determining the
      percent of a drug bound to a protein, the drug-protein association constant (Ka)
      was determined for AGP binding to beta-blockers. The data-estimated association
      constants were consistent with literature values. The CE/FA studies on the beta
      adrenoceptor blocking drugs and the serum proteins indicated that HSA, AGP, high
      density lipoprotein (HDL), and low density lipoprotein (LDL) were the main
      contributors to serum binding for this series of compounds. The serum-drug
      binding data sorted the beta-adrenoceptor blocking drugs into high and low
      binding categories. The protein mixture (AGP + HSA + HDL + LDL) resulted in
      dividing the beta-blockers into the same high/low rankings. The protein mixture
      (AGP + HSA + HDL + LDL) was amenable to automation, did not autoaggregate, and
      had constant concentrations for the proteins.

PMID- 9551801
TI  - Separation of the enantiomers of ibuprofen and its major phase I metabolites in
      urine using capillary electrophoresis.
AB  - A capillary electrophoresis method for determination of the enantiomers of
      ibuprofen and its major phase I metabolites: 2'-hydroxyibuprofen and 2'
      carboxyibuprofen in urine samples have been developed. Cyclodextrins and linear
      dextrins have been investigated as chiral selectors. Simultaneous chiral
      separation of the enantiomers of ibuprofen, 2'-hydroxyibuprofen and 2'
      carboxyibuprofen was obtained using a mixture of dextrin 10 and heptakis (2,3,6
      tri-O-methyl)-beta-cyclodextrin in a 2-[N-morpholino]ethanesulphonic acid buffer,
      pH 5.26. The electroosmotic flow was reversed using hexadimethrine bromide as a
      buffer additive. The method can be used for the determination of the free
      enantiomers of ibuprofen, 2'-hydroxyibuprofen and 2'-carboxyibuprofen as well as
      for the indirect determination of their glucuronic acid conjugates in urine
      samples.

PMID- 9551802
TI  - Exploitation of a monoclonal antibody for weak affinity-based separation in
      capillary gel electrophoresis.
AB  - Weak biospecific recognition has been established for affinity separation in high
      performance liquid chromatography (HPLC). The use of weak affinity chromatography
      (WAC) has been limited previously by the insufficient separation efficiency
      achieved, allowing only some 1000 plates/m to be obtained. However, it has been
      shown that chiral drug separation can be performed with capillary affinity gel
      electrophoresis (CAGE) at considerably improved efficiency as compared with
      traditional chromatographic procedures. Our present study demonstrates the
      potential of weak affinity monoclonal antibodies as a generic method for
      immunologically based separations in capillary electrophoresis. Monoclonal
      antibodies were polymerized within a silica capillary and were used for the
      separation of structurally similar carbohydrate antigens. The results indicate
      that weak biospecific interactions can be utilized in a CAGE format to produce
      highly selective separation of the alpha- and beta-forms of p-nitrophenyl-labeled
      maltose. It remains to be seen, however, how efficient weak affinity separation
      in CAGE can be compared with affinity HPLC protocols. Details of typical
      separations and of the preparation of the antibody gel are presented.

PMID- 9551803
TI  - Determination of rat liver triglycerides by gas-liquid chromatography and
      reversed-phase high-performance liquid chromatography.
AB  - Rats fed with a fat-free or an olive oil-rich diet were employed to compare the
      response of two chromatographic techniques in the determination of rat liver
      triglyceride (TG) molecular species composition. Gas-liquid chromatography (GLC)
      on polarizable liquid phase and reversed-phase high-performance liquid
      chromatography (RP-HPLC) have been commonly employed for TG analysis, obtaining a
      similar number of chromatographic peaks when used for animal tissue TG
      determination. In the present study similar results were achieved with regard to
      most relevant chromatographic peaks, however, important differences were found in
      the content of minor TGs. Indeed, RP-HPLC permitted separation of long chain
      polyunsaturated fatty acids, which were not detected by GLC, while the latter
      technique reported a higher number of myristoyl-containing TG species. RP-HPLC
      analysis reported a greater number of TGs, with more similarity to a random
      composition, made up from the liver fatty acid composition. Therefore, it was
      concluded that utilization of both techniques would be helpful for liver TG
      analysis as the use of only one of them does not provide a complete profile of
      liver TGs. Nevertheless RP-HPLC seems to be more useful for this purpose since
      revealed a more extensive profile.

PMID- 9551804
TI  - Simultaneous determination of tetrahydrocortisol and tetrahydrocortisone in human
      plasma and urine by stable isotope dilution mass spectrometry.
AB  - A capillary gas chromatographic-mass spectrometric method for the simultaneous
      determination of tetrahydrocortisol (THF, 3alpha,11beta,17alpha,21-tetrahydroxy
      5beta-preg nane-20-one), allo-tetrahydrocortisol (allo-THF,
      3alpha,11beta,17alpha,21-tetrahydroxy-5alpha-pre gnane-20-one) and
      tetrahydrocortisone (THE, 3alpha,17alpha,21-trihydroxy-5beta-pregnane-11,20-dion
      e) in human plasma and urine is described. [1,2,3,4,5-2H5]THF (THF-d5), allo
      [1,2,3,4,5-2H5]THF (allo-THF-d5) and [1,2,3,4,5-2H5]THE (THE-d5) were used as
      internal standards. A double derivatization
      (bismethylenedioxypentafluoropropionate, BMD-PFP) made possible the separation of
      the three tetrahydrocorticoids with good gas chromatographic behavior.
      Quantitation was carried out by selected-ion monitoring of the characteristic
      fragment ions ([M-30]+) of the BMD-PFP derivatives of THF, allo-THF and THE. The
      sensitivity, specificity, precision and accuracy of the method were demonstrated
      to be satisfactory for measuring low concentrations of THF, allo-THF and THE in
      human plasma and urine.

PMID- 9551805
TI  - Simultaneous determination of glucocorticoids in plasma or urine by high
      performance liquid chromatography with precolumn fluorimetric derivatization by 9
      anthroyl nitrile.
AB  - A new method for simultaneous determination of glucocorticoids (GCs) in plasma or
      urine by high-performance liquid chromatography (HPLC) with fluorimetric
      detection has been developed. Following extraction with ethyl acetate using a
      reversed-phase disposable cartridge, the six GCs [cortisol (F), cortisone (E),
      prednisolone (PL), prednisone (PN), 6beta-hydroxycortisol (6beta-OHF) and 6beta
      hydroxyprednisolone (6beta-OHP)] and an internal standard (6beta
      hydroxycotortisone) were derivatized by treatment with 9-anthroyl nitrile (9-AN)
      in a mixture of basic catalysts (triethylamine and quinuclidine) to give the
      fluorescent esters through the 21-hydroxyl group. The GC derivatives so obtained
      were then cleaned by a straight-phase disposable cartridge and chromatographed on
      a straight-phase column with an isocratic HPLC technique. The fluorescence
      derivatives of the GCs, including the internal standard, were separated as clear
      single peaks and no interfering peaks were observed on the chromatograms. The
      lower limits of detection for F, E, PL and PN in plasma or urine were 0.1 ng/ml
      and those for 6beta-OHF and 6beta-OHP in plasma or urine were 0.5 ng/ml, at a
      signal-to-noise ratio of 3. The analytical recovery of known amounts of the GCs
      added to plasma or urine were almost 100%. This method can be applied to the
      determination of plasma or urinary F in renal transplant patients who received PL
      and can be applied for other metabolic investigations in relation to the change
      in blood pressure via 11beta-hydroxysteroid dehydrogenase or in hepatic
      metabolizing via CYP3A4.

PMID- 9551806
TI  - Ethyl acetate extraction procedure and isocratic high-performance liquid
      chromatographic assay for testosterone metabolites in cell microsomes.
AB  - An isocratic reversed-phase high-performance liquid chromatography (HPLC) method
      was developed and validated for separation of testosterone and its main
      metabolites over the nominal range 20 to 40 microg/ml and 280 to 4600 ng/ml,
      respectively. Mobile phase composition (phosphate buffer-methanol-acetonitrile,
      50:38.5:11.5) was optimised by studying the influence of numerous chromatographic
      parameters. The most critical one was the ratio CH3CN/CH3OH. Good recoveries
      (around 90% for all compounds) and an improved specificity were assessed by a
      double ethyl acetate extraction of biological samples. According to the
      performance criteria tested, the method could be applied to enzymatic inhibition
      and induction in vitro studies.

PMID- 9551807
TI  - Study of factors affecting the determination of total plasma 7-fluorobenzo-2-oxa
      1,3-diazole-4-sulfonate (SBD)-thiol derivatives by liquid chromatography.
AB  - A detailed investigation of the factors affecting the determination of total
      plasma 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD)-thiol derivatives (i.e.
      cysteine, homocysteine and cysteinylglycine) is described. Essentially, this
      assay entails extracting specific thiols by plasma disulphide bond reduction,
      protein precipitation, sulphydryl compound derivatization with the thiol-specific
      fluorogenic reagent ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate (SBD
      F), and subsequent separation with isocratic reversed-phase high-performance
      liquid chromatography. By improving the reliability of several analytical
      parameters (composition of the mobile phase, pretreatment of the sample using
      different reducing and protein precipitation agents, and optimization of the
      derivatization of thiols with SBD-F), a number of critical issues can be
      identified and solved.

PMID- 9551808
TI  - Mimetic ligand-based affinity purification of immune complexes and
      immunoconjugates.
AB  - We developed a simple purification method to purify alkaline phosphatase/anti
      alkaline phosphatase IgG as immune complexes using mimetic affinity
      chromatography wherein the antibody was either a monospecific antibody, a
      bispecific antibody or a commercial polyclonal IgG conjugated with alkaline
      phosphatase (AP-IgG) covalently. The immune complexes or conjugates were
      efficiently bound on the mimetic Blue A6XL column and eluted under mild
      conditions (5-20 mM phosphate buffer). A similar strategy of purifying
      peroxidase/anti-peroxidase antibody complexes was also successfully demonstrated
      using the mimetic Red 3 column. Mimetic affinity chromatography thus appears to
      be a simple method to purify the desired monospecific or bispecific antibodies
      from the respective hybridomas and quadromas.

PMID- 9551809
TI  - Quantitative analysis of polychlorinated biphenyls, organochlorine insecticides,
      polycyclic aromatic hydrocarbons, polychlorinated hydrocarbons and
      polynitrohydrocarbons in spiked samples of soil, water and plasma by selected-ion
      monitoring gas chromatography-mass spectrometry.
AB  - A broad range of pollutants such as polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated hydrocarbons (PCHs), polynitrohydrocarbons (PNHs),
      polychlorinated biphenyls (PCBs) and organochlorine (OCs) insecticides were
      simultaneously analyzed in spiked soil, water or plasma samples by using gas
      chromatography-mass spectrometry (GC-MS). Water and plasma samples containing the
      pollutants were extracted by a solid-phase extraction (SPE) method using florisil
      columns. The soil samples, fortified with the toxicants, were extracted with
      water, methanol or dichloromethane (DCM). The water extract was processed by the
      SPE method. The methanol and DCM samples were dried, dissolved in acetonitrile
      and subjected to the SPE extraction. The extracted samples were analyzed by GC-MS
      programmed to monitor selected ions. The deuterium labelled compounds were used
      as the internal standards. The chromatographic profile of total ions indicated
      complete separation of some compounds such as isophorone, naphthalene, all PCBs,
      most OC insecticides and PNHs; high Mr PAHs and some PCHs were partially or
      incompletely separated. The chromatographic profile of individual ion indicated
      good separation of each ion. The minimum detection limit ranged from 1 to 4 pg
      injected when 1 or 2 ions were monitored or from 20 to 200 pg injected when 20
      ions were monitored. The SPE method that provided 60-105% recovery of pollutants
      from water samples, provided only 2-60% recovery from plasma samples. This may be
      due to the binding of pollutants to plasma proteins. Water recovered 1-30%, while
      methanol or DCM recovered 65-100% of the pollutants added to the soil samples.
      The use of internal standards corrected for the loss of pollutants from plasma or
      soil.

PMID- 9551810
TI  - Short column gas chromatography-mass spectrometry and principal component
      analysis for the identification of coeluted substances in doping control
      analysis.
AB  - The identification of four doping control substances in an artificial mixture,
      using short column gas chromatography-mass spectrometry (GC-MS) analysis was
      examined. Two chromatographic peaks were recorded in the chromatogram, using a
      short capillary column (1.8 m) at an oven temperature of 180 degrees C. The first
      peak was associated with a mixture of a solvent derivative and an artifact. The
      second one corresponded to the mixture of four control substances. Principal
      component analysis was applied on a selected GC-MS data set of the latter peak to
      determine clear full spectra of pure substances from mixture spectra. The time of
      GC-MS analysis was significantly reduced to less than 1 min from 30 min which is
      a typical GC-MS analysis time, using standard methods of doping control analysis.

PMID- 9551811
TI  - Automated preparation and analysis of barbiturates in human urine using the
      combined system of PrepStation and gas chromatography-mass spectrometry.
AB  - A system for an automatic sample preparation procedure followed by on-line
      injection of the sample extract into a gas chromatography-mass spectrometry (GC
      MS) system was developed for the simultaneous analysis of seven barbiturates in
      human urine. Sample clean-up was performed by a solid-phase extraction (SPE) on a
      C18 disposable cartridge. A SPE cartridge was preconditioned with methanol and
      0.1 M phosphate buffer. After loading a 1.5 ml volume of a urine sample into the
      SPE cartridge, the cartridge was washed with 2.5 ml of methanol-water (1:9, v/v).
      Barbiturates were eluted with 1.0 ml of chloroform-isopropanol (3:1, v/v) from
      the cartridge. The eluate (1 microl) was injected into a GC-MS system. The
      calibration curves, using an internal standard method, demonstrated a good
      linearity throughout the concentration range from 0.02 to 10 microg/ml for all
      barbiturates extracted. The proposed method was applied to several clinical
      cases. The total analysis time for 20 samples was approximately 14 h.

PMID- 9551812
TI  - Determination of 22-oxacalcitriol, a new analog of 1alpha,25-dihydroxyvitamin D3,
      in human serum by liquid chromatography-mass spectrometry.
AB  - A sensitive and specific liquid chromatographic-mass spectrometric assay has been
      developed for the determination of 22-oxacalcitriol (OCT), which is a new analog
      of 1alpha,25-dihydroxyvitamin D3. The analyte was isolated from serum by two
      solid-phase extraction steps on a C18 cartridge and NH2 cartridge. The recovery
      of OCT through two extraction steps was more than 90%. A related substance (ED
      94), i.e. OCT with the side-chain shortened by one carbon, was used as an
      internal standard. Extracts were chromatographed on a C18 reversed-phase column
      interfaced to the electrospray ionization source. The mass spectrometer was
      operated in the positive-ion mode of selected reaction monitoring. The
      chromatographic run-time for one injection was less than 6 min. The intra- and
      inter-assay coefficients of variation for the lowest concentration examined (30
      pg ml[-1]) were 9.83 and 10.67, respectively. And the analytical recovery of OCT
      added to serum was quantitative. Assay linearity was obtained in the range of 20
      640 pg ml(-1).

PMID- 9551813
TI  - Determination of sulfonamide antibiotics by gas chromatography coupled with
      atomic emission detection.
AB  - The paper describes the analysis of nine sulfonamides, chosen as the most widely
      used representatives of an important class of antibacterial drugs. Atomic
      emission detection has been found to allow simultaneous quantification and
      identification of the N1-methylated derivatives, which are resolved efficiently
      by conventional capillary gas chromatography. Results are given concerning the
      linearity of the response and the characterization of the individual compounds by
      the elemental ratio of their carbon, nitrogen and sulfur content. The method
      looks promising for the quantitative analysis and confirmation of sulfonamide
      residues in complex mixtures.

PMID- 9551814
TI  - Reversed-phase ion-pair chromatographic analysis of tetracycline antibiotics.
      Application to discolored teeth.
AB  - A high-performance liquid chromatographic method with diode array detection was
      developed to simultaneously separate tetracycline antibiotics and applied to the
      analysis of discolored teeth. By a reversed-phase ion-pair chromatographic system
      using pentanesulfonate as a counter ion, minocycline, oxytetracycline,
      tetracycline and demeclocycline were eluted in this order, and they showed base
      line separation within 9 min. When using oxytetracycline as an internal standard,
      the quantitative ranges were between 2.5 ng/ml and 7.5 microg/ml. Powdered
      dentine (10 mg) and enamel (40 mg) prepared from discolored primary teeth were
      sonicated in 0.25 ml of 10 mM HCl containing oxytetracycline (0.75 microg/ml) and
      50 mM EDTA-2Na, thereafter the supernatants were chromatographed. Eluates from
      both discolored tooth samples were identified as minocycline based on diode array
      spectra of their peaks, while minocycline was not detected in any samples from
      nondiscolored normal teeth, indicating that discoloration of the tested teeth was
      due to minocycline incorporated into dentine and enamel. Replicate quantitative
      analyses of the identical tooth substances showed that intra- and inter-assay
      C.V.s were 2.63 and 4.95% for dentine, and 5.42 and 10.88% for enamel.
      Application of the developed method to nine discolored teeth revealed that the
      incorporated minocycline ranged from 20.13 to 84.62 ng/mg of dentine and 0.89 to
      7.87 ng/mg of enamel.

PMID- 9551815
TI  - Quantitative analytical methods for the determination of a new hypertension drug,
      CGS 25462, and its metabolites (CGS 25659 and CGS 24592) in human plasma by high
      performance liquid chromatography.
AB  - Two simple and sensitive reversed-phase high-performance liquid chromatography
      (HPLC) methods were developed and validated for the quantitative determination of
      a novel hypertension drug CGS 25462 and its major metabolites CGS 24592 and CGS
      25659 in human plasma. CGS 25462 and CGS 25798 (internal standard) were purified
      by one-step liquid-liquid extraction with methylene chloride. The metabolites
      were analyzed on HPLC after plasma protein precipitation with 10% trichloroacetic
      acid (TCA). Separations were achieved on a Zorbax RX C18 column. All compounds
      were detected by using a fluorescence detector. The excitation wavelength was 254
      nm, and emission was monitored at 325+/-12.5 nm. Assessment of recovery and
      reproducibility indicated good accuracy and precision. Over the validation
      concentration range of 10 to 1000 ng/ml for CGS 25462 and 25 to 5000 ng/ml for
      both metabolites, overall mean relative recoveries were 96% for CGS 25462, 101%
      for CGS 25659 and 107% for CGS 24592, and the coefficients of variation were 4.6
      to 13% for CGS 25462, 9.5 to 13% for CGS 25659 and 7.7 to 15% for CGS 24592. The
      limits of quantification (LOQs) were 10 ng/ml for CGS 25462 and 25 ng/ml for CGS
      24592 and CGS 25659, which were of sufficient sensitivity to measure the
      concentrations of CGS 25462, CGS 25659 and CGS 24592 in plasma samples from
      normal volunteers following a single 800 mg oral dose.

PMID- 9551816
TI  - High-performance liquid chromatographic determination of modafinil and its two
      metabolites in human plasma using solid-phase extraction.
AB  - A simple procedure for the simultaneous determination of modafinil, its acid and
      sulfone metabolites in plasma is described. The assay involved an extraction of
      the drug, metabolites and internal standard from plasma with a solid-phase
      extraction using C18 cartridges. These compounds were eluted by methanol. The
      extract was evaporated to dryness at 40 degrees C under a gentle stream of
      nitrogen. The residue was redissolved in 250 microl of mobile-phase and a 30
      microl aliquot was injected via an automatic sampler into the liquid
      chromatograph and eluted with the mobile-phase (26%, v/v acetonitrile in 0.05 M
      orthophosphoric acid buffer adjusted to pH 2.6) at a flow-rate of 1.1 ml/min on a
      C8 Symmetry cartridge column (5 microm, 150 mm x 3.9 mm, Waters) at 25 degrees C.
      The eluate was detected at 225 nm. Intra-day coefficients of variation ranged
      from 1.0 to 2.9% and inter-day coefficients from 0.9 to 6.1%. The limits of
      detection and quantitation of the assay were 0.01 microg/ml and 0.10 microg/ml
      respectively.

PMID- 9551817
TI  - Determination of propofol in low-volume samples by high-performance liquid
      chromatography with fluorescence detection.
AB  - In order to determine propofol in rat whole-blood samples of 50 microl, we
      developed a rapid, simple and reliable method which is characterized by
      precipitation of blood elements with acetonitrile and submission of the
      supernatant to HPLC analysis with fluorescence detection. The method described is
      linear from 0.4 to 40 mg/l and the relative standard deviations in this
      concentration range are less than 10%. The limit of quantification proved to be
      0.4 mg/l. Blood constituents do not interfere with the assay.

PMID- 9551818
TI  - Development and validation of a sensitive method for the determination of
      ganciclovir in human plasma samples by reversed-phase high-performance liquid
      chromatography.
AB  - A rapid, sensitive, specific liquid chromatographic method has been developed for
      the determination of therapeutic levels of ganciclovir in human plasma. Plasma (1
      ml) and acyclovir (I.S.) were treated with 50% trichloroacetic acid. The
      supernatant was neutralized with 2 M NaOH and purified with chloroform. The
      aqueous phase (80 microl) was analyzed by a 3-microm Hypersil ODS C18 column with
      0.04 M triethylamine-0.1 M sodium dihydrogen phosphate monohydrate as the mobile
      phase (1 ml/min) and ultraviolet detection at 254 nm. Calibration was linear from
      50 to 10000 ng/ml. Intra- and inter-day C.V. did no exceed 6.65%. The detection
      limit was about 10 ng/ml.

PMID- 9551819
TI  - Quantification of pyrazinamide and its metabolites in plasma by ionic-pair high
      performance liquid chromatography. Implications for the separation mechanism.
AB  - Pyrazinamide, the amide of pyrazinoic acid, is one of the basic therapeutic
      agents currently used in combination for chemotherapy of tuberculosis. A reversed
      phase high-performance liquid chromatography method based on ionic pair
      chromatography, was developed after solid-phase extraction of the analytes from
      plasma with prior addition of internal standard. The main metabolites, pyrazinoic
      acid, 5-hydroxypyrazinoic acid and 5-hydroxypyrazinamide, were included as well
      as uric acid and other purine derivatives to allow detailed study of the
      pharmacokinetics of the drug, especially in patients with impaired kidney
      function. Some interesting features of the chromatographic system giving some
      insight in the retention mechanism and of the solid-phase extraction are
      discussed in detail.

PMID- 9551820
TI  - Determination of salicylic acid in human serum with capillary zone
      electrophoresis.
AB  - The determination of salicylic acid (SA), a metabolite of aspirin, in human serum
      was developed using capillary zone electrophoresis (CZE) with diode array
      detection. The reproducibility of separation and quantification with CZE analysis
      of the extract of SA from human serum was appropriate for the intra- and inter
      day assay coefficients. A high correlation was revealed between the serum SA
      levels in volunteers determined by CZE and those determined by a fluorescence
      polarization immunoassay (r=0.973, n = 12), although the former values were
      slightly higher than the latter. There were no peaks interfering with the assay
      of SA by internal standard method. This CZE method could provide a simple and
      efficient method for monitoring SA in patients.

PMID- 9551821
TI  - Capillary gas chromatographic analysis of serum bile acids as the n-butyl ester
      trimethylsilyl ether derivatives.
AB  - Gas chromatographic separations of n-butyl ester-trimethylsilyl ether derivatives
      of several common bile acids were compared with those of the corresponding methyl
      ester-trimethylsilyl ether derivatives on a CP-Sil-5 CB capillary column. Both
      types of derivatives were similarly resolved from each other. However, the n
      butyl ester-trimethylsilyl ether derivatives of the bile acids showed longer
      retention times than the corresponding methyl ester-trimethylsilyl ethers and
      unlike the methyl ester-trimethylsilyl ether derivatives, were completely
      resolved from and eluted later than the trimethylsilyl ethers of common plasma
      sterols including sitosterol. A simplified method of plasma work-up for
      quantitation of bile acids and application of the above method in quantification
      of plasma bile acids in humans is described.

PMID- 9551822
TI  - Determination of allantoin in bovine milk by high-performance liquid
      chromatography.
AB  - Determination of allantoin in bovine milk based on high-performance liquid
      chromatography (HPLC) is described. Following dilution and filtration, milk
      samples were analysed directly. Separation and quantification of allantoin was
      achieved using a Spherisorb 5 NH2 column (250 x 4.6 mm ID), acetonitrile-water
      (90:10, v/v) mobile phase at a flow-rate of 2.0 ml min(-1), temperature 20
      degrees C and monitoring the effluent at 214 nm. Total analysis time was 10 min.
      Recovery of allantoin added to milk was 97 (+/-3.7, n = 30)%. Lowest detectable
      concentration was 1 micromol l(-1). Within-day and between-day variability were
      less than 3%. Advantages of improved retention and separation of allantoin, and
      less complicated sample preparation exist over current methods.

PMID- 9551823
TI  - Measurement of serum nitrite/nitrate concentrations using high-performance liquid
      chromatography.
AB  - Previous studies have reported increased serum concentrations of nitrite/nitrate 
      the degradation products of nitric oxide - in Plasmodium vivax malaria and
      uncomplicated Plasmodium falciparum malaria. In all these studies, however,
      nitrite/nitrate has been measured spectrometrically using Griess reagent which
      carries major disadvantages in the determination of serum nitrite/nitrate. The
      method does not allow an exact differentiation of nitrite and biogenic amines
      that are physiologically present in plasma. In the present study we introduce
      high-performance liquid chromatography as a new, accurate and cost effective
      method for determination of serum nitrite/nitrate levels. Significantly increased
      nitrate concentrations were found in malaria patients and serum values remained
      above normal levels for at least 21 days. It could be shown that our HPLC method
      is a sensitive and cost-effective method for direct determination of
      nitrite/nitrate in serum samples, which is not influenced by the presence of
      biogenic amines.

PMID- 9551824
TI  - Simultaneous determination of benzene, toluene, ethylbenzene, and xylenes in
      urine by thermal desorption-gas chromatography.
AB  - The determination of metabolites of benzene, toluene, ethylbenzene, and xylenes
      in urine has been used to assess human exposure to these compounds. The analyses
      of urine samples for these metabolites are tedious and time consuming. The
      determination of unmetabolized individual compounds in urine has been studied
      previously with some success. A simultaneous determination of several
      unmetabolized VOC compounds in urine by thermal desorption-gas chromatography was
      conducted to assess the exposure of smokers and nonsmokers to these compounds.
      The method of thermal desorption-GC was sensitive enough to detect a significant
      difference in exposure levels due to the contribution of light smoking in the
      environmentally-exposed group.

PMID- 9551825
TI  - Analysis of minocycline by high-performance liquid chromatography in tissue and
      serum.
AB  - A sensitive and rapid reversed-phase high-performance liquid chromatography assay
      can be used to accurately determine serum and tissue minocycline concentrations.
      Minocycline is a broad spectrum tetracycline derivative with many applications.
      Tissue and serum samples were obtained from guinea pigs that had received either
      topical or intravenous minocycline. Samples were extracted using a Sep-Pak C18
      cartridge and were injected into a microBondapak C18 column with an isocratic
      methanol mobile phase. Samples were analyzed using UV detection and produced
      sharp peaks with a retention time of 2.5 min. The lower limit of detection was
      100 ng and drug recovery was 61%. This method greatly facilitated the analysis of
      minocycline while allowing for sensitivity.

PMID- 9551826
TI  - High-performance thin-layer chromatographic determination of diltiazem
      hydrochloride as bulk drug and in pharmaceutical preparations.
AB  - A simple, rapid, selective and precise high-performance thin-layer
      chromatographic method for the analysis of diltiazem hydrochloride both as a bulk
      drug and in pharmaceuticals is reported. The mobile phase composition was ethyl
      acetate-methanol-strong ammonia solution (80:10:10, v/v). Densitometric analysis
      of diltiazem hydrochloride was carried out at 238 nm. The calibration curve of
      diltiazem hydrochloride in distilled water was linear in the range 40-400 ng. The
      mean value of correlation coefficient, slope and intercept were 0.997+/-0.0008,
      0.0617+/-0.0012 and 7.16+/-0.2562, respectively. The limits of detection and
      quantitation were 20 ng and 40 ng, respectively. The recovery of diltiazem
      hydrochloride was about 99.5%. The method was utilized to analyse diltiazem
      hydrochloride from conventional and sustained release tablets in the presence of
      commonly used excipients.

PMID- 9551827
TI  - Integration of somatic and visceral inputs by the brainstem: functional
      considerations.
AB  - Studies of the brainstem have traditionally either focused on mechanisms for the
      control of limb or axial muscles or for the maintenance of homeostasis (e.g., the
      circuitry for the regulation of respiration or blood pressure). However, recent
      studies have demonstrated that movement and changes in cardiorespiratory activity
      often are coordinated, indicating a linkage between the pathways that control
      somatic motor activity and those that regulate respiration or circulation.
      Neurons in regions such as nucleus tractus solitarius and the lateral medullary
      reticular formation that regulate circulation and respiration have been shown to
      receive somatic sensory signals (including those from the vestibular system)
      indicating body position in space. In addition, somatic motor control may be
      influenced by signals from visceral receptors that provide cues regarding body
      position in space. Some areas of the brainstem may also participate directly in
      both motor control and regulation of blood pressure and respiration. Thus, a
      simple division of the brainstem into "somatic" and "autonomic" regions is no
      longer possible.

PMID- 9551828
TI  - Force sharing among fingers as a model of the redundancy problem.
AB  - The aim of this study was to test Bernstein's idea that motor synergies provide
      solutions to the motor redundancy problem. Forces produced by individual fingers
      of one hand were recorded in one-, two-, three-, and four-finger tasks. The
      subjects (n=10) were asked to produce maximal total force (maximal voluntary
      contraction, MVC) and to match a ramp total force profile using different
      combinations of fingers. We found that individual finger forces were smaller in
      multifinger MVC tasks than in single-finger tasks. The deficit increased with the
      number of fingers involved. A saturation effect was observed: when several
      effectors were involved, adding a new effector did not significantly change the
      total force output. The data confirmed the idea that the central neural drive
      arriving at the level of synergies has a certain limit, a ceiling, that cannot be
      exceeded. The central nervous system cannot maximally activate the muscles
      serving all the fingers at the same time. Secondly, during the course of ramp
      trials, forces produced by individual fingers were linearly related to each
      other. Hence, a force sharing pattern was established at the beginning of the
      trial and did not change during the ramp period. A hypothesis is suggested that
      force distribution among fingers may be organized so as to minimize unnecessary
      rotational moment with respect to the functional longitudinal axis of the hand.
      Finally, in the four-finger trials, variance of the total maximal force output in
      ten consecutive attempts was smaller than the sum of variances of the maximal
      individual finger forces. The finding suggests that the control system of the
      motor tasks studied involves at least two levels, a central neural drive level
      and a synergy level. At the synergy level, an intercompensation in individual
      finger force production is observed.

PMID- 9551829
TI  - Intranigral ventral mesencephalic grafts and nigrostriatal injections of glial
      cell line-derived neurotrophic factor restore dopamine release in the striatum of
      6-hydroxydopamine-lesioned rats.
AB  - We have previously reported that grafting of fetal ventral mesencephalic (VM)
      tissue to the nigral region of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned
      rats, in conjunction with glial cell line-derived neurotrophic factor (GDNF)
      injection between nigra and striatum, restores nigrostriatal tyrosine hydroxylase
      (TH) immunoreactivity. In this study, we investigated the electrochemical indices
      of dopamine (DA) release in these grafted animals in the striatum and nigra.
      Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA
      into the medial forebrain bundle. The completeness of lesions was tested by
      measuring methamphetamine-induced rotations. One to two months after 6-OHDA
      administration, fetal VM tissues were grafted in the lesioned nigral area
      followed by injection of GDNF, brain-derived neurotrophic factor (BDNF), or
      phosphate-buffered saline (PBS), along a tract from nigra to striatum. Animals
      receiving transplantation and GDNF, but not BDNF or PBS, injection showed a
      significant decrease in rotation 1-3 months after grafting. High-speed
      chronoamperometric recording techniques, using Nafion-coated carbon fiber
      electrodes, were used to evaluate DA overflow in the striatum. We found that 6
      OHDA lesions resulted in a loss of KCl-induced DA overflow in the urethane
      anesthetized rats. Three months after GDNF-bridged grafting, application of KCl
      elicited DA release both in nigra and striatum. The KCl-evoked DA release area
      was limited to the GDNF-bridging tract in the striatum. On the other hand, KCl
      did not induce DA release in the BDNF- or PBS-bridged grafts. Immunocytochemical
      studies indicated that TH-positive neurons and fibers were found in the nigra and
      striatum after GDNF-bridged grafting. Taken together, our data suggest that fetal
      nigral transplantation and GDNF injection may restore the nigrostriatal DA
      pathway and DA release in these hemiparkinsonian animals and support the
      hypothesis of trophic activity of GDNF on fiber outgrowth from midbrain DA
      neurons.

PMID- 9551830
TI  - Evidence for a strychnine-sensitive mechanism and glycine receptors involved in
      the control of urethral sphincter activity during micturition in the cat.
AB  - Micturition in the decerebrate cat is characterized by a coordinated bladder
      contraction and a simultaneous decrease in external urethral sphincter (EUS)
      efferent activity. Without the suppression of EUS activity, voiding is
      significantly impaired, resulting in a state sometimes referred to as bladder
      sphincter dyssynergia. The aim of the present study was to determine whether
      glycinergic inhibition contributes to the suppression of EUS activity during
      micturition evoked by bladder distension or electrical stimulation of the pontine
      micturition center (PMC) in decerebrate cats. Using subconvulsive intravenous
      doses of strychnine (0.1-0.24 mg/kg), we examined changes in bladder and EUS
      electroneurographic (ENG) activity during micturition. Following subconvulsive
      doses of strychnine, tonic EUS ENG activity increased during bladder filling in
      five of six animals. In the presence of strychnine, it was possible to evoke
      reflex bladder contractions of similar duration and peak pressure to those
      observed before strychnine administration. However, there was an absence of
      suppression of EUS ENG activity during the bladder contractions in all the
      animals. To determine whether the changes in sphincter activity could be due to
      strychnine acting at glycine receptors on EUS motoneurons, sacral spinal tissue
      was processed for a structural protein (gephyrin) associated with the glycine
      receptor. Motoneurons in Onufs nucleus in S1 were identified using choline
      acetyltransferase immunohistochemistry and subsequently processed with a gephyrin
      monoclonal antibody. Abundant gephyrin labeling was evident throughout Onufs
      nucleus. Since Onufs nucleus is made up of EUS and other motoneuron populations,
      a sample of antidromically identified urethral and anal sphincter motoneurons
      were intracellularly labeled with tetramethylrhodamine dextran (TMR-D) and then
      processed with the gephyrin antibody. Using dual-beam confocal microscopy,
      gephyrin immunoreactivity was observed on the soma and proximal processes of
      individual EUS motoneurons in both male and female animals. It was concluded that
      a strychnine-sensitive mechanism contributes to the suppression of sphincter
      activity normally observed during voiding. Although glycinergic inhibition may
      affect several components of the circuitry responsible for micturition, it
      appears that the suppression of EUS motoneurons during micturition may be partly
      due to a direct glycinergic inhibition of the EUS motoneurons.

PMID- 9551831
TI  - Tilt perception during dynamic linear acceleration.
AB  - Head tilt is a rotation of the head relative to gravity, as exemplified by head
      roll or pitch from the natural upright orientation. Tilt stimulates both the
      otolith organs, owing to shifts in gravitational orientation, and the
      semicircular canals in response to head rotation, which in turn drive a variety
      of behavioral and perceptual responses. Studies of tilt perception typically have
      not adequately isolated otolith and canal inputs or their dynamic contributions.
      True tilt cannot readily dissociate otolith from canal influences. Alternatively,
      centrifugation generates centripetal accelerations that simulate tilt, but still
      entails a rotatory (canal) stimulus during important periods of the stimulus
      profiles. We reevaluated the perception of head tilt in humans, but limited the
      stimulus to linear forces alone, thus isolating the influence of otolith inputs.
      This was accomplished by employing a centrifugation technique with a variable
      radius spinning sled. This allowed us to accelerate the sled to a constant
      angular velocity (128 degrees/s), with the subject centered, and then apply
      dynamic centripetal accelerations after all rotatory perceptions were
      extinguished. These stimuli were presented in the subjects' naso-occipital axis
      by translating the subjects 50 cm eccentrically either forward or backward.
      Centripetal accelerations were thus induced (0.25 g), which combined with gravity
      to yield a dynamically shifting gravitoinertial force simulating pitch-tilt, but
      without actually rotating the head. A magnitude-estimation task was employed to
      characterize the dynamic perception of pitch-tilt. Tilt perception responded
      sluggishly to linear acceleration, typically reaching a peak after 10-30 s. Tilt
      perception also displayed an adaptation phenomenon. Adaptation was manifested as
      a per-stimulus decline in perceived tilt during prolonged stimulation and a
      reversal aftereffect upon return to zero acceleration (i.e., recentering the
      subject). We conclude that otolith inputs can produce tilt perception in the
      absence of canal stimulation, and that this perception is subject to an
      adaptation phenomenon and low-pass filtering of its otolith input.

PMID- 9551832
TI  - Activity of thoracic and lumbar epaxial extensors during postural responses in
      the cat.
AB  - This study examined the role of trunk extensor muscles in the thoracic and lumbar
      regions during postural adjustments in the freely standing cat. The epaxial
      extensor muscles participate in the rapid postural responses evoked by horizontal
      translation of the support surface. The muscles segregate into two regional
      groups separated by a short transition zone, according to the spatial pattern of
      the electromyographic (EMG) responses. The upper thoracic muscles (T5-9) respond
      best to posteriorly directed translations, whereas the lumbar muscles (T13 to L7)
      respond best to anterior translations. The transition group muscles (T10-12)
      respond to almost all translations. Muscles group according to vertebral level
      rather than muscle species. The upper thoracic muscles change little in their
      response with changes in stance distance (fore-hindpaw separation) and may act to
      stabilize the intervertebral angles of the thoracic curvature. Activity in the
      lumbar muscles increases along with upward rotation of the pelvis (iliac crest)
      as stance distance decreases. Lumbar muscles appear to stabilize the pelvis with
      respect to the lumbar vertebrae (L7-sacral joint). The transition zone muscles
      display a change in spatial tuning with stance distance, responding to many
      directions of translation at short distances and focusing to respond best to
      contralateral translations at the long stance distance.

PMID- 9551833
TI  - The cat vertebral column: stance configuration and range of motion.
AB  - This study examined the configuration of the vertebral column of the cat during
      independent stance and in various flexed positions. The range of motion in the
      sagittal plane is similar across most thoracic and lumbar joints, with the
      exception of a lesser range at the transition region from thoracic-type to lumbar
      type vertebrae. The upper thoracic column exhibits most of its range in
      dorsiflexion and the lower thoracic and lumbar in ventroflexion. Lateral flexion
      is limited to less than 5 degrees at all segments. The range in torsion is almost
      180 degrees and occurs primarily in the midthoracic region, T4-T11. Contrary to
      the depiction in most atlases, the standing cat exhibits several curvatures,
      including a mild dorsiflexion in the lower lumbar segments, a marked
      ventroflexion in the lower thoracic and upper lumbar segments, and a profound
      dorsiflexion in the upper thoracic (above T9) and cervical segments. The
      curvatures are not significantly changed by altering stance distance but are
      affected by head posture. During stance, the top of the scapula lies well above
      the spines of the thoracic vertebrae, and the glenohumeral joint is just below
      the bodies of vertebrae T3-T5. Using a simple static model of the vertebral
      column in the sagittal plane, it was estimated that the bending moment due to
      gravity is bimodal with a dorsiflexion moment in the lower thoracic and lumbar
      region and a ventroflexion moment in the upper thoracic and cervical region.
      Given the bending moments and the position of the scapula during stance, it is
      proposed that two groups of scapular muscles provide the major antigravity
      support for the head and anterior trunk. Levator scapulae and serratus ventralis
      form the lateral group, inserting on the lateral processes of cervical vertebrae
      and on the ribs. The major and minor rhomboids form the medial group, inserting
      on the spinous tips of vertebrae from C4 to T4. It is also proposed that the
      hypaxial muscles, psoas major, minor, and quadratus lumborum could support the
      lumbar trunk during stance.

PMID- 9551834
TI  - Spatial disparity coding in the superior colliculus of the cat.
AB  - Cells in the superficial layers of the superior colliculus of the cat have mainly
      binocular receptive fields. The aim of the present experiment was to investigate
      the sensitivity of these cells to horizontal spatial disparity. Unit recordings
      were carried out in the superficial layers of the superior colliculus of
      paralyzed and anesthetized cats. Centrally located receptive fields were mapped,
      separated using prisms, and then stimulated simultaneously using two luminous
      bars optimally adjusted to the size of the excitatory region of the receptive
      fields. Only binocular cells were tested, and 65% of these units were found to be
      sensitive to spatial disparities. Some cells (20%) were clearly insensitive to
      spatial disparity and the remaining 15% showed complex, unclassifiable
      interactions. The sensitive cells could be divided into four classes based on
      their disparity-sensitivity profiles: 38% showed excitatory interactions, whereas
      9% showed inhibitory interactions. Moreover, 11% and 7% of the cells responded,
      respectively, to crossed or uncrossed disparities, and were classified as near
      cells and far cells. Whereas the general shapes of the sensitivity profiles were
      similar to those of cells in areas 17-18, selectivity in the superior colliculus
      was significantly coarser. The superficial layers of the superior colliculus
      project topographically to the deep layers of the superior colliculus, which are
      known to contain circuits involved in the control of ocular movements. The
      results thus suggest that disparity-sensitive cells of the superior colliculus
      could feed information to these oculomotor neurons, allowing for the localization
      and fixation of objects on the appropriate plane of vision.

PMID- 9551836
TI  - Ascending propriospinal afferents to area X (substantia grisea centralis) of the
      spinal cord in the rat.
AB  - Area X (the tenth area) of the spinal cord is a region surrounding the central
      canal and extending throughout the spinal cord length. Using anterograde and
      retrograde labeling techniques, ascending propriospinal projections to area X
      were examined in the rat. For anterograde tracing of axons, biotinylated dextran
      was injected into middle-thoracic, lumbar, or sacral-caudal segments. Unilateral
      injections resulted in bilateral labeling of terminals in area X of all segments
      rostral to the injections. The distribution of labeled terminals was conspicuous
      in regions dorsal and lateral to the central canal. The labeled axons were
      derived from the ventrolateral and the lateral cord. They coursed through lamina
      VII, giving off terminal axons. While giving off terminal axons in area X, they
      coursed further rostrally or caudally along the central canal or crossed over the
      central canal to terminate in the contralateral area X. Possible cells of origin
      of these ascending afferents were examined after injections of wheat germ
      agglutinin-horseradish peroxidase into regions surrounding the central canal
      (area X) at the cervical or thoracic level. Retrogradely labeled neurons were
      consistently seen in area X, and laminae VII and VIII of the thoracic and lumbar
      segments. The present study shows that ascending propriospinal axons project to
      area X of all spinal levels rostral to the cells of origin and suggests that some
      of these afferents may originate from neurons in area X and laminae VII and VIII.
      Based on previous data, it is surmised that area X functions, through these
      intricate interconnections, as a site for integration or modulation of somatic or
      nociceptive and visceroceptive sensation.

PMID- 9551835
TI  - Comparison of mesencephalic free-floating tissue culture grafts and cell
      suspension grafts in the 6-hydroxydopamine-lesioned rat.
AB  - Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating
      roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat
      striatum. To further explore the functional efficacy of such grafts, embryonic
      day 13 ventral mesencephalic tissue was grafted either after 7 days in culture or
      directly as dissociated cell suspensions, and compared with regard to neuronal
      survival and ability to normalize rotational behavior in adult rats with
      unilateral 6-hydroxydopamine (6-OHDA) lesions. Other lesioned rats received
      injections of cell-free medium and served as controls. The amphetamine-induced
      rotational behavior of all 6-OHDA-lesioned animals was monitored at various time
      points from 18 days before transplantation and up to 80 days after
      transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically
      processed brains served to assess the long-term survival of grafted dopaminergic
      neurons and to correlate that with the behavioral effects. Additional cultures
      and acutely prepared explants were also fixed and stored for histological
      investigation in order to estimate the loss of dopaminergic neurons in culture
      and after transplantation. Similar behavioral improvements in terms of
      significant reductions in amphetamine-induced rotations were observed in rats
      grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%),
      while control animals showed no normalization of rotational behavior. At 84 days
      after transplantation, there were similar numbers of TH-immunoreactive (TH-ir)
      neurons in grafts of cultured tissue (775 +/- 98, mean +/- SEM) and grafts of
      fresh, dissociated cell suspension (806 +/- 105, mean +/- SEM). Cell counts in
      fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of
      TH-ir cells 7 days after explantation, with an additional 23.1% loss after
      grafting, leaving 8.7% of the original number of TH-ir cells in the intracerebral
      grafts. This is to be compared with a survival rate of 9.1% for the TH-ir cells
      in the cell-suspension grafts. Immunostaining for the calcium-binding proteins
      calretinin, calbindin, and parvalbumin showed no differences in the neuronal
      expression of these proteins between the two graft types. In conclusion, we found
      comparable dopaminergic cell survival and functional effects of tissue-culture
      grafts and cell-suspension grafts, which currently is the type of graft most
      commonly used for experimental and clinical grafting. In this sense the result is
      promising for the development of an effective in vitro storage of fetal nigral
      tissue, which at the same time would allow neuroprotective and neurotrophic
      treatment prior to intracerebral transplantation.

PMID- 9551838
TI  - Correlation of electrophysiology, morphology, and functions in corticotectal and
      corticopretectal projection neurons in rat visual cortex.
AB  - In most mammals the superior colliculus (SC) and the pretectal nucleus of the
      optic tract (NOT) receive direct input from the ipsilateral visual cortex via
      projection neurons from infragranular layer V. We examined whether these
      projection neurons belong to different populations and, if so, whether it is
      possible to correlate the electrophysiological features with the suggested
      function of these neurons. Projection cells were retrogradely labeled in vivo by
      rhodamine-coupled latex beads or fast blue injections into the SC or the NOT 2-5
      days prior to the electrophysiological experiment. Intracellular recordings of
      prelabeled neurons were made from standard slice preparations and cells were
      filled with biocytin in order to reveal their morphology. Both cell populations
      consist of layer V pyramids with long apical dendrites that form terminal tufts
      in layer I. In electrophysiological terms, 12 of the corticotectal cells could be
      classified as intrinsically bursting (IB), while two neurons showed a doublet
      firing characteristic and one neuron was classified as regular-spiking (RS).
      Intracortical microstimulation of cortical layer II/III revealed that SC
      projecting neurons responded optimally to stimulation sites up to a distance of
      1000 microm from the recorded cell. The morphological features of the SC
      projecting cells reveal an apical dendritic tuft in layer I with a lateral
      extension of 300 microm, a mean spine density of 65 spines per 40 microm on the
      apical dendrites located in layer II/III, and a bouton density of 13 boutons per
      100 microm on the intracortical axons. Sixteen NOT-projecting neurons exhibited
      an IB and five cells an RS characteristic. Intracortical microstimulation of
      cortical layer II/III showed that NOT-projecting neurons responded optimally to
      stimulation sites up to a distance of 1500 microm. Their morphological features
      consist of an apical dendritic tuft with a lateral extension of 500 microm, a
      mean spine density of 25 spines per 40 microm on the apical dendrites located in
      layer II/III, and a bouton density of 6 boutons per 100 microm on the
      intracortical axons. When the passive membrane parameters, responses to
      intracortical microstimulation in layer V, the extension of the basal dendritic
      field, and spine densities in layers I or V were compared between SC- and NOT
      projecting cells, no differences were revealed. Differences were only
      consistently found in the supragranular layers, either for morphological
      parameters or for intracortical microstimulation. The results suggest that NOT
      projecting and SC-projecting neurons, although biophysically similar, could
      integrate and transmit different spatial aspects of cortical visual information
      to their target structures.

PMID- 9551837
TI  - Differential localisation of the metabotropic glutamate receptor mGluR1a and the
      ionotropic glutamate receptor GluR2/3 in neurons of the human cerebral cortex.
AB  - Specimens of human cerebral cortex were obtained during neurosurgical operations
      and studied by immunocytochemistry and electron microscopy, using antibodies to
      the metabotropic glutamate receptor subunit mGluR1a and the ionotropic glutamate
      receptor GluR2/3. A small number of non-pyramidal neuronal cell bodies were
      labelled for mGluR1a. Double immunolabelling with mGluR1a and GluR2/3 showed that
      most pyramidal cell bodies were labelled for GluR2/3 but not for mGluR1a. Despite
      the non-colocalisation of these two receptor subtypes in cell bodies, however,
      many dendrites and dendritic spines were double-labelled for mGluR1a and GluR2/3
      at electron microscopy. As there is evidence that most neurons positive for
      GluR2/3 are pyramidal cells, this suggests that mGluR1a is present in dendrites
      of pyramidal neurons, despite absent or low levels of immunoreactivity in their
      cell bodies.

PMID- 9551839
TI  - Mechanical sensitivity of muscle afferents in a nerve treated with colchicine.
AB  - The experiments reported here demonstrate that the mechanical sensitivity of
      peripheral nerve fibres typically seen after injury can be induced without
      overtly injuring the nerve, but by simply applying colchicine topically to the
      nerve. In cats anaesthetised with pentobarbitone sodium, the medial gastrocnemius
      nerve was exposed and 10 mM colchicine applied topically for 15 min. The animals
      recovered from the operation normally and showed no subsequent motor deficit. Six
      days later animals were re-anaesthetised, a laminectomy carried out and responses
      recorded in single afferents at the level of the dorsal root. It was found that
      many afferents, particularly those with conduction velocities in the group II-III
      range, had become sensitive to local mechanical stimulation of the nerve in the
      region treated with colchicine and showed slowly adapting responses to stretch of
      the nerve. Many of the smaller fibres exhibited spontaneous activity.
      Mechanically sensitive afferents exhibited impulse conduction blocks at the
      colchicine-treated site. Some afferents, which appeared to conduct impulses
      normally through the treated region, were associated with muscle receptors having
      normal response properties. However, other muscle receptors were clearly abnormal
      and were insensitive to muscle stretch or contraction or exhibited only phasic
      responses. When the nerve was cut proximal to the colchicine-treated site, some,
      but not all, spontaneous activity was abolished. It was subsequently shown using
      a collision technique that the activity in some axons had its origin in the cell
      body in the dorsal root ganglion. In one experiment, it was shown that after
      nerve section proximal to the colchicine-treated region three of five axons
      switched their activity from a peripheral to a central origin. It is postulated
      that colchicine disrupts fast axonal transport of mechanically sensitive or
      voltage-sensitive ion channels, from the cell body to the peripheral terminals of
      the axons, leading to an accumulation of these channels at the treated site. This
      induces mechanical sensitivity and spontaneous activity. It is postulated that
      interruption of a retrogradely transported signal induces the spontaneous
      activity in the cell body. These experiments suggest that an important influence
      is exerted by the cell body on the peripheral terminals of mechanoreceptors to
      confer on them their normal response properties.

PMID- 9551840
TI  - Complex partial and secondarily generalized seizure patients: cognitive
      functioning prior to treatment with antiepileptic medication. VA Epilepsy
      Cooperative Study 264 Group.
AB  - This investigation of cognitive functioning in patients with symptomatic
      localization-related (partial) epilepsy prior to administration of antiepileptic
      medication is part of a nationwide prospective, double-blind study of drug
      efficacy and longitudinal changes in cognition associated with seizure disorders.
      Recently-diagnosed patients with complex partial or secondarily generalized tonic
      clonic seizures, equated for age, education and IQ, were compared with normal
      controls on a battery of neuropsychological tests: verbal and figural memory
      measures (Rey auditory verbal learning test, Rey Osterrieth complex figure), and
      a brief behavioral toxicity battery comprising measures of motor function,
      concentration and mental flexibility (Lafayette grooved pegboard, controlled word
      association test, Stroop, paced auditory serial addition test [PASAT]). Control
      subjects perform significantly better than both groups of seizure patients on
      several measures of motor speed/integration and memory, specifically the pegboard
      and the RAVLT learning (3-5) and recall trials. Secondarily generalized seizure
      patients show greatest impairment. They perform significantly worse than patients
      with complex partial seizures and control subjects on the controlled word
      association test and the most demanding Stroop color word trial, both measures of
      concentration and mental flexibility. These findings document deficits in memory
      as well as concentration and motor function in complex partial and in secondarily
      generalized seizure patients prior to treatment with antiepileptic medication.

PMID- 9551841
TI  - Transcranial magnetic stimulation: its current role in epilepsy research.
AB  - This paper reviews the current role of transcranial magnetic stimulation (TMS) in
      epilepsy research. After a brief introduction to the technical principles, the
      physiology and the safety aspects of TMS, emphasis is put on how human cortex
      excitability can be assessed by TMS and how this may improve our understanding of
      pathophysiological mechanisms in epilepsy and the mode of action of antiepileptic
      drugs (AEDs). Also, potential therapeutical applications of TMS are reviewed. For
      all aspects of this paper, a clear distinction was made between single-/paired
      pulse TMS and repetitive TMS, since these two techniques have fundamentally
      different scopes and applications.

PMID- 9551842
TI  - A double-blind, placebo-controlled trial of tiagabine given three-times daily as
      add-on therapy for refractory partial seizures. Northern European Tiagabine Study
      Group.
AB  - In a multicentre, double-blind, parallel-group, placebo-controlled trial, a three
      times daily regimen of tiagabine was evaluated as add-on therapy in 154 adult
      patients with refractory partial seizures. A total of 77 patients were randomised
      to treatment in each arm. Tiagabine HCl was titrated from an initial dose of 12
      30 mg/day over 4 weeks. During the 12-week fixed-dose period, there was a
      significant reduction in the median 4-weekly seizure rate for all partial
      seizures and simple partial seizures (P < 0.05 in each case). Furthermore, the
      proportion of patients with a reduction of 50% or more in all partial seizures
      was higher in the tiagabine group than in the placebo group (14 versus 6%),
      though the difference did not achieve statistical significance. The difference
      with respect to simple partial seizures was significant (21 versus 6%, P < 0.01).
      The percentage of patients achieving an increase of at least 50% in the
      proportion of days free of all partial seizures was significantly greater in the
      tiagabine group compared to placebo (14 versus 4%, P<0.01). Tiagabine did not
      appear to influence the plasma concentrations of other concomitant antiepileptic
      drugs and was generally well tolerated, with most drug-related adverse events
      being mild or moderate in severity. The most common adverse events were
      dizziness, asthenia, headache and somnolence. Adverse event incidence was similar
      between tiagabine and placebo groups, except for dizziness which was more common
      with tiagabine (29 versus 10%, P < 0.01). Tiagabine had no significant effects on
      laboratory tests or vital signs. The present study shows that tiagabine, at a
      dose of 10 mg administered three-times daily, which is at the lower end of the
      usual recommended dose range (30-50 mg/day, tiagabine base), is generally well
      tolerated and demonstrates efficacy for the treatment of refractory partial
      seizures.

PMID- 9551843
TI  - Valnoctamide, valpromide and valnoctic acid are much less teratogenic in mice
      than valproic acid.
AB  - The teratogenic properties of valproic acid (VPA) and its analogues depend to a
      great extent on their chemical structure. We investigated the structure
      teratogenicity relationships of VPA, its structural isomer, valnoctic acid (VCA),
      and their two amide analogues, valpromide (VPD) and valnoctamide (VCD),
      respectively. Each substance was injected (3 mmol/kg) in NMRI-mice on the morning
      of day 8 of gestation. Embryolethality, fetal weight and exencephaly rates were
      recorded on day 18 of gestation. VPA caused 53% exencephaly, VPD induced 6%, VCA
      and VCD produced only 1% exencephaly (control values between 0 and 1%). VPA
      treated mice also had increased embryolethality rates (52%). There was no
      significant change of embryolethality in the other treatment groups.
      Pharmacokinetic studies showed that VCD was eliminated from plasma at a slower
      rate than VPA. Also, the residual teratogenic activity of VPD was not accounted
      for by the relatively small amounts of its hydrolysis product VPA. This study
      indicates that VPD, VCA and VCD were distinctly less teratogenic than VPA.
      Apparently the amidation of the free carboxylic group and/or methyl-substitution
      at the beta-position of the carbon chain greatly decreased the teratogenic
      activity of VPA.

PMID- 9551844
TI  - Decreased brainstem seizure thresholds and facilitated seizure propagation in
      mice exposed to repeated flurothyl-induced generalized forebrain seizures.
AB  - We recently have described a novel model of epileptogenesis utilizing the
      inhalant chemoconvulsant, flurothyl (Applegate et al., 1997; Samoriski and
      Applegate, 1997). The hallmark feature of this model is a change in behavioral
      seizure phenotype from a forebrain seizure, observed during the initial flurothyl
      exposures, to a brainstem seizure, elicited by flurothyl, after a 28-day
      stimulation free incubation period. In this study, we sought to establish the
      basis for this change in behavioral seizure response. To this end, we examined
      the effects of exposure to this paradigm on the generalized brainstem seizure
      threshold and on the propagation of forebrain seizures onto the brainstem seizure
      substrate. Ten mice were given flurothyl-induced generalized forebrain seizures
      on 8 consecutive days (induction phase). The other ten mice were not exposed to
      the flurothyl induction paradigm and served as controls. Minimal corneal
      electroconvulsive shock (mECS--20 mA) was used to assay whether there was any
      change in the animals' generalized brainstem seizure thresholds at 3, 14 and 28
      days following the last flurothyl seizure trial. Mice that were exposed to
      flurothyl exhibited a progressive increase in the percentage of animals having a
      mECS-induced brainstem seizure when tested at 3 (40%), 14 (70%) and 28 (90%) days
      following the last flurothyl seizure. Control mice rarely had a brainstem seizure
      at any of the three time points tested, mostly forebrain seizures were observed.
      These results suggest that there is a significant progressive lowering of the
      brainstem seizure threshold, during the incubation phase of the flurothyl
      paradigm, which is coincident with the previously reported time course of change
      in the behavioral seizure phenotype observed using this flurothyl model
      (Applegate et al., 1997; Samoriski and Applegate, 1997). Following mECS testing,
      mice were implanted with bipolar electrodes and kindled from the olfactory bulb
      (OB). Mice exposed to the flurothyl paradigm demonstrated significantly faster
      kindling rates, longer afterdischarge durations. and longer durations of and
      latencies to stage 5 seizures compared to controls. Furthermore, animals exposed
      to the flurothyl protocol demonstrated an increase in the expression of brainstem
      seizures after focally-elicited OB afterdischarges. These results suggest that
      there is an increased interaction between the forebrain and brainstem seizure
      systems after exposure to this model of epileptogenesis. Together, results
      indicate that the change in behavioral seizure phenotype observed following
      exposure to our flurothyl paradigm are promoted by both decreases in brainstem
      seizure thresholds and facilitated forebrain seizure propagation onto the
      brainstem seizure system.

PMID- 9551845
TI  - Inhibition of pentylenetetrazol-induced seizures in rats by prostaglandin D2.
AB  - This study was undertaken to evaluate the role of brain PGD2 activity during PTZ
      induced seizures in rats. Potentiation of endogenous PGD2 activity caused an anti
      convulsant effect. Thus, after PGD2 injection (5 microg/icv) the latency of
      generalized tonic clonic convulsions was prolonged. ZK 118.182, a stable analogue
      of PGD2, dose-dependently inhibited the incidence and the intensity of seizures
      when injected at doses of 1-100 ng/icv. But on the other hand, inhibition of PGD2
      activity either by a D-type PG receptor antagonist (AH 6809; 50 ng/icv) or by a
      PGD synthase inhibitor (sodium selenite; 0.2 microg/icv) produced a proconvulsant
      effect by increasing the incidence and the intensity of the seizures. These
      findings indicate that endogenous PGD2 activity in the brain may have a specific
      inhibitory role for the initiation and propagation of PTZ induced seizures in
      rats.

PMID- 9551846
TI  - Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with
      phenytoin.
AB  - Phenytoin has been reported to exert variable anticonvulsant effects in the
      kindling model of complex partial seizures. Phenytoin is only water soluble at a
      pH of more than 10, and it has been suspected that poor absorption of the drug is
      responsible for its lack of effect in some experiments. Recently, fosphenytoin, a
      prodrug of phenytoin, has been developed by phosphorylating phenytoin which makes
      the drug water soluble at physiological pH while it is rapidly transformed to
      phenytoin after injection. This study examined the anticonvulsant profile and the
      absorption after intraperitoneal injection of fosphenytoin, compared to its
      parental drug phenytoin. The pharmacokinetic parameters of phenytoin and
      fosphenytoin were compared by determining plasma levels of phenytoin after i.p.
      injection of 50 mg/kg phenytoin or the equivalent dose of 84 mg/kg of
      fosphenytoin in non-kindled female Wistar rats. After both injections the maximal
      plasma concentration of phenytoin was about 30 microg/ml. The relative
      bioavailability of fosphenytoin was 83%. In contrast to phenytoin, failed
      injections resulting in non-detectable plasma concentration of phenytoin were
      almost absent after fosphenytoin. In fully kindled female Wistar rats,
      fosphenytoin dose-dependently increased the focal seizure (afterdischarge)
      threshold. Seizure severity and duration at threshold were reduced only after the
      highest does of fosphenytoin tested (84 mg/kg). Thus, fosphenytoin showed
      anticonvulsant properties similar to phenytoin in amygdala kindled rats. We
      conclude that fosphenytoin is an adequate and reliable substitute for the
      parenteral injection of phenytoin in experimental seizure models of rats.

PMID- 9551847
TI  - Heart rate variability in patients with epilepsy.
AB  - Autonomic function was studied by the use of spectral analysis of heart-rate
      variability in patients with epilepsy in relation to type of epilepsy and anti
      epileptic drug therapy. A total of 21 patients with juvenile myoclonic epilepsy
      (JME) and 21 with temporal lobe epilepsy (TLE) were included; 18 patients were
      treated with carbamazepine (CBZ), 16 with valproate (VPA) and seven with
      phenytoin (PHT). One healthy drug free control, matched for age and sex, was
      selected for each patient. Patients and controls underwent an ambulatory 24 h
      EKG. Heart-rate variability was analyzed in time and frequency domains. Patients
      with TLE had significantly lower S.D. of the RR-intervals, lower low frequency
      power and a lower low frequency/high frequency power ratio than their controls. A
      lower low frequency/high frequency power ratio was the only significant
      difference between the JME patient group and their controls. Treatment, however,
      may have had a considerable influence on the heart rate variability in the
      epilepsy patients. Patients on CBZ had significantly lower S.D. of RR-intervals,
      low frequency power and a low frequency/ high frequency power ratio than did
      their matched healthy drug free controls. The ratio of low frequency/high
      frequency power was also lower in patients on VPA compared with their controls,
      but apart from that no differences could be demonstrated between this treatment
      group and the controls. In conclusion, patients with epilepsy appear to have an
      altered autonomic control of the heart, with a reduction in some heart-rate
      variability measures, suggesting a decreased sympathetic tone, which may be
      related to the drug therapy or the epilepsy as such. Further studies are
      warranted to explore these changes and their possible relevance for sudden death
      in epilepsy.

PMID- 9551848
TI  - Delta-aminolevulinic acid-induced lipid peroxidation in rat kidney and liver is
      attenuated by melatonin: an in vitro and in vivo study.
AB  - Acute intermittent porphyria (AIP) is a genetically inherited disease
      characterized by a partial block in liver heme biosynthesis and by increased
      urinary excretion of the delta-aminolevulinic acid (ALA). Recently, it has been
      proposed that the toxic effects of ALA are related to the generation of free
      radicals. In the present study the in vitro and in vivo effect of melatonin, a
      recently described antioxidative agent, on ALA-induced lipid peroxidation in rat
      liver and kidney was determined. The concentration of malonaldehyde (MDA) and 4
      hydroxyalkenals (4-HDA) was assayed as an index of induced membrane oxidative
      damage. In vitro melatonin protected, in a concentration-dependent manner,
      against ALA-induced lipid peroxidation in liver and kidney homogenates. In in
      vivo experiments as well, it was demonstrated that ALA (40 mg/kg)-induced lipid
      peroxidation in liver and kidney was reduced by acute melatonin (10 mg/kg)
      treatment. The results support the involvement of free radicals in ALA toxicity
      and show that in vitro and in vivo melatonin confers protection against this
      toxicity, likely due to the antioxidative capability of the indole.

PMID- 9551849
TI  - Stimulatory effect of melatonin on the 5'-monodeiodinase activity in the liver,
      kidney, and brown adipose tissue during the early neonatal period of the rabbit.
AB  - The response of type I 5'-monodeiodinase activity (5'-MD) to a s.c. injection or
      oral administration of melatonin was studied in 3-, 5-, and 7-day-old rabbits.
      Melatonin-treated animals showed higher activity of the type I 5'-MD in the liver
      and kidney and of type II 5'-MD in brown adipose tissue (BAT). This respond to
      melatonin treatment was age dependent. The stimulatory effect of melatonin on
      renal 5'-MD activity was observed only in 3- and 5-day-old rabbits and in the
      liver and BAT during the first week of life. Oral melatonin administration tended
      to exert a more marked effect on enzyme activity than s.c. injection of the
      hormone. Changes in 5'-MD activities were accompanied by an increase in serum
      iodothyronine (T4, T3, and rT3) concentrations. The T3 and rT3 increases may
      result from the deiodinating processes by the type I 5'-MD and 5-MD,
      respectively, whereas the rise in the serum T4 was probably due to the
      stimulatory effect of melatonin on the secretory activity of the thyroid gland
      itself. These results are the first description of the effects evoked by
      melatonin treatment during the early neonatal period in newborns of the altricial
      type.

PMID- 9551850
TI  - Melatonin excretion is not related to sleep in the elderly.
AB  - We examined the association between 6-sulphatoxymelatonin (6-SMT) excretion and
      sleep in 68 volunteers 60-79 years of age who complained of insomnia or
      depression. An Actillume wrist monitor was worn for 5-7 consecutive days and
      nights in home-living conditions. Activity was used to estimate total sleep time
      (TST) and wake after sleep onset (WASO). Throughout two 24 hr periods, urine was
      collected approximately every 2 hr during the day and after any voidings during
      the sleep period. During the next week, subjects spent 5 nights and 4 days in the
      laboratory. Sleep was measured and scored with standard polysomnographic
      techniques. Urine was collected, as for home recording, on days 1 and 4. Urinary
      concentrations of 6-SMT were assayed. Cosine-fitting of urine data across both
      days at home and both laboratory collections established the mesors and
      amplitudes of 24 hr 6-SMT excretion rhythms, but neither was significantly
      correlated with sleep. Mean and peak 6-SMT excretion during the sleep period was
      also determined. Significant correlations were found between mean 6-SMT during
      the laboratory sleep period and TST and WASO. However, these associations were
      not independent of circadian timing: sleep was better when sleep occurred near
      the circadian acrophase of 6-SMT excretion. These data indicate that low
      melatonin production may not be an important factor in insomnia among the
      elderly.

PMID- 9551851
TI  - Effect of continuous melatonin infusions on steady-state plasma melatonin levels
      in rats under near physiological conditions.
AB  - It was the aim of this study to measure the actual amount of melatonin required
      for elevating the circulating hormone from low daytime levels to the 10-fold
      higher nocturnal steady-state concentrations in rats. For this purpose,
      escalating doses of melatonin were continuously infused into the right jugular
      vein and blood samples were repeatedly drawn from the left jugular vein for a
      period of 2 hr in freely moving catheterized rats. In order to achieve an about
      10-fold elevation of the plasma melatonin concentration, 500 ng melatonin/hr had
      to be infused, i.e., about 300 times the normal nocturnal melatonin content of
      the pineal. Infusions of up to 61 ng melatonin/hr (equivalent to the melatonin
      content of 40 pineals at darkness) failed to cause a significant rise of the low
      daytime steady-state concentrations in the blood. If the dose of 500 ng
      melatonin/h was infused at night, a less-pronounced rise of the blood levels was
      observed, as compared to that caused by the infusion of the same dose during
      daytime. No differences were found in the rate of metabolism between daytime and
      nighttime. The results of this study indicate 1) that the low basal
      concentrations of melatonin in the blood are not affected by an increased
      melatonin supply up to a certain critical threshold, 2) that the rat pineal gland
      would have to release all its melatonin content almost every 10 sec in order to
      sustain the elevated steady-state level of melatonin in the circulation during
      the dark period, and 3) that significant day/night differences exist in the
      disposition of circulating melatonin if administered in near physiological
      amounts and under near physiological conditions.

PMID- 9551852
TI  - Regulation of calcium influx and phospholipase C activity by indoleamines in
      dinoflagellate Crypthecodinium cohnii.
AB  - Exogenous indoleamines such as melatonin and 5-methoxytryptamine have been shown
      to induce cyst formation (encystment) in many species of dinoflagellate.
      Induction of inositol phosphates formation by indoleamine has previously been
      demonstrated in Crypthecodinium cohnii. In addition, depletion of extracellular
      Ca2+ blocks the indoleamine-induced encystment. In the present study, 12
      indoleamines (including melatonin and related compounds) were examined for their
      abilities to induce Ca2+ influx, inositol phosphates formation, and encystment in
      C. cohnii. The results showed that melatonin, 5-methoxytryptamine, and the
      peptide toxin mastoparan stimulated 45Ca2+ influxes in dose- and time-dependent
      manners. The EC50 values of 5-methoxytrypramine and mastoparan to stimulate
      45Ca2+ uptake were 2 mM and 35 microM, respectively. The 5-methoxytryptamine- and
      mastoparan-induced 45Ca2+ influx were partially attenuated by the calcium channel
      blockers, verapamil and ruthenium red. A series of indoleamines were examined for
      their structure-activity relationship on the induction of encystment and
      formation of inositol phosphates. Melatonin-induced inositol phosphates formation
      was completely blocked by U73122, indicating the possible involvement of
      phospholipase C. Taken together, we conclude that indoleamines may induce
      encystment of the dinoflagellate C. cohnii via parallel activation of
      phospholipase C and Ca2+ influx signaling pathways. However, activation of
      phospholipase C and Ca2+ influx are not always necessary or sufficient for
      inducing encystment. Also, these data provided the first direct evidence of a
      Ca2+ influx regulating mechanism in dinoflagellate C. cohnii.

PMID- 9551853
TI  - Daily and photoperiodic 2-125I-melatonin binding changes in the pars tuberalis of
      the Syrian hamster (Mesocricetus auratus): effect of constant light exposure and
      pinealectomy.
AB  - Using quantitative autoradiography, 2-125I-melatonin binding was investigated
      throughout the light/dark cycle in the pars tuberalis (PT) of the pituitary of
      adult Syrian hamsters kept for 8 weeks either in long or short photoperiod (LP or
      SP, respectively). Melatonin receptor density in the PT displayed photoperiod
      dependent daily variations (maximal values in LP). Indeed, in LP, melatonin
      receptor density underwent strong daily variations with maximal values during the
      first half of the light period and minimal values at the end of the night. These
      variations depended on changes in the maximal binding (Bmax) without differences
      in the dissociation constant (Kd). In contrast, PT melatonin receptor density was
      constant and at a very low level throughout the light:dark cycle in SP exposed
      animals. Daily PT melatonin receptor density variations of LP exposed animals
      were abolished by pinealectomy or continuous light exposure. These results show
      clearly that both at the daily and at the seasonal level the regulation of PT
      melatonin receptors is strongly dependent on circulating melatonin concentrations
      in the Syrian hamster, but that other regulatory factors, yet unclarified, might
      also play a role.

PMID- 9551855
TI  - Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells:
      implications for Parkinson's disease.
AB  - It was recently reported that low doses of 6-hydroxydopamine (6-OHDA) induce
      apoptosis of naive (undifferentiated) and neuronal (differentiated) PC12 cells,
      and this system has been proposed as an adequate experimental model for the study
      of Parkinson's disease. The mechanism by which this neurotoxin damages cells is
      via the production of free radicals. Given that the neurohormone melatonin has
      been reported 1) to be a highly effective endogenous free radical scavenger, 2)
      to increase the mRNA levels and the activity of several antioxidant enzymes, and
      3) to inhibit apoptosis in other tissues, we have studied the ability of
      melatonin to prevent the programmed cell death induced by 6-OHDA in PC12 cells.
      We found that melatonin prevents the apoptosis caused by 6-OHDA in naive and
      neuronal PC12 cells as estimated by 1) cell viability assays, 2) counting of the
      number of apoptotic cells, and 3) analysis and quantification of DNA
      fragmentation. Exploration of the mechanisms used by melatonin to reduce
      programmed cell death revealed that this chemical mediator prevents the 6-OHDA
      induced reduction of mRNAs for several antioxidant enzymes. The possibility that
      melatonin utilized additional mechanisms to prevent apoptosis of these cells is
      also discussed. Since this endogenous agent has no known side effects and readily
      crosses the blood-brain-barrier, we consider melatonin to have a high clinical
      potential in the treatment of Parkinson's disease and possibly other
      neurodegenerative diseases, although more research on the mechanisms is yet to be
      done.

PMID- 9551854
TI  - N-acetyl-serotonin (normelatonin) and melatonin protect neurons against oxidative
      challenges and suppress the activity of the transcription factor NF-kappaB.
AB  - It is now well established that the formation of free radicals and oxidative
      stress-induced neuronal cell death can be involved in various neurodegenerative
      disorders, including Alzheimer's disease and Parkinson's disease. The pineal
      hormone melatonin has been suggested to be a neuroprotective antioxidant. To
      better understand the molecular mechanism of this activity, we compared the
      ability of melatonin and its precursor, N-acetyl-serotonin (normelatonin), to
      protect human neuroblastoma SK-N-MC cells and primary cerebellar granular neurons
      against oxidative stress. We found that normelatonin and melatonin have
      differential neuroprotective effects depending on the neuronal cell type.
      Normelatonin was more protective against hydrogen peroxide (H2O2) and glutamate
      induced cell death in SK-N-MC cells compared to melatonin which was more
      effective to protect primary cerebellar granular neurons against the toxicity of
      H2O2, glutamate and N-methyl-D-aspartate when compared to normelatonin. At the
      molecular level, we tested the capacity of normelatonin and melatonin to inhibit
      the oxidative stress-induced NF-kappaB activation in both neuronal systems.
      Whereas normelatonin was more potent in the suppression of the activation of NF
      kappaB by H2O2 in SK-N-MC cells compared to melatonin, no apparent differences in
      the extent of suppression could be detected in primary neurons. Normelatonin's
      and melatonin's neuroprotective activity in SK-N-MC neuroblastoma cells may be
      mediated by the suppression of NF-kappaB activation.

PMID- 9551856
TI  - Auto-regulation of thyroid hormone receptor genes during metamorphosis: roles in
      apoptosis and cell proliferation.
AB  - Amphibian metamorphosis is an excellent model system for studying postembryonic
      development in vertebrates. It involves specific degeneration of larval cells
      through programmed cell death with apoptotic morphology and selective
      proliferation and differentiation of adult cell types. Thyroid hormone (T3) plays
      a causative role in this process and the effects of T3 is presumed to be mediated
      by T3 receptors (TRs). Studies in other systems have suggested that TRs function
      as heterodimers formed with RXRs (9-cis retinoic acid receptors) and require the
      presence of various cofactor in transcriptional activation and repression in the
      presence and absence of T3, respectively. The T3-induced transcriptional
      activation leads to chromatin remodeling which may involve some of the cofactors.
      Recent investigation on receptor expression has implicated a role of TRs in T3
      induced apoptosis in larval tissues and proliferation of adult cell types.
      Functional studies in tadpoles and developing embryos have provide strong support
      for such a role and further demonstrate the importance of RXR in mediating the
      effect of T3.

PMID- 9551857
TI  - The generation of fiber diversity during myogenesis.
AB  - Adult muscle is composed of different fiber types distinguished by their speed of
      contraction and metabolism. The generation of these differences is related both
      to the sequence in which muscle fibers form and to differences between the
      myogenic cells involved. Fibers form in two successive waves (primary and
      secondary) whose time of appearance can be correlated with the existence of
      successive populations of myogenic cells (embryonic and fetal). The differences
      between fibers arise through an interplay between heritable cellular commitment,
      where cells are preprogrammed to produce particular types of fiber and influences
      from the limb environment. The techniques of genetically marking cells and clonal
      analysis in vivo and in vitro are starting to reveal the relationship between
      these different influences. Although the process of myogenesis is similar in
      birds and mammals it is likely that cell autonomous behaviour plays a more
      important role during avian development as compared to mammals. The
      identification of muscle specific transcription factors has provided some clues
      to the mechanisms by which development is controlled but the expression of
      relatively few of these has been correlated with the sequence of events seen in
      myogenesis.

PMID- 9551858
TI  - Cell-cell signaling during neurogenesis: some answers and many questions.
AB  - Development of a multicellular organism requires that cells communicate with each
      other in order to regulate their growth, organize into tissues and coordinate
      their function. This cell-cell communication is mediated by signals cells receive
      (or send) between each other and from the environment. The signaling can be a
      short range remote signaling (through secreted signaling molecules), contact
      signaling (via plasma membrane bound molecules, gap junctions) or a long range
      signaling (through hormones). In this article, I have reviewed the recent
      advances on the role of cell-cell signaling in the development of the embryonic
      nervous system of the fruitfly Drosophila melanogaster and discussed some of the
      open questions raised by these studies. It discusses the contributions of the
      neurogenic genes Notch and Delta and the signaling pathways controlled by
      wingless, patched and hedgehog in neuroblast formation, neuroblast identity
      specification and neuroblast lineage elaboration.

PMID- 9551859
TI  - Tissue and developmental distribution of Six family gene products.
AB  - To examine the presence and distribution of Six family gene products in a variety
      of tissues at various developmental stages and in various cell types, we prepared
      specific antibodies against recombinant Six gene products. The distribution of
      Six2 and Six4 was examined by immunostaining in the developing mouse embryo.
      Production of Six2 was detected at E8.5 mainly in the mesenchyme, while Six4 was
      present in nuclei of neuronal cells in the peripheral region of the mantle layer
      of developing brain and spinal cord and in various ganglia at E10.5 and E11.5.
      Specific DNA binding activities of the Six proteins were analyzed by gel
      retardation super-shift assays using nuclear extracts from different rat tissues
      and cell lines. Six5 was the dominant isoform observed in the adult kidney, liver
      and lung but not in the brain. Six4 was not detected in all tested adult tissues,
      however, it was present in embryonic (FD21) lung nuclear extracts. In contrast,
      Six4 was detected in a variety of cultured cell lines, including HeLa, 3T3, MDCK
      and C2C12. Our results suggest that Six4 plays a specific role in the
      differentiation or maturation of neuronal cells, while Six5 is an adult type Six
      gene isoform product and is distributed in the kidney, liver and lung.

PMID- 9551860
TI  - Formation of polar cytoplasmic domains (teloplasms) in the leech egg is a three
      step segregation process.
AB  - Segregation and proliferation of mitochondria, leading to formation of the
      teloplasms (pole plasms), were studied in eggs of the leech T. rude by
      immunocytochemistry, fluorescent time lapse video imaging, confocal and electron
      microscopy. The translocation of mitochondria was analyzed after loading the egg
      with either Rhodamine 123 or a Mitotracker. Mitochondrial proliferation was
      assessed after pulse labeling with BrdU. The involvement of the cytoskeleton in
      the segregation process was determined by drug action. The teloplasms form during
      the first interphase as consequence of a 3-step sequential process of
      mitochondrial redistribution throughout the egg cytoplasm. The first step is a
      microtubule dependent process of ectoplasm thickening due to centrifugal
      mitochondrial transportation from the neighboring endoplasm. During the second
      step mitochondria move in the plane of the ectoplasm to become concentrated at
      the wall of rings (polar rings) and bands of contraction. This process appears to
      mostly depend on actin. The furrowing pattern of the egg during this step can be
      modified by cold treatment and seems to be determined during oogenesis. During
      the third step the ectoplasm flows to either of the poles in conjunction with
      bipolar displacement of the polar rings and shortening of the contraction bands.
      This step depends on both microtubules and microfilaments. Mitochondria of first
      interphase eggs have three special features: (1) they move in clusters, (2) their
      movement depends on both microtubules and microfilaments and (3) they proliferate
      continuously. During the first interphase the polarized meiotic egg becomes a
      bipolar cell.

PMID- 9551861
TI  - Expression and function of tap in the gustatory and olfactory organs of
      Drosophila.
AB  - We have recently described the identification of a gene, tap, which encodes a
      bHLH protein expressed in one neuron of each larval chemosensory organ. Here we
      show that tap is expressed at a late stage in the development of one type of
      adult chemosensory organ, the gustatory bristles of the leg, wing and proboscis.
      We also show that tap is expressed very early in the development of a second type
      of chemosensory receptors, the olfactory organs of the antenna. The results of
      behavioral experiments suggest that the ectopic expression of tap affects the
      response to sugar and salt.

PMID- 9551862
TI  - Cloning of the Xenopus integrin alpha(v) subunit and analysis of its distribution
      during early development.
AB  - One striking feature of the integrin alpha(v) subunit is its ability to associate
      with at least five different beta subunits (beta1, beta3, beta5, beta6 and beta8)
      to form functional receptors. These receptors are involved in diverse biological
      processes, such as differentiation, cell adhesion and migration. Here we report
      the cloning of the Xenopus homolog of the integrin alpha(v) subunit. Integrin
      alpha(v) mRNA and protein are maternally supplied and present throughout
      development. During gastrulation and neurulation alpha(v) protein appears on cell
      membranes of all three germ layers. In tailbud stage embryos great amounts of the
      alpha(v) protein can be observed in the inner layer of the ectoderm and in the
      endothelial cells lining the pharynx and gut.

PMID- 9551863
TI  - Blastomeres and cells with mesendodermal fates of carp embryos express cth1, a
      member of the TIS11 family of primary response genes.
AB  - The carp cth1 gene, related to the mammalian TIS11 family of primary response
      genes, encodes a novel fish protein with two putative CCCH zinc fingers. This
      report describes the RNA expression of this gene during cleavage, blastula and
      gastrula stages of carp embryos. Cth1 mRNA is present in all cleavage stage
      blastomeres as a maternal message. After the late blastula stage, the maternal
      expression decreases, revealing a spot of higher expression at the margin of the
      blastoderm of the dome stage embryo. Further decrease of the maternal message
      reveals a ring of cth1 expressing cells at the blastoderm margin from the stage
      of 40% epiboly onwards. By alpha-amanitin treatment we established that this
      local cth1 expression is of zygotic origin. At the onset of gastrulation the
      cells of the cth1 ring involute, starting with those in the shield region, and at
      approximately 60% epiboly the ring is fully involuted and occupies the hypoblast
      layer. All cth1 transcripts have disappeared at completion of epiboly. We discuss
      a possible role for the putative cth1 protein during cleavage and gastrulation.

PMID- 9551864
TI  - HB-GAM/pleiotrophin: localization of mRNA and protein in the chicken developing
      leg.
AB  - The heparin-binding growth-associated molecule HB-GAM (also named pleiotrophin)
      is a developmentally-regulated protein that belongs to a new family of heparin
      binding molecules with putative functions during cell growth and differentiation.
      In order to study the localization of HB-GAM during chicken embryogenesis, we
      produced specific monoclonal antibodies to this factor. HB-GAM protein is first
      observed at stage 23 in the developing nervous system and later in the forming
      cartilage. We present an investigation of the HB-GAM mRNA expression and HB-GAM
      protein distribution in the developing leg by in situ hybridization and
      immunocytochemical studies. We focused our attention on the development of the
      tibia, where the HB-GAM protein appears at stage 27-28, i.e., just after the
      condensation of the mesodermal precursor cells of the chondrocytes. The protein
      then progressively accumulates in the central part of the embryonic cartilage
      (diaphysis). It persists until stage 42-44 in the regions where hypertrophic
      cartilage is being replaced by bone marrow. In contrast to the protein, the
      transcript is first detected at stage 26-27 and later expressed essentially in
      the epiphysis until stage 37. Therefore the localization of the mRNA does not
      parallel that of the protein and our data suggest a long half-life of the protein
      in the hypertrophic cartilage. In addition, the layer of stacked cells
      surrounding the cartilage core (usually considered as the osteoprogenitor cells)
      clearly expresses the HB-GAM message between stages 30-37 whereas differentiated
      osteoblasts do not. Furthermore, the distribution of HB-GAM protein in the
      osteoblast/osteoid layer suggests an involvement of this protein in early steps
      of osteogenesis. HB-GAM is absent from the newly formed bone.

PMID- 9551865
TI  - Direct transdifferentiation in the vertebrate retina.
AB  - Transdifferentiation is the process by which differentiated cells alter their
      identity to become other, distinct cell types. The conversion of neural retina
      into lens epithelium is one of the most spectacular examples of
      transdifferentiation. We show that the redirection of cell fate from neural
      retina to lens and subsequent transdifferentiation is independent of cell
      replication as it occurs in growth-arrested cell populations. Using DNA
      ratiometry of individual cells in these cultures we show that, indeed, individual
      amitotic cells do transdifferentiate. Hence, choice of fate in
      transdifferentiating cells does not rely on a "community effect" but instead can
      be categorized as a <<leadership effect>> For lack of overt lens progenitors, and
      most importantly, for its mitotic independence, we conclude that lens colony
      formation in vitro does occur by direct transdifferentiation and not by clonal
      proliferation of progenitor cells.

PMID- 9551866
TI  - Local increase level of chondroitin sulfate induces changes in the
      rhombencephalic neural crest migration.
AB  - Numerous studies suggest that chondroitin sulfate proteoglycan (CSPG) inhibits
      neural crest cells (NCC) migration at the trunk level. However, its action on the
      cephalic neural crest is not clear. To determine this action, we have
      microinjected 0.5 nl of different concentrations of chondroitin sulfate (CS) at
      the anterior rhombencephalon level in 9 stage chick embryos, as well as
      subgerminally administering beta-D-xyloside to 8 stage chick embryos. Beta-D
      xyloside disrupts CSPG synthesis, producing an increase in CS free chains in
      several embryonal anlages. Chondroitin sulfate microinjected embryos and beta-D
      xyloside treated embryos were reincubated until attaining 12 stage. Results
      obtained for both experimental groups were similar. Immunoreactivity with HNK-1
      antibody revealed that NCC did not migrate, remaining near the rhombencephalon
      dorsal wall; in addition, several NCC did not separate from the neural fold,
      becoming invaginated towards the rhombencephalon cavity. Our findings indicate
      that an increase in CS free chains in cephalic neural crest migratory routes not
      only disrupts their migration, but also impedes delamination and detachment of
      the rhombencephalic neuroepithelium NCC. These data suggest that the inhibitory
      action upon the neural crest migration attributed to CSPG may rest on its
      glycosaminoglycan (GAG). We cannot, however, rule out the possibility that
      increases in other GAGs apart from CS, may produce similar effects on neural
      crest migration.

PMID- 9551867
TI  - Laminin fragment E4 inhibition studies: basement membrane assembly and embryonic
      lung epithelial cell polarization requires laminin polymerization.
AB  - Laminins (LMs), the main constituents of basement membranes (BMs), are
      heterotrimeric glycoproteins composed of alpha, beta, and gamma chains held
      together by disulfide bonds. In the presence of Ca2+, some laminins, such as
      laminin-1 self-assemble into a polymer through the interaction of their three NH2
      termini. Here we exposed lung organotypic cultures to a proteolytic fragment of
      laminin-1 that blocks laminin polymerization. This fragment, referred as E4,
      comprises the outer globular region of laminin beta1 chain. Inhibition of laminin
      polymerization in lung organotypic cultures resulted in impaired basement
      membrane assembly and failure of epithelial cells to polarize. In addition, we
      found that in control organotypic cultures, the bronchial smooth muscle cells
      were arranged in concentric layers around the newly formed epithelium. However,
      in E4-treated cultures, the smooth muscle cells were in disarray. Exposure of
      organotypic cultures to laminin-1 proteolytic fragment P1', that comprises part
      of alpha1, beta1, and gamma1 chains, but does not overlap with fragment E4, had
      no effect in basement membrane assembly. Exposure to fragment E4 also caused an
      increased release of laminin-1 into the culture medium, suggesting a failure to
      retain laminin at the epithelial-mesenchymal interface. These studies provide the
      first direct evidence linking epithelial cell polarization to laminin
      polymerization at the epithelial-mesenchymal interface and assign a key role to
      the outer globular region of laminin beta1 chain.

PMID- 9551868
TI  - Identification of elf1, a beta-spectrin, in early mouse liver development.
AB  - Beta-spectrins play essential roles in cell-cell interactions and in the
      maintenance of cell polarity. Our aim was to identify beta-spectrin genes
      important for the establishment of hepatocyte polarity and differentiation. Using
      subtractive screening of cDNA libraries from early embryonic mouse livers (post
      coital days 10, 11, and 12), we have isolated elf1 (embryonic liver fodrin 1), a
      differentially expressed beta-spectrin or fodrin (betaSpIIsigmaI). Elf1 encodes a
      220-amino acid protein with an NH2 terminal actin-binding domain. In situ
      hybridization studies demonstrate elf1 expression initially in day 10 embryonic
      heart tissue, then in day 11-11.5 hepatic tissue. These studies suggest that elf1
      may play a role in the emergence of hepatocyte polarity during liver development.

PMID- 9551869
TI  - Differentiation of the mouse embryoid bodies grafted on the chorioallantoic
      membrane of the chick embryo.
AB  - In order to test the developmental potential of the mouse embryonic-stem-cell
      derived embryoid bodies as chorioallantoic grafts, the embryoid bodies were
      transplanted to the chorioallantoic membrane (CAM) of the chick embryo. The graft
      implantation was achieved if the embryoid bodies were transferred to the CAM into
      the blood drop created by gentle laceration of a CAM blood vessel. The resulting
      tumors were recovered after 10 days, when they were rounded white elevations, up
      to 1 mm big. Histological analysis showed that they were made of groups of
      compacted epithelial-like cells and fibroblast-like spindle shaped cells divided
      by the CAM mesenchyme. The grafting caused angiogenic response of the CAM. Blood
      vessels converged toward the tumor and spread through the CAM mesenchyme among
      the groups of condensed cells. Although the embryonic bodies were able to implant
      to the CAM of the chick, their differentiation did not result in a wide variety
      of differentiated cell types or in the formation of complex structures resembling
      morphogenesis. Thus in comparison with in vitro differentiation of embryoid
      bodies on an adhesive substrate, or in vivo differentiation under the mouse
      kidney capsule, the differentiation potential of embryoid bodies as
      chorioallantoic grafts appeared restricted. However, we suggest that the
      accessibility of the chorioallantoic graft can be an advantage for future
      experiments.

PMID- 9551870
TI  - Break-through for calcium antagonists in the treatment of hypertension based on
      the Syst-Eur results.

PMID- 9551871
TI  - Normotensive offspring of hypertensive parents: no evidence of left ventricular
      diastolic dysfunction in a cross-sectional study.
AB  - Left ventricular filling alterations occur early in the development of systemic
      hypertension. We tested the hypothesis that alteration of diastolic filling might
      be present in a normotensive population with increased genetic risk for
      hypertension in the absence of increased left ventricular mass. In a blinded
      study we compared 31 lean, normotensive offspring of hypertensive parents having
      normal left ventricular mass (risk group) with 30 matched individuals without
      family history of hypertension (control group). Left ventricular diastolic
      function was assessed using Doppler echocardiography. Transmitral flow velocities
      showed no significant differences between the two groups. Peak early diastolic
      flow was 0.79+/-0.12 m/s and 0.79+/-0.13 m/s in the risk group and control group,
      respectively. Peak late diastolic flow was 0.44+/-0.08 in the risk group and
      0.42+/-0.11 m/s in the control group. The ratio of early to late diastolic
      velocity was 1.85+/-0.32 and 1.94+/-0.37. The deceleration time of the early
      diastolic flow was identical in both groups: 138+/-24 ms and 138+/-23 ms. There
      was no significant prolongation of the isovolumic relaxation time in the risk
      group: 75+/-17 compared to 73+/-17 ms in the control group. Doppler measurements
      showed no correlation with left ventricular mass. We conclude that, in this cross
      sectional study, young normotensive offspring of hypertensive parents do not
      exhibit Doppler echocardiographic signs of diastolic filling alteration in the
      absence of increased left ventricular mass.

PMID- 9551872
TI  - Gender and the systemic hypertension-snoring association: a questionnaire-based
      case-control study.
AB  - Since the role of gender in the association between hypertension and snoring is
      unknown, we studied it while accounting for age and body mass index (BMI) as
      confounding variables. A questionnaire on snoring was administered to 90
      hypertensive (HT) subjects (45 men and 45 women) and to 90 normotensive (NT)
      subjects matched for gender, age and BMI. As expected, snoring was more commonly
      reported by men than by women, but no significant difference was found between HT
      and NT men, irrespective of age. Conversely, heavy snoring was more frequently
      reported by HT than NT women; habitual snoring was more common among young (age <
      50 years) HT than NT women; and heavy snoring was more common among older (age >
      50 years) HT than NT women. These data suggest an effect of gender on the
      hypertension-snoring association: in men, snoring may be accounted for by age and
      BMI whether or not hypertension is present, whereas in women the natural history
      of snoring appears different and more severe in HT than in NT. Although the
      mechanism(s) responsible for the differences between men and women are obscure at
      present, gender may be an important variable in the systemic hypertension-snoring
      association.

PMID- 9551873
TI  - Adrenomedullin levels are high in primary aldosteronism due to adenoma and
      decline after surgical cure.
AB  - The aim of the study was to evaluate the possible changes in plasma
      adrenomedullin (AM) levels in patients with primary aldosteronism before and
      after surgical resection. The study included 13 patients affected by aldosterone
      producing adenoma (9 women, 4 men; mean age 36.2+/-14.2 years) and 20 healthy
      control subjects (7 women, 13 M; mean age 31.8+/-12.4 years). Unilateral
      adrenalectomy was performed in all patients and adrenal mass consisted of a
      benign adrenal cortical adenoma. The mean plasma AM concentrations in patients
      with primary aldosteronism (36.2+/-19.3 pg/ml) were significantly (p < 0.0001)
      higher than those of normal subjects (13.2+/-6.2 pg/ml). In these patients the
      plasma AM levels significantly (p < 0.0001) reduced after surgical removal of the
      tumours (14.9+/-7.6 pg/ml). In all patients with aldosterone-producing adenoma,
      tumour diameter correlated with the plasma AM concentrations (r=0.631; p <
      0.021). In conclusion, the present investigation shows that in primary
      aldosteronism due to adrenal adenoma plasma AM levels are higher at the moment of
      diagnosis and decline after successful adrenal operation.

PMID- 9551874
TI  - A placebo-controlled comparison of diltiazem and amlodipine monotherapy in
      essential hypertension using 24-h ambulatory monitoring.
AB  - Thirty patients (17 females, median age 55 years) with mild/moderate hypertension
      (sitting diastolic blood pressure 95-110 mmHg over 2 consecutive weeks)
      participated in a study of the efficacy and tolerability of once-daily diltiazem
      "controlled delivery" 180 mg-360 mg and amlodipine 5-10 mg compared with placebo
      (using clinic and 24-h ambulatory blood pressure measurement (Accutraker II). The
      study was conducted in a general practice setting using a randomized double-blind
      crossover design with Latin square allocation of treatment order within subjects.
      During each phase, doses were titrated to achieve a predose clinic sitting
      diastolic blood pressure of 90 mmHg. Three patients withdrew while taking
      amlodipine and 3 while taking placebo. The numbers of patients receiving the
      higher dose in each phase were as follows: placebo 22, diltiazem 12 and
      amlodipine 19. End-of-phase mean clinic sitting blood pressures were as follows:
      placebo 152/100, diltiazem 146/95 and amlodipine 140/93. End-of-phase mean 24-h
      ambulatory blood pressures were as follows: placebo 151/93, diltiazem 143/86 and
      amlodipine 137/84. Both clinic and ambulatory blood pressures were therefore
      significantly reduced (p < 0.01) in both active phases compared with placebo, and
      systolic blood pressure was also significantly lower with amlodipine compared
      with diltiazem. Heart rate was increased with amlodipine. Both drugs were well
      tolerated, and adverse events were predictable for each agent, with amlodipine
      causing more vasodilator side effects. Thus both amlodipine and diltiazem once
      daily are effective in reducing blood pressure. While amlodipine is more potent
      than diltiazem in reducing systolic blood pressure, it causes more vasodilator
      side effects.

PMID- 9551875
TI  - Comparison of the angiotensin II receptor antagonist irbesartan with atenolol for
      treatment of hypertension.
AB  - In this multicenter, double-blind study, the antihypertensive efficacy and safety
      of irbesartan were compared with those of atenolol in patients with mild-to
      moderate hypertension. Following a 4- to 5-week placebo lead-in period, 231
      patients with seated diastolic blood pressure (SeDBP) 95-110 mmHg were randomized
      to irbesartan 75 mg or atenolol 50 mg once daily for 24 weeks. Doses were doubled
      at Week 6 for SeDBP > or = 90 mmHg. At Week 12, or anytime thereafter, doses were
      doubled for SeDBP > or = 90 mmHg if not done at Week 6, and hydrochlorothiazide
      and then nifedipine were added. Efficacy was determined by change from baseline
      in blood pressure and by therapeutic response rates. Safety was assessed by
      monitoring adverse events (AEs). Both treatments significantly lowered blood
      pressure from baseline. There were no significant differences between treatment
      groups with respect to blood pressure changes or therapeutic response. Atenolol
      significantly reduced seated heart rate compared with irbesartan at Week 12. The
      incidences of serious AEs and discontinuations due to AEs were approximately
      twice as high in the atenolol group compared with the irbesartan group. Thus, in
      comparison to atenolol, irbesartan < or = 150 mg provided at least equivalent
      blood pressure control while demonstrating an excellent safety and tolerability
      profile.

PMID- 9551876
TI  - A 5-year comparison of doxazosin and atenolol in patients with mild-to-moderate
      hypertension: effects on blood pressure, serum lipids, and coronary heart disease
      risk.
AB  - The long-term efficacy and safety of once-daily treatment with doxazosin or
      atenolol were compared in a 5-year study in patients with mild-to-moderate
      hypertension. The study consisted of a 1-year, multicenter, double-blind,
      parallel-group phase, followed by a 4-year, open-label extension phase. Of the
      228 patients enrolled, 100 patients (54/111 doxazosin and 46/117 atenolol)
      completed the 5-year study. Both treatments were similarly efficacious in
      controlling blood pressure. As assessed by the Framingham risk equation, which
      incorporates lipid parameter values, patients receiving doxazosin had
      significantly less chance of developing coronary heart disease (CHD) within 10
      years compared with those patients receiving atenolol (p < 0.05). Doxazosin
      significantly (p=0.0005) reduced the mean CHD risk from baseline to final visit
      by 12.3%; whereas, atenolol produced essentially no change in mean risk (0.2%
      increase). In patients receiving doxazosin, statistically significant (p < 0.05)
      increases from baseline were observed in serum concentrations of high-density
      lipoprotein (HDL) cholesterol and the HDL/total cholesterol ratio during the
      first 2 and 3 years of treatment, respectively. In contrast, significant (p <
      0.05) percent reductions from baseline in both these lipid parameters were seen
      in atenolol-treated patients during most of the 5-year trial. Between-group
      differences were statistically significant (p < 0.01) at all time points.
      Decreases in total cholesterol were similar between the two treatment groups.
      Triglycerides, however, significantly increased with atenolol treatment (p <
      0.0001 vs baseline) while remaining essentially unchanged with doxazosin
      treatment. The safety profiles of doxazosin and atenolol were comparable. Thus,
      while demonstrating similar antihypertensive efficacy and safety during this 5
      year study, once-daily treatment with doxazosin produced a significantly greater
      beneficial effect on both 10-year CHD risk and serum lipid parameters compared
      with atenolol.

PMID- 9551878
TI  - The antihypertensive effect and tolerability of candesartan cilexetil, a new
      generation angiotensin II antagonist, in comparison with losartan.
AB  - This multicentre study compared the antihypertensive effect and tolerability of
      the novel angiotensin II antagonist candesartan cilexetil with those of losartan
      and placebo. Men and women aged 20-80 years, with primary hypertension and
      sitting diastolic blood pressure (DBP) 95-114 mm Hg after a 4-week placebo run-in
      period, were randomized to once daily double-blind treatment with candesartan
      cilexetil 8 mg (n=82), candesartan cilexetil 16 mg (n=84), losartan 50 mg (n=83)
      or placebo (n=85) for 8 weeks. Blood pressure was measured 6 and 24 h after dose,
      i.e. at peak and trough. Differences between treatments were analysed by analysis
      of covariance, and the primary effect variable was reduction in trough sitting
      DBP. Compared with placebo treatment, trough DBP was significantly reduced by a
      mean (95% CI) of 8.9 (6.0; 11.8) mm Hg with 8 mg and 10.3 (7.4; 13.2) mm Hg with
      16 mg candesartan cilexetil. The 8 mg dose was as effective as losartan 50 mg,
      while 16 mg candesartan cilexetil was significantly more effective, with a
      difference between treatments of 3.7 (0.8; 6.7) mm Hg (p=0.013). The placebo
      corrected trough/peak ratio was 0.9-1.1 with candesartan cilexetil and 0.7 with
      losartan. Candesartan cilexetil was similarly well tolerated as placebo. In
      conclusion, candesartan cilexetil 8 mg or 16 mg once daily is an effective and
      well tolerated antihypertensive treatment. Candesartan cilexetil 16 mg is
      significantly more effective than losartan 50 mg once daily.

PMID- 9551877
TI  - Relationship between salt and blood pressure in hypertensive patients on chronic
      ACE-inhibition.
AB  - We investigated the effect of a 4-day oral salt load (150 mmol NaCl extra per
      day) on blood pressure, erythrocyte sodium transport and the activity in the
      renin-angiotensin system in six males with primary hypertension, who had attained
      normotension on chronic enalapril treatment for 4 years. The design was a placebo
      controlled, randomized, two-way cross over, double-blind study, i.e. each patient
      served as his own control. Intracellular erythrocyte sodium and potassium content
      were measured by flame photomometry. The increase in the intracellular sodium
      concentration during 1 h in 37 degrees C incubation of whole-blood with ouabain
      (compared with no-ouabain) was measured to determine the rate of active sodium
      efflux. 24-h blood pressure registration was performed with Space-lab equipment
      (SL 90202) before and at the end of the salt load. Left ventricular morphology
      was evaluated with echocardiography and the minimal vascular resistance of the
      hand vascular bed with water plethysmography at baseline and after 4 years on
      enalapril. Four years' enalapril treatment caused a significant decrease in blood
      pressure, left ventricular mass and minimal vascular resistance. During the 4-day
      salt load average 24-h blood pressure was significantly elevated, 129+/-3/85+/-2
      mmHg as compared to 124+/-2/82+/-2 mmHg during placebo treatment (p=0.025). The
      change (delta) in MAP during high salt intake showed a negative relationship to
      delta-sodium efflux rate constant (r=-0.65, p=0.047). No significant relationship
      was found between the blood pressure response to the salt load and structural
      cardiovascular changes. In conclusion, a short-term oral salt load in
      hypertensive patients on chronic enalapril treatment caused a blood pressure
      rise, which was related to cellular sodium transport but not to structural
      cardiovascular changes.

PMID- 9551880
TI  - Imported dracunculiasis--United States, 1995 and 1997.
AB  - Dracunculiasis is a parasitic infection caused by a filarial worm (Dracunculus
      medinensis [i.e., Guinea worm]) that is transmitted through contaminated drinking
      water. Approximately 1 year after a person is infected, one or more meter-long
      adult female worms begin to emerge through the skin, often incapacitating the
      patient for > or =2 months. Despite a dramatic decrease in cases worldwide,
      dracunculiasis is still occasionally imported into the United States. Since 1995,
      two cases of dracunculiasis have been reported in the United States, both
      imported from Sudan. This report summarizes the investigation of these cases.

PMID- 9551879
TI  - Tissue angiotensin II concentration in the heart and kidneys in transgenic
      Tsukuba hypertensive mice.
AB  - Tsukuba hypertensive mice (THM) are transgenic mice carrying both human renin and
      angiotensinogen genes, and possessing an overexpressing human renin-angiotensin
      system. The aim of this study is to evaluate the angiotensin II concentration in
      the heart and kidney in THM. Twenty-week-old male THM and control C57BL/6 mice
      (C57) were used. Each group consisted of 3 mice. For each mouse, systolic blood
      pressure, heart to body weight ratio, renal glomerular sclerosis index and
      angiotensin II concentration in the heart and kidney were measured. Systolic
      blood pressure of THM was about 40 mmHg higher than that of C57. Heart to body
      weight ratio and renal glomerular sclerosis index were significantly higher in
      THM than those in C57. The angiotensin II concentration in THM was about 4 times
      higher in the heart and about 5 times higher in the kidney compared with that in
      C57. These results suggest that accelerated tissue angiotensin II production,
      significant cardiac hypertrophy and renal glomerular sclerosis all occur because
      of hypertension.

PMID- 9551881
TI  - Update: HIV counseling and testing using rapid tests--United States, 1995.
AB  - Approximately 25 million persons each year in the United States are tested for
      antibody to human immunodeficiency virus (HIV). Publicly funded counseling and
      testing (CT) programs conduct approximately 2.5 million of these tests each year.
      CT can have important prevention benefits; however, in 1995, 25% of persons
      testing HIV-positive and 33% of persons testing HIV-negative at publicly funded
      clinics did not return for their test results. Rapid tests to detect HIV antibody
      can be performed in an average of 10 minutes, enabling health-care providers to
      supply definitive negative and preliminary positive results to patients at the
      time of testing, potentially increasing the overall effectiveness of CT. In
      comparison, results from enzyme immunoassays (EIAs) currently used for HIV
      screening often are not available for 1-2 weeks. To quantify the potential
      advantages and disadvantages of using rapid tests for CT, CDC estimated the
      potential impact on the number of persons who would learn their HIV-test results.
      This report summarizes the results of the analysis and provides the basis for
      changing the Public Health Service (PHS) recommendations for providing HIV-test
      results.

PMID- 9551882
TI  - Strategies for providing follow-up and treatment services in the National Breast
      and Cervical Cancer Early Detection Program--United States, 1997.
AB  - The Breast and Cervical Cancer Mortality Prevention Act of 1990 authorized CDC to
      establish the National Breast and Cervical Cancer Early Detection Program
      (NBCCEDP) to increase screening services for women at low income levels who are
      uninsured or underinsured. Although the NBCCEDP covers most diagnostic services
      that women need after receiving an abnormal mammography or Papanicolaou (Pap)
      test result, the program does not reimburse for breast biopsies. In addition, the
      Act prohibits the use of NBCCEDP funds for cancer treatment. Participating health
      agencies must ensure that NBCCEDP clients receive timely, appropriate diagnostic
      and treatment services. In 1996, CDC began a case study to determine how early
      detection programs in seven participating states (California, Michigan,
      Minnesota, New Mexico, New York, North Carolina, and Texas) identified resources
      and obtained diagnostic and treatment services. This report summarizes the
      results of the study, which indicate that respondents in these states reported
      that treatment had been initiated for almost all NBCCEDP clients in whom cancer
      was diagnosed. However, respondents also considered the strategies used to obtain
      these services as short-term solutions that were labor-intensive and diverted
      resources away from screening activities.

PMID- 9551883
TI  - Differential TCR signaling and the generation of memory T cells.
AB  - There are currently two models for the generation of memory T cells: 1) memory T
      cells arise directly from activated effector T cells that have reverted to the
      resting state via an unknown mechanism; and 2) memory T cells are generated
      directly from naive T cells, bypassing an effector stage. I discuss here how
      recent results on the activation and signaling requirements of naive vs memory
      CD4 T cells favor the second model and how differential signaling of naive T
      cells may direct their developmental outcome.

PMID- 9551884
TI  - A critical, invariant chain-independent role for H2-M in antigen presentation.
AB  - Antigen presentation by MHC class II (class II) is facilitated by the accessory
      molecules, invariant chain (Ii) and H2-M. Ii associates with class II during
      biosynthesis and promotes transport of class II to Ag-loading compartments. One
      function of H2-M is the removal of Ii fragments from MHC class II. We have
      previously demonstrated that Ii-deficient mice, unlike class II-deficient mice,
      are resistant to L. major infection. In the present study, we found that H2-M
      deficient (H2-M0) mice were susceptible to progressive infection with L. major.
      The dispensability of Ii for control of L. major allowed genetic analysis of
      whether H2-M functions by association with or independently of Ii. In contrast to
      Ii-deficient (Ii0) mice, Ii0H2-M0 mice were as susceptible to L. major as H2-M0
      mice. Thus, H2-M has an essential, Ii-independent function during presentation of
      microbial pathogens.

PMID- 9551885
TI  - Cytokine-dependent abortion in CBA x DBA/2 mice is mediated by the procoagulant
      fgl2 prothrombinase [correction of prothombinase].
AB  - Spontaneous resorption in the CBA x DBA/2 model is attributed to NK cells,
      macrophages, and Th1-type cytokines. In vivo depletion of NK cells by anti
      asialoGM1 Ab or macrophage depletion by silicon dioxide treatment reduced
      abortion rates, which could no longer be boosted by injecting TNF-alpha (which
      activates NK cells) or IFN-gamma (which activates macrophages). TNF-alpha + gamma
      IFN coadministration aborted >80% of the embryos whether or not NK cells or
      macrophages had been depleted or estradiol + progesterone was injected to correct
      potential reduction in ovarian function by cytokines. The cytokines also aborted
      IRF1+/+ C57BL/6 but not IRF1-/- females pregnant by IRF1+/+ DBA/2. Both
      spontaneous and cytokine-boosted abortions in CBA x DBA/2 were blocked by Ab to
      fgl2 prothrombinase [corrected] expressed by cytokine-stimulated vascular
      endothelial cells and monocytes; in vivo Ab depletion of granulocytes also
      prevented TNF-alpha + IFN-gamma-induced abortions. Cytokine-triggered
      thrombotic/inflammatory processes in maternal uteroplacental blood vessels causes
      abortion.

PMID- 9551886
TI  - T helper 1 and T helper 2 cells respond differentially to chemokines.
AB  - T effector subsets, such as Th1 or Th2 cells, are key players in inflammatory
      reactions. It is not known whether chemokines are able to recruit these subsets
      differentially, as has been shown for memory vs naive T cells. Here we
      demonstrate that Th1 and Th2 cells differ in their intrinsic migratory properties
      and their chemotactic responsiveness toward distinct chemokines. While the CC
      chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES
      were efficient chemoattractants for Th1 cells, inducing a dose-dependent
      transmigration, Th2 cells were not attracted by these chemokines. Another CC
      chemokine, JE/monocyte chemoattractant protein (MCP)-1, and a CXC-chemokine,
      stromal cell-derived factor (SDF)-1alpha, exerted chemotactic effects on both Th1
      and Th2 cells, but differences in sensitivity and the percentage of responding
      cells were recorded between both subsets. These results indicate that chemokines
      play a distinct role in the regulation of local immune reactions by influencing
      the local balance between proinflammatory and antiinflammatory T cell subsets.

PMID- 9551887
TI  - Detection of MCP-4 in dermal fibroblasts and its activation of the respiratory
      burst in human eosinophils.
AB  - CC-chemokines are an important family of proinflammatory mediators that promote
      the recruitment and activation of human eosinophils in chronic inflammatory
      diseases. Recently, a novel human CC-chemokine, monocyte chemotactic protein 4
      (MCP-4), has been reported that shows amino acid sequence similarities with
      eotaxin and RANTES, induces chemotaxis of eosinophils, and signals through
      specific chemokine receptors. In this study, we investigated the effect of MCP-4
      on different eosinophil effector functions leading to the activation of the
      respiratory burst. In human eosinophils, MCP-4 dose dependently induced the
      production of reactive oxygen species and actin polymerization as a related
      event. Pretreatment of eosinophils with different enzyme inhibitors interacting
      with the signal transduction cascade revealed that Gi protein, protein kinase C,
      tyrosine kinase, and phosphatidylinositol-3-kinase are involved in the signaling
      following stimulation with MCP-4. In addition, cytokine-stimulated human dermal
      fibroblasts expressed high levels of MCP-4 mRNA, suggesting that fibroblasts are
      a physiologic source of MCP-4. Therefore, this study demonstrates that there is
      an important role of MCP-4 in the activation of eosinophils and that the
      interaction between dermal fibroblasts and human eosinophils may play an
      important role within the cytokine network.

PMID- 9551888
TI  - Suppression of immune responses by CD8 cells. I. Superantigen-activated CD8 cells
      induce unidirectional Fas-mediated apoptosis of antigen-activated CD4 cells.
AB  - Stimulation of mature CD4 cells through the TCR induces cellular activation and
      expansion that are often followed by clonal elimination by a form of apoptosis
      termed activation-induced cell death. This process of CD4 cell apoptosis is
      generally thought to reflect clonal suicide and to be independent of other cell
      types. Here we show that during the response to the superantigen Staphylococcal
      enterotoxin A, activated CD8 cells, but not activated CD4 cells, suppress the CD4
      proliferative response. Suppression by CD8 cells reflects their ability to induce
      CD4 cell apoptosis via ligation of Fas. Moreover, although activated CD8 cells
      that express Fas ligand and Fas eliminate CD4 cells through a Fas-dependent
      mechanism, they are themselves resistant to Fas-dependent apoptosis. These
      findings indicate a fundamental difference between the two major T cell subsets
      with regard to sensitivity to Fas-dependent apoptosis, expression of Fas ligand,
      and mediation of suppressive activity following immunization with superantigen.

PMID- 9551889
TI  - Suppression of immune responses by CD8 cells. II. Qa-1 on activated B cells
      stimulates CD8 cell suppression of T helper 2 responses.
AB  - We have investigated the role of MHC class I products and CD8 T cells in
      regulating Ab responses using beta2-microglobulin deficient (beta2m-/-) mice.
      Beta2m-/- mice produced stronger IgM and IgG responses than did control beta2m+/+
      mice to both cellular and viral Ags. These Ab responses could be suppressed by
      infusion of activated B cells from beta2m+/+ mice. Further investigation showed
      that the beta2m-associated molecule on activated B cells that induced CD8
      suppression was Qa-1 and that the Th2 component of CD4 cells was most affected by
      CD8-suppressive activity. Our findings suggest a novel pathway of Th inhibition
      in which B cell presentation of Qa-1-associated peptides stimulates CD8
      suppressive activity.

PMID- 9551890
TI  - Rejection of allogeneic and syngeneic but not MHC class I-deficient tumor grafts
      by MHC class I-deficient mice.
AB  - The ability of TAP1-/-, beta2m-/-, and TAP1/beta2m-/- mice to mount rejection
      responses against allogeneic, syngeneic, and MHC class I-deficient tumor grafts
      was examined. The results demonstrate a potent ability of TAP1-/- and beta2m-/-
      as well as TAP1/beta2m-/- mice to reject allogeneic tumors. In contrast to
      published data, rejection of syngeneic MHC class I-expressing tumors was also
      observed. This response was specific for the MHC class I-deficient mice, since
      wild-type mice did not reject syngeneic MHC class I-positive tumors under
      identical experimental conditions. The rejection response of syngeneic tumors
      required preimmunization of the mice and was MHC class I specific at the level of
      priming as well as at the level of the tumor target. Finally, MHC class I
      deficient tumor grafts were accepted in MHC class I-deficient mice while similar
      grafts were rejected in wild-type mice. In summary, while MHC class I-deficient
      mice have retained a capacity to reject allogeneic tumors. they have gained an
      ability to reject syngeneic MHC class I-positive tumors and lost the ability to
      reject MHC class I-negative tumors. The present results are discussed in relation
      to the role of MHC class I molecules in selecting functional CD8+ T and NK cell
      repertoires, and the development of cell-mediated immunity.

PMID- 9551891
TI  - Ovalbumin-specific, MHC class I-restricted, alpha beta-positive, Tc1 and Tc0 CD8+
      T cell clones mediate the in vivo inhibition of rat IgE.
AB  - In the following study, we demonstrate that medium responder PVG rats immunized
      i.p. with OVA complexed to the adjuvant aluminum hydroxide exhibit a moderate IgE
      response (400-1000 ng/ml). In these rats, we demonstrate that underlying the MHC
      class II-restricted CD4+ T cell response, there is an MHC class I-restricted CD8+
      T cell component that plays an important role in restricting the magnitude and
      duration of the IgE response. We show that in vivo depletion of CD8+ T cells
      effects a massive increase in IgE (20-fold), and that they are MHC class I
      restricted, OVA-specific, cytolytic cells that universally produce IFN-gamma (25
      69 ng/ml) and IL-2 (7.6-22 U/ml), and occasionally secrete IL-4 (68-81 U/ml IL
      4), and when adoptively transferred into CD8-depleted recipients, can effect a
      significant reduction in IgE (3- to 50-fold). We also demonstrate that this in
      vivo inhibition of IgE is dependent on the Ag-specific activation of the CD8+ T
      cells, and that the activated CD8+ T cells will suppress total/bystander IgE in
      an Ag-nonspecific manner. These data are consistent with a growing literature
      demonstrating sensitization of MHC class I-restricted CD8+ T cells by exogenous
      protein Ags delivered to mucosal sites, and may represent a mechanism whereby a
      selective pressure can be applied on the functional outcome of an immunoglobulin
      response to environmental allergens.

PMID- 9551892
TI  - Reduced T helper 1 responses in IL-12 p40 transgenic mice.
AB  - To investigate the antagonistic effect of IL-12 p40 on IL-12 activity in vivo, we
      generated transgenic (Tg) mice in which p40 gene was regulated by a liver
      specific promoter. Three Tg mouse lines were generated, and they expressed the
      p40 transgene predominantly in liver. Serum p40 level was extremely high, and it
      consisted of mainly monomer and homodimer and also of higher m.w. complexes.
      These Tg mice did not show any apparent phenotypic difference from control
      littermates in lymphoid cells. Enhancement of NK cell lytic activity in spleen by
      administration of rIL-12 to these mice was greatly diminished. Ag induced
      cytokine production was impaired: decreased production of IFN-gamma and increased
      production of IL-4 and IL-10. Delayed-type hypersensitivity response was also
      significantly reduced. Moreover, these Tg mice showed increased susceptibility to
      the infection with an intracellular pathogen, blood-stage Plasmodium berghei XAT,
      which is an irradiation-induced attenuated substrain of P. berghei NK65,
      presumably due to the decreased IFN-gamma production. These results suggest that
      p40 functions as an IL-12 antagonist in vivo, and that Th1 responses in p40 Tg
      mice are significantly reduced. Thus, these Tg mice could be a useful model to
      evaluate the inhibitory effect of p40 on IL-12-mediated various immune responses
      in vivo.

PMID- 9551893
TI  - CD40 ligand exerts differential effects on the expression of I gamma transcripts
      in subclones of an IgM+ human B cell lymphoma line.
AB  - The CD40:CD40 ligand (CD40L) interaction plays a critical role in T cell
      dependent isotype switching. To elucidate the role of CD40 signaling in the
      activation of gamma germline transcription and as an extension, in targeting
      Cgamma regions for isotype switching, an IgM+ Burkitt lymphoma cell line (Ramos
      2G6) was assayed for the up-regulation of germline gamma transcripts after CD40L
      stimulation. Independent Ramos 2G6 subclones that either expressed (Igamma+) or
      did not express (Igamma-) basal levels of Igamma transcripts were assessed for
      their transcriptional response to CD40L signaling by contact with either a Jurkat
      T cell line (D1.1) or a transfected CD40L-expressing epithelial cell line
      (293/CD40L) in the presence or absence of IL-4. Both Igamma- and Igamma+ Ramos
      2G6 subclones cultured with IL-4 and CD40L markedly up-regulated germline
      transcription predominantly from the gamma1, gamma2, and gamma3 subclasses over
      levels obtained with IL-4 alone. In addition, these two signals were required to
      obtain de novo switch recombination. However, incubation with CD40L alone
      resulted in a substantial increase in germline transcription only in the Igamma+
      and not the Igamma- subclones. Observed basal transcription at the gamma1 locus
      also correlated with the ability of not only the gamma1 locus, but also the
      gamma2 and gamma3 loci, to up-regulate germline transcripts in response to CD40
      signaling. These data are consistent with CD40:CD40L contact up-regulating
      germline transcription only after the B cell has received a signal that alters
      the transcriptional state of the heavy chain locus.

PMID- 9551894
TI  - MHC class II expression in double mutant mice lacking invariant chain and DM
      functions.
AB  - Invariant (Ii) chain and DM functions are required at distinct stages during
      class II maturation to promote occupancy by diverse peptide ligands. The class II
      molecules expressed by mutant mouse strains lacking Ii chain or DM activities
      display discrete structural and functional abnormalities. The present report
      describes the cellular and biochemical characteristics of Ii-DM- doubly deficient
      mice. As for Ii chain mutants, their mature Aalphab Abetab dimers similarly
      exhibit reduced mobilities in SDS-PAGE, and in functional assays these molecules
      behave as if empty or occupied by an easily displaced peptide. Additionally, the
      present experiments demonstrate that the production of floppy Aalphab Abetab
      dimers is TAP independent. In comparison with Ii chain mutants, Ii-DM- doubly
      deficient cell populations exhibit increased peptide binding activities and
      consistently greater presentation abilities in T cell stimulation assays. These
      functional differences appear to reflect higher class II surface expression
      associated with their increased representation of B lymphocytes. We also observe
      defective B cell maturation in mice lacking Ii chain or DM expression, and
      interestingly, B cell development appears more severely compromised in Ii-DM-
      double mutants. These mutant mice lacking both Ii chain and DM activities should
      prove useful for analyzing nonconventional class II Ag presentation under normal
      physiological conditions in the intact animal.

PMID- 9551895
TI  - Intercellular adhesion molecule-1 and leukocyte function-associated antigen-3
      provide costimulation for superantigen-induced T lymphocyte proliferation in the
      absence of a specific presenting molecule.
AB  - Bacterial superantigens can bind TCR in the absence of MHC class II molecules and
      activate T lymphocytes when cocultured with certain class II-deficient accessory
      cells. It has not been determined, however, whether these accessory cells provide
      direct costimulation to the T cell or serve to present superantigens via a
      nonconventional ligand. We have identified a human adenocarcinoma cell line,
      SW480, that assists in the activation of human T cells by the staphylococcal
      enterotoxins B (SEB), C1 (SEC1), and D (SED), but not SEA, SEC2, SEC3, or SEE.
      SW480 cells did not express class II molecules, and anti-class II mAbs did not
      inhibit T cell proliferation, supporting the hypothesis that class II is not
      absolutely required for enterotoxin-mediated T cell activation. The TCR Vbeta
      profile of T cells stimulated by SEB plus SW480 cells was similar to that of T
      cells stimulated by SEB plus class II+ APC, indicating that TCR-SEB interactions
      were preserved in the absence of class II molecules. Binding studies failed to
      detect specific association of SEB with SW480 cells, suggesting that SW480 cells
      do not express receptors for enterotoxin. SEB coupled to beads, however,
      stimulated T cell proliferation, but only in the presence of SW480 cells. SW480
      cells express both ICAM-1 and LFA-3 molecules, and the addition of Abs to these
      receptors inhibited T cell proliferation. These findings support a model in which
      certain enterotoxins engage the TCR independent of MHC class II or other specific
      presenting molecules and induce T cell proliferation with signals provided by
      nonconventional accessory cells.

PMID- 9551896
TI  - Blockade of chemokine activity by a soluble chemokine binding protein from
      vaccinia virus.
AB  - Chemokines direct migration of immune cells into sites of inflammation and
      infection. Chemokine receptors are seven-transmembrane domain proteins that, in
      contrast to other cytokine receptors, cannot be easily engineered as soluble
      chemokine inhibitors. Poxviruses encode several soluble cytokine receptors to
      evade immune surveillance, providing new strategies for immune modulation. Here
      we show that vaccinia virus and other orthopoxviruses (cowpox and camelpox)
      express a secreted 35-kDa chemokine binding protein (vCKBP) with no sequence
      similarity to known cellular chemokine receptors. The vCKBP binds CC, but not CXC
      or C, chemokines with high affinity (Kd = 0.1-15 nM for different CC chemokines),
      blocks the interaction of chemokines with cellular receptors, and inhibits
      chemokine-induced elevation of intracellular calcium levels and cell migration in
      vitro, thus representing a soluble inhibitor that binds and sequesters
      chemokines. The potential of vCKBP as a therapeutic agent in vivo was illustrated
      in a guinea pig skin model by the blockade of eotaxin-induced eosinophil
      infiltration. a feature of allergic inflammatory reactions. Furthermore, vCKBP
      may enable the rational design of antagonists to neutralize pathogens that use
      chemokine receptors to initiate infection, such as HIV or the malarial parasite.

PMID- 9551897
TI  - The level of CD4 surface protein influences T cell selection in the thymus.
AB  - During T cell development thymocytes are subjected to positive and negative
      selection criteria to ensure that the mature T cell repertoire is MHC restricted,
      yet self tolerant at the same time. The CD4 and CD8 coreceptors are thought to
      play a crucial role in this developmental process. To elucidate the role of CD4
      in T cell selection, we have produced a mouse strain that expresses CD4 at a
      reduced level. We used homologous recombination in embryonic stem cells to insert
      neo into the 3' untranslated region of CD4. The resulting mice have a reduction
      in the percentage of CD4+ cells in the thymus and a concomitant increase in CD8+
      cells. In addition, breeding two individual class II-restricted TCR transgenic
      mice onto the CD4low (low level of CD4) mutant background affects the selection
      of each TCR differentially. In one case (AND TCR transgenic), significantly fewer
      CD4+ cells with the transgenic TCR develop on the CD4low mutant background,
      whereas in the other (5C.C7 TCR transgenic), selection to the CD4 lineage is only
      slightly reduced. These data support the differential avidity model of positive
      and negative selection. With little or no avidity, the cell succumbs to
      programmed cell death, low to moderate avidity leads to positive selection, and
      an avidity above a certain threshold, presumably above one that would lead to
      autoreactivity in the periphery results in clonal deletion. These data also
      support the idea that a minimum avidity threshold for selection exists and that
      CD4 plays a crucial role in determining this avidity.

PMID- 9551899
TI  - Perforin protects against autoimmunity in lupus-prone mice.
AB  - The roles of cytolytic regulatory mechanisms in the immune system of lupus-prone
      mice were examined in perforin-deficient animals bearing functional or defective
      (lpr) Fas Ag (CD95). Perforin-deficient Fas+ animals developed accelerated
      autoimmunity, characterized by increased hypergammaglobulinemia, autoantibody
      production, and immune deposit-related end-organ disease compared with perforin
      intact counterparts. In comparison, perforin-deficient lpr animals had
      accelerated mortality compared with perforin-intact lpr mice, associated with the
      abnormal accumulation of CD3+CD4-CD8- alphabeta T cells in conjunction with
      unaltered hypergammaglobulinemia, autoantibody production, and immune complex
      renal disease. These results indicate that cytolytic lymphoid regulation plays
      critical roles in the immune homeostasis of lupus-prone animals, and identify
      perforin-mediated cytotoxicity as a specific mechanism in the regulation of
      systemic autoimmunity.

PMID- 9551898
TI  - Activation of low avidity CTL specific for a self epitope results in tumor
      rejection but not autoimmunity.
AB  - To determine how self-tolerance can alter the ability of the immune system to
      respond against tumor-associated Ags that are also expressed by normal tissue, we
      designed experiments in which the same protein was expressed both as a tumor Ag
      and as a transgene product. Unlike conventional BALB/c mice that rejected renal
      carcinoma cells transfected with the influenza virus hemagglutinin (Renca-HA),
      transgenic mice that are tolerant of HA due to its expression as a self-Ag on
      pancreatic islet beta cells, (Ins-HA mice) supported progressive growth of these
      tumor cells. However, when Ins-HA mice were immunized with a recombinant strain
      of vaccinia virus expressing the dominant H-2Kd peptide epitope of HA before
      receiving Renca-HA cells, they too were able to reject the tumor cells. Rejection
      of Renca-HA cells by immunized Ins-HA mice was found to be associated with the
      generation of CTL having much lower avidity for target cells presenting the KdHA
      epitope than CTL from immunized conventional BALB/c mice. Significantly, we show
      that self-tolerance to the HA Ag is quantitative rather then absolute, and that
      vaccination of Ins-HA mice can activate low avidity KdHA-specific CD8+ T cells
      that are able to reject tumor cells expressing high levels of HA, yet these mice
      remain tolerant of pancreatic islet beta cells expressing HA.

PMID- 9551900
TI  - MHC class II-transfected tumor cells directly present antigen to tumor-specific
      CD4+ T lymphocytes.
AB  - We have developed and shown to be efficacious an immunotherapeutic strategy to
      enhance the generation of tumor-specific CD4+ T helper lymphocytes. The approach
      uses autologous tumor cells genetically modified to express syngeneic MHC class
      II genes as cell-based immunogens and is based on the hypothesis that tumor cells
      directly present tumor Ags to CD4+ T cells. Since the conventional pathway for
      CD4+ T cell activation is indirect via professional APC, induction of immunity
      following immunization with class II-transfected tumor cells was examined in bone
      marrow chimeric mice. Both tumor and host-derived cells are APC for tumor Ags,
      suggesting that the efficacy of tumor cell vaccines can be significantly improved
      by genetic modifications that enhance tumor cell Ag presentation.

PMID- 9551901
TI  - Induction of tyrosine phosphorylation in human MHC class II-positive antigen
      presenting cells by stimulation with contact sensitizers.
AB  - To investigate the intracellular signaling mechanisms involved in the activation
      of APC by contact sensitizers, we studied the induction of tyrosine
      phosphorylation by these agents. Selective analysis of phosphotyrosine (p-tyr) in
      human Langerhans cells and different mononuclear cell types was achieved using a
      multicolor flow-cytometric technique. Stimulation with contact sensitizers
      revealed a distinct increase in p-tyr exclusively for MHC class II-positive
      cells. For different haptens, irritants, as well as activators of distinct signal
      transduction pathways, it was demonstrated that only strong sensitizers or the
      protein tyrosine phosphatase inhibitor sodium orthovanadate or cross-linking of
      MHC class II molecules were able to induce formation of p-tyr in human blood
      derived dendritic cells serving as model for the dendritic cell family. This
      event required physiologic cell culture conditions and was blocked by specific
      inhibitors of protein tyrosine kinases. No evidence for the inhibition of protein
      tyrosine phosphatases by haptens was found. Western blot analysis of monocyte
      enriched populations revealed an augmented phosphorylation of distinct proteins
      after hapten stimulation partly resembling the pattern noticed after cross
      linking of HLA-DR molecules. In dendritic cells generated from mononuclear
      progenitors, the protein tyrosine kinase inhibitor genistein was able to block
      tyrosine phosphorylation as well as production of IL-1beta mRNA transcripts. Our
      data underline the unique capacity of haptens to activate APC and the important
      role of tyrosine phosphorylation for this process.

PMID- 9551902
TI  - NK cells from human MHC class I (HLA-B) transgenic mice do not mediate hybrid
      resistance killing against parental nontransgenic cells.
AB  - We have investigated the capacity of human MHC class I HLA-B gene products, HLA
      B27, -B7 (fully human), and -B7kb (human-mouse hybrid consisting of the alpha1
      and alpha2 domains of HLA-B7, and the alpha3 and cytoplasmic domains of mouse H
      2Kb), expressed on mouse NK cells during ontogeny to influence NK recognition of
      otherwise syngeneic mouse target cells. Despite a high level of surface
      expression of the transgene (comparable to that of endogeneous H-2DbKb
      molecules), the direct killing of YAC-1 targets, and the killing of P815 targets
      in a redirected lysis assay, the NK effectors of these transgenic mice could not
      mediate hybrid resistance-like killing of nontransgenic C57BL/6 target cells
      either in vitro or in vivo. Splenocytes from B6-B27 mice could be used to
      generate CTL lines against a B27-binding peptide, implying that T cells
      restricted by HLA-B27 developed during ontogeny. NK cells from B6-B27 could lyse
      B6-B27 Con A lymphoblasts pulsed with Db-binding peptide but not B27-binding
      peptides. Taken together, our results show that these human HLA-B transgene
      products cannot function as class I MHC "self" elements for mouse NK cells, even
      when present throughout ontogeny.

PMID- 9551903
TI  - Molecular and genetic requirements for preferential recruitment of TCRBV8S2+ T
      cells in Lewis rat experimental autoimmune encephalomyelitis.
AB  - The underlying mechanisms behind the preferential expression of select TCRBV
      products in certain autoimmune illnesses, such as multiple sclerosis and some
      models of experimental autoimmune encephalomyelitis (EAE), have principally
      remained enigmatic. In this study, we examined the mutual role of nonself- vs
      self-origin of antigenic myelin basic protein (MBP) peptides and given MHC
      haplotypes in relation to the relative frequency of activated TCRBV8S2+ T
      lymphocytes in the Lewis (LEW) rat EAE model. Inbred MHC (RT1) congenic LEW rats
      (LEW (RT1l), LEW.1AV1 (RT1av1), and LEW.1W (RT1u)) were immunized with the 63 to
      88 peptide of the guinea pig MBP (MBPGP63-88). Additionally, LEW rats were
      immunized with the corresponding autologous rat sequence (MBPRAT63-88). Although
      EAE ensued in all MBP peptide/LEW rat strain combinations, only LEW rats
      immunized with the heterologous MBPGP63-88 peptide elicited T cell responses
      encompassing a bias toward TCRBV8S2 expression, as determined by flow cytometric
      analyses. Reduction of TCRBV8S2+ T cells led to mitigation of disease severity in
      LEW rats immunized with MBPGP63-88, but not with MBPRAT63-88, indicating that
      critical encephalitogenic characteristics are associated with this T cell subset.
      We conclude that the preferential recruitment of TCRBV8S2+ T cells in the LEW rat
      EAE model is due to selective, high-avidity recognition of the nonself-MBPGP63-88
      in the context of the RT1.Bl molecule. This inference lends support to the notion
      that the highly restricted TCR repertoire of the self-MBP-reactive T cells in
      certain genetically predisposed multiple sclerosis patients may have its source
      in a multistep molecular mimicry event.

PMID- 9551904
TI  - Adenovector-mediated expression of human thrombopoietin cDNA in immune
      compromised mice: insights into the pathophysiology of osteomyelofibrosis.
AB  - Thrombopoietin (TPO) cDNA can be effectively delivered in vivo by adenovectors.
      Immune normal mice (BALB/c) and syngeneic mice with variable degrees of immune
      dysfunction nu, SCID, and NOD-SCID) were treated with an adenovirus vector
      expressing the human TPO cDNA (AdTPO). Platelet peaks were significantly higher
      in SCID and NOD-SCID mice compared with BALB/c and nu mice. Human plasma TPO
      concentration correlated with the platelet counts. SCID and NOD-SCID mice
      exhibited also granulocytosis and increased numbers of hemopoietic progenitors in
      bone marrow. Following platelet peak, BALB/c mice developed autoantibodies
      against murine TPO leading to thrombocytopenia and depletion of megakaryocytes
      and hemopoietic progenitors in bone marrow. AdTPO-treated SCID mice developed
      osteomyelofibrosis and extramedullary/extrasplenal hemopoiesis. In contrast, NOD
      SCID mice with a similar magnitude of TPO overexpression did not show fibrotic
      changes in bone marrow. We conclude, first, that a chronic high level of TPO
      overexpression stimulates megakaryocytopoiesis and myelopoiesis leading to
      thrombocytosis and granulocytosis. Second, increased megakaryocytopoiesis is not
      sufficient for development of secondary osteomyelofibrosis. The functionally
      deficient monocytes and macrophages of NOD-SCID mice probably prevented fibrotic
      marrow changes. Third, immune deficiency enhances expression of adenovirally
      mediated transgenes, and fourth, xenogeneic transgene delivered by adenovector to
      a host with normal immune functions may induce loss of immune tolerance and
      autoimmune phenomenon.

PMID- 9551905
TI  - Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to
      equivalent triggering signals: correlation with thymic expression of a truncated
      CD8 alpha chain in mice but not rats.
AB  - Unselected CD4+8+ rat thymocytes, generated in vitro from their direct
      precursors, are readily converted to functional TCRhigh T cells by stimulation
      with immobilized TCR-specific mAb plus IL-2. Lineage decision invariably occurs
      toward CD4-8+, regardless of the timing of TCR stimulation after entry into the
      CD4+8+ compartment or the concentration of TCR-specific mAb used for stimulation.
      CD4-specific mAb synergizes with suboptimal TCR-specific mAb in inducing T cell
      maturation, but lineage decision remains exclusively CD4-8+. These results
      contrast with those obtained in mice, in which Abs to the TCR complex were shown
      to promote CD4+8- T cell maturation from CD4+8+ thymocytes. Surprisingly, when
      rat and mouse CD4+8+ thymocytes were stimulated with PMA/ionomycin under
      identical conditions, the opposite lineage commitment was observed, i.e., mouse
      thymocytes responded with the generation of CD4+8- and rat thymocytes with the
      generation of CD4-8+ cells. It thus seems that CD4+8+ thymocytes of the two
      species respond with opposite lineage decisions to strong activating signals such
      as given by TCR-specific mAb or PMA/ionomycin. A possible key to this difference
      lies in the availability of p56lck for coreceptor. supported signaling. We show
      that in contrast to mouse CD4+8+ thymocytes, which express both a complete and a
      truncated CD8 alpha-chain (CD8 alpha') unable to bind p56lck, rat thymocytes only
      express full-length CD8 alpha molecules. Mice, but not rats, therefore may use
      CD8 alpha' as a "dominant negative" coreceptor chain to attenuate the CD8 signal,
      thereby facilitating MHC class II recognition through the higher amount of p56lck
      delivered, and rats may use a different mechanism for MHC class distinction
      during positive selection.

PMID- 9551906
TI  - Three populations of mouse lymph node dendritic cells with different origins and
      dynamics.
AB  - We have identified three distinct populations of mouse lymph node dendritic cells
      (DC) that differ in their capacity to uptake Ag delivered by different routes,
      and in their dynamics. The "I-DCs" are large cells that resemble the
      interdigitating cells and have a mature phenotype and a slow turnover. They
      derive from the regional tissues. The "sm-DCs" and "sI-DCs" are smaller (hence s
      DC), have a more immature phenotype and a rapid turnover. The sI-DC phenotype,
      including CD8alpha expression suggests a lymphoid-related origin. The sI-DC
      population is expanded 100-fold after an in vivo flt3 ligand treatment. The sm-DC
      phenotype suggests a myeloid-related origin. Interestingly, sm-DCs can acquire
      i.v. injected macromolecules in less than 30 min after injection. They may,
      therefore, play an important role in the immune response against blood Ags.

PMID- 9551907
TI  - Positive selection of thymocytes expressing the same TCR by different MHC ligands
      results in the production of functionally distinct thymocytes distinguished by
      differential expression of the heat stable antigen.
AB  - The issue of whether the signaling process during positive selection can affect
      the efficiency by which the positively selected T cells respond to antigenic
      stimulation has not been addressed. We approached this question by determining
      the consequences of positive selection of a particular transgenic TCR (2C TCR) in
      the H-2b and the H-2k thymus. The H-2b thymus provides a strong positive
      selecting environment for the 2C TCR, whereas the H-2k thymus selects weakly for
      the 2C TCR. Although the positively selected CD8 thymocytes from the H-2b or H-2k
      thymus expressed similar levels of the CD8 coreceptor molecule, those for the H
      2k thymus expressed a slightly lower level of the 2C TCR. This lower level of 2C
      TCR expression by H-2k CD8 thymocytes was not a result of coexpression of
      endogenous TCRs. Interestingly, CD8 thymocytes from H-2k mice were hyporesponsive
      to Ag stimulation compared with those from the H-2b mice. The functional maturity
      of positively selected CD8 thymocytes from the H-2b or H-2k thymus was inversely
      correlated with the level of heat stable Ag expressed by these cells.
      Furthermore, TCR-derived signals appear to be more efficiently coupled to
      downstream pathways leading to proliferation and cytokine production in CD8
      thymocytes from H-2b 2C mice than those derived from H-2k 2C mice. These results
      provide the first demonstration that the intensity of the signaling process
      during positive selection affects the efficiency by which TCR-derived signals in
      positively selected thymocytes are coupled to downstream effector pathways.

PMID- 9551908
TI  - A periarteriolar lymphoid sheath-associated B cell focus response is not observed
      during the development of the anti-arsonate germinal center reaction.
AB  - The behavior of p-azophenylarsonate (Ars)-specific B cell clones during the
      primary T cell-dependent splenic response of A/J mice was investigated using an
      immunohistochemical approach. The earliest Ars-specific B cells were observed as
      isolated cells in the red pulp by day 3 after immunization with Ars-keyhole
      limpet hemocyanin, (KLH) and at day 6, large clusters of Ars-specific B cells
      were first detected in germinal centers, which continued to be observed for an
      additional 8 to 15 days. Surprisingly, no Ars-specific B cell foci were observed
      in or near the CD4 T cell-rich periarteriolar lymphoid sheath (PALS) during the
      entire primary response. Nevertheless, A/J mice immunized with (4-hydroxy-3
      nitrophenyl)acetyl-chicken gamma globulin (NP-CGG) or Ars-CGG mounted robust
      splenic (4-hydroxy-3-nitrophenyl)acetyl or CGG-specific PALS-associated focus
      reactions, respectively. In contrast, no Ars-specific PALS B cell foci were
      detected in A/J mice immunized with Ars-CGG. These data add to a growing body of
      evidence indicating that B cell proliferation and differentiation in CD4 T cell
      rich microenvironments are not prerequisites for the GC reaction. Taken together
      with previous results obtained using other model Ags, the data suggest that the
      specificity of the B cell Ag receptor may strongly influence the lymphoid
      microenvironment in which a B cell clone first undergoes Ag-driven clonal
      expansion and differentiation.

PMID- 9551909
TI  - Aberrant intermolecular disulfide bonding in a mutant HLA-DM molecule:
      implications for assembly, maturation, and function.
AB  - HLA-DM (abbreviated DM) is an MHC-encoded glycoprotein that catalyzes the
      selective release of peptides, including class II-associated invariant chain
      peptides, from MHC class II molecules. To perform its function, DM must assemble
      in the endoplasmic reticulum (ER), travel to endosomes, and interact productively
      with class II molecules. We have described previously an EBV-transformed B cell
      line, 7.12.6, which displays a partial Ag presentation defect and expresses a
      mutated DM beta-chain with Cys79 replaced by Tyr. In this study, we show that HLA
      DR molecules in 7.12.6 have a defect in peptide loading and accumulate class II
      associated invariant chain peptides (CLIP). Peptide loading is restored by
      transfection of wild-type DMB. The mutant DM molecules exit the ER slowly and are
      degraded rapidly, resulting in greatly reduced levels of mutant DM in post-Golgi
      compartments. Whereas wild-type DM forms noncovalent alphabeta dimers, such
      dimers form inefficiently in 7.12.6; many mutant DM beta-chains instead form a
      disulfide-bonded dimer with DM alpha. Homodimers of DM beta are also detected in
      7.12.6 and in the alpha-chain defective mutant, 2.2.93. We conclude that during
      folding of wild-type DM, the native conformation is stabilized by a conserved
      disulfide bond involving Cys79beta and by noncovalent contacts with DM alpha.
      Without these interactions, DM beta can form malfolded structures containing
      interchain disulfide bonds; malfolding is correlated with ER retention and
      accelerated degradation.

PMID- 9551910
TI  - Lack of local suppression in orally tolerant CD8-deficient mice reveals a
      critical regulatory role of CD8+ T cells in the normal gut mucosa.
AB  - We found that feeding keyhole limpet hemocyanin (KLH) to CD8-deficient (CD8-/-)
      mice induced oral tolerance that was comparable in both magnitude and quality to
      that induced in wild-type (wt) mice. The tolerance was dose dependent, and only
      higher doses of KLH caused significant reduction in specific Ab and T cell
      responses. Both Th1 and Th2 CD4+ T cell functions were affected. Feeding KLH
      together with cholera toxin (CT) adjuvant, however, abrogated the induction of
      oral tolerance equally well in CD8-/- and wt mice. On the contrary, CT adjuvant
      was unable to abrogate already established oral tolerance in both CD8-/- and wt
      mice. Most importantly, whereas Ag feeding induced hyporesponsiveness in systemic
      as well as in local gut IgA responses in wt mice, a lack of local suppression was
      evident in orally tolerant CD8-/- mice following oral immunizations. Thus,
      contrary to the situation in wt mice, Ag feeding induces systemic, but not local,
      gut IgA hyporesponsiveness in CD8-/- mice, suggesting that CD8+ T cells in the
      normal gut mucosa exert an important down-regulatory function. In wt mice the
      local suppression extended to an unrelated Ag, OVA, given together with KLH and
      CT adjuvant, i.e., bystander suppression. Based on these results we propose that
      tolerance induced by feeding Ag is highly compartmentalized, requiring CD8+ T
      cells for local suppression of IgA responses, whereas systemic tolerance may
      affect CD4+ T cells of both Th1 and Th2 types independently of CD8+ T cells.
      Finally, the adjuvant effect of CT abrogates induction, but not established, oral
      tolerance through a mechanism that does not require CD8+ T cells.

PMID- 9551911
TI  - T cell growth cytokines cause the superinduction of molecules mediating antigen
      induced T lymphocyte death.
AB  - TCR stimulation of T lymphocytes that are activated and cycling in the presence
      of IL-2 leads to programmed cell death. We now show that this effect is at least
      partly attributable to the ability of IL-2 to dramatically increase the
      expression of mRNAs encoding ligands and receptors that mediate apoptosis. We
      also found that cyclosporin was not able to fully inhibit the TCR induction of
      death molecule mRNAs or TCR-induced apoptosis, although it could completely turn
      off IL-2 expression. The effect growth cytokines was further explored in T cells
      derived from mice bearing a homozygous deficiency of the IL-2R alpha-chain. We
      found that IL-2Ralpha-/- cells were resistant to death if IL-2 was used to induce
      apoptosis susceptibility, but that large amounts of other T cell growth
      cytokines, such as IL-4 and IL-7, could induce cell cycle progression and promote
      TCR-induced apoptosis. However, our findings suggest that autoimmunity and
      lymphoproliferation in IL-2Ralpha-/- mice can result from the loss of IL-2
      stimulated feedback apoptosis and that other growth cytokines are not produced at
      levels sufficient to compensate for this deficit.

PMID- 9551913
TI  - Presence of activated antigen-binding B cells during immunization enhances
      relative levels of IFN-gamma in T cell responses.
AB  - To examine the influence of Ag presentation by B cells on immune responses, we
      have used mice transgenic for an Ig heavy chain from a monoclonal anti
      azobenzenearsonate (Ars) Ab to deliver Ag to B cells during immunization. A large
      proportion of transgene-expressing B cells in these mice binds Ars, while
      transgenic serum Ig shows poor Ars binding. Transgenic B cells present Ars
      proteins better than their nonhaptenated counterparts. This is associated with an
      increase in the proliferative responses of transgenic T cells to Ars protein
      immunization. Although B cell numbers in the transgenic mice are lower, many B
      cells in them show an activated phenotype, as identified by altered surface
      levels of peanut agglutinin reactivity, CD23, CD24, CD44, CD62L, and CD86. Even
      against nonhaptenated immunogens, transgenic responses show significant
      enhancement in the relative proportions of the Th1 cytokine IFN-gamma over the
      Th2 cytokines IL-4 and IL-10. Haptenated immunogens further enhance the
      predilection of transgenic mice to produce relatively more IFN-gamma. Consistent
      with this, there is an increase in IgG2a/IgG1 ratios in serum Abs in response to
      haptenated immunogens in transgenic mice. Adoptive transfer of primed hapten
      specific secondary B cells into nontransgenic mice also induces an increase in
      relative levels of IFN-gamma in response to haptenated immunogens. Thus,
      presentation of immunogen in vivo by activated Ag-binding B cells contributes to
      enhanced immunogenicity and a Th1 cytokine bias.

PMID- 9551912
TI  - TGF-beta 1 induces the cyclin-dependent kinase inhibitor p27Kip1 mRNA and protein
      in murine B cells.
AB  - TGF-beta1 inhibits the cell cycle progression of many types of cells by arresting
      them in the G1 phase. This cell cycle arrest has been attributed to the
      regulatory effects of TGF-beta1 on both the levels and the activities of the G1
      cyclins and their kinase partners. The activities of these kinases are negatively
      regulated by a number of proteins, such as p15INK4b, p21WAF1/Cip1, and p27Kip1,
      that physically associate with cyclins, cyclin-dependent kinases (Cdk), or cyclin
      Cdk complexes. In epithelial cell lines, TGF-beta1 was previously shown to
      inhibit cell cycle progression through down-regulation of Cdk4 and/or up
      regulation of p15INK4b and/or p21WAF1/Cip1. However, TGF-beta1 had little or no
      effect on the p27Kip1 mRNA and protein levels. In this report, we show that, in
      contrast to observations in epithelial cell lines, TGF-beta1 increased the
      p27Kip1 mRNA and protein levels in the murine B cell lines CH31 and WEHI231. This
      TGF-beta1-mediated induction of p27Kip1 also resulted in an increased association
      of p27Kip1 with Cdk2 and a decreased Cdk2 kinase activity. In contrast to
      epithelial cells, however, TGF-beta1 had little or no effect on the Cdk4 and
      p21WAF1/Cip1 protein levels in these B cells. Finally, although several studies
      suggested a direct role of p53 in TGF-beta1-mediated cell cycle arrest in
      epithelial cells, TGF-beta1 inhibited cell cycle progression in CH31 even in the
      absence of wild-type p53. Taken together, these results suggest that TGF-beta1
      induces G1 arrest in B cells primarily through a p53-independent up-regulation of
      p27Kip1 protein.

PMID- 9551914
TI  - Role of proteasomes in T cell activation and proliferation.
AB  - The role of proteasomes in T cell activation, proliferation, and apoptosis was
      investigated using a proteasome-specific inhibitor lactacystin (LAC). Inhibition
      of the proteasome activity by LAC repressed the mitogen-induced T cell
      proliferation. The proteasome activity was definitively required for the T cells
      to progress from the G0 to S phase. It was necessary to optimize the progress
      from the G1/S boundary to the G2/M phase, but not for the progress from the G2/M
      phase to the next G1 phase. Probably as a result of a blockage of cell cycle
      progress, the cycling, but not the resting, T cells underwent apoptosis when
      treated with LAC. Mechanistically, we have found that cyclin-dependent kinase-2
      (CDK2) and the cyclin E-associated kinase (largely CDK2), but not CDK4, in the G1
      phase were strongly inhibited by LAC. This could be an important mechanism for
      the proteasome to regulate the cell cycle. The degradation of cyclin E in the
      late G1 and early S phases was dependent on the proteasome, although it was
      unlikely that this accounted for the observed inhibition of T cell proliferation.
      There was a reduced decay of p27Kip1 in the late G1 phase when the proteasome
      activity was suppressed, and this might be a contributing mechanism for the
      observed inhibition of CDK2 activity. Interestingly, p21Cip1 was up-regulated
      during the G1 phase, and the up-regulation was inhibited by LAC. Our study shows
      that the proteasome plays pivotal roles in regulating T cell activation and
      proliferation, and its effect is probably exerted through multiple mechanisms.

PMID- 9551915
TI  - Degenerate recognition of alloantigenic peptides on a positive-selecting class I
      molecule.
AB  - The well-defined 2C T cell was used to investigate alloreactive degeneracy. A
      panel of class I molecules that are known ligands for the 2C TCR were sensitized
      with three known peptide ligands, p2Ca (LSPFPFDL), dEV-8 (EQYKFYSV), and SIYR-8
      (SIYRYYGL). The peptide p2Ca was originally identified as the allopeptide seen in
      the Ld class I molecule by 2C T cells, 2C recognizes the dEV-8 peptide as the
      ligand in the Kbm3 class I molecule, and SIYR-8 was recently identified as a
      peptide ligand for 2C in the context of the Kb class I molecule. Strong
      recognition of all three Ag-presenting molecules occurred in the context of their
      respective allopeptides, but 2C recognized all three peptides to a measurable
      extent in the context of Kb. Molecular modeling of these Kb/peptide complexes
      revealed a high degree of similarity between dEV-8 and SIYR-8, but very little
      conformational similarity of either of these peptides with p2Ca. Furthermore, the
      structural changes in the mutant Kbm3 binding site resulted in generalized
      changes in the conformation of each of five bound peptides compared with those of
      the same peptides bound to Kb. The finding that degenerate recognition occurs on
      Kb, the restriction element responsible for selecting 2C T cells, suggests a
      unique relationship between a TCR and the Ag-presenting molecule that mediates
      its positive selection.

PMID- 9551916
TI  - Nuclear targeted suppression of NF-kappa B activity by the novel quinone
      derivative E3330.
AB  - The activation of NF-kappa B consists of at least three steps: degradation of I
      kappa B alpha, translocation of NF-kappa B into the nucleus, ai post
      translational modification of NF-kappa B (e.g., phosphorylation of p65). In the
      present study, we found that a novel quinone derivative E3330 selectively
      inhibited NF-kappa B-mediated gene expression without affecting any of these
      steps. E3330, when included in the culture medium, suppressed NF-kappa B DNA
      binding activity in PMA-induced Jurkat cell nuclear extracts, suggesting that the
      inhibition by E3330 of NF-kappa B-mediated gene expression was due to its ability
      to suppress NF-kappa B DNA-binding activity. Fractionation of the nuclear
      extracts by column chromatography revealed that a nuclear factor enhanced NF
      kappa B DNA-binding activity and that this enhancing activity was interrupted
      after treatment with E3330. Moreover, a major polypeptide with a molecular mass
      of 40 kDa was found to be in the highly purified fraction containing the NF-kappa
      B-enhancing activity and predominantly bind E3330. Taken together, these results
      suggest that the NF-kappa B activity, after dissociation from I kappa B, is
      enhanced by a nuclear factor that is active irrespective of PMA treatment, and
      the nuclear factor-mediated enhancement is selectively inhibited by E3330. Thus,
      we conclude that E3330 may belong to a novel class of anti-NF-kappa B drugs.

PMID- 9551918
TI  - Distinct patterns of folding and interactions with calnexin and calreticulin in
      human class I MHC proteins with altered N-glycosylation.
AB  - Calnexin is a lectin-like chaperone that binds to class I MHC molecules soon
      after their synthesis, retaining unassembled heavy chains and also assisting
      their folding. Following association with beta2-microglobulin (beta2m) in the
      endoplasmic reticulum, a large proportion of human class I molecules release from
      calnexin, whereas mouse class I molecules do not. We asked whether addition of a
      second N-glycan to the human class I molecule A*0201 at position 176, a site
      present in mouse, would affect its binding to calnexin. The 176dg mutant with N
      glycans at positions 86 and 176, when transfected into CIR cells, demonstrated
      increased binding to calnexin, detectable both before and after association with
      beta2m, and reduced interaction with calreticulin and TAP relative to wild-type
      protein bearing a single N-glycan at position 86. Cell surface levels of the
      mutant were decreased only slightly relative to the wild type, suggesting that
      the protein is not misfolded or grossly altered structurally. A subpopulation of
      mutant molecules was retained in the endoplasmic reticulum, and surprisingly,
      these molecules reacted with w6/32, which recognizes an epitope present on
      transport-competent class I HLA complexes. Transfection into Daudi cells
      demonstrated that 176dg reacts with w6/32 in the absence of beta2m, suggesting
      that the Ab epitope can be induced by binding of calnexin. These data may explain
      previously noted differences between mouse and human class I MHC proteins and
      demonstrate that the location of N-oligosaccharides within proteins can influence
      their folding and interactions with chaperones such as calnexin and calreticulin.

PMID- 9551917
TI  - Lack of intraclonal diversification in Ig heavy and light chain V region genes
      expressed by CD5+IgM+ chronic lymphocytic leukemia B cells: a multiple time point
      analysis.
AB  - To analyze the modalities of clonal expansion of chronic lymphocytic leukemia
      (CLL) cells, we sequenced at multiple time points the V(D)J genes expressed by
      CD5+IgM+CLL B cells in three patients. All three V(D)J gene sequences were found
      to be point mutated. The mutation frequency in the Ig VH (3.96 x 10(-2) and 2.41
      x 10(-2) change/bp) and Vkappa and Vlambda (6.67 x 10(-2) and 1.74 x 10(-2)
      change/bp) genes of two CLLs (1.19 and 1.32, respectively) was similar, and
      higher than that in the corresponding gene segments of the third CLL (1.69; 3.4 x
      10(-3) and 6.67 x 10(-3) change/bp). In all three CLLs, there was no preferential
      representation of nucleotide changes yielding amino acid replacement (R
      mutations), nor was there any preferential segregation of R mutations within the
      Ig V gene complementarity-determining regions. In all three CLLs, the somatic
      mutations were all identical in multiple Ig VHDJH transcripts at any given time
      point, and were all conserved at multiple time points throughout a 2-yr period.
      The lack of concentration of R mutations in the complementarity-determining
      regions and the lack of intraclonal heterogeneity suggest that Ag may no longer
      be able to play a significant role in the clonal expansion of these cells. This
      conclusion would be strengthened further by the germline configuration of the bcl
      1 and bcl-2 proto-oncogenes that are translocated in neoplastic B cells that
      display significant traces of intraclonal diversification and Ag-dependent
      selection, such as B-prolymphocytic leukemia and low grade follicular non-Hodgkin
      lymphoma.

PMID- 9551919
TI  - Activation of STAT5 by lipopolysaccharide through granulocyte-macrophage colony
      stimulating factor production in human monocytes.
AB  - LPS is a potent stimulator of monocytes, inducing many of their functions.
      Although the details of how LPS exerts such functions remain largely unknown,
      transcription factors such as nuclear factor-kappaB, nuclear factor-IL-6, and
      activator protein-1 have been shown to be involved in this process. However, to
      date it has been thought that no known STAT molecule plays a role in the
      activation of monocytes by LPS. In this study we examined whether some known STAT
      molecule is stimulated by LPS, based on the finding that a GAS motif sequence is
      conserved in the promoter regions of human, mouse, and rat cyclo-oxygenase-2 (COX
      2) genes. Consequently, LPS induced activation of STAT5 in human monocytes, and
      this STAT5 activation occurred in an indirect way via granulocyte-macrophage CSF
      (GM-CSF) secreted by LPS-stimulated monocytes. Expression of COX-2 protein was
      partially reduced by treatment of anti-human GM-CSF Ab. Activation of STAT5 was
      inhibited by either IL-10 or dexamethasone (Dex), but not by aspirin. IL-10
      blocked activation of STAT5 indirectly by suppressing GM-CSF production, while
      Dex inhibited this activation both directly and indirectly. Taken together, these
      results suggest that in addition to other transcription factors, STAT5 plays an
      important role in activation of monocytes by LPS, and that STAT5 is another
      target for IL-10 and Dex to inhibit COX-2 expression in activated monocytes.

PMID- 9551920
TI  - In vitro and in vivo mechanisms of action of the antiproliferative and
      immunosuppressive agent, brequinar sodium.
AB  - Intracellular pyrimidine nucleotides (PyN) can be synthesized de novo from
      glutamine, CO2, and ATP, or they can be salvaged from preformed pyrimidine
      nucleosides. The antiproliferative and immunosuppressive activities of brequinar
      sodium (BQR) are thought to be due to the inhibition of the activity of
      dihydroorotate dehydrogenase, which results in a suppression of de novo
      pyrimidine synthesis. Here we describe the effects of the pyrimidine nucleoSide,
      uridine, on the antiproliferative and immunosuppressive activities of BQR. In
      vitro reduction of PyN levels in Con A-stimulated T cells and inhibition of cell
      proliferation by low concentrations of BQR (< or =65 microM) are reversed by
      uridine. However, uridine is unable to reverse the effects of high concentrations
      of BQR (> or =65 microM). The ability of BQR to induce anemia in BALB/c mice is
      prevented by the coadministration of uridine. In contrast, the immunosuppressive
      activity of BQR is unaffected by similar doses of uridine. PyN levels in the bone
      marrow, but not in the spleen, are depressed in mice treated with BQR. These
      observations suggest that the induction of anemia by BQR is due to depletion of
      intracellular PyN in hemopoietic stem cells located in the bone marrow. They also
      suggest that the mechanism of immunosuppression by BQR may be only marginally
      dependent on depletion of intracellular PyN in lymphocytes located in the
      periphery. We report a novel activity of BQR: inhibition of tyrosine
      phosphorylation, and hypothesize that the immunosuppressive activity may be due,
      in part, to this unsuspected ability of BQR to inhibit tyrosine phosphorylation
      in lymphocytes.

PMID- 9551921
TI  - Separation of function between the domains of toxic shock syndrome toxin-1.
AB  - Toxic shock syndrome toxin-1 (TSST1) is a superantigenic exotoxin produced by
      certain strains of Staphylococcus aureus Structurally, TSST1 is composed of two
      domains: residues determined by crystallography to directly interact with MHC II
      molecules reside within the N-terminal domain, while TSST1 residues critical for
      superantigenicity are within the C-terminal domain. In this study, we expressed
      the individual N- and C-terminal domains of TSST1 in Escherichia coli and studied
      their biologic activities. The TSST1 N-terminal domain (TSST(1-87)) did not
      induce proliferation of human PBLs or release of TNF-beta, but did induce TNF
      alpha release. However, TSST1-elicited proliferation and release of both TNF
      isoforms were inhibited by a molar excess of TSST(1-87). The TSST1 C-terminal
      domain (TSST(88-194)) did not bind MHC II molecules, yet it elicited production
      of TNF-alpha and TNF-beta, and induced TCR Vbeta-specific proliferation similarly
      to intact TSST1. When covalently cross-linked to tumor cells, TSST(88-194)
      elicited a local in vivo antitumor response indistinguishable from TSST1.
      Although intact TSST1 causes lethal shock in vivo, the individual domains of this
      molecule may have therapeutic potential: the N-terminal domain to antagonize
      lymphocyte activation and TNF release during acute TSST1-precipitated toxic shock
      syndrome, and the C-terminal domain to stimulate antitumor responses without MHC
      II binding.

PMID- 9551922
TI  - Expression of two different antiphagocytic M proteins by Streptococcus pyogenes
      of the OF+ lineage.
AB  - All clinical isolates of Streptococcus pyogenes (group A streptococcus) share the
      ability to resist phagocytosis and grow in human blood. In many strains, this
      property is due to the expression of a single antiphagocytic M protein, while
      other strains express more than one M-like molecule, of which the role in
      phagocytosis resistance is unclear. In particular, all S. pyogenes strains of the
      OF+ lineage, representing approximately half of all isolates, express two M-like
      proteins, Mrp and Emm, which are immunologically unrelated. These two proteins
      bind different ligands that have been implicated in phagocytosis resistance: Mrp
      binds fibrinogen and Emm binds the complement inhibitor C4BP. Using a clinical
      isolate of the common serotype 22, we created mutants affected in the mrp and emm
      genes and characterized them in phagocytosis experiments and by electron
      microscopy. A double mutant mrp-emm- showed strongly decreased resistance to
      phagocytosis, while mrp- and emm- single mutants grew well in blood. However,
      optimal growth required the expression of both Mrp and Emm. Experiments in which
      coagulation was inhibited using the specific thrombin inhibitor, hirudin, rather
      than heparin, indicated that Emm is more important than Mrp for resistance to
      phagocytosis. Tuftlike surface structures typical for S. pyogenes were still
      present in the mrp-emm- double mutant, but not in a mutant affected in the
      regulatory gene mga, indicating that the presence of these surface structures is
      not directly correlated to phagocytosis resistance. Our data imply that OF+
      strains of S. pyogenes express two antiphagocytic M proteins with different
      ligand-binding properties.

PMID- 9551923
TI  - CpG DNA is a potent enhancer of specific immunity in mice immunized with
      recombinant hepatitis B surface antigen.
AB  - Unmethylated CpG dinucleotides in bacterial DNA or synthetic
      oligodeoxynucleotides (ODN) cause B cell proliferation and Ig secretion, monocyte
      cytokine secretion, and activation of NK cell lytic activity and IFN-gamma
      secretion in vivo and in vitro. The potent immune activation by CpG ODN suggests
      possible utility for enhancing immune responses to vaccines. Mice immunized with
      recombinant hepatitis B virus surface Ag and a CpG ODN as an immune enhancer have
      titers of Abs against HBsAg (anti-HBs) that are five times higher than those of
      mice immunized with HBsAg and the standard adjuvant, aluminum hydroxide (alum).
      Ab titers in mice immunized with HBsAg and both CpG ODN plus alum were 35 times
      higher than the titers in mice immunized with alum alone, indicating a strong
      synergistic interaction between the CpG ODN and alum. ODN without CpG motifs had
      little or no immune-enhancing activity at the doses used herein. Alum induces a
      Th2 humoral response (mostly IgG1) and no CTL. In contrast, CpG ODN gives a
      strong Thl response with predominantly IgG2a Abs and CTL, even when mixed with
      alum. In vitro studies to determine possible mechanisms of CpG immune-enhancing
      effects show that CpG ODN induce expression of costimulatory molecules on Ag
      presenting cells and drive B cell isotype switching in the appropriate cytokine
      milieu. These studies demonstrate that CpG ODN are promising new immune enhancers
      for vaccination applications.

PMID- 9551924
TI  - Identification and characterization of the CXCR4 chemokine receptor in human T
      cell lines: ligand binding, biological activity, and HIV-1 infectivity.
AB  - The CXCR4 chemokine receptor has been shown to respond to the C-X-C chemokine
      stromal-derived factor (SDF-1) and has recently been shown to be an important
      coreceptor for HIV-1 infection. In the present paper we have tested a number of
      human lymphocyte cell lines, including Jurkat, HUT78, CEM, and Sup-T1 for the
      presence of CXCR4 receptors. We found that these T cell lines bind SDF-1alpha and
      SDF-1beta with high affinity. The CXCR4 Ab 12G5 inhibited both SDF-1 binding and
      HIV-1LAI-mediated fusion of CEM. Scatchard analysis revealed the presence of
      approximately 150,000 SDF-1alpha-binding sites per cell with a Kd between 5 and
      10 nM. Cross-competition experiments using unlabeled SDF-1alpha and SDF-1beta
      revealed that both chemokines are equally capable of displacing their
      radiolabeled counterparts. Internalization studies with [125]I-SDF-1alpha
      revealed that Jurkat cells internalized greater than 90% of the ligand by 2 h at
      37 degrees C. SDF-1alpha was also chemotactic for Jurkat cells and caused an
      increase in the rate of extracellular acidification that was half-maximal at 18
      nM SDF-1alpha and could be inhibited by pretreatment with the SDF-1 proteins,
      pertussis toxin, or the Ab 12G5. Finally, SDF-1alpha also caused an increase in
      the cytosolic Ca2+ concentration in Sup-T1 cells that was abolished by
      preincubating the cells with pertussis toxin or PMA and inhibited by the Ab 12G5.
      This molecular characterization of CXCR4 receptors should prove useful in
      clarifying receptor interaction with SDF-1 proteins and with HIV-1 glycoprotein,
      with the ultimate aim of targeting the viral interaction for therapeutic
      intervention.

PMID- 9551925
TI  - Control of Leishmania major by a monoclonal alpha beta T cell repertoire.
AB  - Little is known regarding the diversity of the host T cell response that is
      required to maintain immunologic control of microbial pathogens. Leishmania major
      persist as obligate intracellular parasites within macrophages of the mammalian
      host. Immunity is dependent upon activation of MHC class II-restricted T cells to
      an effector state capable of restricting growth and dissemination of the
      organisms. We generated alpha-beta Leishmania-specific (ABLE) TCR transgenic mice
      with MHC class II-restricted T cells that recognized an immunodominant Leishmania
      Ag designated LACK. Naive T cells from ABLE mice proliferated in vitro after
      incubation with recombinant LACK or with Leishmania-parasitized macrophages and
      in vivo after injection into infected mice. Infected ABLE mice controlled
      Leishmania infection almost as well as wild-type mice despite a drastic reduction
      in the T cell repertoire. ABLE mice were crossed to mice with disruption of the
      TCR constant region alpha gene to create animals with a single alpha beta T cell
      repertoire. Although mice deficient in all alpha beta T cells (TCR-C alpha 0
      mice) failed to control L. major, mice with a monoclonal alpha beta T cell
      repertoire (ABLE TCR-C alpha 0 mice) displayed substantial control. The immune
      system is capable of remarkable efficiency even when constrained to recognition
      of a single epitope from a complex organism.

PMID- 9551926
TI  - Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by
      CTL in the context of HLA-A31 and -A33.
AB  - Tumor-infiltrating lymphocytes (TILs) derived from tumor-bearing patients
      recognize tumor-associated Ags presented by MHC class I molecules. The infusion
      of TIL586 along with IL-2 into the autologous patient with metastatic melanoma
      resulted in the objective regression of tumor. Two T cell epitopes derived from
      tumor Ags, tyrosinase-related protein (TRP)-1 and TRP-2, were shown to be
      recognized by HLA-A31 restricted TIL586 and its T cell clones. In this study we
      tested the hypothesis that these two peptides can be recognized by CTL from non
      HLA-A31 patients with melanoma. It was found that both peptides were capable of
      binding to HLA-A3, -A11, -A31, -A33, and -A68 of the HLA-A3 supertype.
      Importantly, we found that HLA-A33-positive TIL1244 and its T cell clones can
      recognize TRP197-205 presented by both HLA-A31 and -A33 molecules, suggesting
      that a single TCR can recognize peptide/A31 and peptide/A33 complexes. However,
      peptide titration experiments showed that the affinity of TCR receptor to
      peptide/A33 could be higher than that to the peptide/A31. These studies have
      important implications for the development of peptide-based cancer vaccines.

PMID- 9551927
TI  - Perforin-deficient CD8+ T cells provide immunity to Listeria monocytogenes by a
      mechanism that is independent of CD95 and IFN-gamma but requires TNF-alpha.
AB  - CD8+ T cells are effective mediators of immunity against Listeria monocytogenes,
      but the mechanisms by which they provide antilisterial immunity are poorly
      understood. CD8+ T cells efficiently lyse target cells in vitro by at least two
      independent pathways. To test the hypothesis that CD8+ T cell-mediated immunity
      to L. monocytogenes is dependent on perforin or CD95 (Fas, Apo-1), we used
      C57BI/6 (B6) and perforin-deficient (PO) mice to generate CD8+ T cell lines
      specific for the L. mono cytogenes-encoded Ag listeriolysin O (LLO). Both lines
      specifically produce IFN-gamma and TNF-alpha, and mediate target cell lysis in
      vitro. Cytolysis mediated by the PO-derived CD8+ T cell line is delayed relative
      to the B6-derived line and is completely inhibited by anti-CD95 Abs. In vivo, PO
      derived CD8+ T cells provide specific antilisterial immunity in B6 hosts, CD95
      deficient hosts, and IFN-gamma-depleted hosts. However, PO-derived CD8+ T cells
      fail to provide antilisterial immunity in hosts depleted of TNF-alpha. These
      results indicate that single Ag-specific CD8+ T cells derived from PO mice can
      mediate antilisterial immunity by a mechanism that is independent of CD95 or IFN
      gamma, but requires TNF-alpha.

PMID- 9551928
TI  - CXC chemokines suppress proliferation of myeloid progenitor cells by activation
      of the CXC chemokine receptor 2.
AB  - IL-8 is one of the major mediators of the transendothelial migration of
      neutrophils from the circulation to the site of injury and infection. In this
      work we demonstrate that the CXC or alpha-chemokines, IL-8 and melanoma growth
      stimulatory activity (MGSA) induce myeloid suppression via direct action on
      progenitor cells, mediated by activation of the murine homologue of the CXC
      chemokine receptor-2 (CXCR2) or IL-8R B. We first show that proliferation of the
      IL-3-dependent murine myeloid progenitor cell line 32D is suppressed by human IL
      8 and the functionally and structurally related peptide, MGSA. Second, we show
      for the first time the high endogenous expression of the murine CXCR2 in 32D
      cells, as demonstrated by Northern blot analysis, binding to [125I]macrophage
      inflammatory protein-2, and macrophage inflammatory protein-2-induced calcium
      responses in 32D cells. Third, we demonstrate that IL-8 and MGSA induce a rise in
      intracellular calcium in 32D cells. The IL-8-induced Ca2+ response is
      desensitizing, since a second dose of IL-8 did not trigger a second calcium
      response. Other chemokines, including neutrophil-activating protein-2, platelet
      factor-4, RANTES, and macrophage chemotactic protein-1, neither suppressed the
      proliferation of 32D cells nor induced a rise in intracellular calcium. Finally,
      the IC50 of IL-8- and MGSA-dependent suppression of proliferation of 32D cells is
      in good agreement with the EC50 of IL-8- and MGSA-dependent activation of
      neutrophil Mac-1 up-regulation and chemotaxis. Our studies are consistent with
      the idea that IL-8 and MGSA suppress the proliferation of 32D cells by activation
      of murine CXCR2.

PMID- 9551929
TI  - High affinity receptor for IgG (Fc gamma RI/CD64) gene and STAT protein binding
      to the IFN-gamma response region (GRR) are regulated differentially in human
      neutrophils and monocytes by IL-10.
AB  - Since IL-10 has been shown to up-regulate the expression of the high affinity
      receptor for IgG (FcgammaRI/CD64) in human monocytes, we examined whether the
      cytokine exerts a similar action toward polymorphonuclear neutrophils (PMN).
      Unexpectedly, we found that in neutrophils, IL-10 failed to induce either the
      mRNA accumulation or the surface expression of FcgammaRI. Consistent with these
      findings, stimulation of PMN with IFN-gamma, but not with IL-10, resulted in the
      induction of specific DNA-binding activities to the IFN-gamma response region
      (GRR), a regulatory element located in the FcgammaRI gene promoter, required for
      transcriptional activation. In electrophoretic mobility shift assays (EMSAs), we
      confirmed that in PBMC, IL-10 induces the binding to the GRR of both STAT1 and
      STAT3, two members of the STAT family. In neutrophils, however, these activators
      did not bind to the GRR in response to IL-10, despite the fact that both STAT1
      and STAT3 are expressed in these cells. On the other hand, IFN-gamma was an
      efficient inducer of STAT1 binding to the GRR in both PMN and PBMC. The lack of
      inducible GRR-binding activity in IL-10-treated PMN could not be ascribed to a
      lack of IL-10R, and did not appear to reflect an inhibitory effect of the
      cytokine. Taken together, our data suggest that IL-10 is unable to induce
      FcgammaRI gene expression in neutrophils because the intracellular signaling
      pathway triggered by the cytokine is impaired at the level of, or upstream of,
      STAT1 and/or STAT3 activation.

PMID- 9551930
TI  - Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: role of
      the p38 and p42/44 mitogen-activated protein kinases.
AB  - IL-10 is an anti-inflammatory cytokine with potent immunomodulatory effects,
      including inhibition of cytokine production. However, regulation of monocyte IL
      10 production is poorly understood. In this report we have investigated the
      mechanisms of LPS-induced IL-10 production by human peripheral blood monocytes
      and demonstrate that IL-10 synthesis is uniquely dependent on the endogenous
      proinflammatory cytokines IL-1 and/or TNF-alpha. LPS signal transduction in
      monocytes has been shown to involve activation of the p38 and p42 mitogen
      activated protein kinase (MAPK) cascades. The results in this paper indicate that
      inhibition of p38 MAPK potently inhibited the production of IL-10, IL-1beta, and
      TNF-alpha, whereas blockade of the p42/44 MAPK pathway, while partially
      inhibiting TNF-alpha and IL-1beta production, had no effect on monocyte secretion
      of IL-10. Furthermore, neither the inhibition of monocyte TNF-alpha induced by IL
      10 nor the stimulation of soluble TNF receptor production was affected by
      inhibition of the p42/44 MAPK pathway, suggesting that this signaling event is
      not involved in either monocyte production of or anti-inflammatory responses to
      IL-10. These data raise the interesting possibility that proinflammatory TNF
      alpha-mediated effects may be selectively blocked without modulating the
      induction or the response to IL-10, whereas the signaling events associated with
      the anti-inflammatory events induced by IL-10 remain to be elucidated.

PMID- 9551931
TI  - Prostaglandin E2 modulation of p59fyn tyrosine kinase in T lymphocytes during
      sepsis.
AB  - Prostaglandin E2 (PGE2) has been implicated in the suppression of T cell IL-2
      production and proliferation during burn and sepsis. The present study evaluated
      the potential intracellular mechanism of suppressed T cell responses by assessing
      the activation of p59fyn kinase in T cells from septic rats as well as the T
      cells incubated with PGE2. p59fyn is known to regulate T cell functions. Sepsis
      was induced in rats by implanting fecal pellets containing Escherichia coli (150
      CFU) and Bacteroides fragilis (10(4) CFU) into the abdominal cavity. For the
      assessment of PGE2 role in sepsis, a group of septic rats were treated with
      indomethacin, which inhibits endogenous PGE2 synthesis. As assessed by
      immunoblotting or in vitro kinase assay, a more than 40% inhibition of p59fyn
      phosphorylation and kinase activity was observed in septic rat T cells compared
      with the T cells from sterile or control rats. A similar inhibition in p59fyn
      phosphorylation and kinase activity was observed in PGE2-treated T cells compared
      with the T cells incubated in the absence of PGE2. The septic-related suppression
      in p59fyn phosphorylation and kinase activity in T cells was prevented in rats
      treated with indomethacin. We observed that the inhibition in p59fyn activation
      in septic or PGE2-treated T cells was due primarily to a suppression in p59fyn
      phosphorylation and not due to alterations in p59fyn protein expression. These
      findings suggest that PGE2 released during sepsis could contribute to the sepsis
      related suppression in T cell proliferation by attenuating p59fyn phosphorylation
      and its kinase activity.

PMID- 9551932
TI  - Translational efficiency is up-regulated by alternative exon in murine IL-15
      mRNA.
AB  - IL-15 promotes the growth of T cells and shares properties of IL-2. IL-2 is
      produced exclusively by T cells, while IL-15 message is expressed by a variety of
      tissues. However, it has been difficult to demonstrate IL-15 in the supernatants
      of many cells that express message for this cytokine. This suggests that IL-15
      production is regulated by post-transcriptional controls. In this study, we
      cloned three types of murine IL-15 cDNA isoforms generated by alternative
      splicing and compared the translational efficiency among these isoforms. The
      translational efficiency of isoforms with alternative exon 5 containing another
      3' splice site was significantly higher than that of IL-15 cDNA with originally
      described exon 5, which is generated by internal splicing of alternative exon 5.
      The translation product of the isoform containing alternative exon 5 has a
      shorter open reading frame due to stop codons in additional sequence, followed by
      a new AUG codon, and displays a shorter leader sequence. The shorter isoform of
      the IL-15 was detected in peritoneal macrophages stimulated with IFN-gamma and
      LPS, which expressed an abundant level of alternative exon 5. These results
      suggest that normal IL-15 production in stimulated macrophages is regulated by
      splicing of alternative exon 5.

PMID- 9551933
TI  - TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several
      models of inflammation.
AB  - The pleiotropic activities of the potent proinflammatory cytokine TNF are
      mediated by two structurally related, but functionally distinct, receptors, p55
      and p75, that are coexpressed on most cell types. The majority of biologic
      responses classically attributed to TNF are mediated by p55. In contrast, p75 has
      been proposed to function as both a TNF antagonist by neutralizing TNF and as a
      TNF agonist by facilitating the interaction between TNF and p55 at the cell
      surface. We have examined the roles of p55 and p75 in mediating and modulating
      the activity of TNF in vivo by generating and examining mice genetically
      deficient in these receptors. Selective deficits in several host defense and
      inflammatory responses are observed in mice lacking p55 or both p55 and p75, but
      not in mice lacking p75. In these models, the activity of p55 is not impaired by
      the absence of p75, arguing against a physiologic role for p75 as an essential
      element of p55-mediated signaling. In contrast, exacerbated pulmonary
      inflammation and dramatically increased endotoxin induced serum TNF levels in
      mice lacking p75 suggest a dominant role for p75 in suppressing TNF-mediated
      inflammatory responses. In summary, these data help clarify the biologic roles of
      p55 and p75 in mediating and modulating the biologic activity of TNF and provide
      genetic evidence for an antagonistic role of p75 in vivo.

PMID- 9551934
TI  - Distinct phospholipases A2 regulate the release of arachidonic acid for
      eicosanoid production and superoxide anion generation in neutrophils.
AB  - Arachidonic acid (AA) released from membrane phospholipids by phospholipase A2
      (PLA2) is important as a substrate for eicosanoid formation and as a second
      messenger for superoxide anion (O2-) generation in neutrophils. Different
      isoforms of PLA2 in neutrophils might mobilize AA for different functions. To
      test this possibility, we sought to characterize the PLA2s that are activated by
      the neutrophil stimuli, Aroclor 1242, a mixture of polychlorinated biphenyls, and
      A23187, a calcium ionophore. Both Aroclor 1242 and A23187 caused release of
      [3H]AA; however, O2- production was seen only in response to Aroclor 1242.
      Eicosanoids accounted for >85% of the radioactivity recovered in the supernatant
      of A23187-stimulated cells but <20% of the radioactivity recovered from cells
      exposed to Aroclor 1242. Omission or chelation of calcium abolished A23187
      induced AA release, but did not alter AA release in Aroclor 1242-stimulated
      neutrophils. AA release and O2- production in response to Aroclor 1242 were
      inhibited by bromoenol lactone (BEL), an inhibitor of calcium-independent PLA2.
      BEL, however, did not alter Calcium-independent activity was inhibited >80% by
      BEL, whereas calcium-dependent activity was inhibited <5%. Furthermore, calcium
      independent, but not calcium-dependent, PLA2 activity was significantly enhanced
      by Aroclor 1242. These data suggest that Aroclor 1242 and A23187 activate
      distinct isoforms of PLA2 that are linked to different functions: Aroclor 1242
      activates a calcium-independent PLA2 that releases AA for the generation of O2-,
      and A23187 activates a calcium-dependent PLA2 that mobilizes AA for eicosanoid
      production.

PMID- 9551935
TI  - Fever-range hyperthermia enhances L-selectin-dependent adhesion of lymphocytes to
      vascular endothelium.
AB  - The L-selectin leukocyte adhesion molecule plays an important role in controlling
      leukocyte extravasation in peripheral lymph nodes and at sites of tissue injury
      or infection. Although febrile responses during infection and inflammation are
      associated with enhanced immune activity, the contribution of fever-range
      temperatures to controlling lymphocyte recruitment to tissues has not been
      previously examined. In this report we provide evidence that direct exposure of
      lymphocytes to fever-range temperatures (38-41 degrees C) in vitro for 9 to 24 h
      resulted in a >100% increase in L-selectin-dependent adhesion of these cells to
      lymph node high endothelial venules (HEV). Moreover, culture of lymphocytes under
      hyperthermia conditions markedly enhanced the ability of these cells to traffic
      in an L-selectin-dependent manner to peripheral lymph nodes, mesenteric lymph
      nodes, and Peyer's patches. In contrast, febrile temperatures did not increase
      LFA-1 function as assessed by measuring lymphocyte adhesion to ICAM-1-3T3
      transfectants. Fever-range hyperthermia further did not increase L-selectin
      surface density on lymphocytes or L-selectin-dependent recognition of soluble
      carbohydrate substrates; however, a marked increase in ultrastructural immunogold
      labeling of L-selectin was observed in response to thermal stimuli. These results
      suggest that elevated temperatures enhance L-selectin adhesion and/or avidity
      through the regulation of L-selectin conformation or organization in the plasma
      membrane. Finally, the observed thermal effects on L-selectin adhesion were
      attributed to soluble factors in the conditioned medium of heat-treated cells.
      Taken together, these data provide new insight into the potential physiologic
      role of the febrile response in enhancing lymphocyte recruitment to tissues
      through the regulation of L-selectin adhesion.

PMID- 9551936
TI  - Dynamic regulation of alpha- and beta-chemokine expression in the central nervous
      system during mouse hepatitis virus-induced demyelinating disease.
AB  - Infection of C57BL/6 mice with the V5A13.1 strain of mouse hepatitis virus (MHV
      V5A13.1) results in an acute encephalomyelitis and chronic demyelinating disease
      with features similar to the human demyelinating disease multiple sclerosis.
      Chemokines are a family of proinflammatory cytokines associated with inflammatory
      pathology in various diseases. The kinetics and histologic localization of
      chemokine production in the central nervous system of MHV-infected mice were
      examined to identify chemokines that contribute to inflammation and
      demyelination. Transcripts for the chemokines cytokine-response gene-2 (CRG-2),
      regulated on activation, normal T cell expressed and secreted (RANTES),
      macrophage-chemoattractant protein-1 and protein-3 (MCP-1, MCP-3), macrophage
      inflammatory protein-1beta (MIP-1beta), and MIP-2 were detected in the brains of
      MHV-infected mice at 3 days postinfection (p.i.), and these transcripts were
      increased markedly in brains and spinal cords at day 7 p.i., which coincides with
      the occurrence of acute viral encephalomyelitis. By day 35 p.i., RANTES, CRG-2,
      and MIP-1beta were detected in brains and spinal cords of mice with chronic
      demyelination. CRG-2 mRNA expression colocalized with viral RNA and was
      associated with demyelinating lesions. Astrocytes were the predominant cell type
      expressing CRG-2 mRNA. These observations suggest a role for chemokines, notably
      CRG-2, in the initiation and maintenance of an inflammatory response following
      infection with MHV, which is important in contributing to demyelination.

PMID- 9551938
TI  - Gene organization and promoter function for CC chemokine receptor 5 (CCR5).
AB  - CC chemokine receptor 5 (CCR5) functions physiologically as a receptor for the
      leukocyte chemoattractants macrophage inflammatory protein-1alpha, macrophage
      inflammatory protein-1beta, and RANTES, and functions pathologically as a key
      cell entry coreceptor for HIV-1. The factors that regulate CCR5 expression may be
      useful therapeutic targets for HIV-1 infection. To identify nuclear regulatory
      factors, we have located and functionally characterized the CCR5 gene promoter.
      The gene consists of two exons separated by a 1.9-kb intron. Exon 1 contains 43
      bp of the 5'-untranslated region; exon 2 contains 11 bp of the 5'-untranslated
      region and the complete open reading frame. Primer extension analysis identified
      two adjacent transcriptional start points (tsp) that map to the first 2 bp found
      in the longest known CCR5 cDNA sequence. A TATA box is present 31 bp upstream
      from the first tsp. CCR5 mRNA was detected constitutively in both primary human
      myeloid and lymphoid cells by Northern blot hybridization. Consistent with this,
      transcription of a chloramphenicol acetyltransferase reporter gene was
      constitutively activated in both transiently transfected myeloid and lymphoid
      cell lines by the 80-bp gene fragment located immediately upstream of the tsp.
      Deletion analysis located a strong silencer element between nucleotides -244 and 
      80, and a strong enhancer element between -486 and -244. These results suggest
      that the gene region between -486 and -1 may regulate the expression of CCR5 in
      monocyte/macrophages and T lymphocytes.

PMID- 9551937
TI  - IL-4 is an endogenous inhibitor of neutrophil influx and subsequent pathology in
      acute antibody-mediated inflammation.
AB  - IL-4 is an immunoregulatory cytokine that has in vitro and in vivo anti
      inflammatory actions. In this study we investigated whether endogenously produced
      IL-4 modulates inflammatory processes that occur after Abs bind to target tissue
      by comparing the severity of glomerulonephritis induced by heterologous anti
      glomerular basement membrane Abs in wild-type (IL-4+/+) mice to that of
      glomerulonephritis induced in homozygous IL-4 gene knockout (IL-4-/-) mice. Two
      hours after Ab injection, IL-4-/- mice had significantly higher intrarenal
      intercellular adhesion molecule-1 mRNA expression and intraglomerular neutrophil
      accumulation than the IL-4+/+ group. Treatment of IL-4-/- mice with recombinant
      murine IL-4 at the time of disease induction reduced intercellular adhesion
      molecule-1 expression and neutrophil influx to levels observed in IL-4+/+
      kidneys. Four days after Ab administration, untreated IL-4-/- mice developed
      significantly greater urinary protein excretion, intracapillary fibrinogen
      deposits, and glomerular hypercellularity than IL-4+/+ mice. These results
      demonstrate that endogenous IL-4 suppresses neutrophil influx and limits tissue
      damage in Ab-induced glomerulonephritis, suggesting that IL-4 is an important
      regulator of acute inflammatory processes.

PMID- 9551940
TI  - Thymosin alpha 1 stimulates endothelial cell migration, angiogenesis, and wound
      healing.
AB  - In wound healing, lymphoid cells release soluble factors that attract fibroblasts
      and macrophages, initiating repair, endothelial cell migration, angiogenesis, and
      matrix production. We analyzed the effect of thymosin alpha1 (Talpha1) on
      endothelial cell migration, angiogenesis, and wound healing. Talpha1, a 28 amino
      acid peptide initially isolated from the thymus, enhanced the morphologic
      differentiation of endothelial cells and was a potent chemoattractant for
      endothelial cells and monocytes in vitro. In vivo, Talpha1 stimulated
      angiogenesis in a subcutaneous model. When given either topically or i.p., it
      accelerated wound healing in a punch model, demonstrating that Talpha1 promotes
      angiogenesis and wound healing.

PMID- 9551939
TI  - Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin.
AB  - The ability of T cells to adhere to and interact with components of the blood
      vessel walls and the extracellular matrix is essential for their extravasation
      and migration into inflamed sites. We have found that the beta1 integrin-mediated
      adhesion of resting human T cells to fibronectin, a major glycoprotein component
      of the extracellular matrix, is induced by physiologic concentrations of three
      neuropeptides: calcitonin gene-related protein (CGRP), neuropeptide Y, and
      somatostatin; each acts via its own specific receptor on the T cell membrane. In
      contrast, substance P (SP), which coexists with CGRP in the majority of
      peripheral endings of sensory nerves, including those innervating the lymphoid
      organs, blocks T cell adhesion to fibronectin when induced by CGRP, neuropeptide
      Y, somatostatin, macrophage inflammatory protein-1beta, and PMA. Inhibition of T
      cell adhesion was obtained both by the intact SP peptide and by its 1-4 N
      terminal and its 4-11, 5-11, and 6-11 C-terminal fragments, used at similar
      nanomolar concentrations. The inhibitory effects of the parent SP peptide and its
      fragments were abrogated by an SP NK-1 receptor antagonist, suggesting they all
      act through the same SP NK-1 receptor. These findings suggest that neuropeptides,
      by activating their specific T cell-expressed receptors, can provide the T cells
      with both positive (proadhesive) and negative (antiadhesive) signals and thereby
      regulate their function. Thus, neuropeptides may influence diverse physiologic
      processes involving integrins, including leukocyte-mediated migration and
      inflammation.

PMID- 9551941
TI  - Neutrophils are major contributors to intraparenchymal lung IL-1 beta expression
      after hemorrhage and endotoxemia.
AB  - Acute lung injury and the acute respiratory distress syndrome (ARDS) are
      significant causes of morbidity and mortality following sepsis and hemorrhage.
      Increased IL-1beta production in the lung is important in the development of
      acute inflammatory lung injury. Although neutrophils are an important component
      of the inflammatory response that characterizes acute lung injury, there is
      little information to suggest that they are capable of initiating cytokine
      mediated immune responses in the lung. To explore the role of neutrophils in the
      early stages of acute lung injury, we examined IL-1beta production by mouse lung
      neutrophils after hemorrhage and endotoxemia. There was a significant increase in
      IL-1beta expression among intraparenchymal pulmonary neutrophil/mononuclear cells
      (IPNMC) 1 h after hemorrhage or endotoxemia. IL-1beta was detected only in a
      neutrophil-rich fraction of the IPNMC, but not in T and B lymphocytes positively
      selected from the IPNMC. Cyclophosphamide (CTX)-treated neutropenic mice
      expressed significantly less IL-1beta in IPNMC after hemorrhage or endotoxemia
      compared with CTX-untreated controls. Immunohistochemical analysis of lung
      sections from mice after hemorrhage or endotoxemia revealed IL-1beta expression
      in infiltrating neutrophils. These data indicate that IL-1beta-producing
      neutrophils traffic to the lungs rapidly in response to hemorrhage or endotoxemia
      and support the concept that proinflammatory cytokine production by lung
      neutrophils may contribute to the development of lung injury after blood loss and
      sepsis.

PMID- 9551942
TI  - Requirements for alpha d in IgG immune complex-induced rat lung injury.
AB  - Alpha d is a newly cloned adhesion molecule that forms a heterodimer with CD18.
      The requirement for alpha d in IgG immune complex-induced lung injury in rats has
      been evaluated by the use of blocking polyclonal and monoclonal antibodies to rat
      alpha d. Using whole lung extracts, Northern and Western blot analyses have
      revealed up-regulation of mRNA and alpha d protein in inflamed lungs.
      Immunostaining has revealed the presence of alpha d in lung tissue and in
      alveolar macrophages as early as 1 h after initiation of the inflammatory
      reaction. When polyclonal rabbit Ab to rat alpha d was coinstilled into lung
      together with Ab to BSA, lung injury (as determined by leakage of [125I]albumin
      into lung parenchyma) was significantly diminished. In parallel, there was
      reduced accumulation of neutrophils recoverable in bronchoalveolar lavage (BAL)
      fluids. These findings were associated with reduced levels of TNF-alpha as well
      as NO2-/NO3- in BAL fluids. A hamster mAb to rat alpha d was also protective in
      this lung injury model. Anti-alpha d inhibited in vitro production of NO2-/NO3-
      by rat alveolar macrophages (stimulated with LPS and IFN-gamma) by approximately
      60%. These data suggest that, in the lung inflammatory model employed, alpha d up
      regulation occurs in lung macrophages and is necessary for expression of TNF
      alpha, recruitment of neutrophils, and full development of lung injury.

PMID- 9551943
TI  - T helper 1 response is dominant and localized to the synovial fluid in patients
      with Lyme arthritis.
AB  - Cytokines produced by subsets of CD4+ T helper cells responding to an infection
      influences the efficiency with which the host is able to mount a protective
      immune response. In an attempt to elucidate the population of active cells
      involved in the propagation of Lyme arthritis we have utilized intracellular
      cytokine staining to analyze the polyclonal immune response at the single cell
      level. We have determined the Th phenotype in the synovial fluid of patients with
      a variety of chronic inflammatory arthritides, including patients representative
      of the spectrum of Lyme arthritis. Th1 cells dominate the immune response in the
      synovial fluid of patients with Lyme as well as those with rheumatoid or other
      types of chronic inflammatory arthritis. In addition, the severity of Lyme
      arthritis directly correlates with the ratio of Th1 to Th2 cells in the synovial
      fluid, such that the larger the effusion, the higher the ratio (r = 0.67, p <
      0.05). These results suggest that Th1 cells play a direct role in the
      pathogenesis of the inflammatory process seen in Lyme arthritis, and that Th2
      cells modulate the pro-inflammatory response generated by Th1 cells in the joint.
      Finally, we identify Th1 cells specific for outer surface protein A of Borrelia
      burgdorferi, the agent of Lyme disease. These cells are restricted to patients
      with Lyme arthritis and are localized to the joint. Furthermore, they persist in
      patients with prolonged antibiotic treatment-resistant Lyme arthritis, suggesting
      the possibility of an autoimmune process.

PMID- 9551944
TI  - Humanization and pharmacokinetics of a monoclonal antibody with specificity for
      both E- and P-selectin.
AB  - E- and P-selectin (CD62E and CD62P) are cell adhesion molecules that mediate
      leukocyte-endothelial cell and leukocyte-platelet interactions and are involved
      in leukocyte recruitment during inflammation. We previously developed a murine
      mAb, EP-5C7 (or mEP-5C7), that binds and blocks both E- and P-selectin. When used
      in humans, murine mAbs have short circulating half-lives and generally induce
      potent human anti-mouse Ab responses. We therefore engineered a humanized,
      complementarity determining region-grafted version of mEP-5C7 incorporating human
      gamma4 heavy and kappa light chain constant regions (HuEP5C7.g4). HuEP5C7.g4
      retains the specificity and avidity of mEP-5C7, binding to human E- and P
      selectin but not to human L-selectin, and blocking E- and P-selectin-mediated
      adhesion. Surprisingly, when administered to rhesus monkeys, HuEP5C7.g4 was
      eliminated from the circulation very rapidly, even faster than the original
      murine Ab. To isolate the cause of the short serum half-life of HuEP5C7.g4,
      several Ab variants were constructed. A chimeric IgG4 Ab was made by replacing
      the humanized V regions with murine V regions. A humanized IgG2 Ab, HuEP5C7.g2,
      was also made by replacing the human gamma4 with a gamma2 constant region.
      Results from pharmacokinetic studies in rhesus monkeys demonstrated that the
      chimeric IgG4 is also rapidly eliminated rapidly from serum, similar to the
      humanized IgG4 Ab, while the humanized IgG2 Ab displays a long circulation half
      life, typical of human Abs.

PMID- 9551945
TI  - Development of murine allergic asthma is dependent upon B7-2 costimulation.
AB  - Allergic asthma is thought to be mediated by CD4+ T lymphocytes producing the Th2
      associated cytokines, IL-4, and IL-5. Recently, the costimulatory molecules B7-1
      and B7-2, which are expressed on the surface of APC, have been suggested to
      influence the development of Th1 vs Th2 immune responses. We examined the in vivo
      role of these costimulatory molecules in the pathogenesis of Th2-mediated
      allergen-induced airway hyperresponsiveness in a murine model of asthma. In this
      model, OVA-sensitized A/J mice develop significant increases in airway
      responsiveness, pulmonary eosinophilia, and pulmonary Th2 cytokine expression
      following aspiration challenge with OVA as compared with PBS-control animals.
      Strikingly, administration of anti-B7-2 mAb to OVA-treated mice abolished
      allergen-induced airway hyperresponsiveness, pulmonary eosinophilia, and
      elevations in serum IgG1 and IgE levels. Anti-B7-2 treatment of OVA-treated mice
      reduced both total lung IL-4 and IL-5 mRNA and bronchoalveolar lavage fluid IL-4
      and IL-5 protein levels, with no significant changes in IFN-gamma message or
      protein levels. In contrast, treatment with anti-B7-1 mAbs had no effect on
      allergen-induced airway hyperresponsiveness, IgE production, or cytokine
      production, however, it significantly suppressed pulmonary eosinophilia. We
      conclude that B7-2 provides the necessary costimulatory signal required for the
      development of in vivo allergic responses to inhaled allergen exposure.

PMID- 9551946
TI  - Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new
      receptor protecting lymphocytes from the death ligand TRAIL.
AB  - Apoptosis can be triggered by the engagement of cell surface receptors by their
      ligands. A growing number of receptors belonging to the TNF receptor family have
      been identified that contain a conserved cytoplasmic death domain. These include
      Fas, TNF-R1, lymphocyte-associated receptor of death (LARD), DR4, and TNF-related
      apoptosis-inducing ligand receptor inducer of cell killing-2 (TRICK2). The latter
      two are receptors for the cytotoxic ligand TNF-related apoptosis-inducing ligand
      (TRAIL), and one of the paradoxes raised by the cloning of these molecules was
      why do most cells not die upon contact with the widely expressed TRAIL molecule?
      This is a particular problem for lymphocytes that express DR4 and TRICK2 and are
      in constant circulation through TRAIL-expressing tissues. We have cloned LIT
      (lymphocyte inhibitor of TRAIL), which lacks a death domain. LIT is expressed
      predominantly on PBL, where it can competitively inhibit TRAIL-induced apoptosis
      through DR4/TRICK2, and may function to modulate lymphocyte sensitivity to TRAIL.

PMID- 9551947
TI  - p21-activated kinase (PAK) is required for Fas-induced JNK activation in Jurkat
      cells.
AB  - The process of apoptosis is a critical component of normal immune system
      development and homeostasis, and in many cells this involves signaling through
      the c-Jun amino terminal kinase (JNK) pathway. In Jurkat T cells, Fas-induced JNK
      activity is dependent upon activation of the caspase cascades known to be central
      components of the apoptotic program. We show in Jurkat cell lines expressing a
      dominant negative PAK construct that PAK signaling is necessary for JNK
      activation in response to Fas receptor cross-linking. Inhibition of JNK
      activation induced by Fas does not impair cell death as assessed by DNA
      fragmentation. However, expression of the catalytically active C terminus of
      PAK2, which is generated through caspase action during Fas-mediated apoptosis,
      induces Jurkat cell apoptosis. We conclude that PAK activity resulting from
      caspase-mediated cleavage is a necessary component of JNK activation induced by
      Fas receptor signaling and that PAK2 can contribute to the induction of cell
      death.

PMID- 9551948
TI  - CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that
      inhibits interleukin-2 secretion but allows Bcl-X(L) induction.
AB  - We have assessed the functional effects of a panel of CTLA-4 mAbs on resting
      human CD4+ T cells. Our results demonstrate that some CTLA-4 mAbs can inhibit
      proliferative responses of resting CD4+ cells and cell cycle transition from G0
      to G1. The inhibitory effects of CTLA-4 were evident within 4 h, at a time when
      cell surface CTLA-4 expression remained undetectable. Other CTLA-4 mAbs had no
      detectable inhibitory effects, indicating that binding of Ab to CTLA-4 alone is
      not sufficient to mediate down-regulation of T cell responses. Interestingly,
      while IL-2 production was shut off, inhibitory anti-CTLA-4 mAbs permitted
      induction and expression of the cell survival gene bcl-X(L). Consistent with this
      observation, cells remained viable and apoptosis was not detected after CTLA-4
      ligation.

PMID- 9551949
TI  - Critical role of NK1+ T cells in IL-12-induced immune responses in vivo.
AB  - CD1-dependent NK1+ T cells rapidly produce IL-4 upon stimulation through the TCR.
      These cells may therefore play an important role in the initiation of Th2
      responses. Here, we show that NK1+ T cells constitutively express receptors for
      IL-12 and IFN-gamma, and that IL-12 induces production of perforin in these
      cells. Moreover, while IL-12 induces high levels of IFN-gamma and cytotoxic
      activity of hepatic or splenic mononuclear cells against tumor cells, this effect
      of IL-12 is significantly reduced in CD1-deficient mice with impaired NK1+ T
      cells development. These results indicate that NK1+ T cells play a critical role
      in IL-12-induced production of IFN-gamma to initiate Th1 immune responses and as
      IL-12-induced cytotoxic effector cells to initiate antitumor immunity.

PMID- 9551950
TI  - Identification of the mouse IgG3 receptor: implications for antibody effector
      function at the interface between innate and adaptive immunity.
AB  - Mouse IgG3 appears early in immune responses independently of T cell help and, as
      such, is an early effector molecule of the immune system. Yet, a specific IgG3
      cellular receptor remains undefined. In transfection experiments, mouse Fc
      gammaRI was clearly able to bind immune complexes of IgG3, whereas mouse Fc
      gammaRII could not. Furthermore, macrophages from mice expressing Fc gammaRII and
      Fc gammaRIII but lacking Fc gammaRI were unable to phagocytose IgG3 immune
      complexes, thus identifying mouse Fc gammaRI as the sole receptor for IgG3 immune
      complexes. Competition studies demonstrated that monomeric mouse IgG3 could
      inhibit IgG2a binding to mouse Fc gammaRI with an ID50 approximately 10(-7) M
      (fivefold lower than IgG2a). The identification of mouse Fc gammaRI as the IgG3
      receptor establishes Fc gammaRI as a participant in events at the interface
      between innate and adaptive immunity, implying a greater role for this receptor
      in the development of normal and pathologic immune responses than previously
      recognized.

PMID- 9551951
TI  - Stimulation of CD28 with B7-2 promotes focal adhesion-like cell contacts where
      Rho family small G proteins accumulate in T cells.
AB  - Unless a costimulatory signal is provided, TCR recognition of Ag bound to the MHC
      is insufficient to induce optimal T cell proliferation or the production of IL-2.
      Here we show that the stimulation of CD28, a T cell costimulatory receptor, by a
      specific Ab increases F-actin contents in T cells. The interaction between T
      cells and B7-2-transfected Chinese hamster ovary cells expressing the CD28 ligand
      leads to the rearrangement of the actin cytoskelton in the region of cell-cell
      contact. Within the Rho family of G proteins, Rac1, but not Rho, translocates to
      the sites of cell-cell contact where Tailin also accumulates. These results
      indicate that the interaction between B7-2 and CD28 establishes a focal adhesion
      like cell contact between T cell and APCs. The results also suggest that CD28
      signaling is primarily transduced by a cytoskeletal rearrangement/signaling
      pathway mediated by the Rho family G proteins.

PMID- 9551952
TI  - HIV-1 infection induces a selective reduction in STAT5 protein expression.
AB  - HIV-1 infection is accompanied by qualitative and quantitative defects in CD4+ T
      lymphocytes. Loss of immune function in HIV patients is usually associated with a
      profound dysregulation of cytokine production. To investigate whether cytokine
      signaling defects occur during HIV infection, PHA blasts from healthy human
      donors were infected with two strains of HIV-1 and screened for the expression of
      STAT proteins used in cytokine signaling. A selective decrease in STAT5B was seen
      8 days after infection with the BZ167 dual-tropic HIV isolate, but not with the
      Ba-L, M-tropic strain. Based on these findings, purified T cells from HIV
      infected patients in different stages of disease were also tested for STAT
      expression; decreases in STAT5A, STAT5B, and STAT1alpha were observed in all
      patients. The reduction in STATs seen in vivo and in vitro after HIV infection
      may contribute to the loss of T cell function in HIV disease.

PMID- 9551953
TI  - Differences between responses of naive and activated T cells to anergy induction.
AB  - T cell unresponsiveness to Ag stimulation can be induced by several means. The
      precise mechanism by which this process occurs remains poorly understood.
      Preincubating T cells with either EDCI-fixed APC or ionomycin is a proven means
      of inducing T cell anergy with reduced IL-2 production in response to Ag
      stimulation. Using T cells from mice expressing the TCR transgene DO11.10, which
      is specific for a peptide (323-339) derived from hen egg OVA, we demonstrate that
      naive cells obtained directly from the host are resistant to the anergy induction
      by either fixed APC or ionomycin. TCR transgenic mice also deficient in the
      recombination-activating gene-2 (RAG-2(-/-)), preventing the formation of T cells
      with endogenous TCRs, were immunized with OVA, and in vivo activated T cells with
      low expression of CD62 were isolated. These primed cells possess the same
      sensitivity to ionomycin-induced anergy as in vitro activated cell lines. This
      unresponsive state most profoundly affects Ag-induced IL-2 production, with IFN
      gamma and IL-3 affected to a lesser degree and no effect observed on IL-4
      production. Thus, T cells in vivo can be distinguished phenotypically by their
      susceptibility to anergic stimuli. Anergy so induced affects selected T cell
      functions.

PMID- 9551954
TI  - An alternative translational reading frame encodes an immunodominant retroviral
      CTL determinant expressed by an immunodeficiency-causing retrovirus.
AB  - Recognition of virus-infected or transformed cells by CD8+ CTL requires a
      trimolecular complex composed of MHC class I, beta2-microglobulin, and a specific
      foreign peptide composed of 8 to 10 linear amino acids. The generation of such
      CTL epitopes has traditionally been thought to be from the primary open reading
      frame encoding the viral or tumor-associated proteins. In this report it is
      demonstrated that a viral CTL epitope can also be generated from an alternative
      reading frame. Using a combination of synthetic peptides and Sindbis or vaccinia
      expression systems, MHC class I Kd-restricted BALB/cByJ CTL directed against
      defective gag gene constructs of the LP-BM5 virus complex that causes murine AIDS
      were shown to have specificity for the antigenic peptide SYNTGRFPPL. This epitope
      is generated in a novel fashion from the second open reading frame (ORF2) of both
      the defective and ecotropic helper virus components of LP-BM5. Importantly, lysis
      of target cells expressing BM5 ecotropic helper, and/or defective viral gag,
      demonstrated that the SYNTGRFPPL epitope is generated during the course of a
      normal retroviral infection. Furthermore, MAIDS-resistant BALB/cByJ mice also
      generated secondary restimulated CTL specific for SYNTGRFPPL following in vivo
      priming with the LP-BM5 retroviral complex. These data suggest that retroviruses,
      and potentially other viruses and foreign genes, are capable of expressing T cell
      epitopes from alternative open reading frames. If one considers the influence of
      self peptides on T cell development, these "alternative reading frame-derived"
      peptides could provide an important additional influence on the functional T cell
      repertoire.

PMID- 9551955
TI  - A new role for B cells in systemic autoimmunity: B cells promote spontaneous T
      cell activation in MRL-lpr/lpr mice.
AB  - A conventional view of the pathogenesis of systemic lupus erythematosus has
      emerged. The role of B cells is to secrete pathogenic autoantibodies, while the
      role of T cells is to provide help for autoantibody-producing B cells. A problem
      with this view is that spontaneous T cell activation as well as T cell
      infiltration of organs such as kidney and skin are prominent features in systemic
      lupus erythematosus patients and murine models of lupus. The identification of T
      cell infiltrates, in particular, suggests that autoantibody-mediated damage may
      be only part of the story and that T cells could also play a primary role in
      immune-mediated pathology. To test the role of B cells directly, we previously
      generated autoimmune-prone MRL-lpr/lpr mice that lack B cells. The complete
      absence of T cell infiltrates in these mice was surprising, and it prompted us to
      examine whether a key role of B cells in disease evolution is to prime
      autoreactive T cells. Here we demonstrate, by comparing B cell-deficient and
      control mice, that the expansion of activated and memory T cells in the MRL
      lpr/lpr mouse is indeed highly dependent on B cells. These results suggest a
      novel role for B cells in autoimmune disregulation.

PMID- 9551956
TI  - IL-4 induces eotaxin: a possible mechanism of selective eosinophil recruitment in
      helminth infection and atopy.
AB  - A common feature of some parasitic infections and allergic and atopic skin
      diseases is the involvement of Th2 lymphocytes and the dermal appearance of
      eosinophils (Eos). Because Th2 lymphocytes apparently do not release Eo
      attractants, we addressed the question of whether the Th2 cytokine IL-4 induces
      its production in dermal fibroblasts. We therefore stimulated fibroblasts with IL
      4. HPLC investigation of supernatants revealed a single Eo chemotactic protein,
      which was purified to homogeneity giving a single 13-kDa band upon SDS-PAGE
      analyses. Peptide mapping with subsequent amino acid sequencing revealed an Eo
      selective chemotaxin, which consists of a mixture of N-terminally truncated and O
      glycosylated forms of the chemokine eotaxin. Other chemokines such as RANTES, MCP
      3, MCP-4, or MIP-1alpha were not detected as Eo chemotaxins under these
      conditions. Using reverse transcriptase-PCR techniques, we found that IL-4 dose
      and time dependently induces eotaxin mRNA in dermal fibroblasts. Stimulation with
      IL-4 and TNF-alpha caused a 10- to 20-fold increase of the release of three
      biochemically different eotaxin forms, each consisting of a mixture of N
      terminally truncated and O-glycosylated variants having the same backbone amino
      acid sequence but different specific activities. Our findings support the
      hypothesis that eosinophil recruitment seen in IL-4-mediated skin reactions, at
      least in part, may be due to Th2 cytokine-mediated induction of eotaxin in dermal
      fibroblasts.

PMID- 9551957
TI  - In SCID-hu mice, passive transfer of a humanized antibody prevents infection and
      atrophic change of medulla in human thymic implant due to intravenous inoculation
      of primary HIV-1 isolate.
AB  - Using SCID-hu mice, it was tested whether humanized mAb Rmu5.5 could prevent
      infection by HIV-1 i.v. inoculation. The Ab that recognizes the IHIGPGRAFYT motif
      in the principal neutralizing determinant (PND) of HIV(MN), as well as the
      original mouse mAb mu5.5, neutralized HIV(MN) with high activity. Seven primary
      field isolates from Japanese hemophiliacs seropositive for HIV-1 clade B were
      compared for their reactivities to Rmu5.5. Rmu5.5 was effective, particularly
      against the viruses that matched amino acid sequences of the PND region of HIV-1,
      and it completely neutralized primary isolates. Moreover, the passive transfer of
      the Ab elicited protection against challenge by the primary isolates in SCID-hu
      or hu-PBL-SCID mice after i.v. inoculation with the virus by both quantitative
      PCR and PBMC-based virus isolation in vitro. Further, inoculation with the Ab
      also prevented the atrophic change in the medulla of the thymic transplant that
      was induced by i.v. inoculation of the virus. Thus, the humanized neutralizing Ab
      Rmu5.5 appears to protect SCID-hu mice from infection by primary field isolates.

PMID- 9551958
TI  - Naturally occurring low affinity peptide/MHC class I ligands can mediate negative
      selection and T cell activation.
AB  - The affinity/avidity model for T cell development postulates that ligands with
      high affinity for the TCR are efficient in negative selection, whereas those with
      lower affinity/avidity favor positive selection. Using the 2C TCR transgenic
      model, we evaluated the efficacy of ligands with widely differing affinity for
      the TCR (3 x 10(3) to 2 x 10(6) M(-1)) in mediating thymocyte deletion. The
      relative affinities of the 2C TCR for the p2Ca/Ld, dEV-8/Kb, p2Ca-A3/Ld, and
      p2Ca/Kb ligands are approximately 1000:50:10:1, respectively. Here we show, using
      an in vitro assay, that the deletion of 2C CD4+ CD8+ thymocytes is mediated not
      only by p2Ca/Ld, but also by the lower affinity ligands dEV-8/Kb, p2Ca-A3/Ld, and
      p2Ca/Kb, albeit at relatively higher peptide concentrations. Deletion mediated by
      low affinity ligands required CD8, whereas high affinity ligand-mediated deletion
      was CD8 independent. The p2Ca/Kb and dEV-8/Kb ligands are naturally occurring in
      H-2b mice, and others have shown that p2Ca/Kb can induce the maturation of CD4-
      CD8+ 2C-TCR(high) thymocytes in fetal thymic organ culture. In this study we
      showed that in addition to deletion, the p2Ca/Kb and dEV-8/Kb ligands, in the
      presence of exogenous IL-2, induced mature 2C T cell proliferation, albeit at a
      lower level than that induced by the high affinity p2Ca/Ld ligand. Thus, the same
      low affinity ligands that can effect negative selection and, in the case of
      p2Ca/Kb, the maturation of CD8 single-positive thymocytes can also induce the
      activation of mature CD8 T cells.

PMID- 9551959
TI  - Differential effects of the rejection of bone marrow allografts by the depletion
      of activating versus inhibiting Ly-49 natural killer cell subsets.
AB  - Natural killer cells mediate the specific rejection of bone marrow cell (BMC)
      allografts in lethally irradiated mice. The Ly-49 family of molecules present on
      subsets of murine NK cells appears capable of binding class I MHC molecules,
      resulting in transmission of an inhibitory signal to the NK cell. These Ly-49
      family members have been shown to have an immunoreceptor tyrosine-based
      inhibitory motif that is responsible for the inhibitory signal. However, a new Ly
      49 family member was found that lacks this motif, Ly-49D, and evidence suggests
      that this may be an activating receptor. We therefore compared the role of the
      activating Ly-49 member with NK cells bearing inhibitory Ly-49 receptors in BMC
      rejection. Depletion of Ly-49D+ NK cells in H-2b mice abrogated their ability to
      reject H-2d BMC allografts. Similarly, Ly-49C+ NK cells also were shown to
      mediate the specific rejection of H-2d BMC. When both subsets were depleted, an
      additive enhancement of BMC engraftment was observed, indicating that both
      subsets play a role in the rejection of allogeneic H-2-homozygous H-2d BMC.
      However, rejection of H-2(b x d) or D8 (H-2b, Dd transgene) BMC allografts was
      unaffected by Ly-49C+ NK cell depletion in H-2b mice. In marked contrast,
      depletion of Ly-49D+ NK cells in H-2b mice totally abrogated the rejection of H
      2(b x d) heterozygous BMC in support of in vitro data suggesting that Ly-49D+ NK
      cells receive activating signals. Therefore, NK subsets demonstrate a
      differential ability to reject H-2 homozygous and heterozygous BMC.

PMID- 9551960
TI  - Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells.
AB  - CTLA-4 has been proposed to negatively regulate immune responses, and mice
      deficient for CTLA-4 expression succumb to a lymphoproliferative disorder within
      a few weeks after birth. This study assessed the responsiveness of CTLA-4
      deficient T cells expressing a class I-restricted TCR specific for lymphocytic
      choriomeningitis virus (LCMV). The kinetics of T cell proliferation were studied
      in vitro after stimulation of T cells with full and partial T cell agonists. No
      gross abnormalities in CTLA-4-deficient T cells could be detected. Using adoptive
      transfer experiments, T cell responses were also measured in vivo after infection
      with LCMV. Low dose infection with LCMV leads to strong expansion of specific T
      cells followed by a reduction in T cells that parallels the elimination of Ag.
      The kinetics of T cell expansion and elimination after low dose LCMV infection
      were not affected by the absence of CTLA-4. High dose infection of mice with LCMV
      leads to a transient expansion of T cells followed by T cell exhaustion, where
      all specific T cells are eliminated. T cell exhaustion also occurred in the
      absence of CTLA-4. Thus, surprisingly, the absence of CTLA-4 did not interfere
      with T cell activation, down-regulation of ongoing T cell responses after the
      elimination of Ag, or the exhaustion of T cell responses in the presence of
      excessive amounts of Ag.

PMID- 9551961
TI  - Spontaneous inflammatory disease in HLA-B27 transgenic mice is independent of MHC
      class II molecules: a direct role for B27 heavy chains and not B27-derived
      peptides.
AB  - Although association of HLA-B27 with human spondyloarthropathies has been known
      for several years, its role in disease pathogenesis is not understood. Recently,
      a few investigators have proposed that presentation of B27-derived peptides by
      MHC class II molecules may be the underlying mechanism. HLA-B27 transgenic rat
      and mouse models have provided a new tool for understanding the exact role of B27
      in disease pathogenesis. HLA-B27 mice lacking endogenous beta2-microglobulin
      (B27+ beta2m(o)) develop disease after they are transferred from the barrier
      facility to the conventional colony. This model was utilized to test the
      hypothesis that B27-derived peptide presented by MHC class II molecules is the
      cause of the disease. The MHC class II knockout gene, A beta(o), was bred into
      our B27+ beta2m(o) mice, and disease manifestation was monitored. These mice
      develop spontaneous disease, demonstrating that MHC class II molecules do not
      play a major role in B27-related disease. Thus, the disease is not manifested by
      presentation of B27-derived peptides by class II molecules, since these mice are
      devoid of H2-A and H2-E molecules. Furthermore, in vivo treatment with mAb
      against the heavy chain of B27 reduced the incidence of disease in B27+ beta2m(o)
      mice. Our results clearly demonstrate that B27 heavy chains are directly involved
      in the disease process.

PMID- 9551962
TI  - Long-lived B cells are distinguished by elevated expression of A1.
AB  - Only 5% of the 15 million B cells formed daily reach the long-lived peripheral B
      cell pool, presumably reflecting both negative and positive selection. These
      selective events occur primarily during late stages of differentiation in the
      marrow and periphery, when newly formed B cells bear surface IgM (sIgM), but
      differ from mature B cells in their expression of heat-stable Ag (CD24), B220
      (CD45), and sIgD. Because genes of the Bcl-2 family influence longevity, we
      compared the expression of Bcl-2, Bax, and A1 among immature vs mature peripheral
      B cells using semiquantitative reverse-transcriptase PCR. While the levels of
      both Bcl-2 and Bax mRNA remain constant in these two populations, A1 expression
      is strikingly up-regulated among mature B cells. In addition, A1 expression is
      low among pro- and pre-B cells, as well as in immature (sIgM+) marrow B cells.
      Together, these data indicate that A1 mRNA expression is low at all stages of B
      cell development before final maturation in the periphery and, unlike other Bcl-2
      family members whose expression changes little after marrow egress, A1 is up
      regulated 10-fold as cells are recruited into the long-lived peripheral B cell
      pool.

PMID- 9551963
TI  - Post-thymic maturation of migrating human thymic single-positive T cells: thymic
      CD1a- CD4+ T cells are more susceptible to anergy induction by toxic shock
      syndrome toxin-1 than cord blood CD4+ T cells.
AB  - To determine whether human CD4+ T cells undergo post-thymic maturation, we
      compared the susceptibility to anergy induction in human thymic CD1a- CD4+ single
      positive (CD4+), cord blood (CB) CD4+, and adult peripheral blood (APB) CD4+ T
      cells by stimulation with toxic shock syndrome toxin-1 (TSST-1). Most TSST-1
      induced T cell blasts derived from either T cell preparation expressed TCR
      Vbeta2, which determines the potential reactivity to TSST-1. Most thymic CD4+ T
      cell blast preparations exhibited little or no production of IL-2 and IL-4 after
      restimulation with TSST-1 and only marginal responses after stimulation with rIL
      2 or a combination of PMA and calcium ionophore, while the APB CD4+ T cell blasts
      showed high responses to these stimuli. The responses of CB CD4+ T cell blasts to
      these stimuli varied, ranging from minimal to relatively high. Studies of DNA
      fragmentation showed that there was no significant cell death of thymic CD4+ T
      cell blasts. Most thymic CD1a- CD4+ and CB CD4+ T cells were CD38 positive. APB
      CD4+ T cell blasts derived from the CD38+ fraction and from the CD38- fraction
      exhibited equally high responses to restimulation with TSST-1. These results
      indicate that thymic CD1a- CD4+ and CB CD4+ T cells are inherently highly
      susceptible to anergy induction by bacterial superantigens and that thymic CD1a-
      CD4+ T cells are less mature than CB CD4+ T cells, suggesting that post-thymic
      maturation in thymic T cells migrating to the periphery is required for
      acquisition of full reactivity to antigenic stimulation.

PMID- 9551964
TI  - TNF receptor-deficient mice reveal striking differences between several models of
      thymocyte negative selection.
AB  - Central tolerance depends upon Ag-mediated cell death in developing thymocytes.
      However, the mechanism of induced death is poorly understood. Among the known
      death-inducing proteins, TNF was previously found to be constitutively expressed
      in the thymus. The role of TNF in thymocyte negative selection was therefore
      investigated using TNF receptor (TNFR)-deficient mice containing a TCR transgene.
      TNFR-deficient mice displayed aberrant negative selection in two models: an in
      vitro system in which APC are cultured with thymocytes, and a popular in vivo
      system in which mice are treated with anti-CD3 Abs. In contrast, TNFR-deficient
      mice displayed normal thymocyte deletion in two Ag-induced in vivo models of
      negative selection. Current models of negative selection and the role of TNFR
      family members in this process are discussed in light of these results.

PMID- 9551965
TI  - The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in
      Jurkat cells by up-regulating Fas ligand expression.
AB  - T lymphocytes undergo apoptosis in response to cellular stress, including UV
      exposure and gamma irradiation. However, the mechanism by which stress stimuli
      induce apoptosis is not well understood. While stress stimuli induce the
      activation of the c-Jun N-terminal kinase (JNK) pathway, it is not clear whether
      the JNK cascade is activated as a result of cell death or whether the cascade
      participates in inducing apoptosis. Using a Jurkat T cell line transfected with
      dominant active (DA)-mitogen-activated protein kinase kinase kinase (MEKK1) in a
      tetracycline-regulated expression system, we found that expression of DA-MEKK1
      results in the apoptosis of Jurkat cells in parallel with prolonged JNK
      activation. Moreover, DA-MEKK1 induced Fas ligand (FasL) cell surface and mRNA
      expression, as well as FasL promoter activation. Interference with Fas/FasL
      interaction prevented DA-MEKK1-mediated apoptosis. In comparing the effect of
      different stress stimuli to DA-MEKK1, we found that UV, gamma irradiation, and
      anisomycin prolonged JNK activation in parallel with FasL expression and onset of
      cell death. In addition, these stimuli also enhance cell surface expression of
      FasL. Interference with Fas/FasL interactions inhibited anisomycin but not UV- or
      gamma irradiation-induced apoptosis. Our data show that while the JNK pathway
      contributes to stress-induced apoptosis in T lymphocytes by regulating FasL
      expression, not all stress stimuli use the same cell death pathway.

PMID- 9551966
TI  - Harnessing Syk family tyrosine kinases as signaling domains for chimeric single
      chain of the variable domain receptors: optimal design for T cell activation.
AB  - T cells of tumor bearers often show defective TCR-mediated signaling events and,
      therefore, exhibit impaired immune responses. As such, patients with heavy tumor
      burden are often not amenable to adoptive T cell therapy. To overcome this
      limitation, we have developed a chimeric receptor that joins an extracellular
      single chain Fv (scFv) of a specific Ab for Ag recognition to an intracellular
      protein tyrosine kinase (PTK) for signal propagation. Stimulation through the
      scFv-PTK receptor should bypass defective TCR-proximal events and directly access
      the T cell's effector mechanisms. In this study we describe the optimization of a
      scFv-PTK configuration, leading to complete T cell activation. The cytosolic PTK
      Syk is superior to its family member, Zap-70, for intracellular signaling. As a
      transmembrane (TM) domain, CD4 performs better than CD8 when plastic-immobilized
      Ag serves as a stimulator. However, when APC are used to trigger chimeric
      receptors, the need for a flexible spacer between the scFv and TM domains becomes
      apparent. The CD8alpha-derived hinge successfully performs this task in chimeric
      scFv-Syk receptors regardless of its cysteine content. A cytotoxic T cell
      hybridoma expressing chimeric receptor genes composed of scFv-CD8(hinge)-CD8(TM)
      Syk or scFv-CD8(hinge)-CD4(TM)-Syk is efficiently stimulated to produce IL-2 upon
      interaction with APC and specifically lyses appropriate target cells in a non-MHC
      restricted manner.

PMID- 9551967
TI  - Induction of granulomatous experimental autoimmune thyroiditis in IL-4 gene
      disrupted mice.
AB  - To study the role of IL-4 in development of granulomatous experimental autoimmune
      thyroiditis (EAT), IL-4 gene-disrupted mice expressing the EAT-susceptible H-2k
      haplotype were generated and used for EAT induction. Spleen cells from mouse
      thyroglobulin (MTg) and LPS-primed IL-4(+/+) and IL-4(-/-) donors could induce
      severe granulomatous EAT when spleen cells were activated with MTg and anti-IL-2R
      mAb in the presence of IL-12. Thyroid lesions had extensive follicular cell
      proliferation, large numbers of histiocytes, polymorphonuclear leukocytes, and
      multinucleated giant cells, in addition to lymphocytes and other mononuclear
      cells. Expression of IFN-gamma gene mRNA and production of IFN-gamma by effector
      spleen cells stimulated with MTg and IL-12 were similar for both IL-4(+/+) and IL
      4(-/-) mice. Although IL-4 was undetectable in IL-4(-/-) mice, expression of mRNA
      for IL-5, IL-10, and IL-13 and production of IL-5 by both MTg-activated spleen
      cells and anti-CD3-activated CD4+ T cells were comparable for cells from IL
      4(+/+) and IL-4(-/-) mice, indicating that the absence of IL-4 did not prevent
      production of other Th2 cytokines. Production of MTg-specific IgG1 was very low
      or undetectable in IL-4(-/-) mice. IL-4 gene mRNA and MTg-specific IgG1 could be
      detected in IL-4(+/+) or IL-4(-/-) recipients only when they received effector
      cells from IL-4(+/+) donor mice, indicating that IL-4- and IgG1-secreting cells
      are of donor origin. These results demonstrate that IL-4 is not essential for
      development of granulomatous EAT.

PMID- 9551968
TI  - Regulation of TCR signal transduction in murine thymocytes by multiple TCR zeta
      chain signaling motifs.
AB  - The alphabeta TCR is a multimeric protein complex comprising ligand-binding and
      signal-transducing subunits. The signal transduction processes are mediated by
      the immunoreceptor tyrosine-based activation motifs (ITAMs), and up to 10 ITAMs
      are present within a single TCR complex. This multiplicity may allow for signal
      amplification and/or the formation of qualitatively distinct intracellular
      signals. Notably, the TCR-zeta subunit contains three ITAMs, and exists as a
      disulfide-linked homodimer in the TCR complex. In normal murine thymocytes and
      peripheral T cells, a proportion of TCR-zeta molecules is constitutively tyrosine
      phosphorylated and associated with the ZAP-70 protein tyrosine kinase. We
      examined the contribution of the different TCR-zeta ITAMs in regulating the
      constitutive phosphorylation of the TCR-zeta subunit in thymocytes by analyzing
      TCR-zeta-deficient mice that had been reconstituted with either full-length or
      single ITAM-containing TCR-zeta subunits. We report in this work that in the
      absence of a full-length TCR-zeta subunit, there is no apparent constitutive
      phosphorylation of the remaining TCR/CD3 ITAMs. Following TCR ligation, all of
      the CD3 ITAMs become inducibly phosphorylated and associate with the ZAP-70
      protein tyrosine kinase. Regardless of the number of TCR-zeta ITAMs present in
      the TCR complex, we report that a number of molecules involved in downstream
      signaling events, such as ZAP-70, SLP-76, and pp36, are all inducibly tyrosine
      phosphorylated following TCR ligation. These results support the notion that the
      different TCR ITAMs function in a quantitative rather than qualitative manner.

PMID- 9551969
TI  - Reduced cell surface expression of HLA-C molecules correlates with restricted
      peptide binding and stable TAP interaction.
AB  - HLA-C molecules are poorly expressed at the cell surface compared with HLA-A and
      HLA-B locus products. The reason for the low surface expression and the
      underlying mechanism is unclear. We show that the HLA-C4 allele is expressed
      intracellularly in amounts similar to HLA-A and HLA-B alleles. However, the
      majority of the HLA-C4 molecules is not transported, but is retained in the
      endoplasmic reticulum by stable interaction with TAP. This pool does not appear
      to participate in the formation of HLA-C4/peptide complexes, but is degraded in
      the endoplasmic reticulum. HLA-C4 molecules can dissociate from TAP upon binding
      of specific peptide. However, they require a 10-fold higher concentration of a
      completely degenerated 9-mer peptide mixture for release from TAP than the HLA-A
      and HLA-B alleles. Our data show that the HLA-C molecules tested are more
      selective in their peptide binding than HLA-A and HLA-B molecules, resulting in
      prolonged association with TAP and a reduced formation of intracellular HLA
      C/peptide complexes. The restricted peptide binding of certain HLA-C alleles
      provides one explanation for the reduced expression of HLA-C molecules at the
      cell surface. Other mechanisms will be discussed.

PMID- 9551970
TI  - Detection and delineation of CXCR-4 (fusin) as an entry and fusion cofactor for T
      tropic [correction of T cell-tropic] HIV-1 by three different monoclonal
      antibodies.
AB  - A chemokine receptor, CXCR-4, has been identified as an entry cofactor for T cell
      line-tropic (T-tropic) HIV-1. To detect expression of CXCR-4 at the single cell
      level and dissect postbinding events of HIV-1 infection, we generated three mAbs
      against human CXCR-4. These mAbs inhibited SDF-1-induced intracellular Ca2+
      mobilization, and one of the mAbs immunoprecipitated a specific 47-kDa component
      from CXCR-4+ cells. Flow cytometric analysis showed that most human cell lines
      examined expressed CXCR-4. A fraction of normal PBMC expressed CXCR-4, but
      neutrophils were negative. Two-color analysis revealed that the majority of T
      cells, virtually all B cells, and all monocytes expressed CXCR-4, while it was
      only weakly present on NK cells. Thus, expression of CXCR-4 is not ubiquitous but
      cell type specific in hemopoietic cells. The three mAbs were shown to suppress
      cell fusion mediated by envelope proteins of a T-tropic NL432 virus but not by
      those of an M-tropic JRCSF virus Likewise, they suppressed infection of NL432 but
      not that of an M-tropic NL162 virus. In both cases it was noted that the
      suppressive activity varied considerably among the mAbs. These data confirmed
      that CXCR-4 is directly involved in env-mediated entry and fusion of T-tropic HIV
      1 and suggest that the epitopes on CXCR-4 recognized by the three mAbs may have
      different roles in interaction with the envelope proteins of T-tropic HIV-1.

PMID- 9551971
TI  - The MHC-E locus is the most well conserved of all known primate class I
      histocompatibility genes.
AB  - The HLA-E locus is characterized by limited polymorphism and low levels of cell
      surface expression. However, the function of the products of this nonclassical
      MHC class I gene remains unknown. To evaluate the conservation of the MHC-E locus
      throughout anthropoid primate evolution, we identified the homologue of the HLA-E
      locus in six different New World monkey species. Full-length sequencing of MHC
      EcDNAs in four unrelated cotton-top tamarins (Saguinus oedipus) revealed no
      evidence for polymorphism. Using the PCR, denaturing gradient gel
      electrophoresis, and direct sequencing, we also identified MHC-E alleles in five
      other New World monkey species, representing all extant platyrrhine families. In
      contrast to all other classical and nonclassical MHC class I genes in primates,
      the rate of synonymous nucleotide substitution is much greater than the rate of
      nonsynonymous nucleotide substitution within exons 2 and 3 encoding the peptide
      binding region (PBR) in MHC-E genes. The PBR of the MHC-E molecule, therefore,
      has evolved under purifying selective pressures, and the very unusual
      evolutionary history of this ancient gene provides further evidence that the
      products of the HLA-E locus serve a critical immunological function. Given the
      remarkable conservation of the PBR during primate evolution, this critical
      immunological function is probably related to the peptide binding ability of the
      MHC-E protein.

PMID- 9551972
TI  - Characterization and mapping to human chromosome 8q24.3 of Ly-6-related gene 9804
      encoding an apparent homologue of mouse TSA-1.
AB  - The 9804 gene, which encodes a human Ly-6 protein most similar to mouse
      differentiation Ag TSA-1/Sca-2, has also been called RIG-E. Like mouse TSA-1, it
      has a broad tissue distribution with varied expression levels in normal human
      tissues and tumor cell lines. Like some members of the murine Ly-6 family, the
      9804 gene is responsive to IFNs, particularly IFN-alpha. Overlapping genomic
      fragments spanning the 9804 gene (5543 bp) have been isolated and characterized.
      The gene organization is analogous to that of known mouse Ly-6 genes. The first
      exon, 2296 bp upstream from exon II, is entirely untranslated. The three coding
      exons (II, III, and IV) are separated by short introns of 321 and 131 bp,
      respectively. Primers were developed for specific amplification of 9804 gene
      fragments. Screening of human-hamster somatic cell hybrids and yeast artificial
      chromosomes (YACs) indicated that the gene is distal to c-Myc, located in the q
      arm of human chromosome 8. No positives were detected from the Centre d'Etude du
      Polymorphisme Humain mega-YAC A or B panels, nor from bacterial artificial
      chromosome libraries; two positive cosmids (c101F1 and c157F6) were isolated from
      a human chromosome 8 cosmid library (LA08NC01). Fluorescence in situ
      hybridization of metaphase spreads of chromosome 8, containing hybrid cell line
      706-B6 clone 17 (CL-17) with cosmid c101F1, placed the 9804 gene close to the
      telomere at 8q24.3. This mapping is significant, since the region shares a
      homology with a portion of mouse chromosome 15, which extends into band E where
      Ly-6 genes reside. Moreover, the gene encoding E48, the homologue of mouse Ly-6
      molecule ThB, has also been mapped to 8q24.

PMID- 9551973
TI  - Nuclear factor of activated T cells (NFAT) as a molecular target for 1alpha,25
      dihydroxyvitamin D3-mediated effects.
AB  - The molecular basis of the immunomodulatory properties of 1alpha,25
      dihydroxyvitamin D3 (1alpha,25(OH)2D3) remains elusive. We demonstrate here that
      1alpha,25(OH)2D3-mediated suppressive effects on the inducible expression of
      cytokine genes in human T cells may, in part, be due to diminished activity of
      the transcription factor NFAT. The vitamin D3 receptor (VDR) and its
      heterodimeric partner retinoid X receptor alpha (RXR alpha) specifically bound to
      the distal NFAT site in the human IL-2 promoter, and this binding was abolished
      by mutating unique regions in the NFAT oligonucleotide. In vitro inhibition of
      NFAT complex formation was noted when VDR-RXR alpha heterodimers were added to
      DNA binding reactions containing nuclear extracts from activated B or T cells,
      whereas in vitro NFkappaB complex formation was not significantly influenced.
      Furthermore, 1alpha,25(OH)2D3 treatment of activated T cells resulted in
      decreased formation of NFAT complexes detected upon incubation of nuclear
      extracts from these cells with 32P-labeled probe. Transient expression of both
      VDR and RXR alpha, but not of a single component, was capable of inhibiting
      expression of a NFAT-driven reporter gene in stimulated jurkat cells in a ligand
      dependent manner. These results suggest that NFAT plays a crucial role in
      1alpha,25(OH)2D3-mediated immunosuppressive activity.

PMID- 9551974
TI  - Identification of an inhibitory MHC receptor on alloreactive rat natural killer
      cells.
AB  - Studies of allogeneic lymphocyte cytotoxicity have shown that the rat NK
      allorecognition repertoire is controlled by genetic elements in both the MHC
      (RT1) and the NK gene complex (NKC). DA rats, possessing NK cells that are unable
      to lyse allogeneic lymphoblasts, were immunized with alloreactive NK cells from
      MHC-matched PVG.1AV1 rats, and two mAb, STOK1 and STOK2, were generated. STOK1
      and STOK2 stained identical subsets of NKR-P1+ T and NK cells from certain
      strains of rats. Relative numbers varied markedly in a panel of MHC congenic
      strains, however, implicating a role for self MHC genes in their development.
      Both STOK1 and STOK2 immunoprecipitated a 110-kDa disulfide-linked homodimeric
      molecule, with extensive N-linked glycosylations, encoded by a gene that mapped
      to the NKC. NK cells expressing this glycoprotein displayed an increased ability
      to lyse allogeneic lymphoblasts, while syngeneic targets were spared. However,
      blockade of the STOK2 Ag with F(ab')2 of STOK2 permitted the NK lysis of
      syngeneic targets, but did not affect NK allorecognition. These results indicate
      that mAb STOK1 and STOK2 identify an NKC-encoded MHC receptor in the rat that
      acts as a negative regulator of cytotoxicity.

PMID- 9551975
TI  - Staphylococcal enterotoxin D is a promiscuous superantigen offering multiple
      modes of interactions with the MHC class II receptors.
AB  - Dimerization of MHC class II molecules on the cell surface of human THP-1
      monocytic cell line is a requirement for staphylococcal superantigen (SAG)
      induced cytokine gene expression. The capacities of various SAG to induce this
      response are governed by their modes of interaction with MHC class II molecules.
      Staphylococcal enterotoxin A (SEA), with its two binding sites, dimerizes MHC
      class II molecules and subsequently induces cytokine gene expression in THP-1
      cells. Here, we demonstrate that staphylococcal enterotoxin D (SED) and
      staphylococcal enterotoxin E (SEE) induce, similarly, IL-1beta and TNF-alpha gene
      expression in these cells. Using mutated toxins that lost their binding site with
      the MHC class II alpha- or beta-chain, we demonstrate that this response is also
      mediated by the dimerization of MHC class II molecules through two binding sites.
      Furthermore, SED forms Zn2+-dependent homodimers that allow multiple modes of MHC
      class II clustering, including ligation of alpha-chains (alpha/alpha), beta
      chains (beta/beta), or the alpha- and beta-chains of two different class II
      molecules. The beta/beta interaction following Zn2+-dependent SED/SED homodimer
      formation seems to be mediated by the appearance of a novel binding site on SED
      that interacts with histidine 81 of the MHC class II beta-chain. The different
      modes of SED interactions also influence SED-induced T cell activation where
      simultaneous ligation of the alpha- and beta-chains is essential for optimal
      response. These various modes of SED binding may be used to preserve bivalency
      regardless of variability in the MHC class II alpha/beta/peptide complexes.

PMID- 9551976
TI  - Identification of distinct regions of 5' flanking DNA that mediate constitutive,
      IFN-gamma, STAT1, and TGF-beta-regulated expression of the class II
      transactivator gene.
AB  - Class II transactivator (CIITA) is a master regulator required for constitutive
      and IFN-gamma-inducible expression of class II MHC genes. Although the role of
      CIITA is greatly appreciated, the mechanisms underlying constitutive and IFN
      gamma-induced expression of CIITA are not understood. The study of CIITA
      induction is extremely important, but has been fraught with difficulty. This
      study describes for the first time a large (7-kb) fragment of 5' flanking
      sequences that mediates the B cell-specific, IFN-gamma-induced, and TGF-beta
      suppressed expression of CIITA. This pattern of expression matches the authentic
      expression of the endogenous gene. Within the 7-kb fragment, sequences that lie
      between nucleotides -545 and -113 relative to the transcriptional start site are
      critical for constitutive promoter expression in B cells. In contrast, inducible
      activation of CIITA by IFN-gamma requires sequences contained in an additional 4
      kb of upstream DNA. This region mediates an IFN-gamma response when linked to
      either the endogenous CIITA promoter or a heterologous promoter. A role for STAT1
      in regulation of the CIITA promoter is shown by the rescue of IFN-gamma induction
      by expression of STAT1 in STAT1-defective U3A cells. TGF-beta significantly
      inhibits IFN-gamma-mediated induction of the CIITA promoter in 2fTGH fibroblasts,
      which indicates that the promoter is a target for TGF-beta. This inhibition is
      achieved by suppression of the basal promoter. This study provides a focal point
      for understanding the mechanism of B cell-specific, IFN-gamma-induced, and TGF
      beta-suppressed expression of CIITA.

PMID- 9551977
TI  - A two-step mechanism for recruitment of Pip by PU.1.
AB  - Transcription of the Ig kappa light chain gene is controlled in part by the 3'
      kappa enhancer. Two of the proteins that bind to the 3' enhancer, PU.1 and Pip,
      show tissue-restricted expression and may be responsible for the tissue
      specificity of 3' enhancer activity. PU.1 alone can bind to DNA; however, Pip
      cannot bind to its 3' enhancer site in electrophoretic mobility shift assays,
      unless recruited by PU.1. Previously, we showed that the PU.1 PEST domain (rich
      in the amino acids proline, glutamate, serine, and threonine; sequences 118-160)
      is necessary for Pip recruitment to DNA. Here we used detailed mutagenic analyzes
      of PU.1 to more precisely identify sequences required for Pip recruitment by
      electrophoretic mobility shift assay. We found that mutation of three segments
      within the PU.1 PEST domain (118-125, 133-139, and 141-147) modulated the
      efficiency of Pip recruitment, while mutation of sequences between residues 88
      118 and 154-168 had no effect. Interestingly, we found that the PU.1 ETS domain
      (residues 170 to 255) is both necessary and sufficient for Pip interaction in
      solution and that other ETS domain proteins can physically interact with Pip as
      well. Our results suggest that Pip recruitment to DNA by PU.1 occurs via a two
      step mechanism. First, a physical interaction that is not sufficient to recruit
      Pip occurs via the PU.1 ETS domain. Second, a conformational change in the PU.1
      PEST domain, apparently mediated by serine phosphorylation, induces a
      conformational change in Pip enabling it to bind to DNA. We also show that the
      PU.1 PEST domain does not target PU.1 for rapid turnover.

PMID- 9551978
TI  - Monoclonal anti-cardiolipin antibodies from New Zealand Black x New Zealand White
      F1 mice react to thrombomodulin.
AB  - The reactivity with and affinity for thrombomodulin (TM) of monoclonal anti
      cardiolipin Abs (MoaCL), derived from a New Zealand Black x New Zealand White F1
      (NZB/W F1) mouse, were studied to investigate the pathogenicity of anti
      cardiolipin Abs (aCL). Four of eighteen MoaCL were found to react with rabbit TM
      when examined using ELISA. These four MoaCL also reacted with synthetic peptide
      that included the epidermal growth factor-like domain of human TM, a binding site
      for thrombin. The reaction with TM of these four MoaCL was inhibited by bovine
      thrombin. When the affinity for TM of the MoaCL was determined, the dissociation
      constants (Kd) ranged from 4.8 x 10(-9) to 4.7 x 10(-8) M. By contrast,
      examination of the affinity for cardiolipin (CL) gave values from 8.3 x 10(-6) to
      7.4 x 10(-5) M. Thus, these MoaCL reacted to TM with a higher affinity than to
      CL. Moreover, these MoaCL also bound to TM on HUVEC and down-regulated the
      expression level of TM on the surface of HUVEC due to internalization of TM. The
      binding of thrombin to TM is known to initiate rapid protein C activation, and
      complexes of activated protein C and protein S show anticoagulatory activity.
      Thus, the present studies suggest that certain pathogenic aCL cross-react with TM
      and induce down-regulation of TM on endothelial cells, followed by induction of
      thrombosis.

PMID- 9551979
TI  - V(H) repertoire of a marsupial (Monodelphis domestica).
AB  - When contrasted with information available for placental mammals, very little is
      known about the development of immunocompetence in marsupials. Marsupials,
      however, provide interesting immunology problems, since most appear to be born at
      a stage of development much less mature than that of placental mammals. To
      further understand the marsupial immune system, the Ig repertoire of the short
      tailed opossum, Monodelphis domestica, was characterized. The majority of the
      V(H) clones were isolated in an unbiased manner by screening a spleen cDNA phage
      library, using C region probes, or anchored PCR, using C region-specific primers
      paired with vector specific primers. Analysis of 54 unique V(H) sequences from
      this marsupial revealed the presence of two V(H) families in the expressed Ig
      repertoire. The larger family, which contributed the majority of the clones
      identified, appears to be derived from 10 to 12 germline V(H) segments. The
      second family of clones is derived from a single germline V(H). Both V(H)
      families are related to the group III sequences described in other vertebrates.
      Unusual codon bias differences between the two families may result in very
      different patterns of somatic mutation within the opossum Ig repertoire.

PMID- 9551980
TI  - Molecular analysis of the major MHC recombinational hot spot located within the
      G7c gene of the murine class III region that is involved in disease
      susceptibility.
AB  - Recombination within the MHC does not occur at random, but crossovers are
      clustered in hot spots. We previously described a recombinational hotspot within
      the 50-kb Hsp70.3-G7 interval in the class III region of the mouse MHC. The
      parental haplotypes of recombinants with crossovers in this region represent the
      majority of the laboratory haplotypes (a, b, d, dx, k, m, p, px, q, s, and u).
      Using microsatellite markers and sequence-based nucleotide polymorphisms, the
      breakpoint intervals of 30 recombinants were mapped to a 5-kb-long interval
      within the G7c gene adjacent to G7a. Recombination within the G7c hot spot does
      not appear to be restricted to certain haplotypes. Sequence motifs that had been
      suggested to be associated with site-restricted meiotic recombination were absent
      in the vicinity of the G7c hot spot, and hence, these sequence motifs are no
      prerequisite for meiotic recombination. The G7c hot spot resides in a region to
      which a number of disease susceptibility loci have been mapped, including
      susceptibility to cleft palate, experimental autoimmune allergic orchitis, and
      chemically induced alveolar lung tumors. The exact localization of crossovers in
      recombinants that have been used in functional studies is important for mapping
      susceptibility genes and limits the number of candidate genes.

PMID- 9551981
TI  - Common and distinct signaling pathways mediate the induction of TNF-alpha and IL
      5 in IgE plus antigen-stimulated mast cells.
AB  - A small number of signaling cascades represented by mitogen-activated protein
      kinases, phosphoinositol-3-kinase, protein kinase C, signal transducers and
      activators of transcription, Ca2+/calcineurin, and a few other molecules are
      linked to an incomparably large number of surface receptors. Parallel activation
      of several of these pathways and the existence of isozymes for a number of signal
      transmitting molecules generate the required complexity and specificity matching
      the receptor variety. Here we show that the proinflammatory mediator TNF-alpha
      and the growth factor IL-5 are activated along common and distinct signaling
      cascades in allergically stimulated murine mast cells. Both of them are dependent
      on Ca2+ influx, activation of calcineurin and nuclear factor of activated T cells
      as well as a member of the atypical PKC family, most likely PKCmu. Additionally,
      mitogen-activated protein kinases for TNF-alpha and members of the classical or
      nonclassical PKCs for IL-5, respectively, were identified as additional required
      pathways. Inhibition of the classical and nonclassical PKCs, however, does not
      abrogate IL-5 induction but instead leads to a switch to mitogen-activated
      protein kinases, which then become essential. The activated branches of this
      "salvage" signaling cascade are represented by extracellular signal-regulated
      kinase 1/2 and c-jun NH2 terminal kinase 1 in allergically stimulated mast cells.

PMID- 9551982
TI  - The role of recombinant murine IL-12 and IFN-gamma in the pathogenesis of a
      murine systemic Candida albicans infection.
AB  - Studies on murine candidiasis suggest that resistance to disease is linked to a
      Th1 response and production of IFN-gamma, while failure to elicit protection is
      associated with a Th2 response and production of IL-4 and IL-10. Experimental
      infection of C57BL/6 mice, IL-12 treatment of these mice, or both infection and
      IL-12 treatment resulted in a characteristic Th1 cytokine mRNA profile as
      measured by quantitative competitive PCR. Specifically, little or no IL-4
      transcripts were detected, while IFN-gamma message was elevated, particularly
      with IL-12 treatment. Despite its role in driving increased IFN-gamma expression
      and production, IL-12 treatment, paradoxically, promoted disease progression in
      our model. Therefore, we examined the effect of IFN-gamma neutralization on IL-12
      induced susceptibility to infection. None of the systemically infected mice
      receiving IL-12 alone survived, while IL-12- and anti-IFN-gamma-treated mice had
      a 70% survival rate, similar to that after infection alone. These results
      suggested that IFN-gamma induced by IL-12 treatment contributed to lethality.
      However, in separate studies, IFN-gamma knockout mice were more susceptible to
      infection than their wild-type counterparts, suggesting that IFN-gamma is
      required for resistance. Nonetheless, infected IFN-gamma knockout mice treated
      with recombinant murine IL-12 exhibited enhanced resistance, suggesting that the
      toxicities observed with IL-12 are directly attributable to IFN-gamma and that an
      optimal immune response to Candida infections necessitates a finely tuned balance
      of IFN-gamma production. Thus, we propose that although IFN-gamma can drive
      resistance, the overproduction of IFN-gamma during candidiasis, mediated by IL-12
      administration, leads to enhanced susceptibility.

PMID- 9551983
TI  - Peptides that mimic the group B streptococcal type III capsular polysaccharide
      antigen.
AB  - Microbial polysaccharides are notably poor immunogens. We have developed an
      alternate route for the production of Abs to important carbohydrate epitopes. mAb
      S9, a protective mAb against the type III capsular polysaccharide of group B
      streptococci (GBS), was used to select epitope analogues from a peptide display
      phage library. Depending upon desorption conditions, two populations of phage
      were identified with displayed sequences of WENWMMGNA and FDTGAFDPDWPA. ELISA
      results demonstrated that these phage bound to S9 and no other Abs. Phage blocked
      the binding of S9 to type III GBS, but did not block binding by another anti-GBS
      mAb. Phage displaying the latter peptide sequence showed greater inhibition. Ab
      S9 and other monoclonal and polyclonal anti-GBS type III antisera bound the
      synthetic peptide FDTGAFDPDWPAC. The binding of S9 to GBS was inhibited by the
      free peptide with an IC50 of 30 microg/ml. The binding of polyclonal anti-GBS
      antibodies to peptide could be blocked by intact GBS as well as purified capsular
      polysaccharide. The peptide was conjugated to three different carriers and was
      used to immunize mice. All mice produced a significant antibody response to GBS
      and to the purified capsular polysaccharide following a single immunization.
      These data demonstrate that a peptide mimetic of the GBS capsular polysaccharide
      is both antigenic and immunogenic. The incorporation of such peptides into
      vaccine preparations may enhance the efficacy of vaccines in inducing Ab
      responses to important carbohydrate epitopes.

PMID- 9551984
TI  - IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and
      promotes resolution of, bacterial infection in mice.
AB  - IL-12-induced IFN-gamma production is essential for clearance of Yersinia
      enterocolitica infection. Similar to IL-12, the recently described cytokine IL-18
      (IFN-gamma-inducing factor) is produced by macrophages and induces IFN-gamma
      production in spleen cells. Therefore, we have investigated the role of IL-18 in
      Yersinia infection of mice. Heat-killed yersinia-triggered IL-18-promoted IFN
      gamma production of splenocytes was predominantly dependent on endogenous IL-12
      production, whereas IL-12-promoted IFN-gamma production was not IL-18 dependent.
      IL-18-induced IFN-gamma production was to a higher degree dependent on IFN-gammaR
      mediated mechanisms and in synergism with IL-2 resulted in at least fivefold
      higher IFN-gamma levels as compared with the combination of IL-12 plus IL-2.
      Analysis of the effect of IL-18 on IL-12 production of LPS-stimulated peritoneal
      macrophages revealed that IL-18 decreased LPS-induced IL-12 production,
      indicating that IL-18 might be involved in negative regulation of IL-12
      production. In vivo studies revealed that Yersinia-resistant C57BL/6 mice
      expressed fourfold higher IL-18 mRNA levels than did susceptible BALB/c mice.
      Administration of anti-IL-18 Abs caused a 100- to 1000-fold increase in bacterial
      counts in the spleen of infected mice but did not change IFN-gamma production
      levels. Taken together, our data demonstrate that IL-18 is involved in regulation
      of cytokine production during the early phase of bacterial infections as well as
      in clearance of Yersinia infection.

PMID- 9551985
TI  - Septic arthritis following Staphylococcus aureus infection in mice lacking
      inducible nitric oxide synthase.
AB  - Nitric oxide (NO), produced in large amounts by inducible NO synthase (iNOS), has
      emerged recently as an important microbicidal and immunomodulatory mediator. We
      have investigated its role in bacterial septic arthritis caused by Staphylococcus
      aureus infection using iNOS-deficient mice. The incidence, rate of development,
      and severity of arthritis were greater in iNOS-deficient than in heterozygous or
      wild-type control mice. Similarly, the incidence and severity of septicemia and
      mortality were significantly higher in iNOS-deficient mice compared with
      controls. Increased TNF-alpha synthesis in vivo and in vitro and enhanced IFN
      gamma compared with IL-4 production in vitro in iNOS-mutant mice demonstrated
      exaggerated Th1 polarization of the host response. These data indicate that high
      output NO production is not a prerequisite for severe articular destruction and
      imply that NO is of importance in synovial defense against staphylococcal
      infection.

PMID- 9551986
TI  - Legionella pneumophila infection in intratracheally inoculated T cell-depleted or
      -nondepleted A/J mice.
AB  - The inflammatory response and influence of T cell depletion on the pathogenesis
      of an experimental Legionella infection were studied. A/J mice were infected with
      10(6) CFU of Legionella pneumophila intratracheally. With this dose all infected
      animals survived the infection and bacteria were cleared from lung, spleen,
      liver, and kidney within 10 to 11 days, leaving no residual changes in the
      affected organs. Inflammatory cells were recruited into the lung on the second
      day of infection, reaching a maximum on the third day and filling out
      predominantly the interstitial areas. During the first 3 days after inoculation,
      mainly macrophages, B cells, NK cells, and large mononuclear cells of an unknown
      phenotype were attracted into the lung interstitium, whereas T lymphocytes
      infiltrated subsequently. During the early phase of infection, serum
      concentrations of IFN-gamma, TNF-alpha, IL-1beta, IL-4, and IL-6 but not IL-2
      increased dramatically. The cytokine secretion decreased on the third day after
      infection although bacteria were still present in the lung or even disseminated
      in different organs. Successful clearance of bacteria from the lung was not
      observed before recruitment of T cells into the lung. In mice depleted of both
      CD4+ and CD8+ T cells, control of infection was impaired and lethality of
      infection increased. Depletion of either subset left residual antibacterial
      mechanisms, which, however, were not sufficient to clear the Legionella as
      rapidly as in undepleted mice.

PMID- 9551987
TI  - Mechanism of protective immunity against influenza virus infection in mice
      without antibodies.
AB  - There is considerable interest in developing viral vaccines intended to induce T
      cell immunity, especially cytotoxic CD8+ T lymphocytes, when Abs are not
      protective or are too narrow in viral strain specificity. We have studied
      protective immunity in doubly inactivated (DI) mice devoid of Abs and mature B
      cells. When infected with influenza B virus, these mice cleared the virus in a
      process dependent upon CD8+ T lymphocytes. Cytotoxic activity was detected in
      lung lymphocytes of DI mice after primary or secondary infection, and was
      abrogated by depletion of CD8+ cells in vivo. Challenge experiments showed that
      DI mice could be protected by immunization against reinfection 1 mo later, and
      protection was virus specific. Depletion of CD4+ or CD8+ T cells in vivo during
      the challenge period partially abrogated, and depletion of both subsets
      completely abrogated, the protection. This indicates that both CD4+ and CD8+ T
      cells are required effectors in the optimal control of virus replication. Thus,
      when Abs fail to protect against varying challenge viruses, as is the case with
      variant strains of influenza and HIV, there is hope that T cells might be able to
      act alone.

PMID- 9551988
TI  - Accumulation of the p53 protein allows recognition by human CTL of a wild-type
      p53 epitope presented by breast carcinomas and melanomas.
AB  - The p53 protein is accumulated in tumor cells of many human cancers and can
      elicit in vivo humoral and proliferative responses. Rare reports about p53
      mediated tumor recognition by CTLs have remained questioned. We therefore studied
      a panel of breast tumor and melanoma cell lines that we assayed for the presence
      of accumulated p53 and surface HLA-A2 and for the presentation of p53 epitopes.
      From PBMC of a healthy donor, we have generated a CTL line, D5/L9V, directed
      against HLA-A2-restricted peptide 264-272 from wild-type p53. It efficiently
      lysed breast adenocarcinomas MCF-7, MCF7/RA1, and MDA-MB-231, and melanoma M8,
      which all accumulate the p53 protein. Using competition assays, we made sure that
      tumor lysis by D5/L9V was due to recognition of endogenously produced p53 peptide
      264-272 associated with the HLA-A2.1 molecule on the surface of these tumor
      cells. Cells with undetectable levels of wild-type p53, such as lymphoblastoid
      cells and melanoma M74, were not recognized by D5/L9V. Neither were breast tumor
      cell line MCF7/ADR nor melanoma line M44 because of HLA loss. This study
      therefore shows that it is possible to obtain in vitro CTL lines that
      specifically recognize a p53 epitope spontaneously presented by a variety of HLA
      A2+ transformed cell lines provided they display abnormal patterns of p53
      expression. This work points out that breast tumors and melanomas share a p53
      epitope, and raises hopes for future immunotherapeutic approaches.

PMID- 9551989
TI  - Successful adoptive cellular immunotherapy is dependent on induction of a host
      immune response triggered by cytokine (IFN-gamma and granulocyte/macrophage
      colony-stimulating factor) producing donor tumor-infiltrating lymphocytes.
AB  - Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and systemic low
      dose rIL-2 effectively eradicates pulmonary metastases of the murine MCA-105
      sarcoma. We described earlier that host CD8+ T cells are critical for tumor
      eradication and that successful treatment is associated with production of high
      levels of IFN-gamma and granulocyte/macrophage (GM)-CSF by donor TIL in vitro.
      Here, we propose the mechanism through which adoptively transferred Thy-1.1+ TIL
      induce a host antitumor response in congenic Thy-1.2+ tumor-bearing mice. Donor
      Thy-1.1+ TIL were detected at the tumor site 12 h after transfer. These Thy-1.1+
      cells produced IFN-gamma and GM-CSF in situ. The percentage of Thy-1.1+ TIL at
      the tumor site increased up to 16.4 +/- 4.9% 24 h after transfer but decreased to
      undetectable levels thereafter. In contrast, the percentages of host cells
      producing IFN-gamma and GM-CSF continued to increase at the tumor site. These
      increases were significantly higher in TIL + rIL-2-treated mice compared with
      untreated mice and rIL-2-treated mice 48 h after TIL transfer. The appearance of
      IFN-gamma+ and GM-CSF+ cells was followed by a large influx of host CD4+, CD8+,
      and Thy-1.2+ TIL and eventually by tumor eradication. This response was tumor
      specific since TIL obtained from MCA-205 did not induce high levels of IFN-gamma
      and GM-CSF and did not induce tumor eradication of MCA-105 tumor. Coinjection of
      Thy-1.1+ TIL and anti-IFN-gamma or anti-GM-CSF mAb significantly inhibited
      antitumor efficacy of the TIL + rIL-2 treatment. We conclude that successful
      adoptive immunotherapy in this model is mediated through cytokine production by
      adoptively transferred TIL that induce a host T cell-dependent antitumor
      response.

PMID- 9551990
TI  - Neutrophils but not eosinophils are involved in growth suppression of IL-4
      secreting tumors.
AB  - Local expression of IL-4 by gene-modified tumor cells increases their
      immunogenicity by inducing an inflammatory response that is dominated by
      eosinophils. Eosinophils have been implicated as antitumor effector cells because
      the application of a granulocyte-depleting Ab inhibited rejection of IL-4
      transfected tumors. This Ab did not discriminate between eosinophils and
      neutrophils and, therefore, this experiment could not exclude neutrophils as
      primary effector cells, whereas eosinophils were innocent bystander cells in IL-4
      transfected tumors. We analyzed tumor growth suppression and granulocyte
      infiltration in IL-5-deficient (IL-5(-/-)) mice that had a deficiency of
      eosinophils, using two tumor lines (B16-F10 and MCA205) transfected to secrete IL
      4. IL-4-expressing tumors were at least as efficiently rejected in IL-5(-/-) mice
      as in wild-type mice, despite an almost complete absence of tumor-infiltrating
      eosinophils. However, neutrophils were present in undiminished amounts and their
      depletion partially restored tumor growth. Furthermore, the growth of IL-5
      secreting tumors was not impaired in either wild-type or IL-5(-/-) mice, even
      though it induced eosinophilia in both mouse strains. These findings demonstrate
      that eosinophils can be induced in IL-5(-/-) mice by exogenous IL-5 and argue
      against a compensatory effect of neutrophils in the absence of eosinophils. We
      conclude that 1) infiltration of IL-4 transfected tumors by eosinophils is
      completely IL-5 dependent, 2) eosinophils have no tumoricidal activity, and 3)
      neutrophils are responsible, at least in part, for tumor suppression.

PMID- 9551991
TI  - Helminth antigens selectively differentiate unsensitized CD45RA+ CD4+ human T
      cells in vitro.
AB  - Human filarial helminth infections are characterized by type 2 immune responses
      to parasite Ag that can persist for the life of the individual; one possible
      cause for this may be prenatal exposure to the blood-borne microfilarial (Mf)
      stage of the parasite. To examine the relationship between early exposure to
      filarial Ag and subsequent immune responsiveness, CD45RA+ CD4+ cells frp, normal
      unsensitized donors were stimulated in vitro with soluble microfilarial Ag (MfAg)
      from the filarial parasite Brugia malayi in the presence of APCs. MfAg alone
      induced proliferation and IFN-gamma and IL-5 production in unsensitized CD45RA+
      CD4+ cells, demonstrating the ability of filarial Ags to prime naive T cells in
      the absence of exogenous cytokines and dendritic cells. Adding exogenous
      cytokine(s) (particularly IL-12 and IL-4) during priming was able to alter the
      MfAg-specific responses of CD45RA+ CD4+ cells as well as subsequent responses to
      Ag. Interestingly, priming solely with MfAg led to enhanced IL-5 production
      following Ag restimulation, suggesting that MfAg preferentially primes for type 2
      responses. These data demonstrate that filarial Ags by themselves can
      specifically prime CD45RA+ CD4+ cells in vitro and do so in such a way as to
      deviate the immune response.

PMID- 9551992
TI  - Macrophages kill T9 glioma tumor cells bearing the membrane isoform of macrophage
      colony stimulating factor through a phagocytosis-dependent pathway.
AB  - Rat T9 glioma cells transfected with the gene for the membrane isoform of
      macrophage-CSF (mM-CSF) but not for the secreted isoform of M-CSF were directly
      killed by bone marrow-derived macrophages. Macrophage-mediated cytolysis of the
      mM-CSF-transfected clone was blocked by using chemical inhibitors of phagocytosis
      such as iodoacetate, 2-deoxyglucose, gadolinium chloride, and cytochalasin B. In
      contrast, macrophage-mediated killing of mM-CSF-expressing tumor cells was
      augmented by the microtubule inhibitor, colchicine. Use of nitric oxide and
      reactive oxygen intermediate inhibitors failed to alter the macrophage-mediated
      killing of the mM-CSF-transfected tumor cells. Photomicroscopy, using
      immunohistochemical staining with the anti-Hck Ab to distinguish macrophages from
      tumor cells, revealed that phagocytosis began within 2 h after addition of the mM
      CSF-bearing tumor cells. Photocinematography confirmed that macrophages first
      phagocytosized and then lysed the internalized mM-CSF transfectant cells. Using
      annexin V and acridine orange staining techniques, macrophages phagocytosized
      living mM-CSF-transfected tumor cells.

PMID- 9551993
TI  - Accommodation and T-independent B cell tolerance in rats with long term surviving
      hamster heart xenografts.
AB  - It was previously reported that treatment with leflunomide (LF; 10 mg/kg/day)
      together with cyclosporine (CsA; 10 mg/kg/day) resulted in long term survival of
      hamster heart xenografts (Xg) in rats and that LF could be withdrawn 2 to 4 wk
      after transplantation. To study the mechanisms allowing withdrawal of LF, second
      hamster heart Xgs were transplanted 6 wk after the first xenograft. Only the rats
      that received LF for 4 wk accepted second Xgs (>30 days; n = 5). Hence, after 4
      wk of LF, the rats developed partial B cell tolerance, as they were unable to
      produce T-independent (CsA-resistant) XAbs. Rejection of second Xgs (2-4 days; n
      = 5) in the 2-wk LF group resulted in the formation of IgM xenoantibodies (XAbs)
      localizing together with complement within rejected grafts. However, these XAbs
      did not affect first Xgs, suggesting that the latter Xgs became resistant to this
      IgM XAb-mediated rejection, a phenomenon referred to as accommodation.
      Accommodation was further confirmed as adoptive transfer of IgM XAbs, which
      resulted in hyperacute Xg rejection in naive rats (<1 h; n = 5), did not cause
      rejection in long term survivors (>30 days; n = 4). This was associated with a
      down-regulation of the expression on the graft endothelial cells of adhesion
      molecules (believed to be important expressers of xenogeneic epitopes), such as P
      and E-selectins. Interestingly, these adhesion molecules reappeared after
      retransplanting the accommodated Xgs to naive recipients. In conclusion,
      depending on the duration of the LF treatment, long term survival of hamster
      hearts in CsA-treated rats is based in part on accommodation and in part on T
      independent B cell tolerance.

PMID- 9551994
TI  - Chronic Listeria infection in SCID mice: requirements for the carrier state and
      the dual role of T cells in transferring protection or suppression.
AB  - Listeriosis in mice with the SCID mutation results in a chronic infection. The
      chronic infection is characterized by abundant granulomas and neutrophil
      infiltrates. Both lesions were particularly noticeable in the liver. In the
      liver, about 95% are granulomas with 5% microabscesses involving intrahepatic
      infection. The majority of Listeria resided in membrane-bound vacuolar structures
      of the macrophages and not in the cytosol. Three manipulations resulted in
      alterations in the equilibrium between granulomas and liver microabscesses, with
      massive transfer of the infection to the hepatocyte and dissolution of the
      granulomas: depletion of neutrophils and neutralization of IFN-gamma and TNF
      alpha. We did not find a role for IL-12, IL-10, or nitric oxide. Adoptive
      transfer studies showed a decisive role for both CD4+ and CD8+ T cells for an
      effective immune response, i.e., clearance of bacteria, granuloma formation with
      lymphocytes, and disappearance of microabscess. Clearance of Listeria was induced
      by transfer of CD8+ T cells from mice with targeted disruption of the IFN-gamma
      structural gene (IfgTM1KO), even in the presence of neutralizing mAb to IFN
      gamma. In marked contrast, transfer of CD4+ T cells from IfgTM1KO mice
      exacerbated the infection in the chronically infected SCID mice, resulting in
      increased mortality with dissolution of the granulomas and severe hepatic
      infection with neutrophil infiltration. Thus, these data indicate that both IFN
      gamma-dependent and -independent mechanisms are operative in the context of a
      chronic listerial infection.

PMID- 9551995
TI  - Lymphoid hyperplasia, autoimmunity, and compromised intestinal intraepithelial
      lymphocyte development in colitis-free gnotobiotic IL-2-deficient mice.
AB  - IL-2-deficient (IL-2(-/-)) mice develop disorders of the hemopoietic and immune
      systems characterized by anemia, lymphocytic hyperplasia, and colitis. The
      mechanisms responsible for these abnormalities remain unclear. To investigate the
      underlying basis of autoimmunity, the particular role of commensal gut flora in
      the initiation of colitis, and the role of IL-2 in the development of intestinal
      intraepithelial lymphocytes (iIEL), we evaluated IL-2(-/-) mice reared and
      maintained under gnotobiotic (germfree) conditions. By 8 wk of age, 80% (20 of
      25) of germfree IL-2(-/-) mice show signs of disease, including anemia,
      disturbances in bone marrow hemopoietic cells, lymphocytic hyperplasia, and
      generalized autoimmunity, similar to those seen in specific pathogen-free (SPF)
      IL-2(-/-) mice. In striking contrast to SPF IL-2(-/-) mice, germfree IL-2(-/-)
      mice do not develop colitis. However, the numbers of gammadelta+ and TCR
      alphabeta+ CD8 alphaalpha+ iIELs are reduced, and in lethally irradiated SPF IL
      2(+/+) mice, reconstituted with IL-2(-/-) bone marrow TCR gammadelta+ iIELs fail
      to develop, consistent with an important role of IL-2/IL-2R signaling in the
      development of gammadelta iIELs. Consequently, our findings demonstrate that the
      colitis seen in SPF IL-2(-/-) mice depends upon the presence of intestinal
      bacterial flora and that environmental Ags are not responsible for the anemia and
      extraintestinal lymphoid hyperplasia that occur in IL-2(-/-) mice. Thus, germfree
      IL-2(-/-) mice represent a unique system in which the role of IL-2 deficiency in
      hemopoietic and immune system disorders can be investigated in dissociation from
      complications that may arise due to colitis.

PMID- 9551996
TI  - Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily
      member.
AB  - Human CD38 is a cell surface molecule involved in the regulation of lymphocyte
      adhesion to endothelial cells. This suggests that HUVEC bear a ligand(s) for CD38
      on the cell surface. By means of the mAb Moon-1, which specifically inhibits CD38
      mediated cell adhesion, we have identified a trans-membrane 130-kDa molecule
      acting as a ligand for CD38. Here, we report that the molecule recognized by the
      Moon-1 mAb is CD31, a member of the Ig superfamily. This conclusion is based on
      1) cross-inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2)
      sequential immunoprecipitation experiments using Moon-1 and known anti-CD31 mAbs,
      and 3) reactivity of the Moon-1 mAb with CD31 transfectants. Further, CD31 and
      CD38 cognate interactions were found to modulate heterotypic adhesion as well as
      to implement cytoplasmic calcium fluxes identical to those obtained by means of
      agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages
      for a panel of cytokines, markedly increased upon receptor-ligand interactions.
      These results suggest that the interplay between CD38 and its ligand CD31 is an
      important step in the regulation of cell life and of the migration of leukocytes
      (and CD38+ cancer cells) through the endothelial cell wall.

PMID- 9551997
TI  - IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in
      experimental periodontitis.
AB  - Periodontal disease is the most frequent cause of tooth loss in humans and is the
      most prevalent disease associated with bone loss, including osteoporosis.
      Periodontal destruction is initiated by bacteria that colonize the tooth surface,
      leading to inflammation and bone resorption. To assess the roles of IL-1 and TNF
      in this process, studies were conducted in a Macaca fascicularis primate model of
      experimental periodontitis. Function-blocking soluble receptors to IL-1 and TNF
      were applied by local injection to sites with induced periodontal destruction and
      compared with similar sites injected with vehicle alone. The results indicate
      that injection of soluble receptors to IL-1 and TNF inhibited by approximately
      80% the recruitment of inflammatory cells in close proximity to bone. The
      formation of osteoclasts was reduced by 67% at the experimental sites compared
      with that at the control sites, and the amount of bone loss was reduced by 60%.
      All results were statistically significant (p < 0.01). These findings indicate
      that a significant component of the pathologic process of periodontitis is due to
      IL-1/TNF activity, since inhibiting IL-1/TNF reduces both inflammatory cell
      recruitment and bone loss. The data also suggest that inflammation associated
      with gingivitis is actively protective, since blocking further up-regulation of
      the host response with IL-1/TNF inhibitors does not cause periodontal damage.
      Furthermore, these results coupled with recent evidence that IL-1 and TNF
      participate in endocrine-associated osteoporosis suggest that multiple
      pathologies involving excessive loss of bone may operate through a common
      mechanism involving IL-1 and/or TNF.

PMID- 9551998
TI  - Inhibition of proinflammatory molecule production by adenovirus-mediated
      expression of a nuclear factor kappaB super-repressor in human intestinal
      epithelial cells.
AB  - NF-kappaB plays a major role in the transcriptional regulation of many
      proinflammatory genes in multiple cell lineages, including intestinal epithelial
      cells (IEC). Activation of NF-kappaB requires both phosphorylation and
      degradation of its natural cytoplasmic inhibitor, IkappaB. We tested whether a
      super-repressor of NF-kappaB activity, which is a mutated nondegradable IkappaB
      alpha resistant to phosphorylation and degradation, could be delivered into IEC
      using an adenoviral vector (Ad5 IkappaB) and determined the antiinflammatory
      potential of this inhibitor following different stimuli. We showed for the first
      time that recombinant adenovirus efficiently infected (>80%) transformed as well
      as primary IEC. Cytoplasmic levels of the NF-kappaB super-repressor protein were
      more than 50-fold higher than those of endogenous IkappaB, and this mutated
      IkappaB was resistant to IL-1beta-induced degradation. Immunofluorescent RelA
      nuclear staining was strongly inhibited in Ad5 IkappaB-infected IEC compared with
      control Ad5LacZ and NF-kappaB, but not AP-1 binding activity, was reduced by more
      than 70% as measured by electrophoretic mobility shift assay (EMSA). Induction of
      inducible nitric-oxide synthase (iNOS), IL-1beta, and IL-8 genes by IL-1beta, TNF
      alpha, or PMA was blocked in Ad5 IkappaB-infected cells but not in Ad5 LacZ
      controls as assayed by RT-PCR and ELISA. In addition, IL-1beta-induced IL-8
      secretion was totally inhibited by Ad5 IkappaB in primary colonic IEC. We
      conclude that an adenoviral vector efficiently transfers a nondegradable IkappaB
      in both transformed and native IEC. The strong inhibition of NF-kappaB activity
      and the resulting down-regulation of multiple proinflammatory molecules by Ad5
      IkappaB suggests an exciting approach for in vivo intestinal gene therapy and
      illustrates the key role of NF-kappaB in transcriptional regulation of the
      inflammatory phenotype of IEC.

PMID- 9551999
TI  - Regulated production of type I collagen and inflammatory cytokines by peripheral
      blood fibrocytes.
AB  - We recently described a novel population of blood-borne cells, termed fibrocytes,
      that display a distinct cell surface phenotype (collagen+/CD13+/CD34+/CD45+),
      rapidly enter sites of tissue injury, and contribute to scar formation. To
      further characterize the role of these cells in vivo, we examined the expression
      of type I collagen and cytokine mRNAs by cells isolated from wound chambers
      implanted into mice. Five days after chamber implantation, CD34+ fibrocytes but
      not CD14+ monocytes or CD90+ T cells expressed mRNA for type I collagen.
      Fibrocytes purified from wound chambers also were found to express mRNA for IL
      1beta, IL-10, TNF-alpha, JE/MCP, MIP-1alpha, MIP-1beta, MIP-2, PDGF-A, TGF-beta1,
      and M-CSF. The addition of IL-1beta (1-100 ng/ml), a critical mediator in wound
      healing, to fibrocytes isolated from human peripheral blood induced the secretion
      of chemokines (MIP-1alpha, MIP-1beta, MCP-1, IL-8, and GRO alpha), hemopoietic
      growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF
      alpha. By contrast, IL-1beta decreased the constitutive secretion of type I
      collagen as measured by ELISA. Additional evidence for a role for fibrocytes in
      collagen production in vivo was obtained in studies of livers obtained from
      Schistosoma japonicum-infected mice. Mouse fibrocytes localized to areas of
      granuloma formation and connective matrix deposition. We conclude that fibrocytes
      are an important source of cytokines and type I collagen during both the
      inflammatory and the repair phase of the wound healing response. Furthermore, IL
      1beta may act on fibrocytes to effect a phenotypic transition between a
      repair/remodeling and a proinflammatory mode.

PMID- 9552000
TI  - RANTES-induced T cell activation correlates with CD3 expression.
AB  - The chemokine RANTES induces a unique biphasic cytoplasmic Ca2+ signal in T
      cells. The first phase of this signal, similar to that of other chemokines, is G
      protein mediated and chemotaxis associated. The second phase of this signal,
      unique to RANTES and evident at concentrations greater than 100 nM, is tyrosine
      kinase linked and results in a spectrum of responses similar to those seen with
      antigenic stimulation of T cells. We show here that certain jurkat T cells
      responded to RANTES solely through this latter pathway. A direct correlation
      between the RANTES-induced second phase response and CD3 expression was
      demonstrated in these cells. Sorting the Jurkat cells into CD3(high) and CD3(low)
      populations revealed that only the CD3(high) cells were responsive to RANTES.
      Furthermore, stimulation of these Jurkat cells with anti-CD3 mAb significantly
      depresses their subsequent response to RANTES. While a RANTES-specific chemokine
      receptor is expressed at a low level on these Jurkat cells, the RANTES-induced
      activation is dependent on the presence of the TCR. Thus, stimulation through TCR
      may partially account for RANTES' unique pattern of signaling in T cells.

PMID- 9552002
TI  - CD8+ myelin peptide-specific T cells can chemoattract CD4+ myelin peptide
      specific T cells: importance of IFN-inducible protein 10.
AB  - The demyelination process that occurs in the central nervous system (CNS) of
      patients with multiple sclerosis (MS) is due, in part, to an inflammatory
      response in which CD4+ and CD8+ T cells and macrophages infiltrate white matter.
      While it is thought that the inflammatory and demyelination process in MS is the
      product of Th1-associated cytokines secreted by CD4+ myelin protein-specific T
      cells present in the CNS, the mechanisms that are responsible for the recruitment
      and maintenance of these myelin-reactive CD4+ T cells in the CNS have not been
      elucidated. We have shown previously that CD8+ CTL that recognize peptides
      derived from sequences of the myelin proteolipid protein (PLP) presented by HLA
      class I molecules can be generated in vitro, and that these PLP-specific CD8+ CTL
      secrete the proinflammatory chemokines macrophage-inflammatory protein-1alpha and
      -1beta, IL-16, and IP-10. In this study, we demonstrate that soluble products of
      these PLP-specific CD8+ CTL can chemoattract CD4+ T cells that are specific for a
      myelin basic protein peptide and a PLP peptide, and that the majority of this
      chemotactic activity is mediated by IFN-inducible protein 10. These results
      demonstrate that PLP-specific CD8+ T cells can play a role in the recruitment and
      retention of myelin-derived peptide-specific CD4+ T cells, and indicate that they
      may play a proinflammatory role in the pathogenesis of MS.

PMID- 9552001
TI  - Importance of MEK in neutrophil microbicidal responsiveness.
AB  - Exposure of neutrophils to inflammatory stimuli such as the chemoattractant FMLP
      leads to activation of responses including cell motility, the oxidative burst,
      and secretion of proteolytic enzymes. A signaling cascade involving sequential
      activation of Raf-1, mitogen-activated protein kinase (MEK), and extracellular
      signal regulated kinase (ERK) is also rapidly activated after agonist exposure.
      The temporal relationship between these events suggests that the kinases may be
      involved in triggering the effector functions, but direct evidence of a causal
      relationship is lacking. To assess the role of the MEK/ERK pathway in the
      activation of neutrophil responses, we studied the effects of PD098059, a potent
      and selective inhibitor of MEK. Preincubation of human neutrophils with 50 microM
      PD098059 almost completely (>90%) inhibited the FMLP-induced activation of MEK-1
      and MEK-2, the isoforms expressed by neutrophils. This dose of PD098059 virtually
      abrogated chemoattractant-induced tyrosine phosphorylation and activation of ERK
      1 and ERK-2, implying that MEKs are the predominant upstream activators of these
      mitogen-activated protein kinases. Pretreatment of neutrophils with the MEK
      antagonist inhibited the oxidative burst substantially and phagocytosis only
      moderately. In addition, PD098059 antagonized the delay of apoptosis induced by
      exposure to granulocyte-macrophage CSF. However, the effects of PD098059 were
      selective, as it failed to inhibit other responses, including chemoattractant
      induced exocytosis of primary and secondary granules, polymerization of F-actin,
      chemotaxis, or activation of phospholipase A2. We conclude that MEK and ERK
      contribute to the activation of the oxidative burst and phagocytosis, and
      participate in cytokine regulation of apoptosis.

PMID- 9552003
TI  - Regulation of chemokine gene expression in human peripheral blood neutrophils
      phagocytosing microbial pathogens.
AB  - Production of chemokines (chemotactic cytokines) by neutrophils is likely to be
      important in the regulation of inflammation and the control of infection. In this
      study we show that exposure of human neutrophils to various microbial pathogens
      leads to the production of both macrophage inflammatory protein 1alpha (MIP
      1alpha) and IL-8. The bacterial microbes, Salmonella typhimurium and Pseudomonas
      aeruginosa, and Staphylococcus aureus all strongly induced both IL-8 and MIP
      1alpha secretion, whereas Streptococcus pneumoniae, Staphylococcus epidermidis,
      and the opportunistic yeast Candida albicans were less potent. Saccharomyces
      cerevisiae and zymosan both induced IL-8 secretion but failed to stimulate that
      of MIP-1alpha. Coincubation of neutrophils with the proinflammatory cytokine TNF
      alpha and the micro-organisms also led to differential expression of MIP-1alpha
      and IL-8. Significant enhancement of the induction of both MIP-1alpha and IL-8 by
      S. typhimurium, P. aeruginosa, and S. pneumoniae as well as by C. albicans was
      observed. In contrast, while IL-8 production in response to S. cerevisiae and
      zymosan was enhanced in the presence of TNF-alpha, no MIP-1alpha was produced.
      These combined results indicate that while neutrophils exposed to some micro
      organisms alone or in the presence of inflammatory cytokines such as TNF-alpha
      will produce both MIP-1alpha and IL-8, resulting in generation of signals for the
      recruitment of mononuclear leukocytes and neutrophils, respectively, certain
      types of microorganisms can skew this response toward synthesis of IL-8.

PMID- 9552004
TI  - Apical secretion of a pathogen-elicited epithelial chemoattractant activity in
      response to surface colonization of intestinal epithelia by Salmonella
      typhimurium.
AB  - Modeling Salmonella-epithelial cell interaction in vitro has led to the
      realization that epithelial cells are crucial in orchestrating neutrophil (PMN)
      responses, in part by stimulating basolateral release of epithelial chemokines,
      including IL-8. However, such basolaterally released chemokines, while likely
      important in orchestration of PMN movement across the subepithelial matrix, are
      unlikely to be responsible for the final step of transepithelial migration of PMN
      and entry into the apical compartment. We now show that S. typhimurium attachment
      to T84 cell apical epithelial membranes induces polarized apical secretion of a
      pathogen-elicited epithelial chemoattractant (PEEC) bioactivity. Experiments
      employing semipurified PEEC indicate that it is released in a polarized apical
      fashion and is sufficient to explain the observed final step of transepithelial
      migration of PMN induced by Salmonella-apical membrane interaction. By
      preliminary physical characterization and profiles of PMN activation, PEEC
      appears to be a novel PMN chemotactic bioactivity. This 1- to 3-kDa nominal
      molecular mass chemokine-like bioactivity directly stimulates PMN via a pertussis
      toxin-sensitive receptor and elicits a Ca2+ signal. While these latter features
      are shared by most other chemokines, analysis of PEEC-elicited PMN activation
      reveals that, unlike these other agonists, PEEC, even at saturating
      concentrations, elicits chemotactic activity in the absence of stimulation of
      superoxide production and/or release of primary and/or secondary granules. These
      data suggest that the apically released PEEC activity appears to represent a
      novel epithelial-derived chemoattractant that directs PMN movement across
      epithelial monolayers.

PMID- 9552005
TI  - Adhesion molecule mechanisms mediating monocyte migration through synovial
      fibroblast and endothelium barriers: role for CD11/CD18, very late antigen-4
      (CD49d/CD29), very late antigen-5 (CD49e/CD29), and vascular cell adhesion
      molecule-1 (CD106).
AB  - Monocytes migrate through vascular endothelium, and then in connective tissue. As
      a model of this process, we investigated adhesion molecules involved in monocyte
      migration through HUVEC and a barrier of human synovial fibroblasts (HSF).
      Minimal spontaneous monocyte migration (6-7%) occurred through either cell
      barrier, but this increased markedly (27-35% of added monocytes) when a C5a
      chemotactic gradient was present. Migration across unstimulated HUVEC was
      partially inhibited (40%) by mAb to CD18 (beta2 integrin) and completely blocked
      by anti-CD18 plus anti-alpha4 (CD49d; very late Ag-4 (VLA-4)) mAbs. In contrast,
      migration across HSF induced by C5a or monocyte chemoattractant protein-1 was not
      inhibited by mAb to CD18 and was only partially inhibited (33%) in combination
      with anti-alpha4 mAb. The CD18- and VLA-4-independent migration across HSF was
      completely inhibited by mAb to alpha5 of VLA-5. The inhibitory effect of mAbs to
      VLA-4 and VLA-5 was on the monocyte and required blockade of CD11/CD18 to be
      observed. In contrast to HSF, no role for VLA-5 in monocyte transendothelial
      migration was detected. Both HSF and IL-1-stimulated HUVEC expressed vascular
      cell adhesion molecule-1 (VCAM-1). However, VLA-4-mediated monocyte migration
      across HSF was only partially dependent on VCAM-1, in contrast to
      transendothelial migration, which was completely blocked by anti-VCAM-1 mAbs. In
      conclusion, unlike transendothelial migration, for which VLA-4 is the alternative
      mechanism to CD11/CD18 on monocytes, both VLA-4 and VLA-5 can mediate monocyte
      migration through fibroblast barriers. In addition to VCAM-1, other ligand(s) on
      HSF are also involved in the VLA-4-mediated migration.

PMID- 9552006
TI  - Effect of C1 inhibitor on inflammatory and physiologic response patterns in
      primates suffering from lethal septic shock.
AB  - We evaluated the effect of C1 inhibitor (C1-inh), an inhibitor of the classical
      pathway of complement and the contact system, on the physiologic and inflammatory
      response in baboons suffering from lethal Escherichia coli sepsis. Five animals
      pretreated with 500 U/kg C1-inh (treatment group; n = 5), followed by a 9-h
      continuous infusion of 200 U/kg C1-inh subsequent to bacterial challenge, were
      compared with five controls receiving E. coli alone. Of the treatment group, one
      animal survived and another lived beyond 48 h, whereas all control animals died
      within 27 h. In four of five treated animals, less severe pathology was observed
      in various target organs. C1-inh administration did not prevent the hemodynamic
      or hematologic changes observed upon E. coli infusion. The activation of
      fibrinolysis and the development of disseminated intravascular coagulation were
      essentially unaffected by C1-inh. However, C1-inh supplementation significantly
      reduced decreases in plasma levels of factor XII and prekallikrein and abrogated
      the systemic appearance of C4b/c, indicating substantial inhibition of activation
      of the contact system and the classical complement pathway, respectively.
      Furthermore, treated animals displayed a reduced elaboration of various cytokines
      including TNF, IL-10, IL-6, and IL-8. Thus, the administration of C1-inh may have
      a beneficial but modest effect on the clinical course and outcome of severe
      sepsis in nonhuman primates. We suggest that activated complement and/or contact
      system proteases may, at least in part, contribute to the attendant
      manifestations of septic shock through an augmentation of the cytokine response.

PMID- 9552007
TI  - Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin
      alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1
      signaling.
AB  - Lymphotoxin (LT, LT alpha, TNF beta) is a member of the immediate TNF family that
      also includes TNF-alpha and lymphotoxin-beta (LT beta). LT is produced by
      activated lymphocytes and functions as either a secreted homotrimer or a membrane
      associated heterotrimer that includes the transmembrane protein LT beta. Secreted
      LT alpha3 can bind to two cell surface receptors, TNFR1 and TNFR2, while the
      membrane-bound heterotrimer LT alpha1beta2 has been shown to interact with a
      distinct receptor, LT betaR. LT alpha induces inflammation at the sites of
      expression of a rat insulin promoter-driven lymphotoxin (RIPLT) transgene in the
      pancreas and kidney. To determine the role of the various ligands and their
      receptors in LT-induced inflammation, mice deficient in either TNFR1, TNFR2, or
      LT beta were crossed to RIPLT-transgenic mice. Our results indicate that LT alpha
      induced inflammation is dependent on the interaction of LT alpha3 with TNFR1, and
      there is no obvious role for TNFR2, since in its absence, LT alpha-induced
      inflammation is quantitatively and qualitatively similar to that seen in the wild
      type. However, the absence of LT beta results in accentuated infiltration of the
      kidney with an increase in the proportion of memory cells in the infiltrate.
      These data show a crucial role for the secreted LT alpha3 signaling via TNFR1 in
      LT alpha-induced inflammation, and a separate and distinct role for the membrane
      LT alpha1beta2 form in this inflammatory process.

PMID- 9552008
TI  - Distinct classes of chaperoned IL-6 in human blood: differential immunological
      and biological availability.
AB  - Transport of IL-6 in blood is fundamental to the biology of this cytokine. In the
      present study, IL-6 transport, immunological reactivity, and biological
      availability were investigated in blood from melanoma patients subjected to
      different active specific immunization regimens (an anti-idiotypic mAb
      immunization protocol (mAb-keyhole limpet hemocyanin (KLH)-Calmette-Guerin
      bacillus (BCG), an autologous anti-cancer vaccine protocol (AAAP), or both). Sera
      were subjected to Sephadex G-200 gel filtration chromatography, and the structure
      and biological activity of IL-6 complexes in the eluate fractions were probed
      using five IL-6 ELISAs and two bioassays. Sera from patients administered mAb
      KLH+BCG followed by AAAP contained three distinct classes of IL-6 eluting at 30,
      200, and 450 kDa, each with its characteristic ELISA reactivity and bioactivity:
      the 30- and 450-kDa complexes were bioactive in the B9 and Hep3B assays, but the
      200-kDa complex was not. The 30- and 450-kDa IL-6 complexes were preferentially
      reactive in the 7IL6/5IL6 ELISA, the 200-kDa IL-6 complexes were preferentially
      reactive in the 4IL6/5IL6 ELISA, while the three commercial ELISAs (R&D, Endogen,
      and Genzyme) detected essentially only the 30-kDa IL-6. In contrast, 1) sera from
      AAAP patients contained biologically active 30- and 450-kDa IL-6 complexes, while
      2) sera from mAb-KLH+BCG patients contained 200-kDa IL-6 complexes inactive in ex
      vivo bioassays. Both the 450- and 200-kDa complexes included soluble IL-6R, with
      the 200-kDa complexes additionally containing ligand-occupied anti-IL-6 and anti
      soluble IL-6R IgG. The data indicate the existence of specific mechanisms that
      regulate the transport and function of IL-6 in vivo.

PMID- 9552010
TI  - CDR3 size spectratyping and sequencing of spectratype-derived TCR of spinal cord
      T cells in autoimmune encephalomyelitis.
AB  - To characterize the nature of autoimmune disease-inducing T cells in the target
      organ, oligoclonal expansion of spinal cord T cells of Lewis rats with
      experimental autoimmune encephalomyelitis (EAE) was examined by complementarity
      determining region 3 (CDR3) size spectratyping. It is known that TCR of in vitro
      established myelin basic protein-specific T cell clones and lines have a short
      CDR3 and that the amino acid sequence in this region is highly preserved. On the
      basis of these findings, we analyzed 22 spectratypes of the TCR beta-chain
      (Vbeta1-20). Among them, only Vbeta8.2 and Vbeta17 showed oligoclonal expansion
      of TCR with a short CDR3 at the early stage of EAE. More interestingly, the
      spectratype profile of Vbeta8.2 seen at the early stage was preserved throughout
      the course of EAE, whereas that of Vbeta17 became more diverse at the peak stage
      of the disease. Analysis of nucleotide and predicted amino acid sequences of
      Vbeta8.2 CDR3 derived from the spectratypes revealed that the clones with
      CASSDSSYEQYFGPG, which is one of the representative sequences of encephalitogenic
      T cell clones, constituted the predominant population not only at the early stage
      but also at the peak and recovery stages (71, 71, and 60%, respectively). These
      findings imply that although the phenotype of T cells in the target organ
      diversifies as the autoimmune disease progresses, disease-associated TCR
      spectratype(s) are preserved throughout the course of the disease. Thus, CDR3
      size spectratyping is a powerful tool for the screening of disease-inducing T
      cells in an autoimmune disease of unknown pathomechanism.

PMID- 9552009
TI  - A model of peptide-induced lupus autoimmune B cell epitope spreading is strain
      specific and is not H-2 restricted in mice.
AB  - Anti-Sm is a common and specific autoantibody found in systemic lupus
      erythematosus. The peptide PPPGMRPP from Sm B/B' is an early target of the
      autoimmune response in some anti-Sm-positive human patients. After immunization
      with this peptide on a MAP backbone, rabbits develop anti-Sm autoantibodies with
      B cell epitope spreading of the autoimmune response as well as other features of
      lupus autoimmunity. Various strains of inbred mice have been immunized with
      peptide PPPGMRPP or PSQQVMTP (nonantigenic region of Sm B/B') in Freund's
      adjuvant or with no peptide. All peptide-immunized mouse strains eventually
      develop high titers of specific anti-peptide of immunization Abs. Mice immunized
      with Freund's adjuvant alone have no measurable Ab binding to the PPPGMRPP
      peptide. With time, nearly half the mouse strains tested develop Abs that react
      with additional regions of Sm B/B' and Sm D. All the regions bound by mouse serum
      are major epitopes of the human systemic lupus erythematosus anti-Sm response.
      These same strains also develop significant anti-Sm and anti-nuclear
      ribonucleoprotein titers. In addition, some of these strains demonstrate positive
      anti-nuclear Abs and anti-dsDNA Abs. Experiments with congenic H-2 mice
      demonstrate that the H-2 region does not play a role in spreading the immune
      response from the peptide of immunization to other epitopes of the spliceosome.
      These results present a new murine model of B cell epitope spreading and lupus
      autoimmunity induced by peptide immunization that is strain specific and not
      apparently dependent upon the loci at H-2.

PMID- 9552011
TI  - Introduction: mechanisms and management of COPD: we can do better--it's time for
      a re-evaluation.

PMID- 9552012
TI  - COPD: overview of definitions, epidemiology, and factors influencing its
      development.
AB  - COPD is a heterogeneous collection of conditions that can affect various
      structures within the lung in a number of different ways. These various processes
      can all result in limitation of expiratory airflow. If severe enough, this
      physiologic abnormality defines COPD. The various conditions that can lead to
      this syndrome are prevalent and often relentlessly progressive. In aggregate,
      they represent an important public health problem. This supplement outlines
      diagnostic and therapeutic strategies by which the practitioner can assist
      patients suffering from this condition.

PMID- 9552013
TI  - The role of infection in COPD.
AB  - Clinical studies of acute exacerbations of COPD are difficult because of the
      heterogeneous nature of COPD, diffuse symptoms that can vary spontaneously, and
      difficulties in defining clinical response both in the short and long term. The
      role of bacterial infection, and thus use of antibiotics, in COPD is
      controversial. The available evidence shows that bacterial infection has a
      significant role in acute exacerbations, but its role in disease progression is
      less certain. Upper respiratory tract commensals, such as nontypable Haemophilus
      influenzae, cause most bronchial infections by exploiting deficiencies in the
      host defenses. Some COPD patients are chronically colonized by bacteria between
      exacerbations, which represents an equilibrium in which the numbers of bacteria
      are contained by the host defenses but not eliminated. When an exacerbation
      occurs, this equilibrium is upset and bacterial numbers increase, which incites
      an inflammatory response. Neutrophil products can further impair the mucosal
      defenses, favoring the bacteria, but if the infection is overcome, symptoms
      resolve. However, if the infection persists, chronic inflammation may cause lung
      damage. About half of exacerbations involve bacterial infection, but these
      patients are not easy to differentiate from those who are uninfected, which means
      that antibiotics have to be given more often than is strictly necessary. Further
      research is needed to characterize those patients in whom bacterial infection has
      a more important role.

PMID- 9552014
TI  - The value of antibiotics and the outcomes of antibiotic therapy in exacerbations
      of COPD.
AB  - COPD is the fifth leading cause of death in the United States, and acute
      respiratory infections account for a significant proportion of all primary care
      visits. Approximately one half of all exacerbations of COPD can be attributed to
      bacterial infection, and antibiotic therapy has been demonstrated to improve
      clinical outcomes and hasten clinical and physiologic recovery. The major
      pathogen continues to be Haemophilus influenzae, and resistance to beta-lactam
      antibiotics such as ampicillin can be expected in 20 to 40% of isolated strains.
      Certain high-risk patients, in whom the cost of clinical treatment failure is
      high, can be identified by simple clinical criteria. Patients with significant
      cardiopulmonary comorbidity, frequent purulent exacerbations of COPD, advanced
      age, generalized debility, malnutrition, chronic corticosteroid administration,
      long duration of COPD, and severe underlying lung function tend to fail therapy
      with older drugs, such as ampicillin, and early relapse can be expected.
      Treatment directed toward resistant pathogens with potent bactericidal drugs may
      be expected to lead to improved clinical outcomes and overall lower costs,
      particularly if hospital admissions and respiratory failure can be prevented.
      Future studies examining the role of antibiotics should enroll these high-risk
      patients to determine if new therapies have significant clinical, quality-of
      life, and economic advantages over older agents.

PMID- 9552015
TI  - Supportive therapy in COPD.
AB  - Supportive therapy in COPD includes long-term oxygen therapy (LTOT) and patient
      support groups as two cornerstones in a comprehensive program of care known as
      pulmonary rehabilitation. The rich history of LTOT dating to the early 1960s and
      bolstered by excellent controlled clinical trials of the 1970s, along with
      additional advances, provided an effective therapy which improved both the
      quality and length of life in patients with COPD. Many patients with oxygen gain
      insight into coping with advanced COPD through patient support groups. The need
      for more cosmetically pleasing oxygen delivery systems to the nose, and future
      directions in providing oxygen in the home, remain challenges.

PMID- 9552016
TI  - Pulmonary rehabilitation.
AB  - There has been a resurgence of interest in pulmonary rehabilitation mainly
      because the prevalence of COPD has increased, scientific studies document
      consistent benefits (increased exercise endurance and reduced dyspnea), and
      thoracic surgeons recognize that preoperative and postoperative conditioning
      enhances the results of lung volume reduction surgery and lung transplantation.
      Although education and psychosocial/behavioral interventions are important
      components of a multidimensional program, exercise training of the upper and
      lower extremities is essential to achieve the described improvements. Current
      programs vary considerably in the frequency, intensity, and duration of exercise
      reconditioning. Two "key" questions relating to pulmonary rehabilitation are as
      follows. What is an appropriate training intensity? How should patients monitor
      the training intensity? Maintenance exercise programs and the development of home
      or community-based programs will be important future developments.

PMID- 9552017
TI  - Lung Transplantation for COPD.
AB  - In appropriately selected patients with COPD and alpha1-antitrypsin deficiency
      emphysema, lung transplantation prolongs life, improves functional capacity, and
      enhances quality of life. However, rejection remains an obstacle to better medium
      term results, and lung transplantation is a treatment, not a cure and not a
      panacea.

PMID- 9552018
TI  - Lung volume reduction surgery: answering the crucial questions.
AB  - Emphysema and other forms of COPD are not only common, but also have a poor
      prognosis. Mortality with severe COPD may be as high as 60% at 5 years and is
      associated with a significant degree of disability and cost to the health-care
      system. Building on Dr. Otto Brantigan's experience in the 1950s, when multiple
      wedge resections of emphysematous lung were performed to decrease lung volume,
      thereby improving airflow and reducing hyperinflation, recent investigators,
      utilizing improved surgical and anesthetic technique, have redeveloped a surgical
      approach to the treatment of emphysema. The operations used to treat emphysema
      include excision of large bullae (bullectomy) and resection of diffusely
      emphysematous lung and are variously known as lung volume reduction surgery
      (LVRS), pneumectomy, and reduction pneumoplasty. These operations aim for a 20 to
      30% reduction in lung volume and may be performed by stapler or laser resection,
      or both. The mechanisms of benefit have been attributed to enhanced elastic
      recoil, correction of ventilation perfusion mismatch, improved efficiency of
      respiratory musculature, and improved right ventricular filling. Questions that
      remain to be answered include duration of benefits, safety, and cost of LVRS. The
      National Heart, Lung, and Blood Institute and the Health Care Financing
      Administration have responded to the demand for more access to and information
      about LVRS by organizing both a national registry and controlled clinical trial
      of these procedures over a 7-year period. This multicenter trial intends to
      enroll patients with end-stage emphysema to compare methods of bilateral LVRS to
      maximal medical therapy.

PMID- 9552019
TI  - Standards for the optimal management of COPD: a summary.
AB  - Tobacco smoking is the main cause of COPD, and encouragement and support in
      smoking cessation is the best way to help the patient with COPD. The three major
      goals of COPD management are to lessen airflow limitation, to prevent and treat
      secondary medical complications, and to decrease respiratory symptoms and improve
      quality of life. Outpatient pharmacotherapy should be organized in a stepwise
      manner according the severity of disease, the aims being to induce
      bronchodilation, reduce inflammation, and facilitate expectoration, although the
      role of anti-inflammatory and mucolytic treatment of COPD has not been clearly
      established. Patients whose conditions are not well controlled with optimal
      pharmacotherapy are candidates for enrollment in a pulmonary rehabilitation
      program. Correction or prevention of hypoxemia is a priority, and long-term
      oxygen therapy supplementation prolongs survival in hypoxemic patients. With only
      limited data on criteria for hospital admission and the objectives of
      hospitalization, the published standards on the management of COPD include an
      expert consensus statement on these aspects of hospital care. Surgery, special
      considerations such as sleep, nutrition, and air travel, and ethical issues are
      discussed.

PMID- 9552020
TI  - Ewing's sarcoma oncogene structure: a novel prognostic marker?

PMID- 9552021
TI  - Germ cell tumors: there is still plenty to learn.

PMID- 9552022
TI  - EWS-FLI1 fusion transcript structure is an independent determinant of prognosis
      in Ewing's sarcoma.
AB  - PURPOSE: More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and
      FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level,
      the EWS-FLI1 rearrangements show great diversity. Specifically, many different
      combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and
      result in differences in the length and composition of the chimeric protein,
      which functions as an oncogenic aberrant transcription factor. In the most common
      fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the
      fundamental pathogenetic lesion in ES, the molecular heterogeneity of these
      fusion transcripts may have functional and clinical significance. PATIENTS AND
      METHODS: We performed a clinical and pathologic analysis of 112 patients with ES
      in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase
      polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were
      available in 99 patients treated with curative intent. Median follow-up in these
      99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate
      survival analyses were performed that included other prognostic factors, such as
      age, tumor location, size, and stage. RESULTS: Among the 99 patients suitable for
      survival analysis, the tumors in 64 patients contained the type 1 fusion and in
      35 patients contained less common fusion types. Stage at presentation was
      localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] =
      2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were,
      respectively, independent negative and positive prognostic factors for overall
      survival by multivariate analysis. Among 74 patients with localized tumors, the
      type 1 EWS-FLI1 fusion was also a significant positive predictor of overall
      survival (RR = 0.32; P = .034) by multivariate analysis. CONCLUSION: EWS-FLI1
      fusion type appears to be prognostically relevant in ES, independent of tumor
      site, stage, and size. Further studies are needed to clarify the biologic basis
      of this phenomenon.

PMID- 9552023
TI  - Successful treatment of stage III neuroblastoma based on prospective biologic
      staging: a Children's Cancer Group study.
AB  - PURPOSE: To identify a biologically favorable and unfavorable subset of patients
      with Evans stage III neuroblastoma and to determine whether treatment
      stratification would improve the event-free survival (EFS) for high-risk patients
      and maintain excellent EFS for the lower-risk patients. PATIENTS AND METHODS:
      Risk stratification was performed by age, MYCN gene copy number, Shimada
      histopathologic classification, and serum ferritin level. Lower-risk patients
      were treated on the less intensive Children's Cancer Group (CCG)-3881, whereas
      high-risk patients were treated on CCG-3891, which included more intensive
      multimodality therapy and, in some cases, autologous bone marrow transplantation
      (ABMT). RESULTS: Of 228 Evans stage III patients entered onto the study, 92% also
      met the definition of International Neuroblastoma Staging System (INSS) stage 3.
      One hundred forty-three patients met the lower-risk criteria, which included 89
      patients less than 1 year of age and 54 patients 1 year of age or greater, and
      favorable biology, whereas 85 patients were 1 year of age or greater and
      biologically unfavorable. Biologically unfavorable patients 1 year of age or
      greater who underwent gross surgical resection had improved survival, whereas the
      outcome of infants or biologically favorable older patients did not change
      according to resection. The EFS rate at 4 years was 100% for the patients with
      favorable biology of any age, 90% for those less than 1 year of age but with at
      least one unfavorable characteristic, and 54% for Evans stage III patients 1 year
      of age or greater with unfavorable biology. Age, ferritin level, MYCN copy
      number, Shimada histopathology, primary site, and intraspinal extension were
      significant univariate prognostic factors for all patients, but only MYCN copy
      number and age were independent factors in multivariate analyses. CONCLUSION: The
      excellent survival of the biologically favorable group and the historically
      improved EFS of the biologically unfavorable group suggest that biologic staging
      should be used to define the prognosis and treatment of stage III neuroblastoma.

PMID- 9552024
TI  - Spontaneous regression of localized neuroblastoma detected by mass screening.
AB  - PURPOSE: To clarify whether and when neuroblastomas identified through screening
      do regress, and to ascertain how to treat them appropriately, we observed
      screened patients who had localized tumors, without any therapeutic intervention.
      PATIENTS AND METHODS: The criteria for the observation program were as follows:
      disease stage I or II; tumor less than 5 cm in diameter; no invasion to the
      intraspinal canal or growth to the great vessels; urinary vanillylmandelic acid
      (VMA) and homovanillic acid (HVA) less than 50 microg/mg creatinine; and informed
      consent. Of 25 patients identified through screening for 6-month-old infants in
      Saitama Prefecture, Japan between April 1994 and March 1996, 11 patients who met
      the criteria and one other patient with stage III tumor were enrolled onto the
      program. They were examined by abdominal ultrasonography (US) and their urinary
      VMA and HVA levels were assessed approximately once per month. The observation
      periods ranged from 4 to 27 months. RESULTS: The 11 tumors decreased in size,
      although one of these 11 tumors initially enlarged until the patient was 12
      months of age and decreased in size thereafter. One other tumor slightly
      increased in size. Urinary VMA levels decreased in all patients. None of the
      tumors had completely disappeared by the last observation day. CONCLUSION: Our
      results suggest that regression of screened neuroblastoma is not a rare
      phenomenon. At present, it seems reasonable to adopt a wait-and-see strategy,
      with careful observation, for selected stage I or II tumors identified in infants
      screened at 6 months of age.

PMID- 9552025
TI  - Frequency and clinical significance of cytogenetic abnormalities in pediatric T
      lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.
AB  - PURPOSE: Nonrandom chromosomal translocations are frequently observed in
      pediatric patients with acute lymphoblastic leukemia (ALL). Specific
      translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL
      patients who have an increased risk of treatment failure. The current study was
      conducted to determine the prognostic significance of chromosomal translocations
      in T-lineage ALL patients. MATERIALS AND METHODS: The study included 169 children
      with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk
      adjusted protocols of the Children's Cancer Group (CCG) who had centrally
      reviewed cytogenetics data. Outcome analyses used standard life-table methods.
      RESULTS: Presenting features for the current cohort were similar to those of
      concurrently enrolled patients for whom cytogenetic data were not accepted on
      central review. The majority of patients (80.5%) were assigned to CCG protocols
      for high-risk ALL and 86.4% had pseudodiploid (n = 80) or normal diploid (n = 66)
      karyotypes; modal chromosome number was not a significant prognostic factor.
      Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with
      del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with
      11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36
      breakpoints. Thirteen patients had the specific 14q11 translocation
      t(11;14)(p13;q11) and all were classified as poor risk. Patients with any of
      these translocations had outcomes similar to those with normal diploid
      karyotypes. CONCLUSION: Chromosomal abnormalities, including specific nonrandom
      translocations, were frequently observed in a large group of children with T
      lineage ALL, but were not significant prognostic factors for this cohort. Thus,
      contemporary intensive treatment programs result in favorable outcomes for the
      majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and
      such features do not identify patients at higher risk for relapse.

PMID- 9552026
TI  - Alternative and complementary therapy use in pediatric oncology patients in
      British Columbia: prevalence and reasons for use and nonuse.
AB  - PURPOSE: Alternative and complementary therapies are infrequently studied in
      pediatric populations. We performed a population-based survey to aid health care
      workers in identifying and counseling parents who may use these remedies.
      PATIENTS AND METHODS: We retrospectively surveyed the parents of 583 pediatric
      patients diagnosed with cancer in British Columbia between 1989 and 1995.
      Prevalence and factors that influence the use and nonuse of alternative and
      complementary therapies were estimated. RESULTS: Alternative and complementary
      therapies were used by 42% of 366 respondents. Herbal teas, plant extracts, and
      therapeutic vitamins were the most commonly used alternative therapies.
      Relaxation/imagery strategies, massage, and therapeutic touch were the most
      commonly used complementary techniques. Factors that influenced the use of
      alternative/complementary therapies were prior use (chi2 = 60.0, P < .0001),
      prior positive attitude towards these remedies (chi2 = 41.6, P < .0001),
      soliciting information from family and friends (chi2 = 70.5, P < .0001) or from
      alternative care givers (chi2 = 58.7, P < .0001), high risk of death at diagnosis
      (chi2 = 9.6, P < .002), and advanced education of the father (chi2 = 7.4, P <
      .006) or mother (chi2 = 8.6, P < .003). Parents who used
      alternative/complementary therapies did so in conjunction with conventional
      medicine (98%). Lack of knowledge and fear of interference with conventional
      therapies were the most common reasons cited for nonuse. No parent believed that
      the quality of life of their child deteriorated due to the use of
      alternative/complementary therapies. CONCLUSION: Alternative and complementary
      therapy use in pediatric oncology patients is common. Factors have been
      identified that may be associated with undertaking their use.

PMID- 9552027
TI  - Randomized comparison of cisplatin and etoposide and either bleomycin or
      ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern
      Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia
      Group B Study.
AB  - PURPOSE: To compare standard therapy with bleomycin, etoposide, and cisplatin
      (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as
      primary treatment of men with advanced, disseminated germ cell tumors. PATIENTS
      AND METHODS: A total of 304 men with advanced disseminated germ cell tumors were
      randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine
      patients were assessable for toxicity and 286 were assessable for response.
      Complete response rates, favorable response (complete remission, surgical free of
      disease, continuous partial remission for 2+ years), time to treatment failure,
      and overall survival were assessed. RESULTS: Overall complete remission rate
      (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free
      at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%)
      were not significantly different between the two treatments. Grade 3 or worse
      toxicity, particularly hematologic and genitourinary toxicity, was significantly
      more common in patients who received VIP. CONCLUSION: BEP and VIP produce
      comparable favorable response rate and survival in patients with poor-risk germ
      cell tumors. The substitution of ifosfamide for bleomycin, however, was
      associated with significantly greater toxicity. Four courses of BEP remain the
      standard treatment for advanced disseminated germ cell tumors.

PMID- 9552028
TI  - Management strategies and outcomes of germ cell tumor patients with very high
      human chorionic gonadotropin levels.
AB  - PURPOSE: To determine the therapeutic results in advanced germ cell tumor (GCT)
      patients with initial human chorionic gonadotropin (hCG) elevation greater than
      50,000 mIU/mL and to document the levels of hCG decline and subsequent plateau
      and outcome of this patient population. PATIENTS AND METHODS: We conducted a
      retrospective review of 41 patients who presented to Indiana University (IU) with
      hCG levels greater than 50,000 mIU/mL between December 1976 and August 1996. All
      patients had received cisplatin-containing regimens and were monitored with
      serial hCG levels. RESULTS: Twenty-two of 41 (53.7%) patients continuously show
      no evidence of disease (NED) and eight additional patients (19.5%) are currently
      NED with salvage therapy. Only two of 41 patients had a normal hCG level at the
      start of the fourth and final course of cisplatin combination chemotherapy. Eight
      additional patients showed normalized hCG levels 1 month later. Seven of these 10
      are continuously NED and three are currently NED with salvage therapy. Thirty-one
      patients had an abnormal hCG greater than 1 month after they completed primary
      chemotherapy; 15 of these patients (48%) are continuously NED despite no further
      therapy and five additional patients (16%) are currently NED with salvage
      therapy. Overall, there was an initial rapid decline in hCG followed by a plateau
      after the first two courses of therapy. CONCLUSION: Less than 10% of patients who
      present with hCG levels greater than 50,000 mIU/mL will have a normal hCG at the
      institution of the fourth and final course of chemotherapy. However, 22 of 41
      (53.7%) are continuously NED despite no further therapy. We feel that the optimal
      strategy for such patients is monthly observation with initiation of salvage
      therapy if and when there is serologic progression.

PMID- 9552029
TI  - Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer:
      ten-year outcome.
AB  - PURPOSE: To evaluate the 10-year outcome of patients with invasive (T2-3N0M0,
      staged according to the tumor, node, metastasis system) bladder cancer who
      responded completely to a combination of methotrexate, vinblastine, adriamycin,
      and cisplatin (MVAC) chemotherapy followed by bladder-sparing surgery. PATIENTS
      AND METHODS: Of 111 surgical candidates who received neoadjuvant MVAC, 60 (54%)
      achieved a complete clinical response (T0) on transurethral resection (TUR) of
      the primary tumor site. Of these, 28 requested follow-up with TUR alone, 15 had a
      partial cystectomy, and 17 elected a radical cystectomy. The patients were
      followed up for a median of 10 years (range, 8 to 13 years). RESULTS: Of 43
      patients who had bladder-sparing surgery, 32 (74%) are alive, which includes 25
      (58%) with an intact functioning bladder. Twenty-four patients (56%) developed
      bladder tumor recurrences from 5 to 96 months, which were invasive in 13 (30%)
      and superficial in 11 (26%). Thirteen patients required a salvage cystectomy, of
      whom 6 died, which includes 4 (9%) from a new invasive neoplasm. Of the 17
      patients who had radical cystectomy, 11 (65%) are alive. CONCLUSION: The majority
      of patients with invasive bladder tumors who achieve T0 status after neoadjuvant
      MVAC chemotherapy preserve their bladders for up to 10 years with bladder-sparing
      surgery. The bladder remains at risk for new invasive tumors. Cystectomy salvages
      the majority, but not all, of relapsing patients.

PMID- 9552030
TI  - Correlation of p34cdc2 cyclin-dependent kinase overexpression, CD44s
      downregulation, and HER-2/neu oncogene amplification with recurrence in prostatic
      adenocarcinomas.
AB  - PURPOSE: To test whether p34cdc2 overexpression, CD44s downregulation, and HER
      2/neu amplification correlate with disease recurrence after radical
      prostatectomy, and to evaluate a possible biologic association between p34cdc2
      and HER-2/neu expression. MATERIALS AND METHODS: Immunohistochemical (IHC)
      detection of both p34cdc2 cyclin-dependent kinase (CDK) and CD44s expression and
      fluorescence in situ hybridization (FISH)-based analysis of HER-2/neu gene status
      were performed on formalin-fixed, paraffin-embedded sections of 106 prostatic
      adenocarcinomas (PACs). Findings were correlated with Gleason grade, pathologic
      stage, DNA ploidy, and postsurgical biochemical disease recurrence. RESULTS: CDK
      overexpression correlated with tumor grade (P = .001), DNA ploidy (P = .001),
      pathologic stage (P = .04), and disease recurrence (P = .01). CD44s
      downregulation correlated with grade (P = .03), ploidy (P = .01), and recurrence
      (P = .02). HER-2/neu amplification correlated with grade (P = .001), ploidy (P =
      .001), and recurrence (P = .01). On multivariate analysis, CDK overexpression
      independently predicted recurrence (P = .001) after prostatectomy. CDK expression
      correlated with HER-2/neu status with 32 of 65 (49%) tumors that overexpressed
      CDK and showed concomitant HER-2/neu amplification (P = .04). CONCLUSION: This
      study showed that p34cdc2, CD44s, and HER-2/neu are variably expressed or
      amplified in prostatic carcinoma and that such alteration may affect tumor
      behavior. In addition, CDK overexpression and HER-2/neu amplification may be
      biologically related.

PMID- 9552031
TI  - Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal
      cancer: phase III randomized Intergroup study 0099.
AB  - PURPOSE: The Southwest Oncology Group (SWOG) coordinated an Intergroup study with
      the participation of Radiation Therapy Oncology Group (RTOG), and Eastern
      Cooperative Oncology Group (ECOG). This randomized phase III trial compared
      chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal
      cancers. MATERIALS AND METHODS: Radiotherapy was administered in both arms: 1.8-
      to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of
      70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on
      days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with
      cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was
      administered every 4 weeks for three courses. Patients were stratified by tumor
      stage, nodal stage, performance status, and histology. RESULTS: Of 193 patients
      registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for
      primary analysis for survival and toxicity. The median progression-free survival
      (PFS) time was 15 months for eligible patients on the radiotherapy arm and was
      not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus
      69%, respectively (P < .001). The median survival time was 34 months for the
      radiotherapy group and not reached for the chemo-radiotherapy group, and the 3
      year survival rate was 47% versus 78%, respectively (P = .005). One hundred
      eighty-five patients were included in a secondary analysis for survival. The 3
      year survival rate for patients randomized to radiotherapy was 46%, and for the
      chemoradiotherapy group was 76% (P < .001). CONCLUSION: We conclude that
      chemoradiotherapy is superior to radiotherapy alone for patients with advanced
      nasopharyngeal cancers with respect to PFS and overall survival.

PMID- 9552032
TI  - Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and
      neck cancer: a randomized multicenter study.
AB  - PURPOSE: A prospective randomized multicenter trial was performed to evaluate the
      contribution of simultaneously administered chemotherapy (CT) and radiotherapy
      (RT) in previously untreated patients with unresectable stage III/IV head and
      neck cancer. PATIENTS AND METHODS: Patients with locoregionally advanced head and
      neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT
      (RCT; arm B). RT was identical in both arms and administered in three courses
      with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to
      11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5
      FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v.
      bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and
      LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5.
      Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was
      administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to
      43. RESULTS: From 1989 to 1993, 298 patients were enrolled and 270 patients were
      assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in
      arm A (16%) (P < .001). Total treatment time was significantly longer in arm B
      than in arm A (P < .001) due to prolonged breaks. According to hematologic
      toxicity, scheduled drug doses were given in 74% of patients for the second
      course and 46% for the third course. The 3-year overall survival rate was 24% in
      arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17%
      in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure
      patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not
      significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not
      significant). CONCLUSION: Concomitant CT offered improved disease control and
      survival in advanced head and neck cancer patients. Due to increased acute
      toxicity, more supportive care is demanded when CT is given simultaneously.
      Increased total treatment time does not exert a negative impact on outcome in
      this combined modality regimen.

PMID- 9552033
TI  - Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with
      recurrent head and neck squamous cell carcinoma.
AB  - PURPOSE: To assess the activity and toxicity profile of combined taxol
      (paclitaxel), ifosfamide, and platinum (cisplatin) (TIP) in patients with
      recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck.
      PATIENTS AND METHODS: Recurrent or metastatic head and neck SCC patients received
      paclitaxel 175 mg/m2 in a 3-hour infusion on day 1; ifosfamide 1,000 mg/m2 in a 2
      hour infusion on days 1 through 3; mesna 600 mg/m2 on days 1 through 3; and
      cisplatin 60 mg/m2 on day 1, repeated every 3 to 4 weeks. All were premedicated
      with dexamethasone, diphenhydramine, and cimetidine. Prophylactic hematopoietic
      growth factors were not permitted. RESULTS: Fifty-two patients were assessable
      for response and toxicity; 53 for survival (local-regional recurrence alone in
      57% and distant metastasis with or without local-regional recurrence in 43%).
      Overall response rate was 58% (30 of 52) of patients; complete response rate was
      17% (nine of 52) of patients, with six complete responses that continued for a
      median 15.7+ months. Median follow-up of all patients was 17.7 months. Median
      survival was 8.8 months (95% confidence interval [CI] 8.1 to 17.5 months).
      Toxicity was relatively well tolerated and caused no deaths. The most frequent
      moderate-to-severe toxicity (90% of patients) was transient grades 3 to 4
      neutropenia; neutropenic fever occurred in 27%. Grade 3 peripheral neuropathy
      occurred in three patients, none had grade 4. Grade 3 mucositis occurred in only
      one patient, none had grade 4. CONCLUSION: TIP had major activity in this
      setting, with a 58% objective response rate, 17% complete response rate, durable
      complete responses (six of nine persisting), and relatively well-tolerated
      toxicity, with no toxic deaths. The activity of TIP, a novel taxol-cisplatin
      based regimen, in recurrent or metastatic head and neck SCC should be confirmed
      in a phase III trial.

PMID- 9552034
TI  - Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin
      for squamous cell carcinoma of the head and neck: a phase I/II trial.
AB  - PURPOSE: A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and
      leucovorin (TPFL5) induction chemotherapy for patients with locally advanced
      squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS:
      Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern
      Cooperative Oncology Group functional status less than or equal to 2 were treated
      with TPFL5. Postchemotherapy home support included intravenous fluids,
      prophylactic antibiotics, and granulocyte colony-stimulating factor (G-CSF).
      Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD).
      Fifteen patients were treated with three cycles of TPFL5 at MTD. Patients who
      achieved either a partial response (PR) or complete response (CR) to three cycles
      of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and
      clinical and pathologic response to TPFL5 were assessed. RESULTS: Twenty-three
      patients received a total of 69 cycles of TPFL5. The MTD was determined to be
      docetaxel 60 mg/m2. Dose-limiting toxicity (DLT) was neutropenia. Additional
      significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral
      neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5
      was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%)
      clinical PRs. Primary-site clinical and pathologic CR rates were 19 of 22 (86%)
      CRs and 20 of 22 (91%) CRs, respectively. Eight patients had less than a CR in
      the neck to chemotherapy and, therefore, had postradiation neck dissections, four
      of which were positive for residual tumor. CONCLUSION: TPFL5 is a tolerable
      induction regimen in patients with good performance status. The DLT is
      neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and
      sodium-wasting nephropathy. The high response rates to TPFL5 justify further
      evaluation of this combination of agents in the context of formal clinical
      trials.

PMID- 9552035
TI  - neu/erbB-2 amplification identifies a poor-prognosis group of women with node
      negative breast cancer. Toronto Breast Cancer Study Group.
AB  - PURPOSE: It remains a challenge to predict which women with axillary node
      negative (ANN) breast cancer at greatest risk of relapse may benefit most from
      adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer
      prognosis. Although overexpression has been investigated extensively, this study
      represents the first prospective assessment of the prognostic value of neu/erbB-2
      DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A
      consecutive series of women was monitored for recurrence (median follow-up
      duration, 36 months) and tumors from 580 individuals were analyzed for
      amplification. The association of amplification with risk of recurrence was
      examined in survival analyses with traditional and histologic markers as
      prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found
      an increased risk of disease recurrence when neu/erbB-2 was amplified > or =
      twofold that persisted with adjustment for other prognostic factors (relative
      risk, 2.36; P = .002). We found some evidence that amplification was more
      important in patients who received chemotherapy compared with untreated patients.
      CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk
      of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2
      amplification have a good prognosis; aggressive therapy in this group is
      therefore difficult to justify. On the other hand, even with adjuvant
      chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification
      have an increased risk of recurrence. We encourage a randomized trial to compare
      more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women
      whose tumors exhibit neu/erbB-2 amplification.

PMID- 9552036
TI  - Randomized phase II trial of infusional fluorouracil, epirubicin, and
      cyclophosphamide versus infusional fluorouracil, epirubicin, and cisplatin in
      patients with advanced breast cancer.
AB  - PURPOSE: We previously developed an inpatient regimen that consisted of
      infusional fluorouracil (5-FU), epirubicin, and cisplatin (ECisF), with a
      response rate of 86% in advanced breast cancer. The current phase II 2:1
      randomized study investigated whether cyclophosphamide can be substituted for
      cisplatin (ECycloF) to reduce toxicity and allow the regimen to be administered
      on an outpatient basis without loss of efficacy. PATIENTS AND METHODS: Ninety-six
      women (median age, 49 years; range, 28 to 73) with breast cancer (59 metastatic,
      37 locally advanced) received continuous infusional 5-FU (200 mg/m2/d via Hickman
      line) and six cycles of epirubicin (60 mg/m2 every 21 days) with either
      cyclophosphamide 600 mg/m2 every 21 days (38 metastatic, 24 locally advanced) or
      cisplatin 60 mg/m2 every 21 days (21 metastatic, 13 locally advanced). There were
      no significant differences in patient characteristics between these groups.
      RESULTS: ECycloF was better tolerated than ECisF in terms of lethargy (P = .005),
      stomatitis (P = .008), plantar palmar erythema (P = .02), constipation (P <
      .001), thrombosis (P = .0014), and nausea and vomiting (P = .05). Although there
      was a trend toward more anemia and leukopenia with ECisF (P =. 1), there was no
      significant difference in the rates of infection. Efficacy was comparable in
      terms of overall response (69% v 68%), complete response (CR; 13% v 15%), and
      median progression-free survival (9 v 8 months). CONCLUSION: ECycloF is an
      outpatient regimen with a lower incidence of severe nonhematologic toxicity than
      inpatient ECisF; it has comparable efficacy and is considerably more economical.

PMID- 9552037
TI  - Adjuvant chemoendocrine therapy in postmenopausal breast cancer:
      cyclophosphamide, methotrexate, and fluorouracil dose and schedule may make a
      difference. International Breast Cancer Study Group.
AB  - PURPOSE: Adjuvant cytotoxics prolong disease-free survival (DFS) and overall
      survival (OS) in patients with operable breast cancer. The first reported
      effective adjuvant combination regimen consisted of oral cyclophosphamide on days
      1 to 14 with intravenous methotrexate and fluorouracil on days 1 and 8, repeated
      every 28 days (classical CMF). These drugs have since been extensively used with
      or without endocrine therapies and/or other cytotoxic agents. Although doses and
      schedules have varied widely, the combination of these three drugs is generically
      referred to as CMF. RESULTS: Reducing the dose and/or altering the schedule of
      CMF have compromised its efficacy in metastatic breast cancer. Reduction below
      standard dose of a similar regimen also gave inferior results in the adjuvant
      setting. CONCLUSION: Details of dose and schedule may therefore explain part of
      the heterogeneity of results observed with CMF. Particular controversy surrounds
      the contribution of CMF in postmenopausal women who are also receiving tamoxifen
      (TAM). However, the trials that demonstrated a significant benefit for the
      addition of CMF to TAM, even in postmenopausal women with estrogen receptor
      positive tumors, used classical CMF. Therefore, adherence to the classical dose
      and schedule is recommended when CMF is used in adjuvant therapy.

PMID- 9552038
TI  - Early breast cancer: evaluation of the prognostic role of the site of the primary
      tumor.
AB  - PURPOSE: The prognostic role of the site of the primary breast cancer has not
      been clarified. This study aimed to gather more information about this issue from
      a large series of patients with long-term follow-up data. PATIENTS AND METHODS:
      Data from 2,396 patients treated for early breast cancer with a conservative
      approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral
      site, while in 777 cases, it was situated in the internal/central quadrants. The
      characteristics of the two groups were well balanced, apart from axillary nodal
      metastases, which were more frequent for lateral tumors (38.1% v 26.3%). RESULTS:
      Analysis of distant metastases indicated that the regression coefficient
      associated with tumor site was significant and the hazards ratio estimate was
      1.291, which indicates the risk of distant metastases was increased by
      approximately 30% for internal/central tumors. The analysis of overall survival
      yielded a significant coefficient and a hazards ratio of 1.192, which indicates
      an approximately 20% increase of mortality for internal/central tumors.
      CONCLUSION: Early breast cancers situated in central/ internal quadrants have a
      worse prognosis compared with those in lateral quadrants, in terms of distant
      metastases and survival. Irradiation of the internal mammary chain for
      internal/medial tumors could be suggested, but, to date, the therapeutic strategy
      is still controversial.

PMID- 9552039
TI  - Outcome after invasive local recurrence in patients with ductal carcinoma in situ
      of the breast.
AB  - PURPOSE: To detail the outcome, in terms of local recurrence, local invasive
      recurrence, distant recurrence, and breast cancer mortality for patients
      previously treated for ductal carcinoma in situ (DCIS). PATIENTS AND METHODS:
      Clinical, pathologic, and outcome data were collected prospectively for 707
      patients with DCIS accrued from 1972 through June 1997. RESULTS: There were 74
      local recurrences; 39 were noninvasive (DCIS) and 35 were invasive. Fifty-one
      percent of patients with invasive recurrences presented with stage 1 disease; the
      remainder presented with more advanced disease. Invasive local recurrence after
      mastectomy was a rare event that occurred in 0.8% of patients. Invasive
      recurrence after breast preservation was more common and occurred in 7.4% of
      patients. The 8-year probability of breast cancer mortality after breast
      preservation was 2.1%, a number that is likely to increase with longer follow-up.
      The 8-year breast cancer-specific mortality and distant-disease probability for
      the subgroup of 74 patients with locally recurrent disease was 8.8% and 20.8%,
      respectively. If only the 35 invasive recurrences are considered as events, the 8
      year breast cancer-specific mortality and distant-disease probability was 14.4%
      and 27.1%, respectively. CONCLUSION: Invasive local recurrence after breast
      preservation treatment for patients with DCIS is a serious event that converts
      patients with previous stage 0 disease to patients with disease that ranges from
      stage I to stage IV. These results, however, indicate that most DCIS patients
      with local recurrence can be salvaged.

PMID- 9552040
TI  - No long-term increase in cardiac-related mortality after breast-conserving
      surgery and radiation therapy using modern techniques.
AB  - PURPOSE: To determine whether left-breast irradiation using modern techniques
      after breast-conserving surgery leads to an increased risk of cardiac-related
      mortality. METHODS: Between 1968 and 1986, 1,624 patients were treated for
      unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy,
      Harvard Medical School, Boston, MA, with conservative surgery and breast
      irradiation. Seven hundred forty-five patients with a potential follow-up of at
      least 12 years were analyzed. Clinical, pathologic, and treatment characteristics
      were compared between the 365 patients (49%) who received left-sided irradiation
      and the 380 patients (51%) who received right-sided irradiation. The relationship
      between left-sided breast irradiation and the risk of nonbreast cancer- and
      cardiac-related mortality was examined. RESULTS: There was no significant
      difference in the distribution of clinical, pathologic, or treatment
      characteristics between the two groups, with the exception of a small difference
      in pathologic tumor size (medians, left, 2.0 cm, right, 1.5 cm; P = .007). At 12
      years, a majority of patients still were alive. Slightly more patients with left
      sided tumors had died of breast cancer (31% v 27%; P = NS). Equivalent
      proportions from each group died of nonbreast cancer causes (11%), including nine
      patients (2%) from each group who died from cardiac causes. The risk of cardiac
      mortality did not increase as time after treatment increased for patients who
      received left-sided irradiation compared with right-sided irradiation. A model
      that controlled for clinical, pathologic, and treatment differences showed no
      significant increase in any category of cause of death (breast, cardiac, or
      other) for patients who received left-sided irradiation. CONCLUSION: These
      results suggest that modern breast radiotherapy is not associated with an
      increased risk of cardiac-related mortality within at least the first 12 years
      after treatment.

PMID- 9552041
TI  - Quality of life and preferences for treatment following systemic adjuvant therapy
      for early-stage breast cancer.
AB  - PURPOSE: To evaluate the quality of life (QOL) of breast cancer patients who
      survived 2 to 5 years following initiation of adjuvant cytotoxic and/or hormonal
      therapy and to characterize relationships between QOL and patient physical
      symptoms, sexual function, and preferences regarding adjuvant treatment. PATIENTS
      AND METHODS: Eighty-six patients who had completed systemic adjuvant therapy for
      early-stage breast cancer between 1988 and 1991 were surveyed by written
      questionnaire and telephone interview. Sociodemographic information was obtained
      for each patient, and patients were asked to complete the Functional Living Index
      Cancer (FLIC), the Symptom Distress Scale (SDS), the Medical Outcomes Study (MOS)
      Short Form 36 (SF-36), a series of questions regarding sexual function, and a
      survey about preferences for adjuvant therapy in relation to possible benefit.
      RESULTS: The mean FLIC score among all patients was 138.3 (+/- 12.2), which
      suggests a high level of QOL. The reported frequency of moderate to severe
      symptoms was generally low (ie, < 15%), with fatigue (31.4%), insomnia (23.3%),
      and local numbness at the site of surgery (22.1%) occurring with greatest
      frequency. Patients reported a wide range of sexual difficulties. Preference
      assessment showed that more than 65% of patients were willing to undergo 6 months
      of chemotherapy for a 5% increase in likelihood of cancer cure. CONCLUSION: Self
      rated QOL in breast cancer patients 2 to 5 years following adjuvant therapy was
      generally favorable. Less than one third of patients reported moderate to severe
      symptoms. Selected aspects of sexual function appeared to be compromised. The
      majority of patients indicated a willingness to accept 6 months of chemotherapy
      for small to modest potential benefit.

PMID- 9552042
TI  - Phase III randomized trial comparing cisplatin and carboplatin with or without
      ifosfamide in patients with advanced non-small-cell lung cancer. European Lung
      Cancer Working Party.
AB  - PURPOSE: A phase III randomized trial in patients with advanced non-small-cell
      lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to
      moderate-dose cisplatin and carboplatin improved response rate (primary end
      point) and survival. PATIENTS AND METHODS: A total of 529 patients were
      randomized to receive a combination of moderate-dose carboplatin (200 mg/m2
      intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with
      (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There
      were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238
      patients assessable for response, respectively. All but 23 had stage IV disease
      with pleural effusion. RESULTS: There was a 16% objective response (OR) rate to
      CC and a 31% OR rate to CCI. That observed difference was highly statistically
      significant (P < 0.001). Duration of response and survival were not statistically
      different between arms. The CCI regimen was associated with significantly more
      acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The
      frequency of chronic renal, auditive, and peripheral neurologic toxicity was low
      in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy).
      The relative dose-intensity (RDI) of the CCI arm was significantly lower than
      that of the CC arm. CONCLUSION: The addition of ifosfamide to moderate-dose
      cisplatin and carboplatin significantly improves the antitumoral response rate,
      but has no apparent effect an survival in advanced NSCLC.

PMID- 9552043
TI  - Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and
      KAI1/CD82 gene expression.
AB  - PURPOSE: The transmembrane-4 superfamily (TM4SF) is a recently discovered family
      of genes. Of the TM4SF members, MRP-1/CD9, KAI1/CD82, and ME491/CD63 have been
      reported to modulate tumor progression or metastasis. In this study, we
      investigated the relationships between these three genes, MRP-1, KAI1, and ME491,
      in patients with non-small-cell lung cancers (NSCLCs). Moreover, we assessed the
      prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491
      simultaneously in NSCLCs. PATIENTS AND METHODS: One hundred seventy-two patients
      up to stage IIIB NSCLC underwent radical surgery during the period of January
      1991 through June 1994. Using a quantitative reverse-transcriptase polymerase
      chain reaction (RT-PCR) analysis, we studied the expression of MRP-1, KAI1, and
      ME491 genes in these patients. RESULTS: We found that 109 patients (63.4%) had
      MRP-1-positive tumors and 42 patients (24.4%) had KAl1-positive tumors.
      Conversely, all 172 patients expressed ME491. No relationship was found between
      MRP-1 expression and KAI1 expression. We classified these patients into three
      groups. The 36 patients who were positive for both MRP-1 and KAI1 were defined as
      group A; the 79 patients with reduced expression of either MRP-1 or KAI1 were
      defined as group B, and the remaining 57 patients with reduced expression of both
      MRP-1 and KAI1 were defined as group C. This new classification was correlated
      with nodal status, tumor status, and pathologic stage (P = .0056, P = .0003, and
      P < .0001, respectively). In NSCLC patients, the 5-year survival rate of group A
      patients was significantly better than that of group B patients and much better
      than that of group C patients (86.8%, 53.9%, and 31.5%, respectively; P < .0001).
      Cox multivariate regression analysis showed that this new classification in
      NSCLCs was a significant prognostic factor, as was the nodal status (P < .0001).
      CONCLUSION: Our results suggest that a low MRP-1 and KAI1 expression by tumors of
      the lung may be associated with poor prognosis. It is conceivable that the
      evaluation for MRP-1 and KAI1 expression may identify node-negative lung cancer
      patients who are at high risk for early disease recurrence, and thus need
      intensive adjuvant therapy.

PMID- 9552044
TI  - Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets
      of patients with non-small-cell lung cancer.
AB  - PURPOSE: Plakoglobin is thought to play a key role in cadherin-mediated
      epithelial cell adhesion, because it is a common component of desmosomal and
      nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an
      important early step in invasion and metastasis of solid tumors, we evaluated the
      frequency and prognostic significance of a deficient expression of plakoglobin in
      human lung cancer. PATIENTS AND METHODS: At primary surgery, representative
      specimens of the primary tumor were obtained from 96 consecutive patients with
      completely resected non-small-cell lung carcinoma (NSCLC) without overt distant
      metastases. Cryostat sections of these specimens and metastatic lymph nodes were
      stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an
      immunoperoxidase technique. Patients were monitored for a median of 39 months
      (range, 12 to 56) after surgery. RESULTS: Absent or severely reduced expression
      of plakoglobin (ie, < 30% positive tumor cells) was observed in 39 patients
      (40.6%). There was no significant correlation to established risk factors, such
      as the histology, extension, and histologic grade of the primary tumor and
      metastatic lymph node involvement, or expression of alpha-catenin. Expression of
      plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive
      tumor cells. Deficient plakoglobin expression on the primary tumor was
      significantly correlated to a shortened disease-free and overall survival in
      patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In
      patients with pT1-2 tumors, the independence of this prognostic influence from
      established risk factors was demonstrated by Cox regression analyses (disease
      free survival, P = .002; overall survival, P = .038). CONCLUSION: Deficient
      expression of plakoglobin appears to be an important event in the progression of
      NSCLC.

PMID- 9552045
TI  - Carboplatin plus vinorelbine, a new well-tolerated and active regimen for the
      treatment of extensive-stage small-cell lung cancer: a phase II study. Gruppo
      Oncologico Centro-Sud-Isole.
AB  - PURPOSE: To evaluate the activity and toxicity of the combination carboplatin
      plus vinorelbine in extensive small-cell lung cancer (SCLC). PATIENTS AND
      METHODS: A two-stage optimal Simon design was applied. To proceed after the first
      stage, responses from 8 of 11 treated patients were needed. Overall, 31 responses
      of 43 treated patients were required to comply with the design parameters.
      Inclusion criteria were cytohistologically proven SCLC; extensive disease; age of
      70 years or less; Eastern Cooperative Oncology group performance status (ps ECOG)
      of 2 or less; normal cardiac, hepatic, renal, and bone marrow functions; and no
      previous chemotherapy. Patients were staged by physical examination;
      biochemistry; chest radiograph; brain, thoracic; and abdominal computed
      tomographic (CT) scans, and bone scan. All patients received carboplatin 300
      mg/m2 intravenously (i.v.) day 1 and vinorelbine 25 mg/m2 i.v. on days 1 and 8
      every 4 weeks up to six cycles. Of 43 enrolled patients, 36 were men and 7 women,
      with a median age of 63 years (range, 46 to 70 years). RESULTS: All patients were
      assessable for response and toxicity. We observed 32 (74%) objective responses,
      with 23% complete responses. Median time to progression was 25 weeks, and median
      survival was 37 weeks. The treatment was well tolerated. The reported main
      toxicities were leukopenia grade 3 in 21% of patients and grade 4 in 5% of
      patients, anemia grade 2 in 11% of patients and grade 3 in 2% of patients, and
      thrombocytopenia grade 3 in 7% of patients. CONCLUSION: These data show that
      carboplatin plus vinorelbine is an active and well-tolerated regimen in extensive
      SCLC. In view of the activity, low toxicity, and ease of administration, it may
      be a reasonable alternative to more toxic cisplatin-containing regimens.

PMID- 9552046
TI  - Costs of care associated with non-small-cell lung cancer in a commercially
      insured cohort.
AB  - PURPOSE: To examine the cost of incident cases of non-small-cell lung cancer
      (NSCLC) in a commercially insured cohort. METHODS: Claims from Virginia Blue
      Cross and Blue Shield (BCBS) beneficiaries with lung cancer from 1989 to 1991
      were merged with records from the Virginia Cancer Registry (VCR). Data from the
      VCR identified incident cases, stage, and type of cancer at diagnosis. Costs for
      all medical care included insurance payment, copayments, and deductibles for 2
      years after diagnosis or until death. RESULTS: Three hundred forty-nine incident
      NSCLC patients were evaluated. The mean 2-year cost for each patient after
      diagnosis or until death was $47,941 (95% confidence interval, $43,758 to
      $52,124). Total average costs and hospital days were significantly lower for
      local disease ($37,514, 21.2 days), but were similar for regional ($52,797, 30.0
      days) and distant ($49,382, 33.0 days) disease. Hospital days accounted for 48%
      and hospital-based claims for 70% of costs. Initial treatments, which included
      radiation, unadjusted for stage, had the lowest survival rates and the highest
      costs, and were associated with the most hospital days. Initial stage, race,
      gender, and age were not predictors of total 2-year costs. The independent
      predictors of total 2-year costs were type of treatment: any radiation therapy,
      any surgery, or any chemotherapy (all, P < .001). Inpatient hospital days was
      only a modest predictor of costs after adjusting for type of treatment. Patients
      who survived less than 1 year spent 30.5 days in hospital and had an average cost
      of $47,280. CONCLUSION: The direct health care costs of younger NSCLC patients
      care are substantial. These results should serve as a benchmark for future
      comparisons as the United States market shifts to managed care.

PMID- 9552047
TI  - Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous
      melanoma. Austrian Malignant Melanoma Cooperative Group.
AB  - PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or =
      1.5 mm have only a 30% to 70% probability of survival after surgery, and no
      adjuvant therapy has so far improved this outcome. Since interferon alfa-2a
      (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated
      whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus
      prolongs disease-free survival in melanoma patients after excision of the primary
      tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma
      patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant
      IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the
      primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously
      (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three
      times per week was given over 1 year (maintenance phase). RESULTS: Prolonged
      disease-free survival was observed in patients treated with IFNalpha2a versus
      those who underwent surgery alone. This difference was significant (P = .02) for
      all patients enrolled onto the study (intention-to-treat analysis) at a mean
      observation time of 41 months. Subgroup analysis showed that Breslow tumor
      thickness had no influence on treatment results in the groups of patients
      investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence
      of metastases and thus prolongs disease-free survival in resected primary stage
      II cutaneous melanoma patients.

PMID- 9552048
TI  - Is the survival of melanoma patients receiving polyvalent melanoma cell vaccine
      linked to the human leukocyte antigen phenotype of patients?
AB  - PURPOSE: An allogeneic polyvalent melanoma cell vaccine (PMCV) has been shown to
      be efficacious in improving overall survival of patients with malignant melanoma
      in a phase II clinical setting. The PMCV consists of three allogeneic melanoma
      cell lines. The objectives of the study were to determine (1) whether the
      survival of melanoma patients who received PMCV was related to the patient's
      human leukocyte antigen (HLA) class I phenotype matching the HLA class I
      phenotype of the PMCV, and (2) whether PMCV clinical efficacy was correlated to
      melanoma patients with a particular HLA phenotype(s). MATERIALS AND METHODS: PMCV
      was given to 69 melanoma patients with American Joint Committee on Cancer (AJCC)
      stage I to IV disease status. The PMCV and patients lymphocytes were typed for
      HLA-A and -B. A correlation was made between the HLA expression of PMCV lines and
      the HLA of patients to their survival status. A second correlation was made
      between the HLA of patients and survival independent of the PMCV HLA phenotype.
      RESULTS: Patients whose HLA phenotype (A3/11 and B7/44) matched the PMCV lines
      had a better overall survival (P < .029). Analysis of HLA expression of patients
      independent of PMCV HLA to survival showed that HLA-A25 phenotype patients had a
      significantly better overall survival (P = .006). HLA-B35 patients had a poorer
      survival outcome (P = .019). CONCLUSION: The studies indicate that overall
      survival following PMCV treatment in melanoma patients significantly correlates
      with their HLA phenotypes. These correlations may be related to the host immune
      response to the PMCV or due to differences in the clinical course of melanoma in
      patients with different HLA types.

PMID- 9552049
TI  - Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult
      patients with metastatic or locally advanced soft tissue sarcoma: a phase II
      study.
AB  - PURPOSE: To evaluate the feasibility and toxicity of the combination of full-dose
      epirubicin (EPI) and high-dose ifosfamide (IFO) with granulocyte colony
      stimulating factor (G-CSF) support and to determine the clinical efficacy in
      terms of response and impact on survival. PATIENTS AND METHODS: Forty-six
      consecutive, previously untreated patients with locally advanced or metastatic
      high-grade soft tissue sarcomas were treated with IFO 2.5 g/m2/d as a continuous
      infusion on days 1 to 5 and EPI 45 mg/m2/d as a continuous infusion on days 2 and
      3 every 3 weeks. G-CSF 5 microg/kg/d subcutaneously (s.c.) was given on days 6 to
      15 or until recovery of leukocytes after all cycles. Response evaluation was
      performed every two cycles and responding patients were treated with up to six
      cycles. All patients were evaluated for resectability of residual local or
      metastatic disease and underwent surgery if possible. RESULTS: All patients
      experienced grade 3 or 4 myelosuppression. Other toxicities were mild. The
      overall response rate was 52%, with a complete remission (CR) rate of 22% after
      chemotherapy alone. Eight additional patients were rendered free of tumor (no
      evidence of disease [NED]) by surgical procedures. The median overall survival of
      all patients is 24 months. The CR/NED patients (39%) have a significantly
      superior survival time compared with all other patients. Thirteen of these 18
      patients (72%) are alive, nine free of tumor, with a median follow-up time of 33
      months. CONCLUSION: This dose-intensive combination chemotherapy is toxic but
      feasible and produced a high number of partial remissions (PRs) and especially
      CRs, which resulted in prolonged survival.

PMID- 9552050
TI  - Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical
      Trial Group study. AIDS Clinical Trial Group No. 215 Team.
AB  - PURPOSE: Angiogenesis is a major component of Kaposi's sarcoma (KS) and a
      critical process in tumor growth. The present study was designed primarily to
      test the toxicity and pharmacokinetics (PK) of the angiogenesis inhibitor TNP-470
      and secondarily to evaluate tumor response in patients with early AIDS-related
      KS. PATIENTS AND METHODS: Patients with AIDS-related KS were required to have
      cutaneous disease with > or = 5 measurable lesions and no evidence of pulmonary,
      symptomatic gastrointestinal, or acutely life-threatening KS. Thirty-eight
      patients received TNP-470 by weekly intravenous infusion over 1 hour at one of
      six dose levels for up to 24 weeks. RESULTS: The dose levels tested included 10,
      20, 30, 40, 50 and 70 mg/m2. Median CD4 count was 24 cells/microl (range, 0 to
      460). Fourteen patients (36%) had > or = 50 cutaneous lesions and 19 (49%) had
      oral lesions. Adverse events included neutropenia (n = 2), hemorrhage (n = 3),
      and urticaria (n = 1). PK studies showed wide interpatient and intrapatient
      variability. Elimination half-life values were short (range, 0.01 to 0.61 hours).
      Seven patients (18%) achieved a partial response. The median time to partial
      response was 4 weeks (range, 2 to 25), and the median duration of response was 11
      weeks (range, 3 to 26+). CONCLUSION: TNP-470, administered as a weekly, 1-hour
      infusion to patients with early AIDS-KS is well-tolerated at doses up to and
      including the highest dose tested. Tumor responses were observed in a substantial
      number of cases and occurred at various dose levels. TNP-470 should be evaluated
      further in patients with AIDS-KS as a single agent and in combination with other
      biologic response modifiers in early disease or after initial response to
      cytotoxic chemotherapy.

PMID- 9552051
TI  - Phase I clinical and pharmacologic study of eniluracil plus fluorouracil in
      patients with advanced cancer.
AB  - PURPOSE: To determine the highest dose of fluorouracil (5-FU) that could be
      safely administered with Eniluracil (776C85; Glaxo Wellcome Inc, Research
      Triangle Park, NC), an inactivator of dihydropyrimidine dehydrogenase (DPD), on a
      daily schedule for 5 days, and to define the toxicities of the combination and
      the pharmacokinetics of 5-FU when administered with 776C85. PATIENTS AND METHODS:
      Patients with advanced solid tumors refractory to standard therapy were enrolled
      at two institutions. The study consisted of three periods designed to evaluate
      the safety, pharmacokinetics, and pharmacodynamics of 776C85 alone (period 1);
      the effects of 776C85 on the pharmacokinetics of 5-FU (period 2); and the maximum
      tolerated dose (MTD) of 5-FU, with or without leucovorin, that could be safely
      administered with 776C85 (period 3). Cohorts of at least three patients each
      received oral 776C85 alone at doses of 3.7 mg/m2/d, 18.5 mg/m2/d and 0.74
      mg/m2/d. After a 14-day washout period, each patient then received 776C85 daily
      for 3 days, with a single intravenous (i.v.) bolus dose of 5-FU 10 mg/m2 on day
      2. After a second washout period, patients were treated with 776C85 daily for 7
      days and 5-FU i.v. bolus on days 2 through 6. The starting dose of 5-FU 10
      mg/m2/d was escalated until the MTD was determined. After determination of the
      MTD of 5-FU given with 776C85, oral leucovorin 50 mg/d on days 2 through 6 was
      added to determine the MTD of 5-FU with leucovorin in the presence of 776C85.
      Near the completion of the study, additional cohorts of patients were treated
      with 776C85 at 50 mg/d and oral 5-FU with or without leucovorin. RESULTS: Sixty
      five patients were enrolled onto the study and 60 were assessable for toxicity
      and response. Bone marrow suppression was the primary and dose-limiting toxicity
      of this regimen. Other toxicities included diarrhea, mucositis, anemia, anorexia,
      nausea, vomiting, and fatigue. 776C85 suppressed DPD activity in peripheral-blood
      mononuclear cells (PBMCs) by at least 90% for at least 24 hours at all dose
      levels tested. In the presence of 776C85, 5-FU half-life was prolonged, clearance
      was reduced, and the drug displayed linear pharmacokinetics. Recommended doses
      for further testing on a daily for 5-day schedule are 776C85 10 mg/d with i.v. 5
      FU 25 mg/m2/d; 776C85 10 mg/d with i.v. 5-FU 20 mg/m2/d plus leucovorin 50 mg/d;
      776C85 50 mg/d with 5-FU given orally at 15 mg/m2/d with leucovorin at 50 mg/d.
      CONCLUSION: 5-FU can be safely administered with 776C85; however, the MTDs are
      considerably lower than those conventionally used, caused, at least in part, by
      marked alterations in 5-FU plasma pharmacokinetics.

PMID- 9552052
TI  - Phase I and pharmacokinetic trial of aminopterin in patients with refractory
      malignancies.
AB  - PURPOSE: Aminopterin (AMT) is a potent folate analog that is no longer in routine
      clinical use. Because of laboratory data that suggests improved metabolism of AMT
      versus methotrexate (MTX) in lymphoblasts, we developed a phase I trial to
      determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and
      pharmacokinetic profile of AMT. PATIENTS AND METHODS: Twenty patients with
      refractory malignancies were treated. The starting dose of AMT was 2.5 mg/m2
      every 12 hours for two doses weekly: the dose of AMT was decreased and leucovorin
      (LV) rescue was added after the DLT was observed. Pharmacokinetics were performed
      after both intravenous (i.v.) and oral AMT administration. RESULTS: Mucosal
      toxicity was dose-limiting and resulted in the need for a dose reduction (dose
      level 2: AMT 2 mg/m2 every 12 hours for two doses weekly) and, subsequently, the
      addition of scheduled LV rescue (dose level 3: AMT 2 mg/m2 every 12 hours for two
      doses followed by LV 5 mg/m2 orally every 12 hours for two doses, starting 24
      hours after the second dose of AMT). The mean areas under the curve (AUC) for the
      i.v. (n = 14) and oral (n = 13) doses were 1.20 +/- 0.09 (SE) and 1.05 +/- 0.14
      micromol x h/L respectively. The half-life was 3.64 +/- 0.28 hours and the oral
      bioavailability in 12 matched subjects was 83.5% +/- 8.3%. One patient with
      endometrial adenocarcinoma achieved a complete response (CR) and remains on
      therapy at 11+ months. Seven patients had stable disease (SD) for 8 weeks or
      greater, which included one patient with a metastatic nerve sheath tumor who was
      stable for 9 months. CONCLUSION: We conclude that AMT has good oral
      bioavailability and that, when given on a q12 hour x two weekly schedule, the MTD
      is 2 mg/m2 with delayed LV rescue.

PMID- 9552053
TI  - Higher levels of thymidylate synthase gene expression are observed in pulmonary
      as compared with hepatic metastases of colorectal adenocarcinoma.
AB  - PURPOSE: It has been observed previously that the pulmonary metastases of
      colorectal adenocarcinoma are less responsive to therapy with fluorouracil (FUra)
      as compared with other sites of metastasis (liver, local). To investigate the
      basis of this chemoresistance, the levels of thymidylate synthase (TS) mRNA and
      protein were measured, as TS expression has been shown to be predictive of
      response to therapy in colorectal cancer. MATERIALS AND METHODS: Tumors were
      obtained from 19 patients with metastatic colorectal cancer (12 hepatic and seven
      pulmonary). TS expression was measured by quantitative reverse-transcriptase
      polymerase chain reaction (RT-PCR) and TS protein levels were measured by Western
      blotting. The presence of TS amplification was assessed by Southern blotting.
      Levels of p53 protein were determined using immunohistochemistry. RESULTS: TS
      mRNA expression was shown to be significantly higher in the pulmonary metastases
      (mean TS/beta-actin ratio, 19.7; n = 7) as compared with the hepatic metastases
      (mean TS/beta-actin ratio, 4.7; n = 11) of colorectal cancer. Lower TS expression
      was observed in patients with hepatic metastases who had received prior FUra
      versus patients who had not been treated. High levels of TS expression in some
      samples was associated with low-level (two to three gene copies) increases in TS
      gene copy numbers and this was observed more frequently in the pulmonary
      metastatic samples. The increased gene copy numbers occurred both in samples with
      wild-type p53 and those with mutant p53 tumor-suppressor gene as determined by
      immunohistochemistry. CONCLUSION: High levels of TS enzyme may be the basis of
      the lack of response of pulmonary metastases to FUra treatment.

PMID- 9552054
TI  - Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and
      leucovorin: results of a multicentric prospective trial of fluorouracil dosage
      optimization by pharmacokinetic monitoring in 152 patients.
AB  - PURPOSE: A relationship between fluorouracil (5-FU) dose and response has been
      previously shown in advanced colorectal cancer. In a previous study with 5-FU
      stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we
      defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area
      under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L).
      The current study investigated 5-FU therapeutic intensification with individual
      dose adjustment in a multicentric phase II prospective trial. PATIENTS AND
      METHODS: Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2
      leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according
      to 5-FU plasma levels, to reach the therapeutic range previously determined.
      RESULTS: A total of 152 patients entered the study from December 1991 to December
      1994: 117 patients with measurable metastatic disease and 35 with assessable
      disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot
      syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18
      had a complete response (CR), 48 a partial response (PR), 35 a minor response
      (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall
      survival time was 19 months. The 5-FU therapeutic plasma range was rapidly
      reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386
      mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic
      zone, whereas 51 required a > or = 50% dose increase. CONCLUSION: Individual 5-FU
      dose adjustment with pharmacokinetic monitoring provided a high survival rate and
      percentage of responses, with good tolerance.

PMID- 9552055
TI  - Isolated hepatic perfusion with tumor necrosis factor and melphalan for
      unresectable cancers confined to the liver.
AB  - PURPOSE: To evaluate the efficacy and systemic and regional toxicities of
      hyperthermic isolated hepatic perfusion (IHP) using tumor necrosis factor (TNF)
      and melphalan for the treatment of unresectable primary or metastatic cancers
      confined to the liver. PATIENTS AND METHODS: Thirty-four patients (18 men and 16
      women; mean age, 49 years) underwent a 60-minute hyperthermic (39.5 degrees to
      40.0 degrees C) IHP performed by laparotomy that used TNF 1.0 mg and melphalan
      1.5 mg/kg. Perfusion inflow was through the gastroduodenal artery and outflow was
      from a cannula positioned in an isolated segment of retrohepatic inferior vena
      cava (IVC). Infrahepatic IVC and portal venous blood flow were shunted to the
      axillary vein using an external venoveno bypass circuit. Complete vascular
      isolation of the liver was confirmed by an I-131-labelled human serum albumin
      monitoring technique. RESULTS: There was no operative mortality. Seventy-five
      percent of patients had reversible grade III or IV (National Cancer Institute
      Common Toxicity Criteria) hepatic toxicity with one treatment-related mortality
      (3%) because of hepatic venoocclusive disease. In 33 assessable patients, the
      overall response rate was 75% (complete response, one patient [3%]; partial
      response, 26 patients [72%]). With a median potential follow-up of 15 months, the
      mean duration of response was 9 months (range, 2 to 30 months). CONCLUSION: IHP
      with TNF and melphalan results in significant regression of bulky hepatic cancers
      confined to the liver in the majority of patients. Based on these initial
      results, further refinement of this treatment technique is warranted; perhaps by
      the combination of IHP with other regional treatment strategies to provide long
      term control of unresectable cancers confined to liver.

PMID- 9552056
TI  - Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the
      Italian Gastric Cancer Study Group prospective multicenter surgical study.
AB  - PURPOSE: To investigate whether pancreas preservation together with a strict
      quality-control system could ameliorate the outcome of D2 resections for gastric
      cancer in Western patients. PATIENTS AND METHODS: Italian patients with
      potentially curable proven adenocarcinoma of the stomach were registered from
      nine general and/or university hospitals in the area of Turin, Northern Italy.
      The study was performed according to the guidelines of the Japanese Research
      Society for Gastric Cancer (JRSGC). A strict quality-control system was
      guaranteed by a supervising surgeon of the reference center, who had stayed at
      the National Cancer Center Hospital, Tokyo, to learn the standard D2 gastrectomy.
      The standard procedure entailed removal of the level 1 and 2 lymph nodes. During
      total gastrectomy, the pancreas was preserved according to the Maruyama
      technique. RESULTS: Between May 1994 and December 1996, 191 eligible patients
      were entered onto the study. The mean number of lymph nodes removed was 39. The
      overall morbidity rate was 20.9%. Surgical complications were observed in 16.7%
      of patients. Reoperation was necessary in six patients and was always successful.
      The overall hospital mortality rate was 3.1%; it was higher after total
      gastrectomy (7.46%) than after distal gastrectomy (0.8%). The average length of
      hospital stay was 17 days. CONCLUSION: Given that postoperative morbidity and
      mortality rates are favorably comparable with those reported after the Western
      standard gastrectomy, the more extensive Japanese procedure with pancreas
      preservation can be regarded as a safe radical treatment of gastric cancer for
      selected Western patients treated in experienced centers.

PMID- 9552057
TI  - Second-line therapy with paclitaxel and carboplatin for recurrent disease
      following first-line therapy with paclitaxel and platinum in ovarian or
      peritoneal carcinoma.
AB  - PURPOSE: The combination of paclitaxel and a platinum compound is the most active
      first-line regimen for advanced ovarian carcinoma. The current study was
      undertaken to evaluate this combination in the re-treatment of patients with
      ovarian or peritoneal carcinoma who had disease recurrence > or = 6 months
      following this combination. METHODS: Twenty-five patients with recurrent ovarian
      or peritoneal carcinoma > or = 6 months after a complete clinical response with
      first-line paclitaxel and platinum chemotherapy were studied. Recurrent disease
      was documented by computed tomography (CT), elevated CA 125 level, or surgical
      findings. Second-line chemotherapy consisted of paclitaxel 135 mg/m2 as a 24 hour
      infusion and carboplatin at an area under the concentration-time curve (AUC) of 5
      to 6 every 21 days. Response to therapy was classified as measurable or
      assessable. RESULTS: The median time to recurrence after first-line therapy was
      10 months (range, 6 to 30). Among 20 measurable and assessable patients, 14 (70%)
      demonstrated a complete clinical response and four (20%) a partial clinical
      response. The response rate with measurable disease was 91% and with assessable
      disease was 89%. The median progression-free interval for all patients was 9.0+
      months (range, 2 to 15). The median progression-free interval for patients with
      measurable or assessable disease was 9.0+ months and for nonassessable disease
      was 7.0+ months. Fifteen patients (60%) have developed recurrence after secondary
      therapy at a median interval of 9.0 months (range, 2 to 15). Only two patients
      have died with a median survival after secondary therapy of 10.0+ months (range,
      2.0 to 21.0+). CONCLUSION: The use of this combination, in this sensitive
      population, has a high response rate and long progression-free interval. In a
      chemotherapy-sensitive population, the activity of alternative second-line agents
      must be interpreted with this perspective.

PMID- 9552058
TI  - High-dose cladribine therapy for chronic myelogenous leukemia in the accelerated
      or blast phase.
AB  - PURPOSE: A phase II clinical trial was performed to evaluate the effectiveness of
      high-dose cladribine (2CDA) for treatment of chronic myelogenous leukemia (CML)
      in the accelerated or blast phase. PATIENTS AND METHODS: Nineteen patients were
      treated. The median age was 55 years (range, 30 to 73). Six were older than 60
      years. Eight had progressed after intensive combination chemotherapy and three
      after allogeneic or autologous transplantation. For the first course, 16 patients
      received 2CDA at 15 mg/m2/d intravenously (i.v.) over 1 hour for 5 days. Two
      received 18 mg/m2 and one received 21.5 mg/m2 daily. The second course was
      escalated to 20 mg/m2/d in five patients. RESULTS: Rapid cytoreduction of
      leukemia occurred in the blood, with the nadir at 10 to 12 days. The median WBC
      count decreased from 36,900/microL before treatment to 500/microL at the nadir
      and recovered to 5,200/microL at day 30. The median platelet count changed from
      113,000/microL to 24,000/microL at the nadir and 71,000/microL at day 30. The
      complete remission (CR) plus partial remission (PR) rate was 47% (95% confidence
      interval [CI], 23% to 72%). One 64-year-old man with lymphoid blast phase of CML
      had a morphologic and cytogenetic CR that lasted 9 months. The median survival
      for all patients was 34 weeks, and the median survival for the eight responders
      was 56 weeks (range, 11 to 167). The median number of days spent in hospital over
      the entire treatment period was 19 (range, 4 to 60). CONCLUSION: High-dose 2CDA
      therapy provides effective palliation for CML in accelerated or blast phases,
      even for heavily pretreated patients.

PMID- 9552059
TI  - Demyelination and single-carbon transfer pathway metabolites during the treatment
      of acute lymphoblastic leukemia: CSF studies.
AB  - PURPOSE: To investigate the hypothesis that methotrexate causes demyelination due
      to a deficiency in S-adenosylmethionine (SAM) during the treatment of acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Twenty-four patients treated
      on the Medical Research Council United Kingdom ALL trial no. 11 (MRC UKALL XI)
      were studied. The trial randomized patients at the presymptomatic CNS treatment
      (PCNS) phase to receive (1) intrathecal methotrexate and cranial radiotherapy
      (CRTX); (2) high-dose intravenous methotrexate with folinic acid rescue and
      continuing intrathecal methotrexate (HDMTX); and (3) continuing intrathecal
      methotrexate alone (ITMTX). Serial CSF samples were collected throughout
      treatment and concentrations of 5-methyltetrahydrofolate (MTF), methionine (MET),
      SAM, and myelin basic protein (MBP) were measured. The results were grouped into
      treatment milestones and compared with an age-matched reference population.
      RESULTS: There was a highly significant effect of both treatment milestones and
      trial arm on the metabolite and MBP concentrations. CSF MTF reached a nadir
      during the induction phase of treatment, while SAM and MET reached their nadir
      during the consolidation phase. CSF MBP mirrored SAM concentration and there was
      a significant inverse relationship between the two. MTF, SAM, and MBP returned to
      normal values by the end of treatment, while MET was increased significantly. The
      effect of treatment was decremental across the ITMTX, HDMTX, and CRTX groups.
      CONCLUSION: Treatment of ALL causes marked abnormalities in the single-carbon
      transfer pathway and subclinical demyelination. Methotrexate is one cause of
      this. Whether these abnormalities contribute to the late cognitive deficits
      requires further study.

PMID- 9552060
TI  - Nucleolar organizer region counts predict complete remission, remission duration,
      and survival in adult acute myelogenous leukemia patients.
AB  - PURPOSE: The analysis of the nucleolar organizer regions (AgNORs) was performed
      in patients with acute myelogenous leukemia (AML) to verify the role of cell
      proliferation in predicting complete remission (CR) and survival. MATERIALS AND
      METHODS: Bone marrow biopsies from 40 adult patients with AML were stained with
      the argyrophilic method. The mean AgNOR number (AgNOR count) was calculated for
      each case. After induction therapy, patients who achieved CR received intensive
      consolidation; two underwent autologous and four allogeneic bone marrow
      transplantations (BMT). RESULTS: The mean AgNOR count for the whole series was
      6.6 (SD = 1.35); it was higher in CR patients than in resistant ones (P = .02).
      The median duration of CR was 26 months for patients with an AgNOR count greater
      than 6.6, but only 6 months for those with lower counts (P = .01). Sixteen
      patients who achieved a CR relapsed and 14 reached a second CR; the median
      duration of second CR was 16 months for patients with AgNOR count greater than
      6.6, but only 5 months for those with lower counts (P = .01). The median survival
      time for the whole series was 14 months, with 30% of patients alive and in
      continuous CR at 103 months. Survival was longer for patients with an AgNOR count
      greater than 6.6 (33 months) than for those with lower counts (6 months; P =
      .0009). In multivariate analysis, when CR was excluded from the model, AgNOR
      count appeared as an independent prognostic variable (P = .005). CONCLUSION:
      AgNOR analysis is a suitable method to assess cell proliferation in bone marrow
      biopsies and can predict CR, remission duration, and survival in AML patients.

PMID- 9552061
TI  - Competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction for
      quantitative assessment of minimal residual disease during postremission therapy
      in acute myeloid leukemia with inversion(16): a pilot study.
AB  - PURPOSE: (1) Quantification of minimal residual disease (MRD) by competitive
      CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction (RT-PCR) in
      patients with acute myeloid leukemia (AML) and inversion(16) [inv(16)] during
      postremission therapy, (2) comparison of this method with conventional two-step
      RT-PCR, and (3) evaluation of a potential prognostic value. PATIENTS AND METHODS:
      MRD of six consecutive adult patients with AML and inv(16)(p13;q22) or
      t(16;16)(p13;q22) who entered complete remission (CR) was monitored by
      competitive CBFbeta/MYH11 RT-PCR in their bone marrow (BM) during postremission
      therapy with high-dose cytarabine (HiDAC) or after BM transplantation with a
      matched unrelated-donor marrow (MUD-BMT) during an observation period of 4.5 to
      27 months after initiation of treatment. RESULTS: Competitive PCR showed a
      gradual decline by at least 4 orders of magnitude after 7 to 9 months in patients
      in continuous CR (CCR), while one patient who relapsed after 13.5 months only
      achieved a reduction by 2 orders of magnitude at the end of consolidation
      therapy. A rapid decrease below the detection limit was observed within 1 month
      in two patients after MUD-BMT. A temporary reappearance of molecular MRD was
      observed in these patients during immunosuppression for graft-versus-host disease
      (GvHD). After reduction of immunosuppression, the level of MRD dropped again
      below the PCR detection limit. Molecular monitoring by conventional two-step RT
      PCR yielded comparable results only when multiple assays per time point were
      performed, while single-assay RT-PCR gave misleading results. CONCLUSION:
      Competitive RT-PCR is a valuable tool for molecular monitoring during
      postremission chemotherapy, as well as after BMT.

PMID- 9552062
TI  - Conversion of interferon-induced, long-term cytogenetic remissions in chronic
      myelogenous leukemia to polymerase chain reaction negativity.
AB  - PURPOSE: Interferon alfa (IFN-alpha) induces complete cytogenetic remission in a
      significant minority of patients with chronic myelogenous leukemia (CML). To
      date, use of the polymerase chain reaction (PCR) has suggested that residual
      disease is present in virtually all these individuals at median follow-up
      intervals of approximately 1 year after initial achievement of cytogenetic
      remission. We sought to determine the PCR status of CML patients with very long
      continuous complete cytogenetic remissions on IFN-alpha. PATIENTS AND METHODS:
      Blood and/or bone marrow samples from 18 CML patients maintained in continuous
      cytogenetic remission by IFN-alpha for at least 1 year were studied for residual
      BCR-ABL mRNA by single-step reverse-transcriptase (RT)-PCR methodology, followed
      by detection of the amplification product by the hybridization protection assay
      (HPA). RESULTS: Ten of 18 patients showed RT-PCR negativity for BCR-ABL. The
      median duration of continuous complete cytogenetic remission at the time of
      sample collection for the negative patients was 42 months versus 21 months for
      the patients whose tests remained positive (P = .05). CONCLUSION: Very long-term
      follow-up of IFN-alpha-treated CML patients in continuous complete cytogenetic
      remission is associated with a decrease in the number of BCR-ABL transcripts to a
      level below that detectable by the RT-PCR assay used in this study.

PMID- 9552063
TI  - Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic
      large-cell lymphoma patients.
AB  - PURPOSE: In the last few years, the search for new biologic markers in high-grade
      non-Hodgkin's lymphomas has provided important results. In particular, soluble
      CD30 (sCD30) levels were elevated in most patients with Hodgkin's disease (HD)
      and anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS: From September
      1988 to October 1993, treatment was completed in 70 previously untreated patients
      with ALCL, of whom 38 had the common type (ALCL-CT) and 32 had the Hodgkin's-like
      subtype (ALCL-HL). Serum sCD30 levels were measured at the time of diagnosis and
      after induction polychemotherapy in all patients; in addition, the initial sCD30
      levels were compared with those obtained from 50 stage-matched patients with HD.
      RESULTS: Pretreatment levels of sCD30 were highly elevated in the stage-matched
      group of HD patients compared with healthy controls; median sCD30 levels in
      patients with ALCL-CT and ALCL-HL were 18 and seven times higher, respectively,
      than in patients with HD. The sCD30 level normalized on achievement of complete
      response (CR). The risk of lower relapse-free survival was associated with bulky
      disease, advanced stage, and high pretreatment sCD30 levels; the risk of lower
      overall survival was associated with advanced stage and pretreatment levels of
      sCD30 in both univariate and multivariate analysis. CONCLUSION: The results of
      this study suggest that sCD30 is a specific prognostic indicator of the risk for
      lower complete response rate and relapse-free expectancy for patients with ALCL.

PMID- 9552064
TI  - Comparable engraftment kinetics following peripheral-blood stem-cell infusion
      mobilized with granulocyte colony-stimulating factor with or without
      cyclophosphamide in multiple myeloma.
AB  - PURPOSE: To compare, in the setting of tandem autotransplantations for multiple
      myeloma (MM), two established methods of peripheral-blood stem-cell (PBSC)
      procurement with chemotherapy or hematopoietic growth factor alone. PATIENTS AND
      METHODS: Between June 1994 and July 1995, 44 patients with MM were randomized to
      PBSC mobilization with either granulocyte colony-stimulating factor (G-CSF) 16
      microg/kg (group 1; n = 22) or high-dose cyclophosphamide (HDCTX) 6 g/m2 plus G
      CSF 5 microg/kg (group 2; n = 22). All 44 patients received melphalan 200 mg/m2
      with their first autograft and 32 patients proceeded to a second transplantation.
      RESULTS: Group 2 required a significantly longer time interval for completion of
      PBSC collection than group 1 (median, 22 v 8 days; P = .0001), greater frequency
      of hospitalization (100% v 32%; P = .0001), and increased transfusion of
      platelets (86% v 18%; P = .0001) and packed RBCs (86% v 55%; P = .02). Likewise,
      the incidence of fever and pneumonia/sepsis were higher in group 2 (P = .02 and P
      = .04, respectively). Surprisingly, despite greater CD34 cell quantities infused
      in group 2, median recovery times of granulocytes (both > 500/microL and
      2,500/microL) and platelets (both > 50,000/microL and > 100,000/microL) were
      similar (all P > .7). Posttransplant toxicities were also similar. CONCLUSION:
      Compared with HDCTX plus G-CSF, high-dose G-CSF alone is associated with lower
      morbidity, shorter duration of PBSC mobilization, and comparable hematopoietic
      recovery after transplantation, which should result in significant cost
      reduction. Considering the relatively limited antitumor activity of HDCTX (10%
      with > or = 50% tumor cytoreduction), PBSC mobilization with HDCTX should be
      limited to selected patients with persistent MM despite induction chemotherapy.

PMID- 9552065
TI  - Back-up bone marrow is frequently ineffective in patients with poor peripheral
      blood stem-cell mobilization.
AB  - PURPOSE: To assess hematologic recovery and procedure-related mortality in
      patients who received high-dose therapy with stem-cell support, in whom the
      peripheral-blood stem-cell (PBSC) collection fails (CD34+ cells < 1 x 10(6)/kg).
      The predictive value of granulocyte-monocyte colony-forming cell (GM-CFC)
      measurements and the value of bone marrow obtained after PBSC collection failure
      was assessed. PATIENTS AND METHODS: The study group comprised 324 consecutive
      patients mobilized with granulocyte colony-stimulating factor (G-CSF) and
      cyclophosphamide (273 patients), G-CSF with other chemotherapy (37 patients), and
      G-CSF alone (14 patients). Between one and four aphereses were performed.
      RESULTS: In 51 of 324 patients, there was failure to obtain 1 x 10(6)/kg CD34+
      cells. Twenty-three patients had greater than 1 x 10(5)/kg GM-CFC; 22 patients
      proceeded to high-dose therapy. Neutrophil recovery occurred within 21 days, but
      platelet independence was delayed (> 28 days) in eight patients. Of 28 patients
      with less than 1 x 10(5)/kg GM-CFC, six received high-dose therapy with PBSC
      alone and five had delayed engraftment. Twelve patients with less than 1 x
      10(5)/kg GM-CFC received high-dose therapy supported by bone marrow collected
      after PBSC collection failure. Eleven patients were assessable for engraftment;
      four patients had slow (> 21 days) or delayed (> 28 days) neutrophil recovery and
      eight patients had delayed platelet recovery. In the group of patients who
      received less than 1 x 10(5)/kg GM-CFC, there were five procedure-related deaths.
      CONCLUSION: This study shows that delayed hematologic recovery is frequent if
      less than 1 x 10(6)/kg CD34+ cells are infused after high-dose therapy,
      particularly with GM-CFC less than 1 x 10(5)/kg. The procedure-related mortality
      in this latter group is high. In most patients whose PBSC collection contains
      less than 1 x 10(5)/kg GM-CFC, the use of bone marrow cells does not improve
      engraftment, which suggests that poor PBSC mobilization usually indicates poor
      marrow function.

PMID- 9552066
TI  - High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal
      cancer: is intrathecal chemotherapy necessary?
AB  - PURPOSE: Standard treatments for neoplastic meningitis are only modestly
      effective and are associated with significant morbidity. Isolated reports suggest
      that concurrent systemic and intrathecal (i.t.) therapy may be more effective
      than i.t. therapy alone. We present our experience, which includes CSF and serum
      pharmacokinetic data, on the use of high-dose (HD) intravenous (i.v.)
      methotrexate (MTX) as the sole treatment for neoplastic meningitis. PATIENTS AND
      METHODS: Sixteen patients with solid-tumor neoplastic meningitis received one to
      four courses (mean, 2.3 courses) of HD (8 g/m2 over 4 hours) i.v. MTX and
      leucovorin rescue. Serum and CSF MTX concentrations were measured daily.
      Toxicity, response, and survival were retrospectively compared with a reference
      group of 15 patients treated with standard i.t. MTX during the same time
      interval. RESULTS: Peak methotrexate concentrations ranged from 3.7 to 55
      micromol/L (mean, 17.1 micromol/L) in CSF and 178 to 1,700 micromol/L (mean, 779
      micromol/L) in serum. Cytotoxic CSF and serum MTX concentrations were maintained
      much longer than with i.t. dosing. Toxicity was minimal. Cytologic clearing was
      seen in 81% of patients compared with 60% of patients treated intrathecally (P =
      .3). Median survival in the HD i.v. MTX group was 13.8 months versus 2.3 months
      in the i.t. MTX group (P = .003). CONCLUSION: HD i.v. MTX is easily administered
      and well tolerated. This regimen achieves prolonged cytotoxic serum MTX
      concentrations and CSF concentrations at least comparable to those achieved with
      standard i.t. therapy. Cytologic clearing and survival may be superior in
      patients treated with HD i.v. MTX. Prospective studies and a reconsideration of
      the use of i.t. chemotherapy for patients with neoplastic meningitis are
      warranted.

PMID- 9552067
TI  - Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous
      ondansetron for highly emetogenic cisplatin-based chemotherapy.
AB  - PURPOSE: To compare the antiemetic efficacy of a single dose of an oral
      antiemetic (granisetron 2 mg) with a single dose of an intravenous (i.v.)
      antiemetic (ondansetron 32 mg) given before cisplatin-based chemotherapy.
      PATIENTS AND METHODS: This was a multicenter, randomized, double-blind, parallel
      group study. Patients (N = 1,054) scheduled to receive cisplatin (> or = 60
      mg/m2)-based chemotherapy were randomized to receive either 2 mg of oral
      granisetron tablets 1 hour before chemotherapy (n = 534) or i.v. ondansetron (32
      mg) 30 minutes before chemotherapy (n = 520). The primary efficacy end point was
      total control (no emesis, no nausea, and no use of antiemetic rescue medication)
      over the initial 24 hours after the start of chemotherapy. Dexamethasone or
      methylprednisolone were permitted, but not required, as concomitant prophylactic
      antiemetics. RESULTS: Total control was equivalent 24 hours after cisplatin
      chemotherapy for single-dose oral granisetron (54.7%) and i.v. ondansetron
      (58.3%) (95% confidence interval [CI], -9.6 to 2.4). Similar proportions of
      patients remained nausea-free in the granisetron group (55.4%) and the
      ondansetron group (59%) (95% CI, -9.6 to 2.4). The rate of complete control of
      emesis was 61.2% in the granisetron group and 67.1% in the ondansetron group (95%
      CI, -11.7 to -0.1). Both treatment regimens were well tolerated, with similar
      patterns of adverse reactions, generally of a mild degree. The most common side
      effects included constipation (14%), headache (15%), and diarrhea (10%).
      CONCLUSION: Oral granisetron, administered as a single 2-mg dose, provided
      equivalent total antiemetic control when compared with i.v. ondansetron (32 mg)
      in patients who received highly emetogenic, cisplatin-based chemotherapy.

PMID- 9552068
TI  - Palliation of pain associated with metastatic bone cancer using samarium-153
      lexidronam: a double-blind placebo-controlled clinical trial.
AB  - PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm)
      lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND
      METHODS: Patients with painful bone metastases secondary to a variety of primary
      malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or
      placebo. Treatment was unblinded for patients who did not respond by week 4, with
      those who had received placebo eligible to receive 1.0 mCi/kg of active drug in
      an open-label manner. Patient and physician evaluations were used to assess pain
      relief, as was concurrent change in opioid analgesia. RESULTS: One hundred
      eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg
      of active drug had significant reductions in pain during each of the first 4
      weeks in both patient-rated and physician-rated evaluations. Pain relief was
      observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first
      4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of
      pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg,
      of active drug. A significant correlation (P = .01) was observed between
      reductions in opioid analgesic use and pain scores only for those patients who
      received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible,
      and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg
      of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain
      relief was observed within 1 week of administration and persisted until at least
      week 16 in the majority of patients who responded.

PMID- 9552069
TI  - Comorbidity and functional status are independent in older cancer patients.
AB  - PURPOSE: Comorbidity is a frequent and often therapeutically limiting problem in
      older cancer patients. However, to date, there is no standard measure of the
      comorbidity burden available for these patients. We tested the performance of two
      comorbidity scales and their relationship with functional status. PATIENTS AND
      METHODS: The Cumulative Illness Rating Scale-Geriatric (CIRS-G) was compared with
      the Charlson scale in 203 patients who received a comprehensive geriatric
      assessment (CGA) in our Senior Adult Oncology Program (SAOP). Study end points
      were variability, reliability, correlation with Eastern Cooperative Oncology
      Group (ECOG) performance status (PS), Activities of Daily Living (ADL), and
      Instrumental Activities of Daily Living (IADL). The relative weight of
      comorbidity versus tumor stage in the correlations with functional status was
      assessed. RESULTS: Median age was 75 years (range, 63 to 91). Sixty-four percent
      of patients scored 0 on the Charlson scale versus 6% on the CIRS-G. The
      correlation between the Charlson and CIRS-G was fair (p = 0.25 to 0.39). CIRS-G
      grade 3/4 had a fair correlation with ADL (p = 0.27). Otherwise, there was low or
      no correlation between comorbidity and functional status across the measures.
      Tumor stage was not correlated with functional status either. Correlation of ECOG
      PS with ADL (p = 0.51)c and IADL (p = 0.61) was moderate. Interrater and test
      retest correlations were good or very good for both the Charlson and CIRS-G.
      CONCLUSION: Comorbidity needs to be assessed independently from functional
      status. Both the Charlson and CIRS-G scales are reliable tools for use in trials
      of older cancer patients. Both can be tested in further studies as predictors of
      outcomes such as toxicity of treatment, changes in functional status, or
      survival.

PMID- 9552070
TI  - Quality of life and cancer pain: satisfaction and side effects with transdermal
      fentanyl versus oral morphine.
AB  - PURPOSE: To compare pain-related treatment satisfaction, patient-perceived side
      effects, functioning, and well-being in patients with advanced cancer who were
      receiving either transdermal fentanyl (Duragesic, Janssen Pharmaceuticals,
      Titusville, NJ) or sustained-release oral forms of morphine (MS Contin, Perdue
      Frederick Co, Norwalk, CT, or Oramorph SR, Roxanne Laboratories, Columbus, OH).
      PATIENTS AND METHODS: A total of 504 assessable cancer patients participated in
      this cross-sectional, quality-of-life study. Relevant elements of four validated
      scales were used--the Functional Assessment of Cancer Therapy-General (FACT-G)
      scale, the Brief Pain Inventory (BPI), the Medical Outcomes Study (MOS)
      questionnaire, and the Memorial Symptom Assessment Scale (MSAS)--as well as
      original scales that were developed and validated for this study. RESULTS: The
      majority of patients in both treatment groups had late-stage (IV/D) cancer.
      Patients who received transdermal fentanyl were more satisfied overall with their
      pain medication than those who received sustained-release oral forms of morphine
      (P = .035). Fentanyl patients also experienced a significantly lower frequency (P
      < .002) and impact (P < .001) of pain medication side effects. These results
      occurred despite the fact that cancer patients who received fentanyl were
      significantly older (P < .001) and had significantly lower functioning and well
      being scores (P = .001). Measures of pain intensity, sleep adequacy, and symptoms
      demonstrated no significant differences between treatment groups. CONCLUSION:
      These data suggest that patients are more satisfied with transdermal fentanyl
      compared with sustained-release oral forms of morphine. A lower frequency and
      reduced impact of side effects with transdermal fentanyl may be one reason cancer
      patients who receive fentanyl are more satisfied with their pain management.

PMID- 9552071
TI  - Oncologists' recognition of depression in their patients with cancer.
AB  - PURPOSE: This study was performed as part of a large depression screening project
      in cancer patients to determine the degree of physician recognition of levels of
      depressive symptoms in cancer patients and to describe patient characteristics
      that influence the accuracy of physician perception of depressive symptoms.
      METHODS: Twenty-five ambulatory oncology clinics affiliated with Community Cancer
      Care, Inc of Indiana enrolled and surveyed 1,109 subjects treated by 12
      oncologists. Subjects completed the Zung Self-Rating Depression Scale (ZSDS) and
      physicians were asked to rate their patients' level of depressive symptoms,
      anxiety, and pain using numerical rating scales. Subjects' sex, age, primary
      tumor type, medications, primary caregiver, and disease stage at diagnosis were
      also recorded. RESULTS: Physician ratings of depression were significantly
      associated with their patients' levels of endorsement of depressive symptoms on
      the ZSDS. However, agreement between physicians and patients is most frequently
      clustered when patients report little or no depressive symptoms. While physician
      ratings are concordant with patient endorsement of no significant depressive
      symptomatology 79% of the time, they are only concordant 33% and 13% of the time
      in the mild-to-moderate/severe ranges, respectively. Physician ratings were most
      influenced by patient endorsement of frequent and obvious mood symptoms, ie,
      sadness, crying, and irritability. Physician ratings also appeared to be
      influenced by medical correlates of patients' level of depressive symptoms
      (functional status, stage of disease, and site of tumor). Additionally, patients
      whose depression was inaccurately classified reported significantly higher levels
      of pain and had higher levels of disability. Physicians' ratings of depression
      were most highly correlated with physicians' ratings of patients' anxiety and
      pain. CONCLUSION: Physicians' perceptions of depressive symptoms in their
      patients are correlated with patient's ratings, but there is a marked tendency to
      underestimate the level of depressive symptoms in patients who are more
      depressed. They are most influenced by symptoms such as crying and depressed
      mood, and medical factors that are useful, but not the most reliable, indicators
      of depression in this population. Physicians' ratings of their patients' distress
      symptoms seem to be global in nature--they are highly correlated with anxiety,
      pain, and global dysfunction. Physician assessment might be improved if they were
      instructed to assess and probe for the more reliable cognitive symptoms such as
      anhedonia, guilt, suicidal thinking, and hopelessness. Screening instruments and
      the use of brief follow-up interviews would help to identify patients who are
      depressed.

PMID- 9552072
TI  - Role of adjuvant chemotherapy in the treatment of invasive carcinoma of the
      urinary bladder.
AB  - PURPOSE: The standard treatment for patients with muscle-invasive carcinoma of
      the urinary bladder is radical cystectomy. While radical cystectomy cures many
      patients with this tumor, almost 50% of them will develop metastatic disease.
      Adjuvant chemotherapy has been proposed for these patients in an attempt to
      reduce the probability of relapse and to improve survival. To assess whether
      adjuvant chemotherapy does benefit patients with muscle-invasive bladder cancer,
      we reviewed all phase II and III studies published in the English literature over
      the last 20 years. METHODS: A review of all published reports was facilitated by
      the use of Medline computer search and by manual search of the Index Medicus.
      RESULTS: Several comparative, nonrandomized studies have indicated that adjuvant
      chemotherapy may prolong disease-free survival. Four randomized studies have been
      conducted and all had a suboptimal patient accrual. Three studies used a
      cisplatin-containing combination chemotherapy and included primarily patients
      with non-organ-confined transitional-cell carcinoma (TCC) of the bladder. All
      three studies indicated that adjuvant chemotherapy improved disease-free survival
      and two of them also showed improvement in event-free survival and overall
      survival, respectively. CONCLUSION: Published series have been unable to
      establish an undisputed benefit of adjuvant chemotherapy over radical cystectomy
      alone for muscle-invasive bladder cancer. The interpretation of the available
      data is compromised by several methodologic and statistical problems. Thus,
      adjuvant chemotherapy cannot be considered as a standard treatment for all
      patients with muscle-invasive carcinoma of the bladder. Well-designed prospective
      randomized studies are needed to clarify the role of adjuvant chemotherapy in
      this disease. However, outside a protocol setting, there is some evidence that
      patients with extravesical disease or with lymph node involvement may benefit
      from adjuvant treatment with cisplatin-based combination chemotherapy. No data
      support such an approach for patients with muscle-invasive but organ-confined
      bladder cancer.

PMID- 9552073
TI  - Emergency treatment of malignant extradural spinal cord compression: an evidence
      based guideline.
AB  - PURPOSE: To review the literature for malignant extradural spinal cord
      compression (MSCC), produce evidence-based recommendations based on the criteria
      used by the Canadian Task Force on the Periodic Health Examination, and make
      suggestions regarding future research directives. METHODS: A systematic review of
      the literature with explicit study selection and evaluation criteria was
      performed. Primary outcome measure was posttreatment ambulation rate. RESULTS:
      There is good evidence to support the use of high-dose dexamethasone (96 mg/d),
      but inconclusive evidence for the use of moderate-dose steroids (16 mg/d) in
      conjunction with radiotherapy (RT) for the treatment of MSCC. Fair evidence
      exists for not using steroids in patients who are nonparetic and ambulatory
      pretreatment, and to give radiation to patients with subclinical spinal cord
      compression (SCC). The remainder of the recommendations are based on inconclusive
      evidence: RT alone should be the first-line treatment for ambulatory patients
      except when there is spinal instability, bony compression, or paraplegia on
      presentation, in which case surgery should be performed. Either modality can be
      used for paraparetic patients who are nonambulatory. Postoperative RT should be
      considered for tumor in residua. Ambulatory, undiagnosed patients should have
      needle biopsy attempted first. Patients should be aggressively screened and
      educated about SCC. CONCLUSION: In general, there were very few papers of high
      methodologic quality found in the literature. More studies are needed to satisfy
      the validity of many of the clinical decisions that are made today with regard to
      the management of MSCC.

PMID- 9552074
TI  - Case one. Bleomycin cutaneous toxicity.

PMID- 9552075
TI  - Case two. Bleomycin cutaneous toxicity.

PMID- 9552076
TI  - Access to quality cancer care: consensus statement. American Federation of
      Clinical Oncologic Societies.
AB  - In his Presidential address on May 17, 1996, Dr John Glick proposed the formation
      of the American Federation of Clinical Oncologic Societies (AFCOS), a coalition
      of all professional clinical oncology societies. AFCOS was intended to address
      heightened concerns about changes in the health care delivery system and the
      impact that they may have on quality patient care. AFCOS places primary emphasis
      on educating patients, their families, health care providers, payors,
      legislators, regulators, and the general public about what constitutes quality
      care, advocating access to and coverage for such care, including clinical trials,
      and supporting and promoting patient-oriented research. Several meetings of the
      coalition have resulted in the development of a consensus statement on quality
      cancer care, which the Journal of Clinical Oncology is pleased to publish in this
      edition. The consensus statement was the product of collaboration among the
      Federation's nine member societies as well as national patient advocacy groups
      represented by the Cancer Leadership Council.

PMID- 9552077
TI  - Concurrent is the key: combined modality small-cell lung cancer.

PMID- 9552078
TI  - Don't be mis-guided when the data are silent and the editorial misses the mark.

PMID- 9552079
TI  - Timing of thoracic irradiation for limited small-cell lung cancer.

PMID- 9552080
TI  - Peripheral T-cell lymphoma after anti-CD20 antibody therapy.

PMID- 9552081
TI  - Ethics of off-label treatment.

PMID- 9552082
TI  - Approaches to primary care: current realities and future visions.

PMID- 9552083
TI  - A four-year randomized controlled trial of hormone replacement and
      bisphosphonate, alone or in combination, in women with postmenopausal
      osteoporosis.
AB  - PURPOSE: Hormone replacement therapy (HRT) with estrogen and treatment with
      bisphosphonates have been shown to increase bone mineral density (BMD) in
      postmenopausal women. This 4-year prospective randomized study was carried out to
      assess the effectiveness of the combined HRT plus etidronate on BMD in
      postmenopausal women with established osteoporosis. PATIENTS AND METHODS: Seventy
      two postmenopausal women (mean age 64.9+/-0.5 years) attending metabolic bone
      disease outpatient clinics with established osteoporosis were randomly allocated
      into one of four treatment groups and monitored for 4 years. All patients
      enrolled in this study including the control group (n=18) received 1.0 g
      elemental calcium and 400 units vitamin D per day. The HRT group (n=18) received
      cyclical estrogen and progesterone; the etidronate group (n=17) received
      intermittent cyclical etidronate; and the combined therapy group (n=19) received
      both HRT and etidronate. BMD was measured in the lumbar spine and the hip before
      treatment and at 2 and 4 years after treatment. Changes in height were recorded,
      and the occurrence of new vertebral fractures were documented in comparison with
      the baseline radiographic evaluation. In 40 patients (10 patients per group),
      analysis of bone histomorphometry was carried out after 4 years of treatment.
      RESULTS: In patients who received the combined therapy, BMD increased in the
      lumbar spine by 10.4% (P <0.001) and in the hip by 7.0% (P <0.001) at 4 years.
      For patients treated with ICE, these increases were 7.3% (P <0.001) and 0.9% (P
      <0.05), and with HRT, the increases were 7.0% (P <0.001) and 4.8% (P <0.01) in
      the vertebrae and femora, respectively. The group treated with calcium and
      vitamin D lost 2.5% (P <0.05) and 4.4% (P <0.01) of BMD in the vertebrae and
      femora, respectively, after 4 years. Patients who received combined therapy had
      significantly higher BMD in both the vertebrae and in the femora (P <0.05) in
      comparison with patients who were treated with HRT or etidronate alone after 4
      years. In comparison with patients in the control group, there was a trend toward
      a lower rate of new vertebral fractures in the treatment groups. Height loss was
      significantly less in all three active treatment groups (HRT [P <0.001],
      etidronate [P <0.02], and combined therapy group [P <0.0001]), in comparison with
      the control group. The combined therapy group did not have a significant height
      loss, in comparison with the HRT (P <0.02) and the etidronate (P <0.001) groups.
      None of the patients had histomorphometric evidence of osteomalacia. CONCLUSION:
      This 4-year randomized study showed an additive effect of etidronate and HRT on
      hip and spine BMD in postmenopausal women with established osteoporosis.

PMID- 9552084
TI  - A randomized, double-blind, placebo-controlled study of growth hormone in the
      treatment of fibromyalgia.
AB  - PURPOSE: The cause of fibromyalgia (FM) is not known. Low levels of insulin-like
      growth factor 1 (IGF-1), a surrogate marker for low growth hormone (GH)
      secretion, occur in about one third of patients who have many clinical features
      of growth hormone deficiency, such as diminished energy, dysphoria, impaired
      cognition, poor general health, reduced exercise capacity, muscle weakness, and
      cold intolerance. To determine whether suboptimal growth hormone production could
      be relevant to the symptomatology of fibromyalgia, we assessed the clinical
      effects of treatment with growth hormone. METHODS: Fifty women with fibromyalgia
      and low IGF-1 levels were enrolled in a randomized, placebo-controlled, double
      blind study of 9 months' duration. They gave themselves daily subcutaneous
      injections of growth hormone or placebo. Two outcome measures--the Fibromyalgia
      Impact Questionnaire and the number of fibromyalgia tender points-were evaluated
      at 3-monthly intervals by a blinded investigator. An unblinded investigator
      reviewed the IGF-1 results monthly and adjusted the growth hormone dose to
      achieve an IGF-1 level of about 250 ng/mL. RESULTS: Daily growth hormone
      injections resulted in a prompt and sustained increase in IGF-1 levels. The
      treatment (n=22) group showed a significant improvement over the placebo group
      (n=23) at 9 months in both the Fibromyalgia Impact Questionnaire score (P <0.04)
      and the tender point score (P <0.03). Fifteen subjects in the growth hormone
      group and 6 subjects in the control group experienced a global improvement (P
      <0.02). There was a delayed response to therapy, with most patients experiencing
      improvement at the 6-month mark. After discontinuing growth hormone, patients
      experienced a worsening of symptoms. Carpal tunnel symptoms were more prevalent
      in the growth hormone group (7 versus 1); no other adverse events were more
      common in this group. CONCLUSIONS: Women with fibromyalgia and low IGF-1 levels
      experienced an improvement in their overall symptomatology and number of tender
      points after 9 months of daily growth hormone therapy. This suggests that a
      secondary growth hormone deficiency may be responsible for some of the symptoms
      of fibromyalgia.

PMID- 9552085
TI  - Prognosis of patients with primary systemic amyloidosis who present with dominant
      neuropathy.
AB  - BACKGROUND: Primary systemic amyloidosis is an uncommon disorder associated with
      the desposition of fragments of immunoglobulin light chains in a variety of
      tissues. Some patients present with peripheral neuropathy. The prognosis of these
      patients is not clear. METHODS: We searched the medical records of all patients
      seen at the Mayo Clinic between January 1, 1978 and December 31, 1994 with the
      diagnosis of amyloidosis. Twenty-six patients with sural nerve biopsy-proven
      amyloid neuropathy and a documented monoclonal protein in the serum or urine were
      studied. RESULTS: The most common symptoms that led to the diagnosis of primary
      amyloid neuropathy were paresthesias (81%), muscle weakness (65%), and numbness
      (58%). The median duration of symptoms before diagnosis was 29 months. Symptoms
      of autonomic neuropathy were present at diagnosis in 17 patients (65%). Other
      organs were involved in most patients. The monoclonal light chain protein
      detected was lambda in 18 patients (69%) and kappa in 8 (31%). The neuropathy was
      chronic, debilitating, and showed relentless progression. Twenty-two patients
      (85%) died (median survival 25 months) and 4 patients were alive at a median
      follow-up of 4.5 years. Progressive amyloidosis was the cause of death in most
      patients. Survival was significantly better in the patients with a serum albumin
      level >3 g/dL (median survival 31 months compared with 18 months; P <0.01, log
      rank test). CONCLUSIONS: Patients with primary systemic amyloidosis in whom
      neuropathy is the dominant clinical manifestation often do not receive a
      diagnosis until years after the onset of symptoms. The prognosis is worse than
      previously indicated. Neuropathy does not improve with therapy.

PMID- 9552086
TI  - Predictors of adverse outcome in cancer patients with candidemia.
AB  - BACKGROUND: Many factors, including severity of illness, neutropenia, intravenous
      catheter management, and drug therapy may affect the outcome of candidemia in
      cancer patients. METHODS: The records of all patients at M. D. Anderson Cancer
      Center who developed one or more positive blood cultures for Candida spp between
      January 1, 1988, and December 31, 1992, were retrospectively reviewed. Four
      hundred ninety-one episodes of candidemia were identified, for which 476 had
      complete medical records, which were reviewed in detail. RESULTS: By 3-month
      follow-up, 52% of the patients had died. Neutropenia, higher APACHE III score,
      and visceral dissemination were associated with poor prognosis. Cure rates,
      adjusted for severity of illness, were similar for fluconazole and amphotericin B
      treatment. Exchange of central venous catheters was associated with a modest
      improvement in prognosis. CONCLUSION: Several factors that influence the outcome
      of candidemia in cancer patients have been identified. These factors may be
      relevant for the clinical management of cancer patients with candidemia, and for
      the design of therapeutic trials.

PMID- 9552087
TI  - Comparison of referring and tertiary cancer center physician's diagnoses in
      patients with leukemia.
AB  - PURPOSE: To analyze the rates of concordance in the diagnosis of various
      hematological malignancies among patients referred to a tertiary cancer center,
      comparing the referring diagnosis with the final diagnosis at the M.D. Anderson
      Cancer Center. PATIENTS AND METHODS: This was a cross-sectional study analyzing
      the 409 patients referred to the M.D. Anderson Leukemia Service in 1995 in whom a
      bone marrow examination was performed by the referring physician and in whom this
      examination was repeated at our institution. We also analyzed 100 cases,
      including 84 of the 409 referred patients for whom the diagnostic outside bone
      marrow slide had been sent for review. RESULTS: The overall concordance rate was
      73%. In 18% discordances were present and considered of major importance
      (affecting treatment and/or prognosis) while in 9% there were minor discordances.
      Major discordance rates were 2% for chronic lymphocytic leukemic leukemia and 5%
      for chronic myelogenous leukemia, but 29% for acute myelogenous leukemia (79
      patients), 43% for acute promyelocytic leukemia (7 patients), 19% for acute
      lymphocytic leukemia (42 patients), 57% for hairy cell leukemia (7 patients), and
      23% for the myelodysplastic syndromes (75 patients). The concordance rate was 76%
      in the 100 cases in which bone marrow specimens permitted comparison of the
      morphologic diagnosis made by M.D. Anderson and the referring physician using the
      same slide, with a rate of 75% in the acute leukemias as finally diagnosed at our
      institution. CONCLUSION: Although in the majority of cases the referring
      physicians and the specialty service agreed on diagnosis, major discordance
      occurs in a significant number of cases, including highly treatable diseases such
      as acute promyelocystic leukemia and hairy cell leukemia.

PMID- 9552088
TI  - The impact of gastroesophageal reflux disease on health-related quality of life.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) affects health-related quality
      of life. METHODS: We enrolled 533 adults with a history of heartburn symptoms for
      at least 6 months of moderate to severe heartburn in 4 of the 7 days before study
      entry. Patients were treated with ranitidine 150 mg twice a day for 6 weeks and
      Gelusil antacid tablets as needed. We measured physician-rated symptoms and the
      Medical Outcomes Study short-form 36 (SF-36) Health Survey at baseline and after
      6 weeks of treatment. Baseline results were compared with normative data for the
      US population and for patients with selected chronic diseases. Treatment response
      was defined as no episode of moderate to severe heartburn for 7 days. Statistical
      significance was set at P <0.001. RESULTS: GERD patients reported significantly
      worse scores on all 8 SF-36 scales, physical function and well-being, and
      emotional well-being compared with the general population. Patients with GERD
      reported worse emotional well-being than patients with diabetes or hypertension.
      Treatment responders demonstrated significantly less pain and better physical
      function, social function, vitality, and emotional well-being compared with
      nonresponders. CONCLUSIONS: Patients with GERD experience decrements in health
      related quality of life compared with the general population. The impact of GERD
      is most striking on measures of pain, mental health, and social function.
      Successful treatment for GERD results in improvements in health-related quality
      of life.

PMID- 9552089
TI  - Resolving the conflicts between general and subspecialty medicine: the internist
      as consulting physician-scientist.
AB  - Internal medicine is confronting a conflict between its generalist and specialty
      roles, coupled with a conflict between the needs of academic internal medicine in
      contrast to those of private practice. The historical origins of these conflicts
      are explored. To resolve these conflicts, internal medicine must rediscover the
      common ground shared by the general internist and specialist, academician and
      practitioner. This common ground is best found in the role of internist as
      physician-scientist. In the future, specialists and general internists will need
      to emphasize their roles as consultants. In the process, internal medicine will
      become smaller and more "academic." The benefits of this role for internal
      medicine should be rapidly demonstrated through outcomes based research in order
      to win over skeptical payors, peers, and the public at large.

PMID- 9552090
TI  - Clinical research: assessing the future in a changing environment; summary report
      of conference sponsored by the American Medical Association Council on Scientific
      Affairs, Washington, DC, March 1996.
AB  - Concerns about funding of clinical research underlie all other problems
      identified at the Council on Scientific Affairs conference. Future National
      Institutes of Health (NIH) budgets are likely to be constant at best, and the
      general public expects cost containment to be an ongoing goal; this is
      exacerbated by the impending Medicare Trust Fund crisis. Meanwhile, traditional
      financial support of clinical research in academic medical centers (AMCs) through
      cross-subsidization is imperiled by competitive pressures largely caused by
      managed care. Although managed care organizations (MCOs) are potentially rich
      sources of funding and other resources, and some not-for-profit companies are
      conducting some research, for-profit MCOs have not demonstrated an understanding
      of the importance of clinical research. Young physicians are being discouraged
      from careers as clinical researchers and established investigators are "dropping
      out" because of demands for clinical productivity and competition for research
      grants, loss of patients/research subjects to managed care, perceived lack of
      status and compensation, and overall uncertainty about continued financial
      support. Efforts to assist current and potential clinical investigators are
      discussed in this report. Loss of patients, denial of reimbursement, and
      competition with MCOs and contract research organizations (CROs) have placed AMCs
      under unprecedented pressure. However, research centers located in AMCs have
      allowed investigators to conduct clinical research by providing a "protected
      environment." Furthermore, many AMCs are determined to continue conducting
      clinical research and are addressing related problems. Although the NIH will
      continue to be a major source of funding for clinical research, partnerships
      between various private and public entities provide important opportunities to
      maximize the productivity of all individuals and institutions involved. Potential
      partnerships include MCOs, AMCs, CROs, pharmaceutical companies and other
      industry, the Department of Defense, the Veterans Health Administration, practice
      based physicians, and private foundations and patient support groups.
      "Partnerships in advocacy" for clinical research will be essential. Efforts to
      recruit for-profit MCOs to the clinical research endeavor identified in this
      report include (1) emphasizing issues of interest to them (eg, outcomes
      research); (2) stressing the significance of some research to the marketplace;
      (3) developing criteria to distinguish individual MCOs on the basis of their
      contribution to the public interest; (4) equating money spent on research with
      "R&D dollars" spent in nonmedical business enterprises; and (5) educating
      purchasers of health care (eg, corporate health plan directors) about clinical
      research. Conducting clinical research in all managed care settings requires
      leadership, the understanding and cooperation of physicians and support staff,
      wise use of limited resources (ie, funding only the best research projects),
      sound methodology, and above all, the perception that the research will
      ultimately improve patient care.

PMID- 9552091
TI  - Treatment strategies for atrial fibrillation.
AB  - Atrial fibrillation is the most common arrhythmia observed in clinical practice,
      occurring in 0.4% of the general population and in up to 4% of people greater
      than 60 years old. It is often associated with other cardiovascular disorders,
      such as hypertension, coronary artery disease, or cardiomyopathy. Critical
      evaluation and management of patients with atrial fibrillation requires knowledge
      of etiology, prognosis, and treatment options of this arrhythmia. On initial
      presentation, emergency electrical cardioversion should be performed if the
      patient is hemodynamically unstable. If the patient is stable, initial rate
      control is recommended, using atrioventricular nodal blocking agents. Further
      treatment mainly depends upon the duration of the episode. Patients who are in
      atrial fibrillation <48 hours can be safely cardioverted. Patients who are in
      atrial fibrillation for >48 hours are commonly anticoagulated for 3 to 4 weeks
      before and after cardioversion because of the risk of thromboembolism formation
      in the left atrial appendage. An alternate strategy, which is especially
      attractive when immediate cardioversion is desired, is transesophageal
      echocardiography to exclude left atrial thrombus followed by prompt
      cardioversion. After cardioversion, sinus rhythm can be maintained with class I
      and III drugs, such as flecainide and propafenone or amiodarone and sotalol. New
      treatment options, such as atrial defibrillation, atrioventricular junctional
      ablation, or modification of atrial pacing to prevent atrial fibrillation, are
      currently under investigation. Although atrial fibrillation is so common in
      clinical practice, it still remains difficult to treat. Conversion and
      maintenance to sinus rhythm with antiarrhythmic drug therapy has not shown any
      improvement in mortality, and some patients may benefit more from ventricular
      rate control. This review article discusses different treatment strategies for
      patients with atrial fibrillation.

PMID- 9552092
TI  - New approaches to anti-inflammatory therapy for asthma.
AB  - Currently, corticosteroids are the therapy of choice for the inflammatory
      component of asthma. This class of drug provides powerful anti-inflammatory
      effects in most patients; however, these effects are not specific and in some
      cases may result in serious side effects. Also, many patients have difficulty
      adhering to therapy with inhaled forms of these drugs, which are administered by
      metered-dose inhalers up to several times per day. There are several other
      therapies that provide potential anti-inflammatory effects, but they are of low
      efficacy, with little definitive anti-inflammatory effect. While efforts are
      currently under way to improve corticosteroid therapy, other directions include
      the development of targeted anti-inflammatory agents. For example, the
      leukotrienes, a family of inflammatory mediators that have been shown to enhance
      bronchoconstriction and airway mucus secretion, have been the focus of numerous
      investigations. Specific leukotriene receptor antagonists and synthesis
      inhibitors have been developed and are currently showing promise in clinical
      trials; one leukotriene receptor antagonist (zafirlukast) and one 5-lipoxygenase
      inhibitor (zileuton) were recently approved by the United States Food and Drug
      Administration for the treatment of asthma.

PMID- 9552093
TI  - Liddle's syndrome.

PMID- 9552094
TI  - Depression, palpitations, and unilateral pulsatile tinnitus due to a dopamine
      secreting glomus jugulare tumor.

PMID- 9552095
TI  - Bigger is still better for internal medicine: keeping the family under the tent.

PMID- 9552096
TI  - Back to the future for internal medicine?

PMID- 9552097
TI  - My vocation.

PMID- 9552098
TI  - When housestaff die: musings of a program director.

PMID- 9552099
TI  - Sister Elizabeth Kenny revisited.

PMID- 9552100
TI  - The contribution of job satisfaction to the transition from acute to chronic low
      back pain.
AB  - OBJECTIVE: To determine the extent to which job satisfaction predicts pain,
      psychological distress, and disability 6 months after an initial episode of low
      back pain (LBP). DESIGN: A longitudinal design was used to follow an inception
      cohort experiencing first-episode low back pain with assessment at 2 and 6 months
      after pain onset. SETTING: Urban medical center outpatient orthopedic clinic.
      PATIENTS: The consecutive sample was comprised of 82 men with initial-onset acute
      LBP (T6 or below, daily pain for 6 to 10 weeks). INTERVENTION: Usual orthopedic
      care. MAIN OUTCOME MEASURES: The primary study outcomes were pain (Descriptor
      Differential Scale, Visual Analog Scales); disability (Sickness Impact Profile,
      Quality of Well-Being); and psychological distress (Beck Depression Inventory,
      Hamilton Rating Scale for Depression, Automatic Thoughts Questionnaire);
      predictor variables were orthopedic impairment (Waddell Physical Impairment
      Index) and job satisfaction (Job Descriptive Index, Work APGAR). RESULTS:
      Measures of job satisfaction, pain, disability, and psychological distress at
      baseline and 6 months after pain onset were separately reduced into factors using
      principle components factor analysis. In hierarchical multiple regression
      analyses, baseline job satisfaction significantly predicted variance in outcome
      scores at 6 months after pain onset, beyond the variance explained by control
      factors (demographics; baseline pain, mood, and disability; orthopedic
      impairment). Zero-order correlations between job satisfaction and orthopedic
      impairment were small and nonsignificant, suggesting that these two variables act
      independently in predicting outcome. Although type of work performed (desk work
      or work requiring light, moderate, or heavy lifting) and social position were
      correlated with job satisfaction at baseline, neither contributed to the
      prediction of outcome at 6 months. CONCLUSIONS: Satisfaction with one's job may
      protect against development of chronic pain and disability after acute onset back
      pain and, alternatively, dissatisfaction may heighten risk of chronicity.
      Vocational factors should be considered in the rehabilitation of acute back
      injury.

PMID- 9552101
TI  - Immunizing against depression and anxiety after spinal cord injury.
AB  - OBJECTIVE: To further report on the effectiveness of early psychological
      intervention in reducing anxiety and depressive mood in persons with spinal cord
      injury 2 years after injury. DESIGN: A nonrandomized, longitudinal, controlled
      trial. SETTING, OUTCOME MEASURES, AND INTERVENTION: Twenty-eight spinal cord
      injured persons participated in group cognitive behavior therapy during hospital
      rehabilitation. They were assessed for depressive mood and anxiety before,
      immediately after, and 12 and 24 months after treatment. The intervention group's
      responses on the measures were compared with a control group of 31 spinal cord
      injured persons who only received traditional rehabilitation services during
      their hospitalization. RESULTS: Subjects in the treatment group with high
      depression and anxiety scores before treatment were significantly less depressed
      and reduced their anxiety to a greater extent 2 years after the injury in
      comparison with similar persons in the control group. CONCLUSIONS: Group
      cognitive behavior therapy for spinal cord injured persons who are abnormally
      depressed and anxious appears to reduce depressive mood and anxiety in the short
      and long term.

PMID- 9552102
TI  - The reliability of a self-reported measure of disease, impairment, and function
      in persons with spinal cord dysfunction.
AB  - OBJECTIVE: To develop a self-report instrument that would provide information
      about the different levels of the disablement process, and that (1) was suitable
      for persons with spinal cord disease (SCD), (2) could be completed quickly, (3)
      could be mailed, (4) had acceptable reliability, and (5) would be clinically
      useful. STUDY DESIGN: Test-retest using a convenience sample. METHODS: Review of
      the literature and an expert panel were used to develop the instrument. It was
      mailed to 49,458 individuals in June 1995 and a second mailing was done in August
      1995. A subset of 725 individuals who responded to both mailings was used to
      examine the instrument's test-retest reliability. RESULTS: The instrument has a
      4th grade reading level and has questions on causal disease, disease severity,
      impairment, activities of daily living (including a self-reported version of the
      Functional Independence Measure, the SRFM), and resource utilization. Individual
      item test-retest reliability was high for a mailed questionnaire; all kappa
      coefficients were near or above .60 and most were over .70. Intraclass
      correlation coefficient for the SRFM was .90 and internal consistency
      (Chronbach's alpha) was .96. CONCLUSION: This instrument provides a new, rapid
      way to obtain information relative to the differing levels of the disablement
      process.

PMID- 9552103
TI  - Seat cushion optimization: a comparison of interface pressure and tissue
      stiffness characteristics for spinal cord injured and elderly patients.
AB  - OBJECTIVE: A method for designing tissue deformation minimizing seat surfaces was
      evaluated. Pressure and stiffness criteria were used to optimize surface shape.
      The method's efficacy for patients with spinal cord injuries (SCI) and a
      comparison of cushion performance and interface characteristics with a group of
      30 elderly patients are presented. DESIGN: Repeated measures, prospective study.
      SETTING: University medical center. PATIENTS: SCI (n=12), elderly (age 65 +
      years) [n=30]. INTERVENTIONS: One flat and two custom foam seat cushions. MAIN
      OUTCOME MEASURES: Interface pressure measured using a pressure sensing pad;
      tissue stiffness and pressure recorded on a rigid programmable seat surface.
      RESULTS: Pressure distributions on contoured cushions for the SCI group contained
      lower values than distributions on flat cushions. A comparison of the pressure
      data between the elderly and SCI showed that significant differences exist
      between interface characteristics. The SCI group had higher peak interface
      pressures for all cushions tested. Tissue stiffness measurements were similar for
      each group. CONCLUSIONS: Results showed improved effectiveness of custom
      contoured foam seat cushions versus flat foam cushions. The results suggest that
      pressure distributions for SCI are more sensitive to support cushion
      characteristics than for the elderly. Further research is needed to determine the
      extent of the difference between the populations represented by these groups.

PMID- 9552104
TI  - Predictors of health status and life satisfaction in spinal cord injury.
AB  - OBJECTIVE: To analyze relationships between injury-related variables, demographic
      variables, functional health status, and life satisfaction of people with spinal
      cord injury (SCI). DESIGN: Cross-sectional survey. SETTING: A community in the
      Netherlands. SUBJECTS: Three hundred eighteen people with SCI, aged 18 to 65
      years. Mean age was 39.4 years and mean time after injury was 3.6 years. MAIN
      OUTCOME MEASURES: Health status was measured with the SIP68. Its six scales were
      aggregated to three dimensions, measuring physical, psychologic, and social
      functioning. Life satisfaction was measured with the Life Satisfaction
      Questionnaire. Data were analyzed by path analysis using LISREL V8. RESULTS:
      Obtained scores showed that respondents suffered from serious limitations in
      physical functioning and social functioning, had only a few limitations in
      psychologic functioning, and were satisfied with their lives in general and with
      most life domains. Physical functioning was accurately predicted by injury
      related variables, but psychologic functioning was not. Next to level and
      completeness of the injury, the number of secondary complications turned out to
      be a predictor of functional health. In a path model that had a close fit with
      the data, injury-related variables were related to health status but not to life
      satisfaction. Social functioning (-.48), marital status (-.38), psychologic
      functioning (-.19), and age (-.16) were significant predictors of life
      satisfaction (total R2=.44). CONCLUSIONS: This study points out the high
      prevalence of secondary complications and their importance to the health status
      of people with SCI. Level of social and psychologic functioning are more
      important predictors of life satisfaction than the seriousness of the injury.

PMID- 9552105
TI  - Catecholamine assays in a rat model for autonomic dysreflexia.
AB  - OBJECTIVE: To determine if norepinephrine (NE) levels increased during autonomic
      dysreflexia (AD) hypertension in spinal cord injured rats. DESIGN: Prospective,
      randomized study of three groups of eight rats that underwent C8 spinal cord
      transection. Two days postoperatively, catecholamine samples were collected from
      the animals as follows: group 1 without preoperative chemical sympathectomy using
      6-hydroxydopamine (6-OH DA) or induced AD; group 2 with induced AD; and group 3,
      preoperative chemical sympathectomy with 6-OH DA and induced AD. SETTING: Basic
      science research laboratory in an academic institution. PARTICIPANTS: Sprague
      Dawley male rats weighing 300g. INTERVENTION: Three episodes of induced AD
      hypertension with bowel distension for 1 minute. RESULTS: Results showed a
      significant difference between groups 1 and 2, 2 and 3, and 1 and 3 (p=.0002,
      ANOVA, Y1/2, post hoc Tukey). The mean NE levels in groups 1, 2, and 3 were 465+/
      400 ng/mL, 1,328+/-1,116 ng/mL, and 31+/-61 ng/mL, respectively. CONCLUSION: NE
      increased during AD in the spinal cord injured rat. NE levels were effectively
      blocked by 6-OH DA when AD was induced. Knowledge of catecholamine levels in this
      process may assist in determining both pathophysiology and potential
      pharmacologic treatment options in future human studies.

PMID- 9552106
TI  - Functional status in limb deficiency: development of an outcome measure for
      preschool children.
AB  - OBJECTIVE: To develop an outcome measure of functional status in preschool
      children with limb deficiency. DESIGN: Parents of preschool children with limb
      deficiency completed self-report measures during a routine medical clinic visit.
      SETTING: Outpatient pediatric clinic. PARTICIPANTS: Fifty-two parents of children
      (ages 4 to 7) with acquired or congenital limb deficiency. MAIN OUTCOME MEASURE:
      The newly developed Child Amputee Prosthetics Project-Functional Status Inventory
      for Preschool children (CAPP-FSIP). RESULTS: Initial psychometric studies
      indicate high internal consistency reliability of the new instrument. Content
      validity was established through expert clinician review. Initial construct
      validity analyses confirm that the CAPP-FSIP discriminates between children with
      upper and lower deficiency and their prosthesis use for functional activities.
      CONCLUSION: The CAPP-FSIP is a promising new measure for evaluating preschool age
      children with limb deficiency.

PMID- 9552107
TI  - Back and hip extensor fatigability in chronic low back pain patients and
      controls.
AB  - OBJECTIVE: To compare the lumbar paraspinal and gluteus maximus muscle
      fatigability between chronic low back pain patients and healthy controls by using
      electromyographic (EMG) spectral analysis during a maximal isometric endurance
      task. DESIGN: A cross-sectional comparative study between chronic low back pain
      patients and healthy control subjects. SETTING: Physical medicine and
      rehabilitation clinic in Finland. SUBJECTS: Twenty women with nonspecific chronic
      low back pain (longer than 3 months) and 15 healthy controls. INTERVENTION:
      Subjects performed maximal voluntary isometric back extensions (MVC) at 30
      degrees forward flexion in a specially designed measurement unit. A 50% MVC load
      was used in isometric endurance test. OUTCOME MEASURES: Low back pain intensity
      was assessed by using the visual analogue scale and functional disability by the
      Oswestry disability index. Time to endurance was measured. Bipolar surface EMG
      recordings were made over the lumbar paraspinal muscles (L3-L4, L5-S1) and over
      the gluteus maximus muscles. Average EMG (aEMG%), and initial spectral median
      frequency (MFinit) and change over time (MFslope) were computed. RESULTS: Pain
      intensity and functional disability were higher and MVC and time to endurance
      were lower in the chronic low back pain group (p < .05). Similar muscle activity
      levels (aEMG%) and MFinit indicated similar muscle loading in both groups at the
      beginning of the endurance test. EMG spectral decreases (MFslope) indicated that
      lumbar paraspinal muscle fatigability was similar in both groups. In the chronic
      low back pain group, the gluteus maximus fatigued faster than in the control
      group (greater MFslope, p < .05). However, the shorter endurance time indicated
      greater fatigability in the chronic low back pain group in general (p < .05).
      CONCLUSIONS: The chronic low back pain patients were weaker and fatigued faster
      than the healthy controls. The EMG fatigue analysis results suggest that the
      gluteus maximus muscles are more fatigable in chronic low back pain patients than
      in healthy control subjects during a sustained back extension endurance test.

PMID- 9552108
TI  - Environment effect of functional task performance in adults with acquired brain
      injuries: use of the assessment of motor and process skills.
AB  - OBJECTIVE: To examine household task performance in both familiar (home) and
      unfamiliar (clinic) environments in adults with acquired brain injuries. DESIGN:
      The research performed was a comparison study examining the effect of the
      environment on functional task performance. Individuals were evaluated using the
      Assessment of Motor and Process Skills both in their homes and in an unfamiliar
      clinic setting. PARTICIPANTS: Twenty individuals with acquired brain injuries
      living in the community. MAIN OUTCOME MEASURES: The Assessment of Motor and
      Process Skills, an observational, standardized, occupational therapy assessment
      tool, was used to evaluate household task performance. RESULTS: Paired one-tailed
      t tests indicated a significant difference between home and clinic performance
      measures in process ability (t=-4.28, p=.00), but no significant difference in
      motor ability performance measures (t=-1.84, p=.410). Scatter plot analyses
      showed that performance scores of 6 of the 20 subjects differed in a clinically
      meaningful way, and that instrumental activities of daily living motor
      performance scores for 3 of the 20 differed in a clinically meaningful way.
      CONCLUSIONS: Individuals with acquired brain injuries may be influenced by their
      environment when performing household tasks, although further study is necessary
      to determine the extent of the environmental effect.

PMID- 9552109
TI  - Severe complications of reflex sympathetic dystrophy: infection, ulcers, chronic
      edema, dystonia, and myoclonus.
AB  - OBJECTIVE: To determine the prevalence, type of complication, predisposing
      factors, and treatment for severe complications in a population of reflex
      sympathetic dystrophy (RSD) patients. DESIGN: Retrospective analysis of the data
      from RSD patients collected over a 12-year period, to investigate the involvement
      of predisposing factors in an RSD population without severe complications
      compared with an RSD population with severe complications. SETTING: Outpatient
      clinic of a department of surgery of a university hospital. PATIENTS: A total of
      1,006 patients with the diagnosis of RSD established according to prospectively
      defined criteria. MAIN OUTCOME MEASURES: The signs and symptoms of every RSD
      patient who visited the department were prospectively documented in the medical
      history; these data were retrospectively analyzed with special regard to RSD with
      severe complications-infection, ulcers, chronic edema, dystonia, and/or myoclonus
      for prevalence, type of complication, and treatment. RESULTS: Seventy-four RSD
      patients who were mostly young and female developed severe complications. More
      than one complication occurred in 91% of the affected extremities. Severe
      complications developed more frequently in the lower extremity (65%). In patients
      in whom the acute RSD started with a decreased skin temperature of the affected
      extremity, severe complications developed significantly more often than in acute
      RSD patients with a warm skin temperature of the extremity from the onset of the
      disease (p < .001). CONCLUSIONS: It is important to recognize "cold" RSD
      immediately at the onset of the disease because this group of RSD patients has a
      higher risk of developing a severe complication, mostly followed by a severe
      disability that is resistant to therapy.

PMID- 9552110
TI  - Team approaches to treating children with disabilities: a comparison.
AB  - OBJECTIVE: To investigate differences in team functioning between the
      multidisciplinary and transdisciplinary models when treating children with
      disabilities. DESIGN: A crossover trial. SETTING: An outpatient educational and
      rehabilitation program in a rehabilitation institute based at a university
      medical center. PARTICIPANTS: A population-based sample of 19 rehabilitation
      specialists and educators. INTERVENTION: Participants attended four team meetings
      using the multidisciplinary approach and then attended four team meetings using
      the transdisciplinary approach. OUTCOME MEASURES: Behavioral ratings of team
      participation (Transdisciplinary Team Rating Scale) and self-report instruments
      of team development (Team Assessment Questionnaire) and treatment planning and
      goal development (Staff Perception Questionnaire). RESULTS: Results of t tests
      confirmed the hypothesis that there was more team member participation during
      transdisciplinary meetings than during multidisciplinary meetings (p=.027). There
      were no differences in levels of team development (p=.329); however, staff
      members favored the transdisciplinary model for treatment planning and goal
      development (p < .001). CONCLUSION: This study provides evidence of the
      effectiveness of the transdisciplinary model. Further research is now needed to
      investigate outcome variables such as rate of success in attaining treatment
      goals when using this model.

PMID- 9552111
TI  - Tracking control in the nonparetic hand of subjects with stroke.
AB  - OBJECTIVE: To examine in subjects with stroke using their nonparetic side how
      different levels of stimulus-response (S-R) compatibility, which require
      different levels of information processing, affect manual tracking control.
      DESIGN: Descriptive study comparing finger movement tracking performance under S
      R-compatible and S-R-incompatible conditions between subjects with stroke and
      healthy controls. Four two-factor analysis of variance tests with one independent
      factor (group, gender, laterality, or order) and one repeated measures factor
      (position) comprised the data analysis. SETTING: University-based research
      setting. PATIENTS: Forty subjects with chronic stroke: 20 right hemiplegia
      (average age, 65.2+/-2.3 yrs); 20 left hemiplegia (average age, 68.6+/-2.3 yrs).
      Fifty-one healthy controls: 24 using nondominant hand (average age, 68.6+/-2.1
      yrs); 27 using dominant hand (average age, 68.7+/-2.0 yrs). All were right
      handed. MAIN OUTCOME MEASURE: Tracking accuracy index (AI), based on root-mean
      square error normalized to scale of each subject's tracking target. RESULTS: In S
      R-incompatible condition, AI of subjects with stroke was not significantly
      different from controls (F[1, 89]=1.73, p=.19). In S-R-compatible condition, AI
      of control subjects was significantly better than subjects with stroke (F[1,
      89]=14.3, p=.0003). CONCLUSION: Manual tracking is impaired in nonparetic hand of
      subjects with stroke, suggesting that information processing, distinctly separate
      from motor weakness, may be an underestimated problem impairing controlled
      movements in individuals with stroke.

PMID- 9552112
TI  - Reliability assessment of isometric knee extension measurements with a computer
      assisted hand-held dynamometer.
AB  - OBJECTIVE: To assess clinically relevant indexes of measurement error of hand
      held dynamometer measurements using a computer-assisted hand-held dynamometer
      (CAHN-DY). DESIGN: In separate sessions, different physical therapists performed
      repeated measurements of maximal isometric knee extension. SETTING: Four physical
      therapy practices and outpatient departments. PATIENTS: Consecutive samples of 30
      male and 28 female patients aged 13 to 77 years, with isolated orthopedic knee
      disorders participated in this study. MAIN OUTCOME MEASURES: For intrarater and
      interrater applications, the standard error of measurement (SEM) and related 95%
      confidence intervals and minimal detectable changes were assessed. RESULTS: Sixty
      percent of the patients performed within the therapist's upper force limit.
      Variance between sessions performed by the same or different therapists accounted
      for a large percentage of the measurement error (70% to 81%). For single
      measurements, the standard error of measurement was assessed not to exceed 10N x
      m. Minimal detectable changes for different designs varied from 13.8 to 28.2N x
      m. CONCLUSIONS: The CAHN-DY facilitated standardization of test performance in a
      satisfactory manner, resulting in less measurement error compared with simple
      hand-held dynamometry.

PMID- 9552113
TI  - Avascular necrosis of bilateral knees secondary to corticosteroid enemas.
AB  - Avascular necrosis (AVN) is a devastating adverse effect of corticosteroid
      therapy rarely reported in the setting of inflammatory bowel disease. We describe
      a 48-year-old woman with 6 weeks of progressive bilateral knee pain resulting in
      the inability to ambulate. Her symptoms developed suddenly, 9 months after
      treatment with hydrocortisone enemas for ulcerative proctitis. On physical
      examination, the patient had knee tenderness, decreased range of motion, and
      flexion contractures. Magnetic resonance imaging showed multiple bony infarcts in
      bilateral distal femora and proximal tibias, consistent with advanced AVN.
      Initial therapy included pain management, serial casting, gentle flexibility and
      strengthening, and limited mobility training. The rehabilitation efforts led to
      functional improvement. Ultimately, bilateral total knee arthroplasties were
      recommended to treat her advanced AVN. This is the first reported case of AVN
      secondary to hydrocortisone enemas. We review the literature and discuss the
      pathophysiology and management of corticosteroid-induced AVN.

PMID- 9552114
TI  - Jejunostomy tube failure: malnutrition caused by intraluminal antegrade
      jejunostomy tube migration.
AB  - Complications occurring with jejunostomy feeding tubes are common and sometimes
      life-threatening. We describe a case of peristalsis-induced intraluminal
      antegrade migration of a jejunostomy tube's distal end with concomitant
      retrograde movement of the small bowel over the tube, which was first discovered
      at autopsy. This ultimately resulted in the jejunostomy feedings entering the
      distal ileum, therefore bypassing most of the small intestine. Subsequent
      malnutrition was a contributing factor in the death of the patient, who had
      required tube feedings after suffering severe head trauma in a motor vehicle
      accident 29 months earlier. The only nutritional interventions attempted before
      death involved various attempts at controlling diarrhea. We discuss the
      incidence, cause, recognition, and prevention of this rarely reported
      complication of a "functioning" jejunostomy feeding tube.

PMID- 9552115
TI  - Three women with lupus transverse myelitis: case reports and differential
      diagnosis.
AB  - Although the association between transverse myelitis (TM) and systemic lupus
      erythematosus (SLE) has been reported previously, it remains a rare clinical
      condition. Our experience treating three women with lupus TM within a few months
      is presented. In each patient, spinal cord dysfunction was accompanied by
      laboratory or clinical evidence of SLE. Further neurologic manifestations, such
      as optic neuritis, developed in all patients, suggesting other diagnoses,
      including multiple sclerosis (MS), Devic's syndrome, and lupoid sclerosis. The
      outcomes for these three women were severe disability, death, and moderate
      disability, respectively. The severity of outcome did not seem to correlate with
      the timing or intensity of treatment. Physiatrists should be aware of the
      potential for neurologic progression in lupus TM, because patients with this
      condition invariably require rehabilitation.

PMID- 9552116
TI  - Outcome after spontaneous spinal epidural hematoma in children: case report and
      review of the literature.
AB  - OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) is an idiopathic
      accumulation of blood in the vertebral epidural space without identifiable
      predisposing factors. First reported in 1869, the clinical outcome in children
      younger than 18 years old has not been clearly delineated. DESIGN: A
      comprehensive review of the English language literature revealed 26 patients
      younger than 18 years old with reported clinical outcomes. The 27th case is
      presented. RESULTS: Complete neurologic recovery occurred in 14 of 27 (52%)
      patients, partial recovery in 12 of 27 (44%) patients, and death in 1 of 27 (4%)
      patients. CONCLUSION: There is an overall good prognosis for neurologic recovery
      in children who experience SSEH.

PMID- 9552117
TI  - Hemicorporectomy: a case study from a physical therapy perspective.
AB  - Hemicorporectomy, literally translated, means half (hemi), body (corpus), removal
      (ectomy). The procedure is indicated as a last resort measure for patients with
      life-threatening conditions such as advanced pelvic tumors, pelvic osteomyelitis,
      crushing pelvic trauma, or intractable decubiti in the pelvic region. We report a
      case in which this mutilating procedure was performed on a 49-year-old man with
      extensive perineal and sacral sores. Squamous cell carcinoma was detected and
      isolated to the pelvic region. His medical history was significant for paraplegia
      secondary to a gunshot wound in 1966. The literature has documented fewer than 45
      procedures of this radical nature. Few of the case studies specifically address
      the rehabilitation of this patient population and none of the articles researched
      were written from a physical therapy standpoint. Articles that addressed the
      concept of rehabilitation comment only that the course of rehabilitation was
      extensive and prolonged. This report provides an overview of the surgical
      procedures and specifically addresses the physical rehabilitation of this patient
      after his hemicorporectomy from a physical therapy perspective. This patient's
      physical therapy was accomplished over a time span of less than 1 month.

PMID- 9552118
TI  - Neuropsychological deficits after whiplash.

PMID- 9552119
TI  - Magnetotherapy: a new intervention?

PMID- 9552120
TI  - Systemic sclerosis.

PMID- 9552121
TI  - Tai-Chi Chuan.

PMID- 9552122
TI  - Identification and localization of neurohypophysial peptides in the brain of a
      caecilian amphibian, Typhlonectes natans (Amphibia: Gymnophiona).
AB  - The amphibian order Gymnophiona contains more than 150 different species of
      caecilians. The characterization and distribution of neurohypophysial peptides,
      however, has not been described for any member of this order. By using high
      performance liquid chromatography, radioimmunoassay, and mass spectrometry, we
      identified the peptide arginine vasotocin (AVT) in brain and pituitary extracts
      from the caecilian Typhlonectes natans. By using immunocytochemistry, we found
      five populations of AVT-immunoreactive (AVT-ir) cells in the brain of T. natans.
      AVT-ir cell bodies were located in the preoptic area, amygdala pars medialis,
      ventral thalamus, dorsal hypothalamic nucleus, and nucleus of the solitary tract.
      AVT-ir fibers and terminal fields were widespread. We also identified a mesotocin
      like peptide. The distribution of this peptide in the brain of T. natans was more
      restricted than the distribution of AVT. Mesotocin-like-immunoreactive cell
      bodies were located almost exclusively in the preoptic area, with only a few
      other cells located in the amygdala pars medialis. This caecilian species,
      therefore, possesses neurohypophysial peptides that are similar in their
      structure and distribution to the peptides found in anuran and urodele amphibian
      orders.

PMID- 9552123
TI  - Some forebrain connections of the gustatory system in the goldfish Carassius
      auratus visualized by separate DiI application to the hypothalamic inferior lobe
      and the torus lateralis.
AB  - The neuroanatomical connections of the diencephalic torus lateralis and inferior
      lobe of the goldfish (Carassius auratus) were studied by retrograde and
      anterograde labeling with the carbocyanine dye DiI. Both structures have
      afferents originating in the central zone of the dorsal telencephalic area as
      well as in the supracommissural nucleus of the ventral telencephalic area, and in
      the secondary gustatory, tertiary gustatory, and posterior thalamic nuclei. Both
      structures investigated have efferents to the tertiary gustatory and posterior
      thalamic nuclei, as well as to the dorsal hypothalamus (dorsal hypothalamic
      neuropil) and superior reticular formation. The torus lateralis receives
      additional afferents from the secondary general visceral nucleus and, sparsely,
      from the dorsal tegmental nucleus. The inferior lobe receives additional
      afferents from the medial zone of the dorsal telencephalic area, as well as from
      the suprachiasmatic, posterior pretectal, central posterior thalamic, caudal
      preglomerular, two tegmental nuclei (T1 and T2), corpus mamillare, and, sparsely,
      from the cerebellar valvula. The inferior lobe has additional efferents to the
      dorsal and ventral thalamus and subglomerular nucleus. The lateral torus and
      inferior lobe are also mutually interconnected. The lateral torus and inferior
      lobe map topographically onto the vagal-related (intraoral) or onto the facial
      related (extraoral) portions, respectively, of both the secondary and tertiary
      gustatory nuclei. Because the posterior thalamic nucleus is reciprocally
      connected with the lateral torus and inferior lobe and is further known to
      project in turn to the area doralis telencephali, it likely represents a
      quaternary gustatory projection nucleus to the telencephalon in cyprinids.
      Whereas the lateral torus seems to be exclusively involved with gustatory and
      general visceral systems, the inferior lobe has inputs from additional sensory
      (e.g., octavolateralis, visual) systems, and, thus, likely represents a
      multisensory integration center.

PMID- 9552124
TI  - Organisation of the tectorotundal and SP/IPS-rotundal projections in the chick.
AB  - The organisation of the neural projections from the optic tectum and pretectal
      nuclei complex, n. subpretectalis / n. interstitio-pretecto-subpretectalis
      (SP/IPS), to the nucleus rotundus (Rt) in chicks was studied by using retrograde
      tracing techniques. After the injection of fluorescent retrograde tracers,
      rhodamine-conjugated latex microspheres, fluorescein-conjugated latex
      microspheres, True Blue, Fluoro-Gold, or rhodamine B isothiocyanate, into
      different regions of Rt and its middorsal extension, the nucleus triangularis
      (T), the distribution of retrogradely labelled neuronal cell bodies in the tectum
      and pretectal nuclei was assessed. Both the ipsilateral and contralateral
      tectorotundal projections were found to be organised topographically in as much
      as different sublaminas of the stratum griseum centrale (SGC) project in an
      orderly manner to Rt and T. The deepest stratum of SGC overlapping into the
      stratum album centrale projects to T. Deep SGC projects to the dorsal Rt and
      superficial SGC to the ventral Rt. A band running through the centre of Rt
      receives input from the central sublamina of SGC, and the caudal central Rt
      receives input from a deeper sublamina than does the rostral central Rt. The
      SP/IPS projects to the ipsilateral Rt only and the projection order is dorsal SP
      to dorsal Rt, ventral SP to ventral Rt and middle SP to the central band of Rt.
      The neurones in IPS and the nucleus of the tractus tectothalamicus project to T.
      Thus, Rt and T receive topographically both tecto- (excitatory) and SP/IPS-
      (inhibitory) projections. The possible functional implications for parallel
      information processing in these projections are discussed.

PMID- 9552125
TI  - Morphological and electrophysiological characteristics of noncholinergic basal
      forebrain neurons.
AB  - Cholinergic neurons in the basal forebrain are the focus of considerable interest
      because they are severely affected in Alzheimer's disease. However, both
      cholinergic and noncholinergic neurons are intermingled in this region. The goal
      of the present study was to characterize the morphology and in vivo
      electrophysiology of noncholinergic basal forebrain neurons. Neurons in the
      ventral pallidum and substantia innominata were recorded extracellularly, labeled
      juxtacellularly with biocytin and characterized for the presence of choline
      acetyltransferase immunoreactivity. Two types of ventral pallidal cells were
      observed. Type I ventral pallidal neurons had axons that rarely branched near the
      cell body and tended to have smaller somata and lower spontaneous firing rates
      than did type II ventral pallidal neurons, which displayed extensive local axonal
      arborizations. Subtypes of substantia innominata neurons could not be
      distinguished based on axonal morphology. These noncholineregic neurons exhibited
      local axon arborizations along a continuum that varied from no local collaterals
      to quite extensive arbors. Substantia innominata neurons had lower spontaneous
      firing rates, more variable interspike intervals, and different spontaneous
      firing patterns than did type II ventral pallidal neurons and could be
      antidromically activated from cortex or substantia nigra, indicating that they
      were projection neurons. Ventral pallidal neurons resemble, both morphologically
      and electrophysiologically, previously described neurons in the globus pallidus,
      whereas the substantia innominata neurons bore similarities to isodendritic
      neurons of the reticular formation. These results demonstrate the heterogeneous
      nature of noncholinergic neurons in the basal forebrain.

PMID- 9552126
TI  - CalbindinD28k- and parvalbumin-immunoreactive neurons form complementary
      sublaminae in the rat superior colliculus.
AB  - By using light microscopic immunocytochemistry and computer analysis, we have
      mapped the distributions of two calcium-binding proteins (CaBPs), calbindinD28k
      (CB) and parvalbumin (PV), in the rat superior colliculus (SC). The patterns of
      CaBP expression were complementary. A band of heavily labeled, medium-sized CB
      immunoreactive cells (CB-cells) was centered in the optic layer (OL), whereas PV
      immunoreactive cells (PV-cells) were found predominantly in the intermediate gray
      layer (IGL), where they were clustered within patches of PV-labeled fibers. The
      superficial gray layer (SGL) could be divided into two sublaminae. CB-cells were
      found mostly in the dorsal half of the SGL, whereas PV-cells were scattered
      throughout the ventral SGL and the dorsal OL. Most of the CaBP-immunoreactive
      cells in the SGL were small bipolar cells with vertically oriented dendrites;
      however, there were also some PV-cells with horizontally oriented dendrites.
      Quantitative analysis of the CaBP distributions reinforced our observations that
      these cells are distributed in complementary tiers that are not restricted to the
      traditional laminae. The size and shape of some of these tiers were determined
      from a three-dimensional reconstruction of serial sections. The complementarity
      of the CaBP-immunoreactive tiers was also confirmed by fluorescence microscopy of
      double-labeled sections, in which few if any double-labeled neurons were
      observed. Complementary tiers of CB-cells and PV-cells have been observed
      previously in the SC of the cat. The present results demonstrate them in another
      species and further suggest that there are functional sublaminae in the SC that
      can be distinguished by CaBP content.

PMID- 9552127
TI  - Ultrastructural evidence for prominent postsynaptic localization of alpha2C
      adrenergic receptors in catecholaminergic dendrites in the rat nucleus locus
      coeruleus.
AB  - Alpha-2-adrenergic receptor (alpha2-AR) agonists potently inhibit the activity of
      noradrenergic neurons of the locus coeruleus (LC), an effect that may be mediated
      by the A- and/ or C-subtypes of alpha2-AR (alpha2A- and alpha2C-AR). To gain
      insight into the functional significance of these alpha2-AR subtypes in the LC,
      we have examined their ultrastructural localization by using subtype-specific
      antibodies. We recently demonstrated that alpha2A-ARs are localized prominently
      in axon terminals and catecholaminergic dendrites in the LC. In the present
      study, we sought to identify the subcellular substrates underlying alpha2C-AR
      actions in the LC by analyzing the ultrastructural distribution of alpha2C-AR
      immunoreactivity (alpha2C-AR-IR) in sections that were dually labeled for the
      catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Alpha-2C-AR-IR was
      predominantly localized in dendrites, most of which also contained immunolabeling
      for TH. Within such dendrites, alpha2C-AR-IR was associated with the plasma
      membrane and occasionally Golgi cisternae and tubulovesicles. The vast majority
      of dendrites containing alpha2C-AR-IR received asymmetric (excitatory) contacts
      from unlabeled axon terminals that often contained dense core vesicles. Alpha-2C
      AR-IR was observed in some unmyelinated axons and astrocytic processes that were
      apposed to TH-immunoreactive dendrites but was rarely associated with axon
      terminals. These results provide the first ultrastructural evidence that alpha2C
      ARs (1) are localized postsynaptically in catecholaminergic neurons of the LC and
      (2) may be strategically situated to modulate the activation of LC neurons by
      excitatory inputs.

PMID- 9552128
TI  - Neurogenic role of the neural gland in the development of the ascidian, Botryllus
      schlosseri (Tunicata, Urochordata).
AB  - In adult ascidians, the neural complex consists of a cerebral ganglion (the
      brain) and the associated neural gland. We have studied the development of the
      neural complex during the vegetative reproduction of the colonial ascidian
      Botryllus schlosseri, the buds of which arise from the atrial mantle of the
      parental zooid. Each bud develops into a new organism within which a neural
      complex becomes differentiated. We found that the presumptive (pioneer) nerve
      cells that ultimately form the cerebral ganglion of the adult arise as migratory
      cells from a primordial cluster of rudimentary gland cells. Hence, the neural
      gland appears to be neurogenic in that it serves as the cellular source of
      components that differentiate into conventional nerve cells. In the adult, these
      cells take on the form of a typical invertebrate ganglion with an outer cortex of
      nerve cell bodies and an internal medulla. This medulla consists of a neuropile
      of neuronal processes making classical synaptic contacts. The adult neural gland
      differentiates into a structure with a ciliated duct that opens into the
      branchial chamber, the body of the gland, and the dorsal organ, which is quite
      distinct from the dorsal strand of other ascidians. The rudimentary neural gland
      cells, therefore, differentiate into one of two distinct pathways: the first,
      glandular, is possibly involved in the evaluation of environmental signals, and
      the other, nervous, leads to brain formation. This compares with the vertebrate
      situation in which the olfactory-pituitary placodes are thought to originate from
      a common cellular source. Thus, these data support the earlier contention of a
      homology between the tunicate neural gland and the vertebrate adenohypophysis.

PMID- 9552129
TI  - Interleukin-1beta and its type 1 receptor are expressed in developing neural
      circuits in the frog, Xenopus laevis.
AB  - The cytokine interleukin-1 beta (IL-1beta) is an evolutionarily conserved
      molecule that was originally identified in the immune system. In addition to
      regulating peripheral immune responses, IL-1beta plays an important role in
      mediating neural-immune interactions and regulating glial activities during
      healing and repair in the damaged nervous system. Active IL-1beta is produced by
      interleukin-converting enzyme (ICE), a caspase thought to be involved in the
      induction of apoptosis. We report that, in the developing frog, Xenopus laevis,
      IL-1beta and the IL-1 type 1 receptor proteins are coexpressed in specific
      neurons that comprise early sensory-motor circuits. IL-1beta and IL-1 type 1
      receptor proteins are colocalized in specific midbrain and hindbrain reticular
      cells, including Mauthner's neuron; specific cells in the trigeminal (fifth),
      lateral line (seventh), and vestibular (eighth) cranial ganglia; oculomotor
      neurons; and the primordial Purkinje cells of the lateral cerebellar auricle. In
      the spinal cord, Rohon-Beard sensory neurons, dorsal root ganglion cells, and
      primary motoneurons are immunopositive. Anteriorly, the olfactory pits, olfactory
      nerves, and olfactory bulbs are labeled, as are retinal cells, especially
      photoreceptor inner segments. With regard to the function of IL-1beta during
      neural development, IL-1beta and its type 1 receptor are present throughout the
      course of neural development in identifiable, long-lived neurons, such as
      Mauthner's neuron. These and other data suggest that IL-1beta and its type 1
      receptor may be involved in the maintenance of cell survival rather than
      induction of neuronal death.

PMID- 9552130
TI  - Hippocampal interneurons expressing glutamic acid decarboxylase and calcium
      binding proteins decrease with aging in Fischer 344 rats.
AB  - Aging leads to alterations in the function and plasticity of hippocampal
      circuitry in addition to behavioral changes. To identify critical alterations in
      the substrate for inhibitory circuitry as a function of aging, we evaluated the
      numbers of hippocampal interneurons that were positive for glutamic acid
      decarboxylase and those that expressed calcium-binding proteins (parvalbumin,
      calbindin, and calretinin) in young adult (4-5 months old) and aged (23-25 months
      old) male Fischer 344 rats. Both the overall interneuron population and specific
      subpopulations of interneurons demonstrated a commensurate decline in numbers
      throughout the hippocampus with aging. Interneurons positive for glutamic acid
      decarboxylase were significantly depleted in the stratum radiatum of CA1, the
      strata oriens, radiatum and pyramidale of CA3, the dentate molecular layer, and
      the dentate hilus. Parvalbumin interneurons showed significant reductions in the
      strata oriens and pyramidale of CA1, the stratum pyramidale of CA3, and the
      dentate hilus. The reductions in calbindin interneurons were more pronounced than
      other calcium-binding protein-positive interneurons and were highly significant
      in the strata oriens and radiatum of both CA1 and CA3 subfields and in the
      dentate hilus. Calretinin interneurons were decreased significantly in the strata
      oriens and radiatum of CA3, in the dentate granule cell and molecular layers, and
      in the dentate hilus. However, the relative ratio of parvalbumin-, calbindin-,
      and calretinin-positive interneurons compared with glutamic acid decarboxylase
      positive interneurons remained constant with aging, suggesting actual loss of
      interneurons expressing calcium-binding proteins with age. This loss contrasts
      with the reported preservation of pyramidal neurons with aging in the
      hippocampus. Functional decreases in inhibitory drive throughout the hippocampus
      may occur due to this loss, particularly alterations in the processing of feed
      forward information through the hippocampus. In addition, such a profound
      alteration in interneuron number will likely alter inhibitory control of
      excitability and neuronal synchrony with behavioral states.

PMID- 9552131
TI  - The Shwachman Award of the North American Society for Pediatric Gastroenterology
      and Nutrition presentation.

PMID- 9552132
TI  - Primary eosinophilic esophagitis in children: successful treatment with oral
      corticosteroids.
AB  - BACKGROUND: The histologic appearance of esophageal eosinophils has been
      correlated with esophagitis and gastroesophageal reflux disease in children.
      Esophageal eosinophilia that persists despite traditional antireflux therapy may
      not represent treatment failure, but instead may portray early eosinophilic
      gastroenteritis or allergic esophagitis. In this study, a series of pediatric
      patients with severe esophageal eosinophilia who were unresponsive to aggressive
      antireflux therapy were examined and their clinical and histologic response to
      oral corticosteroid therapy assessed. METHODS: Of 1809 patients evaluated
      prospectively over 2.5 years for symptoms of gastroesophageal reflux, 20 had
      persistent symptoms and esophageal eosinophilia, despite aggressive therapy with
      omeprazole and cisapride. These patients were treated with 1.5 mg/kg oral
      methylprednisolone per day, divided into twice-daily doses for 4 weeks. All
      patients underwent clinical, laboratory, and histologic evaluation before and
      after treatment. RESULTS: Histologic findings in examination of specimens
      obtained in pretreatment esophageal biopsies in children with primary
      eosinophilic esophagitis indicated significantly greater eosinophilia (34.2+/-9.6
      eosinophils/high-power field [HPF]) compared with that in children with
      gastroesophageal reflux disease who responded to medical therapy (2.26+/-1.16
      eosinophils/HPF; p < 0.001). After corticosteroid therapy, all but one patient
      with primary eosinophilic esophagitis had dramatic clinical improvement,
      supported by histologic examination (1.5 +/-0.9 eosinophils/HPF, p < 0.0001).
      CONCLUSIONS: Pediatric patients in a series with marked esophageal eosinophilia
      and chronic symptoms of gastroesophageal reflux disease unresponsive to
      aggressive medical antire-flux therapy had both clinical and histologic
      improvement after oral corticosteroid therapy.

PMID- 9552133
TI  - Antineutrophil cytoplasmic antibody subtypes in children and adolescents after
      ileal pouch-anal anastomosis for ulcerative colitis.
AB  - BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies occur frequently in
      adult patients with chronic pouchitis after colectomy and ileal pouch-anal
      anastomosis for ulcerative colitis. The purpose of the study was to determine the
      prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic
      antineutrophil cytoplasmic antibody in children and adolescents who undergo
      colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial
      adenomatous polyposis. METHODS: Five groups of children and adolescents (age, <20
      years) were studied, with the following histories: acute pouchitis and history of
      ulcerative colitis; chronic pouchitis and history of ulcerative colitis;
      pouchitis with Crohn's disease features and a history of ulcerative colitis; no
      pouchitis and a history of ulcerative colitis; and familial adenomatous
      polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels
      and titers were detected in postoperative sera by enzyme-linked immunosorbent
      assay, and positive results were subtyped by indirect immunofluorescence.
      RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies and
      cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of
      ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with
      familial adenomatous polyposis (p < 0.001). There was no significant correlation
      between the frequency of perinuclear antineutrophil cytoplasmic antibodies and
      ulcerative colitis patient subgroups (patients with and without pouchitis, 66%
      and 75%). Similarly, there was no significant correlation between the frequency
      of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis
      patient subgroups (patients with and without pouchitis, 19% and 8%). The
      frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with
      Crohn's disease features (50%), was increased, but this difference was not
      significant. CONCLUSIONS: There is a high frequency of perinuclear antineutrophil
      cytoplasmic antibodies in children and adolescents who undergo ileal pouch-anal
      anastomosis for ulcerative colitis, whether or not they have pouchitis. The
      frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this
      patient population. Additional studies will be required to determine whether the
      presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with
      the postoperative development of features of Crohn's disease.

PMID- 9552134
TI  - Helicobacter pylori infection, gastric acid secretion, and infant growth.
AB  - BACKGROUND: Helicobacter pylori infection is very common in Gambian infants and
      children, who are also at risk of chronic diarrhoea and undernutrition. Acute H.
      pylori infection is associated with depressed gastric acid secretion, and loss of
      the gastric acid barrier may predispose to enteric infections. METHODS: In a
      prospective study a noninvasive test of gastric acid output (measurement of
      change in urine acid output before and after a feed) was performed on a
      population of Gambian infants at high risk of H. pylori infection. The 13C urea
      breath tests was used to measure the prevalence of H. pylori infection and growth
      was measured by serial anthropometry. RESULTS: In 101 infants aged 3 to 12
      months, there was a significant relation between H. pylori infection and
      depressed urine acid output in those aged 6 months, during weaning when growth
      failure and malnutrition begin. Those infants with sustained H. pylori infection
      grew less well than those without. CONCLUSIONS: We speculate that H. pylori,
      acquired in infancy, could be a "key that opens the door" to enteric infection in
      childhood, leading to recurrent diarrhoea, malnutrition, and growth failure.

PMID- 9552135
TI  - Persistent hepatitis G virus infection after neonatal transfusion.
AB  - BACKGROUND: Recently two Flaviviridae-like viruses have been discovered and named
      GB virus C and hepatitis G virus. Molecular characterization showed them to be
      different subtypes of the same virus. An association with posttransfusion
      hepatitis and with sporadic and fulminant hepatitis was reported, but most
      infected people remain asymptomatic. Data concerning hepatitis G virus infection
      in infants and children have not been reported to date. The prevalence of
      hepatitis G virus infection in children after transfusion of blood products in
      the neonatal period was studied. METHODS: Serum samples from 251 children, who
      had received blood products in the first 4 weeks of life and who had been
      reexamined as part of another study at a mean interval of 37 months (range, 10
      70) after last transfusion, were analyzed for hepatitis G virus infection. Follow
      up examinations were performed in 14 of 19 hepatitis G virus-positive children 12
      to 17 years after the last transfusion. Presence of hepatitis G virus RNA in
      serum was determined by a reverse transcription polymerase chain reaction assay
      with nested primers from the helicase region of the hepatitis G virus. To prove
      specificity of the hepatitis G virus, reverse transcription polymerase chain
      reaction assay and compare follow-ups with initial sequences, direct sequencing
      of the NS3 and NS5 regions of the hepatitis G virus was performed. RESULTS:
      Hepatitis G virus RNA was detected in 19 of 251 patients (7.6%); sequence
      analysis showed the isolates to be of hepatitis G virus type. None of the
      patients with hepatitis G virus infection had evidence of liver disease, although
      3 patients were coinfected with hepatitis C virus. Four of 14 patients who were
      reinvestigated after a mean of 15 years showed persistent hepatitis G virus
      infection. Each of the 4 children was healthy. In none were clinical signs of
      liver disease observed; liver function test results were within the normal range.
      CONCLUSIONS: Children receiving blood transfusions in the neonatal period are at
      increased risk of hepatitis G virus infection with a high rate of chronic
      infection. However, as in the findings in several studies of adult transfusion
      recipients, in the current results, no association between hepatitis G virus
      infection and clinical or biochemical signs of hepatitis or extrahepatic disease
      could be seen.

PMID- 9552136
TI  - Lipid digestion in cystic fibrosis: comparison of conventional and high-lipase
      enzyme therapy using the mixed-triglyceride breath test.
AB  - BACKGROUND: Fat maldigestion occurs in most patients with cystic fibrosis.
      Conventional pancreatic enzyme replacement therapy partially corrects this
      defect. In this study, the mixed-triglyceride breath test was used to evaluate
      whether high-lipase enzymes are equivalent to conventional enzymes in improving
      fat maldigestion in children with cystic fibrosis. METHODS: Fat digestion was
      studied in 11 patients with a mean age of 10.5 years. The mean intake of
      conventional enzyme capsules a day was 19. Four 13C mixed-triglyceride tests were
      performed on separate days and in random order. One test was taken without enzyme
      substitution, one with three capsules of 8,000 FIP units Creon (pancreatinum,
      Kali-chemie Pharma, Hannover, Germany) and one with one capsule of 25,000 FIP
      units. The fourth test was made with 13C octanoic acid to study gastric emptying
      time. RESULTS: Without enzyme intake, the mean cumulative percentage of 13C dose
      exhaled after 6 hours was 7.2+/-3.7%. This increased to 14.4+/-4% with intake of
      conventional pancreatinum and to 14.3+/-5.1% with intake of high-lipase
      pancreatinum (p = 0.0008 for both; paired t-test). There was no difference
      between both treatments. Also, the time course of 13C exhalation measured by
      percentage of 13CO2 exhaled per hour did not differ between enzyme treatments.
      CONCLUSIONS: The 13C mixed-triglyceride test is noninvasive and documents
      improved lipid digestion with pancreatic enzyme replacement therapy. If the
      lipase dose is kept constant, results obtained with high-lipase preparations are
      equivalent to those obtained with conventional preparations.

PMID- 9552137
TI  - Effect of formula supplemented with docosahexaenoic acid and gamma-linolenic acid
      on fatty acid status and visual acuity in term infants.
AB  - BACKGROUND: Docosahexaenoic acid is present in high concentration in retina and
      does not influence visual development in preterm infants. It is still under
      discussion whether docosahexaenoic acid is important for visual development in
      term infants. METHODS: Thirty-seven infants fed formula for a median of 14 days
      were randomized at median age of 25 days to three formulas: a) DHAGF: 0.3 wt%
      docosahexaenoic acid and 0.5 wt% gamma-linolenic acid; b) DHAF 0.3 wt%
      docosahexaenoic acid; or c) STF: standard formula without long-chain
      polyunsaturated fatty acids and 17 breast-fed infants were observed, using blood
      samples and anthropometric measurements from 1 to 4 months of age. At 4 months,
      visual acuity was measured by swept steady-state visual evoked potential. A cross
      sectional study on 25 breast-fed infants was carried out as a reference group for
      the analyses. RESULTS: Infants fed the two docosahexaenoic acid-supplemented
      formula had relative docosahexaenoic acid concentrations in red blood cell
      phospholipids almost as high as those in breast-fed infants, whereas infants in
      the standard formula group had significantly lower levels. The addition of gamma
      linolenic acid to the formula had a positive effect on red blood cell arachidonic
      acid levels, compared with levels obtained using fish oil only. Visual acuity was
      significantly different among all feeding groups (analysis of variance; p = 0.05,
      means +/- standard deviation: breast-fed, 0.37+/-0.06 logMAR; DHAF and DHAGF
      combined, 0.40+/-0.07 logMAR; and standard formula 0.44+/-0.07 logMAR. However,
      there was no statistical difference among the formula groups. In a multiple
      regression analysis including all formula-fed infants, weight at delivery (p =
      0.002), but not type of formula, was significantly associated with visual acuity
      at 4 months of age. CONCLUSIONS: The addition of docosahexaenoic acid resulted in
      concentrations in red blood cells at similar levels as those in breast-fed
      infants, whereas the increase in visual acuity did not reach significance. The
      addition of gamma-linolenic acid resulted in higher arachidonic acid
      concentrations in red blood cells.

PMID- 9552139
TI  - Functional results of laparoscopic fundoplication in children.
AB  - BACKGROUND: There is no evidence that the results of laparoscopic fundoplication
      in children match those of the open procedure. In the current report, pre- and
      postoperative function of the antireflux barrier is examined in children having
      laparoscopic fundoplication for gastroesophageal reflux. METHODS: Twenty-seven
      patients with gastroesophageal reflux, aged 7.2+/-4.5 years, were operated on for
      unremitting gastrointestinal symptoms (n = 24), with respiratory tract disease (n
      = 11), cystic fibrosis (n = 2), or brain damage (n = 11). Gastrostomy was added
      in 5 cases. Barium contrast study, pH-metering, endoscopic examination, and
      biopsy were performed before and after a median of 19 months (range, 8 to 46)
      after operation. RESULTS: At diagnosis, 15 of 21 patients had esophagitis that
      was moderate or severe in 11 (1 with Barrett's esophagus). Symptoms disappeared
      after fundoplication in all but 2 patients, in whom they became milder. The
      reflux index decreased from 20.2+/-20% to 4.9+/-9% and became normal in all
      except 4 children (2 with brain damage and 1 with cystic fibrosis). Open repair
      of the failed wrap was considered necessary in only 1 of them. CONCLUSIONS:
      Laparoscopic fundoplication is as effective as the open procedure (14% overall
      failure rate). However, the failure rate in neurologic patients (18%) suggests
      that before reaching conclusions on the benefits of this approach, careful long
      term assessment of the functional results is necessary.

PMID- 9552138
TI  - T-cells and HLA-class II expression in the large intestine of infants in the
      early postnatal period.
AB  - BACKGROUND: There is only limited knowledge of the development of the immune
      responses of the gut in very young infants after exposure to bacterial and food
      antigens at birth. METHODS: In this study, 49 large intestinal biopsy specimens,
      which were judged to have normal morphology, were taken from 49 young infants.
      Eleven patients had Hirschsprung's disease (group 1) and 38 had miscellaneous
      conditions (group 2). The densities of T cells, their subsets expressing surface
      antigens CD8 and CD4, and T-cell receptors alpha/beta or gamma/beta were
      measured, as well as densities of mononuclear and epithelial cells expressing HLA
      class II antigens. RESULTS: T-cell densities in groups 1 and 2 were similar.
      Patients with Hirschsprung's disease had significantly more HLA-DR (p = 0.006)
      and HLA-DP-expressing cells (p = 0.003) in the lamina propria than did the
      patients in group 2. In group 1, HLA-DR- (r = 0.58; p = 0.46) and HLA-DP
      expressing cells (r = 0.66; p = 0.03) showed a significant positive regression
      with age in the lamina propria, whereas in group 2, HLA-DR+ cells in the lamina
      propria showed marked (r = -0.9; p = 0.006) negative regression during the first
      1.5 months of life. In contrast to results in previous reports, in the current
      results, HLA-D region antigens were present in the epithelium in a considerable
      proportion (up to one fourth) of specimens from the large intestine in both
      groups. CD3+ (r = -0.59; p = 0.006) and CD4+ (r = -0.64; p = 0.002) cells showed
      a strong negative regression with age in the lamina propria during the first 2.5
      months; and thereafter, there was a weak, insignificant rise in the numbers of
      these cells. The distribution of CD4+, CD8+, and TCR alpha/beta or gamma/beta T
      cells of the epithelium of the young infants did not differ significantly from
      that in the epithelium of adults. CONCLUSIONS: These results show that several
      significant changes occur in the mucosal immune system during the first few weeks
      of life.

PMID- 9552140
TI  - Butyrate and glucose metabolism in isolated colonocytes in the developing rat
      colon.
AB  - BACKGROUND: The newborn colon is devoid of microflora, in that bacterial
      colonization is established after birth. Short chain fatty acids, products of
      bacterial fermentation, are the major energy source for colonocytes. Because it
      is not known whether colonocytes in the newborn can metabolize butyrate, this was
      examined in newborn and infant rat colon. METHODS: Isolated colonocytes from rats
      of different perinatal ages were incubated with 14C-labeled butyrate or glucose
      in vitro. Complete oxidation was estimated by the production of 14C-labeled
      carbon dioxide, whereas intermediate metabolites were measured enzymatically.
      RESULTS: Oxidation of butyrate (in micromoles per hour per milligram of protein)
      was highest in newborns (5.83+/-1.76), declining to 1.32+/-0.28 at day 10 and to
      0.34+/-0.04 in adult rats. Glucose oxidation was also highest at birth (0.39+/
      0.23), with a minor increase at approximately day 20 (weaning period) before
      decreasing to adult levels (0.05+/-0). Butyrate oxidation was substantially
      higher than was glucose oxidation in all age groups. Production of metabolic
      intermediates paralleled substrate oxidation. Acetoacetate production was 4.35+/
      2.68, 2.07+/-1.29, and 0.27+/-0.09 nmol/hr per milligram of protein in newborns,
      at postnatal day 10, and in adults, respectively. The corresponding values for
      beta-hydroxybutyrate were 3.62+/-3.35, 0.2+/-0.07, and 0.09+/-0.03 nmol/hr per
      milligram of protein; and L-lactate production was 0.54+/-0.52, 0.06+/-0.04, and
      0.02+/-0 micromol/hr per milligram of protein respectively. CONCLUSIONS: Neonatal
      rat colon epithelial cells resemble adult colonocytes in their preference for
      butyrate as a metabolic substrate, indicating a constitutive expression of this
      property.

PMID- 9552141
TI  - Clinical quiz. Trichobezoar, a rare and unique form of gastrointestinal foreign
      body.

PMID- 9552142
TI  - The biology of inherited disorders of the gastrointestinal tract--part II:
      pancreatic and hepatobiliary disorders.

PMID- 9552143
TI  - The role of zinc and vitamin A in persistent diarrhea among infants and young
      children.

PMID- 9552144
TI  - Diffuse microcystic pancreatic enlargement in a cystic fibrosis patient causing
      severe gastrointestinal symptoms and successfully treated by total
      pancreatectomy.

PMID- 9552145
TI  - Epilepsy and Crohn's disease in children.

PMID- 9552146
TI  - Spontaneous perforation of the cystic duct.

PMID- 9552147
TI  - Superior mesenteric artery syndrome complicating mitochondrial encephalopathy.

PMID- 9552148
TI  - Eosinophils in the esophagus: acid is not the only cause.

PMID- 9552149
TI  - The difficulty with rapid communication: fulminant hepatic failure in infancy.

PMID- 9552150
TI  - The use of antineutrophil cytoplasmic antibodies to determine clinical patterns
      of ulcerative colitis in children.

PMID- 9552151
TI  - Generalised mitochondrial cytopathy is an absolute contraindication to orthotopic
      liver transplant in childhood.

PMID- 9552152
TI  - Site-directed gene therapy: a goal for the 21st century.

PMID- 9552153
TI  - Nutrition in children with cerebral palsy.

PMID- 9552154
TI  - A phosphoinositide-binding sequence is shared by PH domain target molecules--a
      model for the binding of PH domains to proteins.
AB  - Pleckstrin homology (PH) domains have been proven to bind phosphoinositides (PI)
      and inositolphosphates (IP). On the other hand, a binding of PH domains to
      proteins is still a matter of debate. The goal of this work was to identify
      potential PH domain protein target sites and to build a model for PH domain
      protein binding. A candidate sequence, called HIKE, was identified by sequence
      homology analysis of the proteins that are considered the strongest PH binding
      candidates, i.e., Gbeta, PKC, and Akt. HIKE contains a PI binding sequence and
      fulfills several criteria for a potential PH-binding site, i.e., it is present in
      other PH-binding candidates, lies in regulatory regions independently predicted
      to bind PH domains, and is conserved in 3-D structure among different molecules.
      These findings and the similarities with the mode of binding of PTB and PDZ
      domains suggest a beta strand-beta strand coordination model for PH-protein
      binding. The HIKE model predicts that membrane anchoring of PH domains and their
      targets could be a critical step in their interaction, which would consistently
      explain why PH-protein binding has only been detected in the presence of PI.

PMID- 9552155
TI  - Structure-based design of model proteins.
AB  - A structure-based, sequence-design procedure is proposed in which one considers a
      set of decoy structures that compete significantly with the target structure in
      being low energy conformations. The decoy structures are chosen to have strong
      overlaps in contacts with the putative native state. The procedure allows the
      design of sequences with large and small stability gaps in a random-bond
      heteropolymer model in both two and three dimensions by an appropriate assignment
      of the contact energies to both the native and nonnative contacts. The design
      procedure is also successfully applied to the two-dimensional HP model.

PMID- 9552156
TI  - Crystal structure of calcium-independent subtilisin BPN' with restored thermal
      stability folded without the prodomain.
AB  - The three-dimensional structure of a subtilisin BPN' construct that was produced
      and folded without its prodomain shows the tertiary structure is nearly identical
      to the wild-type enzyme and not a folding intermediate. The subtilisin BPN'
      variant, Sbt70, was cloned and expressed in Escherichia coli without the
      prodomain, the 77-residue N-terminal domain that catalyzes the folding of the
      enzyme into its native tertiary structure. Sbt70 has the high-affinity calcium
      binding loop, residues 75 to 83, deleted. Such calcium-independent forms of
      subtilisin BPN' refold independently while retaining high levels of activity
      [Bryan et al., Biochemistry, 31:4937-4945, 1992]. Sbt70 has, in addition, seven
      stabilizing mutations, K43N, M50F, A73L, Q206V, Y217K, N218S, Q271E, and the
      active site serine has been replaced with alanine to prevent autolysis. The
      purified Sbt70 folded spontaneously without the prodomain and crystallized at
      room temperature. Crystals of Sbt70 belong to space group P2(1)2(1)2(1) with unit
      cell parameters a = 53.5 A, b = 60.3 A, and c = 83.4 A. Comparison of the refined
      structure with other high-resolution structures of subtilisin BPN' establishes
      that the conformation of Sbt70 is essentially the same as that previously
      determined for other calcium-independent forms and that of other wild-type
      subtilisin BPN' structures, all folded in the presence of the prodomain. These
      findings confirm the results of previous solution studies that showed subtilisin
      BPN' can be refolded into a native conformation without the presence of the
      prodomain [Bryan et al., Biochemistry 31:4937-4945, 1992]. The structure analysis
      also provides the first descriptions of four stabilizing mutations, K43N, A73L,
      Q206V, and Q271E, and provides details of the interaction between the enzyme and
      the Ala-Leu-Ala-Leu tetrapeptide found in the active-site cleft.

PMID- 9552157
TI  - Recognition and interaction of small rings with the ricin A-chain binding site.
AB  - Ricin A-chain is an N-glucosidase that attacks ribosomal RNA at a highly
      conserved adenine residue. Our recent crystallographic studies show that not only
      adenine and formycin, but also pterin-based rings can bind in the active site of
      ricin. For a better understanding of the means by which ricin recognizes adenine
      rings, the geometries and interaction energies were calculated for a number of
      complexes between ricin and tautomeric modifications of formycin, adenine,
      pterin, and guanine. These were studied by molecular mechanics, semi-empirical
      quantum mechanics, and ab initio quantum mechanical methods. The calculations
      indicate that the formycin ring binds better than adenine and pterin better than
      formycin, a result that is consistent with the crystallographic data. A tautomer
      of pterin that is not in the low energy form in either the gas phase or in
      aqueous solution has the best interaction with the enzyme. The net interaction
      energy, defined as the interaction energy calculated in vacuo between the
      receptor and an inhibitor minus the solvation energy of the inhibitor, provides a
      good prediction of the ability of the inhibitor to bind to the receptor. The
      results from experimental and molecular modeling work suggest that the ricin
      binding site is not flexible and may only recognize a limited range of adenine
      like rings.

PMID- 9552158
TI  - Modeling of inhibitor-metalloenzyme interactions and selectivity using molecular
      mechanics grounded in quantum chemistry.
AB  - We investigated the binding properties of the metalloprotease inhibitors
      hydroxamate, methanethiolate, and methylphosphoramidate to a model coordination
      site occurring in several Zn2+ metalloproteases, including thermolysin. This was
      carried out using both the SIBFA (sum of interactions between fragments ab initio
      computed) molecular mechanics and the SCF/MP2 procedures for the purpose of
      evaluating SIBFA as a metalloenzyme modeling tool. The energy-minimized
      structures were closely similar to the X-ray crystallographic structures of
      related thermolysin-inhibitor complexes. We found that selectivity between
      alternative geometries and between inhibitors usually stemmed from multiple
      interaction components included in SIBFA. The binding strength sequence is
      hydroxamate > methanethiolate > or = methylphosphoramidate from multiple
      interaction components included in SIBFA. The trends in interaction energy
      components, rankings, and preferences for mono- or bidentate binding were
      consistent in both computational procedures. We also compared the Zn2+ vs. Mg2+
      selectivities in several other polycoordinated sites having various "hard" and
      "soft" qualities. This included a hexahydrate, a model representing Mg2+/Ca2+
      binding sites, a chlorophyll-like structure, and a zinc finger model. The latter
      three favor Zn2+ over Mg2+ by a greater degree than the hydrated state, but the
      selectivity varies widely according to the ligand "softness." SIBFA was able to
      match the ab initio binding energies by < 2%, with the SIBFA terms representing
      dispersion and charge-transfer contributing the most to Zn2+/Mg2+ selectivity.
      These results showed this procedure to be a very capable modeling tool for
      metalloenzyme problems, in this case giving valuable information about details
      and limitations of "hard" and "soft" selectivity trends.

PMID- 9552160
TI  - Prediction of the three-dimensional structure of proteins using the electrostatic
      screening model and hierarchic condensation.
AB  - We describe a method for predicting the three-dimensional (3-D) structure of
      proteins from their sequence alone. The method is based on the electrostatic
      screening model for the stability of the protein main-chain conformation. The
      free energy of a protein as a function of its conformation is obtained from the
      potentials of mean force analysis of high-resolution x-ray protein structures.
      The free energy function is simple and contains only 44 fitted coefficients. The
      minimization of the free energy is performed by the torsion space Monte Carlo
      procedure using the concept of hierarchic condensation. The Monte Carlo
      minimization procedure is applied to predict the secondary, super-secondary, and
      native 3-D structures of 12 proteins with 28-110 amino acids. The 3-D structures
      of the majority of local secondary and super-secondary structures are predicted
      accurately. This result suggests that control in forming the native-like local
      structure is distributed along the entire protein sequence. The native 3-D
      structure is predicted correctly for 3 of 12 proteins composed mainly from the
      alpha-helices. The method fails to predict the native 3-D structure of proteins
      with a predominantly beta secondary structure. We suggest that the hierarchic
      condensation is not an appropriate procedure for simulating the folding of
      proteins made up primarily from beta-strands. The method has been proved accurate
      in predicting the local secondary and super-secondary structures in the blind ab
      initio 3-D prediction experiment.

PMID- 9552159
TI  - Engineering of a stable mutant malic enzyme by introducing an extra ion-pair to
      the protein.
AB  - A double mutant (R9E/M17K) of pigeon liver malic enzyme with glutamate and lysine
      replaced for arginine and methionine at positions 9 and 17, respectively, was
      found to be much more stable in urea and thermal denaturation, but was
      enzymatically less active than the wild-type enzyme (WT). Unfolding of the enzyme
      by urea produced a large red shifting of the protein fluorescence maximum from
      320 to 360 nm, which was completely reversible upon dilution. Analysis of the
      denaturation curves monitored by enzyme activity lost suggested that a putative
      intermediate was involved in the denaturation process. The half unfolding urea
      concentration, measured by fluorescence spectral changes, increased from 2.24 M
      for WT to 3.13 M for R9E/M17K. The melting temperature increased by approximately
      10 degrees C for R9E/M17K compared with that for WT. Kinetic analysis of the
      thermal inactivation at 58 degrees C also conformed to a three-state model with
      the rate constant for the intermediate state of R9E/M17K (k2 = 0.03 min(-1))
      being much smaller than the WT value (k2 = 2.39 min(-1)). Results obtained from
      single mutants indicated that the decreasing enzyme activity of R9E/M17K was
      exclusively due to R9 mutation, which increased the K(mMn) and K(mMal) by at
      least one order of magnitude compared with WT. Consequently, a decrease occurred
      in the specificity constant [k(cat)/(K(mMm)K(mNADP)K(mMal))] for the R9 mutants
      at least four orders of magnitude smaller than the WT. M17K has similar
      properties to the WT, while R9E is more labile than the WT enzyme. The above
      results indicate that the extra stability gained by the double mutant possibly
      occurs through the introduction of an extra ion-pair between E9 and K17, which
      freezes the double mutant in the putative intermediate state. Examination of the
      N-terminal amino acid sequence of pigeon liver malic enzyme reveals that position
      15 is also a lysine residue. Since the R9E mutant, which has an extra Glu9-Lys15
      ion-pair, is less stable than the WT, we conclude that the contribution to malic
      enzyme stability is specific for the Glu9-Lys17 ion-pair.

PMID- 9552161
TI  - Prediction and classification of domain structural classes.
AB  - Can the coupling effect among different amino acid components be used to improve
      the prediction of protein structural classes? The answer is yes according to the
      study by Chou and Zhang (Crit. Rev. Biochem. Mol. Biol. 30:275-349, 1995), but a
      completely opposite conclusion was drawn by Eisenhaber et al. when using a
      different dataset constructed by themselves (Proteins 25:169-179, 1996). To
      resolve such a perplexing problem, predictions were performed by various
      approaches for the datasets from an objective database, the SCOP database
      (Murzin, Brenner, Hubbard, and Chothia. J. Mol. Biol. 247:536-540, 1995).
      According to SCOP, the classification of structural classes for protein domains
      is based on the evolutionary relationship and on the principles that govern the
      3D structure of proteins, and hence is more natural and reliable. The results
      from both resubstitution tests and jackknife tests indicate that the overall
      rates of correct prediction by the algorithm incorporated with the coupling
      effect among different amino acid components are significantly higher than those
      by the algorithms without using such an effect. It is elucidated through an
      analysis that the main reasons for Eisenhaber et al. to have reached an opposite
      conclusion are the result of (1) misusing the component-coupled algorithm, and
      (2) using a conceptually incorrect rule to classify protein structural classes.
      The formulation and analysis presented in this article are conducive to clarify
      these problems, helping correctly to apply the prediction algorithm and interpret
      the results.

PMID- 9552162
TI  - Zebrafish tenascin-W, a new member of the tenascin family.
AB  - A cDNA clone encoding tenascin-W, a novel member of the tenascin family, was
      isolated from a 20- to 28-h postfertilization (hpf) zebrafish cDNA library on the
      basis of the conserved epidermal growth factor-like domains represented in all
      tenascin molecules. An open reading frame of 2796 base pairs encodes a mature
      protein consisting of heptad repeats, a cysteine-rich amino terminal region, 3.5
      epidermal growth factor-like repeats, five fibronectin type III homologous
      repeats, and a domain homologous to fibrinogen. These domains are the typical
      modular elements of molecules of the tenascin family. Sequence comparison
      demonstrated that TN-W shares homologies with the members of the tenascin family
      but is not a species homolog of any identified tenascin. The expression pattern
      of tn-w was analyzed by in situ hybridization in 1-day-old embryos, in 3-day-old
      larvae, and in juvenile zebrafish. At 24-25 hpf, tn-w mRNA was expressed in the
      lateral plate mesoderm, most conspicuously in the presumptive sclerotome.
      Migrating cells of sclerotomal and neural crest origins also showed high levels
      of expression. At 3 days, expression by sclerotomal and neural crest cells
      continued to be observed while expression in the somitic mesoderm was decreased.
      In juvenile fish, tn-w was expressed weakly by cells in the myosepta and, more
      strongly, by presumably nonneuronal cells in the dorsal root ganglia. In these
      tissues and at the same developmental stages, the expression of tn-w partially
      overlapped with the distribution of tn-c mRNA. In addition, tn-c was expressed in
      the central nervous system (CNS) and in the axial mesoderm, neither of which
      expressed tn-w at any of the age stages examined. The expression pattern of tn-w
      suggests an involvement in neural crest and sclerotome cell migration and in the
      formation of the skeleton. Similar and possibly overlapping functions could also
      be performed by tn-c, which appears to have additional functions during the
      development of the CNS.

PMID- 9552163
TI  - Selective blockade of axonogenesis in cultured hippocampal neurons by the
      tyrosine phosphatase inhibitor orthovanadate.
AB  - Protein tyrosine phosphorylation has been implicated in several aspects of
      neurite outgrowth regulation. To address specific roles in early neuronal
      morphogenesis, hippocampal neurons in culture were treated with the tyrosine
      phosphatase inhibitor orthovanadate. This treatment completely suppressed axon
      formation, yet enhanced formation of minor neurites. The inhibition of
      axonogenesis was dose dependent and occurred in parallel with a marked increase
      in cellular phosphotyrosine immunoreactivity, which was especially concentrated
      within neuritic growth cones and showed partial colocalization with f-actin. Both
      the blockade of axonogenesis and the elevation of phosphotyrosine were completely
      reversible. An additional and unexpected effect of orthovanadate was the
      appearance of many binucleate neurons. Immunoblotting experiments using a
      phosphotyrosine-specific antibody revealed an orthovanadate-induced reversible
      hyperphosphorylation of several protein bands, especially of two at 115 and 125
      kD. These data suggest a potentially important role for tyrosine phosphatases and
      their phosphoprotein substrates in axonogenesis.

PMID- 9552164
TI  - Nicotine blocks TNF-alpha-mediated neuroprotection to NMDA by an alpha
      bungarotoxin-sensitive pathway.
AB  - Excitotoxic neuronal death mediated by N-methyl-D-aspartate (NMDA) glutamate
      receptors can contribute to the extended brain damage that often accompanies
      trauma or disease. Both the inflammatory cytokine tumor necrosis factor-alpha
      (TNF-alpha) and nicotine have been identified as possible neuroprotective agents
      to NMDA assault. We find that TNF-alpha protection of a subpopulation of cultured
      cortical neurons to chronic NMDA-mediated excitotoxic death requires both the
      activation of the p55/TNFRI, but not p75/TNFRII, and the release of endogenous
      TNF-alpha. Nicotine protection to NMDA was mediated through an alpha-bungarotoxin
      sensitive receptor. When coapplied, neuroprotection to NMDA by either TNF-alpha
      or nicotine was abolished but could be recovered with alpha-bungarotoxin. These
      results suggest that the cytokine TNF-alpha and alpha-bungarotoxin-sensitive
      nicotinic neurotransmitter receptors confer neuroprotection through potentially
      antagonistic pathways.

PMID- 9552165
TI  - Neurite outgrowth, RGD-dependent, and RGD-independent adhesion of identified
      molluscan motoneurons on selected substrates.
AB  - The extracellular matrix (ECM) provides structural support to cells and tissues
      and is involved in the regulation of various essential physiological processes,
      including neurite outgrowth. Most of the adhesive interactions between cells and
      ECM proteins are mediated by integrins. Integrins typically recognize short
      linear amino acid sequences in ECM proteins, one of the most common being
      Arginine-Glycine-Aspartate (RGD). The present study investigated neurite
      outgrowth and adhesion of identified molluscan neurons on a selection of
      substrates in vitro. Involvement of RGD binding sites in adhesion to the
      different substrates was investigated using soluble synthetic RGD peptides. The
      cells adhered to native (i.e., nondenatured) laminin and type IV collagen, but
      not to native plasma fibronectin. Denaturation of fibronectin dramatically
      enhanced cell adhesion. Only the adhesion to denatured fibronectin was inhibited
      by RGD peptides, indicating that denaturation uncovers a RGD binding site in the
      protein. Laminin as well as denatured fibronectin, but not type IV collagen,
      induced neurite outgrowth from a percentage of the RPA neurons. These results
      demonstrate that molluscan neurons can attach to various substrates using both
      RGD-dependent and RGD-independent adhesion mechanisms. This suggests that at
      least two different cell adhesion receptors, possibly belonging to the integrin
      family, are expressed in these neurons. Moreover, the results show that
      vertebrate ECM proteins can induce outgrowth from these neurons, suggesting that
      the mechanisms involved in adhesion as well as outgrowth promoting are
      evolutionarily well conserved.

PMID- 9552166
TI  - A detached branch stops being recognized as self by other branches of a neuron.
AB  - The multiple peripheral projections of a single leech mechanosensory neuron form
      individual arbors that do not overlap at all with each other, a phenomenon that
      has been termed "self-avoidance" (Yau, 1976; Kramer and Stent, 1985). This is in
      marked contrast to the peripheral arbors of adjacent segmental homologues, which
      partially overlap with each other at their boundaries in target areas of the body
      wall (Nicholls and Baylor, 1968; Gan and Macagno, 1995). How a neurite
      differentiates between sibling neurites of the same cell and those of a homologue
      is not known, but possible mechanisms include the recognition of surface markers
      of neuronal identity or the detection of cell-specific patterns of activity. In
      order to test whether this self-recognition requires a neurite to be in direct
      communication with its soma, we used a laser microbeam to sever a branch of a dye
      filled pressure-sensitive (P) neuron in an intact leech embryo. Time-lapse
      observations of the P cell arbor in the living, unanesthetized, animal for up to
      24 h following the surgery showed that the detached branch continued to show
      dynamic growth behavior throughout the period of observation. However, the
      detached branch ceased being avoided by the rest of the cell within a few hours,
      other, attached branches of the neuron overgrowing its territory and directly
      overlapping with it. Our experiments provide direct evidence for the existence of
      strong growth-inhibiting interactions between sibling processes, and indicate
      that self-avoidance by the growing neurites of a cell requires physical
      continuity between these neurites.

PMID- 9552167
TI  - Molecular characterization of NOS in a mollusc: expression in a giant modulatory
      neuron.
AB  - Here we report on the molecular characterization of the first molluscan NOS in
      the CNS of the pond snail Lymnaea stagnalis. This Lymnaea NOS (Lym-nNOS) which is
      expressed preferentially in the CNS is most similar to mammalian neuronal NOS but
      contains tandem repeats of a seven amino acid motif not found in any other known
      NOS. We have localized Lym-nNOS to the serotonergic cerebral giant cells (CGCs)
      which modulate synaptic transmission within a neural network that generates
      feeding behavior. Our results suggest that the CGCs employ both NO and serotonin
      in the modulation of the central neural network underlying feeding.

PMID- 9552168
TI  - Midline Fasciclin: a Drosophila Fasciclin-I-related membrane protein localized to
      the CNS midline cells and trachea.
AB  - Drosophila Fasciclin I is the prototype of a family of vertebrate and
      invertebrate proteins that mediate cell adhesion and signaling. The midline
      fasciclin gene encodes a second Drosophila member of the Fasciclin I family.
      Midline Fasciclin largely consists of four 150 amino acid repeats characteristic
      of the Fasciclin I family of proteins. Immunostaining and biochemical analysis
      using Midline Fasciclin antibodies indicates that it is a membrane-associated
      protein, although the sequence does not reveal a transmembrane domain. The gene
      is expressed in a dynamic fashion during embryogenesis in the blastoderm, central
      nervous system midline cells, and trachea, suggesting it plays multiple
      developmental roles. Protein localization studies indicate that Midline Fasciclin
      is found within cell bodies of midline neurons and glia, and on midline axons.
      Initial cellular analysis of a midline fasciclin loss-of-function mutation
      reveals only weak defects in axonogenesis. However, embryos mutant for both
      midline fasciclin and the abelson nonreceptor tyrosine kinase, show more severe
      defects in axonogenesis that resemble fasciclin I abelson double mutant
      phenotypes.

PMID- 9552169
TI  - Metabotropic glutamate receptor expression in olfactory receptor neurons from the
      channel catfish, Ictalurus punctatus.
AB  - Metabotropic glutamate receptors (mGluRs) were identified in olfactory receptor
      neurons of the channel catfish, Ictalurus punctatus, by polymerase chain
      reaction. DNA sequence analysis confirmed the presence of two subtypes, mGluR1
      and mGluR3, that were coexpressed with each other and with the putative odorant
      receptors within single olfactory receptor neurons. Immunocytochemical data
      showed that both mGluR subtypes were expressed in the apical dendrites and some
      cilia of olfactory neurons. Pharmacological analysis showed that antagonists to
      each mGluR subtype significantly decreased the electrophysiological response to
      odorant amino acids. alpha-Methyl-L-CCG1/(2S,3S,4S)-2-methyl-2
      (carboxycyclopropyl++ +)glycine (MCCG), a known antagonist to mGluR3, and (S)-4
      carboxyphenylglycine (S-4CPG), a specific antagonist to mGluR1, each
      significantly reduced olfactory receptor responses to L-glutamate. S-4CPG and
      MCCG reduced the glutamate response to 54% and 56% of control, respectively,
      which was significantly greater than their effect on a neutral amino acid
      odorant, methionine. These significant reductions of odorant response by the
      antagonists, taken with the expression of these receptors throughout the
      dendritic and ciliated portions of some olfactory receptor neurons, suggest that
      these mGluRs may be involved in olfactory reception and signal transduction.

PMID- 9552170
TI  - The shaking B gene in Drosophila regulates the number of gap junctions between
      photoreceptor terminals in the lamina.
AB  - The molecular structure of insect gap junctions differs from that in vertebrates,
      and in Drosophila is possibly encoded by the shaking B (= Passover) locus.
      shaking B2 is a null allele that acts in the nervous system. In the shakB2
      mutant, one site of action are gap junctions between photoreceptor terminals in
      the cartridges of the lamina, beneath the compound eye, which we assayed from the
      number of close-apposition profiles in thin-section EM. The number of profiles in
      the Canton-S (C-S) wild type is about 0.5 per cartridge per section in distal and
      mid-lamina depths, and significantly less, about one quarter this value, closer
      to the brain, in the proximal lamina. In shakB2, there are fewer profiles,
      approximately one quarter the number of appositions in distal and mid-lamina
      depths as in C-S, and their number does not differ significantly from those at
      the proximal depth in either the mutant or wild type. Thus mutant action is
      associated with a reduced number of appositions at distal and mid-lamina depths.
      We propose that R1-R6 gap junctions are partitioned into at least two strata,
      proximal and distal, and that two populations of gap junctions exist, one
      extending throughout the lamina that does not require shakB, and a second at
      distal and mid-depth levels, which does. The number of gap junctions is reduced
      in mutant shakB2, and surviving appositions at distal and middle lamina depths
      possibly have wider clefts than in C-S. Gap junctions are reduced equally between
      all R1-R6 terminals, so the two different types of junction proposed, shakB2- and
      non-shakB2-dependent, can apparently express in a single receptor terminal.

PMID- 9552171
TI  - Synaptic connections between GABA-immunoreactive neurons and uniglomerular
      projection neurons within the antennal lobe of the cockroach, Periplaneta
      americana.
AB  - Synapses within deutocerebral glomeruli between GABA-immunoreactive, putatively
      inhibitory local interneurons and uniglomerular projection (output) neurons were
      demonstrated by means of a combination of GABA-immunogold labeling and
      intracellular HRP injection. The following connections were identified. 1) GABA
      immunoreactive (GABAir) neurons form output synapses in a dyadic fashion onto a
      uniglomerular projection neuron and, in addition, a second GABAir neuron. A
      uniglomerular projection neuron in turn forms dyadic output synapses onto two
      GABAir neurons. Several examples of reciprocal connections have been identified
      between, first, GABAir neurons and uniglomerular projection neurons, and, second,
      GABAir neurons themselves. 2) GABAir neurons are serially connected with
      uniglomerular projection neurons via interposed GABAir processes. In some cases,
      also the first GABAir process of such a polysynaptic connection formed an output
      synapse onto the projection neuron. Such serial connections may form the
      structural basis for both, the feedforward inhibition as well as the feedforward
      disinhibition of uniglomerular projection neurons by GABAergic neurons. The
      reciprocal contacts may serve as control devices that modulate the output
      activity of the projection neurons.

PMID- 9552172
TI  - Phencyclidine (PCP) and dizocilpine (MK801) exert time-dependent effects on the
      expression of immediate early genes in rat brain.
AB  - The mRNA expression pattern for four different immediate early genes was examined
      dynamically in rat brain after administration of phencyclidine (PCP; 0.86 or 8.6
      mg/kg) or MK801 (0.1 or 1.0 mg/kg). Following each treatment, the expression of
      cfos, cjun, junB, and zif268 mRNA changed distinctively and dynamically between 1
      and 48 hours. cfos mRNA was induced in cortical areas at early times after either
      dose of PCP or of MK801; the change was especially prominent in cingulate and
      auditory cortices. zif268 mRNA showed an early (1 hour) activation and a delayed
      (24-48 hour) suppression after PCP and MK801 in neocortical areas. PCP also
      caused cjun and junB mRNA induction in cortical areas at early times, with a
      distribution and time course similar to its effects on cfos mRNA. No alterations
      in cfos, cjun, or junB mRNA were found in neocortical or hippocampal areas at any
      delayed time (>6 hours) after PCP treatment, whereas suppression of zif268
      expression was prominent even at 48 hours post-treatment. CPP, a competitive NMDA
      antagonist, showed a similar pattern of effects on cfos and zif268 mRNA
      expression. These functional consequences of a PCP- or MK801-induced reduction in
      NMDA-sensitive glutamate transmission may be relevant to an understanding of
      animal NMDA pharmacology and/or to clinical psychotomimetic side effects of
      antiglutamatergic treatments.

PMID- 9552173
TI  - Neurotransmitter regulation of MAP kinase signaling in striatal neurons in
      primary culture.
AB  - Glutamate and dopamine are important neurotransmitters in the basal ganglia.
      Dopamine can act via D1 receptors to activate adenylyl cyclase in striatal
      neurons, while glutamate stimulation of NMDA receptors leads to an increase in
      intracellular calcium. Increases in intracellular calcium or cAMP can induce
      immediate early gene expression in striatal neurons. In the present study, NMDA
      receptor stimulation or adenylyl cyclase activation resulted in the activation of
      MAP kinase in striatal neurons in primary culture. The effect of cAMP appeared to
      involve cAMP-dependent protein kinase, in addition to a tyrosine kinase and MEK.
      NMDA-induced MAP kinase activation was also dependent on a tyrosine kinase and
      MEK. The EGF receptor, which has been implicated in calcium- and G protein
      induced MAP kinase activation, did not mediate the effects of NMDA or forskolin
      on MAP kinase. Furthermore, the src kinase inhibitor, herbimycin A, and the
      phosphoinositol-3-kinase inhibitor, wortmannin, did not prevent MAP kinase
      activation by these stimuli. However, the ability of both NMDA and forskolin to
      activate MAP kinase in striatal neurons was blocked by SB 203580, an inhibitor of
      p38 reactivating kinase. These results indicate that both NMDA receptor
      activation and elevations in cAMP can result in MEK-induced MAP kinase activation
      in striatal neurons. However, the signal transduction pathways mediating these
      responses appear to be distinct from those known to mediate MAP kinase activation
      by other stimuli.

PMID- 9552174
TI  - Compartmental analysis of dopa decarboxylation in living brain from dynamic
      positron emission tomograms.
AB  - The trapping of decarboxylation products of radiolabelled dopa analogs in living
      human brain occurs as a function of the activity of dopa decarboxylase. This
      enzyme is now understood to regulate, with tyrosine hydroxylase, cerebral
      dopamine synthesis. Influx into brain of dopa decarboxylase substrates such as 6
      [18F]fluorodopa and beta-[11C]dopa measured by positron emission tomography can
      be analyzed by solution of linear differential equations, assuming irreversible
      trapping of the decarboxylated products in brain. The isolation of specific
      physiological steps in the pathway for catecholamine synthesis requires
      compartmental modelling of the observed dynamic time-activity curves in plasma
      and in brain. The several approaches to the compartmental modelling of the
      kinetics of labelled substrates of dopa decarboxylase are now systematically and
      critically reviewed. Labelled catechols are extensively metabolized by hepatic
      catechol-O-methyltransferase yielding brain-penetrating metabolites. The
      assumption of a fixed blood-brain permeability ratio for O-methyl-6
      [18F]fluorodopa or O-methyl-beta-[11C]dopa to the parent compounds eliminates
      several parameters from compartmental models. However, catechol-O
      methyltransferase activity within brain remains a possible factor in
      underestimation of cerebral dopa decarboxylase activity. The O-methylation of
      labelled catechols is blocked with specific enzyme inhibitors, but dopa
      decarboxylase substrates derived from m-tyrosine may supplant the catechol
      tracers. The elimination from brain of decarboxylated tracer metabolites can be
      neglected without great prejudice to the estimation of dopa decarboxylase
      activity when tracer circulation is less than 60 minutes. However, elimination of
      dopamine metabolites from brain occurs at a rate close to that observed
      previously for metabolites of glucose labelled in the 6-position. This phenomenon
      can cause systematic underestimation of the rate of dopa decarboxylation in
      brain. The spillover of radioactivity due to the limited spatial resolution of
      tomographs also results in underestimation of dopa decarboxylase activity, but
      correction for partial volume effects is now possible. Estimates of dopa
      decarboxylase activity in human brain are increased several-fold by this
      correction. Abnormally low influx of dopa decarboxylase tracers in the basal
      ganglia is characteristic of Parkinson's disease and other movement disorders.
      Consistent with postmortem results, the impaired retention of labelled dopa is
      more pronounced in the putamen than in the caudate nucleus of patients with
      Parkinson's disease; this heterogeneity persists after correction for spillover.
      Current in vivo assays of dopa decarboxylase activity fail to discriminate
      clinically distinct stages in the progression of Parkinson's disease and are, by
      themselves, insufficient for differential diagnosis of Parkinson's disease and
      other subcortical movement disorders. However, potential new avenues for
      therapeutics can be tested by quantifying the rate of metabolism of exogenous
      dopa in living human brain.

PMID- 9552175
TI  - Modulation of the neuronal response to N-methyl-D-aspartate by selective sigma2
      ligands.
AB  - It has now been accepted for several years that sigma (sigma) receptors exist in,
      at least, two distinct entities denoted sigma1 and sigma2. Previous
      electrophysiological studies from our laboratory have demonstrated that several
      selective sigma1 ligands potentiate the neuronal response to NMDA. The
      nonselective sigma1/sigma2 ligand DTG also potentiates the NMDA response.
      However, when DTG is administered at doses between 3 and 40 microg/kg, the
      increase of NMDA-induced activation turns to an epileptoid activity. Until
      recently, the physiological role of sigma2 receptors had been less studied due to
      the lack of selective sigma2 ligands. The goal of the present
      electrophysiological studies was to assess the effect of the intravenous
      administration of new selective sigma2 ligands on the neuronal response to NMDA
      in the CA3 region of the rat dorsal hippocampus. Lu 28-179 and BD 1008
      potentiated dose-dependently the NMDA response and generated bell-shaped dose
      response curves. These ligands failed to generate any epileptoid activity on
      their own but the subsequent administration of a low dose of a sigma1 agonist (JO
      1784) induced an epileptoid activity. Interestingly, the potentiations of the
      NMDA response induced by Lu 28-179 or BD 1008 were not reversed by haloperidol,
      by the neurosteroid progesterone, nor by the selective sigma1 antagonist NE-100.
      Ibogaine, a high affinity sigma2 ligand, slightly increases the NMDA response,
      which was reversed by progesterone. These data suggest that, similarly to sigma1
      ligands, sigma2 agonists potentiate the NMDA response and that the coactivation
      of sigma1 and sigma2 receptors could be necessary to induce an epileptoid
      activity. They also suggest that haloperidol may not act as a sigma2 antagonist
      and that several subtypes of sigma2 receptors could exist.

PMID- 9552176
TI  - Blockade of the reward-potentiating effects of nicotine on lateral hypothalamic
      brain stimulation by chlorisondamine.
AB  - Chlorisondamine, a quarternary nicotinic antagonist, was given in a dose that
      crosses the blood-brain barrier, is taken up and concentrated intracellularly by
      dopaminergic neurons, and induces long-term blockade of the locomotor stimulant
      and rewarding effects of nicotine. This treatment had no effect on the rewarding
      effects of lateral hypothalamic brain stimulation, failing to shift the function
      that relates reward strength to rate of responding (rate-frequency function).
      That the treatment regimen was sufficient to block nicotinic receptors in the
      reward system was confirmed by the fact that it completely blocked the ability of
      normally effective nicotine to potentiate the rewarding effects of stimulation
      (shift this function to the left). These data add evidence that the direct,
      endogenous cholinergic contribution to brain stimulation reward is muscarinic and
      fit with other evidence that the potentiation of brain stimulation reward by
      exogenous nicotine involves actions on nicotinic receptors native to dopaminergic
      neurons.

PMID- 9552177
TI  - Effect of social status on striatal dopamine D2 receptor binding characteristics
      in cynomolgus monkeys assessed with positron emission tomography.

PMID- 9552178
TI  - Human influenza viral infection in utero increases nNOS expression in hippocampi
      of neonatal mice.
AB  - We investigated the role of maternal exposure to human influenza virus (HI) in
      C57BL/6 mice on day 9 of pregnancy on hippocampal expression of nNOS in day 0
      neonates and compared that to sham-infected pups. Qualitative analysis using
      polyclonal antibody to nNOS showed overall increases in immunoreactivity (IR) in
      hippocampal and dentate layers of day 0 infected neonates when compared to sham
      infected animals. These increases in nNOS immunoreactivity were pronounced in
      hippocampal plate, intermediate, molecular, subplate, and dentate areas.
      Quantitative analysis of specific immunogold silver-enhanced nNOS IR via
      densitometry showed nNOS IR increases of 26-71.6% in all layers, i.e.,
      hippocampal plate (35.1%), dentate area (71.6%), molecular area (43.75%),
      subplate (45.7%), and intermediate zone (26%) in infected neonatal brains vs.
      controls. The changes in levels of nNOS expression in hippocampi of neonates born
      to mothers exposed to HI virus during the second trimester of pregnancy may
      reflect the potential for glutamatergic excitotoxicity via activation of NMDA
      receptors in the developing brains of these neonatal mice.

PMID- 9552179
TI  - The developing prefrontal cortex: is there a transient interneuron that
      stimulates catecholamine terminals?

PMID- 9552180
TI  - Classifying waste by reducing its generation.

PMID- 9552181
TI  - Biohazardous waste: risk assessment, policy, and management.

PMID- 9552182
TI  - Bacillus of Calmette and Guerin vaccination for tuberculosis prevention in
      healthcare workers: how good is good enough?

PMID- 9552183
TI  - A viral gastroenteritis outbreak associated with person-to-person spread among
      hospital staff.
AB  - OBJECTIVE: To identify the etiologic agent and risk factors associated with a
      hospital ward outbreak of gastroenteritis. SETTING: A regional referral hospital
      in upstate South Carolina. METHODS: We reviewed patient charts, surveyed staff,
      and tested stool from acutely ill persons. A case was defined as diarrhea and
      vomiting in a staff member or patient from January 5 to 13, 1996. RESULTS: The
      initial case occurred on January 5 in a staff nurse who subsequently was
      hospitalized on the ward and visited by many staff colleagues. The staff were at
      a significantly greater risk for gastroenteritis than were patients (28/89 [31%]
      vs 10/91 [11%]; relative risk [RR], 2.9; 95% confidence interval [CI95], 1.5
      5.5). All 10 case-patients had been exposed to case-nurses (assigned nurses who
      were primary caretakers), and eight had documented exposure to case-nurses 1 to 2
      days before their illness. Patients exposed to case-nurses had a significantly
      increased risk of illness (8/57 [14%] vs 0/32; RR, >4.5; CI95, undefined).
      Neither staff nor patients had significantly increased risk from food, water,
      ice, or exposure to case-patients. Electron microscopy identified small round
      structured viruses (SRSVs) in nine of nine stool samples. CONCLUSION: This
      nosocomial outbreak of gastroenteritis was likely caused by SRSVs introduced by a
      staff member and spread via person-to-person transmission from and among staff.
      The potential for spread of SRSV-associated gastroenteritis from and among staff
      should be considered in developing strategies to prevent similar outbreaks in
      hospital settings.

PMID- 9552184
TI  - Low risk for tuberculosis in a regional pediatric hospital: nine-year study of
      community rates and the mandatory employee tuberculin skin-test program.
AB  - OBJECTIVE: To assess the risk of Mycobacterium tuberculosis infection and disease
      among patients and workers in a regional pediatric hospital. DESIGN: Descriptive
      epidemiological study of the mandatory tuberculin skin testing program of
      hospital employees at hire and during annual reevaluation, pediatric patients
      with tuberculosis (TB), efficacy of hospital infection control measures, and
      community rates of TB. SETTING: 361-bed, university, pediatric hospital serving
      Cincinnati (1.7 million population). RESULTS: During 1986 through 1994, 2,275 to
      4,356 employees were compliant with Mantoux skin testing and screening each year.
      This represented >97% of the population who were eligible for screening. The
      cumulative rate of M tuberculosis infection from a previous positive tuberculin
      skin test was 10% to 12% per year during 1986 through 1994. Among new Mantoux
      skin-test converters in employees at annual reevaluation, the risk of TB
      infection was 0.3% in 1993 and 1994. There were no active cases of TB identified
      during new employee screening or annual reevaluation. Of 62 new Mantoux skin-test
      converters in 9 years, 23% were foreign-born, 13% were Asian, 23% were African
      American, 11% received the bacillus of Calmette-Guerin vaccine, and 60% had
      direct patient care or indirect patient contact. A cluster of five converters
      occurred in a department with no patient care or contact. Mantoux conversion
      rates were 1.9 per 1,000 employee patient-care or contact-years and 2.2 per 1,000
      employee non-patient-contact years. Twenty pediatric patients with active TB were
      identified during 1991 to 1994, with < or =6 cases per year, placing this
      hospital in the low-risk category for M tuberculosis disease. Three children with
      pulmonary TB were admitted without immediate respiratory isolation, possibly
      exposing 9 patients and 42 employees; none converted their Mantoux skin tests on
      retesting. Rates of active TB in Cincinnati were stable during the period (eg,
      8/100,000 population in 1994). CONCLUSIONS: Despite intense active surveillance
      among thousands of hospital employees with >97% annual compliance, tuberculin
      conversion rates were low, and no cases of active TB were identified during 9
      years of follow-up. There was no evidence of transmission of M tuberculosis from
      infected patients to employees during uncontrolled exposures. Rates of TB in the
      community were low. These data suggest that rigorous application of the Centers
      for Disease Control and Prevention guidelines and Occupation Safety and Health
      Administration regulations for preventing nosocomial TB in pediatric hospitals
      may be excessive and costly. Special provisions should be made for pediatric
      hospitals with a proven low risk of transmission of M tuberculosis.

PMID- 9552185
TI  - Can hospital discharge diagnosis be used for surveillance of bacteremia? A data
      quality study of a Danish hospital discharge registry.
AB  - OBJECTIVE: To assess the data quality of septicemia and sepsis registration in a
      hospital discharge registry in the County of Northern Jutland, Denmark. DESIGN:
      Comparison of data from the discharge registry of an 880-bed, public, urban
      hospital in the County of Northern Jutland with data from a computerized
      bacteremia database at the regional department of clinical microbiology. SETTING:
      Urban hospital with approximately 45,000 admissions per year. PATIENTS: The study
      included 406 episodes of bacteremia in the bacteremia database and 83 discharges
      with the diagnosis of septicemia registered in the hospital discharge registry
      between January 1, 1994, and December 31, 1994. INTERVENTIONS: None. RESULTS:
      Eighteen episodes were registered in both the hospital discharge registry and the
      bacteremia database. Using the bacteremia database as reference standard, the
      sensitivity for the diagnosis of septicemia in the hospital discharge registry
      was 4.4% (18/406; 95% confidence intervals [CI95, 2.4%-6.4%]). By review of
      hospital records, we estimated the positive predictive value of septicemia
      registration in the hospital discharge registry as 21.7% (18/83; CI95, 12.8%
      30.5%). No blood culture had been obtained in 44.4% (36/81; CI95, 33.6%-55.3%) of
      the cases with a discharge diagnosis of septicemia. In 33.3% (27/81; CI95, 23.1%
      43.6%), the discharge diagnosis of septicemia was given, although blood cultures
      were negative. CONCLUSIONS: The hospital discharge registry revealed numerous
      misclassifications, and the system was found not suited for surveillance of, or
      research in, bacteremia at present.

PMID- 9552186
TI  - Carriage of methicillin-resistant Staphylococcus aureus at hospital admission.
AB  - OBJECTIVES: To measure the prevalence of, and to establish predictors for, the
      nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) at hospital
      admission. To evaluate mannitol-salt agar with oxacillin for the simultaneous
      detection and identification of MRSA from nasal swabs. DESIGN: Three-month
      prospective case-control survey, with data collected from interviews and
      computerized databases. The criterion standard for MRSA detection was culture on
      Mueller-Hinton agar with oxacillin 6 microg/mL (National Committee for Clinical
      Laboratory Standards method). SETTING: 320-bed tertiary-care hospital. PATIENTS:
      387 patients screened within 24 hours after admission, including 10 MRSA carriers
      (cases), 291 patients with no S aureus, and 86 patients with methicillin
      susceptible S aureus. RESULTS: The prevalence of MRSA nasal carriage was 2.6%,
      whereas the prevalence of carriage was 3.1% when both nasal and wound cultures
      were performed. The significant predictors of carriage were a prior detection of
      MRSA, open wounds, diabetes mellitus, treatments by injection, prior nursing home
      stays, visits at home by a nurse, and prior antibiotic treatments. Cases had
      stayed for longer periods in hospitals and had received longer antibiotic
      treatments within a year. Eighty patients (including the 10 cases) had diabetes,
      had been exposed to healthcare facilities within a year, and had antibiotics
      within 6 months. The sensitivity and negative predictive value of nasal swabs on
      mannitol-salt agar with oxacillin were 60% and 71%, respectively. CONCLUSION:
      MRSA carriage on admission to the hospital may be an increasing and
      underestimated problem. Further studies are needed to develop and validate a
      sensitive and specific prediction rule.

PMID- 9552187
TI  - Risk factors associated with the acquisition of amikacin-resistant gram-negative
      bacilli in central New Jersey hospitals.
AB  - A case-control study was performed in central New Jersey hospitals to evaluate
      the potential patient factors associated with the acquisition of amikacin
      resistant gram-negative bacilli (ARGNB). Univariate analysis revealed an
      association between numerous patient factors, and multivariate analysis revealed
      four factors to be associated independently with ARGNB: the number of hospital
      admissions during the prior year, previous aminoglycoside exposure, intubation,
      and intensive-care-unit admission.

PMID- 9552188
TI  - Colonization by Acinetobacter baumanii in intensive-care-unit patients.
AB  - We prospectively studied the value of systematic rectal swabs performed for the
      detection of colonization and the prediction of infections by Acinetobacter
      baumanii in 751 consecutive patients admitted to five intensive-care units (ICUs)
      over an 8-month period. Gastrointestinal tract colonization was found in 8.7% of
      ICU admissions. The positive and negative predictive values of rectal swabs for
      the detection of subsequent infection were 17% and 99%, respectively. Sensitivity
      and specificity were 55% and 93%, respectively. We also determined the
      comparative values of rectal or nasal swabs and skin cultures for the detection
      of A baumanii colonization in 25 patients already colonized or infected with A
      baumanii. The combination of rectal and nasal swabs was positive in 20 (80%) of
      25. The results of the present study suggest that detection of gastrointestinal
      tract A baumanii colonization is not an accurate predictor of subsequent A
      baumanii infection and that combined rectal and nasal swabs might be used for the
      detection of A baumanii colonization in ICU patients.

PMID- 9552189
TI  - In support of bacillus of Calmette and Guerin for healthcare workers.
AB  - Although widely used outside the United States, bacillus of Calmette and Guerin
      (BCG) immunization generally is given scant consideration in the US literature.
      We believe that the recent resurgence of tuberculosis, including multidrug
      resistant tuberculosis, is a compelling argument for the use of BCG in healthcare
      workers and that BCG given to those at risk of exposure could be more effective
      than routine tuberculin skin testing and isoniazid prophylaxis

PMID- 9552190
TI  - Statistical quality control methods in infection control and hospital
      epidemiology, part I: Introduction and basic theory.
AB  - This article is the first in a two-part series discussing and illustrating the
      application of statistical process control (SPC) to processes often examined by
      hospital epidemiologists. The basic philosophical and theoretical foundations of
      statistical quality control and their relation to epidemiology are emphasized in
      order to expand mutual understanding and cross-fertilization between these two
      disciplines. Part I provides an overview of quality engineering and SPC,
      illustrates common types of control charts, and provides references for further
      information or statistical formulae. Part II discusses statistical properties of
      control charts, issues of chart design and optimal control limit widths,
      alternate possible SPC approaches to infection control, some common
      misunderstandings, and more advanced issues. The focus of both articles is mostly
      non-mathematical, emphasizing important concepts and practical examples rather
      than academic theory and exhaustive calculations.

PMID- 9552191
TI  - Guidelines for antiretrovirals in pediatric HIV.

PMID- 9552193
TI  - How fat is too fat?

PMID- 9552192
TI  - FDA approves new sterilants.

PMID- 9552194
TI  - More ways to stay dry.

PMID- 9552195
TI  - Psoriasis.

PMID- 9552196
TI  - Dietary fat reconsidered.

PMID- 9552197
TI  - I am 70 and have a cholesterol level of 250 mg/dl. Am I right to be concerned?

PMID- 9552199
TI  - Back in August 1996 you ran an article about an outpatient alternative to
      hysterectomy called balloon ablation. When I called the number you gave to enroll
      in a clinical trial of this procedure, I found that the number had been
      disconnected. What's going on?

PMID- 9552198
TI  - I have found vaginal estrogen cream to be very effective for vaginal dryness but
      am concerned about the long-term effects of using it. Are there any other
      treatments that work well for this?

PMID- 9552221
TI  - Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in
      active ulcerative colitis.
AB  - The inflammatory activity of colonic mucosal lesions may be stimulated by
      intraluminal bacteria. Our aim was to investigate whether administration of broad
      spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To
      this end, we performed a randomized, 5-day study with either oral enterically
      coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v.
      methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v.
      methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients
      with clinically active ulcerative colitis. Before and after 5 days of treatment,
      intestinal inflammation was assessed by the quantification of mucosal release of
      eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2
      excretion after oral lactulose was determined as an index of metabolic activity
      of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids
      significantly decreased in patients treated with antibiotic or steroids and
      antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2
      excretion. In conclusion, short-term treatment with enteric-coated amoxicillin
      clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory
      mediators.

PMID- 9552222
TI  - Quality-of-life factors in adolescent inflammatory bowel disease.
AB  - Little is known about the specific psychosocial factors that influence quality of
      life in adolescents with newly diagnosed inflammatory bowel disease (IBD). We
      adapted a model by Garrett and Drossman to assess adolescent adjustment to recent
      onset IBD. Thirty adolescent-parent pairs completed a set of standardized
      questionnaires. The inclusion criteria were adolescents 12-18 years of age with
      Crohn's disease or ulcerative colitis of < 5 years' duration. Adolescents' health
      related quality-of-life scores significantly correlated with satisfaction and
      degree of closeness with their social support members, such as parents. An
      unexpected finding was that the adolescents included more extended family than
      peers in their social support networks. Also of note was that parental coping
      styles rather than adolescent coping styles significantly correlated with
      adolescents' quality-of-life health scores. Severity of illness did not correlate
      with adolescent quality-of-life health scores. There was significant agreement
      between adolescent and parental quality-of-life health scores and stressful event
      ratings. Adolescents with recent-onset IBD rely more on family members than their
      peers for emotional support, and they depend more on their parents' coping skills
      than their own. These findings may indicate lags in normal adolescent
      development. Adolescents and parents do communicate and share concerns with each
      other. Support programs for adolescents with IBD should reinforce existing coping
      skills and parent-adolescent communication while promoting normative development.

PMID- 9552223
TI  - Mucin secretion in inflammatory bowel disease: comparison of a macrophage-derived
      mucin secretagogue (MMS-68) to conventional secretagogues.
AB  - We have described a novel macrophage-derived mucin secretagogue (MMS-68) that
      mediates mucin secretion in colon cancer cell lines and explants of normal and
      inflammatory bowel disease (IBD) mucosa. We compared MMS-68 induced mucin release
      with other known intestinal mucin secretagogues in normal colon explants and in
      the HT-29 colon cancer cell line, and to study the effects of MMS-68 on mucin
      release from inflamed and uninflamed ulcerative colitis (UC) and Crohn's disease
      (CD) mucosa. In normal colonic explants and HT-29 cells, each of the
      secretagogues including, MMS-68-induced mucin release two- to fivefold more than
      culture medium alone. In HT-29 cells, MMS-68 plus leukotriene C4 (LTC4) induced a
      50% increase in mucin release over either secretagogue alone, and MMS-68 plus
      platelet-activating factor (PAF) markedly enhanced mucin release by eightfold
      over either secretagogue. In colonic explants from patients with UC and CD, the
      mucin release in response to MMS-68 was similar to that of normal colonic
      explants. Likewise, in isolated epithelial cells from CD and UC (whether involved
      or uninvolved), MMS-68-induced release was similar to that of epithelial cells
      isolated from normal colonic mucosa. The number of MMS-68-producing macrophages
      was lower in uninflamed UC mucosa compared with inflamed UC mucosa and CD mucosa.
      The mucin secretagogue activity of MMS-68 is comparable to that of other known
      secretagogues, and PAF can have a synergistic effect on this activity. Whole
      tissue explants and isolated colonic epithelial cells from patients with IBD
      respond at least as well as their normal counterparts to MMS-68. MMS-68 may play
      a role in mucin secretion in normal and inflamed colonic tissue.

PMID- 9552224
TI  - The presence of anti-neutrophil antibodies reflects clinical and genetic
      heterogeneity within inflammatory bowel disease.
AB  - A detailed investigation of the relationship between anti-neutrophil cytoplasmic
      antibodies (ANCA) status, HLA genotype, and clinical patterns of inflammatory
      bowel disease was carried out, involving 236 European patients resident in the
      United Kingdom [120 had ulcerative colitis (UC), 116 had Crohn's disease (CD)].
      ANCA status was determined on coded plasma samples in Los Angeles using a two
      stage assay [fixed neutrophil enzyme-linked immunosorbent assay (ELISA) and
      indirect immunofluorescence], and HLA genotyping was carried out by polymerase
      chain reaction. The results provide evidence that ANCA reflect clinical and
      genetic heterogeneity within the inflammatory bowel diseases. In the UC patients,
      78.3% were ANCA positive [64.2 perinuclear (pANCA)], but only 46.5% CD patients
      were ANCA positive (19.3% pANCA). Furthermore, mean ELISA binding was
      significantly lower in CD (14.5% +/- 18.8% versus 40.5% +/- 41.0% in UC, p = 2.31
      x 10(-9)). Only 15 CD samples, all from patients with colonic disease, displayed
      ELISA > 20%; and the six CD patients with highest ELISA binding had clinical
      features very similar to ulcerative colitis. Moreover, in UC, significant
      relationships between ANCA status and genotype were noted. Thus, 92.7% of
      patients with the DR3 DQ2 TNF2 haplotype were ANCA positive [p = 0.03 versus DR3
      DQ2 TNF2-negative patients (73.9%)]. ELISA binding was increased in DR3 DQ2 TNF2
      positive patients (56.0 versus 35.7%, p = 0.02). In this population of UC, ANCA
      was not associated with DR2, DR4, or clinical pattern. These data emphasize the
      many factors that need to be considered in genetic marker studies in inflammatory
      bowel disease. Extensive disease heterogeneity, ethnicity, and methodological
      differences in ANCA detection are all pertinent.

PMID- 9552225
TI  - Severe knee pain as the single symptom of CMV infection in acute ulcerative
      colitis treated with cyclosporine.
AB  - We describe a case of systemic cytomegalovirus (CMV) infection in an ulcerative
      colitis patient admitted to the hospital for an acute flare-up of his colitis. He
      was treated with combination immunosuppressive therapy including i.v.
      cyclosporine and corticosteroids and PO azathioprine. Severe bilateral stabbing
      knee pain was the only manifestation of CMV disease, which quickly responded to
      adequate antiviral therapy.

PMID- 9552226
TI  - The role of the fecal stream in Crohn's disease: an historical and analytic
      review.
AB  - Since 1939, a series of clinical reports and laboratory investigations have
      suggested that the intestinal fecal stream may play a significant part in the
      pathogenesis of Crohn's disease (CD). The beneficial effect of exclusion of the
      stream by ileostomy was followed by improvement in patients with CD of the ileum
      and colon despite little change in the histopathology of the excluded loop, even
      to the point of allowing restoration of intestinal continuity in some patients.
      End ileostomy lowers the risk of recurrence of CD compared with anastomotic
      operations. Ileostomy effluent can reactivate the clinical activity of quiescent
      bypassed bowel and some of its biochemical processes, and may be related to an
      ultrafilterable constituent > 5 microns. Experimental models of inflammatory
      bowel disorders in immunologically altered rodents (transgenic, knockout, or
      spontaneous) require the presence of normal luminal bacteria, especially of the
      Bacteroides species, and respond to antibiotic (metronidazole) therapy. Thus,
      many but not all of the well-recognized clinical features of CD are compatible
      with a pathogenetic role of the fecal stream. Although difficult to quantitate,
      this concept opens the way to a variety of testable research lines, and allows
      some speculation regarding its clinical implications.

PMID- 9552227
TI  - Economic evaluation: an ethical imperative?

PMID- 9552228
TI  - Nutritional therapy in Crohn's disease.
AB  - The value of nutritional support in the prevention and treatment of malnutrition
      in Crohn's disease is undisputed but its role in primary therapy continues to be
      debated. Controlled trials have demonstrated that enteral nutrition induces
      remission rates comparable to that of corticosteroid therapy in Crohn's disease
      and remains the treatment of choice for specific subgroups such as children with
      signs of growth impairment and patients with intolerable steroid-induced side
      effects. The mechanism by which an enteral diet induces remission in Crohn's
      disease is unclear. Bowel rest, reduced antigenic load, nutritional effects, the
      provision of trophic amino acids, modification of gut flora, intestinal
      permeability, or fecal pH have been proposed. Equally, the fat profile of the
      feed may reduce pro-inflammatory ecosanoid synthesis and thus modify disease
      activity. Maintaining long-term remission remains a challenge in the management
      of this disease. Cyclic administration of enteral diets, maintenance drug
      therapy, fat manipulated formulas, or fish oil therapy may be strategies to
      prolong diet-induced remission. In the future, nutrient derivatives that play a
      role in the protective processes of the intestinal mucosa may have application in
      nutritional therapy in Crohn's disease.

PMID- 9552229
TI  - The central role of chemokines (chemotactic cytokines) in the immunopathogenesis
      of ulcerative colitis and Crohn's disease.
AB  - The final composition of leukocytes present in a site of inflammation in response
      to chemokine stimulation and activation may depend on both the nature of the
      secreted chemokines as well as the relative expression of the multitude of
      specific chemokine cell surface receptors on many different cell types. Because
      related receptors with different affinities and cross-reactive binding
      capabilities are present on each type of leukocyte, relative differences in
      receptor distribution and receptor affinity for specific chemokines may
      significantly influence which cells are ultimately attracted to and activated by
      each individual chemokine. Production of IL-8, MCP-1, and ENA-78 by endothelial
      cells, LPMNC, and epithelial cells in IBD could establish a chemotactic gradient
      capable of influencing the increased migration of monocytes/macrophages,
      granulocytes, and lymphocytes from the blood stream through the endothelium into
      both the mucosa and submucosa during chronic IBD. The ability of chemokines to
      induce chemotaxis, leukocyte activation, granule exocytosis, increased production
      of metalloenzymes, and up-regulation of respiratory burst activity indicates that
      there may be a variety of different mechanisms by which chemokines could markedly
      increase chronic inflammation and chronic intestinal tissue destruction in IBD.

PMID- 9552230
TI  - Treatment of erythema nodosum, aphthous stomatitis, and pyoderma gangrenosum in
      patients with IBD.

PMID- 9552231
TI  - How do I treat erythema nodosum, aphthous ulcerations, and pyoderma gangrenosum?

PMID- 9552232
TI  - Treatment of pyoderma gangrenosum, erythema nodosum, and aphthous ulcerations.

PMID- 9552233
TI  - Treatment of extraintestinal manifestations of inflammatory bowel disease.

PMID- 9552267
TI  - Sexual harassment at work. Introduction.
AB  - This article introduces the special section on sexual harassment at work. It
      discusses the importance of sexual harassment as a continuing, chronic
      occupational health psychology problem to which the public health and preventive
      medicine notions of prevention may be applied. The article discusses the dilemmas
      in conducting and reviewing research on harassment, briefly examining some
      alternative methods of inquiry. The three articles in this section are introduced
      and the contrasting legal views of the problems in Europe and the United States
      are addressed. The preventive management of sexual harassment is suggested.

PMID- 9552268
TI  - Personal and organizational predictors of workplace sexual harassment of women by
      men.
AB  - The authors investigated the predictors of workplace sexual harassment in 278
      male university faculty and staff (M age = 45 years). Workplace variables
      (perceptions of organizational sanctions against harassment and perceptions of a
      sexualized workplace) and personal variables (adversarial sexual beliefs, sexual
      harassment beliefs, perspective taking, and self-esteem) were studied as
      predictors of sexualized and gender harassment. Social desirability was
      controlled. Both organizational variables and beliefs about sexual harassment
      predicted gender harassment and sexualized harassment. Perspective taking,
      adversarial sexual beliefs, and sexual harassment beliefs moderated the effects
      of perceived organizational sanctions against harassment on sexualized
      harassment. Findings are discussed as they relate to organizational efforts to
      reduce or prevent sexual harassment.

PMID- 9552269
TI  - Stressors and adverse outcomes for female construction workers.
AB  - The authors examined the impact of a number of job stressors, including sexual
      harassment and gender-based discrimination, on female construction workers' level
      of job satisfaction and psychological and physical health. Results from a
      telephone survey with 211 female laborers indicated that having responsibility
      for others' safety and having support from supervisors and male coworkers was
      related to greater job satisfaction. Increased reported psychological symptoms
      were also related to increased responsibility, as well as skill underutilization,
      experiencing sexual harassment and gender-based discrimination from supervisors
      and coworkers, and having to overcompensate at work. Perceptions of
      overcompensation at work and job uncertainty were positively associated with self
      reports of insomnia. Finally, sexual harassment and gender discrimination were
      positively related to reports of increased nausea and headaches.

PMID- 9552270
TI  - Gender harassment, job satisfaction, and distress among employed white and
      minority women.
AB  - This study tested the hypotheses that gender harassment is related to decreased
      job satisfaction and increased distress, and that White and minority women differ
      in their responses to it, in a sample of 385 women office workers. Over 70%
      reported exposure to gender harassment at work. As predicted, frequency of
      harassment was negatively correlated with job satisfaction and positively
      associated with an index of distress, assessed by self-reported somatic
      complaints, the Center for Epidemiological Studies Depression Scale (L. S.
      Radloff, 1997), and the reported use of alcohol for palliative coping. Minority
      status was unrelated to frequency of reported harassment or to responses to it.
      The tendency to focus on negative aspects of self and environment (negative
      affectivity) was statistically controlled. Findings indicate that gender
      harassment is a commonplace workplace stressor that warrants serious attention.

PMID- 9552271
TI  - Gender, employment, and retirement quality: a life course approach to the
      differential experiences of men and women.
AB  - Using a life course perspective in integrating 2 theories of retirement
      satisfaction--role theory and continuity theory--this study draws on a sample of
      retired men (n = 244) and women (n = 214), ages 50-72, to investigate factors
      contributing to the quality of their retirement experience. Overall, we find that
      men report greater retirement satisfaction than women, although the difference is
      small. For women, increased retirement quality is associated with good health, a
      continuous career (fewer years spent in part-time employment), an early
      retirement (though not earlier than anticipated), and a good postretirement
      income. For men, the key correlates with retirement quality are good health, an
      enjoyable preretirement job, low work-role salience, substantial preretirement
      planning, and retiring for internally motivated reasons (e.g., to do other
      things). These results underscore the importance of a life course focus on
      gendered pathways to and through life transitions such as retirement.

PMID- 9552272
TI  - Temporal architecture of violent incidents.
AB  - Five hundred five reports of violent incidents in British pubs and bars were
      studied by using logical pathway modeling to provide information on the processes
      underlying work-related violence. Logical pathway modeling is innovative in
      examining and mapping sequences in real incidents at a population level. The data
      reveal the most common pathway to be misbehavior by customers, intervention by
      staff (before any physically violent act), physical attack on staff, and injury
      to staff. The data also highlight the likelihood of further action after
      assailants have exited and identify stages in incidents at which most staff and
      customer injuries and damage to property occur. Results assist in the design of
      strategies to reduce the risk from future violence, particularly by training
      staff to recognize and to handle potentially violent situations and to maintain
      vigilance and security following problem incidents.

PMID- 9552273
TI  - An exploration into occupational stress experienced by HIV health care
      professionals who work within genitourinary medicine settings.
AB  - The present study investigates the occupational stress of health care workers
      involved with HIV care in genitourinary medicine (GUM) outpatient departments.
      Sixteen nursing and 14 medical staff completed the P. Gray-Toft and J. G.
      Anderson (1981) occupational stress inventory. This assesses 7 potential sources
      of stress (death and dying, uncertainty regarding treatment, inadequate
      preparation, lack of support, conflict with others, conflict with physicians, and
      workload). The mean scores obtained revealed a preponderance of low-stress scores
      for both medical and nursing staff. Analyses of variance and covariance further
      demonstrated that, in general, levels of stress did not differ within or between
      the occupational groups. However, sources and characteristics of stress were
      different between nurses and doctors. In this group of health care professionals,
      their work with HIV-positive patients within the GUM outpatient setting may be
      instrumental in limiting levels of stress.

PMID- 9552274
TI  - Creating healthier workplaces: The American Psychological Association/National
      Institute of Occupational Safety and Health cooperative agreement. Introduction
      and historical overview.
AB  - This article introduces the special section on the American Psychological
      Association/National Institute for Occupational Safety and Health (APA/NIOSH)
      collaboration. The section includes an overview statement of National Institute
      for Occupational Safety and Health research by Linda Rosenstock and 5
      competitively peer-reviewed articles submitted to the Journal of Occupational
      Health Psychology following their presentation in an earlier form at the 3rd
      APA/NIOSH conference in September 1995. This article provides a brief history of
      the APA/NIOSH collaboration forged at the turn of this decade.

PMID- 9552275
TI  - Work organization research at the National Institute for Occupational Safety and
      Health.
AB  - For 25 years, the National Institute for Occupational Safety and Health (NIOSH)
      has conducted and sponsored laboratory, field, and epidemiological studies that
      have helped define the role of work organization factors in occupational safety
      and health. Research has focused on the health effects of specific job
      conditions, occupational stressors in specific occupations, occupational
      difference in the incidence of stressors and stress-related disorders, and
      intervention strategies. NIOSH and the American Psychological Association have
      formalized the concept of occupational health psychology and developed a
      postdoctoral training program. The National Occupational Research Agenda
      recognizes organization of work as one of 21 national occupational safety and
      health research priority areas. Future research should focus on industries,
      occupations, and populations at special risk; the impact of work organization on
      overall health; the identification of healthy organization characteristics; and
      the development of intervention strategies.

PMID- 9552276
TI  - Employee reactions to ergonomic job design: the moderating effects of health
      locus of control and self-efficacy.
AB  - A field survey of 180 municipal government office employees (82% women, 21-75
      years old) investigated the potential moderating effects of internal health locus
      of control (HLOC) and self-efficacy on employees' reactions to ergonomic job
      design. Internal HLOC moderated the associations between ergonomic job design and
      somatic complaints and turnover intentions, and, to a lesser extent, job
      satisfaction. Self-efficacy moderated the associations between job design and job
      satisfaction, somatic complaints, and, to a lesser extent, persistent pain.
      Employees with low self-efficacy or low internal HLOC were influenced more by
      their physical job conditions than those with high self-efficacy or high internal
      HLOC. Implications for the ergonomic design of offices are discussed.

PMID- 9552277
TI  - Evaluation of a worksite injury and illness prevention program: do the effects of
      the REACH OUT training program reach the employees?
AB  - In this article the authors report the findings of a 2-year study evaluating the
      effectiveness of REACH OUT, a train-the-trainer program developed to assist small
      businesses comply with California legislation, Senate Bill 198 (1989), requiring
      employees to implement a worksite Injury and Illness Prevention Program. Data
      from a case study sample of 8 companies, drawn from 151 Southern California small
      businesses participating in the larger study, are reported. Diagnostic walk
      throughs were performed, and employee surveys collected at the case study
      companies approximately 2 months before the treatment group received the
      intervention and again 1 year later. Results indicate that greater corporate
      compliance led to employees' perceptions of increased health and safety meetings
      and training sessions, which led to greater employee health and safety knowledge
      and improved employee health outcomes.

PMID- 9552278
TI  - Relationships of occupational hazards with burnout: an assessment of measures and
      models.
AB  - A survey of aircraft maintenance technicians with the Canadian Forces (N = 157)
      found support for a model of burnout and occupational risk assessment. The model
      depicted employees' assessment of occupational risk as a function of the
      prevalence and lethalness of workplace hazards, as well as of the amount of
      control employees experience over their interactions with these hazards. A
      confirmatory factor analysis, in which LISREL analysis was used, supported an
      integrated model of risk perception and burnout. In this model, the employee's
      sense of control in managing occupational hazards was pivotal in both the
      experience of exhaustion and being at risk at work. Safety training contributed
      to perceived control and technicians' sense of effectiveness at work. The
      extension of the burnout construct beyond the human service domain was considered
      by using the Maslach Burnout Inventory-General Survey.

PMID- 9552279
TI  - The 120-S minute: using analysis of work activity to prevent psychological
      distress among elementary school teachers.
AB  - Primary school teachers in Quebec suffer psychological distress, as shown by the
      Quebec Health Survey (M. Gervais, 1993; Sante Quebec, 1995). The authors applied
      and extended the French model (F. Guerin, A. Laville, F. Daniellou, J.
      Duraffourg, & A. Kerguelen, 1991) of analysis of work activity to observing
      classroom teaching (14 women in 10 classrooms for a total of 48 hr 24 min) to
      identify stressful elements. The authors observed a rapid sequence of actions,
      eye fixations of short duration, little physical or mental relaxation, multiple
      simultaneous activities, and uncomfortable temperature and humidity levels.
      Teachers use many strategies to teach, to create a learning environment, and to
      maintain attention in classrooms under adverse conditions. Examination of these
      strategies led to recommendations to improve relations between the teachers and
      their supervisors and to make the classroom an easier place to teach.

PMID- 9552280
TI  - Violence at work: personal and organizational outcomes.
AB  - To date, little empirical research has examined the personal and organizational
      outcomes associated with exposure to workplace violence. On the basis of data
      from 194 bank tellers, the authors evaluated, and supported, a model suggesting
      that fear of future violence mediates the relationships between exposure to
      workplace violence and negative outcomes. Specifically, exposure to workplace
      violence predicted fear of future violence that, in turn, predicted psychological
      well-being, somatic symptoms, and intent to leave the organization. These effects
      emerged after controlling for self-report bias. The mediating role of fear was
      supported, and implications for future research and practice are discussed.

PMID- 9552281
TI  - Responses to an in-basket activity: the role of work stress, behavioral control,
      and informational control.
AB  - This study was undertaken to examine the main and interactive effects of work
      stress and work control on levels of adjustment. Work stress, behavioral control,
      and informational control were manipulated in an experimental setting in which
      participants (N = 192) completed an in-basket activity. Although minimal support
      was found for the main and interactive effects of objective work stress,
      behavioral control, and informational control on adjustment, analyses involving
      the subjective measures of these variables revealed strong support for the
      proposal that work stress, behavioral control, and informational control would
      exert main effects on adjustment. There was also evidence that subjective levels
      of behavioral control buffered the negative effects of subjective work stress on
      positive mood, subjective task performance, and task satisfaction.

PMID- 9552282
TI  - Child-care satisfaction: linkages to work attitudes, interrole conflict, and
      maternal separation anxiety.
AB  - Analysis of a 20-item measure of child-care satisfaction (CCS) revealed 3
      interpretable factors: Caregiver Communication, Dependability, and Attentiveness.
      These CCS factors were used, along with employer sensitivity to child-care needs
      and spousal support, in hierarchical multiple regressions to predict various
      measures of work attitudes and role strain. Replicated across 2 samples of
      employed women, the CCS factors demonstrated differential patterns of
      relationships in which Caregiver Attentiveness was associated with lower
      professional-self role conflict and higher levels of affective organizational
      commitment and job satisfaction, whereas Caregiver Communication was associated
      with lower levels of both professional-parent conflict and maternal separation
      anxiety. These findings support the position that CCS is central to the
      functioning of employed mothers in both work and family domains.

PMID- 9552283
TI  - The changing workforce, job stress, and psychological distress.
AB  - The change in the United States from a manufacturing economy to a service economy
      has important implications for theoretical models of the relationships between
      job characteristics and workers' psychological distress. A sample of 600 men and
      women employed full-time were recruited to test 2 theoretical models. The job
      demand-control model posits that jobs that are both high in job demands and low
      in decision latitude are associated with greater psychological distress. The job
      demand-service model posits that jobs that are high in job demands and low in
      service to others are associated with greater psychological distress. Results
      show that the job demand-control model is a significant predictor of
      psychological distress among employees in the manufacturing industry, whereas the
      job demand-service model is a significant predictor of psychological distress
      among employees in the services industries.

PMID- 9552284
TI  - Worker social identity and health-related costs for organizations: a comparative
      study between ethnic groups.
AB  - Health implications of value conflicts at work and 3 coping resources (self
      esteem, collective esteem, and social support at work) were examined for 38
      African American and 64 European American workers. Comparisons indicated that the
      African American participants reported higher levels of value conflicts and
      collective esteem, but lower levels of social support. They also reported more
      health actions (i.e., absenteeism and doctor visits) likely to create
      organizational costs. Value conflicts and the 3 coping resources predicted health
      related behavior. Collective esteem predicted health only for African American
      workers, though social support was a significant predictor only for European
      American workers. The study findings are integrated with existing literature on
      social identity at work, social support, and work influences on health.

PMID- 9552285
TI  - Do resources bolster coping and does coping buffer stress? An organizational
      study with longitudinal aspect and control for negative affectivity.
AB  - Psychiatric workers facing redeployment completed questionnaire measures of
      stressors, resources (locus of control and perceived social support), coping,
      well-being, and negative affectivity, at baseline (N = 109) and 1 year later
      (loss of 7 participants). Regression analyses of the baseline data suggested that
      as stressors increased, so did avoidance coping, but less so for those high in
      internality or perceived social support. Problem-focused coping was bolstered by
      internality and emotion-focused coping by perceived social support. Other
      regression analyses, with a longitudinal aspect, suggested that stressors had a
      deleterious effect on well-being. Problem- and emotion-focused coping had
      beneficial effects, whereas avoidance coping had a (delayed) deleterious effect.
      These effects of coping were predominantly main and not buffering effects.

PMID- 9552286
TI  - A cognitive-affective approach to understanding individual differences in stress
      propensity and resultant strain.
AB  - The cognitive-affective model of the stress response provides a framework for
      making inferences about individual differences in stress propensity and levels of
      resultant strain. A new cognitive-affective conceptualization provides a means of
      analyzing mediating processes affecting psychological and physiological reactions
      to stressors. The model also facilitates examination and understanding of a
      latent cognitive-affective stress propensity construct that moderates the
      relationships between stressors and strain. Propositions are presented with the
      intention of stimulating further research.

PMID- 9552287
TI  - Noise, physiology, and human performance: the potential role of effort.
AB  - Thirty-three male college students ages 18-31 were assigned to 2 levels of noise
      exposure and worked at 2 levels of effort while calculating the Norinder
      arithmetic task (M. Frankenhaeuser & U. Lundberg, 1977). As hypothesized, noise
      increased heart rate, norepinephrine, and cortisol only under high effort. Blood
      pressure did not change significantly. Reaction time slowed significantly under
      noise only when effort was low. Both self-report and epinephrine level confirmed
      the effort manipulation and showed that it was orthogonal to noise levels. These
      data support the adaptive costs hypothesis and have practical implications for
      industry. These implications include trade-offs of productivity and worker
      health, which may be dependent on management style.

PMID- 9552288
TI  - Stressors, locus of control, and social support as consequences of affective
      psychological well-being.
AB  - Tests of the influence of affective psychological well-being on stressors, locus
      of control, and social support in a 1-month follow-up study of 210 male and 34
      female British accountants is reported. There was a marginally significant
      association between the level of psychological symptoms and subsequent reports of
      intensity of quantitative workload stressors. A significant interaction between
      psychological symptoms and a measure of depression-enthusiasm was found to
      predict subsequent locus of control. The results indicate a differential pattern
      of associations between aspects of affective well-being and subsequent reports of
      social support. The results also indicate that initially more frequent stressors
      are associated with subsequently less intense stressors of the same type. The
      findings highlight the dynamic and reciprocal nature of the occupational stress
      process.

PMID- 9552289
TI  - Hostility, social support, and perceptions of work.
AB  - The aim of this study was to determine whether hostility and perceived
      availability of social support are related to perceptions of the work
      environment. The W.W. Cook and D.M. Medley (1954) Hostility (Ho) scale; the
      Interpersonal Support Evaluation List (S. Cohen, R. Mermelstein, T. Kamarck, & H.
      Hoberman, 1985); and measures of collegiality, time pressure, and job
      dissatisfaction were completed by 204 attorneys (159 men and 45 women). After
      controlling for age, gender, and other job characteristics, high Ho scores were
      related to lower perceived supportive collegiality at work. Low perceived
      availability of social support was related to greater job dissatisfaction.
      Neither hostility nor social support was associated with perceptions of time
      pressure at work. These findings suggest that hostility and availability of
      social support may be an important pathway linking certain job characteristics to
      cardiovascular disease and other illnesses.

PMID- 9552290
TI  - Job control and job strain: a test of three models.
AB  - The relationship between job control and job strain is examined. Three models of
      that relationship provide a framework for the study hypotheses: (H1) Control is
      inversely related to job strain, (H2) job demands interact with job control such
      that job strain will be highest when job demands are high and job control is low,
      and (H3) strain increases as the discrepancy between actual and desired levels of
      job control increases. Study participants (N = 316) were health care workers in 2
      hospitals in the northeastern United States. Objective measures of job control
      and job demands were obtained through supervisor evaluations of incumbents' job
      characteristics, and perceptual measures were obtained through incumbents' self
      reports. Results provide support for Hypotheses 1 and 3; little support was found
      for an interaction between job control and job demands.

PMID- 9552292
TI  - Balancing elder care responsibilities and work: two empirical studies.
AB  - It was hypothesized that workers with elder care responsibilities, compared with
      noncaregiving workers, would be more likely to suffer physical symptoms of stress
      and to be absent more days. In Study 1, 67 (32 noncaregivers, 35 caregivers)
      employees of a financial institution were interviewed. In Study 2, 169 (118
      noncaregivers, 51 caregivers) employees of a health care institution completed a
      questionnaire. In Study 1, caregivers were absent more days than noncaregivers,
      and caregiver status was related to the incidence of weight loss or gain,
      drowsiness, and inability to sleep. In Study 2, caregiver status was related to
      the incidence of weight loss or gain, drowsiness, inability to sleep, frequent
      headaches, and nervousness. Caregivers were not significantly different from
      noncaregivers in absenteeism. Results indicate that caregivers' responsibilities
      may negatively affect work performance.

PMID- 9552291
TI  - The role of pleasantness and activation-based well-being in performance
      prediction.
AB  - This study examined the relationships between 2 measures of psychological well
      being and work performance using the circumplex model of emotion as the
      theoretical framework. Although the pleasantness-based measure of well-being
      predicted subsequent work performance, the results failed to establish a
      relationship between the activation-based measure of well-being and work
      performance. Future directions and implications of the findings regarding the
      further refinement of the role of psychological well-being in performance
      prediction are introduced.

PMID- 9552293
TI  - Measuring psychosocial work quality and health: development of health care
      measures of measurement.
AB  - Demands on workload and work efficiency have increased because of ongoing global
      changes in health care organizations. Assessing and evaluating effects of changes
      on organizational and individual well-being require valid and reliable methods.
      Questionnaires from 3 large health care studies were used to develop instruments
      for work quality and health. Variable fields of work quality, health and well
      being, and modifying factors were factor analyzed with replicated structures in
      new samples, including 6 factors of work quality, 5 health factors, and 2
      modifying factors. All except 2 factors had high internal consistency (Cronbach's
      alpha = .69-.84) and low factor intercorrelations within areas. Social climate
      (but not individual resources) had, according to our model, a modifying effect on
      the work-health interaction.

PMID- 9552294
TI  - Dependency and self-criticism as predictors of depression in young doctors.
AB  - Brief measures of depression and of dependency and self-criticism, personality
      factors believed to convey vulnerability to depression, were administered to 318
      medical students. Depression was subsequently measured 2 years later (in the
      highly stressful 1st postgraduate year) and 10 years later when careers were
      established. When initial symptom levels and concurrent workload were controlled,
      dependency and, more particularly, self-criticism were significant predictors of
      depression for male doctors in the 1st postgraduate year. For female doctors,
      self-criticism was the only significant predictor. Ten years later, the
      predictive effects for male doctors were similar, but rather weaker, whereas none
      of the variables predicted depression in female doctors. Implications for
      preventive interventions are discussed.

PMID- 9552295
TI  - The effectiveness and practicality of occupational stress management
      interventions: a survey of subject matter expert opinions.
AB  - Stress management (SM) subject matter experts (SMEs) evaluated 6 widely used
      occupational SM interventions (relaxation, physical fitness, cognitive
      restructuring, meditation, assertiveness training, and stress inoculation) on the
      basis of 10 practicality criteria and 7 effectiveness objectives. Relaxation was
      evaluated overall as the most practical intervention, while meditation and stress
      inoculation were judged as the least practical. Physical fitness was chosen to be
      the most effective intervention, while both meditation and assertiveness training
      were rated overall as the least effective. The findings also revealed that the
      SMEs considered history of success and duration of effect, rather than "relevance
      to program objectives," as the most important factors when selecting SM
      interventions. Incongruence between effectiveness ratings and actual choices of
      interventions are discussed.

PMID- 9552296
TI  - Combined somatic and psychiatric care--effects on personnel treating drug addicts
      with infectious diseases.
AB  - Infectious disease care, psychiatric care of drug addicts, and social care were
      combined in a ward for drug addicts with infectious diseases. The aim of this
      study was to evaluate the effects on the personnel (n = 22). One ward with
      infectious disease care of HIV and AIDS patients (n = 24) and another with
      nonsomatic care of drug addicts (n = 18) were selected to make comparisons
      possible. The questionnaire concerned psychosocial work environment and health.
      The personnel at the new ward also participated in a semistructured interview.
      The personnel at the special ward experienced a significantly higher degree of
      emotional exhaustion and lack of ability to concentrate than the comparison
      groups. They also reported a higher degree of lack of clarity, more job strain,
      and more difficulties due to demands from patients. The combined care is probably
      associated with heavier psychological burdens than other forms of care. In spite
      of this, the personnel experienced their work as meaningful and mentally
      stimulating.

PMID- 9552297
TI  - Effects of work overload and burnout on cholesterol and triglycerides levels: the
      moderating effects of emotional reactivity among male and female employees.
AB  - The effects of objective and subjective overload, and of physical and emotional
      burnout, on cholesterol and triglycerides levels were studied in a
      quasiprospective design. The possible moderating effects of emotional reactivity
      on these relationships were also investigated. The study's hypotheses were tested
      separately for male and female employees. Time 1 (T1) data were collected from
      665 healthy employees (30% women) while they were undergoing periodic health
      examinations in a health-screening center. Time 2 (T2) measures of cholesterol
      and triglycerides were collected 2 to 3 years after T1. The hypotheses were
      tested by regressing each T2 criterion on its T1 level; the control variables of
      age, obesity, diet, alcohol consumption, and smoking; and the other predictors.
      For female employees, the T2-T1 changes in the serum lipids were positively
      predicted by emotional burnout, as expected, but negatively predicted by physical
      fatigue. For male employees, both types of T1 burnout were positive predictors of
      the T2-T1 change in total cholesterol.

PMID- 9552298
TI  - Work characteristics and employee well-being within a context of strategic
      downsizing.
AB  - Findings from this 4-year longitudinal study of strategic downsizing suggest that
      introducing deliberate work organization and change management strategies can
      combat the negative effects of reduced head count. Results showed that there was
      no overall decrease in well-being from before to after downsizing for the 139
      employees remaining in an organization, despite an increase in work demands. The
      potential detrimental effect of demands appears to have been offset by
      improvement in work characteristics arising from initiatives introduced as part
      of the downsizing strategy. This interpretation is consistent with analyses at
      the individual level, which showed that high demands were associated with poorer
      well-being but that increases in control, clarity, and participation were
      associated with improved well-being.

PMID- 9552299
TI  - Responses to occupational hazards: exit and participation.
AB  - The authors developed and tested a model linking subjective risk perceptions to
      both turnover intentions and employees' willingness to participate in health and
      safety programs. On the basis of data from 130 employees of a manufacturing firm,
      the model was supported. Risk perceptions were predicted by employees' accident
      history and perceptions of others' commitment to health and safety. In turn, risk
      perceptions predicted both turnover intentions and willingness to participate.
      These effects emerged after controlling for monomethod bias.

PMID- 9552300
TI  - Factors that influence the use and perceptions of employee assistance programs at
      six worksites.
AB  - Employee assistance programs (EAPs) have gained significant importance in
      contemporary worksites. This article uses data from 6 case studies to examine
      several research questions regarding the relationship between worker demographic
      (e.g., gender, job tenure, and marital status), substance use, and workplace
      policies and the actual and potential use of the company EAP. Unlike in most of
      the existing literature, the authors did not find that gender, marital status, or
      job dissatisfaction are statistically related to actual or potential EAP use at
      most worksites. However, job tenure and some substance use behaviors were related
      to actual EAP use in a positive and statistically significant way. Another
      important finding, underlying the credible integration of EAPs into worksite
      culture, is the positive and robust relationship between employee trust and
      confidence in the EAP and actual use. The results of our study both reinforce
      some long-established principles in the EAP field and encourage further
      consideration of other beliefs.

PMID- 9552301
TI  - Objective measurement of occupational stress factors--an example with San
      Francisco urban transit operators.
AB  - Eighty-one observational work analyses were conducted to measure stressors
      independently of worker appraisal in the San Francisco transit system. On the
      basis of action regulation theory, stress factors were defined as hindrances for
      task performance due to poor work organization or technological design. Stressors
      included (a) work barriers, defined as obstacles that cause extra work or unsafe
      behavior; (b) time pressure; (c) monotonous conditions; and (d) time binding,
      defined as control over timing. Reliability, measured as interrater agreement,
      ranged between 80 and 97%, with kappas of .46-.70. Validity analyses were done
      with 71 transit operators who participated in the observations and 177 operators
      who were assigned mean line-specific observational stressor measures. High odds
      ratios (ORs) were found for barriers and psychosomatic complaints (OR = 3.8, p =
      .00), time pressure and relaxation time needed after work (OR = 3.1, p = .05),
      and barriers and smoking to cope (OR = 3.8, p = .02). Using observational data in
      conjunction with self-report data can reduce confounding and improve
      interpretability of stress and health studies.

PMID- 9552302
TI  - Correspondence of supervisor and subordinate perspectives during major
      organizational change.
AB  - Staff members (N = 2,605) and supervisors (N = 55) of 39 administrative units in
      2 healthcare organizations completed a survey measuring confidence in the
      organization, engagement with their work, and occupational hazards. A
      correlational analysis determined correspondence between the perspectives of
      supervisors with those of staff reporting to them as their facilities adjusted to
      major organizational changes. Supervisors' scores were significantly and
      positively correlated with the corresponding scores of staff members on cynicism,
      meaningfulness, acceptance of change, goals, hospital reputation, and health
      risks. Regression analysis found that relationships were relatively domain
      specific: Supervisor engagement with work was positively related to that of their
      staff members, and supervisors evaluations of the organization were positively
      related to those of their staff members. Supervisor assessment of occupational
      hazards was related to all 3 areas of staff perception.

PMID- 9552303
TI  - Pregnancy planning and the impact on work climate, psychological well-being, and
      work effort in the military.
AB  - This study examined the joint effects of demographics and pregnancy planning and
      timing on work climate, psychological well-being, and work effort among 345
      pregnant U.S. military women from the Army, Navy, Air Force, and Marines. Rank
      predicted both pregnancy planning and career timing. Pregnancy planning was
      positively associated with support from coworkers and supervisors and with
      enhanced work effort and psychological well-being. Pregnancy timing was
      positively associated with support from supervisors, reduced harassment, and
      increased psychological well-being. Rank interacted with the planning and timing
      measures. Junior officers and enlisted participants reported reduced command and
      pregnancy support and increased harassment in conjunction with poorly timed
      pregnancies.

PMID- 9552304
TI  - Novel methods of microparticulate production: application to drug delivery.
AB  - The purpose of this paper is to present two novel techniques, electrostatic
      spraying and oscillating capillary nebulization, for the production of
      microspheres of uniform reproducible particle size distribution. Cholesterol was
      chosen as a model compound to show the utility of both procedures. The processes
      for each method are described, illustrating their simplicity and absence of an
      external detrimental phase. Scanning electron microscopy was used to assess
      morphology while laser diffraction analysis was used to determine particle size.
      Electrostatic spraying of cholesterol yielded particles of round shape, smooth
      surface, and uniform distribution of particle size ranging between 10-30 microns
      and 100-300 microns. Oscillating capillary nebulization of cholesterol molten at
      170 degrees C produced microspheres with an average diameter ranging from 22
      microns to 30 microns when gas back pressures controlling the vibration of the
      capillary ranged from 60 to 90 psi. Electrostatic spraying and oscillating
      capillary nebulization are one-step procedures that result in high production
      yields. Both techniques are easy to set up and afford both production speed and
      reproducibility. The absence of a detrimental external phase makes them
      particularly appealing for the microencapsulation of proteins and polynucleotides
      in polymers with low melting temperatures. The feasibility of production of
      cholesterol microspheres can be extrapolated to the production of excipient-free
      microspheres of steroids.

PMID- 9552305
TI  - Solubility enhancement of a bisnaphthalimide tumoricidal agent, DMP 840, through
      complexation.
AB  - The purpose of this research was to enhance the aqueous solubility of DMP 840 by
      complexation with water-soluble and nontoxic agents, and to understand the nature
      of the interactions involved in complex formation using nuclear magnetic
      resonance (1H-NMR). The solubility of DMP 840 in water, saline, acetate buffers,
      and cosolvent mixtures was determined by high-performance liquid chromatography,
      and the effect of nicotinamide and pyridoxine concentrations on the solubility of
      DMP 840 was examined by the phase solubility method. 1H-NMR spectra were acquired
      in deuterated acetate buffer at 400 MHz on a Varian Unity-400 spectrometer. The
      aqueous solubility of DMP 840 was sensitive to the presence of chloride and
      acetate anions in solution, and did not improve in the presence of cosolvents.
      The use of the nontoxic and water-soluble complex-forming agents nicotinamide and
      pyridoxine, however, resulted in a linear increase in the aqueous solubility of
      DMP 840 with both ligands. The solubilization appears to be due to formation of
      1:1 complexes between DMP 840 and the bioorganic ligands. The complexation
      constants were 15.57 M-1 for the DMP 840:nicotinamide complex and 13.36 M-1 for
      the DMP 840:pyridoxine complex. The NMR results indicate that the interaction is
      a result of vertical or plane-to-plane stacking and the complexation constants
      were in agreement with that obtained by phase solubility. The results suggest
      that the aqueous solubility of a poorly water soluble drug substance such as DMP
      840 can be significantly enhanced by its complexation with water-soluble and
      nontoxic agents.

PMID- 9552306
TI  - Differences in the mechanical strength of dried microcrystalline cellulose
      pellets are not due to significant changes in the degree of hydrogen bonding.
AB  - The mechanical strengths of oven-dried pellets of microcrystalline cellulose,
      MCC, prepared by extruder/marumerizer technology are weaker when ethanol/water
      mixtures are used as granulating solutions than when granulated with water.
      Previously, the difference in the strengths of these pellet systems were thought
      to be due to changes in the degree of hydrogen bonding within these systems. This
      work reports the results of studies using magic-angle-spin nuclear magnetic
      resonance (NMR), x-ray diffraction and degree of crystallinity, and oxygen
      combustion calorimetry studies of various MCC systems developed to test this
      hypothesis. Carbon-13 cross polarization magic-angle spin NMR studies of MCC
      pellets with and without 10% theophylline showed no differences in the spectra of
      these systems. X-ray diffraction studies and heats of combustion data obtained
      from oxygen combustion calorimetry of oven-dried pellets of MCC granulated with
      either water, deuterated water, or a 70/30 ethanol/water mixture were found to
      have no significant differences in their diffraction patterns, degree of
      crystallinity, or internal energies. None of these results provide any evidence
      that a significant net change in the degree of hydrogen bonding is responsible
      for the observed changes in the strengths of these systems. It is hypothesized
      that the strength of these dried pellets may, in part, be due to the conversion
      of some of the intramolecular hydrogen bonded amorphous fibrils at the surface of
      the MCC particles to intermolecular hydrogen bonded fibrils with other MCC
      particles.

PMID- 9552307
TI  - Oramucosal delivery of LHRH: pharmacokinetic studies of controlled and enhanced
      transmucosal permeation.
AB  - Several transmucosal therapeutic systems (TmTs) were developed to study the
      enhanced/controlled delivery of luteinizing hormone-releasing hormone (LHRH)
      through oral mucosae for prolonged periods. TmTs is a track field-shaped bilayer
      mucoadhesive device consisting of fast-release and sustained-release layers. In
      vivo evaluations were performed in beagle dogs, and pharmacokinetic profiles were
      monitored to characterize the transmucosal permeation kinetics of LHRH delivered
      by the various TmTs formulations containing a stabilizer, cetylpyridinium
      chloride, and a permeation enhancer, such as bile salts, to enhance the stability
      and permeability of LHRH. The plasma LHRH concentrations were observed to reach
      the plateau level within 30 min and were maintained for 2 hr following
      application of TmTs, in contrast to a rapid elimination profile observed after IV
      administration. Addition of 5% bile salt into the fast-release layer was observed
      to produce an enhancement in the absorption rate, higher plateau plasma levels,
      and greater systemic bioavailability. Addition of pH modifiers was noted to
      affect the bile salt enhanced transmucosal delivery of LHRH. To prolong the
      plasma LHRH level, several loading doses of LHRH were incorporated into the
      sustained-release layer. The plasma levels were sustained and the area under the
      curve (AUC) values were found to be linearly dependent upon the combined loading
      doses of LHRH in the fast-release and sustained-release layers. Mucosal
      irritation was also measured, using buccal mucosa, and results were observed to
      be low and reversible for the single application. The results indicated that TmTs
      is relatively safe and capable of achieving enhanced and controlled transmucosal
      delivery of peptide drugs.

PMID- 9552308
TI  - Comparison of a respiratory suspension aerosolized by an air-jet and an
      ultrasonic nebulizer.
AB  - In the absence of USP standards and performance monographs, this research sought
      to determine if differences in the aerosolization mechanism (air-jet vs.
      ultrasonic) affected droplet and insoluble particle deposition of a nebulized
      model respiratory suspension. Five milliliters of a model suspension containing
      0.1% w/v fluorescein (to estimate droplet deposition) and known quantities of 1,
      3, and 6 microns latex spheres (representing insoluble drug particles) was
      aerosolized from an air-jet and an ultrasonic nebulizer. Nebulized output was
      collected in a modified Andersen impactor. Samples were analyzed
      spectrophotometrically (490.5 nm) and by a Coulter Counter to estimate droplet
      and sphere deposition, respectively. The distribution of droplets throughout the
      modified impactor for both nebulizers suggested that both the air-jet and the
      ultrasonic nebulizer produced droplets (0.4 to 10 microns in aerodynamic
      diameter) large enough to incorporate 1, 3, and 6 microns insoluble spheres.
      However, Coulter Counter analysis of the sphere distribution revealed that while
      the air-jet nebulized output contained spheres of all sizes, this was not true
      for the ultrasonic nebulizer. In the ultrasonic nebulizer, 99% of the spheres
      (irrespective of size) were not aerosolized and were recovered from the nebulizer
      reservoir at the aerosolization end point. The results highlight the importance
      of evaluating performance of a respiratory suspension in combination with a
      specific nebulizer. When conducting in vitro inertial deposition testing of a
      respiratory suspension, it is inappropriate to assume that deposition trends of
      droplets will predict the deposition of the insoluble dispersed phase.

PMID- 9552309
TI  - The physical state of nafcillin sodium in frozen aqueous solutions and freeze
      dried powders.
AB  - The purpose of this study was to develop a better understanding of the physical
      chemistry of freeze drying of lyotropic liquid crystals using nafcillin sodium as
      a model solute. Solutions and freeze-dried powders of nafcillin sodium were
      studied by polarized light microscopy, differential scanning calorimetry, x-ray
      powder diffraction, and water vapor adsorption. Differential scanning calorimetry
      thermograms of nafcillin sodium solutions contain a melting endotherm at
      approximately -5.5 degrees C and, depending on the concentration and heating
      rate, a crystallization exotherm immediately after this endotherm followed by the
      melting endotherm of ice. When the sample is annealed at -4 degrees C, both the
      endotherm and exotherm are eliminated, and a new endotherm appears at
      approximately -1 degree C on the shoulder of the ice-melting endotherm. The data
      are interpreted as melting of a liquid crystalline phase, followed by
      crystallization. X-ray powder diffractograms of unannealed freeze-dried nafcillin
      sodium are consistent with a lamellar liquid crystal. Diffractograms of annealed
      freeze-dried nafcillin sodium indicate crystalline material which is a different
      crystal form than the monohydrate starting material. Moisture adsorption
      isotherms of the freeze-dried annealed (crystalline) and unannealed (liquid
      crystalline) nafcillin sodium show different affinities for moisture compared to
      the crystalline starting material. Solid-state stability data demonstrate that
      the freeze-dried liquid crystalline form of nafcillin sodium is much less stable
      than the freeze-dried crystal-line material. The literature recognizes two types
      of solute behavior on freezing, where the solute either crystallizes from the
      freeze concentrate or remains amorphous. Lyotropic liquid crystal formation
      during freezing represents a separate category of freezing behavior, the physical
      chemistry of which is worthy of further investigation.

PMID- 9552310
TI  - Evaluation of PLGA microsphere size effect on myotoxicity using the isolated
      rodent skeletal muscle model.
AB  - The present work investigated the magnitude of microsphere-induced acute
      myotoxicity and determined whether this myotoxicity is related to microsphere
      size and/or reconstitution solvent. Using a high molecular weight poly(dl-lactide
      co-glycolide) copolymer, the myotoxicity of two different size microsphere
      formulations (3.6 microns and 19 microns) in normal saline or distilled water was
      quantified using a previously validated isolated rat muscle system. Overall,
      microspheres were found to be relatively nontoxic compared to known myotoxic
      agents (e.g., phenytoin) and control muscles. The smaller microspheres were found
      to be significantly more myotoxic than larger microspheres. Furthermore, the
      myotoxicity was lower in large microspheres reconstituted with normal saline or
      normal saline with 0.5% (w/v) carboxymethylcellulose (to prevent aggregation)
      compared to those reconstituted with distilled water. Smaller microspheres were
      found to be extremely difficult to inject, due to aggregation, which could not be
      prevented by the addition of carboxymethylcellulose. This study suggests that
      larger microspheres are less myotoxic than smaller microspheres.

PMID- 9552311
TI  - Development of a transdermal patch of methadone: in vitro evaluation across
      hairless mouse and human cadaver skin.
AB  - A 3-day monolithic polyacrylate adhesive dispersion type delivery system
      containing methadone was fabricated and in vitro permeation through hairless
      mouse and human cadaver skins was conducted. The effect of skin permeation
      enhancers was also investigated. Skin permeation rate across human cadaver skin
      was found to be lower than that of hairless mouse. Skin permeation profiles
      across both types of skins showed a membrane permeation controlled cumulative
      amount permeated (Q) versus time (t) relationship. Skin permeation rate was found
      to be dependent on both adhesive film thickness and loading dose of the drug in
      the matrix. Effective skin permeation rate across the hairless mouse skin was
      obtained from a patch with 1.5 mm thickness and 15% w/w loading dose. n
      Decylmethyl sulfoxide and Azone were found to produce an effective skin
      permeation rate of methadone through human cadaver skin at a 5% w/w
      concentration. These initial studies demonstrated the feasibility of methadone
      administration through intact skin from a transdermal patch.

PMID- 9552312
TI  - In vitro release of betamethasone dipropionate from petrolatum-based ointments.
AB  - The purpose of this research was to develop new in vitro methodology for
      measuring release from petrolatum-based semisolids and to determine whether two
      ointments, both of which contained betamethasone dipropionate, 0.05%, but with
      different formulations, could be distinguished by release measurements. Several
      receptor media were explored to optimize the procedure utilizing Franz-type
      cells. Analysis was by HPLC. The release slope was 1.5 to 6 times greater from
      the ointment than the "augmented" ointment (which had greater clinical potency).
      Release was highest with a receptor consisting of a 5% solution of hexane in
      acetonitrile. Even so, it was necessary to subject samples of receptor from the
      augmented ointment to evaporation followed by reconstitution with a smaller
      volume of mobile phase to bring corticosteroid concentrations up to quantifiable
      levels. In another series of experiments, the HPLC mobile phase was used as the
      receptor and a relatively large volume (100 microliters) was injected onto the
      column. With the second approach, measured concentrations were lower but more
      reproducible. Quantifiable levels of betamethasone dipropionate were obtained for
      both formulations beginning from the first data point (at 1 hr), with
      satisfactory linearity of plots of amount released per unit area of membrane
      versus the square root of time. Using this methodology, it was possible to
      distinguish the effect of formulation differences in two ointments containing the
      same drug in the same concentration.

PMID- 9552313
TI  - An investigation into the use of thermorheology and texture analysis in the
      evaluation of W/O creams stabilized with a silicone emulsifier.
AB  - The aim of the study was to evaluate a range of W/O semisolid emulsion systems
      (creams) containing white soft paraffin (petrolatum) and a new type of nonionic
      lipophilic silicone emulsifier (Abil EM 90) using a novel combination of
      rheological tests. Emulsifier concentrations from 1.5% to 3.0% w/w were used with
      two manufacturing procedures, cold (25 degrees C) and warm (70 degrees C)
      emulsification, to determine whether and to what extent these variables alter the
      structure and consistency of the creams. The techniques comprised linear
      (continuous flow) and dynamic (oscillatory) rheometry at 25 degrees C, thermal
      flow experiments (from 10 degrees to 90 degrees C and back to 10 degrees C), and
      penetrometry studies. The differences in emulsifier concentration produced
      effects on the rheological properties of the W/ O creams, although the
      manufacturing process was much more influential. Cold emulsification led to
      creams with higher viscosity, lower thixotropy, and better elastic properties.
      The results of penetration tests on creams correlated with those of the
      rheological studies. The flow properties of white soft paraffin at 25 degrees C
      were comparable with the creams obtained by cold emulsification, while the
      elasticity was considerably lower. Thermorheological studies showed evidence for
      transitional behavior for white soft paraffin on heating, but not for the creams.
      White soft paraffin showed a higher viscosity (and resistance to the penetrating
      force) when melted at 70 degrees C and left to solidify at room temperature,
      compared to the "unmelted" sample. This was the opposite trend to that found with
      warm and cold emulsified creams. The input of heat during the emulsification
      process showed a strong effect on the structure and consistency of the W/O creams
      containing petrolatum and silicone emulsifier, resulting in a less viscous
      product. The use of the aforementioned techniques represents a useful and novel
      approach to the evaluation of cream consistency.

PMID- 9552315
TI  - Tuning in society to science and technology.

PMID- 9552314
TI  - Dissolution properties of praziquantel-beta-cyclodextrin systems.
AB  - The purpose of this study was to characterize the dissolution behavior of a
      poorly water-soluble antischistosomal agent, praziquantel (PZQ), from PZQ-beta
      cyclodextrin systems containing 20-100% w/w of drug. Dissolution parameters
      obtained from the release data of simple physical mixtures and inclusion
      compounds prepared by the solvent method were employed to characterize the effect
      of drug loading on the release kinetics of PZQ. All the systems investigated
      showed improved dissolution in comparison with the free drug due to the ability
      to form a complex in solution. The systems prepared by the solvent method showed
      different characteristics and mechanism of dissolution than the physical
      mixtures: At low beta-cyclodextrin (beta-CD) weight fractions (high drug loading)
      their dissolution profiles were higher than those of the physical mixtures. At
      high polymer weight fractions (low drug loading and equimolar ratio) the physical
      mixtures exhibited a 7-fold higher dissolution rate than the pure drug. The
      inclusion systems, on the other hand, showed an improvement in the dissolution
      rate, but to a lesser degree than the physical mixtures. The observed changes in
      the mechanism of release kinetics of the different PZQ-beta-CD systems were
      interpreted using the principles of percolation theory and the results of thermal
      analysis of the physical mixtures and the inclusion compounds.

PMID- 9552316
TI  - Extrusion/spheronization--effect of moisture content and spheronization time on
      pellet characteristics.
AB  - As part of a larger effort aimed at optimizing the properties of pellets produced
      by spheronization of extruded masses, the effect of the moisture content of wet
      masses on extrusion force and torque was studied. The wet masses were composed of
      either microcrystalline cellulose (MCC) or mixtures of MCC with lactose or
      dicalcium phosphate. Based on the force and torque data, a moisture content
      "window" was defined for consistent extrusion. Moisture exerts a lubricant
      effect, and a moisture level of 100-120% w/w dry solid seemed necessary for the
      extrusion of MCC into rod-shaped, discrete pieces. Screen force clearly depended
      on the moisture content but was relatively insensitive to extruder speed,
      especially at 80% and 100% moisture content. The physical properties of pellets
      as a function of spheronization time were studied by sampling the material at
      known intervals. The percent yield, tapped density, and a two-dimensional
      sphericity index of an 18/20 mesh fraction of pellets were measured. Maximum
      yield, tapped density, and sphericity were achieved within 60 sec in the
      spheronizer. With increasing residence time, the shape and density were unchanged
      while the yield was severely reduced. Among the formulations studied, pellets
      with equal amounts of lactose and MCC were superior to those of pure MCC in
      yield, density, and sphericity. Based on these results, an outline to optimize
      the endpoint of the spheronization process for formulations containing MCC is
      suggested.

PMID- 9552317
TI  - Interfacial properties as stability predictors of lecithin-stabilized
      perfluorocarbon emulsions.
AB  - The purpose of this study was to determine whether the addition of small
      quantities of minor lecithin components (phosphatidylinositol, phosphatidic acid,
      lysophosphatidylethanolamine, and cholesterol) and Pluronic F68 to lecithin could
      improve the stability of lecithin-stabilized perfluorocarbon emulsions. Attempts
      were made to correlate emulsion stability with interfacial properties (tension
      and charge). Dynamic interfacial tension was determined using a Teflon Wilhelmy
      plate method [reported previously (1)]. Emulsions were prepared by
      microfluidization. Microelectrophoresis was used to measure emulsion droplet
      charge, and photon correlation spectroscopy and Coulter analysis were used to
      determine emulsion stability as a function of droplet size. Thermal kinetic
      accelerated stability testing was conducted. Various droplet size parameters were
      used to compare emulsion stabilities, and an overall stability ranking, based on
      these parameters, was obtained for each emulsion. Small quantities of additives
      altered emulsion stability and these data were correlated with interfacial
      properties and initial droplet diameters. The addition of cholesterol to lecithin
      resulted in the most stable perfluorocarbon emulsion.

PMID- 9552318
TI  - The role of intra- and extragranular microcrystalline cellulose in tablet
      dissolution.
AB  - The objective of this study was to examine the influence of intra- and
      extragranular microcrystalline cellulose (MCC) on drug dissolution from tablets
      made by high-shear granulation. Granulations were made in a Littleford Model W-10
      B (10-liter) mixer and dried in a fluid bed dryer (Niro Inc.). A Plackett-Burman
      screening design and 2(3) factorial design were employed to study how drug type,
      MCC (intra- or extra-), filler type (lactose or dicalcium phosphate),
      disintegrant type (sodium starch glycolate or croscarmellose sodium) and level,
      proportion of magnesium stearate, and impeller speed affect tablet hardness,
      disintegration time, and dissolution. Two model drugs were chosen based on their
      solubility: metoprolol tartrate (solubility > 1000 mg/ml) and hydrochlorothiazide
      (solubility = 1.05 mg/ml). Tablets were compressed to the same target weight
      (dose) and similar tablet hardness. In some cases, dissolution testing was also
      carried out on the loose granules. The intra-extragranular distribution of MCC
      was found critical to the compactibility and initial dissolution rates from these
      tablets. Intragranular MCC reduced drug dissolution, the effect being most marked
      in the case of the slightly soluble hydrochlorothiazide. For formulations
      containing intragranular MCC, the granulating fluid level on tablet dissolution
      was also important, since an increase in fluid level resulted in slower drug
      dissolution from both the loose granules and the tablets compressed from them.
      Conversely, extragranular MCC tended to increase both dissolution rates and
      compactibility. It may be concluded that the appropriate distribution of MCC
      between and within granules may optimize both dissolution and compactibility
      without changing overall tablet composition.

PMID- 9552319
TI  - In vitro release and permeation of oxytocin from a mucoadhesive buccal patch.
AB  - A biocompatible, mucoadhesive patch was evaluated for potential use in the
      delivery of peptides. The model peptide oxytocin was incorporated into the
      polymeric patch matrix and the diffusion of oxytocin across excised rabbit buccal
      epithelium was studied following patch application. Penetration of oxytocin
      across excised mucosa from an applied patch did not exhibit a characteristic lag
      time for diffusion, with the steady-state flux of oxytocin being 0.062 +/- 0.019
      microgram/cm2/hr. However, when finite-dose diffusion studies were conducted to
      quantitate transport of oxytocin across rabbit buccal mucosa, the mean apparent
      permeability coefficient (P), diffusion coefficient (D), partition coefficient
      (K), and lag time (tlag) were (1.94 +/- 0.74) x 10(-7) cm/sec, (9.20 +/- 1.65) x
      10(-8) cm2/sec, 0.13 +/- 0.05 and 1.86 +/- 0.31 hr, respectively. The release of
      oxytocin from the mucoadhesive buccal patches in vitro proceeded very rapidly
      during the first 2 hr, with 72% of the amount initially incorporated into the
      patches released at 24 hr. The disappearance rate of intact, parent oxytocin when
      an oxytocin solution was placed in direct contact with the serosal and mucosal
      sides of freshly excised rabbit buccal mucosa was 0.74 +/- 0.34 microgram/cm2/hr
      and 3.38 +/- 1.07 micrograms/cm2/hr, respectively. Thus, the buccal patch
      evaluated in these studies appears to be suitable for transmucosal delivery of
      peptides.

PMID- 9552320
TI  - Improvement of the material motion in a rotary processor.
AB  - The purpose of this paper is to reject or to confirm the hypothesis that the
      influence of the water addition rate on the size and size distribution of pellets
      is caused by insufficient spreading of the added water at higher water addition
      rates. To overcome insufficient spreading of the added water, the agitation in
      the rotary processor is intensified by improving the spiral, rope-like movement
      by means of two baffles and a permanent PTFE coating, and by installing a
      chopper. Improvement of the spiral, rope-like movement moderates the influence of
      the water addition rate on the pellet size. The chopper has no significant
      influence on pellet size, pellet size distribution, or percentage of agglomerates
      for the pellets, which are investigated in this study. Furthermore, the
      implementation of the technical modifications does not influence the dissolution
      characteristics of the pellets directly. It is therefore concluded that the water
      added is well spread over the mass by ensuring an optimal spiral, rope-like
      movement, so that incorporation of a chopper is superfluous. The remaining
      influence of the water addition rate on the pellet size can most probably be
      explained by differences in processing time, resulting in different volumes of
      air capable of extracting water from the powder mass.

PMID- 9552321
TI  - Solubility and intrinsic dissolution rate of alprazolam crystal modifications.
AB  - The purpose of the study was to determine the solubility and the intrinsic rates
      of dissolution of three crystal modifications, two anhydrate, and one dihydrate
      of alprazolam, a 1,4-benzodiazepine derivative. Solubility was determined by
      ultraviolet spectrophotometry at different levels of pH, and intrinsic
      dissolution rates were determined by a rotating disk method. The apparent
      solubility of alprazolam crystal modifications was dependent on pH, being 8-10
      mg/ml at pH 1.6 and 0.1 mg/ml at pH 5.0. The apparent solubility values for the
      anhydrate forms were similar, whereas the hydrate form showed lower apparent
      solubility at each pH. The mean intrinsic rates of dissolution for the anhydrate
      forms were 16 and 18 micrograms cm-2 min-1, and for the dihydrate modification 21
      micrograms cm-2 min-1 at 50 rpm, respectively. At 75 rpm, the corresponding
      values were 22, 22, and 27 micrograms cm-2 min-1. The rate of intrinsic
      dissolution was also dependent on the pH. It can be concluded that the apparent
      solubility and the intrinsic dissolution rate of the anhydrate and hydrate forms
      were different. The obtained apparent solubility values at different levels of pH
      for the water-solvated crystal modification were evidently lower than those of
      the two anhydrate forms studied. Furthermore, the intrinsic rate of dissolution
      was significantly (p < 0.05) higher for the hydrate form of alprazolam.

PMID- 9552322
TI  - Influence of tablet hardness and hydrophobicity on the adhesive properties of an
      acrylic resin copolymer.
AB  - The adhesive properties--including the force of adhesion, elongation at adhesive
      failure, the modulus of adhesion, and the adhesive toughness--of an acrylic resin
      copolymer were determined using the butt adhesion technique. Flat-faced tablets
      containing up to 30% hydrogenated castor oil were coated with an aqueous
      dispersion of Eudragit L30D-55. Using data obtained from a Chatillon digital
      force gauge attached to a motorized test stand, force-deflection profiles,
      similar to stress-strain curves generated in the tensile testing of free films,
      were constructed. The surface characteristics of the tablets significantly
      influenced polymer-substrate interaction. The force of adhesion, the elongation
      at adhesive failure, and the adhesive toughness decreased as the surface of the
      tablet became more hydrophobic through the addition of wax to the tablet
      formulation. Lower adhesive properties were found with increasing tablet
      hardness, due to a decrease in the effective area of contact between the film
      coating and the tablet surface. Increased polymer loading resulted in stronger
      adhesion, indicating a relationship between the mechanical and adhesive
      properties of the polymer. The present study demonstrated that the area under the
      force-deflection profile in conjunction with the force of adhesion was more
      representative of the adhesive properties of the polymer.

PMID- 9552323
TI  - Pharmaceutical granulation and tablet formulation using neural networks.
AB  - Current-day pharmaceutical formulation may be trial and error in nature due to
      the absence of a clear relationship between the formulation characteristics
      (output variables) and the material and process variables (input variables).
      Neural networks are networks of adaptable nodes, which through a process of
      learning from task examples, store experiential knowledge and make it available
      for prediction. Prediction of a model granulation and tablet system
      characteristics from the knowledge of material and process variables utilizing
      neural networks is the basis of this presentation. The formulation design
      contained the following variables: granulation equipment, diluent, method of
      binder addition, and the binder concentration. The material, process, granulation
      evaluation, and tablet evaluation data of the formulations were used as the data
      set for training and testing of the neural network models. A comparison of the
      neural network prediction performance with that of regression models was also
      done. Both the granulation model and the tablet model converged fairly rapidly in
      the training step. In the testing step, the predictions for all granulation model
      variables (geometric mean particle size, flow value, bulk density, and tap
      density) were satisfactory. In the tablet model, the predictions for
      disintegration and thickness were also satisfactory. The predictions for hardness
      and friability were less than satisfactory. Two situations where the neural
      network may not perform adequately are discussed. The neural network prediction
      is better or comparable for all the predicted variables in this study compared to
      regression methods. The results clearly show the applicability of neural networks
      to formulation modeling.

PMID- 9552324
TI  - Optima: a windows-based program for computer-aided optimization of controlled
      release dosage forms.
AB  - The purpose of this work was to develop a computer program that assists
      optimization of controlled-release devices, both visually and mathematically,
      using response surface methodology (RSM). A Windows-based computer program,
      Optima, which interactively implemented a number of subroutines for the
      optimization procedure, was developed. Optima is an integrated, user-friendly,
      and graphically oriented program for pharmaceutical dosage form optimization.
      Central composite design is implemented in the program. First- and second-order
      models containing up to five variables can be fitted to the data. The user can
      also choose between linear and exponential individual desirability functions, and
      use them to construct an overall desirability function that combines all the
      response variables in a single response. The program can predict the optimum
      levels of experimental variables, with respect to individual responses and/or the
      overall desirability. Optima has been successfully used in the development of
      sustained-release AZT-loaded microspheres. During the optimization process, three
      experimental variables were investigated and four responses were measured. The
      experimental design was a central composite design that was generated by the
      program. The response values were used by the program to calculate the individual
      desirability functions, which were then combined into an overall desirability
      function. The individual responses as well as the overall desirability function
      were optimized by fitting to a second-order polynomial equation. The response
      surfaces were generated and optimum levels of the experimental variables were
      predicted. The observed responses of the optimized formulation were very close to
      those predicted by Optima. The program proved to be a very useful, integrated
      tool for optimization of the controlled-release microspheres.

PMID- 9552325
TI  - Dual-controlled drug delivery across biodegradable copolymer. I. Delivery
      kinetics of levonorgestrel and estradiol through (caprolactone/lactide) block
      copolymer.
AB  - Four block copolymers of caprolactone (CL) and dl-lactide (LA) with varying
      weight fractions were synthesized by living polymerization in the presence of
      Al/Zn bimetallic alkoxide complex. The solubility of levonorgestrel (LNG) and
      estradiol (E2) in the copolymers was evaluated and found to increase
      exponentially with CL mole fraction. Their aqueous solubilities were also studied
      and observed to increase linearly with the concentration of benzalkonium chloride
      (BAC), a solubilizer. The kinetics of LNG and E2 permeation through the copolymer
      membranes were studied and observed to follow a zero-order kinetics, and the
      permeation rates obtained were noted to be a function of copolymer composition.
      The release kinetics through the copolymer matrix were also studied and noted to
      follow a matrix-diffusion process, and the release flux was found to be dependent
      on copolymer composition. Permeation rates and release fluxes at steady state as
      well as the permeability and solubility of LNG and E2 in the copolymers suggest
      that these permeation parameters are affected by copolymer composition, which
      increase as the CL/LA ratio in the copolymer was increased.

PMID- 9552326
TI  - Interaction of recombinant human bone morphogenetic protein-2 with poly(d,l
      lactide-co-glycolide) microspheres.
AB  - The combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) with
      poly(d,l lactide-co-glycolide) (PLGA) porous microspheres provided for "sustained
      release" of the protein from the microspheres. Soaking 50:50 PLGA microspheres in
      a buffered rhBMP-2 solution for a sufficient period of time to permit equilibrium
      binding enabled quantification of "free" and "bound" protein. "Free" protein is
      defined as protein present within the porous matrix of the microspheres, whereas
      "bound" refers to protein adsorbed to PLGA surfaces. Kinetics of the rhBMP-2
      microsphere association revealed that equilibrium was attained within 8 hr for
      two buffer systems (arginine/histidine, pH 6.50; and glutamic acid/sodium
      glutamate, pH 4.50). Increasing the concentration of the rhBMP-2 stock solution
      used for the interaction studies from 0.025 to 1.0 mg/ml increased the amount of
      rhBMP-2 adsorbed and the concentration of free rhBMP-2. Beyond a 1.0 mg/mL
      concentration, only free rhBMP-2 levels increased. Linearized Langmuir treatment
      of the adsorption data yielded values corresponding to monolayer coverage of the
      microspheres (Cm) and the equilibrium adsorption constant (K) of 0.17
      microgram/cm2 and 7.57 ml/mg, respectively. Studies performed to determine the
      effect of ionic strength revealed that increasing NaCl and buffer concentration
      decreased the amount of protein adsorbed. rhBMP-2 release studies, conducted in
      an isotonic phosphate buffered saline, pH 7.4 vehicle, revealed that free rhBMP-2
      was released during an initial period of 72-96 hr. Following this period, there
      was no discernible release of rhBMP-2 from the microspheres for up to 7 days,
      suggesting that the bound protein would remain at a defect site and release
      slowly upon erosion of the polymer. Mass balances performed by using an
      extraction buffer of high ionic strength confirmed this prediction.

PMID- 9552327
TI  - Studies on the influence of pH and pancreatin on 13C-formaldehyde-induced gelatin
      cross-links using nuclear magnetic resonance.
AB  - Carbon-13 nuclear magnetic resonance (13C-NMR) and 13C-enriched formaldehyde
      (13CH2O) were utilized to observe cross-linking in gelatin. Thus, when a 6%
      solution of gelatin in water was treated with 2000 ppm 13CH2O at 20 degrees C,
      the 15 hr 13C-NMR spectrum of the crosslinked gel showed peaks representing
      carbinolamines (methylols) of arginine and lysine, as well as a peak ascribed to
      a methylene cross-link between arginine and lysine. Similar results were obtained
      when these cross-linking reactions were conducted using only 100 ppm 13CH2O. When
      pancreatin (1% w/v) was added to the solution of 6% gelatin cross-linked with
      2000 ppm 13CH2O, the gel began to revert to a clear fluid solution. After
      incubation for 24 hr at 37 degrees C, the 13C-NMR spectrum of this solution
      confirmed the presence of the methylols of lysine and arginine, and the lysine
      arginine cross-link. When 13CH2O (2000 ppm) was added to a 6% solution of gelatin
      at pH 13.0, the arginine methylol and the lysine-arginine crosslinks were
      produced. The 13CH2O-induced crosslinking of gelatin at pH 2.0, however, yielded
      the lysine methylol as the sole product.

PMID- 9552328
TI  - Micellization and solubilization behavior of sucrose laurate, a new
      pharmaceutical excipient.
AB  - The micellization and solubilization properties of sucrose laurate have been
      investigated. Solubilization experiments showed that numerous poorly water
      soluble drug substances could be solubilized by aqueous sucrose laurate
      solutions; the solubilization was uncomplicated and the maximum solubilizate
      concentration was high. Laser light scattering investigations proved that
      solutions containing pure sucrose monolaurate formed spheroidally shaped micelles
      with a hydrodynamic radius of 29.2 A, which behaved like ideal particles, showing
      no solute-solute interactions. Surprisingly, the hydrodynamic radii of the
      sucrose monolaurate micelles were hardly changed by the introduction of 0.20%
      cyclosporin-A. The addition of sucrose dilaurate, the main impurity of the
      sucrose laurate product, however, resulted in large and polydisperse structures.
      Considering the critical packing parameters, the light scattering results could
      be explained by assuming a transformation of the spherical micelle into a disk
      with rounded edge.

PMID- 9552329
TI  - Drug release from a multiparticulate pellet system.
AB  - Multiparticulate pellet systems are used as both immediate and modified release
      dosage forms. Previous work has classified uncoated pellet systems prepared from
      microcrystalline cellulose as an inert matrix. The Higuchi square root of time
      equation, derived to describe drug release from a single planar system, is the
      accepted method to evaluate drug release from both planar and spherical
      heterogeneous inert granular matrices. A second equation of interest, the Higuchi
      cubic equation, was derived to describe drug release from a spherical pellet.
      Both equations predict a linear relationship between drug release and the square
      root of time or time. The purpose of the present study was to evaluate drug
      release from a multiparticulate pellet system using both equations and to study
      any differences when both equations are used to describe the same drug release
      data. By evaluating dissolution data from various pellet mesh cuts representing
      different bead radii and surface areas, changes in the slopes of both plots would
      be expected. Pellets were manufactured using extrusion/spheronization technology
      and consisted of 90% microcrystalline cellulose and 10% acetaminophen.
      Statistical comparison indicates that the Higuchi cubic equation seems to be more
      sensitive to changes in pellet size. While the square root of time equation
      describes the drug release data from granular, inert, spherical pellets, it may
      be better to utilize the Higuchi cubic equation because it is more sensitive to
      changes in particle size.

PMID- 9552330
TI  - The impact of crystallinity on Brequinar sodium hygroscopicity.
AB  - The hygroscopicity of Brequinar sodium, an organ transplant immunosuppressant, at
      75% relative humidity highly depends on the crystal form or crystallinity of the
      drug substance. Hygroscopicity and ease of water uptake of three lots of
      Brequinar sodium were investigated. Those lots contained different impurities at
      levels ranging from 0.26% to 0.5%. DSC thermograms of the hydrated samples
      suggest that unbound/loosely bound water was released around 90 degrees C and
      water of hydration was released at 175 degrees C. At equilibrium, 2% of the water
      was tightly bound. Stoichiometry suggests that this is a hemihydrate.
      Unbound/loosely bound water has no impact on the hemihydrate crystal structure as
      indicated by x-ray powder diffraction patterns. The results suggest that the less
      perfect crystals exhibited a faster water uptake and converted to a stable
      hemihydrate when stored at 75% relative humidity. Both the anhydrous and the
      hemihydrate forms of Brequinar sodium exhibited rapid dissolution rate and
      comparable water solubility.

PMID- 9552331
TI  - Development and optimization of a solid dispersion hot-melt fluid bed coating
      method.
AB  - A new hot-melt fluid bed coating process has been developed, characterized, and
      optimized. Polyethylene glycol served as the model coating agent and was charged
      with substrate into the fluid bed chamber in the solid state. The processing
      stages included: (A) warm-up, (B) preheating, (C) melting-spreading, and (D)
      cooling-congealing. A central composite design was utilized to characterize and
      optimize the process. Substrate porosity and density evaluations were conducted
      by mercury intrusion. The method proved capable of coating nonpareils from 10 to
      35 mesh (0.500 to 2.00 mm) and tablets up to 1 g. The nonpareils were coated as
      individual particles, while particle sizes significantly smaller than 40 mesh
      (0.420 mm) tended to agglomerate. The porosity and density values of dissimilar
      nonpareil batches showed a large degree of variation, affecting the method's
      reproducibility. Additive coatings were achieved by sequential runs using coating
      agents of diminishing melting points. The method is a viable alternative to hot
      melt spray-coating processes. Organic solvents, spraying equipment, steam
      jackets, and/or heating tape are eliminated from the process.

PMID- 9552332
TI  - Novel technology for the preparation of sterile alginate-poly-l-lysine
      microcapsules in a bioreactor.
AB  - The purpose of this study was to develop a method that may be suitable for the
      commercial manufacture of sterile alginate-polylysine-alginate microcapsules in a
      bioreactor. A Turbotak atomizing device in conjunction with a Bellco Bioreactor
      was used to prepare sterile microcapsules. Aseptic procedures were followed using
      sterilized equipment and materials. Sodium alginate solution was sprayed into
      calcium chloride solution using the Turbotak, with nitrogen as the atomizing gas.
      The resultant gelled alginate microcapsules were coated with polylysine and
      alginate to produce alginate-poly-l-lysine microcapsules. In-process
      contamination of the atomizing gas and microcapsules was investigated using
      modified USP sterility tests. Microcapsule size was determined using a light
      blockage technique (Accusizer) which measures both number and volume weighted
      mean diameters. The microcapsules prepared passed a modified USP sterility test,
      and the Bellco Bioreactor was found to minimize the possibilities of
      environmental contamination and therefore enhanced operator safety. The flow rate
      of the atomizing gas was determined to significantly alter number and volume
      weighted mean microcapsule diameters. Statistical analysis indicated that the
      number weighted mean diameters in conjunction with the volume weighted mean
      diameters can be used to detect batch-to-batch changes in microcapsule diameters.
      In conclusion, the modified Bellco Bioreactor offers a novel approach for
      producing sterile alginate-polylysine microcapsules on a laboratory scale.

PMID- 9552334
TI  - Determination of intraparticulate mass transfer coefficients via permeation
      measurements: theory and experimental validation.
AB  - A mathematical model of mass transfer through a heterogeneous, multiphase barrier
      has been developed where the dispersed phase is capable of uptake of the
      diffusant according to a linear relationship. The model was used to describe the
      penetration of drugs through dispersions of permeable globules in media of known
      diffusional properties. Water-in-oil-in-water (W/O/W) multiple emulsions have
      been studied by this method. When used to analyze data obtained with a simple
      diffusion cell, the model allows the calculation of the mass transfer coefficient
      which characterizes the diffusional mass transfer across oil-water interfaces
      within the emulsions. The mass transfer coefficient is directly related to the
      drug release rate from the internal phases of multiple emulsions. Those cases
      where instantaneous equilibria are established or where impermeable globules are
      present can be treated as special limiting cases. Differential equations which
      express diffusant concentrations as functions of time, space, and dispersion
      system parameters have been solved by Laplace transformation without recourse to
      numerical methods. The values of the mass transfer coefficient are shown to
      reflect the physical characteristics of multiple emulsion systems.

PMID- 9552333
TI  - Validation of cleaning procedures for highly potent drugs. I. Losoxantrone.
AB  - The validation of a procedure designed to clean glass and stainless steel
      surfaces after exposure to the experimental anticancer drug losoxantrone is
      described. The cleaning procedure, using water and hypochlorite bleach, was
      validated using a wipe test and a high-performance liquid chromatography (HPLC)
      method developed to quantitate low levels of losoxantrone. The HPLC method is
      shown to be linear and reproducible (relative standard deviation (RSD): 7.1% or
      less), with a detection limit of 2 ng/ml. Recoveries of 71.0%, 50.1%, and 57.6%
      were reproducibly obtained from the wipe pads, glass plates, and stainless steel
      plates, respectively, at levels of 70-140 ng per 100 cm2. The cleaning procedure
      is shown to clean glass and stainless steel plates to less than 20 ng and 17 ng
      losoxantrone per 100 cm2, respectively. These results demonstrate the need to
      fully characterize the recovery of drugs from surfaces and swabs in order to
      properly validate cleaning procedures.

PMID- 9552335
TI  - Determination of the pKa and pH-solubility behavior of an ionizable cyclic
      carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4- (trifluoromethyl)
      2H-3,1-benzoxazin-2-one (DMP 266).
AB  - The solubility of a nonnucleoside reverse transcriptase inhibitor, (S)-6-chloro-4
      (cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl )- 2H-3,1-benzoxazin-2-one
      (DMP 266), was investigated as a function of pH. A dramatic increase in the
      aqueous solubility was observed at pH > or = 10, which was consistent with going
      from a neutral to a charged species. The ionization of the proton positioned on
      the carbamate functionality was confirmed spectrophotometrically (pKa = 10.1).
      The spectrophotometric result was in excellent agreement with that obtained from
      the solubility studies (pKa = 10.2). The ionization behavior of DMP 266
      represents a unique case in which the pKa for a carbamate functional group is
      quite low. The anomalous pKa value may be attributed to stabilization of the
      negatively charged species through inductive effects, which originate from the
      surrounding substituents and delocalization of the negative charge via resonance
      effects.

PMID- 9552336
TI  - Sequential statistical optimization of a positively-charged submicron emulsion of
      miconazole.
AB  - A positively charged oil/water (O/W) emulsion containing an antifungal agent was
      developed for ophthalmic use. An attempt was made using a sequential statistical
      methodology to optimize the O/W emulsion by varying both formulation and process
      parameters to obtain the smallest droplet size emulsion that can remain stable
      for a long period of time. During the first step of the study, not less than 7
      parameters were found to be important--drug content, amount of lipophilic phase,
      poloxamer concentration, quantity of the phospholipids-stearylamine couple, pH
      adjustment, time of coarse emulsification and time of high pressure
      homogenization. A screening approach based on Hadamard's matrix was used to
      select the parameters displaying the most significant effects on response
      parameters. A first set of 8 experiments proved efficient enough to define the
      concentration of poloxamer and the quantity of the couple phospholipids
      stearylamine, which confer the overall positive charge to the emulsified droplet,
      as the most significant parameters affecting the final droplet size of the
      emulsions formed. A 2k-type experimental design was then built with the two main
      factors in order to evaluate a first-order polynomial model with interaction.
      Poor analysis of variance results after an additional center experiment was
      performed revealed the lack of fit of the linear model as well as the importance
      of the response surface curvature due to a close optimum location. To find the
      optimal operating conditions the design was sequentially completed with 4 more
      experiments according to the Box and Wilson method. The response surfaces in 3
      dimensional representation and their corresponding contour plots proved helpful
      in analyzing the validated models and in highlighting the precise optimum
      location. The optimized positive submicron emulsion is now under in vivo
      investigation.

PMID- 9552337
TI  - Blending validation of low drug content dosage forms.

PMID- 9552338
TI  - Compaction simulator studies of a new drug substance: effect of particle size and
      shape, and its binary mixtures with microcrystalline cellulose.
AB  - The compaction characteristics of a new drug substance with two crystal habits
      and particle size fractions as well as its binary mixtures with microcrystalline
      cellulose were studied using an integrated compaction research system under 300
      and 450 MPa pressures. The results indicate that the drug substance has poor
      intrinsic compaction properties. The three-dimensional hexagonal crystal habit or
      smaller particle size consistently produced a slightly higher total work of
      compaction as compared with the cubic brick habit or larger particle size,
      respectively. However, neither crystal habit produced a coherent compact. The
      compactability of the drug substance was improved by the inclusion of
      microcrystalline cellulose, and the crushing strength of the compacts increased
      as the amount of microcrystalline cellulose in the binary mixture was increased.
      Such correlation was not observed when the compaction data were evaluated using
      either the Heckel equation or the percentage porosity change as a function of
      applied pressure.

PMID- 9552339
TI  - beta-D(+) glucose-glucose oxidase-catalase for use as an antioxidant system.
AB  - The purpose of this study was to investigate the use of beta-D(+) glucose-glucose
      oxidase (EC 1.1.3.4)-catalase (EC 1.11.1.6) (BDG-GO-CAT) as a new antioxidant
      system in solutions. A novel method for estimation of activity of the system was
      developed using a dissolved oxygen (DO) meter and an oxygen probe. The method can
      be used to determine the enzymatic activity of the system at GO concentrations of
      0.005 to 0.030 unit/ml, with an r2 of 0.995 for the linearity of the standard
      curve, and can be adapted for analysis in any solution. At room temperature of
      23.0 degrees +/- 2.0 degrees C, the maximum activity of the BDG-GO-CAT system was
      found to occur at pH 5.40. The half-life values for the stability of GO-CAT in
      0.10 M phosphate buffer solutions of pH 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, and 10.0
      were 9.78, 49.43, 53.46, 36.51, 12.68, 1.84, and 0.80 weeks, respectively.
      Dextrose was used in place of beta-D(+) glucose for cost-saving purposes, and a
      standard curve for the activity of GO-CAT was obtained using 20 mg/ml dextrose.
      The BDG-GO-CAT was effective as a DO-scavenger in closed containers, when the
      containers were opened and exposed to atmosphere for 2 days between tests, and
      upon reclosing them. Pharmaceutical excipients such as ethanol, glycerin,
      propylene glycol, methylparaben, propylparaben, artificial strawberry flavor, and
      sodium benzoate did not show any adverse effect on the activity of BDG-GO-CAT.
      Sorbitol, high-fructose corn syrup, sucrose, and polyethylene glycol 3350
      increased the rate of DO removal. Sodium carboxymethyl-cellulose (CMC) at 2.0%
      w/v decreased the rate of DO removal. These studies indicate that the
      BDG(dextrose)-GO-CAT system warrants serious consideration for use an antioxidant
      system in aqueous formulations.

PMID- 9552341
TI  - Positively charged self-emulsifying oil formulation for improving oral
      bioavailability of progesterone.
AB  - A self-emulsifying oil formulation (SEOF) comprised of Tween 80, benzyl alcohol
      (BA), ethyl oleate (EO), and oleylamine (OA), able to produce positively charged
      submicron emulsions upon aqueous or buffer dilution, was developed and
      characterized. The positive charge of the formulation was attributed to the
      localization of the cationic lipid, OA, at the oil/water interface of the diluted
      SEOFs. Binary phase diagram analysis of the basic lipophilic system showed that
      the SEOF elicited progressive inverse phase behavior under continuous aqueous
      phase dilution. At infinite dilution fine submicron o/w emulsions were formed
      only when BA concentrations did not exceed 50% in the formulation. The self
      emulsification process was not markedly affected by the variation in pH over the
      entire physiological range. The neurotoxic effects observed in acute toxicity
      studies with the concentrated emulsion containing 3% BA obtained from the
      dilution of the SEOF vehicle were attributed to the BA since a simple aqueous
      solution at the same BA dose caused similar adverse effects. However, no toxic
      effects were noticed when the dose administered was 30 times the potential dose
      that could probably be administered to humans. Comparative oral bioavailability
      studies in young female rats using several different liquid dosage forms of
      progesterone indicated that of those studied, only the positively charged SEOF
      could be considered a potential effective dosage form for oral administration of
      progesterone since it elicited the highest and most satisfactory absorption
      profile.

PMID- 9552340
TI  - In vitro permeation study of a mucoadhesive drug delivery system for controlled
      delivery of nonoxynol-9.
AB  - A carbopol 934P-based drug delivery system (AmDDS) was developed to achieve the
      dual-controlled delivery of Nonoxynol-9 (N-9), a spermicidal agent, and EDTA, a
      potentiator of spermicidal activity. This gel-type system made intimate contact
      with vaginal mucosa and maintained an effective drug concentration within the
      vagina for a prolonged period of time. An existing mathematical model, based on a
      unilayer diffusion membrane, was applied for describing permeation of N-9 through
      vaginal mucosa. Vaginal permeation of N-9 from AmDDS was negligible over the
      initial 5 hr, then increased in a Q versus t pattern, but remained low. A
      relationship was observed between the permeation rate (Js) of drug through
      vaginal mucosa and the release flux (Q/t1/2) from AmDDS, which showed that the
      permeation rate (Js) increased with increased square of the release flux
      [(Q/t1/2)2] in a hyperbolic manner. This result indicated that release of N-9
      from AmDDS is still the rate-limiting step at doses within the tested range.
      EDTA, at concentration of up to 0.32%, did not change the permeation rate of N-9
      through vaginal mucosa. It is thus concluded that the developed AmDDS can control
      the intravaginal delivery of N-9 as well as its permeation through vaginal
      mucosa.

PMID- 9552342
TI  - Dissolution enhancement of an insoluble drug by physical mixture with a
      superdisintegrant: optimization with a simplex lattice design.
AB  - The aim of the present work was to optimize a tablet formulation containing a
      physical mixture of a practically insoluble drug (prednisone) with a
      superdisintegrant (croscarmellose sodium) and two filler-binders characterized by
      differing water solubility (dicalcium phosphate dihydrate and anhydrous beta
      lactose). Crushing strength, disintegration, and dissolution were measured for 10
      formulations distributed over a factor space according to a simplex lattice
      design for a special cubic model. Multiple linear regression analysis was used to
      assess the best fit for each variable. The model predicted that increasing the
      amount of disintegrant to a critical amount (50%) would result in reduced
      disintegration time for dicalcium phosphate/beta-lactose ratios > 0.3, no changes
      in disintegration time for ratios < 0.3, and for all ratios an improvement in
      dissolution at 10 min. Crushing strength values of dicalcium phosphate increased
      with increasing disintegration concentration but not for beta-lactose tablets.
      The physical mixture of a practically insoluble drug with a superdisintegrant was
      confirmed as a valid approach to the improvement of dissolution, even in presence
      of other components. The solubility of the filler-binders influenced the minimum
      amount of disintegrant needed; when a soluble diluent was used, the amount of
      disintegrant required was reduced.

PMID- 9552343
TI  - The evaluation of lyophilized polymer matrices for administering recombinant
      human bone morphogenetic protein-2.
AB  - Novel unitary devices, prepared by lyophilization of viscous solutions of sodium
      carboxymethylcellulose (CMC) and methylcellulose (MC), were evaluated as
      sustained-release delivery systems for recombinant human bone morphogenetic
      protein-2 (rhBMP-2). In vitro characterization of the unitary devices, which
      contained rhBMP-2-loaded poly (d,l lactide-co-glycolide) (PLGA) bioerodible
      particles (BEPs), was conducted over a 2-month period. Determinations included
      buffer uptake, mass and molecular weight loss and rhBMP-2 release from the
      unitary devices. CMC devices imbibed approximately 16 times their weight of
      buffer, while with MC, equilibrium uptake was approximately 6 times the dry
      weight of the devices. Overall mass loss percentages were approximately 55 and
      35%, respectively, for CMC and MC devices. rhBMP-2 release from the devices was
      essentially a triphasic process: an initial phase during which "free" protein
      (rhBMP-2 present on the surface and within the pores of the PLGA BEPs) was
      released, a lag period during which no release was discerned, and then release of
      "bound" rhBMP-2 (protein adsorbed to the BEPs). The release of bound protein
      correlated with the mass loss of the polymer which began after 3 weeks. Release
      from the unitary devices was lower than that from the BEPs alone, due to a
      retardation effect of the gelled CMC/MC polymers. In rabbits in which full
      thickness cranial bone defects were created, the implants were well tolerated and
      induced significant new bone growth during an 8-week evaluation period. The CMC
      devices appear to have induced bone earlier (at 2 weeks), but this did not affect
      eventual 8-week results. CMC devices without rhBMP-2 appeared to provide some
      bone conduction, in contrast to the blank MC devices.

PMID- 9552344
TI  - Phenytoin sodium microcapsules: bench scale formulation, process characterization
      and release kinetics.
AB  - The objective of this investigation was to formulate and prepare sustained-action
      microcapsules of phenytoin sodium (diphenyl hydantoin sodium salt). Using
      ethylcellulose and methyl acrylic acid copolymers (Eudragit S-100 and L-100) as
      coating materials, microcapsules of phenytoin sodium were formulated by an
      organic phase separation and a granule coating method. The phase diagrams were
      used to study the phase separation in an ethylcellulose-petroleum ether-toluene
      system, and the effect of temperature and amount of petroleum ether on the
      ethylcellulose left in the organic solvent mixture was investigated. The phase
      diagrams showed that increase in temperature did not significantly affect the
      ethylcellulose residue, and 60 ml of nonsolvent was found adequate for
      microencapsulation. In vitro release of the formulated microcapsules and the
      commercially available preparations was performed in CO2-free distilled water
      using the USP XXIII rotating basket method, and the profiles were evaluated by
      Higuchi kinetics. Geometric mean diameters of the microparticles prepared by two
      different methods showed differences due to different core:wall ratios. A 4 x 5
      factorial design was utilized and multiple regression was applied to the
      dependent variables (ethylcellulose content, percent dissolved) against the
      independent variables (amount of nonsolvent, temperature, core:wall ratio); the
      optimum phenytoin sodium-to-ethylcellulose ratio was 1:2.3. Utilizing second
      order polynomial equations, response-surface graphs and contour plots pointed out
      the time necessary for 40%, 55%, and 70% release of phenytoin sodium. The desired
      release profiles were obtained with formulations E-5, ES-2 and ESL-2.

PMID- 9552345
TI  - Insoluble collagen matrices for prolonged delivery of proteins.
AB  - The purpose of this investigation was to evaluate the application of high
      molecular weight, insoluble collagen as a carrier material for proteins. Matrices
      were formulated and their behavior in buffer solution was investigated with focus
      on swelling and inner structure. Cross-linking with glutaraldehyde was introduced
      prior to the formation of the devices and its influence characterized. In
      addition, the enzymatic degradation process was studied and release experiments
      with systems loaded with fluorescent-labeled bovine serum albumin were carried
      out. Insoluble collagen matrices were characterized by intensive swelling in
      buffer resulting in development of a coarse porous character. Cross-linking
      strongly reduced the water penetration, leading to denser structures of the
      swollen devices. The continuous enzymatic degradation of the disk-shaped matrices
      by collagenase followed the kinetics of an heterogeneous enzymatic process with
      hindrance of proteolysis by the addition of glutaraldehyde. Release studies
      demonstrated that large amounts of model protein were held in the matrices with
      increased cross-linking degree. In presence of collagenase a prolonged release of
      the trapped protein over several days by matrix cleavage could be achieved.
      Insoluble collagen can be effective as a carrier material for proteins with an in
      vitro release characteristic by both diffusion-controlled and enzymatic
      degradation mechanisms. Cross-linking at the stage of preparing the aqueous
      dispersion offers an alternative to subsequent cross-linking processes.

PMID- 9552346
TI  - Water-solid interactions. III. Effect of glass transition temperature, Tg, and
      processing on tensile strength of compacts of lactose and lactose/polyvinyl
      pyrrolidone.
AB  - The effect of moisture sorption at different relative humidities on the tensile
      strength and the physical stability of compacts of crystalline and partly
      amorphous lactose, alone and in binary mixtures with PVP, has been studied.
      Furthermore, the role of moisture as a plasticizer and its effect on the glass
      transition temperature, Tg, are related to the compactibiltiy. Samples were
      conditioned for 2 hr using a climate test chamber at different relative
      humidities. Moisture sorption was determined, the radial crushing strength for
      compacts was measured immediately and after storage, and the tensile strength was
      calculated. The glass transition temperature, Tg, was determined using DSC. The
      tensile strength of the compacts was found to depend on both the conditioning
      humidity and the humidity during storage. An increase in humidity to a level at
      which the glass transition temperature, Tg, fell below the operating temperature,
      T, resulted in transition from a rigid glassy state to a mobile rubbery state.
      For compacts of partly amorphous lactose, an increase in the tensile strength was
      observed during storage of tablets, due to recrystallization of the amorphous
      regions above Tg. Tablets of mixtures of lactose and PVP exhibit a sharp decrease
      in tensile strength at humidities above 70% RH, due to the glass-to-rubber
      transition of PVP.

PMID- 9552347
TI  - Dilution potential: a new perspective.
AB  - The objective of this work was to develop a method to assess the dilution
      capacity of direct compression excipients based on a technique previously
      proposed by Minchom and Armstrong (MA). The technique involves the addition of
      increasing quantities of a poorly compactible (compressible) material to the
      excipient and measuring the resultant decrease in the AUC of the tensile strength
      versus compaction force profiles. The AUC of each mixture is divided by the AUC
      of the "0% mixture" to obtain MA's "work potential," called "area ratios" in the
      present study. The applicability of this approach was tested using three
      excipients differing in their deformation mechanisms: microcrystalline cellulose
      (Avicel PH 101, 102, 200, 301, 302) representing a plastic material; dibasic
      calcium phosphate (Cal-Star) representing a brittle material, and anhydrous
      lactose, which exhibits both brittle and plastic properties. Ascorbic acid or
      acetaminophen was the poorly compactible challenge material. In the first study,
      the MA method was found to apply only to Avicel PH 101, since the area ratios for
      mixtures containing different compositions of acetaminophen with either Cal-Star
      or anhydrous lactose remain constant until a certain percentage of drug is
      exceeded, after which a decline starts to be observed. Further work carried out
      on mixtures of different grades of Avicel with ascorbic acid revealed that MA's
      approach reflects only the ability of the excipient to handle internal stress
      induced by the drug and does not take into account the intrinsic ability of the
      drug-free excipient to form strong compacts. A new index was thus proposed,
      called the dilution capacity index (DCI), which weights the MA index by the AUC
      of the drug-free excipient. The results suggest that DCI can be used to compare
      different grades of microcrystalline cellulose and provide in-house quality
      control for microcrystalline cellulose suppliers.

PMID- 9552348
TI  - Mechanical properties of single pellets containing acrylic polymers.
AB  - Three aqueous-based acrylic latex dispersions, Eudragit L 30 D, NE 30 D, and RS
      30 D, were incorporated as granulating binders into a powder blend of
      microcrystalline cellulose and anhydrous lactose by wet massing. Spheronized
      pellets were prepared by extrusion-spheronization and the mechanical properties
      of single pellets, including the tensile strength at break and the Young's
      modulus were determined from the stress-strain profiles using a Chatillon TCD-200
      tension/compression digital test gauge. The influence of particle size and
      plasticizer on the mechanical properties of pellets containing Eudragit RS 30 D
      was investigated. All bead formulations deformed by brittle fracture under a
      diametral compression force. The mechanical strength was found to be influenced
      by the adhesive strength between the polymers and the powder particles instead of
      the cohesive strength of each polymer. The Young's modulus and the tensile
      strength were also significantly influenced by the type and concentration of
      polymer, the presence of plasticizer, and the particle size of the beads. The
      results were related to the properties of the polymers and the fracture
      mechanisms of the beads. Furthermore, the polymer type and the incorporation of
      plasticizer influenced the susceptibility of the moistened extruded granules to
      the shearing forces during the spheronization process, which influenced the
      surface morphological properties of the pellets.

PMID- 9552349
TI  - Checkpoints in the cell cycle from a modeler's perspective.
AB  - The cell division cycle is a complex process by which cells grow and divide into
      two viable daughter cells. So that mistakes are not made in this crucial
      replication process, cells stop at one or more "checkpoints" in the cycle to
      query their internal state and external conditions, before proceeding to the next
      stage of the cycle. In this paper we study some simple mathematical models of
      cell cycle arrest in G1 ("Start") and G2. Our models help to relate the molecular
      mechanisms of these checkpoints with physiological properties of the cell cycle.

PMID- 9552350
TI  - The role of RB in cell cycle control.
AB  - The retinoblastoma protein is an inhibitor of cell cycle progression from the G1
      to the S phase of the cell cycle. It acts through its ability to interact with
      cellular target molecules such as E2F transcription factors. The function of pRB
      is negatively regulated by a cell-cycle dependent phosphorylation catalyzed by
      cyclin-dependent kinases in the late G1 cell cycle phase. Recent evidence
      indicates that this pRB inactivation is a key molecular event leading to the S
      phase commitment at the G1 restriction point in the cell cycle. Deregulated
      inactivation of pRB in G1 phase may be a universal mechanism underlying cellular
      transformation.

PMID- 9552351
TI  - Regulation of p70s6k/p85s6k and its role in the cell cycle.
AB  - Two to three-fold increases in the rate of protein synthesis are required both to
      enter the G1 phase of the cell cycle from G0 and to proceed to S phase in
      response to growth factors and mitogens. This increase is in part regulated via
      multiple phosphorylation of the 40S ribosomal protein S6 by the mitogen
      stimulated p70s6k/p85s6k. At the protein synthesis level this event appears to be
      involved in specifically increasing the efficiency of translation of a family of
      essential mRNAs containing a polypyrimidine tract at their 5' transcriptional
      start site. The activation of p70s6k/p85s6k and maintenance of its activity
      throughout G1 is controlled via multiple phosphorylation events mediated by a
      complex signalling network acting on distinct sets of phosphorylation sites.

PMID- 9552352
TI  - MAP kinase-dependent pathways in cell cycle control.
AB  - Mitogen-activated protein kinases such as Erk1 and Erk2 serve as a paradigm for a
      growing family of proline-directed protein kinases that mediate entry,
      progression and exit from the cell cycle in diverse eukaryotic cells. These
      enzymes function within highly conserved modules of sequentially activating
      protein kinases that transduce signals from diverse extracellular stimuli. In
      vertebrates, at least three distinct kinases modules have been characterized.
      Mitogens induce the sequential activation of the kinases Raf1-->Mek1-->Erk2-->Rsk
      via the G-protein Ras. Stress factors stimulate c-Jun activation through a
      related kinase pathway involving Mekk-->Sek-->SAPK c-Jun, and hsp27
      phosphorylation via the MKK3-->Hog-->MAPKAPK-2 hsp27 route. Genetic and
      biochemical studies, for example from budding yeast, imply the existence of
      several related protein kinase modules that can operate in parallel or within
      integrated systems.

PMID- 9552354
TI  - Cell cycle control of DNA replication.
AB  - The cell cycle is driven by the sequential activation of a family of cyclin
      dependent kinases (cdk), which phosphorylate and activate proteins that execute
      events critical to cell cycle progression. In mammalian cells cdk2-cyclin A has a
      role in S phase. Many replication proteins are potential substrates for this cdk
      kinase, suggesting that initiation, elongation and checkpoint control of
      replication could all be regulated by cdk2. The association of PCNA, a
      replication protein, with cdk-cyclins during G-1 to S phase transition and with
      cdk-cyclin inhibitors, adds an interesting complexity to regulation of DNA
      replication.

PMID- 9552355
TI  - Cell cycle-regulated transcription in mammalian cells.
AB  - The periodic, phase-specific transcription of defined sets of genes is a hallmark
      of cell cycle progression in all organisms (1-3). In this article, we will
      summarise our current knowledge and views of the mechanisms governing the cross
      coupling of cell cycle control and transcriptional regulation in mammalian cells,
      with particular emphasis on the transcription factor E2F and the retinoblastoma
      protein pRb (1-3). Excluded from this review will be the genomic response to
      mitogenic stimulation, which is part of the mitogen-triggered signal transduction
      cascades rather than a reflection of cell cycle regulation (4).

PMID- 9552356
TI  - The CLN gene family: central regulators of cell cycle Start in budding yeast.
AB  - The Start transition in the budding yeast cell cycle is the point of most
      physiological regulation of cell cycle commitment. This transition is controlled
      by the CLN1,2,3 gene family. We review what is known about the regulation, inter
      regulation and function of these genes in controlling the Start transition.

PMID- 9552353
TI  - Mechanism of action of rapamycin: new insights into the regulation of G1-phase
      progression in eukaryotic cells.
AB  - The immunosuppressant drug, rapamycin (RAP), is a potent inhibitor of IL-2
      dependent T-cell proliferation. The antiproliferative effect of RAP is mediated
      through the formation of an active complex with its cytosolic receptor protein,
      FKBP12. The molecular target of the FKBP12.RAP complex is a putative lipid kinase
      termed the mammalian Target Of Rapamycin (mTOR). This review will discuss recent
      findings suggesting that mTOR is a novel regulator of G1- to S-phase progression
      in eukaryotic cells.

PMID- 9552357
TI  - Cyclin A: function and expression during cell proliferation.
AB  - Cyclin A is a key regulatory protein which, in mammalian cells, is involved in
      both S phase and the G2/M transition of the cell cycle through its association
      with distinct cdks. Several lines of evidence have also implicated cyclin A in
      carcinogenesis. Our review concentrates on the role of cyclin A in S phase, in
      the S/G2 transition and in human carcinogenesis; it will also discuss the
      transcriptional regulation of cyclin A gene.

PMID- 9552358
TI  - The role of cyclin E in the regulation of entry into S phase.
AB  - Cyclin E is a crucial regulator of entry into S phase in higher eukaryotes and
      acts in association with the protein kinase cdk2. Cyclin E expression is
      transcriptionally controlled in mammalian cells resulting in a maximum just
      before entry into S phase. Premature expression of cyclin E advances entry into S
      phase, while lack of cyclin E prevents entry into S phase. Cyclin E/cdk2 activity
      is regulated at multiple levels (by transcription, phosphorylation and inhibitor
      proteins) and appears to be involved in triggering initiation of DNA replication
      and in regulating genes important for proliferation and progression through S
      phase.

PMID- 9552359
TI  - p27KIP1, an inhibitor of cyclin-dependent kinases.
AB  - The identification of a family of proteins that stoichiometrically regulate the
      activation of the G1 cyclin-dependent kinases has added to our understanding of
      the process of commitment to the mitotic cycle. The properties of p27 as a CDK
      binding protein, the ability of environmental signals to regulate the expression
      of p27, and the observation that p27 may link the accumulation of G1 CDK
      complexes with activation of the CDK2 kinase, suggest it may have a critical role
      in establishing a threshold for G1 cyclin/CDK accumulation prior to activation of
      CDK2 kinase and entry into the mitotic cycle.

PMID- 9552360
TI  - Regulation of cell cycle progression following DNA damage.
AB  - DNA damage causes an arrest in cell cycle progression. Checkpoints, which monitor
      the state of the DNA, exist throughout the cycle and negatively regulate cell
      cycle transitions when damage is detected. The molecular basis of how these
      checkpoints are activated, and interact with the cell cycle machinery, is just
      beginning to be understood. Studies in yeast have identified a number of genes
      involved in a G2 DNA damage checkpoint, while in mammalian cells a G1 checkpoint
      has been extensively studied.

PMID- 9552361
TI  - The role of the Ran GTPase pathway in cell cycle control and interphase nuclear
      functions.
AB  - Ran is a small, highly abundant, nuclear GTPase. Mutants in Ran and in proteins
      that interact with it disrupt the normal checkpoint control of mitosis with
      respect to the completion of DNA synthesis. Ran and other components of this
      pathway are also required for numerous nuclear functions such as RNA export,
      protein import, RNA processing and DNA replication. It will be important to
      understand how these facets of Ran's activities are linked and how they promote
      correct control of the cell cycle. This review examines recent progress in
      discovering other components of the Ran GTPase pathway and considers how this
      pathway may be required for the control of the cell cycle.

PMID- 9552362
TI  - The Cdc28 inhibitor p40SIC1.
AB  - Sic1 inhibits the activity of Cdc28.Clb5 complexes in late G1, creating a delay
      between cell cycle commitment and S phase initiation. The ultimate purpose of
      this delay is unknown but loss of Sic1 activity negatively affects genomic
      stability and cellular viability. Sic1 levels are controlled by periodic changes
      in transcription rates and protein stability. The latter control is mediated
      through the Cdc34 ubiquitin transferase and, possibly, Cdc28.Cln activity.
      Possible roles of Sic1 in the G1/S and the M/G1 transitions are discussed.

PMID- 9552363
TI  - The NIMA kinase: a mitotic regulator in Aspergillus nidulans and vertebrate
      cells.
AB  - CDC2 has been shown to regulate entry into mitosis in eukaryotic cells. However,
      in Aspergillus nidulans, activation of CDC2 itself is not sufficient to trigger
      mitosis if another mitotic protein kinase, NIMA, is not activated. Superficially,
      NIMA and CDC2 have analogous functions and are regulated in a similar manner.
      NIMA activity is tightly regulated during the cell cycle. Overexpression of NIMA
      induces germinal vesicle breakdown in Xenopus oocytes and promotes premature
      entry into mitosis in all eukaryotic cells examined, whereas dominant-negative
      mutant NIMA causes a specific G2 arrest in Aspergillus nidulans and human cells,
      as is the case for CDC2. However, NIMA and CDC2 have quite distinct primary
      sequence substrate specificities. Furthermore, the regulatory mechanisms that
      govern the cell cycle-dependent abundance, activity and localization are largely
      intramolecular for NIMA but intermolecular for CDC2. More importantly, a NIMA
      like pathway is also required for the G2/M transition in vertebrate cells. Thus,
      NIMA may represent a new essential eukaryotic cell cycle regulator, although its
      homologues in other species are yet to be identified.

PMID- 9552364
TI  - The fission yeast Nim1/Cdr1 kinase: a link between nutritional state and cell
      cycle control.
AB  - Close connections appear to exist between extra-cellular signals that regulate
      cell proliferation and the protein kinases that control the cell cycle machinery.
      The fission yeast nim1 kinase is an inducer of cdc2 kinase activity acting
      through the inhibition of wee1 kinase. Nim1 function is required for a correct
      cellular response to nutritional starvation. In the absence of nim1, starved
      cells are unable to decrease their size at mitosis, to arrest their cycle in G1
      and to enter G0. Here, we review our current knowledge on the role and the
      regulation of nim1 in connecting cell cycle and nutritional pathways.

PMID- 9552365
TI  - Function and regulation of cdc25 protein phosphate through mitosis and meiosis.
AB  - Activation of the cyclin B-cdc2 kinase mitotic inducer involves dephosphorylation
      of two inhibitory residues, tyrosine 15 and threonine 14, cdc25 is the specific
      phosphatase that directly dephosphorylates and activates the cdc2 kinase, cdc25
      activity is regulated by phosphorylation. Both phosphatases 1 and 2A could act as
      cdc25-specific inhibitory phosphatases. Although the cyclin B-cdc2 complex plays
      a role in activating cdc25, it is highly probable that a distinct protein kinase
      is involved as a trigger in cdc25 activation. The implication of raf kinase as a
      cdc25-specific activating kinase in human cells and Xenopus oocytes is discussed.

PMID- 9552366
TI  - The regulation and functions of cdk7.
AB  - cdk7 started its life rather anonymously as a kinase called MO15, identified
      during a search for cDNA's which encode protein kinases related to cdc2. For
      several years its function remained obscure, but during the last 18 months MO15
      has revealed itself as the catalytic subunit of cdk activating kinase,
      associating with at least two other subunits including a new cyclin, cyclin H.
      MO15(cdk7) has therefore been established paradoxically as both a new member and
      a regulator of the cyclin dependent kinase family. New evidence now suggests that
      cdk7 is also involved in the processes of transcription initiation and DNA
      repair, associating with the general transcription factor TFIIH. The engima of
      cdk7 is likely to remain for a while yet, and perhaps even more surprises are in
      store.

PMID- 9552367
TI  - Implications for cAMP-dependent protein kinase in the maintenance of the
      interphase state.
AB  - The cAMP dependent protein kinase (A-kinase) is one of the first and best studied
      kinases in mammalian cells. There is extensive evidence that A-kinase activity
      acts antagonistically toward mitotic entry both in oocyte and somatic cells.
      Firstly, A-kinase seems to directly compromise the activation process of the cdc2
      cyclin B mitotic kinase. Secondly, as shown by specific in vivo inhibition of A
      kinase using microinjection of a stable form of its inhibitor peptide PKI, A
      kinase modulates several key interphase cellular processes including cytoskeletal
      dynamics, transcription, chromatin structure and nuclear localization. We discuss
      the potential mechanisms involved in the down regulation of A-kinase activity at
      the interphase/mitosis transition.

PMID- 9552368
TI  - G-protein-mediated signal transduction for meiosis reinitiation in starfish
      oocyte.
AB  - Starfish oocyte maturation is induced by 1-methyladenine. There were apparently
      two forms of 1-methyladenine receptor affected by GTP gamma S. Pertussis toxin
      ADP-ribosylated the 39-kDa alpha subunit of a G protein and inhibited maturation.
      Also, the G protein was ADP-ribosylated by cholera toxin only when 1
      methyladenine was added. The purified G protein had an heterotrimeric structure
      consisting of 39 kDa alpha, 37 kDa beta, and 8 kDa gamma subunits. The deduced
      amino acid sequence of the cDNA of starfish G alpha was 89% identical to
      mammalian Gi-1 alpha. The purified starfish beta gamma-subunits induced
      maturation when they were microinjected into oocytes.

PMID- 9552369
TI  - Phosphorylation of elongation factor-1 (EF-1) by cdc2 kinase.
AB  - Elongation factor-1 (EF-1) is a major substrate for cdc2 kinase in Xenopus
      oocytes. The guanine-nucleotide exchange factor EF-1 beta gamma delta, appears to
      have a highly complex macromolecular structure containing several GTP/GDP
      exchange proteins, valyl-tRNA synthetase, and a putative anchoring protein EF-1
      gamma. During meiotic cell division, the factor becomes phosphorylated by cdc2
      kinase, not only on EF-1 gamma, but also on two different phospho-acceptors on EF
      1 delta. Phosphorylation is concomitant with changes in protein synthesis in
      vivo. Xenopus oocytes, and potentially all cells, contain a multitude of
      heteromeric forms of the complex which postulates that EF-1 beta gamma delta is
      not a "house keeping" factor but a sophisticated regulatory element.

PMID- 9552370
TI  - The regulation of mitotic nuclear envelope breakdown: a role for multiple lamin
      kinases.
AB  - The chapter reviews the structure and function of the nuclear envelope and
      describes its dynamic structural changes during cell cycle. Particular emphasis
      is placed on the regulation of mitotic nuclear envelope breakdown (NEBD), the
      process by which the physical barrier between cytoplasm and nucleus is dissolved
      to allow for cell division. The literature suggesting the involvement of multiple
      protein kinases in NEBD is reviewed and evidence is presented that multiple
      mitotic lamin kinases, including p34cdc2/cyclin B kinase and protein kinase C,
      play key roles in mitotic nuclear lamina disassembly. Finally, a model for
      regulation of mitotic nuclear lamina disassembly by multi-site phosphorylation is
      described.

PMID- 9552371
TI  - The MAP kinase cascade: its role in Xenopus oocytes, eggs and embryos.
AB  - Mitogen-activated protein kinase (MAPK) was originally identified as a
      serine/threonine kinase that is activated by mitogens. Now MAPK and its
      activator, MAPK kinase (MAPKK), are thought to function in a wide variety of
      intracellular signalling pathways from yeast to vertebrate. We describe here a
      brief summary of the dissection of the MAPK cascade and its possible functions,
      especially in Xenopus oocytes and embryos.

PMID- 9552372
TI  - The oocyte metaphase arrest.
AB  - Usually, oocyte meiosis reinitiation appears as a two step process during which
      release from the prophase block is followed by a second arrest in metaphase I or
      II. In this review, we will examine the mechanisms required to maintain the
      metaphase arrest and stabilize MPF activity at this stage. Then, we will analyse
      the processes required to exit from the metaphase block. These may drive the
      cells forward to the metaphase-anaphase transition, as a result of fertilization,
      activation or protein synthesis inhibition. Instead, inhibiting protein
      phosphorylation drives the oocyte back to interphase. All these treatments result
      in derepression of DNA synthesis.

PMID- 9552373
TI  - Onset of chromosome segregation at the metaphase to anaphase transition of the
      cell cycle.
AB  - Chromosome segregation is one of the most important acts in the life of the cell.
      Unequal inheritance of chromosomes (aneuploidy) is a cause of a number of
      disorders, particularly in humans, even though eukaryotic cells can arrest or
      delay the transition from metaphase to anaphase if an event critical to the
      completion of metaphase is impaired. In this report, we review recent advances in
      our knowledge of how the complex process of chromosome segregation is coupled
      with cell cycle progression, and starts at onset of anaphase with sister
      chromatids separation of the replicated chromosomes.

PMID- 9552374
TI  - Mechanisms of chromosome segregation in metazoan cells.
AB  - Despite over 100 year of research, the mechanisms that cells use to ensure the
      proper segregation of chromosomes during mitosis are still surprisingly obscure.
      However, recent high resolution video light microscopic studies of dividing cells
      are telling us new and important information about chromosome behavior. Molecular
      genetics is enabling us to build a more complete list of the components involved
      in chromosome segregation. And in vitro assays for chromosome segregation are
      providing information about the signals that control the equipartitioning of
      sister chromatids during cell division.

PMID- 9552375
TI  - The PITSLRE protein kinase family.
AB  - A family of p34Cdc2 related protein kinases, the PITSLRE kinases, is generated by
      alternative splicing and promoter utilization from three duplicated and tandemly
      linked genes on human chromosome 1p36.3, which is frequently deleted during the
      late stages of tumorigenesis. PITSLRE mRNA, protein, and enzyme activity are
      induced during Fas receptor- and glucocorticoid-mediated apoptosis of human T
      cells. Several PITSLRE isoforms are specific targets of proteolysis during
      apoptosis, generating an enzymatically active 50 kDa isoform. Inhibition of this
      protease activity blocks PITSLRE processing and enzyme activation, as well as
      apoptosis. Thus, PITSLRE kinases may be integral downstream components of
      apoptotic signal transduction pathway(s). Furthermore, PITSLRE genes, and their
      products, are physically altered in human neuroblastoma tumors, suggesting that
      they may be tumor suppressors.

PMID- 9552376
TI  - Cell cycle regulation and functions of HMG-I(Y).
AB  - Members of the HMG-I(Y) family of "high mobility group" (HMG) proteins are
      distinguished from other nonhistone chromatin proteins by their ability to
      preferentially recognize the structure of the narrow minor groove of A.T
      sequences of B-form DNA. In vivo the HMG-I(Y) proteins are localized in the A.T
      rich G/Q bands and in the "scaffold-associated regions" (SARs) of metaphase
      chromosomes. These proteins also share with some of the other "HMG box" proteins
      the ability to recognize non-B-form structures, such as cruciforms (four-way
      junctions), as well as the possessing the capacity to introduce both bends and
      supercoils in substrate DNAs. These characteristics, along with their ability to
      specifically interact with a number of known transcription factors, enable the
      HMG-I(Y) proteins to function in vivo as structural transcription factors for a
      number mammalian genes. The HMG-I(Y) proteins are also in vivo substrates for the
      cell cycle regulated Cdc2 kinase which phosphorylates the DNA-binding domain(s)
      of the protein and, as a result, decreases their substrate binding affinity. This
      reversible in vivo pattern of Cdc2 kinase phosphorylations during the cell cycle
      is likely to play a major role in mediating the biological function(s) of the HMG
      I(Y) proteins.

PMID- 9552377
TI  - Chemical inhibitors of cyclin-dependent kinases.
AB  - The eukaryotic cell division cycle is regulated by a family of protein kinases,
      the cyclin-dependent kinases (cdk's), constituted of at least two subunits, a
      catalytic subunit (cdk1-7) associated with a regulatory subunit (cyclin A-H).
      Transient activation of cdk's is responsible for transition through the different
      phases of the cell cycle. Major abnormalities of cdk's expression and regulation
      have been described in human tumours. Enzymatic screening is starting to uncover
      chemical inhibitors of cdk's with anti-mitotic activities. This review summarizes
      our knowledge of these first inhibitors, their mechanism of action, their effects
      on the cell cycle, and discusses the potential of such type of inhibitors as anti
      tumour agents.

PMID- 9552378
TI  - A quest for cytoplasmic factors that control the cell cycle.
AB  - Between 1966 and 1986 the author and his former students carried out an
      investigation into the cytoplasmic factors that regulate nuclear behaviour during
      meiotic maturation of oocytes. This anecdotal chronicle traces the development of
      the problems and the direction in which their solutions were attempted in the
      course of this investigation. The author examines why he decided to study oocyte
      maturation, how he discovered progesterone as a maturation-inducing hormone and
      maturation promoting factor (MPF) and cytostatic factor (CSF) as meiosis
      controlling factors, how the idea of the cell cycle without the cell occurred to
      him, and how it was materialised by invention of a cell-free system.

PMID- 9552379
TI  - G1/S regulatory mechanisms from yeast to man.
AB  - Cyclin-dependent kinases play a key role in promoting and regulating the
      transition from G1 to S phase in all eukaryotic organisms. The kinase activities
      involved are distinguished from those participating in other cell cycle phase
      transitions in that they are driven by a class of specialised G1-specific
      cyclins. Although the G1 regulatory components have diverged structurally in the
      course of evolution, the regulatory mechanisms and principles remain highly
      conserved from yeast to vertebrates. An important issue that remains is that of
      identifying the principal targets phosphorylated by G1 cyclin-dependent kinases.

PMID- 9552380
TI  - Regulation of G1 progression in fission yeast by the rum1+ gene product.
AB  - Recently it has been found that B-type cyclins in fission yeast regulate the
      activation of the cdc2 kinase to promote the onset of both DNA replication and
      mitosis. cig2 is the major G1 cyclin while cdc13 is the principal mitotic cyclin.
      cdc13 also has an additional function in G2 phase, preventing more than one round
      of DNA replication per cell cycle. In opposition to these cyclins the rum1
      inhibitor, a protein present exclusively in G1, prevents premature activation of
      the cdc2/cig2 and the cdc2/cdc13 complexes until cells have reached the critical
      cell size required to pass Start and initiate a new cell cycle.

PMID- 9552381
TI  - Progression through G1 and S phases of adult rat hepatocytes.
AB  - Regenerating liver, hepatocyte primary cultures and differentiated hepatoma cell
      lines are widely used to study the proliferation/differentiation/apoptosis
      equilibrium in liver. In hepatocytes, priming factors (TNF alpha, IL6) target
      G0/G1 transition while growth factors (HGF, EGF, TGF alpha) control a mid-late G1
      restriction point. A characteristic pattern of cdk/cyclin expression is observed
      in hepatocytes, presumably related to their ability to proliferate a limited
      number of times and to undergo a reversible differentiation. Interestingly, cell
      cell interactions between hepatocytes and liver biliary cells in co-cultures,
      result in a cell cycle arrest in mid G1 of hepatocytes which are insensitive to
      mitogens. Apoptosis exists in hepatocytes but is still poorly documented.
      However, hepatoma cell lines stimulated by TGF beta undergo cell death in a p53
      independent pathway. In conclusion, the interplay of growth and apoptosis
      regulators and cell-cell interactions control the
      proliferation/differentiation/apoptosis balance which is a specific feature of
      hepatocytes.

PMID- 9552382
TI  - A temporal and biochemical link between growth factor-activated MAP kinases,
      cyclin D1 induction and cell cycle entry.
AB  - Cell cycle re-entry requires the growth factor-stimulation of at least two
      distinct classes of protein kinases: (i) the p42/p44 MAP kinases activated by the
      Ras > Raf > MKK cascade and (ii) the G1 cyclin-dependent protein kinases (CDKs).
      Specific inactivation of either class of kinase arrests fibroblasts in G1. Growth
      factors promote nuclear translocation and persistent activation of p42/p44 MAP
      kinases during the entire G0/G1 period. Here, we demonstrate that induction of
      cyclin D1, and therefore cdk4/6 activity associated with, is positively
      controlled by the p42/p44 MAP kinase cascade whereas the parallel
      cytokines/stress-activated p38MAP kinase cascade is antagonistic. Finally, using
      an antisense approach we demonstrate that p27Kip1 plays a key role in setting the
      growth factor-dependency of the G0 state.

PMID- 9552383
TI  - The plant cell cycle: conserved and unique features in mitotic control.
AB  - Somatic plant cells can use a hormone checkpoint in late G2 phase. Here cytokinin
      stimulates removal of phosphotyrosine from p34cdc2 kinase and concurrently
      capacity for activation of the kinase by Cdc25 phosphatase declines while
      activity of the kinase increases and cells enter mitosis. Processes unique to
      plant mitosis are driven by the mitotically active kinase since the enzyme taken
      from plant cells in metaphase, when injected, can disassemble the preprophase
      band microtubules that form in G2 phase at the site of the future cross wall.
      This action is specific, since microtubules are not depolymerised when in
      interphase cytoplasmic array, or spindle, or phragmoplast. Plant metaphase kinase
      acts as MPF by accelerating chromosome condensation and nuclear envelope
      breakdown.

PMID- 9552384
TI  - The functions of Myc in cell cycle progression and apoptosis.
AB  - c-myc has emerged as one of the central regulators of mammalian cell
      proliferation. The gene encodes a transcription factor of the HLH/leucine zipper
      family of proteins that activates transcription as part of a heteromeric complex
      with a protein termed Max. In mammalian fibroblasts, Myc acts as an upstream
      regulator of cyclin-dependent kinases and functionally antagonises the action of
      at least one cdk inhibitor, p27. Myc also induces cells to undergo apoptosis, and
      the relationship between Myc-induced cell cycle entry and apoptosis is discussed.

PMID- 9552385
TI  - DNA replication licensing factor.
AB  - DNA Replication Licensing Factor (RLF) is an essential activity required to
      restrict the duplication of genomic DNA to precisely once per cell cycle. Recent
      fractionation of RLF activity from Xenopus egg extracts has resulted in the
      identification of two essential components, RLF-B and RLF-M. RLF-M has been
      purified to homogeneity and has been shown to consist of a complex of proteins in
      the MCM/P1 family. RLF-B is still unidentified, but possible candidates for this
      activity have been identified in yeast. Elucidation of the RLF mechanism will
      provide important insights into the way that chromosome replication is
      controlled.

PMID- 9552386
TI  - Tyrosine kinases wee1 and mik1 as effectors of DNA replication checkpoint
      control.
AB  - Cell cycle studies have revealed mechanisms that prevent cell division if DNA
      fails to be completely replicated or sustains damage. Here we focus on the
      evidence from yeast genetics that the wee1 and mik1 tyrosine kinases cooperate in
      the inhibitory phosphorylation of cdc2p, and the possibility that these kinases
      function in pathways that ensure the integrity of the genome prior to cell
      division. We also review the progress in cloning and analysing wee1-like tyrosine
      kinases from higher eukaryotes, and the evidence for and against their
      functioning in ensuring DNA replication prior to mitosis. Finally, we discuss the
      genes involved in these feedback controls and suggest that wee1p and mik1p might
      be the ultimate effectors that prevent mitosis when a checkpoint is triggered.

PMID- 9552387
TI  - Regulation of Cdc2 activity by phosphorylation at T14/Y15.
AB  - The highly conserved Cdc2 serine/threonine kinase plays a central role in cell
      cycle progression. Although Cdc2 levels remain constant throughout the cell
      cycle, Cdc2 kinase activity peaks at the G2/M boundary, in order to drive entry
      into mitosis. In the model organism Schizosaccharomysces pombe, potentially
      active Cdc2/Cdc13 kinase complex accumulates throughout the S and G2 phases of
      the cell cycle. This complex, however, is maintained in an active state by
      Wee1/Mik1-mediated phosphorylation at Y15 (and, possibly, T14). At the G2/M
      boundary, the Cdc25 protein phosphatase is activated to dephosphorylate the
      Cdc2/Cdc13 complex, resulting in abrupt activation of Cdc2 kinase activity and
      entry into mitosis.

PMID- 9552388
TI  - The family of polo-like kinases.
AB  - Here we discuss members of a new family of serine/threonine protein kinases with
      a likely role in cell cycle control. These kinases are referred to as polo-like
      kinases, after the prototypic founding member of the family, the polo gene
      product of Drosophila melanogaster. The polo kinase was originally identified in
      mutants that display abnormal mitotic spindle organization. Subsequently,
      potential homologues of Drosophila polo have been identified in yeasts (Cdc5p in
      Saccharomyces cerevisiae; plo1+ in Schizosaccharmoyces pombe) and in mammals
      (polo-like kinase 1; Plk1). Genetic and biochemical studies suggest that polo,
      Cdc5p and plo1+ may be required for mitotic spindle organization and, possibly,
      for cytokinesis. Likewise, the patterns of expression, activity and subcellular
      localization of Plk1 strongly suggest that this mammalian kinase functions also
      during mitosis, possibly in spindle assembly and function. In addition to Plk1,
      however, more distantly related members of the polo-like kinase family have been
      identified in mammalian cells, and the available data are consistent with the
      idea that some of these may act earlier in the cell cycle, possibly during G1. If
      this hypothesis is correct, different members of the polo-like kinase family
      would act at several points during the cell cycle, reminiscent of the behaviour
      of Cdk/cyclin complexes.

PMID- 9552389
TI  - Ubiquitin-dependent proteolysis and cell cycle control in yeast.
AB  - Genetic and biochemical data indicate that ubiquitin-mediated proteolysis is
      involved in the regulated turnover of proteins required for controlling cell
      cycle progression. In general, mutations in some genes that encode proteins
      involved in the ubiquitin pathway cause cell cycle defects and affect the
      turnover of cell cycle regulatory proteins. Furthermore, some cell cycle
      regulatory proteins are short-lived, ubiquitinated, and degraded by the ubiquitin
      pathway. This review will examine how the ubiquitin pathway plays a role in
      regulating progression from the G1 to the S phase of the cell cycle, as well as
      the G2 to M phase transition.

PMID- 9552390
TI  - Suc1: cdc2 affinity reagent or essential cdk adaptor protein?
AB  - CKS proteins, for which the original member, p13suc1, was identified as a
      suppressor of cdc2 alleles in S. Pombe, have long served as a reagent for the
      purification of p34cdc2, whereas their biological function has remained elusive.
      Apparently conflicting data derived from different model systems may indicate a
      diversity of function for these proteins. Several new observations in yeast and
      Xenopus egg extracts together with new structural information tends to enhance
      the hypothesis that CKS proteins function to alter the activity of cdc2 at
      several important points in the cell cycle. Here we review previous observations
      and recent data that suggest CKS proteins serve as adaptor proteins that modify
      the functions of cdc2 throughout the cell cycle.

PMID- 9552391
TI  - Structural basis for chemical inhibition of CDK2.
AB  - The central role of cyclin-dependent kinases (CDKs) in cell cycle regulation
      makes them a promising target for discovering small inhibitory molecules that can
      modify the degree of cell proliferation. The three-dimensional structure of CDK2
      provides a structural foundation for understanding the mechanisms of activation
      and inhibition of CDK2 and for the discovery of inhibitors. In this article five
      structures of human CDK2 are summarised: apoprotein, ATP complex, olomoucine
      complex, isopentenyladenine complex, and des-chloro-flavopiridol complex.

PMID- 9552393
TI  - DNA damage checkpoints: implications for cancer therapy.
AB  - DNA damage evokes a complex array of cellular responses, including cycle arrest
      in late G1 and/or G2 phases, and delayed progression through S phase. Arrest at
      these points in the cell cycle is governed, in large part, by a series of control
      systems, commonly termed "checkpoints". Activation of these checkpoints tends to
      protect cells from DNA damage by providing cells additional time to complete DNA
      repair. We discuss the impact of these DNA damage checkpoints on the
      chemosensitivity of human cancer cells. We focus on some of the complexities of
      the p53-dependent G1 checkpoint and review some recently discovered
      vulnerabilities in p53 disrupted cells that might be pharmacologically exploited
      for cancer treatment.

PMID- 9552392
TI  - Apoptosis and the cell cycle.
AB  - Apoptosis is a genetically controlled response by which eukaryotic cells undergo
      programmed cell death. This phenomenon plays a major role in developmental
      pathways (1), provides a homeostatic balance of cell populations, and is
      deregulated in many diseases including cancer. Control of cell number is
      determined by an intricate balance of cell death and cell proliferation.
      Accumulation of cells through suppression of death can contribute to cancer and
      to persistent viral infections, while excessive death can result in impaired
      development and in degenerative diseases. Identification of genes that control
      cell death, and understanding of the impact of apoptosis in both development and
      disease has advanced our knowledge of apoptosis in the past few years. There
      appears to be a linkage between apoptosis and cell cycle control mechanisms.
      Elucidating the mechanisms that link cell cycle control with apoptosis will be of
      key importance in understanding tumour progression and designing new models of
      effective tumour therapy.

PMID- 9552395
TI  - Telomeres, telomerase, and the cell cycle.
AB  - Telomeres protect the ends of chromosomes from degradation and fusion. In most
      eukaryotes telomeres are replicated by a specialised polymerase, telomerase.
      Telomerase synthesises one strand of the telomere; while conventional DNA
      polymerases synthesise the complementary strand. Additional processing of
      telomeres occurs in ciliates and yeast during each cell cycle. Telomerase
      activity and RNA levels change as cells enter and exit the cell cycle. Gradual
      telomere shortening in the absence of telomerase does not immediately affect cell
      cycling; however, "critically" short telomeres are hypothesised to play a role in
      senescence and the triggering of DNA damage checkpoints.

PMID- 9552394
TI  - Cellular responses to antimetabolite anticancer agents: cytostasis versus
      cytotoxicity.
AB  - Thymineless death is an important cytotoxic response to several classes of
      antimetabolite agents used in the treatment of patients with carcinomas and
      hematopoeitic malignancies. Cell death induced by lack of dThd results in the
      formation of DNA nucleosomal ladders, and hence would be defined as a form of
      apoptosis. Although drug resistance to these agents has been extensively studied,
      relatively little attention has been focused on events downstream of dTTP
      depletion that determine the ultimate fate of the cancer cell. In this article we
      review some of the emerging data that suggests the role of p53 in determining
      whether the cellular response to dThd deprivation is cytostasis or cytotoxicity
      (apoptosis).

PMID- 9552396
TI  - The cyclin C/Cdk8 kinase.
AB  - Cyclin C was originally identified in a genetic screen for metazoan cDNAs that
      complement a triple knock-out of the CLN genes, involved in G1/S progression in
      S. cerevisiae. Unlike cyclin Ds and cyclin E, also identified in this screen,
      cyclin C has not been found to have a cell-cycle role in metazoa. Identified as
      the catalytic partner of cyclin C, Cdk8 is a novel protein-kinase of the Cdk
      family structurally related to the yeast Srb10 kinase. Cyclin C, Cdk8 and RNA
      polymerase II are found in a large multi-protein complex that shows structural as
      well as functional homologies with the yeast polymerase II holoenzyme. These
      observations and the sequence similarity to the kinase/cyclin pair Srb10/Srb11 in
      S. cerevisiae, suggest that cyclin C and Cdk8 control RNA polymerase II function.

PMID- 9552397
TI  - Cyclin-dependent kinase 5 (Cdk5) and neuron-specific Cdk5 activators.
AB  - While cyclin-dependent kinase 5 (Cdk5) is widely distributed in mammalian tissues
      and in cultured cell lines, Cdk5-associated kinase activity has been demonstrated
      only in mammalian brains. An active form of Cdk5, called neuronal cdc2-like
      kinase (Nclk) has been purified from mammalian brain and shown to be a
      heterodimer of Cdk5 and a 25 kDa protein, which is derived proteolytically from a
      35 kDa brain and neuron-specific protein. The protein is essential for the kinase
      activity of Cdk5 and is therefore designated neuronal Cdk5 activator,
      p25/35Nck5a. Nclk appears to have important neuronal functions. The changes in
      Cdk5 and Nck5a expression appear to correlate with the terminal differentiation
      of neurons of the mouse embryonic brain. Transfection of cultured cortical
      neurons with dominant negative cdk5 mutants or Nck5a antisense DNA may reduce
      neurite growth, suggesting that Nclk plays an active role in neuron
      differentiation. A number of cytoskeletal proteins including neurofilament
      proteins, the neuron-specific microtubule associated protein tau, and the actin
      binding protein caldesmon are in vitro substrates of Nclk. Although Nck5a has
      cyclin-like activity, it shows minimal amino acid sequence identity to members of
      cyclin family proteins. The mechanism of activation of Cdk5 by Nck5a differs from
      that of cyclin activation of Cdks in that full Cdk5 kinase activity can be
      achieved in the absence of phosphorylation of Cdk5. An isoform of Nck5a, a 39 kDa
      protein has been cloned and shown to share extensive amino acid identity and the
      mechanism of Cdk5 activation with Nck5a. These proteins may represent a subfamily
      of Cdk activators distinct from cyclins.

PMID- 9552398
TI  - Role of Ca++/calmodulin binding proteins in Aspergillus nidulans cell cycle
      regulation.
AB  - The goal of this review is to summarise the current knowledge concerning the
      targets of Ca++/calmodulin that are essential for cell cycle progression in lower
      eukaryotes. Emphasis is placed on Aspergillus nidulans since this is the only
      organism to date shown to posses essential Ca++ dependent calmodulin activated
      enzymes. Two such enzymes are the calmodulin activated protein phosphatase,
      calcineurin and the calmodulin dependent protein kinase. These proteins, each the
      product of a unique gene, are required for progression of quiescent spores into
      the proliferative cycle and also for execution of the nuclear division cycle in
      exponentially growing germlings.

PMID- 9552399
TI  - The roles of DNA topoisomerase II during the cell cycle.
AB  - DNA topoisomerase II (topo II) is essential for survival of all eukaryotic cells.
      Topo II is both an enzyme and a structural component of the nuclear matrix. It
      regulates the topological states of DNA by transient cleavage, strand passing and
      re-ligation of double-stranded DNA resulting in decatenation of intertwined DNA
      molecules and relaxation of supercoiled DNA. Topo II plays an important role in
      DNA replication and is required for condensation and segregation of chromosomes.
      The expression of topo II is cell cycle dependent with both protein levels and
      catalytic activity peaking at G2/M. Phosphorylation/dephosphorylation of topo II
      may be a part of regulatory checkpoints at the entry and progression of mitosis.

PMID- 9552400
TI  - Circadian rhythm of cell division.
AB  - The existence of circadian oscillations in the level of hormones, in numerous
      physiological parameters, in toxicity and in behavior is now fully recognized in
      all living organisms. In contrast, the synchronisation and regulation of cell
      proliferation by circadian rhythms in vivo is only starting to be appreciated.
      This article reviews the experimental evidence for circadian synchronisation of
      cell division in different mammalian tissues (mainly the gastro-intestinal tract
      and hemapoietic system), including tumoral tissues. The possible causes of this
      coupling of the cell cycle phases to the circadian rhythm are discussed. Testing
      of novel antitumour agents using murine models should take into consideration the
      temporal difference between murine and human circadian control of proliferation
      (the peak of DNA synthesis occurs during the activity period, i.e. during daytime
      in man, and at night-time in mice and rats). Experimental and clinical data
      clearly support the important implications of the circadian control of the cell
      cycle in the optimisation of cancer chemotherapy, both for reducing toxicity and
      increasing the antitumour effects.

PMID- 9552401
TI  - The mammalian Golgi apparatus during M-phase.
AB  - The Golgi apparatus in mammalian cells disassembles into several thousand
      vesicles as cells enter M-phase. Disassembly is dependent on the action of cdc2
      kinase and at least two pathways contribute to the fragmentation: One involves
      the budding of COP-coated vesicles from Golgi cisternae with concomitant
      inhibition of fusion with their target membranes, the other is a less well
      characterised COP-independent pathway. During telophase, the Golgi fragments
      reassemble and fuse into a fully functional Golgi stack, using at least two
      distinct fusion pathways. The morphological changes of the Golgi apparatus during
      M-phase offer an ideal system to study how cellular organelles are generated and
      how their structure is maintained during interphase.

PMID- 9552402
TI  - Viruses and the cell cycle.
AB  - Viruses depend on the host's machineries to replicate and express their genome.
      Actively replicating cells have large pools of deoxynucleotides and high levels
      of key enzyme activities that viruses exploit to their own needs. Some viruses
      have developed strategies for driving quiescent cells into the S phase of the
      cell cycle, e.g. adenovirus, others, such as parvovirus, wait until the host
      itself begins to replicate. Viruses may also force the host cell to stay in a
      favourable phase, e.g. Epstein-Barr virus, or, if necessary, they may inhibit
      apoptotic cell death, e.g. human cytomegalovirus. In this review, we focus on the
      different strategies that viruses use to create in infected cells an environment
      favourable to the accomplishment of the viral life cycle through acting on cell
      cycle regulators.

PMID- 9552403
TI  - HIV-1 Vpr: G2 cell cycle arrest, macrophages and nuclear transport.
AB  - HIV-1 possesses six open reading frames in addition to the gag, pol, and env
      shared by all retroviruses. One of these accessory genes, vpr, is required for
      maximal viral replication in macrophages. The molecular mechanism underlying this
      effect may be related to one of the unusual properties of the encoded protein:
      some believe Vpr promotes nuclear translocation of preintegration complexes in
      non-dividing cells; also, Vpr arrests the cell cycle in G2 by inhibiting an
      upstream activator of p34cdc2-cyclin B. Elucidation of Vpr-cell cycle
      interactions may provide insight into both HIV-1 and basic cell biology.

PMID- 9552404
TI  - Regulation of cell division in plants: an Arabidopsis perspective.
AB  - Considerable progress has been achieved in the identification and molecular
      characterisation of genes and/or cDNAs coding for cyclin-dependent kinases (CDK)
      as well as cyclins in diverse plant species including Arabidopsis thaliana. Their
      transcriptional control during the cell cycle progression and the response to
      developmental cues and environmental signals has been studied in much detail,
      although the transcription factors mediating this regulation have yet to be
      identified. Experimental evidence has validated the involvement of CDKs and
      cyclins in cell division control in Arabidopsis and has revealed differential
      activation of two Arabidopsis CDKs in the course of the cell cycle. Finally, the
      first active CDK/cyclin pairs are being characterised, providing the basis for
      elucidation of their specific functions in cell cycle control and for unravelling
      the mechanisms that control their activity.

PMID- 9552406
TI  - Coordinate regulation of cell cycle and apoptosis during myogenesis.
AB  - During myogenesis, precursor cells irreversibly withdraw from the cell cycle as
      they differentiate into mature myotubes. The state of myocyte differentiation
      also influences the propensity of these cells to undergo apoptosis. Proliferative
      precursor cells are far more susceptible to apoptotic cell death than are
      terminally differentiated myotubes. The upregulation of the cdk inhibitor p21 and
      the dephosphorylation of pRb are critical regulatory events that establish both
      the post-mitotic and apoptosis-resistant states. The coordinate regulation of
      cell proliferation and death provides the organism with a mechanism to control
      the deposition of muscle mass during embryonic development.

PMID- 9552405
TI  - Intestinal cell cycle regulation.
AB  - The intestinal epithelium is maintained by a balance between proliferation,
      differentiation and death that occurs as cells migrate up the crypt-villus axis.
      Cell cycle regulators such as cyclins, cyclin-dependent kinases (Cdks) and Cdk
      inhibitory proteins are expressed in a distinct pattern along the crypt-villus
      structure, suggesting their role in controlling intestinal cells. This is
      supported by observations that these cell cycle proteins are regulated by growth
      factors, nutrients and cell-cell contact in cultured intestinal epithelial cells.
      One of the key regulators of intestinal cell proliferation and differentiation is
      transforming growth factor-beta, which is expressed in the gut epithelium.

PMID- 9552407
TI  - Cell cycle regulation of organelle transport.
AB  - Microtubule- and actin-based motors play a wide range of vital roles in the
      organisation and function of cells during both interphase and mitosis, all of
      which are likely to be under strict control. Here, we describe how one of these
      roles--the movement of membranes--is regulated through the cell cycle. Organelle
      movement in many species is greatly reduced in mitosis as compared to interphase,
      and this change occurs concomitantly with an inhibition of most membrane traffic
      functions. Data from in vitro studies is shedding light on how microtubule motor
      regulation may be achieved.

PMID- 9552408
TI  - Protein kinase CK2 ("casein kinase-2") and its implication in cell division and
      proliferation.
AB  - Protein kinase CK2 (also termed casein kinase-2 or -II) is a ubiquitous Ser/Thr
      specific protein kinase required for viability and for cell cycle progression.
      CK2 is especially elevated in proliferating tissues, either normal or
      transformed, and the expression of its catalytic subunit in transgenic mice is
      causative of lymphomas. CK2 is highly pleiotropic: more than 160 proteins
      phosphorylated by it at sites specified by multiple acidic residues are known.
      Despite its heterotetrameric structure generally composed by two catalytic (alpha
      and/or alpha') and two non catalytic beta-subunits, the regulation of CK2 is
      still enigmatic. A number of functional features of the beta-subunit which could
      cooperate to the modulation of CK2 targeting/activity will be discussed.

PMID- 9552409
TI  - The regulation of cyclin-dependent kinase inhibitors (CKIs).
AB  - Inhibitors of cyclin-dependent kinases (CKIs) play key roles in coordinating cell
      proliferation and development. They also function to control critical cell cycle
      transitions and as effectors of checkpoint pathways. The activity of CKIs is
      tightly controlled through the cell cycle and in response to various signals.
      Regulation generally affects the levels or availability of the CKIs rather than
      changing their intrinsic activities. Mechanisms controlling CKI function include
      the regulation of transcription, translation and proteolysis. In addition some
      signals appear to induce sequestration of CKIs within the cells, thereby changing
      their ability to interact with specific targets.

PMID- 9552410
TI  - Contribution of the dual coding capacity of the p16INK4a/MTS1/CDKN2 locus to
      human malignancies.
AB  - During the three last years, the so-called p16 locus on human chromosome band
      9p21 has been increasingly implicated in different cancers by a variety of
      alterations abolishing both copies of the p16INK4a/MTS1/CDKN2 gene and the
      adjacent p15INK4b gene, two members of a family of specific inhibitors of the
      cyclin D 1-3-CDK4/6 complexes that control cell cycle progression of the G1 to S
      phase. While these properties are characteristic of tumor suppressor genes,
      abundant experimental data have clearly identified a link between the loss of
      function of p16INK4a and tumorigenic processes. The role of p15INK4b alterations
      in the onset of natural and experimental tumors is less obvious. New light may be
      shed on the role of the p16 locus in tumor development by the recent finding that
      an alternative transcript from the p16INK4a gene encodes p19ARF, a negative
      regulator of cell cycle progression which is unrelated to p16 and p15 and does
      not act by binding any CDK. Hence, this protein appears to be an element of a
      novel negative cell cycle control mechanism, whose impairing might be involved in
      tumorigenesis.

PMID- 9552411
TI  - p21: structure and functions associated with cyclin-CDK binding.
AB  - The cyclin dependent kinase inhibitor, p21, is a multifunctional protein involved
      in coordinating the cellular response to negative growth signals. Induced by
      cellular damage under the transcriptional control of the p53 tumour suppressor
      protein, p21 interfaces with a number of cellular proteins involved in growth
      control. Although p21 has a diverse range of activities, from assembly factor to
      transcriptional modulator, its ability to interact with and regulate the activity
      of the cyclin dependent protein kinases is paramount to many of these functions.

PMID- 9552412
TI  - The cdc18 protein initiates DNA replication in fission yeast.
AB  - Recent work has demonstrated that cdc18p plays a crucial role in regulating the
      onset of S phase in fission yeast. cdc18p is a major product of START specific
      transcription and associates with ORC and MCM proteins which are required for the
      initiation of DNA replication. High expression of cdc18p induces continuing DNA
      synthesis and is thought to drive the assembly of initiation complexes. In
      addition to its role in bringing about DNA replication, cdc18p participates in
      the cell cycle checkpoint control linking S phase to START and mitosis. We
      propose that cdc18p is central to the molecular mechanism co-ordinating S phase
      and M phase in concert with changes in activity of the master cell cycle
      regulator, the cdc2 protein kinase.

PMID- 9552413
TI  - Cell cycle regulation of S phase entry in Saccharomyces cerevisiae.
AB  - Eukaryotic DNA replication is restricted to a narrow window of the cell cycle
      called S phase, and occurs once and only once during each cell cycle. The
      combination of genetic and biochemical approaches in the budding yeast
      Saccharomyces cerevisiae has proven extremely helpful for studying the cell cycle
      regulation of S phase entry. This review will try to summarise the most recent
      discoveries which led to a new model to explain how entry into S phase is
      regulated in eukaryotic cells.

PMID- 9552414
TI  - The role of cyclin E in cell proliferation, development and cancer.
AB  - Normal cell proliferation is under strict regulation governed by checkpoints
      located at distinct points in the cell cycle. The deregulation of these
      checkpoint events and the molecules associated with them may transform a normal
      cell into a cancer cell. One of these checkpoints whose deregulation results in
      transformation occurs at the Restriction point, near the G1/S boundary. The
      periodic appearance of one of the recently identified regulatory cyclins, cyclin
      E, coincides precisely with the timing of the Restriction point. The deregulation
      in the expression and activity of cyclin E has been associated with a number of
      cancers and is thought to be involved in the process of oncogenesis. In this
      chapter, we summarise the current knowledge on the regulation and apparent
      function of cyclin E in normal proliferating cells and in developing tissue and
      alterations of these processes in cancer.

PMID- 9552415
TI  - Multiple roles of the proliferating cell nuclear antigen: DNA replication, repair
      and cell cycle control.
AB  - The proliferating cell nuclear antigen (PCNA), the auxiliary protein of DNA
      polymerase delta and epsilon, is involved in DNA replication and repair. This
      protein forms a homotrimeric structure which, encircling DNA, loads the
      polymerase on the DNA template. A role for PCNA in the cell cycle control is
      recognised on the basis of the interaction with cyclins, cyclin-dependent kinases
      (cdks) and the cdk-inhibitor p21 waf1/cip1/sdi1 protein. Association with the
      growth-arrest and DNA-damage inducible proteins gadd45 and MyD118, further
      demonstrates the role of PCNA as a component of the cell cycle control apparatus.

PMID- 9552416
TI  - Aberrations of the G1- and G1/S-regulating genes in human cancer.
AB  - Deregulated cell proliferation is the hallmark of cancer, and convergent data
      from the fields of cell-cycle research and molecular oncology have revealed the
      key role played by abnormalities of the cell-cycle control genes in multistep
      tumorigenesis. Along with the p53-mediated DNA damage checkpoint, the G1
      governing pathway of D-type cyclins, their partner cyclin-dependent kinases
      (Cdk), Cdk inhibitors, and the retinoblastoma protein constitute a functional
      unit and prominent oncogenic target. We have learned a great deal about the
      molecular basis of G1 phase progression and G1/S transition, their proto
      oncogenic defects, and potential clinical significance including diagnostic and
      prognostic applications and new approaches to gene therapy of cancer.

PMID- 9552417
TI  - Regulation of p34cdc2/cyclinB H1 and NIMA kinases during the G2/M transition and
      checkpoint responses in Aspergillus nidulans.
AB  - In A. nidulans, activation of both p34cdc2/cyclinB H1 and NIMA kinases is
      required to initiate mitosis. These two kinases are regulated at several levels
      during interphase and are activated independently as protein kinases during G2.
      They are also targeted for negative regulation, to prevent mitosis by mitotic
      entry checkpoint controls, when DNA is not replicated or is damaged. Then, to
      initiate mitosis, they promote each other's mitotic functions to coordinately
      promote mitosis upon completion of interphase events. In addition, inactivation
      of both kinases by mitotic specific proteolysis is also required for progression
      through mitosis into G1.

PMID- 9552418
TI  - Myt1: a Wee1-type kinase that phosphorylates Cdc2 on residue Thr14.
AB  - Most somatic cell division cycles contain a gap period (G2 phase) between the
      completion of DNA synthesis and the initiation of mitosis. This delay of mitotic
      entry is controlled, at least in part, by the repression of Cdc2 kinase activity
      by the phosphorylation of two conserved residues (Thr14 and Tyr15) within the ATP
      binding pocket of the Cdc2 catalytic subunit. The kinases responsible for these
      two phosphorylation events include the Myt1 and Wee1 kinases, which phosphorylate
      Cdc2 on Thr14 and Tyr15, respectively. In this discussion, we summarise our
      current knowledge of the Myt1 kinase and its regulation of Cdc2 kinase activity
      during the G2-to -M phase transition.

PMID- 9552419
TI  - In vivo regulation of the entry into M-phase: initial activation and nuclear
      translocation of cyclin B/Cdc2.
AB  - The cyclin B/Cdc2 complex, Cdc2 kinase governs M-phase. Although the intracomplex
      modification for its activation in vitro has been described extensively, its
      regulation in vivo is not so well explained so far. In this article, we will
      focus on the intracellular regulation of the cyclin B/Cdc2 activity, in
      particular, how it is initially activated in vivo, how its nuclear translocation
      is executed specifically at the onset of M-phase, and how the activation and the
      nuclear translocation are coordinated in the cell. These concerted regulations
      may determine the appropriate timing for the initiation of M-phase.

PMID- 9552420
TI  - Mos and the cell cycle.
AB  - The mos proto-oncogene-encoded serine/threonine protein kinase plays a key cell
      cycle-regulatory role during meiosis. The Mos protein is required for the
      activation and stabilisation of M phase-promoting factor MPF. As a component of a
      large multiprotein complex known as the cytostatic factor (CSF), Mos is involved
      in causing metaphase II arrest of eggs in vertebrates. Upon expression in somatic
      cells, Mos causes cell cycle perturbations resulting in cytotoxicity and
      neoplastic transformation. All the known biological activities of Mos are
      mediated through activation of the mitogen activated protein (MAP) kinase
      pathway. Here we discuss the interrelationship between Mos and other cell cycle
      regulators.

PMID- 9552421
TI  - Calcium and mitosis.
AB  - Calcium signals often accompany mitosis. The most obvious example of calcium as a
      mitotic signal is at fertilization in vertebrate eggs, where the calcium
      transient induces anaphase onset. New imaging methods have demonstrated smaller
      calcium signals that control mitosis entry and mitosis exit in sea urchin
      embryos. Other experiments in mouse and frog embryos indicate that similar
      signals with similar function may play a part in these embryos, too. The links
      between these calcium control signals and mitotic kinase activation are
      adumbrated. It appears that calcium oscillations are a property of the mitotic
      state. A case is made that calcium may be a universal mitotic signal, with the
      possible exception of early meiotic events in oocytes.

PMID- 9552422
TI  - Role of chromosomes in assembly of meiotic and mitotic spindles.
AB  - The assembly of a mitotic spindle requires the interaction of microtubules with
      chromosomes. As a cell enters mitosis, long microtubules are converted to short
      ones, as microtubules become unstable. Dynamic microtubules are then stabilised
      by chromosomes, forming a bipolar spindle. In this review, we discuss the
      different roles of kinetochores and chromosome arms during spindle assembly.
      Kinetochores, required for proper chromosomes segregation, capture microtubules
      and maintain attachment. Chromosome arms greatly enhance microtubule stability,
      and alone can be sufficient for spindle assembly.

PMID- 9552423
TI  - Organisation and functional regulation of the centrosome in animal cells.
AB  - Molecular characterisation of centrosomal components is slowly progressing.
      Recent results indicate that the major aspects of centrosome-mediated microtubule
      nucleation may soon be understood at the molecular level. In contrast, centrosome
      reproduction, which is an important aspect of animal cell division, remains terra
      incognita. The most challenging issue for the future is to understand the
      molecular mechanisms which control centrosome biogenesis. There is a urgent need
      to identify with certainty proteins implicated in this process. Comparison
      between organisms with structurally different centrosomes might be critical for a
      better understanding of centrosome duplication if a general mechanism has been
      conserved throughout evolution.

PMID- 9552424
TI  - Mitosis and checkpoints that control progression through mitosis in vertebrate
      somatic cells.
AB  - During mitosis in vertebrates the sister kinetochores on each replicated
      chromosome interact with two separating arrays of astral microtubules to form a
      bipolar spindle that produces and/or directs the forces for chromosome motion. In
      order to ensure faithful chromosome segregation cells have evolved mechanisms
      that delay progress into and out of mitosis until certain events are completed.
      At least two of these mitotic "checkpoint controls" can be identified in
      vertebrates. The first prevents nuclear envelope breakdown, and thus spindle
      formation, when the integrity of some nuclear component(s) is compromised. The
      second prevents chromosome disjunction and exit from mitosis until all of the
      kinetochores are attached to the spindle.

PMID- 9552425
TI  - Will the Pharm.D. Make the pharmaceutics Ph.D. an endangered species?

PMID- 9552426
TI  - An in vitro method to investigate food effects on drug release from film-coated
      beads.
AB  - The influence of simulated high-fat meals on drug release from beads coated with
      modified-release ethylcellulose coating formulations was investigated as a
      function of plasticizer type and concentration, and coating level. Ethylcellulose
      coated beads were soaked in peanut oil prior to testing to simulate the influence
      of concomitant administration of the dosage form with ingestion of fatty meals.
      The USP apparatus 3 dissolution procedure was employed to study the drug release
      properties of the beads. It was found that the ethylcellulose-coated beads
      plasticized with either triethyl citrate (TEC) or dibutyl sebacate (DBS) had
      faster drug release rates after the peanut oil treatment. Scanning electron
      microscopy (SEM) revealed that the peanut oil soak caused the polymeric films to
      detach from the surface of the bead, producing a series of uneven ridges and
      cracks in the coating. Modulated differential scanning calorimetry (DSC)
      demonstrated that the glass transition temperature was increased for DBS
      plasticized films soaked in peanut oil, and that it was not influenced for TEC
      plasticized films. Similar results were found for the puncture strength, percent
      elongation, and modulus of elasticity for the DBS- and TEC-plasticized films
      soaked in peanut oil. The results verified that the DBS was solubilized and
      extracted from the plasticized film during the peanut oil soak, and that the film
      plasticized with the TEC was not significantly affected by the peanut oil soak.
      Drug release was influenced by the plasticizer type and concentration, and
      coating level applied to the beads.

PMID- 9552427
TI  - Evaluation of in vitro release rate and in vivo absorption characteristics of
      four metoprolol tartrate immediate-release tablet formulations.
AB  - The purpose of this investigation was to examine the impact of formulation and
      process changes on dissolution and bioavailability/bioequivalency of metoprolol
      tartrate tablets manufactured using a high-shear granulation process. A half
      factorial (2(4-1), Res IV) design was undertaken to study the selected
      formulation and processing variables during scale-up. Levels and ranges for
      excipients and processing changes studied represented level 2 or greater changes
      as indicated by the SUPAC-IR Guidance. Blend and tableting properties were
      evaluated. Changes in sodium starch glycolate and magnesium stearate levels, and
      the order of addition microcrystalline cellulose (intra- vs. extragranular) were
      significant only in affecting percent drug released (Q) in 5, 10, and 15 min.
      Statistical analysis of data showed no significant curvature. No interaction
      effects were found to be statistically significant. To examine the impact of
      formulation and processing variables on in vivo absorption, three batches were
      selected for a bioavailability study based on their dissolution profiles.
      Subjects received four metoprolol treatments (Lopressor, slow-, medium-, and fast
      dissolving formulations) separated by 1 week according to a randomized crossover
      design. After an overnight fast, subjects were administered one tablet (100 mg),
      blood samples were collected over 24 hr and plasma samples were analyzed. The
      formulations were found to be bioequivalent with respect to the log Cmax and log
      AUC0-infinity. The results of this study suggest that: (i)
      bioavailability/bioequivalency studies may not be necessary for metoprolol
      tartrate and perhaps other class 1 drugs after level 2 type changes and (ii) in
      vitro dissolution tests may be used to show bioequivalence of metoprolol
      formulations with processing or formulation changes within the specified level 2
      ranges for the equipment examined.

PMID- 9552428
TI  - Optimization and characterization of a pH-independent extended-release
      hydrophilic matrix tablet.
AB  - A simple systematic optimization approach was applied to tailor the drug release
      profile from a hydrophilic matrix extended-release tablet. When the ratio of
      anionic and nonionic polymers was optimized, pH-independent in vitro release of
      the model drug verapamil hydrochloride was obtained. The mechanisms of drug
      release at the pH extremes were evaluated by graphical analysis of the
      dissolution data and direct examination of the tablets during dissolution.
      Graphical evaluation did not completely clarify the release control mechanisms
      involved. Direct examination of tablets during dissolution, with estimation of
      amounts of drug and excipients dissolved at different times, gave further insight
      into relative contribution of mechanisms at different pH values. The change from
      predominantly diffusional to predominantly erosional mechanisms as pH is
      increased provides for the pH-independent release observed. This understanding
      should help model the application of this approach to other drugs.

PMID- 9552429
TI  - Reduced transdermal absorption of N,N-diethyl-m-toluamide from a new topical
      insect repellent formulation.
AB  - Extensive absorption of the topical insect repellent N, N-diethyl-m-toluamide
      (DEET) causes systemic and local toxicities. This report describes the
      preparation and characterization of a new insect repellent formulation (FA), a
      PEG-polyacrylic acid polymer system, for its DEET release, in vitro skin
      permeation, and in vivo transdermal absorption properties; and for its relative
      repellency against Aedes aegypti mosquitoes. DEET release and skin permeation
      were studied in Franz diffusion cells. DEET transdermal absorption and relative
      repellency of FA were assessed in beagle dogs. A commercial DEET lotion (FB) and
      technical DEET (FC) were used as references. FA exhibited 19.5% and 61.7%
      decrease in DEET steady-state skin flux compared with FB and FC, respectively. At
      15 mg DEET/kg, the absolute DEET transdermal bioavailability and Cmax were 13.4%
      and 154.3 ng/ml, respectively, for FA; and were 17.5% and 196.5 ng/ml,
      respectively, for FB. DEET half-lives (t1/2) for FA (2.52 hr) and FB (2.73 hr)
      were similar, while MRT for FA (4.99 hr) was significantly greater (p < 0.05)
      than that for FB (4.38 hr). FA showed lower mosquito biting rates at 1, 2, 3, 4,
      5, and 6 hr postdose at 0.5 mg DEET/cm2. FA exhibited reduced in vitro skin
      permeation and in vivo transdermal absorption of DEET as well as superior
      repellency compared with FB. The PEG-polyacrylic acid polymer system is of value
      in the formulation of DEET lotions.

PMID- 9552430
TI  - Drug solubility effects on predicting optimum conditions for extrusion and
      spheronization of pellets.
AB  - This paper explores the utility of aqueous solubility of structurally similar
      drugs in predicting optimum conditions for extrusion and spheronization of
      pellets using response surface methodology. Pharmacologically active xanthine
      derivatives exhibiting widely varying aqueous solubility were used to determine
      optimum conditions for pelletization. The amount of water added to the
      formulation, wet mixing time, and spheronizing time were explored in a series of
      central composite experimental designs to exhaustively explore and mathematically
      model the response surfaces for each drug. Using a marketed microcrystalline
      cellulose excipient, optimum extrusion and spheronization conditions for less
      soluble drugs required more water, a longer wet mixing time, and prolonged
      spheronizing times. Results were similar when a new microcrystalline cellulose
      was substituted, except that more water was required. When comparing results for
      different drugs, a strong linear relationship was observed between the aqueous
      solubility of the drug and the water content required for optimum pellet
      production. The water content range over which quality pellets could be produced
      was much broader for poorly soluble drugs. Aqueous solubility of the active
      component appears to be a good predictor for the water requirements for optimum
      extrusion and spheronization of pellets for pharmaceutical applications.

PMID- 9552431
TI  - Biodegradable cisplatin microspheres for direct brain injection: preparation and
      characterization.
AB  - The objectives of the present study were to prepare cisplatin loaded-PLGA
      microspheres that are suitable for direct brain injection and to characterize
      them in terms of their physicochemical properties, in vitro drug release, and
      self-removal mechanism. The microspheres were prepared by emulsification/solvent
      evaporation method using PLGA (50:50) as the biodegradable matrix forming
      polymer. The physicochemical characterization encompassed the following: surface
      morphology, particle size, entrapment efficiency, surface area, and density. The
      in vitro release and in vitro degradation studies were performed in phosphate
      buffer and in 10% rat brain preparation. SEM micrographs revealed that the
      microspheres have a rough porous surface and a smooth interior. Particle size
      typically ranged from 180 to 250 microns with an average of 230 T microns.
      Entrapment efficiency was approximately 70% and was found to be dependent on the
      particle size. Surface area and density ranged from 0.038 to 0.025 m2/g and from
      1.44 to 1.39 g/cm3, respectively. Both were also dependent on particle size. In
      the in vitro release study in phosphate buffer, approximately 80% of cisplatin
      was released over 30 days, after which the release rate plateaued. The release
      profile in 10% rat brain preparation was comparable in shape to that obtained in
      phosphate buffer. However, the release rate was lower and the total amount
      released by the end of the study was only 55% of the total cisplatin content. The
      degradation of PLGA microspheres in phosphate buffer and in rat brain homogenate
      correlated well with the respective release profiles. Based on the evidence of
      self-removal and the sustained release of cisplatin for over a month, cisplatin
      loaded PLGA microspheres may be useful for local delivery to brain tumors.

PMID- 9552432
TI  - Effect of particle morphology on emitted dose of fatty acid-treated disodium
      cromoglycate powder aerosols.
AB  - These studies assess the quantity and morphology of the emitted aerosolized dose
      of irregularly shaped disodium cromoglycate particles in the fine particle
      fraction using in vitro methods. Disodium cromoglycate was treated with a
      homologous series of saturated fatty acids, between C8 and C18, in a range of
      concentrations. The products of these treatments were powders with a variety of
      particle size, shape, and aggregation characteristics. Samples of these powders
      were loaded in gelatin capsules, generated as aerosols from a Rotahaler and
      collected in a two-stage liquid impinger or eight-stage inertial impactor.
      Particles were examined directly by scanning electron microscopy and subsequently
      the images were analyzed to define morphology. The aerodynamic fine-particle
      fraction determined by the two-stage impinger increased approximately twofold
      with lauric acid treatment (0.0317 g/g, 6.7%) and threefold with stearic acid
      treatment (0.58 g/g; 9.7%) compared with disodium cromoglycate alone (0 g/g,
      3.56%). The lauric acid formulation appeared to alter deposition primarily by
      changing particle morphology. Stearic acid altered particle shape to some extent
      and the increase in the fine-particle fraction appeared to be attributable to
      improved particle dispersion properties. The uncontrolled presence of irregular
      shaped particles can introduce dosing errors due to effects on dispersion and
      aerodynamic behavior. Conversely, controlled particle morphology and size may be
      employed to optimize the dose delivered to the lungs particularly if particle
      particle and particle-surface interactions can be minimized.

PMID- 9552433
TI  - Effect of sorbitol on the phosphate adsorptive capacity of ferrihydrite
      suspensions.
AB  - The purpose of this study was to stabilize the phosphate adsorptive capacity of
      aqueous suspensions of ferrihydrite, a potential phosphate binder. Ferrihydrite
      was precipitated by the addition of 1 N NaOH to 1 M FeCl3 until pH 8.0 was
      reached. The ferrihydrite suspension was divided into three portions and an
      amount of sorbitol was added to produce sorbitol concentrations of 0, 1, or 5%
      w/v, respectively. The phosphate adsorptive capacity and X-ray diffraction
      pattern were periodically determined during aging at room temperature. The
      phosphate adsorptive capacity of the ferrihydrite suspension containing 0%
      sorbitol decreased steadily from 0.012 mgP/mg to 0.007 mgP/mg during the 1-year
      aging period. In contrast, suspensions containing 1 or 5% sorbitol exhibited
      constant phosphate adsorptive capacities during this period. X-ray diffraction
      patterns revealed that ferrihydrite transformed to hematite and goethite during
      aging of the control suspension. The presence of 1 or 5% sorbitol prevented the
      transformation of ferrihydrite to more crystalline iron oxides. This study
      suggests that the phosphate adsorptive capacity of ferrihydrite suspensions can
      be stabilized by the incorporation of small amounts of sorbitol into the
      formulation.

PMID- 9552434
TI  - Calculation of intensified sampling plans in blending validation.

PMID- 9552435
TI  - Industrial scientists and engineers: an underutilized academic resource.

PMID- 9552436
TI  - Basic concepts of artificial neural networks (ANN) modeling in the application to
      pharmaceutical development.
AB  - Artificial neural networks (ANN) methodology is a new modeling method that has
      not been broadly applied to pharmaceutical sciences up to now. The aim of this
      paper is to give a detailed description of the associating networks as well as a
      description of less well-known networks (i.e., feature-extracting and nonadaptive
      networks) and their scope of application in pharmaceutical sciences. The
      descriptions include the historical origin and the basic concepts behind the
      computing. ANN are based on the attempt to model the neural networks of the
      brain. Learning algorithms for associating ANN use mathematical procedures
      usually derived from the gradient descent method whereas feature-extracting ANN
      map multidimensional input data sets onto two-dimensional spaces. Nonadaptive ANN
      map data sets and are able to reconstruct their patterns when presented with
      corrupted or noisy samples. Associating networks can typically be applied in the
      pharmaceutical field as an alternative to traditional response surface
      methodology, feature-extracting networks as alternative to principal component
      analysis, and nonadaptive networks for image recognition. Based on these
      abilities, the potential application fields of the ANN methodology in the
      pharmaceutical sciences is broad, ranging from clinical pharmacy through
      biopharmacy, drug and dosage form design, to interpretation of analytical data.
      The few applications presented in the pharmaceutical technology area seem
      promising and should be investigated in more detail.

PMID- 9552437
TI  - Application of artificial neural networks (ANN) in the development of solid
      dosage forms.
AB  - The application of ANN in pharmaceutical development has been assessed using
      theoretical as well as typical pharmaceutical technology examples. The aim was to
      quantitatively describe the achieved data fitting and predicting abilities of the
      models developed with a view to using ANN in the development of solid dosage
      forms. The comparison between the ANN and a traditional statistical (i.e.,
      response surface methodology, RSM) modeling technique was carried out using the
      squared correlation coefficient R2. Using a highly nonlinear arbitrary function
      the ANN models showed better fitting (R2 = 0.931 vs. R2 = 0.424) as well as
      predicting (R2 = 0.810 vs. R2 = 0.547) abilities. Experimental data from a tablet
      compression study were fitted using two types of ANN models (i.e., multilayer
      perceptrons and a hybrid network composed of a self-organising feature map joined
      to a multilayer perception). The achieved data fitting was comparable for the
      three methods (MLP R2 = 0.911, SOFM-MLP R2 = 0.850, and RSM R2 = 0.897). ANN
      methodology represents a promising modeling technique when applied to
      pharmaceutical technology data sets.

PMID- 9552438
TI  - Determination of (pseudo)plastic flow properties of pharmaceutical semisolids
      using rheological AUC parameters.
AB  - The purpose of this study was to develop a simple and unique method of data
      reduction for pharmaceutical semisolids. Application and accuracy of different
      regression models for rate-controlled rotating cylinder and T-shaped spindle data
      was compared in a conventional analysis of variance. Methods employed to
      determine area under the flow curve (AUC) parameters included integration of
      fitting function, planimetration, and calculation of trapezoids. Complex
      rheological behavior such as structure breakdown at low rates of shear (D) and
      deflocculation of particle aggregates at high values for D is not sufficiently
      described by conventional fitting functions. Iterating the nonlinear power law
      function tau = tau 0 + k2. Dn0, however, gives the best fit of data for
      pharmaceutical samples, estimating a yield value, tau 0.1 calculated for D = 0.1
      s-1 following double logarithmic transformation. Alternatively, rheological AUC
      parameters are determined for D: 0 < or = D < or = 98 s-1. Validating models,
      maximum deviation for different methods of determination is smaller than Srel of
      5 consecutive planimetration experiments. In case of sufficient fit of
      experimental data, integration of a nonlinear power law function is acceptable.
      Convenient fitting parameters tau and n0 can be substituted by area parameters
      such as AT, Arel, or R for all liquids, and hydrophilic and lipophilic gels, as
      well as o/w and w/o emulsions being investigated. The new AUC method offers
      robust data reduction and universal pharmaceutical application for different
      Newtonian and (pseudo)plastic materials. The approach is, however, limited to
      instrumental conditions and the range of D.

PMID- 9552439
TI  - Preparation and characterization of agarose hydrogel nanoparticles for protein
      and peptide drug delivery.
AB  - The purpose of this work was to develop and characterize a protein and peptide
      injectable drug delivery system in agarose hydrogel nanoparticles. The
      nanoparticles were prepared by using a new emulsion-converted-to-suspension in
      situ method. This is an emulsifier-free method that has advantages for protein
      and peptide drug encapsulations. Ovalbumin, used as a model protein drug, was
      successfully encapsulated into nearly spherical agarose hydrogel nanoparticles
      under mild conditions. The nanoparticles possessed a log-normal size distribution
      with an average size of 504 nm. They imbibed a large amount of water (66.85% to
      84.33%) and the water content was a function of temperature; the water content
      increased with increase in temperature. Release studies of the ovalbumin from the
      agarose hydrogel nanoparticles revealed a diffusion-controlled release mechanism
      with a temperature dependence; the ovalbumin release rate was higher at 37
      degrees C than that at room temperature. The great biocompatibility of agarose
      hydrogel, plus the mild conditions for drug encapsulation, make the agarose
      hydrogel nanoparticles a potential system for protein and peptide drug delivery.

PMID- 9552440
TI  - Use of poloxamer polymers to stabilize recombinant human growth hormone against
      various processing stresses.
AB  - Several processing and shipping stresses were investigated for their effect on
      the physical stability of recombinant human growth hormone (rhGH). These included
      exposure to air/water interfaces, adsorption to hydrophobic surfaces, freeze-thaw
      cycles, and temperature. The interfacially and thermally denatured hormone was
      evaluated for the presence of insoluble and soluble aggregates by
      spectrophotometry and by size-exclusion chromatography, respectively. Noncovalent
      aggregates were generated by either vortexing or multiple passages through a
      hypodermic needle, processes which exposed the protein to air/water interfaces.
      Thermal stress also resulted in the generation of aggregates. This aggregation
      was reduced or eliminated by the use of poloxamer polymers. Under the conditions
      employed, filtration through some commercially available filters, exposure to
      hydrophobic beads, or multiple freeze-thaw cycles did not produce any aggregates
      within the limitations of the analytical procedures used. Based on this study,
      Poloxamer 407 was found to be the most effective stabilizer for rhGH for
      protection against interfacial and thermal stress.

PMID- 9552441
TI  - Solid tumor chemotherapy and in vivo distribution of fluorouracil following
      administration in poly(L-lactic acid) microspheres.
AB  - The physicochemical properties and in vivo distribution of poly(L-lactide) (L
      PLA) microspheres containing 5-fluorouracil (5-FU) prepared by a solvent
      evaporation method were evaluated for potential use in the treatment of liver
      cancers. Two different molecular weight polymers of L-PLA [L-PLA1 (152,500 Da)
      and L-PLA2 (52,000 Da)] were used to prepare 5-FU-loaded microspheres. The mean
      particle size of the microspheres was 3-6 microns, and there was a direct
      relationship between the mean particle size and the molecular weight of the
      polymers. The drug release behavior from microspheres exhibited a diffusion
      mechanism in different dissolution media, with the molecular weight of the
      polymer being a major factor in controlling the drug release and degradation
      rates. Following intravenous injection of 99mTc-labeled L-PLA microspheres, with
      or without 5-FU, or free 5-FU into mice, L-PLA2 microspheres localized mainly in
      the liver. The disappearance rate of radioactivity from the tissue was very slow
      in comparison to that of free 5-FU. The results were confirmed by histological
      examination of liver tissue following administration of fluorescein particles. In
      addition, growth of a human liver tumor as first transplant generation under the
      renal capsule of immunocompetent rats and antitumor activity of L-PLA2
      microspheres were investigated. Histological examination by optical microscopy
      showed that there was no neoplastic tissue of the kidney or in other tissues
      examined after treatment.

PMID- 9552442
TI  - Sustained release of acetaminophen from heterogeneous matrix tablets: influence
      of polymer ratio, polymer loading, and co-active on drug release.
AB  - The aim of this research was to investigate the effect of pseudoephedrine (PE),
      polymer ratio, and polymer loading on the release of acetaminophen (APAP) from
      hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices.
      Granules formulated with APAP or both APAP and PE, and various blends of HPMC and
      PVP were compressed into tablets at varying compression forces ranging from 2000
      to 6000 Ib. In vitro drug release from the matrix tablets was determined and the
      results correlated with those of tablet water uptake and erosion studies. Drug
      release from the formulations containing both APAP and PE was slower than those
      containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated
      with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total
      polymer loading (> or = 9.6%). Formulations containing both APAP and PE showed
      slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the
      percentage of APAP released occurred after 18 hours. This was due to the
      hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to
      the Korsmeyer and Peppas model, and the values of the release exponents ranged
      from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion
      studies indicated that the amount of APAP released was linearly related to the
      percentage of tablet weight loss. The kinetics of tablet water uptake was
      consistent with a diffusion and stress relaxation controlled mechanism. Overall,
      the results of this study indicated that PE, as a co-active in the formulation,
      modified the matrix, and hence retarded APAP release.

PMID- 9552443
TI  - In vivo evaluation for rhGM-CSF wound-healing efficacy in topical vehicles.
AB  - The wound-healing efficacy of recombinant human granulocyte-macrophage colony
      stimulating factor (rhGM-CSF) was studied in a mouse model. Full-thickness wounds
      were treated with liquid crystalline, emulsion, and niosome vehicles alone and
      with rhGM-CSF. The control group was non-medicated. Observation of the vehicle
      groups with and without the rhGM-CSF displayed better healing profiles than the
      control group. The vehicles were also evaluated among themselves and it was noted
      that emulsion base and niosome base groups gave significantly better healing
      profiles and histological results than the liquid crystalline base group. Among
      the rhGM-CSF containing groups, emulsion formulation displayed a stronger wound
      healing effectiveness compared to the other formulations. In vitro release
      characteristics of the recombinant protein from the three vehicle formulations
      were demonstrated with diffusion cells. Histological and immunohistochemical
      evaluation was performed on biopsies taken on the last day of the experiment.

PMID- 9552445
TI  - A relationship between screen opening and mesh size for standard sieves.

PMID- 9552444
TI  - Cosolvent effects on the gel formation and gel melting transitions of Pluronic
      F127 gels.

PMID- 9552446
TI  - Research in solid dosage forms--an obsolete topic?

PMID- 9552447
TI  - Formulation development of sustained-release hydrophilic matrix tablets of
      zileuton.
AB  - The purpose of this paper was to develop a hydrophilic matrix system for extended
      oral delivery of zileuton, and study the effects of certain formulation,
      processing, and dissolution variables on in vitro drug release. Tablet
      formulations with 60-70% drug and varying release rates were prepared by wet
      granulation using low and medium viscosity grades of hydroxypropylmethocellulose.
      In vitro drug release was evaluated using USP apparatus 1. The in vitro drug
      release from all formulations followed zero-order kinetics and was independent of
      compression force. In general, the release rate decreased with increasing drug
      load and higher polymer concentration or viscosity. High-shear granulation also
      resulted in lower release rate. Accelerated release was observed with increased
      agitation as well as in the dissolution media with higher surfactant
      concentration and/or ionic strength. No stereoselective release from the matrix
      system was observed. The hydrophilic matrix system effectively controlled the in
      vitro release of zileuton. Matrix tablets with desired release rates can be
      prepared by adjusting various formulation and processing parameters. The matrix
      system also has the advantage of simple processing and relatively low cost.

PMID- 9552448
TI  - Preliminary assessment of an image analysis method for the evaluation of
      pharmaceutical coatings.
AB  - This article describes the development and preliminary assessment of an
      innovative image analysis method for the evaluation of pharmaceutical coatings.
      Nonpareils previously hot-melt coated with a red water-soluble dye incorporated
      into polyethylene glycol were employed to develop and evaluate the new method.
      Digital images of batch samples were acquired and transferred to a PC for
      evaluation by image analysis software. Standard deviations generated for the
      optical densities of individual nonpareils in each batch sample were utilized to
      evaluate coating uniformity. Mean optical densities generated for each batch
      sample were used to evaluate the mean coating thickness. Method precision
      determinations, using an average sample size of 221 nonpareils, returned a
      relative standard deviation of 2.47% for coating uniformity and 1.71% for coating
      thickness. The new method is rapid, objective, and relatively inexpensive. It
      proved to be both qualitative and quantitative for coating uniformity,
      qualitative for coating thickness, and maintained a high degree of precision. The
      method can be used independently or in conjunction with other methods to
      eliminate their subjective aspects regarding sample selection.

PMID- 9552449
TI  - The effect of operating and formulation variables on the morphology of spray
      dried protein particles.
AB  - The purpose of this research was to investigate the shape and morphology of
      various spray-dried protein powders as a function of spray-drying conditions and
      protein formulations. A benchtop spray dryer was used to spray dry three model
      proteins in formulation with a sugar or a surfactant. Physical characterizations
      of the powder included morphology (scanning electron microscopy), particle size,
      residual moisture, and X-ray powder diffraction analyses. A significant change in
      particle shape from irregular (e.g., "donut") to spherical was observed as the
      outlet temperature of the dryer was decreased. The drying air outlet temperature
      was shown to depend on various operating parameters and was found to correlate
      with the drying rate of atomized droplets in the drying chamber. The morphology
      of spray-dried protein particles was also affected by formulation. In
      protein:sugar formulations, spray-dried particles exhibited a smooth surface
      regardless of the protein-to-lactose ratio, whereas roughness was observed when
      mannitol was present at > 30% of total solids, due to recrystallization. Protein
      particles containing trehalose at concentrations > 50% were highly agglomerated.
      The presence of surfactant resulted in noticeably smoother, more spherical
      particles. The shape and the morphology of spray-dried powders are affected by
      spray drying conditions and protein formulation. This study provides information
      useful for development of dry proteins for fine powder (e.g., aerosol)
      applications.

PMID- 9552450
TI  - Relating formulation variables to in vitro dissolution using an artificial neural
      network.
AB  - The purpose of this paper was to investigate the effect of several experimental
      variables on the ability of a neural network to predict in vitro dissolution rate
      as a function of product formulation changes. Neural network software was trained
      with sets of hypothetical and experimental data consisting of 4-15 formulations
      with known in vitro drug dissolution profiles and the ability of the trained
      model to recognize patterns was validated against similar formations not used to
      train the neural network. The effect of selected variables, e.g., number of
      hidden-layer nodes and iterations, as well as the use of replicate or mean data
      on the accuracy of the predictions was investigated. The importance of optimizing
      the number of hidden-layer nodes and iterations was demonstrated. The prediction
      error increased for validation data sets that were outside the range of the
      training data set. Accurate predictions were obtained with as few as four
      formulations in the training set, provided the formulations were carefully
      chosen, and the number of formulation variables were small. Also, limiting the
      validation set to one formulation was not sufficient to validate the neural
      network model. Increasing the size of the training set, or replication of the
      input and output data, also provided more accurate predictions. The neural
      network accurately predicted in vitro drug release provided the neural network
      variables were optimized, and the training and validation data sets were
      appropriately selected.

PMID- 9552451
TI  - Physical and chemical properties of DMP 504, a polyalkylammonium-based bile acid
      sequestrant.
AB  - The purpose of this study was to characterize the physicochemical properties of
      DMP 504 and lay the foundation for formulation development. Thermal properties
      were characterized by DSC and TGA and moisture sorption and desorption by TGA.
      The association rate and equilibrium binding capacity of the polymer for a
      prototype bile acid was evaluated using cholic acid, and solid state stability
      was examined at 25 degrees C, 40 degrees C (with and without 5% added water), 60
      degrees C, and 600 foot candles/25 degrees C. The solid state excipient
      compatibility of binary mixtures of DMP 504 and several commonly used
      pharmaceutical excipients was also evaluated. Thermal analysis of the polymer
      showed a glass transition temperature at approximately 95 degrees C and no
      melting point, indicating a highly amorphous macromolecular structure with
      thermal stability up to 250 degrees C. Moisture sorption and desorption isotherms
      at controlled humidity ranging from 11% to 97% RH did not display hysteresis.
      Cholic acid associated with DMP 504 extremely rapidly so that binding was
      essentially complete within 5 min. Scatchard analysis of the equilibrium binding
      of cholic acid to DMP 504 was unconventional, and indicated that the system was
      exhibiting positive cooperative behavior. Modeling the binding curve for a system
      exhibiting cooperative behavior indicated a maximum binding capacity of DMP 504
      for cholic acid in phosphate buffered saline (pH 7.0) of 4.9 mumol/mg, and a
      cooperativity value, P, of 2.2 implying that binding of one molecule promotes the
      binding of additional molecules. DMP 504, a hygroscopic, amorphous cross-linked
      polymer with a tendency to gain or lose moisture with ease, is stable in the
      solid state, either drug substance alone or in presence of excipients, at normal
      storage temperatures and light, and under controlled conditions of humidity.

PMID- 9552452
TI  - Use of chitosan in compressed tablets of diclofenac sodium: inhibition of drug
      release in an acidic environment.
AB  - The purpose of this study was to evaluate the potential utility of chitosan (I)
      in inhibiting diclofenac sodium (II) release in the gastric environment from a
      directly compressible tablet formulation. I, subjected to depolymerization to
      improve its microcrystallinity and subsequent compressibility, was then used to
      prepare tablets of II. A full-factorial design was employed to evaluate the
      effects of degree of N-deacetylation of I, and the pH and ionic strengths, mu, of
      the dissolution media on drug release. Directly compressible tablets were
      prepared from admixtures of 25 mg of II, 174 mg of I of various degrees of N
      deacetylation (74, 87, and 92%), and 1 mg of magnesium stearate. The in vitro
      dissolution studies were performed using aqueous buffers (pHs 1.2, 3.8, and 6.8,
      and mu of approximately 1.0 and 0.1). The slopes of logarithmically transformed
      cumulative percent released-time curves (from t = 0 to t = 5 hr) were compared.
      Analyses of variance performed using SAS indicated that the degree of N
      deacetylation of chitosan significantly affected drug release at pHs 1.2 and 6.8
      (p < 0.0001). An increase in the pH of the dissolution medium resulted in an
      increase in drug release (p < 0.0001). The ionic strength of the dissolution
      medium did not significantly affect drug release at any of the pHs studied (p >
      0.198). Besides the poor aqueous solubility of II, the two factors possibly
      affecting the drug release in the acidic environment were (a) the formation of a
      rate-limiting chitosan gel barrier; and (b) the ionic interaction of II with
      ionized amino groups of I.

PMID- 9552453
TI  - Glass fragility and the stability of pharmaceutical preparations--excipient
      selection.
AB  - The objectives of this study were, first, to calculate the zero mobility
      temperatures, T0, of trehalose and sucrose by the Pikal method from the width of
      the glass transition and compare these to the literature, obtained by enthalpy
      relaxation measurement, and second, to compare the T0 values and physicochemical
      properties of trehalose to those of sucrose in terms of potential to stabilize
      labile actives in the glassy state. Differential scanning calorimetry and
      coulometric Karl-Fischer analysis were used. The glass transition temperatures,
      Tg, for the two carbohydrates at circa 0.7% moisture were 101 degrees C and 64
      degrees C for trehalose and sucrose, respectively. Anhydrous amorphous trehalose
      had a Tg of 116 degrees C. The T0 values were found to be 44 and 3.5 degrees C
      for trehalose and sucrose, respectively. The Tg-T0 value for sucrose was
      compared, and found to be in good agreement with that found by enthalpy
      relaxation measurements. Trehalose was found to be resistant to crystallization
      above the glass temperature. The study supports the validity of the calculation
      method proposed by Pikal for T0. It has been proposed in the literature that T0
      is a better measure of stability than Tg. Trehalose has a significantly higher T0
      than sucrose and thus would work more effectively in stabilizing a labile active.

PMID- 9552454
TI  - Transmucosal delivery of oxytocin to rabbits using a mucoadhesive buccal patch.
AB  - A biocompatible, mucoadhesive buccal patch was evaluated in rabbits for
      transmucosal delivery of peptides. Oxytocin (OT) was incorporated into custom
      coformulations of Carbopol 974P and silicone polymer and the resulting plasma OT
      concentration versus time profiles determined following patch application. For
      comparative purposes, the mean values determined for the elimination half-life
      (t1/2), volume of distribution (Vd), and the total body clearance (CL) following
      intravenous injection of OT were 2.9 +/- 0.2 min, 85.3 +/- 6.7 ml, and 20.4 +/-
      2.03 ml/min, respectively. Following application of oxytocin-loaded mucoadhesive
      patches, plasma OT concentrations remained 20- to 28-fold greater from 0.5 to 3.0
      hr than control animals administered placebo patches. The steady-state plasma OT
      concentration (Css) following application of the buccal patches was 80.6 +/- 15.9
      pg/ml. The lag-time associated with attainment of the Css was 0.45 +/- 0.18 hr.
      Steady-state flux (Jss) of oxytocin in vivo was 139 +/- 36.8 ng/hr/cm2. Based on
      the amount of OT remaining in the patches following removal, the average dose of
      OT released in vivo was 0.27 +/- 0.024 mg with a bioavailability of 0.1%. No
      significant alterations in mucosal histology were observed when underlying mucosa
      to which OT patches had been applied were compared to either control (no patch)
      mucosa or mucosa underneath placebo patches. The mucoadhesive buccal patches were
      easy to apply and remove, nonirritating to tissue, and able to continuously
      deliver a nonapeptide over 3 hr. Based on these preliminary studies, the
      mucoadhesive buccal patches evaluated may represent an improved transmucosal drug
      delivery system for peptides and conventional drug substances.

PMID- 9552455
TI  - Hemolytic and antifungal activity of liposome-entrapped amphotericin B prepared
      by the precipitation method.
AB  - A new method of preparing liposomes containing amphotericin B (AmB) was developed
      with the purpose of reducing the toxicity of AmB without causing a loss in its
      antifungal activity. The procedure involved the precipitation of AmB and egg
      phosphatidylcholine (PC) in phosphate buffered saline (PBS, pH 7.4) or tris
      buffered saline (TBS, pH 7.4) by evaporating methanol and chloroform, which had
      been previously mixed in the buffer solution, at 4 degrees C and 600 mm Hg. The
      in vitro toxicity of the precipitated liposomes containing 3, 6, 9, 12, and 15
      wt% AmB was compared with that of the film-swollen liposomes containing the
      equivalent contents of the drug. The hemolytic ability of the precipitated
      liposomes at 37 degrees C was 50.3% at maximum of the film-swollen liposomes at a
      dose of 30 micrograms AmB/ml, as measured after 17-hr incubation. The significant
      reduction in the hemolysis effect may in fact be attributed to the reduced rate
      of drug release from the precipitated liposomes. The precipitated liposomes were
      multilayered and aggregates of AmB were embedded in the bilayers. These
      aggregates of AmB would be responsible for an intensive positive peak around 330
      nm and reduced toxicity. Despite the decrease in toxicity, the activity of the
      precipitated liposomes against Candida albicans remained almost equipotent to
      that of the film-swollen liposomes. Therefore, liposomes prepared by the
      precipitation method are less toxic but equally as active.

PMID- 9552456
TI  - Studies on diffusion in alginate gels. II. Effect of acid and subsequent re
      exposure to calcium on the diffusion of caffeine and theophylline in alginate gel
      films.
AB  - The aim of this research was to investigate the effect of acid exposure and
      calcium re-exposure on the diffusion of caffeine and theophylline through calcium
      alginate gel films. Diffusion was measured using side-by-side glass cells, before
      and after the films were exposed to simulated gastric fluid (SGF) USP minus
      pepsin. The permeability increased by about 15-fold for theophylline and 48-fold
      for caffeine after 5 min SGF exposure. There was no significant further increase
      by prolonging the exposure time to 4 hr. The diffusion of both drugs was less
      than through alginate gel films that were not cross-linked with calcium but were
      gelled in SGF. Treatment of the calcium alginate gel films with SGF depleted the
      films of all of their calcium content. Calcium alginate gel films that were
      exposed to SGF for a constant period of 15 min, were re-exposed to 0.34 M calcium
      chloride solution for periods up to 24 hr. The calcium content returned to 80% of
      the level in the original calcium alginate films and diffusion was reduced, but
      not to the level that was observed in the original calcium alginate films. It was
      concluded that the effect of SGF on calcium alginate was very rapid and that the
      increase in drug diffusion observed was probably due to removal of calcium from
      the gel. It was also concluded that the original diffusion properties and calcium
      content could only be partially regenerated by re-exposing the acid-exposed films
      to calcium chloride.

PMID- 9552457
TI  - Solubilization of various benzodiazepines for intranasal administration, a pilot
      study.

PMID- 9552458
TI  - Is it necessary to take small blend samples to assess drug uniformity?

PMID- 9552459
TI  - Accelerated conditions for stability assessment of bulk and formulated cefaclor
      monohydrate.
AB  - The stability of cefaclor monohydrate drug substance and formulated products was
      studied under accelerated conditions in order to provide a rapid indication of
      differences that might result from a change in manufacturing process or source of
      the sample. The USP stability-indicating related substances assay was used to
      assess the extent of sample degradation. An Arrhenius study of drug substance
      stability from 45 to 70 degrees C predicted a degradation rate consistent with
      that observed in room-temperature studies. Qualitative degradation profiles of
      samples held at 65 degrees C for 2 weeks were also very similar to those of
      samples held at room temperature for 2 years. Based on these results, additional
      studies were conducted at 65 degrees C for 2 weeks on drug substance and
      formulated product samples. Stability differences were observed among some
      capsule formulations that had also exhibited real time differences. In some
      studies, rapid degradation after 5 days was observed at 65 degrees C followed by
      a slower rate from 5 to 15 days. Similar behavior was observed for cefaclor
      monohydrate containing high amounts of amorphous cefaclor, suggesting that
      differences in amorphous content could be an explanation for stability
      differences observed in various samples. The accelerated conditions were shown to
      differentiate samples and can provide a rapid indication of relative stability.

PMID- 9552460
TI  - The effect of composition on the tableting indices of binary powder mixtures.
AB  - The purpose of this study was to investigate the effect of the composition of a
      binary powder mixture on the bonding index, the brittle fracture index, and the
      strain index, as defined by Hiestand. The studies involved tensile strength and
      dynamic indentation hardness determinations of square compacts, the solid
      fractions of which were 0.83. The mixtures were such that both components
      consolidated by plastic deformation, both components consolidated by brittle
      fracture, or one component was brittle while the other was plastic. The measured
      quantities were then used to compute the bonding index, the brittle fracture
      index, and the strain index. The bonding indices and tensile strengths of the
      individual plastic materials were greater than those of the individual brittle
      materials. It was concluded that the bonding indices were linearly related to
      composition when both materials consolidated by the same mechanism. It was
      further concluded that the bonding indices were related to compact composition by
      a second-degree polynomial equation for mixtures with one brittle and one plastic
      component. This latter relationship was consistent for four pairs of components.

PMID- 9552461
TI  - Microencapsulation of antimicrobial ceftiofur drugs.
AB  - Polymeric microparticles containing two ceftiofur salts as antimicrobial agents
      for intramammary application in dry cows were prepared by modified o/w-solvent
      evaporation methods (dispersion or cosolvent method) or by a w/o/w-multiple
      emulsion solvent evaporation method. The microspheres were characterized with
      respect to drug loading, drug release, and morphological properties. The three
      methods resulted in high encapsulation efficiencies. The choice of organic
      solvent/solvent mixture strongly affected the structure of the microparticles;
      both matrix and reservoir-type structures with different porosities were
      obtained. Scaling up to larger batch sizes resulted in microspheres with a faster
      drug release. The addition of water-miscible cosolvents to the water-immiscible
      polymer solution allowed the preparation of microparticles from a drug solution
      rather than a drug dispersion. Microparticles prepared by the cosolvent method
      could be separated after shorter time intervals from the aqueous phase; the
      microspheres had a denser matrix with finely dispersed drug crystals and a slower
      drug release when compared with microspheres prepared by the dispersion method,
      which had a more porous structure with larger embedded drug crystals. The
      cosolvent and dispersion methods present a simple alternative to the w/o/w
      solvent evaporation method for the encapsulation of water-soluble drugs with an
      external water phase.

PMID- 9552462
TI  - The formation of lactose plugs for hard shell capsule fills.
AB  - The purpose of this investigation was to study the effects of lubricant
      concentration, dosator pressure, and dosator piston height on the properties of
      lactose plugs. An apparatus designed to simulate Macofar 13/2 capsule filling
      equipment was used, and the relationship between the variables and the responses
      was established using a Box-Behnken three-factor, three-level experimental design
      followed by multiple regression. Plug porosity, both under compression and after
      ejection, was found to be dependent on dosator pressure. Plug weight and length
      were dependent on dosator piston height, and uniformity of plug weight was
      independent of all the factors studied. Plug ejection pressure was dependent on
      dosator pressure and dosator piston height, even when ejection pressure was
      corrected for changes in plug length. Lubricant concentration had no significant
      effect on any plug property, and it must be concluded that 0.5% magnesium
      stearate provides adequate lubrication for lactose plugs. No interaction between
      variables was noted, and values of the variables raised to the power 2 had no
      significant effect, permitting a simplified experimental design to be adopted for
      future work.

PMID- 9552463
TI  - The effect of polyvinylpyrrolidine on the stability of taurolidine.
AB  - In an aqueous solution, taurolidine reversibly degrades to taurultam,
      hydroxymethyltaurultam, taurineamide, and formaldehyde. The objectives of this
      research were to investigate the mechanism of polyvinylpyrrolidine (PVP)-induced
      taurolidine stabilization by measuring the effect of PVP on the rate and extent
      of formaldehyde release from taurolidine and its decomposition products, the
      ionization of taurineamide, and the NMR and FT-IR spectra of taurineamide. PVP
      was found to a) increase the rate constant for taurultam formation from
      taurineamide and formaldehyde, b) decrease the apparent pKa of taurineamide, and
      c) alter the NMR and FT-IR taurineamide spectra. The effect of PVP on the
      stability of taurolidine was to increase the stability of its primary degradation
      product, taurultam, which, in turn increased taurolidine stability because
      taurultam was reversibly formed from taurolidine. Furthermore, the increased
      stability of taurultam in acidic, aqueous PVP solutions was due to an increased
      rate of taurultam formation from its primary degradation products: taurineamide
      and formaldehyde. The rate constant for taurultam formation increased three-fold
      in the presence of 5% PVP. The rate increase was caused by the interaction of
      unprotonated taurineamide with PVP. The estimated taurineamide-PVP association
      constant was 1800 M-1. This interaction decreased the concentration of
      unreactive/protonated taurineamide while increasing the concentration of
      unprotonated/associated substrate which was found to be fivefold less reactive
      than the free/unprotonated amine.

PMID- 9552464
TI  - Optimization of aqueous-based film coating of tablets performed by a side-vented
      pan-coating system.
AB  - The purpose of this research was to characterize the aqueous-based
      hydroxypropylmethylcellulose (HPMC) film coating of tablets utilizing a
      laboratory-scale side-vented pan-coating apparatus (Thai coater). The process and
      apparatus parameters of potential importance with respect to the final film
      quality were evaluated by using fractional factorial design (2(6-2)IV) and the
      process was optimized using response surface methodology (central composite
      design). Rotating speed of the pan was identified as a major parameter with
      respect to film thickness (weight increase; p < 0.05) and breaking strength (p <
      0.05) of the aqueous HPMC film-coated tablets. Increasing the rotating speed from
      5 rpm to 10 rpm resulted in a mean relative change of -43.9% and 2.4% of film
      thickness (weight increase) and breaking strength, respectively. As expected,
      inlet air temperature significantly affected the moisture content of the final
      film-coated tablets (p < 0.01) and the film thickness (weight increase; p <
      0.05), but the effects on the other responses studied were minimal or negligible.
      Pneumatic spraying pressure and position of the spray gun (excluding angle of the
      gun) did not affect the responses studied. The process parameters relevant to a
      side-vented pan-coating process can be identified (by fractional factorial
      design) and, consequently, optimized (by central composite design) by using the
      factorial design approach.

PMID- 9552465
TI  - Optimization of sustained-release tablet formulations: a four-component mixture
      experiment.
AB  - Sustained-release tablet formulations containing chlorpheniramine maleate were
      prepared using a mixture of two hydrophilic gums, gamma-carrageenan and cross
      linked carboxymethylcellulose sodium, and two filler materials, alpha-lactose
      monohydrate and dibasic calcium phosphate in different ratios. The objective of
      the experiment was to find an optimum formulation with the most desirable
      properties. In order to achieve this, the matrices were evaluated for the time
      taken to release 80% drug (t80), the release exponent (n), and the crushing
      strength (h). Several formulations produced near zero-order release of the model
      drug over a time period of up to 10 hr. Response surface plots for the three
      dependent variables were generated over the experimental region. the effect of
      different levels of the components on the response variables was thus visualized.
      Upon superimposition of the plots it was possible to graphically find a region
      where the responses were in an optimum range of values. To pinpoint the best
      formulation, a simultaneous optimum point within this region was located by
      arbitrarily defining optimum values for each of the responses and using a multi
      objective function that combined the three response variables. The observed
      response variables of the optimum formulation were in good agreement with the
      predicted values.

PMID- 9552466
TI  - Enhancement and modification of etoposide release from crospovidone particles
      loaded with oil-surfactant blends.
AB  - A novel solid formulation for oral delivery of pH-sensitive, scarcely water
      soluble etoposide has been designed, characterized, and tested in vitro. The
      purpose of this study was to assess the performance of the new dosage forms, in
      comparison to marketed, liquid-filled capsules. The solid formulation was
      developed by grinding the drug with a cross-linked polymeric carrier
      (crospovidone) under controlled process conditions (mechano-physical drug
      activation), and subsequently incorporating selected oil/surfactant (o/s) blends
      into the polymer particles. Physicochemical characterization (thermal analysis,
      drug dissolution kinetics, drug o/w partition studies) provided information on
      drug-polymer interaction at the solid state, and on the formulation performance
      in vitro, resulting in the enhancement and modification of the etoposide
      solubilization process. DSC thermograms showed the amorphous or nanocrystalline
      state of etoposide within the carrier, as indicated by the shifting of DSC peaks
      (delta T > -10 degrees C). Solubility kinetics of etoposide in oversaturation
      conditions were strongly affected by the chemical nature of the vehicle used:
      short-chain triglycerides afforded drug concentrations well above 600 micrograms
      ml-1 for more than 3 hr, versus a drug equilibrium solubility of approximately
      150 micrograms ml-1. Drug dissolution curves under sink conditions were
      superimposable to those of liquid-filled capsules available on the market
      (Vepesid 50, Bristol-Myers Squibb), yielding 100% drug release in 10 min. The oil
      phase/water partition coefficient of etoposide (P) was affected by the surfactant
      concentration. The biphasic trend observed in P values suggested a dual mechanism
      in drug release from polymeric particles: the presence of oily vehicles and
      surfactants in the formulation could create, upon release, a favorable
      environment to sustain etoposide dissolution, slowing down drug reprecipitation.
      Such solid formulation could be considered equivalent, in vitro, to the current
      marketed product.

PMID- 9552467
TI  - Controlled-release tablet matrices from carrageenans: compression and dissolution
      studies.
AB  - This study investigates the potential of two commercial carrageenans, Gelcarin GP
      379 (iota-carrageenan) and Viscarin GP-209 (lambda-carrageenan) to be used for
      the preparation of controlled-release tablet matrices. Tablets were compressed on
      an instrumented Stokes single punch machine and compression characteristics of
      the carrageenans were analyzed. Heckel plots using out-of-die tablet densities
      were linear with calculated yield pressures of 81.3 MPa and 105.2 MPa for iota-
      and lambda-carrageenan, respectively. Drug release from tablet formulations that
      contained equal amounts of the two carrageenans had near zero-order release
      profiles. There was little or no effect of tablet compression pressure on the
      drug release profiles from 70 to 175 MPa. As drug loading was increased from 5 to
      20%, the diffusional exponent decreased from 1.056 to 0.678. Thirty percent drug
      loading resulted in breakup of tablets during dissolution and departure from zero
      order release. Multiple regression analysis was used to predict the time for 50%
      release as a function of the concentration of the two carrageenans and a third
      filler material, microcrystalline cellulose. Predicted values were in good
      agreement with observed values and R2 for the final cubic model was 0.9984.

PMID- 9552468
TI  - Characterization of frozen glucose solutions.
AB  - Reducing sugars may be used as additives in freeze-dried formulations. The
      purpose of this study is to examine the effect of freezing on nonequilibrated
      glucose solutions using FT-Raman spectroscopy. The methods used solutions freshly
      prepared from either alpha- or beta-crystalline glucose, frozen at different time
      intervals after dissolution. Solutions frozen immediately after dissolution
      showed peaks in the anomeric region of the spectrum characteristic of those
      observed for the parent crystalline form. No change occurred in these spectra
      after 24 hr in the frozen state. Solutions prepared from either alpha- or beta
      crystalline glucose and left for 24 hr at room temperature before freezing showed
      the presence of both anomers. The glass transition temperature of maximally
      freeze-concentrated solutions of beta-glucose, frozen immediately after
      dissolution, was found to be approximately 3 degrees C lower than for solutions
      prepared from alpha-glucose. Freezing appears to halt the interconversion of
      glucose anomers, enabling the formation of predominantly alpha- or beta-frozen
      solutions which exhibit different properties. Freezing of nonequilibrated
      solutions of reducing sugars may lead to variation in the properties of freeze
      dried formulations.

PMID- 9552469
TI  - Physicochemical characterizations of piroxicam-poloxamer solid dispersion.
AB  - To develop an efficient topical delivery system for piroxicam using poloxamer gel
      formulation, physicochemical behavior of piroxicam in poloxamer was studied. The
      gelling property of poloxamer and the solubility of piroxicam in the poloxamer
      were investigated. The interaction between piroxicam and poloxamer was studied by
      x-ray diffractometry (XRD), infrared (IR) spectroscopy and differential thermal
      analysis (DTA) with a solid dispersion, coprecipitate, or physical mixture.
      Poloxamer 407 solutions showed the property of a gel when the concentration was
      higher than 15% (w/w) and poloxamer 407 increased the aqueous solubility of
      piroxicam by about 11-fold at the concentration of 22.5% (w/w). The results of
      XRD did not show the crystalline from of piroxicam in the solid dispersion and
      results of IR spectroscopic analysis showed an association between functional
      groups of piroxicam and poloxamer.

PMID- 9552470
TI  - Stability of Octastatin, a somatostatin analog cyclic octapeptide, in aqueous
      solution.
AB  - In this study, the degradation of Octastatin, a cyclic octapeptide analog of
      somatostatin, was examined as a function of pH, temperature, buffer, and ionic
      strength by reversed-phase gradient high-performance liquid chromatography.
      Degradation of Octastatin followed a first-order kinetics. Various buffer species
      such as acetate, ammonium acetate, citrate, glutamate, phosphate, and borate
      showed differing effects on the degradation of the octapeptide. Good stability
      was found in glutamate and acetate buffer of pH 4.0. Degradation of Octastatin
      was greater in citrate- or phosphate-containing buffers than in glutamate or
      acetate buffers. With phosphate buffer, higher buffer concentration caused
      greater degradation, while in acetate buffer, the effect of buffer concentration
      and ionic strength was negligible. In addition, the degradation of Octastatin was
      markedly inhibited by increasing the concentration of glutamate buffer. This
      study allows the prediction of good stability in acetate buffer (0.01 M, pH 4.0)
      with a t90% of 84.1 days at 20 degrees C.

PMID- 9552471
TI  - Need for polishing of new sets of tooling.

PMID- 9552472
TI  - Chitosan-mediated transfection of HeLa cells.

PMID- 9552479
TI  - Historical perspective.
AB  - Development of the first percutaneous catheters for local delivery is described.
      Understanding of the mechanisms by which circulating materials gain entrance to
      the artery wall, and the importance of hypertension in accelerating that process
      were crucial to the conceptual basis of these devices. The double balloon
      catheter and the porous balloon catheter were systematically studied to quantify
      the local pressure-wall penetration relationship. Designs for many new catheters
      that claim advantage over early models require similar systematic demonstration
      of their performance with normal and diseased arteries. Only in this way can this
      promising new technique become a clinical advance against human vascular disease.

PMID- 9552480
TI  - Rationale for local drug delivery.
AB  - Although advances during the last decade have transformed the management of
      coronary artery disease, deficiencies in our understanding of the basic processes
      of arterial thrombosis and restenosis after percutaneous intervention continue to
      present major challenges to their prevention. While coronary stenting has in
      selected cases provided the first effective approach to the problem of
      restenosis, new devices such as atherectomy have largely proven ineffective in
      this field. Similarly, despite evidence that many pharmacological agents reduce
      neointimal hyperplasia in experimental models, in clinical trials these agents
      have failed to attenuate the restenotic process. This may reflect patients'
      inability to tolerate the high systemic drug concentrations required to achieve
      adequate levels for sufficient time at the target site, necessitating a shift in
      the focus of therapeutic agents for the prevention of thrombosis and restenosis
      to local or site-specific delivery. The major advantage that local drug delivery
      may potentially provide is the ability to achieve high and sustained local
      concentrations of drug without large systemic doses, thus minimizing systemic
      toxicity.

PMID- 9552481
TI  - Mechanisms of delivery and local drug delivery technologies.
AB  - Therapy of atherosclerotic vascular disease and neointimal hyperplasia after
      percutaneous interventions remain enigmatic. Despite new interventional devices,
      we have not altered the underlying pathological process. New devices are under
      development that offer the opportunity to deliver high concentrations of
      therapeutic agents directly to the diseased segment. The devices fall into three
      major mechanisms of delivery (1) diffusion, (2) infusion under pressure and (3)
      mechanical delivery. Diffusion catheters are atraumatic but require prolonged
      exposures in excess of 20 min while the pressurized infusion and mechanical
      catheters are more traumatic. Additionally, each system will need to be
      characterized with respect to efficiency of delivery with each agent used. The
      clinical opportunity for site-specific treatment of vascular disease is rapidly
      approaching. In the near future we will be able to open a narrowed vessel and
      also apply some agent into the lesion to facilitate healing.

PMID- 9552482
TI  - Double balloon catheter.

PMID- 9552483
TI  - Microporous infusion catheter.

PMID- 9552484
TI  - Dual balloon catheter.

PMID- 9552485
TI  - Multichannel balloon catheter.

PMID- 9552486
TI  - Infusion sleeve catheter.

PMID- 9552487
TI  - Coil balloon catheter.

PMID- 9552488
TI  - Iontophoretic drug delivery system.

PMID- 9552489
TI  - Nipple balloon catheter.

PMID- 9552490
TI  - Needle injection catheter.

PMID- 9552491
TI  - Hydrogel-coated balloon catheter.

PMID- 9552492
TI  - A polymer-metal composite stent.

PMID- 9552493
TI  - Microspheres.

PMID- 9552494
TI  - Use of local drug delivery for treating intracoronary thrombus and thrombus
      containing stenoses.
AB  - The local delivery of thrombolytic agents directly to the site of intracoronary
      thrombus using catheter-based technology is a new technique for treating
      intraluminal clot and thrombus-containing stenoses that is currently under active
      investigation. The theoretic mechanism of thrombolysis underlying this approach
      involves the 'trapping' of thrombus in an environment of high thrombolytic drug
      concentration, mechanical disruption of intraluminal clot by the drug delivery
      catheter itself, and intramural deposition of lytic agents with the creation of a
      drug reservoir that may provide for prolonged local thrombolysis. To date, animal
      studies with five local drug delivery catheters have documented successful
      intramural deposition of thrombolytic agents at balloon angioplasty sites. Three
      of these devices have also been successfully used in patients to treat
      intracoronary thrombus, with preliminary results suggesting that thrombolysis can
      be achieved using much lower doses of lytic agents than are employed in standard
      infusion protocols and with low complication rates. These preliminary
      observations will be studied further in two multicentre randomized protocols
      comparing local thrombolysis with standard techniques for treating intracoronary
      thrombus.

PMID- 9552495
TI  - Wall passivation for unstable angina.
AB  - The disruption of an atherosclerotic plaque in a coronary artery, appears to be
      fundamental for the development of arterial thrombosis and resultant ischaemia.
      Platelets play a central role in the pathogenesis of unstable angina; they can
      aggregate and cause mechanical obstruction if large enough. In addition, they can
      lead to fibrin deposition and extension of the thrombus. The fundamental goal in
      the treatment of unstable angina is to control the acute disease process that
      leads to vascular occlusion. In addition to the currently available
      pharmacological agents used to treat unstable angina, newer agents such as the
      direct thrombin inhibitors and the glycoprotein IIb/IIIa receptor antagonists may
      be more effective in achieving 'passivation'. This article summarizes the role of
      the vessel wall and its interaction with platelets in arterial thrombosis. The
      different pharmacological approaches used in achieving passivation of platelets
      in unstable angina are described.

PMID- 9552496
TI  - Use of locally delivered conventional drug therapies.
AB  - Coronary artery restenosis remains the major limitation of balloon angioplasty
      and occurs in 30-50% of initially successful procedures. Our current
      understanding of pathophysiology of restenosis suggests that it involves three
      inter-related phases; (1) acute effects of thrombosis, (2) neointimal
      proliferation, and (3) acute recoil and chronic remodelling. In an attempt to
      prevent vessel restenosis both systemic and site-specific pharmacotherapy have
      been investigated. Although successful in animal models, systemically
      administered pharmacological agents for the prevention of restenosis in humans
      have not been effective. The local administration of compounds such as heparin,
      anti-thrombin agents, colchicine, angiopeptin, antineoplastic agents, calcium
      antagonists, nitrates, forskolin, cytochalasin B, protein kinase inhibitors and
      dexamethasone have been shown to reduce neointimal formation in animal models of
      restenosis. Clinical trials have demonstrated the feasibility of the local
      administration of heparin using both InfusaSleeve and Dispatch drug delivery
      catheters. Preliminary results on long-term prevention of restenosis by heparin
      appear promising using the Dispatch delivery device. In addition, a multicentre
      trial investigating the effectiveness of cytochalasin B delivered using the
      Microporous Infusion Catheter for the prevention of restenosis is currently
      underway. Rapid progress in our understanding of the complex pathophysiology of
      restenosis and the development of more effective pharmacological agents and
      atraumatic site specific delivery modalities ensure a promising future for local
      delivery strategies.

PMID- 9552497
TI  - Genetic therapy.
AB  - Vascular gene transfer is the introduction of foreign DNA into host cells within
      the vessel wall. Expression of recombinant genes within vascular cells has been
      demonstrated in normal, injured and atherosclerotic arteries. Transfer of genes
      with biological activity has provided insights into the role of specific genes in
      normal and pathological states. The development of gene transfer as a form of
      vascular therapy will require safe and effective vectors and intravascular
      delivery systems. Viral and non-viral vectors and several delivery catheters are
      being evaluated to determine their clinical applicability. The current
      applications of vascular gene transfer to cardiovascular diseases are the
      prevention of restenosis following arterial injury and induction of angiogenesis
      in occlusive vascular disease.

PMID- 9552498
TI  - Vascular applications of human gene therapy.
AB  - Complexing recombinant DNA with cationic liposomes is a convenient means of
      introducing foreign genes into cells (lipofection) and could potentially form the
      basis for genetically modifying diseased blood vessels in patients. The mechanism
      of lipofection is incompletely understood but it is recognized that the degree of
      successful gene transfer is highly dependent on cell type. We have transfected
      primary cultures of human vascular smooth muscle cells with a plasmid expressing
      either firefly luciferase (Luc) or nuclear-localized beta-galactosidase (NL-beta
      gal). Cells were derived from either normal human internal mammary arteries,
      fragments of primary atherosclerotic plaque, or fragments of restenotic lesion.
      Concurrent lipofection of rabbit vascular smooth muscle cells and NIH 3T3 cells
      was performed as well. Compared to NIH 3T3 cells, expression in human vascular
      smooth muscle cells was markedly reduced: in cells derived from internal mammary
      artery, Luc expression, normalized for protein content, was 123-fold lower than
      in NIH 3T3 cells, while the proportion of cells expressing NL-beta-gal was 30
      fold lower. Luc expression in cells derived from restenotic tissue was
      significantly greater than from cells derived from primary plaque. Within a given
      population of cells, the mitotic index of cells expressing the recombinant gene
      was significantly higher than the mitotic index for the total population of cells
      (p < 0.05). Finally, cotransfection experiments, in which lipofection of smooth
      muscle cells was performed using genes for NL-beta-gal and for human growth
      hormone, showed that among positive transfectants, a high proportion of cells (23
      36%) co-expressed both genes. Thus, the efficiency of successful lipofection in
      human vascular smooth muscle cells in vitro is low. Transfection appears to be
      preferentially facilitated in cells derived from restenotic tissue and specific
      properties of smooth muscle cells, including growth rates, appear to be critical
      for successful transfection. Further elucidation of cell properties that promote
      transfection is required to augment the efficiency of liposome-mediated gene
      transfer in human vascular cells.

PMID- 9552499
TI  - Electro-encapsulating drugs within blood platelets: local delivery to injured
      arteries during angioplasty.
AB  - Prostacyclins (PGl2) inhibit platelet-platelet interactions at concentrations
      that do not affect platelet adhesion to collagen and other arterial
      subendothelial structures exposed during injury. Such compounds can be
      encapsulated within platelets by reversible electroporation and, using the
      platelet's natural haemostatic propensity, they can be targeted to injured
      vessels in vivo. In rat (aorta), rabbit (ileofemoral) and pig (carotid)
      angioplasty models, autologous platelets, electro-loaded with the stable
      prostacyclin iloprost and given intravenously after balloon overstretch injury,
      substantially reduced platelet deposition at the lesion site as compared with
      control platelets. In the pig model, when the drug-loaded platelets were
      delivered directly to the injury site during angioplasty via a double balloon
      delivery catheter, platelet deposition was restricted to monolayer coverage (>
      80% reduction compared with controls). Candidate antiproliferative drugs (for co
      encapsulating with iloprost) are being investigated in order to develop a
      combined antithrombotic/antirestenosis strategy for use during angioplasty and
      thrombolysis procedures. Autologous platelets as drug-targeting vehicles should
      obviate many of the immunological, toxicological and biodegradability concerns
      inherent in the use of other drug transport vectors such as antibodies, viruses,
      liposomes and synthetic polymer microcapsules.

PMID- 9552500
TI  - Polymeric endoluminal gel paving: therapeutic hydrogel barriers and sustained
      drug delivery depots for local arterial wall biomanipulation.
AB  - Polymeric endoluminal paving is a process in which biodegradable polymers may be
      locally applied percutaneously to blood vessels as endoluminal liners,
      resurfacing or 'paving', the underlying vascular wall. Depending upon the type of
      polymer selected, endoluminal polymer layers may function as wall supports,
      barriers, therapeutic biomaterials or depots for local sustained drug delivery.
      In the original description of the paving process, that is solid paving,
      structural polymers were utilized. In this article a second form of paving--gel
      paving is described. In this process, hydrogel polymers are locally applied or
      polymerized on vascular endoluminal surfaces. Endoluminal hydrogel layers have
      been demonstrated to function as physical non-pharmacological barriers limiting
      cell and protein deposition and effectively reducing underlying arterial wall
      thrombogenicity. Hydrogel paving layers also provide a means for prolonged local
      arterial wall drug delivery. In this report an update on gel paving is provided.
      The overall process of polymeric endoluminal paving is initially reviewed. Gel
      paving and the rationale for this approach is described. Both thermoreversible as
      well as photopolymerizable PEG-lactide hydrogel paving systems are outlined.
      Recent experimental studies with gel paving examining polymer application,
      haemocompatability and endoluminal surface thromboprotection, effects on post
      injury neointimal thickening and local drug delivery, are then reviewed. Finally,
      the role of gel paving in future approaches to vascular therapy is discussed.

PMID- 9552501
TI  - Laser angioplasty: historical perspective.
AB  - Serious interest in laser angioplasty began in the early 1980s in an attempt to
      solve two of the primary limitations of balloon angioplasty, recanalization and
      restenosis. By demonstrating the ability of laser irradiation to vaporize
      atherosclerotic tissue, it was logical to hypothesize that this powerful tool may
      allow recanalization of lesions that could not be crossed by conventional
      guidewire and balloon technology. With refinements in laser fibreoptics and
      catheter delivery systems, several laser systems were approved for clinical use
      as recanalization devices in both peripheral and coronary arteries. However, the
      requirement to follow laser angioplasty with conventional balloon angioplasty in
      the majority of cases and the lack of an effect of laser tissue removal
      (debulking) on restenosis has limited a broader acceptance of this technology.
      Perhaps improved techniques discussed later in this series such as saline
      infusion and better fibreoptic-lens systems will allow laser angioplasty to offer
      a true niche in interventional cardiology.

PMID- 9552502
TI  - Fundamental laser-tissue interactions.
AB  - Pulsed xenon chloride excimer and holmium laser-tissue interaction is primarily
      based on tissue water vaporization. Consequently, each ablative laser pulse
      produces a rapidly expanding and imploding vapour bubble in blood or the target
      tissue. In experimental studies, explosive water vaporization is the major
      mechanical cause of observed tissue dissections. By reduction of the induced
      bubble volume, a reduction in experimentally and clinically observed dissections
      after coronary excimer laser angioplasty is to be expected. This reduction of
      mechanical damage, however, in combination with efficient and substantial plaque
      debulking is the major challenge in the development of laser angioplasty.

PMID- 9552503
TI  - Clinical results with excimer laser coronary angioplasty.
AB  - This comprehensive review of randomized trials and registry reports makes several
      assertions about the clinical usefulness of excimer laser angioplasty. First,
      refinements in patient selection and excimer laser technique have resulted in
      improved procedural outcome. Second, the overall rates of clinical success for
      excimer laser angioplasty are approximately 90%, major and minor complications
      6%, and vessel perforation 1%. Third, superior success rates are achieved for
      saphenous vein graft lesions, ostial stenoses and total occlusions, but decreased
      success rates are obtained for bifurcation, calcified and thrombus-containing
      lesions. The routine use of saline infusion during excimer laser angioplasty and
      careful evaluation of this therapy for new indications such as in-stent
      restenosis will increase the usefulness of excimer laser angioplasty in
      interventional cardiovascular medicine.

PMID- 9552504
TI  - Saline infusion in excimer laser coronary angioplasty.
AB  - While the effects of high-intensity laser energy on tissue were studied early in
      the development of the laser, the interactions of laser radiation with immersion
      media have been the subject of more recent investigations. Prompted by reports of
      severe, morphologically unusual dissections occurring during 308 nm excimer laser
      angioplasty, several investigators have now demonstrated that both blood
      (haemoglobin) and angiographic contrast media strongly absorb excimer laser light
      at 308 nm. Upon absorption, this light energy is converted into rapidly expanding
      and imploding cavitation bubbles that generate intense pressure pulses.
      Subsequently, several techniques to remove contrast and dilute blood in the
      ablation field were evaluated. The application of saline infusion has resulted in
      improvements in both angiographic and clinical outcomes. The purpose of this
      paper is to review the development and application of the technique of saline
      infusion in the clinical practice of excimer laser coronary angioplasty.

PMID- 9552505
TI  - Homogeneous light distribution to reduce vessel trauma during excimer laser
      angioplasty.
AB  - Excimer laser coronary angioplasty (ELCA) is associated with vascular damage,
      caused by rapidly expanding water vapour bubbles and accumulation of insoluble
      gas. The size of the rapidly expanding bubbles and the volume of gas can be
      reduced by decreasing the laser pulse energy density. However, using current
      multifibre catheters, penetration through porcine aortic tissue was found to be
      impossible at energy densities < or = 45 mJ/mm2. By contrast, by employing a 660
      microns bare fibre it was observed that efficient tissue crossing was possible at
      12 mJ/mm2, with considerable reduction of the rapidly expanding bubble volume and
      insoluble gas production. We attribute this efficient tissue penetration at low
      energy densities to the absence of 'dead space' in the homogeneous light
      distribution (HLD) at the fibre tip. Accordingly we hypothesize the ELCA
      performed at lower energy densities may result in less mechanical trauma to the
      vessel wall when compared with ELCA using current multifibre catheters.

PMID- 9552506
TI  - Holmium laser angioplasty.
AB  - The investigational solid-state, pulsed-wave, mid-infrared (2.1 microns)
      holmium:YAG laser can be applied for plaque ablation and thrombus dissolution. A
      multicentre study reports 87% laser success and 94% final procedural success. It
      has established the safety and efficacy of this laser in ischaemic syndromes and
      acute myocardial infarction treating lesions considered 'not ideal' for balloon
      angioplasty. These include thrombotic occlusions, total occlusions, calcified
      obstructions, de novo and restenosis lesions within native coronary arteries and
      saphenous vein grafts. Unfortunately, the laser does not significantly reduce
      restenosis rate. Processes related to laser-tissue interactions such as gas
      vapour formation and generation of acoustic waves with tremendous intraplaque
      pressures mandate application of appropriate lasing technique to ensure clinical
      success.

PMID- 9552507
TI  - The laser guidewire experience: 'crossing the Rubicon'.
AB  - Despite continued improvements in mechanical hardware for coronary angioplasty,
      chronic total occlusions (CTO) remain a true challenge in the field of
      interventional cardiology. Therefore, new guidewire technology, which made use of
      the unique forward debulking properties of excimer laser light, was designed and
      introduced into clinical practice in 1993. After an initial pilot-study phase, a
      European Multicenter Surveillance Study was initiated to evaluate the performance
      of the new laser guidewire. A short overview is given of the incidence of CTO.
      The limitations of the percutaneous treatment with various mechanical guidewires
      and the clinical and angiographic follow-up of CTO are discussed. Furthermore,
      the initial experience with the laser guidewire during the pilot-phase and
      preliminary results of the European Multicenter Surveillance Study are presented.
      At the introduction of yet another new (and costly) device, the key question is:
      'Yes, but does it allow us to expand the battle field of interventional
      cardiology?'

PMID- 9552508
TI  - Molecular strategies to inhibit restenosis: modulation of the vascular myocyte
      phenotype.
AB  - The transduction of vascular myocytes with exogenous genetic material will be a
      common feature of many gene-based therapies for cardiovascular disorders.
      Therefore, the successful application of cardiovascular gene therapy will require
      a thorough understanding of the molecular biology of the smooth muscle cell. Of
      key importance are the transcriptional regulatory events that coordinate the de
      differentiation and proliferation of myocytes in response to vascular injury. The
      goal of this review is to highlight what is known about the regulators of
      vascular myocyte transcription that may serve as candidate genes for the
      development of genetic strategies to manage postinterventional restenosis.

PMID- 9552509
TI  - Gene transfer approaches to the regulation of vascular cell proliferation.
AB  - Considerable progress has been made in identifying potential targets for treating
      vascular proliferative diseases. In this review, we discuss gene transfer
      approaches to regulating smooth muscle cell proliferation after vascular injury
      using the cell cycle specific proteins, p21, delta Rb and HSV-tk. Results from
      these studies suggest that replicating smooth muscle cells and macrophages are
      inhibited in vivo in several animal models of restenosis, including
      hyperlipidaemic vessels. Identification of appropriate vascular diseases and
      improvements in gene delivery and vectors will require careful optimization in
      order to develop effective molecular therapies for human vascular diseases.

PMID- 9552510
TI  - Gene therapy for vascular proliferative disorders.
AB  - Despite major advances in interventional techniques in recent years, restenosis
      remains an important late complication of percutaneous revascularization
      procedures. Vascular smooth muscle cell proliferation after arterial injury plays
      an important role in the pathogenesis of restenosis. Major progress has been made
      recently in elucidating the cellular and molecular mechanisms underlying this
      proliferative response. This in turn has led to the development of novel, gene
      based approaches for the treatment and prevention of restenosis as well as other
      vascular proliferative disorders. Included among these are somatic gene therapy
      the ability to introduce and express recombinant genes in non-germ-line cells of
      a recipient organism in vivo. This article reviews specific genetic approaches
      that have recently been developed for the treatment of vascular proliferative
      disorders such as restenosis, focusing on the use of adenovirus-mediated arterial
      gene transfer strategies designed to suppress the vascular smooth muscle cell
      proliferative response associated with these diseases.

PMID- 9552511
TI  - Apoptosis in vascular disease: opportunities for genetic therapeutic
      intervention.
AB  - Apoptosis functions to efficiently eliminate normal cells no longer required in
      remodelling tissues, and abnormal cells exhibiting neoplastic phenotypes. Since
      injury is an important trigger to the development of vascular lesions, the
      balance of proliferation and apoptosis during the healing response, and
      aberrations of this process, may be important factors in lesion progression. The
      expression of genes that regulate this process, including c-myc and members of
      the bcl-2 and lce gene families, has been detected in the normal vasculature, and
      in atheromatous tissues. These observations suggest that the transfer of
      apoptosis-inducing genes into vascular lesions may be a feasible, non
      inflammatory strategy to eliminate the cellular components of restenotic and
      atherosclerotic plaques.

PMID- 9552512
TI  - Adenovirus-mediated arterial gene therapy for restenosis: problems and
      perspectives.
AB  - Restenosis remains the main limitation of interventional cardiology. Restenosis
      occurs when angioplasty-induced intimal hyperplasia as well as arterial
      remodelling result in flow-limiting renarrowing of the arterial lumen at the
      angioplasty site. Intimal hyperplasia is an important candidate for gene therapy
      since it is related to smooth muscle cell proliferation, which is an inviting
      target for molecular antiproliferative strategies. To date, adenoviral vectors
      are, by far, the most efficient vectors to perform in vivo arterial gene
      transfer. These vectors, as well as others, have been recently used to
      demonstrate that therapeutic genes encoding cytotoxic (herpes virus thymidine
      kinase) or cytostatic (hypophosphorylatable Rb, Gax, endothelial nitric oxide
      synthase) products successfully inhibit smooth muscle cell proliferation and
      related intimal hyperplasia. Despite substantial progress, major technical
      issues, including the toxicity of first-generation adenoviral vectors,
      inefficient transduction of atherosclerotic arteries, and the risk of extra
      arterial transfection remain to be addressed before gene therapy is applied to
      clinical restenosis.

PMID- 9552513
TI  - Gene inhibition and gene augmentation for the treatment of vascular proliferative
      disorders.
AB  - Gene therapy is emerging as a potential strategy for the treatment of
      vasculoproliferative diseases such as restenosis after angioplasty, vascular
      bypass graft occlusion and transplant coronary vasculopathy for which no known
      effective therapy exists. Our laboratory has demonstrated that vascular smooth
      muscle proliferation and lesion formation can be prevented by the blockade of
      genes regulating cell cycle progression. With this approach it was also shown
      that genetically engineered bioprostheses can be developed that are resistant to
      accelerated atherosclerosis and thus to graft failure. We have also reported that
      the direct in vivo transfer of a cDNA encoding endothelial nitric oxide synthase
      resulted in inhibition of neointimal lesion formation and improvement of vascular
      reactivity, demonstrating that therapeutic effects can also be achieved by the in
      vivo transfer of gene(s) whose product(s) exert a paracrine effect on the vessel
      wall.

PMID- 9552514
TI  - Methods of local gene delivery to vascular tissues.
AB  - The development of methods employing the introduction of new genetic material for
      therapeutic applications in the cardiovascular system is dependent not only on
      the evolution of molecular vectors, but also 'mechanical vectors' encompassing a
      variety of mechanisms and approaches for the delivery of vectors or vector
      modified cells to anatomical regions of interest. A significant challenge lies in
      the evolution of mechanical devices capable of highly efficient, localized and
      homogeneous delivery. Each of these three characteristics, though very desirable,
      remains generally elusive for several kinetic and physical reasons. Recently
      developed devices which render possible minimally-invasive peri- or epivascular
      delivery may provide advances in these aspects of delivery.

PMID- 9552515
TI  - Naked cDNA encoding secreted proteins for intra-arterial and intramuscular gene
      transfer.
AB  - Experience with intra-arterial and intramuscular gene transfer of VEGF
      illustrates in prototypical fashion how features of the gene, protein, and target
      tissue may all contribute to phenotypic modulation of the host despite the low
      transfection efficiency typical of naked plasmid DNA. These features include the
      fact that VEGF is naturally secreted, binds to cell-surface heparan sulfates, is
      generated by hypoxic endothelial cells, reduces apoptosis, and binds to high
      affinity receptors that are upregulated by hypoxia. Thus the success of gene
      therapy is not solely a function of vectors or transfection efficiency.

PMID- 9552516
TI  - Coronary stenting.

PMID- 9552517
TI  - Clinical trials on intracoronary stenting.
AB  - The stent is currently taking the lead in the treatment of obstructive coronary
      artery disease. The interest in this device is not only reflected by the relative
      number of patients referred for angioplasty and treated with a stent but also by
      the large number of clinical trials. These can be divided into trials assessing
      the safety and feasibility of the implantation of second generation or new
      stents, studies assessing novel treatment strategies and randomized clinical
      trials. With respect to the latter, they all compare stent implantation with
      balloon angioplasty. Of major importance will be the comparison of stent
      implantation with surgical revascularization of obstructive coronary artery
      disease. The increasing number of therapeutic options, however, confront the
      physician with the difficult choice and responsibility of selecting the most
      appropriate treatment. Therefore, systematic and objective evaluation of the
      available therapeutic approaches by means of appropriately designed trials is
      imperative. The purpose of this paper is to summarize and to put into perspective
      the various studies on intracoronary stenting. Distinction is made between
      observational studies testing a device or evaluating a new concept in
      intracoronary stenting and randomized clinical trials.

PMID- 9552518
TI  - An overview of US coronary stent trials.
AB  - Since the introduction of coronary stent procedures in the US there has been a
      determined effort to understand appropriate clinical applications better through
      the use of carefully designed prospective clinical trials. These studies fall
      into the general categories of efficacy studies, pharmacology, studies,
      intravascular ultrasound studies, adjuvant stent therapy studies, stent versus
      stent studies and new stent registries. Most of the pivotal clinical trials have
      been randomized controlled studies, but there have also been several carefully
      performed registry analyses which have provided useful insights. There are ample
      data to support the use of stents for abrupt and threatened closure syndrome.
      STRESS (the STent REStenosis Study) helped to establish the 'anti-restenosis'
      efficacy of elective Palmaz-Schatz coronary stent placement in native coronary
      arteries, although secondary complications (subacute stent thrombosis, bleeding
      and vascular events) were disturbing owing to excessive systemic anticoagulation
      regimens. Subsequent studies, often using intravascular ultrasound guidance, have
      clearly indicated that optimal stent implantation requiring post-stent high
      pressure dilatations combined with aggressive antiplatelet therapy (aspirin plus
      ticlopidine) provides the best early and late clinical outcomes. Many of these
      observations have now been extended to other lesion subsets including saphenous
      vein grafts. In the future, stent adjuvant therapies will be carefully evaluated,
      including pharmacological agents, intravascular irradiation, and pre-stent
      atheroablation. Finally, interstent comparisons of randomized clinical trials are
      ongoing and there are several new stent registries which will help to extend the
      frontiers of clinical applications and operator technique.

PMID- 9552519
TI  - Clinical and angiographic outcome of elective stent implantation in small
      coronary vessels: an analysis of the BENESTENT trial.
AB  - We examined the influence of vessel size using an intention-to-treat approach in
      259 patients who underwent stent implantation and in 257 patients who underwent
      balloon angioplasty alone in the BENESTENT trial. In the stented population,
      smaller vessel size was associated with a higher stent:vessel ratio, a greater
      relative gain and a greater subsequent loss index, and a higher risk of adverse
      cardiac events. In the balloon angioplasty population small vessel size conveyed
      an increased requirement for revascularization but did not increase the risk of
      procedural failure or myocardial infarction during follow-up. Logistic regression
      indicated that decreasing vessel size (as a continous variable) was associated
      with an increasing risk of a cardiac event for both the stent and balloon
      angioplasty populations.

PMID- 9552520
TI  - Cost effectiveness of stent implantation versus PTCA: the BENESTENT experience.
AB  - The aim of this paper is to assess the costs and effects of stent implantation
      versus percutaneous transluminal coronary angioplasty (PTCA). Data have been
      taken from both the BENESTENT-I and BENESTENT-II pilot study. Effects are
      expressed in terms of event-free survival and costs include those of the initial
      hospitalization and those during follow-up. The costs per additional event-free
      survivor after 7 months are estimated at Dfl 88,315, Dfl 28,127 and Dfl 6747
      using respectively the results from the BENSTENT-I study, the BENESTENT-II pilot
      study and phase IV of the BENESTENT-II pilot study. Significant decreases in
      complications and ischaemic events have made stent implantation not only the most
      favourable in terms of event-free survival but also in terms of cost
      effectiveness.

PMID- 9552521
TI  - Provisional stenting--stent-like balloon angioplasty: evidence to define the
      continuing role of balloon angioplasty for percutaneous coronary
      revascularization.
AB  - To clarify the current role of balloon angioplasty in interventional cardiology,
      in an era of increasing development of new devices, especially stents, we
      performed a retrospective comparative evaluation within the well-known BENESTENT
      trial. We defined a balloon angioplasty result of diameter stenosis less than 30%
      by quantitative angiography a 'stent-like' result and compared 6-month
      angiographic and 1-year clinical outcome with patients undergoing Palmaz-Schatz
      stent implantation. Patients having a so-defined 'stent-like' result had similar
      angiographic and clinical outcomes to patients receiving a stent. It is concluded
      that achievement of a postangioplasty diameter stenosis less than 30% may be
      considered clinically equivalent to the average result of Palmaz-Schatz stent
      implantation.

PMID- 9552522
TI  - 'Bail out' stenting: case closed.
AB  - Since the first description of percutaneous transluminal coronary angioplasty
      (PTCA), the number of patients who have undergone this procedure has rapidly
      increased. Two problems have plagued PTCA: acute vessel closure and restenosis.
      Acute vessel closure following PTCA increases the incidence of in-hospital death,
      myocardial infarction and coronary bypass grafting. The advent of intracoronary
      stenting for acute closure has had a profound impact on these complications.
      Complications following intracoronary stenting have declined with modification of
      anticoagulation post-stenting and an improved understanding of stent mechanics.
      Further refinement of these devices and continued improvement in our
      understanding of them should lead to further reduction of post-stent
      complications and improved patient outcomes.

PMID- 9552578
TI  - Changes in energy metabolism of calf muscle in patients with intermittent
      claudication assessed by 31P magnetic resonance spectroscopy: a phase II open
      study.
AB  - Energy status and metabolism in skeletal muscle of nine patients with peripheral
      arterial disease and suffering from intermittent claudication were evaluated
      using 31phosphorus magnetic resonance spectroscopy (MRS) before and after
      treatment for 3 months with propionyl-L-carnitine (PLC; 2 g/day p.o.). Maximum
      walking distance (MWD) was assessed on a standard treadmill (4 km/h, zero
      incline). For the group as a whole 31P MRS results did not change significantly
      with PLC. Although MWD increased by a mean of 36%, this change did not reach
      significance. However, when these variables were assessed with respect to the
      change in MWD, there were significant differences between those who increased MWD
      by > 30% (responders, R; n = 5) and those who did not (nonresponders, NR; n = 4).
      Compared with pretreatment values, during exercise the decrease in muscle pH in R
      relative to the decrease in phosphocreatine was less after PLC (p = 0.04). After
      exercise there was a significant inverse correlation between the changes in
      recovery half-time (t1/2) for phosphocreatine and in MWD (r = -0.91, p = 0.01).
      With PLC, Vmax increased in R (p = 0.04), but not in NR. For the patient group as
      a whole, the changes in Vmax and MWD correlated positively (r = 0.90, p = 0.01).
      This study helps to identify the changes in muscle metabolism that correlate with
      changes in exercise performance, and may accompany treatment with PLC.

PMID- 9552579
TI  - A novel therapy for lymphedema complicated by lymphorrhea.
AB  - Lymphorrhea is a rarely described complication of chronic lymphedema, in which
      the disrupted flow through diseased lymphatic channels gives rise to the external
      drainage of lymph, often heralded by the presence of an enlarging lymphocele.
      This report documents the applicability of the Reid sleeve, a novel, conservative
      form of therapy, in an unusually severe and protracted example of lymphorrhea.

PMID- 9552580
TI  - Vascular permeability/vascular endothelial growth factors: a potential role in
      the pathogenesis and treatment of vascular diseases.

PMID- 9552581
TI  - Positive and negative regulation of angiogenesis: from cell biology to the
      clinic.
AB  - Virtually every subspecialty in medicine in one way or another deals with
      angiogenesis-associated physiological or pathological processes and, without
      exception, every organ system in the body has many diseases in which angiogenesis
      is an important component. This in itself makes the study of angiogenesis
      mandatory, in both basic science and clinical settings. Yet the study of
      angiogenesis does not require this justification. As a biological process it is
      extraordinarily rich, touching on virtually every aspect of modern cell biology,
      making it almost impossible for molecular biologists, biochemists and
      morphologists to ignore. Considerable therapeutic benefit can now be obtained
      through positive or negative manipulation of the angiogenic process, and this is
      due in large part to the rapid transfer to the clinical setting of knowledge
      acquired through a cell biological approach.

PMID- 9552582
TI  - Atheromatous embolism.

PMID- 9552583
TI  - The diagnosis and clinical manifestations of activated protein C resistance: a
      case report and review of the literature.
AB  - Activated protein C resistance (APCR) is a recently discovered, medically
      important cause of venous thrombosis. More than 95% of cases are due to factor V
      Leiden (FVL), a mutated form of factor V that is resistant to degradation by
      activated protein C. The prevalence of this disorder, which is inherited in an
      autosomal dominant fashion, is approximately 5% among asymptomatic people of
      European heritage. In addition, 20 to 60% of patient cohorts with previous
      thrombosis demonstrate APCR, making it the most common known genetic cause of
      abnormal thrombophilia. Current laboratory techniques available for diagnosis
      include functional assays, such as the APC ratio, as well as DNA-based tests that
      detect the specific genetic anomaly responsible for FVL. A case report is
      presented, along with a review of the literature highlighting epidemiology,
      pathogenesis, clinical features and methods for laboratory diagnosis.

PMID- 9552584
TI  - Dermatologic findings associated with antiphospholipid antibody syndrome.

PMID- 9552585
TI  - The treatment of iliac artery atherosclerosis with angioplasty and intravascular
      stents.

PMID- 9552586
TI  - Images in vascular medicine. Giant cell arteritis of axillary artery.

PMID- 9552622
TI  - A clinical method to determine the effectiveness of dental handpiece
      sterilization.

PMID- 9552623
TI  - Beyond referrals: a smart Yellow Pages investment can bolster your bottom line.

PMID- 9552624
TI  - Peer review in the 90's.

PMID- 9552625
TI  - Treat patients with respect.

PMID- 9552626
TI  - Through an eyeglass darkly.

PMID- 9552627
TI  - The field of implantology--an overview.

PMID- 9552629
TI  - Hiring and keeping good people--a guide to office organization (Part 3--The
      compensation package).

PMID- 9552628
TI  - The effects of lisinopril and nifedipine on parotid function: two case reports.

PMID- 9552630
TI  - Using comprehensive examinations to build productive dental practices.

PMID- 9552631
TI  - Health care, medical care and dental care--a comparative analysis.

PMID- 9552632
TI  - Marketing the dental practice.
AB  - Marketing is a system. While it is key and the scope of this article to offer 40
      internal/customer service, external/community marketing strategies, this is your
      goal. The combination of programs consistently applied, analyzed and modified
      makes a difference. Start with your internal/customer service program. Once that
      is in place you can expand to external/community marketing programs. Creativity
      and persistence are how strong dental practices are built!

PMID- 9552633
TI  - Valuing a practice for a partnership.

PMID- 9552634
TI  - Redefining our understanding of misbehaving child patients.

PMID- 9552635
TI  - Isolation of the field more important than ever.

PMID- 9552637
TI  - HMO dentistry (capitation): how to profit and be ethical at the same time.

PMID- 9552636
TI  - Clinical pathology case conference. Verrucous carcinoma.

PMID- 9552638
TI  - Direct metallic amalgam alternative: a research update.
AB  - Discussions between two group leaders at the National Institute of Standards and
      Technology (NIST) led to the suggestion that a mercury-free, silver-based
      material could be used for dental direct-filling applications. This concept
      brought about a new approach that, nonetheless, is still based on powder
      technology such as amalgams. The resulting material also retains the tin and
      silver components of conventional amalgams. The condensation of a loose powder
      mixture into a cohesive solid relies, however, on cold-welding across atomically
      clean silver-silver interfaces after a mild acid treatment of the surfaces. The
      National Institute of Dental Research (NIDR) and American Dental Association
      Health Foundation (ADAHF) became involved in the research in 1992, and ADAHF
      scientists continue to collaborate with NIST metallurgists and electrochemists
      toward the further development of this promising new technology.

PMID- 9552650
TI  - Rubber dam isolation of cervical lesions. Part 1: Alternative techniques which
      avoid injury to the periodontium.
AB  - While it is arguable that the operative procedures depicted in this article could
      have been done equally well with alternative forms of isolation, it is
      indisputable that rubber dam provides for the most thorough 'isolation' in the
      comprehensive sense of the term. It allows for the finite control over peripheral
      variables such as access and controlled gingival retraction. This in turn permits
      meticulous execution of restorative procedures within the luxury of 'true four
      handed dentistry'. Most operative procedures are done within the limitations of
      single handed dentistry as the other 'three hands' are involved with retraction,
      fluid evacuation and access control. The rubber dam is indeed indispensable and
      with the increased awareness of infection control it is conceivable that rubber
      dam isolation will continue to be associated with quality patient care. Part 2 of
      this article will detail the application of the 'Modified Gingival Retractor' in
      the isolation of cervical lesions.

PMID- 9552651
TI  - Additional precautions to prevent transmission of Creutzfeldt-Jakob disease and
      other prion diseases.

PMID- 9552652
TI  - Posterior composite resin restorations: assuring restorative integrity.
AB  - Vancouver practitioner William Liebenberg, with whose work FDI World readers will
      be familiar, here describes the techniques be applies to the creation of direct
      composite resin restorations. Sharing a number of his solutions to attaining
      adhesive excellence with posterior, tooth coloured restorations, Dr. Liebenberg
      uses a case study to illustrate the quest for aesthetically pleasing anatomical
      form, minimal postoperative sensitivity, and a durable bond.

PMID- 9552653
TI  - Periodontology matters.

PMID- 9552654
TI  - The Cambodian dental bus.

PMID- 9552655
TI  - Rubber dam isolation of cervical lesions. Part 2: Application of the 'modified
      gingival retractor'.

PMID- 9552656
TI  - Atraumatic restorative treatment technique.

PMID- 9552657
TI  - Cleft lip and palate surgery in Cambodia.

PMID- 9552658
TI  - Universal precautions and pathways of infection.

PMID- 9552659
TI  - Sterilisation: Part 1. Instrument preparation.

PMID- 9552660
TI  - Working together in Peru--language needn't be a problem!
AB  - International, co-operative links between dental schools are an increasingly
      common occurrence, especially in relation to elective visits for under-graduates.
      However, in this feature for FDI World Norman Whitehouse and Gillian Jones from
      the Cardiff Dental School in Wales, UK, describe how they came to meet and assist
      Teresa Rios Caro in Peru, in rather different circumstances, and how language
      need not be a barrier when goodwill prevails.

PMID- 9552661
TI  - Sterilisation: Part 2. Heat and chemical sterilisation.

PMID- 9552662
TI  - The World Health Organisation's Oral Health Programme (ORH).
AB  - FDI and WHO have recently negotiated an agreement which will enable enhanced co
      operation in the future. In this article, written especially for FDI World, Dr.
      Pakhomov describes how oral health fits into the overall WHO programme. The
      article describes the way in which communicable and non-communicable diseases
      have an impact on the world's population and how WHO has rationalised its
      resources to cope with the consequent demands.

PMID- 9552663
TI  - FDI World Dental Federation. Position statement on tobacco.

PMID- 9552664
TI  - The collection of the dental school in Berlin--a creation of Friedrich Busch.

PMID- 9552665
TI  - What causes oral cancer?

PMID- 9552666
TI  - Working together as a team.

PMID- 9552667
TI  - The single incisor.

PMID- 9552668
TI  - 1994--the World Year of Oral Health.
AB  - The FDI has declared 1994 the World Year of Oral Health--the WHO's World Health
      Day, 7 April 1994, is dedicated to Oral Health. This makes 1994 a unique year,
      during which the dental profession and organised dentistry worldwide will focus
      on the promotion and further development of oral health and oral health care-
      throughout the year.

PMID- 9552669
TI  - Caries world-wide.

PMID- 9552670
TI  - Dentistry at the grassroots in Trinidad and Tobago.

PMID- 9552671
TI  - Gallium alloys in dentistry.

PMID- 9552672
TI  - The green journal of Victor R. Pointer.

PMID- 9552673
TI  - The aesthetic harmony of upper incisors.

PMID- 9552674
TI  - FDI World Dental Federation. Policy statement on dental amalgam. Approved by the
      FDI's General Assembly, 7 October 1994.

PMID- 9552675
TI  - Mahlon Loomis, DDS, inventor of wireless telegraphy.

PMID- 9552676
TI  - The diagnosis and treatment of precancerous lesions.
AB  - Leukoplakia is the most common premalignant lesion of the oral mucosa. The term
      should be used only for white lesions that cannot be characterised as any other
      definable lesion. The chance of malignant transformation can to some extent be
      predicted on the basis of the clinical appearance, the oral subsite, and the
      histopathological findings in the biopsy. The management of patients with oral
      leukoplakia is primarily directed towards elimination of possible causative
      factors. If the lesion persists, treatment is recommended in most cases. Of the
      various available treatment modalities no one is superior to the others. Both
      treated and untreated patients should be scheduled for long term follow-up,
      probably life long, with 6-12 month intervals in order to he able to detect
      possible recurrences in an early stage. Erythroplakia is less common than
      leukoplakia, but carries a considerably higher risk of malignant transformation.
      Therefore, erythroplakias should always be removed and subsequently, followed up.

PMID- 9552677
TI  - Self-responsibility comes first--a Swiss perspective.

PMID- 9552679
TI  - Tooth numbering systems.

PMID- 9552678
TI  - The future is now! Five steps for making it happen.
AB  - In today's market, dentists need to be open to using different approaches for
      increasing patient awareness of how dentistry can benefit them. The five key
      areas of practice management addressed here are just a few of the many ways to
      keep your practice healthy in our changing profession. Dentists who are committed
      to improving patient communication and accommodating the needs of their patients
      will be the ones for whom the future is bright.

PMID- 9552680
TI  - Swiss mission for dental prevention in Peru.

PMID- 9552681
TI  - Oral health in Oman.

PMID- 9552683
TI  - FDI World Dental Federation. Policy statement on the equivalency of dental
      diplomas.

PMID- 9552682
TI  - Operation smile Kenya 1994: oro-facial cleft surgery.

PMID- 9552684
TI  - Smile Alaska style.

PMID- 9552685
TI  - The International Milk Fluoridation Programme.

PMID- 9552686
TI  - Disinfection. Testing and validating sterilisation procedures and health and
      immunisation for clinicians.

PMID- 9552687
TI  - Challenges of dentistry in Africa.

PMID- 9552688
TI  - The amalgam debate worldwide: science versus emotion, plus environment.

PMID- 9552690
TI  - Volunteer dentists--an update.

PMID- 9552689
TI  - The poor dental health of children in Pakistan.

PMID- 9552691
TI  - Additional precautions for tuberculosis and a self assessment checklist.

PMID- 9552692
TI  - Oral cancer--a worldwide problem.

PMID- 9552693
TI  - The Netherlands into Africa, Malta into Albania and Spain into Central America-
      worldwide dental aid.

PMID- 9552694
TI  - How do we recognise and treat oral cancer and potentially malignant lesions?

PMID- 9552695
TI  - Tonga dental health programme.

PMID- 9552696
TI  - FDI Infection Control Checklist.

PMID- 9552697
TI  - Using technology to reduce the costs of dentistry.

PMID- 9552698
TI  - The amalgam story continues. Interview by Stephen Hancocks.

PMID- 9552699
TI  - Dentistry in Sri Lanka.

PMID- 9552700
TI  - Rebuilding dental health in The Lebanon.

PMID- 9552701
TI  - The miswak as an aid in oral hygiene.

PMID- 9552702
TI  - FDI World Dental Federation. World Health Organization. Consensus statement on
      dental amalgam.

PMID- 9552703
TI  - The atraumatic restorative treatment (ART) technique in the English-speaking
      Caribbean.

PMID- 9552704
TI  - Hygienic maintenance of dental handpieces and turbines.

PMID- 9552705
TI  - FDI World Dental Federation. Position statement on fluorides and dental caries.

PMID- 9552706
TI  - Leadership skills for the dentist.

PMID- 9552707
TI  - Mercy ships.

PMID- 9552708
TI  - Update on tooth numbering.

PMID- 9552709
TI  - A short (3-day) course of azithromycin tablets versus a 10-day course of
      amoxycillin-clavulanic acid (co-amoxiclav) in the treatment of adults with lower
      respiratory tract infections and effects on long-term outcome.
AB  - The efficacy and safety of a 3-day regimen of azithromycin prescribed in the new
      tablet form and of a 10-day regimen of amoxycillin clavulanic acid (co-amoxiclav,
      Augmentin) were compared in patients with acute lower respiratory tract
      infections. Of the 144 enrolled patients, 123 had a Type 1 acute exacerbation of
      chronic bronchitis (AECB), three patients had pneumonia, and 18 had purulent
      bronchitis. Treatment was successful, defined as cure or major improvement on day
      14, in 59/62 (95%) patients in the azithromycin treatment group compared with
      54/61 (90%) patients in the co-amoxiclav. At 30 days, the incidence of success
      was 77% (48/62) in the azithromycin treated group, compared with 66% (40/61) of
      co-amoxiclav-treated patients. At 60 days, incidences were 66% (41/62) and 59%
      (36/61), respectively. Several pathogens were isolated: Haemophilus influenzae in
      21 patients (minimum inhibitory concentration (MIC) range for azithromycin 0.12-4
      mg/l; co-amoxiclav 0.25-4 mg/l); Streptococcus pneumoniae in nine (MIC
      azithromycin < or = 0.06 > or = 256 mg/l; co-amoxiclav < or = 0.06-1 mg/l); and
      Moraxella catarrhalis in 11 (MIC azithromycin < or =0.06-2 mg/l; co-amoxiclav <
      or = 0.06-0.5 mg/l). Microbiological response rates were comparable. A
      significant correlation between clinical and microbiological cure was found (p =
      0.02, power 0.6). In 15 (10%) patients, positive serology for viruses or atypical
      pathogens was found. In the co-amoxiclav-treatment group, 24 patients had mild
      adverse events (12 diarrhoea), compared with 27 treated with azithromycin (p =
      0.47). It is concluded that a 3-day regimen of azithromycin prescribed as tablets
      is as clinically and microbiologically effective as a 10-day regimen of co
      amoxiclav in the treatment of acute lower respiratory tract infections. Moreover,
      since the percentage of viral infections was low and a significant correlation
      between microbiological and clinical cure was found, this study shows that
      clinical symptoms can be used to establish which patients with AECB (Type 1)
      should be treated with antimicrobial agents.

PMID- 9552710
TI  - A broad-spectrum antifungal from the marine sponge Hyrtios erecta.
AB  - Spongistatin 1, a macrocyclic lactone polyether from the marine sponge Hyrtios
      erecta, was fungicidal for a variety of opportunistic yeasts and filamentous
      fungi, including strains resistant to amphotericin B, ketoconazole and
      flucytosine. In broth macrodilution assays, MICs ranged from 0.195 to 12.5
      microg/ml, and minimum fungicidal concentrations ranged from 3.12 to 25
      microg/ml. Initial disk diffusion screens with six related macrocyclic lactone
      polyethers from H. erecta and Spirastrella spinispirulifera, revealed that these
      polyethers were also antifungal. The fungicidal activity of spongistatin 1 was
      confirmed in killing kinetics studies, where killing of Candida albicans and
      Cryptococcus neoformans occurred within 6 and 12 h, respectively. During the
      killing kinetics experiments, non-treated C. albicans maintained the yeast
      morphology. However, elongated forms resembling germ tubes were the predominant
      morphologic form in spongistatin 1-treated C. albicans cultures. The
      spongistatins show promise as potential antifungal agents and as probes to study
      fungal morphogenesis and nuclear division.

PMID- 9552711
TI  - Quality assessment of glycopeptide susceptibility tests: a European collaborative
      study. European Glycopeptide Resistance Group.
AB  - The ability of seventy clinical laboratories in nine European countries to detect
      glycopeptide resistance in Gram-positive bacteria was investigated. Results of
      routine tests were compared with those on the same strains by a reference method
      in national co-ordinating laboratories. In addition, control strains were tested
      by some of the participants. Errors in reporting susceptibility of Staphylococcus
      aureus to teicoplanin and vancomycin and coagulase-negative staphylococci to
      vancomycin were < 1%. With coagulase-negative staphylococci however, 44 (3.4%)
      teicoplanin susceptible isolates were reported intermediate and six (0.4%)
      resistant; 18 (58.1%) of 31 teicoplanin intermediate isolates were reported
      susceptible and five (16.1%) resistant; and six of nine teicoplanin resistant
      isolates were reported susceptible and two intermediate. All seven isolates of
      enterococci intermediate to vancomycin were reported susceptible. Distribution of
      a known vancomycin intermediate strain of E. gallinarum indicated problems with
      vancomycin susceptibility testing (44.4% reported susceptible, 32.7%
      intermediate, 32.1% resistant) and identification (only 34.1% correct) of this
      organism. Two of 28 teicoplanin resistant enterococci and three of 30 vancomycin
      resistant isolates were reported susceptible. Among other organisms, one
      resistant Lactobacillus sp. was reported susceptible to teicoplanin and
      vancomycin. In reporting teicoplanin susceptible organisms, there were fewer
      errors with comparative/Stokes methods than with most other methods and more
      errors with the ATB and Sceptor methods than most other methods. None of the
      methods used were reliable for testing teicoplanin intermediate and resistant
      coagulase-negative staphylococci or low-level vancomycin resistant enterococci.
      Alternative methods, such as breakpoint screening, should be considered for
      detecting glycopeptide resistance.

PMID- 9552712
TI  - ERIC-PCR typing profiles of Enterobacter cloacae are stable after development of
      advanced cephalosporin resistance.
AB  - Enterobacterial repetitive intergenic consensus (ERIC) sequence polymerase chain
      reaction genotype profiles of Enterobacter cloacae were prepared for paired
      isolates which were obtained before and after the high level expression of the
      chromosomal cephalosporinase. These profiles were homologous within strain pairs
      which suggests that the acquired resistance does not lead to major chromosomal
      alterations. ERIC genotypes are therefore reliable markers in epidemiological
      investigations where antibiogram modifications may arise as a consequence of
      antibiotic exposure and beta-lactamase over-production..

PMID- 9552713
TI  - The activity of rifabutin against Mycobacterium leprae in armadillos.
AB  - The activity of rifabutin (LM 427) against Mycobacterium leprae was evaluated in
      armadillos inoculated earlier with human-derived M. leprae. Rifabutin was
      administered daily at a dose of 6 mg/kg body weight/day. The effect of rifabutin
      on M. leprae harvested from armadillos was determined by measuring the
      intracellular levels of ATP (an indicator of metabolic activity) of M. leprae and
      also their ability to multiply in the mouse footpads and in vitro in DH medium.
      Within 2 weeks of initiating the treatment, ATP levels declined to 21% of the
      original (pre-treatment level) and these M. leprae failed to multiply in the
      footpads of mice as well as in the in vitro culture system. This suggests that
      rifabutin was able to kill all M. leprae within 2 weeks. After 8 weeks the
      treatment was terminated and results showed that M. leprae from the treated
      armadillos remained non-viable in the mouse footpad system as well as in the in
      vitro system, indicating bactericidal action of rifabutin. The results suggest
      that rifabutin can be a substitute for rifampin in the leprosy multi-drug therapy
      regimen.

PMID- 9552714
TI  - Antimicrobial resistance in gonococci isolated from patients and from commercial
      sex workers in Harare, Zimbabwe.
AB  - The objective is to compare antibiotic resistance amongst gonococci isolated from
      different patient groups in Harare, Zimbabwe. Antimicrobial susceptibilities of
      Neisseria. gonorrhoeae were determined by disc sensitivity tests. The MICs for
      penicillin, kanamycin, ceftriaxone, norfloxacin and ciprofloxacin were determined
      using E-test strips. There were 147 isolates from symptomatic men, 47 isolates
      from symptomatic women, 29 isolates from asymptomatic women and 41 isolates from
      female commercial sex workers. A total of 119 (45%) isolates were PPNG and 23
      (16%) non-PPNG isolates had a penicillin MIC > 0.64 mg/l. Over 90% of isolates
      were resistant to TMP/SMX and 16% were resistant to tetracycline. Resistance was
      uncommon against kanamycin (6%), erythromycin (2%) or ceftriaxone ( < 1%). For
      kanamycin, the MIC90 was 32 mg/l, for ceftriaxone the MIC90 was < 0.032 mg/l for
      non-PPNG and < 0.064 mg/l for PPNG. For norfloxacin and ciprofloxacin the MIC90
      was < 0.064 mg/l for both PPNG and non-PPNG. Isolates from the commercial sex
      workers showed a significantly increased prevalence of PPNG, of penicillin
      tolerant non-PPNG and of tetracycline resistance. Four of the 41 isolates from
      sex workers showed multiple resistance (to penicillin, TMP/SMX, tetracycline and
      kanamycin) compared to 1/223 isolates from other groups (OR = 24.0).
      Antimicrobial resistance is common amongst gonococci in Harare, especially with
      isolates from commercial sex workers. In order for STD treatment to be
      implemented as an effective strategy in HIV control, continued monitoring of
      resistance patterns is essential.

PMID- 9552715
TI  - Gastric diffusion of antibiotics used against Helicobacter pylori.
AB  - Only a few pharmacological studies have been carried out on men and guinea pigs
      to determine the gastric diffusion of antibiotics, which are active against
      Helicobacter pylori. The results of these studies have been analysed in
      considering the physicochemical nature, the mode of administration, the way of
      gastric diffusion (topic and/or systemic) and the pharmacological interactions.
      The correlation of these pharmacokinetic results with those obtained in clinical
      trials is difficult because of the heterogeneity of the pharmacological and
      pharmacodynamic data. The absence of a convenient and suitable animal or in vitro
      study model renders further standardized pharmacokinetic studies in infected man
      and at steady state necessary.

PMID- 9552716
TI  - Inhibition of Listeria monocytogenes and Salmonella enteriditis by combinations
      of plant oils and derivatives of benzoic acid: the development of synergistic
      antimicrobial combinations.
AB  - This study describes inhibitory properties of combinations of oil of fennel, oil
      of anise or oil of basil with either benzoic acid or methyl-paraben against
      Listeria monocytogenes and Salmonella enteriditis. Micro-organisms were cultured
      at 37 degrees C in broth and viable counts measured over a 48-h period. S.
      enteriditis was particularly sensitive to inhibition by a combination of oil of
      anise, fennel or basil with methyl-paraben where there was < 10 CFU/ml after 1 h.
      L. monocytogenes was less sensitive to inhibition by each combination however
      there was a significant reduction in growth of 4-8 log by combinations of all
      oils and methyl-paraben at 8, 24 and 48 h. Synergistic inhibition by one or more
      combinations was evident against each micro-organism.

PMID- 9552717
TI  - Antibiotic resistance in Escherichia coli isolated from blood and cerebrospinal
      fluid: a 6-year study of isolates from patients in England and Wales.
AB  - A study of the incidence of resistance to antimicrobial drugs in Escherichia coli
      from blood and CSF made in England and Wales in the 6-year period 1991 1996 has
      demonstrated a significant increase in the incidence of strains resistant to
      ampicillin and ciprofloxacin, two antibiotics used for first-line therapy of
      invasive disease. In particular, there has been a dramatic change in the
      occurrence of isolates with low level or high level resistance to ciprofloxacin;
      over 90% of isolates in the high level group were also resistant to at least four
      other antimicrobials. Physicians in England and Wales should be aware that there
      is now an increasing possibility of treatment failures when ciprofloxacin is used
      for the treatment of invasive E. coli infections.

PMID- 9552718
TI  - Pharmacokinetics of miconazole in serum and exudate of pelvic retroperitoneal
      space after radical hysterectomy and pelvic lymphadenectomy.
AB  - Due to the increased number of compromised hosts with fungal infections, doctors
      have recently started prescribing antifungal agents. In the field of gynecology,
      however, the choice of which drug to use has been difficult. The efficacies of
      these drugs depend on their antifungal spectra, potencies and concentrations in
      tissues. The present study was designed to investigate the pharmacokinetics of
      miconazole in the exudate of the retroperitoneal space that is formed after
      radical hysterectomy and pelvic lymphadenectomy. A total of 600 mg of miconazole
      was administered to the patients for exactly 60 min using an automatic drip
      infusion pump. The parameters of the formulas analyzed by the two-compartment
      model were determined using the least-squares method, and a simulation curve was
      made. The maximum drug concentration (Cmax) of miconazole in serum was 6.26 mg/l
      1 h after drip infusion commencement and the t1/2 in serum was 8.86 h. The value
      of the area under the time-serum concentration curve (AUC) in serum was 19.13
      mg/h per l. The Cmax of miconazole in the exudate of the retroperitoneal space
      was 0.13 mg/l 2.48 h after the drip infusion was started. The value of AUC in the
      exudate was 2.52 mg/h per l.

PMID- 9552751
TI  - EEMCO guidance for the assessment of skin colour.
AB  - GENERAL DESCRIPTION: Colour assessment of skin by visual inspection alone may be
      precise for a given individual although comparison between colours is only
      possible when they are viewed simultaneously. Subjective colour expression is
      also difficult to communicate with consistency. The limitations of visual
      observations may be overcome by colour-order systems and by instrumental
      measurements using either reflectance spectrophotometry or reflectance
      colorimetry following the CIE (Commission Internationale de l'Eclariage)
      recommendations. Image analysis using sensitive colour video cameras is another
      accurate method to record and compare skin colours. The current instrumental
      methods have proven both sensitive and reliable. Numerical colour communication
      expresses colours more precisely than words and allows exact analysis of skin
      pigmentation and skin colour changes. LEARNING OBJECTIVE: The reader will be
      introduced to the origins of skin colours and with basic principles of their
      measurements. Methods of colour reading are reviewed with particular insight into
      practical procedures, pitfalls and correct interpretation of data.

PMID- 9552752
TI  - Skin diseases associated with hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is a bloodborne agent transmitted by apparent and
      inapparent parenteral procedures representing a frequent cause of liver disease
      world-wide. Both acute and chronic HCV infection may affect the liver as well as
      various non-hepatic tissues. Numerous extrahepatic disorders have been recognised
      in association with HCV infection among which dermatological diseases occupy a
      central part. Cutaneous necrotising vasculitis, mixed cryoglobulinemia, porphyria
      cutanea tarda and lichen planus are the major skin diseases frequently associated
      with HCV infection, but other skin disorders, such as Adamantiadis-Behcet
      syndrome, erythema multiforme and nodosum, malacoplakia, urticaria and pruritus,
      may also be linked to hepatitis C. Further studies are necessary to establish or
      refute an aetiopathogenetic role of HCV in these conditions. Skin manifestations
      are also part of the clinical picture of other extrahepatic disorders associated
      with HCV infection, such as thyroid dysfunction and HCV-related thrombocytopenia.
      The response to interferon alpha (alpha-IFN) therapy in skin diseases is
      unpredictable with some patients ameliorating, others remaining stationary and
      others deteriorating.

PMID- 9552753
TI  - Duodenal ulcer patients exhibit a greater skin response to histamine.
AB  - BACKGROUND: Histamine is considered a major mediator in the process of gastric
      acid secretion. When acid peptic activity overpowers the mucosal defense
      mechanism, peptic ulceration may develop. Is the hyperreactivity of patients with
      duodenal ulcer to histamine also expressed in the skin? OBJECTIVE: The aim of the
      present study was to assess the reactivity of patients with duodenal ulcer to
      histamine as reflected in the skin, by comparing the erythema and the cutaneous
      blood flow response to histamine in duodenal ulcer patients and healthy controls.
      METHODS: Twenty volunteers participated in the study: 10 duodenal ulcer patients
      and 10 age and gender matched healthy controls. Histamine was topically
      administered to the back and to the volar side of the forearm, and the induced
      response was quantified by spectrophotometry and laser Doppler flowmetry (LDF).
      The extent of the response and time parameters were compared. RESULTS: The
      maximum response, as measured by LDF, was greater in the peptic ulcer patients (P
      < 0.05) compared to healthy controls. Aging was accompanied by decreased
      responsiveness in both groups. CONCLUSION: The results suggest that some peptic
      ulcer patients exhibit a greater cutaneous response to topical application of
      histamine than healthy controls. As the methods used are non-invasive, simple and
      rapid, they might be useful in preclinical ulcer diagnosis and detection of
      patients at risk.

PMID- 9552754
TI  - Use of recombinant pemphigus vulgaris antigen in development of ELISA and IB
      assays to detect pemphigus vulgaris autoantibodies.
AB  - AIM/OBJECTIVE: The objectives of this study are: (1) to measure the titers of
      pemphigus vulgaris (PV) autoantibody in the sera of patients with active disease,
      using three different assays: (a) Indirect immunofluorescence (IIF) using monkey
      esophagus as a substrate, (b) immunoblot (IB) and, (c) enzyme-linked
      immunosorbent assay (ELISA) using recombinant PV antigen (rPVA). (2) To compare
      the sensitivity of these three assays. BACKGROUND: The titer of PV autoantibodies
      and disease severity and extent do not always correlate. This could be due to the
      lack of consistency and specificity of the substrate. Different results are
      obtained using different substrates. A standard substrate with uniformly
      controlled source of antigen would be more useful and clinically beneficial.
      METHODS: In this study we studied 25 PV patients, six each with bullous
      pemphigoid (BP), ocular cicatricial pemphigoid (OCP), mucous membrane pemphigoid
      (MMP), and herpes gestationis (HG), and sera from 16 normal subjects. IIF was
      used to determine the PV autoantibody using monkey esophagus. IB assay was used
      according to standard protocol using normal human epidermis and rPVA as
      substrates. ELISA was performed using rPVA as antigens expressed in E. coli.
      RESULTS: Sera of all 25 PV patients showed binding to the rPVA, normal human sera
      and the sera from the six BP, six OCP, six MMP, and six HG patients did not show
      any binding. In addition, we used antisera from rabbits immunized with PVA
      peptides (Bos-1, Bos-6) which also showed binding to rPVA, whereas normal rabbit
      sera did not show any reactivity. ELISA and IB titers in all the patients were
      2.5 to 160 times higher than with the conventionally used IIF assay. The titers
      of the PV specific autoantibody measured using the rPVA did not show
      statistically significant differences between the ELISA and IB assays.
      CONCLUSIONS: IB and ELISA are superior to IIF in evaluating the antibody levels
      in PV patients. ELISA is more practical and is preferable to IB and is
      recommended for clinical use.

PMID- 9552755
TI  - Generalized pustular drug eruptions: confirmation by in vitro tests.
AB  - BACKGROUND: Generalized pustular eruptions are characterized by acute onset of
      aseptic pustules in febrile patients with leukocytosis after exposure to the
      offending drug. They have been regarded as uncommon manifestations of adverse
      drug reactions. Until now few confirmation studies have been carried out.
      OBJECTIVE: Our purpose was to describe a series of patients with generalized
      pustular drug eruption. The diagnosis and etiological role of drugs in these
      cases was confirmed by two in vitro tests, namely the macrophage migration
      inhibitory factor (MIF) and the mast cell degranulation (MCD) tests. METHODS: The
      clinical, pathological and laboratory findings in six patients with generalized
      pustular eruption were studied prospectively. The MIF and MCD tests were
      performed with the drugs taken by the patients. RESULTS: The dermatological
      manifestations included numerous pustules on large erythematous areas, papules
      and erythema multiforme-like lesions. The pustular eruption developed between 12
      h and 5 days after the administration of the provoking drug. The
      histopathological changes were characterized by subcorneal pustules, papillary
      edema and mixed cell inflammatory infiltrate. In two biopsies the infiltrate
      displayed numerous eosinophils. Laboratory investigations revealed leukocytosis
      with neutrophilia (4 of 6 patients) and eosinophilia and hyperimmunoglobulinemia
      E (2 of 6 patients). MCD tests with the suspected drugs (Ampicillin, Cefazolin,
      Tetracycline, Griseofulvin, Enalapril Maleate) were positive in all patients.
      Positive MIF results were seen in five of the six patients. Withdrawal of the
      drug led to fast recovery. CONCLUSION: The diagnosis of pustular drug eruptions
      depends on circumstantial evidence, some characteristic clinicopathological
      findings and exclusion of alternative diagnoses of other disseminated pustular
      eruptions. In vitro tests, namely MIF and MCD tests, are a useful diagnostic aid
      in the identification of the offending drugs.

PMID- 9552756
TI  - Low-dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant
      recipients.
AB  - BACKGROUND: Renal transplant recipients have an increased incidence of skin
      cancers, which may be multiple and aggressive. OBJECTIVES: The purpose of this
      study was to examine the chemoprophylactic effects of low-dose etretinate (0.3
      mg/kg/day) on skin cancer development in renal transplant recipients and to
      monitor retinoid toxic effects at this dose. METHODS: All skin lesions were
      counted and photographed prior to therapy with etretinate. Patients were assessed
      at monthly intervals for new skin lesions and for retinoid toxicity. RESULTS:
      Eleven renal transplant recipients participated. There was a significant
      reduction in the number of skin cancers which occurred during etretinate therapy
      compared with pre-treatment for 3 and 6 months of treatment, and a trend towards
      fewer skin cancers in the 12 and 18 month treatment periods. Side-effects were
      well-tolerated and no significant biochemical effects were observed. CONCLUSION:
      Low dose etretinate is safe, well-tolerated and partially effective in
      chemoprophylaxis of skin cancer in renal transplant recipients.

PMID- 9552757
TI  - Classic Kaposi's sarcoma in two young heterosexual men.
AB  - Classic Kaposi's sarcoma is primarily a skin disease of the lower extremities
      affecting predominantly elderly men of Mediterranean origin. We report classic
      Kaposi's sarcoma first presenting in the third decade in two heterosexual, HIV
      negative, males of Greek origin from Albania. Ten years after onset, the disease
      became aggressive with unusual clinical features that included exophytic tumors,
      extensive lesions on the hands as well as the legs, and prominent leg edema. One
      of the patients also presented lesions on the face, trunk and palate, and bubonic
      lymphadenopathy. In both cases, CD4 counts were normal and HLA-DR5 was positive.
      Treatment included radiation therapy, subcutaneous interferon (alpha-2b) and
      combined chemotherapy (ABV). At follow up 1 and 2 years later, both patients
      remain in partial remission with significant improvement in clinical disease, on
      maintenance interferon.

PMID- 9552758
TI  - An unusual case of primary systemic amyloidosis.
AB  - Here we report an unusual case of primary systemic amyloidosis. The cutaneous
      lesions were polymorphic and included involvement of both external auditory
      canals. The visceral involvement was covert. Mapping of amyloid deposits was
      performed using scintigraphy with technetium-99m (V) dimercaptosuccinic acid
      ([99mTc (V)] DMSA). Therapy with melphalan, prednisone and colchicine resulted in
      considerable improvement.

PMID- 9552759
TI  - Cutaneous infection due to acremonium.
AB  - We report an immunocompromised patient who developed a cutaneous infection caused
      by acremonium which is a rare opportunistic fungi. With the increasing number of
      immunocompromised patients opportunistic fungal infection can cause serious
      diseases and early recognition is mandatory.

PMID- 9552760
TI  - Subcutaneous T-cell lymphoma: report of two cases.
AB  - We have seen two patients, a 24-year-old man and a 15-year-old girl, with
      subcutaneous nodules and fever. The histopathological findings in both cases
      showed a lobular, histiocytic panniculitis with 'bean bag' cells and lymphoid
      cells identified as immature T-cells. This picture was consistent with
      subcutaneous T-cell lymphoma associated with cytophagic histiocytic panniculitis.
      The girl died after 5 months of disease with florid hemophagocytic syndrome; the
      man was subjected to a course of treatment (CHOP;
      cyclophosphamide/doxorubicin/vincristine/prednisone) and after 6 months
      observation his symptoms of nodules and fever disappeared.

PMID- 9552761
TI  - Juvenile acute cutaneous leishmaniasis: the first case report from north
      Scandinavia.
AB  - A case of juvenile acute cutaneous leishmaniasis is reported. Treatment with
      freezing with CO2 snow was beneficial in healing of cutaneous lesions and no
      relapses have occurred.

PMID- 9552762
TI  - Linear IgA bullous dermatosis induced by piroxicam.
AB  - Linear IgA bullous dermatosis (LABD) is an acquired, autoimmune, heterogeneous
      subepidermal blistering disorder usually idiopathic in nature, but in recent
      years a variety of drugs have been reported to induce this disorder. We describe
      the first reported patient who developed LABD after ingestion of the non
      steroidal anti-inflammatory agent (NSAID) piroxicam.

PMID- 9552763
TI  - Hypomelanosis of Ito: a case report with clinical and ultrastructural data.
AB  - Hypomelanosis of Ito (HI) is an uncommon skin disorder characterized by the
      presence of hypochromic areas associated with visceral abnormalities, the most
      common being neurological, muscular, skeletal and ocular. The authors describe a
      typical case of hypomelanosis of Ito in a 7-year-old child. The patient was
      obese, suffered from scoliosis, flat feet and had a bilateral genu valgus. No
      neurological, ophthalmological or dental malformations were noted. An electron
      microscopic study of a hypomelanotic area showed decreased functional activity in
      the melanocytes, which contained only a few rudimentary cytoplasmatic projections
      and poorly developed organelles. In addition, there was a reduction in the number
      of mature melanosomes.

PMID- 9552764
TI  - African histoplasmosis: therapeutic efficacy of itraconazole.
AB  - A patient with African form of histoplasmosis was treated for 7 years with
      ketoconazole, with no response; after a 9-month daily treatment with 100 mg of
      itraconazole the patient was successfully cured. No evidence of relapse was
      observed during the 3-year follow-up period.

PMID- 9552765
TI  - Leukocytoclastic vasculitis induced by low-dose methotrexate: in vitro evidence
      for an immunologic mechanism.
AB  - The rare occurrence of methotrexate (MTX)-induced vasculitis has been associated
      mainly with high or intermediate MTX doses. We report herein a case of cutaneous
      leukocytoclastic vasculitis (LCV) following treatment with low-dose oral MTX (7.5
      mg/week) for rheumatoid arthritis. The histological findings of a cutaneous
      lesion were consistent with drug-induced vasculitis. The clinical and
      histological findings, including the temporal relationship between MTX intake and
      the onset of vasculitis, and the results of withdrawal and rechallenge tests,
      suggest a causal relationship, and indicate a drug-induced LCV due to MTX. The
      role of MTX in the induction of the vasculitis was further supported by a
      positive mast cell degranulation (MCD) test.

PMID- 9552766
TI  - Lyme borreliosis in the Emilia-Romagna region (Italy): identification of the
      etiological agent.

PMID- 9552767
TI  - Irritant contact dermatitis due to Dieffenbachia s.p.p.

PMID- 9552768
TI  - Randomised double blind controlled trial of 2% ketoconazole cream versus 0.05%
      clobetasol 17-butyrate cream in seborrhoeic dermatitis.

PMID- 9552769
TI  - Pemphigus vulgaris exhibiting Koebner phenomenon.

PMID- 9552771
TI  - The American Society of Regional Anesthesia: a founding partner of the American
      Board of Anesthesiology.

PMID- 9552770
TI  - Every problem is an opportunity, or one person's poison is another person's
      remedy.

PMID- 9552772
TI  - 2-Chloroprocaine and bupivacaine are unreliable indicators of intravascular
      injection in the premedicated patient.
AB  - BACKGROUND AND OBJECTIVES: Epinephrine-containing test doses for detection of
      intravascular injection during epidural anesthesia may be unreliable or hazardous
      in beta-blocked, elderly, or pregnant patients. Subtoxic injections of lidocaine
      have been used as an alternative marker of intravascular injection in
      unpremedicated patients. We studied two groups of premedicated patients and
      unpremedicated subjects to evaluate the reliability of the local anesthetics
      bupivacaine (B) and 2-chloroprocaine (2-CP) as test dose injections. METHODS:
      Thirty ASA I and II subjects received blinded randomized injections of 2-CP, B,
      or normal saline via a peripheral vein. RESULTS: In group I, 10 healthy
      unpremedicated volunteers universally recognized injection of 90 mg 2-CP or 25 mg
      B, but did not reliably detect the injection of 60 mg 2-CP. In group II, 20
      patients premedicated with 1 microg/kg fentanyl and 30 microg/kg midazolam could
      not reliably detect similar injections. Sixteen responded to the injection of 90
      mg 2-CP, while 13 detected the 25 mg B test dose. A blinded observer rated only
      12 of the subjective reports as conclusive of detection of intravascular
      injection after each drug. There were no false-positive reports in any group.
      CONCLUSIONS: While 90 mg 2-CP or 25 mg B may be reliable alternatives to
      epinephrine test doses in unpremedicated subjects, they are unreliable indicators
      of intravascular injection in the premedicated patient.

PMID- 9552773
TI  - Epidural pressures and spread of 2% lidocaine in the epidural space: influence of
      volume and speed of injection of the local anesthetic solution.
AB  - BACKGROUND AND OBJECTIVES: The impact of epidural pressures on the spread of
      epidural block is controversial. This study examined the effect of volume and
      speed of injection of local anesthetics on epidural pressures and the spread of
      anesthesia. METHODS: Twenty women undergoing epidural anesthesia received a test
      dose of 3 mL of 2% lidocaine with epinephrine 1:200,000 over 6 seconds and
      subsequently the main dose of 15 mL of the solution over 30 seconds (group I) or
      3 minutes (group II). Variables studied included epidural pressures and the
      extent and duration of thermal and sensory block. RESULTS: Peak epidural pressure
      following the main dose was significantly higher in group I as compared to group
      II. All other epidural pressures and the extent and duration of sensory and
      thermal block were similar in both groups. The peak epidural pressure in group II
      and the pressures obtained at 3 minutes after the main dose in both groups were
      inversely correlated with the extent of the thermal block and directly correlated
      with its regression time. CONCLUSIONS: The peak epidural pressures correlated
      with the speed of injection of the lidocaine solution and not with its volume,
      whereas the remaining epidural pressures correlated with its volume and not with
      the speed of injection. The extent and duration of the thermal block exhibited a
      more consistent correlation (inverse and direct, respectively) with the epidural
      pressures than those of the sensory block.

PMID- 9552774
TI  - Time course of the effects of cervical epidural anesthesia on pulmonary function.
AB  - BACKGROUND AND OBJECTIVES: During cervical epidural anesthesia the C4, C5, and
      sometimes C3 nerve roots are anesthetized. One might therefore expect pulmonary
      compromise due to the block of the phrenic nerve if anesthesia extends to C3.
      This study was conducted to measure the effects of cervical epidural anesthesia
      using 2% lidocaine on pulmonary function, with specific attention given to the
      time course of pulmonary changes in relation to spread of analgesia. METHODS:
      Fifteen adult patients without preexisting lung disease undergoing carotid
      endarterectomy, breast surgery, or cervical epidural steroid injection were
      enrolled. Cervical epidural anesthesia was performed at the C7-T1 interspace
      using 300 mg lidocaine with epinephrine. Pulmonary function, including forced
      expiratory volume in one second (FEV1), forced vital capacity (FVC), maximum
      inspiratory pressure (MIP), and SpO2 while breathing room air were measured prior
      to and 5, 10, 20, and 40 minutes after lidocaine injection. RESULTS: Analgesia to
      pinprick reached median dermatomes of C3 to T8 (range: C2-T12) by 20 minutes
      after lidocaine injection. FEV1 and FVC decreased approximately 12-16% between 20
      and 40 minutes after injection. Maximum inspiratory pressure and SpO2 did not
      significantly change. CONCLUSIONS: Cervical epidural anesthesia using 300 mg
      lidocaine results in measurable reduction in bedside pulmonary functions
      concomitant with the spread of analgesia to the C3 dermatome. These changes were
      complete 20 minutes after lidocaine injection. In patients without preexisting
      lung disease, these changes were not clinically significant, except in one
      patient. We conclude that motor block of the phrenic nerve is incomplete under
      the conditions of this study.

PMID- 9552775
TI  - High thoracic epidural block relieves acute herpetic pain involving the
      trigeminal and cervical regions: comparison with effects of stellate ganglion
      block.
AB  - BACKGROUND AND OBJECTIVES: Stellate ganglion block can promptly relieve acute
      herpetic pain (AHP) involving the trigeminal and cervical regions. However,
      repeated blocks are needed to maintain pain relief in most patients with severe
      AHP. Because continuous epidural block is easily performed using an indwelling
      catheter, we compared the effect of high thoracic epidural block with that of
      stellate ganglion block to relieve moderate-to-severe AHP involving these
      regions. METHODS: Six patients received stellate ganglion blocks and seven
      patients received high thoracic epidural blocks. Six milliliters 1% of
      mepivacaine was given to each patient. Acute herpetic pain was evaluated before
      and up to 60 minutes after the blocks, using a visual analog scale (VAS) of pain.
      RESULTS: There was no significant difference in VAS pain scores before the blocks
      between the groups, but there were significant (P < .05) decreases in VAS pain
      scores for both groups between 10 and 60 minutes after the blocks. There were no
      significant differences in VAS pain scores between the groups after the blocks.
      CONCLUSIONS: High thoracic epidural block was as effective as stellate ganglion
      block in relieving moderate-to-severe AHP involving the trigeminal and cervical
      regions.

PMID- 9552776
TI  - Sphenopalatine ganglion block for the treatment of myofascial pain of the head,
      neck, and shoulders.
AB  - BACKGROUND AND OBJECTIVES: This study examined the effectiveness of
      sphenopalatine ganglion block (SPGB) for myofascial pain syndrome of the head,
      neck, and shoulders using a double-blind, placebo-controlled, crossover study
      design with comparison to an internal standard consisting of trigger point
      injections (TPI). METHODS: Patients (n = 23) were randomly assigned to receive
      either: (1) SPGB with 4% lidocaine, then TPI with 1% lidocaine, and finally SPGB
      with saline placebo or (2) SPGB with saline placebo, then TPI with 1% lidocaine,
      and finally SPGB with 4% lidocaine. Each respective treatment within each
      protocol was given sequentially at 1-week intervals for both groups. Prior to the
      first treatment, all patients assessed their average intensity of pain and pain
      at that particular moment using a visual analog pain scale. Pain intensity and
      pain relief were reassessed 30 minutes after each treatment and at 6 hours, 24
      hours and 1 week using visual analog pain and pain relief scales. Pain intensity
      and pain relief data were transformed into natural logarithm units, and the
      statistical significance of SPGB with 4% lidocaine versus SPGB with placebo, SPGB
      with 4% lidocaine versus TPI, and TPI versus SPGB with placebo were tested by
      mixed-model analysis of variance. The magnitude of the differences in pain
      intensity and pain relief ratings were also compared via computation of 95%
      confidence intervals. RESULTS: The analgesic effect of SPGB with 4% lidocaine was
      no better than placebo. Mixed-model analysis of variance revealed improved
      analgesia with administration of TPIs as compared to SPGB with 4% lidocaine and
      placebo over the entire week of observations (pain relief scores). CONCLUSIONS:
      This study suggests that SPGB with 4% lidocaine is no more efficacious than
      placebo and less efficacious than administration of standard trigger point
      injections in the treatment of myofascial pain of the head, neck, and shoulders.

PMID- 9552777
TI  - Celiac plexus block: a reappraisal.
AB  - BACKGROUND AND OBJECTIVES: The neurolytic celiac plexus block is an established,
      well-developed procedure and the most widely applicable of all the neurolytic
      pain blocks. It optimizes palliative treatment for cancer of the upper abdominal
      viscera. Several techniques have been proposed in an attempt to increase success
      rates, reduce morbidity, and enhance technical accuracy. However, the assessment
      of the results and effectiveness of the block have been controversial. METHODS: A
      survey was made of pertinent English language literature on the anatomic and
      technical problems, indications, advantages, complications, and outcomes related
      to the neurolytic celiac plexus block as well as the neurolytic solutions and
      radiologic guidance used. RESULTS: The successful relief of the pain of
      pancreatic cancer and other abdominal malignancies can be expected in 85% and 73%
      of patients, respectively. Following the block, many patients can be weaned from
      opioids or at least have their dose reduced. The half-life of the celiac plexus
      block seems to be more than 4 weeks. The probability of patients remaining
      completely pain-free diminishes with increases survival time. The technique
      selected should be appropriate to the available and the extent of malignancy,
      since the analgesic results seem to be independent of the principal techniques
      used. Serious complications are extremely rare. However, critical analysis
      revealed major deficiencies in all of the reports reviewed. CONCLUSION:
      Neurolytic celiac plexus block alone is capable of providing complete pain relief
      until death in a few cases and, therefore, should be considered as an adjuvant
      treatment in the analgesic strategy. Combination palliative therapy is necessary
      in most cases. Failure of the block may be attributed to tumor metastasizing
      beyond the nerves that conduct pain via the celiac plexus and the component
      nerves that form it. Concomitant pain of somatic origin (frequently observed in
      upper gastrointestinal cancer because of significant peritoneal involvement)
      requires other therapeutic measures.

PMID- 9552778
TI  - Enhancement of analgesic effect of intrathecal neostigmine and clonidine on
      bupivacaine spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Intrathecal administration of neostigmine has been
      shown to produce analgesia in both animals and humans. The concurrent
      administration of intrathecal neostigmine and clonidine has been reported to
      produce no neurotoxicity in sheep. The purpose of the present study was to
      evaluate the efficacy and safety of the combining intrathecal neostigmine and
      clonidine for the relief of pain in patients after cesarean delivery. METHODS:
      After giving their consents, 80 parturients who were scheduled for cesarean
      delivery during spinal anesthesia were enrolled by a double-blind randomized
      design into four groups: bupivacaine group (n = 20) received intrathecal (i.t.)
      10 mg bupivacaine; bupivacaine + neostigmine group (n = 19) received i.t. 10 mg
      bupivacaine + 50 microg neostigmine; bupivacaine + clonidine group (n = 20)
      received i.t. 10 mg bupivacaine + 150 microg clonidine; and bupivacaine + both (n
      = 21) received i.t. 10 mg bupivacaine + 50 microg neostigmine + 150 microg
      clonidine. The maximum spread of anesthesia, duration of analgesia and motor
      block, vital signs, and incidence of adverse effects were recorded for 14 hours
      postinjection. Fifty milligrams intramuscular meperidine was given as a rescue
      analgesic whenever patient's pain score was greater than 5/10 by the visual
      analog scale. RESULTS: The demographic data were similar for all four groups.
      Bupivacaine + both group had a significantly higher maximum spread of anesthesia
      of 23.3 +/- 2.9 segments than bupivacaine group of 20.5 +/- 2.9 segment.
      Bupivacaine + both group showed a later onset of postsurgical pain of 6.5 +/- 1.5
      hours as compared to bupivacaine group of 1.3 +/- 0.6 hours. The pain score in
      bupivacaine + both group was significantly lower than that of bupivacaine group
      during the first 10 hours. The 24-hour meperidine consumption also was lower in
      bupivacaine + both group than that of bupivacaine group. However, motor block was
      significantly prolonged from 3.5 +/- 1.1 hours in bupivacaine group to 7.1 +/-
      1.6 hours in bupivacaine + both group. In addition, other side effects such as
      nausea and vomiting and dizziness were significantly increased in bupivacaine +
      both group. CONCLUSION: Our study showed that the combination of 150 microg i.t.
      clonidine and 50 microg neostigmine provided longer postsurgical analgesia than
      with either drug used alone. However, this combination also produced
      significantly more adverse effects of prolonged motor block and nausea and
      vomiting. A further study combining the two study drugs but using a lower dose of
      i.t. neostigmine (e.g., 25 microg) is recommended.

PMID- 9552779
TI  - Incisional morphine has no analgesic effect on postoperative pain following
      inguinal herniotomy.
AB  - BACKGROUND AND OBJECTIVES: Opioids induce antinociceptive effects after
      peripheral administration in experimental and clinical studies. The results of
      the clinical studies are conflicting. The objective of this study was to examine
      a possible analgesic effect of incisionally administered morphine on
      postoperative pain in patients undergoing inguinal herniotomy during general
      anesthesia. METHODS: Forty-six consecutive outpatients were included in a double
      blind, randomized, placebo-controlled study. At conclusion of herniotomy 5 mg
      morphine was injected incisionally in 11 patients, intravenously in 10, and
      subcutaneously in 13. The placebo group of 12 had saline injected in the
      incision. Postoperative pain at rest and during mobilization was assessed with a
      visual analog scale. Assessments were made immediately before and after
      herniotomy, at 2, 4, and 6 hours after surgery, and on the second and seventh
      postoperative day. Postoperative morphine and acetaminophen consumptions were
      recorded within the same period. RESULTS: There were no significant differences
      in visual analog scores between the groups at any time during the study. Overall
      differences in postoperative acetaminophen and morphine consumptions were
      insignificant. CONCLUSIONS: The analgesic effect of a single 5 mg dose of
      morphine injected in a herniotomy wound is not superior to saline or to morphine
      given subcutaneously or intravenously.

PMID- 9552780
TI  - Comparison of remifentanil and propofol infusions for sedation during regional
      anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Patients treated with regional anesthesia often
      require concomitant medication for comfort and sedation. Propofol is widely used
      for this purpose. Remifentanil, a new ultra-short-acting opioid, exhibits at low
      doses distinct sedative properties that may be useful for supplementation of
      regional anesthesia. This study compared the effectiveness of remifentanil and
      propofol infusions for providing sedation during regional block placement and
      surgery. METHODS: In an open, prospective trial, 28 patients were randomly
      allocated to receive continuous infusions of remifentanil (6 microg/kg/h) or
      propofol (3 mg/kg/h) for sedation during spinal or axillary regional anesthesia.
      Infusion rates were titrated to maintain a sedation level > or = 2 as assessed
      with the Observer's Assessment of Alertness Scale. Vital signs were measured
      continuously, during and for 2 hours after ending study drug infusion. RESULTS:
      Similar scores for comfort and sedation were obtained in both groups during
      placement of the regional block and during surgery. Degree of sedation correlated
      with drug infusion rate of remifentanil (P < .002) but not for propofol.
      Respiratory rate decreased in the remifentanil group in absence of surgery (P <
      .05). Mean arterial pressure and heart rate were 20% lower in the propofol group
      (P < .05). Return to alertness occurred after 10 +/- 6 minutes in the
      remifentanil group and after 16 +/- 15 minutes in the propofol group. Similar
      incidences of hypotension, bradycardia, and nausea and vomiting were found in
      both groups, but intraoperative respiratory depression and nausea were more
      prominent in the remifentanil group. CONCLUSIONS: When titrated to the same
      sedation level, remifentanil provided a smoother hemodynamic profile than
      propofol during regional anesthesia. The frequent occurrence of remifentanil
      induced respiratory depression requires cautious administration of this agent.
      The incidence of adverse reactions seen with both agents during and after their
      administration makes the management of such sedative infusion techniques
      difficult.

PMID- 9552781
TI  - Bupivacaine-induced convulsion is suppressed by MK-801.
AB  - BACKGROUND AND OBJECTIVES: Not only the facilitation of inhibitory synapses but
      also the suppression of excitatory synapses may be effective in treating
      convulsion induced by local anesthetics. The effects of MK-801, a N-methyl-D
      aspartate (NMDA) receptor antagonist, on bupivacaine-induced convulsion and
      hemodynamic changes were studied. METHODS: Cortex and hippocampal (A4; L5.5; H8)
      electroencephalogram (EEG), heart rate, and mean arterial pressure were measured
      in 21 cats anesthetized with urethane. Blood samples were obtained when cats
      demonstrated arrhythmias, convulsed, and became hypotensive. In the control group
      (n = 7), bupivacaine was continuously infused until a hypotensive state of 40
      mm/Hg was reached. In the MK-801 pretreated group (n = 7), MK-801 (0.5 mg/kg) was
      injected intravenously 15 minutes before the bupivacaine injection. In the MK-801
      treatment group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously at the
      appearance of convulsive EEG after the bupivacaine injection. RESULTS:
      Bupivacaine produced convulsion in the control group (17.1 +/- 2.4 microg/mL),
      but not in the MK-801 pretreated group. In the treatment group, convulsive EEG
      was suppressed gradually after injection of MK-801. The mean plasma bupivacaine
      concentrations (microg/mL) reaching arrhythmia and hypotension were 9.5 +/- 2.9
      and 23.0 +/- 3.0, respectively, in the control group; 10.9 +/- 3.5 and 22.5 +/-
      4.9, respectively, in the MK-801 pretreated group; and 7.5 +/- 1.6 and 21.0 +/-
      3.0, respectively, in the MK-801 treatment groups. The mean arterial pressure and
      heart rate did not differ among the three groups. CONCLUSIONS: These results
      demonstrated that one mechanism of bupivacaine-induced convulsion is the
      excitatory neurotransmitter system in central nervous system and that MK-801 is
      effective in suppressing the convulsion without any effects on hemodynamics.

PMID- 9552782
TI  - Defining the cross-sectional anatomy important to interscalene brachial plexus
      block with magnetic resonance imaging.
AB  - BACKGROUND AND OBJECTIVES: Interscalene brachial plexus block is a useful
      technique to provide anesthesia and analgesia for the shoulder and proximal upper
      extremity. The initial needle direction at the interscalene groove has been
      described as being "perpendicular to the skin in every plane" (1). A cross
      sectional (axial) approach may offer a more easily conceptualized directed needle
      placement. The purpose of this study is to define the cross-sectional anatomy and
      idealized needle angles important to interscalene brachial plexus block. METHODS:
      Following IRB approval, 50 patients were studied. Cross-sectional volume coil T1
      weighted magnetic resonance images (MRI) were obtained from 50 patients
      undergoing cervical region imaging for other reasons. At the interscalene groove,
      a simulated needle path to contact the ventral rami or trunks of the brachial
      plexus was approximated at the level of C6 or C6-C7 interspace. The angle of this
      needle path intersecting the sagittal plane was recorded for each patient.
      RESULTS: The mean angle of the simulated needle path relative to sagittal plane
      was determined to be 61.1 +/- 6.1 degrees (range, 50-78 degrees). In 13 of 50
      (26%) MRI scans, the cervical nerve roots were not visualized at the level of C6
      and were measured at the C6-C7 level. CONCLUSIONS: These findings suggest initial
      needle placement at the interscalene groove should be angled less perpendicularly
      relative to the sagittal plane than is often observed. A cross-sectional approach
      enables more practical visualization of initial needle placement. A more accurate
      initial needle placement may minimize the number of needle passes necessary to
      contact the nerve roots, thereby more efficiently obtaining a successful block.

PMID- 9552783
TI  - Intrathecal addition of morphine to bupivacaine is not the cause of postoperative
      nausea and vomiting.
AB  - BACKGROUND AND OBJECTIVES: Postoperative nausea and vomiting after anesthesia is
      an distressing side effect. This study was undertaken to determine to what extent
      spinal opioids contribute to postoperative nausea and vomiting (PONV) and
      secondly to how effectively metoclopramide can reduce the incidence of PONV after
      intrathecal administration of morphine. METHODS: Patients were allocated to three
      groups all undergoing major joint surgery of the lower limb. In group 1 (n =
      200), intrathecal anesthesia was assessed by administration of 20 mg bupivacaine
      and 0.2 mg morphine. In Group 2 (n = 100) intrathecal anesthesia was assessed in
      the same way and in addition, 20 mg metoclopramide intramuscular during
      maintenance of anesthesia and a second dose of 20 mg metoclopramide was
      administered intramuscular after arrival at the recovery room. Finally, in group
      3 (n = 100), intrathecal anesthesia was assessed after administration of 20 mg
      bupivacaine. RESULTS: The maximum PONV percentages were 41.1%, 32.7%, and 37% in
      groups 1, 2, and 3, respectively. The consumption of antiemetics was similar in
      all groups. The number of patients who needed one or more additional antiemetics
      during the first 24 hours after surgery was 112 (56.6%), 57 (58%), and 60 (60%)
      in groups 1, 2, and 3, respectively. CONCLUSIONS: Administration of
      metoclopramide did not reduce the overall incidence of PONV. Our study shows no
      relationship between the use of intrathecal morphine and the incidence of PONV
      during the first 24 hours postoperative.

PMID- 9552784
TI  - The effects and side effects of interscalene brachial plexus block by posterior
      approach.
AB  - BACKGROUND AND OBJECTIVES: To investigate the use of interscalene block by
      posterior approach in upper extremity surgery and its effects on routine
      pulmonary function tests. METHODS: Interscalene block by posterior approach was
      performed with a peripheral nerve stimulator localization in 29 ASA Physical
      Status I and II patients undergoing upper extremity surgery. All patients were
      given 20 mL of 1% lidocaine and 20 mL of 0.5% bupivacaine. Modified Bromage Scale
      for motor block and pinprick test for sensory anesthesia was used. Pulmonary
      function, measurements [forced vital capacity (FVC), forced expiratory volume in
      1 second (FEV1), and VC (vital capacity)] were done in all patients just before
      and 2, 5, 10, 15, and 30 minutes after the block. RESULTS: Surgery location was
      the arm in four cases, and the forearm in 25 cases. General anesthesia was added
      in nine patients. Intravenous analgesics or sedatives were needed in four cases.
      Ulnar nerve was missed in 13 patients. FEV1 decreased 11.5% in 2 minutes (P >
      .05), 19.7% in 5 minutes (P = .0525), and FVC decreased 16.6% in 2 minutes (P >
      .05), 24.5% in 5 minutes after block (P < .05). CONCLUSIONS: Interscalene block
      by posterior approach did not provide a satisfactory anesthesia for forearm and
      hand surgery. This method also caused hemidiaphragmetic paresis and a reduction
      in pulmonary function tests as in the lateral approach of Winnie. We believe
      limitations and relative contraindications for interscalene block by lateral
      approach are the same for posterior approach.

PMID- 9552785
TI  - Sensory block extension during combined spinal and epidural.
AB  - BACKGROUND AND OBJECTIVES: During a combined spinal and epidural technique,
      extension of sensory block by epidural injection of saline or bupivacaine has
      been demonstrated and attributed to a volume effect or to the combination of a
      volume effect with a local anesthetic effect. This two-part study was designed to
      evaluate the time dependency of the volume effect and the local anesthetic effect
      on the mechanism of spinal block extension. METHODS: We performed two prospective
      studies. Thirty patients were randomized in each study. A combined spinal and
      epidural was performed in a sitting position in all groups. The patients in the
      first study received 15 mg hyperbaric bupivacaine intrathecally and were placed
      supine 2 minutes after spinal injection. They received 10 mL epidural saline
      either 5 minutes after spinal (group A) or 20 minutes after spinal (group B)
      compared to a control group (group C). The patients in the second study received
      12.5 mg hyperbaric bupivacaine intrathecally and were placed supine 5 minutes
      after spinal injection. They then received epidurally either 10 mL saline 7
      minutes after spinal (group D) or 10 mL bupivacaine 7 minutes after spinal (group
      E) or nothing (group F). Sensory block levels were assessed by a loss of
      sensation to cold using ether. RESULTS: In the first portion of this study, in
      group A, area under the curve of sensory block levels by time from 10 to 40
      minutes after spinal injection, and maximum sensory block levels were
      significantly higher (P < .05) compared to groups B and C. In the second portion
      of the study, sensory block levels were comparable at all times in the three
      groups. CONCLUSIONS: During a combined spinal and epidural technique with the use
      of hyperbaric bupivacaine, the volume effect is time dependent and is seen when
      epidural top up is done soon after spinal injection. This volume effect is
      abolished when patients are left seated for 5 minutes after spinal injection. The
      local anesthetic effect is not demonstrated when high sensory block levels are
      achieved by spinal injection.

PMID- 9552786
TI  - The use of 5% lidocaine for prolonged analgesia in chronic pain patients: a new
      technique.
AB  - BACKGROUND AND OBJECTIVES: It has been found that 5% lidocaine with 7.5% dextrose
      causes irreversible conduction block in animal studies. Our case report subjects
      allowed us to observe the efficacy of 5% lidocaine for a prolonged analgesia in
      vivo. METHOD: After performing a diagnostic nerve block with 1% lidocaine, 5%
      lidocaine with 7.5% dextrose was injected into three patients with trigeminal
      neuralgia, post-herpetic occipital neuralgia, and intercostal neuralgia,
      respectively. The patients were followed for one and a half years. Visual Analog
      Scale (VAS) scores and the side effects were recorded for each patient. RESULTS:
      One patient received a trigeminal block and one patient received an occipital
      nerve block. Both patients reported immediate and complete pain relief lasting 14
      and 8 months, respectively. One patient, given an intercostal nerve block,
      received immediate pain relief lasting 5 weeks. None of these patients exhibited
      any appreciable side effects or complications. CONCLUSIONS: Our observations
      suggest that 5% lidocaine may be used safely and effectively for the purpose of
      prolonged analgesia in selected patients with intractable chronic pain syndromes.

PMID- 9552787
TI  - An unusual cause of acute chest pain during epidural anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Selective sympathetic denervation during epidural
      anesthesia results in a small, active gut. These changes can also result in
      selective activity in one segment of the gut that is absent in other segments.
      CASE REPORT: A 61-year-old male was scheduled for bilateral total knee
      replacement during epidural anesthesia. Following onset of the epidural block, he
      experienced severe left-sided chest pain. Surgery was canceled. A portable chest
      radiograph revealed a widened mediastinum, and he underwent angiography to rule
      out a dissecting thoracic aortic aneurysm. The left subclavian artery could not
      be visualized, and an MRI was obtained, which was normal. After his return to the
      intensive care unit, he had a large bowel movement and his chest pain resolved.
      CONCLUSION: Selective activity of the gastrointestinal tract during the onset of
      epidural anesthesia created a visceral pain, which effectively simulated pain
      with a cardiovascular origin.

PMID- 9552788
TI  - Paraplegia following intracord injection during attempted epidural anesthesia
      under general anesthesia.
AB  - BACKGROUND AND OBJECTIVES: A case of permanent paraplegia is reported following
      attempted epidural anesthesia for a total knee replacement in a 62-year-old woman
      with a history of lumbar laminectomy for a prolapsed intervertebral disc.
      METHODS: Epidural puncture was attempted during general anesthesia and
      neuromuscular block. RESULTS: After four unsuccessful attempts, an epidural
      catheter was inserted above the upper end of the laminectomy scar. Several
      episodes of arterial hypotension occurred intraoperative and postoperative.
      Operative blood loss was minimal, and no bone glue was used. The patient awoke
      paraparetic with a sensory level of anesthesia to T5 bilaterally. MRI revealed an
      air bubble in the cord at T10 and a region of increased T2-weighted signal in the
      anterior aspect of the spinal cord between T4 and T5, consistent with infarction.
      CONCLUSION: Standards of management are discussed in relation to this case.

PMID- 9552789
TI  - The posterior epidural space depth.

PMID- 9552790
TI  - Regarding axillary and supraclavicular techniques of nerve block being described
      as approaches to brachial plexus.

PMID- 9552791
TI  - Case report on gabapentin.

PMID- 9552792
TI  - Combined spinal epidural (CSE) analgesia, fetal bradycardia, and uterine
      hypertonus.

PMID- 9552793
TI  - Regarding Dr. Steven's editorial.

PMID- 9552794
TI  - New treatments for schizophrenia--Part I.

PMID- 9552795
TI  - The many uses of interpersonal therapy.

PMID- 9552796
TI  - The seriousness of child's play.

PMID- 9552797
TI  - Breath of panic.

PMID- 9552798
TI  - Aggressive children and their self-esteem.

PMID- 9552799
TI  - Attention deficit and bad behavior.

PMID- 9552800
TI  - What becomes of aggressive school-children?

PMID- 9552801
TI  - A new take on prostate drugs.

PMID- 9552802
TI  - High-tech aid for your hearing.

PMID- 9552803
TI  - Outwitting three leading travel-health problems.

PMID- 9552804
TI  - Treating an underdiagnosed cause of headaches.

PMID- 9552805
TI  - Restoring sexuality after cancer.

PMID- 9552807
TI  - It is true that drinking soda increases my risk of osteoporosis?

PMID- 9552806
TI  - Is the new anti-obesity drug Meridia safer than fen-phen?

PMID- 9552808
TI  - Direct veneers: the clinical technique.

PMID- 9552809
TI  - Chewing gum and the dental health balance.

PMID- 9552810
TI  - Disinfection of impressions.

PMID- 9552811
TI  - Biological aspects of root canal filling materials-
      histocompatibility,cytotoxicity, and mutagenicity.
AB  - In order to minimize the incidence of local and/or systemic side effects, the
      biocompatibility of all endodontic materials should be investigated by various in
      vitro and in vivo tests prior to clinical application. The battery of in vitro
      tests includes determinations of mutagenicity, cytotoxicity, and antibacterial
      effects. Several reports have shown that paraformaldehyde-containing ZnO-eugenol
      cements in particular, such as Endomethasone and N2, are antibacterial. On the
      other hand, it has been found that endodontic materials with strong antimicrobial
      activity are frequently mutagenic, i.e., primarily those which release
      formaldehyde. Cell culture tests clearly show significantly different
      cytocompatibility of the various types of endodontic sealers: in general,
      formaldehyde-containing ZnO-eugenol cements are classified as highly/extremely
      cytotoxic, whereas most Ca(OH)2-based sealers are rated as possessing good or
      excellent cytocompatibility. These results were confirmed by numerous
      histological studies in vivo. Sealers with inferior biocompatibility, such as
      formaldehyde-releasing materials, should no longer be applied in practice because
      safer alternatives are available.

PMID- 9552812
TI  - The 5-year clinical performance of direct composite additions to correct tooth
      form and position. I. Esthetic qualities.
AB  - The aim of the study was to evaluate the esthetic performance of direct composite
      additions in correcting tooth form and position at 5 years. Composite additions
      were directly placed using the acid-etch technique and enamel bonding on 87
      intact maxillary anterior teeth in 23 young patients (12-19 years old). The
      restorations were made by one operator using an ultrafine midway-filled densified
      restorative composite. Color slides were made at baseline and 5 years. At the 5
      year recall, esthetic performance was assessed clinically by two evaluators at
      chair-side in subterms of color match, translucency/opacity, surface roughness,
      and anatomical form. Five additional examiners scored esthetics on the 5-year
      slides. Of the restorations, 89% were still esthetically satisfactory after 5
      years of clinical service. The remaining restorations needed replacement, mainly
      because of severe loss of anatomical form, to a lesser degree because of severe
      color mismatch. Central incisors and small unilateral restorations generally
      showed the best results concerning color match (68% and 74%, respectively) and
      surface smoothness (84% and 100%, respectively). The slide scores on color match
      and translucency/opacity were generally similar or somewhat better than the
      direct clinical scores; however, the difference were not statistically
      significant (P > 0.05). As far as surface roughness is concerned, the results
      were significantly better (P < 0.05) when recorded indirectly than by direct
      clinical evaluation. In conclusion, direct composite additions are a valuable and
      effective procedure for esthetic and conservative treatment of malformed and
      misaligned anterior teeth. Loss of anatomical form due to wear points to a
      shortcoming of the composite material used, with which a durable esthetic result
      cannot always be guaranteed in the long term.

PMID- 9552813
TI  - The 5-year clinical performance of direct composite additions to correct tooth
      form and position. II. Marginal qualities.
AB  - The aim of the study was to evaluate the marginal performance of direct composite
      additions for the correction of tooth form and position at 5 years. Composite
      additions were directly placed using the acid-etch technique and enamel bonding
      on 87 intact maxillary anterior teeth in 23 young patients (12-19 years old). The
      restorations were made by one operator using an ultrafine midway-filled densified
      restorative composite. Color slides were made at baseline and 5 years. At the 5
      year recall, marginal performance was assessed by two evaluators in terms of
      marginal adaptation and retention, clinical microleakage, and caries recurrence.
      Marginal adaptation and clinical microleakage were judged on the vestibular,
      palatal, and proximal planes. In addition, these planes were divided into a
      cervical and an incisal part. No caries recurrence was noted at 5 years and no
      restoration was lost. Concerning marginal adaptation, only four restorations (5%)
      presented a severe incisal chipping and needed replacement. The restorations
      showed a significantly (P < 0.05) higher percentage of perfect margins incisally
      (37%) than cervically (15%). Canines showed the best cervical marginal adaptation
      (29% with perfect margins), the best results being with small unilateral
      restorations. Concerning clinical microleakage, 7% of the restorations were rated
      as clinically unacceptable due to severe marginal discoloration. Clinical
      microleakage was significantly more often (P < 0.05) found among smokers. In
      conclusion, an ultrafine midway-filled densified composite is indicated for use
      in stress-bearing areas in the anterior region. The type and location of the
      restoration are determining factors for marginal integrity.

PMID- 9552814
TI  - Clinical evaluation of heat-pressed glass-ceramic inlays in vivo: 2-year results.
AB  - In the present study, the 2-year clinical and scanning electron microscope (SEM)
      results for heat-pressed ceramic inlays are reported. In a selected patient
      population, 51 cavities were restored with all-ceramic inlays. All margins were
      located within the enamel. The inlays were luted to the cavities with a high
      viscosity, dual-cure luting composite. After 2 days, 1 year, and 2 years, the
      restorations were evaluated clinically, using the modified USPHS criteria.
      Quantitative margin analysis was performed in the SEM on the replicas fabricated
      at the recall times. The data were tested for significant differences, using the
      chi-square test for the clinical evaluation and the Mann-Whitney U-test for the
      margin analysis. After 2 years, the clinical evaluation of the margin adaptation
      revealed Bravo ratings for 14 restorations (27.5%); 37 restorations (72.5%) were
      rated Alfa. Compared to the baseline data, this difference was statistically
      significant (p < or = 0.5). SEM analysis revealed that the ceramic-composite
      interface exhibited significantly (p < or = 0.01) more gap formation than the
      enamel-composite interface at all times of evaluation. Wear of the luting
      composite could be determined along 50% of the restoration interface during the
      first year, 53% during the second year. The inlay restorations controlled in this
      study perform well after a period of 2 years.

PMID- 9552815
TI  - Nifedipine pharmacological variables as risk factors for gingival overgrowth in
      organ-transplant patients.
AB  - The prevalence and severity of gingival overgrowth in organ-transplant patients
      medicated with cyclosporin are greater in patients concomitantly medicated with
      nifedipine; however, no relationship between the gingival overgrowth and any of
      the nifedipine pharmacological variables has been demonstrated. The study
      examined the effect of five nifedipine pharmacological variables (nifedipine
      dosage, plasma concentration and gingival crevicular fluid concentration, M1
      metabolite plasma concentration and the nifedipine: M1 ratio). The effect of the
      nifedipine variables on the gingival overgrowth score were examined using
      univariate and multivariate regression analysis. Adjustment for the effect of
      other risk factors was made by adding the distribution of each of the nifedipine
      variables in turn to a stepwise regression model containing previously identified
      risk factors for this condition. Despite the high levels of nifedipine
      sequestered in the GCF, only the plasma concentration of nifedipine was
      identified as a risk factor for the severity of gingival overgrowth in these
      patients (P = 0.01) once adjusted for other known risk factors (R2 for the model
      = 55%).

PMID- 9552816
TI  - Longevity of glass ceramic inlays and amalgam--results up to 6 years.
AB  - Ceramic inlays are discussed as one option for the substitution of amalgam
      restorations. The purpose of this study was to determine the longevity of glass
      ceramic inlays and amalgam restorations placed by the author: 123 class I and
      class II Dicor inlays placed with adhesive techniques and 163 amalgam class I and
      class II restorations were investigated. The observation time for the inlays
      varied from 4 to 82 months. The inlays were clinically investigated using
      modified USPHS criteria and documented photographically. Kaplan-Meier statistics
      were used to calculate the survival rate. From the 123 evaluated inlays 12 inlays
      (9.7%) failed: 7 due to fractures, 4 because of endodontic problems and 1 inlay
      was replaced due to persisting postoperative pain. All fractures could be
      explained by case selection errors. According to the Kaplan-Meier method, the
      estimated success rate after 6 years was 76% for the Dicor inlays and 87% for the
      amalgam restorations (control group). The difference was not statistically
      significant. It was concluded that Dicor inlays may be used as a successful
      alternative to amalgam.

PMID- 9552817
TI  - Miconazole lacquer in the treatment of denture stomatitis: clinical and
      microbiological findings in Chinese patients.
AB  - OBJECTIVE: To investigate the efficacy of a miconazole lacquer in producing
      mycological and clinical cure of Candida-associated denture stomatitis in a
      Chinese cohort and to study the microbiology of the conditions. DESIGN: A cross
      sectional study of the clinical and microbiological features of the condition and
      its response to treatment with the lacquer. SUBJECTS AND METHOD: Twenty-one
      Chinese adults with palatal erythema; 15 denture wearers matched for age and sex
      as controls for microbiology. Clinical examination, impression for culture,
      photograph of palate to monitor response to treatment, and lacquer application on
      upper denture base on days 0, 7 and 14. Impression and photograph repeated on day
      21; impression cultures quantified by image analysis. Palatal impression in
      controls; dummy impression as control for impression culture procedures. MAIN
      OUTCOME MEASURES: Severity of lesion, incidence and type of microorganism at
      presentation and during treatment; qualitative and quantitative assessment of
      yeast growth; the latter by statistical analysis of pixel units of yeast
      colonies; correlation of clinical and mycological cure. RESULTS: Out of the 21
      lesions (16 Newton's stage I and 5 stage II), 57% had yeasts at presentation, 10%
      coliforms and 33% no significant growth. Clinical cure in 3 weeks in 71%,
      mycological cure in 75% in 7 days; clinical and mycological cure coincided only
      in 43%. Polymicrobial growth of yeasts and coliforms throughout the course in
      some. CONCLUSIONS: Miconazole lacquer was a viable treatment option for Candida
      associated denture stomatitis in this adult, Chinese cohort; microbiology
      comprised yeasts, mainly C. albicans and coliforms, especially Klebsiella and
      Enterobacter species; the pathogenic role of the latter is questionable.

PMID- 9552818
TI  - Working parameters of a sonic scaler influencing root substance removal in vitro.
AB  - This study assessed defect depth and volume resulting from root instrumentation
      using a KaVo Sonic-flex Lux 2000 L sonic scaler with a slim scaling tip (Perio
      Tip no. 8) in vitro. Combinations of the following working parameters were
      analyzed: lateral forces of 0.5 N, 1 N, and 2 N; tip angulations of 0 degree, 45
      degrees, and 90 degrees; and instrumentation time of 10 s, 20 s, 40 s, and 80 s.
      Defects were quantified using a three-dimensional optical laser scanner.
      Instrumentation time had an almost linear impact on defect depth and volume.
      Although lateral force (beta-weight 0.55 +/- 0.062) had a greater influence on
      defect volume than tip angulation (beta-weight 0.29 +/- 0.062), their effects on
      defect depth were similar (beta-weight 0.43 +/- 0.052 and 0.50 +/- 0.052,
      respectively). The combination of force and angulation showed synergistic effects
      resulting in a wide range of defect depths (21.9 +/- 0.96 microns to 174 +/- 28.8
      microns, at 40 s) and volumes (0.056 +/- 0.019 mm3 to 0.68 +/- 0.10 mm3 at 40 s).
      Severe root damage (> 50 microns/40 s) did not occur at any combination of 0.5 N
      lateral force and/or 0 degree tip angulation. By adjusting lateral force and tip
      angulation, the efficacy of the assessed sonic scaler may be adapted to various
      clinical needs.

PMID- 9552819
TI  - Short-term assessment of leakage of Class V composite restorations placed in
      vivo.
AB  - The purpose of this study was to investigate the effectiveness of two dentin
      bonding systems, one of which was also in combination with a self-curing resin,
      when applied in V-shaped circular cavities cut in anterior teeth crossing the
      cementum-enamel junction. Twenty-seven teeth scheduled for extraction for
      periodontal reasons were treated in vivo. The sample teeth were divided at random
      into three groups. Group 1 was treated with All Bond 2 (AB2) + Z-100 composite,
      group 2 with Scotchbond Multipurpose Plus (SMPP) + Z-100, and group 3 with AB2 in
      conjunction with Bisfil 2B as liner and Z-100. The in vivo restored teeth were
      extracted after 2-3 months of clinical service. They were then immersed in a dye
      solution for 24 h, sectioned, and scored for marginal leakage. Analysis of
      variance revealed no significant differences between the three groups both at
      cervical and incisal sites. The enamel sites were free from any leakage. Only two
      cervical sites of groups 1 and 2 and one of group 3 showed a score 1 for leakage.
      The results of the short-term clinical performance of the three systems were
      promising.

PMID- 9552820
TI  - One-year clinical evaluation of composite fillings and inlays in posterior teeth.
AB  - In the course of a prospectively designed long-term clinical trial, composite
      fillings and inlays were evaluated for clinical acceptability as restorative
      materials in one, two or more surface cavities of posterior teeth over a 1-year
      period. In 45 patients, 88 restorations were placed by nine student operators,
      under the supervision of an experienced dentist, to compare the two half sides
      using the composite resins Tetric (Vivadent), blend-a-lux (Blend-a-med), and
      Pertac-Hybrid Unifil (Espe). The first clinical follow-up check took place within
      a time period of 11-13 months after placement of the restorations using modified
      USPHS criteria. The interpretation of the clinical criteria showed satisfactory
      results over this time period: more than 85% of the inlays and direct fillings
      were rated "alpha" or "bravo", using the parameters of assessment defined in this
      study. Only three restorations (two fillings, one inlay), all in molars, were
      rated "delta", i.e., unacceptable. The reasons for their replacement were
      marginal opening, secondary caries, and loss of sensitivity. For the criteria
      "surface texture", "anatomical form of the surface", and "occlusion", composite
      inlays were significantly better than composite fillings. These results indicate
      that posterior composite restorations provide acceptable and excellent clinical
      service, even if they are placed by relatively inexperienced student operators.

PMID- 9552821
TI  - Effectiveness of diamond-impregnated felt wheels for polishing a hybrid
      composite.
AB  - The effectiveness of diamond-impregnated felt wheels for polishing the surfaces
      of a fine-particle hybrid composite was studied in relation to different
      finishing methods. Standardised composite specimens were finished with one or a
      series of two or three finishing diamonds (particle size 30, 15 and 8 microns),
      one or two tungsten carbide finishing burs (12- and 30-fluted) or with a
      finishing diamond followed by a tungsten carbide bur. The final polishing of all
      specimens was done with the diamond-impregnated felt wheel Diafix alpha.
      Treatment with Sof-Lex discs after the use of a finishing diamond served as a
      polishing standard for comparison. Evaluation of the final surfaces was done with
      profilometry and by scanning electron microscopy. The profilometric results
      showed that the type of pretreatment was decisive for the quality of the final
      polishing. Nearly all surfaces polished by the diamond-impregnated felt wheels
      were smoother than those treated by the flexible discs (P < 0.01). The lowest
      roughness data were recorded following a pretreatment with a finishing diamond
      and a tungsten carbide finishing bur. After appropriate pretreatment, the hybrid
      composite surface was sufficiently polished with the diamond-impregnated felt
      wheels.

PMID- 9552822
TI  - A microbiological study of pre- and postoperative apicoectomy sites.
AB  - There is little information on the microbiology of periapical lesions, and no
      data on the residual microbial flora in the periapex, if any, after apicoectomy
      procedures. Hence, 64 patients treated by apicoectomy procedures were
      prospectively studied to assess the bacterial flora in the periapex and to
      evaluate the residual bacteria in postoperative apicoectomy sites. Of the 64
      lesions studied, 14 (22%) were sterile and 50 (78%) yielded bacteria
      preoperatively. Bacteria could be recovered from 28 (56%) of the latter lesions
      after apicoectomy and curettage. A total of 105 bacterial strains was isolated
      from 50 lesions, yielding a range of 1-4 (mean 2.1) species per sample. The
      isolates comprised 84 (80%) facultative anaerobes and 21 (20%) strict anaerobes.
      A polymicrobial growth was obtained from 39 lesions whilst 11 lesions yielded
      pure cultures. On detailed microbiological analyses of 29 lesions, 40% of the
      isolates were identified as alpha-haemolytic streptococci, half of which were
      Streptococcus sanguis; anaerobic streptococci were the predominant anaerobes.
      None of the organisms or group(s) of organisms emerged as recalcitrant colonisers
      which were difficult to dislodge after surgical debridement. These data indicate
      that the majority of periapical lesions harbour a variety of flora which cannot
      be eradicated despite thorough apicoectomy procedures.

PMID- 9552823
TI  - A randomised clinical trial on the influence of splinted and unsplinted oral
      implants in mandibular overdenture therapy. A 3-year report.
AB  - A randomised clinical trial was performed to investigate whether there is a need
      or advantage to splint two implants in the mandible retaining a hinging
      overdenture. Furthermore, patient satisfaction was evaluated for different
      attachment systems retaining the overdenture. Thirty-six edentulous patients were
      randomised into three groups of equal size and treated with either magnets, ball
      attachments or straight bars (reference group). After 3 years of observation no
      implants were lost in any of the groups. Besides, no statistically significant
      differences were noted for the peri-implant outcome. Although the bar group
      presented the highest retention force, the general satisfaction of the patients
      in the three groups did not differ. The patients with bar retentions showed less
      prosthetic complications of the retention elements but more at the level of the
      denture-supporting mucosa. Finally, the clinical outcome of all groups confirms
      that overdenture treatment demands regular controls with limited time intervals.

PMID- 9552824
TI  - The stereognostic ability of natural dentitions versus implant-supported fixed
      prostheses or overdentures.
AB  - A stereognostic ability test was performed in 60 patients. Forty patients were
      rehabilitated by means of osseointegrated implants. One group consisted of 20
      patients with fixed prostheses on implants in both the upper and lower jaws. The
      other 20 patients had a maxillary denture while in the mandible an overdenture
      was retained by means of two implants connected by a bar. They were compared to a
      group of 20 subjects (controls) with a non-restored natural dentition. For the
      stereognostic ability test, subjects had to recognise ten different test pieces
      by manipulating them with two antagonistic incisor teeth, avoiding any contact
      with other oral structures. Both response time and percentage accuracy of
      recognition were evaluated. The present findings indicated that subjects with an
      overdenture on implants did not score significantly different from those with an
      implant-supported fixed prosthesis. In contrast, subjects with teeth had a
      significantly better stereognostic ability. The percentage of correct responses
      was 52% for overdentures, 56% for fixed prostheses on implants and 75% for
      natural dentitions. From these results, it could be concluded that the
      stereognostic ability is impaired in subjects rehabilitated with osseointegrated
      implants by about one-third to one-quarter compared to subjects with natural
      teeth.

PMID- 9552825
TI  - In vivo study on the effectiveness of a lacquer containing CaF2/NaF in treating
      dentine hypersensitivity.
AB  - The purpose of this double-blind study was to evaluate the effectiveness of a
      commercially available fluoride lacquer (Bifluorid 12) containing CaF2 (6%) and
      NaF (6%) in reducing dentine hypersensitivity. A fluoride lacquer containing only
      NaF (6%) served as a control. Twenty-five adult patients complaining about at
      least two hypersensitive teeth participated in this study. In each patient and at
      each appointment, one tooth was treated with Bifluorid 12, while the other was
      treated with the control substance. Sensitivity levels were determined before and
      after the application of each lacquer at baseline as well as at 1, 2 and 3 weeks
      after the start of study. The final evaluation of hypersensitivity was performed
      at 4 weeks, and follow-ups were undertaken at 6 and 12 months. A reproducible air
      blast stimulus and a visual analogue scale were used for evaluation. Results
      demonstrated a distinct reduction of hypersensitivity after 1, 2 and 3 weeks in
      the Bifluorid 12 group. Initially, no obvious effects could be observed in the
      control group. However, a clear alleviation could be observed after 2 and 3 weeks
      with the control. After 4 weeks, the overall sensitivity scores were comparably
      low, without any significant differences between the two fluoride lacquers. In
      both groups, the effects of treatment were seen over the 12-month observation
      period. Bifluorid 12 was considered at least comparable to the control. It is
      concluded from this study that Bifluorid 12 is effective in the initial reduction
      of dentine hypersensitivity. The combination of CaF2/NaF can be recommended for
      clinical use.

PMID- 9552827
TI  - Effects of 15% oxygen on breathing patterns and oxygenation in infants.

PMID- 9552828
TI  - Children in the mountains.

PMID- 9552829
TI  - Why doesn't audit work?

PMID- 9552830
TI  - Collapse reactions after whole cell pertussis vaccination.

PMID- 9552831
TI  - Simian virus 40 and human malignancy.

PMID- 9552832
TI  - Training in advanced trauma life support.

PMID- 9552833
TI  - Tackling violence.

PMID- 9552834
TI  - Cancer in parents: telling children.

PMID- 9552835
TI  - Effect of exposure to 15% oxygen on breathing patterns and oxygen saturation in
      infants: interventional study.
AB  - OBJECTIVE: To assess the response of healthy infants to airway hypoxia (15%
      oxygen in nitrogen). DESIGN: Interventional study. SETTINGS: Infants' homes and
      paediatric ward. SUBJECTS: 34 healthy infants (20 boys) born at term; mean age at
      study 3.1 months. 13 of the infants had siblings whose deaths had been ascribed
      to the sudden infant death syndrome. INTERVENTION: Respiratory variables were
      measured in room air (pre-challenge), while infants were exposed to 15% oxygen
      (challenge), and after infants were returned to room air (post-challenge). MAIN
      OUTCOME MEASURES: Baseline oxygen saturation as measured by pulse oximetry,
      frequency of isolated and periodic apnoea, and frequency of desaturation (oxygen
      saturation < or = 80% for > or = 4 s). Exposure to 15% oxygen was terminated if
      oxygen saturation fell to < or = 80% for > or = 1 min. RESULTS: Mean duration of
      exposure to 15% oxygen was 6.3 (SD 2.9) hours. Baseline oxygen saturation fell
      from a median of 97.6% (range 94.0% to 100%) in room air to 92.8% (84.7% to 100%)
      in 15% oxygen. There was no correlation between baseline oxygen saturation in
      room air and the extent of the fall in baseline oxygen saturation on exposure to
      15% oxygen. During exposure to 15% oxygen there was a reduction in the proportion
      of time spent in regular breathing pattern and a 3.5-fold increase in the
      proportion of time spent in periodic apnoea (P < 0.001). There was an increase in
      the frequency of desaturation from 0 episodes per hour (range 0 to 0.2) to 0.4
      episodes per hour (0 to 35) (P < 0.001). In 4 infants exposure to hypoxic
      conditions was ended early because of prolonged and severe falls in oxygen
      saturation. CONCLUSIONS: A proportion of infants had episodes of prolonged (< or
      = 80% for > or = 1 min) or recurrent shorter (< or = 80% for > or = 4 s)
      desaturation, or both, when exposed to airway hypoxia. The quality and quantity
      of this response was unpredictable. These findings may explain why some infants
      with airway hypoxia caused by respiratory infection develop more severe
      hypoxaemia than others. Exposure to airway hypoxia similar to that experienced
      during air travel or on holiday at high altitude may be harmful to some infants.

PMID- 9552837
TI  - Mental health problems of homeless children and families: longitudinal study.
AB  - OBJECTIVE: To establish the mental health needs of homeless children and families
      before and after rehousing. DESIGN: Cross sectional, longitudinal study. SETTING:
      City of Birmingham. SUBJECTS: 58 rehoused families with 103 children aged 2-16
      years and 21 comparison families of low socioeconomic status in stable housing,
      with 54 children. MAIN OUTCOME MEASURES: Children's mental health problems and
      level of communication; mothers' mental health problems and social support one
      year after rehousing. RESULTS: Mental health problems remained significantly
      higher in rehoused mothers and their children than in the comparison group
      (mothers 26% v 5%, P = 0.04; children 39% v 11%, P = 0.0003). Homeless mothers
      continued to have significantly less social support at follow up. Mothers with a
      history of abuse and poor social integration were more likely to have children
      with persistent mental health problems. CONCLUSIONS: Homeless families have a
      high level of complex needs that cannot be met by conventional health services
      and arrangements. Local strategies for rapid rehousing into permanent
      accommodation, effective social support and health care for parents and children,
      and protection from violence and intimidation should be developed and
      implemented.

PMID- 9552838
TI  - Rate of recurrent collapse after vaccination with whole cell pertussis vaccine:
      follow up study.

PMID- 9552839
TI  - Phantom pain, anxiety, depression, and their relation in consecutive patients
      with amputated limbs: case reports.

PMID- 9552841
TI  - What's a network?

PMID- 9552840
TI  - Influence of travel patterns on mortality from injury among teenagers in England
      and Wales, 1985-95: trend analysis.

PMID- 9552842
TI  - Quantitative systematic review of randomised controlled trials comparing
      antibiotic with placebo for acute cough in adults.
AB  - OBJECTIVES: To assess whether antibiotic treatment for acute cough is effective
      and to measure the side effects of such treatment. DESIGN: Quantitative
      systematic review of randomised placebo controlled trials. DATA SOURCES: Nine
      trials (8 published, 1 unpublished) retrieved from a systematic search
      (electronic databases, contact with authors, contact with drug manufacturers,
      reference lists); no restriction on language. MAIN OUTCOME MEASURES: Proportion
      of subjects with productive cough at follow up (7-11 days after consultation with
      general practitioner); proportion of subjects who had not improved clinically at
      follow up; proportion of subjects who reported side effects from taking
      antibiotic or placebo. RESULTS: Eight trials contributed to the meta-analysis.
      Resolution of cough was not affected by antibiotic treatment (relative risk 0.85
      (95% confidence interval 0.73 to 1.00)), neither was clinical improvement at re
      examination (relative risk 0.62 (0.36 to 1.09)). The side effects of antibiotic
      were more common in the antibiotic group when compared to placebo (relative risk
      1.51 (0.86 to 2.64)). CONCLUSIONS: Treatment with antibiotic does not affect the
      resolution of cough or alter the course of illness. The benefits of antibiotic
      treatment are marginal for most patients with acute cough and may be outweighed
      by the side effects of treatment.

PMID- 9552843
TI  - Recent advances. Cardiology.

PMID- 9552844
TI  - Haemochromatosis as an endocrine cause of subfertility.

PMID- 9552845
TI  - Caffeine and canine

PMID- 9552847
TI  - Unequal encounter

PMID- 9552846
TI  - ABC of allergies. Perennial rhinitis.

PMID- 9552848
TI  - Sex, drugs, and the invasion of privacy

PMID- 9552850
TI  - Supermarket cigarettes: the brands that dare not speak their name.

PMID- 9552849
TI  - Urgency and priority for cardiac surgery: a clinical judgment analysis.

PMID- 9552851
TI  - Coping with loss. Bereavement in childhood.

PMID- 9552852
TI  - Fast track admission for children with sickle cell crises. Should morphine or
      pethidine be given?

PMID- 9552854
TI  - Management of aseptic meningitis secondary to intravenous immunoglobulin.

PMID- 9552853
TI  - Management of sickle cell disease. Non-addictive analgesics can be as effective
      as morphine and pethidine.

PMID- 9552855
TI  - Coordinated neonatal screening programme for haemoglobin disorders is needed.

PMID- 9552857
TI  - Doctors are not pressured into giving prescriptions.

PMID- 9552858
TI  - Article showed how not to read economic evaluations.

PMID- 9552859
TI  - Use of lasers can cause visual impairment

PMID- 9552861
TI  - Resource allocation to health authorities. Expenditure on private health care
      must be taken into account

PMID- 9552860
TI  - Separate R&D budget is needed for monitoring effects of new drugs

PMID- 9552863
TI  - BMA cannot bring proceedings arising out of incidents in other countries

PMID- 9552862
TI  - New biomolecular assays must be tested by direct study in the developing world.

PMID- 9552865
TI  - Health secretary wants to work with clinicians

PMID- 9552864
TI  - Isidor ("Okkie") Gordon

PMID- 9552866
TI  - Selling out

PMID- 9552867
TI  - Just another Sunday

PMID- 9552868
TI  - The hot air on passive smoking

PMID- 9552869
TI  - Developing Professional Judgement in Health Care

PMID- 9552870
TI  - Mass Listeria: The Meaning of Health Scares

PMID- 9552872
TI  - Folic acid and vitamin B-12 and B-6 supplements reduce blood homocysteine
      concentrations

PMID- 9552871
TI  - Some infants develop hypoxaemia when breathing 15% oxygen

PMID- 9552874
TI  - "Collapse" after pertussis vaccination does not recur after subsequent doses

PMID- 9552873
TI  - Psychosocial problems continue in homeless families after rehousing

PMID- 9552875
TI  - Phantom limb pain is not a sign of grief

PMID- 9552876
TI  - Antibiotics are unlikely to alter clinical course of acute cough

PMID- 9552878
TI  - Good engineering is not good medicine

PMID- 9552877
TI  - Good engineering is not good medicine

PMID- 9552879
TI  - Blood products produced from plasma from donors in UK are still being made

PMID- 9552880
TI  - Patients offered treatment for CHD need full information to make decision

PMID- 9552881
TI  - Publication of pictures of patient on BMJ's website was mistake

PMID- 9552883
TI  - Task force will involve NHS staff

PMID- 9552882
TI  - Flora Bridge

PMID- 9552884
TI  - Mistakes

PMID- 9552885
TI  - Most patients don't read the BMJ Editorial by Smith and Education and debate pp
      1000-11

PMID- 9552886
TI  - Nuchal translucency-screening without consent

PMID- 9552887
TI  - What Are Doctors For?

PMID- 9552888
TI  - Specialist Outreach Clinics in General Practice

PMID- 9552889
TI  - The Pocket Guide to Grant Applications

PMID- 9552890
TI  - The Mad Cow Crisis: Health and the Public Good

PMID- 9552891
TI  - Colloids no better than crystalloids for fluid replacement in hypovolaemic
      patients

PMID- 9552893
TI  - Heparin (1 U/ml) flushes of peripheral venous catheters prolongs their potency

PMID- 9552892
TI  - Inpatient and day care are equally good in acute rheumatoid arthritis

PMID- 9552894
TI  - Use of magnesium in pre-eclampsia is growing

PMID- 9552895
TI  - Understanding patients' cultural beliefs helps health providers serve them better

PMID- 9552896
TI  - Epidemiological data are of little use in guiding clinical practice

PMID- 9552897
TI  - Cardiac arrests outside hospital.

PMID- 9552898
TI  - Shifts in opportunities for doctors in training.

PMID- 9552899
TI  - Protecting the public from risk of harm.

PMID- 9552900
TI  - Cannabis as medicine: time for the phoenix to rise?

PMID- 9552901
TI  - Equity on both the scientific and the policy agendas.

PMID- 9552902
TI  - Unscientific practice flourishes in science.

PMID- 9552903
TI  - Smoking and risk of myocardial infarction in women and men: longitudinal
      population study.
AB  - OBJECTIVE: To compare risk of myocardial infarction associated with smoking in
      men and women, taking into consideration differences in smoking behaviour and a
      number of potential confounding variables. DESIGN: Prospective cohort study with
      follow up of myocardial infarction. SETTING: Pooled data from three population
      studies conducted in Copenhagen. SUBJECTS: 11,472 women and 13,191 men followed
      for a mean of 12.3 years. MAIN OUTCOME MEASURES: First admission to hospital or
      death caused by myocardial infarction. RESULTS: 1251 men and 512 women had a
      myocardial infarction during follow up. Compared with non-smokers, female current
      smokers had a relative risk of myocardial infarction of 2.24 (range 1.85-2.71)
      and male smokers 1.43 (1.26-1.62); ratio 1.57 (1.25-1.97). Relative risk of
      myocardial infarction increased with tobacco consumption in both men and women
      and was higher in inhalers than in non-inhalers. The risks associated with
      smoking, measured by both current and accumulated tobacco exposure, were
      consistently higher in women than in men and did not depend on age. This sex
      difference was not affected by adjustment for arterial blood pressure, total and
      high density lipoprotein cholesterol concentrations, triglyceride concentrations,
      diabetes, body mass index, height, alcohol intake, physical activity, and level
      of education. CONCLUSION: Women may be more sensitive than men to some of the
      harmful effects of smoking. Interactions between components of smoke and hormonal
      factors that may be involved in development of ischaemic heart disease should be
      examined further.

PMID- 9552904
TI  - Ecological study of reasons for sharp decline in mortality from ischaemic heart
      disease in Poland since 1991.
AB  - OBJECTIVE: To investigate the reasons for the decline in deaths attributed to
      ischaemic heart disease in Poland since 1991 after two decades of rising rates.
      DESIGN: Recent changes in mortality were measured as percentage deviations in
      1994 from rates predicted by extrapolation of sex and age specific death rates
      for 1980-91 for diseases of the circulatory system and selected other categories.
      Available data on national and household food availability, alcohol consumption,
      cigarette smoking, socioeconomic indices, and medical services over time were
      reviewed. MAIN OUTCOME MEASURES: Age specific and age standardised rates of death
      attributed to ischaemic heart disease and related causes. RESULTS: The change in
      trend in mortality attributed to diseases of the circulatory system was similar
      in men and women and most marked (> 20%) in early middle age. For ages 45 to 64
      the decrease was greatest for deaths attributed to ischaemic heart disease and
      atherosclerosis (around 25%) and less for stroke (< 10%). For most of the
      potentially explanatory variables considered, there were no corresponding changes
      in trend. However, between 1986-90 and 1994 there was a marked switch from animal
      fats (estimated availability down 23%) to vegetable fats (up 48%) and increased
      imports of fruit. CONCLUSION: Reporting biases are unlikely to have exaggerated
      the true fall in ischaemic heart disease; neither is it likely to be mainly due
      to changes in smoking, drinking, stress, or medical care. Changes in type of
      dietary fat and increased supplies of fresh fruit and vegetables seem to be the
      best candidates.

PMID- 9552905
TI  - Point of care testing: randomised controlled trial of clinical outcome.
AB  - OBJECTIVES: To describe the proportion of patients attending an accident and
      emergency department for whom blood analysis at the point of care brought about a
      change in management; to measure the extent to which point of care testing
      resulted in differences in clinical outcome for these patients when compared with
      patients whose samples were tested by the hospital laboratory. DESIGN: Open,
      single centre, randomised controlled trial. Blood samples were randomly allocated
      to point of care testing or testing by the hospital's central laboratory.
      SETTING: The accident and emergency department of the Bristol Royal Infirmary, a
      large teaching hospital which cares for an inner city population. SUBJECTS:
      Representative sample of patients who attended the department between April 1996
      and April 1997 and who required blood tests. Data collection was structured in 8
      hour blocks so that all hours of the day and all days of the week were equally
      represented. MAIN OUTCOME MEASURES: The proportion of patients for whom point of
      care testing brought about a change in treatment in which timing was considered
      to be critical to clinical outcome. Mortality, the length of stay in hospital,
      admission rate, the amount of time spent waiting for results of blood tests, the
      amount of time taken to decide on management plans, and the amount of time
      patients spent in the department were compared between patients whose samples
      were tested at the point of care and those whose samples were sent to the
      laboratory. RESULTS: Samples were obtained from 1728 patients. Changes in
      management in which timing was considered to be critical occurred in 59 out of
      859 (6.9%, 95% confidence interval 5.3% to 8.8%) patients in the point of care
      arm of the trial. Decisions were made 74 minutes earlier (68 min to 80 min, P <
      0.0001) when point of care testing was used for haematological tests as compared
      to central laboratory testing, 86 minutes earlier (80 min to 92 min, P < 0.0001)
      for biochemical tests, and 21 minutes earlier (-3 min to 44 min, P = 0.09) for
      analyses of arterial blood gases. There were no differences between the groups in
      the amount of time spent in the department, length of stay in hospital, admission
      rates, or mortality. CONCLUSION: Point of care testing reduced the time taken to
      make decisions on patient management that were dependent on the results of blood
      tests. It also brought about faster changes in treatment for which timing was
      considered to be critical in about 7% of patients. These changes did not affect
      clinical outcome or the amount of time patients spent in the department.

PMID- 9552906
TI  - Aspirin for prophylaxis against headache at high altitudes: randomised, double
      blind, placebo controlled trial.

PMID- 9552907
TI  - Prevalence of inflammatory bowel disease in British 26 year olds: national
      longitudinal birth cohort.

PMID- 9552908
TI  - Alternative definitions

PMID- 9552909
TI  - Patients' action during their cardiac event: qualitative study exploring
      differences and modifiable factors.
AB  - OBJECTIVES: To explore the circumstances and factors that explain variations in
      response to a cardiac event and to identify potentially modifiable factors.
      DESIGN: Qualitative analysis of semistructured, face to face interviews with
      patients admitted to two district hospitals for a cardiac event and with other
      people present at the time of the event. Patients were divided into three groups
      according to the length of delay between onset of symptoms and calling for
      medical help. SUBJECTS: 43 patients and 21 other people present at the time of
      the cardiac event. Patients were divided into three groups according to the
      length of time between onset of symptoms and seeking medical help: non-delayers
      (< 4 h; n = 21), delayers (4-12 h; n = 12), and extended delayers (> 12 h; n =
      10). MAIN OUTCOME MEASURES: Decision making process, strategies for dealing with
      symptoms, and perception of risk and of heart attacks before the event according
      to delay in seeking help. RESULTS: The illness and help seeking behaviour of
      informants had several components, including warning, interpretation, preliminary
      action, re-evaluation, and final action stages. The length of each stage was
      variable and depended on the extent to which informants mobilised and integrated
      resources into a strategy to bring their symptoms under control. There were
      obvious differences in informants' knowledge of the symptoms that they associated
      with a heart attack before the event. Non-delayers described a wider range of
      symptoms before their heart attack and twice as many (13) considered themselves
      to be potentially at risk of a heart attack compared with the other two groups.
      For most informants the heart attack differed considerably from their concept of
      a heart attack. CONCLUSION: The most critical factor influencing the time between
      onset of symptoms and calling for professional medical help is that patients and
      others recognise their symptoms as cardiac in origin. This study suggests that
      various points of intervention in the decision making process could assist
      symptom recognition and therefore faster access to effective treatment.

PMID- 9552911
TI  - The Nobel prizes

PMID- 9552910
TI  - Fatality outside hospital from acute coronary events in three British health
      districts, 1994-5. United Kingdom Heart Attack Study Collaborative Group.
AB  - OBJECTIVES: To provide a contemporary account of the treatment and outcomes of
      acute coronary attacks in England and Wales and to identify strategies that might
      improve the outcome. DESIGN: Two year community and hospital based study in three
      British health districts. SETTING: Health districts of Brighton (population
      282,000), South Glamorgan (408,000), and York (264,000). SUBJECTS: 3523 men and
      women under 75 years of age who died outside hospital from acute coronary causes,
      who were admitted to hospital with acute myocardial infarction, or who developed
      acute infarction or died unexpectedly from acute coronary causes while they were
      already in hospital. INTERVENTIONS: Attempted resuscitation in people having a
      cardiac arrest outside hospital. MAIN OUTCOME MEASURES: Total case fatality, case
      fatality outside and inside hospital, and the effect of resuscitation on case
      fatality outside hospital. RESULTS: 1589 patients died within 30 days of the
      acute event. Case fatality was 45% (95% confidence interval 43% to 47%), rising
      from 27% (160/595) (23% to 31%) at age < 55 years to 53% (1019/1916) (51% to 55%)
      at 65-74 years. Overall, 74% (1172/1589) (72% to 76%) of fatal events happened
      outside hospital, and there was a negative age gradient (P < 0.001) such that 91%
      (145/160) (87% to 95%) of fatalities occurred outside hospital at age < 55
      compared with 70% (710/1019) (67% to 73%) at 65-74 years. Without successful
      resuscitation of 55 patients outside hospital, total case fatality at 30 days
      would have risen from 45% to 46.7%. CONCLUSION: Opportunities for reducing
      fatality from acute coronary attacks lie mainly outside hospital. These results
      and others imply that survival from cardiac arrest outside hospital might be
      trebled by improved ambulance and patient response. Proper application of
      secondary preventive measures for patients with coronary disease could have an
      even larger impact.

PMID- 9552913
TI  - ABC of allergies. Avoiding exposure to indoor allergens.

PMID- 9552912
TI  - Accident and emergency medicine.

PMID- 9552914
TI  - The accurate use of language

PMID- 9552915
TI  - Misleading, unscientific, and unjust: the United Kingdom's research assessment
      exercise.

PMID- 9552916
TI  - Cambodia--after the killing fields.

PMID- 9552918
TI  - Reserve may be just another word for cowardice.

PMID- 9552917
TI  - Surgery and loss of body parts.

PMID- 9552919
TI  - Intravascular volume optimisation during repair of proximal femoral fracture.
      Intravascular volume was depleted perioperatively in control group

PMID- 9552921
TI  - Working in management. NHS managers have fundamental duty to put patients first.

PMID- 9552920
TI  - Oral contraception was not associated with venous thromboembolic disease in
      recent study.

PMID- 9552922
TI  - New method of expressing survival in cancer is popular.

PMID- 9552923
TI  - Drug and Therapeutics Bulletin defends its stance over donepezil

PMID- 9552924
TI  - Rationing health care. Patients need to be prioritised

PMID- 9552925
TI  - Breast feeding does not always work. Author should have felt angry rather than
      guilty.

PMID- 9552926
TI  - Human Fertility and Embryology Act 1990 discriminates against children. Children
      must not be denied future choice of using their gametes.

PMID- 9552928
TI  - James Seeds Naunton Briggs

PMID- 9552927
TI  - Refugee doctors face enormous difficulty.

PMID- 9552929
TI  - Doctors should have more input into merit award system

PMID- 9552930
TI  - Pray silence

PMID- 9552931
TI  - Painful decisions

PMID- 9552932
TI  - Death on camera.

PMID- 9552934
TI  - The Progress of Experiment: Science and Therapeutic Reform in the United States,
      1900-1990

PMID- 9552933
TI  - Principles and Practice of Critical Care

PMID- 9552935
TI  - Women who smoke have a greater risk of myocardial infarction than men who smoke

PMID- 9552936
TI  - Fall in coronary deaths in Poland may be linked to lower meat and butter intake

PMID- 9552937
TI  - Point of care testing improves process but not outcome in patients in A and E

PMID- 9552938
TI  - People need to recognise cardiac symptoms to reduce delay in receiving
      thrombolysis

PMID- 9552939
TI  - Death rates from heart attacks continue to be high outside hospital

PMID- 9552940
TI  - Prevalence of inflammatory bowel disease is rising in Britain

PMID- 9552941
TI  - Protecting breast feeding from breast milk substitutes.

PMID- 9552942
TI  - Neurological channelopathies.

PMID- 9552943
TI  - Antidepressant discontinuation reactions.

PMID- 9552944
TI  - Doctors in training: wasteful and inefficient?

PMID- 9552945
TI  - Rehabilitation for older people.

PMID- 9552946
TI  - The BMJ's website scales up.

PMID- 9552947
TI  - Violations of the international code of marketing of breast milk substitutes:
      prevalence in four countries.

PMID- 9552948
TI  - Open randomised study of use of levonorgestrel releasing intrauterine system as
      alternative to hysterectomy.
AB  - OBJECTIVES: To assess whether the levonorgestrel intrauterine system could
      provide a conservative alternative to hysterectomy in the treatment of excessive
      uterine bleeding. DESIGN: Open randomised multicentre study with two parallel
      groups: a levonorgestrel intrauterine system group and a control group. SETTING:
      Gynaecology departments of three hospitals in Finland. SUBJECTS: Fifty six women
      aged 33-49 years scheduled to undergo hysterectomy for treatment of excessive
      uterine bleeding. INTERVENTIONS: Women were randomised either to continue with
      their current medical treatment or to have a levonorgestrel intrauterine system
      inserted. MAIN OUTCOME MEASURE: Proportion of women cancelling their decision to
      undergo hysterectomy. RESULTS: At 6 months, 64.3% (95% confidence interval 44.1
      to 81.4%) of the women in the levonorgestrel intrauterine system group and 14.3%
      (4.0 to 32.7%) in the control group had cancelled their decision to undergo
      hysterectomy (P < 0.001). CONCLUSIONS: The use of the levonorgestrel intrauterine
      system is a good conservative alternative to hysterectomy in the treatment of
      menorrhagia and should be considered before hysterectomy or other invasive
      treatments.

PMID- 9552949
TI  - Baseline serum cholestanol as predictor of recurrent coronary events in subgroup
      of Scandinavian simvastatin survival study. Finnish 4S Investigators.

PMID- 9552950
TI  - Risk factors for coronary heart disease and infection with Helicobacter pylori:
      meta-analysis of 18 studies.

PMID- 9552951
TI  - Growth hormone as a risk for premature mortality in healthy subjects: data from
      the Paris prospective study.

PMID- 9552953
TI  - Randomised controlled trial of the READER method of critical appraisal in general
      practice.
AB  - OBJECTIVE: To evaluate the READER model for critical reading by comparing it with
      a free appraisal, and to explore what factors influence different components of
      the model. DESIGN: A randomised controlled trial in which two groups of general
      practitioners assessed three papers from the general practice section of the BMJ.
      SETTING: Northern Ireland. SUBJECTS: 243 general practitioners. MAIN OUTCOME
      MEASURES: Scores given using the READER model (Relevance, Education,
      Applicability, Discrimination, overall Evaluation) and scores given using a free
      appraisal for scientific quality and an overall total. RESULTS: The hierarchical
      order for the three papers was different for the two groups, according to the
      total scores. Participants using the READER method (intervention group) gave a
      significantly lower total score (P < or = 0.01) and a lower score for the
      scientific quality (P < or = 0.0001) for all three papers. Overall more than one
      in five (22%), and more men than women, read more than 5 articles a month (P < or
      = 0.05). Those who were trainers tended to read more articles (P < or = 0.05),
      and no trainers admitted to reading none. Overall, 58% (135/234) (68% (76/112) of
      the intervention group) believed that taking part in the exercise would encourage
      them to be more critical of published articles in the future (P < or = 0.01).
      CONCLUSION: Participants using the READER model gave a consistently lower overall
      score and applied a more appropriate appraisal to the methodology of the studies.
      The method was both accurate and repeatable. No intrinsic factors influenced the
      scores, so the model is appropriate for use by all general practitioners
      regardless of their seniority, location, teaching or training experience, and the
      number of articles they read regularly.

PMID- 9552954
TI  - Randomised comparison of cost effectiveness of guided self management and
      traditional treatment of asthma in Finland.

PMID- 9552957
TI  - ABC of allergies. Allergy and the skin. I--Urticaria.

PMID- 9552956
TI  - The role of nuclear medicine in clinical investigation.

PMID- 9552959
TI  - Ethics and evidence based medicine.

PMID- 9552960
TI  - Framework for analysing risk and safety in clinical medicine.

PMID- 9552961
TI  - Reducing the risk of nosocomial HIV infection in British health workers working
      overseas: role of post-exposure prophylaxis.

PMID- 9552962
TI  - Blindness and loss of other sensory and cognitive functions.

PMID- 9552965
TI  - Many climate change scientists do not agree that global warming is happening.

PMID- 9552970
TI  - Culyer reforms will create new opportunities for research.

PMID- 9552968
TI  - Medline and Embase complement each other in literature searches.

PMID- 9552973
TI  - Basing resource allocation formulas on standardised mortality ratios would be
      wrong.

PMID- 9552975
TI  - More patients should be excluded from being tissue donors.

PMID- 9552976
TI  - Acute excited states and sudden death. Death after restraint can be avoided.

PMID- 9552989
TI  - Routine episiotomy in developing countries. Time to change a harmful practice.

PMID- 9552990
TI  - Long term pharmacotherapy of depression. Can reduce relapses and recurrences in
      major depression.

PMID- 9552991
TI  - Tamoxifen for the prevention of breast cancer. Important questions remain
      unanswered, and existing trials should continue.

PMID- 9552992
TI  - Selegiline, or the problem of early termination of clinical trials. The clinical
      questions are not well answered, and probably never will be.

PMID- 9552993
TI  - Monitoring randomised controlled trials. Parkinson's disease trial illustrates
      the dangers of stopping early.

PMID- 9552994
TI  - Why do children have chronic abdominal pain, and what happens to them when they
      grow up? Population based cohort study.
AB  - OBJECTIVE: To test the hypotheses that children with abdominal pain have anxious
      parents and come from families with high rates of physical illness and that they
      grow up to suffer from high rates of medically unexplained symptoms and
      psychiatric disorders. DESIGN: Population based birth cohort study. SETTING:
      General population. SUBJECTS: Participants in the Medical Research Council (MRC)
      national survey of health and development, a population based birth cohort study
      established in 1946. MAIN OUTCOME MEASURES: Abdominal pain present throughout
      childhood in the absence of defined organic disease, and measures of physical
      symptoms and psychiatric disorder at age 36 years. RESULTS: There were high rates
      of complaints about physical health among the parents of children with persistent
      abdominal pain, and the mothers had higher neuroticism scores. Children with
      persistent abdominal pain were more likely to suffer from psychiatric disorders
      in adulthood (odds ratio 2.72 (95% confidence interval 1.65 to 4.49)) but were
      not especially prone to physical symptoms once psychiatric disorder was
      controlled for (odds ratio 1. 39 (0.83 to 2.36)). CONCLUSIONS: Persistent
      abdominal pain is associated with poor health and emotional disorder in the
      parents. Children with abdominal pain do not necessarily continue to experience
      physical symptoms into adulthood but are at increased risk of adult psychiatric
      disorders.

PMID- 9552996
TI  - Asherisms 

PMID- 9552995
TI  - Effect of electrical cardioversion on myocardial cells in patients in intensive
      care.

PMID- 9552997
TI  - Who's out there? 

PMID- 9552998
TI  - Screening for hypercholesterolaemia in primary care: randomised controlled trial
      of postal questionnaire appraising risk of coronary heart disease.
AB  - OBJECTIVES: To validate a self administered postal questionnaire appraising risk
      of coronary heart disease. To determine whether use of this questionnaire
      increased the percentage of people at high risk of coronary heart disease and
      decreased the percentage of people at low risk who had their cholesterol
      concentration measured. DESIGN: Validation was by review of medical records and
      clinical assessment. The questionnaire appraising risk of coronary heart disease
      encouraged those meeting criteria for cholesterol measurement to have a
      cholesterol test and was tested in a randomised controlled trial. The
      intervention group was sent the risk appraisal questionnaire with a health
      questionnaire that determined risk of coronary heart disease without identifying
      the risk factors as related to coronary heart disease; the control group was sent
      the health questionnaire alone. SETTING: One capitation funded primary care
      practice in Canada with an enrolled patient population of about 12 000. SUBJECTS:
      Random sample of 100 participants in the intervention and control groups were
      included in the validation exercise. 5686 contactable patients aged 20 to 69
      years who on the basis of practice records had not had a cholesterol test
      performed during the preceding 5 years were included in the randomised controlled
      trial. 2837 were in the intervention group and 2849 were in the control group.
      MAIN OUTCOME MEASURES: Sensitivity and specificity of assessment of risk of
      coronary heart disease with risk appraisal questionnaire. Rate of cholesterol
      testing during three months of follow up. RESULTS: Sensitivity of questionnaire
      appraising coronary risk was 87.5% (95% confidence interval 73.2% to 95.8%) and
      specificity 91.7% (81.6% to 97.2%). Of the patients without pre-existing coronary
      heart disease who met predefined screening criteria based on risk, 45 out of 421
      in the intervention group (10.7%) and 9 out of 504 in the control group (1.8%)
      had a cholesterol test performed during follow up (P<0.0001). Of the patients
      without a history of coronary heart disease who did not meet criteria for
      cholesterol testing, 30 out of 1128 in the intervention group (2.7%) and 18 out
      of 1099 in the control group (1.6%) had a cholesterol test (P=0.175). Of the
      patients with pre-existing coronary heart disease, 1 out of 15 in the
      intervention group (6.7%) and 1 out of 23 in the control group (4.3%) were tested
      during follow up (P=0.851, one tailed Fisher's exact test). CONCLUSIONS: Although
      the questionnaire appraising coronary risk increased the percentage of people at
      high risk who obtained cholesterol testing, the effect was small. Most patients
      at risk who received the questionnaire did not respond by having a test.

PMID- 9553000
TI  - The new NHS: medical students say no 

PMID- 9552999
TI  - Systematic review of dietary intervention trials to lower blood total cholesterol
      in free-living subjects.
AB  - OBJECTIVES: To estimate the efficacy of dietary advice to lower blood total
      cholesterol concentration in free-living subjects and to investigate the efficacy
      of different dietary recommendations. DESIGN: Systematic overview of 19
      randomised controlled trials including 28 comparisons. SUBJECTS: Free-living
      subjects. INTERVENTIONS: Individualised dietary advice to modify fat intake. MAIN
      OUTCOME MEASURE: Percentage difference in blood total cholesterol concentration
      between the intervention and control groups. RESULTS: The percentage reduction in
      blood total cholesterol attributable to dietary advice after at least six months
      of intervention was 5.3% (95% confidence interval 4.7% to 5.9%). Including both
      short and long duration studies, the effect was 8.5% at 3 months and 5.5% at 12
      months. Diets equivalent to the step 2 diet of the American Heart Association
      were of similar efficacy to diets that aimed to lower total fat intake or to
      raise the polyunsaturated to saturated fatty acid ratio. These diets were
      moderately more effective than the step 1 diet of the American Heart Association
      (6.1% v 3.0% reduction in blood total cholesterol concentration; P<0.0001). On
      the basis of reported food intake, the targets for dietary change were seldom
      achieved. The observed reductions in blood total cholesterol concentrations in
      the individual trials were consistent with those predicted from dietary intake on
      the basis of the Keys equation. CONCLUSIONS: Individualised dietary advice for
      reducing cholesterol concentration is modestly effective in free-living subjects.
      More intensive diets achieve a greater reduction in serum cholesterol
      concentration. Failure to comply fully with dietary recommendations is the likely
      explanation for this limited efficacy.

PMID- 9553002
TI  - A victorian polymath 

PMID- 9553003
TI  - Allergy and the skin. II--Contact and atopic eczema.

PMID- 9553001
TI  - Diabetes.

PMID- 9553005
TI  - I saved my father's life 

PMID- 9553004
TI  - North of England evidence based guidelines development project: methods of
      developing guidelines for efficient drug use in primary care.

PMID- 9553006
TI  - What's wrong with Bonferroni adjustments.

PMID- 9553007
TI  - The doctor's losses: ideals versus realities.

PMID- 9553008
TI  - Old remedy effective 

PMID- 9553009
TI  - Economic benefit analysis of primary prevention with pravastatin. Modelling
      economic benefits after such long term treatment is inappropriate.

PMID- 9553010
TI  - Day case surgery has benefited patients with cataract in North Gwent.

PMID- 9553011
TI  - Article about mental health law gave practical guidance.

PMID- 9553012
TI  - Risk language and dialects. Expressing risk in relative rather than absolute
      terms is important.

PMID- 9553013
TI  - Fate of special hospitals in england has not yet been decided 

PMID- 9553014
TI  - Sexual abuse is not the only childhood adversity that may lead to later
      depression.

PMID- 9553015
TI  - Training in plastic surgery is being set up in The Gambia.

PMID- 9553016
TI  - Management of Helicobacter pylori infection. Eradication treatment should be
      limited to patients with proved peptic ulceration.

PMID- 9553017
TI  - Patients with implants should be given implant cards. Intraocular lens implant
      cards contain inadequate clinical data.

PMID- 9553018
TI  - General practice must decide on its own education system.

PMID- 9553019
TI  - Regulation of body weight is social skill.

PMID- 9553020
TI  - Mouth care and skin care in palliative medicine. Chlorhexidine mouth washes are
      important in mouth care.

PMID- 9553021
TI  - Possible association between low birth weight and later heart disease needs to be
      investigated further.

PMID- 9553022
TI  - BMA must voice its opposition to Cuban embargo.

PMID- 9553023
TI  - Punishment of doctors must fit their crime.

PMID- 9553025
TI  - BMA's counselling service takes over 6000 calls 

PMID- 9553024
TI  - William louis murray bigby 

PMID- 9553027
TI  - Is rationing down under upside down? 

PMID- 9553026
TI  - Patients not paper? 

PMID- 9553028
TI  - Listen to the patient 

PMID- 9553030
TI  - Rationing: talk and action in health care 

PMID- 9553029
TI  - Genetics of common diseases 

PMID- 9553031
TI  - Early selegiline treatment in Parkinson's disease may not be advantageous 

PMID- 9553032
TI  - Abdominal pain in childhood is linked with psychiatric disorders in adulthood 

PMID- 9553033
TI  - Aminosidine is more effective than sodium stibogluconate in visceral
      leishmaniasis 

PMID- 9553034
TI  - Suicide risk is increased in stroke 

PMID- 9553035
TI  - Postal risk appraisal questionnaire slightly increases cholesterol testing in
      high risk patients 

PMID- 9553036
TI  - Individual dietary advice has modest effects on cholesterol 

PMID- 9553037
TI  - The telomerase reverse transcriptase: components and regulation.

PMID- 9553039
TI  - A specific, nonproliferative role for E2F-5 in choroid plexus function revealed
      by gene targeting.
AB  - Homozygous E2F-5 knockout embryos and mice have been generated. Although
      embryonic development appeared normal, newborn mice developed nonobstructive
      hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production.
      Although the CSF-producing choroid plexus displayed normal cellular organization,
      it contained abundant electron-lucent epithelial cells, consistent with excessive
      CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was
      largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in
      homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell
      proliferation. Rather, it affects the secretory behavior of a differentiated
      neural tissue.

PMID- 9553038
TI  - Delta and Serrate are redundant Notch ligands required for asymmetric cell
      divisions within the Drosophila sensory organ lineage.
AB  - Asymmetric divisions allow a precursor to produce four distinct cells of a
      Drosophila sensory organ lineage (SOL). Whereas this process requires cell-cell
      communication via Notch (N) receptor, mitotic recombination that removes the N
      ligand Delta (Dl) or Serrate (Ser) in the SOL had mild or no effect. Removal of
      both Dl and Ser, however, led to cell fate transformations similar to the N
      phenotype. Cell fate transformation occurred even when a single SOL cell lost
      both Dl and Ser. Thus, Dl and Ser are redundant in mediating signaling between
      daughter cells to specify their distinct cell fates.

PMID- 9553040
TI  - Cytokine rescue of p53-dependent apoptosis and cell cycle arrest is mediated by
      distinct Jak kinase signaling pathways.
AB  - Exposure of hematopoietic progenitors to gamma-irradiation (IR) induces p53
      dependent apoptosis and a p53-independent G2/M cell cycle arrest. These responses
      to DNA-damage can be inhibited by treatment with cytokine growth factors. Here we
      report that gamma-IR-induced apoptosis and cell cycle arrest are suppressed by
      specific cytokines (e.g., erythropoietin and interleukin-3) and that activation
      of the Jak kinase is necessary and sufficient for these effects. Using myleoid
      cells expressing a series of erythropoietin receptor (EpoR) mutants, we have
      demonstrated that Jak kinase-dependent signals initiated from the membrane
      proximal domain of EpoR were sufficient to prevent IR-induced apoptotic cell
      death, but failed to prevent cell cycle arrest. Cell survival by Epo did not
      require activation of other known signaling pathways including PI-3 kinase, PLC
      gamma, Ras or Stats. Signaling targets of Jak kinase pathways included members of
      the Bcl-2 family of anti-apoptotic proteins, and enforced expression of Bcl-2 or
      Bcl-xL was as effective as cytokine treatment in blocking IR-induced apoptosis
      but did not prevent growth arrest. A distinct signal derived from a membrane
      distal domain of EpoR is required to overcome growth arrest associated with DNA
      damage. These findings functionally link the Jak signaling pathway to suppression
      of p53-mediated cell death by cytokines and demonstrate that the apoptotic and
      growth arrest responses to DNA damage in hematopoietic cells are modulated by
      distinct, cytokine specific signal transduction pathways.

PMID- 9553041
TI  - Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires
      association with the inducible chaperone Hsp70.
AB  - The Wilms tumor suppressor WT1 encodes a zinc finger transcription factor that is
      expressed in glomerular podocytes during a narrow window in kidney development.
      By immunoprecipitation and protein microsequencing analysis, we have identified a
      major cellular protein associated with endogenous WT1 to be the inducible
      chaperone Hsp70. WT1 and Hsp70 are physically associated in embryonic rat kidney
      cells, in primary Wilms tumor specimens and in cultured cells with inducible
      expression of WT1. Colocalization of WT1 and Hsp70 is evident within podocytes of
      the developing kidney, and Hsp70 is recruited to the characteristic subnuclear
      clusters that contain WT1. The amino-terminal transactivation domain of WT1 is
      required for binding to Hsp70, and expression of that domain itself is sufficient
      to induce expression of Hsp70 through the heat shock element (HSE). Substitution
      of a heterologous Hsp70-binding domain derived from human DNAJ is sufficient to
      restore the functional properties of a WT1 protein with an amino-terminal
      deletion, an effect that is abrogated by a point mutation in DNAJ that reduces
      binding to Hsp70. These observations indicate that Hsp70 is an important cofactor
      for the function of WT1, and suggest a potential role for this chaperone during
      kidney differentiation.

PMID- 9553042
TI  - Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a
      range of highly metastatic tumors.
AB  - A role for the membrane/cytoskeleton interface in the development and progression
      of cancer is established, yet poorly understood. The neurofibromatosis type II
      (NF2) tumor suppressor gene encodes a member of the ezrin/radixin/moesin (ERM)
      family of membrane/cytoskeleton linker proteins thought to be important for cell
      adhesion and motility. We report that in contrast to the narrow spectrum of
      benign tumors in human NF2 patients, Nf2 heterozygous mice develop a variety of
      malignant tumors. Using the fact that Nf2 is linked to the p53 tumor suppressor
      locus in the mouse we have also investigated the effects of genetic linkage of
      cancer-predisposing mutations on tumorigenesis and examined the genetic pathway
      to tumor formation involving Nf2 loss. Importantly, we observed a very high rate
      of metastasis associated with Nf2 deficiency, with or without loss of p53
      function, and we provide experimental evidence supporting a role for Nf2 loss in
      metastatic potential. Together, our results suggest an important role for the NF2
      tumor suppressor, and perhaps the ERM family in tumor formation and metastasis.

PMID- 9553043
TI  - RecQ helicase, in concert with RecA and SSB proteins, initiates and disrupts DNA
      recombination.
AB  - RecQ helicase is important to homologous recombination and DNA repair in
      Escherichia coli. We demonstrate that RecQ helicase, in conjunction with RecA and
      SSB proteins, can initiate recombination events in vitro. In addition, RecQ
      protein is capable of unwinding a wide variety of DNA substrates, including joint
      molecules formed by RecA protein. These data are consistent with RecQ helicase
      assuming two roles in the cell; it can be (1) an initiator of homologous
      recombination, or (2) a disrupter of joint molecules formed by aberrant
      recombination. These findings also shed light on the function of the eukaryotic
      homologs of RecQ helicase, the Sgs1, Blm, and Wrn helicases.

PMID- 9553044
TI  - The control of maize spikelet meristem fate by the APETALA2-like gene
      indeterminate spikelet1.
AB  - The orderly production of meristems with specific fates is crucial for the proper
      elaboration of plant architecture. The maize inflorescence meristem branches
      several times to produce lateral meristems with determinate fates. The first
      meristem formed, the spikelet pair meristem, produces two spikelet meristems,
      each of which produces two floral meristems. We have identified a gene called
      indeterminate spikelet1 (ids1) that specifies a determinate spikelet meristem
      fate and thereby limits the number of floral meristems produced. In the absence
      of ids1 gene function, the spikelet meristem becomes indeterminate and produces
      additional florets. Members of the grass family vary in the number of florets
      within their spikelets, suggesting that ids1 may play a role in inflorescence
      architecture in other grass species. ids1 is a member of the APETALA2 (AP2) gene
      family of transcription factors that has been implicated in a wide range of plant
      development roles. Expression of ids1 was detected in many types of lateral organ
      primordia as well as spikelet meristems. Our analysis of the ids1 mutant
      phenotype and expression pattern indicates that ids1 specifies determinate fates
      by suppressing indeterminate growth within the spikelet meristem.

PMID- 9553045
TI  - DWnt-2, a Drosophila Wnt gene required for the development of the male
      reproductive tract, specifies a sexually dimorphic cell fate.
AB  - The sexually dimorphic characteristics of the reproductive tract in Drosophila
      require that cells of the gonad and the genital disc be assigned sex-specific
      fates. We report here that DWnt-2, a secreted glycoprotein related to wingless,
      is a signal required for cell fate determination and morphogenesis in the
      developing male reproductive tract. Testes from DWnt-2 null mutant flies lack the
      male-specific pigment cells of the reproductive tract sheath and the muscle
      precursors of the sheath fail to migrate normally. However, other cell types of
      the testis are unaffected. DWnt-2 is expressed in somatic cells of the gonad
      throughout development, implicating it as a signal that can influence pigment
      cell fate directly. Indeed, the ectopic expression of DWnt-2 in females results
      in the appearance of male-specific pigment cells in otherwise morphologically
      normal ovaries. Thus, the presence of pigment cells is a sexually dimorphic trait
      that is controlled by DWnt-2 expression. DWnt-2 is also expressed in regions of
      the male genital disc and gonad, which we have identified as sites of contact
      with muscle precursor cells, suggesting that secreted DWnt-2 protein is a signal
      for the migration or attachment of these cells.

PMID- 9553046
TI  - Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase
      signaling in oogenesis: cytoplasmic retention and degradation.
AB  - Dorsoventral (D/V) patterning in Drosophila oogenesis is initiated by the
      transmission of a TGF-alpha-like ligand, Gurken (Grk), from the oocyte to the
      anterodorsal follicle cells, activating the EGF receptor (Egfr) signaling
      pathway. The zinc-finger transcription factor CF2 is a negative regulator of the
      rhomboid (rho) gene that encodes an essential membrane-bound component of the
      dorsalizing pathway. Expression of CF2 itself is negatively regulated by the
      activated Egfr. In this report, we demonstrate that CF2 is the target of down
      regulation by the MAPK kinase cascade, and that this down-regulation is
      independent of the Rho function. These results suggest that D/V patterning
      involves a two-step signaling process: the initial Egfr signal, which represses
      CF2 and induces rho expression; and the subsequent Egfr + Rho signal, which
      determines the dorsal cell fates. Furthermore, we show that CF2 down-regulation
      occurs at the post-translational level through a mechanism involving coupled
      cytoplasmic retention and degradation.

PMID- 9553047
TI  - Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA
      1 transcriptional cofactor FOG.
AB  - GATA transcription factors are required for the differentiation of diverse cell
      types in several species. Recent evidence suggests that their biologic activities
      may be modulated through interaction with multitype zinc finger proteins, such as
      Friend of GATA-1 (FOG) and U-shaped (Ush). In cell culture, FOG cooperates with
      the hematopoietic transcription factor GATA-1 to promote erythroid and
      megakaryocytic differentiation. We show here that mice lacking FOG die during mid
      embryonic development with severe anemia. FOG-/- erythroid cells display a
      marked, but partial, blockage of maturation, reminiscent of GATA-1- erythroid
      precursors. In contrast to GATA-1 deficiency, however, megakaryocytes fail to
      develop in the absence of FOG. Although the FOG-/- erythroid phenotype supports
      the proposed role of FOG as a GATA-1 cofactor in vivo, the latter finding points
      to a pivotal, GATA-1-independent requirement for FOG in megakaryocyte development
      from the bipotential erythroid/megakaryocytic progenitor. We speculate that FOG
      and other FOG-like proteins serve as complex cofactors that act through both GATA
      dependent and GATA-independent mechanisms.

PMID- 9553048
TI  - Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice
      lacking the sterol carrier protein-2/sterol carrier protein-x gene function.
AB  - Gene targeting in mice was used to investigate the unknown function of Scp2,
      encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol
      carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal
      thiolase). Complete deficiency of SCP2 and SCPx was associated with marked
      alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired
      body weight control, and neuropathy. Along with these abnormalities, catabolism
      of methyl-branched fatty acyl CoAs was impaired. The defect became evident from
      up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid
      in Scp2(-/-) mice. Further characterization supported that the gene disruption
      led to inefficient import of phytanoyl-CoA into peroxisomes and to defective
      thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high
      affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as
      high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein.

PMID- 9553049
TI  - Knockout and knockin of the beta1 exon D define distinct roles for integrin
      splice variants in heart function and embryonic development.
AB  - The beta1D integrin is a recently characterized isoform of the beta1 subunit that
      is specifically expressed in heart and skeletal muscle. In this study we have
      assessed the function of the beta1D integrin splice variant in mice by
      generating, for the first time, Cre-mediated exon-specific knockout and knockin
      strains for this splice variant. We show that removal of the exon for beta1D
      leads to a mildly disturbed heart phenotype, whereas replacement of beta1A by
      beta1D results in embryonic lethality with a plethora of developmental defects,
      in part caused by the abnormal migration of neuroepithelial cells. Our data
      demonstrate that the splice variants A and D are not functionally equivalent. We
      propose that beta1D is less efficient than beta1A in mediating the signaling that
      regulates cell motility and responses of the cells to mechanical stress.

PMID- 9553052
TI  - Complex, two-way traffic of molecules across the membrane of the endoplasmic
      reticulum.

PMID- 9553050
TI  - pX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250
      mutants.
AB  - Hepatitis B virus (HBV) infects humans and causes a wide range of clinical
      manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV
      genome contains multiple promoters with gene expression regulated predominantly
      by the cellular transcription initiation machinery. Accordingly, the HBV-encoded
      pX, the only known viral regulator, is a potent transcription coactivator. We
      investigated the relationship between pX and cellular coactivators. We show that
      pX restores wild-type activity to inactive TBPAS mutants with poor TAFII250 and
      activator-binding activity. This pX-mediated recovery, however, is not obtained
      with inactive TBPAS mutants in binding of other general transcription factors.
      Remarkably, ts13, a cell line temperature sensitive for TAFII250 function,
      exhibiting growth arrest and apoptosis at the restrictive temperature, is rescued
      partially by pX expression, thus generating a pX-dependent cell growth.
      Collectively, our results suggest that pX suppresses some of the phenotypes of
      TBP and TAFII250 mutations, implying that pX circumvents the need for a holo
      TFIID complex for transcription activation to proceed.

PMID- 9553053
TI  - Catalytic domain of the p120 Ras GAP binds to RAb5 and stimulates its GTPase
      activity.
AB  - Ras is a master GTPase switch controlling multiple signal transduction cascades
      in the regulation of cell proliferation and differentiation. Rab5 is a local
      GTPase switch that is localized on early endosomes and controls early endosome
      fusion. This study demonstrates that the catalytic domain of p120 GTPase
      activating protein (GAP), a well known Ras GAP, is able to interact physically
      with Rab5 and stimulate its GTPase activity. This GAP activity toward Rab5,
      however, cannot be extended to other Rab GTPases such as Rab3, Rab4, and Rab6,
      indicating that it is not a generic GAP for the Rab family of GTPases that
      regulate intracellular membrane fusion during endocytosis and exocytosis. The
      findings indicate a level of structural similarity between Ras and Rab5
      unexpected from their primary sequences. They also suggest a possible signal
      transduction regulation of the Rab5-dependent endosome fusion via the Ras GAP.

PMID- 9553051
TI  - Autocrine growth and anchorage independence: two complementing Jun-controlled
      genetic programs of cellular transformation.
AB  - Cellular transformation can be achieved by constitutive activation of growth
      regulatory signaling pathways, which, in turn, activate nuclear transcription
      factors thought to execute a transformation-specific program of gene expression.
      Members of the dimeric transcription factor family AP-1 are at the receiving end
      of such growth-regulating pathways and the viral form of the AP-1 subunit Jun
      establishes one important aspect of transformation in chick embryo fibroblasts
      (CEFs): enhanced growth in agar and in low serum. Enhanced Jun activity is likely
      to target several different genetic programs as Jun forms heterodimers with one
      of several members of the Fos and ATF2 subfamilies, resulting in transcription
      factors with different sequence specificities. To identify the programs relevant
      for transformation, we have reduced the complexity of AP-1 factors by
      constructing Jun bZip mutants that can efficiently dimerize and transactivate
      with only a restricted set of partner subunits. Upon introduction into CEFs, a
      Jun mutant selective for the Fos family induced anchorage-independent growth but
      no growth factor-independence. In contrast, a c-Jun mutant with preference for
      ATF2-like proteins caused growth factor-independence, but no growth in agar.
      Coexpression of both mutants reestablished the combined transformation program as
      induced by wild-type Jun. These data show that Jun-dependent cell transformation
      can be resolved into at least two distinct and independent processes, anchorage
      and growth factor independence, obviously triggered by two classes of Jun
      heterodimers likely regulating different sets of target genes.

PMID- 9553054
TI  - ATP binding induces large conformational changes in the apical and equatorial
      domains of the eukaryotic chaperonin containing TCP-1 complex.
AB  - The chaperonin-containing TCP-1 complex (CCT) is a heteromeric particle composed
      of eight different subunits arranged in two back-to-back 8-fold pseudo-symmetric
      rings. The structural and functional implications of nucleotide binding to the
      CCT complex was addressed by electron microscopy and image processing. Whereas
      ADP binding to CCT does not reveal major conformational differences when compared
      with nucleotide-free CCT, ATP binding induces large conformational changes in the
      apical and equatorial domains, shifting the latter domains up to 40 degrees (with
      respect to the inter-ring plane) compared with 10 degrees for nucleotide-free CCT
      or ADP-CCT. This equatorial ATP-induced shift has no counterpart in GroEL, its
      prokaryotic homologue, which suggests differences in the folding mechanism for
      CCT.

PMID- 9553055
TI  - Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits
      interleukin-8-induced neutrophil migration.
AB  - Interleukin-8 (IL-8) and closely related Glu-Leu-Arg (ELR) containing CXC
      chemokines, including growth-related oncogene (GRO)alpha, GRObeta, GROgamma, and
      epithelial cell-derived neutrophil-activating peptide-78 (ENA-78), are potent
      neutrophil chemotactic and activating peptides, which are proposed to be major
      mediators of inflammation. IL-8 activates neutrophils by binding to two distinct
      seven-transmembrane (7-TMR) G-protein coupled receptors CXCR1 (IL-8RA) and CXCR2
      (IL-8RB), while GROalpha, GRObeta, GROgamma, and ENA-78 bind to and activate only
      CXCR2. A chemical lead, which selectively inhibited CXCR2 was discovered by high
      throughput screening and chemically optimized. SB 225002 (N-(2-hydroxy-4
      nitrophenyl)-N'-(2-bromophenyl)urea) is the first reported potent and selective
      non-peptide inhibitor of a chemokine receptor. It is an antagonist of 125I-IL-8
      binding to CXCR2 with an IC50 = 22 nM. SB 225002 showed >150-fold selectivity
      over CXCR1 and four other 7-TMRs tested. In vitro, SB 225002 potently inhibited
      human and rabbit neutrophil chemotaxis induced by both IL-8 and GROalpha. In
      vivo, SB 225002 selectively blocked IL-8-induced neutrophil margination in
      rabbits. The present findings suggest that CXCR2 is responsible for neutrophil
      chemotaxis and margination induced by IL-8. This selective antagonist will be a
      useful tool compound to define the role of CXCR2 in inflammatory diseases where
      neutrophils play a major role.

PMID- 9553056
TI  - Requirement for Rho-mediated myosin light chain phosphorylation in thrombin
      stimulated cell rounding and its dissociation from mitogenesis.
AB  - Thrombin treatment causes a dose-dependent rounding of 1321N1 astrocytoma cells.
      This cytoskeletal response is rapid, peaking 2 h after thrombin stimulation, and
      reverses by 50% after 24 h. The thrombin receptor peptide SFLLRNP also induces
      cell rounding, whereas other G protein-linked receptor agonists such as
      carbachol, lysophosphatidic acid, or bradykinin fail to do so. Results of studies
      using pharmacological inhibitors do not support a requirement for
      phosphatidylinositol 3-kinase, mitogen-activated protein kinase, or Ca2+
      mobilization in this response. Inhibition of protein kinase C or tyrosine kinase
      produces minimal blockade. Pertussis toxin treatment is also without effect.
      However, thrombin-induced rounding is fully blocked by the C3 toxin from
      Clostridium botulinum, which specifically ADP-ribosylates and inactivates the
      small G protein Rho. Thrombin also leads to a rapid, 2.4-fold increase in 32P
      incorporation into myosin light chain while carbachol does not. Myosin
      phosphorylation, like cell rounding is inhibited by inactivation of Rho with C3
      exoenzyme, suggesting that myosin phosphorylation is necessary for this
      cytoskeletal response. This is supported by the observation that thrombin-induced
      rounding is also blocked by the myosin light chain kinase inhibitor KT5926.
      However, treatment with KT5926 fails to inhibit mitogenesis. Thus, cell rounding
      is not prerequisite to thrombin-induced DNA synthesis. We conclude that
      stimulation of the heterotrimeric G protein-coupled thrombin receptor in 1321N1
      cells activates Rho-dependent pathways for both DNA synthesis and cell rounding,
      the cytoskeletal response being mediated in part through increases in myosin
      phosphorylation.

PMID- 9553057
TI  - Generation of constitutively active recombinant caspases-3 and -6 by
      rearrangement of their subunits.
AB  - Caspases play a major role in the transduction of the apoptotic signal and
      execution of apoptosis in mammalian cells. Ectopic overexpression of the short
      prodomain caspases-3 and -6 precursors in mammalian cells does not induce
      apoptosis. This is due to their inability to undergo autocatalytic
      processing/activation and suggests that they depend on the long prodomain
      caspases for activation. To investigate directly the apoptotic activity of these
      two caspases in vivo, we engineered constitutively active recombinant caspases-3
      and -6 precursors. This was achieved by making contiguous precursor caspases-3
      and -6 molecules, which have their small subunits preceding their large subunits.
      Unlike their wild type counterparts, these recombinant molecules were capable of
      autocatalytic processing in an in vitro translation reaction, suggesting that
      they are catalytically active. They were also capable of autoprocessing and
      inducing apoptosis in vivo independent of the upstream caspases. Furthermore,
      their autocatalytic and apoptotic activities were inhibited by the pancaspase
      inhibitor z-VAD-fluoromethylketone, but not by CrmA or Bcl-2, thus directly
      demonstrating that the targets of inhibition of apoptosis by CrmA and Bcl-2 are
      upstream of caspases-3 and -6. Since caspases-3 and -6 are the most downstream
      executioners of apoptosis, the constitutively active versions of these caspases
      could be used at very low concentrations in gene therapy model systems to induce
      apoptosis in target tissues or tumors.

PMID- 9553058
TI  - The GABP-responsive element of the interleukin-2 enhancer is regulated by
      JNK/SAPK-activating pathways in T lymphocytes.
AB  - T cell activation leads via multiple intracellular signaling pathways to rapid
      induction of interleukin-2 (IL-2) expression, which can be mimicked by
      costimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) and ionomycin. We
      have identified a distal IL-2 enhancer regulated by the Raf-MEK-ERK signaling
      pathway, which can be induced by TPA/ionomycin treatment. It contains a dyad
      symmetry element (DSE) controlled by the Ets-like transcription factor GA-binding
      protein (GABP), a target of activated ERK. TPA/ionomycin treatment of T cells
      stimulates both mitogen-activated ERK, as well as the stress-activated mitogen
      activated protein kinase family members JNK/SAPK and p38. In this study, we
      investigated the contribution of the stress-activated pathways to the induction
      of the distal IL-2 enhancer. We show that JNK- but not p38-activating pathways
      regulate the DSE activity. Furthermore, the JNK/SAPK signaling pathway cooperates
      with the Raf-MEK-ERK cascade in TPA/ionomycin-induced DSE activity. In T cells,
      overexpression of SPRK/MLK3, an activator of JNK/SAPK, strongly induces DSE
      dependent transcription and dominant negative kinases of SEK and SAPK impair
      TPA/ionomycin-induced DSE activity. Blocking both ERK and JNK/SAPK pathways
      abolishes the DSE induction. The inducibility of the DSE is strongly dependent on
      the Ets-core motifs, which are bound by GABP. Both subunits of GABP are
      phosphorylated upon JNK activation in vivo and three different isoforms of
      JNK/SAPK, but not p38, in vitro. Our data suggest that GABP is targeted by
      signaling events from both ERK and JNK/SAPK pathways. GABP therefore is a
      candidate for signal integration and regulation of IL-2 transcription in T
      lymphocytes.

PMID- 9553059
TI  - Sugar response sequence in the promoter of a rice alpha-amylase gene serves as a
      transcriptional enhancer.
AB  - Expression of alpha-amylase genes in both rice suspension cells and germinating
      embryos is repressed by sugars and the mechanism involves transcriptional
      regulation. The promoter of a rice alpha-amylase gene alphaAmy3 was analyzed by
      both loss- and gain-of-function studies and the major sugar response sequence
      (SRS) was located between 186 and 82 base pairs upstream of the transcription
      start site. The SRS conferred sugar responsiveness to a minimal promoter in an
      orientation-independent manner. It also converted a sugar-insensitive rice actin
      gene promoter into a sugar-sensitive promoter in a dose-dependent manner. Linker
      scan mutation studies identified three essential motifs: the GC box, the G box,
      and the TATCCA element, within the SRS. Sequences containing either the GC box
      plus G box or the TATCCA element each mediated sugar response, however, they
      acted synergistically to give a high level glucose starvation-induced expression.
      Nuclear proteins from rice suspension cells binding to the TATCCA element in a
      sequence-specific and sugar-dependent manner were identified. The TATCCA element
      is also an important component of the gibberellin response complex of the alpha
      amylase genes in germinating cereal grains, suggesting that the regulation of
      alpha-amylase gene expression by sugar and hormone signals may share common
      regulatory machinery.

PMID- 9553060
TI  - Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1.
      Cooperation of the nucleotide binding domains.
AB  - The human multidrug transporter (MDR1 or P-glycoprotein) is an ATP-dependent
      cellular drug extrusion pump, and its function involves a drug-stimulated,
      vanadate-inhibited ATPase activity. In the presence of vanadate and MgATP, a
      nucleotide (ADP) is trapped in MDR1, which alters the drug binding properties of
      the protein. Here, we demonstrate that the rate of vanadate-dependent nucleotide
      trapping by MDR1 is significantly stimulated by the transported drug substrates
      in a concentration-dependent manner closely resembling the drug stimulation of
      MDR1-ATPase. Non-MDR1 substrates do not modulate, whereas N-ethylmaleimide, a
      covalent inhibitor of the ATPase activity, eliminates vanadate-dependent
      nucleotide trapping. A deletion in MDR1 (Delta amino acids 78-97), which alters
      the substrate stimulation of its ATPase activity, similarly alters the drug
      dependence of nucleotide trapping. MDR1 variants with mutations of key lysine
      residues to methionines in the N-terminal or C-terminal nucleotide binding
      domains (K433M, K1076M, and K433M/K1076M), which bind but do not hydrolyze ATP,
      do not show nucleotide trapping either with or without the transported drug
      substrates. These data indicate that vanadate-dependent nucleotide trapping
      reflects a drug-stimulated partial reaction of ATP hydrolysis by MDR1, which
      involves the cooperation of the two nucleotide binding domains. The analysis of
      this drug-dependent partial reaction may significantly help to characterize the
      substrate recognition and the ATP-dependent transport mechanism of the MDR1 pump
      protein.

PMID- 9553061
TI  - Localization of the active site of HIV-1 reverse transcriptase-associated RNase H
      domain on a DNA template using site-specific generated hydroxyl radicals.
AB  - Reverse transcriptase (RT)-associated ribonuclease H (RNase H) can cleave both
      the RNA template of DNA/RNA hybrids as well as double-stranded (ds) RNA. This
      report shows that human immunodeficiency virus (HIV)-RT can also cleave the
      template strand of dsDNA when Mg2+ is replaced by Fe2+ in the RNase H active site
      of HIV-RT. The cleavage mechanisms as well as the positions of the cut vary
      depending on whether RNA or DNA is used. While DNA is cleaved 17 base positions
      upstream of the primer 3'-end, RNA is cleaved 18 base positions upstream.
      Competition experiments show that Fe2+ replaces the catalytically active Mg2+ of
      RT-associated RNase H. The bound Fe2+ is the source of locally generated OH
      radicals that cleave the most proximate base in the DNA. Electrophoretic mobility
      studies of the cleaved fragments suggest that DNA is cleaved by an oxidative
      mechanism, while RNA is cleaved by an enzymatic mechanism which is
      indistinguishable from the Mg2+-dependent cleavage. The Fe2+-dependent cuts can
      be used to trace the active site of RT-associated RNase H on dsDNA as well as on
      dsRNA and DNA/RNA hybrids. The observed 1 base difference in the cleavage
      positions on DNA and RNA templates can be attributed to conformational
      differences of the bound nucleic acids. We suggest that the lower pitch of dsRNA
      and DNA/RNA hybrids compared with dsDNA permits accommodation of an additional
      base pair in the region between the primer 3'-end and the Fe2+-dependent cleavage
      position at the RNase H active site.

PMID- 9553062
TI  - Prothymosin alpha stimulates Ca2+-dependent phosphorylation of elongation factor
      2 in cellular extracts.
AB  - Prothymosin alpha (PTA) stimulates in a dose-dependent manner the phosphorylation
      of a 105-kDa protein (p105) in cell extracts from different cell types. Protein
      sequencing and immunological analysis indicated that this protein is elongation
      factor 2 (EF-2). We propose that calcium/calmodulin-dependent protein kinase III
      is responsible for the PTA-dependent EF-2 phosphorylation based on the following
      lines of evidence: (a) Ca2+ is required for the effect; (b) calmodulin enhances
      the reaction, and calmodulin inhibitors block the phosphorylation; and (c) no
      phosphorylation is seen in cell extracts depleted of calmodulin-binding proteins.
      To obtain a strong phosphorylated EF-2 band, we found it necessary to add PTA to
      cytosolic extracts from synchronized dividing cells in various phases of the cell
      cycle except in mitosis. Since PTA is a nuclear protein everywhere in the cell
      cycle except in mitosis, when it is found in the cytoplasm, we hypothesize that,
      if PTA activates EF-2 phosphorylation in vivo, as present data suggest, its
      presence in the cytoplasm during mitosis could explain why EF-2 phosphorylation
      is mainly restricted to that phase of the cell cycle. Moreover, other bands in
      addition to EF-2 were phosphorylated in a calmodulin- and PTA-dependent manner,
      and several of them (in a range between 50 and 60 kDa) have similar Mr to those
      that conform to the holoenzyme calcium/calmodulin dependent protein kinase II,
      suggesting that PTA could have a more general function modulating the activity of
      various Ca2+/CaM-dependent enzymes along the cell cycle.

PMID- 9553063
TI  - The crk3 gene of Leishmania mexicana encodes a stage-regulated cdc2-related
      histone H1 kinase that associates with p12.
AB  - A cdc2-related protein kinase gene, crk3, has been isolated from the parasitic
      protozoan Leishmania mexicana. Data presented here suggests that crk3 is a good
      candidate to be the leishmanial cdc2 homologue but that the parasite protein has
      some characteristics which distinguish it from mammalian cdc2. crk3 is predicted
      to encode a 35.6-kDa protein with 54% sequence identity with the human cyclin
      dependent kinase cdc2 and 78% identity with the Trypanosoma brucei CRK3. The
      trypanosomatid CRK3 proteins have an unusual, poorly conserved 19-amino acid N
      terminal extension not present in human cdc2. crk3 is single copy, and there is 5
      fold higher mRNA in the replicative promastigote life-cycle stage than in the non
      dividing metacyclic form or mammalian amastigote form. A leishmanial suc-binding
      cdc2-related kinase (SBCRK) histone H1 kinase, has previously been described
      which binds the yeast protein, p13(suc1), and that has stage-regulated activity
      (Mottram J. C., Kinnaird, J., Shiels, B. R., Tait, A., and Barry, J. D. (1993) J.
      Biol. Chem. 268, 21044-21051). CRK3 from cell extracts of the three life-cycle
      stages was found to bind p13(suc1) and the leishmanial homologue p12(cks1). CRK3
      fused with six histidines at the C terminus was expressed in L. mexicana and
      shown to have SBCRK histone H1 kinase activity. Depletion of histidine-tagged
      CRK3 from L. mexicana cell extracts, by Ni-nitrilotriacetic acid agarose
      selection, reduced histone H1 kinase activity binding to p13(suc1). These data
      imply that crk3 encodes the kinase subunit of SBCRK. SBCRK and histidine-tagged
      CRK3 activities were inhibited by the purine analogue olomoucine with an IC50 of
      28 and 42 microM, respectively, 5-6-fold higher than human p34(cdc2)/cyclinB.

PMID- 9553064
TI  - Heparinase II from Flavobacterium heparinum. Role of histidine residues in
      enzymatic activity as probed by chemical modification and site-directed
      mutagenesis.
AB  - The three heparinases derived from Flavobacterium heparinum are powerful tools
      for studying heparin-like glycosaminoglycans in major biological processes,
      including angiogenesis and development. Heparinase II is unique among the three
      enzymes because it is able to catalytically cleave both heparin and heparan
      sulfate-like regions of heparin-like glycosaminoglycans. Toward understanding the
      catalytic mechanism of heparin-like glycosaminoglycan degradation by heparinase
      II, we set out to investigate the role of the histidines of heparinase II in
      catalysis. We observe concentration-dependent inactivation of heparinase II in
      the presence of the reversible histidine-modifying reagent diethylpyrocarbonate
      (DEPC). With heparin as the substrate, the rate constant of inactivation was
      found to be 0.16 min-1 mM-1; with heparan sulfate as the substrate, the rate
      constant was determined to be 0.24 min-1 mM-1. Heparinase II activity is restored
      following hydroxylamine treatment. This, along with other experiments, strongly
      suggests that the inactivation of heparinase II by DEPC is specific for histidine
      residues and that three histidines are modified by DEPC. Substrate protection
      experiments show that heparinase II preincubation with heparin followed by the
      addition of DEPC resulted in a loss of enzymatic activity toward heparan sulfate
      but not heparin. However, heparinase II preincubation with heparan sulfate was
      unable to protect heparinase II from DEPC inactivation for either of the
      substrates. Proteolytic mapping studies with Lys-C were consistent with the
      chemical modification experiments and identified histidines 238, 451, and 579 as
      being important for heparinase II activity. Further mapping studies identified
      histidine 451 as being essential for heparin degradation. Site-directed
      mutagenesis experiments on the 13 histidines of heparinase II corroborated the
      chemical modification and the peptide mapping studies, establishing the
      importance of histidines 238, 451 and 579 in heparinase II activity.

PMID- 9553065
TI  - Type I protein C deficiency caused by disruption of a hepatocyte nuclear factor
      (HNF)-6/HNF-1 binding site in the human protein C gene promoter.
AB  - Protein C is a vitamin K-dependent zymogen of a serine protease that inhibits
      blood coagulation by proteolytic inactivation of factors Va and VIIIa.
      Individuals affected by protein C deficiency are at risk for venous thrombosis.
      One such affected individual was shown earlier to carry a -14 T --> C mutation in
      the promoter region of the protein C gene. It is shown here that the region
      around this mutation corresponds to a binding site for the transcription factor
      hepatocyte nuclear factor (HNF)-6 and that this site completely overlaps an HNF-1
      binding site. HNF-6 and HNF-1 bound in a mutually exclusive manner. The -14 T -->
      C mutation reduced HNF-6 binding. In transient transfection experiments, HNF-6
      transactivated the wild-type protein C promoter and introduction of the mutation
      abolished transactivation by HNF-6. Similar experiments showed that wild-type
      protein C promoter activity was reduced by cotransfection of an HNF-1 expression
      vector. This inhibiting effect of HNF-1 was reversed to a stimulatory effect when
      promoter sequences either upstream or downstream of the HNF-6/HNF-1 site were
      deleted. It is concluded that HNF-6 is a major determinant of protein C gene
      activity. Moreover, this is the first report describing the putative involvement
      of HNF-6 and of an HNF-6 binding site in human pathology.

PMID- 9553066
TI  - Electron partitioning between the two branching quinol-oxidizing pathways in
      Acanthamoeba castellanii mitochondria during steady-state state 3 respiration.
AB  - Amoeba mitochondria possess a respiratory chain with two quinol-oxidizing
      pathways: the cytochrome pathway and the cyanide-resistant alternative oxidase
      pathway. The ADP/O method, based on the non-phosphorylating property of
      alternative oxidase, was used to determine contributions of both pathways in
      overall state 3 respiration in the presence of GMP (an activator of the
      alternative oxidase in amoeba) and succinate as oxidizable substrate. This method
      involves pair measurements of ADP/O ratios plus and minus benzohydroxamate (an
      inhibitor of the alternative oxidase). The requirements of the method are listed
      and verified. When overall state 3 respiration was decreased by increasing
      concentrations of n-butyl malonate (a non-penetrating inhibitor of succinate
      uptake), the quinone reduction level declined. At the same time, the alternative
      pathway contribution decreased sharply and became negligible when quinone redox
      state was lower than 50%, whereas the cytochrome pathway contribution first
      increased and then passed through a maximum at a quinone redox state of 58% and
      sharply decreased at a lower level of quinone reduction. This study is the first
      attempt to examine the steady-state kinetics of the two quinol-oxidizing pathways
      when both are active and to describe electron partitioning between them when the
      steady-state rate of the quinone-reducing pathway is varied.

PMID- 9553067
TI  - Events in the kinetic folding pathway of a small, all beta-sheet protein.
AB  - The folding of cardiotoxin analogue III (CTX III), a small (60 amino acids), all
      beta-sheet protein from the venom of the Taiwan Cobra (Naja naja atra) is here
      investigated. The folding kinetics is monitored by using a variety of techniques
      such as NMR, fluorescence, and circular dichroism spectroscopy. The folding of
      the protein is complete within a time scale of 200 ms. The earliest detectable
      event in the folding pathway of CTX III is the formation of a hydrophobic
      cluster, which possess strong affinity to bind to nonpolar dye such as 1-anilino
      8-napthalene-sulfonic acid. Quenched-flow deuterium-hydrogen exchange experiments
      indicate that the segment spanning residues 51-55 along with Lys23, Ile39, Val49,
      Tyr51 and Val52 could constitute the "hydrophobic cluster." Folding kinetics of
      CTX III based on the amide-protection data reveals that the triple-stranded,
      antiparallel beta-sheet segment, which is located in the central core of the
      molecule, appears to fold faster than the double-stranded beta-sheet segment.

PMID- 9553068
TI  - Transport and metabolism of the essential vitamin pantothenic acid in human
      erythrocytes infected with the malaria parasite Plasmodium falciparum.
AB  - The growth of the human malaria parasite, Plasmodium falciparum, within its host
      erythrocyte is reliant on the uptake of a number of essential nutrients from the
      extracellular medium. One of these is pantothenic acid, a water-soluble vitamin
      that is a precursor of coenzyme A. In this study we show that normal uninfected
      erythrocytes are impermeable to pantothenate but that the vitamin is taken up
      rapidly into malaria-infected cells via a transport pathway that has the
      characteristics (furosemide sensitivity, nonsaturability) of previously
      characterized, broad specificity permeation pathways induced by the intracellular
      parasite in the host cell membrane. The transport of pantothenate therefore
      constitutes a critical physiological role for these pathways. Inside the
      parasitized cell pantothenate undergoes phosphorylation, the first step in its
      conversion to coenzyme A. Parasites within saponin-permeabilized erythrocytes
      were shown to take up and phosphorylate pantothenate, consistent with the
      intracellular parasite having both a pantothenate transporter and a pantothenate
      kinase. Comparisons of the rate of phosphorylation of pantothenate by lysates
      prepared from uninfected and infected erythrocytes revealed that the pantothenate
      kinase activity of the P. falciparum trophozoite is some 10-fold higher than that
      of its host cell and that most, if not all, of the phosphorylation of
      pantothenate within the malaria-infected cell occurs within the intracellular
      parasite. These results contrast with those of previous studies in which it was
      proposed that the avian malaria parasite Plasmodium lophurae lacks pantothenate
      kinase (as well as the other enzymes for the synthesis of coenzyme A) and is
      reliant upon the uptake of preformed coenzyme A from the host cell cytosol.

PMID- 9553069
TI  - Human tyrosine hydroxylase isoforms. Inhibition by excess tetrahydropterin and
      unusual behavior of isoform 3 after camp-dependent protein kinase
      phosphorylation.
AB  - Human tyrosine hydroxylase exists as four isoforms (hTH1-4), generated by
      alternative splicing of pre-mRNA, with tissue-specific distribution.
      Unphosphorylated hTH3 and hTH1 were produced in large amounts in Escherichia coli
      and purified to homogeneity. The phosphorylation sites were determined after
      labeling with [32P]phosphate in the presence of cAMP-dependent protein kinase
      (PKA) and calmodulin-dependent protein kinase II (CaM-PKII). Ser40 was
      phosphorylated by PKA, and both Ser19 and Ser40 were phosphorylated by CaM-PKII.
      The enzyme kinetics of hTH3 were determined in the presence of various
      concentrations of the natural co-substrate (6R)-tetrahydrobiopterin and compared
      with those of recombinant hTH1 (similar to rat TH). We show that, under initial
      velocity conditions, excess (6R)-tetrahydrobiopterin inhibits hTH3 and hTH1. The
      TH catalytic constants (kcat) were determined for each of the two isoenzymes:
      hTH3 is about five times more active than hTH1. Phosphorylation by CaM-PKII did
      not affect the kinetic parameters of hTH3. The classical activation of TH by PKA
      phosphorylation, demonstrated for hTH1, was not observed with hTH3. Furthermore,
      hTH3 escapes activity regulation by phosphorylation and is always more active
      than phosphorylated hTH1. The properties of the hTH3 enzyme may be relevant to
      diseases affecting dopaminergic cells.

PMID- 9553070
TI  - Multiple regulatory elements in the 5'-flanking sequence of the human epsilon
      globin gene.
AB  - We have previously reported, on the basis of transfection experiments, the
      existence of a silencer element in the 5'-flanking region of the human embryonic
      (epsilon) globin gene, located at -270 base pairs 5' to the cap site, which
      provides negative regulation for this gene. Experiments in transgenic mice
      suggest the physiological importance of this epsilon-globin silencer, but also
      suggest that down-regulation of epsilon-globin gene expression may involve other
      negative elements flanking the epsilon-globin gene. We have now extended the
      analysis of epsilon-globin gene regulation to include the flanking region
      spanning up to 6 kilobase pairs 5' to the locus control region using reporter
      gene constructs with deletion mutations and transient transfection assays. We
      have identified and characterized other strong negative regulatory regions, as
      well as several positive regions that affect transcription activation. The
      negative regulatory regions at -3 kilobase pairs (epsilonNRA-I and epsilonNRA
      II), flanked by a positive control element, has a strong effect on the epsilon
      globin promoter both in erythroid K562 and nonerythroid HeLa cells and contains
      several binding sites for transcription factor GATA-1, as evidenced from DNA
      protein binding assays. The GATA-1 sites within epsilonNRA-II are directly needed
      for negative control. Both epsilonNRA-I and epsilonNRA-II are active on a
      heterologous promoter and hence appear to act as transcription silencers. Another
      negative control region located at -1.7 kilobase pairs (epsilonNRB) does not
      exhibit general silencer activity as epsilonNRB does not affect transcription
      activity when used in conjunction with an epsilon-globin minimal promoter. The
      negative effect of epsilonNRB is erythroid specific, but not stage-specific as it
      can repress transcription activity in both K562 erythroid cells as well as in
      primary cultures of adult erythroid cells. Phylogenetic DNA sequence comparisons
      with other primate and other mammalian species show unusual degree of flanking
      sequence homology for the epsilon-globin gene, including in several of the
      regions identified in these functional and DNA-protein binding analyses,
      providing alternate evidence for their potential importance. We suggest that the
      down-regulation of epsilon-globin gene expression as development progresses
      involves complex, cooperative interactions of these negative regulatory elements,
      epsilonNRA-I/epsilonNRA-II, epsilonNRB, the epsilon-globin silencer and probably
      other negative and positive elements in the 5'-flanking region of the epsilon
      globin gene.

PMID- 9553071
TI  - Selective inhibition of Ras interaction with its particular effector by synthetic
      peptides corresponding to the Ras effector region.
AB  - Ras proteins possess multiple downstream effectors of distinct structures. We and
      others demonstrated that Ha-Ras carrying certain effector region mutations could
      interact differentially with its effectors, implying that significant differences
      exist in their Ras recognition mechanisms. Here, by employing the fluorescence
      polarization method, we measured the activity of effector region synthetic
      peptides bearing various amino acid substitutions to inhibit association of Ras
      with the effectors human Raf-1 and Schizosaccharomyces pombe Byr2. The effect of
      these peptides on association with another effector Saccharomyces cerevisiae
      adenylyl cyclase was also examined by measuring inhibition of the Ras-dependent
      adenylyl cyclase activity. The peptide corresponding to the residues 17-44
      competitively inhibited Ras association with all the three effectors at the Ki
      values of 1 approximately 10 microM, and the inhibition was considerably
      attenuated by the D38A mutation. The peptide with the D38N mutation inhibited
      association of Ha-Ras with Byr2 but not with the others, whereas that with the
      P34G mutation inhibited association of Ha-Ras with Raf-1 and Byr2 but not with
      adenylyl cyclase. Thus, the specificity observed with the whole Ras protein was
      retained in the effector region peptide. These results suggest that the effector
      region residues constitute a major determinant for differential recognition of
      the effector molecules, raising a possibility for selective inhibition of a
      particular Ras function.

PMID- 9553072
TI  - Inhibition of assembly of bacterial cell division protein FtsZ by the hydrophobic
      dye 5,5'-bis-(8-anilino-1-naphthalenesulfonate).
AB  - To gain further insight into the structural relatedness of tubulin and FtsZ, the
      tubulin-like prokaryotic cell division protein, we tested the effect of tubulin
      assembly inhibitors on FtsZ assembly. Common tubulin inhibitors, such as
      colchicine, colcemid, benomyl, and vinblastine, had no effect on Ca2+-promoted
      GTP-dependent assembly of FtsZ into polymers. However, the hydrophobic probe 5,
      5'-bis-(8-anilino-1-naphthalenesulfonate) (bis-ANS) inhibited FtsZ assembly. The
      potential mechanisms for inhibition are discussed. Titrations of FtsZ with bis
      ANS indicated that FtsZ has one high affinity binding site and multiple low
      affinity binding sites. ANS (8-anilino-1-naphthalenesulfonate), a hydrophobic
      probe similar to bis-ANS, had no inhibitory effect on FtsZ assembly. Because
      tubulin assembly has also been shown to be inhibited by bis-ANS but not by ANS,
      it supports the idea that FtsZ and tubulin share similar conformational
      properties. Ca2+, which promotes GTP-dependent FtsZ assembly, stimulated binding
      of bis-ANS or ANS to FtsZ, suggesting that Ca2+ binding induces changes in the
      hydrophobic conformation of the protein. Interestingly, depletion of bound Ca2+
      with EGTA further enhanced bis-ANS fluorescence. These findings suggest that both
      binding and dissociation of Ca2+ are capable of inducing FtsZ conformational
      changes, and these changes could promote the GTP-dependent assembly of FtsZ.

PMID- 9553073
TI  - Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+
      uptake into mitochondria in vitro and in situ in single cardiac myocytes.
AB  - Ruthenium red is a well known inhibitor of Ca2+ uptake into mitochondria in
      vitro. However, its utility as an inhibitor of Ca2+ uptake into mitochondria in
      vivo or in situ in intact cells is limited because of its inhibitory effects on
      sarcoplasmic reticulum Ca2+ release channel and other cellular processes. We have
      synthesized a ruthenium derivative and found it to be an oxygen-bridged dinuclear
      ruthenium amine complex. It has the same chemical structure as Ru360 reported
      previously (Emerson, J., Clarke, M. J., Ying, W-L., and Sanadi, D. R. (1993) J.
      Am. Chem. Soc. 115, 11799-11805). Ru360 has been shown to be a potent inhibitor
      of Ca2+-stimulated respiration of liver mitochondria in vitro. However, the
      specificity of Ru360 on Ca2+ uptake into mitochondria in vitro or in intact cells
      has not been determined. The present study reports in detail the potency, the
      effectiveness, and the mechanism of inhibition of mitochondrial Ca2+ uptake by
      Ru360 and its specificity in vitro in isolated mitochondria and in situ in
      isolated cardiac myocytes. Ru360 was more potent (IC50 = 0.184 nM) than ruthenium
      red (IC50 = 6.85 nM) in inhibiting Ca2+ uptake into mitochondria. 103Ru360 was
      found to bind to isolated mitochondria with high affinity (Kd = 0.34 nM, Bmax =
      80 fmol/mg of mitochondrial protein). The IC50 of 103Ru360 for the inhibition of
      Ca2+ uptake into mitochondria was also 0.2 nM, indicating that saturation of a
      specific binding site is responsible for the inhibition of Ca2+ uptake. Ru360, as
      high as 10 microM, produced no effect on sarcoplasmic reticulum Ca2+ uptake or
      release, sarcolemmal Na+/Ca2+ exchange, actomyosin ATPase activity, L-type Ca2+
      channel current, cytosolic Ca2+ transients, or cell shortening. 103Ru360 was
      taken up by isolated myocytes in a time-dependent biphasic manner. Ru360 (10
      microM) applied outside intact voltage-clamped ventricular myocytes prevented
      Ca2+ uptake into mitochondria in situ where the cells were progressively loaded
      with Ca2+ via sarcolemmal Na+/Ca2+ exchange by depolarization to +110 mV. We
      conclude that Ru360 specifically blocks Ca2+ uptake into mitochondria and can be
      used in intact cells.

PMID- 9553074
TI  - Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival
      in response to tumor necrosis factor alpha.
AB  - Fas ligand and tumor necrosis factor alpha (TNF) bind to members of the TNF
      receptor superfamily. Stimulation by Fas ligand results in apoptosis, whereas TNF
      induces multiple effects including proliferation, differentiation, and apoptosis.
      Activation of the c-Jun N-terminal kinase (JNK) and p38 kinase pathways is common
      to Fas and TNF signaling; however, their role in apoptosis is controversial. Fas
      receptor cross-linking induces apoptosis in the absence of actinomycin D and
      activates JNK in a caspase-dependent manner. In contrast, TNF requires
      actinomycin D for apoptosis and activates JNK and p38 kinase with biphasic
      kinetics. The first phase is transient, precedes apoptosis, and is caspase
      independent, whereas the second phase is coincident with apoptosis and is caspase
      dependent. Inhibition of early TNF-induced JNK and p38 kinases using MKK4/MKK6
      mutants or the p38 inhibitor SB203580 increases TNF-induced apoptosis, whereas
      expression of wild type MKK4/MKK6 enhances survival. In contrast, the Mek
      inhibitor PD098059 has no effect on survival. These results demonstrate that
      early activation of p38 kinase (but not Mek) are necessary to protect cells from
      TNF-mediated cytotoxicity. Thus, early stress kinase activation initiated by TNF
      plays a key role in regulating apoptosis.

PMID- 9553075
TI  - The C2 domains of Rabphilin3A specifically bind phosphatidylinositol 4,5
      bisphosphate containing vesicles in a Ca2+-dependent manner. In vitro
      characteristics and possible significance.
AB  - In the present study we investigated the lipid binding characteristics of the C2
      domains of Rabphilin3a. We found that the tandem C2 domain of Rabphilin3a
      specifically bound lipid vesicles containing phosphatidylinositol 4,5
      bisphosphate (PtdIns(4,5)P2) in a Ca2+-dependent manner. There was little binding
      to vesicles containing PtdIns(3,4)P2 in the presence or absence of Ca2+. Binding
      to phosphatidylinositol 3,4,5-triphosphate-containing vesicles was similar to
      binding to PtdIns(4,5)P2-containing vesicles. The presence of physiological
      amounts of phosphatidylserine (PS) greatly potentiated the ability of
      PtdIns(4,5)P2 to cause vesicle binding. As with the C2 domains together, the
      binding of individual C2 domain of Rabphilin3a was much greater to PtdIns(4,5)P2
      containing vesicles than PtdIns(3,4)P2-containing vesicles. Both C2 domains also
      bound 29 mol % PS-containing vesicles in a Ca2+-dependent manner. Because of the
      importance of the C2B domain in the enhancement of secretion from chromaffin
      cells by Rabphilin3a, its biochemistry was further investigated. The mutation of
      aspartates 657 and 659 to asparagines in C2B decreased Ca2+-dependent and
      increased Ca2+-independent vesicle binding, indicating the Ca2+ dependence of the
      domain is provided by aspartic acid residues in the putative Ca2+-binding pocket.
      A peptide from the COOH-terminal region of the C2B domain specifically inhibited
      ATP-dependent secretion from permeabilized chromaffin cells and the binding of
      Rabphilin3a to phosphatidylcholine/PS/PtdIns(4,5)P2-containing lipid vesicles,
      suggesting a role of this sequence in secretion through its ability to interact
      with acidic lipid vesicles.

PMID- 9553076
TI  - The N terminus of eukaryotic translation elongation factor 3 interacts with 18 S
      rRNA and 80 S ribosomes.
AB  - Elongation factor-3 (EF-3) is an essential fungal-specific translation factor
      which exhibits a strong ribosome-dependent ATPase activity and has sequence
      homologies that may predict domains critical for its role in protein synthesis,
      including a domain at the N terminus, which exhibits sequence homology with
      Escherichia coli ribosomal protein S5. A portion of the N terminus of
      Saccharomyces cerevisiae EF-3 (spanning the S5 homology region) has been cloned,
      expressed, and purified from E. coli. UV cross-linking experiments revealed that
      the N-terminal EF-3 protein (N-term EF-3) can be specifically cross-linked to 18
      S rRNA. Filter-binding assays confirmed these data, and also established that the
      interaction has a Kd approximately 238 nM. Additional evidence shows that N-term
      EF-3 is able to associate with yeast ribosomes and inhibit the ribosome-dependent
      ATPase activity of native EF-3. These data taken together suggest that at least
      one of the ribosome-binding sites of EF-3 is located at the N terminus.

PMID- 9553077
TI  - Template strand switching by T7 RNA polymerase.
AB  - T7 RNA polymerase (RNAP) is able to traverse a variety of discontinuities in the
      template (T) strand of duplex DNA, including nicks, gaps, and branched junctions
      in which the 3' end of the T strand is not complementary to the non-template (NT)
      strand. The products represent a faithful copy of the T strand, with no
      insertions or deletions. On double-stranded templates having protruding 3' ends
      the polymerase is able to insert the free 3' end of the NT strand and to utilize
      this as a new T strand ("turn around transcription"), resulting in the anomalous
      production of high molecular weight transcripts. The capacity of T7 RNAP to
      bypass interruptions in the T strand depends upon the stability of the elongation
      complex. Sequences that are expected to stabilize a local RNA:DNA hybrid (such as
      the presence of a C6 tract in the T strand) dramatically reduce dissociation of
      the RNAP while still allowing the enzyme to insert a new 3' end. Similar effects
      on RNAP release are observed when the enzyme reaches the end of a template (i.e.
      when synthesizing runoff products), resulting in markedly different yields of RNA
      product during multiple rounds of transcription.

PMID- 9553078
TI  - Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2
      and ErbB4 expression in neonatal and adult ventricular myocytes.
AB  - Neuregulins (i.e. neuregulin-1 (NRG1), also called neu differentiation factor,
      heregulin, glial growth factor, and acetylcholine receptor-inducing activity) are
      known to induce growth and differentiation of epithelial, glial, neuronal, and
      skeletal muscle cells. Unexpectedly, mice with loss of function mutations of NRG1
      or of either of two of their cognate receptors, ErbB2 and ErbB4, die during
      midembryogenesis due to the aborted development of myocardial trabeculae in
      ventricular muscle. To examine the role of NRG and their receptors in developing
      and postnatal myocardium, we studied the ability of a soluble NRG1 (recombinant
      human glial growth factor 2) to promote proliferation, survival, and growth of
      isolated neonatal and adult rat cardiac myocytes. Both ErbB2 and ErbB4 receptors
      were found to be expressed by neonatal and adult ventricular myocytes and
      activated by rhGGF2. rhGGF2 (30 ng/ml) provoked an approximate 2-fold increase in
      embryonic cardiac myocyte proliferation. rhGGF2 also promoted survival and
      inhibited apoptosis of subconfluent, serum-deprived myocyte primary cultures and
      also induced hypertrophic growth in both neonatal and adult ventricular myocytes,
      which was accompanied by enhanced expression of prepro-atrial natriuretic factor
      and skeletal alpha-actin. Moreover, NRG1 mRNA could be detected in coronary
      microvascular endothelial cell primary cultures prepared from adult rat
      ventricular muscle. NRG1 expression in these cells was increased by endothelin-1,
      another locally acting cardiotropic peptide within the heart. The persistent
      expression of both a neuregulin and its cognate receptors in the postnatal and
      adult heart suggests a continuing role for neuregulins in the myocardial adaption
      to physiologic stress or injury.

PMID- 9553079
TI  - A novel multifunctional motif in the amino-terminal A/B domain of T3Ralpha
      modulates DNA binding and receptor dimerization.
AB  - We reported previously that deletion of the 50-amino acid NH2-terminal A/B domain
      of the chicken (c) or rat thyroid hormone (T3) receptor-alpha (T3Ralpha)
      decreased the T3-dependent stimulation of genes regulated by native thyroid
      hormone response elements (TREs). This requirement of the NH2-terminal A/B domain
      for transcriptional activation was mapped to amino acids 21-30 of cT3Ralpha.
      Expression of transcription factor IIB (TFIIB) in cells was shown to enhance T3
      dependent transcriptional activation by cT3Ralpha, and this enhancement by TFIIB
      was dependent on the same 10-amino acid sequence. In vitro binding studies
      indicated that cT3Ralpha interacts efficiently with TFIIB, and this interaction
      requires amino acids 23KRKRK27 in the A/B domain. In this study we document the
      functional importance of these five basic residues in transcriptional activation
      by cT3Ralpha, further supporting the biological significance of these residues
      and their interaction with TFIIB. Interestingly, we also find that the same amino
      acids also affect DNA binding and dimerization of cT3Ralpha. Gel mobility shift
      assays reveal that a cT3Ralpha mutant that has all five basic amino acids changed
      from 23KRKRK27 to 23TITIT27 binds to a palindromic TRE predominantly as a
      homodimer, whereas cT3Ralpha with the wild-type 23KRKRK27 sequence binds
      predominantly as a monomer. This results from both a marked decrease in the
      ability of the cT3Ralpha mutant to bind as a monomer and from an enhanced ability
      to dimerize as reflected by an increase in DNA-bound T3R-retinoic X receptor
      heterodimers. These effects of 23KRKRK27 on DNA binding, dimerization,
      transcriptional activation, and the association of T3Ralpha with TFIIB support
      the notion that this basic amino acid motif may influence the overall structure
      and function of T3Ralpha and, thus, play a role in determining the distinct
      context-dependent transactivation potentials of the individual T3R isoforms.

PMID- 9553080
TI  - Molecular cloning and functional characterization of a novel receptor-activated
      TRP Ca2+ channel from mouse brain.
AB  - Characterization of mammalian homologues of Drosophila TRP proteins, which induce
      light-activated Ca2+ conductance in photoreceptors, has been an important clue to
      understand molecular mechanisms underlying receptor-activated Ca2+ influx in
      vertebrate cells. We have here isolated cDNA that encodes a novel TRP homologue,
      TRP5, predominantly expressed in the brain. Recombinant expression of the TRP5
      cDNA in human embryonic kidney cells dramatically potentiated extracellular Ca2+
      dependent rises of intracellular Ca2+ concentration ([Ca2+]i) evoked by ATP.
      These [Ca2+]i transients were inhibited by SK&F96365, a blocker of receptor
      activated Ca2+ entry, and by La3+. Expression of the TRP5 cDNA, however, did not
      significantly affect [Ca2+]i transients induced by thapsigargin, an inhibitor of
      endoplasmic reticulum Ca2+-ATPases. ATP stimulation of TRP5-transfected cells
      pretreated with thapsigargin to deplete internal Ca2+ stores caused intact
      extracellular Ca2+-dependent [Ca2+]i transients, whereas ATP suppressed [Ca2+]i
      in thapsigargin-pretreated control cells. Furthermore, in ATP-stimulated, TRP5
      expressing cells, there was no significant correlation between Ca2+ release from
      the internal Ca2+ store and influx of extracellular Ca2+. Whole-cell mode of
      patch-clamp recording from TRP5-expressing cells demonstrated that ATP
      application induced a large inward current in the presence of extracellular Ca2+.
      Omission of Ca2+ from intrapipette solution abolished the current in TRP5
      expressing cells, whereas 10 nM intrapipette Ca2+ was sufficient to support TRP5
      activity triggered by ATP receptor stimulation. Permeability ratios estimated
      from the zero-current potentials of this current were PCa:PNa:PCs = 14.3:1. 5:1.
      Our findings suggest that TRP5 directs the formation of a Ca2+-selective ion
      channel activated by receptor stimulation through a pathway that involves Ca2+
      but not depletion of Ca2+ store in mammalian cells.

PMID- 9553081
TI  - The effect of F-actin on the binding and hydrolysis of guanine nucleotide by
      Dictyostelium elongation factor 1A.
AB  - Indirect evidence implicates actin as a cofactor in eukaryotic protein synthesis.
      The present study directly examines the effects of F-actin on the biochemical
      properties of eukaryotic elongation factor 1A (eEF1A, formerly EF1alpha), a major
      actin-binding protein. The basal mechanism of eEF1A alone is determined under
      physiological conditions with the critical finding that glycerol and guanine
      nucleotide are required to prevent protein aggregation and loss of enzymatic
      activity. The dissociation constants (Kd) for GDP and GTP are 2.5 microM and 0.6
      microM, respectively, and the kcat of GTP hydrolysis is 1.0 x 10(-3) s-1. When
      eEF1A binds to F-actin, there is a 7-fold decrease in the affinity for guanine
      nucleotide and an increase of 35% in the rate of GTP hydrolysis. Based upon our
      results and the relevant cellular concentrations, the predominant form of
      cellular eEF1A is calculated to be GTP.eEF1A.F-actin. We conclude that F-actin
      does not significantly modulate the basal enzymatic properties of eEF1A; however,
      actin may still influence protein synthesis by sequestering GTP.eEF1A away from
      interactions with its known translational ligands, e.g. aminoacyl-tRNA and
      ribosomes.

PMID- 9553082
TI  - Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome biogenesis disorders
      and identification of the point mutation underlying a single enzyme deficiency.
AB  - Peroxisomes play an indispensible role in ether lipid biosynthesis as evidenced
      by the deficiency of ether phospholipids in fibroblasts and tissues from patients
      suffering from a number of peroxisomal disorders. Alkyl-dihydroxyacetonephosphate
      synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether
      phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal
      cleavable presequence. Using a polyclonal antiserum raised against alkyl
      dihydroxyacetonephosphate synthase, levels of this enzyme were examined in
      fibroblast cell lines from patients affected by peroxisomal disorders. Strongly
      reduced levels were found in fibroblasts of Zellweger syndrome and rhizomelic
      chondrodysplasia punctata patients, indicating that the enzyme is not stable in
      the cytoplasm as a result of defective import into peroxisomes. In a neonatal
      adrenoleukodystrophy patient with an isolated import deficiency of proteins
      carrying the peroxisomal targeting signal type 1, the precursor form of alkyl
      dihydroxyacetonephosphate synthase was detected at a level comparable to that of
      the mature form in control fibroblasts, in line with an intraperoxisomal
      localization. A patient with an isolated deficiency in alkyl
      dihydroxyacetonephosphate (DHAP) synthase activity had normal levels of this
      protein. Analysis at the cDNA level revealed a missense mutation leading to a
      R419H substitution in the enzyme of this patient. Expression of a recombinant
      protein carrying this mutation in Escherichia coli yielded an inactive enzyme,
      whereas a comparable control recombinant enzyme was active, providing further
      proof that this substitution is responsible for the inactivity of the enzyme and
      the phenotype. In line with this result is the observation that wild-type alkyl
      DHAP synthase activity can be inactivated by the arginine-modifying agent
      phenylglyoxal. The enzyme is efficiently protected against this inactivation when
      the substrate palmitoyl-DHAP is present at a saturating concentration. The gene
      encoding human alkyl-dihydroxyacetonephosphate synthase was mapped on chromosome
      2q31.

PMID- 9553083
TI  - Reconstitution of a protein disulfide catalytic system.
AB  - Disulfide bonds are important for the structure and stability of many proteins.
      In prokaryotes their formation is catalyzed by the Dsb proteins. The DsbA protein
      acts as a direct donor of disulfides to newly synthesized periplasmic proteins.
      Genetic evidence suggests that a second protein called DsbB acts to specifically
      reoxidize DsbA. Here we demonstrate the direct reoxidation of DsbA by DsbB. We
      have developed a fluorescence assay that allows us to directly follow the
      reoxidation of DsbA. We show that membranes containing catalytic amounts of DsbB
      can rapidly reoxidize DsbA to completion. The reaction strongly depends on the
      presence of oxygen, implying that oxygen serves as the final electron acceptor
      for this disulfide bond formation reaction. Membranes from a dsbB null mutant
      display no DsbA reoxidation activity. The ability of DsbB to reoxidize DsbA fits
      Michaelis-Menten behavior with DsbA acting as a high affinity substrate for DsbB
      with a Km = 10 microM. The in vitro reconstitution described here is the first
      biochemical analysis of DsbB and allows us to study the major pathway of
      disulfide bond formation in Escherichia coli.

PMID- 9553084
TI  - Positively charged residues at positions 12, 17, and 18 of glucagon ensure
      maximum biological potency.
AB  - Glucagon is a peptide hormone that plays a central role in the maintenance of
      normal circulating glucose levels. Structure-activity studies have previously
      demonstrated the importance of histidine at position 1 and the absolute
      requirement for aspartic acid at position 9 for transduction of the hormonal
      signal. Site-directed mutagenesis of the receptor protein identified Asp64 on the
      extracellular N-terminal tail to be crucial for the recognition function of the
      receptor. In addition, antibodies generated against aspartic acid-rich epitopes
      from the extracellular region competed effectively with glucagon for receptor
      sites, which suggested that negative charges may line the putative glucagon
      binding pocket in the receptor. These observations led to the idea that
      positively charged residues on the hormone may act as counterions to these sites.
      Based on these initial findings, we synthesized glucagon analogs in which basic
      residues at positions 12, 17, and 18 were replaced with neutral or acidic
      residues to examine the effect of altering the positive charge on those sites on
      binding and adenylyl cyclase activity. The results indicate that unlike N
      terminal histidine, Lys12, Arg17, and Arg18 of glucagon have very large effects
      on receptor binding and transduction of the hormonal signal, although they are
      not absolutely critical. They contribute strongly to the stabilization of the
      binding interaction with the glucagon receptor that leads to maximum biological
      potency.

PMID- 9553085
TI  - Growth in iron-enriched medium partially compensates Escherichia coli for the
      lack of manganese and iron superoxide dismutase.
AB  - Enrichment of the growth medium with iron partially relieves the phenotypic
      deficits imposed on Escherichia coli by lack of both manganese and iron
      superoxide dismutases. Thus iron supplementation increased the aerobic growth
      rate, decreased the leakage of sulfite, and diminished sensitivity toward
      paraquat. Iron supplementation increased the activities of several [4Fe-4S]
      containing dehydratases, and this was seen even in the presence of 50 microg/ml
      of rifampicin, an amount which completely inhibited growth. Assessing the O-2
      scavenging activity by means of lucigenin luminescence indicated that the iron
      enriched sodAsodB cells had gained some means of eliminating O-2, which was not
      detectable as superoxide dismutase activity in cell extracts. It is noteworthy
      that iron-enriched cells were not more sensitive toward the lethality of H2O2
      despite having the usual amount of catalase activity. This indicates that iron
      taken into the cells from the medium is not available for Fenton chemistry, but
      is available for reconstitution of iron-sulfur clusters. We suppose that
      oxidation of the [4Fe-4S] clusters of dehydratases by O-2 and their subsequent
      reductive reconstitution provides a mechanism for scavenging O-2 and that
      speeding this reductive reconstitution by iron enrichment both spared other
      targets from O-2 attack and maintained adequate levels of these enzymes to meet
      the metabolic needs of the cells.

PMID- 9553086
TI  - Seven novel mammalian SNARE proteins localize to distinct membrane compartments.
AB  - Soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE)
      proteins of the vesicle-associated membrane protein (VAMP) and syntaxin families
      play a central role in vesicular trafficking through the formation of complexes
      between proteins present on vesicle and target membranes. Formation of these
      complexes is proposed to mediate aspects of the specificity of vesicle
      trafficking and to promote fusion of the lipid bilayers. In order to further
      understand the molecular mechanisms that organize membrane compartments, we have
      characterized seven new mammalian proteins of the VAMP and syntaxin families. The
      proteins are broadly expressed; however, syntaxin 13 is enriched in brain and
      VAMP 8 in kidney. The seven novel SNAREs localize in distinct patterns
      overlapping with Golgi, endosomal, or lysosomal markers. Our studies support the
      hypothesis that evolutionary radiation of these two gene families gave rise to
      sets of proteins whose differential expression and combinatorial associations
      define and organize the membrane compartments of cells.

PMID- 9553087
TI  - Identification and characterization of a novel cap-binding protein from
      Arabidopsis thaliana.
AB  - Cap-binding proteins specifically bind to the 7-methyl guanosine (m7G) functional
      group at the 5' end of eukaryotic mRNAs. A novel Arabidopsis thaliana protein has
      been identified that has sequence similarity to cap-binding proteins but is
      clearly a different form of the protein. The most obvious primary sequence
      difference is the substitution of two of the eight conserved tryptophan residues
      with other aromatic amino acids in the novel protein. Analogous forms of this
      novel protein appear to be present in other higher eukaryotes but not in yeast.
      Analysis of the native and recombinant forms of the novel protein by retention on
      m7GTP-Sepharose indicate that it is a functional cap-binding protein.
      Measurements of the dissociation constant for this protein indicate that it binds
      m7GTP 5-20-fold tighter than eukaryotic initiation factor (eIF)(iso)4E. The novel
      protein also supports the initiation of translation of capped mRNA in vitro.
      Biochemical analysis and yeast two-hybrid data indicate that it interacts with
      eIF(iso)4G to form a complex. Based on these observations, this protein appears
      to be able to function as a cap-binding protein and is given the designation of
      novel cap-binding protein (nCBP).

PMID- 9553088
TI  - Identification of intron and exon sequences involved in alternative splicing of
      insulin receptor pre-mRNA.
AB  - The insulin receptor exists as two isoforms, A and B, that result from
      alternative splicing of exon 11 in the primary transcript. We have shown
      previously that the alternative splicing is developmentally and hormonally
      regulated. Consequently, these studies were instigated to identify sequences
      within the primary RNA transcript that regulate the alternative splicing.
      Minigenes containing exons 10, 11, and 12 and the intervening introns were
      constructed and transfected into HepG2 cells, which contain both isoforms of the
      insulin receptor. The cells were able to splice the minigene transcript to give
      both A (- exon 11) and B-like (+ exon 11) RNAs. A series of internal deletions
      within intron 10 were tested for their ability to give A and B RNAs. Intron 10
      contained two sequences that modulated exon 11 inclusion; a 48-nucleotide purine
      rich sequence at the 5' end of intron 10 that functions as a splicing enhancer
      and causes an increase in exon 11 inclusion, and a 43-nucleotide sequence at the
      3' end of intron 10 upstream of the branch point sequence that favors skipping of
      exon 11. Increasing the length of the polypyrimidine tract at the 3' end of
      intron 10 caused exon 11 to be spliced constitutively, indicating that a weak
      splice site is required for alternative splicing. Finally, point mutations,
      insertions, and deletions within exon 11 itself were able to regulate inclusion
      of the exon both positively and negatively.

PMID- 9553089
TI  - Granulocyte-macrophage colony-stimulating factor gene transcription is directly
      repressed by the vitamin D3 receptor. Implications for allosteric influences on
      nuclear receptor structure and function by a DNA element.
AB  - The primary function of activated T lymphocytes is to produce various cytokines
      necessary to elicit an immune response; these cytokines include interleukin-2 (IL
      2), interleukin-4, and granulocyte-macrophage colony-stimulating factor (GMCSF).
      Steroid hormones and vitamin A and D3 metabolites act to repress the expression
      of cytokines. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) down-modulates activated IL
      2 expression at the level transcription, through direct antagonism of the
      transactivating complex NFAT-1/AP-1 by the vitamin D3 receptor (VDR). We report
      here that GMCSF transcription in Jurkat T cells is also directly repressed by 1,
      25-(OH)2D3 and VDR. Among four NFAT/AP-1 elements in the GMCSF enhancer, we have
      focused on one such element that when multimerized, is sufficient in mediating
      both activation by NFAT-1 and AP-1 and repression in response to 1,25-(OH)2D3.
      Although this element does not contain any recognizable vitamin D response
      elements (VDREs), high affinity DNA binding by recombinant VDR is observed. In
      contrast to VDR interactions with positive VDREs, this binding is independent of
      VDR's heterodimeric partner, the retinoid X receptor. Moreover, VDR appears to
      bind the GMCSF element as an apparent monomer in vitro. Protease digestion
      patterns of bound VDR, and receptor mutations affecting DNA binding and
      dimerization, demonstrate that the receptor binds to the negative site in a
      distinct conformation relative to a positive VDRE, suggesting that the DNA
      element itself acts as an allosteric effector of VDR function. This altered
      conformation may account for VDR's action as a repressing rather than activating
      factor at this locus.

PMID- 9553090
TI  - A phosphatidylinositol 3-kinase and phosphatidylinositol transfer protein act
      synergistically in formation of constitutive transport vesicles from the trans
      Golgi network.
AB  - Current evidence suggests that phosphatidylinositol (PI) kinases and
      phosphatidylinositol transfer protein (PITP) are involved in driving vesicular
      traffic from yeast and mammalian trans-Golgi network (TGN). We have tested the
      interaction between these cytosolic proteins in an assay that measures the
      formation of constitutive transport vesicles from the TGN in a hepatocyte cell
      free system. This reaction is dependent on a novel PI 3-kinase, and we now report
      that, under conditions of limiting cytosol, purified PI 3-kinase and PITP
      functionally cooperate to drive exocytic vesicle formation. This synergy was
      observed with both yeast and mammalian PITPs, and it also extended to the
      formation of PI 3-phosphate. These collective findings indicate that the PI 3
      kinase and PITP synergize to form a pool of PI 3-phosphate that is essential for
      formation of exocytic vesicles from the hepatocyte TGN.

PMID- 9553091
TI  - DNA bending by the chromosomal protein HMG1 and its high mobility group box
      domains. Effect of flanking sequences.
AB  - HMG1 is an evolutionarily highly conserved chromosomal protein consisting of two
      folded DNA-binding domains, A and B ("high mobility group (HMG) boxes"), and an
      acidic C-terminal domain. Several lines of evidence suggest that previously
      reported sequence-independent DNA bending and looping by HMG1 and its HMG box
      domains might be important for the proposed role of the protein in transcription
      and recombination. We have used ligase-mediated circularization assays to
      investigate the contribution of the individual A and B HMG1 box domains and of
      the linker region between A/B- and B/C-domains, which flank the "minimal" B
      domain (residues 92-162), to the ability of the HMG1 protein (residues 1-215) to
      bend DNA. Neither the minimal B-domain nor the minimal B-domain with a 7-residue
      N-terminal extension (85TKKKFKD91) bent the DNA. The attachment of an extra 18
      residue C-terminal additional extension (residues 163-180) to the minimal B
      domain had only a small effect on the ability of the HMG box to bend DNA. On the
      other hand, circularization assay with a B-domain having both 7-residue N
      terminal and 18-residue C-terminal flanking sequences (residues 85-180) revealed
      a strong bending of the DNA, suggesting that both extensions are a prerequisite
      for efficient DNA bending by the B-domain. We have also shown that a single
      lysine residue (Lys90) in a short N-terminal sequence 90KD91 attached to the B
      domain is sufficient for strong distortion of DNA by bending, provided that the B
      domain is flanked by the 18-residue C-terminal flanking sequence. Although the
      DNA bending potential of HMG1 seems to be predominantly due to the B-domain
      flanked by basic sequences, covalent attachment of the A- and B-domains is
      necessary for efficient DNA flexure and the ability of the (A+B)-bidomain to bend
      DNA is further modulated in the native HMG1 protein by its acidic C-domain.

PMID- 9553092
TI  - Inhibition of the expression of mitogen-activated protein phosphatase-1
      potentiates apoptosis induced by tumor necrosis factor-alpha in rat mesangial
      cells.
AB  - Previously we showed that rat mesangial cells are normally resistant to tumor
      necrosis factor-alpha (TNF-alpha)-induced apoptosis. They are made susceptible to
      the apoptotic effect of TNF-alpha when pretreated with actinomycin D,
      cycloheximide or vanadate. A sustained c-Jun N-terminal protein kinase (JNK)
      activation was closely correlated with the initiation of apoptosis under these
      conditions. We proposed that a TNF-alpha-inducible phosphatase was responsible
      for preventing a sustained activation of JNK and consequent apoptosis in these
      cells (Guo, Y.-L., Baysal, K., Kang, B. , Yang, L.-J., and Williamson, J. R.
      (1998) J. Biol. Chem. 273, 4027-4034). In the present study we provide further
      evidence to support this hypothesis. Ro318220, although originally identified as
      a specific inhibitor of protein kinase C, was subsequently found to be a strong
      inhibitor of MKP-1 expression. In rat mesangial cells, pretreatment of the cells
      with Ro318220 blocked expression of MKP-1 induced by TNF-alpha. This treatment
      also prolonged JNK activation and caused apoptosis. Taken together, our results
      support the currently controversial hypothesis that the JNK pathway is involved
      in TNF-alpha-induced apoptosis. In addition, we provide a mechanistic explanation
      for how mesangial cells in primary culture achieve resistance to TNF-alpha
      cytotoxicity. Specifically, induction of MKP-1 by TNF-alpha appears to be
      responsible for protection of the cells from apoptosis by preventing a prolonged
      activation of JNK.

PMID- 9553093
TI  - Agonist occupation of an alpha2A-adrenoreceptor-Gi1alpha fusion protein results
      in activation of both receptor-linked and endogenous Gi proteins. Comparisons of
      their contributions to GTPase activity and signal transduction and analysis of
      receptor-G protein activation stoichiometry.
AB  - A fusion protein between a pertussis toxin-resistant (C351G) mutant of the alpha
      subunit of the G protein Gi1 and the porcine alpha2A-adrenoreceptor was stably
      expressed in Rat 1 fibroblasts. Agonists caused stimulation of high affinity
      GTPase activity, which was partially prevented by pertussis toxin treatment,
      demonstrating that the toxin-resistant component of the GTPase activity was
      derived from the receptor-fused G protein and the remainder from endogenous
      Gialpha. Half-maximal stimulation of the GTPase activity of endogenous Gi was
      achieved with lower concentrations of agonist. Although the Km for GTP of the
      fusion protein-linked Gi was lower than for the endogenous G protein, Vmax
      measurements demonstrated that adrenaline activated some 5 mol of endogenous
      Gi/mol of fusion protein-linked Gi. The isolated alpha2A-adrenoreceptor could
      activate Gs; however, the fusion protein did not. Compared with adrenaline, the
      efficacy of a range of partial agonists to stimulate endogenous Gialpha was
      greater than for the fusion protein-constrained C351G Gi1alpha. alpha2A
      Adrenoreceptor agonists could stimulate both p44 mitogen-activated protein kinase
      and p70 S6 kinase and inhibit forskolin-amplified adenylyl cyclase activity in
      untreated alpha2A-adrenoreceptor-C351G Gi1alpha fusion protein-expressing cells,
      but these signals were abolished following pertussis toxin treatment. These
      results demonstrate conclusively, and for the first time, that agonist occupancy
      of a receptor-G protein fusion protein can result in activation of G proteins
      other than that physically linked to the receptor. This was selective between G
      protein classes. Analysis of the contributions of fusion protein-linked and
      endogenous G proteins to agonist-stimulated GTPase activity provided a direct and
      original measure of receptor-G protein activation stoichiometry.

PMID- 9553094
TI  - The baculovirus anti-apoptotic p35 protein promotes transformation of mouse
      embryo fibroblasts.
AB  - The baculovirus p35 protein is a potent inhibitor of programmed cell death
      induced by a variety of stimuli in insects, nematodes, and mammalian cell lines.
      The broad ability of p35 in preventing apoptosis has led us to investigate its
      effect on mouse embryo fibroblasts in vitro and in vivo. For this purpose, we
      have used R- cells (3T3-like fibroblasts derived from mouse embryos with a
      targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes)
      and R508 cells (derived from R- and with 15 x 10(3) IGF-IRs per cell). Both cell
      lines grow normally in monolayer, but they do not form colonies in soft agar, and
      they are non-tumorigenic in nude mice. We show here that, in addition to its anti
      apoptotic effect, p35 causes transformation of R508 cells, as evidenced by the
      following: 1) decreased growth factor requirements, 2) ability to form foci in
      monolayer and colonies in soft agar, and 3) ability to form tumors in nude mice.
      Since R- cells stably transfected with p35 do not transform, our observations
      suggest that in addition to its effect as an inhibitor of apoptosis, the
      baculovirus p35 protein has transforming potential that requires the presence of
      the IGF-IR. The possibility that these two properties could be separated was
      confirmed by demonstrating that R508 cells expressing another anti-apoptotic
      protein, Bcl-2, could not form tumors in nude mice.

PMID- 9553095
TI  - Functional analysis of the Numb phosphotyrosine-binding domain using site
      directed mutagenesis.
AB  - The Numb protein is involved in cell fate determination during Drosophila neural
      development. Numb has a protein domain homologous to the phosphotyrosine-binding
      domain (PTB) in the adaptor protein Shc. In Shc, this domain interacts with
      specific phosphotyrosine containing motifs on receptor tyrosine kinases and other
      signaling molecules. Residues N-terminal to the phosphotyrosine are also crucial
      for phosphopeptide binding to the Shc PTB domain. Several amino acid residues in
      Shc have been implicated by site-directed mutagenesis to be critical for Shc
      binding to receptor tyrosine kinases. We have generated homologous mutations in
      Numb to test whether, in vivo, these changes affect Numb function during
      Drosophila sensory organ development. Two independent amino acid changes that
      interfere with Shc binding to phosphotyrosine residues do not affect Numb
      activity in vivo. In contrast, a mutation shown to abrogate the ability of the
      Shc PTB domain to bind residues upstream of the phosphotyrosine virtually
      eliminates Numb function. Similar results were observed in vitro by examining the
      binding of the Numb PTB domain to proteins from Schneider S2 cells. Our data
      confirm the importance of the PTB domain for Numb function but strongly suggest
      that the Numb PTB domain is not involved in phosphotyrosine-dependent
      interactions.

PMID- 9553096
TI  - Synchronized spontaneous Ca2+ transients in acute anterior pituitary slices.
AB  - We investigated the organization of spontaneous rises in cytosolic free Ca2+
      concentration ([Ca2+]i) due to electrical activity in acute pituitary slices.
      Real time confocal imaging revealed that 73% of the cells generated fast peaking
      spontaneous [Ca2+]i transients. Strikingly, groups of apposing cells enhanced
      their [Ca2+]i in synchrony with a speed of coactivation >1,000 microm/s. Single
      cell injection of Neurobiotin or Lucifer yellow labeled clusters of cells, which
      corresponded to coactive cells. Halothane, a gap junction blocker, markedly
      reduced the spread of tracers. Coupling between excitable cells was mainly
      homologous in nature, with a prevalence of growth hormone-containing cells. We
      conclude that spontaneously active endocrine cells are either single units or
      arranged in synchronized gap junction-coupled assemblies scattered throughout the
      anterior pituitary gland. Synchrony between spontaneously excitable cells may
      help shape the patterns of basal secretion.

PMID- 9553097
TI  - Crystal structure of the von Willebrand Factor A1 domain and implications for the
      binding of platelet glycoprotein Ib.
AB  - von Willebrand Factor (vWF) is a multimeric protein that mediates platelet
      adhesion to exposed subendothelium at sites of vascular injury under conditions
      of high flow/shear. The A1 domain of vWF (vWF-A1) forms the principal binding
      site for platelet glycoprotein Ib (GpIb), an interaction that is tightly
      regulated. We report here the crystal structure of the vWF-A1 domain at 2.3-A
      resolution. As expected, the overall fold is similar to that of the vWF-A3 and
      integrin I domains. However, the structure also contains N- and C-terminal arms
      that wrap across the lower surface of the domain. Unlike the integrin I domains,
      vWF-A1 does not contain a metal ion-dependent adhesion site motif. Analysis of
      the available mutagenesis data suggests that the activator botrocetin binds to
      the right-hand face of the domain containing helices alpha5 and alpha6. Possible
      binding sites for GpIb are the front and upper surfaces of the domain. Natural
      mutations that lead to constitutive GpIb binding (von Willebrand type IIb
      disease) cluster in a different site, at the interface between the lower surface
      and the terminal arms, suggesting that they disrupt a regulatory region rather
      than forming part of the primary GpIb binding site. A possible pathway for
      propagating structural changes from the regulatory region to the ligand-binding
      surface is discussed.

PMID- 9553098
TI  - Characterization of a Ca2+ release-activated nonselective cation current
      regulating membrane potential and [Ca2+]i oscillations in transgenically derived
      beta-cells.
AB  - Although stimulation of insulin secretion by glucose is regulated by coupled
      oscillations of membrane potential and intracellular Ca2+ ([Ca2+]i), the membrane
      events regulating these oscillations are incompletely understood. In the presence
      of glucose and tetraethylammonium, transgenically derived beta-cells (betaTC3
      neo) exhibit coupled voltage and [Ca2+]i oscillations strikingly similar to those
      observed in normal islets in response to glucose. Using these cells as a model
      system, we investigated the membrane conductance underlying these oscillations.
      Alterations in delayed rectifier or Ca2+-activated K+ channels were excluded as a
      source of the conductance oscillations, as they are completely blocked by
      tetraethylammonium. ATP-sensitive K+ channels were also excluded, since the ATP
      sensitive K+ channel blocker tolbutamide substituted for glucose in inducing
      [Ca2+]i oscillations. Thapsigargin, which depletes intracellular Ca2+ stores, and
      maitotoxin, an activator of nonselective cation channels, both converted the
      glucose-dependent [Ca2+]i oscillations into a sustained elevation. On the other
      hand, both SKF 96365, a blocker of Ca2+ store-operated channels, and external Na+
      removal suppressed the glucose-stimulated [Ca2+]i oscillations. Maitotoxin
      activated a nonselective cation current in betaTC3 cells that was attenuated by
      removal of extracellular Na+ and by SKF 96365, in the same manner to a current
      activated in mouse beta-cells following depletion of intracellular Ca2+ stores.
      Currents similar to these are produced by the mammalian trp-related channels, a
      gene family that includes Ca2+ store-operated channels and inositol 1,4,5
      trisphosphate-activated channels. We found several of the trp family genes were
      expressed in betaTC3 cells by reverse transcriptase polymerase chain reaction
      using specific primers, but by Northern blot analysis, mtrp-4 was the predominant
      message expressed. We conclude that a conductance underlying glucose-stimulated
      oscillations in beta-cells is provided by a Ca2+ store depletion-activated
      nonselective cation current, which is plausibly encoded by homologs of trp genes.

PMID- 9553099
TI  - Residues 21-30 within the extracellular N-terminal region of the C5a receptor
      represent a binding domain for the C5a anaphylatoxin.
AB  - The functions of the C5a anaphylatoxin are expressed through its interaction with
      a cell-surface receptor with seven transmembrane helices. The interaction of C5a
      with the receptor has been explained by a two-site model whereby recognition and
      effector sites on C5a bind, respectively, to recognition and effector domains on
      the receptor, leading to receptor activation (Chenoweth, D. E., and Hugli, T. E.
      (1980) Mol. Immunol. 17, 151-161. In addition, the extracellular N-terminal
      region of the C5a receptor has been implicated as the recognition domain for C5a,
      responsible for approximately 50% of the binding energy of the C5a-receptor
      complex (Mery, L., and Boulay, F. (1994) J. Biol. Chem. 269, 3457-3463;
      DeMartino, J. A., Van Riper, G., Siciliano, S. J., Molineaux, C. J., Konteatis,
      Z. D., Rosen, H., and Springer, M. S. (1994) J. Biol. Chem. 269, 14446-14450). In
      this work, the interactions of C5a with the N-terminal domain of the C5a receptor
      were examined by use of recombinant human C5a molecules and peptide fragments
      M1NSFN5YTTPD10YGHYD15DKDTL20DLNTP25VDKTS30NTLR(hC5aRF-1-34), acetyl
      HYD15DKDTL20DLNTP25VDKTS30NTLR (hC5aRF-13-34), and acetyl-TL20DLNTP25VDKTS30N
      amide (hC5aRF-19-31) derived from human C5a receptor. Binding induced resonance
      perturbations in the NMR spectra of the receptor fragments and the C5a molecules
      indicated that the isolated Nterminal domain or residues 1-34 of the C5a receptor
      retain specific binding to C5a and to a C5a analog devoid of the agonistic C
      terminal tail in the intact C5a. Residues of C5a perturbed by the binding of the
      receptor peptides are localized within the helical core of the C5a structure, in
      agreement with the results from functional studies employing mutated C5a and
      intact receptor molecules. All three receptor peptides, hC5aRF-1-34, hC5aRF-13
      34, and hC5aRF-19-31, responded to the binding of C5a through the 21-30 region
      containing either hydrophobic, polar, or positively charged residues such as
      Thr24, Pro25, Val26, Lys28, Thr29, and Ser30. The 21-30 segment of all three
      receptor fragments was found to have a partially folded conformation in solution,
      independent of residues 1-18. These results indicate that a short peptide
      sequence, or residues 21-30, of the C5a receptor N terminus may constitute the
      binding domain for the recognition site on C5a.

PMID- 9553100
TI  - Addressing the tertiary structure of human parathyroid hormone-(1-34).
AB  - Parathyroid hormone (PTH) regulates mineral metabolism and bone turnover by
      activating specific receptors located on osteoblastic and renal tubular cells and
      is fully functional as the N-terminal 1-34 fragment, PTH-(1-34). Previously, a "U
      shaped" conformation with N- and C-terminal helices brought in close proximity by
      a turn has been postulated. The general acceptance of this hypothesis, despite
      limited experimental evidence, has altered the direction of the design of PTH
      analogs. Examining the structure of human PTH-(1-34) under conditions that
      encompass the different environments the hormone may experience in the approach
      to and interaction with the G-protein-coupled receptor (including benign aqueous
      and saline solutions and in the presence of dodecylphosphocholine), we observe no
      evidence for a U-shape conformation or any tertiary structure. Instead, the N-
      and C-terminal helical domains, which vary in length and stability depending on
      the conditions, are separated by a highly flexible region of undefined
      conformation. These observations are in complete accord with recent
      conformational studies of PTH-related protein analogs containing lactams (Mierke,
      D. F., Maretto, S., Schievano, E. , DeLuca, D., Bisello, A., Mammi, S.,
      Rosenblatt, M., Peggion, E., and Chorev, M. (1997) Biochemistry 36, 10372-10383)
      or a model amphiphilic alpha-helix (Pellegrini, M., Bisello, A., Rosenblatt, M.,
      Chorev, M., and Mierke, D. F. (1997) J. Med. Chem. 40, 3025-3031). Reliable
      structural data from different environmental conditions are absolutely requisite
      for the next step in the design of non-peptide PTH analogs.

PMID- 9553101
TI  - Identification of a ligand binding site in the human neutrophil formyl peptide
      receptor using a site-specific fluorescent photoaffinity label and mass
      spectrometry.
AB  - A novel fluorescent photoaffinity cross-linking probe, formyl-Met-p-benzoyl-L
      phenylalanine-Phe-Tyr-Lys-epsilon-N-fluorescei n (fMBpaFYK-fl), was synthesized
      and used to identify binding site residues in recombinant human phagocyte
      chemoattractant formyl peptide receptor (FPR). After photoactivation, fluorescein
      labeled membranes from Chinese hamster ovary cells were solubilized in
      octylglucoside and separated by tandem anion exchange and gel filtration
      chromatography. A single peak of fluorescence was observed in extracts of FPR
      expressing cells that was absent in extracts from wild type controls.
      Photolabeled Chinese hamster ovary membranes were cleaved with CNBr, and the
      fluorescent fragments were isolated on an antifluorescein immunoaffinity matrix.
      Matrix-assisted laser desorption ionization mass spectrometry identified a major
      species with mass = 1754, consistent with the CNBr fragment of fMBpaFYK-fl cross
      linked to Val-Arg-Lys-Ala-Hse (an expected CNBr fragment of FPR, residues 83-87).
      This peptide was further cleaved with trypsin, repurified by antifluorescein
      immunoaffinity, and subjected to matrix-assisted laser desorption ionization mass
      spectrometry. A tryptic fragment with mass = 1582 was observed, which is the mass
      of fMBpaFYK-fl cross-linked to Val-Arg-Lys (FPR residues 83-85), an expected
      trypsin cleavage product of Val-Arg-Lys-Ala-Hse. Residues 83-85 lie within the
      putative second transmembrane-spanning region of FPR near the extracellular
      surface. A 3D model of FPR is presented, which accounts for intramembrane, site
      directed mutagenesis results (Miettinen, H. M., Mills, J., Gripentrog, J., Dratz,
      E. A., Granger, B. L., and Jesaitis, A. J. (1997) J. Immunol. 159, 4045-4054) and
      the photochemical cross-linking data.

PMID- 9553102
TI  - Mitogen-activated protein kinase pathway is involved in the differentiation of
      muscle cells.
AB  - The differentiation of muscle cells is controlled by the MyoD family of
      transcription factors. This family is regulated by extracellular growth factors
      that transmit largely unknown signals into the cells. Here we show that the
      activity of extracellular signal-regulated protein kinase (ERK), a kinase that is
      part of the mitogen-activated protein kinase (MAPK) cascade, is low in myoblasts
      and is induced with the onset of terminal differentiation of C2 cells. ERK
      activity is also induced in fibroblasts that were modified to express MyoD, but
      not in the parental fibroblast cells. Thus, ERK induction is an intrinsic
      property of muscle cells. A specific MAPK kinase inhibitor (PD098059) that was
      added to C2 cells partially inhibited the fusion of myoblasts to multinucleated
      myotubes without affecting the expression of muscle-specific markers. This
      inhibitor blocked the induction of MyoD expression that normally takes place
      during terminal differentiation. Two lines of evidence suggest that the MAPK
      cascade induces the activity of MyoD: 1) the expression of constitutively
      activated forms of MEK1 or Raf1 enhanced the transcriptional activity of MyoD in
      10T1/2 fibroblasts; and 2) the addition of PD098059 to fibroblast cells
      expressing a conditional MyoD-estrogen fusion protein significantly inhibited the
      expression of MyoD-responsive genes. Our results indicate that the MAPK pathway
      is activated in differentiating muscle cells and that it positively regulates the
      expression and activity of MyoD protein.

PMID- 9553103
TI  - Functional microdomains in G-protein-coupled receptors. The conserved arginine
      cage motif in the gonadotropin-releasing hormone receptor.
AB  - An Arg present in the third transmembrane domain of all rhodopsin-like G-protein
      coupled receptors is required for efficient signal transduction. Mutation of this
      Arg in the gonadotropin-releasing hormone receptor to Gln, His, or Lys abolished
      or severely impaired agonist-stimulated inositol phosphate generation, consistent
      with Arg having a role in receptor activation. To investigate the contribution of
      the surrounding structural domain in the actions of the conserved Arg, an
      integrated microdomain modeling and mutagenesis approach has been utilized. Two
      conserved residues that constrain the Arg side chain to a limited number of
      conformations have been identified. In the inactive wild-type receptor, the Arg
      side chain is proposed to form an ionic interaction with Asp3.49(138).
      Experimental results for the Asp3. 49(138) --> Asn mutant receptor show a
      modestly enhanced receptor efficiency, consistent with the hypothesis that
      weakening the Asp3. 49(138)-Arg3.50(139) interaction by protonation of the Asp or
      by the mutation to Asn favors activation. With activation, the Asp3. 49(138)
      Arg3.50(139) ionic bond would break, and the unrestrained Arg would be prevented
      from orienting itself toward the water phase by a steric clash with Ile3.54(143).
      The mutation Ile3.54(143) --> Ala, which eliminates this clash in simulations,
      causes a marked reduction in measured receptor signaling efficiency, implying
      that solvation of Arg3.50(139) prevents it from functioning in the activation of
      the receptor. These data are consistent with residues Asp3.49(138) and
      Ile3.54(143) forming a structural motif, which helps position Arg in its
      appropriate inactive and active receptor conformations.

PMID- 9553104
TI  - Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine
      phosphatase by x-ray crystallography.
AB  - Protein-tyrosine phosphatases (PTPs) are signal transduction enzymes that
      catalyze the dephosphorylation of phosphotyrosine residues via the formation of a
      transient cysteinyl-phosphate intermediate. The mechanism of hydrolysis of this
      intermediate has been examined by generating a Gln-262 --> Ala mutant of PTP1B,
      which allows the accumulation and trapping of the intermediate within a PTP1B
      crystal. The structure of the intermediate at 2.5-A resolution reveals that a
      conformationally flexible loop (the WPD loop) is closed over the entrance to the
      catalytic site, sequestering the phosphocysteine intermediate and catalytic site
      water molecules and preventing nonspecific phosphoryltransfer reactions to
      extraneous phosphoryl acceptors. One of the catalytic site water molecules, the
      likely nucleophile, forms a hydrogen bond to the putative catalytic base, Asp
      181. In the wild-type enzyme, the nucleophilic water molecule would be
      coordinated by the side chain of Gln-262. In combination with our previous
      structural data, we can now visualize each of the reaction steps of the PTP
      catalytic pathway. The hydrolysis of the cysteinyl-phosphate intermediate of PTPs
      is reminiscent of GTP hydrolysis by the GTPases, in that both families of enzymes
      utilize an invariant Gln residue to coordinate the attacking nucleophilic water
      molecule.

PMID- 9553105
TI  - In vivo regulation of the IkappaB homologue cactus during the immune response of
      Drosophila.
AB  - The dorsoventral regulatory gene pathway (spatzle/Toll/cactus) controls the
      expression of several antimicrobial genes during the immune response of
      Drosophila. This regulatory cascade shows striking similarities with the cytokine
      induced activation cascade of NF-kappaB during the inflammatory response in
      mammals. Here, we have studied the regulation of the IkappaB homologue Cactus in
      the fat body during the immune response. We observe that the cactus gene is up
      regulated in response to immune challenge. Interestingly, the expression of the
      cactus gene is controlled by the spatzle/Toll/cactus gene pathway, indicating
      that the cactus gene is autoregulated. We also show that two Cactus isoforms are
      expressed in the cytoplasm of fat body cells and that they are rapidly degraded
      and resynthesized after immune challenge. This degradation is also dependent on
      the Toll signaling pathway. Altogether, our results underline the striking
      similarities between the regulation of IkappaB and cactus during the immune
      response.

PMID- 9553106
TI  - Acrosin accelerates the dispersal of sperm acrosomal proteins during acrosome
      reaction.
AB  - Using homologous recombination, we have previously produced male mice carrying a
      disruptive mutation (Acr-/-) in the acrosin gene. Although Acr-/- mouse sperm
      lacking the acrosin protease activity still penetrated the zona pellucida and
      fertilized the egg, the mutant sperm exhibited a delay in penetration of the zona
      pellucida solely at the early stages after insemination. To further elucidate the
      role of acrosin in fertilization, we have examined the involvement of acrosin in
      the acrosome reaction of sperm using the Acr-/- mutant mice. When the ability of
      sperm to adhere (attach) and bind to the zona pellucida of cumulus-free eggs was
      assessed in vitro, no significant difference was observed among Acr+/+, Acr+/-,
      and Acr-/- mouse sperm. Immunocytochemical analysis demonstrated that the release
      of several acrosomal proteins from the acrosome of Acr-/- mouse sperm was
      significantly delayed during the calcium ionophore- and solubilized zona
      pellucida-induced acrosome reaction, despite normal membrane vesiculation. These
      data indicate that the delayed sperm penetration of the zona pellucida in the Acr
      /- mouse results from the altered rate of protein dispersal from the acrosome and
      provide the first evidence that the major role of acrosin is to accelerate the
      dispersal of acrosomal components during acrosome reaction.

PMID- 9553107
TI  - Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases.
AB  - Grb10 and its close homologues Grb7 and Grb14, belong to a family of adapter
      proteins characterized by a proline-rich region, a central PH domain, and a
      carboxyl-terminal Src homology 2 (SH2) domain. Their interaction with a variety
      of activated tyrosine kinase receptors is well documented, but their actual
      function remains a mystery. The Grb10 SH2 domain was isolated from a two-hybrid
      screen using the MEK1 kinase as a bait. We show that this unusual SH2 domain
      interacts, in a phosphotyrosine-independent manner, with both the Raf1 and MEK1
      kinases. Mutation of the MEK1 Thr-386 residue, which is phosphorylated by mitogen
      activated protein kinase in vitro, reduces binding to Grb10 in a two-hybrid
      assay. Interaction of Grb10 with Raf1 is constitutive, while interaction between
      Grb10 and MEK1 needs insulin treatment of the cells and follows mitogen-activated
      protein kinase activation. Random mutagenesis of the SH2 domain demonstrated that
      the Arg-betaB5 and Asp-EF2 residues are necessary for binding to the epidermal
      growth factor and insulin receptors as well as to the two kinases. In addition,
      we show that a mutation in Ser-betaB7 affects binding only to the receptors,
      while a mutation in Thr-betaC5 abrogates binding only to MEK1. Finally,
      transfection of Grb10 genes with specific mutations in their SH2 domains induces
      apoptosis in HTC-IR and COS-7 cells. These effects can be competed by co
      expression of the wild type protein, suggesting that these mutants act by
      sequestering necessary signaling components.

PMID- 9553108
TI  - Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of
      the amyloid precursor protein.
AB  - Caveolae are plasma membrane invaginations where key signaling elements are
      concentrated. In this report, both biochemical and histochemical analyses
      demonstrate that the amyloid precursor protein (APP), a source of Abeta amyloid
      peptide, is enriched within caveolae. Caveolin-1, a principal component of
      caveolae, is physically associated with APP, and the cytoplasmic domain of APP
      directly participates in this binding. The characteristic C-terminal fragment
      that results from APP processing by alpha-secretase, an as yet unidentified
      enzyme that cleaves APP within the Abeta amyloid sequence, was also localized
      within these caveolae-enriched fractions. Further analysis by cell surface
      biotinylation revealed that this cleavage event occurs at the cell surface.
      Importantly, alpha-secretase processing was significantly promoted by recombinant
      overexpression of caveolin in intact cells, resulting in increased secretion of
      the soluble extracellular domain of APP. Conversely, caveolin depletion using
      antisense oligonucletotides prevented this cleavage event. Our current results
      indicate that caveolae and caveolins may play a pivotal role in the alpha
      secretase-mediated proteolysis of APP in vivo.

PMID- 9553109
TI  - Epiregulin is a potent pan-ErbB ligand that preferentially activates
      heterodimeric receptor complexes.
AB  - The ErbB signaling network consists of four transmembrane receptor tyrosine
      kinases and more than a dozen ligands sharing an epidermal growth factor (EGF)
      motif. The multiplicity of ErbB-specific ligands is incompletely understood in
      terms of signal specificity because all ErbB molecules signal through partially
      overlapping pathways. Here we addressed the action of epiregulin, a recently
      isolated ligand of ErbB-1. By employing a set of factor-dependent cell lines
      engineered to express individual ErbBs or their combinations, we found that
      epiregulin is the broadest specificity EGF-like ligand so far characterized: not
      only does it stimulate homodimers of both ErbB-1 and ErbB-4, it also activates
      all possible heterodimeric ErbB complexes. Consistent with its relaxed
      selectivity, epiregulin binds the various receptor combinations with an affinity
      that is approximately 100-fold lower than the affinity of ligands with more
      stringent selectivity, including EGF. Nevertheless, epiregulin's action upon most
      receptor combinations transmits a more potent mitogenic signal than does EGF.
      This remarkable discrepancy between binding affinity and bioactivity is permitted
      by a mechanism that prevents receptor down-regulation, and results in a weak, but
      prolonged, state of receptor activation.

PMID- 9553110
TI  - Interaction of transcription factors with serum response factor. Identification
      of the Elk-1 binding surface.
AB  - Serum response elements (SREs) play important roles in transforming extracellular
      signals into specific nuclear responses. The SRE-binding protein, serum response
      factor (SRF), plays a pivotal role in this process. Several transcription factors
      have been shown to interact with SRF and thereby create distinct complexes with
      different regulatory potentials. The ETS domain transcription factor Elk-1 is one
      such protein and serves to integrate distinct mitogen-activated protein kinase
      cascades at SREs. Elk-1 uses a short hydrophobic surface presented on the surface
      of an alpha-helix to interact with SRF. In this study we have used site-directed
      mutagenesis to identify residues in SRF that comprise the Elk-1 binding surface.
      The Elk-1 binding surface is composed of residues that lie on a hydrophobic
      surface-exposed groove located at the junction of the MADS box and C-terminal SAM
      motif. Different residues are implicated in interactions between SRF and the
      transcription factor Fli-1, indicating that although some overlap with the Elk-1
      binding surface occurs, their interaction surfaces on SRF are distinct. Our data
      are consistent with the hypothesis that the SRF DNA-binding domain acts as
      docking site for multiple transcription factors that can bind to small surface
      exposed patches within this domain.

PMID- 9553111
TI  - Does single-stranded DNA pass through the inner channel of the protein hexamer in
      the complex with the Escherichia coli DnaB Helicase? Fluorescence energy transfer
      studies.
AB  - The structure of the complex of the Escherichia coli primary replicative helicase
      DnaB protein with single-stranded (ss) DNA and replication fork substrates has
      been examined using the fluorescence energy transfer method. In these
      experiments, we used the DnaB protein variant, R14C, which has arginine 14
      replaced by cysteine in the small 12-kDa domain of the protein using site
      directed mutagenesis. The cysteine residues have been modified with a fluorescent
      marker which serves as a donor or an acceptor to another fluorescence label
      placed in different locations on the DNA substrates. Using the multiple
      fluorescence donor-acceptor approach, we provide evidence that, in the complex
      with the enzyme, ssDNA passes through the inner channel of the DnaB hexamer. This
      is the first evidence of the existence of such a structure of a hexameric
      helicase-ssDNA complex in solution. In the stationary complex with the 5' arm of
      the replication fork, without ATP hydrolysis, the distance between the 5' end of
      the arm and the 12-kDa domains of the hexamer (R = 47 A) is the same as in the
      complex with the isolated ssDNA oligomer (R = 47 A) having the same length as the
      arm of the fork. These data indicate that both ssDNA and the 5' arm of the fork
      bind in the same manner to the DNA binding site. Moreover, in the complex with
      the helicase, the length of the ssDNA is similar to the length of the ssDNA
      strand in the double-stranded DNA conformation. In the stationary complex, the
      helicase does not invade the duplex part of the fork beyond the first 2-3 base
      pairs. This result corroborates the quantitative thermodynamic data which showed
      that the duplex part of the fork does not contribute to the free energy of
      binding of the enzyme to the fork. Implications of these results for the
      mechanism of a hexameric helicase binding to DNA are discussed.

PMID- 9553112
TI  - Molecular cloning, characterization, and promoter analysis of the mouse
      Crp2/SmLim gene. Preferential expression of its promoter in the vascular smooth
      muscle cells of transgenic mice.
AB  - Several members of the LIM protein family have important roles in development and
      differentiation. We recently isolated a rat cDNA encoding a new member of this
      family, CRP2/SmLIM, that contains two LIM domains and is expressed preferentially
      in vascular smooth muscle cells (VSMC). To study the molecular mechanisms that
      regulate VSMC-specific transcription of the Crp2/SmLim gene, we cloned the cDNA
      and gene of mouse Crp2/SmLim. Mouse Crp2/SmLim is a single copy gene of six exons
      and five introns spanning approximately 20 kilobases of genomic DNA. By 5'-rapid
      amplification of cDNA ends and S1 nuclease protection assay, we determined that
      the transcription start site is an A residue 80 base pairs 5' of the translation
      initiation codon. A TATA-like sequence is located 27 base pairs 5' of the
      transcription start site, and there are potential cis-acting elements (GATA, Sp1,
      AP-2, E box, CCAC box, and GArC motif) in the 5'-flanking sequence. In transient
      transfection assays in rat aortic smooth muscle cells in primary culture, 5
      kilobases of the Crp2/SmLim 5'-flanking sequence generated a high level of
      luciferase reporter gene activity. By deletion analysis and gel mobility shift
      assay, we found that the region between bases -74 and -39 of this 5 kilobase DNA
      fragment binds Sp1 and confers basal promoter activity in the Crp2/SmLim gene. In
      vitro, the 5-kilobase fragment was active in multiple cell types. In vivo,
      however, the 5-kilobase fragment directed high level expression of the lacZ
      reporter gene preferentially in the VSMC of transgenic mice, indicating the
      presence of VSMC-specific element(s) in this fragment.

PMID- 9553113
TI  - Multiple isoforms of eukaryotic protein synthesis initiation factor 4E in
      Caenorhabditis elegans can distinguish between mono- and trimethylated mRNA cap
      structures.
AB  - The rate-limiting step for cap-dependent translation initiation in eukaryotes is
      recruitment of mRNA to the ribosome. An early event in this process is
      recognition of the m7GTP-containing cap structure at the 5'-end of the mRNA by
      initiation factor eIF4E. In the nematode Caenorhabditis elegans, mRNAs from 70%
      of the genes contain a different cap structure, m32,2,7GTP. This cap structure is
      poorly recognized by mammalian elF4E, suggesting that C. elegans may possess a
      specialized form of elF4E that can recognize m32,2,7GTP. Analysis of the C.
      elegans genomic sequence data base revealed the presence of three elF4E-like
      genes, here named ife-1, ife-2, and ife-3. cDNAs for these three eIF4E isoforms
      were cloned and sequenced. Isoform-specific antibodies were prepared from
      synthetic peptides based on nonhomologous regions of the three proteins. All
      three eIF4E isoforms were detected in extracts of C. elegans and were retained on
      m7GTP-Sepharose. One eIF4E isoform, IFE-1, was also retained on m32,2,7GTP
      Sepharose. Furthermore, binding of IFE-1 and IFE-2 to m7GTP-Sepharose was
      inhibited by m32,2,7GTP. These results suggest that IFE-1 and IFE-2 bind both
      m7GTP- and m32,2, 7GTP-containing mRNA cap structures, although with different
      affinities. In conjunction with IFE-3, these eIF4E isoforms would permit cap
      dependent recruitment of all C. elegans mRNAs to the ribosome.

PMID- 9553115
TI  - The role of an inverted CCAAT element in transcriptional activation of the human
      DNA topoisomerase IIalpha gene by heat shock.
AB  - Expression of the DNA topoisomerase IIalpha (topoIIalpha) gene is highly
      sensitive to various environmental stimuli including heat shock. The amount of
      topoIIalpha mRNA was increased 1.5-3-fold 6-24 h after exposure of T24 human
      urinary bladder cancer cells to heat shock stress at 43 degreesC for 1 h. The
      effect of heat shock on the transcriptional activity of the human topoIIalpha
      gene promoter was investigated by transient transfection of T24 cells with
      luciferase reporter plasmids containing various lengths of the promoter sequence.
      The transcriptional activity of the full-length promoter (nucleotides (nt) -295
      to +85) and of three deletion constructs (nt -197 to +85, -154 to +85, and -74 to
      +85) was increased approximately 3-fold 24 h after heat shock stress. In
      contrast, the transcriptional activity of the minimal promoter (nt -20 to +85),
      which lacks the first inverted CCAAT element (ICE1), the GC box, and the heat
      shock element located between nt -74 and -21, was not increased by heat shock.
      Furthermore, the transcriptional activity of promoter constructs containing
      mutations in the GC box or heat shock element, but not that of a construct
      containing mutations in ICE1, was significantly increased by heat shock.
      Electrophoretic mobility shift assays revealed reduced binding of a nuclear
      factor to an oligonucleotide containing ICE1 when nuclear extracts were derived
      from cells cultured for 3-24 h after heat shock. No such change in factor binding
      was apparent with an oligonucleotide containing the heat shock element of the
      topoIIalpha gene promoter. Finally, in vivo footprint analysis of the topoIIalpha
      gene promoter revealed that two G residues of ICE1 that were protected in control
      cells became sensitive to dimethyl sulfate modification after heat shock. These
      results suggest that transcriptional activation of the topoIIalpha gene by heat
      shock requires the release of a negative regulatory factor from ICE1.

PMID- 9553114
TI  - Expression and conservation of apolipoprotein AIV in an avian species.
AB  - In birds, intestinally derived lipoproteins are thought to be secreted directly
      into the portal vein rather than to enter the circulation via the lymphatic
      system as in mammals. Hepatic clearance of these so-called portomicrons must be
      rapid, but the protein(s) mediating their catabolism, presumably analogues of the
      36-kDa mammalian apolipoprotein E, have not been identified. In searching for
      such a mediator(s), we have isolated a hitherto unknown 38-kDa protein from
      chicken serum, which we identified by microsequencing and molecular cloning as a
      counterpart to mammalian apolipoprotein AIV (apoAIV). Mature chicken apoAIV
      consists of 347 amino acids, lacks cysteine residues, and displays 57% sequence
      identity with human apoAIV and, to a significantly lesser extent, with apoAIVs of
      rodents. This first nonmammalian apoAIV characterized is the smallest homologue
      reported so far, because of the lack of repeated motifs at the carboxyl terminus
      with the consensus sequence Glu-Gln-Glu/Ala-Gln, a hallmark of mammalian apoAIVs.
      Chicken apoAIV (isoelectric point, 4.65) is also considerably more acidic than
      its human counterpart. Agarose gel electrophoresis revealed that unlike human
      apoAIV, which migrates to a pre-alpha-position, chicken apoAIV shows fast alpha
      migration. Functional characterization demonstrated that the avian protein is
      able to activate the enzyme lecithin:cholesterol acyltransferase. Roosters and
      hens express apoAIV predominantly in the gut, one-fifth as much in the liver, and
      no other sites of expression are identifiable by Northern blot analysis. Although
      pronounced intestinal synthesis is common to apoAIVs, the features of the avian
      protein support the notion that it represents a prototype of an apoprotein that
      evolved to acquire possibly distinct functions in mammals and birds.

PMID- 9553116
TI  - Two signaling mechanisms for activation of alphaM beta2 avidity in
      polymorphonuclear neutrophils.
AB  - Circulating polymorphonuclear neutrophils (PMN) are quiescent, nonadherent cells
      that rapidly activate at sites of inflammation, where they develop the capacity
      to perform a repertoire of functions that are essential for host defense.
      Induction of integrin-mediated adhesion, which requires an increase in integrin
      avidity, is critical for the development of these effector functions. Although a
      variety of stimuli can activate integrins in PMN, the signaling cascades involved
      are unclear. Phosphatidylinositol (PI) 3-kinase has been implicated in integrin
      activation in a variety of cells, including PMN. In this work, we have examined
      activation of the PMN integrin alphaM beta2, assessing both adhesion and
      generation of the epitope recognized by the activation-specific antibody CBRM1/5.
      We have found that PI 3-kinase has a role in activation of alphaM beta2 by immune
      complexes, but we have found no role for it in alphaM beta2 activation by ligands
      for trimeric G protein-coupled receptors, including
      formylmethionylleucylphenylalanine (fMLP), interleukin-8, and C5a. Cytochalasin D
      inhibition suggests a role for the actin cytoskeleton in immune complex
      activation of alphaM beta2, but cytochalasin has no effect on fMLP-induced
      activation. Similarly, immune complex activation of the Rac/Cdc42-dependent
      serine/threonine kinase Pak1 is blocked by PI 3-kinase inhibitors, but fMLP
      induced activation is not. These results demonstrate that two signaling pathways
      exist in PMN for activation of alphaM beta2. One, induced by FcgammaR ligation,
      is PI 3-kinase-dependent and requires the actin cytoskeleton. The second,
      initiated by G protein-linked receptors, is PI 3-kinase-independent and
      cytochalasin-insensitive. Pak1 may be in a final common pathway leading to
      activation of alphaM beta2.

PMID- 9553117
TI  - Modulation of protein splicing of the Saccharomyces cerevisiae vacuolar membrane
      ATPase intein.
AB  - Protein splicing of the Saccharomyces cerevisiae vacuolar membrane ATPase intein
      involves four highly coordinated reactions that result in precise cleavage and
      formation of peptide bonds. In this study, we investigated the roles of the last
      N-extein residue (-1 residue) and the intein penultimate residue in modulating
      splicing reactions. Most of the 20 amino acid substitutions at the -1 position
      had no effect on overall protein splicing but could lead to significant
      accumulation of thioester intermediates when splicing was blocked by mutation. A
      subset of -1 substitutions attenuated the initiation of protein splicing and
      enabled us to demonstrate in vitro splicing of a mesophilic intein containing all
      wild-type catalytic residues. Substitutions involving the intein penultimate
      residue allowed modulation of the branch resolution and C-terminal cleavage
      reaction. Our data suggest that the N-S acyl rearrangement, which initiates
      splicing, may also serve as the rate-limiting step. Through appropriate amino
      acid substitutions, we were able to modulate splicing reactions in vitro by
      change in pH or temperature or addition of thiol reagents. Both insertion and
      deletion were tolerated in the central region of the intein although splicing or
      structure of the intein may have been affected.

PMID- 9553118
TI  - The M4M5 cytoplasmic loop of the Na,K-ATPase, overexpressed in Escherichia coli,
      binds nucleoside triphosphates with the same selectivity as the intact native
      protein.
AB  - Escherichia coli was used to overexpress the large cytoplasmic loop of the rat
      Na,K-ATPase. A 1260-base DNA segment encoding Lys354-Lys774 of the rat alpha1
      subunit was constructed via polymerase chain reaction. The polymerase chain
      reaction product was successfully subcloned into the expression vector pET-28
      (Novagen), which produces an N-terminal 6-histidine-tagged fusion protein. The
      pET-28 vector containing rat alpha-loop, i.e. pAN, was used to transform calcium
      competent E. coli BL21(DE3) cells, and positive clones were selected by kanamycin
      resistance. Bacterial cultures were grown, and protein synthesis was induced with
      isopropyl beta-D-thiogalactoside. Cells were harvested and lysed, revealing
      production of the His-tagged fusion protein ( approximately 46 kDa). The fusion
      protein was affinity-purified from other soluble cellular proteins via a Ni-NTA
      column, which routinely yielded approximately 20 mg of soluble His6-alpha-loop/L
      cell culture. The His6-alpha-loop retained significant native structure, as
      evidenced by the ability of ATP and ADP (but not AMP, CTP, GTP, or UTP) to
      protect against chemical modification by either fluorescein isothiocyanate or
      maleimidylanilinonapthalene sulfonic acid. More specifically, circular dichroism
      spectroscopy was used to estimate the secondary structure of the His6 loop,
      revealing an ordered folding composed of 23% alpha-helix, 23% antiparallel beta
      sheet, 4% parallel beta-sheet, 19% beta-turn, and 32% random coil. The 6
      histidine loop bound the fluorescent ATP analog trinitrophenyl-ATP with high
      affinity, as determined by measuring the fluorescence changes associated with
      binding. Affinities for ATP ( approximately 350 microM) and ADP ( approximately
      550 microM) were determined by their ability to compete with and displace 2',3'-O
      [2,4,6,-trinitrophenyl]-ATP. These nucleotide affinities are similar to those
      observed for the E2 conformation of the intact Na,K-ATPase.

PMID- 9553119
TI  - Transcriptional regulation of insulin-like growth factor-II gene expression by
      cortisol in fetal sheep during late gestation.
AB  - The objective of this study was to determine the mechanisms by which cortisol
      down-regulates hepatic insulin-like growth factor-II (IGF-II) gene expression in
      late gestation. Leader exons 6 and 7 of the ovine IGF-II gene, with their 5'
      flanking regions, were first isolated. Characterization of transcription start
      sites revealed a unique site for exon 6 and three dispersed sites for exon 7.
      Nuclear run-on assays showed a 5-fold higher transcription rate of the IGF-II
      gene in liver of adrenalectomized fetuses compared with control animals,
      suggesting that regulation of IGF-II gene expression by cortisol is at the
      transcriptional level. RNase protection assays demonstrated hepatic leader exon 7
      expression in adrenalectomized fetuses to be more than 2-fold higher than in
      controls, whereas it was reduced by 50% in cortisol-infused fetuses compared with
      controls. There was no effect on the expression of other leader exons. Functions
      of the upstream regulatory region of leader exon 7 (i.e. promoter P4) were
      investigated by luciferase transient expression. A region of -172 bases
      downstream relative to the first transcription site of leader exon 7 was shown to
      retain basal promoter activity and respond to cortisol. These results suggest
      that cortisol may induce the prenatal decline in ovine hepatic IGF-II expression
      by suppressing promoter P4 of the IGF-II gene.

PMID- 9553120
TI  - Regulatory properties of the NH2- and COOH-terminal domains of troponin T. ATPase
      activation and binding to troponin I and troponin C.
AB  - The contraction of skeletal muscle is regulated by Ca2+ binding to troponin C,
      which results in an internal reorganization of the interactions within the
      troponin-tropomyosin complex. Troponin T is necessary for Ca2+-dependent
      inhibition and activation of actomyosin. Troponin T consists of an extended NH2
      terminal domain that interacts with tropomyosin and a globular COOH-terminal
      domain that interacts with tropomyosin, troponin I, and troponin C. In this study
      we used recombinant troponin T and troponin I fragments to delimit further the
      structural and regulatory interactions with the thin filament. Our results show
      the following: (i) the NH2-terminal region of troponin T activates the actomyosin
      ATPase in the presence of tropomyosin; (ii) the interaction of the globular
      domain of troponin T with the thin filament blocks ATPase activation in the
      absence of Ca2+; and (iii) the COOH-terminal region of the globular domain
      anchors the troponin C-troponin I binary complex to troponin T through a direct
      Ca2+-independent interaction with the NH2-terminal region of troponin I. This
      interaction is required for Ca2+-dependent activation of the actomyosin ATPase
      activity. Based on these results we propose a refined model for the troponin
      complex and its interaction with the thin filament.

PMID- 9553121
TI  - Tenascin-C hexabrachion assembly is a sequential two-step process initiated by
      coiled-coil alpha-helices.
AB  - We have investigated the oligomerization process of tenascin-C using a variety of
      recombinant wild-type and mutant polypeptide chain fragments produced by
      heterologous gene expression in Escherichia coli. Biochemical and biophysical
      analyses of the structures and assemblies of these fragments indicated a
      sequential two-step oligomerization mechanism of tenascin-C involving the
      concerted interaction of two distinct domains and cysteines 64, 111, and 113.
      First, the sequence between alanine 114 and glutamine 139 initiates hexabrachion
      formation via a parallel three-stranded coiled coil. Subsequently, the tenascin
      assembly domain, which is unique to the tenascins, is responsible for the
      connection of two triplets to a hexamer. The oligomerization of the tenascin
      assembly domains by the three-stranded coiled coil increases their homophilic
      binding affinity and is an important prerequisite for tenascin-C hexamerization.
      Although formation of the characteristic hexabrachion structure involves the
      covalent linkage of the six subunits by cysteine residues, mutational analysis
      indicates that hexamer formation is not dependent on intermolecular disulfide
      bonds. Most interestingly, substitution of glutamate 130 within the coiled-coil
      domain by leucine or alanine resulted in the formation of parallel four-stranded
      helix structures, which further associated to dodecamers. Aside from supporting a
      sequential process of tenascin-C assembly, this finding provides experimental
      evidence that non-core residues can have profound effects on the oligomerization
      states of coiled coils.

PMID- 9553122
TI  - Importance of glucose-6-phosphate dehydrogenase activity for cell growth.
AB  - The intracellular redox potential, which is determined by the level of oxidants
      and reductants, has been shown to play an important role in the regulation of
      cell growth. The principal intracellular reductant is NADPH, which is mainly
      produced by the pentose phosphate pathway through the actions of glucose-6
      phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate
      pathway, and by 6-phosphogluconate dehydrogenase. Previous research has suggested
      that an increase in G6PD activity is important for cell growth. In this article,
      we suggest that G6PD activity plays a critical role in cell growth by providing
      NADPH for redox regulation. The results show the following: 1) inhibition of G6PD
      activity abrogated growth factor stimulation of [3H]thymidine incorporation in
      all cell lines tested; 2) overexpression of G6PD stimulated cell growth, as
      measured by an increase in [3H]thymidine incorporations as compared with cells
      transfected with vector alone; 3) inhibition of G6PD caused cells to be more
      susceptible to the growth inhibitory effects of H2O2; 4) inhibition of G6PD led
      to a 30-40% decrease in the NADPH/NADP ratio; and 5) inhibition of G6PD inhibited
      cell anchorage and significantly decreased the growth-related stimulation of
      tyrosine phosphorylation.

PMID- 9553124
TI  - Syndecan-4 proteoglycan cytoplasmic domain and phosphatidylinositol 4,5
      bisphosphate coordinately regulate protein kinase C activity.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP2) is involved in the organization of
      the actin cytoskeleton by regulating actin-associated proteins. The transmembrane
      heparan sulfate proteoglycan syndecan-4 also plays a critical role in protein
      kinase C (PKC) signaling in the formation of focal adhesions and actin stress
      fibers. The cytoplasmic domain of syndecan-4 core protein directly interacts with
      and potentiates PKCalpha activity, and it can directly interact with the phos-
      phoinositide PIP2. We, therefore, investigated whether the interaction of
      inositol phosphates and inositol phospholipids with syndecan-4 could regulate PKC
      activity. Data from in vitro kinase assays using purified PKCalpha beta gamma
      show that in the absence of phosphatidylserine and diolein, PIP2 increased the
      extent of autophosphorylation of PKCalpha beta gamma and partially activated it
      to phosphorylate both histone III-S and an epidermal growth factor receptor
      peptide. This activity was dose-dependent, and its calcium dependence varied with
      PKC isotype/source. Addition of the cytoplasmic syndecan-4 peptide, but not
      equivalent syndecan-1 or syndecan-2 peptides, potentiated the partial activation
      of PKCalpha beta gamma by PIP2, resulting in activity greater than that observed
      with phosphatidylserine, diolein, and calcium. This study indicates that syndecan
      4 cytoplasmic domain may bind both PIP2 and PKCalpha, localize them to forming
      focal adhesions, and potentiate PKCalpha activity there.

PMID- 9553123
TI  - Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces
      p53-independent transcriptional regulation of p21(WAF1/CIP1) in human prostate
      carcinoma cells.
AB  - Progression through the cell cycle is controlled by the induction of cyclins and
      the activation of cognate cyclin-dependent kinases. The 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin induces growth
      arrest and cell death in certain cancer cell types. We have pursued the mechanism
      of growth arrest in PC-3-M cells, a p53-null human prostate carcinoma cell line.
      Lovastatin treatment increased protein and mRNA levels of the cyclin-dependent
      kinase inhibitor p21(WAF1/CIP1), increased binding of p21 with Cdk2, markedly
      inhibited cyclin E- and Cdk2-associated phosphorylation of histone H1 or GST
      retinoblastoma protein, enhanced binding of the retinoblastoma protein to the
      transcription factor E2F-1 in vivo, and induced the activation of a p21 promoter
      reporter construct. By using p21 promoter deletion constructs, the lovastatin
      responsive element was mapped to a region between -93 and -64 relative to the
      transcription start site. Promoter mutation analysis indicated that the
      lovastatin-responsive site coincided with the previously identified transforming
      growth factor-beta-responsive element. These data indicate that in human prostate
      carcinoma cells an inhibitor of the HMG-CoA reductase pathway can circumvent the
      loss of wild-type p53 function and induce critical downstream regulatory events
      leading to transcriptional activation of p21.

PMID- 9553125
TI  - Oxidation of catalase by singlet oxygen.
AB  - Different bands of catalase activity in zymograms (Cat-1a-Cat-1e) appear during
      Neurospora crassa development and under stress conditions. Here we demonstrate
      that singlet oxygen modifies Cat-1a, giving rise to a sequential shift in
      electrophoretic mobility, similar to the one observed in vivo. Purified Cat-1a
      was modified with singlet oxygen generated from a photosensitization reaction;
      even when the reaction was separated from the enzyme by an air barrier, a
      condition in which only singlet oxygen can reach the enzyme by diffusion.
      Modification of Cat-1a was hindered when reducing agents or singlet oxygen
      scavengers were present in the photosensitization reaction. The sequential
      modification of the four monomers gave rise to five active catalase conformers
      with more acidic isoelectric points. The pI of purified Cat-1a-Cat-1e decreased
      progressively, and a similar shift in pI was observed as Cat-1a was modified by
      singlet oxygen. No further change was detected once Cat-1e was reached. Catalase
      modification was traced to a three-step reaction of the heme. The heme of Cat-1a
      gave rise to three additional heme peaks in a high performance liquid
      chromatography when modified to Cat-1c. Full oxidation to Cat-1e shifted all
      peaks into a single one. Absorbance spectra were consistent with an increase in
      asymmetry as heme was modified. Bacterial, fungal, plant, and animal catalases
      were all susceptible to modification by singlet oxygen, indicating that this is a
      general feature of the enzyme that could explain in part the variety of catalases
      seen in several organisms and the modifications observed in some catalases.
      Modification of catalases during development and under stress could indicate in
      vivo generation of singlet oxygen.

PMID- 9553126
TI  - Identification of a vitamin D response element in the proximal promoter of the
      chicken carbonic anhydrase II gene.
AB  - The carbonic anhydrase II gene, whose transcription is enhanced by 1, 25
      dihydroxyvitamin D3 (1,25-(OH)2D3), encodes an important enzyme in bone-resorbing
      cells derived from the fusion of monocytic progenitors. We analyzed the 1,25
      (OH)2D3-mediated activation of the avian gene by transient transfection assays
      with promoter/reporter constructs into HD11 chicken macrophages and by DNA
      mobility shift assays. Deletion and mobility shift analyses indicated that the 
      62/-29 region confers 1,25-(OH)2D3 responsiveness and forms DNA-protein
      complexes. The addition of an anti-vitamin D receptor (VDR) antibody inhibited
      binding to this sequence, whereas anti-retinoid X receptor (RXR) antibody
      generated a lower mobility complex. Therefore, we concluded that this element
      binds a VDR.RXR heterodimer, but the addition of extra 1,25-(OH)2D3 had no effect
      on the formation of this complex. Moreover, the use of nuclear extracts from 1,25
      (OH)2D3-treated macrophages led to the formation of an additional high mobility
      complex also composed of VDR.RXR heterodimer. Mutations provided evidence that
      the 1, 25-(OH)2D3-mediated activation of the carbonic anhydrase II gene is
      mediated by VDR.RXR heterodimers bound to a DR3-type vitamin D response element
      with sequence AGGGCAtggAGTTCG. This vitamin D response element is also functional
      in the ROS 17/2.8 osteoblasts.

PMID- 9553127
TI  - Parathyroid hormone regulates the rat collagenase-3 promoter in osteoblastic
      cells through the cooperative interaction of the activator protein-1 site and the
      runt domain binding sequence.
AB  - Parathyroid hormone induces collagenase-3 gene transcription in rat osteoblastic
      cells. Here, we characterized the basal, parathyroid hormone regulatory regions
      of the rat collagenase-3 gene and the proteins involved in this regulation. The
      minimal parathyroid hormone-responsive region was observed to be between base
      pairs -38 and -148. Deleted and mutated constructs showed that the activator
      protein-1 and the runt domain binding sites are both required for basal
      expression and parathyroid hormone activation of this gene. The runt domain site
      is identical to an osteoblast-specific element-2 or acute myelogenous leukemia
      binding sequence in the mouse and rat osteocalcin genes, respectively.
      Overexpression of an acute myelogenous leukemia-1 repressor protein inhibited
      parathyroid hormone activation of the promoter, indicating a requirement of acute
      myelogenous leukemia-related factor(s) for this activity. Overexpression of c
      Fos, c-Jun, osteoblast-specific factor-2, and core binding factor-beta increased
      the response to parathyroid hormone of the wild type (-148) promoter but not with
      mutation of either or both the activator protein-1 and runt domain binding sites.
      In summary, we conclude that there is a cooperative interaction of acute
      myelogenous leukemia/polyomavirus enhancer-binding protein-2-related factor(s)
      binding to the runt domain binding site with members of the activator protein-1
      transcription factor family binding to the activator protein-1 site in the rat
      collagenase-3 gene in response to parathyroid hormone in osteoblastic cells.

PMID- 9553128
TI  - Identification of a hormonally regulated luteinizing hormone/human chorionic
      gonadotropin receptor mRNA binding protein. Increased mrna binding during
      receptor down-regulation.
AB  - To elucidate the molecular events associated with the regulation of luteinizing
      hormone/human chorionic gonadotropin (LH/hCG) receptor mRNA stability during hCG
      induced receptor down-regulation, we have identified an LH/hCG receptor-specific
      mRNA binding protein. Proteins were isolated from control and down-regulated rat
      ovary and were incubated with in vitro transcribed RNAs corresponding to the full
      length LH/hCG receptor, as well as 5'- and 3'-truncated receptor forms. Resultant
      ribonucleoprotein complexes were analyzed by RNA gel mobility shift. A prominent
      Mr 50,000 ribonucleoprotein complex was identified with the following
      characteristics: 1) specificity for LH/hCG receptor open reading frame sequences
      located between nucleotides 102 and 282; 2) lack of competition by nonspecific
      RNAs; 3) a 3-fold increase in RNA binding activity during hCG-induced receptor
      down-regulation; and 4) limited tissue expression. This report describes the
      first evidence of an LH/hCG receptor mRNA binding protein, which we term LRBP-1,
      for luteinizing hormone receptor RNA binding protein-1. This protein is a
      candidate for a trans-acting factor involved in the hormonal regulation of LH/hCG
      receptor mRNA stability in rat ovary.

PMID- 9553129
TI  - Identity of the residues responsible for the species-restricted complement
      inhibitory function of human CD59.
AB  - The membrane-anchored glycoprotein CD59 inhibits assembly of the C5b-9 membrane
      attack complex (MAC) of human complement. This inhibitory function of CD59 is
      markedly selective for MAC assembled from human complement components C8 and C9,
      and CD59 shows little inhibitory function toward MAC assembled from rabbit and
      many other non-primate species. We have used this species selectivity of CD59 to
      identify the residues regulating its complement inhibitory function: cDNA of
      rabbit CD59 was cloned and used to express human/rabbit CD59 chimeras in murine
      SV-T2 cells. Plasma membrane expression of each CD59 chimera was quantified by
      use of a 5'-TAG peptide epitope, and each construct was tested for its ability to
      inhibit assembly of functional MAC from human versus rabbit C8 and C9. These
      experiments revealed that the species selectivity of CD59 is entirely determined
      by sequence contained between residues 42 and 58 of the human CD59 polypeptide,
      whereas chimeric substitution outside this peptide segment has little effect on
      the MAC inhibitory function of CD59. Substitution of human CD59 residues 42-58
      into rabbit CD59 resulted in a molecule that was functionally indistinguishable
      from native human CD59, whereas the complementary construct (corresponding
      residues of rabbit CD59 substituted into human CD59) was functionally
      indistinguishable from rabbit CD59. Based on the solved solution structure of
      CD59, these data suggest that selectivity for human C8 and C9 resides in a
      cluster of closely spaced side chains on the surface of CD59 contributed by
      His44, Asn48, Asp49, Thr51, Thr52, Arg55, and Glu58 of the polypeptide.

PMID- 9553130
TI  - High affinity binding of latent matrix metalloproteinase-9 to the alpha2(IV)
      chain of collagen IV.
AB  - Association of matrix metalloproteinases (MMPs) with the cell surface and with
      areas of cell-matrix contacts is critical for extracellular matrix degradation.
      Previously, we showed the surface association of pro-MMP-9 in human breast
      epithelial MCF10A cells. Here, we have characterized the binding parameters of
      pro-MMP-9 and show that the enzyme binds with high affinity (Kd approximately 22
      nM) to MCF10A cells and other cell lines. Binding of pro-MMP-9 to MCF10A cells
      does not result in zymogen activation and is not followed by ligand
      internalization, even after complex formation with tissue inhibitor of
      metalloproteinase-1 (TIMP-1). A 190-kDa cell surface protein was identified by
      ligand blot analysis and affinity purification with immobilized pro-MMP-9.
      Microsequencing and immunoblot analysis revealed that the 190-kDa protein is the
      alpha2(IV) chain of collagen IV. Specific pro-MMP-9 surface binding was competed
      with purified alpha2(IV) and was significantly reduced after treatment of the
      cells with active MMP-9 before the binding assay since alpha2(IV) is hydrolyzed
      by MMP-9. A pro-MMP-9.TIMP-1 complex and MMP-9 bind to alpha2(IV), suggesting
      that neither the C-terminal nor the N-terminal domain of the enzyme is directly
      involved in alpha2(IV) binding. The closely related pro-MMP-2 exhibits a weaker
      affinity for alpha2(IV) compared with that of pro-MMP-9, suggesting that sites
      other than the gelatin-binding domain may be involved in the binding of
      alpha2(IV) to pro-MMP-9. Although pro-MMP-9 forms a complex with alpha2(IV), the
      proenzyme does not bind to triple-helical collagen IV. These studies suggest a
      unique interaction between pro-MMP-9 and alpha2(IV) that may play a role in
      targeting the zymogen to cell-matrix contacts and in the degradation of the
      collagen IV network.

PMID- 9553131
TI  - Growth hormone stimulates the tyrosine phosphorylation and association of p125
      focal adhesion kinase (FAK) with JAK2. Fak is not required for stat-mediated
      transcription.
AB  - We have demonstrated that growth hormone (GH) activates focal adhesion kinase
      (FAK), and this activation results in the tyrosine phosphorylation of two FAK
      substrates, paxillin and tensin. The activation of FAK is time-dependent (maximal
      activation at 5-15 min) and dose-dependent (maximal activation at 0.05 nM). FAK
      and paxillin are constitutively associated in the unstimulated state, remain
      associated during the stimulation phase, and recruit tyrosine-phosphorylated
      tensin to the complex after GH stimulation. Half of the carboxyl-terminal region
      of the GH receptor is dispensable for FAK activation, but FAK activation does
      require the proline-rich box 1 region of the GH receptor, indicative that FAK is
      downstream of JAK2. FAK associates with JAK2 but not JAK1 after GH stimulation of
      cells. Using FAK-replete and FAK-deficient cells, we also show that FAK is not
      required for STAT-mediated transcriptional activation by GH. The use of FAK in
      the signal transduction pathway utilized by GH may be central to many of the
      pleiotropic effects of GH, including cytoskeletal reorganization, cell migration,
      chemotaxis, mitogenesis, and/or prevention of apoptosis and gene transcription.

PMID- 9553132
TI  - Multiple signaling pathways of human interleukin-8 receptor A. Independent
      regulation by phosphorylation.
AB  - Interleukin-8 (IL-8) receptor A (CXCR1) couples to a pertussis toxin-sensitive G
      protein to mediate phospholipase Cbeta (PLCbeta) activation and cellular
      responses. Responses to CXCR1 are attenuated by prior exposure of neutrophils to
      either IL-8, a cleavage product of the fifth component of complement (C5a) or n
      formylated peptides (formylmethionylleucylphenylalanine, fMLP). To characterize
      the role of receptor phosphorylation in the regulation of the CXCR1, a
      phosphorylation-deficient mutant, M2CXCR1, was constructed. This receptor, stably
      expressed in RBL-2H3 cells, coupled more efficiently to G protein and stimulated
      enhanced phosphoinositide hydrolysis, cAMP production, exocytosis, and
      phospholipase D activation, and was resistant to IL-8-induced receptor
      internalization. The rate and total amount of ligand stimulated actin
      polymerization remained unchanged, but interestingly, chemotaxis was decreased by
      approximately 30% compared with the wild type receptor. To study the role of
      receptor phosphorylation in cross-desensitization of chemoattractant receptors,
      M2CXCR1 was coexpressed with cDNAs encoding receptors for either fMLP (FR), C5a
      (C5aR), or platelet-activating factor (PAFR). Both C5aR and PAFR were cross
      phosphorylated upon M2CXCR1 activation, resulting in attenuated guanosine 5'-3'-O
      (thio)triphosphate (GTPgammaS) binding in membranes. In contrast, FR and M2CXCR1
      were resistant to cross-phosphorylation and cross-inhibition of GTPgammaS binding
      by other receptors. Despite the resistance of M2CXCR1 to cross-phosphorylation
      and receptor/G protein uncoupling, its susceptibility to cross-desensitization of
      its Ca2+ response by fMLP and C5a, was equivalent to CXCR1. Regardless of the
      enhancement in certain receptor functions in M2CXCR1 compared with the wild type
      CXCR1, the mutated receptors mediated equivalent PLCbeta3 phosphorylation and
      cross-desensitization of Ca2+ mobilization by FR, C5aR, and PAFR. The results
      herein indicate that phosphorylation of CXCR1 regulates some, but not all of the
      receptors functions. While receptor phosphorylation inhibits G protein turnover,
      PLC activation, Ca2+ mobilization and secretion, it is required for normal
      chemotaxis and receptor internalization. Since phosphorylation of CXCR1 had no
      effect on its ability to induce phosphorylation of PLCbeta3 or to mediate class
      desensitization, these activities may be mediated by independently regulated
      pathways.

PMID- 9553133
TI  - Progesterone regulates transcription of the p21(WAF1) cyclin- dependent kinase
      inhibitor gene through Sp1 and CBP/p300.
AB  - Progesterone has biphasic effects on proliferation of breast cancer cells; it
      stimulates growth in the first cell cycle, then arrests cells at G1/S of the
      second cycle accompanied by up-regulation of the cyclin-dependent kinase
      inhibitor, p21. We now show that progesterone regulates transcription of the p21
      promoter by an unusual mechanism. This promoter lacks a canonical progesterone
      response element. Instead, progesterone receptors (PRs) interact with the
      promoter through the transcription factor Sp1 at the third and fourth of six Sp1
      binding sites located downstream of nucleotide 154. Mutation of Sp1 site 3
      eliminates basal transcription, and mutation of sites 3 and 4 eliminates
      transcriptional up-regulation by progesterone. Progesterone-mediated
      transcription is further prevented by overexpression of E1A, suggesting that
      CBP/p300 is required. Indeed, in HeLa cells, Sp1 and CBP/p300 associate with
      stably integrated flag-tagged PRs in a multiprotein complex. Since many signals
      converge on p21, cross-talk between PRs and other factors co-localized on the p21
      promoter, may explain how progesterone can be either proliferative or
      differentiative in different target cells.

PMID- 9553134
TI  - Cortactin-Src kinase signaling pathway is involved in N-syndecan-dependent
      neurite outgrowth.
AB  - N-syndecan (syndecan-3) was previously isolated as a cell surface receptor for
      heparin-binding growth-associated molecule (HB-GAM) and suggested to mediate the
      neurite growth-promoting signal from cell matrix-bound HB-GAM to the cytoskeleton
      of neurites. However, it is unclear whether N-syndecan would possess independent
      signaling capacity in neurite growth or in related cell differentiation
      phenomena. In the present study, we have transfected N18 neuroblastoma cells with
      a rat N-syndecan cDNA and show that N-syndecan transfection clearly enhances HB
      GAM-dependent neurite growth and that the transfected N-syndecan distributes to
      the growth cones and the filopodia of the neurites. The N-syndecan-dependent
      neurite outgrowth is inhibited by the tyrosine kinase inhibitors herbimycin A and
      PP1. Biochemical studies show that a kinase activity, together with its
      substrate(s), binds specifically to the cytosolic moiety of N-syndecan
      immobilized to an affinity column. Western blotting reveals both c-Src and Fyn in
      the active fractions. In addition, cortactin, tubulin, and a 30-kDa protein are
      identified in the kinase-active fractions that bind to the cytosolic moiety of N
      syndecan. Ligation of N-syndecan in the transfected cells by HB-GAM increases
      phosphorylation of c-Src and cortactin. We suggest that N-syndecan binds a
      protein complex containing Src family tyrosine kinases and their substrates and
      that N-syndecan acts as a neurite outgrowth receptor via the Src kinase-cortactin
      pathway.

PMID- 9553135
TI  - Regions remote from the site of cleavage determine macromolecular substrate
      recognition by the prothrombinase complex.
AB  - The proteolytic formation of thrombin is catalyzed by the prothrombinase complex
      of blood coagulation. The kinetics of prethrombin 2 cleavage was studied to
      delineate macromolecular substrate structures necessary for recognition at the
      exosite(s) of prothrombinase. The product, alpha-thrombin, was a linear
      competitive inhibitor of prethrombin 2 activation without significantly
      inhibiting peptidyl substrate cleavage by prothrombinase. Prethrombin 2 and alpha
      thrombin compete for binding to the exosite without restricting access to the
      active site of factor Xa within prothrombinase. Inhibition by alpha-thrombin was
      not altered by saturating concentrations of low molecular weight heparin.
      Furthermore, proteolytic removal of the fibrinogen recognition site in alpha
      thrombin only had a modest effect on its inhibitory properties. Both alpha
      thrombin and prethrombin 2 were cleaved with chymotrypsin at Trp148 and separated
      into component domains. The C-terminal-derived zeta2 fragment retained the
      ability to selectively inhibit macromolecular substrate cleavage by
      prothrombinase, while the zeta1 fragment was without effect. As the zeta2
      fragment lacks the fibrinogen recognition site, the P1-P3 residues or the intact
      cleavage site, specific recognition of the macromolecular substrate by the
      exosite in prothrombinase is achieved through substrate regions, distinct from
      the fibrinogen recognition or heparin-binding sites, and spatially removed from
      structures surrounding the scissile bond.

PMID- 9553136
TI  - Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important
      for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3
      to Il-2Rbeta.
AB  - Interleukin-2 (IL-2) induces heterodimerization of the IL-2 receptor beta (IL
      2Rbeta) and gammac chains of its receptor and activates the Janus family tyrosine
      kinases, Jak1 and Jak3. Whereas Jak1 associates with IL-2Rbeta, Jak3 associates
      primarily with gammac but also with IL-2Rbeta. We analyzed four IL-2Rbeta
      mutations that diminish IL-2-induced proliferation and found that each also
      decreased IL-2-induced signal transducer and activator of transcription (STAT)
      activation. For this reason, and because the mutations were in the IL-2Rbeta
      membrane-proximal region, we investigated and found that each mutation diminished
      IL-2Rbeta association with both Jak1 and Jak3. This suggested that these Jaks
      might interact with the same region of IL-2Rbeta; however, certain IL-2Rbeta
      internal deletions and C-terminal truncations differentially affected the
      association of Jak1 and Jak3. Interestingly, just as Jak1-IL-2Rbeta association
      is Jak3-independent and functionally important, we show that Jak3-IL-2Rbeta
      association is Jak1-independent and implicate this association as being important
      for IL-2-induced Stat5 activation. Moreover, Jak1 and Jak3 could associate only
      in the presence of IL-2Rbeta, suggesting that these kinases can simultaneously
      bind to IL-2Rbeta. Thus, our data not only demonstrate that somewhat more distal
      as well as membrane-proximal cytoplasmic regions of a type I cytokine receptor
      are important for Jak kinase association but also suggest that two IL-2Rbeta-Jak
      kinase interactions are important for IL-2 signaling.

PMID- 9553138
TI  - Multidrug resistance protein. Identification of regions required for active
      transport of leukotriene C4.
AB  - Multidrug resistance protein (MRP) is a broad specificity, primary active
      transporter of organic anion conjugates that confers a multidrug resistance
      phenotype when transfected into drug-sensitive cells. The protein was the first
      example of a subgroup of the ATP-binding cassette superfamily whose members have
      three membrane-spanning domains (MSDs) and two nucleotide binding domains. The
      role(s) of the third MSD of MRP and its related transporters is not known. To
      begin to address this question, we examined the ability of various MRP fragments,
      expressed individually and in combination, to transport the MRP substrate,
      leukotriene C4 (LTC4). We found that elimination of the entire NH2-terminal MSD
      or just the first putative transmembrane helix, or substitution of the MSD with
      the comparable region of the functionally and structurally related transporter,
      the canalicular multispecific organic anion transporter (cMOAT/MRP2), had little
      effect on protein accumulation in the membrane. However, all three modifications
      decreased LTC4 transport activity by at least 90%. Transport activity could be
      reconstituted by co-expression of the NH2-terminal MSD with a fragment
      corresponding to the remainder of the MRP molecule, but this required both the
      region encoding the transmembrane helices of the NH2-terminal MSD and the
      cytoplasmic region linking it to the next MSD. In contrast, a major part of the
      cytoplasmic region linking the NH2-proximal nucleotide binding domain of the
      protein to the COOH-proximal MSD was not required for active transport of LTC4.

PMID- 9553137
TI  - Characterization of insulin receptor substrate 4 in human embryonic kidney 293
      cells.
AB  - We recently cloned IRS-4, a new member of the insulin receptor substrate (IRS)
      family. In this study we have characterized IRS-4 in human embryonic kidney 293
      cells, where it was originally discovered. IRS-4 was the predominant insulin
      elicited phosphotyrosine protein in these cells. Subcellular fractionation
      revealed that about 50% of IRS-4 was located in cellular membranes, and
      immunofluorescence indicated that IRS-4 was concentrated at the plasma membrane.
      Immunoelectron microscopy conclusively established that a large portion of the
      IRS-4 was located at the cytoplasmic surface of the plasma membrane in both the
      unstimulated and insulin-treated states. IRS-4 was found to be associated with
      two src homology 2 (SH2) domain-containing proteins, phosphatidylinositol 3
      kinase and Grb2, the adaptor to the guanine nucleotide exchange factor for Ras.
      On the other hand, no significant association was detected with two other SH2
      domain proteins, the SH2-containing protein tyrosine phosphatase 2 and
      phospholipase Cgamma. Insulin-like growth factor I acting through its receptor
      was as effective as insulin in eliciting tyrosine phosphorylation of IRS-4, but
      interleukin 4 and epidermal growth factor were ineffective.

PMID- 9553139
TI  - A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid
      beta-peptide-binding protein involved in Alzheimer's disease.
AB  - A novel L-3-hydroxyacyl-CoA dehydrogenase from human brain has been cloned,
      expressed, purified, and characterized. This enzyme is a homotetramer with a
      molecular mass of 108 kDa. Its subunit consists of 261 amino acid residues and
      has structural features characteristic of short chain dehydrogenases. It was
      found that the amino acid sequence of this human brain enzyme is identical to
      that of an endoplasmic reticulum amyloid beta-peptide-binding protein (ERAB),
      which mediates neurotoxicity in Alzheimer's disease (Yan, S. D., Fu, J., Soto,
      C., Chen, X., Zhu, H., Al-Mohanna, F., Collison, K., Zhu, A., Stern, E., Saido,
      T., Tohyama, M., Ogawa, S., Roher, A., and Stern, D. (1997) Nature 389, 689-695).
      The purification of human brain short chain L-3-hydroxyacyl-CoA dehydrogenase
      made it possible to characterize the structural and catalytic properties of ERAB.
      This NAD+-dependent dehydrogenase catalyzes the reversible oxidation of L-3
      hydroxyacyl-CoAs to form 3-ketoacyl-CoAs, but it does not act on the D-isomers.
      The catalytic rate constant of the purified enzyme was estimated to be 37 s-1
      with apparent Km values of 89 and 20 microM for acetoacetyl-CoA and NADH,
      respectively. The activity ratio of this enzyme for substrates with chain lengths
      of C4, C8, and C16 was approximately 1:2:2. The human short chain L-3-hydroxyacyl
      CoA dehydrogenase gene is organized into six exons and five introns and maps to
      chromosome Xp11.2. The amino-terminal NAD-binding region of the dehydrogenase is
      encoded by the first three exons, whereas the other exons code for the carboxyl
      terminal substrate-binding region harboring putative catalytic residues. The
      results of this study lead to the conclusion that ERAB involved in neuronal
      dysfunction is encoded by the human short chain L-3-hydroxyacyl-CoA dehydrogenase
      gene.

PMID- 9553140
TI  - Transactivation of the human keratin 4 and Epstein-Barr virus ED-L2 promoters by
      gut-enriched Kruppel-like factor.
AB  - The Kruppel-like family of transcription factors comprises genes that appear to
      have tissue-restricted functions. Expression of gut-enriched Kruppel-like factor
      (GKLF) may be important in the switch from proliferation to differentiation in
      the squamous epithelium. We sought to determine transcriptionally mediated
      effects of GKLF on two promoters active in the esophageal squamous epithelium,
      namely the Epstein-Barr virus ED-L2 and human keratin 4 promoters. Both promoters
      contain a CACCC-like motif previously shown to bind GKLF. To determine whether
      GKLF regulates genes containing this element, we first demonstrated expression
      and then cloned the full-length human GKLF from an esophageal squamous carcinoma
      cell line. In a transient transfection system, GKLF increased the activity of
      both promoters >25-fold, localized to regions containing the CACCC-like element.
      Recombinant GKLF specifically binds the CACCC-like motif in both promoters. GKLF
      epitope-tagged protein leads to the formation of two proteins of 65 and 34 kDa.
      The chromatographically purified 65-kDa protein binds the CACCC-like element from
      both Epstein-Barr virus ED-L2 and keratin 4 promoters, which is not attenuated by
      the 34-kDa protein. In summary, GKLF is expressed in esophageal squamous
      epithelial cells and transcriptionally activates two esophageal epithelial
      promoters important at the transition toward differentiation.

PMID- 9553141
TI  - Visualization of dynamic trafficking of a protein kinase C betaII/green
      fluorescent protein conjugate reveals differences in G protein-coupled receptor
      activation and desensitization.
AB  - Protein kinase C (PKC) links various extracellular signals to intracellular
      responses and is activated by diverse intracellular factors including
      diacylglycerol, Ca2+, and arachidonic acid. In this study, using a fully
      functional green fluorescent protein conjugated PKCbetaII (GFP-PKCbetaII), we
      demonstrate a novel approach to study the dynamic redistribution of PKC in live
      cells in response to G protein-coupled receptor activation. Agonist-induced PKC
      translocation was rapid, transient, and selectively mediated by the activation of
      Gqalpha- but not Gsalpha- or Gialpha-coupled receptors. Interestingly, although
      the stimuli were continuously present, only one brief peak of PKC membrane
      translocation was observed, consistent with rapid desensitization of the
      signaling pathway. Moreover, when GFP-PKCbetaII was used to examine cross-talk
      between two Gqalpha-coupled receptors, angiotensin II type 1A receptor (AT1AR)
      and endothelin A receptor (ETAR), activation of ETARs resulted in a subsequent
      loss of AT1AR responsiveness, whereas stimulation of AT1ARs did not cause
      desensitization of the ETAR signaling. The development of GFP-PKCbetaII has
      allowed not only the real time visualization of the dynamic PKC trafficking in
      live cells in response to physiological stimuli but has also provided a direct
      and sensitive means in the assessment of activation and desensitization of
      receptors implicated in the phospholipase C signaling pathway.

PMID- 9553142
TI  - Mechanisms in the transcriptional regulation of bradykinin B1 receptor gene
      expression. Identification of a minimum cell-type specific enhancer.
AB  - To investigate the mechanisms of bradykinin B1 (BKB1) receptor gene expression,
      transient DNA transfection analyses of human BKB1 receptor gene promoter were
      performed in SV-40 transformed IMR90 cells. A positive regulatory element (PRE)
      located at position -604 to -448 base pair (bp) upstream of the transcription
      start site consistently exhibited, by far, the highest level of relative
      luciferase activity. A negative regulatory element, at position -682 to -604 bp,
      was able to completely ablate the function of the PRE. Transfection combined with
      deletion and mutation analyses illustrated that the PRE contains a classic,
      powerful enhancer. This enhancer was minimized to a 100-bp element at position 
      548 to -448 bp. A 78-bp fragment of negative regulatory element functioned as a
      silencer. Transient transfection of the enhancer construct, driven by
      heterologous herpes simplex thymidine kinase promoter, into a variety of cell
      types, showed that this enhancer presents a cell-type specific feature. In the
      characterization of the enhancer, motifs A (-548 to -532) and B (-483 to -477)
      were found to be essential for full enhancer activity. Motif D (-472 to -467)
      played a smaller role in enhancer activation. Gel shift and antibody supershift
      assays determined that an AP-1 factor binds with motif B. The nuclear protein
      which binds to motif A has yet to be identified. Both factors are the critical
      regulators for this enhancer activation.

PMID- 9553143
TI  - ZAP-70-dependent and -independent activation of Erk in Jurkat T cells.
      Differences in signaling induced by H2o2 and Cd3 cross-linking.
AB  - Oxidative stress in T cells induces signaling events similar to those initiated
      by T cell antigen receptor engagement, including tyrosine phosphorylation and
      activation of the critical protein-tyrosine kinase ZAP-70. Distal signaling
      events such as the activation of mitogen-activated protein kinases and downstream
      transcription factors are also initiated by oxidative stimuli. In this study
      P116, a ZAP-70-negative Jurkat T cell line, was used to investigate the role of
      ZAP-70 in mediating activation of Erk in response to H2O2. Consistent with the
      hypothesis that ZAP-70 is required for activation of Erk in response to an
      oxidative stimulus, Erk1 and Erk2 could be rapidly activated in Jurkat cells but
      not in P116 cells upon addition of H2O2. P116 cells became competent for H2O2
      induced Erk activation upon stable transfection with wild-type ZAP-70. An in vivo
      ZAP-70 substrate, SLP-76, implicated in Erk activation, also became rapidly
      tyrosine-phosphorylated in Jurkat cells, but not in P116 cells, upon treatment
      with H2O2. Surprisingly, although ZAP-70 was required for H2O2-mediated Erk
      activation, Erk activation in response to T cell antigen receptor engagement did
      not require ZAP-70. In addition to demonstrating a requirement for ZAP-70 in H2O2
      stimulated Erk activation, these results provide the first evidence for the
      existence of a ZAP-70-independent pathway for Erk activation in T cells.

PMID- 9553144
TI  - Bax in murine thymus is a soluble monomeric protein that displays differential
      detergent-induced conformations.
AB  - Bcl-2, Bcl-XL, and Bax are members of the Bcl-2 family that play important roles
      in apoptosis regulation. These proteins are believed to be membrane-bound and to
      regulate apoptosis through formation of homo- and heterodimers. However, we
      recently found by subcellular fractionation that whereas Bcl-2 is predominantly a
      membrane protein as previously reported, Bax and a significant fraction of Bcl-XL
      are soluble in thymocyte and splenocyte extracts. In addition, we have
      demonstrated that the ability of Bax to form dimers appears to be a detergent
      induced phenomenon that coincides with a detergent-induced conformational change.
      We have further investigated the tertiary and quaternary states of Bax in the
      presence of various detergents. Detergents such as Triton X-100 and Triton X-114
      readily enable Bax hetero- and homodimerization. However, other detergents such
      as polydocanol, W-1, octyl glucoside, dodecyl maltoside, Tween 20, and sodium
      cholate allow varying degrees of Bax hetero- and homodimerization. Detergents
      such as 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (Chaps) and
      Brij 35 allow neither hetero- nor homodimer formation. Immunoprecipitation
      analysis with the conformation-sensitive antibody uBax 6A7 revealed that whereas
      Triton X-100 readily exposes the N-terminal Bax epitope (amino acid 13-19), only
      limited exposure of the epitope occurs in Triton X-114, polydocanol, dodecyl
      maltoside, and sodium cholate, and no exposure of this epitope was observed in W
      1, Chaps, octyl glucoside, Tween 20, and Brij 35. Moreover, we could not detect
      any proteins associated with the cytosolic form of Bax based on
      immunopurification of this protein. Sephacryl S-100 gel filtration chromatography
      analysis of the cytosolic Bax indicated that this protein is monomeric and
      displays an apparent molecular mass of 25 kDa. Induction of apo-ptosis which
      causes the insertion of the soluble form of Bax into membranes did not result in
      appreciable Bax/Bcl-XL, Bax/Bcl-2 or Bax/Bax dimer formation as determined by
      cross-linking studies. Further analysis of Bax after apoptosis induction by
      immunoprecipitation in the presence of Chaps also revealed no significant
      heterodimer formation. In conclusion, Bax displays several distinct states in
      different detergents that expose defined regions of the protein. In addition,
      these results suggest that mechanisms other than the simple dimerization among
      members of the Bcl-2 family may be required for the regulation of apoptosis.

PMID- 9553145
TI  - Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a
      repressor of C/EBPbeta-mediated gene activation.
AB  - Transcription factor C/EBPbeta has been known to regulate a wide array of genes
      including those involved in the acute-phase response. One of the molecular
      mechanisms underlying transcription activation by C/EBPbeta is through protein
      protein interaction with other transcription factors. Here we report the
      identification and characterization of physical and functional interactions
      between C/EBPbeta and heterogeneous nuclear ribonucleoprotein (hnRNP) K. This
      interaction results in the repression of C/EBPbeta-dependent trans-activation of
      the agp gene. Footprinting assays indicate that hnRNP K cannot bind to the
      promoter region of agp gene or interfere with the binding of C/EBPbeta to its
      cognate DNA site. Furthermore, agp gene activation by the synergistic interaction
      of Nopp140 and C/EBPbeta is abolished by hnRNP K. The kinetics of appearance of
      C/EBPbeta-hnRNP K complex in the nuclear extract after initiation of acute-phase
      reaction indicates that hnRNP K functions as a negative regulator of C/EBPbeta
      mediated activation of agp gene.

PMID- 9553146
TI  - The activation of p38 and apoptosis by the inhibition of Erk is antagonized by
      the phosphoinositide 3-kinase/Akt pathway.
AB  - Considerable attention has recently been focused on the role played by different
      kinase cascades in the control of apoptosis. The triggering of stress-activated
      kinases concomitant with the inhibition of the extracellular signal-regulated
      kinase (ERK) pathway has been observed in a number of cell systems undergoing
      programmed cell death. In addition, the activation of the phosphoinositide 3
      kinase (PI 3-kinase)-Akt signaling cascade has been shown to protect from
      apoptosis. Here we have explored the potential role played by the inhibition of
      ERK in the activation of the stress kinases as well as the possible cross-talk
      with the PI 3-kinase pathway in HeLa cells. We show that the simple inhibition of
      ERK basal activity is sufficient to trigger apoptosis and p38 activation with no
      changes in Jun N-terminal kinase/stress-activated protein kinase. This is a
      process dependent on the caspases and is completely abrogated by serum. The
      incubation with wortmannin or the transfection of dominant negative mutants of
      p85 or Akt block the inhibitory function of serum, suggesting the involvement of
      the PI 3-kinase-Akt system. Consistent with this, expression of active mutants of
      PI 3-kinase and Akt inhibits p38 activation and apoptosis. We also show here that
      the inhibition of ERK triggers the caspase system, which is abolished by serum in
      a wortmannin-dependent manner. Collectively, these results demonstrate a link
      between ERK and the p38 apoptotic pathway that is modulated by the survival PI 3
      kinase-Akt module, acting upstream the caspase system.

PMID- 9553147
TI  - Identification and characterization of two distinct truncated forms of gp130 and
      a soluble form of leukemia inhibitory factor receptor alpha-chain in normal human
      urine and plasma.
AB  - Leukemia inhibitory factor (LIF) is a polyfunctional cytokine known to require at
      least two distinct receptor components (LIF receptor alpha-chain and gp130) in
      order to form a high affinity, functional receptor complex. In this report, we
      present evidence that there are two distinct truncated forms of gp130 in normal
      human urine and plasma: a large form with a molecular weight of approximately
      100, 000, which is similar to a previously described form of soluble gp130 in
      human serum, and a previously undescribed small form with a molecular weight of
      approximately 50,000. Using a panel of monoclonal antibodies raised against the
      extracellular domain of human gp130, we were able to show that the small form of
      the urinary gp130 probably contained only the hemopoietin domain. Both forms of
      gp130 bound LIF specifically and were capable of forming heterotrimeric complexes
      with soluble human LIF receptor alpha-chain in the presence of human LIF. In
      addition to the soluble forms of gp130, a soluble form of LIF receptor alpha
      chain was also detected in human urine and plasma.

PMID- 9553148
TI  - Evolutionary history and mechanism of the Drosophila cecropin gene family.
AB  - Upon bacterial infection, insects secrete a set of synthesized antibacterial
      proteins into the hemolymph and initiate synergistic destruction of invaders.
      Cecropin is one such antibacterial protein which is also found in vertebrates. To
      study the evolutionary history and mechanism of the Cecropin gene family, we
      determined DNA sequences of one isogenic In(3R)C and six isofemale lines of
      Drosophila melanogaster as well as one line of D. simulans and of D. yakuba. The
      phylogenetic analysis of these sequences together with those published for D.
      virilis and Sarcophaga peregrina reveals frequent gene re-organization. It was
      also found that silent nucleotide differences within D. melanogaster are quite
      heterogeneous across the gene region of approximately 3 kilobases and the extent
      of polymorphism is unusually usually high. These data suggest that the Cecropin
      gene region of D. melanogaster underwent intragenic recombination as well as
      introgression from a closely related sibling species, D. simulans.

PMID- 9553149
TI  - Footprints of intragenic recombination at HLA loci.
AB  - To evaluate the effect of balancing selection and intragenic recombination (or
      gene conversion) at six individual HLA loci, synonymous nucleotide diversity in
      different exon groups is examined within (pi w) and between (pi b) allelic
      lineages that may be defined by either serological or DNA sequence differences.
      Both pi values are high in exons which encode for the peptide binding region
      (PBR) and tend to decrease in other exons. The value of pi w is significantly
      smaller than that of pib in any exon of any locus. However, even pi w is much
      greater than nucleotide diversity at non-HLA loci. These observations provide
      additional strong evidence for the operation of balancing selection in PBR
      encoding exons and its indirect effects on polymorphism at linked neighboring
      regions. It appears that allelic lineages have generally evolved in isolation but
      the linkage relationships within and between exons are incomplete throughout the
      long evolutionary history. To quantify intragenic recombination and account for
      the large discrepancy between the HLA and non-HLA diversity, a population
      genetics model is analyzed with special reference to the evolution of modern
      humans. The analysis suggests that the recombination rate between two sites 1000
      base pairs apart is about 10(-5) per generation and that the effective size of
      human populations (equivalent roughly to the number of breeding individuals in a
      randomly mating population) has dropped from 10(5) to 10(4) in most of the
      Quaternary. One possibility for this reduction is discussed.

PMID- 9553151
TI  - HLA-DRB1*03, but not the TNFA -308 promoter gene polymorphism, confers protection
      against fistulising Crohn's disease.
AB  - Crohn's disease (CD) appears in forms so diverse that it has been hypothesized CD
      might be a syndrome, with different pathogenic mechanisms leading to the various
      clinical phenotypes. This may plausibly explain the conflicting and inconclusive
      results with regard to HLA associations in unselected groups of patients. The
      power of these association studies may increase when disease heterogeneity is
      taken into account. As fistulising CD has been proposed as a separate subgroup of
      patients with CD, we studied the carrier frequencies (CF) of the DRB1 alleles in
      35 unrelated Caucasian Dutch CD patients with proven peri-anal fistulas. A
      striking decrease in the frequency of the DRB1(*)03 allele was found in those
      patients with peri-anal fistulas when compared with a panel of 2400 healthy
      controls (HC) (3% vs 25%; P = 0.005; Odds Ratio [OR] = 0.09). The DRB1(*)03
      allele is in strong linkage disequilibrium with a polymorphism at position -308
      in the promoter region of the gene encoding TNFalpha (TNFA-308(*)2). We
      investigated whether this allele frequency was decreased as well. Surprisingly,
      the CF of TNFA-308(*)2 was 29%, not different from the CF of 98 HC (34%; P = 0.
      7; OR = 0.8). This study is the first showing a significant negative association
      between DRB1(*)03 and a particular subgroup of CD patients. Thus, patient
      selection may largely determine the outcome of genetic association studies in CD,
      as we previously observed no association with this allele in an unselected
      population of CD patients. As DRB1(*)03 frequency, but not the closely linked
      TNFA-308(*)2, was decreased, this suggests recombination between the DRB1 and
      TNFA loci in this group of patients, and may help to define the biological basis
      of fistula formation.

PMID- 9553150
TI  - cDNA cloning of human DEC-205, a putative antigen-uptake receptor on dendritic
      cells.
AB  - Dendritic cells (DC) are specialist antigen presenting cells which capture
      antigens in the periphery, migrate centrally, and present the processed antigens
      in the context of major histocompatibility complex and appropriate co-stimulatory
      molecules to T lymphocytes for the initiation of an immune response. DEC-205 has
      been identified as a putative antigen-uptake receptor, which is expressed
      abundantly on mouse DC. The recently cloned mouse DEC-205 cDNA predicts a
      molecular structure which has a marked similarity to the macrophage mannose
      receptor. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and cDNA
      library screening, we obtained the full coding region of human DEC-205 cDNA from
      the Hodgkin's disease-derived L428 cell line. The predicted protein structure is
      a type I transmembrane protein of 1722 amino acids consisting of a signal
      peptide, cysteine-rich domain, fibronectin type II domain, ten carbohydrate
      recognition-like domains, transmembrane domain, and a cytoplasmic tail. Human DEC
      205 is 77% identical to the mouse protein with completely conserved cysteines.
      The DEC-205 gene (LY75) was mapped to chromosome band 2q24 by somatic cell hybrid
      panel analysis and fluorescent in situ hybridization. Northern blot analysis
      detected 7.8 and 9.5 kilobase DEC-205 transcripts in myeloid, B lymphoid, and
      Hodgkin's disease-derived cell lines. RT-PCR analysis indicated that immature
      blood DC contain a barely detectable amount of DEC-205 transcripts but these were
      markedly increased upon differentiation/activation.

PMID- 9553152
TI  - Analysis of polymorphisms in the major expressed class I locus (B-FIV) of the
      chicken.
AB  - We analyzed the polymorphic nature of eleven alleles expressed by the major class
      I locus (B-FIV) in chickens. Similar to mammalian class I loci, the nucleotide
      substitutions with high variability occur in exons 2 and 3 encoding the alpha1
      and alpha2 domains. However, the nonsynonymous to synonymous ratio of nucleotide
      substitutions in exon 3 encoding the alpha helix and beta sheets is reversed
      compared with HLA. The region of exon 3 encoding the alpha2 helix demonstrates a
      much lower nonsynonymous to synonymous ratio, suggesting evolutionary selection
      of a more conserved alpha2 helix in B-FIV compared with HLA. Amino acid residues
      with high Wu-Kabat variability are typically located in positions predicted to
      impact antigen presentation. B-FIV amino acid residues predicted to interact with
      the CDR1alpha region of the T-cell receptor (Tcr) demonstrate less variability
      than in mouse and human class I alleles. The combination of a reduced
      nonsynonymous to synonymous ratio in exon 3 encoding the alpha2 helix and the
      limited variability in CDR1alpha contact residues is discussed with regard to
      concerted evolution between a minimal major histocompatibility complex and
      compaction of Tcr variable gene segments in the chicken.

PMID- 9553153
TI  - Linkage analysis of HSP70 genes and historecognition locus in botryllus
      schlosseri.
AB  - The protochordate allorecognition system has long invited comparison with the
      vertebrate major histocompatibility complex (MHC). In the colonial species
      Botryllus schlosseri, a rapid fusion or rejection response resembling graft
      acceptance or rejection in vertebrates is controlled by a single highly
      polymorphic genetic region. Because linkage between heat shock protein 70 (HSP70)
      genes and the MHC appears to be conserved within the vertebrate lineage, linkage
      relationships between two HSP70 genes (HSP70.1 and HSP70.2) and the
      historecognition locus (FuHC) have been analyzed in B. schlosseri. Segregation
      patterns of restriction fragment length polymorphisms located in the 3' flanking
      regions of HSP70.1 and HSP70.2 were determined for progeny of defined crosses.
      These progeny were also analyzed for fusibility type by an in vivo cut colony
      assay. No close linkage was detected between any of the three loci. These results
      do not support the hypothesis that the allorecognition response in B. schlosseri
      is determined by an MHC homologue. However, it remains a possibility that
      orthologues of other MHC-linked genes will be linked to the B. schlosseri FuHC.

PMID- 9553154
TI  - Isolation and molecular characterization of the rat MR1 homologue, a non-MHC
      linked class I-related gene.
AB  - We isolated and analyzed a new rat gene which is homologous to the recently
      described human major histocompatibility complex class I-related gene MR1. The
      deduced amino acid sequence of the rat Mr1 gene shows conserved cysteine residues
      typical of class I genes as well as conserved beta2-microglobulin and CD8 contact
      sites. Analysis of partial DNA sequences and restriction fragment length
      polymorphism patterns of several inbred rat strains indicate that Mr1 is not
      polymorphic. Mr1 is a single-copy gene, which could be mapped to rat chromosome
      13 by co-segregation analysis of Mr1 and a microsatellite marker in the renin
      (Ren) gene in double-backcross hybrids. The recombination frequency between both
      genes was determined to be 14.7% (4.9-31.1, 95% confidence limits). Expression
      analysis revealed various Mr1 transcripts in each organ tested and occurrence of
      alternative splicing.

PMID- 9553155
TI  - Opossum (Monodelphis domestica) terminal deoxynucleotidyl transferase gene.

PMID- 9553156
TI  - Polymorphism and multiple loci for the horse DQA gene.

PMID- 9553157
TI  - HTEX4, a new human gene in the MHC class I region, undergoes alternative splicing
      and polyadenylation processes in testis.

PMID- 9553158
TI  - Polymorphism of the tumor necrosis factor A gene in Melanesian and East-Asian
      populations.

PMID- 9553159
TI  - A polymorphic dinucleotide repeat in the 5' flanking region of the human
      interleukin 11 (IL11) gene.

PMID- 9553160
TI  - Complete coding sequence of a serologically undefined HLA-B antigen: HLA-B*1537.

PMID- 9553161
TI  - Characterization of 12 microsatellite loci of the human MHC in a panel of
      reference cell lines 

PMID- 9553162
TI  - [carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is a potent and selective radioligand
      for central 5-HT1A receptors in vitro and in vivo.
AB  - [carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is possibly a low-level metabolite
      appearing in plasma after intravenous administration of [carbonyl-11C]WAY-100635
      to human subjects for positron emission tomographic (PET) imaging of brain 5-HT1A
      receptors. In this study we set out to assess the ability of DWAY to enter brain
      in vivo and to elucidate its possible interaction with 5-HT1A receptors.
      Desmethyl-WAY-100635 was labelled efficiently with carbon-11 (t1/2 = 20.4 min) in
      high specific radioactivity by reaction of its descyclohexanecarbonyl analogue
      with [carbonyl-11C]cyclohexanecarbonyl chloride. The product was separated in
      high radiochemical purity by high-performance liquid chromatography (HPLC) and
      formulated for intravenous injection. Rats were injected intravenously with DWAY,
      sacrificed at known times and dissected to establish radioactivity content in
      brain tissues. At 60 min after injection, the ratios of radioactivity
      concentration in each brain region to that in cerebellum correlated with previous
      in vitro and in vivo measures of 5-HT1A receptor density. The highest ratio was
      about 22 in hippocampus. Radioactivity cleared rapidly from plasma; HPLC analysis
      revealed that DWAY represented 55% of the radioactivity in plasma at 5 min and
      33% at 30 min. Only polar radioactive metabolites were detected. Subsequently, a
      cynomolgus monkey was injected intravenously with DWAY and examined by PET.
      Maximal whole brain uptake of radioactivity was 5.7% of the administered dose at
      5 min after injection. The image acquired between 9 and 90 min showed high
      radioactivity uptake in brain regions rich in 5-HT1A receptors (e.g. frontal
      cortex and neocortex), moderate uptake in raphe nuclei and low uptake in
      cerebellum. A transient equilibrium was achieved in cortical regions at about 60
      min, when the ratio of radioactivity concentration in frontal cortex to that in
      cerebellum reached 6. The corresponding ratio for raphe nuclei was about 3.
      Radioactive metabolites appeared rapidly in plasma, but these were all more polar
      than DWAY, which represented 52% of the radioactivity in plasma at 4 min and 20%
      at 55 min. In a second PET experiment, in which a cynomolgus monkey was
      pretreated with the selective 5-HT1A receptor antagonist, WAY-100635, at 25 min
      before DWAY injection, radioactivity in all brain regions was reduced to that in
      cerebellum. Autoradiography of post mortem human brain cryosections after
      incubation with DWAY successfully delineated 5-HT1A receptor distribution.
      Receptor-specific binding was eliminated in the presence of the selective 5-HT1A
      receptor agonist, 8-OH-DPAT [(+/-)-8-hydroxy-2-dipropylaminotetralin]. These
      findings show that: (a) intravenously administered DWAY is well able to penetrate
      brain in rat and monkey, (b) DWAY is a highly effective radioligand for brain 5
      HT1A receptors in rat and monkey in vivo and for human brain in vitro, and (c)
      the metabolism and kinetics of DWAY appear favourable to successful
      biomathematical modelling of acquired PET data. Thus, DWAY warrants further
      evaluation as a radioligand for PET studies of 5-HT1A receptors in human brain.

PMID- 9553164
TI  - Technetium-99m Q4: a prototype cationic perfusion radiotracer with myocardial
      washout.
AB  - Technetium-99m Q4 is derived from an existing mixed ligand myocardial tracer
      (99mTc-Q3) by the addition of an ester group to promote myocardial washout. Six
      subjects with single-vessel coronary disease documented by angiography and/or Q
      wave myocardial infarction documented by electrocardiography were studied with
      99mTc-Q4 injection during exercise and with comparative thallium-201 tomography.
      Six healthy volunteers were also studied with 99mTc-Q4 imaging following
      injection at peak exercise. Tomographic images with 99mTc-Q4 and 201Tl each
      provided correct assessment of the presence or absence of coronary disease in 22
      of 30 myocardial segments (73.3%). Six myocardial segments showed defect
      reversibility with 99mTc-Q4, whereas 14 segments showed reversibility with 201Tl,
      but the latter included three segments with no angiographic or
      electrocardiographic evidence of disease. In both normals and subjects with
      coronary artery disease, significant global washout of 99mTc-Q4 was observed over
      4 h. For five patients with angiographic evidence of unrevascularized coronary
      artery stenosis, the ischemic to normal zone count ratio increased from 0. 782+/
      0.107 at 45 min postexercise to 0.891+/-0.115 at 4 h postexercise (P = 0.016),
      suggesting occurrence of differential washout. It is concluded that addition of
      an ester group functionality to a previously studied mixed ligand cardiac tracer
      promotes global and regional myocardial tracer washout. Nevertheless,
      demonstration of perfusion defect reversibility with comparable frequency to that
      observed with 201Tl stress and reinjection images, required separate injections
      of 99mTc-Q4 at peak stress and at rest.

PMID- 9553163
TI  - Imaging of infection in rabbits with radioiodinated interleukin-1 (alpha and
      beta), its receptor antagonist and a chemotactic peptide: a comparative study.
AB  - Previous studies have reported the favourable characteristics of chemotactic
      peptides and interleukins for imaging of infection and inflammation. In the
      present study, the potential of two species of interleukin 1 (IL-1), IL-1alpha
      and IL-1beta, the IL-1 receptor antagonist (IL-1ra) and the synthetic chemotactic
      peptide N-formyl-methionyl-leucyl-phenylalanyl-lysine (fMLFK) were directly
      compared in a rabbit model of infection. IL-1alpha, IL-1beta, IL-1ra and fMLFK
      were labelled with iodine-123 according to the Bolton-Hunter method. Twenty-four
      hours after induction of Escherichia coli abscesses in the left thigh muscle,
      rabbits were injected intravenously with 0.5 mCi of 123I-labelled agent. Gamma
      camera images were obtained at 5 min and 1, 4, 8 and 20 h p.i. Biodistribution
      was determined at 20 h p.i. Although all agents rapidly cleared from the blood,
      at 20 h p.i. blood levels and the levels in most organs of 123I-fMLFK were
      significantly lower than those of the other three agents (P<0.05). The abscesses
      were clearly visualized with all agents from 4 h p.i. onwards. After 1 h p.i.,
      the abscess uptake of 123I-IL-1beta was significantly higher than that of the
      other agents (P<0.05), with the highest uptake observed at 8 h p.i. (1.3%+/
      0.3%). After 20 h p.i., the highest abscess-to-contralateral muscle ratios were
      obtained with 123I-IL-1beta, i.e. 39.0+/-11.5 vs 18.7+/-5.4, 18.1+/-2.3 and 29.
      9+/-7.0 for 123I-IL-1alpha, 123I-IL-1ra and 123I-fMLFK, respectively. In
      conclusion, all agents localized in the infectious focus. The potential of
      radiolabelled IL-1beta for imaging of infection was better than that of the other
      agents: higher absolute uptake in the infection and higher abscess-to
      contralateral muscle ratios were obtained. The observation of localization of
      radiolabelled IL-1ra in infection was important since this protein can be
      administered to humans without any side-effects.

PMID- 9553165
TI  - Assessment of reperfused myocardium using a new ischaemia-avid imaging agent,
      technetium-99m HL91: comparison with myocardial glucose uptake.
AB  - We evaluated the efficacy of a new ischae-mia-avid imaging agent, technetium-99m
      labelled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (99mTc- HL91)
      as a marker of myocardial viability in ischaemic and reperfused myocardium. The
      left coronary artery of rats was ligated for 15 or 60 min and released. The
      myocardium was reperfused for 60 min [stunned myocardium, or acute myocardial
      infarction (MI)] or 7 days (subacute MI). Thereafter, 99mTc-HL91 and carbon-14 2
      deoxyglucose (DG) were co-injected 30 min before sacrifice. We evaluated the
      myocardial accumulation of 99mTc-HL91 and DG by dual-tracer ex vivo
      autoradiography. The uptake of each tracer in the myocardial region was
      normalized by that in the septum (control), and expressed as percent uptake (%HL
      or %DG, respectively). Individual hearts were also histopathologically examined.
      The %HL in the stunned myocardium (n = 8) and in the septum were identical
      (101%+/-15%, mean+/-SD, P = ns), whereas the %DG was significantly increased
      (149%+/-27%, P<0.05) compared with that in the septum. These results suggest that
      99mTc-HL91 cannot visualize stunned myocardium, whereas DG can. In acute MI (n =
      7), the %HL (423%+/-96%, P<0.005) and the %DG (318%+/-91%, P<0.001) in the non
      infarcted area at risk were significantly augmented compared with those in the
      septum. The %DG (181%+/-17%) in the infarcted area was also augmented (P<0.001),
      whereas the %HL (106%+/-25%) in the infarcted area was identical to that in the
      septum (P = ns). These results indicate that 99mTc-HL91 detected viable
      myocardium in the area at risk. In subacute MI (n = 8), the%HL in the infarcted
      area (101%+/-45%) and in the septum was identical, whereas %DG (292%+/-57%) was
      significantly higher than that in the non-infarcted risk area or the septum
      (P<0.0001). These findings suggest that DG detected viable myocardium in the area
      at risk, but that 99mTc-HL91 was not retained. We conclude that 99mTc-HL91 is a
      potent marker of myocardial viability when used during the early acute phase
      after reperfusion.

PMID- 9553167
TI  - Scintimammography with technetium-99m methoxyisobutylisonitrile: results of a
      prospective European multicentre trial.
AB  - The aim of the trial was to determine the diagnostic accuracy of
      scintimmammography with technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) in
      the detection of primary breast cancer and to verify its clinical usefulness. A
      total of 246 patients with a suspicious breast mass or positive mammogram were
      included in this prospective European multicentre trial. At 5 min and 60 min
      (optional) p.i. two lateral prone images were acquired for 10 min each; 30 min
      p.i. one anterior image was acquired for 10 min. There were 253 lesions (195
      palpable and 58 non-palpable), in respect of which histology revealed 165 cancers
      and 88 benign lesions. Institutional and blinded read results were correlated to
      core laboratory histopathology results obtained during excisional biopsy.
      Diagnostic accuracy for the detection of breast cancer was calculated per lesion.
      The overall sensitivity and specificity of blinded read scintimammography were
      71% and 69%, respectively. For palpable lesions, the sensitivity of blinded read
      and institutional read scintimammography was 83% and 91%, respectively.
      Sensitivity was not dependent on the density of the breast tissue. Invasive
      ductal and invasive lobular cancers showed similar sensitivity. The sensitivity
      and specificity of mammography were 91% and 42%, respectively, and did not depend
      on the tumour size. In 60% of false-negative mammograms, 99mTc-MIBI was able to
      diagnose malignancy (true-positive). High-quality imaging with 99mTc-MIBI has a
      high diagnostic accuracy for the detection of primary breast cancer. Used as a
      complementary method, scintimammography with 99mTc-MIBI can help to diagnose
      breast cancer at an earlier stage in patients with dense breasts.

PMID- 9553166
TI  - The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an
      increase in salt iodization in 1990.
AB  - Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre
      with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary
      iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in
      adults remained in the endemic range of 15%-30%. Therefore salt iodization was
      doubled in 1990. The aim of this study was to assess the annual incidence of
      different types of hyperthyroidism (HT) before and after this increase in salt
      iodization. The incidence of HT was recorded in 14 nuclear medicine centres from
      1987 to 1995. In five additional centres data were available from 1992 onwards.
      Data prior to 1992 were documented retrospectively, while those after 1992 were
      recorded prospectively. The 14 centres drew patients from an area with a
      population of approximately 4.23 million while all 19 institutes were estimated
      to cover an area with a population of 5.4 million (the total population of
      Austria is 7.86 million). A total of 414232 persons were examined for the first
      time in the participating centres. HT and the type of HT were defined by clinical
      examination, serum TSH, thyroid hormone levels in blood, ultrasonography,
      scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT
      (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-,
      multinodular or disseminated Plummers' disease, PD). HT was also divided into
      overt (o) or subclinical (sc) disease. The following data were calculated: annual
      incidence per 100000 and the relative risk (RR) for HT with 95% confidence
      intervals (CI). In addition, linear trends were calculated for each type of HT by
      means of logistic regressions. In the 19 centres a total of 47834 patients with
      HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and
      GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time
      period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000.
      The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45)
      and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was
      27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was
      1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons
      older than 50 years of age, particularly in men. The incidence of oGD in T0 was
      10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993
      and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6
      2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still
      2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly
      distributed in all ages and both sexes. The time course of different types of HT
      following the increase in salt iodization could be divided into two phases: an
      increase in the incidences of HT with peaks after 1-4 years and a subsequent
      decrease, the only exception being scGD. The effect was more pronounced in GD
      than in PD. PD showed an age and gender dependency over time, while GD did not.

PMID- 9553168
TI  - Intraindividual comparison of 99mTc-labelled anti-SSEA-1 antigranulocyte antibody
      and 99mTc-HMPAO labelled white blood cells for the imaging of infection.
AB  - Technetium-99m labelled antigranulocyte antibodies are ready to use and are
      sensitive and specific in the diagnosis of infectious diseases. 99mTc-SSEA
      antigranulocyte antibodies have a very high affinity constant (Kd 10(-12) M) for
      human neutrophils (PMNs), and excellent imaging qualities with high
      target/background ratios. The aim of this study was to compare the diagnostic
      accuracy of the 99mTc-anti-SSEA-1 monoclonal antibody (Mab) with that of 99mTc
      hexamethylpropylene amine oxime (HMPAO)-labelled white blood cells (WBCs). To
      this end, 17 patients with 23 proven infectious foci were examined with 555 MBq
      99mTc-anti-SSEA-1 MAb and with 370 MBq 99mTc-HMPAO labelled autologous leucocytes
      within a period of 7 days. All the infections were confirmed by culture, biopsy,
      surgery and follow-up. Whole-body images and planar spot views with the antibody
      were performed at 1-h, 4-h and 24-h post injection; the biodistribution of the
      antibody was quantified, absorbed radiation doses were calculated and the
      diagnostic results were compared with the 99mTc-HMPAO WBC images. Human anti
      mouse antibody (HAMA) evaluation was performed in all patients before and 3
      months after antibody injection. Blood was drawn at different times after 99mTc
      anti-SSEA-1 MAb injection to determine the amount of granulocyte-associated
      radioactivity and to calculate recovery. 99mTc-anti-SSEA-1 MAb scintigraphy
      detected all 23 lesions, while 21 were detected with 99mTc-HMPAO WBC scan. In
      this small group of patients, the sensitivity and specificity of 99mTc-anti-SSEA
      1 MAb scintigraphy were 95% and 96% respectively, as compared with 91% and 82%
      respectively for 99mTc-HMPAO WBC scan. An increasing uptake of the injected
      activity in the lesion at different time points was indicative of high affinity
      and of specific PMN binding. There was no HAMA formation. In four of five
      patients investigated, a transient mild leukopenia was found at 15 min p.i..
      There was increased uptake of the antibody in liver and spleen and normal uptake
      in kidneys and bone marrow. The estimated radiation doses for the whole body and
      the red bone marrow were 1.1x10(-2) cGy/37 MBq and 5.3x10(-2) cGy/37 MBq,
      respectively. The activity associated to the PMNs in vivo was 33.5%, 30.6%, 21.3%
      and 9% at 5, 15, 30 and 45 min. post-injection, respectively. It is councluded
      that use of 99mTc-anti-SSEA-1 antigranulocyte antibodies demonstrates promising
      results comparable to those obtained with 99mTc-labelled autologous WBCs. The
      99mTc-labelled MAb is ready to use, has excellent image qualities and a high
      target/background ratio.

PMID- 9553169
TI  - A comparison of adenosine and arbutamine for myocardial perfusion imaging.
AB  - We have compared our standard stress protocol (adenosine combined with exercise)
      with the new stress agent arbutamine, for thallium-201 myocardial perfusion
      imaging (MPI) in order to assess the comparative value of arbutamine. We studied
      23 patients referred for MPI, and each patient had two studies (18 males, median
      age 66 years, five with previous myocardial infarction). Uptake scores were
      assigned to each of nine segments, and the extent and severity of defects were
      measured using a polar plot. Haemodynamic changes were greater with arbutamine
      (rate-pressure product increase 78% vs 51%, P = 0.003). Symptoms were experienced
      by 21 patients with arbutamine and 16 with adenosine (P = 0.07). Agreement
      between the techniques for classification of patients as normal or as having
      reversible, fixed or mixed defects was good (19 of 23 studies, 83%, kappa =
      0.76). Agreement for similar classification of segments was also good (82%, kappa
      = 0.71). Segmental agreement for stress scores was good (86%, kappa = 0.77).
      However, mean size of stress defect was larger with adenosine (83+/-52 pixels vs
      65+/-48 pixels, P<0.05), though severity and reversibility were similar (P = NS).
      We conclude that arbutamine provides comparable results to those obtained with
      adenosine and exercise and that the observed differences are not clinically
      significant.

PMID- 9553170
TI  - Application of SPET using technetium-99m sestamibi in brain tumours and
      comparison with expression of the MDR-1 gene: is it possible to predict the
      response to chemotherapy in patients with gliomas by means of 99mTc-sestamibi
      SPET?
AB  - Technetium-99m sestamibi (MIBI) is thought to be passively taken up by
      metabolically active tumour cells and effluxed from them by P-glycoprotein (Pgp).
      This 170-kDa membrane-bound protein, encoded by the MDR-1 gene, acts as an energy
      dependent efflux pump for several antineoplastic agents, resulting in multidrug
      resistance. For this reason, it is of interest whether the tumour's response to
      chemotherapy can be predicted by MIBI single-photon emission tomography (SPET).
      In this study, MIBI SPET was compared with thallium-201 (Tl) SPET using magnetic
      resonance imaging as a guide in 16 patients with untreated brain tumours [ten
      glioblastomas (GBs), two anaplastic astrocytomas (AAs), two low-grade gliomas
      (LGASs) and two metastatic brain tumours) and in four patients who had received
      treatment for with brain tumours (two GBs, two AAs). In addition, we investigated
      the expression of the MDR-1 gene and its product Pgp in the same patients, and
      compared the results with MIBI SPET findings. MIBI, as well as Tl, was highly
      accumulated and retained in the enhanced region of malignant gliomas. In
      addition, MIBI SPET yielded sharp and well-contrasted images, and the margin of
      the tumour was more clearly defined than with Tl SPET due to a good signal-to
      noise ratio. Follow-up MIBI SPET in patients who had received therapy showed
      marked uptake in a patient with malignant transformation, who deteriorated
      clinically. Patients with no uptake on MIBI SPET showed no sign of recurrence.
      Semiquantitative analysis of untreated patients showed a relationship between the
      early uptake index (UI, ratio of average count/pixel in the lesion to that in the
      contralateral area on early images) and the degree of malignancy (early UI =
      1.08+/-0.06 in LGASs, 4.10+/-0.84 in AAs, 5.71+/-3.47 in GBs, and 7.52+/-1.52 in
      metastatic brain tumours). The retention index (RI, ratio of delayed to early UI)
      of MIBI was significantly lower than that of Tl in metastatic brain tumours
      (P<0.05), but not in malignant gliomas. Histological and biological investigation
      of gliomas showed that the MDR-1 gene and its product Pgp were expressed only in
      normal endothelial cells and not in tumour cells or proliferating endothelial
      cells; Pgp tended to decrease as the degree of malignancy rose. Hence, the
      presence of Pgp and the grade of malignancy were inversely related in gliomas. By
      contrast, immunohistochemical study showed strong accumulation of Pgp in
      metastatic brain tumour cells. These histopathological findings and MIBI SPET
      findings are compatible with experimental data; MIBI was washed out by Pgp. The
      main cause of chemoresistance is probably not an increasing drug efflux by Pgp in
      gliomas. Thus, MIBI SPET is useful for detecting the active lesions, but may not
      be useful for predicting the response to chemotherapy in gliomas.

PMID- 9553171
TI  - Preliminary application of dynamic pulmonary xenon-133 single-photon emission
      tomography in the evaluation of patients with pulmonary emphysema for
      thoracoscopic lung volume reduction surgery.
AB  - Dynamic pulmonary xenon-133 single-photon emission tomography (SPET) with three
      dimensional (3D) displays was preliminarily applied to select resection targets
      for thoracoscopic lung volume reduction surgery (LVRS) and to assess regional
      ventilatory changes following surgery. Dynamic SPET was performed using a triple
      detector SPET system in 14 patients with pulmonary emphysema before and after
      LVRS. After reconstructing colour-illuminated, surface-rendered 3D images of
      equilibrium (EQ) and 3-min washout (WO3), a single 3D fusion display was created
      from these two different time-course image sets, in which the 3D WO3 image
      indicating 133Xe retention was visible through the overlying 3D EQ image
      delineating lung contours. Volumetric extent of retention on this display was
      quantified by a 133Xe retention index, defined as the ratio (%) of total pixel
      numbers of segmented 3-min WO data to those of EQ data. 133Xe SPET and
      appropriately thresholded 3D displays efficiently localized a total of 36
      retention sites; 19 (52.7%) of these sites were not localized by CT because they
      were within the widely or homogeneously spreading non-bullous emphysematous lung
      tissues. The 3D displays enhanced the perception of anatomical configurations and
      the extent of 133Xe retention compared with multislice tomograms.
      Postoperatively, 3D fusion display visualized the details of regional changes in
      retention, and changes in the retention index on the 3D display with a
      standardized threshold correlated well with changes in 133Xe clearance time
      (T1/2) and %FEV1 (r = 0.881 and 0. 856, respectively; P<0.0001). This preliminary
      study indicates that 133Xe SPET and appropriately thresholded, topographic 3D
      displays are of potential use in selecting resection targets for LVRS, and in
      evaluating the treatment effects on regional ventilation.

PMID- 9553172
TI  - A clinical evaluation of the quantitative accuracy of simultaneous
      emission/transmission scanning in whole-body positron emission tomography.
AB  - We present a clinical evaluation of the quantitative bias which is introduced
      during simultaneous emission/transmission (SET) acquisition for the application
      of whole-body positron emission tomography (PET) with fluorine-18 2-fluoro-2
      deoxy-d-glucose. The quantitative accuracy of the SET technique was assessed by
      means of a clinical study involving 28 patients and a realistic phantom
      experiment. In the clinical study, SET overestimated the activity concentration
      in the tumours by a factor of approximately 1.10, but in the phantom study, where
      the tumours were smaller, the bias was found to increase to a value of 1.39. The
      bias in the soft tissue regions of the patient studies varied between 1.03 and
      1.36, and close agreement was observed with the corresponding phantom results.
      The extent of the bias increased as the local activity concentration decreased
      and we attribute the effect to scattered photons from the transmission source
      which are detected in the emission window during SET.

PMID- 9553173
TI  - Targeting of cholecystokinin-B/gastrin receptors in vivo: preclinical and initial
      clinical evaluation of the diagnostic and therapeutic potential of radiolabelled
      gastrin.
AB  - The outstanding sensitivity of pentagastrin in detecting the presence of primary,
      recurrent or metastatic medullary thyroid cancer (MTC) suggests widespread
      expression of the corresponding receptor type in human MTC. Indeed, recent
      autoradiographic studies have demonstrated the presence of cholecystokinin (CCK)
      B (= gastrin) receptors not only in more than 90% of MTCs but also in a high
      percentage of small cell lung cancers, stromal ovarian cancers, astrocytomas and
      several other tumour types. The aim of this study was to evaluate whether
      radiolabelled gastrin may be suitable for targeting CCK-B receptor-expressing
      tumours in vivo. For this purpose, the biodistribution of the radioiodinated
      human heptadecapeptide gastrin-I was studied in nude mice bearing subcutaneous
      xenografts of the human MTC cell line, TT. Initial therapy experiments were
      undertaken. Finally, the biodistribution of iodine-131- labelled gastrin-I was
      studied in a patient with metastatic MTC. At a peptide amount of approximately 1
      microg, maximum tumour uptake (8.9+/-2.9%ID/g) was observed in animals at 1 h
      post injection, with tumour-to-blood ratios as high as 6.3+/-1.9. Physiological
      CCK-B receptors in the stomach, gallbladder and pancreas of the mice were
      targeted as well. The major route of excretion was renal, but strong evidence for
      a biliary excretion pathway also exists. Pilot therapy studies with 131I-labelled
      gastrin showed significant anti-tumour efficacy as compared with untreated
      controls. In accordance with the preclinical data, good receptor targeting was
      observed in the tumour sites, stomach, gallbladder and pancreas of a patient with
      metastatic MTC. These data suggest that gastrin and its analogues may represent a
      useful new class of receptor binding peptides for diagnosis and therapy of a
      variety of tumour types, including MTC and small cell lung cancer. Future
      preclinical and clinical studies will address in more detail the molecular
      features that render CCK-B receptor binding agents potentially useful candidates
      for in vivo scintigraphy and radionuclide therapy.

PMID- 9553174
TI  - Value of thallium-201 scintigraphy for primary tumour detection in patients with
      malignant neck masses.
AB  - The aim of this study was to assess the contribution of thallium-201 scintigraphy
      to primary tumour detection in patients with malignant neck masses and to
      evaluate its sensitivity and specificity. A total of 30 patients with
      histopathologically proven malignant tumours were included in the study. The
      sensitivity, specificity and accuracy of 201Tl scintigraphy were found to be 54%,
      75% and 57% respectively. These results suggest that 201Tl scintigraphy has a
      limited value in the detection of the primary tumour in patients with malignant
      masses of the neck.

PMID- 9553175
TI  - Cardiac sympathetic neurotransmission scintigraphy.

PMID- 9553178
TI  - Prenatal and neonatal intussusception.
AB  - Intussusception found in the 1st month of life is rare and usually discussed as
      one entity, neonatal intussusception, but in fact, includes the intussusceptions
      occurring both prenatally and neonatally, of which the clinical presentations and
      results are different. Four full-term babies with prenatal intussusception
      presenting as intestinal atresia (IA) and three premature babies with neonatal
      intussusception mimicking necrotizing enterocolitis (NEC) are presented. Prenatal
      intussusception, as one of the causes of IA produces prominent signs of
      intestinal obstruction immediately after birth. Preoperative evaluation usually
      fails to yield a definitive diagnosis, but surgery is usually performed in time
      and is successful. In neonatal intussusception, full-term infants usually have a
      pathological lead point and the colon is almost always involved. A barium enema
      is thus useful in diagnosis. Premature babies, on the other hand, rarely have a
      colonic component, and the clinical features are insidious and similar to NEC.
      This results in diagnostic confusion that may lead to a dangerous delay in
      appropriate surgical correction. A high level of suspicion about this condition
      in cases diagnosed presumptively with NEC is important. Serial abdominal
      sonograms may be helpful in the early diagnosis of neonatal intussusception.

PMID- 9553179
TI  - Active collagen synthesis in infantile hypertrophic pyloric stenosis.
AB  - M-57 antibody, which is capable of distinguishing newly-synthesized type I
      procollagen from fully-processed, mature collagen, was used to examine the
      expression of collagen synthesis in hypertrophic pyloric muscle from patients
      with infantile hypertrophic pyloric stenosis (IHPS). Seven specimens from IHPS
      patients were removed at the time of operation; age-matched normal pyloric tissue
      of 5 post-mortem cases was obtained as controls. Immunohistochemistry was
      performed using antibody of the amino-terminal end of the procollagen type I
      propeptide (M-57). Newly-synthesized procollagen (M-57) was strongly detected in
      both the connective tissue septa between circular muscle bundles, and among the
      circular-muscle fibers in patients with IHPS. No M-57 staining was observed among
      the circular-muscle fibers in controls. Our findings show that the hypertrophic
      circular muscle in IHPS is actively synthesizing collagen, and this may be
      responsible for the characteristic "firm" nature of the pyloric tumor.

PMID- 9553180
TI  - Laparoscopic pyloromyotomy: a safer technique.
AB  - A modified technique of laparoscopic pyloromyotomy was used to treat infantile
      hypertrophic pyloric stenosis. Introducing a 5-mm periumbilical port for
      visualization, two stab wounds are made on either side laterally to directly
      insert 2.7-mm instruments for manipulation. From the left, the stomach is grasped
      - not the duodenum! From the right, an inexpensive disposable arthroscopy knife
      is used to incise the serosa and begin the myotomy, which is completed with a
      laparoscopic spreader until the muscle is separated sufficiently to relieve the
      obstruction. Twenty-nine children treated with laparoscopic pyloromyotomy were
      compared to 125 children treated with the conventional open Ramstedt
      pyloromyotomy. There were no statistically significant differences in the
      presentation or results between groups, suggesting that the laparoscopic
      technique is a safe and equal alternative.

PMID- 9553181
TI  - Pathogenesis of infantile hypertrophic pyloric stenosis: recent progress.
AB  - Although infantile hypertrophic pyloric stenosis (IHPS) is the most common
      condition requiring surgery in the first few months of life, its pathogenesis is
      not fully understood. Reviews of the recent progress in the pathogenesis of IHPS
      show: (1) there is increasing evidence to suggest that smooth-muscle cells in
      IHPS are not properly innervated; (2) because non-adrenergic, non-cholinergic
      nerves are mediators of smooth-muscle relaxation, it is likely that the absence
      of these nerves in pyloric muscle is the cause of excessively contracted
      hypertrophic circular pyloric muscle; (3) there are abnormal amounts of
      extracellular matrix proteins in hypertrophic pyloric muscle. Circular muscle
      cells in IHPS are actively synthesizing collagen, and this may be responsible for
      the characteristic "firm" nature of the pyloric tumor; and (4) the increased
      expression of insulin-like growth factor-I, transforming growth factor-beta 1,
      and platelet-derived growth factor-BB and their receptors in hypertrophic pyloric
      muscle suggests that increased local synthesis of growth factors may play an
      important role in smooth-muscle hypertrophy in IHPS.

PMID- 9553182
TI  - Increased insulin-like growth factor-I mRNA expression in pyloric muscle in
      infantile hypertrophic pyloric stenosis.
AB  - The etiology of infantile hypertrophic pyloric stenosis (IHPS) is unknown.
      Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that elicits
      various biological activities (cellular growth, replication, and differentiation)
      by binding to its receptors. IGF-I has been suggested to play an important role
      in both gastrointestinal (GI) maturation and smooth-muscle-cell (SMC)
      hypertrophy. Full-thickness muscle biopsy specimens were obtained from 8 IHPS
      patients (age range 14-64 days, mean 28.1 days) at pyloromyotomy and from 8 age
      matched controls (15-60 days, mean 33.8 days) without GI disease at autopsy. In
      situ hybridization was performed using an IGF-I-specific and digoxigenin (DIG)
      labeled oligonucleotide probe and visualized by nitroblue tetrazolium staining.
      In normal controls, IGF-I mRNA expression was absent or weak in both circular and
      longitudinal smooth-muscle layers of pyloric muscle. In contrast, the pyloric
      muscle in IHPS patients demonstrated strong IGF-I mRNA expression in the circular
      smooth-muscle layer and moderate expression in the longitudinal smooth-muscle
      layer. The increase in IGF-I mRNA in pyloric muscle in IHPS suggests that SMCs
      are actively synthesizing IGF-I, contributing to the development of pyloric
      muscle hypertrophy.

PMID- 9553183
TI  - Endoscopic treatment of recurrent tracheo-oesophageal fistulae: long-term
      results.
AB  - Recurrent tracheo-oesophageal fistula (RTOF) occurs in 5%-15% of patients
      following oesophageal atresia repair. Re-thoracotomy is technically challenging
      and associated with significant morbidity, including a re-fistulation rate of 10%
      22%. Endoscopic occlusion of the RTOF with tissue adhesives (fibrin glue,
      Histoacryl) is reported to be safe and highly effective. However, long-term
      results of such therapy are absent from the literature. A postal survey of 13
      institutions reporting the use of such treatment regimes for RTOF in the
      literature between 1974 and 1995 was performed, and data collected concerning the
      long-term outcomes of their reported patients. Eleven institutions responded to
      the request for data, providing 22 patients (age range 1 month to 12 years) for
      review. All had undergone initially successful RTOF closure by endoscopic methods
      and had been followed up for a median of 107 months (range 3-264 months). There
      was no morbidity or mortality directly related to the procedure. Overall, only
      55% of these endoscopically treated fistulas remained closed long-term. Fistula
      recurrence invariably occurred within 12 months of successful therapy (median 46
      days, range 9-335). Most patients required multiple endoscopic procedures to
      achieve successful RTOF closure (median 2.0, range 1-4 attempts), although
      significantly fewer attempts were required with fibrin glue therapy. Surgical re
      exploration remains the treatment of choice in the fit child. Endoscopic therapy
      offers a safe and elegant alternative to high-risk surgery in the sick child,
      although repeated treatments may be required for successful RTOF closure.

PMID- 9553184
TI  - Gastrointestinal tract perforation due to blunt abdominal trauma.
AB  - A retrospective clinical study was performed to evaluate the etiology, diagnosis,
      and management of gastrointestinal tract perforation (GITP) due to blunt
      abdominal trauma (BAT) in order to find a predictor to avoid delay in diagnosis.
      Thirty-five children with GITP out of 805 BAT victims (4.3%) over a 21-year
      period formed the study group. Different parameters including preoperative
      (mechanism of injury, abdominal and X- ray findings at presentation, diagnostic
      modalities), operative (type and site of GITP, intra-abdominal associated
      injuries, surgical method), and postoperative (complications, mortality) status
      were analyzed. The patients were subdivided according to their initial clinical
      presentation as group I: evidence of peritonitis (n = 19, 54%); group II:
      abdominal findings such as distension, minimal tenderness, and guarding (n = 10,
      29%); and group III: normal abdominal findings (n = 6, 26%). These groups were
      also statistically compared to each other with regard to the parameters mentioned
      above. The Mann-Whitney U, Wilcoxon rank-sum, and Kruskal-Wallis tests were used
      for statistical analysis. P < 0.05 was considered to be statistically
      significant. There were 28 boys and 7 girls; the mean age was 8.2 +/- 2.4 years.
      Mechanisms of injury were motor vehicle accidents (MVA) (60%), falls (26%), and
      bicycle accidents (BA) (14%). Group I patients presented with significantly
      higher transaminase levels and white blood cell counts than groups II and III.
      Group I patients and MVA victims were operated upon significantly earlier than
      group III patients and BA victims because of significantly earlier development of
      clinical signs of peritonitis. A significantly higher number of multiple
      perforations was encountered in Group I and MVA victims than in groups II and III
      and BA victims. The presence of multiple perforations correlated significantly
      with the earlier development of clinical signs of peritonitis. The analysis of
      site of perforation with regard to the other parameters did not differ
      significantly. Fifty-four percent (n = 19) of the patients presented with
      peritonitis; a pneumoperitoneum was detected in 46% (n = 16). Diagnosis was
      accomplished by plain radiographs, ultrasound, computed tomography, and, most
      importantly, frequent abdominal examination of the patient. The sites of
      perforation were the stomach (4), duodenum (2), jejunum (11), ileum (12), jejunum
      and ileum (3), colon (2), and ileum and colon (1). Simple closure was the most
      common surgical procedure (n = 21), followed by resection and anastomosis (n =
      12) and simple closure plus creation of a proximal ostomy (n = 2). Two deaths
      (5.7%) were directly due to head injuries. Our experience revealed that in spite
      of advanced imaging and laboratory modalities, frequent evaluation of the patient
      by an experienced surgeon is still the most important tool for early diagnosis
      and appropriate treatment. A child with BAT should be an inpatient and a high
      index of suspicion is always required, even in the presence of normal abdominal
      findings.

PMID- 9553185
TI  - Is acute appendicitis different in patients with sickle cell disease?
AB  - Nine patients with sickle cell disease (SCD) were operated upon at our hospital
      for acute appendicitis, comprising only 0.43% of the total appendicectomies
      performed at our institution. Three appendices were acutely inflamed and six
      (66.7%) were perforated. Histologic evaluation of the six perforated specimens
      revealed congestion and haemorrhage by sickled erythrocytes (RBCs) in addition to
      acute transmural inflammatory cell infiltrates. The mucosa was extensively
      ulcerated, with haemorrhage both within the lumen and in the appendiceal wall.
      The blood vessels were dilated and packed with sickled RBCs. Two of the three
      acutely inflamed appendices showed features of acute transmural appendicitis,
      with marked congestion and haemorrhage by sickled RBCs. The third did not show
      any acute inflammatory cell infiltrate, however, the mucosa was partly ulcerated
      with both mucosal and intraluminal haemorrhage. These findings suggest that acute
      appendicitis is different in patients with SCD: while it is not common, when it
      does develop it has a rapid course with a high incidence of perforation due to
      blockage of appendiceal vessels by sickled RBCs, leading to transmural necrosis.

PMID- 9553186
TI  - Timing of colonic necrosis in hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) consists of an acute onset of microangiopathic
      hemolytic anemia, thrombocytopenia, and renal dysfunction. HUS-associated colitis
      can be seen in up to 100% of patients and is usually associated with severe
      abdominal pain and distention. Colonic perforation is a complication of HUS that
      has a reported incidence of 1%-2%, and although there are several case reports in
      the literature describing perforation of the colon, it is still very difficult to
      discern the abdominal symptoms associated with HUS colitis from perforation. Four
      cases of colonic perforation are reported here from a consecutive series of 57
      patients, in which a trend in the length of time from the onset of symptoms of
      HUS to colonic perforation was determined. A review of the literature for cases
      of HUS-associated colonic perforation was also performed. The time from the onset
      of HUS symptoms to colonic perforation in our series was similar to that found in
      the literature review (11 +/- 5 vs 14 +/- 8 days). Awareness that this
      complication has a tendency to occur towards the end of the 2nd week during the
      course of HUS is essential to avoid an unnecessary and untimely surgical
      intervention.

PMID- 9553187
TI  - Fetal adrenal transplants respond to ACTH and prevent addisonian crisis in
      adrenalectomized rats.
AB  - The present study investigates whether fetal adrenal transplants into the omentum
      of adrenalectomized rats will be integrated into the recipient's endocrine system
      to provide competent adrenocortical function. The results demonstrate that fetal
      adrenals graft with a rich vascular supply, mature histologically, and produce
      increasing levels of corticosterone. When bilateral adrenalectomy is performed in
      the recipient, survival is prolonged and addisonian crisis can be prevented.
      Moreover, adrenocorticotrophic hormone levels decrease with increasing levels of
      corticosterone, indicating that the fetal grafts are integrated into the
      physiological pituitary-adrenocortical feedback system.

PMID- 9553188
TI  - Conservative management of fistula in ano in infants.
AB  - We analyzed the natural course of fistula in ano (FIA) and/or perianal abscess
      (PAA) in 97 children (male: 90, female: 7) and recommend conservative management
      in infants. Nearly one-half of these children had no recurrent episodes, and 80%
      of the infants recovered spontaneously within their 1st year of life. A radical
      operation was required in only 6 children after 2 years of age. Two-thirds of the
      children with a PAA did not develop fistula. Of the children who developed FIA,
      42% had no recurrence. Although the duration of FIA was relatively longer than
      that of PAA, 55% of the children were cured within 1 year. PAA and/or FIA in
      infants is likely to be a period-limited disorder that occurs mainly in infancy
      and spontaneously resolves within 1 year of life. Fistulotomy or fistulectomy
      should be avoided in infants.

PMID- 9553189
TI  - Endoscopic and minimal open surgical incision of ureteroceles.
AB  - Ureterocele decompression by endoscopic or open incision was the primary
      treatment in 59 children with 63 ureteroceles. Of these, 18 were intravesical and
      45 were ectopic. The endoscopic or open incision adequately decompressed all
      intravesical ureteroceles and 37 of 45 ectopic ureteroceles (82%). After
      incision, the secondary operation rate was 17% for intravesical and 62% for
      ectopic ureteroceles. In our opinion, endoscopic or open incision must be
      considered a definitive treatment in the large majority of intravesical
      ureteroceles and is also valid in ectopic ureteroceles. In these cases, the early
      decompression obtained by this approach produced significant functional recovery,
      fewer urinary tract infections, and facilitated subsequent surgery in those
      patients requiring complete surgical reconstruction.

PMID- 9553190
TI  - Management of nocturnal enuresis in children with desmopressin and bladder
      physiotherapy.
AB  - In the last 2 years, 29 children with nocturnal enuresis were treated in the
      outpatient departments of the Departments of Urology and Pediatric Surgery of the
      Aristotle University, Thessaloniki. There were 22 boys and 7 girls aged 7 to 12
      years. The clinical examination was normal in all cases. All children had
      undergone various treatments with no beneficial effect, and relapses had
      occurred. The patients were given desmopressin (DDAVP) nasal drops in combination
      with bladder physiotherapy; 77% were cured after 12 months. Physiotherapy
      improves the percentage of cures as the functional capacity of the bladder
      increases.

PMID- 9553192
TI  - Antenatal rupture of a diverticular rectal duplication with neonatal perineal
      fistulization.
AB  - A cystic pelvic malformation was found in a fetus on antenatal sonography (US) at
      26 weeks of gestational age that was no longer present 3 weeks later on control
      US. The male child presented at birth with a right-sided perineal mass that
      fistulized with meconial drainage. A radiopaque enema showed a low posterior
      rectal fistula filling a poorly delineated pouch. Surgery performed through a
      posterior sagittal approach allowed identification and closure of the fistula and
      pouch drainage. The diagnosis of a diverticular rectal duplication was
      considered, although no intestinal lining was observed macroscopically or
      histologically. The child's anorectal function was normal after a 20-month follow
      up. Labeling of the malformation and embryological hypotheses are discussed since
      the case does not fulfill all the criteria of an intestinal duplication. Surgical
      techniques are discussed, with an emphasis on the sagittal posterior approach.

PMID- 9553191
TI  - Coeliac axis thrombosis associated with the combined oral contraceptive pill: a
      rare cause of an acute abdomen.
AB  - We report a case of coeliac axis thrombosis and splenic infarction presenting in
      a girl of 14 years who had been on the oral contraceptive pill (OCP), Marvelon
      (ethinyloestradiol 30 microg plus desogestrel 150 microg, Organon, Cambridge,
      UK), for 3 weeks. She had no other risk factors for thrombo-embolism. Diagnosis
      was made with duplex Doppler ultrasound and confirmed with dynamically-enhanced
      comput-ed tomography and magnetic resonance angiography, thus avoiding the need
      for percutaneous arteriography. Though mesenteric thrombo-embolic disease is
      recognised in association with use of the combined OCP, it has not previously
      been reported to affect the coeliac axis. Paediatricians and surgeons should be
      aware of the risks to young girls on the OCP, and consider it in their
      differential diagnosis of the acute abdomen.

PMID- 9553193
TI  - Upper pole pelviureteric junction obstruction.
AB  - A case of neonatal hydronephrosis affecting the upper moiety of a duplex kidney
      is presented. In addition to the ectopic insertion of the upper-pole ureter into
      the urethra, the ureter was obstructed by the lower pole at its pelviureteric
      junction.

PMID- 9553194
TI  - Wilms' tumor presenting as Cushing's syndrome.
AB  - We report a 2-year-old boy presenting with Cushing's syndrome caused by a Wilms'
      tumor. This is the fifth such case reported in the English literature.

PMID- 9553195
TI  - Juvenile (calcifying) aponeurotic fibroma of the neck.
AB  - A case of juvenile (calcifying) aponeurotic fibroma (JAF) arising in the neck of
      a 5-year-old female is presented. The lesion was misdiagnosed as fibrous
      hamartoma of infancy (FHI) on a superficial biopsy prior to total excision of the
      mass. Only one instance of JAF of the neck has previously been reported; the
      tumor is usually located in the distal extremities and often recurs following
      excision. FHI occurs most frequently at and about the axilla and shoulder, and
      does not recur in most instances.

PMID- 9553196
TI  - The doughnut sign: an ultrasound finding in pediatric intestinal Burkitt's
      lymphoma.
AB  - This paper describes a doughnut-like ultrasound (US) finding in pediatric
      intestinal Burkitt's lymphoma. A 9-year-old boy had a fist-sized, hard, non
      movable mass in the lower abdomen. US showed a thickened, layered ring like a
      doughnut. The outer, low-level echoes seemed to be consistent with mucosa and
      muscle layers and the inner, high-level echoes seemed to be intraluminal air or
      mucus. The serum lactic dehydrogenase level was high. At surgery, a solid, hard
      tumor 15 x 10 cm in size was found in the jejunum. The intestinal wall was
      diffusely thickened with an intact mucosa. From this experience, the US doughnut
      sign may be a helpful diagnostic finding in pediatric intestinal Burkitt's
      lymphoma.

PMID- 9553197
TI  - Two children with xeroderma pigmentosum developing two different types of
      malignancies simultaneously.
AB  - Patients with xeroderma pigmentosum (XP) are highly sensitive to ultraviolet
      radiation and prone to develop multiple skin malignancies. We report two children
      under 6 years of age with XP who each developed two histologically different
      types of malignancies simultaneously. We conclude that it is of importance to be
      aware of the possibility of multiple malignancies of different types, even in
      young children.

PMID- 9553198
TI  - Papillomavirus-induced genital warts in a girl--management by surgery and
      immunomodulating therapy.
AB  - A 4-year-old girl with condylomata acuminata of the vulva and papular warts of
      the surrounding skin is presented. The lesions were removed by surgery.
      Histologic investigation showed koilocytosis of the squamous epithelium and in
      situ hybridization revealed human papilloma virus type 6 infection. There were no
      signs of sexual abuse or sexual transmission of the virus. After ablation, an
      interferon-containing ointment was applied. In order to prevent recurrence, a low
      molecular-weight immunomodulating leucocyte fraction was given for more than 1
      year, during which time no relapse was observed.

PMID- 9553199
TI  - Cutaneous angiosarcoma of the distal extremity.
AB  - A case of childhood cutaneous angiosarcoma is presented to emphasize the
      importance of accurate histological diagnosis in lymphovascular malformations
      that behave atypically and to review the natural history, aetiology, and
      differential diagnosis of this condition.

PMID- 9553200
TI  - [The heart and kidney].

PMID- 9553201
TI  - [The intestine as an immunological organ].
AB  - The intestinal mucosa is in close contact with a large number of foreign antigens
      and mitogenic substances in the gut lumen. To protect the host against invasion
      of potential pathogens or an inappropriate immune response to the enormous number
      of antigens, a highly specialized immune system in the intestinal mucosa has
      developed, the so-called gut-associated lymphoid tissue (GALT). The passage of
      viable bacteria from the gastrointestinal tract through the epithelial mucosa is
      called bacterial translocation. Bacterial translocation in critically ill
      patients may lead to a significant incidence of systemic sepsis. This has
      attracted much clinical interest, as it has been shown that disturbances of the
      GALT and malnutrition itself, impair various aspects of barrier function. Enteral
      nutrition seems to be superior to parenteral nutrition in maintaining the
      functional barrier of the gut. Defined dietary variable (fibre, glutamine)
      influence bacterial translocation. Future therapeutic strategies should therefore
      concentrate on early enteral feeding in traumatised patients to reduce the
      incidence of bacterial translocation and septic complications.

PMID- 9553202
TI  - Detection of mi transcription factor (MITF) mRNA in a case of myelodysplastic
      syndrome and bone marrow mastocytosis.
AB  - Myelodysplastic syndromes (MDS) may be accompanied by systemic mastocytosis. The
      mechanisms which play a role in the evolution of mastocytosis, however, are not
      well understood. We report on a case of refractory and anemia with ringed
      sideroblasts (RARS), and co-existing bone marrow mastocytosis. Compact mast cell
      (MC) infiltrates were detected in bone marrow sections by immunohistochemistry
      using an antibody to tryptase. In addition, the MC were found to express c-kit,
      the tyrosine kinase receptor for MGF (mast cell growth factor = stem cell factor,
      SCF). Activating point mutations in the kinase domain of c-kit (often found in
      mastocytosis) were not detectable. However, the mononuclear cells (MNC) of the
      bone marrow expressed mRNA specific for MITF, a transcription factor that
      regulates expression of c-kit and differentiation of MC. Surprisingly, the c-kit
      ligand SCF was found to augment expression of MITF mRNA in bone marrow MNC.
      Whether this augmentation represents a general response (preventing loss of
      growth factor receptor expression during cell maturation) common to all types of
      hemopoietic progenitors, or is confined to (some forms of) mastocytosis, remains
      unknown.

PMID- 9553203
TI  - Relationship between kidney function, hemodynamic variables and circulating big
      endothelin levels in patients with severe refractory heart failure.
AB  - Fluid retention is a major characteristic of symptomatic, progressive heart
      failure when a main factor implicated in the pathogenesis of renal dysfunction is
      renal hypoperfusion. This may be a consequence of forward cardiac failure,
      resulting in a low cardiac output integrating poor left ventricular function
      secondary to myocardial impairment and increased resistance in the regional renal
      vasculature secondary to locally released vasoconstrictors, e.g. endothelin. So
      far, the role of the pulmonary circulation in perpetuating renal dysfunction in
      heart failure is unclear. METHODS: We investigated the relationship of
      hemodynamic variables obtained during right heart catheterization and plasma big
      endothelin levels to renal function variables in 18 male patients aged 52 +/- 3
      years, with heart failure in the NYHA function class III-IV, based on idiopathic
      causes in 8 and ischemic causes in 10 patients. Renal plasma flow (RPF) was
      established by paraaminohippurate (PAH) clearance and the glomerular filtration
      rate (GFR) was measured by iothalamate clearance. RESULTS: Plasma big endothelin
      (ET) levels were increased above the upper normal range (1.8 fmol/ml) in 16 out
      of 18 patients, averaging 5.0 +/- 0.8 fmol/ml (1.7-11.9 fmol/ml). Positive
      correlations to big ET plasma levels were detected with mean pulmonary pressure
      (r = 0.73, p < 0.001) pulmonary capillary wedge pressure (r = 0.56, p < 0.05) and
      pulmonary vascular resistance index (r = 0.69, p < 0.01). Glomerular filtration
      rate (70 +/- 7 ml/min) and renal plasma flow (358 +/- 36 ml/min) were
      considerably reduced and exhibited a tendency to correlate inversely with big ET
      levels (r = -0.46, p = 0.056 and r = -0.44, p = 0.069, respectively). Contrary to
      expectations, RPF did not correlate significantly with cardiac index, systemic
      vascular resistance index or arterial blood pressure. In contrast, significant
      correlations were detected of RPF with pulmonary capillary wedge pressure (r = 
      0.69, p < 0.01), mean pulmonary artery pressure (r = -0.65, p < 0.01), right
      atrial pressure (r = -0.47, p < 0.05) and right ventricular ejection fraction (r
      = 0.49, p < 0.05). CONCLUSION: The findings suggest a role for endothelin in
      renal vasoconstriction and accord well with the concept that in severe heart
      failure renal hypoperfusion--by volume retention--as well as increased endothelin
      synthesis--by pulmonary vasoconstriction--play a part in the increased pulmonary
      filling pressures.

PMID- 9553204
TI  - Protective effects of sucralfate and omeprazole on gastric mucosal damage induced
      by ethanol in rats.
AB  - Studies on the protective effect of omeprazole, a proton-pump inhibitor, against
      damage to the rat gastric mucosa induced by strong irritants, are few and
      contradictory. We have investigated the protective effects of omeprazole and
      sucralfate against gastric mucosal damage induced by ethanol in rats. The study
      was performed on 4 groups of 10 rats each. Group A received omeprazole 7
      mg/kg/day intraperitoneally (i.p.) for 7 days. Group B received an equivalent
      volume of 0.9% sodium chloride i.p. for 7 days, while no drugs were given to
      groups C and D. After 1 week, following 24 hours of fasting, group A received
      omeprazole 7 mg/kg, group B received an equivalent volume of 0.9% sodium chloride
      group C received omeprazole 7 mg/kg i.p. and group D received sucralfate, 100
      mg/kg intragastrically (i.g.). 4 hours after groups A, B and C received the last
      medication and 30 minutes after group D received sucralfate, ethanol 95% was
      given i.g. All rats were sacrificed 1 hour after ethanol application and their
      stomachs were removed for macroscopic and microscopic examination. It was found
      that sucralfate was effective in preventing gastric lesions induced by ethanol.
      There was a significant difference between the sucralfate group and the other
      group (p < 0.001). Omeprazole was ineffective in preventing gastric lesions,
      either given as a single dose or after administration for 7 days. Our results
      indicate that sucralfate has a protective effect on gastric lesions induced by
      ethanol and omeprazole applied i.p. has no protective effect.

PMID- 9553206
TI  - [Pain therapy only for specialists or general responsibility?].

PMID- 9553205
TI  - [Gastrointestinal hemorrhage after operation for dissecting aneurysm of the
      thoracic aorta].
AB  - We present the case of a 45-year-old man who underwent surgical repair of a
      dissecting aneurysm of the descending thoracic aorta. 25 days postoperatively,
      the patient unexpectedly developed hematemesis and hypovolemic shock. Emergency
      gastroscopy was performed and a suspected aortoesophageal fistula was diagnosed.
      Unfortunately, the patient died prior to emergency surgery. Aneurysms of the
      aorta or of aortic grafts occasionally lead to the development of fistulae to the
      upper gastrointestinal tract. Once this rare, but life-threatening complication
      is suspected, endoscopy must be performed immediately. Emergency surgery is
      associated with a high risk, but represents the only possibly chance of survival
      for the patient.

PMID- 9553207
TI  - [Headache--differential diagnosis and therapy].
AB  - Only few guidelines exist for the therapy of chronic pain syndromes but are
      available for headache. It is important to know the therapeutic principles and
      apply them to the patients. The education of a patient suffering from headache is
      a main factor for a successful therapy. Physician and psychologist together in
      cooperation with the patient can achieve a better quality of life for the
      patient. New developments of the medication used for the therapy of chronic
      headache will result in a better symptom control in the next years.

PMID- 9553208
TI  - [Backache--diagnosis, therapy and prognosis].
AB  - Back pain is a common disease causing tremendous costs for treatment,
      rehabilitation, pension payments and work-loss. The reasons of back pain vary
      considerably and often remain doubtful. The effectiveness of current treatment
      concepts has not yet been proven significantly. In accordance with the
      literature, in chronic pain only multimodal concepts of treatment seem to be
      successful as far as they take care about somatic, psycho-social, and sport
      physiological aspects.

PMID- 9553209
TI  - [Therapy of tumor pain].
AB  - The incidence of cancer pain is about 90%. The first step in the treatment
      strategy is a causal therapy, including tumor mass reduction. An adequate pain
      management should start sometimes before the onset of a causal treatment. A good
      pain relief in cancer patients is mostly possible by the consequent application
      of the World Health Organisation 3 step analgesic ladder for the treatment of
      cancer. Pain management has become more comfortable since the development of new
      ways of applications e.g. transdermal fentanyl, water soluble morphine granulate
      and retarded drugs. With those new preparations, we got new possibilities and a
      bigger variety in the practical use of the WHO analgesic ladder. Basics for a
      good social integration of the patient are treatment of side effects, periodic
      consultations and a professional psychological support.

PMID- 9553210
TI  - [Indications and limits of nerve block techniques].
AB  - Repetitive nerve blocks as a monotherapeutic treatment are loosing importance in
      the therapy of chronic pain. Such invasive methods for pain reduction are just
      one strategy in the interdisciplinary and multimodal planning of pain therapy.
      They are mostly used in special indications, e.g. reflex sympathetic dystrophy
      neurolysis in S3-S5 localized cancer pain. Premises for an invasive pain therapy
      are the patient's knowledge and agreement concerning this method. Furthermore, it
      is necessary for the physician to know the typical complications of the invasive
      treatment and to be able to manage them. It is recommended to document the pain
      course.

PMID- 9553211
TI  - [Sympathetic reflex dystrophy and phantom pain. Diagnosis, therapy and
      prognosis].
AB  - The incidence of phantom limb pain has been significantly underestimated for many
      years. However, studies published during the recent decade indicate that the real
      incidence of phantom limb pain may be between 60% and 90%. Reflex sympathetic
      dystrophy (RSD) occurs with an incidence of about 15.000 new cases every year in
      Germany. Both diseases show early centralisation and chronification. Hence, only
      early diagnosis and onset of correct therapy in time provide significant pain
      reduction. When therapy is started too late, prognosis in regard to sufficient
      pain reduction is poor. Phantom limb pain can be prevented by proper anaesthesia.
      Several studies could show the benefit of perioperative continuous regional
      anaesthesia . None of the patients treated with a combination of local
      anaesthetics and low dose morphine developed phantom limb pain. Therapy of choice
      for RSD is the sympathetic blockade. The most suitable method is intravenous
      regional sympathetic blockade (IVRSB) with guanethidine (2).

PMID- 9553212
TI  - [Non-opioid analgesics and co-analgesics in therapy of chronic pain].
AB  - Efficacy and side effects of non-opioid-analgesics were analysed in a
      standardized review of placebo-controlled or double-blind studies. In rheumatoid
      arthritis, ibuprofen showed the best ratio of effectiveness and side-effects.
      Naproxen, diclofenac and meloxicam may serve as alternatives. In osteoarthritis,
      naproxen seems to be superior to diflunisal, meloxicam and diclofenac. In cancer
      pain, ibuprofen is the treatment of the first choice followed by naproxen and
      diclofenac. No sufficient data on non-opioids in neuropathic pain were available.
      The dose administered in the management of chronic pain should be low in order to
      reduce the incidence of side-effects. The frequency of side-effect-related
      discontinuation of chronic pain medication was calculated as follows: ibuprofen
      3.8%, aspirin 4.7%, piroxicam 4.8%, naproxen 7.4%, meloxicam 13.0% and diclofenac
      17.8%. Since differences in efficacy were not clinically relevant, the indication
      for a special non-opioid-analgesic medication should focus on the prevention of
      side-effects.

PMID- 9553214
TI  - [Palliative medicine].
AB  - Palliative medicine is the care and the study of that care for patients, with an
      active, progressive, and advanced disease, where life expectancy is relatively
      short. The goal is achievement of the best possible quality of life for patients
      and their families. Pain therapy, control of other physical symptoms and of
      psychological, social and spiritual problems are cornerstones of palliative
      medicine. Skilled empathetic communication and ethical issues are essential to
      many of the aspects of palliative care. Education and training of professional
      health workers involved in the care of dying patients is important.

PMID- 9553213
TI  - [Paraspinal opioids and pump systems].
AB  - The regional application of opioids close to the spinal cord by using pumps
      induces a pain reduction comparable to the systemic medication of the WHO
      analgesic ladder. However, this method does not reduce the side effects of these
      drugs, e.g. nausea, vomiting, dysfunctional bladder emptying, and obstipation.
      Problems and complications leading to revision surgery and system explantation,
      respectively, are of more severe importance. Pump explantation occurs in a
      frequency of 7.3% and revision surgery in a frequency of 6.2%. Catheters and port
      systems have to be revised in 15% of all cases. Therefore, the indication for
      this method has to be considered carefully and includes the following criteria:
      pain of somatic origin, exclusion of mental diseases and psychogenic causes of
      pain, causal therapy is exhausted, insufficient effects of peripheral analgesics
      and co-analgesics, oral or transdermal opioids are insufficient despite dosages
      resulting in side-effects, pain is sensible to opioids, regional application of
      opioids has been tested effective before implantation.

PMID- 9553215
TI  - [Psychological pain therapy].
AB  - Psychologic strategies for the treatment of chronic pain are an important
      component of the necessary multidimensional treatment for patients in chronic
      pain. These techniques including relaxation training, biofeedback, hypnosis and
      cognitive-behavioral therapy have demonstrated efficacy. The impact of these
      techniques is on the sensory aspect of pain and the psychologic distress and on
      the maladaptive coping mechanism people develop in response to pain. In Germany
      there are still several impediments for the consequent application of psychologic
      strategies for patients with chronic pain. These impediments and possible
      solutions are discussed.

PMID- 9553216
TI  - [Economic aspects of pain therapy].
AB  - Chronic pain has an economic impact for the society and the patients suffering
      from chronic pain. The indirect costs of chronic pain (loss of productivity,
      social security payments) are higher than the direct costs (prevention, diagnosis
      and therapy). The indirect costs in the family are often underestimated. It is
      proven that in-patient and out-patient treatment in multidisciplinary pain
      centers are effective. In-patient treatment is more expensive. Multidisciplinary
      pain programmes increase the return-to-work-rate significantly. Further
      investigations are requested to uncover costs and outcome of different pain
      treatment methods.

PMID- 9553217
TI  - [Suicide in the elderly: collapse of value orientation?].
AB  - Suicide of the aged has often been understood as a careful deliberation of the
      quintessence of life. Nevertheless, it displays the breakdown or the entire lack
      of value orientation. Some gerontologists have come to terms with the fact that
      the ideal of value-free living results in the suicidality of the aged. Suicide
      seems to be a probable solution of their problems. But values regulate the social
      existence of humans. Accordingly, this paper considers suicide of the aged to be
      a result of this disorientation. Thus, it demands first of all that a rich set of
      values has to be developed, and secondly, that adequate resources of values have
      to be proposed. This can be achieved by four steps: 1) distance from the critical
      situation, 2) combination of interaction and mutual appreciation, 3) analyzing
      the reduced set of values, and 4) opening new priorities and preferences.

PMID- 9553218
TI  - [Stages in coping after stroke].
AB  - People who suffer a stroke most often experience a major crisis in their lives.
      This leads to psychological problems which are likely to influence the patient's
      life satisfaction, long-term rehabilitation outcome, and quality of life as much
      as the physical consequences caused by the stroke, The patient's ability to
      accept the new reality created by a disability as a part of their future life is
      therefore essential. This necessitates an individual coping strategy in the
      center of which is a mourning process, which unfolds in the same way as other
      experiences of vital threat, e.g. confrontation with one's own dying. Different
      stages of mourning that can also be found in stroke patients are nonacceptance of
      the facts, erupting emotions, parting with the former and finding of a new self
      as well as new perspectives for one's future. Whether a coping process is
      successful does not depend on the type of the defense mechanisms or stages, but
      essentially on their persistence. It is the task of the therapeutical team to
      support this process by applying a basic therapeutic behavior, stage-consistent
      interventions and a positive feedback. A failed process of coping may be one of
      the causes of the high prevalence of psychological disorders like depression and
      anxiety disorders in patients having suffered a stroke.

PMID- 9553219
TI  - [Clostridium difficile toxin-associated diarrhea in geriatrics].
AB  - In the course of 1 year, Clostridium difficile-associated diarrhea, which may
      lead to pseudomembranous colitis and therefore may be very harmful in frail
      elderly people, was diagnosed in six patients of a geriatric clinic. The disease
      is associated with antibiotic therapy, due to an overgrowth of the intestinal
      flora with Clostridium difficile. Symptoms varied from a state of asymptomatic
      carriage or benign diarrhea to acute stages of the disease with severe diarrhea,
      abdominal pain, fever and acute phase response. Diagnosis of Clostridium
      difficile associated diarrhea was established when, in addition to typical
      clinical symptoms, a toxin-positive stool specimen was found. Oral vancomycin was
      effective in all cases, leading to a stop in the diarrhea and an amelioration of
      systemic inflammatory parameters. According to recent results, in order to
      prevent the induction of vancomycin-resistance and in view of higher treatment
      costs, metronidazole is considered as the drug of choice in mildly and moderately
      ill patients.

PMID- 9553220
TI  - [Gerontologic studies in South Africa--a report].
AB  - The paper reviews the present state of gerontological research in South Africa
      and provides examples of relevant studies. So far, most of the research has
      focused on socioeconomic conditions, e.g, financial status, living arrangements,
      and intergeneration family relations. During recent years another topic has
      gained prominence, e.g., the subjective well-being of the elderly. Another aspect
      of research in this area is its inter- and multidisciplinary nature and its
      concern with practical relevance. Terms often used in new research on aging are
      "empowerment of the elderly" and "self-care strategies". In this context, the
      elderly are beginning to be considered as significant brokers in development
      planning. In the last part of the paper, the trend to qualitative methods is
      discussed.

PMID- 9553221
TI  - [How does subjective well-being of elderly patients during inpatient geriatric
      rehabilitation change?].
AB  - During rehabilitation of patients suffering from a recent hip fracture, we
      evaluated the development of several aspects of their subjective well-being (n =
      87, age: 70 to 94)). In most cases, a deterioration of subjective well-being due
      to the consequences of the hip fracture could be prevented; the well-being
      improved in most cases. When discharged, the subjective well-being of our
      patients was comparable to the well-being of similar-aged people living at home.

PMID- 9553223
TI  - [Management of treatment omission. Ethical problems in terminal care].
AB  - Causes and courses of the diseases are subjected to a change of an increasing
      life expectancy on the one hand and technically highly developed medicine on the
      other hand. Since a growing number of elderly people is denying intensive medical
      interventions which serve the purpose of keeping them alive despite severe
      diseases, the problem of euthanasia imposes direct questions. A central role is
      played by the active-passive difference and its moralistic legitimacy. The
      difficulties of this difference are discussed below on the applicable level of
      ethical discussions. At the same time, knowledge of the danger is being made
      aware that in a maximal therapeutical orientated medical care system the desire
      for euthanasia may become identical with the reverse side of this care system.

PMID- 9553222
TI  - [Vascular dementia--a concise concept?].
AB  - Although cerebrovascular disease are the most common causes of dementia after
      Alzheimer's disease, vascular dementia (VD) has remained so far an ill-defined
      term. The main problems in the definition of VD arise from finding criteria for
      both terms "vascular" and "dementia". The detailed criteria for the diagnosis of
      VD proposed by several groups or institutions (ADDTC, DSM-IV, ICD-10, NINDS
      ARIEN) are critically reviewed. The diagnostic value of some clinical findings,
      especially the very frequent white matter luciencies in CT (leuko-araiosis), are
      discussed. The available studies suggest a differentiation of VD into some
      subtypes (listed according to the frequency): subcortical VD, VD with acute
      onset, multi-infarct-dementia, mixed types, and specific forms. Nevertheless,
      these subtypes give only little information about the etiology of the underlying
      vascular process and, therefore, no clear indication for specific therapeutic
      strategies.

PMID- 9553224
TI  - [Home care of demented and non-demented patients. I: Utilization of professional
      home care services].
AB  - 1911 informal caregivers from the Federal Republic of Germany who care for
      someone with a chronic, non-congenital condition rendering them in need of
      physical "hands-on" nursing completed a standardized questionnaire on their
      situation as caregivers. The informants were found through magazine
      advertisements as well as through dissemination of the questionnaires via contact
      persons in the social services. Predictors of whether use is made of professional
      help or not (in-home respite and/or day-care and/or temporary institutional
      respite) are--independent of the reasons why help is necessary--the extent of the
      help that is needed and the absence of support with the family. Sociodemographic
      variables, that are age, sex, income, and education have no influence.

PMID- 9553225
TI  - [Home care of demented and non-demented patients. II: Health and burden of
      caregivers].
AB  - 1911 informal caregivers from the Federal Republic of Germany who care for
      someone with a chronic, non-congenital condition rendering them in need of
      physical "hands-on" nursing completed a standardized questionnaire on their
      situation as caregivers. The questionnaire was pertinent in particular to their
      own somatic symptoms (Giessen Symptom List, GSL) as well as their subjective
      burden (Burden Scale for Family Caregivers, BSFC). Eight out of ten caregivers in
      Germany are women. The home care of a dementia patient or of a distant or non
      related person is taken on significantly more frequently by female caregivers.
      Somatic symptoms covering the spectrum of exhaustion, aching limbs, and heart and
      stomach complaints are in greater evidence amongst caregivers of dementia
      patients than amongst those caring for elderly people with relatively unimpaired
      cognitive performance. In all, the average extent of the somatic symptoms lies
      significantly above the age and gender specific value for the general population.
      The increased subjective burden of caregivers caring for a dementia patient
      expresses itself particularly in more interpersonal conflicts and clashes of
      interest between the care given and other areas of activity.

PMID- 9553226
TI  - [Dissertation criteria].

PMID- 9553227
TI  - [Risks and protective factors in early childhood development: empirical
      findings].
AB  - A common result of many studies of children at risk for developmental disorder is
      the heterogeneity of individual reactions to adversity. One attempt to explain
      the differential outcome of children at risk lies in the assumption of protective
      factors. In a prospective study of 362 infants the significance of pre- and
      perinatal complications (early biological risks) and of adverse family living
      circumstances (early psychosocial risks) on child development at 4 1/2 years was
      examined. Additionally, to study the interplay between risk and protective
      factors a number of mother-child and family characteristics potentially
      favourable to early development were assessed. Results indicated that early risk
      factors made a significant contribution to child development at preschool age.
      Using multiple risk indices, between 10 and 20% of the variance of the
      developmental outcome at 4 1/2 years was explained. Significant predictors of
      later developmental disorders were neonatal seizures and very low birth weight
      among the biological risks and low educational level of the parents, early
      parenthood and unwanted pregnancy among the psychosocial risks. The contribution
      of early protective factors to developmental outcome, however, was only limited.
      The high overlap with risk factors, the low specific predictive power and the
      lack of a moderator effect question the theoretical usefulness of a global
      concept of protective factors. However, when interactions between specific risk
      and protective factors were studied, there was evidence of a buffer effect of a
      successful early mother child interaction.

PMID- 9553228
TI  - [Eating before of an unselected student population of the 7th to 10th grade in a
      Berlin school].
AB  - In 1990 a study of 32 girls and 44 boys in Grades 7 to 10 in a former "East
      Berlin" school in the borough of Prenzlauer Berg was carried out in continuation
      of an "East-West Berlin Study on Eating Disorders in Adolescents" which we had
      initiated in the mid-eighties. The Eating Attitudes Test (EAT), Eating Disorder
      Inventory (EDI), State of Comfort Scale (SCS) were used in a one-step study
      design together with complementary clinical and sociodemographic data, including
      body weight, height and BMI. On the whole, all students were well aware of their
      own body measurements and had definite ideas about their ideal body weight. Boys
      were less sure about their real weight, while girls showed some insecurity in
      defining their ideal weight. Regardless of weight parameters, girls were more
      strongly preoccupied with issues specific to eating disorders, such as
      dissatisfaction with their own body, the quest for a slim figure and diet. They
      were more severely affected by perceptions of insufficiency. 44% of all girls and
      4% of the boys said they had problems with their body weight. These students'
      intensive preoccupation with issues specific to eating disorders was dependent on
      their actual body weight. They exhibited more clearly pronounced psychological
      characteristics of eating disorders. Eating-related and psychological
      characteristics of eating disorders were significantly more pronounced in girls
      with irregular menstruation. The correlation between irregular menstruation and
      individually perceived weight problems was significant. These results are
      discussed in greater detail with due consideration of the need for understanding
      the specific dynamics of eating attitudes in the general population.

PMID- 9553229
TI  - [Tradition and development in child and adolescent psychiatry].

PMID- 9553231
TI  - [Dyssocial behavior and aggression: knowledge, management and knowledge gaps].

PMID- 9553230
TI  - [Biological correlates of aggressive behavior].

PMID- 9553233
TI  - Is the perception of laparoscopic technique for minor surgery such that of
      cholecystectomy right?

PMID- 9553232
TI  - [Outcome of adolescent treatment measures in dyssocial disorders].

PMID- 9553235
TI  - Patient barriers to cancer pain management: from the viewpoint of the cancer
      patients receiving analgesics in a teaching hospital of Taiwan.
AB  - BACKGROUND: The purpose of this study was to investigate the barriers to
      receiving analgesics for cancer pain in Taiwanese patients. METHODS: The sample
      consisted of 128 hospitalized patients. All of the subjects were receiving
      analgesics. Three questionnaires entitled "Barriers Questionnaire-Taiwan Form
      (BQT)", "Brief Pain Inventory Short Form", and "Pain Management Index (PMI)" were
      used in this study. Data were analyzed using Student's t-test and Pearson
      correlation. RESULTS: The results showed that most of BQT subscales including
      disease progression, time interval, tolerance, injection, addiction, fatalism and
      side effects were approaching toward the moderate or high end of the scale. 42.1%
      (n = 54) of the patients had negative PMI scores indicating that they were using
      less than adequate analgesics for pain. There was a significant difference
      between those who had adequate medication and those who did not, in terms of
      disease progression score and the total BQT score. CONCLUSIONS: Overall the
      result revealed that pain management in these cancer patients was inadequate.
      Misconceptions on the part of patients still exist. Educational intervention
      could be an effective means for overcoming such barriers in Taiwanese patients
      who received analgesics for cancer pain.

PMID- 9553234
TI  - The analgesic effect of PCA buprenorphine in Taiwan's gynecologic patients.
AB  - BACKGROUND: The aim of this study was to evaluate the analgesic effect of PCA
      buprenorphine (intravenous) on postoperative pain in gynecologic patients of
      Taiwan and the potency ratio of buprenorphine versus morphine, a commonly used
      potent analgesic. METHODS: Fifty women undergoing abdominal total hysterectomy
      under spinal anesthesia were enrolled into the investigation. Patients were
      randomly divided into 2 groups (n = 25 each). Group 1 received intravenous
      buprenorphine using PCA device for the management of postoperative pain, whereas
      Group 2 received PCA morphine for the same purpose. During the first 48 hours
      postoperatively, we collected the following data: demand and delivery of
      analgesics, pain scores, vital signs, nausea, vomiting and pruritus. RESULTS:
      Despite different treatments, we found that pain scores on day 1 and day 2
      postoperatively were low and were not significantly different between groups.
      Also, times of demand for delivery of PCA medication were not significantly
      different between groups. The cumulative consumption of buprenorphine and
      morphine within 48 h were 1.5 +/- 0.6 mg and 36 +/- 7 mg, respectively. The
      potency ratio between buprenorphine and morphine was 24:1. Both treatments showed
      only minor side effects. CONCLUSIONS: We found that PCA buprenorphine
      (intravenous) could be effective in the treatment of postoperative pain in the
      gynecologic patients in Taiwan and the potency ratio of buprenorphine versus
      morphine appeared to be 24:1.

PMID- 9553236
TI  - The efficacy of intrathecal coadministration of morphine and bupivacaine for
      labor analgesia.
AB  - BACKGROUND: Intrathecal (i.t.) opioids can provide labor analgesia, but the onset
      of pain relief is slow. Bupivacaine has the beneficial property of less motor
      blockade than other local anesthetics. This study retrospectively examined the
      efficacy of concomitant use of i.t. morphine and bupivacaine for labor pain
      relief. METHODS: Fifty five nulliparas who requested analgesia in the active
      phase (IA group) prior to a cervical dilation 3.9 +/- 0.6 cm and received i.t.
      morphine 0.5 mg and 0.1% bupivacaine 2.5 mg served as the treatment group, and 88
      similar nulliparas who did not request and receive analgesia served as the
      control group. RESULTS: The mean onset time of analgesia was 2.6 +/- 0.5 min, the
      duration was 4-12 h and 93% of parturients did not request additional analgesia
      after a single injection of i.t. morphine and bupivacaine. The active phase of
      the first and second stages of labor in the treatment group were significantly
      longer [318 +/- 214 min vs. 176 +/- 120 min; 74 +/- 29 min vs. 37 +/- 26 min].
      Frequency of instrument-assisted vaginal delivery was higher compared with the
      control group (30.9% vs. 14.1%). However, there were no significant differences
      in the rate of cesarean section and the Apgar scores of newborns at 1 min and 5
      min between the treatment and control group. The major side effects of the
      treatment group included pruritus (48%), nausea (40%), vomiting (37%), somnolence
      (27%), shivering (27%), urinary retention (21%), hypotension (15%), and
      bradycardia (13%). Most of the side effects were mild and could be alleviated by
      naloxone. Neither post-spinal headache nor respiratory depression was noted.
      CONCLUSIONS: Our results showed that a single injection of i.t. morphine and
      bupivacaine provided rapid onset and effective analgesia with manageable side
      effects and without major complications. Thus, i.t. morphine and bupivacaine
      provides an alternative to epidural analgesia for most women in labor.

PMID- 9553237
TI  - Comparison of intravenous retention of fentanyl and lidocaine on local analgesia
      in propofol injection pain.
AB  - BACKGROUND: With a tourniquet on arm for arresting venous blood flow, we
      evaluated the efficacy of intravenous (i.v.) retention of fentanyl and lidocaine
      in reducing the pain on i.v. propofol injection during general anesthesia.
      METHODS: One hundred and twelve patients were studied. Following a venous
      occlusion by a tourniquet inflated to 70 mmHg, patients in Group A (n = 38)
      received normal saline (NS) 3 ml, while those in Group B (n = 37) and in Group C
      (n = 37) respectively received fentanyl 150 micrograms or 3 ml and 2% lidocaine 3
      ml (60 mg). The venous retention of drug was maintained for 1 min, followed
      immediately by tourniquet release and propofol 100 mg i.v. injection over 20 s.
      RESULTS: Both fentanyl and lidocaine treatments (Groups B and C) were
      significantly better than placebo (Group A) in reducing pain on propofol
      injection (p < 0.005). Lidocaine 60 mg was more effective than fentanyl 150
      micrograms in reduction of pain associated with i.v. propofol (p < 0.001).
      Injection of fentanyl itself caused pain in 28% of patients as compared to 2% in
      the lidocaine group. Mild local skin erythema was noted in 14% of patients with
      fentanyl venous retention versus 0% of patients with lidocaine venous retention.
      CONCLUSIONS: Intravenous retention of fentanyl 150 micrograms, although less
      effective than that of lidocaine (p < 0.001), showed local analgesic effect in
      reducing the pain on propofol injection. The hypothetic mechanisms of action were
      speculated.

PMID- 9553238
TI  - Thromboelastographic study of thrombosis in the implantable central venous access
      device.
AB  - BACKGROUND: In the present study thromboelastography (TEG) was to study whether
      or not hypercoagulopathy might contribute to the thrombosis of implantable
      central venous access device (Port-A-Cath, Pharmacia) in cancer patients.
      METHODS: All 76 oncological patients who were enrolled in this study had their R
      time, alpha angle and MA value measured before Port-A-Cath implantation, of whom
      11 patients received re-implantation because of thrombotic device. We compared
      the measurements of these 11 patients (thrombotic group) with that of 65 patients
      (control group) who received Port-A-Cath implantation for the first time.
      According to TEG values the hemostatic status in these patients was classified as
      hypercoagulable, normal or hypocoagulable for comparison. All patients in the
      control group were followed up for 3 months for occurrence of thrombosis.
      RESULTS: It was found that no patient in the thrombotic group was associated with
      hypercoagulopathy. Five patients (7.5%) in the control group was found in
      hypercoagulable status at the time of catheter insertion but none of them
      developed clinical thrombosis during three months of observation. There was no
      significant difference between the two groups for R time, alpha angle but a
      higher MA value was found in the control group (p < 0.05). Furthermore, the
      hypercoagulability (7.5% for the control vs. none for the thrombotic group),
      hypocoagulability (1.5% vs. 9.1%) and normocoagulability (91.0% vs. 90.9%) were
      not statistically different between the two groups (Fisher exact test, P =
      0.229). CONCLUSIONS: We conclude that hypercoagulopathy in cancer patients has
      little, if any, contribution in thrombosis of the implantable central venous
      access device.

PMID- 9553239
TI  - Low-flow anesthesia in adult orthotopic liver transplantation: a preliminary
      clinical experience.
AB  - BACKGROUND: Anesthesia in orthotopic liver transplantation (OLT) may carry with
      complex hemodynamic, body temperature, and metabolic alterations. Although OLT
      cases increased in recent years in Taiwan, experiences remained limited. Notable
      advantage of low flow anesthesia may include reduced consumption of anesthetic
      gases and vapors, reduced environmental pollution and cost-saving. This study
      investigated patient profiles and the feasibility of low-flow rebreathing
      technique for adult orthotopic liver transplantation. METHODS: Since June 1996,
      there were six OLT patients who received low flow anesthesia with isoflurane. All
      patients received hepatic veno-venal anastmosis (so-called piggy back procedure).
      Two patients were excluded from this study because of different surgical
      procedure (total occlusion of inferior vena cava and inferior vena cava veno
      venal anastmosis). During maintenance of anesthesia, isoflurane was carried by a
      mixture of oxygen and air at a total fresh gas flow of 0.6 L/min. Alongside with
      the standard anesthesia machine and physiologic monitors, a newly designed Swan
      Ganz catheter was introduced to measure and record cardiac output, systemic
      vascular resistance, pulmonary artery pressure, central venous pressure, and core
      temperature in a real-time manner. Blood samples were collected at 6
      predetermined time-points in each patient for analysis of arterial blood gases,
      electrolytes, lactate and glucose concentrations. RESULTS: The anesthetic time
      was 916 +/- 26 min (900 to 930 min). All patients regained their consciousness
      within 30 min after completion of surgery. The hemodynamics were relatively
      stable except after reperfusion of the liver. There was a significant decrease in
      mean arterial blood pressure, which occurred with accompaniment of a reduction of
      systemic vascular resistance and increased cardiac output. Arterial blood gas,
      electrolyte, and glucose were, however, maintained within acceptable limits.
      Blood lactate was progressively increased and reached its peak after reperfusion
      of the liver until the end of surgery. The core temperature was well maintained
      above 34 degrees C. No patient developed hypoxia or hypercapnia. CONCLUSIONS: Low
      flow rebreathing anesthetic technique maintained acceptable patient profiles and
      good body temperature preservation in orthotopic liver transplantation. These
      characteristics make it a promising method in maintenance of anesthesia for OLT.

PMID- 9553240
TI  - Induction of tolerance to intrathecal butorphanol in rats.
AB  - BACKGROUND: Butorphanol, an opioid agonist/antagonist, has been administered
      spinally and epidurally in humans for moderate to severe pain. However, unlike
      intrathecal (i.t.) morphine, virtually no information is available regarding
      butorphanol's ability to induce analgesic tolerance at the spinal cord level upon
      chronic i.t. administration. METHODS: Continuous infusion of i.t. butorphanol was
      given via an osmotic minipump. Rats were randomly assigned to four groups (n = 7
      each) to receive i.t. infusion (1 microliter/h) consisting of saline, or
      butorphanol (13, 26, or 52 nmol/h) for 96 h. Tail-flick (TF) latencies were
      measured during the period of i.t. infusion. RESULTS: A dose-dependent
      antinociceptive effect, as measured by TF latency, was demonstrated in the groups
      receiving i.t. butorphanol as compared to the saline group. The overall
      antinociceptive effects calculated from the areas under the curve (AUC's) were
      372 +/- 3.0, 394 +/- 7.5, and 433 +/- 20 for the 13, 26, and 52 nmol/h
      butorphanol-infused groups, respectively; the AUC's of the 26 and 52 nmol/h
      groups were significantly different from the AUC of 356 +/- 3.4 for the saline
      infused group (p < 0.01, one way ANOVA; p < 0.05, post hoc Dunnett's test). The
      TF latencies of the 26 and 52 nmol/h groups were 3.77 +/- 0.05 and 3.73 +/- 0.03
      s at the baseline (before the i.t. infusion), respectively; and gradually
      increased significantly (p < 0.01, two way repeated measure ANOVA; p < 0.05, post
      hoc Student-Newman-Keuls or SNK test) to the peak values of 4.31 +/- 0.14 and
      4.90 +/- 0.28 s, respectively; then decreased significantly from the peaks (p <
      0.05, post hoc SNK test) to the final values of 3.87 +/- 0.06 and 4.10 +/- 0.13 s
      at the end of the 96-h infusion, respectively. The TF values of the saline and
      the 13 nmol/h groups did not show statistically significant differences
      throughout the 96-h infusion period. CONCLUSIONS: Therefore, continuous infusion
      of i.t. butorphanol at the rate of 26 and 52 nmol/h induced tolerance to tail
      flick analgesia within 96 h.

PMID- 9553241
TI  - Propofol anesthesia in a patient with Isaacs syndrome--report of a case and
      literature review.
AB  - Isaacs syndrome is an unusual lower motor neuron disease characterized by
      myokymia (muscle twitching), muscular stiffness, and decreased tendon reflexes.
      We reported a patient who was affected with this rare disease, with manifestation
      of involuntary muscular contractions and required general anesthesia for
      bilateral tonsillectomies. Understanding the presentation and characterization of
      this unusual disease may be helpful in making choice of anesthetics or anesthetic
      techniques. Its possible mechanisms of action and its specific considerations in
      anesthesia in the literature are reviewed and discussed.

PMID- 9553242
TI  - Hypovolemic shock induced by laparoscopic cholecystectomy--a case report.
AB  - Since its introduction and development in the 1960s, laparoscopic cholecystectomy
      has become widely accepted by the medical community and the public as the
      treatment of choice for various gallbladder disorders. We present a 46-year-old
      male who underwent laparoscopic cholecystectomy, during which inadvertent
      penetration of the first trocar resulted in injury of the abdominal aorta and
      then hypovolemic shock ensured. The time from notification of shock by the
      anesthesiologist to switch of procedure to exploratory laparotomy for stanching
      hemorrhage was twenty minutes. During the intervention, blood loss was over 3,000
      ml and despite rapid infusion of plasma expander, blood pressure could only be
      maintained between 40/18 to 60/20 mmHg. After the patient became stabilized and
      blood pressure was elevated to acceptable levels, conventional cholecystectomy
      was performed instead. Perioperative blood loss of 7,300 ml was estimated. In
      total, the patient received 24 units of packed red blood cells, 12 units of fresh
      frozen plasma, and 12 units of platelets. After the operation, the patient was
      transferred to the surgical ICU for further observation. For 24 h at the ICU,
      blood pressure remained unstable, urine output decreased gradually, and scrotal
      and leg edema developed. Forty-four h after admission to the surgical ICU,
      arrhythmia and profound hypotension were noted and cardiac arrest ensued. After
      resuscitation for 2 h, the patient could not be revived and succumbed to
      cardiovascular decompensation secondary to acute renal shutdown and continuous
      retroperitoneal hemorrhage.

PMID- 9553243
TI  - Unexpected left endobronchial intubation in a case of Turner's syndrome.
AB  - Patients with Turner's syndrome present a multiplicity of cardiovascular and
      airway abnormalities. We describe a case of Turner's syndrome with pericardial
      effusion who experienced an inadvertent endobronchial intubation due to
      displacement of the endotracheal tube immediately after the pericardial drainage.
      A sudden increase of airway pressure and decrease of oxygen saturation in the
      presence of breathing sound audible via the chest piece placed on the left
      hemithorax first misled us to call our attention to sputum impaction. No sputum
      was obtainable from airway suction. Inadvertent bronchial intubation was highly
      suspected at the post-anesthesia room when a decrease of right side breathing
      sound was noted together with a progressive fall of oxygen saturation. Emergent
      chest x-ray confirmed the diagnosis. It was thought that the mishap took place
      early in the act of or following the pericardial drainage. Our case serves as
      evidence once again to emphasize the possibility of endobronchial intubation due
      to displacement of endotracheal tube during anesthesia and the importance of
      monitoring to guard against inadvertent bronchial intubation, particularly in
      patients with associated problems such as Turner's syndrome with huge pericardial
      effusion.

PMID- 9553244
TI  - A new device: Tube Securer. An endotracheal tube holder with integrated bite
      block.
AB  - Endotracheal intubation is the most commonly employed technique in airway
      management. Having an endotracheal tube (ETT) in place, however, does not
      guarantee a patent airway. Tube obstruction due to kinking, blood
      clots/secretion, dislodgment, or patient's biting can occur. These complications
      are life-threatening or even fatal. Employing a Guedel oral airway (OA) to act as
      a bite-block is a current common practice. However, with an OA in place does not
      necessarily prevent patient biting on the ETT. The author therefore proposed that
      this practice should have room for improvement and has made effort to design a
      new device for the purpose. The new dual function endotracheal tube holder with
      integrated bite-block as described can firmly secure the ETT in place and
      effectively prevent patient's biting on the tube. Therefore, it helps prevent the
      most serious complication of endotracheal intubation and subsequently improves
      patient safety.

PMID- 9553245
TI  - [Hydroxyethyl starch--an interim report].
AB  - Since the beginning of this century, a few biopolymers have been used as basic
      materials for volume substitution. Aside from gelatin and dextran, modified
      starch (hydroxyethyl starch, HES) is currently the first-choice means. Due to
      special manufacturing processes, different hydroxyethyl starches are now
      available. They have several different characteristics and produce different
      clinical effects. These clinical properties depend on the average molecular
      weight and the distribution of molecular weight as well as on the degree and
      pattern of substitution. The duration of volume effect, one of the most important
      parameters for the effectiveness of a volume substitute, depends to a large
      degree on the substitution. Elimination of HES from serum is delayed by a high
      degree of substitution and a high C2/C6 ratio of the substitution pattern. The
      molecular parameters of HES also influence other effects, such as cumulation in
      various organs and hemostasis. Critical reading of current HES literature shows
      that many questions still have to be answered. At the same time ways and means of
      optimizing differential volume substitution therapy and hemodilution therapy are
      emerging.

PMID- 9553246
TI  - [Introduction of patient-controlled analgesia--an interim report].
AB  - In spite of improved therapeutic methods, the number of patients who suffer from
      moderate or severe postoperative pain remains high at 30 to 70%. It is accepted
      that improvement of the organization of postoperative pain therapy is a necessary
      precondition for changing this situation. Therefore, patient-controlled analgesia
      (PCA) using pain-pumps should be recognized and the effect on the whole
      postoperative pain therapy of a university clinic observed. The authors report on
      the introduction of general therapeutic guidelines for the use of patient
      controlled pain-pumps. The recovery ward takes on a central role for both the
      beginning of pain therapy and the further care of the patient in various
      peripheral wards. It proved to be advantageous to use a bed-side protocol to
      document the programming of the pain-pumps and to register the pain-scores and
      side-effects. Because of these fundamental changes, the frequency of the
      application of pain-pumps increased six-fold within one year. Additionally, rapid
      pain treatment based on patients' needs increased clearly from 9.2 to 30.8%. The
      standardized introduction of PCA had an extremely favourable effect on the whole
      postoperative pain therapy and can thus be wholeheartedly recommended.

PMID- 9553247
TI  - [Ethics in preclinical emergency medicine--on the topic of medical futility and
      resuscitation efforts].
AB  - In prehospital emergency medicine, physicians are repeatedly faced with the
      question of when cardiopulmonary resuscitation (CPR) efforts should be withheld
      or terminated since they are clearly futile. Here, futile means the goal of
      saving life cannot be achieved. Determining futility involves qualitative und
      quantitative aspects. Does the possibility of simply restoring circulatory
      function justify the decision to initiate resuscitation or must the prospect of a
      prolonged meaningful life exist? The question of futility arises for the entire
      life-saving team during resuscitation efforts, for example, after traumatic
      cardiopulmonary arrest, prolonged down time, collapses in chronically-sick
      nursing home residents or during transport to hospital when prehospital CPR
      failed to restore spontaneous circulation. Possible solutions to this problem lie
      in restricting the objective of resuscitation to achieving a physiological effect
      in an organ system, i.e. regaining the cardiac pumping function, and in taking
      into account the chance of long-term survival and quality of life of the patient.
      Basically speaking, general ethical principles must be adhered to and these
      include consideration of a patient's right to self-determination. In the
      prehospital setting, however, the emergency physician is usually confronted with
      an unknown and unconscious patient and has no information about his preferences.
      In general, the patient's will to live and his desire for every effort to be made
      to save him can be assumed, even when there is only a slight chance of survival.
      Thus, unilateral decisions by emergency physicians to withhold CPR are only
      justified in special cases when it is obvious that CPR and preservation of life
      would not be in the patient's interest. When in doubt, resuscitation attempts
      must be made. The futility of these efforts may emerge later in hospital, or
      information becomes available regarding the patient's will which justifies an end
      to therapy.

PMID- 9553248
TI  - [Oxygen delivery, consumption and extraction in the acute period of burns in
      children].
AB  - Eighty-six children with burn injuries hospitalized in intensive care wards
      during the acute period of burn disease were examined. They were divided into 3
      groups: with involvement of up to 30%, 31-60%, and more than 61% of body surface.
      The children were examined during and after shock. The study was aimed at
      investigating the delivery, consumption, and extraction of oxygen in order to
      assess the criteria of disorders in the blood gas transporting system. In group 1
      these parameters were higher than normally during the acute period, reflecting
      the adequate reaction to burn injury. Therapeutic measures required volume
      support with infusion media. In the second and third groups these parameters were
      increased both during and after shock; for increasing oxygen transport, inotropic
      support was administered. In the third group oxygen delivery was within the norm
      which did not correspond to its consumption and, hence, respiratory support was
      needed.

PMID- 9553249
TI  - [The causes of and methods for correcting kidney functional disorders in newborns
      with surgical pathology].

PMID- 9553250
TI  - [General anesthesia using diprivan in patients with lesions of the locomotor
      system in a day hospital].
AB  - The study is aimed at investigating the possibility of using diprivan in total
      anesthesia of patients with consequences of infantile cerebral paralysis (ICP)
      during orthopedic surgery in an outpatient setting. The study was carried out at
      the Institute of Clinical Rehabilitology in the town of Tula. Ninety-two patients
      aged 4 to 15 years were examined. Hemodynamics was assessed by tetrapolar
      thoracic rheography after Kubecik. The patients were divided into 3 groups with
      disorders of static kinetic functions of different severity: I) walk-in patients,
      29.3%; II) patients walking with difficulty, 59.7; III) patients incapable to
      walk by themselves, 9.2%. The autonomic status was studied using clino
      orthostatic tests and cardiointervalography. Characteristic changes of the
      hemodynamics under conditions of narcosis and surgery were revealed in the
      patients with locomotor disorders of different severity. Diprivan can be used as
      the basic hypnotic component of anesthesia in orthopedic operations in patients
      with ICP consequences with locomotor disorders of different severity. It meets
      the requirements to the adequacy of anesthesiological protection in an outpatient
      setting. Assessment of the autonomic status in patients with ICP consequences
      permits a differentiated approach to total anesthesia with diprivan.
      Premedication with ketamine prevents the hypotensive effect of diprivan and
      ensures hemodynamic stability in the course of anesthesia and surgery.

PMID- 9553251
TI  - [Diprivan as a component of the anesthesia in emergency surgical interventions in
      children].
AB  - Sixty-seven children aged 5-15 years were induced to narcosis and narcotized with
      diprivan. The patients were operated on for appendicitis, peritonitis,
      osteomyelitis, phlegmons of different localization, and craniocerebral injuries.
      For induction, diprivan was intravenously injected in a dose of 3-4 mg/kg. During
      the main narcosis (central analgesia with fentanyl in a total dose of 0.008
      mg/kg/h) diprivan was infused by microjets in a dose of 6-9 mg/kg/h in
      combination with nitrogen oxide and oxygen in 1:1 ratio. Control group consisted
      of similar age-matched patients, to whom central analgesia without diprivan was
      administered. Respiration rate, heart rate, systolic and diastolic arterial
      pressure, mean arterial pressure (MAP), SaO2, and clinical course of anesthesia
      were examined at different stages of analgesia and surgery. During induction
      anesthesia the respiratory rate decreased by 27% and SaO2 decreased to 92.75 +/-
      1.2% due to the specific effect of diprivan. MAP decreased by 4.8%. During the
      traumatic moment of surgery, respiratory rate increased by 20.1%, SaO2 was 98.25
      +/- 0.24%, and heart rate increased by 22.6%. In the controls this period of
      surgery was associated with a more expressed reaction of the cardiovascular
      system, presenting as tachycardia (114.5 +/- 3.6) and increase of MAP by 10.1%.
      After anesthesia pain sensitivity returned earlier, due to which tachycardia and
      negligible hypertension were observed.

PMID- 9553252
TI  - [High epidural anesthesia in the correction of congenital heart defects with
      artificial circulation in children].
AB  - Effects of high thoracic epidural anesthesia (TEA) on hemodynamics were studied
      in patients undergoing cardiopulmonary bypass (CPB) surgery. In 7 patients aged 3
      7 years, TEA was used as an adjunct to standard oxygen-air-isoflurane anesthesia.
      We prefer using a combination of lidocaine with fentanyl for epidural anesthesia.
      Usually we take a loading dose of 4.5 mg/kg of lidocaine and 1 microgram/kg of
      fentanyl, which is followed after 40-50 min by 3.5 mg/kg lidocaine and 1
      microgram/kg fentanyl. TEA ensures good pain relief and hemodynamic stability and
      can be accepted as a safe and effective anesthetic technique in combination with
      inhalation anesthesia in children subjected to CPB.

PMID- 9553253
TI  - [Caudal epidural anesthesia in children operated on in the area of the
      lumbosacral segments].
AB  - Analgesia of children operated on the lumbosacral segments is discussed. Balanced
      total anesthesia was used with caudal epidural blocking by a combination of alpha
      2-agonist clofelin, local amide anesthetic bupivacaine, and narcotic analgesic
      promedol. Injection of a combination of clofelin (0.01% solution) in a dose of 1
      microgram/kg, standard dose of 0.25% bupivacaine solution with adrenaline
      (1:200,000) in a dose of 0.3 ml/kg, and promedol in a dose of 0.2 mg/kg into the
      epidural space via the caudal approach in the presence of superficial anesthesia
      with halothane (0.2-0.4 vol/%), nitrogen oxide and oxygen in 2:1 ratio ensured
      adequate analgesia and effective neurovegetative protection both during the
      operation and the first 25 h after it.

PMID- 9553254
TI  - [Regional anesthesias in children--the concept, advantages and general
      principles].
AB  - Validates the concept and discusses the advantages of central and peripheral
      regional anesthesias in children in combination with superficial narcosis during
      the stage of analgesia in surgical interventions of any severity. Emphasizes the
      efficacy of regional blocking, including prolonged ones, for postoperative
      analgesia. Presents the fundamentals of regional anesthesias in children.

PMID- 9553255
TI  - [Tracheal intubation in children using the benzyl isoquinoline-series
      nondepolarizing relaxants atracurium and mivacurium].

PMID- 9553256
TI  - [The characteristics of the action of nondepolarizing myorelaxants during
      operations on children with thermal injuries].
AB  - Effects of nondepolarizing myorelaxants pancuronium, arduan, and tracrium were
      studied during surgery in 347 children with thermal injuries aged from several
      months to 15 years. Nondepolarizing myorelaxants are drugs of choice for
      providing myoplegia in children operated on for thermal injuries. The optimal
      initial dose of these agents in children with burns is 30-50% higher than the
      recommended dose and depends on the size of the lesion. For controllable
      myoplegia, the doses of subsequent injections are to be 1.-5-2 times lowered in
      comparison with the initial dose. The effects of pancuronium and arduan depend on
      the hepatorenal function. Tracrium ensures sufficient controllable myorelaxation
      in children with burns even in cases with hepatorenal dysfunction.

PMID- 9553258
TI  - [Etran anesthesia in minor surgical interventions in children].

PMID- 9553257
TI  - [Central hemodynamic changes in children with locomotor system diseases during
      surgery and anesthesia].
AB  - Various neurovegetative reactions and disorders of circulation are observed in
      children with consequences of infantile cerebral paralysis (ICP). The
      manifestation of these reactions depends on the severity of motor disorders and
      the local painful syndrome. This study was aimed at detecting the changes in the
      central hemodynamics and development of measures preventing these changes during
      narcosis in patients with orthopedic consequences of ICP subjected to surgical
      treatment in an outpatient setting. In addition, we studied the possibility of
      wide use of calypsol in this category of patients in a one-day hospital.
      Autonomic reactivity was studied by cardiointervalography after Baevskii. The
      stroke and minute volume were assessed by tetrapolar thoracic rheography after
      Kubecik. A total of 120 patients aged 7-14 years with ICP consequences were
      divided into 3 groups with motor disorders of different severity. Examinations
      during preparation to narcosis and narcosis revealed a relationship between
      autonomic and hemodynamic disorders and the severity of motor disorders. An
      optimal method for preventing hemodynamic changes associated with narcosis in an
      outpatient setting is proposed.

PMID- 9553259
TI  - [The carbohydrate-energy metabolic and hemodynamic status of children with
      diffuse suppurative peritonitis in the early postoperative period].
AB  - Thirty-three children with grave peritonitis were examined 16-24 h after
      operation. The groups were matched for the hemodynamic status. Group 1 were
      patients with moderate hyperdynamic status, group 2 those with the extreme
      hyperdynamic status, and group 3--patients with hypodynamic status. The control
      group consisted of 36 healthy children subjected to herniotomy. Moderate
      hyperdynamic status was associated with balanced carbohydrate-energy metabolism.
      In the second group high levels of ATP+ADP+AMP and G6-PDH+6-PGDH activities and a
      decrease of ATP/ADP ratio and hypophosphatemia were observed. In the third group,
      low activity of the direct oxidative pathway and high activity of plasma LDH and
      hypophosphatemia were observed.

PMID- 9553260
TI  - [The effect of hemodilution on the indices of aerobic metabolism and water
      metabolism in children with congenital heart defects operated on under artificial
      circulation].
AB  - The majority of pediatric cardiosurgery centers make use of cardiopulmonary
      bypass (CPB) with low hematocrit, and therefore we deemed it interesting to
      investigate the pathological effects of hemodilution on patients. Specifically,
      we studied the effect of hemodilution on aerobic and water metabolism in children
      with congenital heart disease subjected to CPB. Two groups of patients were
      examined. In the studied group (n = 12, mean age 7.1 +/- 1.1 years) the blood
      fluid ratio in primary filling of the CPB device was 1:6.2 +/- 0.7 and minimal
      hematocrit during myocardial ischemia 18 +/- 0.7%. Control group consisted of 7
      patients aged 8.3 +/- 0.6 years, with the above values 1:2.8 +/- 0.4 and 22 +/-
      1.6%, respectively. The groups were similar as regards the initial status of
      patients, level of hypothermia, and duration of myocardial ischemia. Gas content
      in venous blood was the criterion of aerobic metabolism. Fluid accumulation in
      the extravasal space during and after surgery was assessed by bioelectroimpedance
      measurements of the total extracellular extravasal fluid (EEF). Monitoring showed
      a decrease of hematocrit during CPB to 18 +/- 0.7%, saturation of venous blood
      with oxygen within 70-75%, and oxygen content 37-43 mm Hg. In the main group a
      manifest increase of EEF was observed as early as during the early postperfusion
      period; this increase is probably one of the main components in the detrimental
      effect of hemodilution. Redistribution of fluid after CPB leads to expressed
      interstitial edemas and impairs the function of vital organs. That is why signs
      of cardiorespiratory failure were observed in the main group. Thus, one of the
      main problems in CPB with low hematocrit is fluid accumulation in the extravasal
      space.

PMID- 9553261
TI  - [The use of modified ultrafiltration in correcting complex congenital heart
      defects in newborn and nursing infants].
AB  - Modified ultrafiltration (MUF) was used in radical correction of complex
      congenital heart disease in 61 newborns and infants. The children were divided
      into 2 groups: group 1, 46 patients subjected to MUF, and group 2, 15 children
      operated on without MUF. Hemodynamic, hematological, biochemical, and
      immunological parameters were monitored. MUF in the newborns and infants helped
      adequately correct the hemohydrobalance due to ultrafiltration in the patient and
      hemoconcentration of the remaining volume in artificial ventilation device; it
      normalized the hematocrit values without additional infusion of donor blood.
      Elimination of inflammation mediators and cytokines recommends MUF for the
      treatment of newborns and infants.

PMID- 9553262
TI  - [The cardiac index dynamics of patients after the radical correction of tetralogy
      of Fallot depending on the level of the pressure-support ventilation (PSV)
      regimen].
AB  - Seventeen patients were examined, reoperated on for correction of Fallot's
      tetralogy on the open heart after a previous aortopulmonary anastomosis. Pressure
      support ventilation (PSV) was used in all patients during transfer to spontaneous
      pressure, making use of different levels of pressure support (20, 15, 13, 10, and
      8 mm H2O). Decrease of pressure support from 20-15 mm H2O to 13 mm H2O resulted
      in a sharp increase of cardiac index. We explain this phenomenon by a drastic
      increase of the respiratory volume during the use of high PSV levels (20-15 mm
      H2O), surpassing 1.5-2 times the physiological and age-specific norm; this leads
      to a sharp increase of the mean intrathoracic pressure, disturbing the
      cardiovascular function.

PMID- 9553263
TI  - [New potentials for monitoring the temperature and the relative and absolute
      humidity of the air-oxygen mixture during the prolonged artificial ventilation of
      newborn infants].
AB  - A new HTM-902 monitor (UCCP, Germany/Serviceinstrument, Russia) was used for
      continuous measurements of the temperature and relative and absolute humidity of
      inspired gas during prolonged mechanical ventilation in 86 neonates with
      respiratory failure caused by the respiratory distress syndrome (n = 42),
      meconium aspiration syndrome (n = 28), and congenital pneumonia (n = 16). All
      measurements were performed with a special probe connected to the inspiratory
      contour through a standard adapter close to the patient's T-piece. The monitor
      helped maintain the optimal values of the inspired gas conditioning during
      assisted ventilation of the neonates. The optimal relationships between gas
      temperature and humidity can be attained only with humidifiers with a
      servocontrol of temperature and heated wire inside the inspiratory circle tube.
      For maintaining adequate humidity of inspired gas after any changes in the
      ventilator flow rate or in the temperature inside the incubator, the heating
      power of the humidifier had to be corrected. However, even with servocontrolled
      humidifiers and humidity regulation, an increase of temperature inside the
      incubator over 35 degrees C made impossible the maintenance of the inspired gas
      humidity at the level of 96-100% with its temperature at the level of the
      patient's T-piece no higher than 37 degrees C.

PMID- 9553264
TI  - [The use of methods of assisted pulmonary ventilation in the weaning of children
      from ventilator breathing].

PMID- 9553265
TI  - [Parenteral nutrition: current concepts and methodological procedures].

PMID- 9553266
TI  - [Problems in the diagnosis of myocardial infarct in a newborn infant after acute
      severe intranatal asphyxia with the development of an organic CNS lesion].

PMID- 9553267
TI  - [A case of the successful treatment of subtotal pancreonecrosis in a 14-year-old
      child].

PMID- 9553268
TI  - [A case of the successful treatment of drug-induced toxic hepatitis in a child
      with tuberculous meningoencephalitis].

PMID- 9553269
TI  - [A case of severe poisoning by a methemoglobin-forming poison (saltpeter) in a 1
      month-old child].

PMID- 9553271
TI  - [Undesirable effects and complications after propofol anesthesia].

PMID- 9553270
TI  - [A case of the intravital diagnosis of a developmental defect of the
      bronchopulmonary system].

PMID- 9553272
TI  - Cultural divergence: Elie Metchnikoff's Bacillus bulgaricus therapy and his
      underlying concept of health.

PMID- 9553273
TI  - Kupat Holim, Dr. Isaac Max Rubinow, and the American Zionist Medical Unit's
      experiment to establish health care services in Palestine, 1918-1923.

PMID- 9553274
TI  - "Repeated disappointment": the Rockefeller Foundation and the reform of the Greek
      public health system, 1929-1940.

PMID- 9553275
TI  - The manuscript consultation reports of Francesco Torti.

PMID- 9553276
TI  - New approaches to the history of health and welfare.

PMID- 9553277
TI  - Looking for the answer.

PMID- 9553278
TI  - Influenza A outbreak on a cruise ship.

PMID- 9553279
TI  - A summary of the 1996-1997 Canadian FluWatch program.

PMID- 9553280
TI  - Verocytotoxigenic Escherichia coli infection in dairy farm families.

PMID- 9553281
TI  - Human isolates of Salmonella Typhimurium DT104 in Ontario.

PMID- 9553282
TI  - Influenza in Canada--1996-1997 season.

PMID- 9553283
TI  - Protocol for the investigation of acute flaccid paralysis and suspected paralytic
      poliomyelitis.

PMID- 9553284
TI  - Cytokine--intestinal epithelial cell interactions: implications for immune
      mediated bowel disorders.
AB  - The intestinal epithelial cell population is comprised of a dynamic continuum,
      ranging from undifferentiated, actively proliferating crypt cells, to mature
      absorptive villus enterocytes, lacking mitotic capacity. Under normal conditions,
      the constant loss of differentiated villus tip cells via apoptosis leads to a
      complete renewal of the epithelial cell population every few days. The
      physiological factors regulating enterocyte proliferation, maturation and
      apoptosis in health, as well as those that modulate these events in disease
      states remain largely unknown. It has been demonstrated in vitro that immature
      crypt cell proliferation is stimulated by factors such as TGF alpha and TNF
      alpha, whereas TFG beta and IFN gamma inhibit mitotic activity. Further studies
      showed that intestinal epithelial cells are able to produce and secrete several
      cytokines such as IL6, IL8, TNF alpha, TGF alpha and TGF beta, indicating the
      potential for autocrine and paracrine responses. A variety of immune mediated
      bowel disorders, including celiac disease, Crohn's disease and ulcerative
      colitis, are characterized by accelerated epithelial cell turnover and apoptosis,
      leading to altered crypt/villus morphology. There is increasing evidence that
      these changes, and the accompanying functional alterations of the bowel
      epithelium, are mediated by the cytokines released from infiltrating inflammatory
      cells, as well as from enterocytes themselves in an autocrine fashion.

PMID- 9553285
TI  - Gastrointestinal uptake of macromolecules.
AB  - Although the majority of dietary proteins undergo extensive digestion, small,
      nutritionally insignificant amounts of food proteins appear to cross the
      gastrointestinal mucosa intact. Experiments in a variety of allergic models has
      demonstrated that exposure of the gastrointestinal mucosa to the intact allergen
      leads to an anaphylactoid reaction. To examine the uptake of immunologically
      intact protein across the gastrointestinal epithelium, the mucosal to serosal
      movement of bovine serum albumin was measured in stripped gastric and intestinal
      mucosa mounted in modified Ussing-type chambers. Studies demonstrated that both
      gastric and intestinal mucosa are capable of actively transporting intact dietary
      proteins. In the intestine, the transport of intact molecules across the
      epithelium is a saturable, energy dependent process which utilizes the
      microtubular network and is regulated by the enteric nervous system. Transport
      across gastric mucosa is also dependent upon the microtubular network and is
      energy dependent.

PMID- 9553287
TI  - Rotavirus vaccines.
AB  - Encouraging results have been reported from several large trials of tetravalent
      rhesus rotavirus vaccine, with efficacy of 70-80% against severe disease. A
      recent Venezuelan study showed similar results to trials in USA and Europe. The
      vaccine may soon be licensed in USA. It provides the exciting prospect of a
      strategy to prevent one of the world's major child killers. Other candidate
      vaccines are under development including human-bovine reassortants, neonatal
      strains, non-replicating rotaviruses, vector vaccines and other genetically
      engineered products. Second and third generation rotavirus vaccines are on the
      horizon. The need for a rotavirus vaccine is well accepted by paediatricians, but
      public health authorities need to be lobbied. Other issues which need to be
      addressed include relative importance of non-group A rotaviruses, possible
      administration with OPV, the influence of breast feeding, and most importantly,
      cost. It is essential that rotavirus vaccine is somehow made available to all of
      the world's children, not just those in developed countries.

PMID- 9553286
TI  - Management of gastrointestinal food allergy in childhood.
AB  - Gastrointestinal food allergy in childhood is characterised by onset of
      gastrointestinal symptoms following food ingestion where the underlying mechanism
      is an immunologically mediated reaction within gastrointestinal tract.
      Presentation may be quick, slow or quick and slow after food ingestion. Diagnosis
      depends on response to food elimination, response to food challenge and analysis
      of response to food elimination. Management centres upon an elimination diet, the
      need for this is temporary. Cow's milk protein hydrolysates or amino acid
      formulae are preferred to soy formulae.

PMID- 9553288
TI  - Pathophysiology of growth retardation in chronic renal failure.
AB  - Data concerning the transcription of growth hormone and the various interactions
      between growth hormone/insulin-like growth factor (IGF) axis in uremia, acidosis
      and nutrition are presented. The recent evidence of tissue resistance to growth
      hormone in uremia provided the medical rationale for the use of growth hormone in
      chronic renal failure. The growth hormone receptor resistance in uremia and the
      decreased IGF-I by acidosis are additional rationale for the use of growth
      hormone. New findings of how acidosis causes the reduction of IGF-I expression at
      the growth plate of the long bone and the significant proteolysis after even
      small changes in serum bicarbonate content are presented to provide the
      pediatrician with an overview of these recent advances.

PMID- 9553289
TI  - Serum HDL level at acute stage of Kawasaki disease.
AB  - Kawasaki disease is a disease of acute vascular inflammation of unknown etiology
      and HDL is a known risk factor of vascular damage. So far, there is no specific
      serum marker for KD. The previous study has shown a remarkable change of serum
      HDL in the patients with KD. To find whether changes in serum HDL level is a
      specific serum marker for early diagnosis of KD, we measured the concentration of
      HDL, LDL, TC, TG and CRP immediately after admission and one week later in three
      groups of patients (56 patients with KD, 38 patients with clinical viral
      infection, and 42 patients with bacterial infection). There was a significant
      decrease of HDL and increase of TG immediately after admission in three groups of
      patients. HDL and TG did not return to normal one week later. HDL level is more
      adversely affected in severe diseases than in mild diseases. Our results
      indicated that low HDL level is noted in various acute infection and is not a
      specific serum marker in the early stage of Kawasaki disease. It is interesting
      that low HDL is a universal phenomenon in this series. Further research is needed
      to explain the mechanism of lipid alterations and its consequences.

PMID- 9553290
TI  - A survey on the treatment strategy of patent ductus arteriosus in very low-birth
      weight infants.
AB  - This study is a retrospective analysis of the clinical data of 67 very low birth
      weight infants (VLBWI) with symptomatic patent ductus arteriosus (PDA); all were
      admitted to four neonatal intensive care units (NICU) from January 1, 1996
      through December 31, 1996. The mean gestational age was 27.9 +/- 2.4 weeks, the
      mean birth weight was 1078 +/- 193 g. Fifty-six infants (83.6%) had RDS, and 53
      infants (79%) received artificial surfactant. The NICU at a regional hospital
      used CVD score > or =3 as the sole criteria and the remaining three NICUs used
      color Doppler echocardiogram to confirm a symptomatic PDA and to treat it;
      sometimes LA/AO > or = 1.3 was used as the criteria for indomethacin treatment.
      Two of these three hospitals sometimes used the pulsed Doppler echocardiogram as
      well as color Doppler examination as the treatment criteria. Seven infants
      (10.5%) had contraindication for indomethacin treatment; four of them closed
      after conservative treatment, and another three were subjected to surgical
      ligation. Of the remaining 60 infants, 3 were treated with oral indomethacin and
      57 were treated with intravenous indomethacin. The mean age when initial
      treatment given was 3.8 +/- 1.5 days (range, 8 hours approximately 20 days).
      Among them 10 (16.7%) were within 24 hours after birth, 25 (41.7%) were between
      24 and 48 hours, and 25 (41.7%) were beyond 48 hours. The dosage of indomethacin
      was 0.2 mg/kg per dose intravenously every 12 to 24 hours for three doses as a
      full course, if not contraindicated. The mean dose of indomethacin was 2.8 +/-
      1.5; 10 infants (16.7%) received 1 dose, 15 (25%) received 2 doses, 27 (45%)
      received 3 doses, 3 (5%) received 4 doses and 5 (8.3%) received 6 doses. Among
      them, 51 infants (85%) PDA closed (including 2 treated with oral indomethacin), 9
      (15%) failed to close and 6 of them received surgical ligation (including 1
      treated with oral indomethacin). The complications associated with indomethacin
      treatment were hypoglycemia (52%), decreased urine output (42%) and
      gastrointestinal hemorrhage (32%). The infants with RDS had an earlier mean age
      of initial treatment than non-RDS infants (3.3 +/- 2.5 vs. 7.6 +/- 5.6 days; p <
      0.05), and also had a higher closure rate (89% vs. 57%; p < 0.05). There was a
      closure rate of 85% in this multicenter retrospective analysis. Even though the
      infants received only one or two doses, they still had a good chance of ductal
      closure (21/25, 84%). To minimize the complications associated with indomethacin
      treatment in VLBWI, the protocol of indomethacin treatment should be re
      evaluated.

PMID- 9553292
TI  - The role of percutaneous renal biopsy in the diagnosis and management of renal
      diseases in children.
AB  - We undertook a retrospective study to determine the proportion of patients in
      whom diagnostic and therapeutic changes were made as a result of renal biopsy.
      From April 1992 to March 1997, 111 renal biopsies were performed on 109 children
      aged 11 months to 18 years at our hospital. Adequate renal tissue was obtained in
      106 cases (95.3%). Gross hematuria was observed in 12 cases (10.8%). Perirenal
      hematoma was found in 8 cases (7.2%) by ultrasound. A scoring system was designed
      to assess if diagnosis and therapy are affected as a result of renal biopsy. For
      diagnosis, the score was 0 when no additional information was obtained; 1 when
      the diagnosis was confirmed or ruled out; and 2 when the diagnosis was changed
      after biopsy or the pathologic findings provided a definite prognosis. For
      therapy, the score was 0 when the management was not changed after biopsy; 1 when
      the clinical diagnosis was confirmed and yielded a change in management; and 2
      when the diagnosis and management were changed after biopsy. We found the benefit
      score for diagnosis was 0 in 2 (1.9%) of the 106 biopsied cases; 1 in 78 (73.6%),
      and 2 in 26 (24.5%). The benefit score for therapy was 0 in 62 (58.5%); 1 in 24
      (22.6%); and 2 in 20 (18.9%). Therapeutic change always occurred in the biopsied
      patients with steroid resistant nephrotic syndrome and systemic diseases with
      renal involvement, and occasionally occurred in frequent relapsing nephrotic
      syndrome, steroid dependent nephrotic syndrome and asymptomatic proteinuria plus
      hematuria. It never occurred in patients with acute or chronic renal failure and
      hematuria. We conclude that renal biopsy is a safe and efficient procedure in
      pediatric patients. It can markedly change diagnosis and therapy, and can
      increase the likelihood for a more rational management of children with renal
      disease.

PMID- 9553291
TI  - Evaluation of a live attenuated varicella vaccine in 15- to 18-month-old healthy
      children.
AB  - A clinical trial was conducted in Taiwan in 15- to 18- month-old healthy children
      to study the reactogenicity and immunogenicity of live varicella vaccine combined
      with standard measles-mumps-rubella vaccine. A total of 118 varicella antibody
      negative children were enrolled. They received one dose of varicella vaccine and
      one dose of measles-mumps-rubella vaccine at the same time. The vaccines were
      well tolerated; adverse reactions were mild and infrequent, with 2% of vaccines
      developed skin rash. No vesicular rash was seen. Concomitant varicella
      vaccination did not significantly increase the incidences of reactions associated
      with MMR vaccine. The seroconversion rates to varicella, measles, mumps and
      rubella all approached 100%. This study confirmed that simultaneous
      administration of live attenuated varicella vaccine and MMR vaccine was safe and
      immunogenic in healthy young children in Taiwan.

PMID- 9553293
TI  - Holocord intramedullary spinal cord astrocytoma: report of one case.
AB  - Intramedullary spinal cord astrocytoma in infants is relatively uncommon. Its
      occurrence is usually confined to the cervical and cervicothoracic regions. In
      this paper, we report on the case of a 4-month old male infant with low grade
      holocord intramedullary spinal cord astrocytoma. He had developed progressive
      weakness of the lower extremities over a month period. Neurological examination
      revealed flaccid paraplegia as well as complete loss of all modalities of
      sensation below the T10 level. MRI revealed a large intramedullary mass which was
      found to be an intramedullary astrocytoma at surgery. This case report presents
      the clinical features, radiographic findings, and treatment and outcome for this
      patient together with a review of relevant literature.

PMID- 9553294
TI  - Absolute ethanol embolotherapy for hemangioma with Kasabach-Merritt syndrome.
AB  - This report describes a female baby having a hemangioma over the right thigh that
      had appeared as an irregular bruise since two days old. Severe thrombocytopenia,
      consumptive coagulopathy, anemia, and heart failure developed at three months
      old. With a diagnosis of Kasabach-Merritt syndrome, systemic corticosteroid,
      vincristine, subcutaneous alpha-interferon, and massive plate transfusion were
      given. However, the platelet count remained low and the skin lesion enlarged
      gradually. Trans-feeding-arterial embolotherapy with a 5 ml pure ethanol (1
      ml/kg) injection was performed at four months of age. Thirty days later, her
      platelet count recovered and the hemangioma shrunk in size. This case illustrates
      that absolute ethanol embolotherapy is an effective treatment for hemangioma with
      Kasabach-Merritt syndrome and may be life-saving for those with lesions
      refractory to medical therapy.

PMID- 9553295
TI  - Pneumonia with pneumatocele formation caused by Mycobacterium tuberculosis:
      report of one case.
AB  - Pneumatoceles are usually characteristic of staphylococcal pneumonia. They are
      rarely formed as one of the complications of Mycobacterium tuberculosis
      pneumonia. We report a 1-year-and-5-month old male child with pneumonia who was
      confirmed to have the rare complication, pneumatocele formation, by chest
      radiography and computed tomography. Since the patient did not respond to empiric
      antibiotic therapy, gastric larvage through a nasogastric tube was performed on
      three consecutive mornings and, as a result, acid fast rods were found on the
      three specimens. The cultures subsequently yielded M. tuberculosis. He was
      finally cured with a 6-month course of antituberculous chemotherapy. We conclude
      that tuberculosis should be considered in infants or young children with
      pneumonia that presents radiologically as pneumatocele formation, especially in
      whom there has been no response to empiric antibiotic therapy.

PMID- 9553296
TI  - Pneumococcal meningitis complicated with hemolytic uremic syndrome: report of two
      cases.
AB  - Hemolytic uremic syndrome (HUS) in associated with infections of neuraminidase
      producing streptococcus pneumoniae was rarely reported in the literature. We
      report two infants with proven pneumococcal meningitis associated with anemia,
      thrombocytopenia, renal failure, and T-antigen activation characteristic of
      neuraminidase activity. This supports a common pathogenesis in HUS following
      infection of neuraminidase-producing strains of S. pneumoniae. One infant
      complicated with status epilepticus died, and the other infant survived without
      sequelae. We recommend that neuraminidase production should be considered in case
      of pneumococcal meningitis associated with anemia and thrombocytopenia without
      diffuse bleeding tendency. Early recognition of HUS associated S. pneumoniae
      neuraminidase production is vital. The use of compatible washed red blood cells,
      meticulous supportive care and appropriate use of dialysis will improve survival.

PMID- 9553297
TI  - Congenital myopathy with uniform type 1 fiber predominance and type 2 fiber
      hypoplasia: report of one case.
AB  - A 2-month-old female infant, presented with frequent choking and cyanosis during
      feeding, and poor sucking capability since the age of 45 days. Growth retardation
      with body weight and length below the third percentile, and head girth below the
      tenth percentile, were noted on admission. Generalized hypotonia, mild proximal
      muscle weakness and diminished tendon reflex were also noted. A biopsy from the
      left quadriceps femoralis showed uniform type 1 fiber (90%) predominance, and a
      decrease in fiber size and number of type 2 fibers. A biopsy from her father
      revealed uniform type 1 predominance (99.8%) and 30% central nuclei change. The
      course of her illness was rather short, and the patient has developed normally
      since the age of 4 months. Significant improvement in muscle strength and normal
      intelligence were observed after 3 years of clinical follow-up.

PMID- 9553298
TI  - [Anaphylactic shock. Diagnosis-therapy--emergency measures].
AB  - Anaphylaxis is an immediate, life-threatening, general allergic reaction mediated
      by bioactive substances released by mast cells. Symptoms include diffuse
      urticaria, gastrointestinal disorders (sensation of fullness, diarrhea and
      abdominal cramps), bronchospasm, edema, airway obstruction, hypotension,
      cardiovascular collapse, and even death. The present review discusses the
      adequate diagnostic and therapeutic management based on our own experience.

PMID- 9553300
TI  - [Hand on the heart: adequate experience is mostly absent. "Dry runs" are still
      not real emergencies].

PMID- 9553299
TI  - [Allergy test in general practice--yes or no?. Interview by Beatrice Wagner].

PMID- 9553302
TI  - [Skin manifestations in Lyme borreliosis. 6: Acrodermatitis chronica atrophicans
      (ACA)].

PMID- 9553301
TI  - [Allergies in general practice are too infrequently diagnosed].

PMID- 9553303
TI  - [New herpesviruses HHV 6, 7 and 8 and their clinical significance].

PMID- 9553304
TI  - [Amantadine--a new option in chronic hepatitis C?].

PMID- 9553305
TI  - [Recommendation for rehabilitation measures of elderly disabled patients by the
      medical service of hospital insurance in Berlin and Brandenburg].
AB  - According to the German Nursing Care insurance law (Pflegeversicherungsgesetz)
      experts of the Medical Advisory Board of the statutory sickness funds
      (Medizinischer Dienst der Krankenversicherung, MDK) must consider recommending
      rehabilitative measures for persons in need of nursing care. This study measures
      the proportion of proposed rehabilitative therapies (physiotherapy, ergotherapy,
      speech therapy) as well as clinical and non-clinical predictors for these
      recommendations. The study population of the cross-sectional study consisted of
      all persons aged 60 years and older in Berlin and Brandenburg for whom the MDK
      experts had diagnosed a need for nursing care (stages I to III) by means of home
      visits in the second half of 1995. Data on recommendations and potential
      predictors were taken from the expert records. Recommendation rates were 6.6%
      (physiotherapy), 0.7% (ergotherapy) and 0.8% (speech therapy) respectively, for
      Berlin and Brandenburg taken together. While clinical variables (impairments and
      disabilities) had a considerable impact on the recommendations, also non-clinical
      variations were noted. Physiotherapy recommendation rates differed 3-fold by
      region (Brandenburg: 10.3%; Berlin: 3.4%). Variations also existed for age (60-70
      years: 10.7%; > 90 years: 2.5%) and the presence of a professional care
      institution (present: 8.6%; not present: 5.4%). The strongest effect had an
      already existing prescription of physiotherapy from the patient's physician
      (current physiotherapy: 23.5%, no current physiotherapy: 4.6%). Multiple logistic
      regression demonstrated that these variables had independent effects after
      accounting for their overlapping influences and clinical characteristics.
      Variations of physiotherapy recommendation rates were also found for profession
      of the MDK experts (physician: 5.9%; nurse: 9.2%; physician and nurse together:
      7%), but the effects were only partially independent. The observed low rates of
      recommended physiotherapy, ergotherapy and speech therapy as well as the non
      clinical variations question the appropriateness of current recommendation
      practices.

PMID- 9553306
TI  - [Patient satisfaction after inpatient rehabilitation: different results at
      different follow-up times?].
AB  - Different Results at Different Times of Questioning? In 1994 a quality assurance
      programme for the German medical rehabilitation system was introduced by the
      national association of pension funds. One of its five parts focussed on
      patients' satisfaction and health effects. Both domains were to be assessed by
      postal questionnaires. The first section of the instrument enquired about
      patients' perceptions and evaluations of both rehabilitation structures and
      processes. It is well known that satisfaction surveys tend to underestimate the
      true level of criticism due to social desirability bias. This is especially
      problematic in the context of quality assurance programmes where criticism can be
      seen as one driving force of improvement. The magnitude of the bias depends on
      many factors. In this study we tested the influence of different time intervals
      between discharge from rehabilitation clinic and first postal contact. DESIGN: We
      conducted an experimentally varied satisfaction survey among four groups of
      rehabilitands. If necessary, the first postal questionnaire was followed by two
      reminders. SETTING: One Bavarian pension fund for blue collar workers. PATIENTS:
      520 rehabilitands were recruited from various rehabilitation clinics specialized
      in muskuloskeletal disorders. About 70% suffered from nonspecific back pain. They
      were randomly allocated to one of the following time intervals between discharge
      and postal questionnaire: one, four, eight and twelve weeks. INSTRUMENTS AND
      TARGET VARIABLES: All patients received an identical questionnaire with 67 items
      and several subscales. We compared the extent of dissatisfaction between the four
      groups. RESULTS: The response rate (after two reminders) showed a linear decrease
      from 97% (postal questionnaire after one week) to 83% (12 weeks). The extent of
      dissatisfaction did not change systematically though there was a (statistically
      nonsignificant) tendency towards higher levels of criticism at week twelve.
      CONCLUSIONS: An experimental variation of time intervals between discharge from
      rehabilitation and first postal contact does not seem to influence the extent of
      reported dissatisfaction though it clearly influences the response rate: The
      later the sending out the lower the response rate. Taking into account additional
      administrative and organisational aspects of the programme we propose to send out
      satisfaction questionnaires between 8 and 10 weeks after rehabilitation.

PMID- 9553307
TI  - [Significance of social medicine in the medical contract office].
AB  - In the German statutory social security system, the necessity of long-term care
      for chronically ill persons with multi-morbidity and reduced performance has made
      the socio-medical management of illness and its consequences an important
      characteristic of primary medical activity. In routine practice a discrepancy
      between the practical demands and social-medical insights has often been
      observed. With this in mind, the aim of our pilot study was to systematically
      collect data on the state of the art and attitudes towards the relevant spheres
      of work in a defined group of physicians and analyse this data. The study was
      carried out in the form of a voluntary questionnaire within the medical
      association (Arztlicher Kreisverband-AKV) in the area of Erlangen-Hochstadt. The
      database was a computer-processible, anonymous questionnaire with which first of
      all general socio-demographic and activity-related data was collected. The
      following 10 questions included, in addition to an estimation of the
      participants' own socio-medical knowledge, questions on the general status of
      socio-medical knowledge and how the individual gained this knowledge and the
      importance of socio-medical themes in routine practice. The data was evaluated
      using descriptive statistics in the form of exploratory data analysis. Of the 320
      physicians registered at the time of the investigation (4/96), 89 (31 female
      doctors, 58 male doctors) sent back a questionnaire that proved useful (returns:
      approx. 28%). Significant sex-related or specialisation-related differences with
      regard to participation in the study were not observed. The ratio of female to
      male doctors and of general practitioners to specialists in the study collective
      corresponded more or less to the distribution in the total group. The
      participants had a median age of 41 years (minimum 31, maximum 71) and had been
      in practice for a median of 11 years (maximum 43 years, minimum 1 year). 36% were
      general practitioners, 64% specialists. 97% regarded sound knowledge in socio
      medicine as essential for doctors wishing to set up practice. 70% regarded their
      own knowledge of socio-medicine as being in need of improvement. 85% regarded
      their knowledge as having been insufficient at the start of their medical
      careers. With regard to doctors gaining socio-medical competence, routine
      practice and their own autodidactic capabilities played an important role. 84%
      would like to see increased teaching of socio-medical themes during specialist
      training courses. For over 70% socio-medicine is a part of medical studies as a
      subject in its own right. The content and aims of New Public Health were known to
      45%. Among the areas of socio-medical work the care of chronically ill persons
      was given highest priority. Preventive measures were also accorded high relevance
      by the participants, and they were particularly interested in preventive
      medicine. Taking into consideration conceptional problems (e.g. the size of the
      random sample/selection effects) it was found that: despite many years of
      practice in some cases, doctors feel there is a deficit in their socio-medical
      knowledge--prcctical knowledge is mainly gained autodidactically during routine
      practice ("learning by doing"). There is a clear wish for increased consideration
      of socio-medical themes in specialist training courses. The great importance of
      socio-medical tasks as part of medical practice is undeniable to the study
      collective. The results underline the necessity for improved communication and co
      operation between doctors involved in primary medical activity and in socio
      medicine.

PMID- 9553308
TI  - [Social psychiatry aspects of alcoholism: epidemiology, treatment structures and
      recent results of therapy research].
AB  - In Germany the per capita consumption of alcohol has tripled since World War II
      with a slight decrease in recent years. The number of alcoholics has been
      estimated between 2.5 mill. and 10 mill. Epidemiological studies suggest a 6
      month prevalence rate of 3.1% (USA 2.9%): 10.4% in males, 0.8% in females; Life
      time prevalence estimates range up to 13%. More recent findings also suggest that
      alcoholism in adolescents is an increasing problem. The resources for treatment
      of alcoholism are limited: Only 1% of all alcoholics are treated in special
      addiction rehabilitation programmes, whereas the majority of patients are treated
      by their physician, in a general hospital or not at all. Approximately 30,000
      patients are treated in special clinical rehabilitation programmes per year.
      Socioeconomic consequences of alcoholism have not been evaluated in detail; some
      cast models are discussed. In recent years both day-hospital and outpatient
      rehabilitation programmes for alcoholics have been established but few
      catamnestic studies have been conducted so far. The possible benefit of new
      antidipsotropic agents (so-called anticraving drugs) must also be examined in
      greater detail. Catamnestic findings and the outcome of treatment studies are
      discussed.

PMID- 9553309
TI  - [Pyrethroids in house dust of the German housing population--results of 2
      nationwide cross-sectional studies].
AB  - As a part of the German Environmental Surveys performed in 1985/86 (West
      Germany), 1990/91 (West Germany) and 1991/92 (East Germany), dust samples were
      collected in the households of about 1600 randomly selected adults (25 to 69
      years) and an analysis of these samples was performed in respect of their content
      of 8 different pyrethroids and of the synergist piperonyl butoxide (PBO). In the
      1990-92 survey about 90% of the samples contained permethrin in concentrations
      above the limit of quantification. This showed permethrin to be the most
      widespread of the 8 compounds investigated. The geometric mean of the permethrin
      content in domestic dust was 0.22 mg/kg. Only about 8% of the samples contained
      one or more of the other investigated substances (cyfluthrin, lambda-cyhalothrin,
      cypermethrin, alpha-cypermethrin, deltamethrin, empenthrin, d-phenothrin) in
      quantifiable amounts. About 76% of the samples contained quantifiable amounts of
      PBO. In East Germany the geometric mean of the PBO content (0.21 mg/kg) was
      significantly higher than in West Germany (0.07 mg/kg), but no difference for
      permethrin was found. Significant associations could be shown for the permethrin
      content and the application of biocides as well as for the PBO content and
      regional factors (size of community, type of dwelling area). Samples collected in
      1985/86 (West Germany) showed a geometric mean for permethrin of 0.06 mg/kg and
      for PBO of 0.07 mg/kg. Comparing the values of 1985/86 and 1990/91, a significant
      increase can be observed for permethrin, whereas the PBO concentration remained
      constant.

PMID- 9553310
TI  - [Snack breaks in primary and vocational schools of the Rems-Murr district].
AB  - The aim of this study was to collect data on catering at break in primary schools
      as a basis for planning health promotion activities. To meet this aim the
      principals of all schools were interviewed and the snacks and drinks that were
      sold at break were recorded in a checklist. The results show, that in 27.4% of
      the schools snacks or drinks were sold that cause damage to dental health or are
      not recommended for general health. Moreover nutritious products as school milk,
      wholemeal bread and fruits were frequently not available. In 55.8% of the schools
      no snacks and in 37.3% of them no drinks were sold at all. In 51% of the schools
      the children had the opportunity to have breakfast together in the classroom. The
      selling of not recommended snacks and drinks should be banned from schools,
      because they rather make healthy choices more difficult than easier and therefore
      undermine the effectiveness of health education. To change eating habits
      continuous and long-standing activities concerning breakfast at school are
      recommended.

PMID- 9553311
TI  - [Thyroid hormone level in children in the area of a toxic waste incinerator in
      South Essen].
AB  - As part of an environmental epidemiological study on potential exposure to a
      toxic waste incineration we investigated whether children in an area with a toxic
      waste incinerator (TWI) have different levels of thyroid hormones than children
      in two comparative regions. The TWI region is situated in the Rhine valley (about
      30 km across) with low mountains on both sides. Other industries such as a
      chemical plant are nearby, and several municipalities are located in the
      environment of these. One comparative area 20 km north is also industrially and
      agriculturally used, but has no incinerator (Rhine Valley comparison group, RVC
      group). South-East of the incinerator region in an area of low mountains (about
      400 m high) we investigated the second comparison group (Odenwald comparison
      group, OWC group). Altogether 671 children from 18 municipalities participated in
      1994/95 (participation 61.5%). Blood samples were taken from 341 children, aged 7
      to 10 years, living in non-smoking households or in households with only light
      smokers. Serum levels of thyrotropin stimulating hormone (TSH), free thyroxine
      (FT4), and free triiodothyronine (FT3) were analysed. In a self-administered
      questionnaire for the parents, which was checked during the medical examination,
      we gathered information on age, gender, passive smoking, consumption of fish, as
      well as use of wood preservatives and pesticides at home. By means of adjusted
      regression analysis the first step was to check whether the TWI group had means
      of TSH, FT4 and FT3 that differed from the OWC group and the RVC group. If
      differences were at least marginally significant, the second step was to analyse
      whether children from different municipalities had statistically different mean
      values and if the pattern of these municipalities fitted into the three regions.
      For the latter, children from a town in the Odenwald served as comparison group.
      The TWI group had statistically significantly (p < or = 0.05) reduced FT3 and FT4
      values with a higher prevalence of FT3 values below clinical references (TWI
      group: 7.7%, RVC group: 3.2%, OWC group: 1.2%). Children from four out of nine
      TWI municipalities showed statistically significantly lower FT3 means than
      children from the reference town, and one of the seven municipalities from the
      comparative areas. The mean FT4 was significantly lower in four municipalities of
      the TWI area and in one of the two other areas. The mean TSH was only marginally
      different, mainly influenced by gender differences with boys having higher TSH
      levels. Comparison of the municipalities did not reveal a consistent pattern.
      Industrial pollution might influence the regulatory system of the pituitary
      thyroid axis. Reduced peripheral thyroid hormones associated with exposure to
      polychlorinated biphenyls (PCB) and dioxins/furans (PCDD/F) were found in
      previous studies. Our results suggest that children exposed to toxic waste
      incineration in their environment have lower thyroxine and triiodothyronine
      levels.

PMID- 9553312
TI  - [Evaluation of scientific publication: a recommendation (not only) for general
      medicine].
AB  - A Proposal (not only) for General Practice/Family Medicine: Medical faculties and
      other institutions increase their pressure on scientific societies and colleges
      to present and set standards to evaluate publications from their discipline.
      After discussing the quality of different literature and publication indices the
      authors take a critical look at the impact factor which arouses much controversy
      among medical faculties. The evaluation standard presented for general practice
      comprises three categories of quality to which (A) Top Journals, (B) Standard
      Journals and (C) other Journals (but also books and book contributions) are
      allocated. Assessment criteria are mainly based on indexation (Index Medicus) and
      independent peer review. Within that system original papers are valued higher
      than reviews and editorials or comments. The impact factor is not considered to
      be helpful for judgement. The authors are convinced that any numerical point
      system would not be likely to lead to a reasonable assessment of an individual
      publication. Furthermore, there could be an increased risk that members of
      committees would prefer the point system for their judgement rather than to read
      papers in detail. The suggested standard could serve as an aid for referees from
      disciplines other than general practice. However, their expert decision regarding
      the quality of publications could not be replaced by even the most sophisticated
      valuation system.

PMID- 9553313
TI  - [Excessive reactions in Mendel-Mantoux tuberculin tests].

PMID- 9553314
TI  - [Infiltrating lobular carcinoma of the breast. Clinical picture, treatment and
      prognosis].
AB  - An analysis of 80 patients with infiltrating lobular carcinoma of the breast
      treated at Center of Oncology in Krakow is presented. All patients underwent
      radical mastectomy. The evaluation of treatment results showed stage,
      pathological tumor size, and involvement of axillary nodes as the prognostic
      factors. The ten-year survival rate NED in all group was 38.8%; for stage I, II,
      and III it was 62.5%, 48.8%, and 19.4% respectively.

PMID- 9553315
TI  - [Suture of the episiotomy wound--comparison of two techniques from clinical and
      cosmetic aspects].
AB  - The use of an episiotomy for vaginal delivery is a controversial topic in modern
      obstetrics. If one is done, however, correct technique of perineal trauma repair
      is important. The usual episiotomy has traditionally been closed with interrupted
      suture. The use of a less reactive material, e.g. polyglycolic acid (Dexon), seem
      to be suitable for subcutaneous skin closure and beneficial in terms of acute
      postpartum discomfort and healing. The comparison of healing and patient comfort
      parameters between interrupted and subcutis polyglycolic acid suture used for
      episiotomy repair after delivery was done. Patients had follow-up during hospital
      stay, and two months after delivery a self administered questionnaire was sent to
      all women who participated, enquiring about perineal pain, resumption of sexual
      intercourse and cosmetics of suture line. Of 52 patients who had repair with
      interrupted suture, 21 were lost to follow-up. Of 65 gravidas who had repair with
      subcutis suture, 23 were lost to follow-up. At the 3rd day postpartum
      examination, patients with subcutis sutures had significantly better healing. An
      inflammatory process was present in 2 of 52 patients with interrupted sutures
      comparable with 1 of 65 in the subcutis group, and a gaping wound in 0 of 52 and
      1 of 65, respectively. Recovery of function, measured by resumption of sexual
      activity by 8 weeks, was demonstrated in 5 of 31 patients with interrupted
      sutures versus 24 of 42 patients who had subcutis sutures. Episiotomy repair with
      subcutis polyglycolic acid (Dexon) offers significant advantages over traditional
      interrupted suture, both in terms of wound healing and resumption of sexual
      activity.

PMID- 9553316
TI  - [Glycosaminoglycans in uterine leiomyoma].
AB  - During development of leiomyoma, a reorganisation of main components of
      connective tissue has been found. All types of glycosaminoglycans are present in
      this tissue. Among them the heparan sulphate is the most abundant. Its content
      was found to increase with uterine myoma weight. It is worthy of note that the
      increase of keratan sulphate is observed in big leiomyoma.

PMID- 9553317
TI  - [Creatine kinase activity ec 2.7.3.2 in blood serum of women during pregnancy and
      during delivery].
AB  - In the serum of women during the pregnancy and during the stages of the delivery
      the activity of creatine kinase (CK) was measured using the test by Fermognost.
      The investigations were led in three 20-personal groups of women: non-pregnant,
      pregnant examined three times, in each trimester of pregnancy, and labored women
      examined three times, one time in each stage of delivery. The age of investigated
      women was between 18-39 years. According to obtained results, it was noticed
      statistically significant increase in the activity of this enzyme during the
      pregnancy. Measuring the activity of creatine kinase in three stages of delivery,
      the highest increase in this enzyme activity was observed in the third stage.

PMID- 9553318
TI  - [Estimated levels of fructosamine in venous blood of pregnant women and in cord
      blood].
AB  - In the study there was estimated maternal (Fm) and cord blood (Fc) fructosamine
      levels in 151 diabetic (58 PGDM and 93 GDM) and 100 control subjects on the day
      of delivery. It was found that Fm and Fc levels in PGDM and GDM groups were
      significantly higher than in the control group. It was also found the
      significantly positive correlation between Fm and Fc levels in all study groups.
      It leads to the conclusion that pregnant diabetic women and their fetuses were
      hyperglycemic during the last 2 weeks of pregnancy. Our results indicate that on
      the basis of maternal fructosamine levels it is possible to apply on indirect
      estimation of metabolic status of the fetus.

PMID- 9553319
TI  - The application of GnRH analogues in the treatment of uterine myomas in
      perimenopausal women.
AB  - Our objective was to determine whether long GnRH agonists induce effective and
      persistent shrinkage of uterine myomas in perimenopausal women, as well as to
      determine the usefulness of Doppler sonography study in evaluating the therapy
      benefit. The study covers 30 patients with symptomatic myomas in perimenopausal
      period. We used long GnRH agonist-Decapeptyl (Ferring) at 28 days intervals in
      the course of 4 months. After discontinuing the application of Decapeptyl,
      medroxyprogesterone acetate was introduced for 6 months. The GnRH/gestagens
      therapy is useful and effective in treatment of symptomatic myomas in
      perimenopausal patients, and may be a valid alternative to hysterectomy. Doppler
      sonography is reliable in monitoring of uterine circulation in patients under
      GnRH therapy.

PMID- 9553320
TI  - [Stromal sarcoma of the uterus in an 18-year old girl].
AB  - The authors describe diagnostic difficulties connected with proper estimation of
      stromal sarcoma biological activities, which developed in uterus corpus in 18
      year old girl previously treated with hormones, because of irregular painful
      menses. Macroscopic and microscopic investigations of postoperative specimen
      allowed to set final diagnosis: stromal sarcoma with intermediate grade of
      malignancy, which showed an aggressive growth in the surrounding tissue and
      demonstrated moderate, focal polymorphism and different amounts of the mitoses in
      different areas.

PMID- 9553321
TI  - [Spontaneous tumor regression].
AB  - Spontaneous remission of cancer is a rare but definitely observed phenomenon.
      Spontaneous remission is defined by partial or total disappearance of a proven
      malignant tumor, without adequate medical treatment. It has been estimated that
      it occurs no more than once in 60,000 to 100,000. The cause of phenomenon is
      multifold: immunologic, hormonal and psychological mechanism as well as
      elimination of carcinogen (action of oncogenes, growth factors, cytokines) and
      apoptosis are postulated. In gynecological malignancies, excluding
      chorionepithelioma and breast cancer, spontaneous remission is rare.

PMID- 9553322
TI  - Current status of vitrification of embryos and oocytes in domestic animals:
      ethylene glycol as an emerging cryoprotectant of choice.
AB  - The cryopreservation of mammalian embryos has become an integral part of methods
      to control animal reproduction. Numerous vitrification solutions have been
      formulated with ethylene glycol in combination with macromolecules, sugars and
      other cryoprotective agents. These indicate that a study of ethylene glycol as a
      cryoprotectant of choice in vitrification studies would be promising. To
      understand the cryobiology of ethylene glycol, several factors have to be
      studied. These are: cryoprotectant toxicity, osmotic stress and temperature at
      exposure. Understanding these factors could lead to the formulation of
      vitrification protocols that would lead to higher viability rates after cooling.
      First, ethylene glycol must be used as the sole cryoprotectant in a solution
      without macromolecules and sugars. Second, partial dehydration and permeation
      prior to cooling to subzero temperatures must be studied to achieve accurate
      exposure and a one-step dilution method. Third, the toxic effects of ethylene
      glycol must be overcome without sacrificing its vitrification properties by
      combining step-wise exposure at appropriate temperatures, low concentration and
      decreased volume. Fourth, the long-term effects of ethylene glycol on exposed or
      vitrified embryos must be determined. Lastly, the influence of culture on the
      viability of vitrified embryos must be studied to improve viability rates after
      warming.

PMID- 9553323
TI  - In vitro viability of mouse zygotes vitrified in ethylene glycol.
AB  - A study was made to determine if mouse zygotes can be effectively vitrified in 7
      M ethylene glycol in modified Dulbecco's phosphate buffered saline (PB1) and to
      find out if the development of vitrified-warmed zygotes in vitro can be improved
      by renewing the culture medium. The results showed that without medium change,
      vitrification reduced the development of zygotes to the expanded blastocyst stage
      (p < 0.01). With medium change, the development rate of vitrified-warmed zygotes
      exposed in 7 M ethylene glycol for 1 or 2 min was similar to that of unvitrified
      zygotes. However, prolonged exposure (5 min) markedly reduced the development
      rates of vitrified-warmed zygotes to the expanded blastocyst stage (p < 0.05).
      When the zygotes were vitrified in 7 M ethylene glycol and diluted at 18 degrees
      C to 22 degrees C, a slower efflux of ethylene glycol from the cell might have
      occurred, leading to a toxic effect of ethylene glycol in culture. The
      development rates of vitrified embryos cultured with medium change at 24 hr did
      not significantly differ from the untreated control (89.0% vs 96.5%). In
      conclusion, this study showed that mouse zygotes can be vitrified in 7 M ethylene
      glycol in PB1 and that changing the culture medium can improve the in vitro
      development rates of vitrified-warmed zygotes to the expanded blastocyst stage.

PMID- 9553324
TI  - Ultrasonographic evaluation of portal vein hemodynamics in experimentally bile
      duct ligated dogs.
AB  - The purpose of this study was to evaluate the relationship between the results of
      laboratory examinations and ultrasonographic findings, especially portal vein
      hemodynamics in experimentally bile duct ligated dogs. Biliary obstruction was
      accomplished by surgically occluding the common bile duct in five dogs. All the
      dogs became visibly jaundiced within 24 hours after surgery. The total protein
      and albumin/globulin ratio showed a gradual decrease throughout the examination
      period, while blood urea nitrogen reached its peak in the 6th week and decreased
      to pre ligation values by the 10th week. Similar trends were noted in the
      alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and
      direct and total bilirubin. Total cholesterol and fasting serum bile acid levels
      rapidly increased after surgery to peak values between the 2nd and 4th week, and
      then gradually decreased, but still remained high throughout the experiment
      period. The portal flow volume and velocity significantly (p < 0.05) decreased
      while only a slight increase was noted in the congestion index after bile duct
      ligation. The cross sectional area of the portal vein changed insignificantly.
      Bile duct and gallbladder distention was evident within the 1st week after
      ligation but there was little change in the echogenicity of the liver parenchyma.
      The results of this study suggest that the determination of Doppler ultrasound
      parameters of hepatic hemodynamics, especially the portal vein flow indices, may
      contribute to a better noninvasive assessment of the canine patient with biliary
      obstructive disease.

PMID- 9553326
TI  - Functional enucleation of mouse metaphase II oocytes with etoposide.
AB  - Mouse metaphase II (M II) oocytes were exposed to 50 micrograms/microliters
      etoposide (ETO) before and after parthenogenetic activation with 7% ethanol and
      they were washed with 0.75 M sucrose. The ETO treated parthenogenetically
      activated oocytes were cultured or fused to single blastomeres of late 2-cell
      stage mouse embryo to test their ability to support development in vitro. In
      parallel untreated parthenogenetically activated oocytes were cultured to serve
      as control. None of ETO treated oocytes developed beyond the 2-cell stage,
      whereas 4% of the reconstituted embryos and 35% of control developed to
      blastocysts. It is concluded that mouse M II oocytes can be functionally
      enucleated by ETO treatment and can be used for nuclear transfer experiments.

PMID- 9553325
TI  - Potentially virulent Newcastle disease viruses are maintained in migratory
      waterfowl populations.
AB  - Forty-seven Newcastle disease virus (NDV) strains isolated from fecal samples of
      waterfowls in Alaska and Siberia from 1991 to 1996 were analyzed for their
      virulence. None of the viruses formed plaques on MDBK cells in the absence of
      trypsin. Of these, 29 strains showed virulent character by the mean death time
      with the minimum lethal dose in chicken embryos comparable to velogenic NDV
      strains. Of the 29 strains, 11 were sequenced for their fusion protein (F) gene.
      The results showed that 5 of them contained a pair of dibasic amino acids at the
      cleavage site of the F, which is of a virulent type. The present results suggest
      that potentially virulent strains of NDV are maintained in migratory waterfowl
      populations in nature, and that some of those may be transmitted to domestic
      poultry and acquire pathogenicity during passages in chicken population.

PMID- 9553327
TI  - [The effect of the formulation of a skin cream with a procyanidin polymer base
      and its effect on skin lesions caused by herpesviruses].
AB  - Procyanidin polymers are reported to be virostatic and virucidal in vitro. In
      this experiment we showed, on a hairless mouse model, biological effects of these
      agents, already demonstrated in vitro on cell cultures. Several dermic cream
      compositions have been tested and compared for reduction of HSV1 cutaneous
      lesions. In this study, it appeared clearly that active principle dosage form is
      as important as the biological effect of the agent. Composition and water content
      influence permeation speed, contact time with surface skin layers and
      consequently the pharmacological effect on herpetic skin injuries.

PMID- 9553328
TI  - Interpreting the standard of care.

PMID- 9553329
TI  - Clinical application of the new civil airman vision standards and certification
      procedures.
AB  - INTRODUCTION: The final rule revising the civil airman medical standards became
      effective September 16, 1996. The purpose of this study was to review changes in
      the vision standards and procedures and how they relate to the clinical
      optometrist. METHODS: Revision of Airman Medical Standards and Certification
      Procedures and Duration of Medical Certificates; Final Rule, (14 CFR, Parts 61
      and 67) and the Guide for Aviation Medical Examiners, published by the Federal
      Aviation Administration's Office of Aviation Medicine, were reviewed, and those
      parts pertaining to the clinical optometrist were summarized. DISCUSSION: The
      uncorrected distance visual acuity standards for first- and second-class airmen
      have been deleted. New equivalent near-vision standards were established for all
      classes of airmen. A major change--for pilots > or = 50 years of age--was the
      addition of an intermediate vision requirement of 20/40 or better at 32 inches
      for both first- and second-class medical certificate holders. Although the third
      class medical certificate is still valid for 24 months after the date of
      examination for those > or = 40 years of age, the certificate is now valid for 36
      months for those < 40 years of age. CONCLUSION: The new vision standards
      primarily affect the elderly pilot. Ophthalmic considerations in the application
      of the new vision standards are reviewed.

PMID- 9553330
TI  - Ocular cicatricial pemphigoid: case report.
AB  - BACKGROUND: The main characteristic of ocular cicatricial pemphigoid is
      subepithelial conjunctival fibrosis, which, if progressive, can lead to
      conjunctival shrinkage and symblepharon formation. Other characteristics include
      entropion, trichiasis, dry eye, cornea ulceration, neovascularization, and
      keratinization. Ultimately, blindness may occur. Cicatricial pemphigoid may also
      affect the skin and mucous membranes, including the nose, oral cavity, pharynx,
      esophagus, anus, and vagina. Treatment involves systemic immunosuppressants and
      corticosteroids to suppress active inflammation. CASE REPORT: A 69-year-old man
      had symblephara, conjunctival shortening, and extraocular manifestations, and was
      diagnosed with ocular cicatricial pemphigoid on the basis of clinical appearance
      and immunofluorescent studies. Treatment included oral Dapsone, prednisone, and
      azathioprine to stabilize the condition. CONCLUSION: Close monitoring of ocular
      cicatricial pemphigoid is imperative for ocular manifestations and for
      extraocular complications occurring with this progressive autoimmune disease and
      its treatment.

PMID- 9553331
TI  - Optometric manpower in the Commonwealth of Puerto Rico: estimates and
      projections, 1982-2025.
AB  - BACKGROUND: The 1982 study investigated the potential impact of the IAUPR School
      of Optometry on the adequacy of supply of optometrists in Puerto Rico for the
      years of 1980-2000. This article is designed to: (1) update the 1982 study; (2)
      appraise the accuracy of the 1982 projections; (3) re-evaluate the status of
      optometric manpower in Puerto Rico through the year 2025; and (4) provide the
      School of Optometry with information necessary to make informed judgments about
      future enrollments. METHODS: Estimates of supply are based on data from the
      Colegio de Optometras de Puerto Rico, the Seccion de Oftalmologia de la
      Asociacion Medica de Puerto Rico, and the enrollment and graduation registries
      from the School of Optometry. Requirements are based on estimates of annual
      effective demand, provider-to-population ratios, per capita demand, and
      optometric productivity. RESULTS: Optometrists comprised 52.2% of Puerto Rico's
      actively practicing vision care manpower in 1995, with a mean optometrist-to
      population ratio of 8.2 per 100,000. The number ranged from 28 in Mayaguez to 107
      in San Juan. Under different assumptions regarding supply, productivity, and
      demand, surpluses and deficits are estimated and projected for the years 1995 to
      2025. CONCLUSIONS: Depending on the assumptions used, an undersupply or an
      oversupply of optometrists may be found in Puerto Rico, currently and in the
      future. Projections of supply and demand predict a considerable range--from a
      surplus of 961 optometrists to a deficit of 2,085 optometrists in the year 2025.

PMID- 9553332
TI  - Keratocytes: no more the quiet cells.
AB  - BACKGROUND: In the past, the keratocytes of the adult cornea have been
      characterized as quiescent cells populating the stroma. Recent research and the
      introduction of laser refractive procedures have forced us to reassess this
      notion. METHODS: By reviewing recent, pertinent papers, an attempt was made to
      give an overview of the new information the scientific community is learning
      about keratocytes. This overview assesses the heightened interest in the
      keratocytes, while maintaining a clinical perspective. Where applicable, this
      information was tied in with our own laboratory observations. RESULTS: It is
      becoming increasingly clear that keratocytes may play a vital role in regulating
      the stromal constituents, while also providing structural stability in
      maintaining the interlamellar organization and, thus, promote corneal
      transparency. Keratocytes form a communicating network of cells linked in a
      anterior-posterior fashion, as well as laterally. This ability to communicate
      appears instrumental in triggering and orchestrating the corneal response in
      wound healing. External corneal injury, such as epithelial debridement and
      excimer laser exposure, can cause profound anterior keratocyte loss. These cells
      are replaced by aggressive stromal cells, which may play an important role in the
      formation of scar tissue and corneal haze. CONCLUSION: Keratocytes play an
      important role in both the healthy and the injured cornea. It appears that the
      improved outcomes of laser refractive procedures will--to a large extent--depend
      on our ability to maintain keratocyte health, while also controlling the negative
      effects of cells replacing injured or dead keratocytes.

PMID- 9553333
TI  - Optometry's first drug law: a personal memoir.

PMID- 9553334
TI  - [Analysis of cytological values of bronchoalveolar lavage in allergic
      inflammation of the bronchopulmonary system].

PMID- 9553335
TI  - [Problems of cytological diagnosis of some tumors of the anterior mediastinum].

PMID- 9553336
TI  - [Clinical value of total and free prostatic specific antigen in prostatic
      cancer].

PMID- 9553338
TI  - [Fluorescent microscopy in studies of microbiopsy specimens of the lung and
      bronchoalveolar lavage].

PMID- 9553337
TI  - [Epidermal growth factor receptors and their ligands as molecular markers of
      breast cancer prognosis and hormone sensitivity].

PMID- 9553339
TI  - [Spermoplasma protein markers in laboratory diagnosis of male sterility in
      diseases of male reproductive system].

PMID- 9553340
TI  - [Cytomegalovirus infection--modern diagnosis].

PMID- 9553341
TI  - [Modern aspects of automation in microbiology, epidemiology and chemotherapy].

PMID- 9553342
TI  - [On the diagnosis of Chlamydia infections].

PMID- 9553343
TI  - [PCR diagnosis of sexually transmitted diseases].

PMID- 9553344
TI  - [Agents of opportunistic infections--role in human infectious pathology and
      methods of laboratory diagnosis].

PMID- 9553346
TI  - [Polymerase chain reaction in diagnosis and treatment control of infectious
      diseases].

PMID- 9553345
TI  - [Laboratory assessment of tissue oxygen intake: blood gases and CO-oximetry
      (lecture)].

PMID- 9553347
TI  - [Experience gained in applying the expert approach to assessing the result of
      patient's analyses made in chemical plants laboratories].

PMID- 9553348
TI  - [Enzyme immunoassay in the laboratory diagnosis of human immunological
      disorders].

PMID- 9553349
TI  - [A variant of radioimmunoassay of alpha-fetoprotein].
AB  - A variant of liquid-phase radioimmunoassay (RIA) with murine monoclonal
      antibodies E7(B2-1) to human alpha-fetoprotein (AFP) is described. AFP levels
      were measured by RIA with a commercial DIAplus kit in the sera of patients with
      germinogenic tumors and of pregnant women.

PMID- 9553350
TI  - [Efficiency of a laboratory: opinions and evaluations of clinical physicians].
AB  - The opinions of 356 clinicists on the priority functions of a biochemical
      laboratory are analyzed and the efficiency of these functions performed by
      laboratories of a diagnostic center evaluated. The main laboratory functions were
      rated in accordance with the results of analysis. Besides the accuracy of the
      results, the respondents named time needed to obtain the results, the possibility
      of urgent information on the presence of manifest abnormalities, etc., as the
      most important factors. The author comes to a conclusion that other than
      analytical functions of laboratories are to be strictly defined and described as
      standards.

PMID- 9553351
TI  - [Antiphospholipid syndrome (Hughes syndrome): 10 years of study in Russia].

PMID- 9553352
TI  - [Arterial hypotension in the elderly].

PMID- 9553353
TI  - [Variability of heart rate in postmyocardial infarction patients: clinical
      implications, problems and prospects].

PMID- 9553354
TI  - [Pulmonary lesion in polymyositis and dermatomyositis].

PMID- 9553355
TI  - [Clinicofunctional and psychological characteristics of patients on
      rehabilitation and aortocoronary bypass].

PMID- 9553356
TI  - [Hepatolienal syndrome in patients with chronic lymphoid leukemia and liver
      cirrhosis: similarities and differences of macrophagal function].
AB  - Macrophagal function of the liver and spleen was studied using 99mTc dynamic
      scintigraphy in 31 patients with chronic lymphoid leukemia (CLL) and 11 patients
      with hepatic cirrhosis (HC). Total accumulation of the radionuclide in the above
      patients took place with more active participation of the spleen and less active-
      of the liver. Macrophagal function of the spleen and the liver was activated in
      CLL patients, whereas hepatic cirrhosis was accompanied by enhanced splenic
      function and diminished capacity of the liver for phagocytosis. Mechanisms of
      such phenomena are discussed.

PMID- 9553357
TI  - [Rheological and hydrodynamic properties of blood from patients with stable
      angina pectoris: correction with high molecular polyethylene oxide].
AB  - Rheological and hydrodynamic properties of blood taken from patients with stable
      angina pectoris were investigated in different periods (1, 7 and 28 days) of
      combined treatment (calcium antagonists, nitrates, beta-blockers, aspirin). The
      high viscosity syndrome (elevated blood viscosity, red cell aggregation,
      hyperfibrinogenemia) was registered before treatment, 1, 7 and 28 days after
      beginning of the treatment. Low hydrodynamic index (the speed of blood flow in
      turbulent regimen) reflected insufficiency of endogenic antiturbulent factor in
      the blood. The addition of high-molecular-weight polyethylene oxide to blood
      samples in concentration 2 x 10(-6) promoted normalization of the hydrodynamic
      index and decline of red cell hyperaggregation.

PMID- 9553358
TI  - [Antigliadin antibodies in the absence of celiac disease].
AB  - Antigliadin antibodies (AGA) mark celiac disease, but AGA are also encountered in
      IgA-nephritis, psoriasis, sickle-cell anemia, hepatic disorders, juvenile
      rheumatoid arthritis, autoimmune thyroidism and in persons who occupationally
      contact great amounts of wheat. AGA IgA and/or IgG were registered in 19 of 60
      subjects (51 adults and 9 children) with various immunomediated diseases without
      symptoms of celiac disease: in 4 cases of chronic active hepatitis, in 2 of 4
      cases of chronic persistent hepatitis, in 4 of 16 cases of rheumatoid arthritis,
      in 3 of 19 cases of IgA-deficiency, in 1 of 8 cases of SLE, in 2 cases of
      postvaccine reaction, in all the single cases of juvenile rheumatoid arthritis,
      focal scleroderma, macroglobulinemia. IgA only occurred in in 6 patients, IgG- in
      6 patients, both IgA and IgG in 7 patients. The most pronounced positive reaction
      to AGA was recorded in 8-year-old girl with juvenile rheumatoid arthritis. The
      emergence of AGA in immunomediated diseases may be attributed to the response to
      food protein in pathological conditions and is often unrelated closely with
      celiac disease.

PMID- 9553359
TI  - [Hemocarboperfusion in combined treatment of leptospirosis].

PMID- 9553360
TI  - [Platelet hemostatic changes in patients with chronic alcoholism stage II in rest
      and exercise].
AB  - Platelet hemostasis was studied in 23 patients with chronic alcoholism (CA) stage
      II at rest and under muscular exercise. At rest, the patients had elevated
      spontaneous aggregation of platelets and more active start of adrenaline and
      ristomycin aggregation. Exercise stimulated spontaneous platelet aggregation,
      enhances adrenaline and ristomycin aggregation. According to adrenalin test 32%
      of the examinees had platelet dysfunction. According to ristomycin aggregation,
      vascular endothelium was impaired in 95.7%of the patients. Thus, it is evident
      that CA stage II patients develop disorder of platelet hemostasis and vascular
      endothelium. Such patients are at high risk of thrombogenesis.

PMID- 9553361
TI  - [Urinary excretion of glycosaminoglycans in patients with chronic pyelonephritis
      and chronic glomerulonephritis].
AB  - Glycosaminoglycanes (GAG) were measured in 24-h urine of patients with chronic
      pyelonephritis (CP) and chronic glomerulonephritis (CGN) at different stages of
      nephrosclerosis. These patients developed hyperglycosaminoglycanuria at early
      stages of nephrosclerosis before establishment of chronic renal failure. There is
      a positive correlation between the severity of excretion of GAG and leukocyturia
      in CP patients (p < 0.05). Estimation of GAG 24-h urinary excretion can help
      evaluate metabolism of connective tissue of the kidneys in CP and CGN patients
      for early diagnosis of nephrosclerosis, control of the treatment efficacy and the
      disease prognosis. It can also serve as additional criterion for rating of
      inflammation. The method is non-invasive, informative, available for clinical
      diagnostic laboratories.

PMID- 9553362
TI  - [Ecological zones of Dagestan territory and epidemiology od acute leukemia in
      older age groups].
AB  - The authors report annual acute leukemia incidence through 1980 to 1995 in
      Dagestan in respect of implications of of environmental factors. The highest
      leukemia incidence rate was in the age group over 50 years. Acute leukemia
      incidence varied with years, sex and territory zones. Active utilization of
      chemical fertilizers in agriculture proved a contributing factor in the onset of
      acute leukemia, especially in persons older than 50 years.

PMID- 9553363
TI  - [Long-term subfebrility].

PMID- 9553364
TI  - [A case of allergic eosinophilic granulomatous angiitis (Churg-Strauss
      syndrome)].

PMID- 9553365
TI  - [Syndrome of functional dyspepsia: disputable and unsolved problems].

PMID- 9553366
TI  - [History of teaching clinical medicine: leiden advance].

PMID- 9553367
TI  - [Current objectives for the improvement of work conditions and prevention of
      occupational diseases among miners].
AB  - Workers engaged into deep mining are subjected to occupational factors intensity
      of which is significantly higher than the allowable. Changing the mining
      enterprises involves deterioration of the working environment, increase in
      occupational morbidity. Features of the working environment, parameters of main
      occupational entities, recent social instability at mining enterprises
      necessitate further investigations on the problem.

PMID- 9553368
TI  - [Medical and social problems related to cardiovascular diseases among the miners
      of the Donbass coal mines].
AB  - Occurrence and course of cardiovascular diseases in miners of Donbass is due to
      social and occupational factors that should be considered in early diagnosis and
      prophylaxis. Sudden coronary death of miners at the workplace or after leaving
      the mine is associated with triggering of occupational factors and now is legally
      appreciated as an occupational accident.

PMID- 9553369
TI  - [The influence of dust and heating microclimate on lipid peroxidation].
AB  - In experimental pneumoconiosis both under normal and heating ambient temperature
      lipid peroxidation is not activated, although heating microclimate increases
      alteration of lung tissue and induces rapid and intensive pulmonary fibrosis.
      Association of dust and heating microclimate prolongs a period of "stress"
      myocardial affliction due to intensified lipid peroxidation and exhausted
      endogenous glutathione peroxidase, afterwards lipid peroxidation decreases with
      progressing sclerosis and fat degeneration in heart.

PMID- 9553370
TI  - [Irregular heart rate correction among miners with early signs of pulmonary
      diseases by the method of alternative biocontrol of the heart contraction
      frequency].
AB  - The study covered 45 miners having anthracosilicosis and dust bronchitis. The
      registered signs were lower spectral intensity of high-frequency waves
      (oscillations period 3 to 36 s) and higher spectral intensity of low-frequency
      waves (oscillations period 36 s), asymmetry of blood pressure, higher systolic
      and diastolic BP before stress period of adaptation. Adequate therapy associated
      with biologic regulation of cardiac rhythm restores normal regulation.

PMID- 9553371
TI  - [Morbidity with temporary disability among miners of underground and surface
      mines].
AB  - The authors studied morbidity with transitory disablement among miners of open
      and deep mines. The morbidity parameters appeared to differ reliably between deep
      miners and open-cut miners. The morbidity structure is demonstrated. The authors
      revealed strong direct correlation between the morbidity parameters and intensity
      of occupational hazards in the mine.

PMID- 9553372
TI  - [The impact of trinitrotoluene on eyes in miners].
AB  - Trinitrotoluene (TNT) effect on the eyes of 250 miners was studied. The length of
      service of the investigated group varied from one to twenty years. The specific
      trinitrotoluene cataract of various stages was observed in 54.7% of the
      examinees. The authors assume that the lens changes depend on the length of
      service and on the TNT concentrations in the body after predominant skin
      penetration.

PMID- 9553373
TI  - [Data on occupational diseases among health personnel and workers of medicine
      related industry in St. Petersburg].
AB  - A total of 105 occupational morbidity cases in health service workers were
      analyzed among 2914 occupational morbidity cases in St. Petersburg. Most of those
      cases among health service workers were drug allergies, tuberculosis was
      relatively rare. The study revealed low efficiency of periodic medical
      examinations conducted for early diagnosis of occupational diseases. Alarming
      evidence is rare diagnosis such occupational diseases as hands overstrain,
      strained working posture, disorders due to physical factors, viral B hepatitis.

PMID- 9553374
TI  - [Occupational environment and health status among workers at the enterprises of
      "Sibtechspetsmontazh++" trust].

PMID- 9553375
TI  - [Common shortcomings and mistakes in monographs and textbooks on industrial
      ecology].

PMID- 9553377
TI  - Births, marriages, divorces, and deaths for July 1997.

PMID- 9553378
TI  - [How should the tuberculosis control activities of health center be?].

PMID- 9553379
TI  - [Factors affecting active-life orientation among the elderly in a community in
      Japan and its relationship to social activities].
AB  - We surveyed a stratified random sample of 205 person from 45,500 residents, aged
      65 years or older, in a city of Japan using an interview schedule including
      scales of active-life orientation, social activities and other covariates. A
      total of 157 (77%) participated in the study. The main results were as follows:
      1) Significantly higher scores of active-life orientation were observed in those
      who currently worked, than in those who did not work in males and females (p <
      0.05). In males, scores of active-life orientation were significantly higher in
      those who had hobbies than in those who did not (p < 0.05); in those who traveled
      during the past year than in those who did not (p < 0.05). 2) In multiple linear
      regression analysis, PGC scale scores positively and significantly correlated
      with score of active orientation in males and females (p < 0.05). Age negatively
      correlated with the scores in males. Scores of affiliation orientation positively
      correlated with scores of active orientation, and satisfaction with available
      social support negatively correlated with the scores in females (p < 0.05).

PMID- 9553381
TI  - [The evolution of the thought of "Yojo" and its function as a theoretical bases
      for development of health culture].
AB  - The purpose of this monograph is to clarify the role of "Yojo" on public health
      in Japan. Yojo is a traditional concept which has been used for the nourishment
      of life in Eastern cultures. These thoughts on Yojo were published under the
      title of Yojoron in ancient China. Yojoron was imported into Japan somewhere from
      the 7th to 10th centuries. In ancient and medievel Japan, there were few writings
      about Yojoron. However during the Edo period, Yojoron suddenly flourished.
      Dominant in Yojoron was diet. Issues such as exercise, mental control, and sexual
      restraint were also considered in the Bunka, Bunsei, and Tenpo periods (the first
      half of 19th century). Yojoron included not only matters of physical and mental
      health but various other matters regarding the general quality of life such as
      morality, domestic economy, culture and education. However other health-related
      issues such as longevity and absence of diseases, showed a simultaneous decrease
      in the importance. Also principles of Yojoron such as restraint and austerity in
      behaviour were liberalized. These trends indicated the basic shift in Yojoron
      from personal health care to self-culture for the entire quality of life.
      Writings on Yojoron were still published after the Meiji restoration (1868). The
      principle of Yojoron in the Meiji period was based on both social Darwinism and
      social revolution theories. The primary concerns of Yojoron were consolidated
      into achieving health and longevity by personal effort. Therefore Yojoron can be
      seen as the theory of lifestyle and quality of life in traditional societies in
      Japan. The public saw in Yojoron a design for living through improved health.
      This meant the Yojoron was a very refined art of living, and therefore, implies
      that health care should be integrated with entire self-development. The principle
      of Yojo offers the ideal foundation of 'health culture' in modern societies.

PMID- 9553380
TI  - [Effectiveness of a health education class to increase fish intake evaluated by
      serum fatty acid compositions].
AB  - For prevention of cardiovascular disease, we recommended increased fish intake
      for 50 middle-aged women and men of 40-83 years old at a three-month community
      based health education program in an inland farming community. The effectiveness
      of the education program was evaluated by examining changes in serum lipids and
      serum fatty acid compositions. For comparison, we selected 48 men and women of 38
      82 years old did not participated in the program. Before education, there was no
      significant difference in the dietary frequency of fish, meat, egg and dishes
      prepared with oil, mean values of serum lipids or serum fatty acid compositions
      except for saturated fatty acid, gamma-linolenic acid, dihomo-gamma-linolenic
      acid and alpha-linolenic acid. After three months, the frequency of fish intake
      of one or more times per day increased from 33% to 43% in the education group
      while the frequency of fish intake did not change in the control group. In the
      education group, serum n3 polyunsaturated fatty acid composition increased from
      8.8% to 10.6%. This fatty acid increase was primarily observed in
      eicosapentaenoic acid and docosahexaenoic acid. The n3/n6 ratio increased from
      0.21 to 0.31. In the control group, no change was observed in n3 polyunsaturated
      fatty acids. This study suggests that the community-based dietary education
      increased fish intake and serum n3 polyunsaturated fatty acids in women and men
      of 40 years old or older.

PMID- 9553382
TI  - [Relationship between subjective cognition and observed life-style in nursing
      students].
AB  - Complex interactions between long-standing lifestyles and genetic factors are
      strongly involved in the pathologenesis of adult diseases or chronic degenerative
      diseases. We usually use a questionnaire to obtain life-style information from
      subjects in a health survey. However, the response to questionnaires is a
      subjective recognition, therefore, it does not always precisely correspond to the
      actual situation. The purpose of this research is to compare the response to the
      questionnaire about life-styles with facts that can be objectively observed.
      Furthermore, each aspect of life-styles was examined on a mutual influence grade.
      The subjects were ninety-eight nursing college students aged from 18 to 23 years
      old, in good health. Subjective symptoms and daily life practices were
      investigated by a 15-item questionnaire, as the first step. Therefore, we asked
      them to record their behavior on a time chart, everyday for ten days. Seven days
      of serial records were obtained from sixty-four subjects (65.3% of 98 persons).
      1) The response "yes" to the questionnaire "Do you sleep well?" and "Do you fall
      asleep, easily?" was influenced by the hours of sleep, rather than what time the
      subjects "go-to-bed" or "get-up". The response to "Do you wake up often during
      the night?" expressed an actual situation, well. 2) For subjective cognition
      regarding excretion, the answer for "constipation" was associated with the number
      of defecation per week, though the answer for "diarrhea" was not. 3) The answer
      to "Do you eat breakfast?" reflected the actual situation. However, the answer
      for "Do you eat between meals?" did not express the actual situation, that is,
      even the subjects who answered "occasionally" or "I don't eat between meals" had
      eaten between meals 6.1 times per week, on average. 4) There were mutual
      influences among sleeping, eating breakfast and excretion.

PMID- 9553383
TI  - [Trend of aging on the number of teeth investigated through a survey of dental
      health representation in a simple equation by using a kinetic method and its
      application].
AB  - A survey of dental health was conducted on 6,933 residents (aged 61.8 +/- 11.1)
      in 4 villages Nara Prefectural Uchiyoshino Health Center administers. Examinees
      were divided into 7 ages groups. The mean value of present teeth at each age
      group was calculated. Age dependency of number of teeth was investigated with a
      kinetic model based on the following premise. 1. Changes between age groups can
      be treated as a time series occurrence. 2. Number of missing teeth can be
      estimated as 29 - that of present teeth. Results show that the rate of decrease
      of the number of present teeth is of a first order in itself and the number of
      missing teeth. It can be mathematically expressed as follows: -dX/dt = k.X.(29 -
      X).......eq. (1). in which X = number of present teeth, 29 - x = number of
      missing teeth k = rate constant, t = time. From this simple relationship the
      following are suggested 1. Tooth loss is caused by the interaction of present
      teeth and sites where teeth are lost. 2. Integration of eq. (1) yields ln?(29 -
      X)/X? = 29.k.t + a.......eq. (2). in which 0 < X < 29, t = time from the youngest
      age group (20-29), a = constant. It appears that, from eq. (2), the dental health
      of a community is determined by two coefficients, 29.k and a. 3. Helping a person
      realize his present and future dental state and to motivate action for prevention
      of tooth loss by showing him his rate of decrease, "tooth age" and the predicted
      number of teeth a certain years later calculated from eq. (1) and eq. (2), can be
      of great value. 4. Eq. (2) is transformed to X = 29/?exp(29.k.t + a) + 1?, which
      represents the reverse S-shaped curve of the age dependency of the number of
      teeth. 5. Applying this method to cohort analysis will enable forecast of the
      trend of the number of teeth.

PMID- 9553384
TI  - [A study of the association between the aortic pulse wave velocity and
      atherosclerotic risk factors among Japanese Americans in Seattle, U.S.A].
AB  - Cardiovascular disease prevention screening was conducted among 1389 Japanese
      Americans in Seattle, Washington, U.S.A. from 1989 to 1994. The association
      between atherosclerotic risk factors and the aortic pulse wave velocity (PWV), an
      indicator of atherosclerosis, was examined by using multiple logistic regression
      method. Based on a study in 1996 by Suzuki et al. on the association between PWV
      and atherosclerotic indicators, abnormally high PWV was defined as 8.0 m/sec. and
      over for those less than 60 years of age and 9.0 m/sec. and over for those 60
      years of age and older Significant odds ratios to estimate the risk for the
      presence of abnormally high PWV were found in age >or= 60 years (4.31, p <
      0.001), hypertension (2.00, p < 0.001), diabetes (5.65, p < 0.001), current
      drinker (0.44, p < 0.001), ex-drinker (0.49, p < 0.05), and ex-smoker (1.82, p <
      0.01) among men. Women showed a similar association: age > or = 60 years (3.03, p
      < 0.001), hypertension (1.94, p < 0.01), diabetes (2.47, p < 0.05), TC/HDL-C >or=
      4.5 (1.98, p < 0.001), current drinker (0.47, p < 0.001), and ex-drinker (0.45, p
      < 0.05). Our findings are almost identical to those from other studies showing
      the association between coronary heart disease and its risk factors. The question
      of whether PWV can be a predictor of atherosclerotic diseases, particularly
      coronary heart disease, remains to be answered by additional studies. However,
      PWV may serve as a simple and valuable indicator to estimate the extent and
      severity of asymptomatic atherosclerosis in the large artery.

PMID- 9553385
TI  - [Changes in knowledge of HIV/AIDS and attitudes for PWA in Tokyo: 1992-1995].
AB  - In order to assess changes in knowledge of HIV/AIDS and attitude for People With
      HIV/AIDS (PWA), interview surveys (Dec. 1992, Jan. 1994, Jan. 1995) were carried
      out annually on random samples of the general public in Tokyo, age between 15-69
      years. In total, 4,270 individuals were sampled, with an average response rate of
      63.2%. Answers were scored and classified in 12 sex and age sub-groups.
      Additionally, correlations between scores of questions and social indices were
      analyzed. The results of the study are as follows: 1) The 15-19, 20-29 and 30-39
      age groups showed higher scores on knowledge about HIV transmission modes. During
      the entire study period, the score increased in 7 groups, but decreased in 5
      groups. 2) The 30-39 and 40-49 age groups showed higher scores on knowledge about
      HIV antibody test. During the period, the score increased in 11 groups, and among
      them 6 groups showed statistically significant (p < 0.05) increases. However, the
      score decreased in 9 groups at the third survey. 3) The 15-19, 20-29 and 30-39
      age groups showed higher scores on acceptable attitudes for PWA. During the
      period, the score increased in all groups, and among them 3 groups showed
      statistically significant (p < 0.05) increases. 4) Rank correlations between two
      scores-knowledge quantity about the transmission modes and acceptable attitudes
      for PWA-were positive (0.2 < R) and statistically significant (p < 0.05) in 11
      groups at the first survey, 9 groups at the second, and 6 groups at the third. 5)
      During the entire study period, 6 groups showed positive correlations (0.7 < R)
      between two changes: (1) score of knowledge about the transmission modes and (2)
      score of acceptable attitudes. 6) During the entire study period, 10 groups
      showed positive correlations (0.7 < R) between two changes: (1) score of
      acceptable attitudes and (2) number of newspaper articles regarding acceptance or
      discrimination of the PWA. 7) Knowledge about HIV/AIDS in the general public in
      Tokyo showed increase in younger generation, but there is concern of decrease in
      the older generation. These result indicate that acceptable attitude forward PWA
      are affected by related knowledge about the transmission modes and mass-media
      information, and must be considered in HIV/AIDS programs.

PMID- 9553386
TI  - [Follow up study of community-based group education for body weight reduction].

PMID- 9553387
TI  - [A support system after the health examination for the aged].

PMID- 9553388
TI  - [An analysis of factors associated with the increase of in-patient medical
      expenditures for the elderly in Fukuoka Prefecture].
AB  - In order to evaluate factors associated with the increase in the in-patient
      medical expenditures for the elderly in Fukuoka prefecture during the period from
      1987 to 1991, an analysis was conducted based on the data of 10 Health Care
      Regions. According to the results, there were two patterns in the increase. The
      first was the pattern observed in the southern part of the prefecture, where most
      of the increase in the in-patient medical expenditures for the elderly was
      explained by the increase of medical expenditures per capita. Furthermore, this
      increase per capita was due to the increase in utilization rate. This pattern is
      considered to be associated with the increase of general hospital beds as well as
      with the increase of the dependent elderly in the regions. The second pattern was
      observed in urban regions, such as Fukuoka and Kitakyushu, where the increase of
      in-patient medical expenditures for the elderly was mainly due to the increase in
      the number of elderly in the regions. This pattern is considered to be associated
      with the increase in the population categorized as the aged household. The
      present result suggests that in order to control the medical expenditures for the
      elderly, different service-mix strategies will be necessary, respecting the socio
      economic characteristics of each region.

PMID- 9553389
TI  - [A comparative study of local mental health and welfare policies in Japan: Cases
      of Tokyo Metropolitan Government and Yamaguchi Prefecture].
AB  - In this article the mental health and welfare policies of the Tokyo Metropolitan
      Government and Yamaguchi Prefecture were analyzed, and the features of their
      development and problems were discussed. The results are as follows: a) The
      emphasis of the mental health and welfare policies both of Tokyo and Yamaguchi
      experienced changes according to national policies and is to be divided into the
      following four periods and key concepts. The 1st period (1950-1964): no policy or
      increase of psychiatric beds The 2nd period (1965-1975): dawn of "from hospital
      to community" The 3rd period (1976-1987): workplace for the mentally ill The 4th
      period (1988-present): accommodation for the mentally ill b) During the 2nd
      period, in terms of increase in psychiatric beds, the Tokyo Metropolitan
      Government tried to limit increase, whereas Yamaguchi Prefecture accommodated it.
      c) In the field of community mental health, the most remarkable development in
      Tokyo in recent years is that the number of workshops and group homes grew
      dramatically. The original policy of the Tokyo Metropolitan Government to
      subsidize such small institutions was recommended in the report of Local Advisory
      Council on Mental Health and Welfare (Chiho-Seishinhokenhukushi-shingikai). As a
      result many voluntary groups operate those institutions with help of subsidy. On
      the contrary the development in Yamaguchi is slow, because the establishment of
      institutions for rehabilitation was mainly implemented by the regulation of
      national law which demands high costs for its building and land. d) The original
      policies of the Tokyo Metropolitan Government, however, is based on the premise
      that a shortage exists of institutions for rehabilitation regulated by Mental
      Health and Law. In this situation, therefore, the development of community mental
      health depends on a subsidy from local government, development of community
      mental health depends on a subsidy from local government, development of
      voluntary groups, and accessibility to social services.

PMID- 9553390
TI  - [Exposure to tobacco smoke in a Japanese urban population. An analysis using
      biochemical markers of smoking].
AB  - An epidemiological study in an urban population was conducted to investigate
      exposure to tobacco smoke using two biochemical markers of smoking. In 1993 and
      1994, expired air carbon monoxide (EACO) concentrations were determined with a
      small portable CO monitor for 4,619 subjects aged 30 and over, who had been
      randomly selected from residents of S-city in Osaka Pref, and who had received a
      health examination for cardiovascular disease at the National Cardiovascular
      Center. Urinary cotinine (UCOT) concentrations were determined using gas
      chromatography for 480 subjects, who were nonsmokers, and who had received a
      health examination during Sep. and Nov. in 1994. They also completed a
      questionnaire about smoking habits and potential of passive smoking. In this
      study smoking prevalences were 45% in men and 11% in women according to the
      questionnaire. Among nonsmokers 55% of men and 46% of women reported some degree
      of exposure to tobacco smoke. The EACO levels were related to the number of
      cigarettes smoked per day in a dose-response fashion. The time elapsed since last
      smoked and the usual depth of inhalation, in addition to the number of
      cigarettes, had effects to EACO level. The optimal EACO cut-off points selected
      to differentiate smokers and nonsmokers were between 6 and 7 ppm for men, and 5
      and 6 ppm for women with a sensitivity and a specificity of about 90%. The hours
      spent with tobacco smoke at home, whether there was a smoking spouse or not, and
      the time elapsed since last inhalation of smoke affected EACO level in
      nonsmokers. The frequency of going to an amusement place, a bar or a restaurant,
      and the hours spent with tobacco smoke in a work place had effects on UCOT level
      in non-smokers. The proper use of biochemical markers for tobacco smoke may be of
      value in developing more effective strategies for smoking problems control.

PMID- 9553391
TI  - [The relationship between smoking behavior and self-esteem among elementary and
      junior high school students].
AB  - OBJECT: This study examined the relationship between smoking behavior and self
      esteem among Japanese early adolescents. METHOD: The study sample comprised 1,486
      fourth through ninth grade students from 10 elementary schools and six junior
      high schools throughout nine prefectures. Data were collected using an anonymous
      self-administered questionnaire which included items measuring smoking behavior,
      self-esteem, intention to smoke in the future, self-efficacy to refuse peer
      pressure to smoke, the smoking behaviors of their parents, siblings and friends.
      Self-esteem was measured using the Harter Perceived Competence Scale which
      includes four areas: cognitive, social, physical, and general. RESULTS: The main
      results were as follows: 1) Ever smokers had lower cognitive and general
      competence scores, but a higher physical competence score than never smokers,
      especially among males. 2) Ever smokers had more smoking parents, siblings and
      friends than never smokers. 3) Ever smokers had stronger intention to smoke in
      the future than never smokers. 4) Ever smokers had lower self-efficacy to refuse
      peer pressure to smoke than never smokers. CONCLUSION: The results of this study
      about the relationship between smoking behavior and self-esteem were consistent
      with those of some previous studies in the U.S. Therefore, it is suggested that
      effective smoking prevention programs for Japanese early adolescents should
      include strategies to enhance self-esteem.

PMID- 9553392
TI  - [Effects of pregnancy and lifestyles including food intake on bone density of
      pregnant women].
AB  - Bone densities measured by ultrasound at the calcaneus, and urinary
      hydroxyproline (H.P) and calcium (Ca) concentrations adjusted for creatinine
      (Cre) were measured in 79 pregnant women, aged 20 to 38 years, at 5-40 weeks of
      gestation. Stiffness calculated from the combined value of speed of sound and
      broadband ultrasound attenuation was used as an index of bone density. The
      relationships between Stiffness and period of gestation, urinary H.P/Cre and
      Ca/Cre, and such lifestyles as current and past food intake frequency, physical
      activity and history of participating in sports obtained by questionnaire were
      examined using stepwise multiple regression analysis, including age and weight as
      independent variables. 1) The means of Stiffness in women with the gestation
      period of more than 20 weeks (primipara 79.6, multipara 83.4) are a little lower
      than those of non-pregnant and healthy women within the same age range. 2) Period
      of gestation showed a significant negative correlation to Stiffness. Significant
      positive correlations were found between urinary H.P/Cre and period of gestation.
      These results suggest that bone resorption increases with stage of gestation and
      causes bone loss in pregnant women. 3) Significant relationships with Stiffness
      was found only in frequency of cow's milk intake before pregnancy among various
      lifestyle factors. Stiffness of the subjects who took cow's milk every day before
      pregnancy was significantly higher than those who took less than 2-3 times per
      week or none. This result indicates that cow's milk and dairy products intake
      before pregnancy may be important for bone mineral maintenance during pregnancy.

PMID- 9553393
TI  - [Factors influencing admission to nursing homes among frail and bedridden elderly
      persons receiving public health and welfare services].
AB  - A prospective study was conducted to elucidate the factors influencing admission
      to nursing homes among frail and bedridden elderly persons. The subjects were 149
      persons, 70 years of age and above, who were living in Goshiki-cho, Hyogo
      prefecture and were receiving services from public health and welfare
      organizations. All of the subjects had a family physician and their own residence
      or own room at home. A follow-up study of admissions to nursing homes was
      performed from 1991 to 1996. The main results were as follows: 1. During the
      study (about 5 years), 42.9% (N = 64) of subjects were staying at home, 38.9% (N
      = 58) died at home, and 16.8% (N = 25) were admitted to nursing homes. 2. To find
      factors influencing admission to nursing homes, an analysis using Cox
      proportional, hazard model was conducted. Major factors found were high age,
      women, disabilities of hearing and eyesight, and difficulty in communication. The
      admission rate to nursing homes was especially high among patients 90 years of
      age or greater. 3. The admission rate to nursing homes was higher in subjects
      receiving home help services compared to the rest of the group. 4. Remarkable
      differences in household composition were observed between those who continued to
      stay at home and those admitted to nursing homes. Among the subjects living alone
      or living with a spouse, the mean age was significantly higher in the group who
      were admitted to nursing homes than those staying at home. In the case of two or
      three-generation households, the admission rate to nursing homes was high when
      the household lacked caregivers.

PMID- 9553394
TI  - [State of bullying in a geriatric hospital].
AB  - Recently, reports of bullying and beatings among school children has brought
      these problems to the public attention. Unfortunately similar problems exist
      among the aged and institutionalized patients in geriatric hospitals, e.g.,
      covert teasing and bullying of the weak. Therefore, the present status of
      bullying or being bullied in our geriatric hospital was analyzed and their
      backgrounds studied to develop clinical countermeasures against bullying. Results
      of this study were as follows; 1. Nineteen percent of patients were victims of
      bullying, and patients who had performed the bullying were 3.0%. 2. Of those who
      were bullied 20.0% wanted to change hospitals, while 60.0% felt they could
      tolerate the situation or suppress their anger, and 13.3% of the patients who had
      exhausted their patience took revenge on the bully. 3. Patients who had been
      bullied tended to be more tenacious and had a high level of depression by Self
      rating Depression Scale (SDS). The apparent error rate in these results was
      22.5%.

PMID- 9553395
TI  - [An experience of smoking cessation supports for officials of a village as a
      beginning of tobacco control activities in the village].

PMID- 9553397
TI  - [A research on the present and the future of managial attitude toward
      contingencies in the assisted living residency for the elderly].

PMID- 9553396
TI  - [Preventive measures against hepatitis B virus infection in nursing schools in
      Japan].
AB  - To clarify the use of preventive measures against Hepatitis B Virus infection
      among nursing students, questionnaires were mailed to 488 nursing schools
      throughout Japan (including colleges and junior colleges). Two hundred and sixty
      eight nursing schools answered our questionnaire. The results are summarized as
      follows: 1. Eighty percent of the nursing schools that responded, regularly
      perform the HBs antigen test, and 70% conduct the HBs antibody test. However,
      only 29% carry out HB vaccinations. 2. Of the 172 schools (71%) that do not
      actually perform HB vaccinations, only 4% have a HB vaccination plan for the
      future. 3. The main reasons why the schools do not carry out HB vaccinations are:
      1) high cost (48%), 2) low risk of HBV infection among students (34%), 3) the
      students are thought to be themselves capable of preventing HBV infection (31%).
      4. Eighty percent of the nursing schools conduct an orientation program for their
      nursing students on how to prevent infection before their practical training at
      school as well as during their practical training at the hospital. 5. Thirty-five
      percent of the nursing schools have their own "Prevention of HBV Infection
      Manual", while some of the others use a manual provided by their training
      hospital. 6. In answer to the question "Do the instructors ask the students to
      report any potential risk of infection they encounter during their training in
      the hospital?", 88 approximately 89% of the schools said that they instruct their
      students to report all injuries involving a needle stick. Other questions
      relative to various circumstances were also asked. To the question of whether the
      school requires the students to report any wounds to their fingers or hands, the
      rate of "yes" answers was only 33%, although this information is essential to
      prevent avoidable risk. Conclusion In our investigation we found that the HBs
      antigen and the HBs antibody tests are both performed in a high proportion in
      nursing schools. Orientation concerning students' training at the hospital to
      prevent infection is also provided at a high rate. On the other hand, HB
      vaccinations are not widely performed. Manuals on the prevention of HBV infection
      are not used at a high proportion either. Also, the reporting system for students
      encountering any potential risks of infection is insufficient. We think that a
      more active prevention system for HBV infection should be organized in every
      nursing school.

PMID- 9553398
TI  - [Relationship between obesity level and subjective symptoms in junior high school
      students. Comparison between method of standard body weight and body mass index].

PMID- 9553399
TI  - [Endothelin and arterial hypertension].
AB  - Endothelins (ETs) are peptides of 21 amino acids synthesized and released by
      variety of cells. Endothelin (now this peptide is called endothelin-1 (ET-1)) was
      isolated and identified in 1988 by Yanagisawa et al. Following studies revealed
      two other isoforms of endothelin': Endothelin-2 (ET-2) and endothelin-3 (ET-3).
      All of them bind to two types of receptors (A and B (ET-A r, ET-Br). ET-A r are
      responsible for concentration mediating. Two subtypes of ET-B r are known. ET-B1
      r mediates vasorelaxation; ET-B2 vasoconstriction. ETs (especially ET-1) have
      variety of biological actions but the most important are vasoconstrictor and
      mitogenic action. Through these two mechanism ETs may participate in the
      pathogenesis and/or in the maintenance of hypertension in both experimental
      animal models and human essential hypertension. The intravenous infusion of
      synthetic ET induces a long-lasting elevation of blood pressure in experimental
      animals and in healthy humans. Number of studies have shown enhanced responses to
      ET in hypertensive subjects but decreased responses have also been reported.
      Similarly, plasma levels of ET-1 are either normal or elevated in experimental
      and human essential hypertension. Numerous investigators have suggested an
      interaction between ET and angiotensin-converting enzyme inhibitors through the
      renin-angiotensin system or through the accumulation of endogenous bradykinin.
      Also calcium antagonists of different classes prevent endothelin-induced
      contractions. Endothelin- converting enzyme inhibitor (phosphoramidon) and ET-A/B
      r antagonists (bosentan, BQ-123, FR139317) may have potential role as
      vasodilators in the treatment of hypertension.

PMID- 9553400
TI  - [Magnetic resonance arteriography as a method for diagnosing arteriosclerosis of
      the lower extremities].
AB  - The purpose of our study was the evaluation of usefulness of Magnetic Resonance
      Angiography in diagnostic process in patients with arteriosclerosis of lower
      extremities and complications such as aneurysms and pseudoaneurysms. 105 patients
      were examined using 2D TOF method. We concluded the results were very similar as
      in radiological examinations. The MRA is a very helpful method in evaluation of
      constriction and occlusion of iliac and femoral arteries and aorta.

PMID- 9553401
TI  - [Examination of veins with magnetic resonance imaging and it's place in the
      diagnostic algorithm of patients with deep venous thrombophlebitis].
AB  - The aim of our study was to show the results of the Magnetic Resonance
      Angiography of pelvis and lower extremities. 21 patients with clinical signs of
      venous thrombosis were examined. The obtained results show the MRA is very useful
      in evaluation of venous flow.

PMID- 9553402
TI  - [The influence of vitamin C and e or beta-carotene on peroxidative processes in
      persons with myocardial ischemia].
AB  - An increasing body of evidence suggests that beside hypercholesterolemia
      peroxidative processes and natural antioxidant defence system play important role
      in the development of atherosclerosis. Our earlier investigation showed the
      increased intensity of the peroxidative processes in the course of the acute
      myocardial infarction and unsatisfactory tocopherol, ascorbic acid and retinol
      status. The purpose of the present study was the evaluation of the effect of
      antioxidant vitamins supplementation by the period of 21 days on the peroxidative
      processes in patients after heart attack or after "bypass" admitted to the
      cardiological rehabilitation centre. Daily oral supplementation with vitamin C, E
      and beta-carotene decreased significantly plasma lipid peroxide concentration
      (TBARS). The highest drop in TBARS activity was found in the group after bypass.
      No significant effect of vitamin supplementation was observed on antioxidant
      enzymes activity.

PMID- 9553404
TI  - [Resumption of professional work after cerebral aneurysm surgery].
AB  - The influence of various factors upon the resumption of professional work was
      examined in the group of 87 patients, who had undergone an operation of single
      cerebral aneurysms. Professional activity was resumed by 59.9% members of the
      examined group. The age and the level of education or professional training were
      found to be the most influential factor. The location of aneurysms and sex of
      patients was found to have no influence. The fact that greater percent of those
      living in the country resumed their professional activities than those living in
      towns or cities can be explained by greater difficulty in to suffering was a
      quite frequent factor which can be overcome due to proper information given to
      the patients, thereby the greater number of patients can resume their
      professional career.

PMID- 9553403
TI  - [The influence of ischemia provoked by dobutamine and exercise on presence of
      late potentials in patients after myocardial infarction].
AB  - The aim of this study was to examine the influence of transient exercise- and
      dobutamine-induced myocardial ischemia on time domain parameters of signal
      averaged ECG (SAECG) and presence of late potentials (LP) in patients after
      myocardial infarction (MI). The investigation covered 85 patients after healing
      of MI, divided into two groups. Group I (24 males and 2 females, mean age 56.8 +/
      6.4 yrs) had exercise-induced ischemia and group II consisted of 59 patients (51
      males and 8 females, mean age 58.3 +/- 8.5 years) with ischemia provoked by the
      intravenous dobutamine stress-testing. In each patient 2-D echocardiography, 24-h
      ambulatory Holter ECG, coronary arteriography were performed before stress
      testing. The ischemia was proven by using Tc-99m MIBI myocardial perfusion and
      standard 12-lead ECG monitoring. Recordings of SAECG were registered at rest and
      during ischemia under influence of stress-testing. The following time-domain
      parameters of SAECG were analysed: the root-mean-square voltage of the last 40
      and 50 ms of the filtered QRS complex (RMS40, 50), total time duration of
      filtered QRS (t-QRS) and duration of signal lower than 40 muV (LPD). LP were
      detected when two or three of following criteria's had been registered: RMS 40 <
      20 muV, t-QRS > 114ms, LPD > 38s. There was no statistically significant
      differences in all time domain parameters of SAECG between records at the
      baseline and during ischemia in each study group. At the baseline LP have been
      registered in 11.5% and in 15% patients, respectively of group I and group II. On
      the top of ischemia during treadmill exercise stress-testing LP have been
      recorded in 27% subjects. Under influence of dobutamine-provoked ischemia LP have
      been registered in 25% patients. CONCLUSIONS: Exercise- and dobutamine-induced
      ischemia triggers development of LP in small grade in post-infarction patients.

PMID- 9553405
TI  - [Coronary disease and hormonal treatment during the perimenopausal period].
AB  - Hormone replacement therapy (HRT) is widely recognized as probably most advisable
      treatment of perimenopausal women with cardiovascular disorders. Whenever HRT is
      administered for gynecological reasons, special attention should be paid to the
      presence of cardiological risk factors as these may be potentiated by high doses
      of gestogens. The authors undertake this problem inspired by a cases of a 53
      years old patient (given oral lynestrol fair persisting uterine bleedings) who
      suffered from several complications, including venous thrombosis and myocardial
      infarction.

PMID- 9553407
TI  - [The significance of converting enzyme inhibitor angiotensin I to angiotensin II
      in treatment of patients with coronary disease].
AB  - Angiotensin-converting enzyme (ACE) inhibitors are now established drugs in the
      treatment of hypertension and heart failure. The renin-angiotensin-aldosterone
      system is complex and acts as a circulating hormonal system, a local endogenous
      tissue system and neuromodular. Current experimental evidence suggests that ACE
      inhibitors reduce the risk associated with atherosclerotic cardiovascular
      disease. The antiatherogenic action of ACE inhibitors is related to complex
      effects mediated by these agent, including an antiproliferative and antimitotic
      action, beneficial effects on endothelial function, plaque-stabilizing effects
      and the action of these agents on the sympathetic nervous system. The role of ACE
      inhibitors in preventing the clinical sequale of atherosclerotic cardiac disease
      has been evaluated in various patient populations. Several small trial assess the
      effects of ACE inhibitors in severity of angina pectoris have reported
      conflicting results, with benefit is some patients and no benefit or even
      exacerbation of angina in others, indicating that ACE inhibitors do not have
      consistent antianginal effects in short-term study. ACE inhibitors have the
      theoretical potential to prevent restenosis after PTCA but they do not prevent
      restenosis and has no effect on overall clinical outcome. New data suggest that
      ACE inhibitors may be effective therapy fir patients following acute myocardial
      infarction. The renin-angiotensin system, is activated during new myocardial
      infarction and has an impact on the process of remodeling of the left ventricle
      which causes ist dysfunction and heart failure. In most of the large mortality
      trials the rationale for early treatment with ACE inhibitors after myocardial
      infarction was stated. ACE inhibitors have a positive effect in preventing the
      ventricular dilatation and they reduce the rate of reinfarctions and the
      mortality rate.

PMID- 9553406
TI  - [A case of centroblastic lymphoma of the thyroid gland].
AB  - A case of a 49-year male patient with centroblastic lymphoma of the thyroid gland
      is presented. Centroblastic lymphoma was diagnosed with cytological and
      immunocytochemical examination of the biopsy specimen, and verified with
      histological examination of tumor section collector intraoperationally. Diagnosed
      tumor was classified as II AE degree. No signs of lymphocytic thyroiditis co
      existing with centroblastic lymphoma were noted. The patient was treated
      chemically with CBVPM/AVBP regimens for 8 months. Complete remission still
      lasting, i.e. 96 months after completion of chemotherapy, was achieved.

PMID- 9553408
TI  - [Combination therapy in primary hypertension].
AB  - Hypertension is an important risk factor for vascular disease. Primary goal of
      hypertension treatment is to prevent or delay the onset of blood pressure-related
      morbidity and mortality. It has been well demonstrated that the responses rate to
      any single class of antihypertensive agent, give as monotherapy is approximately
      45% to 55%, and in half of hypertensive population a second will be required. The
      data from clinical trials clearly demonstrate that two-drug combination, usually
      with low-dose diuretics with any one of the other first-line agents increases the
      response rate to about 80% to 85% and reduces the likelihood of adverse events
      and alteration in lipid, carbohydrate and electrolyte metabolism. Of the various
      combinations being given that of an diuretic and ACE inhibitor, and ACE inhibitor
      and non-dihydropyridine calcium channel blockers seems particularly attractive.
      Some combinations are inappropriate, such as diuretic and calcium channel
      blockers, and beta-blocker with verapamil and diltiazem. Combination of ACE
      inhibitor and a non-dihydropyridine calcium channel blockers may provide benefit
      in regression left ventricular hypertrophy diabetic nephropathy, and post
      myocardial infarction.

PMID- 9553409
TI  - [Use of beta-adrenoreceptor antagonists in treatment of patients with chronic
      heart failure].
AB  - Chronic heart failure (CHF) is present in 1-10% of the whole population. From the
      drugs used in CHF so far only angiotensin converting enzyme inhibitors and
      nitrate with hydralazine improved the survival which was caused by beneficial
      influence of these drugs on neurohormonal factors. There is growing interest in
      beta-blockers which are believed to stop the progress of CHF. Although the first
      attempts of using beta-blockers in the treatment of CHF took place in 70-ties,
      only recent years brought better understanding of mechanisms of their action. The
      beneficial effect of beta-blockers in CHF is related to their protective
      influence on myocardium and to hampering of apoptosis--programmed cell death--the
      phenomenon which is exaggerated in CHF. The investigations carried out in last
      years proved that carvedilol which is beta 1-, beta 2- and alpha 1-blocker and
      has antioxidant properties improved clinical status and reduced mortality in the
      cohorts of patients with all-cause CHF. At present great trials estimating
      various beta-blockers and comparing these drug among themselves are being
      conducted.

PMID- 9553410
TI  - [The influence of digitalis glycosides on certain neural and hormonal functions
      in patients with chronic heart failure].
AB  - Digitalis works not only as a positive agent in congestive heart but as a
      modulator of neurosecretion as well. Opposite to its positive inotropic activity
      the latter refers to small doses. It leads to restoring of the autonomic balance.
      Its effect is resulted from the increased vagal activity that suppresses the
      adrenergic tone. Disregulating of the neurosecreting system may occur in patients
      with left ventricular impairment even without symptoms of left ventricular
      failure. Digitalis then besides stimulating contractility stops the
      neurosecretion and may be used not only to improve hemodynamics but also to slow
      the process of progressive deterioration of cardiac function.

PMID- 9553411
TI  - [Right ventricular infarction].
AB  - Right ventricle infarction (RVI) is not a rare clinical entity. It complicates
      approximately half of inferolateral myocardial infarctions. Under the term RVI we
      can find mild, asymptomatic dysfunction of right ventricle and cardiogenic shock
      as well. RVI is associated with increased mortality and its presence obliged us
      to qualify patient to a high risk group. Diagnosis is based on clinical signs,
      electrocardiographic findings, hemodynamic measurements and echographic
      evaluations. The proper treatment of RVI requires support of right ventricle
      preload with fluid administration, maintainance of atrio-ventricular synchrony,
      reduction of right ventricle afterload. Early reperfusion with fibrinolytic
      therapy and coronary angioplasty should be regarded as the prior methods of
      treatment RVI. Patients who survive RVI have complete resolution of hemodynamic
      abnormalities with restoration of proper right ventricle function.

PMID- 9553412
TI  - [Retroperitoneal fibrosis and chronic peri-aortitis--new hypothesis].
AB  - Retroperitoneal fibrosis is characterised by the development of fibrotic mass
      surrounding the abdominal aorta and its branches. In the one third of cases, the
      causes of this disease include ergot-derivative drugs, retoperitoneal haemorrhage
      or urine extravasation and desmoplastic response to a variety of tumours.
      Retroperitoneal fibrosis is idiopathic in two thirds of cases and is found most
      commonly as an isolated fibrotic plague centered over the lumbar spine and
      entrapping one or both ureters. It has been postulated that fibrosis in
      idiopathic cases is caused by a chronic inflammatory or autoimmune response to
      antigens leaking into retroperitoneum from atheromatous plagues in the aorta or
      common iliac arteries. Many findings indicate the active nature of aortic
      adventitial chronic inflammation associated with human advanced atherosclerosis
      ("chronic periaortitis") and show its possible progressive potential to the
      clinically important disease termed "idiopathic retroperitoneal fibrosis" and
      "inflammatory aneurysm". A definitive differential diagnosis requires not only CT
      and NMR but also histologic confirmation. Treatment may be surgical or medical,
      with the best outcome observed in patient receiving both.

PMID- 9553413
TI  - [Axiomatic space of the physician's office].
AB  - Doctor's surgery is a space containing a number of meanings which are
      deliberately or unconsciously interpreted by the patient. Organization of that
      space, its material shape, affect a successful contact between the doctor and the
      patient, thanks to which a therapeutic aim is achieved.

PMID- 9553414
TI  - [Polish army hospital in Zeithain].
AB  - Polish Military Hospital in Zeithain was a prisoner-of-war hospital of Warsaw
      Insurgents. In the period from 13 October 1944 until 23 April 1945, in the
      hospital there were 1572 war prisoners, including 1029 sick and wounded. The
      hospital consisted of all wards, the operating theatre, X-rays unit and the
      laboratory. In August 1945 the hospital got repatriated.

PMID- 9553415
TI  - [Obsessive-compulsive disorders in childhood and adolescence].

PMID- 9553416
TI  - [Therefore force, when obsession is present?].
AB  - To force somebody means inflict pressure on him. Obsessive-compulsive behaviour
      (OCB) is a feature of relationships. In early infancy, repetitive biological
      functions rapidly become automatic psychic functions. Small children often try to
      relate to their surrounding in a constrained manner in order to re-establish
      their omnipotence. Play and transitional space are opposites of OCB. Anxiety and
      constraints show an inverse relation to each other. In many cases, OCB in infants
      and small children has no clinical relevance. OCB is characterised by a high
      intrapsychic persistence during the whole period of psychophysic development.
      Obsessive-compulsive diseases (OCD) may serve as defence against oedipal
      strivings or against psychotic functioning. It is addressed against the self, an
      inner object or a relevant person of the surrounding. OCD correspond to a
      relational illness. In this situation an involved person becomes rapidly involved
      in the constraint problem. To maintain an adequate form of relationship within
      such transferential movements, a continuous "unchaining" is necessary. During
      transference, regressive anxieties and rages are expressed in a personalised
      form. Verbalised by the therapist, they become ready for transformation. The
      relationship may now open up to allow the inclusion of a third person.

PMID- 9553417
TI  - [Obsessive-compulsive disorders in childhood and adolescence--recent
      psychoanalytic views and treatment approaches].
AB  - Based on neurobiological and development-psychological findings psychodynamic
      concepts for understanding compulsive disorders are supplemented and extended. A
      stimulus barrier impaired during development which in the early mother-child
      system normally develops into an autonomous and self-regulating ability has the
      consequence in compulsive disorders that the ability of drawing limits between
      reality and phantasy has only poor success. Based on case examples the function
      of the situation triggering the compulsive symptoms and the foreseeable
      relationship quality are examined on the different levels of development. Then it
      becomes clear how complex the originating conditions for compulsive disorders
      are, and under which conditions a primary object fails as original external
      psycho-neurobiological regulator in the development of autonomous self
      regulation.

PMID- 9553418
TI  - [Countertransference in psychoanalytic therapy of children and adolescents with
      obsessive-compulsive disorders].
AB  - Understanding countertransference in dynamic therapy of children and adolescents
      is important for the clarification of unconscious conflicts because of the
      frequent absence of dreams and free association in the analytic process. When
      compulsions determine the course of the psychic disorder countertransference
      becomes an important landmark for comprehending and resolving the affect-loaded
      sadomasochistic collusion as an externalization of intrapsychic conflicts.
      Compulsive acts and thoughts helping to preserve seriously threatened structures
      of the self and the ego engender different countertransference reactions in the
      analyst than the ego-superego-conflicts of compulsion neurosis. This makes them
      essential for diagnosis and therapeutic interventions.

PMID- 9553419
TI  - [Tuberculosis morbidity among children and adolescents in Udmurt Republic].

PMID- 9553420
TI  - [Tuberculosis as hospital acquired infection].
AB  - Tuberculosis morbidity rates were analyzed in the staff of antituberculosis
      dispensaries and institutions of the general therapeutical network. There were 74
      cases of tuberculosis among the medical workers in 1993-1996. The sociomedical
      characteristics of the medical staff suffering from tuberculosis are given. The
      findings show it necessary to refer tuberculosis to a group of hospital-acquired
      infections and to implement a package of prophylactic measures to reduce
      tuberculosis morbidity rates among medical workers, as well as to timely detect
      patients with tuberculosis at general hospitals. Measures for preventing
      tuberculosis are proposed for the personnel of therapeutical institutions.

PMID- 9553421
TI  - [Role of general somatic hospitals in replenishment of contingents of
      antituberculosis dispensaries].
AB  - The patients whom tuberculosis was detected at general somatic hospitals form 28%
      in the make-up of dispensary registry group IA. In these hospitals BC are found
      in those with suspected tuberculosis and even in its destructive forms (4-5.7%).
      Activization of explanatory work with physicians and nurses at a hospital has
      caused an increase in positive sputum tests for BC and favoured a 7-fold increase
      in their detection by bacterioscopy after Ziehl-Neelsen.

PMID- 9553422
TI  - [Detection of tuberculosis in infants and preschool children].
AB  - The paper analyzes 367 case histories of babies, infants and preschool children
      treated for local tuberculosis at a specialized pediatric unit in 1977-1996. It
      is ascertained that tuberculosis was detected in 55% of children on their
      referral for medical aid and in 45% on prophylactic examinations. Prophylactic
      examinations detected tuberculosis of the intrathoracic lymph nodes more
      frequently (72.7%) and primary tuberculosis less frequently (26.7%). On
      referrals, tuberculosis of the intrathoracic lymph nodes, primary tuberculosis,
      and other forms of pulmonary tuberculosis were diagnosed in 68.8, 25.0, 6.2%,
      respectively. When tuberculosis was identified on referrals, pulmonary
      tuberculosis was much more commonly complicated. To form a tuberculosis risk
      group and to make prophylactic antituberculosis measures are an inherent
      condition for early detection of tuberculosis.

PMID- 9553423
TI  - [Characteristics of tuberculosis process in new cases of pulmonary tuberculosis
      from different social groups of patients in relation to methods of disease
      detection].
AB  - Three hundred and eighty new cases of pulmonary tuberculosis were examined and
      the characteristics of a tuberculous process studied in different social groups
      (industrial and office workers, unemployed) in relation to methods of detection
      of the disease: on referrals or prophylactic examinations. There was a
      considerable reduction in the proportion of patients whose disease was detected
      on prophylactic examinations, and in the families of patients with tuberculosis.
      The tuberculous process detected on referrals was characterized by its higher
      prevalence and a qualitatively more severe form (caseous pneumonia, fibrinous
      cavernous, and cavernous processes). A decay phase and bacterial isolation were
      more frequently noted.

PMID- 9553424
TI  - [Spread of drug-resistant strains of mycobacterium tuberculosis among patients
      with isolated bacteria].
AB  - The paper provides the data on the spread of drug-resistant strains of
      Mycobacterium tuberculosis (MBT) among contingents of patients with pulmonary
      tuberculosis who have been registered at a dispensary and new cases. The spread
      was 42.5 and 20.0%, respectively. In the past 3 decades, the spread of primary
      (baseline) drug resistance of MBT has increased from 6.5 to 22.0%.

PMID- 9553425
TI  - [Diagnosis of tuberculosis in patients of pulmonological hospital].
AB  - Analysis of clinical forms of tuberculosis in patients of a pulmonological showed
      that 65.5% of them had infiltrative tuberculosis, 13.8% fibrocavernous
      tuberculosis, 10.4% disseminated tuberculosis, 6.9% focal tuberculosis, and 1.7%
      tuberculoma. It was ascertained that in these patients destructive tuberculous
      changes were common and occurred in 67.2% and tuberculosis was concurrent with
      other lung diseases in 70.7%. This follows that special attention should be given
      to the patients of pulmonological hospitals and sputum tests for mycobacteria are
      to be performed 3 times.

PMID- 9553426
TI  - [Potentialities of x-ray computed tomography in diagnosis and treatment by
      transthoracic paracentesis of caverns in tuberculosis].
AB  - The paper presents data on the use of computed tomography in transthoracic
      paracentesis of tuberculous caverns for diagnostic and therapeutical purposes.
      The topography of caverns, their size, the pattern of the cavernous wall, the
      degree of development and intensity of a fibrous layer were assessed from
      computed tomographic findings, which was a guide in choosing the procedure of
      paracentesis of the lung and topical treatment. The patency of draining bronchi
      was determined by computed tomography to choose instillations or spraying of
      antibiotics into the cavern. The possibility to determine the presence of
      intracavernous timbers, the extent of vessels in the adjacent tissue, that of
      pericavitary fibrosis and pleural commissures made it possible to locate the
      optimal point of paracentesis and to avoid possible complications, such as
      hemorrhage and pneumothorax. It is pointed out that computed tomography is shown
      in the first paracentesis of a cavern to determine its topography and at the end
      of treatment of establish the outcome of a cavernous process.

PMID- 9553428
TI  - [Clinical and laboratory diagnosis of primary tuberculosis of respiratory organs
      in adults].
AB  - Comprehensive clinical, X-ray, and laboratory studies were made of 495 patients
      with primary tuberculosis of respiratory tuberculosis whose age was over 18
      years. Tuberculosis of intrathoracic lymph nodes (a tumorous form), infiltrative
      tuberculosis at preroot and lower lobar sites), and exudative pleurisy were
      prevalent in the clinical structure of primary forms of a specific process. The
      highest morbidity was observed in the age group of 20-25 years. Tuberculin tests
      were positive in 95.1% of cases, they being hyperergic in 10.9% and negative and
      nuclear only in 4.9%. Sputum tests for altered forms of tuberculosis agents
      enhance diagnostic verification by 16%. The informative value of a complex of
      clinical and X-ray examinations in the diagnosis of primary respiratory
      tuberculosis in adults ranges from 47.4 to 79.6% with immunoassay, and 28.3 to
      77.5 with biochemical tests.

PMID- 9553427
TI  - [Difficulties in diagnosing pulmonary visceral forms of rheumatoid arthritis in
      tuberculous hospital].
AB  - The articulovisceral form of rheumatoid arthritis is severe, which creates
      difficulties in its diagnosis as it is characterized by polymorphism and atypical
      features. This type concurrent with pulmonary manifestations should be
      differentiated from inflammatory lung diseases, including tuberculosis.

PMID- 9553429
TI  - [Some problems in diagnosis of peripheral lymph nodes tuberculosis].
AB  - The structure of lymphadenopathies has been determined by biopsies of peripheral
      lymph nodes. The parameters are different in general and specialized
      prosectorship. Malignant diseases (34.0%), reactive hyperplasias (24.3%), and
      tuberculosis (only in 6.0%) were verified in the general prosectorship.
      Tuberculosis was detected in 61.3% at the phthisiological center. The problems of
      diagnosis of lymphadenopathies of various etiology are discussed.

PMID- 9553430
TI  - [Complications of polychemotherapy for renal tuberculosis].
AB  - The paper analyzes the incidence of adverse reactions caused by tuberculostatics
      used in the treatment of renal tuberculosis by follow-ups of 117 patients.
      Current polychemotherapy for renal tuberculosis has been found to be complicated
      by drug intolerance in 40.1% of cases. Intermittent intravenous injection of
      tuberculostatics causes side effects in 36.8% of patients while conventional
      treatment does in 59.1%. Pyrazinamide, streptomycin, and ethambutol are most
      toxic to patients with renal tuberculosis. There is a higher likelihood of drug
      intolerance in females with bilateral nephrotuberculosis complicated by chronic
      renal failure.

PMID- 9553432
TI  - [Endobronchial laser therapy in the surgery of pulmonary tuberculosis].
AB  - Endobronchial helium-neon laser therapy was used in 80 patients to undergo
      surgical intervention. For evaluation of the efficiency of laser therapy, the
      patients were divided into 2 groups: 1) 50 patients with chronic destructive
      pulmonary tuberculosis and 2) 30 with postoperative bronchopulmonary
      complications. A control group included 80 patients with the similar processes.
      Laser therapy used Group 1 patients expanded indications for surgical
      intervention. The resections of the lung made in led to postoperative
      complications in 32% of Group 1 patients and in 63% of the controls. Laser
      therapy in Group 2 patients promotes sanitation of the bronchial tree by
      enhancing the efficiency of reoperations by 18% than in the control group.

PMID- 9553431
TI  - [Blood ozonation in the treatment of patients with progressive pulmonary
      tuberculosis concurrent with diabetes mellitus].
AB  - Twenty nine patients with progressive pulmonary tuberculosis in the presence of
      diabetes mellitus were examined. Fifteen of them (a main group) had an additional
      course of intravenous dissolved ozone once 6-8 days (4 mg/ml per 400 ml of
      isotonic sodium chloride). By the end of month 2, 7 patients stopped massive
      bacterial expiration, which correlated with clinical improvement while a control
      group (n = 14) showed no clinical and laboratory changes. Following 3 months, 3
      control patients stopped massive bacterial expiration. At month 6, 11 patients of
      the main group also did this, decay cavities became close in 8 patients while in
      the controls, these figures were 8 and 7, respectively. The use of systemic blood
      ozoning eliminated chemotherapy resistance and accelerated abacillation and
      healing in the decay cavities. The mechanism of action of dissolved ozone is
      discussed.

PMID- 9553433
TI  - [Surgical treatment of bilateral pulmonary tuberculosis].
AB  - Two hundred and eighty two patients with different types of bilateral tuberculous
      lesion of the lung were operated on. Most (n = 124) patients underwent
      consecutive operations, 106 one-stage resections of the lung through transsternal
      access on the one side and video thoracoscopic resections on the other. One-stage
      bilateral video thoracoscopic operations were made in 52 cases. The greatest
      number of postoperative complications was noted with multistage operations, which
      is accounted for a critically ill patient group, advanced processes, concurrent
      pyoseptic infection. The patients undergone-transsternal resections showed
      minimum mortality rates with a rather low incidence of postoperative
      complications.

PMID- 9553434
TI  - [Use of antiseptic myramistin in the multimodality treatment of nonspecific
      suppurative pleuropulmonary diseases].
AB  - To treat patients with suppurative diseases of the bronchi, lung, and pleura, the
      new aseptic myramistine was topically applied as 0.005% myramistine solution in
      isotonic sodium chloride solution in 28 patients with acute and chronic pleural
      empyema, acute abscess of the lung, and suppurative endobronchitis-complicated
      bronchoectatic disease. The therapy made it possible to arrest the intoxication
      syndrome, to achieve abacillation of contents in the cavities of empyema,
      abscesses, and bronchoectases, to cure endobronchitis, to obliterate destructive
      cavities in the lung more rapidly and to prepare patients for a planned surgical
      intervention more valuably and to improve the results of surgical treatment. The
      studies allow the antiseptic myramistine to be recommended for topical treatment
      of pyodestructive diseases of the lung.

PMID- 9553435
TI  - [Effectiveness of extracorporeal ultraviolet blood irradiation in patients with
      chronic obstructive bronchitis].
AB  - The use of extracorporeal ultraviolet blood radiation (EUVBR) in the treatment of
      67 patients with chronic obstructive bronchitis (COB) showed some specific
      features of the clinical course of bacterial complications of the basic process.
      With EUVBR, most patients exhibited normal temperatures, less signs of
      intoxication and coughing, and rare rale in the lung than in the controls. A most
      objective criterion for the efficiency of EUVBR was a marked increase in the
      forced expiratory volume per sec after the first 3 procedures, which improved the
      patients' condition, diminished exercise-induced dyspnea. The hemogram of the
      patients undergone EUVBR in combination with antibiotic therapy indicated a
      substantial drop in erythrocyte sedimentation rates following the first 3
      procedures. The growth of pathogenic and opportunistic microbes from the sputum
      showed a great (10-fold) reduction when EUVBR and antibiotic therapy were
      concurrently used. The findings suggest that EUVBR has high therapeutical
      benefits in the treatment of COB.

PMID- 9553436
TI  - [Plasmid profile of mycobacteria spread on the territory of the Russian
      Federation].
AB  - The plasmid profile of different species of mycobacteria vegetating in the
      Russian Federation was first studied. All the drug-resistant mycobacterial
      strains of tuberculosis were found to be truly polyresistant. There was a certain
      association between the plasmid carriage and the high viability of the
      mycobacterial population in nontuberculous mycobacteria.

PMID- 9553437
TI  - [Diagnostic values of polymerase chain reaction test in females with genital
      tuberculosis].
AB  - The previously offered procedure for detecting. Mycobacterium tuberculosis, which
      is based on the polymerase chain reaction (PCR), has been tested for diagnosing
      genital tuberculosis in females. PCR was used to examine endometrial curettage
      specimens in 44 patients with different nosological entities, which showed a high
      sensitivity (80%) and a high specificity in the diagnosis of genital
      tuberculosis.

PMID- 9553438
TI  - [Method of resection and spondylocorporoplasty of lumbar and sacral vertebrates
      in experiments].
AB  - For a considerable reduction of injuries caused by resection and spondylodesis of
      the lumbosacral region of the spine, the authors have developed a procedure of
      conservation of vascular extravertebra and neural nets by employing 10 cadavers.
      With this the transabdominal approach is used to form an aperture in SI and
      partially LV corpus vertebralis, by removing all pathological substances of the
      healthy spongious substance of the bone. The formed cavity is filled by two
      autografts, bone bits, antibiotics and hemostatic sponge. The two autografts are
      formed as a cross and their ends are clung to the edge of the entrance aperture
      of the bone. Stitches are placed to the periosteum and the strata of the
      abdominal wall.

PMID- 9553439
TI  - [Detection rate of organochlorine pesticides and viral hepatitis B markers in
      patients with pulmonary tuberculosis].
AB  - Three hundred and fifty six patients with active forms of pulmonary tuberculosis
      were studied for organochlorine pesticides (OCP) and viral hepatitis B markers
      (VHBM) in their body. A combination of OCP and VHBM was detected in 37.4%, 63.2
      and 61.5% had OCP and VHBM, respectively. Detection rates for pesticides and VHBM
      were not related to the place of residence (town or village) or the clinical type
      of pulmonary tuberculosis. However, the blood levels of OCP were significantly
      higher in rural patients and in patients with advanced pulmonary tuberculosis
      than in urban patients and in patients with restrictive pulmonary tuberculosis.

PMID- 9553440
TI  - [Influence of mycobacterium on adaptive rearrangement in guinea pigs long exposed
      to polycystic aromatic hydrocarbon-containing agents].
AB  - Experiments on different groups of guinea pigs inoculated with Mycobacterium
      tuberculosis (MBT) and intact guinea pigs who received coal refining products and
      control ones indicated that long exposure to coal-tar resin enhanced mobilization
      of methionine from the liver with its accumulation in the lung and hematopoietic
      organs, increased the biosynthesis of arginine in the liver and its accumulation
      in the lung and hematopoietic organs. MBT drastically enhanced the exchange of
      the metabolites accumulated in the organs and prevented the formation of adaptive
      reactions to long-term exposure to polycyclic aromatic hydrocarbons at the level
      of membranous metabolism.

PMID- 9553441
TI  - [Laparoscopic diagnosis of abdominal organs tuberculosis].

PMID- 9553442
TI  - [A case of breast tuberculosis in patients with disseminated pulmonary
      tuberculosis].

PMID- 9553443
TI  - [Difficulties and errors in diagnosing of tuberculous meningitis and
      meningoencephalitis].

PMID- 9553444
TI  - [Contribution of Aspergillus fungi to the development of bronchopulmonary
      pathology (literature review)].

PMID- 9553445
TI  - Evolution, growth, and status of managed care in the United States.
AB  - While under attack in the United States, managed care/competition is being viewed
      by a number of European and other countries as a remedy in their struggle to
      control rising health care costs. While many fundamentals of American managed
      care have their roots in the British health system, significant differences exist
      between the two systems. While managed care, which can be loosely defined as any
      system of delivering health services in which care is delivered by a specified
      network of providers who agree to comply with the care approaches established
      through a case management process, has had a 100-year history in the United
      States, it wasn't until the mid-1970's that it began to gain national
      recognition. All health maintenance organizations (HMOs) are managed care
      organizations (MCOs) but not all MCOs are HMOs. The two other categories of MCOs
      are, preferred provider organizations (PPOs) and point of service plans (POS).
      Currently, three-quarters of Americans with health insurance are enrolled in
      managed care plans and there are 160 million Americans enrolled in such plans. A
      major on-going debate occurring in the United States is in regard to the
      comparative quality of care provided by MCOs and traditional fee-for-service
      plans. The study results to date have been equivocal. Another controversial
      managed care issue is the use of gag clauses in contracts between the MCOs and
      their providers. These clauses limit providers from being totally open and honest
      with patients about, for example, alternative treatment possibilities or the
      details of provider reimbursement. Since the failure of U.S. health care reform
      in 1994, there has been a more focused turn to the marketplace to provide the
      impetus for reducing costs. As a result, health care plans and providers have
      become more like traditional businesses which must focus on the bottom line to
      survive. In a marketplace where purchasers of care look for low bidders, it
      should be remembered that the level and quality of care a society receives is
      usually commensurate with the level of resources that it is willing to expend.

PMID- 9553446
TI  - Systematic review of case-control studies: oral contraceptives show no effect on
      melanoma risk.
AB  - BACKGROUND: Parallel to the rising incidence of malignant melanoma in fair
      skinned populations, intensive efforts are currently devoted to identifying risk
      factors for melanoma in addition to the well-known cutaneous factors and those
      variables related to UV-exposure. OBJECTIVE: Systematic review of published
      results to elucidate the role of oral contraceptives in the development of
      malignant melanoma. DATA SOURCES: Literature retrieval systems MEDLINE and
      CANCERLIT as well as reference lists of already collected studies. STUDY
      SELECTION: All 18 (non-duplicate) case-control studies on the above relationship.
      DATA EXTRACTION: From the published data, study-specific odds ratios (OR) and
      accompanying confidence intervals (CI) were recalculated. For a quantitative meta
      analytical summarisation two different models have been applied: a "fixed
      effects" (FE) and a "random effects" (RE) model. DATA SYNTHESIS: Study-specific
      ORs ranged from 0.13 up to 1.85; however, the majority of studies (14 of 18)
      yielded similar ORs within the interval [0.82, 1.15]. The summary ORs estimated
      from FE- and RE-models were both 0.95 (95% CI: [0.87, 1.04] for the FE-model,
      [0.87, 1.05] for the RE-model). CONCLUSION: The systematic review of case-control
      studies revealed no evidence for an aetiological role of oral contraceptives in
      the development of malignant melanoma.

PMID- 9553447
TI  - Blood pressure among immigrants to Israel from areas affected by the Chernobyl
      disaster.
AB  - OBJECTIVES: To validate and analyze apparent association of hypertension with
      exposures to radiation at Chernobyl among immigrants to Israel from the
      contaminated areas. METHODS: Data were collected in 1991 and 1994 from two
      samples of persons who immigrated to Israel from the contaminated zone around the
      Chernobyl nuclear power plant. The first sample were self-referred for evaluation
      in a clinic by whole-body cesium measurement, physical examination, and
      questionnaire (N = 756, 328 from less exposed and 438 from more exposed areas).
      The second wave data were collected in 1994 during home interviews for evaluation
      of psychosocial factors associated with their experience (N = 708, 121 from more
      exposed and 253 from less exposed areas). In the second study a referent group
      was included (n = 334) who were matched by age, sex, and year of immigration who
      immigrated from other areas outside of the contaminated zone. Estimates of
      exposure were based on the IAEA map of ground-level cesium isotope (137Cs)
      contamination. RESULTS: In the 1991 sample, 21% from high exposure areas and 16%
      from less exposed areas had elevated systolic blood pressure (> 140 mmHg).
      Elevated diastolic blood pressure (> 90 mmHg) had a similar difference between
      more and less exposed groups (21% and 16%). Age- and sex-specific analyses showed
      that statistically different levels were found in the older age groups. In the
      1994 sample, we confirmed a relationship between exposure and elevated blood
      pressure. 33% of those from the more exposed areas and 34% of those from less
      exposed areas had elevated systolic blood pressure, compared with 23% of the
      comparison group, with a similar trend found in diastolic blood pressure. The
      relationship between exposure and blood pressure was accentuated in the group of
      respondents who had high scores on PTSD symptoms. Of the psychological variables
      analyzed, systolic blood pressure was most strongly related to cancer-related
      anxiety and somatization. A discriminant function analysis showed that three
      variables: age, reporting a significant loss from the Chernobyl accident, and
      fear of cancer correctly differentiated 72% of those with normal and high blood
      pressure. CONCLUSIONS: There is a relationship between exposure to Chernobyl and
      high blood pressure, partly due to the psychological reactions to the accident.

PMID- 9553448
TI  - [Septic thrombophlebitis of the internal jugular vein and Lemierre syndrome].
AB  - The authors report a case of Lemierre's syndrome. This uncommon clinical entity
      is characterized by a septic internal jugular vein thrombosis with secondary
      metastatic abscesses and Fusobacterium necrophorum septicemia, following an acute
      oropharyngeal infection. The diagnosis is primarily clinical and it should be
      suspected when a severe septicaemic illness, with pulmonary symptoms, occurs
      after an acute pharyngotonsillar infection. This article reviews the clinical
      picture, microbiology and treatment of this forgotten complication of acute
      tonsillitis.

PMID- 9553449
TI  - [The focus in neonatology].
AB  - During the last years, neonatology has greatly improved. In the last decade,
      mortality and morbidity have decreased: mortality from respiratory failure of
      prematurity has decreased from 22% to 12%, mortality of the very low birthweight
      infants under 1000 g fell from 56% to 35% and mortalities related to asphyxia
      have diminished from 21% to 12% and to malformations from 33% to 28%. Prematurity
      is now the first cause of neonatal mortality. During this period, the number of
      babies under 1000 g has increased 4-fold and the number of multiple births
      increased more than 2-fold from 3% to 7% of the live births of our hospital.
      Attitudes towards the premature infant have changed, especially towards the
      extremely small (called the micropremies). The number of disabled children has
      increased in parallel with the better survival of the very immature newborns who
      till recently were not resuscitated.

PMID- 9553450
TI  - [Treatment of shoulder dislocation and the prevention of its recurrence].
AB  - Shoulder dislocation is a frequent pathology with a high level of recurrences
      especially in young patients. One week immobilization in a Dessault dressing is
      sufficient if it is followed by free mobilization avoiding external rotation and
      abduction. A 6 weeks rehabilitation program seems to prevent recurrences.

PMID- 9553451
TI  - [The role of apoptosis during craniofacial development: concepts and importance
      in pathology].
AB  - Apoptosis is an essential common final pathway in numerous pathological
      conditions such as malignant tumors, HIV-related CD4 lymphocytes degeneration,
      neurodegenerative disorders, and in programmed cell death events during normal
      embryogenesis. Some teratogenic substances for man and laboratory mammals induce
      an increase of the apoptotic phenomenon, responsible for the occurrence of some
      precise cranio-maxillo-facial malformations. The study of cell death during
      normal or teratogenic embryonic development allows to analyse the cellular
      mechanisms implied in the control of the apoptotic phenomenon, together with its
      dysregulation ending in pathological processes. We review the cell death
      phenomenon during cephalogenesis, both during normal embryogenesis, or in
      teratogenic conditions known to induce cranio-maxillo-facial malformations.

PMID- 9553452
TI  - [Meloxicam].
AB  - NSAID's are currently medications widely prescribed. Meloxicam is a new oxicam
      which has a low COX-2/COX-1 ratio, i.e. it has an inhibitory effect focused on
      the inflammatory proteins (COX-2) with relative saving of the homeostatic
      proteins (COX-1). This molecule has been studied in three rheumatic diseases, the
      acute flare-up of osteoarthritis, rheumatoid arthritis, and ankylosing
      spondylitis. The results show that meloxicam is as effective as comparative
      NSAID's. A global analysis of the data from more than 5000 patients included in
      clinical trials showed that gastro-intestinal tolerance of meloxicam was better
      than that of comparative NSAID'S. Nevertheless, the clinical translation of the
      anti-COX-2 selectivity concept is currently debated.

PMID- 9553453
TI  - [Requested euthanasia].

PMID- 9553454
TI  - [Death with dignity in cancer patients].

PMID- 9553455
TI  - [Death and HIV infection].

PMID- 9553456
TI  - [3 problem areas for the treating physician].

PMID- 9553457
TI  - [Therapeutic compliance].

PMID- 9553458
TI  - [Coronary stents].

PMID- 9553459
TI  - [Recent chest pain].

PMID- 9553461
TI  - [Why a burn center at the Vaud University Hospital Center?].

PMID- 9553462
TI  - [Initial resuscitation of the severely burned adult].

PMID- 9553464
TI  - [Metabolic and nutritional support of the adult burned patient].

PMID- 9553463
TI  - [Burns: etiology, diagnosis and surgical treatment].

PMID- 9553465
TI  - [Particularities of resuscitation in the burned child].

PMID- 9553466
TI  - [Burns of the hand].

PMID- 9553467
TI  - [Treatment of the severely burned patient with cultured autologous epidermis: the
      experience at Lausanne].

PMID- 9553468
TI  - [Living epidermal and dermal substitutes for treatment of severely burned
      patients].
AB  - Epidermal and dermal cells can be multiplied in vitro using different techniques.
      Under particular conditions, the structure and the function of the original
      tissues are partly recreated. Autologous epidermal substitutes for wound coverage
      in deep burns are prepared in less than three weeks. Bilayered skin equivalents
      containing a dermal component are obtained by growing epidermal cells on a
      reconstructed dermal substitute or by juxtaposing stratified cultures of
      keratinocytes and fibroblasts. New technologies are required to optimise the
      nutrition of three-dimensional cultures of skin cells, which should lead to
      further progress in the area of skin reconstruction.

PMID- 9553469
TI  - [Basic principles for correcting late burn sequelae].

PMID- 9553470
TI  - [Psychology of the severely burned patient].

PMID- 9553471
TI  - [Psychiatric approach to the severely burned patient].

PMID- 9553472
TI  - [Degree 3: a new association].

PMID- 9553473
TI  - [The misunderstanding of the diagnosis somatoform pain: a plea for a
      phenomenologic approach to pain].

PMID- 9553474
TI  - [Abdominal trauma].

PMID- 9553475
TI  - [Abdominal trauma].
AB  - While a great part of the Anglo-American medical literature addresses the topic
      of penetrating trauma the German speaking countries rather publish on blunt
      abdominal injury. The presented paper discusses the strategic principles of acute
      clinical management of abdominal trauma on the combined basis of own research
      results and a comprehensive review of the literature. Blunt abdominal injuries in
      most cases from a part in the pattern of multiple trauma. The early, first-hours
      mortality is most often caused by severe traumatic brain injury or abdominal
      trauma with massive hemorrhage. The prehospital management of penetrating
      injuries is characterized rather by the concept of 'load and go', whereas the
      onscene stabilization of the patient with blunt abdominal injury should precede
      transport to the adequate hospital. On arrival in the accident and emergency room
      an immediate blood transfusion is recommended for hemodynamically unstable
      patients. If then a stabilization is not achieved, an emergency laparotomy should
      follow. Abdominal stab injuries should be explored by laparoscopy if an
      intraperitoneal lesion is suspected. If then the possibility of an intestinal
      lesion is present a laparotomy should be performed directly thereafter. Firearm
      injuries require open revision in almost all cases. The standard diagnostic
      technique in blunt abdominal trauma is sonography, assisted by computed
      tomography and, if indicated, angiography in hemodynamically stable patients.
      Isolated abdominal injuries without hemodynamic or coagulation disorders allow
      conservative treatment in the intensive care setting. In severe multiple trauma
      as well as in manifest shock even the smallest fluid detection should lead to
      laparotomy. The surgical treatment of splenic rupture is still a matter of
      discussion. Splenectomy is indicated in patients with severe concomitating
      injuries or shock whereas in the remainder of cases the total or partial
      preservation of the spleen should be pursued. Hepatic injuries offer a broad
      spectrum of operative interventions, ranging from superficial hemostatic measures
      over compression techniques like 'packing' and 'mesh-wrapping' to atypical and
      anatomical resections and to liver transplantation in exceptional cases. Lesions
      of tubular organs and the pancreas pose especially difficult diagnostical
      problems but regularly allow a rather easy operative treatment.

PMID- 9553476
TI  - [Late outcome of severed extensor tendons in the area of the hand and fingers].
AB  - In the care and further treatment of patients with hand injuries, a necessary
      requirement of the hand surgeon is that he be able to cope with the interlocking
      factors that are no longer influential, for example, the type and extent of the
      trauma or the age of the patient; the influential factors are a thought-out care
      plan, atraumatic action with regard to optimal restoration of the hand. This also
      showed a retrospective analysis of results and post-examination from flexor
      tendon injuries in the hand of 298 patients, who were surgically cared for from
      1984 to 1994 at the surgical clinic of the University of Jena. Of the 298
      patients 119 patients with 198 flexor tendon injuries (165 fingers and 33 thumbs)
      were followed up. For objective assessment of the treatment results, the
      assessment scheme Buck-Gramcko was used.

PMID- 9553477
TI  - [Os odontoideum. Etiology, clinical aspects, therapy].
AB  - The etiology of os odontoideum is still controversial. In most patients, it is
      found by accident because of neurological symptoms and/or painful range of motion
      of the cervical spine. Upon recognition of the os odontoideum, it is unknown
      whether or not immediate surgery is beneficial. This is in contrast to an
      "unstable" os odontoideum, which could result in atlantoaxial instability or
      compression of the myelon. In this study, we present the results of our treatment
      of four patients with an unstable os odontoideum. In all four cases, a C1-2
      fusion was performed (3 x Magerl/Seemann, 1 GallieBrooks). Postoperatively, we
      found a complete regression of neurological symptoms in three patients and one
      was significantly improved. The range of motion of the cervical spine was free of
      pain in all patients. As a result, we strongly support immediate surgical
      treatment of an unstable os odontoideum in order to prevent severe and life
      threatening neurological complications.

PMID- 9553479
TI  - [Epiperiostal, percutaneous plate osteosynthesis. A new minimally invasive
      technique with reference to "biological osteosynthesis"].
AB  - Conservation of bone perfusion, protection of the soft tissue envelope and
      reduction of systemic stress by strengthening the host defence mechanism are
      general and essential aspects of a biological osteosynthesis. The minimal
      invasive operating techniques with the use of technical aids and tricks form the
      necessary presupposition for successful bone healing with a low complication
      rate. For an epiperiosteal, percutaneous plate osteosynthesis, the technique
      using a sliding tip and a manipulation handle is demonstrated.

PMID- 9553478
TI  - [Clinical effects of supplemental enteral nutrition solution in severe
      polytrauma].
AB  - Previous studies in critically ill patients have shown the beneficial effects of
      early enteral nutrition supplemented with arginine, omega-3 fatty acids and
      nucleotides (Impact) on immunological response, infection rate and length of stay
      in hospital. No specific data exist for patients with severe multiple injury, who
      represent a high risk group for systemic inflammatory response syndrome (SIRS),
      septic complications and multiple organ failure (MOF). In this prospective,
      randomized, double-blind controlled clinical study on patients after severe
      trauma (ISS ca. 40) the primary study endpoints were incidence of SIRS and MOF
      [definitions according to Am Soc Crit Care Med (5) and Goris (23), Sauaia (43)].
      Thirty-two patients enrolled in the study, and 29 were eligible for analysis:
      test (Impact) (n = 16), control (n = 13). Both groups were comparable according
      to age, body mass index and severity of trauma (PTS-test: 38.8 +/- 12.5, PTS
      control: 40.8 +/- 15.5, ISS-test: 39.6 +/- 11.4, ISS-control: 40.5 +/- 9.2).
      Patients were randomized to receive either Impact (test) or an isonitrogenous
      isocaloric diet (control). Feeding was started on the 2nd day after trauma via
      endoscopically placed nasoduodenal or jejunal feeding tubes. The experimental
      diet was safe and well tolerated. During the 1st week the enteral feeding amount
      was about 2000 ml without significant difference. Test-fed patients developed
      SIRS significantly less frequently between day 1 and day 28 (8 vs 13.3; P < 0.05)
      and especially between day 8 and day 14 (3 vs 6.2; P < 0.001). In the control
      group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10,
      11, 16 and 17 and the Sauaia score on days 8, 9, 10 and 11 (P < 0.05; P < 0.01).
      Mortality rate did not significantly differ (test 2/16, control 4/13), nor did
      length of ICU or hospital stay. With regard to the acute-phase response, C
      reactive protein was significantly lower on day 4 in the test group (test: 131 +/
      67 mg/l, control: 221 +/- 110 mg/l) as was fibrinogen on day 12 (6.6 +/- 1.4 vs
      7.5 +/- 1.4 g/l) and day 14 (7.1 +/- 1.3 vs 7.8 +/- 0.8 g/l). No significant
      difference could be observed for CD4/CD8 ratio, CD45 isotope on activated T-cells
      and lymphocytic interleukin (II)-2-receptor- and II-6 level. However, HLA-DR
      antigen presentation on peripheral monocytes was significantly elevated on day 7
      in the test group (P < 0.05). According to the results, arginine, omega-3 fatty
      acids and nucleotides-enriched diet during early enteral feeding leads to
      reduction of SIRS after severe multiple injury. There is evidence for improvement
      of post-traumatic immunological response which helps to overcome the
      immunological depression after trauma.

PMID- 9553480
TI  - [Riding injuries and injuries due to handling horses in experienced riders].
AB  - A group of experienced riders who qualified for the German riding badge 9.5 years
      ago answered a questionnaire pertaining to injuries during jumping, dressage and
      cross-country riding, as well as handling the horse. During riding 69% of the
      persons had had 187 injuries and while handling the horse 52% had had 124
      injuries. Fractures and contusions were the most-frequent injuries; most riding
      injuries were located in the upper extremities and shoulder while handling mainly
      in the hands and feet. The number of injuries was comparable in jumping, dressage
      or cross-country riding. The time engaged in jumping was about one-third of the
      other types of riding, but the injuries were more severe. While handling the
      horse the number of injuries relative to the time spent during the activity were
      higher but less complicated. No change in safety precautions had been implemented
      by 67% of the persons injured. The injury rate for equestrians is relatively low
      both in handling the horse and during riding. The frequent fractures and
      contusions may be reduced by following the required safety regulations.

PMID- 9553481
TI  - [Traumatologic emergency in the shock department. Analysis of the spectrum and
      temporal aspects of diagnostic imaging].
AB  - With a prospective assessment of 140 emergency-room patients, we registered the
      conventional radiological examinations (CR), ultrasound (US) and computer
      tomographies (CT), including the duration of the examinations, transportation and
      diagnostic free time. RESULTS: CR: 98.6% (average 8.5 radiographs per patient),
      US 78.6%, CT 67.8%. DURATION: CR average 20.3 min (range 1-80 min), US average
      6.5 min (range 2-15 min), CT average 16.9 min (range 12-135 min). The entire time
      spent in the primary diagnostic work-up, including CT: average 79.4 min (only CR
      and US average 49.1 min). Diagnostic free time, including CT: average 31.9 min,
      without CT average 19.2 min. Time for transportation and repositioning: average
      14.5 min. When a CT is indicated, the radiological diagnostic work-up will
      increase as a result of waiting and transportation. The patient also suffers
      because of more repositioning procedures.

PMID- 9553482
TI  - [Diagnosis and therapy of ligament injuries of the foot].

PMID- 9553483
TI  - [Performance-related income budget. A means for reorganizing hospital financing].
AB  - Performance-related budgets are the result of negotiated performance units per
      hospital multiplied by state-wide negotiated prices. Such hospital budgets
      contain profit chances and loss risks. Exceeding the contractual fixed amount
      leads to price reductions, falling below that amount leads to lower
      reimbursement. A consistent pricing system for basic and department performance
      units could solve the present problem of cost separation in Germany. A step in
      this direction is the definition of hospital department groups and the
      construction of an average department treatment case, which could be priced on an
      average cost base. In the long run, more flexibility according to pricing and
      budgeting can be developed. Competitive insurance companies should be free to
      find their own budgets so that a hospital can have several independent
      contractors.

PMID- 9553484
TI  - [Considerations of biomechanics after clavicular resection. Case report of rower
      with Ewing sarcoma].
AB  - Because of poorly compartmentalized paraclavicular soft tissues, total
      extraperiostal claviculectomy in cases of malignoma with cortical destruction is
      always marginal. Due to different muscular compensation in the patients examined,
      literature disagrees on the biomechanical consequences of claviculectomy for the
      shoulder girdle. We present a case of total clavicula resection including
      chemotherapy and radiation in an 18-year-old rower with Ewing's sarcoma. Sixteen
      month postoperative radiological and clinical examination revealed an excellent
      result. Thirty-six months postoperatively the patients is able to row symptom
      free without any evidence of the disease. Biomechanical reflections on the
      significance of the trapezius muscle in compensating thoracoscapular instability
      provide information for rehabilitation.

PMID- 9553485
TI  - Quantifying HIV-1 RNA without amplification.

PMID- 9553486
TI  - The nanoliter niche. NMR detection for trace analysis and capillary separations.

PMID- 9553487
TI  - Keeping U.S. water programs in check.

PMID- 9553488
TI  - Microminiaturized immunoassays using atomic force microscopy and compositionally
      patterned antigen arrays.
AB  - This paper combines the topographic imaging capability of the atomic force
      microscope (AFM) with a compositionally patterned array of immobilized antigenic
      rabbit IgG on gold as an approach to performing immunoassays. The substrates are
      composed of micrometer-sized domains of IgG that are covalently linked to a
      photolithographically patterned array of a monolayer-based coupling agent. The
      immobilized coupling agent, which is prepared by the chemisorption of
      dithiobis(succinimidyl undecanoate) on gold, is separated by micrometer-sized
      grids of a monolayer formed from octadecanethiol (ODT). The strong hydrophobicity
      of the ODT adlayer, combined with the addition of the surfactant Tween 80 to the
      buffer solution that is used in forming the antibody-antigen pairs, minimizes the
      nonspecific adsorption of proteinaceous materials to the grid regions. This
      minimization allows the grids to function as a reference plane for the AFM
      detection of the height increase when a complementary antibody-antigen pair is
      formed. The advantageous features of this strategy, which include ease of sample
      preparation, an internal reference plane for the detection of topographic
      changes, and the potential for regeneration and reuse, are demonstrated using
      rabbit IgG as an immobilized antigen and goat anti-rabbit IgG as the
      complementary antibody. The prospects for further miniaturization are discussed.

PMID- 9553489
TI  - Randomly ordered addressable high-density optical sensor arrays.
AB  - Array-based sensors provide an architecture for multianalyte sensing. In this
      paper, we report a new approach for array fabrication. Sensors are made by
      immobilizing different reactive chemistries on the surfaces of microspheres.
      Sensor arrays are prepared by randomly distributing a mixture of microsphere
      sensors on an optical substrate containing thousands of micrometer-scale wells.
      The sensors occupy a different location from array to array; thus the identity of
      each sensor is ascertained and registered on the detector using encoding schemes,
      rather than by a predetermined location in the array. The approach thereby shifts
      the demand from fabrication to signal processing. The availability of commercial
      image analysis software makes such a shift both cost-effective and time
      efficient.

PMID- 9553490
TI  - Classification and quantitation of 1H NMR spectra of alditols binary mixtures
      using artificial neural networks.
AB  - A pattern recognition method based on artificial neural networks (ANNs) to
      analyze and quantify the components of six alditol binary mixtures is presented.
      This method is suitable to classify the spectra of the 15 mixtures obtained from
      the six alditols and to produce quantitative estimates of the component
      concentrations. The system is user-friendly and is helpful in solving the problem
      of greatly overlapping signals, often encountered in NMR spectroscopy of
      carbohydrates. A "classification" ANN uses 200 intensity values of the 1H NMR
      spectrum in the range 3.5-4 ppm. When the correct mixture is identified, the
      quantification is solved by assigning a specific ANN to each mixture. These ANNs
      use the same 200 values of the spectrum and output the values of the two
      concentrations. The error in the ANN responses is studied, and a method is
      developed to estimate the accuracy in determining the concentrations. The
      networks' abilities to recognize previously unseen mixtures are tested. When the
      classification ANN (trained on the 15 binary mixtures) is exposed to complex
      (i.e., more than binary) mixtures of the six known alditols, it successfully
      identifies the components if their minimum concentration is 10%. Given the
      precision of the results and the small number of errors reported, we believe that
      the method can be used in all fields in which the recognition and quantification
      of components are necessary.

PMID- 9553491
TI  - Screening ligands for membrane protein receptors by total internal reflection
      fluorescence: the 5-HT3 serotonin receptor.
AB  - The screening of ligands for membrane receptor proteins is central to the
      discovery of new pharmaceutical drugs. We present a general method to reversibly
      attach receptor proteins via an affinity tag to a quartz surface and subsequently
      detect with high sensitivity the real-time binding of ligands by total internal
      reflection fluorescence. A serotonin-gated ion channel protein was immobilized,
      and the binding of a fluorescent ligand was investigated. The affinity and the
      kinetic parameters of binding were measured, and the effect of unlabeled
      compounds was determined by competition. The pharmacology of the immobilized
      receptor was identical to that of the native receptor. The affinity of unlabeled
      ligands was rapidly and effectively determined. The method described here is
      generally applicable for membrane proteins and opens new ways for the discovery
      of pharmacologically active compounds.

PMID- 9553492
TI  - Surface-enhanced Raman gene probe for HIV detection.
AB  - We report, for the first time, the use of surface-enhanced Raman (SERS)-active
      labels for primers used in polymerase chain reaction amplification of specific
      target DNA sequences. This method has the potential for combining the spectral
      selectivity and high sensitivity of the SERS technique with the inherent
      molecular specificity offered by DNA sequence hybridization. The effectiveness of
      the detection scheme is demonstrated using the gag gene sequence of the human
      immunodeficiency virus. The potential use of multiple probes for simultaneous
      detection of multiple biological targets is discussed.

PMID- 9553493
TI  - The potential of restricted access media columns as applied in coupled-column
      LC/LC-TSP/MS/MS for the high-speed determination of target compounds in serum.
      Application to the direct trace analysis of salbutamol and clenbuterol.
AB  - This study investigated the potential of restricted access media (RAM) columns
      used as a first column in coupled-column LC hyphenated to thermospray tandem mass
      spectrometry (LC/LC-TSP/MS/MS) for the fast, selective, and sensitive
      determination of target drugs in serum samples. Because of their wide range in
      polarity, salbutamol and clenbuterol were chosen as model compounds and
      representatives of the class of beta 2-agonists. Three types of RAM columns were
      tested: (i) Pinkerton ISRP (internal surface reversed phase, 5 microns), (ii) SPS
      (semipermeable surface, 5 microns C18), and (iii) RP-18 ADS (alkyl-diol silica,
      25 microns). A 3-micron C18 column (50 mm x 4.6 mm i.d.) was chosen as the second
      column. Tandem mass spectrometric detection was carried out in the selected
      reaction monitoring (one parent-->one daughter) mode. With regard to retention
      and, moreover, the peak elution volume of the analytes, the ISRP material was
      found to perform best: a 50-mm x 4.6-mm i.d. ISRP column in combination with a
      100% aqueous buffer (pH of 7.0 +/- 0.2) allowed the injection of large volumes
      (up to 200 microL) of sample without additional band broadening of the analytes
      and provided sufficient preseparation between analytes and large-molecule serum
      constituents. Under the selected conditions, both analytes could be determined in
      serum samples up to a limit of quantification (LOQ) of 0.5 ng/mL, with a sample
      throughput of 7 and 5 h-1 for salbutamol and clenbuterol, respectively. Method
      validation was carried out by analyzing, in the course of several days, calf and
      human serum samples spiked with the analytes. In the case of salbutamol, the
      overall recovery from serum samples spiked at levels between 0.5 and 50 ppb (n =
      33) was 103.4%, with a repeatability of 12.7% and reproducibility of 14.3%. The
      overall recovery for clenbuterol was 99.6% (n = 15, spiked level 0.5-5 ppb), with
      a repeatability of 15.2% and reproducibility of 16.4%. The adopted LC/LC-TSP/MS/
      MS analyzer appeared to be very robust under the selected conditions, and, after
      the period of analysis involving the processing of more than 100 mL of serum,
      neither loss of chromatographic performance nor pressure increase of columns or
      of the interface was observed.

PMID- 9553494
TI  - Ion trap mass spectrometry for kinetic studies of stable isotope labeled vitamin
      A at low enrichments.
AB  - The role of beta-carotene in chemoprevention of cancers and other chronic
      diseases generated controversy when subpopulations taking beta-carotene
      supplements showed increased mortality in clinical trials. Determination of the
      dynamics of beta-carotene in individual human subjects has emerged as a high
      priority. Stable isotope labeled beta-carotene tracers can be employed to
      determine rates of conversion to retinol (vitamin A), but tracer doses must be
      small to minimize perturbation of endogenous retinoid and carotenoid pools. In
      such cases, ratios of labeled tracer/endogenous retinol are often low, and
      quantitative analysis at enrichments of < 1 mol% are unreliable owing to ion
      molecule reactions that generate ions at the same mass as the labeled tracer even
      when no tracer is present. The current study demonstrates improved gas
      chromatography/mass spectrometry quantification of retinol-d4 and unlabeled
      retinol, as their tert-butyldimethylsilyl ethers, at low enrichments using an ion
      trap mass spectrometer operated in selected ion storage mode. Electron ionization
      of analyte takes place in the ion trap using conditions that eject ions outside
      the range m/z 390-420, and molecular ions at m/z 400 and 404 from retinol and
      retinol-d4 are quantified. Using this approach, unlabeled retinol yields a signal
      close to values calculated from natural isotopic abundances (approximately
      0.13%), whereas several quadrupole instruments operated using selected ion
      monitoring yielded 2-5 times greater signal when no labeled retinol was present.

PMID- 9553495
TI  - Chiral separations using dipeptide polymerized surfactants: effect of amino acid
      order.
AB  - Chiral separations using various polymerized dipeptide surfactants in
      electrokinetic capillary chromatography (EKC) are investigated. The two main
      dipeptide surfactants used in this study were sodium N-undecylenyl-L-valine-L
      leucine (L-SUVL), and sodium N-undecylenyl-L-leucine-L-valine (L-SULV). These
      studies were performed in order to determine if the order of amino acids in
      dipeptide surfactants is important in terms of chiral recognition and
      separations. Both the monomer and the polymer of these two surfactants were
      compared for the separation of two model atropisomers, (+/-)-1,1-bi-2-naphtol
      (BOH) and (+/-)-1,1'-bi-2-naphthyl-2,2'-diyl hydrogen phosphate (BNP). Some
      advantages and disadvantages of the polymer relative to the monomer are
      discussed. Four other surfactants, the polymers of sodium N-undecylenyl-L-leucine
      L-leucine (L-SULL), sodium N-undecylenyl-L-valine-L-valine (L-SUVV), sodium N
      undecylenyl-L-valine (L-SUV), and sodium N-undecylenyl-L-leucine (L-SUL), were
      also used in this study, and their performance was compared to that of poly(L
      SULV). These data show conclusively that the order of amino acids in dipeptide
      surfactants has a dramatic effect on chiral recognition. Our investigations
      indicate that poly-(L-SULV) provides the best enantioselectivity among the four
      dipeptide and two single amino acid surfactants for the separation of BNP and
      BOH. The advantages of poly-(L-SULV) are demonstrated via the ultrafast
      separation of the enantiomers of BNP and BOH in less than 1 min.

PMID- 9553496
TI  - A matrix for DNA separation: genotyping and sequencing using
      poly(vinylpyrrolidone) solution in uncoated capillaries.
AB  - We report a new sieving matrix for DNA separation based on commercially available
      poly(vinylpyrrolidone). The new sieving matrix has a very low viscosity at
      moderate concentrations, e.g., 27 cP at 4.5%. Its excellent self-coating property
      can reduce electroosmotic flow to a negligible level. Column regeneration between
      runs is very simple and effective. Successful separations were achieved in
      uncoated capillaries. For genotyping, we show that D1S80 and amelogenin sex
      determination system can be baseline separated as double-stranded DNA, and vWF,
      TH01, TPOX, and CSF1PO short tandem repeats can be separated with single-base
      resolution as single-stranded DNA in this new matrix. Sequencing of M13mp18
      showed good resolution up to 500 bases in a solution of high-molecular-weight
      fraction extracted from commercially available PVP. The feasibility of adaptation
      to a multicapillary array system is discussed.

PMID- 9553497
TI  - Capillary zone electrophoresis of bile acids with indirect photometric detection.
AB  - Investigations in our laboratory have demonstrated that capillary zone
      electrophoresis (CZE) with indirect photometric detection is a viable approach to
      the separation and identification of free bile acids along with their taurine and
      glycine derivatives. Various parameters such as pH, organic solvent
      concentrations, column temperature, and type of chromophore electrolyte were
      investigated to optimize the electrophoretic separation and to maximize the peak
      capacity. The quality of separation of bile acids can be dramatically improved by
      incorporating gamma-cyclodextrin (gamma-CD) in the running electrolyte. This
      improvement in resolution is accompanied by a decreased migration time,
      suggestive of an increase in association of gamma-CD with bile acids. As a
      result, a CZE separation of all 15 bile acids was possible in approximately 30
      min using 5 mM adenosine 5'-monophosphate, 7 mM gamma-CD in 75% (v/v) methanol at
      pH 7.0.

PMID- 9553498
TI  - Evaluation of association constants between drug enantiomers and human alpha 1
      acid glycoprotein by applying a partial-filling technique in affinity capillary
      electrophoresis.
AB  - The principles for evaluation of conditional association constants between drug
      enantiomers and proteins, exemplified here by alpha 1-acid glycoprotein (AGP),
      using capillary zone electrophoresis employing a partial filling technique, is
      presented. In the partial filling technique only the first part of the capillary
      is filled with the selector, and this selector zone (plug) length can be varied
      by introducing the selector solution at different times at constant pressure. An
      important feature of the technique is the low consumption of selector solution in
      this study only 40-290 nL is used per run, of special importance when the
      availability of the selector is limited, and also in case it is expensive.
      Conditions are chosen so that the protein has a net negative charge and migrates
      toward the anode, while the analytes migrate toward the detector at the cathodic
      side. The resolution is linearly related to the effective plug length, as shown
      in separations of the enantiomers of disopyramide and remoxipride. The effective
      plug length can be calculated, which forms the basis to apply this technique for
      determinations of association constants. The association between the enantiomers
      of the solutes and AGP varied with increasing temperature, as shown by determined
      association constants. It was found that the association between the enantiomers
      and AGP was strongest at 25 degrees C and decreased at both lower and higher
      temperatures. This unexpected finding may indicate conformational changes of the
      protein with temperature variations.

PMID- 9553499
TI  - Aesthetic considerations for maxillary obturators retained by implants.
AB  - Maxillary obturators are prostheses used to replace maxillary tissues, missing
      congenitally or removed by trauma or tumor ablative surgery. These prostheses are
      used to restore function (speech, swallowing, and mastication) and aesthetics. A
      considerable number of edentulous patients have difficulty in retaining this type
      of prosthesis. Utilization of osseointegrated dental implants is a significant
      adjunct in treating these cases, but it must be undertaken with careful planning
      to ensure predictable aesthetic results. The learning objective of this article
      is to discuss the technique of designing aesthetic maxillary prostheses supported
      by osseointegrated dental implants. The discussion includes indications and
      contraindications, and a postcarcinoma surgery case is used to illustrate the
      clinical procedure.

PMID- 9553500
TI  - Search for metal-free restorations: a combination of ceramic optimized polymer
      and a fiber-reinforced composite.

PMID- 9553501
TI  - The aesthetic and endodontic dilemmas of calcific metamorphosis.
AB  - Traumatic injuries to dentition can initiate either a resorptive or calcific
      pulpal response. In the sequelae of calcific degeneration, the clinical crown
      frequently becomes discolored, requiring an aesthetic correction to restore the
      tooth to its natural color. Four potential solutions are currently available to
      achieve this goal. The learning objective of this article is to describe the
      etiology of calcific metamorphosis, discuss the four potential solutions, and
      present the responses of endodontists polled as to the treatment indications.
      While the posterior dentition may experience the identical pathologic response to
      trauma and crown discoloration, this article focuses on the restoration of the
      anterior dentition. Several cases are presented to illustrate the four treatment
      modalities, and recommendations for follow-up of traumatic injuries are
      indicated.

PMID- 9553502
TI  - Management of temporomandibular disorders in a restorative practice.
AB  - Various disorders related to the masticatory muscles or to the temporomandibular
      joints may be encountered in a restorative dental practice. Most of them can be
      managed by the restorative dentist whose primary interest may not lie in the area
      of temporomandibular disorders. The term temporomandibular disorders is used in
      this discussion to denote the group of diseases of the masticatory system that
      involves primarily the temporomandibular joints, the masticatory muscles, and the
      occlusion of the teeth. The learning objective of this article is to describe
      temporomandibular disorders encountered in general practice. Managing these
      disorders in the general practice of restorative dentistry is not difficult and
      adds to the comfort of the patient and possibly to the success of the
      restorations.

PMID- 9553503
TI  - Myofascial trigger points of pain.

PMID- 9553504
TI  - The milled implant-supported prosthesis: a treatment alternative for the
      edentulous mandible.
AB  - The milled implant-supported prosthesis offers the benefits of fixed and
      removable restorations. Its infrastructure provides the same rigidity as the
      fixed restoration, due to the precise fit to the superstructure that is removable
      to promote adequate access for hygiene, yet provides lip support and maintains
      close contact with the soft tissues. These advantages enhance phonetics,
      aesthetics, correct lip support, and maintenance. The learning objective of this
      article is to discuss the indications for milled implant-supported restorations,
      review the scientific background of materials and techniques utilized, and
      describe the clinical and laboratory procedures involved. An uncomplicated and
      cost-effective impression technique is outlined, and the numerous steps of infra-
      and superstructure fabrication are presented.

PMID- 9553505
TI  - Functional versus aesthetic articulation of maxillary anterior restorations.
AB  - The correct orientation of the master model is a frequently overlooked aspect of
      communication between the clinician and the ceramist. The master model must
      provide the ceramist with the same perspective of the patient as is seen by the
      clinician--facing the viewer. Unless precise information is transferred to the
      laboratory, the ceramist can only estimate horizontal and vertical alignment of
      the working cast from landmarks taken from the cast itself. It is unwise to leave
      such appraisal to chance, especially when restoring multiple anterior
      preparations, where the potential for misalignment of the cast increases with the
      number of restorations involved. The learning objective of this article is to
      discuss communication techniques between the clinician and the ceramist for
      achieving precise and predictable orientation in the treatment of aesthetic
      anterior restorations.

PMID- 9553508
TI  - Payment. Capitation is catching.

PMID- 9553506
TI  - Rehabilitation of an edentulous mandible with an implant-supported prosthesis.
AB  - The advances in osseointegration have resulted in an increased utilization of
      implants for restoration of the edentulous jaw. The success of osseointegrated
      implants supporting full arch prostheses has become more predictable. All implant
      restorations require a thorough diagnosis and a definitive treatment plan.
      Following a diagnostic wax-up, an optimal surgical implant template must be
      fabricated; it serves as a guide or prescription for placement of implants in an
      optimal anatomic location. The slightest misangulation of an implant may create
      restorative limitations. In such circumstances, alteration of the restorative
      design or selection of alternate materials may be required. The learning
      objective of this article is to review the fabrication of a combined ceramometal
      and resin-metal fixed/removable implant-supported mandibular hybrid prosthesis.
      Diagnosis, surgical template fabrication, vertical dimensions, buccal/lingual
      space limitations, and aesthetics are discussed.

PMID- 9553509
TI  - Finance. Some gains, some pains.

PMID- 9553510
TI  - Consumer polls. Another break with tradition.

PMID- 9553511
TI  - AIDS Czarina. Interview by Theresa Hudson.

PMID- 9553512
TI  - Fraud storm surges toward HMOs.

PMID- 9553513
TI  - 6 new buying rules.
AB  - Times change--and so does software purchasing. Buying in bulk, paying top dollar
      for what a system does, trusting a vendor to watch out for you--that's old input.
      Here are six fresh rules for the buying game.

PMID- 9553514
TI  - 3 forces for change.
AB  - For decades, health care has nursed a distrust of comparative clinical data. But
      what the market wants, it gets. Economics, technology, and the spirit of the
      times call for computer systems that measure quality.

PMID- 9553515
TI  - 10 CEO resources.
AB  - With computer woes marching into the front office and onto the front page these
      days, it's time to bone up. This guide to books, Web sites, and other executive
      resources will get you started.

PMID- 9553516
TI  - It's worth the ... risk.
AB  - Sharing risk with HMOs requires the patience of a kindergarten teacher, the
      finesse of a U.N. negotiator, and the agility of a fighter pilot. Intimidated
      yet? Neither are these executives. Our exclusive data show how hospitals handle
      risk contracts.

PMID- 9553517
TI  - Answers from the audit trail.
AB  - It's a lot cheaper to develop a compliance plan than fight fraud charges. Trouble
      is, off-the-shelf wisdom is hard to come by. Here's sage advice from compliance
      pros on how to put your plan in motion.

PMID- 9553518
TI  - A fight for poor eyes ... and other battles for the outpatient market.

PMID- 9553519
TI  - Can mergers save these markets?

PMID- 9553520
TI  - Managed care. Sierra's military maneuver.

PMID- 9553521
TI  - Medical devices. Label fable?

PMID- 9553522
TI  - End-of-life care. Plan B for pain code.

PMID- 9553523
TI  - Rural health care. Wheeling and healing.

PMID- 9553524
TI  - Phen-fen fallout. Financial side effects.

PMID- 9553525
TI  - Hip fractures are an increasingly important public health problem.

PMID- 9553526
TI  - The effects of adduction and abduction on the length of the limb in fractures of
      the neck of the femur. 1884.

PMID- 9553527
TI  - Circumstances of falls causing hip fractures in the elderly.
AB  - A prospective analysis was performed on 832 patients to determine the
      circumstances surrounding falls leading to hip fracture within a homogeneous,
      elderly urban population. Special emphasis was placed on the season of year, time
      of day, location of fall, and other circumstances in which the fracture occurred.
      All patients were community dwelling, cognitively intact, previously ambulatory
      elderly who sustained a femoral neck or intertrochanteric fracture. Most
      fractures occurred at home, particularly in patients who were older, less
      healthy, and poorer ambulators. More than 75% of fractures resulted from a fall
      while the patient was standing or walking. Most falls occurred during daylight
      hours with a peak seen in the afternoon. No seasonal variation in the incidence
      of hip fractures was observed.

PMID- 9553528
TI  - Medical management of osteoporosis. Fracture prevention.
AB  - The current medical treatment for the prevention of fractures in patients with
      osteoporotic bone, in particular, in patients with fractures involving the hip is
      discussed. Four drugs, calcium, calcitonin, estrogen, and alendronate have been
      approved for marketing by the Food and Drug Administration for the treatment of
      osteoporosis. Each of these drugs has a different mode of action to prevent bone
      loss and each carries its own side effects which must be weighed against the
      benefits. The future of medical management of osteoporosis involves designing new
      drugs that will reduce bone loss, potentially restore bone mass, and show proven
      efficacy in preventing fractures.

PMID- 9553529
TI  - Predictors of functional recovery after hip fracture in the elderly.
AB  - Three hundred thirty-eight community dwelling, ambulatory, elderly patients who
      sustained a hip fracture were observed prospectively to determine which patient
      and fracture characteristics at hospital admission predicted functional recovery
      at 3, 6, and 12 months. Multiple logistic regression was performed to estimate
      the simultaneous contributions of the predictor variables to failure of
      functional recovery. Before sustaining a fracture, 16% of patients were dependent
      on basic activities of daily living and 46% were dependent on instrumental
      activities of daily living. By 1 year after fracture, 73% of the patients had
      recovered to their basic activities of daily living status before fracture
      whereas only 48% had recovered to their instrumental activities of daily living
      status before fracture. Patients who were age 85 years or older, who lived alone
      before sustaining a fracture, and who had one or more comorbidities were at
      increased risk of delay or failure in recovering basic activities of daily
      living. Only instrumental activities of daily living independence before fracture
      predicted failure to recover instrumental activities of daily living function by
      3 and 6 months after fracture. At 1 year, patient age 85 years or older was the
      only predictor of failure to recover instrumental activities of daily living
      function that existed before fracture. Based on characteristics at admission, a
      group of patients at high risk for failure to recover basic activities of daily
      living function within 1 year of sustaining a hip fracture can be identified.

PMID- 9553530
TI  - Functional outcome after hip fracture in Japan.
AB  - One thousand one hundred sixty-nine elderly Japanese patients who sustained a hip
      fracture were observed prospectively. Ninety-two percent had operative fracture
      treatment. Hospital length of stay averaged 67 days; 81% of patients were
      discharged to their place of residence where they resided before sustaining the
      fracture. Mortality rates at 120 days, 1 year, and 2 years after injury were 6%,
      11%, and 19%, respectively. At 1-year followup, ambulatory status was recovered
      to that of the level experienced before injury in 67% of patients.

PMID- 9553531
TI  - Functional outcome after hip fracture. Effect of general versus regional
      anesthesia.
AB  - The effect of anesthetic technique on ambulation and functional recovery after
      hip fracture was studied in a series of 631 community dwelling, elderly patients.
      Functional recovery at followup was determined by an 11-item functional rating
      scale. In univariate analysis, recovery of ambulatory ability and percent
      functional recovery were significantly higher at 6 months for patients who had
      general anesthesia. When controlling for potential confounding variables,
      however, no differences were observed in recovery of ambulatory ability or
      percent functional recovery between the two groups at 3, 6, or 12 months after
      hip fracture.

PMID- 9553532
TI  - Norian SRS cement augmentation in hip fracture treatment. Laboratory and initial
      clinical results.
AB  - Bone quality, initial fracture displacement, severity of fracture comminution,
      accuracy of fracture reduction, and the placement of the internal fixation device
      are important factors that affect fixation stability. New high strength cements
      that are susceptible to remodeling and replacement for fracture fixation may lead
      to improved clinical outcome in the treatment of hip fractures. Norian SRS is an
      injectable, fast setting cement that cures in vivo to form an osteoconductive
      carbonated apatite of high compressive strength (55 MPa) with chemical and
      physical characteristics similar to the mineral phase of bone. It can be used as
      a space filling internal fixation device to facilitate the geometric
      reconstruction, load transfer, and healing of bone with defects and/or fractures
      in regions of cancellous bone. Furthermore, this cement can improve the
      mechanical holding strength of conventional fixation devices. Use of this
      material potentially could improve fracture stability, retain anatomy during
      fracture healing and improve hip function, thus achieving better clinical
      outcomes. In vivo animal studies have shown the material's biocompatibility, and
      cadaveric studies have shown the biomechanical advantage of its use in hip
      fractures. Initial clinical experience (in 52 femoral neck fractures and 39
      intertrochanteric fractures) showed the potential clinical use of this innovative
      cement in the treatment of hip fractures.

PMID- 9553533
TI  - Outcome after hemiarthroplasty for femoral neck fractures in the elderly.
AB  - A prospective outcome study was performed on 270 patients, 65 years of age and
      older, who sustained a femoral neck fracture and underwent hemiarthroplasty. The
      treatment compared was the use of a noncemented unipolar versus either a cemented
      or a press fit bipolar prosthesis. The outcome variables assessed included the
      occurrence of a postoperative complication, length and cost of hospitalization,
      and function in various quality of life measurements. Patients who underwent
      bipolar hemiarthroplasty with either a cemented or a press fit prosthesis had
      better pain relief and function than patients who had a noncemented unipolar
      prosthesis at a minimum of 24 months after surgery. However, the mean
      hospitalization cost for patients who had a bipolar prosthesis was $12,290
      compared with $8876 for a unipolar prosthesis.

PMID- 9553534
TI  - Eight-year outcome associated with clinical options in the management of femoral
      neck fractures.
AB  - This study involved a review of the medical records of 367 patients treated
      surgically after femoral neck fracture. Linkage of these records with claims
      files from the Health Care Financing Administration allowed as many as 8 years of
      followup to analyze the rates of hospital readmission rates for revision, other
      postoperative complications and mortality. The results revealed: (1) a
      significantly higher revision rate was associated with internal fixation for the
      treatment of displaced femoral neck fractures in patients older than 80 years of
      age; no differences in revision rates were seen between internal fixation or
      hemiarthroplasty for the treatment of nondisplaced femoral neck fractures in this
      patient age group; (2) no differences in revision rates were found between
      internal fixation or hemiarthroplasty for the treatment of displaced femoral neck
      fractures in patients between the ages of 65 to 80 years; (3) a significantly
      higher mortality rate was associated with internal fixation than hemiarthroplasty
      for patients who were between the ages of 65 and 80 years; and (4) no differences
      in medical or surgical complications, revision rates, or other outcomes were
      found between unipolar and bipolar prostheses, or between anterior and posterior
      surgical approaches for hemiarthroplasty in patients who were age 65 years or
      older.

PMID- 9553535
TI  - Unipolar versus bipolar hemiarthroplasty for the treatment of femoral neck
      fractures in the elderly.
AB  - This paper presents the short term results of an ongoing prospective randomized
      trial comparing a cemented unipolar with a cemented bipolar hemiarthroplasty for
      the treatment of displaced femoral neck fractures in the elderly. Forty-seven
      patients with an average age of 77 years completed 6-month followup. Outcomes at
      6 weeks, 3 months and 6 months were assessed by completion of a patient oriented
      hip outcome instrument and by functional tests of walking speed and endurance. No
      differences in the postoperative complication rates or lengths of hospitalization
      were seen between the two groups. Patients treated with a bipolar
      hemiarthroplasty had greater range of hip motion in rotation and abduction and
      had faster walking speeds. However, no differences in hip rating outcomes were
      found. These early results suggest that use of the less expensive unipolar
      prosthesis for hemiarthroplasty after femoral neck fracture may be justified in
      the elderly.

PMID- 9553536
TI  - Stress fractures of the femoral neck.
AB  - Stress fractures of the femoral neck are uncommon injuries. In general these
      injuries are seen in two distinct populations: (1) young, healthy, active
      individuals such as recreational runners, endurance athletes, or military
      recruits; and (2) the elderly who have osteoporosis. Stress fractures can be
      classified as either fatigue or insufficiency fractures and result from untoward
      cyclic loading or impaired bone quality. The key to treatment is early diagnosis,
      which may require scintigraphy or magnetic resonance imaging. Nondisplaced
      compression type stress fractures can be treated nonoperatively with protected
      weight-bearing and frequent radiographic followup. Tension type stress fractures
      should be stabilized internally to prevent the adverse consequences of fracture
      displacement.

PMID- 9553538
TI  - Intramedullary versus extramedullary fixation for the treatment of
      intertrochanteric hip fractures.
AB  - One hundred thirty-one patients (135 fractures) who sustained an
      intertrochanteric fracture were assigned randomly to treatment with either a
      sliding hip screw or an intramedullary hip screw and followed up prospectively.
      In patients with unstable intertrochanteric fractures, the intramedullary device
      was associated with 23% less surgical time and 44% less blood loss; however, use
      of the intramedullary hip screw in patients who had a stable fracture pattern
      required 70% greater fluoroscopic time. Intraoperative complications occurred
      exclusively in patients in the intramedullary hip screw group. There were no
      differences in the rates of functional recovery between the two fixation groups.

PMID- 9553537
TI  - Comparison of the compression hip screw with the Medoff sliding plate for
      intertrochanteric fractures.
AB  - The Medoff sliding plate was designed to achieve compression along the femoral
      neck and the longitudinal axis of the femoral shaft theoretically to improve the
      treatment of intertrochanteric hip fractures. The Medoff sliding plate was
      compared with a standard compression hip screw in a randomized, prospective study
      for the fixation of 160 stable and unstable intertrochanteric fractures with an
      average followup of 9.5 months (range, 6-26 months). Overall, 91 fractures were
      treated using the compression hip screw and 69 were treated with the Medoff
      sliding plate. Stable fracture patterns (46) united without complication in both
      treatment groups. Unstable fractures (114) had an overall failure rate of 9.6%,
      14% (nine patients) with the compression hip screw and 3% (two patients) with the
      Medoff plate; this difference was significantly different. The time to union for
      the 114 unstable fractures was not significantly different between the two
      devices. For all patients, no differences in lengths of hospitalization, return
      to ambulatory status before fracture, postoperative living status, or
      postoperative pain was observed between the two device groups. Use of the Medoff
      plate for all fracture types was associated with a significantly higher amount of
      blood loss and operating time.

PMID- 9553539
TI  - Use of an interlocked cephalomedullary nail for subtrochanteric fracture
      stabilization.
AB  - Forty-five Russell-Taylor Type 1B subtrochanteric femoral fractures were
      stabilized using an interlocked cephalomedullary nail. The intraoperative
      complication rate was 13.5%; the most frequent complication was a varus
      malreduction. The union rate was 100% at an average of 13.5 weeks after surgery;
      there were no implant failures. Forty-three of 45 (96%) patients regained greater
      than 120 degrees knee motion. Based on these results it is thought that an
      interlocked cephalomedullary nail may be the implant of choice for stabilization
      of Russell-Taylor Type 1B fractures; however, its proper use requires careful
      intraoperative technique, with particular attention given to avoid a varus
      malreduction.

PMID- 9553541
TI  - Magnetic resonance imaging of the shoulder in abduction.
AB  - To simulate the painful arm position in subacromial impingement syndrome,
      magnetic resonance imaging of the shoulder was done with the arms at the sides
      and at 80 degrees abduction in two groups of patients. Group A had 20 shoulders
      in 20 patients with subacromial impingement syndrome and Group B had 19 shoulders
      in 19 patients without impingement syndrome. When arm position was changed from
      adduction to abduction, an increase in signal intensity of the rotator cuff
      tendon was seen more often in Group A (45%) than in Group B (26%). Group A
      shoulders showed encroachment of the acromion or the acromioclavicular joint to
      the rotator cuff in 25% of the shoulders with the arms at the sides, and in 75%
      with the arms in abduction. Similar findings were observed in only 14% and 21% of
      Group B shoulders in the respective arm positions. Abduction of the arms seemed
      to cause encroachment of the overlying structure, especially of the
      acromioclavicular joint, to the rotator cuff in patients with subacromial
      impingement syndrome, even if there were no such findings in the images with the
      arms at the sides.

PMID- 9553540
TI  - Different ways to treat subtrochanteric fractures with the Medoff sliding plate.
AB  - Thirty-two consecutive subtrochanteric fractures in 32 patients were stabilized
      using the Medoff sliding plate and were followed up prospectively for 1 year. Two
      patients died during the first postoperative year. Twenty-nine of the remaining
      30 (97%) fractures united by 1-year followup. Two types of plate dynamization
      schema were used: uniaxial (17 patients) and biaxial (15 patients). With uniaxial
      dynamization, plate sliding averaged 12 mm along the femoral shaft without
      medialization of the femoral shaft. With biaxial dynamization along the femoral
      shaft and the neck, plate sliding averaged 11 mm and screw in barrel sliding
      averaged 9 mm; medialization of the femoral shaft ranged from 0% to 35% of the
      femoral shaft diameter. Three fractures treated with uniaxial dynamization had
      migration of the lag screw within the femoral head; all three fractures united
      without additional screw migration after secondary or staged biaxial plate
      dynamization.

PMID- 9553542
TI  - Anteroposterior instability of the distal clavicle after distal clavicle
      resection.
AB  - Resection of the lateral end of the clavicle disrupts the acromioclavicular
      articulation and creates the potential for abnormal postoperative motion.
      Seventeen isolated distal clavicle resections were reviewed to assess translation
      of the acromioclavicular articulation in the anteroposterior plane and its
      relationship to patient outcome. Stress radiographs were used to quantitate the
      translation of the distal clavicle and the amount of bone resected. Radiographs
      of the contralateral shoulder served as a control. Patients completed a
      questionnaire on shoulder function and pain and were examined preoperatively and
      postoperatively. The total translation (anterior plus posterior) in the
      anteroposterior plane averaged 8.7 mm (range, 3-21 mm) for surgically treated
      shoulders and was significantly greater than that for the contralateral shoulders
      (mean, 3.2 mm; range, 1-6 mm). Patients' postoperative visual analog pain scales
      correlated with the magnitude of anteroposterior translation. The amount of
      translation and the postoperative pain scores did not correlate with the apparent
      joint space seen on radiographs after surgery. The correlation of pain scores
      with the amount of translation shows that excessive anteroposterior instability
      of the distal clavicle can cause postoperative shoulder pain and poor surgical
      outcome.

PMID- 9553543
TI  - Subcoracoid dislocation of the distal end of the clavicle. A case report.
AB  - Subcoracoid dislocation of the outer end of the clavicle in association with an
      acromial fracture is a rare injury usually produced by high energy trauma that
      moves the clavicle posterior to the conjoined tendon and inferior to the coracoid
      process. To restore the acromioclavicular joint, open reduction is needed. After
      the reduction is accomplished, the clavicle has to be stabilized with a
      coracoclavicular screw. The acromial fracture can be reduced and held with
      nonabsorbable sutures placed through the bone. To avoid osteolysis of the distal
      end of the clavicle and to be able to repair the torn ligaments, treatment should
      not be delayed.

PMID- 9553545
TI  - Assessment of neuroforaminal decompression in degenerative spinal stenosis.
AB  - Surgical decompression of spinal stenosis is a balance between adequate removal
      of bone and soft tissue for an effective decompression of neural structures and a
      sufficient retention of bone to maintain mechanical stability of the spine. To
      develop an objective, reproducible technique for the assessment of neuroforaminal
      decompression in the adult lumbar spine, facet sparing laminectomies were
      performed from L1-S1 on the lumbar spines of 59 human cadavers. A series of
      semirigid probes in 0.5-mm increments were passed into each successive
      intervertebral foramen bilaterally, beginning at L2-L3. The minimum space
      available for the nerve root within the foramen of the lumbar spine is 3.5 mm at
      L2-L3, 3.9 mm at L3-L4, 4.3 mm at L4-L5 and 5.1 mm at L5-S1, as determined by
      three independent observers. There were no significant differences in
      interobserver or intraobserver measurements. There were no complications related
      to passage of the probes. This study provides a method for the intraoperative
      determination of the adequacy of neuroforaminal decompression.

PMID- 9553544
TI  - Functional laboratory assessment after oncologic shoulder joint resections.
AB  - A laboratory evaluation was undertaken to assess the shoulder range of motion and
      distal strength after oncologic resection and reconstruction involving the
      shoulder joint and to compare these functional parameters based on potentially
      important variables. Inclusion in the study was limited to 32 patients with bone
      tumors of the proximal humerus or scapula treated surgically by resection of the
      shoulder joint including the proximal humerus from 1976 through 1992. Active
      shoulder range of motion and isometric elbow extension and forearm supination
      strength are significantly less after surgery in patients with greater amounts of
      bony resection and with resection of the deltoid. Patients who had a modified
      Tikhoff-Linberg resection were able to achieve 10 degrees to 15 degrees greater
      shoulder motion in each direction than were patients who had the classic
      procedure including complete scapulectomy. However, elbow flexion and extension
      strength and forearm pronation strength were greater for the patients with the
      classic resection. Osteoarticular allografts as a reconstructive alternative
      provide as a group the best shoulder motion and overall distal upper extremity
      strength, but these reconstructions were performed only when the rotator cuff
      muscles and deltoid were able to be reconstructed. Diminishing elbow strength was
      seen with longer followup in the patients with osteoarticular reconstructions,
      corresponding temporally to subchondral collapse observed on radiographs. Range
      of shoulder motion except rotation was just as good for allograft vascularized
      fibular arthrodeses as for the osteoarticular allografts, but strength was
      significantly less with the arthrodeses.

PMID- 9553546
TI  - 100 cemented versus 100 noncemented stems with comparison of 25 matched pairs.
AB  - Two series of 100 consecutive primary total hip arthroplasties, each using a
      single design of noncemented or cemented femoral component (all 28 mm heads),
      were compared. One cemented and two noncemented stems underwent revision for
      aseptic loosening. Of unrevised hips, outcome data statistically favored
      cemented, rather than noncemented, stems. The data for cemented and noncemented
      stems, respectively, were: An excellent to good result in 97% versus 88%; thigh
      pain in 3% versus 40%; subsidence in 0% versus 22%; and endosteal cavitation in
      6% versus 12%. For patients with 25 unrevised matched pairs, selected by gender,
      age, diagnosis, and weight, outcome data also statistically favored cemented over
      noncemented stems, respectively: an excellent or good result in 25 versus 20
      hips; thigh pain in two versus eight hips; and subsidence in none versus six
      hips. Midterm followup data for these concurrent total hip arthroplasty series of
      a mid 1980s design revealed prevalence of mechanical failure of 1% for cemented
      stems and 4% for noncemented stems. Corroborating matched pair comparison
      neutralized selection bias as a causative factor for these differences. These
      data indicate contemporary cemented femoral stem fixation is superior to second
      generation noncemented femoral stem fixation. Controlled comparative studies at
      midterm to long term followup, such as in this report, are needed to define
      outcome and indications for current third generation noncemented stem fixation.

PMID- 9553547
TI  - Results of total hip arthroplasty for Crowe Type III developmental hip dysplasia.
AB  - From 1969 through 1980, 90 hips in 82 patients had cemented total hip
      arthroplasty for Type III developmental hip dysplasia. Seventy hips were reviewed
      at an average of 16.6 years (range, 5-23 years) after operation. Aseptic
      loosening developed in 53% of acetabular cups and 40% of femoral stems. Despite
      attempts to place acetabular components in the anatomic center, 18 cups (25.7%)
      were placed outside that area. Using a measurement method to determine the true
      acetabular region and approximate femoral head center, final acetabular loosening
      strongly correlated with initial cup placement. Loosening occurred in 15 of 18
      cups (83.3%) initially positioned outside of the true acetabular region compared
      with loosening in 22 of 52 cups (42.3%) initially positioned within the true
      acetabular region. Acetabular loosening also correlated with initial lateral
      displacement or initial superior displacement of the hip center from the
      approximate femoral head center. Initial cup placement medial to the approximate
      femoral head center was predictive of successful long term acetabular component
      fixation. The method of acetabular reconstruction did not affect eventual cup
      loosening. Placement of the hip arthroplasty center of rotation in or near the
      true acetabular region is recommended.

PMID- 9553548
TI  - 4- to 10-year results with the anatomic modular total knee.
AB  - The outcome of 186 consecutive total knee arthroplasties performed with the
      Anatomic Modular Knee is reported. One hundred forty-two knees had followup of 4
      to 10 years (mean, 6.9 years). Two knees required revision of all components, one
      because of infection and the other for instability. Seven patients underwent
      exchange of the modular tibial polyethylene insert at an average of 84 months
      postoperatively. The mean age of these seven patients at primary arthroplasty was
      54 years. No implant showed clinical or radiographic evidence of loosening and
      there were no complications related to patellofemoral articulation. The revision
      rate of the femoral, tibial, and patellar components was two of 142 or 1.4%. The
      revision rate including exchange of the polyethylene insert was nine of 142 or
      6.3%. This minimally constrained posterior cruciate retaining modular design
      performed well at intermediate followup. The absence of patellofemoral
      complications and aseptic loosening was notable. Wear related phenomena were the
      most common indications for reoperation and these occurred in younger, active
      individuals with relatively thin polyethylene bearings. The relative value of
      modular tibial inserts and the outcome of isolated polyethylene exchanges warrant
      additional study.

PMID- 9553550
TI  - Posterior medial meniscus-femoral insertion into the anterior cruciate ligament.
      A case report.
AB  - Medial meniscal anomalies are rare. The anterior horn insertion into the anterior
      cruciate ligament is the most common. In the course of an arthroscopy for torn
      lateral meniscus, an anomalous band in continuity with the posterior horn of the
      medial meniscus was observed to insert into the anterior cruciate ligament.
      Although the tibial portion of the anterior cruciate was redundant, the anomalous
      band provided tension to the anterior cruciate ligament and a negative pivot
      shift. A previously unreported posterior medial meniscal femoral insertion is
      described.

PMID- 9553549
TI  - Functional gait adaptations in patients with anterior cruciate ligament
      deficiency over time.
AB  - Functional adaptations in knee kinematics and kinetics during level walking in 30
      patients with unilateral anterior cruciate ligament deficiency and 30 healthy
      control subjects were studied. To examine the impact of time after injury on the
      functional adaptations, patients were placed into three time interval groups:
      early, intermediate, and chronic. The patients with anterior cruciate ligament
      deficiency had significantly decreased external knee flexion moments (balanced by
      net quadriceps contraction) and significantly increased external knee extension
      moments (balanced by net knee flexors contraction) as compared with the control
      subjects. As time after the injury increased, changes in the sagittal plane knee
      moments were more pronounced. A significant linear relationship (positive
      correlation) was found between the midstance knee flexion moment and the
      corresponding knee flexion angle. The patients with anterior cruciate deficiency
      had a greater knee flexion angle when generating a comparable midstance knee
      flexion moment as compared to the control subjects. The identification of gait
      adaptations over time provides additional information on the natural history of
      anterior cruciate ligament deficiency and may have implications regarding
      conservative rehabilitation, evaluation of outcomes, progression of meniscal
      injury, and the development of degenerative arthritis of the knee.

PMID- 9553551
TI  - Thromboembolism after foot and ankle surgery. A multicenter study.
AB  - Thromboembolic disease presents a potentially fatal complication to patients
      undergoing orthopaedic surgery. Although the incidence after hip and knee surgery
      has been studied and documented, its incidence after surgery of the foot and
      ankle is unknown. For this reason, a prospective multicenter study was undertaken
      to identify patients with clinically evident thromboembolic disease to evaluate
      potential risk factors. Two thousand seven hundred thirty-three patients were
      evaluated for preoperative risk factors and postoperative thromboembolic events.
      There were six clinically significant thromboembolic events, including four
      nonfatal pulmonary emboli, after foot and ankle surgery. The incidence of deep
      vein thrombosis was six of 2733 (0.22%) and that of nonfatal pulmonary emboli was
      four of 2733 (0.15%). Factors found to correlate with an increased incidence of
      deep vein thrombosis were nonweightbearing status and immobilization after
      surgery. On the basis of these results, routine prophylaxis for thromboembolic
      disease after foot and ankle surgery probably is not warranted.

PMID- 9553552
TI  - Complications in the use of the Bailey-Dubow extensible nail.
AB  - The results of 40 extensible intramedullary nailing procedures in 15 children who
      had osteogenesis imperfecta were reviewed to identify risk factors leading to
      complications of this method of treatment. There were 40 complications, 17 major
      and 23 minor. The 17 major complications led to 15 additional procedures, 10 of
      which were to remove or replace the implant. The prevalence of major
      complications was highest in patients who were younger than 5 years when the nail
      was inserted. Nails placed in the tibia tended to produce a higher incidence of
      major complications than did those placed in the femur, but this difference was
      not statistically significant. By survivorship analysis, patients had a greater
      risk of requiring a revision procedure when a technical error occurred at the
      time the nail was inserted. Patients who had nails placed in the femur tended to
      have a lower risk of needing revision surgery than did those who had nails placed
      in the tibia, but this difference was not statistically significant. The results
      suggested that the extensible nail is most advantageous in the femur and in
      patients older than 5 years. Avoiding technical errors when inserting the nail
      may improve the longevity of the device.

PMID- 9553553
TI  - Osteosarcoma of the pelvis. Oncologic results of 40 patients.
AB  - The cases of 40 patients with osteosarcoma of the pelvis treated between 1977 and
      1994 were reviewed. The location of the tumor was ilium in 30 patients, ischium
      in four, pubis in one, and sacrum in five. Most (58%) of the tumors were of the
      chondroblastic subtype. Thirty patients had surgical excision of the tumors: 10
      with hemipelvectomies and 20 with limb sparing procedures. A wide margin was
      achieved in 16 of 30 (53%) patients, including 12 of 14 who had no sacral tumor
      involvement. Positive margins occurred at the sacrum in 11 patients, lumbar
      vertebra in one, perirectal space in one, and contralateral pubic body in one.
      Macroscopic tumor emboli within the regional large vessels were found in seven
      patients. The incidence of local recurrence was 32%: 13% in wide excisions, 38%
      in marginal excisions, and 80% in intralesional excisions. The 1- and 5-year
      overall patient survivals were 73% and 34%, respectively. Patients who had a
      surgical excision of the primary tumor had a significantly better survival than
      did those treated without surgery (5-year survival; 41% and 10%, respectively).
      Tumor size, surgical excision of the primary tumor, surgical margin, and type of
      surgical procedure were the prognostic factors for patients with Stage IIB
      tumors.

PMID- 9553554
TI  - Polyarticular pigmented villonodular synovitis in a child.
AB  - Pigmented villonodular synovitis is rare in the younger child. Polyarticular
      involvement in this condition, regardless of patient age, is distinctly uncommon.
      The authors describe a case of pigmented villonodular synovitis involving
      multiple joints in a young boy who also had congenital anomalies of the
      genitourinary tract. Although rare, pigmented villonodular synovitis should be
      considered in the differential diagnosis of multiple joint swellings in children
      with congenital anomalies.

PMID- 9553555
TI  - Limb threatening neuropathic complications from ankle fractures in patients with
      diabetes.
AB  - Although less common than neuropathic (Charcot) deformities in feet, ankle
      deformities can occur and produce significant limb threatening complications
      after injury in patients with longstanding diabetes. A series of six such
      complications, including one that resulted in amputation and several near
      amputations, are presented. The authors' primary purpose is to alert or remind
      physicians and orthopaedic surgeons of the often unanticipated but significant
      complications of these rare and seemingly mild ankle injuries. A secondary
      purpose is to point out that complications may be avoided or mitigated with early
      stabilization and possibly with treatment of bone resorbing, inflammatory
      processes characteristic of neuroarthropathies.

PMID- 9553556
TI  - Function of stiff joints may be restored by Ilizarov joint distraction.
AB  - Three patients with joint stiffness caused by trauma or infection are reported.
      The involved joints are the interphalangeal joint of the thumb, patellofemoral
      joint, and ankle joint. As an alternative for the indicated arthrodesis in these
      patients, treatment with articulating joint distraction was performed. By use of
      adapted Ilizarov external ring fixators, gradual distraction was applied to
      loosen the joint, followed after loosening by a period of exercise during
      distraction. In all three patients this experimental approach led to a decrease
      in pain and improvement of joint function that persisted for at least 2 years
      after treatment. With the use of Ilizarov joint distraction, joint function in
      cases of joint stiffness may be restored, and the need for an arthrodesis can be
      postponed.

PMID- 9553557
TI  - Telemedicine and orthopaedic care. A review of 2 years of experience.
AB  - The objective of this study was to study the delivery of orthopaedic care via a
      telemedicine network. This study is a descriptive analysis of orthopaedic
      teleconsultations done during a 2-year period by three orthopaedic surgeons. Four
      hundred ten teleconsultations were done during the study period from February 1,
      1995, to December 31, 1996. Orthopaedic surgeons engaged in 91 teleconsultations
      (22% of all teleconsultations). Reasons for orthopaedic teleconsultations were:
      evaluation and treatment of fracture care (39 cases; 43%); evaluation and
      treatment of ligamentous injury, joint swelling and infection (32 cases; 35%);
      postoperative evaluation (16 cases; 18%); and evaluation and treatment of
      dislocations (four cases; 4%). Sixty-two (68%) of the patients remained in the
      rural community. Twenty-one (23%) of the orthopaedic teleconsultations were
      classified as emergent (done immediately). Thirty-five (38%) were urgent (done
      within 1 to 2 hours of provider request), and 35 (38%) were scheduled. The mean
      duration of time for teleconsultations was 12.8 minutes. Eighty-seven (96%) of
      the teleconsultations occurred Monday through Friday. Outcome data were collected
      on all patients involved in teleconsultations. No adverse patient outcomes
      occurred. This study suggests telemedicine may be an avenue for the delivery of
      orthopaedic care to patients residing in areas where orthopaedic specialists are
      not available.

PMID- 9553558
TI  - Tibiofemoral contact pressures in degenerative joint disease.
AB  - Using tibiofemoral joints from older (age, 53-80 years) human cadavers with
      articular cartilage degeneration, contact pressures and contact areas were
      measured in the extended knee in four conditions: (1) neutral alignment; (2) 5
      degrees varus (simulating single limb stance of gait); (3) 5 degrees valgus; and
      (4) after a 5 degrees proximal tibial closing wedge valgus osteotomy. In
      degenerated cartilage, contact pressures were reduced at the lesion sites and
      were high on the borders of the lesions. No statistically significant changes
      occurred in contact pressures and areas when values from neutral loading were
      compared with values during loading in each of the other three conditions.
      Lateral average and maximum contact pressures were less in varus loading than in
      valgus loading. Equal medial and lateral contact pressures during varus loading,
      in contrast to lower medial than lateral contact pressures in the other three
      loading, supports the theory that the varus moment imposed on the knee in single
      limb stance could be a mechanism causing medial tibiofemoral osteoarthritis. The
      5 degrees valgus osteotomy resulted in contact pressures similar to those in
      neutral loading. These experiments do not support the value of the 5 degrees
      valgus osteotomy in reducing contact pressures on the medial tibial plateau.

PMID- 9553559
TI  - Healing of the anterior attachment of the rabbit meniscus to bone.
AB  - In a rabbit model the healing process of the anterior attachment of the medical
      meniscus was observed during the first 12 weeks after sharp transection and
      refixation in a tibial bone channel. Evaluations of the healing tissue were
      histologic analysis, application of immunohistochemical methods to show collagen
      types and nerve regeneration, and mechanical load to failure tests. Secondary
      changes to knee joint cartilage, as signs of eventual dysfunction of the refixed
      meniscus, were evaluated by analysis of proteoglycan fragment concentration in
      joint fluid and histologic analysis of knee joint articular cartilage and
      synovium. The healing tissue between the refixed attachment and bone matured from
      highly cellular, nonspecific granulation tissue at 1 week, to bone,
      fibrocartilaginous, and fibrous tissues, which at some sites developed an
      insertion specific tissue arrangement within a 12-week period. However, the
      irregular interface between the fibrocartilaginous tissue and the underlying
      bone, which is typical for a normal insertion, was not reestablished. Labeling
      for collagen Types I and II in the newly formed insertion did not return to
      normal. In addition a few collagen fibers connected the refixed attachment tissue
      to bone. New bone formation turned the initially cancellous bone tunnel walls
      into more solid cortical bone. However, new bone formation did not fill the
      distal part of the channel. The refixed meniscal attachment underwent necrosis
      and was revitalized by cell ingrowth from the periphery. Nerve fibers were found
      in the newly formed insertion by 12 weeks. The failure load at tensile testing
      never reached more than 20% that of a normal attachment. Degeneration of
      articular cartilage and increased proteoglycan fragment in the joint fluid were
      common after this procedure. These data suggest that, despite the focal
      appearance of insertion specific tissues and healing of collagen fibers to bone,
      the tissue architecture of a normal meniscal insertion and a normal meniscal
      joint protective function were not reestablished.

PMID- 9553560
TI  - Osteogenesis of electrically stimulated bone cells mediated in part by calcium
      ions.
AB  - Culture selected and expanded osteoblastic cells may be able to be reintroduced
      into massive skeletal defects to accelerate cell mediated regeneration of
      skeletal tissues, especially in bone ingrowth in total joint replacement,
      fracture healing, and osteoporosis. In vitro osteogenic cell culture is a useful
      model in studying the mechanism of bone metabolism under direct current
      stimulation. In this study, an osteoblastlike cell line was isolated from newborn
      rat calvaria. The osteogenic processes of the in vitro cultured cell line were
      studied by cytochemical, electron microscopic, and energy dispersive x-ray
      analysis techniques that resembled those observed in membrane bone ossification
      centers in vivo. Direct current stimulation of 100 microA/cm2 accelerated greatly
      the proliferation and calcification of the in vitro cultured cells. Intracellular
      free calcium ion metabolism was measured with an Adherent Cell Analysis and
      Sorting Machine. Under direct current stimulation, intracellular free calcium ion
      concentration increased an average of 2.3 times of the original level, which may
      play a key role in regulating osteogenesis and bone metabolism.

PMID- 9553561
TI  - Biomechanical topography of human articular cartilage in the first
      metatarsophalangeal joint.
AB  - The objective of this study was to provide a map of cartilage biomechanical
      properties, thickness, and histomorphometric characteristics in the human,
      cadaveric first metatarsophangeal joint, to determine if normal articular
      cartilage was predisposed topographically to biomechanical mismatches in
      articulating surfaces. Cartilage intrinsic material properties and thickness were
      obtained from seven pairs of human, freshly frozen, cadaveric,
      metatarsophalangeal joints using an automated creep indentation apparatus under
      conditions of biphasic creep. Eight sites were tested: four on the metatarsal
      head, two on the proximal phalanx base, and one on each sesamoid bone to obtain
      the aggregate modulus, Poisson's ratio, permeability, shear modulus, and
      thickness. Cartilage in the lateral phalanx site of the left metatarsal head had
      the largest aggregate modulus (1.34 MPa), whereas the softest tissue was found in
      the right medial sesamoid (0.63 MPa). The medial phalanx region of the right
      joint was the most permeable (4.56 x 10(-15) meter4/Newton-second), whereas the
      medial sesamoid articulation of the metatarsal head of the left joint was the
      least permeable (1.26 x 10(-15) meter4/Newton-second). Material properties and
      thickness are indicative of the tissue's functional environment. The lack of
      mismatches in cartilage biomechanical properties of the articulating surfaces
      found in this study may be supportive of clinical observations that early
      degenerative changes, in the absence of traumatic events, do not occur at the
      selected test sites in the human first metatarsophalangeal joint.

PMID- 9553562
TI  - Ankle pain and swelling in a 10-year-old girl.

PMID- 9553563
TI  - Pathogenesis of bone loss after total hip arthroplasty.
AB  - Bone loss with or without evidence of aseptic loosening is a long term
      complication after total hip arthroplasty (THA). It occurs with all materials and
      in all prosthetic systems in use or that have been used to date. Bone loss after
      THA can be a serious problem in revision surgery because bone deficiencies may
      limit reconstructive options, increase the difficulty of surgery, and necessitate
      autogenous or allogenic bone grafting. There are three factors adversely
      affecting maintenance of bone mass after THA: (1) bone loss secondary to
      particulate debris; (2) adaptive bone remodeling and stress shielding secondary
      to size, material properties, and surface characteristics of contemporary
      prostheses; and (3) bone loss as a consequence of natural aging. This chapter
      reviews the mechanisms of the primary causes of bone loss after THA.

PMID- 9553564
TI  - The pathogenesis of bone loss following total knee arthroplasty.
AB  - Bone loss following total knee arthroplasty (TKA) may be focal or diffuse. It may
      be caused mechanically, either by unloading of the bone leading to disuse
      osteoporosis, or by overloading of the bone leading to trabecular fractures and
      bone destruction. Osteolysis, instigated by an inflammatory reaction to
      particulate wear debris, is an important and common cause of bone loss after TKA.
      Less common, though sometimes dramatic, causes of bone loss are infection and
      osteonecrosis.

PMID- 9553565
TI  - Biology of allografting.
AB  - Allograft bone continues to play an important role in revision hip and knee
      arthroplasty. A basic understanding of allograft biology and immunology is
      important in order to increase the success of allografting. Although the
      literature has a wealth of knowledge on the subject there are still many
      unknowns. The role of immunology in bone transplantation has been known for a
      long time, but only recently has it become apparent that the bone remodeling
      system and the immunologic system interact to affect the clinical success of bone
      transplantation. Neither of these two systems are completely understood nor is
      their interaction. Future research in the field of bone transplantation will be
      aimed at a better understanding of these systems individually but, more
      important, how they interact in humans. Until that time, allografting still can
      be used with success if one understands the role of allograft biology,
      immunology, and the important role of the host environment in bone
      transplantation.

PMID- 9553566
TI  - Classification and preoperative radiographic evaluation: knee.
AB  - Preoperative radiographic planning for revision total knee arthroplasty begins
      with obtaining excellent quality AP and lateral radiographs that permit: 1.
      Evaluation of the extent of bone loss in the metaphyseal region of the femur and
      tibia. 2. Full visualization of the patient's intramedullary canal for
      determining appropriate stem size and length. The surgeon should then determine
      the appropriate bone defect classification, keeping in mind the provisions needed
      to address Type 2 and 3 defects. These provisions include any augments or
      allografts, stemmed components, and the degree of component constraint needed in
      the patient's revision surgery. Through preoperative templating, the surgeon can
      determine whether a particular implant system provides the options necessary to
      achieve an optimal surgical result. Whenever templating leaves unanswered
      questions regarding the extent of bone damage or the degree of knee instability,
      the surgeon must prepare for the worst case scenario to ensure that the
      appropriate components and graft material are made available.

PMID- 9553567
TI  - The classification and radiographic evaluation of bone loss in revision hip
      arthroplasty.
AB  - Many classification systems have been described over the past 10 years for bone
      loss that is found in association with the failed hip arthroplasty. Most are
      based on assessments of bone stock that are made intraoperatively. Good-quality
      plain radiography is the most useful preoperative investigation and provides
      important information regarding the residual bone stock. There is a need for
      critical appraisal of the validity of classification systems currently in use and
      the development of a consensus system that will permit comparison between the
      published results of different techniques.

PMID- 9553568
TI  - Seven specialized exposures for revision hip and knee replacement.
AB  - With the increasing rates and complexity of revision hip and knee arthroplasty,
      it has become more important than ever to approach the joint in a safe and
      rational manner. The development of extensile approaches have significantly
      simplified the removal of solidly fixed components without compromising bone
      stock. The extended trochanteric osteotomy enables controlled access to the
      femoral component and is a useful technique for revision of solidly-fixed femoral
      components. The trochanteric slide allows comprehensive exposure of the
      acetabulum and femur comparable to trochanteric osteotomy with a diminished risk
      of trochanteric escape. The vastus slide allows wide exposure of the femoral
      shaft when using an anterolateral approach. In revision total knee arthroplasty,
      the extensor mechanism is often at risk of disruption or avulsion, and in most
      cases, maneuvers that allow wide exposure of the femur and tibia while preserving
      the extensor mechanism are essential. Such exposures include one of the extensor
      mechanism reflecting techniques either proximally by rectus snip or patellar
      turndown, or distally by tibial tubercle osteotomy. Occasionally a femoral peel
      or epicondylar osteotomy is required. There should be a low threshold to consider
      one of these specialized approaches during revision hip and knee arthroplasty.

PMID- 9553569
TI  - Role and results of the high hip center.
AB  - Anatomic placement of the acetabular component should be the surgeon's goal at
      the time of revision THA. However, Acetabular loosening with subsequent implant
      migration, progressive superior acetabular bone destruction or severe pelvic
      osteolysis, may prevent the surgeon from obtaining adequate host bone-implant
      contact needed for a successful reconstruction while maintaining a normal hip
      center. The high hip center offers a technique for reconstruction of an
      acetabulum with severe bony deficiency and where the majority of the remaining
      host bone is superior to the anatomic hip centre.

PMID- 9553570
TI  - Jumbo cups and morsalized graft.
AB  - Revision of failed acetabular components presents a formidable problem due to
      associated loss of bone and sclerosis of the remaining bone. Uncemented
      acetabular components with porous surfaces have revolutionized acetabular
      revision surgery. They can be stabilized into the existing host bone with
      supplemental screws even in the face of major bone loss. Nonstructural
      particulate bone grafts can then be used to supplement the bone stock. With large
      defects, jumbo acetabular components ranging in sizes from 70 to 80 millimeter
      outer diameters can be stabilized on the acetabular rim while the defects can be
      grafted with morsalized bone. Nineteen of such revisions performed for major bone
      loss without pelvic discontinuity between February 1986 and December 1988 were
      evaluated at a mean follow-up period of ten years (range eight to eleven years).
      One component had been revised for sepsis. None of the others had been revised.
      Definite radiographic failure of fixation of the acetabular component was not
      seen on any of the other hips. These results strongly support the use of jumbo
      uncemented acetabular components with morsalized bone grafts even in the face of
      major acetabular bone loss.

PMID- 9553571
TI  - Reconstruction rings and bone graft in total hip revision surgery.
AB  - This article deals with the design and indications of use of reconstruction rings
      and cages plus bone graft for acetabular revision. Details of the technique and
      the available results are presented and the advantages and disadvantages of
      current designs are discussed.

PMID- 9553572
TI  - Role and results of segmental allografts for acetabular segmental bone
      deficiency.
AB  - Acetabular reconstruction in both primary and revision hip arthroplasty often
      requires reconstruction of deficient acetabular bone stock. The exact role of
      allografts remains controversial. Published results of structural allografting
      are presented. Recent literature supports the use of segmental allografts for
      reconstruction of large segmental and combined defects.

PMID- 9553573
TI  - Modified cups.
AB  - Late results of structural allografting of the acetabulum are quite variable. In
      order to reduce or avoid the necessity for bone grafting, some modified cups have
      been developed. The deep cup with or without a lateralized polyethylene liner
      reduces the problem of the protrusio socket. Oblong or bilobed ingrowth cups
      significantly reduce the need for grafting of the roof-deficient acetabulum.
      Constrained or capture polyethylene liners are useful in the unstable hip.

PMID- 9553574
TI  - Impaction allografting with cement for the management of femoral bone loss.
AB  - Impaction allografting with cement is the only technique currently available
      which reverses the diminution of bone stock that occurs in a revision hip
      arthroplasty, and as such, has great potential. It is particularly appropriate in
      the younger patient, though older patients may also benefit from the technique.
      Although the short term results are encouraging, there is a need for further
      basic science research to determine the optimal graft material and prosthesis
      design. Refinements in surgical instrumentation and technique will continue to
      improve the predictability of the clinical result and expand the indications for
      this important addition to the available options in revision hip arthroplasty.

PMID- 9553575
TI  - Onlay cortical allografting for the femur.
AB  - Failed femoral total hip replacement components are frequently associated with
      bone loss. At the time of revision surgery, the goals are to create a construct
      that relieves pain, is stable, and preserves and enhances bone stock. This
      article discusses Materials and Methods, Indications, Operative Technique, and
      Results regarding onlay cortical allografting for the femur.

PMID- 9553576
TI  - Proximal femoral allografts for reconstruction of bone stock in revision
      arthroplasty of the hip.
AB  - Full circumferential bone loss of the proximal femur can be managed by segmental
      allografts. The use of these grafts is indicated for uncontained defects longer
      than five cm in length. The femoral implant is cemented into the allograft but
      not into the host. The allograft host junction is stabilized by a step cut or
      oblique osteotomy and autografted with residual host femur. The results at five
      and nine years support this kind of reconstruction as a good alternative for this
      difficult problem.

PMID- 9553578
TI  - Principles of revision total knee arthroplasty.
AB  - Revision total knee replacement is a demanding surgical exercise that requires
      close adherence to a number of guiding principles if clinical results are to be
      maximized and complications avoided. To achieve consistently good results in
      revision total knee replacement, considerable emphasis has to be placed on
      preoperative planning, surgical exposure, dealing with bone defects, and
      selecting a proper revision implant.

PMID- 9553577
TI  - Bypass fixation.
AB  - Hip replacement has been a great achievement of orthopaedic surgery as it
      reliably abolishes pain and restores function. The success of this operation has
      lead to its use not only in the elderly, but increasingly, in the higher demand
      that younger patients whose life expectancy is longer than the longevity of the
      prostheses used to date. Thus, we are seeing a growing number of patients who
      require a first or even repeat revision surgery, which is often complex and
      technically demanding.

PMID- 9553579
TI  - The role and results of bone grafting in revision total knee replacement.
AB  - Failure in total knee replacement requiring revision surgery is often accompanied
      by significant bone loss and soft tissue asymmetry. When embarking on these
      complex reconstructions, careful preoperative planning is necessary to ensure
      that these deficiencies will be corrected by surgical technique and implant
      selection. This article discusses various techniques and results of bone grafting
      in revision total knee arthroplasty.

PMID- 9553580
TI  - Modular augments in revision total knee arthroplasty.
AB  - Modularity in total knee arthroplasty is extremely helpful in the management of
      patients with complex primary and revision total knee arthroplasties. Modularity
      allows selective augmentation to deal with bone deficiencies on the distal and
      posterior femur. The ability to selectively augment the femur is very helpful in
      balancing the soft tissues and providing stability. Selective augmentation of the
      femur allows restoration of the joint line and more normal patellar and
      collateral ligament kinematics. Selective modular augments on the tibia allow
      dealing with bone deficiency without the concerns of bone graft incorporation.
      Modular extended intramedullary stems allow the option of either press-fit or
      cement fixation of the stem, entailing the stem diameter length to the given
      patient.

PMID- 9553581
TI  - Management of the patella during revision total knee replacement arthroplasty.
AB  - Managing the patella and balancing the patellofemoral joint space is one of the
      most difficult aspects of performing a primary total knee replacement (TKR). The
      situation is compounded in the revision situation. Unfortunately, an otherwise
      well-performed TKR will fail because of problems with the patella or the extensor
      mechanism. This article discusses various aspects of the management of the
      patella and extensor mechanism during revision TKR with an objective of
      minimizing complications and maximizing functional outcomes. The topics covered
      include exposure of the patella and extensor mechanism during revision surgery,
      whether or not to remove all prior patellar implants, the technique for removal
      of a prior implant, the management of bone loss or fractures of the patella
      during revision TKR, the insertion (or noninsertion) and fixation of a new
      implant, and the balance of the patellofemoral joint space, including avoidance
      of patella baja or patella alta. A compilation of scientific and "no-so"
      scientific data and experience gleaned over the past 26 years of total knee
      replacement surgery will be presented.

PMID- 9553583
TI  - Medicine following the HCFA 'guidelines'.

PMID- 9553582
TI  - Results of revision total knee arthroplasty in the face of significant bone
      deficiency.
AB  - The successful approach to the failed knee with bone deficiency is dependent upon
      thorough planning prior to surgery in order to have the resources available in
      terms of adequate bone allograft and suitable revision implants. The approximate
      size of bone stock deficiency can be calculated from preoperative radiographs and
      similarly ligamentous incompetence can often be diagnosed clinically prior to
      surgery. Smaller defects of up to 1 to 1.5 cm in depth and localized in the main
      to a single side of the tibial plateau or to a single femoral condyle can be
      dealt with using smaller grafts that may be local autograft or allograft, or
      modular wedges. Larger tibial defects can be compensated for using conventional
      revision systems by thicker polyethylene and augmented baseplates, but once the
      flexion-extension gap reaches approximately 40 mm this is no longer possible and
      structural graft or customized componentry becomes necessary. Femoral defects
      larger than about 1 cm that cannot be made up by augments necessitate grafting.
      The need to use a large proximal tibial allograft also may dictate the operative
      approach used to expose the joint, especially in the situation of a multiply
      operated tight knee. In such cases the use of a quadriceps turndown may be more
      advisable than the use of a tibial tubercle osteotomy as the osteotomy may well
      not have an adequate bed to heal to following the reconstruction. Several series
      have reported cases of patellar tendon avulsion and the clinical results
      following this complication usually are not satisfactory. Preoperatively it is
      important to identify, if possible, the case that is likely to require a more
      extended approach because of a tight soft tissue envelope. The reports of results
      of series of revision total knee arthroplasty in the setting of significant bone
      loss are at present confined to short-term followup. The clinical results of
      these series are satisfactory at this early point in time, but decision regarding
      the durability of reconstructions requiring major structural allografting awaits
      longer-term study. Of concern is the devastating complication of infection
      following such revision surgery, the risk of which is amplified in the setting of
      prior infection. In addition, the long-term viability of major structural grafts
      in the setting of loading is uncertain as the risk of graft collapse in the
      process of incorporation is not known. Notwithstanding these concerns, major
      grafting is sometimes the only recourse to achieve satisfactory revision of a
      failed arthroplasty. The use of such major grafts is therefore cautiously
      supported and because of the risks inherent in such surgery we believe that such
      surgery should be carried out in the setting of specialist interest units.

PMID- 9553584
TI  - Cardiac arrhythmias set to music.

PMID- 9553585
TI  - Which antibiotics for acute sinusitis?

PMID- 9553586
TI  - What can I do for you today?

PMID- 9553587
TI  - Detecting osteoporosis. Beyond the history and physical examination.
AB  - A number of developments are contributing to clinicians' understanding of
      osteoporosis as a clinical continuum characterized by low bone mass and increased
      risk of fractures rather than as a disease characterized by fragility fractures.
      With improved capability for accurate measurement of bone mass, the prevalence of
      this disease has increased to include at least 25 million Americans. The
      responsibility of primary care physicians to detect and treat osteoporosis has
      increased accordingly. Parents should be counseled regarding their children's
      diet and lifestyle to optimize peak adult bone mass and ensure adequate dietary
      calcium intake. Adults should be counseled to minimize behaviors that result in
      accelerated bone loss (e.g., smoking, alcohol use, anorexia, bulimia). Physicians
      need to be aware of the serious potential complications of osteoporosis and offer
      counseling to menopausal women about the disease and the benefits and risks of
      hormone replacement and estrogen replacement therapy. Physicians should be
      familiar with technologies available in their community for measuring bone mass
      and recognize the need to consider prescribing pharmacologic and nonpharmacologic
      therapies for patients with low bone mass or osteoporosis. Physicians also can
      educate caregivers about prevention of falls and fractures in elderly patients
      who are unsteady on their feet. Improved technologies for bone mass measurement
      and fracture risk assessment, as well as expanded options for treatment and
      prevention of osteoporosis, are likely to become available within the next 5 to
      10 years, thereby increasing the wisdom of early detection and treatment of
      osteoporosis.

PMID- 9553588
TI  - Conservative management of lumbar spinal stenosis. Identifying patients likely to
      do well without surgery.
AB  - Lumbar spinal stenosis is a painful condition that often leads to irreversible
      neurologic damage and functional disability. Thus, early diagnosis and management
      are important. Conservative therapy, which is appropriate for many patients,
      minimizes invasive intervention and decreases the risks of morbidity. As more
      people live to older ages, the incidence of lumbar spinal stenosis will likely
      increase. If results of a thorough history and physical examination suggest the
      disorder, a course of appropriate physical therapy should be started promptly;
      more expensive tests and treatments are reserved for patients whose pain is
      refractory to early conservative intervention. However, if pain is severe, if the
      origin is not clear, or if neurologic deficits quickly become worse, immediate
      neuroradiologic studies should be considered, including timely EMG. Strong
      guidance by the primary care physician is of paramount importance because the
      therapeutic program is lengthy. Additional help from a physiatrist, neurologist,
      or orthopedic surgeon may be indicated as treatment progresses.

PMID- 9553589
TI  - Juvenile psoriasis. Early interventions can reduce risks for problems later.
AB  - Psoriasis is a lifelong disease with genetic, systemic, and environmental roots
      and an unpredictable course. In more than one third of patients, onset is in the
      first two decades of life. Primary care physicians are in a unique position to
      help these young patients by providing early treatment and education.

PMID- 9553590
TI  - The blurred vision mystery. Idiopathic intracranial hypertension.

PMID- 9553592
TI  - Management of COPD. Early identification and active intervention are crucial.
AB  - Medical management of COPD begins with an awareness of risk factors and
      identification of at-risk patients. Once disease is identified, patient and
      family education, a smoking cessation program, and an appropriate bronchodilator
      regimen should be initiated. Airway secretions and infections should be
      minimized, hypoxemia corrected, and other secondary physiologic disturbances
      evaluated when appropriate. Participation in a comprehensive pulmonary
      rehabilitation program can markedly improve symptoms, function, exercise
      performance, and quality of life. The results are a reduction in patient
      limitations, medical expenses, and dependence on medical facilities and
      caregivers.

PMID- 9553591
TI  - Diagnosing chronic obstructive pulmonary disease. The importance of
      differentiating asthma, emphysema, and chronic bronchitis.
AB  - In patients with chronic obstructive pulmonary disease (COPD), a thorough
      understanding on the clinician's part of the pathophysiologic basis of airflow
      limitation greatly enhances decisions regarding care. Differences in prognosis
      among the major types of COPD have become clear, and identification of airway
      inflammation has dramatically altered medical therapy. Dr Martinez, who
      coordinated this symposium, here explains the importance of judiciously applying
      findings from history taking, physical examination, laboratory studies
      (particularly pulmonary function testing), and radiographic studies to all
      aspects of disease management. The remaining four symposium articles address
      specific avenues for treatment of emphysema and chronic bronchitis.

PMID- 9553593
TI  - Long-term oxygen therapy for COPD. Improving longevity and quality of life in
      hypoxemic patients.
AB  - Long-term oxygen therapy can increase life expectancy in hypoxemic patients with
      COPD. Accurate identification of hypoxemia requires arterial blood gas
      measurements. Pulse oximetry can be used to measure trends in oxygenation, oxygen
      needs, and oxygen requirements during exercise and sleep. A detailed oxygen
      prescription indicates: (1) the oxygen dose (L/min), (2) the number of hours per
      day that oxygen therapy is required, (3) the dose required during exercise, (4)
      the oxygen supply system: concentrator, compressed gas cylinder, or liquid oxygen
      reservoir, and (5) the delivery device: nasal cannula, demand-flow device,
      reservoir cannula, or transtracheal oxygen catheter.

PMID- 9553594
TI  - Pulmonary rehabilitation for COPD. A practical approach for improving ventilatory
      conditioning.
AB  - Pulmonary rehabilitation has gradually become the "gold standard" for patients
      with severe lung disease, especially chronic obstructive pulmonary disease
      (COPD). Because some newer therapeutic strategies, such as lung volume reduction
      surgery and lung transplantation, require well-conditioned patients, pulmonary
      rehabilitation is now considered essential for many patients formerly deemed
      untreatable. In this article, Dr Celli reviews the basic goals, components, and
      benefits of pulmonary rehabilitation for COPD and other chronic respiratory
      diseases.

PMID- 9553595
TI  - Surgery for severe COPD. Lung volume reduction and lung transplantation.
AB  - A management strategy for patients with severe emphysema is shown in figure 2 on
      page 199. Although the reported physiologic improvements after LVRS are
      significantly less than those seen after lung transplantation, LVRS has the
      potential to improve functional performance in a larger number of patients
      because of wider availability. Moreover, it accomplishes these goals without the
      attendant risks associated with transplantation and immunosuppression. The
      efficacy of LVRS over standard medical therapy in influencing survival and
      favorably affecting physiologic variables at rest and during exercise remains to
      be elucidated in NETT. Lung transplantation should be reserved for those patients
      deemed unsuitable or too ill for LVRS. It is to be hoped that future developments
      in organ preservation techniques and immunosuppressive regimens will expand the
      donor pool and decrease the incidence of posttransplantation bronchiolitis.

PMID- 9553596
TI  - Evaluation of bleeding disorders. A detailed history and laboratory tests provide
      clues.
AB  - A single, optimal screening laboratory test for hemostasis would evaluate
      vascular, platelet, coagulation, and fibrinolytic functions. Unfortunately, such
      a test does not exist. The key factor in determining the presence of a bleeding
      diathesis is obtaining a detailed patient history. Results of coagulation tests
      should always be interpreted in the context of such a history. Screening tests
      include platelet count, PTT, and PT. Subsequent investigations depend on the
      results of these tests.

PMID- 9553597
TI  - Intravenous thrombolytic therapy for acute ischemic stroke. Weighing the risks
      and benefits of tissue plasminogen activator.
AB  - The use of intravenous tPA within 3 hours after acute ischemic stroke has been
      proved to increase the number of good outcomes. However, tPA is a toxic therapy
      that carries a substantial risk of intracerebral hemorrhage. To decrease the
      risk, tPA use must be restricted to a carefully selected patient population.
      Treatment must be administered in an intensive care setting and directed by
      physicians with expertise in diagnosing and managing stroke.

PMID- 9553598
TI  - When to worry about spider bites. Inaccurate diagnosis can have serious, even
      fatal, consequences.
AB  - Almost all species of spiders are capable of biting people, but the bites of only
      a few are medically significant. Physicians need to be able to recognize the
      clinical signs and symptoms of common venomous spider bites and administer
      appropriate therapy. This may be difficult, since the offending spider is rarely
      seen or recovered for identification. Knowledge of life cycles, habits, and
      toxicity of venomous spiders enables physicians to provide more comprehensive
      medical care of bite victims. It is hoped that study of immunologic mechanisms
      and inflammation mediators will lead to the development of new treatments.

PMID- 9553599
TI  - Hereditary angioedema. Complex symptoms can make diagnosis difficult.
AB  - Although rare, hereditary angioedema is a potentially life-threatening disorder
      that can be difficult to diagnose. It is characterized by a deficiency in C1
      esterase inhibitor (C1 INH). Manifestations include gastrointestinal,
      subcutaneous, and respiratory edema. Factors that trigger episodes vary. Symptoms
      typically last 48 to 72 hours, but they can last 4 hours to 1 week. Treatment
      includes prophylactic therapy with attenuated androgens or antifibrinolytic
      agents. Acute episodes can be medical emergencies, and airway management is a
      major concern. The treatment of choice in an acute episode is administration of
      plasma concentrate of C1 INH.

PMID- 9553600
TI  - Alcoholic liver disease. Treatment strategies for the potentially reversible
      stages.
AB  - Even modest alcohol ingestion can increase the risk of steatosis, and long-term,
      excessive consumption can lead to alcoholic hepatitis and eventually cirrhosis.
      Most patients with clinically significant alcoholic liver disease have histologic
      findings typical of all three conditions. The only clearly beneficial treatment
      is abstinence from alcohol. Abstinence in combination with proper nutrition and
      general supportive care is state of the art. Steatosis is reversible upon
      withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence
      and may progress to cirrhosis. Corticosteroid therapy may reduce short-term
      mortality rates in patients with moderate or severe alcoholic hepatitis who have
      hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding.
      Treatment with colchicine may decrease the risk of cirrhosis; however, once
      cirrhosis has developed, the liver damage is irreversible. The prognosis is
      improved with abstinence, but complications (e.g., ascites, gastrointestinal
      bleeding) often occur. Liver transplantation may be considered in patients with
      severe complications.

PMID- 9553601
TI  - Identifying and treating urinary incontinence. The crucial role of the primary
      care physician.
AB  - Urinary incontinence is a widespread problem that often goes undiagnosed and
      untreated. Many patients are unwilling to discuss it with their physician because
      of embarrassment or the belief that nothing can be done. Consequently, physicians
      need to routinely inquire about symptoms so incontinent patients can be
      identified. Physicians should reassure patients that urinary incontinence is
      usually a symptom of a correctable problem. Careful evaluation and office tests
      to determine the type and cause of urinary incontinence, together with
      appropriate treatment, often lead to improvement in symptoms or return to
      continence.

PMID- 9553602
TI  - Cumulative indexes for volumes 230-241.

PMID- 9553603
TI  - Alcohol and health.

PMID- 9553604
TI  - Natural progesterone.

PMID- 9553605
TI  - Wasting away: cancer cachexia.

PMID- 9553606
TI  - Echocardiography stress tests.

PMID- 9553607
TI  - Caution for new diet drug.

PMID- 9553609
TI  - Minimizing migraines.

PMID- 9553608
TI  - Genetic testing and Alzheimer's disease.

PMID- 9553610
TI  - Drug therapy for prostate problems.

PMID- 9553611
TI  - Narcolepsy.

PMID- 9553613
TI  - More resistant bugs?

PMID- 9553612
TI  - When to treat thyroid nodules.

PMID- 9553614
TI  - Sunscreen & cancer.

PMID- 9553615
TI  - On the biomechanical properties of the cornea with particular reference to
      refractive surgery.

PMID- 9553616
TI  - Therapeutic management of hematological malignancies in elderly patients.
      Biological and clinical considerations. Part III: The chronic leukemias and
      myelofibrosis.
AB  - The different therapeutic options available for the treatment of chronic
      leukemias and myelofibrosis are discussed. In reference to chronic myeloid
      leukemia (CML), the choice of the most appropriate treatment must take into
      account not only the clinical condition but also the age of the patient. While
      subjects under 50 might benefit from the options offered by alpha-interferon,
      bone marrow and peripheral stem cell transplant, in older age groups treatment of
      the chronic phase must still rely on standard treatment. Chronic lymphocytic
      leukemia (CLL) and its variants is a disease of mostly middle and late life, with
      a variable clinical course. Patients show wide differences in morbidity and
      mortality. Many features have been shown to influence the prognosis, and the most
      important ones are incorporated into the staging systems currently in use. The
      results obtained from the study of large trials support the concept that
      treatment of patients with stable stage A CLL should be postponed until
      progression of disease. Treatment relies principally on alkylating agents,
      corticosteroids and radiation therapy; the new nucleoside analogues, such as
      fludarabine and 2-chlorodeoxyadenosine, have recently acquired established value
      in improving overall survival. With regard to myelofibrosis, the histological and
      biological features that influence the natural course of the disease are
      described, as well as the choice of the most appropriate treatment, which ranges
      from the use of alkylating agents and androgens, to splenectomy and splenic
      irradiation.

PMID- 9553618
TI  - Age- and menopause-related changes in speed of sound and ultrasound attenuation
      of the os calcis in a healthy Italian female population.
AB  - This study assessed changes in ultrasonometric variables of bone (speed of sound,
      broadband ultrasound attenuation and stiffness) related to age and years since
      menopause in a normal Italian female population. Two hundred and thirty-one
      healthy female subjects, age range 18-78 years, divided into two groups (113 pre
      menopausal, age range 18-51 years, and 118 post-menopausal, age range 46-78
      years), were investigated. The results obtained show that there was a linear
      decrease in speed of sound, broadband ultrasound attenuation and stiffness with
      age; a similar pattern was also observed in post-menopausal women as far as the
      correlations between ultrasonometric variables and both age and years since
      menopause were concerned. In particular, speed of sound declined at a rate of
      0.86 m/s for each year post-menopause, while broadband ultrasound attenuation
      declined at 0.4 dB/MHz, and stiffness at 0.5 units. These findings suggest that
      ultrasound variables might be able to detect characteristics of bone that are
      barely influenced by estrogen deficiency, and depend on other factors. Therefore,
      ultrasound measurement should be considered as a possible alternative to x-ray
      densitometry for the assessment of the skeleton.

PMID- 9553617
TI  - Alterations in beta-adrenoceptor mechanisms in the aging heart. Relationship with
      heart failure.
AB  - In chronic heart failure substantial and characteristic changes occur in the
      function of the adrenergic nervous system. Studies in isolated left ventricular
      muscle and in single cardiomyocytes from experimental models of aging and,
      recently, from humans show an age-related reduced contractile response to beta
      adrenoceptor stimulation. "beta-adrenoceptor desensitization" is thought to be a
      general and common mechanism to explain the age- and heart failure-related
      decrease in beta-adrenoceptor response. The aim of this review is to compare
      alterations in beta-adrenoceptor mechanisms in physiological cardiovascular aging
      and chronic heart failure. From an analysis of the overall data on the role of
      aging in beta-adrenoceptor regulation in human and animal hearts, it is possible
      to conclude that the reduced response to beta-agonists is common to all species
      and all cardiac tissues. Moreover, the age-related changes are limited to beta
      adrenoceptor-G-protein (s)-adenylyl cyclase system abnormalities, while the type
      and level of abnormalities change with species and tissues. The modifications
      shown in the aging heart are not very different from some observed in heart
      failure. In particular, both in aged and failing hearts we may see that the
      decrease in beta-adrenoceptor responsiveness is related to changes in G-protein
      function.

PMID- 9553619
TI  - Autonomic nervous activity in elderly dipper and non-dipper patients with
      essential hypertension.
AB  - The pathogenetic mechanisms of the blunted nocturnal fall in blood pressure,
      frequently observed in elderly patients with essential hypertension, are unclear.
      The aim of this study was to evaluate the autonomic nervous system in elderly
      dipper and non-dipper hypertensive subjects. The study group consisted of twelve
      non-dipper and twelve dipper hypertensive patients (mean age 77.7 and 73.8 years,
      respectively). Non-dippers were defined as subjects whose nocturnal fall in
      systolic blood pressure (SBP), evaluated by means of Ambulatory Blood Pressure
      Monitoring, was less than 10% of diurnal SBP. All the patients underwent the
      following cardiovascular tests to explore autonomic function: Tilt Table,
      Valsalva Maneuver, Deep Breathing, Cough. The tests were performed under standard
      conditions, and heart rate and blood pressure were continuously recorded.
      Valsalva ratio (VR), Expiration/Inspiration Ratio (E/IR) and Cough Test Ratio
      (CTR) were calculated. Mann Whitney's and chi 2 tests were used for comparison
      between groups. Relationships were assessed by univariate and multivariate
      analyses. Non-dipper hypertensive subjects showed significantly lower scores in
      VR (11.1 +/- 0.08 vs 1.28 +/- 0.14), E/IR (1.11 +/- 0.07 vs 1.21 +/- 0.10), and
      CTR (1.07 +/- 0.02 vs 1.15 +/- 0.07). During the tilt test, a significant
      decrease in SBP and a late increase in heart rate were observed in non-dippers.
      The day-night difference in SBP was significantly related to VR, CTR and maximal
      SBP drop during tilting. The findings confirm that non-dippers show an impairment
      in autonomic nervous drive, which is characterized mainly by decreased
      parasympathetic activity. These observations may explain the increase in
      cardiovascular risk in non-dippers.

PMID- 9553620
TI  - The relationship between premorbid life-style and wandering behaviors in
      institutionalized people with dementia.
AB  - Forty-nine ambulatory residents participated in a study conducted to determine
      the relationship between premorbid life-style, work, and ways of handling stress,
      and wandering in dementia units. The sample consisted of 23 males and 26 females
      with a mean age of 79. Family members responded to open-ended questionnaires that
      asked about premorbid leisure activities, hobbies, exercise, stress management,
      type of employment and social interactions. Activities were ranked according to
      energy expended on the Metabolic Cost of Activities (MET) Scale. No activity
      equaled Inactive (0); 1.5-2 METS equaled Mildly Active (1), 2-3 METS equaled
      Moderately Active (2), and 3-4 METS equaled Very Active (3). Subjects were
      observed three times for one-hour intervals on each of three shifts (day,
      evening, night) at randomly selected times to assess wandering behavior. Behavior
      was logged every five minutes. The subjects' most frequent conditions were awake
      (21%), alone (20%), and in their own rooms (17%). Twenty-four (50%) of the
      subjects were observed pacing, and 16 (33%) were agitated/restless at some point
      in time. Statistical analyses showed no significant correlations between
      premorbid life-style variable rankings and the amount of time spent standing,
      walking and pacing. The findings suggest that wandering behavior is not
      influenced by premorbid life-styles.

PMID- 9553621
TI  - Effects of age and food restriction on calcium signaling in parotid acinar cells
      of Fischer 344 rats.
AB  - In this study, we characterized alpha-adrenergic (alpha AR) and muscarinic
      induced [Ca2+]i changes in individual parotid acinar cells from male Fischer 344
      rats (6-24 month-old) fed ad libitum (AL) or 60% ad libitum intake (FR). Cells
      were prepared by collagenase/hyaluronidase digestion. [Ca2+]i was measured by
      video image, fluorescent microscopy in single acinar cells loaded with FURA2.
      Neither age nor food restriction altered the peak [Ca2+]i achieved in response to
      carbachol (100 microM). Similar results were obtained for epinephrine (Epi = 100
      microM) stimulation in 6- and 12-month-old animals. However, the peak [Ca2+]i
      response to Epi declined between 12 and 18 months in both dietary groups (e.g.,
      AL: 12 months = 387 +/- 21 nM, 18 months = 253 +/- 10 nM; FR: 12 months = 430 +/-
      22 nM, 18 months = 325 +/- 14 nM). The decline in response to Epi seen with age
      was less in FR than in AL animals at 18 months, but not at 24 months. In
      addition, db cAMP reduced the carbachol-stimulated [Ca2+]i response to levels
      comparable to those observed with epinephrine. The results support the view that
      calcium mobilization in parotid acinar cells from male Fischer 344 rats in
      response to alpha AR, but not to muscarinic, stimulation is impaired with age.
      Food restriction may slow down, but does not prevent, the functional decline.
      Furthermore, cAMP appears to modulate the muscarinic response.

PMID- 9553622
TI  - Theories of aging: a pathophysiological perspective.

PMID- 9553623
TI  - Genetic theories on aging.

PMID- 9553624
TI  - Molecular, cellular and genetic determinants of aging.

PMID- 9553625
TI  - Intensive insulin treatment reduces the accumulation of oxidation and glycation
      end-products in diabetic rat collagen.

PMID- 9553626
TI  - Accumulation of dolichol and impaired signal transduction in aging.

PMID- 9553627
TI  - From the kinetics of dying to the processes of aging.

PMID- 9553628
TI  - Aging: current concepts.

PMID- 9553629
TI  - Genetic mechanisms in aging and cancer.

PMID- 9553630
TI  - Design and analysis of aging studies.

PMID- 9553631
TI  - Animal models of aging.

PMID- 9553632
TI  - Cell culture as a model for gerontological research.

PMID- 9553633
TI  - Human studies: the longitudinal approach.

PMID- 9553634
TI  - Geriatric pharmacology.

PMID- 9553635
TI  - Grant application process in USA.

PMID- 9553636
TI  - Transference and countertransference interpretations: harmful or helpful in short
      term dynamic therapy?
AB  - Finding effective and economical interventions in brief therapy has become a
      challenge for therapists of all orientations needing to make noticeable progress
      within a short period and to achieve positive, measurable outcomes. In this paper
      three theoretical positions and the empirical data purporting to support them
      were examined: (1) not using either transference or countertransference
      interpretations; (2) using transference but not countertransference
      interpretations; and (3) relying heavily on both kinds of interpretations. Though
      limited research prevents firm conclusions, findings support infrequent, careful,
      and cautious usage of transference and countertransference interpretations,
      including crafting them to meet specific patient characteristics and reflect
      presenting problems. If appropriately used, both interpretations can affect
      outcome by contributing to alliance building, perseverance in therapy, and goal
      attainment. If inappropriately used, however, both interpretations can cause
      harm, even premature termination. Finally, research findings do not support the
      theoretical position that positive outcome depends on transference and
      countertransference interpretations.

PMID- 9553637
TI  - Self-mutilation, substance abuse, and the psychoanalytic approach: four cases.
AB  - While self-injury and substance abuse are difficult symptoms for both analyst and
      patient to cope with, and relapses are frequent, the emphasis does not have to be
      on managing crisis. The initial ego support and therapeutic boundary setting in
      these difficult cases must be matched by psychoanalytic exploration. In working
      with these patients, I find that, through mutual projective identification
      processes, the analyst and the patient are frequently resurrecting certain
      aspects of the patient's archaic phantasy life as defined by various self and
      object representations. Therefore, the continuous analysis of the transference
      and the countertransference is certainly essential. However, the additional
      willingness on the part of the analyst and the patient to explore the frequent
      and mutual interpersonal/intrapsychic acting out is paramount.

PMID- 9553638
TI  - The evangelical Christian in psychotherapy.
AB  - The history of the evangelical attitudes to therapy is complex. Several of the
      historical roots to a general suspicion of psychological perceptive are explored.
      Freudian psychoanalysis and fundamentalism were not compatible and for decades no
      attempt at rapprochement developed. The liberal wing of Christianity made early
      attempts with the religion/psychiatry dialogue of the 1960s. Drastic changes in
      the youth of the evangelical, especially on the college campus in the 1960s,
      broke through some of the resistance. A growing disillusionment on the part of
      the evangelical in the pew concerning the efficacy of the traditional spiritual
      approach to relational and emotional problems accompanied these changes. The
      literalism and rigidity of a paranoid stance toward psychological insights has
      given way to a kind of chaos. The evangelical person seeks outside the church
      too. There is no consensus theoretically or practically among the many from
      within the church who are therapists. There are many strengths in the
      evangelical. These include family and developmental emphases in psychotherapy.
      The effective therapist will comfortably explore the religious life of the
      evangelical as it is relevant to the therapeutic task. Acceptance and elimination
      of countertransferential bias will foster the honesty and mutual respect that are
      essential for positive outcomes in therapy.

PMID- 9553639
TI  - Engaging in psychotherapy with the Orthodox Jew: a critical review.
AB  - A critical overview of the current knowledge of engaging in psychotherapy with a
      cultural minority, Orthodox Jews, is provided. The various forms of psychotherapy
      that have been utilized to engage Orthodox Jews in meaningful psychotherapeutic
      encounters are discussed. Psychodynamic, cognitive, behavioral, couple, family,
      and group therapies have all been employed with success. The first key in working
      with cultural minorities, including Orthodox Jews, is patience. Patience is
      required to allow a therapeutic alliance to develop in which the therapist, the
      outsider, can be trusted. When patients are reluctant to accept the treatment
      proposed, patience is necessary to give them the time required to verify the
      treatment with someone they trust, often their rabbi in the case of the Orthodox
      Jew. Patience is also valuable when patients request a change in the frame of
      therapy, such as the use of a chaperon or leaving the door slightly ajar if being
      treated by a member of the opposite sex. The second key in working with this or
      any other cultural minority is flexibility. Flexibility is required, to chose
      treatment modalities that best fit with the patient's beliefs, to respect the
      patient's beliefs no matter the extent they deviate from the therapist's own, and
      finally, to be critical of oneself when examining transference and
      countertransference reactions.

PMID- 9553640
TI  - Contemporary ethical dilemmas in psychotherapy: cosmetic psychopharmacology and
      managed care.
AB  - Two contemporary ethical dilemmas facing psychotherapists have been noted and
      described: cosmetic psychopharmacology and the practice of psychotherapy in a
      managed care environment. Regarding cosmetic psychopharmacology: It was noted
      that whether a psychotherapist endorses the use of psychotropic agents for
      cosmetic purposes, such as self-transformation, seems to be a function of the
      severity of the client/patient symptoms as well as the psychotherapist's view of
      human nature and the human condition. However, recent research indicates that
      certain traits or reflections of the human condition, such as irritability, may
      actually be neurotransmitter deficiencies that are responsive not only to
      psychotropic agents but also to non-drug interventions. These findings add an
      additional dimension to discussions of the ethics of cosmetic psychopharmacology.
      Regarding psychotherapy in a managed care environment: Several ethical dilemmas,
      including confidentiality, were discussed. These dilemmas were outlined rather
      than analyzed in detail. Some of them will become major "thorns" of concern for
      the practice of psychotherapy. Others will be less consequential. Of critical
      concern is that limitations by managed care on the technique and optimal length
      of treatment of psychotherapy can conceivably lessen its efficacy for some
      patients and could possibly eliminate this powerful treatment procedure for
      others.

PMID- 9553641
TI  - Psychoanalytic psychotherapy with traumatized refugees: integration,
      symbolization, and mourning.
AB  - The author takes as a point of departure that severe trauma, such as torture, is
      "unresolved" because it is not symbolized and is thus dissociated or existing as
      warded-off parts of the personality. Depending on the severity and character of
      the trauma, the depth of the regression experienced, and the age and life
      circumstances of the patient at the moment of trauma, this can have more or less
      severe impact on the personality structure. The consequences may at worst be
      fragmentation and total lack of trust in others. In psychotherapy these patients
      often fear retraumatization when narrating and working through their traumatic
      experiences. This pinpoints the paradoxical nature of psychotherapy, where
      painful aspects of the healing process are brought into focus. The totality of
      the psychotherapeutic situation must then explicitly be taken into consideration.
      The author discusses how different aspects of this address different aspects of
      the psychopathology of the patient. Clinical vignettes illustrate some salient
      points.

PMID- 9553642
TI  - Therapeutic approaches to problems of meaninglessness.
AB  - Paradigmatically, meaningful action, and by extension meaningful living, inhere
      in immersed participation in activities from which one derives substantial
      instrumental, intrinsic, and/or spiritual value. The greater the departure from
      this paradigm (the existentialist's "absurd" being the extreme case), the more
      meaningless will one's existence seem. Employing this paradigm case as a point of
      departure, the job of the psychotherapist becomes that of (a) diagnosing
      obstacles to clients securing such value in their behavior, and (b) assisting
      them in the removal or diminution of these obstacles. The empirically most common
      of these obstacles, as well as some therapeutic approaches to addressing them,
      have been discussed in this article.

PMID- 9553644
TI  - To a beginning psychotherapist: how to conduct individual psychotherapy.
AB  - The paper presents a realistic orientation to the practice of primarily insight
      psychotherapy. The principles, basic assumptions, and practical considerations
      are nevertheless applicable to all serious psychotherapy. Therapy is here
      understood not as a science or a matter of technique but as a collaborative and
      uniquely personal exploration of the patient's difficulties in living.
      Psychotherapy is thus seen as a search for meaning rather than for cure, with the
      hope that knowing what they are doing with their lives will enhance the ability
      of patients to live with more effectiveness and fulfillment. The limitations of
      therapy and therapists are fully recognized. Specific guidelines for initiating
      and conducting therapy are designed to promote genuine progress and reduce the
      risk of errors that are so easily made even by the experienced. As the medium of
      therapy, the patient-therapist interplay is presented from the perspective of
      both patient and therapist. The intelligent use of empathy and interpretation and
      the manifold forms of resistance all receive their share of attention. The paper
      concludes with a consideration of values, morality, and the importance of
      recognizing and respecting the spiritual dimension.

PMID- 9553643
TI  - Disguised hysteria in a child psychosis?
AB  - In this paper the stages are presented in the psychoanalysis of an eight-and-a
      half-year-old boy consulting with a worsening symptomatology that has been
      evolving for more than one year. The trigger element seems to have been the birth
      of a brother. During the analysis the relation was clear between this brother's
      birth, the mother's abortions, and the previous death of a brother. The
      interpretation of the homicidal omnipotent fantasies and the analyst's reception
      of projective identifications, destructive anxieties, and castrating anxieties of
      the patient produced, apparently, an unimagined fast improvement of the psychotic
      symptoms. This took the authors retrospectively to raise the hypothesis that this
      patient's psychosis could be a disguised child hysteria.

PMID- 9553645
TI  - The use of combined heparin/aspirin and immunoglobulin G therapy in the treatment
      of in vitro fertilization patients with antithyroid antibodies.
AB  - PROBLEM: To compare the effect of heparin/aspirin therapy alone vs.
      heparin/aspirin in combination with intravenous immuno-globulin (IVIg)
      immunotherapy on in vitro fertilization (IVF) outcome of patients who test
      positive for antithyroid antibodies (ATAs). METHOD OF STUDY: Eighty-two women
      younger than 40 years of age whose infertility was related exclusively to female
      causes were evaluated. All tested positive for organ-specific antithyroid
      antibodies (antimicrosomal and/or antithyroglobulin antibodies), but negative for
      antiphospholipid antibodies. Thirty-seven of these women (group A) received H/A
      alone, whereas 45 (group B) received heparin/aspirin in combination with IVIg.
      RESULTS: Ten (27%) of women in group A and 23 (51%) of women in group B achieved
      live births after completion of a single IVF/embryo transfer cycle (P = 0.027).
      CONCLUSION: We conclude that IVIg therapy significantly improves IVF success
      rates in ATA+ women.

PMID- 9553646
TI  - Experimental autoimmune prostatitis: in vivo induction of the autoimmune response
      to lymphocytic soluble factors. Alterations at the endocrine metabolism level.
AB  - PROBLEM: In rats, immunization with male accessory gland (MAG) extract promotes
      experimental autoimmune vesicle prostatitis. A specific mononuclear cell-mediated
      immune response and prostate androgen metabolism impairment in MAG-immunized rats
      were observed. The possibility that lymphocytic soluble factors (SoFs) can
      regulate the local steroid metabolism in these rats directly was studied. We
      investigated whether the SoFs released by MAG-sensitized lymphocytes are capable
      of modifying the prostatic androgen metabolism and whether they induce histologic
      lesions "in vivo" when they are inoculated, carried by liposomes, into untreated
      rats. METHOD OF STUDY: "In vitro" enzymatic [3H]-5 alpha-dihydrotestosterone
      bioconversion and histologic studies were performed with prostates from SoF
      treated rats (LK rats). The obtained 3 alpha/beta-hydroxysteroid-oxidoreductase
      activities showed that LK rat values were significantly lower than in controls:
      79.0 +/- 2.5 vs 158.7 +/- 10.2 pmol/min/mg protein, respectively (P < 0.01).
      RESULTS: In the histologic studies, LK rat prostates showed focalized mononuclear
      infiltrates of various degrees, whereas control rats showed non-atypic
      modification of the gland. CONCLUSION: These results indicate that SoFs (probably
      total lymphokines) contribute significantly to the pathogenesis of experimental
      autoimmune prostatitis, involving a biochemical relationship between immune
      reaction and the androgenic enzymatic inhibition in the prostate.

PMID- 9553647
TI  - Effects of antibodies to transferrin and alpha 2-HS glycoprotein on in vitro
      sperm motion: implications in infertility associated with endometriosis.
AB  - PROBLEM: Women with endometriosis have antibodies to endometrial transferrin and
      alpha 2-HS glycoprotein in their serum and peritoneal fluid. The objective of
      this study was to determine whether antibodies to transferrin and alpha 2-HS
      glycoprotein adversely affect sperm motility and survival. METHOD OF STUDY:
      Spermatozoa obtained from normal fertile donors and washed free of seminal plasma
      were incubated with the medium (control), 1:2 and 1:100 dilutions of
      antitransferrin, 1:4, 1:8 and 1:100 dilutions of anti-alpha 2-HS glycoprotein,
      and a 1:2 dilution of antialbumin antiserum (negative control). Sperm motion
      characteristics in 10 microliters aliquots were evaluated at 30 min, 1 hr, 2 hr,
      4 hr, and 24 hr using computerized sperm motion analysis. A paired t-test was
      done to analyze the effects of the various antibodies on sperm motion
      characteristics. RESULTS: Antibodies to albumin failed to adversely affect sperm
      motility in general or the several sperm motion characteristics in particular. In
      contrast, antibodies to transferrin at the dilution of 1:2 adversely affected the
      percentage of motile and rapid spermatozoa, progressive and path velocities,
      straightness, linearity, track speed, and anterior-lateral head displacement (P <
      0.001) at all the time intervals, whereas a 1:100 dilution of this antiserum
      adversely affected these parameters only at 24 hr. Elongation and beat cross
      frequency were significantly affected at 4 and 24 hr by a 1:2 dilution of
      antitransferrin antiserum. The effects of anti-alpha 2-HS glycoprotein were more
      pronounced than those of antitransferrin, but they were similar. Dilutions of 1:4
      and 1:8 were effective at all time intervals, whereas a 1:100 dilution was
      effective in reducing the track speed and the percentage of rapid cells at 24 hr
      (P < 0.001). CONCLUSION: Antibodies to endometrial transferrin and alpha 2-HS
      glycoprotein present in the peritoneal fluid, and possibly in the oviductal
      fluid, of patients with endometriosis may adversely affect postcoital sperm
      motility and sperm survival.

PMID- 9553648
TI  - Complement regulatory proteins on the sperm surface: relevance to sperm motility.
AB  - PROBLEM: To determine whether complement regulatory proteins are present on human
      spermatozoa and whether antibodies to these proteins adversely affect sperm
      motility. METHOD OF STUDY: Human sperm membrane proteins were solubilized and
      subjected to polyacrylamide gel electrophoresis followed by Western blot analysis
      against antibodies to complement component 1 inhibitor (C1-INH), decay-activating
      factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and homologous
      restriction factor (HRF; CD59). Spermatozoa, obtained by a swim-up technique,
      were incubated in medium (control 1) and medium supplemented with antibodies to
      human albumin (control 2) and antibodies to these complement regulatory proteins.
      We used a computerized sperm motion analysis to determine the effect of these
      antibodies on sperm motion characteristics. RESULTS: Complement regulatory
      proteins such as C1-INH, CD55, CD46, and CD59 were found in the sperm extracts as
      shown by Western blot analysis. The heat-treated (56 degrees C, 30 min) IgG
      fraction of antibodies to these proteins significantly reduced sperm motility in
      general and other motion parameters. Addition of complement did not affect these
      results except in the antibodies to CD46 in which the reducing action was further
      amplified. CONCLUSIONS: Our data suggest that C1-INH, CD55, CD46, and CD59 are
      present on the sperm surface. These proteins may have biological functions, such
      as affecting sperm motility, besides the complement regulatory functions. In
      infertile men and women with antibodies that recognize one or more of these
      complement regulatory proteins, there may be problems related to poor sperm
      motility and survival in the reproductive tracts.

PMID- 9553649
TI  - The herbal medicine unkei-to stimulates cytokine-induced neutrophil
      chemoattractant production in the pituitary folliculo-stellate-like cell line
      (TtT/GF).
AB  - PROBLEM: We previously reported that a cytokine-induced neutrophil
      chemoattractant (CINC) was produced in the pituitary gland and that it influenced
      anterior pituitary hormone release. In this study we investigated the effect of
      Unkei-to, a Japanese herbal medicine, on CINC production in the rat anterior
      pituitary gland and the pituitary folliculo-stellate-like cell line (TtT/GF).
      METHOD OF STUDY: Dispersed normal anterior pituitary cells and the folliculo
      stellate-like cell line TtT/GF were used to test the effect of Unkei-to on CINC
      secretion and CINC mRNA accumulation. Concentrations of CINC in the conditioned
      media were measured by an enzyme-linked immunosorbent assay, and levels of CINC
      mRNA were analyzed by Northern blot analysis. RESULTS: Unkei-to (20
      micrograms/ml) significantly increased the secretion of CINC by normal anterior
      pituitary cells within 12 hr of incubation. Unkei-to also stimulated CINC
      secretion from TtT/GF cells in a time- and dose-dependent manner. Unkei-to (20
      micrograms/ml) increased CINC mRNA accumulation in TtT/GF cells within 3 hr of
      incubation and also caused a 13-fold increase in the secretion of CINC from
      TtT/GF cells compared with the vehicle group within 24 hr of incubation. Finally,
      we found that some of the Unkei-to's ingredients, Evodiae fructus and Pinelliae
      tuber, markedly stimulated CINC secretion from TtT/GF cells. CONCLUSIONS: Our
      results will help to elucidate the mechanism behind the clinical effect of Unkei
      to on the anterior pituitary gland. They also suggested the presence of special
      substances, which stimulate CINC secretion, within Unkei-to's ingredients such as
      E. fructus and P. tuber.

PMID- 9553650
TI  - Changes in lymphoid tissue after treatment with a gonadotropin releasing hormone
      antagonist in the neonatal marmoset (Callithrix jacchus).
AB  - PROBLEM: The effect of neonatal treatment with a gonadotropin releasing hormone
      (GnRH) antagonist on the morphology and distribution of lymphocytes in lymphoid
      tissue of the infant marmoset was examined. METHOD OF STUDY: From a screened
      panel of antihuman antibodies for specific immune cells, antibodies for the CD20
      and CD3 antigens showed excellent reactivity with marmoset tissue. Five sets of
      marmoset twins were treated with either the GnRH antagonist or a vehicle from
      birth, and were euthanized at 7 to 9 (3 sets) or 16 to 20 weeks (2 sets) of age.
      The spleen, thymus, and inguinal lymph nodes from each animal were processed for
      immunocytochemistry, and the number of cells expressing the CD20 and CD3 antigens
      were quantified. RESULTS: Control twins exhibited high plasma levels of
      testosterone, characteristic of the neonatal period, whereas testosterone
      concentrations were reduced (P = 0.001) to detection limits in the GnRH
      antagonist-treated twins. Microscopic evaluation suggested that treatment reduced
      the volume and cellularity of the thymic cortex, resulting in a decrease in the
      cortical-to-medullary ratio. Treatment reduced (P = 0.046) the number of
      thymocytes expressing the B-cell antigen (CD20) and marginally lowered (P =
      0.067) the number expressing the T-cell antigen (CD3) in the thymic medulla. In
      the spleens of treated animals, periarterial lymphatic sheaths were less
      prominent on microscopic examination, and there were marginally fewer (P = 0.064)
      CD3+ cells. Numbers of CD20+ lymphocytes in the peripheral white pulp of the
      spleen and in the germinal centers of the lymph nodes, or CD3+ cells in the
      paracortex and germinal centers of the lymph nodes, were not altered by
      treatment. CONCLUSION: Neonatal treatment with a GnRH antagonist may alter
      maturational processes for B and T cells in the thymus and spleen of the marmoset
      and may deprive the immune system of its normal sensitivity to GnRH at a
      potentially critical time in development.

PMID- 9553651
TI  - Adenosine deaminase and human reproduction: a comparative study of fertile women
      and women with recurrent spontaneous abortion.
AB  - PROBLEM: We have investigated the possible role of adenosine deaminase (ADA)
      genetic polymorphism in human fertility through a comparative study of couples
      with recurrent spontaneous abortion (RSA) and healthy puerperae. METHOD OF STUDY:
      Adenosine deaminase phenotype has been determined in 209 women with repeated
      episodes of unexplained spontaneous abortion (RSA) and their husbands, as well as
      in 115 healthy pregnant women from the population of Rome. An independent sample
      of 286 puerperae along with their newborn infants in the population of Penne was
      also studied. RESULTS: The proportion of carriers of ADA*2 allele, which is
      associated with the lowest enzymatic activity, is lower among women with RSA than
      among healthy pregnant women from the same population of Rome. Preliminary
      observations suggest a protective effect of ADA*2 against the development of
      autoantibodies in RSA. Such an effect seems to be mediated by an interaction with
      AB0 blood groups. In the population of Penne the proportion of women carrying
      ADA*2 allele is higher among those who have had two or more previously born
      children than among women with only one or no children. CONCLUSIONS: The data
      suggest that women carrying the ADA*2 allele are better protected against the
      spontaneous loss of embryos and have a higher fertility rate.

PMID- 9553652
TI  - Human lymphocytes obtained from decidual tissue express killer activatory
      receptors as well as killer inhibitory receptors: analysis using a single strand
      conformation polymorphism method.
AB  - PROBLEM: The objective was to clarify whether lymphocytes in decidual tissue
      express only killer inhibitory receptors (KIRs) or both KIRs and killer
      activatory receptors (KARs). METHOD OF STUDY: A polymerase chain reaction (PCR)
      single strand conformation polymorphism (SSCP) analysis method, using cDNA as a
      template, was applied to detect as many natural killer receptors (NKRs) expressed
      on natural killer (NK) cells as possible and to distinguish between KIRs and
      KARs. Using this method, we analyzed NKRs on lymphocytes in decidual tissue and
      maternal peripheral blood mononuclear cells (PBMCs) (n = 10) from the same
      individuals. RESULTS: More than 20 SSCP bands were detected for NKRs on both the
      lymphocytes in decidual tissue and the maternal PBMCs. The SSCP band patterns
      were different for each individual. KARs mRNA was detected in lymphocytes in
      decidual tissue according to the SSCP analysis results. CONCLUSION: Lymphocytes
      in decidual tissue express not only KIRs but also KARs; this finding suggests
      their roles in placentation and the maintenance of pregnancy.

PMID- 9553653
TI  - How might pregnancy immunize against breast cancer?
AB  - PROBLEM: This study investigated how pregnancy might protect against breast
      cancer. METHOD OF STUDY: A critical review of the literature was done.
      RESULTS/CONCLUSIONS: Support for an active role in pregnancy immunizing against
      breast cancer comes from case studies demonstrating a reciprocal correlation
      between pregnancy and breast cancer as well as recent experiments supporting the
      fetal antigen hypothesis that confirms the presence of a tumor-specific antigen,
      MUC1, on both fetal and breast cancer tissues. Multiparous women also generate
      anti-MUC1 major histocompatibility complex-restricted cytotoxic T cell cytolytic
      activity against MUC1-bearing tumor cell lines. Careful investigation of the
      fetal antigen hypothesis and tolerogenic mechanisms may lead to effective
      vaccination protocols against breast cancer and other cancers.

PMID- 9553654
TI  - Transferrin receptor (CD71) expression in peritoneal macrophages from fertile and
      infertile women with and without endometriosis.

PMID- 9553655
TI  - Understanding and overcoming resistance to chemotherapy in acute myeloid
      leukemia.

PMID- 9553656
TI  - High-dose chemotherapy for chronic lymphocytic leukemia: eligibility, timing, and
      benefit?

PMID- 9553657
TI  - The changing landscape of breast cancer clinical research. ESMO-Award Lecture,
      ECCO-9 Hamburg, 18 September 1997.
AB  - Clinical research for breast cancer is moving in three new directions following:
      1) a critical analysis of three decades of randomized clinical trials for early
      disease; 2) increasing awareness of this lethal disease among women, generating
      women's associations which are pressing for improved breast cancer education,
      screening and treatment; 3) an exponential growth in our understanding of breast
      cancer molecular biology, leading to a number of innovative therapies with new
      targets in the cancer cell or its environment. It is the remarkable work of the
      Oxford Group which has finally vindicated the use of our three main weapons
      against breast cancer micro-metastases, namely tamoxifen, chemotherapy and
      ovarian ablation. There is now consensus that clinical research in the adjuvant
      setting may gain speed and efficiency through intergroup collaboration. Such an
      'Intergroup' has been recently created in Europe and will collaborate with the
      American-Canadian Intergroup. Women's associations have only recently stepped
      forward to demand better care, and more effective therapies: they are becoming
      new partners in identifying critical issues in breast cancer research. Medical
      oncologists involved in breast cancer research are facing a new challenge: the
      optimal integration of traditional breast cancer therapies, namely endocrine
      treatments and chemotherapy, and entirely new strategies targeting signal
      transduction, apoptosis or angiogenesis. In view of the above, there is no doubt
      that we are entering a new and exciting era in breast cancer clinical research.

PMID- 9553658
TI  - Malignant pleural mesothelioma.

PMID- 9553659
TI  - Autologous peripheral blood progenitor cell transplantation mobilized with high
      dose cytarabine in acute myeloid leukemia in first complete remission.
AB  - BACKGROUND: The aim of this study was to increase disease-free survival (DFS) in
      AML in CR1 using a high-dose cytarabine consolidation plus G-CSF as in vivo
      purging and mobilization of CD34+ cells before ablative therapy and peripheral
      blood autograft. PATIENTS AND METHODS: Fifty-six consecutive AML patients (pts)
      (including 11 children < 15 years), with a median age of 32 years, were analyzed.
      After achievement of CR with cytarabine-mitoxantrone (7 + 3) in adults and a BFM
      like protocol in children, pts were intensified with cytarabine 2 g/m2 x six
      doses plus mitoxantrone for adults, or, 3 g/m2 x six doses plus etoposide for
      children, followed by G-CSF 5 micrograms/kg SC daily. The ablative regimens used
      were busulfan and cyclophosphamide (Bu/Cy) in standard-risk pts plus etoposide
      (2400 mg/m2) for high-risk pts. RESULTS: For the 54 pts who underwent autologous
      transplant, the median time to reach > 1.0 x 10(9)/l neutrophils was 13 days (8
      48), and to reach platelets > 25 x 10(9)/l 32 days (8-364), and the median
      numbers of red blood cell and platelet units transfused were 3 and 5,
      respectively. Six pts had treatment-related deaths (11%). The disease-free
      survival and overall survival at 30 months (mos) for the 56 eligible pts were 61%
      and 62%, respectively. Only two relapses were observed after 21 mos, while there
      were 12 relapses within 12 mos. CONCLUSIONS: The above treatment results in a
      similar DFS rate as does rescue with bone marrow cells, with faster neutrophil
      and platelet recovery.

PMID- 9553660
TI  - High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid
      leukemia.
AB  - BACKGROUND: The bcl-2 oncoprotein is suggested to be directly involved in the
      emergence of drug resistance by disrupting or delaying the apoptotic program and
      promoting tumor survival. PATIENTS AND METHODS: In order to define the clinical
      relevance of the bcl-2 mRNA expression in acute myeloid leukemia (AML) and its
      correlation to therapy outcome and prognosis, we analyzed 219 AML bone marrow
      (BM) samples, including 119 patients with de novo AML at presentation, 37 with
      AML following myelodysplastic syndrome (MDS), as well as 42 BM samples of AML in
      relapse and 21 in complete remission (CR) using RT-PCR. For performing
      quantitative measurements of bcl-2 mRNA, we developed a quantitative RT-PCR.
      RESULTS: Bcl-2 mRNA was detectable in 133 of 156 (84%) patients at diagnosis and
      40 of 42 (95%) at relapse. AML patients with high bcl-2 mRNA expression achieved
      lower CR rates than those with no or low expression. Concerning the long-term
      outcome, the overall (OS) and disease-free survival (DFS) was significantly worse
      in AML patients with high expression levels of bcl-2 mRNA. The three-year OS for
      all newly diagnosed AML patients was 49% and 10% (P = 0.028), respectively, and
      71% and 15% (P = 0.0004) for patients < 60 years. Comparable significant
      differences were observed for the DFS. In AML following MDS and patients > 60
      years, the bcl-2 expression was not associated with remission rate or survival.
      CONCLUSIONS: The expression of bcl-2 mRNA may serve as a prognostic factor
      predicting remission outcome and long-term prognosis in AML.

PMID- 9553661
TI  - Hematopoietic stem cell transplantation in chronic lymphocytic leukemia: a report
      of 12 patients from a single institution.
AB  - BACKGROUND: Stem-cell transplantation is a reasonable therapeutic approach for
      younger patients with high-risk CLL. PATIENTS AND METHODS: Twelve patients (seven
      males; median age 47 years, range 29-51) with high-risk CLL underwent
      transplantation (allo, n = 7; auto, n = 5). The conditioning regimen consisted of
      cyclophosphamide and total body irradiation in 11 patients, and BEAC in the
      remaining one. Minimal residual disease (MRD) was assessed by cytofluorometry and
      PCR. RESULTS: All 11 evaluable patients engrafted. Of the seven allografted
      patients, two died of treatment-related causes; three patients developed acute
      GVHD. No transplant-related mortality was observed in autografted patients. After
      transplantation, 10 of 11 patients evaluable for response achieved CR (91%; 95%
      CI 59%-100%) which was molecular in nine patients (82%; 95% CI 48%-98%). One
      patient in CR but MRD+ relapsed nine months after transplantation and died. Seven
      patients remain in molecular CR for a median of 16 months (range 1-58). Estimated
      actuarial survival and disease-free survival at two years is 81% (95% CI 43%
      100%) and 71% (95% CI 43%-99%), respectively. Relapse risk at two years is 12.5%
      (95% CI 0%-35.5%). CONCLUSIONS: Patients with high-risk CLL can achieve long
      lasting molecular CR after SCT. The role of transplants in CLL management
      deserves investigation in controlled trials.

PMID- 9553662
TI  - High-dose topotecan with granulocyte-colony stimulating factor in
      fluoropyrimidine-refractory colorectal cancer: a phase II and pharmacodynamic
      study.
AB  - PURPOSE: The premise for this study was that topotecan (TPT) resistance in
      preclinical studies is associated with low level expression of the p-glycoprotein
      (Pgp) multi-drug transporter conferred by the multi-drug resistant (MDR)
      phenotype, which might be overcome in clinical practice by administering
      moderately (2.3-fold) higher doses of TPT that have shown to be feasible with
      granulocyte colony-stimulating factor (G-CSF) support. This phase II study
      evaluated the anti-tumor activity of TPT administered at its highest possible
      solid tumor dose with G-SCF in patients with fluoropyrimidine-refractory advanced
      colorectal carcinoma. The study also sought to identify pharmacodynamic (PD)
      determinants of both activity and toxicity. PATIENTS AND METHODS: TPT was
      administered as a 30-minute infusion daily for five days every three weeks at a
      dose of 3.5 mg/m2/day to patients with advance colorectal carcinoma who developed
      progressive disease either during treatment with fluoropyrimidine-based
      chemotherapy for advanced disease or within six months after receiving
      fluoropyrimidine-based adjuvant chemotherapy. This dose of TPT was previously
      determined to be the maximal tolerated dose (MTD) with G-CSF support in a phase I
      study involving solid tumor patients with similar risk factors for
      myelosuppression. Plasma sampling with performed during course 1 to characterize
      the pharmacokinetic (PK) and PD behavior of TPT. RESULTS: Seventeen patients who
      received 89 courses of TPT and G-CSF were evaluable for toxicity; 16 patients
      were evaluable for anti-tumor response. Toxicity, particularly myelosuppression,
      was substantial. At the 3.5 mg/m2/day dose level, absolute neutrophil counts
      (ANC) were less than 500/microliters for longer than 5 days in 17% of courses
      involving seven of seventeen (41%) patients. Severe neutropenia associated with
      fever occurred in 12.3% of courses; and platelet counts below 25,000/microliters
      were noted in 26.9% of courses. These toxicities resulted in dose reductions in
      seven of 17 (41%) patients. Nevertheless, 90% of the planned total dose of TPT
      was administered. No major responses were observed, though minor activity was
      noted in several patients. Both the median time to progression and the median
      survival time were short--2.5 and 4 months respectively. Although interindividual
      variability in the disposition of total TPT was observed, the lack of objective
      responses precluded PD assessments related to disease activity. Total TPT
      exposure was significantly higher than drug exposure achieved in similar patients
      at an identical dose in a previous phase I study of TPT and G-CSF, which may
      explain why more severe myelosuppressive effects occurred in the present study.
      There were no PD relationships evident between relevant PK parameters and the
      percent decrements in platelets and ANC's during course 1, although patients with
      severe toxic effects (ANC below 500/microliters for more than five days and/or
      platelets < 25,000/microliters) had higher drug exposure than patients with less
      severe toxicity (P < 0.018 and P = 0.09, respectively). CONCLUSIONS: Based on
      these results, the true response rate of TPT at its solid tumor MTD with G-CSF
      support is unlikely to approach 20%. Although a response rate of less than 20%
      might be viewed as significant in this disease setting and might be confirmed
      with sufficient statistical certainty by treating additional patients, the
      substantial toxicity, inconvenience, and cost associated with this high dose
      TPT/G-CSF regimen does not warrant the acceptance of a lower level of anti-tumor
      activity as a criterion for further development.

PMID- 9553663
TI  - Positive immunostaining with MLuC1 of bone marrow aspirate predicts poor outcome
      in patients with small-cell lung cancer.
AB  - BACKGROUND: Immunocytochemistry has been proven able to identify tumor cells in
      bone marrow aspirate (BMA) of patients with SCLC. However, few data exist about
      the clinical significance of the procedure. PATIENTS AND METHODS: 108 BMA taken
      from 60 patients were incubated with the MoAb MLuC1 (cluster 6) and stained by
      the APAAP (alkaline phosphatase-antialkaline phosphatase) method. The serum
      levels of LDH, TPA, NSE and CEA were also studied in relation to bone marrow
      involvement by means of discriminant analysis. RESULTS: Immunocytochemistry of
      the aspirate with MLuC1 detected positive cells in 23 patients (38%) (38 of 108
      samples) vs. 13% of the conventional biopsies studied without MLuC1 (P < 0.001).
      With respect to bone marrow positivity, three groups of patients were identified:
      those with no positive cells in the aspirate and negative biopsy (group A); those
      with less than 10 positive cells in the aspirate and negative biopsy (group B);
      and those with more than 10 positive cells or clumps in the aspirate or positive
      biopsy (group C). Group C patients had poorer median survivals than those in the
      other two groups (5.5 vs. 11 months, respectively, P = 0.01). Discriminant
      analysis showed that the four serum markers were poor discriminators of the
      degree of bone marrow involvement, with only 55% of grouped cases being correctly
      classified. CONCLUSIONS: These results show that detection of bone marrow
      involvement i) can be improved by the use of MLuC1 ii) is not predictable by
      conventional tumor markers, and iii) is related to poor outcome.

PMID- 9553664
TI  - The role of pneumatic compression in the treatment of postmastectomy lymphedema.
      A randomized phase III study.
AB  - BACKGROUND: Pneumatic compression is a frequently prescribed physical therapy for
      patients affected by postmastectomy lymphedema but, despite its wide use, its
      efficacy has not been demonstrated in phase III studies. We performed a
      randomized study comparing pneumatic compression versus no treatment in patients
      with postmastectomy lymphedema. PATIENTS AND METHODS: Patients with monolateral
      postmastectomy lymphedema were randomized to receive two cycles of intermittent
      pneumatic compression (PC group), i.e., five two-hour sessions per week for two
      weeks, to be repeated after a five-week interval, or to no treatment (control
      group). The patients in both groups were instructed as to the prophylactic
      hygienic care of the limb. Lymphedema was assessed by the sum of differences in
      circumference measurements between affected and normal limbs ('delta'). Response
      was defined as a > or = 25% reduction in delta value. RESULTS: Eighty patients
      entered the study. No statistically significant differences in response rates
      between the two groups were observed: 20% in the control group (95% CI: 9%-36%),
      25% in the PC group (95% CI: 13%-41%, P = 0.59). The absolute mean decrease in
      delta value was 1.9 +/- 3.7 cm in the PC group and 0.5 +/- 3.3 cm in the control
      group. CONCLUSIONS: We demonstrated that intermittent pneumatic compression has a
      limited clinical role in the treatment of postmastectomy lymphedema. Efforts to
      prevent this complication should be undertaken.

PMID- 9553665
TI  - For which patients with aggressive non-Hodgkin's lymphoma is prophylaxis for
      central nervous system disease mandatory? Dutch HOVON Group.
AB  - PURPOSE: Data of a multicenter study in non-Hodgkin's lymphoma (NHL) by the Dutch
      Hovon Group were reanalyzed to assess the risk of relapse in the central nervous
      system (CNS) related to the international risk index for NHL. In addition we
      assessed the risk for CNS disease in relation to the presence of bone marrow
      localisation at presentation. DESIGN: We focused our analysis on those patients
      reaching a complete remission (CR). Two hundred eighty-six patients (histological
      subtypes D-H Working Formulation) and with stages II-IV were analyzed. One
      hundred ninety-three (67%) patients reached a CR. RESULTS: Relapse occurred in 78
      patients of whom 10 patients with concomitant or isolated CNS disease. According
      to the international risk index the following observations were made: low risk (n
      = 38) nine out of 34 CR relapsed, none had CNS involvement; low-intermediate risk
      (n = 115) 27 out of 83 CR relapsed, three had CNS involvement; high-intermediate
      risk (n = 110) 37 out of 68 CR relapsed, six had CNS involvement; high risk (n =
      22) four out of seven CR relapsed, one had CNS involvement. Two out of 10
      developed isolated CNS disease and eight out of 10 patients developed CNS disease
      with systemic relapse. CONCLUSION: Our data show that the number of CNS relapses
      after CR is relatively low (10 out of 193 = 5%), with an increasing incidence in
      the high-risk groups according to the international risk index. The occurrence of
      CNS relapse seems to be related to the risk of systemic relapse after CR. No
      subgroup could be discriminated in which prophylactic treatment would be of
      substantial benefit.

PMID- 9553666
TI  - Ten-year results of a strategy combining three cycles of ABVD and high-dose
      extended irradiation for treating Hodgkin's disease at advanced stages.
AB  - BACKGROUND: The treatment of Hodgkin's disease (HD) at advanced stages relies
      mainly upon multi-agent chemotherapies (CT), while the role of radiation therapy
      has not been definitely identified. The aim of this report is to analyze the 10
      year results of a prospective study including 133 patients with HD clinical
      stages (CS) IIIA to IVB treated by three monthly courses of ABVD (adriamycin,
      bleomycin, vinblastin, and dacarbazine) followed by high-dose subtotal or total
      lymphoid irradiation [(S)TLI]. PATIENTS AND METHODS: From 1 October 1981 to 30
      September 1988, 133 adult patients with HD CS IIIA (45), IIIB (33), IVA (seven)
      and IVB (48) were entered in the non-randomized multicentric prospective trial
      POF81/34. The number of involved nodal areas (NINA), and the number of visceral
      sites (NVIS) involved were registered in all patients; patients with bulky
      mediastinal tumor (BuMT) (mediastinal mass ratio > or = 0.45) were also
      identified. All patients received three monthly cycles of ABVD. Patients in
      complete remission (CR) or partial remission (PR) after completion of CT received
      a (S)TLI including the spleen (involved sites 40 Gy, non-involved 30 Gy);
      initially involved lung(s) and liver received 18 and 20 Gy, respectively; and
      patients not in CR or PR after CT or RT received salvage treatments. Univariate
      and multivariate analyses were performed to identify the factors contributing
      significantly to the prognosis; initial characteristics, as well as status after
      the three cycles of CT, were entered in the model. RESULTS: Of the 133 patients,
      74 (55.6%) entered in CR after CT and 116 (87.2%) after completion of radiation
      therapy. Ten-year freedom from progression (FFP), freedom from tumor mortality
      (FFTM) and survival rates were 70.4%, 78.9% and 70.6%, respectively. According to
      univariate analysis the NVIS (< or = one vs. > or = two) was the only initial
      factor simultaneously influencing 10-year FFP (73.9% vs. 38.2%) FFTM (82.5 vs.
      34.1%) and survival (73.5% vs. 17.3%) rates; on the other hand, the NINA (< or =
      four vs. > or = five) influenced FFP (81.4% vs. 60.7%) and FFTM rates (87.3% vs.
      71.4%) while symptoms (A vs. B) influenced FFP (80.7% vs. 63.3%) and survival
      (82.8% vs, 61.2%) rates. Finally, age (< 40 vs. > or = 40) influenced survival
      rate only (79.2% vs. 50%). According to multivariate analysis, NVIS and NINA had
      an independent impact on FFP and FFTM, while survival was modified by the NVIS
      and age. The post-CT status (CR vs. no CR) had a major impact on FFP (85.3% vs.
      64.9%) FFTM (92.1% vs. 63.3%) as well as on survival (78.6% vs. 54.7%) rates in
      both univariate and multivariate analyses. Complications of therapy were mainly
      due to RT: 11 patients acquired second malignancies, six developed lung fibrosis
      or severe pulmonary infections, three developed intestinal obstructions and six
      developed angina pectoris or carotid stenosis. CONCLUSIONS: Tumor burden
      (identified by the number of involved nodal areas and the number of visceral
      sites) and the response to initial CT were the two independent factors
      influencing the outcome of this group of 133 patients with HD, CSIII and IV
      treated by three cycles of ABVD followed by high-dose [(S)TLI].

PMID- 9553667
TI  - The anti-proliferative effect of suramin towards tamoxifen-sensitive and
      resistant human breast cancer cell lines in relation to expression of receptors
      for epidermal growth factor and insulin-like growth factor-I: growth stimulation
      in the presence of tamoxifen.
AB  - BACKGROUND: A significant proportion of breast cancer patients receiving
      tamoxifen therapy relapse during treatment following acquisition of tamoxifen
      resistant or oestrogen-independent phenotypes. The mechanism behind this rapid
      progression to oestrogen autonomy is at present unclear and further treatment
      modalities are limited. Suramin represents a novel potential second line therapy.
      The mechanism of the antineoplastic activity of suramin is not completely
      understood, although the drug binds to many growth factors including epidermal
      growth factor and insulin-like growth factors and can also dissociate growth
      factors from their receptors. In this study we have related suramin sensitivity
      to the expression of receptors for epidermal growth factor and insulin-like
      growth factor-I in a number of breast cancer cell lines including lines resistant
      to tamoxifen. MATERIALS AND METHODS: The anti-proliferative effects of suramin
      were investigated in two oestrogen dependent breast cancer lines (ZR-75-1 and MCF
      7), oestrogen independent (ZR-PR-LT) and tamoxifen resistant (ZR-75-9a1) variants
      of ZR-75-1 and a tamoxifen resistant (LY2) variant of MCF-7. Full dose response
      curves were constructed and IC50 values determined for each cell line.
      Sensitivity to suramin was correlated with the level of expression of receptors
      for epidermal growth factor (EGFR) and insulin-like growth factor-I (IGFR). On
      observing stimulation of cell proliferation by suramin in the tamoxifen resistant
      cell lines in the presence of tamoxifen we also investigated the possible role of
      suramin sequestration of transforming growth factor-beta in mediating this
      effect. RESULTS: All cell lines exhibited a dose- and time-dependent response to
      suramin treatment. Tamoxifen resistant ZR-75-9a1 cells (day 6 IC50 85 micrograms
      ml-1) were more resistant to suramin than oestrogen independent ZR-PR-LT cells
      (day 6 IC50 45 micrograms ml-1), and the parent ZR-75-1 line (day 6 IC50 56
      micrograms ml-1). Increased sensitivity to suramin was associated with increased
      expression of IGFR and decreased expression of EGFR. Tamoxifen resistant LY2
      cells were significantly more sensitive to suramin (day 6 IC50 70 micrograms ml
      1) than MCF-7 cells (day 6 IC50 350 micrograms ml-1). Both IGFR and EGFR
      expression by LY2 cells was lower than in the parent line. The antioestrogen
      resistant ZR-75-9a1 and LY2 lines grown in the presence of 8 microM tamoxifen
      were growth stimulated by concentrations of the drug below 100 micrograms/ml. As
      growth stimulation observed in the presence of tamoxifen may have been due to
      suramin sequestration of tamoxifen induced TGF-beta 1 secretion we also
      investigated the response of the cells to this peptide in the presence and
      absence of suramin. All cell lines were growth inhibited by TGF-beta 1 except ZR
      75-9a1 which was unresponsive. Responses to TGF-beta 1 were modified in the
      presence of 100 micrograms suramin ml-1 although TGF-beta 1 was unable to mimic
      the ability of tamoxifen to stimulate proliferation in the presence of suramin.
      CONCLUSIONS: These results suggest that for ZR-75-1 cells and variants, increased
      sensitivity to suramin is associated with an increase in expression of IGFR and a
      decrease in EGFR numbers. However, tamoxifen resistant LY2 cells, in which both
      IGFR and EGFR expression is reduced were considerably more sensitive than
      parental MCF-7 cells suggesting that there is no clear relationship between EGFR
      and IGFR expression and suramin sensitivity. The unexpected stimulation of cell
      proliferation of the tamoxifen resistant variants by suramin in the presence of
      tamoxifen could not be explained by suramin sequestration of transforming growth
      factor-beta and the mechanism of this interaction remains unclear.

PMID- 9553668
TI  - Detection of primary breast cancer presenting as metastatic carcinoma of unknown
      primary origin by 111In-pentetreotide scan.
AB  - Women with isolated metastatic carcinoma or adenocarcinoma involving axillary
      lymph nodes are a well-recognized group of unknown primary carcinoma (UPC)
      patients with a favorable prognosis. This group of patients are generally treated
      based on the assumption that they have occult breast cancer. However, to
      facilitate patient access to the whole spectrum of therapies available for
      patients with breast cancer, including strategies involving the use of high-dose
      chemotherapy, a precise diagnosis is increasingly important. In this clinical
      case we report the detection of a primary breast cancer by 111In-pentetreotide
      scanning in a woman who presented with metastatic carcinoma in axillary nodes, no
      palpable breast lesion, a nondiagnostic mammogram, and negative breast
      ultrasonography. Previous outcomes analysis of patients with UPC have emphasized
      the value of identifying women with breast cancer. This report suggests that the
      111In-pentetreotide scan can contribute specific, clinically useful information
      in the evaluation of women presenting with metastatic carcinoma in axillary nodes
      and an occult primary and deserves prospective study in women with UPC presenting
      with isolated axillary metastases.

PMID- 9553669
TI  - A phase II study of oral clofazimine in unresectable and metastatic
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma is highly refractory to most
      chemotherapeutic agents. Clofazimine, a riminophenazine compound used to treat
      leprosy since 1962, inhibits various cancer cell lines, including hepatocellular
      carcinoma cell lines, via phospholipase A2 dependant processes. Clofazimine also
      inhibits p170-glycoprotein, the mdr1 gene product. PATIENTS AND METHODS: Thirty
      patients (26 males and four females) with unresectable (25) or metastatic (5)
      hepatocellular carcinoma received oral clofazimine 600 mg daily for two weeks,
      followed by 400 mg daily until progression or death. RESULTS: There were three
      responses (10%)--one of a soft tissue metastasis, and two of local disease, with
      13 patients disease stabilizing for up to 20 months. The overall median survival
      was 13 weeks. Adverse events included hyperpigmentation, eczematous skin rashes
      and palpitations. CONCLUSIONS: Although only three patients had an objective
      response (10%), the 13 patients with stable disease for up to 20 months, and an
      overall median survival of 13 weeks, suggest that clofazimine, or other
      riminophenazine compounds may prove to be of value in hepatocellular carcinoma.

PMID- 9553670
TI  - Cytosine arabinoside, etoposide and aclarubicin (AVA) for the treatment of acute
      myeloid leukemia (AML) in elderly patients.
AB  - BACKGROUND: Elderly patients (age > or = 60 years) with acute myeloid leukemia
      (AML) have unfavourable prognoses when polychemotherapy regimens are used,
      because therapy response is characterized by low remission rates, short remission
      duration and high toxicity. PATIENTS AND METHODS: A phase II trial in elderly AML
      patients was conducted to determine the efficacy of two induction courses of a
      moderately-dosed combination of aclarubicin (25 mg/m2, 30 min i.v., days 1-4),
      etoposide (100 mg/m2, 30 min i.v., days 1-3) and conventional-dose cytosine
      arabinoside (ara-C, 100 mg/m2, c.i.v., days 1-3 and 30 min i.v., q 12 hours, days
      4-7) (AVA-7), followed by one consolidation treatment using a reduced-dose
      schedule over five days (AVA-5) after three months in CR. RESULTS: Thirty-two AML
      patients with a median age of 66.2 years (range 60-76) were included in the
      study: three of them had histories of preexisting myelodysplasia and one of
      polycythemia vera. Following 1-2 courses of AVA-7 17 patients (53%) achieved CR,
      two PR (6%), and nine had resistant disease (28%); the overall response rate was
      thus 59%. Toxicity was significant but acceptable, with an overall treatment
      related death rate of five of 32 patients (16%) after 63 courses of AVA. The
      median disease-free survival (DFS) was 12 months, and the median survival of all
      patients was 16.6 months. CONCLUSIONS: These results indicate that the
      combination of aclarubicin, etoposide and conventional-dose ara-C is effective in
      elderly AML patients. The relatively brief remission duration requires new
      consolidation and maintenance therapy approaches.

PMID- 9553671
TI  - Vinorelbine, bleomycin and methotrexate as a salvage therapy for patients with
      head and neck squamous carcinoma in relapse after cisplatin/fluorouracil.
AB  - BACKGROUND: Cisplatin (CDDP) and 5-fluorouracil (5-FU) represent the standard
      chemotherapy for advanced/recurrent head and neck squamous carcinoma (HNSC);
      however, the duration of response is often short, with a median survival of only
      five to six months. PATIENTS AND METHODS: Patients with HNSC were treated with
      vinorelbine 20 mg/m2 and methotrexate 50 mg/m2 every week and bleomycin 15 mg/m2
      every two weeks. All patients were previously treated with a CDDP/5-FU regimen.
      RESULTS: Forty-eight patients were evaluable for response and toxicity. After a
      median follow-up of 15 months, 16 patients are still alive and 32 have died. We
      had one complete response (2%), 12 partial responses (25%) (overall response rate
      27%; 95% CI: 14%-39%), 11 stabilizations (23%) and 24 progressions (50%) of
      disease. Neutropenia grade 3-4 was seen in 12 patients; peripheral neurotoxicity
      in two patients. There were no toxic deaths. CONCLUSIONS: This regimen,
      administered in an outpatient setting, revealed some activity as a second-line
      treatment in patients with HNSC, with acceptable toxicity.

PMID- 9553672
TI  - Consolidation therapy for advanced ovarian cancer.

PMID- 9553673
TI  - 5-Fluorouracil and mitomycin-C in colorectal cancer: unacceptable conclusion.

PMID- 9553674
TI  - Onycholysis in patients treated with docetaxel.

PMID- 9553675
TI  - [Leukotriene receptor antagonists and bronchial asthma].
AB  - Leukotrienes play an important role in the pathogenesis of the allergic bronchial
      asthma. The cysteinyl-leukotrienes C4, D4 and E4 (formerly known as slow reacting
      substance of anaphylaxis, SRS-A) are able to induce all components of the
      asthmatic reaction. The synthesis of adequate receptor antagonists stimulated
      expectations to develop on this way new and especially effective antiasthmatic
      drugs. The results of the first generation was disappointing. Newer compounds are
      able to protect from bronchoconstriction-inducing noxes (especially in analgesic
      intolerance), to improve chronic asthma (symptoms scores, long-time resp. rescue
      medication). Especially remarkable are recent data which prove antiinflammatory
      activities. Studies are underway to define the position of these drugs in
      generally accepted recommendations on asthma therapy. This group of drugs is the
      first one with a defined action.

PMID- 9553676
TI  - Characterisation of furoxancarbonitriles as a new class of vasodilators.
AB  - The synthesis, structural characterization, NO-donor properties, and in vitro
      vasodilating activities of a series of furoxancarbonitriles 2, 17-22a, b are
      reported. Some derivatives (2b, 2a, 18b, 21b, 22b) are more potent vasodilating
      agents than sodium nitroprusside (SNP), the reference compound, some others
      display similar potency (17b, 19b, 20b). Log EC50 values fit well on the linear
      correlation log EC50 versus log C0.1(1 min) (namely the logarithm of the
      concentration able to release 2.6 mumol l-1 min-1 of NO) found in a previous
      work. The haemodynamic profile in anaesthetised pigs for some selected
      derivatives (2a, b, 19a, b) is also presented. These profiles are consistent with
      that known for another furoxan NO-donor (4-hydroxymethyl-3-furoxancarboxamide,
      CAS 1609) and suggest similar characteristic of in vivo NO-release.

PMID- 9553677
TI  - Cardiovascular effects of (2RS,3SR)- 2-aminomethyl-2,3,7,8-tetrahydro-2,3,5,8,8
      pentamethyl-6H-furo- [2,3-e]indol-7-one hydrochloride (UK-1745), a novel
      cardiotonic agent with vasodilatory and antiarrhythmic properties.
AB  - The cardiovascular effects of (2RS,3SR)-2-aminomethyl-2,3,7,8- tetrahydro
      2,3,5,8,8-pentamethyl-6H-furo[2,3-e]indol-7-one hydrochloride (CAS 170684-14-7,
      UK-1745), a novel cardiotonic agent, were investigated using in vitro and in vivo
      preparations. In paced left atria isolated from guinea pigs, both UK-1745 and
      vesnarinone (CAS 81840-15-5) showed a concentration-dependent positive inotropic
      effect. In spontaneously beating guinea pig right atria, both agents caused only
      a minimal chronotropic effect. In isolated, blood-perfused canine papillary
      muscle preparations, UK-1745 and vesnarinone injected intra-arterially into the
      anterior septal artery (ASA) increased the developed tension in a dose-dependent
      manner. In isolated, blood-perfused canine sinoatrial node preparations, both
      agents injected into the right coronary artery (RCA) did not cause any
      appreciable changes in the sinus rate. UK-1745 increased the blood flow through
      the ASA and the RCA in a dose-dependent manner, whereas vesnarinone did not. In
      anesthetized open-chest dogs, UK-1745 injected intravenously increased cardiac
      contractility and cardiac output, and decreased left ventricular end-diastolic
      pressure, systemic vascular resistance and heart rate. In experimentally induced
      acute heart failure in anesthetized open-chest dogs, intravenously injected UK
      1745 effectively improved hemodynamic functions. In conscious instrumented dogs,
      orally administered UK-1745 increased LV dP/dtmax with insignificant changes in
      systemic blood pressure and heart rate. In mice, orally administered UK-1745
      protected the development of ventricular fibrillation induced by chloroform
      inhalation, whereas vesnarinone did not. Thus, in respect of inotropic and
      chronotropic effects, UK-1745 closely resembled vesnarinone, but differed from
      vesnarinone in respect of coronary vasodilating and antiarrhythmic effects. The
      results suggest that UK-1745 is a novel positive inotropic agent with
      vasodilatory and antiarrhythmic properties, without significant chronotropic
      action, and may be beneficial for the treatment of congestive heart failure.

PMID- 9553678
TI  - In vivo cardiotonic activity of aryl- and pyridyl-substituted fused imidazoles.
AB  - Two new imidazo[2,1-b]thiazoles related to sulmazole were synthesized and
      subjected to an in vivo cardiotonic assay with 14 analog compounds which gave the
      best results in previously reported in vitro tests. The data obtained show that
      three substituents (3-pyridyl, 4-pyridyl and 2,5-dimethoxyphenyl group) are
      useful pharmacophoric groups in modulating the in vivo cardiotonic activity of
      the fused imidazoles considered.

PMID- 9553679
TI  - Inhibitory action of silibinin on low density lipoprotein oxidation.
AB  - Low density lipoprotein (LDL) oxidation and smooth muscle cell growth represent
      key events in atherogenesis. Any mean to reduce these two phenomena may decrease
      the risk of coronary artery disease and atherosclerosis in general. The effects
      of silibinin (CAS 22888-70-6) on LDL oxidation and proliferation of vascular
      smooth muscle cells were evaluated in vitro. Silibinin (50-200 mumol/l) prolonged
      the lag times of both LDL autooxidation and oxidation by copper by > 50%, as
      assessed by recordings of diene formation. However, silibinin (up to 500 mumol/l)
      did not interfere with LDL-stimulated radiolabeled thymidine incorporation. These
      findings indicate that silibinin, apart from its hepatoprotective effects, has
      inhibitory properties on LDL oxidation in vitro. Therefore silibinin might
      represent a novel tool in the prevention and therapy of atherosclerosis.

PMID- 9553680
TI  - [Antihypertensive action of various talinolol dosages after four week's treatment
      in comparison with placebo].
AB  - The dose dependence of the antihypertensive effect of the beta 1 selective
      blocker talinolol (CAS 57460-41-0, Cordanum) was investigated in 97 essential
      hypertensive patients (mild to moderate) using the ambulatory blood pressure
      monitoring (ABPM) in a single-centre, double-blind, randomized parallel-group
      study. After 4 weeks of treatment a comparison was made between the once daily
      administered doses of 50, 100 and 200 mg as well as with placebo. The primary
      parameter was the mean diastolic blood pressure between 8.00 and 22.00 (dTMW).
      Furthermore, the duration of action of the once daily administration of 200 mg
      talinolol was compared with the twice daily application of 100 mg each. With
      regard to dTMW an increasing antihypertensive effect was determined for the
      dosage step from 50 mg to 100 mg talinolol/d. No further increase in the blood
      pressure lowering effect was observed with 200 mg talinolol/d. The highest
      frequency of therapy responders was found in the 100 mg group with 72.2%.
      Moreover it could be demonstrated, that within the dosage range of 1 x 100-200 mg
      Talinolol/d a significant and 24 h lasting reduction of blood pressure and pulse
      rate was achieved, including the early morning period. There were no differences
      between the blood pressure profile of the 200 mg group and the 2 x 100 mg group
      at the end of the 4 weeks treatment. All talinolol dosages investigated in this
      study were proved to be safe and well tolerated. The observed complaints
      classified as adverse drug reactions represented typical side effects of beta
      blockers of mild to moderate intensity. It can be concluded from the results that
      the once daily intake of talinolol in the dosage range of 100-200 mg/d shows a
      reliable efficacy in the treatment of essential hypertension accompanied by a
      noncritical safety profile.

PMID- 9553681
TI  - Effects of the novel oral antidiabetic agent HQL-975 on glucose and lipid
      metabolism in diabetic db/db mice.
AB  - The antidiabetic effects of 3-?4-[2-(5-methyl-2-phenyl-oxazol-4-
      yl)ethoxy]phenyl?-2S-propylamino-propionic acid (CAS 185679-16-7, HQL-975), a
      novel oral agent, on a genetically obese non-insulin-dependent diabetes mellitus
      (NIDDM) model (db/db mice) were examined. HQL-975 administration (3.7-34.1
      mg/kg/d for 7 days) decreased the levels of plasma glucose, triglyceride, total
      cholesterol, non-esterified fatty acid and insulin in the mice. In an
      intraperitoneal glucose tolerance test (IPGTT), HQL-975 administration decreased
      the fasting plasma glucose level and improved the glucose tolerance in the mice.
      The HQL-975 administration also significantly increased the glycogenesis and
      lipogenesis from 14C-glucose in liver, but did not alter the glycogenesis in the
      diaphragm or the lipogenesis in adipose tissues at 2 h after the glucose loading.
      In the HQL-975-treated db/db mice, the radioactivity of 14C-glucose incorporated
      into hepatic glycogen was higher than that incorporated into hepatic total
      lipids. After the administration of HQL-975 (34.1 mg/kg/d for 7 days) to db/db
      mice, the hepatic hexokinase and fatty acid synthetase activities were
      significantly increased, the glycogen synthase I activity was increased but not
      significantly, and the glucose-6-phosphatase and the phosphoenolpyruvate
      carboxykinase activities were decreased. These results suggest that HQL-975
      increases the hepatic glucose utilization and decreases the hepatic glucose
      production. Since hepatic glycogenesis is regulated by glucose itself but not by
      insulin in normoglycemic ICR mice, HQL-975 is thought to enhance the effect of
      glucose on the stimulation of hepatic glycogenesis. It is concluded that the
      enhancement of the hepatic glucose utilization played an important role in the
      hypoglycemic action of HQL-975.

PMID- 9553682
TI  - Comparison of the effects of ularitide acetate and other bronchorelaxing
      substances on the thrombin-induced permeability raise of human endothelial cell
      monolayers.
AB  - Endothelial cell contraction plays a pivotal role in vascular leakage. It
      increases the extravasation of fluid and macromolecules from the lumen into the
      interstitium. This is also true for bronchial edema. Previous studies have
      indicated that an elevation of intracellular adenosine-3',5'-cyclic monophosphate
      (cAMP) or guanosine-3',5'-cyclic monophosphate (cGMP), respectively, can
      counteract this vascular leakage by improving the endothelial barrier function in
      analogy to the relaxation of smooth muscle cells. To investigate the potential
      antiedemateous effects of ularitide acetate (CAS 115966-23-9), isoproterenol
      hemisulfate (CAS 6078-56-4), sodium nitroprusside (CAS 13755-38-9, SNP),
      aminophylline (CAS 317-34-0), and combinations of these compounds, their effects
      on thrombin-induced macromolecular permeability raise in relation to cGMP- or
      cAMP-levels, respectively, in a model of human umbilical vein endothelial cells
      (HUVECs) were examined. Ularitide acetate, isoproterenol hemisulfate, and SNP all
      increased the amount of cyclic nucleotides and decreased the raise in
      permeability in the following order of potency: isoproterenol hemisulfate >
      ularitide acetate > SNP. Aminophylline raised both cGMP- and cAMP-levels in a
      weaker amount and was not able to decrease the thrombin-induced permeability
      raise on its own. By way of contrast, preincubation of HUVECs with aminophylline
      resulted in a more than additive potentiation of the cGMP-levels and the
      permeability lowering induced by ularitide-acetate. These in vitro-data indicate
      that ularitide-acetate, especially in combination with phosphodiesterase (PDE)
      inhibitors, could probably have beneficial effects in bronchial permeability
      edema.

PMID- 9553683
TI  - Single dose study of the bioequivalence of two sustained-release theophylline
      formulations.
AB  - The relative bioavailability of theophylline (CAS 58-55-9) was evaluated after a
      single dose administration of two sustained-release theophylline tablet
      formulations: Controfilina-200 as test preparation (test) and a commonly used
      reference preparation (reference). The design of the study was crossover in
      twelve healthy volunteers, with a series of two experimental sessions. The two
      sessions were carried out at weekly intervals. Theophylline concentrations were
      measured by HPLC (high performance liquid chromatography). The bioavailability
      was compared using the parameters: AUC0-infinity (area under the concentration
      time curve), Cmax (maximal theophylline concentration), tmax (time after drug
      intake at which the maximal concentration is reached) and Cmax/AUC0-infinity. The
      results of this study indicated that the new generic sustained-release tablet and
      the reference are bioequivalent when the same dosage is administered.

PMID- 9553684
TI  - Synthesis of some new aroyl/aryloxy-2-amino-1,3-thiazole derivatives with anti
      inflammatory activity.
AB  - The synthesis of some novel aroyl/aryloxy aminothiazoles from the appropriate
      gamma-chloro-butyrophenones, gamma-chloro-butyrothienones, gamma-chloro
      aryloxypropanes with the corresponding substituted 2-amino-1,3-thiazoles is
      described. The spectroscopical data (UV, IR, 1H-NMR and MS) of the derivatives
      are presented.

PMID- 9553685
TI  - Disposition of a new nonsteroidal anti-inflammatory agent, S-2-[4-(3-methyl-2
      thienyl)phenyl]propionic acid, in rats, dogs and monkeys.
AB  - The disposition of S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (CAS 155680
      07-2, S-MTPPA, code: M-5011) was studied after oral administration to rats, dogs
      and monkeys using the 14C-labeled drug. After oral dosing, S-MTPPA was well
      absorbed from the gastrointestinal tract, to the extent of 97.7% in rats. The
      concentration of S-MTPPA in rat plasma reached a peak (Cmax: 13.07 micrograms/ml)
      at 15 min (tmax) after dosing and declined with a half-life (t1/2) of 2.5 h. The
      values of the parameters tmax, Cmax and t1/2 for dogs were 30 min, 26.2
      micrograms/ml and 7.0 h, and those for monkeys were 15 min, 12.8 micrograms/ml
      and 3.0 h, respectively. The radioactivity was widely distributed in tissues and
      almost completely excreted in urine and feces within 48 h after oral
      administration to rats. The excretion of radioactivity in bile, urine and feces
      within 48 h after oral administration of 14C-S-MTPPA to bile duct-cannulated rats
      amounted to 75.0, 18.6 and 1.4% of the dose, respectively. The drug was
      metabolized mainly by oxidation of the thiophenyl moiety and by glucuronidation
      of the carboxyl group in rats and monkeys. The major urinary and fecal metabolite
      in dogs was identified as the taurine conjugate of MTPPA.

PMID- 9553686
TI  - Pharmacokinetics of estradiol and of estrone during application of a new 7-day
      estradiol transdermal patch with active matrix.
AB  - The pharmacokinetic patterns of estradiol (CAS 50-28-2) and of estrone (CAS 53-16
      7) were investigated in 18 women in natural or surgical menopause during the
      application of a new estradiol transdermal patch with active matrix and without
      absorption enhancers designed for epicutaneous applications of 7 days
      (hereinafter called "patch 7D"). The study was made with randomized and balanced
      sequences of applications in cross-over of either patch 7D or of an authorized
      estradiol transdermal patch with a nominal release rate of 50 micrograms/day
      estradiol designed for a twice-a-week epicutaneous application (hereinafter
      called "patch 50"). The sequences consisted of applications for 3 weeks either of
      3 patches 7D or of 6 patches 50. The patches were applied on the skin of the hips
      or upper buttocks. The serum samples were obtained during the 1st and during the
      last week of application of the patches. Estradiol (E2) was assayed in serum by a
      double-antibody RIA method selective for free estradiol. Estrone (E1) was assayed
      in serum using a 3H-estrone RIA method. The steady state with regard to E2 and E1
      was achieved already during the application of the 2nd patch. Patch 7D provided
      within 6 h an increase of the E2 concentrations in serum from the basal
      postmenopausal level of less than 3 pg/ml to therapeutically effective
      concentrations. The Cmax of E2 of 45 pg/ml was reached on average after 25 h, the
      concentrations of E2 remaining at sustained and therapeutically effective levels
      during the whole application of patch 7D. At steady state, during the 3rd week of
      application, the Cav was on average 31 pg/ml. With a small delay, E1 also
      increased from the basal 15 pg/ml to a Cmax of 41 pg/ml after 44 h. At steady
      state, during the 3rd week of application, the Cav was on average 38 pg/ml. Patch
      7D provided a similar bioavailability as patch 50 with regard to the rate and the
      extent of absorption of E2, as shown by the AUCs during the 7-day applications of
      one patch 7D compared to those during the 7-day applications of 2 patches 50. The
      release of E2 from patch 7D is therefore similar to that of patch 50, i.e. on an
      average of 50 micrograms/day over a 7-day period of application. The E2/E1 ratio
      increased from the postmenopausal values lower than 0.2 found before the
      application of patch 7D to average values of 0.67, i.e., to values that are
      normally found during the fertile life of the woman. The improvement of the E2/E1
      ratio occurred already in the first 6-12 h of application of patch 7D. The E2/E1
      ratio returned rapidly to the initial low postmenopausal levels after removal of
      the patch. Patch 7D was well tolerated by the skin, probably because it does not
      contain absorption enhancers. It provoked, however, some systemic adverse
      reactions typical of E2 overdosing. In the therapeutic practice these adverse
      reactions can easily be avoided using patches 7D of lower strength. No drop-out
      due to systemic or local intolerance occurred. The adhesion of patch 7D on the
      skin was good. During the application of a total of 54 patches, only in one
      occasion one patch became partially detached (about 40% of the total area) from
      the 3rd to the 7th day during the first 7-day period of application.

PMID- 9553687
TI  - "Resultant bond moment" as a newly developed electronic parameter in the design
      of antibacterial, antiprotozoal nitroimidazole derivatives.
AB  - Nineteen nitroimidazole derivatives have been reported to be effective
      antibacterial against one strain each of Bacteroides fragilis and Clostridium
      perfringens. The negative logarithms of minimum inhibitory concentrations (MICs)
      of these nitroimidazoles were fitted by a biostatistical relation involving a
      newly designed structural descriptor, the Resultant Bond Moment (RBM). RBM was
      developed on the basis of the chemical attribute of bond moments of heteroatoms.
      RBM reflects the electronic characteristic of the molecule. Apart from this,
      steric, electronic, and hydrophobic parameters were also utilised in the search
      of a best fit regression equation. On the basis of these equations new
      investigative nitroimidazole derivatives have been predicted concerning their
      antibacterial and antiprotozoal efficacy.

PMID- 9553688
TI  - Antibacterial activity of rhodium, iridium, and ruthenium tripodal phosphine
      complexes.
AB  - Twenty-eight rhodium, iridium, or ruthenium complexes were evaluated for their in
      vitro antibacterial activity against Enterococcus faecalis ATCC 29212,
      Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922 and Pseudomonaa
      aeruginosa ATCC 27853. Ten compounds showed an antibacterial activity against
      Enterococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 29213 with a
      range of the minimum inhibitory concentrations (MICs) between 16 and 125
      micrograms/ml. None of the compounds exhibited antimicrobial activity against the
      gram-negative strains E. coli ATCC 25922 or Pseudomonas aeruginosa ATCC 29213
      with a concentration range between 4 and 500 micrograms/ml.

PMID- 9553689
TI  - Epoxyethane-/ethynesulfonamides with antifilarial activities. Degradation
      kinetics and inhibitory effect on filarial malate dehydrogenase and lactate
      dehydrogenase.
AB  - Some epoxyethane-/ethynesulfonamides had shown strong filaricidal activity with
      inconstant reproducibility as a result of a lack of stability in aqueous
      solution. The degradation in hydroxylic and aprotic solutions of two
      epoxyethanesulfonamides and one ethynesulfonamide was investigated using TLC,
      HPLC, GC and mass spectrometry. For both epoxydes, the degradation rate followed
      first-order kinetics and was more rapid in hydroxylic than in aprotic solutions.
      The degradation increased with the temperature whereas it was not modified with
      and without light exposure. Four kinds of degradation products were found: the
      first one involved the oxidation of the epoxyde bond, the second the breaking of
      the N-S bond, the third a desulfonation product and the fourth was not
      identified. In contrast, the stability of ethynesulfonamide was better than those
      of epoxyethanesulfonamide. These results suggest that epoxyethanesulfonamides
      should be kept at +4 degrees C before being injected to animals during the study
      of biological activity. Since epoxyde compounds are known to have inhibitory
      effects on parasite energy metabolism enzymes, the compunds were evaluated on two
      major filarial enzymes: lactate dehydrogenase (LDH) and cytoplasmic malate
      dehydrogenase (MDH). Both epoxyethanesulfonamides showed only a slight inhibitory
      effect on filarial LDH and MDH confirming the evidence that the main mode of
      action of these compounds remains to discover. Moreover, ethynesulfonamide and
      the degradation products of both epoxyethane-sulfonamides had no effect on LDH
      and MDH.

PMID- 9553690
TI  - Toxicities of 166Holmium-chitosan in mice.
AB  - 166Holmium (166Ho) is a radionuclide of rare earth chemical and is known to have
      antitumor activity. Several chemicals were complexed with 166Ho to facilitate the
      transport of this radionuclide to the site of action. In this study, 166Ho was
      complexed to chitosan (Chit) which decreases the distribution of Ho into other
      tissues when applied intrahepatically. To investigate the single dose toxicity,
      mice were administered intravenously with 1 mCi/kg body weight of 166Ho-Chit (DW
      166HC), Chit or nothing. Organ weights, hematological and histopathological
      studies were performed in 6 animals per group at 1, 3 and 14 days after
      administration. In 166Ho-Chit treated animals, a slight decrease of erythrocyte
      number was observed at day 14 and increases of relative liver and lung weights
      were found at day 3. Although marked multiple necrotic foci in the white pulp and
      depletion of marginal zone in the spleen were noted at day 1, these findings were
      decreased in severity and fully recovered at day 3 and day 14, respectively.
      Slightly decreased kidney weights were observed both in Chit and in 166Ho-Chit
      treated groups without histological alterations. Thus it is suggested that most
      effects of 166Ho-Chit observed at an early stage after administration are limited
      to rapidly dividing cells and reversible within 14 days.

PMID- 9553691
TI  - Antiviral potential of interferon-omega on hepatitis B virus replication in human
      hepatoma cells.
AB  - Interferon-alpha (IFN-alpha) and other cytokines are able to interfere with
      hepatitis B virus (HBV) replication. However, a sustained antiviral effect is
      achieved only in 25% to 40% of the patients with chronic HBV infection and
      clearance of the virus rarely occurs, stressing the need for developing
      therapeutic alternatives. In this study the antiviral potential of a new
      recombinant interferon, IFN-omega was investigated. IFN-omega was assessed in
      comparison with IFN-alpha 2c, IFN-gamma, and TNF-alpha with respect to production
      of HBV proteins and DNA in HepG2.2.15 cells, a HBV-DNA transfected hepatoma cell
      line which produces infectious viral particles. Cells were seeded at different
      states of confluence (20%-90%) and treated with increasing concentrations of
      interferons (5 to 5,000 U/ml), TNF-alpha (5 to 500 ng/ml), or combinations of
      both for one to three days. IFN-omega reduced the production of HBsAg down to 59%
      of the untreated controls, which was comparable to the reduction obtained by
      treatment with IFN-alpha (60%), the standard interferon used for the treatment of
      chronic HBV infections. The strongest inhibition, however, was achieved by
      treatment with 500 ng/ml TNF-alpha (42%). Likewise, production of HBeAg and
      synthesis of HBV DNA were inhibited to similar degrees by the different
      interferons. In non-replicating high-density cultures only TNF-alpha was
      effective. IFN-omega is of similar antiviral potential as IFN-alpha in this in
      vitro experimental system.

PMID- 9553692
TI  - Central trigeminal and posterior eighth nerve projections in the turtle Chrysemys
      picta studied in vitro.
AB  - Recent electrophysiological studies in the turtle Chrysemys picta have suggested
      that a neural correlate of the eye-blink reflex can be evoked in an in vitro
      brain-stem-cerebellum preparation by electrical rather than natural stimulation
      of the cranial nerves. Discharge recorded in the abducens nerve, which is similar
      to EMG recordings from extraocular muscles during eye retraction, is triggered by
      a brief electrical stimulus applied to the ipsilateral trigeminal nerve. Evidence
      also suggests that pairing a one-second electrical stimulus applied to the
      posterior eighth nerve immediately prior to a single shock to the trigeminal
      nerve results in classically conditioned abducens nerve discharge in response to
      the previously neutral eighth nerve stimulus. In view of these physiological
      findings, the aim of the present study was to examine the central projections of
      trigeminal and posterior eighth nerve inputs to elucidate the anatomical
      substrates that may underlie the in vitro eye-blink reflex and possible pathways
      involved in reflex conditioning. Neurobiotin (NB) or fluorescein dextran (FD) was
      pressure injected into the cut end of either the trigeminal or posterior eighth
      nerve of the in vitro brainstem-cerebellum. Following trigeminal nerve
      injections, both tracers showed label in the ipsilateral trigeminal nuclear
      complex. Direct projections to the ipsilateral principal and accessory abducens
      motor nuclei were observed, suggesting that the eye-blink reflex is monosynaptic.
      Trigeminal nerve axons were also observed to terminate in the ipsilateral
      cerebellar cortex. The results of the posterior eighth nerve injections showed
      axonal projections and terminals in the cochlear, vestibular and principal
      sensory trigeminal nuclei. Terminal label was also observed in the ipsilateral
      cerebellar cortex, deep cerebellar nuclei, and in the principal and accessory
      abducens motor nuclei. Results from the NB cases suggested transneuronal
      transport of this tracer substance, whereas the FD cases did not. The present
      findings suggest that convergence of trigeminal and posterior eighth nerve inputs
      occurs in the ipsilateral cerebellar cortex, the principal sensory trigeminal
      nucleus, and the principal and accessory abducens motor nuclei. These regions of
      convergence may therefore be considered as potential sites of synaptic
      modification during in vitro studies of the conditioned abducens nerve reflex.

PMID- 9553693
TI  - Afferent and efferent connections of nucleus praeeminentialis in the channel
      catfish: a reevaluation.
AB  - Nucleus praeeminentialis (nPr) is an isthmic nucleus that has been described in
      the brains of electrosensory teleost fishes and a single non-electrosensory
      species. The nucleus receives axon collaterals of ascending medullary sensory
      lemniscal neurons. Axons of nPr neurons project in turn back down onto those same
      populations of medullary projection neurons via a descending parallel fiber
      system (the molecular layer or cerebellar crest). Thus nPr forms a link in a
      sensory feedback loop that modulates the activity of neurons that relay
      information from medulla to midbrain. The purpose of this study is to investigate
      the nature of the afferent and efferent connections of the nPr with the specific
      aim of investigating other sources of input into this modulatory circuit.
      Transport of neuronal tracers (horseradish peroxidase, DiI and dextran amines)
      revealed that nPr has extensive interconnections with nuclei in the basal
      metencephalon, cerebellum, octavolateralis column and basal medulla. A previously
      described source of afference, the torus semicircularis in the mesencephalon, was
      not indicated by our studies. Our studies suggest that in addition to regulating
      the sensitivity and resolution of electrosensory and mechanosensory lateral line
      systems, the nPr may play a role in the resolution of signal ambiguities posed by
      auditory or vestibular stimulation of the saccular endorgan of the inner ear.

PMID- 9553694
TI  - Role of the archistriatal nucleus taeniae in the sexual behavior of male Japanese
      quail (Coturnix japonica): a comparison of function with the medial nucleus of
      the amygdala in mammals.
AB  - Nucleus taeniae (Tn) is a prominent cell group within the medial archistriatum of
      birds. Based upon similarities in sex-steroid binding sites, this nucleus has
      been hypothesized to be homologous to the medial nucleus of the amygdala (Me) in
      mammals, which is known to modulate the expression of sexual behavior in rodents.
      We therefore tested whether or not Tn likewise plays a role in the expression of
      sexual behavior in male Japanese quail. We found that bilateral damage to Tn
      produced deficits in several components of male responses toward female stimuli
      that were indicative of decreased sexual arousal, including goal-oriented
      responses, vocalizations associated with courtship, and motor reflexes that
      precede copulation. Our results suggest that Tn influences a wide range of
      behavioral functions in response to sexual stimuli, and they indicate a function
      for this nucleus similar to that subserved by the Me in mammals. These results
      strengthen the argument that these sex-steroid accumulating cell groups are
      homologous and suggest a conservation of function for them despite the vastly
      divergent evolutionary histories separating birds and mammals.

PMID- 9553695
TI  - A comparison of encephalization between odontocete cetaceans and anthropoid
      primates.
AB  - There have been very few studies of brain size and encephalization in cetaceans
      and essentially none that have made direct quantitative comparisons of cetaceans
      and another mammalian group using large normative samples. In the present study
      two different measures of encephalization were calculated and used to rank and
      compare 21 odontocete species and 60 anthropoid primate species. Comparisons were
      made both within and between the two groups. Results show that the
      encephalization level of Homo sapiens is still extraordinary relative to that of
      nonhuman species. Nevertheless, a subset of delphinid odontocetes are
      significantly more highly encephalized than the most highly encephalized
      anthropoid primates and narrow the gap in encephalization between humans and
      nonhumans substantially. These findings may have implications for comparative
      models of the relative importance of brain size versus brain organization for the
      evolution of intelligence.

PMID- 9553696
TI  - Giant cell tumor of bone.
AB  - Giant cell tumor of bone is an unusual neoplasm and treatment commonly leads to
      local recurrence. This can be related to the aggressiveness of the tumor or to
      the incompleteness of its removal. This study includes 27 cases that presented to
      our institution between the 1984 and 1994. One case was as a consultation only
      and 9 cases, either Campanacci Grade 3 or patients with considerable joint
      destruction, were treated by resection and reconstruction. One case was treated
      by curettage and cementation. Sixteen cases were treated with a combination of
      radical curettage, high speed burring, pulsatile lavage, and bone graft (either
      autograft or allograft mixed with autograft). No other adjuvant therapy was used.
      All of these 16 cases had a minimum follow-up of 5 years and none had a local
      recurrence. This study demonstrates that local control of giant cell tumors can
      be obtained by appropriate staging, resection of aggressive tumors, and by
      conservative management of the others. Such conservative management provides a
      bony matrix for the subchondral bone that is preferable to other treatments that
      have become popular in recent years, including cementation. This should provide
      better joint function in the longer term. High local recurrence rates have been
      reported in other series, but by a combination of appropriate selection of cases
      and by careful treatment of the Campanacci Grade 1 and 2 cases, these patients
      can have an uncomplicated outcome.

PMID- 9553697
TI  - Outcomes following treatment of metastatic spine tumors.
AB  - Fifty seven consecutive patients with metastatic spine tumors were assessed for
      their suitability for operative treatment or radiotherapy and/or chemotherapy
      using a modified version of the Nihon University scoring system. Using this
      scoring system 29 patients underwent surgery and 28 received
      radiotherapy/chemotherapy. The outcomes were assessed to determine if a modified
      scoring had any effect on patient survival. No statistical difference was found
      between the two groups, though a trend was noted--the group receiving surgery had
      a mean survival of 30 weeks compared to a mean survival of 16 weeks found in the
      non-surgical group.

PMID- 9553698
TI  - The surgical management of degenerative lumbar scoliosis. Posterior
      instrumentation alone versus two stage surgery.
AB  - Twenty-one patients who underwent surgery for degenerative scoliosis were
      retrospectively reviewed. Eleven patients underwent staged anterior and posterior
      surgery. Ten patients had a single posterior procedure. Posterior instrumentation
      to the sacrum was done in all cases. Average length of follow-up was 3.8 years
      (range: 2 to 7 years). All patients were assessed by the Oswestry Disability
      Questionnaire and Low-Back Outcome Score. Additional questions included analogue
      scales for pain and quality of life, and self-rating of the outcome of treatment.
      Nine patients that had two stage surgery and 4 patients that had single posterior
      surgery considered their outcome to be good or excellent (p = 0.13). This
      correlated with better functional tolerance, specifically sleep, lifting,
      sitting, and social life. Although pain intensity was the same for both groups,
      only the staged group reported significant reduction in analgesic intake.
      Significant correction in scoliosis and the lumbosacral fractional curve was
      noted only following staged surgery. A solid spinal fusion determined a
      satisfactory outcome irrespective of the method of treatment. Staged anterior and
      posterior surgery for degenerative lumbar scoliosis resulted in a better fusion
      rate, greater correction of deformity, and more improvement in function than did
      posterior surgery alone.

PMID- 9553699
TI  - Cytokines and matrix metalloproteinases mRNA expression in archival human tissues
      from failed total hip arthroplasty using in situ hybridization and color video
      image analysis.
AB  - Reports on the histological and biochemical nature of periprosthetic
      fibrous/granulomatous tissue has, to date, been largely limited to frozen tissue
      sections. This study reports the cytokine and matrix metalloproteinase profiles
      found in periprosthetic interface tissues in THA which have failed due to aseptic
      loosening and in capsular tissues obtained at primary surgery. The study employs
      immunohistochemistry, in situ hybridization, and color video image analysis on
      formalin fixed and paraffin embedded sections.

PMID- 9553700
TI  - A quantitative analysis of knee joint kinematics during the sidestep cutting
      maneuver. Implications for non-contact anterior cruciate ligament injury.
AB  - This study accurately quantifies the knee joint kinematics associated with
      sidestep cutting maneuvers in vivo. These data were subsequently evaluated to
      determine the relationship between sidestep cutting and non-contact anterior
      cruciate ligament (ACL) injury. Sixteen male subjects, proficient in the sidestep
      cutting maneuver, had knee joint kinematic data recorded during the stance phase
      of straight line running and sidestep cutting. Cutting speeds (5.5 msec-1 to 7.0
      msec-1) and angles (30 degrees to 55 degrees) were chosen to reflect the sporting
      context. All subjects underwent medical screening prior to testing to ensure data
      represented joint biomechanics of healthy, ACL intact individuals. The temporal
      three dimensional positions of externally mounted (skin) markers were submitted
      to a custom software package (JTMOTION), which described in clinically meaningful
      terms, movements for the three rotational degrees of freedom at the knee joint.
      While mean patterns of motion for the three clinical knee rotations compared
      favorably between running and cutting data, sidestepping induced significantly (p
      < 0.01) greater maximum knee joint rotations during stance. Knee joint rotational
      ranges were also found to be significantly (p < 0.01) larger during cutting when
      compared to running. Increases in knee joint kinematics during cutting however,
      were not of a great enough magnitude to alone elicit spontaneous non-contact ACL
      injury, falling well within "safe" ranges of knee motion. Significant increases
      in inter-trial variability for the three rotations were observed in some subjects
      for sidestepping compared to running. It was concluded that a lack of consistency
      in knee joint biomechanics between cutting maneuvers increased the risk of ACL
      injury with the performance of an abnormal and potentially hazardous sidestep
      being more likely. The risk of non-contact ACL injury during cutting maneuvers
      was suggested to increase further when an individual displayed these "atypical"
      joint biomechanics in conjunction with specific joint structures, levels of
      experience and conditioning, and ligament morphologies.

PMID- 9553701
TI  - The current state of bone and tissue banking in Australia.
AB  - The development of bone and tissue banking in Australia over the last decade is
      described and details of the administrative structure, donor and recipient
      testing protocols, allograft segment processing procedures, and internal audit
      safety arrangements are also provided. Demographic data concerning both the
      retrieval and dispersal of musculoskeletal allograft materials in Australia are
      also discussed. Current price schedules for a variety of allograft materials
      available in Australia are made available for international comparison.

PMID- 9553702
TI  - Orthopaedic education in Australia.

PMID- 9553703
TI  - Simultaneous bilateral total hip arthroplasty with hydroxyapatite coated
      implants.
AB  - Thirty patients (60 hips) who underwent simultaneous bilateral total hip
      arthroplasty with hydroxyapatite components were followed from 24 to 78 months
      (mean: 49 months). All patients showed improvement in postoperative hip score
      rating compared to preoperative for pain, function, and range of motion.
      Postoperative complications were minimal compared to other series. There were no
      thromboembolic complications. Heterotopic bone was noted in 18 hips (30%). At
      latest follow up no patients had radiographic evidence of component loosening.

PMID- 9553704
TI  - Reconstruction using implants compatible with MRI for malignant spine tumors.
AB  - It is necessary to resect malignant spine tumors aggressively and to subsequently
      reconstruct the spinal column. The Diapason screw and hook system, which is
      compatible with magnetic resonance imaging, has been used recently for
      reconstruction. This study included 17 patients (5 with primary tumors and 12
      with metastatic tumors) who underwent excision and reconstruction with the
      Diapason screw and hook system. The surgical procedures performed were circum
      spinal decompression by posterior extensive curettage in 12 cases, and en bloc
      total spondylectomy in 5. The follow-up periods ranged from 6 to 28 months.
      Though paralyses of Frankel grade B in 2 patients were not improved, paralyses of
      Frankel grade C in 10 cases and Frankel grade D in 4 cases improved to Frankel
      grade D or better postoperatively. MRI was performed to detect recurrences during
      the follow-up period. Recurrence of paralysis occurred in 5 patients. MRI could
      disclose recurrences of tumors in these patients because there were fewer signal
      loss artifacts in these implants than are found in those made of stainless steel
      alloy. For detecting recurrences, the Diapason system was satisfactory in the MRI
      follow-ups.

PMID- 9553706
TI  - A case-control study of verocytotoxigenic Escherichia coli infection in cats with
      diarrhea.
AB  - The objectives of this study were to determine the prevalence of enteric
      verocytotoxigenic E. coli (VTEC) infection in a population of cats in Ontario,
      and to determine whether an association exists between the presence of VTEC and
      feline diarrhea. Fecal samples from 179 cats, representing 113 cats with diarrhea
      and 66 cats with normal feces, were cultured for E. coli. The fecal cultures were
      screened for verocytotoxin activity with a Vero cell assay. Confirmation of the
      presence of verocytotoxin (VT) genes was done with polymerase chain reaction
      (PCR) amplification; the frequency of occurrence of the genes for generic VT,
      VT1, and VT2 was determined. VTEC-positive samples were defined as those that
      demonstrated cytotoxicity on the Vero cell assay and yielded E. coli possessing
      one or more of the VT genes. All VTEC-positive isolates were serotyped. The
      overall prevalence of enteric VTEC infection in the cats was 12.3% (22/179).
      Statistical analysis of the case-control data showed no significant association
      between VTEC infection and diarrheal illness. The majority of the cats with VT
      positive E. coli were positive for the presence of the generic VT, rather than
      for VT1 or VT2; it is therefore possible that a novel verocytotoxin gene may
      exist in E. coli isolated from cats. Eight VTEC strains were identified by
      serotyping; 4 of these serotypes have previously been isolated from humans, and 2
      from cattle, suggesting that cats may be capable of acting as reservoirs for
      human and bovine VTEC serotypes.

PMID- 9553705
TI  - Localization of potential binding sites for the edema disease verotoxin (VT2e) in
      pigs.
AB  - The purpose of this study was to identify organs and cells to which the edema
      disease verotoxin (VT2e) could bind in pigs. Frozen 4-5 microns thick sections of
      organs usually affected in edema disease (colon, spinal cord, cerebellum and
      eyelid) and organs not usually affected (liver, ileum) from two 5- to 6-week-old
      weaned pigs were permeabilized with acetone, then exposed to VT2e. Unbound VT2e
      was removed by washing and bound VT2e was detected by immunohistochemistry. In
      the eyelid, double-label immunofluorescence was used to identify the cells to
      which VT2e bound. VT2e was shown to bind to all six organs that were examined.
      The toxin bound to arteries in all organs, to veins in all organs except the
      liver, and to enterocytes in the ileal crypts. Double labelling of eyelid with
      monoclonal antibodies specific for von Willebrand factor or alpha-smooth actin
      and VT2e showed that the toxin bound to endothelial and vascular smooth muscle
      cells. The binding of VT2e to endothelium is consistent with findings for other
      verotoxins but binding to vascular smooth muscle has not been reported for other
      verotoxins. It is concluded that i) factors other than the presence of receptors
      for VT2e influence the development of lesions in edema disease, and ii) smooth
      muscle necrosis, which is characteristic of the vascular lesions in edema
      disease, may be due to a direct action of toxin on smooth muscle cells.

PMID- 9553707
TI  - Pathogenesis of porcine Actinobacillus pleuropneumonia: Part I. Effects of
      surface components of Actinobacillus pleuropneumoniae in vitro and in vivo.
AB  - To understand the role of non-secreted components of Actinobacillus
      pleuropneumoniae in virulence, we investigated in vitro cytotoxicity and in vivo
      pulmonary changes in pigs due to various A. pleuropneumoniae (serotype 1)
      fractions. Following 1.5 h incubation, lipopolysaccharide (LPS), 2 crude extracts
      and bacterial culture supernatant (BCS) at high concentrations were cytotoxic to
      porcine pulmonary alveolar macrophages (PAM), peripheral blood mononuclear
      leucocytes, neutrophils and a cultured porcine bone marrow cell line. Heat-killed
      bacteria were cytotoxic to PAM after 24 h incubation. The 2 crude extracts were
      prepared by shaking either intact bacteria after removing culture supernatants
      (crude surface extract, CSE), or whole bacterial culture (crude surface plus
      culture supernatant extract, CSSE) with glass beads in saline at 60 degrees C.
      Further experiments showed that proteins from the bacterial membrane were
      partially involved in cytotoxicities of these 2 extracts. Both BCS and CSSE
      caused multivocal hemorrhage and neutrophil infiltration when inoculated into
      porcine lungs, but CSE did not. The lung:whole body weight ratios of the pigs
      treated with CSSE were significantly higher (P < 0.05) than those of pigs treated
      with BCS, CSE, or control solution. It is concluded that beside the secreted
      proteins, bacterial surface components including LPS and non-secreted proteins
      were cytotoxic in vitro; and secreted and non-secreted components act
      synergistically to cause lung lesions.

PMID- 9553708
TI  - The immunological response of llamas (Lama glama) following experimental
      infection with Mycobacterium bovis.
AB  - Llamas were experimentally infected with Mycobacterium bovis in order to evaluate
      the axillary skin test and the ELISA as diagnostic procedures for tuberculosis in
      llamas (Lama glama). Six llamas were given a single intratracheal challenge with
      1 of 2 doses of a recent field isolate of M. bovis and 2 llamas were left as
      noninfected controls. This resulted in a progressive disease in some animals with
      1 mortality as early as 68 d post-infection (PI). The tuberculin skin test, at
      the axillary site, was positive in 4 of 5 infected llamas at 80 d PI. At 143 d
      PI, all 3 surviving lamas were positive, including the one which had not
      responded at 80 d PI. The application of skin and serological tests throughout
      the course of this experiment adds support for the need to further evaluate the
      skin test and its anamnestic effect on serodiagnosis since serological responses
      were generally not observed in the absence of skin testing or antibiotic
      treatment. The wide variation in M. bovis antigens recognized by the serological
      response would indicate that a diagnostic panel should include multiple antigens
      such as MPB70 and lipoarabinomannan (LAM). While skin testing or serology alone
      may be of limited value to diagnose tuberculosis in llamas, together they may
      offer an enhanced potential for immunodiagnosis of tuberculosis.

PMID- 9553709
TI  - Differentiation between porcine reproductive and respiratory syndrome virus
      isolates by restriction fragment length polymorphism of their ORFs 6 and 7 genes.
AB  - Three distinct antigenic profiles were identified by comparing the reactivities
      of 15 Canadian field isolates, the attenuated U.S. vaccine (Ingelvac MLV) strain
      and 2 European reference strains (Lelystad and Weybridge) of the porcine
      reproductive and respiratory syndrome virus (PRRSV) by indirect
      immunofluorescence with a set of 4 monoclonal antibodies to the nucleocapsid (N)
      protein and 2 other to the matrix (M) protein. In the present study, 9 Canadian
      isolates for which the sequences were determined appeared closely related to 2
      U.S. reference strains (ATCC VR-2332 and ATCC VR-2385) with amino acid identities
      varying between 90 to 98% for the M and N proteins; substitutions in the
      nucleotide sequences were distributed randomly throughout the ORFs 6 and 7 genes,
      and most were 3rd base silent mutations. In comparison, more than 30% divergence
      was demonstrated with the Lelystad virus. Furthermore, differentiation between
      North American and European isolates, and between field isolates and the MLV
      strain could be achieved by cutting PCR-amplified products encompassing both ORFs
      6 and 7 genes with 4 restriction endonucleases. When taken individually, BsaJI
      and AluI were the more appropriate restriction enzymes for distinguishing the
      vaccine strain from field isolates. The results obtained suggest that the
      restriction fragment length polymorphism of the genomic region covering the ORFs
      6 and 7 genes may be a valuable tool to differentiate among PRRSV isolates.

PMID- 9553710
TI  - A bovine mammary endothelial/epithelial cell culture model of the blood/milk
      barrier.
AB  - The complex nature of the mammary gland has hampered in-depth studies of the
      relationship of the circulatory system to cells lining the teat ducts and alveoli
      of the gland. This study reports an in vitro model of endothelial and epithelial
      cells separated by a subcellular matrix that simulates the blood milk barrier of
      the bovine mammary gland. Dual chamber culture dishes with a porous membrane
      separating the upper and lower chamber were used. Endothelial and epithelial
      cells were cultured on opposite sides of the porous membrane. A collagen and
      fibroblast subcellular matrix, separating the 2 cell layers, simulated the in
      vivo interstitial tissue. Changes in surface binding of anti-bodies to
      polymorphonuclear neutrophils (PMN) following their migration from the upper to
      the lower chamber simulated the passage of PMN from blood to milk. Changes in the
      binding of antibodies to PMN agreed with results observed following the migration
      of PMN from blood to milk in vivo. This gives credence to the model's potential
      value for studies where more direct observation of the blood/milk barrier is
      required. The model will be further tested for its usefulness as an assay for
      determining: 1) antibiotic diffusion from milk to blood and from blood to milk,
      2) cytotoxicity of prophylactic and therapeutic mammary infusion products, 3)
      factors affecting bacterial adhesion and penetration of mammary epithelial
      tissue, 4) effectiveness of antibodies present in lacteal secretions in
      preventing bacterial adhesion, and 5) the feasibility of gene constructs to
      induce synthesis and secretion of mastitis-preventing compounds and prophylactic
      and therapeutic compounds for treatment of human disorders.

PMID- 9553712
TI  - Purification of myeloperoxidase from equine polymorphonuclear leucocytes.
AB  - Increases of plasma concentrations of neutrophil myeloperoxidase (MPO) can be
      used as markers of polymorphonuclear leucocytes (PMN) activation in pathological
      situations (sepsis, acute lung injury, acute inflammation). To develop an assay
      for measurement of plasma MPO in horses during the above-mentioned infectious and
      inflammatory conditions, MPO was purified from equine PMN isolated from blood
      anticoagulated with citrate. PMN were extracted in a saline milieu (0.2 M Na
      acetate, 1 M NaCl, pH 4.7) to eliminate most of cellular proteins. Pellets were
      then extracted in the same buffer containing cationic detergent (1%
      cetyltrimethyl ammonium bromide). The supernatant was further purified by ion
      exchange chromatography (Hiload S Sepharose HP column 0.5 x 26 cm, equilibrated
      with 25 mM Na acetate, 0.2 M NaCl, pH 4.7) with a NaCl gradient (until 1 M). Most
      of the peroxidase activity of MPO (spectrophotometrically measured by the
      oxidation of orthodianisidine by hydrogen peroxide) was eluted at 0.65 M NaCl.
      MPO was further purified by gel filtration chromatography (Sephacryl S 200 column
      2.6 x 42 cm with 25 mM Na acetate, 0.2 M NaCl, pH 4.7). MPO (specific activity:
      74.3 U/mg) was obtained with a yield of 30% from the detergent extraction
      supernatant. Electrophoresis (non-reducing conditions) showed 3 bands identified,
      by comparison with human MPO, (i) the mature tetrameric enzyme (150 kDa) with 2
      light and 2 heavy subunits, (ii) the precursor form (88 kDa) and (iii) a form of
      the heavy subunit without the prosthetic heme group (40 kDa). The mature enzyme
      and its precursor were glycosylated and possessed peroxidase activity. Equine MPO
      showed strong similarities with human and bovine MPO, with an absorption peak at
      430 nm (Soret peak) characteristic of ferrimyeloperoxidase. Enzymatic activity
      was pH dependent (optimal value at pH 5.5).

PMID- 9553713
TI  - Evaluation of an in vitro degranulation challenge procedure for equine pulmonary
      mast cells.
AB  - Pulmonary mast cells (PMC) are important components of the inflammatory process
      in equine allergic lung diseases such as heaves. Very little, however, is known
      of the degranulation kinetics of these cells and thus, their pathophysiologic
      role remains largely speculative. The purpose of this study was to develop a
      repeatable protocol for in vitro equine PMC degranulation. Five mature horses
      (sex: 2 M, 3 F; age: 8.8 +/- 6.5 y), historically free of pulmonary disease and
      normal on clinical respiratory examination, arterial blood gas analysis,
      pulmonary mechanics testing and histamine inhalation challenge, were studied.
      Bronchoalveolar lavage was performed on 4 separate occasions, at least 2 d apart,
      in a different lung lobe on each occasion. The lavage fluid was concentrated by
      centrifugation. Cells were resuspended in modified HEPES/Tyrode, assessed for
      viability by Trypan blue exclusion, and PMC concentration determined. Cell
      inocula containing 30,000 PMC were incubated with 10(-8) to 6 x 10(-5) M A23187.
      Cells were then separated by centrifugation and histamine release (HR) was
      determined by fluorometric assay. The procedure was readily performed and yielded
      sufficient PMC for 30 to 60 inocula per lavage. Maximal HR (34.4 +/- 16.1%) was
      obtained with 10(-5) M A23187. The degranulation process was largely complete by
      20 min but cell lysis was negligible. The challenge was repeatable within horse
      and produced a mean coefficient of variability of 23.0% following 20 min
      incubation with 10(-5) M A23187. We conclude that equine PMC degranulation can be
      repeatably performed in vitro and speculate that this protocol may be useful in
      further studies on the pathophysiology and treatment of equine allergic lung
      diseases.

PMID- 9553711
TI  - Serum copper and ceruloplasmin activity at the early growing stage in foals.
AB  - Serum concentrations of copper (Cu), zinc (Zn), manganese (Mn), calcium (Ca) and
      inorganic phosphorus (P), as well as antigenic ceruloplasmin (Cp) and oxidase
      activity as a functional index for copper metabolism, were measured in 10 foals
      (5 males and 5 females) and their dams. Samples were harvested from the foals
      within 1 wk after birth and monthly from 1 to 17 mo of age. Samples were
      collected from their dams in the perinatal period (monthly from 2 mo before
      delivery to 5 mo postpartum). Serum oxidase activity, antigenic Cp and Cu in
      foals were extremely low at 1 wk. Serum Cp had the lowest value of 17.0 +/- 8.0
      (mean +/- SD) mg/dL within the 1st wk, then increased rapidly up to 43.7 +/- 5.8
      mg/dL at 1 mo, and maintained this level until the 17th mo. Serum Zn in foals had
      the highest value of 73.2 +/- 13.1 micrograms/dL within 1 wk, then decreased to
      38.3 +/- 5.9 micrograms/dL by 17 mo. Serum Mn, Ca and P in mares were almost
      stable and within established reference ranges for our laboratory in the
      perinatal period, and these values in foals were also in the normal range. Even
      on appropriate feeding, serum Cu, Cp and oxidase activity were quite low a few
      weeks after birth, while a higher proportion of Cp-binding copper was found in
      the foals. This might be caused by the limited synthesis of ceruloplasmin in this
      period. These data suggest that newborn foals are in a critical situation of
      marginal copper status in the early stage of growth.

PMID- 9553714
TI  - An evaluation of the clinical pathologic findings in experimentally induced
      urinary bladder rupture in pre-ruminant calves.
AB  - The purpose of this project was to study the biochemical abnormalities that
      develop over time in preruminant calves with experimentally induced
      uroperitoneum. Uroperitoneum was produced by incising the bladder via a standing
      left flank laparotomy. Serum and peritoneal concentrations sodium, chloride,
      potassium, phosphate and creatinine were determined at 0, 2, 4, 8, 24, and 40 h.
      Serum creatinine concentration was increased by 8 h post-bladder rupture.
      Peritoneal concentrations of potassium and phosphate were significantly elevated
      2 h after bladder rupture and peritoneal creatinine was significantly elevated by
      4 h. Serum to peritoneal fluid ratios for potassium, phosphate and creatinine
      exceeded 2:1 within 2 h of bladder rupture. Pre-ruminant calves with
      experimentally induced uroperitoneum did not become hyperkalemic during the 40 h
      experiment.

PMID- 9553715
TI  - An evaluation of protein/fat ratio in first DHI test milk for prediction of
      subsequent displaced abomasum in dairy cows.
AB  - First DHI test milk that was sampled prior to displaced abomasum (DA) diagnosis
      was used to evaluate milk protein/fat ratio (PFR) for prediction of subsequent DA
      in dairy cows. Odds ratio, sensitivity, specificity, and likelihood ratio were
      determined. Twenty-seven DA cases were matched to 3 controls per case by herd and
      calving date. Milk was tested at a median of 19 d after calving, which was 8 d
      prior to the median time of DA diagnosis. Adjusted for parity and days in milk, a
      protein/fat ratio < or = 0.72 was 8.2 times more likely to come from a cow
      subsequently diagnosed with DA than a protein/fat ratio > 0.72. Using the cut off
      value of 0.72, the sensitivity of PFR for DA was 80% and the specificity was 68%.
      A receiver operating characteristics curve indicated that the minimum sum of
      false negative and false positive results was at a PFR cut off value of 0.72. The
      likelihood ratio indicated that protein/fat ratios < or = 0.62 are 3.8 times more
      likely to come from cows that are diagnosed subsequently with DA than from cows
      without DA. The protein/fat ratio in 1st DHI test milk may predict subsequent DA
      in dairy cows.

PMID- 9553716
TI  - Molecular cloning and expression of the canine metallothionein-III gene.
AB  - We have isolated and determined the complete nucleotide sequence of canine
      metallothionein-III (MT-III) cDNA. The predicted amino acid sequence of the
      canine MT-III showed a high homology (93%, 87% identity) to that of human and
      mouse MT-III. The canine MT-III had 2 insertions relative to known mammalian MT-I
      and MT-II: a threonine after the 4th amino acid and a block of 6 amino acids near
      the carboxyl terminus. Expression of the canine MT-III mRNA was found exclusively
      in the central nervous system, where neurons in the olfactory bulb, hippocampus
      and cerebral cortex showed predominant signals.

PMID- 9553717
TI  - A monoclonal antibody-based immunoperoxidase monolayer (micro-isolation) assay
      for detection of type 1 and type 2 bovine viral diarrhea viruses.
AB  - A monoclonal antibody (mAb)-based immunoperoxidase monolayer assay (IPMA) for
      detection of bovine viral diarrhea virus (BVDV) was developed and compared with
      an existing bovine polyclonal antibody (pAb)-based IPMA. A pool of 5 mAbs, 4 mAbs
      produced to a type 1 BVDV and 1 mAb produced to a type 2 BVDV, was utilized in
      the mAb-IPMA. The mAbs were chosen for inclusion in the pool because of their
      broad cross-reactivities with type 1 and/or type 2 BVDV, their apparent avidities
      for antigen, their reactivity to different BVDV proteins, and their lack of
      competition for binding sites or their binding to unusual BVDV isolates. The mAb
      IPMA outperformed the pAb-IPMA in staining, ease of reading test results, and
      relative sensitivity with a panel of known BVDV positive and negative sera. The
      relative sensitivities of the mAb-IPMA and pAb-IPMA were 100% and 93.5%,
      respectively, for 62 positive samples including several that were known to
      contain type 2 BVDV. With retesting, the pAb-IPMA gave a similar level of
      sensitivity as that of the mAb-IPMA. Both tests gave a specificity of 100% for 40
      negative serum samples obtained from a BVDV-free herd.

PMID- 9553718
TI  - Expression of a 50 kDa putative receptor for bovine viral diarrhea virus in
      bovine fetal tissues.
AB  - The expression of a 50 kDa bovine viral diarrhea virus putative receptor in
      different bovine fetal tissues from 3-month old fetuses was studied. The receptor
      expression was examined by immunocytochemical staining and by immunoblotting
      using antiidiotypic probe (anti-D89). Intense specific staining in enterocytes of
      the small and large intestines, cortical tubular epithelial cells of kidneys,
      respiratory epithelial cells of the trachea and esophageal mucosal epithelial
      cells was observed, demonstrating the strong expression of bovine viral diarrhea
      virus receptor in the tissues. Weak staining was found in cerebellum, thymus,
      spleen, liver, cerebrum, and lung tissues; however, heart tissues were negative.
      Immunoblotting results correlated with the immunoperoxidase staining assays.
      Thus, the expression levels of the receptor are variable in different tissues.
      This pattern of expression may provide clues to the pathogenic potential of
      bovine viral diarrhea virus in the bovine fetus.

PMID- 9553719
TI  - Transcriptional modulation of foreign gene expression in engineered somatic
      tissues.
AB  - Many diseases that are candidates for gene therapy require that the therapeutic
      gene expression level be controlled to ensure biological efficacy and to prevent
      toxic effects. Various systems have been described that allow transcriptional
      regulation by artificial chimeric transactivators in mammalian cells. This paper
      describes these various systems and discusses their interests for gene therapy.

PMID- 9553720
TI  - Cationic lipid-mediated gene transfer: analysis of cellular uptake and nuclear
      import of plasmid DNA.
AB  - Cationic lipids are widely used for gene transfer in vitro and show promise as
      vectors for in vivo gene therapy applications. However, there is limited
      understanding of the cellular mechanisms involved in nonviral gene transfer. We
      investigated two major steps that could be limiting barriers to cationic lipid
      mediated gene transfer in vitro. We used a fluorescent plasmid to study the
      cellular uptake and the intracellular fate of lipoplexes during in vitro
      transfection of fibroblast cells and found that 100% of the cells take up
      lipoplexes. The intracellular staining observed with lipoplexes was clearly
      different from that obtained with endocytosed fluorescent dextran. This suggests
      that cells readily take up lipoplexes by a mechanism that could be different from
      endocytosis in our conditions. However, the escape of DNA from intracellular
      vesicles could be a major limiting barrier to gene transfer. Direct injection of
      plasmid DNA into the nucleus and cytoplasm of cells indicated that DNA traffic
      from the cytoplasm to the nucleus might be also an important limiting step.

PMID- 9553721
TI  - Retrovirus-mediated DNA repair gene transfer into xeroderma pigmentosum cells:
      perspectives for a gene therapy.
AB  - The rare hereditary disease xeroderma pigmentosum (XP) is clinically
      characterized by extreme sun sensitivity and an increased predisposition for
      developing skin cancer. Cultured cells from XP patients exhibit hypersensitivity
      to ultraviolet (UV) radiation due to the defect in nucleotide excision repair
      (NER), and other cellular abnormalities. Seven genes identified in the classical
      XP forms, XPA to XPG, are involved in the NER pathway. In view of developing a
      strategy of gene therapy for XP, we devised recombinant retrovirus-carrying DNA
      repair genes for transfer and stable expression of these genes in cells from XP
      patients. Results showed that these retroviruses are efficient tools for
      transducing XP fibroblasts and correcting repair-defective cellular phenotypes by
      recovering normal UV survival, unscheduled DNA synthesis, and RNA synthesis after
      UV irradiation, and also other cellular abnormalities resulting from NER defects.
      These results imply that the first step of cellular gene therapy might be
      accomplished successfully.

PMID- 9553722
TI  - Apoptosis: identification of dying cells.
AB  - Cell death is usually classified into two broad categories: apoptosis and
      necrosis. Necrosis is a passive, catabolic process, always pathological, that
      represents a cell's response to extreme accidental or toxic insults. Apoptosis,
      in contrast, occurs under normal physiological conditions and is an active
      process requiring energy. However, apoptosis can also be elicited in a
      pathological way by toxic injury or during disease processes. In these
      nonphysiological conditions, both types of cell death can be encountered
      following the same initial insult and the balance between death by apoptosis and
      by necrosis appears to depend upon the intensity of the injury and the level of
      available intracellular ATP. It is important, however, to discriminate between
      apoptosis and necrosis in pathological conditions, as therapeutic intervention
      could be considered in apoptotic cell death with putative new pharmacological
      agents aimed at interfering with the key molecular events involved. In most
      cases, none of the current laboratory techniques used alone allows for
      unambiguous identification of apoptotic cells. Some of the most common methods
      based on morphology, biochemistry, and plasma membrane changes are discussed in
      terms of specificity and possible sources of error in data interpretation. As a
      rule, classification of cell death in a given model should always include
      morphological examination coupled with at least one of the other assays.

PMID- 9553723
TI  - Proteases, proteolysis, and apoptosis.
AB  - Proteolytic cleavage of a limited number of cellular proteins is a central
      biochemical feature of apoptosis. Aspartate-specific cysteine proteases, the so
      called 'caspases', are the main enzymes involved in this process. At least ten
      homologues of interleukin-1 beta converting enzyme (ICE), the first described
      human caspase, have been identified so far. The purified active proteins are
      heterodimers with a long and a short subunit derived from a common inactive
      precursor. Crystallized ICE has an original tetrameric structure. The various
      caspases tend to show high degrees of homology around the active site Cys.
      Proteolysis by caspases minimally requires a tetrapeptide substrate in which Asp
      is an absolute requirement in P1 position, the P4 substrate residue is unique to
      each homologue, and much more widespread amino acid substitution is observed in
      P2 and P3. Caspase activation might involve a proteolytic cascade similar to that
      of the coagulation cascade but the molecular ordering of these proteases in vivo
      remains to be established clearly. Calpains, serine proteases, granzymes and the
      proteasome-ubiquitin pathway of protein degradation are other proteolytic
      pathways that have been suggested to play a role in apoptosis. Substrate proteins
      can be either activated or degraded during cell death and the consequences of
      their cleavage remains mostly ill-understood. Nevertheless, the recent
      demonstration that protease inhibitors can rescue mice undergoing acute liver
      destruction indicates the accuracy of therapeutic strategies aiming to inhibit
      cell death-associated proteolysis.

PMID- 9553725
TI  - Mitochondrial permeability transition in apoptosis and necrosis.
AB  - Apoptosis has classically been viewed as a process not involving mitochondria,
      whereas the implication of mitochondrial dysfunction in necrosis has been
      recognized for several decades. Recently, it has become clear that apoptosis
      implies a disruption of mitochondrial membrane intregrity that is decisive for
      the cell death process. Cytofluorometric methods assessing the mitochondrial
      membrane function and structure can be employed to demonstrate that, at least in
      most models of apoptosis, mitochondrial changes precede caspase and nuclease
      activation. Moreover, pharmacological and genetic experiments suggest that the
      loss of mitochondrial membrane integrity is a critical event of the apoptotic
      process, beyond or at the point of no return of programmed cell death. Inhibitors
      of the mitochondrial megachannel (= permeability transition pore) can prevent
      both the mitochondrial and the post-mitochondrial manifestations of apoptosis.

PMID- 9553724
TI  - Proteolytic cleavage of retinoblastoma protein upon DNA damage and Fas-mediated
      apoptosis.
AB  - Proteolytic cleavage of key cellular proteins by caspases (ICE, CPP32, and Ich
      1/Nedd2) may be crucial to the apoptotic process. The retinoblastoma tumor
      suppressor gene is a negative regulator of cell growth and the retinoblastoma
      protein (pRb) exhibits anti-apoptotic function. We show that pRb is cleaved
      during apoptosis induced by either UV irradiation or anti-Fas antibody. Our
      studies implicate CPP32-like activity in the proteolytic cleavage of pRb. The
      kinetics of proteolytic cleavage of pRb during apoptosis differ from that
      observed for other cellular proteins, suggesting that the specific cleavage of
      pRb during apoptosis may be an important event.

PMID- 9553726
TI  - Out of otherness: characters and narrators in the Dutch venereal diseases debates
      1850-1990.

PMID- 9553728
TI  - Intrauterine position, parenting, and nest-site attachment in male Mongolian
      gerbils.
AB  - We housed male Mongolian gerbils, their mates, and foster litters of standardized
      size and sex ratio in enclosures that provided cover in two locations. Males had
      been gestated in known intrauterine positions: either between two females (2F
      males) or between two males (2M males). From Days 1 to 20 postpartum, we examined
      the frequency with which both males and females were in contact with the pups
      they were rearing. We found that 2F males spent more time with pups than did 2M
      males both during entire observation periods and when females were away from the
      nest. Further, when pups were moved from the nest site. 2M males spent more time
      than did 2F males in the vacated nest site. We concluded that 2F male gerbils
      spent more time with pups than 2M males not because of a greater attachment of 2F
      than 2M males to places of concealment, their male, or their nest site. Rather,
      2F males were more attracted to pups than were 2M males.

PMID- 9553727
TI  - Maintenance of arterial pressure in infant rats during moderate and extreme
      thermal challenge.
AB  - It has recently been demonstrated in week-old rats that extreme cold challenges
      that lead to significant bodily cooling result in decreased cardiac rate. To
      determine whether pups are able to maintain arterial pressure in the face of
      decreasing cardiac rate in extreme cold, we measured blood pressure in
      unanesthetized week-old rats. Instrumented pups were thermally challenged and
      thermoregulatory and cardiovascular responses were monitored. Despite pronounced
      decreases in cardiac rate in the cold, pups were able to maintain mean arterial
      pressure (MAP), presumably by increasing peripheral resistance. At the lowest air
      temperature (17 degrees C) pups emitted ultrasonic vocalizations, and these
      emissions were accompanied by pulsatile increases in intraabdominal pressure
      (IAP) and MAP. We hypothesize that these pulsatile increases in IAP during
      extreme cooling reflect the use of the abdominal compression reaction to increase
      venous return during periods of diminished cardiac output.

PMID- 9553729
TI  - The timing of food availability affects growth in chicks.
AB  - Three experiments challenged the ability of domestic chicks to grow normally by
      differentially restricting when and for how long food was available. In
      Experiments 1 and 2, food was available for six 1-hr, three 2-hr, two 3-hr, or
      one 6-hr (a.m., p.m.) periods/day over the first 3 posthatch weeks. Control
      groups received continuous access to food. In Experiment 3, different amounts of
      light surrounded the 6-hr feeding period. In Experiments 2 and 3, chicks composed
      their own diets from separate sources high in protein or carbohydrate. Except for
      the single 6-hr meal preceding dark, large meals at other times of day impaired
      growth--primarily because chicks consumed insufficient dietary protein and ate
      less earlier in the light phase. We conclude that both the amount eaten and the
      proportion of the diet consumed as protein at given times of the day are
      phylogenetically acquired strategies that fit the omnivorous, diurnal chicken to
      its niche, independent of its momentary requirements, and appear early in
      development.

PMID- 9553730
TI  - Stimulus intensity modulates associative and nonassociative responding in
      preweanling rats.
AB  - The purpose of the present study was to determine whether preweanling rats
      respond differentially to the intensity and energy source of a stimulus. Previous
      studies have suggested that infants process compound stimuli based on net
      stimulus intensity regardless of the energy source of the compound's elements,
      but more direct tests have been needed of the infant's response to the stimulus
      attributes of intensity and energy source. This response was tested for auditory
      and visual stimuli that had been equated (Experiment 1) in terms of perceived
      intensity (low and high). Intensity level and energy source of the stimuli were
      varied independently within nonassociative (Experiment 2) and associative
      (Experiment 3) procedures. The overall results indicate that stimuli of a low
      perceived intensity were processed in terms of their intensity, whereas high
      intensity stimuli were processed on the basis of energy source. These results are
      relevant to contemporary issues of cognitive development in humans and animals.

PMID- 9553731
TI  - Primacy and recency effects in rhesus monkeys (Macaca mulatta) using a serial
      probe recognition task. III. A developmental analysis.
AB  - In children, the recency effect emerges prior to the primacy effect. To determine
      whether this dissociation is also seen in nonhuman primates, we evaluated the
      development of the primacy and recency effect in 3 young adult (35 months) and 4
      adolescent (21 months) male rhesus monkeys (Macaca mulatta) using a six-item
      serial probe recognition (SPR) task. As predicted, the young adult monkeys
      displayed both effects, while the adolescent monkeys only displayed the recency
      effect. Not until after 26 months of training on the SPR task did the adolescent
      monkeys exhibit both the primacy and recency effect. Interference and strategy
      differences are discussed in terms of the results along with an interpretation of
      Rudy's (1992) configural association theory of cognitive development. Additional
      possible explanations for this developmental dissociation include the delayed
      maturation of the neocortical, hippocampal, and/or cholinergic systems, the
      latter two having been shown to be important in the expression of the primacy but
      not the recency effect.

PMID- 9553732
TI  - Long-term effects of postnatal manipulation on emotionality are prevented by
      maternal anxiolytic treatment in mice.
AB  - This study investigated the role of maternal behavior on the long-term effects of
      postnatal manipulation (15 min of daily separation from the dam and exposure to
      clean bedding from Day 1 to Day 14 of postnatal life) on emotionality in the
      mouse. Mothers were treated with an antianxiety agent (Chlordiazepoxide: 5
      mg/kg), daily upon removal of the litter from the nest. Emotionality in adult
      offspring was tested in the elevated plus maze. Mice manipulated during postnatal
      development were more explorative and less anxious than unhandled mice, but this
      effect was not observable in the offspring of Chlordiazepoxide-treated dams. No
      effect of maternal Chlordiazepoxide was observed in unhandled offspring. The
      pharmacological treatment of the mother did not affect either pups' ultrasonic
      calling during separation, or maternal behavior far apart from the daily
      manipulation sessions. By contrast, Chlordiazepoxide-treated dams were less
      responsive toward pups upon reunion following daily separation. This alteration
      of dams' behavior was not related to alterations in the amount of ultrasonic
      calls emitted by pups during reunion. Finally, when dams were daily injected with
      Chlordiazepoxide far apart from pups' removal, the pharmacological treatment was
      devoid of effects. These results support the view that the mother-infant
      interaction which follows separation plays a major role in determining the
      effects of postnatal manipulations on adult emotionality.

PMID- 9553733
TI  - Evidence for a phase transition in the early development of prehension.
AB  - A longitudinal study was conducted to examine the hypothesis that the development
      of prehension during the first 5 months of life is characterized by the presence
      of a discontinuous phase transition. Ten infants were observed weekly from 8 to
      24 weeks of age. Video recordings were made of movements toward an attractive
      object which were classified according to two behavioral categories: reaching
      without grasping and reaching with grasping. The time evolution of the relative
      incidence of these behavioral categories was analyzed statistically. Evidence was
      found for a sudden jump from a (developmental) state in which reaching without
      grasping is predominant to a state in which reaching with grasping is
      predominant. Evidence was also found for bimodality, inaccessibility, and
      anomalous variance. In combination, these findings support the hypothesis that
      the investigated behavioral change constitutes a discontinuous phase transition.
      The behavioral change in question occurred at the moment in developmental time at
      which the attractor strength of reaching for objects as such relative to that of
      other behavioral activities appeared to be increased.

PMID- 9553734
TI  - Psychotropic drugs in breast milk: no evidence for adverse effects on prepulse
      modulation of startle reflex or on cognitive level in infants.
AB  - Reversals in modulation of the startle reflex probably reflect maturational
      processes in the central nervous system. This study has investigated the
      longitudinal changes in prepulse modulation of the blink reflex in three groups
      of individual infants: (a) breast-fed infants of mentally ill mothers who were
      prescribed selected psychotropic drugs, (b) bottle-fed infants of similarly ill
      and medicated mothers, and (c) breast-fed infants of healthy control mothers. The
      acoustic stimulation paradigm and neurophysiological methods were similar to
      those used in previous studies and, in addition, the infants' development was
      simultaneously assessed using the Bayley Scales of Infant Development. All the
      infants were found to be developing normally and across all three groups we
      observed a clear transition in prepulse modulation of the eye-blink reflex from
      small inhibition or facilitation in early infancy (1-4 months) to a robust
      facilitation in middle infancy (5-8 months). This reversal probably reflects the
      changing balance of developing neural function in normal infants. There were,
      therefore, no discernible effects in breast-fed infants of exposure to small
      doses of antidepressant or neuroleptic drugs.

PMID- 9553735
TI  - Detection of the low density lipoprotein receptor gene PvuII intron 15
      polymorphism using the polymerase chain reaction: association with plasma lipid
      traits in healthy men and women.
AB  - We have used anchored PCR to amplify and sequence 1400 bp of the 15th intron of
      the Low Density Lipoprotein (LDL) receptor gene, and have determined
      oligonucleotides and conditions for the genotyping of the previously reported
      PvuII polymorphism. The cutting site (CAGCTG) is created by the transition of a
      CpG to a TpG within the sequence CAGCCG at a position roughly 600 bp 5' from the
      splice acceptor site of exon 16. Genotype was determined in three population
      based samples of healthy individuals. In a group of 318 men and women from
      Iceland the frequencies of the Intron-15 T (cutting) allele was 0.23 (95% CI,
      0.19-0.28) and was similar in men and women. In two groups of men from England (n
      = 385) and Scotland (n = 320), the frequency was similar, being 0.23 (0.19-0.27)
      and 0.25 (0.22-0.28) respectively. Individuals who were homozygous for the T
      allele had lower levels of total-cholesterol triglycerides and apolipoprotein B,
      than those with other genotypes, and in the combined group of UK men this effect
      reached statistical significance; compared to the C/C group, the T/T group had 6%
      lower cholesterol (p = 0.02) and 15% lower triglycerides (p = 0.03). The lowering
      effect associated with the T/T genotype was greater in men who were in the lowest
      tertile of body mass index (< 25 kg/m2) and for the trait of apoB levels, this
      genotype x obesity interaction was statistically significant (p = 0.01). We thus
      confirm the association between this allele and lower levels of plasma lipid
      levels previously reported. The availability of a PCR-based method to detect this
      polymorphism will facilitate further investigation of the impact of LDL-receptor
      gene variation in determining lipid levels.

PMID- 9553736
TI  - Fas gene polymorphisms are not associated with systemic lupus erythematosus,
      multiple sclerosis and HIV infection.

PMID- 9553738
TI  - A strategy and demonstration for integrated biotechnology information.
AB  - Bioinformatics has developed as a key discipline to support science. Integrated
      access to the various new and established information resources is a key
      requirement for their future utility. A strategy for this integration has been
      developed and is being demonstrated to a core group of European users.

PMID- 9553737
TI  - Analysis of the association of a heat shock protein70-1 gene promoter
      polymorphism with myocardial infarction and coronary risk traits.
AB  - Heat shock proteins (HSP) are induced during coronary ischaemia, and abnormal
      expression of one HSP gene may cause hypertension in rats. We examined
      association of a promoter polymorphism in the major stress-inducible hsp70 gene
      (hsp70-1 or HSP70A1) on chromosome 6 (p21.3) with coronary disease traits. This C
      ->A base substitution (AAACCCC) is at nucleotide position-110 in the heat shock
      transcription factor binding site (heat shock element, HSE). The first study
      sample (ECTIM), recruited from Belfast and three centers in France, consisted of
      578 myocardial infarction cases and 698 age-matched controls. The frequency of
      the A-110 allele was 0.381 (95% CI = 0.35-0.41) and 0.384 (95% CI = 0.36-0.41) in
      cases and controls respectively. Homozygotes for the rarer A-110 allele had a
      higher BMI (27.3 kg/m2 +/- 3.9) compared with homozygotes for the common C-110
      allele (26.3 kg/m2 +/- 3.3). The rarer homozygotes were shorter and heavier than
      the common homozygotes. A follow-up study involved 1431 healthy, middle aged men
      from the UK (NPHS II group). The frequency of the A-110 allele was 0.385 (95% CI
      = 0.37-0.40), and there was no association of genotype with BMI. Thus there
      appears to be no strong association of the Hsp70-1 promoter polymorphism with
      risk of myocardial infarction, BMI or any coronary disease traits analysed here.

PMID- 9553739
TI  - Comparison of commercial ELISA for detection of antibodies to the viral capsid
      antigen (VCA) of Epstein-Barr virus (EBV).

PMID- 9553740
TI  - Haplotypes of the endogenous retrovirus HRES-1 in multiple sclerosis patients and
      healthy control subjects of Shanghai Chinese origin.

PMID- 9553741
TI  - Alpha 1-antichymotrypsin mutations in patients with chronic obstructive pulmonary
      disease.
AB  - Mutations in the alpha 1-antichymotrypsin gene have been described which result
      in reduced levels of alpha 1-antichymotrypsin in the serum. Previous studies have
      suggested that two of these mutations (Pro227-->Ala and Leu55-->Pro) predispose
      to chronic obstructive pulmonary disease (COPD). We have investigated the
      prevalence of these mutations in 168 COPD patients and 61 controls without
      airflow obstruction. The prevalence of the Pro227-->Ala mutation was 0.9% and it
      was not associated with impaired lung function. None of the subjects had the
      Leu55-->Pro mutation.

PMID- 9553742
TI  - BRCA1: a review of structure and putative functions.
AB  - BRCA1 is a complex gene implicated in familial breast and ovarian cancer.
      Although it is almost certainly a tumour suppressor, it is also essential for the
      normal growth and development of embryonic cells. BRCA1 is probably involved in
      DNA damage and repair, in cell cycle regulation, and in differentiation of cells.
      It remains to be established whether all these functions are subserved by single
      mechanism or pathway. Since the cloning of BRCA1 in 1994, much has been learned
      about the function of the gene. However, a great deal more still has to be
      uncovered. The size of the protein coded by the BRCA1 gene and the variety of
      transcripts argues for a complexity of function and regulation that will provide
      intellectual and technical challenges for years to come.

PMID- 9553743
TI  - Effects of muscle fatigue and temperature on electromechanical delay.
AB  - The effect of repeated maximal isometric knee extensions on electromechanical
      delay (EMD) and associated muscle temperature changes were investigated on seven
      college aged subjects. The exercise produced a significant reduction in muscle
      contraction force, rate of force development and muscle conduction velocity,
      whilst the muscle temperature increased by 2.1 degrees C. The EMD increased from
      a pre-exercise value of 38.4 (SEM 3.4) ms to 55.7 (SEM 3.4) ms post-exercise. In
      an attempt to evaluate the effect of muscle temperature on EMD, hot and ice-water
      bags were placed on the quadriceps muscle to alter muscle temperature. The EMD in
      isometric maximal knee extension was measured at 38, 36, 34, 32 and 30 degrees C.
      The results showed that the EMD elongated at muscle temperatures either lower or
      higher than 36 degrees C. It was speculated that the increased muscle temperature
      might contribute to 20-25% of the EMD elongation found during the fatiguing
      intermittent exercise. The information of the effects of muscle temperature on
      EMD could be useful when evaluating the effects of strenuous exercise, in which a
      substantial muscle temperature change might occur, on the time delay between
      myoelectrical activity and force generation.

PMID- 9553744
TI  - Quantitative electromyographical changes in cervical dystonia after treatment
      with botulinum toxin.
AB  - Injection of botulinum toxin (BT) into affected neck muscles gives symptomatic
      relief to patients with cervical dystonia by causing a presynaptic block of
      acetylcholine release. In a retrospective study of 19 patients, we used the turns
      amplitude analysis of the EMG interference pattern for the evaluation of
      electrophysiological changes as a function of time after BT treatment. EMG was
      performed immediately before and during injection, and muscles showing abnormally
      increased activity (> 100 turns/s at rest) were given botulinum toxin A (Oculinum
      (= Botox)) 40-120 units. A second EMG was done 6-30 weeks later. At attempted
      rest, the sternocleidomastoid muscle contralateral to the involuntary head
      rotation showed the most pronounced changes, possibly due to relatively large
      doses of BT, and the EMG changes were related to the time after BT treatment. Six
      weeks after treatment the muscle showed decreased turns/s, mean amplitude and
      ratio (turns/amplitude) at rest. At 30 weeks, turns and mean amplitude reached
      values as before treatment, while ratio was increased to 175% of the pre
      treatment value. This pattern may reflect a reversible and random loss of muscles
      fibres, due to presynaptic denervation. At maximal voluntary contractions, no
      correlation was seen between time after BT treatment and quantitative EMG.

PMID- 9553745
TI  - Cortical representation of proximal and distal arm muscles as assessed by focal
      transcranial magnetic stimulation.
AB  - In 21 healthy volunteers, a mapping of cortical areas from which motor evoked
      potentials in deltoid muscle and first dorsal interosseal muscle (FDI) could be
      elicited by focal transcranial magnetic stimulation was performed. For this
      purpose, magnetic stimuli were applied using a figure-of-eight shaped magnetic
      coil and a Magstim 200 stimulator at an intensity of 15% above motor threshold
      for the deltoid muscle. There was a considerable overlap between the cortical
      areas from which motor responses of the two muscles could be evoked with the FDI
      represented more laterally than the deltoid muscle. The cortical location from
      which maximal amplitudes of motor evoked potentials were elicited was 4-8 cm
      lateral of Cz with the FDI and 2-6 cm lateral of Cz with the deltoid muscle.
      Calculated centres of cortical points with maximal muscle responses were
      significantly separated with the FDI represented 5.7 cm lateral of Cz and deltoid
      muscle 4.3 cm lateral of Cz. The anterior-posterior extension of the cortical
      maps did not show significant differences between the proximal and distal arm
      muscle. In no subject an ipsilateral representation of either muscle could be
      found even when stimulating at maximal intensity.

PMID- 9553746
TI  - Inhibitory influence of soleus massage onto the medial gastrocnemius H-reflex.
AB  - It has previously been reported that the soleus Hoffmann (H-)reflex is diminished
      in amplitude during a massage of the ipsilateral triceps surae. A question arises
      as to the origin of this decrease. The purpose of this study was to determine
      whether massage does indeed diminish motoneuronal excitability or whether the
      decrease is an artefact associated with the experimental procedures, i.e.
      saturation of the transmission capacity of the afferent pathway. H-reflexes and
      the corresponding muscle (m-)responses were recorded from the medial
      gastrocnemius (MG) muscle during a 3-minute massage of the ipsilateral soleus
      muscle in 12 neurologically healthy adults during 4 control conditions (C1, C2,
      C4, C5) and 1 experimental (C3-massage) condition. Peak-to-peak mean amplitudes
      of the MG H-reflex obtained during massage were significantly reduced in
      comparison to all control values recorded while the subjects were at rest. These
      results suggest that massage does indeed diminish motoneuronal excitability,
      since these effects were not restricted to the homonymous motoneurone pool, but
      could also be demonstrated for a close synergistic muscle, uninvolved in the
      massage.

PMID- 9553747
TI  - Electrophysiological findings in hereditary motor and sensory neuropathy type I
      and II--a conduction velocity study.
AB  - We performed clinical and electrophysiological studies in 42 children with
      hereditary motor and sensory neuropathy type I and II (HMSN I and HMSN II) and in
      103 members of their families. In 24 families with HMSN I the conduction velocity
      and the latency were markedly changed in the nerves innervating the distal
      muscles (median, peroneal nerves), as well as proximal muscles (facial, axillary,
      and musculocutaneous nerves). The changes were uniform in all motor and sensory
      nerves studied in the particular patient. No nerve conduction worsening with age
      has been found in cross-sectional analysis. In patients with HMSN I the
      conduction velocity was impaired even when the clinical abnormalities were
      minimal. The degree of the conduction velocity slowing was uniform within
      majority of the families. Homogeneity of conduction velocity slowing in
      individuals with HMSN I regardless of clinical expression suggests a primary
      myelin defect as an underlying cause. In patients from 18 families with HMSN II
      slight changes in conduction velocity were found only in the nerves innervating
      the distal muscles, the latency of axillary and facial nerves was within normal
      range. We recommend examining conduction time in facial and axillary nerves as a
      useful procedure for differentiation between HMSN I and II, especially in
      families with borderline conduction values in the long nerves.

PMID- 9553748
TI  - Analysis of interaction of spinal and supraspinal reflex pathways involved in
      physiological tremor.
AB  - A model of feedback type in which physiological tremor are produced by both
      muscular skeletal system and reflex action is described. Analysis of this model
      shows that the interaction between the spinal and the supraspinal reflex pathways
      is important in responsible for low and high frequency oscillations of
      physiological tremor. Particularly the effect of gain ratio of the two pathways
      is studied in order to examine the role for the two reflex pathways in
      controlling neuromuscular oscillations. The existence of a critical point of the
      gain ratio at which one oscillating frequency transitions to two ones is
      predicted theoretically. A shift of the critical point with variations of weight
      load is found and suggests a changeable correlation relation between the spinal
      and the supraspinal pathways due to loading conditions. Our computations for
      physiological tremor demonstrate the results that the high frequency component of
      about 25 Hz is produced by the muscle-spinal reflex loop, and the low frequency
      component of about 10 Hz originates from the central nervous system or from
      supraspinal reflex loop. Several relations derived in this study are described,
      and they can be compared with experimental observations. Our model sheds
      considerable light on the details of the possible mechanism for physiological
      tremor. In addition, a possibility arising from our study is that the tremulous
      oscillation associated with some pathological states, say Parkinson's disease,
      may arise from modified gains in one or more of the reflex pathways.

PMID- 9553749
TI  - Double crush syndrome in lower extremities.
AB  - Retrospective analysis of results of electromyography and nerve conduction
      velocity was performed in 169 patients with lower back pain, mostly caused by
      trauma. A total 289 peroneal, 280 posterior tibial and 301 sural nerves were
      included in statistical analysis. Peripheral entrapment of nerves (tarsal tunnel
      syndrome and anterior tarsal tunnel syndrome) were found in 5.3% of patients,
      signs of acute or chronic partial muscle denervation of corresponding muscles of
      lower extremities in 21.8% of patients, and abnormally prolonged F-wave latency
      in 12.5% of patients. Combined partial denervation and abnormally prolonged F
      wave latency were found in 6.2% of patients, combined partial denervation and
      peripheral entrapment of nerves in 4.4% of patients, combined abnormally
      prolonged F-wave latency and peripheral entrapment of nerves in 2.4% of patients
      and combined partial denervation, abnormally prolonged F-wave latency and
      peripheral entrapment of nerves in 3.5% of patients. Statistical analysis of
      these data showed significantly higher than random overlap of peripheral
      entrapment syndromes and signs of proximal nerve damage of the corresponding
      nerves (partial muscle denervation or abnormalities of F-wave). This higher than
      random coincidence of the two conditions strongly suggests cause-and-effect
      relationship of damage of the proximal stretch of motor nerve fibers and
      development of peripheral entrapment syndromes in the same nerves rather than a
      random coincidence of two independent pathologies. Appreciation of this causal
      relationship is important in the development of comprehensive approach to
      treatment of peripheral entrapment syndromes. In appropriate cases, simultaneous
      treatment of the lower back problem should be considered as well.

PMID- 9553750
TI  - Continuous muscle fibre activity: description of neuroelectromyographic findings
      including single fibre EMG.
AB  - Four patients with continuous muscle fibre activity (Isaacs-Mertens syndrome) are
      reported in this communication. Electrophysiological evidence of peripheral
      neuropathy was present in two patients. Impulse induced repetitive CMAPs were
      noted in two patients. In one case the repetitive activity increased upon
      proximal stimulation. Single fibre EMG recordings of the spontaneous activity
      revealed pathological discharges with variable frequencies. Each pathological
      discharge comprised of a primary discharge and 1-4 extradischarges. There was
      marked variability of the interval between the primary discharge and subsequent
      extradischarges.

PMID- 9553751
TI  - Distribution and functional significance of angiotensin-II AT1- and AT2-receptor
      subtypes in the rat adrenal gland.
AB  - The distribution and the functional significance of angiotensin-II (ANG-II)
      receptor subtypes, AT1 and AT2, in the rat adrenal gland has been investigated in
      vitro. Autoradiographic assessment of the selective displacement of [125I]ANG-II
      binding by selective ligands of the two receptor subtypes indicated that zona
      glomerulosa (ZG) was provided with both AT1 and AT2, and adrenal medulla (AM)
      almost exclusively with AT2 receptors. ANG-II (10(-9) M) evoked a marked rise in
      the secretion of aldosterone by dispersed ZG cells and catecholamines by AM
      fragments. The selective AT1-receptor antagonist DuP753 blocked aldosterone
      response to ANG-II, while the selective AT2-receptor antagonist PD123319 was
      ineffective. Catecholamine response to ANG-II was inhibited by PD123319 and only
      moderately affected by high concentrations of DuP753. The selective AT2-receptor
      agonist CGP42112 did not change basal aldosterone release of ZG cells, but
      concentration-dependently enhanced basal catecholamine release by AM fragments.
      In light of these findings the conclusion is drawn that in the rat the
      aldosterone secretagogue effect of ANG-II is exclusively mediated by the AT1
      receptors present in the ZG, while the catecholamine secretagogue action
      preminently involves the activation of AT2 receptor located on medullary
      chromaffin cells.

PMID- 9553753
TI  - Castration differentially regulates nitric oxide synthase in the hypothalamus and
      pituitary.
AB  - Mammalian reproductive function is under control of the integrated hypothalamic
      pituitary-gonadal (HPG) axis. Castration in male rats has been utilized as an
      effective tool to investigate hormonal interactions in the mammalian HPG axis.
      Recently, nitric oxide (NO) has been suggested to play a role in HPG hormonal
      regulation. In order to gain further insight into the function of the NO-NOS
      system in reproductive neuroendocrine control, particularly in the gonadal
      feedback regulation of the hypothalamic-pituitary unit, we examined steady state
      levels of nNOS mRNA, nNOS protein, and the important physiological index, NOS
      enzyme activity, of the intrinsic NOergic system in both hypothalamus and
      pituitary in castrated male rats and their sham-operated counterparts one week
      after surgery. In the pituitary, we found a significant four-fold increase in
      nNOS mRNA, p < 0.0003 compared to sham. Castration also resulted in a four-fold
      rise in pituitary nNOS protein, p < 0.02 compared to sham. Pituitary NOS enzyme
      activity was stimulated 2 fold, p < 0.003 after castration. In the hypothalamus,
      conversely, we observed no significant castration-modulated difference in either
      nNOS mRNA, nNOS protein or NOS enzyme activity. Thus, it appears that the
      hypothalamic NO-NOS system is either not required for hypothalamic adaptations to
      castration, although important in the release of LHRH under normal physiological
      conditions, or alternatively, the hypothalamus may become more sensitive to the
      effects of NO in the castrated state. In the pituitary, NO may attenuate the
      gonadotropin response to castration as a local balancing mediator.

PMID- 9553752
TI  - The AT2 receptor-mediated stimulation of adrenal catecholamine release may
      potentiate the AT1 receptor-mediated aldosterone secretagogue action of
      angiotensin-II in rats.
AB  - The role played by AT1 and AT2 receptors in the mediation of angiotensin-II (ANG
      II) aldosterone secretagogue action has been investigated in vitro using
      different types of rat adrenal preparations. ANG-II enhanced aldosterone
      secretion of dispersed zona glomerulosa (ZG) cells in a concentration-dependent
      manner (EC50, 3 x 10(-10) M), and its effect was annulled by the AT1-receptor
      antagonist DuP753 and unaffected by the AT2-receptor antagonist PD123319. ANG-II
      was significantly more effective in stimulating aldosterone secretion when
      capsule-ZG and adrenal slices containing medullary chromaffin cells were used
      (EC50, 1 x 10(-11) M and 7 x 10(-12) M, respectively); moreover, both DuP753 and
      PD123319 caused partial reversals (intense and moderate, respectively) of the
      responses to ANG-II, and when added together annulled them. The beta-adrenoceptor
      antagonist l-alprenolol did not affect aldosterone response to ANG-II of
      dispersed ZG cells, but exerted a PD123319-like effect on the responses of
      capsule-ZG and adrenal slices. In light of these findings we conclude that, when
      the integrity of adrenal tissue is preserved, ANG-II stimulates aldosterone
      secretion by activating both AT1 and AT2 receptors, the major role being played
      by AT1 receptors located on ZG cells. The activation of AT2 receptors probably
      elicits the local release of catecholamines, which in turn enhance aldosterone
      secretion in a paracrine manner acting through the beta-adrenoceptors with which
      ZG cells are provided.

PMID- 9553754
TI  - Characteristics of biochemical markers in patients with metabolic bone disorders.
AB  - Biochemical markers of bone turnover are expected to have some different
      characteristics among bone metabolic disorders. We compared bone formation
      markers: serum total alkaline phosphatase (s-Alp), serum osteocalcin (s-OC) and
      serum carboxy-terminal propeptide of type I collagen (s-PICP); and bone
      resorption markers: serum carboxy-terminal telopeptide of type I collagen (s
      ICTP), urinary pyridinoline (u-Pyr) and urinary deoxypyridinoline (u-Dpyr) to
      examine which marker is the most suitable and reliable to evaluate bone turnover
      in patients with osteoporosis (n = 29), osteomalacia (n = 10), primary
      hyperparathyroidism (n = 6) and renal osteodystrophy (n = 21). The value of s-Alp
      in the osteomalacia group was significantly higher than those in the normal
      control group and the osteoporosis group (p < 0.001), and T-score of s-Alp was
      significantly higher than those of s-OC and s-PICP in the osteomalacia group. The
      values of u-Pyr and u-Dpyr in the primary hyperparathyroidism group were
      significantly higher than those in the other groups (p < 0.001). S-PICP, which
      are not dependent upon renal function, was much higher in the renal
      osteodystrophy group than in all other groups. In the osteoporosis group, T-score
      of s-ICTP was significantly higher than those of s-OC. Thus, s-Alp was a good
      marker in osteomalacia, u-Pyr and u-Dpyr in primary hyperparathyroidism, s-PICP
      in renal osteodystrophy, and s-ICTP in osteoporosis.

PMID- 9553755
TI  - Pretreatment with glucocorticoid is essential for lactogenic induction of the
      bovine beta-casein/CAT expression in HC11 cells.
AB  - Hormonal regulation of the bovine beta-casein gene expression was studied in a
      murine mammary epithelial HC11 cells and compared with that of the rat beta
      casein gene expression. CAT expression vectors driven by their promoter sequences
      were transfected into HC11 cells. Stable transfectents were treated with
      lactogenic hormones, dexamethasone and prolactin for 2 days in confluent
      cultures. While the lactogenic hormones synergistically induced a strong
      activation of the rat beta-casein/CAT expression, neither a single or combined
      treatment of dexamethasone and prolactin induced the bovine beta-casein/CAT
      expression. To test a sequential treatment effect of lactogenic hormones on the
      bovine beta-casein/CAT expression, cells were first treated with either
      dexamethasone or prolactin for various days and then subjected to the second
      treatment with both hormones for 2 days. Only dexamethasone-, but not prolactin
      pretreated cells showed a strong lactogenic induction. Moreover, the fold
      induction of dexamethasone-pretreated cells increased gradually as a function of
      duration of dexamethasone pretreatment. A series of the bovine beta-casein/CAT
      constructs with different length of the bovine beta-casein 5' flanking region
      ranged from 0.3 kb to about 15 kb was analyzed in 12-days dexamethasone
      pretreated cultures. CAT expression was increased even in 0.3 kb-containing
      construct, but prominent induction was seen in more than 1.8 kb-containing
      constructs. Therefore, it could be concluded that a long-term dexamethasone
      pretreatment is essential for lactogenic induction of the bovine beta-casein
      expression and the 0.3 kb proximal promoter region is important, but more distal
      promoter element(s) is necessary for mediating the coordinated action of
      lactogenic hormones to the bovine beta-casein expression.

PMID- 9553756
TI  - Catalase transfection decreases hydrogen peroxide toxicity in a pancreatic beta
      cell line.
AB  - BetaTC6-F7 cells like normal Beta cells were found to be highly sensitive to
      hydrogen peroxide and to possess very low levels of catalase. Therefore we tested
      whether overexpression of catalase could enhance resistance to hydrogen peroxide.
      Enzyme activity was increased forty fold by transient transfection of a catalase
      transgene. To assess protection from hydrogen peroxide a cotransfection method
      using a human growth hormone reporter gene was developed. Human growth hormone
      secretion was shown to be a suitable marker for insulin secretion since both
      hormones demonstrated virtually identical glucose dose response curves. Catalase
      transfection was found to provide significant protection against hydrogen
      peroxide indicating that low catalase may contribute to the sensitivity of cells
      to hydrogen peroxide.

PMID- 9553757
TI  - Interaction of estradiol, progesterone and corticosterone on uterine connective
      tissue degrading enzymes.
AB  - The impact of ovarian hormones and corticosterone acetate on uterine connective
      tissue degrading enzymes were studied in mature albino rats. Ovariectomy resulted
      in a significant increase in the activities of alpha- and beta-galactosidases and
      glucosidases in the uterus. Administration of estradiol to ovariectomized rats
      brought back the activities of alpha-galactosidase and alpha-glucosidase to
      normalcy. While beta-galactosidase and beta-glucosidase were significantly
      decreased. Administration of progesterone to ovariectomized rats resulted in the
      increase of alpha- and beta-galactosidases and glucosidases. Administration of
      corticosterone to ovariectomized rats produced a further increase in alpha- and
      beta-galactosidases and glucosidases in the uterus. Adrenalectomy in ovary intact
      rats produced a decrease in alpha-galactosidase however, beta-glucosidase was
      significantly increased. Administration of corticosterone to ovary intact rats
      significantly increased the activities of alpha- and beta-galactosidases, while
      alpha- and beta-glucosidases were found to be decreased. Ovariectomy resulted in
      a significant increase in the activities of cathepsin-D and cathepsin-E.
      Administration of estradiol to ovariectomized rats brought back the activity of
      cathepsin-D to normalcy, whereas cathepsin-E was significantly increased.
      Administration of progesterone as well as estradiol to ovariectomized rats
      significantly increased the levels of cathepsin-E, however, cathepsin-D was
      brought back to normalcy. Administration of corticosterone to ovariectomized rats
      as well as ovariectomy + adrenalectomy significantly increased the activity of
      cathepsin-D and cathepsin-E. Adrenalectomy significantly decreased the activity
      of cathepsin-D, while administration of corticosterone increased the cathepsin-D
      and cathepsin-E in the uterus. Therefore, these results suggest that estradiol is
      a potent ovarian steroid protecting the extra cellular matrix components. The
      effect of progesterone appears to modulate and act hand in hand with estradiol.
      Corticosterone appears to have an opposite effect to that of estradiol.

PMID- 9553759
TI  - [Schizophrenia and quality of life--therapeutic aims to be re-interpreted].

PMID- 9553760
TI  - Ecto-enzymes of lymphoid cells.

PMID- 9553758
TI  - Plasma atrial natriuretic hormone in hyperthyroidism.
AB  - In 22 hyperthyroid patients, atrial natriuretic hormone (ANH) levels (71.91 +/-
      21.03 pg/ml), measured during a 3-h-Holter, were found to be significantly higher
      (p < 0.001) than those in 20 age-matched normal subjects (37.22 +/- 8.73 pg/ml).
      We have demonstrated that the presence of tachiarrhythmias does not influence ANH
      release. The positive and significant correlation of FT3 with both ANH and heart
      rate confirms the hypothesis of a direct action of thyroid hormones on ANH
      release.

PMID- 9553761
TI  - Ecto-phosphodiesterase/pyrophosphatase of lymphocytes and non-lymphoid cells:
      structure and function of the PC-1 family.
AB  - Many developmentally regulated membrane proteins of lymphocytes are ecto-enzymes,
      with their active sites on the external surface of the cell. These enzymes
      commonly have peptidase, phosphodiesterase or nucleotidase activity. Their
      biological roles are just beginning to be discovered. Although their expression
      is usually associated with particular stages of lymphoid differentiation, the
      same gene products are often expressed on the surface of certain non-lymphoid
      cell types outside the immune system, indicating that their functions cannot be
      unique to lymphocytes, nor can they be ubiquitous. The plasma cell membrane
      protein PC-1 (phosphodiesterase I; EC 3.1.4.1/nucleotide pyrophosphatase; EC
      3.6.1.9), which was one of the first serological markers for lymphocyte subsets
      to be discovered, is a typical example. Within the immune system, PC-1 is
      confined to plasma cells, which represent about 0.1% of lymphocytes. However, PC
      1 is also expressed on cells of the distal convoluted tubule of the kidney,
      chondrocytes, osteoblasts, epididymis and hepatocytes. Recent work has shown that
      PC-1 is a member of a multigene family of ecto-phosphodiesterases that currently
      has two other members, PD-1 alpha (autotaxin) and PD-1 beta (B10). Within this
      family, the extracellular domains are highly conserved, especially around the
      active site. In contrast, the transmembrane and cytoplasmic domains are highly
      divergent. Individual members of the eco-phosphodiesterase family have distinct
      patterns of distribution in different cell types, and even within the same cell.
      For example, PC-1 is present only on the basolateral surface of hepatocytes,
      while B10 (PD-1 beta) is confined to the apical surface. Analysis of conservation
      and differences in the sequence of their cytoplasmic tails may illuminate
      intracellular targetting signals. Ecto-phosphodiesterases may play a part in
      diverse activities in different tissues, including recycling of nucleotides. They
      may also regulate the concentration of pharmacologically active extracellular
      compounds such as adenosine or its derivatives and cell motility. Some members
      may modulate local concentrations of pyrophosphate, and hence influence
      calcification in bone and cartilage.

PMID- 9553762
TI  - Enzymatic and extraenzymatic role of ecto-adenosine deaminase in lymphocytes.
AB  - Adenosine deaminase (ADA, EC 3.5.4.4) is an enzyme of the purine metabolism which
      has been the object of considerable interest mainly because the congenital defect
      causes severe combined immunodeficiency (SCID). In the last 10 years, ADA, which
      was considered to be cytosolic, has been found on the cell surface of many cells
      and, therefore, it can be considered an ecto-enzyme. There is recent evidence
      about a specific role of ecto-ADA, which is different from that of intracellular
      ADA. Apart from degrading extracellular adenosine (Ado) or 2'-deoxyadenosine
      (dAdo), which are toxic for lymphocytes, ecto-ADA has an extraenzymatic function
      via its interaction with CD26. ADA/CD26 interaction results in co-stimulatory
      signals in T cells. This co-stimulation is blocked by HIV-1, thus evidencing a
      role for ecto-ADA in the pathophysiology of AIDS. The fact that, besides CD26,
      ADA can interact with different cell-surface proteins opens new perspectives in
      the research for a role of ecto-ADA in the function of the immune system and in
      the interactions that take place between different cells in the development of
      the immune system. The most interesting aspect is the possible participation of
      the ecto-enzyme in cell-to-cell contacts during ontogenesis and maturation of
      immunocompetent cells.

PMID- 9553763
TI  - Dipeptidyl-peptidase IV/CD26 on T cells: analysis of an alternative T-cell
      activation pathway.
AB  - CD26 is a proteolytic enzyme (dipeptidyl-peptidase IV) with a wide tissue
      distribution and a unique specificity that was already described 27 years ago.
      CD26 is expressed on a fraction of resting T cells at low density but is strongly
      upregulated following T-cell activation. Recent results indicate that CD26 is a
      multifunctional molecule that may have important functions on T cells and in the
      immune system. It is associated with molecules of immunological importance such
      as the protein tyrosine phosphatase CD45 and adenosine deaminase (ADA) on the
      cell surface. Synthetic inhibitors of the enzymatic activity of CD26 have been
      shown to suppress certain immune reactions in vitro and in vivo. An interesting
      feature of CD26 is its ability to transmit a transmembrane signal to trigger
      functional programs in T cells. This triggering requires crosslinking of CD26 on
      a cell membrane. The enzymatic activity of CD26 is not obligatory for the
      activation of T cells via CD26. Since CD26 is a type II membrane protein with
      only six intracellular amino acids, it must deliver its signal via a signal
      transducing molecule. Signaling is dependent on the expression of the T-cell
      receptor (TCR) complex with a special need for a functional zeta-chain. In this
      context the zeta-chain of the TCR complex is required for CD26-mediated signaling
      but, in contrast to other co-stimulatory molecules such as the CD2 molecule, is
      not sufficient for triggering the T cell.

PMID- 9553764
TI  - The structure and function of CD26 in the T-cell immune response.
AB  - CD26 is a widely distributed 110 kD cell-surface glycoprotein with known
      dipeptidyl-peptidase IV (DPP-IV) activity in its extracellular domain. This ecto
      enzyme is capable of cleaving amino terminal dipeptides from polypeptides with
      either L-proline or L-alanine in the penultimate position. On human T cells, CD26
      expression appears late in thymic differentiation and is preferentially
      restricted to the CD4+ helper/memory population, and CD26 can deliver a potent co
      stimulatory T-cell activation signal. The cDNA sequence of CD26 predicts a type
      II membrane protein with only 6 amino acids in its cytoplasmic region, suggesting
      that, in addition to DPP-IV enzyme activity, other signal-inducing molecules may
      be associated with CD26. Considerable evidence exists that CD26 interacts,
      presumably in its extracellular domain, with both CD45, a protein tyrosine
      phosphatase, and adenosine deaminase (ADA), each of which is capable of
      functioning in a signal transduction pathway. In addition, CD26 is the receptor
      for ADA, and ADA on the cell surface is involved in an important immunoregulatory
      mechanism by which released ADA binds to the cell-surface ADA. This
      multifunctional molecule may be involved in cell migration and the HIV-1
      associated loss of CD4+ cells through the process of programmed cell death. Thus,
      CD26 appears to play a key role in a number of aspects of lymphocyte function.

PMID- 9553765
TI  - The enigmatic role of glutamyl aminopeptidase (BP-1/6C3 antigen) in immune system
      development.
AB  - The murine B-lymphocyte differentiation antigen BP-1/6C3, a homodimeric integral
      membrane protein composed of M, 140,000 subunits, has been identified as glutamyl
      aminopeptidase (EAP, EC 3.4.11.7). This ecto-enzyme cleaves acidic amino acid
      residues from the amino terminal of polypeptide substrates such as angiotensin II
      and cholecystokinin-8. Although BP-1/6C3/EAP is expressed by cells in many
      tissues, among hematopoietic cell lineages this ecto-enzyme is restricted to
      immature B-lineage cells where its expression is upregulated by interleukin-7 and
      viral transformation. BP-1/6C3/EAP thus serves as a valuable marker of
      progression along the B-cell differentiation pathway, but a corresponding
      biological role has not yet been established.

PMID- 9553766
TI  - CD38: a new paradigm in lymphocyte activation and signal transduction.
AB  - CD38 is a type II transmembrane glycoprotein that is extensively expressed on
      cells of hematopoietic and non-hematopoietic lineage. Although the intracellular
      domain of CD38 is not homologous to any known proteins, the extracellular domain
      of CD38 is structurally related to enzymes in the ADP-ribosyl cyclase family. The
      structural homology between CD38 and the cyclase family members extends to
      functional homology, as the extracellular domain of CD38 can mediate the
      catalysis of beta-NAD+ into nicotinamide, ADP-ribose (ADPR) and, to a lesser
      extent, into cyclic ADPR-ribose (cADPR). Extensive investigation in other systems
      has shown that cADPR is an important regulator of intracellular Ca2+ release.
      Since engagement of CD38 on hematopoietic cells with anti-CD38 Abs has been shown
      to have potent effects on a number of in vitro cellular responses, we have
      speculated that cADPR might control CD38-mediated signal transduction. However,
      it has been difficult to understand how a mediator which is typically an
      intracellular signaling molecule could potentiate its effects from an
      extracellular location, thus posing a dilemma which pertains to all ecto-enzymes
      and the mechanisms by which they regulate signal transduction and cellular
      processes. This review describes the biologic properties of murine CD38, its role
      in humoral immunity, and its signal transduction properties in B lymphocytes. We
      suggest that signaling through CD38 represents a new paradigm in lymphocyte
      signal transduction and is predicated upon extracellular, rather than
      intracellular, crosstalk.

PMID- 9553767
TI  - Ecto-enzyme and signaling functions of lymphocyte CD73.
AB  - CD73 or ecto-5'-nucleotidase (5'-NT) is a widely expressed ecto-enzyme which
      catalyzes the dephosphorylation of AMP and other nucleoside monophosphates. CD73
      participates in purine salvage through this enzymatic activity, supplying cells
      with precursors for energy metabolism and nucleic acid biosynthesis. As an enzyme
      that produces adenosine, CD73 can also regulate adenosine receptor engagement in
      many tissues. However, CD73 also has functions independent of its enzyme
      activity. Like many glycosyl phosphatidylinositol (GPI)-anchored molecules, it
      transmits potent activation signals in T cells when ligated by antibodies. Less
      compelling evidence suggests that CD73 may function as a cell adhesion molecule.
      In the human immune system, CD73 is expressed on subsets of T and B cells, on
      germinal center follicular dendritic cells, and on thymic medullary reticular
      fibroblasts and epithelial cells. Many challenging areas remain to be explored
      before the role of CD73 in the immune system will be fully understood. These
      include an evaluation of the role of adenosine receptors in lymphoid development,
      the identification of physiological CD73 ligands, a functional assessment of the
      GPI anchor, and an analysis of the intricate cell-type-specific and developmental
      regulation of CD73 expression.

PMID- 9553768
TI  - Ecto-ATPase: an activation marker necessary for effector cell function.
AB  - Ecto-ATPase, a transmembrane enzyme that catalyzes the hydrolysis of
      extracellular ATP (ATPe) to ADP and inorganic phosphate, is expressed upon cell
      activation. Ecto-ATPase is inhibited by non-hydrolyzable ATP analogues, which are
      competitive inhibitors of the catalytic reaction, and the ATP analogue affinity
      label. 5'-p-(fluorosulfonyl)benzoyl adenosine (5'-FSBA), which irreversibly
      inhibits the catalytic activity. These nucleotide antagonists do not cross the
      cell membrane and are specific for ecto-ATPase in T cells, B cells and NK cells.
      Inhibition of ecto-ATPase by both reversible and irreversible nucleotide
      antagonists results in the inhibition of antigen-induced cytokine secretion and
      cytolytic activity of T cells. Likewise, granule release and cytolytic activity
      of NK cells as well as antibody secretion and spontaneous proliferation by B-cell
      hybridomas are inhibited. Inhibition of ecto-ATPase does not influence effector
      cell-target cell conjugate formation, but acts, in part, by regulating the influx
      of extracellular calcium that is necessary to maintain cellular activation. Thus,
      further elucidation of ecto-ATPase regulation and expression and its interaction
      with intracellular signal transduction events will provide a basis for
      understanding the role of the hydrolysis of ATPe by ecto-ATPase in lymphocyte
      effector function.

PMID- 9553769
TI  - Carboxypeptidase M as a marker of macrophage maturation.
AB  - During terminal maturation of blood monocytes (MO) into macrophages (MAC), a
      multitude of phenotypic and functional changes occur: cells increase in size and
      enhance their capacity for phagocytosis and tumor cytotoxicity, but decrease
      their ability for T-lymphocyte stimulation. The pattern of secreted cytokines is
      shifted as is the profile of surface antigens. The identity of the MAC maturation
      associated antigen MAX.I/MAX.II with carboxypeptidase M (CPM), a phosphoinositol
      linked endopeptidase, was recently described. CPM is able to process a multitude
      of different substrates, among them immunologically important peptides such as
      bradykinin, anaphylatoxins and enkephalins. It was previously shown to be
      expressed in placenta, lung and kidney. CPM as detected by MAX.I/II shows a
      strong expression on MO-derived MAC in vitro and on MAC in vivo accompanying T
      lymphocyte activation such as during allogeneic transplant rejection or allergic
      alveolitis. In contrast, its expression is suppressed on MAC by some types of
      tumor cells. A synchronous expression of CPM together with MAC cytotoxic function
      makes a functional relationship very well possible. However, the biological
      importance of CPM expression on MAC in vivo is difficult to predict, since a wide
      range of biologically active peptides are substrates for CPM, and the relevance
      for most of those peptides to be processed by CPM during an immune reaction is
      only poorly understood at present.

PMID- 9553770
TI  - Cellular carboxypeptidases.
AB  - This article focuses on four human carboxypeptidases (CPs): two metallo-CPs and
      two serine CPs. The metallo-CPs are members of the so-called B-type regulatory CP
      family, as they cleave only the C-terminal basic amino acids Arg or Lys. The
      plasma membrane-bound CPM and the mainly, but not exclusively, intracellular CPD
      are surveyed from this group of enzymes. These enzymes can regulate peptide
      hormone activity at the cell surface and possibly intracellularly after receptor
      mediated endocytosis and may also participate in peptide hormone processing. The
      serine CPs, as their name indicates, contain a serine residue in the active
      center essential for catalytic activity that reacts with organophosphorus
      inhibitors. Prolylcarboxypeptidase (PRCP) (angiotensinase C) and deamidase
      (cathepsin A, lysosomal protective protein) are discussed here. These two enzymes
      are highly concentrated in lysosomes; however, they may also be active
      extracellularly after their release from lysosomes in soluble form or in a plasma
      membrane-bound complex. Whereas deamidase cleaves a variety of peptides with C
      terminal or penultimate hydrophobic residues (e.g. substance P, angiotensin I,
      bradykinin, endothelin, fMet-Leu-Phe). PRCP cleaves only peptides with a
      penultimate Pro residue (e.g. des-Arg9-bradykinin, angiotensin II). These enzymes
      may also be involved in terminating signal transduction by inactivating peptide
      ligands after receptor endocytosis.

PMID- 9553771
TI  - Deciphering the apoptotic pathway: all roads lead to death.
AB  - Research into apoptosis is proceeding at such a fast and ferocious pace that
      anyone who is not completely engrossed in the field has difficulty keeping track
      of the constant stream of newly identified proteins involved in the process.
      Apart from being an enticing concept, the process of cell suicide is an important
      function with wide-reaching implications. Virologists, biologists, immunologists,
      physiologists and oncologists alike have had to incorporate this phenomenon into
      their disciplines. The purpose of this article is to provide a solid background
      on which to further review recent advances in this exciting field. The Bcl-2 and
      caspase family homologues are discussed in detail and various models are proposed
      to explain how they function to regulate and execute the death programme.
      Finally, the importance of programmed cell death with respect to immune function
      is explored, emphasizing the targets of viral inhibitors of apoptosis.

PMID- 9553772
TI  - Tumour surveillance: missing peptides and MHC molecules.
AB  - Immunotherapy involving CTL is an attractive alternative for treatment of various
      malignancies. One of the approaches currently being explored for immune targeting
      of human cancers involves potentiation of immunogenicity of malignant cells by
      gene transduction. This strategy is undoubtedly influenced by the ability of the
      malignant cells to endogenously process and present target epitopes on their cell
      surface for immune recognition by CTL. However, there is increasing evidence to
      suggest that a large proportion of human cancers escape CTL-mediated immune
      surveillance by selectively down-regulating the expression of MHC class I
      molecules and peptide transporter genes. Understanding and molecular analysis of
      these immunologically relevant genetic defects in tumours is very important
      before translating preclinical studies of immunotherapy to rational clinical
      trials. Careful consideration of these potential limitations may lead to the
      development of novel immunotherapeutic strategies and, potentially, prevention of
      tumour progression or development.

PMID- 9553773
TI  - Second symmetry in the BALB/c-C57BL/6 (B6) system, and anti-antiself antibodies
      in ageing B6 mice.
AB  - Using an ELISA assay and inhibition of antibody mediated cytotoxicity we found
      that there was a higher level of anti-antiself activity in B6 anti-BALB/c
      alloimmune mice than in BALB/c anti-B6 mice. In contrast, when an inhibition of
      cellular cytotoxicity assay was used to assay for the activity, similar levels of
      anti-antiself antibodies were seen in B6 anti-BALB/c and BALB/c anti-B6 sera.
      Anti-antiself antibodies in alloimmune sera are not absorbed by the cellular
      immunogen as readily as are anti-foreign antibodies. These results are
      interpreted in terms of anti-antiself antibodies being directed mainly against T
      cell receptors specific for self. Anti-antiself antibodies are found also in old
      B6 mice, that are also known to make autoantibodies.

PMID- 9553774
TI  - Defective TCR expression in transgenic mice constructed using cDNA-based alpha-
      and beta-chain genes under the control of heterologous regulatory elements.
AB  - We describe the generation of ovalbumin (OVA)-specific, MHC class II-restricted
      alpha beta T cell receptor (TCR) transgenic mice. Initial attempts at generating
      these transgenic mice utilized heterologous regulatory elements to drive the
      expression of cDNA genes encoding the separate alpha- and beta-chains of the TCR.
      Unexpectedly, T cells bearing the transgenic alpha beta TCR failed to emerge from
      the thymus in these mice, although the transgenes did modify endogenous TCR
      expression. However, subsequent modification of the approach which enabled
      expression of the TCR beta-chain under the control of its natural regulatory
      elements generated mice whose peripheral T cells expressed the transgenic TCR and
      were capable of antigen-dependent proliferation. These results show that
      successful generation of MHC class II-restricted, OVA-specific alpha beta TCR
      transgenic mice was dependent upon combining cDNA- and genomic DNA-based
      constructs for expression of the respective alpha- and beta-chains of the TCR.

PMID- 9553775
TI  - IL-4, IL-5 and IL-10 are not required for the control of M. bovis-BCG infection
      in mice.
AB  - Mycobacterial infections in mice are normally characterized by a profound Th1
      cell-mediated immune response, in which T cells secrete large amounts of IFN
      gamma. Recent evidence suggests that this response also includes a Th2 component.
      In order to investigate whether production of IL-4, IL-5, or IL-10 influenced the
      outcome of a Mycobacterium bovis-bacille Calmette-Guerin (BCG) infection, we
      intranasally infected IL-4, IL-5, and IL-10 gene-deficient and control mice and
      monitored the resulting immune response and bacterial clearance. IL-4, IL-5, and
      IL-10 deficient mice cleared the mycobacteria with the same kinetics as control
      mice. Furthermore, T cells of cytokine deficient and control mice produced
      similar levels of IFN-gamma following in vitro stimulation with purified protein
      derivative (PPD) from M. bovis. We conclude that the cytokines IL-4, IL-5 and IL
      10 are not essential for and do not negatively influence the protective immune
      response against M. bovis-BCG in the lung of mice.

PMID- 9553776
TI  - Insights into the aetiology and pathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system, and the most common neurological disease affecting young adults.
      Multiple sclerosis is a clinically heterogeneous disorder. It is believed to be
      an autoimmune disease, with cell-mediated and humoral responses directed against
      myelin proteins. This hypothesis largely comes from pathological parallels with
      an animal model, experimental autoimmune encephalomyelitis (EAE). Autoimmunity to
      myelin proteins in humans may be inadvertently triggered by microbes which have
      structural homologies with myelin antigens (molecular mimicry). As with other
      autoimmune diseases, susceptibility to MS is associated with certain MHC
      genes/haplotypes. Full genomic screening of mutiplex families has underscored the
      role for MHC genes as exerting moderate but the most significant effects in
      susceptibility. The primary target autoantigen in MS has yet to be definitively
      identified, but as well as the major myelin proteins, it is now clear that minor
      myelin components, such as myelin oligodendrocyte glycoprotein (MOG) may play a
      primary role in disease initiation. This review examines the current knowledge
      about the aetiology and pathogenesis of MS, and the important similarities with
      EAE. A better understanding of the molecular mechanisms of autoimmune pathology
      will provide the basis for more rational immunotherapies to treat MS.

PMID- 9553777
TI  - Current immunotherapy in multiple sclerosis.
AB  - The underlying pathophysiology of multiple sclerosis is presumed to be autoimmune
      in nature. Attempts to find an effective treatment for this common disease of the
      central nervous system have primarily focused on immune-mediated therapies, both
      immunosuppressive and immunomodulatory. The wide variety of immunological
      abnormalities detected in multiple sclerosis and its animal model, experimental
      allergic encephalomyelitis, has prompted the testing of a diverse array of drugs
      to be used for treatment. Recent successes in the treatment of relapsing
      remitting multiple sclerosis with interferon beta and glatiramer acetate have
      renewed interest in and raised expectations for the effective control of this
      neurological disorder. Improved methodology in clinical trials, the development
      of surrogate markers and the availability of novel therapies bode well for more
      rapid advances.

PMID- 9553778
TI  - Cytokine-directed therapies in multiple sclerosis and experimental autoimmune
      encephalomyelitis.
AB  - Secreted and cell surface molecules that control the nature of immune responses
      or directly mediate tissue damage are important targets for therapeutic
      intervention of autoimmune inflammatory disorders. The precise aetiology of
      multiple sclerosis (MS), an inflammatory demyelinating disease of the central
      nervous system is unknown and therapeutic interventions for this disease are
      limited. However, as it is believed that MS is autoimmune in nature, it seems
      likely that targeting of the immune system, either to deviate it down a more
      benign pathway or to directly block tissue damaging effector mechanisms, may
      enable this disease to be controlled. In this overview we examine three
      alternative approaches to therapy of MS: cytokine-directed immune deviation,
      immunoregulation by type I interferons and blockade of TNF. Underlying rationales
      for the application of these approaches to the treatment of MS are based largely
      on studies in the disease model experimental autoimmune encephalomyelitis. These
      studies are reviewed.

PMID- 9553779
TI  - Oral tolerance as therapy for experimental autoimmune encephalomyelitis and
      multiple sclerosis: demonstration of T cell anergy.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an important model for
      developing therapies for multiple sclerosis (MS). The oral administration of the
      central nervous system antigen, myelin basic protein (MBP), to Lewis rats and
      susceptible mouse strains prior to MBP immunization prevents the induction of
      EAE. Clinical trials administering myelin orally to MS patients have met with
      only partial success, and thus require that oral tolerance be further studied to
      improve this treatment strategy. Clonal anergy, clonal deletion, immune deviation
      from Th1 to Th2 T cell subsets, and active suppression by TGF-beta-secreting T
      cells have all been implicated as possible mechanisms in oral tolerance. Which
      mechanism predominates depends on antigen dosage, frequency of feeding, and
      timing of antigen administration. In this study, we have characterized T cells
      derived from MBP-fed rats and determined the level of their unresponsiveness.
      Myelin basic protein-specific T cells are indeed present although in reduced
      numbers in lymphoid tissue of orally tolerized animals. Following several cell
      divisions in the presence of IL-2, these MBP-specific T cells undergo a dramatic
      reversal of unresponsiveness, proliferate in response to MBP and are capable of
      transferring EAE. These results support clonal anergy as an important mechanism
      for oral tolerance. Recent developments in clinical trials of oral tolerance are
      described.

PMID- 9553780
TI  - Effects of vaccination with T cell receptor peptides: epitope switching to a
      possible disease-protective determinant of myelin basic protein that is cross
      reactive with a TCR BV peptide.
AB  - Immunization of Lewis rats with guinea-pig myelin basic protein (Gp-MBP) induced
      T cell responses to primary and secondary encephalitogenic determinants, as well
      as to a third non-encephalitogenic epitope, residues 55-69. This sequence is of
      interest due to its protective activity against experimental autoimmune
      encephalomyelitis. Protection involved induction of MBP-55-69-specific T cells
      expressing cross-reactive TCR BV8S6 genes that activated regulatory T cells
      specific for TCR BV8S2 determinants expressed on encephalitogenic T cells. We
      here present and discuss new evidence suggesting a possible immunological cross
      reactivity between the protective Gp-MBP-55-69 peptide and the regulatory BV8S2
      39-59 peptide. This cross-reactivity, which may also occur between the human MBP
      55-74 peptide and the BV12S2-38-58 sequence, has potentially important
      implications for human diseases such as multiple sclerosis.

PMID- 9553781
TI  - Approaches to the treatment of central nervous system autoimmune disease using
      specific neuroantigen.
AB  - The ultimate aim in the treatment of autoimmune disease is to restore self
      tolerance to the autoantigen(s) in question. In lieu of this ideal result, the
      conversion of a destructive or pathogenic autoimmune response into one of benign
      autoimmunity would also be highly desirable. In either case the use of the
      antigenic epitope, which is the target of the destructive immune response, would
      ideally be employed so as to give specificity to the protection without the need
      for long-term immunosuppression. This review describes a number of different
      approaches using various forms, doses, and routes of injection of specific
      neuroantigen to inhibit the different clinical varieties of autoimmune
      encephalomyelitis in a number of animal models; all done with the view to
      translating the findings into the clinic for the treatment of multiple sclerosis.
      We conclude that any treatment strategy for multiple sclerosis (MS) must have a
      number of features: it must be clinically acceptable, specific, long-lasting,
      require only short-term treatment, able to shunt off ongoing disease, and have
      the potential to prevent or deal with epitope spreading. Few of the approaches we
      describe fulfill all of these criteria. We suggest that investigations of new
      adjunctive agents to be used with a specific antigen be pursued, and that
      currently the use of chimeric proteins or DNA vaccination with or without the new
      adjunctives may hold the most hope for the future.

PMID- 9553782
TI  - Treatment of central nervous system inflammation with inhibitors of basement
      membrane degradation.
AB  - Currently available anti-inflammatory drugs for the treatment of multiple
      sclerosis (MS) and other inflammatory diseases are generally inadequate, with
      disease progression not being arrested by the treatments and undesirable side
      effects posing problems. In response to these deficiencies our laboratories have,
      over the past 10 years, been developing novel drugs that interfere with the entry
      of leucocytes into inflammatory sites by inhibiting their passage through the
      subendothelial basement membrane (BM). This review initially summarizes evidence
      supporting the hypothesis that the subendothelial BM is a major barrier to the
      accumulation of leucocytes in inflammatory sites. An important point that has
      emerged is that breaching of the BM is probably a cooperative process, involving
      activation- and cytokine-induced degradative enzymes contributed by leucocytes,
      endothelial cells and platelets. The review then discusses the properties of
      three separate classes of anti-inflammatory compounds we have developed, namely
      sulfated polysaccharides/oligosaccharides, phosphosugars, and castanospermine
      (CS), which inhibit the passage of leukocytes through BM. Each drug type appears
      to prevent BM degradation by a different mechanism. Sulfated
      polysaccharides/oligosaccharides mediate their anti-inflammatory effect by
      inhibiting the endoglycosidase, heparanase, which plays a key role in the
      solubilization of BM by invading leucocytes. In fact, our studies have
      highlighted the heparanase enzyme as a major target for future drug development.
      Phosphosugars probably inhibit inflammation by displacing lysosomal enzymes,
      which are involved in BM degradation, from cell surface mannose 6-phosphate
      receptors. This mechanism of expressing degradative enzymes on the cell surface
      is particularly evident with activated T lymphocytes. On the other hand, CS
      interferes with appropriate targeting of lysosomal enzymes involved in BM
      degradation. For reasons which are still unclear, CS specifically inhibits BM
      degradation by endothelial cells, which results in a characteristic perivascular
      arrest of leucocytes in inflammatory sites. Overall, our studies have established
      that inhibitors of subendothelial BM degradation represent viable anti
      inflammatory agents. It is hoped that future work will result in the development
      of a totally new class of highly effective, subtle and non-toxic anti
      inflammatory drugs for the treatment of MS and other inflammatory diseases.

PMID- 9553783
TI  - Occupational medicine in China.

PMID- 9553784
TI  - Exposure to carbon black: a cancer risk?
AB  - Lung cancer is one of the most serious health problems in the industrial nations
      and is therefore of great public and scientific interest. Although inhalative
      cigarette smoking is without doubt the main cause for the increasing frequency of
      lung cancer, during recent years there has been more and more public interest in
      other substances in the environment or at the work place that are assumed to be
      potentially carcinogenic especially due to experiences with fibrous particles
      such as asbestos and their effects. Enhanced attention is also directed to inert
      or nuisance dusts such as carbon black. Evaluation of the possibly increased risk
      for humans should first be based on exact epidemiology data. In the absence of
      those data--as in the case of carbon black--experimental data in animals serve as
      the point of orientation, especially results gained in rats in long-term
      inhalation studies. Pathologic anatomy investigations of human lungs under
      similar exposure conditions, however, render results quite different from those
      obtained in rats and, thus, preclude ready interpretation of animal results to
      human risk assessment. This is particularly true for the development of lung
      tumors in rats under overload conditions as well as for certain tumor types not
      observed in human lung tissues. It is therefore quite understandable that many
      researchers propose to interpret the changes observed in rat lung tissues after
      inhalation of carbon black as rat-specific reaction mechanisms that cannot be
      applied to human tissues, which in the past have led to the wrong conclusions
      regarding human risk assessment due, among other factors, to incorrect
      experimental design and inaccurate nomenclature of tumorous lesions in rats.

PMID- 9553785
TI  - Urinary 2,5-hexanedione increases with potentiation of neurotoxicity in chronic
      coexposure to n-hexane and methyl ethyl ketone.
AB  - OBJECTIVE: MEK (methyl ethyl ketone) is widely and frequently used as an
      ingredient of mixed solvents together with n-hexane. MEK is known to decrease
      urinary levels of 2,5-hexanedione dose-dependently in an acute or chronic
      coexposure with a constant level of n-hexane. This change in urinary 2,5
      hexanedione appears to contradict the potentiation effect of MEK on n-hexane
      induced neurotoxicity because it is believed that the toxicity of n-hexane is
      activated through n-hexane metabolism. We aimed to clarify how the urinary level
      of 2,5-hexanedione changes when MEK modifies the degree of n-hexane-induced
      neurotoxicity. METHOD: A total of 32 male Wistar rats were divided into 4 groups
      of 8 each and were then exposed to fresh air only, 2000 ppm n-hexane only, 2000
      ppm n-hexane plus 200 ppm MEK, and 2000 ppm n-hexane plus 2000 ppm MEK,
      respectively. Inhalation exposures were performed 12 h/day, 6 days/week, for 20
      weeks. Motornerve conduction velocity (MCV), distal latency (DL), and urinary 2,5
      hexanedione were measured every 4 weeks. RESULTS: The MCV decreased, the DL
      increased, and urinary levels of 2,5-hexanedione increased in the 2000-ppm n
      hexane plus 200 ppm MEK group in comparison with the 2000-ppm n-hexane only group
      following 4 weeks' exposure. On the 1st day of exposure, however, coexposure to
      MEK decreased urinary levels of 2,5-hexanedione dose-dependently. CONCLUSIONS:
      The present study showed that urinary concentrations of 2,5-hexanedione increased
      with potentiation of n-hexane neurotoxicity. Urinary 2,5-hexanedione
      concentration does not necessarily reflect the exposure concentration of n-hexane
      in coexposure to n-hexane along with MEK or other solvents, but it may be useful
      as a marker in the assessment of neurotoxicity in coexposure to n-hexane and
      other solvents.

PMID- 9553786
TI  - Variation in the ratio of respirable particulates over inhalable particulates by
      type of dust workplace.
AB  - OBJECTIVE: The aim of the present study was to clarify the quantitative
      relationship between respirable particulates and inhalable particulates in
      various dust workplaces. METHODS: Both respirable particulate and inhalable
      particulate concentrations were measured in 1644 dust workplaces by means of
      elutriation, and the ratio of respirable particulate mass over that of inhalable
      particulate (R/I ratio) was calculated for each workplace. RESULTS: Statistical
      analyses showed that the R/I ratio varied substantially, depending on the type of
      dust work. The ratio was highest in welding workplaces (mean +/- SD: 53 +/- 19%)
      and lowest in foundries (23 +/- 16%); the former value suggests that respirable
      particulate exposure may be underestimated in substantial parts of welding work
      when only the occupational exposure limit for inhalable particulates is taken for
      compliance testing. CONCLUSIONS: Simple compliance with the limit for inhalable
      particulates is not sufficient, and the limit for respirable particulates should
      also be simultaneously cleared.

PMID- 9553787
TI  - Correspondence between occupational exposure limit and biological action level
      values for alkoxyethanols and their acetates.
AB  - OBJECTIVES: The Finnish occupational exposure limit (OEL) values for
      alkoxyethanols and their acetates were lowered in 1996. A reevaluation of the
      correspondence between the new OEL value and the biological action level (BAL)
      was thus needed. This study was conducted in silkscreen printing enterprises,
      where 2-alkoxyethanols and their acetates are mainly used as solvents. The
      air/urine correlations between 2-methoxyethylacetate, 2-ethoxyethylacetate, 2
      butoxyethanol, 2-butoxyethylacetate, and 2-methoxyacetic (MAA), 2-ethoxyacetic
      (EAA), and 2-butoxyacetic acid (BAA) were evaluated on an individual and time
      related basis at four different enterprises. METHODS: Inhalation exposure to
      alkoxyalcohols and their acetates was monitored with diffusion badges (n = 38)
      for an entire work week. Urinary excretion of alkoxyacetic acids immediatley
      after the shift and at 14-16 h after exposure (n = 112) was analyzed by a gas
      chromatograph equipped with a flame-ionization detector. RESULTS: Inhalation
      exposure to 2-methoxyethylacetate at 0.5 cm3/m3 corresponded to MAA excretion of
      3 mmol/mol creatinine in urine at 14 to 16 hours after exposure. The next-morning
      urinary EAA excretion of 37 mmol/mol creatinine corresponded to an 8-h 2
      ethoxyethylacetate exposure of 2 cm3/m3 when all collected data were included.
      This average EAA excretion was 69% of the German BAT value and only 34% of the
      American biological exposure index (BEI) value. Urinary EAA excretion was 30-40%
      lower at the beginning of the work week than at the end of the work week. On the
      other hand, EAA excretion was 10-20% higher than that measured at 14-16 h after
      exposure. Urinary BAA excretion of 75 mmol/mol creatinine in postshift urine
      corresponded to an 8-h 2-butoxyethanol and 2-butoxyethylacetate exposure of 5
      cm3/m3. This BAA excretion was 87% of the German BAT value. CONCLUSION: According
      to these results, it seems that the BAL for MAA and EAA should be 3 and 50
      mmol/mol creatinine as measured at 14-16 h after exposure, respectively. The BAL
      value for BAA seems to be 70 mmol/mol creatinine in postshift samples. These
      recommendations are valid only if samples are collected at the end of the work
      week.

PMID- 9553788
TI  - Mortality by cancer in groups of the Belgian population with a moderately
      increased intake of arsenic.
AB  - OBJECT: The dose-response relationship for lung carcinoma and other cancers at
      low doses of As is highly uncertain because it is based on modeling data
      collected in populations with a high daily intake of the element. The finding of
      a slightly increased exposure to arsenic in certain groups of the Belgian general
      population prompted us to examine whether this had repercussions on the causes of
      mortality. METHOD: Statistics of mortality by causes with a possible link to
      exposure to the element (standardized mortality ratio) were analyzed in groups of
      the Belgian population previously shown to have been exposed to As from natural
      (drinking water) and/or industrial (nonferrous metal smelter emissions) sources.
      RESULTS: A moderately increased absorption of As, leading to a 3- to 4- fold
      higher urinary excretion (35 micrograms/day as compared with 6-10 micrograms
      As/day in nonexposed subjects) did not enhance the mortality by diseases of the
      nervous system, liver and heart, and cancers. An increase in mortality by lung
      cancer, however, was observed in men but not women living around zinc smelters
      and might be related to past occupational exposure and/or smoking habits.
      CONCLUSION: A low to moderate level of environmental exposure to inorganic
      arsenic (0.3 microgram As/m3 of air; 20-50 micrograms As/l of drinking water)
      does not seem to affect the causes of mortality, suggesting in particular
      nonlinearity of the dose-response relationship for arsenic and cancer.

PMID- 9553789
TI  - Longitudinal changes in inflammatory markers in nasal lavage of cotton workers.
      Relation to endotoxin exposure and lung function changes.
AB  - OBJECTIVES: The aim of this study was to evaluate time-related changes in
      inflammatory markers in nasal lavage (NAL) in relation to endotoxin exposure and
      lung function changes. METHODS: Endotoxin in cotton dust is well known to elicit
      proinflammatory mediators involved in acute or chronic respiratory inflammation
      due to cotton dust. We applied nasal lavage as well as lung function and exposure
      measurements in a small group (n = 11) of cotton workers during 6 weeks of
      observation (after 2 weeks free of exposure). Several inflammatory markers in
      NAL, such as interleukin 8 (IL-8), IL-6, and down-stream mediators, including
      soluble tumor necrosis factor receptor 75 (sTNF-R75) and soluble intercellular
      adhesion molecule 1 (ICAM-1), cell counts, marker of epithelial response (uric
      acid), and marker of plasma exudation (albumin) were measured. RESULTS: At the
      exposure levels examined in this study [cotton dust, geometric mean (GM) = 1.10
      mg/m3; endotoxin, GM = 2,869 EU/m3], several inflammatory markers in NAL such as
      IL-8, sTNF-R75, and albumin tended to increase through the measurement period
      with increasing airborne endotoxin concentration (in six workers who had paired
      measurements in weeks 1 and 6). Although no statistical significance was reached,
      airborne endotoxin exposure and all inflammatory markers in NAL were relatively
      higher in cotton workers with a 6-week lung function decrease. CONCLUSION: The
      data suggest that inflammatory markers in NAL are associated with repeated
      airborne endotoxin exposure.

PMID- 9553790
TI  - Sister chromatid exchanges in rotogravure printing plant workers.
AB  - OBJECTIVE: The individual burden of inhaled ambient-air toluene and its link to
      genotoxic phenomena in exposed printing workers. METHOD: The influence of toluene
      on sister chromatid exchange (SCE) was investigated by monitoring of the
      individual toluene burden of 42 exposed printing workers. Therefore, the urinary
      hippuric acid (HA) excretion was measured directly after the work shift. The
      results were compared with those recorded for a control group consisting of 45
      blood donors. SCE frequencies were determined from peripheral lymphocytes for
      both groups. RESULTS: The median HA excretion of the exposed and nonexposed
      groups amounted to 1.94 and 0.45 g/g creatinine, respectively. For both groups,
      different SCE rates were detected: 10.13 and 6.84 counts/lymphocyte for exposed
      and nonexposed persons, respectively. The independence of the measured values
      proved to be significant at a high confidence level (P = 0.000) for both groups.
      The influences of smoking and alcohol consumption on SCE as well as on HA values
      could be clearly separated from those induced by toluene. CONCLUSIONS: The
      results of our study indicate a strong relationship between the individual
      toluene burden and the genotoxic risk of the exposed persons. Since toluene was
      used for dilution of the letter-press ink, the influence of ink mist on the
      genotoxic effects could not be completely excluded.

PMID- 9553791
TI  - Exposure of gasoline road-tanker drivers to methyl tert-butyl ether and methyl
      tert-amyl ether.
AB  - Organic oxygenates, namely, methyl tert-butyl ether (MTBE) and methyl tert-amyl
      ether (MTAE), are added to gasoline to reduce carbon monoxide in exhausts and to
      enhance the octane number. The aim of this study was to investigate road-tanker
      drivers' exposure to oxygenate vapors during road-tanker loading and unloading as
      well as to evaluate the measurements of these ethers and their metabolites in the
      urine as a means of assessing the uptake of the ethers. A total of 11 drivers in
      different parts of Finland were trained to monitor their exposure with personal
      samplers, to report their working conditions, and to collect their whole-day
      urine samples. Charcoal tubes of the air samples were analyzed for MTBE, MTAE,
      benzene, toluene, and aliphatic hydrocarbons. For biological monitoring purposes
      the two main oxygenates, tertiary ethers MTBE and MTAE, as well as their main
      metabolites, tertiary alcohols tert-butanol (TBA) and tert-amyl alcohol (TAA),
      were determined in urine specimens. On average the drivers were exposed to vapors
      for short periods (21 +/- 14 min) three times during a work shift. The mean
      concentrations of MTBE and MTAE (mean +/- SD) were 8.1 +/- 8.4 and 0.3 +/- 0.4
      mg/m3. The total MTBE uptake during the shift was calculated to be an average of
      106 +/- 65 mumol. The mean concentrations of MTBE, TBA, MTAE and TAA detected in
      the first urine after the work shift were 113 +/- 76, 461 +/- 337, 16 +/- 21, and
      40 +/- 38 nmol/l, and those found the next morning, 16 h later, were 18 +/- 12,
      322 +/- 213, 9 +/- 10, and 20 +/- 27 nmol/l. The good relationship (r = 0.84)
      found between MTBE exposure and postshift excretion suggests that urinary MTBE
      can be used for biological monitoring of exposure, but at the present low level
      of exposure the corresponding metabolite TBA is not equally reliable. The
      determination of MTAE and its metabolite TAA in urine is sensitive enough to
      detect the low degree of exposure to MTAE, but in this study the data were too
      scarce to allow calculation of the correlations due to very low levels of MTAE
      exposure.

PMID- 9553792
TI  - Occupational lead exposure and screening of glucose-6-phosphate dehydrogenase
      polymorphism: useful prevention or nonvoluntary discrimination?
AB  - OBJECTIVE: To discuss regulatory guidelines excluding subjects with erythrocyte
      glucose-6-phosphate dehydrogenase (G6PD) deficiency from lead-exposed jobs in the
      light of epidemiology findings on the mortality of these subjects. METHODS: Two
      mortality follow-up studies were conducted. The first comprised 1979 male
      subjects newly identified as G6PD-deficient during a 1981 screening of the G6PD
      polymorphism among the general population in Sardinia, Italy. The second
      comprised 1080 male workers employed in maintenance and production departments of
      a lead smelting plant, who were divided into two subcohorts by erythrocyte G6PD
      phenotype. RESULTS: As compared with the general male population, G6PD-deficient
      subjects had significantly fewer deaths than expected from ischemic heart disease
      (standardized mortality ratio (SMR) = 28; 95% CI 10-62), cerebrovascular diseases
      (SMR = 22; 95% CI 6-55), and liver cirrhosis (SMR = 12; 95% CI 0-66). Among lead
      smelters the standardized mortality rates from cardiovascular diseases and all
      cancers observed among the G6PD-deficient subcohort were lower than those seen
      among subjects with the wild-type G6PD. No death from disease of the blood and
      hematopoietic system was observed among G6PD-deficient subjects in these two
      follow-up studies. CONCLUSIONS: These studies did not provide evidence of
      hypersensitivity to lead hematotoxicity among G6PD-deficient individuals at
      exposure levels within the current standards. Provided that workplace exposure
      complies with current standards, the hypothetical benefit of excluding G6PD
      deficient individuals from lead-exposed jobs should be weighted against the loss
      of personal abilities and the economic damage in a social environment with
      diffuse unemployment.

PMID- 9553793
TI  - The Service for the Organization of Postexposure Medical Examinations: ODIN.
AB  - In Germany, occupational contact with carcinogenic substances is regulated by
      very strict legislation. Thus, alongside strict implementation of agreement 139
      of the International Labour Organization (ILO), legislation governing the medical
      monitoring and care of employees in the form of specialist preventive medical
      examinations is also in force. It is extremely important that medical preventive
      care should continue after employment involving contact with carcinogenic
      substances has ceased, since there is often a long delay before occupationally
      induced carcinosis develops. The German Service for the Organization of
      Postexposure Medical Examinations (ODIN) was established by the statutory German
      accident insurance institutions to ensure that early detection examinations
      continue to be performed into the employee's later life. Such preventive
      examinations can significantly enhance the success of cancer treatment by
      detecting malignancy in its early stages. The registration by ODIN of data
      concerning exposure to hazardous substances also has the function of preserving
      evidence required for possible compensation claims by victims of occupational
      illnesses. In the longer term, ODIN data may help us to explain the relationship
      between exposure to hazardous substances and the incidence of carcinosis.

PMID- 9553795
TI  - Predictive modelling of inactivation of Listeria spp. in bovine milk during high
      temperature short-time pasteurization.
AB  - A linear model was derived to describe the thermal inactivation of Listeria
      innocua in bovine whole milk in a high-temperature short-time pilot scale
      pasteurizer. Integrated lethal effect, or pasteurization effect (PE), was
      obtained by converting times at different temperatures in the various sections of
      the pasteurizer to the equivalent time at the reference temperature (72 degrees
      C). PE was then related by a simple linear function to the log10 of the % viable
      counts with a power transformation of the PE values to improve the linear fit. R2
      values for the five L. innocua trials varied from 0.728 to 0.974. Validation of
      this model with Listeria monocytogenes confirmed that L. monocytogenes was more
      heat sensitive. Inter-trial variation was incorporated into the model using the
      @RISK simulation software. Output from simulations confirmed that pasteurization
      at the IDF standard conditions of 72 degrees C for 15 sec can ensure at least an
      11-log reduction of L. monocytogenes. The results showed that L. innocua may be
      used as a model microorganism to assess the thermal inactivation of L.
      monocytogenes, since its heat resistance is at least equal to or greater than
      that of the pathogenic species.

PMID- 9553794
TI  - Evaluation of the role of Carnobacterium piscicola in spoilage of vacuum- and
      modified-atmosphere-packed cold-smoked salmon stored at 5 degrees C.
AB  - The microflora on spoiled cold-smoked salmon often consists of a mixture of
      lactic acid bacteria (LAB) and Gram-negative bacteria. To elucidate the role of
      the different groups, a storage trial was carried out in which nisin and CO2 were
      used for the selective inhibition of the two bacterial groups. The shelf-life of
      vacuum-packed cold-smoked salmon, recorded by sensory evaluation, was four weeks
      at 5 degrees C and the microflora was composed of LAB (10(6)-10(7) cfu/g) with an
      associate Gram-negative flora in varying levels (10(5)-10(7) cfu/g). The addition
      of nisin and/or a CO2-atmosphere increased the shelf-life to five or six weeks
      and limited the level of LAB to about 10(4)-10(6), 10(3)-10(6) and 10(2)-10(4)
      cfu/g, respectively. CO2-atmosphere +/- nisin inhibited the growth of Gram
      negative bacteria, whereas nisin had no effect on these in vacuum packages. The
      Gram-negative flora on vacuum-packed salmon was dominated by a Vibrio sp.,
      resembling V. marinus, Enterobacteriaceae (Enterobacter agglomerans, Serratia
      liquefaciens and Rahnella aquatilis) and occasionally Aeromonas hydrophila.
      Irrespective of the addition of nisin and/or CO2-atmosphere, the LAB microflora
      was dominated by Carnobacterium piscicola, which was found to account for 87% of
      the 255 LAB isolates characterized. Whole-cell-protein patterns analysed by SDS
      PAGE confirmed the Carnobacterium species identification. The spoilage potential
      of C. piscicola isolates was further studied by inoculation of approx. 10(6)
      cfu/g in cold-smoked salmon stored at 5 degrees C. The salmon did not spoil
      within 4 weeks of storage in vacuum- or CO2-atmosphere, and it is concluded that
      despite high levels (> 10(7) cfu/g) of C. piscicola, sensory rejection was caused
      by autolytic changes. This was supported by the development of soft texture and
      sour, rancid and bitter off-flavours at the point of spoilage, irrespective of
      the length of shelf-life and low or high total counts of LAB and Gram-negative
      bacteria.

PMID- 9553796
TI  - Interaction of monolaurin, eugenol and sodium citrate on growth of common meat
      spoilage and pathogenic organisms.
AB  - Interactions of monolaurin, eugenol (phenolic compound) and sodium citrate
      (chelator) on the growth of six organisms including common meat spoilage
      (Lactobacillus curvatus, Lactobacillus sake, Leuconostoc mesenteroides,
      Brochothrix thermosphacta) and pathogenic (Escherichia coli O157:H7 and Listeria
      monocytogenes) organisms were investigated. The combinations of 100 to 250 ppm
      monolaurin with 500 and 1000 ppm eugenol, and 0.2 and 0.4% sodium citrate were
      more effective than each component separately. More than one combination
      prevented detectable growth of each organism. Lactic acid bacteria (LAB) and E.
      coli O157:H7 were most resistant and L. monocytogenes and B. thermosphacta most
      sensitive to control by the chosen combinations. The presence of sodium citrate
      was necessary to yield potent inhibition of Lb. curvatus and Lb. sake growth by
      the monolaurin and eugenol combinations.

PMID- 9553797
TI  - Identification of pseudomonads from fresh and chill-stored chicken carcasses.
AB  - Results of carbon source assimilation tests (17 carbon compounds) led to 88% of
      pseudomonads from cold-stored chicken carcasses being assigned to one of 17
      groups. Of these groups, 13 had combinations of properties identical to, or with
      readily recognizable degrees of similarity to those of published species/biovars.
      Two of the four groups having carbon assimilation patterns dissimilar to any
      known species had cellular fatty acid composition corresponding to Pseudomonas
      fluorescens, and two to Pseudomonas lundensis or Pseudomonas fragi. The P.
      fluorescens biovars all had higher amounts of 16:1 cis 9 (21-37%) and 18:1 cis 11
      (10-19%), than of 17:0 cyclo (1-17%) and 19:0 cyclo (0-1%). In contrast, for P.
      lundensis and P. fragi, the relative amounts of these unsaturated acids and
      cyclopropane acids were reversed. Both the carbon source assimilation tests and
      the cellular fatty acid composition led to the conclusion that none of the
      species were dominant, although the P. fluorescens biovars constituted about 50%
      of the isolated pseudomonads.

PMID- 9553798
TI  - Rapid cooling, moderate heat treatment and nisin addition influence cell
      homeostasis of Clostridium perfringens type A.
AB  - Vegetative cells of Clostridium perfringens type A were exposed to heat shock (50
      degrees C), cold shock (4 degrees C) and nisin, respectively. In all cases,
      pronounced leaks of cellular K+ were observed. These losses were not
      systematically related to cell death, as demonstrated by cell viability
      measurement by the most probably number method. During heat shock treatment, a
      90% decrease of initial population was measured within 15 min, and K+ leaks were
      mainly associated to cell death. A cold shock induced a rapid and large K+ efflux
      from the cells, at least 50% of the total potassium content. Potassium movements
      were not associated with internal pH changes, or with cell death during cooling
      at 4 degrees C. After nisin addition up to 70% of the cellular potassium was lost
      within 5 min. These potassium losses led to a transmembrane pH gradient decrease,
      but not to cell death at 50 IU ml-1 of nisin. Increasing the nisin concentration
      to 200 IU ml-1 resulted in a decimal reduction of 2.62.

PMID- 9553799
TI  - Characterization of Bifidobacterium strains for use in soymilk fermentation.
AB  - Soybean milk, which serves as a base for a variety of beverages, contains
      raffinose, stachyose, pentanal and n-hexanal; the former two may be responsible
      for flatulence after fermentation, whilst the latter two for a beany flavour.
      Twenty-seven strains of Bifidobacterium were analyzed for their alpha
      galactosidase activity and the production of lactic and acetic acids to determine
      their potential for use in the production of fermented soymilk. The behaviour of
      three strains in soymilk was studied to determine their ability to reduce alpha-D
      galactosyl oligosaccharides and produce lactic and acetic acids. They all were
      able to reduce stachyose and raffinose. Pentanal and n-hexanal were metabolized
      by Bifidobacterium breve MB233. These data indicate that bifidobacteria can be
      used for biotechnological processes that employ soymilk as the substrate. A
      product with low levels of alpha-D-galactosyl oligosaccharides and alkylic
      aldehydes may be obtained.

PMID- 9553800
TI  - A further review of the microbiological quality of bottled water sold in Canada:
      1992-1997 survey results.

PMID- 9553801
TI  - Amino acid decarboxylase capability of microorganisms isolated in Spanish
      fermented meat products.
AB  - Enterobacteria, lactic acid bacteria (LAB) and Gram-positive cocci were isolated
      from Spanish meat products. The most frequent species in the meat products
      studied were identified as Lactobacillus sake, Lactobacillus plantarum and
      Lactobacillus curvatus from De Man-Rogosa-Sharpe agar; Staphylococcus xylosus,
      Staphylococcus saprophyticus and Micrococcus varians from mannitol salt phenol
      red agar; and Hafnia alvei, Escherichia coli, Pseudomonas fluorescens,
      Enterobacter amnigenes and Enterobacter aerogenes from violet red bile dextrose
      agar. The amino acid decarboxylase activity of the microorganisms isolated was
      assayed. Enterobacteria had higher amino acid decarboxylase activity than the
      other groups. LAB did not show any significant amino acid decarboxylase
      capability in this study.

PMID- 9553802
TI  - Characterization of plasmids from Listeria monocytogenes and Listeria innocua
      strains isolated from short-ripened cheeses.
AB  - The plasmid content of 30 isolates of Listeria monocytogenes and 18 isolates of
      Listeria innocua obtained from short-ripened cheeses was analysed. The isolates
      of L. monocytogenes serogroup 1 harboured a single plasmid, pLM33 (33.2 kbp),
      whereas the serogroup 4 isolates did not contain plasmids. One group of L.
      innocua strains harboured the plasmid pLI71 (71 kbp) and another one contained
      two plasmids: pLI59 (59.5 kbp) and pLI56 (56.5 kbp). These plasmid groups were in
      accordance with clusters previously defined by pulsed-field gel electrophoresis
      analysis of the chromosomal DNA of Listeria isolates. Plasmids pLM33, pLI71 and
      pLI59 shared homology regions of at least 20 kbp. Plasmid pLI56 did not encode
      genes for any known character (such as carbohydrate fermentation, resistance to
      antibiotics, heavy metals or disinfectants, growth at low pH, NaCl tolerance or
      thermal inactivation by pasteurisation) and displayed different characteristics
      to the other three plasmids. It was also the only one cured from the parent
      strain and the sole plasmid not digested by the restriction enzyme PstI. In
      addition, its lack of homology with pLM33, pLI71 and pLI59 enhanced the
      possibility of a different origin for plasmid pLI56.

PMID- 9553803
TI  - Probiotics.

PMID- 9553804
TI  - The diagnostic utility of inhibin staining in ovarian neoplasms.
AB  - Previous immunohistologic studies have suggested that the antibody to the alpha
      subunit of inhibin is a sensitive marker of sex cord-stromal differentiation.
      However, detection has also been reported within both ovarian epithelial and germ
      cell tumors. To further study the normal tissue distribution of inhibin and the
      utility of its detection for the differential diagnosis of ovarian sex cord
      stromal neoplasms, normal tissues and 225 lesions including sex cord-stromal
      lesions, ovarian epithelial and stromal cancers, ovarian and testicular germ cell
      tumors, metastases to the ovary, and non-ovarian cancers were analyzed using semi
      automated immunohistochemistry. In normal tissues, immunostaining was found in
      cell subsets of the ovary, testis, adrenal gland, placenta, and kidney. All sex
      cord-stromal tumors were inhibin-positive and 37 of 50 (74%) cases exhibited at
      least moderate to strong immunostaining. Two cases originally diagnosed as adult
      granulosa cell tumors that were inhibin-negative were reassessed; diagnoses of
      endometrioid stromal sarcoma and endometrioid carcinoma with sertoliform features
      were rendered. In other primary or metastatic ovarian lesions or metastases to
      the ovary, weak to moderate immunostaining was found in only 4 of 84 (4.8%)
      cases, including ovarian clear cell carcinoma (2/2), uterine clear cell
      carcinomas metastatic to the ovary (1/3), and serous papillary carcinoma (1/2).
      Similarly, only 4 of 66 (6.1%) non-ovarian neoplasms exhibited weak
      immunostaining, including melanoma (1/5), uterine endometrioid carcinoma (1/2),
      transitional cell carcinoma (1/3), and breast adenocarcinoma (1/8). Only one case
      of a non-sex cord-stromal tumor had moderate or strong immunostaining. Based on
      these results, immunohistologic detection of the alpha subunit of inhibin is a
      useful adjunct in the differential diagnosis of sex cord-stromal neoplasms.

PMID- 9553805
TI  - Frequent loss of chromosome 12 in human epithelial ovarian tumors: a chromosomal
      in situ hybridization study.
AB  - The short arm isochromosome of chromosome 12 and trisomy 12 are well-established
      chromosomal alterations in human ovarian germ cell tumors. However, numerical
      aberrations of chromosome 12 in epithelial ovarian tumors (EOTs) are highly
      controversial; both trisomy 12 and monosomy 12 have been observed. We performed
      chromosomal in situ hybridization in paraffin-embedded and formalin-fixed tissue
      sections of 31 EOTs. Twenty-five EOTs could be evaluated statistically (2
      mucinous, 11 serous, 5 endometrioid, 3 borderline, and 4 other epithelial-type
      tumors) to examine the copy number of chromosome 12 and 15. The frequency
      distribution of hybridization signals with alpha-satellite centromeric DNA probes
      for chromosome 15 revealed disomy in all cases. However, we found the loss of
      chromosome 12 in 16 of 25 tumor samples. No correlation was found between the
      presence of monosomy 12 and the clinical stage of the tumors. Frequent loss of
      chromosome 12 may indicate that this chromosome is involved in the tumorigenesis
      of EOTs. Further studies are needed to clarify whether loss of chromosome 12 is
      an early or late event in ovarian carcinogenesis.

PMID- 9553806
TI  - Primary ovarian rhabdomyosarcoma: a report of 13 cases.
AB  - Primary ovarian rhabdomyosarcomas were found in 13 patients aged 7 to 79 (mean
      37) years who had reported abdominal pain and swelling. Six tumors involved the
      right ovary, 3 involved the left, 1 involved both, and the laterality was unknown
      in 3 cases. Four tumors were stage I, 2 were stage II, 4 were stage III, and 2
      were stage IV; the stage of 1 tumor is not known. The tumors ranged from 10 to
      19.5 (average 16) cm in diameter and had solid sectioned surfaces that varied
      from yellow to white to pink and from gelatinous to hemorrhagic. Microscopically,
      11 tumors were embryonal and 2 were alveolar rhabdomyosarcomas. Follow-up
      information, available for 11 patients, revealed that 7 died of disease 10 days
      to 26 months postoperatively; 2 of these patients had stage II disease, 3 had
      stage III, and 2 had stage IV. Four patients were alive 2 to 9 months
      postoperatively; 3 had stage I and 1 had stage III disease. These 13 tumors and
      an additional 10 from the English-language literature are reviewed and the
      differential diagnosis of ovarian rhabdomyosarcoma is discussed.

PMID- 9553807
TI  - Membranous fat necrosis in mature cystic teratomas of the ovary.
AB  - We identified and documented the occurrence of membranous fat necrosis (MFN) in
      217 mature cystic teratomas (MCTs) of the ovary. Cysts lined by an eosinophilic
      and scalloped membrane with pseudopapillary infoldings, the characteristic
      histologic features of MFN, were identified in 9 tumors. The membranes had the
      histochemical staining properties of ceroid, as evidenced by periodic acid
      Schiff, sudan black, and long Ziehl Neelsen (ZN) positivity, diastase resistance,
      and autofluorescence. The causes and pathogenesis of MFN are enigmatic, but
      trauma, torsion, and ischemia are probable factors. MFN is a distinct entity in
      ovarian MCTs and heightened awareness will increase its histopathologic
      recognition.

PMID- 9553808
TI  - Desmin expression in reactive mesothelium: a potential aid in evaluation of
      gynecologic specimens.
AB  - Desmin is a marker of smooth and striated muscle, but evidence is accumulating
      that it may be expressed by human mesothelium. The aim of this study was to
      describe desmin expression in normal, reactive, and hyperplastic peritoneal
      mesothelium, and to evaluate its potential use as a marker for differentiating
      between epithelial and mesothelial proliferations. We immunohistochemically
      studied 27 tissue specimens (from 22 patients) with reactive mesothelium,
      including omentum (n = 14), fallopian tubes (n = 7), ovaries (n = 3), ascitic
      fluid (n = 1), and peritoneal washings (n = 2). Ovarian surface epithelium (OSE)
      from 9 cases and 28 ovarian surface epithelial tumors was evaluated for
      comparison. The desmin expression pattern in the mesothelium, which was similar
      to but less consistent than that of cytokeratins, was evident in flat and
      reactive mesothelium, including hyperplastic mesothelial sheets and mesothelium
      entrapped in clefts. Mesothelial pseudoglandular structures, present in three
      cases, were predominantly negative for desmin. Desmin expression was observed in
      the OSE in 4 of 9 cases but not in any mullerian-derived epithelium or mullerian
      type tumor. Thus, in contrast to cytokeratins, desmin discriminated mesothelial
      cells from mullerian type epithelia. Compared with vimentin, desmin discriminated
      mesothelial cells from other tissues except muscle cells. We conclude that desmin
      may be used in addition to cytokeratins and vimentin as a marker of peritoneal
      mesothelium.

PMID- 9553809
TI  - Distinctive p53 and mdm2 immunohistochemical expression profiles suggest
      different pathogenetic pathways in poorly differentiated endometrial carcinoma.
AB  - Endometrial serous carcinoma (ESC) and FIGO (International Federation of
      Gynecology and Obstetrics) grade 3 endometrioid adenocarcinoma (EC) are high
      grade endometrial tumors that have different clinical and morphologic attributes.
      Alteration of p53 tumor suppressor protein function has been implicated in the
      pathogenesis of both tumors, although the mechanisms may differ. We sought to
      investigate this difference by comparing immunohistochemical expression of p53
      and mdm2. p53 immunoreactivity often correlates with gene mutation, whereas
      increased mdm2 expression is linked to complex formation with wild-type p53
      resulting in its inactivation. Twenty cases of ESC and 21 cases of EC were
      evaluated and an immunoreactivity score (IRS) was assigned using both the
      percentage of cells stained and the intensity of staining. The overall IRSs were
      significantly different in ESCs versus ECs for both p53 and mdm2 (p < 0.001 and p
      < 0.01, respectively). Strong mean immunoreactivity for p53 was detected in 15
      (75%) ESCs as compared to only weak mean immunoreactivity in 17 (81%) ECs.
      Conversely, for mdm2 expression, 17 (81%) ECs had moderate mean immunoreactivity
      whereas 9 (45%) ESCs showed only weak mean immunoreactivity. mdm2 expression more
      closely correlated with p53 expression in ECs than in ESCs. In ECs, mdm2 was
      detected in 16 of 17 (94%) p53-positive tumors but in only 1 of 3 (33%) p53
      negative tumors (p < 0.025). In ESCs, mdm2 was detected in 9 of 15 (60%) p53
      positive tumors but in none of the 5 p53-negative tumors (p < 0.10). Overall, our
      results demonstrate an inverse relationship between the expression of p53 and
      mdm2 in ESC versus high-grade EC. Specifically, strong p53 immunoreactivity is
      associated with weak mdm2 expression-in ESC and weak p53 expression is associated
      with moderate mdm2 expression in EC. These results suggest different pathogenetic
      pathways resulting in loss of normal p53 function in these two tumors: by p53
      gene mutation (strong p53 overexpression) in ESCs, or by mdm2 complex formation
      and inactivation of p53 in high-grade ECs.

PMID- 9553810
TI  - Random nuclear p53 overexpression pattern in tamoxifen-mediated endometrial
      carcinoma.
AB  - In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial
      carcinogenesis may not involve estrogenic pathways because of random estrogen
      receptor positivity among endometrial carcinomas with and without TAM treatment
      for breast cancer. DNA adduct formation (reported in rat liver and human
      endometrium) was considered to be a more plausible mechanism for TAM-mediated
      carcinogenesis. To examine the reported correlation between DNA adduct formation
      and p53, the present study examined p53 expression in the endometrial carcinomas
      reported in the previous study. Seven endometrial adenocarcinomas associated with
      long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM
      treatment but with history of breast carcinoma were immunohistochemically
      investigated for nuclear p53 expression. The bcl-2 product was also examined.
      Diffuse and intense nuclear reactivity for p53 protein was present in only one
      TAM-related case. Essentially, no differences were observed in the bcl-2 staining
      patterns of TAM-treated and -untreated patients with cancer. Thus, p53
      overexpression in endometrial carcinomas occurring in patients with breast cancer
      seems to be not specific for TAM-treated patients, and, if DNA adduct formation
      has any role in this type of endometrial carcinogenesis, it may not be related
      preferentially to p53 gene alteration. Further studies are needed to understand
      the precise mechanism(s) of the endometrial carcinogenesis.

PMID- 9553811
TI  - Morphologic and immunophenotypic characterization of foam cells in endometrial
      lesions.
AB  - The detection of foam cells in cervicovaginal smears obtained from postmenopausal
      women suggests the possibility of an endometrial lesion. Ultrastructural studies
      have suggested that foam cells represent endometrial stromal cells but the
      histogenesis of these cells has not been firmly established. To investigate the
      origin and diagnostic significance of foam cells, we analyzed the morphology and
      immunophenotype of these cells in endometrial tissue specimens and correlated the
      findings with cervical smears obtained within the preceding 6 months. Selected
      biopsies containing foam cells were evaluated using four well-characterized
      macrophage markers: KP-1(CD68), HAM 56, MAC 387, and lysozyme. Foam cells were
      found in 11 (38%) of 29 simple hyperplasias, 7 (50%) of 14 complex hyperplasias,
      6 (50%) of 12 complex atypical hyperplasias, 21 (70%) of 30 adenocarcinomas, 1
      (4%) of 25 samples with stromal breakdown, and 0 of 30 specimens showing normal
      cycling endometrium. Foam cells were also found in smears preceding the
      histologic diagnosis of 2 (13%) simple hyperplasias, 2 (25%) complex
      hyperplasias, 3 (43%) complex atypical hyperplasias, 5 (28%) adenocarcinomas, 5
      (28%) cases of stromal breakdown, and 0 of 8 normal tissue specimens examined.
      Foam cells were immunoreactive with at least 2 of the 3 macrophage-specific
      antibodies in all 21 biopsies studied. Our results suggest that foam cells
      phenotypically represent macrophages and not endometrial stromal cells. Foam
      cells are identified in a significant percentage of cervical smears and
      endometrial tissue specimens obtained from women with endometrial pathology. The
      morphology and immunophenotype of foam cells, however, does not appear to be
      useful in distinguishing benign endometrial stromal breakdown, endometrial
      hyperplasia, and endometrial adenocarcinoma.

PMID- 9553812
TI  - Disruption of the E1 and E2 reading frames of HPV 16 in cervical carcinoma is
      associated with poor prognosis.
AB  - The E1 and E2 reading frames of 158 cervical carcinoma samples containing human
      papillomavirus (HPV) 16 were mapped using polymerase chain reaction (PCR). The
      reading frames were amplified using primers spanning the entire genes. Of the
      analyzed samples, 23% showed no amplification with the E1 primers and 29% showed
      no amplification with the E2 primers. There was an overlap, but not complete
      identity, between the E1- and E2-disrupted groups. All E1- and E2-negative
      samples were further analyzed with primers spanning subsections of the E1 and E2
      reading frames, which together covered the entire genes. Of the 35 samples
      negative for E1, 11 were positive in specific amplification of the 3' end of the
      E1 gene. Several different subsections of E2 could be amplified from most samples
      negative for the entire gene (37/46). Five classes of patterns were found, in
      which either all subsections of the E2 gene or subsections in the 5', middle, or
      3' end were disrupted. Although a variable pattern of disruption/deletion in the
      E1-E2 area of the HPV 16 genome was found in cervical carcinoma, the 5' end
      disruption was the most common one in both E1 and E2. Patients with carcinomas
      showing disruptions in E1/E2 had a poorer survival than those without such
      changes, and E1 disruptions were the most important prognostically.

PMID- 9553813
TI  - Lectins in the vulva. I. Normal vulvar epithelium and epithelium adjacent to
      vulvar intraepithelial neoplasia and squamous cell carcinoma.
AB  - Lectins were used to investigate the cell surface oligosaccharide expression in
      normal vulvar epithelium from premenopausal and postmenopausal volunteer women.
      In addition, histologically normal epithelium adjacent to high-grade vulvar
      intraepithelial neoplasia (VIN III) and adjacent to vulvar tumors was examined
      with lectins for evidence of a possible "field change" surrounding these vulvar
      lesions. Seventeen vulvar biopsies were obtained prospectively from volunteer
      women, and 20 and 40 cases, respectively, of VIN III and vulvar squamous cell
      carcinoma were randomly chosen from pathology archives. Thirteen of the 20 VIN
      cases and all 40 vulvar carcinomas contained at least 2 cm of histologically
      normal-appearing epithelium adjacent to the vulvar lesion suitable for analysis.
      No alterations to lectin binding in normal vulvar epithelium with respect to
      patient age, menopausal status, phase of menstrual cycle, estrogen therapy, or
      history of cervical intraepithelial neoplasia were shown. ABO blood group antigen
      status affected epithelial binding for lectins HPA and UEAI (p < 0.005 and p <
      0.001, respectively). In addition, lectins SNA, MPA, and LCA identified markers
      of cellular differentiation and maturation. T-antigen expression (as shown by the
      lectin PNA) was almost universally present in histologically normal epithelium
      adjacent to VIN and vulvar tumors, contrasting with the lack of PNA binding in
      normal vulvar epithelium from volunteer women (p < 0.001 and p < 0.001), a
      finding suggestive of a local "field change" surrounding preinvasive and invasive
      vulvar lesions.

PMID- 9553814
TI  - Lectins in the vulva. II. Vulvar intraepithelial neoplasia and squamous cell
      carcinoma.
AB  - This study used lectins as histologic probes to determine the cell surface
      oligosaccharide expression in different grades and types of vulvar
      intraepithelial neoplasia (VIN). Lectin binding patterns in metastasizing and non
      metastasizing squamous cell carcinomas (SCCs) of the vulva were also compared to
      correlate lectin binding patterns with metastatic potential and other
      clinical/tumor characteristics. Twenty cases each of VIN epithelium,
      metastasizing SCC, and non-metastasizing vulvar carcinoma were randomly chosen
      from the pathology archives. Sixteen lectins were used to probe individual
      terminal oligosaccharide residues in formalin-fixed, paraffin-embedded tissue
      specimens from these cases through an indirect immunohistochemical technique.
      There were no differences in lectin binding patterns between the different
      histologic subtypes of VIN. In addition, there were no consistent differences
      between metastasizing and non-metastasizing primary tumors and no major
      differences in staining patterns between nodal metastases and the corresponding
      primary tumors. Furthermore, there was no identifiable correlation between lectin
      binding patterns and subsequent survival or local or regional recurrence;
      however, lectin staining of invasive tumor cells did appear to be related to
      local invasiveness. In addition, positive PNA binding was found to be a constant
      finding in each of the VIN and invasive SCC cases, confirming that the T-antigen
      becomes unmasked during the process of vulvar carcinogenesis. However, poorly
      differentiated areas consistently showed absent lectin binding, suggesting loss
      of specific glycosyl transferase activities. In addition, the blood group "A"
      antigen appears to be lost during the process of tumorgenesis, although the blood
      group "O" antigen appears to be preserved.

PMID- 9553815
TI  - Fibroadenoma phyllodes arising in vulvar supernumerary breast tissue: report of
      two cases.
AB  - Ectopic breast tissue, found along the mammary line or sometimes outside it, can
      exhibit pathologic changes similar to those of the eutopic mammary gland.
      Fibroadenoma phyllodes, an unusual variant of mammary phyllodes tumor with
      stromal cellularity similar to a conventional fibroadenoma, rarely arises outside
      of breast. Its histogenesis is unclear; although some cases suggest an origin in
      cutaneous adnexa, the presence of normal breast tissue surrounding other tumors
      favors an ectopic mammary origin. Two cases of fibroadenoma phyllodes arising in
      ectopic vulvar breast tissue are described.

PMID- 9553816
TI  - Sarcomatoid squamous cell carcinoma of the uterine cervix with osteoclast-like
      giant cells: report of two cases.
AB  - Two postmenopausal women with sarcomatoid squamous cell carcinoma (SSCC) of the
      uterine cervix are described. This report brings the total number of reported
      SSCCs in the lower female genital tract to 11. The gross and microscopic features
      of our SSCCs were similar to those of SSCCs in the digestive and upper
      respiratory tracts with the additional finding of osteoclast-like giant cells in
      each case. The behaviour and differential diagnosis of these tumors are briefly
      discussed.

PMID- 9553817
TI  - Leiomyomatosis peritonealis disseminata, endometriosis, and multicystic
      mesothelioma: an unusual association.
AB  - A 32-year-old, previously healthy woman with a diffuse, complex tumoral process
      is described. While she was being evaluated for primary infertility, a
      laparoscopic procedure revealed a disseminated peritoneal process associated with
      bilateral ovarian lesions. A clinical diagnosis of stage III ovarian cancer was
      made and total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy
      were performed. Pathologic studies showed an admixture of leiomyomatosis
      peritonealis disseminata (LPD) endometriosis, and an extensive multicystic
      mesothelial proliferation. Although endometriosis is known to occur in
      conjunction with either LPD or multicystic mesothelioma, to our knowledge this is
      the first report of all three lesions occurring simultaneously.

PMID- 9553818
TI  - Dr. Arthur T. Hertig.

PMID- 9553819
TI  - Gynandroblastoma with elements of juvenile granulosa cell tumor.

PMID- 9553820
TI  - Connecting to Internet.

PMID- 9553821
TI  - Advancing nursing ethics: time to set a new global agenda?

PMID- 9553822
TI  - Marketing and nursing in a competitive environment.
AB  - Marketing can no longer be considered vulgar commercialism. Ethically applied,
      marketing is in fact one of the necessary building stones and development tools
      for the future development of nursing. In the new competitive environment being
      created in health sectors to improve efficiency and cost-effectiveness, the
      nursing profession must learn to use marketing techniques to survey the needs,
      identify gaps in services and develop products and services that will be relevant
      for today's empowered consumer.

PMID- 9553823
TI  - Sharing in practice: new partnerships for health.
AB  - A vital part of health care, sharing in practice is not a vision for the future
      but the reality of today. Below, the meaning and implications of sharing in
      practice not just for nursing but for health care.

PMID- 9553824
TI  - International partnerships in nursing education.
AB  - As economies are shrinking, international partnerships in nursing education are
      growing, with the more established educational institutions launching not only on
      site internationally focused programmes but also educational partnerships that
      cross borders, regions, societies, cultures, languages and educational and
      nursing traditions. Below, some issues related to initiating and maintaining
      partnerships, as well as the benefits and problems based on personal experience
      with these partnerships in developing countries.

PMID- 9553826
TI  - Nursing and home care in Europe.
AB  - The demographic trend of a rapidly ageing society becomes increasingly
      persuasive. More chronically ill patients will be discharged to home care. More
      people with psychotic problems and debilitating diseases will be living in
      communities. All require nursing care. This situation is recognized everywhere
      and no boundaries can change this future.

PMID- 9553825
TI  - An action approach to redesigning a patient-centred unit.
AB  - Receptiveness to innovation is critical in orchestrating change and learning to
      use new technology in a redesigned work environment. The patient-centred unit
      redesign approach (PCURA) provides a guide for unit assessment in many healthcare
      settings. The backbone of the PCURA approach: work excitement and unit culture
      assessment.

PMID- 9553827
TI  - The truth and nothing but the truth: objectivity in alternative and orthodox
      biomedicine?

PMID- 9553828
TI  - Topical progesterone cream application and overdosing.

PMID- 9553829
TI  - Tobacco as a psychiatric remedy.

PMID- 9553830
TI  - Misuse of herbal remedies: the case of an outbreak of terminal renal failure in
      Belgium (Chinese herbs nephropathy)
AB  - At least 100 cases of extensive interstitial fibrosis of the kidneys were
      observed in Belgium in women who had followed a weight-loss regimen that included
      the use of Chinese herbs. The possible relation between the renal disease and
      these Chinese herbs was investigated. It was shown that the prescribed Chinese
      herb called Stephania tetrandra was, in fact, inadvertently replaced by another
      Chinese herb, namely Aristolochia fangchi in the powdered extracts delivered in
      Belgium and in France. The development of renal disease in about 100 patients
      exposed to the so-called Stephania tetrandra stresses the need for more stringent
      control of herbal medicine.

PMID- 9553831
TI  - Chinese herbs: risk, side effects, and poisoning: the case for objective
      reporting and analysis reveals serious misrepresentation.

PMID- 9553832
TI  - Chinese medicine users in the United States. Part I: Utilization, satisfaction,
      medical plurality.
AB  - OBJECTIVES: Chinese medicine is growing in popularity and offers an important
      alternative or complement to biomedical care, but little is known of who uses it
      or why they purchase it. This article reports the first in-depth, large-scale (n
      = 575) survey of United States acupuncture users. DESIGN: An anonymous mixed
      quantitative-qualitative survey questionnaire assessed user demographics, Chinese
      medicine modalities used, complaints, response to care, other health-care used,
      and satisfaction with care in six general-service clinics in five states. RESULTS
      AND CONCLUSIONS: The user demographic picture was of mid-age, well-educated,
      employed, mid-income patients. They sought care for a wide variety of conditions;
      top uses were for relief of musculoskeletal dysfunction, mood care, and wellness
      care. A large majority reported "disappearance" or "improvement" of symptoms,
      improved quality of life, and reduced use of selected measures including
      prescription drugs and surgery. Respondents reported utilizing a wide array of
      practices in addition to Chinese medicine, while also expressing extremely high
      satisfaction with Chinese medicine care. The evidence indicates that these
      respondents behave as astute consumers within a plural health care system. Part
      II (in press) details reasons given for satisfaction and situates respondent
      attitudes within a larger sociocultural framework.

PMID- 9553833
TI  - Effect of acupuncture stimulation of the auricular sympathetic point on evoked
      sudomotor response.
AB  - OBJECTIVES: To investigate whether stimulation of the auricular sympathetic
      acupuncture point would affect the mean maximum amplitude of evoked sudomotor
      responses. DESIGN: A placebo-controlled trial. Two types of controls were used:
      no acupuncture and acupuncture of an alternate "non-sympathetic nervous system"
      related (i.e., a non-sympathetic, placebo) point. Subjects were included in
      either the placebo or the test group. Each subject would have one session of
      acupuncture and one session without acupuncture, the acupuncture was applied in
      either the first or the second session. Initially, each group was unaware in
      which of the two sessions they would receive acupuncture (cross-over design).
      Each individual was unaware of which group they were to participate in.
      SETTINGS/LOCATION: A quiet, sealed room with a constant temperature, in the
      research department of the Anglo-European College of Chiropractic. SUBJECTS:
      Thirty-eight asymptomatic male, white volunteers (18 to 40 years old).
      INTERVENTIONS: The two groups underwent two electrodermal response (EDR)
      recording sessions, at an interval of 5 weeks. During each session, they were
      also presented with eight stimuli, each of which was designed to stimulate the
      sympathetic nervous system. In each session, subjects either received auricular
      acupuncture (AA) or did not. OUTCOME MEASURES: The maximum amplitude of the EDR
      for each stimulus. RESULTS: AA at the non-sympathetic, placebo point
      significantly increased EDR both with respect to the individual stimuli (p < or =
      0.05 to < or = 0.001) and for the pooled data (p = 0.0001). AA to the sympathetic
      point produced no significant change in EDR for either individual stimuli (p
      range > or = 0.8 to > or = 0.1) or for the pooled data (p > 0.8). A significant
      difference was found between the results from placebo and sympathetic point
      stimulated groups during AA for 2 of the 8 stimuli (p < 0.05), and for the pooled
      data from all 8 stimuli (p = 0.0006). CONCLUSION: Stimulation of the sympathetic
      AA point significantly decreased the stimulus-evoked EDR when compared with an AA
      stimulation to a non-sympathetic (placebo) point. However, it did not
      significantly alter EDR compared with no treatment. This implies that the
      increase in response as a result of inserting the needles was negated by placing
      the electrodes in the AA sympathetic point. Consequently, one might surmise that
      there may be a specific action of AA in respect to hyperhidrosis resulting from
      an increase in sympathetic activity.

PMID- 9553834
TI  - Extraction, assay, and analysis of antimicrobials from plants with activity
      against dental pathogens (Streptococcus sp.)
AB  - Many dental and periodontal diseases are largely a question of bacterial
      etiology. Dental caries develop due to an increase of strongly acidogenic and
      aciduric gram-positive bacteria while common forms of periodontal disease are
      linked to anaerobic gram-negative bacteria in subgingival plaque. Many plants and
      plant-derived antimicrobial components are used in folklore therapeutics for the
      treatment of periodontal disorders and for the purposes of oral hygiene. Some
      have been evaluated for possible use in modern medicine, while thousands of other
      potentially useful/plants have not been tested. In this study, we evaluated the
      feasibility of screening for antibacterials isolated from plants with activity
      against three representatives of oral streptococci. We developed and tested the
      following methodologies: (1) Extraction of antibacterial components from plants;
      (2) Assays for antibacterial activity; (3) Chromatographic methods for initial
      analysis of compounds of interest. The screening process for plant antimicrobials
      consisted of extraction of plant material and assay of antibacterial activity
      using a spotting test with the selected oral streptococci as indicator strains.
      In addition, we developed chromatographic procedures that allow characterization
      and optimization of initial isolation steps. Depending on the indicator
      microorganisms used, the screening assay can target additional pathogens
      including other streptococci (group A and B, and pneumococci) and periodontal
      pathogens such as Porphyromonas. Also, we noted that the activity of some
      extracts varied against different oral bacteria. Our conclusion, supported by
      extensive data, was that the screening for antimicrobials from plants is a
      feasible approach to the identification of natural compounds with antimicrobial
      properties against dental pathogens.

PMID- 9553835
TI  - The problem of treating dental pathogens.

PMID- 9553836
TI  - Can biological activity be maintained at ultra-high dilution? An overview of
      homeopathy, evidence, and Bayesian philosophy.
AB  - Forty percent of general practitioners in the Netherlands practice homeopathy.
      With over 100 homeopathic medical schools, homeopathy is practiced in India along
      with conventional Western medicine in government clinics. In Britain, 42% of
      general practitioners refer patients to homeopaths. Two recent meta-analyses of
      homeopathy both indicate that there is enough evidence to show that homeopathy
      has added effects over placebo. Against this evidence is a backdrop of
      considerable scientific scepticism. Homeopathic remedies are diluted substances-
      some are so diluted that statistically there are no molecules present to explain
      their proposed biological effects (ultra-high dilutions or UHDs). Without
      knowledge of the evidence, most scientists would reject UHD effects because of
      their intrinsic implausibility in the light of our current scientific
      understanding. The objective of this article is to critically review the major
      pieces of evidence on UHD effects and suggest how the scientific community should
      respond to its challenge. Such evidence has been conducted on a diverse range of
      assays--immunologic, physiological, behavioral, biochemical, and clinical in the
      form of trials of homeopathic remedies. Evidence of UHD effects has attracted the
      attention of physicists who have speculated on their physical mechanisms.
      Included is a critique of several experiments that form the Benveniste affair
      which was sparked by a publication in Nature that advocated the existence of UHD
      effects of anti-immunoglobulin E (IgE) on human basophils, and is the paradigm
      example of how a controversial phenomenon can split the scientific community. It
      is argued that if the phenomenon was uncontroversial, the evidence suffices to
      show that UHD effects exist. However, given that the observations contradict well
      established theory, normal science has to be abandoned and scientists need to
      decide for themselves what the likelihood of UHD effects are. Bayesian analysis
      describes how scientists ought rationally to change their prior beliefs in the
      light of evidence. Theories by Kuhn and Lakatos indicate that whether UHD effects
      are proved or not depends on the beliefs and behaviors of scientists in their
      communities. This article argues that there is as yet insufficient evidence to
      drive rational scientists to a consensus over UHD effects, even if they possessed
      knowledge of all the evidence. The difficulty in publishing high-quality UHD
      research in conventional journals prevents a fair assessment of UHD effects.
      Given that the existence of UHD effects would revolutionize science and medicine,
      and given the considerable empirical evidence of them, the philosophies of
      science tell us that possible UHD effects warrant serious investigation by
      conventional scientists and serious attention by scientific journals.

PMID- 9553837
TI  - Chemical sensitivity after intoxication at work with solvents: response to sauna
      therapy.
AB  - OBJECTIVES: The purpose of this case study is twofold. One, to illustrate a
      simple method of detoxification using heat chamber depuration (sauna). Second, to
      raise awareness in the practice of medicine of the importance of taking an
      environmentally oriented history. SUBJECT: A patient with a chronic, debilitating
      multisystem disorder of 20-years' duration related to a chemical sensitivity
      resulting from low-level exposure to toxic chemicals (solvents) at work.
      INTERVENTIONS: Detoxification treatment consisted of heat chamber depuration
      (sauna) together with a specific protocol of oral and intravenous therapy.
      Appropriate advice was offered related to choosing a safe and suitable workplace.
      OUTCOME MEASURES: Observation of the dynamic interaction and elimination of
      chlorinated and aromatic hydrocarbons (solvents) from the patient's bloodstream
      and related clinical improvement during the course of treatment. RESULTS: The
      patient was able to discontinue, without ill effect, all medications previously
      prescribed to treat her symptoms. Heat chamber depuration (sauna) detoxification
      treatment brought substantial release of symptoms and returned the individual to
      gainful employment. CONCLUSION: The connection between symptoms of chronic
      degenerative diseases and environmental and/or nutritional factors is missed in
      many cases due to lack of obtaining an environmentally oriented medical history.
      Taking such a history and dealing with the cause of illness using avoidance
      and/or appropriate therapy is preventive and cost-effective for both the patient
      and society.

PMID- 9553838
TI  - Some biological actions of alkylglycerols from shark liver oil.
AB  - Shark liver oil has been used for over 40 years as both a therapeutic and
      preventive agent. The active ingredients in shark liver oil have been found to be
      a group of ether-linked glycerols known as alkylglycerols. Initial clinical use
      was for treating leukemias, and later to prevent radiation sickness from cancer x
      ray therapy. Studies over the last 30 years have shown that alkylglycerols are
      multifunctional. The level of natural alkylglycerols rises within tumor cells,
      apparently in an effort to control cell growth. Recent studies indicate that the
      activation of protein kinase C, an essential step in cell proliferation, can be
      inhibited by alkylglycerols. This action suggests a competitive inhibition of 1.2
      diacylglycerol by alkylglycerols. Further studies on the immunostimulatory action
      of alkylglycerols suggest a primary action on the macrophage. The process of
      macrophage activation has been demonstrated with both synthetic and natural
      alkylglycerols. While the exact mechanism has not been found, both an autocrine
      and paracrine system have been suggested. Shark liver is a major natural source
      of alkylglycerols, which have no known side effects in dosages of 100 mg three
      times a day. The information presented in this article suggests that
      alkylglycerols may be used both as an adjunct therapy in the treatment of
      neoplastic disorders and as an immune booster in infectious diseases.

PMID- 9553839
TI  - Soul consciousness and human suffering: psychotherapeutic approaches to healing.
AB  - A clinical approach to the understanding of disturbances of the psyche that
      otherwise would be regarded as pathological states of mind is described. A
      parallel is drawn between psychoanalytic object relations theory and "spiritual
      object relations," working from the premise that mind comes before matter. A
      number of clinical examples illustrate how both psychological and spiritual
      interpretations may be applied and that highlight the need for psychiatrists to
      be open to the transpersonal frame of reference.

PMID- 9553840
TI  - Clinical management of brain metastasis.
AB  - Brain metastasis is a common complication occurring in about 15-20% of all cancer
      patients. For the initial management, distinguishing between three types of
      presentation is essential: de novo brain metastasis, simultaneous presentation of
      both brain metastasis and the primary tumour (usually lung carcinoma), and the
      presentation of a patient known to have systemic cancer developing a brain
      metastasis. For de novo brain metastasis, surgery is required, and detecting the
      primary tumour is of limited value. For simultaneous presentation, both a
      craniotomy and a thoracotomy may be indicated and may lead to cure in a number of
      cases. For a sequential presentation, the outcome is determined by a number of
      independent prognostic factors: age, performance status, and the extent of
      metastatic disease. In relatively young patients with a single brain metastasis,
      good performance status and no progression of systemic disease, treatment by
      either surgery or radiosurgery in combination with whole brain radiation therapy
      is indicated. Otherwise, as in multiple brain metastases, radiation therapy only
      is the main treatment. For symptomatic therapy of brain oedema or increased
      intracranial pressure, dexamethasone is administered. The standard doses of
      dexamethasone may vary between 4 and 16 mg/day, depending on the severity of
      symptoms.

PMID- 9553841
TI  - Serum antibodies against membranous labyrinth in patients with "idiopathic"
      bilateral vestibulopathy.
AB  - To investigate the possibility of an autoimmune mechanism in idiopathic bilateral
      vestibulopathy (IBV), we screened patients' sera for antibodies against inner ear
      structures. IgG antibodies against membranous labyrinth (ampulla, semicircular
      canals, saccule and utricle) were detected in 8 of 12 patients by
      immunofluorescence on rat inner ear cryosections. All but one serum of 22 healthy
      controls and the sera of 6 patients with known autoimmune disorders showed only
      background staining. Low-titre anti-nuclear IgM antibodies were present in three
      control sera and one IBV serum. High-titre anti-nuclear IgM was found in a
      patient with lupus erythematosus and in one with scleroderma. Anti-nuclear IgM
      was not organ-specific. No human serum used contained detectable anti-vascular
      preformed antibodies. Cross-reactivity to sections of liver, kidney, cornea,
      brain and skeletal muscle was absent. Double-staining for IgG and F-actin, the
      primary constituent of hair cell cilia, did not show predominant Ig-coating of
      sensory hair cells. Immunosuppressive therapy in 3 IBV patients did not improve
      the disorder, probably owing to irreversible loss of sensory and neural
      structures. These data suggest that the bulk of anti-labyrinthine autoantibodies
      may be an epiphenomenon, yet a small subgroup of organ-specific autoantibodies
      may synergize with a cellular response in the development of vestibular lesions.

PMID- 9553843
TI  - Effect of transcutaneous electrical nerve stimulation (TENS) on central nervous
      system amplification of somatosensory input.
AB  - The effect of transcutaneous electrical nerve stimulation (TENS) on the central
      nervous system amplification process was investigated focusing on the dorsal
      column-medial lemniscal pathway, because the dorsal column nucleus was recently
      shown to receive multiple sources of sensory information, including pain. Short
      latency somatosensory evoked potentials (SSEPs) were recorded in ten healthy
      normal volunteers. Amplitude changes in each SSEP component (the N9 brachial
      plexus potential, the P14 potential that originates from the cervicomedullary
      junction, spinal N13/P13 generated by the cervical dorsal horn and the cortical
      N20/P25 potential) were studied at stimulus strengths ranging from the threshold
      (40% maximum stimulus) to 2.5 times the threshold (maximum). The findings suggest
      that sensory amplification begins at the P14 generator source near the cuneate
      nucleus. There was no statistically significant difference in sensory
      amplification between P14 and cortical N20/P25, indicating that the cuneate
      nucleus is the main site of the central amplifying process. When TENS was applied
      to the palm distal to the median nerve stimulation used for SSEP, cortical
      N20/P25 amplification disappeared, evidence that TENS suppresses the central
      amplification phenomenon, most probably at the level of the cuneate nucleus.

PMID- 9553842
TI  - Pulsatile tinnitus--a review of 84 patients.
AB  - Pulsatile tinnitus can be annoying for a patient and can also be the only clue to
      a potentially devastating and life-threatening disease. In order to understand
      its clinical spectrum and management better we analysed the files of 84 patients
      seen at our institution over a 10-year period. Noninvasive techniques
      (ultrasound, computed tomography, magnetic resonance imaging) and angiography
      were employed as investigations tailored to the individual patient. A vascular
      disorder [i.e. arteriovenous fistula, dissection of the internal carotid artery
      (ICA), fibromuscular dysplasia, aneurysm of the ICA and sinus thrombosis] was
      found in 36 patients (42%), most commonly a dural arteriovenous fistula or a
      carotid-cavernous sinus fistula. In 26 patients with a vascular abnormality,
      pulsatile tinnitus was the presenting symptom. In 12 patients (14%), nonvascular
      disorders such as glomus tumour or intracranial hypertension with a variety of
      causes explained the tinnitus. We conclude that patients with pulsatile tinnitus
      should be investigated with noninvasive techniques. If these are negative or to
      clarify abnormal findings of noninvasive techniques selective angiography is
      needed for diagnosis and to guide treatment.

PMID- 9553844
TI  - Increased rate of factor V Leiden mutation in patients with cerebral venous
      thrombosis.
AB  - We investigated the association between cerebral venous thrombosis and hereditary
      resistance to activated protein C (APC) in 12 consecutive German patients with
      non-fatal cerebral venous thrombosis and in 187 controls without a history of
      thrombotic disorder. Three patients (25%) had a mutation in the factor V Leiden
      gene against only one subject in the control group. This difference was
      significant (P < 0.05), with an odds ratio of 11.7 (1.5-87; 95% confidence
      interval). Two patients carrying the mutation had additional common risk factors
      for thrombosis, and 2 had a positive family history of thromboembolism. We
      conclude that inherited APC resistance by a mutation in factor V Leiden is an
      important risk factor in non-fatal cerebral venous thrombosis. We recommend
      testing for APC resistance and, if abnormal for factor V Leiden mutation in
      patients with cerebral venous thrombosis.

PMID- 9553845
TI  - Functional correlates of callosal atrophy in relapsing-remitting multiple
      sclerosis patients. A preliminary MRI study.
AB  - In multiple sclerosis (MS), periventricular lesions produce atrophy of the corpus
      callosum (CC), as evidenced by magnetic resonance imaging (MRI). We investigated
      whether CC atrophy in relapsing-remitting MS patients is related to functional
      deficits. We compared 14 mildly disabled (mean Expanded Disability Status Scale
      score 2.7) relapsing-remitting MS patients with 14 age- und sex-matched controls.
      CC size was determined using sagittal T1-weighted MRI. The function of the CC was
      studied using a neuropsychological battery and neurophysiological evaluation
      based on visual stimulation using a divided visual field paradigm. The total area
      of the CC in patients (mean 5.3 cm2) was significantly (P = 0.002) smaller than
      in controls (mean 6.6 cm2). Patients showed left ear extinction using the
      dichotic listening test and impaired name learning, which was correlated with
      atrophy of the splenium. There were no differences in interhemispheric transfer
      time between patients and controls. Marked atrophy of the CC can be encountered
      in relapsing-remitting MS patients. The associated cerebral disconnection
      correlated with atrophy of expected regions of the CC, thus supporting
      topographical organization.

PMID- 9553846
TI  - Epineurial microvasculitis in proximal diabetic neuropathy.
AB  - Amongst the focal and multifocal neuropathies that are associated with diabetes
      mellitus one of the most common is a proximal predominantly motor lower limb
      neuropathy. Recent evidence has indicated that, at least in a proportion of
      cases, this may have an inflammatory basis. We have examined a consecutive series
      of 15 cases of proximal diabetic neuropathy (diabetic amyotrophy). These were
      characterized by proximal pain and asymmetric proximal or generalized lower limb
      muscle weakness, associated in some cases with radicular sensory involvement. Two
      thirds of the patients had an accompanying distal symmetric sensory
      polyneuropathy. Biopsy of the intermediate cutaneous nerve of the thigh, a
      sensory branch of the femoral nerve, showed epineurial microvasculitis in 3
      patients and nonvasculitic epineurial inflammatory infiltrates in another case.
      In a further case, microvasculitis was found in both in the sural nerve and a
      quadriceps muscle biopsy specimen. The detection of inflammatory changes appeared
      to be correlated with the occurrence of sensory radicular involvement. Whether
      similar changes are present in muscle nerves in this predominantly motor syndrome
      requires further study. Nevertheless, the present observations confirm the view
      that secondary vasculitic or other inflammatory reactions may contribute to some
      forms of diabetic neuropathy.

PMID- 9553847
TI  - Determinants of onset age in Friedreich's ataxia.
AB  - We studied the factors that might influence onset age in Friedreich's ataxia in
      41 cases (20 male, 21 female) homozygous for GAA expansion on the first intron of
      X25 gene. Patients came from 18 multiplex families (13 couples, 5 triplets). Mean
      age (SD) was 18.1 (8.9) years and did not differ by gender. Onset age and the
      sizes of the smaller (GAA1) and the larger (GAA2) allele in each pair showed high
      intrafamily correlation. We found an inverse correlation between age at onset and
      GAA1 size, but not between age at onset and GAA2 size. Stepwise multiple
      regression of onset age on GAA1 size, sibling onset age, and GAA2 size showed
      that GAA1 accounts for 73% of onset age variance, and sibling onset age for an
      additional 13%. The study demonstrates that, in addition to GAA expansion size,
      other environmental or genetic familial factors influence disease expression.

PMID- 9553848
TI  - Humoral immune response to p53 in malignant glioma.
AB  - p53 immunoreactivity and humoral immune response to p53 were examined in 14
      patients with malignant glioma, including 4 patients with leptomeningeal glioma
      cell dissemination. Twelve patients expressed p53 protein within the tumour
      tissue. p53 antibodies were detected in the serum in 2 of 14 patients but never
      in the cerebrospinal fluid (CSF). Soluble p53 protein was detected neither in
      serum nor in CSF of the glioma patients. CSF levels of the immunosuppressive
      cytokine, transforming growth factor (TGF)-beta, were elevated in the glioma
      patients, including those with a humoral response to p53. These preliminary
      findings raise the possibility of systemic humoral immune responses to antigens,
      including mutant p53, expressed by glioma cells in the central nervous system.

PMID- 9553849
TI  - Disorders of micturition in neurological patients. A clinical study of 786
      patients.
AB  - Our aim was to evaluate the utility and effectiveness of a study protocol for
      neurological involvement in neurological disorders. We studied a sample of 786
      patients with neurological disorders followed by the Neurological Department of
      Catania University and applied to them a four-step diagnostic protocol. Fifty-six
      per cent of the sample showed urological functional abnormalities; only 78
      patients (9.9%) presented with an organic urological disease. Among the
      vesicosphincteric dysfunctions, bladder hyperreflexia was the most common pattern
      with remarkable differences between diseases. The present study demonstrated the
      utility of a standardized urological protocol in the screening and detection of
      neurological involvement in neurological diseases. Our protocol showed good
      specificity and reasonable low costs.

PMID- 9553850
TI  - Diagnosis and treatment of intramedullary spinal cord sarcoidosis.

PMID- 9553851
TI  - Hemiparkinsonism-hemiatrophy: a new observation.

PMID- 9553852
TI  - Neuromyotonia, systemic lupus erythematosus and acetylcholine-receptor
      antibodies.

PMID- 9553853
TI  - Long-term functional prognosis of posterior injuries in high-energy pelvic
      disruption.
AB  - OBJECTIVE: This study sought to identify the long-term functional results of
      various posterior pelvic lesions and to determine whether such injuries benefit
      from exact reduction. DESIGN: Consecutive cohort of patients admitted for pelvic
      disruption between 1980 and 1990. SETTING: University hospital. PATIENTS: Eighty
      eight pelvic fractures in eighty-eight patients were classified according to the
      instability and anatomy of the posterior injury. Simple fractures of the pubic
      rami, minimally displaced fractures with pubic diastasis of less than 2.5
      centimeters, and fractures without other pelvic lesions (type B1 lesions, stage 1
      in the Tile classification) were all excluded. Patients with sequelae of
      associated lesions that could render functional evaluation difficult were also
      excluded. INTERVENTIONS: The initial status of the patient and the type of
      fracture determined the treatment. In the anteroposterior compression injuries
      group, an external fixator using the double-frame Hoffmann device was applied in
      twenty-eight cases to reduce a large external horizontal displacement, either
      immediately to control bleeding or later as definitive treatment when anterior
      internal fixation was not possible. Anterior internal fixation with a plate was
      used six times to repair a symphyseal disruption. In vertical shear injuries,
      tibial skeletal traction was used for six weeks as an attempt to stabilize
      vertical instability. In ten patients, traction alone was used. In other cases,
      traction was used in conjunction with an external fixator or internal pubic
      fixation. In impacted lateral compression injuries, simple bed rest for six weeks
      was used in cases of stable lesions. Skeletal traction was applied in ten
      patients of this group because of a potential vertical instability, particularly
      in cases with a comminuted sacral lesion. MAIN OUTCOME MEASURES: Anatomic
      diagnosis and evaluation of the reduction were made using anteroposterior, inlet,
      and outlet radiographs of the pelvic ring. To assess reduction, vertical,
      anteroposterior, and rotatory displacement was measured. Functional results were
      qualified based on the injury pattern and the quality of the final reduction and
      were then quantified according to the grading proposed by Majeed. RESULTS:
      Functional results varied according to injury anatomy, with fractures of the
      iliac wing and sacroiliac (SI) fracture-dislocations having the best prognosis.
      The quality of reduction did not affect the functional results. Conservative
      methods such as skeletal traction and external fixation generally gave
      satisfactory functional results. Conversely, however, pure SI lesions were
      associated with poor functional results, especially if reduction was not exact.
      CONCLUSIONS: This study shows that when the posterior injury is a fracture of the
      iliac wing or a mixed fracture with SI propagation, a long-term satisfactory
      functional result can be obtained without an exact reduction even in cases of
      vertical instability. Simple methods are usually sufficient, and it seems
      unnecessary to propose more aggressive treatment. It is important, however, to
      recognize that SI fracture-dislocations (17 percent in this series) seem to be
      quite different from pure SI disruptions in terms of persistent pain. Moreover,
      it appears that exact reduction of pure SI lesions is critical for good
      functional results, something that is difficult to obtain with conservative
      procedures. Sacral fractures represent a special problem for the surgeon because
      of the frequency of fair results in which neurologic lesions whose
      pathophysiology is poorly known seem to be responsible.

PMID- 9553854
TI  - Biomechanical evaluation of a low anterior wall fracture: correlation with the CT
      subchondral arc.
AB  - OBJECTIVE: To measure the effect of a simulated low anterior wall fracture of the
      acetabulum on load transmission in the hip joint. DESIGN: We measured the contact
      areas and pressure between the acetabulum and the femoral head of cadaveric
      pelves in three different conditions: intact, with an operatively created
      fracture of the anterior wall, and after anatomic reduction and internal fixation
      of the fracture. SETTING: Hips were loaded in simulated single-limb stance.
      Pressure and area measurements were made with Fuji pressure-sensitive film.
      SPECIMENS: Seven hip joints in seven whole pelves were tested. INTERVENTION:
      Anterior wall fractures were anatomically reduced and fixed. MAIN OUTCOME
      MEASUREMENTS: Contact area, load, and mean and maximum pressures were measured.
      RESULTS: Anterior wall fractures in our specimens entered the hip joint an
      average of 9.7 millimeters from the vertex of the acetabulum, corresponding to a
      45-degree roof arc measurement. Peripheral loading seen in the intact acetabulum
      was disrupted after fracture. The loading pattern was not restored to preinjury
      levels with anatomic reduction and fixation. There was no significant change in
      the contact area (p = 0.43), force (p = 0.06), or mean (p = 0.57) or maximum (p =
      0.20) pressures in the superior aspect of the acetabulum after creation of the
      anterior wall fracture. CONCLUSIONS: These results differ from those of previous
      studies with posterior wall acetabulum fractures, where significant increases in
      force and mean and maximum pressures were noted in the superior acetabulum after
      fracture. The lack of significant increases in superior acetabular pressures is
      discussed in relation to the mean computed tomographic subchondral arc of
      approximately ten millimeters in our specimens.

PMID- 9553855
TI  - Functional outcome of acromioclavicular joint injury in polytrauma patients.
AB  - OBJECTIVE: To evaluate the functional outcome of displaced acromioclavicular (AC)
      injuries in polytrauma patients. DESIGN: A matched, case-control study using a
      prospectively gathered trauma database. METHODS: Twelve polytrauma patients with
      a concomitant displaced acromioclavicular joint injury were matched to polytrauma
      patients without an acromioclavicular joint injury and to patients with an
      isolated displaced acromioclavicular joint injury. They were evaluated with a
      series of five shoulder questionnaires and the SF-36 general health status
      questionnaire. RESULTS: Shoulder function in polytrauma/acromioclavicular joint
      injured patients was consistently worse than in control patients with an isolated
      acromioclavicular joint injury. In addition, the presence of an acromioclavicular
      joint injury in a polytrauma patient had a negative effect on several components
      of the SF-36. CONCLUSIONS: A displaced acromioclavicular joint injury in a
      polytrauma patient has a greater effect on shoulder function than isolated
      acromioclavicular joint injuries when evaluated by both disease-specific and
      general health outcomes. Standard treatment methods may be inadequate for this
      group of patients.

PMID- 9553858
TI  - Mechanical characteristics of eight femoral intramedullary nailing systems.
AB  - OBJECTIVE: There are few nonproprietary papers addressing the mechanical strength
      of intramedullary nails; none address the characteristics of the proximal and
      distal ends of these devices. Our objective was to provide such data. DESIGN:
      Independent testing of eight femoral intramedullary nail systems at the proximal,
      middle, and distal regions was undertaken to evaluate strength and flexural
      rigidity (stiffness). METHODS: Each device, usually a reconstruction nail, was
      forty-two to forty-six centimeters in length. Four or five nails of each
      available size (range 9 to 13 millimeters in diameter) were tested for each
      system. The nails were cut into proximal, middle, and distal thirds. Each nail
      section was loaded to failure using a four-point bend test on a custom fixture
      (modification of the American Society of Testing Materials standard test).
      RESULTS: Significant variations (p < 0.05) were found in strength and stiffness
      between the middle and the proximal or distal aspects of some rods. A significant
      difference (p < 0.05) was observed when comparing the properties of earlier
      designs with the properties of more recent designs. Newer rod designs all
      performed in a similar manner with regard to strength. Strength and rigidity
      increased with increasing rod diameter in some but not all systems. CONCLUSIONS:
      Although none of the newer designs appeared to have superior static strength, the
      individual systems had significant variations in their mechanical properties
      (bending rigidity), particularly in the proximal and distal sections. It is
      important that the surgeon become familiar with the individual characteristics of
      strength and rigidity for the particular devices available and how these might
      impact fracture healing. Consideration of this information could alter the
      decision to select one system over another in a complex fracture situation.

PMID- 9553857
TI  - Reamed intramedullary femoral nailing after induction of an "ARDS-like" state in
      sheep: effect on clinically applicable markers of pulmonary function.
AB  - OBJECTIVES/HYPOTHESIS: At present, the optimal treatment for appropriately
      resuscitated, multiply injured patients includes fixation of long bone fractures
      within twenty-four hours of injury. This management approach has been shown to
      decrease the incidence of pulmonary complications, multiple organ failure, and
      death. Some investigators have hypothesized that acute reamed intramedullary
      nailing of the femur (RIMNF) may result in pulmonary dysfunction as a result of
      the pulmonary fat embolization generated during this procedure. Patients with
      concomitant thoracic trauma may be at particular risk for this potentially severe
      complication. In an attempt to determine whether RIMNF can be safely carried out
      regardless of the severity of a pulmonary injury, we monitored the pulmonary
      effects of RIMNF in sheep in which an acute respiratory disorder (ARDS)-like
      state had been induced. Our hypothesis was that, if the pulmonary fat
      embolization that occurs as a result of RIMNF has a clinically significant
      effect, it would be detectable in an animal model in which a severe lung injury
      had been induced prior to the start of RIMNF. STUDY DESIGN: This was an acute
      experimental procedure performed on yearling sheep. METHODS: Reamed
      intramedullary nailing of the femur was performed in two groups of instrumented
      sheep. The first group had no pulmonary injuries. The second group had an ARDS
      like state induced by intravenous infusion of perilla ketone prior to RIMNF.
      Perilla ketone increases pulmonary microvascular permeability without changing
      filling pressures and is used to induce a model of human ARDS. Hemodynamic and
      oximetric parameters were measured or calculated, as was pulmonary dynamic
      compliance during the experiment. RESULTS: Infusion of perilla ketone caused a
      significant pulmonary injury. RIMNF caused no additional significant effect on
      intrapulmonary shunt, mixed venous oxygen saturation, or dynamic compliance,
      which are clinically used to assess the severity of pulmonary dysfunction in
      injured patients. CONCLUSIONS: The fat embolization that occurs during RIMNF in
      an appropriately resuscitated sheep has no clinically significant effect on
      pulmonary function, even in the setting of a severe pulmonary dysfunction.

PMID- 9553856
TI  - Femur fractures in chest-injured patients: is reaming contraindicated?
AB  - OBJECTIVE: To determine if reamed femoral intramedullary nailing increases the
      pulmonary complications seen in chest-injured patients. DESIGN: Retrospective
      review of prospectively collected trauma database data from January 1991 to
      October 1994. SETTING: Methodist Hospital, Indianapolis, Indiana, Level I Trauma
      Center. PATIENTS: Group I: Chest-injured patients [chest Abbreviated Injury Score
      (AIS) > or = 2] without femur or tibia fractures. Group II: Chest-injured
      patients (chest AIS > or = 2) with femoral reamed intramedullary fixation. Group
      III: Chest-injured patients (chest AIS > or = 2) with femoral shaft fixation
      using nonreamed fixation (rush rods, plating, or external fixation). Group IV:
      Non-chest-injured patients (chest AIS < 2) with femoral reamed intramedullary
      fixation. MAIN OUTCOME MEASUREMENT/HYPOTHESIS: Reamed femoral intramedullary
      nailing does not alter pulmonary outcomes, even in chest-injured patients.
      RESULTS: Groups I and II had a very similar incidence of adult respiratory
      distress syndrome (ARDS), pneumonia, and number of ventilator days. Group III had
      a significantly higher incidence of ARDS and number of ventilator days than did
      Group I or II. Group III did not have a chest AIS score significantly different
      than Groups I and II. Group II had significantly higher ARDS and more ventilator
      days than did Group IV when only analyzing raw data. When injury severity was
      adjusted, there were no significant differences in pulmonary outcomes.
      CONCLUSION: Reamed intramedullary femoral fixation did not increase pulmonary
      morbidity in chest-injured patients.

PMID- 9553859
TI  - Mechanical complications associated with the use of the unreamed AO femoral
      intramedullary nail with spiral blade: first experiences with thirty-five
      consecutive cases.
AB  - OBJECTIVE: To evaluate the unreamed femoral nail with spiral blade (UFN-SB) in
      the treatment of subtrochanteric femur fractures. DESIGN: Retrospective review of
      a consecutive series of twenty-eight fractures. Sixteen patients had metastatic
      disease. SETTING: Academic teaching hospital. MAIN OUTCOME MEASURES: Clinical and
      radiographic examination. RESULTS: Five mechanical complications were observed in
      four patients. In one patient with a metastastic fracture, we noted a breakage of
      the SB twice. In patients with traumatic subtrochanteric fracture, migration of
      the SB was observed three times, needing reintervention twice. CONCLUSIONS:
      Although this implant is useful in the treatment of subtrochanteric femur
      fractures, it is our contention that the problem of subtrochanteric fracture
      fixation is not solved with this implant, especially in elderly osteoporotic
      patients who require early weight bearing.

PMID- 9553860
TI  - Removal of a broken Synthes proximal spiral blade.
AB  - Use of cephalomedullary nails is an option for treatment of subtrochanteric femur
      fractures. However, the magnitude of bending forces in this area of the femur
      often can lead to implant failure before union. We report on a case of hardware
      failure of a specific device (Synthes spiral blade) and a method for removal.

PMID- 9553861
TI  - Effects of degrees of reaming on healing of segmental fractures in rats.
AB  - OBJECTIVE: To assess the effects of graded intramedullary reaming and nailing on
      the healing pattern of segmental diaphyseal fractures using male Wistar rats.
      STUDY DESIGN: In male Wistar rats we produced two standardized, partial
      osteotomies with an eight-millimeter intermediary fragment in the femoral
      diaphysis. The osteotomies were subsequently manually broken. In Group A,
      intramedullary reaming was performed to 1.6 millimeters, and the fracture was
      stabilized with a 1.6-millimeter steel pin. In Group B, the femoral canal was
      reamed to 2.0 millimeters, and a hollow steel tube of 2.0 millimeters was
      installed. The rats were allowed free movement. After four, eight, and twelve
      weeks, eight rats in each group were sacrificed and callus formation,
      biomechanical properties, and bone blood flow were evaluated. RESULTS: The callus
      area was relatively constant with time in Group B, whereas a reduction was
      observed in Group A at twelve weeks. The biomechanical properties increased
      throughout the experimental period in both groups, and no significant differences
      between the groups were detected in bending moment, bending rigidity, or fracture
      energy. Total bone blood flow was substantially increased at four weeks in both
      groups and decreased throughout the experimental period. In addition, blood flow
      of the segmental fractured area was substantially increased after four weeks and
      decreased gradually thereafter. The increases in blood flow tended to be largest
      in the moderately reamed group. CONCLUSION: This study indicates that the degree
      of reaming does not significantly affect the healing pattern measured as
      restoration of mechanical characteristics.

PMID- 9553862
TI  - Ultrasound for the early diagnosis of tibial fracture healing after static
      interlocked nailing without reaming: histologic correlation using a canine model.
AB  - OBJECTIVE: Ultrasound is thought to be clinically useful in evaluating bone
      formation through its presumed identification of fracture callus. However,
      documentation of the actual histology of the tissue identified by ultrasound has
      been lacking. The purpose of this study was to determine the histologic
      composition of the hyperechoic tissue "seen" by ultrasound. STUDY DESIGN:
      Unilateral fractures were created in eight canine tibias and then fixed by using
      locked intramedullary nailing without reaming. The limbs were studied at two,
      three, four, six, and eight weeks postoperatively with plain radiographs,
      ultrasound, and ultrasound-directed needle biopsy. RESULTS: The presence of a
      hyperechoic ultrasound signal was found to have a 100 percent correlation with
      the presence of hard fracture callus biopsy tissue. In addition, fracture union
      by ultrasound criteria significantly predated radiographic fracture union (5.6
      vs. 7.3 weeks, p = 0.05). CONCLUSIONS: These results support and provide a
      scientific basis for the clinical use of ultrasound to assess tibial fracture
      healing following static interlocked nailing without reaming.

PMID- 9553863
TI  - Ultrasound for the early diagnosis of tibial fracture healing after static
      interlocked nailing without reaming: clinical results.
AB  - OBJECTIVE: Based on the results of a pilot study indicating the potential value
      of ultrasound (US) as a diagnostic tool for the early assessment of fracture
      healing and the related need for secondary operative procedures in patients
      treated by statically locked intramedullary (IM) nailing without reaming, a
      protocol was established for a larger scale prospective trial. The purpose of
      this study was to evaluate the outcome of this follow-up trial. DESIGN/METHODS:
      All skeletally mature patients admitted to the Henry Ford Hospital (Detroit,
      Michigan) from January 1993 to August 1994 who had sustained an acute fracture of
      the tibial shaft and who were treated by statically locked IM nailing, without
      reaming, were candidates for study. Forty-seven patients with fifty fractures
      that could be evaluated by US were included. The adopted determinants for
      fracture healing were complete disappearance of the IM nail on US examination
      performed at six weeks postoperatively, or progressive disappearance of the nail
      noted between the initial six-week study and a second nine-week US examination,
      both in conjunction with periosteal callus formation. Radiographs were obtained
      to monitor maintenance of reduction and to further evaluate fracture healing.
      RESULTS: Of thirty-eight fractures with a positive US (thirty-two at six weeks,
      six at nine weeks), thirty-seven healed uneventfully, a positive predictive value
      of 97 percent. Radiographic fracture healing was not evident until, on average,
      nineteen weeks after injury. The single false-positive fracture progressed to
      nonunion. Of the twelve fractures with negative US studies, ten underwent
      secondary procedures (nine dynamization, one bone graft), with four progressing
      to nonunion. Two patients refused secondary surgery; screw failure occurred in
      both. Otherwise, there were no hardware failures in this series. CONCLUSIONS: The
      results of this study indicate that US may provide important prognostic
      information concerning fracture healing after unreamed tibial nailing, upon which
      subsequent treatment can be based.

PMID- 9553864
TI  - Infections in periarticular fractures of the lower extremity treated with
      tensioned wire hybrid fixators.
AB  - OBJECTIVES: To observe the incidence and clinical presentation of infection in
      periarticular fractures of the tibia and femur treated with tensioned wire
      external fixators. DESIGN: Prospective cohort study. SETTING: Level One Trauma
      Center in urban community. Single surgeon. PATIENTS: One hundred thirty-five
      patients with 145 fractures: seventy tibial plateau, fifty-six pilon, and
      nineteen distal femur. Five-year treatment period, 1991 to 1995. MAIN OUTCOME
      MEASUREMENTS: The incidence of infection was evaluated. RESULTS: Nineteen of 145
      fractures (13 percent) were complicated by infection. Infections presented as pin
      tract inflammation requiring intravenous antibiotics (seven), deep infection
      requiring debridement and removal (five), septic arthritis (three), deep fracture
      infection (three), and necrotizing fasciitis (one). CONCLUSIONS: Infection is a
      common complication of juxtaarticular fractures treated with tensioned wire
      fixators. Excellent pin care is required. Aggressive management of infections
      with intravenous antibiotics and debridement will resolve infections occurring in
      patients treated with tensioned wire fixators. Septic arthritis is associated
      with wires placed less than one centimeter from the subchondral bone. Deep
      infection is associated with insidious swelling and excessive proliferative
      callus. Wire infections increase with prolonged frame time.

PMID- 9553865
TI  - Technical notes on a radiolucent distractor for indirect reduction and
      intramedullary nailing.

PMID- 9553866
TI  - Coordinate production of PGE2 and IL-1 beta in the gingival crevicular fluid of
      adults with periodontitis: its relationship to alveolar bone loss and disruption
      by twice daily treatment with ketorolac tromethamine oral rinse.
AB  - The inflammatory mediators prostaglandin E2 (PGE2) and interleukin-1 beta (IL-1
      beta) play critical roles in the inflammatory process leading to alveolar bone
      and connective tissue loss in periodontal disease. Data from a previously
      published 6-month clinical study demonstrated that twice daily use of 0.1%
      ketorolac tromethamine oral rinse prevented alveolar bone loss in adults with
      periodontitis. We further analyzed data from this study to examine the
      relationship between PGE2. IL-1 beta and bone loss. Patient mean PGE2 and IL-1
      beta levels in gingival crevicular fluid (M-GCF) measured throughout the course
      of the study were directly compared to the maximum amount of alveolar bone height
      loss observed at a single study site in each patient. The maximum amount of bone
      loss measured was chosen for the analysis since the pattern of bone loss was
      clearly episodic in nature. A statistically significant correlation (r = 0.73, p
      = 0.001) exists between M-GCF PGE2 concentration and the maximum amount of bone
      height lost at individual patient study sites. The correlation between M-GCF IL-1
      beta concentration and maximum bone height lost is also statistically significant
      (r = 0.66, p = 0.005). Over the 6-month duration of the study, both PGE2 and IL-1
      beta were coordinately expressed in the placebo treatment group as reflected in
      the significant correlation between M-GCF concentrations of the 2 mediators (r =
      0.81, p < 0.001). Treatment of patients with 0.1% ketorolac tromethamine twice
      daily for 6 months resulted in reductions of PGE2 in GCF and a negligible
      correlation between M-GCF PGE2 and M-GCF IL-1 beta (r = 0.42, p = 0.088). This
      lack of a strong association between the 2 mediators in the ketorolac treatment
      group provides a direct biochemical readout of the anti-inflammatory efficacy of
      ketorolac tromethamine oral rinse in patients with periodontitis. Further studies
      are warranted to determine the full diagnostic potential of M-GCF levels of PGE2
      and IL-1 beta for predicting risk of alveolar bone loss in patients with
      periodontitis and monitoring periodontal therapy effectiveness.

PMID- 9553867
TI  - The regulation of fiber arrangement in advanced cellular cementogenesis of human
      teeth.
AB  - This study observed cellular cementum in fully formed human premolars by light
      and electron microscopy to elucidate how cementoblasts regulate the fiber
      arrangement in cementum. Cementoblasts had wing-like processes encircling the
      principal fibers, where Sharpey's fibers were dense. On the cementum-facing side,
      wing-like processes were segmented into finger-like processes in parallel with
      the cementum surface. Observations suggested that with the segmentation intrinsic
      fibers appeared around principal fibers in close association with finger-like
      processes. Where Sharpey's fibers were few or absent, where intrinsic fibers were
      the main fibrous element of the cementum, cementoblasts had only few or no wing
      like processes, but had finger-like processes not associated with the wing-like
      processes on the cementum-facing side. On the basis of the origin of the finger
      like processes the main results suggest that there are two kinds of
      cementoblasts: one has finger-like processes associated with wing-like processes
      and secretes intrinsic fibers from the finger-like processes to incorporate the
      principal fibers for tooth support. The second type has finger-like processes not
      associated with wing-like processes, this type secretes intrinsic fibers from the
      finger-like processes to adjust the cementum thickness.

PMID- 9553869
TI  - A comparison of stereological and computer-assisted histomorphometric analysis as
      tools for histological quantification in regenerative studies.
AB  - This study was designed to compare computer-assisted histomorphometric analysis
      (CAHA) and stereology (STER) as measurement tools for evaluating the repair
      response during periodontal wound healing. Thirty-six histological sections
      derived from 4 surgically created defects in the furcation of mandibular second
      premolars of sheep were measured by each technique to determine the furcation
      area and volume, and the percentage of new bone formation at 7 wk
      postoperatively. Slides were viewed in random order with the source unknown to
      the examiner (JL). One section from each of the 4 specimens was flagged for
      triplicate measurement by each technique. Intraexaminer error was determined to
      be low as the coefficient of variation in each of the 2 techniques was between 1%
      and 4%. A consistently higher percentage of bone was identified using stereology.
      The coefficient of agreement was plotted to determine how closely these 2
      techniques were matched in their respective estimations of bone fill in a
      furcation defect. This analysis revealed statistical bias between the 2
      techniques and a low degree of agreement between them. This study demonstrates
      that the 2 techniques are not interchangeable. It also emphasizes that the reader
      must be cautious when comparing results from studies in which different systems
      of measurement and analysis have been used. Stereology was determined to be the
      measurement tool of choice due to its high degree of reproducibility, ease of use
      and efficient use of time.

PMID- 9553868
TI  - Killing of Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella
      intermedia by protegrins.
AB  - Protegrins are broad spectrum antibiotic peptides isolated from porcine
      leukocytes. In this study, we (i) examine the sensitivity of Gram-negative,
      anaerobic periodontal pathogens to synthetic protegrins; (ii) determine the
      relative potencies of protegrin congeners against these bacteria; and (iii)
      compare the potency of protegrins with other antibiotic peptides, including
      magainin MSI-78, tachyplesin I, cecropin P1, human defensins HNP-1-3, and
      clavanin A. Synthetic L- and D-enantiomers of protegrin 1 (PG-1 and D-PG-1,
      respectively), and L-enantiomers of protegrins 2, 3 and 5 (PG-2, PG-3 and PG-5)
      were tested against Fusobacterium nucleatum, and black-pigmented organisms
      including Porphyromonas gingivalis and Prevotella intermedia. Strains of both F.
      nucleatum and the black-pigmented organisms were sensitive to PG-1, and exhibited
      mean ED99 of 2.2-2.3 micrograms/ml and 3.4-9.9 micrograms/ml, respectively. The D
      form was statistically more potent than the L-form against these oral anaerobes,
      and although this difference in potency is unlikely to be of decisive therapeutic
      significance, the D-form may be of value given ability to resist microbial and
      host-derived proteases. PG-1 was more potent than magainin, tachyplesin,
      cecropin, defensins and clavanin under test conditions. Hypertonic salt
      concentrations and heat-inactivated serum were found to be inhibitory to the
      bactericidal activity of PG-1. PG-1 was found to induce morphologic alterations
      in the ultrastructural appearance of F. nucleatum consistent with damage to the
      bacterial membranes. We conclude that protegrins may be useful antimicrobial
      agents in therapy against Gram-negative anaerobic bacteria believed to be
      involved in chronic, adult forms of periodontal infections.

PMID- 9553870
TI  - Rapid chair-side DNA probe assay of Bacteroides forsythus and Porphyromonas
      gingivalis.
AB  - This study compared a rapid, colorimetric DNA probe assay designed to be
      performed in a dental office within 40 min, with anaerobic culture and indirect
      immunofluorescence microscopy (IFM) for detection of Bacteroides forsythus and
      Porphyromonas gingivalis in subgingival plaque samples. The DNA probe assay used
      the Periodontal Microbial Identification Test (Saigene Corporation, Bothell,
      Washington, USA). B. forsythus was detected in 46 (52%), 49 (55%) and 39 (44%) of
      the samples by DNA probe, culture (at levels > or = 10(5)) and IFM, respectively.
      P. gingivalis was detected in 24 (27%), 18 (20%) and 29 (33%) of the samples by
      DNA probe, culture (at levels > or = 10(5)) and IFM, respectively. Results from
      the DNA probe assay were compared to culture. Culture negative, probe positive
      samples were re-evaluated by IFM, and IFM positive samples were considered
      positive in "resolved" data. Using resolved data. DNA probe detection sensitivity
      and specificity values for B. forsythus were 81% and 91% and for P. gingivalis
      were 80% and 95%, respectively. DNA probe test results were further compared with
      culture and IFM. For samples negative by both culture and IFM, probe specificity
      was 92% in 25 B. forsythus samples and 95% in 57 P. gingivalis samples. For
      samples positive by both reference methods, probe sensitivity was 82% in 27 B.
      forsythus samples and 73% in 15 P. gingivalis samples. B. forsythus was detected
      more frequently by culture compared with IFM; the reverse was observed for P.
      gingivalis. The rapid DNA probe assay for B. forsythus and P. gingivalis was
      comparable to cultivable and IF analyses.

PMID- 9553872
TI  - Differential chemotactic effect of cementum attachment protein on periodontal
      cells.
AB  - Selective re-population of the root surface by periodontal ligament cells is
      considered a key factor in periodontal regeneration. A recently isolated cementum
      attachment protein (CAP) has been shown to enhance fibroblast attachment. In the
      present study the potential of CAP to selectively attract periodontal ligament
      cells (PLC) was studied in vitro in a micro-chemotaxis system. Human periodontal
      ligament cells and gingival fibroblasts (GF) were compared for their chemotactic
      response to either cementum attachment protein or to fibronectin. Murine dermal
      fibroblasts (MDF) served as control, irrelevant to the periodontium. The
      chemotactic response of PLC to fibronectin at 10(-8) M was of a similar magnitude
      as that of GF (16 +/- 5 and 11 +/- 3 cells/field, respectively), but both were
      significantly lower than the response of MDF (28 +/- 3 cells/field). The
      chemotactic response of periodontal ligament cells to the cementum attachment
      protein at 10(-7) M was higher (36 +/- 5 cells/field) than that of gingival
      fibroblasts or murine dermal fibroblasts (14 +/- 2 and 16 +/- 2 cells/field,
      respectively). These results suggest that cementum attachment protein can
      influence the selective re-population of root surfaces by periodontal ligament
      cells.

PMID- 9553873
TI  - Forced eruption technique: rationale and clinical report.
AB  - This article describes a refined, simplified forced eruption technique, and
      compared it with previous methods. This simplified method is easy to perform and
      encourages the use of adjunctive orthodontics in general practice. This
      relatively uncomplicated, quick, and cost-effective treatment can benefit
      patients.

PMID- 9553871
TI  - Type VI collagen is associated with microfibrils and oxytalan fibers in the
      extracellular matrix of periodontium, mesenterium and periosteum.
AB  - Type VI collagen was immunolocalized in several soft connective tissues at the
      light and electron microscopic level. Positive labeling was found in all tissues
      examined, periodontal ligament, gingiva, mesenterium and periosteum. The labeled
      structures could be divided into 2 categories: microfibrils intermingling with
      collagen fibrils, and those that formed bundles (oxytalan fibres and elastin
      associated microfibrils). Control sections incubated with antibody preabsorbed to
      purified type VI collagen, or with non-immune antibody, proved to be negative.
      Our observations indicate that the structural organization of type VI collagen
      varies from small microfibrillar structures associated with the collagen and
      elastin fibre systems to highly ordered parallel arrays of oxytalan bundles.

PMID- 9553874
TI  - An alternative treatment with the overlay removable partial denture: a clinical
      report.

PMID- 9553875
TI  - Acceptability of shade differences in metal ceramic crowns.
AB  - STATEMENT OF PROBLEM: Application of technology that quantify color and color
      differences is currently used in esthetic restorative materials research.
      However, parameters for the size of perceptible and acceptable color differences
      in metal ceramic crowns have not been determined. PURPOSE: The CIELAB
      colorimetric system was used to study the relationship between instrumentally
      measured color differences (delta E) and human observer assessment of color
      differences in metal ceramic crowns. MATERIAL AND METHODS: Subjects were shown
      pairs of metal ceramic crowns whose color difference varied from
      indistinguishable to obvious. The subjects attempted to discern a difference in
      each pair's color and indicated the clinical acceptability of the shade
      difference between the crown pairs. RESULTS: Correlations between instrumental
      and visual assessment of color differences in these crown pairs did not agree in
      all dimensions of color space. Thresholds acceptability of color differences were
      1.1 delta E units for red-varying crowns and 2.1 delta E units for yellow-varying
      crowns. Thresholds for perceptibility judgments were significantly lower than
      thresholds for acceptability judgments. CONCLUSIONS: Acceptability thresholds
      were found to be dependent on chromaticity. Observers were more sensitive and
      critical of crowns whose color differed in redness as opposed to crowns whose
      color differed to the same extent in yellowness.

PMID- 9553876
TI  - Microleakage of Class V compomer and light-cured glass ionomer restorations.
AB  - STATEMENT OF PROBLEM: Resin-modified (light-cured) glass ionomer and polyacid
      modified composite resin (compomer) restorations are popular choices for the
      restoration of root caries and cervical abrasion/erosion lesions, but clinical
      studies are relatively few and have been published primarily as abstracts.
      PURPOSE: In the absence of adequate clinical data, the marginal integrity of
      restorations of the above two types of material was compared in vitro. The
      microleakage of restorations of two light-cured glass ionomer restorative
      materials and of one compomer material was evaluated. METHODS AND MATERIAL:
      Restorations of the three materials were placed in facial and lingual Class V
      cavity preparations in bovine incisors. All preparations were centered on the
      cementoenamel junction and were prepared with 45-degree enamel bevels. After
      thermal cycling, teeth were immersed in methylene blue dye, then sections of the
      restorations (n = 16) were visually evaluated. RESULTS: Dye penetration was
      observed at approximately 20% of restoration margins for all three materials,
      with the greatest incidence of severe leakage in the compomer restorations.
      CONCLUSION: No significant difference in microleakage among the three materials
      (ANOVA; p > 0.05) was found.

PMID- 9553877
TI  - Microleakage along apical root fillings and cemented posts.
AB  - STATEMENT OF PROBLEM: Coronal leakage of endodontically treated teeth has been
      found to result in a high failure rate. PURPOSE: This study tested leakage along
      apical root fillings remaining after post space preparation and cemented posts in
      root canals. MATERIAL AND METHODS: A total of 120 human roots were used in the
      study and divided into six groups, 20 roots for each group. By using a modified
      fluid transport model, leakage (in microL/hr) along ParaPost dowels that were
      cemented in the coronal 7 mm of root canals with Fuji Duet, Ketac Cem, Panavia
      EX, or zinc phosphate cements was compared with that along the coronal 7 mm of
      conventional root canal fillings. Leakage along the apical 4 mm of root filling
      remaining after post space preparation was compared with that along the 11 mm
      root filling before post space preparation. RESULTS: More leakage was recorded
      along the apical 4 mm of root filling than along the 11 mm of original root
      filling (p = 0.0325). ParaPost dowels cemented with any test cement did not
      produce more leakage than the 7 mm coronal root filling (p = 0.2145).
      CONCLUSIONS: The apical 4 mm of root canal filling remaining after post space
      preparation leaks statistically significantly more than the original full-length
      root canal filling. The leakage created by removal of the coronal part of root
      canal filling during post space preparation may be compensated by the cemented
      posts.

PMID- 9553878
TI  - Resin to metal bond strengths using two commercial systems.
AB  - STATEMENT OF PROBLEM: A secure bond between resin and an alloy framework is
      necessary for clinical success in removable prosthodontics. PURPOSE: This study
      compared the shear bond strength of composite to composite to metal with two
      commercially available chemical bonding systems: a silicoating system
      (Silicoater) and a nitrogenous heterocycle-acrylonitrile system (Kevloc).
      MATERIAL AND METHODS: Fifty-two nickel-chromium cubes were cast and composite
      resin was bonded to the alloy surfaces according to manufacturer's directions.
      After storage at 35 degrees C for 15 days, and thermocycling at 5 degrees C and
      55 degrees C for 1200 cycles, the bonds were fractured in shear on a universal
      testing machine. RESULTS: Mean bond strength for the silicoated sample was 10.93
      MPa and for the heterocycle-acrylnitrate system 11.44 MPa. An unpaired t test
      revealed no difference between the groups (p = 0.60). Visual inspection of the
      fracture surfaces revealed that failure was adhesive at the resin-to-metal
      surface in almost all the specimens.

PMID- 9553879
TI  - Comparison of a new autocuring temporary acrylic resin with some existing
      products.
AB  - STATEMENT OF PROBLEM: Some problems of the self-curing or autopolymerizing resins
      may include color instability and dimensional inaccuracy. PURPOSE: This study
      compared the color and dimensional stability of the new autopolymerizing resin
      Unifast II, which combines a new activator with some existing products. RESULTS:
      The change in color (delta E value) of Unifast II resin was less than that
      demonstrated for four autopolymerizing resins (Unifast, Curefast, ADFA, and
      MIKY). Unifast II did not exhibit color change when stored in conditions below 37
      degrees C. Unifast II also had a significantly better fit than the other four
      autopolymerizing resins (p < 0.01). No significant differences in transverse
      strength were observed among Unifast II, Unifast, and ADFA, but the Unifast II
      autopolymerizing resin maintained its color stability and dimensional accuracy
      without sacrificing its transverse strength.

PMID- 9553880
TI  - New acrylic resin composite with improved thermal diffusivity.
AB  - STATEMENT OF PROBLEM: Studies have shown that physical characteristics of denture
      base materials may affect patient acceptance of denture prostheses by altering
      sensory experience of food during mastication. Thermal diffusivity is one
      material property that has been cited as being important in determining gustatory
      response, with denture base acrylic resins having low thermal diffusivity
      compared with denture base metal alloys. PURPOSE: This study prepared and
      characterized experimental acrylic resin composite material with increased
      thermal diffusivity. MATERIAL AND METHODS: Sapphire (Al2O3) whiskers were added
      to conventional denture base acrylic resin during processing to achieve loadings
      of 9.35% and 15% by volume. Cylindrical test specimens containing an embedded
      thermocouple were used to determine thermal diffusivity over a physiologic
      temperature range (0 degree to 70 degrees C). RESULTS: Thermal diffusivities of
      the sapphire containing composites were found to be significantly higher than the
      unmodified acrylic resin. Thermal diffusivity was found to increase in proportion
      to the volume percentage of sapphire filler, which suggested that the high aspect
      ratio ceramic particles formed a pathway for heat conduction through the
      insulating polymer matrix. CONCLUSION: The thermal diffusivity of denture base
      acrylic resin was increased by the addition of thermally conducting sapphire
      whiskers.

PMID- 9553881
TI  - Laser welding of a cobalt-chromium removable partial denture alloy.
AB  - STATEMENT OF PROBLEM: The electric alloy brazed joints of removable partial
      denture alloys have failed frequently after routine usage. PURPOSE: A technique
      providing higher joint strengths was investigated. This investigation compared
      the tensile strengths of electric-brazed and laser-welded joints for a cobalt
      chromium removable partial denture alloy. MATERIAL AND METHODS: Twenty-four
      cobalt-chromium standard tensile testing rods were prepared and divided into
      three groups of eight. All specimens in the control group (group 1) were left in
      the as-cast condition. Groups 2 and 3 were the test specimens, which were
      sectioned at the center of the rod. Eight specimens were joined by using electric
      brazing, and the remaining specimens were joined by using laser welding. After
      joining, each joint was ground to a uniform diameter, then tested to tensile
      failure on an Instron universal testing machine. Failure loads were recorded and
      fracture stress calculated. Statistical analysis was applied. RESULTS: The
      student-Newman-Keuls test showed a highly significant difference between the
      joint strengths of the as-cast control specimens, the electric-brazed and laser
      welded joints. CONCLUSIONS: The tensile strengths of the as-cast joints were
      higher than those for the laser-welded joints, and both were higher than the
      electric-brazed joint strengths.

PMID- 9553882
TI  - Effects of joint configuration for the arc welding of cast Ti-6Al-4V alloy rods
      in argon.
AB  - STATEMENT OF PROBLEM: Titanium and its alloys are more commonly used in
      prosthodontics and welding has become the most common modality for their joining.
      Studies on the welding of titanium and its alloys have not quantified this value,
      though its importance has been suggested. PURPOSE: This study compared the
      strength and properties of the joint achieved at various butt joint gaps by the
      arc-welding of cast Ti-6Al-4V alloy tensile bars in an argon atmosphere. MATERIAL
      AND METHODS: Forty of 50 specimens were sectioned and welded at four gaps. All
      specimens underwent tensile testing to determine ultimate tensile strength and
      percentage elongation, then oxygen analysis and scanning electron microscopy.
      RESULTS: As no more than 3 samples in any group of 10 actually fractured in the
      weld itself, a secondary analysis that involved fracture location was initiated.
      There were no differences in ultimate tensile strength or percentage elongation
      between specimens with weld gaps of 0.25, 0.50, 0.75, and 1.00 mm and the as-cast
      specimens. There were no differences in ultimate tensile strength between
      specimens fracturing in the weld and those fracturing in the gauge in welded
      specimens; however, as-cast specimens demonstrated a higher ultimate tensile
      strength than welded specimens that fractured in the weld. Specimens that
      fractured in the weld site demonstrated less ductility than those that fractured
      in the gauge in both welded and as-cast specimens, as confirmed by scanning
      electron microscopy examination. The weld wire showed an oxygen scavenging effect
      from the as-cast parent alloy. CONCLUSIONS: The effects of the joint gap were not
      significant, whereas the characteristics of the joint itself were, which
      displayed slightly lower strength and significantly lower ductility (and thus
      decreased toughness). The arc-welding of cast titanium alloy in argon atmosphere
      appears to be a reliable and efficient prosthodontic laboratory modality
      producing predictable results, although titanium casting and joining procedures
      must be closely controlled to minimize heat effects and oxygen contamination.

PMID- 9553883
TI  - Radiographic verification of implant abutment seating.
AB  - STATEMENT OF PROBLEM: It is possible to incorrectly seat an abutment on an
      external hex implant. PURPOSE: This study investigated the theoretical and
      practical limits of radiographic verification of the complete seating of implant
      abutments on external hex implants. MATERIAL AND METHODS: A positioning device
      that could accurately place the film and/or tube head in any vertical relation
      desired relative to the implant and abutment was fabricated. For all records, a
      standard abutment was secured to the implant in both a fully seated position
      (closed) and with the abutment turned approximately 30 degrees and seated atop
      the implant external hex (open). Digital radiographs were made with the tube head
      fixed perpendicular to the implant and the film angled at 0, 5, 10, 15, 20, 25,
      30, 35, 40, and 45 degrees. The film was then positioned parallel to the implant
      and the tube head was angled at 0, 5, 10, 15, 20, 25, 30, 35, 40, and 45 degrees.
      An image of each position was shown to 36 dentists and they were asked if the
      image was diagnostic for determining the status of the implant/abutment
      interface. RESULTS: The data were analyzed with a computer statistics program.
      The group with the tube head changed was analyzed with the Cochran's Q test and
      revealed a statistically significant (p < 0.0001) change in the diagnostic value
      of radiographs beginning at 20 degrees. The group with the film angle changed was
      analyzed with a Pearson chi-square and showed no statistical difference (p =
      0.394) for the diagnostic value of any of the film angles. CONCLUSION:
      Maintaining the tube head to less than 20 degrees from perpendicular to the long
      axis of the implant resulted in a diagnostic radiograph, regardless of the angle
      of the film.

PMID- 9553884
TI  - Osseointegrated implants and orbital defects: U.C.L.A. experience.
AB  - PURPOSE: A clinical study of 23 craniofacial implants placed in 8 irradiated and
      nonirradiated orbital detects was conducted over a 7-year period. MATERIAL AND
      METHODS: Implant-retained orbital prostheses were fabricated, implant success
      rate was determined, and the soft tissue responses were recorded at 6-month
      intervals. As a result of patient death, no data were gathered on three implants.
      A five-point scale was used to record the health of the peri-implant soft tissues
      and the patients were followed from 9 to 72 months. The unit of measure was a
      visit/site that was assigned for each instance an implant site was evaluated.
      Evaluations were conducted at 6-month intervals, and for the study period, there
      were 80 visit/sites. RESULTS: The study revealed that 42.5% (34/80) of the
      visit/sites demonstrated an absence of inflammation; 23.7% (19/80) of visit/sites
      demonstrated slight redness; 13.8% (11/80) demonstrated peri-implant red and
      moist tissues; 6.2% (5/80) demonstrated granulation tissue associated with the
      implants; and 13.8% (11/80) infection of the peri-implant soft tissues was noted.
      Implant success rate was 35% (7/20); implant success rate in the nonradiated
      patients was 37.5% (3/8) and the success rate for radiated patients was 33.3%
      (4/12). Implants placed in the orbital region demonstrated a high failure rate.
      Most implant failures occurred late as opposed to early in the study period.
      CONCLUSION: Orbital implants should be placed in patients who understand that
      long-term success rates may be low and require meticulous hygiene maintenance.

PMID- 9553887
TI  - A comparison of maxillary and mandibular bone mineral densities.
AB  - STATEMENT OF PROBLEM: The success rate of implant osseointegration is dependent
      on many factors such as bone mineral density, volume and vascularity of bone,
      implant design, ridge shape, and patient selection criteria among others.
      PURPOSE: This study examined whether a technique to measure differences in bone
      mineral density in the maxilla and mandible might be useful to predict the
      likelihood of successful osseointegration. MATERIAL AND METHODS: Bone
      densitometry of the jaws was performed with a densitometer, and bone mineral
      density was calculated at three regions of the maxilla and one site in the
      mandibular body in 39 edentulous subjects. RESULTS: Significant differences were
      found between the mean bone mineral density of each site when compared with the
      three other locations. The mean bone mineral density for the mandible (mean =
      1.11 g.cm-2), was twice that of the anterior maxilla (mean = 0.55 g.cm-2). Both
      were significantly greater than the bone mineral density of the posterior maxilla
      (mean = 0.31 g.cm-2; including the hard palate, mean = 0.45 g.cm-2). The bone
      mineral densities at the three maxillary sites were all highly correlated (r > or
      = 0.78, p < 0.001). CONCLUSION: The dissimilarity in bone mineral density at
      different mandibular and maxillary sites may partly explain some variation in
      previously reported osseointegration rates. The posterior maxilla had the lowest
      bone mineral density and in certain circumstances before implant insertion, bone
      augmentation, or guided tissue regeneration may be advisable to improve the rate
      of osseointegration. Because the radiation dose is low, dual energy x-ray
      absorptiometry may be a useful noninvasive technique for determining the bone
      mineral density before implant insertion.

PMID- 9553886
TI  - Dental extractions after radiation therapy in the head and neck area and hard
      tissue replacement (HTR) therapy: a preliminary study.
AB  - STATEMENT OF PROBLEM: Dental extractions in patients who had radiation therapy
      for cancer in the head and neck region carry with them the risks of delayed
      healing, prolonged alveolar bone exposure, infection, and osteoradionecrosis.
      Among the precautions to minimize these risks are antibiotic coverage, limited
      extractions at any one time, soft tissue closure, and hyperbaric oxygen
      treatment. Rapid epithelization and minimal bone exposure are essential after
      extractions in irradiated patients. PURPOSE: This study examined the effects of
      hard tissue replacement on head and neck cancer patients who were treated with
      radiation therapy. MATERIAL AND METHODS: In a series of eight patients who had
      radiation doses from 4000 cGy to 7440 cGy in the head and neck area and who had
      44 teeth extracted, hard tissue replacement material mixed with tetracycline
      powder was placed in the extraction sites. RESULTS: Of the 44 teeth extracted, 19
      mandibular molars and premolars were in the direct field of radiation in seven
      patients. One patient also had 6 mandibular anterior teeth and 12 maxillary teeth
      extracted that received minimal radiation exposure. One patient had 6 mandibular
      anterior teeth extracted that were not in the area of direct exposure. One
      patient had a mandibular first molar extracted in an area that received minimal
      radiation exposure. Clinically, complete epithelization occurred in all patients.
      No infections developed. Radiographically no bone dissolution could be identified
      in the extraction area(s). The follow-up times ranged from 7 months to 18 months
      when the patients were seen last. CONCLUSION: The hard tissue replacement
      particles appears to provide a matrix for fibrous connective tissue formation.

PMID- 9553885
TI  - Obturator prostheses after cancer surgery: an approach to speech outcome
      assessment.
AB  - PURPOSE: This article describes a speech assessment protocol for patients using
      either obturator prostheses or speech aid prostheses for surgically acquired
      defects due to cancer of the maxilla and/or soft palate. METHODS: This protocol
      is structured according to the executive summary of "Disability in America:
      Toward a National Agenda For Prevention" a report formulated by the Institute of
      Medicine that describes four levels of disorder: (1) pathology, (2) impairment,
      (3) functional limitation, and (4) disability. Assessment instruments included
      (1) the Sentence Intelligibility Test to measure the rate and understandability
      of speech, (2) a speech physiology system to measure appropriate separation of
      the nasal/nasopharyngeal and oral compartments, (3) a 13-point interval scale to
      rate speech nasality, and (4) a scale to rate self-perceptions of communication
      effectiveness. RESULTS: The results from two patients are reported to illustrate
      the outcome assessment protocol.

PMID- 9553888
TI  - The influence of abutment angulation on strains and stresses along the
      implant/bone interface: comparison between two experimental techniques.
AB  - STATEMENT OF PROBLEM: Preangled abutments produce different stress distribution
      compared to straight abutments. PURPOSE: The objectives of this study were to (1)
      test the hypothesis that preangled abutments produce different stress
      distribution than straight abutments by using strain gauges attached to implants
      embedded in a medium simulating bone to determine strain distribution along the
      implant/bone interface; (2) test this hypothesis by photoelastic method; and (3)
      compare the two experimental techniques. MATERIALS AND METHODS: Five Integral
      Omniloc cylindrical implants 13 x 4 mm were polished to remove the hydroxyapatite
      coating, then six linear miniature strain gauges were attached, three on each
      side of the implant's surface. Two similar implants were embedded in a
      photoelastic material. Three abutments, straight, 15 degrees, and 25 degrees,
      were connected to each implant; strain versus applied compressive forces were
      recorded. Strain response to force parameter was defined as the slope of the
      strain-force curve. Isochromatic fringe patterns were also recorded. RESULTS: The
      strain gauge measurements showed higher, threefold and 4.4-fold, compressive
      strain concentration in the coronal zone of the implant when 15-degree and 25
      degree angulated abutments were used, respectively, compared with the straight
      abutment; whereas the photoelastic method showed an increase of only 11% in
      fringe order. Tensile strains were also measured from the coronal contralateral
      position on the implant, where photoelastic models did not show a change in
      stress type. CONCLUSIONS: Data obtained from strain gauges bonded to implants
      embedded in a medium can represent a precise simulation of the clinical condition
      when analyzing stress distribution along the implant/ bone interface.
      Photoelasticity provides different information and therefore should be regarded
      as a complementary method.

PMID- 9553889
TI  - Thermal modeling of laser welding for titanium dental restorations.
AB  - STATEMENT OF PROBLEM: Concerns of laser welding for titanium dental prostheses
      are the limited depth of laser beam penetration and extensive surface damage.
      PURPOSE: This study used numerical heat transfer simulation to explain this
      behavior and offers an alternate multiple-pulsed method. MATERIAL AND METHODS: A
      one-dimensional finite difference analysis was used to simulate heat transfer in
      pure titanium and gold during laser welding with a custom-constructed software
      program. RESULTS: The thermal gradient profiles revealed the problem to be
      inherent in titanium's low thermal conductivity; gold did not have this problem.
      Time-elapsed multiple pulses on titanium relieved this problem by giving the
      energy time to diffuse into the depth of the material. CONCLUSIONS: With single
      pulse laser irradiation on titanium, an increase in power could not greatly
      increase melting depth. The excess energy only vaporized the material surface.

PMID- 9553891
TI  - An esthetic and hygienic approach to the use of intracoronal attachments as
      interlocks in fixed prosthodontics.
AB  - This article describes a procedure that uses the Ney MS (Minimal Space)
      intracoronal attachment as an interlock in a pontic. This procedure overcomes the
      disadvantages associated with the use of the intracoronal attachments, which are
      (1) excessive tooth reduction often required to place the attachment within the
      contour of the crown; (2) compromised embrasures, which result in oral hygiene
      and periodontal problems; and (3) poor esthetics.

PMID- 9553890
TI  - A study of the classification and treatment of noncarious cervical lesions by
      general practitioners.
AB  - PURPOSE: This study presented a survey to determine what general practitioners in
      Nova Scotia perceived to be the cause of noncarious cervical lesions, and to
      ascertain their most frequent method of treatment. METHODS: The survey was
      completed by 63% of the 343 dentists polled. RESULTS: Ninety-four percent
      classified the lesion as abrasion, and 66% rated toothbrushing as the most likely
      cause. Treatment methods were varied, with no clear preference. CONCLUSION: The
      most frequently used restorative materials were GI/composites (29%) and
      composites (27%). The results of the survey suggest that treatment provided for
      noncarious cervical lesions may not be based on the correct diagnosis.

PMID- 9553893
TI  - A device to prevent jaw clenching.
AB  - This article describes a device that is intended to prevent the clenching of the
      teeth. The principle involved is that to clench the teeth for an extended period,
      an intraoral vacuum must be formed and maintained. A tube or drinking straw held
      between the lips extending out of the mouth will prevent a vacuum. The article
      explains and illustrates how such a device can be made that will exploit this
      principle. Disadvantages and advantages are discussed.

PMID- 9553892
TI  - Use of aluminum strips to fabricate verification jig for an implant-supported
      fixed partial denture.
AB  - Verification of the accuracy of the master cast for an implant-supported fixed
      partial denture will reduce the chair time and laboratory costs of implant
      prosthodontic treatment. A wire is usually luted in the mouth to machined
      components that have been secured to the implants, and the luted assembly is then
      transferred to the cast to evaluate the positional accuracy of the implant
      analogs. Unless this wire is dead soft, inaccuracies as a result of elastic
      memory of the wire can occur. Also, if the wire is not completely rigid, it can
      be distorted during handling. This article describes a more reliable verification
      jig for an implant-supported fixed partial denture that can be fabricated with
      1.5 mm thick aluminum strips that are luted to the implant components. The use of
      two aluminum strips creates a metal framework that is rigid and not easily
      distorted. Also the aluminum pieces do not have elastic memory because they were
      cut and not bent to shape.

PMID- 9553894
TI  - A simple method for obtaining a uniform thickness for long-term soft denture
      linings.
AB  - The thickness of long-term soft denture linings influences both their compliance
      and durability. Increasing the thickness of the lining material increases its
      perceived softness but makes the restoration more likely to fail through
      weakening of the acrylic resin denture base. Such effects have led to broad
      recommendations as to an appropriate thickness, advice that assumes a constant
      thickness of the lining material within the same denture. Several procedures used
      to produce such a constant thickness have been described. The necessary spacer is
      produced by manually adapting materials in their plastic state to the cast. Such
      procedures are liable to distortion and variation in spacer thickness and can be
      considered unreliable. This article describes a method for obtaining a uniform
      thickness of soft denture lining through the use of a vacuum-formed,
      thermoplastic blank as a spacer. The method is simple, applicable to all ridge
      forms, and reliably results in a soft lining of a known, uniform thickness. The
      method can be applied to long-term soft linings placed in both old and newly
      fabricated dentures. The spacer can be modified to allow variations in the
      prescribed extension of the soft lining within the denture base.

PMID- 9553895
TI  - Provisional retention of a removable partial denture during fabrication of a root
      retained overdenture.

PMID- 9553896
TI  - Enhanced stability for implant-supported overdenture record bases.

PMID- 9553897
TI  - Fabrication of an acrylic resin device used to increase the size of toothbrush
      handles.

PMID- 9553898
TI  - Computer-printer denture microlabeling system.
AB  - This procedure is easy to use and is cost-effective because it uses equipment
      that exist in any office or institution. The material used, transparency film for
      use with plain paper copier, is less expensive than either photographic slide
      film or normal slide films. Moreover, the transparency sheet can be used again
      for photocopying until the sheet is fully used up. There is no added cost of
      development of film, or is it necessary to wait for the whole roll of film to be
      used before the label can be retrieved and used. The background of the label is
      clear and only the black images of the characters of the label can be clearly
      seen. The effect of the transparency film, photocopy ink, and adhesive glue is
      not known. But no adverse effects have been noted. Microlabels have advantages
      over conventional labels with characters in font size 8 to 12, because more
      information, such as the full name of the patient, sex, country of origin, and
      national identification number can be incorporated. With more detailed
      information, quick identification of a deceased person can be made. Microlabels
      with a clear background will have minimal esthetic impact on the patient. The
      disadvantages of the technique is that it may not withstand a fire. In situations
      where the deceased body is badly burned, the denture and its identification strip
      may be burned, too. However, this risk can be minimized by placing the strip in
      the most posterior part of the denture-palatal in the maxillary denture and
      distal lingual in the mandibular denture. For testing of durability, dentures
      with the labels were placed in water for up to 4 months. The labels showed no
      sign of fading or deterioration.

PMID- 9553899
TI  - Curriculum integration in nutrition and mathematics.
AB  - Today's school-aged children face a multitude of health issues that affect their
      well-being and academic performance. Partnerships have developed between health
      and education agencies to help American children succeed at math and science and
      to prepare them to make healthful, lifelong decisions. Curriculum integration
      provides a framework for children to apply knowledge from several disciplines and
      to use this knowledge to solve real-life problems at work and at play. Goals for
      instruction focus on the needs not only of the individual but also of society.
      Nutrition science and mathematics form a natural partnership. Nutrition science
      incorporates numerous mathematical concepts and procedures such as sorting,
      classifying, statistics, probability, estimation, and rates and proportion. In
      preparation for participation in a global and technological society that will
      require citizens to be quantitative thinkers, educators must endeavor to assist
      all children in becoming adults who are mathematically literate and competent.

PMID- 9553900
TI  - Gambling behavior of students in grades seven and eight in Alberta, Canada.
AB  - This article reports results from a survey of gambling activities of seventh and
      eighth grade students in northeastern Alberta, Canada. Results confirmed that
      gambling practices are common among young adolescents. During the 12 months
      preceding the survey, virtually all respondents (98%) had gambled. Playing
      scratch tickets was the gambling activity most often played by young adolescents,
      followed by bingo. Boys were more likely than girls to engage in all forms of
      gambling activities. Sports betting and wagering on games of skill dimension were
      mostly male domains, whereas games of chance were female pursuits. Survey
      implications for public health officials are discussed.

PMID- 9553901
TI  - School Health Nursing Services Progress Review: report of 1996 national meeting.
AB  - This is a report of the outcomes of an invitational meeting convened in 1996 by
      the Division of Adolescent and School Health at the Centers for Disease Control
      and Prevention (DASH/CDC) and the National Center for School Health Nursing,
      American Nurses Association, Participants reviewed progress made on seven
      critical needs identified in 1994 at the School Health Nursing Services:
      Exploring National Issues conference. Priority actions were updated, consensus
      was reached for specific strategies to move towards achievement of goals and
      organizations and agencies were suggested to assume leadership. Participants and
      current membership of the National Nursing Coalition for School Health are listed
      as well as examples of related activities occurring in the interim. Collaborative
      partnerships are encouraged to assist school nurses in meeting the school-related
      health needs of all students.

PMID- 9553902
TI  - Health practices of educators participating in an Idaho wellness conference: one
      year follow-up.
AB  - The Great Potato Health Conference (GPHC), which convenes annually in Idaho, is
      one of more than 25 statewide wellness conferences for K-12 school personnel.
      This follow-up study assessed the health practices of conference participants one
      year following the GPHC. A 25-item health behavior instrument was administered to
      68 school district personnel prior to attending the GPHC and again three months,
      six months, and one year following the conference. Data were analyzed using a
      repeated measures one-way factorial analysis of variance to test for differences
      in the health practices of participants over time. Results indicated
      statistically significant main effects for both previous conference attendance
      and time of measurement. No statistically significant interaction effect occurred
      between previous conference attendance and time of measurement.

PMID- 9553903
TI  - The School Health Innovative Programs: integrating school health and managed care
      in San Diego.
AB  - Managed care organizations (MCOs) are being recruited to support school health
      services delivered in school clinics. Schools without clinics already provide
      numerous health services and could provide more if they had support from managed
      care organizations. This article describes the first two years of a San Diego
      based collaborative consisting of MCOs, school districts, and other health care
      agencies. By establishing trust, developing overriding principles, and creating
      an interagency communication infrastructure, this collaborative has encouraged
      shared management of many student health issues. Because the agreements apply to
      all schools, programs can reduce high rates of absenteeism district-wide and
      avoid unnecessary doctor appointments for common health problems. These
      collaborative agreements are designed to be financially self-sustaining. However,
      data collection, the logistics of obtaining parental consent, and getting health
      professionals to communicate with each other in new ways remain to be significant
      challenges.

PMID- 9553904
TI  - Evaluation of a three-year urban elementary school tobacco prevention program.
AB  - The longitudinal study compared effects of varying amounts of tobacco instruction
      (one, two, and three years) on the knowledge, attitudes, and behavioral
      intentions of urban elementary students. A three-year, fourth-through-sixth grade
      tobacco prevention curriculum was developed based on the Centers for Disease
      Control and Prevention's Guidelines for School Health Programs to Prevent Tobacco
      Use and Addiction. The curriculum comprised five, 45-minute lessons per year. The
      same trained instructor taught the curriculum all three years. Six intervention
      schools were taught the curriculum, and two control schools were not. A 49-item
      questionnaire was used to assess tobacco knowledge, attitudes, and behavioral
      intentions. The experimental group's posttest knowledge and attitude scores were
      significantly higher than the control group's posttest scores. No significant
      differences occurred in posttest behavioral intention scores between the control
      and intervention groups.

PMID- 9553905
TI  - Should school uniforms be mandated in elementary schools?

PMID- 9553906
TI  - Vitamin E: the radical protector.
AB  - Since its discovery and isolation the importance of vitamin E in maintaining
      normal physiologic processes and its value in treating various disease states
      have been the subject of much controversy. It was our intention to review and
      highlight some of the arguments and problems regarding the usefulness of vitamin
      E and to try to put them into proper perspective. The major area of interest
      concerning vitamin E lies essentially in its role in preventing damage caused by
      free radicals. The latter are now known to play an important role in radiation
      induced carcinogenesis, photoaging and photosensitization. The chemistry of
      vitamin E, its physiological function as a major antioxidant and its interaction
      with other antioxidants are described by the sum of animal studies, in vitro
      research and epidemiological investigations. In preparing the current data, it
      appeared that despite the controversy and conflicting results the body of
      literature as a whole judges vitamin E to be useful as an antioxidant. Although,
      in principle, the use of vitamin E can be quite advantageous, the manner of its
      administration, especially regarding topical application, remains unclear.

PMID- 9553908
TI  - A clinical survey of psoriasis in Italy: 1st AISP report. Interdisciplinary
      Association for the Study of Psoriasis.
AB  - BACKGROUND: Psoriasis is present all over the world and its prevalence varies in
      the different populations and different geographical areas. For example, Northern
      European countries seem to have rates of incidence which are greater than those
      known for Southern Europe. However, today there is still a lack of adequate data
      to allow comparisons at an international level. METHODS: In Italy in 1994 the
      AISP (Interdisciplinary Association for the Study of Psoriasis) co-ordinated the
      recording of monthly case histories and clinical results relating to psoriasis in
      patients observed in dermatology centres homogeneously distributed throughout
      Italy. The results were extrapolated from the overall case series. RESULTS: A
      sample of nearly 8000 cases was collected, most presenting psoriasis vulgaris.
      This pathology, prevalent in males, first appears at an age somewhere between the
      teens and twenties. Numerous factors may be involved, and onset is mainly
      attributed to stress, viral or bacterial infections and pharmacological therapy.
      Over 90% of cases lost between 1 and 7 working days in the course of the year.
      Local anti-psoriasis treatment in monotherapy was administered more frequently
      than systemic therapy or combined therapy. CONCLUSIONS: The results of this first
      Italian epidemiological study confirm that psoriasis is homogeneously distributed
      throughout the country. About 50% of patients avail themselves of specialist
      cures, even several times in the course of the year, and use a wide range of
      therapies which may be more or less demanding. The internal socio-economic cost
      of the disease is evident, particularly in terms of working days lost and/or
      medical expenses.

PMID- 9553907
TI  - Advances in the understanding of malignant transformation of keratinocytes: an
      immunohistochemical study.
AB  - AIM: We set out to investigate the interactions between malignant transformation
      of keratinocytes, presence of oncoproteins and immunosurveillance in squamous
      cell carcinoma (SCC) and in a preneoplastic lesion, actinic keratosis (AK).
      METHODS: Samples of SCC, AK and normal skin (NS) were subjected to quantitative
      analysis using the following antibodies: anti-p53, Ki67, OKT6, OK-DR, B7/BB1,
      anti-CD54, anti-CD11, OKT3, OKT4, OKT8; positivity for ras-p21, EGFr and bcl-2
      was evaluated by semiquantitative analysis. RESULTS: Oncoprotein alterations and
      increased keratinocyte proliferative activity were observed both in AK and SCC.
      The number of Langerhans cells (CD1a+ cells) was similar in the two lesions but
      lower in SCC compared to AK. The proportion of CD1a(+)-B7/BB1+ cells was slightly
      higher in AK and SCC than in NS. The Langerhans cells expressed the HLA-DR
      antigen in all groups. Values were highest in AK and NS, and quite low in SCC.
      Cytotoxic T lymphocytes were more numerous in SCC than in AK and NS.
      Interestingly, the total CD4/CD8 ratio was much lower in SCC than in AK and NS,
      which indicates an increase in the CD8+ subpopulation in samples of SCC. In the
      epithelia of SCC samples there were a considerable number of B7/BB1+
      keratinocytes. CONCLUSIONS: We suggest that alterations in the immunodefence
      mechanisms have an important role in the transformation of AK into SCC, and that
      these changes affect not only lymphocytes, but also professional (i.e.,
      Langerhans cells) and non-professional (i.e., keratinocytes) antigen presenting
      cells.

PMID- 9553910
TI  - Comparison of skin atrophy and vasoconstriction due to mometasone furoate,
      methylprednisolone and hydrocortisone.
AB  - BACKGROUND/AIMS: Topical glucocorticoids with improved benefit/risk ratio are of
      great interest in dermatology, but there are very few trials directly comparing
      the efficacy and side-effects of these new preparations. In our study the
      vasoconstrictor effect and side-effects of two of these new glucocorticoids were
      evaluated and blanching effect was determined by two-dimensional laser scanning.
      METHODS: In a randomised, double blind intra-individual comparative trial, 10
      subjects were treated with various glucocorticoids or drug-free vehicle. The test
      drugs were mometasone furoate (MF), methylprednisolone aceponate (MP) and
      hydrocortisone (OH-C). The preparations were tested for a period of 3 weeks with
      occlusion on the flexor side of the forearm. Skin thickness and vasoconstriction
      were determined using 20 MHz ultrasound scanning, laser Doppler scanning (LDS)
      and chromometry. RESULTS: No adverse effects were observed during the observation
      period. Only partial vasoconstriction occurred in most cases during the
      observation period. MP and MF produced maximal blanching between days 3 and 5 of
      treatment, while with OH-C clinically visible blanching did not occur. Ultrasound
      evaluation of skin thickness showed similar behaviour for all three steroids
      tested: there were no signs of skin atrophy in any of the cases. LDS evidenced
      hypoperfusion of a test area on the perfusion image in only a few patients and
      there were no significant differences between the steroids tested. On evaluation
      of vasoconstriction caused by the steroids tested using chromometry there was a
      significant difference between MF and OH-C on the L*a*b* scale (P < 0.005). Only
      at day 3 was a blanching effect caused by MP and MF demonstrable (a-value, P <
      0.05). CONCLUSION: In summary, the synthetic steroids MF and MP presented side
      effects similar to those of OH-C but much greater vasoconstrictor effect; after
      an application period of over 5 days under occlusion a blanching effect in our
      model was not demonstrable by means of chromometry. Two-dimensional laser
      scanning offers no advantage in the evaluation of the blanching effect in
      comparison to one-dimensional laser fluxmetry (LDF).

PMID- 9553909
TI  - Langerhans cells in benign, premalignant and malignant skin lesions of renal
      transplant recipients and the effect of retinoid therapy.
AB  - BACKGROUND AND DESIGN: Langerhans cells (LC) are a unique population of antigen
      presenting cells in the epidermis which may play a role in the defense mechanisms
      against skin tumors. Renal transplant recipients (RTRs) have a significantly
      increased incidence of premalignant and malignant skin lesions. Langerhans cells,
      which are important for local immune surveillance, may be depleted or
      downregulated in skin neoplasms of RTRs, facilitating their growth. We
      investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs),
      five basal cell carcinomas (BCCs), four Bowen's disease, eight dysplastic lesions
      (actinic keratoses), and three viral warts from 15 RTRs and compared these to the
      Langerhans cell densities in normal control skin. Eleven RTRs were receiving low
      dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of
      low-dose retinoid therapy on Langerhans cell densities in SCCs from these
      patients was also assessed. Langerhans cells in frozen tissue sections were
      stained with the anti-human Leu-6 monoclonal antibody. RESULTS: There was no
      significant difference in LC numbers between normal skin from RTRs and normal
      skin from non-immunosuppressed individuals. There was a statistically significant
      reduction in LC/mm2 and LC/1000 K (keratinocytes) for SCC, BCC, dysplastic
      lesions and viral warts compared with normal skin (P < 0.001, P < 0.01, P <
      0.001, P < 0.05, respectively). There was a trend for an increase in Langerhans
      cell density in SCCs which developed during etretinate therapy compared with pre
      etretinate but the difference was not statistically significant. CONCLUSIONS: In
      this study of RTRs, a significant reduction in Langerhans cell densities was
      observed in SCCs, BCCs and dysplastic lesions compared with normal skin. A
      reduction in Langerhans cell density in viral warts from RTRs was also observed.
      A working hypothesis may include a multifactorial etiology for this reduction in
      Langerhans cell densities. It is possible that human papilloma virus (HPV)
      infection, by reducing intraepidermal Langerhans cell density, may decrease local
      immune surveillance and facilitate the development of skin cancers. Ultraviolet
      radiation and immune suppression may also play a role. The marked depletion of
      Langerhans cells in skin cancers, precursor lesions and viral warts suggests a
      central role for Langerhans cells in skin cancer promotion in RTRs.

PMID- 9553911
TI  - Calcipotriol improves the efficacy of cyclosporine in the treatment of psoriasis
      vulgaris.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of
      the association of calcipotriol ointment (50 micrograms/g) plus cyclosporine
      versus cyclosporine alone in the treatment of moderate psoriasis (mean PASI: 13).
      METHODS: Twenty patients were enrolled in this right-left open study. All the
      patients admitted were treated with cylosporine at an initial dose of 4.5
      mg/kg/day; in case of clinical improvement this dosage was reduced by 0.5
      mg/kg/day every 15 days. In each patient we chose two similar, symmetrical
      lesions and calcipotriol ointment was applied only on the right lesion, twice a
      day, until the healing of the lesion or for 1 month. Patients were checked at
      baseline and every 15 days. RESULTS: Eighteen patients completed the study and 17
      of the 18 presented more evident improvement on the side treated with combined
      therapy, while only one patient showed a better result on the side treated with
      cyclosporine alone. A significant difference of the total score was already
      present after 15 days of therapy and was confirmed at the following check-ups.
      CONCLUSIONS: These results underline the usefulness of the association of
      calcipotriol and cyclosporine in order to decrease the total dosage of
      cyclosporine.

PMID- 9553913
TI  - Lichen striatus-like leukoderma.
AB  - A particular pigmentary disorder develops on the skin of Chinese children. The
      lesions are composed of whitish macules and patches arranged in linear bands on
      the extremities unilaterally. Histologically these lesions are hypopigmented
      chronic dermatitis. Although the lesions are arranged in a lichen striatus
      pattern, they differ clinically from lichen striatus by the absence of papules
      and plaques. These cases may represent a new entity. The differential diagnosis
      includes lichen striatus, vitiligo, piebaldism, nevus depigmentosus, and
      hypomelanosis of Ito. The differences between the disorder presented here and
      those of different diagnosis are discussed.

PMID- 9553912
TI  - Plasma concentrations of IFN-gamma and TNF-alpha in psoriatic patients before and
      after local treatment with dithranol ointment.
AB  - IFN-gamma and TNF-alpha plasma levels were measured before and after local
      treatment in 27 patients. Twenty healthy subjects served as controls. Plasma
      concentrations of IFN-gamma and TNF-alpha were significantly higher before
      treatment (178.7 +/- 11.9 pg/ml and 31.9 +/- 11.6 pg/ml, respectively) compared
      to the control group (139.6 +/- 7.86 pg/ml and 17.1 +/- 7.7 pg/ml, respectively).
      After treatment IFN-gamma levels were significantly decreased (151.3 +/- 8.3
      pg/ml) toward the control group values and TNF-alpha levels were observed even
      lower than in the controls (11.48 +/- 6.8 pg/ml). No correlations were found
      between age, duration of psoriasis and plasma levels of cytokines. However, IFN
      gamma levels were related, although not significantly, to disease severity
      (evidenced by the PASI score). The data support the important proinflammatory
      role of IFN-gamma and TNF-alpha in the clinical manifestation of psoriasis.

PMID- 9553915
TI  - Acquired ichthyosis, alopecia and loss of hair pigment associated with
      leiomyosarcoma.
AB  - Acquired ichthyosis is an important clinical finding; internal malignancy,
      systemic disease and medication are recognised associations. We present a 70-year
      old lady with acquired ichthyosis and leiomyosarcoma, one of the less frequently
      associated malignancies. An additional unusual finding was generalised thinning
      and loss of pigment affecting her hair. Scalp biopsy showed histological evidence
      of ichthyosis. Following resection of the tumour the ichthyosis resolved and
      there was regrowth of darker hair.

PMID- 9553914
TI  - Lipodystrophia centrifugalis abdominalis infantilis.
AB  - AIM: To describe the clinical features of lipodystrophia centrifugalis
      abdominalis infantilis (LCAI) with special attention to the erythema which is
      seen around the depressed lesion. BACKGROUND: LCAI is a rare disorder which
      occurs mainly in Asian people, particularly in Japanese; it usually begins as an
      erythematous macule which subsequently expands centrifugally and leaves a central
      depression. However, the erythema has been seldom documented in detail. We here
      report a case of LCAI observed from its early stage and review the literature.
      CASE REPORT: A 2-year-old Japanese girl was brought to our out-patient clinic.
      Clinical examination revealed a slight depression surrounded by faint erythema
      that mimicked morphea on her left inguinum, but there was no hardening of the
      skin. The erythema disappeared 5 months after onset. Thereafter, the
      lipodystrophy expanded irrespective of the treatment to her right inguinum and
      lower abdomen. CONCLUSIONS: The depression continues to grow without the erythema
      in most patients. This suggests that the erythema is not necessary for
      enlargement of the depression although it precedes the depression in most
      patients.

PMID- 9553916
TI  - Childhood cutaneous mucinosis.
AB  - A case of childhood cutaneous mucinosis is described. This is a clinical
      condition that is rarely seen and has only recently been included in the group of
      primary mucinosis.

PMID- 9553917
TI  - Primary cutaneous cryptococcosis in an immune competent patient.
AB  - A 50-year-old female developed a swelling in the epigastrium which later ruptured
      to form a sinus. A diagnosis of primary cutaneous cryptococcosis was made with
      the help of histopathology and microbiological studies. Treatment with
      amphotericin-B and 5-flucytosine gave a good therapeutic response and the sinus
      healed within 2 months.

PMID- 9553918
TI  - Sclerosing sweat duct carcinoma mimicking dermatofibroma.
AB  - Sclerosing sweat duct carcinoma is an infrequent adnexal tumor, locally
      aggressive and with a high incidence of local recurrences. Its location is
      preferably cephalic and its clinical presentation often unspecific. We present a
      new case with an atypical location and the clinical appearance of a benign
      cutaneous lesion. Diagnosis was established after a histological and
      immunohistochemical study. A terminological review was done.

PMID- 9553919
TI  - Familial occurrence of pseudoxanthoma-elasticum-like papillary dermal
      elastolysis.
AB  - We report the morphological, immunohistochemical and ultrastructural cutaneous
      findings of two sisters, aged 72-74, with pseudoxanthoma-elasticum-like papillary
      dermal elastolysis (PDE), recently defined as an age-related condition. To our
      knowledge, these are the first familial cases of PDE reported in the literature.
      The lesions appeared as small, asymptomatic, soft papules around the neck and
      axillary regions. The affected skin revealed a marked decrease of normal elastic
      network of papillary dermis without alterations in either the relevant collagen
      or reticular dermis. Ultrastructural and immunohistochemical examinations showed
      activated dermal fibroblasts with abundant elongated dendritic cytoplasmic
      processes and the absence of myofibroblasts. The well documented avoidance of sun
      exposure (the patients are both nuns), the rare incidence of the disorder (only
      six cases reported), and the familial occurrence suggest that genetic or
      inherited predisposition should also be considered in the pathogenesis of PDE.

PMID- 9553920
TI  - Balneophototherapy in small plaque parapsoriasis--four case reports.
AB  - Four patients suffering from small plaque parapsoriasis were treated successfully
      with balneophototherapy. Within 4 weeks salt-water baths and UV irradiation
      resulted in clinical clearing of more than 90% of lesions with a duration of
      total clinical response between 8 and 12 weeks without further maintenance
      treatment.

PMID- 9553921
TI  - Disseminated histoplasmosis presenting with cutaneous lesions in a patient with
      acquired immunodeficiency syndrome.
AB  - OBJECTIVE: Presentation of a case of disseminated histoplasmosis, observed in a
      non-endemic area, in which cutaneous lesions and fever were the dominant clinical
      signs of the infection. CASE: A 54-year-old homosexual man with acquired
      immunodeficiency syndrome (AIDS) related Kaposi's sarcoma presented with
      cutaneous lesions and fever due to disseminated histoplasmosis. The patient was
      successfully treated with itraconazole 200 mg/day. He died after 8 months from
      AIDS dementia complex: disseminated histoplasmosis relapse was not observed.
      CONCLUSION: The case shows that infection with Histoplasma capsulatum must be
      considered by dermatologists in HIV/AIDS patients, even in non-endemic areas.

PMID- 9553923
TI  - Ulcerative lichen planus-like dermatitis due to long-term hydroxyurea therapy.

PMID- 9553924
TI  - Nail changes in 1000 Indian patients with alopecia areata.

PMID- 9553925
TI  - Effects of cyclosporin A on mycelial transformation of Candida albicans cells in
      human serum.

PMID- 9553922
TI  - An elderly man with vasculitis and IgA myeloma.

PMID- 9553926
TI  - Lichen planus and hepatitis C-virus infection in Turkish patients.

PMID- 9553927
TI  - The effects of various diets on glycogen, protein and lipid levels in the skin of
      albino rats.

PMID- 9553929
TI  - [Diagnosing and treating sinusitis. 8th Congress of the Association for
      Phytotherapy. Symposium: "Phytotherapy in Sinusitis". Wurzburg, 27 November
      1997].

PMID- 9553928
TI  - Congenital angiokeratoma of Fordyce.

PMID- 9553930
TI  - Mechanisms of secretion of toxic organic anions in mammalian kidneys.
AB  - This short review considers the mechanisms of organic anion secretion in renal
      proximal tubules. Particular attention is given to the energy coupling of p
      aminohippurate transport to inorganic anion gradients generated across both
      basolateral and brush-border membranes. The coupling is considered to be a
      consequence of the combined operation of the co-transport and anion-exchange
      mechanisms. A possible coexistence of several organic anion pathways with
      overlapping substrate specificity and/or energetic dependence of the total ion
      gradient are suggested. The problem of identification of transporters involved in
      organic anion secretion is discussed.

PMID- 9553931
TI  - Thermoluminescence in photosynthesis. 4. Influence of energy transfer processes.
AB  - Thermoluminescence (TL) emission arising from charge recombination in
      photosynthetic reaction centres was examined considering the energy transfer
      between antenna chlorophylls and the reaction centre. The energy transfer
      processes were shown to decrease the width and change the temperature of the
      maximum glow of the TL band profiles when the rate constant of direct
      recombination between the oxidized primary electron donor and reduced primary
      acceptor (pheophytin or bacteriopheophytin) did not exceed 10(6) s-1. The primary
      radical pair lifetime of 3.10(-9)-10(-8) s was shown to minimize the influence of
      energy transfer on the TL band profiles and, therefore, the energy transfer can
      be neglected when the TL band profiles are calculated. The profile of the TL band
      arising from charge recombination in the photosystem 2 state S2QB.- was shown to
      depend considerably on the temperature-dependent rate constant of direct
      recombination between QB.- and S2 state of the photosystem 2 donor site.

PMID- 9553932
TI  - Characterization of [3H]AMP binding to rat adipose plasma membranes and its
      substrate specificity.
AB  - We evaluated the binding of [3H]AMP to rat adipose plasma membranes and studied
      the substrate specificity of the process. The [3H]AMP binding was investigated by
      high-speed filtration under conditions of virtually complete inhibition of the 5'
      nucleotidase activity by EDTA/Na. The Scatchard plot revealed the existence of a
      single class of AMP-binding sites on the membrane surface with Kd of 2.14 +/-
      0.210 microM and the binding capacity (Bmax) of 26.0 +/- 0.68 pmol per mg
      protein. Addition of ATP (12.5 microM) or ADP (3.5 microM) to the incubation
      medium resulted in a two-fold increase of Kd, whereas in the presence of
      adenosine (400 microM) or its pharmacological antagonist theophylline (200
      microM), the number of AMP-binding sites decreased. Therefore, ATP and ADP but
      not adenosine compete with AMP for the same nucleotide-binding site. It is
      suggested that the observed [3H]AMP binding may be primarily caused by the
      interaction of AMP with a specific substrate-binding active centre of the
      membrane ectoenzyme 5'-nucleotidase.

PMID- 9553933
TI  - Spatial association of prekinetochores and chromocentres in the interphase nuclei
      of mouse cultured fibroblasts.
AB  - The structure and spatial distribution of prekinetochores and chromocentres
      (centromeric heterochromatin) in the interphase nuclei of mouse fibroblasts were
      studied by light and electron microscopy. Using the autoimmune serum GS reacting
      with centromeric proteins CENP-A, B, C in mammalian cells, we showed that most
      interphase prekinetochores were associated with chromocentres. During the
      interphase S period, including DNA replication in chromocentres, the
      macroorganization of chromocentres and their association with prekinetochores
      were maintained. Using cryosections and the electron microscopy immunogold
      technique, we found that centromeric proteins were mainly located at the
      chromocentre periphery. Nevertheless, we failed to find any definite kinetochore
      structures including those usually observed during mitosis at the sites of
      protein binding. Only small associates of fibrous material, presumably,
      corresponding to centromeric proteins, could be observed in association with the
      interphase mouse chromocentres in both cryosections and conventionally fixed
      sections.

PMID- 9553934
TI  - Phorbol ester at concentrations 10(-18)-10(-7) M inhibits lipid peroxidation in
      rat brain plasma membranes via activation of protein kinase C.
AB  - We studied the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and protein
      kinase C (PKC) in a broad range of concentrations (10(-18)-10(-7) M) on lipid
      peroxidation (LP) in rat brain plasma membranes. TPA and PKC were shown to
      inhibit LP, the concentration curves had two maxima at 10(-15) M and 10(-12) M
      for TPA and at 10(-16) M and 10(-13) M for PKC. The combined action of TPA (10(
      12) M) and PKC (10(-16) M) resulted in a synergic inhibition of LP. These data
      suggest PKC to have two (kinase and antioxidative) enzymatic activities. The
      properties of TPA as an LP inhibitor (via activation of PKC) and tumour promoter
      (inhibition of LP is a necessary step of tumour promotion) can be explained based
      on this suggestion.

PMID- 9553935
TI  - Erythrocyte hemolysis by detergents.
AB  - The numbers of Triton X-100 and sodium dodecyl sulfate molecules required to form
      respective pores were estimated from the relationship between the detergent
      concentrations and the rates of fast and slow hemolysis components. It has been
      found that the slow hemolysis component evoked by Triton X-100 is related to the
      existence of two different pores. It is shown that the fast hemolysis component
      induced by sodium dodecyl sulfate is associated with the modification of
      phosphatidylcholine which determines the break in the Arrhenius plots of the
      hemolysis rate within the range of 20 degrees C. The shape of hemolysis kinetic
      curves and the dependence of hemolytic parameters on the detergent concentration
      and temperature are discussed based on the concept of hemolysis caused by the
      formation of pores in various membrane lipid regions and by releasing vesicles
      from erythrocytes.

PMID- 9553937
TI  - Effective diameters of ion channels formed by homologs of the antibiotic
      chrysospermin.
AB  - Radii of ion channels formed in the lipid bilayer by 4 homologs of the
      alamethicin-like antibiotic, chrysospermin, were determined using hydrophilic
      nonelectrolytes. It is shown that the replacement of isovaline amino acid at
      position 15 of the polypeptide chain by alpha-aminoisobutyric acid results in the
      decrease in the channel effective radius from 1.2 +/- 0.15 to 0.94 +/- 0.1 nm and
      a respective 2.5-fold decrease in channel conductance.

PMID- 9553938
TI  - Redox properties of benzocaine and its homologs.
AB  - Redox properties of the local anesthetic benzocaine and its homologs were studied
      by their reactions with free radical intermediates of dyes excited by the visible
      light. Homologs with more hydrophobic substituents at the benzene ring appeared
      to be better electron donors and facilitated photobleaching of the dye Methylene
      Blue or photoreduction of hemin. The electron-donor properties decreased in the
      same order as their blocking activities (C. Quan, W. M. Mok, and G. K. Wang,
      Biophys. J. 70:194-201 (1996)). This correlation is considered as additional
      evidence in favour of the ion channel redox model.

PMID- 9553936
TI  - Kinetics of tert-butyl hydroperoxide decomposition in erythrocyte suspension.
AB  - The kinetics of tert-butyl hydroperoxide (t-BHP) decomposition was examined in
      erythrocyte suspension from C57B1/6 mice by the chemiluminescence method. The
      reaction with horseradish peroxidase, t-BHP (20 nmol/ml), and luminol was
      accompanied by a rapid chemiluminescence increase. The integral value of the
      chemiluminescence signal correlated with the t-BHP concentration at every moment
      of time. In the erythrocyte suspension, the half-life of t-BHP decomposition was
      23.8 s. The decomposition rate significantly decreased after pretreatment of the
      erythrocytes with o-phenanthroline (0.1 mM), EDTA (1 mM), benzohydroxamic acid
      (0.1 mM) or adriamycin (30 microM). These effects were not associated with the
      changes in the glutathione peroxidase activity and, more likely, could be related
      to the modification of the membrane iron-binding sites. The influence of iron
      chelators on the kinetics of t-BHP decomposition suggests the existence of
      various Fe-binding sites, that can decompose organic hydroperoxides upon their
      interaction with cell plasma membranes.

PMID- 9553940
TI  - The effect of AC voltage on the ionophore-induced steady-state flux across the
      bilayer lipid membrane.
AB  - Application of an AC voltage to a model bilayer lipid membrane in the presence of
      electrogenic ionophores (valinomycin, protonophores CCCP and TTFB) was shown to
      change the steady-state current across the membrane induced by a DC voltage. The
      change in the DC current was proportional to the magnitude of the DC voltage and
      to the amplitude of the AC voltage and depended on both the AC frequency and the
      ionophore used. Application of this new experimental approach to the estimation
      of kinetic constants at individual stages of ionophore functioning is discussed.

PMID- 9553939
TI  - Selective labeling of the inner liposome leaflet by fluorescent lipid probes, and
      studies of liposome fusion with influenza virus.
AB  - The inner leaflet of unilamellar lipid vesicles was labeled with fluorescent
      lysophosphatidylcholines. The probes make a donor-acceptor pair in resonance
      energy transfer (RET), being labeled with 9-anthrylvinyl (L-APC, donor) and 3
      perylenoyl (L-PPC, acceptor) fluorophores. They migrate rapidly between bilayers
      through the water phase: tau 1/2 of equilibration is approximately 5 min at 37
      degrees C. The probe(s) can be removed from the outer leaflet of uniformly
      labeled medium-size unilamellar vesicles (MUV) by repeated washings with excess
      unlabeled large unilamellar vesicles (LUV) (separation by centrifugation). The
      probes flip-flop across bilayers rather slowly. MUV containing the ganglioside
      GT1b and labeled with the L-APC/L-PPC pair in the inner leaflet were fused with
      an equal amount of influenza virus; the process was monitored by an increase of
      the donor fluorescence in RET assay. If inner MUV leaflet was labeled with the
      anthrylvinyl probe only, the probe fluorescence decreased by half when the probe
      was removed from the outer leaflets of the fused membranes. This shows that the
      lipids of the inner and outer leaflets of the MUV randomize in the process of
      fusion.

PMID- 9553941
TI  - Lipid and cell membranes in the presence of gadolinium and other ions with high
      affinity to lipids. 1. Dipole and diffuse components of the boundary potential.
AB  - Two methods were used for monitoring the changes in the boundary and surface
      potentials induced by Gd3+ adsorption--the method of intramembranous field
      compensation applied to planar BLM and electrophoresis of liposomes,
      respectively. The data of both methods agree well in the case of membranes made
      from phosphatidylcholine (PC), in contrast to those made from phosphatidylserine
      (PS). In the latter case, they show a significant discrepancy between potential
      amplitudes even within the micromolar range of Gd3+ concentrations because of
      cation-induced changes in the dipole component of the boundary potential. The
      adsorption of these cations with extremely high affinities to lipids was
      described by the theory of diffuse double layer (Gouy-Chapman-Stern) combined
      with the condition of mass balance, which is essential in the case of limited
      volumes of real systems. The electrokinetic data for PS and PC liposomes are in
      good agreement with the modified theory and correlate well with the Gd3+
      association constants of 5.10(4) and 10(3) M-1, respectively. The same theory was
      used to extract the changes in the dipole component from the measured changes in
      the PS membrane boundary potential. The dependence of this component on the
      number of binding sites occupied by cation was shown to be nonlinear but
      cooperative with the step-like increase of dipole potential up to about 140 mV
      (positive inside the membrane) at the Gd3+ concentration around the zero charge
      point of the PS membranes. This potential corresponds to the structural changes
      in the lipid bilayers which are discussed with respect to the Gd3+ blocking
      effects on the mechanosensitive channels.

PMID- 9553942
TI  - Clinical and genetic aspects of X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (ALD), a leukodystrophy characterized by abnormal
      accumulation of saturated very long chain fatty acids in brain white matter and
      adrenal cortex, is the most common inherited peroxisomal disorder. The
      biochemical defect is localized to the level of lignoceroyl-CoA synthesis, a step
      in the peroxisomal beta-oxidation of very long chain fatty acids. The responsible
      gene encodes a peroxisomal integral membrane protein of as yet unknown function
      which is a member of the ATP-binding cassette transporter protein superfamily.
      The patient gene mutations are heterogeneously distributed over the functional
      protein domains with a tendency to clustering in the nucleotide-binding fold. The
      mechanisms by which these mutations cause a loss of protein function is unknown.
      Diagnosis of patients and carriers, including prenatal testing, is mainly based
      on the clinical picture, the demonstration of increased levels of saturated very
      long chain fatty acids in tissues and body fluids as well as on DNA mutation
      analyses. There are at least six distinct clinical phenotypes ranging from the
      severe childhood cerebral form to asymptomatic persons. The various phenotypes
      commonly occur within the same kindred. Modifying genes and/or environmental
      factors may contribute to this phenomenon. At present, there is no proven therapy
      for the prevention or cure of the neurological disabilities. Several approaches
      are under investigation including diets, immunosuppression, bone marrow
      transplantation and gene therapy.

PMID- 9553943
TI  - 4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde
      dehydrogenase deficiency, an inborn error of GABA metabolism.
AB  - SSADH deficiency, a rare inborn error of human metabolism, disrupts the normal
      metabolism of the inhibitory neurotransmitter GABA. In response to the defect,
      physiologic fluids from patients accumulate GHB, a compound with numerous
      neuromodulatory properties. Clinical and bio-chemical findings in patients are
      contrasted with existing neuropharmacologic data on GHB in animals and men. We
      conclude that GHB contributes to the pathogenesis of SSADH deficiency; whether
      this effect is mediated by GHB, by GABA following metabolic interconversion, or
      via synergistic mechanisms by both compounds, remains to be determined. An animal
      model of SSADH deficiency should further define the role of GHB in the
      pathogenesis of SSADH deficiency, and provide a useful vehicle for the evaluation
      of new therapeutic intervention.

PMID- 9553944
TI  - Guillain-Barre syndrome, case studies and questionnaire to illustrate junior
      doctors' awareness of muscle strength testing.
AB  - Three patients, aged 7-15 years, with Guillain-Barre syndrome presented with pain
      as the primary complaint. Two did not complain of weakness and their progressive
      loss of function was incorrectly ascribed to the pain. One did complain of
      weakness, in association with flu-like symptoms, but the significance of the
      complaint was not appreciated. At diagnosis all three had profound, predominantly
      proximal weakness. We believe the delayed diagnosis relates to doctors' lack of
      opportunity to examine patients with muscle weakness. We conducted a
      questionnaire survey of junior hospital doctors asking them about their hands-on
      experience of testing muscle strength and about their knowledge of the Medical
      Research Council (MRC) Scale of muscle strength. Doctors who claimed most
      experience did not have a better knowledge of the MRC scale. We recommend doctors
      in-training should be given more opportunity to examine patients with muscle
      weakness and should be made familiar with a clinical scale of muscle strength.

PMID- 9553946
TI  - Dramatic effect of ethosuximide on epileptic negative myoclonus: implications for
      the neurophysiological mechanism.
AB  - Epileptic negative myoclonus (ENM) is a recently defined epileptic seizure type
      seen in various epileptic syndromes. Although the long-term prognosis appears to
      be favorable, the treatment of localization-related epilepsy (LRE) with ENM in
      childhood is sometimes difficult due to the apparently pharmaco-resistant nature
      of ENM. We evaluated the effects of antiepileptic drugs (AEDs) in 10 patients
      with ENM. Carbamazepine was administered to eight patients, none of whom
      improved. Responses to clonazepam and valproic acid were unpredictable, whereas
      ethosuximide (ESM) achieved complete control of ENM in all six cases treated with
      this drug as adjunctive therapy. The pharmacological responses of ENM to CBZ and
      ESM were quite similar to those of absence seizures. According to the SPECT and
      ictal EEG findings in addition to the pharmacological responses from this study,
      we favor to postulate that ENM is produced by a direct inhibitory action on the
      motor cortex resulting in the interruption of voluntary muscle contraction as
      generated by sharp-slow wave complexes, compatible with the mechanism considered
      to underlie absence seizures. ENM are refractory to treatment and persisting if
      the wrong AEDs, such as PHT or CBZ, are selected at the diagnosis of LRE. We
      recommended a trial of ESM when ENM develops during the clinical course of LRE
      regardless of etiology.

PMID- 9553947
TI  - Cerebrospinal fluid levels of amino acids in infants and young children with
      chronic renal failure.
AB  - Chronic renal failure (CRF) is associated, especially in young children, with
      delayed cognitive development of unknown origin. As cerebrospinal fluid (CSF)
      reflects the composition of the extracellular fluid of the brain, not only plasma
      but also CSF amino acids concentrations were determined in 8 infants (age 2-8
      months) and 3 children (age 26, 32 and 56 months) with CRF (creatinine clearance
      13 +/- 9 ml/min/ 1.73 m2). In three of these children investigations were
      repeated after six weeks of CAPD treatment. In the infants, a significant
      decrease was found in CSF of alpha-aminobutyric acid, valine, isoleucine,
      leucine, tyrosine, tryptophane, histidine and n-zeta-methyl-1-lysine, whereas
      there was a significant increase of 3-methylhistidine. In plasma serine, valine,
      leucine, tyrosine and histidine were significantly decreased, whereas there was a
      significant increase of aspartic acid, citrulline, and 3-methylhistidine. These
      abnormalities remained constant after the start of CAPD except for the
      normalization in CSF and plasma of 3-methylhistidine. These data indicate a
      generalized disturbance of amino acids in young children with CRF. An abnormal
      substrate is offered to the neurons and astroglia in children with CRF.

PMID- 9553945
TI  - Stopping antiepileptic therapy in mentally-retarded, epileptic children.
AB  - It has, increasingly, become the practice to withdraw antiepileptic drugs (AEDs)
      in epileptic patients, who have been seizure-free for two years. However, the
      presence of mental retardation is frequently considered to be a markedly adverse
      factor for stopping treatment. Many physicians are loth to phase out AEDs in
      mentally retarded patients. In this study, 29 well-controlled epileptic, mentally
      retarded children had their AEDs withdrawn. Seventeen have remained well and 12
      have relapsed. IQ, neurological findings, EEGs, types of epilepsy, frequency of
      attacks, age of onset, duration of the active disease and the fit-free period,
      and antiepileptic drug (AED) levels did not predict the outcome. It is suggested
      that consideration be given to withdrawing AEDs from well-controlled, mentally
      retarded, epileptic children.

PMID- 9553948
TI  - Detection of subclinical central nervous system abnormalities in two patients
      with mucolipidosis III by the use of motor and somatosensory evoked potentials.
AB  - We have studied motor, somatosensory, brainstem auditory and visual evoked
      potentials in two patients with ML III without overt neurologic symptoms. Both
      our patients showed abnormal central motor functions upon magnetic cortical
      stimulation; in addition, in one of them, we observed a decreased conduction
      velocity of the nervous impulse in the central tract of the upper limb
      somatosensory pathway, from the cervical spinal cord to sensory cortex. Our
      results suggest that central motor pathways are affected in both children and
      also that the central somatosensory system is involved in one of them. We propose
      that the electrophysiological techniques might be of help to detect, locate and
      monitor minimal neurological lesions of mild lysosomal disorders like ML III.

PMID- 9553949
TI  - Systemic infantile complex I deficiency with fatal outcome in two brothers.
AB  - A male infant presented at 5 months of age with vomiting, developmental
      stagnation and convulsions. Complex I activity was in skeletal muscle 0.025 mU/mU
      CS (N 0.044-0.265) and in fibroblasts 0.046 mU/mU CS (N 0.100-0.307). Despite
      riboflavine supplementation progressive neurological deterioration occurred and
      he died at 14 months of age. During the mother's following pregnancy complex I
      activity was measured in chorionic villi and found mildly reduced, pregnancy was
      continued. A male infant was born who presented at 7 months of age with vomiting,
      developmental stagnation and hypotonia. Complex I activity was in skeletal muscle
      0.031 mU/mU CS and in fibroblasts 0.100 mU/mU CS. There was progressive
      neurological deterioration and he died at 17 months of age. Complex I activity in
      autopsy liver of both patients was normal. Apparently, complex I deficiency
      presenting in infancy can have a fatal outcome despite only mild reduction of
      enzyme activity in skeletal muscle and/or fibroblasts, and chorionic villi and
      normal activity in liver.

PMID- 9553950
TI  - Reversible palsy of the hypoglossal nerve complicating infectious mononucleosis
      in a young child.
AB  - We report a 7-year-old boy with serologic evidence of active Epstein-Barr virus
      (EBV) infection who developed transient unilateral hypoglossal nerve palsy, with
      complete recovery within 21 days. This is, to our knowledge, the youngest
      reported patient with isolated hypoglossal nerve palsy in the context of EBV
      infection. Acute EBV infection should be considered early in the evaluation of
      children with twelfth nerve palsy in order to avoid extensive ancillary testing.

PMID- 9553951
TI  - Infantile muscle phosphorylase-b-kinase deficiency. A case report.
AB  - A Turkish girl is described who showed a severe floppy infant syndrome and
      respiratory failure at birth. She suffered upper respiratory tract infections and
      pneumonia. She was ventilated and had hypercapnoea secondary to bradypnoea.
      Biochemical analysis of skeletal muscle revealed a slightly increased glycogen
      content, and enzymatic analysis revealed a muscle phosphorylase-b-kinase
      deficiency. The infant succumbed after 140 days due to persistent apnoea and
      asystole. Isolated muscle phosphorylase-b-kinase deficiency should be considered
      as a possible diagnosis in floppy infants.

PMID- 9553953
TI  - 3-Methyl glutaconic aciduria in Iraqi Jewish children may be misdiagnosed as
      cerebral palsy.
AB  - It is generally accepted that patients with cerebral palsy suffer from a static
      encephalopathy causing a non-progressive disorder of posture and/or movement. We
      describe 7 patients from 5 families who were initially diagnosed with cerebral
      palsy. Eventually, excessive excretion of urinary 3-methyl glutaconic acid (3
      MGA) was found. The data of our 7 patients are quite similar to the clinical
      description of Costeff et al (1989): Jewish-Iraqi origin (7/7), consanguinity
      (2/7), involuntary movements (5/7), ataxia (6/7), pyramidal involvement (6/7) and
      optic atrophy (6/7). The cognitive functions were intact in 5/7 and 2/7 showed
      mild to moderate mental retardation. The mean delay in the definitive diagnosis
      was 9 years. Cerebral palsy-like symptoms accompanied by optic atrophy and
      extrapyramidal signs should call for extensive metabolic evaluation including the
      determination of urinary 3-MGA.

PMID- 9553952
TI  - Adenylosuccinase deficiency with neonatal onset severe epileptic seizures and
      sudden death.
AB  - We report a male infant with adenylosuccinase deficiency who developed epileptic
      seizures on the second day of life. Growth was normal and seizures were well
      controlled with anti-epileptic drugs. Despite axial hypotonia associated with
      peripheral hypertonicity he presented some development until seven months of age,
      when he developed high fever and died within a few hours. Although clinical
      heterogeneity in this disorder of purine synthesis and interconversion is well
      known, in 14 out of 17 cases who experienced epilepsy seizures started after the
      first year of life. The early presentation in our index patient followed by his
      sudden death at the age of 7 months has not been described before. A search for
      disorders of purine metabolism should be included in the screening programme for
      every child with severe neonatal convulsions.

PMID- 9553955
TI  - Blood mercury and auditory neuro-sensory responses in children and adults in the
      Nambija gold mining area of Ecuador.
AB  - This study investigated blood mercury (B-Hg) levels and the auditory neuro
      sensory status of children and adults in the remote Andean settlement of Nambija,
      Ecuador where Hg is used in the extensive gold mining operations. The mean B-Hg
      level in 75 Nambija (Study Area) inhabitants (36 children and 39 adults) was 17.5
      micrograms/L (SD = 11.0) vs 3.0 micrograms/L (SD = 1.6) in a second group of 34
      subjects (15 children and 19 adults) in a non-gold mining area (Reference Area),
      the difference being statistically significant (p < 0.0001). Neuro-otological
      examinations revealed 34 subjects (45%) with complaints of headaches and/or
      memory loss, 3 cases of severe neurological impairment and 4 cases of middle ear
      pathology. Audiological tests on 40 persons in the Study Area (21 children and 19
      adults) showed hearing thresholds ranging from normal to mildly abnormal at 2, 3,
      4, 6 and 8 kHz for children, and normal to severely abnormal for adults.
      Correlation coefficients showed a significant relationship between B-Hg level and
      hearing level in children at 3 kHz in the right ear, and at no frequency for
      adults. Auditory brainstem evoked responses (ABR) on subjects in the Study Area
      showed a significant correlation between B-Hg and the I-III interpeak latency on
      the right side. The results indicated that the study population of the Nambija
      gold mining area had abnormally elevated B-Hg levels, and may be at neurological
      risk from exposure to methylmercury (MeHg) from the consumption of contaminated
      food and possibly from elemental Hg vapors inhaled during amalgam burning in the
      gold extraction process.

PMID- 9553954
TI  - Interaction of phentermine plus fenfluramine: neurochemical and neurotoxic
      effects.
AB  - Previous studies have reported the use of combined serotonergic and dopaminergic
      agonists in the treatment of obesity and alcoholism. Along these lines,
      phentermine plus fenfluramine has been suggested as a possible clinical treatment
      for alcohol craving. To determine the neurochemical effects of a combined
      treatment of phentermine plus fenfluramine, animals were injected subcutaneously
      with saline, phentermine 12 mg/kg, fenfluramine 16 mg/kg, or a combination of
      phentermine plus fenfluramine. One hour after injection, animals were sacrificed
      and neurochemical analysis performed. Furthermore, separate groups of animals
      were given the same injections 8 times, 12 hours apart, to determine the effects
      on body weight and to detect a possible exacerbation of fenfluramine induced
      toxicity. The drug combination produced a significant rise in dopamine in the
      striatum, greater than that seen with either drug alone. Furthermore, the
      addition of phentermine reduced the fenfluramine induced rise in striatal 3,4
      dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindolacetic acid (5
      HIAA). Phentermine plus fenfluramine combination produced a greater weight loss
      than either drug alone, however, it did not produce a significantly greater drop
      in striatal serotonin or 5-HIAA levels above that induced by fenfluramine alone.
      Thus, while previous studies report the potentiated neurotoxicity of phentermine
      plus fenfluramine over fenfluramine alone, the present study does not indicate
      that such an effect occurs following an administration regimen analogous to that
      of patients treated with the drug combination.

PMID- 9553956
TI  - Regional distribution of 203PbCl2 in the mouse after intravenous injection.
AB  - Lead is a known neurotoxicant, and concentrations of lead in the CNS after acute
      exposure to low doses have not been studied in detail. In this investigation, the
      temporal distribution of lead ([203Pb]), injected intravenously at no-carrier
      added (NCA) (0.6-0.7 mumol/kg) and at carrier-added (7.0-62.3 mumol/kg) levels
      was determined in mice. Concentrations of [203Pb] were measured in major organs
      and in different regions of the brain. Ex-vivo autoradiographic visualization was
      used to confirm and extend the brain distribution findings. RESULTS: The highest
      concentrations of NCA [203Pb] were observed initially in the kidneys (52% of the
      injected dose (ID)/g at 1 hr) and liver (10.5% ID/g at 30 min). Uptake into bone
      occurred gradually, reaching 25% ID/g at 24 hr. In accord with previous reports,
      excretion of the tracer was very slow. Approximately 80% of total ID remained in
      the body after 24 hr and 68% at 48 hr. Interestingly, in the mouse brain, the
      highest levels of [203Pb] were noted in the area of the hypothalamus. At all
      times between 30 min and 16 hr postinjection, and at all Pb dose levels injected,
      the accumulation of [203Pb] in the hypothalamic region exceeded that in all other
      brain regions examined. Autoradiography performed at the 16 hr time point
      confirmed the high uptake and strong retention of [203Pb] by the hypothalamus.
      These studies afford new insight into the distribution of acutely administered
      lead in the brain, and may have implications for the understanding of some of the
      neurotoxic effects of lead.

PMID- 9553957
TI  - Reversal by desferrioxamine of tau protein aggregates following two days of
      treatment in aluminum-induced neurofibrillary degeneration in rabbit:
      implications for clinical trials in Alzheimer's disease.
AB  - A clinical trial in patients with Alzheimer's disease has indicated that frequent
      intramuscular (i.m.) treatment with desferrioxamine (DFO) slows progression of
      the disease. Confirmatory trials have not been carried out, partly because of the
      rigors of twice daily intramuscular injections over a period of 2 years, even
      though the initial report gave promising results. The aim of the present study
      was to determine an optimal DFO treatment protocol in an animal model exhibiting
      Alzheimer's-like intraneuronal protein aggregates, previously shown to be
      partially reversed by such treatment. New Zealand white rabbits were injected
      intracisternally with either aluminum (Al) maltolate or with saline on day 0.
      Intramuscular injections of DFO were given to selected rabbits for 2 days prior
      to sacrifice on days 4, 6 or 8. Bielschowsky's silver impregnation demonstrated
      widespread neurofibrillary degeneration (NFD) in neuronal cell bodies and
      neurites of brain and spinal cord from Al-treated rabbits. Monoclonal antibodies
      Tau-2, AT8, PHF-1 and Alz-50, all of which characteristically stain
      neurofibrillary tangles associated with Alzheimer's disease, strongly labeled the
      Al-induced NFD. The number of positive neurons and staining intensities were much
      less in rabbits treated with Al and subsequently with DFO, than in animals only
      given Al. Control rabbit receiving intracisternal saline were negative for NFD.
      The results of quantitative immunohistochemistry using image analysis confirmed
      that immunostaining densities with all tau mAbs were higher in Al-treated than in
      Al-DFO-treated or in saline-treated controls. Furthermore, it appears that
      hyperphosphorylation of tau does not make this protein resistant to degradation
      once Al has been removed by DFO treatment. The effectiveness of only two days of
      DFO treatment in reversing Al-induced neurofibrillary degeneration suggests that
      further clinical trials of DFO for treatment of Alzheimer's disease should be
      attempted using much less frequent administration of DFO than in the initial
      study (Crapper McLachlan et al., 1991).

PMID- 9553958
TI  - Trimethylolpropane phosphate (TMPP) perfusion into the nucleus accumbens of the
      rat: electroencephalographic, behavioral and neurochemical correlates.
AB  - The infusion (0.13 mumol/infusion) of the convulsant trimethylolpropane phosphate
      (TMPP) into the nucleus accumbens (NA) of adults Sprague-Dawley rats reliably
      induced subclinical seizures, hyperlocomotor activity, and integrated
      stereotypies. Observation of these behaviors was temporally correlated with the
      appearance of EEG paroxysms, as well as with significant decreases in
      extracellular concentrations of both dopamine (DA) and norepinephrine (NE) in the
      NA. Repeated perfusion of TMPP revealed significant increases in stereotypic
      behavior during subsequent pre-drug baseline testing.

PMID- 9553959
TI  - Acidosis-induced metallothionein (MT) mRNA expression in neonatal rat primary
      astrocyte cultures.
AB  - Metallothionein (MT) mRNA levels were determined following exposure of neonatal
      rat primary astrocyte cultures to acidosis. Astrocyte total RNA was probed on
      northern blots with [alpha 32 P]dCTP-labeled synthetic cDNA probes specific for
      rat MT isoform mRNAs. The probe for MT-I mRNA hybridized to a single mRNA with a
      size appropriate for MT, approximately 550 nucleotides. MT-I mRNA levels in
      astrocyte monolayers exposed to pH 6.5 and 6.0 for 3 or 6 hours were unchanged
      compared with MT-I mRNA levels in control cultures exposed to pH 7.4. In
      contrast, 9 hour exposure of astrocytes to pH 6.5 and 6.0 led to a significant
      increase in MT-I mRNA transcripts compared with controls maintained at pH 7.4 (p
      < 0.001 and p < 0.02, respectively). A probe for MT-II mRNA that hybridizes to a
      single mRNA (450 nucleotides) was also used to determine the effect of acidosis
      on astrocyte MT-II mRNA transcripts. Although statistical significance was not
      attained, a similar trend was noted, with a 9 hour exposure to pH of 6.5 and 6.0
      resulting in increased astrocytic expression MT-II mRNA compared with control
      cells maintained at pH 7.4. Acidosis was also associated with a pH-dependent
      increase in astrocytic volume. Accordingly, acidosis is invoked as an added
      stimulus to stress factors associated with the induction of astrocytic MT mRNA
      transcripts.

PMID- 9553960
TI  - Prosaptide prevents paclitaxel neurotoxicity.
AB  - Paclitaxel (Taxol), a chemotherapeutic agent used to treat breast and ovarian
      tumors, has been reported to induce a predominantly sensory neuropathy. Co
      treatment with neurotrophic factors and paclitaxel has been proposed for
      preventing or reversing paclitaxel-induced peripheral neuropathy. Prosaposin, the
      precursor of saposins A, B, C and D was recently identified as a neurotrophic
      factor and was reported to facilitate nerve regeneration in vivo. Peptides
      (prosaptides) encompassing the neurotrophic sequence located in the saposin C
      domain, have neurotrophic activity similar to the holoprotein (O'Brien et al.
      1995). In the present study, we investigated the effect of a 14-mer prosaptide,
      TX14(A), or a 22-mer prosaptide, 769P, on paclitaxel-induced neutrotoxicity in
      vitro and in vivo. Paclitaxel treatment (1 microM) decreased cell viability of
      both PC12 and Schwann cells. TX14(A) (10 nM) prevented paclitaxel-induced loss of
      cell viability in PC12 cells but not in Schwann cells. Systemic injections (i.p.)
      of paclitaxel (1.2 mg/kg/day) given five times per week for three weeks
      (cumulative dose 18 mg/kg) or given every third day (25, 12.5 and 12.5 mg/kg) for
      10 ten days (cumulative dose 50 mg/kg) in adult rats induced thermal hypoalgesia
      that was not accompanied by morphological changes in the sciatic nerve or changes
      of nerve conduction velocity. Co-administration of paclitaxel with prosaptides
      (cumulative dose 3 or 10 mg/kg) prevented paclitaxel-induced thermal hypoalgesia.
      In the short-term high dose study, paclitaxel treated rats lost 10% of their body
      weight, had reduced erythrocyte counts, hematocrit and hemoglobin concentrations
      which were not prevented by treatment with prosaptide. TX14(A) did not diminish
      paclitaxel cytotoxicity of breast cancer cells in vitro. These findings suggest
      that prosaptide prevents the neurotoxic effects of paclitaxel while not
      interfering with its anti-tumor activity.

PMID- 9553961
TI  - Block of neuronal voltage-dependent K+ channels by diacylhydrazine insecticides.
AB  - RH-5849 (1,2-dibenzoyl-1-tert-butylhydrazine), a novel insect growth regulator,
      also produces acute neurotoxic symptoms by selectively blocking the maintained
      voltage-dependent K+ current (IK) in nerve and muscle Salgado (1992). The effects
      of RH-5849 and an analog were examined on IK channels in internally-perfused
      crayfish giant axons. For bilaterally applied RH-5849, the concentration needed
      for 50% block (IC50) was 79 +/- 6 microM (mean +/- SEM, n = 3), with a Hill
      coefficient near 2. Block was independent of membrane potential, but dependent on
      time, with a speed proportional to concentration, suggesting an open channel
      block mechanism. In addition to their effects on IK, both diacylhydrazines were
      much weaker blockers of the voltage-dependent sodium current (INa). RH-5849
      blocked IK from either side of the membrane, and was more potent when applied
      bilaterally. When RH-5849 was introduced inside the axon and internal perfusion
      was halted, IK increased within a few minutes to the control level, indicating
      that the compound diffused freely through the membrane and bound to a receptor
      within the plane of the membrane. The permeability coefficients measured in the
      stopped-flow experiments indicate that diacylhydrazines can diffuse readily
      throughout the body of a poisoned insect, consistent with the rapid onset of
      central nervous system symptoms following injection. The octanol:water partition
      coefficient of RH-5849 increased sharply from 145 to 258 at aqueous
      concentrations between 5 and 10 microM, suggesting that a new phase, possibly
      micellar, is formed in the octanol phase. This may be responsible for the
      anomalously high Hill coefficients for the channel blocking activity of the
      diacylhydrazines.

PMID- 9553962
TI  - Chemical sensitivity and the immune system: a paradigm to approach potential
      immune involvement.
AB  - This paper approaches the issue of chemical sensitivity and the immune system
      though a consideration of established environmentally-induced immune alterations
      which have particular relevance to the broader topic of chemical sensitivity.
      Additionally, the report discusses the potential problems associated with prior
      narrow evaluation strategies for the assessment of environmentally-induced
      inflammation. A combined approach to assessment drawing upon biomarkers of both
      the immune and neurological systems is suggested. Such an approach recognizes the
      key roles which mediators of these two systems play in facilitating host
      inflammatory responses. The paper concludes with a discussion of the types of
      specific immune alterations which, from a mechanistic perspective, are likely to
      be involved with any linkage of chemical sensitivity to the immune system.

PMID- 9553963
TI  - Neurobehavioral properties of chemical sensitivity syndromes.
AB  - Chemical sensitivity Syndromes refers to aggregations of symptoms marked by
      largely subjective neurobehavioral complaints and hypothesized links to immune
      system dysfunction. The entities reviewed here consist of the Multiple Chemical
      Sensitivity Syndrome, the Sick Building Syndrome, the Chronic Fatigue Syndrome,
      and the Gulf War Syndrome. Except for the Chronic Fatigue Syndrome, toxic
      chemical exposures are accorded a significant role in their etiology. The
      connections are ambiguous because of the variety of chemical agents cited and,
      for the most part, the relatively low levels at which exposures occur.
      Conventional clinical signs are also typically lacking. Explanatory mechanisms
      include psychiatric diagnoses such as somatization, behavioral mechanisms such as
      conditioning and generalization, neuropharmacological mechanisms such as
      sensitization, and psychoneuroimmunological mechanisms such as those involving
      the hypothalamic-pituitary-adrenal axis. Laboratory animal experimentation and
      controlled clinical trials, especially with inhaled material, provide the means
      for exploring the proffered explanations.

PMID- 9553964
TI  - Astrocytes as mediators of immune and inflammatory responses in the CNS.
AB  - The long-standing view that the brain is isolated from the effects of the immune
      system has recently been challenged, with experimental evidence suggesting that
      in response to invasion by microorganisms, the CNS can mount its own defense by
      resident cells, such as the microglia and astrocytes. Both cell types produce and
      secrete a number of cytokines and therefore can potentially modulate and
      integrate the communication between hematogenous cells and resident cells of the
      CNS. This manuscript will commence with a brief overview of astrocytic functions
      in the CNS, and proceed to discuss astrocytic responses that may regulate CNS
      inflammation. Specifically, it will address (1) the function of astrocytes as the
      antigen presenting cells (APCs) of the CNS, and (2) the role afforded by
      astrocyte-derived cytokines, and astrocytic responses to cytokines secreted
      elsewhere, in mediating and sustaining immune responses. Finally, some recent
      experimental evidence on the possibility that astroglial impairment by pathogens
      may contribute to the etiology of neurologic diseases will be highlighted.

PMID- 9553965
TI  - Lead potentiates cytokine- and glutamate-mediated increases in permeability of
      the blood-brain barrier.
AB  - We have measured the transendothelial electrical resistance across the blood
      brain barrier (BBB) with a microelectrode technique and determined the effects of
      subcutaneous injections (five injections over ten days) of lipopolysaccharide
      (LPS, 100 ng/g), recombinant mouse interleukin-6 (IL-6, 5 ng/g), and/or inorganic
      lead (lead, 2.5 5 micrograms/g) on the ion permeability of arterioles in the
      temporoparietal cortex of anaesthetized mice between 10 and 40 days of age. In
      controls the electrical resistance increased with age. It was decreased in
      animals treated with IL-6, but unaffected by lead at the different ages studied.
      In IL-6 treated mice, repeated neonatal exposure to lead (five injections between
      2 and 10 days after birth) caused a delay in the increase in arteriole resistance
      with age. LPS injections caused a 36% increase in ion permeability of the BBB in
      twenty-day-old mice, and lead potentiated this effect of LPS. Intra-arterial
      injections of glutamate did not alter vascular resistance, but topical
      applications of glutamate on the cerebrum caused a reversible decrease in the
      resistance in mice not treated with lead, and an irreversible decrease in mice
      treated with lead. Injections of glutamate in the lumen of arterial vessels in
      the parietal and temporoparietal brain areas of mice pretreated with lead and
      LPS, plus a topical application of glutamate, caused depolarization of neurons in
      the temporoparietal cortex. These results suggest that disruption of the BBB can
      allow serum glutamate to penetrate the brain, causing further disruption of the
      BBB, and that lead irreversibly potentiates this cascade of harmful events.

PMID- 9553968
TI  - A review of methylmercury and child development.
AB  - Methylmercury (MeHg) is a neurotoxin present in both fresh and saltwater fish
      throughout the world. Increased levels of MeHg can be found in individuals who
      regularly consume fish. The developing brain is very sensitive to the deleterious
      effects of MeHg, and prenatal exposure can occur when the mother has a diet high
      in fish. If the level of MeHg exposure achieved by eating fish adversely affects
      the fetus or child's neurological development it could have far reaching public
      health implications. Studies of human prenatal MeHg poisoning in Iraq suggest
      that MeHg levels achieved by eating fish may affect neurological development even
      when the fish MeHg levels are not elevated by obvious pollution. Studies in fish
      eating populations have identified adverse neurological and developmental
      outcomes, but these findings have not been consistent. Additional studies are
      presently underway to determine whether consistent adverse outcomes can be
      identified using more sensitive testing methods and examining children older than
      in previous studies. This review examines studies of human prenatal and postnatal
      MeHg exposure. Studies of poisoning episodes where children are symptomatic and
      studies of fish eating populations where no symptoms are apparent will be
      addressed. Individuals around the world depend on fish as a protein source and
      increasing evidence suggests that regular fish consumption has cardiovascular
      benefits. It is not presently clear whether MeHg exposures from a high fish diet
      adversely affect children's neurological development, but it is an important
      question to answer.

PMID- 9553966
TI  - Lipopolysaccharide and interleukin-6 enhance lead entry into cerebellar neurons:
      application of a new and sensitive flow cytometric technique to measure
      intracellular lead and calcium concentrations.
AB  - The distribution of intracellular ionized lead (Pb) and calcium in dissociated
      cerebellar cells of ten-day-old mice was measured by flow cytometry. There are no
      fluorescent probes specific for lead, whereas commonly used fluorescent calcium
      indicators bind heavy metals with greater affinity than they do calcium, which
      impedes discrimination of lead- and calcium-induced fluorescence changes.
      Therefore, we developed a method to determine [Pb2+]i and [Ca2+]i by employing a
      combination of the calcium indicator fluo-3 and the heavy-metal chelator TPEN.
      Using these methods, we studied the effects of multiple in vivo exposure (five
      subcutaneous injections over 10 days) to lipopolysaccharide (LPS, 100 ng/g),
      recombinant mouse interleukin-6 (IL-6, 5 ng/g) and/or inorganic lead (lead, 2.5
      micrograms/g) on lead and calcium concentrations. Control cells had [Cai] of 112
      nM. Lead exposure alone had little effect on [Ca2+]i and resulted in a mean
      [Pb2+]i of about 7 pM, and did not alter cell volume. A significant fraction of
      cells (about 44% of living cells) from animals treated with lead plus LPS were
      swollen, as determined by analysis of the light scattering pattern, and there was
      a small increase in the number of dead cells, identified with the nucleic acid
      stain, 7-aminoactinomycin. While [Ca2+]i was not significantly increased in
      animals treated with either only LPS or IL-6, lead and calcium concentrations
      were increased in animals exposed to lead and LPS or IL-6 in both the non-swollen
      and swollen cells, with a mean value of (Pb2+)i of 32 pM and (Ca2+)i of 155 nM in
      cells not swollen. Electrophysiological analysis showed that LPS injections
      caused decreases in the membrane potential of endothelial cells of the blood
      brain barrier (BBB) and lead potentiated the effect of LPS. IL-6 mimicked the
      effects of LPS, but was less potent. Thus these experiments indicate a
      synergistic interaction between lead and cytokines on biophysical properties of
      both neurons and endothelial cells of the BBB.

PMID- 9553967
TI  - Developmental neurotoxicity and immunotoxicity of 2,4,6-tribromophenol in Wistar
      rats.
AB  - Pregnant Wistar rats were exposed to 2,4,6-Tribromophenol (TBP) by whole body
      inhalation (0, 0.03, 0.1, 0.3, 1.0 mg/m3, 24 hr/day, 7 days/weeks, from day 1 to
      21 of gestation). Significant decreases in orientation reactions were noted at
      concentrations of 1.0 mg/m3 (p < 0.05) in the open field test. Nonsignificant
      trends (p > 0.05) toward decreased horizontal movement and emotionality in the
      open field and increased electrical impulse skin pain threshold (SPT) were
      observed. No significant exposure-related differences in the nonspecific
      immunological status (phagocytosis and blood anti-microbe activity) of pregnant
      rats were seen after the exposure. Preimplantation and postimplantation embryo
      losses were significantly increased in a dose-dependent manner and were seen in
      all treated groups except the lowest concentration (0.03 mg/m3) group. Signs of
      retarded fetal skeletal development and increased frequencies of visceral
      abnormalities were found at concentrations of 0.1 and 1.0 mg/m3. Significant
      effects were found for lower incisor eruption and ear unfolding at a
      concentration of 0.3 mg/m3. The grooming behavior of 30-day old male progeny was
      significantly less than control in all experimental groups. Grooming behavior in
      female subjects exposed to a concentration of 0.3 mg/m3 and emotionality in
      subjects exposed to a concentration of 1 mg/m3 were decreased significantly. At
      60 days of age emotional reactions were significantly decreased in female
      subjects from the 0.03, 0.3 and 1.0 mg/m3 groups. SPT was significantly increased
      in the 1 mg/m3 group for both male and female pups. Thus, evidence of CNS
      depression influence of TBP both in maternal and offspring groups was found. The
      NOEL (No Observed Effect Level) for developmental neurotoxicity is thus < 0.03
      mg/m3, and the NOEL for maternal neurotoxicity is 0.3 mg/m3. These results
      suggest that exposure to TBP for 24 hr/day throughout gestation may cause
      developmental neurotoxicity, embryotoxicity and fetotoxicity, but not
      immunotoxicity.

PMID- 9553969
TI  - A method for the induction of a cochlea-specific auditory deprivation in the
      gerbil (Meriones unguiculatus).
AB  - The neurophysiological effects of early electrical stimulation on the development
      and neural plasticity of the central auditory system in prelingually deafened
      children with cochlear implants are still unknown. Many of these basic questions
      can be answered systematically only in animal experiments. Meriones unguiculatus
      is a well-established animal model in hearing research. Deafening is produced by
      a single intracochlear application of an ototoxic aminoglycoside antibiotic
      (neomycin sulfate) on the 14th day after birth (DAB), i.e. before the late
      natural onset of hearing on the 16th DAB. A single application of the antibiotic
      abolishes auditory brainstem responses (ABR) to clicks completely and reduces
      sensitivity to low frequency tonebursts by 50 dB SPL. Scanning electron
      microscopy results show a destruction of the stereocilia of the inner and outer
      hair cells of the basal and medial cochlear turn and a reduction of those in the
      apical turn. Our method avoids a systemic application of antibiotics and can be
      used in studies dealing with the consequences of different forms of auditory
      deprivation, neuronal compensation processes or with ontogenetic studies and
      chronic electrostimulation in an animal model.

PMID- 9553970
TI  - Localization of nitric oxide synthase isoforms (NOS I, II and III) in the
      vestibular end organs of the guinea pig.
AB  - The localization of nitric oxide (NO) synthase (NOS) isoforms was investigated in
      the vestibular organ of the pigmented guinea pig by indirect
      immunohistochemistry. The cytoplasm of both type I and type II vestibular sensory
      cells as well as vestibular ganglion cells showed both NOS I and III
      immunoreactivity, whereas there was no reactivity in their nuclei and sensory
      hairs. The afferent nerve chalices were usually not stained. NOS III staining was
      also observed in the nerve fibers contacting type II cells and in the
      subepithelial tissue. The endothelial lining of the blood vessels displayed
      reactivity for NOS III. The cytoplasm of fluid transporting cells showed weak
      staining for NOS I and moderate staining for NOS III. Immunostaining for NOS II
      did not display any reactivity in general. These findings may suggest that NO is
      a mediator of neurotransmission in the vestibular system in sensory cells and
      ganglia. NO in the fluid transporting cells may play an important role for
      maintaining the endolymph and ion homeostasis, and NOS III in vascular
      endothelial cells implies regulatory effects of NO on vascular wall tonus and
      vestibular blood supply.

PMID- 9553971
TI  - Calcium mobilization in isolated epithelial cells of the endolymphatic sac.
AB  - Endolymphatic sac epithelial cells were isolated from the endolymphatic sac of
      the guinea pig by enzymatic and mechanical dissociation. The intracellular free
      calcium ion concentrations ([Ca2+]i) of the isolated cells were determined using
      the Ca(2+)-sensitive dye fura-2. The isolated cells were classified into two
      types, i.e. light and dark cells. In the resting state, [Ca2+]i in the cells was
      variable in both types of cells. In the presence of 200 microM ATP, there was a
      rapid rise in [Ca2+]i. These findings suggest that endolymphatic sac epithelial
      cells may have receptor-mediated Ca channels which may play an important role for
      a nerve-mediated local feedback system of the endolymphatic sac to regulate
      homeostasis of endolymph volume, pressure and electrolyte balance.

PMID- 9553972
TI  - Vascular inner ear partition: a concept for some forms of sensorineural hearing
      loss and vertigo.
AB  - The results of a series of scanning electron microscopical studies were used to
      construct a model for the vascular pathways in the inner ear. Corrosion cast
      preparations of the vessels of the inner ear of the adult rat were used in this
      study. The inner ear is, like a hand, an end organ containing four sense organs
      (cochlea, saccule, utricle and the cristae ampullaris). All these specific inner
      ear structures have their own vascular supply. We have developed a blood flow
      diagram of the inner ear. This model was used for a classification of different
      types of ischemia in the inner ear and forms a concept for some forms of
      sensorineural hearing loss and vertigo. Four types of inner ear ischemia are
      proposed. In type I (a or b) of inner ear ischemia only the vessels of the
      cochlea are involved resulting in two types of hearing loss without vertigo. Type
      II is characterized by ischemia of a part of the cochlea and a part of the
      vestibular system. In type III (a or b) only the vestibular system is involved,
      while in type IV no blood circulation will be present in the inner ear resulting
      in total deafness and severe vertigo. Inner ear partition at ultramicroscopical
      level of these structures may be possible in the future and new imaging
      techniques will probably support the vascular schematic model presented in this
      study.

PMID- 9553973
TI  - Vestibular function and cochlear implant.
AB  - The authors illustrate their personal experience relating to 32 patients, aged
      between 12 and 74 years, undergoing cochlear implant, in whom vestibular reflexes
      were evaluated before and after surgery. This series did not include cases of
      areflexia, but only 1 case of reduced vestibular reflexia consequently to
      surgery. In this case, owing to the probable intervention of central compensation
      processes, labyrinthine hyporeflexia never became clinically significant. These
      personal results enable the authors to affirm that preoperative vestibular
      reflexes do not offer elements able to influence the choice of the ear in which
      to perform the cochlear implant. In the series of patients reported by the
      authors, a cochleostomy by removal of the floor of the round window niche,
      following the suggestions of O'Leary et al., always headed the electrode implant.
      This contrivance may reduce or eliminate the negative effects on vestibular
      receptors indirectly caused by the consequent and inevitable alteration of
      perilymph pressure produced by the implant.

PMID- 9553974
TI  - The effect of ammonia on olfactory epithelium and vomeronasal organ
      neuroepithelium of rabbits. A histological and histochemical study.
AB  - In recent studies, the vomeronasal organ (VNO), although vestigial and with
      unknown function in humans, was reported to be present in almost every person
      examined. In rabbits, it is a well-developed organ, one lying on each side of the
      nasal septum. Histologically it was found to contain neuroepithelium which is
      considered an accessory olfactory system taking charge of an olfactory
      discrimination different from that of olfactory epithelium. Experimental removal
      of the VNO in male animals reduces reproductive performance and aggression. In
      this study, the effects of prolonged exposure to ammonia vapor on the
      histological pattern and enzymatic activity of the olfactory epithelium and the
      VNO neuroepithelium of 30 adult male rabbits were investigated and compared with
      a control group. In the exposed animals, the supporting cells in both types of
      epithelia showed hyperplasia which was more marked in the olfactory epithelium.
      Manifestations of cytotoxicity were found more in the bipolar cells of the
      olfactory epithelium than in the VNO neuroepithelium. The enzymatic activity in
      the exposed group supported the histological results. The presence of the VNO
      neuroepithelium of the rabbit in a narrow duct with a minute nasal orifice could
      have some protective effects on the cells.

PMID- 9553975
TI  - Clinical-morphological correlation of nasal obstruction with skull base
      development and otitis media. An experimental study.
AB  - Morphological changes of the middle ear were investigated by means of
      microotoscopy and scanning electron microscopy in 40 developing Albino rats. In
      20 one nostril (group B) and in 20 both nostrils (group C) had been
      experimentally obstructed. 20 rats were used as controls (group A). Microotoscopy
      and scanning electron microscopy on the middle ear mucosa were performed when the
      animals were 2 months old, i.e. at 90% of their development. At microotoscopy the
      tympanic membranes, homolateral to the obstructed nostril, proved to be abnormal
      in 81% of group B rats and in almost all rats belonging to group C. Scanning
      electron microscopy, performed after the bullae had been removed, showed the
      following epithelial surface changes of the middle ear homolaterally to the
      obstructed nostril: (a) a significant increase of nonciliated elements with a
      secretory behavior as compared to controls, even of the floor where normally a
      large number of ciliated cells is present; (b) several ciliated cells were
      destroyed and their cilia were irregular and untidy; (c) thick mucous secretions
      covered the floor of the tympanic bulla; and (d) squamous metaplasia of the
      hypotympanic epithelium. Extrarotation of the eustachian tubes and developmental
      abnormalities of the skull base in growing rats, caused by nasal obstruction,
      seem to be able to induce pathological events of the middle ear.

PMID- 9553976
TI  - Effects of isoproterenol on the orbicularis oculi and stapedius muscles.
AB  - The effect of the beta-adrenoceptor agonist, isoproterenol, on the orbicularis
      oculi and stapedius muscles was studied. Rats were injected with isoproterenol (5
      mg/kg) every day. The animals were sacrificed after 1 and 2 weeks, and the
      orbicularis oculi muscle and stapedius muscle were removed. Muscle fibers were
      separated into single fibers, and cytochrome oxidase enzyme staining was applied
      with 1% MnCl2, DAB + H2O2. The density of cytochrome oxidase enzyme reaction
      products and the diameter of individual muscle fibers were analyzed by computer
      assisted measurement. The administration of isoproterenol increased the activity
      of cytochrome oxidase as well as the diameter of muscle fibers in the orbicularis
      oculi muscle and stapedius muscle. It was suggested that these muscle fibers
      exhibited increases in functional activity after the administration. The results
      showed that the diameter and cytochrome oxidase enzyme activity of the
      orbicularis oculi and stapedius muscles increased. We conclude that isoproterenol
      induces hypertrophy of the orbicularis oculi and the stapedius muscle fibers, and
      promotes cytochrome oxidase enzyme activity.

PMID- 9553977
TI  - Three-dimensional imaging of laryngeal cancers using high-speed helical CT
      scanning.
AB  - To evaluate the clinical usefulness and limitations of three-dimensional (3-D)
      imaging of laryngeal cancers by high-speed helical (spiral) CT scanning, 3-D
      images were reconstructed for one dissected human larynx and 10 patients with
      laryngeal cancer. The larynges were scanned in 1- to 2-mm slices, and were
      reconstructed using a slice thickness of 0.5-1.0 mm. The macroscopic (or
      endoscopic) findings and the 3-D CT images of the larynx were compared. The
      selected threshold CT values were -600 HU (Hounsfield units) to -100 HU for the
      mucous membranes, and 250 HU for bone. Under these conditions, almost all of the
      structures remained distinct. The 3-D images of the larynx obtained by helical CT
      were very helpful in understanding laryngeal anatomy, especially in the
      subglottic area, which cannot be seen clearly by endoscopy or conventional axial
      CT. Clinically, this system would have advantages in the detection of subglottic
      cancers, or the invasion of glottic or supraglottic cancers into the subglottic
      area.

PMID- 9553978
TI  - Carotid artery reconstruction following resection during radical neck dissection.
AB  - From 1972 to 1991, 7 patients with advanced cancer of the head and neck and nodal
      metastasis with capsular rupture underwent radical neck dissection and sacrifice
      of the carotid artery. Vascular reconstruction was performed with either an
      autologous venous (8 cases) or arterial (1 case) graft. In all patients, the
      postoperative course was uneventful without neurologic complications. One patient
      is alive 4 years after the procedure. Six patients expired after a mean survival
      of 20 months. The indications for vascular reconstruction are discussed.

PMID- 9553979
TI  - Advances in the use of glass-ionomeric cement. Part 1: Experimental results and
      portrayal of a technique.
AB  - The objective of this study was to develop a method of cement microapplication
      using glass-ionomeric cement. The results of an experimental study to design a
      microapplication method of glass-ionomeric cement (Ionocem) are presented.
      Typical middle ear implant materials, as well as human temporal bones and middle
      ear ossicles, were used to test the efficiency of this application method. Two
      different versions of Ionocem, low and normal viscosity, were tested under
      different temperatures and with several application tools. Sufficient processing
      time could be achieved by cooling the cement down to 4 degrees C. A subcutaneous
      insulin syringe with a milled-off tip proved to be cost-effective, efficient and
      versatile. Using this instrument, durable and secure cementation between the
      parts tested could be achieved. This method may be of significant importance in
      otologic research and microsurgical routine. In part 2, experimental animal
      results will follow, as the method portrayed was used to secure parts of a
      totally implantable middle ear hearing device.

PMID- 9553980
TI  - Advances in the use of glass-ionomeric cement. Part 2: Functional results of fine
      application of low-viscosity glass-ionomeric cement: animal experimental results.
AB  - An experimentally developed technique for microapplication of low-viscosity glass
      ionomeric cement (see part 1) was tested in animals over a 6-month period. The
      cement was used to firmly connect gold with titanium and gold with middle ear
      ossicles in 22 adult foxhounds. After a 6-month period of acoustic stimulation
      via parts of an implantable hearing aid, the finely applied glass-ionomeric
      cement was integrated in situ, stable and caused no adverse reactions. The
      microapplication technique used proved to be easy, effective and provided long
      term stability.

PMID- 9553982
TI  - Determinants of total and specific IgE in infants with atopic dermatitis. ETAC
      Study Group. Early Treatment of the Atopic Child.
AB  - ETAC (Early Treatment of the Atopic Child), a multi-centre predominantly European
      study to investigate the potential for cetirizine to prevent the development of
      asthma in infants with atopic dermatitis has completed enrollment: 817 children
      have been randomised to 18 months' treatment with either active or placebo and a
      subsequent 18 months of post-treatment follow-up. Results of the therapeutic
      effects will not be available for some time, but the study has provided an
      opportunity to investigate influences on sensitization to allergens in a large
      cohort of 1-2 years olds with already established atopic dermatitis, resident in
      different countries and in different environments. The study shows that in
      infants with atopic dermatitis, raised serum total IgE has significantly
      different determinants from that a specific allergen sensitization. In infancy,
      increased total IgE is more affected by factors increasing risk of intercurrent
      infection and non-specific airway inflammation, such as environmental tobacco
      smoke exposure (p < 0.001) and the use of gas cookers (p = 0.02). Specific
      allergen sensitization as represented by detectable IgE antibodies is influenced
      primarily by allergen exposure. In Sweden, low level exposure to allergens is
      associated with reduced specific allergen sensitization rates even though the
      infants already have atopic dermatitis.

PMID- 9553983
TI  - Serum specific-IgE antibodies to peptides detected in a casein hydrolysate
      formula.
AB  - Up to 2.5% of infants are affected by cow milk hypersensitivity in the first two
      years of life, although most of these children will "outgrow" their reactivity
      within 2-3 years. Extensively hydrolyzed ("hypoallergenic") cow milk-based
      formulae are often recommended as a substitute formula and are generally well
      tolerated. However, a small minority of cow milk-allergic children experience
      allergic reactions to the hypoallergenic formulae as well. Utilizing inhibition
      ELISAs and sera from patients with IgE-mediated cow milk allergy, we have
      identified residual protein fractions less than 20 kD in several of the
      extensively hydrolyzed cow milk-based formulae. Although many of the cow milk
      allergic children had positive skin prick tests [SPT] to one of the hydrolysate
      formulae (Nutramigen), the positive skin test result generally did not correlate
      with clinical reactivity, although the negative predictive value of the negative
      SPT was excellent. Children with IgE-mediated cow milk allergy and a positive
      skin prick test to the hypoallergenic formula should probably receive their first
      dose of the formula in a medical setting so that appropriate therapy can be
      administered in the unlikely event of an allergic reaction.

PMID- 9553981
TI  - Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in
      children: the International Study of Asthma and Allergies in Childhood (ISAAC).
AB  - BACKGROUND: As part of the International Study of Asthma and Allergies in
      Childhood (ISAAC), prevalence surveys were conducted among representative samples
      of school children from locations in Europe, Asia, Africa, Australia, North and
      South America. SUBJECTS: 257,800 children aged 6-7 years from 91 centres in 38
      countries, and 463,801 children aged 13-14 years from 155 centres in 56
      countries. METHODS: Written symptom questionnaires were translated from English
      into the local language for self-completion by the 13-14-year-olds and completion
      by the parents of the 6-7-year-olds. Rhinitis was described as a problem with
      sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold
      or the flu. Additional questions were asked about rhinitis associated with itchy
      watery eyes, interference with activities and a history of hay fever ever.
      RESULTS: The prevalence of rhinitis with itchy-watery eyes
      ("rhinoconjunctivitis") in the past year varied across centres from 0.8% to 14.9%
      in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each
      age group, the global pattern was broadly consistent across each of the symptom
      categories. In centres of higher prevalence there was great variability in the
      proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences
      of rhinoconjunctivitis were found in parts of eastern Europe, south and central
      Asia. High prevalences were reported from centres in several regions. CONCLUSION:
      These results suggest substantial worldwide variations in the prevalence and
      labelling of symptoms of allergic rhinoconjunctivitis which require further
      study. These differences, if real, may offer important clues to environmental
      influences on allergy.

PMID- 9553984
TI  - Soy allergy is not common in atopic children: a multicenter study.
AB  - The aim of the present study was to evaluate the prevalence of soy allergy
      (positive skin test and positive challenge test) in a large cohort of atopic
      children, many of them soy fed early in life for several months. In order to
      investigate the prevalence of soy allergy, two groups of children were enrolled
      into the study. The first group comprised a cohort of 505 children with personal
      history suggestive of food allergy. The second group included 243 children born
      of atopic parents, who had been soy protein formula fed for the first six months
      of life for the prevention of cow's milk allergy and who had been prospectively
      followed up, from birth to 5 years. As regards the prevalence of soy allergy in
      the cohort of children suffering from allergic disease: 31/505 children (6%) had
      positive skin prick test to soy, however only six of the 31 children with
      positive skin prick test to soy had positive challenge test to soy. With regard
      to the prevalence of soy allergy in the children who had been soy protein formula
      fed in the first six months of life (second group): 14/243 children (6%) had
      positive skin prick test to soy, but the double blind placebo control oral food
      challenge to soy was positive in only one of these 14 children. In conclusion
      documented soy allergy is not common in atopic children.

PMID- 9553985
TI  - Lack of correlation between soluble CD14 and IL-6 in meningococcal septic shock.
AB  - Meningococcal sepsis is a good model to study the dynamic response of cytokines
      and other soluble factors in vivo in the early stages of the disease. Levels of
      soluble CD14, interleukin-6 (IL-6), IL-6 receptor (IL-6R), and C-reactive protein
      (CRP) have been measured in plasma from 26 children with septic shock (nine of
      whom had disseminated intravascular coagulation) and from ten control children.
      All samples were collected at the onset, before treatment, and, when possible, 24
      and 48 hours later. At admission, patients had significantly higher levels of IL
      6 (p < 0.001) and CRP (p < 0.001), and lower levels of IL-6R (p < 0.005) than
      normal controls. After 24 hours, there was a significant increase of sCD24 (p <
      0.05) and CRP (p < 0.001). Although IL-6 showed a progressive decline since the
      onset, its levels were always higher than controls. There was an inverse
      correlation between IL-6 and both IL-6R (p < 0.001) and CRP (p < 0.001), probably
      due to the later increase of CRP. Nevertheless, sCD14 did not correlate with IL-6
      levels. We have confirmed the finding of IL-6 as a sensitive and reliable
      inflammatory marker in septic shock. Moreover, the ratio IL-6/IL-6R may have a
      prognostic value, given a putative role of IL-6R in modulating the effects of IL
      6 in meningococcal sepsis.

PMID- 9553986
TI  - Is asthma an endocrine disease?
AB  - The prevalence of pediatric asthma has increased in many parts of the world. This
      increase started more than 30 years ago and is particularly obvious in studies
      which document the onset of asthma in native populations when they change to a
      "Western" lifestyle. Besides a genetic influence, numerous environmental factors
      have been described for the development of asthma. Genetic factors are unlikely
      to explain the sharp increase within the short time period and also allergen and
      pollution exposure or any specific infection does not actually seem to be the
      main cause for this phenomenon. Another factor, however, that fits well into the
      geographical and temporal background of the asthma epidemic is the mother's oral
      contraceptive use. We therefore review the epidemiological association with later
      asthma in the children, give a summary of estrogen effects on immune function and
      develop a preliminary theory how oral contraception could influence later
      pregnancy.

PMID- 9553987
TI  - Peroxynitrite: a putative cytotoxin.
AB  - In recent years it has become apparent that peroxynitrite, which is one of the
      toxic metabolites originating from the reaction of nitric oxide and superoxide
      presents a number of pathologic states in which free radicals are thought to be
      involved. Peroxynitrite is capable of oxidizing a wide variety of biomolecules
      including plasma, proteins, lipids, carbohydrates and nucleic acids.
      Peroxynitrite is involved in the hydroxylation of aromatic compounds and acts as
      a nitrating agent. It modifies free or protein-associated tyrosine residues to
      give nitrotyrosines, leaving a marker detectable in vivo. Peroxynitrite has been
      implicated in the pathophysiology of a variety of diseases including
      inflammation, atherosclerosis, arthritis, endotoxemia, ischaemia-reperfusion
      injury, or acute respiratory distress syndrome. Development of specific
      peroxynitrite scavengers may provide new approaches for the effective treatment
      of these disease states.

PMID- 9553988
TI  - The effect of 1,25-vitamin D3 on calbindin-D and calcium-metabolic variables in
      the rat.
AB  - Intraperitoneal injection of 1,25-(OH)2D3 4 micrograms/kg was given to 84 calcium
      and vitamin D-repleted Wistar rats and samples of plasma, duodenal mucosa and
      renal tissue were taken after 0, 3, 6, 12, 24, 48 and 96 hr (n = 12 at each time
      interval). Plasma-ionized Ca increased after 6 hr, reached a maximum after 24 hr
      and returned to the initial values after 96 hr. The concentrations of renal
      calbindin-D28k and intestinal calbindin-D9k did not increase until 48 hr after
      injection and remained elevated until 96 hr after. Therefore, significantly
      elevated concentrations of the cytosolic calbindin-D were found at a time with
      normal values of plasma Ca. The present data suggest that calbindin-D does not
      alone increase the transcellular Ca transport and, therefore, supports the view
      that calbindin-Ds may serve as Ca buffer proteins.

PMID- 9553989
TI  - Evidence for functional interactions between 5-HT1A and 5-HT2A receptors in rat
      thermoregulatory mechanisms.
AB  - The present study was designed to examine 1) functional interactions between 5
      HT1A and 5-HT2A/C receptors in thermoregulation in rats and 2) the specific
      involvement of 5-HT2A and 5-HT2C receptors in such interactions. The 5-HT2A/C
      receptor agonist DOI (0.025 1.6 mg kg-1, subcutaneously) produced a dose
      dependent hyperthermia in rats, which was enhanced by addition of either of two 5
      HT1A receptor antagonists, (-)-pindolol (0.5-1.0 mg kg-1, subcutaneously) or WAY
      100,635 (0.1-0.4 mg kg-1, subcutaneously). Furthermore, the DOI-induced
      hyperthermia was counteracted by pretreatment with the 5-HT1A receptor agonist 8
      OH-DPAT (0.05 mg kg-1, subcutaneously). The hyperthermia produced by DOI, alone
      or in combination with WAY-100,635, was fully antagonized by pretreatment with
      the 5-HT2A/C receptor antagonist ritanserin (1.0 mg kg-1, subcutaneously), as
      well as with the selective 5-HT2A receptor antagonist amperozide (2.0 mg kg-1,
      subcutaneously). The present results provide evidence for functional interactions
      between 5-HT1A and 5-HT2A receptors in temperature regulation in rats, and also
      suggest an important role for postsynaptic 5-HT2A receptors in the mediation of
      DOI-induced hyperthermia.

PMID- 9553990
TI  - Acetaminophen protection against estramustine-induced cytotoxicity on cultured
      fibroblasts.
AB  - Two commonly used analgesics, ibuprofen and acetaminophen (paracetamol) were
      investigated for possible influence on Chinese hamster fibroblast (V-79)
      cytotoxicity (measured by cells cloning ability and 86Rb accumulation) of the
      anti-neoplastic drugs estramustine and bleomycin in vitro. Fibroblast exposure to
      estramustine (80 mg/l) or bleomycin (50 mg/l), for 1 or 24 hr, reduced the number
      of surviving clones to approximately 35% and 50% respectively. Acetaminophen (10
      or 100 mg/l), but not ibuprofen, significantly increased the number of surviving
      clones with estramustine. The analgesics had no effect on bleomycin cytotoxicity.
      The uptake of 86Rb+ (K+ analogue) by V-79 cells was reduced after incubation with
      80 mg/l estramustine phosphate. Acetaminophen (30 mg/l) but not 10 mg/l
      acetaminophen or ibuprofen (30 or 100 mg/l), significantly protected against
      estramustine reduction of 86Rb accumulation. Acetaminophen inhibition of
      estramustine cytotoxicity is suggested to be due to reversal of estramustine
      induced inhibition of cellular potassium channel ion transport.

PMID- 9553991
TI  - Cross-fostering study of methyl mercury retention, demethylation and excretion in
      the neonatal hamster.
AB  - The cross-fostering technique was used in order to compare methyl mercury (MeHg)
      metabolism in hamsters following prenatal (in utero) and neonatal (lactational)
      exposure. Pregnant Syrian golden hamsters were administered radiolabeled MeHg on
      day 12 of gestation. The offspring was nursed by foster mothers unexposed to
      MeHg, while the pups from the unexposed animals were nursed by the MeHg
      administered animals. Under these conditions, each pup in the litter received a
      dose of MeHg in utero corresponding to 0.9% of the maternal dose. The average
      amount of mercury found in the pups exposed via milk corresponded to 4.5% of the
      total body burden of the foster dam at the onset of lactation. This was about
      half the amount received by the pups exposed in utero. The total body burden of
      mercury, and the amount of mercury in the liver, brain and kidney of the pups
      exposed in utero began to decrease at seven days of age. The rate of decrease
      differed among the tissues and was lowest in the kidney. The amount of mercury in
      pups exposed via milk reached a peak level when the pups were 10-15 days old. The
      total body burden of mercury showed a slow decrease while the liver, brain and
      kidney levels decreased rapidly. In both groups of animals, up to 80% of the
      total body burden of mercury was found in the pelt. These data show that milk may
      be a significant exposure route for mercury and that neonatal hamsters are unable
      to demethylate MeHg and excrete mercury in urine and faeces.

PMID- 9553992
TI  - Excitatory amino acid antagonists alleviate convulsive and toxic properties of
      lindane in mice.
AB  - Pesticides acting at GABAA receptors may induce convulsions in man and animals,
      but the mechanisms responsible for their convulsant activity are not fully
      explained. The following excitatory amino acid antagonists were studied for their
      protective action in mice intoxicated with chlorinated hydrocarbon insecticide
      lindane (gamma-hexachlorocyclohexane): the competitive NMDA antagonist: 3-(2
      carboxypiperazine-4-yl)propenyl-1- phosphonic acid (D-CPPene, 20 mg/kg), the non
      competitive NMDA antagonist: dizocilpine (MK-801, 0.4 mg/kg), the glycine site
      antagonist of NMDA receptor: 2-phenyl-1,3-propane-diol dicarbamate (felbamate,
      400 mg/kg) and the competitive AMPA antagonist: 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(F)quinoxaline (NBQX, 100 mg/kg). Systemic administration of an antagonist
      prior to lindane resulted in a strong anticonvulsant effect. D-CPPene, MK-801 and
      NBQX produced a marked increase of CD50 values of lindane for clonic convulsions.
      All the antagonists protected animals against tonic convulsions. Toxicity of
      lindane was potently reduced, as assessed 2, 24 and 120 hr after administration
      of the pesticide. Our results demonstrate that excitatory amino acid antagonists
      reduce convulsant properties and toxicity of lindane, suggesting that excitatory
      amino acid neurotransmission may be involved in its central action.

PMID- 9553993
TI  - Optimization and application of the head space liver S9 equilibration technique
      for metabolic studies of organic solvents.
AB  - A head space liver S9 vial equilibration technique for qualitative and
      quantitative metabolism of volatile organic solvents in vitro is described and
      investigated for optimal experimental conditions with toluene and n-hexane as
      model substrates. The method was also used for studying the metabolic interaction
      between acetone and styrene. NADP+ was a critical cofactor in the system as
      concentrations above 2.5 mM resulted in inhibition of metabolism. Induction of
      cytochrome P450 by phenobarbital did not alter the observed cofactor dependency,
      and addition of vehicles such as rat blood did not enhance metabolism. Acetone
      induced liver S9 increased the primary oxidation of styrene and also the
      formation of styrene oxide, but not significantly that of mandelic acid. Acetone
      as such had no effect on the metabolic elimination of styrene, indicating that
      the interaction is mainly on the level of enzyme induction occurring after long
      term exposure to acetone. As earlier reports on styrene metabolism in vivo has
      not been able to detect styrene oxide in toxicokinetic studies with a sufficient
      degree of accuracy, the head space liver S9 vial equilibration technique may
      offer a fast and sensitive tool for screening of metabolic interactions between
      organic solvents when optimized for metabolic activity.

PMID- 9553994
TI  - The effect of acute lithium and rubidium pretreatment on apomorphine-induced
      pecking in pigeons.
AB  - The effects of different doses of lithium (5-320 mg/kg intramuscularly) and
      rubidium (0.25 32 mg/kg intramuscularly) on apomorphine-induced pecking were
      investigated in pigeons. These two cations did not induce pecking by itself.
      Intramuscular administration of apomorphine (a mixed D1/D2 dopamine receptors
      agonist, 0.1-1.6 mg/kg) induced pecking in a dose-dependent manner. SCH 23390 (D1
      dopamine receptor antagonist, 0.02-0.08 mg/kg) and sulpiride (D2 dopamine
      receptor antagonist, 25-100 mg/kg) decreased apomorphine-induced pecking dose
      dependently. Combination of SCH 23390 (0.04 mg/kg) with sulpiride (50 mg/kg)
      caused a stronger inhibitory effect on apomorphine response. This indicates that
      both D1 and D2 dopamine receptors are involved in apomorphine-induced pecking.
      The response induced by apomorphine (0.2-0.8 mg/kg) was decreased in animals
      pretreated with lithium and rubidium. In these conditions, SCH 23390 and
      sulpiride produced a larger inhibitory effect on the apomorphine response,
      suggesting that acute lithium and rubidium pretreatment inhibit pecking by
      interfering with dopaminergic mechanisms.

PMID- 9553995
TI  - Prolactin response to bromperidol treatment in schizophrenic patients.
AB  - The prolactin response to an antipsychotic drug, bromperidol was studied in 24
      schizophrenic in-patients (13 males. 11 females). Eight patients were given 6
      mg/day, 8 were given 18 mg/day. Duration of treatment was 3 weeks. Plasma
      concentrations of bromperidol and reduced bromperidol were measured by high
      performance liquid chromatography, and that of prolactin was measured by
      radioimmunoassay. Bromperidol treatment significantly (P < 0.01) increased plasma
      concentration of prolactin each week. The mean +/- S.D. of the delta-prolactin
      (the mean concentration during treatment minus the pretreatment concentration)
      was 13.3 +/- 12.4 ng/ml. Multiple regression analysis showed that the delta
      prolactin concentration was significantly greater in females than in males (P <
      0.05) and correlated to plasma concentrations of bromperidol (P < 0.001) and
      reduced bromperidol (P < 0.0001). These results suggest that the prolactin
      response to bromperidol treatment depend on plasma concentrations of both
      bromperidol and reduced bromperidol and gender, and that reduced bromperidol is
      involved in the pharmacological effects during bromperidol treatment.

PMID- 9553997
TI  - Chernobyl: a survivable ecological disaster?
AB  - A study of events occurring after the Chernobyl accident until 1996 was funded by
      the European Commission (EC). The study included work by hundreds of scientists
      from the EC and the former Soviet Union. An overview of these studies is given
      that puts the science into historical context and shows the effects of the
      radioactive doses on the population and on the environment. The exposed
      populations are considered in terms of the separate exposure subgroups (emergency
      workers; inhabitants of settlements near the reactor; inhabitants of settlements
      receiving high doses of condensation radionuclides; children in the deposition
      areas; the general population). The scientific understanding of the natural and
      anthropogenic countermeasures that reduced doses is presented, and the effects on
      the human population are discussed.

PMID- 9553996
TI  - Ketobemidone plus (RS)-3-dimethylamino-1,1-diphenylbut-1-ene (A29) is more potent
      at NMDA receptors than ketobemidone alone: evidence for A29 as a non-competitive
      NMDA receptor antagonist.
AB  - The opioid, ketobemidone, has previously been shown to be a non-competitive N
      methyl-D-aspartate (NMDA) receptor antagonist. In Denmark, ketobemidone is
      available in a formulation which contains ketobemidone and a spasmolytic
      compound, (RS)-3-dimethylamino-1,1-diphenylbut-1-ene, hydrochloride (A29), in a
      one to five ratio. Using in vitro receptor binding techniques and an in vitro
      electrophysiological preparation consisting of rat cerebral cortex, we have
      characterized the interaction between A29 and the different glutamate receptor
      subtypes. A29 selectively inhibited binding of the non-competitive NMDA receptor
      antagonist 3H-MK-801 with a Ki value 16 +/- 4.5 microM, but was inactive in
      assays measuring affinities for other glutamate receptors. In agreement with the
      binding studies, A29 was found to selectively inhibit responses to NMDA in the
      rat cortical wedge preparation, whereas responses to kainate and AMPA were
      unaffected. Analysis of dose response curves showed A29 to be a NMDA receptor
      antagonist with an IC50 value of 100 microM versus responses to 10 microM NMDA.
      The inhibitory effects of ketobemidone and A29 on responses to 10 microM NMDA
      were additive. These data show that the combination of A29 and ketobemidone exert
      more potent antagonism at the NMDA receptor than does ketobemidone alone.

PMID- 9553998
TI  - The toxicologic hazard of superfund hazardous-waste sites.
AB  - Uncontrolled hazardous-waste sites are a major environmental and public health
      concern in the United States and elsewhere. The remediation of and public health
      responses to these sites is mandated by the federal Superfund statute.
      Approximately 40,000 uncontrolled waste sites have been reported to U.S. federal
      agencies. About 1,300 of these sites constitute the current National Priorities
      List (NPL) of sites for remediation. Findings from a national database on NPL
      sites show approximately 40% present completed exposure pathways, although this
      figure rose to 80% in 1996. Data from 1992 through 1996 indicate that 46% of
      sites are a hazard to public health. Thirty substances are found at 6% or more of
      sites with completed pathways. Eighteen of the substances are known human
      carcinogens or reasonably anticipated to be carcinogenic. Many of the 30
      substances also possess systemic toxicity. The high percentage of sites with
      completed exposure pathways and the toxicity potential of substances in these
      pathways show that uncontrolled hazardous-waste sites are a major environmental
      threat to human health. Findings from the United States' experience in responding
      to uncontrolled waste sites are relevant to other countries as they address
      similar environmental and public health concerns.

PMID- 9553999
TI  - Antihypertensive treatment and serum cholesterol: results of population-based
      surveys in the German Cardiovascular Prevention Study.
AB  - We analyzed the data from three cross-sectional, population-based surveys in West
      Germany to evaluate the effect of antihypertensive drug therapy on the level of
      serum cholesterol in German residents (18,344 males; 19,137 females) aged 25-69
      years, after excluding persons with missing values (N = 5529) for any study
      variable. The data were obtained from the national and regional health surveys
      that were conducted during the years 1984-1992, within the framework of the
      German Cardiovascular Prevention Study (GCP). The response rates were between
      66.0% and 71.4% for the national surveys and between 65.9% and 83.3% for the
      regional surveys. Blood-pressure and non-fasting cholesterol measurements were
      carried out under strictly standardized conditions. Multiple linear regression
      analysis was used to compare the age-adjusted mean value and prevalence for each
      of the following study variables: total serum cholesterol, HDL-cholesterol, non
      HDL cholesterol, and the ratio of HDL cholesterol/total cholesterol for users and
      non-users of antihypertensive medications. Antihypertensive medications were
      reportedly taken during the seven days preceding the survey examination by 7.8%
      of all males and 10.4% of all females. The beta-blocker type of medication was
      prescribed most frequently for lowering high blood pressure. In both genders, the
      strongest age-adjusted effect of an increase in cholesterol level was found for
      beta-blockers. The difference in the age-adjusted means for non-HDL cholesterol
      values between users and non-users of beta-blockers was 9.2 mg/dL (p < 0.001) in
      males and 9.0 mg/dL (p < 0.001) in females. Regression analysis carried out to
      control for several potential confounders confirmed the results. The findings
      suggest that mass treatment of hypertension with beta-blockers may be associated
      with reductions in benefit because of an increase in non-HDL and a decrease in
      HDL cholesterol levels.

PMID- 9554000
TI  - Molecular biomarkers of early responses to environmental stressors: implications
      for risk assessment and public health.

PMID- 9554002
TI  - Erdheim-Chester disease: radiographic findings in five patients.
AB  - We present the case histories of five patients with Erdheim-Chester disease, a
      rare lipoidosis that has several typical radiographic features. In all the
      patients, the diaphyses and metaphyses of the extremities demonstrated a
      symmetric pattern of diffuse or patchy increased density, a coarsened trabecular
      pattern, medullary sclerosis, and cortical thickening. The epiphyses were spared
      in four patients and partially involved in one. The axial skeleton was involved
      in one patient. Radiotracer 99mTc accumulated in areas of radiographic
      abnormalities in all patients. In one patient, MRI demonstrated an abnormal
      signal, corresponding to radiographic abnormalities. The signal was hypointense
      to muscle on T1-weighted sequences and heterogeneously hyperintense and
      hypointense to normal bone marrow on T2-weighted sequences. Xanthogranulomatous
      lesions infiltrated the retroperitoneum in one patient, the testes in one
      patient, the eyelids in one patient, and the orbits in two patients.

PMID- 9554001
TI  - Mastocytosis: magnetic resonance imaging patterns of marrow disease.
AB  - OBJECTIVE: To report the bone marrow MRI findings of patients with mastocytosis
      and correlate them with clinical, pathologic, and radiographic features. DESIGN
      AND PATIENTS: Eighteen patients with mastocytosis had T1-weighted spin echo and
      short tau inversion recovery MRI of the pelvis at 0.5 T. In each patient the MR
      pattern of marrow disease was classified according to intensity and uniformity
      and was correlated with the clinical category of mastocytosis, bone marrow biopsy
      results, and radiographic findings. RESULTS: Two patients had normal MRI scans
      and normal bone marrow biopsies. One patient had a normal MRI scan and a marrow
      biopsy consistent with mastocytosis. Fifteen patients had abnormal MRI scans and
      abnormal marrow biopsies. There were several different MR patterns of marrow
      involvement; none was specifically associated with any given clinical category of
      mastocytosis. Fifteen of the 18 patients had radiographs of the pelvis; of those,
      13 with abnormal MRI scans and abnormal marrow biopsies had the following
      radiographic findings: normal (nine); sclerosis (three); diffuse osteopenia
      (one). CONCLUSION: While radiographs are very insensitive for the detection of
      marrow abnormalities in mastocytosis, MRI is very sensitive and may display
      several different patterns of marrow involvement.

PMID- 9554003
TI  - MR imaging of epicondylitis.
AB  - OBJECTIVE: To systematically evaluate the MR findings in patients with
      epicondylitis compared with asymptomatic volunteers. DESIGN AND PATIENTS: We
      imaged 43 elbows: 24 with epicondylitis (22 lateral, 2 medial) diagnosed by
      clinical examination, and 19 in 16 normal volunteers. MRI was performed at 1.5 T
      using axial T1-weighted, axial fat-saturated FSE, and coronal or sagittal Fast
      STIR sequences. Two independent observers evaluated the images for intratendon
      signal, tendon thickening, periosteal reaction, fluid in the radial head bursa,
      and anconeus edema. RESULTS: All 24 patients with epicondylitis had increased
      signal on fat-saturated FSE and Fast STIR images. Twenty-two of these patients
      had increased intratendon T1 signal, and 19 had tendon thickening. No patient
      demonstrated fluid in the radial head bursa or periosteal reaction. Only two
      patients had subtle anconeus edema, while three patients unexpectedly had
      increased T2 signal within the involved epicondyle. One asymptomatic volunteer
      (high-performance athlete) had increased T1 and T2 signal with tendon thickening.
      An additional two asymptomatic volunteers had increased T1 signal only.
      CONCLUSION: MRI of epicondylitis demonstrates tendon thickening with increased T1
      and T2 signal, but these findings may be seen in a small minority of asymptomatic
      individuals. Anconeus edema, previously demonstrated on MRI in epicondylitis, was
      only rarely found, and distension of the radial head bursa, surgically described,
      was not seen. Increased marrow T2 signal within the involved epicondyle is
      occasionally seen.

PMID- 9554004
TI  - Slipped capital femoral epiphysis: a physeal lesion diagnosed by MRI, with
      radiographic and CT correlation.
AB  - OBJECTIVE: To define and compare early lesions associated with slipped capital
      femoral epiphysis (SCFE) on magnetic resonance imaging (MRI), computed tomography
      (CT) and radiography. DESIGN AND PATIENTS: Thirteen patients with 15 symptomatic
      hips due to SCFE underwent radiography and MRI; CT was performed in 12 patients.
      SCFE was graded on radiographs, head/neck angles and qualitative changes were
      evaluated on CT, and morphologic/signal abnormalities were determined on MRI.
      RESULTS: Physeal widening, apparent on T1-weighted MRI, was evident in every case
      of SCFE, including one presumed "pre-slip." T2-weighted images demonstrated
      synovitis and marrow edema but obscured physeal abnormalities. CT head/neck
      angles ranged from 4-57 degrees for symptomatic to 0-14 degrees for asymptomatic
      hips. Physeal and metaphyseal changes were variably identified on both
      radiographs and CT in all cases of SCFE, but not in the pre-slip. CONCLUSION: MRI
      clearly delineates physeal changes of both pre-slip and SCFE, and demonstrates
      very early changes at a time when radiographs and CT may appear normal.

PMID- 9554005
TI  - Chondroblastic osteosarcoma: characterisation by gadolinium-enhanced MR imaging
      correlated with histopathology.
AB  - OBJECTIVE: To identify specific features of chondroblastic osteosarcoma on
      gadopentetate dimeglumine (Gd)-enhanced magnetic resonance (MR) imaging. DESIGN
      AND PATIENTS: Nine patients with chondroblastic osteosarcoma and a control group
      of 20 patients with conventional central osteosarcoma were included in this
      study. The histopathological findings of the surgical specimens were compared
      with enhancement patterns on static Gd-enhanced MR images. RESULTS: In
      chondroblastic osteosarcoma septonodular and peripheral rim enhancement
      represented tumour with a pure chondroid matrix. Non-enhancing and heterogeneous
      enhancing areas represented tumour with both chondroid and osteoid matrix. In the
      tumours in the control group enhancement was predominantly heterogeneous but in
      one it was homogeneous. All these areas corresponded to necrotic or viable
      osteoid tumour tissue or fibrovascular tissue in areas of necrosis. CONCLUSION:
      Gd-enhanced MR imaging can assist in obtaining diagnostic biopsy material of
      chondroblastic osteosarcoma by identifying both osteoid- and chondroid-forming
      areas.

PMID- 9554006
TI  - Bizarre parosteal osteochondromatous proliferation of bone.
AB  - A 47-year-old man presented with a painless mass of 7 months' duration, on the
      plantar aspect of the great toe of the right foot. Radiographs and CT images
      initially suggested an osteochondroma arising from the proximal phalanx of the
      great toe but there was no continuity between the medullary canal of the phalanx
      and the lesion. The mass was excised and a histological diagnosis of bizarre
      parosteal osteochondromatous proliferation of bone (Nora's disease) was made. The
      aggressive growth of this lesion may clinically suggest a neoplasm. Histological
      features, however, are those of a reactive lesion.

PMID- 9554008
TI  - Parosteal osteoma of the iliac bone.
AB  - A 33-year-old patient with a 2-year history of intermittent pain in the right
      gluteal region and thigh presented with a large sclerotic lesion of the iliac
      bone. From the findings on radiography, scintigraphy, CT and MRI, a giant
      parosteal osteoma was suspected. The histological examination confirmed the
      diagnosis. Since the lesion was extensive it was observed with periodic follow-up
      examinations. At present, 5 years after the diagnosis, the patient is
      asymptomatic and imaging studies show that the lesion persists with reduction of
      sclerosis and size. The tumor was on the surface as well as intramedullary--only
      one other case with such a distribution is known to us--and it was also in the
      iliac bone.

PMID- 9554007
TI  - Recurrent parosteal osteosarcoma of the talus in a 2-year-old child.
AB  - Parosteal osteosarcoma is an uncommon, low-grade malignant bone tumor and is
      found in an older age group than conventional osteosarcoma. We present a talar
      parosteal osteosarcoma that recurred twice in a 2-year-old child. To our
      knowledge, this is the youngest patient reported with a parosteal osteosarcoma.
      The talus is an unusual site for parosteal osteosarcoma. Inadequate resection due
      to a diagnosis of juxtacortical chondroma resulted in recurrence of the tumor.
      The age of the patient, the thick cartilaginous cap, and well-differentiated
      trabecular bone all contributed to the critical erroneous diagnosis.

PMID- 9554009
TI  - Radiation-induced tibial sarcoma in a treated case of hind foot angiomatosis.
AB  - Hemangiomatosis with osteolysis, osteosclerosis and loss of bony definition is an
      uncommon disease entity. Many forms of treatment have been used, varying almost
      from case to case. The use of radiation therapy has proved successful in the
      control of the disease process in reported cases. The current case of hind foot
      hemangiomatosis went on to develop sarcoma 17 years later in the uninvolved tibia
      at the margin of the radiation field, which proved to be fatal to the patient.
      Treatment by radiotherapy had permitted normal function for 15 years. This case
      highlights the difficulties of management of skeletal angiomatosis based on
      anatomic location and emphasizes the need for judicious planning and selection of
      the mode of delivery of radiotherapy.

PMID- 9554011
TI  - Light chain deposition disease in multiple myeloma: MR imaging features
      correlated with histopathological findings.
AB  - The clinical, histopathological, and imaging findings on MRI of a 56-year-old
      woman with light chain deposition disease occurring in multiple myeloma are
      presented. Light chain deposition disease is a variant of multiple myeloma with
      distinct clinical and histological characteristics. MRI of this patient also
      revealed an infiltration pattern in the bone marrow distinct from that of typical
      multiple myeloma. Multiple small foci of low signal intensity were present on T1-
      and T2-weighted spin echo and STIR images, corresponding to conglomerates of
      light chains in bone marrow biopsy. Contrast-enhanced T1-weighted spin echo
      images show diffuse enhancement of 51% over all vertebral bodies, with a minor
      enhancement of the focal conglomerates of light chains. Light chain deposition
      disease in multiple myeloma should be added to the list of those few entities
      with normal radiographs and discrete low-signal marrow lesions on T1- and T2
      weighted spin echo pulse sequences.

PMID- 9554010
TI  - Spinal cord compression caused by thoracic vertebral hemangioma involving only
      the posterior elements of two contiguous vertebrae.
AB  - An unusual case of symptomatic thoracic vertebral hemangioma involving two
      contiguous vertebrae but confined to the posterior elements is presented. The
      lesion displaced and compressed the cord. The diagnosis was not considered prior
      to biopsy. There was uncontrolled bleeding at biopsy. Only partial surgical
      resection was performed, with incomplete relief of motor weakness after initial
      surgery. The patient refused further surgical resection. Motor power was
      gradually recovered after a course of postoperative radiotherapy.

PMID- 9554012
TI  - Sustained improvements in neurological function in spinal cord injured patients
      treated with oral 4-aminopyridine: three cases.
AB  - Preclinical trials of intravenously administered 4-Aminopyridine (4-AP) have
      demonstrated transient improvements in neurological function in patients with
      longstanding spinal cord injury (SCI). The present report describes three
      patients with SCI who responded favourably in preclinical trials and who were
      subsequently administered oral (capsule) 4-AP (10 mg b.i.d. or t.i.d.) over a 4
      month interval. The three patients (two male: 1 female) all had incomplete
      tetraplegia (ASIA levels C and D) with the neurological level of the lesion
      between C5-C7. Following the administration of 4-AP the patients demonstrated
      marked and sustained reductions in upper (n = 1) or lower extremity (n = 2)
      spasticity. Other clinical benefits of 4-AP were reduced pain (n = 1), restored
      muscle strength (n = 3), improved sensation (n = 2), voluntary control of bowel
      function (n = 1), and sustained penile tumescence (n = 2). The patients exhibited
      improved hand function (n = 1), enhanced mobility in transfers and gait (n = 2),
      with improved energy and endurance. Only trivial side effects (transient light
      headedness) were observed. In one case, the enhanced neurological function
      allowed the patient to stand with support for the first time post injury (16
      years). The time course of therapeutic response to the initial dose matched the
      pharmacokinetic elimination profile derived from serum and urine analysis. There
      was no evidence of renal or hepatic toxicity with prolonged use. These results
      indicate a therapeutic benefit of oral 4-Aminopyridine in the management of
      various neurological deficits in a select group of SCI patients.

PMID- 9554014
TI  - Medication usage in a spinal cord injured population.
AB  - The patterns of medication usage in persons with a spinal cord injury (SCI) in a
      residential facility have been studied. This population averaged over eight (8)
      medications per person, took 70% of this medication from five (5) therapeutic
      categories (MIMS) and thus took multiple medications from individual categories.
      This level of medication usage is higher than what has been published for elderly
      populations, who are considered 'at risk' of medication misadventure. The SCI
      population was predominantly young and as yet, taking few medications for
      treating age related conditions. Thus, the level of medication use might be
      expected to increase further in this population.

PMID- 9554015
TI  - Spinal hydatid disease.
AB  - Vertebral hydatid cysts are rare and found in less than 1% of all the cases of
      hydatidosis. Neural compression is common in vertebral hydatidosis. The prognosis
      is generally regarded as very poor. This paper examines the natural history and
      complications which may arise during the treatment of vertebral hydatid cyst, and
      discusses their treatment. Thirteen cases of hydatid disease affecting the
      vertebrae are presented. The patients were admitted with symptoms of spinal cord
      compression. Twelve were treated by laminectomy and one by costotransversectomy.
      Low back pain radiating to the legs and lower extremity weakness were the
      predominant symptoms. Different degrees of pareses were present in 12 patients.
      Nine patients had impaired sensation in lower extremities. In 13 patients, 27
      operations were performed. The major complication of surgery was the death of one
      patient due to the formaline irrigation. The surgical goal should be an extensive
      removal of the cysts and affected bone. The surgical area needs to be irrigated
      with hypertonic saline. Mebendazole or albendazole therapy seems to retard the
      recurrences and control the disease.

PMID- 9554013
TI  - Central cord syndrome: functional outcome after rehabilitation.
AB  - Seventy-three spinal cord injured patients with central cord syndrome who had
      undergone inpatient rehabilitation, were studied retrospectively with regard to
      their demographic, neurologic and functional characteristics. There were 67 males
      and six females with a mean age of 53.5 years. Falls was the commonest mechanism
      of injury (54.8%) followed by motor vehicle accidents. Eleven patients sustained
      cervical fractures and 41 had radiological evidence of cervical spondylosis.
      Seventeen patients had sensory impairment and significant spasticity was present
      in 14 patients. Significant improvements in the admission/discharge ASIA motor
      scores and Modified Barthel Index (MBI) scores (P < 0.001) were noted after
      rehabilitation. Ninety-two percent of patients were continent of bladder on
      discharge compared to 64.4% on admission. Multiple regression analysis revealed
      three factors associated with a better functional outcome, namely, higher
      admission MBI scores, absence of spasticity and younger age (P < 0.05).

PMID- 9554017
TI  - Iatrogenic hypospadias--a preventable injury?
AB  - Iatrogenic hypospadias is a preventable injury to the ventral male urethra
      produced by the downward pressure of an indwelling urethral catheter. In spite of
      avoiding long-term urethral catheterisation, we have acquired 16 patients with
      this injury in the last 9 years either in our unit or discovered in patients
      referred to our unit. Although not a life endangering complication, the majority
      of such patients find the penile appearance so produced unacceptable. We have
      reconstructed any penis that has more than meatal cleavage in a total of six
      patients, with good results. The majority of patients have been fully
      investigated so that an alternative therapy to catheterisation may be provided.
      Where possible a catheter free state has been achieved. If not, a suprapubic
      catheter has been inserted. Those not reconstructed were due to reasons of ill
      health, and in two instances, due to patient choice.

PMID- 9554018
TI  - Alterations in self-perceptions following childhood onset of spinal cord injury.
AB  - Most research into psychological aspects of spinal cord injury (SCI) has focused
      on adult onset. This is a retrospective study of self-perceptions following a
      childhood onset of SCI. Self-esteem, depression and self-perception were examined
      in 86 people who had a traumatic SCI before the age of 16. Depression was
      measured using the Beck Depression Inventory, and self-esteem using the Culture
      Free Self-Esteem Inventory Self-perception was measured using a scale developed
      for this study, consisting of 20 adjectives, with participants themselves on
      dimensions of 'As I am', 'As I would be without the injury', and 'as I would be
      ideally'. The participants' self perceptions of the injured self and the
      uninjured self were found to be significantly different on only nine of the 20
      adjectives. Low self-perception was found to be associated with low self-esteem
      and high depression levels, but independent of age at injury, level of injury and
      gender. The change noted by the participants between how they see themselves now
      and how they would have been without the injury is not as great as might have
      been expected.

PMID- 9554016
TI  - Long-term suprapubic catheterisation: clinical outcome and satisfaction survey.
AB  - We report on the clinical outcome and satisfaction survey of long-term suprapubic
      catheterisation in patients with neuropathic bladder dysfunction. Between early
      1988 and later 1995, 185 suprapubic catheters were inserted under direct
      cystoscopic vision. Anti-cholinergic therapy was given to all patients with
      significant detrusor hyper-reflexia; the catheters clamped daily for two hours
      and changed every six weeks. Ultrasonography and assessment of the serum
      creatinine were used to assess the upper renal tracts, and the results of the pre
      and post-catheter video-cystometrography was used to evaluate bladder
      morphology, cystometric capacity, maximum detrusor pressure and the presence of
      vesico-ureteric reflux. There were equivalent numbers of males and females. The
      follow-up ranges from 3-68 months. Following catheterisation, there was a 50%
      reduction in the average maximum detrusor pressure, bladder morphology improved
      in 85% of the cases; the bladder capacity and upper renal tracts remained
      unchanged. Vesico-ureteric reflux was abolished in 33% of the cases. Complaints
      were common consisting of recurrent catheter blockage, persistent urinary leakage
      and recurrent urinary tract infections. There was a 2.7% incidence of small bowel
      injury with one fatality. However, the general level of satisfaction was high. It
      is concluded that suprapubic catheterisation is an effective and well tolerated
      method of management in selected patients with neuropathic bladder dysfunction
      for whom only major surgery would otherwise provide a solution to incontinence.
      We are encouraged to find preservation of renal function with maintained bladder
      volumes and reduced maximum detrusor pressures thus justifying the policy of
      catheter clamping and anti-cholinergic therapy in the presence of significant
      detrusor hyper-reflexia. However, even in expert hands this procedure is not
      without hazards.

PMID- 9554019
TI  - Premature degenerative shoulder changes in spinal cord injury patients.
AB  - Shoulder pain and the resultant dysfunction is an expected problem in individuals
      with spinal cord injury. But there is a remarkable lack of information about the
      natural history, diagnosis, prevention and long term outcomes. Degenerative
      changes may develop prematurely in their shoulders, due to overuse and altered
      mechanical stresses, with or without symptoms was the hypothesis of this
      prospective study. Information from this study is expected to assist in
      identification of high risk SCI individuals, and ultimately in development of
      preventive strategies. The shoulders of 53 spinal cord injury patients from the
      onset of injury until 15 years duration were subjected to clinical and
      radiological examination at the Rehabilitation Institute of Chicago. Thirty-eight
      out of 53 (72%) patients demonstrated radiological evidence of degenerative
      changes, but only six (11%) complained of pain in the shoulders. This study
      demonstrated a correlation between individuals with higher level of wheelchair
      activity (72%), higher age (92% above and 8% less than 30 years) and female
      gender (89% females versus 65% males) more prone to develop degenerative changes
      in the shoulders. Acromioclavicular joint was predominantly affected. Detailed
      radiological findings, etiopathological factors and long term recommendations are
      discussed. The need for further studies and consistent management strategies are
      stressed.

PMID- 9554020
TI  - Epidural spinal cord stimulation for the control of spasticity in spinal cord
      injury patients lacks long-term efficacy and is not cost-effective.
AB  - Epidural spinal cord stimulation has been used to decrease spasticity and spasms
      in spinal cord injury patients. However, the long-term benefits of this procedure
      have not been determined. We therefore conducted a retrospective study of the
      possible long-term efficacy of the epidural spinal cord stimulator for the relief
      of symptoms. Seventeen patients were identified who had undergone implantation of
      an epidural spinal stimulator. The total number of implantations in these
      seventeen patients was 24, (seven patients had undergone a second implantation)
      costing a total of $566,400. In only one of the patients was the epidural
      stimulator providing symptomatic relief. The epidural spinal cord stimulator
      lacks long-term efficacy for the relief of spasticity and pain and is not cost
      effective.

PMID- 9554021
TI  - Comparison of health-related quality of life in three subgroups of spinal cord
      injury patients.
AB  - Health-related quality of life (HRQL) was evaluated in three subgroups of spinal
      cord injury (SCI) patients: (1) persons who had sustained a pediatric SCI (mean
      time from injury 20 years, age at injury 11.3 years, n = 36), (2) newly injured
      patients at the beginning of acute rehabilitation (mean age 35.3 years, n = 31),
      and (3) patients with a chronic SCI (mean time from injury 4.8 years, mean age at
      injury 35.2 years, n = 34). All the patients were clinically examined and
      structurally interviewed with a list of questions dealing with details of
      anamnestic information about injury, its treatment, possible complications and
      persons past and present psycho-social condition. HRQL was assessed by a generic
      fifteen-dimensional self-administered instrument (15D). The relative importance
      of the 15D dimensions and an overall judgement of health status were measured by
      a 0-100 visual analogue scale. Average importance weights of the dimensions of
      moving and working differed significantly in the three subgroups. Patients with
      pediatric SCI assigned the lowest importance for moving. The newly injured
      patients highly valued working capability. The HRQL scores of the patients who
      had sustained their injury in childhood were significantly higher than those of
      the newly injured patients or chronic patients. The tetraplegic patients
      estimated their HRQL significantly lower than patients with incomplete
      paraplegia. Of the three subgroups studied, those with pediatric SCI were well
      adjusted on the basis of anamnestic information and scored high on HRQL when
      compared with the other two subgroups. Patients injured in adulthood rated their
      overall HRQL lower and were often unable to return to work. Patients injured in
      childhood expressed better performance in physical functions than patients who
      had sustained their injury in adulthood. The subgroups did not differ in
      psychological functions.

PMID- 9554022
TI  - Long-term follow up in lumbar spinal stenosis.
AB  - In a retrospective study the charts of 72 patients who had decompressive surgery
      for lumbar stenosis between 1987 and 1990 were evaluated. Mean first follow up
      was 2.5 years (range 1.5 years to 3.5 years). A second follow up was done 8 years
      after surgery via mail. The mean age was 59.7 years (females 63.7, males 55
      years). The average interval between the onset of complaints to surgery was 6
      years. Claudicatio intermittens was found in 34.7% of cases. Patients were
      divided into four groups according to the classification by Arnoldi from 1976.
      Laminectomy of hemilaminectomy was performed in 73.6% of cases. In 68.1%
      nucleotomy was performed. In the first follow up outcome of patients was good in
      73.6%. Complete recovery was noted in 61.1%. 11% were not satisfied with
      operative results. Old patients especially benefitted from the operation. In the
      second follow up after 8 years only 62.1% of the patients mentioned that their
      results were unchanged, good or better than at the first evaluation. The other
      37.9% complained of a poorer result.

PMID- 9554023
TI  - Aerobic and anaerobic arm-cranking power outputs of males with lower limb
      impairments: relationship with sport participation intensity, age, impairment and
      functional classification.
AB  - Fifty individuals with lower limb impairments including spinal cord injury, polio
      and amputations underwent aerobic and anaerobic arm-cranking tests in a
      standardized laboratory setting. Based on linear regression models applied with
      age as dependent variable aerobic performance variable including HRmax (R =
      0.395, P = 0.004), and POaer (R = 0.31, P = 0.021) were subjected to ANCOVA
      adjusting for age in order to determine the significance of participation
      intensity (competitive vs leisure) and type of physical impairment. Anaerobic
      performance variables were not influenced by age and thereby subjected to 1-Way
      ANOVA with the same independent variables. Participation intensity and type of
      impairment significantly discriminated (P < 0.001) between athletes in all power
      variables. Linear regression models have shown moderate but significant (P <
      0.001) relationship with functional ability (bases on International Wheelchair
      Basketball Federation classification system). In anaerobic mean power (MP)
      classification accounted for 42% of the variance, while in anaerobic peak power
      (PP) and aerobic Power (POaer) for 38% and 30% respectively. By means of a post
      hoc Tukey analysis significant differences were observed between athletes with a
      high level paraplegia (class 1) and those with one leg affected by polio or
      amputations (classes 4, 4.5). Athletes with low level paraplegia and two legs
      affected by polio (classes 2-3.5) had values in-between. Based on the descriptive
      evaluation, a three group scheme was conceptualized and resubjected to ANOVA.
      Significant intergroup differences were thus obtained only for PP. Descriptive PP
      data for each group were transformed into a five category table in order to
      provide reference values for fitness-estimation in males with lower limb
      impairments of various etiologies.

PMID- 9554024
TI  - Problems, struggles and some success with spinal cord injury in Zimbabwe.
AB  - Spinal cord injury is a common occurrence in Zimbabwe and carries with it a high
      morbidity and mortality. In the past almost all patients discharged from hospital
      were dead within a year. Reasons for this high mortality are presented. The
      establishment of the National Rehabilitation Centre has had a profound impact on
      the survival of these individuals as well as on improving their quality of life.
      The results of a retrospective survey on the mortality and life situation of
      individuals with spinal cord injuries sustained through trauma are presented.
      However major unresolved problems are inadequate housing, lack of financial
      support, practically no prospect of employment and depression compounded by
      boredom.

PMID- 9554025
TI  - Electrocardiographic alterations associated with the hearts of athletes.
AB  - Physical conditioning induces numerous cardiovascular adaptations, including
      vagotonia and increased cardiac volume and mass. These adaptations characterise
      the 'athletic heart' and account for most of the normal variants in the athlete's
      electrocardiogram. Common alterations associated with vagotonia include sinus
      bradycardia, sinus arrhythmia, junctional escape beats, first degree
      atrioventricular block and second degree (Mobitz type I) atrioventricular block.
      Common electrocardiographic variants associated with increased cardiac mass and
      volume include increased voltage, prominent U waves, intraventricular conduction
      delays, early repolarisation and increased QT intervals. It is sometimes
      difficult to differentiate the healthy athlete with an athletic heart from the
      athletic patient with a diseased heart. Thus, further evaluation may be
      warranted, especially when the athlete also presents with hypertension and/or
      abnormalities of the cardiovascular physical examination.

PMID- 9554026
TI  - Proprioception of the ankle and knee.
AB  - Proprioception and accompanying neuromuscular feedback mechanisms provide an
      important component for the establishment and maintenance of functional joint
      stability. Neuromuscular control and joint stabilisation is mediated primarily by
      the central nervous system. Multisite sensory input, originating from the
      somatosensory, visual and vestibular systems, is received and processed by the
      brain and spinal cord. The culmination of gathered and processed information
      results in conscious awareness of joint position and motion, unconscious joint
      stabilisation through protective spinal-mediated reflexes and the maintenance of
      posture and balance. Clinical research aimed at determining the effects of
      articular musculoskeletal injury, surgery and rehabilitation, on joint
      proprioception, neuromuscular control and balance has focused on the knee and
      ankle joints. Such studies have demonstrated alterations in proprioception
      subsequent to capsulo-ligamentous injury, partial restoration of proprioceptive
      acuity following ligamentous reconstruction, and have suggested beneficial
      proprioceptive changes resulting from comprehensive rehabilitation programmes.

PMID- 9554027
TI  - Fluid and carbohydrate replacement during intermittent exercise.
AB  - Most studies relating to fluid replacement have addressed the problem of drinking
      during prolonged exercise. Fluid replacement is also very important for
      intermittent exercise, although it has not been extensively studied. More studies
      in this area would help coaches and athletes understand the importance of fluid
      balance and carbohydrate supplementation during intermittent exercise. Based on
      available data, it can be concluded that: (i) because of high exercise intensity,
      sweat loss and glycogen depletion during intermittent exercise are at least
      comparable with those during continuous exercise for a similar period of time.
      Therefore, the need to ingest a sport drink or replacement beverage during
      intermittent exercise may be greater than that during continuous exercise in
      order to maintain a high level of performance and to help prevent the possibility
      of thermal injury when such activity occurs in a warm environment; (ii) the
      volume of ingested fluid is critical for both rapid gastric emptying and complete
      rehydration; and (iii) osmolality (250 to 370 mOsm/kg), carbohydrate
      concentration (5 to 7%), and carbohydrate type (multiple transportable
      carbohydrates) should be considered when choosing an effective beverage for
      rehydration and carbohydrate supplementation during intermittent exercise.

PMID- 9554032
TI  - Use of the zebrafish (Danio rerio) to define hematopoiesis.
AB  - Hematopoiesis in the vertebrate is characterized by the induction of ventral
      mesoderm to form hematopoietic stem cells and the eventual differentiation of
      these progenitors to form the peripheral blood lineages. Several genes have been
      implicated in the differentiation and development of hematopoietic and vascular
      progenitor cells, yet our understanding of the discrete steps involved in the
      induction of these cells from the ventral mesoderm is still incomplete. One
      method of delineating these processes is based on the use of lower vertebrates.
      The zebrafish (Danio rerio) is an especially robust vertebrate system for both
      isolating and characterizing genes involved in these processes. Hematopoietic
      mutants have been generated with defects in many of the steps of both the
      primitive and definitive hematopoietic programs. Cloning of the genes that
      underlie these mutations should yield valuable details of hematopoiesis and may
      have therapeutic implications for bone marrow transplantation and stem cell gene
      therapy.

PMID- 9554030
TI  - Shoulder injuries from alpine skiing and snowboarding. Aetiology, treatment and
      prevention.
AB  - There has been a decrease in the overall injury rate and the rate of lower
      extremity injuries for alpine skiing, with a resultant increase in the ratio of
      upper extremity to lower extremity injuries. Upper extremity injuries account for
      20 to 35% of all injuries during alpine skiing and nearly 50% of all injuries
      during snowboarding. The most common upper extremity injuries during skiing are
      sprain of the thumb metacarpal-phalangeal joint ulnar collateral ligament, and
      the most common in snowboarding is wrist fracture. Shoulder injuries from skiing
      and snowboarding have been less well characterised. With the increased ratio of
      upper to lower extremity injuries during alpine skiing and the boom in popularity
      of snowboarding, shoulder injuries will be seen with increasing frequency by
      those who care for alpine sport injuries. Shoulder injuries account for 4 to 11%
      of all alpine skiing injuries and 22 to 41% of upper extremity injuries. The rate
      of shoulder injuries during alpine skiing is 0.2 to 0.5 injuries per thousand
      skier-days. During snowboarding, shoulder injuries account for 8 to 16% of all
      injuries and 20 to 34% of upper extremity injuries. Falls are the most common
      mechanism of shoulder injury, in addition to pole planting during skiing and
      aerial manoeuvres during snowboarding. Common shoulder injuries during skiing and
      snowboarding are glenohumeral instability, rotator cuff strains,
      acromioclavicular separations and clavicle fractures. Less common shoulder
      injuries include greater tuberosity fractures, trapezius strains, proximal
      humerus fractures, biceps strains, glenoid fractures, scapula fractures, humeral
      head fractures, sterno-clavicular separations, acromion fractures and biceps
      tendon dislocation. Prevention of shoulder injuries during skiing and
      snowboarding may be possible through interventions in education and technique,
      conditioning and equipment and environment.

PMID- 9554031
TI  - An intricate Web: chemokine receptors, HIV-1 and hematopoiesis.
AB  - Cellular infection by the human immunodeficiency virus type 1 (HIV-1) requires
      interaction of the viral envelope protein with CD4 and at least one additional
      cell surface molecule, termed a "cofactor" or "coreceptor." Recent discoveries
      have determined that macrophage-tropic strains of HIV-1 which are largely
      responsible for sexual transmission require the beta-chemokine receptor CCR5 in
      addition to CD4, while the T cell tropic viruses that emerge later after
      infection use the alpha-chemokine receptor CXCR4. Thus, both CD4 and the
      appropriate chemokine receptor must be expressed on the cell surface in order for
      HIV-1 to enter the cell and establish an infection. The in vivo importance of
      CCR5 for HIV-1 is demonstrated by the finding that individuals homozygous for a
      32 bp deletion (delta 32) in the CCR5 gene that renders them effectively CCR5
      negative are highly resistant to virus infection. In this review, the structure
      function correlates of the chemokine receptors that serve as major coreceptors
      for HIV-1 and simian immunodeficiency virus entry will be reviewed. Since certain
      chemokines have been implicated as stem cell inhibitory factors, the biological
      consequences of chemokine receptor expression as it relates to HIV-1-associated
      hematodyspoiesis will also be discussed.

PMID- 9554029
TI  - Impact of resistance training on endurance performance. A new form of cross
      training?
AB  - In accordance with the principles of training specificity, resistance and
      endurance training induce distinct muscular adaptations. Endurance training, for
      example, decreases the activity of the glycolytic enzymes, but increases
      intramuscular substrate stores, oxidative enzyme activities, and capillary, as
      well as mitochondrial, density. In contrast, resistance or strength training
      reduces mitochondrial density, while marginally impacting capillary density,
      metabolic enzyme activities and intramuscular substrate stores (except muscle
      glycogen). The training modalities do induce one common muscular adaptation: they
      transform type IIb myofibres into IIa myofibres. This transformation is coupled
      with opposite changes in fibre size (resistance training increases, and endurance
      training decreases, fibre size), and, in general, myofibre contractile
      properties. As a result of these distinct muscular adaptations, endurance
      training facilitates aerobic processes, whereas resistance training increases
      muscular strength and anaerobic power. Exercise performance data do not fit this
      paradigm, however, as they indicate that resistance training or the addition of
      resistance training to an ongoing endurance exercise regimen, including running
      or cycling, increases both short and long term endurance capacity in sedentary
      and trained individuals. Resistance training also appears to improve lactate
      threshold in untrained individuals during cycling. These improvements may be
      linked to the capacity of resistance training to alter myofibre size and
      contractile properties, adaptations that may increase muscular force production.
      In contrast to running and cycling, traditional dry land resistance training or
      combined swim and resistance training does not appear to enhance swimming
      performance in untrained individuals or competitive swimmers, despite
      substantially increasing upper body strength. Combined swim and swim-specific 'in
      water' resistance training programmes, however, increase a competitive swimmer's
      velocity over distances up to 200 m. Traditional resistance training may be a
      valuable adjunct to the exercise programmes followed by endurance runners or
      cyclists, but not swimmers; these latter athletes need more specific forms of
      resistance training to realise performance improvement.

PMID- 9554033
TI  - Characterization of natural suppressor cells in human bone marrow.
AB  - Natural suppressor (NS) cells, which exert nonspecific suppressive activity in an
      unprimed manner, have been found in mouse, rabbit and monkey bone marrow (BM). In
      the present study, we characterize NS cells in human BM. NS activity was found in
      a fraction of low density (1.055-1.065 g/ml) BM cells that had been depleted of T
      cells, B cells, and monocytes. The NS activity was significantly decreased by the
      depletion of CD34+ or CD33+ cells but not CD56+ cells. The NS activity was indeed
      detected in isolated CD34+ cells and further enriched in CD34+CD33+ cells.
      Hematopoietic progenitor cells committed to the myeloid lineage were also
      enriched in the CD34+CD33+ cells, which significantly correlated to the NS
      activity. From these findings, it is strongly suggested that NS activity in human
      BM is exerted by the myeloid hematopoietic progenitors. Since cell-to-cell
      contact was not necessary for the action, NS cells seemed to secrete soluble
      mediator(s). Transforming growth factor-beta 1 and leukemia inhibitory factor
      were, however, not the candidates, based on experiments using neutralizing
      antibodies.

PMID- 9554028
TI  - The effects of strength training and disuse on the mechanisms of fatigue.
AB  - Increases in force, electromyography, reflex potentiation, muscle action
      potential amplitude and protein synthesis occur with strength training. Training
      induced increases in the efficiency of the neuromuscular system and capacity of
      the muscle to generate force result in an improved ability to cope with a
      submaximal load. There is also some evidence of improved fatigue resistance with
      maximal contractions which could be attributed to a prolongation of membrane
      excitation or decreased antagonist activity with training. On the other hand,
      although a variety of factors including strength are diminished with disuse, a
      number of studies have demonstrated no significant difference in the rate of
      fatigue with maximal contractions (fatigue index) between trained, untrained and
      disused muscle. Equivalent control and disuse fatigue indexes in some studies
      might be attributed to decreased muscle activation resulting in a comparison of
      maximal (control) and submaximal (disuse) efforts. Furthermore, increases in the
      duration of muscle membrane electrical propagation with disuse may increase the
      quantity of Ca++ released, augmenting force production. In addition, the smaller
      volume of disused muscle may allow a more efficient diffusion of oxygen and
      energy substrates in comparison with a hypertrophied muscle.

PMID- 9554034
TI  - Estimation of extent of cell death in different stages of normal murine
      hematopoiesis.
AB  - Murine hematopoiesis has been analyzed by many authors, and available data allow
      for quantitative evaluation of this dynamic process. In this study, the capacity
      of several populations of the bone marrow clonogenic cells (progenitors) to
      produce blood cells was compared with their actual production. The cell cycle
      progression rate was directly measured in the following types of hematopoietic
      progenitors: day 8 colony-forming units-spleen, GM-colony-forming cells, BFU-E,
      and CFU-E in normal mice. The cell cycle progression rates of the individual
      progenitors, together with their numbers in the whole hematopoietic tissue, were
      used to calculate the absolute numbers produced daily in each population. The
      data reviewed from literature were analyzed in parallel. The capacity of the
      progenitors to produce mature blood cells were derived from the daily production
      of progenitors multiplied by their clonogenic potential. This theoretical
      capacity to produce blood cells was compared to the actual blood cell production
      determined from the turnover of circulating blood elements. The comparison
      strongly suggested an intensive cell death rate occurring at the early stages of
      differentiation and its decline as the hematopoietic cells become more
      differentiated and mature.

PMID- 9554035
TI  - Stem cell factor improves the repopulating ability of primitive hematopoietic
      stem cells after sublethal irradiation (and, to a lesser extent) after bone
      marrow transplantation in mice.
AB  - Bone marrow transplantation (BMT) and sublethal irradiation (XRT) cause profound
      long-term damage to hematopoietic stem cells. We used the competitive
      repopulation assay in mice to test the ability of granulocyte-macrophage colony
      stimulating factor (GM-CSF) and stem cell factor (SCF), cytokines given in
      clinical settings to enhance marrow recovery after XRT or BMT and to protect the
      marrow repopulating ability of primitive hematopoietic stem cells (PHSC) after
      these modalities. The repopulating ability of exhaustible multilineage
      progenitors (EMP) was also tested after these modalities, with or without
      cytokines. Repopulating abilities of EMP and PHSC were significantly reduced
      after XRT or BMT; PHSC were preferentially affected. Administration of SCF to
      C57B6/J mice after XRT resulted in improved EMP and PHSC repopulating ability,
      although progenitor numbers--repopulating units--were not completely returned to
      control levels. Whether given as a single dose or multiple doses, GM after XRT
      did protect PHSC function from the deleterious effects of XRT, but this was not a
      significant effect. SCF caused an increase in PHSC repopulating ability after
      BMT, but this too was not a significant difference. GM after BMT had little
      effect. SCF administration before XRT led to severe impairment of PHSC function
      with very little or no stem cell activity observed. Therefore, timing of its
      administration is an important consideration since preadministration of the
      cytokine before XRT can be extremely harmful to PHSC function.

PMID- 9554036
TI  - Cell adhesion molecule expression in cord blood CD34+ cells.
AB  - Self-renewal, proliferation, differentiation, homing, and mobilization of
      hematopoietic progenitor cells (HPCs) are regulated by a complex mechanism that
      involves the bone marrow (BM) microenvironment. Cell adhesion molecules (CAMs)
      expressed on HPCs and on endothelial and stromal cells play a pivotal role in
      this process. In this study, we have used three-color cytofluorometric analysis
      to compare CAM expression in the subsets of cord blood (CB) and BM HPCs and
      examined the effect of a short exposure to various cytokines on L-selectin
      expression. The study was carried out on unseparated samples to avoid any
      possible bias from positive CD34 selection. CAMs were highly expressed in both CB
      and BM CD34+CD38+ cells. In this population, L-selectin, H-CAM, and LFA-1 were
      significantly more expressed in BM than in CB. With regard to the more immature
      progenitors, the subsets of CD34+/CD38-/L-selectin+ and CD34+/CD38-/LFA1+ cells
      were significantly larger in CB than in BM. Since the expression of such CAMs has
      been related to the repopulating capacity of HPCs, our results suggest a possible
      advantage in homing and engraftment of more undifferentiated CB as opposed to BM
      HPCs. A 4/24-h exposure to various cytokines significantly increased the
      percentage of CB CD34+/CD38+/L-selectin+ cells, while HPCs were differentiated
      since the percentage of CD34+/CD38-/L-selectin+ cells was reduced. These data
      show that a short exposure to cytokines increases L-selectin expression in the
      more differentiated CB HPCs. This could improve their homing in a transplant
      setting.

PMID- 9554037
TI  - Kinetics of hematopoiesis in Dexter-type long-term cultures established from
      human umbilical cord blood cells.
AB  - In the present study, we have established Dexter-type long-term cultures (D-LTC)
      from human umbilical cord blood (UCB) and followed the kinetics of different
      hematopoietic progenitor cells (HPCs)--including multipotent (colony forming unit
      [CFU]-Mixture), erythroid (CFU-erythroid, BFU-E), and myeloid (CFU-granulocyte,
      CFU-macrophage, CFU-granulocyte/marcophage) progenitors as well as of
      morphologically recognizable erythroid, myeloid and lymphoid cells--during a nine
      week culture period. D-LTC were also established from adult bone marrow (BM) as
      controls. On day 0, both UCB and BM showed similar total numbers of HPCs (about
      310/10(5) cells), however, UCB showed a higher proportion of primitive HPCs
      (i.e., CFU-Mixture, CFU-granulocyte/macrophage and BFU-E). A poor adherent cell
      layer, consisting almost exclusively of macrophages, was developed in UCB D-LTC
      and this correlated with a continuous decline in HPC numbers throughout the
      culture period. In contrast, adherent cell numbers in BM D-LTC, including
      fibroblasts and macrophages, were two- to fourfold higher than in UCB cultures,
      and the numbers of HPCs were also significantly higher, reaching plateau levels
      between weeks 6 and 9. In both types of cultures, erythroid and multipotent
      progenitors declined relatively fast, reaching undetectable levels after five
      weeks of culture. Myeloid progenitors, on the other hand, were sustained longer
      (always at higher levels in BM cultures) and were still detected by week 9. Among
      myeloid progenitors, a shift towards the predominance of macrophage HPCs was
      observed, both in UCB and BM D-LTC, and this correlated with an increase in the
      proportion of mature monocytes and macrophages. Taken together, our results
      indicate that myeloid progenitor cell growth is deficient in UCB D-LTC and
      suggest that this is due to the impaired development of an adherent cell layer,
      unable to provide the factors and conditions required for their growth.
      Interestingly, throughout the culture period the total numbers of multipotent and
      erythroid progenitors were similar both in UCB and BM cultures regardless of the
      number and types of adherent cells present; this suggests that the stroma
      developed in D-LTC is not sufficient for the proliferation of these progenitor
      cells.

PMID- 9554040
TI  - Simplified retroperfusion system preserves the myocardial function during acute
      coronary artery occlusion.
AB  - It is known that coronary venous retroperfusion restores the blood flow to the
      ischemic myocardium, resulting in reduction of infarct size and improvement in
      left-ventricular pump function. In this study, we used an animal model to
      investigate the effects of a simplified coronary venous retroperfusion system on
      myocardial hemodynamics. Twenty dogs were entered in this study. All dogs
      underwent fifteen minutes occlusion of the left anterior descending artery. For
      the rest of the experiment the dogs were randomized into two groups: the control
      group (n = 10) underwent a further 2 hours left anterior descending artery
      occlusion, then clamps were released and the animals were observed for 6 hours.
      In the retroperfusion group (n = 10) a simple aortocoronary sinus connection was
      made and retrograde perfusion achieved with an outflow of 43 +/- 6 ml/min.
      Retrograde coronary sinus perfusion was maintained for three hours and then the
      dogs were observed for six hours. Tissue adenosine triphosphate levels were 6 +/-
      3 mumol/g in the control group and 12 +/- 2 mumol/g in the retroperfusion group
      (p < 0.05) 6 hours after reperfusion. Creatine phosphokinase levels were 99 +/-
      11 IU/L in the control group and 42 +/- 8 IU/L in the retroperfusion group 6
      hours after reperfusion (p < 0.05). Cardiac index was 63 +/- 4 ml/kg/min in the
      control group and 79 +/- 2 ml/kg/min in the retroperfusion group 6 hours after
      retroperfusion (p < 0.05). Left-ventricular stroke-work index at a pulmonary
      capillary artery wedge pressure of 20 mmHg was 0.54 +/- 0.06 g.m/kg in the
      retroperfusion group and 0.29 +/- 0.03 g.m/kg in the control group 6 hours after
      reperfusion (p < 0.05). It is concluded that myocardial hemodynamic and
      biochemical function can be preserved by simplified coronary sinus
      retroperfusion.

PMID- 9554038
TI  - Identification by differential display of transcripts regulated during
      hematopoietic differentiation.
AB  - The polymerase chain reaction-based differential display method (DDRT-PCR) was
      used to identify mRNAs differentially expressed during the maturation of human
      CD34+ progenitor cells stimulated to differentiate in vitro towards
      granulomonocytic or erythroid lineages with a mixture of hemopoietins (kit ligand
      + interleukin 3 + GM-CSF in the absence or presence of erythropoietin,
      respectively). Three cDNA transcripts (B32, B41, and B56) display differential
      expression during cytokine-induced maturation of CD34+ cells. These clones have
      no homology with already-described sequences. Primer extension cofirmed the
      presence of the corresponding mRNA. The levels of mRNA corresponding to B32 are
      enhanced in the later phases of the granulomonocytic as well as in the erythroid
      differentiation of CD34+ cells. The mRNA identified by B41 was induced by a late
      stage in only granulomonocytic differentiation of CD34+ cells. The mRNA
      corresponding to B56 was instead present in nonstimulated CD34+ cells, declined
      in the early stages of differentiation, and reappeared at later stages in cells
      treated with both combinations of cytokines. Expression of these genes was
      detected in a number of acute myelogenous leukemias, as well as in some leukemic
      cell lines. B32 and B41 were downregulated in KG-1 cells induced to differentiate
      towards the monocytic lineage, whereas the levels of B56 were unchanged. In K562
      cells, clones B41 and B56 were downregulated only in the late phases of PMA
      induced megakaryocytic differentiation and during erythroid differentiation. B32
      was rapidly downregulated when K562 cells were induced to differentiate towards
      either megakaryocytic or erythroid phenotypes. These transcripts represent novel
      hematopoietic cDNAs that should prove of value for the study of human blood cells
      and their disorders.

PMID- 9554039
TI  - Influence of rhG-CSF scheduling on megakaryocytopoietic recovery following 5
      fluorouracil-induced hematotoxicity in splenectomized B6D2F1 mice.
AB  - Recombinant human granulocyte colony-stimulating factor, rhG-CSF, is widely
      applied to ameliorate neutropenia following chemotherapy. However, rhG-CSF can
      exert negative effects on megakaryocytopoiesis that might cause a delay of
      megakaryocyte recovery. Therefore, the present study was designed to test
      different rhG-CSF administration protocols with regard to their megakaryocytic
      inhibitory potential in a 5-fluorouracil (5-FU)-induced experimental model
      system. Splenectomized B6D2F1 mice received a single injection of 5-FU (150
      mg/kg) on day 0 followed by 50 micrograms/kg/day rhG-CSF given daily for either
      zero, four, or eight days. Five days after 5-FU, bone marrow and blood
      hematopoiesis were reduced significantly when compared with controls, independent
      of whether or not animals received rhG-CSF. However, nine days after 5-FU,
      granulopoietic recovery from 5-FU-induced toxicity was faster for rhG-CSF-treated
      versus untreated mice as demonstrated by higher values for colony forming unit
      granulocyte macrophage (CFU-GM) and granulocytes (CFU-GM: 7.2 +/- 0.4 versus 5 +/
      0.6 x 10(4)/femur, granulocytes: 4.3 +/- 2 versus 1.4 +/- 0.4 x 10(5)/ml,
      respectively). Furthermore, significant mobilization of CFU-megakaryocyte (CFU
      Meg) and CFU-GM into the peripheral blood was induced by the eight-day
      administration of rhG-CSF following 5-FU (day 9: 911 +/- 102 CFU-Meg/ml, 2330 +/-
      152 CFU-GM/ml). However, megakaryocytic cells in these same mice were
      considerably lower when compared with those of animals receiving no rhG-CSF (CFU
      Meg: 2.7 +/- 0.2 x 10(3) versus 4.2 +/- 0.2 x 10(3)/femur; small
      acetylcholinesterase positive (SAChE+) cells: 4.9 +/- 0.3 x 10(3) versus 7.3 +/-
      0.9 x 10(3)/femur; megakaryocytes: 2.5 +/- 0.2 x 10(3) versus 4.1 +/- 0.7 x
      10(3)/femur; platelets: 2.67 +/- 0.5 x 10(9) versus 3.1 +/- 0.5 x 10(9)/ml,
      respectively). On the other hand, the shortening of the rhG-CSF treatment from
      eight to four days caused a rapid granulopoietic recovery comparable to animals
      receiving eight days of G-CSF with no significant delay in megakaryocytic
      recovery when compared with mice treated with 5-FU alone; however, with four days
      of rhG-CSF, the mobilization of CFU into the peripheral blood was significantly
      less effective. Taken together, the results showed that a shortening of rhG-CSF
      treatment after chemotherapy is capable of ameliorating neutropenia without
      negatively affecting megakaryocytopoietic recovery. If, however, maximum
      recruitment of CFU into the peripheral blood circulation by rhG-CSF for
      subsequent harvest and transplantation is needed, any shortening of rhG-CSF
      administration is not advisable.

PMID- 9554041
TI  - An assessment of selective cerebral perfusion via the innominate artery in aortic
      arch replacement.
AB  - Maintaining an adequate cerebral oxygen supply is a serious problem in aortic
      arch surgery. Deep hypothermic circulatory arrest is the most common method used
      for cerebral protection, but guarantees only a time-limited safety period. Based
      on experimental investigations, we applied selective cerebral perfusion via the
      innominate artery alone with only moderate hypothermia (28 degrees C) and without
      circulatory arrest in 25 consecutive patients undergoing surgical treatment of an
      aneurysm (n = 10) or acute type-A dissection (n = 15) involving the aortic valve
      and arch. In every case a test perfusion was carried out to assess whether the
      cerebral perfusion achieved would be adequate for the whole operation. In no case
      was the perfusion inadequate. As a new perioperative monitoring system, we used
      computer-aided topographical electroencephalometry (CATEEM). There were 18 male
      and 7 female patients, their age was 47.0 +/- 15.1 years (mean +/- SD). Mean time
      periods were 155.1 +/- 37.3 min for aortic cross-clamping, and 69.3 +/- 35 min
      for selective cerebral perfusion. Postoperatively, two patients (8%) revealed a
      temporary left-sided hemiparesis, and 4 patients (16%) died within 30 days. The
      overall mortality rate was 16% in a follow-up period of 24.2 +/- 9.5 months. In
      this small group the CATEEM monitoring enabled an intraoperative selection of
      patients with sufficient bihemispheric collateral circulation and therefore
      suitable for simple innominate artery perfusion.

PMID- 9554042
TI  - Composite graft replacement of the aortic root in 335 patients with aneurysm or
      dissection.
AB  - The hypothesis that replacement of the aortic root with a valved composite graft
      is a safe and effective therapy for aneurysms involving the sino-tubular segment
      of the aorta was tested by a retrospective review. From September 1978 to January
      1995, 335 consecutive patients underwent prosthetic aortic root replacement as
      the primary operation for aneurysm (222) or dissection (acute 59, chronic 54).
      There were 248 men (74%) and 87 women (26%) with a mean age of 50 +/- 14 years.
      22 patients (6.6%) experienced hospital death primarily due to cardiac causes.
      Mortality was significantly higher in patients with acute dissection versus those
      with non-dissecting aneurysms and chronic dissection. Sex, Marfan syndrome (20.3%
      of patients), mitral regurgitation, coronary artery disease, and era of operation
      had no effect on early outcome. Mortality was significantly increased in patients
      aged over 50 years, in those with circulatory compromise, and in patients
      requiring emergency operation. Follow-up was complete in 313 survivors (97%) at a
      mean of 61.3 +/- 44 months. Actuarial survival was 80% at 5 and 67% at 10 years.
      There were no complications involving the coronary anastomoses, other than
      infection-related, regardless of the mode of ostial reattachment.

PMID- 9554043
TI  - Risk indicators for cerebrovascular complications after coronary artery bypass
      grafting.
AB  - All patients from western Sweden were retrospectively studied in whom CABG was
      performed between June 1, 1988 and June 1, 1991 without simultaneous valve
      surgery. The aim was to detect clinical factors prior to and at the time of
      coronary artery bypass grafting (CABG) which were associated with the risk of
      neurological complications during the postoperative hospital stay. A neurological
      complication during the hospital stay was registered if a neurological
      consultation was made and if this consultation diagnosed a neurological deficit.
      In all, there were 2121 patients in the study, of whom 81 (3.8%) had a
      neurological complication. 23 of the latter (28%) died before discharge. Among
      preoperative factors the following appeared as significant independent predictors
      of a neurological complication: a history of cerebrovascular disease (p < 0.001),
      diabetes mellitus (p < 0.01), hypertension (p < 0.05), degree of urgency of the
      operation (p < 0.01), and age (p < 0.01). Among pre- and post-operative events
      the following predicted a neurological complication: intensive care unit
      treatment for more than two days (p < 0.001) and respirator required for more
      than 24 hours (p < 0.001).

PMID- 9554044
TI  - An experimental approach to quantitative thermal coronary angiography.
AB  - Thermal coronary angiography is a noninvasive but not yet quantitative method to
      intraoperatively assess graft patency in CABG surgery. Aim of this study was to
      quantify graft flow by measuring perfusion-induced myocardial temperature changes
      over time. Saphenous vein grafts to the left anterior descending artery were
      perfused at flow rates of 16-105 ml/min with warm saline. A thermal scanner with
      a 256 x 256 focal-plane array detector providing a spatial resolution of 1.2 mrad
      was used. The resulting temperature curves were averaged and a non-linear fit
      procedure was performed to calculate the time constant (tau) at each flow rate.
      An increase of myocardial temperature along the LAD with different flow rates
      could be demonstrated. There was an excellent correlation between the calculated
      time constant and actual flow (r = 0.96, p < 0.0002). By determining the time
      constant for different flow rates an estimate of actual graft flow is possible
      using thermal coronary angiography. Clinical studies have to show if the time
      constant can be used as a predictor of graft flow in patients.

PMID- 9554045
TI  - Preconditioning enhances myocardial protection in patients undergoing open heart
      surgery.
AB  - To date, ischemic preconditioning is regarded as the most powerful form of
      endogenous myocardial protection. For the purpose of surgical myocardial
      protection, a few clinical studies have investigated the effects of ischemic
      preconditioning in conjunction with hypothermia or blood cardioplegia during open
      heart surgery, but the results were controversial. We now tested the hypothesis
      that preconditioning improves myocardial protection in patients undergoing cold
      crystalloid cardioplegic arrest. 36 patients needing mitral prosthetic valve
      replacement for rheumatic heart disease were studied. Patients were evenly
      divided into two groups at random. Preconditioning was elicited by two cycles of
      3 minutes ischemia by occlusion of vena cava and aortic cross-clamping followed
      by 2 minutes reperfusion under cardiopulmonary bypass. All hearts were arrested
      using 4 degrees C St. Thomas' Hospital solution before the intracardiac operative
      program. Myocardial protective effects were mainly assessed by electrocardiac
      activities, leakage of myocardial enzymes, myocardial contractility, and early
      postoperative recovery. The results indicated that there was a significant
      reduction of ST-segment shifting (ST-segment elevation, 0.07 +/- 0.02 vs 0.22 +/-
      0.07 mV, p < 0.05, at 4 hours post reperfusion) and smaller release of creatine
      kinase-MB (87 +/- 11.5 vs 143 +/- 17.2 IU/L, p < 0.05, at 12 hours post
      reperfusion) in the preconditioning group. Preconditioning also enhanced
      myocardial contractility (dp/dtmax = 1490 +/- 75 vs 1280 +/- 88 mmHg/sec, at 30
      minutes post reperfusion, p < 0.05) and promoted early postoperative recovery.
      The present study suggests that ischemic preconditioning reduces ischemia
      reperfusion injury in human hearts even when combined with cold crystalloid
      cardioplegia.

PMID- 9554046
TI  - Everting closure for interrupted aortic arch, ventricular septal defect, and
      severe subaortic stenosis.
AB  - Interrupted aortic arch with ventricular septal defect in the neonate is
      sometimes complicated by severe subaortic stenosis from posterior deviation of
      the infundibular septum. We have developed a novel approach to the treatment of
      this condition. The infundibular septum is penetrated from the right-ventricular
      side to the left-ventricular outflow tract. It is compressed with patch fixation.
      The lower margin of the infundibular septum is everted. Three consecutive
      neonates were treated. The smallest diameters of the left-ventricular outflow
      tract were 3,4, and 2.5 mm. All patients survived the operation and were
      discharged from the hospital. They remained well 2 to 7 years after the repair
      and were in normal sinus rhythm without a left bundle branch block or any
      significant pressure gradient between the upper and lower extremities. Follow-up
      two-dimensional and Doppler echocardiography demonstrated no residual shunt, no
      left-ventricular outflow-tract pressure gradient, and no aortic regurgitation.
      This technique provides effective widening of the left-ventricular outflow tract,
      and is more safely and easily performed than conventional methods.

PMID- 9554047
TI  - Morbidity after transsternal thymectomy for myasthenia gravis: a changing
      perspective?
AB  - A detailed assessment of recent changes in morbidity and mortality after
      transsternal thymectomy for myasthenia gravis is pending. To this end, a
      retrospective analysis was carried out of morbidity and mortality rates in 125
      patients subjected to transsternal thymectomy for myasthenia gravis in the
      periods 1976-85 (1st decade) and 1986-95 (2nd decade). Composition of patients
      did not change much over time, except for more concomitant preoperative disease
      in the second decade (p = 0.001). None the less, complication rates were not
      higher, nor did the pattern of complications alter. Mortality was nil in both
      decades. There was no difference over the decades as to length of ventilation,
      intensive care treatment, or overall hospitalization. Most complications did not
      reveal a monocausal relationship, suggesting that a combination of risk factors
      was implicated. Further reductions in future morbidity rates after transsternal
      thymectomy for myasthenia gravis seem unlikely as patient preoperative state is
      unlikely to improve. In the light of the deteriorating preoperative patient
      condition, constant postoperative morbidity rates indicate that patient care has
      in fact improved.

PMID- 9554048
TI  - 'No touch' technique for coronary anastomoses with arterial grafts.
AB  - We describe a simple no-touch technique for facilitating coronary anastomosis
      using different arterial grafts. To accomplish this technique it is necessary to
      make a cut near the end of the graft creating a "cuff". Holding this cuff during
      the anastomosis steadies the graft, which simplifies the suturing technique and
      facilitates precise anastomosis.

PMID- 9554049
TI  - Preoperative estimation of resectable trachea by the cervical approach in surgery
      for tracheal stenosis.

PMID- 9554050
TI  - Pulmonary artery trunk leiomyosarcoma.
AB  - Pulmonary artery leiomyosarcomas are rare tumors. They cause symptoms suggestive
      of recurrent pulmonary emboli. As in the case reported here, the diagnosis is
      virtually never considered initially, despite modern diagnostic imaging methods,
      but usually made at autopsy or at histologic examination of material removed from
      the pulmonary artery at surgery. The prognosis remains poor and prolongation of
      life up to 6 months has not been clearly demonstrated with radical excision in
      conjunction with radiotherapy. The difficulty is the accurate diagnosis required
      to consider these tumors for curative resection, which is the only hope for a
      longer disease-free course.

PMID- 9554051
TI  - Video-assisted thoracoscopy in single-stage resection of a para-aortic posterior
      mediastinal dumbbell tumor.
AB  - We report the successful single-stage thoracoscopic resection of a neurogenic
      mediastinal dumbbell tumor close to the aortic arch, using a combined posterior
      approach. A 63-year-old asymptomatic male was referred to our hospital for
      evaluation of an abnormal round shadow in the left thoracic cavity on a chest
      radiograph. He was diagnosed to have an intrathoracic and intraspinal neurogenic
      dumbbell-shaped tumor close to the aortic arch. Surgery combined both a
      laminectomy and thoracoscopic tumor resection. The tumor was lysed as deeply as
      possible via a posterior approach, then with the patient in the right lateral
      position the pleura around the tumor on the aortic side was clipped and
      cauterized thorocoscopically, freeing the tumor completely and allowing it to be
      extracted in toto.

PMID- 9554053
TI  - Video-assisted thoracoscopic surgery in the management of acute purulent
      mediastinitis and pleural empyema.
AB  - Management of acute purulent mediastinitis requires broad-spectrum antibiotics
      and proper surgical drainage-routine use of thoracotomy is recommended by several
      authors. We describe two cases where video-assisted thoracoscopic surgery (VATS)
      was used instead of thoracotomy. Etiology of mediastinitis in one patient was a
      stab wound and in the other an iatrogenic esophageal perforation. In addition,
      the first patient had purulent pericarditis and suppurated haemothorax and the
      second a pleural empyema. In both cases VATS allowed debridement of the entire
      thoracic cavity and subsequent drainage of the mediastinum. Continuous irrigation
      was used postoperatively until pleural fluid became clear. Both patients
      recovered without a need for further surgical treatment. They are doing well 8
      and 9 months later. Adequate debridement and drainage of pleural empyema and
      mediastinitis can be achieved using VATS instead of a thoracotomy approach.

PMID- 9554052
TI  - Coronary artery bypass grafting by median sternotomy in patients with a
      tracheostoma.
AB  - The approach to the heart for open heart surgery in patients with a tracheostoma
      requires careful consideration. The presence of a tracheostoma interferes with
      the standard sternotomy and increases the risk of mediastinitis. We have
      successfully performed coronary artery bypass grafting in two patients with a
      tracheostoma using the limited median sternotomy and describe the surgical
      procedure used in these patients.

PMID- 9554054
TI  - Complete intercostal artery reimplantation using a method of aneurysmoplasty.
AB  - We report the case of a 58-year-old woman who underwent repair of a chronic
      dissecting thoracoabdominal aortic aneurysm. Using a method of aneurysmoplasty
      under normothermic cardiopulmonary bypass, all intercostal arteries were quickly
      reperfused, and the spinal cord ischemic time was minimized. No neurological
      deficits developed in our patient using this method.

PMID- 9554055
TI  - The skin sensitization potential of four alkylalkanolamines.
AB  - The skin sensitization potential of 4 alkylalkanolamines (N-methylethanolamine,
      N,N-dimethylethanolamine, N-methyldiethanolamine and N,N-diethylethanolamine),
      was evaluated in a guinea pig maximation procedure by the method of Magnusson and
      Kligman. While all 4 alkylalkanolamines tested were irritating to the guinea pig
      skin, only N-methylethanolamine showed potential to induce allergic contact
      dermatitis. None of the remaining 3 alkylalkanolamines exhibited clear skin
      responses suggestive of sensitization.

PMID- 9554056
TI  - Toxicity of Rhazya stricta to sheep.
AB  - The toxicity of Rhazya stricta leaves for Najdi sheep is described in 9 sheep
      assigned as untreated controls, Rhazya-treated at 0.25 g/kg/d and Rhazya-treated
      at 1 g/kg/d. The oral use of 1 g/kg/d caused body weight depression, ruminal
      bloat, diarrhea, dyspnea and weakness of the hind limbs. Enterohepatonephropathy,
      pulmonary congestion, hemorrhage and emphysema, lymphocytes in vital organs, and
      congestion of the blood vessels of the heart were associated with increases in
      serum AST and LDH, in elevated bilirubin and urea concentrations, and decreased
      total protein, albumin and calcium concentrations, and leucopenia and anemia.

PMID- 9554057
TI  - Cytochrome P450 enzyme activities in the Australian brushtail possum trichosurus
      vulpesula: a comparison with the rat, rabbit, sheep and chicken.
AB  - A comparative study of cytochrome P450 phase 1 biotransformation enzyme
      activities of the Australian brushtail possum was conducted. Since its
      introduction to New Zealand this animal pest has caused considerable agricultural
      and ecological problems. The objective of this work was to probe for potential
      biochemical weaknesses that may be exploited for designing a more species
      specific method of toxicological control of the possum population in New Zealand.
      Liver microsomal enzyme content and the kinetics of in vitro biotransformation
      reactions in the possum were quantified and compared with those of the rabbit,
      rat, chicken and sheep. Significant (p > 0.05) species variations in the liver
      cytochrome P450 enzyme content were observed. All mammals, including the possum,
      had considerably higher cytochrome P450, cytochrome b5 and cytochrome reductase
      levels than the chicken. The chicken had the highest specific phase 1
      biotransformation activity (Vmax) for all except 1 of the 8 xenobiotics tested.
      Among the mammals studied, P450 (Vmax) values in the possum were similar or
      higher than in the rabbit, rat or sheep. The Km values varied significantly (p >
      0.05) between species. The Km for 7-hydroxylation of coumarin was highest in the
      rat. In comparison with other species, the possum had a lower Km for aromatic
      hydroxylation of aniline, N-demethylation of N,N-dimethyl aniline, and N-dimethyl
      aniline, but a higher Km for 0-demethylation of 7-methoxycoumarin, 7
      hydroxylation of coumarin, and 0-deethylation of acetophenetidin. It was
      concluded that phase 1 biotransformation of xenobiotics in the possum is similar
      to or more efficient than in the other animals tested.

PMID- 9554058
TI  - Effect of combined fenthion and cimetidine use in rats on lethality, blood
      cholinesterase activities, and serum cholinesterase isoenzymes.
AB  - H2-receptor antagonists inhibit cholinesterase (ChE) activity. We examined
      perturbations in ChE isoenzyme patterns and ChE activities of rats from the
      combined effects of fenthion (FEN) and cimetidine (CIM). Sixty-four female
      Sprague-Dawley rats were divided into 8 groups. Four rat groups were given FEN or
      gum arabic solution and each group divided into 2 small groups according to the
      CIM or gum arabic administration. FEN was administered po at 12.3 mg/kg (1/20
      LD50) or 24.5 mg/kg (1/10 LD50) for 14 days or 49 mg/kg (1/5 LD50) every 4 days.
      CIM was given po at 1,500 mg/kg from days 7 to 13. Samples were collected 3 h
      after CIM administration on days 8 and 13. CIM did not influence ChE isoenzyme
      patterns or ChE activity. FEN inhibited both the ChE isoenzyme patterns and ChE
      activities without producing clinical signs. Although 1 rat in the 12.5 mg FEN/kg
      + CIM group died on day 10, all rats in other FEN (24.5 mg/kg or 49 mg/kg) + CIM
      groups died on days 8-10. Differences in suppression of ChE isoenzyme patterns
      were detectable between the FEN-dosed and FEN + CIM-dosed groups. There were no
      differences in ChE activities between the FEN-dosed and FEN + CIM-dosed groups.
      The i.p. administration of 500 mg CIM/kg (LD50) did not suppress ChE activities.

PMID- 9554059
TI  - Effects of phorbol esters in carp (Cyprinus carpio L).
AB  - Carp (Cyprinus carpio L) were fed diets containing phorbol esters at
      concentrations of 0, 3.75, 7.5, 15, 31, 62.5, 125, 250, 500 and 1,000
      micrograms/g feed. Phorbol esters were from Jatropha curcas nuts. Jatropha curcas
      toxicity has been reported in humans, rodents and livestock, and phorbol esters
      have been identified as the main toxic agent. The adverse effects observed in
      carp at phorbol esters concentrations of 31 micrograms/g or higher were lower
      average metabolic growth rate, fecal mucus production and rejection of feed.
      Average metabolic growth rates (g/kg 0.8/d) in a 7-d experimental period during
      which diets containing phorbol esters were fed to carp (values with different
      letters being significantly different) were 15.4a, 14.4a, 12.5ab, 12.4ab, 10.9b,
      3.4c, 0.2c, -3.8d, -4.9d and -5.6d, respectively, at the above mentioned
      concentrations. The values for the recovery phase of 9-d during which phorbol
      esters were not included in the diet were 16.0a, 15.6a, 14.9a, 15.6a, 5.3b, 1.6b,
      4.6bc, 6.3bc, 7.8c and 8.2c, respectively. The adverse effects of phorbol esters
      were reversible since withdrawal of the esters from the diets led to gain in body
      mass. None of the fish died at any of the concentrations studied. Incorporation
      of vitamin C, an antioxidant, at levels of 0.4 and 2% in the feed did not prevent
      occurrence of the adverse effects of the phorbol esters. The threshold level at
      which phorbol esters appeared to cause adverse effects in carp was 15
      micrograms/g feed or 15 ppm in the diet. Carp were highly sensitive to phorbol
      esters, thus making them a useful species for bioassay of these compounds. This
      bioassay together with other analytic procedures could be of immense use in the
      development of detoxification processes for agro-industrial products containing
      phorbol esters, such as jatropha meal or jatropha oil, and as a quality control
      method to monitor successive stages in industrial detoxification processes.

PMID- 9554061
TI  - A report of pediatric SUCCIMER overdose.
AB  - A 3-y-old child ingested SUCCIMER capsules to receive a dose of 185 mg
      dimercaptosuccinic acid/kg body weight. No adverse effects occurred.

PMID- 9554060
TI  - Sulfhemoglobinemia after dermal application of DMSO.
AB  - A 43-y-old Caucasian female applied 4 ounces of dimethyl sulfoxide (DMSO) to her
      lower abdomen for treatment of interstitial cystitis. Within 24 h she developed
      fatigue, cyanosis and dyspnea with mild exertion. She sought medical attention 10
      d later, at which time initial laboratory tests revealed a methemoglobin level of
      47%. Two doses of 1 mg methylene blue/kg i.v. were given without significant
      improvement in either her cyanosis or methemoglobin level. Repeat analysis the
      day following admission using an outside lab demonstrated a sulfhemoglobin level
      of 6.2% and a methemoglobin level of < 0.1%. No prior reports have associated
      sulfhemoglobin formation with DMSO application. Carbon monoxide-oximetry may
      falsely identify sulfhemoglobin as methemoglobin; sulfhemoglobinemia should be
      considered in cases of methemoglobinemia refractory to methylene blue therapy.

PMID- 9554062
TI  - Lead toxicity in humans from contaminated flour in Albania.
AB  - In April 1997, a severe lead poisoning in humans was reported in rural Albania
      and a 30-y-old male and a 17-y-old female died. Twenty-three persons exhibiting
      signs of lead intoxication recovered following intensive EDTA-Ca chelation
      therapy. The poisoning resulted from lead contaminated flour originating from
      repair of a mill's cracked grindstone with metallic lead. Lead levels in flour
      samples averaged 325 +/- 18 ppm and in bran were 370 +/- 22 ppm. Blood lead
      levels in intoxicated individuals averaged 0.42 +/- 0.05 ppm and were compatible
      with their symptomatic status. Contaminated bran from the same mill was fed to
      lactating cows as well. Lead levels in blood and milk of exposed cows averaged
      0.27 +/- 0.06 and 0.61 +/- 0.04 ppm, respectively.

PMID- 9554063
TI  - Calcium oxalate is the main toxic component in clinical presentations of alocasis
      macrorrhiza (L) Schott and Endl poisonings.
AB  - Alocasia macrorrhiza (L) Schott and Endl is called Hai Yu, Tien Ho, Shan Yu, Kuan
      Yin Lien, Tu Chiao lien, Lao Hu Yu and Lang Du in Chinese. Its common English
      name is Giant Elephant's Ear. The toxic effects of A macrorrhiza arise from
      sapotoxin and include gastroenteritis and paralysis of the nerve centers. From
      1985 to 1993 all individuals who called the Poison Control Center asking for
      information regarding macrorrhiza were included in this retrospective study. A
      questionnaire filled out by the Poison Control Center staff collected the
      demographic data of the victim, the reason for consumption, the prescribed part,
      clinical symptoms and signs of the victim, and medical outcome of poisonings.
      Among 27 cases of A macrorrhiza poisoning, the age was 1.5 to 68 y with 12
      females and 15 males. One had skin contact and 1 had eye contact. In the 25 cases
      that consumed the plant leaf or tuber either raw or cooked, the primary symptom
      was in injected sore throat and the secondary symptom was numbness of the oral
      cavity. Some patients had salivation, dysphonia, abdominal pain, ulcers of the
      oral cavity, difficulty in swallowing, thoracodynia, chest tightness and swollen
      lips. We believe the presence of sapotoxin alone is not sufficient to explain the
      injected swollen and ulcerative lesions. Calcium oxalate is reported distributed
      in the entire plant and results in inflammation of the oral cavity and mucous
      membranes just as our patients had.

PMID- 9554064
TI  - Putaminal infarct in methanol intoxication: case report and role of brain imaging
      studies.
AB  - Methanol toxicity can cause severe central nervous system insult in which a
      characteristic pattern of bilateral putaminal injury is noted on brain imaging
      studies. We present a fatal case of subacute methanol toxicity with associated
      diffuse brain involvement, including bilateral putaminal necrosis and cerebral
      edema with ventricular compression. Theoretical basal ganglia toxicologic
      mechanisms of methanol poisoning are reviewed, and the role of brain imaging
      studies will regard to diagnosis, prognosis and impact on management is
      discussed.

PMID- 9554065
TI  - Copper toxicosis in sheep: a case report.
AB  - Two ewes died after being fed rabbit ration and mineral salts designated for
      cows. This food is known to contain copper levels above that indicated for sheep.
      Blood counts revealed anemia, and serological tests showed high blood urea
      nitrogen, glutamic pyruvic transaminase and glutamic oxalacetic transaminase
      values. At necropsy, the animals had hepatopathy and nephropathy. Hepatic copper
      levels were 414 ppm. Histological examination revealed chronic active hepatitis
      with bile casts and tubular nephrosis. The liver, spleen and kidneys had
      hemosiderosis. This was attributed to the massive hemolysis caused by the copper.
      The liver failure and hemolytic anemia caused death in these sheep.

PMID- 9554066
TI  - Those pesky berries ... are they a source of concern?
AB  - Plant exposures constitute the 4th most common call to poison information
      centers. Within the plant category, exposures to unidentified berries are common
      and often create panic in the public and indecisiveness by health professionals.
      Are exposures to unidentified berries associated with morbidity and mortality?
      Can these berry exposures be managed at home or do they necessitate medical
      evaluation? The AAPCC Toxic Exposure Surveillance System was queried to identify
      exposures with the "unidentified berry" code for a 10-y period. Data parameters
      included frequency, age, outcome, patient disposition, referral pattern, symptom
      progression and therapeutic intervention. The data were analyzed using
      descriptive statistics. Unidentified berry exposures included 11,237 incidents,
      making it the 11th most common plant-related exposure. Children < 6 y-of-age
      accounted for 88.5% of the exposures, and 88.5% occurred during June-October.
      There were no fatalities, and morbidity included 1 major outcome in an infant and
      26 exposures with moderate outcomes. In exposures with a known outcome, no
      effects (86.0%) and minor effects (13.6%) accounted for 99.6% of exposures. When
      a patient was initially asymptomatic, 89.7% did not develop symptoms and 10.2%
      progressed to have minor symptoms, accounting for 99.9% of all exposures. Poison
      centers referred 7.5% to a health care facility. There was no apparent benefit
      conferred by decontamination therapy. Exposures to unidentified berries represent
      common inquiries to poison information centers. They are associated with low
      morbidity and no mortality. If no initial symptoms are present, it is unlikely
      that the patient will develop clinically relevant effects.

PMID- 9554067
TI  - Accidental ingestion of sustained release calcium channel blockers in children.
AB  - We examined the effects of small ingestions of sustained release calcium channel
      blockers (SR-CCBs) in young children and characterized current recommendations
      regarding monitoring after a suspected ingestion. A 2-part study was performed of
      pediatric calcium channel blocker (CCB) ingestion: first a telephone survey of 33
      randomly selected Poison Control Centers (PCCs) from around the US concerning
      their recommended management of a small ingestion of sustained release calcium
      channel blocker in a child, and then a 5-y retrospective review of local cases of
      CCB ingestions in children under 4 y-of-age. The number of hours of medical
      observation recommended by the PCCs varied from > or = 24 h (n = 15, 45%) to < 6
      h (n = 6, 18%). The retrospective chart review revealed that 19 of 29 local cases
      involved a SR-CCB, and 6 of these were thought to have ingested only 1 tablet.
      Observation time varied from > 24 h to < 6 h in the 17 cases seen in an emergency
      department. No symptoms or vital sign abnormalities were reported in any case.
      Recommendations regarding duration of observation varied from < 6 h to 24 h.
      Ingestion of a few SR-CCB tablets was not associated with symptoms, suggesting
      that admission and 24-h monitoring may not be necessary under those
      circumstances.

PMID- 9554068
TI  - "Acute poisonings due to alkalies used during industrial cleaning of soft drinks'
      glass containers: a case report".

PMID- 9554070
TI  - Human cryptosporidiosis: epidemiology, transmission, clinical disease, treatment,
      and diagnosis.
AB  - Cryptosporidiosis is now recognized as one of the most common human enteric
      infections. In this critical review, relatively unexplored details of
      transmission, the interaction with malnutrition and the development of chronic
      diarrhea, and the need for effective treatment are highlighted. Our inability to
      detect small numbers of foodborne oocysts limits our understanding of this
      transmission route, and the possibility of respiratory transmission is yet to be
      rigorously studied. The toll this disease imposes on children, especially the
      malnourished, has not been fully appreciated. Indeed, the dynamics of the
      progression from acute cryptosporidiosis to chronic diarrhea and death of
      malnourished children is still enigmatic. Our knowledge of the intestinal
      pathophysiology, while limited, is increasing. The lack of effective drug therapy
      is both remarkable and sobering. Overall, these unknown areas demonstrate how
      little we truly know about this parasite.

PMID- 9554069
TI  - Natural history and biology of Cryptosporidium parvum.
AB  - The taxonomy of the genus Cryptosporidium remains ambiguous, because the current
      criteria for speciation are insufficient to validate the 6-8 named species. Cross
      transmission experiments have shown varying and conflicting results, and the
      limited genetic data available do not necessarily support currently proposed
      species designations. The reasons for this ambiguity lie with the ubiquitous
      nature of Cryptosporidium, probably infecting all vertebrates and variety of
      tissues therein, and the absence of reference strains with defined virulence
      attributes that can be linked to genetic markers for comparative analysis. The
      inability to classify oocysts or confidently to identify their origin, implicate
      oocysts from all sources as hazardous to humans. Another major issue is the
      unusual degree of resistance that Cryptosporidium has shown to antiprotozoan and
      antimicrobial agents. The intracellular but extracytoplasmic domain the parasite
      occupies is in itself a significant barrier to drug entry. In support of this we
      outline how the intracellular niche of this parasite differs from the related
      Apicomplexans, Plasmodium and Toxoplasma, and delineate why the feeder organelle
      membrane, rather than, or in addition to, the parasitophorous membrane, is the
      major portal of nutrient entry for Cryptosporidium. The broad conclusion is that
      anticryptosporidial agents will have to enter the parasite via the multiple
      apical membranes that camouflage the parasite, or via the host cell, possibly
      transported by vesicles to the feeder organelle membrane. This may have major
      implications for rational drug discovery and design.

PMID- 9554071
TI  - Innate and cell-mediated immune responses to Cryptosporidium parvum.
AB  - Cryptosporidium parvum has gained much attention as a major cause of diarrhea in
      the world. Knowledge of the host immune mechanisms responsible for the clearance
      of this parasite from the gastrointestinal tract may prove to be vital for
      successful therapeutic treatment of cryptosporidiosis, particularly in the
      immunodeficient host. This chapter focuses on the innate and cell-mediated immune
      mechanisms associated with resistance to and resolution of a C. parvum infection.
      Much of the work in these areas is still in its infancy. Despite this, general
      consensus supports a role for interferon-gamma (IFN gamma) in mediating the
      initial resistance to C. parvum, although the mechanism by which this cytokine
      imparts resistance is unclear. It is also generally agreed that CD4+ T
      lymphocytes are required for the resolution of both acute and chronic
      cryptosporidiosis. However, the effector mechanism is again unclear. Several
      studies suggest that IFN gamma may also be involved in the resolution of
      cryptosporidiosis. However, the extent to which this cytokine is involved in the
      actual resolution of infection has been debated. Less extensive studies
      investigating the participation of other cells and cytokines in the innate and
      cell-mediated immune responses to C. parvum are also discussed.

PMID- 9554072
TI  - Antibody-based immunotherapy of cryptosporidiosis.
AB  - Passive antibody immunotherapy (PAI) for cryptosporidiosis is a treatment
      strategy that has been actively pursued in laboratory studies and early-stage
      clinical studies for the last decade. Several experimental approaches have been
      initiated, including use of bovine colostrum and colostral antibodies
      (hyperimmune and natural), monoclonal antibodies, chicken egg yolk antibodies,
      and even orally administered human plasma antibodies. Most studies have employed
      oral administration to treat or prevent this intestinal infection. The interest
      in this treatment strategy has been sparked by the lack of an effective or
      approved therapy, increased awareness of the widespread nature of this parasite,
      epidemiological evidence that humoral immunity plays an important role in host
      resistance, and several early case reports of antibody therapy in which
      remarkable resolution of the disease was observed. Most studies using a variety
      of preparations of antibodies administered to animals and humans have shown some
      degree of efficacy, though the responses have been, for the most part, partial
      rather than complete resolution of the disease. This chapter examines critically
      the scientific rationale and the evidence for PAI for cryptosporidiosis,
      including practical considerations and future approaches.

PMID- 9554073
TI  - Cryptosporidium: molecular basis of host-parasite interaction.
AB  - Host-parasite interactions occur at a number of stages during the process of
      infection with Cryptosporidium. Until recently, very little was known about the
      molecular basis of these interactions or of specific parasite and host molecules
      involved in them. Within the past decade significant advances have been made in
      our understanding of Cryptosporidium host-parasite interactions and in
      identifying molecules involved in them. However, with most interactions the story
      is far from complete and a number of gaps remain to be filled. This chapter
      reviews the existing knowledge of the molecular basis of various host-parasite
      interactions and of specific molecules that may be involved in them, and
      identifies areas in which further investigation is necessary. Identification of
      these molecules and elucidation of molecular mechanisms underlying the host
      parasite interaction are of vital importance in developing strategies to combat
      cryptosporidiosis by targeted chemo- and immunotherapy.

PMID- 9554075
TI  - Genetic heterogeneity and PCR detection of Cryptosporidium parvum.
AB  - A variety of methods have been applied to the study of genotypic and phenotypic
      polymorphism in Cryptosporidium parvum. Results from these studies have
      consistently shown the existence of different genotypes and phenotypes within the
      species. A long-term goal of this work is the identification of markers for
      virulence in humans and animals and the elucidation of transmission cycles of C.
      parvum. Achievement of these goals will depend on the identification of highly
      polymorphic loci. Of particular interest are polymorphisms amenable to typing by
      polymerase chain reaction (PCR), as C. parvum cannot be expanded in vitro.
      Fingerprinting of isolates by restriction of PCR fragments or allele-specific PCR
      has given promising results. As originally observed by isoenzyme analysis,
      genetic fingerprinting has confirmed the occurrence in humans of unique C. parvum
      genotypes which are not found among calf isolates. This observation remains to be
      reconciled with the cross-infectivity of C. parvum to ruminant and nonruminant
      hosts and the important role that bovines play in the epidemiology of C. parvum
      and human cryptosporidiosis. Although PCR detection of C. parvum DNA from
      individual oocysts has been reported, the sensitivity of PCR detection when
      working with environmental or fecal samples is significantly reduced. Therefore,
      PCR is currently not used for routine diagnosis or environmental monitoring for
      C. parvum. Inhibitors present in environmental samples, mainly in water and soil,
      which can negatively affect PCR recoveries, have been identified, and several
      methods have been proposed to circumvent these problems. The further refinement
      of detection and genetic fingerprinting protocols will provide essential tools
      for indentifying environmental sources of oocysts and elucidating transmission
      cycles.

PMID- 9554074
TI  - Cryptosporidiosis: laboratory investigations and chemotherapy.
AB  - Much progress has been achieved in the last decade in terms of development of
      laboratory techniques, reagents and in vivo models. They have undoubtedly
      contributed to better and more accurate investigations. Despite a concerted
      effort by many investigators, however, breakthroughs have been minimal. The
      development of adequate in vitro and in vivo techniques for drug screening, and
      the intensified and systematic screening, has so far not resulted in the
      discovery of an effective therapy. The reason for the failure may well be due to
      the unique biological niche the parasite occupies (discussed at length in the
      first chapter in this volume). Its location beneath the cell membrane, but
      outside the cell cytoplasm, may prove a crucial element that needs to be
      considered when designing new therapeutic approaches. Laboratory investigations
      on two drugs currently used against chronic Cryptosporidium parvum in acquired
      immune deficiency syndrome (AIDS) are discussed. This chapter also provides
      information and the rationale for work in progress in our laboratory that relates
      to the development of novel approaches for control of the disease. This includes
      the identification of molecular targets of parasite origin for drug design, and
      studies on the structure-activity relationships of partially effective drugs with
      a view to synthesize more effective derivatives. Other investigations attempt to
      establish the role of secretory antibody, and the merit of repeated mucosal
      immunizations as a means of providing protection to individuals with AIDS who are
      at risk of developing chronic C. parvum infection.

PMID- 9554076
TI  - Water-borne cryptosporidiosis: detection methods and treatment options.
AB  - Since the infamous outbreak in Milwaukee, WI, USA, of water-borne
      cryptosporidiosis affecting over 400,000 people, there have been at least 20
      smaller outbreaks associated with this parasite in the UK and North America.
      These events have led to an explosion of interest in and research on the nature
      of cryptosporidiosis as a dangerous water-borne pathogen, particularly patients
      with acquired immune deficiency syndrome (AIDS). In addition, several major
      environmental laws and proposed regulations specifically address the control of
      this parasite. The possible ramifications of these laws include billions of
      dollars of modifications to water-treatment facilities in the USA. Unfortunately,
      the methods used to gather the information on which these laws are based have
      serious deficiencies that could lead to gross underestimation of the magnitude of
      this problem. The present review considers gaps in our understanding of water
      borne cryptosporidiosis, new methods under investigation that could improve our
      ability to monitor water for the presence of this organism, and treatment and
      control strategies to limit the threat to our water supplies.

PMID- 9554077
TI  - Biology of microsporidian species infecting mammals.
AB  - Microsporidia (phylum Microspora) are obligate intracellular protozoan parasites
      that infect a wide range of vertebrate and invertebrate hosts. Over 1000 species
      have been classified into approximately 100 genera, and at least 13 species have
      been reported to infect mammals. Phylogenetically, the microsporidia are early
      eukaryotes because they have a true nucleus, possess prokaryote-like ribosomes,
      and lack mitochondria. The species that infect mammals are relatively small,
      measuring 2.0-7.0 microns long and 1.5-5.0 microns wide. The mature organism is
      the spore, which is enclosed by a chitinous coat, making it relatively resistant
      to the environment. Infections often occur by fecal-oral or urinary-oral
      transmission, although vertical transmission is quite common in the carnivores.
      Host cells become infected through a process of germination in which the spore
      propels its contents through the everting and unwinding polar filament into the
      host cell. The polar filament is unique to the microsporidia. With a few
      exceptions, microsporidiosis is typically chronic and subclinical in
      immunologically competent hosts. Young carnivores infected with microsporidia,
      however, develop severe and sometimes lethal renal disease, and immunodeficient
      laboratory animals (e.g. athymic and SCID mice) develop ascites and die from
      microsporidiosis. This review describes the morphology, life cycle, taxonomy, and
      host-parasite relationships of the species of microsporidia that infect mammals.

PMID- 9554078
TI  - Clinical syndromes associated with microsporidiosis.
AB  - Microsporidia are ubiquitous in nature. Several clinical syndromes have been
      associated with microsporidiosis, especially in HIV-infected individuals, and
      include enteropathy, keratoconjunctivitis, sinusitis, tracheobronchitis,
      encephalitis, interstitial nephritis, hepatitis, cholecystitis, osteomyelitis,
      and myositis. Diarrhea and malabsorption are the most common clinical problems.
      Enterocytozoon bieneusi is the most common microsporidial cause of intestinal
      disease. A second species, Encephalitozoon intestinalis (originally named Septata
      intestinalis) is associated with disseminated as well as intestinal disease.
      Microsporidiosis has been seen worldwide, and is recognized as a frequent enteric
      infection in patients with AIDS. The pathogenesis of intestinal disease is
      related to excess death of enterocytes as a result of cellular infection.
      Clinically, microsporidiosis most often presents with diarrhea and weight loss as
      a result of small intestinal injury and malabsorption. However, microsporidia
      have been detected in virtually all organs, and may provoke symptoms related to
      their specific localization. The diagnosis of microsporidiosis is made
      histologically, either from tissue biopsies or secretions. While transmission
      electron microscopy was required for diagnosis in the past, special stains and
      light microscopy, as well as immunohistochemical and molecular techniques are
      capable of providing a firm diagnosis. Therapeutic options are limited. Enc.
      intestinalis responds well to albendazole, while no antiparasitic therapy has
      documented efficacy in Ent. bieneusi infections.

PMID- 9554079
TI  - Microsporidiosis: molecular and diagnostic aspects.
AB  - The term 'microsporidia' is a nontaxonomic designation which is used to refer to
      a group of intracellular parasites belonging to the phylum Microspora. These
      eukaryotic obligate intracellular protozoans have been described infecting every
      major animal group, especially insects, fish and mammals. They are important
      agricultural parasites in commercially important insects, fish, laboratory
      rodents, rabbits, fur-bearing animals, and primates. There is now an increasing
      recognition of microsporidia as important opportunistic pathogens in persons
      infected with the human immunodeficiency virus (HIV). Microsporidia possess
      ribosomes with features resembling prokaryotes. Phylogenetic analysis of the rRNA
      sequence from several of the microsporidia suggests that these organisms were
      early branches in the eukaryotic evolutionary line. The data on these molecular
      phylogenetic relationships are reviewed in this paper. Inroads have recently been
      made into the molecular biology of these organisms and these data are also
      presented. Diagnosis of microsporidia infection from stool examination is
      possible and has replaced biopsy as the initial diagnostic procedure in many
      laboratories. These staining techniques can be difficult, however, due to the
      small size of the spores. The specific identification of microsporidian species
      has classically depended on ultrastructural examination. With the cloning of the
      rRNA genes from the human pathogenic microsporidia it has been possible to apply
      polymerase chain reaction (PCR) techniques for the diagnosis of microsporidial
      infection at the species level. Both staining and PCR techniques for the
      diagnosis of microsporidia are reviewed.

PMID- 9554080
TI  - Cyclospora cayetanensis.
AB  - Cyclospora cayetanensis is a coccidian pathogen in humans. Cyclosporiasis is
      characterized by mild to severe nausea, anorexia, abdominal cramping, and watery
      diarrhea. Cyclospora has now been described from patients with protracted
      diarrheal illness in North, Central and South America, the Caribbean, Africa,
      Bangladesh, south-east Asia, Australia, England, and eastern Europe, and is
      characterized by marked seasonality. Routes of transmission are still unknown,
      although the fecal-oral route, either directly or via water, is probably the
      major one. A recent outbreak in the USA suggested transmission of Cyclospora by
      ingestion of contaminated berries. Cyclospora oocysts can be detected by phase
      contrast microscopy, modified acid-fast staining, autofluorescence, and
      amplification by the polymerase chain reaction. Oocysts are not sporulated when
      excreted in the feces, and sporulated oocysts are needed for infection. Each
      sporulated oocyst contains two sporocysts and each sporocyst contains two
      sporozoites. Humans seem to be the only host for this parasite. Histopathological
      examination of jejunal biopsies from infected individuals showed mild to moderate
      acute inflammation of the lamina propria and surface epithelial disarray.
      Parasitophorous vacuoles containing sexual and asexual forms of Cycl.
      cayetanensis were located in the cytoplasm of epithelial cells. Cyclospora
      infections can be treated successfully with trimethoprim-sulfamethoxazole.

PMID- 9554083
TI  - Saccharification and alcohol fermentation in starch solution of steam-exploded
      potato.
AB  - Steam explosion pretreatment of potato for the efficient production of alcohol
      was experimentally studied. The amount of water-soluble starch increased with the
      increase of steam pressure, but the amounts of methanol-soluble material and
      Klason lignin remained insignificant, regardless of steam pressure. The potatoes
      exploded at high pressure were hydrolyzed into a low molecular liquid starch, and
      then easily converted into ethanol by simultaneous saccharification and
      fermentation using mixed microorganisms: an amylolytic microorganism, Aspergillus
      awamori, and a fermentation microorganism, Saccharomyces cerevisiae. The maximal
      ethanol concentration was 4.2 g/L in a batch culture at 15 g/L starch
      concentration, and 3.6 g/L in a continuous culture fed the same starch
      concentration. In the fed-batch culture, the maximal ethanol concentration
      increased more than twofold, compared to the batch culture.

PMID- 9554081
TI  - Large-scale preparation of the delta10 form of staphylokinase by in vitro
      processing of recombinant staphylokinase with purified human plasminogen.
AB  - The authors have developed a rapid and convenient method for purification of a
      low molecular weight form (delta 10) of the bacterial plasminogen activator,
      staphylokinase. Recombinant staphylokinase is expressed in Escherichia coli, with
      an amino terminal extension that facilitated purification by immobilized metal
      affinity chromatography. Purified staphylokinase is treated with human
      plasminogen, and the resulting truncated form is purified using a combination of
      immobilized metal affinity chromatography and hydrophobic interaction
      chromatography. Purified protein is characterized by amino terminal sequencing
      and in vitro plasminogen activation assay.

PMID- 9554084
TI  - Generation of carbohydrate-deficient transferrin by enzymatic deglycosylation of
      human transferrin.
AB  - Carbohydrate-deficient transferrin (CDT) molecules are transferrin isoforms that
      lack one or both of the carbohydrate groups attached to a normal human
      transferrin molecule. CDT has been reported to be a sensitive and specific marker
      for diagnosing alcoholism. This report demonstrates the in vitro generation of
      CDT molecules that can potentially be used as the standard in measuring CDT
      concentrations. This was achieved by deglycosylation of human transferrin with
      the enzyme Endo-beta-N-acetylglucosaminidase F2 (Endo-F2). The enzyme was
      immobilized on sepharose beads, which were packed into a column. The
      immobilization of the enzyme not only eliminated the Endo-F2 contamination of
      CDT, but also rendered the enzyme suitable for repetitive use. In this manner, it
      was possible to obtain at least 200 mg of CDT over a period of more than 3 mo,
      without any noticeable decrease of enzyme activity, using only 3.0 micrograms of
      enzyme. This proved to be an efficient method for generating CDT.

PMID- 9554087
TI  - Performance deficits following failure: learned helplessness or self-esteem
      protection?
AB  - We report two laboratory experiments which compare two competing explanations of
      performance deficits following failure: one based on Seligman's learned
      helplessness theory (LHT), and the other, on self-esteem protection theory
      (SEPT). In both studies, participants (Study 1: N = 40 pupils from secondary
      schools in Walbrzych, Poland; Study 2: N = 45 students from the University of
      Bielefeld, Germany) were confronted with either success or failure in a first
      phase of the experiment. Then, in the second phase of the experiment the
      participants had to work on a set of mathematical problems (Study 1) or a set of
      tasks taken from Raven's Progressive Matrices (Study 2) either privately or in
      public. In both studies failure in the first phase causes performance deficits in
      the second phase only if the participants had to solve the test tasks in public.
      These results were interpreted in line with SEPT and as incompatible with LHT.

PMID- 9554086
TI  - Friends, lovers and spouses: intimacy in young adults.
AB  - Intimacy in young heterosexual adults was studied as a function of their familial
      roles. The 168 males and females employed represented four familial role groups:
      late adolescents, single adults, married people and parents. Participants were
      administered two forms of an Intimacy Scale (Sharabany, 1994) in which they
      described their desired and their obtained intimacy with a same-sex and an
      opposite-sex best friend. Results indicated that (a) intimacy of adults with
      opposite-sex partner was higher than intimacy with same-sex friend. (b) Although
      no direct effect of familial role on intimacy was found, the married and parent
      groups displayed greater intimacy towards their spouses than late adolescents and
      single adults towards their opposite-sex partners. (c) Women who were late
      adolescents and women who were married scored significantly higher than men in
      intimacy. However, single women expressed significantly lower intimacy than
      single men. (d) Higher intimacy with opposite-sex partner was associated with a
      concurrent lower same-sex intimacy. (e) Satisfaction with other-sex partner was
      higher in the married group than in the other groups.

PMID- 9554085
TI  - Some tests of the distinction between attitude and perceived behavioural control.
AB  - Although perceived behavioural control has recently become a popular variable for
      use in predicting behaviour or intention to behave, it is far from clear that
      this variable is theoretically distinguishable from attitude. Consequently, we
      performed some tests of the distinction between attitude and perceived
      behavioural control. In Expt 1, using participants from an American university,
      the semantic differential scales that have often been used to measure attitude
      and perceived behavioural control were submitted to factor analyses. Consistent
      with the distinction, a two-factor solution resulted in the attitude and
      perceived behavioural control items clearly loading on different factors.
      Further, Expt 2 demonstrated that the attitude factor predicts behavioural
      beliefs and does not predict control beliefs, but the reverse is true concerning
      the perceived behavioural control factor. Finally, in Expts 3-5, the beliefs
      presumed to underlie these two variables were cluster analysed. Consistent with
      the distinction, and paralleling findings obtained by Trafimow & Fishbein (1995),
      the order in which participants wrote down their beliefs exhibited significant
      clustering by belief type.

PMID- 9554088
TI  - Gender solidarity in hierarchical organizations.
AB  - Previous research has suggested that promotion decisions in hierarchical
      organizations may vary as a function of the decision maker's sex. In particular,
      it has been argued that women may be more likely to support a same-sex other than
      men due to higher levels of identification with their gender in-group. This paper
      reports findings from two experiments which examine gender identification and
      candidate promotion strategies amongst university students (N = 116) and public
      servants (N = 136) in hypothetical organizations which manipulated the
      participants' personal status and that of their gender in-group. In the
      university sample women did identify more strongly with their sex than men. This
      was not generally the case in the public service sample, although here women with
      high personal status tended to show greater identification than men in a similar
      position. However, in both studies there was little evidence that gender
      identification was associated with preferential treatment of in-group candidates
      in promotion-related decisions. These decisions were generally influenced by
      norms of fairness qualified by the participants' personal status. Implications
      for the self-categorization process are discussed.

PMID- 9554089
TI  - Inter-judge agreement in evaluation of adult attachment style: the impact of
      acquaintanceship.
AB  - Inter-judge agreement in the evaluation of attachment style was examined across
      different levels of acquaintanceship. A self-rating scale on attachment style was
      administered to 242 students. Then, 72 participants--25 avoidant, 25 secure, and
      22 ambivalent--were invited to the laboratory in unacquainted same-sex pairs,
      videotaped during a five-minute conversation, and asked to rate the attachment
      style of their conversion partner. In addition, each participant asked four
      friends to rate his/her attachment style and the videotaped interactions were
      shown to a separate sample of strangers who rated participants' attachment
      styles. The results showed high correlations between participants' self-reported
      attachment styles and the manner in which they were perceived by their friends
      and conversation partners. In contrast, correlations with ratings by strangers
      based on videotaped interactions were low. This pattern of findings was observed
      in both discrete and continuous measures of attachment. The findings suggest that
      attachment style can be considered an observable interpresonal trait.

PMID- 9554090
TI  - Habit versus planned behaviour: a field experiment.
AB  - A field experiment investigated the prediction and change in repeated behaviour
      in the domain of travel mode choices. Car use during seven days was predicted
      from habit strength (measured by self-reported frequency of past behaviour, as
      well as by a more covert measure based on personal scripts incorporating the
      behaviour), and antecedents of behaviour as conceptualized in the theory of
      planned behaviour (attitude, subjective norm, perceived behavioural control and
      behavioural intention). Both habit measures predicted behaviour in addition to
      intention and perceived control. Significant habit x intention interactions
      indicated that intentions were only significantly related to behaviour when habit
      was weak, whereas no intention-behaviour relation existed when habit was strong.
      During the seven-day registration of behaviour, half of the respondents were
      asked to think about the circumstances under which the behaviour was executed.
      Compared to control participants, the behaviour of experimental participants was
      more strongly related to their previously expressed intentions. However, the
      habit-behaviour relation was unaffected. The results demonstrate that, although
      external incentives may increase the enactment of intentions, habits set boundary
      conditions for the applicability of the theory of planned behaviour.

PMID- 9554091
TI  - Synchrony effects in inhibitory control over thought and action.
AB  - Two experiments explore whether synchrony between peak circadian arousal periods
      and time of testing influences inhibitory efficiency for younger and older
      adults. Experiment 1 assesses inhibitory control over no-longer-relevant
      thoughts, and Experiment 2 assesses control over unwanted but strong responses,
      as well as performance on neuropsychological tasks that index frontal function.
      Inhibitory control is greatest at optimal times for both age groups and is
      generally greater for younger than for older adults. Performance on 2
      neuropsychological measures (Stroop and Trails) also changes over the day, at
      least for older adults, and is correlated with inhibitory indexes, suggesting
      that for older adults changes in inhibition may be mediated by circadian
      variations in frontal functioning. By contrast, access to well-learned responses
      is not vulnerable to synchrony or age effects.

PMID- 9554092
TI  - Mechanisms of phonological inference in speech perception.
AB  - Cross-modal priming experiments have shown that surface variations in speech are
      perceptually tolerated as long as they occur in phonologically viable contexts.
      For example, [symbol: see text] (frayp) gains access to the mental representation
      of freight when in the context of [symbol: see text] (frayp bearer) because the
      change occurs in normal speech as a process of place assimilation. The locus of
      these effects in the perceptual system was examined. Sentences containing surface
      changes were created that either agreed with or violated assimilation rules. The
      lexical status of the assimilated word also was manipulated, contrasting lexical
      and nonlexical accounts. Two phoneme monitoring experiments showed strong effects
      of phonological viability for words, with weaker effects for nonwords. It is
      argued that the listener's percept of the form of speech is a product of a
      phonological inference process that recovers the underlying form of speech. This
      process can operate on both words and nonwords, although it interacts with the
      retrieval of lexical information.

PMID- 9554093
TI  - Figure-ground organization and object recognition processes: an interactive
      account.
AB  - Traditional bottom-up models of visual processing assume that figure-ground
      organization precedes object recognition. This assumption seems logically
      necessary: How can object recognition occur before a region is labeled as figure?
      However, some behavioral studies find that familiar regions are more likely to be
      labeled figure than less familiar regions, a problematic finding for bottom-up
      models. An interactive account is proposed in which figure-ground processes
      receive top-down input from object representations in a hierarchical system. A
      graded, interactive computational model is presented that accounts for behavioral
      results in which familiarity effects are found. The interactive model offers an
      alternative conception of visual processing to bottom-up models.

PMID- 9554094
TI  - The psychological refractory period effect following callosotomy: uncoupling of
      lateralized response codes.
AB  - A callosotomy patient was tested in 2 dual-task experiments requiring successive
      speeded responses to lateralized stimuli. The patient showed a robust
      psychological refractory period (PRP) effect. Three aspects of the data indicate
      that, unlike for the control participants, the PRP effect for the split-brain
      patient should not be attributed to a response selection bottleneck. First, the
      patient did not show an increase in reaction time (RT) when the 2 tasks required
      responses from a common output system compared with when different output systems
      were used. Second, inconsistent stimulus-response mappings for the 2 tasks
      increased RTs for the control participants but had minimal effect on the
      performance of the split-brain patient. Third, the consistency manipulation was
      underadditive with stimulus onset asynchrony but was additive or overadditive for
      the normal participants. These results suggest that the persistent PRP effect
      following callosotomy should be attributed to a bottleneck associated with
      response initiation, a strategy adopted to comply with the task demands, or a
      combination of these factors.

PMID- 9554095
TI  - Multiple-location access in vision: evidence from illusory line motion.
AB  - Four experiments with undergraduates used illusory line motion (ILM) to contrast
      Z. W. Pylyshyn's (1989) FINST theory of spatial indexing with predictions made by
      unitary attention models. Multiple-onset stimuli were able to cause ILM at
      disparate, noncontiguous spatial locations. Consistent with gradient explanations
      of ILM and with FINST theory predictions, varying line-drawing speed and the
      number of stimuli revealed a decrease in ILM and a capacity limitation,
      respectively. Modeling analyses suggested a limit in the number of locations (5
      7) that could elicit the illusion. Requiring participants to report the locations
      of all stimuli exhibiting illusory motion in a specified direction suggested
      parallel access to between 2 and 5 display locations simultaneously. The results
      of all 4 experiments were predicted by FINST theory but not by a broad class of
      unitary attention hypotheses.

PMID- 9554096
TI  - Higher order and lower order variables in the visual perception of relative
      pulling force.
AB  - In 7 experiments, undergraduates judged the force exerted by a videotaped
      standing puller, a computer-generated (stick-figure) puller, or a computer
      generated inverted pendulum. Single and stepwise multiple regression analyses
      determined the kinematic variables exploited by the participants. Results show
      that (a) judgments correlated highly with force and improved with feedback; (b)
      judgments correlated more highly with lower order kinematic variables than with
      force itself; (c) participants differed in the kinematic variables exploited; (d)
      participants changed over blocks of trials in the variables exploited; (e) some
      participants used compound kinematic variables; (f) the variables exploited
      depended on the type of feedback; and (g) judgments to upright pullers, inverted
      pullers, and simple pendula showed the same qualitative patterns. Implications
      for theories of direct perception, directed perception, and heuristics are
      considered.

PMID- 9554097
TI  - Frames of reference and control parameters in visuomanual pointing.
AB  - Three hypotheses concerning the control variables in visuomanual pointing were
      tested. Participants pointed to a visual target presented briefly in total
      darkness on the horizontal plane. The starting position of the hand alternated
      randomly among 4 points arranged as a diamond. Results show that during the
      experiment, movement drifted from hypometric to hypermetric. Final positions
      depended on the starting position. Their average pattern reproduced the diamond
      of the starting points, either in same orientation (hypometric trials), or with a
      double inversion (hypermetric trials). The distribution of variable errors was
      elliptical, with the major axis aligned with the direction of the movement.
      Statistical analysis and Monte Carlo simulations showed that the results are
      incompatible with the final point control hypothesis (A. Polit & E. Bizzi, 1979).
      Better, but not fully satisfactory, agreement was found with the view that
      pointing involves comparing initial and desired postures (J. F. Soechting & M.
      Flanders, 1989a). The hypothesis that accounted best for the results is that
      final hand position is coded as a vector represented in an extrinsic frame of
      reference centered on the hand.

PMID- 9554098
TI  - Processing of illegal consonant clusters: a case of perceptual assimilation?
AB  - Evidence is presented for a perceptual shift affecting consonant clusters that
      are phonotactically illegal, albeit pronounceable, in French. They are perceived
      as phonetically close legal clusters. Specifically, word-initial /dl/ and /tl/
      are heard as /gl/ and /kl/, respectively. In 2 phonemic gating experiments,
      participants generally judged short gates--which did not yet contain information
      about the 2nd consonant /l/--as being dental stops. However, as information for
      the /l/ became available in larger gates, a perceptual shift developed in which
      the initial stops were increasingly judged to be velars. A final phoneme
      monitoring test suggested that this kind of shift took place on-line during
      speech processing and with some extratemporal processing cost. These results
      provide evidence for the automatic integration of low-level phonetic information
      into a more abstract code determined by the native phonological system.

PMID- 9554099
TI  - Perceived orientation of axis of rotation in structure-from-motion.
AB  - Perceived orientation of axis of rotation and accuracy in discriminating fixed
      axis from nonfixed-axis rotations were investigated for orthographic projections
      of three-dimensional rotating objects. The principal findings were (a) the slant
      of the axis of rotation was systematically misperceived; (b) in both two-view and
      multiview displays, the perceived slant of the axis of rotation was well
      predicted by the ratio between the deformation (a property of the first-order
      optic flow) and the component parallel to the image plane of the global velocity
      vector; (c) if this ratio was kept constant in each frame transition of the
      stimulus sequence (or it was varied), then the stimuli tended to be judged as
      fixed-axis rotations (or as nonfixed-axis rotations), regardless of whether they
      simulated a fixed-axis rotation or not; and (d) the tilt of the axis of rotation
      was perceived in two-view displays with a very small error.

PMID- 9554100
TI  - Recognition by action: dissociating visual and semantic routes to action in
      normal observers.
AB  - In this article the operation of a direct visual route to action in response to
      objects, in addition to a semantically mediated route, is demonstrated. Four
      experiments were conducted in which participants made gesturing or naming
      responses to pictures under deadline conditions. There was a cross-over
      interaction in the number of visual errors relative to the number of semantic
      plus semantic-visual errors in the two tasks: In gesturing, compared with naming,
      participants made higher proportions of visual errors and lower proportions of
      semantic plus semantic-visual errors (Experiments 1, 3, and 4). These results
      suggest that naming and gesturing are dependent on separate information
      processing routes from stimulus to response, with gesturing dependent on a visual
      route in addition to a semantic route. Partial activation of competing responses
      from the visual information present in objects (mediated by the visual route to
      action) leads to high proportions of visual errors under deadline conditions.
      Also, visual errors do not occur when gestures are made in response to words
      under a deadline (Experiment 2), which indicates that the visual route is
      specific to seen objects.

PMID- 9554101
TI  - Investigating single-word syntactic primes in naming tasks: a recurrent network
      approach.
AB  - Three experiments compared the qualitative pattern of participants' word-naming
      performance in a syntactic priming task with the qualitative pattern of
      performance generated by a recurrent network model. Experiments 1 and 2
      demonstrated that when participants had a 600-ms response deadline, the
      appropriateness of a syntactic prime affected their naming times for high
      frequency words but not low-frequency words. However, Experiment 2 also
      demonstrated that participants made the most pronunciation errors when naming
      inconsistent low-frequency words (e.g., pint) that were preceded by an
      inappropriate prime. The results of Experiment 3 suggest that participants'
      naming times to both high- and low-frequency words are affected by syntactic
      primes when there is no response deadline. The implication of these findings for
      the study of syntactic priming in English and other languages is discussed.

PMID- 9554102
TI  - Object-based perceptual grouping affects negative priming.
AB  - In 5 experiments the authors examine the role of object-based grouping on
      negative priming. The experiments used a letter-matching task with multiple
      letters presented in temporally separated prime and probe displays. On mismatch
      trials, distractor letters in primes were repeated as targets in probes, or
      distractor and target letters were completely different. Negative priming was
      shown by slowed responses when distractors were repeated as targets relative to
      when the stimuli differed. This occurred both when only letters were presented
      (Experiments 1 and 4) and when letters were surrounded by boxes (Experiment 5).
      Experiments 2, 3, and 4 showed that negative priming was affected by the grouping
      of target and distractor letters in prime displays. Negative priming was reduced
      when 1 of the distractor letters was placed in the target box and 1 was left
      outside the box; facilitatory priming was observed when both distractor letters
      appeared in the target box. The data were accounted for in terms of there being
      (a) object-based competition for visual selection, (b) inhibition of distractor
      objects that compete for selection with target objects, and (c) activation or
      inhibition of the identities of all component elements within target or
      distractor objects.

PMID- 9554103
TI  - The contribution of covert attention to the set-size and eccentricity effects in
      visual search.
AB  - To reexamine the role of covert attention in visual search, the authors directly
      manipulated attention by peripherally cueing the target location and analyzed its
      effects on the set-size and the eccentricity effects. Observers participated in
      feature and conjunction tasks. Experiment 1 used precues, and Experiment 2 used
      postcues in a yes-no task under valid-, invalid-, and neutral-cueing conditions.
      Experiments 3 and 4 used a 2-interval alternative forced-choice visual-search
      task under cued and neutral conditions. Precueing the target location improved
      performance in feature and conjunction searches; postcueing did not. For the cued
      targets, the eccentricity effect for features and conjunctions was diminished,
      suggesting that the attentional mechanism improves the quality of the sensory
      representation of the attended location. The conjunction set-size effect was
      reduced but not eliminated. This questions serial-search models that attribute a
      major role to covert attention in visual search.

PMID- 9554104
TI  - Quantitative information of specific diagnostic tests.
AB  - The goal of diagnostic testing is to maximize information (I) of a specific
      disease of interest (D) resulting from the performance of a specific diagnostic
      test procedure (T). However, all tests suffer from errors which result in
      incomplete information and inaccurate diagnostic conclusions. The methods of
      Information Theory have successfully solved a range of signal transmission
      problems involving physical systems operating under conditions of noise. Medical
      testing procedures were found to be analogous to noisy systems; hence,
      Information Theory methods were applied to minimize errors in diagnostic testing.
      Prior to performing a diagnostic test, the quantity of information, Apriori
      Information (ID), regarding the presence or absence of the disease was only a
      function of the prevalence (P) of disease in the population. After performing a
      diagnostic test, the quantity of information, Aposteriori Information (IDIT) was
      a function of not only P but also the test sensitivity (A) and test specificity
      (B). The quantity of information gained by test performance was computed from the
      difference between aposteriori and apriori information. delta I = IDIT - ID To
      illustrate the relationship between pretest, apriori, and post-test, aposteriori,
      information the values of ID and IDIT were computed for five common
      cardiovascular tests applied to populations with different coronary artery
      disease prevalence. This cross-sectional analysis studied the quantitative
      information obtained from Electrocardiography (ECG), Bicycle Ergometer Stress
      Tests (BEST), Stress-Echo Ergometer Tests (SEET), Thallium 201 Stress Tests
      (ThST), and Coronary Arteriography (CorA). Apriori information ranged from a
      minimum of 0 (for prevalence = 0.5) to a maximum of 1.0 (for prevalence = 0 or
      1.0) The aposteriori information was computed for all apriori information and
      occupied the range between that of a "perfect" test (A = 1.0 and B = 1.0) and
      that of a "worthless" test (A = 0.5 and B = 0.5). All tests demonstrated greater
      information gain when apriori information was minimal; Little additional
      information could be gained when the apriori information was close to certainty
      (i.e., for prevalence near 0 or 1.0). Electrocardiography demonstrated little
      significant IDIT at any value of ID. Thallium 201 stress tests provided similar
      aposteriori information values to those of Stress-Echo Ergometer Stress and
      either demonstrated greater information gain than Bicycle Ergometer Stress Tests.
      Coronary Arteriography provided the maximum values of aposteriori information.
      Information Theory methods provided an effective quantitative method to compare
      the effectiveness of diagnostic tests over a wide range of disease prevalence.

PMID- 9554106
TI  - Longitudinal studies to determine the effect of body fat rate reduction on blood
      pressure.
AB  - Body constitution is estimated by weight as a quantity index and percent body fat
      (%BF) as a quality index. Obesity is one of the risk factors in hypertension.
      High blood pressure drops by body weight reduction. The relationship between %BF
      change and blood pressure change during 1 year, and whether blood pressure
      changed in subjects whose %BF decreased without body weight reduction, were
      investigated. %BF was measured with bioelectrical impedance analysis. The changes
      of body weight, %BF and blood pressure in the decreased %BF group that decreased
      more than 2 points of %BF, and in the no body weight change group which body
      weight had not changed in the decreased %BF group, were studied. In the decreased
      %BF group, average blood pressures fell significantly from 149/92 to 141/86 mm Hg
      in the subjects in hypertensive state at baseline. In the no weight change group,
      average blood pressures also fell significantly from 151/93 to 140/87 mm Hg. Even
      if the body weight had not changed, blood pressure had decreased significantly
      when %BF had decreased significantly.

PMID- 9554105
TI  - Ultrasonographically assessed carotid intima-media thickness and risk for
      asymptomatic cerebral infarction.
AB  - Cerebral infarction (CI) is still a leading cause of death in Japan. Thus, the
      management of risk factors for CI as primary prevention is one of the most
      important tasks in multiphasic health testing and services. To determine whether
      carotid intima-media thickness (IMT) is a risk for CI, ultrasonographically
      assessed carotid IMT was compared between normal subjects (N) and subjects with
      asymptomatic CI (ACI) in 243 subjects who underwent human brain dry dock. ACI was
      found in 68 people (28.0%). Age, body mass index, and mean blood pressure were
      higher in ACI than in N. Also, atherogenic index was higher in ACI than in N.
      Carotid IMT was significantly thicker in ACI than in N. Furthermore, incidence of
      atherogenic plaque in ACI was significantly higher than that in N. In conclusion,
      not only aging, obesity, blood pressure, and plasma lipids, but also carotid IMT
      may be a risk for ACI.

PMID- 9554107
TI  - Health risk assessment for diabetes mellitus based on longitudinal analysis of
      MHTS database.
AB  - This study was designed with a follow up of 16 years to provide the
      epidemiological model evaluating the risk of developing diabetes mellitus in
      Japan. A cohort of 2573 subjects (1851 males and 722 females) from a MHTS in
      Tokyo, who were nondiabetic (fasting blood glucose (FBS) less than 110 mg/dl) in
      the initial year, were selected. This cohort was followed every year to identify
      the occurrence of diabetes mellitus. Diabetes Mellitus was defined as fasting
      blood glucose over 110 mg/dl, or the initiation of diabetic therapy. We compared
      two prognosis groups (a normal group and a diabetic group) in terms of age,
      examination findings, and prevalence of health risks (lifestyle, stress, and
      working form). We also assessed family history of diabetes and past histories
      including hypertension, hypercholesterolemia, and hyperuricemia. After assessing
      each variable by univariate analysis (t-test, chi 2 test), we employed Cox's
      proportional hazards model analysis. We used stepwise model adopting risk
      factors. The diabetic group had significant differences compared to the normal
      group in age, BMI (body mass index), FBS, smoking, drinking, not eating
      breakfast, dairy intake, hypertension, hypercholesterolemia, hyperuricemia, and
      family history by univariate analysis. According to proportional hazards model
      analysis, FBS, age, family history, hypertension, smoking, and BMI were
      incorporated into significant risk factors for diabetes in males, and not eating
      breakfast, FBS, age, drinking, and hypertension were incorporated in females.
      Diabetes seemed to be related to fixed factors (age), or genetic factors (family
      history and FBS) in males. For females, lifestyle (not eating breakfast and
      drinking habit) seemed to play an important role. It will be worthwhile to assess
      the risks of developing diabetes mellitus by this epidemiological model.

PMID- 9554108
TI  - The validity of cognitive testing in screening for dementia.
AB  - The concept of "cognitive impairment," as an indicator of dementia, defined in
      1980 as a loss of intellectual abilities of sufficient severity to interfere with
      social or occupational functioning, is the model which has been adopted for a
      condition, which has recently been reclassified from an "organic" to a "cognitive
      disorder." Data derived from the assessment of a sample of older people
      demonstrated the extreme sensitivity of a widely employed cognitive assessment
      instrument to all levels of educational experience, and educational correlates,
      notably level of physical disability, were identified as other independent
      predictors of test performance. The analyses raise questions with regard to the
      reinterpretation of "lack of education," from a confounding factor in prevalence
      estimates of cognitive impairment to a "risk factor" for dementia, and support
      those who have questioned the validity of the one-dimensional "cognitive
      paradigm," and the trend to diagnosis based upon objective assessment with
      standardized instruments.

PMID- 9554109
TI  - Development of a health promotion system for the elderly: Committee of Health
      Evaluation for Elderly Persons Council of Japan AMHTS Institutions.
AB  - A new health promotion approach for elderly persons is required which maintains
      not only their physical health but also their quality of life. We are developing
      a health promotion system which makes use of questionnaires dealing with physical
      conditions and quality of life, and makes health reports. Health evaluation is
      carried out in three steps. First, detailed information about the physical health
      of each client is collected. Second, quality of life is evaluated according to
      five health indicators. Last, health recommendations are generated. An artificial
      intelligence (AI) program produces detailed questions to collect necessary
      information for the evaluation of a client's health. The information related to
      quality of life is converted into five health indicators and presented as a radar
      chart in documents and displays. The knowledge-based AI program automatically
      generates the health recommendation documents. This information is available for
      physicians and nurses for health counseling.

PMID- 9554110
TI  - Driving safe & sober.

PMID- 9554111
TI  - Fitness-for-duty testing.

PMID- 9554112
TI  - First aid: medical or safety?

PMID- 9554113
TI  - Medical miracles.

PMID- 9554114
TI  - Quantitative evaluation of protein-protein and ligand-protein equilibria of a
      large allosteric enzyme by electrospray ionization time-of-flight mass
      spectrometry.
AB  - A mass spectrometer coupling electrospray ionization with time-of-flight mass
      spectrometry (ESI-TOFMS) has been used to investigate the oligomeric species of
      Escherichia coli citrate synthase, and to determine the effect of nicotinamide
      adenine dinucleotide (NADH), an allosteric inhibitor of this enzyme, on the
      equilibrium between the oligomeric forms. An equilibrium mixture of dimers (M =
      95,770 Da) and hexamers (M = 287,310 Da) was found under the conditions used (KA
      = 6.9 x 10(10) M-2), and NADH was observed to bind selectively to the hexamer (KD
      = 1.1 microM), shifting the equilibrium to the latter form. The power of ESI
      TOFMS to measure ions of very large mass-to-charge ratio (up to m/z approximately
      10,000 in this case) is shown to be a valuable tool for obtaining accurate
      information about compositions of noncovalent complexes and equilibrium
      constants. The measured constants agree with those determined by conventional
      means.

PMID- 9554115
TI  - [Eulogy of Mr. Andre Djourno (1904-1996)].

PMID- 9554116
TI  - [Current issues in respiratory allergology].
AB  - To summarise in a few lines our present understanding of respiratory allergies
      necessarily limits the number of topics which can be addressed. The role of
      aeroallergens in these diseases, both those which were previously unknown or non
      existent and those which were well characterised (cypress, ambrosia) but which
      are becoming more prevalent in the atmosphere has now been demonstrated. The
      understanding of the mechanisms of respiratory allergies, which are essentially
      derived from tissue inflammation, has undergone rapid progress and evolved
      towards the identification of transcription factors which regulate the genes
      coding for cytokines, enzymes and adhesion molecules. Specific immunotherapy
      should be heralded as one of the key elements in the global therapeutic strategy
      for respiratory allergies as long as the indications for it are rationally
      discussed. Our increasing our knowledge of the genetics of respiratory allergies
      should continue to stimulate research projects, but the results obtained so far
      underline the complexity of this domain and diagnosis and treatment via genetics
      remains in the future.

PMID- 9554117
TI  - [New aero-allergens. Interaction between allergens and the environment].
AB  - There is a qualitative as well as a quantitative change in allergen exposure.
      From a qualitative viewpoint, the relevance of some allergens (domestic allergens
      i.e. cockroaches, outdoor allergens i.e. plane tree, chestnut and ash tree
      pollens) has been established. The role of some other allergens has been,
      strictly speaking, discovered: latex from Hevea and ficus, trichophyton mold,
      some occupational allergens and very recently transgenic allergens. From a
      quantitative viewpoint, the concentration and/or distribution of some allergens
      has increased. Plantation of numerous trees or fortuitous introduction of weeds
      has led to an increased specific sensitization. In like manner, introduction of
      new foods or food processing procedures has created new food allergens and
      allergy. Besides, the distribution of some well-known aero-allergens is better
      known since discovery of ELISA--technology allowing measurements of minute
      amounts of these allergens. A burning issue today is to know whether irritant
      factors could modify allergens. Few data, sometimes contradictory, are available
      in the field of interaction between air pollutants and allergens.

PMID- 9554118
TI  - [Recent data on the physiopathology of respiratory allergies].
AB  - Mechanisms of the allergic inflammatory reaction in the respiratory tract, such
      as those involved in chronic asthma and allergic rhinitis involve a complex and
      integrated cellular cascade. After allergen inhalation, the response is initiated
      by the airway epithelial dendritic cells which are responsible after
      transportation to regional lymph nodes, for the presentation to naive CD4+ T
      helper (Th0) cells. After the first phase of allergen sensitization, CD4+ T cells
      give rise in atopic patients to lymphocytes CD4+ with a cytokine profile of Th2
      type (secretion of IL-4, IL-5 and IL-13). Both cytokines IL-4 and IL-13 favor the
      IgE antibody production towards inhaled allergens, while IL-5 allows the
      differentiation, activation and survival of eosinophils. Among effector cells,
      two are predominant: mast-cells and activated eosinophils. During the initiation
      phase of the allergic reaction the dominant phenomena is represented by IgE
      mediated mast cell/basophil activation which leads to the release of granular
      mast cell mediators but also to the secretion by mast cells of cytokines also
      offering a Th2 profile. Moreover in chronic asthma histopathological,
      immunocytochemical studies and in situ hybridization techniques demonstrate a
      large recruitment of inflammatory cells, mainly of activated eosinophils that
      similarly produce Th2 type cytokines and participate in the development of the
      local allergic inflammation. Several additive environmental factors such as
      viruses or aeropollutants are susceptible to amplify the Th2 type response;
      conversely specific immunotherapy has been shown to allow a shift from the Th2 to
      Th1 profile, which explains at least for a part its therapeutic effects.

PMID- 9554119
TI  - [Specific immunotherapy of respiratory allergies].
AB  - Specific immunotherapy has been in routine use since 1911 for the treatment of
      respiratory allergic diseases. There is however a certain amount of controversies
      regarding its overall indications. Its efficacy has been demonstrated in double
      blind placebo controlled studies in both allergic rhinoconjunctivitis and
      allergic asthma. The improvement of allergenic extracts (in particular by
      standardization), the better understanding of the mechanisms of action of
      immunotherapy, the recently proposed use of other administration routes and the
      publication of guidelines have legitimated its definite role to play in the
      therapeutic management of allergic respiratory diseases.

PMID- 9554120
TI  - [Recent advances in the genetics of respiratory allergies].
AB  - The genetics of atopy and asthma is a fascinating area of research which has made
      tremendous progresses over the last couple of years. It has been known for ages
      that allergies and asthma are concentrating within families. Modern genetics has
      pintpointed some gene areas such as 5q31.1, 6p21.3, 11q13, 12q15 and 14q11.1. To
      do so, a crucial step is the definition of the phenotypes. Once the phenotype is
      set up (which is not an easy task), familial aggregation and segregation studies
      can be performed. These familial studies allow molecular genetics and linkage
      analysis. Both candidate gene approach and genome-wide search have been utilized
      in the genetic of atopy and asthma. Much of the information available today has
      been fragmentary and not always confirmed. Alleles at multiple loci are likely to
      be involved and the ultimate picture is most likely determined by many genetic
      and environmental factors.

PMID- 9554121
TI  - [A new concept in digestive surgery: the computer assisted surgical procedure,
      from virtual reality to telemanipulation].
AB  - Surgical simulation increasingly appears to be an essential aspect of tomorrow's
      surgery. The development of a hepatic surgery simulator is an advanced concept
      calling for a new writing system which will transform the medical world: virtual
      reality. Virtual reality extends the perception of our five senses by
      representing more than the real state of things by the means of computer sciences
      and robotics. It consists of three concepts: immersion, navigation and
      interaction. Three reasons have led us to develop this simulator: the first is to
      provide the surgeon with a comprehensive visualisation of the organ. The second
      reason is to allow for planning and surgical simulation that could be compared
      with the detailed flight-plan for a commercial jet pilot. The third lies in the
      fact that virtual reality is an integrated part of the concept of computer
      assisted surgical procedure. The project consists of a sophisticated simulator
      which has to include five requirements: visual fidelity, interactivity, physical
      properties, physiological properties, sensory input and output. In this report we
      will describe how to get a realistic 3D model of the liver from bi-dimensional 2D
      medical images for anatomical and surgical training. The introduction of a tumor
      and the consequent planning and virtual resection is also described, as are force
      feedback and real-time interaction.

PMID- 9554122
TI  - [The robotization of neurosurgery: state of the art and future outlook].
AB  - Neurosurgery is by excellence a field of application for robots, based on
      multimodal image guidance. Specific motorized tools have been already developed
      and routinely applied in stereotaxy to position a probe holder or in conventional
      neurosurgery to hold a microscope oriented towards a given target. The
      potentialities of these approaches have triggered industrial developments
      currently commercially available. These systems use data bases, primarily coming
      from multimodal numerical images from X-ray radiology to magnetic resonance
      imaging. These spatially encoded data are transferred through digital networks to
      workstations where images can be processed and surgical procedures are
      preplanned, then transferred to the robotic systems to which they are connected.
      We have been using a stereotactic robot since 1989 and a microscope robot since
      1995 in various surgical routine procedures. The future of these applications
      mainly rely on the technical progress in informatics, about image recognition to
      adapt the preplanning to the actual surgical situation, to correct brain shifts
      for instance, about image fusion, integrated knowledge such such as brain
      atlases, as well as virtual reality. The future developments, covering surgical
      procedure, research and teaching, will sure be far beyond our wildest
      expectations.

PMID- 9554123
TI  - [Vaccination against malaria. Disappointments and hopes].
AB  - After the first in vitro cultivation of Plasmodium falciparum 21 years ago, the
      prospect of anti-malarial vaccination arose many hopes, but, in the end, it so
      far has mainly given rise to doubts and disappointments. Technically, the problem
      is particularly difficult. Plasmodium falciparum has a very complex antigenic
      structure with several hundreds, if not several thousands, of different epitopes
      for each of the four main evolutive stages of the parasite (sporozoites,
      merozoites, gametocytes, ookinetes) which correspond to different phase of the
      infection and could be a target for vaccination. Many of these epitopes are stage
      specific and some of them vary from one strain to another. Adjuvants also play a
      major role and can qualitatively modify the type of immune response. The immune
      mechanisms also differ according to the final goal: anti-Plasmodium infection or
      anti-disease vaccine. Over the last few years, the first clinical assays have
      been carried out with the Spf66 vaccine, a synthetic complex protein directed
      against sporozoites and merozoites. In adults and children, the first results in
      South America and in East Africa were modest but encouraging. Unfortunately they
      were not confirmed by further studies in West Africa and South-East Asia. Two new
      types of vaccines are under preliminary clinical evaluation. One is directed
      against ookinetes of Plasmodium falciparum (Pfs25 and Pfs28) and can stop the
      transmission from the mosquito. The other is an anti-sporozoite vaccine with a
      new immunogen (RTS,S) in which the circumsporozoite protein is fused to the
      hepatitis B surface antigen and can protect against infestation. New prospects
      and improvements are offered by the technique of DNA vaccines and will probably
      also result from better knowledge of cellular and molecular biology of the
      parasite which is being extensively studied (genomic structure). If new promising
      perspectives exist, it is particularly important to be careful to avoid such
      disappointments as those caused, in the past, by a too-optimistic and over
      publicized presentation of some preliminary results. It is now certain that one
      or several malaria-vaccines will be available, but no one can seriously say when,
      for whom and how. In any case, it is unrealistic to hope that vaccine(s) alone
      will be able to eradicate such an epidemiologically complex disease as malaria.
      It is probable that only the coordinated use of all the techniques available
      (anti-vectorial protection and fight, chemoprophylaxis and chemotherapy,
      vaccination) will lead to success.

PMID- 9554124
TI  - [Colorectal carcinogenesis, frequency and significance of genetic alterations:
      deletion of the short arm of chromosome 1, and initiating event].
AB  - Cytogenetic anomalies described in colo-rectal tumors are numerous. Despite the
      complexity and the number of the anomalies observed, a combined study of their
      frequency and of the stage of prognosis of the tumors suggests that the evolution
      from colonic adenoma to carcinoma often follows a sequence of events comprising a
      5q15-22 deletion (DCC), and a 17p deletion (P53). It even seems likely that in
      many cases, these events are not constant and that others might lead to the same
      phenotypic transformation. Chromosome 1 involvement in structural rearrangements
      has been demonstrated in numerous forms of cancers, malignant blood disorders and
      in solid tumors. In colorectal adenocarcinoma anomalies have been described on
      short and/or long arms. In a case of adenoma with mild dysplasia a deletion of
      the distal part of the short arm of chromosome 1 was observed as an isolated
      cytogenetic anomaly, suggesting it would be an early, perhaps triggering, event
      for the tumour development. A cytogenetic study in a series of colo-rectal
      tumours, researches on loss of heterozygosity and microsatellite instability lead
      to consider deletions at chromosome 1p as an early event in human colorectal
      tumourigenesis.

PMID- 9554125
TI  - [Examples of foreign countries].
AB  - In France we are not well aware of the health of people in situation of poverty:
      they have not resources enough to care of oneself, not knowing the services of
      social welfare, and not identified by these services. 1) Some studies in Great
      Britain and in U.S. have followed up some deprived groups with health index on a
      long duration: life expectancy at birth, number of stillbirths in the group, low
      birth weight, casualty during childhood, violent deaths among teen agers and
      young men. Disparities between rich and poor are dramatic, unskilled men have a
      mortality three times that of professional men; advantage is given to people who
      had had some education and a steady family home during childhood, compared with
      those who have not. 2) In France investigations have been more accurate on the
      health of deprived individuals: where are they taken care of, who cures them for
      which diseases? According to the results, they are not abandoned. Places for
      reception and care are many, the public institutions welcome them even without
      social security guarantee, almost a hundred non profit associations may help
      them: these discreet institutions are poorly known even by the public
      administration.

PMID- 9554126
TI  - [Access to health care for the destitute].
AB  - An increasing proportion of low income people, in spite of receiving mandatory
      coverage, cannot afford supplementary insurance, and they cannot afford to
      advance payment for care which will lately be reimbursed, nor can they afford
      copayments. The results is that a growing proportion of French population is
      unable to access common care. Faced with this deteriorating situation, parallel
      delivery systems of care have been devised at a local level, facilities have been
      created, and health care providers volunteers to deliver health care to
      underserved populations. To estimate the extent of the phenomenon, CREDES carried
      out a specific survey at the national level. First we identified all health care
      providers or facilities accessible to the underserved. These include traditional
      providers or facilities, such as private physicians and hospitals which agree to
      provide "charity care". There are also new facilities created specifically to
      provide health care to the underserved. The second part of the survey covered the
      human resources, equipment and services offered at these specific facilities. It
      revealed the extensive participation by physicians and nursing staff generally on
      a voluntary basis and the special attention given to the reintegration of the
      underserved into the standard health care system through assistance with the
      necessary administrative procedures.

PMID- 9554127
TI  - [Access to health care for destitute persons at Public Assistance Hospitals in
      Paris].
AB  - All legal French residents are entitled to health care. The 1992 regulatory
      measures, which create a contractual agreement between the government and public
      medical institutions, aim at facilitating access to health care by resolving the
      financial obstacles to accessing health care. The Assistance Publique-Hopitaux de
      Paris (AP-HP) has set up a medical reception center in several hospitals since
      1993. This system is integrated in the general structure of each hospital: in
      some cases, there is a single and centralized unit; in other cases, all
      departments of the hospital, including the emergency room, are involved in caring
      for destitute patients. Whatever the type of the structure may be, social workers
      are a key element to helping the patients recover their social rights. Thirty to
      seventy-percent of patients visiting these centers regain access to social and
      health care coverage. The epidemiological survey of the active file of patients
      revealed that 70% are male, more than 50% are non-French nationals, half of which
      do not have legal immigration status in France. Homeless people represent 40 to
      80% of the population. The average age is around 35. The number of medical visits
      varies greatly from one hospital to another and range from 20 to 60 per month.
      The reasons for visiting the center and the identified medical disorders are
      strongly related to the patients' life conditions and vary significantly with the
      risk factors related to the social and economic situation. The frequency of some
      diseases (psychiatric disorders, tuberculosis, infections by the HIV and HCV) is
      higher in this population than in general population. Delayed visits to the
      medical center represents a severity factor. The hospitals' mission statement is
      not only to ensure that patients facing a precarious social and professional
      situation have equal access to health care, but also to help such patients
      recover their social rights, facilitate their integration in the society and
      fight against social exclusion.

PMID- 9554128
TI  - [Evaluation of the population received and cared for in France in the "Doctors of
      the World" Health Centers].
AB  - For 11 years now, Medecins du Monde's Mission to France has tried to respond to
      the needs of a part of marginalized population, which has no access to health
      care. In 1996, 72,000 consultations have been given throughout the 31 free Health
      centers based in 31 cities in France. Who is this population? Basically young
      people (more than half are under the age of 30 and 10% are underaged), men in 213
      of the cases, living alone, in 80% of the cases. How do they live? Almost 65%
      live with less than 20 francs per day (given by social care); 54% are officially
      jobless. As far as housing is concerned, only 1/4 have a home (women in
      particular). The others live in hostels, self-made shelters, hotels, or with
      relatives; 13% admit living on the street. Why do they come to health centers?
      Almost all diseases observed are identical to the ones detected in regular Health
      care centers, i.e., Ear--Nose and Throat, respiratory and gynecological
      infections. What makes them particular is the fact they are diagnosed later than
      usual, which makes them more serious than usual. The living conditions of this
      marginalized population explain the high frequency of skin problems (12%) and
      neuropsychologic disorders. Why do they come to Medecins du Monde? 1/4 of the
      patients do benefit from social welfare, but are unable to advance the payment of
      medical costs, or support the difference between the actual cost and the
      reimbursement by the Social security. 40% have no social coverage whatsoever.
      However, other motives (1 to 7%) such as administrative problems, rights outside
      their district, refusal to start the administrative procedures, ignorance of
      their rights ... are rarely put forward. The population with no access to health
      care is still unknown. This is why the information gathered is so important. It
      allows a better qualification of the patients' requests and, consequently, a
      better comprehension of the social exclusion phenomenon, particularly in the area
      of health.

PMID- 9554129
TI  - [Recourse to care and morbidity of the homeless in the Paris district].
AB  - The disparities of access to care and morbidity according to different socio
      economic characteristics are highlighted over about thirty years; what is the
      situation with regard to the homeless, the least provided for, who in some sense
      lie at the limits of the social scale? We present data on hospitalizations,
      ambulatory care and the morbidity declared by the homeless revealed in the INED
      survey of February-March 1995 in the Paris region. We tried to compare
      hospitalizations and physician care of the homeless with the population of
      "ordinary households" in the same region on the basis of different statistical
      sources. Hospitalizations are considerably more numerous in this group than in
      the rest of the population which indicates that the homeless are more exposed to
      diseases and accidents; on the other hand, taking into account any possible
      errors of observation, the homeless and the general population seem to have the
      same rate of recourse to outpatient doctor treatment. Is this also the case for
      complementary examinations, biological tests and medical imagery?

PMID- 9554130
TI  - [Toe transplantation in congenital malformations of the hand].
AB  - Toe transfer is a well established procedure for thumb and finger reconstruction
      after mutilation. The indications in congenital malformations are a mater of
      controversy. Out of a personal series of 209 patients, 42 were children
      presenting a congenital malformation. Thirty six, with 46 transfers were
      available for review. There is only one failure at the beginning of our
      experience. The main indication was absence of pinch either due to absence of
      thumb (like in congenital band syndrome or some extreme cases of ulnar club hand
      or cleft hand) or absence of long finger (like in symbrachydactyly monodactylous
      type) or lack of both thumb and finger (like in peromelic type of
      symbrachydactyly). In this last type, we have been disappointed by the functional
      result of the distal implantation of two second toes taken from both feet; we
      have proposed a "stub" operation consisting in a second toe transfer on the
      anterior aspect of the radial epiphysis to take advantage of the mobility of the
      wrist and the availability of plenty tendon transfer (in this proximal
      situation). When planing to "built" an absent pincer, an early age is mandatory
      for operation (mean 12 months), to ensure a good cortical integration. A less
      frequent indication is a partial toe transfer with a vascularized epiphysis to
      provide growth and mobility in some cases of thumb hypoplasia (like in
      symbrachydactyly or Blauth and Manske type III b). Results are difficult to
      assess due to the early operation but if the mobility has been disappointing
      (mean 32 degrees), sensibility (mean 2PD 5 mm) and growth were excellent.

PMID- 9554131
TI  - [Excimer laser: history, development and comparison of equipment].
AB  - We first present the history of the Excimer Laser technological development which
      began in 1975 with Velazco and Sester's research. We report various studies about
      lasers conceiving, treatment parameters, laser-tissues interactions, and
      treatments evolution. In the second part, we compare different Excimer laser
      systems and their capacities. Three current technologies are used for clinical
      application: the broad beam lasers, which use a diaphragm or a disc with multiple
      apertures, the scanning slits and the flying spots. Advantages and disadvantages
      of the various delivery systems are discussed.

PMID- 9554132
TI  - [Laser and corneal surgery: pathological anatomy].
AB  - The studies of the effects of different lasers on the cornea have usually been
      done on animals. These studies show that ultra-violet lasers (Excimer 193 nm, 213
      nm) have a pure photo-ablative effect, without distant lesions. The corneal
      endothelium is always intact as long as the laser beam is acting at a distance of
      more than 50 microns from the cells. The same findings after photo-ablation is
      the presence of a fibroblastic scar after epithelial healing. This scar
      correspond to the haze observed in clinical conditions. The infra-red lasers
      (Intrastomal YAG) produce an important thermal effect the corneal stroma and a
      destruction of the corneal endothelium if influence and frequency are increased.
      In conclusion, the lasers used in corneal surgery appear to be safe for the
      corneal structure but histological studies remain necessary for the new lasers in
      order to be certain of their safety.

PMID- 9554133
TI  - [Laser and corneal surgery: topography and preoperative evaluation].
AB  - The purpose of preoperative clinical examination is to determine accurately the
      refraction under cycloplegia. Operative techniques and protocols are chosen in
      relation to the degree of ametropia. Computer assisted videokeratography allows
      early keratoconus detection and gives reference quantitative datas for analysing
      postoperative changes.

PMID- 9554134
TI  - [Laser and corneal surgery: patient selection].
AB  - The aim of refractive surgery is a good postoperative visual acuity and the
      satisfaction of the patient. To reach this, a good selection of the patient is
      important. Each patient has to be evaluated personally and individually at the
      hand of the next criteria: A complete preoperative examination The motivation and
      the expectations of each patient The possibilities and the complications of each
      operative technique. the contra-indications of the refractive surgery and each
      operative technique. In case of small and moderate myopia, the results of the
      radial keratotomy and the excimer-laser are similar and comparable with each
      other. In case of moderate and high myopia, the excimer-laser (PRK and LASIK) is
      the only valuable operative technique.

PMID- 9554135
TI  - [Treatment of severe myopia using the excimer laser].

PMID- 9554136
TI  - Excimer laser correction of astigmatism using erodible masks.
AB  - PURPOSE: The latest development in the erodible mask technology is an excimer
      laser containing the mask in the laser optical pathway. This paper reports the
      results of the first human series of consecutive treatments performed for the
      correction of compound myopic astigmatism. METHODS: We have treated 83 eyes.
      Spherical equivalent attempted correction ranged between -1.75 and -11.75 D (mean
      -7.07 +/- 2.45 D), astigmatic attempted correction ranged between -1.00 and -5.00
      D (mean -2.42 +/- 1.02 D). The sphere correction was made by diaphragm using a
      multi-zone software with three ablation zones: 100% of the total attempted
      correction for the central 5.0 mm zone, 70% for the second 6.0 mm zone, 30% for
      the outer 6.5 mm zone. Cylinder correction was made sequentially after myopic
      correction using the appropriate mask. RESULTS: One month after treatment, mean
      refractive error was +1.07 +/- 1.24 D (range +4.50/-1.75 D) for spherical
      equivalent, and -0.49 +/- 0.57 D (range +0.75/-2.00 D) for astigmatism. Forty
      eight eyes (57.8%) had uncorrected visual acuity of 20/40 or better. At six
      months, mean refractive error was +0.42 +/- 0.97 D (range +3.75/-1.00 D) for
      spherical equivalent, and -0.44 +/- 0.51 D (range +0.25/-3.00 D) for astigmatism.
      Vector analysis showed that 57 eyes (68.7%) had 5 or less degrees rotation.
      Seventy-two (86.7%) and 54 eyes (65.1%) had uncorrected visual acuity equal or
      better than 20.40 and 20/25 respectively. One eye (1.2%) showed a best corrected
      visual acuity loss of more than one line, but 8 eyes (9.6%) had a gain of more
      than one line. One-year results on a smaller series (33 eyes) overlap the six
      month results. CONCLUSIONS: The mask in-the-rail excimer laser delivery system
      appears to be effective and predictable in the correction of compound myopic
      astigmatism. We observed no significant regression of the astigmatic correction
      over time. Longer follow-up on larger series is necessary to draw final
      conclusions.

PMID- 9554137
TI  - [Treatment of hypermetropia using the Holmium laser--laser thermokeratoplasty
      (LTK)].
AB  - The results of two year follow-up after Holmium LTK are presented. The choice of
      the technique was justified based on experimental, technical and anatomo
      pathological data as well as on the property of the corneal collagen fibers to
      shrink at a temperature of 60-70 degrees C. Although the immediate results were
      encouraging, we found an important regression after two years follow-up,
      resulting in a final correction of maximally 1.5 D, independent on the degree of
      hypermetropia to be treated. These results were obtained with the "contact"
      method, which is in our experience slightly superior to the "non-contact"
      technique. The question is whether the regression will continue with time or will
      stabilize and remain at 1.5 D of hyperopic correction.

PMID- 9554138
TI  - [Surgery in myopic astigmatism: arciform keratotomy and PKR versus PARK].
AB  - Two surgical techniques for treatment of myopic astigmatism are compared: One
      technique is a combined procedure with relaxing incision and photorefractive
      keratectomy (RI PRK), the other one is photoreactive keratectomy done for
      correction of myopia and astigmatism (PARK). Fifty-nine eyes (42 patients) were
      operated by IR PRK. The preoperative myopia was between -1.5 and -14 D and the
      astigmatism between -0.75 and -6 diopters. Thirty-two eyes (20 patients) were
      treated with the PARK. The preoperative myopia was between -1 and -15 D and the
      astigmatism between -0.5 and -4. In 38 cases, relaxing incisions allowed to
      correct astigmatism entirely. The mean preoperative sphere of -6.8 D before PRK
      was 1.4 D and the spheres between -1 and -15 D. Twelve months after treatment, 26
      eyes on 30 were spherical. The spherical equivalent varied between +0.75 and 
      1.50 D. Relaxing arciform incision presents the advantage to correct high
      asymmetric astigmatism without corneal thinning, as well as mixed astigmatism. At
      the present time, the PARK allows to correct only symmetrical myopic astigmatism.
      CONCLUSION: The predictability of the results is high if the cylinder is less
      than 3 D and the sphere less than 6 D. Beyond this limit, there is a higher risk
      of regression, and haze related with the depth of photo-ablation and we prefer RI
      PRK.

PMID- 9554139
TI  - [Excimer laser phototherapeutic keratectomy].

PMID- 9554140
TI  - [Complications in excimer laser photorefractive keratectomy].
AB  - The complications of photorefractive keratectomy with excimer laser for myopia
      depend on preoperative myopia and inter-individual variability in wound healing.
      Loss of best corrected visual acuity is induced by Haze, irregular astigmatism
      and decentration. Haze is more frequent after treatment of high myopia.
      Decentration is a severe complication because its treatment is not well defined
      and is difficult. Corneal ulcerations infectious and non-infectious have been
      reported. Other complications are described: induced astigmatism, over and under
      corrections, central islands, halos, loss of corneal sensitivity, abnormal
      epithelial healing, recurrent epithelial breakdown, sterile corneal infiltrates,
      elevated intraocular pressure, subretinal hemorrhage.

PMID- 9554141
TI  - [Medical treatment in laser (PRK) photoretractive keratotomy].
AB  - The need of medical treatment after photorefractive surgery has been studied by
      reviewing the literature on the subject and comparing their conclusions with our
      clinical experience. Considering the pre-operative and immediate post-operative
      medical treatment, there is a large consensus since the aim is treatment of pain
      and prevention of superinfection. The post-operative considerations for medical
      treatment are more controversial and can be considered as to be useful or
      possibly useful.

PMID- 9554142
TI  - [Deamination of adenine and adenosine in staphylococci].
AB  - Deaminations of adenine and adenosine by pattern strains of 24 staphylococcal
      species, were tested. During 3 hours of incubation of the suspensions of 8
      staphylococci with adenine the liberation of ammonia occurred. The same
      staphylococci accumulated ammonia in the incubation medium with adenosine. The
      Staphylococcus intermedius PCM 2405 strain as opposite to the Staphylococcus
      aureus 536 strain in the media with adenine or adenosine accumulated hypoxanthine
      or inosine, respectively and ammonia. These results indicated that adenine
      deaminase (adenase) and adenosine deaminase activities were associated with the
      cells of the Staphylococcus intermedius PCM 2405 strain. Staphylococci were
      heterogeneous within three species groups with respect to adenine and adenosine
      deaminations. Adenine and adenosine determinations were absent in staphylococci
      belonging to the Staphylococcus simulans species group.

PMID- 9554143
TI  - [The influence of temperature on culture of Staphylococcus aureus for cell
      adhesion to collagen].
AB  - The aim of this study was the investigation of adhesion of 88 S. aureus clinical
      isolates to collagen. The experiments were extended to determine the influence of
      growth temperature on collagen adhesin-collagen interaction. Bacterial adhesion
      to collagen was estimated by using immunoenzymatic assay at absorbance of 492 nm
      and compared with standard curves obtained for 8 different densities of each
      strain. The amount of collagen adhesin was indicated by colour reaction intensity
      measured by immunoenzymatic assay. Hydrophobicity of S. aureus strains was
      measured by aggregation in (NH4)2SO4 test. Almost all S. aureus strains isolated
      from bone and joint infections adhered to collagen whereas only a part of soft
      tissue infections isolates showed this feature. The comparison of adhesive
      properties of S. aureus cells cultured at 21 degrees C, 37 degrees C and 42
      degrees C did not make it possible to indicate the optimal culture temperature
      for S. aureus adhesion to collagen. However, the intensive colour reaction of
      cells cultured at 37 degrees C with anti-collagen adhesin antibodies proves the
      production of the highest amount of this adhesin under the mentioned conditions.
      The influence of growth temperature as well as solid and/or liquid medium on the
      change of S. aureus hydrophobic properties was not observed. The obtained results
      show that the S. aureus growth temperature can be one of the factors influencing
      the staphylococci cells adhesion to collagen.

PMID- 9554144
TI  - [Utilization of Staphylococcus siderophores produced by Corynebacterium and
      Coryneform bacteria].
AB  - The ability of iron utilizing by means of siderophores produced by donor strains
      Coryne-bacterium and coryneform organisms (8 strains) by 24 staphylococcal
      strains was investigated. All the donor strains synthesized catecholate class
      siderophores and two strains also hydroxamate class. The majority of
      staphylococcal strain could utilize these siderophores. Most of strains utilized
      siderophores from Corynebacterium pseudodiphtheriticum and Corynebacterium
      aquaticum as well as chelators from plant pathogens-coryneform organisms. Only
      two staphylococcal strains were not be able to utilize siderophores from all
      donor strains.

PMID- 9554145
TI  - [Susceptibility to antibiotics of Staphylococcus aureus strains].
AB  - Staphylococcus aureus is a very important pathogen in humans about 20% of all
      bacterial infections are caused by S. aureus. Because the staphylococcal
      sensitivity patterns have changed, the aim of this study was to investigate the
      current susceptibility of the S. aureus strains to 9 antibiotics: penicillin (P),
      amoxacillin/clavulanic acid (AMC), erythromycin (E), cortimoxazole (SXT),
      tetracycline (T), chloramphenicol (C), mupirocin (MUP), gentamicin (Ge) and
      vancomycin (Va). Susceptibility testing was performed by disc diffusion
      technique, by the procedure outlined by the National Committe for Clinical
      Laboratory Standards (NCCLS). Susceptibility to methicillin was determined using
      5 micrograms methicillin disks. beta-lactamase production in the penicillin
      resistant strains was detected with nitrocefin impregnated disk (Cefinase, BBL
      Microbiology system). The microbiological characteristics of the samples: 338 of
      the isolates were derived, from noses and the throats 382--from surgical wound
      secretions. The analysis of the results showed that most S. aureus strains
      (82.8%) are penicillin resistant and beta-lactamase producing 13.5% of all
      strains were methicillin-resistant. 16.5%--were erythromycin resistant; 3.2%-
      were cotrimoxazole resistant; 51.4%--were mupirocin resistant; 20.6%--were
      gentamicin resistant. All of the strains were vancomycin sensitive.

PMID- 9554146
TI  - [Sensitivity to disinfectants of methicillin resistant Staphylococcus aureus
      strains (MRSA) and gentamicin resistant strains].
AB  - The aim of the study was to find out whether methicillin-resistant S. aureus
      strains (MRSA) are tolerant in a higher degree to disinfectants, and whether a
      correlation exists between lower sensitivity to these agents and resistance to
      gentamicin. The study was carried out on 30 strains of MRSA and 20 of MSSA
      isolated from various clinical materials in various regions of the country. Among
      the studied MRSA 24 strains were resistant and 6 were sensitive to gentamicin,
      and in MSSA 3 strains were resistant and 17 sensitive to this antibiotic. The
      sensitivity to four disinfectants: Manusan, Sterinol, Septyl R and Lysoformin
      Spezial was determined by measurement of MIC (minimal inhibitory concentration)
      in agar medium. Most MRSA in Poland showed decreased sensitivity to these
      disinfectants. Among gentamicin-sensitive and resistant MRSA strains the
      proportions of strains with higher tolerance of three disinfectants (Manusan,
      Sterinol and Lysoformin Spezial) were very similar. Reduced sensitivity to
      disinfectants was found in all gentamicin-resistant MSSA. These data indicate
      that S. aureus strains possess various mechanisms of tolerance of disinfectants.
      Nearly half the studied strains (46%) had decreased sensitivity to all three
      preparations (Manusan, Sterinol and Lysoformin Spezial) belonging to various
      chemical groups this seems to indicate that increased tolerance to these
      disinfectants is a non-specific feature of S. aureus strains.

PMID- 9554147
TI  - [Production of enterotoxins by Bacteroids fragilis strains--effect of
      clindamycin].
AB  - Four B. fragilis strains were examined: one nonenterotoxigenic (NTBF) and three
      producing enterotoxin (ETBF). The growth of cultures was determined and
      enterotoxin, which is released to the culture medium during growth of strains,
      was detected. BHI broth and BHI broth with addition of subinhibitory doses (sub
      MIC) of clindamycin were applied. Bacterial cultures were incubated at 37 degrees
      C for 48 hours. After 4, 8, 16, 24, 48 hours of cultivation, samples of bacterial
      cultures were collected and the optical density was measured. Then the samples
      were centrifuged, supernatants were filtered through 0.45 micron filters and
      concentrated three times with 5000 D ultrafilters. Prepared samples were kept
      frozen at -70 degrees C until used. The titre of enterotoxin in samples was
      determined on human colon adenocarcinoma cell line HT 29/C1. Neutralization assay
      was performed with culture filtrates, which were enterotoxin-positive and with
      rabbit anti-enterotoxin serum. The results of the experiments indicate that
      enterotoxin is detected after 16 hours of incubation of ETBF strains. Clindamycin
      at subinhibitory concentrations (sub-MIC) inhibits the growth of B. fragilis
      cultures. The antibiotic causes also delay and decrease in enterotoxin production
      by ETBF strains.

PMID- 9554149
TI  - [Establishing the types of Dienes compatibility in clinical Proteus mirabilis
      strains].
AB  - The aim of the study was to use the Dienes phenomenon for the differentiation of
      Proteus mirabilis strains isolated from urine by the method of making possible
      their typing. The subject of the study were 351 strains of Proteus mirabilis
      obtained from the laboratory of the Institute of Pediatrics, Medical Academy in
      Lodz. For establishing of the compatibility type 18 indicator strains were taken,
      each of them had action antagonistic towards all other ones. The results were
      read according to the presence or absence of the demarcation line between
      indicator strains and the studied strain. Out of 351 strains in 190 (54%) the
      reactions were compatible with one or more indicator strains. They were
      classified into 30 Dienes compatibility types. In the view of the simplicity and
      easy performance the method can be used in every microbiological laboratory.

PMID- 9554148
TI  - [Use of the LAL test for quantitative determination of Bacteroids fragilis
      endotoxin].
AB  - The aim of this study was the evaluation of LAL test with chromogenic substrate
      usefulness for the quantitative detection of B. fragilis endotoxin and the
      determination of the amount of endotoxin in culture filtrates of the strains of
      this species. Also, the trial was undertaken to determine the influence of
      clindamycin on endotoxin release from B. fragilis rods to the culture medium.
      Four B. fragilis strains were examined: one nonenterotoxigenic (NTBF) and three
      enterotoxigenic (ETBF). The growth of cultures was determined and endotoxin
      liberated to the culture medium during growth of strains was detected. BHI broth
      and BHI broth with addition of sub inhibitory doses (sub-MIC) of clindamycin were
      applied. Bacterial cultures were incubated for 48 hours at 37 degrees C. Samples
      of bacterial cultures were collected after 4, 8, 16, 24 and 48 hours of
      cultivation, and the optical density was measured. Then the samples were
      centrifuged, supernatants were filtered through 0.45 micron filters and
      concentrated three times with 5000 D ultrafilters. Prepared samples were kept
      frozen at -70 degrees C until used. The amount of endotoxin in samples was
      determined using quantitative LAL test with chromogenic substrate S-2423. The
      results of the experiments indicate that LAL test is the useful method for
      determination of B. fragilis endotoxin concentration. This endotoxin activates
      the enzymatic system present in Limulus polyphemus amebocyte lysate. Endotoxin is
      shed spontaneously by B. fragilis rods to the culture medium during growth.
      Clindamycin at subinhibitory concentrations (sub-MIC) inhibits the growth of
      cultures of examined strains. The antibiotic caused increase in endotoxin amount
      in culture medium.

PMID- 9554150
TI  - [Evaluation of the usefulness of the agglutination test with Mangifera indica
      extract for the identification of pathogenic Yersinia enterocolitica strains].
AB  - The study was performed on 137 Y. enterocolitica strains belonging to various
      serological groups, including 75 03 group strains isolated form human clinical
      material. The agglutination test on slides was carried out on this strains using
      Mangifera indica extract of own production. Agglutinating preparation obtained
      from the seeds of M. indica agglutinated Y. enterocolitica organisms possessing
      the pVY plasmid and CRMOX+ phenotype in dilutions to 1.56 micrograms/ml. In
      identification tests conducted parallelly agglutination solution was used in
      concentrations of 100 and 10 micrograms/ml. All clones of Y. enterocolitica from
      O3 group from cultures at 37 degrees C and with CRMOX+ phenotype possessing the
      pVY plasmid were agglutinated by the extract. Agglutination failed to develop in
      the cultures of these clones incubated at 25 degrees C. Yersinia clones not
      containing the pVY plasmid with CRMOX- phenotype were resistant to agglutination.
      The virulence plasmid was found in 44 out of 75 strains of Y. enterocolitica O3
      and was identified by restriction analysis after plasmid DNA digestion with Eco
      RI enzyme. The obtained results agreed with those of Wauters et al. in 1995 and
      confirmed the opinion of these authors on the usefulness of the test with M.
      indica agglutinin for the identification of virulent Y. enterocolitica strains.

PMID- 9554151
TI  - [Hydrophobic properties of Pseudomonas aeruginosa strains].
AB  - Hydrophobic properties are considered as a factor enhancing the adhesion of
      bacteria to tissue cells. The strains of P. aeruginosa isolated from patients
      with urinary tract infections (UTI), from feces and soil were investigated. It
      shows that over 50% strains isolated from UTI had hydrophobic cell surface. Most
      of all strain investigated (67.9%) is characterized by hydrophobicity what
      probably favours their pathogenicity.

PMID- 9554152
TI  - [Susceptibility of clinical strains of gram-negative rods to selected beta-lactam
      antibiotics].
AB  - The aim of the study was to determine the activity of four beta-lactam
      antibiotics against nosocomial strains of gram-negative bacilli. Two antibiotics
      combined with beta-lactamase inhibitors: timentin (TIC/CLAV) and tazocin
      (PIP/TZB) and two carbapenems: imipenem and meropenem were applied. The clinical
      strains were isolated from patients hospitalized in the following wards: surgery
      and intensive care unit of State Clinical Hospital No 1 in Warsaw. The strains
      were identified in the automatic ATB system using ID 32 E and ID 32 GN strips.
      The susceptibility of isolates to antibacterial agents was determined in the
      automatic ATB system using ATB G- and ATB PSE strips. The susceptibility of the
      strains to imipenem, meropenem, timentin and tazocin was tested by disc-diffusion
      method. 157 strains of gram-negative bacilli were cultured. 100 strains were
      isolated from patients hospitalized in surgical ward and 57 strains from patients
      hospitalized in ICU. Nonfermenting rods dominated among isolated strains-91. The
      results obtained indicate that multiresistant gram-negative rods causing serious
      therapeutic problems are often isolated from clinical specimens. The contribution
      of nonfermenting rods, especially Pseudomonas spp. and Acinetobacter spp. to the
      etiology of infections in hospitalized patients has increased. Infections caused
      by these strains are difficult to cure. Tazocin and carbapenems (imipenem and
      meropenem) are highly active in vitro against the examined strains of gram
      negative bacilli.

PMID- 9554153
TI  - [Breast feeding for prevention of viral acute respiratory diseases in infants].
AB  - The incidence of acute viral respiratory diseases (confirmed by
      immunofluorescence test) was compared in a group of 159 infants aged 0-9 months
      breast-fed at least once daily and in a group of 608 infants of similar age and
      hospitalization duration receiving only artificial food. The incidence was
      significantly lower in breast-fed infants (p = 0.00057), especially in the first
      trimester of life (p = 0.00039). This was valid of all RSV infections (p =
      0.01854) and parainfluenza type 4 virus infections (p = 0.0846). The antibody
      level against parainfluenza type 1 and 3 (HI) and against RSV in IgA class
      (ELISA) was compared with that in mother's milk and serum. No significant
      correlation was found for parainfluenza type 1 antibodies (r = 0.159) and 3 (r =
      0.025), while for RSV the correlation was positive and statistically significant
      though rather low (r = 0.234). No significant correlation was found between milk
      antibody levels and the incidence of acute viral respiratory infections. Breast
      feeding showed a significant influence on the lower incidence of these
      infections, particularly in the first trimester of life. It seems that this was
      associated with a non-specific mechanism rather than with the milk levels of
      specific antibodies.

PMID- 9554154
TI  - [Use of the western blot method for detecting antibodies against proteins of
      various rotavirus strains].
AB  - The aim of this work was to adapt the Western blot method to analyse the humoral
      response to proteins of rotavirus strains having various antigens. 10 serum
      samples from animals immunized with SA11, 18 serum samples from hospitalized
      children with rotavirus infections and 17 serum samples from healthy adults were
      examined for rotavirus antibodies using Western blot. Antibodies against all
      structural rotavirus proteins were detected. The examined sera reacted
      differently with rotavirus proteins depending on the strain used. The highest IgG
      reactivity was observed for Wa and SA11, while the lowest was noted for DS-1. At
      the same time a different level of cross-reactivity of human sera with specific
      proteins of antigenically varying rotaviruses was observed. The sera taken from
      adults showed a lower reactivity with proteins of antigens used compared with
      sera from children. The exception was VP6 of the Ito strain for which the
      reactivity of adult sera was statistically higher. Essential differences in the
      reactivity of children's and adult sera were found mainly in the case of VP2 and
      VP4 belonging to the SA11 strain and VP4 and VP7 of the Ito strain. From these
      investigations we can conclude that the Western blot method may be useful in
      assessing immune response caused by rotaviruses. The results of reactivity of
      some human sera with proteins of strains used indicates that the persons had
      previously been infected by antigenically varied rotaviruses.

PMID- 9554155
TI  - [Use of western blot methods for serodiagnosis of hydatidosis in Poland].
AB  - 46 sera and 1 cerebrospinal fluid samples from 47 patients suspected of
      hydatidosis were examined by Western blot method, and the results were compared
      with those of the indirect haemagglutination, immunoelectrophoresis and an enzyme
      linked immunosorbent assay (ELISA). The examinations confirmed high sensitivity
      and specificity of the reactions with 8 kDa antigenic fraction in the Western
      blot. The above data supported the concept, that serological diagnosis of
      hydatidosis should be carried out using a high sensitivity screening test, such
      as ELISA, then the Western blot method to verify positive results.

PMID- 9554157
TI  - [Clinical genetics in The Netherlands. I. Organization, activities and laboratory
      diagnosis].
AB  - There are seven centres for clinical genetics in the Netherlands. In 1996, some
      63,000 persons (patients and possible carriers of hereditary diseases) were
      tested. In centres for clinical genetics chromosomal studies, biochemical
      diagnostics of hereditary metabolic diseases and DNA diagnostics are integrated
      with genetic counseling and prenatal diagnosis. The borders between the three
      different forms of laboratory testing for congenital anomalies and hereditary
      diseases gradually diminish. The variations of the numbers of laboratory
      examinations, genetic advices and prenatal diagnoses over the last ten years show
      that there is no correlation between these activities and the method of funding.
      Owing to the low prevalence of the diseases involved, the total number of DNA
      diagnoses for monogenic diseases will not increase significantly. However, once
      genetic risk factors of diseases such as cancer, cardiovascular diseases,
      diabetes, asthma, rheumatism, some psychiatric disorders and Alzheimer dementia
      will have been mapped, DNA diagnostics will greatly expand and will have
      implications in a broad area of medicine.

PMID- 9554156
TI  - [Detoxication in opiate addiction and prevention of recurrence: administration of
      naltrexone and cognitive behavior therapy].
AB  - Rapid opiate withdrawal and relapse prevention in opiate addicts are made
      possible by naltrexone, clonidine and diazepam in combination with cognitive
      behavioural therapy according to the Community Reinforcement Approach. In an open
      pilot experiment 12 addicted patients achieved initial detoxification. At follow
      up after a minimum of 6 months, 10 of these had not relapsed. Good results with
      this detoxification method could be booked by selecting highly motivated opiate
      addicts.

PMID- 9554158
TI  - [Clinical genetics in The Netherlands. II. Genetic counseling and prenatal
      diagnosis].
AB  - The main feature of clinical genetics is the involvement of close relatives in
      the diagnostics of a hereditary disorder, and the possible consequences of the
      findings for future generations. Complex genetic counseling is required in cases
      with different, possibly hereditary disorders or congenital anomalies in the
      family or by a syndrome with variable risks of recurrence, depending on the exact
      nature of the disorder; also the difficult, often emotionally charged choices
      with which counselees are faced demands the expertise of a clinical genetic
      centre. Results of follow-up studies after genetic counseling show that
      experience with a handicap or disease in the own environment and the presence of
      healthy issue are the main determinants for the decision about reproduction of
      persons with an enhanced genetic risk who request counseling. Because of the
      great variety in perception of risks and of the severity of a disorder, and
      because of the marked clinical heterogeneity, rigid legislation should be avoided
      in the field of prenatal diagnosis. In the future, the training of the clinical
      geneticist has to be adapted to the rapid progress in human genetics.
      Increasingly, the clinical geneticist will function in collaboration with other
      disciplines such as oncology, obstetrics and gynaecology, paediatrics and
      neurology; in connection with family testing and counseling, there will also be
      more collaboration with primary health care.

PMID- 9554159
TI  - [Current antimicrobial drugs].
AB  - In the past few years several new antibiotics became available, but no major
      inventions as to new treatment strategies were made. There are a few new broad
      spectrum antibiotics for the intravenous route like piperacillin-tazobactam, the
      carbapenem meropenem and the fourth-generation cephalosporins. cefepime and
      cefpirome. New oral antibiotics include the third-generation cephalosporins
      ceftibuten, cefetamet and cefpodoxime and the macrolides clarithromycin and
      azithromycin. The last two have the great advantage of less frequent dosing and
      fewer side effects than erythromycin. Of the two new quinolones, sparfloxacin and
      trovafloxacin, trovafloxacin is the more promising. In the treatment of Gram
      positive infections the glycopeptide teicoplanin became available and the
      combined derivatives quinupristin-dalfopristin may prove valuable in the future.

PMID- 9554160
TI  - [Consensus diagnosis and treatment of arterial intermittent claudication. Central
      Guidance Organization for Peer Review].
AB  - Intermittent claudication is an indicator of increased risk of cardiac and
      cerebrovascular morbidity and mortality and as such a reason to look for
      modifiable risk factors for atherosclerosis. A vascular anamnesis and physical
      examination can reliably exclude presence of peripheral arterial occlusive
      disease in the lower extremities, but cannot reliably demonstrate its presence.
      Certainty about presence or absence of peripheral arterial occlusive disease can
      be obtained by determination of an ankle-brachial blood pressure index. The main
      method for the diagnosis of severity and localisation of stenoses and occlusions
      in the arteries to the legs is the echo-Doppler (duplex) examination. With this
      method the feasibility of percutaneous transluminal angioplasty (PTA) can also be
      determined. Consequently, angiography has lost importance as a diagnostic method
      and is only still indicated as part of an interventional treatment (operation or
      PTA). Treatment should be aimed at both amelioration of symptoms and reduction of
      risk factors for atherosclerosis. A key-stone of the treatment is cessation of
      smoking. The role of pharmacotherapy in reducing symptomatology is only limited.
      Walking exercise can have a positive effect on walking distance and should always
      be tried. PTA is the treatment modality of first choice for stenoses in the
      aortoiliac and femoropopliteal arteries. For segmental occlusions in the iliac
      pathway, also recanalisation by means of PTA (in combination with stent
      placement) is a justifiable treatment option. In all other cases operative
      revascularisations give good functional results. Invasive treatments for patients
      with intermittent claudication should be performed within a multidisciplinary
      team.

PMID- 9554161
TI  - [Decreased quality of cervix mucus under the influence of clomiphene: a meta
      analysis].
AB  - OBJECTIVE: To determine whether clomiphene (citrate) has a negative influence on
      cervical mucus qualities and whether administration of exogenous oestrogens has a
      favourable influence in that case. DESIGN: Meta-analysis. SETTING: Stichting
      Gezondheidszorg Oostelijk Zuid-Limburg, Midwifery School, Kerkrade, the
      Netherlands. METHOD: Relevant articles were searched using the Medline database
      for the years 1980-1996 and the Knowledge Finder search system. The reference
      lists of these articles were studied. All prospective, randomized and controlled
      clinical trials mentioning detailed figures were selected and analysed. RESULTS:
      Six articles met all criteria for analysis of the effect of clomiphene on
      cervical mucus. Clomiphene 50 mg/day had an unfavourable influence on cervical
      mucus (not significant), but clomiphene 100 and clomiphene 150 mg/day did have a
      significant effect, the relative risk of unfavourable cervical mucus being more
      than seven in comparison with women not using clomiphene (respective odds ratios
      7.90 (95% confidence interval: 4.15-15.00) and 7.50 (1.97-28.60)). Four articles
      met all criteria for analysis of the effect of exogenous oestrogens on cervical
      mucus of women being treated with clomiphene. Exogenous oestrogens resulted in
      improvement of the cervical mucus qualities in these women (odds ratio: 2.87
      (1.76-4.69)). CONCLUSION: The influence of clomiphene 50 mg/day on cervical mucus
      is not significantly unfavourable, unlike the influence of clomiphene 100 and 150
      mg/day. Exogenous oestrogen administration improves this cervical mucus. In all
      patients being treated with clomiphene the cervical mucus qualities should be
      investigated.

PMID- 9554163
TI  - [Lichen sclerosus et atrophicus as a cause of genital lesions in a girl].
AB  - In a 10-year old girl with irritated vulva lichen sclerosus et atrophicus (LSA)
      was diagnosed. She was successfully treated with local application of equal
      amounts of a cortisol ointment and zinc oil. LSA is a disease of the skin
      infrequently seen in children, and then mostly in girls. Diagnosis is based on
      typical lesions in the anogenital region (sharply delineated ivory discoloration,
      moderate sclerosis and atrophy, haemorrhagic erosions). Knowledge of this disease
      is important in order to distinguish it from sexual abuse.

PMID- 9554164
TI  - [Joint decision making, how? Physician-patient communication about palliative
      treatment].

PMID- 9554165
TI  - Extended-spectrum beta-lactamases: an actual problem of hospital microbiology (a
      review).
AB  - Although there is a variety of mechanisms of bacterial resistance to beta-lactam
      antibiotics, the most important one is production of beta-lactamases inactivating
      penicillins and cephalosporins. The classification of beta-lactamases is based on
      biochemical, enzymological (i.e. molecular structure, inhibitory property,
      substrate-profile, relative rate of hydrolysis) and immunological characters.
      Extended-spectrum beta-lactamases (ESBLs) can be derived from TEM or SHV enzymes.
      These enzymes have now been sequenced and it has been found that relatively few
      point mutations have occurred in the gene of the TEM and SHV type enzymes. These
      point mutations clustered in five areas of the gene. The amino acid mutations can
      alter the conformation, the active site and change the hydrance of beta-lactamase
      cephalosporin binding capacity. So the enzyme is able to bind and hydrolyse the
      third generation cephalosporins. Successive mutation interacted radically
      increasing the binding capacity of enzymes and confer resistance to newer
      cephalosporins. The use of these drugs provides a strong selective pressure to
      develop these mutations. Sporadic nosocomial outbreaks due to strains producing
      an ESBL led to an epidemic problem in some hospitals resulting in a concurrent
      dissemination of genes, plasmids or strains. Clinical epidemiological importance
      and role of ESBLs and emergence of multiply resistance of bacteria of nosocomial
      importance are discussed in this brief.

PMID- 9554166
TI  - Clinical, laboratory, and serological findings of adult Hungarian hospitalized
      acute hepatitis patients, and possible source of the infection.
AB  - Clinical, epidemiological features of acute viral hepatitis of 331 hospitalized
      adult patients were evaluated. HA, HB, HC, and non A-C H were diagnosed in 36.6%,
      34.1%, 10.6%, and 18.7%, respectively. Age of HA cases was significantly lower
      than that of other cases. Only HA showed seasonal variation. Acquisition of HA
      was often associated with visits in endemic areas when compared with all other
      types, while HB, HC, and non A-C H were rather associated with iatrogenic events
      (blood transfusion, surgical procedures, and hospitalization). Symptoms of fever
      and diarrhea, and high ESR were more frequent in HA than in other types, while
      signs of weight loss and high levels of ALT, AST, and S.T.B, and decreased PT
      index were significantly more frequent in HB. Cholestasis course was found in
      1.7%, 0.9%, and 3.2% of patients with HA, HB, and non A-C H, respectively.
      Fulminant course was found only in 0.9% of HB patients. Factors as sex and age
      had no effect on severity of acute phase in HA, HC, and non A-C H, while only the
      age of patients was inversely associated with severity of acute phase in H B.

PMID- 9554167
TI  - Compact growth of Staphylococcus haemolyticus in soft agar is not due to
      hydrophobic interaction between the cocci.
AB  - It was hypothesized that the formation of compact colony in soft-agar both in the
      presence and absence of serum, characteristic mainly for strains of the species
      Staphylococcus haemolyticus among coagulase-negative staphylococci [Szucs et al.
      Acta Microbiologica Hungarica 40:181-189 (1993)] was due to hydrophobic
      interaction between cocci. The effect of a number of surface active agents on
      this phenomenon was examined. Neither 0.1% and 1%. Tween-80 nor 5% and 10%
      ethylene glycol and polyethylene glycol nor 0.1%-4% trypsin influenced the colony
      morphology in soft-agar prepared in modified Staphylococcus 110 broth. Bovine
      lactoferrin and apolactoferrin at concentrations of 0.1%-0.4% made compact
      colonies transient to diffuse ones. Thus, cocci are not adhered to each other in
      compact ball-like colonies by hydrophobic interaction or trypsin-sensitive
      proteins. It is possible that still unknown polysaccharide-binding proteins or
      other trypsin-resistant proteins are responsible for the formation of compact
      colonies by Staphylococcus haemolyticus in soft-agar.

PMID- 9554169
TI  - A new selective method for isolation of Haemophilus species.
AB  - Chocolate agar with teicoplanin disk (30 micrograms) was used for the isolation
      of Haemophilus strains. Fifty strains of 3 Haemophilus species grew as well in
      the inhibition zones of teicoplanin disks as on teicoplanin containing selective
      plates, whereas Gram-positive bacteria failed to form colonies. This selective
      method proved especially advantageous when Haemophilus strains were isolated from
      mixed bacterial cultures of 665 specimens.

PMID- 9554168
TI  - Growth of microorganisms on rubbers and plastics. Medical aspects of
      microbiological corrosion and the role of quality control.
AB  - The cause of nosocomial infections and their possible solutions, according to the
      chemical compounds of rubber and plastic equipments are shortly summarized.
      Compounds of rubbers and plastics act as culture medium for bacteria and fungi
      being causative agents in nosocomial infections and because of their long-term
      persistence they can be source of such infections. This problem needs cooperation
      between experts and specialists from different scientific fields working in both
      industry and medicine. Only "united forces" can make steps in order to find
      solutions to these emerging questions and problems.

PMID- 9554170
TI  - Bacterial endotoxins and nonspecific resistance.
AB  - The stress situations, including medical intervention (e.g. operations, antitumor
      drugs, irradiation, etc.) decrease the nonspecific resistance of the body. In
      these situations patients people have greater chance to get an opportunistic
      infection than healthy ones. The restoration or elevation of the activity of
      immune system in injured patients is a very important task of medicine. Minute
      amounts of bacterial endotoxin (LPS)--given parenterally--can elevate the
      nonspecific resistance. Unfortunately this beneficial influence is associated
      with noxious properties. Irradiation (60 Co-gamma; 150 kGy) is a good technique
      for the detoxification of LPS. The radiodetoxified endotoxin (RD-LPS) preparation
      (so-called TOLERIN) is less toxic but its beneficial properties is preserved. On
      the basis of animal experiments and clinical trials TOLERIN could be a suitable
      preparation for regeneration of the lymphoreticular-immune system and elevation
      of nonspecific resistance.

PMID- 9554171
TI  - The role and importance of Endre Hogyes in the history of Hungarian microbiology.

PMID- 9554172
TI  - Clinical significance of alimentary tract microbes in bone marrow transplant
      recipients.
AB  - A prospective study on the microbes isolated from the alimentary tract in 120
      bone marrow transplant (BMT) recipients (1991-1993) was undertaken to define the
      spectrum of organisms isolated under antimicrobial prophylaxis, their temporal
      sequence of emergence, and the associated morbidity and mortality. Clostridium
      difficile (n = 20), isolated in the pre-engraftment and early post-engraftment
      periods (day 2-45 post-BMT), was the most common microbe recovered from stool of
      patients with diarrhea. In contrast to previous reports, no significant
      difference in mortality was observed between patients with and without C.
      difficile isolated in stool. Two patients had neutropenic ileocecitis with
      concomitant bacteremia due to Escherichia coli and Klebsiella pneumoniae. One
      patient was found to have astrovirus gastroenteritis (day 7), and Giardia lamblia
      was recovered from the stool of another (day -7). Heavy growth of Staphylococcus
      aureus from direct smear-positive specimens was found from the upper airway of
      two patients with severe mucositis and complete dysphagia (day 12 and 23).
      Salmonella spp. of groups B and E were found in the stool of five asymptomatic
      patients at the time of conditioning. No specific organisms was recovered from
      the endoscopic brushing of two patients with lower end esophagitis, three
      patients with upper gastrointestinal bleeding, and three patients with perirectal
      cellulitis. During the post-engraftment period, five patients had documented
      cytomegalovirus gastroenterocolitis (days 34-97), one had Mycobacterium chelonae
      colitis (day 70), and another had nodular gastritis due to Acremonium falciforme
      (day 270). Overall, only 28% of patients with alimentary tract symptoms/syndrome
      had specific pathogens isolated from clinical specimens. Differentiation of the
      causation of alimentary tract symptoms was often difficult because noninfectious
      complications such as conditioning toxicity, graft-versus-host disease, and its
      treatment often caused alimentary tract symptoms in addition to predisposed BMT
      patient to infection. The reluctance of obtaining tissue biopsy for ascertaining
      the importance of those potential alimentary tract pathogens often dictate the
      use of empirical treatment.

PMID- 9554173
TI  - The role of copper on ethambutol's antimicrobial action and implications for
      ethambutol-induced optic neuropathy.
AB  - The principal side effect of the antimycobacterial agent ethambutol (EMB) is an
      optic neuropathy with clinical features very similar to a mitochondrial
      hereditary optic neuropathy (Leber's). The mechanism of EMB-induced optic
      neuropathy may be EMB's chelation of copper, thereby precluding normal cytochrome
      c oxidase activity and mitochondrial metabolism in the optic nerve. Before
      attempting to use therapeutic copper to replenish endogenous stores in an attempt
      to preclude EMB-induced optic neuropathy, we wished to determine whether EMB is
      still effective against mycobacteria in the presence of copper. EMB and copper,
      alone and in combination, were tested against six strains of Mycobacterium
      tuberculosis and five strains of Mycobacterium avium using a radiometric broth
      macrodilution assay. Copper did not effect EMB's antimicrobial actions against
      either species of mycobacteria. This in vitro study suggests that if copper were
      given to patients to prevent EMB-induced optic neuropathy, it would not
      compromise EMB's bacteriostatic properties.

PMID- 9554174
TI  - In vitro activity of LY333328 against vancomycin-resistant enterococci,
      methicillin-resistant Staphylococcus aureus, and penicillin-resistant
      Streptococcus pneumoniae.
AB  - We report the activity of LY333328 against 35 clinical isolates of vancomycin
      resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and
      vanC-2/3 genes, as determined by PCR), 33 clinical isolates of methicillin
      resistant S. aureus, and 29 clinical isolates of high-level penicillin-resistant
      S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by
      2 micrograms/mL LY333328, and 8 micrograms/mL LY333328 was bactericidal against
      all isolates tested. All isolates of methicillin-resistant S. aureus were
      inhibited by 1 microgram/mL LY333328, and 4 micrograms/mL LY333328 was
      bactericidal against all methicillin-resistant S. aureus isolates tested. All
      isolates of penicillin-resistant S. pneumoniae were inhibited by < 0.125
      microgram/mL LY333328, and 0.25 microgram/mL LY333328 was bactericidal against
      all S. pneumoniae isolates tested. LY333328 is a promising new glycopeptide
      antimicrobial agent.

PMID- 9554175
TI  - In vitro assessment of the antimicrobial activity of a local sustained release
      device containing amine fluoride for the treatment of oral infectious diseases.
AB  - Dental caries and periodontal diseases are chronic infectious diseases caused by
      oral bacteria. Local sustained release delivery systems extend the time in which
      the drug is present in the oral cavity, thus enhancing its therapeutic potential
      while reducing its side effects. Amine-fluorides (AmF) are known anticaries
      agents and have recently been found to have an antibacterial effect against
      periodontal pathogens and caries-associated bacteria. The purpose of this in
      vitro study was to assess the antimicrobial activity of a local sustained release
      device (LSRD) containing AmF on Streptococcus sobrinus 6715. LSRD was prepared
      from an ethylcellulose matrix containing AmF. Release kinetics of AmF from the
      LSRD was measured simultaneously with its antimicrobial activity. The organic
      amine and the fluoride were released in different kinetics profiles: The fluoride
      was released faster than the organic amine. The antimicrobial activity of AmF was
      measured on planktonic bacteria in solution and on bacteria as part of
      experimental dental plaque. During a 10-day period, the concentration of the
      released AmF was above its MIC and no bacterial growth was observed. Bacterial
      counts in the dental plaque were reduced by 1 to 2 log units. Hence, the LSRD
      containing AmF has the potential to serve as a medicament in prevention and
      treatment of dental caries and periodontal diseases.

PMID- 9554176
TI  - In vitro activity of oral antimicrobial agents against clinical isolates of
      Pasteurella multocida.
AB  - Pasteurella multocida causes a wide variety of infections and is the most common
      localized soft tissue infection after animal bite injuries. Penicillin or
      amoxicillin has been considered agent of choice for therapy. Reported beta
      lactamase production by some isolates, the therapeutic dilemma of the penicillin
      allergic patient, and the polymicrobial nature of some infections led to this
      study of alternate antimicrobial agents. The in vitro activity of ampicillin,
      amoxicillin/clavulanate, cefprozil, cefuroxime, erythromycin, clarithromycin,
      trimethoprim/sulfamethoxazole, ciprofloxacin, and tetracycline were compared to
      penicillin against 73 geographically diverse isolates of P. multocida from human
      infections collected since 1991. MIC90 (microgram/mL) were as follows: penicillin
      < or = 0.06; ampicillin < or = 0.5; amoxicillin/clavulanate < or = 0.5; cefaclor
      1.0; cefprozil 1.0; cefpodoxime 0.06; cephalothin 2.5; cefuroxime < or = 0.25;
      erythromycin 2.0; azithromycin 1.0; clarithromycin 4.0;
      trimethoprim/sulfamethoxazole < or = 0.5/9.5; ciprofloxacin < or 0.25;
      tetracycline < or = 2.0. No beta-lactamase producing isolates were found in this
      study. This in vitro study has identified alternate oral agents to penicillins
      that may be appropriate for therapy of P. multocida infections.

PMID- 9554177
TI  - Emergence of ciprofloxacin resistance in Escherichia coli isolates after
      widespread use of fluoroquinolones.
AB  - The evolution (from 1990 to 1996) of fluoroquinolone consumption and resistance
      and the current patterns of fluoroquinolone usage were examined in a 250-bed
      community hospital in Spain. Fluoroquinolone consumption increased from 1392 g in
      1990 to 3203 g in 1996 (p < 0.05). A significant increase in ciprofloxacin
      resistance was observed in Escherichia coli isolated from urine samples (from 3
      to 20%, p < 0.00001), but not in those E. coli isolated from blood or other
      sample cultures. In 69 randomly selected clinical charts, fluoroquinolone was
      used as prophylaxis, empirical therapy, and specific directed therapy in 20%,
      65%, and 15%, respectively. Evaluation of quinolone indication was: first choice
      agents (29%), alternative agents (49%), experimental agents (4.3%) and, agents
      with no role (1.4%). Our study shows that the increase in the use of
      fluoroquinolones is associated with the emergence of ciprofloxacin-resistant E.
      coli from urinary tract sources. Based on their indications, current quinolone
      usage can be greatly reduced.

PMID- 9554178
TI  - Comparative in vitro and bactericidal activity of oxazolidinone antibiotics
      against multidrug-resistant enterococci.
AB  - Increasing resistance among enterococci poses a considerable therapeutic problem.
      In this study, we evaluated the comparative in vitro activity of two
      investigational oxazolidinone antibiotics, eperezolid and linezolid, versus
      clinical isolates of multidrug-resistant enterococci. One hundred isolates (16
      Enterococcus faecalis, 69 E. faecium, 10 E. gallinarum, 2 E. casseliflavus, 1 E.
      avium, 1 E. hirae, and 1 E. raffinosus) evaluated were collected from diverse
      geographic areas in North America and Europe from 1991 to 1995. Eperezolid MIC50
      and MIC90 were 1.0 microgram/mL and 2.0 micrograms/mL (1.0-2.0 micrograms/mL
      range). Linezolid MIC50 and MIC90 were 2.0 micrograms/mL and 2.0 micrograms/mL
      (0.5-2.0 micrograms/mL range), respectively. MICs were the same at 10(3) CFU/mL
      and 10(8) CFU/mL initial inoculum. In time-kill experiments using 10 strains and
      concentrations of 4 micrograms/mL, 8 micrograms/mL, and 16 micrograms/mL
      (achievable serum concentrations) of eperezolid and linezolid there was a 2 log10
      reduction of growth for 2 of 10 isolates tested using eperezolid and a 1 log10
      reduction for 50% of isolates with both agents. There was indifferent
      bactericidal killing when either oxazolidinone was combined with gentamicin,
      ampicillin, or streptomycin for isolates lacking these resistances. This study
      demonstrates these oxazolidinone agents to have excellent in vitro activity
      versus multidrug-resistant enterococci.

PMID- 9554180
TI  - National surveillance of nosocomial blood stream infection due to species of
      Candida other than Candida albicans: frequency of occurrence and antifungal
      susceptibility in the SCOPE Program. SCOPE Participant Group. Surveillance and
      Control of Pathogens of Epidemiologic.
AB  - A national surveillance program of nosocomial blood stream infections (BSI) in
      the USA between April 1995 and June 1996 revealed that Candida was the fourth
      leading cause of nosocomial BSI, accounting for 8% of all infections. Forty-eight
      percent of 379 episodes of candidemia were due to species other than Candida
      albicans. The rank order of non-C. albicans species was C. glabrata (20%) > C.
      tropicalis (11%) > C. parapsilosis (8%) > C. krusei (5%) > other Candida spp.
      (4%). The species distribution varied according to geographic region, with non-C.
      albicans species predominating in the Northeast (54%) and Southeast (53%)
      regions, and C. albicans predominating in the Northwest (60%) and Southwest (70%)
      regions. In vitro susceptibility studies demonstrated that 95% of non-C. albicans
      isolates were susceptible to 5-fluorocytosine, and 84% and 75% were susceptible
      to fluconazole and itraconazole, respectively. Geographic variation in
      susceptibility to itraconazole, but not other agents, was observed. Isolates from
      the Northwest and Southeast regions were more frequently resistant to
      itraconazole (29-30%) than those from the Northeast and Southwest regions (17
      18%). Molecular epidemiologic studies revealed possible nosocomial transmission
      (five medical centers). Continued surveillance for the presence of non-C.
      albicans species among hospitalized patients is recommended.

PMID- 9554179
TI  - Multicenter evaluation of the in vitro activity of six broad-spectrum beta-lactam
      antimicrobial agents in Puerto Rico. The Puerto Rico Antimicrobial Resistance
      Study Group.
AB  - The minimum inhibitory concentrations of 6 broad-spectrum beta-lactam
      antimicrobial agents were determined by use of the Etest versus a total of 569
      bacteria in 7 Puerto Rican hospital laboratories. These included 342 recent
      clinical isolates of Enterobacteriaceae, 63 Pseudomonas aeruginosa, 54
      Acinetobacter species, and 110 oxacillin-susceptible staphylococci. Extended
      spectrum beta-lactamase production was noted among 11% of Klebsiella pneumoniae
      isolates. Hyperproduction of Amp C cephalosporinase was observed with > 20% of
      isolates of Enterobacter spp., Serratia spp., and Citrobacter freundii. The
      overall rank order of activity of the six beta-lactams examined in this study
      versus all clinical isolates was imipenem (95.8% susceptible) > cefepime (91.1%)
      > piperacillin/ tazobactam (82.3%) > cefotaxime (77.6%) > piperacillin (72.5%) >
      ceftazidime (67.0%).

PMID- 9554181
TI  - Identification of oxacillin-susceptible and oxacillin-resistant Staphylococcus
      aureus using commercial latex agglutination tests.
AB  - Four hundred thirteen Staphylococcus sp. were identified by Staphaurex,
      Staphaurex Plus, and BACTiStaph kits using tube coagulase as reference. Among 222
      coagulase-positive isolates, 56 were oxacillin-resistant Staphylococcus aureus.
      All tests were accurate in distinguishing between coagulase-positive and 
      negative staphylococci with sensitivities and specificities > or = 97% and only
      nine discrepancies.

PMID- 9554182
TI  - Timed kill kinetic studies of levofloxacin, ofloxacin, and ciprofloxacin against
      Moraxella catarrhalis.
AB  - Levofloxacin bactericidal activity was compared to ciprofloxacin and ofloxacin
      against 10 strains of Moraxella catarrhalis. The cidal action (by kill-curve
      analysis) was slightly more rapid for levofloxacin, but all tested
      fluoroquinolones were considered bactericidal for all strains tested, including
      those producing BRO-1 and 2 beta-lactamases.

PMID- 9554183
TI  - Individual differences in P300 amplitude: a genetic study in adolescent twins.
AB  - Using quantitative genetic research designs, we decomposed phenotypic variance in
      P300 parameters into genetic and environmental components. The twin method was
      used to carry out this decomposition. Event related potentials (ERPs) were
      measured during a visual oddball paradigm in a sample of 213 adolescent twin
      pairs. The presence of male and female same-sex and opposite-sex twins in the
      sample enabled us to study sex differences in the contributions of genetic and
      environmental effects to P300 parameters. For targets and nontargets, half of the
      variance in the P300 amplitude is attributable to factors shared by the family
      members. However, it remains unclear whether this resemblance is attributable to
      shared environmental or genetic influences. The same factors (genetic or shared
      environmental) were found to contribute to the individual differences in males
      and females. The contributions do, however, differ across gender. Multivariate
      genetic analyses investigated the covariance among various brain areas to
      determine whether the covariance between two or more leads is attributable to the
      same genetic and/or the same environmental factors. The covariance of the P300
      amplitude measured at different locations was attributable both to unshared
      environmental and to shared factors. Again it was not possible to show that the
      shared factors where either genetic or shared environmental.

PMID- 9554184
TI  - Context effects in a category verification task as assessed by event-related
      brain potential (ERP) measures.
AB  - This study examined the extent to which decisions about category membership
      (between category structure) are dependent on or dissociable from the typically
      structure (within category structure) of categories. To this end, behavioral and
      event-related brain potential (ERP) measurements were obtained in a category
      verification task that incorporated a context manipulation (list composition
      effect) that was previously shown to affect membership verification. In a German
      and an American English version of the experiment, pairs of words were presented
      and subjects were asked to decide whether or not the second word was an exemplar
      of the superordinate indicated by the first word. Both versions yielded similar
      results. The behavioral data showed that both typicality and context manipulation
      affected the verification times for the true exemplars. Furthermore, atypical
      true exemplars were affected more by context manipulation than mere typical ones.
      By contrast, the N400 component of the ERPs elicited by the true exemplars was
      influenced by typicality, but invariant in the face of the context manipulation.
      These results underscore the previously shown dissociation between reaction times
      and N400 changes and suggest that category membership decision (as reflected in
      verification times) and semantic relatedness or typicality of an exemplar (as
      reflected in N400 modulation) can vary independently from each other and,
      therefore, likely index the activity of different brain systems.

PMID- 9554185
TI  - ERP components elicited in response to warning stimuli: the influence of task
      difficulty.
AB  - A series of experiments were conducted to systematically evaluate the relative
      contributions of task difficulty and stimulus probability to P300 amplitudes.
      Scalp event-related potentials (ERPs) were recorded and the topographic
      distributions were evaluated during a multi-level cognitive task with an
      antecedent warning. In three separate studies, task difficulty (five levels),
      probability or expectedness (10-60%), and randomness (random or blocked
      presentation) were manipulated. Response accuracy, subjective ratings, and
      reference-free averages of the P300 components elicited by the warning stimuli
      were evaluated. Statistical analysis indicated that significantly larger P300s
      were associated with the more difficult task warnings except when memory tasks
      were presented in a blocked design, suggesting that neither task difficulty nor
      probability alone can account for variations in the P300 in a multi-level task
      scenario. Results are discussed with regard to adaptation-level theory.

PMID- 9554187
TI  - EEG changes index camouflaged object identification: a pilot study.
AB  - EEG correlates of camouflaged object identification were investigated in this
      pilot study by recording 8-s epochs of scalp potentials under two conditions. In
      the experimental condition subjects, three female and two male right-handers,
      aged 23-47, viewed images depicting camouflaged target objects, and signalled
      identification by blinking. In the control condition subjects viewed a neutral
      screen and blinked at will. Theta band activity was analysed for linear
      associations using cross-correlation. Correlation increased over a 1-s interval
      preceding. Associations included, progressively, occipital and left temporal
      regions, bilateral frontal and temporal areas, and bilateral occipital, temporal,
      central, frontal and prefrontal regions. A descriptive model is presented,
      according to which a unitary percept is the emergent result of a process of self
      organisation of a network of interregional signalling.

PMID- 9554186
TI  - Event-related potentials can reveal differences between two decision-making
      groups.
AB  - Previous research has shown that a complex decision is dependent on an underlying
      utility metric that is used by decision making processes to accumulate preference
      for one alternative. This study postulated that a state of indecision may arise
      if this underlying metric is poorly organized. The underlying metric was examined
      with a paired comparison task while measuring event-related potentials (ERP) for
      subjects classified as 'career decided' and 'career undecided'. Stimuli for
      comparison were presented either sequentially or simultaneously. The simultaneous
      condition produced results consistent with the hypothesis that undecided subjects
      have a poorly organized value metric as revealed in both the behavioral data and
      the P3 component. A relationship between P3 amplitude and word distance on the
      underlying metric was found only for the decided group. This was interpreted in
      terms of the previously documented relationship between P3 and the constructs of
      decision confidence and task difficulty.

PMID- 9554188
TI  - BUN/creatinine ratios: aid to decision making about delayed imaging in Tc-99m red
      blood cell scans for gastrointestinal hemorrhage.
AB  - In patients with gastrointestinal hemorrhage, delayed or late scans with Tc-99m
      labeled red blood cells are readily performed and have prognostic impact when
      early images are negative. Nevertheless, there have been no indicators for the
      likelihood of detecting bleeding on such images. In a review of all
      gastrointestinal bleeding scans over an 8-year period, 73 patients had delayed
      images (> 3 hours) following early negative exams. For these patients,
      determinations of serum blood urea nitrogen (BUN) and creatinine (Cr) were
      evaluated as the BUN/Cr ratio and were compared against delayed scan findings and
      confirmed diagnoses. Patients with significant renal failure were excluded from
      analysis. There were 34 late positive (46%) and 39 late negative (54%) studies.
      Mean BUN/Cr was 26.5 and 20.0 in patients with late positive and late negative
      scans, respectively (p < 0.05). Occurrence of late positive scans was 38% (19/50)
      for BUN/Cr < 25.0 vs. 65% (15/23) for BUN/Cr > 25.0 (p < 0.05). Patients with
      early negative images and a BUN/Cr ratio of 25 or greater have a greater
      likelihood of a positive delayed image. Late imaging should be encouraged in
      patients with elevated BUN/Cr and early negative scintigraphy.

PMID- 9554189
TI  - Coexistent parathyroid adenomas and Hurthle cell tumors: failure of full
      detection by subtraction method.
AB  - Tc-99m sestamibi and I-123 sodium iodide studies were performed on two patients,
      one with a neck mass and another with suspected hyperparathyroidism. Subtraction
      images, detected what proved to be Hurthle cell tumors in each case, but
      coexisting parathyroid adenomas, which were found at surgery, were not
      visualized. The findings indicate that both types of lesions can occur
      simultaneously, and that studies are needed to determine whether detailed assays
      of rate of washout could distinguish between the lesions.

PMID- 9554190
TI  - The diagnostic utility of dual phase Tc-99m sestamibi parathyroid imaging.
AB  - PURPOSE: Primary hyperparathyroidism is a disease of uncertain etiology that
      results from hypersecretion of parathyroid hormone (PTH) by the parathyroid
      gland. In most institutions, the preferred imaging protocol utilizes a dual-phase
      technique with Tc-99m sestamibi which is reported to be more sensitive than
      earlier protocols involving TI-201 with Tc-99m pertechnetate subtraction. The
      purpose of this study is to evaluate the accuracy and clinical utility of Tc-99m
      sestamibi dual-phase scintigraphy for localizing hyperfunctioning parathyroid
      tissue. MATERIALS AND METHODS: We retrospectively reviewed thirty-nine
      consecutive hyperparathyroid patients who received a dual-phase Tc-99m sestamibi
      parathyroid scan. Thirty-seven of the subjects subsequently underwent a bilateral
      neck exploration and parathyroidectomy. Each scan interpretation was then
      correlated with the histopathologic diagnosis and the patients' post-surgical
      clinical course. RESULTS: The sestamibi dual-phase imaging protocol correctly
      localized 21 of 25 parathyroid adenomas and identified 8 out of 10 cases of
      hyperplasia. Our overall sensitivity and specificity were 83% and 75%,
      respectively. In addition, four of the adenomas were successfully localized
      intraoperatively using a gamma probe. CONCLUSION: Parathyroid imaging with
      sestamibi appears to be superior to TI-201/Tc-99m pertechnetate subtraction based
      on the reported results of both techniques at various institutions. Dual-phase
      sestamibi imaging appears to be useful and cost-effective for presurgical
      localization of hyperfunctioning parathyroid tissue. In addition, sestamibi
      imaging in conjunction with an intraoperative probe is a very promising technique
      that has the potential to provide both localization information of a suspected
      parathyroid adenoma and to facilitate its surgical removal by reducing operation
      time.

PMID- 9554191
TI  - Postinfectious cerebellitis: clinical significance of Tc-99m HMPAO brain SPECT
      compared with MRI.
AB  - PURPOSE: We compared Tc-99m HMPAO brain SPECT and MRI with the clinical findings
      in a case of a 14-year-old boy with post-infectious cerebellitis. RESULTS: Tc-99m
      HMPAO brain SPECT scan showed marked reduction in perfusion to the left anterior
      lobe, left lateral hemisphere, and left posterior lobe of the cerebellum. The MRI
      showed a limited region of abnormal signal in the mid posterior left cerebellar
      hemisphere. Since the patient's overall neurological deficit was characterized by
      ataxia, nystagmus, head and body titubation, dysmetria, dysdiadochokinesia, loss
      of normal check, and rebound testing attributed to the involvement of the
      anterior, lateral, and posterior lobes of the left cerebellar hemisphere, the Tc
      99m HMPAO brain SPECT finding correlated better with the extent of functional
      neurological deficits. CONCLUSION: Tc-99m HMPAO brain SPECT may better assess
      cerebellar signs and symptoms in cerebellitis since the blood flow abnormalities
      correlated with dysfunction of the cerebellum, whereas the MRI abnormalities did
      not encompass the scope of the neurological deficits.

PMID- 9554192
TI  - Significance of early tubular extraction in the first minute of Tc-99m MAG3 renal
      transplant scintigraphy.
AB  - Renal transplant perfusion curves obtained using Tc-99m MAG3 differ from those
      with Tc-99m DTPA. The perfusion curve can be divided into a first phase (up to
      the first-pass peak) and a second phase (the curve after the initial peak). The
      second phase of the MAG3 perfusion curve is usually ascending in contrast to the
      descending Tc-99m DTPA curve. This ascending MAG3 curve reflects early tubular
      extraction of MAG3. However, the second phase of the MAG3 curve is sometimes flat
      or descending. We hypothesized that a flat or descending curve reflects poor
      early tubular extraction and therefore graft dysfunction. Ninety-two studies of
      59' renal transplant patients were retrospectively reviewed. The second phase of
      the perfusion curve was visually classified as ascending, flat, or descending.
      77.2% of studies had ascending curves, 16.3% flat curves, and 6.5% descending
      curves. A descending curve had a positive predictive value (PPV) of 100% for
      medical graft dysfunction, while a flat curve had a PPV of 93.3%. A nonascending
      second phase curve was specific (96.4%) but not sensitive (33.9%) for graft
      dysfunction. Patients with acute tubular necrosis were not significantly more
      likely to have a nonascending curve than those with acute rejection. There was no
      significant difference in creatinine level between patients with medical graft
      dysfunction and ascending vs. nonascending curves. A nonascending second phase Tc
      99m MAG3 perfusion curve is predictive for graft dysfunction. An ascending curve
      is nonspecific and can be seen in both normally and poorly functioning grafts.

PMID- 9554193
TI  - Demonstration of double-chambered right ventricle on myocardial perfusion SPECT.
AB  - A 19-year-old man with a double-chambered right ventricle (DCRV) and an
      associated ventricular septal defect was admitted to the hospital for surgical
      correction. Preoperative study of myocardial perfusion with Tc-99m tetrofosmin
      SPECT depicted the two chambers of the right ventricle. There was a substantial
      differential in the radioactive uptake between these two chambers. The inflow and
      outflow chambers with different peak-pressures (94 and 18 mm Hg) showed different
      uptakes reflecting the pressure difference, which was intense in the inflow
      chamber and weak in the outflow.

PMID- 9554195
TI  - Thyroid hemiagenesis accompanying a thyroglossal duct cyst: a case report.
AB  - A case of thyroid hemiagenesis discovered incidentally in a patient presenting
      with a thyroglossal duct cyst is reported. Thyroid embryology is briefly
      reviewed. Various characteristics of thyroid hemiagenesis and thyroglossal duct
      cysts are explored.

PMID- 9554194
TI  - Acute cholecystitis in AIDS patients: correlation of Tc-99m hepatobiliary
      scintigraphy with histopathologic laboratory findings and CD4 counts.
AB  - BACKGROUND: AIDS patients are susceptible to opportunistic gastrointestinal
      infections including ascending cholangitis and cholecystitis, especially if CD4
      count is < 200. Incidence of acalculous cholecystitis has not been reported
      previously. PURPOSE: We aim to evaluate the incidence of acalculous cholecystitis
      in AIDS patients and to identify causative organisms and mortality rate following
      cholecystectomy. MATERIALS AND METHODS: We reviewed the files of 46 patients in
      order to meet the objectives of this study. RESULTS: CD4 counts were < 200 in 31
      patients and > 200 in 15 patients. HIDA imaging was performed in 31 patients; in
      8, the CD4 count was > 200 and all had calculous cholecystitis. The gallbladder
      was visualized in 3 patients for a sensitivity of 63% and no organisms were found
      in the gallbladder specimens. In 23 patients, the CD4 count was < 200; the
      gallbladder was visualized in 5 patients for a HIDA sensitivity of 78%; 16 (52%)
      had acalculous cholecystitis; and 15 had calculous cholecystitis. In acalculous
      cholecystitis, Cryptosporidium was found in six cases, cytomegalovirus (CMV) in
      six cases, and fungus, yeast, tuberculosis, and mycobacterium avium intracellular
      each in one case. The thirty day mortality rate was 18%; 5 of 28 who underwent
      open cholecystectomy died within 30 days, 4 of them with a CD4 count < 200. There
      was no mortality in the 26 patients who underwent laparoscopic cholecystectomy.
      CONCLUSION AND RECOMMENDATIONS: (1) Because of the high incidence of 52% of
      acalculous cholecystitis in AIDS patients with a CD4 count < 200, we recommend
      using intravenous cholecystokinin if the gallbladder is visualized on
      hepatobiliary scintigraphy in order to determine gallbladder ejection fraction
      and exclude acalculous cholecystitis. (2) Laparoscopic rather than open
      cholecystectomy should be the surgical procedure of choice in AIDS patients
      especially if the CD4 count is < 200.

PMID- 9554196
TI  - Tc-99m pertechnetate scintigraphy for the detection of ileal duplication.

PMID- 9554197
TI  - Gardner's syndrome with bone scintigraphic and CT demonstration.

PMID- 9554198
TI  - Lateral displacement of liver and bowel on renal imaging.

PMID- 9554199
TI  - SPECT in the early diagnosis of Creutzfeldt-Jakob disease.

PMID- 9554200
TI  - Retrocardiac uptake of Tc-99m sestamibi: manifestation of a hiatal hernia.

PMID- 9554201
TI  - Hyperthyroidism: an underappreciated cause of diffuse bone disease.

PMID- 9554202
TI  - Warthin's tumor demonstrated with Tc-99m pertechnetate SPECT and CT.

PMID- 9554203
TI  - Ga-67 and Tc-99m HMPAO labeled WBC imaging in erythema nodosum leprosum reaction
      of leprosy.

PMID- 9554204
TI  - Tc-99m sestamibi planar and SPECT imaging of a retrotracheal parathyroid adenoma.

PMID- 9554205
TI  - Extraskeletal accumulation of bone-seeking agent mimicking diaphragmatic uptake.

PMID- 9554206
TI  - Tc-99m MDP scintigraphy of temporal bone metastasis from breast carcinoma.

PMID- 9554207
TI  - Tc-99m DMSA and Tc-99m MAG3 findings in crossed renal ectopia.

PMID- 9554208
TI  - Three phase bone imaging in a patient with fulminant meningococcemia.

PMID- 9554209
TI  - False-positive I-131 deposition in a parotid gland duct ectasia.

PMID- 9554210
TI  - Tc-99m sestamibi esophageal activity during myocardial imaging.

PMID- 9554211
TI  - Bone scan in ossifying fibromyxoid tumor of soft parts.

PMID- 9554212
TI  - Injection artifact on FDG PET imaging.

PMID- 9554213
TI  - Current readings in nuclear medicine.

PMID- 9554214
TI  - Recognition and consequences of obstructive sleep apnea hypopnea syndrome.
AB  - There is a growing recognition of sleep-disordered breathing (SDB) in patient
      groups and in the general population. This article reviews issues related to
      recognizing the disorder, including the problems of relying on narrowly defined
      polysomnographic data for case findings and for assessment of disease severity.
      The distributions of symptoms and physiologic measurements of SDB in the
      population and their inter-relationships are reviewed. The epidemiological data
      that address risk factors and consequences of sleep apnea hypopnea syndrome
      (SAHS) also are discussed, with recommendations regarding recognition priorities.

PMID- 9554215
TI  - Pathophysiology of upper airway obstruction during sleep.
AB  - Obstructive sleep apnea is a common medical disorder with significant adverse
      health consequences. The pathogenesis of pharyngeal obstruction during sleep,
      however, remains elusive. This article addresses the key mechanisms of upper
      airway (UA) obstruction including the role of transmural pressure, pharyngeal
      compliance, pharyngeal dilating muscle activity and non-neuromuscular factors. A
      proposed scheme of the pathophysiology of UA obstruction is outlined.

PMID- 9554216
TI  - Upper airway imaging.
AB  - Upper airway imaging is a powerful technique to study the mechanisms underlying
      the pathogenesis, biomechanics, and efficacy of treatment options in patients
      with obstructive sleep apnea. Imaging studies have provided significant insight
      into the static and dynamic structure, and function of the upper airway and
      surrounding soft-tissue structure during wakefulness and sleep. Upper airway
      imaging modalities primarily include nasopharyngoscopy, cephalometrics, computed
      tomography (CT), and magnetic resonance (MR) scanning. These imaging modalities
      have been used to study the effect of respiration, weight loss, dental
      appliances, and upper airway surgery on the upper airway. MR imaging and CT have
      allowed quantification of the airway and surrounding soft-tissue structures in
      three dimensions. Clinical indications for upper airway imaging are evolving for
      patients being treated with dental appliances and upper airway surgery.

PMID- 9554217
TI  - Positive pressure therapy.
AB  - Positive airway pressure in the treatment of obstructive sleep-disordered
      breathing (OSDB) is reviewed. Continuous positive airway pressure (CPAP), bilevel
      positive airway pressure, and variable (auto-CPAP) pressure, their mechanisms of
      action, benefits, and complications are examined. A perspective on the future of
      positive airway pressure therapy for OSDB is provided.

PMID- 9554218
TI  - Oral appliances in the treatment of snoring and sleep apnea.
AB  - Oral appliances have been developed that are effective in snoring patients and in
      patients with mild to moderate sleep apnea. This article reviews the types of
      appliances that are available, their possible modes of action, and their
      efficacy. In addition, the clinician is provided with guidelines on how to choose
      the appropriate patient for this therapy.

PMID- 9554219
TI  - Surgical management of obstructive sleep apnea syndrome.
AB  - This article discusses the history of operative management of obstructive sleep
      apnea syndrome and reviews a protocol for surgical intervention. An overview of
      diagnostic procedures and evaluation is also presented, and emerging technology
      for the management of this disorder is touched on.

PMID- 9554220
TI  - Decision making in obstructive sleep-disordered breathing. Putting it all
      together.
AB  - Obstructive sleep-disordered breathing consists of a spectrum ranging from the
      upper airway resistance syndrome to complete apnea. Although this disorder is
      relatively common, it is still under-recognized, resulting in a significant
      increase in morbidity and mortality. In this article, we describe the rationale
      for treating this disorder. Then, using the best available evidence, we try to
      develop a systemic approach to the problem, covering recognition, diagnosis, and
      treatment.

PMID- 9554221
TI  - Sleep apnea in congestive heart failure.
AB  - Sleep-related breathing disorders, including obstructive sleep apnea (OSA) and
      Cheyne-Stokes respiration with central sleep apnea (CSR-CSA), commonly occur in
      patients with congestive heart failure (CHF). In this setting they can have
      adverse pathophysiologic effects on the cardiovascular system. OSA may lead to
      development or progression of left ventricular (LV) dysfunction by increasing LV
      afterload through the combined effects of elevations in systemic blood pressure
      and a generation of exaggerated negative intrathoracic pressure, and by
      activating the sympathetic nervous system through the influence of hypoxia and
      arousals from sleep. Abolition of OSA by continuous positive airway pressure
      (CPAP) can improve cardiac function in patients with CHF. In contrast to OSA, CSR
      CSA is likely a consequence rather than a cause of CHF. Here, pulmonary
      congestion causes hyperventilation by stimulating pulmonary irritant receptors.
      This leads to reductions in PaCO2 below the apneic threshold during sleep,
      precipitating posthyperventilatory central apneas. CSR-CSA is associated with
      increased mortality in CHF, probably because of sympathetic nervous system
      activation caused by recurrent apnea-induced hypoxia and arousals from sleep.
      Treatment of CSR-CSA by supplemental O2, theophylline, and CPAP can alleviate
      central apneas. Of these treatments, however, only CPAP has been shown to improve
      cardiac function and symptoms of heart failure. We conclude that effective
      treatments of OSA and CSR-CSA may prove to be useful adjuncts to the standard
      pharmacologic therapy of patients with CHF.

PMID- 9554222
TI  - Sleep in patients with chronic obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) become hypoxemic
      during sleep, particularly during rapid eye movement (REM) sleep. Those who are
      most hypoxemic when awake experience the most severe hypoxemia during sleep. The
      major cause of REM hypoxemia is hypoventilation, with additional contributions
      from alteration in ventilation/perfusion matching and functional residual
      capacity (FRC) reduction. REM hypoxemia probably contributes to the development
      of pulmonary hypertension and polycythemia and may predispose to cardiac
      arrhythmias in some patients. The most effective form of therapy is nocturnal
      oxygen therapy, but the indications for the use of nocturnal oxygen therapy are
      entirely based on daytime oxygenation levels. Routine polysomnography is not
      indicated in patients with COPD but should be performed in patients who have
      symptoms suggestive of coexisting sleep apnea/ hypopnea syndrome.

PMID- 9554223
TI  - Sleep in asthma.
AB  - The nocturnal worsening of asthma is a major cause of morbidity and mortality
      from this disease. The physiologic changes that occur during normal sleep can
      have adverse effects on breathing patterns, arousal responses, and airway
      clearance in asthmatics. Understanding of these alterations in airway mechanics
      and airway inflammation may lead to better management of this disease.

PMID- 9554224
TI  - Hypoventilation syndromes.
AB  - In summary, alveolar hypoventilation can be associated with a diverse group of
      disorders, collectively referred to as the hypoventilation syndromes. Most have
      associated hypercapnia and hypoxemia while awake, with a significant worsening in
      gas exchange during sleep. In some disorders, gas exchange abnormalities are
      manifested only during periods of sleep. Signs and symptoms suggestive of the
      underlying disorder leads one to investigate for associated hypoventilation.
      Proper diagnosis allows the implementation of appropriate therapy, which may both
      improve gas exchange and associated symptoms, and impact overall survival.

PMID- 9554225
TI  - Insomnia.
AB  - This article reviews issues involved in the diagnosis of insomnia and discusses
      treatment options, including pharmacologic treatment, which is indicated mainly
      in acute insomnia. Sleep hygiene is then discussed. Finally, the various
      behavioral treatments are reviewed, including light therapy, relaxation training,
      cognitive therapy, sleep curtailment, and stimulus control therapy.

PMID- 9554226
TI  - Narcolepsy and idiopathic hypersomnolence.
AB  - Narcolepsy is among the leading causes of excessive daytime sleepiness. Its
      classic form associates daytime sleepiness with cataplexy, sleep paralysis,
      hypnopompic hallucinations, and nocturnal disrupted sleep. This form is
      associated with HLA DQ betal-0602 in about 85% to 90% of affected subjects,
      independently of their ethnicity. But the definition of the variants of
      narcolepsy remains controversial, despite the fact that, in some cases,
      narcolepsy may be limited to daytime sleepiness. In its classic form, it is
      associated with two or more sleep onset rapid eye movement periods at the
      Multiple Sleep Latency Test. This test, performed after nocturnal
      polysomnography, can be helpful in diagnosing narcolepsy, in the absence of a
      convincing history of partial or complete attacks of cataplexy--a pathognomonic
      symptom. Investigation of narcoleptic Dobermans has indicated that a muscarinic
      cholinergic hypersensitivity exists in the brain of affected animals and
      abnormalities involve also the dopaminergic system. Despite its prevalence of
      0.03% to 0.05%, it is still a neurologic entity often missed. Investigations of
      families of narcoleptics, including monozygotic twins, indicate that this
      syndrome is polygenic in nature with association of environmental factors. As the
      peak of onset of disabling symptoms occurs between 15 and 25 years of age, it is
      important to improve the treatment of this lifelong, disabling illness.
      Stimulants medications, independently of their mode of action, are prescribed to
      help daytime sleepiness, and tricyclic antidepressant drugs or serotonergic
      reuptake blockers are used on the other symptoms. But these medications have a
      limited efficacy. Short naps at regular intervals during the day are a strong
      therapeutic adjuvent.

PMID- 9554227
TI  - Parasomnias including the restless legs syndrome.
AB  - The three states of mammalian being, W, REM sleep, and NREM sleep, are not
      mutually exclusive, and may occur simultaneously, oscillate rapidly, or appear in
      dissociated or incomplete form to produce primary sleep parasomnias. In addition,
      dysfunctions of a wide variety of organ systems may take adwide variety of organ
      systems may take advantage of the sleeping state to declare themselves, resulting
      in secondary sleep parasomnias. Contrary to popular opinion, the majority of the
      often bizarre and frightening experiences are not the manifestation of underlying
      psychological or psychiatric conditions. There is an interesting interaction
      between sleep-disordered breathing and parasominas. Formal study in an
      experienced sleep disorders center will usually reveal a diagnosable and
      treatable condition that explains the spells. Continued study of unusual sleep
      related events undoubtedly will reveal more fascinating conditions, expanding our
      knowledge of sleep physiology, and strengthening the bonds between clinicians and
      basic-science sleep researchers.

PMID- 9554228
TI  - Monitoring sleep and breathing: methodology. Part I: Monitoring breathing.
AB  - There is considerable variation in monitoring techniques and definitions of sleep
      disordered breathing. Work underway in the Sleep Heart Health Study may help to
      clarify these issues. Home and portable monitoring have the potential to improve
      cost and convenience of diagnosis and treatment of sleep disorders but are
      currently indicated only in specific instances. Detection and monitoring of
      pediatric sleep-disoriented breathing varies considerably from that of adults.

PMID- 9554229
TI  - Current and future methodology for monitoring sleep.
AB  - Sleep is much more than simply decreased consciousness, and the distinctions
      among the stages of nonREM and REM sleep are of significance for the
      polysomnographer because of their implications for physiologic events. The rules
      for staging sleep are essentially unchanged since their original description in
      1968. This article describes this system for sleep staging, some of its
      weaknesses, and potential new approaches.

PMID- 9554230
TI  - A look toward the future.
AB  - There will be many changes in the sleep field in the next 5 to 10 years. These
      will include increments in our knowledge of the basic neurobiologic mechanisms
      driving sleep and the impact of sleep loss on general health. The technology used
      in the sleep laboratory will likely change as well, leading to a larger range of
      available tests and new ways to conduct standard ones. Finally, as the knowledge
      base in sleep increases, the expertise required to practice sleep medicine will
      rise, leading to a better-trained, more focused practitioner.

PMID- 9554231
TI  - The porphyrias. Commentary.

PMID- 9554232
TI  - The porphyrias. Historical perspective.

PMID- 9554233
TI  - Evolution of porphyrins.

PMID- 9554234
TI  - The biochemistry of heme synthesis in porphyria and in the porphyrinurias.

PMID- 9554235
TI  - Genetic defects in the porphyrias: types and significance.

PMID- 9554236
TI  - How genetic defects are identified.

PMID- 9554237
TI  - Enzyme assays and the porphyrias: which tissues and when indicated.

PMID- 9554238
TI  - Clinical features of the porphyrias.

PMID- 9554239
TI  - Porphyria cutanea tarda of the toxic and sporadic varieties.

PMID- 9554240
TI  - Clinical laboratory methods for diagnosis of the porphyrias.

PMID- 9554241
TI  - Treatment of the cutaneous porphyrias.

PMID- 9554242
TI  - Management of acute attacks in the porphyrias.

PMID- 9554243
TI  - Lessons from the porphyrias of animals.

PMID- 9554244
TI  - Norplant consensus statement and background review.
AB  - This review has highlighted the attributes of a very important new method of
      contraception. The signatories to this document agree that, with the provision of
      appropriate information and instruction for the user, Norplant is a good
      contraceptive choice to be made available worldwide in family planning programs
      that have the resources for appropriate training and counseling. The signatories
      to this document are acting in their own personal capacity and not as
      representatives of any particular organization.

PMID- 9554245
TI  - Oral contraceptive use and benign gynecologic conditions. A review.
AB  - The following review considers the main epidemiologic data on oral contraceptives
      (OC) and the risk of major benign gynecologic diseases. Earlier studies
      investigating the relationship between OC use and functional ovarian cysts
      indicated that the use of high-dose combination OC have a protective effect,
      whereas low-dose monophasic or multiphasic pills have little or no effect. With
      regard to seromucinous cysts, the scanty data available are consistent with the
      notion of some protection of OC in current but not in former users, although
      possible effects of diagnostic and selection bias should be considered. Published
      data on the relationship between fibroids and OC appear too scattered to allow a
      precise quantification of risk. In any case, any relationship is moderate and,
      hence, of limited clinical and public health relevance. The data on OC and benign
      gynecologic conditions are reassuring in their absence of any consistent excess
      risk.

PMID- 9554246
TI  - Continuation rates of long-acting methods of contraception. A comparative study
      of Norplant implants and intrauterine devices.
AB  - Following adverse widespread publicity in the United Kingdom and the United
      States, it is commonly believed that discontinuation rates for the contraceptive
      implants Norplant in the UK are high. We have compared discontinuation rates
      between new intrauterine device (IUD) users (253 women) and new Norplant implant
      users (502 women) over 33 months following the introduction of Norplant implants
      among a population of women attending the same clinic and counseled in the same
      manner by the same group of providers. Women choosing the IUD were slightly older
      and were more likely to be changing their contraceptive method because of
      dissatisfaction with their current method. Nor plant implant users were more
      likely to have completed their families. Continuation rates for Norplant implants
      were significantly higher than for IUD at 12, 18, and 24 months after insertion.
      At 24 months, continuation rates for Norplant implants were 72% compared with
      rates of 55% for IUD users. Higher continuation rates may be related more to
      factors associated with the providers than with the users of these two long
      acting methods.

PMID- 9554248
TI  - Thromboembolic stroke in young women. A European case-control study on oral
      contraceptives. Transnational Research Group on Oral Contraceptives and the
      Health of Young Women.
AB  - A matched case-control study was performed between 1993 and 1996 in 16 centers in
      the United Kingdom, Germany, France, Switzerland, and Austria. The objective was
      to determine the influence of oral contraceptives (OC), particularly those
      containing modern progestins, on the risk for ischemic stroke in women aged 16-44
      years. A total of 220 women who had had an incident ischemic stroke and were
      compared with 775 control subjects who were unaffected by stroke. At least one
      hospital and one community control subject per patient was matched and
      interviewed with the corresponding patient for 5-year age band and for area of
      residence. Crude odds ratios (95% confidence intervals [CI]) for ischemic stroke
      were as follows. For current use of any OC versus no use 2.3 (1.7-3.2), the
      adjusted odds ratio (OR) 3.6 (2.4-5.4). The OC associated risk was higher for
      first generation than for second or third generation OC. The risk estimates for
      patients versus community control subjects were always lower than for hospital
      control subjects. No major regional difference of the risk estimates was found.
      Compared with nonusers of OC without hypertension, women with hypertension who
      used OC had an almost 10-fold increased risk. However, OC users who had had a
      blood pressure check before OC prescription had a lower risk than did those
      without such a check. Smoking > 10 cigarettes/day is associated with higher risk
      of stroke, particularly for OC users. No significant effect was found for
      duration of OC use. We conclude that although there is a small relative risk of
      occlusive stroke for healthy women currently using OC, the attributable risk is
      very small because the incidence in this age group is very low. The small
      increase in risk of OC use may be further reduced by preventive efforts for
      cardiovascular risk factors, particularly hypertension and smoking.

PMID- 9554247
TI  - Effectiveness of Cyclofem in the treatment of depot medroxyprogesterone acetate
      induced amenorrhea.
AB  - A total of 100 women who were using depot medroxyprogesterone acetate (DMPA) for
      contraception and who had experienced at least 6 months of drug induced
      amenorrhea, were randomized to either switching their method of contraception to
      Cyclofem, or continuing with DMPA. At the end of 6 months, 82% of the Cyclofem
      users had experienced some vaginal bleeding, compared with 10% of DMPA users.
      Time to resumption of vaginal bleeding was related to the duration of DMPA use to
      the duration of DMPA induced amenorrhea, and to the body mass index of the user.
      Over the 6 months of follow-up, 94% of Cyclofem users complained of some side
      effects, compared with 22% of DMPA users. The most frequently cited problems
      among Cyclofem users included breast tenderness, abdominal pain, and
      dysmenorrhea; yet a third of these women opted to stay on Cyclofem at the end of
      the study. It is concluded that switching to Cyclofem is a new option for DMPA
      users who are concerned about amenorrhea. Although using Cyclofem in this setting
      will not meet the needs of all such women, its effectiveness in inducing vaginal
      bleeding justifies a trial in those who have no contraindication to estrogen
      treatment.

PMID- 9554249
TI  - A regimen of oral contraceptives restricted to the periovulatory period may
      permit folliculogenesis but inhibit ovulation.
AB  - Increased safety of oral contraceptives (OC) has resulted from a reduction in the
      estrogen and progestin content per tablet. A reduction in the number of
      hormonally active pills and their placement at critical points within the cycle
      may provide a novel regimen for further reducing the hormonal content of OC per
      cycle and their attendant side effects without compromising efficacy. The
      objective of this study was to determine the effectiveness of two OC regimens
      that incorporate a delayed start and limited midcycle use of the combination of
      ethinyl estradiol and norethindrone, and limited use of norethindrone only during
      the second half of the cycle. Main outcome measures were defined as ovulation,
      serum concentrations of estradiol (E2), luteinizing hormone (LH), follicle
      stimulating hormone (FSH), progesterone (P), follicular diameters, and
      endometrial thickness. Volunteers were issued blister packs containing 28 pills
      and randomized to one of two groups. Group 1 used a combination of 50 micrograms
      ethinyl estradiol and 1 mg norethindrone per tablet day 6-10, and 0.70 mg
      norethindrone only day 11-19. Placebo tablets were used on days 1-5 and day 20
      28. Group 2 used a combination of 50 micrograms ethinyl estradiol and 1 mg
      norethindrone per tablet on day 8-12, and 0.70 mg norethindrone only on day 13
      21. Placebo tablets were used on day 1-7 and day 22-28. A total of 20 cycles were
      studied using 10 volunteers. To assess any possible carryover effect, two
      successive cycles were studied for each subject. Serum sampling for E2, FSH, LH,
      and P, and transvaginal ultrasound imaging to assess endometrial thickness and
      follicle diameter were carried out at 4 day intervals throughout the cycle. One
      ovulation occurred in 10 cycles in group 1. Five ovulations occurred in 10 cycles
      in group 2. All ovulations, regardless of group, occurred in the second cycle.
      Peak E2 concentrations were not significantly different between groups (152.04 +/
      107.1 pg/mL vs 162.1 +/- 56.1 pg/mL [mean +/- SD] for groups 1 and 2,
      respectively] but occurred earlier in the cycle in group 1. No differences were
      noted between the groups in serum concentrations of FSH or LH for any given cycle
      day. Maximum follicle diameters were not different between groups 1 and 2,
      regardless of ovulatory status (20.5 +/- 8.1 mm2 vs 20.6 +/- 14.2 mm2,
      respectively). Ultrasound imaging assessment of midcycle follicle growth revealed
      diameters ranging from 18.5 mm2 to 34.0 mm2 with gradual resolution through the
      second half of the cycle in anovulatory cycles, and 16.0 mm2 to 23.5 mm2 with
      abrupt disappearance in ovulatory cycles. Endometrial thickness did not exceed 10
      mm for any anovulatory cycle regardless of group, but ranged from 6 to 9 and 6 to
      11 during the luteal phase of ovulatory cycles of groups 1 and 2, respectively.
      Peak serum P concentrations at midluteal phase in ovulatory cycles ranged from
      9.2 ng/ml to 18.2 ng/ml. Data from this preliminary study suggest that ovulation
      may be prevented with a combination of ethinyl estradiol and norethindrone
      started as late as cycle day 6 and limited to 5 days' duration using
      norethindrone only for 9 days during the second half of the cycle. Such a
      restricted regimen may offer both an effective method of contraception and a
      means of further reducing both estrogen and progestin content per cycle and the
      possible short and long term adverse side effects of these hormones.

PMID- 9554250
TI  - Dimeric inhibin serum values as markers of ovarian activity in pill-free
      intervals.
AB  - Levels of inhibin A and B as well as other hormones in serum samples obtained
      during the pill-free interval in women taking combined oral contraceptives (OC)
      were measured to asses the extent of ovarian activity during that period. Type of
      pill and day of pill-free interval were recorded during routine gynecologic check
      ups, if patients were in the pill-free period and had taken their pills regularly
      in the previous cycle. In addition to inhibin A and B, serum levels of follicle
      stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and
      progesterone were also quantified. Inhibin B levels rise significantly in
      parallel with rising levels of FSH, LH, and E2. Progesterone levels were
      completely suppressed and inhibin A levels rose slightly but insignificantly.
      Inhibins are sensitive biochemical markers of ovarian activity in pill-free
      intervals.

PMID- 9554251
TI  - Corrosion behavior of copper in a copper bearing intrauterine device in the
      presence of indomethacin.
AB  - As an improvement to the use of the copper bearing intrauterine device,
      indomethacin has been introduced to reduce the incidence of bleeding after
      insertion of the device. The effects of indomethacin on copper corrosion were
      studied in vitro in simulated uterine fluid. Electrochemical polarization
      resistance measurements indicated that indomethacin powder slightly increased the
      corrosion rate of copper if pH of the fluid was not under control and it did not
      change the corrosion rate if pH was adjusted daily to maintain some constancy.
      The experimental results for medication by indomethacin-releasing Silastic were
      basically the same as those with powdered indomethacin. X-ray diffraction showed
      that only cuprous oxide was formed on the copper substrated surface and that
      indomethacin did not affect the corrosion products. As scanning electron
      microscopy demonstrated, however, in the presence of indomethacin the oxide
      particles formed were found to be more coarse and dense than in the absence of
      indomethacin.

PMID- 9554253
TI  - Oral contraceptives and risk of venous thromboembolism: impact of duration of
      use.

PMID- 9554252
TI  - Effect of inhibitors of enzymes involved in polyamine biosynthesis pathway on
      pregnancy in mouse and hamster.
AB  - The syntheses of polyamines, which play a definitive role in cell proliferation
      and tissue growth during early embryogenesis, are believed to be principally
      regulated by two enzymes: ornithine decarboxylase (ODC) and polyamine oxidase
      (PAO). However, when the level of enzyme ODC goes down, another enzyme known as S
      adenosyl methyl decarboxylase (SAMDC) is believed to up-regulate the biosynthetic
      pathway. In the present study, the effects of inhibitors of enzymes SAMDC and PAO
      were determined in mated hamster and mouse in peri-and immediate postimplantation
      stages of pregnancy. It was noticed that, whereas the SAMDC inhibitor (MDL-73815)
      failed to arrest the pregnancy in the hamster in spite of raising the dose to 100
      mg/kg, the PAO inhibitor (MDL-72527DA) was found to be 100% effective at 75 mg/kg
      in both species. The results confirmed the role of enzyme PAO in promoting early
      development of the embryo.

PMID- 9554254
TI  - The mode of action of immunological adjuvants.
AB  - Adjuvants augment immune responses to antigens and influence the balance between
      cell-mediated and humoral responses, as well as the isotypes of antibodies
      formed. New adjuvant formulations include antigen-carrying vehicles and small
      molecules with immunomodulating activity. Widely used two-phase vehicles comprise
      liposomes and microfluidized squalene or squalane emulsions. These are believed
      to target antigens to antigen-presenting cells, including dendritic cells (DC),
      follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement
      generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby
      stimulating the proliferation of the latter and the generation of B-memory.
      Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating
      agents induce the production of cytokine cascades. In a primary cascade at
      injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes
      migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the
      maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a
      secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which
      induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell
      mediated immune responses and the formation of antibodies of protective isotypes,
      such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes
      activate complement and collaborate with antibody-dependent effector cells in
      protective immune responses.

PMID- 9554255
TI  - Will adjuvants be needed for vaccines of the future?
AB  - Adjuvants improve the uptake of antigens by the immune system, and stimulate
      antigen-presenting cells (APC) to express "danger signals" such as the secretion
      of cytokines. The physical changes in antigen distribution can also be brought
      about by DNA vaccines, which provide persistent antigenic stimulation, access to
      the endogenous antigen processing pathway and, with the appropriate mode of
      injection, targeting to APC; however the question of whether DNA vaccines induce
      danger signals is unresolved. This presentation reviews the particular features
      of the adjuvant action of Al(OH)3, muramyl dipeptides and saponins, and the
      danger signals they induce in APC to ascertain whether they provide clues as to
      how DNA vaccines might be improved. Three conclusions are drawn: (i) adjuvants
      differ in the relative efficacy with which they stimulate Th1 and Th2 cells; (ii)
      IL-1 is the only identified common danger signal induced by the three adjuvants;
      (iii) in the case of both muramyl dipeptides and saponins there are toxic and
      nontoxic analogues, and the adjuvant activity can be separated from the toxicity.
      The basis of the difference between the toxic and non-toxic analogues is not
      clear.

PMID- 9554256
TI  - Adjuvants and delivery systems for viral vaccines--mechanisms and potential.
AB  - Of the vaccines against viral diseases of man currently available, several are
      less than satisfactory, and the present surge of interest in improving such
      vaccines, and in developing new vaccines against viral diseases as yet
      unchallenged, has led to major developments in three areas. The capacity to
      identify the nature and form of antigenic epitopes in proteins allows the
      specific design of molecular entities to promote relevant and protective immune
      responses. Such entities, although ideal in terms of specificity and purity, may
      not achieve their goals through failure to reach relevant cells of the immune
      system due to simple dilution, elimination by host enzymes or lack of specific
      targeting. Concomitant with the above there has been development of a plethora of
      adjuvants aimed at enhancing immune responses to these 'new' immunogens,
      paralleled by an almost equally rapid increase in understanding the complex
      nature of the immune response, particularly with respect to antigen processing,
      the nature and role of cytokines and the importance of T-cell subsets in
      infection. These developments allow exploration of matching the properties and
      mechanistic action of a given adjuvant to a defined immune response. Adjuvants
      can be grouped according to their physical characteristics and mode of action.
      They include particulate adjuvants, oil and emulsifier-based adjuvants, those
      providing controlled antigen delivery, adjuvants based on specific targeting of
      antigen, and gel-type adjuvants. They may act non-specifically in promoting an
      immune response to an antigen through depot formation, or very specifically as in
      a "delivery system" where an antigen is linked to a cellular protein, targeted to
      a specific cell receptor. As adjuvant technology develops it is becoming
      increasingly clear that these differing approaches may be combined, and an
      adjuvant/delivery system designed, to provide slow release of a targeted antigen.
      The role of adjuvants in modern viral vaccine technology and their influence on
      the immune system are the subject of this review.

PMID- 9554257
TI  - Iscom, a delivery system for parenteral and mucosal vaccination.
AB  - The iscom is a supramolecular spherical structure, about 40nm in diameter, built
      up by structure-forming and immunomodulating quillaja triterpenoids, lipids and
      antigens. Iscoms with a defined quillaja triterpenoid formulation named QH 703
      are in human trials. The advantages of using the particulate iscom form of
      quillaja components are (i) that local reactions at the site of injection can be
      avoided; a manifold higher dose of quillaja components in iscoms than in free
      form can be injected without causing side effects; (ii) considerably lower doses
      of both quillaja components and antigens are required to obtain a certain level
      of immune response. The iscom particle targets the antigen and adjuvant
      components to both the endosomal and cytosolic pathways for antigen presentation,
      resulting in both MHC class I and class II restricted immune responses. Further,
      iscoms induce APC to produce IL-1, IL-6 and IL-12 and a TH1 type of response with
      enhanced IL-2 and IFN-gamma production. Iscoms are now constructed to target the
      mucosal lymphatic systems. Iscoms administered intranasally induce secretory IgA
      responses in lungs and distant mucosal membranes e.g. in the genital tract.

PMID- 9554258
TI  - QS-21 and QS-7: purified saponin adjuvants.
AB  - QS-21 and QS-7 are two adjuvant-active saponins that can be obtained in high
      purity from Quillaja saponaria Molina extracts. QS-21 is a highly characterized
      compound and is known to be a potent adjuvant for antibody and CD8+ CTL response
      to subunit antigens. Less is known about the activity and structure of the
      hydrophilic saponin QS-7. Hence, we have carried out a detailed structural and
      immunological characterization. As with QS-21, QS-7 was shown to be a 3,28-O
      bisglycoside quillaic acid, with some differences being a higher degree of
      glycosylation and a considerably shorter fatty acyl unit in QS-7. These
      differences were correlated to a lower lytic activity against sheep red blood
      cells. Different doses of QS-7 were evaluated for stimulation of immune response
      to the antigen ovalbumin, given three times by subcutaneous route to C57BL/6
      mice. QS-7 doses of 40 micrograms or higher were shown to induce a strong CD8+
      CTL response reproducibly against E. G7-OVA targets (similar to that induced by a
      5-10 micrograms dose of QS-21). QS-7 (at doses above 5 micrograms) was also shown
      to stimulate CTL against peptide 18 of HIV-1IIIB gp120 after three immunizations
      of Balb/c mice with recombinant gp120 and different doses of QS-7. These data
      suggest that a hydrophilic saponin with low lytic activity can stimulate MHC
      Class I CTL responses although a higher minimum dose may be required for some
      antigens.

PMID- 9554259
TI  - Induction of virus-specific immunity by iscoms.
AB  - Immune stimulating complexes (iscoms) are 30-40 nm cage-like structures, which
      consist of glycoside molecules of the adjuvant Quil A, cholesterol and
      phospholipids in which antigen can be integrated. Even in the presence of pre
      existing antibodies they may function as a potent adjuvant system by inducing
      high systemic and local long-lasting antibody and T cell responses. An additional
      advantage is their capacity to induce MHC class I restricted CD8+ CTL responses.
      This combination will in most cases, when the relevant antigens are incorporated,
      lead to adequate protection against virus infection or disease. An overview is
      given of the present data available on the use of iscoms in viral systems, and
      some relevant examples are discussed to highlight general principles in the use
      of iscoms as an adjuvant system.

PMID- 9554260
TI  - Biodegradable polymer microspheres as vaccine adjuvants and delivery systems.
AB  - Though vaccination has been the most cost-effective way of controlling infectious
      diseases, the logistics of delivering at least two to three doses of conventional
      vaccines for primary immunization to achieve protection are difficult and
      compliance is frequently inadequate, particularly in developing countries. In
      recent years biodegradable polymer microspheres have received much attention for
      the purposes of controlled release of antigens, (i) to reduce the number of doses
      needed for primary immunization to as few as a single dose and (ii) to target an
      antigen to microfold cells on mucosal surfaces after oral administration or to
      antigen-presenting cells after parenteral inoculations. A variety of vaccine
      antigens have been encapsulated in microspheres usually composed of poly
      (lactic/glycolic) acid (PLGA). Based on the size of the microspheres, molecular
      weight of polymer and ratio of lactic to glycolic acid in the polymer, the
      antigen may be targeted to various cells of the immune system or it may form a
      depot at the site of injection, allowing the slow release of the antigen for
      extended periods. Additionally, another adjuvant may be incorporated inside
      microspheres together with the antigen, further enhancing or modulating the
      immune response to the desired type. The major problems in developing controlled
      release vaccines include instability of vaccine antigens during micro
      encapsulation, storage and subsequent hydration. We encapsulated tetanus toxoid
      (TT) and Haemophilus influenzae type b capsular polysaccharide conjugated to TT
      (Hib-T) inside PLGA microspheres and evaluated the antibody levels in mice. A
      single injection of these micro-encapsulated vaccines elicited high antibody
      levels which persisted for several months. The antibody levels were similar or
      superior to those elicited by conventional formulations of AIPO4-adsorbed TT or
      soluble Hib-T conjugate vaccine.

PMID- 9554262
TI  - Cellular and molecular mechanisms for induction of mucosal immunity.
AB  - The epithelial glycoprotein called secretory component (SC) is quantitatively the
      most important receptor of the immune system because it is responsible for
      external transport of locally produced polymeric IgA (pIgA) to generate
      remarkably large amounts of secretory IgA. Antibodies of this type constitute the
      major mediators of specific humoral immunity. Transmembrane SC belongs to the Ig
      supergene family and functions as a common pIg receptor, also translocating
      pentameric IgM externally to form secretory IgM. The B cells responsible for
      mucosal production of Ig polymers are initially stimulated in organized mucosa
      associated lympho-epithelial structures, particularly the Peyer's patches in the
      distal small intestine; from these inductive sites they migrate ("home") as
      memory cells to exocrine tissues all over the body. Mucous membranes are thus
      furnished with secretory antibodies in an integrated way, ensuring a variety of
      specificities at every secretory effector site. There is currently great interest
      in exploiting this integrated or "common" mucosal immune system for oral
      vaccination against pathogenic infectious agents and also to induce tolerance in
      T cell-mediated auto-immune diseases. However, much remains to be learned about
      mechanisms for antigen uptake and processing necessary to elicit stimulatory or
      suppressive mucosal immune responses in humans. Moreover, evidence is emerging
      for the existence of considerable regionalization with regard to functional links
      between inductive sites and effector sites of mucosal immunity.

PMID- 9554261
TI  - PCPP as a parenteral adjuvant for diverse antigens.
AB  - The adjuvanticity of the phosphazene polymer, poly[di(carboxylatophenoxy)
      phosphazene] (PCPP) was examined with a diverse collection of immunogens. PCPP
      proved to be a potent adjuvant for trivalent influenza virus vaccine, tetanus
      toxoid, hepatitis B surface antigen, herpes simplex virus glycoprotein gD2 and
      the capsular polysaccharide, polyribosylribitolphosphate, from Haemophilus
      influenzae type b. Taken together these results clearly demonstrate the general
      utility of PCPP as an adjuvant. Furthermore, PCPP was a superior adjuvant at
      least with TT compared to similar negatively charged polyanions,
      polymethylacrylic acid and polyacrylic acid.

PMID- 9554263
TI  - Lipidation as a novel approach to mucosal immunization.
AB  - We describe the design and development of a novel peptide-based approach for
      mucosal immunization. The design contains an amplified peptide chain as multiple
      antigen peptide (MAP) with a cluster of lipids. Such a design would confer on
      lipidated MAP the ability to self-assemble in water, mimicking enveloped viral
      particles. The importance of lipidation for mucosal immunization was confirmed by
      oral immunization with lipidated MAP in phosphate-buffered saline (PBS), which
      induced mucosal and systemic immune responses at local and distant sites,
      including sera and vaginal IgG as well as secretory IgA in saliva, vaginal
      secretions and fecal matter. T-cell proliferative responses were found in spleen,
      Peyer's patches and genital lymph nodes. In addition, significant splenic
      cytotoxic T-cell responses were also observed. No significant immune responses
      were observed with non-lipidated MAPs by oral delivery in PBS. Furthermore, these
      responses were selectively enhanced by different regimens, systemic priming and
      microparticle delivery. These results demonstrate the effectiveness of lipidated
      MAP for mucosal immunization to evoke both systemic and mucosal immune responses
      without the use of carrier or extraneous adjuvant.

PMID- 9554264
TI  - Systemic immunization with conserved pilus-associated adhesins protects against
      mucosal infections.
AB  - Colonization and infection of the bladder mucosa by Escherichia coli, the major
      uropathogenic organism, is dependent on the expression of pilus organelles. Type
      1 pili are expressed by the majority of E. coli strains derived from patients
      with cystitis and pyelonephritis. FimH is the adhesin protein located at the
      distal tip of the heteropolymeric type-1 pilus which mediates binding to bladder
      cells through mannose receptors. We have shown that humoral antibody raised
      against two forms of purified FimH adhesin inhibited 94% (49/52) of E. coli UTI
      clinical isolates from binding to bladder tissue in vitro. Animals immunized with
      FimH-containing vaccines by a systemic route reduced colonization of the bladder
      mucosa in vivo in a murine cystitis model by > 99%. IgG antibody to FimH was
      detected in urinary samples obtained from immunized, protected mice. Passive
      systemic administration of immune sera from FimH-inoculated mice to naive animals
      also resulted in reduced colonization of bladder mucosa by uropathogenic E. coli.
      These studies demonstrate that systemic immunization with an anti-bacterial
      vaccine targeting a highly conserved adhesin on uropathogenic E. coli can induce
      IgG-mediated protection at a mucosal surface and may be a means of preventing
      recurrent and acute infections of the urogenital tract mucosa.

PMID- 9554265
TI  - Adjuvant effect of non-toxic mutants of E. coli heat-labile enterotoxin following
      intranasal, oral and intravaginal immunization.
AB  - Cholera toxin and Escherichia coli heat-labile enterotoxin (LT) are known to be
      very effective mucosal adjuvants, but their toxicity limits their use in humans.
      We genetically detoxified LT by substituting single residues in the active site
      of the enzymatic A subunit and obtained mutant molecules that retain mucosal
      adjuvant activity but are devoid of toxicity. These mutant LT molecules induce
      mucosal and systemic responses to antigens delivered intranasally, orally and
      intravaginally in mice. Furthermore, mucosal immunization with these molecules
      confers protection against systemic challenge with tetanus toxin (TT) and mucosal
      challenge with Helicobacter pylori.

PMID- 9554266
TI  - Towards a nasal vaccine against meningococcal disease, and prospects for its use
      as a mucosal adjuvant.
AB  - A Norwegian outer membrane vesicle (OMV) vaccine against group B meningococcal
      disease proved to be strongly immunogenic when administered intranasally in mice.
      The OMV preparation, made from Neisseria meningitidis and intended for parenteral
      use, was therefore given without adjuvant to human volunteers (n = 12) in the
      form of nose drops or nasal spray. Such immunizations, which were carried out at
      weekly intervals during a three-week period, were able to induce systemic
      antibodies with bactericidal activity in more than half of the individuals. In
      addition, all vaccinees developed marked increases in OMV-specific IgA antibodies
      in nasal secretions. The potential of the OMV particles as carriers for other
      less immunogenic antigens were elucidated in mice with use of whole inactivated
      influenza virus. Even though influenza virus alone did induce some systemic and
      salivary antibody responses after being administered intranasally, these
      responses were greatly augmented when the virus was presented together with OMVs.
      Thus, it is possible that a nasal OMV vaccine may induce protection against
      invasive meningococcal disease, and also that it might be used as a vehicle for
      nasal vaccines against other diseases.

PMID- 9554267
TI  - The potential of retro-inverso peptides as synthetic vaccines.
AB  - Retro-inverso (RI) peptides, also called all-D-retro peptides, have been shown to
      mimic the antigenic and immunogenic properties of L-peptides successfully. RI
      peptides corresponding to the loop 141-159 of the VP1 protein of foot-and-mouth
      disease virus (FMDV) have been synthesized and used to immunize rabbits and
      guinea pigs. These peptides induced longer-lasting and higher antibody titres in
      immunized animals than did the corresponding L-peptides and the antibodies cross
      reacted strongly with virus particles and with L-peptides. Antisera raised to RI
      peptides had in vitro virus neutralization titres equal to or better than those
      obtained after immunization with classical FMDV antigens and L-peptides. In view
      of their increased stability, RI peptides may overcome some of the shortcomings
      of synthetic viral vaccines based on L-peptides.

PMID- 9554268
TI  - Protective immunity to intracellular parasites--a focus for vaccine research and
      a challenge to immunization programmes.
AB  - Protective immunity to intracellular parasites is mediated by T cells. This
      response is complex, requiring activation of several subgroups of T cells and
      production of a balanced blend of cytokines to obtain protection rather than
      delayed hypersensitivity leading to tissue damage. To obtain additional, detailed
      information, on the kind, proper localization and specificity of the required
      immune response represents a major challenge in current vaccine research.
      Insufficient knowledge of these features is the major constraint for development
      as illustrated in tuberculosis and related mycobacterial infections.

PMID- 9554269
TI  - Oral delivery of micro-encapsulated DNA vaccines.
AB  - Oral delivery of vaccines is an attractive alternative to injection. It is a non
      invasive procedure which allows access to the gut-associated lymphoid tissues
      (GALT). Immunisation at GALT results in mucosal immune responses, which may be of
      particular importance in protection against infection at mucosal surfaces, as
      well as systemic immune responses. Vaccine antigens can be protected in the gut
      by encapsulation in poly(DL-lactide-co-glycolide) (PLG) microparticles. Their
      uptake into the immune inductive tissues of the GALT is mediated by M cells,
      which selectively phagocytose particles less than 10 microns in diameter. We have
      developed a method for the PLG encapsulation of plasmid DNA. Encapsulated DNA,
      expressing the insect protein luciferase under the transcriptional control of the
      human cytomegalovirus immediate early promoter, was administered to mice by
      intraperitoneal injection or oral gavage. Intraperitoneal injection of
      encapsulated DNA elicited good serum IgG and IgM responses and a modest IgA
      response. Oral administration stimulated good serum antibody titres in all three
      classes, and in addition, significant levels of mucosal IgA. PLG encapsulation
      thus has the ability to protect plasmid DNA against degradation after
      administration, and to facilitate its uptake into appropriate cells for the
      subsequent expression and presentation of antigen, in such a way as to elicit
      both systemic and mucosal antibody responses. This may have major implications
      for the design of novel vaccines and delivery strategies.

PMID- 9554270
TI  - Nucleic acid vaccines against hepatitis viruses.
AB  - Direct DNA intramuscular or intradermal injection of plasmids containing viral
      genes under the control of viral promoters is an efficient means of stimulating
      both class I and class II-mediated antiviral responses. Viral hepatitis B and C
      are suitable candidates for this approach, particularly as therapeutic immunogens
      for chronically infected individuals. Several groups have shown that the S gene
      of HBV is expressed in murine muscle and stimulates a high titre and long-lasting
      anti-HBs response. Uniquely, CD8+ CTL responses are also induced to HBsAg. No
      vaccine exists for HCV. Therefore the structural genes (C + E1 + E2) have been
      cloned as a 2,831 bp fragment from a genotype la isolate into the vector pcDNA3.
      The resulting plasmid DNA was injected directly into the quadriceps muscle of
      three-week-old BALB/c mice. Intracellular-expressed E1 and E2 proteins thus
      represent the complete spectrum of native structural epitopes, including those
      dependent on glycosylation and protein folding. Mouse antisera were tested for
      reactivity against conserved sequences using overlapping 7-mer peptides. Two
      conserved, overlapping epitopes were identified in E2 spanning residues 581-591
      and 590-603. This domain represents one of seven major E2 antigenic domains
      recognized by HCV human antibodies, one of three with antigenic homologies to
      related flavivirus proteins. Thus antigen is presented with high efficiency
      following DNA injection and offers the potential of high rates of seroconversion
      and virus clearance in those predisposed to virus-induced chronic liver disease.

PMID- 9554271
TI  - Immune responses against hepatitis C virus structural proteins following genetic
      immunisation.
AB  - We have used direct DNA inoculation to study the in vivo induction of both
      humoral and cellular immune responses to hepatitis C virus (HCV) encoded
      structural antigens. Following immunisation of mice, immune responses were
      compared using plasmids encoding full-length or partial HCV gene sequences for
      the nucleocapsid and envelope E2 proteins. Plasmids encoding secreted or non
      secreted forms of the immunogens, including constructs expressing HCV sequences
      fused with the hepatitis B virus surface antigen (HCV-HBV chimeras), were
      evaluated. Results indicate that: (i) all constructs induced specific anti-HCV
      antibodies; (ii) antibody titres ranged from 1:100 to > 1:100,000; (iii) all HCV
      DNA immunogens induced a predominant Th1 response with the induction of IgG2a
      antibodies; (iv) the secretion level of the antigens and immune responses was not
      always correlated and (v) CTL could be detected against both HCV and HBV
      determinants.

PMID- 9554272
TI  - Induction of a TH1 type cellular immune response to the human immunodeficiency
      type 1 virus by in vivo DNA inoculation.
AB  - DNA inoculation is capable of producing antigens intracellularly for ultimate
      presentation to the cellular and humoral components of the immune system and has
      potential for vaccine strategies against a number of infectious pathogens
      including HIV-1. It is well documented that the antigenic diversity of HIV-1 and
      its high level of nucleotide mutations during reverse transcription can lead to
      escape from immune surveillance. However, data suggest that a CD8-mediated
      cytotoxic T lymphocyte response may be less susceptible to escape mutants. We
      have shown previously that in vivo inoculation of rodents and non-human primates
      with plasmid expression vectors encoding HIV-1 gene products leads to production
      of HIV-1 antigens and results in the production of both cellular and humoral
      immune responses. In addition we have also demonstrated previously that these
      responses lead to protection in several in vivo models. We further demonstrate
      here that the cellular response induced is a type TH1 response and specific lysis
      of HIV-infected targets is CD8-mediated.

PMID- 9554274
TI  - Antigen-independent activation of resting T-cells in the liver of patients with
      chronic hepatitis.
AB  - Since the adult liver is an organ without constitutive lymphoid components, any
      intra-hepatic T cell found in chronic viral hepatitis should have
      compartmentalised to the liver after infection and inflammation. In liver
      biopsies from patients with chronic hepatitis C there is a great discrepancy
      between the percentage of activated T cells and the frequency of antigen-specific
      T cells. Usually, 40 to 80% of the liver-infiltrating T cells express activation
      markers, whereas only 0.5%, at best, of these cells are specific for any HCV
      protein. This finding suggests that there may be antigen independent mechanisms
      activating bystander T cells. We investigated whether human resting T cells could
      be activated to proliferate and display effector function in the absence of TcR
      occupancy. We have found that a combination of IL-2, TNF alpha and IL-6 could
      activate highly purified naive and memory T cells to proliferate. Under these
      conditions, resting memory T cells could also display effector function, as
      assessed by cytokine synthesis and help for IgG production by B cells. This novel
      antigen-independent pathway of T cell activation may play an important role in
      vivo in activating effector T cells in the liver and in maintaining the clonal
      size of peripheral memory T cells in the absence of antigenic stimulation.

PMID- 9554273
TI  - The effect of IL-12 treatment on vaccine-enhanced illness during infection with
      respiratory syncytial virus.
AB  - In humans and mice, sensitisation to respiratory syncytial virus (RSV) antigens
      can result in severe inflammatory lung disease during subsequent infection with
      the virus. Although specific antiviral T cells are thought to be responsible for
      this augmentation of disease, the precise role of different functional subsets is
      unknown. BALB/c mice sensitised to the major surface glycoprotein (G) of RSV
      expressed by recombinant vaccinia virus develop Th2-driven lung eosinophilia
      after intranasal challenge with the virus. Mice treated with IL-12 at various
      times during vaccination and challenge, had reduced vaccine-induced lung
      eosinophilia but increased total pulmonary lymphoid cell infiltration.
      Intracellular cytokine analysis showed that interferon-gamma production during
      challenge was increased and IL-4 and IL-5 reduced by IL-12 treatment. Though IL
      12 treatment reduced lung eosinophilia, illness (as assessed by weight loss) was
      not eliminated and sometimes increased. Reversing Th2-associated pathology with
      IL-12 does not necessarily benefit the host.

PMID- 9554275
TI  - A novel method for enhancement of T independent responses.
AB  - Bacterial capsular polysaccharides are the major targets for vaccination against
      encapsulated bacteria but present problems when used for immunisation as they are
      T cell independent antigens (TI-II). TI-II antigens do not induce a memory
      response, but induce an antibody response which is of low magnitude and is
      predominantly IgM, with little or no isotype switching to IgG isotypes. This is
      because TI-II antigens do not induce T cell help. Such T cell help to B cells is
      mediated through up regulation of the CD40 ligand (CD154) on the activated T
      cell, which binds to CD40 inducing B cell activation, proliferation and isotype
      switching in conjunction with cytokines produced by the T cell. We have
      successfully mimicked this T cell help and induced very strong, isotype switched
      antibody responses to TI-II antigens by the simple addition of agonistic anti
      CD40 antibodies to pneumococcal polysaccharides before immunisation.

PMID- 9554276
TI  - Cytotoxic activity induced by Mycobacterium Bovis BCG.

PMID- 9554277
TI  - The role of cytotoxic T-cells in HIV infection.
AB  - HIV-specific cytotoxic T lymphocytes (CTL) are believed to play a major role in
      controlling virus levels through the asymptomatic period of HIV infection. For
      the rational design of an HIV vaccine, we need to know whether protective
      immunity can ever develop following HIV exposure in people who remain uninfected.
      We have detected HIV-specific CTL in 5/6 repeatedly exposed, persistently
      seronegative female sex-workers in The Gambia. Their CTL, repeatedly detected
      over two years, recognise epitopes presented by HLA-B35 which are cross-reactive
      between HIV-1 & HIV-2, suggesting they could have been primed first by HIV-2
      exposure and subsequently boosted by exposure to HIV-1. Using previously
      identified clade B HIV-1 epitope peptides, we have now detected HIV-specific CTL
      in 6/15 highly exposed and apparently HIV-resistant Kenyan prostitutes,
      predominantly towards epitopes highly conserved between B and the Kenyan A & D
      clades of HIV-1. This CTL activity towards conserved virus epitopes may represent
      protective immunity to HIV generated in response to repeated exposure, and
      prophylactic HIV vaccines should aim to generate similar CTL responses.

PMID- 9554278
TI  - Immunopotentiating reconstituted influenza virosomes as a novel antigen delivery
      system.
AB  - Using immunopotentiating, reconstituted influenza virosomes (IRIV) as a delivery
      vehicle, a number of vaccines have been developed. In humans, IRIV-based vaccines
      containing hepatitis A and influenza antigens have been found to possess enhanced
      immunogenicity compared to alum-adsorbed vaccine for hepatitis A or commercial
      subunits or whole virion influenza vaccines. These vaccines were safe and did not
      engender any anti-phospholipid antibodies against the liposome components of the
      IRIV. Hepatitis B, tetanus toxoid and diphtheria toxoid, and nucleic acids have
      also been incorporated into IRIVs. These vaccines are now undergoing clinical
      phase I testing. IRIVs are also being evaluated in phase I trials for their
      ability to deliver antigens by the intranasal route.

PMID- 9554279
TI  - Protective mucosal immunity elicited by targeted lymph node immunization with a
      subunit SIV envelope and core vaccine in macaques.
AB  - Prevention of sexually transmitted HIV infection was first investigated in non
      human primates by mucosal immunization via the rectal, vaginal or male urethral
      route. This was compared with subcutaneous targeted iliac lymph node (TILN) and
      systemic intramuscular immunization in non-human primates. TILN immunization
      elicited the most consistent mucosal sIgA and IgG antibody response in the
      rectum, vagina, urine and seminal fluid, as well as in blood. Both mucosal and
      TILN immunization induced a specific CD4+ T cell proliferative response in the
      iliac lymph nodes which drain these mucosal surfaces, and in the splenic and
      circulating T cells. In the next experiment macaques were immunized by the TILN
      route with SIV gp120 and p27 in alum. Rectal mucosal challenge with SIVmac 32H J5
      molecular clone (or cell-free virus) induced total protection in four out of
      seven macaques, compared with infection in 13 of 14 unimmunized macaques or
      immunized by other routes (p = 0.025). The remaining three macaques immunized by
      the TILN route showed either decrease in viral load (> 90%) or transient
      viraemia, indicating that all seven TILN immunized macaques showed total or
      partial protection of rectal transmission by SIV (p = 0.001). Protection was
      associated with significant increase in the iliac lymph nodes IgA antibody
      secreting cells to p27 (p < 0.02), CD8-suppressor factor inhibiting replication
      of SIV in CD4+ T cells (p < 0.01) and the chemokines RANTES and MIP-1 beta (p <
      0.01). We suggest that administration of gp120 and p27 by the TILN route may
      elicit protective B and T cell immunity which can significantly prevent rectal
      transmission of SIV or HIV.

PMID- 9554280
TI  - Adjuvants in perspective.
AB  - Many vaccines currently under development and testing are composed of synthetic,
      recombinant, or highly purified subunit antigens. Vaccines composed of these
      subunit antigens are often considered to be safer than whole-inactivated or live
      attenuated vaccines. However, vaccines containing purified subunit antigens are
      often less immunogenic than traditional vaccines. Immunological adjuvants are
      agents that enhance specific immune responses to vaccines. Formulation of
      vaccines with potent adjuvants is an attractive approach for enhancing immune
      responses to subunit antigens. Adjuvants have diverse mechanisms of action and
      should be selected for use based on the route of administration and the type of
      immune response (antibody, cell-mediated, or mucosal) desired for a particular
      vaccine. Adjuvant mechanisms of action include: (i) increasing the biological or
      immunological half-life of vaccine antigens; (ii) improving antigen delivery and
      presentation; and (iii) inducing the production of immunomodulatory cytokines.
      Through modulation of cytokine responses, adjuvant formulations can be designed
      that favour the development of Th1 (type 1) or Th2 (type 2) immune responses to
      vaccine antigens. Novel adjuvants are currently undergoing preclinical and
      clinical testing with experimental vaccines, including vaccines against HIV-1.
      Standardized preclinical adjuvant safety tests are also being developed.

PMID- 9554281
TI  - Modulation of the immune response to tetanus toxoid by polylactide-polyglycolide
      microspheres.
AB  - The cellular and antibody responses in mice to tetanus toxoid (TT), alone or
      adsorbed to aluminium hydroxide TT were compared to those obtained with TT
      incorporated in polylactide-polyglycolide (PLGA) microspheres, a candidate single
      dose vaccine. After subcutaneous injection, the serum IgM antibody to TT followed
      similar overall patterns for all preparations although the highest levels were
      achieved with the alum-adsorbed material. A similar pattern was observed with the
      overall IgG antibody responses. The isotype distribution of antibodies was
      broadly similar for all types of preparation although considerable qualitative
      differences were observed. IgG1 antibodies predominated although IgG2a and IgG2b
      made a substantial contribution, especially at three months in the case of the
      two adjuvanted preparations. The IgG3 responses to each type of vaccine were very
      low. Both alum and microsphere vaccines induced proliferative responses to TT in
      splenic lymphocytes at three months after vaccination. Each type of vaccine was
      much less effective in inducing proliferative responses in lymph node cells.
      There was evidence of induction of IL2, IL4 and interferon-gamma genes by
      microsphere vaccines in splenic but not lymph node cells. There were indications
      that PLGA microspheres alone exerted a modulating effect on cellular responses
      after immunization. These results suggest that TT encapsulated in microspheres
      induces a pattern of cellular and antibody responses qualitatively similar to
      those induced by conventional TT vaccines.

PMID- 9554282
TI  - Development of an animal model to assess the immunogenicity of single-dose
      tetanus and diphtheria vaccines based on controlled release from biodegradable
      polymer microspheres.
AB  - We have determined threshold doses of aluminium phosphate (AlPO4) adsorbed
      tetanus toxoid (TT) and diphtheria toxoid (DT) in mice and guinea pigs with a
      view to developing an animal model to assess the immunogenicity of controlled
      release vaccines. A dose was sought (threshold dose) which produces little
      antibody after primary injection and a moderate response after a booster
      injection, thus mimicking the adult human response to TT and DT vaccines adsorbed
      on to aluminium adjuvants. After the first injection, mice and guinea pigs showed
      a dose response for both tetanus toxin IgG antibodies and tetanus antitoxin over
      a wide range of doses of AlPO4-adsorbed TT (0.01 to 0.2 Lf). After the second and
      third injections, there was no clear dose response for doses between 0.05 and 0.2
      Lf However, doses between 0.01 and 0.04 Lf still showed a dose response after the
      second injection. Dilution of AlPO4-adsorbed TT in saline just before injection
      did not alter immunogenicity after the first injection, but stronger booster
      responses were seen in mice to diluted versus undiluted vaccine after the second
      and third injections. The threshold dose of AlPO4-adsorbed TT for both mice and
      guinea pigs was 0.01 Lf given in 100 microliters. For AlPO4-adsorbed DT, three
      strains of mice (inbred, Balb/c and C57/B6, and outbred, CD-1) showed a dose
      response after the first injection for DT IgG antibodies and diphtheria antitoxin
      at 0.1 and 0.2 Lf doses. Outbred CD-1 mice showed a dose response after the
      second and third injections also, whereas inbred mice showed inconsistent dose
      responses after the second injection and none after the third injection. In
      contrast to AlPO4-adsorbed TT, mice injected with undiluted AlPO4-adsorbed DT
      elicited significantly higher antibodies than those injected with diluted
      formulations, particularly after the first injection. The threshold dose of AlPO4
      adsorbed DT for mice was 0.1 Lf in a volume of 250 microliters. Lower doses did
      not produce consistent antibody responses in mice. We propose that a single dose
      of controlled release formulations at doses not greater than 1/10 of a single
      human dose when injected into mice and guinea pigs should produce an antibody
      response similar or higher than two to three threshold doses of AlPO4-adsorbed TT
      or DT.

PMID- 9554283
TI  - Kinetics, localization and characteristics of B- and T-cell responses to iscoms
      containing human influenza virus glycoproteins.
AB  - B- and T-cell responses have been studied after primary and secondary
      immunizations of mice with iscoms containing influenza virus envelope
      glycoproteins. After primary immunization both B- and T-cell responses were
      initiated in the draining lymph nodes. T-cells showed peak activity with respect
      to proliferation and cytokine production after five to eight days and the highest
      number of IgG secreting cells (IgG-SC) was recorded at day seven. The responses
      in the spleen developed slowly but were of longer duration. Cytokines produced by
      spleen cells included high levels of IFN-gamma and IL-2. After a secondary
      immunization the frequencies of IgG-SC were drastically increased in both LN and
      spleen, but decreased rapidly with time. At day eight after the secondary
      immunization high numbers of IgG-SC were detected in the bone marrow. High titres
      of IgG1 and IgG2a and substantial titres of IgG2b and IgG3 were detected in
      serum.

PMID- 9554284
TI  - In vitro determination of antigen quality: biosensor analysis and fluorescence
      spectroscopy.
AB  - We are probing the potential of two techniques to monitor the quality of antigens
      in vitro. Structural and conformational differences between diphtheria toxin and
      toxoid are detected via biosensor analysis (BIA-core) and fluorescence
      spectrometry. With BIA-core the interaction kinetics between toxin and toxoid and
      a monoclonal antibody were established. The fluorescence properties of both
      antigens were determined with respect to fluorescence intensity and emission
      maximum as a function of guanidinium hydrochloride concentration. In all cases
      clear differences were found between toxin and toxoid. Antibody affinity of the
      toxoid was lower compared with toxin, caused by lower binding and higher release
      rates. Fluorescence intensity of toxoid was reduced by about 50%. Toxoid was less
      sensitive to guanidinium hydrochloride-induced denaturation, reflected in a
      diminished shift of the emission maximum.

PMID- 9554285
TI  - Immunity provided by haemorrhagic septicaemia-subunit vaccine in ruminants.
AB  - A subunit vaccine against haemorrhagic septicaemia (HS), the principal killer
      disease in ruminants, especially cattle and carabao, in the Philippines, has been
      developed. Using capsules of Pasteurella multocida Group B as an active component
      of the vaccine, it gave solid protection against challenge with live organism in
      mice. An active calf protection test showed that in 24 hours, animals vaccinated
      with plain saline died after challenge compared to those given the subunit
      vaccine which survive the challenge dose. Using 104 cattle from a farm, the field
      trial of the HS subunit vaccine showed that the antibody titre was high for up to
      14 months. A high titer is an indication of protection.

PMID- 9554286
TI  - Cellular immune responses of cattle to Cowdria ruminantium.
AB  - Peripheral blood mononuclear cells (PBM) from cattle immunised against Cowdria
      ruminantium infection (Heartwater), proliferated in vitro in the presence of
      either infected autologous endothelial cells pre-treated with T cell growth
      factors to induce MHC class II expression, or infected autologous monocytes.
      Proliferation was not observed in PBM cultured with a soluble extract of the
      agent, but PBM responded to two recombinant antigens of C. ruminantium, namely a
      32 kDa (MAP1) and a 21 kDa antigen (MAP2). We hypothesize that infected
      endothelial cells and monocytes present Cowdria antigens to specific lymphocytes
      during infection and thereby play a role in the pathogenesis/immune response to
      the pathogen.

PMID- 9554287
TI  - Salivary immune responses after gingival immunization with tetravaccinal and
      bivaccinal formulations of inactivated micro-organisms.
AB  - Two groups of rats were treated separately, fourteen times during three months,
      by rubbing at gingival mucosa with two antigenic mixtures: (i) Staph. aureus,
      Str. faecalis, E. coli and Prot. vulgaris; (ii) Str. mutans and Act. viscosus. At
      the end of the treatments the increases of specific salivary IgAGM ranged from
      202.6% (Str. faecalis) to 312.7% (E. coli) in the case of tetravaccinal
      association and from 123% (Act. viscosus) to 171.4% (Str. mutans) in the one of
      bivaccinal formulation.

PMID- 9554289
TI  - Humoral response to HSV-1 subunit vaccines--a statistical analysis.
AB  - Following primary infection with HSV, the virus becomes latent in the local
      sensory ganglia for the lifetime of the host. In some cases, periodic
      reactivation may occur due to various stimuli and cause a recrudescent lesion at
      or near the initial site of infection. As yet there is no suitable vaccine to
      prevent its spread within the human population. We investigated the potential of
      a large number of commercial and experimental adjuvant preparations to enhance
      the immunogenicity of an HSV-1 glycoprotein subunit vaccine. Evaluation was based
      on toxicity, total antibody titre, neutralizing antibody production and
      protection against lethal challenge. All adjuvants tested increased the titre of
      antigen specific total and neutralizing lg when compared to subunit vaccine
      alone, although functional neutralising antibody was only detected in some cases.
      Following challenge, a broad range of protective responses was noted but no
      correlation between antibody levels and protection was observed. The results
      emphasize the requirement of adjuvants when using subunit preparations as vaccine
      formulations and demonstrate that the magnitude and effectiveness of the induced
      immune response varies greatly with the choice of adjuvant.

PMID- 9554290
TI  - Systematic development of a block copolymer adjuvant for trivalent influenza
      virus vaccine.
AB  - The current influenza virus vaccines induce systemic humoral immunity and short
      lived cellular immunity in young adults. Unfortunately these vaccines are only
      50% efficacious in the elderly (> 65 years) and high risk groups of the very
      young. The use of a vaccine adjuvant to correct this deficit would therefore be
      very beneficial to these population groups. We have developed high molecular
      weight synthetic non-ionic block copolymers with adjuvant activity. These
      copolymers are compatible with, and active in, aqueous, physiological
      formulations in which they spontaneously assemble into 500-3000 nm particles. By
      varying both the molecular weight and the proportions of hydrophilic and
      hydrophobic components of the molecule, we have designed the optimal copolymer
      adjuvant for use with influenza hemagglutinin. This copolymer, termed CRL-1005,
      was investigated for its ability to augment the immune response of mice to the
      commercially-available human influenza vaccine, Fluogen. Co-formulation of CRL
      1005 with the vaccine resulted in markedly increased antibody titres measured by
      both ELISA and the functional haemagglutination inhibition assay, indicating that
      critical immunogen epitopes were not destroyed. A single dose of copolymer and
      vaccine produced both long term rising antibody titres (six months) and primed
      for a potent secondary response. This high molecular weight copolymer is non
      toxic and should therefore be well suited for widespread use.

PMID- 9554288
TI  - Effect of aluminium hydroxide and meningococcal serogroup C capsular
      polysaccharide on the immunogenicity and reactogenicity of a group B Neisseria
      meningitidis outer membrane vesicle vaccine.
AB  - Three different formulations of an outer membrane vesicle (OMV) vaccine against
      group B meningococcal disease have been prepared and tested for immunogenicity
      and reactogenicity in adult volunteers. The vaccines were prepared with or
      without aluminium hydroxide and serogroup C-polysaccharide (C-ps). Doses from
      12.5 to 100 micrograms protein were given twice at a six weeks' interval. All
      three formulations were well tolerated and highly immunogenic, inducing
      bactericidal and opsonizing antibodies in humans. Adsorption of OMVs to aluminium
      hydroxide reduced the pyrogenicity in rabbits. The differences in immunogenicity
      between the formulations were relatively small, but after the second dose a
      stronger booster response was observed when the vaccines were adsorbed. Thus, a
      formulation with OMVs and C-ps represents a safe and highly immunogenic vaccine,
      even without aluminium hydroxide.

PMID- 9554291
TI  - Ovalbumin coupled either with murine red blood cells or liposome induces IgG but
      not IgE antibody production.
AB  - Ovalbumin (OVA) was coupled with murine red blood cells (MRBC) using
      glutaraldehyde. The OVA-MRBC conjugate induced anti-OVA IgG antibody in mice at
      almost the same level as OVA in alum. However, no IgE antibody production
      specific for OVA was observed in OVA-MRBC-injected mice. A significant increase
      in IGG2a production was obtained with OVA-MRBC immunization, whereas the
      production of IgG1 predominated in OVA in alum immunization. Am OVA-liposome
      conjugate induced IgE-specific unresponsiveness in mice in the same manner as OVA
      MRBC. Similar results were obtained when antigens other than OVA, such as tetanus
      toxoid or diphtheria toxoid, were coupled to liposome. These results show the
      potential of antigen-liposome conjugates for the development of vaccine that
      induces sufficient IgG antibody production without IgE synthesis.

PMID- 9554292
TI  - Scleredema of Buschke successfully treated with electron beam therapy.

PMID- 9554293
TI  - An infant with firm, fixed plaques.

PMID- 9554294
TI  - The morality of cosmetic surgery for aging.

PMID- 9554295
TI  - Clinical, pathologic, and immunologic features of human T-lymphotrophic virus
      type I-associated infective dermatitis in children.
AB  - OBJECTIVES: To define the clinical and laboratory features associated with
      infective dermatitis (ID) and confirm its association with human T-lymphotrophic
      virus type I (HTLV-I). DESIGN: A case series of patients with ID were compared
      with patients with atopic dermatitis (AD), which is an important disease in the
      differential diagnosis of ID. SETTING: Patients were recruited from dermatology
      and pediatric clinics at the University Hospital of the West Indies and the
      Bustamante Children's Hospital, Kingston, Jamaica. MAIN OUTCOME MEASURES:
      Clinical and laboratory features of patients with AD were compared with those of
      patients with ID. PATIENTS: Consecutive patients older than 1 1/2 years diagnosed
      as having ID (n=50) and AD (n=35) were enrolled based on clinical findings.
      RESULTS: The mean ages of patients with ID and AD were 6.9 and 7.8 years,
      respectively. Histologically, both diseases were predominantly chronic dermatitis
      with propensity for skin colonization with Staphylococcus aureus and beta
      hemolytic streptococci; however, the distribution of sites of skin involvement
      differed. Infection with HTLV-I was the most distinguishing feature among
      patients with ID, with seropositive results in 100%; only 5 (14%) of the 35
      patients with AD had results seropositive for HTLV-I. Infective dermatitis was
      further characterized by dermatopathic lymphadenitis in 16 (67%) of 24 patients
      with palpable nodes. Anemia, lymphocytosis, and low albumin and elevated serum
      globulin levels were more prevalent among patients with ID. Significant
      elevations of IgA, IgD, and IgG levels were observed among patients with ID
      compared with those with AD. However, both patients with AD and those with ID had
      levels of IgD and IgE elevated above the normal range. T-cell subsets among
      patients with ID revealed T-cell activation with a high percentage of HLA-DR
      antigen positivity, elevated CD4 (2.4 x 10(9)/L) and CD8 (1.4 x 10(9)/L) cell
      counts, with an increased CD4/CD8 ratio of 1:73. CONCLUSION: Infective dermatitis
      is a distinct clinical entity associated with HTLV-I, which plays a role in the
      pathogenesis and immune perturbations observed.

PMID- 9554296
TI  - Livedo vasculopathy vs small vessel cutaneous vasculitis: cytokine and platelet P
      selectin studies.
AB  - OBJECTIVE: To assess the role of platelets and lymphocyte-related immunological
      mechanisms in livedo vasculopathy (LV) and cutaneous small vessel vasculitis
      (CSVV). Livedo vasculopathy is thought to be related to the thrombotic occlusion
      of small and medium-sized dermal vessels. Cutaneous small vessel vasculitis
      comprises a heterogeneous group of disorders in which the main pathogenetic
      events could be modulated by circulating cytokines. DESIGN: Case series study of
      2 groups of patients affected respectively with LV and CSVV. SETTING: A large
      clinical and research institute for the study and treatment of cutaneous
      diseases. PATIENTS: Consecutive patients with clinically and histologically
      proved idiopathic LV (n = 8) and CSVV (n = 20) were studied and compared with
      healthy donors (n = 20). Patients with potentially correlated systemic diseases
      were excluded. MAIN OUTCOME MEASURES: Surface expression of platelet P-selectin
      and circulating level of interleukin (IL) 1beta, tumor necrosis factor alpha (TNF
      alpha), IL-8, IL-2, and soluble IL-2 receptor. RESULTS: The IL-2 and soluble IL-2
      receptor levels were significantly higher in serum samples from patients with
      both LV (1.24 +/- 0.46 IU/mL [mean +/- SD] vs 0.46 +/- 0.24 IU/mL, P<.001; 899 +/
      368 IU/mL vs 628 +/- 132 IU/mL, P<.02) and CSVV (0.91 +/- 0.57 IU/mL, P<.02;
      1087 +/- 451 IU/mL, P<.001) than in those from the healthy controls. The serum
      levels of IL-1beta, TNF-alpha, and IL-8 were higher in patients with CSVV than in
      controls (7.53 +/- 6.7 pg/mL vs 4.58 +/- 2.72 pg/mL; 23.7 +/- 12.6 pg/mL vs 10.82
      +/- 2.46 pg/mL, P<.001; 37.8 +/- 46 pg/mL vs 8.25 +/- 3.53 pg/mL, P<.02,
      respectively). No significant difference in the serum levels of IL-1beta (7.2 +/-
      4.9 pg/mL), TNF-alpha (12.9 +/- 3.47 pg/mL), and IL-8 (5.9 +/- 4.13 pg/mL) was
      observed in patients with LV compared with controls. An increased expression of
      platelet P-selectin was also detected in patients with LV in comparison with
      controls and patients with CSVV. The mean +/- SD percentage of positive cells for
      P-selectin was 43% +/- 5% in the patients with LV, 5.1% +/- 2% in the controls
      (P<.001), and 5.3% +/- 2% in the patients with CSVV (P<.001). CONCLUSIONS: Taken
      together, these data demonstrate that different pathogenetic mechanisms are
      operative in LV and CSVV. In fact, platelet and lymphocyte activation is present
      in LV, whereas the levels of inflammatory mediators are in a normal range. In
      CSVV, the high serum levels of proinflammatory cytokines suggest that they are
      actively involved in the pathogenesis of cutaneous vasculitis.

PMID- 9554297
TI  - Acne vulgaris and the quality of life of adult dermatology patients.
AB  - OBJECTIVE: To determine the effects of acne vulgaris on the quality of life of
      adult dermatology patients. DESIGN: Cross-sectional and longitudinal
      questionnaire study. PATIENTS: Sixty patients with acne vulgaris attending
      appointments with their dermatologists. MAIN OUTCOME MEASURES: Findings using
      Skindex, a validated 29-item instrument to measure the effects of skin disease on
      patients' quality of life. Results are reported as 3 scale scores (functioning,
      emotions, and symptoms) and a composite score (average scale score). In addition,
      dermatologists rated the clinical severity of patients' skin disease, and
      patients responded to a global question about how they are bothered by acne.
      Higher Skindex scores indicate greater effects on quality of life. RESULTS:
      Patients with acne experienced functioning and emotional effects from their skin
      disease comparable with those of patients with psoriasis, but experienced fewer
      symptoms (for patients with acne and psoriasis, respectively, Skindex functioning
      scores of 14.9 and 22.8 [P=.08]; emotion scores, 39.2 and 38.9 [P=.95]; and
      symptoms scores, 29.5 and 42.1 [P<.05]). Skindex scores were higher in older
      patients than in younger patients, and patients aged 40 years or older were less
      likely to report improvement in their acne after 3 months (43% vs 85%; P<.05).
      Among patients reporting no improvement in their acne, older patients reported
      greater effects of their acne on their quality of life. Furthermore, in
      multivariate analyses, older adults reported more effects of acne on their
      quality of life than younger adults, even after controlling for sex and acne
      severity as judged by the dermatologist. CONCLUSIONS: Acne vulgaris significantly
      affects patients' quality of life. Regardless of the severity of acne, older
      adults were more affected by their acne.

PMID- 9554298
TI  - Topical cyproterone acetate treatment in women with acne: a placebo-controlled
      trial.
AB  - OBJECTIVE: To evaluate the clinical and hormonal response of topically applied
      cyproterone acetate, oral cyproterone acetate, and placebo lotion in women with
      acne. DESIGN: Placebo-controlled, randomized study. SETTING: Patients were
      recruited from the Institute of Endocrine Cosmetics, Vienna, Austria. PATIENTS:
      Forty women with acne. INTERVENTIONS: Treatment with oral medication consisting
      of 0.035 mg of ethinyl estradiol and 2 mg of cyproterone acetate (n=12), 20 mg of
      topical cyproterone acetate lotion (n=12), and placebo lotion (n=16) was offered.
      Patients were assessed monthly for 3 months. MAIN OUTCOME MEASURES: Clinical
      grading according to acne severity and lesion counts as well as determinations of
      serum cyproterone acetate concentrations. RESULTS: After 3 months of therapy with
      topical cyproterone acetate, the decrease of mean facial acne grade from 1.57 to
      0.67 was significantly better (P<.05) compared with placebo (which showed a
      change from 1.57 to 1.25), but not compared with oral medication (1.56 to 0.75)
      (P>.05). Lesion counts also decreased from 35.9 to 9.1 in the topical cyproterone
      acetate group compared with oral medication (45.4 to 15.5) (P>.05) and placebo
      (38.2 to 23.1) (P<.05). After topical cyproterone acetate treatment, serum
      cyproterone acetate concentrations were 10 times lower than those found after
      oral cyproterone acetate intake. CONCLUSIONS: The therapeutic effect of topically
      applied cyproterone acetate for acne treatment was clearly demonstrated.
      Topically applied sexual steroids in combination with liposomes are as effective
      as oral antiandrogen medication in acne treatment, while reducing the risk of
      adverse effects and avoiding high serum cyproterone acetate concentrations.

PMID- 9554299
TI  - High risk of death in elderly patients with extensive bullous pemphigoid.
AB  - OBJECTIVE: To evaluate survival and factors predicting death in bullous
      pemphigoid. DESIGN: Retrospective analysis of cohort. SETTING: Three referral
      centers (university hospitals). PATIENTS: Among 237 patients recruited between
      January 1, 1985, and December 31, 1992, 20 were excluded because of doubtful
      diagnosis. The 217 remaining patients were 79+/-11 years old (mean+/-SD); 120
      were women and 97 were men; and 79% had been treated with oral corticosteroids,
      40 to 90 mg/d. INTERVENTIONS: Missing information on follow-up was minimized by
      letters and/or telephone calls to patients, families, nursing homes, and
      physicians. MAIN OUTCOME MEASURES: Actuarial survival curve, compared with the
      expected curve as derived from census data, and evaluation of prognostic factors
      by comparing initial characteristics between patients alive at 6 months and these
      who died before that point. RESULTS: Survival curve demonstrated an early
      increased mortality: 17% at 3 months and 31% at 6 months, mainly from sepsis and
      cardiovascular diseases. Of the factors related to bullous pemphigoid activity
      (duration; pruritus; and number and extent of blisters, eosinophilia, and serum
      antibodies) only generalized pemphigoid was predictive of death in comparison
      with localized forms. In multivariate analysis, age of 86 years or more (relative
      risk, 7.1; 95% confidence interval [CI], 2.0-25.4; P < or = .01), poor general
      condition (relative risk, 8.2; 95% CI, 3.0-22.4; P < or = .001), female sex
      (relative risk, 2.4; 95% CI, 1.1-5.4; P < or = .05), and generalized disease
      (relative risk, 4.4; 95% CI, 1.4-13.7; P < or = .01) were associated with
      increased risks of death at 6 months. CONCLUSION: In this series, generalized
      bullous pemphigoid had a poor prognosis especially in older patients and those in
      poor general condition.

PMID- 9554300
TI  - Teledermatology and in-person examinations: a comparison of patient and physician
      perceptions and diagnostic agreement.
AB  - OBJECTIVE: To compare physician and patient impressions and interphysician
      diagnostic agreement between live teledermatology and in-person examinations.
      DESIGN: Paired video and in-person examinations with different dermatologists.
      SETTING: An urban Veterans Affairs dermatology clinic. PATIENTS: One hundred
      thirty-nine patients. MAIN OUTCOME MEASURES: Satisfaction questionnaires and
      interphysician diagnostic agreement. RESULTS: Patient and physician satisfaction
      was high. Agreement between video and in-person diagnoses was 80%. CONCLUSIONS:
      Physicians and patients were satisfied with teledermatology examinations.
      Diagnostic agreement between in-person and video dermatologists was high.

PMID- 9554301
TI  - Differences in Epstein-Barr virus expression between primary and secondary
      cutaneous angiocentric lymphomas. French Study Group of Cutaneous Lymphomas.
AB  - BACKGROUND: Epstein-Barr virus (EBV) has been demonstrated in angiocentric
      immunoproliferative lesions, suggesting that it could be a causative factor. We
      investigated for the presence of EBV in 12 primary and 2 secondary cutaneous
      angiocentric lymphomas (CALs). OBSERVATIONS: In the 2 secondary CALs, strong
      reactivity for EBV RNAs and latent membrane protein 1 were detected on paraffin
      embedded sections. In contrast, 10 of 12 primary CALs were completely negative
      for EBV RNAs and latent membrane protein 1. In 2 primary CALs, EBV RNAs and
      latent membrane protein 1 were detected in few tumor cells. In the group of
      primary CALs, 8 of 12 were still alive at last follow-up, 3 died of systemic
      lymphoma, and 1 died of another cause, whereas both patients with secondary CALs
      died of disease within 1 year. CONCLUSION: Differences in the presence of EBV and
      clinical behavior between primary and secondary CALs suggest that different
      mechanisms are operative in the pathogenesis of these conditions, and indicate
      that the 2 groups should be considered separately.

PMID- 9554302
TI  - Infective dermatitis: a pabulum for human T-lymphotrophic virus type I
      leukemogenesis?

PMID- 9554303
TI  - Livedoid vasculopathy: what is it?

PMID- 9554304
TI  - Persistent, solitary, erythematous, hyperkeratotic plaque.

PMID- 9554305
TI  - Woman with new-onset boggy scalp.

PMID- 9554306
TI  - An unusual papule.

PMID- 9554307
TI  - Panniculitis and ulcers in a young man.

PMID- 9554308
TI  - Interobserver variation in the assessment of rosacea.

PMID- 9554309
TI  - Are we consultants or peddlers?

PMID- 9554310
TI  - The case for sunscreens revisited.

PMID- 9554311
TI  - Helicobacter pylori in rosacea: lack of an association.

PMID- 9554312
TI  - Propolis-induced allergic contact dermatitis mimicking pemphigus vulgaris.

PMID- 9554313
TI  - Localized bullous pemphigoid following radiotherapy for breast carcinoma.

PMID- 9554314
TI  - Use of a topical fluorescent dye to evaluate effectiveness of sunscreen
      application.

PMID- 9554315
TI  - Skin involvement in male breast carcinoma.

PMID- 9554316
TI  - Basic psychopharmacology of antidepressants, part 1: Antidepressants have seven
      distinct mechanisms of action.
AB  - Distinct pharmacologic mechanisms allow the antidepressants to be separated into
      seven different classes. These basic pharmacologic concepts can explain not only
      the therapeutic actions, but also the side effects of the wide range of
      antidepressants currently available. The two classical mechanisms are those of
      tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). The
      most widely prescribed agents are the serotonin selective reuptake inhibitors
      (SSRIs). Three other classes of antidepressants, like the SSRIs, increase
      serotonergic neurotransmission, but they also have additional actions, namely
      dual serotonin and norepinephrine reuptake inhibition (venlafaxine); serotonin-2
      antagonism/reuptake inhibition (nefazodone); and alpha2 antagonism plus serotonin
      2 and -3 antagonism (mirtazapine). The selective norepinephrine and dopamine
      reuptake inhibitor bupropion defines a novel class of antidepressant that has no
      direct actions on the serotonin system.

PMID- 9554317
TI  - Basic psychopharmacology of antidepressants, part 2: Estrogen as an adjunct to
      antidepressant treatment.
AB  - Estrogen exerts profound effects upon behavior by interacting with neuronal
      estrogen receptors. Changes in estrogen levels over a woman's life cycle are
      linked not only to behavioral fluctuations, but potentially to the onset or
      recurrence of mood disorders. The modern psychiatric evaluation of women requires
      obtaining a complete reproductive history, including details of hormone
      treatments, while identifying reproductive events as triggers of affective
      disorder episodes. While guidelines for the use of reproductive hormones in
      psychiatry are just evolving, administration of estrogen as an adjunct to
      antidepressants is an exciting possibility for expanding the frontiers of
      psychiatry into the field of women's health.

PMID- 9554318
TI  - Bupropion sustained release: a therapeutic overview.
AB  - Sustained-release bupropion (bupropion SR) represents a new form of an already
      known effective antidepressant drug. Its pharmacokinetics, mechanism of action,
      metabolism, and efficacy are reviewed. Benefit relative to placebo has been
      demonstrated in two large multicenter trials, with low doses (100 or 150 mg)
      having been shown to have therapeutic efficacy. An overview of all placebo
      controlled trials of bupropion SR is given, and the differential properties of
      bupropion and serotonergic drugs are described. The concept of a catecholamine
      indolamine spectrum is presented, along with its implications for possible
      differential therapeutics of selective antidepressants.

PMID- 9554320
TI  - Drug interactions--friend or foe?
AB  - An explosion of knowledge about interactions of drugs with other drugs and with
      foods threatens to inundate clinicians. This review provides a better
      understanding of the cytochrome P450 system with a focus on those enzymes most
      involved in drug metabolism. Emphasis is placed on antidepressant medications,
      how they are metabolized by the P450 system, and how they alter the metabolism of
      other drugs. The role of antidepressants in precipitating the serotonin syndrome
      is also discussed.

PMID- 9554319
TI  - Bupropion sustained release: side effect profile.
AB  - Bupropion IR (immediate release) has been on the market since 1988 and is an
      effective and usually well-tolerated antidepressant. In late 1996, a new
      sustained-release formulation, bupropion SR, was approved and is now available.
      Compared with the IR formulation, the SR formulation demonstrates similar
      efficacy and has been found to have similar, but to some degree fewer, side
      effects. Its efficacy is similar to that of other newer antidepressants. Side
      effects of bupropion SR are limited and are not dissimilar to those of the
      serotonergic antidepressants; however, bupropion SR produces neither substantial
      sexual side effects nor drug interactions. Study data demonstrate that seizure
      incidence, which is a concern with high-dose IR, is substantially lower with the
      new SR formulation.

PMID- 9554321
TI  - Antidepressant-induced sexual dysfunction.
AB  - This article reviews current evidence regarding sexual side effects of
      antidepressant drugs. Controlled studies have demonstrated that some
      antidepressant drugs have adverse effects on orgasm and libido. Orgasmic
      dysfunction and ejaculatory delay appear to be common sexual side effects of the
      serotonin selective reuptake inhibitors (SSRIs). A variety of treatment options
      are available if a patient experiences antidepressant-induced sexual dysfunction.
      Often, modification of the pharmacologic regimen will restore sexual function
      while maintaining antidepressant activity. The frequency of sexual side effects
      reported with the SSRIs mandates that the clinician inquire about sexual function
      if these agents are used. Bupropion and nefazodone appear to have an unusually
      low incidence of sexual side effects.

PMID- 9554322
TI  - Depression, sleep, and antidepressants.
AB  - Sleep disturbances are an integral feature of depressive disorders. Like the
      disorders themselves, the sleep disturbances associated with depression are
      heterogeneous, ranging from hypersomnia to marked difficulties maintaining sleep.
      These difficulties are to some extent age dependent and reflect abnormalities of
      central nervous system arousal. Moreover, the sleep disturbances associated with
      depression have both reversible, or state-dependent, and more persistent trait
      like characteristics. Polysomnographic recordings can be used to document sleep
      maintenance difficulties, and they often also reveal reduced slow wave sleep, an
      early onset of the first episode of rapid eye movement (REM) sleep, and increased
      phasic REM sleep. A deficit of serotonergic neurotransmission, a relative
      increase in pontine cholinergic activity, and, perhaps, an excess of
      noradrenergic and corticotropin-releasing hormone activity have been implicated
      in the pathogenesis of the sleep disturbances of more severe depressive
      disorders. Antidepressant medications have class- and compound-specific effects
      on polysomnographic profiles. Unlike other antidepressants, bupropion may
      increase or intensify REM sleep. While no single effect of antidepressants on
      sleep neurophysiology is necessary or sufficient for treatment efficacy,
      differences in drug effects may provide important clues to selection of specific
      medications for particular patients.

PMID- 9554323
TI  - Bupropion sustained release and smoking cessation.
AB  - The identification of nicotine dependence as a psychiatric disorder and increased
      knowledge of nicotine's neuropharmacologic effects have stimulated researchers to
      search for new pharmacologic interventions for smoking cessation. After reviewing
      the efficacy and safety of bupropion sustained release (SR) as an agent for
      treating smoking cessation, the Food and Drug Administration recently approved
      the use of bupropion SR for this indication. This paper reviews nicotine's
      pharmacologic effects and the factors contributing to the development of nicotine
      dependence, the general principles and strategies for treating nicotine
      dependence, and the evidence for the efficacy of bupropion SR as a treatment for
      smoking cessation. The release of bupropion SR as a treatment for smoking
      cessation may provide clinicians with additional opportunities to address smoking
      cessation with their patients.

PMID- 9554324
TI  - The Expert Consensus Guidelines for treating depression in bipolar disorder.
AB  - We present expert consensus guideline recommendations for the treatment of
      bipolar depression. These were arrived at through the statistical aggregation of
      the survey responses of 61 leading clinical researchers to eight questions about
      the key decision points in the management of bipolar depression. The experts'
      first-line recommendation for treating psychotic depression in bipolar disorder
      is to provide a combination of mood stabilizer, antidepressant, and neuroleptic
      medication. For severe, but nonpsychotic bipolar depression, the experts
      recommend the combination of a mood stabilizer and an antidepressant. For milder
      bipolar depression, a mood stabilizer and an antidepressant together or a mood
      stabilizer alone would be first line. The experts' antidepressant dose and dosing
      schedule recommendations are equivalent for unipolar and bipolar depression, but
      the experts recommend a faster discontinuation of antidepressants during the
      maintenance phase in bipolar patients--probably to reduce the risk of rapid
      cycling. Among the antidepressants, the experts prefer bupropion and the
      serotonin reuptake inhibitors as first line. They also believe that bupropion is
      least likely among antidepressants to cause switches to mania. Among mood
      stabilizers, the experts rate lithium as most likely to have a direct
      antidepressant effect.

PMID- 9554325
TI  - Diagnosis and treatment of depression in late life.
AB  - Major depression and dysthymia are common and often disabling disorders in late
      life. Several features of late-life depression, such as its frequent association
      with general medical conditions, polypharmacy, cognitive disturbances, and
      adverse life events, make accurate diagnosis a substantial clinical challenge.
      Yet, prompt diagnosis is an important component of implementing appropriate
      treatment strategies. An ideal treatment program integrates patient and family
      education, focused psychotherapy, and pharmacotherapy. Because of pharmacokinetic
      and pharmacodynamic changes associated with aging, lower doses of medication and
      more gradual dose increases than are required in younger adults are needed in the
      treatment of elderly depressed patients. In addition, medications should be
      selected that have minimal antihistaminic, anticholinergic, and antiadrenergic
      effects, minimal cardiovascular risk, and minimal drug-drug interactions. Since
      depression in late life tends to be at least as chronic and/or recurrent as
      depression earlier in life, treatment for acute depressive episodes should last
      at least 6-8 months, and long-term maintenance treatment should be considered in
      selected individuals.

PMID- 9554326
TI  - ADHD through the life span: the role of bupropion in treatment.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common problem that begins
      early in life and in many cases persists through the life span. Psychostimulants
      have been the psychopharmacologic treatment of choice. Not all patients respond
      to psychostimulants, and some patients have significant side effects. This paper
      reviews the use of a nonstimulant psychopharmacologic agent, bupropion, to treat
      ADHD in both children and adults.

PMID- 9554327
TI  - Surgical trauma on the tunica albuginea.

PMID- 9554328
TI  - An analysis of watchful waiting for clinically localized prostate cancer.
AB  - PURPOSE: We reviewed recent series of watchful waiting for prostate cancer to
      place this management strategy in appropriate perspective MATERIALS AND METHODS:
      We reviewed the literature and analyzed the 9 articles on watchful waiting
      published in leading medical journals in the last decade. RESULTS: Watchful
      waiting is probably the best treatment option for men with well and perhaps
      moderately differentiated, low volume prostate cancer who have a life expectancy
      of less than 10 years. However, the conclusions derived from watchful waiting
      studies of older men cannot and should not be applied to younger, healthier men
      or to those with more advanced or aggressive disease. If treated ineffectively,
      many of these men will die of prostate cancer. CONCLUSIONS: Most men with
      prostate cancer who have a life expectancy greater than 10 to 15 years should be
      treated with curative intent.

PMID- 9554329
TI  - Locally recurrent prostate tumors following either radiation therapy or radical
      prostatectomy have changes in Ki-67 labeling index, p53 and bcl-2
      immunoreactivity.
AB  - PURPOSE: We compare the biological phenotype of recurrent prostatic tumors after
      definitive local therapy (radiation or radical prostatectomy) with that of the
      same tumors before treatment. MATERIALS AND METHODS: Cellular proliferation (Ki
      67 labeling index), p53 nuclear reactivity and bcl-2 immunoreactivity were
      determined in pretreatment and posttreatment tumor specimens from 13 patients
      with local tumor recurrence following radiation, and in 18 patients with local
      tumor recurrence following radical prostatectomy. RESULTS: Mean Ki-67 labeling
      index increased approximately 2-fold in locally recurrent tumors after radiation
      (10.5 versus 5.6%, p=0.0008) or surgery (6.0 versus 3.2%, p=0.0025) when compared
      with pretreatment tumors. We noted p53 nuclear reactivity in a significantly
      higher proportion of recurrences than in pretreatment tumors following radiation
      (54 versus 8%, p=0.032) and surgery (39 versus 5%, p=0.022). Although bcl-2
      immunoreactivity was also seen in a higher proportion of recurrent tumors, this
      difference did not reach statistical significance for either radiation or
      surgery. CONCLUSIONS: Recurrent tumors following either radiation or surgery
      differ significantly from the corresponding pretreatment tumors with respect to
      cellular proliferation and p53 nuclear reactivity.

PMID- 9554330
TI  - Differential expression of urinary inter-alpha-trypsin inhibitor trimers and
      dimers in normal compared to active calcium oxalate stone forming men.
AB  - PURPOSE: We determine if the immunoreactive profile of urinary inter-alpha
      trypsin inhibitor can be used to distinguish between normal individuals and
      individuals with calcium oxalate stone disease. MATERIALS AND METHODS: Urinary
      proteins were dialyzed against water (15 kDa. molecular weight cutoff),
      lyophilized and resolved by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (6% acrylamide, reducing conditions) followed by Western blot.
      Inter-alpha-trypsin immunoreactive proteins were detected by enhanced
      chemiluminescence. Stone formation was confirmed to be active radiologically or
      passed as stone or gravel within 12 months of the sample. Stone composition was
      confirmed crystallographically. Normal individuals had no personal or familial
      history of urolithiasis and matched stone forming patients regarding race (white)
      and age (23 to 71 years old). Urine from a total of 101 individuals was analyzed.
      RESULTS: The intact inter-alpha-trypsin trimer (approximately 220 to 240 kDa.)
      and heavy chain (HC) 2-bikunin/HC1-bikunin dimers (approximately 115 to 130 kDa.)
      were detected more often in stone forming men (23 of 26 [89%] and 26 of 26
      [100%], respectively) than in normal individuals (6 of 26 [23%] and 5 of 26
      [19%], respectively, p < 0.0001). In those normal individuals who expressed inter
      alpha-trypsin trimer and HC-bikunins the relative intensities were 5.3+/-1.4% and
      16.3+/-17.1% of the stone forming controls, respectively. The identity of high
      molecular weight-inter-alpha-trypsin immunoreactive bands was confirmed using
      antibodies against the individual subunits (HC1, HC2, HC3, bikunin). In contrast
      to men high molecular weight-inter-alpha-trypsin's were readily detected in
      normal and stone forming women with equal frequency (inter-alpha-trypsin-trimer
      p=0.1337, HC-bikunins p=0.2836): inter-alpha-trypsin-trimer 17 of 18 [94%] and 9
      of 13 [77%]; HC-bikunins 17 of 18 [94%] and 10 of 13 [85%]). Inter-alpha-trypsin
      trimer and HC-bikunins, respectively, were detected in 2 and 5 of 10 patients
      with chronic renal disease. Expression was not related to hematuria or
      proteinuria. CONCLUSIONS: Immunoreactive profiles of urinary proteins may be able
      to be developed into a useful diagnostic tool to identify active stone formation,
      although a separate panel may be required for men and women. It is possible that
      these differences may provide clues as to why the incidence of stone disease is
      higher in men than women.

PMID- 9554331
TI  - Sustained reduction in urinary calcium during long-term treatment with slow
      release neutral potassium phosphate in absorptive hypercalciuria.
AB  - PURPOSE: We tested whether UroPhos-K, a new slow release neutral form of
      potassium phosphate (155 mg. phosphate, 8 mEq. potassium per tablet) in a dose of
      4 tablets twice daily would produce a sustained hypocalciuric response and
      maintain bone mass in patients with absorptive hypercalciuria, a major cause of
      nephrolithiasis characterized by excessive intestinal calcium absorption
      accompanied in some patients by excessive bone loss. MATERIALS AND METHODS: A
      total of 25 patients with absorptive hypercalciuria were studied in a 4-year,
      prospective, open trial with UroPhos-K at yearly intervals during a 4-day
      inpatient physiological study with a constant metabolic diet containing 400 mg.
      calcium, 100 mEq. sodium and 800 mg. phosphate daily. RESULTS: Treatment with
      UroPhos-K caused a sustained, marked reduction in urinary calcium (264 to 181 mg.
      daily). Fractional 47calcium absorption decreased modestly (74.0 to 64.6%)
      commensurate with a reduction in serum 1,25-dihydroxyvitamin D (42 to 34
      pg./ml.). Intact parathyroid hormone increased within the normal range (30 to 42
      pg./ml.). Bone mineral density was stable at the lumbar spine, femoral neck and
      distal third of the radius. CONCLUSIONS: UroPhos-K may provide a long-term
      alternative for hypercalciuric patients in whom thiazide therapy fails.

PMID- 9554332
TI  - Insights into the pathophysiology and treatment of patients with calcium oxalate
      nephrolithiasis.

PMID- 9554333
TI  - Cytokine levels in cystic renal masses associated with renal cell carcinoma.
AB  - PURPOSE: We compared cytokine levels in fluid from renal cysts with and without
      renal cell carcinoma. MATERIALS AND METHODS: Fluid was aspirated from 18 renal
      cysts without (benign) and 21 with renal cell carcinoma (malignant). Serum from
      patients with renal cell carcinoma and healthy controls was collected and
      cytokines were measured by enzyme-linked immunosorbent assay. RESULTS:
      Interleukin-6 (IL-6) and basic fibroblast growth factor concentrations were
      higher in malignant than benign cysts or serum (p <0.006). Epidermal growth
      factor levels were significantly higher in malignant cysts and serum than in
      benign cysts (p <0.01). IL-6 levels in malignant cysts positively correlated with
      the erythrocyte sedimentation rate (R=0.80) and C-reactive protein (R=0.86), and
      they were higher in grade 3 than in grade 2 tumors. Basic fibroblast growth
      factor levels were significantly higher in malignant cysts associated with
      hypervascular than hypovascular tumors (p=0.029). CONCLUSIONS: Cytokine levels in
      aspirated fluid may help to identify malignant renal cysts and indicate the
      characteristics of coexisting tumors.

PMID- 9554335
TI  - Bowel dysfunction after bladder reconstruction.
AB  - PURPOSE: Bowel function may be disturbed after intestinal segments are used in
      urinary reconstruction. The etiology of this condition and its incidence in
      different patient groups is unclear. We studied the incidence of bowel
      disturbance in patients who underwent bladder replacement, continent diversion,
      enterocystoplasty for idiopathic detrusor instability and ileal conduit
      diversion. MATERIALS AND METHODS: We evaluated 71 patients after ileal conduit
      diversion and 82 after bladder reconstruction, including clam enterocystoplasty
      for detrusor instability in 28, neurogenic bladder dysfunction in 26 and
      nonneuropathic conditions in 28. We noted the severity of symptoms, such as
      frequency of defecation, nocturnal diarrhea, flatus leakage, fecal urgency, fecal
      incontinence and explosive diarrhea, as well as quality of life. RESULTS: Of the
      patients who underwent bladder reconstruction 24% had symptoms of bowel
      dysfunction preoperatively and 42% of those who were asymptomatic preoperatively
      described new bowel symptoms postoperatively. These symptoms were most common and
      severe in 54% of patients after clam enterocystoplasty for detrusor instability
      compared to 26% with neuropathy, 14% with a nonneuropathic condition and 15% with
      an ileal conduit. Compared to those in other groups patients who underwent
      enterocystoplasty for detrusor instability had a significantly higher incidence
      of nocturnal bowel movements (18 versus less than 4%, p <0.01), flatus leakage
      (29 versus less than 8%, p <0.01), fecal urgency (39 versus less than 12%, p
      <0.001) and fecal incontinence (32 versus less than 16%, p <0.001). The length of
      ileum used for clam enterocystoplasty was only slightly greater than that used
      for ileal conduit operations (25 versus 18 cm.). Of the patients who underwent
      enterocystoplasty for detrusor instability 29% regretted undergoing the procedure
      due to subsequent bowel symptoms. CONCLUSIONS: After enterocystoplasty for
      detrusor instability patients are at risk of significant bowel symptoms. The
      development of new bowel symptoms was associated with poor patient satisfaction.

PMID- 9554334
TI  - Nephron sparing surgery for renal cell carcinoma 4 cm. or less in diameter:
      indicated or under treated?
AB  - PURPOSE: Although radical nephrectomy is the standard treatment for localized
      unilateral renal cell carcinoma with a normal contralateral kidney, there is
      ongoing interest in the use of nephron sparing surgery or partial nephrectomy in
      such cases. The extent of radical surgery in such cases has also been
      reconsidered in view of the uncertainty regarding the malignant or benign nature.
      MATERIALS AND METHODS: Of 14,793 autopsies in Jena from 1985 until 1995 there
      were 260 renal cell carcinomas. Of the 260 renal cell carcinomas the diameter was
      40 mm. or less in 104. These 104 tumors were divided into group 1-20 mm. or less
      (33 cases), group 2-21 to 30 mm. (28) and group 3-31 to 40 mm. (43). RESULTS:
      Grade 1 renal cell carcinomas decreased in frequency with increasing tumor
      diameter, while an opposite result was noted for grade 3. Lymph node and distant
      metastases were well correlated with tumor size. With an increase in tumor size
      the frequency of venous involvement increased as well. Significantly more
      multifocal malignant renal cell carcinomas were seen in tumors between 21 and 40
      mm. compared to those 20 mm. or less in diameter. CONCLUSIONS: The metastatic
      potential and biology of these small nodules are not yet known. To lower the risk
      of local recurrence the results of our study suggest that nephron sparing surgery
      might be advisable in patients with renal cell carcinoma 20 mm. or less in
      diameter.

PMID- 9554336
TI  - Sacral root neuromodulation in idiopathic nonobstructive chronic urinary
      retention.
AB  - PURPOSE: Sacral root neuromodulation is becoming a superior alternative to the
      standard treatment of idiopathic nonobstructive urinary retention. We report
      results in 20 successive patients who underwent sacral foramen implantation to
      restore bladder function. MATERIALS AND METHODS: After an initial, thorough
      baseline assessment 20 patients 19.43 to 55.66 years old with idiopathic
      nonobstructive urinary retention underwent percutaneous nerve evaluation.
      Response was assessed by a detailed voiding diary. Responders underwent
      implantation with an S3 foramen implant, and were followed 1, 3 and 6 months
      postoperatively, and every 6 months thereafter. RESULTS: Sacral root
      neuromodulation restored voiding capability in these patients. Bladders were
      emptied with minimal post-void residual urine, which decreased from 78.3 to 5.5
      to 10.2% of the total voided volume from baseline to postoperative followup.
      These results were reflected in uroflowmetry and pressure-flow studies, which
      were almost normal after implantation. Furthermore, the urinary tract infection
      rate decreased significantly and associated pelvic pain improved substantially.
      The Beck depression inventory and SF-36 quality of life questionnaire indicated
      some improvement but reached significance in only 1 item. In addition,
      cystometrography showed no significant difference after 6 months of implantation
      compared with baseline values. Complications were minimal and within
      expectations. CONCLUSIONS: Sacral root neuromodulation is an appealing,
      successful modality for nonobstructive urinary retention. Only patients who have
      a good response to percutaneous nerve evaluation are candidates for implantation.
      The high efficacy in patients who undergo implantation, relative simplicity of
      the procedure and low complication rate make this a treatment breakthrough in
      this difficult group.

PMID- 9554337
TI  - The treatment of interstitial cystitis with supratrigonal cystectomy and
      ileocystoplasty: difference in outcome between classic and nonulcer disease.
AB  - PURPOSE: Interstitial cystitis is a chronic debilitating condition that mainly
      affects women. Accumulated evidence indicates that interstitial cystitis is a
      heterogeneous syndrome. The nonulcer type seems to respond less favorably to
      various conservative treatments than the classic type. Supratrigonal cystectomy
      with ileocystoplasty is established treatment for interstitial cystitis
      refractory to conservative treatment. We evaluate whether classic interstitial
      cystitis responds differently than nonulcer disease to subtotal bladder resection
      and ileocystoplasty. MATERIALS AND METHODS: We evaluated 13 patients 27 to 79
      years old with interstitial cystitis who underwent supratrigonal cystectomy and
      ileocystoplasty due to failure to respond to conservative treatment. RESULTS: In
      all 10 patients with classic interstitial cystitis symptoms were relieved after
      ileocystoplasty. In the 3 patients with nonulcer interstitial cystitis pain
      remained, while the frequency of voiding somewhat decreased. In these patients
      trigonal resection and urinary diversion with a Kock pouch resolved the symptoms.
      CONCLUSIONS: Our study confirms that supratrigonal cystectomy with
      ileocystoplasty results in a good outcome in classic interstitial cystitis.
      However, this method seems to be unsuitable for nonulcer disease. Identification
      of the relevant subtype of interstitial cystitis is of crucial importance for
      selecting the appropriate method of lower urinary tract reconstruction.

PMID- 9554338
TI  - The efficacy of intravesical bacillus Calmette-Guerin in the treatment of
      interstitial cystitis: long-term followup.
AB  - PURPOSE: Interstitial cystitis is a severe debilitating bladder disease
      characterized by unrelenting pelvic pain and urinary frequency. A prospective,
      double-blind, placebo controlled study of the use of intravesical bacillus
      Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently
      completed with a mean followup of 8 months. Results demonstrated a 60% BCG
      response rate, compared to a 27% placebo response rate. We now report the long
      term followup results of those patients who received intravesical BCG. MATERIALS
      AND METHODS: Subjects randomized to receive BCG were followed at routine
      intervals with questionnaires and voiding diaries identical to those in the
      blinded study. Adverse events were closely monitored in the treatment and
      followup phases of the study. Subject baseline values were compared to followup
      data. RESULTS: Of the BCG responders mean followup was 27 months (range 24 to
      33), and 8 of 9 (89%) continue to have an excellent response in all parameters
      measured. The global interstitial cystitis survey improved 70%, daily voids
      decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic
      pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria
      decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life
      survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia
      resolved. Of the initial BCG nonresponders there was no significant difference in
      interstitial cystitis symptomatology from baseline to last followup, suggesting
      that BCG does not worsen interstitial cystitis symptoms. No long-term adverse
      events from BCG were noted. CONCLUSIONS: Intravesical Tice BCG is safe, effective
      and durable in the treatment of interstitial cystitis. Of those patients who
      received only 6 weekly treatments and responded favorably 89% continue to have an
      excellent response with followup ranging from 24 to 33 months.

PMID- 9554339
TI  - Activation of human dendritic cells by bacillus Calmette-Guerin.
AB  - PURPOSE: Dendritic cells are the most potent antigen presenting cells capable of
      initiating antitumor immune responses. We previously showed that bacillus
      Calmette-Guerin (BCG) stimulates cultured human dendritic cells. We extended
      these studies and tested the ability of cultured human dendritic cells to express
      interleukin IL-8 in response to BCG. We also investigated the T cell stimulatory
      potential of BCG treated dendritic cells in mixed leukocyte reactions. MATERIALS
      AND METHODS: Dendritic cells were obtained by culturing plastic adherent
      mononuclear cells from peripheral blood for 6 days in the presence of granulocyte
      macrophage colony-stimulating factor and IL-4. Spontaneous and BCG stimulated IL
      8 protein release into culture supernatants was measured by a quantitative
      immunoassay. IL-8 gene transcription was assessed by reverse transcription
      polymerase chain reaction. Untreated and BCG exposed dendritic cells were
      compared as stimulators of allogeneic T cell proliferation, measured as
      [3H]thymidine incorporation. RESULTS: BCG stimulated IL-8 messenger ribonucleic
      acid expression and IL-8 protein release. IL-8 secretion occurred in a dose and
      time dependent fashion. BCG induced IL-8 release was further enhanced in the
      presence of indomethacin. BCG treated dendritic cells were much more potent T
      cell stimulators than untreated dendritic cells. CONCLUSIONS: These data
      demonstrate that BCG enhances the production of IL-8, a potent chemokine of T
      cells and granulocytes, as well as the T cell stimulatory potential of human
      dendritic cells.

PMID- 9554340
TI  - The molecular characteristics of bladder cancer in young patients.
AB  - PURPOSE: The molecular characteristics of bladder cancer in children and young
      adults remain largely undefined. We sought to identify common molecular changes
      in bladder tumors in young patients using standard immunohistochemical and
      interphase cytogenetic methods. MATERIALS AND METHODS: We retrospectively
      evaluated 73 bladder tumors removed from patients younger than 30 years for the
      p53 tumor suppressor gene product using immunohistochemical techniques and
      numerical aberrations of chromosomes 9, 17, X and Y. RESULTS: Regardless of
      stage, immunohistochemical evidence of p53 gene product over expression was found
      in the majority of tumors studied. Numerical aberrations (monosomy) of chromosome
      9 were rare. Aneuploidy of chromosome 17 was common, particularly in carcinoma in
      situ and invasive bladder cancer. CONCLUSIONS: These data suggest that
      immunohistochemical evidence of p53 gene product over expression is common in
      bladder cancer in young patients. Further prospective analysis of lesions in this
      population may help to establish a comprehensive molecular progression model for
      urothelial neoplasms.

PMID- 9554341
TI  - Carcinosarcoma and sarcomatoid carcinoma of the bladder: clinicopathological
      study of 41 cases.
AB  - PURPOSE: Carcinosarcoma of the bladder is a rare neoplasm characterized by an
      intimate admixture of carcinoma and malignant soft tissue neoplasm. The clinical
      usefulness of separating carcinosarcoma (carcinoma with sarcomatous component)
      from sarcomatoid carcinoma (carcinoma with spindle cell carcinomatous component)
      is uncertain, and it comprises the subject of this report. MATERIALS AND METHODS:
      We reviewed the clinical and pathological records of 10 men and 5 women a mean of
      66 years old with carcinosarcoma, and 21 men and 5 women a mean of 66.5 years old
      with sarcomatoid carcinoma of the bladder, as documented in the files of the Mayo
      Clinic between 1936 and 1995. RESULTS: Of the 15 patients in the carcinosarcoma
      group 9 had urothelial carcinoma, small cell carcinoma, 3 had squamous cell
      carcinoma and 2 had more than 1 type. The sarcomatous component included
      chondrosarcoma in 3 cases, leiomyosarcoma in 3, malignant fibrous histiocytoma in
      3, osteosarcoma in 2, fibrosarcoma in 1, rhabdomyosarcoma in 1 and more than 1
      type in 2. All disease was high stage at presentation. Treatment included
      cystectomy in 11 patients with (4) and without (7) radiation therapy, and
      transurethral resection in 4 with (1) and without (3) radiation therapy. Mean
      followup available in 14 cases was 34 months (range 1 to 144). A total of 11
      patients died of cancer at 1 to 48 months (mean 17.2) and 2 survived for 8 to 131
      months. Of the 26 patients in the sarcomatoid carcinoma group 18 had urothelial
      carcinoma, 1 had squamous carcinoma, 2 had urothelial carcinoma combined with
      squamous cell carcinoma and 5 had spindle cells only with no recognizable
      epithelium. All but 1 case was high stage at diagnosis. Treatment included
      transurethral resection in 17 patients with (7) and without (10) radiation
      therapy, including 1 who also received chemotherapy, and only cystectomy in 5,
      including 2 who also underwent radiation therapy and 1 who also received
      chemotherapy. Mean followup available in 21 cases was 49 months (range 1 to 420).
      A total of 17 patients died of cancer at 1 to 73 months (mean 9.8), 1 was alive
      at 140 months and 3 died of unrelated causes. CONCLUSIONS: Carcinosarcoma and
      sarcomatoid carcinoma of the bladder are highly aggressive malignancies with a
      similar outcome regardless of histological findings and treatment. Pathological
      stage is the best predictor of survival.

PMID- 9554342
TI  - Collagen injection for intrinsic sphincteric deficiency in men: a reasonable
      option in selected patients.
AB  - PURPOSE: We evaluate transurethral collagen injection as a minimally invasive
      option in treating stress urinary incontinence in men and identify the prognostic
      factors for success or failure. MATERIALS AND METHODS: Transurethral collagen was
      injected in 35 men with grades III (22) and II (13) incontinence. RESULTS: Of the
      patients 7 became dry (20%), 11 improved (31.4%) and 17 were considered failures
      (48.6%). Abdominal leak point pressure increased and the number of pads needed
      decreased. In the failed group 4 patients had a history of pelvic irradiation, 5
      urethral stricture disease and 3 bladder instability before injection. There was
      1 case of temporary urinary retention as a complication. CONCLUSIONS:
      Transurethral collagen injection for male stress urinary incontinence is a
      reasonable option in select patients.

PMID- 9554343
TI  - Delayed hypersensitivity and systemic arthralgia following transurethral collagen
      injection for stress urinary incontinence.
AB  - PURPOSE: During a prospective cohort study to determine the effectiveness of and
      adverse effects associated with transurethral collagen injection for treatment of
      stress urinary incontinence in women, we observed 3 cases of delayed allergic
      reaction at the skin test site associated with arthralgia. MATERIALS AND METHODS:
      A total of 337 women with at least a 1-year history, physical findings and
      urodynamic abnormalities consistent with stress urinary incontinence, who
      required pads or protective clothing and who had no or only grade 1 cystocele
      were enrolled in this prospective cohort study. Adverse effects were documented
      by a third party at each followup. RESULTS: Delayed reaction at the skin test
      site occurred in 3 patients (0.9%), and was associated with arthralgias in 2.
      CONCLUSIONS: The incidence and systemic nature of this type of reaction suggest
      that gluteraldehyde cross-linked collagen injection is not as innocuous as
      previously believed. Patients should be counseled regarding the unknown long-term
      outcome of this complication. Before treatment clinicians should consider double
      skin testing.

PMID- 9554344
TI  - The male bulbourethral sling procedure for post-radical prostatectomy
      incontinence.
AB  - PURPOSE: We evaluate the efficacy of the male bulbourethral sling procedure in
      the treatment of post-radical prostatectomy urinary incontinence. MATERIALS AND
      METHODS: We reviewed the records of 64 consecutive men with severe post
      prostatectomy incontinence who underwent the male bulbourethral sling procedure
      at Northwestern Memorial Hospital and Stanford University Hospital.
      Preoperatively 50% of the patients were completely incontinent (diapers, clamps
      or condom catheter), and the remainder required a mean of 4.7 pads per day. Data
      were collected by chart review, patient interviews at followup appointments and
      telephone interviews. Median followup was 18.1 months (mean 22.4, range 6.5 to
      53.8). RESULTS: Following a single sling procedure 36 patients (56%) became dry,
      and 5 (8%) were significantly improved. In 17 patients 23 retightening procedures
      were performed, which decreased the median followup to 16 months and increased
      the success rate to 75% (67% cured, 8% improved). The revision, erosion and
      infection rates were 27, 6 and 3%, respectively. CONCLUSIONS: The male
      bulbourethral sling procedure is effective treatment for post-radical
      prostatectomy urinary incontinence. Patients who had received adjuvant radiation
      therapy demonstrated a lower continence rate than those who had not. Further
      followup is needed to assess long-term efficacy.

PMID- 9554345
TI  - Sacral nerve root neuromodulation: an effective treatment for refractory urge
      incontinence.
AB  - PURPOSE: Sacral foramina implants have been recognized recently as a method for
      treatment of refractory urinary urge incontinence. We study the outcome of the
      procedure with in-depth analysis of the results of 18 implanted cases. MATERIALS
      AND METHODS: Patients with urinary urge incontinence were subjected to
      percutaneous nerve evaluation of the S3 roots as a temporary screening test to
      determine response to neuromodulation. Satisfactory responders were implanted
      with permanent sacral root neuroprosthesis. The study design included
      comprehensive voiding diaries for 4 consecutive days twice as a baseline, 1 with
      percutaneous nerve evaluation screening, 1 after the percutaneous nerve
      evaluation, 1 at the 1, 3 and 6 post-implantation visits, and every 6 months
      thereafter. Uroflowmetry and quality of life questionnaires were performed at the
      same intervals. Urodynamic study was done as a baseline and 6 months after
      implantation of the neuroprosthesis. RESULTS: All 18 patients (16 women and 2
      men) with refractory urge incontinence received a sacral foramina neuroprosthesis
      after demonstrating a good response to the percutaneous nerve evaluation. Average
      patient age at presentation was 42.3+/-3.3 years (range 22 to 67) and duration of
      urinary symptoms was 6.6+/-1.3 years (range 1.2 to 18.8). Average followup was
      18.8 months (range 3 to 83). Neuromodulation in these patients showed a marked
      reduction in leakage episodes from 6.49 to 1.98 times per 24 hours and in the
      leakage severity score. Eight patients became completely dry and 4 had average
      leakage episodes of 1 or less daily. Patients showed as well a decrease in
      urinary frequency with an increase in functional bladder capacity. Associated
      pelvic pain improved substantially. Cystometrograms demonstrated increased volume
      at first sensation by 50% and increased cystometric capacity by 15% with the
      disappearance of uninhibited contractions in 1 of the 4 patients who presented
      with it preoperatively. There was also noticeable improvement in the quality of
      life. Complication rate was low and none was life threatening. CONCLUSIONS:
      Sacral root neuromodulation is an appealing modality for treatment of urge
      incontinence refractory to conventional pharmacotherapy. The relative simplicity
      of the technique, promising results and low complication rate make this therapy a
      likely alternative.

PMID- 9554346
TI  - Management of urinary incontinence--progress and innovative strategies.

PMID- 9554347
TI  - Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin
      combinations.
AB  - PURPOSE: Transurethral alprostadil has been shown to be efficacious in many men
      with erectile dysfunction. We compared transurethral alprostadil and prazosin
      alone, and in combination to treat this disorder. MATERIALS AND METHODS: In this
      double-blind, placebo controlled study the erectile responses to transurethral
      alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234
      men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients
      self-administered a random sequence of 7 doses in the clinic in 4 weeks. The
      erectile response was assessed using categorical and visual analog scales.
      RESULTS: Full penile enlargement or rigidity was achieved by 165 of the 234 men
      (70.5%) after at least 1 active dose of medication. The most effective
      alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in
      51.8% of administrations, whereas the most effective prazosin dose (2,000
      microg.) and placebo resulted in a similar response in 12.7 and 2.7%,
      respectively (p <0.001). The 500/2,000 microg. alprostadil/prazosin combination,
      which resulted in full enlargement or rigidity in 58.9% of doses, was only
      slightly better than the most effective dose of alprostadil alone (500 microg.).
      However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were
      more effective (p <0.01) than 125 and 250 microg. alprostadil given alone,
      respectively. The most common side effect of therapy was penile pain, which
      rarely led to study discontinuation. Hypotension most commonly developed at the
      higher alprostadil-prazosin combination. CONCLUSIONS: Transurethral alprostadil
      and alprostadil-prazosin combinations produced erections in men with complete
      organic erectile dysfunction. This combination therapy may be an option in
      patients who do not respond to transurethral alprostadil alone.

PMID- 9554348
TI  - A possible mechanism for alteration of human erectile function by digoxin:
      inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase
      activity.
AB  - PURPOSE: Digoxin use has long been recognized to affect adversely male sexual
      function but the underlying mechanism is poorly understood. Digoxin is a known
      inhibitor of sodium/potassium adenosine triphosphatase (sodium pump), a plasma
      membrane enzyme that has a role in the regulation of smooth muscle tone. We
      investigated the effects of digoxin on human corpus cavernosum smooth muscle
      contractility and overall erectile function. MATERIALS AND METHODS: In human
      corporeal smooth muscle strips the in vitro effects of digoxin were assessed on
      sodium pump activity as measured by digoxin inhibitable uptake of 86rubidium,
      basal tone and endothelium dependent, neurogenic and nitric oxide donor induced
      relaxation. An in vivo prospective double-blind, placebo controlled, crossover, 4
      period investigation was performed in 6 healthy male volunteers. The effects of
      digoxin on serum hormones, erectile function questionnaire, visual sexual
      stimulation and nocturnal penile tumescence were recorded. RESULTS: In vitro
      digoxin caused concentration dependent inhibition of 86rubidium uptake (half
      maximum effect at 0.01 microM.) and contraction of corporeal smooth muscle (half
      maximum effect at 0.8 microM.). Therapeutic concentrations of digoxin (2 nM.)
      also inhibited relaxation induced by acetylcholine and electrical field
      stimulation, which release nitric oxide from corpus cavernosum endothelial cells
      and nonadrenergic noncholinergic nerves, respectively. In vivo digoxin diminished
      penile rigidity during visual sexual stimulation and nocturnal penile tumescence
      testing compared to placebo without influencing libido or serum testosterone,
      estrogen or luteinizing hormone levels. CONCLUSIONS: Digoxin associated
      alteration of human erectile function may be explained, in part, by inhibition of
      corporeal smooth muscle sodium pump activity, which promotes contraction and
      impedes nitric oxide induced relaxation. Such findings suggest therapeutic use of
      digoxin for treatment of recurrent priapism states.

PMID- 9554349
TI  - Quantifying risk of penile prosthesis infection with elevated glycosylated
      hemoglobin.
AB  - PURPOSE: Elevation of glycosylated hemoglobin above levels of 11.5 mg.% has been
      considered a contraindication to penile prosthesis implantation in diabetic
      patients. We determine the predictive value of glycosylated hemoglobin A1C in
      penile prosthesis infections in diabetic and nondiabetic patients to confirm or
      deny this prevalent opinion. MATERIALS AND METHODS: We conducted a 2-year
      prospective study of 389 patients, including 114 diabetics, who underwent 3-piece
      penile prosthesis implantation. All patients had similar preoperative preparation
      without regard to diabetic status, control or glycosylated hemoglobin A1C level.
      Risk of infection was statistically analyzed for diabetics versus nondiabetics,
      glycosylated hemoglobin A1C values above and below 11.5 mg.%, insulin dependent
      versus oral medication diabetics, and fasting blood sugars above and below 180
      mg.%. RESULTS: Prosthesis infections developed in 10 diabetics (8.7%) and 11
      nondiabetics (4.0%). No increased infection rate was observed in diabetics with
      high fasting sugars or diabetics on insulin. There was no statistically
      significant increased infection risk with increased levels of glycosylated
      hemoglobin A1C among all patients or among only the diabetics. In fact, there was
      no meaningful difference in the median or mean level of glycosylated hemoglobin
      A1C in the infected and noninfected patients regardless of diabetes. CONCLUSIONS:
      Use of glycosylated hemoglobin A1C values to identify and exclude surgical
      candidates with increased risk of infections is not proved by this study.
      Elevation of fasting sugar or insulin dependence also does not increase risk of
      infection in diabetics undergoing prosthesis implantation.

PMID- 9554350
TI  - Health outcomes variables important to patients in the treatment of erectile
      dysfunction.
AB  - PURPOSE: Erectile dysfunction is underreported and the rate of noncompliance with
      therapy is high. The National Institutes of Health Consensus Conference on
      Impotence endorsed the need for outcomes research of the various approaches to
      treatment. The purpose of our exploratory study was to begin that process through
      identification of erectile dysfunction treatment outcomes variables that are
      important to men. MATERIALS AND METHODS: The study format consisted of focus
      group meetings. The goal of the discussions was to identify variables that are
      important to men when choosing among and judging the success of treatment
      modalities for erectile dysfunction. After discussion participants were
      individually asked to identify the 10 variables that they considered important
      and rank the 5 most important variables. An importance score reflecting group
      consensus was calculated for each variable. RESULTS: Success and negative
      outcomes were identified as the 2 most important outcomes variables for all
      treatment modalities. Participants defined success in several ways. The most
      important measures of success were cure, pleasure and partner satisfaction.
      Negative outcome was defined as negative consequences associated with treatment.
      CONCLUSIONS: The focus group discussion assisted in identifying and defining
      outcomes variables important to patients with erectile dysfunction. We believe
      that understanding issues and outcomes important to such patients is necessary to
      increase compliance with treatment and, thereby, increase the success of
      treatment of this widespread condition.

PMID- 9554351
TI  - Sperm pellet analysis: a technique to detect the presence of sperm in men
      considered to have azoospermia by routine semen analysis.
AB  - PURPOSE: In men considered to have azoospermia by routine semen analyses sperm
      may be identified after centrifuging the semen. Because these sperm may be used
      for intracytoplasmic sperm injection, we describe our technique and findings of
      sperm pelleting. MATERIALS AND METHODS: Semen centrifugation for sperm pellet
      analysis was performed in 140 consecutive men in whom no sperm was identified on
      routine semen analysis and who were categorized as having obstructive or
      nonobstructive azoospermia. Obstructive azoospermia was defined as failed
      vasectomy reversal, failed reconstruction for congenital vasal or epididymal
      occlusion, or an acquired obstruction unrelated to ejaculatory duct obstruction.
      Patients with congenital absence of the vas deferens or who had undergone
      vasectomy were not included in the study. Nonobstructive azoospermia was defined
      as moderate to severe testicular atrophy with markedly elevated serum follicle
      stimulating hormone (greater than 3 times normal), or a testicular biopsy that
      revealed maturational arrest, severe hypospermatogenesis or the Sertoli-cell-only
      pattern. Obstructive and nonobstructive azoospermia were present in 70 men who
      provided 109 samples and 70 who provided 103, respectively. RESULTS: Motile and
      nonmotile sperm was identified in 13 of the 70 patients (18.6%) with obstructive
      and in 16 of the 70 (22.8%) with nonobstructive azoospermia. Pellet variability,
      that is the absence of sperm in 1 specimen and its presence in another from the
      same patient, was noted in 7 of the 17 men (41.2%) with obstructive and 2 of the
      17 (11.8%) with nonobstructive azoospermia (not statistically significant).
      Motile sperm was present in the pellets of 6 of the 70 men (8.6%) with
      obstructive and 15 of the 70 (21.4%) with nonobstructive azoospermia. The median
      number of motile sperm was lower in the obstructive than in the nonobstructive
      group (0 sperm in 17 samples versus 5 sperm in 41 samples, p <0.001). The median
      value of 0 in the obstructive azoospermia group reflects the finding that 9 of
      the 17 samples did not contain motile sperm. Similarly the median number of
      nonmotile sperm was lower in the obstructive than in the nonobstructive group (5
      versus 8 sperm). CONCLUSIONS: We demonstrated the presence of motile and
      nonmotile sperm in a significant number of men considered to have azoospermia by
      routine semen analysis. Semen centrifugation (sperm pelleting) should be
      performed in all men considered to have this condition by routine semen analysis,
      especially those with testicular failure and those in whom intracytoplasmic sperm
      injection is possible.

PMID- 9554352
TI  - Experience with vasal sperm aspiration.
AB  - PURPOSE: We describe our experience with vasal aspiration of sperm in patients
      with azoospermia secondary to neurogenic anejaculation or obstruction of the vas
      deferens. MATERIALS AND METHODS: We performed 15 vasal sperm aspirations on 11
      patients with neurogenic anejaculation or vasal obstruction. RESULTS: Adequate
      sperm was obtained from all 15 aspirations with an average sperm count of 42 x
      10[6] (range 0.5 to 252 x 10[6]) and an average motility of 73.4% (range 16 to
      100%). Aspirations were performed for use with assisted reproductive techniques
      in 12 cases and for cryopreservation alone in 3. Following assisted reproductive
      techniques 6 of the 12 aspirations (50%) resulted in pregnancy. CONCLUSIONS:
      Vasal aspiration of sperm should be considered when electroejaculation fails, is
      not available or is contraindicated. Although the overall sperm quality and
      pregnancy rate are higher with vasal aspiration and in vitro fertilization than
      electroejaculation and intrauterine insemination, vasal aspiration is a more
      technically demanding and costly approach to conception.

PMID- 9554353
TI  - Sperm acrosome status and sperm antibodies in infertility.
AB  - PURPOSE: We studied whether the spermatozoa from sperm autoimmune infertile men
      undergo premature acrosomal loss and whether this relates to the presence of
      sperm antibodies in wives. MATERIALS AND METHODS: We evaluated acrosome status of
      live washed native and overnight capacitated spermatozoa from 17 sperm
      nonautoimmune fertile and 23 sperm autoimmune infertile men using an
      immunofluorescent peanut lectin binding assay. We used cytotoxic and immunobead
      binding assays to prescreen the serum and seminal plasma of these men, and serum
      and cervical mucus of the wives for immunological infertility. We performed
      immunofluorescent sperm antibody assays on all study samples to ascertain sperm
      antibody isotype levels in each sample. Levels of acrosomal loss in husband
      native and capacitated spermatozoa were correlated with levels of IgG, IgA and
      IgM sperm antibodies in the study samples. RESULTS: Sperm autoimmune infertile
      men had a significantly larger percentage of sperm (p <0.0001) that had lost the
      acrosome and a lower percentage of sperm with intact acrosome (p <0.0001) in
      native and capacitated preparations in contrast to those of fertile controls.
      Levels of cytotoxic and IgA antibodies, especially in seminal plasma and cervical
      mucus, correlated significantly with percentages of sperm with a total loss of
      acrosome in native and capacitated sperm preparations (p < or = 0.01).
      CONCLUSION: Infertile men with sperm antibodies in serum and seminal plasma
      undergo premature acrosome loss. This loss may expose the reproductive tract
      immune system, especially that involving IgA, in autoimmune infertile men and the
      wives to high immunogenic levels of sperm acrosome membrane antigens, thereby
      rendering them immunologically infertile.

PMID- 9554354
TI  - Effects of alprostadil and prazosin on motility, viability and membrane integrity
      of human sperm.
AB  - PURPOSE: We evaluated the effects of alprostadil, prazosin hydrochloride, and
      alprostadil/prazosin hydrochloride, agents used in the clinical treatment of male
      erectile dysfunction, on the motility, viability and membrane integrity of human
      sperm. MATERIALS AND METHODS: Ten healthy volunteers provided semen samples that
      were incubated with 0.4 mg./ml. alprostadil, 0.1 and 0.2 mg./ml. prazosin
      hydrochloride and 0.4 mg./ml. alprostadil plus 0.1 mg./ml. prazosin hydrochloride
      for 2 hours. Control incubations included polyethylene glycol 1450, the
      formulation vehicle for the clinical use of alprostadil and prazosin, and Ham's F
      10 buffer. Serial evaluations of percent sperm motility, percent viability,
      membrane function (by hypo-osmotic swelling test) and several computer generated
      measurements of sperm motion, including straight line velocity, curvilinear
      velocity, linearity and amplitude of lateral head displacement, were made.
      RESULTS: None of the agents had a significant impact on the percentage of motile
      or viable sperm or on sperm membrane function. Incubation with 0.2 mg./ml.
      prazosin reduced straight line velocity and curvilinear velocity significantly
      compared with the other agents. These changes were most likely a direct result of
      the viscosity of the 0.2 mg./ml. prazosin solution and not a cellular or
      metabolic effect on the sperm. CONCLUSIONS: Alprostadil and prazosin
      hydrochloride at doses used in transurethral therapy for erectile dysfunction
      have no effect on the motility, viability and membrane integrity of human sperm.

PMID- 9554355
TI  - Breaking down the barriers to reproduction in male infertility.

PMID- 9554356
TI  - Outcomes of varicocele ligation done for pain.
AB  - PURPOSE: Surgical ligation is an option in the management of patients with
      painful varicocele. Little objective data exist addressing the effectiveness of
      this treatment. We reviewed records from 58 patients who underwent varicocele
      ligation at our institution from January 1985 to May 1996 to establish success of
      surgical ligation of the painful varicocele. MATERIALS AND METHODS: ICD-9 billing
      codes were used to identify all patients who had undergone varicocele ligation
      for pain since 1985. We documented patient age, grade and location of varicocele,
      duration and quality of pain, response to conservative therapy and surgical
      approach to ligation. Telephone interviews and chart reviews were conducted to
      determine resolution of pain, complications of the procedure and if the patient
      would choose surgery again. RESULTS: We obtained followup on 35 of the 58 painful
      varicocele patients (60%). Average patient age was 25.7 years (range 15 to 65).
      The varicocele was on the left side in 30 men and bilateral in 5. Of the patients
      31 described the pain as a dull throbbing ache, 2 as sharp and 2 as a pulling
      sensation. Initial conservative therapy failed in all 35 men. Varicocele was
      grade III in 18 cases, grade II in 16 and grade I in 1. The inguinal or
      subinguinal approach was used in 24 patients, high ligation in 10 and
      laparoscopic repair in 1. In 30 patients there was (86%) complete resolution of
      pain postoperatively and 1 had partial resolution. Only 4 patients (11%) had
      persistent or worse symptoms. CONCLUSIONS: This retrospective review supports the
      conclusion that varicocele ligation is an effective treatment for painful
      varicocele in properly selected patients.

PMID- 9554357
TI  - Transrectal ultrasound of the prostate: innovations and future applications.
AB  - PURPOSE: We present a critical evaluation of the use of ultrasound for prostate
      disease examination in urological practice, and provide perspectives on
      ultrasound applications that may become important for the future evaluation of
      prostate problems. MATERIALS AND METHODS: Based on an evaluation of clinical data
      in cases suspicious for prostatic malignancy, we addressed the apparent
      shortcomings of transrectal ultrasound for accurately diagnosing prostate cancer.
      Future applications presented in the literature were noted. RESULTS: Evaluating
      the ultrasound data in cases suspicious for malignancy indicated that imaging has
      little advantage over digital rectal examination for detecting malignant areas.
      The new applications of ultrasound that hold great promise for use in the urology
      clinic include the injection of contrast agents to obtain information on blood
      supply, temperature estimation for the noninvasive assessment of temperature
      distributions during heat treatment and a therapeutic application for local
      treatment of prostate cancer. CONCLUSIONS: While differential diagnosis with
      ultrasound appears to result in disappointing sensitivity and specificity values,
      its use in volume measurement and biopsy guidance is unquestioned. The
      development of new applications may improve the clinical value of ultrasound in
      urological practice. The application of ultrasound contrast agents for the
      detection and clinical staging of prostate cancer is especially promising. Future
      research will indicate whether the promise evolves in clinical applications.

PMID- 9554358
TI  - Association of smoking with lower urinary tract symptoms.
AB  - PURPOSE: We studied the association of smoking with lower urinary tract symptoms.
      MATERIALS AND METHODS: In 1994 we performed a population based study by mailing a
      questionnaire to all 3,143 men born in 1924, 1934 or 1944 who resided in Tampere,
      or in 11 rural or semirural municipalities in the same county. Of this population
      68% were ultimately included in the study. A modified Danish Prostate Symptom
      Score-1 was used to assess urinary symptoms and associated bothersomeness. A
      symptom index was created by multiplying the symptom and bothersomeness scores of
      hesitancy, incomplete emptying, urge, urge incontinence, nocturia and daytime
      frequency, and totaling the products. The index for lower urinary tract symptoms
      was defined as positive when it reached 7 points. Subjects were also asked
      whether they had smoked for at least a year, and they were defined as smoking
      currently, formerly and never according to the response. RESULTS: Compared with
      respondents who never smoked age adjusted odds ratios were 1.47 (95% confidence
      interval 1.09 to 1.98) and 1.38 (1.08 to 1.78), respectively, for those who
      currently and formerly smoked. After further adjusting for alcohol consumption,
      body mass index, previous prostate surgery, pelvic area surgery, prostate cancer
      and bladder cancer, the odds ratios for current and former smokers were 1.39 (95%
      confidence interval 1.02 to 1.93) and 1.34 (1.03 to 1.75), respectively.
      CONCLUSIONS: Smoking increases the prevalence of lower urinary tract symptoms.
      The similarity in the odds ratios of these symptoms between current and former
      smokers suggests that changes caused by smoking occur long term or the
      pathological process resulting in symptoms starts early in smokers. The decreased
      risk of lower urinary tract symptoms after the cessation of smoking suggests that
      the process is reversible but recovery is a long-term process.

PMID- 9554359
TI  - Intraprostatic temperature monitoring during transurethral microwave
      thermotherapy for the treatment of benign prostatic hyperplasia.
AB  - PURPOSE: We evaluated whether the results of transurethral microwave
      thermotherapy improve using high intraprostatic temperatures of 55C or greater.
      MATERIALS AND METHODS: We accrued 30 men 58 to 85 years old (mean age 69) from
      the waiting list for transurethral prostatic resection in whom maximum urinary
      flow was less than 13 ml. per second and Madsen score was greater than 8.
      According to the Abrams-Griffith nomogram all but 1 patient had obstruction.
      Before treatment 3 thin temperature probes, each containing 5 sensors in a row,
      were introduced into the prostate from the perineum and positioned using
      transurethral ultrasound guidance. The microwave power of the transurethral
      microwave thermotherapy equipment was set based on the actual temperature in the
      prostatic tissue. A temperature of at least 55C and often more than 60C was
      reached at the hottest spot. Treatment duration was 1 hour. Postoperatively an
      indwelling catheter remained in place for 2 weeks. Patients were followed for 6
      months with the first followup after 3 months. RESULTS: At the 3-month followup
      mean maximum urinary flow had increased from 7.4 to 12.5 ml. per second and the
      mean Madsen score had decreased from 12.6 to 2.9. At the 6-month followup mean
      maximum urinary flow was 12.2 ml. per second and the mean Madsen score was 3.4.
      Using pressure-flow data we divided the patients into responders and
      nonresponders. In the 18 responders maximum urinary flow had increased from 7.2
      to 14.6 ml. per second (103%), the Madsen score had decreased from 12.5 to 1.4
      (89%) and detrusor pressure had decreased from 9.2 to 6 kPa. (35%). CONCLUSIONS:
      High energy transurethral microwave thermotherapy relieved bladder outlet
      obstruction in 60% of the patients and had a good effect on symptoms. Compared
      with a previous multicenter study with 40% responders, using the same criteria
      there were 60% responders in our series. Our results indicate that better control
      of intraprostatic temperature provides better results, approaching those after
      transurethral prostatic resection.

PMID- 9554360
TI  - A prospective, randomized 1-year clinical trial comparing transurethral needle
      ablation to transurethral resection of the prostate for the treatment of
      symptomatic benign prostatic hyperplasia.
AB  - PURPOSE: We assess the 1-year efficacy and safety of transurethral needle
      ablation of the prostate compared to transurethral resection of the prostate for
      the treatment of symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND
      METHODS: A prospective, randomized clinical trial of 121 men 50 years old or
      older with symptomatic BPH was performed at 7 medical centers across the United
      States. Of the men 65 (54%) were treated with transurethral needle ablation of
      the prostate and 56 (46%) underwent transurethral resection of the prostate. Mean
      and percentage changes from baseline and between cohorts for American Urological
      Association (AUA) symptom score, AUA bother score, quality of life score, peak
      urinary flow rate and post-void residual urine volume were measured at 1, 3, 6
      and 12 months following treatment. Length of procedure, hospitalization, type of
      anesthesia, post-procedure catheterization, side effects and sexual function were
      compared. RESULTS: Transurethral needle ablation and resection resulted in a
      statistically significant improvement in AUA symptom, bother and quality of life
      scores, peak urinary flow rate and post-void residual. At 1-year followup, needle
      ablation and resection were equally effective in enhancing quality of life.
      Needle ablation had less effect on sexual function, with resection being
      associated with a greater incidence of retrograde ejaculation. Needle ablation
      could be performed as an outpatient procedure with local anesthesia while
      resection required anesthesia and hospitalization. Needle ablation was associated
      with markedly fewer side effects than resection. CONCLUSIONS: Compared to
      transurethral resection of the prostate, transurethral needle ablation of the
      prostate is an efficacious, minimally invasive treatment for symptomatic BPH that
      is associated with few side effects.

PMID- 9554361
TI  - Ratio of free-to-total prostate specific antigen in serum cannot distinguish
      patients with prostate cancer from those with chronic inflammation of the
      prostate.
AB  - PURPOSE: We demonstrate the effect of chronic inflammation of the prostate on the
      ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a
      percentage of free PSA and, therefore, that percentage of free PSA is an
      unspecific means to distinguish among prostate cancer, chronic prostatitis and
      benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Total, free and
      percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH
      and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was
      histopathologically confirmed by microscopic examination of prostatic specimens
      after sextant biopsy, transurethral prostatic resection or prostatectomy.
      RESULTS: The median values of total, free and percentage of free PSA were 4.11
      microg./l., 0.75 microg./l. and 20.4% in patients with BPH, 10.0 microg./l., 0.84
      microg./l. and 8.5% in those with prostate cancer, and 7.60 microg./l., 1.23
      microg./l. and 10.6% in those with chronic prostatitis. Patients with prostate
      cancer and chronic prostatitis had a significantly lower percentage of free PSA
      than those with BPH. Receiver operating characteristics curve analysis showed
      that percentage of free PSA as a discriminator between prostate cancer and BPH
      was not suitable for differentiating between prostate cancer and chronic
      prostatitis. CONCLUSIONS: Chronic prostatitis is not characterized by elevated
      total PSA concentrations alone but also by a decreased percentage of free PSA, a
      tendency similar to that in prostate cancer. This unspecific change in percentage
      of free PSA must be considered to interpret the percentage of free PSA correctly.

PMID- 9554362
TI  - Stability of free and total prostate specific antigen in serum from patients with
      prostate carcinoma and benign hyperplasia.
AB  - PURPOSE: Instability of prostate specific antigen (PSA) in serum might complicate
      the interpretation of the free-to-total PSA ratio. We studied the in vitro
      stability of free PSA and total PSA in serum of patients with prostate cancer or
      benign prostate hyperplasia (BPH), and of elderly men without known prostate
      disease. Furthermore, we investigated conditions to stabilize the in vitro values
      in serum. MATERIALS AND METHODS: The effects of storage at 4C on free and total
      PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29
      older than 70 years. All had total PSA less than 25 microg./l. The influence of
      total PSA levels on in vitro changes in free-to-total PSA was studied in serum of
      39 other prostate cancer patients (total PSA 1.7 to 298 microg./l.).
      Stabilization studies were performed in yet another series of samples from 54
      prostate cancer patients (total PSA 1.3 to 238 microg./l.) by adjustment of serum
      pH to 5.5 before storage. Free and total PSA was measured by a commercial
      immunofluorometric assay, as well as by in-house immunofluorometric assays.
      Statistical analyses of the results were performed by analysis of variance with
      repeated measures. RESULTS: We found no difference between the results obtained
      by the 2 assay systems. After 7 days at 4C there was a slight decrease in total
      PSA in sera of prostate cancer patients, BPH patients and men older than 70
      years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and
      14.6%, respectively). The decrease of free PSA with time was significant (p
      <0.0001) in all groups but there was no significant difference among the groups
      (p=0.16). The concomitant decrease in free-to-total PSA ratio was significant in
      all groups (p <0.0001). This change was group dependent (p=0.003), with the
      largest decrease in the prostate cancer group. Large interindividual differences
      were observed. Storage at 4C for 7 days of sera of 39 patients with localized and
      disseminated prostate cancer (total PSA 1.7 to 298 microg./l.) gave a more
      pronounced decrease in free PSA than in total PSA. Adjustment of serum pH to 5.5
      had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a
      significantly smaller change in both values (p <0.0001). CONCLUSIONS: In vitro
      instability of free PSA in serum and large interindividual differences should be
      considered when using the ratio of free-to-total PSA in evaluation of patients
      with suspected prostate cancer. Serum samples should be stored frozen if not
      analyzed immediately or acidified to pH 5.5. Interpretation of data from
      determination of free-to-total PSA ratio should be done with caution if the
      sampling and storage conditions are not known.

PMID- 9554363
TI  - Prostate rebiopsy is a poor surrogate of treatment efficacy in localized prostate
      cancer.
AB  - PURPOSE: Many investigators use prostate rebiopsy as an indicator of treatment
      efficacy and tumor response of localized prostate cancer for therapies in which
      the gland remains in situ. Because of the inherent sampling error of needle
      directed biopsies, however, some men will have a false-negative rebiopsy even if
      they have had no therapy or if the therapeutic intervention was unsuccessful in
      eradicating the malignancy. We evaluate the risk of a false-negative biopsy and
      the clinical factors that influence this risk. MATERIALS AND METHODS: A total of
      90 patients undergoing radical prostatectomy for clinically localized disease
      underwent sextant biopsy of the prostate immediately after removal of the gland.
      Data collected included prostate specific antigen (PSA), hormonal status, age and
      biopsy core status. RESULTS: Of the total study population 67.8% received
      neoadjuvant hormonal therapy. While all patients had pathologically confirmed
      adenocarcinoma within the prostatectomy specimen, 45.6% demonstrated a false
      negative rebiopsy. Within a combined predictive model, PSA and hormonal status
      demonstrated a statistically significant effect on the false-negative rebiopsy
      rate. Predictive power of this combined model was high across the spectrum of
      risk for a false-negative rebiopsy. CONCLUSIONS: This series demonstrates that
      the risk of a false-negative sextant biopsy in the presence of documented
      prostate cancer is high and is affected by several factors, including PSA and
      hormonal status. These data suggest that prostate sextant rebiopsy is an
      inaccurate method of assessing the therapeutic efficacy of treatments for
      carcinoma of the prostate in which the gland remains in situ following therapy.

PMID- 9554364
TI  - Tumor cell proliferation and survival in patients with prostate cancer followed
      expectantly.
AB  - PURPOSE: Prostate cancers have different biological potentials, and aggressive
      tumors are difficult to identify when still localized. Tumor cell proliferation
      determined by MIB-1 expression has been suggested as an important predictor for
      outcome in several human cancers including the prostate. We test the possible
      prognostic value of tumor cellular proliferation in prostate cancer patients
      treated with no intent to cure. MATERIALS AND METHODS: Formalin fixed, paraffin
      embedded tumor tissue obtained at the time of diagnosis from 221 patients
      originating from a well known complete Danish prostate cancer population was
      immunohistochemically investigated. The tumor cell proliferation rate was
      determined using the MIB-1 antibody. Tumors were clinically localized in 57% of
      the patients. RESULTS: Tumor cell proliferation rate expressed by the MIB-1 score
      significantly correlated with tumor stage (p <0.001) and malignancy grade (p
      <0.001). The MIB-1 score, divided into low and high by the median value, showed
      significant association with disease specific survival in the entire study
      population (p <0.0001), as well as in the 125 patients suffering from clinically
      localized disease (p=0.018). Multivariate analyses showed that MIB-1 was a
      significant (p=0.0003) prognostic factor in the entire population, including
      advanced disease stages. However, in the theoretically curable clinically
      localized subpopulation MIB-1 was not significant (p=0.08) contrary to
      histopathological grade (p=0.02), erythrocyte sedimentation rate (p=0.02) and T
      classification (p=0.035). CONCLUSIONS: Prostate tumor cell proliferation,
      expressed by MIB-1 immunoreactivity, demonstrated significant association with
      disease specific survival. However, MIB-1 is a close alternative to
      histopathological grade in describing the natural history of clinically localized
      prostate cancer. The additional prognostic value and the practical consequence of
      tumor cell proliferation remain to be clarified.

PMID- 9554365
TI  - Endoscopic treatment of refractory filarial chyluria: a preliminary report.
AB  - PURPOSE: We report our experiences treating 5 patients who had filarial chyluria
      using an endoscopic approach. MATERIALS AND METHODS: Two men and 3 women 47 to 83
      years old with chyluria were treated with endoscopic coagulation using guide tube
      methods. Intrarenal pelvic instillation of silver nitrate was not effective in 4
      patients and catheterization was impossible in 1. RESULTS: The responsible lesion
      was successfully coagulated in all 5 patients. Because the lesion was in the
      ruptured portion of the caliceal fornix, we thought that chyluria had arisen in
      the fragile portion of the fornix (fistulization). After endoscopic treatment
      there was no recurrence in any patient. CONCLUSIONS: Endoscopy is effective and
      minimally invasive therapy for filarial chyluria.

PMID- 9554366
TI  - Back propagation neural network in the discrimination of benign from malignant
      lower urinary tract lesions.
AB  - PURPOSE: We investigated the potential value of morphometry and artificial
      intelligence tools to discriminate between benign and malignant lower urinary
      tract lesions. MATERIALS AND METHODS: The lesions included lithiasis in 50 cases,
      inflammation in 61, benign prostatic hyperplasia in 99, carcinoma in situ in 5,
      and grade I and grades II and III transitional cell carcinoma of the bladder in
      71 and 184, respectively. Images of routine processed voided urine smears stained
      by the Giemsa technique were analyzed using a custom image analysis system,
      providing a data set of 45,452 cells. A neural net model of the back propagation
      type was used to discriminate benign from malignant cells based on the extracted
      morphometric and textural features. Data from 13,636 randomly selected cells (30%
      of the total data) were used as a training set and the data from the remaining
      31,816 cells comprised the test set. In a similar attempt to discriminate at the
      patient level data on 30% of those randomly selected were used to train a back
      propagation neural net and data on the remaining 329 were used for testing.
      RESULTS: Application of the back propagation neural net enabled the correct
      classification of 95.34% of benign and 86.71% of malignant cells with overall
      90.57% accuracy. At the patient level the back propagation neural net enabled the
      correct classification of 100% of those with benign and 94.51% of those with
      malignant disease with overall 96.96% accuracy. CONCLUSIONS: The use of neural
      nets and image morphometry may increase the speed of cytological diagnosis and
      the diagnostic accuracy of voided urine cytology.

PMID- 9554367
TI  - Genitourinary small cell carcinoma: determination of clinical and therapeutic
      factors associated with survival.
AB  - PURPOSE: We assessed the prognostic impact of genitourinary small cell carcinoma
      tumor and patient characteristics, and therapy. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 180 patients with genitourinary small
      cell carcinoma in which patient and tumor characteristics, therapy, followup
      duration and survival status had been documented. Patient age, sex, primary site,
      histological features, tumor size, stage, locoregional therapy, systemic
      chemotherapy and hormonal manipulations were analyzed for association with
      survival. RESULTS: There were 106 cases of bladder, 60 prostatic, 8 renal and 6
      ureteral small cell carcinoma. Median survival was 10.5 months overall, and 7 and
      13 months for prostatic and bladder small cell carcinoma, respectively (p <0.0001
      log rank analysis). In all cases metastatic disease at presentation (p <0.008,
      risk ratio 1.9) predicted poor survival on multivariate analysis. Radical surgery
      (p <0.0001, risk ratio 0.34) and cisplatin chemotherapy (p <0.0001, risk ratio
      0.20) were the only factors that predicted improved survival on multivariate
      analysis. For prostatic small cell carcinoma primary surgical therapy (p <0.012,
      risk ratio 0.46) was the only parameter that predicted survival on univariate
      analysis. For bladder small cell carcinoma only cisplatin chemotherapy (p
      <0.0001, risk ratio 0.15) predicted survival on multivariate analysis.
      CONCLUSIONS: Genitourinary small cell carcinoma has a poor prognosis, which is
      worse in prostatic than bladder disease. Patient and tumor characteristics were
      not determinants of survival when prostatic and bladder small cell carcinoma were
      analyzed individually. For prostatic disease only primary surgical therapy was
      associated with prolonged survival, while for bladder disease cisplatin
      chemotherapy was associated with a favorable prognosis. We recommend considering
      primary surgical therapy for prostatic and cisplatin based chemotherapy for
      bladder small cell carcinoma.

PMID- 9554368
TI  - Preoperative hyperbaric oxygen therapy for radiation induced injuries.
AB  - PURPOSE: We present our experience with preoperatively administered hyperbaric
      oxygen therapy to patients who have sustained significant therapeutic radiation
      induced soft tissue injuries and subsequently undergo planned abdominal
      intervention/surgery. MATERIALS AND METHODS: From February 1993 to May 1997, 5
      patients with a history of complications following therapeutic radiation were
      prospectively treated with hyperbaric oxygen before a planned abdominal
      operation. RESULTS: All patients had uneventful hospital courses. An additional
      procedure was eventually necessary in 2 patients but with fewer radiation related
      problems following hyperbaric oxygenation. CONCLUSIONS: Hyperbaric oxygenation
      may improve postoperative outcomes when given before planned open operations in
      patients with previous therapeutic pelvic irradiation and a history of radiation
      related complications.

PMID- 9554369
TI  - Bilateral emphysematous pyelonephritis with autosomal dominant polycystic kidney
      disease.

PMID- 9554370
TI  - Continent orthotopic ileal neobladder after kidney transplant in a female patient
      with multifocal transitional cell carcinoma.

PMID- 9554371
TI  - Filarial cystitis with ureteral obstruction.

PMID- 9554372
TI  - Miliary tuberculosis of the lung in a patient treated with bacillus Calmette
      Guerin for superficial bladder cancer.

PMID- 9554373
TI  - Primary signet ring cell adenocarcinoma of the bladder with elevated serum
      carbohydrate antigens 19-9 and 50.

PMID- 9554374
TI  - Hydroxyurea in the treatment of sickle cell associated priapism.

PMID- 9554375
TI  - Bilateral metachronous testicular seminoma associated with microlithiasis.

PMID- 9554376
TI  - Re: floating kidneys: a century of nephroptosis and nephropexy.

PMID- 9554377
TI  - Re: floating kidneys: a century of nephroptosis and nephropexy.

PMID- 9554378
TI  - Re: the role of computerized tomography in the evaluation of complications after
      laparoscopic urological surgery.

PMID- 9554379
TI  - Re: Female Stress Urinary Incontinence Clinical Guidelines Panel summary report
      on surgical management of female stress urinary incontinence.

PMID- 9554380
TI  - Re: modified Nesbit procedure for the treatment of Peyronie's disease: a
      comparative outcome analysis.

PMID- 9554381
TI  - Re: leech therapy for massive scrotal hematoma following percutaneous
      transluminal angioplasty.

PMID- 9554382
TI  - Re: p53 protein and gene alterations in pathological stage C prostate carcinoma.

PMID- 9554383
TI  - Re: reverse transcriptase polymerase chain reaction for prostate specific antigen
      in the management of prostate cancer.

PMID- 9554384
TI  - Re: recurrence patterns after radical retropubic prostatectomy: clinical
      usefulness of prostate specific antigen doubling times and log slope prostate
      specific antigen.

PMID- 9554385
TI  - Can perinatal events cause neonatal urinary ascites?

PMID- 9554386
TI  - Renal angiomyolipoma in children: diagnositc difficulty in 3 patients.
AB  - PURPOSE: Because angiomyolipoma is less common in children than in adults, its
      diagnosis can be difficult. We present 3 cases of pediatric angiomyolipoma in
      which diagnostic problems resulted due to the presenting characteristics.
      MATERIALS AND METHODS: We report on 3 children with unilateral renal
      angiomyolipoma. Computerized tomography (CT) and ultrasonography revealed 3 large
      renal masses, 20, 7 and 8 cm. in diameter, respectively. A correct diagnosis was
      not made preoperatively in any case by CT, ultrasound or fine needle biopsy.
      Wilms tumor was suspected in the first patient who received preoperative
      chemotherapy. Imaging was inconclusive in the other 2 cases. RESULTS: All
      patients underwent surgical exploration and subsequent nephrectomy due to the
      large size of the tumor. At followup 33, 23 and 13 months postoperatively all
      children were well without signs of recurrence. CONCLUSIONS: It has been reported
      that the demonstration of fat on renal ultrasound and CT can diagnose
      angiomyolipoma in 95% of the cases. Most radiologists rely solely on CT
      demonstration of lipid density in the renal mass to diagnose angiomyolipoma but
      the identification at imaging of lipid tissue may be difficult in small tumors.
      In our cases the fat content of the tumors was less than 10% despite the large
      size. This low fat content results in misdiagnosis, since fatty tissue is also
      present in other renal tumors, such as lipoma, liposarcoma, teratoma and Wilms
      tumors. We recommend conservative surgery when tumor size permits in pediatric
      patients with angiomyolipoma to avoid chemotherapy.

PMID- 9554387
TI  - Renal deterioration in myelodysplastic children: urodynamic evaluation and
      clinical correlates.
AB  - PURPOSE: We determined which factors portend a higher risk of renal deterioration
      in the myelodysplastic child, and evaluated the sensitivity and predictive value.
      MATERIALS AND METHODS: We retrospectively reviewed the medical history, imaging
      studies and urodynamics of 90 children with spinal dysraphism. Median patient age
      at initial evaluation was 3 months and average followup ranged between 2 and 25
      years (average 11). We evaluated the relation of urodynamic parameters and sex to
      upper tract changes and the resolution of these changes. RESULTS: Statistically
      significant relationships were identified between the urodynamic parameters of
      leak point pressure, compliance and detrusor-sphincter dyssynergia, and renal
      deterioration but not with resolution of deterioration. Boys and girls did not
      demonstrate a significant difference among urodynamic parameters. Female patients
      had a higher incidence of reflux and parenchymal loss. CONCLUSIONS: With
      knowledge of the inherent sensitivity, specificity and predictive value of
      urodynamic parameters, selective use of urodynamics will assist in identifying
      patients at risk of renal deterioration. Female patients with reflux are at
      greatest risk of parenchymal loss. We advocate early institution of intermittent
      catheterization in patients identified as high risk for deterioration by
      urodynamics.

PMID- 9554388
TI  - Modified Lich-Gregoir ureteral reimplantation: experience of a Canadian center.
AB  - PURPOSE: Various techniques of ureteral reimplantation have been described for
      correction of vesicoureteral reflux. We report our experience regarding the
      safety and efficacy of a modified Lich-Gregoir extravesical approach. MATERIAL
      AND METHODS: From January 1991 to January 1996 we evaluated prospectively 256
      patients who underwent a modified Lich-Gregoir procedure for correction of
      vesicoureteral reflux. A total of 385 vesicoureteral units were reimplanted,
      including 41 duplex systems. The modification to the Lich-Gregoir technique we
      used consists of ending the paraureteral myotomy with an inverted Y, which
      permits easier detrusor muscle reapproximation. RESULTS: This procedure was
      successful initially in 214 of 237 patients, as confirmed by a normal voiding
      cystourethrogram 4 to 6 months postoperatively. Of the 237 cases persistent
      vesicoureteral reflux developed in 13 patients, which resolved spontaneously in 9
      after 1 year, contralateral reflux developed in 8, which was treated
      conservatively, and ureteral obstruction developed in 2. Thus, the 1-year overall
      success rate was 96%. Urinary retention developed in 12 children with bilateral
      reimplantation (8.3%) with successful recovery in all after conservative
      management with urethral catheter drainage of 1 week or less. The duration of
      hospitalization after surgery ranged from 1 to 3 days. CONCLUSIONS: The modified
      Lich-Gregoir technique of extravesical ureteral reimplantation is successful,
      simple to perform, reproducible and associated with low morbidity. It also
      requires minimal hospital stay. These results should encourage the use of this
      technique when indicated to correct vesicoureteral reflux in children.

PMID- 9554389
TI  - Ureteral tissue expansion for bladder augmentation.
AB  - PURPOSE: Ureteral augmentation is an effective method of bladder reconstruction
      using the native urothelium of a megaureter. Clinically this procedure is
      contingent on the presence of an enlarged ureter. We have iatrogenically produced
      a segmental megaureter, while preserving renal function in a pig model. The
      urothelium of the enlarged ureter was then used for augmentation cystoplasty.
      MATERIALS AND METHODS: A tissue expander suitable for insertion into the lumen of
      the ureter was constructed. The tissue expander was passed antegrade through a
      flank incision of 8 pigs, and a separate nephrostomy tube was left in place.
      During the ensuing 1 to 4 weeks the pigs underwent daily dilation of the tissue
      expander without anesthesia. After dilation the pigs underwent ureteral
      augmentation of the bladder. The segment of expanded ureter was isolated from the
      native ureter, opened and anastomosed to the bladder. The continuity of the left
      ureter was restored by primary ureteroureterostomy. The animals underwent
      cystograms at 1 and 4 weeks and were sacrificed 4 weeks after augmentation.
      Tissue was harvested for gross and microscopic histology. RESULTS: Of the 8 pigs
      starting the protocol 5 underwent successful ureteral tissue expansion followed
      by bladder augmentation. Tissue expansion was performed from 1 to 4 weeks, and
      volumes of 150 to 1,000 cc were obtained. Two to 3 weeks of dilation was optimal
      to achieve ease of dilation, and no animal showed evidence of discomfort or
      failure to thrive. All 5 animals underwent successful ureteral augmentation with
      primary ureteroureterostomy. Tissue expansion volumes of approximately 250 cc
      were optimal for tissue management and ease of augmentation. Cystograms of all
      augmented animals showed increased bladder capacity with filling of the ureteral
      segment. Histological examination of the ureteral augmentation revealed
      preservation and regeneration of the urothelial mucosa. CONCLUSIONS: The use of a
      tissue expander in the lumen of the ureter is a novel method of generating
      urothelium for use in bladder augmentation. It may provide an alternative to
      bowel in patients who require bladder augmentation. Long-term studies are
      currently under way.

PMID- 9554390
TI  - Diagnosis and grading of detrusor instability using a computerized algorithm.
AB  - PURPOSE: Detrusor instability and hyperreflexia are characterized by involuntary
      detrusor contractions in the filling phase of the voiding cycle. The diagnosis is
      made when urodynamic evaluation reveals such contractions. To compare patients
      and evaluate treatment a method is needed to quantify the degree of instability.
      We developed an instability parameter based on the area under the curve of
      involuntary detrusor contractions on conventional filling cystometry. MATERIALS
      AND METHODS: We developed an automatic method to calculate the area under the
      curve of involuntary detrusor contractions in conventional filling cystometry.
      Logistic regression was used to construct decision rules to differentiate stable
      from unstable bladders. These rules, derived from a group of 100 children, were
      applied to a second group of 77 who were independently assessed by 3 urodynamics
      experts. RESULTS: Typically 88% of the second group were correctly classified as
      stable or unstable by the automatic procedure. In the unstable subgroup there was
      poor correlation between the calculated instability parameter and the instability
      score assigned by the experts. Most likely this difference occurred because the
      experts based their opinion mainly on the amplitude of the highest unstable
      contraction and the percentage of filling time that instability was found.
      CONCLUSIONS: The proposed method of automatically grading detrusor instability
      based on the area under detrusor contractions differs from the intuitive method
      used by experts. Since no standard is available, it cannot be concluded which
      method is better. Our proposed method is objective and it results in a single
      physical value.

PMID- 9554392
TI  - Lessons learned in 3 decades of managing the prune-belly syndrome.

PMID- 9554391
TI  - Voiding function in patients with the prune-belly syndrome after Monfort
      abdominoplasty.
AB  - PURPOSE: We reviewed our experience with patients with the prune-belly syndrome
      who had undergone Monfort abdominoplasty to assess whether our clinical
      impression of improved voiding efficiency could be demonstrated objectively.
      MATERIALS AND METHODS: From 1990 to 1993, 12 patients with the prune-belly
      syndrome underwent Monfort abdominoplasty with or without concomitant
      genitourinary reconstruction. All patients completed questionnaires on voiding
      before and after abdominoplasty, incontinence, bladder sensation, urinary flow,
      history of urinary tract infections and the ability to defecate. Urodynamic
      testing was performed in 8 patients before and after abdominoplasty. RESULTS:
      Subjective changes that occurred after abdominoplasty included resolution of or
      less double voiding in 9 patients, improved urinary continence in 7, improved
      bladder fullness sensation in 11, improved urinary flow in 10 and improved
      defecation in 5. The incidence of urinary tract infections decreased from a
      preoperative average of 5.7 per patient per year to 1.2 per patient per year
      postoperatively. Urodynamics demonstrated no significant changes in the measured
      urinary flow, capacity or maximal detrusor pressure. Compliance decreased on
      average but it remained in the compliant range. However, post-void residual
      volumes did significantly decrease from a preoperative average of 40.3% of
      bladder capacity to 13% after abdominoplasty. If the 5 patients who underwent
      concomitant urinary reconstruction were excluded, the reduction in average post
      void residuals remained approximately the same, which was 40% of bladder capacity
      preoperatively to 14.3% after abdominoplasty. These data suggest that
      abdominoplasty alone was responsible for improved micturition. CONCLUSIONS: In
      addition to the cosmetic benefits and exposure provided for genitourinary
      reconstruction Monfort abdominoplasty seems to improve voiding efficiency.

PMID- 9554393
TI  - The exstrophy-epispadias complex in the duplicated lower urinary tract.
AB  - PURPOSE: The exstrophy-epispadias complex in combination with a duplicated lower
      urinary tract is an extremely rare congenital malformation. We describe 2 cases
      of bladder exstrophy in association with a duplicated lower urinary tract.
      MATERIALS AND METHODS: We analyzed the case histories of 2 patients. The first
      case had anteroposterior duplication of the bladder communicating through an
      isthmus and a duplicate urethra. The anterior system was exstrophic and
      epispadiac. The second case had a duplicate bladder without epispadias. There was
      a communication between the anterior exstrophic and posterior normal bladders. No
      other malformations were present. RESULTS: Both patients underwent excision of
      the duplicate exstrophic bladder in conjunction with primary closure of the
      abdominal wall. Postoperative continence was normal. Histological examination
      confirmed the diagnosed bladder duplication. CONCLUSIONS: Although duplication of
      the lower urinary tract in combination with the exstrophy-epispadias complex is
      extremely rare, all children presenting with an exstrophic bladder and a normal
      urethra alone or in association with an epispadiac anterior urethra should be
      evaluated for a bladder duplication with possible isthmic communication.

PMID- 9554394
TI  - Somatic function, mental health and psychosocial functioning in 22 adolescents
      with bladder exstrophy and epispadias.
AB  - PURPOSE: We report the long-term somatic outcome, mental health and psychosocial
      adjustment in adolescents with bladder exstrophy and epispadias. MATERIALS AND
      METHODS: A total of 22 adolescents 11 to 20 years old (median age 14.5),
      including 19 with bladder exstrophy and 3 with epispadias, were assessed for
      urogenital status, stoma, renal and bowel function, anorectal physiology, mental
      health and psychosocial functioning by physical examinations, semistructured
      interviews and standardized questionnaires. The parents of 21 patients were
      interviewed and completed questionnaires. Information was also obtained on
      control groups. RESULTS: Of the 22 patients 9 (41%) had no urinary diversion and
      were urinary incontinent, 6 (27%) had persistent fecal staining and anal canal
      pressures that were lower than the controls, 10 (59%) were dissatisfied with the
      penile appearance and 11 (50%) met the criteria for psychiatric diagnoses. The
      main predictors of mental health were parental warmth and patient genital
      appraisal in the 11 to 14-year age group, and parental warmth and urinary
      continence function in the 15 to 20-year age group. Psychosocial dysfunction was
      predicted by fecal incontinence in the younger group and worries about future
      sexual relationships in the older group. CONCLUSIONS: The present multimodal
      outcome study revealed that adolescents with bladder exstrophy and epispadias had
      significant physical and mental problems. Genital malformation, and urinary and
      fecal incontinence may have a negative impact on mental health and psychosocial
      functioning. Our findings emphasize the need to include psychosocial experts on
      health care teams to reveal the amount of distress caused by these anomalies and
      to offer psychosocial support.

PMID- 9554395
TI  - A prospective randomized trial comparing 2 diuresis renography techniques for
      evaluation of suspected upper urinary tract obstruction in children.
AB  - PURPOSE: We compare the diagnostic impact of 2 diuresis renography techniques for
      evaluation of suspected upper urinary tract obstruction in children. MATERIALS
      AND METHODS: A total of 72 children were randomly assigned to 1 of 2 standardized
      diuresis renography protocols. The protocols were identical, except for the time
      of furosemide (F) injection. In the F+20 scans furosemide was given 20 minutes
      after the 99mtechnetium pentetic acid radiopharmaceutical. With the modified F-15
      scans furosemide was injected 15 minutes before renography. Hydration, bladder
      catheterization, urine output determination, radiopharmaceutical injection and
      scan acquisition were identical. Renography outcomes (obstructed, nonobstructed
      or equivocal) were analyzed for the investigated side(s) and for the
      contralateral side, which was used as a control in children with suspected
      unilateral obstruction. Chi-square test was used to compare the percentage of
      obstructed and nonobstructed scans of both protocols. Fisher's exact test was
      used to compare the nonobstructed scans and equivocal results of both protocols.
      RESULTS: Of the 96 scans performed 8 were excluded because of technical problems.
      The remaining scans included 44 F+20 and 44 F-15. Of the 88 scans 10 were used to
      evaluate possible bilateral obstruction. A total of 48 boys and 24 girls were
      evaluated. Because 2 children had a solitary kidney each, the total number of
      renal units studied for outcome was 174. The F-15 scan showed 7 times more
      obstruction than the F+20 scan on the investigated side, and this difference was
      statistically significant. No obstruction was diagnosed on the contralateral side
      with either technique when used to investigate cases of suspected unilateral
      obstruction. CONCLUSIONS: The timing of the furosemide injection (F-15 scan
      versus F+20) has a significant impact on the obstructive versus nonobstructive
      renography results when evaluating children with suspected upper urinary tract
      obstruction.

PMID- 9554396
TI  - Torsion in a triorchid testis.

PMID- 9554397
TI  - The effect of surgical trauma on rat tunica albuginea.
AB  - PURPOSE: Increased TGF-beta1 protein expression in tunica albuginea has been
      found to be associated with Peyronie's disease. The present study is designed to
      investigate whether surgical trauma induces TGF-beta up-regulation and
      histological changes in rat penis. MATERIALS AND METHODS: Thirty-two adult male
      Sprague-Dawley rats were divided into two groups. The first group (n=24)
      underwent incision and suture repair of the tunica albuginea of the penis. The
      second group (n=8) received sham surgery (incision of the penile skin and
      underlying fascia) as the control group. The trauma-induced group was divided
      into four subgroups in which the rats were euthanized at 6 hours (n=6), 1 day
      (n=6), 3 days (n=6), and 8 weeks (n=6). Two sham-operated (control) animals were
      also euthanized at each of the above time points. All tunical tissues from the
      trauma-induced and sham-operated rats were collected and examined histologically
      using Trichrome and Hart elastic fiber stain. Electron microscopy was used to
      study the ultrastructural changes of both trauma induced and control specimens.
      Western blotting technique was performed to study TGF-beta protein expression in
      both experimental and sham-operated groups. RESULTS: Tissue edema and hemorrhage
      between collagen bundles are noted in the experimental groups after 6 hours, 1
      day and 3 days. At 8 weeks the most prominent changes observed were inflammatory
      cellular infiltration and disorganization of the collagen bundles. In the control
      group the tunica albuginea retains normal wavy regular appearance in all rats.
      This histological analysis is similar to the reported description of histological
      features of the acute phase of Peyronie's disease. Electron microscopy showed
      packed collagen bundles in the trauma-induced group with normal appearing elastic
      fibers. No abnormal change was detected in the control group. Immunoblot results
      revealed remarkable TGF-beta1 protein expression in 1, 5, 3, and 0 rats of trauma
      induced subgroups after 6 hours, 1 day, 3 days, and 8 weeks respectively. No TGF
      beta1 protein expression in any rats in the control group was detected. No
      significant TGF-beta2 or TGF-beta3 protein expression was observed either in the
      trauma induced group or in the control group. CONCLUSION: Trauma can induce
      histological changes similar to the acute phase of Peyronie's disease but not the
      overt picture of the chronic phase of Peyronie's disease. It can also result in
      an early but transient up-regulation of TGF-beta1 protein expression in the rat
      penis. We conclude that surgical incisional trauma does not result in Peyronie's
      disease-like changes in the tunica.

PMID- 9554398
TI  - Urethral replacement with vascularized tunica vaginalis: defining the optimal
      form of use.
AB  - PURPOSE: Residual urethral defects after failed hypospadias surgery present
      difficulties in reconstruction. In these situations, repair using vascularized
      tissue flaps remains ideal, yet challenging. In order to offer more surgical
      alternatives in these cases, the use of vascularized tunica vaginalis flaps as
      urethral replacements has recently been established in an animal model. We
      undertook the following studies to further define the role of tunica vaginalis in
      urethral reconstruction. MATERIALS AND METHODS: A vascularized flap of tunica
      vaginalis was used to replace an experimentally created 25-30 mm. gap in the
      anterior urethra of 26 rabbits, either as an onlay or tube flap. A control group
      consisting of 7 animals underwent only a segmental anterior urethral resection
      and primary re-anastomosis. RESULTS: Satisfactory urethral healing occurred in
      all control animals that survived the procedure. All 8 animals which had tunica
      vaginalis tube flap reconstruction underwent contracture of the neourethra
      probably secondary to the presence of striated cremasteric muscle elements
      brought with the tunica during mobilization. All 16 animals available for long
      term study in the onlay flap group had excellent flap viability and 100% urethral
      patency rates. The mesothelial lining of the tunica was seen to be replaced by a
      stratified epithelial lining similar to the urothelial lining of the native
      urethra. CONCLUSION: The tunica vaginalis is a viable alternative to other
      tissues presently used for urethral replacement and can be used successfully as a
      vascularized onlay flap.

PMID- 9554399
TI  - Innervation of the striated muscle of the membranous urethra of the male dog.
AB  - PURPOSE: To identify the functional innervation of the striated muscle layer of
      the post-prostatic urethra of male dogs. MATERIALS AND METHODS: Detailed anatomic
      dissection of the pelvic and pudendal nerves was carried out. The pressure and
      contractile responses to stimulation of these nerves were recorded in vivo and in
      vitro. RESULTS: Small branches of the pelvic nerve entered the membranous urethra
      but passed through the striated muscle to the inner smooth muscle layer.
      Stimulation of the nerve with 1 msec pulses at 10 Hz produced a slow contraction
      of the urethra which was unaffected by d-tubocurarine. Pudendal nerve branches
      entered the striated layer from the caudal end. Stimulation produced a rapid,
      visible contraction that was abolished by d-tubocurarine. Field stimulation of
      isolated strips of striated muscle resulted only in rapid, d-tubocurarine
      sensitive contractions. CONCLUSIONS: The striated muscle of the membranous
      urethra is innervated exclusively by the pudendal nerve.

PMID- 9554400
TI  - In vitro functional properties of the rat bladder regenerated by the bladder
      acellular matrix graft.
AB  - PURPOSE: To assess the response of rat urinary bladder regenerated by the
      homologous bladder acellular matrix graft (BAMG) to in vitro electrical and
      pharmacologic stimuli. MATERIALS AND METHODS: In Sprague-Dawley rats, partial
      cystectomy (>50%) was performed, followed by BAMG augmentation cystoplasty. After
      4 months, organ bath studies of tissue strips in 10 were used to compare the
      contractility of the BAMG regenerates and the corresponding host detrusor smooth
      muscle. RESULTS: The BAMG regenerates exhibited contractile activity to
      electrical field stimulation and a qualitatively identical pattern of response to
      muscarinic, purinergic, alpha- and beta-adrenergic drug administration and nitric
      oxide. At 4 months after surgery, the maximum forces of contraction of the BAMG
      regenerates to carbachol stimulation amounted to close to 80% of the host bladder
      response. With electrical field stimulation, they equaled 44% and 62% of the host
      bladder response after 2.5 and 4 months, respectively. Histological and
      immunohistochemical studies confirmed the presence of receptors for
      neurotransmitters that these functional in vitro studies implied. CONCLUSIONS:
      The present study provides further evidence that augmentation cystoplasty with
      the BAMG leads to functional regeneration of the rat bladder detrusor smooth
      muscle.

PMID- 9554401
TI  - Molecular analysis of P16(Ink4)/CDKN2 and P15(INK4B)/MTS2 genes in primary human
      testicular germ cell tumors.
AB  - PURPOSE: p16 (MTS 1) and p15 (MTS 2) are negative regulators of cell cycle
      progression at the G1 cell cycle checkpoint and function as tumor suppressor
      genes (TSG). Both p15 and p16 are located on chromosome 9p21 and alterations have
      been demonstrated in a variety of human malignancies and human cancer cell lines.
      In testicular germ cell tumors (TGCT) loss of heterozygosity of 9p21 to 23 has
      been observed in 41% to 72% of informative cases. The aim of our study was to
      examine TGCT and testicular cancer cell lines for deletions and mutations of the
      p15 and p16 genes. MATERIALS AND METHODS: 24 testicular germ cell tumors, 4
      testicular cancer cell lines (TERA I, TERA II, HTE, HTH), 8 benign testicular
      tumors and 9 samples of normal testicular parenchyma were examined. Examinations
      for loss of heterozygosity (LOH) on 9p21 were performed for IFNA, D9S171, D9S126,
      D9S161, D9S1748 and PKY9 locus using Southern Blot analysis. Southern Blot
      analysis of the p16 gene to examine gross alterations was done using random
      primer labeled p16 cDNA. In addition all samples were examined for mutations of
      exons 1 to 3 of p16 and exons 1 to 2 of p15 by polymerase chain reaction (PCR)
      followed by single strand conformation polymorphism (SSCP) analysis on MDE-gels.
      All observed band shifts on SSCP were further evaluated by direct DNA sequencing
      techniques. RESULTS: No major deletions were detected for p16 and p15. 42% of all
      TGCT demonstrated LOH of the IFNA locus, 16% of the D9S161 locus and 5.5% of the
      D9S171 locus. No LOH was seen for the D9S126 locus. 5/24 TGCT (21%) and 1
      testicular cancer cell line (TERA II) demonstrated band shifts for exon 2, 8/24
      TGCT (33%) and 1 testicular cancer cell line (TERA I) showed band shifts for exon
      3; 4 TGCT had an allelic loss for exon 3 on SSCP. DNA sequencing analysis for
      exon 2 demonstrated a single base substitution (G-->A) in codon 140 resulting in
      an amino acid exchange (ala-->thre) in 4 cases and a single base deletion with
      frame shift mutation in codon 142 in 2 cases. DNA sequencing analysis for exon 3
      demonstrated a polymorphism in intron 2 in all cases. For p15 no band shifts were
      observed for exons 1 to 2 in TGCT or testicular cancer cell lines; none of benign
      testicular tumors or normal control tissues demonstrated any band shifts for p15
      or p16. DISCUSSION: We demonstrated a high frequency of mutations for exon 2 in
      specimens of primary testicular germ cell tumors, but not in benign tumors or
      normal controls. We therefore believe that p16 might be involved in the
      pathogenesis of human TGCT. The polymorphisms described for exon 3 might be
      utilized for further LOH studies. The absence of mutations in p15 gene in TGCT
      specimens suggests that p15 might not play an important role in the pathogenesis
      of testicular germ cell tumors.

PMID- 9554402
TI  - Observations on seminal vesicle dynamics in an in vivo rat model.
AB  - PURPOSE: To gain understanding of the seminal vesicle as a muscular organ,
      seminal vesicle compliance and contractile properties were quantified with an in
      vivo, microsurgical rat model. MATERIALS AND METHODS: Microsurgical dissection
      was performed on anesthetized rats to enable simultaneous organ filling and
      monitoring of intraluminal pressures. The reliability and reproducibility of post
      ganglionic hypogastric nerve-induced ipsilateral (4 rats) and bilateral (5 rats)
      seminal vesicle contractile responses were assessed during repeated nerve
      stimulation. Seminal vesicle resting compliance was assessed during a constant
      saline infusion (10 rats). Functional performance curves were obtained at fixed
      fill-volumes by measuring organ contraction after nerve stimulation (4 rats).
      RESULTS: A reproducible seminal vesicle contractile response was obtained with a
      nerve stimulation interval > 15 minutes. Bilateral seminal vesicle responses were
      observed with unilateral nerve stimulation. The resting organ compliance curve
      with saline filling exhibited a characteristic, triphasic response. Functional
      performance studies revealed that contractile performance improves as the fill
      volume increases until the distensibility limit of the organ is reached.
      CONCLUSIONS: A reliable, in vivo, rat model of seminal vesicle organ compliance
      and contractility is described. The seminal vesicle is a highly contractile,
      compliant smooth muscular organ with dynamic properties analogous to that of the
      urinary bladder. This experimental system may allow for the investigation of
      pharmacologic and other physiological influences on in vivo organ activity.

PMID- 9554403
TI  - Cell-mediated autoimmune response to testis induced by bilateral testicular
      injury can be suppressed by cyclosporin A.
AB  - PURPOSE: Since the delayed type hypersensitivity (DTH) response to testis
      antigens plays a key role in the induction and/or maintenance of experimental
      autoimmune orchitis (EAO), an animal model for human immunological male
      infertility or aspermatogenesis, we have investigated the immunosuppressive
      effect of cyclosporin A (CsA) on the DTH response to autologous testicular cells
      (TC). MATERIALS AND METHODS: A DTH response to autologous TC was induced in
      C3H/HeN mice by bilateral testicular injury (trauma). CsA was administered
      intraperitoneally for 10 consecutive days before and after injury. A DTH response
      was assessed by measuring delayed footpad reaction (DFR) to autologous TC 9 days
      after injury. RESULTS: When the mice were traumatized alone, 10 mg./kg. or more
      of CsA suppressed the DTH response to autologous TC significantly. In mice
      traumatized with 100 mg./kg. of cyclophosphamide (CY)-pretreatment, 30 mg./kg. or
      more of CsA was needed to suppress the DTH response. In mice traumatized with 200
      mg./kg. of CY-pretreatment, 50 mg./kg. of CsA was needed to suppress the
      autoimmune response. CONCLUSIONS: The DTH response to autologous TC was
      suppressed significantly by administration of CsA in a dose-dependent manner. We
      have also shown the direct suppressive effect of CsA on effector cells for DTH by
      means of local passive transfer of DTH. Administration of CsA had no augmenting
      or suppressive effect on suppressor cells for DTH. CsA might be a significant
      drug for the immunosuppression of EAO and possibly for immunological male
      infertility.

PMID- 9554404
TI  - Presence and biological activity of C-type natriuretic peptide-dependent
      guanylate cyclase-coupled receptor in the penile corpus cavernosum.
AB  - PURPOSE: To investigate the presence of C-type natriuretic peptide 1-22 (CNP)
      dependent guanylyl cyclase (GC)-coupled receptor and its biological function in
      the penile erectile smooth muscle. MATERIALS AND METHODS: Experiments have been
      done in rabbit and rat to detect cyclic GMP (cGMP) generation by the activation
      of particulate GC by natriuretic peptides (NPs) in cavernosal membrane, to
      localize precise receptor using a quantitative in vitro autoradiography of the
      snap frozen sections, to define natriuretic peptide receptor (NPR) mRNA using a
      reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to monitor
      changes of erectile smooth muscle tone by NPs in the penile tissue strips.
      RESULTS: Productions of cGMP by particulate GC in the corpus cavernosum membranes
      of rabbit and rat were stimulated by CNP, atrial natriuretic peptide 1-28 (ANP)
      and brain natriuretic peptide 1-26 (BNP) with a rank order of potency of CNP >
      BNP > ANP. HS-142-1, a selective antagonist for the GC-coupled NPR, inhibited the
      CNP-stimulated cGMP production in corpus cavernosal membrane of rabbit and rat.
      Specific 125I-(Tyr[0])-CNP bindings were localized in the corpus cavernosal
      smooth muscle of rabbit with Kd of 19.92+/-3.38 nM. and Bmax of 734.64+/-139.63
      amol./mm2. B-subtype of NPR mRNA was detected in the penile corpus cavernosum of
      rat using RT-PCR technique. CNP relaxed the smooth muscle contracted by Nomega
      nitro-L-arginine methylester (L-NAME). CONCLUSIONS: These results suggest for the
      first time that CNP modulates the erectile smooth muscle tone of penis by
      predominant activation of B-subtype of NPR with augmentation of cGMP production
      via particulate GC.

PMID- 9554405
TI  - Alterations in constituent urinary proteins in response to bladder outlet
      obstruction in rats.
AB  - PURPOSE: Benign prostatic hyperplasia, resulting in bladder outflow obstruction,
      induces well recognized clinical symptoms and morphologic bladder changes.
      Despite these phenomenon, relatively little is known with regard to the precise
      molecular events occurring in the bladder as a consequence of obstruction. In an
      effort to screen for alterations in bladder gene expression induced by
      obstruction, and/or alterations in uroepithelial integrity, this study compared
      pre- and post-obstructive constituent urinary proteins in an animal model.
      MATERIALS AND METHODS: Outlet obstruction was created using a previously
      established model system. Experimental animals were surgically obstructed for
      either 2 or 7 days, at which time the urine was aspirated and the bladders
      removed and weighed. Urinary proteins were separated using 2-D PAGE. Following
      comparison of sham versus experimental animals, microsequencing was performed on
      proteins that were down regulated. RESULTS: Duplicate experiments confirmed the
      presence of outflow obstruction. Statistically significant increases (p <0.01) in
      bladder weights were seen at 2 and 7 days in the obstructed groups as compared
      with both sham and control groups. 2-D PAGE demonstrated a down regulation of
      three urinary proteins post-obstruction. Microsequencing identified these
      proteins as prostatic steroid-binding protein C3 precursor (pI=5.5, MW=15000),
      glandular kallikrein 9 (S3) precursor (pI=6.2, MW=19000), and glandular
      kallikrein 8 (P1) precursor (pI=6.2, MW=33000). CONCLUSIONS: Bladder outflow
      obstruction alters constituent urinary protein composition in an animal model
      system. The precise etiology of these alterations remains to be defined.

PMID- 9554406
TI  - Does intratesticular testosterone administration modify the evolution of
      transitory testicular ischemia in pre-pubertal rats?
AB  - PURPOSE: Testicular torsion followed by ischemia results in variable degrees of
      infertility and until now there appears to be no effective way to recover it.
      Testosterone participation in the maintenance of male sexual organs and
      spermatogenesis led us to hypothesize that intratesticular administration could
      recover ischemic injury. MATERIALS AND METHODS: We divided 40 Wistar rats in 2
      groups, of 20 each. One group was control and the other underwent a 120-minute
      testicular ischemia by means of a vascular clamp on the left spermatic cord. Each
      group was further subdivided in 2 subgroups. The first one was observed and the
      second received intratesticular testosterone 25 mg. starting on the third day
      after injury and during the next 7 consecutive days. Half the animals were
      sacrificed 30 days after injury and the remaining ones after 60 days. Weight,
      volume, number of seminiferous tubules, histology and spermatogenesis of the same
      side and contralateral testes were examined. For statistical analysis ANOVA and
      Fisher's tests were applied. RESULTS: It was found that testosterone was capable
      of acting upon volume and weight of the left testis (p=0.0001). The animals
      receiving intratesticular testosterone showed lower testicular weight and volume
      after 30 and 60 days, respectively. This subgroup also showed a higher number of
      seminiferous tubules, modified histology and absent spermatogenesis suggesting
      testicular atrophy. CONCLUSIONS: We concluded that intratesticular injection of
      testosterone 25 mg. once a day during 7 consecutive days after transitory
      testicular ischemia causes ipsilateral testis atrophy. The animals in control
      group showed testicular histological recovery 60 days after injury. There were no
      significant histological differences in the contralateral testes.

PMID- 9554407
TI  - The inhibition of calcium oxalate monohydrate crystal growth by maleic acid
      copolymers.
AB  - The crystallization of calcium oxalate monohydrate (COM) was investigated at
      conditions of constant supersaturation both in the absence and in the presence of
      synthetic maleic acid copolymers at 37C, 0.15 M NaCl. The dependence of the rates
      of COM crystallization in the absence of inhibitors was found to be second order
      at low and first order at higher supersaturations suggesting a surface diffusion
      controlled mechanism. The presence of all copolymers tested at concentration
      levels up to 5 ppm retarded the rates of COM crystal growth up to 90%. The
      decrease of the COM crystal growth rates by the polymers depended on the nature
      of the comonomer polymerized with maleic acid and the order of inhibition was
      found to be vinyl acetate > N-vinylpyrrolidone > styrene. Taking into
      consideration kinetics data published in the literature concerning the inhibition
      of COM crystal growth, it is suggested that molecular weight also plays a role,
      with more inhibition at higher molecular weights. The morphology of the COM
      crystals grown was unaffected yet the crystals growing at lower rates in the
      presence of the copolymers were larger and their size more uniform. It is
      concluded that maleic acid copolymers are strong inhibitors of the
      crystallization of COM, the inhibitory activity being more pronounced in the case
      of the linear copolymers.

PMID- 9554408
TI  - Detection of oxidative DNA damage in human sperm and the association with
      cigarette smoking.

PMID- 9554409
TI  - Physiological consequences of testicular sperm extraction.

PMID- 9554410
TI  - Local interferon-alpha2b is not an effective treatment in early-stage Peyronie's
      disease.

PMID- 9554411
TI  - The first use of meta-analysis?

PMID- 9554412
TI  - Problems involved in including women with simple hysterectomy in epidemiologic
      studies measuring the effects of hormone replacement therapy on breast cancer
      risk.

PMID- 9554413
TI  - Incidence of invasive cancers following basal cell skin cancer.
AB  - To obtain quantitative information on the risk of invasive cancers following a
      diagnosis of basal cell carcinoma (BCC) of the skin, patients with incident BCC
      cases listed in the cancer registries of the Swiss cantons of Vaud and Neuchatel
      between 1974 and 1994 were actively followed up through December 31, 1994, for
      the occurrence of subsequent invasive neoplasms. Among 11,878 persons with
      incident BCC who were followed for a total of 76,510 person-years at risk, 1,543
      metachronous cancers were observed versus 1,397.9 expected, corresponding to a
      standardized incidence ratio (SIR) of 1.1 (95% confidence interval (CI) 1.0-1.2).
      However, after exclusion of skin cancers (mostly squamous cell carcinoma and
      melanoma), 975 second primary cancers were observed versus 1,059 expected (SIR =
      0.9, 95% CI 0.8-1.0). Significant excesses were registered for cancer of the lip
      (SIR = 2.2), for squamous cell skin cancer (SIR = 4.5) and melanoma of the skin
      (SIR = 2.5), and for non-Hodgkin's lymphoma (SIR = 1.9). The SIRs were also above
      unity, though not significantly, for cancers of the salivary glands (SIR = 2.8)
      and the small intestine (SIR = 2.1) and for soft-tissue sarcomas (SIR = 1.7). The
      SIR for lung cancer was 0.9. The SIRs for salivary gland and skin cancer were
      appreciably greater below age 70 years. For most sites, particularly for squamous
      cell cancer and melanoma of the skin, the SIRs remained elevated 5 or more years
      after BCC diagnosis. The cumulative incidence of squamous cell skin cancer was
      13% at 19 years; this stresses the importance of carefully monitoring skin
      lesions among persons previously diagnosed with BCC.

PMID- 9554414
TI  - Nested case-control study of tumors of the hemopoietic and lymphatic systems
      among workers in the meat industry.
AB  - Workers in the meat industry are exposed to viruses that cause leukemia and
      lymphoma in cattle and chickens, and also to carcinogenic chemical agents. This
      case-control study, nested in a cohort of members of a meatcutters' union in
      Baltimore, Maryland, investigated whether occupational exposures are associated
      with death from tumors of the hemopoietic and lymphatic systems. Cases of these
      tumors represent all deaths which occurred in the cohort between 1949 and 1980.
      Excess risks of tumors of the hemopoietic and lymphatic systems were observed
      throughout the meat industry, except in meatpacking plants. Slaughtering
      activities involving heavy exposure to oncogenic viruses were strongly associated
      with these tumors, especially with lymphomas. Thus, elevated risks were observed
      for butchers who killed animals (odds ratio (OR) = 5.3, 95% confidence interval
      (CI) 1.0-27.0); workers in chicken-slaughtering plants (OR = 3.3, 95% CI 0.8
      13.1); and workers in cattle/sheep/pig abattoirs (OR = 2.8, 95% CI 0.8-9.5).
      Among supermarket workers, wrapping meat (mainly a female activity) was
      associated with increased risk of tumors of the hemopoietic and lymphatic systems
      (OR = 3.8, 95% CI 1.0-14.3), with the odds of both lymphomas and tumors of the
      myeloid stem cell being elevated. On the other hand, meatcutting in supermarkets
      (almost exclusively a male activity) was associated with multiple myeloma; the
      odds ratio for men was 18.0 (95% CI 1.6-207.5), with no myeloma cases being
      recorded in women. These associations persisted after limited control for
      exposures outside the industry that have also been observed to be associated with
      excess risk, such as exposure to pesticides, working/living on pig farms, and
      exposure to X-rays. The findings provide evidence that workers in the meat
      industry may be at elevated risk of tumors of the hemopoietic and lymphatic
      systems. Further studies with larger sample sizes are needed to identify more
      conclusively which exposures play an etiologic role in the occurrence of the
      different histologic types of these tumors.

PMID- 9554415
TI  - Mortality and optimal body mass index in a sample of the US population.
AB  - In this paper, the authors model the nonmonotonic relation between body mass
      index (BMI) (weight (kg)/height2 (m2)) and mortality in 13,242 black and white
      participants in the NHANES I Epidemiologic Follow-up Study in order to estimate
      the BMI at which minimum mortality occurs. The BMI of minimum mortality was 27.1
      for black men (95% confidence interval (CI) 24.8-29.4), 26.8 for black women (95%
      CI 24.7-28.9), 24.8 for white men (95% CI 23.8-25.9), and 24.3 for white women
      (95% CI 23.3-25.4). Each confidence interval included the group average. Analyses
      conducted by smoking status and after exclusion of persons with baseline illness
      and persons who died during the first 4 years of follow-up led to virtually
      identical estimates. The authors determined the range of values over which risk
      of all-cause mortality would increase no more than 20% in comparison with the
      minimum. This interval was nine BMI units wide, and it included 70% of the
      population. These results were confirmed by parallel analyses using quantiles.
      The model used allowed the estimation of parameters in the BMI-mortality
      relation. The resulting empirical findings from each of four race/sex groups,
      which are representative of the US population, demonstrate a wide range of BMIs
      consistent with minimum mortality and do not suggest that the optimal BMI is at
      the lower end of the distribution for any subgroup.

PMID- 9554416
TI  - Sex hormones and age: a cross-sectional study of testosterone and estradiol and
      their bioavailable fractions in community-dwelling men.
AB  - The role of endogenous sex hormones in many diseases makes understanding factors
      that influence levels of these hormones increasingly important. This study
      examined age-associated variations in total and bioavailable testosterone and
      estradiol levels among community-dwelling Caucasian men in Rancho Bernardo,
      California. Plasma samples obtained from 810 men aged 24-90 years in 1984-1987
      were analyzed in 1993 using radioimmunoassay. Analyses of age-hormone
      associations, adjusting for weight, body mass index, alcohol ingestion, smoking,
      physical activity, caffeine intake, specimen storage time, and disease status,
      were undertaken. Bioavailable testosterone and bioavailable estradiol levels
      decreased significantly with age independently of covariates. Total testosterone
      and estradiol levels decreased with age only when analyses were controlled for
      confounders. The importance of the age-associated decline in endogenous sex
      hormone levels, particularly levels of bioavailable testosterone and bioavailable
      estradiol, and their relation to disease and function in men deserve further
      research.

PMID- 9554418
TI  - Short-term consistency in self-reported physical functioning among elderly women:
      the Women's Health and Aging Study.
AB  - The assessment of physical functioning and disability is integral to population
      based and clinical research carried out among elderly people. Typically,
      functional status is measured through self-reported responses to questions of the
      form "Do you have difficulty [doing a specific task]?" Knowledge of the
      reliability and validity of these self-report measures is key to the
      interpretation of many research efforts, but data on these measurement parameters
      are sparse. This paper addresses this deficiency through analyses of data from
      the Weekly Substudy of the Women's Health and Aging Study, a cohort of Baltimore
      area women aged > or =65 years with moderate to severe physical disability. Self
      reported data on 20 activities, obtained weekly over a 6-month period in 1993 or
      1994, were analyzed to investigate how time intervals between assessments and a
      subject's age and baseline level of disability influenced the consistency of self
      reports of disability at both the population level and the individual level. The
      prevalence of self-reported difficulty increased with baseline disability and, to
      a lesser extent, with age group. Consistency for all items was very high over
      short time intervals, but it decreased substantially with increasing intervals
      between responses (although associations between responses remained significant
      at 24 weeks). Consistency did not vary with age or baseline disability. Graphic
      techniques and statistical methods for use with repeated binary data are also
      illustrated.

PMID- 9554417
TI  - Epidemiology of sarcopenia among the elderly in New Mexico.
AB  - Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle
      mass, in elderly people. Sarcopenia is believed to be associated with metabolic,
      physiologic, and functional impairments and disability. Methods of estimating the
      prevalence of sarcopenia and its associated risks in elderly populations are
      lacking. Data from a population-based survey of 883 elderly Hispanic and non
      Hispanic white men and women living in New Mexico (the New Mexico Elder Health
      Survey, 1993-1995) were analyzed to develop a method for estimating the
      prevalence of sarcopenia. An anthropometric equation for predicting appendicular
      skeletal muscle mass was developed from a random subsample (n = 199) of
      participants and was extended to the total sample. Sarcopenia was defined as
      appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard
      deviations below the mean of a young reference group. Prevalences increased from
      13-24% in persons under 70 years of age to >50% in persons over 80 years of age,
      and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia
      was significantly associated with self-reported physical disability in both men
      and women, independent of ethnicity, age, morbidity, obesity, income, and health
      behaviors. This study provides some of the first estimates of the extent of the
      public health problem posed by sarcopenia.

PMID- 9554419
TI  - Epidemiology of Salmonella typhimurium O:4-12 infection in Norway: evidence of
      transmission from an avian wildlife reservoir.
AB  - In 1987, a nationwide outbreak of Salmonella typhimurium O:4-12 infection traced
      to contaminated chocolate bars occurred in Norway. In the 5 years after the
      outbreak, elevated numbers of sporadic cases caused by the epidemic strain of
      Salmonella were detected, followed by a decline in subsequent years. To
      characterize the epidemiology of this infection, the authors analyzed information
      concerning all sporadic cases reported in Norway from 1966 to 1996. Of the 153
      patients infected by the outbreak strain, 43% were less than 5 years of age, and
      only three persons had acquired the infection abroad. In contrast, 46% of the
      cases attributable to other S. typhimurium O:4-12 variants and 90% of the total
      number of Salmonella infections were related to foreign travel. A distinct
      seasonality was observed: 76% of the cases appeared between January and April. At
      the same time of year, the epidemic strain was regularly encountered as the
      etiologic agent of fatal salmonellosis among wild passerine birds, suggesting an
      epidemiologic link between the avian and human cases. The strain was rarely
      isolated from other sources. From 1990 to 1992, the authors conducted a
      prospective case-control study of sporadic indigenous infections to identify risk
      factors and obtain guidance for preventive efforts. Forty-one case-patients, each
      matched by age, sex, and geographic area with two population controls, were
      enrolled. In conditional logistic regression analysis, the following
      environmental factors were independently related to an increased risk of
      infection: drinking untreated water, having direct contact with wild birds or
      their droppings, and eating snow, sand, or soil. Cases were also more likely than
      controls to report having antecedent or concurrent medical disorders. Forty-six
      percent of the study patients were hospitalized for their salmonellosis.

PMID- 9554421
TI  - Re: "Breast cancer and lactation history in Mexican women".

PMID- 9554420
TI  - Confidence limits made easy: interval estimation using a substitution method.
AB  - The use of confidence intervals has become standard in the presentation of
      statistical results in medical journals. Calculation of confidence limits can be
      straightforward using the normal approximation with an estimate of the standard
      error, and in particular cases exact solutions can be obtained from published
      tables. However, for a number of commonly used measures in epidemiology and
      clinical research, formulae either are not available or are so complex that
      calculation is tedious. The author describes how an approach to confidence
      interval estimation which has been used in certain specific instances can be
      generalized to obtain a simple and easily understood method that has wide
      applicability. The technique is applicable as long as the measure for which a
      confidence interval is required can be expressed as a monotonic function of a
      single parameter for which the confidence limits are available. These known
      confidence limits are substituted into the expression for the measure--giving the
      required interval. This approach makes fewer distributional assumptions than the
      use of the normal approximation and can be more accurate. The author illustrates
      his technique by calculating confidence intervals for Levin's attributable risk,
      some measures in population genetics, and the "number needed to be treated" in a
      clinical trial. Hitherto the calculation of confidence intervals for these
      measures was quite problematic. The substitution method can provide a practical
      alternative to the use of complex formulae when performing interval estimation,
      and even in simpler situations it has major advantages.

PMID- 9554422
TI  - Re: "Temporal trends in diabetes mortality among American Indians and Hispanics
      in New Mexico: birth cohort and period effects".

PMID- 9554423
TI  - Proposals for funding graduate medical education: the Institute of Medicine
      report in context.
AB  - Federal support of graduate medical education (GME) has been accepted as an
      intrinsic ingredient of the Medicare program since that program's inception.
      Streams of clinical income generated by teaching hospitals, medical faculty
      practice plans, Medicaid, and other state and federal sources have also made
      important contributions to GME. Although it is difficult to ascribe legislative
      intent precisely, Medicare funding seems to have been based on a 2-fold
      assumption: that GME was socially beneficial and that there were legitimate costs
      to teaching hospitals associated with their educational missions, even though
      such costs were hard to identify specifically. The benefits and costs include the
      high quality generally ascribed to a teaching hospital environment; extra
      services and teaching costs; active, unsponsored research; a higher proportion of
      complex medical conditions and care; and technology development and introduction.
      The argument for Medicare support of GME is thus partly based on better service
      to all Medicare beneficiaries, and partly on a broader social investment in
      education and teaching hospitals, with benefits accruing to both present and
      future Medicare participants. Teaching hospitals and their young physicians in
      training are also important in providing care to underserved poor populations.

PMID- 9554425
TI  - The Institute of Medicine report on graduate medical education.

PMID- 9554424
TI  - Half a loaf: is compromise the best policy?

PMID- 9554426
TI  - Antidepressant prescribing practices of outpatient psychiatrists.
AB  - BACKGROUND: The authors examined recent changes in the number and proportion of
      patients prescribed antidepressants by psychiatrists in outpatient private
      practice and characterized antidepressant prescription patterns by patient age,
      sex, race, payment source, and clinical diagnosis. METHODS: The authors analyzed
      physician-reported data from the 1985 and 1993-1994 National Ambulatory Medical
      Care Survey, focusing on visits to physicians specializing in psychiatry.
      Logistic regressions were used to examine associations between survey year and
      antidepressant prescription, adjusting for the presence of other variables.
      RESULTS: The proportion of outpatient psychiatric visits in which an
      antidepressant was prescribed increased from 23.1% (95% confidence interval [CI],
      19.7%-26.5%) in 1985 to 48.6% (95% CI, 47.5%-49.7%) in 1993-1994. After
      controlling for several patient variables, psychiatric patients were
      approximately 2.3 (95% CI, 1.8-2.9) times more likely to receive an
      antidepressant in 1993-1994 than in 1985. In 1993-1994, selective serotonin
      reuptake inhibitors accounted for approximately half of the psychiatric visits
      with an antidepressant prescription. Increases in the rate of antidepressant
      prescription were particularly evident for children and young adults; whites; new
      patients; and patients with adjustment disorders, personality disorders,
      depression not otherwise specified or dysthymia, and some anxiety disorders.
      CONCLUSIONS: During the late 1980s and early 1990s, there was a significant
      increase in the prescription of antidepressants by office-based psychiatrists.
      This increase was greatest for patients with less severe psychiatric disorders.

PMID- 9554427
TI  - Treatment of posttraumatic stress disorder by exposure and/or cognitive
      restructuring: a controlled study.
AB  - BACKGROUND: Unanswered questions from controlled studies of posttraumatic stress
      disorder concern the value of cognitive restructuring alone without prolonged
      exposure therapy and whether its combination with prolonged exposure is
      enhancing. METHODS: In a controlled study, 87 patients with posttraumatic stress
      disorder of at least 6 months' duration were randomly assigned to have 10
      sessions of 1 of 4 treatments: prolonged exposure (imaginal and live) alone;
      cognitive restructuring alone; combined prolonged exposure and cognitive
      restructuring; or relaxation without prolonged exposure or cognitive
      restructuring. RESULTS: Integrity of audiotaped treatment sessions was
      satisfactory when rated by an assessor unaware of the treatment assignment.
      Seventy-seven patients completed treatment. The pattern of results was similar
      regardless of rater, statistical method, measure, occasion, and therapist.
      Exposure and cognitive restructuring, singly or combined, improved posttraumatic
      stress disorder markedly on a broad front. Gains continued to 6-month follow-up
      and were significantly greater than the moderate improvement from relaxation.
      CONCLUSION: Both prolonged exposure and cognitive restructuring were each
      therapeutic on their own, were not mutually enhancing when combined, and were
      each superior to relaxation.

PMID- 9554428
TI  - A functional magnetic resonance imaging study of tic suppression in Tourette
      syndrome.
AB  - BACKGROUND: The inability to inhibit unwanted behaviors and impulses produces
      functional debility in a broad range of neuropsychiatric disorders. A potentially
      important model of impulse control is volitional tic suppression in Tourette
      syndrome. METHODS: Tic suppression was studied in 22 adult subjects with Tourette
      syndrome by using functional magnetic resonance imaging. Images acquired during
      periods of voluntary tic suppression were compared with images acquired when
      subjects allowed the spontaneous expression of their tics. The magnitudes of
      signal change in the images were then correlated with measures of the severity of
      tic symptoms. CONCLUSIONS: Significant changes in signal intensity were seen in
      the basal ganglia and thalamus and in anatomically connected cortical regions
      believed to subserve attention-demanding tasks. The magnitudes of regional signal
      change in the basal ganglia and thalamus correlated inversely with the severity
      of tic symptoms. These findings suggest that the pathogenesis of tics involves an
      impaired modulation of neuronal activity in subcortical neural circuits.

PMID- 9554429
TI  - Use of pattern analysis to predict differential relapse of remitted patients with
      major depression during 1 year of treatment with fluoxetine or placebo.
AB  - BACKGROUND: Delayed and persistent ("true drug") improvement characterizes the
      response to antidepressant medication. Early or nonpersistent ("placebo") benefit
      is typical of a placebo response. The prediction was that patients with a true
      drug response would sustain their benefit best if they continued to receive the
      drug and that patients with a placebo response would have an equivalent prognosis
      whether they continued to receive the drug or were switched to placebo. METHODS:
      Patients with major depression who met the study's response criteria (a modified
      Hamilton Depression Rating Scale score < or =7 and failure to meet major
      depression criteria after each of the last 3 weeks following 12 to 14 weeks of
      treatment with fluoxetine hydrochloride, 20 mg/d) were enrolled in a 50-week
      randomized placebo substitution trial during which the return of depressive
      symptoms defined relapse. The timing and persistency of response during initial
      treatment defined true drug or placebo response patterns. RESULTS: Patients with
      a true drug response pattern relapsed significantly more frequently if they were
      switched to placebo than if they continued to receive fluoxetine (P<.001 for
      weeks 12-26, P<.005 for weeks 26-50, and P<.41 for weeks 50-62). Patients with a
      placebo response pattern had an equivalent outcome whether maintained on
      fluoxetine therapy or placebo (P< .20 for weeks 12-26, test invalid for weeks 26
      50, and P<.67 for weeks 50-62). Patients with a placebo response pattern relapsed
      more often when they continued to receive fluoxetine than patients with a true
      drug response pattern (P<.01 for weeks 12-26, P<.10 for weeks 26-50, and P<.36
      for weeks 50-62). CONCLUSIONS: These findings confirm that pattern analysis
      validly differentiates true drug from nonspecific initial responses and extend
      its use to the continuation and maintenance phases of treatment for depression.
      Investigations into the mechanisms of antidepressant activity might best be
      limited to those that can account for delayed efficacy. Fluoxetine's efficacy
      during the continuation and maintenance phases of treatment may be limited to
      patients with a true drug pattern of initial response.

PMID- 9554430
TI  - Proton magnetic resonance spectroscopic imaging of cortical gray and white matter
      in schizophrenia.
AB  - OBJECTIVE: To apply in vivo proton magnetic resonance spectroscopy imaging
      estimates of N-acetylaspartate (NAA), a neuronal marker, to clarify the relative
      contribution of neuronal and glial changes to the widespread volume deficit of
      cortical gray matter seen in patients with schizophrenia with magnetic resonance
      images. METHODS: Ten male veterans meeting criteria of the DSM-IV, for
      schizophrenia and 9 healthy age-matched men for comparison were scanned using
      spectroscopic, anatomical, and field-map sequences. Instrument and collection
      variables were standardized to allow an estimation of comparable values for NAA,
      choline, and creatine for all subjects. Metabolite values from each voxel on 3
      upper cortical slices were regressed against the gray tissue proportion of that
      voxel to derive estimates of gray and white matter NAA, creatine, and choline
      concentrations. RESULTS: The volume of cortical gray matter was reduced in
      patients with schizophrenia, but NAA signal intensity from a comparable region
      was normal. In contrast, the volume of cortical white matter was normal in
      patients with schizophrenia, but NAA signal intensity from a comparable region
      was reduced. CONCLUSIONS: The lack of reduction in gray matter NAA signal
      intensity suggests that the cortical gray matter deficit in these patients
      involved both neuronal and glial compartments rather than a neurodegenerative
      process in which there is a decrease in the neuronal relative to the glial
      compartment. Reduced white matter NAA signal intensity without a white matter
      volume deficit may reflect abnormal axonal connections.

PMID- 9554431
TI  - Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently
      detoxified alcoholics.
AB  - BACKGROUND: This study evaluated the dose-related ethanol-like subjective effects
      of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine
      hydrochloride in recently detoxified alcoholics. METHODS: Twenty male inpatients
      meeting DSM-III-R criteria for alcohol dependence and who had not consumed
      alcohol for 10 to 27 days prior to the study completed 3 test days that involved
      the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or
      saline solution under randomized double-blind conditions. Ethanol-like subjective
      effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects
      Scale; visual analog scales to measure "high" and degree of similarity to
      ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol
      drinks producing similar subjective effects; and visual analog scales measuring
      ethanol craving. RESULTS: Ketamine produced dose-related ethanol-like effects on
      each scale measuring its similarity to ethanol. Its effects were more similar to
      the sedative or descending limb effects of ethanol than to the stimulant or
      ascending limb effects. Ketamine effects also were more like ethanol than
      marijuana or cocaine. Ethanol-like effects were more prominent at the higher
      ketamine dose, a dose rated as similar to greater levels of ethanol intoxication.
      However, ketamine did not increase craving for ethanol. CONCLUSION: The
      production of ethanol-like subjective effects by ketamine supports the potential
      clinical importance of NMDA receptor antagonism among the mechanisms underlying
      the subjective effects of ethanol in humans.

PMID- 9554433
TI  - Ribozymes as therapeutic agents: are we getting closer?

PMID- 9554432
TI  - Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence
      for a hyperdopaminergic mechanism.
AB  - BACKGROUND: Stress can exacerbate a number of psychiatric disorders, many of
      which are associated with prefrontal cortical (PFC) cognitive deficits.
      Biochemical studies demonstrate that mild stress preferentially increases
      dopamine turnover in the PFC. Our study examined the effects of acute, mild
      stress exposure on higher cognitive function in monkeys and the role of
      dopaminergic mechanisms in the stress response. METHODS: The effects of loud (105
      dB) noise stress were examined on a spatial working memory task (delayed
      response) dependent on the PFC, and on a reference memory task with similar motor
      and motivational demands (visual pattern discrimination) dependent on the
      inferior temporal cortex. The role of dopamine mechanisms was tested by
      challenging the stress response with agents that decrease dopamine receptor
      stimulation. RESULTS: Exposure to noise stress significantly impaired delayed
      response performance. Stress did not impair performance on "0-second" delay
      control trials and did not alter visual pattern discrimination performance, which
      is consistent with impaired PFC cognitive function rather than nonspecific
      changes in performance. Stress-induced deficits in delayed-response performance
      were ameliorated by pretreatment with drugs that block dopamine receptors
      (haloperidol, SCH 23390) or reduce stress-induced PFC dopamine turnover in
      rodents (clonidine, naloxone hydrochloride). CONCLUSIONS: These results indicate
      that stress impairs PFC cognitive function through a hyperdopaminergic mechanism.
      Stress may take the PFC "off-line" to allow more habitual responses mediated by
      posterior cortical and subcortical structures to regulate behavior. This
      mechanism may have survival value, but may often be maladaptive in human society,
      contributing to the vulnerability of the PFC in many neuropsychiatric disorders.

PMID- 9554434
TI  - "Big Smoke" has big risks: daily cigar use causes cancer, heart disease.

PMID- 9554435
TI  - Molecular diagnostics takes one small step forward.

PMID- 9554436
TI  - Specialists help cancer survivors face unexpected challenges.

PMID- 9554437
TI  - Non-physician providers may ease oncology work force crisis.

PMID- 9554438
TI  - President heeds panel's call for increased research funding.

PMID- 9554439
TI  - Transfusion-induced immunomodulation following cancer surgery: fact or fiction?

PMID- 9554440
TI  - Inhibition of tumor growth by ribozyme-mediated suppression of aberrant epidermal
      growth factor receptor gene expression.
AB  - BACKGROUND: Amplification and rearrangement of the epidermal growth factor
      receptor (EGFR) gene is frequently associated with malignant gliomas. One type of
      EGFR mutation in primary gliomas results in overexpression of an aberrant EGFR
      messenger RNA (mRNA) that lacks sequences of exons II through VI of the human
      EGFR gene. We observed that the aberrantly spliced EGFR mRNA contains a ribozyme
      cleavable sequence (5'-AAG GUA AUU-3') created by the joining of EGFR exon I to
      exon VII. We hypothesized that an appropriately designed ribozyme RNA could
      mediate site-specific cleavage of the aberrant EGFR mRNA and reduce the growth of
      aberrant EGFR-producing tumor cells. METHODS: We synthesized aberrant EGFR mRNA
      substrates and a sequence-specific hammerhead ribozyme (abEGFR-rib) to examine
      the ribozyme's activity in vitro. We also constructed an abEGFR-rib plasmid and
      introduced it into ERM5-1 cells, which are murine NIH3T3 cells transfected to
      express an aberrant EGFR complementary DNA. We measured the growth potential of
      the cotransfected cells in culture and in nude mice. RESULTS: The synthesized
      abEGFR-rib efficiently and specifically cleaved aberrant EGFR mRNA substrates in
      vitro. Expression of the transfected abEGFR-rib suppressed expression of aberrant
      EGFR mRNA in ERM5-1 cells and reduced the growth of tumors formed by the
      cotransfected cells in nude mice. Finally, the incorporation of
      bromodeoxyuridine, a measure of mitotic activity, was also decreased in abEGFR
      rib-producing ERM5-1 cells in vivo. CONCLUSION: Ribozymes targeted to aberrant
      EGFR mRNA can inhibit the growth of tumors formed by cells that express this
      mRNA.

PMID- 9554441
TI  - Role of nitric oxide in angiogenesis and tumor progression in head and neck
      cancer.
AB  - BACKGROUND: Angiogenesis (formation of new blood vessels) is associated with
      tumor growth and metastasis in patients with solid tumors, including those of the
      head and neck. Nitric oxide (NO) production may contribute to these processes. We
      assessed the role of the NO pathway in angiogenesis and tumor progression in
      patients with head and neck cancer. METHODS: Biochemical assays were used to
      measure NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP)
      levels in specimens of tumor and normal mucosa obtained from 27 patients.
      Microvessels in tumor specimens were identified by CD-31-specific
      immunohistochemical staining. Associations between microvessel densities, levels
      of NOS, and cGMP were examined by use of two-sided statistical tests. Tumor
      specimens and human squamous carcinoma A-431 cells were grown as explants on the
      corneas of rabbits, and the effect of the NOS inhibitor N(omega)-nitro-L-arginine
      methyl ester (L-NAME) was tested. RESULTS: Levels of total NOS, inducible NOS,
      and cGMP were higher in tumor specimens than in specimens of normal mucosa (all
      P<.0001). Tumor specimens from patients with lymph node metastases presented a
      higher total NOS activity (P = .005) and were markedly more vascularized than
      tumor specimens from patients with no lymph node involvement (P = .0002).
      Microvessel density at the tumor edge was an independent predictor of metastasis
      for this series of patients (odds ratio = 1.19; 95% confidence interval = 1.07
      2.89; P = .04). A-431 cells and tumor specimens exhibiting high levels of NOS
      activity induced angiogenesis in the rabbit cornea assay; when NO production was
      blocked, tumor angiogenesis and growth were repressed. CONCLUSIONS: The NO
      pathway appears to play a key role in tumor angiogenesis and spread in patients
      with head and neck cancer.

PMID- 9554442
TI  - Retinoic acid receptor beta expression and growth inhibition of gynecologic
      cancer cells by the synthetic retinoid N-(4-hydroxyphenyl) retinamide.
AB  - BACKGROUND: The synthetic retinoid N-(4-hydroxyphenyl) retinamide (4HPR) can
      inhibit the growth of tumor cells. Preliminary results from a clinical trial
      suggest that 4HPR may reduce ovarian cancer incidence. We examined the growth
      inhibitory effects of 4HPR on gynecologic cancer cell lines in vitro and the role
      of retinoid receptors in modulating this effect. METHODS: Twelve human
      gynecologic cancer cell lines (the ovarian cell lines--A224, AD10, UCI 101, UCI
      107, SKOV3, 222, CP70, ML3B, and ML5; the cervical cell lines--HT3 and ME180; and
      the endometrial cell line--Hec 1A were tested for sensitivity to 4HPR (by
      assaying cell proliferation rates). Gel electrophoretic analysis of DNA
      fragmentation was used to measure programmed cell death (apoptosis). Specific
      retinoid receptor (retinoic acid receptor [RAR] and retinoid X receptor)
      messenger RNA (mRNA) levels were measured by northern blot hybridization. AD10
      cells were stably transfected with human RARbeta complementary DNA, and the
      effect of 4HPR on cell proliferation was examined. RESULTS: 4HPR inhibited the
      growth of all 12 cell lines, but to varying degrees; IC50 values (i.e.,
      concentrations that inhibit proliferation by 50%) ranged from 0.3 to 9 microM.
      Following 4HPR treatment, ovarian cancer cells that were sensitive to 4HPR (222,
      CP70, and UCI 101; IC50 <3 microM) contained higher levels of RARbeta transcripts
      than more resistant cells (AD10, ME180, Hec 1A, and A224; IC50 > or =3 microM)
      (2.8-fold; two-sided P = .006). Anchorage-independent growth of transfected AD10
      cells expressing high levels of RARbeta was totally abolished, even in the
      absence of 4HPR; transfectants expressing low levels of RARbeta exhibited lower
      levels of anchorage-independent growth and grew more slowly in the presence of
      4HPR than control untransfected AD10 cells. CONCLUSION: 4HPR inhibited the
      proliferation of ovarian cancer cells in vitro; RARbeta expression appeared to be
      associated with this effect.

PMID- 9554443
TI  - Multiple primary cancers in families with Li-Fraumeni syndrome.
AB  - BACKGROUND: Li-Fraumeni syndrome is a dominantly inherited disorder characterized
      by early-onset breast cancer, sarcomas, and other cancers in children and young
      adults. Members of families with this syndrome also develop multiple primary
      cancers, but the frequency is unknown. To approach this issue, we quantified the
      incidence of second and third primary cancers in individuals from 24 Li-Fraumeni
      kindreds originally diagnosed with cancer during the period from 1968 through
      1986. METHODS: The relative risk (RR) of subsequent cancers and 95% confidence
      intervals (CIs) were calculated by use of population-based incidence data from
      the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the
      cumulative probability (+/- standard error) of subsequent cancers. RESULTS: Among
      200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed
      a second cancer. Eight individuals (4%) had a third cancer, while four (2%)
      eventually developed a fourth cancer. Overall, the RR of occurrence of a second
      cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer
      occurrence of 57% (+/- 10%) at 30 years after diagnosis of a first cancer. RRs of
      second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9
      187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with
      a first cancer at ages 0-19 years, 20-44 years, and 45 years or more,
      respectively. Thirty (71%) of 42 subsequent cancers in this group were component
      cancers of Li-Fraumeni syndrome. CONCLUSIONS: Compared with the general
      population, members of Li-Fraumeni syndrome families have an exceptionally high
      risk of developing multiple primary cancers. The excess risk of additional
      primary cancers is mainly for cancers that are characteristic of Li-Fraumeni
      syndrome, with the highest risk observed for survivors of childhood cancers.
      Cancer survivors in these families should be closely monitored for early
      manifestations of new cancers.

PMID- 9554444
TI  - Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo
      controlled trial for treatment of breakthrough pain in cancer patients.
AB  - BACKGROUND: Patients with cancer frequently experience episodes of acute pain,
      i.e., breakthrough pain, superimposed on their chronic pain. Breakthrough pain is
      usually treated with short-acting oral opioids, most of which provide some relief
      after 15-20 minutes, with peak effects after 30-45 minutes. Oral transmucosal
      fentanyl citrate (OTFC), a unique formulation of the opioid fentanyl, has been
      shown to provide meaningful pain relief within 5 minutes in patients following
      surgery. We conducted a multicenter, randomized, double-blinded, placebo
      controlled trial of OTFC for cancer-related breakthrough pain. METHODS: Patients
      who were 18 years of age or older, receiving the equivalent of at least 60 mg
      oral morphine or at least 50 microg transdermal fentanyl per day for chronic
      cancer-related pain, and experiencing at least one episode of breakthrough pain
      per day were studied. After titration to an effective OTFC dose, subjects were
      given 10 randomly ordered treatment units (seven OTFC units and three placebo
      units) in the form of identical lozenges. If acceptable pain relief was not
      achieved within 30 minutes, subjects were instructed to take their previous
      breakthrough pain medication (i.e., rescue medication). Pain intensity, pain
      relief, and use of rescue medication were evaluated at 15-minute intervals over a
      60-minute period. RESULTS: Eighty-nine of 92 patients who received the randomized
      treatment were assessable (i.e., treated with at least one unit of OTFC and one
      unit of placebo). OTFC produced significantly larger changes in pain intensity
      and better pain relief than placebo at all time points (two-sided P<.0001).
      Episodes treated with placebo required the use of rescue medication more often
      than episodes treated with OTFC (34% versus 15%; relative risk = 2.27; 95%
      confidence interval = 1.51-3.26; two-sided P<.0001). CONCLUSIONS: OTFC appears
      effective in the treatment of cancer-related breakthrough pain.

PMID- 9554445
TI  - Human leukocyte antigen class II alleles associated with human T-cell
      lymphotropic virus type I infection and adult T-cell leukemia/lymphoma in a Black
      population.
AB  - BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T
      cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as
      tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder.
      Worldwide, several million HTLV-I carriers are at risk for disease, with an
      estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease
      progression are relatively unknown. We studied human leukocyte antigens (HLA
      class II) that have been implicated in the pathogenesis of HTLV-I-related
      diseases. METHODS: We analyzed HLA class II alleles among asymptomatic HTLV-I
      carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I
      seronegative control subjects (n = 51). All participants were of African descent
      and were enrolled in epidemiologic studies conducted at the University of the
      West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays
      for HLA antigen serotyping and polymerase chain reaction-based methods to examine
      HLA class II DRB1 and DQB1 alleles. RESULTS: Two antigens determined by
      serotyping, DR15 and DQ1, occurred at significantly increased frequency among
      HTLV-I carriers compared with seronegative control subjects (42% versus 22% for
      DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78%
      versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were
      shown to have an HLA class II allele distribution similar to that of patients
      with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602
      were significantly greater in patients with ATL and asymptomatic carriers than in
      patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501
      DQB1*0602 were significantly increased among patients with ATL compared with
      patients with HAM/TSP. CONCLUSIONS: These data suggest that host genetic
      background is an important factor in determining whether HTLV-I carriers develop
      either ATL or HAM/TSP.

PMID- 9554446
TI  - Detection of mutations associated with colorectal cancer in DNA from whole-gut
      lavage fluid.

PMID- 9554447
TI  - Re: Biology of cachexia.

PMID- 9554448
TI  - Chemo-hormonal therapy of breast cancer: lack of interaction between lab and
      clinic.

PMID- 9554449
TI  - Re: Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in
      patients with breast cancer.

PMID- 9554450
TI  - Angioimmunoblastic lymphadenopathy with dysproteinemia: emphasis on pathogenesis
      and treatment.
AB  - Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a rare
      lymphoproliferative disorder characterized by diffuse lymphadenopathy, fever,
      hepatosplenomegaly, hemolytic anemia, and polyclonal hypergammaglobulinemia.
      Morphologically, the involved lymph nodes demonstrate complete effacement of the
      normal architecture, prominent neovascularization and infiltration by
      immunoblasts and plasma cells. Other terms that have been used to describe this
      entity include diffuse plasmacytic sarcomatosis, immunoblastic lymphadenopathy,
      lymphogranulomatosis X, and immunologic aberrations in idiopathic reticulosis.
      Initially, AILD was thought to be a disease of B-cell origin that represented
      reactive immune response to unknown stimulus and high potential for malignant
      transformation. It is now evident that AILD in 80% of cases follows an aggressive
      course with short median survival, especially, if complete response with
      chemotherapy is not achieved. Immunologic and molecular studies have demonstrated
      that the majority of AILD cases are T-cell clonal disorders. Despite the numerous
      reports on the role of Epstein-Barr virus in this disorder, it is unknown whether
      the presence of this virus is associated with the immune defect that accompanies
      AILD, or whether it is a pathogenetic factor. In contrast to non-Hodgkin's
      lymphomas, a stage is not usually assigned to the patient since the disease is
      systemic in nature, subsequently, parameters such as extent of disease and tumor
      bulk used to identify high-risk patients with non-Hodgkin's lymphomas, do not
      appear to correlate with disease activity or prognosis in AILD. Treatment of AILD
      has been unsatisfactory, with approximately 25% of patients achieving complete
      and sustained remission when combined chemotherapy agents are used. This article
      is devoted to a discussion of the different manifestations, suggested
      pathogenesis, and treatment of AILD.

PMID- 9554451
TI  - Effects of oxygen and carbon dioxide on mean cell volume.
AB  - Changes in mean cell volume (MCV) following addition of CO2, O2 or both to venous
      blood treated with ethylenediaminetetraacetic acid were studied in an attempt to
      evaluate the effects of saturation with these gases. The MCV before the addition
      was taken to be 100%. When CO2 was mixed with each of 353 samples, the mean
      increase (+/- SD) was 6.10 +/- 1.72%. When O2 was added to 335 specimens, the
      mean decrease was 1.42 +/- 0.96%. When first CO2 and then O2 was added to 266
      samples, the mean change (the sum for each sample of the absolute value of the
      increase plus that of the decrease) was 7.39 +/- 1.90%. Results of samples of
      venous and arterial blood from 15 subjects were compared to check these
      observations in vivo. The MCV of venous blood was always larger than that of
      arterial blood.

PMID- 9554452
TI  - Comparison of progenitor cell content in sequential peripheral blood progenitor
      collections after mobilization with chemotherapy and granulocyte macrophage
      colony-stimulating factor.
AB  - Optimal timing of peripheral blood progenitor cell (PBPC) harvest to collect
      maximal stem cell numbers is unknown. We assessed the progenitor cell content in
      128 PBPC harvests from 21 patients primed with chemotherapy and granulocyte
      macrophage-colony stimulating factor (GM-CSF) in relation to absolute neutrophil
      count (ANC) at collection time. Samples were obtained by leukapheresis during
      rebound from chemotherapy-induced neutropenia while receiving GM-CSF, and assayed
      by flow cytometry for CD34+ and by colony assays for CFU-GM and BFU-E. The CD34+
      cell concentrations per sample tended to be greater at an ANC < 1,000 mm3 and
      decreased with rising ANC (p = 0.001). The CFU-GM and BFU-E concentrations per
      sample remained relatively constant with rising ANC (p = 0.72, p = 0.90,
      respectively). Total CD34+ cell number per harvest per kg slightly increased with
      ANC levels (p = 0.044) whereas the total CFU-GM and the total BFU-E per kilogram
      increased more modestly with rising ANC (p < 0.001, p < 0.001, respectively). We
      conclude that after priming with chemotherapy and GM-CSF, PBPC could be collected
      at different absolute neutrophil counts without greatly affecting total CD34+
      cell numbers. The greater concentration of CD34+ progenitor cells at a lower ANC
      together with the CFU-GM and BFU-E peaking with higher ANC suggest a less mature
      progenitor cell population at lower ANC levels.

PMID- 9554453
TI  - Thromboembolic events in beta thalassemia major: an Italian multicenter study.
AB  - Thromboembolic (TE) events have been frequently reported in beta-thalassemic
      patients in association with known risk factors such as diabetes, complex
      cardiopulmonary abnormalities, hypothyroidism, liver function anomalies, and
      postsplenectomy thrombocytosis. In a recent survey involving 9 Italian
      thalassemic centers, we identified 32 patients with TE episodes in a total of 735
      subjects, of whom 683 had thalassemia major and 52 thalassemia intermedia,
      corresponding to 3.95 and 9.61%, respectively. There was a great variation in
      localization: the main one (16/32) was CNS, with a clinical picture of headache,
      seizures and hemiparesis. Other localizations were the pulmonary (3 patients),
      mesenteric (1 patient) and portal (2 patients) sites. There were 6 cases of deep
      venous thrombosis (2 in the upper limbs, 4 in the lower ones). Intracardiac
      thrombosis was found in 2 subjects and clinical and laboratory signs of DIC were
      observed in 2 others during pregnancy. Since our patients with TE events present
      a statistically significantly higher incidence of associated dysfunction
      (cardiomyopathy, diabetes, liver function anomalies, hypothyroidism) than those
      without TE events (50 vs. 13.8%), we suggest close monitoring of those patients
      who are at higher risk of developing TE events because of the presence of one or
      more of these predisposing factors.

PMID- 9554454
TI  - Six new Gaucher disease mutations.
AB  - Six previously undescribed mutations were identified in 6 unrelated Gaucher
      disease patients: 437C-->T (107Ser-->Leu), 593C-->T (159Pro-->Leu), 604C-->T
      (163Arg-->Stop), 1138G-->A (341Ala-->Thr), 1214G-->A (366Ser-->Asn), 1294T-->A
      (393Trp-->Arg). Five patients were compound heterozygotes and 1 patient was a
      593T/593T homozygote. Four patients had type I Gaucher disease with mild clinical
      phenotypes. Two other patients manifested central nervous system involvement
      (type II and type III).

PMID- 9554455
TI  - Overproduction of antiplatelet antibody against glycoprotein IIb after
      splenectomy in a patient with Evans syndrome resulting in acquired
      thrombasthenia.
AB  - We treated a 33-year-old female with Evans syndrome. She received high dose gamma
      globulin, prednisolone, and azathioprine, and her platelet count transiently
      increased. After splenectomy, the platelet count markedly increased. However, the
      bleeding tendency worsened and the bleeding time was prolonged. A platelet
      defect, characteristic of thrombasthenia, was found. Antigen-captured ELISA and
      Western blotting revealed that the patient's serum had an IgG autoantibody
      against platelet membrane glycoprotein IIb and the patient's plasma inhibited
      normal platelet aggregation. These findings suggest that overproduction of the
      antiplatelet antibody is triggered by platelet recovery due to splenectomy and
      affects platelet function resulting in acquired thrombasthenia.

PMID- 9554456
TI  - Therapeutic efficacy of recombinant interferon-alpha in polycythaemia vera.
AB  - The therapeutic efficacy of recombinant interferon-alpha (rIFN-alpha) has been
      evaluated in 7 patients with polycythaemia vera (PV), diagnosed according to the
      criteria of the Polycythemia Vera Study Group. Six complete responses and one
      partial response were achieved. Pruritus significantly improved in 80% (4/5) of
      the cases. Recombinant interferon-alpha had to be discontinued in 1 patient
      because of grade 3-4 nephrotoxicity according to WHO criteria. rIFN-alpha therapy
      significantly decreased the phlebotomy requirements and improved the mean
      corpuscular volume, erythrocyte and platelet counts, pruritus complaints and the
      degree of splenomegaly (p < 0.05). rIFN-alpha seems to be an effective treatment
      modality for the myeloproliferation of PV and pruritus complaints.

PMID- 9554457
TI  - Translocation t(1;10) (q21;q26) in a case of acute nonlymphocytic leukemia.
AB  - Chromosome banding studies carried out on bone marrow cells from a 16 year-old
      boy with an M1 acute nonlymphocytic leukemia (ANLL) revealed an unbalanced
      translocation involving chromosomes 1 and 10: der(10) t(1;10) (q21;q26) that
      results in a partial trisomy 1q between bands 1q21-1qter. Marker del(6)(q21) and
      trisomies of chromosomes 18, 21 and 22 were also observed. To our knowledge, this
      der(10) is the first to be reported in a patient with ANLL.

PMID- 9554458
TI  - Recurrent breast relapses in a patient with acute lymphoblastic leukaemia
      following allogeneic bone marrow transplantation.
AB  - Isolated extramedullary relapse is very rare after allogeneic bone marrow
      transplantation (BMT) in acute lymphoblastic leukaemia (ALL) and continues to be
      a therapeutic problem. We report recurrent breast relapses in a patient with ALL
      after allogeneic BMT. On both occasions, bone marrow cells were shown to be of
      donor origin and masses disappeared after systemic chemotherapy. Treatment of the
      isolated extramedullary relapse after allogeneic BMT is discussed.

PMID- 9554459
TI  - Bone marrow dysplasia with basophilic cells in a patient with angiocentric
      lymphoma.
AB  - We report a 46-year-old man suffering from angiocentric lymphoma of the skin. On
      admission, he had atypical cells rich in basophilic granules in the bone marrow
      and peripheral blood, in addition to skin eruptions and bone marrow dysplasia.
      Immediately after diagnosis, the patient was treated with multidrug combination
      chemotherapy. At first, the chemotherapy markedly relieved the skin eruption and
      bone marrow dysplasia, and atypical cells in the bone marrow and peripheral blood
      disappeared rapidly. However, the disease gradually became resistant to
      chemotherapy, resulting in a gradual deterioration of the skin eruption and bone
      marrow dysplasia, and reappearance of atypical cells. The levels of serum
      cytokines such as interleukin-4 and interleukin-6, and of soluble interleukin-2
      receptor correlated well with the disease states. These results suggest that the
      lymphoma cells directly or indirectly induce the production of these cytokines
      and that a dysregulated cytokine network, which might be caused by lymphoma
      cells, induces an increase in atypical cells.

PMID- 9554460
TI  - Atypical spontaneous factor VIII inhibitor: specific diagnostics and therapy of
      acute bleeding.
AB  - Differentiation of rapidly binding coagulation factor inhibitors from
      antiphospholipid antibodies is a challenge for the hemostaseologic laboratory,
      especially with respect to the different therapeutic consequences. Several
      immunological and functional assays for the diagnosis of these disorders have
      been proposed. Here we report the clinical and laboratory findings of a 65-year
      old man who developed severe bleeding after a tooth extraction. The process
      leading to the diagnosis of a spontaneous atypical factor VIII inhibitor and the
      value of different laboratory tests are discussed.

PMID- 9554461
TI  - Phase I study of taxol in refractory acute myelogenous leukemias using a weekly
      schedule.

PMID- 9554462
TI  - Usefulness of determining reticulated and large platelets in idiopathic
      thrombocytopenic purpura.

PMID- 9554463
TI  - Pediatric endocrinology update: an overview. The essential roles of estrogens in
      pubertal growth, epiphyseal fusion and bone turnover: lessons from mutations in
      the genes for aromatase and the estrogen receptor.
AB  - The goals of this presentation are to review the essential roles of aromatase,
      estrogens and the estrogen receptor in pubertal growth. Estrogen deficiency due
      to mutations in the aromatase gene (CYP19) and estrogen resistance due to
      disruptive mutations in the estrogen receptor gene have no effect on normal male
      sexual maturation in puberty. However, they lead to absence of the pubertal
      growth spurt, delayed bone maturation, unfused epiphyses, continued growth into
      adulthood and very tall adult stature in both sexes. Gonadotropin and androgen
      levels are elevated in patients with either estrogen deficiency (aromatase
      deficiency) or estrogen resistance (estrogen receptor mutation). Glucose
      intolerance, hyperinsulinemia and lipid abnormalities are also present. Skeletal
      integrity is compromised. Increased bone turnover, reduced bone mineral density
      and osteoporosis develop in both sexes. Sexual orientation is appropriate in
      males and females. In females, aromatase deficiency in the ovary causes pubertal
      virilization and multicystic ovaries because of elevated gonadotropins and
      androgens. Simultaneously, secondary sexual maturation fails to occur. Placental
      aromatase deficiency results in virilization of the mother and her female fetus
      because of the accumulation of potent androgens which are not converted to
      estrogens. The male fetus has normal genitalia. In conclusion, estrogens are
      essential for normal female secondary sexual maturation, bone maturation,
      epiphyseal fusion, pubertal growth spurt and achievement of normal bone mineral
      mass. Estrogens also influence insulin sensitivity and lipid homeostasis.
      However, estrogens do not appear to be essential for fetal survival, placental
      growth, or female sexual differentiation.

PMID- 9554464
TI  - Genetic defects in the control of growth hormone secretion.
AB  - Since growth hormone deficiency (GHD) causes short stature and metabolic
      derangements, the processes which control its release are important
      physiologically. These processes can be illuminated by an understanding of
      genetically determined GHD. In 2 Indian Moslem cousins from a consanguineous
      family, GHD resistant to growth hormone releasing hormone (GHRH) stimulation was
      found. No mutations were found in the growth hormone gene (GH1) (J. Phillips).
      The receptor for GHRH (GHRHR), implicated in the dwarfism of the little mouse,
      thus becomes a candidate gene to explain their GHD. Amplification and sequencing
      a region of GHRHR homologous to that mutated in the little mouse showed a
      mutation (265G*T) leading to a stop codon at position 72 which would completely
      prevent GHRHR expression. Subsequently, Maheshwari et al. found an identical
      mutation in a multiplex kindred from Sindh, Pakistan, about 800 km from the place
      of origin of our patients. GHD is more commonly caused by recessive or dominant
      mutations of GH1. The latter are of great interest in understanding the mechanism
      of GH secretion. In a large kindred with dominant GHD we found a heterozygous
      666G*A mutation replacing of Arg with His at amino acid 183. We speculate that
      the introduced histidine interferes with interactions necessary for correct GH
      secretion.

PMID- 9554465
TI  - Growth hormone therapy update in Thailand.
AB  - There were 841 children in Thailand with growth hormone deficiency (GHD) from
      January 1992 to 1996. Idiopathic isolated GHD was the major diagnosis. Only
      40.19% received recombinant DNA human growth hormone (rhGH) treatment. Also
      reported here is a 1-2 year study of rhGH therapy in 30 GH-deficient children (21
      males, 9 females), aged (mean +/- SD) 10.41+/-3.16 years, and bone age 7.37+/
      3.34 years. The height velocity 1 and 2 years posttreatment were 8.17+/-1.9 and
      7.36+/-2.8 cm/year respectively, which were statistically significant compared to
      pretreatment values of 3.91+/-1.09 cm/ year. Improved height SDS was observed at
      the end of each treatment period. Thyroid function and glycosylated hemoglobin
      tests were normal during the treatment period. There were no reports of side
      effects.

PMID- 9554466
TI  - Review on the physical growth in primates.
AB  - J.M. Tanner concluded in 1962 that the growth velocity curve in body weight shows
      two peaks in primates but only one peak in the other mammals, and that the first
      peak in primates corresponds phylogenetically to the peak in the other mammals.
      Many reports on the physical growth of primates have been accumulated in the past
      70 years. Using some of them as a basis, the author illustrated the normative
      velocity curves (increment curves) of the weight of monkeys, chimpanzees and
      humans, and reconsidered Tanner's conclusion. However, there are still some as
      yet obscure aspects to be interpreted in future.

PMID- 9554467
TI  - The molecular basis of hypopituitarism.
AB  - Pit-1 is a pituitary-specific transcription factor responsible for pituitary
      development and hormone expression in mammals. My laboratory and others have
      recently described several patients with combined pituitary hormone deficiency
      (CPHD) due to point mutations in the pit-1 gene. In addition to pit-1, other
      nuclear factors appear to be necessary for full expression of pituitary genes. A
      zinc finger transcription factor, Zn-15, is responsible with pit-1 for
      synergistic activation of the GH gene. The Pr1 gene is regulated synergistically
      by pit-1 and the estrogen receptor. Finally, the pit-1 gene itself is regulated
      by an enhancer element located > 10 kb upstream of the transcriptional start.
      This element contains several pit-1 DNA binding sites and retinoic acid response
      elements (RAREs). On one of these elements, pit-1 and RAR interact functionally
      to mediate a synergistic response to RA. Recent data from our laboratory suggests
      that RA induction of the pit-1 gene can be impaired by pit-1 gene mutations.
      Study of pit-1 mutations and their diverse pathophysiological mechanisms should
      increase our understanding of anterior pituitary gland development and gene
      regulation in normal and disease states.

PMID- 9554468
TI  - The role of the insulin-like growth factor system in the developing brain.
AB  - Insulin-like growth factors (IGFs) play a central role in brain growth and
      development, with IGF-1, its receptors and binding proteins (IGFBPs) being highly
      expressed, particularly in the olfactory bulb (OB), representing a local
      paracrine system. A potential role of IGFBPs in transporting and targeting IGFs
      to their receptors is supported by the finding that abundant IGFBP-2 is
      associated with cell surface proteoglycans. An OB organ culture system expressing
      IGF-1 and IGFBPs represents an in vitro injury model. Although IGF-1 is potently
      antiapoptotic for neurons and oligodendrocytes, marked gliosis and IGFBP-3
      expression are seen, similar to in vivo injury responses, where intraventricular
      injection of IGF-1 postinjury enhances neuronal survival by blocking apoptosis.
      In contrast, des (1-3) IGF-1, which has low affinity for IGFBPs, is ineffective,
      supporting a transport or receptor targeting role for local IGFBPs. We conclude
      that the IGF system plays a crucial cell survival and growth role in the
      developing and injured brain and that IGFs have significant therapeutic
      potential.

PMID- 9554470
TI  - Growth hormone therapy: a survey.

PMID- 9554469
TI  - Short stature caused by a natural growth hormone antagonist.
AB  - Severe short stature in a male child due to a single mutation in the GH-1 gene
      was first reported in 1996 by Takahashi et al. [N Engl J Med 1996;334:432-436].
      This missense mutation was predicted to convert codon 77 from arginine (R) to
      cysteine (C). The child's chronological age was 4 years and 11 months, and his
      bone age 2 years and 6 months, i.e., equal to only 51% of his chronological age.
      Body proportions were normal except for the prominent forehead and saddle nose.
      Pituitary size was normal on magnetic resonance imaging examinations. Serum IGF
      1, IGFBP-3 and GHBP were all decreased or at the lower limit of the normal range.
      Nocturnal urinary growth hormone (GH) excretion was high. Isoelectric focusing
      analysis revealed the presence of an abnormal GH peak in addition to the normal
      one. The R77C mutant GH possessed a 6 times greater affinity to GHBP than the
      wild-type GH, and inhibited tyrosine phosphorylation in IM-9 cells 10 times more
      potently than the wild-type GH, showing an antagonistic or a dominant negative
      action. In agreement with the antagonistic property of the mutant GH exhibited,
      the child did not show any increase in serum IGF-1 levels after exogenous hGH
      administration. It should be noted that the child in this study is not a typical
      case of Kowarski syndrome in which endogenous GH is found to be simply
      bioinactive, as in the patient we recently described elsewhere. Therefore, this
      patient's condition should be categorized as a new syndrome of short stature
      caused by a natural GH antagonist.

PMID- 9554471
TI  - Growth hormone insensitivity syndrome (Laron dwarfism).

PMID- 9554472
TI  - Recombinant human growth hormone therapy in infants with chronic renal failure.

PMID- 9554473
TI  - Free form of insulin-like growth factor-I in circulation is normal in children
      with simple obesity.

PMID- 9554474
TI  - IGF-1 generation test in non-growth hormone-deficient short children.

PMID- 9554475
TI  - Turner syndrome in Taiwan.

PMID- 9554476
TI  - The role of the GH-N gene abnormality in the development of growth hormone
      deficiency.

PMID- 9554477
TI  - Final height after long-term growth hormone treatment in Thai children with
      Turner syndrome.

PMID- 9554478
TI  - Growth hormone deficiency associated with pituitary stalk interruption syndrome.

PMID- 9554479
TI  - FGFR3 gene mutations in transmembrane domain in Chinese achondroplasia and
      hypochondroplasia patients.

PMID- 9554480
TI  - Determining gene dosage.

PMID- 9554481
TI  - Growth factor involvement in progression of prostate cancer.
AB  - Understanding how the regulation of growth factor pathways alters during prostate
      cancer (PC) progression may enable researchers to develop targeted therapeutic
      strategies for advanced disease. PC progression involves the shifting of cells
      from androgen-dependent growth to an androgen-independent state, sometimes with
      the loss or mutation of the androgen receptors in PC cells. Both autocrine and
      paracrine pathways are up-regulated in androgen-independent tumors and may
      replace androgens as primary growth stimulatory factors in cancer progression.
      Our discussion focuses on growth factor families that maintain homeostasis
      between epithelial and stromal cells in the normal prostate and that undergo
      changes as PC progresses, often making stromal cells redundant. These growth
      factors include fibroblast growth factor, insulin-like growth factors, epidermal
      growth factor, transforming growth factor alpha, retinoic acid, vitamin D3, and
      the transforming growth factor beta families. We review their role in normal
      prostate development and in cancer progression, using evidence from clinical
      specimens and models of PC cell growth.

PMID- 9554482
TI  - Determination of gene dosage at the PMP22 and androgen receptor loci by
      quantitative PCR.
AB  - Although many genetic diseases are caused by the presence of point mutations in
      respective genes, an increasing number of diseases are known to be caused by gene
      copy number changes. We report the development of a rapid and reliable PCR-based
      method for quantitation of gene copy number with sufficient sensitivity to detect
      single copy changes without the use of radioactive or fluorescent labeling. The
      sensitivity of this technique has been demonstrated by the detection of the DNA
      duplication or deletion occurring in two inherited peripheral neuropathies,
      Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to
      pressure palsies (HNPP), that are caused by a reciprocal duplication or deletion
      event on chromosome 17p11.2-12. This method relies on the comparison of the
      amount of PCR product generated from a potentially duplicated or deleted target
      sequence with the amount of product generated from a disomic reference gene. The
      value of this ratio (target PCR product:reference PCR product) indicates whether
      the target sequence is duplicated, deleted, or unchanged. Using primers from
      within a duplicated or deleted region (PMP22 gene and EW401) and from within a
      reference region (NF1 gene), we tested 50 CMT1A, 30 HNPP, and 50 unaffected
      individuals for the presence of a DNA duplication or deletion. TARGET: reference
      ratios of 1.58, 1.02, and 0.56 were detected for the CMT1A, unaffected, and HNPP
      groups, respectively. Thus, differentiation of the three groups of individuals
      was on the basis of gene copy number. This technique was successfully used to
      detect the difference in the X chromosome copy number between males and females
      (target:reference ratios of 1.1 and 2.3, respectively). This approach to the
      detection of DNA duplications and deletions is sensitive, accurate, and has
      potential applications in the quantitation of changes in gene copy number
      associated with diseases characterized by such chromosomal alterations.

PMID- 9554483
TI  - Automated fluorescent analysis procedure for enzymatic mutation detection.
AB  - The Enzymatic Mutation Detection (EMD) assay detects mutations or polymorphisms
      in DNA. The assay procedure takes <1 h and is followed by electrophoretic
      detection. We report an automated procedure, using fluorescently labeled probe
      and quantitative analysis on the ABI Prism 377 DNA Sequencer, that improves on
      earlier methods (1, 2) by eliminating the need for sample purification,
      shortening the hybridization time, and increasing the signal-to-noise ratio. The
      EMD assay uses the bacteriophage resolvase T4 endonuclease VII, which cleaves the
      heteroduplex molecules at the mismatch site, forming two shorter fragments that
      are resolved by gel electrophoresis. Unlike existing mutation techniques, the EMD
      method uses a single protocol to identify point mutations, deletions, and
      insertions for all DNA fragments. Test DNA samples are assayed directly from PCR
      reactions, and fragments up to 4 kb in size have been assayed successfully. A
      independent analysis on the p53 tumor suppressor gene from clinical samples has
      shown 100% sensitivity and 94% specificity. Because the fluorescent EMD assay has
      been optimized for high signal-to-noise ratios, mutations can be identified in
      mixed samples containing up to a 20-fold excess of normal DNA.

PMID- 9554484
TI  - Prenatal and postnatal diagnoses of thalassemias and hemoglobinopathies by HPLC.
AB  - The conventional approach to qualitative and quantitative analyses of hemoglobin
      (Hb) molecules for the diagnoses of hemoglobinopathies requires a combination of
      tests. We used an automated HPLC (VARIANT) system to study alpha-thalassemia and
      beta-thalassemia syndromes in Thailand. The beta-thalassemia short program is
      applicable to the diagnosis of alpha-thalassemia and beta-thalassemia disorders,
      including Hb H, EA Bart's disease, and EF Bart's disease, in adults, newborns,
      and fetuses. The system cannot quantify accurately certain Hb molecules, such as
      Hb H and Hb Bart's. The alpha-thalassemia short program was therefore developed
      and used to quantify Hb Bart's to detect alpha-thalassemia genotypes in cord
      blood. This automated HPLC system is an alternative approach to the diagnosis of
      complicated thalassemia syndromes in Thailand and Southeast Asia.

PMID- 9554485
TI  - Serum protein electrophoresis by CZE 2000 clinical capillary electrophoresis
      system.
AB  - We compared the automated Paragon 2000 clinical capillary zone electrophoresis
      (CZE) system with two manual methods, agarose electrophoresis (AGE) and cellulose
      acetate electrophoresis (CAE). Reference intervals in healthy adults were
      determined for each method. When compared with AGE and CAE, CZE gave
      substantially higher reference values for the alpha1-globulin fraction. With CZE,
      within-run precision for fraction quantitation was between 0.5% (albumin) and
      4.1% (alpha1-globulin). Total precision was between 0.8% (albumin) and 5.3% (beta
      globulin). Data obtained from CZE showed poor linear correlation with results
      obtained by AGE but good linear correlation with data from CAE. Analysis of serum
      from patients with inter alia inflammation, nephrotic syndrome, or polyclonal
      gammopathy showed that clinical information obtained by CZE is comparable with
      information obtained by AGE and CAE. We conclude that CZE offers a clinically
      reliable alternative to AGE and CAE and has the advantages of automation, higher
      precision, and faster turnaround time.

PMID- 9554486
TI  - Detection and classification of paraproteins by capillary
      immunofixation/subtraction.
AB  - A selection of 58 specimens with a monoclonal component identified by
      immunoelectrophoresis and/or immunofixation was analyzed with the
      immunosubtraction procedure on the Paragon 2000 capillary electrophoresis system.
      The capillary system detected 93% of the paraproteins and, using
      immunosubtraction, correctly identified 91% of the paraproteins. Paraproteins
      that were detected by immunofixation and/or immunoelectrophoresis but not by
      capillary electrophoresis were also missed by agarose electrophoresis and
      cellulose acetate electrophoresis. Cellulose acetate electrophoresis was the
      least sensitive method for detection of paraproteins. Only 74% of the monoclonal
      components were detected by this technique, whereas 86% were revealed by agarose
      electrophoresis. In addition to monoclonal paraproteins, we also studied biclonal
      paraproteins and oligoclonal banding. Capillary electrophoresis and
      immunosubtraction correctly detected and identified three specimens containing
      biclonal paraproteins. In one specimen, capillary zone electrophoresis detected
      only one band, whereas agarose gel electrophoresis detected two bands. The
      sensitivity for detection and identification of oligoclonal banding by capillary
      electrophoresis was inferior to immunofixation.

PMID- 9554487
TI  - Multicenter evaluation of the Bayer Immuno I CA 15-3 assay.
AB  - We conducted a multicenter evaluation of the analytical and clinical features of
      the automated Bayer Immuno 1 CA 15-3 assay and compared assay performance to two
      manual tests. Results of the 10-day imprecision study of the Bayer Immuno 1 assay
      pooled across four evaluation sites and three lots of reagent produced total CV <
      or = 4%. Lot-to-lot reproducibility for 26 different lots of reagents and
      calibrators manufactured over a 2-year period was demonstrated (CV, 1.1%).
      Results for the Bayer Immuno 1 assay correlated well with the Biomira TRUQUANT BR
      27.29 and Centocor CA 15-3 RIAs (r > or = 0.94). The upper limit of the reference
      interval for the Bayer Immuno 1 assay was 35.9 kilounits/L (35.9 units/mL);
      values were similar for all methods. Longitudinal monitoring of healthy women
      yielded assay values with an average CV of 11% and 21% for the Bayer Immuno 1 and
      Biomira assays, respectively. The Bayer Immuno 1 assay demonstrated the
      analytical features, intermethod correlation, and long-term performance
      characteristics that are essential for longitudinal monitoring of breast cancer
      patients.

PMID- 9554488
TI  - A competitive reverse transcription-PCR to study apolipoprotein epsilon gene
      expression.
AB  - We developed a rapid and simple competitive reverse transcription-polymerase
      chain reaction for the quantification of apo epsilon mRNA in human monocyte
      derived macrophages. The method was applied, and its reliability was shown in
      patients with the familial lipoprotein disorder, type III hyperlipoproteinemia.
      Type III hyperlipoproteinemic patients express markedly higher concentrations of
      apo epsilon mRNA when compared with healthy controls. Patients with this disease
      are usually (>90%) homozygous for a receptor binding-defective isoform of
      apolipoprotein apo E (apo E2). The higher expression of apo epsilon mRNA in the
      patients could, therefore, be a physiological mechanism to compensate for
      functionally defective apo E. The developed procedure might be valuable in
      assessment of apo epsilon gene expression in human disease.

PMID- 9554489
TI  - Reference standardization and triglyceride interference of a new homogeneous HDL
      cholesterol assay compared with a former chemical precipitation assay.
AB  - A homogeneous HDL-c assay (HDL-H), which uses polyethylene glycol-modified
      enzymes and sulfated alpha-cyclodextrin, was assessed for precision, accuracy,
      and cholesterol and triglyceride interference. In addition, its analytical
      performance was compared with that of a phosphotungstic acid (PTA)/MgCl2
      precipitation method (HDL-P). Within-run CVs were < or = 1.87%; total CVs were <
      or = 3.08%. Accuracy was evaluated in fresh normotriglyceridemic sera using the
      Designated Comparison Method (HDL-H = 1.037 Designated Comparison Method + 4
      mg/L; n = 63) and in moderately hypertriglyceridemic sera by using the Reference
      Method (HDL-H = 1.068 Reference Method - 17 mg/L; n = 41). Mean biases were 4.5%
      and 2.2%, respectively. In hypertriglyceridemic sera (n = 85), HDL-H
      concentrations were increasingly positively biased with increasing triglyceride
      concentrations. The method comparison between HDL-H and HDL-P yielded the
      following equation: HDL-H = 1.037 HDL-P + 15 mg/L; n = 478. We conclude that HDL
      H amply meets the 1998 NCEP recommendations for total error; its precision is
      superior compared with that of HDL-P, and its average bias remains below +/-5% as
      long as triglyceride concentrations are < or = 10 g/L and in case of moderate
      hypercholesterolemia.

PMID- 9554490
TI  - Analytical approaches of European Union laboratories to drugs of abuse analysis.
AB  - We report a survey on urine drug testing within a total of 269 laboratories of
      the European Union. Clinical laboratories predominated over forensic laboratories
      (59.5% vs 28.5%). Screening without identification/quantification was the common
      approach used by clinical laboratories, whereas screening with
      identification/quantification was the approach used by almost all forensic
      laboratories. Screening was primarily performed by immunoassay in both types of
      laboratories. Gas chromatography coupled to mass spectrometry was the main
      analytical method used for specific identification/quantification of drugs, but
      other methods (including immunoassays) were also used. Cutoff values applied
      varied by laboratory type, country, and method used. A high percentage of
      laboratories did not use or report cutoff values. Overall, countries of the
      European Union vary significantly in regards to drugs tested, analytical
      approach, and screening and identification cutoff values. It is recommended to
      clearly state the analytical method and the cutoff values used when reporting
      results for drugs of abuse testing.

PMID- 9554491
TI  - Zinc protoporphyrin as screening test in female blood donors.
AB  - Erythrocyte zinc protoporphyrin (ZPP) was measured in 102 women blood donors to
      evaluate its usefulness in screening for evolving iron deficiency anemia, a
      reason for the deferral of donors. The results were compared with serum ferritin
      determinations. Five women were deferred before their first donation and eight
      women were deferred after one or two donations. Women with increased ZPP values
      all had low serum ferritin concentrations, indicating iron-deficient
      erythropoiesis that was caused by iron depletion. The positive predictive value
      of an increased ZPP in predicting deferral of the donor after one or two
      donations was 75%, whereas a serum ferritin concentration < or = 12 microg/L
      predicted deferral in 26% of the donors. The results indicate that the ZPP test
      can be recommended as a feasible and inexpensive predonation test to determine a
      subset of donors with iron-deficient erythropoiesis at risk of developing iron
      deficiency anemia.

PMID- 9554492
TI  - A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes
      significantly with intact PTH commercial assay measurements in uremic samples.
AB  - We have previously shown that the Nichols assay for intact parathyroid hormone (I
      PTH) reacts with a non-(1-84) molecular form of PTH. This form behaves as a
      carboxy-terminal fragment and accumulates in renal failure, accounting for 40-60%
      of the measured immunoreactivity. We wanted to see whether this was a common
      event with other commercial two-site I-PTH assays. We thus compared the ability
      of three commercial kits [Nichols (NL), Incstar (IT), and Diagnostic System
      Laboratories (DSL)] to measure I-PTH in 112 renal failure patients and to detect
      hPTH(1-84) and non-(1-84)PTH on HPLC profiles of serum pools from uremic patients
      with I-PTH concentrations of 10-100 pmol/L. The behavior of synthetic hPTH(7-84),
      a fragment possibly related to non-(1-84)PTH was also compared with hPTH(1-84) in
      the three assays. The I-PTH concentrations measured with the three assays in the
      112 uremic samples were highly related (r2 > or = 0.89, P < 0.0001), and the
      values measured with NL were, on average, 23% higher than IT. Values measured
      with DSL were 23% and 56% higher than IT for values less than and more than 40
      pmol/L, respectively. The three assays detected two HPLC peaks on four different
      profiles corresponding to hPTH(1-84) and non-(1-84)PTH. This last peak
      represented 36 +/- 8.4% of the immunoreactivity with NL, 24 +/- 5.5% with IT, and
      25 +/- 2.8% with DSL (NL vs IT or DSL: P < 0.05). These differences were
      confirmed by a 50% lower immunoreactivity to hPTH(7-84) compared with hPTH(1-84)
      for IT and DSL but not for NL. These results suggest that most of the two-site I
      PTH assays would cross-react with non-(1-84)PTH material, thus explaining about
      one-half of the 2-2.5 x higher I-PTH concentrations reported in uremic patients
      without bone involvement than in subjects without uremia.

PMID- 9554493
TI  - Determination of free and total carnitine with a random-access chemistry
      analyzer.
AB  - Carnitine deficiency presents as a major problem in fatty acid oxidation. The use
      of a plasma carnitine assay can rapidly help to describe this deficiency. The
      method we describe here requires two simple steps of sample preparation, followed
      by automated analysis with the Beckman Synchron CX4 random-access chemistry
      analyzer. The goal of this method development was to reduce the cost of analysis
      and to allow a greater number of laboratories to perform this assay on demand
      within 1 h for both free and total carnitine. The method has a linearity of 0-150
      micromol/L and a detection limit of 5 micromol/L. The inter- and intraday CVs are
      <20%. The method agreed closely with both the widely used RIA and
      spectrophotometric methods.

PMID- 9554494
TI  - Direct determination of urinary iodine by inductively coupled plasma mass
      spectrometry using isotope dilution with iodine-129.
AB  - An inductively coupled mass spectrometric method was developed for the direct
      determination of iodine in urine. The application of isotope dilution analysis
      with added 129I offers new possibilities for automatic and accurate
      determinations. The sample preparation consists of dilution with an ammonia
      solution containing 129I. The validation was made by comparison with the results
      obtained in another laboratory by a spectrophotometric method based on the
      Sandell-Kolthoff reaction. Different regression models, including maximum
      likelihood estimation, were used to compare the methods. None of the models
      revealed analytical bias between the two methods. The urine samples analyzed for
      validation were from three persons previously exposed to an iodine bath and
      covered a concentration range of 0.2 to 2.8 micromol/L. A detection limit of 0.02
      micromol/L, a within-run CV of 2.5%, and a between-run CV of 11.9% were estimated
      for the proposed method.

PMID- 9554495
TI  - Fully automated assay for total homocysteine, cysteine, cysteinylglycine,
      glutathione, cysteamine, and 2-mercaptopropionylglycine in plasma and urine.
AB  - We describe a 6-min HPLC method to measure the total concentrations of the most
      important thiols in plasma and urine--cysteine, homocysteine, cysteinylglycine,
      and glutathione--as well as the concentrations in plasma and urine, respectively,
      of cysteamine and 2-mercaptopropionylglycine, two compounds used to treat
      disorders of cysteine metabolism. Precolumn derivatization with bromobimane and
      reversed-phase HPLC were performed automatically by a sample processor.
      Throughput was up to 100 samples in 24 h. The within-run CV ranged from 0.9% to
      3.4% and the between-run CV ranged from 1.5% to 6.1%. Analytical recovery was 97
      107%, with little difference between plasma and urine samples. The detection
      limit was approximately 50 nmol/L for all the analytes studied. Thiol
      concentrations were determined in the plasma of 206 healthy donors and in the
      urine of 318 healthy donors distributed for age and sex. Mean values of plasma
      cysteine and homocysteine were significantly lower in infants (ages, <1 y)
      compared with other age groups (P <0.005). In adults, mean plasma homocysteine
      values were higher in males than in females (9.2 vs 6.7 micromol/L, P <0.0001)
      and in the 6- to 10-year-old group (P <0.05). Mean values for glutathione and
      cysteinylglycine were not sex- and age-dependent. In urine, both cysteine and
      homocysteine showed a wide range of variation.

PMID- 9554496
TI  - Clinical laboratory test menu changes in the Pacific Northwest: 1994 to 1996.
AB  - Laboratory testing services are presently undergoing dynamic changes in response
      to a wide range of external factors. Government regulations, reimbursement, and
      managed care are only a few of the influences affecting the availability of
      testing services and on-site testing capabilities in hospital, independent, and
      physician office laboratories. Medical practice changes, marketplace influences,
      test technologies, and costs also play a role in determining where testing is
      being performed. To better understand the factors influencing clinical laboratory
      test volumes and menus and to identify on-site testing deemed essential in
      physician office laboratories, we gathered information from a network of clinical
      laboratories in the Pacific Northwest. Questionnaires were sent to 257 Laboratory
      Medicine Sentinel Monitoring Network participants in March 1996. In the past 2
      years, changes in on-site test volumes and test menus have been primarily due to
      medical practice changes and marketplace influences. When laboratories had a
      decrease in test volumes or test menu choices, the size of the patient workload
      and the volumes of test orders have had the greatest impact. Laboratory
      regulations and managed care contracts have played a role in shifting on-site
      testing to outside sources; however, these factors did not appear to be primary
      influences. Only 5% of physician office laboratories identified tests that they
      believed were essential for optimal patient care but did not perform on-site.

PMID- 9554497
TI  - A stochastic approximation method for assigning values to calibrators.
AB  - A new procedure is provided for transferring analyte concentration values from a
      reference material to production calibrators. This method is robust to
      calibration curve-fitting errors and can be accomplished using only one
      instrument and one set of reagents. An easily implemented stochastic
      approximation algorithm iteratively finds the appropriate analyte level of a
      standard prepared from a reference material that will yield the same average
      signal response as the new production calibrator. Alternatively, a production
      bulk calibrator material can be iteratively adjusted to give the same average
      signal response as some prespecified, fixed reference standard. In either case,
      the outputted value assignment of the production calibrator is the analyte
      concentration of the reference standard in the final iteration of the algorithm.
      Sample sizes are statistically determined as functions of known within-run signal
      response precisions and user-specified accuracy tolerances.

PMID- 9554498
TI  - Intrinsic and routine quality of serum total potassium measurement as
      investigated by split-sample measurement with an ion chromatography candidate
      reference method.
AB  - We evaluated the intrinsic quality of eight routine test systems for the
      measurement of serum total potassium (K+), as well as the routine quality of four
      of these systems, using a group of 60 single-donation serum samples that had been
      certified with an ion chromatography reference method. The intrinsic quality of
      the tests was evaluated by analysis of the sera in the manufacturers' application
      laboratories under strict internal quality control. The routine quality was
      evaluated by analysis of the same sera in five (per system) routine laboratories
      under daily working conditions. The results of the study were interpreted in
      light of the most stringent specifications derived from the biological variation
      of K+, which require limits of 6.3% for total error and 1.6% for systematic
      error. The study revealed that the intrinsic quality of all systems was
      excellent. None of the test systems yielded a substantial number of results
      outside the 6.3% total error limit, and only one test system exceeded the 1.6%
      systematic error limit. The majority of the routine laboratories reproduced the
      manufacturers' intrinsic quality. In particular, most laboratories satisfied the
      6.3% total error limit. However, several laboratories exceeded the 1.6%
      systematic error limit. Generally, there was a considerable difference in quality
      between the participating laboratories. This showed that the major problems for
      serum K+ analysis (for samples with no unusual matrices and with concentrations
      within the reference interval) are at the routine laboratory.

PMID- 9554499
TI  - Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV
      infected patients.
AB  - An alternative pathway of Trp metabolism involves the conversion of Trp to
      kynurenine by indoleamine-2,3-dioxygenase, which leads to synthesis of the
      neurotoxin, quinolinic acid. This study explores the relationship of indoleamine
      2,3-dioxygenase activity with stages of HIV infection. Sera from 206 HIV-positive
      and 72 seronegative subjects were analyzed for Trp and kynurenine. The kynurenine
      to-Trp (KT) ratio was calculated. The mean KT ratio of seronegative controls was
      36.6 +/- 10.9, and the median ratio was 34.9. The upper limit of the seronegative
      KT ratio, defined as mean + 2 SD, was 58.4. Patients with HIV infection showed a
      reciprocal relationship between the KT ratio, the CD4 count, and the stage of the
      disease. The median KT ratios for asymptomatic and AIDS patients were 50.5 and
      117.0, respectively. This study shows that the serum Trp concentration is
      markedly decreased and that the kynurenine concentration is increased with immune
      stimulation in HIV infection. This may lead to changes in quinolinic acid and
      explain some of the pathogenesis of AIDS dementia.

PMID- 9554500
TI  - Evaluation of an acidic deproteinization for the measurement of ascorbate and
      dehydroascorbate in plasma samples.
AB  - The most popular pretreatment method of plasma samples for the measurement of
      ascorbate (AsA) and dehydroascorbate (DHA) has been an acidic deproteinization
      via metaphosphoric acid or trichloroacetic acid. In general, DHA is absent in
      plasma samples prepared from human blood in a conventional manner. However, when
      these plasma samples were subjected to acidic deproteinization, DHA was detected
      in the acidified sample solutions. In the present study, we demonstrate that the
      oxidation of AsA to DHA in the solutions was promoted by at least two mechanisms,
      one involving catalysis by ferric ion released from transferrin, and the other
      involving catalysis by plasma hemoglobin. In the acidified transferrin solution
      by trichloroacetic acid, an oxidation of AsA to DHA proceeded with standing time,
      whereas the oxidation was not observed in that by metaphosphoric acid. This
      oxidation appeared to be catalyzed by ferric ion released from transferrin. In
      contrast, plasma hemoglobin functioned as a catalyst for AsA oxidation in both
      metaphosphoric acid and trichloroacetic acid solutions. Therefore, DHA content in
      the trichloroacetic acid-treated plasma sample was markedly higher than that in
      the metaphosphoric acid-treated one. These results suggest that DHA detected in
      acidified plasma samples is an artifact resulting from AsA oxidation.

PMID- 9554501
TI  - Simple DNA probe assays based on particle agglutination.

PMID- 9554502
TI  - Evaluation of proficiency survey results for serum immunoglobulins following the
      introduction of a new international reference material for human serum proteins.

PMID- 9554503
TI  - PCR conditions and DNA denaturants affect reproducibility of single-strand
      conformation polymorphism patterns for BRCA1 mutations.

PMID- 9554504
TI  - Measurements of total and desialylated sex hormone binding globulin in serum by
      ELISA.

PMID- 9554505
TI  - The use of a whole-blood benchtop analyzer (Nova 16) in a cardiac STAT intensive
      care unit.

PMID- 9554506
TI  - Rapid and sensitive gas chromatography-mass spectroscopy method for the detection
      of mannitol and sorbitol in serum samples.

PMID- 9554507
TI  - Measurement of the total antioxidant activity of human aqueous humor.

PMID- 9554508
TI  - Cardiac troponin I in myocardial contusion.

PMID- 9554509
TI  - Combined use of markers of muscle necrosis and fibrinogen conversion in the early
      differentiation of myocardial infarction and unstable angina.

PMID- 9554510
TI  - More on interference of N-acetylcysteine in measurement of acetaminophen.

PMID- 9554511
TI  - Toxic levels of acetaminophen produce a major positive interference on Glucometer
      Elite and Accu-chek Advantage glucose meters.

PMID- 9554512
TI  - Why "urea nitrogen" when urea is measured?

PMID- 9554513
TI  - Total and non-protein-bound fractions of 3,4-dihydroxyphenylalanine.

PMID- 9554514
TI  - PSA concentrations in seminal plasma.

PMID- 9554515
TI  - Inadequate laboratory technique for amino acid analysis resulting in missed
      diagnoses of homocystinuria.

PMID- 9554516
TI  - Early historical milestones in HDL-cholesterol assay.

PMID- 9554517
TI  - Utilization of polymerase chain reaction technology in the detection of solid
      tumors.
AB  - BACKGROUND: Most cancer detection tests currently performed are based on either
      antibody assays to a marker protein with altered expression in cancer patients or
      on imaging studies to identify characteristic lesions. Generally, for a positive
      result, these detection assays require that a tumor have a significant volume of
      cancer cells. Advances in diagnostic techniques and technology may allow for
      cancer detection at earlier stages, when the tumor burden is smaller and
      potentially more curable. The molecular techniques of polymerase chain reaction
      (PCR) and reverse transcriptase PCR (RT-PCR) are highly sensitive methods for
      detecting a small number of cancer cells. Over the past few years, numerous
      clinical studies have used PCR techniques to detect physical alterations of
      genes, such as mutations, deletions, translocations and amplification, the
      presence of oncogenic viruses, and the expression of genes specific to tissue,
      cancer, and metastasis. The current status of PCR as a method for detecting
      marker genes in the management of solid tumors is reviewed. METHODS: A review of
      the literature on the clinical utility of PCR and RT-PCR in the detection of
      solid tumor micrometastasis was conducted. RESULTS: Amplification by PCR is a
      highly sensitive method to determine gene expression. A single cell expressing a
      tumor marker among 10-100 million lymphocytes can be detected by the PCR assay.
      This approach has been used to detect tumor cells in approximately 18 different
      solid tumor types, with melanoma and carcinoma of the breast and prostate the
      most widely investigated to date. PCR-based assays have been used to detect
      cancer cells in biopsies of solid tissue, lymph nodes, bone marrow, peripheral
      blood, and other body fluids. Several studies have reported a high specificity
      and sensitivity of tumor marker detection and a high correlation between PCR
      results and the presence of metastatic disease. However, in a few studies, PCR
      assays have not consistently demonstrated a higher sensitivity and specificity of
      detection than traditional modalities for many types of cancer. There has been a
      wide range in sensitivity and specificity among the studies, which may be partly
      attributed to the lack of uniformity among the PCR protocols used in different
      studies. CONCLUSIONS: PCR can detect tumor marker-expressing cells that are
      otherwise undetectable by other means in patients with localized or metastatic
      cancer. Reports from various study groups have lacked uniformity in their
      protocols, and this has prevented adequate comparison. The clinical utility of
      this assay as a tool for the prognosis and management of cancer patients remains
      and area of active investigation. PCR is a powerful tool in the study of the
      biology of cancer metastasis and will likely serve as a useful adjunct to
      clinical decision-making in the future.

PMID- 9554518
TI  - Tumor thickness predicts cervical metastasis in patients with stage I/II
      carcinoma of the tongue.
AB  - BACKGROUND: The incidence of cervical metastases after surgery for Stages I/II
      carcinoma of the tongue is 30-40%. Postoperative cervical metastases are an
      adverse prognostic factor for patients with this malignancy. The purpose of this
      study was to evaluate the clinicopathologic factors associated with late cervical
      metastases in patients with carcinoma of the tongue. METHODS: The
      clinicopathologic features of 44 patients with previously untreated Stage I/II
      carcinoma of the tongue were reviewed. All patients were treated with partial
      glossectomy only. RESULTS: Cervical metastases developed in 21 of 44 patients
      within 5 years. Factors significantly associated with the development of cervical
      metastases were invasive growth, differentiation, nuclear polymorphism in the
      deep portion, tumor border, nest formation, infiltrative growth ratio, depth, and
      thickness. No statistical correlations between cervical metastases and age,
      gender, tumor location, clinical stage, Brinkman index, alcohol index, mitosis,
      connective tissue, lymphocytic infiltration, or perineural invasion were found.
      Multivariate analysis demonstrated that only tumor thickness > 4 mm had a
      predictive value for cervical metastasis (risk ratio 9.4; 95% confidence
      interval, 1.5-57.7). CONCLUSIONS: The current study data indicate that patients
      with Stage I/II carcinoma of the tongue > 4 mm in thickness are at increased risk
      for subsequent cervical metastasis. Thus, conservative supraomohyoid neck
      dissection is indicated in patients with Stage I/II carcinoma of the tongue > 4
      mm in thickness.

PMID- 9554519
TI  - Epstein-Barr virus detection in nasopharyngeal tissues of patients with suspected
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein
      Barr virus (EBV). Detection of EBV in biopsy specimens may serve as a tumor
      marker. METHODS: To assess the sensitivity and specificity of the polymerase
      chain reaction (PCR) and in situ hybridization in the diagnosis of NPC, formalin
      fixed, paraffin embedded nasopharyngeal biopsies from patients in Taiwan
      suspected of having NPC were studied. RESULTS: In specimens from 107 patients
      with NPC, EBV was detected by PCR in 97 cases (90.7%) and by EBER in situ
      hybridization in 105 cases (98.1%). In specimens from 61 patients without
      neoplasia, EBV was detected by PCR in 7 cases (11.5%) and by EBER in situ
      hybridization in 0 cases. CONCLUSIONS: These results suggest that although EBV
      DNA may occasionally be detected in nonneoplastic nasopharyngeal tissues, cells
      expressing EBER are not. EBER in situ hybridization may therefore prove to be a
      useful adjunct in the diagnosis of NPC.

PMID- 9554520
TI  - The clinicopathologic significance of small areas unstained by Lugol's iodine in
      the mucosa surrounding resected esophageal carcinoma: an analysis of 147 cases.
AB  - BACKGROUND: Small areas unstained with Lugol's iodine are often observed in the
      mucosa surrounding esophageal carcinomas. METHODS: For light microscopic
      evaluation, the histologic features of 131 small areas unstained by Lugol's
      iodine in 12 selected cases were investigated. For clinicopathologic evaluation,
      the numbers of small areas unstained by Lugol's iodine in the mucosa surrounding
      147 consecutively resected esophageal carcinomas, including these 12 cases, were
      counted. The relation between the incidence of such areas and the development of
      multiple primary cancers in the upper aerodigestive tract was examined together
      with data on the patients' tobacco and alcohol consumption. RESULTS: Ninety-two
      percent (131) of the small areas unstained by Lugol's iodine contained dysplastic
      lesions. Seventeen (12%) of the 147 resected specimens contained fewer than 5
      small unstained areas, whereas 52 (35%) had 6-10 and 78 (53%) had more than 11
      such areas. The incidence of multicentric cancer in the upper aerodigestive tract
      and the average alcohol index scores were significantly higher for patients who
      had more than 11 unstained areas than for patients who had fewer than 5 such
      areas (P < 0.01). CONCLUSIONS: Lugol's iodine staining method is useful for
      detecting groups at high risk of multicentric cancer in the upper aerodigestive
      tract.

PMID- 9554521
TI  - Treatment of patients with advanced gastric carcinoma with a 5-fluorouracil-based
      or a cisplatin-based regimen: two parallel randomized phase II studies.
AB  - BACKGROUND: Although many drug combination therapies have been proposed, there is
      no standard therapy for patients with advanced gastric carcinoma. The superiority
      of combination therapy over monochemotherapy has not been demonstrated
      convincingly. To explore the role of monochemotherapy, the authors evaluated 5
      fluorouracil (5-FU), modulated by 6S-leucovorin (6S-LV) and a cisplatin
      containing regimen, which was comprised of epirubicin, etoposide, and cisplatin
      with the addition of the reversal agent lonidamine (EEP-L). METHODS: After
      stratification according to performance status (PS) and resection of the primary
      tumor, 72 patients with advanced gastric carcinoma were randomized to 2 parallel
      Phase II trials with 5-FU/6S-LV and EEP-L, respectively. Thirty-six patients in
      Study A received bolus 6S-LV, 100 mg/m2, followed by bolus 5-FU, 370 mg/m2, on
      Days 1-5 and 36 others in Study B received epirubicin, 30 mg/m2, on Days 1 and 5;
      etoposide, 100 mg/m2, on Days 1, 3, and 5; cisplatin, 30 mg/m2, on Days 2 and 4;
      and lonidamine, 150 mg/day. RESULTS: There were 6 partial responses (18.2%) (95%
      confidence interval [CI] +/- 13.2) in Study A and 7 partial responses (21.9%)
      (95% CI +/- 14.3) in Study B. Partial responses were more frequent in patients
      with resected tumors or with an Eastern Cooperative Oncology Group PS of 0-1. The
      median duration of response was 8.8 and 8.3 months, respectively, in Study A and
      Study B. The median survival reached 8 months in Study A and 9 months in Study B.
      In the whole population of patients survival was significantly higher in patients
      with a PS of 0-1 (P < 0.05). Patients with a PS of 0-1 and a resected tumor had
      the significantly longest survival both in EEP-L treated patients and in all
      evaluable patients in the two studies. The most frequent World Health
      Organization Grade 3-4 toxic effects were gastrointestinal in Study A and
      hematologic in Study B. No treatment-related death was observed. CONCLUSIONS: The
      efficacy of 5-FU, modulated with 6S-LV, is moderate in patients with advanced
      gastric carcinoma, similar to cisplatin-containing regimens. PS and other
      prognostic factors could influence the response rate, which does not appear to be
      a reliable parameter for evaluating the outcome of chemotherapy trials.

PMID- 9554522
TI  - Interrelation between tumor-associated cell surface glycoprotein and host immune
      response in gastric carcinoma patients.
AB  - BACKGROUND: Expression of changes in cell surface glycoprotein may correlate with
      the malignant potential and development of gastric carcinoma. Immunologic defense
      mechanisms of the host against the tumor can be effective in preventing the
      development of gastric carcinoma. The authors studied the effects of immunologic
      defense of the host against the tumor, using infiltration of S-100 protein
      positive dendritic cells (DC) as a marker. In cases with or without changes in
      the surface glycoprotein of tumor cells, determinations were made by binding of
      Helix pomatia agglutinin (HPA). METHODS: Paraffin blocks of 123 gastric carcinoma
      specimens were prepared for immunohistochemical staining with the antibody
      against HPA and S-100 protein. Clinicopathologic factors and patient prognosis
      were examined for each indicator. RESULTS: Patients with HPA positive tumors had
      a more aggressive character in several important prognostic aspects and poorer 5
      year survival rates compared with patients with HPA negative tumors. The degree
      of infiltration of DC had no particular correlation with pathologic factors, and
      there was no significant difference between the prognosis of patients with slight
      and marked DC infiltration. In the HPA negative patients there was no significant
      difference in the 5-year survival rates between patients with slight and marked
      DC infiltration; however, in the HPA positive patients the 5-year survival rates
      of patients with marked infiltration of DC were higher. Further investigation
      showed that patients with marked DC infiltration had better 5-year survival rates
      than patients with slight DC infiltration, especially in patients with HPA
      positive and histologically advanced disease. CONCLUSIONS: Patients with a higher
      immunologic defense against cancer cells, as indicated by marked infiltration of
      DC, had a better prognosis in cases of gastric carcinomas of highly malignant
      potential, as indicated by a positive HPA.

PMID- 9554523
TI  - Factors associated with the use of flexible sigmoidoscopy as a screening test for
      the detection of colorectal carcinoma by primary care physicians.
AB  - BACKGROUND: Despite current recommendations of flexible sigmoidoscopy as a
      screening test for the detection of colorectal carcinoma, relatively few
      asymptomatic patients undergo this procedure. To enhance the use of
      sigmoidoscopy, differences in the use of screening, as well as barriers to
      screening among specific physician groups, should be defined. METHODS: The
      authors surveyed 1762 practicing primary care physicians to determine their self
      reported ability to perform sigmoidoscopy and perceived obstacles to either
      initiating or enhancing screening. RESULTS: A total of 884 physicians (50%)
      responded. Ninety percent of primary care physicians reported that they offered
      sigmoidoscopic screening to their patients, with 46% referring patients and 44%
      performing the procedure themselves. Physician characteristics were not
      associated with the overall use of sigmoidoscopy. In contrast, compared with
      physicians who referred patients for the procedure, physicians who performed
      sigmoidoscopy themselves were more often board certified, male, and graduated
      from medical school after 1970 (P < 0.001). In a multivariate analysis, these
      characteristics were also independently associated with the ability to perform
      sigmoidoscopy. The barrier to sigmoidoscopy cited most often was poor patient
      acceptance, whether or not the physician performed or referred patients for
      sigmoidoscopic screening. Other barriers cited were lack of training, lack of
      equipment, and time required, each of which was identified most often by
      physicians who did not screen at all. CONCLUSIONS: Most physicians surveyed
      reported using sigmoidoscopic screening to some degree in their practice,
      although many did not perform the procedure themselves. Population-based
      interventions to increase screening may benefit from targeting specific physician
      subgroups and attempting to improve patient acceptance of the procedure.

PMID- 9554524
TI  - Lymph node harvest reporting in patients with carcinoma of the large bowel: a
      French population-based study.
AB  - BACKGROUND: In patients with resected colorectal carcinoma, lymph node
      involvement has particular importance for patient prognosis and adjuvant therapy.
      The network of French cancer registries (FRANCIM) established a study aimed at
      analyzing the validity of lymph node harvest reporting in a population-based
      sample. METHODS: The study population was comprised of 1081 resected tumors
      without distant visceral metastasis and classified using the TNM system.
      Correlation between the number of examined lymph nodes and the staging of the
      tumor was examined by logistic regression analysis to establish an estimate of
      the minimum number of lymph nodes required to determine whether a tumor is lymph
      node negative. RESULTS: An average of 7.7 +/- 0.2 lymph nodes were examined per
      specimen in the 851 patients for whom the number of lymph nodes examined was
      known. The proportion of cases classified as N+ increased significantly with the
      number of examined lymph nodes (chi-square trend = 24.6; P < 0.0001). If the
      probability of correct lymph node status assessment is 1 in the reference group
      (comprised of pathology reports of specimens with > or = 16 examined lymph
      nodes), the probability of correct N+/N- dichotomization was significantly < 1
      for the 1 to 3 lymph nodes group and the 4 to 7 lymph nodes group (i.e., 53.7% of
      cases). CONCLUSIONS: To comply with current rules for adjuvant chemotherapy,
      surgeons must provide pathologists with at least eight lymph nodes for optimal
      N+/N- dichotomization to reduce the risk of misclassification and understaging.

PMID- 9554525
TI  - The establishment of a preoperative diagnosis of pancreatic carcinoma using cell
      specimens from pancreatic duct brushing with special attention to p53 mutations.
AB  - BACKGROUND: Previously, the authors reported that 82% of cases of pancreatic
      carcinoma were positive for p53 in cytologic specimens obtained by selective
      endoscopic pancreatic duct brushing (SEPB). However, there was an extreme
      discrepancy between the authors' data of p53 overexpression using cytologic
      specimens and other reports using surgically resected specimens. In this study,
      the authors demonstrate that p53 positive cells precisely reflect its gene
      mutations, and also establish systematic procedures for the preoperative
      diagnosis of patients with pancreatic carcinoma. METHODS: The authors examined 44
      cases of pancreatic carcinoma, 30 cases of chronic pancreatitis, and 9 cases of
      papillary adenoma. In all cases, pathologic diagnosis was made by surgery or
      autopsy. The conventional cytology and p53 immunocytology were performed
      simultaneously in the cell specimens obtained by SEPB. In the cases immunostained
      for p53, DNA was extracted selectively from p53 immunostained cells using a light
      microscope. p53 mutations in exons 5 to 8 were examined by direct sequencing.
      RESULTS: Forty of 44 pancreatic carcinomas (91%) were diagnosed correctly by the
      methods of conventional cytology associated with p53 immunocytology. p53
      mutations were detected in 12 of 14 cases that were positive for p53 (86%). Four
      of six cases that were inoperable due to massive metastasis or invasion had the
      mutation at codon 273 (CGT to CAT) in exon 8. CONCLUSIONS: These results suggest
      that p53 immunocytology reflects its gene mutations precisely, and that the point
      mutation at codon 273 (CGT to CAT) of p53 may play an important role in the
      invasive potential and metastasis of pancreatic carcinoma.

PMID- 9554526
TI  - Estrogen-receptor-related protein p29 in primary nonsmall cell lung carcinoma:
      pathologic and prognostic correlations.
AB  - BACKGROUND: Estrogen-dependent intracellular processes are important in the
      growth regulation of normal tissue and may play a role in the regulation of
      malignancies. Utilization of estrogen receptor assays in breast carcinoma is well
      established, but the role of such evaluation in other cancers largely is unknown.
      In this study, immunohistochemical expression of estrogen receptor (ER) and the
      ER-related protein p29 was correlated with survival of patients with nonsmall
      cell carcinoma of the lung. METHODS: All patients with a tissue diagnosis of
      primary nonsmall cell bronchogenic carcinoma diagnosed over a 6-year period at
      the Medical Center Hospital of Vermont were reviewed. Assays for p29 and ER using
      a streptavidin-biotin immunoperoxidase method were performed on each tumor.
      Results were correlated with clinical data, including survival. RESULTS: Of 111
      tumors examined, 109 (98%) were positive for p29 whereas none of the tumors
      reacted with ER (ER1D5). The relation between p29 expression and survival time
      was different for men and women. A statistically significant negative relation
      for women was observed; this relation was most pronounced in patients with Stage
      I and II tumors. A positive but not statistically significant relation was
      observed for men. CONCLUSIONS: The ER-related protein p29 commonly is expressed
      in nonsmall cell carcinomas of the lung. The relation between p29 and survival
      time is different for males and females, suggesting the presence of gender
      specific factors that may influence tumor growth and overall patient survival,
      especially in patients with early stage lung carcinoma.

PMID- 9554527
TI  - Primary systemic amyloidosis with delayed progression to multiple myeloma.
AB  - BACKGROUND: Primary systemic amyloidosis (AL) and multiple myeloma both are
      clonal plasma cell proliferative disorders. Although 10-15% of patients with
      myeloma have coexisting primary amyloidosis, it is unusual for patients with
      primary amyloidosis to progress to myeloma at a later date. The authors describe
      a case series of six patients in whom such progression occurred. METHODS: A
      computerized search was done of the medical records of all patients seen at the
      Mayo Clinic between January 1, 1960 and December 31, 1994 with a diagnosis of AL.
      Of 1596 patients with AL, 6 patients (age range, 60-74 years; median age, 68
      years) with biopsy-proven AL were reviewed in whom delayed (at least 6 months
      after the diagnosis of AL) progression to multiple myeloma occurred. RESULTS: At
      the time of the diagnosis of AL, none of the six patients had evidence of
      multiple myeloma. The dominant manifestation of AL was peripheral neuropathy in
      three patients and cutaneous AL, renal AL, and amyloid arthropathy in one patient
      each. The diagnosis of multiple myeloma was made 10-81 months after the diagnosis
      of AL, based on the demonstration of multiple osteolytic lesions (4 patients) or
      marked bone marrow infiltration (> or = 50%) by plasma cells (5 patients). Two
      patients had received chemotherapy (melphalan and prednisone) for AL. Five
      patients received chemotherapy (four patients) or high dose methylprednisolone
      (one patient) after the diagnosis of multiple myeloma. Five patients died, and
      the median actuarial survival after the diagnosis of multiple myeloma was 20
      months. Multiple myeloma was the cause of death in four patients; one patient
      died of systemic amyloidosis. In 2 patients death occurred within 3 months.
      CONCLUSIONS: AL occasionally progresses to overt multiple myeloma. These cases
      usually occur in patients without significant cardiac or hepatic AL who live long
      enough to develop multiple myeloma.

PMID- 9554528
TI  - Assessment of pulmonary and cardiac function after high dose chemotherapy with
      BEAM and peripheral blood progenitor cell transplantation.
AB  - BACKGROUND: Limited information is available regarding the cardiac and pulmonary
      effects of high dose chemotherapy (HDCT) and autologous peripheral blood
      progenitor cell (PBPC) transplantation. METHODS: The authors evaluated cardiac
      and pulmonary function after BEAM (BCNU 300 mg/m2, etoposide 400 mg/m2/day x 3
      days, cytosine arabinoside 200 mg/m2/day x 4 days, and melphalan 140 mg/m2),
      HDCT, and PBPC transplantation in 26 patients with non-Hodgkin's lymphoma or
      Hodgkin's disease. Therapy prior to BEAM included doxorubicin (25 patients),
      bleomycin (6 patients), and mediastinal irradiation (4 patients). All patients
      had pulmonary function tests (PFTs) and equilibrium radionuclide angiography
      before and at a median of 57 weeks after transplantation. RESULTS: Prior to high
      dose therapy, 8 patients had abnormal PFTs, including 6 with a diffusing capacity
      of the lung for carbon monoxide (DLCO) <70% of predicted value. At the time of
      reevaluation after HDCT, all patients included in the study were in complete
      remission, and none had received additional therapy after transplantation. At a
      median of 77 weeks after transplantation, none of the patients had cardiac or
      pulmonary symptoms. Moreover, there were no significant changes in total lung
      capacity, forced vital capacity, forced expiratory volume in 1 second/forced
      vital capacity, DLCO, or left ventricular ejection fraction values when compared
      with baseline studies. CONCLUSIONS: The authors concluded that HDCT with BEAM and
      PBPC transplantation did not result in significant cardiac or pulmonary toxicity,
      even in patients with borderline pretransplantation PFT values. Further studies
      of patients undergoing HDCT and PBPC transplantation are needed.

PMID- 9554529
TI  - Expression of c-met is a strong independent prognostic factor in breast
      carcinoma.
AB  - BACKGROUND: The c-met protooncogene encodes the met protein, the receptor for
      scatter factor/hepatocyte growth factor, a growth factor that modulates the
      motility and stable interaction of the epithelial cells. This study assesses the
      expression of met receptor in breast carcinoma and its prognostic value with
      respect to survival. METHODS: Immunofluorescence was used to evaluate 91 archival
      breast carcinoma specimens using a polyclonal antibody to the cytoplasmic domain
      of the receptor. Cases were scored by two pathologists on a percentage basis and
      then converted to binary scores (positive or negative) on the basis of a bimodal
      distribution. RESULTS: Strong expression of met was found in 20 invasive ductal
      breast tumor specimens (22%). The 5-year survival of patients whose tumors showed
      decreased met expression was 89%, in contrast to a 52% 5-year survival rate in
      patients whose tumors expressed met (P = 0.008). This trend also was observed in
      patients without lymph node metastases at presentation, in whom met negative
      patients had a 95% 5-year survival compared with only 62% for met positive
      patients (P = 0.006) Multivariate analysis using the Cox proportional hazards
      model showed met expression to be an independent predictor of survival, with a
      predictive value nearly equivalent to that associated with lymph node status.
      CONCLUSIONS: The authors conclude that expression of met in patients with
      invasive ductal carcinoma of the breast is a strong, independent predictor of
      decreased survival and may be a useful prognostic marker with which to identify a
      subset of patients with more aggressive disease.

PMID- 9554530
TI  - Results of intermediate measures from a population-based, randomized trial of
      mammographic screening prevalence and detection of breast carcinoma among Asian
      women: the Singapore Breast Screening Project.
AB  - BACKGROUND: Although increasing rates of breast carcinoma incidence have been
      observed in Asian countries, appropriate strategies for detecting early stage
      breast carcinoma in such communities have been difficult to formulate,
      particularly because no large population screening trial specifically involving
      Asian women has been reported. The objective of this study was to evaluate the
      effectiveness and quality of mammography as a screening technique for Singaporean
      women, who are predominantly Chinese. METHODS: In this prospective study, 166,600
      women in Singapore ages 50-64 years were randomized to either 2-view mammography
      without physical examination (67,656) or observation (97,294, controls) over 2
      years. RESULTS: Of these women, 28,231 (41.7%) responded and were screened; they
      were more likely to be married, have more formal education, be working, be
      Chinese, and be in a higher socioeconomic group (P < 0.001 for all variables). To
      assess for response bias that could affect outcome, results were also evaluated
      for nonrespondents (n = 39,425). The incidence rate of cancers among
      nonrespondents (1 per 1000 woman-years) was less than the 1.3 in women not
      invited to have screening (P = 0.03, relative risk [RR], 1.3; 95% confidence
      interval [CI], 1.0-1.7). However, cancers arising from nonrespondents did not
      differ significantly in stage distribution when compared with cancers within the
      control group. For every 1000 women screened, 4.8 cancers were detected. The
      prevalence ratio (the number of cancers detected per 1000 women at first
      screening divided by the corresponding incidence rate in controls per year) was
      3.6 for screened women and 2.4 for women invited to have screening. The majority
      of cancers detected through screening were early stage, with 64% as either ductal
      carcinoma in situ (26%) or Stage I disease (38%) and was significantly more than
      the corresponding 26% in women not invited to have screening (P < 0.001). When
      only invasive cancers were considered, screened women still had more early
      cancers, with 65% having no lymph node involvement, compared with 47% in the
      group not invited to have screening (P = 0.001; RR, 1.4; 95% CI, 1.2-1.7). Women
      who were screened had half the risk of having Stage II or later cancers (P <
      0.0001; RR, 0.5; 95% CI, 0.4-0.7) when compared with women not invited to have
      screening. This higher detection rate of early cancers through screening was
      accomplished with acceptable recall rates of 8% for further mammographic films or
      physical examination and a biopsy rate of 1.0% (10 per 1000 women screened). The
      interval cancer rate was 2.1 per 10,000 women screened in the first year of
      follow-up. CONCLUSIONS: These positive results of intermediate measures suggest
      that, in Asian communities, screening mammography could be an important modality
      for detecting early stage breast carcinoma. However, the low compliance rates
      suggest that health education efforts must focus on issues related to
      acceptability if such programs are to succeed.

PMID- 9554532
TI  - Primary heterologous carcinosarcoma (metaplastic carcinoma) of the urinary
      bladder: a clinicopathologic, immunohistochemical, and ultrastructural analysis
      of eight cases and a review of the literature.
AB  - BACKGROUND: Heterologous carcinosarcomas of the urinary bladder are rare
      neoplasms, the histogenesis of which is still disputed. METHODS: The
      clinicopathologic, immunohistochemical, and ultrastructural features of eight
      cases were analyzed. RESULTS: The patients, 5 males and 3 females, had a median
      age of 70 years. Gross hematuria, dysuria, and urinary tract infections were the
      main presenting symptoms. Tumors were solitary in all cases and located in the
      right wall in six cases. Tumor size ranged from 2 to 12 cm (median, 5 cm). Four
      patients died of disease 2, 6, 17, and 42 months postoperatively, respectively.
      Microscopically, the tumors consisted mostly of a varied mixture of high grade
      transitional cell carcinoma with chondrosarcoma, osteosarcoma, rhabdomyosarcoma,
      and undifferentiated spindle cell (leiomyosarcoma-like) components with
      occasional transitional features between one component and another. All tumors
      but one invaded the muscularis propria or the perivesical fatty tissue.
      Immunohistochemically, keratin expression was observed focally in the sarcoma
      component as well as the carcinoma component. Reactivity for vimentin, desmin,
      muscle specific actin, and S-100 protein was observed in poorly differentiated
      areas in addition to the expected positivity of each histologic subtype of
      sarcoma. Ultrastructurally, one tumor showed evidence of both epithelial and
      chondrosarcomatous differentiation, whereas three contained rhabdomyosarcomatous
      elements. CONCLUSIONS: On the basis of the current series and a review of 55
      reports from the literature, primary heterologous carcinosarcoma of the urinary
      bladder proved to be a highly malignant type of neoplasm occurring predominantly
      in elderly males that was most often in an advanced stage at presentation and
      rapidly became lethal. Histogenetically, some heterologous carcinosarcomas should
      be regarded as a variant of sarcomatoid carcinoma (metaplastic carcinoma) that
      shows prominent heterologous differentiation.

PMID- 9554531
TI  - Neoadjuvant chemotherapy in the treatment of locally advanced cervical carcinoma
      in pregnancy: a report of two cases and review of issues specific to the
      management of cervical carcinoma in pregnancy including planned delay of therapy.
AB  - BACKGROUND: Women diagnosed with invasive cervical carcinoma during pregnancy are
      faced with difficult decisions regarding therapy and the fate of their unborn
      child. A modest treatment delay for International Federation of Gynecology and
      Obstetrics Stage I cervical lesions is considered acceptable in patients who wish
      to continue their pregnancy. METHODS: Two patients with locally advanced cervical
      carcinoma diagnosed early in the second trimester strongly desired continuation
      of their pregnancies. They were treated with neoadjuvant chemotherapy until the
      third trimester, and then underwent delivery and definitive surgical treatment.
      The patients were evaluated during pregnancy for evidence of a clinical response
      to chemotherapy. Intraoperative findings and pathologic analysis of the surgical
      material provided further objective data regarding disease status. RESULTS: Both
      patients experienced a dramatic reduction in tumor volume, rendering radical
      hysterectomy feasible at the time of cesarean section. In addition, both patients
      tolerated chemotherapy well and there were no adverse fetal effects. Favorable
      neonatal outcomes were achieved. One patient experienced recurrence within 5
      months of surgery, whereas the other patient remained without evidence of disease
      for 2 years. CONCLUSIONS: To the authors' knowledge, these reports constitute the
      first description of the use of neoadjuvant chemotherapy for invasive squamous
      cell carcinoma of the cervix in pregnancy (MEDLINE 1966-1997). This therapeutic
      option should be considered in selected women with locally advanced cervical
      carcinoma who do not want termination of their pregnancy.

PMID- 9554533
TI  - Mitosis identification in diffuse gliomas: implications for tumor grading.
AB  - BACKGROUND: The histologic differentiation of mitotic figures is a cornerstone of
      several highly predictive grading systems for gliomas. In some systems, the
      presence of even a single mitotic figure is sufficient to classify an astrocytoma
      as high grade. However, the extent of microscopic examination necessary to
      exclude the presence of significant mitotic activity has not been determined.
      METHODS: Hematoxylin and eosin-stained slides from 410 astrocytomas and 107
      oligodendrogliomas/oligoastrocytomas were reviewed until the first mitosis was
      identified or 100 400x fields had been reviewed without identification of a
      mitosis. The number of the field in which the first mitosis was found was
      correlated with diagnosis, grade, and survival. RESULTS: A review of 50 400x
      fields was necessary to achieve a >90% sensitivity in identifying a mitosis in a
      Grade 3 astrocytoma specimen, compared with 20 400x fields in anaplastic (Grade 3
      and 4) oligodendroglioma specimens. For Grade 3 astrocytomas, there was a
      significant independent correlation between survival and the field in which the
      first mitosis was found (P = 0.02). For the oligodendroglial tumors, there was a
      strong correlation between the number of fields counted until the first mitosis
      was found and grade (P < 0.0001). CONCLUSIONS: The evaluation of mitotic activity
      offers more prognostic information than can be obtained by the simple approach of
      noting only their presence or absence. Data were acquired regarding the diligence
      of the microscopic examination necessary to evaluate the presence or absence of
      mitotic activity. A 1 cm x 0.1 cm needle biopsy contains adequate tissue to
      evaluate mitotic activity for the purpose of histologic grading; however, this
      adequacy is dependent on the sample's being representative and composed entirely
      of cellular tumor.

PMID- 9554534
TI  - Nonnasopharyngeal lymphoepithelioma of the head and neck.
AB  - BACKGROUND: Lymphoepithelioma (squamous cell carcinoma with associated lymphoid
      stroma) commonly occurs in the nasopharynx, rarely at other sites. As a result,
      the clinical course and optimal treatment of nonnasopharyngeal lymphoepithelioma
      of the head and neck have not been well described. This retrospective study was
      undertaken to analyze the clinical course of the disease in patients treated at a
      single institution and to formulate recommendations for treatment based on that
      experience as well as results reported in the literature. METHODS: Between 1950
      and 1994, 34 patients with nonnasopharyngeal lymphoepithelioma of the head and
      neck were treated at the University of Texas M. D. Anderson Cancer Center. The
      patients' medical records were reviewed and their pathologic specimens evaluated.
      The primary tumor sites were: oropharynx (24 patients), salivary gland (4),
      laryngohypopharynx (4), and the maxillary sinus/nasal cavity (2). Assessed in
      accordance with the 1992 American Joint Committee Against Cancer TNM staging
      system, T classifications were TX-2, T1-7, T2-8, T3-10, and T4-7, and N
      classifications were N0-8, N1-5, N2-15, and N3-6. Treatment consisted of
      radiotherapy for 24 patients, excisional biopsy of the primary tumor followed by
      radiotherapy for 7 patients, and surgery for 3 patients. Of the patients treated
      with radiotherapy, neck dissections were performed on only two, both of whom had
      persistent lymph node masses after completing radiotherapy. The median dose
      delivered to the primary tumor was 65 gray (Gy) (range, 46-78 Gy). The median
      fraction size was 2.1 Gy (range, 1.6-3.2 Gy). RESULTS: The 5-year actuarial
      disease specific survival and overall survival rates were 59% and 39%,
      respectively. The 5-year actuarial local control rate for all patients was 94%.
      For the irradiated patients, the 5-year regional control rates were 77% overall
      and 83% within the radiation field. The 5-year actuarial rate of distant
      metastasis for all patients was 30%. For patients who presented with and without
      regional adenopathy, the 5-year rates of distant metastasis were 36% and 12%,
      respectively (P = 0.27). CONCLUSIONS: Nonnasopharygeal lymphoepithelioma is a
      radiosensitive disease. High rates of locoregional tumor control were achieved
      with radiotherapy at all head and neck sites. The main cause of treatment failure
      was distant metastasis, which occurred more frequently in patients with lymph
      node involvement. Radiotherapy is appropriate initial locoregional therapy for
      patients with this disease. Surgery should be reserved for patients who have
      persistent disease after completing radiotherapy. Systemic therapy is a
      reasonable approach for patients who present with regional adenopathy because
      they have a relatively high rate of distant metastasis.

PMID- 9554535
TI  - Generation of a monoclonal antibody that inhibits the procoagulant activity of
      various cancer cell lines.
AB  - BACKGROUND: Tumor procoagulant is one of the factors responsible for disseminated
      intravascular coagulation and metastasis. The authors found procoagulant activity
      in LK52 human squamous cell carcinoma cells, which they designated cancer cell
      derived blood coagulating activity 1 (CCA-1). A monoclonal antibody (MoAb) was
      generated to characterize this CCA-1 procoagulant activity. To date, antibodies
      that show an inhibitory effect on procoagulant activity as well as high
      reactivity in cancer cells are well known for their tissue factor specificity.
      METHODS: Characterization of the procoagulant activity of CCA-1 was performed and
      an anti-CCA-1 MoAb, FS01, was generated. CCA-1 expression on the cancer cell
      surface was examined by flow cytometry. Procoagulant activity of various cancer
      cell lines and the inhibitory effect of the FS01 MoAb on this procoagulant
      activity was monitored by a clot timer. RESULTS: The enzymologic character
      differed from that of cancer procoagulant (CP). The FS01 MoAb inhibited the
      procoagulant activity of CCA-1, but did not inhibit that of tissue factor. A
      positive correlation was observed between the expression intensity of CCA-1 and
      the inhibitory effect of the FS01 MoAb on the procoagulant activity of cancer
      cell lines. Expression of CCA-1 was observed more frequently than that of tissue
      factor in human cancer cell lines. CONCLUSIONS: The FS01 MoAb generated in the
      current study is a new antibody that reacts with various cancer cell lines, but
      not with normal cells. FS01 inhibits cancer cell-derived procoagulant activity
      and does not react with tissue factor and CP. CCA-1, which is recognized by the
      FS01 MoAb, appears to play a major role in cancer cell-derived procoagulant
      activity.

PMID- 9554536
TI  - The cancer specific advance directive.
AB  - BACKGROUND: Advance directives are an important part of end of life care, but
      current advance directive documents do not address the specific issues facing
      cancer patients. The authors' purpose was: 1) to develop a cancer specific
      advance directive, 2) determine whether oncology outpatients find this directive
      more acceptable than a generic advance directive, and 3) describe oncology
      outpatient preferences for life-sustaining treatment. METHODS: A cancer specific
      advance directive ("The Cancer Living Will"; the full text of the updated version
      is available at the University of Toronto Joint Centre for Bioethics website
      [URL: www.utoronto.ca/jcb]) was developed in four steps: 1) literature search, 2)
      key informant interviews, 3) focus groups, and 4) evaluation of face and content
      validity. Subsequently, 91 volunteer oncology patients were given copies of the
      cancer specific advance directive and the generic advance directive ("The
      University of Toronto Centre for Bioethics Living Will") from which it was
      adapted. Acceptability of the advance directive was measured by determining the
      participants' preferred directive. Participants recorded their treatment
      preferences in both the cancer specific and generic advance directives. RESULTS:
      Of 60 patients who returned their questionnaires, 50 expressed a preference for
      the advance directive. Thirty-two patients (64%; 95% confidence interval (CI), 49
      77%) preferred the disease specific Cancer Living Will and 18 patients (36%; 95%
      CI, 23-51%) preferred the generic Centre for Bioethics Living Will. Most
      participants who preferred the Cancer Living Will did so because it was more
      specific and relevant to their situation. CONCLUSIONS: The authors have developed
      and evaluated a cancer specific advance directive that they believe can be
      recommended for clinical use with cancer patients.

PMID- 9554537
TI  - Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma: a
      phase II study by the Cancer and Leukemia Group B.
AB  - BACKGROUND: In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of
      patients with advanced, previously untreated mesothelioma, dihydro-5-azacytidine
      (DHAC) demonstrated a 17% response rate, including 1 complete response, with only
      mild myelosuppression. This Phase II study (CALGB 9031) was conducted to
      determine the effectiveness of and toxicities that would result from adding
      cisplatin to DHAC administered to the same patient population. METHODS: Thirty
      six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by
      continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated
      every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent
      cycles if toxicity was minimal. Therapy was continued until disease progression
      or excessive toxicity mandated discontinuation. RESULTS: Overall, 5 objective
      responses were observed in 29 evaluated patients (objective response rate, 17%).
      The median duration of response was 6.6 months. Median survival was 6.4 months,
      with a median time to clinical failure of 2.7 months. The major toxicity noted
      was significant chest/pericardial pain, as was observed with DHAC alone. There
      were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively.
      Significant leukopenia was observed in 29% of patients, but there were no
      neutropenic fevers. CONCLUSIONS: The addition of cisplatin to DHAC did not
      increase the response rate over that observed with DHAC alone in patients with
      mesothelioma; however, it did increase toxicity, especially leukopenia. This
      combination is not recommended for further studies involving mesothelioma
      patients.

PMID- 9554538
TI  - The role of glucagon administration in the diagnosis and treatment of patients
      with tumor hypoglycemia.
AB  - BACKGROUND: Tumor hypoglycemia can be recurrent and severe enough to interfere
      with definitive antineoplastic treatment. Therefore, rapid commencement of
      effective therapy is essential. This is best accomplished by identifying which of
      the hypoglycemic processes is involved, as treatments differ. Some patients
      present with hypoglycemia and liver metastases; among them, only a few develop
      hypoglycemia as a result of a failure of hepatic glucose production. Most develop
      hypoglycemia as a result of an insulin-mediated process--either the secretion of
      insulin by an islet-cell tumor or the secretion of insulin-like growth factor-II
      by an extrapancreatic tumor. Administration of glucagon can rapidly make the two
      groups distinguishable, thus allowing institution of therapy and prompt
      symptomatic control of hypoglycemia. METHODS: The charts of seven patients with
      tumor hypoglycemia and liver metastases who had a glucagon stimulation test
      (serial glucose measurements after a 1 mg infusion of glucagon) as part of the
      workup for hypoglycemia were retrospectively reviewed. Those patients whose test
      revealed a rise in serum glucose of >30 mg/ dL were subsequently treated as
      outpatients, with a continuous glucagon infusion delivered by a portable pump.
      RESULTS: Three patients had an insulinoma and four had non-islet cell tumor
      hypoglycemia (NICTH) due to hepatocellular carcinoma, colon carcinoma, meningeal
      sarcoma, and hemangiopericytoma, respectively. All of the patients had liver
      metastases. Evaluation of these patients included a glucagon stimulation test (1
      mg intravenous push), which quickly provided information about the mechanism of
      tumor hypoglycemia and the direction towards therapy. All patients with
      insulinoma responded to glucagon with a rise in blood serum glucose levels,
      indicating adequate glycogen stores. The four patients with NICTH had mixed
      responses: in two patients, the response suggested that hypoglycemia was due to
      an insulin-like tumor product; glucose levels did not rise in the other two
      cases, indicating that hypoglycemia was due to poor hepatic glycogen
      reserve/liver failure. In all cases, a glycemic response to glucagon predicted
      good response to long term treatment with glucagon (0.06-0.3 mg/hour, via
      intravenous infusion pump). CONCLUSIONS: The glucagon stimulation test is a
      simple and fast approach that serves to clarify the etiology of hypoglycemia
      (diagnostic use) and guide effective long term strategies for its control
      (therapeutic use) in patients with neoplastic diseases and liver metastases.

PMID- 9554539
TI  - Neuroblastoma screening in the United States: results of the Texas Outreach
      Program for neuroblastoma screening.
AB  - BACKGROUND: Mass screening of infants for neuroblastoma began in Japan after
      studies suggested that survival rates could be improved by early detection. This
      study was initiated in 1991 to test the methodology and feasibility of screening
      for neuroblastoma within the U. S. health care system. METHODS: Infants ages 5-10
      months (mean age, 9 months, 25 days) who were born in Texas were screened for
      neuroblastoma. An enzyme-linked immunoadsorbent assay (ELISA) for homovanillic
      acid (HVA) and vanillylmandelic acid (VMA) used to quantify the HVA and VMA was
      performed on urine extracted from specimens dried on filter paper. Infants were
      recruited to participate in the study by several methods, and the effectiveness
      of each method was determined by calculating compliance rates. RESULTS: Between
      February 1991 and June 1994 a total of 14,046 infants were recruited to
      participate in neuroblastoma screening. Neuroblastoma was detected in 2 children
      for an incidence rate of 1 in 7023. A total of 291,158 screening kits were
      distributed to the parents of these infants, resulting in an overall compliance
      rate of only 4.8%. Compliance rates varied by method of distribution of the test
      kits: Houston Women, Infants, and Children (WIC) clinic (53%), volunteers (31%),
      Rio Grande Valley WIC clinics (14.5%), the patient's private physician (9.9%),
      and by mail (4.7%). CONCLUSIONS: Early detection of neuroblastoma in infants ages
      5-10 months was achieved using ELISA. Compliance rates were poor, but clinics
      with a preventive health focus, such as the WIC clinics, achieved higher
      compliance rates than did private physicians.

PMID- 9554541
TI  - Understanding and affirming the sexual/relationship realities of end-stage renal
      disease patients and their significant others.
AB  - End-stage renal disease (ESRD) frequently occurs within the social context of
      relationships and has many predictable consequences in the experience of patients
      and their significant others. Relationship and sexual issues and concerns must be
      assessed early in the treatment process and be continually attended to as
      patients seek new levels of coping. Sex-role conflicts, changes in sexual
      functioning and sexual self-esteem, challenges to both physical and emotional
      intimacy, and the life-altering consequences of chronic illness are all very real
      for ESRD patients. If a holistic perspective on the health care needs of ESRD
      patients is to be a reality, it will contain a concern for, active attention to,
      and involvement in the relationship/sexual dimension of life.

PMID- 9554540
TI  - Neurodevelopmental anomalies in children with neuroblastoma.
AB  - BACKGROUND: Case reports have associated neuroblastoma, a cancer derived from the
      embryonal neural crest, with aganglionosis coli and neurofibromatosis type I. The
      aim of the current study was to test the hypothesis that neuroblastoma is part of
      a global defect in neurodevelopment. METHODS: Neuropathologic findings from
      autopsies of children who died of neuroblastoma during the period 1980-1995 at
      the Children's Hospital of Pittsburgh were reviewed for macroscopic and
      microscopic abnormalities. As controls, autopsies of children who had died of
      other primary extracranial cancers over the same time period also were studied.
      Medical records of neuroblastoma patients for whom autopsies were available were
      reviewed for clinical evidence of preexisting nonmalignant neurologic disease.
      RESULTS: Of 145 children diagnosed with neuroblastoma, 49 had died, and autopsies
      not restricting examination of the brain had been performed on 13. Macroscopic
      anatomic abnormalities (a small cerebellum and the absence of the corpus
      callosum) were noted in one patient who was known to have been mentally retarded
      without having a defined syndrome. Microscopic abnormalities of cytoarchitecture
      were noted in that patient as well as 3 of the 12 other patients (focal cortical
      dysplasia [fcd], n = 3; leptomeningeal heterotopia, n = 1; abortive sulcation or
      flattened gyri, n = 2). None of 3 patients with only microscopic abnormalities
      had clinical evidence of problems with neurodevelopment. Of the 26 children with
      nonneuroblastoma cancers for whom complete autopsies were available, 1 infant had
      major macroscopic structural abnormalities of the brain. None of these patients
      had microscopic abnormalities (P < 0.01). CONCLUSIONS: Children with
      neuroblastoma have an increased incidence of abnormalities of brain
      cytoarchitecture, particularly fcd. These abnormalities are generally
      asymptomatic and are diagnosed by histologic examination. Such abnormalities
      cannot be attributed to chemotherapy and are not observed in other children with
      non-central nervous system tumors. These findings are consistent with the concept
      that neuroblastoma may occur in the setting of a more global defect in
      neurodevelopment. A blinded review of larger numbers of cases will be needed to
      verify these data.

PMID- 9554542
TI  - Kidney transplants from living donors: how donation affects family dynamics.
AB  - Living donors continue to provide the optimum outcome for kidney transplant
      recipients, yet information is limited on how donation can affect the donor and
      his or her family. Questionnaires returned by 524 donors whose donor
      nephrectomies took place between August 1, 1985 and December 31, 1996 at the
      University of Minnesota were analyzed to determine if perioperative complications
      influence their quality of life, among other emotional and lifestyle areas.
      Results showed that donors have a higher quality of life than the general
      population, confirming they have an increased self-worth and positive self
      esteem. An overwhelming 96% would donate again. However, donation was self
      reported as more stressful when complications were experienced (P = .003) and
      when donors were female (P = .041). Relatives other than immediate family members
      (extended relatives) were more likely to be among the 4% who said they would not
      donate again. Available support, financial impact, and relationship changes as a
      result of donation also were revealed. Relevant results from this larger study
      are discussed as they relate to how the renal donor and transplant family are
      affected.

PMID- 9554543
TI  - Family caregivers: caring for aging end-stage renal disease partners.
AB  - With the rapid aging of end-stage renal disease patients have come increasing
      burdens on families to provide care and support. This article focuses on the role
      changes, strains, and burdens for family caregivers, particularly spouses.
      Analysis is on the process of dramatic role changes and losses that occur within
      families and the resulting risks to dialysis patients and caregivers. Importance
      of constant assessment of caregivers by renal professionals is emphasized.
      Suggestions for families and professionals coping with role change and care
      burdens are offered. Concern is raised about American society shifting more care
      burdens onto families at a time of cultural change and stress on families,
      without enough societal support and programs to assist families adequately with
      care burdens of aging members.

PMID- 9554544
TI  - Advance directives in end-stage renal disease inherently involve family and
      staff.
AB  - Advance directives (ADs) have a pivotal role in the practice of clinical
      nephrology. The following discussion reviews our own viewpoint, drawing on the
      present literature and on many case anecdotes from our own practice. The review
      focuses on (1) the intrinsic value of ADs; (2) the impact of family and staff on
      clinical outcome in general; (3) family relationships and medical decision
      making, especially in the area of ADs; (4) the importance of communication within
      families and between families and staff, as characterized in "family meetings";
      and (5) the power of reconciliation when family members and staff "let go." In
      the final analysis, ADs present the opportunity for approaching medical decision
      making in a manner that can lessen the stress of making difficult decisions for
      the patient and even promote peace of mind for all concerned family and staff.

PMID- 9554545
TI  - Adolescent issues in renal treatment.
AB  - Everyone who helps to care for a growing and developing child has the potential
      to impact the future. Families provide the greatest influence and bear the major
      responsibility, but physicians, nurses, dietitians, social workers, teachers,
      camp counselors, and others who work with children make a direct contribution
      toward the development of the child's self image and image of the world around
      them. At no other time in an individual's life do other people have such awesome
      power and responsibility. Families and caregivers working together on behalf of a
      child may be likened to an extended family; their combined efforts are needed to
      help promote the resilience that children need to cope with serious chronic
      illness.

PMID- 9554546
TI  - Cultural basics and chronic illness.
AB  - Cultural factors have significant impact on the clinical encounter between health
      care professionals and their patient-families. A good continuing relationship is
      essential for successful management of chronic disease. Misunderstandings
      predicated on implicit cultural assumptions are a frequent potential hazard. This
      review outlines some possible problems and concludes by making eight suggestions
      for culturally sensitive and medically effective communication.

PMID- 9554547
TI  - A team's three-dimensional approach to assisting the end-stage renal disease
      family.
AB  - This review will identify ways in which the interdisciplinary team assists a
      family confronting end-stage renal disease (ESRD) for the first time. The
      developmental models of the family life cycle and the ESRD life cycle are used to
      understand the family's needs. The treatment team uses a three-dimensional
      approach of education, support, and communication to enhance family coping.

PMID- 9554548
TI  - Drug dosing in acute renal failure: the role of renal replacement therapy in
      altering drug pharmacokinetics.
AB  - The combination of multiple medical problems requiring complex drug therapy with
      rapidly changing organ functions that lead to pharmacokinetic alterations makes
      drug regimen design in the intensive care unit challenging. Acute renal failure
      leads to even greater physiologic disturbances requiring additional
      pharmacologic, nutritional, and dialytic support. A variety of renal replacement
      modalities, both intermittent and continuous, are used to manage the solute,
      volume, and acid-base derangements of patients with acute renal failure. Renal
      replacement therapies differ in their impact on drug dosing. The clinician must
      consider the impact of both disease and treatment if drug prescribing is to be
      optimal. Principles of solute removal are reviewed and concepts of drug regimen
      design are discussed. A practical approach to drug prescribing in this setting is
      described. Examples of dose adjustments for intermittent and continuous renal
      replacement therapies are provided.

PMID- 9554549
TI  - Dialysis through a child's eye.

PMID- 9554550
TI  - APO B 3' HVR polymorphism in healthy population: relationships to serum lipid
      levels.
AB  - We have analyzed allele frequency distribution at the hypervariable locus 3' to
      the apolipoprotein B gene in a healthy population sample (241 women and 246 men)
      from the Belgrade area. The bimodal distribution of sixteen different
      hypervariable region (HVR) alleles and the heterozygosity index (average 0.76) in
      both samples are similar to ones reported for other Caucasian populations.
      However, we found the hypervariable element containing 34 repeats-HVE34 allele to
      be the most common one in both female and male samples, and that there was a
      lower frequency of the HVE>36 alleles. For further analysis of 3'HVR allele
      frequency and its possible association with serum lipid levels, all HVR alleles
      were grouped into five main types (HVE<32, HVE32, HVE34, HVE36, and HVE>36), and
      the samples were divided into lipid quartiles. We found that (1) apo B gene 3'HVR
      polymorphism is associated with variation of normal lipid levels in males, (2)
      HVE32 alleles are associated with decreased serum levels of total cholesterol,
      LDL cholesterol, and triglycerides, and (3) HVR genotypes containing HVE34 and
      HVE36 alleles are associated with elevated serum levels of total cholesterol, low
      density lipoprotein (LDL) cholesterol, and triglycerides.

PMID- 9554551
TI  - Relative predispositional effects and mode of inheritance of HLA-DRB1 alleles
      among community-based Caucasian females with rheumatoid arthritis.
AB  - Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions
      70-74 are associated with susceptibility to rheumatoid arthritis (RA). However,
      the nature of the association and the mode of inheritance differ depending upon
      the source of RA patients and laboratory methodology. We studied the relative
      predispositional effects (RPE) and mode of inheritance of DRB1 alleles among a
      community-based sample of 180 RA patients and 116 healthy controls, all Caucasian
      females. Polymerase chain reaction (PCR)-based assays were used for DRB1
      genotyping, and the genotypic distributions were analyzed by both the RPE and
      antigen genotype frequency among patients (AGFAP) methods. We examined the
      evidence of synergy among DRB1 alleles for RA risk by comparing the observed DRB1
      genotype distribution to that predicted under Hardy-Weinberg equilibrium. Fifty
      six percent of RA cases were attributable to DRB1 alleles encoding the SE. The
      RPEs of DRB1 alleles were *0401 > *0404 > *1001 > *0408 > *0101. The strength of
      the RA association was not significantly different for these alleles. The AGFAP
      analysis was consistent with a recessive mode of inheritance for DRB alleles,
      while an additive (dominant) model was rejected. We found no evidence of synergy
      for RA risk among individual DRB1 alleles based on comparison of the observed vs.
      predicted genotype distributions. These results suggest that among community
      based Caucasian females with RA, the DRB1 RA susceptibility gene influences
      disease risk in a recessive fashion without synergy among individual DRB1
      alleles.

PMID- 9554552
TI  - Genotypic relative risks under ordered restriction.
AB  - In mapping diseases of complex aetiology, conventional linkage approaches narrow
      the location of the disease susceptibility locus to quite a large region so that
      candidate gene association studies are then necessary to further isolate these
      genes. However, even in the simplest scenario where the candidate locus is bi
      allelic, two statistical tests with various correcting factors have been
      proposed: a chi-square 1 df test (counting chromosomes) which may be slightly
      conservative and a 2 df chi-square test (counting genotypes) which may lack power
      because of the extra degree of freedom. This paper introduces a better and more
      powerful alternative which turns out to be a compromise between the two existing
      statistical tests. The asymptotic distribution of this test statistic is
      determined and the efficacy of the 3 tests are compared under different genetic
      models by simulation.

PMID- 9554553
TI  - Modeling hazard functions in families.
AB  - A genetic frailty model is presented for censored age of onset data in nuclear
      families where individuals carrying a genetic susceptibility gene have an
      increased risk of becoming affected. We use maximum likelihood via the EM
      algorithm to estimate the genetic relative risk and the allele frequency under a
      dominant susceptibility type and a proportional hazards model. When sampling is
      from a disease registry, likelihood corrections are necessary for reducing bias
      in the parameter estimates. In these biased samples, the full conditional
      likelihood is approximated by a likelihood conditional on the proband's age of
      onset. For unbiased samples, simulations show the distributions of the estimates
      are similar under both a semiparametric and the correctly specified parametric
      likelihoods. For biased samples, simulations under the approximate conditional
      likelihood show the median estimates of the allele frequency and genetic relative
      risk tend to under- and overestimate, respectively, the true values; however, the
      approximation is better for rarer allele frequencies (0.0033 vs. 0.01). In
      practice, large samples or more complex ascertainment corrections are
      recommended. Using the approximate conditional likelihood on familial breast
      cancer onset data collected as part of a case-control study at the Fred
      Hutchinson Cancer Research Center in Seattle, Washington, we estimate an allele
      frequency of 0.0009 (approximate 95% CI 0.0006-0.002) and a genetic relative risk
      of 104 (approximate 95% CI 55-181).

PMID- 9554554
TI  - Logistic regression model for analyzing extended haplotype data.
AB  - Recently, there has been increased interest in evaluating extended haplotypes in
      p53 as risk factors for cancer. An allele-specific polymerase chain reaction
      (PCR) method, confirmed by restriction analysis, has been used to determine
      absolute extended haplotypes in diploid genomes. We describe statistical analyses
      for comparing cases and controls, or comparing different ethnic groups with
      respect to haplotypes composed of several biallelic loci, especially in the
      presence of other covariates. Tests based on cross-tabulating all possible
      genotypes by disease state can have limited power due to the large number of
      possible genotypes. Tests based simply on cross-tabulating all possible
      haplotypes by disease state cannot be extended to account for other variables
      measured on the individual. We propose imposing an assumption of additivity upon
      the haplotype-based analysis. This yields a logistic regression in which the
      outcome is case or control, and the predictor variables include the number of
      copies (0, 1, or 2) of each haplotype, as well as other explanatory variables. In
      a case-control study, the model can be constructed so that each coefficient gives
      the log odds ratio for disease for an individual with a single copy of the
      suspect haplotype and another copy of the most common haplotype, relative to an
      individual with two copies of the most common haplotype. We illustrate the method
      with published data on p53 and breast cancer. The method can also be applied to
      any polymorphic system, whether multiple alleles at a single locus or multiple
      haplotypes over several loci.

PMID- 9554555
TI  - Using family history information to distinguish true and false positive model
      free linkage results.
AB  - Genome scans that test for increased marker identity-by-descent sharing between
      pairs of affected siblings have become increasingly common. These methods do not
      specify a priori a genetic model for the disease locus and as such lose the
      ability to specify the parental source of the disease allele. We propose a method
      that uses family history information to build a more complete model of disease
      and marker inheritance, while still avoiding specification of the parameters of
      the disease model of inheritance. One important use for such a model is to test
      whether a positive linkage result obtained during the course of a genome scan is
      a true or false positive result. The key to the new test statistics is the
      interaction between gender-specific marker identity-by-descent sharing and gender
      specific family history of disease. The method is useful when the disease locus
      of interest has a dominant mode of inheritance and a sufficient number of parents
      are genotyped at the marker locus. If these conditions are met, the proposed
      tests have good power to differentiate between true and false positive linkage
      results.

PMID- 9554556
TI  - Using information from both parents when testing for association between marker
      and disease loci.
AB  - Several extensions of the transmission/disequilibrium test (TDT) to multi-allelic
      markers now exist. In some of these, however, separate tests must be performed on
      male and female parents because of the non-independence of parental transmission
      patterns, reducing power, and complicating interpretation of the test results.
      Here we show that this non-independence is asymptotically irrelevant when using
      the allelic TDT of Bickeboller and Clerget-Darpoux [(1995) Genet Epidemiol 12:577
      582], allowing the analysis of data from both parents simultaneously.

PMID- 9554557
TI  - Analysis of Swedish male breast cancer family data: a simple way to incorporate a
      common sibling effect.
AB  - Based on a population-based cohort study, Olsson et al. [1993] found significant
      evidence for elevated incidence of breast and ovarian cancers among female first
      degree relatives of men with breast cancer. Using an extension of logistic
      regressive models we investigate whether, after allowing for multifactorial
      familial correlations, single locus segregation could be the cause of the
      elevated incidence in these families. The logit for a given sib in the class D
      logistic regressive model depends on the order in which affected sibs occur in a
      sibship. That makes the model less appropriate for the situation where a
      polygenic component or a common sibling environment may be present, as well as
      being computationally cumbersome. In this paper, we propose to use the proportion
      of siblings in a sibship who are affected to quantify a sibling correlation. That
      not only relaxes the interchangeability problem but also makes the model
      computationally efficient. We then use this modified class D logistic regressive
      model for our segregation analysis. Using the proportion of siblings in a sibship
      who are affected as a covariate resulted in a significantly higher likelihoods in
      all the models we investigated. We found evidence for a dominant Mendelian gene
      leading to early age of onset of breast and/or ovarian cancer. This could either
      be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.

PMID- 9554558
TI  - Laudatio Joel D. Kopple.

PMID- 9554559
TI  - Mechanisms of insulin-like growth factor-I-induced accelerated recovery in
      experimental ischemic acute renal failure.
AB  - Exogenous administration of recombinant human insulin-like growth factor I (rhIGF
      I) to normal rats or humans increases renal blood flow and glomerular filtration
      rate (GFR). In rats with ischemic acute renal failure (iARF) the peptide
      accelerates the recovery of renal function and tubular integrity. These latter
      effects may be caused by renal hemodynamic actions of IGF-I or may result from
      direct actions of IGF-I on injured tubular cells. To examine this hypothesis, in
      vivo studies were performed in rats with iARF and in vitro experiments were
      conducted using a model of anoxia/reoxygenation injury in primary cultures of rat
      proximal tubular cells. In rats with iARF, IGF-I ameliorates the rise in serum
      creatinine, improves GFR, increases the rate of bromodeoxyuridine (BrdU)
      incorporation and the mitosis score, and reduces the number of apoptotic bodies.
      In acutely injured proximal tubular cells, IGF-I receptor mRNA levels decrease,
      but the remaining receptors are functional as indicated by ligand-induced
      phosphorylation of the IGF-I receptor beta-subunit. In anoxia/reoxygenation
      injured cells, exogenous rhIGF-I improves ATP repletion, increases 3H-thymidine
      and BrdU incorporation and reduces the incidence of apoptosis as determined by
      the TUNEL method. We conclude that rhIGF-I accelerates the recovery of renal
      function in rats with iARF probably through hemodynamic effects, but in addition
      through direct metabolic, mitogenic and antiapoptotic actions on injured tubules.

PMID- 9554560
TI  - Fat-soluble vitamins in patients with acute renal failure.
AB  - OBJECTIVE: Systematic investigations on the status of fat-soluble vitamins in
      patients with acute renal failure (ARF) are lacking and hence no recommendations
      for vitamin supply can be defined for these subjects. Thus we compared the status
      of fat-soluble vitamins, of transport molecules and some vitamin-dependent
      proteins in patients with ARF and healthy controls. SETTING: Nephrology unit of a
      university hospital. PATIENTS AND METHODS: Eight patients with ARF requiring
      hemodialysis therapy were investigated and 28 healthy volunteers served as
      controls. Plasma concentrations of retinol (vitamin A) and retinol-binding
      protein (RBP), 25-OH and 1,25-(OH)2 vitamin D3, of parathyroid hormone (PTH), of
      alpha-tocopherol (vitamin E) and of phylloquinone (vitamin K), osteocalcin and
      noncarboxylated osteocalcin, respectively, were measured and plasma lipoprotein
      fractions (as vitamin transport vehicle) were evaluated. RESULTS: Vitamin A
      levels were decreased (p < 0.001), but RBP levels were normal in ARF patients.
      Vitamin D3 metabolites 25-OH and 1,25-(OH)2 vitamin D3 plasma levels were
      profoundly depressed, and PTH was elevated (p < 0.001). Vitamin E plasma
      concentration was reduced (p < 0.001) but this cannot be accounted for by
      decreased LDL cholesterol or triglyceride levels. In contrast, vitamin K plasma
      level was rather elevated in ARF patients with a broad range of individual
      values. Blood coagulation was normal but total and carboxylated osteocalcin were
      decreased. No correlation of vitamin K concentrations and any of the plasma
      lipoprotein fractions could be identified. CONCLUSION: With the exception of
      vitamin K, profound deficiencies of fat-soluble vitamins develop in patients with
      ARF. Current recommendations for vitamin supplementation are inadequate and
      should be reevaluated for these patients.

PMID- 9554561
TI  - Osteopontin expression in the kidney during unilateral ureteral obstruction.
AB  - Osteopontin is a bone protein also expressed in other tissues. Increased
      osteopontin is thought to be associated with tissue inflammation. We used
      immunocytochemical analyses and polymerase chain reaction amplification of mRNA
      to examine osteopontin expression and regulation in unilateral ureteral
      obstruction (UUO) in rats, a model of inflammatory kidney disease. In the
      obstructed kidney, osteopontin mRNA and protein were significantly increased. The
      increase reached 4-fold after 1 day of UUO and persisted at this level for the 5
      day duration of UUO. Immunocytochemical analyses showed increased osteopontin
      protein in tubular cells of the obstructed kidney cortex from days 1 through 5 of
      UUO. No such significant increase was apparent in the glomerulus or interstitium.
      Increased osteopontin mRNA and protein likewise occurred in the tubular cells of
      the obstructed kidney of rats that had undergone whole-body irradiation to
      eliminate macrophage infiltration into the experimental kidney. Purified
      osteopontin was found to be a chemoattractant for macrophages isolated from the
      rat peritoneum. Enalapril treatment, which decreases macrophage infiltration of
      the obstructed kidney, had no effect on the increase in osteopontin mRNA but
      significantly attenuated the increase in protein in tubular cells. Western blot
      analysis of whole cortical homogenates revealed that the osteopontin antibody
      recognized one protein of 67 kD. The amount of this protein was substantially
      decreased in kidney homogenates obtained from enalapril-treated compared to
      untreated animals. Increased osteopontin synthesis may, therefore, contribute in
      part to the inflammatory response that characterizes obstructive nephropathy.

PMID- 9554562
TI  - High-protein diets augment albuminuria in rats with Heymann nephritis by
      angiotensin II-dependent and -independent mechanisms.
AB  - Urinary albumin excretion (U(alb)V) increases following dietary protein
      augmentation (DPA) in nephrotic humans and rats. Angiotensin-converting enzyme
      inhibitors (ACEI) blunt, but do not entirely prevent, increased U(alb)V at doses
      that reduce blood pressure and entirely block the pressor effect of exogenously
      administered angiotensin I (Ang-I), suggesting that angiotensin II (Ang-II) might
      not mediate the effect of DPA on U(alb)V. We determined the effect of losartan
      (Los), a specific Ang-II receptor antagonist, and compared its effect to that of
      enalapril (En), an ACEI, on DPA-induced increase in U(alb)V in rats with passive
      Heymann nephritis (HN). When Los was administered to HN rats for 48 h prior to
      DPA from 8.5 to 40% casein. U(alb)V increased in an identical fashion in treated
      and untreated rats, even though Los caused hypotension and prevented the pressor
      effect of infused Ang-II. Only on day 6 after DPA did U(alb)V decrease. We then
      measured the effect of duration of pretreatment with Los on Ang-II binding to
      isolated glomeruli. Maximal inhibition of Ang-II binding required treatment with
      Los for 6 days. We then pretreated HN rats with either En or Los for 6 days prior
      to DPA. In contrast to administration of Los for 2 days prior to DPA,
      pretreatment with either Los or En for 6 days entirely prevented any increase in
      U(alb)V. We then increased dietary NaCl from 0.2% to 2% (HS) to determine whether
      En or Los would modulate U(alb)V after DPA when Ang-II activity was suppressed.
      En reduced the DPA-mediated increase in U(alb)V regardless of dietary NaCl, while
      Los was effective only in when dietary NaCl was reduced (0.2%), suggesting that
      under these conditions ACEI reduces U(alb)V by a mechanism that is independent of
      inhibition of Ang-II and that high protein diets augment U(alb)V by both Ang-II
      independent and Ang-II-dependent mechanisms.

PMID- 9554563
TI  - Corticomedullary procollagen alpha1(IV) mRNA levels and localization after
      subtotal nephrectomy.
AB  - The relationships between tubular hypertrophy/hyperplasia, procollagen alpha1(IV)
      mRNA levels, and the development of tubular basement membrane thickening were
      studied in male Sprague-Dawley rats subjected to subtotal renal ablation and
      sacrificed 2 or 15 days later. Tubular hypertrophy and hyperplasia were
      demonstrable at 2 days, however no increment in procollagen alpha1 (IV) mRNA
      levels was discerned at that time, demonstrating a dissociation between mRNA
      levels for classical type IV collagen and tubular enlargement. At 15 days,
      tubular procollagen alpha1(IV) mRNA levels did increase approximately 2-fold (p <
      0.002), localizing predominantly in proximal tubules in the deep cortex and outer
      medullary stripe. At this time point, there was still no significant correlation
      to tubular enlargement, but there was a significant correlation to tubular
      basement membrane thickening (r = 0.89, p < 0.01). These studies demonstrated
      that an increase in mRNA for classical type IV collagen is not required for the
      development of hypertrophy, and that the increment is a better marker for matrix
      expansion than it is for hypertrophy.

PMID- 9554564
TI  - High-glucose media enhance the responsiveness of tubular cells to growth
      promoters: effect on lysosomal cathepsins and protein degradation.
AB  - Nephromegaly is a prominent feature of diabetic nephropathy and predominantly
      reflects increased renal tubule mass, mostly due to hypertrophy. To elucidate
      pathogenetic factors involved, we studied the effects of high glucose (HG) alone,
      and in combination with hormones/growth promoters: angiotensin II (10(-7) M);
      parathyroid hormone (10(-7) M); insulin-like growth factor-1 (10(-7) M), or
      transforming growth factor-beta1 (TGF-beta1, 10 ng/ml) in a renal cell line (LLC
      PK1) with many characteristics of the proximal tubule. Activities of lysosomal
      cathepsins (B, L+B and H) and the protein turnover were investigated. Exposure to
      HG (25 mM) for up to 48 h increased cellular protein content, due to enhanced
      protein synthesis, while protein degradation rate and cathepsin activities tended
      to lower values. Hyperosmotic mechanisms of glucose action were excluded, since
      these effects were not induced by mannitol. In normoglycemic conditions only TGF
      beta1 decreased cathepsin activities and protein degradation rate significantly.
      However, in HG media all applied hormones/growth factors significantly lowered
      the protein degradation rate, as well as lysosomal cathepsin activities. The
      enhanced responsiveness could contribute to the impaired protein turnover, with
      consequent hypertrophy of the tubulointerstitium in diabetic nephropathy.

PMID- 9554565
TI  - Inhibition of protein synthesis by acid in L6 skeletal muscle cells: analogies
      with the acute starvation response.
AB  - Impaired protein synthesis (PS) occurs in skeletal muscle during acute
      starvation. Even though it is well established that uraemic metabolic acidosis
      (MA) stimulates protein degradation (PD) and is a major contributor to skeletal
      muscle wasting in chronic renal failure, the accompanying effects of MA on PS are
      much less clear. Previous work has shown that, in cultured L6 skeletal muscle
      cells, PD and leucine oxidation are stimulated by acid. The aim of the present
      study was to determine whether acid (like acute starvation) can also inhibit PS.
      PS (14C-phenylalanine incorporation) was measured in L6 cells in MEM + 2% serum
      at acid pH (7.1) or control pH (7.5). After 24 h, acid inhibited PS (7.7 +/- 0.2
      vs. 8.9 +/- 0.1 nmol Phe/4 h/35-mm culture well in controls, p = 0.01) and this
      was maintained at 72 h. In vitro this could arise because acid only inhibits the
      rapid PS occurring in dividing cells. However, when division was abolished with
      10(-5) mol/l cytosine arabinoside, PS inhibition by acid still occurred (6.9 +/-
      0.1 vs. 8.3 +/- 0.2 at control pH, p < 0.05). Acid also had no effect on the
      specific radioactivity of cellular phenylalanine, suggesting that the impaired PS
      was not a consequence of inadequate labelling of this pool. Elevated PD and
      impaired PS together led to loss of 7% of the total protein in only 28 h (-21 +/-
      3 microg/well, p = 0.004). This combination of impaired PS with increased PD and
      increased leucine oxidation in response to acid resembles the response of
      skeletal muscle to acute starvation. These superficial similarities between the
      starvation state and MA suggest that fundamental metabolic signals may occur
      which are common to both states.

PMID- 9554566
TI  - Relationship between whole-body protein turnover and serum creatinine in
      chronically uremic patients.
AB  - To investigate the relationship between decline in renal function and alterations
      of protein metabolism we determined the rate of whole-body protein turnover in a
      group of 15 postabsorptive chronically uremic patients (9 males and 6 females)
      with different levels of serum creatinine concentrations (average 5.7 +/- 0.4
      (SE) mg x dl(-1); range 3.3-9.1). Patients' age and body mass index were 53 +/- 4
      years (range 26-73) and 24.7 +/- 0.6 kg/m2 (range 20.3-28.7), respectively.
      Nutritional status (plasma albumin 3.6 +/- 0.4 g x dl[-1]) and acid-base
      equilibrium (arterial pH 7.38 +/- 0.01) were fairly controlled by therapy. Whole
      body leucine rate of appearance (Ra), an index of whole-body protein turnover,
      was assessed using a stable isotope technique. L-[1-(13)C]leucine was
      continuously infused and plasma [1-(13)C]alpha-ketoisocaproic acid enrichment was
      determined in steady-state conditions as a marker of the intracellular leucine
      enrichment. The average leucine Rawas 2.03 +/- 0.13 micromol x kg(-1) x min(-1)
      (range 1.29-3.19). Using simple linear regression analysis, the coefficient of
      correlation between the individual values of serum creatinine concentration and
      leucine Ra was 0.59 (n = 15; p = 0.02). Leucine Ra did not significantly
      correlate with blood pH or plasma albumin. In conclusion, we found a positive
      linear relationship between the values of plasma creatinine concentration and the
      rate of whole-body protein degradation. This correlation suggests that the
      progression of renal insufficiency is associated with accelerated rates of
      turnover of body proteins.

PMID- 9554567
TI  - Effects of recombinant growth factors on energy expenditure in maintenance
      hemodialysis patients.
AB  - We compared the metabolic effects of recombinant human (rh) insulin-like growth
      factor (IGF)-1 or a combination of rhIGF-1 + rh growth hormone (GH) on resting
      energy expenditure (REE) in 8 maintenance hemodialysis (MHD) patients. Seven
      males and 1 female (aged 41.6 +/- (SD) 12.4) with no evidence of malnutrition
      (BMI 21.6 +/- 2.2 kg/m2, serum albumin 45 +/- 2 g/l, serum IGF-1 359 +/- 165
      microg/l) received either rhIGF-1 (80 microg/kg/day) or rhIGF-1 (80
      microg/kg/day) + rhGH (50 microg/kg/day) for 3 days in a random crossover design.
      REE and the respiratory quotient (RQ) were measured at rest before and after the
      3-day treatment. The results confirmed that MHD patients have a REE not different
      from normal individuals. REE was strongly correlated with lean body mass but not
      with fat mass. rhIGF-1 treatment did not modify REE despite doubling serum IGF-1
      values, whereas a combined rhIGF1 + rhGH treatment significantly increased REE by
      11% (p < 0.001). There was no change in RQ under both treatments, in response to
      a proportionate increase in VCO2 and VO2. These results show that energy
      expenditure is mainly dependent upon lean body mass in well-nourished MHD
      patients. The metabolic effects of rhIGF-1 and rhGH on energy expenditure may
      differ in response to their opposite effects on lipid oxidation and insulin
      regulation.

PMID- 9554568
TI  - Effects of a meat meal on renal sodium handling and sodium balance.
AB  - Protein ingestion increases renal blood flow and glomerular filtration rate
      (GFR). This study investigated in healthy adults if the renal response to protein
      ingestion includes changes in urinary sodium (Na) excretion rate and Na balance.
      Renal clearance of Na and inulin (used as index of GFR) were measured in 25
      healthy adults before (90 min) and after (180 min) a standard meal and, as
      control, before and after administration of water and Na-chloride (saline). The
      meal consisted of red lean meat (2 g protein/kg body weight); in control
      experiments, water and Na were given to match water and Na content of the meal.
      ANOVA for repeated measures, Student's t-test, and linear regression were used
      for statistical analysis. GFR and urinary Na excretion increased over baseline
      after the meal (p < 0.001), not after saline. The post-meal natriuretic response
      was accounted for an early (0-90 min) increase in glomerular filtered load of Na
      (p < 0.001) and a late (90-180 min) reduction in tubular Na reabsorption (p <
      0.02). Urine flow rate and plasma Na did not significantly change after the meal
      and in control experiments. Analysis of Na balance showed that post-meal Na
      excretion was significantly higher than baseline also after Na balance returned
      to pre-meal values. In healthy individuals, a meat meal stimulates natriuresis
      and causes a net decrease in Na balance. The renal natriuretic response to the
      meal appears secondary to the meal-induced changes in renal hemodynamics. The
      data are in keeping with the hypothesis that dietary protein intake affects also
      renal Na handling.

PMID- 9554569
TI  - Nutritional considerations in the treatment of patients with chronic uremia.
AB  - Low-protein diets ameliorate uremic symptoms and some of its metabolic
      complications. These diets can be used successfully to treat patients with
      chronic renal failure (CRF) because they are able to activate normal compensatory
      responses when protein intake is restricted and their protein and energy
      requirements are similar to healthy subjects. However, there has been concern
      that dietary therapy compromises the nutritional status of CRF patients and that
      initiating dialysis would be preferable to this type of therapy. Kopple and co
      workers have identified the requirements of CRF patients for protein and calories
      and available evidence indicates that when properly implemented, low-protein
      diets are safe and can maintain lean body mass even during long-term therapy.
      Based on the information published by Kopple and co-workers, the strategies for
      treating CRF patients should include careful analysis of the diet and the
      nutritional status of the patient.

PMID- 9554570
TI  - Intermittent calcitriol therapy and growth in children with chronic renal
      failure.
AB  - Intermittent calcitriol (1,25D) therapy has been used for the management of
      secondary hyperparathyroidism in children with chronic renal failure; however,
      the development of adynamic bone has been demonstrated in up to 40% of pediatric
      patients after 12 months of intermittent 1,25D therapy. To assess its effect on
      linear growth, we compared growth and biochemical data from 16 prepubertal
      patients with biopsy-proven secondary hyperparathyroidism during 12 months of
      intermittent 1,25D therapy and the preceding year of daily 1,25D therapy. While Z
      scores for height remained stable during daily therapy, values decreased from 
      1.8 +/- 0.32 to -2.0 +/- 0.33, p < 0.01, during intermittent 1,25D therapy; the
      largest reductions were seen in those who developed adynamic bone. Reductions in
      growth may be due to the direct inhibitory effects of large intermittent doses of
      calcitriol on chondrocyte activity.

PMID- 9554571
TI  - Salt intake and renal outcome in patients with progressive renal disease.
AB  - Experimental studies suggest that salt intake plays a critical role in the
      progressive glomerular filtration rate (GFR) loss of established renal disease;
      however, this issue has never been addressed in humans. To this aim, we have
      retrospectively analyzed the clinical data of patients with chronic renal failure
      (CRF), in whom a low-protein diet was prescribed, over a period of about 3 years.
      On the basis of the daily urinary sodium output, the patients were divided into
      two groups: a group of patients constantly ingesting > 200 mEq NaCl/day (high
      sodium intake, HSD, n = 30) and a group in which salt intake was < 100 mEq/day
      (low sodium intake, LSD, n = 27). Patients taking diuretics or ACE inhibitors
      were excluded. At baseline, the LSD group, as compared to the HSD group, was
      characterized by significantly lower creatinine clearance (24 +/- 2 vs. 28 +/- 2
      ml/min) and higher proteinuria (2.9 +/- 0.3 vs. 1.5 +/- 0.2 g/day). Despite the
      presence of these risk factors for progression, and a similar control of blood
      pressure (the average of the mean arterial pressure during follow-up was 111 +/-
      2 mm Hg in LSD and 107 +/- 2 mm Hg in HSD), the LSD patients showed a better
      renal outcome: in this group, as compared to HSD, the GFR decline was lower (0.25
      +/- 0.07 vs. 0.51 +/- 0.09 ml/min/month, p < 0.05), and proteinuria did not
      change while it markedly increased in HSD. During follow-up, LSD patients also
      ingested a significantly lower amount of protein. This study therefore suggests
      that efficacious salt restriction in CRF patients improves the outcome of renal
      disease independent from its antihypertensive effects.

PMID- 9554572
TI  - The suprachiasmatic nucleus: a 25-year retrospective.
AB  - The suprachiasmatic nuclei (SCN) of the anterior hypothalamus contain the master
      circadian pacemaker in mammals. On the occasion of the 25th anniversary of the
      discovery of the SCN as the circadian clock, Charles A. Czeisler and Steven M.
      Reppert organized a meeting to review milestones and recent developments in the
      study of the SCN. The discovery that the SCN contain tissue necessary for
      generation of circadian rhythmicity was established by lesion studies published
      in 1972. The second phase of study demonstrated unequivocally that the SCN
      contain an autonomous circadian pacemaker. The principal studies in this period
      showed the presence of metabolic and electrical activity rhythms in the SCN in
      vivo and progressed to studies showing that the SCN maintain rhythmicity in
      vitro, demonstrating that the transplanted SCN can restore circadian function
      following destruction of the host SCN and ultimately showing that single SCN
      "clock cells" exhibit independent rhythms in firing rate. The third phase of
      study, aimed at identifying the biochemical and molecular mechanisms responsible
      for rhythmicity within the SCN, has begun with the identification of circadian
      mutants (tau mutant hamsters and Clock mutant mice) and the isolation of the
      Clock gene. This report traces the important steps forward in our understanding
      of the suprachiasmatic circadian clock by recounting the information presented at
      the SCN Silver Anniversary Celebration.

PMID- 9554574
TI  - Circadian parameters as individual characteristics.
AB  - Human circadian rhythms that are free running in temporal isolation can show an
      extreme variability of the sleep-wake cycle without the subject being aware of
      it. This is due mainly to a systematic adjustment of certain circadian time
      structures to the varying length of the "day": the perception of long time
      intervals in the range of 1 h and the intervals between meals have a strong
      positive correlation with the duration of wake time alpha, in contrast to the
      amount of hourly locomotor activity that is negatively correlated with alpha. So
      far, the dependence of locomotor activity, of the "1-h" intervals, and of the
      intermeal intervals on alpha is well documented for the data sets of single
      subjects. The present article demonstrates that the correlations found
      intraindividually also apply if data from several subjects are compared. If
      plotted as a function of the mean individual alpha, the individual means of "1-h"
      intervals and of the intermeal intervals show the same positive correlation and
      the means of locomotor activity show the same negative correlation with alpha as
      known from single individuals. It is to be concluded that each individual has its
      characteristic place on the regression lines that describe the dependence of the
      three circadian parameters on the duration of wake time.

PMID- 9554573
TI  - A parallelism between human body temperature and performance independent of the
      endogenous circadian pacemaker.
AB  - A battery of performance tests involving manual dexterity, serial search, and
      verbal reasoning was given about seven times per day to 2 healthy young male
      subjects (22 and 25 years of age) involved in separate forced desynchrony
      studies, each involving several months of temporal isolation. In these studies,
      the period lengths (denoted T) of the imposed day lengths (sleep/wake and
      light/dark cycles) were 25.8 and 26.0 h for the 2 subjects. For each subject, the
      endogenous circadian pacemaker (ECP) failed to entrain to a period of T and
      instead free ran at a period length denoted tau (24.2 and 24.5 h). By educing
      performance rhythms (and rectal temperature rhythms) separately at tau and at T
      (after three complete beating cycles for the first subject and two complete
      beating cycles for the second subject), the hypothesis could be tested as to
      whether performance and temperature were parallel, both when educed at tau
      (indicating ECP influence) and when educed at T (indicating sleep/wake cycle
      influences). The hypothesis was consistently confirmed at tau and mostly
      confirmed at T. For most variables, when educed at T, both performance speed and
      body temperature showed an inverted V-shaped function, with a peak about 9 to 12
      h after waking.

PMID- 9554575
TI  - Testing the hypothesis of a circadian phase disturbance underlying depressive
      mood in nonseasonal depression.
AB  - In a crossover design, 8 nonseasonal depressed subjects, selected on the presence
      of diurnal mood variations, and 8 sex- and age-matched controls were exposed to
      dim light (< 10 lux) in the evening (18:00-21:00 h) and bright light (2500 lux)
      in the morning (ML, 6:00-9:00 h), to dim light in the morning and bright light in
      the evening (EL), or to dim light both in the evening and in the morning (DL)
      during 3 consecutive days in each of these conditions. There were no initial
      phase differences between depressed and healthy subjects in the timing of dim
      light melatonin onset, sleep termination, and body temperature. The phase shifts
      after EL and ML in both healthy and depressed subjects were as expected on the
      basis of a human phase response curve. On average, there was no therapeutic
      effect of the light exposure in the depressed patients. Two patients improved,
      but these effects do not seem to be related to shifts in the circadian system.

PMID- 9554576
TI  - Decreased light intensity alters the perception of day length by male European
      starlings (Sturnus vulgaris).
AB  - The breeding season of wild starlings is controlled by photoperiod. Full breeding
      condition is attained during exposure to lengthening days in the spring, and
      photorefractoriness ensues. The reproductive system of starlings will not
      subsequently be stimulated by long day lengths until photorefractoriness is
      dissipated by the short day lengths experienced in the autumn and winter. Unlike
      most studies on avian photoperiodism, this investigation involved manipulation of
      light intensity of a fixed photoperiod rather than of photoperiod itself.
      Photosensitive starlings transferred from short days to long days of different
      light intensities underwent graded reproductive responses according to the light
      intensity they experienced. Testes size in the group in the lowest intensity (3
      lux) increased faster than that in controls on short days of normal intensity,
      but they did not become photorefractory. Testes size increased in the groups on
      13, 45, and 108 lux and subsequently became photorefractory. However, the 13- and
      45-lux groups required more time to become photorefractory than did the 108-lux
      group. The responses observed were similar to those seen in starlings exposed to
      different photoperiods (e.g., 11 h light:13 h dark [11L:13D], 13L:11D, 16L:8D,
      18L:6D), even though all were on the same 18L:6D photoperiod. Initially, the
      results appear to challenge the external coincidence model for photoperiodic time
      measurement, but consideration of the phase response curve of the circadian
      rhythm of photoinducibility in starlings and the way in which it might be
      affected by low light intensities refute this challenge.

PMID- 9554577
TI  - Photoreception in entrainment of rhythms and photoperiodic regulation of diapause
      in a hemipteran, Graphosoma lineatum.
AB  - The role of compound eyes in photoperiodic regulation of diapause and entrainment
      of circadian rhythms was studied in a hemipteran, Graphosoma lineatum. Bilateral
      removal of compound eyes resulted in the loss of locomotor rhythmicity under both
      24-h light cycle and constant darkness. The arrhythmicity was associated with the
      loss of photoperiodic regulation of diapause. Females with removed compound eyes
      had similar incidence of oviposition under diapause preventing long-day
      photoperiod (light:dark [LD] 18:6) and diapause inducing short-day photoperiod
      (LD 12:12). By contrast, both locomotor rhythmicity and photoperiodic regulation
      of diapause were maintained after unilateral removal of compound eyes. The
      results suggest that the compound eye-optic lobe axis is involved in the
      transmission of light signals for both entrainment of rhythms in locomotor
      activity and photoperiodism. The compound eyes probably act as photoreceptors in
      both transmission chains. Sites of the clocks for the two phenomena are
      discussed.

PMID- 9554578
TI  - Molecular circadian oscillators: an alternative hypothesis.
AB  - Results from experiments in different organisms have shown that elements of input
      pathways can themselves be under circadian control and that outputs might feed
      back into the oscillator. In addition, it has become clear that there might be
      redundancies in the generation of circadian rhythmicity, even within single
      cells. In view of these results, it is worth reevaluating our current working
      hypotheses about the pacemaker's molecular mechanisms and the involvement of
      single autoregulatory genes. On one hand, redundancies in the generation of
      circadian rhythmicity might make the approach of defining a discrete circadian
      oscillator with the help of single gene mutations extremely difficult. On the
      other hand, many examples show that components of signal transduction pathways
      can indeed be encoded by single genes. The authors have constructed a model
      placing an autoregulatory gene and its products on an input pathway feeding into
      a separate oscillator. The behavior of this model can explain the majority of
      results of molecular circadian biology published to date. In addition, it shows
      that different qualities of the circadian system might be associated with
      different cellular functions that can exist independently and, only if put
      together, will lead to the known circadian phenotype.

PMID- 9554579
TI  - Hematoxylin procedure for staining mature pollen grains in maize with
      dimethylsulfoxide as a clearing agent.
AB  - Observing nuclei of mature pollen grains in maize is extremely difficult because
      the starch granules surrounding the nuclei are deeply stained. The cytoplasm of
      hematoxylin stained pollen grains becomes clear when DMSO and gentle heating are
      used. By separating the staining and clearing processes, uniformly stained pollen
      grains were consistently obtained. Using this method, 2,000 pollen grains were
      examined and it was determined that 99.5% were in the normal tricellular state,
      while pentacellular pollen, bicellular pollen and pollen grains with two
      vegetative nuclei were observed in the remaining 0.5%.

PMID- 9554580
TI  - Fluorescence in situ hybridization (FISH): DNA probe production and hybridization
      criteria.
AB  - We describe methods for the production of fluorescence in situ hybridization
      (FISH) probes and the utilization of these probes for the detection of
      complementary DNA sequences with accuracy and sensitivity for application in both
      basic research and clinical diagnosis. Due to the frequent use of FISH in many
      laboratories, it is important to apply the most convenient and reproducible
      approach. This review describes some of the most recent techniques, and includes
      versatile, effective and simple methods of probe production and fluorescence in
      situ hybridization. We also describe methods for the production of region
      specific and chromosome-specific DNA probes and hybridization techniques for the
      visualization of these probes.

PMID- 9554581
TI  - Histochemical determination of stereoselectivity of esterases in normal pancreas
      and pancreatic tubular adenocarcinoma of hamsters.
AB  - Esterases in normal hamster pancreas and pancreatic tubular adenocarcinoma of
      ductal origin induced by N-nitrosobis(2-oxopropyl)amine were stained in cryostat
      sections with mixtures of a diazonium salt (fast blue RR) and with each of the
      enantiomers of alpha-naphthyl N-methoxycarbonylalaninate, N
      methoxycarbonylvalinate, and N-acetylprolinate. Azo coupling of alpha-naphthol
      formed by enzymatic hydrolysis with the diazonium salt gives an azo dye that
      indicates the presence and amount of the enzyme activity in situ. Comparison
      between the color intensities obtained with each of the enantiomers of a chiral
      alpha-naphthyl ester shows the stereoselectivity, or enantiomeric preference, of
      the enzyme. Esterases in acinar cells of the normal pancreas showed slight
      stereoselectivity for N-methoxycarbonylalaninate, while esterases in fat cells
      scattered throughout the exocrine pancreas showed high stereoselectivity for (R)
      N-acetylprolinate. These esterase activities were not found in the tumor, but
      another prominent esterase activity with high stereoselectivity for (S)-N
      methoxycarbonylvalinate was found. Similar results were obtained by staining
      after polyacrylamide gel electrophoresis showing that the bands of esterases in
      the adenocarcinoma stained only with the S enantiomer of the N
      methoxycarbonylvalinate. The present method is a valuable tool for designing
      anticancer prodrugs that are activated by tumor-specific esterases.

PMID- 9554582
TI  - Cytological comparison of leaves and stems of Prunus avium L. shoots cultured on
      a solid medium with agar or gelrite.
AB  - An axillary proliferating clone of Prunus avium L. was subcultured every four
      weeks on solid MS medium with agar as the gelling agent. Vitrification
      (hyperhydricity) of shoots was induced in one four week cycle with the same
      medium except that agar was replaced by gelrite. During culture on the vitrifying
      medium, the water content of the shoots progressively increased with a parallel
      decrease in chlorophyll content. Cytological differences between the leaves and
      stems of the vitrified and normal shoots were detected by light and electron
      (both transmission and scanning) microscopy. Leaves of vitrified shoots were
      characterized by lower number of chloroplasts in the palisade parenchyma and by a
      defective cuticle. The stems of vitrified shoots had a less developed and
      lignifled xylem tissue, lacked sclerenchymatic areas and showed hypertrophy of
      the cortical parenchyma. More intense vacuolar activity with evaginations of the
      chloroplast envelope into the vacuole was noted in cells of vitrified leaves.

PMID- 9554583
TI  - High contrast and homogeneous staining of paraffin sections of whole human brains
      for three dimensional ultrahigh resolution image analysis.
AB  - The gallocyanin chromalum stain belongs to the classical DNA-RNA staining
      techniques in histochemistry. It has some important features for successful
      object orientated image analysis of whole sections of the human brain. To obtain
      reproducible staining results with these large sections, the method of Einarson
      was adapted to image analytical requirements. We discuss staining in a warm
      staining solution, pH adjustment, and optimal stain composition. The embedding
      procedure for whole human brains is considered as well.

PMID- 9554584
TI  - Improved osmication, dehydration and flat embedding of vibratome sections and
      delicate whole mount preparations.
AB  - A simple method for flat embedding vibratome sections or delicate whole mount
      preparations in epoxy resin is described that allows thin layers of interest
      within the specimen to be cut and studied as a whole in one plane. The fatal
      curling that occurs during dehydration was avoided or at least minimized by
      dehydrating the specimens in a layer of filter paper and a plastic meshwork under
      permanent slight pressure. The flatness of the structures was maintained through
      a graded series of ethanols followed by acetone. The specimens were transferred
      to the resin and polymerized between two coated glass slides making it possible
      to view and select the material without direct handling of the thin resin layer.

PMID- 9554586
TI  - Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca
      alkaloid.
AB  - Vinflunine, or 20',20'-difluoro-3',4'-dihydrovinorelbine, is a novel Vinca
      alkaloid obtained by hemisynthesis using superacidic chemistry. The most
      impressive structural modification of this vinorelbine derivative was the
      selective introduction of two fluorine atoms at the 20' position, a part of the
      molecule previously inaccessible by classic chemistry. The antitumor activity of
      vinflunine was evaluated against a range of transplantable murine and human
      tumors. Vinflunine exhibited marked activity against murine P388 leukemia grafted
      i.v. when given i.p. in single or multiple doses according to various schedules
      or in single i.v. or p.o. doses. Increases in life span achieved with vinflunine,
      as assessed by T/C ratios, ranged from 200% to 457% and proved markedly superior
      to those of 129-186% obtained with the other Vinca alkaloids tested. Against s.c.
      implanted B16 melanoma, multiple i.p. administration of vinflunine proved active
      in terms of both survival prolongation and tumor growth inhibition, with optimal
      T/C values and relative areas under the tumor growth curves (rAUC) being 24% and
      36%, respectively. The extent of this activity was superior to that noted for
      vinorelbine under the same experimental conditions. Growth inhibition of human
      tumor xenografts LX-1 (lung) and MX-1 (breast) was also observed following four
      weekly i.p. injections of vinflunine as reflected by optimal T/C values of 23%
      and 26%, respectively, and significant differences in the rAUCs noted for treated
      versus control animals. It was also noticeable that vinflunine induced
      considerably more prolonged inhibitory effects on tumor growth than did
      vinorelbine. These results demonstrate that vinflunine is well tolerated and is
      definitively active against a range of experimental animal tumor models.
      Vinflunine activity has been documented in terms of both survival prolongation
      and tumor growth inhibition, with definite superiority over vinorelbine being
      shown in each tumor model evaluated.

PMID- 9554585
TI  - Practical implementation of a modified continual reassessment method for dose
      finding trials.
AB  - PURPOSE: We describe a practical, reliable, efficient dose-finding design for
      cytotoxic drugs applied in a multi-institutional setting. METHODS: The continual
      reassessment method (CRM) was modified for use in phase I trials conducted
      through the New Approaches to Brain Tumor Therapy (NABTT) Consortium. Our
      implementation of the CRM uses (1) a simple dose-toxicity model to guide data
      interpolation, (2) groups of three patients to minimize calculations and
      stabilize estimates, (3) investigators' clinical knowledge or opinion in the form
      of data to make the process easier to understand, and (4) a flexible computer
      program and interface to facilitate calculations. RESULTS: The modified CRM was
      used in two dose-finding trials of 9-aminocamptothecin in patients with newly
      diagnosed and recurrent glioblastoma who were taking anticonvulsant medication.
      The CRM located the maximum tolerated dose (MTD) efficiently in both trials.
      Compared to conventional designs, the CRM required slightly more than half the
      number of patients expected, did not greatly overshoot the MTD (i.e. no patients
      were treated at dangerously high doses), and did not underestimate the MTD.
      CONCLUSIONS: Our experience demonstrates the feasibility of implementing this
      design in multi-institutional trials and the possibility of performing dose
      finding studies that require fewer patients than conventional methods.

PMID- 9554587
TI  - Sequence-dependent cytotoxicity of etoposide and paclitaxel in human breast and
      lung cancer cell lines.
AB  - PURPOSE: To evaluate the effect of schedule on the interaction of etoposide with
      paclitaxel in vitro against the A549 human lung cancer cell line and the MDA-231
      and MCF-7 human breast cancer cell lines. METHODS: Exposure schedules that were
      24-h concurrent, 24-h sequential, and sequential 24-h with a 24-h intervening
      drug-free period were quantitatively evaluated by the use of the median-effect
      principle and the combination index. The clonogenic assay was used to assess
      cytotoxicity, and calculations were done with computer software. RESULTS:
      Concurrent exposures were less than additive in two of the three cell lines
      tested. Sequential 24-hour and sequential 24-h with an intervening 24-h drug-free
      period showed synergism at high effect levels in all three cell lines. Similar
      synergistic interactions were found when either agent was administered first.
      CONCLUSIONS: These results show a schedule-dependent cytotoxic interaction
      between etoposide and paclitaxel in the human lung and breast cancer cell lines
      evaluated, with optimal synergism occurring with sequential, but not with
      concurrent, treatment.

PMID- 9554588
TI  - Phase II trial of combination chemotherapy with cisplatin, carboplatin and
      etoposide in stage IIIB and IV small-cell lung cancer. Fukuoka Lung Cancer Study
      Group.
AB  - PURPOSE: A phase II trial combining cisplatin, carboplatin and etoposide was
      conducted in previously untreated patients with stage IIIB and IV small-cell lung
      cancer, in an attempt to increase response rates and prolong survival. METHODS:
      Previously untreated patients with small-cell lung cancer, with measurable
      disease, aged < or = 72 years, performance status < or = 2, and adequate
      hematologic, hepatic and renal function were enrolled in the study. They were
      treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and
      8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8. RESULTS: A total of 46 patients
      (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A
      total of 186 courses of chemotherapy were given, and the dose was reduced in 27
      courses (15%). The chemotherapy was repeated for four or more courses in 30
      patients. There were 10 complete responses and 32 partial responses, for a total
      response rate of 91% (95% confidence interval, 79% to 98%). The median survival
      time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and
      14 months and 15% for stage IV disease. Major side effects were hematologic:
      leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%,
      and 43% of patients, respectively. CONCLUSIONS: The three-drug regimen of
      cisplatin, carboplatin and etoposide is feasible and active against small-cell
      lung cancer.

PMID- 9554589
TI  - Expression of Bcl-2 in human epithelial tumor (HeLa) cells enhances clonogenic
      survival following exposure to 5-fluoro-2'-deoxyuridine or staurosporine, but not
      following exposure to etoposide or doxorubicin.
AB  - A reduced capacity for apoptosis induction is considered to play a significant
      role both in the development of malignancy and in tumor cell resistance to
      chemotherapeutic drugs. The Bcl-2 oncoprotein inhibits apoptosis induced by
      antitumor agents at a point downstream of drug-target interactions. Stable
      expression of Bcl-2 in the human epithelial tumor (HeLa) cell line results in
      inhibition of apoptosis following exposure to the topoisomerase II poison,
      etoposide. However, Bcl-2 is unable to enhance clonogenic survival as a result of
      alternate pathways to reproductive death induced by the drug. PURPOSE: The
      purpose of this study was to further investigate the role of Bcl-2 in human
      epithelial tumor cell drug resistance using 5-fluoro-2'-deoxyuridine,
      staurosporine, and doxorubicin, in addition to etoposide. METHODS: The ability of
      Bcl-2 to enhance clonogenic cell survival was studied by colony-forming assays,
      while delay of cell death induction was assessed by trypan blue viability
      measurements. The proportion of apoptotic cells was measured by morphological
      criteria, as well as detection of apoptotic DNA fragmentation using the terminal
      deoxynucleotidyl transferase assay. RESULTS: Despite profound inhibition to loss
      of plasma membrane integrity for all agents tested, Bcl-2 was only able to
      significantly increase clonogenic survival following exposure to 5-fluoro-2'
      deoxyuridine and staurosporine, but not following exposure to etoposide or
      doxorubicin. Furthermore, the time-course of apoptosis induction following
      exposure of HeLa cells to equitoxic concentrations of staurosporine and etoposide
      was profoundly different. CONCLUSIONS: These results indicate that Bcl-2 enhances
      clonogenic survival of human epithelial tumor cells in an agent-specific fashion,
      which may be determined by the initial cytotoxic lesion induced by a particular
      drug.

PMID- 9554590
TI  - Plasma and cerebrospinal fluid pharmacokinetics of 9-aminocamptothecin (9-AC),
      irinotecan (CPT-11), and SN-38 in nonhuman primates.
AB  - PURPOSE: The plasma and cerebrospinal fluid (CSF) pharmacokinetics of the
      camptothecin analogs, 9-aminocamptothecin (9-AC) and irinotecan, were studied in
      a nonhuman primate model to determine their CSF penetration. METHODS: 9-AC, 0.2
      mg/kg (4 mg/m2) or 0.5 mg/kg (10 mg/m2), was infused intravenously over 15 min
      and irinotecan, 4.8 mg/kg (96 mg/m2) or 11.6 mg/kg (225 mg/m2), was infused over
      30 min. Plasma and CSF samples were obtained at frequent intervals over 24 h.
      Lactone and total drug forms of 9-AC, irinotecan, and the active metabolite of
      irinotecan, SN-38, were quantified by reverse-phase HPLC. RESULTS: 9-AC lactone
      had a clearance (CL) of 2.1 +/- 0.9 l/kg per h, a volume of distribution at
      steady state (Vd[ss]) of 1.6 +/- 0.7 l/kg and a half-life (t1/2) of 3.2 +/- 0.8
      h. The lactone form of 9-AC accounted for 26 +/- 7% of the total drug in plasma.
      The CSF penetration of 9-AC lactone was limited. CSF 9-AC lactone concentration
      peaked 30 to 45 min after the dose at 11 to 21 nM (0.5 mg/kg dose), and the ratio
      of the areas under the CSF and plasma concentration-time curves (AUC(CSF):AUC[P])
      was only 3.5 +/- 2.1%. For irinotecan, the CL was 3.4 +/- 0.4 l/kg per h, the
      Vd(ss) was 7.1 +/- 1.3 l/kg, and the t1/2 was 4.9 +/- 2.2 h. Plasma AUCs of the
      lactone form of SN-38 were only 2.0% to 2.4% of the AUCs of irinotecan lactone.
      The lactone form of irinotecan accounted for 26 +/- 5% of the total drug in
      plasma, and the lactone form of SN-38 accounted for 55 +/- 6% of the total SN-38
      in plasma. The AUC(CSF):AUC(P) ratio for irinotecan lactone was 14 +/- 3%. SN-38
      lactone and carboxylate could not be measured (< 1.0 nM) in CSF. The
      AUC(CSF):AUC(P) ratio for SN-38 lactone was estimated to be < or = 8%.
      CONCLUSION: Despite their structural similarity, the CSF penetration of 9-AC and
      SN-38 is substantially less than that of topotecan which we previously found to
      have an AUC(CSF):AUC(P) ratio of 32%.

PMID- 9554591
TI  - Differential effects of all-trans-retinoic acid, docosahexaenoic acid, and
      hexadecylphosphocholine on cisplatin-induced cytotoxicity and apoptosis in a
      cisplantin-sensitive and resistant human embryonal carcinoma cell line.
AB  - Apart from modulation of tumor-cell drug sensitivity, induction of
      differentiation might be an alternative in the treatment of tumors resistant to
      cytotoxic drugs. In this report the capacity to induce differentiation and to
      modulate the cis-diamminedichloroplatinum(II) (CDDP) sensitivity of all-trans
      retinoic acid (RA), docosahexaenoic acid (DCHA), and hexadecylphosphocholine
      (HePC) is examined in human germ-cell tumor cell lines. In the embryonal
      carcinoma cell line Tera-2 and its 3.7-fold CDDP-resistant subline Tera2-CP, we
      evaluated the effects of 96 h of pretreatment with RA (0.1 microM), DCHA (23
      microM), and HePC (25 microM) on differentiation induction and on CDDP-induced
      cytotoxicity, DNA platination (4-h incubation), and apoptosis (continuous
      incubation). Without drug treatment, Tera2-CP showed less apoptosis than Tera-2.
      Pretreatment with RA decreased the cytotoxicity and apoptosis induced by CDDP
      without resulting in decreased DNA platination and increased differentiation in
      both cell lines. DCHA enhanced CDDP-induced cytotoxicity and apoptosis and did
      not affect the embryonal character of either cell line. HePC did not affect CDDP
      cytotoxicity or differentiation in either cell lines. Effects of the modulators
      on differentiation and on CDDP-induced cytotoxicity, DNA platination, and
      apoptosis did not differ between Tera-2 and Tera2-CP. RA can be applied for
      differentiation induction in CDDP-resistant germ-cell tumor models. However, in
      this model, RA reduced the apoptotic susceptibility. DCHA potentiated CDDP
      cytotoxicity in vitro; its in vivo modulatory capacity in germ-cell tumor cells
      deserves further study.

PMID- 9554592
TI  - Clinical and pharmacokinetic studies of high-dose levamisole in combination with
      5-fluorouracil in patients with advanced cancer.
AB  - PURPOSE: To determine the maximum tolerable dose (MTD) and activity of levamisole
      administered concurrently with 5-fluorouracil (5-FU) in a standard 5-day course.
      To determine the pharmacokinetics of levamisole during the course of treatment.
      PATIENTS AND METHODS: Levamisole was administered to 38 patients orally three
      times a day for 5 days concurrently with a course of 5-FU administered daily by
      rapid intravenous injection for 5 days. Toxicity was evaluated in 20 patients who
      received escalating doses of levamisole. The activity of the combination was
      evaluated in 18 patients who received levamisole at the MTD with 5-FU. The
      pharmacokinetics of levamisole were characterized in ten patients at the MTD
      level. RESULTS: Intractable vomiting, confusion and vertigo were the major dose
      limiting toxicities. The MTD of oral levamisole was 100 mg/m2 administered three
      times a day concurrently with 450 mg/m2 per day intravenous 5-FU for 5
      consecutive days. Partial responses lasting 5 and 11 months were observed in 2/18
      patients with measurable disease at the MTD. Peak plasma concentrations of 1
      microg/ml (range 0.6-1.3 microg/ml) were achieved 90 min (range 60-360 min) after
      an oral dose of 100 mg/m2 levamisole with a 3.5-fold accumulation noted following
      4 days of administration. Peak plasma concentrations of p-hydroxylevamisole were
      about 5% of parent drug. Little parent drug (2-5%) was detected in urine.
      CONCLUSIONS: Levamisole may be administered safely with 5-FU at doses which are
      up to four to five times greater than those presently given in conventional
      regimens. The recommended dose of levamisole combined with 5-FU for future
      research protocols is 75 mg/m2 t.i.d for 5 days.

PMID- 9554593
TI  - Enhancement of irinotecan (CPT-11) activity against central nervous system tumor
      xenografts by alkylating agents.
AB  - Two major obstacles in the treatment of patients with central nervous system
      malignancies are drug resistance and host toxicity. The goal of combination
      chemotherapy is to achieve therapeutic effects that are more favorable than using
      a single drug alone, but without an increase in normal organ toxicity. The study
      reported here examined the combination of a topoisomerase I inhibitor, irinotecan
      (CPT-11), with three different alkylating agents: 1,3-bis(2-chloroethyl)-1
      nitrosourea, busulfan, and cyclophosphamide. We evaluated the antitumor effects
      of these three combinations against a panel of human tumor xenografts derived
      from central nervous system malignancies, including adult high-grade gliomas (D
      54 MG, D-245 MG) and a childhood ependymoma (D-612 EP). In replicate experiments,
      the alkylating agents were given on day 1 in doses varying from 10% to 75% of the
      dose lethal to 10% of the animals, and CPT-11 was given on days 1-5 and 8-12 in
      doses varying from 10% to 100% of the dose lethal to 10% of the animals. The
      antitumor effects of the various combinations ranged from less than additive
      (7.61 days below additive with 0.5 CPT-11 + 0.75 cyclophosphamide in D-54 MG) to
      statistically significant (P < 0.001) supraadditive effects (18.80 days above
      additive with 0.5 CPT-11 + 0.5 1,3-bis(2-chloroethyl)-1-nitrosourea in D-54 MG).
      These studies show that the combination of the topoisomerase inhibitor CPT-11 and
      alkylating agents may increase the antitumor effect in some cases well above
      additive with no increase in host toxicity (0/10 deaths in both experiments cited
      above) and should be considered for combination chemotherapy of central nervous
      system malignancies.

PMID- 9554594
TI  - Interactions of mild hyperthermia, cisplatin and split dose irradiation in human
      ovarian carcinoma cells.
AB  - PURPOSE: Human ovarian cancer cells were evaluated to determine whether
      combination treatment with mild hyperthermia and cisplatin could inhibit repair
      of sublethal radiation damage. MATERIALS AND METHODS: Human ovarian carcinoma
      cell lines A2780S (parental line) and A2780CP (cisplatin resistant variant) were
      used in this study. Cisplatin at concentrations of 1 or 3 microg/ml was given
      concomitantly with 1 h of heating at 40 degrees C either immediately before or
      after irradiation. Survival was determined using a colony-forming assay. RESULTS:
      Neither mild hyperthermia nor cisplatin treatments alone affected sublethal
      damage repair. The combined treatment showed an effect in both cell lines and was
      treatment sequence-dependent. The effect was greater in the parental cell line.
      CONCLUSIONS: The data show that combined treatment of cisplatin and hyperthermia
      may have clinical efficacy at cisplatin concentrations and hyperthermia
      temperatures which by themselves have little to no effect.

PMID- 9554595
TI  - Paclitaxel/carboplatin administration along with antiangiogenic therapy in non
      small-cell lung and breast carcinoma models.
AB  - INTRODUCTION: With the introduction of new drugs, the efficacy of chemotherapy in
      non-small-cell lung cancer has been improving. The combination of paclitaxel and
      carboplatin has shown activity in this disease but is far from curative. METHODS:
      The antiangiogenic agent regimen of TNP-470/minocycline was added to treatment
      with paclitaxel and carboplatin alone and in combination in animals bearing the
      Lewis lung carcinoma. RESULTS: Administration of the antiangiogenic regimen prior
      to, during and after the cytotoxic therapy increased the tumor growth delay 1.6
      fold and decreased the number of lung metastases to 20% of the number observed in
      the control animals. [14C]Paclitaxel, platinum from carboplatin and [14C]albumin
      levels were determined over a 24-h time course in tumors and normal tissues of
      animals bearing the Lewis lung carcinoma and pretreated with TNP-470/minocycline
      or not pretreated. There were higher levels of [14C]paclitaxel, platinum from
      carboplatin and [14C]albumin in the tumors and some normal tissues of the animals
      that had received TNP-470/minocycline compared with those that had not received
      TNP-470/minocycline, especially at the earlier time points. Administration of TNP
      470/minocycline to animals bearing the EMT-6 mammary carcinoma increased the
      cytotoxicity of high-dose paclitaxel toward EMT-6 tumor cells and toward bone
      marrow CFU-GM. Administration of TNP-470/minocycline to animals bearing the EMT-6
      mammary carcinoma also increased the cytotoxicity of carboplatin toward the EMT-6
      tumor cells but did not affect the toxicity of carboplatin toward the bone marrow
      CFU-GM. CONCLUSIONS: The addition of TNP-470/minocycline to treatment with
      paclitaxel and carboplatin resulted in increased antitumor activity and efficacy
      and further investigation of this combination is warranted.

PMID- 9554596
TI  - Effects of polyamine analogues on prostatic adenocarcinoma cells in vitro and in
      vivo.
AB  - PURPOSE: The overall purpose of this study was to determine the potential
      usefulness of 1,19-di-(ethylamino)-5,10,15-triazononadecane (BE-4-4-4-4) in the
      treatment of prostate cancer using in vitro and in vivo models. More specifically
      the objectives were: (1) to determine the in vitro and in vivo sensitivity of
      human and rat prostate cancer cells to two polyamine analogues N1,N11
      di(ethyl)norspermine (DENSPM) and BE-4-4-4-4; (2) to determine whether the
      mechanism of cell kill occurred through an apoptotic pathway; and (3) to
      determine the toxicity associated with therapeutic doses of BE-4-4-4-4 using an
      animal model. METHODS: In order to determine the ability of these drugs to cause
      in vitro cytotoxicity, colony-forming assays were performed utilizing the well
      characterized Dunning rat prostate cancer cell lines AT3.1, AT6.1 and AT6.3, and
      the androgen-insensitive human prostate cancer cell lines DU145, DuPro-1 and TSU
      Pr1. Apoptotic cell death was determined using DNA laddering and DAPI staining of
      nuclei. The antitumor activity of BE-4-4-4-4 was evaluated by treatment of DuPro-
      and PC-3 xenograft tumors in nude mice. RESULTS: BE-4-4-4-4 was shown to be
      approximately 4 to 86 times more cytotoxic in clonogenic assays than DENSPM in
      both rat and human prostate carcinoma cell lines. Cells treated with cytotoxic
      doses of DENSPM or BE-4-4-4-4 showed no signs of apoptosis using either DNA
      laddering or DAPI staining of nuclei. There was a significant inhibition of DuPro
      1 tumors for animals treated with BE-4-4-4-4 compared with control animals.
      Equitoxic doses of BE-4-4-4-4 resulted in greater tumor inhibition than DENSPM,
      although the difference was not significant. After treatment with therapeutic
      doses of BE-4-4-4-4, histopathologic evaluation indicated minimal to mild
      necrosis and inflammation in the kidneys on days 15 and 22 following treatment.
      On day 35, there was no necrosis or regeneration present in the kidney,
      indicating that the toxicity was transient and that regeneration of epithelial
      cells was complete with apparent return to normalcy. CONCLUSIONS: These initial
      studies demonstrate that BE-4-4-4-4 is cytotoxic against rat and human prostate
      cancer cells in culture and effective against DuPro-1 xenografts in nude mice.
      Polyamine analogues, such as DENSPM or BE-4-4-4-4, should be considered for
      clinical use in the treatment of prostate adenocarcinomas.

PMID- 9554597
TI  - High-dose-intensity combination chemotherapy for advanced sarcomas: a pilot
      study.
AB  - A new polychemotherapy schedule involving high dose intensity and shortened
      intervals has been developed for patients with advanced sarcomas. Mesna at 2500
      mg/m2 for 3 days, epidoxorubicin at 60 mg/m2 on day 1, ifosfamide at 2500 mg/m2
      for 3 days, and dacarbazine at 450 mg/m2 for 2 days were given every 2 weeks to a
      consecutive series of 20 patients. All patients received granulocyte colony
      stimulating factor (G-CSF; Filgrastim) subcutaneously at 300 microg from day 5 to
      day 12 of each cycle. The treatment was feasible and toxicity was acceptable,
      with grade IV myelotoxicity being observed only in one case. In all, 6 of 14
      evaluable patients had an objective response; the median survival was 12 months.
      Toxicity was milder than that observed for the classic combination MAID, and the
      planned dose intensity was maintained in the majority of cases.

PMID- 9554598
TI  - Effect of the multidrug resistance modulator valspodar on serum cortisol levels
      in rabbits.
AB  - PURPOSE: To contribute to a better understanding of the physiological role of P
      glycoprotein (P-gp) in the adrenal gland, we initiated our studies in rabbits.
      The aim of our study was to explore the effect of the selective multidrug
      resistance (MDR) modulator PSC 833 (valspodar) on serum cortisol in rabbits.
      METHODS: Baseline and corticotropin-stimulated serum cortisol levels were
      measured before and after valspodar treatment in adult male rabbits. Seven
      rabbits were treated with 50 mg/kg per dose and seven, with 75 mg/kg per dose of
      valspodar subcutaneously. Serum cortisol levels were determined by
      radioimmunoassay adjusted for expected values. RESULTS: Serum cortisol levels
      (baseline as well as corticotropin-stimulated) increased after both valspodar
      treatment regimens. The increase was dose-dependent and was higher for the
      baseline than for the corticotropin-stimulated values. Serum valspodar levels
      exceeding 1000 ng/ml were achieved in all except one animal in each group. We
      hypothesize that the increased serum cortisol levels were due to increased
      adrenocorticotropic hormone (ACTH) secretion after valspodar treatment, but,
      unfortunately, we could not measure ACTH properly in rabbits by means of the
      commercially available kits. CONCLUSIONS: Our study indicates that P-gp is not
      involved in steroid hormone secretion in the adrenal gland. This is evident from
      observations that serum cortisol levels were found to have increased rather than
      decreased in rabbits treated with a P-gp blocker and that the treated animals
      appeared healthy and normal. Since P-gp was found to play an important role in
      protection against xenobiotics in some other organs, further studies to explore
      the protective role of P-gp in the adrenal gland are warranted.

PMID- 9554599
TI  - Quantitative evaluation of multiplicity in epidemiology and public health
      research.
AB  - Epidemiologic and public health researchers frequently include several dependent
      variables, repeated assessments, or subgroup analyses in their investigations.
      These factors result in multiple tests of statistical significance and may
      produce type 1 experimental errors. This study examined the type 1 error rate in
      a sample of public health and epidemiologic research. A total of 173 articles
      chosen at random from 1996 issues of the American Journal of Public Health and
      the American Journal of Epidemiology were examined to determine the incidence of
      type 1 errors. Three different methods of computing type 1 error rates were used:
      experiment-wise error rate, error rate per experiment, and percent error rate.
      The results indicate a type 1 error rate substantially higher than the
      traditionally assumed level of 5% (p < 0.05). No practical or statistically
      significant difference was found between type 1 error rates across the two
      journals. Methods to determine and correct type 1 errors should be reported in
      epidemiologic and public health research investigations that include multiple
      statistical tests.

PMID- 9554600
TI  - Caffeine intake and low birth weight: a population-based case-control study.
AB  - The authors conducted a matched case-control study to investigate the effects of
      caffeine intake during pregnancy on birth weight. From January to November 1992,
      in the first 24 hours after delivery, 1,205 mothers (401 cases and 804 controls)
      were interviewed and their newborns were examined to assess birth weight and
      gestational age by means of the method of Capurro et al. (J Pediatr 1978;93:120
      2). The cases were children with birth weight < 2,500 g and gestational age > or
      = 28 weeks. Cases and controls were matched for time of birth and hospital of
      delivery and were recruited from the four maternity hospitals in Pelotas,
      southern Brazil. Daily maternal caffeine intake during pregnancy for each
      trimester was estimated. To assess caffeine intake, 10% of the mothers were
      reinterviewed at their households and samples of reported information on drip
      coffee and mate (a caffeine-containing drink widely used in South America) were
      collected and sent to the laboratory for caffeine determination through liquid
      chromatography. When instant coffee was reported, the weight of powder was
      measured using a portable scale, and caffeine intake was estimated from a
      reference table. Caffeine intake from tea, chocolate, soft drinks, and medicines
      was estimated from a reference table. Analyses were performed by conditional
      logistic regression. Crude analyses showed no effect of caffeine on low birth
      weight, preterm births or intrauterine growth retardation. The results did not
      change after allowing for confounders.

PMID- 9554601
TI  - Effects of physical activity on preterm birth.
AB  - The authors conducted a cohort study of low income women to determine the effect
      of physical activity on the risk of preterm birth. Women were sampled prenatally
      from four clinic sites and were scheduled for delivery at the University of
      Maryland Medical Systems (UMMS). Women who delivered infants at UMMS but who had
      received no prenatal care were also eligible. Preterm delivery was defined as a
      delivery prior to 37 completed weeks gestation. After adjusting for confounders,
      the odds of preterm delivery were increased for women who climbed stairs > or =
      10 times per day (odds ratio (OR) = 1.60, 95% confidence interval 1.05-2.46) and
      for women who engaged in purposive walking > or = 4 days per week (OR = 2.10, 95%
      CI 1.38-3.20). Leisure-time exercise (> or = 60 days in the first and second
      trimesters combined) had a protective effect on preterm delivery (OR = 0.51, 95%
      CI 0.27-0.95). Television viewing had a U-shaped relation with preterm delivery
      (ORs (95% CI): < 15 hours, 2.09 (1.21-3.61); 29-42 hours, 1.50 (0.84-2.67); > 42
      hours, 3.05 (1.75-5.40)). While the results support current recommendations
      regarding leisure-time activities, activities of daily living appear to increase
      risk of preterm delivery among low income women. These findings and those for
      television watching warrant further investigation.

PMID- 9554602
TI  - Menstrual cycle characteristics and history of ovulatory infertility in relation
      to breast cancer risk in a large cohort of US women.
AB  - Menstrual cycle characteristics and ovulatory infertility were evaluated in
      relation to breast cancer risk among 116,678 women in the Nurses' Health Study
      II, a prospective cohort study of female registered nurses who were aged 25-42
      years and living in 14 US states at enrollment in 1989. During 396,299 person
      years of follow-up between return of the baseline questionnaire and June 1993,
      251 cases of breast cancer were identified in this cohort. The multivariate
      relative risk (RR) associated with age at menarche > 13 years compared with age <
      or = 12 years was 0.66 (95% confidence interval (CI) 0.44-0.99). Short and long
      menstrual cycle lengths at ages 18-22 years were associated with reduced risk.
      Compared with menstrual cycle length 26-31 days, the multivariate relative risks
      (95% CIs) for more extreme cycle lengths were: < 26 days, 0.50 (0.25-0.98); 32-39
      days, 0.81 (0.51-1.28); and > 39 days or too irregular for estimation of a usual
      cycle length, 0.41 (0.18-0.94). The multivariate relative risk associated with a
      history of ovulatory infertility, compared with no such history, was 0.41 (95% CI
      0.18-0.93). These results are consistent with the hypothesis that reduced
      exposure to ovulatory menstrual cycles provides a protective effect against
      breast cancer.

PMID- 9554603
TI  - Body mass index, cigarette smoking, and other characteristics as predictors of
      self-reported, physician-diagnosed gallbladder disease in male college alumni.
AB  - Despite the high prevalence of gallbladder disease in industrialized countries,
      little is known about the predictors of the disease, especially in men. The
      authors prospectively studied 16,785 alumni of Harvard University, aged 15-24
      years, who were followed for up to 61 years. The health characteristics of these
      men were ascertained from their college entrance physical examination done in
      1916-1950, and updated via mailed questionnaires in 1962 or 1966 (1962/1966).
      Alumni subsequently self-reported physician-diagnosed gallbladder disease on
      further mailed questionnaires in 1972 or 1977. Between college time and
      1962/1966, 371 gallbladder disease cases occurred. An additional 314 cases
      occurred after 1962/1966. With respect to college characteristics, after
      adjustment for potential confounders, the authors found that body mass index
      (BMI), smoking, physical activity, blood pressure, and consumption of alcohol,
      coffee, or tea were unrelated to risk. However, BMI in 1962/1966 was directly
      related to risk of subsequent gallbladder disease, as was BMI gain since college
      (p, trend = 0.002 and 0.013, respectively). Compared with men with BMI < 22.0,
      men with BMI > or = 27.0 had a rate ratio of 2.71 (95% confidence interval (CI)
      1.57-4.66) for risk of contracting the disease. Men who gained > or = 6.0 BMI
      units since college had a rate ratio of 1.46 (95% CI 0.86-2.46) compared with men
      who gained -0.9 to +0.9 BMI units. Compared with never smokers, men who smoked
      pipes or cigars or < 1 pack of cigarettes daily in 1962/1966 had a rate ratio of
      1.43 (95% CI 1.00-2.06), while heavier cigarette smokers had a rate ratio of 1.52
      (95% CI 1.03-2.24). Neither physical activity nor physician-diagnosed
      hypertension or diabetes mellitus in 1962/1966 predicted risk.

PMID- 9554604
TI  - Family history score as a predictor of breast cancer mortality: prospective data
      from the Cancer Prevention Study II, United States, 1982-1991.
AB  - A consistent predictor of a woman's risk for breast cancer is a family history of
      the disease. Most studies of family history and breast cancer have used the
      number of affected relatives in the family to calculate relative risk, but they
      have not considered the heterogeneity of the familial risk for breast cancer in a
      systematic way. With the use of data from a large prospective mortality study of
      US adults, the authors compared simple classification of family history of breast
      cancer (yes/no) to the method of using a quantitative family history score
      method, which takes into account the effects of family structure, age, and birth
      cohort as predictors of breast cancer mortality. After 9 years of follow-up,
      1,428 cases of fatal breast cancer were observed among 453,073 women with
      complete information on number and age of siblings and family history. With the
      use of the family history score, about one-third of women with a positive family
      history of breast cancer were at no higher risk for breast cancer mortality than
      those without a family history of the disease. As a quantitative measure of
      relative risk for each family, family history score gave a better fit to the
      data, and it provided an incremental improvement of predictive accuracy of
      developing fatal breast cancer. Family history score can also be used as a
      categorical variable to stratify families. This allows researchers to focus on
      which risk groups would benefit from conducting further genetic analysis and to
      test the effects of genetic factors, environmental exposure, and gene-environment
      interactions on the etiology of the development of breast cancer.

PMID- 9554605
TI  - Marked increase in bladder and lung cancer mortality in a region of Northern
      Chile due to arsenic in drinking water.
AB  - Studies in Taiwan and Argentina suggest that ingestion of inorganic arsenic from
      drinking water results in increased risks of internal cancers, particularly
      bladder and lung cancer. The authors investigated cancer mortality in a
      population of around 400,000 people in a region of Northern Chile (Region II)
      exposed to high arsenic levels in drinking water in past years. Arsenic
      concentrations from 1950 to the present were obtained. Population-weighted
      average arsenic levels reached 570 microg/liter between 1955 to 1969, and
      decreased to less than 100 microg/liter by 1980. Standardized mortality ratios
      (SMRs) were calculated for the years 1989 to 1993. Increased mortality was found
      for bladder, lung, kidney, and skin cancer. Bladder cancer mortality was markedly
      elevated (men, SMR = 6.0 (95% confidence interval (CI) 4.8-7.4); women, SMR = 8.2
      (95% CI 6.3-10.5)) as was lung cancer mortality (men, SMR = 3.8 (95% CI 3.5-4.1);
      women, SMR = 3.1 (95% CI 2.7-3.7)). Smoking survey data and mortality rates from
      chronic obstructive pulmonary disease provided evidence that smoking did not
      contribute to the increased mortality from these cancers. The findings provide
      additional evidence that ingestion of inorganic arsenic in drinking water is
      indeed a cause of bladder and lung cancer. It was estimated that arsenic might
      account for 7% of all deaths among those aged 30 years and over. If so, the
      impact of arsenic on the population mortality in Region II of Chile is greater
      than that reported anywhere to date from environmental exposure to a carcinogen
      in a major population.

PMID- 9554606
TI  - Obesity, weight gain, large weight changes, and adenomatous polyps of the left
      colon and rectum.
AB  - Epidemiologic studies of colorectal neoplasia have usually examined body mass
      index as a risk factor, but not other aspects of obesity. During 1991-1993, the
      authors obtained weight histories and comprehensive covariate data from men and
      women aged 50-75 years who underwent sigmoidoscopy at a health maintenance
      organization in southern California. Using 483 cases with adenomas and 483
      controls, measures of obesity (body mass index), positive energy balance (net
      weight gain in the past 10 years), and weight variability (large weight changes)
      were each independently related to adenoma prevalence. Compared with subjects in
      the lowest quartile of body mass index, multivariate-adjusted odds ratios for
      subjects in increasingly higher quartiles were 2.1 (95% confidence interval (CI)
      1.4-2.3), 1.8 (1.1-2.9), and 1.7 (1.0-2.8), respectively. Compared with subjects
      who reported a net weight loss during the 10 years before sigmoidoscopy, subjects
      with net weight gains of 1.5-4.5 kg or > or = 4.5 kg had adjusted odds ratios
      (95% CI) of 2.5 (1.2-5.6) and 1.8 (0.7-4.4), respectively. Compared with subjects
      who had no large weight changes during adulthood, subjects with 1-2, 3, or > or =
      4 changes had adjusted odds ratios (95% CI) of 2.0 (1.0-3.9), 2.5 (1.2-5.5), and
      1.5 (0.6-3.6), respectively. Obesity, weight gain, and unstable adult weight may
      be independently associated with colorectal carcinogenesis.

PMID- 9554607
TI  - Selection bias in occupational sperm studies.
AB  - Participation rates in sperm studies are typically 25-50%, and therefore it is a
      matter of concern whether the men who provide semen samples truly reflect the
      parent population. The authors analyzed data from three Danish occupational sperm
      studies and evaluated the relation between age and occurrence of subfertility to
      participation and provision of semen samples. Age and subfertility were found to
      be rather strong determinants of participation. Willingness to provide semen
      samples was greater among men aged <40 years (odds ratio (OR) = 1.8, 95%
      confidence interval (CI) 1.3-2.6) and among men who had experienced an infertile
      period (OR = 1.7, 95% CI 1.3-2.1). Furthermore, the effect of infertility was
      modified by occupational exposure status, thus resulting in a tendency to
      differential selection and possibly biased risk estimates. In a cross-sectional
      study, the authors recommend that priority be given to a high participation rate
      and that data on the basic variables be collected from the entire study
      population, so that it is possible to make a nonresponder analysis and evaluate
      bias. Such an analysis can be carried out by means of questions enquiring about
      infertility, genital disorders, and earlier seminal examinations. Although the
      longitudinal study design is without many of the limitations of the cross
      sectional study, a longitudinal study is usually not feasible.

PMID- 9554608
TI  - Association of a central pattern of body fat with blood pressure and lipoproteins
      from adolescence into adulthood. The Amsterdam Growth and Health Study.
AB  - The association between the change in a central pattern of body fat and blood
      pressure and lipoprotein levels was investigated longitudinally in a healthy
      population of young males and females over 15 years. The subjects (males, n = 84;
      females, n = 98), participants in the Amsterdam Growth and Health Study, were
      measured six times between the mean ages of 13 and 27 years. As an indicator of a
      central pattern of body fat, subscapular/triceps skinfold ratio (S/T ratio) was
      used as an independent variable. Systolic blood pressure (SBP), diastolic blood
      pressure (DBP), total serum cholesterol (TC), high density lipoprotein
      cholesterol (HDL-C), and TC/HDL-C ratio were used as dependent variables.
      Longitudinal associations were analyzed by generalized estimating equations (GEE)
      in which data of the six periods of measurement were included simultaneously.
      Between ages 13 and 27 years, and after adjustment for the sum of four skinfolds,
      physical activity, smoking, and alcohol intake, the increase of the S/T ratio was
      significantly associated with an increase in SBP in males and females and with a
      decrease in level of HDL-C in males only. The change in central pattern of body
      fat negatively affects the change in established risk factors for cardiovascular
      diseases early in life.

PMID- 9554609
TI  - Comparison of population-averaged and subject-specific approaches for analyzing
      repeated binary outcomes.
AB  - Several approaches have been proposed to model binary outcomes that arise from
      longitudinal studies. Most of the approaches can be grouped into two classes: the
      population-averaged and subject-specific approaches. The generalized estimating
      equations (GEE) method is commonly used to estimate population-averaged effects,
      while random-effects logistic models can be used to estimate subject-specific
      effects. However, it is not clear to many epidemiologists how these two methods
      relate to one another or how these methods relate to more traditional stratified
      analysis and standard logistic models. The authors address these issues in the
      context of a longitudinal smoking prevention trial, the Midwestern Prevention
      Project. In particular, the authors compare results from stratified analysis,
      standard logistic models, conditional logistic models, the GEE models, and random
      effects models by analyzing a binary outcome from two and seven repeated
      measurements, respectively. In the comparison, the authors focus on the
      interpretation of both time-varying and time-invariant covariates under different
      models. Implications of these methods for epidemiologic research are discussed.

PMID- 9554610
TI  - Adult female twins' recall of childhood social class and father's education: a
      validation study for public health research.
AB  - To assess recall of childhood socioeconomic position for public health research,
      the authors conducted a cross-sectional study of 352 adult women twin pairs
      enrolled in Examination II of the Kaiser Permanente Women Twins Study carried out
      in 1989-1990 in Oakland, California. Among twin pairs, 91% (95% confidence
      interval (CI) 89-94%) agreed on their father's educational level and 81% (95% CI
      77-85%) on their childhood social class. Recall did not differ by adult
      socioeconomic position, zygosity, race/ethnicity, or age. Thus, epidemiologic
      studies can validly use retrospective data on childhood socioeconomic position to
      study its relation to adult health status.

PMID- 9554611
TI  - Geographic epidemiology of gonorrhea in Baltimore, Maryland, using a geographic
      information system.
AB  - The epidemiology of gonorrhea is characterized by geographically defined
      hyperendemic areas, or "cores." Geographic information system (GIS) technology
      offers new opportunities to evaluate these patterns. The authors developed a GIS
      system linked to the disease surveillance database at the Baltimore Health
      Department and used this system to evaluate the geographic epidemiology of
      gonorrhea in Baltimore, Maryland, during 1994. There were 7,330 reported cases,
      of which 87.4% were in persons aged 15-39 years; 56.6% were of the cases were in
      males; and 60.5% of the cases were reported from the nonsexually transmitted
      disease (STD) clinic sector. Valid residential addresses were available for 6,831
      (93.5%) of cases. In the GIS system, gonorrhea cases were geocoded by reported
      address using digitized maps, and assigned to census tract. Census tract-specific
      rates for persons aged 15-39 years were calculated using 1990 census data.
      Gonorrhea was reported from 196/202 (97%) of census tracts, of which 90 census
      tracts had >30 cases. For these 90 census tracts, rates were ranked. The core was
      considered as the top rate quartile, consisting of 13 geographically contiguous
      census tracts with rates 4,370-6,370 per 100,000; adjacent areas were 19 census
      tracts in the second quartile (rates: 3,730-4,370 per 100,000). As radial
      distance from the core areas increased, incidence rates decreased and male/female
      ratio increased, which is consistent with previous definitions of the core theory
      of STD transmission. Mapping of cases by provider showed that cases reported from
      STD clinics had similar geographic distribution to those from the non-STD clinic
      sector. From an operational perspective, GIS can be effectively integrated with
      clinical data systems to provide epidemiologic analysis.

PMID- 9554612
TI  - Mechanisms of acute epicardial and myocardial injury in pericardial disease.

PMID- 9554613
TI  - Preoperative smoking reduction: all or nothing at all?

PMID- 9554614
TI  - Use of the breathing reserve to interpret submaximal exercise responses.

PMID- 9554615
TI  - It's not "just a virus" anymore.

PMID- 9554616
TI  - The acute effect of minocycline on the pericardium: experimental and clinical
      findings.
AB  - STUDY OBJECTIVES: To evaluate the acute effect of minocycline on the pericardium
      in the experimental animal and in the human with malignant pericardial disease.
      DESIGN: A prospective study in open-chest dogs and in humans. SETTING:
      Experimental surgery laboratory, medical school; coronary care unit, university
      hospital. METHODS: Twenty-three open-chest dogs were divided into four groups
      according to the solution injected intrapericardially: (1) minocycline, 5 mg/kg;
      (2) minocycline, 10 mg/kg; (3) normal saline solution, 100 mL, followed by
      minocycline, 10 mg/kg; (4) a mixture of 50 mL of the dog's own blood mixed ex
      vivo with minocycline, 10 mg/kg to evaluate the effect of rising pH of
      minocycline solution. The extent of myocardial injury is evaluated by measuring
      ST-T segment deviation in six standard bipolar leads and in three unipolar
      electrograms recorded over the left ventricular pericardial surface. The pH of
      the various minocycline solutions is measured. Nine consecutive patients with
      malignant cardiac tamponade receiving minocycline intrapericardially are
      evaluated for the appearance of chest pain and ECG changes. RESULTS: Minocycline
      (5 and 10 mg/kg) caused marked, transient ST-T segment deviation in all dogs,
      whether or not saline solution was previously injected into the pericardial sac.
      Prior mixing of minocycline with blood markedly increased the acidic pH of the
      minocycline solution and significantly reduced the extent of ST-T segment
      deviation. Four of nine patients had chest pain during minocycline injection.
      None had ST-T segment changes. CONCLUSION: Minocycline causes a marked, transient
      injury to the epicardial-pericardial surface. Our animal and in vitro studies
      indicate that this acute injury is probably partly related to the acidic pH of
      the minocycline solution. Our experimental findings suggest that this minocycline
      induced injury may be reduced by raising the pH of the solution either ex vivo
      (eg, by mixing minocycline with previously withdrawn pericardial fluid) or in
      vivo (eg, by leaving 200 to 300 mL of pericardial fluid prior to minocycline
      injection). Limited experience in the human with malignant cardiac tamponade
      indicates that intrapericardial minocycline is usually well tolerated, although
      severe chest pain may appear.

PMID- 9554617
TI  - Normal left ventricular ejection fraction in older persons with congestive heart
      failure.
AB  - STUDY OBJECTIVES: To investigate in older patients with congestive heart failure
      (CHF) associated with prior myocardial infarction or hypertension the
      relationship between normal left ventricular (LV) ejection fraction and age,
      gender, hypertension, prior myocardial infarction, and atrial fibrillation.
      DESIGN: A prospective study was performed in 572 older patients (age >60 years)
      with CHF associated with prior myocardial infarction or hypertension and
      technically adequate two-dimensional echocardiograms for measuring LV ejection
      fraction. SETTING: A long-term health-care facility. PATIENTS: One hundred
      seventy-seven men and 395 women, mean age 82+/-8 years, with CHF associated with
      prior myocardial infarction or hypertension. MEASUREMENTS AND RESULTS: Normal LV
      ejection fraction (> or = 50%) occurred in 66 of 177 men (37%) and in 221 of 395
      women (56%) (p<0.0001). Multiple logistic regression analysis showed that
      independent risk factors for normal LV ejection fraction in patients with CHF
      were no prior myocardial infarction (p=0.0001; odds ratio=3.048), female gender
      (p=0.0004; odds ratio=1.978), and age (p=0.016; odds ratio=1.029). CONCLUSIONS:
      Normal LV ejection fraction occurred in 50% of 572 older patients with CHF
      associated with prior myocardial infarction or hypertension. Independent risk
      factors for normal LV ejection fraction in patients with CHF were no prior
      myocardial infarction, female gender, and age.

PMID- 9554618
TI  - Left ventricular-arterial system coupling at peak exercise in dilated nonischemic
      cardiomyopathy.
AB  - We assessed the ventricular-arterial coupling at peak exercise in 20 patients
      with dilated cardiomyopathy (ejection fraction, 27+/-12%) and 7 normal subjects
      by radionuclide ventriculography during exercise, coupled with respiratory gas
      analysis. The end-systolic pressure-volume ratio, taken as an index of
      contractility, and the effective arterial elastance were calculated at rest and
      at peak exercise. The end-systolic pressure/volume ratio increased from 3.7+/-2.7
      to 6.9+/-4.0 mm Hg/mL at peak exercise in the normal subjects, but did not change
      significantly (from 0.9+/-0.5 to 1.0+/-0.6 mm Hg/mL) in the patients. Arterial
      elastance did not change significantly in the patients (+17+/-32%, not
      significant [NS] vs rest) or in the normal subjects (+22+/-28%, NS vs rest). The
      change in ejection fraction during exercise correlated both with the end-systolic
      pressure/volume ratio and with effective arterial elastance changes (r=0.60 and
      0.68, respectively). We conclude that ventricular arterial coupling is further
      altered at peak exercise in these patients because of the lack of increase in
      contractility and not of altered effective arterial elastance response.

PMID- 9554619
TI  - Coronary artery bypass grafting in patients with COPD.
AB  - OBJECTIVE: To more fully define the influence of COPD in patients undergoing
      coronary artery bypass grafting (CABG). METHODS: One hundred ninety-one patients
      with COPD underwent CABG from March 1, 1995, to June 21, 1996. There were 129
      male and 62 female patients. The mean age was 69 years (45 to 86 years). Patients
      with COPD were defined according to the Summit Database definition: requires
      therapy for the treatment of chronic pulmonary compromise or has an FEV1 <75% of
      predicted value. RESULTS: Hospital mortality was 7%. Hospital morbidity was 50%.
      Statistically significant (p<0.05) morbidity included general pulmonary
      complications (12%) and atrial fibrillation (27%). Hospital mortality for COPD
      patients with postoperative pneumonia was 11%. Hospital mortality for patients
      with COPD receiving steroids was 19%. The hospital mortality for patients > or =
      75 years of age was 17%. The combined mortality for patients with COPD who are >
      or = 75 years of age and receiving steroid therapy was 50%. The mean length of
      stay was 12 days. Late mortality was 1% at a mean of 1.5 years. CONCLUSIONS:
      Hospital mortality in most patients with mild-to-moderate COPD undergoing CABG is
      similar to those without COPD. In the minority of patients with severe COPD who
      are receiving steroids and > 75 years, the hospital mortality is exceptionally
      high. These findings support CABG in patients with mild-to-moderate COPD.
      Nonsurgical therapy should be considered for elderly COPD patients with severe
      disease taking steroids.

PMID- 9554620
TI  - Preoperative smoking habits and postoperative pulmonary complications.
AB  - OBJECTIVE: To examine the effect of preoperative smoking behavior on
      postoperative pulmonary complications. DESIGN: Prospective cohort study. SETTING:
      The Veterans Administration Medical Center, Syracuse, NY. PARTICIPANTS: Patients
      scheduled for noncardiac elective surgery (n=410). MEASUREMENTS AND RESULTS:
      Smoking status was determined by self-report. Postoperative pulmonary
      complications were determined by systematic extraction of medical record data.
      Postoperative pulmonary complications occurred in 31 of 141 (22.0%) current
      smokers, 24 of 187 (12.8%) past smokers, and 4 of 82 (4.9%) never smokers. The
      odds ratio (OR) for developing a postoperative pulmonary complication for current
      smokers vs never smokers was 5.5 (95% confidence interval [CI], 1.9 to 16.2) and
      4.2 (95% CI, 1.2 to 14.8) after adjustment for type of surgery, type of
      anesthesia, abnormal chest radiograph, chronic cough, history of pulmonary
      disease, history of cardiac disease, history of COPD, education level, pulmonary
      function, body mass index, and age. Current smokers who reported reducing
      cigarette consumption prior to surgery were more likely to develop a complication
      compared with those who did not (adjusted OR=6.7, 95% CI, 2.6 to 17.1).
      CONCLUSIONS: Current smoking was associated with a nearly sixfold increase in
      risk for a postoperative pulmonary complication. Reduction in smoking within 1
      month of surgery was not associated with a decreased risk of postoperative
      pulmonary complications.

PMID- 9554621
TI  - Comparison of short-term functional outcomes following unilateral and bilateral
      lung volume reduction surgery.
AB  - STUDY OBJECTIVES: To compare short-term functional outcomes following unilateral
      and bilateral lung volume reduction surgery (LVRS) performed in patients with
      advanced emphysema. METHODS: LVRS was performed unilaterally in 32 patients and
      bilaterally in 119 patients. Pulmonary function testing and 6-min walk test
      (6MWT) were performed preoperatively and repeated at 3 to 6 months
      postoperatively. RESULTS: Bilateral LVRS was associated with increased in
      hospital mortality (10% vs 0%, p<0.05) and a higher incidence of postoperative
      respiratory failure (12.6% vs 0%; p<0.05) compared with unilateral LVRS. There
      was no significant difference in duration of air leaks between unilateral and
      bilateral groups, but the mean hospital stay was significantly longer following
      bilateral LVRS (21.1+/-32.0 days vs 14.2+/-14.0 days; p<0.05). Preoperatively,
      there was no significant difference between the unilateral and bilateral groups
      with respect to FEV1, FVC, residual volume, or 6MWT distance. However, for all of
      these parameters, the magnitude of improvement was significantly greater
      following bilateral LVRS. Notably, the magnitude of improvement in each parameter
      following unilateral LVRS exceeded half that following bilateral LVRS, suggesting
      that functional outcomes after the unilateral procedure were disproportionate to
      the amount of tissue resected. Serial functional assessment of seven patients
      undergoing staged unilateral procedures (two unilateral procedures separated in
      time by at least 3 months) demonstrated somewhat unpredictable responses; failure
      to achieve a favorable response to the initial procedure did not necessarily
      portend a similar outcome with the contralateral side, and vise versa.
      CONCLUSIONS: Bilateral LVRS produces a greater magnitude of short-term functional
      improvement than does the unilateral procedure and should be considered the
      procedure of choice for most patients. Unilateral LVRS should be reserved for
      patients in whom factors contraindicating entrance into one hemithorax exist.

PMID- 9554622
TI  - Lung volume reduction surgery: an analysis of hospital costs.
AB  - OBJECTIVE: Lung volume reduction surgery (LVRS) represents a potential
      breakthrough in the management of advanced emphysema, although questions remain
      about clinical and economic implications of widespread application of LVRS. In
      this report, we describe hospital costs, excluding physicians' fees, for LVRS.
      DESIGN: Hospital charges were obtained from billing records and converted to
      costs by applying multiple cost-to-charge ratios. SETTING: A large, urban
      academic medical center. PATIENTS: Fifty-two consecutive patients who received
      bilateral LVRS through a median sternotomy between April 1995 and August 1996.
      RESULTS: Median hospital stay was 10 days (mean= 14.8+/-12.8 days; range=3 to 48
      days), including 2 days (mean=6+/-9.2 days; range=1 to 35 days) in the ICU. One
      hospital death occurred. Hospital costs per case ranged from $11,712 to $121,829,
      with mean costs of $30,976 and median costs of $19,771. Costs were related
      significantly to duration of ICU stay and length of hospitalization. Patients who
      accrued the highest costs were significantly older than the remainder of the
      sample (69.3 years vs 62.4 years). CONCLUSIONS: Hospital costs of LVRS vary
      significantly but are related directly to hospital stay. Identification of
      factors associated with prolonged stays can be used in assessing benefits and
      risks of LVRS against utilization of health-care dollars.

PMID- 9554623
TI  - Impaired skeletal muscle endurance related to physical inactivity and altered
      lung function in COPD patients.
AB  - STUDY OBJECTIVE: The aims of this work were to determine (1) whether patients
      with COPD have impaired skeletal muscle performance (ie, maximal strength and
      endurance) compared with healthy subjects, and (2) whether the level of physical
      activity, body composition, and lung function are related to skeletal muscle
      performance in COPD patients. METHODS: Seventeen COPD patients and eight healthy
      age-matched control subjects performed maximum voluntary contraction (MVC) of the
      quadriceps and an endurance test consisting of dynamic contractions of the
      quadriceps against 20% of MVC at an imposed regular pace until exhaustion. The
      endurance test duration determined the muscle "limit time" (Tlim). A score of
      physical activity (PA score) was obtained using an adapted physical activity
      questionnaire for the elderly, and body composition was measured by the
      bioelectrical impedance method. Symptom-limited oxygen uptake (VO2 sl) was also
      assessed in COPD patients using a maximal incremental exercise test. RESULTS: The
      results showed that Tlim and PA score were significantly decreased in COPD
      patients (p<0.05). Significant positive correlations were found in the COPD group
      between Tlim and the PA score (r=0.60; p<0.05), FEV1 (r=0.52; p<0.05), and PaO2
      (r=0.63; p<0.05). The same results were found between the PA score and VO2 sl
      (r=0.57; p<0.05) and FEV1 (r=0.63; p<0.05). CONCLUSION: These findings indicate
      impaired skeletal muscle endurance in COPD patients related to altered lung
      function and associated physical inactivity.

PMID- 9554624
TI  - Aerobic endurance training program improves exercise performance in lung
      transplant recipients.
AB  - STUDY OBJECTIVE: To determine whether an aerobic endurance training program (AET)
      in comparison to normal daily activities improves exercise capacity in lung
      transplant recipients. PATIENTS AND STUDY DESIGN: Nine lung transplant recipients
      (12+/-6 months after transplant) were examined. All patients underwent
      incremental bicycle ergometry with the work rate increased in increments of 20 W
      every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal
      daily activities and then after a 6-week AET. The weekly aerobic training time
      increased from 60 min at the beginning to 120 min during the last week. Training
      intensity ranged from 30 to 60% of the maximum heart rate reserve. RESULTS:
      Normal daily activities had no effect on exercise performance. The AET induced a
      significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min.
      At an identical, submaximal level of exercise, a significant decrease in minute
      ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to
      133+/-17 beats/min, before and after the AET, was noted. The increase in peak
      oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27
      L/min). CONCLUSIONS: These data demonstrate that normal daily activities do not
      affect exercise performance in lung transplant recipients > or = 6 months after
      lung transplantation. An AET improves submaximal and peak exercise performance
      significantly.

PMID- 9554625
TI  - Breathing reserve at the lactate threshold to differentiate a pulmonary
      mechanical from cardiovascular limit to exercise.
AB  - STUDY OBJECTIVES: Criteria used to define the respective roles of pulmonary
      mechanics and cardiovascular disease in limiting exercise performance are usually
      obtained at peak exercise, but are dependent on maximal patient effort. To
      differentiate heart from lung disease during a less effort-dependent domain of
      exercise, the predictive value of the breathing reserve index (BRI=minute
      ventilation [VE]/maximal voluntary ventilation [MVV]) at the lactate threshold
      (LT) was evaluated. DESIGN: Thirty-two patients with COPD and a pulmonary
      mechanical limit (PML) to exercise defined by classic criteria at maximum oxygen
      uptake (VO2max) were compared with 29 patients with a cardiovascular limit (CVL)
      and 12 normal control subjects. Expired gases and VE were measured breath by
      breath using a commercially available metabolic cart (Model 2001; MedGraphics
      Corp; St. Paul, Minn). Arterial blood gases, pH, and lactate were sampled each
      minute during exercise, and cardiac output (Q) was measured by first-pass
      radionuclide ventriculography (System 77; Baird Corp; Bedford, Mass) at rest and
      peak exercise. RESULTS: For all patients, the BRI at lactate threshold (BRILT)
      correlated with the BRI at VO2max (BRIMAX) (r=0.85, p<0.0001). The BRILT was
      higher for PML (0.73+/-0.03, mean+/-SEM) vs CVL (0.27+/-0.02, p<0.0001), and vs
      control subjects (0.24+/-0.03, p<0.0001). A BRILT > or = 0.42 predicted a PML at
      maximum exercise, with a sensitivity of 96.9%, a specificity of 95.1%, a positive
      predictive value of 93.9%, and a negative predictive value of 97.5%. CONCLUSIONS:
      The BRILT, a variable measured during the submaximal realm of exercise, can
      distinguish a PML from CVL.

PMID- 9554626
TI  - Cytomegalovirus pneumonia in AIDS patients: value of cytomegalovirus culture from
      BAL fluid and correlation with lung disease.
AB  - OBJECTIVES: To verify the value of cytomegalovirus (CMV) cultures of BAL fluid vs
      postmortem lung histopathology in detecting CMV pneumonia, and to correlate the
      BAL viral dose with the number of CMV inclusion bodies (CMV-IB) in the lung
      tissue of AIDS patients. DESIGN: Retrospective analysis of 434 BALs and 40
      autopsies involving 307 AIDS patients; clinical follow-up lasted 10 months.
      PATIENTS AND METHODS: The 40 patients who died within 20 days of undergoing BAL
      were divided on the basis of histopathologic findings into subjects with and
      without CMV-IB in the lung tissue. The relationship between the BAL viral dose
      and CMV lung infection was evaluated by counting the early antigen (CMV-EA)
      positive cells/200 microL of BAL and the number of CMV-IB/mm2 of lung tissue.
      RESULTS: The predictive value of BAL virus isolation for the diagnosis of CMV
      pneumonia was 61% for positive and 100% for negative results. The patients with
      the largest number of CMV-IB had CMV-EA counts from 2 to 840; in those with a
      moderate and small number, the CMV-EA counts were, respectively, from 11 to 700
      and 2 to 300. Among the patients surviving up to 10 months after the BAL index
      sample, the frequency of recurrent extrapulmonary CMV abnormalities was 27% in
      those with positive and 7% in those with negative cultures. CONCLUSIONS: BAL CMV
      cultures from AIDS patients have a very high negative and relatively low positive
      predictive value for CMV pneumonia. The presence and replication of CMV in the
      lung may lead to systemic dissemination as suggested by the higher probability of
      CMV extrapulmonary diseases. Viral titers do not seem to be related to the degree
      of lung damage.

PMID- 9554627
TI  - Cytomegalovirus viremia in lung transplant recipients receiving ganciclovir and
      immune globulin.
AB  - BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of organ
      transplant-related morbidity and mortality. During the last 5 years at our
      institution, prophylactic ganciclovir and hyperimmune globulin have been
      routinely administered to lung transplant recipients whenever the donor or the
      recipient was CMV antibody-positive. We sought to assess the efficacy of
      prophylaxis on viremia, CMV disease, and bronchiolitis obliterans syndrome (BOS).
      METHODS: A retrospective chart review of 61 consecutive lung transplants
      performed between recipients between January 1993 and August 1995 was performed.
      Fifty-six patients who survived at least 1 month were analyzed. Patients were
      considered at risk for CMV disease whenever pretransplant donor or recipient
      serology was positive. RESULTS: Fourteen of the 39 patients at risk (36%) had
      viremia while on prophylaxis. The rate of CMV disease was 13% during the first 6
      months following transplantation. A donor whose CMV serology was positive
      appeared to increase the risk of BOS in a Cox regression model (relative
      risk=2.4; 95% confidence interval=0.86-6.74; p=0.0957). Neither age, CMV
      infection (viremia or a positive specimen from BAL), recipient's serology at the
      time of transplantation, or CMV disease was associated with BOS. None of these
      variables was associated with mortality on Cox regression analysis or univariate
      analysis. CONCLUSIONS: Administration of combination ganciclovir and hyperimmune
      globulin prophylactic therapy to lung transplant recipients at risk for CMV
      infection and disease is associated with a relatively low incidence of disease,
      which appears only after prophylaxis treatment with ganciclovir is completed.
      Ganciclovir prophylaxis does not prevent CMV viremia; however, viremia while on
      prophylaxis is not predictive of disease.

PMID- 9554628
TI  - Pulmonary tuberculosis treated with directly observed therapy: serial changes in
      lung structure and function.
AB  - OBJECTIVES: (1) To correlate structure (CT) with function in pulmonary
      tuberculosis (TB), and (2) to describe the evolution of structural and functional
      abnormalities when pulmonary TB is treated with directly observed therapy.
      SUBJECTS AND METHODS: Twenty-five patients with drug-susceptible pulmonary TB, 15
      cavitary and 10 noncavitary, were studied prospectively. Conventional CT and
      pulmonary function testing (spirometry, diffusing capacity, and arterial blood
      gases) were performed at baseline, and after 1 and 6 months of directly observed
      therapy. RESULTS: All but one patient with noncavitary miliary TB had CT evidence
      of endobronchial disease, and all patients with cavitary disease had coexistent
      reduced lung attenuation, the latter presumably a result of gas trapping, hypoxic
      vasoconstriction, and vascular injury. Functional impairment was minimal and in
      proportion to the number of diseased segments and cavitary volume. Bronchiectasis
      was significantly more likely to complicate cavitary than noncavitary disease (64
      vs 11%; p<0.05). CONCLUSIONS: CT findings correlate well with function in
      pulmonary TB. Physiologic data were consistent with the concept that pulmonary TB
      is an endobronchial disease that causes parallel reductions in ventilation and
      perfusion. This concurrent involvement of both airways and contiguous pulmonary
      blood supply offers an explanation for the minimal respiratory limitation
      experienced by these patients despite often extensive lung disease. Supervised
      therapy of drug-susceptible disease results in minimal structural and functional
      residua.

PMID- 9554629
TI  - Community respiratory viral infection in adult lung transplant recipients.
AB  - STUDY OBJECTIVE: To define the epidemiology, clinical manifestations, and long
      term complications of respiratory viral infections in adult lung transplant
      recipients. DESIGN: Retrospective review of the records of 122 adult lung
      transplant recipients over a 5-year period at one institution. RESULTS: Ten
      episodes of infection with respiratory syncytial virus, parainfluenza, influenza,
      or adenovirus were identified. All patients presented with symptoms of
      respiratory tract infection. Two patients died acutely and four patients
      subsequently had development of obliterative bronchiolitis (OB). CONCLUSIONS:
      These data suggest community respiratory viral infections cause significant
      morbidity and mortality in lung transplant recipients. Further prospective
      studies are warranted to clarify the relationship between respiratory viral
      infection and OB and to define the optimal therapy for these viral infections.

PMID- 9554630
TI  - A comparison of the availability of tobramycin for inhalation from vented vs
      unvented nebulizers.
AB  - STUDY OBJECTIVE: To compare drug output from a vented nebulizer (Pari LC Jet
      Plus) with a traditional unvented nebulizer (Hudson 1730 T Up-Draft 11) using
      aerosolized tobramycin, which is frequently used in the treatment of cystic
      fibrosis. DESIGN: Six nebulizers of each type were filled with a 4 mL tobramycin
      (80 mg) solution and were driven by a compressor (Pulmo-Aide). Various
      inspiratory flows (VI) (0, 5, 10, 15, 20 L/min for the Pari LC Jet Plus and 0, 5,
      and 10 L/min for the Hudson 1730, all at 40% relative humidity) were directed
      through each nebulizer. Drug output was measured from changes in weight and
      concentration (assessed by changes in osmometry) within the nebulizer. Particle
      size distributions were determined by laser diffraction allowing the calculation
      of the amount of aerosol output in the respirable range (<5 microm). The
      nebulizers were first run until end-nebulization to establish total drug output
      and then for either 4 or 5 min to determine the rate of drug output (mg/min)
      before intermittent aerosol output. RESULTS: The total drug output without VI for
      both the unvented and the vented nebulizers was not significantly different, 55
      (51, 60) mg for the Hudson 1730 vs 51 (49, 53) mg for the Pari LC Jet Plus (mean
      [95% confidence limits]). Inspiratory flow had no effect on the unvented Hudson
      1730 nebulizer but significantly increased the rate of total drug output and the
      rate of drug output in the respirable range for the vented Pari LC Jet Plus
      nebulizer (VI=0, 3.35 [2.84, 3.85] and 1.72 [1.48, 1.96] compared with VI=20,
      9.87 [9.03, 10.70] and 6.11 [5.33, 6.88] mg/min). CONCLUSIONS: These findings
      indicate that the increase in the rate of drug output with VI for the vented
      nebulizer would result in shorter nebulization times and a relative decrease in
      drug loss during the expiratory phase.

PMID- 9554631
TI  - Lung deposition of fenoterol and flunisolide delivered using a novel device for
      inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers
      with and without spacer devices.
AB  - STUDY OBJECTIVES: To compare lung deposition of fenoterol or flunisolide
      administered from a novel, multidose inhalation device delivering liquid droplets
      (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered
      dose inhalers (MDIs) with and without spacers. DESIGN: Two randomized, three-way
      crossover studies. SETTING: Clinical research laboratory. PARTICIPANTS: Healthy,
      nonsmoking volunteers. INTERVENTIONS: In one study, radiolabeled aerosols of
      fenoterol from the RESPIMAT device and from a conventional MDI with or without an
      Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second
      study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a
      RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and
      from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim,
      Germany). MEASUREMENTS AND RESULTS: Assessment of the deposition of fenoterol or
      flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was
      assessed based on reported adverse effects and spirometry (FEV1, FVC, and peak
      expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT
      device delivered significantly more fenoterol to the lungs than either an MDI
      alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose,
      respectively; p<0.01). Oropharyngeal deposition of fenoterol from the new device
      was lower than that from the MDI (37.1% vs 71.7%, respectively; p<0.01). The
      RESPIMAT device deposited significantly more flunisolide in the lungs compared
      with MDI plus spacer (44.6% vs 26.4%, respectively; p<0.01), while resulting in
      similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of
      a baffle into the RESPIMAT system reduced lung deposition of flunisolide to
      29.5%, and oropharyngeal deposition to 7.8% (p<0.01). CONCLUSION: The RESPIMAT
      device may prove to be an effective alternative to MDIs for the administration of
      inhaled bronchodilators and corticosteroids. The high lung deposition and low
      oropharyngeal deposition may lead to improved efficacy and tolerability of
      inhaled medications, especially corticosteroids.

PMID- 9554633
TI  - Compliance with peak expiratory flow monitoring in home management of asthma.
AB  - BACKGROUND: The recent consensus reports on asthma management emphasize the
      importance of using peak flowmeters to accurately assess the degree of airflow
      obstruction. However, the optimal way to use those devices has not yet been
      determined. OBJECTIVES: To assess compliance with peak expiratory flow (PEF)
      measurements in the long-term management of asthma, and identify the
      characteristics of patients with poor compliance. SETTING: Asthma clinics from
      three tertiary-care hospitals. DESIGN: A descriptive and prospective study of 1
      year duration. PATIENTS: Twenty-six patients with moderate to severe asthma
      taking part in an asthma education program. MAIN OUTCOME MEASURES: Patients were
      asked to measure morning and evening PEF using an electronic peak flowmeter with
      a 3-month memory; they were unaware that PEF values were being recorded by this
      device. RESULTS: Compliance with PEF measurements was relatively good during the
      first month (63% of the measurements done) but even with regular reinforcement,
      fell to 50% at 6 months and to 33% at 12 months. Right from the beginning, 8 of
      26 subjects (30%) never or almost never (<5% of the readings done) measured PEF,
      with seven of these subjects writing fabricated results in their diaries most of
      the time. At 12 months, 60% of the subjects were measuring PEF <25% of the time,
      and most of them continued writing fabricated PEF values in their diaries. None
      of the subjects' characteristics helped us to identify those who had poor
      compliance with these measurements. CONCLUSIONS: While short-term compliance with
      PEF measurements is fairly good, most patients with moderate to severe asthma are
      not interested in measuring PEF twice daily over a prolonged period. In the
      current management of asthma, PEF measurement devices can be suggested to those
      showing a strong personal interest in using them, but should be limited to short
      periods of time. Furthermore, this study outlines the usefulness of electronic
      peak flowmeters when doing clinical research where PEF improvement is an
      important outcome.

PMID- 9554632
TI  - Is normal bronchial responsiveness in asthmatics a reliable index for withdrawing
      inhaled corticosteroid treatment?
AB  - STUDY OBJECTIVE: Inhaled corticosteroid (ICS) treatment is first-line maintenance
      therapy in bronchial asthma. However, it is not clear whether and when ICS
      treatment can be withdrawn. The aim of this open study was to assess whether
      normalization of bronchial responsiveness could be used as a reliable index to
      assess the opportunity of ICS treatment withdrawal. DESIGN: Open study at two
      different points in time. SETTING: Outpatient pulmonary clinic. PATIENTS:
      Eighteen asthmatic subjects. MEASUREMENTS AND RESULTS: ICS therapy was withdrawn
      in subjects treated with beclomethasone dipropionate, at the maintenance dose of
      889+/-246 microg/d for >3 months. Upon recruitment, all subjects were
      asymptomatic, had FEV1 >70% of predicted value, and were in treatment with beta2
      agonists on an as-needed basis. Eight subjects (group 1) had normal bronchial
      responsiveness (methacholine provocative dose causing a 20% fall in FEV1 [PD20]
      >2,000 microg) and 10 subjects (group 2) had bronchial hyperresponsiveness (BHR)
      (PD20 < or = 2,000 microg). After withdrawal of ICS treatment, subjects were
      followed up for 3 weeks and were asked to record their asthma symptoms (cough,
      dyspnea, and wheezing) and their beta2-agonist use. At recruitment and at the end
      of follow-up, subjects underwent spirometry and a methacholine challenge test.
      Frequency of asthma exacerbation was similar in subjects with normal bronchial
      responsiveness (NBR) and in subjects with BHR (50% vs 60%), but subjects with NBR
      tended to remain asymptomatic for longer than those with BHR (mean+/-SD, 10.7+/
      4.4 days vs 5.5+/-3.8 days) (p=0.08). None of the subjects reported any condition
      that could have triggered exacerbation. Asthma exacerbation was associated with a
      significant decrease in FEV1 (-105+/-107 mL; p<0.05) and in PD20 (-1,332+/-1,020
      microg; p<0.001). CONCLUSIONS: Our study shows that the likelihood of asthma
      exacerbation is not reduced if ICS treatment is withdrawn when the subjects have
      NBR, but the exacerbation could be delayed. Further studies in larger populations
      of asthmatics are needed to confirm these findings.

PMID- 9554634
TI  - Longitudinal determinants of bronchial responsiveness to inhaled histamine.
AB  - BACKGROUND AND STUDY OBJECTIVE: The point prevalence of bronchial
      hyperresponsiveness (BHR) is imperfectly associated with current asthma, possibly
      due to changes over time in bronchial responsiveness (BR). To evaluate cross
      sectional and longitudinal determinants of BR, a population sample comprising 408
      children and adolescents, aged 7 to 17 years at enrollment, was examined twice, 6
      years apart. METHODS: Case history was obtained by interview and questionnaire.
      BR to inhaled histamine, pulmonary function, and skin prick test reactivity were
      measured using standard techniques. RESULTS: The point prevalence of BHR (the
      concentration of histamine causing a 20% decline in FEV1 <8 mg/mL) declined from
      childhood to early adulthood (25% and 6%, respectively; p<0.001); and similarly a
      decline in histamine dose-response slope was observed. At both surveys,
      prechallenge FEV1 percent predicted, asthma, and atopy, especially atopy to house
      dust mite (HDM), were important determinants for the degree of BR. After
      adjustment for prechallenge FEV1 percent predicted, no male-female difference was
      observed in degree of BR. Lower FEV1 percent predicted (p=0.003), asthma
      (p<0.001), higher degree of BR (p=0.003), and atopy to HDM (p=0.007) at
      enrollment predicted a higher degree of BR at the second survey (degree of BR at
      second survey adjusted for prechallenge FEV1). Furthermore, new asthma (p<0.001)
      and/or atopy to HDM (p=0.003) were associated with higher BR at the second
      survey. Confining the analysis to nonasthmatics showed that subjects with new or
      persistent atopy to HDM had significantly increased BR compared with nonatopic
      subjects; and, moreover, prechallenge FEV1 percent predicted was significantly
      correlated with BR. CONCLUSIONS: BR declines from childhood to early adulthood,
      possibly reflecting the increase in airway caliber. The level of FEV1 and atopy,
      especially to HDM, are important determinants for changes over time in level of
      BR, also in nonasthmatic subjects.

PMID- 9554635
TI  - The relation between multiple sleep latency test findings and the frequency of
      apneic events in REM and non-REM sleep.
AB  - STUDY OBJECTIVES: A recent study of 34 patients with mild obstructive sleep apnea
      syndrome (OSAS) suggested that the number of apneas and hypopneas per hour of
      sleep (apnea/hypopnea index [AHI]) may show a stronger correlation with
      sleepiness, as measured by the Multiple Sleep Latency Test (MSLT), when
      calculated for rapid eye movement (REM) sleep alone (AHIR) as opposed to the
      entire night. We sought to reexamine this possibility in a larger group of
      similar patients and in patients who had a wider range of OSAS severity. DESIGN:
      Retrospective and observational. SETTING: A large, accredited, academic sleep
      disorders center where a database of sleep study results is maintained. PATIENTS:
      We studied 1,146 persons who had polysomnography and MSLTs for clinical
      indications. RESULTS: In linear regression models, the AHI explained 11.0% of the
      variance in MSLT results, AHIN (AHI during non-REM sleep) explained 10.8%, and
      AHIR explained only 6.0% (p < or = 0.0001 for each). Among subjects with AHI <
      10, the AHI explained 3.1% of the variance (p=0.0012), the AHIN 2.3% (p=0.0049),
      and the AHIR 0.2% (p=0.40). Among all subjects, the ratio AHIR/AHIN had no
      influence on the overall relationship between AHI and sleepiness (p=0.23).
      CONCLUSIONS: We conclude that apneic events during REM and non-REM sleep probably
      contribute equally to sleepiness as measured by the MSLT.

PMID- 9554636
TI  - Arterial blood pressure response to transient arousals from NREM sleep in
      nonapneic snorers with sleep fragmentation.
AB  - STUDY OBJECTIVES: To assess the hemodynamic effects of graded arousals during
      nonrapid eye movement (NREM) sleep in patients with partial upper airway
      obstruction during sleep without obstructive sleep apnea/hypopnea, overnight beat
      to-beat BP was recorded in six patients. SETTING: At the end of each nonapneic
      obstructive event, EEG responses were graded as follows: grade 2, grade 1, and
      grade 0 were defined as increased high-frequency EEG lasting >15 s, 3 to 15 s,
      and no EEG arousals according to the American Sleep Disorders Association,
      respectively. MEASUREMENTS AND RESULTS: The following were observed during grade
      0, 1, and 2 EEG patterns (mean+/-SD): systolic pressure increased by 7.1+/-1.5,
      11.7+/-1.9, and 14.2+/-3.4 (p<0.005), respectively; diastolic pressure increased
      by 4.6+/-0.6, 6.7+/-1.7, and 9.4+/-3.0 (p<0.005), respectively; heart rate
      increased by 2.9+/-0.4, 3.9+/-2.2, and 8.6+/-4.6 (p<0.005), respectively.
      CONCLUSIONS: We conclude that nonapneic-nonhypopneic obstructive events are
      followed by arterial systemic pressure increases whose magnitude varies with the
      grade of the arousal.

PMID- 9554637
TI  - The efficacy of oral appliances in the treatment of persistent sleep apnea after
      uvulopalatopharyngoplasty.
AB  - Twenty-four patients who failed uvulopalatopharyngoplasty (UPPP) for obstructive
      sleep apnea (OSA) had an adjustable oral (Herbst) appliance made to treat the
      persistent apnea. Six patients discontinued the device prior to sleep evaluation.
      Eighteen patients had polysomnographic evaluations at baseline, post-UPPP, and
      with the Herbst appliance in place. The apnea-hypopnea index baseline (AHI) and
      arterial oxygen saturation (SaO2) nadir were 42.3+/-6.1 and 83.6+/-1.8%,
      respectively. There was no significant change in either parameter with surgery.
      With the oral appliance, the AHI fell to 15.3+/-4.4 (p < or = 0.01) and the SaO2
      nadir increased to 87.9+/-1.2% (p < or = 0.05). Ten of the patients had control
      of the OSA with the Herbst appliance with a fall in the AHI to < 10. There were,
      in addition, two partial responders as defined by an AHI of <20 and a >50% fall
      in AHI compared with baseline and post-UPPP values. All but one of the responders
      and partial responders had complete resolution of subjective symptoms of daytime
      sleepiness with the appliance. An adjustable oral appliance appears to be an
      effective mode of therapy to control OSA after an unsuccessful UPPP.

PMID- 9554638
TI  - Analysis of cell type and radiographic presentation as predictors of the clinical
      course of patients with bronchioalveolar cell carcinoma.
AB  - STUDY OBJECTIVES: Bronchioloalveolar carcinoma is a primary lung neoplasm of
      variable histopathologic, radiologic, and clinical expression. There are three
      cell types described in bronchioloalveolar carcinoma: Clara cells, mucin
      producing cells, and alveolar type II epithelial cells. It is unclear whether
      these three tumor cell types are associated with a specific radiologic
      presentation and clinical course. In this study, we investigated whether tumor
      cell type, identified by transmission electron microscopy, correlated with a
      specific radiologic pattern, and whether tumor cell type or radiologic
      presentation correlated with the patient's clinical course and outcome. DESIGN:
      Transmission electron microscopy was used to restudy tissue blocks from the
      original surgical histopathologic specimens in 54 patients with primary
      bronchioloalveolar carcinoma diagnosed over a 10-year period (1980 to 1990). The
      pretreatment radiographs were reviewed in each case, and the first chest
      radiograph obtained at the time of the discovery of the tumor in each patient was
      compared with the results of the ultrastructural study. The medical records of
      each patient were examined to obtain pertinent radiologic, clinical, and patient
      outcome information. MEASUREMENT AND RESULTS: There were 32 Clara cell tumors, 10
      mucin-producing cell tumors, and 1 alveolar type II epithelial cell tumor in this
      series. Eleven additional tumors had mixtures of two or more cell types. No
      statistically significant relationship was detected between tumor cell type and
      radiologic presentation or patient mortality pattern. There was increased
      mortality among patients who presented radiologically with segmental, lobar,
      multifocal, or diffuse disease compared with those patients exhibiting a solitary
      pulmonary nodule at presentation. CONCLUSION: Radiologic presentation, rather
      than tumor cell type, provides prognostic information that aids in predicting
      patient outcome.

PMID- 9554639
TI  - Thoracoscopic talc poudrage in malignant pleural effusions: effective pleurodesis
      despite low pleural pH.
AB  - STUDY OBJECTIVE: To determine the effectiveness of pleurodesis by thoracoscopic
      talc poudrage (TTP) in patients with low pH malignant pleural effusions. DESIGN:
      Review of prospectively collected data on all thoracoscopic procedures performed
      from 1982 to 1996. PATIENTS AND SETTING: Twenty-five members in a prepaid, closed
      panel health maintenance organization, whose malignant pleural effusion pH was <
      or = 7.30. INTERVENTIONS: Pleural fluid pH was measured prior to diagnostic and
      therapeutic, single puncture, rigid thoracoscopy, under local anesthesia, in an
      operating room. MEASUREMENTS AND RESULTS: Success of pleurodesis was determined
      with serial radiographs at 10 days, 30 days, and frequent intervals until death
      or up to 1 year following the procedure. Failure was indicated by evidence of
      recurrent fluid or persistence of a space between the visceral and parietal
      pleura. Morbidity of the procedure, days of chest tube drainage, and days of
      hospitalization were recorded concurrently during hospitalization and outpatient
      follow-up. Fifty of the 76 patients found to have a pleural pH measurement had a
      pleural pH >7.30, averaging 7.37 (7.31 to 7.55). The other 26 patients (34%) with
      pH < or = 7.30 (low pH) are the subjects of this study, of whom 25 were
      evaluable. Pleurodesis was successful in 22 of 25 (88%), although 4 died prior to
      30 days. The three failures all had trapped lung. Chest tube drainage averaged
      3.2+/-1.3 days, which approximated the time of hospitalization (3.3+/-1.1 days).
      There were no thoracoscopy-related deaths; significant morbidity occurred only in
      one patient with trapped lung, who had prolonged chest tube drainage before and
      after TTP, and eventually developed empyema. CONCLUSIONS: TTP is an effective
      pleurodesis technique in malignant pleural effusions, even when the pleural pH is
      low. The short hospital stay and high success rate make this approach a good
      choice in palliating symptomatic malignant pleural effusions.

PMID- 9554640
TI  - The acute effects of nasal positive pressure ventilation in patients with
      advanced cystic fibrosis.
AB  - OBJECTIVE: To evaluate the acute effects of noninvasive positive pressure
      ventilation (NPPV) in patients with stable chronic respiratory failure secondary
      to cystic fibrosis. PATIENTS: Eight patients (29+/-5 years of age) with severe
      airflow limitation (mean FEV1, 24+/-3% predicted) and chronic respiratory failure
      (PaO2=67+/-15 mm Hg and PaCO2=50+/-4 mm Hg) were evaluated. METHODS: Tidal
      volume, respiratory rate, minute ventilation, oxygen saturation, and
      transcutaneous CO2 (TcCO2) measurements were made over a 20-min period before and
      after the application of NPPV (inspiratory pressure of 10 to 12 cm H2O and
      expiratory pressure of 4 to 6 cm H2O). RESULTS: NPPV increased saturation from
      88+/-2% to 90+/-1% (p<0.05) and decreased TcCO2 from 51+/-3 mm Hg to 50+/-2 mm Hg
      (p<0.05). Tidal volume increased from 219+/-20 mL to 256+/-37 mL (p=not
      significant [NS]) and respiratory rate decreased from 24+/-2 to 18+/-1 (p<0.01).
      Minute ventilation decreased from 5.3+/-0.8 L/min to 4.6+/-0.6 L/min (p=0.08).
      There was no change in duty cycle (32+/-5% to 34+/-5%, p=NS). In two patients,
      esophageal pressure measurements were also recorded. There was a decrease in
      pressure from -21+/-1 cm H2O to -11+/-2 cm H2O and -14+/-1 cm H2O to -7+/-1 cm
      H2O. CONCLUSIONS: In patients with stable, severe cystic fibrosis, NPPV (1)
      acutely improves gas exchange, (2) decreases minute ventilation, suggesting
      either a reduction in CO2 production or an increase in alveolar ventilation, and
      (3) reduces work of breathing.

PMID- 9554641
TI  - Effect of high-frequency oral airway and chest wall oscillation and conventional
      chest physical therapy on expectoration in patients with stable cystic fibrosis.
AB  - STUDY OBJECTIVE: To compare the effect of high-frequency oral airway oscillation,
      high-frequency chest wall oscillation, and conventional chest physical therapy
      (CPT) on weight of expectorated sputum, pulmonary function, and oxygen saturation
      in outpatients with stable cystic fibrosis (CF). DESIGN: Prospective randomized
      trial. SETTING: Pediatric pulmonary division of a tertiary care center. PATIENTS:
      Fourteen outpatients with stable CF recruited from the CF center. INTERVENTIONS:
      Two modes of oral airway oscillation (1: frequency 8 Hz; inspiratory to
      expiratory [I:E] ratio 9:1; 2: frequency 14 Hz; I:E ratio 8:1), two modes of
      chest wall oscillation (1: frequency 3 Hz; I:E ratio 4:1; 2: frequency 16 Hz; I:E
      ratio 1:1, alternating with frequency 1.5 Hz, I:E ratio 6:1), and CPT (clapping,
      vibration, postural drainage, and encouraged coughing) were applied during the
      first 20 min of 4 consecutive hours. MEASUREMENTS AND RESULTS: Sputum was
      collected on an hourly basis for a total of 6 consecutive hours. During the first
      and the last hour, patients collected sputum without having any treatment and
      underwent pulmonary function tests (PFTs). Oxygen saturation was measured at 30
      min intervals during hours 1 to 6. For the first 20 min of the second to the
      fifth hour, patients received one of the treatments. To assess the effect of the
      intervention, the weight of expectorated sputum during hours 2 to 6 was averaged
      and expressed as percentage of the weight expectorated during the first hour
      (baseline). For the five treatment modalities, mean sputum dry and wet weights
      ranged between 122% and 185% of baseline. There was no statistically significant
      difference among the treatment modalities. As measured by sputum wet weight, all
      oscillatory devices tended to be less effective than CPT (p=0.15). As measured by
      dry weight, oral airway oscillation at 8 Hz with an I:E ratio of 9:1 and CPT
      tended to be more effective than the other treatment modalities (p=0.57). None of
      the treatment modalities had an effect on PFTs and oxygen saturation and all were
      well tolerated. CONCLUSION: In outpatients with stable CF, high-frequency
      oscillation applied via the airway opening or via the chest wall and CPT have
      comparable augmenting effects on expectorated sputum weight without changing PFTs
      or oxygen saturation. In contrast to CPT, high-frequency oral airway and chest
      wall oscillations are self-administered, thereby containing health-care expenses.

PMID- 9554642
TI  - Effects of positive end-expiratory pressure on oscillated flow rate during high
      frequency chest compression.
AB  - OBJECTIVE: To investigate the effects of positive end-expiratory pressure (PEEP)
      on end-expiratory lung volume (EELV) and mean oscillated flow rate (VOSC) during
      high-frequency chest compression (HFCC) in normal subjects and patients with
      severe COPD. DESIGN: Comparative study. SETTING: Pulmonary function and lung
      mechanics laboratory, University of Alberta Hospitals. PARTICIPANTS: Six normal
      subjects (five male; one female) and six patients with clinically stable COPD
      (five male; one female) with hypercapnia. INTERVENTIONS: A pneumatic vest system
      was operated at 10 Hz with a mean chest wall pressure of 16 cm H2O to provide the
      HFCC. A closed-circuit spirometer system permitted measurement of HFCC- and PEEP
      induced changes in EELV that were expressed as per cent baseline functional
      residual capacity (FRC). An isothermic chamber connected near the mouthpiece
      permitted measurement of VOSC. RESULTS: For the normal subjects, HFCC caused a
      significant decrease in EELV to 82.0% of FRC (p < or = 0.01) and the addition of
      4.8+/-0.5 cm H2O of PEEP during HFCC increased EELV to 97.5% FRC. In the COPD
      patients, HFCC decreased EELV to 92.3% of FRC (p < or = 0.01), and the addition
      of 3.7+/-1.0 cm H2O of PEEP increased EELV to 98.4% FRC. For the normal subjects,
      increasing EELV to near FRC caused VOSC during expiration to increase 14.6% (p <
      or = 0.01), but there was no significant effect on VOSC during inspiration (5.1%
      increase). In the COPD patients, PEEP increased VOSC during both inspiration
      (30.5%) and expiration (57.0%) (both, p < or = 0.01). CONCLUSIONS: Addition of a
      modest amount of PEEP during HFCC prevents the decrease in EELV and increases
      VOSC during both phases of spontaneous breathing in COPD patients. This higher
      VOSC during HFCC+PEEP may improve the effectiveness of HFCC in clearing mucus
      from the lungs of patients with airway disease.

PMID- 9554643
TI  - Absence of left-sided predominance in asbestos-related pleural plaques: a CT
      study.
AB  - STUDY OBJECTIVES: Differences between the number and areas of pleural plaques in
      every hemithorax could not be expected a priori. However, previous studies based
      on chest radiographs reported an unexplained left-sided predominance. In this
      paper, a comparison of summed surfaces and location of plaques calculated from CT
      studies was performed. PATIENTS AND METHODS: Thoracic CT scans from 40 adults
      with asbestos exposure and pleural plaques were analyzed. The surface area of
      every plaque was calculated, and summed areas were recorded separately for every
      hemithorax. The statistical analysis was performed with t-tests for paired
      samples. Emphasis was placed on measurement differences. MEASUREMENTS AND
      RESULTS: The results show lack of significant predominance for any hemithorax. A
      total of 668 plaques (352 right and 316 left) were measured, with an average area
      (+/-SD) of 47.81+/-47.72 cm2 for the right plaques and 45.34+/-67.32 cm2 for the
      left. The mean of differences (left minus right areas) was -2.56+/-53.68 and
      slightly statistically different from zero (p=0.652). CONCLUSIONS: Left-sided
      predominance of asbestos-related pleural plaques is not supported by this study.

PMID- 9554644
TI  - Transbronchial lung biopsy: can specimen quality be predicted at the time of
      biopsy?
AB  - STUDY OBJECTIVES: To determine the bronchoscopist's ability to predict specimen
      quality at the time of transbronchial biopsy and to determine the influence of
      biopsy specimen size and alveolar content on diagnostic value. DESIGN:
      Prospective, blinded, observational analysis. SETTING: Tertiary care academic
      hospital-based pulmonary practice. PATIENTS: Forty-three adult patients who
      underwent transbronchial lung biopsy. INTERVENTIONS: Each of 170 biopsy specimens
      was rated as to likelihood of containing diagnostic tissue, size and ability to
      float, tissue types present, number of alveoli, and pathologic diagnosis.
      RESULTS: Fifteen percent of biopsy specimens were small and 40% were large.
      Seventy-six percent of specimens floated; 61.8% of the 170 biopsy specimens
      contained abnormal lung tissue; and 14.7% of individual specimens were
      diagnostic. Fifty-two percent of specimens contained >20 alveoli. Larger biopsy
      specimens were more likely to contain diagnostic tissue (r=0.29, p=0.001). Cup
      forceps retrieved smaller pieces of tissue (p=0.007) and were less likely to
      obtain diagnostic tissue (p=0.06). Physician ratings of specimen quality (mean+/
      SD) did not differ between specimens containing normal and abnormal tissue
      (5.98+/-2.3 vs 5.46+/-5.5; p=0.24) or between specimens containing diagnostic vs
      nondiagnostic tissue (5.56+/-2.5 vs 6.25+/-2.1; p=0.14). Specimens that floated
      were no more likely to be diagnostic or abnormal than specimens that sank
      (p<0.05). Diagnosis when established was made by the first biopsy specimen in
      53.3% and the second in 33.3% CONCLUSIONS: Physician estimate of biopsy specimen
      quality and the float sign are not helpful in predicting that the biopsy specimen
      contains abnormal or diagnostic tissue. Diagnostic biopsy specimen will likely be
      obtained if the size of the specimen fills the forceps, 2 to 4 biopsies are
      performed, and toothed forceps are used.

PMID- 9554645
TI  - Use of a pulse oximeter in an adult emergency department: impact on the number of
      arterial blood gas analyses ordered.
AB  - STUDY OBJECTIVES: To assess the impact of pulse oximetry (SpO2) on the
      indications and the number of arterial blood gas (ABG) levels ordered in an adult
      emergency department (ED). DESIGN: A prospective study during a 2-month period in
      1993 with a pulse oximeter available and a comparison with the same period in
      1992 without the oximeter. SETTING: An adult medical ED of a university hospital
      in France. PATIENTS: All patients who underwent ABG or SpO2 measurements.
      INTERVENTIONS: During the prospective study, residents ordered ABG or SpO2
      measurements at their discretion. The reasons for their ordering were reviewed by
      two independent experts who determined whether their choice was justified. The
      data were compared with those for 184 consecutive patients who had ABG
      measurements in 1992. MEASUREMENTS AND RESULTS: The study included 152 patients.
      SpO2 alone was used in 33 patients; ABG levels were measured in 119 patients. The
      use of SpO2 did not result in the ordering of fewer useful ABG determinations.
      One hundred and five (88%) ABG measurements were justified. There were fewer
      unjustified ABG determinations in 1993 when the pulse oximeter was available than
      in 1992 when it was not (14 of 119 vs 54 of 184; p<0.001) mainly because fewer
      ABG determinations were ordered for miscellaneous nonrespiratory indications (13
      of 119 vs 43 of 184; p<0.01). CONCLUSION: The availability of a pulse oximeter
      did not affect the ordering of useful ABG measurements but allowed a significant
      reduction of unjustified ABG measurements. Substantial cost savings could be
      achieved by using SpO2 in an ED.

PMID- 9554646
TI  - Right ventricular end-diastolic volume as a predictor of the hemodynamic response
      to a fluid challenge.
AB  - OBJECTIVE: To compare thermodilution right ventricular end-diastolic volume index
      (RVEDVI) and pulmonary artery occlusion pressure (Ppao) as predictors of the
      hemodynamic response to a fluid challenge. DESIGN: Prospective cohort study.
      SETTING: Medical ICU of a university-affiliated county hospital and medical
      surgical ICU of a community hospital. PATIENTS: Twenty-five critically ill
      patients who had one or more clinical conditions that suggested the possibility
      of inadequate preload. INTERVENTIONS: Thirty-six fluid challenges. Fluid (saline
      or colloid) was administered rapidly until the Ppao rose by at least 3 mm Hg.
      When a patient underwent more than one fluid challenge, these were given on
      separate days and for different clinical indications. MEASUREMENTS AND RESULTS:
      Responders (n=20; > or = 10% increase in stroke volume [SV]) and nonresponders
      (n=16; <10% increase in SV) differed with respect to baseline Ppao (10.0+/-3.4 vs
      14.2+/-3.6 mm Hg; p=0.001), but not with respect to baseline RVEDVI (105+/-31 vs
      119+/-33 mL/m2; p=0.22). There was a moderate correlation between RVEDVI and
      fluid-induced change in SV (r=0.44); the relationship between Ppao and change in
      SV was stronger (r=0.58). A positive response to fluid was observed in 4 of 9
      cases in which RVEDVI exceeded 138 mL/m2, a threshold value that has been
      suggested to reliably predict a poor response to fluid. CONCLUSION: RVEDVI was
      not a reliable predictor of the response to fluid. As a predictor of fluid
      responsiveness, Ppao was superior to RVEDVI. In an individual patient, adequacy
      of preload is best assessed by an empiric fluid challenge.

PMID- 9554647
TI  - Serum cardiac troponin T as a prognostic marker in early sepsis.
AB  - STUDY OBJECTIVE: Sepsis is the leading cause of death in the noncardiologic ICU.
      Maldistributed nutritive blood flow and altered convective and diffusive oxygen
      transport during sepsis can lead to organ dysfunction and multiple organ failure.
      One of the causes of myocardial dysfunction is thought to be myocardial ischemia
      in sepsis; however, conventional biochemical parameters to detect myocardial
      ischemia lack sensitivity and specificity. Serum cardiac troponin T (S-TnT) was
      reported to have higher sensitivity and specificity in diagnosing minor
      myocardial injury. The aim of this study was to investigate if and how often S
      TnT is pathologically elevated in patients with sepsis and to evaluate whether S
      TnT might be a prognostic marker in early sepsis. DESIGN: Prospective study.
      SETTING: Surgical ICU. PATIENTS: Twenty-six patients with sepsis were included in
      this study within 24 h of the onset of sepsis. The patients were allocated a
      priori to a high S-TnT group (S-TnT > or = 0.2 microg/L) and a low S-TnT group (S
      TnT<0.2 microg/L). MEASUREMENT: Blood samples for the determination of S-TnT and
      conventional myocardial ischemia markers as well as for adhesion molecules were
      drawn. Hemodynamic measurements were performed every 4 h during the first 24 h
      and then once per day over 7 days. S-TnT was determined by enzyme-linked
      immunosorbent sandwich assay. RESULTS: Eighteen patients had pathologically high
      S-TnT values. High S-TnT values were associated with an increased mortality rate
      (15/18 in the high S-TnT group vs 3/8 in the low S-TnT group; p=0.02).
      Significant differences between the two groups were found in the norepinephrine
      dosages at maximum values of S-TnT. Soluble intercellular adhesion molecule-1 was
      significantly elevated in the high S-TnT group. CONCLUSIONS: As high S-TnT values
      were associated with an increased mortality rate, it seems reasonable to further
      evaluate S-TnT as a prognostic marker of myocardial ischemia in patients with
      sepsis under different therapeutic regimens.

PMID- 9554648
TI  - Failure of splanchnic resuscitation in the acutely injured trauma patient
      correlates with multiple organ system failure and length of stay in the ICU.
AB  - INTRODUCTION: The purpose of our study was to evaluate the relationship between
      the state of splanchnic perfusion and morbidity and mortality in the
      hemodynamically unstable trauma patient acutely resuscitated in the ICU. METHODS:
      Gastric intramucosal pH (pHi) was monitored in a blinded fashion in 19
      consecutive critically ill trauma patients with evidence of systemic
      hypoperfusion (arterial pH [pHa] <7.35, base excess >2.3 mmol/L, lactic acid >2.3
      mEq/L) who received right heart catheters to guide resuscitation and subsequent
      hemodynamic monitoring. DESIGN: Prospective randomized consecutive series with
      retrospective analysis of data. SETTING: University hospital, surgical ICU.
      RESULTS: The mean values of APACHE II (acute physiology and chronic health
      evaluation) Injury Severity Score, pHa, arterial base excess, cardiac index,
      oxygen delivery index, and oxygen consumption index by 24 h were similar
      (Student's t test, p>0.1) between survivors and nonsurvivors and between those
      who developed at most a single (SOF) vs multiple organ system failure (MOSF).
      Supranormal oxygen delivery and utilization parameters were evenly distributed
      among survivors and nonsurvivors and patients with SOF and MOSF (chi2, p>0.5).
      Ten patients had a pHi <7.32 and nine patients had a pHi > or = 7.32 by 24 h.
      Fifty percent of patients with a pHi <7.32 died, compared with 11% of patients
      with a pH > or = 7.32 (chi2, p=0.07). Sixty percent of patients with a pHi <7.32
      developed MOSF compared with 11% of patients with a pHi > or = 7.32 (chi2,
      p=0.03). The one patient who developed MOSF and died in the pHi > or = 7.32
      cohort suffered from massive head trauma and had all futile medical interventions
      halted. No other patients who achieved a pH > or = 7.32 by hour 24 developed
      MOSF. Survivors with a pHi <7.32 at hour 24 had an increased ICU stay (pHi
      <7.32=46+/-15 days, pHi > or = 7.32=13+/-9 days; p<0.01). A pHi <7.32 carried a
      relative risk of 4.5 for death and 5.4 for the occurrence of MOSF. CONCLUSION:
      Attainment of a pHi > or = 7.32 at hour 24 carried a significantly reduced
      likelihood of MOSF. Being an inference of the state of regional perfusion, in a
      high-risk microvascular bed, gastric intraluminal tonometry should identify
      perfusion states of compensated or uncompensated shock during hemodynamic
      resuscitation of the critically ill injury patient. A low pHi appears to be a
      marker of postresuscitative morbidity and subsequent increased length of stay.

PMID- 9554649
TI  - Reproducibility of double indicator dilution measurements of intrathoracic blood
      volume compartments, extravascular lung water, and liver function.
AB  - STUDY OBJECTIVE: Arterial thermal dye dilution (TDDart) with the COLD system
      (Munich, Germany) allows measurement of cardiac index (CI), partial blood
      volumes, lung water, and liver function. The aim of the study was to determine
      agreement of TDDart measurements with pulmonary artery thermal dilution
      measurements (TDpa) and to assess the reproducibility of TDDart parameters.
      DESIGN: Prospective study. SETTING: ICU of a university hospital department of
      cardiac surgery. PATIENTS: Thirty consecutive patients after coronary artery
      bypass grafting. MEASUREMENTS AND RESULTS: Triplicate measurements of TDDart
      parameters were performed 1, 3, 6, 12, and 24 h postoperatively and coefficients
      of variation (CVs) were computed. At the 3-h point, additional fivefold TDDart
      measurements were done and compared with TDpa measurements. The coefficient of
      correlation for CI from TDDart vs TDpa was 0.96 (p<0.001), and the mean
      difference was 0.16 L/min/m2 (2.4%). The CVs of the TDDart and TDpa CI
      measurement were 7.2% and 5.9%; the CVs of other TDDart parameters were 4.6%
      (cardiac function index), 8.3% (global end-diastolic volume), 7.0% (intrathoracic
      blood volume), 7.6% (total blood volume), 7.4% (right ventricular end-diastolic
      volume), 7.4% (right heart end-diastolic volume), 11.3% (left heart end-diastolic
      volume [LHEDV]), 12.0% (right to left heart volume proportion [R/LHV]), 8.8%
      (pulmonary blood volume), 10.8% (extravascular lung water), 16.4% (plasma
      disappearance rate of dye), and 19.8% (dye clearance). The CV did not depend on
      Glasgow coma scale or on body temperature. CONCLUSION: The CVs of LHEDV and R/LHV
      are influenced by asynchronous TDDart and TDpa variation. The CVs of plasma
      disappearance and dye clearance are increased as the half-life of the dye is
      longer than the measurement sequence. All other parameters derived from TDDart
      and TDpa show a clinically sufficient reproducibility.

PMID- 9554650
TI  - Gastric and esophageal intramucosal PCO2 (PiCO2) during endotoxemia: assessment
      of raw PiCO2 and PCO2 gradients as indicators of hypoperfusion in a canine model
      of septic shock.
AB  - STUDY OBJECTIVES: To validate capnometric recirculating gas tonometry (CRGT) for
      continuously monitoring gut intramucosal PCO2 (PiCO2) in a septic shock model,
      and to compare gastric vs esophageal PCO2 vs intramucosal-arterial PCO2
      gradients. INTERVENTIONS: CRTG catheters were placed in the stomach and esophagus
      of six anesthetized dogs. A saline solution filled balloon tonometry (ST)
      catheter was also placed in the stomach. After equilibration, 3 mg/kg Escherichia
      coli lipopolysaccharide (LPS) was administered IV. PiCO2 measurements were made
      at 0, 45, and 90 min post-LPS by ST and continuously by CRGT. RESULTS: Baseline
      PiCO2 was 41.5+/-1.9 (+/-SE) in the stomach by CRGT, 38.0+/-1.0 by ST, and 43.0+/
      4.4 mm Hg in the esophagus (p=not significant). Gastric PiCO2 by CRGT increased
      to 47.0+/-2.4 mm Hg by 25 min post-LPS (p<0.05), whereas gastric (ST) and
      esophageal PiCO2 increased significantly by 45 min post-LPS. Good agreement was
      observed between gastric CRGT and ST measurements (mean bias, 1.3 mm Hg). The
      PiCO2-PaCO2 gradient increased post-LPS, but was significant only for gastric
      CRGT measurements 90 min post-LPS infusion. CONCLUSION: CRGT provided continuous
      gastric PiCO2 measurements that were in close agreement with ST but detected
      changes earlier than the conventional technique. Continuous esophageal PiCO2
      represents a valid alternative for assessing gastric PiCO2.

PMID- 9554651
TI  - Optimizing standard cardiopulmonary resuscitation with an inspiratory impedance
      threshold valve.
AB  - OBJECTIVES: This study was designed to assess whether intermittent impedance of
      inspiratory gas exchange improves the efficiency of standard cardiopulmonary
      resuscitation (CPR). BACKGROUND: Standard CPR relies on the natural elastic
      recoil of the chest to transiently decrease intrathoracic pressures and thereby
      promote venous blood return to the heart. To further enhance the negative
      intrathoracic pressures during the "relaxation" phase of CPR, we tested the
      hypothesis that intermittent impedance to inspiratory gases during standard CPR
      increases coronary perfusion pressures and vital organ perfusion. METHODS: CPR
      was performed with a pneumatically driven automated device in a porcine model of
      ventricular fibrillation. Eight pigs were randomized to initially receive
      standard CPR alone, while seven pigs initially received standard CPR plus
      intermittent impedance to inspiratory gas exchange with a threshold valve set to 
      40 cm H2O. The compression:ventilation ratio was 5:1 and the compression rate was
      80/min. At 7-min intervals the impedance threshold valve (ITV) was either added
      or removed from the ventilation circuit such that during the 28 min of CPR, each
      animal received two 7-min periods of CPR with the ITV and two 7-min periods
      without the valve. RESULTS: Vital organ blood flow was significantly higher
      during CPR performed with the ITV than during CPR performed without the valve.
      Total left ventricular blood flow (mean+/-SEM) (mL/min/g) was 0.32+/-0.04 vs
      0.23+/-0.03 without the ITV (p<0.05). Cerebral blood flow (mL/min/g) was 20%
      higher with the ITV (+ITV, 0.23+/-0.02; -ITV, 0.19+/-0.02; p<0.05). Each time the
      ITV was removed, there was a statistically significant decrease in the vital
      organ blood flow and coronary perfusion pressure. CONCLUSIONS: Intermittent
      impedance to inspiratory flow of respiratory gases during standard CPR
      significantly improves CPR efficiency during ventricular fibrillation. These
      studies underscore the importance of lowering intrathoracic pressures during the
      relaxation phase of CPR.

PMID- 9554652
TI  - Microsatellite instability and loss of heterozygosity at chromosomes 9 and 17 in
      non-small cell lung cancer.
AB  - BACKGROUND: Microsatellite instability (MI) and loss of heterozygosity (LOH) are
      described in lung cancer specimens. However, their importance in tumorigenesis
      remains unknown. The aim of this study was to identify the presence of MI and LOH
      in human tumor and normal bronchial mucosa DNA. METHODS: We performed biopsies
      with fiberoptic bronchoscopy and took specimens from the tumor and from the
      opposite site normal bronchial mucosa in 20 patients with non-small-cell lung
      cancer (NSCLC). Four patients had an adenocarcinoma, while 16 had a squamous cell
      carcinoma. Also, 6 patients had an early-stage disease (stages I and II), while
      14 patients had an advanced-stage disease (stages III and IV). All paired
      specimens were studied for MI and LOH on chromosome 17p, 17q, 9p, and 9q, with 10
      polymorphic markers. RESULTS: Sixteen of 20 tumors displayed genetic alterations
      (80%). Six tumors (30%) exhibited MI, five tumors (25%) exhibited LOH, while five
      tumors exhibited MI and LOH concurrently. The marker HBX had the most frequent
      incidence of LOH (4/20, 20%), indicating that the hbx gene becomes a strong
      candidate tumor suppressor gene, whereas of MI it was D17S515 (4/20, 20%). No
      relationship was observed between the presence of LOH or MI and the histologic
      subtype of NSCLC or the stage of the disease. CONCLUSION: Results suggest that
      genetic alterations exist in tumor, compared with the normal mucosa DNA. They may
      have a role in carcinogenesis as they exist in all stages and in both NSCLC
      histologic subtypes studied.

PMID- 9554653
TI  - Long-acting inhaled beta2-agonists in asthma therapy.
AB  - OBJECTIVE: To review the pharmacology of the long-acting inhaled beta2-agonists,
      salmeterol and formoterol, summarize results of their clinical trials, evaluate
      their safety records, and discuss their roles in the treatment of asthma. DATA
      SOURCES: Preclinical and clinical studies involving salmeterol or formoterol were
      identified by a MEDLINE search, weekly computerized literature updates, and
      manual searches. Studies of satisfactory quality were chosen for review. DATA
      SYNTHESIS: Salmeterol and formoterol are potent and selective beta2-adrenoceptor
      agonists with durations of action >12 h. Their major differences are that
      formoterol has a rapid onset of action and is a partial agonist of high intrinsic
      efficacy, whereas salmeterol has a delayed onset and is a partial agonist of low
      intrinsic efficacy. Twice daily use of either drug results in improved lung
      function, reduced symptoms, and a better quality of life. These agents protect
      against exercise-induced asthma for 12 h and eliminate nighttime awakening in
      most patients. Limited tolerance develops, especially to their bronchoprotective
      effects, but their improvement of lung function is sustained. CONCLUSIONS:
      Regular use of salmeterol or formoterol provides subjective and objective
      amelioration of asthma in patients experiencing excessive symptoms or physiologic
      impairment despite the regular administration of low doses of inhaled
      corticosteroids (equivalent to approximately 500 microg/d of beclomethasone).
      Intermittent use of either long-acting beta2-agonist can provide prolonged
      protection against exercise-induced asthma or nighttime symptoms. Patients should
      be instructed to continue taking inhaled steroids when long-acting beta2-agonists
      are administered on a regular schedule and to not take long-acting beta2-agonists
      between regularly scheduled doses. Used properly, they are effective and safe
      adjunctive agents in the treatment of asthma.

PMID- 9554654
TI  - The natural history and rate of progression of aortic stenosis.
AB  - One of the challenges in clinical cardiology is to determine the optimal time of
      valve replacement surgery in patients with aortic stenosis. To meet this
      challenge, one requires an accurate knowledge of the natural history and rate of
      progression of the disease. This review will summarize the natural history of
      aortic stenosis in terms of symptoms, mortality, and stenosis progression.

PMID- 9554655
TI  - Controversies surrounding long-term anticoagulation of very elderly patients in
      atrial fibrillation.

PMID- 9554656
TI  - Ischemic heart disease with congestive heart failure--problems in clinical
      management.

PMID- 9554657
TI  - A man with dyspnea, productive cough, and chest radiograph showing hyperinflation
      and a diffuse nodular pattern.

PMID- 9554658
TI  - Hypoxic respiratory failure in a 30-year-old spelunker.

PMID- 9554659
TI  - Acute pneumopathy in a nonsurgical transsexual.

PMID- 9554660
TI  - Massive hemoptysis from a pulmonary artery aneurysm associated with an
      emphysematous bulla.
AB  - A 66-year-old man with a history of COPD and Aspergillus fumigatus infection
      developed massive hemoptysis. Pulmonary artery angiography revealed an aneurysm
      which was successfully treated with coil embolization. This is the first known
      report of a pulmonary artery aneurysm causing massive hemoptysis in a patient
      with bullous emphysema.

PMID- 9554661
TI  - Venous and arterial gas embolism associated with positive pressure ventilation.
AB  - We report a 53-year-old woman with ARDS who required positive pressure
      ventilation with positive end-expiratory pressure. She sustained an acute right
      ventricular myocardial infarction associated with cardiovascular instability. The
      next day she sustained a fatal cerebral arterial gas embolism. Intravascular gas
      was documented within the cerebral, coronary, and pulmonary arterial
      circulations. Clinicians need to be aware of venous and arterial gas embolism as
      a complication of mechanical ventilation.

PMID- 9554662
TI  - Elevation of peak expiratory flow by a "spitting" maneuver: measured with five
      peak flowmeters.
AB  - STUDY OBJECTIVE: To determine if peak expiratory flow (PEF) is higher using
      incorrect technique versus correct technique with five marketed peak flowmeters.
      DESIGN: Randomized, nonblinded study. SETTING: University pulmonary medicine
      clinic. PATIENTS: Twenty adults with clinically stable asthma. INTERVENTIONS:
      After inhaling 2 puffs of albuterol via a valved aerosol holding chamber
      (Aerochamber), patients were instructed over the next 15 min in correct and
      incorrect (a "spitting" action) technique when using peak flowmeters. Order of
      use of five peak flowmeters and correct vs incorrect technique was random.
      MEASUREMENTS AND RESULTS: PEF (percentage of personal best) was recorded for best
      of three attempts with correct and incorrect technique. Each peak flowmeter had a
      statistically significant elevation in PEF with incorrect technique. The range
      for elevation in PEF using incorrect technique was 12.4 to 68.2% above the PEF
      with the subject using correct technique. CONCLUSION: Each of the five marketed
      peak flowmeters had a significant elevation in PEF when a "spitting action" was
      used. Clinicians need to instruct patients carefully regarding correct technique
      when using peak flowmeters.

PMID- 9554663
TI  - ARDS and adrenal insufficiency associated with the antiphospholipid antibody
      syndrome.
AB  - The antiphospholipid antibody syndrome (APS) is typically characterized by
      recurrent arterial and/or venous thromboses, miscarriages, and thrombocytopenia.
      There have been five reported cases of ARDS associated with primary APS. Adrenal
      insufficiency has also been reported as a rare complication of APS. We report a
      case of both ARDS and adrenal insufficiency associated with primary APS. Chest
      radiographs and pulmonary angiography studies revealed findings consistent with
      ARDS. CT scans confirmed the presence of bilateral adrenal hemorrhagic
      infarction. Patients with APS are at an increased risk of widespread vascular
      thrombosis due to the presence of circulating antiphospholipid antibodies. This
      case emphasizes the importance of recognizing APS and its potential for multiple
      organ system involvement.

PMID- 9554664
TI  - Circumflex coronary artery dissection following waterskiing.
AB  - A previously healthy 35-year-old woman experienced chest discomfort following
      mild blunt chest trauma while waterskiing. During the following 48 h, she
      underwent evaluation in two separate emergency departments (EDs) where she was
      found to have normal ECGs and cardiac enzyme values. She was subsequently
      discharged from both EDs. Twelve hours after the second ED visit, she was
      discovered unconscious at home and was resuscitated from ventricular
      fibrillation. Emergency cardiac catheterization demonstrated moderate circumflex
      disease without angiographic evidence of a false lumen or intimal flap. Left
      ventriculography demonstrated posterolateral wall hypokinesis. Eight days after
      remaining ventilator-dependent and unconscious, the patient was declared brain
      dead. At autopsy, the patient was found to have a dissection of the circumflex
      artery. Waterskiing is an unusual source of cardiac trauma; however, we believe
      this to be the first reported case of dissection in the circumflex artery
      following blunt chest trauma.

PMID- 9554665
TI  - Board review courses for critical care medicine.

PMID- 9554666
TI  - Deciphering histoplasmosis, systemic noncaseating granuloma, and sarcoidosis in
      the literature.

PMID- 9554667
TI  - False-positive results of carcinoembryonic antigen in pleural effusions.

PMID- 9554668
TI  - Tumor markers in sputum of patients with bronchioloalveolar carcinoma.

PMID- 9554669
TI  - Intracavitary bleomycin vs interferon in the management of malignant pleural
      effusions.

PMID- 9554670
TI  - A case of systemic lupus erythematosus or hepatitis C virus?

PMID- 9554671
TI  - Health-related quality of life: what is being measured?

PMID- 9554672
TI  - Exercise testing in patients with interstitial lung disease.

PMID- 9554673
TI  - Where have all the flowers gone: where is the joy in medicine?

PMID- 9554674
TI  - Case of the month: Complications of therapy, nursing homes, and the elderly.
      Autopsy Committee of the College of American Pathologists.

PMID- 9554675
TI  - Lifestyle, stress, and genes in peptic ulcer disease: a nationwide twin cohort
      study.
AB  - BACKGROUND: The familial accumulation of peptic ulcer disease observed in several
      studies may be attributable to genetic effects, aggregation of environmental
      exposure (shared environment), or both. The intrafamilial spread of Helicobacter
      pylori infection has raised the question whether shared environment could explain
      the familial aggregation of peptic ulcer disease rather than genetic similarity
      of family members. OBJECTIVE: To examine the contribution of genetic and
      environmental factors to the pathogenesis of peptic ulcer disease in a nationwide
      population-based cohort of adult twins. METHODS: The Finnish Twin Cohort consists
      of all same-sexed twin pairs born before 1958 with both twins alive in 1975. The
      total number of twin pairs is 13888, of whom 4307 are monozygotic (MZ) and 9581
      are dizygotic (DZ) twins. Questionnaire surveys of twins were carried out in
      1975, 1981, and 1990, including medical and psychosocial questions. One question
      asked whether a physician had ever made a diagnosis of gastric or duodenal ulcer.
      In addition, hospital discharge data from 1972 to 1991 were linked with the twin
      cohort to obtain those twin individuals who had been treated for gastric or
      duodenal ulcer. The prevalence of and concordance for peptic ulcer disease were
      examined in MZ and DZ twins. Model-fitting analysis was used to specify the
      relative roles of genetic and environmental factors. The contribution of
      lifestyle factors and stress was examined prospectively in an incidence study and
      by comparison of discordant pairs. RESULTS: The prevalence of peptic ulcer
      disease was 6.2% in men and 2.8% in women in 1975. There were 63 MZ and 86 DZ
      pairs concordant for peptic ulcer disease. Concordance for disease was
      significantly higher in MZ than in DZ twin pairs; the probandwise concordance
      rate was 23.6% (95% confidence interval [CI], 20.9%-26.3%) in MZ twins and 14.8%
      (95% CI, 13.3%-16.3%) in DZ twins. In the model-fitting analysis, a model with
      both additive genetic and unshared environmental effects had the best goodness-of
      fit. Thirty-nine percent (95% CI, 32%-47%) of the liability to peptic ulcer
      disease was explained by genetic factors and 61% (95% CI, 53%-68%) by individual
      environmental factors. In the incidence study (logistic regression analysis of
      the entire cohort initially free of peptic ulcer disease, with subjects diagnosed
      as having peptic ulcer after 1975 as cases), current smoking (relative risk, 2.2;
      95% CI, 1.5-3.2) and high stress levels (relative risk, 3.2; 95% CI, 1.4-7.6) in
      men and regular use of analgesics (relative risk, 3.3; 95% CI, 1.3-8.1) in women
      predicted peptic ulcer disease during the follow-up from 1976 to 1991. In the
      analysis of discordant pairs, smoking in men and regular use of analgesics in
      both sexes were predictors of peptic ulcer disease. CONCLUSIONS: The
      questionnaire and hospital usage data on peptic ulcer disease in the population
      based twin cohort suggest that the familial aggregation of the disease is modest,
      and attributable almost solely to genetic factors. Environmental effects not
      shared by family members were significant predictors of disease, and they were
      attributable to smoking and stress in men and the use of analgesics in women. The
      minor effects of shared environment to disease liability do not support the
      concept that the clustering of risk factors, such as H pylori infection, would
      explain the familial accumulation of peptic ulcer disease.

PMID- 9554676
TI  - Effectiveness of treatments of depression in older ambulatory patients.
AB  - OBJECTIVE: To determine the effectiveness of acute-phase pharmacological and
      psychological treatments of depression in older ambulatory patients by
      systematically reviewing original research relevant to this topic. METHODS:
      Searches in MEDLINE and PsycINFO and manual reviews of bibliographies located 233
      articles. Of these, 40 (37 different studies) met our 8 inclusion criteria:
      original research, written in English or French, subjects 55 years and older,
      diagnosis of depression, outpatient or community setting, prospective controlled
      study design, acute-phase pharmacological or psychological treatment, and outcome
      measure of depression. Two independent reviewers assessed the methodological
      quality of each article using a standard form and a quality score was computed.
      Quantitative data on levels of depression at the end of treatment were
      abstracted. Results were grouped by specific treatment comparison (type of
      treatment and type of control group). For comparisons that used the Hamilton
      Depression Rating Scale, we computed mean posttreatment differences. Effect sizes
      were computed from the Hamilton Depression Rating Scale or an alternative scale.
      RESULTS: In studies that compared active drugs with placebo, the heterocyclic
      drugs significantly reduced the posttreatment Hamilton Depression Rating Scale
      score (mean difference, -5.78; 95% confidence interval, -8.31 to -3.25); other
      drugs had smaller effects. In studies that compared active drugs, there were no
      significant differences overall between different classes of drugs; selective
      serotonin reuptake inhibitors appeared to be as effective as heterocyclic drugs.
      Rational psychological treatments performed significantly better than no
      treatment (mean posttreatment Hamilton Depression Rating Scale difference, -7.25;
      95% confidence interval, -10.10 to -4.40) but not significantly better than that
      for controls who received similar attention. Adjustment for the study quality
      score did not affect these results. CONCLUSIONS: Based on comparisons with
      untreated controls, heterocyclic antidepressants and rational psychological
      therapies appear to be the most effective treatments for older ambulatory
      patients with mild to moderate depression. Based on drug-drug comparisons,
      selective serotonin reuptake inhibitors appear to be as effective as heterocyclic
      drugs. However, overall, the magnitude of the treatment effects is modest.
      Limitations in the quantity and quality of appropriate studies suggest a sober
      approach to treatment in this population.

PMID- 9554677
TI  - Accuracy of an automated blood pressure device in stable inpatients: optimum vs
      routine use.
AB  - BACKGROUND: Despite widespread use of the automated blood pressure (BP) device
      (IVAC model 4200, IVAC Corporation, San Diego, Calif), there is little formal
      validation in the literature on its accuracy. OBJECTIVE: To assess the accuracy
      of the IVAC 4200 device, both under standardized conditions and as routinely used
      by ward staff, compared with the true indirect BP measured by mercury manometer
      (MM). METHODS: One hundred forty-five stable inpatients were randomly selected
      for BP measurements by 3 randomly ordered protocols: (1) MM performed by
      certified investigators, (2) IVAC 4200 BP performed by trained investigators
      (research automated [RA]), and (3) IVAC 4200 BP performed by ward personnel (ward
      automated [WA]). RESULTS: For RA compared with MM ("true" indirect BP), 59% of
      systolic and 54% of diastolic readings were within 5 mm Hg and 83% of systolic
      and 86% of diastolic were within 10 mm Hg for a British Hypertension Society
      grade C for both. For WA compared with MM, 40% of systolic and 50% of diastolic
      readings were within 5 mm Hg and 70% of systolic and 80% of diastolic readings
      were within 10 mm Hg for British Hypertension Society grades D and C,
      respectively. The presence of arrhythmias and/or low K5 values (fifth phase of
      Korotkoff sounds <30 mm Hg) significantly increased the inaccuracy for diastolic
      values. Inappropriate cuff selection significantly increased inaccuracy of
      systolic BP (WA vs MM). CONCLUSIONS: The IVAC 4200 yields substandard estimates
      of systolic and diastolic BP even under standardized, thus optimum conditions.
      The presence of arrhythmias or low K5 values and the selection of inappropriate
      cuff size by the ward staff also contributed to inaccuracy.

PMID- 9554678
TI  - Most common dermatologic problems identified by internists, 1990-1994.
AB  - BACKGROUND: Internists in all settings see many patients with skin conditions.
      Thus, their education in dermatology is important. Information on which areas of
      dermatology are most commonly seen in internal medicine practices is necessary
      for designing effective educational programs on skin disease. OBJECTIVE: To
      determine what types of dermatologic problems internists most commonly diagnose.
      METHODS: National Ambulatory Medical Care Survey data from 1990 to 1994 were
      analyzed for dermatologic diagnoses. Physicians specializing in internal medicine
      and all its subspecialties were compared with dermatologists and with other
      physicians. RESULTS: The most common skin disorders diagnosed by internists were
      dermatitis (15.8% of all diagnoses) and bacterial skin infections (14.0% of all
      diagnoses). Combined, bacterial, fungal, and viral infections included 28.3% of
      the most common dermatologic diagnoses made by internists. The top 10 most common
      diagnoses accounted for 57.9% of all skin-related diagnoses and the top 20 most
      common diagnoses accounted for 72.8%. Internists were more likely to see patients
      for bacterial skin infections, herpes infection, exanthem, urticaria, and insect
      bites while dermatologists more commonly saw patients for actinic and seborrheic
      keratoses, warts, benign and malignant skin tumors, and psoriasis. CONCLUSIONS:
      The most common dermatologic diseases diagnosed by internists differ considerably
      from those diagnosed by dermatologists. Because dermatologists do much of the
      dermatology teaching of internal medicine residents, it is important to recognize
      these differences to place emphasis on the proper areas of study. Some common or
      serious skin conditions not often diagnosed by internists such as psoriasis and
      melanoma also deserve attention in internal medicine training programs.

PMID- 9554679
TI  - Trillion virion delay: time from testing positive for HIV to presentation for
      primary care.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals' initial
      presentation to medical care frequently occurs at a point of advanced
      immunosuppression. OBJECTIVES: To investigate the time between HIV testing and
      presentation to primary care. Also to examine factors associated with delayed
      presentation. METHODS: One hundred eighty-nine consecutive outpatients without
      prior primary care for HIV infection were assessed at 2 urban hospitals: Boston
      City Hospital, Boston, Mass, and Rhode Island Hospital, Providence.
      Sociodemographics, alcohol and drug use, social support, sexual beliefs and
      practices, and HIV testing issues were examined in bivariate and multivariate
      analyses for association with delay in presentation to primary care after
      positive test results for HIV. RESULTS: Of 189 patients, 74 (39%) delayed seeking
      primary care for more than 1 year, 61 (32%) delayed for more than 2 years, and 35
      (18%) for more than 5 years after an initial positive HIV serologic evaluation.
      The median CD4+ cell count of subjects was 0.28 x 10(9)/L (range, 0.001-1.71 x
      10(9)/L). In multiple linear regression analysis the following characteristics
      were found to be associated with delayed presentation to primary care after HIV
      testing: history of injection drug use (P<.001); not having a living mother
      (P=.01); not having a spouse or partner (P=.08); not being aware of HIV risk
      before testing (P<.001); and being notified of HIV status by mail or telephone
      (P=.002). An interaction effect between sex and screening for alcohol abuse was
      significant (P=.03) and suggested longer delays for men with positive screening
      test results (CAGE [an alcoholism screening questionnaire containing 4 structured
      questions], 2+) compared with men without positive screening test results or
      women. CONCLUSIONS: Patients with positive HIV test results often delay for more
      than a year before establishing primary medical care. Information readily
      available at the time of HIV testing concerning substance abuse, social support,
      and awareness of personal HIV risk status is useful in identifying patients who
      are at high risk of not linking with primary care. Patients who were notified of
      their HIV status by mail or telephone delayed considerably longer than those
      notified in person. Efforts to ensure primary care linkage at the time of
      notification of positive HIV serostatus are necessary to maximize benefits for
      both individual and public health and should be an explicit task of posttest
      counseling.

PMID- 9554680
TI  - Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on
      glucose, lipid, uric acid, and potassium levels in older men and women with
      isolated systolic hypertension: The Systolic Hypertension in the Elderly Program.
      SHEP Cooperative Research Group.
AB  - BACKGROUND: Previous studies often of short duration have raised concerns that
      antihypertensive therapy with diuretics and beta-blockers adversely alters levels
      of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension
      in the Elderly Program was a community-based, multicenter, randomized, double
      blind, placebo-controlled clinical trial of treatment of isolated systolic
      hypertension in men and women aged 60 years and older. This retrospective
      analysis evaluated development of diabetes mellitus in all 4736 participants in
      the Systolic Hypertension in the Elderly Program, including changes in serum
      chemistry test results in a subgroup for 3 years. Patients were randomized to
      receive placebo or treatment with active drugs, with the dose increased in
      stepwise fashion if blood pressure control goals were not attained: step 1, 12.5
      mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25
      mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS:
      After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in
      systolic and diastolic blood pressure than the placebo group (both groups,
      P<.001). New cases of diabetes were reported by 8.6% of the participants in the
      active treatment group and 7.5% of the participants in the placebo group (P=.25).
      Small effects of active treatment compared with placebo were observed with
      fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol
      (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02
      mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL];
      P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9
      mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and
      potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher
      risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive
      therapy with low-dose chlorthalidone (supplemented if necessary) for isolated
      systolic hypertension lowers blood pressure and its cardiovascular disease
      complications and has relatively mild effects on other cardiovascular disease
      risk factor levels.

PMID- 9554681
TI  - Tuberculosis among immigrants and refugees.
AB  - BACKGROUND: Overseas screening of immigrants and refugees applying for a visa to
      the United States identifies foreign-born individuals who are at high risk for
      tuberculosis (TB) or who have active TB. The system's effectiveness relies on
      further medical evaluation and follow-up of foreign-born individuals after their
      arrival in the United States. METHODS: Retrospective cohort study of 893
      immigrants and refugees who arrived in the United States from July 1, 1992,
      through December 31, 1993, with a destination of San Francisco, Calif, and a
      referral for further medical evaluation. MAIN OUTCOME MEASURES: Time to report to
      the local health department after arrival and the yield of active and preventable
      cases of TB from follow-up medical evaluations. RESULTS: Median time from arrival
      in the United States to seeking care in San Francisco was 9 days (range, 1-920
      days). Of 745 immigrants and refugees (83.4%) who sought further medical
      evaluation, 51 (6.9%) had active TB and 296 (39.7%) were candidates for
      preventive therapy. Being a refugee was an independent predictor of failure to
      seek further medical evaluation in the United States. Class B-1 disease status
      based on overseas TB screening (odds ratio, 3.5; 95% confidence interval, 2.0
      6.2) and being from mainland China (odds ratio, 4.4; 95% confidence interval, 1.9
      9.9) were independent predictors of TB diagnosed in San Francisco. CONCLUSIONS:
      Timely, adequate medical evaluation and follow-up care of immigrants and refugees
      has a relatively high yield and should be a high priority for TB prevention and
      control programs.

PMID- 9554682
TI  - Carotid and lower extremity arterial disease in patients with renal artery
      atherosclerosis.
AB  - BACKGROUND: Atherosclerotic lesions of the carotid and lower extremity arteries
      may be associated with renal artery stenosis and influence the management of
      patients with renal artery disease. OBJECTIVE: To document the prevalence and
      clinical features of carotid and lower extremity arterial disease in patients
      with renal artery atherosclerosis. METHODS: An analysis of baseline data on 149
      patients enrolled in a prospective natural history study of atherosclerotic renal
      artery stenosis. Patients with at least 1 abnormal renal artery by duplex
      scanning were eligible. Carotid artery disease was evaluated by duplex scanning,
      and ankle/brachial indices were used to assess the lower extremity arteries.
      Disease at each of the 3 arterial sites was classified as mild, moderate, or
      severe based on the extent of involvement on both sides. Serum urea nitrogen,
      creatinine, and lipid levels were also measured. RESULTS: Severe renal, carotid,
      or lower extremity arterial disease was present in 44%, 19%, and 21% of the
      patients, respectively. There was a trend for patients with increasing degrees of
      renal artery disease to have increasing degrees of carotid and lower extremity
      arterial disease. The prevalence of severe carotid artery disease increased from
      7% in the mild renal artery group to 28% in the severe renal artery group.
      Clinical factors that were most predictive of severe disease were elevated
      apolipoprotein B levels for the renal arteries, high serum urea nitrogen or
      creatinine levels for the carotid arteries, and smoking for the lower extremity
      arteries. CONCLUSIONS: There was a strong association between severe renal artery
      atherosclerosis and severe carotid artery disease. Patients with renal artery
      disease also had a high prevalence of lower extremity arterial disease. In this
      patient population, screening for lower extremity arterial disease can be
      reserved for those with signs or symptoms of peripheral ischemia. Noninvasive
      carotid screening is justified in patients with renal artery disease to detect
      asymptomatic lesions that require either immediate surgical treatment or serial
      follow-up for disease progression.

PMID- 9554683
TI  - Human granulocytic ehrlichiosis in New York.
AB  - BACKGROUND: Human granulocytic ehrlichiosis (HGE), a potentially fatal tick-borne
      disease, was first described in the upper Midwest in 1994. Following reports of
      suspected cases of ehrlichiosis from New York physicians, descriptive and case
      control studies were conducted to characterize the epidemiology and risk factors
      for HGE in New York residents. METHODS: Descriptive data were gathered from
      surveillance and laboratory reports and hospital records. A confirmed case was
      defined as either (1) a 4-fold change in total antibody titer to Ehrlichia equi
      by indirect immunofluorescence or (2) a polymerase chain reaction assay positive
      for Ehrlichia phagocytophila/E equi group DNA. A probable case was defined as an
      acute febrile illness and either (1) a single E equi titer greater than or equal
      to 80 or (2) morulae on a peripheral blood smear. The case-control study included
      patients with confirmed HGE 18 years of age or older with the onset of disease in
      1995 and 2 to 3 neighborhood-matched controls. RESULTS: During 1994 and 1995, the
      New York State Department of Health, Albany, received reports of 241 residents
      who were tested for HGE; 30 met the confirmed case definition and 34 met the
      probable case definition. The median age of patients was 46 years (age range, 9
      90 years), 35 (55%) were male, and 25 (45%) were hospitalized. Fever, headache,
      malaise, and myalgia were the most frequently reported symptoms. Fifty-six (88%)
      of the 64 patients resided in areas in which Lyme disease is hyperendemic. In the
      case-control analysis, cases were more likely than controls to have sustained a
      tick bite during 1995 (matched odds ratio, 5.0; 95% confidence interval, 0.9
      49.8). Cases and controls did not differ by occupational exposure to ticks,
      underlying chronic diseases, or measures taken to prevent tick bites.
      CONCLUSIONS: This study, which, to our knowledge, is the first population-based
      study of HGE, demonstrates the recent recognition of HGE in the state of New
      York. Control measures should be integrated with those for Lyme disease and
      should focus on minimizing contact with ticks and obtaining early treatment for
      infection.

PMID- 9554684
TI  - Carrier screening for cystic fibrosis, Gaucher disease, and Tay-Sachs disease in
      the Ashkenazi Jewish population: the first 1000 cases at New York University
      Medical Center, New York, NY.
AB  - BACKGROUND: By late 1993, the genes for cystic fibrosis and Gaucher disease and
      the mutations common among Ashkenazi Jews had been identified. In response to
      these advances, heterozygote screening for cystic fibrosis and Gaucher disease
      was added to the more than 20-year-old Tay-Sachs disease screening program at New
      York University Medical Center, New York, NY. OBJECTIVE: To review the outcomes
      from the first 1000 patients screened through this program. METHODS: Patients and
      their referring physicians were informed about the new carrier tests. At the time
      of screening, patients could choose their tests (hexosaminidase A by enzyme
      analysis for Tay-Sachs disease or mutation analysis for cystic fibrosis and
      Gaucher disease). All partners of Tay-Sachs and cystic fibrosis carriers were
      tested. Prenatal diagnosis was offered and performed for carrier couples or mixed
      marriage couples in whom the Ashkenazi Jewish partner was a carrier of Gaucher
      disease. Outcomes were measured by: (1) choice of tests, (2) decisions regarding
      prenatal diagnosis, and (3) phenotypes of children born to patients who underwent
      screening. RESULTS: The majority of Ashkenazi Jewish patients chose to have
      testing for all 3 diseases. If they previously underwent screening for Tay-Sachs
      disease, then they chose to undergo testing for cystic fibrosis and Gaucher
      disease. All carrier couples for each of these diseases went on to have prenatal
      testing. All mixed-marriage couples in whom the Jewish partner was found to be a
      carrier for Gaucher disease chose to have prenatal diagnosis. One fetus was
      identified as having cystic fibrosis. Since the program was initiated, no
      Ashkenazi Jewish baby has been born with any of these diseases at New York
      University Medical Center. CONCLUSIONS: New tests can be readily incorporated
      into established heterozygote screening programs. The Ashkenazi Jewish population
      described herein tends to choose testing for all conditions for which
      heterozygote screening is available.

PMID- 9554685
TI  - Member ratings of health care provided by 48 physician groups.
AB  - BACKGROUND: Satisfaction with health plan performance has been assessed
      frequently, but assessment of physician group performance is rare. OBJECTIVE: To
      present ratings of the care provided by physician groups to enrollees in a
      variety of capitated health maintenance organization plans. METHODS: A random
      sample was drawn of adult enrollees receiving managed health care from 48
      physician groups in a group practice association. Each individual in the sample
      was mailed a 12-page questionnaire and 7093 were returned (59% response rate).
      The mean age of those returning the questionnaire was 51 years; 65% were women.
      RESULTS: Reliability estimates for 6 multi-item satisfaction scales were
      excellent, and noteworthy differences in ratings among groups were observed. In
      particular, ratings of overall quality ranged from a low of 28 to a high of 68
      (mean, 50; SD, 10). Average scores for physician groups were strongly correlated
      across all scales, but no single group scored consistently highest or lowest on
      the different scales. Negative ratings of care were significantly related to the
      following: intention to switch to another physician group, difficulty in getting
      appointments, lengthy waiting periods in the reception area and examination room,
      the inability to get consistent care from one physician for routine visits, and
      not being informed by the office staff when there was a delay in seeing the
      primary care provider. CONCLUSIONS: Monitoring of health care quality at the
      physician group level is possible, and could be used for benchmarking, internal
      quality improvement, and for providing information to the public about how these
      physician groups will meet its needs.

PMID- 9554686
TI  - End-stage renal disease in specific ethnic and racial groups: risk factors and
      benefits of antihypertensive therapy.
AB  - During the past few years, it has become apparent that there are factors that
      place a person at greater risk for the development and progression of renal
      failure. This has been documented since the early 1980s by the United States
      Renal Data System that has collected data confirming that end-stage renal disease
      occurs at a greater rate in certain subpopulations of Americans. It is evident
      from an examination of the data that African Americans and American Indians have
      an incidence of end-stage renal disease that is not proportional to their
      percentage of the total population. In fact, African Americans and American
      Indians are reported to have at least a 4-fold greater incidence of end-stage
      renal disease than white Americans. There have been 5 factors identified:
      hypertension, glucose intolerance, insulin resistance, salt sensitivity, and
      hyperlipidemia, which may play a greater role in these subpopulations. In
      addition, as with other populations, lifestyle issues may serve to alter these
      primary risk factors or may act as direct modulators of renal disease
      progression. There is also a possibility that interactions between risk factors
      frequently occur that may modify the development or progression of the disease.
      This article reviews these risk factors and emphasizes the interaction between
      hypertension and the other factors. In addition, the effects of antihypertensive
      agents on risk factors and on renal outcome are emphasized. Where possible,
      issues specific to African Americans and American Indians are underscored;
      however, one must accept that the database on these populations is only now
      developing. This review should help the clinician make appropriate choices when
      prescribing antihypertensive therapy for patients who may be at risk of
      developing progressive renal failure.

PMID- 9554687
TI  - Diagnostic utility of the polymerase chain reaction in 2 cases of suspected
      Whipple disease.
AB  - We describe 2 patients with a diagnosis of Whipple disease in whom the usual
      antibiotic therapy failed. A polymerase chain reaction-based test was used to
      identify the recently described Whipple bacillus, Tropheryma whippelii. In one
      case, the diagnosis was confirmed, whereas in the second case, which had been
      histologically diagnosed as Whipple disease of the brain, the process was
      identified as a monocyte-derived histiocytosis. In conclusion, Whipple disease
      can be distinguished from other diseases with similar histological features with
      the use of a polymerase chain reaction-based test.

PMID- 9554689
TI  - Depression, adherence behavior, and coronary disease outcomes.

PMID- 9554688
TI  - More evidence on safety of intramuscular immune serum globulin produced from
      plasma unscreened for anti-hepatitis C virus antibodies.

PMID- 9554690
TI  - Intractable hiccups induced by the use of megestrol acetate.

PMID- 9554691
TI  - Group A streptococcal meningitis.

PMID- 9554693
TI  - Influence of extremely low frequency magnetic fields on chromosomes and the
      mitotic cycle in Vicia faba L., the broad bean.
AB  - Vicia faba seedlings were subjected to one of the following magnetic fields
      continuously for 3 days: 0 Hz (DC) at 5 mT, 50 Hz at 1.5 mT, 60 Hz at 1.5 mT, and
      75 Hz at 1.5 mT. The lengths of all the phases of mitosis differed from the
      controls in all treatments using alternating magnetic fields and for prophase and
      metaphase in the DC condition. In particular, all treatments increased the length
      of prophase significantly in meristematic root-tip cells compared with the
      controls. The implications of these results for chromosome coiling are discussed.
      The length of prophase, however, did not vary significantly between any of the
      treatments. Furthermore, none of the exposed seedlings had a greater frequency of
      chromosome breakages above that of the control plants.

PMID- 9554692
TI  - Alternate indices of electric and magnetic field exposures among Ontario
      electrical utility workers.
AB  - Epidemiologic studies examining the risk of cancer among occupational groups
      exposed to electric fields (EF) and or magnetic fields (MF) have relied on
      traditional summaries of exposure such as the time weighted arithmetic or
      geometric mean exposure. Findings from animal and cellular studies support the
      consideration of alternative measures of exposure capable of capturing threshold
      and intermittent measures of field strength. The main objective of this study was
      to identify a series of suitable exposure metrics for an ongoing cancer incidence
      study in a cohort of Ontario electric utility workers. Principal components
      analysis (PCA) and correlational analysis were used to explore the relationships
      within and between series of EF and MF exposure indices. Exposure data were
      collected using personal monitors worn by a sample of 820 workers which yielded
      4247 worker days of measurement data. For both EF and MF, the first axis of the
      PCA identified a series of intercorrelated indices that included the geometric
      mean, median and arithmetic mean. A considerable portion of the variability in EF
      and MF exposures were accounted for by two other principal component axes. The
      second axes for EF and MF exposures were representative of the standard deviation
      (standard deviation) and thresholds of field measures. To a lesser extent, the
      variability in the exposure variable was explained by time dependent indices
      which consisted of autocorrelations at 5 min lags and average transitions in
      field strength. Our results suggest that the variability in exposure data can
      only be accounted for by using several exposure indices, and consequently, a
      series of metrics should be used when exploring the risk of cancer owing to MF
      and EF exposure in this cohort. Furthermore, the poor correlations observed
      between indices of MF and EF reinforce the need to be take both fields into
      account when assessing the risk of cancer in this occupational group.

PMID- 9554694
TI  - Evaluation of potential health effects of 10 kHz magnetic fields: a rodent
      reproductive study.
AB  - New technology involving the use of high-frequency inductive power distribution
      (HID) has recently been developed for use in materials handling and personnel
      transfer. Sinusoidal magnetic fields at a frequency of 10 kHz with field
      intensities of approximately 0.2 mT are generated directly between the current
      carrying coils of this equipment. Effects of 10 kHz magnetic fields on cell
      division, migration, and differentiation have never been previously investigated.
      To evaluate potential effects on these parameters, a rodent reproductive study
      was undertaken using Wistar rats. Exposures were at 0.095, 0.24, and 0.95 mT with
      a background exposure of 5-10 microT. Three sets of parental rats were exposed
      continuously for 20-23.5 h/day to the fields: maternal rats during gestation,
      paternal rats for at least 45 days prior to mating and maternal rats 1 month
      prior to mating. Exposure phases thus covered spermatogenesis, maturation of the
      ovum and ovulation, fertilization, implantation, embryogenesis, organogenesis,
      and maturation of the fetus immediately prior to parturition. In all experiments
      pregnancy outcome was assessed. These studies failed to demonstrate any
      reproductive toxicity resulting from maternal or fetal exposure during gestation
      or following paternal or maternal exposure for several weeks prior to mating. No
      quantitative or qualitative effects on spermatogenesis occurred after exposure,
      and no effects on the estrous cycle or ovulation could be demonstrably linked to
      the 10 kHz magnetic field exposure at 0.095, 0.25, or 0.95 mT. Where possible,
      parental clinical chemistry and hematology were also examined. As in mouse
      toxicology studies previously reported, minor differences were observed between
      control and treated groups. These were regarded as statistically, but not
      biologically, significant and could not categorically be attributed to magnetic
      field exposure.

PMID- 9554695
TI  - 60 Hz magnetic field exposure and urinary 6-sulphatoxymelatonin levels in the
      rat.
AB  - Four separate experiments were carried out to investigate the effect of extremely
      low frequency magnetic field (MF) exposure (60 Hz, 1 mT rms) on urinary 6
      sulphatoxymelatonin (aMT6s) levels in Sprague-Dawley rats. In the first
      experiment, immature male rats maintained under a regular 12 h daily photoperiod
      (white fluorescent light) were exposed to a 20 h daily MF exposure for 6 weeks.
      The second experiment was similar to the first, except that the MF exposure was
      limited to 10 days. In the third experiment, adult male rats acclimated to a
      combination of continuous dim red light and regular 12 h daily photoperiod (white
      fluorescent) were subjected to a single 1 h exposure to intermittent MF (1 min on
      and 1 min off cycles), 2 h before fluorescent lights went off. The fourth
      experiment was similar to the third, except that the animals received 2
      consecutive days of 20 h daily exposure to intermittent MF, beginning 1 h before
      the fluorescent lights went off each day. In all four experiments, the circadian
      profile of urinary aMT6s was examined before, during, and after the MF exposure.
      No significant effect of 1 mT MF on indoleamine metabolism was observed in any of
      the above experiments. However, in one of the experiments (no. 4), both the
      control and the MF groups showed a lower aMT6s level during the exposure days,
      when compared with that of pre- and post-exposure days, suggesting that the
      existence of possible effects with lower field strengths at the range of stray
      field cannot be ruled out.

PMID- 9554696
TI  - A physical analysis of the ion parametric resonance model.
AB  - We show, in elementary terms, using for the most part only elementary
      mathematics, the physical bases for the ion parametric resonance model so as to
      clarify the assumptions and consequences of the model. The analysis shows why,
      contrary to earlier conclusions, no combination of weak DC and AC magnetic fields
      can modify the transition rate to the ground state of excited ions. Although
      reinterpretations of the biological consequences of the motion of the excited
      ions circumvent that particular objection to the model, those changes introduce
      other difficulties. Also, other objections to the mechanism still stand; hence
      the model cannot account for any purported biological effects of weak extremely
      low frequency magnetic fields.

PMID- 9554697
TI  - Analysis of the effect of a 60 Hz AC field on histamine release by rat peritoneal
      mast cells.
AB  - Reports have indicated effects of electromagnetic fields on inflammatory
      processes in vivo. To begin a systematic approach toward separating and examining
      the many components of such responses, we created and tested a temperature
      controlled device to develop 5 mT 60 Hz magnetic fields for studies of the
      effects of fields on mast cells, a key component in acute inflammatory responses.
      Such fields have been reported to modulate cell activity, including changes in
      membrane function, in various systems. The magnetic field was generated using a
      solenoid and calibrated with an induction probe. Tests of mast cell function were
      determined by histamine release response to stimulation by compound 48/80, using
      both an "expose then test" and a "test during exposure" protocol. Aliquots not
      treated with 48/80 were used to evaluate field treatment effects on spontaneous
      histamine release. Freshly harvested rat peritoneal mast cells were exposed to
      the magnetic field for periods of 30 min to 2 h at 37 degrees C. They showed no
      significant degranulation during treatment, nor did they show reduced sensitivity
      to the degranulating agent 48/80. These observations are consistent with a model
      in which such processes are exclusively reflexive by the cells using field
      independent membrane systems. This observation is very useful and was needed
      before examining longer term exposures in which gene expression in the cells
      might be influenced; this is the first such report of in vitro exposure of
      purified mast cells under these conditions and will further the study of the
      effects of electromagnetic fields on cell types active in acute inflammation.

PMID- 9554698
TI  - Human sleep under the influence of pulsed radiofrequency electromagnetic fields:
      a polysomnographic study using standardized conditions.
AB  - To investigate the influence of radiofrequency electromagnetic fields (EMFs) of
      cellular phone GSM signals on human sleep electroencephalographic (EEG) pattern,
      all-night polysomnographies of 24 healthy male subjects were recorded, both with
      and without exposure to a circular polarized EMF (900 MHz, pulsed with a
      frequency of 217 Hz, pulse width 577 micros, power flux density 0.2 W/m2.
      Suppression of rapid eye movement (REM) sleep as well as a sleep-inducing effect
      under field exposure did not reach statistical significance, so that previous
      results indicating alterations of these sleep parameters could not be replicated.
      Spectral power analysis also did not reveal any alterations of the EEG rhythms
      during EMF exposure. The failure to confirm our previous results might be due to
      dose-dependent effects of the EMF on the human sleep profile.

PMID- 9554699
TI  - Acetylcholine release and the cholinergic genomic locus.
AB  - Choline acetyltransferase and vesicular acetylcholine-transporter genes are
      adjacent and coregulated. They define a cholinergic locus that can be turned on
      under the control of several factors, including the neurotrophins and the
      cytokines. Hirschprung's disease, or congenital megacolon, is characterized by
      agenesis of intramural cholinergic ganglia in the colorectal region. It results
      from mutations of the RET (GDNF-activated) and the endothelin-receptor genes,
      causing a disregulation in the cholinergic locus. Using cultured cells, it was
      shown that the cholinergic locus and the proteins involved in acetylcholine (ACh)
      release can be expressed separately ACh release could be demonstrated by means of
      biochemical and electrophysiological assays even in noncholinergic cells
      following preloading with the transmitter. Some noncholinergic or even
      nonneuronal cell types were found to be capable of releasing ACh quanta. In
      contrast, other cells were incompetent for ACh release. Among them, neuroblastoma
      N18TG-2 cells were rendered release-competent by transfection with the
      mediatophore gene. Mediatophore is an ACh-translocating protein that has been
      purified from plasma membranes of Torpedo nerve terminal; it confers a
      specificity for ACh to the release process. The mediatophores are activated by
      Ca2+; but with a slower time course, they can be desensitized by Ca2+. A strictly
      regulated calcium microdomain controls the synchronized release of ACh quanta at
      the active zone. In addition to ACh and ATP, synaptic vesicles have an ATP
      dependent Ca2+ uptake system; they transiently accumulate Ca2+ after a brief
      period of stimulation. Those vesicles that are docked close to Ca2+ channels are
      therefore in the best position to control the profile and dynamics of the Ca2+
      microdomains. Thus, vesicles and their whole set of associated proteins (SNAREs
      and others) are essential for the regulation of the release mechanism in which
      the mediatophore seems to play a key role.

PMID- 9554700
TI  - Extracellular nucleotide signaling in the inner ear.
AB  - Extracellular nucleotides, particularly adenosine 5'-triphosphate (ATP), act as
      signaling molecules in the inner ear. Roles as neurotransmitters,
      neuromodulators, and as autocrine or paracrine humoral factors are evident. The
      diversity of the signaling pathways for nucleotides, which include a variety of
      ATP-gated ion channels (assembled from different subtypes of P2X-receptor
      subunit) and also different subtypes of G protein-coupled nucleotide receptors
      (P2Y receptors) supports a major physiological role for ATP in the regulation of
      hearing and balance. Almost invariably both P2X and P2Y receptor expression is
      apparent in the complex tissue structures associated with the inner-ear
      labyrinth. However P2X-receptor expression, commonly associated with fast
      neurotransmission, is apparent not only with the cochlear and vestibular primary
      afferent neurons, but also appears to mediate humoral signaling via ATP-gated ion
      channel localization to the endolymphatic surface of the cochlear sensory
      epithelium (organ of Corti). This is the site of the sound-transduction process
      and recent data, including both electrophysiological, imaging, and
      immunocytochemistry, has shown that the ATP-gated ion channels are colocalized
      here with the mechano-electrical transduction channels of the cochlear hair
      cells. In contrast to this direct action of extracellular ATP on the sound
      transduction process, an indirect effect is apparent via P2Y-receptor expression,
      prevalent on the marginal cells of the stria vascularis, a tissue that generates
      the standing ionic and electrical gradients across the cochlear partition. The
      site of generation of these gradients, including the dark-cell epithelium of the
      vestibular labyrinth, may be under autocrine or paracrine regulation mediated by
      P2Y receptors sensitive to both purines (ATP) and pyrimidines such as UTP. There
      is also emerging evidence that the nucleoside adenosine, formed as a breakdown
      product of ATP by the action of ectonucleotidases and acting via P1 receptors, is
      also physiologically significant in the inner ear. P1-receptor expression
      (including A1, A2, and A3 subtypes) appear to have roles associated with stress,
      acting alongside P2Y receptors to enhance cochlear blood flow and to protect
      against the action of free radicals and to modulate the activity of membrane
      conductances. Given the positioning of a diverse range of purinergic-signaling
      pathways within the inner ear, elevations of nucleotides and nucleosides are
      clearly positioned to affect hearing and balance. Recent data clearly supports
      endogenous ATP- and adenosine-mediated changes in sensory transduction via a
      regulation of the electrochemical gradients in the cochlea, alterations in the
      active and passive mechanical properties of the cells of the sensory epithelium,
      effects on primary afferent neurons, and control of the blood supply. The field
      now awaits conclusive evidence linking a physiologically-induced modulation of
      extracellular nucleotide and nucleoside levels to altered inner ear function.

PMID- 9554701
TI  - Age-related alteration of PKC, a key enzyme in memory processes: physiological
      and pathological examples.
AB  - Brain aging is characterized by a progressive decline of the cognitive and memory
      functions. It is becoming increasingly clear that protein phosphorylation and, in
      particular, the activity of the calcium-phospholipid-dependent protein kinase C
      (PKC) may be one of the fundamental cellular changes associated with memory
      function. PKC is a multigene family of enzymes highly expressed in brain tissues.
      The activation of kinase C is coupled with its translocation from the cytosol to
      different intracellular sites and recent studies have demonstrated the key role
      played by several anchoring proteins in this mechanism. PKC-phosphorylating
      activity appears to be impaired during senescence at brain level in a strain
      dependent fashion in rodents. Whereas the levels of the various isoforms do not
      show age-related alterations, the enzyme translocation upon phorbol-ester
      treatment is deficitary among all strains investigated. Anchoring proteins may
      contribute to this activation deficit. We discuss also modifications of the PKC
      system in Alzheimer's disease that may be related to pathological alterations in
      neurotransmission. A better insight of the different factors controlling brain
      PKC activation may be important not only for elucidating the molecular basis of
      neuronal transmission, but also for identifying new approaches for correcting or
      even preventing age-dependent changes in brain function.

PMID- 9554702
TI  - Gender specificity in the neural regulation of the response to stress: new leads
      from classical paradigms.
AB  - Pronounced gender-related differences are observable in the regulation of the
      limbic-hypothalamic-pituitary-adrenal (LHPA) activity under basal and stress
      related conditions, and by circulating glucocorticoid levels. This article
      reviews recent studies that have unequivocally demonstrated that these
      differences emerge from the organizational effects of gonadal steroids during
      early brain development. Although largely masked by the dominating role of
      glucocorticoids in maintaining feedback thresholds, gonadal steroids continue to
      exert gender-specific activational effects on the LHPA axis through adulthood.
      The importance of these modulatory effects of gonadal steroids may be reflected
      in gender differences in the incidence of psychopathologies that are accompanied
      by symptoms of LHPA dysregulation. One goal of this review is to highlight the
      need for further investigations into the (still elusive) cellular and molecular
      mechanisms underlying the activational effects of sex steroids, which may provide
      leads for neuroprotective hormone replacement strategies.

PMID- 9554705
TI  - Disabled doctors: the insurance industry seeks a second opinion.
AB  - This article focuses on disability in the professional work force, especially
      among physicians, and includes a background on private disability insurance in
      the United States, a discussion of problems experienced by the insurance industry
      over the past few years, a review of relevant case law on private disability, and
      legal and clinical issues involved in performing independent medical evaluations.

PMID- 9554703
TI  - Role of MAP kinase in neurons.
AB  - Extracellular stimuli such as neurotransmitters, neurotrophins, and growth
      factors in the brain regulate critical cellular events, including synaptic
      transmission, neuronal plasticity, morphological differentiation and survival.
      Although many such stimuli trigger Ser/Thr-kinase and tyrosine-kinase cascades,
      the extracellular signal-regulated kinases, ERK1 and ERK2, prototypic members of
      the mitogen-activated protein (MAP) kinase family, are most attractive candidates
      among protein kinases that mediate morphological differentiation and promote
      survival in neurons. ERK1 and ERK2 are abundant in the central nervous system
      (CNS) and are activated during various physiological and pathological events such
      as brain ischemia and epilepsy. In cultured hippocampal neurons, simulation of
      glutamate receptors can activate ERK signaling, for which elevation of
      intracellular Ca2+ is required. In addition, brain-derived neurotrophic factor
      and growth factors also induce the ERK signaling and here, receptor-coupled
      tyrosine kinase activation has an association. We describe herein intracellular
      cascades of ERK signaling through neurotransmitters and neurotrophic factors.
      Putative functional implications of ERK and other MAP-kinase family members in
      the central nervous system are give attention.

PMID- 9554706
TI  - Expert witness travel dilemmas: a pilot study of billing practices.
AB  - A pilot study was performed, by questionnaire, on the strategies that expert
      witnesses use in calculating billing for travel on forensic cases. The authors
      tentatively conclude that as the complexity of the travel situation increases, a
      tendency toward redundant billing emerges. The results--the first of their kind-
      are presented with their implications for this and future studies.

PMID- 9554704
TI  - Measuring human brain GABA in vivo: effects of GABA-transaminase inhibition with
      vigabatrin.
AB  - Gamma-aminobutyric acid (GABA) plays a pivotal role in suppressing the origin and
      spread of seizure activity. Low occipital lobe GABA was associated with poor
      seizure control in patients with complex partial seizures. Vigabatrin
      irreversibly inhibits GABA-transaminase, raising brain and cerebrospinal fluid
      (CSF) GABA concentrations. The effect of vigabatrin on occipital lobe GABA
      concentrations was measured by in vivo nuclear magnetic-resonance spectroscopy.
      Using a single oral dose of vigabatrin, the rate of GABA synthesis in human brain
      was estimated at 17% of the Krebs cycle rate. As the daily dose of vigabatrin was
      increased to up to 3 g, the fractional elevation of brain GABA was similar to CSF
      increase. Doubling the daily dose from 3 to 6 g failed to increase brain GABA
      further. Increased GABA concentrations appear to reduce GABA synthesis in humans
      as it does in animals. With traditional antiepileptic drugs, remission of the
      seizure disorder was associated with normal GABA levels. With vigabatrin,
      elevated CSF and brain GABA was associated with improved seizure control.
      Vigabatrin enhances the vesicular and nonvesicular release of GABA. The release
      of GABA during seizures may be mediated in part by transporter reversal that may
      serve as an important protective mechanism. During a seizure, this mechanism may
      be critical in stopping the seizure or preventing its spread.

PMID- 9554707
TI  - "Courtroom whores"?--or why do attorneys call us?: findings from a survey on
      attorneys' use of mental health experts.
AB  - Mental health professionals who serve as expert witnesses are repeatedly
      characterized as (in the words of one recent author) "Whores of the Court."
      However, scholars have published little systematically gathered data about why
      attorneys seek mental health opinions and the criteria they use for selecting
      experts. We investigated these issues using a mailed survey of attorneys and
      judges. A slight majority of attorney respondents had requested mental health
      professionals' opinion in the previous year. The most important factors in
      selecting experts were their knowledge, ability to communicate, and local
      reputation; national reputation and scholarly writings were least important.
      Forty-nine percent of the responding attorneys said that receiving a favorable
      opinion was a "very important" or "essential" consideration, although this did
      not necessarily mean they wanted a dishonest opinion. Our findings suggest that
      most forensic work is performed by mental health professionals who are chosen
      because of their knowledge, communication skills, and local reputations.

PMID- 9554708
TI  - Prototypes of intrafamily homicide and serious assault among insanity acquittees.
AB  - Public concern with societal violence is intensified when persons who have been
      found not guilty by reason of insanity (NGRI) of having committed a homicide or
      serious assault are returned to the community. Successful management of such
      acquittees in the community requires a sophisticated understanding of the person
      and the illness within the larger context of the violent incident, the family,
      the community, and the culture. In this article, we present an analysis of
      psychotic violence within a family context. A qualitative study of 64 subjects
      who were found NGRI of killing or seriously injuring a family member resulted in
      four prototypes of intrafamilial homicide/assault: Till Death Us Do Part;
      Overwhelming Burden, Elimination of the Limit Setter; and Family-Focused
      Delusional Killing. The prototypes are presented as a model for developing
      management strategies both for future risk assessment and for successful
      transition of the insanity acquittee into the community.

PMID- 9554709
TI  - Relating competency status to functional status at discharge in patients with
      chronic mental illness.
AB  - This study assessed performance on a screening test of competency to consent to
      treatment, the Hopkins Competency Assessment Test (HCAT), in a population
      diagnosed with chronic mental illness, and examined the relationship between HCAT
      performance and functional status at discharge. We hypothesized that patients
      with chronic mental illness who failed the HCAT would also have problems in
      performing activities of daily living at the time of discharge. Forty-three
      patients on a short-stay psychiatric service were administered the following
      screening tests: (1) Mini-Mental State Exam (MMSE), on admission; (2) the HCAT,
      approximately four to five days after admission; (3) At discharge, the Milwaukee
      Evaluation of Daily Living Skills (MEDLS), and the Occupational Therapy Task
      Observation Scale (OTTOS). Analyses included correlation between the competency
      measure HCAT and the functional measures; sensitivity, specificity, and positive
      and negative predictive values of the HCAT score; and odds ratio and chi-square
      analysis. The HCAT was highly correlated with the MEDLS and OTTOS. The HCAT was
      not sensitive in identifying impairment on either functional measure, but when
      patients failed the HCAT, they were likely to be functionally impaired at
      discharge. The negative predictive value of the HCAT was greater than the
      positive predictive value. Patients who failed HCAT were significantly more
      likely to have an MMSE score lower than 27 and less than 12 years of school.
      Seven of forty-three (16.3%) patients failed a screening measure of competency,
      indicating that there is a subgroup of chronically mentally ill patients who may
      not understand issues of informed consent. Patients who failed the HCAT were more
      likely to be functionally impaired at discharge. Cognitive impairment and low
      education are important factors in failure to pass competency screening.
      Competency screening along with screening for cognitive impairment can be useful
      in identifying patients at risk for poor functional status at discharge.

PMID- 9554710
TI  - Corruption in law enforcement: a paradigm of occupational stress and deviancy.
AB  - In the closed society of a law enforcement agency, factors such as the conspiracy
      of silence, authoritarian supervision, and police discretion contribute to
      corruption. This article describes various types of corrupt behavior by police
      officers, reports the incidence of corruption in law enforcement agencies,
      discusses psychiatric conditions that may arise from corruption and also
      contribute to further corruption, and reviews proposed remedies for corruption.
      It also suggests that an understanding of corruption in law enforcement might be
      helpful in understanding, correcting, and preventing corruption in other
      professions, including medicine.

PMID- 9554711
TI  - A comparison of youthful inmates who have committed violent versus nonviolent
      crimes.
AB  - The incidence of violent crimes committed by youthful offenders in the United
      States is increasing. In this report, 150 inmates in a prison for youths (ages 14
      to 24 years) who were treated by a psychiatrist were compared with 150 control
      subjects on several parameters including those who had committed violent crimes
      (V) versus those who had committed nonviolent crimes (NV). There were more
      similarities than differences between those who had committed V versus NV crimes.
      There was no statistically significant difference between the V and NV groups in
      most diagnostic categories, the Beck Hopelessness Scale, the IQ scale, the MMPI
      scores, job stability, and whether they were treated by a psychiatrist or not.
      There were, however, some significant differences. The V group was younger than
      the NV group; those with a diagnosis of paranoid schizophrenia disorder had
      committed V crimes, while those with a diagnosis of dysthymic disorder had
      committed NV crimes.

PMID- 9554713
TI  - Competency to stand trial in preadjudicatory juveniles and adults.
AB  - This study compared the competency to stand trial (CST) of 108 juveniles (ages 7
      to 16 years) and 145 adults (17 years or older) undergoing pretrial, court
      ordered forensic psychiatric evaluations. Adults were superior on both global and
      specific competency abilities (p < .001). Clustered by age (<13, 13 and 14, 15
      and 16 years old), preteens accused of crimes failed to meet a Dusky v. United
      States standard, while 13- and 14-year-olds displayed an equal mix of abilities
      and deficits. Mid-adolescents (ages 15 and 16) were equivalent to adults in CST
      abilities except in their knowledge about plea bargaining elements. The
      ramifications of CST in felony juvenile transfer to adult court as well as the
      needs for ecologically valid, empirically based CST research on adolescents is
      discussed.

PMID- 9554712
TI  - Extended civil commitment for dangerous psychiatric patients.
AB  - Mental health clinicians are increasingly held civilly liable for the dangerous
      acts of their psychiatric patients. One area of liability is the negligent
      release of involuntarily committed patients who engage in dangerous acts after
      their hospital discharge. All states have provisions for extended involuntary
      commitment for mentally ill dangerous patients. We examined extended civil
      commitment petitions in Los Angeles County, California, and found that the great
      majority were rejected. While the standard for extended civil commitment in
      California includes verbal threats of substantial physical harm, deputy district
      attorneys tended to reject petitions initiated by clinicians when verbal threats
      were the sole criterion of dangerousness. This tendency by deputy district
      attorneys can be quite confusing for clinicians. Mental health professionals'
      liability has sensitized them to the legal implications of patients' verbal
      threats of harm; attorneys do not incur the same legal liability and are not so
      sensitized.

PMID- 9554714
TI  - Stone walls do not a prison psychiatrist make.

PMID- 9554715
TI  - An introduction to correctional psychiatry: Part III.
AB  - This article, which is the last of three parts, provides an overview of relevant
      national guidelines/standards for providing mental health services within a
      correctional setting and describes essential characteristics of mental health
      systems designed to meet constitutional standards. Part III addresses issues
      pertinent to treatment programs for inmates with serious mental illnesses;
      confidentiality; involuntary treatment; quality assurance; management information
      systems; and research.

PMID- 9554716
TI  - Disability discrimination and Parker v. Metropolitan Life: separate, but equal?
AB  - In August 1997, the Sixth Circuit U.S. Court of Appeals ruled that disability
      insurance obtained as an employment benefit is not a "physical place" protected
      by Title III of the Americans With Disabilities Act (ADA). The majority held that
      because benefits were obtained from an employer instead of from an insurance
      office, the insurance plan's disparity between mental health benefits and
      benefits for physical disabilities did not constitute "discrimination" as defined
      by Title I of the ADA. Other circuit courts have held that illness-specific
      discrimination in disability insurance coverage is indeed prohibited under Title
      III. The conflict between the circuit courts may ultimately work its way to the
      U.S. Supreme Court.

PMID- 9554717
TI  - Privatized managed care and forensic mental health services.
AB  - Managed care for mental health services, which began in the private, commercial
      sector, has spread over the past few years to the public mental health sector as
      well. Recently, states have begun considering whether to include the forensic
      population within their privatized managed care systems. This article explores
      some of the complexities and special challenges unique to forensic services and
      notes some of the problems that might be incurred if the forensic population were
      included in a managed care system.

PMID- 9554718
TI  - A theory of ethics for forensic psychiatry.

PMID- 9554719
TI  - How are neurons specified: master or positional control?

PMID- 9554720
TI  - Getting the most out of noise in the central nervous system.
AB  - Rather than merely a nuisance, noise in biological systems is a useful property.
      Before patch-clamp methods were invented, analysis of membrane current noise
      provided the first solid, if indirect, evidence for the existence of ion
      conducting pores with discrete conductance levels. Although supplanted by single
      channel recording techniques for most tasks, analysis of current membrane noise
      remains useful for certain problems, such as determining the properties of
      channels with rapid kinetics that open with a high probability and desensitize,
      channels localized at synapses, channels with an unusually low unitary
      conductance and open-channel noise. In addition, the role of noise in information
      processing in the CNS is increasingly being recognized. In this article, we
      summarize the analysis of current membrane noise with an emphasis on what the
      technique is still useful for, and discuss the role for noise in information
      processing.

PMID- 9554721
TI  - Schizophrenia as failure of hemispheric dominance for language.

PMID- 9554722
TI  - Schizophrenia as failure of hemispheric dominance for language.

PMID- 9554723
TI  - Schizophrenia as failure of hemispheric dominance for language.

PMID- 9554724
TI  - Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel
      function.
AB  - Voltage-dependent Ca2+ channels are heteromeric complexes found in the plasma
      membrane of virtually all cell types and show a high level of
      electrophysiological and pharmacological diversity. Associated with the pore
      forming alpha 1 subunit are the membrane anchored, largely extracellular alpha2
      delta, the cytoplasmic beta and sometimes a transmembrane gamma subunit; these
      subunits dramatically influence the properties and surface expression of these
      channels. Effects vary depending on subunit isoforms, suggesting that functional
      diversity of native channels reflects heterogeneity of combinations. Interaction
      sites between subunits have been identified and advances have been made in our
      understanding of the molecular basis of functional effects of the auxiliary
      subunits, their capacity to be regulated by G proteins, and their interaction
      with related cellular systems.

PMID- 9554725
TI  - Do chemokines mediate leukocyte recruitment in post-traumatic CNS inflammation?
AB  - Hematogenous leukocytes infiltrate the CNS after inflammatory stimuli, including
      infection, mechanical trauma and excitotoxic neuronal necrosis. However,the role
      of leukocytic inflammation in promoting or hindering tissue repair is poorly
      understood. Identification of signals that lead to leukocyte recruitment and
      activation is essential for the designing of interventions that modulate
      inflammation, thus improving neurological outcome. Chemokines are small
      pleiotropic chemoattractant cytokines whose target specificity suggests an
      important role in determining the cellular composition of inflammatory
      infiltrates. Chemokine expression profiles in the CNS during autoimmune and post
      traumatic inflammation correlate well with the composition of leukocyte
      infiltrates, and expression studies in systems such as transgenic mice, suggest
      that chemokines have potent functional attributes in CNS physiology. We propose
      that selective chemokine expression by CNS cells is crucial for post-traumatic
      leukocyte accumulation.

PMID- 9554726
TI  - How well do we understand the cochlea?
AB  - As sensory cells, hair cells within the mammalian inner ear convert sounds into
      receptor potentials when their projecting stereocilia are deflected. The organ of
      Corti of the cochlea contains two types of hair cell, inner and outer hair cells,
      which differ in function. It has been appreciated for over two decades that
      although inner hair cells act as the primary receptor cell for the auditory
      system, the outer hair cells can also act as motor cells. Outer hair cells
      respond to variation in potential, and change length at rates unequalled by other
      motile cells. The forces generated by outer hair cells are capable of altering
      the delicate mechanics of the cochlear partition, increasing hearing sensitivity
      and frequency selectivity. The discovery of such hair-cell motility has modified
      the view of the cochlea as a simple frequency analyser into one where it is an
      active non-linear filter that allows only the prominent features of acoustic
      signals to be transmitted to the acoustic nerve by the inner hair cells. In this
      view, such frequency selectivity arises through the suppression of adjacent
      frequencies, a mechanical effect equivalent to lateral inhibition in neural
      structures. These processes are explained by the interplay between the
      hydrodynamic interactions among different parts of the cochlear partition and the
      effective non-linear behaviour of the cell motor.

PMID- 9554727
TI  - Pro-epileptic changes in synaptic function can be accompanied by pro-epileptic
      changes in neuronal excitability.
AB  - Repetitive sensory input, stroboscopic lights or repeated sounds can induce
      epileptic seizures in susceptible individuals. In order to understand the process
      we have to consider multiple factors. The output of a set of neurones is
      determined by the amount of excitatory synaptic input, the degree of positive
      feedback and their inherent electrical excitability, which can be modified by
      synaptic inhibition. Recent research has shown that it is possible to separate
      these phenomena, and that they do not always behave in unison.

PMID- 9554728
TI  - Temporal stability of defibrillation thresholds with an active pectoral lead
      system.
AB  - INTRODUCTION: Monophasic defibrillation thresholds rise over time with a variety
      of lead systems. These chronic changes are attenuated or eliminated by biphasic
      waveforms, although the effect appears dependent upon the lead system. With the
      downsizing of pulse generator size to allow for routine pectoral implantation,
      active can lead systems have now become standard. However, the temporal stability
      of such lead systems has not been evaluated previously. METHODS AND RESULTS: This
      study was a prospective assessment of the changes of active pectoral
      defibrillation thresholds over time. Thresholds were measured at implant,
      predischarge, and at a mean follow-up of 50 days in 46 patients with a uniform
      testing protocol and shock polarity. The lead system was a dual-coil Endotak DSP
      lead with an active pectoral pulse generator. Defibrillation thresholds were
      9.9+/-5.5 J at implantation, 8.5+/-6.0 J predischarge, and 7.6+/-5.5 J at follow
      up (ANOVA, P = 0.007). Moreover, only two patients developed an increased
      threshold > 5 J, and no patient had an inadequate safety margin at follow-up.
      CONCLUSION: These results indicate that active pectoral defibrillation thresholds
      are stable over the first 2 months postimplantation and question the need for
      routine serial defibrillation threshold testing.

PMID- 9554729
TI  - Intracardiac stimulation of human parasympathetic nerve fibers induces negative
      dromotropic effects: implication with the lesions of radiofrequency catheter
      ablation.
AB  - INTRODUCTION: The dromotropic effects of intracardiac parasympathetic nerve
      stimulation have not been well studied; furthermore, the effects of
      radiofrequency ablation lesions on parasympathetic nerve stimulation are not
      clear. METHODS AND RESULTS: Group I: intracardiac electrical stimulation in the
      right posteroseptal and anteroseptal areas under different stimulation strengths;
      group II: intracardiac electrical stimulation before and 10 minutes after
      intravenous propranolol; group III: intracardiac electrical stimulation before
      and 5 minutes after intravenous atropine. Among the 10 patients with AV nodal
      reentrant tachycardia (group IV) and the 10 patients with atrial flutter (group
      V), atrial fibrillation was induced before and after successful ablation, and
      intracardiac electrical stimulation in the right posteroseptal area was performed
      before and after successful ablation. The maximal response and complete decay of
      the response occurred within 2 to 6 seconds of initiation or termination of
      parasympathetic nerve stimulation. This negative dromotropic effect disappeared
      after atropine was administered, but not after propranolol. After successful
      ablation, parasympathetic stimulation still induced negative dromotropic effects.
      CONCLUSION: Electrical stimulation of parasympathetic nerve fibers near the
      posteroseptal and anteroseptal areas could induce a negative dromotropic effect,
      and this effect was preserved after successful radiofrequency ablation of slow
      pathway and isthmus conduction.

PMID- 9554730
TI  - Influence of filtering techniques on the time-domain analysis of signal-averaged
      P wave electrocardiogram.
AB  - INTRODUCTION: The advent of signal-averaged ECG (SAECG) systems for P wave
      analysis has made it important to determine if the use of different filtering
      techniques in these systems is diagnostically equivalent. METHODS AND RESULTS:
      Three different high-pass filtering techniques and two cutoff frequency values
      were used: 29- and 40-Hz Butterworth bidirectional filter (BB29, BB40), 29- and
      40-Hz Butterworth unidirectional filter (UB29, UB40), and 29- and 40-Hz least
      mean square filter (LMS29, LMS40). Normal healthy volunteers (n = 36) and
      patients with documented paroxysmal atrial fibrillation (n = 23) were analyzed. A
      custom-built SAECG system and standard bipolar orthogonal leads were used. Noise
      was reduced to < 0.3 microV. P wave total duration, root mean square voltage of
      the terminal 20, 30, and 40 msec of the filtered vector magnitude, and the area
      under the curve between the onset and offset of averaged unfiltered and filtered
      P wave vector magnitude were analyzed. Only the duration of the P wave showed
      statistically significant differences between groups, being longer in the PAF
      group for all filters and cutoff frequencies studied. A bias increment of
      approximately 20 msec was detected in unidirectional and least mean square
      filters as compared to the bidirectional filter. Sensitivity, specificity, and
      predictive accuracy were > 70% for all filters; the BB40 filter yielded the best
      performance. CONCLUSION: The normality limits derived from one filter cannot be
      applied directly to recordings obtained from the other filters. Critical limits
      must be established individually for different software settings.

PMID- 9554731
TI  - Enhanced detection criteria in implantable defibrillators.
AB  - INTRODUCTION: Enhanced detection criteria in third-generation implantable
      defibrillators have been implemented to avoid inappropriate therapy of fast
      supraventricular arrhythmias. We prospectively analyzed the use of these criteria
      in patients with an implantable defibrillator with electrogram storing
      capability. METHODS AND RESULTS: In 82 consecutive patients with a Guidant-CPI
      implantable defibrillator, sudden onset > 9% and stability < 40 msec were
      systematically programmed in zone 1 of therapy together with a sustained rate
      duration security mechanism. All detected tachycardia episodes were analyzed. The
      study population consisted of 59 patients who had at least one episode of
      tachycardia detected in zone 1 during follow-up. The tachycardia rate in zone 1
      never exceeded 210 beats/min. Twenty patients had no episodes during follow-up,
      and three patients had episodes detected exclusively in zone 2 of therapy.
      Supraventricular arrhythmias were detected frequently in the ventricular
      tachycardia zone (193 of 690 tachycardia episodes in 23 of 59 patients). Use of
      sudden onset was very effective in detecting sinus tachycardias (65 of 67
      episodes), and stability was very useful in detecting atrial fibrillation (31 of
      32 episodes). However, sensitivity in detecting ventricular tachycardia was only
      90% (451 of 497 episodes). Application of the sustained rate duration criterion
      allowed appropriate treatment of all ventricular tachycardia episodes, increasing
      sensitivity to 100%; however, specificity in appropriate nontreatment of
      supraventricular decreased from 96% to 83%. Subsequent analysis of different
      algorithms applied to our data showed that sudden onset > 9% and stability < 40
      msec was the algorithm with the best specificity and sensitivity. CONCLUSION:
      Programming sudden onset and stability detection criteria with a sustained rate
      duration safety net for triggering tachycardia therapy results in appropriate
      device management in most patients with supraventricular and slow (< 210
      beats/min) ventricular tachycardias.

PMID- 9554732
TI  - Changes in cardiac repolarization following short periods of ventricular pacing.
AB  - INTRODUCTION: "Cardiac memory" (primary T wave change) is thought to occur after
      15 minutes to several hours of right ventricular (RV) pacing. The two components
      of the temporal change in repolarization are memory and accumulation. The purpose
      of this study was to examine quantitatively the effect of short periods of
      ventricular pacing on the human cardiac action potential, using monophasic action
      potential (MAP) recordings. METHODS AND RESULTS: Thirty-one patients (ages 43+/
      14 years) with structurally normal hearts undergoing a clinically indicated
      electrophysiologic procedure were enrolled. Catheters were placed in the right
      atrium (RA) and RV, and a MAP catheter was positioned at the RV septum. APD90 was
      calculated from digitized MAP recordings. MAP morphology comparisons were
      performed using the root mean square (RMS) of the difference between complexes.
      All pacing was at 500-msec cycle length. There were four pacing protocols: (1) RA
      pacing was performed for approximately 15 minutes to evaluate temporal stability
      of the MAP recordings (5 pts); (2) to evaluate the memory phenomenon, four
      successive 1-minute episodes of RV pacing were interspersed with 2 minutes of RA
      pacing (5 pts); (3) the accumulation phenomenon was evaluated by assessing the
      effects of 1, 5, 10, and 15 minutes of RV pacing on the MAP during RA pacing (16
      pts); and (4) 20 minutes of RV pacing was followed by 10 minutes of RA pacing to
      correlate visually apparent T wave changes with changes in MAP recordings (5
      pts). In the control patients, no changes in APD90 or RMS analysis were noted
      during 14.9+/-1.4 minutes of RA pacing. In the second protocol, RMS of the
      difference between the baseline MAP complexes and the signal average of the first
      50 beats following each of four 1-minute RV pacing trains demonstrated
      progressively greater differences in morphology after successive episodes of RV
      pacing. In protocol 3, RMS analysis identified a progressively greater difference
      between the baseline MAP recording and the average of the first 50 beats after 1,
      5, 10, and 15 minutes of RV pacing. In protocol 4, visually apparent changes in T
      waves occurred in parallel with the RMS of the difference between the baseline
      MAP recordings and the average of the first 50 beats after 20 minutes of RV
      pacing. Similar changes also were demonstrated by APD90 analysis. CONCLUSION:
      This study is the first to demonstrate that episodes of abnormal ventricular
      activation as short as 1 minute in duration may exert lingering effects on the
      repolarization process once normal ventricular activation resumes.

PMID- 9554733
TI  - Mechanisms of induction of typical and reversed atrial flutter.
AB  - INTRODUCTION: Typical flutter is due to reentry around caval veins and terminal
      crest. In patients with typical flutter, reversed (clockwise) reentry can be
      induced. We studied mechanisms of typical and reversed flutter induction. METHODS
      AND RESULTS: Thirteen patients (11 men) underwent 16 radiofrequency (RF) ablation
      procedures for typical (12) or reversed flutter (1). High right atrium (RA)
      stimulation included 1 to 3 extrastimuli over cycle lengths 600 to 250 msec, and
      burst. We recorded simultaneously from three levels of septal and anterior RA. RF
      was delivered to the inferior vena cava-tricuspid isthmus (CTI). Of 25
      inductions, 4 were a result of single, 9 double, and 11 triple extrastimuli, and
      1 burst. Clinical basal flutter was induced (7 typical, 1 reversed). After RF,
      typical flutter was reinduced in 9 cases and reversed flutter in 7, with only
      typical flutter seen clinically. All flutters were interrupted by ablation or
      catheter pressure on the CTI. Typical flutter began by low RA septal activation
      block, preceded by repetitive responses in 12 instances, atypical flutter in 1,
      and directly from stimuli in 4. Reversed flutter started in 8 instances by low RA
      block of a stimulated front descending the anterior wall and in 1 by repetitive
      responses. CONCLUSION: Septal activation block was the usual mechanism of typical
      flutter induction by RA extrastimuli. Facilitation of reversed flutter after RF
      application is probably due to a new area of block in the CTI. Flutter induction
      without intermediate rhythms confirms the presence of block at the terminal crest
      at baseline.

PMID- 9554735
TI  - Reduced inward rectifying and increased E-4031-sensitive K+ current density in
      arrhythmogenic subendocardial purkinje myocytes from the infarcted heart.
AB  - INTRODUCTION: Subendocardial Purkinje myocytes from the 48-hour infarcted heart
      (IZPCs) have reduced resting potentials, possibly due to altered inwardly
      rectifying K+ currents IK1. Abnormal depolarization-activated outward K+ currents
      could contribute to long triangularly shaped action potentials of IZPCs. METHODS
      AND RESULTS: We used whole cell patch recordings to compare cesium-sensitive IK1
      and 4-aminopyridine (4-AP)-resistant, noninactivating sustained IK between normal
      Purkinje myocytes (NZPCs) and IZPCs. IZPCs showed decreased net membrane
      currents. Two IZPC groups were distinguished, based on 4-AP-resistant outward K+
      currents. IZPC-I had isochronal IK1 current-voltage relations similar to NZPCs
      whereas IZPC-II showed significantly reduced IK1 and increased outward plateau
      currents. To study the sustained IK in the presence of the Class III
      antiarrhythmic agent E-4031, a two-pulse protocol was used to inactivate
      transient outward currents, followed by step depolarizations. E-4031-sensitive
      currents were significantly greater in IZPCs at depolarized potentials (> 0 mV).
      Similar to NZPCs, IZPC E-4031 currents showed time dependence during
      depolarization, lack of rectification at positive steps, and voltage-dependent
      recovery from block. CONCLUSION: Decreased IK1 may account for reduced resting
      potentials in IZPCs. E-4031-sensitive currents in NZPCs, unlike those in canine
      ventricular myocytes, are sensitive to 4-AP and are larger in IZPCs.

PMID- 9554734
TI  - Differential role of epicardial and endocardial K(ATP) channels in potassium
      accumulation during regional ischemia induced by embolization of a coronary
      artery with latex.
AB  - INTRODUCTION: K(ATP) channels are activated predominantly in the epicardium
      during regional ischemia. Therefore, the role of K(ATP) channels in ischemia
      induced rise of extracellular potassium concentration ([K+]o) might be greater in
      the epicardium. METHODS AND RESULTS: In 18 anesthetized dogs, the left anterior
      descending coronary artery (LAD) was ligated, followed by injection of 23-microm
      latex beads into the occluded artery to interrupt collateral flow, by which
      accumulated [K+]o might wash out. Epicardial and endocardial [K+]o were measured
      during a 20-minute period of ischemia using a valinomycin membrane. The dogs were
      divided into three groups: 6 control dogs (CTRL); 7 dogs pretreated with
      intravenous glibenclamide (0.3 mg/kg [GLIB]), a blocker of K(ATP) channels; and 5
      dogs pretreated with intravenous nicorandil (0.2 to 0.25 mg/kg [NCR]), a K(ATP)
      channel opener. Before LAD occlusion, there was no difference in [K+]o among the
      three groups. In the control group, epicardial and endocardial [K+]o were
      increased to a similar level as a function of time after occlusion (CTRL) at both
      layers. Ischemia-induced epicardial [K+]o rise was suppressed by GLIB (8.4+/-0.4
      vs 6.7+/-0.5 mM, P < 0.05) but augmented by NCR (12.9+/-2.0 mM, P < 0.05). In
      contrast, endocardial [K+]o rise remained unaffected (7.6+/-0.2 mM CTRL, 7.6+/
      1.3 mM GLIB, and 9.4+/-2.2 mM NCR, P = NS). CONCLUSION: Activation of K(ATP)
      channels plays an important role in epicardial [K+]o rise, but not in endocardial
      [K+]o rise, during regional ischemia. Another mechanism(s) may be important for
      endocardial [K+]o accumulation.

PMID- 9554737
TI  - AV nodal reentrant tachycardia with unusual characteristics: lessons from
      radiofrequency catheter ablation.
AB  - There are still some AV nodal reentrant tachycardias with unusual AV nodal
      properties that need further study to understand these complexities. Accordingly,
      the two-dimensional model with alpha and beta pathways in the AV nodal reentrant
      tachycardia circuit certainly is an oversimplification and does not explain
      adequately the anatomic and physiologic complexity of the AV junctional area. The
      modern concept suggests that this arrhythmia takes place in a highly complex
      three-dimensional model with nonuniform anisotropy and discontinuous conduction
      property in the AV junctional area. Application of radiofrequency energy within
      the AV junctional area should always be performed carefully to achieve a
      successful ablation procedure and to minimize possible injury of AV nodal
      conduction.

PMID- 9554736
TI  - Lidocaine's effect on defibrillation threshold are dependent on the
      defibrillation electrode system: epicardial versus endocardial.
AB  - INTRODUCTION: Epicardial and endocardial defibrillation electrode systems affect
      myocardial electrophysiology and sympathetic function differently. Thus, we
      postulate that antiarrhythmic drugs will interact with these electrode systems
      differently. METHODS AND RESULTS: Defibrillation energy requirements (DER) at 20%
      (ED20), 50% (ED50), and 80% (ED80) success were measured at baseline and during
      lidocaine (10 mg/kg per hour) or D5W treatment for epicardial and endocardial
      electrodes. Pigs were randomized to treatment (lidocaine or D5W) and electrode
      system, which resulted in four experimental groups: (1) epicardial electrode +
      D5W; (2) epicardial electrode + lidocaine; (3) endocardial electrode + D5W; and
      (4) endocardial electrode + lidocaine. ED50 DER (mean +/- SEM) values at baseline
      for groups 1-4 were 10.6+/-1, 8.5+/-1, 12.6+/-1, and 12.3+/-1 J, respectively.
      DER values for groups 1 and 3 during D5W were similar to baseline. Conversely,
      lidocaine increased ED50 DER values from 8.5+/-1 to 13.5+/-2 J (P < 0.05) in
      group 2 animals (epicardial electrodes). When lidocaine was administered to group
      4 animals (endocardial electrodes), however, ED50 DER values remained similar to
      baseline values (12.3+/-1 to 14.3+/-2 J, P = NS). Lidocaine increased ED50 DER
      values by 59% with the epicardial electrode system, which was significantly
      greater than the 16% increase with the endocardial electrode system (P < 0.05).
      Electrophysiologic response and electrode impedance were similar between
      electrode systems. CONCLUSION: Lidocaine increases DER values to a greater extent
      when using epicardial versus endocardial electrode system. Thus, drug-device
      interactions are dependent on the electrode system. These data suggest that the
      electrophysiologic milieu created by endocardial defibrillation mitigates the
      effects that lidocaine has on DER values.

PMID- 9554738
TI  - Atrial tachycardia in a patient with tricuspid atresia and Fontan surgery.

PMID- 9554739
TI  - The morphology of the atrial approaches to the AV node.

PMID- 9554740
TI  - In vitro mutations in dihydrofolate reductase that confer resistance to
      methotrexate: potential for clinical application.
AB  - Mammalian cells cultured in the presence of the chemotherapeutic agent,
      methotrexate, develop resistance to this drug. Sometimes this is due to mutations
      in the gene for dihydrofolate reductase, the primary target of methotrexate.
      However, it has not been possible to link such polymorphism to resistance of
      neoplastic disease to therapy with methotrexate. Nevertheless, interest in this
      possibility lead to the introduction of many mutations into the cDNA for human
      DHFR by mutagenesis. Most of the corresponding enzyme variants have been
      expressed in Escherichia coli and characterized. Many mutations in codons for
      hydrophobic residues at the active site greatly decrease inhibition by
      methotrexate, and by the related substrate analogue, trimetrexate, while allowing
      the retention of considerable catalytic efficiency. Introduction of some of these
      mutants into mammalian cells by retroviral transfer provides substantial
      protection from toxic effects of the inhibitors, and has promise for the
      myeloprotection of patients receiving therapy with methotrexate or trimetrexate.
      Another potential use is in therapy for inherited disorders of hematopoiesis,
      where genetic modification of enough cells is a perennial problem. After
      transplantation of bone marrow that has been transduced with a bicistronic vector
      encoding both the mutant DHFR and a therapeutic gene, subsequent administration
      of methotrexate or trimetrexate should permit selection and enrichment of
      genetically modified hematopoietic cells.

PMID- 9554741
TI  - Common ancestral mutation in the MEN1 gene is likely responsible for the
      prolactinoma variant of MEN1 (MEN1Burin) in four kindreds from Newfoundland.
AB  - Familial multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
      disorder with affected individuals developing parathyroid, gastrointestinal (GI)
      endocrine, and anterior pituitary tumors. Four large kindreds from the Burin
      peninsula/Fortune Bay area of Newfoundland with prominent features of
      prolactinomas, carcinoids, and parathyroid tumors (referred to as MEN1Burin) have
      been described, and they show linkage to 11q13, the same locus as that of MEN1.
      Haplotype analysis with 16 polymorphic markers now reveals that representative
      affected individuals from all four families share a common haplotype over a 2.5
      Mb region. A nonsense mutation in the MEN1 gene has been found to be responsible
      for the disease in the affected members in all four of the MEN1Burin families,
      providing convincing evidence of a common founder.

PMID- 9554742
TI  - Seven novel mutations in mut methylmalonic aciduria.
AB  - Methylmalonic aciduria (MMA) is an autosomal recessive inborn error of metabolism
      that results from functional defects in methylmalonyl CoA mutase (MCM), a nuclear
      encoded, mitochondrial enzyme that uses the vitamin B12 derivative,
      adenosylcobalamin (AdoCbl) as a cofactor. To date, 23 mutations have been
      identified at the MUT locus on the short arm of chromosome 6, causing the mut
      forms of MMA (mut complementation group; mut MMA, McKusick #251000). We now
      report seven novel mutations. Three were found inmut0 patients: R228Q (c759G-->A)
      was found as a heterozygous change; G312V (c1011G-->T) and 346delL (c1112delCTT)
      were both found as homozygous changes. Four mutations were found in mut patients:
      A191E (c648C-->A) and V633G (c1974T-->G) were found in the same patient; 684insL
      (c2128insCTC) and L685R (c2130T-->G) were both found as homozygous changes. The
      recent modelling of the human methylmalonyl CoA mutase allowed for an
      interpretation of the identified mutations.

PMID- 9554743
TI  - Identification of three novel mutations and a high frequency of the Arg778Leu
      mutation in Korean patients with Wilson disease.
AB  - Four mutations--R778L, A874V, L1083F, and 2304delC--in the copper-transporting
      enzyme, P-type ATPase (ATP7B), were identified in Korean Patients with Wilson
      disease. Arg778Leu, the most frequently reported mutation of this enzyme, was
      found in six of eight unrelated patients studied, an allele frequency of 37.5%,
      which is considerably higher than those in other Asian populations. The novel
      single nucleotide deletion, 2304delC, was found in one patient. Since a mutation
      at cDNA nucleotide 2302 (2302insC) had been previously described, this region of
      the ATP7B gene may be susceptible to gene rearrangements causing Wilson disease.

PMID- 9554744
TI  - Homozygous nonsense mutation in helix 2 of K14 causes severe recessive
      epidermolysis bullosa simplex.
AB  - We have studied a consanguineous family containing two children with severe,
      generalized epidermolysis bullosa simplex (EBS). Electron microscopy of skin
      biopsies from the affected individuals showed that basal keratinocytes were
      devoid of tonofilament bundles, although some single intermediate filament were
      visible. Genetic linkage analysis with the microsatellite probe D12S96 excluded
      the type II keratin gene cluster in this family. However, homozygosity by descent
      was observed with the polymorphic probes KRT9, KRT10 Ava II, and D17S1787 in both
      affected children, consistent with a recessive defect in a type I keratin.
      Immunoreactivity to keratin K5 and K15 was normal, but monoclonal antibodies
      LL001 and RCK107 against K14 showed no staining, suggesting a deficiency of K14
      in these individuals. mRNA extracted from biopsy material was amplified by RT-PCR
      to obtain full-length K14 cDNA. Direct automated sequencing identified a
      homozygous nonsense mutation, W305X. A Hinf I restriction enzyme site is created
      by this nucleotide transition, which was used to confirm the presence of the
      mutation in this kindred and exclude it from 100 normal chromosomes. This is the
      fourth kindred with severe recessive EBS for whom a mutation has been found in
      the K14 gene. In this instance, the premature termination codon is the farthest
      downstream of the reported cases, occurring in the helix 2 domain and so giving a
      much longer translation product. Nevertheless, the heterozygous carriers are
      unaffected by the disease and display no epidermal fragility. We postulate that
      translation of the potentially dominant-negative truncated K14 might be down
      regulated due to instability of the mutant mRNA, as observed in previous cases
      with similar mutations.

PMID- 9554745
TI  - Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic
      telangiectasia reveals null alleles.
AB  - Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder
      characterized by multisystemic vascular dysplasia and recurrent hemorrhage from
      the sites of vascular lesions. Two genes have been identified for HHT. Endoglin,
      a TGF-beta binding protein which maps to chromosome 9q3, is the gene for HHT1.
      The type and location of most of the previously described mutations in the
      endoglin (ENG) gene suggested a dominant-negative model of receptor-complex
      dysfunction for the molecular basis of this disorder. In this article we describe
      11 novel ENG mutations in HHT kindreds, which include missense and splice-site
      mutations. Two identical missense mutations in unrelated families disrupt the
      start codon of the gene. In addition, some frameshift and nonsense mutations lead
      to very low or undetectable levels of transcript from the mutant allele. These
      combined data suggest that the nature of most ENG mutations is to create a null
      (nonfunctional) allele, and that there is no requirement for the synthesis of a
      truncated endoglin protein in the pathogenesis of HHT.

PMID- 9554746
TI  - Molecular analysis and clinical findings in the Spanish Gaucher disease
      population: putative haplotype of the N370S ancestral chromosome.
AB  - Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in
      the lysosomal beta-glucocerebrosidase (GBA) gene. As the disease is particularly
      prevalent among Ashkenazi Jews, most studies have been carried out on this ethnic
      group. In the current study, we present a mutation analysis of the GBA gene in
      Spanish patients together with the clinical findings. We conducted a systematic
      analysis in 53 unrelated GD patients. The GBA gene was initially scanned for nine
      previously described mutations by ASO hybridization or restriction analysis after
      PCR amplification. The remaining unidentified alleles were screened by
      nonisotopic PCR-SSCP analysis and sequenced. This approach allowed the
      identification of 101 of 106 GD alleles (95.3%) involving 24 different mutations,
      11 of which are described for the first time: G113E (455G-->A), T134P (517A-->C),
      G389E (1283G-->A), P391L (1289C-->T), N392I (1292A-->T), Y412H (1351T-->G), W(
      4)X (108G-->A), Q169X (662C-->T), R257X (886C-->T), 500insT, and IVS5+1G-->T.
      Most mutations are present in one or few GD chromosomes. However, two mutations,
      N370S (1226A-->G) and L444P (1448T-->C), are very frequent and account for 66.1%
      of the total number of alleles. Linkage disequilibrium was detected between these
      two mutations and an intragenic polymorphism, indicating that expansion of
      founder alleles occurred in both cases. Analysis of several microsatellite
      markers close to the GBA gene allowed us to establish the putative haplotype of
      the ancestral N370S chromosome.

PMID- 9554747
TI  - Frequent mutation in Chinese patients with infantile type of GSD II in Taiwan:
      evidence for a founder effect.
AB  - Glycogen storage disease type II (GSD II, Pompe's disease), an autosomal
      recessive inherited disease, is caused by the deficiency of acid alpha-D
      glucosidase, which results in the impaired glycogen degradation in lysosome and
      causes excess glycogen accumulation in lysosome. In Taiwan, the infantile form of
      GSD II is the most common type of glycogen storage diseases. The frequency of
      C1935A mutant allele is 0.8 in these Chinese patients. In this study, we analyzed
      four single point polymorphic markers (324, 1203, 2065, 2338) by ACRS-based RFLP
      We observed that the alleles possessing the C1935A mutation in 19 of 25 Chinese
      patients who were heterozygous or homozygous have conserved polymorphic markers,
      and all of C1935A mutant alleles in these patients are linked to a specific
      haplotype. The allele frequency of this specific haplotype in 19 Chinese patients
      and in 42 normal individuals is 0.95 and 0.17, respectively (P<0.005, chi2 =
      66.018). This result suggests that the C1935A mutation in Chinese patients with
      infantile form of GSD II is due to the founder effect.

PMID- 9554748
TI  - Identification of molecular defects in Italian Sanfilippo A patients including 13
      novel mutations.
AB  - Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) is a
      lysosomal storage disorder caused by the deficiency of the enzyme heparin
      sulfamidase (EC 3.10.1.1), required for the degradation of the mucopolysaccharide
      heparan sulfate. Patients develop central nervous system degeneration resulting
      in progressive dementia, developmental delay, hyperactivity, and aggressive
      behaviour; subjects may present a wide spectrum of clinical severity. Here, we
      report the results from molecular analysis of 24 Italian MPS IIIA patients
      diagnosed over the last 15 years in our laboratory. Altogether, we were able to
      characterize 38 out of the 48 (79%) pathogenic alleles. We identified 16
      molecular defects, 13 novel. The majority of alterations were missense mutations:
      on exon two (Y40N; A44T; S66W; R74C), on exon four (G122R; P128L; L146P; R150Q),
      on exon five (D179N; R182C), on exon six (P227R) and on exon eight (E369K;
      R377C). Single base pair deletions: on exon two (A52nt-1) and on exon eight
      (T360nt-1) and one base pair insertion on exon eight (V361nt+1) were also
      identified. Restriction enzyme or ARMS analyses were used to confirm each
      alteration. S66W represents the most common alteration in our patients population
      accounting for 33% of the total alleles. Interestingly, all six patients from
      Sardinia present this mutation, and five of them are homozygous for this change,
      suggesting that these subjects may have been derived from a common founder.

PMID- 9554749
TI  - Clustering of private mutations in the congenital chloride diarrhea/down
      regulated in adenoma gene.
AB  - An inherited defect in intestinal anion exchange, congenital chloride diarrhea
      (CLD), was recently shown to be caused by mutations in the down-regulated in
      adenoma (DRA) gene. A three base pair deletion resulting in the loss of an amino
      acid valine (V317del) in the predicted CLD/DRA protein was shown to be
      responsible for all CLD cases in a Finnish founder population. Two additional
      mutations, H124L and 344delT, were found in Polish CLD patients. Here, we
      screened for additional mutations in a set of 14 CLD families of Polish, Swedish,
      North American, and Finnish origin using primers that allowed mutation searches
      directly from genomic DNA samples. We found eight novel mutations in the CLD/DRA
      gene. The mutations included two transversions, one transition, one insertion,
      and four small deletions. Of 11 sequence alterations detected so far, nine lie
      clustered in three short segments that are 49 bp, 39 bp, and 65 bp in size,
      respectively. These short segments span only 6.7% of the total cDNA length,
      suggesting functional importance or mutation-prone DNA regions of the
      corresponding CLD/DRA protein domains.

PMID- 9554750
TI  - Identification of a novel point mutation (S65T) in alpha-galactosidase A gene in
      Chinese patients with Fabry disease. Mutations in brief no. 169. Online.
AB  - Fabry disease is an X-linked inborn error of sphingolipid catabolism resulting
      from deficient enzyme activity of alpha-galactosidase A. The molecular defects of
      human alpha-galactosidase A gene causing Fabry disease have been characterized,
      including gene rearrangement and point mutations, which show the genetic
      heterogeneity in Fabry disease. To characterize the molecular defects of these
      patients, each exon of alpha-galactosidase A gene including intron-exon junctions
      were PCR amplified using biotin-labelled primer and sequenced using magnetic
      beads solid-phase sequencing. A G to C transversion was identified in the last
      nucleotide of exon 1 in two unrelated Chinese patients. This mutation obliterates
      an EcoN1 restriction site. Family studies show close linkage with the affected
      family members. Screening of 100 alleles (22 males, 39 females) of unrelated
      normal Chinese can not find this mutation. This mutation not only changes the
      amino acid from serine to threonine, but also likely cause splicing defects. To
      our knowledge, this is the first report of mutation in Chinese patients with
      Fabry disease, and a novel mutation causing Fabry disease not reported in
      literature previously.

PMID- 9554751
TI  - A novel lysosomal acid lipase gene mutation in a patient with cholesteryl ester
      storage disease.
AB  - The molecular defects in the gene encoding the lysosomal acid lipase (LAL) were
      investigated in an adult male patient affected with cholesteryl ester storage
      disease (CESD), an autosomal recessive disorder associated with LAL deficient
      activity. Nucleotide sequencing of amplified LAL genomic DNA or reverse
      transcribed mRNA demonstrated that this patient was a compound heterozygote for a
      previously reported mutation, a G-->A transition at position -1 of the exon 8
      splice donor site, resulting in skipping of the complete exon 8, and for a C-->T
      substitution at position 233 (exon 3), which introduces a premature in-frame
      termination codon. This yet undescribed mutation, which results in the loss of
      89% of LAL amino acids, is very likely to abolish the LAL catalytic activity.

PMID- 9554752
TI  - A novel single basepair insertion in exon 6 of the Bruton's tyrosine kinase (Btk)
      gene from a Japanese X-linked agammaglobulinemia patient with growth hormone
      insufficiency.
AB  - A novel insertion mutation in exon 6 of the Btk gene was detected in a 17 year
      old XLA patient with GH insufficiency. We synthesized cDNA from leukocyte total
      RNA and amplified every region of the Btk-coding sequence. Sequencing of cDNA
      fragments revealed a single basepair insertion mutation at codon 157 in exon 6
      (CAG-->CAAG) which leads to premature termination at codon 193 in exon 7. To
      confirm the results, we also performed a PCR-DdeI digestion analysis using
      leukocyte genomic DNA. The PCR product from the patient's genomic DNA was
      uncleaved with DdeI, as expected. PCR-DdeI digestion analysis of the family
      members showed that the mother and elder sister were carriers with the mutation
      and that the younger sister did not carry the mutation.

PMID- 9554753
TI  - Identification of a novel mutation (S13F) in the CFTR gene in a CF patient of
      Sardinian origin.
AB  - In this paper, we describe a novel CF mutation consisting in a C-->T substitution
      at nucleotide 170 in exon 1 of CFTR gene, converting a serine residue into
      phenylalanine at position 12 (S13F) of the CFTR protein. This mutation was
      detected in a single patient of Sardinian descent in compound heterozygosity with
      T338I, who presented at 9 years of age with hyponatremic dehydration associated
      with hypochloremia, hypokaliemia and metabolic alkalosis. Sweat chloride values
      were 120 mmol/l. Now the patient is 11 years old and has not shown so far any
      pancreatic or lung involvement. The serine to phenylalanine substitution is a non
      conservative change, replacing a non polar for a polar amino acid residue and
      therefore is most likely a disease-causing mutation.

PMID- 9554755
TI  - An androgen receptor gene mutation (A645D) in a boy with a normal phenotype.
AB  - Over 100 mutations have so far been published in the androgen receptor gene (AR)
      in patients with different degrees of undervirilisation. The AR gene consists of
      8 exons, exons 2-3 code for the DNA binding domain and exons 4-8 (codon 628-919)
      for the steroid binding domain (codon 667-919). Only four mutations have been
      published in the 5' end of exon 4, codons 628-667, that is in two PAIS cases and
      two prostate tumours. In a set of phenotypically normal controls we observed one
      mutation in exon 4, codon 645, in a 15 year old boy. He has a history of Wilms'
      tumour but no undervirilisation and without a family history with intersex. Exon
      4 was amplified from constitutional DNA and subject to DGGE with 35-65% of
      denaturants. Aberrant fragments were subject to a new PCR and direct sequencing
      was performed. This mutation changed Ala645-->Asp due to change of GCT-->GAT This
      was not detected in 108 normal chromosomes. Interestingly, the same mutation was
      recently reported in one PAIS case. This phenotypic discrepancy calls for
      functional studies of this region. This is the first case of a normal phenotype
      with an amino acid alteration in the AR gene.

PMID- 9554754
TI  - A new missense substitution at a mutational hot spot of the androgen receptor in
      siblings with complete androgen insensitivity syndrome.
AB  - Several mutations have been described in the human androgen receptor gene
      including constitutional mutations in androgen insensitivity syndrome, somatic
      mutations in prostate cancer and triplet expansions in Kennedy's disease
      (Gottlieb et al. 1997). Here we report on two siblings with complete androgen
      insensitivity and a novel missense mutation, D695V, in their androgen receptor
      gene. The two XY females are siblings of German descent and presented at the ages
      of 23 and 19 years, respectively, with typical clinical features of complete
      androgen insensitivity. We found both siblings to be hemizygous for a new adenine
      to thymine transversion at the second nucleotide of codon 695 within the fourth
      exon of the human androgen receptor gene. The resulting missense mutation D695V
      is located at the amino-terminal border of the ligand-binding domain of the
      androgen receptor. The aspartic acid residue at this position is highly conserved
      in the steroid binding domains of other members of the nuclear receptor family
      and has already been found to be the site of two other missense mutations
      associated with androgen insensitivity syndrome (Ris Stalpers et al. 1991, Hiort
      et al. 1996). Three of four reported subjects showed the complete androgen
      insensitivity phenotype, in accordance with the two siblings in our study. We
      suggest that the existence of three pathological amino acid substitutions for
      aspartic acid 695 most likely reflects the essential role of this residue for
      normal androgen receptor function in male sexual differentiation.

PMID- 9554757
TI  - A Dde I RFLP in exon 21 of human EL1 gene, encoding protein 4.1, detectable by
      SSCP.
AB  - Protein 4.1 is a major component of the junctional complex at the red cell
      skeleton. Genomic studies have recently evidenced that the encoding gene (EL1
      locus) is present in a single copy per haploid genome. Several RFLPs have already
      been characterized within intron sequences. Here, we describe the first RFLP
      found within the coding sequence. This polymorphism (C or T at position 2723, in
      exon 21) does not affect the amino acid sequence (Thr-->Thr). It can be detected
      by either Dde I restriction digestion of an appropriate PCR product, or simply by
      SSCP These findings should facilitate analysis of families with 4.1 deficiencies
      causing hereditary elliptocytosis.

PMID- 9554756
TI  - Familial Kallmann syndrome: a novel splice acceptor mutation in the KAL gene.
AB  - Kallmann syndrome is an inherited disease which is characterised by anosmia
      (inability to smell) and hypogonadotropic hypogonadism both of which are thought
      to occur as a result of a failure of correct neuronal migration. To date the only
      genetic lesions identified are mutations in the X-linked gene, KAL. We conducted
      a mutation screen of the KAL gene in a family with Kallmann syndrome. This
      identified a new mutation in the KAL gene which removed an acceptor site at the
      junction of exon 6/intron 5. Exon 6 of the KAL gene encodes the C-terminal
      portion of a fibronectin type III domain may be involved in axonal pathfinding.
      We presume that the described mutation would result in the removal of exon 6
      resulting in a frame shift which terminates the protein prematurely. It has been
      proposed that both mental illness and vesico-ureteric reflux are associated with
      mutations in the KAL gene. However, results from the family presented here do not
      show an association between either trait and the KAL gene mutation.

PMID- 9554758
TI  - Novel DNA sequence differences in the beta2-adrenergic receptor gene promoter
      region.

PMID- 9554759
TI  - Real-time measurement of skin radiation during cardiac catheterization.
AB  - A novel skin dose monitor was used to measure radiation incident on maximal X-ray
      exposed skin during 135 diagnostic and 65 interventional coronary procedures. For
      the diagnostic studies (n = 135), mean skin dose was 180 +/- 64 mGy; for PTCA (n
      = 35), it was 1021 +/- 674 mGy, single stents (n = 25) 1529 +/- 601 mGy, and
      multiple stents with rotational atherectomy (n = 5) 2496 +/- 1028 mGy. The dose
      independently increased with more cine runs, more fluoroscopy, and greater
      patient weight. Physicians should consider the potential for adverse radiation
      exposure when planning coronary interventional cases and deciding on the X-ray
      mode and angles used.

PMID- 9554760
TI  - Use of assumed versus measured oxygen consumption for the determination of
      cardiac output using the Fick principle.
AB  - Assumed oxygen consumption (VO2) is increasingly used as a convenient surrogate
      for measured VO2 for calculation of cardiac output. This substitution is often
      based on empirical formulae, previously validated only in relatively young
      patients. To assess the inaccuracy introduced by extrapolating these formulae to
      older patients, we compared measured VO2 with assumed VO2 in 57 patients. VO2 was
      measured using an open circuit analyzer. Assumed VO2 was calculated according to
      the LaFarge or Bergstra formulae. Agreement between both methods was assessed
      according to the method of Bland and Altman. The mean difference of measured VO2
      minus assumed VO2 was 7.9 ml/min/m2 (P < 0.02) using the LaFarge formula, and 
      15.6 ml/min/m2 (P < 0.0002) using the Bergstra formula across a range of measured
      VO2 from 70 to 176 ml/min/m2. A systematic error was introduced by assumed VO2
      from both formulae of underestimating higher and overestimating lower values of
      VO2, resulting in poor overall agreement with measured VO2. The same error and
      poor agreement was found when analyzing subgroups of patients > or =60 or <70
      years of age. In summary, use of assumed VO2 introduces large, unpredictable
      errors in adult patients, suggesting requirement for measurement of VO2 when
      calculating cardiac output.

PMID- 9554761
TI  - Efficacy and safety of early coronary stenting for unstable angina.
AB  - To determine the efficacy and safety of early coronary stenting for unstable
      angina, we studied 91 consecutive patients with unstable angina. Thirty-one
      patients underwent stenting 72 h or more after admission, and another 60 patients
      underwent stenting within 72 h of admission. The clinical and angiographic follow
      up had been done for 6 mo. There were no differences between the baseline
      clinical and angiographic characteristics of both groups. The maximum balloon
      pressure was higher (14.1 +/- 1.2 vs. 12.6 +/- 0.9, P < 0.01) and the hospital
      stay was shorter (9.7 +/- 2.7 vs. 18.7 +/- 5.8 d, P < 0.0001) in the early
      stenting group. These two groups were similar in the clinical success rate (90.0%
      vs. 93.5%), without any abrupt closure, subacute thrombosis, death, myocardial
      infarction, or coronary bypass surgery. These findings indicate that early
      stenting can be useful in patients with unstable angina.

PMID- 9554762
TI  - Comparison of the sheath delivery system versus bare stenting for coronary stent
      implantation.
AB  - Outside the United States, Palmaz-Schatz coronary stents are implanted by hand
      crimping the stent to a high pressure balloon without the use of a protective
      sheath. This lowers the delivery profile, increases the ease of deployment, and
      ensures that the postdilatation balloon is centered on the stent. To assess this
      bare stenting technique, 209 patients were retrospectively analyzed: 92 patients
      (107 lesions) with the sheath protected stent delivery system (SDS) and 117
      patients (150 lesions) with the bare stent approach. The number of balloons used
      per lesion in the bare stent group was significantly less than in the SDS group
      (1.9 +/- 0.6 vs. 3.8 +/- 1.2, P < 0.0001). In addition, the procedure time in the
      bare stent group was significantly shorter than in the SDS group (106 +/- 55 vs.
      134 +/- 60 min, P = 0.001). There was no difference in frequency of adverse
      events or stent displacement during the procedure. The bare stenting technique
      decreases the procedure time, reduces the number of balloons used, and is as safe
      as the SDS approach.

PMID- 9554763
TI  - Long-term outcome of intracoronary microstent implantation: lesion matched
      comparison with Palmaz-Schatz stent.
AB  - We performed a lesion matched comparison of AVE Microstent and Palmaz-Schatz
      stent implants with 6 month follow-up angiography to compare the occurrence of
      restenosis. Thirty-three pairs of lesions were matched for lesion location,
      ACC/AHA lesion type, reference diameter, lesion length, and angiographic
      descriptors. Age, sex, clinical profile, and indication for stenting were
      comparable. Quantitative coronary analysis before and after the procedure was
      comparable in the two groups but minimum lumen diameter (MLD) at follow-up was
      less with Microstent--2.01 +/- 1.01 mm than Palmaz-Schatz stent--2.43 +/- 0.96 mm
      (P = 0.05). Binary restenosis was present in 33% and 21% and was diffuse in 55%
      and 29% of the two groups, respectively. Typical angina at follow-up was more
      frequent with Microstent (36%) than Palmaz-Schatz stent (15%; P = 0.038). When
      implanted in lesions of similar complexity, Microstent yields similar post
      procedure angiographic results but smaller MLD at follow-up and more frequent
      angina than Palmaz-Schatz stent.

PMID- 9554764
TI  - Garbage in, garbage out.

PMID- 9554765
TI  - Randomised comparison of Micro Stent I with Palmaz-Schatz stent placement for the
      elective treatment of short coronary stenoses.
AB  - This randomised trial compared the Micro Stent I and the Palmaz-Schatz stent for
      the elective treatment of short (<8 mm long), new-onset coronary stenoses. The
      primary endpoints were restenosis rate and minimal luminal diameter at 6 mo
      angiographic follow-up. The secondary endpoints were angiographic and procedural
      success of stenting and a composite clinical endpoint at 6 mo (death, myocardial
      infarction, and target site revascularisation). A total of 93 patients were
      randomised. Clinical and angiographic characteristics of the two groups were
      comparable. Angiographic success of stenting was 96% in both groups, and there
      were no complications so that the procedural success was also 96% in both groups.
      The restenosis rate was 29% for Micro Stent I and 27% for the Palmaz-Schatz stent
      (P = NS). The minimal luminal diameter at 6 mo was 1.75 +/- 0.72 mm in the Micro
      Stent I group and 1.84 +/- 0.59 in the Palmaz-Schatz group (P = NS). At 6 mo, a
      clinical endpoint was reached by 21% of the patients in the Micro Stent I group
      and by 11% in the Palmaz-Schatz group (P = NS). In conclusion, the elective
      treatment of short coronary stenosis with the Micro Stent I or the Palmaz-Schatz
      stent resulted in similar early and late outcomes. In particular, the late
      angiographic results were very similar.

PMID- 9554766
TI  - Percutaneous transvenous mitral commissurotomy using Inoue balloon in children
      less than 12 years.
AB  - Rheumatic mitral stenosis in some parts of the world afflicts even young
      children. Percutaneous transvenous mitral commissurotomy (PTMC) using Inoue
      balloon in these children is not well reported. Forty-five children (aged 7-12
      years, mean 11.0 +/- 1.2 years) with severe rheumatic mitral stenosis (mitral
      valve area [MVA] 0.64 +/- 0.14 cm2) underwent PTMC. The pulmonary artery wedge
      pressure (PAW) decreased from 24.3 +/- 8.6 to 14.7 +/- 7.2 mmHg (P < 0.0001) and
      mean diastolic gradient decreased from 24.3 +/- 7.7 to 7.9 +/- 5.9 mmHg with the
      final MVA of 1.63 +/- 0.45 cm2 (P < 0.0001). Complications included significant
      mitral regurgitation (MR) in three children and atrial shunting in two patients.
      No procedural death, systemic embolism, and cardiac tamponade were encountered.
      Twenty-four children had maximum balloon size (MBS) same as recommended balloon
      size (RBS) derived according to the height (group I) and 21 children had MBS 1-3
      mm less than RBS (group II). Despite the lesser maximum balloon size, the final
      results were comparable in both groups (MVA group 1.66 +/- 0.44 vs. group II 1.61
      +/- 0.48 P = NS). The incidence of significant MR (2 and 1 in group I and group
      II, respectively) was similar. On follow-up of 20.4 +/- 16.3 months (range 3-56
      months), one child developed restenosis. We conclude that PTMC is safe and
      effective in children less than 12 years of age. However, the smaller balloon
      size than the RBS derived from height may be equally effective and possibly
      safer.

PMID- 9554767
TI  - Percutaneous balloon mitral valvuloplasty with Inoue balloon is applicable to all
      age groups.

PMID- 9554768
TI  - Characterization of the atherosclerotic plaque in the internal mammary artery.
AB  - The current study examines, at both structural and ultrastructural levels,
      representative segments of internal mammary arteries obtained from 15 male
      patients, ranging in age from 45 to 75 years, with signs or symptoms of coronary
      heart disease. These segments were obtained at the time of coronary bypass
      surgery. Of the 15 segments examined, only 2 were found to have atherosclerotic
      plaques. In other segments, only an intimal thickening similar to that observed
      during aging was found. There was evidence of endothelial cell loss and defects
      of internal elastic lamina in the present study; however, there was no evidence
      of lipid accumulation in the intimal region. This observation agrees with
      previous findings that indicate that lipid accumulation is not a necessary factor
      for the formation of atherosclerotic plaques. During the study microfilament
      bundles, the so-called "stress fibers," were also observed in the cytoplasm of
      the luminal side of endothelial cells. Stress fibers are known to be present in
      some endothelial cells in some pathologies such as regeneration after injury or
      hypertension. One of the features of the atherosclerotic plaques from an internal
      mammary artery was the presence of cells with contractile and synthetic
      phenotypes (contractile and synthetic smooth muscle cells), as well as cells with
      intermediate features. Cells with similar characteristics have also been observed
      during the development of the early stages of atherosclerosis, during
      embryological development of vessels, after experimental excimer laser treatment,
      and in primary cell culture. To our knowledge, this is the first report showing
      the ultrastructural features of the atherosclerotic plaques in the internal
      mammary artery.

PMID- 9554769
TI  - Usefulness of collagen plugging with VasoSeal after PTCA as compared to manual
      compression with identical sheath dwell times.
AB  - This study investigated the usefulness of collagen plugging with VasoSeal in
      patients after PTCA compared to a control group having identical sheath dwell
      times and therefore comparable levels of anticoagulation. A total of 150 patients
      were enrolled in this prospective and randomized study. Sheaths were pulled at
      exactly 5 h after arterial puncture. Time to hemostasis and local complications
      were determined. There were no statistical differences in baseline
      characteristics. The mean time to hemostasis in the collagen group was
      significantly shorter (3 +/- 3 min) than that of the control group (17.4 +/- 7
      min). At 24 h, 23% of the collagen group patients had a small, 1% a medium and 4%
      a large hematoma. In the control group, 32% had a small, 4% a medium sized, but
      no patient a large hematoma. After collagen, one patient developed a
      pseudoaneurysm needing vascular surgery. In the control group, no major
      complication occurred. Compared to patients with manual compression at an
      identical sheath dwell time and an identical level of anticoagulation, there was
      a significant reduction in time to hemostasis but no statistical difference
      regarding local complications. Although the incidence of medium or large hematoma
      was low, the trend towards a decreased risk of smaller hematomas seemed to be
      counterbalanced by an increased risk of larger hematomas.

PMID- 9554770
TI  - Arterial sealing: we keep plugging away.

PMID- 9554771
TI  - Transcatheter fenestration of hemi-Fontan baffles after completion of Fontan
      physiology using balloon dilatation and stent placement.
AB  - De novo transcatheter fenestration of hemi-Fontan baffles has not been previously
      described. The purpose of this report is to present our experience in such de
      novo transcatheter fenestration in two consecutive patients with absent
      fenestration in whom the hemi-Fontan baffle was the only direct access to the
      pulmonary venous atrium.

PMID- 9554772
TI  - Stent fenestration of hemi-Fontan baffles: an intriguing addition to the
      armamentarium.

PMID- 9554773
TI  - Coil occlusion of arteriovenous fistula of the vertebral artery in a child.
AB  - A 5-year-old boy with congenital fistula between the right vertebral artery and
      concomitant veins underwent a successful transcatheter fistula occlusion with a
      Gianturco coil.

PMID- 9554774
TI  - Extramural vessel wall hematoma causing a reduced vessel diameter after coronary
      stenting: diagnosis by intravascular ultrasound and treatment by stent
      implantation.
AB  - An extramural vessel wall hematoma occurred immediately after implanting a
      coronary stent in an in-stent-restenosis of the intermedius branch. Angiography
      showed a significant luminal reduction distal to the intervention site.
      Intravascular ultrasound revealed an extramural echolucent zone compressing the
      vessel lumen. Stent implantation compressed the hematoma and allowed adequate
      myocardial perfusion. This demonstrates the value of intravascular ultrasound
      (IVUS) in cases of unusual angiographic results which can help to manage
      complications after coronary intervention.

PMID- 9554775
TI  - Antegrade transseptal coronary angiography: an alternative technique in severe
      vascular disease.
AB  - We report the case of a patient with severe vascular disease in whom retrograde
      access to the aortic root was not possible because of aortoiliac and axillary
      vascular disease. Antegrade coronary angiography was performed through the
      transseptal approach using standard catheters, although several technical
      difficulties were encountered.

PMID- 9554776
TI  - Rotational atherectomy for the treatment of restenotic ostial side branches
      jailed by prior stent placement.
AB  - This report describes the treatment by rotational atherectomy of three restenotic
      ostial diagonal lesions that originated within stented segments of the left
      anterior descending artery. Excellent results were obtained without complications
      to stent architecture.

PMID- 9554777
TI  - Case of tumor neovascularization demonstrated by cardiac catheterization.
AB  - A 46-year-old man presented to his physician with nonspecific abdominal
      complaints. CT of the abdomen was obtained to investigate his symptoms, which
      showed significant pericardial effusion. One week after drainage of the
      pericardial fluid, his symptoms recurred and a transesophageal echo showed a
      right atrial tumor. Cardiac catheterization demonstrated right coronary artery
      neovascularization. A nonresectable primary angiosarcoma was found following
      median sternotomy and biopsy.

PMID- 9554778
TI  - All coronary artery disease is not fatty.

PMID- 9554779
TI  - A rare complication of coronary arteriography.
AB  - We describe a 66-year-old man with acute mesenteric ischemia and myocardial
      ischemia within 6 hr after coronary arteriography. He underwent successful
      emergency surgery with embolectomy of the mesenteric artery and coronary artery
      bypass grafting.

PMID- 9554780
TI  - Coronary embolism following aortic and mitral valve replacement: successful
      management with abciximab and urokinase.
AB  - We report a case of coronary embolism in a 63-year-old woman with St. Jude aortic
      and mitral valve replacements who presented with acute myocardial infarction.
      Urgent catheterization revealed a saddle embolus in the proximal part of the
      circumflex and ramus arteries and another embolus in a diagonal branch. After
      employing angioplasty for the totally occluding diagonal embolus, a combined
      regimen of intracoronary urokinase and intravenous abciximab was successful in
      achieving complete resolution of the emboli.

PMID- 9554781
TI  - Acute coronary artery occlusion likely due to thrombus occurring during coronary
      angiography: report of a case.
AB  - Twenty-five years ago, fatalities due to acute thrombotic coronary occlusion
      occurring during coronary angiography were reported not infrequently, but are
      thought to have been eliminated by changes in technique and equipment. We present
      a case with documentation of a normal coronary arterial tree just before the time
      of an abrupt occlusion, which had the angiographic features of clot. The likely
      source of the thrombus was the arterial sheath. Measures for prevention of this
      complication are discussed.

PMID- 9554782
TI  - Spontaneous migration of a catheter embolus from the left inferior to the right
      inferior pulmonary artery.
AB  - This is the first reported case of a spontaneous migration of an embolized
      catheter fragment from the left side of the pulmonary arterial system to the
      right side.

PMID- 9554783
TI  - Hemodynamic rounds series II: left ventricular puncture for hemodynamic
      evaluation of double prosthetic valve stenosis.

PMID- 9554784
TI  - Prevention of the inadvertent aspiration of air into 6 French guiding catheters
      during Magic Wallstent implantation.

PMID- 9554785
TI  - Coronary artery perforation repair using microcoil embolization.
AB  - An 82-year-old woman undergoing percutaneous transluminal coronary angioplasty
      experienced perforation of the terminal portion of the left anterior descending
      coronary artery caused by guidewire trauma. The coronary artery perforation was
      successfully closed using a vascular occlusion system consisting of individual
      thrombogenic coils delivered to the site. Coronary artery perforation (CAP)
      during percutaneous transluminal coronary angioplasty (PTCA) has been reported to
      occur in less than 1% of cases. The incidence seems to be higher with the new
      interventional devices, e.g., DCA, TEC, and laser CAP may result in pericardial
      hemorrhage and cardiac tamponade or a coronary artery fistula to either the left
      or right ventricle. The management of CAP may include prolonged balloon
      inflations, reversal of anticoagulation, pericardiocentesis, and emergency
      surgery. Proximal perforations sometimes can be managed with vein covered stents.
      We describe another option in the treatment of distal CAP using a vascular
      occlusion system.

PMID- 9554786
TI  - Remote suturing for percutaneous closure of popliteal artery access.
AB  - We present a case of balloon angioplasty of the superficial femoral artery via a
      popliteal artery access with successful percutaneous vascular closure of the
      vascular access site (6-F Techstar). A femoral arterial approach had not been
      feasible due to previous aorto-femoral and femoro-femoral bypass operations.
      Clinical and ultrasound follow-up showed no complications up to 3 months after
      remote suturing.

PMID- 9554787
TI  - Rheolytic thrombectomy of chronic coronary occlusion.
AB  - Percutaneous intervention in patients with intracoronary thrombus continues to
      pose a significant clinical challenge. In this report, we describe the successful
      treatment of a 44-year-old patient with an extensive chronic thrombotic occlusion
      of the right coronary artery using a rheolytic thrombectomy catheter. Despite
      angiographic documentation of coronary thrombosis 104 days prior to treatment and
      a voluminous thrombus burden (60 mm in length x 3 mm in diameter), rapid
      recanalization was accomplished with this device without embolic complications.
      At 1 year clinical follow-up, the patient has remained symptom free. The design
      of this novel device and its mechanism of action are described.

PMID- 9554788
TI  - Stent: the answer!

PMID- 9554789
TI  - Left coronary artery to left ventricular fistula can result in a coronary steal:
      reply to the letter to the editor by Cheng et al.:.

PMID- 9554790
TI  - Management of aortic dissection complicating coronary intervention.

PMID- 9554791
TI  - Closure of patent ductus arteriosus with detachable coils: easy is better than
      hard.

PMID- 9554792
TI  - Protective effects of ethynylestradiol on the hemodynamic changes induced by
      lipopolysaccharide in anesthetized rats.
AB  - Estrogen pretreatment has been reported to protect rats from death induced by
      endotoxin. We investigated the effects of posttreatment with a synthetic
      estrogen, ethynylestradiol, on arterial pressure and hemodynamics in
      thiobutabarbitone-anesthetized rats challenged with Escherichia coli
      lipopolysaccharide. Rats were i.v. injected with lipopolysaccharide (1 mg/kg)
      followed by vehicle or a single dose of ethynylestradiol (0.25, 0.5, or 1 mg/kg)
      1 h later. Another group (time-matched control) was given the vehicle. In the
      time-control group, there was a slight decrease in mean arterial pressure (-10 +/
      3 mm Hg) but no significant changes in cardiac output, total peripheral
      resistance, or heart rate over the 6-h study period. Lipopolysaccharide
      progressively reduced mean arterial pressure and cardiac output (-27 +/- 8 mm Hg
      and -52 +/- 6 ml/min, after 6 h) and increased total peripheral resistance and
      heart rate (+0.33 +/- 0.10 mm Hg/min/ml and +21 +/- 13 beats/min, after 6 h).
      None of the time-control rats died, but 36% of the rats treated with
      lipopolysaccharide died between 3 and 6 h after endotoxin challenge.
      Ethynylestradiol, at 0.25 and 0.5 completely, and at 1 mg/kg partially, restored
      mean arterial pressure and cardiac output at 6 h after injection of
      lipopolysaccharide. Ethynylestradiol at 0.5 and 1 mg/kg, but not 0.25 mg/kg,
      completely reversed the increase in total peripheral resistance at 6 h after
      injection of lipopolysaccharide. Mortality was 14% in each of the three groups of
      rats given ethynylestradiol 1 h after lipopolysaccharide. Therefore posttreatment
      with ethynylestradiol attenuated hemodynamic changes in endotoxic shock.

PMID- 9554793
TI  - Influence of myocardial ischemia and reperfusion on beta-adrenoceptor subtype
      expression.
AB  - The effects of ischemic injury and reperfusion on myocardial beta-adrenoceptor
      expression were examined in dogs after 30 min of left anterior descending
      coronary artery (LAD) ligation. Three sets of six dogs were allocated to either
      sham ligation (group I), 30 min ischemia without reperfusion (group II), or
      ischemia with 1 h of reperfusion (group III). The density of total beta
      adrenoceptors along with beta1- and beta2-adrenoceptor subtypes were compared in
      tissue from the ischemic LAD and nonischemic left lateral zones by using
      radioligand binding with 125-labeled iodocyanopindolol (ICYP). In the control
      animals, there was no difference between total beta-adrenoceptors (43.8 +/- 7.2
      vs. 40.7 +/- 8.0 fmol/mg protein +/- SEM) or percentage beta-adrenoceptor
      subtypes between the two zones. In group II, total beta-adrenoceptors increased
      19.9% (p = 0.03) in the LAD compared with the lateral zone after 30 min of
      ischemia. Both beta-adrenoceptor subtypes increased, but only the increase in
      beta2-adrenoceptor was significant (39.8%; p = 0.02). Animals in group III
      revealed no difference in total beta-adrenoceptors density between LAD and
      lateral zones (48.3 +/- 13.4 vs. 55.2 +/- 8.5 fmol/mg protein). Brief myocardial
      ischemia is associated with an increase in total beta-adrenoceptors, attributed
      predominantly to increased beta2-adrenoceptors density. The increase in beta
      adrenoceptor density is reversible after 1 h of reperfusion.

PMID- 9554794
TI  - UL-FS 49 (zatebradine) does not affect arterial baroreflex in conscious normal or
      aortic-constricted rats.
AB  - Heart-rate reduction is an important element of patient management during cardiac
      bypass surgery and in therapeutic measures for combating ischemia and relieving
      pain in patients with angina. UL-FS 49 is a novel bradycardic agent that
      purportedly acts solely on the sinoatrial node without potentially deleterious
      effects on arterial pressure and cardiac inotropism. However, little is known
      about influences of this agent on neuronal tissue and cardiovascular reflexes.
      Moreover, left ventricular hypertrophy, which often accompanies cardiovascular
      disease, is known to attenuate the arterial baroreflex and could have effects
      interactive with those of UL-FS 49. In this study, the effects of UL-FS 49 on the
      arterial baroreflex were tested in normal rats (N), rats with left ventricular
      hypertrophy 14 days after abdominal aortic constriction (AC), and sham-operated
      controls (SH). Arterial baroreflex sensitivity (BRS) was estimated as the slope
      of the relation between mean arterial pressure (independent variable) and the RR
      interval (dependent variable). At the time of study, the AC group had
      significantly greater mean arterial pressure than either SH or N (159 +/- 2, 122
      +/- 3, and 124 +/- 3 mm Hg, respectively; mean +/- SEM, p < 0.01) and
      significantly greater left ventricular mass to body mass ratio than did SH (3.73
      +/- 0.11, 2.33 +/- 0.11 mg/g; p < 0.01). As expected, BRS was significantly
      depressed in AC, compared with either SH or N (0.52 +/- 0.16, 1.48 +/- 0.12, 1.69
      +/- 0.25 ms/mm Hg, respectively; p < 0.01). Despite its potent dose-dependent
      bradycardic effects in all three groups, UL-FS 49 did not affect BRS
      significantly in any group. These results show that the arterial baroreflex is
      largely unaffected by UL-FS 49 in both normal rats and rats with systemic
      hypertension and left ventricular hypertrophy.

PMID- 9554795
TI  - Reduced responsiveness of [Ca2+]i to adenosine A1- and A2-receptor stimulation in
      the isoproterenol-stimulated ventricular myocytes of spontaneously hypertensive
      rats.
AB  - To determine the modulatory action of adenosine-receptor stimulation on [Ca2+]i
      responses to beta-adrenoceptor stimulation in the heart of the spontaneously
      hypertensive rat (SHR), the electrically induced [Ca2+]i transient in response to
      isoproterenol (ISO) in single ventricular myocytes pretreated with adenosine
      agonists in SHRs and its normotensive control Wistar-Kyoto (WKY) rats was
      measured with a spectrofluorometric method by using fura-2/AM as the calcium
      indicator. In both types of rat, ISO at 0.001-1 microM augmented the electrically
      induced [Ca2+]i transient, and the effect was blocked by a beta-adrenoceptor
      blocker, propranolol. In SHRs that did not exhibit cardiac hypertrophy, the
      resting level of [Ca2+]i and the amplitude of the electrically induced [Ca2+]i
      transient were the same as those in WKY rats, whereas the augmentation of the
      electrically induced [Ca2+]i transient in response to ISO was significantly lower
      than that in WKY rats. In WKY rats, the effects of ISO on the electrically
      induced [Ca2+]i transient were inhibited by the adenosine A1-receptor agonist, R(
      )-N6-(2-phenylisopropyl)adenosine (R-PIA) at 0.01-10 microM. In contrast, the
      effects of ISO were further enhanced by the adenosine A2-receptor agonist, N6-[2
      (3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl)]adenosine (DPMA) at 1-10 microM.
      In SHRs, the inhibitory effect of R-PIA was significantly reduced, whereas the
      excitatory effect of DPMA was absent. The effects of both adenosine-receptor
      agonists in both types of rat were abolished by the respective adenosine-receptor
      antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 3,7-dimethyl-1
      propargylxanthine (DMPX). The results indicate that the modulatory actions of
      adenosine-receptor stimulation on [Ca2+]i response to beta-adrenoceptor
      stimulation in the hearts of SHRs are reduced, which is independent of cardiac
      hypertrophy.

PMID- 9554796
TI  - Stereoisomer-specific inhibition of superoxide anion-induced rat aortic smooth
      muscle cell proliferation by 17beta-estradiol is estrogen receptor dependent.
AB  - An in vitro xanthine/xanthine oxidase reaction system was used to generate
      superoxide anions that significantly stimulated tritiated [3H]thymidine
      incorporation into endothelium-removed (denuded) male rat aortic explants.
      Tritiated thymidine uptake was used as an index of vascular smooth-muscle cell
      (VSMC) proliferation. Superoxide dismutase (SOD) significantly attenuated the
      oxygen free radical-induced proliferative response of these cells. 17Beta
      estradiol (17beta-E) significantly inhibited superoxide anion-induced VSMC
      proliferation. In contrast, the growth-modifying effects of 17beta-E were not
      mimicked by 17alpha-estradiol (17alpha-E), progesterone, or testosterone. The
      pure estrogen receptor (ER) antagonist, ICI 164,384, reversed the growth
      inhibitory effect of 17beta-E. 17Beta-estradiol failed directly to reduce in
      vitro superoxide anion production or to modify xanthine oxidase activity.
      Therefore, these data indicate that 17beta-E, through an ER-dependent mechanism,
      specifically and significantly inhibited superoxide anion-mediated SMC
      proliferation in denuded rat aortic explants.

PMID- 9554797
TI  - Effects of epanolol, a selective beta1-blocker with intrinsic sympathomimetic
      activity, in patients with ischemic left ventricular dysfunction.
AB  - Recently, different beta-blockers have been shown to be effective in the
      treatment of chronic heart failure (CHF), but the importance of their ancillary
      properties is not clear. Epanolol is a selective beta1-blocker with intrinsic
      sympathomimetic activity, which has been shown useful in angina pectoris, but its
      value in patients with left ventricular (LV) dysfunction and CHF is unknown. We
      examined the effects of epanolol in patients with LV dysfunction (n = 8; mean LV
      ejection fraction, 0.33 +/- 0.08) and compared them with patients with normal LV
      function (n = 8; mean LV ejection fraction, 0.52 +/- 0.04). Measurement of
      invasive hemodynamics and neurohormones was performed at rest and during
      myocardial ischemia, which was induced by atrial pacing. All measurements were
      performed before and after epanolol. Before epanolol, pacing-induced ischemia led
      to a similar increase in norepinephrine and coronary sinus blood flow in both
      groups. After epanolol, the increase in neurohormones was more pronounced in the
      group with LV dysfunction (norepinephrine, 1,130 +/- 164 pg/ml for patients with
      LV dysfunction vs. 637 +/- 41 pg/ml for normal subjects; p < 0.05). A similar
      effect was observed for angiotensin II. Further, in the LV-dysfunction group,
      coronary sinus blood flow increased less, and coronary vascular resistance
      decreased less (both values, p < 0.05). Despite the fact that the increase in
      double product was decreased to a similar extent in both groups, ischemia was
      reduced only in normal LV function (p < 0.05). In ischemic LV dysfunction,
      neurohumoral activation after epanolol may impair adequate coronary flow
      response, and this may limit its antiischemic properties. Because of the small
      size of the study, no definitive inference on the clinical benefit of epanolol in
      patients with ischemic LV function can be made from this study.

PMID- 9554799
TI  - Effects of dantrolene sodium on progression of left ventricular hypertrophy
      induced by pressure overload in rats.
AB  - We studied the long-term effects of dantrolene sodium (D), a specific
      sarcoplasmic reticulum (SR) Ca2+-release inhibitor, on the progression of left
      ventricular pressure-overloaded hypertrophy in rats. We treated abdominal aorta
      constricted rats with one of two doses of D for 4 weeks. The extent of
      hypertrophy was expressed as the ratio of left ventricle to body weight.
      Hemodynamic parameters were measured by using a microtip catheter manometer.
      Although a low dose of D (500 mg/L in drinking water) decreased blood pressure to
      normal levels, the progression of cardiac hypertrophy was not inhibited. In
      contrast, a high dose of D (5 mg/kg, i.p.) also reduced blood pressure and
      inhibited the progression of cardiac hypertrophy. Dantrolene sodium had no effect
      on cardiac function in sham-operated rats. Thus control of Ca2+ release from the
      SR might be crucial in regulating the progression of cardiac hypertrophy, the
      final mediator possibly being intracellular Ca2+ concentration.

PMID- 9554798
TI  - Intramural injection of biodegradable microspheres as a local drug-delivery
      system to inhibit neointimal thickening in a rabbit model of balloon angioplasty.
AB  - Restenosis remains the major limitation of coronary angioplasty. The objective of
      this study was to develop microspheres able to be delivered at the angioplasty
      site for long-term drug release and to test their effects in a model of balloon
      angioplasty. Polylactic-co-glycolide acid microspheres (5-10 microm in diameter)
      were prepared by using an oil-in-water emulsion-solvent evaporation method. In
      vitro experiments with hydrocortisone-loaded microspheres revealed a
      hydrocortisone release for 4 weeks. We studied the in vivo effect of injection of
      microspheres into the arterial wall of New Zealand White rabbits by using a
      perforated balloon. Deep penetration of microspheres in the arterial wall was
      documented immediately after angioplasty. Intimal hyperplasia was assessed in
      iliac arteries 4 weeks after angioplasty. The morphometric analysis was performed
      in four groups of animals; the first group was subjected only to conventional
      angioplasty (control, n = 10), whereas the other three groups after conventional
      angioplasty were received perforated balloon angioplasty with saline (n = 10),
      microspheres (n = 10), or hydrocortisone-loaded microspheres (n = 7). Intramural
      injection of saline did not induce greater intimal hyperplasia compared with
      control (0.17 +/- 0.03 vs. 0.18 +/- 0.03 mm2, respectively). Microspheres
      injection was associated with a trend toward a greater degree of intimal
      hyperplasia that did not reach statistical significance. Hydrocortisone-loaded
      microspheres were associated with a significant reduction in intimal hyperplasia
      compared with unloaded microspheres (0.16 +/- 0.02 vs. 0.26 +/- 0.03 mm2,
      respectively). The polylactic-co-glycolide acid microspheres are well tolerated,
      easily injected into the arterial wall, and the increase of intimal hyperplasia
      is easily inhibited by release of hydrocortisone for 4 weeks after initial
      injury.

PMID- 9554800
TI  - Augmented endothelium-dependent contraction to angiotensin II in the SHR aorta:
      role of an inducible cyclooxygenase metabolite.
AB  - The purpose of this study was to investigate the mechanisms involved in the
      angiotensin II-induced increase in the contractile response of the hypertensive
      wall after prolonged incubation in the organ-bath buffer. In 5-h incubated rings,
      the contractile response to angiotensin II in aortic rings with endothelium from
      spontaneously hypertensive rats (SHRs) was markedly exaggerated in comparison to
      2-h incubated rings. No such potentiation was observed in SHR rings after removal
      of the endothelium or in intact and denuded Wistar-Kyoto (WKY) rat rings. Aspirin
      and SQ29548 inhibited and cycloheximide and actinomycin D reduced the time
      dependent enhanced response to angiotensin II in rings with endothelium from
      SHRs. In SHR rings with endothelium incubated for 2 h, the contractions caused by
      angiotensin II were potently inhibited by piroxicam but were unaffected by NS
      398. Conversely, in rings incubated for 5 h, the hyperresponsiveness to
      angiotensin II was inhibited to a greater extent by NS-398 than by piroxicam.
      Piroxicam but not NS-398 had a further inhibitory effect on the residual
      angiotensin II-induced contraction in actinomycin D-treated rings incubated for 5
      h. In conclusion, our study shows that long-term incubation leads to
      hyperresponsiveness to angiotensin II in SHR aorta with endothelium. The enhanced
      response is associated with the induced release of vasoconstrictor prostanoids
      sensitive to the inhibitory effect of NS-398, a preferential inhibitor of COX-2.

PMID- 9554801
TI  - Chronotropic effects of cilostazol, a new antithrombotic agent, in patients with
      bradyarrhythmias.
AB  - Whether phosphodiesterase inhibitors increase the heart rate in patients with
      bradyarrhythmias is not known. We attempted to determine whether the oral
      phosphodiesterase inhibitor cilostazol exhibits beneficial chronotropic effects
      in patients with symptomatic bradyarrhythmias. Twenty patients comprising eight
      with bradycardic atrial fibrillation, eight with sick sinus syndrome, and four
      with Wenckebach-type atrioventricular block, whose 24-h total heart-beat count
      was < or =70,000 beats and whose maximal RR interval was > or =2.5 s, were
      enrolled. Holter recordings (24-h) were made before and 2 weeks after oral daily
      administration of 200 mg of cilostazol. Cilostazol increased the 24-h total heart
      beat count from 77,429 +/- 11,168 to 107,981 +/- 13,536 (95% confidence interval,
      24,605-36,497; p < 0.0001), the minimal heart rate from 33 +/- 9 47 +/- 13
      beats/min (95% confidence interval, 9-19 beats/min; p < 0.0001), and the maximal
      RR interval from 3,149 +/- 1,018 to 2,087 +/- 601 ms (95% confidence interval, 
      1,517 to -608 ms; p = 0.0001). Only two patients had headaches as adverse
      effects. In conclusion, cilostazol had a beneficial positive chronotropic effect
      in patients with bradyarrhythmias, especially with bradycardic atrial
      fibrillation and sick sinus syndrome.

PMID- 9554802
TI  - Antiatherosclerotic and antioxidative effects of captopril in apolipoprotein E
      deficient mice.
AB  - The effect of the angiotensin-converting enzyme (ACE) inhibitor, captopril, on
      the development of atherosclerosis was determined in the apolipoprotein (apo) E
      deficient mice. These mice develop severe hypercholesterolemia and extensive
      atherosclerotic lesions on chow diet, similar to those found in humans.
      Furthermore, in these mice, accelerated atherosclerosis is associated with
      increased plasma lipid peroxidation, a phenomenon that may play a crucial role in
      the buildup of the atherosclerotic lesions. Mice received either placebo or 50
      mg/kg/day of captopril. After 12 weeks of treatment, captopril reduced the aortic
      lesion area by 70% compared with that of the placebo-treated group. Captopril
      also increased the resistance of low-density lipoprotein (LDL) to CuSO4-induced
      oxidative stress, as shown by a significant reduction in the LDL content of
      malondialdehyde (MDA) by 30%, as well as by the prolongation of the lag time
      required for LDL oxidation from 55 min in the placebo-treated mice to 70 min in
      the captopril-treated mice, and reduction of the maximum LDL oxidation at 150 min
      by 35%. In vitro studies demonstrated that preincubation of LDL with captopril,
      inhibited the onset of CuSO4-induced LDL peroxidation up to 120 min, and reduced
      the LDL content of MDA by 90%. We conclude that captopril attenuates
      atherosclerosis in the apo E-deficient mice, and this phenomenon may be related
      to its inhibitory effect on the plasma LDL oxidation.

PMID- 9554803
TI  - SR142948A is a potent antagonist of the cardiovascular effects of neurotensin.
AB  - The novel compound SR142948A was compared with SR48692 as an antagonist of
      neurotensin-induced cardiovascular effects both in vitro and in vivo. SR142948A
      inhibited [125I]-neurotensin binding [median inhibitory concentration (IC50) =
      0.24 +/- 0.01 nM], neurotensin-induced cytosolic free Ca2+ increase (IC50 = 19 +/
      6 nM), and prostacyclin production in human umbilical vein endothelial cells
      (IC50 = 17 +/- 3 nM) at much lower concentrations than did SR48692 (respective
      IC50 values, 14 +/- 5, 41 +/- 16, and 86 +/- 16 nM). Oral administration of
      SR142948A (10 microg/kg) resulted in significant inhibition of neurotensin
      induced blood pressure changes, whereas SR48692 was active only at 10-fold higher
      doses. Furthermore, SR142948A administered i.v. in microg/kg quantities in the
      rat was as active as mg/kg doses of SR48692 on neurotensin-induced increase in
      hematocrit. SR142948A injected intradermally also significantly inhibited
      neurotensin-induced plasma extravasation at concentrations as low as 10
      pmol/site, whereas 1,000 pmol/site of SR48692 were necessary to reach a
      significant inhibition. These data show that SR142948A is a novel, extremely
      potent antagonist of neurotensin-induced cardiovascular responses both in vitro
      and in vivo. SR142948A and SR48692 constitute a pair of nonpeptide neurotensin
      antagonists of different potency, which may be used to probe for the implication
      of neurotensin receptors in physiologic or pathologic phenomena.

PMID- 9554804
TI  - Comparative effects of glibenclamide, tedisamil, dofetilide, E-4031, and BRL
      32872 on protein kinase A-activated chloride current in guinea pig ventricular
      myocytes.
AB  - The modulation of the protein kinase A-activated chloride current (PKA-I[Cl]) may
      lead to modification of the cardiac action potential shape. The purpose of this
      study was to evaluate the effects of glibenclamide, tedisamil, dofetilide, E
      4031, and BRL-32872 on the PKA-I(Cl). Experiments were conducted by using the
      patch-clamp technique in guinea pig ventricular myocytes. PKA-I(Cl) was activated
      by application of 1 microM isoproterenol and was inhibited by 1 microM
      propranolol, 10 microM acetylcholine, or 1 mM 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid (SITS). The sulfonylurea receptor
      inhibitor, glibenclamide, inhibited PKA-I(Cl) at micromolar concentration. Among
      class III antiarrhythmic agents, tedisamil induced a dose-dependent inhibition of
      PKA-I(Cl) with a half effective concentration (EC50) of 7.15 microM (Hill
      coefficient, 0.54). This effect may contribute to action potential widening
      induced by tedisamil. In contrast, the selective inhibitors of the rapid
      component of the delayed rectifier K current (I[Kr]), dofetilide, and E-4031, as
      well as BRL-32872, that blocks I(Kr) and the L-type calcium current, did not
      significantly affect the amplitude of PKA-I(Cl), even at high concentrations (10
      30 microM). These results demonstrate that compounds such as glibenclamide and
      tedisamil that are known to block the adenosine triphosphate (ATP)-sensitive K
      current also affect PKA-I(Cl). Furthermore it appears that blockade of PKA-I(Cl)
      is not a common feature for all class III antiarrhythmic agents.

PMID- 9554805
TI  - Inhibition of sodium current by chloride channel blocker 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in guinea pig cardiac
      ventricular cells.
AB  - The effects of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), a
      potent anion transport blocker, on transmembrane action potentials (APs) and the
      sodium current (I[Na]) of guinea pig ventricular myocytes were examined by using
      conventional microelectrode and whole-cell patch-clamp recording techniques. In
      papillary muscle preparations, DIDS (> or =0.1 mM) suppressed the maximal
      upstroke velocity (.v[max]) of the AP without significant changes in other AP
      parameters. Extracellular application of DIDS on single cardiomyocytes isolated
      from the guinea pig ventricle markedly reduced the peak amplitude of the
      tetrodotoxin (TTX)-sensitive and voltage-activated sodium current. The
      concentration-dependent block of DIDS could be expressed by the Hill equation
      with a Hill coefficient of 0.97 and a dissociation constant of 0.15 mM at a
      holding potential of (VH) -120 mV. DIDS (0.1 mM) shifted the steady-state
      inactivation curve for I(Na) toward more negative potentials by 6.0 +/- 0.5 mV
      and the activation curve to more positive potentials by 5.0 +/- 1.0 mV, although
      the slope factors were unaffected. With repetitive depolarizing pulses from -120
      mV, DIDS produced a use-dependent block on the I(Na). Recovery of I(Na) from
      inactivation was slowed (time constant = 245 ms, compared with 10 ms of control)
      in the presence of 0.1 mM DIDS. In the two-pulse experiments, DIDS produced two
      distinct phases of development of I(Na) block, the rapid phase (tau = 5 ms)
      caused by an open channel block, and the slower phase (tau = 382 ms) induced by
      an inactivated channel block. These results suggest that the Cl- transport
      blocker DIDS has a direct inhibitory effect on the cardiac sodium channel. DIDS
      induced use dependence of I(Na) block may result from the interaction of the drug
      with sodium channels in both the open and inactivated channel states.

PMID- 9554806
TI  - Pharmacologic profile of TA-606, a novel angiotensin II-receptor antagonist in
      the rat.
AB  - This study was carried out to characterize a novel angiotensin II-receptor
      antagonist, TA-606, (3-pentyloxy) carbonyloxymethyl-5-acetyl-2-n-propyl-3-[2'(1H
      tetrazole-5-yl) biphenyl-4-yl]methyl-4,5,6,7-tetrahydro imidazo [4,5-c] pyridine
      4-carboxylate hydrochloride, which is a newly synthesized prodrug of 606A. In
      anesthetized rats, 606A inhibited angiotensin II-induced pressor response with a
      median inhibitory concentration (IC50) of 6 microg/kg, i.v., and was 8 times more
      potent than EXP3174, an active metabolite of losartan. Bioavailability of TA-606
      was 11 times higher than that of 606A in Sprague-Dawley rats, with consistent
      hypotensive potencies in spontaneously hypertensive rats (SHRs). In conscious
      renal hypertensive rats (RHRs) and conscious SHRs, TA-606 lowered the blood
      pressure without any effects on the heart rate, and its effective dose for 30 mm
      Hg (ED30) values were 0.14 and 0.21 mg/kg, p.o., respectively. The effect of TA
      606 lasted > 10 h in both models. Moreover, the effect of TA-606 was
      approximately 30 and 10 times more potent than those of losartan in RHRs and
      SHRs, respectively. TA-606 did not affect the blood pressure in
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats. TA-606 given for 12
      weeks attenuated the development of hypertension in stroke-prone SHRs. These
      results indicate that TA-606 is a potent angiotensin II-receptor antagonist with
      antihypertensive efficacy. Thus TA-606 is suggested to be a possible useful agent
      in the treatment of hypertension.

PMID- 9554807
TI  - Effects of angiotensin II-receptor blockade with losartan on insulin sensitivity,
      lipid profile, and endothelin in normotensive offspring of hypertensive parents.
AB  - Humans genetically predisposed to hypertension tend to develop at a
      prehypertensive stage subtle metabolic and hormonal dysregulations, and certain
      of these could potentially be angiotensin II dependent. Therefore the aim of this
      study was to investigate the effects of the angiotensin II-receptor antagonist
      losartan on insulin sensitivity, lipid profile, and plasma endothelin-1 (ET-1)
      levels in normotensive offspring of hypertensive parents with a randomized,
      double-blind, placebo- controlled, crossover design. Insulin sensitivity index
      (SI), determined by the Minimal Model Method of Bergman, fasting plasma insulin
      and glucose concentrations, serum total and HDL cholesterol, serum triglycerides,
      and plasma ET-1 levels were assessed in 19 young (26.2 +/- 0.7 years, mean +/-
      SEM), healthy, lean [body mass index (BMI), 22.6 +/- 0.7 kg/m2] normotensive male
      offspring of essential hypertensive parents after 14 days of losartan, 50 mg, and
      14 days of placebo, respectively. Compared with placebo, losartan administration
      did not significantly modify SI (12.2 +/- 1.7 vs. 12.7 +/- 1.5 x 10(
      4)/min/microU/ml on placebo), fasting plasma insulin and glucose, as well as the
      areas under the insulin and glucose curves. Plasma ET-1 levels also did not
      differ significantly between the placebo and losartan administration phases (1.1
      +/- 0.06 vs. 1.2 +/- 0.06 pg/ml). However, serum total cholesterol and
      triglycerides decreased significantly with losartan treatment (3.8 +/- 0.2 vs.
      4.1 +/- 0.2 mM and 0.9 +/- 0.1 vs. 1.1 +/- 0.1 mM, respectively; p < 0.01). Body
      weight, BMI, heart rate (HR), blood pressure (BP), and 24-h urinary sodium,
      potassium, and creatinine values were stable throughout the study. These findings
      demonstrate that angiotensin II-receptor blockade with losartan, administered in
      the therapeutic dose of 50 mg daily, does not alter insulin sensitivity
      determined by the Minimal Model Method of Bergman and does not affect ET-1 in
      normotensive offspring of essential hypertensive parents. The normal insulin
      sensitivity in the subjects studied might explain why losartan did not improve
      it. However, losartan significantly reduced serum total cholesterol and total
      triglyceride levels.

PMID- 9554808
TI  - Contribution of bradykinin to the beneficial effects of ramipril in the fructose
      fed rat.
AB  - The contribution of nondegraded bradykinin to the metabolic effects of the
      angiotensin-converting enzyme (ACE)-kininase II inhibitor ramipril was evaluated
      in rats rendered hypertensive, hyperinsulinemic, and hypertriglyceridemic by a
      fructose-enriched diet. The response of blood pressure, insulin, and triglyceride
      levels to concomitant administration of ramipril and the bradykinin antagonist
      HOE 140 was studied. Rats that received ramipril, HOE 140, or not treated at all
      served as controls. Treatment with ramipril reduced levels of both insulin (from
      6.6 +/- 2.0 to 3.6 +/- 1.7 ng/ml; p < 0.05) and triglycerides (from 292 +/- 88 to
      164 +/- 35 mg/dl; p < 0.001) as well as blood pressure (from 144 +/- 6 to 116 +/-
      6 mm Hg; p < 0.001). In contrast, treatment with HOE 140 did not alter any of
      these parameters. The combined treatment, however, blunted the beneficial
      metabolic effects of ramipril on insulin (7.8 +/- 4.4 ng/ml before and 7.7 +/-
      2.9 ng/ml after treatment) and triglycerides (290 +/- 135 mg/dl before and 285 +/
      152 mg/dl after treatment), whereas the hypotensive effect of ramipril was
      preserved (151 +/- 8 mm Hg before and 122 +/- 6 mm Hg after treatment (p <
      0.001). The data suggest that whereas the hypotensive effect is mostly
      angiotensin-II dependent, the advantageous metabolic affect of ramipril is highly
      dependent on the accumulation of bradykinin.

PMID- 9554809
TI  - Diminished responsiveness of Gs-coupled receptors in severely failing human
      hearts: no difference in dilated versus ischemic cardiomyopathy.
AB  - In end-stage heart failure, cardiac beta-adrenoceptors are decreased and cardiac
      Gi protein is increased. We assessed beta-adrenoceptors, G proteins, and effects
      of several beta-adrenoceptor agonists, histamine, and 5-HT on adenylyl cyclase
      activity in right and left atria and left ventricles and on left ventricular
      contractility in six potential heart transplant donors (nonfailing hearts; NFHs)
      and in nine patients with end-stage dilated cardiomyopathy (DCM) and 11 patients
      with end-stage ischemic cardiomyopathy (ICM) to establish whether the functional
      responsiveness of all cardiac Gs-coupled receptors is reduced. Beta-adrenoceptors
      were reduced in all three tissues; in DCM, beta1-adrenoceptors were more markedly
      downregulated; in ICM, both beta1- and beta2-adrenoceptors were diminished. In
      all three tissues, isoprenaline-, terbutaline-, histamine- and 5-HT-induced
      adenylyl cyclase activation was reduced similarly in DCM and ICM. Moreover, in
      DCM and ICM, guanosine triphosphate (GTP)- (involving Gs and Gi) activated
      adenylyl cyclase was significantly diminished, whereas NaF-activated (involving
      only Gs) and Mn2+-activated (acting at the catalytic unit of the enzyme) adenylyl
      cyclase was unaltered. Left ventricular positive inotropic responses to beta1-
      (noradrenaline, dopamine, and dobutamine), beta2- (terbutaline), and beta1- and
      beta2-adrenoceptors (isoprenaline, adrenaline, and epinine), as well as H2
      receptor (histamine) stimulation were significantly reduced. The extent of
      reduction was not different for each agonist in ICM and DCM. We conclude that in
      DCM and ICM, functional responsiveness of all cardiac Gs-coupled receptors is
      similarly reduced.

PMID- 9554810
TI  - Vascular levels and cGMP-increasing effects of nicorandil administered orally to
      rats.
AB  - We examined a relation between cyclic guanosine monophosphate (cGMP) production
      in thoracic aorta, as an indicator probably reflecting the vascular response, and
      the vascular as well as plasma levels of nicorandil administered orally to rats.
      Nicorandil (3 mg/kg) given orally was rapidly absorbed, reaching the maximal
      plasma (approximately 2,600 ng/ml) and vascular concentrations (approximately 176
      ng/g) at 15 min after the dosing and thereafter decreased rapidly. Even 2 h after
      the dosing, the level of the vascular cGMP formation in vivo remained
      significantly higher (approximately 1,000 fmol/mg increase from the control
      level) in the nicorandil-treated group, compared with the vehicle-treated one,
      and was enough to develop pronounced muscle relaxation in in vitro aortic
      preparations. However, it seems that the vascular cGMP increase in vivo was not
      always correlated to the plasma concentration of nicorandil, because the plasma
      concentration (approximately 750 ng/ml corresponding to 3.5 microM) at 2 h after
      the dosing, caused only relatively low cGMP production (300-400 fmol/mg increase
      from the control level), when tested in in vitro aortic preparations. Our study
      may indicate, therefore, that the vascular cGMP elevation in vivo is due to the
      content of nicorandil effectively remaining at its vascular targets of action as
      well as the plasma nicorandil concentration.

PMID- 9554811
TI  - Comparative efficacy of a DA2/alpha2 agonist and a beta-blocker in reducing
      adrenergic drive and cardiac fibrosis in an experimental model of left
      ventricular dysfunction after coronary artery occlusion.
AB  - Attenuation of neuroendocrine activation may be beneficial in congestive heart
      failure. Sympathetic nervous system overactivity can be reduced by receptors
      blockade or by reducing norepinephrine (NE) spillover. This study evaluated and
      compared the effects of a DA2-dopaminergic receptor/alpha2-adrenoceptor agonist
      (CHF-1024) and a beta1-adrenoreceptor antagonist in terms of hemodynamics,
      ventricular remodeling, beta-adrenergic drive, and cardiac fibrosis after
      myocardial infarction (MI) in rats. MI was induced by left coronary artery
      ligation in 213 rats, whereas 12 were left unoperated on. After 2 months, the
      operated-on animals were treated for 1 more month with CHF-1024 at either 0.33
      mg/kg/day (low dose) or 1 mg/kg/day (high dose) or with metoprolol (10
      mg/kg/day), delivered through implanted osmotic minipumps. Plasma concentration
      and urinary excretion of NE were measured before the rats were killed.
      Hemodynamic variables were measured and morphometric analysis was done on the
      diastole-arrested hearts to quantify left ventricular remodeling and interstitial
      collagen density. Metoprolol treatment tended to normalize LV end-diastolic
      pressure (LVEDP). CHF-1024 at either dose, and metoprolol, significantly reduced
      collagen deposition in LV of infarcted animals (from 8.8 +/- 0.5% LV area in
      vehicle-treated rats to 6.6 +/- 0.2% or 6.4 +/- 0.2% after the low or high dose
      of CHF-1024, respectively; p < 0.05). Similarly, CHF-1024 at either dose reduced
      the plasma concentration of NE (from 224 +/- 53 pg/ml to 60 +/- 7 pg/ml or 87 +/-
      13 pg/ml; p < 0.05) and urinary excretion of NE in rats with MI, whereas beta
      blockade did not affect these variables. In conclusion, CHF-1024 infused for 1
      month to rats with LV dysfunction reduced heart rate, NE spillover, and collagen
      deposition, without unwanted effects, only appearing at the higher dose.
      Effective beta-blockade with metoprotol reduced LVEDP with no effects on heart
      function. Neither DA2/alpha2 stimulation nor beta-blockade altered LV remodeling
      after coronary artery ligation.

PMID- 9554812
TI  - KCB-328: a novel class III antiarrhythmic agent with little reverse frequency
      dependence in isolated guinea pig myocardium.
AB  - The effects of 1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxypheneth
      yl)-N-methylamino] ethane hydrochloride (KCB-328), in comparison with those of
      dofetilide, were studied on the action potentials (APs) of isolated guinea pig
      papillary muscles. KCB-328 (0.003-3 microM) concentration-dependently prolonged
      the AP duration at 90% repolarization (APD90) at 1- and 3-Hz pacing, and the
      concentration-response relations at 1 and 3 Hz resemble each other. Dofetilide
      (0.001-1 microM) also produced the concentration-dependent prolongation of APD90
      but more pronouncedly at 1 than at 3 Hz, demonstrating the reverse frequency
      dependent effect. KCB-328 at 0.03, 0.1, 0.3, and 1 microM increased APD90 by 11
      +/- 1, 19 +/- 1, 25 +/- 1, and 29 +/- 1% at 3 Hz and by 9 +/- 1, 19 +/- 2, 27 +/-
      2, and 33 +/- 2% at 1 Hz, respectively. Prolongation of the effective refractory
      period (ERP) by each drug is parallel to those of APD90 at each pacing frequency.
      KCB-328 modified neither the maximal velocity of depolarization, amplitude of AP,
      and resting membrane potential in the fast APs, nor any parameters of the slow
      APs. In a separate experiment, the effects of KCB-328 on the ERP of contractile
      response (ERPc) of excised guinea-pig papillary muscles also were studied at 1
      and 3 Hz. KCB-328 (0.01-10 microM) lengthened the ERPc in a concentration
      dependent and frequency-independent manner as in the electrophysiologic results.
      This frequency-independent ERPc prolongation by KCB-328 was not influenced by
      increased extracellular K+ concentration from 4 to 10 mM. These results suggest
      that KCB-328 might be a selective class III agent with effects that are
      relatively frequency independent.

PMID- 9554813
TI  - Contribution of endothelin to the acute pressor response of L-NAME in stroke
      prone spontaneously hypertensive rats.
AB  - In this study, we examined whether endothelin (ET) plays a role in the short-term
      increase in mean arterial pressure (MAP) after nitric oxide synthase (NOS)
      inhibition with N(omega)-nitro-L-arginine methyl ester (L-NAME) in stroke-prone
      spontaneously hypertensive rats (SHRSPs). Experiments were performed by using
      Inactin-anesthetized male SHRSPs that were pretreated with chlorisondamine to
      block reflex autonomic cardiovascular effects. Injection of L-NAME (10 mg/kg,
      i.v.), but not D-NAME, produced rapid and marked increases (74 +/- 3 mm Hg) in
      MAP that were sustained for >1 h. In SHRSPs that were treated with the ET(A/B)
      receptor antagonist, L-754,142 (15 mg/kg + 15 mg/kg/h), L-NAME increased MAP by
      45 +/- 4 mm Hg (p < 0.0001 compared with L-NAME alone). L-754,142 blocked pressor
      responses to big ET-1 by >90% but was without effect on pressor responses to
      norepinephrine. Plasma levels of ET-1 averaged 5 +/- 1 pg/ml in animals given
      vehicle and were slightly increased in animals given either L-NAME alone (7 +/- 2
      pg/ml) or L-754,142 alone (7 +/- 2 pg/ml) but increased markedly when L-NAME and
      L-754,142 were given together (114 +/- 18 pg/ml). This may relate to an effect of
      L-754,142 to block ET-receptor-mediated clearance of ET-1. We conclude that ET
      plays a role in the short-term pressor response after NOS inhibition in SHRSPs.

PMID- 9554814
TI  - Neutral endopeptidase and angiotensin-converting enzyme inhibitors increase
      nitric oxide production in isolated canine coronary microvessels by a kinin
      dependent mechanism.
AB  - Bradykinin is a substrate for both neutral endopeptidase 24.11 (NEP) and
      angiotensin-converting enzyme (ACE). Our previous studies showed that ACE
      inhibitors can stimulate nitric oxide production in coronary microvessels, which
      is mediated by local kinins. Whether inhibition of NEP also can affect local
      vascular NO production has not been established. To determine the role of NEP in
      the control of NO production, coronary microvessels were isolated from seven
      mongrel dogs. Two NEP inhibitors, phosphoramidon and thiorphan, and an ACE
      inhibitor, ramiprilat, were used. Nitrite, the metabolite of NO in aqueous
      solution, was measured by using the Griess reaction. Phosphoramidon and thiorphan
      (10(-6) M) increased nitrite production from 80 +/- 6 to 136 +/- 6 and 144 +/- 7
      pmol/mg, respectively. Ramiprilat (10(-8) M) increased nitrite production from 78
      +/- 6 to 155 +/- 7 pmol/mg wet weight. The effect of these agents on nitrite
      release was blocked by L-NAME, which inhibits NO synthase, HOE-140, which blocks
      bradykinin B2-receptor, and dichloroisocoumarin, which blocks kinin-forming
      enzymes. These results clearly indicate that inhibition of kinin metabolism by
      using neutral endopeptidase inhibitors increases NO production from coronary
      microvessels. Thus neutral endopeptidase plays an important role in local kinin
      modulated NO production in the coronary microcirculation and NEP inhibitors may
      be useful clinical tools in treatment of cardiovascular disease.

PMID- 9554815
TI  - Effect of chronic blockade of angiotensin II-receptor subtypes on aortic
      compliance in rats with myocardial infarction.
AB  - This study was undertaken to investigate changes in aortic geometry and
      compliance after long-term blockade of angiotensin receptors type 1 (AT1) and AT2
      receptors under basal conditions and after myocardial infarction (MI). Sham
      operated (sham) or MI rats received either no treatment, AT1 antagonist GR138950C
      (GR; 2 mg/kg/day i.v.), or AT2 antagonist PD123319 (PD; 3 mg/kg/day s.c.). After
      3 weeks, mean arterial blood pressure (MAP) was measured. Thoracic aorta
      diastolic diameter (D[dia]), compliance coefficient (CC), and distensibility
      coefficient (DC) were determined noninvasively in anesthetized rats by using
      ultrasound and wall tracking. After the rats were killed, histologic measurements
      were made on aortic cross sections. In sham rats, MAP was reduced by GR treatment
      (76 +/- 6 vs. 106 +/- 5 mm Hg), but not by PD. D(dia) was reduced in both GR
      treated (1.74 +/- 0.08 vs. 2.09 +/- 0.05 mm) and PD-treated (1.83 +/- 0.05 vs.
      2.09 +/- 0.05 mm) sham rats. CC and DC were not modified by either treatment.
      Although media cross-sectional area was not affected by either GR or PD treatment
      in sham rats, media thickness and media/lumen ratio were increased in both cases.
      Induction of MI had no effect on aortic structure, geometry, or mechanics;
      however, treatment with either GR or PD improved DC versus untreated MI rats. We
      conclude that AT1 and AT2 receptors are involved in angiotensin II-mediated
      effects on aortic geometry and mechanics under both basal conditions and after
      MI. Whereas blockade of AT1 receptors most likely influences vascular properties
      through a depressor mechanism, AT2 receptors induce pressure-independent
      remodeling.

PMID- 9554816
TI  - Inhibitory effect of enalapril on neurally mediated syncope in elderly patients.
AB  - A dramatic increase in catecholamine (CA) concentration is believed to be a
      primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The
      hypercontractile state of the heart might be alleviated by angiotensin-converting
      enzyme (ACE) inhibitor through depression of CA release from the sympathetic
      nerve ending. Thus ACE inhibitor might have positive effect on the prevention of
      NMS. In this study, 24 elderly subjects who had reproducible NMS induced with
      head-up tilt test (HUT) were randomized and double-blind divided into placebo and
      ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and
      epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS
      were observed in the two groups. Before administration of enalapril, plasma CA
      concentrations were significantly increased during HUT compared with those in the
      supine position; In contrast, administration of the enalapril (10 mg/day) for >1
      year inhibited the concentration of plasma CA increase and prevented syncope in
      all 12 patients (p < 0.05); however, placebo had no effect on plasma CA
      concentrations and syncope disappeared in only two of 12 patients after
      administration of placebo. From this study, we conclude that enalapril can
      prevent NMS in patients, presumably because of its part in the inhibition of CA
      release from sympathetic nerve endings.

PMID- 9554817
TI  - Influence of the renal endothelin A system on the autoregulation of renal
      hemodynamics in SHRs and WKY rats.
AB  - In this study, we investigated the influence of a short-term blockade of the
      renal endothelin A system on the autoregulation of total renal blood flow,
      cortical renal blood flow, and pressure-dependent plasma renin activity in
      spontaneously hypertensive rats (SHRs) and normotensive controls [Wistar-Kyoto
      (WKY) rats]. In anesthetized rats, renal blood flow was measured by a transit
      time flow probe and cortical blood flow by a laser flow probe. Blood samples were
      taken for measurement of plasma renin activity. Renal perfusion pressure was
      reduced in 5-mm Hg steps by means of a servocontrolled electropneumatic device by
      an inflatable suprarenal cuff. During the experiments, the rats (n = 6, each
      group) received an intrarenal infusion of either the selective endothelin A
      receptor antagonist BQ123 (3 mg/kg/h) or vehicle. We observed an improvement of
      total and cortical blood flow autoregulation as indicated by a shift of lower
      limits of autoregulation to lower threshold pressures [103 +/- 2 vs. 132 +/- 4 mm
      Hg compared with 98 +/- 3 vs. 120 +/- 4 mm Hg (mean +/- SEM); p < 0.01 resp. p <
      0.05] in BQ123-treated SHRs, whereas BQ123 had no influence on breakpoints of
      autoregulation in WKY rats (p > 0.05). Pressure-dependent plasma renin activity
      in SHRs was not influenced by BQ123. Renal blood flow autoregulation is improved
      in SHRs after short-term blockade of the renal endothelin A system. This effect
      is independent of the renin-angiotensin system. The endothelin A system does not
      seem to play an important role in the autoregulation of renal blood flow in
      normotensive WKY rats.

PMID- 9554818
TI  - Intraoperative blood salvage (IOBS) for tumor surgery.

PMID- 9554819
TI  - Cytokine production and nutritional status in hemodialysis patients.
AB  - Malnutrition is an important predictor of mortality in patients on chronic
      hemodialysis, however the pathogenesis of wasting in this population remains
      unclear. Experimental data suggest that the dialysis procedure per se leads to
      enhanced catabolism, as well as direct loss of plasma amino acids and proteins
      into the dialysate. In the present study, the primary hypothesis examined is that
      hemodialysis-induced cytokine production is associated with reductions in lean
      body mass and other plasma markers of nutrition. We used the production of
      interleukin-1 receptor antagonist (IL-1Ra) by peripheral blood mononuclear cells
      (PBMC) as an indicator of cytokine production. PBMC were obtained pre-dialysis on
      the first and second sessions of the week in a cohort of 16 patients on chronic
      hemodialysis using reprocessed cellulose dialyzers who fulfilled rigorous entry
      criteria designed to eliminate known etiologies of increased cytokine production,
      e.g. chronic infections. PBMCs were either immediately frozen (cell content) or
      incubated for 24 hours at 37 degrees C in the presence or absence of endotoxin 10
      ng/ml and total IL-1Ra was measured by radioimmunoassay. Nutritional staus was
      assessed using body mass index (BMI), total body potassium (TBK), anthropometry
      derived arm muscle area (AMA), and measurements of plasma albumin, transferrin,
      total cholesterol, and triglycerides. Over the subsequent 3 months, patients were
      monitored carefully for pyrogen reactions, hemodynamic stability and intra
      interdialytic symptoms. There was a direct correlation of cell content of IL-1Ra
      with several indices of nutritional status including BMI (r = 0.90, p = 0.0001),
      AMA (r = 0. 77, p = 0.0008), serum total cholesterol (r = 0.57, p = 0.03) and
      serum triglycerides (r = 0. 73, p = 0.002). Endotoxin-stimulated IL-1Ra
      production correlated directly with AMA (r = 0.59, p = 0.02), TBK (r = 0.71, p =
      0.01) and serum triglycerides (r = 0.51, p = 0.05). These studies suggest a
      direct correlation between nutrition and cytokine production, and that
      malnutrition could depress cytokine production and potentially contribute to
      reduced immune responsiveness in patients on chronic hemodialysis.

PMID- 9554820
TI  - Efficacy and tolerability of recombinant human erythropoietin treatment in pre
      dialysis patients: results of a multicenter study.
AB  - Chronic renal failure is characterized by a normochromic normocytic anemia, the
      severity of which generally increases during progression toward uremia. The
      purpose of the study was to evaluate the efficacy and safety of recombinant human
      erythropoietin (rHu-EPO) given subcutaneously (s.c.), the dose required to reach
      and maintain Hb levels within 10 and 11 g% and its effects, if any, on the
      progression of chronic renal failure. Eighty-four pre-dialysis patients (46 F,
      38M, age 61.7+/-13.9 years) with Hb levels between 6 and 9 g% and serum
      creatinine ranging from 3 to 9 mg/dl were treated with s.c. rHu-EPO (2000 U/twice
      weekly). After 6 weeks, if Hb increase was below 1 g%, 1000 U of s.c. rHu-EPO
      were added at each administration (3000 U twice weekly). Once the Hb target was
      reached (10-11 g%), the rHu-EPO weekly dose was halved and administration reduced
      to once weekly. The patients showed a significant rise in mean Hb values
      (p<0.001) after 3 months. Mean Hb values were as follows: 8.00+/-0.77 g%
      (pretreatment), 9.35+/-1.0 (3rd month), 10.06+/-1.04 (6th month), 10.25+/-0.62 g%
      (12th month). The mean rHu-EPO doses were 4000 U/w (start of the study), 3592+/
      1685 U/w (6th month), 2840-/+1178 U/w (12th month). Renal function was evaluated
      by plotting the reciprocal of serum creatinine values vs time with a two period
      comparison: period A (retrospective-8 mo); period B (prospective-12 mo). The
      residual renal function was not impaired by rHu-EPO therapy. Meanwhile, no
      relevant modifications were observed in mean blood pressure values. Low doses of
      s.c. rHu-EPO were well tolerated, safe and effective; this therapeutic approach
      should therefore be considered for the improvement of anemia in pre-dialysis
      patients. A slow and gradual correction of anemia induces an improved sense of
      well being and a more active of life style.

PMID- 9554821
TI  - Phosphate-binding capacities of calcium and aluminum formulations.
AB  - Calcium and aluminum phosphate binders are used to treat hyperphosphatemia which
      is responsible for the development of osteodystrophy commonly seen in patients
      with end-stage renal disease. The purpose of this study was to determine the
      phosphate binding capacities of several frequently used calcium and aluminum
      formulations. The effect of formulation types on phosphate binding was evaluated.
      Calcium and aluminum phosphate binders were administered to six healthy
      volunteers after phosphate load on separate study days. Total urine outflow was
      collected afterwards to determine the amount of phosphate recovered, which
      indicates the ability of the phosphate binder to reduce gastrointestinal
      phosphate absorption. The amounts of urinary phosphate recovered were different
      after administration of the phosphate binders. Calcium acetate resulted in the
      least amount of phosphate excreted. Calcium carbonate suspension, when compared
      with the tablet formulation, caused a smaller amount of phosphate excreted in the
      urine. Different phosphate binders formulations were found to have different
      phosphate binding capacities. Patients should therefore be closely monitored for
      efficacy after switching from one phosphate binder to another.

PMID- 9554822
TI  - Fatal hepatic failure caused by miliary tuberculosis in a hemodialysis patient:
      case report.
AB  - A 57 year-old male dialysis patient died soon after the onset of high fever,
      hypoglycemia, and disturbance of consciousness. Autopsy revealed granulomatous
      lesions associated with caseous necrosis mainly found in the liver, despite the
      absence of pulmonary changes on chest radiographs performed during the patients
      illness. It appears that tubercle bacilli were hematogenously disseminated mainly
      to the liver causing miliary tuberculosis without producing typical diffuse
      lesions in the lungs. Since tuberculosis is a common complication in hemodialysis
      patients, the potential development of atypical miliary tuberculosis should
      always be borne in mind.

PMID- 9554823
TI  - A computer controlled mock circulatory system for mono- and biventricular assist
      device testing.
AB  - The clinical use of heart assist devices for heart recovery, implies the problem
      of their in vitro testing and training to use. In a mock circulatory system
      developed to this aim, the main problem is reproducing interaction among the
      device, the ventricle and the circulatory network. This can be analysed by the
      position, on the p-v plane, of the working point defined by the intersection
      between end systolic ventricular (ESPVR) and arterial elastance lines. The system
      developed on this basis, connectable to mono- and biventricular parallel assist
      devices, was a closed loop model including systemic and pulmonary circulation.
      The arterial trees were reproduced by two windkessels with adjustable peripheral
      resistance, and the Starling's law of the heart by a variable elastance model.
      The software controls and monitors circulatory parameters and variables. Results
      showed the behavior of the system with preload or afterload changes. Further, the
      reproduction of physiological, pathological (obtained by modifying slope and
      volume intercept of the ESPVR line) and LVAD assisted circulatory conditions was
      shown. The assistance effect was underlined by the changes in the ventricular
      work cycle and in hemodynamics variables. The evaluation of the effect of device
      control strategy on the ventricle and its energetics (on p-v plane) were among
      the main characteristics of this system, which ought to be further improved to
      test devices such as the IABP, which requires a different aortic model.

PMID- 9554824
TI  - Test procedure for artificial mitral valves.
AB  - The flow curve of a valve-tester has a great influence on the performance of a
      valve. Usually the flow curve of the aorta is used. However, the mitral valve
      flow curve differs greatly from the flow curve of the aortic valve. It varies
      with the pulse rate and is further changed in patients with certain heart
      diseases. To investigate the different mitral flow conditions, ultrasonic flow
      curves from patients with a mechanical artificial mitral valve were analyzed. The
      curves show that a mitral valve prosthesis has not only to work under
      physiological flow conditions, but also in pathologically deviant flows.
      According to these results three different characteristic flow curves were
      selected and used to test several valves with a computer controlled valve-tester.
      The mean diastolic pressure difference and the whole closing behavior were
      influenced by the flow curve; and the differences in energy losses were
      particularly great. This indicates, that the flow curve must be adjusted
      appropriately.

PMID- 9554825
TI  - Positive biochemical effects of a bioartificial liver support system (BALSS) in a
      porcine fulminant hepatic failure (FHF) model.
AB  - This study describes biochemical changes in the plasma and blood of pigs with
      devascularised livers treated in a bioartificial liver support system (BALSS).
      Porcine hepatic cells were incubated with collagen-coated dextran microspheres
      (CDM) for 3 hours and the medium tested to determine cellular metabolic activity.
      Incubation continued for a further 18 hours during which the hepatic cells attach
      to the CDM. The CDM-attached cells were inoculated into a hollow fibre bioreactor
      which was part of an extracorporeal support system. Hepatic cell content of the
      bioreactor was 6 x 10(9) cells. The system was tested in a controlled trial in
      pigs prepared in a surgical model of fulminant hepatic failure (FHF). When plasma
      from FHF pigs was circulated through the device containing hepatic cells, there
      was significantly less increase in the accumulation of ammonia and most amino
      acids, together with a decrease in plasma lactate and of one amino acid, compared
      to control experiments when hepatic cells were excluded. We conclude that primary
      porcine hepatocytes can contribute beneficial metabolic function in a BALSS.

PMID- 9554826
TI  - Gait restoration in a spinal cord injured subject via neuromuscular electrical
      stimulation controlled by an artificial neural network.
AB  - Attempts to restore gait in spinal cord injured subjects have stumbled on control
      difficulties associated to the neuromuscular system's non-linearity and time
      variance. Thus, a simple autoadaptive artificial neural network has been devised
      to control gait swing generation by means of neuromuscular electrical
      stimulation. Both theoretical and experimental approaches were taken. The
      computer-based system consisted of a three-layer artificial neural network that
      read angular data from the hip, knee and ankle joints. The output signal
      consisted of variations on the applied stimulation pulse width. Surface
      electrical stimulation was applied to the femoral and peroneal nerves of one leg.
      Neural network training included off-line supervised learning schemes. The system
      was tested on a male subject with an incomplete C6-level lesion. Several tests
      were run to determine whether the off-line trained neural network could correctly
      control the motion. The effect of on-line learning upon the control performance
      was also evaluated. The system was found to control the motion with success only
      at times. Control performance was found to improve in response to the application
      of on-line learning. Learning stability following on-line learning was found to
      be satisfactory. In a final test, the artificial neural system had appropriate
      responses to an initial perturbation, which suggests that further research in
      this area should be pursued.

PMID- 9554827
TI  - Granulocyte transfusion in leukopenic children by simplified leukapheresis of
      related donors.

PMID- 9554828
TI  - Phagomimetic action of antimicrobial agents.
AB  - A wide variety of extracted and synthesised drug molecules have electron transfer
      capabilities which allow them to generate reactive oxygen species (ROS). In
      particular, many antibiotics that kill or inhibit bacteria, yeasts and cancer
      cells readily transfer electrons to oxygen making superoxide and hydrogen
      peroxide in the process. When suitable redox active forms of iron are available,
      Fenton chemistry occurs generating the highly damaging hydroxyl radical. This
      type of chemistry is very similar to that which evolved within phagocytic cells
      as part of their microbial killing armoury. Many antibiotics, when used in model
      systems, have well defined pharmacological actions against key cellular
      functions, but their clinical usefulness is also often demonstrable at
      concentrations in vivo well below their in vitro minimum inhibitory
      concentrations. These observations have led us to propose that a common mechanism
      exists whereby phagocytic cells and antibiotics exploit the use of ROS for
      microbial killing.

PMID- 9554829
TI  - Plasma levels of antioxidant vitamins, selenium, total sulfhydryl groups and
      oxidative products in ischemic-stroke patients as compared to matched controls in
      Taiwan.
AB  - The possible involvement of oxidative damage and antioxidant protection has been
      suggested in the pathogenesis of stroke which is the second-leading cause of
      death in Taiwan. In this study we investigated the relationship between ischemic
      stroke and plasma status of antioxidants and oxidative products. Plasma levels of
      vitamin A, alpha-tocopherol, carotenoids, selenium (Se), total SH groups (T-SH),
      thiobarbituric acid-reactive substances (TBARS) and protein carbonyl, a marker of
      protein damage, were determined in ischemic-stroke patients (n = 36, blood
      sampled within 24 hrs after the clinical event) in comparison with 21 matched
      controls. The cholesterol-adjusted carotenoids and vitamin E were significantly
      lower (P < 0.05) in the plasma of ischemic-stroke patients than those of the
      controls. TBARS were higher (P < 0.05) in the patients than in the controls but
      Se, T-SH and protein carbonyls were not significantly different between the two
      groups. Separation of the patients into small-artery ischemic stroke (SAIS, n =
      17) and large-artery ischemic stroke (LAIS, n = 19) groups revealed that both
      carotenoids/cholesterol and vitamin E/cholesterol ratios were significantly lower
      in both LAIS and SAIS groups than the controls (n = 21) while vitamin
      A/cholesterol was not different among the three groups. TBARS were only
      significantly higher in the LAIS group. The results demonstrated that, within 24
      hrs after the clinical event, the acute-ischemic stroke patients had lowered
      levels of cholesterol-adjusted carotenoids and alpha-tocopherol but elevated
      levels of TBARS in the plasma as compared to the matched controls. It remains to
      be resolved as to whether enhanced lipid peroxidation is a cause or a result of
      lowered antioxidants in ischemic stroke.

PMID- 9554830
TI  - Lipid peroxidation, tissue necrosis, and metabolic and mechanical recovery of
      isolated reperfused rat heart as a function of increasing ischemia.
AB  - Isolated Langendorff-perfused rat hearts, after 30 min of preperfusion, were
      submitted to increasing times of global normothermic ischemia (1, 2, 5, 10, 20
      and 30 min) or to the same times of ischemia followed by 30 min of reperfusion.
      Analysis of malondialdehyde, ascorbic acid, oxypurines, nucleosides, nicotinic
      coenzymes and high-energy phosphates was carried out by HPLC on neutralized
      perchloric acid extracts of freeze-clamped tissues. In addition, maximum rate of
      intraventricular pressure development and cardiac output of malondialdehyde,
      lactate dehydrogenase, oxypurines and nucleosides were monitored during both
      preperfusion and reperfusion. Besides decreasing energy metabolites and nicotinic
      coenzyme pool, prolonged ischemia produced oxidation of significant amounts of
      hypoxanthine and xanthine to uric acid and generation of detectable levels of
      malondialdehyde (0.002 micromol/g dry weight). After oxygen and substrate
      readmission, tissue and perfusate malondialdehyde increased only if previous
      ischemia was longer than 5 min, while lactate dehydrogenase was detected in
      perfusate of reperfused hearts following 10, 20, and 30 min of ischemia. Highest
      values of tissue malondialdehyde and total malondialdehyde output were recorded
      in reperfused hearts subjected to 30 min of ischemia (0.043 micromol/g dry weight
      and 0.069 micromol/30 min/g dry weight, respectively). Since tissue
      malondialdehyde was observed without detectable lactate dehydrogenase release in
      perfusate, it might be stated that malondialdehyde generation (i.e., lipid
      peroxidation) temporally preceded lactate dehydrogenase release (i.e., tissue
      necrosis). In reperfused hearts, evaluation of myocardial energy state and of
      mechanical recovery allowed us to determine times of ischemia beyond which
      reperfusion did not positively affect these metabolic and functional parameters.
      Main findings are that, under these experimental conditions, lipid peroxidation
      might be the cause and not the consequence of tissue necrosis and that duration
      of ischemia might be the factor deciding effectiveness of reperfusion.

PMID- 9554831
TI  - Serum of Behcet's disease enhances superoxide production of normal neutrophils.
AB  - Using an MCLA-dependent chemiluminescence technique, we evaluated superoxide
      production by neutrophils isolated from 7 patients with Behcet's disease. After
      stimulation by phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine
      or opsonized zymosan, neutrophils from the patients produced significantly more
      superoxide than those from 20 controls. Pretreatment of control neutrophils with
      serum prominently enhanced superoxide production, and serum from Behcet's disease
      patients had a significantly greater effect than that from controls. These
      findings suggest that serum from patients with Behcet disease contains the
      priming factor(s) that can enhance enhanced superoxide production by neutrophils
      in response to stimulation.

PMID- 9554832
TI  - Generation of oxygen radicals from iron complex of orellanine, a mushroom
      nephrotoxin; preliminary ESR and spin-trapping studies.
AB  - Orellanine, [2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide, is the toxin
      responsible for the lethal nephrotoxicity of some Cortinarius mushrooms. Our
      present ESR and spin-trapping studies of the redox properties of the system of
      non-illuminated orellanine, ferrous iron and dioxygen contribute to understanding
      the molecular mechanism of its toxicity. UV-visible spectrophotometry, cyclic
      voltammetry and ESR in frozen medium showed the formation of a wine-red tris
      complex, Fe(III)Or3. This ferric complex is easily reducible (Ep = -565 mV vs
      Ag/AgCl/3M KCl at pH 7), involving a one-electron reversible process. Spin
      trapping using DMPO is employed to detect the generation of superoxide anion and
      hydroxyl radicals. The instantaneous one-electron oxidation of ferrous ions in
      the presence of the toxin under air is concomitant with dioxygen consumption as
      supported by dioxygen consumption. GSH involves the toxin and ferrous ions under
      air in a redox cycling process resulting in the production of glutathionyl and
      oxygen free radicals, observed for the first time with an iron complex of a
      mushroom toxin. In most cases, EDTA is not able to prevent the Fe(III)Or3 and
      radical formation. The ortho-dihydroxylated groups borne by the di-N-oxidized
      bipyridine structure and not the bipyridine structure itself, are responsible for
      the formation of a stable ferric complex at pH 7, as they are for the generation
      of an apparently stable ortho-semiquinone anion radical. These one-electron
      mechanisms may play a major role in some of the known toxic effects of
      orellanine.

PMID- 9554833
TI  - Nasal cavity lining fluid ascorbic acid concentration increases in healthy human
      volunteers following short term exposure to diesel exhaust.
AB  - To determine if diesel exhaust (DE) exposure modifies the antioxidant defense
      network within the respiratory tract lining fluids, a randomized, single blinded,
      crossover control study using nasal lavage and flexible video bronchoscopy with
      bronchial and bronchoalveolar lavage was performed. Fifteen healthy, non-smoking,
      asymptomatic subjects were exposed to filtered air or diluted diesel exhaust
      (300mg m(-3) particulates, 1.6ppm nitrogen dioxide) for one hour on 2 separate
      occasions, at least three weeks apart. To examine the kinetics of any DE-induced
      antioxidant reactions, nasal lavage fluid and blood samples were collected prior
      to, immediately after, and 5 1/2 hours post exposure. Bronchoscopy was performed
      6 hours after the end of DE exposure. Ascorbic acid, uric acid and reduced
      glutathione (GSH) concentrations were determined in nasal, bronchial,
      bronchoalveolar lavage and plasma samples. Malondialdehyde (MDA) and protein
      carbonyl concentrations were determined in plasma and bronchoalveolar lavage
      samples. Nasal lavage ascorbic acid concentration increased 10-fold during DE
      exposure [1.02 (0.26-2.09) Vs 7.13 (4.66-10.79) micromol/L(-1)], but returned to
      basal levels 5.5 hours post-exposure [0.75 (0.26-1.51) micromol/L(-1)]. There was
      no significant effect of DE exposure on nasal lavage uric acid or GSH
      concentration. DE exposure did not influence plasma, bronchial wash, or
      bronchoalveolar lavage antioxidant concentrations and no change in MDA or protein
      carbonyl concentrations were found. The physiological response to acute DE
      exposure is an increase in the level of ascorbic acid in the nasal cavity. This
      response appears to be sufficient to prevent further oxidant stress in the
      respiratory tract of normal individuals.

PMID- 9554834
TI  - Re-appraisal of the tocopheroxyl radical reaction with beta-carotene: evidence
      for oxidation of vitamin E by the beta-carotene radical cation.
AB  - Photobleached beta-carotene (Car) is regenerated in hexane on a microsecond
      timescale in the presence of alpha-tocopherol (TOH) but not when alpha-tocopherol
      is absent, as studied by laser flash photolysis. Beta-carotene radical cations
      (Car.+) likewise react with (excess) alpha-tocopherol: Car.+ + TOH-->Car + TO. +
      H+ (second-order rate constant of k = 1.7 +/- 0.1 x 10(7) M(-1) s(-1) in
      homogeneous di-tert-butylperoxide/benzene at 20 degrees C) rather than alpha
      tocopheroxyl radicals (TO.) reacting with beta-carotene. In hexane, hexane
      radicals formed by pulse radiolysis react considerably faster with beta-carotene
      (k = 2.1 +/- 0.1 x 10(9) M(-1) s(-1)) than with alpha-tocopherol (k = 4.9 +/- 0.1
      x 10(6) M(-1) s(-1)). No evidence was obtained for a slower rate of beta-carotene
      radical cation formation in beta-carotene/alpha-tocopherol mixtures resulting
      from alpha-tocopheroxyl radical oxidation of beta-carotene. Steady-state
      radiolysis experiments confirmed that alpha-tocopherol protects beta-carotene
      from oxidation by hexane radicals. In both solvent systems, beta-carotene is
      regenerated from the radical cation by alpha-tocopherol rather than alpha
      tocopherol being regenerated by beta-carotene from the alpha-tocopheroxyl
      radical.

PMID- 9554835
TI  - Antioxidant vitamin levels in plasma and low density lipoprotein of obese girls.
AB  - To investigate the antioxidant status of obese children, we analyzed beta
      carotene and alpha-tocopherol levels in plasma and low density lipoprotein (LDL).
      We also analyzed the fatty acid composition of LDL as a substrate for oxidative
      stress. The plasma beta-carotene and alpha-tocopherol levels were relatively
      lower in obese girls than in normal controls. However, the plasma alpha
      tocopherol/lipids ratio was significantly lower in obese girls than in normal
      controls. Both LDL beta-carotene and LDL alpha-tocopherol levels were
      significantly lower in obese girls than in normal controls, although no obvious
      differences were observed in plasma levels. In obese girls LDL contained more
      polyunsaturated fatty acid (PUFA) compared with normal controls. When the
      peroxidizability index (PI) was calculated to estimate the susceptibility of
      lipids to oxidative stress, obese girls had significantly higher PI values than
      normal controls. Both the LDL beta-carotene/PI ratio and the LDL alpha
      tocopherol/PI ratio were significantly lower in obese girls than in normal
      controls. These results indicate the increased susceptibility of LDL to oxidative
      stress in obese girls which may promote atherosclerosis later in life.

PMID- 9554836
TI  - Effect of alpha-tocopherol status on alpha-tocopherol transfer protein expression
      and its messenger RNA level in rat liver.
AB  - Studies were designed to explore the role of vitamin E nutritional status in
      regulating the synthesis of alpha-tocopherol transfer protein (alphaTTP) in rat
      liver. In vitamin E-replete rats, expression of this protein and its specific
      messenger RNA (mRNA) was decreased by about 300% compared with rats with normal
      vitamin E levels. In vitamin E-depleted rats, the alphaTTP-specific mRNA level
      increased to about 150% of that in the normal vitamin E group. However, protein
      expression remained constant. These findings indicate that the synthesis of
      alphaTTP can be regulated by the vitamin E nutritional status.

PMID- 9554837
TI  - In vivo dual effects of vitamin C on paraquat-induced lung damage: dependence on
      released metals from the damaged tissue.
AB  - Vitamin C, a potent antioxidant, can act as a pro-oxidant in the presence of free
      transition metal ions by accelerating the Fenton reaction. An in vivo pro-oxidant
      role of vitamin C has been suggested, but direct evidence for it is scant. Here,
      we report the dual role of vitamin C on paraquat-induced lung injury, which
      appears to depend on the metal ions released from damaged cells. Vitamin C (10
      mg/kg) given at the time when the extensive tissue damage was in progress
      aggravated the oxidative damage, while it protected against the damage when given
      before the initiation of the damage. The extent of oxidative tissue damage was
      monitored by measuring the expiratory ethane, one of the hydrocarbons produced
      during lipid peroxidation. Deferoxamine, given intraperitoneally as a bolus dose
      of 50 mg/kg, completely blocked the aggravation of oxidative damage by vitamin C.
      Moreover, deferoxamine unmasked the antioxidant effect of vitamin C. The results
      show that vitamin C can either aggravate or alleviate the oxidative tissue damage
      depending on the presence of metal ions released from damaged cells.

PMID- 9554838
TI  - Structure and function in the nucleus.
AB  - Current evidence suggests that the nucleus has a distinct substructure, albeit
      one that is dynamic rather than a rigid framework. Viral infection, oncogene
      expression, and inherited human disorders can each cause profound and specific
      changes in nuclear organization. This review summarizes recent progress in
      understanding nuclear organization, highlighting in particular the dynamic
      aspects of nuclear structure.

PMID- 9554839
TI  - Intense sub-kilometer-scale boundary layer rolls observed in hurricane fran 
AB  - High-resolution observations obtained with the Doppler On Wheels (DOW) mobile
      weather radar near the point of landfall of hurricane Fran (1996) revealed the
      existence of intense, sub-kilometer-scale, boundary layer rolls that strongly
      modulated the near-surface wind speed. It is proposed that these structures are
      one cause of geographically varying surface damage patterns that have been
      observed after some landfalling hurricanes and that they cause much of the
      observed gustiness, bringing high-velocity air from aloft to the lowest
      observable levels. High-resolution DOW radar observations are contrasted with
      lower-resolution observations obtained with an operational weather radar, which
      underestimated peak low-level wind speeds.

PMID- 9554840
TI  - Switching supramolecular polymeric materials with multiple length scales 
AB  - It was demonstrated that polymeric supramolecular nanostructures with several
      length scales allow straightforward tailoring of hierarchical order-disorder and
      order-order transitions and the concurrent switching of functional properties.
      Poly(4-vinyl pyridine) (P4VP) was stoichiometrically protonated with methane
      sulfonic acid (MSA) to form P4VP(MSA)1.0, which was then hydrogen-bonded to
      pentadecylphenol. Microphase separation, re-entrant closed-loop macrophase
      separation, and high-temperature macrophase separation were observed. When MSA
      and pentadecylphenol were complexed to the P4VP block of a microphase-separated
      diblock copolymer poly[styrene-block-(4-vinyl pyridine)], self-organized
      structures-in-structures were obtained whose hierarchical phase transitions can
      be controlled systematically. This microstructural control on two different
      length scales (in the present case, at 48 and 350 angstroms) was then used to
      introduce temperature-dependent transitions in electrical conductivity.

PMID- 9554841
TI  - Platinum catalysts for the high-yield oxidation of methane to a methanol
      derivative 
AB  - Platinum catalysts are reported for the direct, low-temperature, oxidative
      conversion of methane to a methanol derivative at greater than 70 percent one
      pass yield based on methane. The catalysts are platinum complexes derived from
      the bidiazine ligand family that are stable, active, and selective for the
      oxidation of a carbon-hydrogen bond of methane to produce methyl esters.
      Mechanistic studies show that platinum(II) is the most active oxidation state of
      platinum for reaction with methane, and are consistent with reaction proceeding
      through carbon-hydrogen bond activation of methane to generate a platinum-methyl
      intermediate that is oxidized to generate the methyl ester product.

PMID- 9554842
TI  - The Lost Colony and Jamestown droughts.
AB  - Tree-ring data from Virginia indicate that the Lost Colony of Roanoke Island
      disappeared during the most extreme drought in 800 years (1587-1589) and that the
      alarming mortality and the near abandonment of Jamestown Colony occurred during
      the driest 7-year episode in 770 years (1606-1612). These extraordinary droughts
      can now be implicated in the fate of the Lost Colony and in the appalling death
      rate during the early occupations at Jamestown, the first permanent English
      settlement in America.

PMID- 9554843
TI  - Tunneling into a single magnetic atom: spectroscopic evidence of the kondo
      resonance 
AB  - The Kondo effect arises from the quantum mechanical interplay between the
      electrons of a host metal and a magnetic impurity and is predicted to result in
      local charge and spin variations around the magnetic impurity. A cryogenic
      scanning tunneling microscope was used to spatially resolve the electronic
      properties of individual magnetic atoms displaying the Kondo effect.
      Spectroscopic measurements performed on individual cobalt atoms on the surface of
      gold show an energetically narrow feature that is identified as the Kondo
      resonance-the predicted response of a Kondo impurity. Unexpected structure in the
      Kondo resonance is shown to arise from quantum mechanical interference between
      the d orbital and conduction electron channels for an electron tunneling into a
      magnetic atom in a metallic host.

PMID- 9554844
TI  - Clouds of high contrast on Uranus.
AB  - Near-infrared images of Uranus taken with the Hubble Space Telescope in July and
      October 1997 revealed discrete clouds with contrasts exceeding 10 times the
      highest contrast observed before with other techniques. At visible wavelengths,
      these 10 clouds had lower contrasts than clouds seen by Voyager 2 in 1986.
      Uranus' rotational rates for southern latitudes were identical in 1986 and 1997.
      Clouds in northern latitudes rotate slightly more slowly than clouds in opposite
      southern latitudes.

PMID- 9554845
TI  - Brain activity during speaking: from syntax to phonology in 40 milliseconds.
AB  - In normal conversation, speakers translate thoughts into words at high speed. To
      enable this speed, the retrieval of distinct types of linguistic knowledge has to
      be orchestrated with millisecond precision. The nature of this orchestration is
      still largely unknown. This report presents dynamic measures of the real-time
      activation of two basic types of linguistic knowledge, syntax and phonology.
      Electrophysiological data demonstrate that during noun-phrase production speakers
      retrieve the syntactic gender of a noun before its abstract phonological
      properties. This two-step process operates at high speed: the data show that
      phonological information is already available 40 milliseconds after syntactic
      properties have been retrieved.

PMID- 9554846
TI  - Targeting the receptor-Gq interface to inhibit in vivo pressure overload
      myocardial hypertrophy.
AB  - Hormones and neurotransmitters may mediate common responses through receptors
      that couple to the same class of heterotrimeric guanine nucleotide-binding (G)
      protein. For example, several receptors that couple to Gq class proteins can
      induce cardiomyocyte hypertrophy. Class-specific inhibition of Gq-mediated
      signaling was produced in the hearts of transgenic mice by targeted expression of
      a carboxyl-terminal peptide of the alpha subunit Galphaq. When pressure overload
      was surgically induced, the transgenic mice developed significantly less
      ventricular hypertrophy than control animals. The data demonstrate the role of
      myocardial Gq in the initiation of myocardial hypertrophy and indicate a possible
      strategy for preventing pathophysiological signaling by simultaneously blocking
      multiple receptors coupled to Gq.

PMID- 9554847
TI  - Enzyme structure with two catalytic sites for double-sieve selection of
      substrate.
AB  - High-fidelity transfers of genetic information in the central dogma can be
      achieved by a reaction called editing. The crystal structure of an enzyme with
      editing activity in translation is presented here at 2.5 angstroms resolution.
      The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate
      substrate L-isoleucine but also the minimally distinct L-valine in the first,
      aminoacylation step. Then, in a second, "editing" step, the synthetase itself
      rapidly hydrolyzes only the valylated products. For this two-step substrate
      selection, a "double-sieve" mechanism has already been proposed. The present
      crystal structures of the synthetase in complexes with L-isoleucine and L-valine
      demonstrate that the first sieve is on the aminoacylation domain containing the
      Rossmann fold, whereas the second, editing sieve exists on a globular beta-barrel
      domain that protrudes from the aminoacylation domain.

PMID- 9554848
TI  - Dependence of germinal center B cells on expression of CD21/CD35 for survival.
AB  - Affinity-driven selection of B lymphocytes within germinal centers is critical
      for the development of high-affinity memory cells and host protection. To
      investigate the role of the CD21/CD35 coreceptor in B cell competition for
      follicular retention and survival within the germinal center, either Cr2+ or
      Cr2null lysozyme-specific transgenic B cells were adoptively transferred into
      normal mice immunized with duck (DEL) or turkey (TEL) lysozyme, which bind with
      different affinities. In mice injected with high-affinity turkey lysozyme,
      Cr2null B cells responded by follicular retention; however, they could not
      survive within germinal centers. This suggests that CD21 provides a signal
      independent of antigen that is required for survival of B cells in the germinal
      center.

PMID- 9554849
TI  - Visualization of single RNA transcripts in situ.
AB  - Fluorescence in situ hybridization (FISH) and digital imaging microscopy were
      modified to allow detection of single RNA molecules. Oligodeoxynucleotide probes
      were synthesized with five fluorochromes per molecule, and the light emitted by a
      single probe was calibrated. Points of light in exhaustively deconvolved images
      of hybridized cells gave fluorescent intensities and distances between probes
      consistent with single messenger RNA molecules. Analysis of beta-actin
      transcription sites after serum induction revealed synchronous and cyclical
      transcription from single genes. The rates of transcription initiation and
      termination and messenger RNA processing could be determined by positioning
      probes along the transcription unit. This approach extends the power of FISH to
      yield quantitative molecular information on a single cell.

PMID- 9554850
TI  - In situ visualization of DNA double-strand break repair in human fibroblasts.
AB  - A method was developed to examine DNA repair within the intact cell. Ultrasoft x
      rays were used to induce DNA double-strand breaks (DSBs) in defined subnuclear
      volumes of human fibroblasts and DNA repair was visualized at those sites. The
      DSBs remained in a fixed position during the initial stages of DNA repair, and
      the DSB repair protein hMre11 migrated to the sites of damage within 30 minutes.
      In contrast, hRad51, a human RecA homolog, did not localize at sites of DNA
      damage, a finding consistent with the distinct roles of these proteins in DNA
      repair.

PMID- 9554851
TI  - Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of
      Cdc45p onto chromatin.
AB  - Cdc45p, a protein essential for initiation of DNA replication, associates with
      chromatin after "start" in late G1 and during the S phase of the cell cycle.
      Binding of Cdc45p to chromatin depends on Clb-Cdc28 kinase activity as well as
      functional Cdc6p and Mcm2p, which suggests that Cdc45p associates with the
      prereplication complex after activation of S-phase cyclin-dependent kinases
      (CDKs). As indicated by the timing and the CDK dependence, binding of Cdc45p to
      chromatin is crucial for commitment to initiation of DNA replication. During S
      phase, Cdc45p physically interacts with minichromosome maintenance (MCM) proteins
      on chromatin; however, dissociation of Cdc45p from chromatin is slower than that
      of MCMs, which indicates that the proteins are released by different mechanisms.

PMID- 9554852
TI  - Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and
      GSK3beta.
AB  - Control of stability of beta-catenin is central in the wnt signaling pathway.
      Here, the protein conductin was found to form a complex with both beta-catenin
      and the tumor suppressor gene product adenomatous polyposis coli (APC). Conductin
      induced beta-catenin degradation, whereas mutants of conductin that were
      deficient in complex formation stabilized beta-catenin. Fragments of APC that
      contained a conductin-binding domain also blocked beta-catenin degradation. Thus,
      conductin is a component of the multiprotein complex that directs beta-catenin to
      degradation and is located downstream of APC. In Xenopus embryos, conductin
      interfered with wnt-induced axis formation.

PMID- 9554853
TI  - Activation of the protein kinase p38 in the spindle assembly checkpoint and
      mitotic arrest.
AB  - The mitogen-activated protein kinase (MAPK) superfamily comprises classical MAPK
      (also called ERK), c-Jun amino-terminal or stress-activated protein kinase (JNK
      or SAPK), and p38. Although MAPK is essential for meiotic processes in Xenopus
      oocytes and the spindle assembly checkpoint in Xenopus egg extracts, the role of
      members of the MAPK superfamily in M phase or the spindle assembly checkpoint
      during somatic cell cycles has not been elucidated. The kinase p38, but not MAPK
      or JNK, was activated in mammalian cultured cells when the cells were arrested in
      M phase by disruption of the spindle with nocodazole. Addition of activated
      recombinant p38 to Xenopus cell-free extracts caused arrest of the extracts in M
      phase, and injection of activated p38 into cleaving embryos induced mitotic
      arrest. Treatment of NIH 3T3 cells with a specific inhibitor of p38 suppressed
      activation of the checkpoint by nocodazole. Thus, p38 functions as a component of
      the spindle assembly checkpoint in somatic cell cycles.

PMID- 9554854
TI  - Supramolecular structure of the Salmonella typhimurium type III protein secretion
      system.
AB  - The type III secretion system of Salmonella typhimurium directs the translocation
      of proteins into host cells. Evolutionarily related to the flagellar assembly
      machinery, this system is also present in other pathogenic bacteria, but its
      organization is unknown. Electron microscopy revealed supramolecular structures
      spanning the inner and outer membranes of flagellated and nonflagellated strains;
      such structures were not detected in strains carrying null mutations in
      components of the type III apparatus. Isolated structures were found to contain
      at least three proteins of this secretion system. Thus, the type III apparatus of
      S. typhimurium, and presumably other bacteria, exists as a supramolecular
      structure in the bacterial envelope.

PMID- 9554855
TI  - A distinctive class of integron in the Vibrio cholerae genome.
AB  - The ability of bacteria to acquire and disseminate heterologous genes has been a
      major factor in the development of multiple drug resistance. A gene, intI4, was
      identified that encodes a previously unknown integrase that is associated with a
      "gene-VCR" organization (VCRs are Vibrio cholerae repeated sequences), similar to
      that of the well-characterized antibiotic resistance integrons. The similarity
      was confirmed by IntI1-mediated recombination of a gene-VCR cassette into a class
      1 integron. VCR cassettes are found in a number of Vibrio species including a
      strain of V. metschnikovii isolated in 1888, suggesting that this mechanism of
      heterologous gene acquisition predated the antibiotic era.

PMID- 9554856
TI  - The risk of a diagnosis of cancer after primary deep venous thrombosis or
      pulmonary embolism.
AB  - BACKGROUND: Several small studies have indicated an association between deep
      venous thrombosis or pulmonary embolism and a subsequent diagnosis of cancer, but
      the subject is controversial. METHODS: We conducted a nationwide study of a
      cohort of patients with deep venous thrombosis or pulmonary embolism that was
      drawn from the Danish National Registry of Patients for the years 1977 through
      1992. The occurrence of cancer in the cohort was determined by linkage to the
      Danish Cancer Registry. The expected number of cancer cases was estimated on the
      basis of national age-, sex-, and site-specific incidence rates. RESULTS: A total
      of 15,348 patients with deep venous thrombosis and 11,305 patients with pulmonary
      embolism were identified. We observed 1737 cases of cancer in the cohort with
      deep venous thrombosis, as compared with 1372 expected cases (standardized
      incidence ratio, 1.3; 95 percent confidence interval, 1.21 to 1.33). Among the
      patients with pulmonary embolism, the standardized incidence ratio was 1.3, with
      a 95 percent confidence interval of 1.22 to 1.41. The risk was substantially
      elevated only during the first six months of follow-up and declined rapidly
      thereafter to a constant level slightly above 1.0 one year after the thrombotic
      event. Forty percent of the patients given a diagnosis of cancer within one year
      after hospitalization for thromboembolism had distant metastases at the time of
      the diagnosis of cancer. There were strong associations with several cancers,
      most pronounced for those of the pancreas, ovary, liver (primary hepatic cancer),
      and brain. CONCLUSIONS: An aggressive search for a hidden cancer in a patient
      with a primary deep venous thrombosis or pulmonary embolism is not warranted.

PMID- 9554857
TI  - Topical treatment with nerve growth factor for corneal neurotrophic ulcers.
AB  - BACKGROUND: Corneal neurotrophic ulcers associated with impairment of sensory
      innervation of the cornea may lead to loss of vision, and there is no effective
      treatment for these ulcers. We evaluated the effects of nerve growth factor in
      patients with this disorder. METHODS: Twelve patients (14 eyes) with severe
      neurotrophic corneal ulcers associated with corneal anesthesia were treated with
      topical nerve growth factor 10 times daily for two days and then 6 times daily
      until the ulcers healed. Treatment continued for 2 weeks after the ulcers healed,
      and the patients were then followed for up to 12 months. The evolution of the
      corneal disease during treatment and follow-up was evaluated by slit-lamp
      examination, photography, fluorescein-dye testing, and tests of corneal
      sensitivity and best corrected visual acuity. RESULTS: Corneal healing began 2 to
      14 days after the initiation of treatment with nerve growth factor, and all
      patients had complete healing of their corneal ulcers after 10 days to 6 weeks of
      treatment. Corneal sensitivity improved in 13 eyes, and returned to normal in 2
      of the 13 eyes. Corneal integrity and sensitivity were maintained during the
      follow-up period (range, 3 to 12 months). Best corrected visual acuity increased
      progressively during treatment and follow-up in all patients. There were no
      systemic or local side effects of treatment. CONCLUSIONS: In this preliminary,
      uncontrolled study, topically applied exogenous nerve growth factor restored
      corneal integrity in patients with corneal neurotrophic ulcers.

PMID- 9554858
TI  - Relation between preoperative inspiratory lung resistance and the outcome of lung
      volume-reduction surgery for emphysema.
AB  - BACKGROUND: Surgery to reduce lung volume has recently been reintroduced to
      alleviate dyspnea and improve exercise tolerance in selected patients with
      emphysema. A reliable means of identifying patients who are likely to benefit
      from this surgery is needed. METHODS: We measured lung resistance during
      inspiration, static recoil pressure at total lung capacity, static lung
      compliance, expiratory flow rates, and lung volumes in 29 patients with chronic
      obstructive lung disease before lung-volume-reduction surgery. The changes in the
      forced expiratory volume in one second (FEV1) six months after surgery were
      related to the preoperatively determined physiologic measures. A response to
      surgery was defined as an increase in the FEV1 of at least 0.2 liter and of at
      least 12 percent above base-line values. RESULTS: Of the 29 patients, 23 had some
      improvement in FEV1 including 15 who met the criteria for a response to surgery.
      Among the variables considered, only preoperative lung resistance during
      inspiration predicted changes in expiratory flow rates after surgery. Inspiratory
      lung resistance correlated significantly and inversely with improvement in FEV1
      after surgery (r=-0.63, P<0.001). A preoperative criterion of an inspiratory
      resistance of 10 cm of water per liter per second had a sensitivity of 88 percent
      (14 of 16 patients) and a specificity of 92 percent (12 of 13 patients) in
      identifying patients who were likely to have a response to surgery. CONCLUSIONS:
      Preoperative lung resistance during inspiration appears to be a useful measure
      for selecting patients with emphysema for lung-volume-reduction surgery.

PMID- 9554859
TI  - Identification of fetal DNA and cells in skin lesions from women with systemic
      sclerosis.
AB  - BACKGROUND: Systemic sclerosis is a disease of unknown origin which often occurs
      in women after their childbearing years. It has many clinical and
      histopathological similarities to chronic graft-versus-host disease. Recent
      studies indicate that fetal stem cells can survive in the maternal circulation
      for many years post partum. This finding suggests that fetal cells persisting in
      the maternal circulation or tissues could be involved in the pathogenesis of
      systemic sclerosis by initiating a graft-versus-host reaction. METHODS: We used
      the polymerase chain reaction (PCR) to identify Y-chromosome sequences in DNA
      extracted from peripheral-blood cells and skin lesions from women with systemic
      sclerosis of recent onset. To confirm the PCR findings, we used fluorescence in
      situ hybridization of peripheral-blood cells and cells within chronic
      inflammatory-cell infiltrates in biopsy specimens of affected skin. RESULTS: Y
      chromosome sequences were found in DNA from peripheral-blood cells in 32 of 69
      women with systemic sclerosis (46 percent), as compared with 1 of 25 normal women
      (4 percent, P<0.001), and in T lymphocytes from 3 women with systemic sclerosis
      who had male offspring. Furthermore, Y-chromosome sequences were identified in
      skin-biopsy specimens from 11 of 19 women with systemic sclerosis (58 percent); 9
      of the 11 were known to have carried male fetuses. Nucleated cells containing Y
      chromosomes were detected by fluorescence in situ hybridization in paraffin
      embedded sections of skin lesions from all seven women we tested whose skin
      biopsy specimens contained Y-chromosome sequences. CONCLUSIONS: Fetal
      antimaternal graft-versus-host reactions may be involved in the pathogenesis of
      systemic sclerosis in some women.

PMID- 9554860
TI  - Images in clinical medicine. The Gaudi-colon connection.

PMID- 9554861
TI  - A national survey of physician-assisted suicide and euthanasia in the United
      States.
AB  - BACKGROUND: Although there have been many studies of physician-assisted suicide
      and euthanasia in the United States, national data are lacking. METHODS: In 1996,
      we mailed questionnaires to a stratified probability sample of 3102 physicians in
      the 10 specialties in which doctors are most likely to receive requests from
      patients for assistance with suicide or euthanasia. We weighted the results to
      obtain nationally representative data. RESULTS: We received 1902 completed
      questionnaires (response rate, 61 percent). Eleven percent of the physicians said
      that under current legal constraints, there were circumstances in which they
      would be willing to hasten a patient's death by prescribing medication, and 7
      percent said that they would provide a lethal injection; 36 percent and 24
      percent, respectively, said that they would do so if it were legal. Since
      entering practice, 18.3 percent of the physicians (unweighted number, 320)
      reported having received a request from a patient for assistance with suicide and
      11.1 percent (unweighted number, 196) had received a request for a lethal
      injection. Sixteen percent of the physicians receiving such requests (unweighted
      number, 42), or 3.3 percent of the entire sample, reported that they had written
      at least one prescription to be used to hasten death, and 4.7 percent (unweighted
      number, 59), said that they had administered at least one lethal injection.
      CONCLUSIONS: A substantial proportion of physicians in the United States report
      that they receive requests for physician-assisted suicide and euthanasia, and
      about 7 percent of those who responded to our survey have complied with such
      requests at least once.

PMID- 9554862
TI  - The nephrotic syndrome.

PMID- 9554864
TI  - Primary venous thromboembolism and cancer screening.

PMID- 9554865
TI  - Clearing the cornea with nerve growth factor.

PMID- 9554866
TI  - Microchimerism and autoimmune disease.

PMID- 9554867
TI  - (-)-6-Chloro-2-[(1-furo[2, 3-c]pyridin-5-ylethyl)thio]-4-pyrimidinamine, PNU
      142721, a new broad spectrum HIV-1 non-nucleoside reverse transcriptase
      inhibitor.

PMID- 9554868
TI  - 2-Iminohomopiperidinium salts as selective inhibitors of inducible nitric oxide
      synthase (iNOS).
AB  - An attractive approach to the treatment of inflammatory conditions such as osteo-
      and rheumatoid arthritis, inflammatory bowel disease, and sepsis is through the
      selective inhibition of human inducible nitric oxide synthase (hiNOS) since
      localized excess nitric oxide (NO) release has been implicated in the pathology
      of these diseases. A series of monosubstituted iminohomopiperidinium salts
      possessing lipophilic functionality at ring positions 3, 5, 6, and 7 has been
      synthesized, and series members have demonstrated the ability to inhibit the
      hiNOS isoform with an IC50 as low as 160 nM (7). Compounds were found that
      selectively inhibit hiNOS over the human endothelial constitutive enzyme (heNOS)
      with a heNOS/hiNOS IC50 ratio in excess of 100 and as high as 314 (9). Potencies
      for inhibition of hiNOS and the human neuronal constitutive enzyme (hnNOS) are
      comparable. Substitution in the 3 and 7 positions provides compounds that exhibit
      the greatest degree of selectivity for hiNOS and hnNOS over heNOS. Submicromolar
      potencies for 6 and 7 in a mouse RAW cell assay demonstrated the ability of these
      compounds to inhibit iNOS in a cellular environment. These latter compounds were
      also found to be orally bioavailable and efficacious due to their ability to
      inhibit the increase in plasma nitrite/nitrate levels in a rat LPS model.

PMID- 9554869
TI  - Rational drug design approach for overcoming drug resistance: application to
      pyrimethamine resistance in malaria.
AB  - Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase
      thymidylate synthase (DHFR-TS). Resistance in the most important human parasite,
      Plasmodium falciparum, initially results from an S108N mutation in the DHFR
      domain, with additional mutation (most commonly C59R or N51I or both) imparting
      much greater resistance. From a homology model of the 3-D structure of DHFR-TS,
      rational drug design techniques have been used to design and subsequently
      synthesize inhibitors able to overcome malarial pyrimethamine resistance.
      Compared to pyrimethamine (Ki 1.5 nM) with purified recombinant DHFR fromP.
      falciparum, the Ki value of the m-methoxy analogue of pyrimethamine was 1.07 nM,
      but against the DHFR bearing the double mutation (C59R + S108N), the Ki values
      for pyrimethamine and the m-methoxy analogue were 71.7 and 14.0 nM, respectively.
      The m-chloro analogue of pyrimethamine was a stronger inhibitor of both wild-type
      DHFR (with Ki 0.30 nM) and the doubly mutant (C59R +S108N) purified enzyme (with
      Ki 2.40 nM). Growth of parasite cultures of P. falciparum in vitro was also
      strongly inhibited by these compounds with 50% inhibition of growth occurring at
      3.7 microM for the m-methoxy and 0.6 microM for the m-chloro compounds with the
      K1 parasite line bearing the double mutation (S108N + C59R), compared to 10.2
      microM for pyrimethamine. These inhibitors were also found in preliminary studies
      to retain antimalarial activity in vivo in P. berghei-infected mice.

PMID- 9554870
TI  - Anti-HIV agents that selectively target retroviral nucleocapsid protein zinc
      fingers without affecting cellular zinc finger proteins.
AB  - Agents that target the two highly conserved Zn fingers of the human
      immunodeficiency virus (HIV) nucleocapsid p7 (NCp7) protein are under development
      as antivirals. These agents covalently modify Zn-coordinating cysteine thiolates
      of the fingers, causing Zn ejection, loss of native protein structure and nucleic
      acid binding capacity, and disruption of virus replication. Concentrations of
      three antiviral agents that promoted in vitro Zn ejection from NCp7 and inhibited
      HIV replication did not impact the functions of cellular Zn finger proteins,
      including poly(ADP-ribose) polymerase and the Sp1 and GATA-1 transcription
      factors, nor did the compounds inhibit HeLa nuclear extract mediated
      transcription. Selectivity of interactions of these agents with NCp7 was
      supported by molecular modeling analysis which (1) identified a common saddle
      shaped nucleophilic region on the surfaces of both NCp7 Zn fingers, (2) indicated
      a strong correspondence between computationally docked positions for the agents
      tested and overlap of frontier orbitals within the nucleophilic loci of the NCp7
      Zn fingers, and (3) revealed selective steric exclusion of the agents from the
      core of the GATA-1 Zn finger. Further modeling analysis suggests that the
      thiolate of Cys49 in the carboxy-terminal finger is the site most susceptible to
      electrophilic attack. These data provide the first experimental evidence and
      rationale for antiviral agents that selectively target retroviral nucleocapsid
      protein Zn fingers.

PMID- 9554872
TI  - Effect of steroids on DNA synthesis in an in vitro replication system: initial
      quantitative structure-activity relationship studies and construction of a non
      estrogen receptor pharmacophore.
AB  - The molecular mechanism(s) by which steroids affect carcinogenesis is an active
      area of investigation. Recent studies with a series of related steroids in an in
      vitro DNA replication system produced a wide range of effects including
      enhancement and inhibition of DNA synthesis. The HeLa cell-free system used in
      these studies did not contain estrogen receptors. Since the majority of hormone
      effects on cellular replication have been attributed to interactions with
      estrogen receptors, an alternative description of the results was required.
      Quantitative structure-activity relationships (QSARs) were used to relate the
      observed bioactivity of these steroids with their structure. The results indicate
      that the percentage of DNA replication could be related to three parameters
      according to the following equation: %DNA = 23.9(+/-3.8)Xdipact + 57.8(+/
      22.4)Hyd - 19.4(+/-10.4)Biophpi + 128.9, where Xdipact is the dipole moment on
      the X-axis, Hyd is the atomic hydrophobicity index, and Biophpi is the atomic pi
      population on the heteroatom found in the pharmacophore. For each molecule, the
      orientation of the functional groups changed the dipole moment value, and this
      descriptor was used as a selector of active conformations. A 3D-QSAR model was
      then constructed combining pharmacophoric features and global properties, and the
      active space and inactive space were defined using a Boolean volumetric
      operation.

PMID- 9554871
TI  - Modulation of receptor and receptor subtype affinities using diastereomeric and
      enantiomeric monosaccharide scaffolds as a means to structural and biological
      diversity. A new route to ether synthesis.
AB  - We show that carbohydrates constitute an attractive source of readily available,
      stereochemically defined scaffolds for the facile attachment of side chains
      contained in genetically encoded and other amino acids. beta-D- and beta-L
      glucose, L-mannose, and the 6-deoxy-6-N-analogue of beta-D-glucose have been
      employed to synthesize peptidomimetics that bind the SRIF receptors on AtT-20
      mouse pituitary cells, five cloned human receptor subtypes (hSSTRs), and the NK-1
      receptor. The affinity profile of various sugar-based ligands at the hSSTRs is
      compared with that of SRIF. Compound 19 bound hSSTR4 with a Ki of 100 nM. Subtle
      structural changes affect affinities. Evidence is presented that suggests that
      one compound (8) binds both the AtT-20 cell receptors and the five hSSTRs via a
      unique mode. The SARs of the glycosides at SRIF receptors differ markedly from
      those at the NK-1 receptor. For example a 4-benzyl substituent is important for
      SRIF receptor binding, but the 4-desbenzyl analogue 27 was highly potent (IC50 of
      27 nM) at the NK-1 receptor. A new, nonbasic method for the synthesis of base
      sensitive ethers from primary and secondary alcohols is also described.

PMID- 9554873
TI  - Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p
      isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP
      resistant tumor cell lines. Interaction of these complexes with DNA.
AB  - The reaction of p-isopropylbenzaldehyde thiosemicarbazone [p-is.TSCN], 1, with
      palladium(II) acetate and potassium tetrachloroplatinate yielded two tetrameric
      orthopalladated isomers, [Pd(p-is.TSCN)]4 (complexes 2 and 3), and the platinum
      analogue [Pt(p-is.TSCN)]4 (complex 4), respectively. All of these complexes
      contain the thiosemicarbazone bonded as a terdentate ligand to the metallic atom,
      through the thiol sulfur, the azomethinic nitrogen and the ortho carbon of the p
      isopropylphenyl ring to which the imine group is attached to as deduced from the
      study of the IR, NMR, and XRD spectra of complexes 2 and 4. Complexes 2 and 4
      crystallize in the centrosymmetric monoclinic space group C2/c, with Z = 8. Unit
      cell parameters for complex 2 are as follows: a = 25.742(5) A, b = 19.560(4) A, c
      = 24.199(5) A, beta = 101.70(3)o. Unit cell parameters for complex 4 are as
      follows: a = 25.8728(19) A, b = 19. 5053(14) A, c = 24.0899(16) A, beta =
      101.305(2)o. As can be deduced from the NMR study, the palladated isomers 2 and 3
      interconvert in DMSO which may be a consequence of the existence in both
      complexes of a flexible eight-membered ring with alternating Pd-S atoms. The
      testing of the cytotoxic activity of these compounds against several human and
      murine cell lines sensitive and resistant to cisplatin (cis-DDP) suggests that
      compounds 2, 3, and 4 may be endowed with important anticancer properties since
      they elicit IC50 values in the microM range as does the clinically used drug cis
      DDP, and, moreover, they display cytotoxic activity in tumor lines resistant to
      cis-DDP. The analysis of the interaction of these novel tetrameric cyclometalated
      compounds with DNA suggests that they form DNA interhelical cross-links.

PMID- 9554874
TI  - Synthesis and biological activities of tricyclic conformationally restricted
      tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate
      reductases.
AB  - The synthesis of seven 2,4-diamino-5,6,7,8-tetrahydro-7-substituted
      pyrido[4',3':4,5]furo[2,3-d]pyrimidines 1-6 are reported as nonclassical
      antifolate inhibitors of dihydrofolate reductase (DHFR) and compound 7 as a
      classical antifolate inhibitor of tumor cells in culture. The compounds were
      designed as conformationally restricted analogues of trimetrexate. The synthesis
      was accomplished from the cyclocondensation of 3-bromo-4-piperidone with 2, 4
      diamino-6-hydroxypyrimidine to afford regiospecifically 2, 4-diamino-5,6,7,8
      tetrahydropyrido[4',3':4,5]furo[2, 3-d]pyrimidine-7-hydrobromide (16). This in
      turn was alkylated with the appropriate benzyl halide to afford the target
      compounds 1-6. The classical antifolate 7 utilized 4-(chloromethyl)benzoyl-l
      glutamic acid diethyl ester (17) instead of the benzyl halide for alkylation,
      followed by saponification to afford 7. Compounds 1-6 showed moderate inhibitory
      potency against DHFR from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium
      avium, and rat liver. The classical analogue 7 was 88-fold more potent against M.
      avium DHFR than against rat liver DHFR. The classical analogue was also
      inhibitory against the growth of tumor cells, CCRF-CEM, and FaDu, in culture.

PMID- 9554875
TI  - cycloSal-2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (cycloSal-d4TMP):
      synthesis and antiviral evaluation of a new d4TMP delivery system.
AB  - The synthesis, hydrolysis, and antiviral evaluation of novel, lipophilic cycloSal
      d4TMP derivatives 3a-h of the anti-HIV dideoxynucleoside 2',3'-dideoxy-2',3'
      didehydrothymidine (d4T, 1) are reported. This pro-nucleotide concept has been
      designed to deliver d4TMP (2) by selective chemical hydrolysis. All compounds 3a
      h were synthesized using phosphorus(III) chemistry in good yields and in somewhat
      lower yields using phosphorus(V) chemistry starting from substituted salicyl
      alcohols 6a-h. The phosphotriesters 3 were obtained without stereochemical
      preference with respect to the configuration at the phosphorus center as 1:1
      diastereomeric mixtures. However, a few of the triesters 3 could be separated
      into the diastereomers by means of semipreparative HPLC. In a 1-octanol/phosphate
      buffer mixture, all compounds 3 exhibited 9-100-fold higher lipophilicity as
      judged from their Pa values as compared to d4T (1). Furthermore, in hydrolysis
      studies 3 decomposed under mild aqueous basic conditions releasing solely d4TMP
      (2) and the diols 6 following the designed tandem reaction sequence. A
      correlation of the electronic properties introduced by the substituents and the
      half-lives of triesters 3 was observed. Thus, by varying the substituent, the
      half-lives of 3 could be adjusted over a wide range of compounds still delivering
      d4TMP (2) selectively. Phosphotriesters 3 exhibited considerable activity against
      HIV-1 and HIV-2 in wild-type human T-lymphocyte (CEM/O) cells as well as mutant
      thymidine kinase-deficient (CEM/TK-) cells. Surprisingly, we observed a 3-80-fold
      difference in antiviral activity between the two diastereomers. Our data clearly
      prove that the cycloSal-d4TMPs deliver exclusively the nucleotide d4TMP not only
      under simulated hydrolysis conditions but also under cellular conditions and thus
      fulfill the thymidine kinase-bypass premise. Therefore, the cycloSal-nucleotide
      concept is the first reported pro-nucleotide system that delivers the
      dideoxynucleotide by a pH-driven, chemically activated, tandem reaction without
      the requirement of an enzymatic contribution.

PMID- 9554876
TI  - Synthesis and structure-activity relationships of carboxyflavones as structurally
      rigid CysLT1 (LTD4) receptor antagonists.
AB  - The synthesis and CysLT1 receptor affinities of a new series of highly rigid 3'-
      and 4'-(2-quinolinylmethoxy)- or 3'- and 4'-[2-(2-quinolinyl)ethenyl]
      substituted, 6-, 7-, or 8-carboxylated flavones are described. CysLT1 receptor
      affinities of the flavones (down to 11 nM) were determined by their ability to
      displace [3H]LTD4 from its receptor in guinea pig lung membranes. Structure
      affinity relationship studies showed that the relative positions of the
      carboxylic acid and the quinoline moiety were critical for CysLT1 affinities.
      While the carboxyl is optimal in the 8 position but tolerated in the 6 position,
      only the 6- and not the 8-tetrazole has significant activity. The quinoline
      moiety may be connected to the flavone skeleton by an ethenyl or a methoxy
      linker, but the substitution position is important for high affinity, especially
      in the 6-carboxylated flavones. 4'-Substituted 6-carboxyflavones are essentially
      inactive, whereas the 3'-substituted analogues have submicromolar CysLT1
      affinity. Replacement of the quinoline by other heteroaromates generally leads to
      decreased affinities, with the phenyl and naphthyl analogues displaying only
      little or no affinity, while the 7-chloroquinoline analogue is comparable in
      activity to the quinoline. Flavones having CysLT1 receptor affinities of 10-30 nM
      were selected for determination of their inhibitory effects on the LTD4-induced
      contraction of guinea pig ileum in vitro. The IC50 values ranged between 15 and
      100 nM. Compound 5d (8-carboxy-6-chloro-3'-(2-quinolinylmethoxy)flavone, VUF
      5087) was selected for further research because of its high potency in the
      functional assay. This series contains the most rigid CysLT1 receptor antagonists
      known to date, and they are useful in the development of a CysLT1 antagonist
      model, which is discussed in the companion paper.

PMID- 9554877
TI  - Development of a three-dimensional CysLT1 (LTD4) antagonist model with an
      incorporated amino acid residue from the receptor.
AB  - This paper describes the molecular modeling of leukotriene CysLT1 (or LTD4)
      receptor antagonists. Several different structural classes of CysLT1 antagonists
      were superimposed onto the new and highly rigid CysLT1 antagonist 8-carboxy-3'-[2
      (2-quinolinyl)ethenyl]flavone (1, VUF 5017) to generate a common pharmacophoric
      arrangement. On the basis of known structure-activity relationships of CysLT1
      antagonists, the quinoline nitrogen (or a bioisosteric equivalent thereof) and an
      acidic function were taken as the matching points. In order to optimize the
      fitting of acidic moieties of all antagonists, an arginine residue from the
      receptor was proposed as the interaction site for the acidic moieties.
      Incorporation of this amino acid residue into the model revealed additional
      interactions between the guanidine group and the nitrogen atoms of quinoline
      containing CysLT1 antagonists. In some cases, the arginine may even interact with
      pi-clouds of phenyl residues of CysLT1 antagonists. The alignment of Montelukast
      (MK-476) suggests the presence of an additional pocket in the binding site for
      CysLT1 antagonists. The derived model should be useful for a better understanding
      of the molecular recognition of the leukotriene CysLT1 receptor.

PMID- 9554878
TI  - Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis,
      structure-activity relationships, and X-ray crystal structure studies.
AB  - Comparison of the high-resolution X-ray structures of the native HIV-1 protease
      and its complexes with the inhibitors suggested that the enzyme flaps are
      flexible. The movement at the tip of the flaps could be as large as 7 A. On the
      basis of this observation, cyclic cyanoguanidines have been designed,
      synthesized, and evaluated as HIV-1 protease (PR) inhibitors. Cyclic
      cyanoguanidines were found to be very potent inhibitors of HIV-1 protease. The
      choice of cyclic cyanoguanidines over cyclic guanidines was based on the reduced
      basicity of the former. X-ray structure studies of the HIV PR complex with cyclic
      cyanoguanidine demonstrated that in analogy to cyclic urea, cyclic
      cyanoguanidines also displace the unique structural water molecule. The structure
      activity relationship of the cyclic cyanoguanidines is compared with that of the
      corresponding cyclic urea analogues. The differences in binding constants of the
      two series of compounds have been rationalized using high-resolution X-ray
      structure information.

PMID- 9554880
TI  - Conformation-function relationship of vitamin D: conformational analysis predicts
      potential side-chain structure.
AB  - In previous studies, we have grouped regions in space occupied by the vitamin D
      side chain into four: A, G, EA, and EG. We showed that the receptor (VDR)
      affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side
      chain region, in the order EG, G, A, and EA. We called this the active space
      group concept. In the present study, we used this active space group concept to
      analyze the conformation-activity relationship of about 40 representative potent
      1alpha,25-dihydroxyvitamin D3 analogues. We initially listed structural
      modifications in the side chain of potent vitamin D analogues and estimated their
      potency factor. Possible side-chain conformations of representative analogues
      were calculated by the molecular mechanics method and plotted on a dot map
      compared with the regions A, G, EA, and EG. The cell-differentiating potency of
      the analogues was correlated with our active space group concept with few
      exceptions. Among potent analogues with a natural configuration at C(20), the
      side chains of those with a 22-oxa, 22-ene, 16-ene, or a 18-nor modification were
      located in front of region EA (termed F). The side chains of the most potent 20
      epi-22-oxa-24-homovitamin D analogues were concentrated at the left side of the
      EA region (L-EA). Thus, the side chains of almost all potent analogues were
      distributed around the EA region, and potency increased in the order A, F, EA,
      and L-EA.

PMID- 9554879
TI  - Human P2Y1 receptor: molecular modeling and site-directed mutagenesis as tools to
      identify agonist and antagonist recognition sites.
AB  - The molecular basis for recognition by human P2Y1 receptors of the novel,
      competitive antagonist 2'-deoxy-N6-methyladenosine 3', 5'-bisphosphate (MRS 2179)
      was probed using site-directed mutagenesis and molecular modeling. The potency of
      this antagonist was measured in mutant receptors in which key residues in the
      transmembrane helical domains (TMs) 3, 5, 6, and 7 were replaced by Ala or other
      amino acids. The capacity of MRS 2179 to block stimulation of phospholipase C
      promoted by 2-methylthioadenosine 5'-diphosphate (2-MeSADP) was lost in P2Y1
      receptors having F226A, K280A, or Q307A mutations, indicating that these residues
      are critical for the binding of the antagonist molecule. Mutation of the residues
      His132, Thr222, and Tyr136 had an intermediate effect on the capacity of MRS 2179
      to block the P2Y1 receptor. These positions therefore appear to have a modulatory
      role in recognition of this antagonist. F131A, H277A, T221A, R310K, or S317A
      mutant receptors exhibited an apparent affinity for MRS 2179 that was similar to
      that observed with the wild-type receptor. Thus, Phe131, Thr221, His277, and
      Ser317 are not essential for antagonist recognition. A computer-generated model
      of the human P2Y1 receptor was built and analyzed to help interpret these
      results. The model was derived through primary sequence comparison, secondary
      structure prediction, and three-dimensional homology building, using rhodopsin as
      a template, and was consistent with data obtained from mutagenesis studies. We
      have introduced a "cross-docking" procedure to obtain energetically refined 3D
      structures of the ligand-receptor complexes. Cross-docking simulates the
      reorganization of the native receptor structure induced by a ligand. A putative
      nucleotide binding site was localized and used to predict which residues are
      likely to be in proximity to agonists and antagonists. According to our model TM6
      and TM7 are close to the adenine ring, TM3 and TM6 are close to the ribose
      moiety, and TM3, TM6, and TM7 are near the triphosphate chain.

PMID- 9554881
TI  - Clarification of the binding mode of teleocidin and benzolactams to the Cys2
      domain of protein kinase Cdelta by synthesis of hydrophobically modified,
      teleocidin-mimicking benzolactams and computational docking simulation.
AB  - Phorbol esters (12-O-tetradecanoylphorbol 13-acetate; TPA) and teleocidins are
      known to be potent tumor promoters and to activate protein kinase C (PKC) by
      binding competitively to the enzyme. The relationship between the chemical
      structures and the activities of these compounds has attracted much attention
      because of the marked structural dissimilarities. The benzolactam 5, with an
      eight-membered lactam ring and benzene ring instead of the nine-membered lactam
      ring and indole ring of teleocidins, reproduces the active ring conformation and
      biological activities of teleocidins. Herein we describe the synthesis of
      benzolactams with hydrophobic substituents at various positions. Structure
      activity data indicate that the existence of a hydrophobic region between C-2 and
      C-9 and the steric factor at C-8 play critical roles in the appearance of
      biological activities. We also computationally simulated the docking of
      teleocidin and the modified benzolactam molecules to the Cys2 domain structure
      observed in the crystalline complex of PKCdelta with phorbol 13-acetate.
      Teleocidin and benzolactams fitted well into the same cavity as phorbol 13
      acetate. Of the three functional groups hydrogen-bonding to the protein, two
      hydrogen-bonded with protein atoms in common with phorbol 13-acetate, but the
      third one hydrogen-bonded with a different protein atom from that in the case of
      phorbol 13-acetate. The model explains well the remarkable difference in activity
      between 5 and its analogue having a bulky substituent at C-8.

PMID- 9554882
TI  - Membrane-induced secondary structures of neuropeptides: a comparison of the
      solution conformations adopted by agonists and antagonists of the mammalian
      tachykinin NK1 receptor.
AB  - We present what we believe to be the first documented example of an inducement of
      distinctly different secondary structure types onto agonists and antagonists
      selective for the same G-coupled protein receptor using the same membrane-model
      matrix wherein the induced structures are consistent with those suggested to be
      biologically active by extensive analogue studies and conventional binding
      assays. 1H NMR chemical shift assignments for the mammalian NK1 receptor
      selective agonists alpha-neurokinin (NKA) and beta-neurokinin (NKB) as well as
      the mammalian NK1 receptor-selective antagonists [d-Pro2,d-Phe7,d-Trp9]SP and [d
      Arg1, d-Pro2,d-Phe7,d-His9]SP have been determined at 600 MHz in sodium dodecyl
      sulfate (SDS) micelles. The SDS micelle system simulates the membrane-interface
      environment the peptide experiences when in the proximity of the membrane
      embedded receptor, allowing for conformational studies that are a rough
      approximation of in vivo conditions. Two-dimensional NMR techniques were used to
      assign proton resonances, and interproton distances were estimated from the
      observed nuclear Overhauser effects (NOEs). The experimental distances were used
      as constraints in a molecular dynamics and simulated annealing protocol using the
      modeling package DISCOVER to generate three-dimensional structures of the two
      agonists and two antagonists when present in a membrane-model environment to
      determine possible prebinding ligand conformations. It was determined that (1)
      NKA is helical from residues 6 to 9, with an extended N-terminus; (2) NKB is
      helical from residues 4 to 10, with an extended N-terminus; (3) [d-Pro2,d-Phe7,d
      Trp9]SP has poorly defined helical properties in the midregion and a beta-turn
      structure in the C-terminus (residues 6-9); and (4) [d-Arg1,d-Pro2, d-Phe7,d
      His9]SP has a helical structure in the midregion (residues 4-6) and a well
      defined beta-turn structure in the C-terminus (residues 6-10). Attempts have been
      made to correlate the observed conformational differences between the agonists
      and antagonists to their binding potencies and biological activity.

PMID- 9554883
TI  - Therapeutic effects of monoclonal antibody-beta-lactamase conjugates in
      combination with a nitrogen mustard anticancer prodrug in models of human renal
      cell carcinoma.
AB  - A panel of 13 renal cell carcinoma cell lines was evaluated for the expression of
      antigens recognized by the L6 and L49 monoclonal antibodies. All of the cell
      lines were strongly positive for the L6 antigen, and 9/13 bound 96.5, which, like
      the L49 monoclonal antibody, recognizes the p97 melanotransferrin antigen. The L6
      and L49 antibodies were chemically conjugated to Enterobacter cloacae beta
      lactamase (bL), and their abilities to effect site-selective anticancer prodrug
      activation on two of the renal cell carcinoma cell lines (SN12P and 1934J) were
      evaluated in vitro and in vivo. L49-bL was 10-90-fold more potent in vitro than
      L6-bL for the activation of 7-(4-carboxybutanamido)cephalosporin mustard (CCM), a
      cephalosporin prodrug of phenylenediamine mustard (PDM). In addition, L49-bL
      showed higher degrees of specific SN12P and 1934J intratumoral uptake than L6-bL,
      even though the expression of L6 antigen was 2-fold higher than that of p97.
      These differences might be due to the high-affinity antigen binding of L49-bL
      relative to L6-bL. In vivo studies utilizing nude mice with established
      subcutaneous SN12P and 1934J tumor xenografts demonstrated that L49-bL/CCM
      combinations led to regressions and cures at well-tolerated doses, while L6
      bL/CCM and the nonbinding control conjugate P1.17-bL in combination with CCM were
      ineffective. Conjugate localization in 1934J tumors was much lower than that
      observed in SN12P tumors, a finding that might acount for the higher activities
      of L49-bL/CCM in the latter model. These data show that the p97 antigen on renal
      cell carcinomas can be exploited for selective prodrug activation, even on tumors
      that localize very small amounts of the L49-bL conjugate.

PMID- 9554885
TI  - Synthesis and biological activity of chimeric structures derived from the
      cytotoxic natural compounds dolastatin 10 and dolastatin 15.
AB  - The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities
      in structure and in their biological activity profiles. Two compounds (1 and 2)
      formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal
      Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible
      equivalence of these units. These compounds can be considered as chimeras of
      dolastatins 10 and 15 formed by the N-terminal part of the former and the C
      terminal part of the latter and vice versa. Both analogues exhibited a marked
      decrease in their cytotoxic activity but showed similar differential cytotoxicity
      with regard to the cell lines assayed compared with the parent compounds. HT-29
      cell line was the least sensitive one. However, this activity was in the
      nanomolar level and close to that of vincristine. The differences in their effect
      on tubulin polymerization were less pronounced. We confirmed the already known
      crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit
      and the MeVal-Pro dipeptide probably reflects modification in the relative
      positions of the N-dimethylamino and the phenyl moieties.

PMID- 9554884
TI  - Design and synthesis of potent, selective inhibitors of endothelin-converting
      enzyme.
AB  - Endothelin-1 is the most potent peptidic vasoconstrictor discovered to date. The
      final step of posttranslational processing of this peptide is the conversion of
      its precursor by endothelin-converting enzyme-1 (ECE-1), a metalloprotease which
      displays high amino acid sequence identity with neutral endopeptidase 24.11 (NEP)
      especially at the catalytic center. A series of potent and selective
      arylacetylene-containing ECE-1 inhibitors have been prepared. (S, S)-3-Cyclohexyl
      2-[[5-(2, 4-difluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino] propio
      nic acid (47), an arylacetylene amino phosphonate dipeptide, was found to inhibit
      ECE-1 and NEP with IC50 values of 14 nM and 2 microM, respectively. Similarly,
      (S)-[[1-[(2-biphenyl-4-ylethyl)carbamoyl]-4-(2-fluorophenyl)but-3- yny
      l]amino]methyl]phosphonic acid (56), an arylacetylene amino phosphonate amide,
      had IC50's of 33 nM and 6.5 microM for ECE-1 and NEP, respectively. Slight
      modification of the aryl moiety was found to have dramatic effects on ECE-1/NEP
      selectivity. The 2-fluoro dipeptide analogue, (S, S)-2-[[5-(2-fluorophenyl)-2
      [(phosphonomethyl)amino]pent-4-ynoyl]+ ++amin o]-4-methylpentanoic acid (40),
      showed a 72-fold selectivity for ECE-1 over NEP, while the 3-fluoro dipeptide
      analogue, (S, S)-2-[[5-(3-fluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]+
      ++amin o]-4-methylpentanoic acid (22), was equipotent for ECE-1 and NEP. Several
      of these inhibitors were shown to be potent in blocking ET-1 production in vivo
      as demonstrated by the big ET-1-induced pressor response in rats. These potent
      inhibitors are the most selective for ECE-1 reported to date and are envisaged to
      have a variety of therapeutic applications.

PMID- 9554886
TI  - Nuclease-resistant composite 2',5'-oligoadenylate-3', 5'-oligonucleotides for the
      targeted destruction of RNA: 2-5A-iso-antisense.
AB  - A new modification of 2-5A-antisense, 2-5A-iso-antisense, has been developed
      based on a reversal of the direction of the polarity of the antisense domain of a
      2-5A-antisense composite nucleic acid. This modification was able to anneal with
      its target RNA as well as the parental 2-5A-antisense chimera. The 2-5A-iso
      antisense oligonucleotide displayed enhanced resistance to degradation by 3'
      exonuclease enzyme activity such as that represented by snake venom
      phosphodiesterase and by that found in human serum. 2-5A-Iso-antisense was able
      to effect the degradation of a synthetic nontargeted substrate, [5'-32P]pC11U2C7,
      and two targeted RNAs, PKR and BCR mRNAs, in a cell-free system containing
      purified recombinant human 2-5A-dependent RNase L. These results demonstrated
      that the novel structural modification represented by 2-5A-iso-antisense provided
      a stabilized biologically active formulation of the 2-5A-antisense strategy.

PMID- 9554887
TI  - Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi.
AB  - Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related
      structures were designed, synthesized, and evaluated as antiproliferative agents
      against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class
      of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety
      replacing selected aromatic protons by different groups via electrophilic
      aromatic substitution reactions as well as introducing a sulfur atom at the polar
      extreme. Of the designed compounds, sulfur-containing derivatives were shown to
      be potent antireplicative agents against T. cruzi. Among these drugs, 4
      phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active
      growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC50 of
      2.2 microM. Under the same assay conditions, this drug was much more active than
      Nifurtimox, one of the drugs currently in clinical use to control this disease.
      This thiocyanate derivative was also a very active inhibitor against the
      intracellular form of the parasite at the nanomolar level. Other sulfur
      derivatives prepared also exhibited very potent antiproliferative action against
      T. cruzi. The presence of a sulfur atom at the polar extreme for this family of
      compounds seems to be very important for biological action because this atom was
      always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate
      presents very good prospective not only as a lead drug but also as a potential
      chemotherapeutic agent.

PMID- 9554890
TI  - Antibiotic resistance: an increasing problem?. It always has been, but there are
      things we can do.

PMID- 9554891
TI  - Drugs in British prisons. Policies need outside scrutiny if they are to do more
      good than harm.

PMID- 9554892
TI  - Leukotriene modifiers in the treatment of asthma. Look promising across the board
      of asthma severity.

PMID- 9554893
TI  - Functional neurosurgery for Parkinson's disease. Has come a long way, though much
      remains experimental.

PMID- 9554894
TI  - Developing the BMJ's coverage of basic science. We are introducing science
      commentaries 

PMID- 9554895
TI  - Medical and psychosocial effects of early discharge after surgery for breast
      cancer: randomised trial.
AB  - OBJECTIVE: To assess the medical and psychosocial effects of early hospital
      discharge after surgery for breast cancer on complication rate, patient
      satisfaction, and psychosocial outcomes. DESIGN: Randomised trial comparing
      discharge from hospital 4 days after surgery (with drain in situ) with discharge
      after drain removal (mean 9 days in hospital). Psychosocial measurements
      performed before surgery and 1 and 4 months after. SETTING: General hospital and
      cancer clinic in Rotterdam with a socioeconomically diverse population. SUBJECTS:
      125 women with operable breast cancer. MAIN OUTCOME MEASURES: Incidence of
      complications after surgery for breast cancer, patient satisfaction with
      treatment, and psychosocial effects of short stay or long stay in hospital.
      RESULTS: Patient satisfaction with the short stay in hospital was high; only 4%
      (2/56 at 1 month after surgery and 2/52 at 4 months after surgery) of patients
      indicated that they would have preferred a longer stay. There were no significant
      differences in duration of drainage from the axilla between the short stay and
      long stay groups (median 8 v 9 days respectively, P=0.45) or the incidence of
      wound complications (10 patients v 9 patients). The median number of seroma
      aspirations per patient was higher for the long stay group (1 v 3.5, P=0.04).
      Leakage along the drain occurred more frequently in short stay patients (21 v 10
      patients, P=0.04). The two groups did not differ in scores for psychosocial
      problems (uncertainty, anxiety, loneliness, disturbed sleep, loss of control,
      threat to self esteem), physical or psychological complaints, or in the coping
      strategies used. Before surgery, short stay patients scored higher on scales of
      depression (P=0.03) and after surgery they were more likely to discuss their
      disease with their families (at 1 month P=0.004, at 4 months P=0.04).
      CONCLUSIONS: Early discharge from hospital after surgery for breast cancer is
      safe and is well received by patients. Early discharge seems to enhance the
      opportunity for social support within the family.

PMID- 9554896
TI  - Resolution of peanut allergy: case-control study.
AB  - OBJECTIVES: To determine whether there are any differences between children who
      remain mildly or moderately allergic to peanut and children with similar
      histories but a negative reaction on challenge with peanut. DESIGN: Case-controls
      matched for age and sex. SETTING: Children's day wards in two teaching hospitals.
      INTERVENTION: Open food challenge with peanut. SUBJECTS: 15 children with
      resolved peanut allergy (resolvers) and 15 with persistent allergy (persisters).
      MAIN OUTCOME MEASURE: Reaction on challenge with peanut, serum total and peanut
      specific IgE concentrations. RESULTS: The groups had a similar median age at
      first reaction to peanut (11 months, range 5-38) and similar symptoms. Allergy to
      other foods was less common in resolvers (2/15) than persisters (9/15) (P=0.02).
      On skin prick testing with peanut all 13 resolvers tested but only 3/14
      persisters had a weal of <6 mm (P<0.0001). Total and peanut specific IgE
      concentrations did not differ much between the groups. CONCLUSION: Appropriately
      trained clinicians must be prepared to challenge preschool children with peanut
      as some will be tolerant despite a history of reactions to peanut and a positive
      skin prick test with peanut. Preschool children whose apparent peanut allergy is
      refuted by food challenge show allergy to other foods less often than those in
      whom peanut allergy persists. The size of weal on skin prick testing to peanut
      predicts reactivity but not severity on peanut challenge.

PMID- 9554898
TI  - Alternative definitions 

PMID- 9554900
TI  - The new NHS: 38,534 doctors disapprove 

PMID- 9554897
TI  - Effectiveness of antibiotic prophylaxis in critically ill adult patients:
      systematic review of randomised controlled trials.
AB  - OBJECTIVE: To determine whether antibiotic prophylaxis reduces respiratory tract
      infections and overall mortality in unselected critically ill adult patients.
      DESIGN: Meta-analysis of randomised controlled trials from 1984 and 1996 that
      compared different forms of antibiotic prophylaxis used to reduce respiratory
      tract infections and mortality with aggregate data and, in a subset of trials,
      data from individual patients. SUBJECTS: Unselected critically ill adult
      patients; 5727 patients for aggregate data meta-analysis, 4343 for confirmatory
      meta-analysis with data from individual patients. MAIN OUTCOME MEASURES:
      Respiratory tract infections and total mortality. RESULTS: Two categories of
      eligible trials were defined: topical plus systemic antibiotics versus no
      treatment and topical preparation with or without a systemic antibiotic versus a
      systemic agent or placebo. Estimates from aggregate data meta-analysis of 16
      trials (3361 patients) that tested combined treatment indicated a strong
      significant reduction in infection (odds ratio 0.35; 95% confidence interval 0.29
      to 0.41) and total mortality (0.80; 0.69 to 0.93). With this treatment five and
      23 patients would need to be treated to prevent one infection and one death,
      respectively. Similar analysis of 17 trials (2366 patients) that tested only
      topical antibiotics indicated a clear reduction in infection (0.56; 0.46 to 0.68)
      without a significant effect on total mortality (1.01; 0.84 to 1.22). Analysis of
      data from individual patients yielded similar results. No significant differences
      in treatment effect by major subgroups of patients emerged from the analyses.
      CONCLUSIONS: This meta-analysis of 15 years of clinical research suggests that
      antibiotic prophylaxis with a combination of topical and systemic drugs can
      reduce respiratory tract infections and overall mortality in critically ill
      patients. This effect is significant and worth while, and it should be considered
      when practice guidelines are defined.

PMID- 9554899
TI  - Identifying asthma and chronic obstructive pulmonary disease in patients with
      persistent cough presenting to general practitioners: descriptive study.
AB  - OBJECTIVE: To determine the prevalence of asthma and chronic obstructive
      pulmonary disease in patients not known to have these disorders, who present in
      general practice with persistent cough, and to ascertain criteria to help general
      practitioners in diagnosis. DESIGN: Descriptive study. SETTING: Primary
      healthcare centre in the Netherlands. SUBJECTS: 192 patients aged 18-75 years,
      not known to have asthma or chronic obstructive pulmonary disease, attending
      their general practitioner with cough persisting for at least 2 weeks. : A
      diagnosis of asthma or chronic obstructive pulmonary disease was based on the
      recurrence of airway symptoms in the past year accompanied by spirometric
      measurements (including bronchodilator testing) and methacholine provocation
      tests. A scoring formula to estimate the probability of asthma or chronic
      obstructive pulmonary disease, based on history and physical examination, was
      generated by means of logistic regression. RESULTS: 74 patients (39%) were
      classified as having asthma, 14 (7%) as having chronic obstructive pulmonary
      disease. The best formula for predicting asthma or chronic obstructive pulmonary
      disease used scores for three symptoms: (reported) wheeze, (reported) dyspnoea,
      and allergen induced symptoms, together with prolonged expiration, pack years of
      smoking, and female sex. Variables were scored 1 when present and 0 when absent,
      except for allergen induced symptoms (1.5) and number of pack years of smoking
      (n/25). With a cut off value of 3 on the scoring formula, 76% of the patients
      could be classified correctly. CONCLUSIONS: About half of patients with
      persistent cough who present to a general practitioner have asthma or chronic
      obstructive pulmonary disease. With a simple formula based on three symptoms and
      prolonged expiration, pack years of smoking, and female sex, most patients may be
      identified correctly in general practice.

PMID- 9554901
TI  - Rethinking NHS networking.

PMID- 9554903
TI  - Food allergy.

PMID- 9554902
TI  - Adverse drug reactions.

PMID- 9554905
TI  - Truth drug 

PMID- 9554906
TI  - Development and importance of health needs assessment.

PMID- 9554907
TI  - The dying adult.

PMID- 9554908
TI  - How should different life expectancies be valued?

PMID- 9554904
TI  - North of England evidence based guideline development project: guideline on the
      use of aspirin as secondary prophylaxis for vascular disease in primary care.
      North of England Aspirin Guideline Development Group.

PMID- 9554909
TI  - Carers of patients receiving palliative care. Social workers bring specialist
      skills to care of carers.

PMID- 9554910
TI  - New combined hepatitis A and B vaccine. Risks Of viral hepatitis related to
      travel.

PMID- 9554911
TI  - Topical treatment of erectile dysfunction did not show results.

PMID- 9554912
TI  - Authors defend their study to develop tool to predict falls in elderly people.

PMID- 9554913
TI  - Deaths related to intrapartum asphyxia. Audit In one unit found neonatal care to
      be suboptimal at weekends.

PMID- 9554914
TI  - Second study shows that octreotide may prevent early rebleeding in cirrhosis.

PMID- 9554915
TI  - New government, same narrow vision. How hospitals manage emergency admissions
      needs to be examined.

PMID- 9554916
TI  - Ways of assessing capacity to complete an advance directive should be developed.

PMID- 9554917
TI  - All troops sent to gulf should be randomised to receive anthrax vaccination or
      placebo.

PMID- 9554918
TI  - Doctors should beware of asking for too high a salary. Scottish GPs earn less
      than intended average net remuneration.

PMID- 9554919
TI  - Britain needs 1000 more GPs 

PMID- 9554920
TI  - What rough beast? 

PMID- 9554921
TI  - Last on the list 

PMID- 9554923
TI  - Early discharge after surgery for breast cancer may be beneficial 

PMID- 9554922
TI  - Trust me, I'm a wreck doctors at large, an 11 part series on BBC2, looks at how a
      group of doctors have fared 14 years on from their acceptance at medical school.
      David fitzmaurice says future medics should be forced to watch the series in one
      sitting 

PMID- 9554924
TI  - Peanut allergy may resolve in some young children 

PMID- 9554925
TI  - Antibiotic prophylaxis in critically ill patients is clinically effective 

PMID- 9554926
TI  - Scoring system identifies asthma in patients with persistent cough 

PMID- 9554927
TI  - NHS networking needs a new approach 

PMID- 9554928
TI  - Evidence for aspirin as secondary prophylaxis for vascular disease is strong 

PMID- 9554929
TI  - Prognostic significance of pathological response of primary tumor and metastatic
      axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast
      carcinoma.
AB  - PURPOSE: The prognostic significance of pathological response of primary tumor
      and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed
      in patients with noninflammatory locally advanced breast carcinoma. PATIENTS AND
      METHODS: Between January 1989 and April 1995, 148 consecutive patients with
      locally advanced breast carcinoma participated in the study. Of these, 140 fully
      evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three
      courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by
      modified radical mastectomy when technically feasible or definitive radiation
      therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients
      were postmenopausal. RESULTS: Objective response was recorded in 99 of 140
      patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred
      in 11 patients (8%), and partial response occurred in 88 patients (63%). No
      change was recorded in 37 patients (26%), and progressive disease occurred in 4
      patients (3%). One hundred and thirty-six patients underwent the planned surgery.
      Maximal pathological response of the primary tumor (in situ carcinoma or minimal
      microscopic residual tumor) was observed in 24 (18%); 112 patients (82%)
      presented minimal pathological response of the primary tumor (gross residual
      tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy
      was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62
      patients (45%). Considering the initial TNM status, 75% of the patients had
      decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23%
      of patients with clinical N1 and N2, respectively, showed uninvolved axillary
      lymph nodes. A significant correlation was noted between pathological response of
      primary tumor and the number of metastatic axillary lymph nodes. Median disease
      free survival was 34 months, whereas median overall survival was 66 months.
      Pathological responses of both primary tumor and metastatic axillary lymph nodes
      were strongly correlated with disease-free survival and overall survival in
      univariate analyses. Additionally, in a proportional hazard regression model and
      in an accelerated failure time model, metastatic axillary lymph nodes
      significantly influenced both disease-free survival and overall survival, whereas
      pathological response of primary tumor did so on disease-free survival only.
      CONCLUSION: After neoadjuvant chemotherapy, pathological responses of both
      primary tumor and metastatic axillary lymph nodes had a marked prognostic
      significance and influenced outcome for patients with locally advanced breast
      carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of
      potentially involved axillary nodes may represent a major goal of neoadjuvant
      chemotherapy. Further studies are warranted to clarify whether these results
      reflect the therapeutic effect or intrinsic biologic factors of the tumor.

PMID- 9554930
TI  - The generation of proton electrochemical potential gradient by cytochrome c
      oxidase.
AB  - Cytochrome c oxidase, the terminal oxidase of mitochondria and some bacteria,
      catalyzes the four electron reduction of oxygen, and generates a proton
      electrochemical potential gradient (Delta microH). The recently determined
      structures of the bacterial and the bovine enzymes, together with studies of site
      directed mutants of a bacterial cytochrome c oxidase and a closely related
      ubiquinol oxidase, have greatly advanced our understanding of the mechanism by
      which oxygen reduction is coupled to the generation of Delta microH. Two
      different mechanisms contribute to the generation of Delta microH: protons that
      are consumed by the reduction of oxygen, are taken exclusively from the
      mitochondrial matrix ('consumed' protons), while other protons are translocated
      by the enzyme across the membrane ('pumped' protons). It is suggested that both
      proton consumption and proton pumping are driven by the electrostatic charging of
      the enzyme reaction center by the reducing electrons. Proton consumption is
      suggested to result from the electrostatically driven ejection of hydroxyls into
      the matrix that is catalyzed by a tyrosine residue in the reaction center. Proton
      pumping is suggested to result from the electrostatically driven translocation of
      a glutamate residue near the reaction center, and is assisted by secondary
      acceptors that release the translocated protons.

PMID- 9554931
TI  - Transient changes of electrical activity in the rat barrel cortex during
      conditioning.
AB  - To reveal the dynamics of neurophysiological changes in the rat barrel cortex
      induced by conditioned stimulation we recorded the local micro
      electroencephalographic (EEG) activity and evoked potentials (EPs) in barrel
      cortex to stimulation of a single vibrissa before and after pairing it with a
      mild electric shock applied to the rat's tail. Following the introduction of the
      reinforcing stimulus, the amplitude of the first negative component of evoked
      potentials in the cortex on the conditioned side grew in relation to the same
      component of control potentials, evoked by stimulation of the opposite
      symmetrical vibrissa. This change was accompanied by a latent decrease in
      spectral power of the EEG within the alpha and beta frequency bands in both
      hemispheres. The observed changes in both of these electrical manifestations of
      enhanced neuronal activity reverted after two (EP) or three (EEG) days of
      conditioning. These results are discussed in relation to the putative activity of
      neuromodulatory systems.

PMID- 9554932
TI  - Short-term and complete reversal of NGF effects in rats with lesions of the
      nucleus basalis magnocellularis.
AB  - Rats received bilateral quisqualic acid lesions of the nucleus basalis
      magnocellularis. Three weeks after lesioning, osmotic minipumps were implanted
      that released recombinant human nerve growth factor or cytochrome c at a dosage
      of 5.0 microg rat-1 day-1 through intracerebroventricular cannulas for 7 weeks.
      One quarter of the rats were sacrificed at the end of the treatment, while the
      rest of the animals were sacrificed 2, 8, and 12 weeks after termination of
      NGF/cc treatment. ICV administration of nerve growth factor (NGF) transiently
      reduced weight gain. NGF maximally increased choline acetyltransferase activity
      in all cortical regions, the olfactory bulb and the hippocampus between 20% and
      56% at the end of the treatment. This increase linearly declined and completely
      regressed during the 12-week withdrawal period both in regions affected and
      unaffected by the lesion. Administration of NGF induced a short-lasting
      hypertrophy of low affinity NGF receptor immunoreactive neurons within the
      nucleus basalis magnocellularis (NBM), the horizontal limb of the diagonal band
      of Broca, and the medial septum. In contrast, QUIS-induced NBM lesions
      permanently reduced ChAT activity most pronounced in the frontal and parietal
      cortex up to 45%. Furthermore, QUIS induced a permanent loss of p75NGFr
      immunoreactive neurons within the NBM and the DB without affecting the MS. These
      findings suggest that degenerating cholinergic neurons of the NBM and HDB do not
      spontaneously recover after lesioning and may require continuous neurotrophic
      support by NGF to ameliorate cholinergic hypofunctioning.

PMID- 9554933
TI  - POU domain genes are differentially expressed in the early stages after lineage
      commitment of the PNS-derived stem cell line, RT4-AC.
AB  - RT4 is a family of cell lines derived from a rat peripheral neurotumor and
      consists of a multipotential stem cell which spontaneously gives rise to a glial
      derivative and two neuronal derivatives. To begin to understand the role(s) of
      transcription factors in neural differentiation, we examined the expression of
      ten transcription factor genes (MASH1, REST/NRSF, Oct-1, Oct-2, Tst-1/SCIP, Brn
      1, Brn-2, Brn-3.0, Brn-4, Brn-5) in the RT4 cell lines. We report here that all
      of the RT4 cells express REST/NRSF, Oct-1 and Brn-5, but do not express MASH1,
      Brn-3.0 or Brn-4. Furthermore, Brn-2 and Tst-1/SCIP expression was restricted to
      the RT4 stem cell line and glial derivative, while Oct-2 was expressed
      predominantly by the RT4 stem cell line and neuronal derivatives. We propose that
      the lack of expression of MASH1 (which is expressed relatively early in autonomic
      neuron differentiation) and Brn-3.0 (which is expressed early in sensory neuron
      differentiation), in combination with the presence of REST/NRSF (a repressor of
      neuronal gene expression), in all of the RT4 cell lines, establishes the RT4
      system as a unique model for examining very early events in neuronal versus glial
      cell fate determination.

PMID- 9554934
TI  - A role for brain glucocorticoid receptors in contextual fear conditioning:
      dependence upon training intensity.
AB  - We studied the possible involvement of corticosteroids in the establishment and
      long-term expression of contextual fear conditioning and questioned whether a
      corticosteroid action might be dependent upon stimulus intensity at training.
      Experiments included: (i) the intracerebroventricular administration of specific
      antagonists for the two types of intracellular corticosteroid receptors to rats
      trained at either 1 mA or 0.4 mA shock intensity at conditioning; and (ii) the
      administration of corticosterone after conditioning rats to 0.2 mA shocks. The
      results showed that the administration of a type II glucocorticoid, but not a
      type I mineralocorticoid, receptor antagonist before conditioning rats to the
      intermediate shock condition attenuated long-term expression of contextual fear
      conditioning. However, treatment with the antagonists before conditioning to the
      high shock intensity failed to influence the extent of fear conditioning. In
      addition, an intraperitoneal corticosterone injection, given immediately after
      training rats at the low shock intensity, enhanced long-term expression of the
      fear response. The results support the view that post-training levels of
      circulating corticosterone, through an interaction with central type II
      glucocorticoid receptors, modulate the strength to which memory for contextual
      fear conditioning is established and maintained.

PMID- 9554935
TI  - Distribution of somatostatin-like immunoreactivity in the brain of the frog, Rana
      esculenta, during development.
AB  - The anatomical distribution of somatostatin-like immunoreactivity in the central
      nervous system of the frog, Rana esculenta, during development and in juvenile
      specimens was investigated by indirect immunofluorescence. Soon after hatching,
      at stages II-III, somatostatin-like immunoreactive structures were found in the
      preoptic-median eminence complex. In stage VI tadpoles, new groups of
      immunopositive perikarya and nerve fibers appeared in the diencephalon, within
      the ventral infundibular nucleus and in the ventral area of the thalamus, as well
      as in the medial pallium. In stages XII-XIV of development, immunopositive
      perikarya were also present in the dorsal infundibular nucleus of the
      hypothalamus and ventrolateral area of the thalamus. A small group of
      somatostatin-like immunoreactive neurons appeared in the posteroventral nucleus
      of the rhombencephalon. However, these neurons were not seen in later stages of
      development. Tadpoles in stages XVIII, XXI-XXII and in juveniles were
      characterized by a wider distribution of immunoreactive cell bodies and fibers in
      the pallium. New groups of immunoreactive neurons were found in the dorsal and
      lateral pallium. The presence of positive perikarya in the lateral pallium is a
      transient expression found only in these stages. The organization of the
      somatostatinergic system was most complex during the metamorphic climax, with the
      appearance of positive cell bodies in the posterocentralis area of the thalamus,
      and in juvenile animals with the presence of perikarya in the ventral part of the
      medial pallium and within the central grey rhombencephali. In contrast to the
      adult frog, somatostatin neurons were not observed in the mesencephalon of
      tadpoles and juveniles.

PMID- 9554936
TI  - Tactile hyperesthesia, altered epidermal innervation and plantar nerve injury in
      the hindfeet of rats housed on wire grates.
AB  - The effects of wire grates on nerve injury and recovery were examined in rats
      housed in cages with sawdust-covered solid flooring. For the first 3 weeks of the
      study, 20 rats were housed on sawdust alone and 20 rats were housed in cages with
      wire grates placed over the sawdust. For the remaining 9 weeks, 10 animals housed
      on sawdust had wire grates added to their cages, while grates were removed from
      the cages of 10 animals. The effects of tactile stimulation on hindpaw plantar
      skin was measured weekly using the Von Frey filament test. Intraepidermal
      innervation using PGP 9.5 immunostaining and plantar nerve histology were
      assessed at the end of the 12-week study. After just 1 week on grates, hindpaw
      withdrawal thresholds were already markedly decreased and remained low until the
      grates were removed at 3 weeks. Thresholds returned to normal by 4 weeks after
      removal of the grates. Wire grates also induced increases in PGP 9.5
      immunoreactive intraepidermal fine nerve endings that were normalized after grate
      removal. Demyelination, Wallerian degeneration and Renaut bodies were induced in
      the medial plantar nerve in rats housed in cages with wire-grate flooring. Nerve
      injury was largely resolved after 9 weeks on sawdust flooring. These data
      demonstrate that wire grates rapidly induce hindpaw tactile hyperesthesia and
      plantar neuropathy in rats and emphasize a risk of using wire-grate cage flooring
      in studies assessing hindlimb function and structure.

PMID- 9554937
TI  - Photosynthetic rhizobia 

PMID- 9554938
TI  - Pitch vs. spectral encoding of harmonic complex tones in primary auditory cortex
      of the awake monkey.
AB  - Neuromagnetic studies in humans and single-unit studies in monkeys have provided
      conflicting views regarding the role of primary auditory cortex (A1) in pitch
      encoding. While the former support a topographic organization based on the pitch
      of complex tones, single-unit studies support the classical tonotopic
      organization of A1 defined by the spectral composition of the stimulus. It is
      unclear whether the incongruity of these findings is due to limitations of
      noninvasive recordings or whether the discrepancy genuinely reflects pitch
      representation based on population encoding. To bridge these experimental
      approaches, we examined neuronal ensemble responses in A1 of the awake monkey
      using auditory evoked potential (AEP), multiple-unit activity (MUA) and current
      source density (CSD) techniques. Macaque monkeys can perceive the missing
      fundamental of harmonic complex tones and therefore serve as suitable animal
      models for studying neural encoding of pitch. Pure tones and harmonic complex
      tones missing the fundamental frequency (f0) were presented at 60 dB SPL to the
      ear contralateral to the hemisphere from which recordings were obtained. Laminar
      response profiles in A1 reflected the spectral content rather than the pitch
      (missing f0) of the compound stimuli. These findings are consistent with single
      unit data and indicate that the cochleotopic organization is preserved at the
      level of A1. Thus, it appears that pitch encoding of multi-component sounds is
      more complex than suggested by noninvasive studies, which are based on the
      assumption of a single dipole generator within the superior temporal gyrus. These
      results support a pattern recognition mechanism of pitch encoding based on a
      topographic representation of stimulus spectral composition at the level of A1.

PMID- 9554939
TI  - Antagonism of peripheral 5-HT4 receptors reduces visceral and cutaneous pain in
      mice, and induces visceral analgesia after simultaneous inactivation of 5-HT3
      receptors.
AB  - The role of 5-HT4 receptors on cutaneous and visceral pain remains largely
      unexplored. The objective of this study was to establish the activity profile of
      SDZ 205-557, a 5-HT4 antagonist, on cutaneous (hotplate) and visceral (writhing)
      models of pain, after peripheral administration. Since SDZ 205-557 possesses some
      affinity for 5-HT3 receptors at high doses, nociceptive effects of a 1:1
      combination of SDZ 205-557 and MDL 72222, a 5-HT3 antagonist, were also
      evaluated. Drugs were injected 30 min before tests (0, 0.001, 0.01, 0.1 or 1
      mg/kg IP). A hypoalgesic effect of SDZ 205-557 on cutaneous pain was found at 0.1
      and 1 mg/kg doses, as revealed through an enhanced nociceptive threshold in rats
      placed on the hotplate. This effect was likely mediated through inactivation of
      peripheral 5-HT4 receptors. After the 1:1 combination, the hypoalgesic effect
      disappeared, which indicates that simultaneous inactivation of 5-HT3 and 5-HT4
      receptors antagonized peripherally 5-HT4-mediated hypoalgesia by an unknown
      mechanism. SDZ 205-557 also induced hypoalgesia in the writhing test over the
      entire dose range tested, and visceral hypoalgesia turned out to be analgesia
      after 1:1 combination. In summary, findings of the present study imply that: i)
      antagonism of 5-HT4 receptors mediates antinociception in enteric viscera and, to
      a lesser extent, in cutaneous terminals, and ii) dual inactivation of both 5-HT4
      and 5-HT3 receptors induces visceral analgesia, a fact which might have clinical
      importance.

PMID- 9554940
TI  - Onset of optic nerve conduction and synaptic potentials in superior colliculus of
      fetal rats studied in vitro.
AB  - This article describes the onset of electrical excitability and synaptic
      transmission in the retinocollicular pathway of the fetal and early postnatal
      rat, utilizing a novel in vitro preparation. Although the optic nerve is visible
      in embryonic day (E) 14 brain, its stimulation produced no response in the
      superior colliculus (SC) until E16 when a low voltage simple negative wave was
      evoked. At E17 these potentials were blocked rapidly, completely, and reversibly
      when choline was substituted for sodium or with the addition of cobalt ions. In
      the course of establishing the block with either of the above agents the latency
      of response increased, indicating an action on axonal transmission. By E20 the
      collicular evoked potential showed a short followed by a longer latency wave. The
      latter was blocked by the glutamate antagonist kynurenic acid, with latency
      unaffected. Further examination of potentials with the addition of glutamatergic
      receptor subtype blockers aminophosphonopentanoic acid (APV) and 6-cyano-7
      nitroquinoxaline-2,3-dione/6,7-dinitroquinoxaline- 2,3-dione (CNQX/DNQX) showed a
      clear abolition of the elicited potentials by E20 and older. Thus, fetal rat
      optic nerve fibers are capable of conduction in response to electrical
      stimulation as soon as they reach the SC at E16. Both sodium and calcium are
      involved. GABA-mediated modulation of axonal conduction is evident by E18.
      Glutaminergic synaptic transmission is established by E20. The timetable of fetal
      onset of capability to conduct and support synaptic transmission in the
      retinocollicular pathway is earlier than had previously been reported in vivo in
      the rat in which the superior colliculus neurones are said not to be driven by
      the optic nerve until 6 days post natal. This has relevance to the possible role
      of impulse activity in development of the pathway.

PMID- 9554941
TI  - Neutrophil inhibitory factor treatment of focal cerebral ischemia in the rat.
AB  - The present study was designed to determine whether a hookworm-derived
      recombinant neutrophil inhibitory factor (rNIF) is neuroprotective when
      administered after initiation of focal cerebral ischemia in the rat. We measured
      the rNIF dose-response on cerebral infarct volume, the therapeutic time window,
      the therapeutic response to permanent ischemia, and whether rNIF treatment delays
      the maturation of the ischemic lesion (2 days), or reduces cerebral infarct
      volume at 7 days after middle cerebral artery occlusion (MCAO). MCAO was induced
      by an insertion of intraluminal 4-0 monofilament nylon suture into internal
      carotid artery (n=195). We demonstrate a significant neuroprotective effect of
      rNIF administration 48 h after MCAO in a dose-dependent fashion when treatment
      was initiated upon reperfusion after 2 h MCAO and maintained until 48 h after
      MCAO. The beneficial effect was lost under conditions of permanent MCAO. The
      therapeutic time window is 4 h after MCAO. Brief treatment (6 h) is not
      sufficient to provide protection for the final ischemic damage. Continuous
      treatment with a high dose of rNIF for a long duration (7 days) is necessary to
      achieve maximum neuroprotection.

PMID- 9554943
TI  - A re-estimation of the number of glomeruli and mitral cells in the olfactory bulb
      of rabbit.
AB  - Although morphological characteristics of mammalian olfactory bulb (OB) are well
      documented in rodents (rat, mice), only one study has been performed in rabbit,
      which is also commonly used in olfactory research. The study carried out by
      Allison and Warwick in 1949 led to surprising results still quoted in recent
      literature. The present study re-examined this question in young rabbit OB, while
      it was also conducted with rat as control. In five animals of each species, areas
      and coordinates of glomeruli and mitral profiles were measured in 10 coronal
      sections uniformly distributed along the rostrocaudal axis of the OB, and a
      distribution-free stereological method was used to compute values along this
      axis. For glomeruli, the estimated number was 4200 in rat and 6300 in rabbit.
      While this estimation matched with those found in literature in rat, it
      strikingly differed from the Allison and Warwick's value of 1900 only. For mitral
      cell number, we found 59,600 while the preceding study found 45,000 only. In
      contrast to the number of glomeruli, the mitral cell number in rat and rabbit
      were very close. Indeed, results showed 56, 200 in rat. The results suggest that
      the numbers of olfactory glomeruli and mitral cells has been previously
      underestimated in rabbit, and that the number of glomeruli changes as a function
      of species. In addition, both the results of the present study and reports in the
      literature suggest the number of mitral cells to be rather similar in mouse, rat
      and rabbit. As a consequence, the glomerular/mitral cell ratio is likely to
      varied in a wide range across species.

PMID- 9554942
TI  - Behavioral inhibition of light-induced circadian phase resetting is phase and
      serotonin dependent.
AB  - Circadian rhythms in Syrian hamsters can be phase shifted by light exposure
      during the subjective night and by a bout of wheel running induced during the
      subjective day. Interactions between photic and behavioral stimuli were examined
      by comparing phase shifts to 15 min, 50 lux light pulses with and without a bout
      of running induced by confinement to a novel wheel 30 min prior to and extending
      through light exposure. Light pulses 6 h after dark onset on the first night of
      constant dark induced phase advance shifts averaging 80 min. Wheel running
      attenuated these shifts by 45% on average (p<0.01). Light pulses 1 h or 2.25 h
      after dark onset induced phase delay shifts averaging 50 min and 20 min,
      respectively, that were not affected by stimulated running. A significant running
      response to the novel wheel was evident at all 3 time points, but was greater to
      wheel confinement at both times early in the night. Stimulated running alone
      early or late in the night did not produce significant phase shifts. Behavioral
      attenuation of phase advances to light late in the night was prevented by
      pretreatment with the general 5HT1 antagonist metergoline (2 mg/kg i.p.).
      Metergoline did not significantly attenuate running in novel wheels. These
      results indicate that modulation of light-induced phase shifts by behavior is
      phase dependent and may involve direct or indirect actions of serotonin within
      the circadian system.

PMID- 9554944
TI  - Roles of the bradyrhizobium japonicum terminal oxidase complexes in microaerobic
      H2-dependent growth 
AB  - Spectral, inhibitor, and O2-consumption studies on membranes from free-living and
      bacteroid forms of Bradyrhizobium japonicum have revealed the existence of a
      number of terminal oxidases, and four terminal oxidase gene clusters within the
      heme-copper cytochrome family have been cloned. Here the complexes encoded by
      coxMNOP and coxWXYZ, genes with homology to CuA-containing cytochrome c oxidases
      and b-type ubiquinol oxidases respectively, are studied by analysis of mutants in
      each of the two oxidases and a double mutant in both of the terminal oxidase
      genes. Membranes from microaerobically incubated strain JHK12 (which contains an
      insertion in coxWXYZ) were deficient in levels of CO-reactive heme b, and both
      strains JHK12 and Bj3430 (the latter lacks coxMNOP) were deficient in CN-
      reactive cytochrome b. Membranes of the double mutant (strain JHKS4) retained
      less than 7% of the cytochrome b3 and 25% of the total CN--reactive cytochrome b
      of the wild type. Cyanide inhibition curves of oxygen uptake by wild-type
      membranes were triphasic, and only the phases inhibited by the highest (at about
      50 &mgr;M CN-, attributed to cytochrome aa3) and the lowest (at approximately 0.1
      &mgr;M) CN- were identifiable in the membranes from the two individual oxidase
      mutants. Membrane respiratory activity of the double mutant was resistant to CN-
      over a broad inhibitor concentration in the micromolar range. Consistent with our
      findings that these oxidases are expressed when cells are incubated in a low O2
      environment, the double mutant was severely deficient in H2-dependent
      chemolithotrophic growth. The latter growth condition requires prolonged
      incubation in an atmosphere of H2, CO2, and a low (1% or less) partial pressure
      of oxygen. The double mutant was also deficient in whole cell O2 dependent H2
      oxidation, with H2 uptake rates 31% of the wild type. Copyright 1998 Elsevier
      Science B.V.

PMID- 9554945
TI  - Conditioned release of corticosterone by contextual stimuli associated with
      cocaine is mediated by corticotropin-releasing factor.
AB  - Elevated blood concentrations of corticosterone (CORT), an adrenal steroid
      associated with stress responses, is one of the endocrine correlates of cocaine
      treatment. Experiment 1 confirmed and extended previous findings that chronic
      cocaine treatment does not alter corticosteroid responses to cocaine. In
      Experiment 2, conditioned endocrine effects of cocaine were examined in three
      groups of rats after 7 consecutive days of treatment. Cocaine-induced
      conditioning was achieved using a simple contextual design. In group 1 (paired),
      rats were injected with cocaine (30 mg/kg), then immediately placed into a
      locomotor activity chamber for 30 min. One hour after the rats were returned to
      their home cages, they received an injection of saline. In group 2 (unpaired),
      rats were injected with saline, then immediately placed into a locomotor activity
      chamber for 30 min. One hour after the rats were returned to their home cages,
      they received an injection of cocaine (30 mg/kg). Rats in group 3 (control)
      received only saline injections, but otherwise were treated as animals in the
      other treatment groups. On the test day (Day 8), all rats were placed immediately
      into the locomotor apparatus for 30 min prior to collection of a blood sample.
      Blood CORT concentrations and locomotor activity in the paired group were
      significantly higher than in the unpaired and control groups. However,
      pretreatment of the rats in Experiment 3 with the corticotropin-releasing factor
      (CRF) antagonist, alpha-helical CRF9-41 (1 microg, i.c.v.), on the test day,
      prior to exposure to cocaine-associated contextual cues, attenuated the
      subsequent conditioned increase in blood CORT concentrations. These data
      represent the first demonstration of classical conditioning of a steroid hormone
      response to stimuli associated with a psychoactive drug in rats and suggest that
      the effect is mediated by endogenous CRF. Because the hypothalamic-pituitary
      adrenal (HPA) axis has been implicated in modulating the actions of cocaine, it
      is plausible that such conditioned increases in CORT release by cocaine
      associated cues may further predispose an organism to the reinforcing effects of
      the drug or enhance the susceptibility to drug-taking behavior. Alternatively,
      such conditioned effects may be related to the anxiogenic properties of cocaine.
      Further understanding of the conditioned effects of hormones in the development
      and expression of addictive behaviors may provide new insights into treatment of
      drug addiction.

PMID- 9554946
TI  - Hippocampal nitric oxide synthase in the fetal guinea pig: effects of chronic
      prenatal ethanol exposure.
AB  - The effects of chronic maternal administration of ethanol on nitric oxide
      synthase (NOS) activity and the numbers of NOS containing neurons, and CA1 and
      CA3 pyramidal neurons in the hippocampus of the near term fetal guinea pig at
      gestational day (GD) 62 were investigated. Pregnant guinea pigs received oral
      administration of 4 g ethanol/kg maternal body weight (n = 5), isocaloric
      sucrose/pair feeding (n = 5) or water (n = 5), or no treatment (NT; n = 5) from
      GD 2 to GD 61. NOS activity in the 25,000 x g supernatant of hippocampal
      homogenate was determined using a radiometric assay. The numbers of NOS
      containing neurons, and CA1 and CA3 pyramidal neurons were determined using NADPH
      diaphorase histochemistry and cresyl violet staining, respectively. The chronic
      ethanol regimen produced a maternal blood ethanol concentration of 193 +/- 13
      mg/dl at 1 h after the second divided dose on GD 57. Chronic ethanol exposure
      produced fetal body, brain, and hippocampal growth restriction and decreased
      fetal hippocampal NOS activity compared with the isocaloric sucrose/pair feeding,
      water, and NT experimental groups, but did not affect the number of NOS
      containing and CA1 or CA3 pyramidal neurons. These data demonstrate that, in the
      near term fetus, chronic maternal administration of ethanol suppresses
      hippocampal NOS activity and consequent formation of NO, without loss of NOS
      containing neurons and prior to loss of CA1 pyramidal neurons that occurs in the
      adult.

PMID- 9554948
TI  - Thermoluminescence measurements on chloride-depleted and calcium-depleted
      photosystem II 
AB  - Photosystem II (PSII) in which O2 evolution was inhibited by depletion of either
      chloride or calcium ions was studied by thermoluminescence (TL) and luminescence
      (L) measurements in the presence and absence of 3-(3',4'-dichlorophenyl)-1,1
      dimethyl urea (DCMU). Cl--depleted PSII gives rise to TL and L signals which are
      similar to those in untreated controls i.e., DCMU shifts the TL band from 30
      degreesC to 8 degreesC and suppresses the L component with t1/2=10-15 s. In Ca2+
      depleted PSII a TL-band at around 50 degreesC and a slow luminescence decay
      (t1/2=60 s) is observed. Under these conditions, DCMU does not lead to a
      downshift of the peak temperature of the TL-band nor does it accelerate the decay
      kinetics of the luminescence. This indicates that in Ca2+-depleted PSII the QA/QB
      electron transfer is inhibited prior to the addition of DCMU while in Cl-
      depleted PSII QA/QB electron transfer seems unaffected. These results are
      consistent with previous fluorescence measurements which showed that the midpoint
      potential of the redox couple QA/QA- is unchanged in Cl--depleted PSII compared
      to the control while in Ca2+-depleted PSII it is shifted towards a more positive
      value [A. Krieger, A.W. Rutherford, Biochim. Biophys. Acta, 1319 (1997) 91-98].
      In the literature there are several conflicting reports concerning the TL in Ca2+
      and Cl--depleted material so we attempted to understand the origin of some of
      these discrepancies. We find that in the absence of cryoprotectants, excitation
      of TL at low temperatures leads to an upshift of TL-bands in Cl--depleted PSII,
      both in the presence and absence of DCMU, while the peak temperature of TL-bands
      in control and Ca2+-depleted PSII are downshifted. When TL is excited at 20
      degreesC or at low temperature in the presence of a cryoprotectant then there was
      no shift of the peak temperature of TL-bands. These unexpected results suggest
      that the formation of the charge pair triggers modifications in its environment
      and that the exact nature of these modifications differs depending on the
      temperature of excitation. It seems that once these modifications have occurred
      at a given temperature they remain 'locked in' being unaffected by subsequent
      temperature changes until charge recombination has occurred. Copyright 1998
      Elsevier Science B.V.

PMID- 9554947
TI  - Distribution of the endothelial constitutive nitric oxide synthase in the
      developing rat brain: an immunohistochemical study.
AB  - The present study deals with the distribution of endothelial constitutive nitric
      oxide synthase (ecNOS) in the developing rat brain using optimized protocols for
      preparation and fixation and the tyramide-signal-amplification technique. The
      immunostaining patterns of a monoclonal antibody against ecNOS are compared with
      results obtained with a rat pan-endothelial marker, the monoclonal RECA-1
      antibody. It is shown that ecNOS is present in the endothelial lining of all
      types of blood vessels and the choroid plexuses of the rat brain from the
      beginning of vasculogenesis at embryonic day 11 until adulthood (75 weeks). The
      same is true for RECA-1 immunoreactivity, that was demonstrated in the
      developmental brain vasculature for the first time. Both antigens expressed
      identical immunostaining patterns. At all investigated stages of brain
      development neither ecNOS negative blood vessels nor ecNOS positive non
      endothelial cells, e.g., neurons, were found. The data indicate that ecNOS is
      involved in the embryonic angiogenesis and the regulation of hemodynamic
      functions of brain vasculature throughout the individual life.

PMID- 9554949
TI  - Selective activation of carotid nerve fibers by acetylcholine applied to the cat
      petrosal ganglion in vitro.
AB  - The petrosal ganglion innervates carotid body chemoreceptors through the carotid
      (sinus) nerve. These primary sensory neurons are activated by transmitters
      released from receptor (glomus) cells, acetylcholine (ACh) having been proposed
      as one of the transmitters involved in this process. Since the perikarya of
      primary sensory neurons share several properties with peripheral sensory endings,
      we studied the electrical responses of the carotid nerve and glossopharyngeal
      branch to ACh locally applied to the cat petrosal ganglion superfused in vitro.
      Ganglionar applications of AChCl (1 microg-1 mg) generated bursts of action
      potentials conducted along the carotid nerve, while only a few spikes were
      exceptionally recorded from the glossopharyngeal branch in response to the
      largest doses. Carotid nerve responses to ACh were dose-dependent, the higher
      doses inducing transient desensitization. Application of nicotine to the petrosal
      ganglion also evoked dose-dependent excitatory responses in the carotid nerve.
      Responses to ACh were reversibly antagonized by adding hexamethonium to the
      superfusate, more intense and prolonged block of ACh responses being produced by
      mecamylamine. Ganglionar applications of gamma-amino butyric acid and serotonin,
      in doses of up to 5 mg, did not induce firing of action potentials in any of the
      branches of the glossopharyngeal nerve. Our results indicate that petrosal
      ganglion neurons projecting through the carotid nerve are selectively activated
      by ACh acting on nicotinic ACh receptors located in the somata of these neurons.
      Thus, cholinosensitivity would be shared by the membranes of peripheral endings
      and perikarya of primary sensory neurons involved in arterial chemoreception.

PMID- 9554950
TI  - Calcitonin gene-related peptide: distribution and effects on spontaneous rhythmic
      activity in embryonic chick spinal cord.
AB  - Immunohistochemical and in vitro electrophysiological techniques were utilized to
      examine the distribution and possible role of calcitonin gene-related peptide
      (CGRP) in the spinal cord of the developing chick. CGRP-like immunoreactivity
      first appeared in the lateral motor column of the lumbosacral spinal cord at
      embryonic day 6 followed by the emergence of fiber immunoreactivity in the dorsal
      horn at embryonic day 11. A rostrocaudal survey of the cervical to lumbosacral
      spinal cord in embryonic day 18 chick demonstrated robust CGRP-like
      immunoreactivity at all levels in both putative motor neurons and dorsal horn
      fibers. Additionally, small immunoreactive lamina VII neurons were observed in
      sections of lumbosacral cord. In the embryonic day 10 (E10) in vitro reduced
      spinal cord preparation, bath application of the calcitonin gene-related peptide
      antagonist human alpha-CGRP fragment 8-37 decreased the frequency and increased
      the duration of episodes of spontaneously occurring rhythmic activity.
      Conversely, application of alpha or beta forms of calcitonin gene-related peptide
      increased the frequency of the rhythmic episodes. The electrophysiological
      results suggest there is a constitutive release of calcitonin gene-related
      peptide contributing to the spontaneous rhythmic activity. Immunohistochemical
      results from E10 animals suggest that CGRP-like immunoreactive putative
      motoneurons may be the source of the released CGRP.

PMID- 9554951
TI  - Selective chemokine mRNA expression following brain injury.
AB  - Injury in non-neuronal tissues stimulates chemokine expression leading to
      recruitment of inflammatory cells responsible for orchestration of repair
      processes. The signals involved in directing repair of damage to the brain are
      less well understood. We hypothesized that following brain injury, chemokines are
      expressed and regulate the rate and pattern of inflammatory cell accumulation.
      The two chemokine subfamilies are alpha(alpha)-chemokines, which primarily
      function as neutrophil chemoattractants, and the beta(beta)-chemokines, which
      function primarily as monocyte chemoattractants. We assessed alpha and beta
      chemokine mRNA expression patterns and leukocyte accumulation following a
      cerebral cortical lesion. Cortical lesions were produced with and without
      addition of endotoxin, Escherichia coli lipopolysaccharide (LPS), which
      stimulates cytokine expression. We studied the expression of the beta-chemokines:
      monocyte chemoattractant protein (gene product JE; MCP-1/JE), macrophage
      inflammatory protein-1 alpha and beta (MIP-1alpha and MIP-1beta), and the
      regulated upon activation normal T expressed and secreted chemokine (RANTES) as
      well as the alpha-chemokines: interferon-gamma-inducible protein (IP-10) and
      N51/KC (KC; a murine homologue of MIP-2). Changes in gene expression were
      analyzed by Northern analysis at different time points following injury.
      Leukocyte and macrophage densities were analyzed by immunohistochemistry at the
      same time intervals. All chemokines were elevated following cortical
      injury/endotoxin. MCP-1 and MIP-1alpha were elevated at 2 h and peaked 6 h, MIP
      1beta peaked at 6 h, but declined more rapidly than MCP-1 or MIP-1alpha, and IP
      10 peaked at 6 h and showed the most rapid decline. KC was elevated at 1 h, and
      peaked at 6 h following LPS. RANTES was elevated at 1 h and achieved a plateau
      level between 6 and 18 h, then declined. In contrast, sterile injuries produced
      in the absence of endotoxin only induced the mRNA of the beta-chemokine MCP-1,
      and its expression was delayed compared to the cortical injury/endotoxin group.
      The presence of chemokine message as early as 1 h indicates that expression of
      this class of molecules is an early response in the repair process following
      traumatic brain injury. Macrophage/microglia accumulation occurred more rapidly,
      activated microglia further from the lesion border, and more cells accumulated in
      cortical injury/endotoxin than in cortical lesions produced under sterile
      conditions. Thus, there was a positive correlation between beta-chemokine
      expression and the number of beta-chemokine responsive cells (i.e. microglia)
      accumulating in injury sites. This is the first comprehensive study using a panel
      of chemokine probes and specific marcophage/microglial markers to study in vivo
      activation of the brain following injury. Our data show that the brain is capable
      of expression of multiple chemokine genes upon appropriate stimulation (e.g. LPS
      treatment). The gradient of microglial activation is consistent with physical
      damage stimulating release of chemokines that diffuse from the injury site. These
      data strongly suggest that chemokines are instrumental in the initiation of
      repair processes following brain injury.

PMID- 9554952
TI  - High-voltage electroencephalogram spindles in rats, aging and 5-HT2 antagonism.
AB  - We examined the effects of serotonin-2 (5-hydroxytryptamine-2, 5-HT2) receptor
      antagonists on the so-called high-voltage spindles (HVS, electroencephalographic
      patterns, characterized by large amplitude rhythmic waves mainly in the alpha
      band), recorded from the frontal cortex of young, middle-aged and old freely
      moving rats during waking immobility. The study was based on the assumption that
      the effects of 5-HT2 receptor antagonists on the HVS activity depend on the age
      of rats, because there is evidence for an age-related decrease in the 5-HT2
      binding sites density. Four parameters of the electroencephalogram (EEG) were
      used to characterize the HVS activity: the square root-transformed EEG peak power
      in the alpha band, the frequency corresponding to this peak (both measured from
      the EEG power spectra using the fast Fourier transform), the HVS mean duration,
      and the HVS incidence (both measured from the EEG records). The EEG parameters
      were analyzed after i.p. administration of three 5-HT2 receptor antagonists:
      ketanserin, ritanserin and cyproheptadine. In young rats, the three drugs
      increased the alpha power, but did not change the alpha peak-corresponding
      frequency. Ketanserin and ritanserin did not change the HVS mean duration and HVS
      incidence, while cyproheptadine increased both these parameters in young rats. In
      middle-aged and old untreated rats, the HVS activity was significantly increased.
      The three 5-HT2 antagonists did not change the HVS activity in aged rats, which
      could be due to age-related suppression of the 5-HT2 receptor functions.

PMID- 9554953
TI  - Angular dependence of electron paramagnetic resonances of an azide-NO complex of
      cytochrome c oxidase: orientation of the haem-copper axis in cytochrome aa3 from
      ox heart.
AB  - The orientation dependence of the EPR signals arising from the azide-nitric oxide
      complex of cytochrome oxidase was investigated using oriented multilayers of
      mitochondrial membranes from ox heart. Variations in line shape of the DeltaMS=1
      signal of the triplet state were apparent, whilst the DeltaMS=2 transitions
      between g=4.7 and 3.9 varied in intensity as the angle of the applied magnetic
      field was varied. These half-field signals were maximal with the field parallel
      to the membrane plane. A model of the bi-liganded azide-nitric oxide complex has
      been constructed, in which the nitric oxide is bound to the high-spin haem in a
      bent configuration, with the Fe-N=O plane at 60-90 degrees to the membrane plane
      and the azide bound to the copper, distal from the haem. In addition, angular
      variations of the signals at g'=11 and g' around 3.5, derived from an integer
      spin complex, were also observed.

PMID- 9554954
TI  - Hypoxia-tolerant neonatal CA1 neurons: relationship of survival to evoked
      glutamate release and glutamate receptor-mediated calcium changes in hippocampal
      slices.
AB  - Neurons in the neonatal mammalian brain survive greater degrees of hypoxic stress
      than those in the mature brain. To investigate how developmental changes in
      glutamate receptor-mediated neurotoxicity contribute to this difference, we
      measured hypoxia-evoked glutamate release, glutamate receptor contribution to
      hypoxia-evoked intracellular calcium changes, and survival of hypoxia-/ischemia
      sensitive CA1 neurons in rat hippocampus. Glutamate release was measured by a
      fluorescence assay, calcium changes in CA1 neurons with fura-2, and cell
      viability using Nissl and fluorescence staining with calcein-AM/ethidium
      homodimer, all in 300-micron thick hippocampal slices from 3-30 post-natal day
      (PND) rats. Glutamate released from PND 3-7 slices during hypoxia (PO2 = 5 mmHg)
      was only one third that of PND 18-22 slices. In PND 3-7 slices, survival of CA1
      neurons after 5 min of hypoxia and 6 h of recovery was significantly greater than
      in PND 18-22 slices (viability indices 0.60 and 0.28, respectively, (p < 0.05).
      Five min of anoxia significantly altered Nissl staining pattern and morphology of
      CA1 neurons in PND 18-22 but not PND 3-7 slices. Hypoxia (PO2 = 5 mm Hg) caused
      three to five times greater increases in [Ca2+]i in PND 18-22 slices than in PND
      3-7 slices (p < 0.001). During re-oxygenation, [Ca2+]i returned to baseline in
      PND 3-7 slices, but remained elevated in PND 18-22 slices. Glutamate receptor
      mediated calcium changes in CA1 during hypoxia were 33% and 62% of the total
      calcium change in PND 3-7 and PND 18-22 CA1, respectively. We conclude that
      survival of CA1 neurons in PND 3-7 slices following hypoxic stress is associated
      with smaller increases and enhanced recovery of [Ca2+]i, less accumulation of
      glutamate, and less glutamate receptor-mediated calcium influx than in PND 18-22
      slices.

PMID- 9554955
TI  - Age-related changes in auditory spatial properties of the guinea pig superior
      colliculus.
AB  - The map of auditory space located in the deep layers of the guinea pig superior
      colliculus (SC) is a complex computational representation of the auditory azimuth
      surrounding the animal. The map undergoes a protracted developmental profile
      during the first postnatal month and remains plastic until well into adulthood.
      However, there are no data concerning the state of the collicular auditory space
      map in much older animals. Multi-unit responses to broadband noise stimuli
      presented around the azimuthal plane under anechoic conditions were recorded from
      the deep SC of guinea pigs of a variety of ages, up to 44 months. The data
      obtained show that the map remains stable up to the age of approximately 36
      months. However, after this age, the map shows rapid deterioration and at 42
      months, multi-unit responses did not show features consistent with a normal map.
      It appears that deficits accruing within the central auditory system with
      increasing age, combine to overcome the ability of the mechanisms of plasticity
      responsible for space map maintenance to keep pace with the changes, resulting in
      degraded SC spatial tuning with increasing age.

PMID- 9554956
TI  - The 9-kDa phosphoprotein of photosystem II. Generation and characterisation of
      Chlamydomonas mutants lacking PSII-H and a site-directed mutant lacking the
      phosphorylation site.
AB  - The chloroplast gene psbH encodes a 9-10 kDa thylakoid membrane protein (PSII-H)
      that is associated with photosystem II and is subject to light-dependent
      phosphorylation at a threonine residue located on the stromal side of the
      membrane. The function of PSII-H is not known, neither is it clear what
      regulatory role phosphorylation may play in the control of PSII activity. Using
      particle gun-mediated transformation, we have created chloroplast transformants
      of Chlamydomonas reinhardtii in which the synthesis of PSII-H is prevented by the
      disruption of psbH, or in which the phosphorylatable threonine is replaced by
      alanine through site-directed mutagenesis of the gene. The mutants lacking PSII-H
      have a photosystem II-deficient phenotype, with no detectable functioning PSII
      complex present in whole cells or isolated thylakoid membranes. In contrast, the
      alanine mutant (T3A) grows photoautotrophically, and PSII activity is comparable
      to wild-type cells as determined by various biochemical and biophysical assays.

PMID- 9554957
TI  - Selective loss of hippocampal long-term potentiation, but not depression,
      following fluid percussion injury.
AB  - We investigated the early effects of in vivo fluid percussion injury (FPI) on
      hippocampal synaptic potentials and excitability. In vitro field potential
      recordings and immunocytochemistry were performed in the CA1 region in slices
      from naive, post-FPI, or sham-operated rats. The following electrophysiological
      and morphological parameters were affected following FPI: (1) threshold for
      population spike generation was increased suggesting that post-FPI neurons were
      hypoexcitable; (2) long-term potentiation (LTP) could not be induced in injured
      hippocampi; (3) GFAP and inducible NO synthase (iNOS) immunoreactivity were
      enhanced post-FPI; and (4) following injury, synaptophysin immunoreactivity was
      enhanced in CA1 stratum radiatum. The effects of FPI on synaptic plasticity were
      LTP-specific, since long-term depression (LTD) could be equally induced and
      maintained in post-FPI, sham-operated and control slices. Sham-operated slices
      were characterized by synaptic excitability indistinguishable from naive
      controls, but displayed decreased ability for LTP production and expressed high
      levels of iNOS. We conclude that FPI causes a selective loss of LTP, possibly due
      to a previous potentiation induced by trauma as reflected by the increased
      expression of synaptic proteins. Sham surgical procedures were, however, not
      without effects on long-term potentiation itself; the latter effects appear to be
      mediated by an increased production of NO. Our study demonstrates for the first
      time that hippocampal slices can be used to investigate the correlates of in vivo
      FPI. Furthermore, we describe LTP-specific deficits in post-traumatic brain
      injury, suggesting that FPI can selectively erase one of the two main NMDA
      dependent forms of synaptic plasticity in the hippocampus.

PMID- 9554958
TI  - 2'-Deoxyadenosine selectively kills nonneuronal cells without affecting survival
      and growth of chick dorsal root ganglion neurons.
AB  - Recently, we have demonstrated that adenosine and 2'-deoxyadenosine are toxic to
      embryonic sympathetic neurons and proposed that purine and pyrimidine metabolism
      may play a critical role in the growth and development of sympathetic neurons. To
      extend this hypothesis further, we examined the effects of these nucleosides on
      two other neuronal populations in the chick embryo, sensory dorsal root ganglion
      neurons and parasympathetic ciliary ganglion neurons. Now, we show that 2'
      deoxyadenosine and adenosine have no visible adverse effect on the viability of
      either sensory or parasympathetic neurons. Instead, 2'-deoxyadenosine proved to
      be highly toxic to the nonneuronal cells. The toxic effects of 2'-deoxyadenosine
      were markedly enhanced by inhibition of adenosine deaminase. In contrast,
      adenosine was much less toxic to nonneuronal cells than 2'-deoxyadenosine and its
      effect was not potentiated by inhibition of adenosine deaminase. Priming of
      pyrimidine pools by exogenous uridine and the specific inhibitor of the
      nucleoside transporter, nitrobenzylthioinosine, did not protect nonneuronal cells
      from 2'-deoxyadenosine toxicity. Since phosphorylation of internalized
      nucleosides was a key step in the initiation of toxicity in sympathetic neurons,
      adenosine kinase activity was compared in sensory and sympathetic neuronal
      cultures. The adenosine kinase activity in dorsal root ganglion cultures was only
      20% of that in sympathetic ganglion cultures. Furthermore, inhibition of
      phosphorylation by blocking 2'-deoxyadenosine kinase with iodotubercidin and 5'
      amino-5'-deoxyadenosine had no protective effect against 2'-deoxyadenosine
      toxicity. [3H]-thymidine incorporation was inhibited over 90% by 2'
      deoxyadenosine as early as 6 h following its addition and for up to 4 days,
      suggesting inhibition of proliferation of nonneuronal cells by 2'-deoxyadenosine.
      The nucleoside was also able to wipe out already well established nonneuronal
      cells, leaving behind an enriched population of sensory neurons. The selective
      vulnerability of nonneuronal cells to 2'-deoxyadenosine offers a convenient and
      effective tool for removing nonneuronal cells from neuronal cultures as well as
      providing a new model for studying the mechanisms of nucleoside toxicity.

PMID- 9554959
TI  - Early patterning of the rat cerebral wall for regional organization of a neuronal
      population expressing latexin.
AB  - The exact timing of regional patterning in the developing cerebral cortex and
      other telencephalic structures remains to be elucidated. In the present study, we
      addressed this issue by comparing the distribution and density of neuronal
      population expressing latexin in the adult rat telencephalon, with the regional
      pattern in the fetal cerebral wall as to the potential to generate latexin
      expressing neurons. Immunohistochemical analyses on adult animals have shown that
      latexin-expressing neurons are restricted to a lateral cortical field, within
      which they are most abundant at the middle level, decreasing in number rostrally
      and caudally. Substantial numbers of latexin-immunopositive neurons were recorded
      in the claustrum and endopiriform nuclei, both of which are located from rostral
      to middle level in the lateral telencephalon. By examining the number and density
      of latexin-immunopositive neurons in organotypic slice cultures from various
      portions of the developing rat cerebral wall, it has been shown that the regional
      pattern within the early cerebral wall as to the potential to generate latexin
      expressing neurons matches well the distribution and density of latexin
      expressing neurons in the adult telencephalon. Thus, in cultures derived from
      either embryonic day 13 or 16 fetuses, latexin-immunopositive neurons appeared
      most prominently in those from rostral-to-middle portions of the lateral cerebral
      wall, decreasing in number rostrally and caudally. In cultures from the dorsal
      cerebral wall, the number was generally very low. In light of our previous
      finding that most prospective latexin-expressing neurons are still dividing at
      embryonic day 13, it can be concluded that some kind of pattern formation event
      occurs within the early cerebral wall even prior to the genesis of the
      postmitotic neurons that would be later allocated in a region-specific manner.

PMID- 9554960
TI  - Isolation of mutants of the Arabidopsis thaliana alternative oxidase
      (ubiquinol:oxygen oxidoreductase) resistant to salicylhydroxamic acid.
AB  - The plant-type ubiquinol:oxygen oxidoreductase, commonly called the alternative
      oxidase, is a respiratory enzyme thought to contain non-heme iron at its active
      site. To explore the structure of the enzyme by identifying amino acids involved
      in inhibitor-binding, a library of random mutants of the Arabidopsis thaliana
      alternative oxidase was constructed using error-prone polymerase chain reaction
      and expressed in the heme-deficient Escherichia coli SASX41B. Selection for
      resistance to salicylhydroxamic acid (SHAM) resulted in the recovery of four
      mutations. Three of these, F215L, M219I, and M219V, confer a small, but
      measurable resistance to SHAM of between 1.4- and 1.7-fold relative to the wild
      type alternative oxidase. These changes are located in a putative amphipathic
      helix following the second transmembrane helix. The fourth mutation, G303E, is
      found three residues from the C-terminus of the protein, and results in 4. 6-fold
      resistance to SHAM. None of the mutations have any effect on the sensitivity of
      the alternative oxidase to propyl gallate. The identification of distant residues
      involved in SHAM resistance suggests that the poorly conserved C-terminal region
      is in spatial proximity to the amphipathic helix, and thus located in the
      vicinity of the iron-binding motif.

PMID- 9554961
TI  - Development of muscle afferents in the spinal cord of the tammar wallaby.
AB  - The development of muscle afferents in the tammar wallaby was examined to address
      whether proprioceptive input contributes to the marked asymmetry of the fore and
      hindlimb movement. Anatomical tracing with biocytin showed that the muscle
      afferents had reached the brachial motor horn by postnatal day (P1), but were
      less advanced in the lumbar region. Labelled cells lying outside the motor horn,
      presumably filled via gap junctions, were evident in the neonatal lumbar cord. By
      the 4th postnatal week, the afferent innervation of both brachial and lumbar
      cords became similar. Afferent discharges from stretching the biceps muscle could
      be recorded at birth, but not until P4 from the hindlimb gastrocnemius muscle.
      The discharges were predominantly phasic until P35 when tonic activity could also
      be recorded. Short latency spinal reflex responses superimposed upon a longer
      lasting potential were present in the brachial cord at birth, appearing in the
      lumbar cord at P4. By the 3rd postnatal week, spinal reflex became comparable in
      both segmental levels. The time course of muscle afferent development was
      compared to the progression of natural cell death in the lumbar cord.
      Sensorimotor connections were established towards the end of the rapid phase cell
      death as observed in other vertebrates.

PMID- 9554962
TI  - Single and repeated episodes of ethanol withdrawal increase adenosine A1, but not
      A2A, receptor density in mouse brain.
AB  - A history of multiple ethanol withdrawal experiences has been shown to exacerbate
      the severity of future withdrawal episodes, and this sensitization of the
      withdrawal response has been hypothesized to represent a 'kindling' phenomenon.
      Since adenosine functions as an inhibitory modulator of seizure activity and may
      interact with ethanol to influence neuronal excitability, the present study was
      conducted to examine the effects of single and repeated episodes of ethanol
      withdrawal on adenosine A1 and A2A receptors in adult C3H/He mice. Mice were
      chronically exposed to ethanol vapor in inhalation chambers and tested for
      withdrawal seizures following multiple withdrawal (MW) experience (four cycles of
      16 h ethanol intoxication interrupted by 8 h periods of abstinence), single
      withdrawal experience following 16 h (SW) or 64 h (CE) continuous ethanol
      intoxication, or no ethanol exposure (controls). Separate groups of mice from
      each withdrawal condition were used to generate pooled cortical and striatal
      tissue for ligand saturation experiments using [3H]cyclohexyladenosine to label
      A1 receptors and [3H]CGS 21680 to label A2A receptors. Results indicated that
      withdrawal seizures were significantly more severe in mice with multiple
      withdrawal experience in comparison to animals that experienced only a single
      withdrawal episode, even when total amount of ethanol exposure was equated among
      groups. The density of A1 receptors in cerebral cortex was significantly
      increased over controls 8 h following final ethanol withdrawal by approximately
      35% in SW and CE groups, with the largest increase observed in the MW group
      (56%). Withdrawal treatment groups did not differ in cortical A1 binding sites
      immediately upon withdrawal from ethanol, and no significant differences in
      binding of [3H]CGS 21680 to striatal A2A receptors were observed following
      ethanol withdrawal. Ethanol exposure and withdrawal did not significantly alter
      ligand affinity for either adenosine receptor. These results indicate that
      adenosine A1 receptors are selectively upregulated during ethanol withdrawal and
      that the degree of upregulation may be enhanced following multiple withdrawal
      episodes. Further, these observations suggest that the upregulation of brain A1
      receptors during ethanol withdrawal may represent a compensatory inhibitory
      response to increased seizure severity associated with repeated episodes of
      ethanol withdrawal.

PMID- 9554963
TI  - Three classes of GABA-like immunoreactive neurons in the mushroom body of the
      cockroach.
AB  - The mushroom body (MB) is a higher center of the insect brain and is critical to
      some forms of associative memory. Each MB consists of calyces connected to alpha
      and beta lobes via pedunculus. In the calyces, input neurons make synaptic
      connections with intrinsic neurons. In the pedunculus and lobes, intrinsic
      neurons make synaptic connections with output neurons. Here, the distribution of
      gamma-aminobutyric acid (GABA)-like immunoreactivity in the MB of the cockroach
      Periplaneta americana was investigated, using an antiserum against a GABA-protein
      conjugate, to elucidate inhibitory pathways of the MB. We report that three
      classes of extrinsic neurons of the MB exhibit GABA-like immunoreactivity. The
      first is four large neurons which arborize in a diffuse neuropil surrounding the
      alpha lobe and project into whole areas of the calyces. Their cell bodies are 30
      50 micron in diameter, among the largest in the brain. The second group is 7-9
      neurons ascending from the circumesophageal connective and projecting into the
      calyces, which probably represent inhibitory input neurons. The third group is
      ca. 40 neurons with dendritic arborizations in the junction between the
      pedunculus and the lobes, which probably represent inhibitory output neurons.

PMID- 9554964
TI  - Permeability of the blood-brain barrier to neurotrophins.
AB  - To evaluate the feasibility of applying blood-borne neurotrophins to promote
      normal function of the central nervous system (CNS) and to rescue neuronal
      degeneration, we characterized the permeability of the blood-brain barrier (BBB)
      to neurotrophins. We report here that some members of the neurotrophin family
      (NGF, betaNGF, NT3, and NT5) can cross the BBB of mice in vivo to arrive at the
      brain parenchyma. BBB permeability differed among individual neurotrophins in
      that NGF had the fastest influx rate (Ki) and NT3 the slowest, and that the entry
      rate of NGF was twice that of its smaller bioactive subunit betaNGF. BBB
      permeability also differed at various CNS regions in that the cervical spinal
      cord had the greatest rate of influx, whereas brain had the lowest. Saturability
      of influx was suggested by self-inhibition studies for NT3 in vivo, and for NGF
      in an in situ brain perfusion system, indicating the presence of saturable
      transport systems. The results suggest that peripheral administration of
      neurotrophins could have therapeutic effects within the CNS.

PMID- 9554965
TI  - Xanthine oxidase-derived superoxide causes reoxygenation injury of ischemic
      cerebral endothelial cells.
AB  - Oxygen free radicals, generated by cerebral ischemia, have been widely implicated
      in the damage of vascular endothelium. Endothelial cells have been proposed as a
      significant source of oxygen free radicals. In the present study, we developed an
      anoxia-reoxygenation (AX/RO) model using pure cultures of cerebral endothelial
      cells (CECs) isolated from piglet cortex to measure CEC oxygen free radical
      production and determine its role in AX/RO-induced CEC injury. CEC injury, as
      measured by lactate dehydrogenase efflux into the culture medium, increased
      progressively with the duration of anoxic exposure, becoming significant after 10
      h. Reoxygenation significantly increased CEC anoxic injury in a time-dependent
      manner. A 55% increase in oxygen free radical production, determined by
      fluorescence detection of dihydroethidium oxidation, was measured at the end of 4
      h reoxygenation in CECs subjected to AX/RO conditions that killed 40% of the
      cells. Blockade of oxygen free radical production with superoxide dismutase (SOD;
      250 and 1000 U/ml) or oxypurinol (50 and 200 microM), a potent xanthine oxidase
      inhibitor, reduced this injury by 32-36% and 30-39%, respectively. Results from
      our in vitro model indicate that CECs produce significant amounts of oxygen free
      radicals following ischemia, primarily from the xanthine oxidase pathway. These
      radicals ultimately have a cytotoxic effect on the very cells that produced them.
      Thus, reductions in oxygen free radical-mediated vascular injury may contribute
      to improvements in neurophysiologic outcome following treatment with oxygen free
      radical inhibitors and scavengers.

PMID- 9554966
TI  - Effects of tetrodotoxin treatment in LGN on neuromodulatory receptor expression
      in developing visual cortex.
AB  - The expression and distribution patterns of transmitter receptors change
      dramatically during pre- and post-natal development of the visual cortex, but the
      factors that control these processes are largely unknown. We have tested the
      hypothesis that input activity from the lateral geniculate nucleus (LGN), one
      major input source to visual cortex, may contribute to the processes underlying
      transmitter receptor redistributions in the visual cortex during development. We
      found that a short period of tetrodotoxin (TTX) treatment in LGN retarded the
      developmental expression and age-dependent reorganization of neuromodulatory
      receptors, including muscarinic, serotonergic and adrenergic receptors, in kitten
      primary visual cortex. The visual cortices ipsilateral to the TTX infusion site
      displayed a 'younger' receptor pattern than that of their contralateral control
      counterparts in the same animals. The results suggest that active input from LGN
      regulates the expression profile of a broad range of receptors in the developing
      visual cortex.

PMID- 9554967
TI  - Altered distribution of Galphah/type 2 transglutaminase following catecholamine
      deprivation is associated with depression of adrenoreceptor signal transduction
      in cultured ventricular zone germinal cells.
AB  - Type 2 transglutaminase (Tg), which catalyzes the covalent cross-linking of
      cytoplasmic proteins during apoptosis, also functions as the alpha subunit of a
      heterodimeric G-protein (Gh) which can activate phospholipase C-delta1 during the
      signal transduction pathway linked to alpha1-adrenoreceptors. Continued
      stimulation of rat forebrain ventricular zone (VZ) germinal cells with the alpha1
      agonist phenylephrine during development in vitro suppresses apoptosis and
      promotes DNA synthesis [Pabbathi et al., Brain Res., 760, 1997, 22-33].
      Immunocytochemistry with a monoclonal antibody to Galphah/Tg reveals that alpha1
      agonist deprivation during culture of VZ cells in the presence of a protein
      synthesis inhibitor results after 20 h in a loss of peripheral distribution of
      the protein and an increase in the reaction product of Tg in the cytoplasm of
      cells undergoing apoptosis. Using photoaffinity labelling, we observed reduced
      GTP binding to Galphah/Tg in phenylephrine-deprived cultures. Formation of
      inositol triphosphate (IP3) and intracellular Ca2+ transients occurred in the
      presence of phenylephrine. In cultures grown in phenylephrine-deprived conditions
      in the presence of protein synthesis inhibitor, both the IP3 response and the
      amplitude and duration of Ca2+ transients were reduced. These results show that
      loss of signal transduction coincides with the onset of transglutaminase activity
      in VZ cells during a period when cell survival is reduced following withdrawal of
      alpha1-agonist, and support the hypothesis that Tg/Galphah could be implicated in
      both signal transduction and programmed cell death.

PMID- 9554968
TI  - Growth factors improve immediate survival of embryonic dopamine neurons after
      transplantation into rats.
AB  - Embryonic dopamine neurons survive poorly after transplant into models of
      Parkinson's disease, possibly due to programmed cell death (apoptosis). Apoptosis
      in cultured dopamine neurons can be reduced by growth factors such as glial cell
      line-derived neurotrophic factor (GDNF) or a combination of insulin-like growth
      factor-I (IGF-I) and basic fibroblast growth factor (bFGF). To improve the
      survival of dopamine neurons in grafts, strands of E15 rat ventral mesencephalon
      were pretreated with a combination of GDNF, IGF-I, and bFGF and then transplanted
      into 6-hydroxydopamine-lesioned rats. In control animals, only 32% of dopamine
      neuron profiles survived the first 24 h after transplant. Growth factor
      pretreatment increased survival to 49% on day 1. Growth factors reduced the
      apoptotic rate of transplanted cells, just as they had in the previous in vitro
      experiments. Apoptotic nuclear morphology was observed in the transplanted
      dopamine neurons. We conclude that the majority of transplanted dopamine neurons
      die in grafts within the first 24 h after transplant, most likely by an apoptotic
      mechanism. Prevention of apoptosis with anti-apoptotic agents may improve the
      viability of dopamine neurons grafted for Parkinson's disease.

PMID- 9554969
TI  - Ontogeny of calretinin expression in rat dorsal root ganglia.
AB  - The relationship between the expression of calretinin and the maturation level of
      peripheral sensory neurons was investigated by means of immunohistochemistry and
      immunoblot analysis. Our immunohistochemical results show that calretinin is
      expressed during two different developmental phases in rat dorsal root ganglia.
      The early phase lasts between embryonic days 11 and 14, when calretinin is
      detectable in the majority (75%) of the cells. A second phase starts at embryonic
      day 17 and lasts throughout the whole postnatal life, when calretinin is
      expressed only in a small proportion of the neurons (less than 8%). Between these
      two periods no calretinin is found in the ganglia. These changes in calretinin
      expression during embryonic development were confirmed by Western blot analysis.
      The early expression of calretinin in dorsal root ganglion cells suggests that
      calretinin may act as a calcium regulator until neurotrophins take over the
      precise tuning of intracellular calcium concentration.

PMID- 9554970
TI  - The effect of MK-801 and of brain-derived polypeptides on the development of
      ischemic lesion induced by photothrombotic occlusion of the distal middle
      cerebral artery in rats.
AB  - The effect of neuroprotective drugs on the early and late electrophysiological
      manifestations of photothrombotic occlusion of distal branches of middle cerebral
      artery was studied in rats treated with MK-801 and Cerebrolysin (CL). DC
      potentials were recorded from the irradiated cortex (ischemic core), from the
      adjacent penumbra zone and from remote intact cortex. Irradiation elicited after
      a few minutes of spontaneous spreading depression (SD) waves followed during 10
      15 min by focal ischemic depolarization (FID) developing in the irradiated cortex
      and spreading into the perifocal areas. While the core FID amplitude reached
      about 30 mV and decayed during subsequent 2 h to 10-13 mV, FID in the penumbra
      zone was broken by periods of partial repolarization and returned during 30-90
      min almost to baseline. At the same time, generation of spontaneous SD waves
      almost stopped. MK-801 (0.5 mg/kg, i.p., 45 min after ischemia) blocked SD waves,
      but did not shorten penumbra FID, the decay of which was slowed down to the rate
      found in the ischemic core. CL treatment (2.5 ml/kg, i.p. , 1 h after ischemia)
      did not influence FID in the acute phase of the experiment, but its 10-day
      administration facilitated post-ischemic recovery indicated by higher amplitude
      of evoked SD waves penetrating into the former penumbra zone. Morphological
      examination showed that the volume of total and partial necrosis was increased in
      the MK-801 group and marginally reduced in the CL group. It is suggested that the
      absence of the SD-induced hyperperfusion episodes in MK-801-treated rats may
      accelerate perifocal thrombotization in this model of focal ischemia.

PMID- 9554971
TI  - Regulation of G protein-mediated adenylyl cyclase in striatum and cortex of
      opiate-dependent and opiate withdrawing mice.
AB  - Previous research has demonstrated that acute and chronic opiate treatment alters
      receptor- and postreceptor-mediated adenylyl cyclase activity. This study
      examined the regulation of G protein- and forskolin-mediated adenylyl cyclase
      activity in mouse striatum and cortex after short- and long-term opiate exposure.
      To directly measure adenylyl cyclase enzymatic activity, assays were done in the
      presence of catalytic site activator forskolin. To measure G protein-mediated
      adenylyl cyclase activity, assays were performed in the presence of non
      hydrolyzable guanosine 5'-triphosphate (GTP) analogue, 5'-guanylyl
      imidodiphosphate. Short-term in vitro morphine exposure produced reductions in
      forskolin-stimulated adenylyl cyclase activity in striatal and cortical tissues.
      Long-term morphine treatment in mice was performed via morphine- or placebo
      pellet implantation for 72 h; this treatment has been shown to produce opiate
      dependence and withdrawal. In both opiate-dependent and opiate withdrawing mice
      (1 h post-naloxone induction), there were significant increases in G protein
      mediated adenylyl cyclase activity in the striatum (vs. controls). In opiate
      dependent mice, there was an decrease in G protein-mediated adenylyl cyclase
      activity in cortex. In opiate-dependent mice, there were no changes in forskolin
      stimulated adenylyl cyclase in the striatum or cortex. Increases in striatal G
      protein-mediated adenylyl cyclase could represent a compensatory adaptation that
      opposes the persistent inhibition of adenylyl cyclase by chronic opiate treatment
      contributing to the expression of opiate dependence and withdrawal.

PMID- 9554972
TI  - Ontogeny of human brain dopamine receptors. I. Differential expression of [3H]
      SCH23390 and [3H]-YM09151-2 specific binding.
AB  - Dopamine receptor expression in human fetal forebrain (between 6 and 20 weeks of
      gestation) was measured using tissue-slice receptor autoradiography with the D1
      like and D2-like antagonists [3H]-SCH23390 and [3H]-YM09151-2, respectively.
      Tissue sections were assayed in saturation studies and examined for age- and sex
      related changes in Bmax. We made the following observations: (1) the ages at
      which D1- and D2-like receptors were first expressed in whole forebrain sections
      could be reliably identified but were not significantly different from one
      another (gestational age 65 days for D1- vs. 72 days for D2-like receptors); (2)
      age-related increases in both D1- and D2-like receptors were demonstrated in
      forebrain and, from the middle of the first to the middle of the second
      trimester, the Bmax for each ligand increased by an order of magnitude after the
      onset of the specific binding site's expression; (3) age-related increases in D1
      like receptors, but not D2-like receptors, could be demonstrated in cortex; and,
      (4) in one case of trisomy 18, the Bmax for [3H]-SCH23390 was significantly
      elevated above the 95% confidence interval when compared to an age-regressed
      normal sample. Although D2-like receptor density significantly increased with age
      in forebrain, age-regressed changes in D2-like receptor expression in cortex and
      striatum did not reach statistical significance. Likewise, a comparison of the
      mean Bmax's by sex for both ligands in midgestational striatum failed to reach
      significance. These data corroborate the findings of other investigators who have
      delineated the ontogeny of dopaminergic systems in other animal species. The
      regional differences in the expression of dopamine receptor families may be
      relevant to the role which dopamine may play during normal gestational brain
      development. Moreover, significant deviations in dopamine receptor expression
      during gestation (as seen in this one case of trisomy 18) may signify underlying
      pathological processes that ultimately are manifested by abnormal psychological
      development and/or cognitive functioning.

PMID- 9554973
TI  - Dopaminergic agonists administered into the nucleus accumbens: effects on
      extracellular glutamate and on locomotor activity.
AB  - The hypothesis to be tested was that increased dopaminergic transmission induced
      by amphetamine in the nucleus accumbens results in increased glutamatergic
      neurotransmission in this brain area and that the increase in level of this
      neurotransmitter contributes to behavioral effects of psychostimulant drugs.
      Amphetamine (1 mg/kg, i. p.) increased the amount of extracellular glutamate in
      the accumbens, as measured by in vivo dialysis, and stimulated locomotor
      activity. Amphetamine (10 mM) infused into the accumbens by reverse dialysis
      through the probe produced a similar stimulation of locomotor activity as
      systemic amphetamine but a greater increase in extracellular glutamate levels.
      Both of these responses to amphetamine were attenuated by either the selective D1
      antagonist SCH23390 or the selective D2 antagonist eticlopride. The combination
      of a D1 and D2 agonist, SKF38393 (20 mM) and quinpirole (50 mM), administered
      into the accumbens by reverse dialysis also increased extracellular glutamate and
      stimulated locomotor activity. Administration of a glutamate uptake inhibitor,
      threo-beta-hydroxy-aspartate (50 mM), increased extracellular glutamate but did
      not stimulate locomotor activity. Systemic administration of caffeine (15 mg/kg,
      i.p.) increased locomotor activity but did not increase extracellular levels of
      glutamate. These data suggest that activation of dopaminergic receptors in the
      nucleus accumbens results in stimulation of locomotor activity and in activation
      of glutamatergic transmission in this brain region. However, an increase in
      glutamate levels in the nucleus accumbens is neither sufficient nor necessary to
      produce a stimulation of locomotor activity.

PMID- 9554974
TI  - Inhibitory neuronal activity can compensate for adverse effects of beta-amyloid
      in hippocampal neurons.
AB  - One of the most prominent effects of Alzheimer disease is the disruption of
      finely tuned neuronal circuitry of discrete brain regions associated with
      learning and memory. Results from the present study support a role for the
      intrinsic inhibitory component of neuronal circuitry in determining the magnitude
      of beta-amyloid peptide induced cell death in the highly vulnerable pyramidal
      neurons of the hippocampus. Previous efforts have mostly focused on direct
      effects on excitatory neurons. By contrast, less emphasis has been placed on
      addressing a role for the intrinsic inhibitory component of cell-cell
      interactions of neuronal networks in response to Abeta. The present study
      provides evidence demonstrating that blockage of the intrinsic inhibitory
      component between Abeta exposed neurons leads to destabilization of calcium
      homeostasis and exacerbated neuronal death compared to Abeta treated cultures.
      Neuronal electrical activity was first silenced by exposing cultures to
      tetrodotoxin (TTX; 100 nM) plus Abeta, followed by survival counts. Cell death,
      unexpectedly, did not significantly differ from Abeta-exposed neurons. The
      intrinsic inhibition in Abeta-exposed cultures was then pharmacologically removed
      with picrotoxin (40 microM) or bicuculline (25 microM) resulting in significantly
      greater death than Abeta-exposed neurons alone. From these observations, it is
      proposed that intrinsic functional inhibition in hippocampal circuits can reduce
      adverse effects of Abeta on the excitatory component. By considering not just the
      excitatory component of electrical activity, but the intrinsic balance between
      excitation and inhibition, new strategies for the treatment of Alzheimer disease
      may emerge.

PMID- 9554976
TI  - Mecamylamine selectively blocks nicotinic receptors on vasomotor sympathetic C
      neurons.
AB  - Mecamylamine differentially blocked fast nicotinic transmission in two functional
      subsets of sympathetic neurons within lumbar paravertebral ganglia of the
      bullfrog. EC50s for inhibition of postsynaptic compound action potentials were
      27.3+/-2.5 microM in the secretomotor B system and 5.7+/-0.7 microM in the
      vasomotor C system. This 5.2:1 selectivity is 2.6 times greater than observed
      previously with d-tubocurarine, a nonselective blocker of nicotinic receptors,
      and it indicates that mecamylamine preferentially interacts with nicotinic
      receptors on sympathetic C neurons. We tested this by analyzing the effect of
      mecamylamine upon synaptic currents. In both cell types, the drug produced a
      qualitatively similar picture of open-channel blockade. It reduced EPSC
      amplitude, speeded EPSC decay, and became more effective with membrane
      hyperpolarization and repetitive activity. Despite these similarities, 8 microM
      mecamylamine reduced EPSC amplitude to a greater extent in C neurons, and the
      rate constant for drug binding to open channels was 4.4 times greater in B cells,
      irrespective of membrane potential. This implies that the unblocking rate for
      mecamylamine is much slower in C cells than B cells, and it shows that the drug
      recognizes a structural difference between nicotinic receptors on these two
      populations of sympathetic neurons.

PMID- 9554975
TI  - Elevation of cyclic AMP by iloprost and prostaglandin E1 increases cholesterol
      efflux and the binding capacity for high-density lipoproteins in human
      fibroblasts.
AB  - Elevation of cAMP concurrently enhances cholesterol efflux and binding of HDL3 in
      human skin fibroblasts. These effects were observed regardless of the route by
      which cAMP levels were increased. Cholesterol efflux and HDL3 binding were
      stimulated by the cAMP analogue CPT-cAMP, the adenylate cyclase activator
      forskolin, and by iloprost and prostaglandin E1 (PGE1) (which elevate cAMP via
      receptor-mediated processes). Dideoxyforskolin and PGF2alpha, which do not
      elevate cAMP, altered neither cholesterol efflux nor binding of HDL3. Inhibition
      of protein kinase A with H89 abolished the stimulatory effects of CPT-cAMP and
      iloprost, suggesting protein kinase A involvement in enhancing cholesterol efflux
      and HDL3 binding. Enhancement of HDL3 binding by iloprost was due to increased
      maximal capacity of the cells to bind HDL3, i.e., a greater number of HDL3
      binding sites. A positive correlation was demonstrated between changes in HDL3
      binding and changes in [3H]cholesterol efflux. The data are compatible with a
      model in which cholesterol efflux is partially dependent upon HDL binding to the
      cells. A short exposure to iloprost was sufficient to stimulate cAMP synthesis,
      triggering a chain of events leading to increased HDL3 binding and
      [3H]cholesterol efflux 20-24 h later. We conclude that both cholesterol efflux
      and the maximal capacity for HDL3 binding are enhanced by elevation of cellular
      cAMP. Cyclic AMP-elevating prostanoids could initiate these responses in vivo.

PMID- 9554977
TI  - The effects of fetal adrenalectomy at 110 days gestational age on AVP and CRH
      mRNA expression in the hypothalamic paraventricular nucleus of the ovine fetus.
AB  - AVP and CRH produced in the parvocellular neurons of the paraventricular nucleus
      (PVN) have both been implicated in the regulation of anterior pituitary ACTH
      synthesis and secretion. In sheep, fetal ACTH secretion increases around 120 days
      gestational age (dGA). Little is known about adrenal regulation of AVP and CRH
      immediately prior to this critical period. We investigated the effects of
      adrenalectomy and subsequent cortisol (F) administration on PVN AVP and CRH mRNA
      in the fetal sheep PVN at 109-125 dGA. At 109-113 dGA, fetal sheep adrenals were
      removed (ADX)(n = 8); or sham surgery performed (CONT)(n = 4). From day 6 post
      ADX, maternal plasma cortisol and fetal plasma ACTH and cortisol levels were
      determined daily by radioimmunoassays. From day 7 post ADX, cortisol (4
      micrograms/min) was continuously infused intravenously to four ADX fetuses (ADX +
      F). Fetal hypothalami were collected at 123-125 dGA, and studied by in-situ
      hybridization and quantitative autoradiography for AVP and CRH mRNA. Plasma
      cortisol levels remained low in CONT and ADX fetuses (< 4.9 ng/ml), while during
      cortisol infusion to ADX + F fetuses, plasma F increased to 16.4 +/- 2.2 and 22.3
      +/- 3.2 ng/ml (mean +/- S.E.M.) on day 10 and 13, respectively. Plasma ACTH
      levels increased significantly in ADX compared with CONT fetuses. This ACTH
      increase was completely suppressed in ADX + F fetuses. AVP mRNA abundance in the
      whole PVN was the same in all three groups, however, a separate analysis of AVP
      mRNA abundance in parvocellular and magnocellular regions of the PVN revealed
      that AVP mRNA in the parvocellular PVN showed a significant increase in ADX and
      suppression in ADX + F fetuses when compared to CONT. AVP mRNA in the
      magnocellular PVN remained unchanged. PVN CRH mRNA expression was augmented in
      ADX and suppressed in ADX + F when compared to CONT fetuses. We conclude that in
      fetal sheep at 109-125 dGA: AVP and CRH mRNA abundance in the parvocellular
      region of the PVN are increased by adrenalectomy and that cortisol inhibits this
      increase.

PMID- 9554978
TI  - Simultaneous microdialysis in brain and blood of the mouse: extracellular and
      intracellular brain colchicine disposition.
AB  - A simultaneous brain and blood microdialysis system was developed to study the
      passage of colchicine through the blood-brain barrier in the mouse. Colchicine
      was administered as a bolus in the jugular vein (1.5 mg kg-1) and its hippocampal
      extracellular fluid (ECF) and blood kinetics were determined over a 4 h period
      using two microdialysis probes, one in the dorsal hippocampus, the other in the
      inferior vena cava. Colchicine rapidly diffused into the hippocampus (maximum
      concentration in the first dialysate sample) and brain and blood concentrations
      declined in parallel, suggesting rapid equilibration between these two
      compartments. However, only 6. 7% of total blood colchicine, 14% of unbound
      colchicine was present in the hippocampus suggesting that the P-glycoprotein
      efflux pump limits colchicine uptake by the brain. We also found, using
      conventional tissue homogenate analysis in parallel, that the concentration of
      colchicine in the hippocampal ECF was 10 times less than that in the
      intracellular space and that the hippocampus colchicine concentration was 2.8
      times higher than that of the rest of the brain. This study shows that the
      simultaneous brain and blood microdialysis can be used to measure the passage of
      colchicine through the blood-brain barrier and to estimate the brain extra- and
      intracellular distribution of colchicine.

PMID- 9554979
TI  - An in vitro model for analysis of oxidative death in primary mouse astrocytes.
AB  - Astrocytes provide a vital protective function in the brain. These cells are also
      vulnerable to oxidative stress, thus their loss of function could contribute to
      neurodegeneration. The goal of this study is to develop a cell culture model to
      study oxidative stress in astrocytes. Enriched astrocytic cultures were generated
      from neonatal mice. tertiary-butyl hydroperoxide (t-bOOH) was used as an
      exogenous peroxide and lactate dehydrogenase (LDH) release as a measure of loss
      of viability. Exposure to t-bOOH resulted in a linear increase in astrocytic
      death reaching 91.2% after 4 h exposure. That cell death was due to oxidative
      injury, was shown by the ability of the antioxidant N,N'-diphenyl-1,4
      phenylenediamine (DPPD) to protect the t-bOOH treated cells. The involvement of
      iron in cell toxicity was demonstrated by the ability of the iron specific
      chelator desferal (DF) to completely prevent t-bOOH induced LDH release. Cells
      treated with a lipid soluble iron compound 3,5, 5-trimethyl (hexanoyl) ferrocene
      (TMH-Ferrocene), were more vulnerable to t-bOOH whereas neither ferrous ammonium
      sulfate (FAS) nor ferric ammonium citrate (FAC) had an effect. The increased
      sensitivity of the cells exposed to TMHF was reversible with the iron chelator
      desferal. Addition of recombinant human heavy chain ferritin or human apo
      transferrin (Tf) did not alter LDH release. Electron microscopic analysis
      indicated astrocytes exposed to t-bOOH exhibited mitochondrial swelling prior to
      cell death (lactate dehydrogenase release). Additional increases in mitochondrial
      swelling were seen when the astrocytes were exposed to the lipophilic iron
      compound TMH-ferrocene and t-bOOH. These studies show that astrocytes are
      exquisitely sensitive to oxidative stress and that their vulnerability is related
      to and enhanced by iron. Decreased mitochondrial function in response to
      oxidative stress may precede cell death.

PMID- 9554980
TI  - The protective role of mild acidic pH shifts on synaptic NMDA current in
      hippocampal slices.
AB  - Glutamate is a major neurotransmitter in the CNS. Its release activates NMDA and
      non-NMDA receptors on the postsynaptic membrane. NMDA receptor activation is
      shown to be important in physiological and pathological events. The modulatory
      sites on the NMDA receptor-channel ionophore complex are important in the
      regulation of the channel's cation conductance. Regulation of the channel by
      proton concentration may be important in the alkalinization that occurs during
      the normal release of glutamate or in the acidification that occurs during
      hypoxia/ischemia. In this study, the selective downregulation of the NMDA channel
      with slight extracellular pH changes and reversibility of this modulation have
      been shown in hippocampal slices. It has also been shown that hippocampal slices
      are more responsive to pH changes than other experimental preparations. The
      downregulation of the NMDA current may represent a native control mechanism.
      Direct and indirect modulation caused by extracellular pH changes on the NMDA
      receptor ionophore complex might be important in the overall response of the
      neuron under pathophysiological changes.

PMID- 9554981
TI  - Potassium chloride inhibits proliferation of cerebellar granule neuron
      progenitors.
AB  - CNS neurogenesis involves a critical transition where neuronal progenitors exit
      the cell cycle and initiate terminal differentiation. Recent experiments have
      suggested that depolarization inhibits DNA synthesis in cortical progenitors.
      Depolarization of proliferating neuronal progenitors may thus activate mechanisms
      that prevent proliferation and allow the initiation of terminal differentiation.
      We present evidence that depolarizing concentrations of KCl (25-50 mM) reduce
      proliferation of developing postnatal cerebellar granule cells in culture. These
      studies show that KCl antagonizes the mitogenic response of granule cells to
      insulin-like growth factor-I (IGF-I) and that this reduction in proliferating
      cells is not the result of a selective cell death. We also examined the
      differentiation of granule cell cultures using Brn-5 expression as an early
      differentiation marker. In vivo Brn-5 expression occurs soon after developing
      granule cells exit the cell cycle and begin their final differentiation. In
      control cultures and cultures treated with high concentrations of KCl Brn-5
      expression increased over 24-48 h of culture. Our results suggest depolarizing
      concentrations of KCl antagonize proliferation of cerebellar granule neuron
      progenitors however allow their continued differentiation.

PMID- 9554982
TI  - A peptide from hog plasma that inhibits human cholesteryl ester transfer protein.
AB  - A peptide that inhibits the human cholesteryl ester transfer protein (CETP) was
      isolated from hog plasma by ultracentrifugation, two sequential column
      chromatographies and electroelution from gels. Molecular weight of the peptide
      was determined to be approximately 3 kDa on the SDS-PAGE. The peptide contained
      28 amino acids with an identical sequence to the amino terminus of hog
      apolipoprotein-CIII except two amino acid residues: -Pro-Glu- at the fifth and
      sixth amino acids from the amino terminus in the isolated peptide, in contrast to
      -Leu-Leu- in hog apo-CIII. A peptide synthesized chemically according to the
      amino acid sequence of the peptide (designated P28) showed approximately the same
      degree of CETP inhibitory activity as the isolated peptide. Synthetic peptides
      with different number of amino acids were also tested for CETP inhibition. Among
      the peptides, the one with 20 amino acid residues (P20) from the amino terminus
      showed the highest inhibitory activity against the CETP. The peptide appeared to
      be associated with the hog high-density lipoproteins (HDL), as determined by
      immunoblot analysis using antibody against P28. The CETP-inhibitory activity of
      the peptide was examined in vivo using diet-induced hypercholesterolemic rabbits.
      When the peptide was injected into the rabbits (7-9 mg/kg body weight),
      approximately 75% CETP activity disappeared from the plasma in 1 h after the
      injection and the effect lasted up to 30 h. The inhibition of CETP in vivo led to
      a concomitant decrease in total plasma cholesterol level up to 30% and an
      increase in the level of HDL-cholesterol up to 32%. The cholesterol
      concentrations in the rabbit plasma gradually recovered to the initial level
      after 48 h.

PMID- 9554983
TI  - Low dose MK-801 protects against iron-induced oxidative changes in a rat model of
      focal epilepsy.
AB  - We have used chemiluminescence measurements to examine the relationship between
      free radical formation and excitotoxicity in a post-traumatic epilepsy model. For
      this purpose, seven days after injecting iron in rat brain cortices, we measured
      luminol- and lucigenin-enhanced chemiluminescence in different brain regions
      (ipsilateral cortex, contralateral cortex, hypothalamus and hippocampus). In all
      brain regions (except contralateral cortices) both luminol- and lucigenin
      enhanced chemiluminescence were increased in iron-injected group compared to
      saline-injected control group. These increases returned to control values in iron
      injected rats pretreated with MK-801. Our results suggest that both free radicals
      and excitatory amino acids play important roles in the development of post
      traumatic epilepsy and that MK-801 has protective effects against iron-induced
      chemiluminescence formation.

PMID- 9554984
TI  - Effects of kappa and delta opioid agonists on activity and thermosensitivity of
      rat hypothalamic neurons.
AB  - Extracellular recordings were made from 161 warm-sensitive, six cold-sensitive
      and 153 temperature-insensitive neurons in slices of the preoptic area/anterior
      hypothalamus (PO/AH) of rats, to investigate the effects of the kappa-receptor
      opioid agonist dynorphin A1-17 and the delta-receptor opioid agonist DPDPE on
      neuronal response characteristics. While 61% of the neurons exhibited kappa
      receptors, delta-receptors were only present in 37% of the neurons. No co
      localization was observed between kappa- and delta-receptors, whereas mu
      receptors could be co-localized with kappa- as well as delta-receptors.
      Antagonistic effects on tonic activity were induced by different concentrations
      of the kappa-agonist dynorphin A1-17. At 0.5 nM, the excitatory effect was
      predominant, while 50% of the neurons were already inhibited at 5 nM and
      inhibition was the major effect at 100 nM. A significant increase in temperature
      sensitivity was observed in warm-sensitive neurons during administration of 0.5
      nM dynorphin A1-17; in contrast, the temperature sensitivity was significantly
      decreased at the high dose of 100 nM. In most of the neurons responding to the
      delta-receptor agonist DPDPE (0.5-100 nM) the firing rate was decreased. The
      temperature sensitivity was only affected in warm-sensitive neurons, and was
      increased in the majority of neurons at 0.5 and 5 nM, but predominantly decreased
      at higher concentrations. The effects of low concentrations of dynorphin A1-17
      and DPDPE were prevented by pre- and co-perfusion of the appropriate antagonists.
      The present results suggest that changes of the temperature sensitivity of warm
      sensitive PO/AH neurons are an important mechanism for the effect of low doses of
      opioids on body temperature.

PMID- 9554986
TI  - The influence of preischemic hyperglycemia on acute changes in brain water ADCw
      following focal ischemia in rats.
AB  - The effect of preischemic hyperglycemia on the acute decline of brain apparent
      diffusion coefficient of water (ADCw) following cerebral ischemia was studied in
      a rat model of middle cerebral artery occlusion (MCAO). ADCw was measured by NMR
      with a newly developed spin-echo line-scan protocol that provides for an ADCw
      calculation every 15 s at a spatial resolution of 3.4 microl/pixel. A remote
      controlled occluding device was used to initiate ischemia from outside the
      magnet, allowing for continuous monitoring of ADCw before, during and after MCAO.
      Preischemic hyperglycemia (25-30 mM) was achieved via i.v. infusion of 50%
      glucose. The decline in ADCw following ischemia was analyzed to obtain three-time
      constants: the time from onset of ischemia to initial significant ADCw decline
      below baseline level (i.e., 20% of maximal decline, T0.20), the time to decline
      by 50% (T0.50), and the time to decline by 95% (T0.95). Mean (+/-S.D.) values for
      T0.20, T0.50, T0.95 were: 39.6+/-7.2, 54. 0+/-7.8, 105.0+/-15.0 s for the
      normoglycemic group (n=7), and 49. 2+/-33.0, 116.4+/-2.4, 351.0+/-189.0 s for the
      hyperglycemic group (n=6), respectively. Hyperglycemia significantly prolongs
      T0.50 and T0.95 but does not affect T0.20. The temporal profiles of ADCw decline
      following ischemia under normo- and hyperglycemia are distinctively different
      from the known time course of membrane depolarization under similar experimental
      conditions, suggesting that mechanisms other than membrane depolarization and
      cell swelling may contribute to changes in ADCw in cerebral ischemia.

PMID- 9554985
TI  - D1-dopamine receptor binding and tyrosine hydroxylase-immunoreactivity in the
      fetal and neonatal hamster suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) of the anterior hypothalamus is the site of an
      endogenous biological clock that regulates mammalian circadian rhythms. Circadian
      rhythms, although endogenously driven, are synchronized or entrained to daily
      environmental cues. Developmentally, the SCN begins to oscillate before birth and
      is entrained to the maternal circadian rhythm by a mechanism that is still
      unclear. Recent evidence in rats and hamsters suggests that a fetal dopaminergic
      system and D1-dopamine receptors may be involved in the process of entraining the
      fetal clock. The present study using [3H]SCH 23390 autoradiography and tyrosine
      hydroxylase (TH) immunocytochemistry determined the developmental time courses of
      the appearance of D1 receptor in, and catecholaminergic input to, the hamster
      SCN. [3H]SCH 23390 binding to D1-dopamine receptors was first detected in the
      fetal SCN on embryonic day (E) 15, the day before birth in this species, and
      persisted through adulthood. The TH immunoreactive fibers were first observed on
      day E15 coursing just ventral to the fetal SCN but TH-immunoreactive cells and
      fibers were not seen within the SCN until postnatal day (P) 5. The presence of D1
      dopamine receptor binding in the fetal hamster SCN is consistent with the role of
      these receptors in entrainment of the fetal circadian pacemaker to maternal cues.
      However, a receptor-transmitter mismatch exists between D1-dopamine receptors and
      TH-immunoreactive fibers in the fetal SCN suggesting that the role of dopamine in
      maternal-fetal entrainment may be as a paracrine or humoral signal.

PMID- 9554987
TI  - Electrophysiological evidence that a subset of midbrain dopamine neurons
      integrate the reward signal induced by electrical stimulation of the posterior
      mesencephalon.
AB  - This study was aimed at determining whether midbrain dopamine (DA) neurons are
      trans-synaptically activated by rewarding electrical stimulation applied near the
      midline in the posterior mesencephalon (PM), and in the affirmative, whether the
      increase in firing was proportional to the rewarding effectiveness of the
      stimulation. Experiments were performed on male Long-Evans rats trained to lever
      press to obtain 400 ms trains of cathodal rectangular pulses. Following the
      training period, curves relating the rates of responding to the stimulation
      frequencies were determined at two current intensities and reward thresholds were
      calculated for each animal. Each animal was then anesthetized with urethane (1.2
      g/kg, i.p.) and firing rate of DA neurons were recorded before, during, and after
      each of 50 trains (1 train/3 s) of stimulation to the PM using stimulation
      parameters that either sustained near threshold responding (rewarding), or failed
      to sustain responding (non-rewarding), in the behavioral tests. A total of 24 DA
      cells were recorded from 13 behaviorally trained animals, and of these, 17 (71%)
      responded to rewarding stimulation by an increase in firing, five (21%) were
      unresponsive and two (8%) were inhibited. In 12 of the 17 cells that were
      activated, the increase in firing was proportional to the rewarding effectiveness
      of the stimulation rather than the total strength of the stimulation. These
      results provide evidence that a subset of midbrain DA neurons are trans
      synaptically activated by rewarding PM stimulation and constitute a second, or
      subsequent, stage of the reward-relevant pathway that integrates the PM reward
      signal.

PMID- 9554988
TI  - The effects of glucose, mannose, fructose and lactate on the preservation of
      neural activity in the hippocampal slices from the guinea pig.
AB  - Using hippocampal slices from guinea pigs, we investigated the effect of
      different concentrations of glucose and replacement of glucose with mannose,
      fructose and lactate on neural activity. As an index of neural activity, the
      population spikes (PS) were recorded in the granule cell layer of the dentate
      gyrus (DG) and the pyramidal cell layer of the CA3 area in the hippocampal
      slices. Lowering the concentration of glucose from 10 mM to 5, 3, 2, 1 and 0 mM
      caused a reduction in the PS amplitude. There were differences in the decay times
      of the PS evoked in these two regions. PS evoked in CA3 region decayed faster
      even at a concentration of 3 mM glucose at which PS in granule cell layer was
      well maintained. The decay time of the PS in the CA3 region in the presence of
      glucose up to a concentration of 3 mM was shorter than that evoked in the DG.
      After the replacement of glucose with mannose, fructose or lactate, the PS
      disappeared within 35 min and there were no significant differences between the
      decay times in the two regions of slices incubated in the same medium. ATP,
      creatine phosphate (CrP) and lactate levels in each slice were determined. To
      investigate whether mannose and fructose could be metabolized or not in the
      tissue slice, anaerobic production of lactate from glucose, mannose and fructose
      were measured during oxygen and glucose deprivation. Under anaerobic conditions
      for 60 min, the levels of high-energy phosphates decreased to 50% of the initial
      level and lactate was produced from glucose, mannose or fructose. However, there
      were significant differences in the rate of lactate production between the DG and
      CA3 areas during application of 3 mM glucose, 10 mM mannose and 10 mM fructose.
      These results indicate that mannose, fructose and lactate can be metabolized and
      are available for maintaining the levels of high-energy phosphates but not for
      neural activity in the tissue slices and that the presence of glucose is
      indispensable for the maintenance of neural activity.

PMID- 9554989
TI  - Maturational changes in cell surface antigen expression in the mouse retina and
      optic pathway.
AB  - The distribution of the cell surface molecules M6 and L1 was studied using the
      immunohistochemistry and in situ hybridization in the developing and adult mouse
      retina and optic nerve. L1 is a cell adhesion molecule while M6 is a cell surface
      molecule homologous to the myelin protein proteolipid protein (PLP/DM20).
      Although both molecules were expressed in retina and optic nerves of embryonic
      and neonatal mice, our studies show that their patterns of postnatal expression
      are quite different. While L1 continues to be expressed in optic axons throughout
      adulthood, expression of M6 on optic axons declines after birth and instead
      becomes strongly expressed on Muller glial endfeet and in the inner plexiform
      layer. The modulation of these molecules after birth could provide clues to
      changing cell-cell interactions occurring in the proximal portion of the optic
      pathway.

PMID- 9554990
TI  - Stearoyl-CoA desaturase mRNA is transcribed from a single gene in the ovine
      genome.
AB  - Clones corresponding to ovine stearoyl-CoA desaturase (SCD) cDNA were isolated
      from an adipose tissue cDNA library. All of these clones represented a single
      mRNA species as judged by restriction fragment and DNA sequence analysis. RNase
      protection analysis demonstrated that this SCD transcript is highly expressed in
      adipose tissue and liver, and in the mammary gland of lactating animals. A lower
      level of expression was detectable in a variety of other tissues including brain.
      Levels of the SCD transcript were decreased in adipose tissue during lactation,
      and this appears to be related to a marked decline in serum insulin and insulin
      responsiveness of the tissue. Southern analysis of ovine and mouse genomic DNA
      demonstrated that the ovine SCD cDNA hybridised in a manner consistent with a
      single gene for SCD in ovine DNA; mouse genomic DNA produced a pattern of
      hybridisation consistent with the previously characterised mouse SCD-1 and SCD-2
      genes. Three ovine cosmids were isolated that comprised the restriction fragments
      predicted by the genomic Southern analysis. The ovine SCD gene was predicted to
      be encompassed within a 23 kbp region that was present in all three cosmids.
      These results demonstrate that SCD is transcribed from a single gene in the ovine
      genome and this gene is insulin-responsive in ovine adipose tissue.

PMID- 9554991
TI  - Apolipoprotein-E deficiency results in an altered stress responsiveness in
      addition to an impaired spatial memory in young mice.
AB  - It has been suggested that Alzheimer's disease (AD) is associated with an altered
      neurotrophic function of apolipoprotein-E (ApoE) and abnormal neuroendocrine
      activities. In the present study we investigated stress responsiveness of ApoE
      deficient mice. Firstly, two sessions of restraint were introduced, 20 min per
      day for two (session 1) and three (session 2) consecutive days. In session 1,
      there was no difference between genotypes in open-field activity in response to
      restraint stress. In session 2, spatial memory was assessed in a Morris Water
      Maze 'Place Learning Set' task immediately following stress. Restraint stress
      caused a significant impairment of spatial memory in wild-type mice. The non
      restraint ApoE-deficient mice showed a severe impairment of spatial memory
      similar to that of the restrained wild-type mice. Restraint stress had no obvious
      effect on spatial memory in ApoE-deficient mice until the third day of testing,
      when there was a decrease in reference memory compared with their non-restraint
      controls. In addition, the first session of restraint stress had an inhibitory
      effect on food intake in wild-type but not ApoE-deficient mice, and a longer
      lasting effect on body weight in the wild-type than ApoE-deficient mice. ApoE
      deficient mice showed a weaker corticosterone response to the initial restraint
      stress and a slower descending rate in serum corticosterone level during a 30-min
      post-stress period than their wild-type controls. However, higher baseline levels
      and stronger corticosterone responses were observed in ApoE-deficient mice than
      in wild-type mice when exposed to repeated restraint stress. The expression of
      ApoE mRNA was upregulated in the hypothalamus in wild-type mice exposed to
      repeated restraint stress. Taken together, these results demonstrate that ApoE
      deficiency causes a memory impairment and an altered stress responsiveness in
      mice.

PMID- 9554992
TI  - CNS cell groups projecting to sympathetic outflow of tail artery: neural circuits
      involved in heat loss in the rat.
AB  - In the rat, approximately 20% of total body heat-loss occurs by sympathetically
      mediated increases in blood flow through an elaborate system of arteriovenous
      anastomoses in the skin of its tail. In this study, the CNS cell groups that
      regulate this sympathetic outflow were identified by the viral transneuronal
      labeling method. Pseudorabies virus was injected into the wall of the ventral
      tail artery in rats that had their cauda equina transected to eliminate the
      somatic innervation of the tail. After 4-7 days survival, the pattern of CNS
      transneuronal labeling was studied. Sympathetic preganglionic neurons in the T11
      L2 (mainly L1) levels of the intermediolateral cell column (IML) were labeled by
      4 days. After 5 days, sympathetic pre-motor neurons (i.e., supraspinal neurons
      that project to the IML) were identified near the ventral medullary surface; some
      of these contained serotonin immunoreactivity. Additional groups of the
      sympathetic premotor areas were labeled by 6 days post-injection, including the
      rostral ventrolateral medulla (C1 adrenergic neurons), rostral ventromedial
      medulla, caudal raphe nuclei (serotonin neurons in the raphe pallidus and magnus
      nuclei), A5 noradrenergic cell group, lateral hypothalamic area and
      paraventricular hypothalamic area (oxytocin-immunoreactive neurons). Seven days
      after the PRV injections, additional cell groups in the telencephalon (viz., bed
      nucleus of the stria terminalis, medial and lateral preoptic areas and medial
      preoptic nucleus), diencephalon (viz., subincertal nucleus, zona incerta as well
      as dorsal, dorsomedial, parafascicular, posterior and ventromedial hypothalamic
      nuclei) and midbrain (viz., periaqueductal gray matter, precommissural nucleus,
      Edinger-Westphal nucleus and ventral tegmental area) were labeled. The discussion
      is focused on the CNS cell groups involved in the control of body temperature and
      fever.

PMID- 9554994
TI  - Kinetic mechanism of glutathione conjugation to leukotriene A4 by leukotriene C4
      synthase.
AB  - The kinetic mechanism for human leukotriene (LT) C4 synthase, a membrane-bound
      glutathione S-transferase, which catalyzes the conjugation of glutathione (GSH)
      to 5,6-oxido-7,9,11, 14-eicosatetraenoic acid (LTA4), to form 5(S)-hydroxy-6(R)-S
      glutathionyl-7,9,trans-11, 14-cis-eicosatetraenoic acid (LTC4) was investigated
      by initial rate kinetic studies in which concentrations of both substrates and
      the reversible dead-end inhibitor, 2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[(5
      phenylpyridin-2-yl)- methoxy]- 4,5-dihydro-1H-thiopyrano[2,3,4-c,d]indol-2
      yl]ethoxy]butanoic acid (L-699,333) were varied. Analysis of the initial
      velocities of LTC4 formation in the absence of the inhibitor using non-linear
      regression fits of various models to the data favoured a random, rapid
      equilibrium mechanism, with strong substrate inhibition by LTA4, over both a
      compulsory ordered mechanism and a ping-pong mechanism. The estimated parameters
      were calculated to be Vmax = 14 +/- 4 microM/min, KLTA4 = 40 +/- 18 microM, KGSH
      = 0.4 +/- 0.2 mM, and a KiLTA4 = 2.3 +/- 1.7 microM for the rapid equilibrium
      random model. Inhibition of enzymatic activity by L-699,333 was found to be
      reversible as assessed by the ability of the enzyme to restore its activity by
      95% upon dilution. L-699,333 was found to be a competitive inhibitor against GSH
      and non-competitive against LTA4. Non-linear least squares regression analysis
      yielded estimated parameters of Km = 0.7 +/- 0.1 mM, Vmax = 2.5 +/- 0.1
      microM/min, and Ki = 0.7 +/- 0.1 microM for GSH at a fixed LTA4 concentration of
      20 microM, and Km = 45 +/- 3 microM, Vmax = 4.9 +/- 0.2 microM/min, and a Ki =
      5.8+/-0.4 microM for LTA4 at a fixed GSH concentration of 2 mM. The rate equation
      for the random equilibrium mechanism accommodates the inhibition patterns
      observed for L-699,333 against both substrates as revealed by kinetic fits of the
      inhibition data to the overall rate equation.

PMID- 9554993
TI  - Neuronal and glial epitopes and transmitter-synthesizing enzymes appear in
      parallel with membrane excitability during neuroblastoma x glioma hybrid
      differentiation.
AB  - The membrane excitability and the presence of neural proteins, including neuronal
      and glial markers and neurotransmitter-synthesizing enzymes, were examined in
      parallel while the NG108-15 cell line was maintained in a serum-free medium.
      Whole-cell recordings in voltage-clamp or current-clamp configurations were used
      to evaluate the membrane excitability, and immunostaining was done with a panel
      of well-characterized antibodies against NSE, NF150, S-100 beta, GFAP, ChAT and
      TH. Culture for 4 to 10 days led to a striking rise in neurite outgrowth,
      electrical excitability and expression of neural proteins in type I neuron-like
      cells, which were of both neuronal and glial character, and expressed both
      cholinergic and adrenergic traits. After about 2 weeks, type II cells which lack
      neurite processes began to emerge. The type II cells proliferated, as revealed by
      BrdU uptake, and gradually overgrew differentiated cell types. They exhibited
      little or no membrane excitability and absence of immunoreactivity for the
      neuronal and glial specific proteins tested. These measurements indicate that the
      presence of these neural proteins at crucial stages of membrane excitability
      development is an important characteristics of NG108-15 cell differentiation,
      providing insights into the neural development and the reversible nature of
      neoplasia in the nervous system.

PMID- 9554995
TI  - Participation of hippocampal formation in negative feedback inhibition of penile
      erection in the rat.
AB  - Detailed information on how the central nervous system regulates penile erection,
      particularly the inhibitory aspect, is sparse. We observed in Sprague-Dawley rats
      anesthetized and maintained with chloral hydrate that administration of
      papaverine (400 microg) directly into the corpora cavernosum of the penis
      produced an increase in intracavernous pressure (ICP). This elicited experimental
      index for penile erection was accompanied by a transient increase in the root
      mean square values, concurrent with a shift in the contribution of Theta
      (increase) and delta (decrease) power to the hippocampal electroencephalographic
      (hEEG) activity. Reversal blockade of these hEEG responses with xylocaine, given
      either intrathecally at the L6-S1 spinal levels or unilaterally to the
      hippocampal formation, significantly heightened and prolonged the ICP response.
      Pretreatment with xylocaine by itself, however, did not alter appreciably the
      baseline ICP or hEEG activity. These results suggest the presence of a novel
      negative feedback inhibitory mechanism in the hippocampal formation, which is
      triggered by ascending sensory inputs initiated by tumescence of the penis during
      normal erectile processes.

PMID- 9554996
TI  - Prolonged anoxic depolarization exacerbates NADH hyperoxidation and promotes poor
      electrical recovery after anoxia in hippocampal slices.
AB  - Mitochondrial dysfunction appears to occur during brain ischemia and following
      reperfusion. A characteristic event during reoxygenation after anoxia in
      hippocampal slices is hyperoxidation of the electron carriers of the
      mitochondrial respiratory chain. Earlier studies suggested that calcium influx
      due to loss of ion homeostasis during anoxia was linked to neuronal damage. Since
      a link between cytosolic calcium overload and post-anoxic hyperoxidation (PAMHo)
      has been suggested in previous studies, present studies sought to test the
      hypothesis that the length of anoxic depolarization can influence hyperoxidation
      and electrical activity recovery following anoxia in hippocampal slices. Rat
      hippocampal slices were made anoxic and then allowed to recover for 60 min. The
      time of anoxia was defined by the time of anoxic depolarization (AD), and slices
      were divided in five groups: 0.5, 1, 2, 5 and 10 min of AD. Reduction/oxidation
      shifts of NADH were measured by rapid scanning spectrofluorometry. Synaptic
      activity was indicated by population spike amplitudes in the CA1 pyramidal cell
      subfield of the hippocampus in response to stimulation of the Schaffer
      collaterals. We report here that mitochondrial hyperoxidation and synaptic
      activity in hippocampal slices are highly sensitive to the time in which slices
      remain depolarized (AD).

PMID- 9554997
TI  - Development of dynorphin-like immunoreactive auditory nerve terminals in the
      chick.
AB  - The novel discovery that auditory nerve terminals in the chick cochlear nucleus
      magnocellularis (NM) are immunoreactive for the opioid peptide dynorphin (DYN)
      was recently reported [3]. The present study examines the development of DYN
      immunoreactivity (DYN-I) in auditory nerve terminals in NM from embryos through
      young post-hatch chicks. No DYN-I was observed in NM at embryonic day 13 (E13).
      DYN-I first appeared at E16 as short flat structures partially surrounding NM
      cell bodies. Around post-hatch day 1 (P1), these structures had a more rounded,
      chalice-type of morphology reminiscent of the specialized auditory nerve
      terminals found in birds, the end-bulbs of Held. At P6, most NM neurons were
      circumscribed by a prominent DYN-I calyceal-type of ending. By P13, fewer NM
      cells were ringed by this DYN-I and by the third post-hatch week, there was very
      little DYN-I in NM. There were no obvious differences in the density of DYN-I
      terminals across either the rostrocaudal length or the mediolateral width of NM
      at any age examined. These results suggest that during a restricted time of
      development, end-bulbs of Held in the chick NM contain DYN.

PMID- 9554998
TI  - Phospholipases A2 of rod outer segment-free bovine retinae are different from
      well-known phospholipases A2.
AB  - We have recently demonstrated the presence of phospholipase A2 (PLA2) activity in
      a rod outer segment-free retinal fraction which we called P200 and which contains
      neuronal cells, Muller cells and rod inner segments. We report here our results
      on the characterization of this P200-PLA2 activity. We show that P200 probably
      contains more than one type of PLA2, as indicated by the results obtained with
      different chromatographically eluted PLA2-active fractions which were treated
      with either Ca2+, EGTA, dithiothreitol (DTT) or p-bromophenacyl bromide (pBPB),
      or heated. Moreover, the results from PLA2 assays using different substrates, as
      well as those obtained after treatment of the homogenate with H2SO4, guanosine 5'
      O-(3-thio)triphosphate (GTPgammaS) and ATP, suggest that P200-PLA2 are different
      from well-known secretory PLA2, cytosolic PLA2 and Ca2+-independent PLA2. Control
      experiments using our 'back-and-forth'-thin layer chromatography (bf-TLC)
      technique allowed us to confirm that, in our assay conditions, the release of
      fatty acids was due to PLA2 enzymes. These results, which constitute the first
      characterization of PLA2 of the neural retina, thus suggest that it contains
      novel types of PLA2 enzyme, in contrast to well-known PLA2.

PMID- 9554999
TI  - Microinjections of anisomycin into the intermediate cerebellum during learning
      affect the acquisition of classically conditioned responses in the rabbit.
AB  - The purpose of this study was to examine the effects of protein synthesis
      inhibition in the intermediate cerebellum on the acquisition and expression of
      classically conditioned nictitating membrane responses in the rabbit. Animals
      were conditioned for three days in a standard delay paradigm. Before each
      training session, either a solution of anisomycin (a protein synthesis inhibitor)
      or vehicle was bilaterally injected into the interposed cerebellar nuclear.
      Following these three training sessions, rabbits were tested to determine whether
      the previous training under the influence of anisomycin or vehicle resulted in
      the acquisition of conditioned responses. In this test, animals that were
      injected previously with the protein synthesis inhibitor exhibited significantly
      less retention of conditioned responses than rabbits injected with vehicle.
      Additional experiments demonstrated that anisomycin does not block the expression
      of conditioned responses during conditioning or in well-trained animals.
      Microinjections of muscimol at the same sites of the previous drug infusions
      suppressed the expression of conditioned responses, indicating that the protein
      synthesis inhibitor was applied to the eyeblink-related parts of cerebellar
      circuits. The obtained data are the first to demonstrate that a manipulation of
      cerebellar circuits, which does not affect the performance of learned behavior,
      can affect the process of learning. These results suggest that the synthesis of
      new proteins in the intermediate cerebellum participates in the formation of
      plastic changes responsible for eyeblink conditioning.

PMID- 9555000
TI  - Parasympathetic varicosity proliferation and synaptogenesis in rat eyelid smooth
      muscle after sympathectomy.
AB  - Parasympathetic innervation to eyelid smooth muscle inhibits sympathetic
      neurotransmission pre-junctionally without appreciable direct post-junctional
      effects. However, 5 weeks after sympathectomy, parasympathetic stimulation
      elicits substantial cholinergically mediated contractions. This study examined
      ultrastructural changes accompanying the conversion to parasympathetic
      excitation. In intact muscles, 64+/-9 nerve varicosities were encountered per 104
      micron2. Most were close to muscle cells and not fully enclosed by supporting
      cells. Axo-axonal synapses were observed occasionally. Two days following
      sympathectomy, varicosity numbers were reduced by 97% and, relative to controls,
      remaining varicosities were farther from muscle cells and more frequently fully
      enclosed by supporting cells, but contained greater numbers of small spherical
      and large dense vesicles. By 6 weeks post-sympathectomy, numbers of varicosities
      per unit muscle volume increased to 14% of controls. These varicosities differed
      from those at 2 days in being closer to smooth muscle cells, less frequently
      enclosed, and having fewer small vesicles. These findings indicate that intact
      eyelid smooth muscle varicosities are predominantly sympathetic, but a small
      number of parasympathetic varicosities are present, some of which may form pre
      junctional synapses with sympathetic nerves. Between 2 days and 6 weeks post
      sympathectomy, varicosities increased in number and established appositions with
      smooth muscle cells. This suggests that parasympathetic nerves are capable of re
      innervating an atypical smooth muscle target after sympathectomy, and that
      parasympathetic synaptogenesis is likely to contribute to conversion from pre
      junctional inhibition to post-junctional excitation after sympathectomy.

PMID- 9555001
TI  - NMDA receptor activation enhances the release of a cholinergic differentiation
      peptide (HCNP) from hippocampal neurons in vitro.
AB  - Hippocampal cholinergic neurostimulating peptide (HCNP) is a novel undecapeptide
      purified from the hippocampus of young rats. The peptide stimulates cholinergic
      phenotype development in the rat medial septal nucleus in vitro. Here, we have
      focused on the mechanism of release of the peptide from the hippocampus, by
      applying tissue culture techniques. Quantitation of HCNP in the culture
      supernatant after chemical stimulation was carried out by RIA, and by a
      combination of HPLC and RIA. We found that the N-methyl-D-aspartate (NMDA)
      receptor specifically mediates release of the deacetylated form of HCNP from the
      culture. Our results suggest that during the early development of hippocampal
      neurons, the peptide is released by NMDA receptor activation, and that it may be
      involved in mediating the effect of activity-dependent cues on developing septal
      cholinergic neurons.

PMID- 9555002
TI  - Pharmacological characterisation of the histamine H3 receptor in the rat
      hippocampus.
AB  - The purpose of this report was to pharmacologically characterise the histamine H3
      in the rat hippocampus using radioligand binding studies with the H3 receptor
      antagonist [125I]iodophenpropit and the H3 receptor mediated inhibition of
      [3H]noradrenaline release. A dissociation constant of 0.33 nM and a maximal
      number of binding sites of 125 fmol/mg protein were found for
      [125I]iodophenpropit. Competition studies showed stereoselectivity for the (R)
      and (S) enantiomers of alpha-methylhistamine and 10 microM of GTPgammaS shifted
      the curve of (R)-alpha-methylhistamine rightwards. Up to 1 microM, (R)-alpha
      methylhistamine displaced only 30% whereas the tested H3-antagonists displaced 50
      60% of the total [125I]iodophenpropit bound. This indicates the presence of an
      additional non-H3 receptor binding site(s) for [125I]iodophenpropit in the rat
      hippocampus. This secondary site shows low affinity for H3 agonists, but high
      affinity for the tested H3 antagonists. Electrically evoked [3H]acetylcholine
      release was shown in slices of rat hippocampus. No H3 receptor modulation of
      [3H]acetylcholine release from hippocampal slices was detectable. However, H3
      receptor activation inhibited 42% of the electrically-evoked [3H]noradrenaline
      release in rat hippocampal slices. The inhibition of [3H]noradrenaline release
      was effectively antagonized by the H3 antagonists thioperamide and burimamide. We
      describe the pharmacological identification of the histamine H3 receptor in the
      rat hippocampus and its similarities and differences from the cortical H3
      receptor. These studies enable us to investigate changes in density and
      functionality of the hippocampal H3 receptor under (patho)physiological
      conditions.

PMID- 9555003
TI  - Vesicular amine transporter expression and isoform selection in developing brain,
      peripheral nervous system and gut.
AB  - The vesicular monoamine transporters VMAT1 and VMAT2 are essential components of
      monoaminergic neurons and endocrine cells whose expression in development may
      provide insight into lineage pathways for chemical coding in the diffuse
      neuroendocrine system. Thus, the brain is a compartment in which only
      monoaminergic neurons are generated, the gut epithelium generates only endocrine
      monoamine-containing cells, and the neural crest produces both autonomic
      monoaminergic neurons and endocrine/paracrine monoaminergic cells. Selection of
      either the VMAT1 or VMAT2 isoform was examined in these three compartments during
      development. In the central nervous system VMAT2, but not VMAT1, was expressed in
      neuroepithelial cells by embryonic day 12 (E12), and all major monoaminergic cell
      groups by E14. Thalamocortical and hypothalamic neurons that do not express VMAT2
      in adulthood were transiently VMAT2-positive from E16 to postnatal day 6 (P6). EC
      cells of the gut expressed exclusively VMAT1 from E19 on, while histamine
      containing enterochromaffin-like (ECL) cells of the stomach expressed only VMAT2
      by E19 and throughout postnatal development. VMAT2 and the vesicular
      acetylcholine transporter VAChT were co-expressed in early development of the
      primary sympathetic chain as well as in the cranial parasympathetic ganglia.
      VAChT was progressively restricted to a small population of VMAT2-negative post
      ganglionic neurons in the adult sympathetic chain, while VMAT2 expression
      persisted in sympathetic principal ganglion and SIF cells but was eventually
      extinguished in cranial parasympathetic ganglia. VMAT1 was co-expressed with
      VAChT and VMAT2 mRNA in the primary sympathetic chain on E12, but progressively
      restricted to small intensely fluorescent (SIF) and chromaffin cells thereafter.
      Thus, expression of the vesicular amine transporters appropriate for chemical
      coding of brain neurons and gut endocrine cells are pre-determined
      developmentally. In contrast, the neural crest-derived sympathoadrenal and neural
      crest-derived parasympathetic cell groups examined here initially co-express two
      or more vesicular amine transporters, followed by extinction of the inappropriate
      transporter(s) later in development. Some neural crest-derived neuroendocrine
      cell populations continue to express both isoforms of VMAT even in adulthood.
      Lineage distinctions in ontogeny of vesicular amine transporter expression in
      brain, gut and autonomic nervous system make it likely that the same genes are
      regulated differently in the autonomic nervous system compared to brain and gut.

PMID- 9555004
TI  - Differential expression of calbindin and calmodulin in motoneurons after
      hypoglossal axotomy.
AB  - Axotomy induces a profound modification of Ca2+ homeostasis in injured neurons
      which may lead to neuronal death. Remarkably, after axotomy and resection of the
      hypoglossal nerve, 65-75% of the hypoglossal motoneurons survive in the long term
      and this suggests some adaptive mechanisms compensating the massive calcium
      influx. As potential components of this adaptation, we have examined calmodulin
      and calbindin-D28k by in situ hybridisation and immunohistochemistry in
      motoneurons of the rat after hypoglossal nerve transection. Neuronal calbindin
      mRNA and protein content was low in normal state, transiently increased to 200%
      of the basal expression at 8 days post-operation (dpo), then declined to normal
      again until 28 dpo. Calmodulin mRNA was highly expressed in normal hypoglossal
      motoneurons and remained constant after axotomy. Calmodulin protein
      immunoreactivity, however, was transiently decreased in axotomised motoneurons
      suggesting post-transcriptional modification. The upregulation of calbindin
      expression may facilitate the survival of injured motoneurons.

PMID- 9555006
TI  - Expression of substance P receptor in the substantia nigra.
AB  - Since the substantia nigra receives abundant substance P innervations but lacks
      clear evidences about a presence of substance P receptors, expressions for mRNA
      and protein of substance P receptors were investigated in the rat to resolve this
      mismatch. Expression levels of substance P receptors mRNA in the substantia nigra
      pars compacta and reticulata were 37.7 and 24.1% of those in the striatum,
      respectively, by reverse transcription-polymerase chain reaction (RT-PCR).
      Substance P receptors mRNA was found in dopamine neurons of the substantia nigra
      pars compacta by single cell RT-PCR. Ca. 90% of dopamine neurons in the
      substantia nigra pars compacta were immunoreactive to anti-substance P receptor
      antibody in the colchicine treated rats. These are the first direct evidence for
      the existence of substance P receptors in dopamine neurons of the substantia
      nigra pars compacta.

PMID- 9555005
TI  - Oxidative modification of HDL3 in vitro and its effect on PLTP-mediated
      phospholipid transfer.
AB  - The oxidation of HDL3 by Cu(II) and its effect on the ability of these particles
      to act as phospholipid acceptors in human plasma phospholipid transfer protein
      (PLTP)-mediated lipid transfer were investigated. Oxidation of HDL3 was monitored
      by measuring the following parameters: (i) formation of conjugated dienes, (ii)
      production of thiobarbituric acid reactive substances (TBARS), (iii) decrease in
      reactive lysine and (iv) tryptophan residues, (v) change in particle charge and
      (vi) diameter, and (vii) oligomerisation of apoA-I and apoA-II. Formation of
      conjugated dienes was the parameter responding to the oxidative treatment with
      the fastest kinetics. The appearance of TBARS and modification of apolipoprotein
      tryptophan residues were detected simultaneously but required higher Cu(II)
      concentrations for maximal kinetics. Cross-linking of the major protein
      constituents of HDL3, apoA-I and apoA-II, represented later steps of the
      oxidation process. Further, the oxidative modification was accompanied by a
      progressive change in HDL3 particle charge and a minor increase in particle
      diameter. PLTP-mediated phospholipid transfer to the oxidized particles was
      investigated using an assay measuring the transfer of fluorescent, pyrene-labeled
      PC. The transfer was significantly inhibited, but only after extensive
      modification of the HDL proteins, suggesting that the HDL oxidative modifications
      occurring in vivo do not essentially impair its phospholipid acceptor function. A
      similar but less pronounced inhibition was observed when two other phospholipid
      transfer proteins, the nonspecific lipid transfer protein (ns-LTP) and the
      phosphatidylcholine transfer protein (PC-TP), were studied in parallel. This
      indicates that the inhibition was partly due to unspecific effects of the
      modification on acceptor particle surface properties, but included an aspect
      specific for PLTP.

PMID- 9555007
TI  - Laminin inhibits Abeta42 fibril formation in vitro.
AB  - In the present study, we investigated whether or not laminin inhibits Abeta42
      fibril formation in the same manner as Abeta40. Both a thioflavine-T fluorometric
      assay and electron microscopy by negative staining demonstrated laminin to have a
      concentration-dependent inhibitory effect on Abeta42 fibril formation. The
      amyloid fibril formation was inhibited approximately by 70% due to the presence
      of 1.0 mg/ml laminin co-incubated with 1. 0 mg/ml Abeta42 peptide (molar ratio;
      Abeta42 peptide:laminin=200:1). These results thus suggested that laminin or its
      derivatives may be effective as therapeutic agents to either prevent or slow down
      the progression of amyloidogenesis in Alzheimer's disease.

PMID- 9555008
TI  - The 5-HT3 receptor agonist attenuates the action of antidepressants in the forced
      swim test in rats.
AB  - Involvement of 5-hydroxytryptamine (5-HT)3 receptors in action of antidepressants
      was examined in the forced swim test in rats. Rats were forced to swim in a
      cylinder for 15 min on day 1 and for 5 min on day 2. Imipramine, desipramine and
      mianserin, administered after the 15-min swim session on day 1 and before the 5
      min swim test on day 2, dose-dependently decreased the duration of immobility in
      the swim test on day 2. 1-(m-Chlorophenyl)-biguanide (mCPBG) attenuated the
      decreased duration of immobility induced by imipramine, desipramine and
      mianserin, although mCPBG did not affect the duration of immobility when it was
      given alone. ICS205-930 dose-dependently decreased the duration of immobility in
      the swim test on day 2, and the effect of ICS205-930 was attenuated by mCPBG.
      These results suggest that the suppression of 5-HT3 receptor activity may
      contribute to the action of antidepressants.

PMID- 9555009
TI  - Diffusion, perfusion, and T2 magnetic resonance imaging of anti-intercellular
      adhesion molecule 1 antibody treatment of transient middle cerebral artery
      occlusion in rat.
AB  - The effect of anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibody
      treatment of transient (2 h) middle cerebral artery (MCA) occlusion in the rat
      was measured using diffusion (DWI)-, T2 (T2I)- and perfusion (PWI)-weighted
      magnetic resonance imaging. Rats were treated upon reperfusion with an anti-ICAM
      1 monoclonal antibody (n=11) or a control antibody (n=7). DWI, T2I and PWI were
      performed before, during, and after induction of focal cerebral ischemia from 1 h
      to 7 days. In both groups, the apparent diffusion coefficient of water (ADCw) and
      cerebral blood flow (CBF) values in the ischemic region significantly declined
      from the preischemic ADCw values (p<0. 05). The post ischemic increase in T2 of
      the control group was significantly higher at 48 h than in the anti-ICAM-1
      treated group (p<0.05). CBF was not significantly different between the two
      groups. The temporal profiles of MRI cluster analysis, which combines ADCw and T2
      maps into a single image, was significantly different between groups. These data
      suggest that the neuroprotective effect of anti-ICAM-1 antibody treatment is
      reflected in reductions of T2 and lesion growth during reperfusion and may not be
      associated with increased cerebral perfusion.

PMID- 9555010
TI  - Molecular cloning, functional expression and tissue distribution of rat acyl
      coenzyme A:cholesterol acyltransferase.
AB  - Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an enzyme catalyzing the
      intracellular formation of cholesteryl esters from free cholesterol and fatty
      acyl-CoA. In the present study, we cloned rat ACAT cDNA and determined its tissue
      distribution. Rat ACAT cDNA, having a coding region of 1635 bp with its deduced
      protein sequence of 545 amino acids and two typical motifs such as signature
      sequences and leucine heptad motif, showed 83, 92 and 90% identity with human,
      mouse, and hamster ACAT, respectively. Expression of rat ACAT cDNA in A293 cells
      and CHO cells resulted in a 3.0 to 3.5-fold increase in the enzyme activity.
      Among twelve tissues examined, ACAT activity was highest in adrenal followed by
      liver and intestine while that of aorta was extremely low. The mRNA level was
      also the highest in adrenal among four tissues examined. However, in contrast to
      its high ACAT activity, the liver mRNA level was extremely low (adrenal >>
      intestine > aorta >> liver). Consistent with mRNA levels, immunohistochemical
      analyses with a specific ACAT antibody detected significant ACAT signals in
      adrenal and intestine but a negligible signal in liver. These results indicate
      that adrenal most abundantly expresses ACAT in rat. Furthermore, rat liver showed
      a high ACAT activity but an extremely low ACAT mRNA and negligible
      immunohistochemical reactivity, suggesting the presence of a structurally
      different ACAT protein(s) in rat liver.

PMID- 9555011
TI  - Effects of extracellular calcium and magnesium on central respiratory control in
      the brainstem-spinal cord of neonatal rat.
AB  - The influence of extracellular Ca2+ and Mg2+ concentrations ([Ca2+]ECF and
      [Mg2+]ECF, respectively) on central respiratory control was analyzed using the
      isolated brainstem-spinal cord of the neonatal rat. Central respiratory activity
      was recorded from the C4 ventral roots. The depth profile of [Ca2+]ECF below the
      ventral medullary surface was measured with ion-sensitive electrodes. The
      gradient in [Ca2+]ECF disappeared about 1 h after changing superfusate Ca2+
      ([Ca2+]CSF) from 2 to 0.5 mM, but not even in 2 h after switching to Ca2+-free
      superfusate. High [Ca2+]CSF (4 mM) or high [Mg2+]CSF (4, 8 mM) decreased
      respiratory frequency (fR), whereas low [Ca2+]CSF (0.5 mM) increased fR and
      augmented the respiratory CO2 responsiveness. High [Ca2+]CSF as well as low
      [Mg2+]CSF (0.5 mM) disturbed respiratory rhythm and pattern, which were markedly
      restored by high CO2. The depressing effect of high [Ca2+]ECF and the stimulating
      effect of low [Ca2+]ECF on the medullary neuronal activity were confirmed by
      perforated patch recordings. These results suggest that [Ca2+]ECF and [Mg2+]ECF
      determine the excitability of the respiratory neuron network by modulating the
      neuronal surface potential, transmembrane Ca2+ influx, Ca2+-sensitive cation
      channel gating, and synaptic transmission. Furthermore, some of these actions
      appear to be antagonized by CO2/H+.

PMID- 9555012
TI  - Localization of 5-HT2A receptor in rat cerebral cortex and olfactory system
      revealed by immunohistochemistry using two antibodies raised in rabbit and
      chicken.
AB  - Serotonin 2A receptor (5-HT2A receptor) is widely distributed in the central
      nervous system, and has been suggested to be involved in a variety of behavioral
      conditions and neuropsychiatric disorders. Two polyclonal antibodies were raised
      against the N-terminus peptide of rat 5-HT2A receptor in chickens (5-HT2A-N) and
      a glutathione S-transferase fusion protein that contained the C-terminus of the
      mouse 5-HT2A receptor in rabbits (5-HT2A-C). Affinity-purified 5-HT2A-N and -C
      antibodies reacted strongly with a single band of 77-78 kDa in postsynaptic
      density proteins prepared from the rat cortex. The distribution pattern of
      immunoreactive structures in the rat brain was virtually the same for the two
      antibodies. The highest levels of immunoreactivity were observed in the olfactory
      bulb, neocortex, claustrum, piriform cortex, mamillary bodies, pontine nuclei,
      red nucleus and cranial motor nuclei. In the olfactory bulb, mitral cells were
      intensely labeled. In the neocortex, many immunoreactive neurons were found in
      layers II-VI. In layer IV of the neocortex, strong neuropil labeling was
      observed. In a double-labeling study using chicken 5-HT2A-N and rabbit anti-glial
      fibrillary acidic protein (GFAP) antibody, a considerable number of GFAP positive
      cells also showed 5-HT2A immunoreactivity. By using an immunoelectron microscopic
      technique, 5-HT2A receptor immunoreaction was shown to be localized just beneath
      the postsynaptic membrane thickening of asymmetric synapses.

PMID- 9555013
TI  - Transplanted embryonic entorhinal neurons make functional synapses in adult host
      hippocampus.
AB  - Grafts of embryonic entorhinal cortex (EC) or non-entorhinal cortex (NEC) were
      placed into the hippocampus of adult rats with transection of the perforant
      paths. Graft-host connectivity was investigated at 4-6 months post
      transplantation by recording extracellular evoked responses in hippocampal slice
      preparations. Electrical stimulation of the grafts evoked excitatory postsynaptic
      potentials (EPSPs) in the outer molecular layer of the dentate gyrus, and the
      stratum lacunosum moleculare of CA1, CA3, and elicited population spikes in the
      granule cell layer and the pyramidal cell layer of CA1, but not CA3. While the
      latencies and the forms of these evoked response were similar to those in matched
      control slices from the normal animals, the amplitudes were smaller than normal
      controls. However, in the slices with NEC grafts, no such responses were recorded
      when stimulus was applied in similar position in the grafts. The findings suggest
      that grafted entorhinal neurons make viable synaptic connections with the host
      hippocampus.

PMID- 9555014
TI  - Indirect dexamethasone down-regulation of the liver fatty acid-binding protein
      expression in rat liver.
AB  - The effects of glucocorticoids on the regulation of the liver fatty acid-binding
      protein (L-FABP) were studied in vivo and in primary culture of hepatocytes in
      rats. No change in L-FABP cytosolic content and mRNA levels occurred after
      adrenalectomy. By contrast, a twofold decrease in L-FABP expression was found in
      dexamethasone (Dex) treated rats. In primary culture of rat hepatocytes, insulin
      did not modify the L-FABP mRNA levels, whereas Dex produced a significant
      decrease. This down-regulation was independent of specific glucocorticoid
      receptors, of alteration in the turnover of L-FABP mRNA and did not require a de
      novo protein synthesis. However, it was totally prevented when 320 microM oleic
      acid was added in the culture medium. These findings show that the dex-mediated
      down-regulation of the L-FABP expression found in vivo is not due to a direct
      endocrine effect, but is likely secondary to changes in cellular lipid
      metabolism.

PMID- 9555015
TI  - Composition of ibotenic acid-induced calcifications in rat substantia nigra.
AB  - Agonists of the excitatory neurotransmitter glutamate have neurotoxic properties
      and are, therefore, frequently used to place locally circumscript brain lesions.
      In certain vulnerable brain areas, especially the substantia nigra and globus
      pallidus, the ensuing neurodegeneration is accompanied by the formation of
      calcium deposits. In the present study, we investigated the structure and
      chemical composition of calcium deposits formed in rat substantia nigra upon
      local application of ibotenic acid. Using scanning and transmission electron
      microscopy in combination with X-ray analysis and analysis of the electron
      diffraction patterns, we demonstrate that the inorganic components of the
      calcifications consist of calcium and phosphate. The calcium phosphate is
      deposited in a polycrystalline manner in degenerating neurons and in a matrix
      surrounding the degenerated complexes. New matrix is continuously added around
      the enlarging calcium deposits. Content of inorganic material is always higher in
      the center of the deposits than in the margin, but in every case the diffraction
      pattern reveals that the calcium phosphates are present in the form of
      hydroxyapatite. Thus, organic and inorganic components of the calcifications are
      subject to a continuous process of growth and maturation. The ibotenic acid
      induced calcium deposits in rat substantia nigra provide a reliable model system
      to study the pathogenesis of non-arteriosclerotic calcifications.

PMID- 9555016
TI  - Midkine exists in astrocytes in the early stage of cerebral infarction.
AB  - Midkine (MK), a heparin-binding neurotrophic factor, is expressed in the early
      stage of experimental cerebral infarction in the zone surrounding the infarct.
      Double immunostaining with anti-MK and anti-glial fibrillary acidic protein
      showed existence of MK in astrocytic cytoplasm on postoperative day 2.
      Immunoelectron microscopic analysis revealed the presence of MK in the swollen
      astrocytic processes on postoperative day 4.

PMID- 9555017
TI  - Serotonergic activity in the rat striatum after intrastriatal transplantation of
      fetal nigra as measured by microdialysis.
AB  - In vivo microdialysis was used to examine the effects of dopaminergic transplants
      on extracellular concentrations of dopamine (DA), serotonin (5-HT), and their
      precursors and major metabolites in the denervated rat striatum. Dialysis
      perfusates were collected from intact 6-hydroxydopamine (6-OHDA) lesion plus sham
      grafted, and lesion plus fetal substantia nigra (SN) grafted striata. The SN
      transplants ameliorated the reduction of striatal DA and dihydroxyphenylacetic
      acid (DOPAC) levels in rats with unilateral 6-OHDA lesions of the mesostriatal
      pathway. The transplants also increased extracellular levels of 5-HT and 5
      hydroxyindoleacetic acid (5-HIAA) in the denervated striatum. In response to NSD
      1015 (an inhibitor of aromatic L-amino acid decarboxylase, AADC), 5
      hydroxytryptophan (5-HTP) levels were substantially elevated in the SN grafted
      striata as compared with those in the sham grafted controls, which continued even
      after subsequent administration of L-3,4-dihydroxyphenylalanine (L-DOPA, 100
      mg/kg i.p.). Immunohistochemical analysis showed hyperinnervation of 5-HT fibers
      in the grafted striatum, which was consistent with the results of microdialysis
      experiments. These results indicated that implantation of SN grafts into the 6
      OHDA-lesioned striatum of rats induces hyperactivity of 5-HT synthesis, release
      and metabolism.

PMID- 9555018
TI  - The development of synaptophysin-like immunoreactivity in the lumbosacral
      enlargement of the spinal cord of the opossum Monodelphis domestica.
AB  - The presence of synaptophysin in the lumbosacral enlargement of developing
      opossums, Monodelphis domestica, was studied immunohistochemically at the light
      microscopic level. In newborn, synaptophysin-labeling was observed in the
      presumptive white matter, presumably in growing axons, and was scant in the
      ventrolateral gray matter. Over the next 3 weeks the labeling filled the gray
      matter following a general ventrodorsal gradient. Labeling was found in the white
      matter until the fifth week. Synaptogenesis in the lumbosacral enlargement of the
      opossum thus occurs mostly postnatally, when many descending axons have already
      reached that level. It is particularly intense in the ventral horn when the
      hindlimbs begin to move, and in the dorsal horn when sensorimotor reflexes can be
      elicited.

PMID- 9555019
TI  - Alzheimer-associated presenilin-1 gene is induced in gerbil hippocampus after
      transient ischemia.
AB  - To investigate the biological roles of the presenilin-1 (PS-1) gene after
      neuronal injury, the changes of PS-1 mRNA expression in the gerbil hippocampus
      after transient ischemia were examined. From 1 day to 3 day-reperfusion after 5
      min-ischemia, PS-1 mRNA was induced in the hippocampus compared with the sham
      operated control. The cells which induced the PS-1 genes were neurons of CA3 and
      dentate gyrus, the region relatively resistant to ischemic stress. These findings
      suggest that the induction of PS-1 genes may be associated with some responses of
      neurons damaged by transient ischemia.

PMID- 9555021
TI  - Effects of haloperidol metabolites on neurotransmitter uptake and release:
      possible role in neurotoxicity and tardive dyskinesia.
AB  - This research explored the effects of haloperidol (HP) metabolites on biogenic
      amine uptake and release, and compared them to those of MPTP and its toxic
      metabolite, MPP+. In synaptosome preparations from mouse striatum and cortex, the
      HP metabolites haloperidol pyridinium (HPP+), reduced haloperidol pyridinium
      (RHPP+), and haloperidol tetrahydropyridine (HPTP) inhibited the presynaptic
      uptake of dopamine and serotonin, with greater affinity for the serotonin
      transporter. HPP+ was the most potent inhibitor of dopamine uptake, and HPTP of
      serotonin uptake, both with IC50 values in the low micromolar range. RHPP+ was
      less active than the other metabolites, but was more active than the parent
      compound, HP. Inhibition of uptake was reversed when free drug was removed by
      centrifugation and then resuspension of the synaptosomes in fresh buffer,
      suggesting that inhibition of uptake was due to interaction with the transporters
      and was not due to irreversible cytotoxicity. HPP+ showed noncompetitive
      inhibition of both serotonin and dopamine uptake, suggesting that it has a
      relatively slow dissociation rate for its interaction with the transporter
      proteins. In experiments on amine release, HPP+ and HPTP were four-fold less
      potent than MPP+ for releasing preloaded dopamine from striatal synaptosomes, and
      only MPP+-dependent release was antagonized by the uptake blocker, mazindol. In
      contrast, RHPP+ displayed little ability to release either amine
      neurotransmitter. HPTP was about two-fold more potent than MPP+ for releasing
      serotonin from cortical synaptosomes, whereas HPP+ was less active than MPP+. The
      specific serotonin transport blocker fluoxetine was only able to antagonize
      release induced by MPP+. These results suggest that HP metabolites bind to the
      transporters for dopamine and serotonin, but are not transporter substrates. In
      contrast to their potent effects on amine release, HPP+ and HPTP were unable to
      release preloaded GABA from cortical synaptosomes. The implications of these
      results concerning a possible role of HP metabolites in the development of
      tardive dyskinesia are discussed.

PMID- 9555020
TI  - Platelet-derived growth factor and fibroblast growth factor differentially
      regulate interleukin 1beta- and cAMP-induced group II phospholipase A2 expression
      in rat renal mesangial cells.
AB  - Expression of group II phospholipase A2 (PLA2; EC 3.1.1.4) in rat renal mesangial
      cells is triggered in response to two principal classes of activating signals.
      These two groups of activators comprise inflammatory cytokines such as
      interleukin 1beta (IL-1beta) or tumor necrosis factor alpha and agents that
      elevate cellular levels of cyclic AMP (cAMP) such as forskolin, an activator of
      adenylate cyclase. Treatment of mesangial cells with IL-1beta or forskolin for 24
      h induces group II PLA2 activity secreted into cell culture supernatants by about
      15-fold and 11-fold, respectively. Platelet-derived growth factor (PDGF)-BB
      potently inhibits secretion of IL-1beta- and forskolin-induced group II PLA2
      activity. By Western and Northern blot analyses, we demonstrate that this is due
      to a reduction of PLA2 protein levels and the corresponding PLA2 mRNA steady
      state levels. Basic fibroblast growth factor (bFGF) virtually does not inhibit IL
      1beta-stimulated group II PLA2 activity, but markedly inhibits forskolin-induced
      expression of group II PLA2 activity. These effects are caused by changes in the
      corresponding PLA2 protein and PLA2 mRNA steady-state levels. Inhibition of
      protein kinase C (PKC) by the potent and selective PKC inhibitor calphostin C
      converted the inhibitory action of PDGF into a bFGF-type of response thus
      suggesting that PKC is a major effector in PDGF-induced inhibition of IL-1beta
      stimulated group II sPLA2 expression. In summary, our data suggest that PDGF and
      bFGF differentially modulate in a stimulus-specific manner the expression of
      group II PLA2 in mesangial cells.

PMID- 9555022
TI  - RU-486 blocks stress-induced enhancement of proenkephalin gene expression in the
      paraventricular nucleus of rat hypothalamus.
AB  - The purpose of this study was to investigate the glucocorticoid (GC) mediated
      regulation of corticotropin-releasing hormone (CRH) and proenkephalin (PE) gene
      expressions in the paraventricular nucleus (PVN) of the hypothalamus during
      physical stress induced by a single intraperitoneal (i.p.) injection of
      hypertonic saline (9% NaCl). Previous intracerebroventricular (i.c.v.)
      administration of the type II glucocorticoid receptor (GR) antagonist RU-486 (20
      ng/rat), increased the basal CRH mRNA levels in the PVN but had no effect on PE
      gene expression. Stress induced by injection of hypertonic saline increased both
      CRH and PE mRNA levels in PVN. Administration of RU-486 completely blocked the
      stress-induced increase of PE mRNA levels, but failed to alter the CRH mRNA
      levels in the PNV. These data suggests that, under these experimental conditions,
      endogenous GC are necessary for a normal PE response to hypertonic saline stress.

PMID- 9555023
TI  - Postnatal conditioning for spreading cortical depression in the rat brain.
AB  - The cerebral cortex of anaesthetised 2- to 12-day-old rats was superfused with
      artificial cerebrospinal fluid containing 100 mM acetate substituted for chloride
      to condition the brain for spreading depression (SD). After such superfusion, the
      earliest SD-like events were found at day 9 and full blown SD at day 10, whereas
      in the unconditioned brain the first SD occurred between days 12 and 15. Acetate
      conditioning of the cerebral cortex may be used to unmask neuronal and glial
      properties that are hidden in early stages of development.

PMID- 9555024
TI  - Altered number of diaphorase (NOS) positive neurons in the hypothalamus of rats
      with heart failure.
AB  - Recently, we have demonstrated a decreased neuronal isoform of nitric oxide
      synthase (nNOS) message in the hypothalamus of rats with heart failure (HF). The
      purpose of this study was to determine the changes in NADPH-diaphorase (a
      commonly used marker for neuronal NOS activity) positive neurons in specific
      hypothalamic sites of rats with HF. After a standard histochemical protocol, NOS
      positive neurons were measured in paraventricular nucleus (PVN), supraoptic
      nucleus (SON), median preoptic area (MePO), subfornical organ (SFO), organum
      vasculosum of the lamina terminalis (OVLT) and lateral hypothalamus (LH) of rats
      with coronary artery ligation (HF group; n=8) and sham-operated control rats
      (n=9). A total of 4 months after coronary ligation, the rats in the HF group
      displayed infarcts greater than at least 35% of the left ventricular wall (n =
      8). Sham-operated rats had no observable damage to the myocardium. Rats with HF
      had a significantly lower number of NOS positive cells in the PVN (36% less)
      compared to sham rats. The number of NOS positive cells remained unaltered in the
      SON, MePO and LH in rats with HF. Conversely there was an increased number of NOS
      positive cells in the SFO (42% greater) and OVLT (100% greater). These data
      support the conclusion that the NO system within the hypothalamus involved in
      controlling autonomic outflow is altered during HF and may contribute to the
      elevated levels of vasopressin and sympatho-excitation commonly observed in HF.

PMID- 9555025
TI  - Isolation and characterization of a bovine neural specific protein (CRMP-2) cDNA
      homologous to unc-33, a C. elegans gene implicated in axonal outgrowth and
      guidance.
AB  - We have cloned the cDNA encoding bovine CRMP-2 from bovine brains. A full length
      cDNA encoding bovine CRMP-2 was isolated and sequenced. The deduced amino acid
      sequence reveals that the gene encodes a protein of 572 amino acids and is highly
      homologous to Caenorhabditis elegans unc-33, which controls the guidance and
      outgrowth of neuronal axons. The CRMP-2 transcript was present in bovine brains
      but not non-neural tissues, and its protein product existed in both soluble and
      membrane-bound forms. The expression of CRMP-2 protein and mRNA was upregulated
      during neuronal differentiation of rat PC12 cells. Immunoprecipitation of PC12
      cell extracts shows that CRMP-2 was co-immunoprecipitated with a 190 kDa protein
      (p190). Both CRMP-2 and p190 were phosphorylated on serine residues in vivo and
      in vitro in a kinase assay of CRMP-2 immune complexes. Immunocytochemistry shows
      that CRMP-2 was exclusively localized in both the central and peripheral nervous
      systems in mouse embryos and detectable in the adult brain although the level of
      CRMP-2 decreased. The protein was expressed in the axon, dendrite, and cytoplasm
      of postmitotic neurons and in the cytoplasm of oligodendrocytes and astrocytes.
      The CRMP-2 gene maps to the region of mouse chromosome 14 syntenic with human
      chromosome 8p21. Taken together, these data suggest multi-functional roles for
      CRMP-2 in developing and adult nervous systems, and the biological activity of
      CRMP-2 could be regulated by phosphorylation reaction.

PMID- 9555026
TI  - Squalene-hopene cyclase from Methylococcus capsulatus (Bath): a bacterium
      producing hopanoids and steroids.
AB  - We report the cloning and characterisation of the Methylococcus capsulatus shc
      gene, which encodes the squalene-hopene cyclase (SHC). This enzyme catalyses the
      complex cyclization of squalene to the pentacyclic triterpene skeleton of
      hopanoids and represents the key reaction in this biosynthesis. Using a
      combination of PCR amplification and DNA hybridization, two overlapping 2.6 kb
      PstI and 3.3 kb SalI DNA fragments were cloned bearing a 1962 bp open reading
      frame encoding a 74 kDa protein with 654 amino acids and a predicted isoelectric
      point at about pH 6.3. The deduced amino acid sequence of the M. capsulatus shc
      gene showed significant similarity to known prokaryotic SHCs and to a lesser
      degree to the related eukaryotic oxidosqualene cyclases (OSCs). Like other
      triterpene cyclases, the M. capsulatus SHC contains seven so-called QW-motifs as
      well as an aspartate-rich domain. The recombinant M. capsulatus SHC was expressed
      in Escherichia coli and in vitro activity of the recombinant cyclase was
      demonstrated using crude cell-free lysate or solubilized membrane preparation.
      The cyclization products hop-22-ene and hopan-22-ol (diplopterol) were identified
      by GC and GC-MS.

PMID- 9555027
TI  - A light and electron microscopic study of cytoplasmic phospholipase A2 and
      cyclooxygenase-2 in the hippocampus after kainate lesions.
AB  - The systemic administration of kainate (10 mg/ml) into adult Wistar rats produces
      seizures and neurodegeneration. We have studied the effect of kainate
      administration on cPLA2 and COX-2 immunoreactivities after 3 days and 1, 2, 4 and
      11 weeks. The cPLA2 immunoreactivity was increased in hippocampal neurons at 1
      and 3 days after kainate injection suggesting that PLA2 may be involved in
      neurodegeneration. Increased cPLA2 and COX-2 immunoreactivities in astrocytes at
      1, 2, 4 and 11 weeks after kainate injection indicate an adaptive astrocytic
      response that may be associated with gliosis.

PMID- 9555028
TI  - NMDA- and MK801-induced changes in dopamine release are attenuated in kainic acid
      lesioned nucleus accumbens of conscious rats: an in vivo microdialysis study.
AB  - Local application of N-methyl-d-aspartate (NMDA) and a NMDA receptor antagonist,
      MK801 through the dialysis membrane into the nucleus accumbens (NAC) caused a
      significant decrease and increase in extracellular dopamine (DA) in the NAC of
      conscious rats, respectively. These neurochemical changes were significantly
      smaller in the kainic acid (KA)-lesioned NAC than in the intact NAC. These
      findings show that locally applied NMDA and MK801 into the NAC modulate DA
      release mainly through indirect mechanism involving putative GABA neuron of the
      NAC.

PMID- 9555029
TI  - Adrenomedullin increases intracellular Ca2+ and inositol 1,4,5-trisphosphate in
      human oligodendroglial cell line KG-1C.
AB  - The effects of adrenomedullin (AM), a hypotensive peptide, were investigated in
      cultured human oligodendroglial cell line KG-1C. Human AM increased the
      intracellular Ca2+ concentration ([Ca2+]i) at concentrations greater than 10(-7)
      M. Human calcitonin gene-related peptide (CGRP), a peptide structurally related
      to AM, also increased [Ca2+]i with a potency similar to that of AM. AM increased
      [Ca2+]i in the absence of extracellular Ca2+. Further, AM increased inositol
      1,4,5-trisphosphate (Ins(1,4,5)P3) level in a concentration-dependent manner
      similar to that of AM-induced [Ca2+]i, suggesting that AM-induced elevation of
      [Ca2+]i is due to Ca2+ release from Ins(1,4,5)P3-sensitive stores. AM (10(-9) to
      10(-6) M) increased cAMP in a concentration-dependent manner. Forskolin also
      increased cAMP, but did not mimic the [Ca2+]i-raising effect of AM. These
      findings suggest that functional AM receptors are present in oligodendroglial KG
      1C cells and that AM increases [Ca2+]i through a mechanism independent of cAMP.

PMID- 9555030
TI  - Abnormal localization of iron regulatory protein in Alzheimer's disease.
AB  - A role for altered iron metabolism in the pathogenesis of Alzheimer's disease has
      been suggested by several reports associating the cardinal neuropathologic
      lesions with markers of free radical-induced damage and redox-active iron. We
      hypothesized that the abnormal distribution of iron in Alzheimer brain might
      result from alterations in iron regulatory proteins (IRP) such as IRP-1 and IRP
      2, the main control elements of cellular iron homeostasis. Here, we report that
      while IRP-1 is present at similar levels in both Alzheimer and control brain
      tissue, IRP-2 shows striking differences and is associated with intraneuronal
      lesions, including neurofibrillary tangles, senile plaque neurites and neuropil
      threads. Since IRP-2 colocalizes with redox-active iron, our results suggest that
      alterations in IRP-2 might be directly linked to impaired iron homeostasis in
      Alzheimer's disease.

PMID- 9555031
TI  - Reversible translocation of CTP:phosphocholine cytidylyltransferase from cytosol
      to membranes in the adult bovine liver around parturition.
AB  - The key regulatory enzyme of phosphatidylcholine (PC) synthesis,
      CTP:phosphocholine cytidylyltransferase (CT), is known to be activated in vitro
      by translocation from soluble to particulate fractions of the cell. In the
      present study the periparturient cow was chosen as a model to investigate whether
      translocation of CT can contribute to the regulation of PC synthesis in vivo.
      Between parturition and 1.5 weeks post-partum, the cytosolic CT activity in the
      liver of the adult animal decreased 1.9-fold, and this correlated with a 1.8-fold
      increase in microsomal CT activity. At that time, microsomal CT activity started
      to decline again whereas the cytosolic activity rose concomitantly until both
      activities reached their pre-partum values at 8 weeks post-partum. The activities
      of soluble and membrane-bound CTP:phosphoethanolamine cytidylyltransferase (ET),
      the analogous enzyme in the CDP-ethanolamine pathway, did not change
      significantly throughout this period. Whereas hepatic PC concentrations declined
      until about 2 weeks post-partum and thereafter gradually returned to pre-partum
      levels, the PC levels in very-low-density-lipoproteins, started to rise 2 weeks
      after the partus reaching a maximum of 219% of the original value at 8 weeks post
      partum. These results strongly suggest that there is a reversible redistribution
      of CT between cytosol and membranes in a physiologically relevant animal model,
      supporting the concept that translocation of CT is occurring in vivo.

PMID- 9555032
TI  - SB209670, a potent endothelin receptor antagonist, prevents or delays axonal
      degeneration after spinal cord injury.
AB  - We developed a rat spinal cord transection injury model and investigated whether
      endogenous endothelin takes part in axonal degeneration after injury, by using a
      potent nonselective endothelin receptor antagonist, SB209670. Light microscopic
      analysis showed that axonal degeneration of the spinal cord was clearly observed
      one week after injury, supported by immunohistochemical study with anti
      neurofilament antibody. Electron microscopic observation showed enlargement and
      shrinking of spinal axons in the injured sites one week after injury. Application
      of SB209670 to the lesion sites markedly inhibited axonal damage after injury.
      These results suggest that endogenous endothelin plays a role in axonal
      degeneration after spinal cord injury and that SB209670 prevents or delays the
      axonal degeneration after CNS damage.

PMID- 9555033
TI  - Locus coeruleus neurons from morphine-treated rats do not show opiate-withdrawal
      hyperactivity in vitro.
AB  - In vitro studies have not consistently demonstrated naloxone-precipitated opiate
      withdrawal hyperactivity of locus coeruleus neurons. The reason for this
      inconsistency may be because partial or complete withdrawal occurred during
      preparation of the locus coeruleus slice. The aim of the present study was to
      assay opiate withdrawal-related hyperactivity in neurons recorded from locus
      coeruleus slices while ensuring the maintenance of dependence until naloxone
      precipitated withdrawal. Extracellular recordings were obtained from individual
      locus coeruleus neurons in slices from morphine-treated and drug-naive rats.
      Morphine 1 microM was present in all solutions during preparation and recording
      in slices from morphine-treated rats. The average firing rate of the drug-naive
      controls was 0.93 Hz (+/-0.04 Hz). Bath application of morphine (1 microM) almost
      completely suppressed firing in drug-naive controls (0.058 Hz, +/-0.04 Hz, n=12),
      whereas in solutions containing 1 microM morphine, the firing rate of cells from
      morphine-treated rats averaged 0.71 Hz (+/-0.05 Hz), indicating considerable, but
      incomplete tolerance. In the same slices, naloxone increased the average
      spontaneous firing of locus coeruleus cells to 0.96 Hz (+/-0. 04 Hz). Thus,
      naloxone did not produce withdrawal hyperactivity, but returned the cells from
      morphine-treated rats to control rates. We conclude that locus coeruleus cells in
      locus coeruleus slice preparations from morphine-treated rats did not demonstrate
      withdrawal-related hyperactivity even when dependence was maintained until
      naloxone-precipitated withdrawal. Thus, our results do not support a role for
      adaptations intrinsic to locus coeruleus neurons in withdrawal hyperexcitability,
      but instead imply the necessity of functional afferent activity.

PMID- 9555034
TI  - Local renin-angiotensin system in the pineal gland.
AB  - Besides the classical endocrine renin-angiotensin system (RAS), a local RAS has
      been described also in the brain. We attempted to clarify the existence of a
      local RAS in the pineal gland. Through the use of a ribonuclease protection
      assay, it proved possible to detect the mRNA for angiotensinogen (AOGEN), for the
      angiotensin receptor type 1A (AT1a) and 1B (AT1b) and for the angiotensin
      converting enzyme (ACE) in pineal glands from rats. Renin mRNA, however, could
      not be found by this method. By in situ hybridization and immunocytochemistry,
      AOGEN mRNA was co-localized with the astrocyte marker glial fibrillary acidic
      protein. AT1b mRNA expression exceeded the expression of AT1a mRNA and was co
      localized with the pinealocyte-specific tryptophan hydroxylase. Thus, in the
      mammalian pineal gland there is a local formation of the components of the RAS.
      The presence of angiotensin II receptors further substantiates a role for
      angiotensins and the pineal RAS in the physiology of this gland.

PMID- 9555035
TI  - Effects of toxic doses of methamphetamine (METH) on dopamine D1 receptors in the
      mouse brain.
AB  - Methamphetamine (METH) is a drug of abuse that causes marked DA depletion in the
      mammalian dopaminergic systems. These are characterized by marked decreases in
      presynaptic markers including dopamine (DA) levels and DA transporters. Very
      little research has been carried out to evaluate possible postsynaptic effects of
      this drug. In the present study, we assessed the status of METH on striatal DA D1
      receptors labeled with [3H]SCH23390 after toxic doses of METH that were shown to
      cause marked depletion of various markers of presynaptic DA systems in mice [J.
      Neurochem. 69 (1997) 780]. Our results show that these doses of METH caused 30%
      decrease in striatal DA D1 receptors. In contrast, p53 knockout mice that show
      protection against the toxic effects of METH show no significant decreases in DA
      D1 receptors. These results suggest that toxic doses of METH that cause loss of
      presynaptic DA markers might also affect postsynaptic elements. We discuss the
      possibility that these changes might be secondary to toxic effects of METH on
      intrinsic striatal cell bodies.

PMID- 9555036
TI  - Thyroxine stimulates the acylation of lysophosphatidylethanolamine in rat heart.
AB  - The acylation of cardiac lysophosphatidylethanolamine (LPE) was examined in rats
      treated with thyroid hormone. Rats were treated for five consecutive days with
      thyroxine (250 microg/kg) and controls were treated with saline. On the sixth day
      after an overnight fast, the hearts were removed and perfused in the Langendorff
      mode with 0.1 mM [1-14C]oleic acid. Radioactivity incorporated into
      phosphatidylethanolamine (PE) was increased 1.5-fold (P < 0.025) compared to
      controls. Radioactivity incorporated into phosphatidylcholine was not effected.
      The pool size of phosphatidylethanolamine and de novo biosynthesis of this
      phospholipid from [3H(G)]serine or [1,2-14C]ethanolamine were unaltered by
      thyroxine treatment. Treatment of rats with thyroxine resulted in a 1.5-fold (P <
      0.025) increase in the relative percent of oleic acid in cardiac
      phosphatidylethanolamine. Thyroxine treatment resulted in a 1.8-fold (P < 0.025)
      increase in cardiac microsomal acyl-coenzyme A:1-acyl
      glycerophosphorylethanolamine acyltransferase activity compared to controls
      whereas, phospholipase A, acyl-coenzyme A hydrolase and fatty acyl-coenzyme A
      synthase activities were unaltered. The results demonstrate that the reacylation
      of cardiac LPE is regulated by thyroid hormone.

PMID- 9555037
TI  - Evidence for Fos involvement in the regulation of proenkephalin and prodynorphin
      gene expression in the rat hippocampus.
AB  - For a long time Fos has been proposed to play some role in regulation of the
      proenkephalin (PENK) and prodynorphin (PDYN) gene expression. In recent years,
      however, evidence has accumulated that the transcription of both genes in several
      brain regions in vivo is transactivated by the transcription factor CREB rather
      than by Fos. In the present study, involvement of Fos in the mechanism of the
      PENK and PDYN gene induction in the hippocampal dentate gyrus during seizures
      elicited by kainic acid was studied using a knock-down technique. Pretreatment
      with an antisense oligonucleotide complementary to c-fos mRNA did not influence
      the kainic acid-elicited convulsions. It inhibited, by about 50%, the induction
      of Fos protein in the dentate gyrus during seizures. The subsequent induction of
      PENK and PDYN mRNAs was reduced by more than 60% by the c-fos antisense
      oligonucleotide, while constitutive expression of three other genes (alpha
      tubulin, NMDA receptor-1, and GS protein alpha-subunit) was not affected. The
      obtained results support the view that Fos may be involved in regulation of the
      PENK and PDYN gene expression in the dentate gyrus during seizures, which further
      suggests that the mechanisms triggering the up-regulation of both these genes in
      the dentate gyrus may differ from these working in other brain regions, such as
      the striatum and hypothalamus.

PMID- 9555038
TI  - Cyclosporine A modulation of Ca++ activated K+ channels in cardiac sensory
      afferent neurons.
AB  - Whole-cell and single channel recordings were used to characterize the effects of
      the immunosuppressant cyclosporine A (CsA) on cardiac sensory neurons (CSN) of
      the nodose ganglia. Application of 10 nM CsA resulted in a 29.1% decrease in CSN
      input resistance and an average -8+/-3 mV hyperpolarization of membrane
      potential. Application of 10 nM CsA had no effect on evoked Ca++ currents but
      increased evoked K+ currents by 158.9+/-24%. Application of 10 nM CsA
      significantly increased the open probability of KCa channels by 183+/-9%. These
      results suggest that application of CsA results in the activation of KCa channels
      in cardiac sensory neurons and this effect may contribute to the cellular
      mechanisms underlying CsA modulation of vagal afferent neurons.

PMID- 9555039
TI  - GABAB receptors in the dorsomedial hypothalamus and heart rate in anesthetized
      rats.
AB  - Previous studies have shown that: (1) activation of neurons in the dorsomedial
      hypothalamus (DMH) of the rat by blockade of local GABAA receptors with
      bicuculline methiodide (BMI) elicits cardiovascular changes resembling those seen
      in experimental stress, including marked sympathetically-mediated tachycardia,
      and (2) inhibition of neurons in the same region by local microinjection of the
      GABAA receptor agonist muscimol can virtually abolish stress-induced tachycardia.
      This study examined the possibility that GABAB receptors exist in the neural
      circuitry of the DMH, and that stimulation of these receptors might suppress the
      cardiovascular response to local disinhibition with BMI. Microinjection of BMI 10
      pmol into the DMH in urethane-anesthetized rats resulted in marked tachycardia
      with little or no effect on arterial pressure. Simultaneous injection of the
      GABAB receptor agonist baclofen at doses of 2.5, 5.0 and 10 pmol produced dose
      related suppression of BMI induced tachycardia. Coinjection of the GABAB receptor
      antagonist 2-hydroxysaclofen 100 or 200 pmol had no significant effect on the
      heart rate response to BMI, but reversed the suppression elicited in the presence
      of baclofen. These findings indicate that (1) functional GABAB receptors exist in
      the DMH, and (2) stimulation of these receptors inhibits the tachycardia
      resulting from blockade of local GABAA receptors.

PMID- 9555040
TI  - Ionophore A23187-induced leukotriene biosynthesis in equine granulocytes
      neutrophils, but not eosinophils require exogenous arachidonic acid.
AB  - Equine granulocyte suspensions, mainly consisting of neutrophils, failed to
      produce detectable amounts of leukotrienes when stimulated with calcium ionophore
      A23187 alone, whereas leukotrienes were dose-dependently formed in control
      incubations with human granulocytes. In contrast, ionophore A23187 initiated
      synthesis of leukotrienes B4 and C4 in equine granulocytes when added in
      combination with low concentrations of exogenous arachidonic acid. Similarly,
      ionophore A23187 provoked leukotriene biosynthesis when added alone to human
      whole blood, whereas addition of exogenous arachidonic acid was a prerequisite
      for ionophore A23187-induced leukotriene formation in equine whole blood.
      Leukotriene biosynthesis was provoked by A23187 alone after addition of
      homologous platelets to equine granulocyte suspensions. After separation of
      equine neutrophils and eosinophils, purified eosinophil suspensions produced LTC4
      after stimulation with ionophore A23187 alone, whereas exogenous arachidonic acid
      was required for ionophore-induced LTB4 formation in purified neutrophil
      suspensions. Leukotriene synthesis in both eosinophils and neutrophils was
      suppressed by the 5-lipoxygenase activating protein (FLAP) inhibitor, MK-886.
      Exogenous arachidonic acid was needed for ionophore-induced leukotriene synthesis
      also in bovine granulocytes, but was not a prerequisite for the production of
      leukotrienes in porcine granulocytes or in rat and rabbit white blood cell
      suspensions. The results indicate differences in the mechanisms regulating
      leukotriene synthesis in equine neutrophils, as compared to human granulocytes or
      equine eosinophils, and suggest that elevation of intracellular calcium is an
      insufficient stimulus to provoke utilisation of endogenous arachidonic acid for
      leukotriene synthesis in equine neutrophils.

PMID- 9555041
TI  - Alterations of substance P immunoreactivity in lumbar and thoracic segments of
      rat spinal cord in ultraviolet irradiation induced hyperalgesia of the hindpaw.
AB  - Substance P immunostaining was quantified on sections from the 4th-5th lumbar and
      midthoracic spinal segments of rats at the peak of hyperalgesia following
      ultraviolet irradiation-induced inflammation of one hindpaw. The area of the
      immunostaining in the lumbar dorsal horn was significantly decreased on both
      sides by 50%, while in the thoracic spinal cord, it was increased by 18% on the
      contralateral and stayed unchanged on the ipsilateral side.

PMID- 9555042
TI  - Immunological assessment of the distribution of type VII adenylyl cyclase in
      brain.
AB  - The localization of the nine identified isoforms of adenylyl cyclase in brain has
      been largely based on determination of patterns of mRNA expression. A polyclonal
      antibody has now been developed that specifically recognizes Type VII adenylyl
      cyclase. This antibody was used for immunocytochemical analysis of the
      distribution of Type VII adenylyl cyclase in rat brain. Labeling of Type VII
      adenylyl cyclase was observed in several areas, including cerebellum, caudate
      putamen, nucleus accumbens, hippocampus and cerebral cortex. In some of these
      areas, the staining of the adenylyl cyclase protein suggested the possibility of
      presynaptic localization. For example, in situ hybridization showed Type VII
      adenylyl cyclase mRNA concentrated in cerebellar granule neurons. The cerebellar
      granule cell layer, however, showed little immunostaining, while punctate
      immunostaining was observed in the molecular layer. These results suggested that
      protein synthesized in the granule neurons may be targeted to the neuron
      terminals. Punctate staining in the caudate-putamen, globus pallidus and nucleus
      accumbens also suggested the possibility of axonal and/or dendritic localization
      of Type VII adenylyl cyclase in these regions. Labeling of the soma of cerebellar
      Purkinje cells, cortical pyramidal and non-pyramidal cells and interneurons in
      the cerebellum and hippocampus was also observed. Type VII adenylyl cyclase, like
      the other adenylyl cyclase isoforms, has distinct regulatory characteristics,
      including sensitivity to stimulation by Gsalpha and G protein betagamma subunits,
      modulation by protein kinase C, and high sensitivity to stimulation by ethanol.
      These characteristics, and the discrete localization of this enzyme, may
      contribute to its ability to provide signal integration and/or control of
      neurotransmitter release in particular neurons or brain areas.

PMID- 9555043
TI  - Neuroprotective effects of 2,4-dimethoxybenzylidene anabaseine (DMXB) and
      tetrahydroaminoacridine (THA) in neocortices of nucleus basalis lesioned rats.
AB  - The nicotinic alpha7 agonist dimethoxybenzilidene anabaseine (DMXB) and
      cholinesterase inhibitor tetrahydroaminoacridine (THA) were investigated in a
      trans-synaptic model for neocortical atrophy and degeneration following nucleus
      basalis lesions. Bilateral lesions reduced parietal neuronal density in layers II
      V 8 months later. DMXB administered i.p. daily to rats for 3 months attenuated
      this loss in layers II-V at a 1 mg/kg i.p. dose. A lower, 0.2 mg/kg i.p. dose,
      was neuroprotective in layer IV only. THA (1 mg/kg i.p.) also protected against
      neocortical Nissl-staining deficits.

PMID- 9555044
TI  - Expression of the amino acid dimorphism in the small myelin-associated
      glycoprotein cytoplasmic domain in rat peripheral nerves during postnatal
      development.
AB  - The myelin-associated glycoprotein (MAG) is one of the proteins expressed during
      the period of myelin formation and is believed to play a major role in the
      initiation of myelination. It exists as two differentially expressed isoforms, L-
      and S-MAG, that are generated by alternative mRNA splicing. A nucleotide
      dimorphism at the mRNA level resulting in an Arg/Pro dimorphism in the
      cytoplasmic tail of the S-MAG protein has previously been detected in the rat
      brain. In this study, we show that this dimorphism is detectable in the rat
      peripheral nervous system. We propose an allelic origin for the dimorphism and
      demonstrate the differential expression of the S-MAG alleles in the sciatic
      nerves of heterozygous rats during the period of active myelination. We also
      present data on the properties of the two S-MAG cytoplasmic domains produced as
      GST fusion proteins. The importance of this differentially expressed amino acid
      dimorphism is discussed, taking into account both its probable effect on the S
      MAG cytoplasmic domain function and its significance in functional and structural
      studies concerning the S-MAG protein.

PMID- 9555045
TI  - Single-channel activity of the Ca2+-dependent K+ channel is modulated by FK506
      and rapamycin.
AB  - Single-channel patch clamp recordings were performed in primary cultured neurons
      from rat dorsal hippocampi. Ca2+-dependent and TEA-sensitive K+ current was
      recorded from the neurons. Application of immunosuppressants FK506 and rapamycin
      to the channel inside the plasma membrane of the neurons significantly prolonged
      the mean open time of the channel. Calcineurin autoinhibitory fragment and W-7
      induced no significant alteration in the mean open time of the channel. These
      results suggest that modulation of the activity of the Ca2+-dependent K+ channel
      by FK506 and rapamycin is directly through association of immunosuppressants with
      FKBP12.

PMID- 9555046
TI  - T-->G or T-->A mutation introduced in the branchpoint consensus sequence of
      intron 4 of lecithin:cholesterol acyltransferase (LCAT) gene: intron retention
      causing LCAT deficiency.
AB  - Previous mutations associated with lecithin:cholesteryl acyltransferase (LCAT)
      deficiency syndromes have been identified in the coding regions of the LCAT gene.
      However, recently, an intron mutation was found in a family in which three
      sisters presented with fish-eye disease (FED). The probands were shown to be
      heterozygotes for a mutation in intron 4. The respective T-->C nucleotide
      substitution, 22 bases upstream of the 3'-splice site, causes a null allele as
      the result of complete intron retention. Since the natural mutation occurs in a
      putative branchpoint consensus sequence of the intron, it was hypothesized that
      the point mutation may disrupt the splicing of the pre-mRNA. To further study the
      functional significance of the above thymine residue in the branchpoint sequence,
      we introduced other nucleotides at this position, i.e., LCAT Int-4 MUT-1 (T-->G)
      and LCAT Int-4 MUT-2 (T-->A). After stable transfection of the mutated pNUT-LCAT
      minigenes into BHK cells, we could detect neither LCAT activity nor LCAT protein
      in the culture medium of the pNUT-LCAT Int-4 MUT-1 and pNUT-LCAT Int-4 MUT-2 cell
      lines, as was previously described for the natural mutation. To determine the
      effects of the introduced mutations on pre-mRNA splicing, total RNA from
      transfected BHK cells was used for RT-PCR analysis. All BHK cell lines were shown
      to transcribe the integrated LCAT minigenes. However, the sizes of these LCAT
      messengers indicated that intron 4 was retained in the pNUT-LCAT Int-4 MUT-1 and
      pNUT-LCAT Int-4 MUT-2 cell lines. Subsequent sequence analysis of the RT-PCR
      products demonstrated that the unspliced intronic sequences contained the
      introduced mutations. In conclusion, the observed retention of intron 4 of the
      LCAT gene is the result of the specific loss of a thymine residue two bases
      upstream of the branchpoint adenosine residue in the putative branchpoint
      consensus sequence. The results confirm that a single base change in the
      branchpoint consensus sequence of an intron can cause human disease although this
      sequence is poorly conserved in mammals.

PMID- 9555047
TI  - Distribution of substance P receptor binding in dorsal column nuclei of rat, cat,
      monkey and human.
AB  - In the present study, substance P receptor binding was localized in the dorsal
      column nuclei (DCN) of the rat, cat, monkey, and human. Bolton-Hunter-labeled
      [125I]substance P binding was most concentrated in the cell nests of the core
      region, but was present throughout the DCN of each species. The distribution of
      substance P receptors may reconcile apparent mismatches between the widespread
      responsiveness of DCN neurons to substance P and the restricted distribution of
      substance P containing afferents.

PMID- 9555049
TI  - Electrophysiology of the neuromuscular junction of the laminin-2 (merosin)
      deficient C57 BL/6J dy2J/dy2J dystrophic mouse.
AB  - The C57 BL/6J dy2J/dy2J dystrophic mouse expresses an abnormal truncated form of
      the alpha2 subunit of the protein laminin-2 (or merosin), which is unable to form
      a stable link between the extracellular matrix and the dystrophin-associated
      proteins, resulting in muscular dystrophy. Morphological abnormalities of the
      peripheral nervous system and neuromuscular junction have also been reported. The
      electrophysiological properties of the neuromuscular junctions of diaphragm,
      extensor digitorum longus (EDL), and soleus from C57 BL/6J dy2J/dy2J mice and
      controls are described. No evidence for the presence of denervated fibres were
      found. Mean MEPP amplitudes were significantly increased in EDL and soleus but
      reduced in the diaphragm from affected mice. Mean MEPP frequencies were raised in
      all the dy2J/dy2J muscles studied. dy2J/dy2J muscles were paralysed by low
      concentrations of mu-conotoxin suggesting that embryonic (tetrodotoxin and mu
      conotoxin resistant) sodium channels are not widespread on dy2J/dy2J muscle as
      has previously been reported. EPP latencies were significantly prolonged in the
      diaphragm and EDL but not soleus from dy2J/dy2J mice. Quantal contents were
      higher in all dy2J/dy2J muscles. In the dy2J/dy2J diaphragm failures in
      neurotransmission occurred and a faster rate of rundown of EPPs were apparent.
      Some changes appear from a direct effect of dystrophy, whilst increased MEPP
      frequency and quantal content, and failures in neurotransmission indicate
      neuronal abnormalities.

PMID- 9555048
TI  - Metabotropic glutamate receptor agonist increases neuropeptide mRNA expression in
      rat striatum.
AB  - Metabotropic glutamate receptors (mGluR) are coupled to multiple intracellular
      second messenger systems through G-proteins and densely expressed by medium spiny
      projection neurons in the rat striatum. Unlike ionotropic glutamate receptors
      which mediate rapid synaptic transmission, mGluRs are important for relatively
      long-lasting modulation of neuronal metabotropic activity, possibly including
      gene expression, in response to cellular stimulation. In this study, the effects
      of acute injection of the selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid (ACPD) on behavior and striatal neuropeptide mRNA expression
      were evaluated in chronically-cannulated rats. Unilateral injection of ACPD into
      the dorsal striatum at doses of 0.8, 4, 20, 100, 500 and 1000 nmol had no
      significant effect on spontaneous behavioral activity. However, intrastriatal
      ACPD (0.8, 4, 20 and 100 nmol) dose-dependently elevated preprodynorphin (PPD),
      substance P (SP) and preproenkephalin (PPE) mRNA expression in the dorsal
      striatum as revealed by quantitative in situ hybridization. PPD/SP mRNAs showed a
      biphasic response to a single injection of ACPD as the expression of these two
      mRNAs was increased at 3 and 6 h, decreased at 11 h, and returned to normal 24 h
      after ACPD administration. PPE induction in the dorsal striatum was significantly
      elevated as early as 2 h and remained even 24 h after ACPD was injected. In
      addition, the PPD and PPE mRNA induction by ACPD was blocked by intrastriatal
      pretreatment with the selective mGluR antagonist, (+)-alpha-methyl-4
      carboxyphenyl-glycine. These data demonstrate a facilitatory regulation of
      constitutive expression of striatonigral PPD/SP, and striatopallidal PPE, mRNAs
      by local mGluR-mediated glutamatergic transmission.

PMID- 9555050
TI  - Comparison of [125I]-bolton-hunter substance P binding in young and aged rat
      spinal cord.
AB  - Binding of [125I]-labeled Bolton-Hunter substance P ([125I]-BHSP) to NK1
      receptors was investigated in the spinal cord of young (3-4 month) and aged (14
      16 month) rats. In homogenates of whole spinal cord, the affinity (equilibrium
      dissociation constant, approximately 210 pM) and maximum density of [125I]-BHSP
      binding sites ( approximately 0.25 fmol/mg wet weight) were similar for young and
      aged rats. Autoradiographic studies revealed a similar distribution of [125I]
      BHSP sites in both young and old rats at all spinal levels. Intense binding was
      observed in the superficial dorsal horn (laminae I-III), grey commissure (lamina
      X) and thoracic intermediolateral cell column (IML) with lower levels of binding
      in the deeper dorsal horn (laminae IV-VI) and ventral horn (laminae VII-IX).
      However, the density of [125I]-BHSP sites was significantly (P<0.05) lower in
      lamina X of lumbar sections of aged rats compared with young controls. These
      studies suggest that ageing is associated with a selective loss of NK1 receptors
      in lamina X of the lumbar spinal cord, although the affinity of NK1 receptors in
      aged rats is unchanged.

PMID- 9555051
TI  - Hexadecylphosphocholine and 2-modified 1,3-diacylglycerols as effectors of
      phospholipase D.
AB  - The kinetic behaviour of phospholipase D (PLD) from cabbage has been studied in
      the presence of several substrate-like compounds such as hexadecylphosphocholine
      (HPC) and 1,3-didodecanoylglycero-2-phosphatides. 1,3-Didodecanoyl- glycero-2
      phosphocholine (1,3-DiC12PC) was found being not cleft by PLD, whereas HPC is
      hydrolyzed by PLD with small rate. The plot of initial velocity vs. substrate
      concentration for HPC is more sigmoidal than those for the common substrate
      phosphatidylcholine (PC)/sodium dodecylsulfate (SDS) (1:0.5) or the short-chain
      1,2-dihexanoyl-sn-glycero-3-phosphocholine (DiC6PC). The anionic amphiphiles 1,3
      didodecanoylglycero-2-sulfate and 1,3-didodecanoylglycero-2-phosphate act as
      activators of PLD towards PC similar to SDS. In contrast, 1,3-DiC12PC shows
      inhibitory properties with an increase in the sigmoidicity of the initial
      velocity as a function of substrate concentration in the PC/SDS assay. Also HPC
      inhibits the hydrolysis of PC/SDS, whereas it acts as activator or inhibitor in
      the hydrolysis of DiC6PC. The results suggest that PLD possesses two substrate
      binding sites, where one binds substrate in function of an effector without
      catalytic activity while the other is the catalytic site. HPC and 1,3-DiC12PC are
      assumed to compete with the substrate for both binding sites with effects
      depending on the ratio of concentrations and affinities of substrates and
      effectors.

PMID- 9555052
TI  - Neuroprotection of mild hypothermia: differential effects.
AB  - To estimate whether mild hypothermia during repetitive hypoxia provides a
      neuroprotective effect on brain tissue, hippocampal slice preparations were
      subjected to repetitive hypoxic episodes under different temperature conditions.
      Slices of guinea pig hippocampus (n=40) were placed at the interface of
      artificial cerebrospinal fluid (aCSF) and gas (normoxia: 95% O2, 5% CO2; hypoxia:
      95% N2, 5% CO2). Evoked potentials (EP) and direct current (DC) potentials were
      recorded from hippocampal CA1 region. Slices were subjected to two repetitive
      hypoxic episodes under the following temperature conditions: (A) 34 degrees C/34
      degrees C, (B) 30 degrees C/30 degrees C and (C) 34 degrees C/30 degrees C.
      Hypoxic phases lasted until an anoxic terminal negativity (ATN) occurred. The
      recovery after first hypoxia lasted 30 min. Tissue function was assessed
      regarding the latency of ATN and the recovery of evoked potentials. The ATN
      latencies with protocol A (n = 25) for the first and second hypoxia were 5.9+/
      1.3 min (mean+/-S.E.M., 1st hypoxia) and 2.4+/-0.9 min (2nd hypoxia), with
      protocol B the latencies (n = 7) were significantly longer: 25.2+/-7.1 min and
      15.6+/-7.7 min. With protocol C (n=8), the latencies were 5.6+/-1.8 and 3.3+/-0.5
      min. No differences were seen in the recovery of the EPs with protocols A-C. Our
      results suggest that a mild hypothermia is only neuroprotective if applied from
      an initial hypoxia onwards.

PMID- 9555053
TI  - Effects of aniracetam after LTP induction are suggestive of interactions on the
      kinetics of the AMPA receptor channel.
AB  - The modulatory influence of aniracetam, a drug which reversibly modifies the
      kinetic properties of AMPA-type glutamate receptors, on synaptic responses is
      reported to be detectably changed by the induction of long-term potentiation
      (LTP). The present study used hippocampal slices to examine three issues arising
      from this result. First, possible contributions of inhibitory currents and
      postsynaptic spiking to the aniracetam/LTP interaction were investigated with
      infusions of GABA receptor antagonists and topical applications of tetrodotoxin.
      Second, tests were carried out to determine if the altered response to aniracetam
      is sufficiently persistent to be a plausible substrate for the extremely stable
      LTP effect. Third, the nature of the change responsible for the aniracetam/LTP
      interaction was explored with waveform analyses and a kinetic model of the AMPA
      receptor. The following results were obtained. LTP reduced the effect of
      aniracetam on the amplitude but increased its effect on the decay time constant
      of field EPSPs recorded under conditions in which local spiking and inhibitory
      responses were blocked. The LTP-induced change in the effect of aniracetam was
      extremely stable in that it was still evident 75 min after induction of
      potentiation. Finally, the waveform distortions introduced by LTP and aniracetam
      could be corrected by uniform stretching of the responses, suggesting that the
      changes introduced by each of the manipulations are unitary in nature. These
      distortions and the interactions between them could be reproduced in the AMPA
      receptor model by representing LTP as an acceleration of channel gating kinetics.

PMID- 9555054
TI  - Vitamin E protects against Alzheimer's amyloid peptide (25-35)-induced changes in
      neocortical synaptosomal membrane lipid structure and composition.

PMID- 9555055
TI  - Caloric restriction retards the aging associated changes in gamma-aminobutyric
      acidA receptor gene expression in rat cerebellum.
AB  - It is widely accepted that calorie restriction is an effective way of delaying
      the aging process. Also, there is an indication that the beneficial effects
      exerted by dietary manipulation may be due to a direct effect at the molecular
      level like gene expression. The studies were conducted to determine whether
      calorie restriction prevents any age-related changes in the structural and
      molecular aspects of the GABAA-BZ receptor. In aged (24-month old diet ad
      libitum) rats, the binding of [35S]t-butyl-bicyclophosphorothionate (TBPS) was
      significantly reduced in the cerebellum. In contrast, [35S]TBPS binding remained
      unchanged in the cerebellum of calorie restricted old rats. In order to evaluate
      the molecular basis of these changes, the alpha sub-unit mRNA levels were
      measured. The GABAA receptor alpha1 sub-unit mRNA level remained unchanged in
      both the old groups of rats. The alpha2 subunit mRNA level was significantly
      decreased in the cerebellum of aged rats (24-month old ad libitum), whereas it
      remained unchanged in the cerebellum of calorie restricted old animals. These
      findings indicate a selective age and diet related modulation in the
      stoichiometry of the GABAA receptor in aging.

PMID- 9555056
TI  - Lipid metabolism in fibroblast growth factor-stimulated L6 myoblasts: a receptor
      mutation (Y766F) abrogates phospholipase D and diacylglycerol kinase activities.
AB  - Phosphatidylcholine (PC) hydrolysis induced by basic fibroblast growth factor
      (bFGF) was studied in rat L6 myoblasts expressing the wild-type FGF receptor-1
      (FGFR-1) or a mutant (Y766F) that is incapable of activating phospholipase C
      gamma (PLCgamma). Stimulation of FGFR-1 activated phospholipase D (PLD) rapidly
      and transiently, but did not induce PC-specific PLC activity. Downregulation of
      protein kinase C blocked bFGF-induced PLD activation but not phosphatidic acid
      formation by diacylglycerol (DG) kinase. Only phosphoinositide (PI)-derived DG,
      not PC-derived DG, appeared to be a substrate for DG kinase. Stimulation of FGFR
      1(Y766F) did not activate PLD or DG kinase, both of which apparently require
      initial PLCgamma activation. The Y766F mutation reduced mitogen-activated protein
      kinase activation but not cell proliferation. We conclude that both PI turnover
      and PC hydrolysis are dispensable for bFGF-induced mitogenesis.

PMID- 9555057
TI  - Molecular heterogeneity of Vicia villosa-recognized perineuronal nets surrounding
      pyramidal and nonpyramidal neurons in the guinea pig cerebral cortex.
AB  - Of three monoclonal antibodies (mAbs Cat 301, 1B5 and 473) which recognize
      epitopes on perineuronal nets (PnNs), only mAb 473 displayed considerably varied
      degrees of staining intensity on Vicia villosa-labeled pyramidal (P) neurons (5%,
      intensely; 54%, very weakly; and 41%, unstained). These results indicate the
      heterogeneity on molecular structure or composition of the terminal N
      acetylgalactosamine-containing PnNs within P class as well as between P and
      nonpyramidal classes.

PMID- 9555059
TI  - A role for phospholipase D activation in the lipid signalling cascade generated
      by bradykinin and thrombin in C2C12 myoblasts.
AB  - In the present study evidence is provided for a rapid activation of lipid
      signalling pathways induced by thrombin and bradykinin (BK) in C2C12 myoblasts.
      Both agonists were able to increase [3H]inositol phosphates (InsP), 1,2
      [3H]diacylglycerol (DAG) and [3H]phosphatidic acid (PtdOH) levels. In particular
      [3H]PtdOH values were rapidly increased and maintained at significantly high
      values at prolonged times of incubation. BK and thrombin were able to activate
      phospholipase D (PLD) in vivo as demonstrated by the accumulation of
      [3H]phosphatidylethanol (PtdEtOH) through the transphoshatidylation reaction
      catalyzed by the enzyme in the presence of ethanol. The observation that ethanol
      could significantly reduce [3H]PtdOH formation in myoblasts stimulated with BK
      and thrombin indicates that stimulation of PLD has a major role. The two agonists
      appear to stimulate PLD activity through a common molecular mechanism, involving
      the activation of protein kinase C (PKC). In addition, BK and thrombin appear
      able to activate DAG kinase at early times of incubation and also this pathway
      may contribute to determine the increase in [3H]PtdOH levels. This is the first
      report which describes activation of lipid signalling pathways by BK and thrombin
      in myoblast cells and it is possible that these early signals may have an
      important role in mediating the biological effects of the two agonists.

PMID- 9555058
TI  - Abnormal properties of creatine kinase in Alzheimer's disease brain: correlation
      of reduced enzyme activity and active site photolabeling with aberrant cytosol
      membrane partitioning.
AB  - The report shows that Alzheimer's disease (AD) brain creatine kinase (CK) is
      modified such that the nucleotide binding site of CK is blocked and that abnormal
      partitioning of CK between the soluble and pellet fractions occurs. First, CK
      activity was 86% decreased in AD brain homogenates in comparison to age-matched
      controls. Secondly, over a 23.5 fold greater 32P photoincorporation of [alpha
      32P]8N3ATP was observed into CK of control vs. AD samples. Also, a 7.4-fold
      increase of enzyme induced 32P incorporation was observed in controls vs. AD
      samples by incubation with [gamma 32P]ATP. Thirdly, Western blot analysis showed
      that CK copy numbers in the AD homogenate were decreased by less than 14% in
      comparison to controls. However, analysis showed that control supernatant and
      pellet fractions contained 10.3 and 0.4 times the CK copy number found in the
      corresponding AD fractions. 32P incorporation by both photolabeling and enzyme
      catalyzed incorporation of radiolabel followed CK activity and not CK copy
      number. Further, [alpha 32P]ADP and [gamma 32P]ATP incorporated 32P into control
      brain and purified brain CK equally well, indicating that a mechanism different
      from gamma-phosphoryl transfer is involved in the enzymatic incorporation of
      radiolabel. Also, the level of abnormal partitioning of CK into AD brain pellet
      correlated with the decreased [32P]8N3GTP photolabeling and abnormal partitioning
      of beta-tubulin, a protein known to be aberrantly modified in the AD brain. This
      indicates that a common chemistry is affecting both CK and tubulin in AD.

PMID- 9555060
TI  - Role of noradrenergic projections to the bed nucleus of the stria terminalis in
      neuroendocrine and behavioral responses to fear-related stimuli in rats.
AB  - The bed nucleus of the stria terminalis (BNST) receives dense noradrenergic
      projections from the brainstem and has been claimed to play a role in expression
      of a variety of stress responses. Fear-related stimuli suppress vasopressin and
      facilitate oxytocin release from the neurohypophysis and induce behavioral
      suppression. Here we investigated in male rats whether conditioned fear stimuli
      increase noradrenergic activity in the BNST and whether depletion of epinephrine
      content in the BNST prevents neuroendocrine and behavioral responses to fear
      stimuli. Environmental stimuli previously paired with electric footshocks
      increased the ratio of 3-methoxy-4-hydroxyphenylglycol to norepinephrine contents
      in the BNST, suggesting that the stimuli activated noradrenergic projections to
      the BNST. 5-Amino-2, 4-dihydroxy-alpha-methylphenylethylamine, a neurotoxin
      relatively selective for noradrenergic fibers, when injected into the BNST 7 days
      before measurement, decreased the content of norepinephrine by 95% and that of
      dopamine or serotonin by about 50%. In the rats that received the neurotoxin, the
      suppressive vasopressin but not the augmentative oxytocin response to
      intermittent footshocks was abolished. In the experiments with conditioned fear
      stimuli, the neurotoxin given before training partially but significantly
      impaired the suppressive vasopressin and behavioral responses to testing stimuli.
      The neurotoxin given after training, however, did not prevent the vasopressin,
      oxytocin or behavioral responses. The results suggest that noradrenergic fibers
      in the BNST mediate the suppressive vasopressin but not the augmentative oxytocin
      response to nonassociatively applied fear stimuli and that they modulate, in a
      facilitative fashion, acquisition but not retention or recall of the emotional
      memory associated with the vasopressin and behavioral responses to conditioned
      fear stimuli.

PMID- 9555061
TI  - Physiological properties and functions of intracellular fatty acid-binding
      proteins.

PMID- 9555062
TI  - The stimulation of rat astrocytes with phorbol-12-myristate-13-acetate increases
      the proenkephalin mRNA: involvement of proto-oncogenes.
AB  - The effect of phorbol-12-myristate-13-acetate (PMA) on the regulation of
      proenkephalin (proENK) mRNA level, ENKCRE-2 or AP-1 DNA binding activity, and the
      mRNA and protein levels of proto-oncogenes (c-fos, fra-1, and c-jun) in primary
      cultured rat astrocytes were studied. The proENK mRNA level was elevated at 4 h
      after the treatment of PMA (2.5 microM) without altering the intracellular proENK
      protein level, and this increase was attenuated by pre-treatment with
      cycloheximide (CHX; 15 microM), a protein synthesis inhibitor. Both AP-1 and
      ENKCRE-2 DNA binding activities were markedly increased at 1-4 h by PMA treatment
      and these PMA-induced responses were inhibited by pre-treatment with CHX, showing
      that the increase of proENK mRNA level was well correlated with the AP-1 and
      ENKCRE-2 DNA binding activities. In contrast, although the phospho-CREBP level
      was also increased by PMA at 0.5-1 h, the pre-treatment with CHX further
      increased the PMA-induced phospho-CREBP level. In addition, PMA caused the
      induction of c-fos, c-jun and fra-1 mRNA level and, especially, PMA-induced
      increase of fra-1 mRNA level was further enhanced by CHX treatment at 4 h.
      Furthermore, western immunoblot assay showed that PMA caused induction of c-Fos,
      Fra-1, and c-Jun protein levels. PMA-induced increases of proto-oncoproteins
      levels were also inhibited by CHX treatment. The results suggest that newly
      synthesized AP-1 proteins, such as c-Fos, Fra-1, and c-Jun may play important
      roles in the regulation of PMA-induced proENK gene expression in cultured rat
      astrocytes. Phospho-CREB protein appears not to be involved in the regulation of
      PMA-induced proENK gene expression.

PMID- 9555063
TI  - Dopamine levels of two classes of vesicles are differentially depleted by
      amphetamine.
AB  - Differential depletion of neurotransmitter by amphetamine in two classes of
      vesicles, termed large vesicles and small vesicles, has been studied with
      amperometry. Carbon fiber microelectrodes have been used to monitor and quantify
      exocytotic events. Current transients, corresponding to individual exocytotic
      events, have been obtained from the cell body of the dopamine-containing neuron
      of Planorbis corneus. The dopamine released from individual vesicles of these
      cells has been compared for cells treated with D-amphetamine vs. control cells.
      Our results show that amphetamine has differential effects on the release of
      dopamine from the two classes of vesicles. Thus, it is concluded that at low
      concentrations, amphetamine preferentially depletes the large vesicles with a
      minimal effect on the small vesicles. At high concentrations, amphetamine
      depletes small vesicles more strongly than large vesicles although amphetamine
      continues to deplete the large vesicles in a dose-dependent manner. Our data
      appear to indicate that the two classes of vesicles observed in the Planorbis
      dopamine neuron might have different mechanisms associated with transmitter
      depletion.

PMID- 9555064
TI  - Differential catalytic properties in metabolism of endogenous and exogenous
      substrates among CYP3A enzymes expressed in COS-7 cells.
AB  - The catalytic properties of CYP3A7 in the metabolism of endogenous and exogenous
      substrates were compared with those of CYP3A4 and CYP3A5 using COS-7 expressing
      enzymes. The highest activities of dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone 3-sulfate (DHEA-S) 16alpha-hydroxylase were observed in
      COS-7 cells expressing CYP3A7. In contrast, the activity of testosterone 6beta
      hydroxylase of CYP3A7 expressed in COS-7 cells was much less than that of CYP3A4
      expressed in COS-7 cells. The rate of carbamazepine 10, 11-epoxidation was the
      greatest in COS-7 cells expressing CYP3A4, followed by CYP3A5 and CYP3A7. On the
      other hand, the formation of reductive metabolite of zonisamide was the highest
      in COS-7 cells expressing CYP3A4, followed by CYP3A7 and CYP3A5. Furthermore, the
      addition of triazolam resulted in a decrease in 6beta-hydroxylation catalyzed by
      CYP3A7, but not by CYP3A4, whereas the pretreatment of microsomes with
      triacetyloleandomycin (TAO) resulted in a decrease in the reaction catalyzed by
      CYP3A4, but not by CYP3A7. Together with these results, it was suggested that
      CYP3A7 exerts differential catalytic properties not only in metabolism of
      endogenous substrates but also in drug metabolism compared to CYP3A4 and CYP3A5.

PMID- 9555065
TI  - Differential localization of the mRNAs for the pertussis toxin insensitive G
      protein alpha sub-units Gq, G11, and Gz in the rat brain, and regulation of their
      expression after striatal deafferentation.
AB  - The corticostriatal pathway is among the largest glutamatergic pathways in the
      brain, and of particular interest to the study of glutamatergic transmission. The
      metabotropic glutamate receptors (mGluRs) couple the actions of glutamate to
      intracellular second messenger systems through G-proteins. The most prominent of
      the mGluRs present in the target of this pathway, the striatum, is mGluR5. The
      identity of the G-proteins mediating the actions of mGluR5 are unknown, but the
      receptor is linked to stimulation of phosphoinositide (PI) turnover and largely
      resistant to the effects of pertussis toxin, which inhibits some G-proteins. We
      used in situ hybridization to examine the expression and regulation of three
      pertussis toxin insensitive G-protein alpha sub-units: Gq, G11, and Gz. We found
      that these mRNAs are differentially distributed in the rat brain, but all three
      are expressed by striatal neurons. After glutamatergic deafferentation of the
      striatum by decortication, there is a modest upregulation of G11 mRNA, while
      expression of Gq and Gz are unchanged. Following dopaminergic deafferentation,
      expression of Gq, G11, and Gz are not altered, although expression of the
      pertussis-sensitive sub-unit Go is increased. Our data suggests that Gz, Gq, and
      G11 are each expressed by striatal neurons, and therefore may be involved in
      mediating the actions of mGluR5 in these cells. After decortication G11 is
      upregulated, but the magnitude of this effect is small, and alone seems
      insufficient to account for the marked biochemical supersensitivity of glutamate
      stimulated PI turnover which is observed.

PMID- 9555066
TI  - Effect of hyperglycemia on pyruvate dehydrogenase activity and energy metabolites
      during ischemia and reperfusion in gerbil brain.
AB  - The effects of hyperglycemia on brain pyruvate dehydrogenase (PDH) and
      metabolites (ATP, PCr, and lactate) were investigated at 20 min ischemia, 0, 20,
      and 60 min, and 4 h reperfusion. During reperfusion, PDH activities were
      suppressed corresponding to the poor recovery of ATP and PCr concentrations and
      the increase in lactate concentration in the hyperglycemic group, suggesting that
      preischemic hyperglycemia may impair metabolism by suppressing PDH activity.

PMID- 9555067
TI  - Rapid stress-induced elevations in corticotropin-releasing hormone mRNA in rat
      central amygdala nucleus and hypothalamic paraventricular nucleus: an in situ
      hybridization analysis.
AB  - High densities of nerve cells containing corticotropin-releasing hormone (CRH)
      are located in the central nucleus of the amygdala (CeA) and paraventricular
      nucleus (PVN) of the hypothalamus. These brain regions play an important role in
      activating autonomic, behavioral, and endocrine responses to stress. This study
      was conducted to provide needed information concerning the acute effects of
      stress on CeA and PVN CRH mRNA expression. Rats were exposed to restraint stress
      for 1 h and brains collected after a 1-h post-stress interval. CRH mRNA
      expression occurring in the CeA and PVN was examined using in situ hybridization
      techniques. Densitometric analysis revealed that acute restraint stress produced
      significant increases in CRH mRNA levels in the PVN and in the rostral CeA
      region. In addition, the area in the rostral CeA encompassing high CRH mRNA
      signals increased significantly after stress. Results provide clear evidence that
      CRH neurons in the CeA and PVN exhibit rapid increases in CRH mRNA expression
      after exposure to stress.

PMID- 9555068
TI  - Tissue distributions of CYP2D1, 2D2, 2D3 and 2D4 mRNA in rats detected by RT-PCR.
AB  - The tissue distributions of four isoforms (CYP2D1/5, 2D2, 2D3 and 2D4/18) in rat
      CYP2D subfamily were investigated. Twelve kinds of tissue (liver, kidney, brain,
      lung, heart, spleen, adrenal gland, small intestine mucosa, bladder, testis,
      ovary and gonecystis) were removed from Sprague-Dawley male and female rats. The
      expression of CYP2D mRNA in these tissues was detected by RT-PCR. Specific
      primers were designed to recognize the four isoforms individually. In liver,
      kidney and small intestine mucosa, the mRNA expression of all four CYP2D isoforms
      was detected as high-intensity PCR products. mRNA of CYP2D1/5 was expressed in
      all tissues used in this study except the brain, although the intensity of PCR
      products varied among tissues. mRNAs of CYP2D2 and CYP2D3 were mainly expressed
      in liver, kidney and small intestine mucosa, which were exposed to xenobiotics
      such as drugs, food components and environmental contaminations. mRNA of
      CYP2D4/18 was expressed in liver, kidney, small intestine mucosa and brain. In
      brain, only mRNA of CYP2D4/18 was expressed. CYP2D4/18 mRNA was also expressed in
      ovary, testis and gonecystis. The tissue distributions help to clarify the
      differences in physiological and pharmacological functions between CYP2D
      isoforms.

PMID- 9555069
TI  - Studies on the regulation of CTP:phosphocholine cytidylyltransferase using
      permeabilized HEP G2 cells: evidence that both active and inactive enzyme are
      membrane-bound.
AB  - To obtain more insight into the mechanisms regulating CTP:phosphocholine
      cytidylyltransferase (CT), we determined the effect of oleate treatment on the
      rate of CT release from permeabilized Hep G2 cells and the distribution of the CT
      remaining in the permeabilized cells. When we permeabilized untreated cells in pH
      7.5 buffer containing 0.15 M KCl, the rate of CT release was much slower than the
      release of lactate dehydrogenase. Oleate treatment caused a further decrease in
      CT release from cells. In untreated cells, 70-80% of the CT remaining in cells 10
      min after permeabilization was recovered as soluble CT. Oleate treatment
      increased the amount of bound CT but over 50% of the CT in cells 10 min after
      permeabilization was recovered as soluble CT. In both control and oleate-treated
      cells, the increase in CT release with time correlated with a decrease in the
      amount of CT recovered from permeabilized cells as soluble CT. These results
      suggested that CT existed in a form that was not immediately available for
      release from permeabilized cells, but was recovered in the soluble fraction after
      cell disruption. When cells were permeabilized in 10 mM imidazole-20% glycerol-5
      mM Mg2+ pH 6.5, over 80% of CT in control and over 90% of CT in oleate-treated
      cells was recovered bound to the particulate fraction. Essentially no CT was
      released from the cells. The recovery of CT in the particulate fraction required
      Mg2+ to be present when permeabilization was initiated. The addition of Mg2+,
      after cells were disrupted, did not increase CT in the particulate fraction. In
      untreated cells, 50% of bound CT was active. Oleate treatment increased the
      amount of active CT in the particulate fraction to over 70% of total. About 50%
      of particulate CT in untreated cells but only 15% in oleate-treated cells was
      extracted with 0.15 M KCl. Inactive CT was preferentially extracted by KCl. The
      bound CT was recovered in isolated nuclei. Overall, the results suggested that
      both inactive and active CT are bound to nuclear membranes, and that the
      activation of CT involves conversion of CT loosely bound to membrane to a form
      more tightly bound to membranes perhaps by hydrophobic interaction with
      phospholipids. This model does not involve translocation from a soluble pool.

PMID- 9555070
TI  - Changes in presynaptic protein NACP/alpha-synuclein in an ischemic gerbil
      hippocampus.
AB  - We observed temporal changes in NACP (precursor protein of non-Abeta component of
      Alzheimer's disease amyloid), a presynaptic protein a.k. a. alpha-synuclein, in
      the hippocampus after 5 min ischemia. Intense NACP immunoreactivity was seen
      transiently around cerebral blood vessels in the CA1 subfield on day 4, and NACP
      positive unusual tubal and chain-like structures developed on month 6. We suggest
      that the changes in NACP may play an important role in the ischemic pathogenesis.

PMID- 9555071
TI  - Localization of the mRNAs for two isoforms of Ca2+/calmodulin-dependent protein
      kinase kinases in the adult rat brain.
AB  - Ca2+/calmodulin-dependent protein kinase (CaM kinase) I and IV are thought to be
      activated by CaM kinase kinases (CaMKK). We examined the distribution of mRNAs
      for two isoforms (alpha and beta) of CaMKKs in the brain by in situ hybridization
      histochemistry. In the adult rat brain, CaMKK alpha mRNAs are widely distributed
      throughout the brain, whereas CaMKK beta mRNAs are restricted to some neuronal
      populations, particularly the cerebellar granule cells.

PMID- 9555072
TI  - Irreversible phase transition of firefly luciferase: contrasting effects of
      volatile anesthetics and myristic acid.
AB  - Firefly luciferase (FFL) has been used as a lipid-free protein model to study
      direct interaction of anesthetics with proteins. FFL emits a burst of light when
      luciferin and ATP are added in the presence of oxygen. Volatile anesthetics
      inhibited FFL at mM ranges, while myristic acid inhibited it at microM range.
      Despite the large difference, octanol/water partition coefficients of both
      myristic acid and halothane are 199. Differential scanning calorimetry (DSC)
      showed that thermal transition occurred at 38.5 degreesC with excess enthalpy of
      denaturation of 91.9 kcal mol-1. The transition, however, was irreversible.
      According to the irreversible transition kinetics, the anesthetic effects were
      evaluated by the temperature where the irreversible transition is half completed
      (T1/2). Volatile anesthetics decreased T1/2 at mM ranges, while myristic acid and
      oxyluciferyladenylate (luciferin competitor) increased it at microM ranges.
      Luciferin is a heterocyclic carboxylate and acylates AMP. Carboxyl group of
      myristic acid appears to make a high affinity contact to the luciferin
      recognition sites. The induced-fit theory states that binding of substrates
      induces the enzyme into high-energy transition state. Myristic acid stabilized
      FFL at the transition state, which resisted thermal denaturation. Anesthetics
      destabilized FFL by reversibly unfolding the protein into less active
      intermediate states and promoted irreversible transition when the temperature is
      elevated.

PMID- 9555073
TI  - Striatal glutamate antagonism induces contralateral neglect.
AB  - To assess the role of striatal glutamatergic synapses in mediating sensorimotor
      orientation behavior, glutamate receptor antagonists were infused into the left
      striatum of awake rats and behavioral orientation to contralateral and
      ipsilateral stimuli were quantified. The AMPA-kainate antagonist, DNQX, and the
      NMDA antagonist, CPP, both induced a large asymmetry in responding, such that the
      rats oriented much less to stimuli presented contralateral to the antagonist
      infusions. Furthermore, intrastriatal glutamate antagonist infusions increased
      the occurrence of incorrect responses, or turning away from a contralaterally
      presented stimulus. In a separate experiment, intrastriatal DNQX was shown to
      block kainic acid (KA)-induced Fos expression in the striatum, but not in
      adjacent cerebral cortex, suggesting that the diffusion of this drug is
      restricted to the striatum.

PMID- 9555074
TI  - Expression pattern of a novel death-promoting gene, DP5, in the developing murine
      nervous system.
AB  - We examined the expression patterns of the DP5 gene, which encodes a protein with
      apoptosis-inducing activity, in the developing nervous system of mice. This gene
      was primarily expressed in the spinal motor neurons and peripheral sensory
      ganglia of mouse embryos and transiently in the postnatal brain, particularly in
      the entorhinal cortex and hippocampus. These expression patterns suggest that the
      DP5 gene may be involved in the apoptosis, if not all, of the developing nervous
      system.

PMID- 9555075
TI  - Proteolytic processing of a secreted glycoprotein and O-glycosylation of
      mannoproteins are affected in the N-glycosylation mutant Saccharomyces cerevisiae
      ldb1.
AB  - In a previous work [P.I. Manas, I. Olivero, M. Avalos, L.M. Hernandez,
      Glycobiology, 7 (1997) 487-497], we described the isolation and characterization
      of the Saccharomyces cerevisiae ldb1 mutant which is affected in several steps of
      the N-glycosylation of mannoproteins probably due to a malfunction of the Golgi
      apparatus. Here, we found that two further functions assigned to the Golgi
      cisternae are also affected in the mutant: proteolytic processing of a secreted
      protein and O-glycosylation. We found that around 70% of the exoglucanase
      activity that is secreted into the culture medium by ldb1 bears an extra
      tetrapeptide in its NH2-terminus due to incomplete proteolytic processing. The O
      linked oligosaccharides from ldb1 mnn1 were indistinguishable from those
      synthesized by the parental strain mnn1. However, when the O-oligosaccharides
      from the wild type and ldb1 were compared, we found a significant decrease in the
      tetrasaccharide in the latter, as well as a concomitant increase in the
      disaccharide, suggesting a defect in the Kre2p/Mnt1p involved in the transfer of
      the third mannose of these residues.

PMID- 9555076
TI  - Expression of estrogen receptor alpha and beta transcripts in female monkey
      hippocampus and hypothalamus.
AB  - Understanding mechanisms of estrogen effects on cognition is critical for
      designing therapies for post-menopausal women and others with dementia.
      Hippocampus, an area important to cognitive function, responds robustly on
      estrogen. ERbeta and ERalpha transcripts were detected in the hippocampus and
      hypothalamus of an ovariectomized female monkey at a relatively high
      ERbeta/ERalpha ratio. These results suggest that ERbeta may play a role in
      mediating estrogen effects in the primate hippocampus and hypothalamus.

PMID- 9555077
TI  - Xanthophyll biosynthesis: molecular and functional characterization of carotenoid
      hydroxylases from pepper fruits (Capsicum annuum L.).
AB  - To dissect the mechanism by which carotenoid hydroxylases catalyze xanthophyll
      formation, we have cloned two pepper cDNAs encoding beta-cryptoxanthin and
      zeaxanthin biosynthetic enzymes. Using an in vitro system, we find that both
      enzymes are ferredoxin dependent and that their activity is strongly inhibited by
      iron chelators such as o-phenanthroline or 8-hydroxyquinoline. This suggests the
      transfer of a reducing equivalent from NADPH to the hydroxylase via ferredoxin
      and the involvement of an iron activated oxygen insertion process. Based on
      sequence analysis, the putative histidine clusters involved in the iron
      coordination were identified and their roles evaluated. Following site-directed
      mutagenesis of the identified histidine residues hydroxylase activity was totally
      inactivated. Collectively, our data indicate that carotenoid hydroxylases belong
      to a new class of diiron proteins structurally related to membrane fatty acid
      desaturases. Mechanistically, both types of enzymes exploit iron activated oxygen
      to break the C-H bond with concomitant formation of double bond or oxygen
      insertion. We propose that the same mechanism operates for beta-carotene ketolase
      and probably for other carotenoid oxygenases as well.

PMID- 9555078
TI  - mu Opioid receptor knockout in mice: effects on ligand-induced analgesia and
      morphine lethality.
AB  - The mu opioid receptor gene (MOR) was mutated in mice by a gene targeting
      procedure. In these MOR-knockout mice, the analgesic effects of morphine, its
      major metabolites, morphine-6-glucuronide (M-6-G) and morphine-6-ethereal sulfate
      (M-6-S), and endomorphin-2, as well as morphine-induced lethality, were
      drastically reduced, whereas the effects of DPDPE and U50488 remained unchanged.
      It is concluded that analgesic effects of mu-specific opioid ligands and acute
      morphine lethality are mediated by the mu receptor.

PMID- 9555079
TI  - Muscarinic-receptor antagonist scopolamine rescues hippocampal neurons from death
      induced by glutamate.
AB  - Cultured hippocampal neurons were used to test the hypothesis that modulation of
      muscarine receptors can modify glutamate-induced neurodegeneration. Treatment of
      hippocampal cultures with scopolamine (1 nM to 1 mM) under glutamate incubation
      had beneficial effect on neuronal viability. Thus, blockade of muscarinic
      receptor sites increased the threshold for glutamate neurotoxicity. These data
      show that interactions between the NMDA, muscarinic receptors and their
      corresponding neurotransmitter inputs to hippocampal neurons may play a crucial
      role in neurodegeneration.

PMID- 9555080
TI  - Polysynaptic neuronal pathways from group I and group II afferents innervating
      tail muscles to hindlimb motoneurons in the cat.
AB  - Postsynaptic potentials evoked in motoneurons innervating m. posterior biceps and
      semitendinosus (PBSt) and m. triceps surae (GS) by low threshold afferents from
      various tail muscles located at the level of the second-third caudal vertebrae
      were investigated in the non-anesthetized and spinalized cat. Afferent inputs
      from tail muscles on both sides predominantly evoked depolarizing potential in
      PBSt motoneurons and hyperpolarizing potential in GS motoneurons. The findings
      suggest that in general, tail muscle afferents facilitate flexor and inhibit
      extensor hindlimb motoneurons through polysynaptic pathways, so that the pelvic
      girdle is kept in a low position to maintain the stability of the body
      irrespective of different movements or posture of the tail.

PMID- 9555081
TI  - Cloning of a cyclic GMP phosphodiesterase gamma subunit from the ground squirrel
      retina.
AB  - Recent evidence suggests that the two main classes of cones are not only equipped
      with different photopigments, but also exhibit differences in their downstream
      phototransduction cascade. An antibody against the gamma subunit of retinal cGMP
      phosphodiesterase (PDE) had previously been found to label all photoreceptors in
      the ground squirrel (Spermophilus tridecemlineatus). This property was utilized
      for the cloning of a cDNA fragment encoding the corresponding polypeptide. A
      lambda gt11 cDNA library was constructed and screened with the antibody. Positive
      clones were isolated, subcloned, and sequenced. Clones were used as probes in RNA
      blot hybridization, and the obtained sequence information was compared to other
      available gamma-PDE sequences. Four virtually identical cDNA clones were
      isolated. Both nucleic acid and amino acid sequence alignment placed this gene in
      the same group as bovine and human cone gamma-phosphodiesterase subunits. The
      predicted length of the translated protein was 84 amino acids, and its molecular
      weight 11 kD. The cDNA hybridized with an 0.6-kb transcript in retinal RNA from
      ground squirrel, Syrian golden hamster, and mouse, and also with a 1.4-kb
      transcript in the ground squirrel. We conclude that the isolated cDNA fragment
      encodes a gamma subunit of cone cGMP-PDE. This subunit is expressed in middle
      wavelength sensitive cones (the predominant photoreceptor type in this species).
      It remains to be determined if this subunit is expressed in short-wavelength
      sensitive cones as well, or if these photoreceptors are equipped with another,
      unique gamma-PDE subunit.

PMID- 9555082
TI  - Cytotoxicity and DNA binding characteristics of dextran-conjugated doxorubicins.
AB  - The antitumor antibiotic doxorubicin was conjugated with polymeric dextrans of
      various molecular weights and the cytotoxicity of the conjugates against human
      carcinoma KB-3-1 cells and its multidrug-resistant subclone KB-V-1 cells was
      measured by tetrazolium salt MTT assay. The conjugates were much less toxic to
      the KB-3-1 cells than the free doxorubicin but exhibited similar toxicity to the
      KB-V-1 cells. The conjugate-DNA interactions were monitored in real-time using an
      optical biosensor based on evanescent wave detection to obtain the association
      (ka) and dissociation (kd) rate constants as well as the equilibrium binding
      constants (KA) of the bindings. Both ka and kd values for the conjugates are more
      than three magnitudes smaller than those for free doxorubicin, while the KA
      values of the conjugate-DNA complexes are only about 10 times smaller than that
      of the free doxorubicin-DNA complex. The results indicate that the cytotoxicity
      and the DNA-binding kinetics of doxorubicin may be modified with dextran
      conjugation. The KA values obtained from the biosensor measurements were in close
      agreement with those determined in solution by fluorescent titration method,
      verifying the utility of the label-free biosensing measurements as an efficient
      method for studying ligand-DNA interactions.

PMID- 9555083
TI  - Negative regulation of Apo A-I gene expression by retinoic acid in rat
      hepatocytes maintained in a coculture system.
AB  - Rat hepatocytes cocultured with rat liver epithelial cells (RLEC) were used to
      investigate the influence of all-trans retinoic acid (RA) on the regulation of
      apolipoproteins (Apo) A-I and A-II gene expression, the major protein constituent
      of high-density lipoproteins. In contrast to rat hepatocytes in conventional
      primary culture, Apo A-I and Apo A-II gene expression remained high and stable
      for several days in parenchymal cells in coculture. Treatment of cocultured rat
      hepatocytes with RA resulted in a specific decrease in Apo A-I mRNA levels
      whereas no marked difference in Apo A-II mRNA levels was observed. Such a
      negative effect of RA was already detected as early as 2 days of treatment and
      was effective for the entire experimental period (6 days). As controls, RARbeta
      mRNA levels increased whereas those of GAPDH mRNA were not affected by the RA
      treatment. The decrease in Apo A-I mRNA levels was associated with lower amounts
      of Apo A-I secreted in the culture medium within day 1 of treatment. This effect
      required active transcription and protein synthesis. These results show that,
      contrary to primary pure hepatocyte cultures and hepatoma cell lines, cocultures
      of rat hepatocytes reproduce the in vivo results suggesting that only well
      differentiated hepatocytes may correctly respond to RA. Furthermore, they
      demonstrate that RA can directly act on hepatocytes and differently affect Apo A
      I and Apo A-II gene expression.

PMID- 9555084
TI  - Post-lesion up-regulation of 5-HT1B binding sites in the suprachiasmatic nucleus
      may be reversed after spontaneous or graft-induced serotonin reinnervation.
AB  - We have previously reported that selective axotomy of serotoninergic neurons
      produced by an intraventricular injection of 5, 7-dihydroxytryptamine is followed
      by an increase in 5-HT1B binding sites in the suprachiasmatic nucleus of the
      hypothalamus. This post-lesion up-regulation is shown here to be spontaneously
      reversed after long-term survival in spite of an incomplete reinnervation of the
      nucleus. Recovery may be accelerated by fetal raphe transplants that produce more
      rapid reinnervation.

PMID- 9555085
TI  - Inhibition of cytochrome c oxidase activity by 4-hydroxynonenal (HNE). Role of
      HNE adduct formation with the enzyme subunits.
AB  - The role of 4-hydroxynonenal (HNE), a major lipid peroxidation product, in
      oxidative damage to mitochondrial cytochrome c oxidase (COX) was examined.
      Oxidative stress was induced in mitochondria isolated from livers of male Sprague
      Dawley rats by tert-butylhydroperoxide (t-BHP). COX activity was inhibited, with
      a concomitant increase in endogenous HNE level in mitochondria. COX activity was
      also inhibited following incubation of mitochondria with 50-450 microM HNE.
      Blocking HNE degradation intensified COX inhibition by HNE and by t-BHP-induced
      oxidative stress, the latter accompanied by a simultaneous increase in endogenous
      HNE production. On the other hand, COX inhibition by HNE was markedly reduced by
      potentiating HNE degradation via enhancing conjugation of HNE with reduced
      glutathione (GSH). Incubation of purified COX with 10-400 microM HNE resulted in
      HNE adduct formation with specific subunits of COX, correlated with inhibition of
      the enzyme activity. These data suggest that HNE may inhibit mitochondrial COX by
      forming adducts with the enzyme, and that this could be one mechanism underlying
      mitochondrial damage caused by oxidative stress. The findings also illustrate a
      role for GSH in protecting mitochondria from the deleterious effects of HNE.

PMID- 9555087
TI  - Noxious heat-evoked fos-like immunoreactivity in the rat lumbar dorsal horn is
      inhibited by glutamate microinjections in the upper cervical spinal cord.
AB  - Microinjections of glutamate into the upper cervical spinal cord significantly
      reduced (to 57% of control) the total number of neurons demonstrating noxious
      heat-evoked fos-like immunoreactivity in the lumbar spinal cord. Neurons in the
      upper cervical spinal cord, with descending propriospinal projections to the
      lumbar spinal cord, therefore, produce inhibitory effects on dorsal horn neurons
      in the lumbar spinal cord that receive nociceptive input from cutaneous thermal
      nociceptors.

PMID- 9555086
TI  - Neuromedin B activates phospholipase D through both PKC-dependent and PKC
      independent mechanisms.
AB  - The actions of neuromedin B (NMB), a recently discovered mammalian bombesin
      related peptide, are mediated by interacting with a distinct receptor; however,
      little is known about its cellular basis of action. Recent studies show
      activation of phospholipase D (PLD) is an important transduction cascade for a
      number of GI hormones, especially for stimulation of growth and protein sorting.
      The purpose of the present study was to determine whether activation of the NMB
      receptor causes activation of PLD and to explore whether this activation was
      coupled to PLC activation. Rat C6 glioblastoma cells (C6 cells), which contain a
      low density of native NMB receptors and BALB 3T3 cells stably transfected with
      rat NMB receptors, were used. NMB caused a 3-fold increase in C6 cells and an 11
      fold increase in rNMB-R transfected cells in PLD activity. Increases in PLD
      activity were rapid and NMB was 100-fold more potent than gastrin-releasing
      peptide (GRP). NMB caused a half-maximal increase in [Ca2+]i at 0.2 nM, in [3H]IP
      and PLD at 1 nM, and half-maximal receptor occupation at 1.2 nM. TPA increased
      PLD dose-dependently with a half-maximal effect at 60 nM. The calcium ionophore
      A23187 (1 microM) alone did not increase PLD activity but potentiated the effect
      of TPA. The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA
      stimulated PLD activities, although it blocked completely the NMB-induced
      increase in [Ca2+]i. The PKC inhibitor GF109203X completely abolished TPA-induced
      PLD activity, however, it only inhibited NMB-induced PLD activity by 20%. The
      combination of thapsigargin and GF109203X had the same effect as GF109203X alone.
      These data indicate that NMB receptor activation is coupled to both PLC and PLD.
      In contrast to a number of other phospholipase C-coupled receptors, NMB receptor
      stimulated changes in [Ca2+]i do not contribute to PLD activation. Both PKC
      dependent and PKC-independent mechanisms are involved in the NMB-stimulated PLD
      activation with the PKC-independent pathway predominating.

PMID- 9555088
TI  - Modification of dopamine release by nociceptin in conscious rat striatum.
AB  - Nociceptin (NOC), an endogenous ligand for the orphan receptor ORL1, has recently
      been recognized as a neuropeptide. We used brain microdialysis and on-line high
      performance liquid chromatography to examine the effect of NOC on the basal
      outflow of dopamine (DA) and its metabolite in the freely moving rat striatum in
      vivo. The percent change of DA release induced by NOC at concentrations of 10-6
      and 10-5 M were 383% and 398%, respectively. This effect of NOC was attenuated by
      naloxone, suggesting that NOC activates classic (micro, delta, kappa) receptors
      in a very little way. These data indicates that NOC may act as a neuropeptide
      which enhances DA release from the striatum of rat brain via an opioid receptor.

PMID- 9555089
TI  - Enhancement of intestinal UDP-glucuronosyltranferase activity in partially
      hepatectomized rats.
AB  - To evaluate whether a temporary hepatic insufficiency may affect intestinal
      glucuronidation, we determined UDP-glucuronosyltransferase activity towards
      bilirubin and p-nitrophenol in rat jejunum and liver after partial hepatectomy.
      Enzyme assays were performed in native, and in UDP-N-acetylglucosamine- or
      palmitoyl lysophosphatidylcholine-activated microsomes at different times post
      hepatectomy. Content of enzyme was analyzed by Western blot. Microsomal
      cholesterol/phospholipid ratio, phospholipid and total fatty acid classes were
      also determined to evaluate the possible influence on enzyme activity. The
      results show that while hepatic microsomes exhibited no change in UDP
      glucuronosyltransferase activity (for both substrates) with respect to shams at
      any time of study, intestinal activities increased significantly 48 h after
      surgery, returning to sham values 96-h post-hepatectomy. Western blotting
      confirmed the increase (about 50% for both substrates 48-h post-hepatectomy) in
      intestinal UDP-glucuronosyltransferase activity. No variations were observed in
      hepatic and intestinal microsomal lipid composition in agreement with the absence
      of modification in the percent of activation by palmitoyl
      lysophosphatidylcholine. In conclusion, jejunum but not liver, was able to
      produce a compensatory increase in conjugation capacity during a transitory loss
      of hepatic mass. The phenomenon is associated to a modification in the amount of
      UDP-glucuronosyltransferase, rather than to changes in the characteristics of the
      enzyme environment.

PMID- 9555090
TI  - Anxiolytic-like effect of neuropeptide Y (NPY) and NPY13-36 microinjected into
      vicinity of locus coeruleus in rats.
AB  - Neuropeptide Y (NPY, 1 and 10 pmol), NPY Y1 receptor agonist [Leu31, Pro34]NPY
      (10 pmol) and Y2 agonist NPY13-36 (100 pmol) were administered unilaterally into
      the region of the nucleus locus coeruleus (LC) in rats. NPY (10 pmol) and NPY13
      36 increased the percentage of open arm entries, the percentage of time spent on
      open part, number of both open and closed arm entries and line crossings in the
      open part while [Leu31,Pro34]NPY failed to modify elevated plus-maze behavior.
      These data suggest that NPY applied close to LC has anxiolytic-like effects by
      acting on NPY Y2, not on Y1 receptors. Thus, NPY Y2 receptors in the vicinity of
      LC may be involved in the regulation of anxiety in rats.

PMID- 9555091
TI  - Organization of quinto-frontal structures in hatchling ring doves (Streptopelia
      risoria).
AB  - Transganglionic and retrograde tracing procedures were applied to peripheral and
      central trigeminal structures in hatchling ring doves. The organization of the
      trigeminal ganglion, its somatotopic projections upon the principal sensory
      nucleus (PrV), and the projections of PrV upon the telencephalon are similar in
      adult and hatchling Columbiformes. The results suggest that development of
      feeding patterns in these species involves experiential differentiation of
      trigeminal sensorimotor circuits present at hatching.

PMID- 9555092
TI  - Pristanic acid beta-oxidation in peroxisomal disorders: studies in cultured human
      fibroblasts.
AB  - To investigate the individual steps of peroxisomal beta-oxidation, human
      fibroblasts from controls and patients affected by different peroxisomal
      disorders were incubated for 96 h with pristanic acid. Hereafter, 2,3-pristenic
      acid and 3-hydroxypristanic acid in the incubation medium were quantified by
      stable isotope dilution gas chromatography mass spectrometry (GC-MS). In control
      fibroblasts, both intermediates were formed and excreted into the medium in
      significant amounts. In cells from patients affected with different types of
      generalized peroxisomal disorders, the formation of both intermediates was absent
      or low, depending on the clinical severity of the disorder. In fibroblasts from
      patients affected with bifunctional protein deficiency, the concentrations of 2,3
      pristenic acid and 3-hydroxypristanic acid in the medium were higher than in
      control cell lines.

PMID- 9555093
TI  - 7-Nitro indazole enhances methohexital anesthesia.
AB  - 7-nitro indazole, a selective inhibitor of the neuronal nitric oxide (NO)
      synthase dose-dependently prolongs the duration of methohexital narcosis in the
      rat. This effect can be antagonized stereoselectively by the NO-synthase
      substrate l-arginine (l-Arg). The results support the assumption that the
      potentiation of the anesthetic state by NO-synthase inhibitors is due to a
      specific effect on brain NO-synthase and a disruption of synaptic NO signalling
      pathways. These results are also in accordance with predictions that follow from
      recent hypotheses proposing that a modification of the NMDA receptor function is
      the final common pathway of anesthetic action.

PMID- 9555094
TI  - Novel vectors for gene delivery formed by self-assembly of DNA with poly(L
      lysine) grafted with hydrophilic polymers.
AB  - Complexes formed between DNA and cationic polymers are attracting increasing
      attention as novel synthetic vectors for delivery of genes. We are trying to
      improve biological properties of such complexes by oriented self-assembly of DNA
      with cationic-hydrophilic block copolymers, designed to enshroud the complex
      within a protective hydrophilic polymer corona. Poly(L-lysine) (pLL) grafted with
      range of hydrophilic polymer blocks, including poly(ethylene glycol) (pEG),
      dextran and poly[N-(2-hydroxypropyl)methacrylamide] (pHPMA), shows efficient
      binding to DNA and mediates particle self-assembly and inhibition of ethidium
      bromide/DNA fluorescence. The complexes formed are discrete and typically about
      100 nm diameter, viewed by atomic force microscopy. Surface charges are slightly
      shielded by the presence of the hydrophilic polymer, and complexes generally show
      decreased cytotoxicity compared with simple pLL/DNA complexes. pEG-containing
      complexes show increased transfection activity against cells in vitro. Complexes
      formed with all polymer conjugates showed greater aqueous solubility than simple
      pLL/DNA complexes, particularly at charge neutrality. These materials appear to
      have the ability to regulate the physicochemical and biological properties of
      polycation/DNA complexes, and should find important applications in packaging of
      nucleic acids for specific biological applications.

PMID- 9555095
TI  - Arginyl residues are involved in acyl-CoA binding to the elongase from etiolated
      leek seedlings.
AB  - The C18:0-CoA elongase from etiolated leek seedling microsomes was inactivated by
      treatment with phenylglyoxal, a reagent which specifically modifies arginyl
      residues. In the presence of 20 mM phenylglyoxal, 95% of the C18:0-CoA elongation
      was inhibited. The condensation and dehydration reactions of the overall
      elongation were totally inhibited, whereas enoyl-CoA reductase activity was
      diminished by 75%, but the nature of the final elongation product was unchanged.
      Phenylglyoxal did not modify the C18:0-CoA partition between membrane and aqueous
      compartments; moreover, [1-14C]phenylglyoxal labeling experiments showed a
      covalent binding of the inhibitor to membrane proteins. The ability of several
      substrates to prevent the inactivation by phenylglyoxal was investigated. NADH
      and NADPH had no effect. CoA led to a 75% protection, and the incorporation of
      [14C]phenylglyoxal was strongly affected by 10 mM CoA. The acyl chain length of
      the acyl-CoAs played also a crucial role in preventing the binding of
      phenylglyoxal. The maximal prevention of phenylglyoxal inhibition was obtained
      with C18:0-CoA. This suggests that arginyl residues could be present in the
      vicinity of the acyl-CoA binding site of the subunits of C18:0-CoA elongase.

PMID- 9555096
TI  - Inhibition of secreted phospholipases A2 by annexin V. Competition for anionic
      phospholipid interfaces allows an assessment of the relative interfacial
      affinities of secreted phospholipases A2.
AB  - The ability of annexins, particularly annexin 1 (lipocortin 1), to inhibit
      phospholipase A2 (PLA2) is well known and a substrate depletion mechanism is now
      widely accepted as the explanation for most inhibitory studies. In this
      investigation we have examined the substrate depletion mechanism of annexin V
      using a variety of phospholipid substrates and secreted PLA2's (sPLA2). The
      results suggest that the term interfacial competition best describes the
      inhibitory effect of annexin V although the overall inhibitory process remains
      one of substrate sequestration by the annexin. We have utilised the competitive
      nature of the interaction of enzyme and annexin V for a phospholipid interface as
      a means of quantifying the relative affinity of sPLA2's for anionic phospholipid
      vesicles. The results highlight the very high affinity of the human non
      pancreatic sPLA2 for such vesicles (Kd<<10-(10) M) while the Naja naja venom PLA2
      and porcine pancreatic sPLA2 showed lower affinities. Hydrolysis of mixed
      vesicles containing phosphatidylserine and phosphatidylcholine by the venom and
      pancreatic enzymes were differentially inhibited by annexin V. This difference
      must reflect the preference of both annexin V and the pancreatic enzyme for an
      anionic phospholipid interface. In contrast, the venom enzyme is able to readily
      hydrolyse phosphatidylcholine domains that would be minimally affected by annexin
      V. Annexin V was an effective inhibitor of cardiolipin hydrolysis by the
      pancreatic PLA2, however the inhibition was of a more complex nature than seen
      with other phospholipids tested. Overall the results highlight the ability of
      annexin V to inhibit phospholipid hydrolysis by sPLA2's by an interfacial
      competition (substrate depletion) mechanism. The effectiveness of annexin V as an
      apparent inhibitor depends on the nature of the enzyme and the phospholipid
      substrate.

PMID- 9555097
TI  - Serum DNA polymerase beta as an indicator for fatal liver injury of rat induced
      by D-galactosamine hydrochloride and lipopolysaccharide.
AB  - DNA polymerase beta (pol beta) is a nuclear enzyme that is tightly bound to
      chromatin. Release of the pol beta activity into serum, therefore, may indicate
      the occurrence of massive destruction of cell nuclei in organs or tissues. In the
      present study, we made a liver injury model rat by the intraperitoneal injection
      of D-galactosamine hydrochloride (GalN, 500 mg/kg) and lipopolysaccharide (LPS,
      100 microg/kg). Serum from the GalN/LPS-treated rats showed a high level of pol
      beta activity up to 118 pmol/0.5 microl serum (4700 cpm) at 12 h after the
      treatment, while the control rat serum showed the back ground level (3.8 pmol/0.
      5 microl, 150+/-70 cpm). The serum pol beta activity was sensitive to inhibition
      by 2',3'-dideoxyTTP and by an anti-rat pol beta antibody. Among 30 rats treated
      with GalN/LPS, 10 rats died within 120 h (dead group). Serum pol beta activity in
      the dead group was as high as 23.0+/-19.5 pmol/0.5 microl (925+/-778 cpm) at 10 h
      after the treatment, while in alive group (n=20), it was 3.7+/-3.2 pmol. Levels
      of the serum pol beta activity correlated well with the prognosis of GalN/LPS
      treated rats based on an analysis of the receiver-operator characteristic curves.

PMID- 9555098
TI  - Characterization of hyaluronan synthase from a human glioma cell line.
AB  - In the present study we describe a method to prepare membranes with high
      hyaluronan synthase activity from human glioma cells by pretreatment of the cells
      with both testicular hyaluronidase and 4-phorbol 12-myristate 13-acetate (PMA). A
      23-fold increase in hyaluronan synthase activity was detected in comparison to
      untreated cells. Using isolated membranes as a source of hyaluronan synthase
      activity we demonstrate that chain elongation occurs at the reducing end of the
      hyaluronan molecule. We also present a method to solubilize hyaluronan synthase
      in active form with 1% digitonin. The solubilized synthase synthesized shorter
      hyaluronan chains than the membrane bound enzyme. Partial purification of the
      solubilized enzyme on a Superdex-200 column revealed a 12-fold increase in
      specific activity. Affinity purified polyclonal antibodies, raised against a
      synthetic peptide corresponding to the carboxy-terminus of the deduced protein
      sequence of human hyaluronan synthase recognized a 66 kDa component in the
      purified preparations. The elution position of the solubilized hyaluronan
      synthesizing activity immediately after V0 corresponding to a molecular mass of
      about 600 kDa, suggested that the 66 kDa enzyme forms a complex with other
      components which may have accessory or regulatory roles during hyaluronan
      synthesis.

PMID- 9555099
TI  - Interaction of mercaptoundecahydrododecaborate (BSH) with phosphatidylcholine:
      relevance to boron neutron capture therapy.
AB  - The interaction of mercaptoundecahydrododecaborate (B12H11SH2-, BSH) with
      phosphatidylcholine was investigated in this study in order to illuminate
      possible uptake mechanisms of BSH in tumor cells. BSH has been used clinically in
      Japan as a boron containing agent in patients with malignant brain tumors for
      boron neutron capture therapy (BNCT). After infusion, BSH accumulates selectively
      in tumor tissue. Little is known for the mechanism of boron uptake to tumor
      cells. Fourier transform infrared (FTIR) spectrometry was used to quantify BSH
      (at wavenumber 2490 cm-1) and phosphatidylcholine (at wavenumber 2850-2970 cm-1).
      After extraction into carbon tetrachloride (CCl4), we could find an absorbance
      maximum at 2490 cm-1 as a B-H band in the mixture of BSH with
      phosphatidylcholine, which is attributed to a BSH-phosphatidylcholine complex,
      which could dissolve well in CCl4. The molar ratio of BSH to phosphatidylcholine
      in the CCl4 solution was at most one mole of BSH to two moles of
      phosphatidylcholine independent of the excess BSH. The doubly negatively charged
      BSH can interact with two phosphatidylcholine molecules through their singly
      positively charged choline residues. These ion pairs could be responsible for
      membrane binding and penetration, and for cell internalization.

PMID- 9555100
TI  - Cloning and expression of a group IV cytosolic Ca2+-dependent phospholipase A2
      from rat pancreatic islets. Comparison of the expressed activity with that of an
      islet group VI cytosolic Ca2+-independent phospholipase A2.
AB  - Stimulation of pancreatic islets with glucose induces phospholipid hydrolysis and
      accumulation of nonesterified arachidonic acid, which may play signaling or
      effector roles in insulin secretion. Of enzymes that catalyze phospholipid
      hydrolysis, islet beta-cells express low molecular weight secretory
      phospholipases A2 (PLA2) and a Group VI, Ca2+-independent PLA2 (iPLA2). Previous
      studies indicate that islets also express a protein recognized by antibodies
      against a Group IV, cytosolic, Ca2+-dependent PLA2 (cPLA2). To further examine
      the possible expression of cPLA2 by islets, we screened a rat islet cDNA library
      with a probe that recognizes cPLA2 sequence, and isolated a full-length cPLA2
      cDNA. The rat islet cPLA2-deduced amino acid sequence is 96% identical to those
      of human and mouse cPLA2. Transfection of COS-7 cells with cPLA2 cDNA in an
      expression vector induced expression of Ca2+-dependent PLA2 activity and of a
      protein recognized by anti-cPLA2 antibody. Comparison of recombinant islet cPLA2
      and iPLA2 activities expressed in transfected COS-7 cells indicated that iPLA2
      but not cPLA2 is stimulated by ATP. Both activities are similarly sensitive to
      inhibition by arachidonyltrifluoromethyl ketone, but iPLA2 is more effectively
      inhibited by a haloenol lactone suicide substrate than cPLA2. RT-PCR experiments
      with RNA from purified islet beta-cells and from an alpha-cell-enriched
      population prepared by fluorescence-activated cell-sorting indicated that cPLA2
      mRNA is more abundant in the beta-cell population. Immunoblotting analyses
      indicate that islets express cPLA2-immunoreactive protein, and that interleukin-1
      does not affect its expression. The cPLA2 is thus one of at least three classes
      of PLA2 enzymes with distinct properties expressed in beta-cells.

PMID- 9555101
TI  - Erythrocyte defenses against hydrogen peroxide: the role of ascorbic acid.
AB  - Ascorbate has been reported to increase intracellular hydrogen peroxide (H2O2)
      generation in human erythrocytes. In the present work, the basis for this
      prooxidant effect of the vitamin was investigated in the context of erythrocyte
      defenses against H2O2. Ascorbate added to erythrocytes caused a dose-dependent
      increase in intracellular H2O2, which was measured as inactivation of endogenous
      catalase in the presence of 3-amino-1,2,4-triazole (aminotriazole). Ascorbate
      induced catalase inactivation was not observed when only the intracellular
      ascorbate concentration was increased, when cells were incubated with ascorbate
      in plasma, or when extracellular Fe3+ was chelated. Together, these results
      suggest that the observed ascorbate-induced H2O2 generation is due to Fe3+
      catalyzed oxidation of extracellular, as opposed to intracellular, ascorbate by
      molecular oxygen. Rather than generate an oxidant stress in erythrocytes,
      ascorbate was one of the most sensitive intracellular antioxidants to H2O2 coming
      from outside the cells. On the other hand, intracellular ascorbate contributed
      little to the detoxification of H2O2, which was found to be mediated by both
      catalase and by the GSH system.

PMID- 9555102
TI  - Hypoxia and contractions do not utilize the same signaling mechanism in
      stimulating skeletal muscle glucose transport.
AB  - We have investigated whether hypoxia and muscle contractions stimulate glucose
      transport in perfused rat muscle to the same extent, additively and with the same
      sensitivity to the microbial products calphostin C and wortmannin. Hindlimb
      glucose uptake increased gradually from 3.4+/-0.5 to a maximal level of 12.7+/
      0.6 micromol g-1 h-1 (n=11) after 50 min of hypoxia. Compared with hypoxia, the
      effect of maximal electrical stimulation of the sciatic nerve on muscle glucose
      uptake was more than two-fold higher (27+/-2 micromol g-1 h-1 (n=14)). This was
      due to a higher contraction- vs. hypoxia-induced glucose transport rate in
      oxidative fibers. The stimulatory effect of hypoxia and electrical stimulation
      was not additive. Contraction-induced muscle glucose transport was inhibitable by
      both calphostin C and wortmannin in the micromolar range, whereas the effect of
      hypoxia was totally insensitive to these drugs. Our data suggest that
      diacylglycerol/phorbol ester-sensitive protein kinase C is involved in
      stimulation of muscle glucose transport by contractions and that in contrast to
      the prevailing concept, hypoxia and contractions do not stimulate muscle glucose
      transport by the same signaling mechanism.

PMID- 9555103
TI  - Distinctive inhibitory activity of docosahexaenoic acid against sphingosine
      induced apoptosis.
AB  - The effect of supplementation of docosahexaenoic acid (DHA) on the apoptosis of
      HL60 cells was examined using N-acetyl sphingosine (C2-ceramide) and sphingosine
      as apoptosis-inducing agents. Although C2-ceramide-induced apoptosis was not
      affected by DHA supplementation, sphingosine-induced apoptosis was reduced almost
      to the background level by preincubation with 10 microM DHA for 24 h. Among the
      fatty acids, only DHA appeared to be endowed with the ability to reduce
      sphingosine-induced apoptosis, whereas, other unsaturated fatty acids, such as
      arachidonic acid (AA) and eicosapentaenoic acid (EPA), did not show this
      activity. Incubation of HL60 with DHA within 6 h did not affect the apoptosis,
      suggesting that DHA probably expressed the inhibitory activity after modulation
      of the membrane fatty acid composition. DHA also attenuated the apoptosis induced
      by dimethylsphingosine and H-7, but not by calphostin C, indicating that
      enrichment of DHA in membranous phospholipid does not necessarily prevent all of
      the apoptosis associated with the inhibition of protein kinase C. The mechanism
      of the inhibition against sphingosine-induced apoptosis by DHA remains to be
      further explored. However, the inhibition of cytosolic phospholipase A2 (cPLA2)
      may be involved in the mechanism, because distinctive inhibitory activity of DHA
      against cPLA2 has been demonstrated [M. Shikano, Y. Masuzawa, K. Yazawa, K.
      Takayama, I. Kudo, K. Inoue, Biochim. Biophys. Acta, 1212, 1994, 211-216], and
      arachidonyl trifluoromethylketone, a specific inhibitor of cPLA2, attenuated the
      apoptosis induced by sphingosine.

PMID- 9555104
TI  - Modular subdivisions of dolphin insular cortex: does evolutionary history repeat
      itself?
AB  - The structural organization of the insular cortex in the bottlenose dolphin was
      investigated by examining Nissl- and myelin-stained tissue that was sectioned
      coronally and tangentially. An uneven distribution of cell clusters that
      coincided with myelin-light zones was observed in layer II. When the present
      observations were compared to descriptions of modules in other animals, we found
      that the range of module size is restricted, while the size of the brain,
      particularly the neocortex, varies dramatically. Indeed, despite the tremendous
      expansion of the cetacean neocortex, the size of the modules in the insular
      cortex is similar to that described for small-brained mammals like the mouse,
      suggesting that module size is evolutionarily stable across species. Selection
      for optimal-size processing units, in terms of the lengths of connections within
      and between them, is a likely source of this stability.

PMID- 9555105
TI  - Contribution of human prefrontal cortex to delay performance.
AB  - Neurological patients with focal lesions in the dorsolateral prefrontal cortex
      and age-matched control subjects were tested on an auditory version of the
      delayed-match-to-sample task employing environmental sounds. Subjects had to
      indicate whether a cue (s/S1) and a subsequent target sound (S2) were identical.
      On some trials, S1 and S2 were separated by a silent period of 5 sec. On other
      trials, the 5-sec delay between S1 and S2 was filled with irrelevant tone pips
      that served as distractors. Behaviorally, frontal patients were impaired by the
      presence of distractors. Electrophysiologically, patients generated enhanced
      primary auditory cortex-evoked responses to the tone pips, supporting a failure
      in inhibitory control of sensory processing after prefrontal damage.
      Intrahemispheric reductions of neural activity generated in the auditory
      association cortex and additional intrahemispheric reductions of attention
      related frontal activity were also observed in the prefrontal patients. Together,
      these findings suggest that the dorsolateral prefrontal cortex is crucial for
      gating distracting information as well as maintaining distributed
      intrahemispheric neural activity during auditory working memory.

PMID- 9555106
TI  - Toward a functional analysis of the basal ganglia.
AB  - Parkinson patients were tested in two paradigms to test the hypothesis that the
      basal ganglia are involved in the shifting of attentional set. Set shifting means
      a respecification of the conditions that regulate responding, a process sometimes
      referred to as an executive process. In one paradigm, upon the appearance of each
      stimulus, subjects were instructed to respond either to its color or to its
      shape. In a second paradigm, subjects learned to produce short sequences of three
      keypresses in response to two arbitrary stimuli. Reaction times were compared for
      the cases where set either remained the same or changed for two successive
      stimuli. Parkinson patients were slow to change set compared to controls.
      Parkinson patients were also less able to filter the competing but irrelevant set
      than were control subjects. The switching deficit appears to be dopamine based;
      the magnitude of the shifting deficit was related to the degree to which 1-dopa
      based medication ameliorated patients' motor symptoms. Moreover, temporary
      withholding of medication, a so-called off manipulation, increased the time to
      switch. Using the framework of equilibrium point theory of movement, we discuss
      how a set switching deficit may also underlie clinical motor disturbances seen in
      Parkinson's disease.

PMID- 9555107
TI  - Self-organization of binocular disparity tuning by reciprocal corticogeniculate
      interactions.
AB  - This article develops a neural model of how sharp disparity tuning can arise
      through experience-dependent development of cortical complex cells. This learning
      process clarifies how complex cells can binocularly match left and right eye
      image features with the same contrast polarity, yet also pool signals with
      opposite contrast polarities. Antagonistic rebounds between LGN ON and OFF cells
      and cortical simple cells sensitive to opposite contrast polarities enable
      anticorrelated simple cells to learn to activate a shared set of complex cells.
      Feedback from binocularly tuned cortical cells to monocular LGN cells is proposed
      to carry out a matching process that dynamically stabilizes the learning process.
      This feedback represents a type of matching process that is elaborated at higher
      visual processing areas into a volitionally controllable type of attention. We
      show stable learning when both of these properties hold. Learning adjusts the
      initially coarsely tuned disparity preference to match the disparities present in
      the environment, and the tuning width decreases to yield high disparity
      selectivity, which enables the model to quickly detect image disparities.
      Learning is impaired in the absence of either antagonistic rebounds or
      corticogeniculate feedback. The model also helps to explain psychophysical and
      neurobiological data about adult 3-D vision.

PMID- 9555108
TI  - Neural site of the redundant target effect electrophysiological evidence.
AB  - The present study represents an attempt to find an electrophysiological correlate
      of the redundant targets effect, or RTE (i.e., the speeding up of reaction time,
      or RT, for redundant vs. single targets). Subjects made a speeded response either
      to one small checkerboard presented to the left or right of fixation or to a pair
      of identical checkerboards presented simultaneously to both hemifields. Both
      single and double targets could appear either in the upper or lower visual
      hemifield. The task required detection but not discrimination of the stimuli.
      During task performance, we recorded the event-related potentials (ERPs) elicited
      by the checkerboard targets. As in previous studies, we found that manual RTs to
      bilateral stimuli were faster than those to unilateral stimuli. This effect was
      more marked for lower- than for upper-field stimuli and could not be ascribed to
      probability summation. In addition, we found that the P1 and N1 components of the
      visual ERP had a shorter latency for bilateral than for summed unilateral stimuli
      presented to the two hemifields. In parallel with the behavioral findings, the
      latency values for the above components showed a larger RTE for lower-field
      stimuli. These findings indicate that the RTE occurs at the level of early visual
      processing, probably in the extrastriate visual cortex, rather than at late
      decisional or pre-motor stages.

PMID- 9555109
TI  - Cortical-hippocampal auditory processing identified by magnetoencephalography.
AB  - We recorded magnetic and electrical responses simultaneously in an auditory
      detection task to elucidate the brain areas involved in auditory processing.
      Target stimuli evoked magnetic fields peaking at approximately the same latency
      of around about 400 msec (M400) over the anterior temporal, superior temporal,
      and parietal regions on each hemisphere. Equivalent current dipoles (ECDs) were
      analyzed with a time-varying multidipole model and superimposed on each subject's
      magnetic resonance image (MRI). Multiple independent dipoles located in the
      superior temporal plane, inferior parietal lobe, and mesial temporal region best
      accounted for the recorded M400 fields. These findings suggest that distributed
      activity in multiple structures including the mesial temporal, superior temporal,
      and inferior parietal regions on both hemispheres is engaged during auditory
      attention and memory updating.

PMID- 9555110
TI  - Encapsulation of implicit and explicit memory in sequence learning.
AB  - Contrasts between implicit and explicit knowledge in the serial reaction time
      (SJRT) paradigm have been challenged because they have depended on a single
      dissociation; intact implicit knowledge in the absence of corresponding explicit
      knowledge. In the SRT task, subjects respond with a corresponding keypress to a
      cue that appears in one of four locations. The cue follows a repeating sequence
      of locations, and subjects can exhibit knowledge of the repeating sequence
      through increasingly rapid performance (an implicit test) or by being able to
      recognize the sequence (an explicit test). In our study, amnesic patients were
      given extensive SRT training. Their implicit and explicit test performance was
      compared to the performance of control subjects who memorized the training
      sequence. Compared with control subjects, amnesic patients exhibited superior
      performance on the implicit task and impaired performance on the explicit task.
      This crossover interaction suggests that implicit and explicit knowledge of the
      embedded sequence are separate and encapsulated and that they presumably depend
      on different brain systems.

PMID- 9555111
TI  - Event-related brain potentials and case information in syntactic ambiguities.
AB  - In an ERP study, German sentences were investigated that contain a case-ambiguous
      NP that may be assigned accusative or dative case. Sentences were disambiguated
      by the verb in final position of the sentence. As our data show, sentences ending
      in a verb that assigns dative case to the ambiguous NP elicit a clear garden-path
      effect. The garden-path effect was indicated by a broad centro-posterior negative
      shift that occurred between 300 and 900 msec after the dative-assigning verb was
      presented. No enhanced P600 following the misanalysis was observed. Noun phrases
      whose case ambiguity was resolved in favor of accusative case and unambiguously
      dative-marked NPs did not trigger significant ERP differences. We will discuss
      the implications of our results for parsing and its neuropsychological
      correlates. The results of this study support a parser design according to which
      the so-called structural case (nominative or accusative) is assigned without any
      delay in the absence of morpho-lexical counterevidence. It is argued that the
      enhancement of a negative ERP component with a "classical" N400 topography
      reflects the difficulty of reanalysis due to reaccessing morpho-lexical
      information that lies outside the domain of the parsing module. Consequently, ERP
      responses to garden-path effects are not confined to a late positivity but vary
      depending on the level of processing involved in reanalysis. The fact that garden
      path effects may also elicit an N400 can be linked to the nonhomogeneous
      linguistic properties of the constructions from which they arise.

PMID- 9555112
TI  - The neurology of empty categories aphasics' failure to detect ungrammaticality.
AB  - A direct investigation into the grammatical abilities of Broca's and Wernicke's
      aphasics sought to obtain critical evidence for a revised model of the functional
      neuroanatomy of language. We examined aphasics' ability to make grammaticality
      judgments on a set of theoretically selected, highly complex syntactic structures
      that involve, most prominently, fine violations of constraints on syntactic
      movement. Although both groups have been thought to possess intact abilities in
      this domain, we discovered severe deficits; Broca's and Wernicke's aphasics
      (whose performances differed) exhibited clear, delineated, and grammatically
      characterizable deficits - they follow from the Trace-Deletion Hypothesis, which
      is motivated by independent comprehension results. These conclusions have both
      linguistic and neurological implications; Linguistically, they show that the
      aphasic deficit interacts with more than one module of the grammar. Namely, it
      manifests not only when the thematic module is called for in interpretive tasks
      but also when constraints on syntactic movement are tapped in a study of
      judgment. Neurologically, the results support a view of receptive grammatical
      mechanisms in the left cortex, which is functionally more restrictive than
      currently assumed; neuroanatomically, however, it is more distributed.

PMID- 9555113
TI  - The complexity of the Epstein-Barr virus infection in humans.
AB  - The Epstein-Barr virus (EBV) was isolated 40 years ago from cultures of Burkitt
      lymphoma cells (BL). The tumor was encountered in Africa and exhibited
      characteristical geographical, clinical and pathological features. Serological
      studies revealed that the virus is ubiquitous in humans. The primary infection is
      often accompanied by the syndrome of acute infectious mononucleosis (IM). It can
      induce malignant proliferation of B lymphocytes in conditions of
      immunodeficiency. EBV can immortalize B lymphocytes in culture. These cells carry
      the virus as episomes and express 9 virally encoded proteins. Their immunological
      recognition constitutes the surveillance which is responsible for the healthy
      virus carrier state. The main virus reservoir is represented by a low number of
      resting B lymphocyte which contain the viral genome but do not express its
      transformation proteins. The viral genome is detectable in all African BLs, in
      variable proportions of nasopharyngeal carcinoma, Hodgkin's disease, T cell
      lymphoma, lymphoepithelial like carcinoma, gastric carcinoma and leiomyosarcoma
      cases. The role of EBV in the genesis of these tumors is unknown.

PMID- 9555114
TI  - P53 expression in stage I squamous cell lung cancer.
AB  - P53 expression was studied using immunohistochemistry in patients (n=94) with
      pathologic stage I squamous cell lung cancer treated surgically between 1991
      1992. The overall p53 positivity ratio was 48/94. 83 of the cases proved to be
      suitable for follow-up analysis carried out in November, 1995. 46/83 were p53
      positive, and 25/46 patients were alive at the time of analysis. The patients who
      died (21/46) had a mean survival time of 17.5 months. In p53 negative cases
      (37/83), however, 29/37 patients were still alive at the time of follow-up, and
      8/37 had died with a mean survival time of 23.1 months. A significant correlation
      could be found between p53 immunopositivity and reduced survival time (p=0.0125).
      Interestingly, out of 83 cases analyzed histologic evidence of tuberculous scar
      tissue was present in 9 tumors with a p53 positivity ratio of only 1/9. When flow
      cytometry was used to examine tumor samples from all subgroups mentioned above
      (n=32), no correlation was found between the p53 immunopositivity or the
      prognosis and the DNA content of tumor tissues. Our results suggest that in the
      early stage of squamous cell lung cancer the p53 positivity may be an indicator
      of a more aggressive tumor behavior and a shortened survival time.

PMID- 9555115
TI  - Expression of invasion markers CD44v6/v3, NM23 and MMP2 in laryngeal and
      hypopharyngeal carcinoma.
AB  - Twelve laryngeal squamous cell carcinoma cases (7 laryngeal and 5 hypopharyngeal
      cancer; 15 samples) were analysed by immunohistochemistry for the expression of
      invasion markers CD44v6/v3, NM23 and matrix metalloproteinase, MMP2. The
      laryngeal epithelium showed CD44v6+/v3+/NM23-/MMP2- phenotype. When tumors were
      grouped into TNM categories the phenotype of the T2 and T3 tumors was similar,
      characterised by decreased CD44v3+ and lack of MMP2 expressions. Meanwhile the
      NM23 expression was more frequent in T3 tumors. In T4 stage the frequency of NM23
      and MMP2 positive cases increased (5/6 and 4/6, respectively) but there was no
      correlation with the appearence of lymph node metastasis. Comparison of the
      phenotype of laryngeal and hypopharyngeal tumors, irrespective of the TNM stages,
      revealed characteristic differences: T2 stage laryngeal tumors showed decreased
      CD44v3 and occasional NM23 and MMP2 positivity, while in T3 stage these tumors
      were characterised by increased frequency of NM23 positivity. The phenotype of
      the hypopharyngeal tumors was significantly different with a high frequency of
      MMP2 positive cases (5/6) and NM23+/low CD44v3+ phenotype. The sharp differences
      in the phenotypes of laryngeal and hypopharyngeal carcinomas were connected to
      the differences in their invasive capacity unlike to the size of the tumors,
      since the T4 stage hypopharyngeal tumors had a significantly smaller size than
      laryngeal ones, even at lower stages.

PMID- 9555116
TI  - Cellular alterations upon IR-laser (890 nm) exposures, in vivo.
AB  - Exposure of cultured cells and small animals to ionizing radiation as well as
      irradiation of cultured cells with He-Ne laser can cause changes in the
      functional condition of plasma membranes. The ionizing radiation-induced cell
      membrane alterations have been determined after either partial or local
      exposures. The aim of the present study was to reveal whether the local laser
      treatments cause a general, distant, so called abscopal" effect measured at
      cellular level, when the laser treatment is intended as a stimulatory procedure.
      The biological effect of infrared laser (mean power of 5 Watts, 150 Hz frequency,
      890 nm wavelength) was demonstrated through 3H-concanavalin A binding by blood
      cells of daily irradiated (altogether 10 exposures) oncological and non
      oncological patients as well as by changes in the proliferation of bone marrow
      cells of whole body gamma-irradiated (4 Gy) rats, partially laser-treated. The
      lectin binding of lymphocytes of oncological, as well as ischaemic heart disease
      patients was increased immediately after the first laser treatment. However, it
      was decreased after completion of the full course. In cases of inflammatory
      diseases the test parameters were either unchanged or decreased as compared to
      their self-control values. The platelets and erythrocytes did not react in any
      group. Gamma irradiation caused a deep inhibition of proliferation of rat bone
      marrow cells. The number of fibroblast colony-forming units (CFU-F) could be
      increased again if the animals were partially exposed to laser. Laser irradiation
      of one of the femurs led to some recovery of CFU-F values in the exposed as well
      as unexposed femur. Thus, local infrared laser treatment induces abscopal effects
      on the cell membrane and cell proliferation characteristics.

PMID- 9555117
TI  - Embryotoxicity and teratogenicity of some derivatives of
      chloroethylaminophenylacetic acid.
AB  - Embryotoxic and teratogenic properties of Lophenal, Phenalon, Pharanox and
      Pharanoxi selenate were investigated experimentally. All examined antitumour
      agents showed embryotoxic effects. Lophenal, Phenalon and Pharanox had
      teratogenic effects. By modifying the structure of Pharanox with selenium a
      reduction in teratogenic effect was achieved.

PMID- 9555118
TI  - Comparison of the effects of the antimetastatic compound ImH[trans-RuCl4(DMSO)Im]
      (NAMI-A) on the arthritic rat and on MCa mammary carcinoma in mice.
AB  - The effects of the new molecule ImH[trans-RuCl4(DMSO)Im] (NAMI-A), administered
      orally or intraperitoneally to adjuvant-arthritic rats or orally to mice bearing
      s.c. or i.m. implants of MCa mammary carcinoma, were studied. NAMI-A was not able
      to modify the progression of chronic inflammation in the complete Freund-adjuvant
      injected animals. Histology indicated a significant worsening of the inflammatory
      process, characterised by an increased infiltration of inflammatory cells, as
      well as by a remarkable deposition of connective tissue fibres around the blood
      vessels and alveolar walls. NAMI-A had no effect on primary i.m. implanted MCa
      mammary carcinoma growth and its lung metastasis formation, but significantly
      interfered with the cell cycle of primary tumor cells following bolus oral
      administration. On the contrary, NAMI-A caused a significant inhibition of lung
      metastasis accompanied by a dramatic deposition of connective tissue fibres
      around the primary tumor mass, when given as medicated food to mice implanted
      s.c. with MCa tumor. These data indicated that NAMI-A is well absorbed after oral
      administration although there is no connection between lung concentration and the
      antimetastatic activity. Conversely, the marked deposition of connective tissues
      in NAMI-A treated animals is in agreement with the reported effects of the
      compound on extracellular matrix and tumor blood vessels.

PMID- 9555119
TI  - Coronary vasculopathy in polycythemia vera.
AB  - Thrombosis is a common complication in polycythemia often causing death. In
      coronary artery occlusion, thrombosis due to hyperviscosity and thrombocytosis is
      mostly discussed as the origin of the infarction. We discuss the case of a 30
      year-old male patient, with polycythemia, who died of myocardial infarction. On
      autopsy the vessels showed neither ateriosclerotic changes nor thrombotic
      occlusions. Instead, a marked intima proliferation was found leading to multiple
      occlusions whereas media and adventitia were unchanged. This pattern of a
      coronary vasculopathy has not been described before, and can be interpreted as an
      alternative mechanism for vascular occlusion in polycythemia. Similar
      histopathological changes have already been found in skin lesions in
      erythromelalgia, a common symptom in polycythemia.

PMID- 9555120
TI  - Carcinoid tumor of the middle ear in a 28-year-old patient.
AB  - Carcinoid tumor of the middle ear is an extremely rare condition. The origin of
      the tumor cells is still speculative and the closeness of relationship to
      adenomas of the middle ear has been a matter of discussion since the first
      description of this tumor entity in 1980. In this study we report a case of a 28
      year-old male patient with a carcinoid tumor of the middle ear. We present the
      results of histomorphological, immunohistochemical and electron microscopic
      examinations and compare our findings to those of previously published cases.

PMID- 9555121
TI  - Intravenous leiomyomatosis of the uterus. A report of three cases.
AB  - Three cases of intravenous leiomyomatosis (IVL) of the uterus, a rare benign
      smooth-muscle tumor, are described. A preoperative diagnosis of IVL was not made
      in any of the patients, all of which presented with a pelvic mass with the
      presumptive diagnosis of leiomyoma. Surgical exploration confirmed the presence
      of uterine mass and two of the three cases showed extra-uterine extension into
      the ovarian or uterine veins. Histological examination demonstrated a fascicular
      pattern of bland spindle-shaped smooth-muscle cells, which extended to veins
      inside the myometrium or to extrauterine veins. This was confirmed by
      immunohistochemical stain for desmin and factor VIII. Despite their histological
      benignity, these lesions have a tendency to metastasize and are closely related
      to the conditions called "benign metastasizing leiomyoma" and "intracaval mass
      and cardiac extension". The primary treatment of IVL is hysterectomy and excision
      of any extrauterine tumor, when technically feasible. Anti-estrogenic therapy has
      been suggested as potentially useful in controlling of unresectable tumor.
      According to the literature, the follow-up must be long and periodic
      postoperative ultrasonic or magnetic nuclear resonance imaging studies may be
      useful in detecting growth of residual intravascular tumor.

PMID- 9555122
TI  - Plasma HIV-1 load and disease progression in HIV-infected patients in Hungary.
AB  - Nucleic Acid Sequence Based Amplification (NASBA) is a suitable method for the
      quantification of HIV-1 RNA in plasma and serum samples. Since determination of
      the viral load appears to be a valuable marker for the prediction of disease
      progression and for monitoring the efficiency of antiretroviral therapy, the
      National AIDS Committee initiated the introduction of NASBA in Hungary at the end
      of 1996. We obtained plasma samples from patients with ARC and AIDS of the Szt.
      Laszlo Hospital, Budapest. We found an increased viral burden in untreated AIDS
      (CDC group C) patients compared to untreated ARC (CDC group B) patients. In
      plasma samples of clinically stable ARC and AIDS patients treated with
      antiretroviral drugs we detected relatively low HIV-1 RNA copy levels while
      similarly treated ARC and AIDS patients with progressive disease had high HIV-1
      RNA copy numbers. The CD4+ T-cell count was lower in AIDS patients compared to
      ARC patients, as expected. In general, there was an inverse correlation (r = 
      0.487, P < 0.0001) between CD4+ T-cell counts and HIV-1 RNA levels. We concluded
      that measurement of HIV-1 RNA plasma level has an important role in assessing
      prognosis and effects of antiretroviral therapy in HIV-infected patients.

PMID- 9555123
TI  - Studies on the antibodies to human herpesvirus type 6 among Hungarian patients
      with asymptomatic HIV infection.
AB  - The occurrence and the possible role in promoting HIV infection by human
      herpesvirus type 6 (HHV-6) have not yet been revealed in Hungary. In different
      groups of patients, serum titre of IgM and IgG antibodies, as well as avidity of
      IgG were quantitated by indirect immunofluorescence and an enzyme-linked
      immunosorbent assay, using isolate U1102 of HHV-6 variant A as antigen. In 60% of
      HIV-seronegative adult controls, high avidity IgG antibodies were found in low
      titre suggesting childhood infection. In HIV-seronegative persons with high risk
      behaviour for HIV-infection, both IgM and low avidity IgG were frequently found
      in higher titre, representing either primary or frequent reinfections, or
      reactivation of latent HHV-6. In asymptomatic HIV-seropositive patients, high
      titre of high avidity IgG antibodies was predominant, proving virus infection in
      the near past. These results indicate the contribution of HHV-6 to
      immunosuppression prior to AIDS, predisposing the organism to HIV infection.

PMID- 9555125
TI  - [Diabetic gastroparesis: is tube feeding an alternative?].
AB  - A woman aged 26 with long-standing insulin-dependent diabetes mellitus displayed
      recurrent periods of nausea, vomiting, abnormal blood sugar levels, weight loss
      and poor physical condition in spite of a diet and use of propulsive agents.
      Scintigraphy revealed decelerated gastric evacuation for solid and liquid
      nutrients. The patient recovered after insertion of a percutaneous endoscopic
      gastrostomy (PEG) catheter. Diabetic gastroparesis is associated with a vicious
      circle in which delayed gastric emptying leads to poor glucose regulation with
      frequent hyperglycaemia, which in its turn adversely affects gastric emptying.
      Treatment should be aimed at improvement of the gastric motility (for instance by
      propulsive agents), more accurate glucose regulation and nutritional counselling.
      If this fails to produce improvement, tube feeding via a permanent nasoduodenal
      tube or via a PEG catheter constitutes an acceptable alternative for oral
      nutrition.

PMID- 9555124
TI  - Current concepts of tumor-induced angiogenesis.
AB  - Tumor induced angiogenesis is responsible for the nutrition of the growing tumor
      and can also increase the probability of hematogenous tumor dissemination. Data
      obtained from morphological analysis of tumor angiogenesis can contribute to the
      development of new anti-angiogenic therapies. Based on in vitro and in vivo
      observations several models of angiogenesis were introduced, explaining the
      mechanism of lumen formation and the timing of basement membrane depositon. (1)
      Lumen is formed either by cell body curving or by fusion of intracellular
      vacuoles of nonpolarized endothelial cells. New basement membrane is deposited
      after lumen formation. (2) Slit-like lumen is immediately formed by migrating
      polarized endothelial cells. Basement membrane is continuously deposited during
      endothelial cell migration, only cellular processes of the endothelial cell
      migrating on the tip of the growing capillary are free of deposited basement
      membrane material. (3) Development of transluminal bridges in larger vessels a
      process called intussusceptive growth leads to the division of the vessels. These
      models, however, describe angiogenesis in tissues rich in connective tissue.
      Different processes of angiogenesis take place in organs such as liver, lungs,
      adrenals, which are the most frequent sites of metastasis having high vessel
      density without sufficient space for capillary sprouting. In the case of liver
      metastases of Lewis lung carcinoma the proliferation of endothelial cells was
      elicited only by direct contact between tumor and endothelial cells, leading to
      the development of large convoluted vessels inside the metastases. These vessels
      were continuous with the sinusoidal system, suggesting that these metastases have
      dual blood supply. This observation, among others, is in contrast to the
      generally accepted view that liver tumors have arterial blood supply. The
      increasing number of data demonstrating the dual or venous blood supply of liver
      metastases should be taken into consideration in the therapy of liver metastasis.

PMID- 9555126
TI  - [Combination therapy in early rheumatoid arthritis: the COBRA study].
AB  - The scheme 'Combination therapy in rheumatoid arthritis' (COBRA) in early
      rheumatoid arthritis (RA) involves administration of not only sulfasalazine but
      also prednisolone and methotrexate during the first six months. The trial showed
      that the COBRA scheme over a period of 1.5 years was superior to sulfasalazine
      alone: less disease activity in the major part of the year of treatment, less
      articular damage on radiographs, fewer side effects and equal or reduced costs.
      An 'aggressive' treatment in patients with early RA is indicated, with
      (re)assessment of the use of corticosteroids.

PMID- 9555127
TI  - [Future developments in genetic research. I. Technological possibilities].
AB  - The attention in genetic research is shifting from the determination' of (rare)
      monogenic disorders to identification of genetic risk factors for important
      diseases at adult age. Mapping of all man's 80,000-100,000 genes will also
      provide more insight into the gene polymorphisms and mutations that are
      associated with various types of cancer, certain cardiovascular diseases,
      diabetes and neurodegenerative disorders, including Alzheimer dementia. Apart
      from new diagnostic possibilities, the DNA techniques create new prospects for
      the study of the pathogenesis of diseases and the devising of new strategies for
      treatment. Examples are familial hypercholesterolaemia, diabetes, breast cancer
      and colorectal carcinoma.

PMID- 9555128
TI  - [Future developments in genetic research. II. Psychological and social aspects].
AB  - Regarding the determination of genetic risk factors for serious diseases, the
      main question for a patient's young relatives is 'to know or not to know'. The
      answer depends among other things on the assessment of the severity of the
      disorder and the magnitude of the risk in relation to the population risk and on
      the availability of therapeutic or preventive measures. Experience with the
      requests for and the coping with results of the presymptomatic DNA test for
      untreatable neurodegenerative chorea of Huntington show that expectations about
      the effect of predictive DNA studies are often different from reality. A problem
      of a different nature arises in multifactorial diseases such as mammary or
      colonic carcinoma, because irrespective of the DNA study it remains uncertain
      whether or not the disease will occur. Nevertheless more than half of the healthy
      relatives of a patient with breast cancer requests DNA testing and a large
      majority of the proven carriers of a BCRAI and BRCA2 mutation chose for bilateral
      mastectomy and oophorectomy. Many questions about psychosocial consequences of
      predictive DNA testing remain to be answered: what will be the effect of early
      medicalization, how will relations be affected and which effect will carriership
      of genetic risk factors have on behaviour? Dutch legislation provides adequate
      guarantees against the use by third parties of results of genetic testing. The
      question remains, however, how future internationalization will work out in this
      respect. The possibly far-reaching social and psychological consequences of
      genetic research make some people feel that restraints should be imposed on this
      research. However, there are more grounds for curiosity and enthusiasm to
      constantly find new solutions for the new problems.

PMID- 9555129
TI  - [End of life and termination of life: opinions of elderly persons with health
      problems].
AB  - OBJECTIVE: To determine the views of elderly persons with physical limitations
      about a number of aspects of the end stage of life and termination of life.
      DESIGN: Enquiry. SETTING: University of Groningen, the Netherlands. METHOD: An
      enquiry was conducted in 1995 among 575 elderly (429 females, 146 males; age 57
      99 years; 281 living alone) with physical restrictions (mostly heart disease,
      hypertension, rheumatism or other articular diseases). The group had been
      selected from the 'Groningen longitudinal aging study'. The respondents were
      asked (a) what they thought about euthanasia, (b) whether they worried about the
      end stage of life, (c) whether they were afraid of death and how much they were
      'preoccupied with death'. For the last-mentioned two questions a visual analogue
      scale was used. RESULTS: Almost one-third of the elderly were not preoccupied
      with death and over half were not afraid of death. Very few scored high on these
      scales. Respondents' views about the acceptability of active termination of life
      varied greatly: almost half were of the opinion that their life had to be
      terminated once they themselves had developed complete dementia. Regarding the
      end stage of life, respondents mostly worried about being a burden to others,
      being completely dependent on others, having to say goodbye to their loved ones
      and having to suffer greatly. Elderly persons with poorer health were more
      preoccupied with death and worried more about the problems of the end stage of
      life. CONCLUSION: Most of those interviewed were not greatly preoccupied with or
      afraid of death. They did worry, however, about the problems that might be
      associated with the end stage of life.

PMID- 9555130
TI  - [Psychiatric morbidity among adults in The Netherlands: the NEMESIS-Study. I.
      Objectives, design and methods. Netherlands Mental Health Survey and Incidence
      Study].
AB  - OBJECTIVE: To determine prevalence, incidence and course of psychiatric disorders
      in non-institutionalised Dutch adults. DESIGN: Prospective and cross-sectional.
      SETTING: Trimbos Institute, Utrecht, the Netherlands. METHOD: A multistage,
      stratified random sampling procedure was used to obtain a sample of 7076 adults
      (18-64 years). Respondents were interviewed throughout 1996 in their homes. The
      main diagnostic instrument was the 'Composite international diagnostic interview'
      (CIDI), designed to assess lifetime prevalence of mental disorders according to
      Diagnostic and statistical manual of mental disorders, 3rd revised edition (DSM
      III-R). The diagnostic categories were: affective disorders, anxiety disorders,
      eating disorders, schizophrenia and other non-affective psychoses, and substance
      use disorders (dependence and abuse). The sample was weighted towards national
      census data on sex, age, marital status and urbanicity. RESULTS: The results of
      the first measurement (1996) will be described in the next article (1997:2353
      60). The response rate was 64.2%. There were no indications that the psychiatric
      morbidity of non-respondents differed from respondents. The same respondents will
      be interviewed again after 12 (1997) and after 36 months (1999).

PMID- 9555131
TI  - [Psychiatric morbidity among adults in The Netherlands: the NEMESIS-Study. II.
      Prevalence of psychiatric disorders. Netherlands Mental Health Survey and
      Incidence Study].
AB  - OBJECTIVE: To determine the prevalence of psychiatric disorders in non
      institutionalised Dutch adults. DESIGN: Cross-sectional. SETTING: Trimbos
      Institute, Utrecht, the Netherlands. METHODS: A representative sample of 7076
      adults (18-64 years) in the Netherlands' population were interviewed in 1996 to
      determine the prevalence of mental disorders ever, in the previous 12 months and
      in the previous month. Objectives and study design are described in the previous
      article (1997: 2448-52). The 'Composite international diagnostic interview'
      (CIDI) was used to assess the following mental disorders according to Diagnostic
      and statistical manual of mental disorders, 3rd revised edition (DSM-III-R):
      affective disorders, anxiety disorders, eating disorders, schizophrenia and other
      non-affective psychoses, substance dependence and substance abuse. RESULTS:
      Mental disorders were common in the general population: the prevalence 'ever' of
      all disorders was 41.2%, the 12-month prevalence 23.5%, without sex differences.
      Depression, anxiety disorders and alcohol abuse and dependence showed high
      prevalence and comorbidity. The prevalence 'ever' of schizophrenia and other non
      affective psychoses was low (0.4%).

PMID- 9555132
TI  - [Cerebral hyperperfusion syndrome following carotid endarterectomy].
AB  - Three patients with a severe symptomatic carotid stenosis developed headache,
      epileptic seizures and focal neurologic deficits several days after carotid
      endarterectomy. CT of the brain revealed hypodensities, indicative of cerebral
      oedema with haemorrhagic components. This is caused by cerebral hyperperfusion, a
      complication after carotid endarterectomy as a result of increased cerebral
      perfusion on the side of the operated carotid stenosis. Dysfunction of the
      cerebral autoregulation believed to be the cause of this hyperperfusion.
      Sometimes these complications are incorrectly attributed to one of the better
      known types of stroke.

PMID- 9555133
TI  - [Peritoneal pseudomyxoma].

PMID- 9555134
TI  - [Current developments in preventive health care].

PMID- 9555135
TI  - [Pain control in the end stage of life].

PMID- 9555136
TI  - [Pain control in the end stage of life].

PMID- 9555137
TI  - ['Tramps feet' in vagrants].
AB  - The lifestyle of the homeless often implies lack of hygiene resulting in -
      neglected - feet pathology. The Public Health department for the homeless (GG&GD)
      was visited by a man aged 43 with drug addiction and schizophrenia who suffered
      from severe 'tramp's feet' complicated by cellulitis of the right lower leg,
      which had not been diagnosed adequately during a previous visit to an emergency
      department. Adequate antibiotic treatment improved the condition in a few days.
      'Maladjusted' presentation of the homeless may lead to hasty, inadequate
      judgement and treatment by health care workers. These socially handicapped
      patients need proper physical examination and efforts to realise shelter, care
      and indicated treatment.

PMID- 9555138
TI  - [Prasterone (dihydroepiandrosterone): a modern source of eternal youth?].
AB  - The function of adrenal cortical hormone dihydroepiandrosterone (DHEA) is
      currently unknown. The use of this hormone as a food supplement is widely
      recommended in the USA for the elderly, as DHEA serum concentrations decrease
      dramatically after the age of about fourty. DHEA is available without
      prescription. Many sources suggest a causal relation between the decrease of DHEA
      production during aging and the emergence of degenerative disorders. To
      substantiate this relationship animal experimental and epidemiological literature
      is cited. However, data from clinical trials are rare and neither the safety nor
      the efficacy of DHEA is documented. Via the modern media such as the Internet the
      consumer is stimulated to use and order DHEA, 'the fountain of youth'. Consumers
      willing to follow this recommendation should be informed about the absence of
      proof of safety and efficacy. However, the compelling suggestions from animal and
      epidemiological literature of DHEA activity are intriguing, and further clinical
      trials to document the efficacy and safety of DHEA are urgently needed.

PMID- 9555139
TI  - [Prevalence of discrepant lipid levels in Curacao].
AB  - OBJECTIVE: To assess the prevalence of lipid risk factors in Curacao and to
      investigate possible interactions with socioeconomic and demographic variables.
      DESIGN: Cross-sectional population-based study. SETTING: Public Health Laboratory
      and Public Health Service, Curacao, Netherlands Antilles. METHODS: In a random
      sample of persons aged 18 years and over from the population of Curaao, serum
      levels were measured of total cholesterol, high-density lipoprotein (HDL)
      cholesterol, triglycerides and, in a smaller number of samples, of lipoprotein(a)
      (Lp(a)). The findings were in persons between 20 and 60 years compared with those
      reported for a random sample from the Netherlands. Multiple regression analysis
      was used to study the relationship between the total cholesterol values found and
      various socio-economic variables (age, sex, education, place of residence, race).
      RESULTS: Among persons aged 20-59 years serum cholesterol levels were > 6.5
      mmol/l in 30 of the 288 male participants (11%) and in 42 of the 427 female
      participants (10%). Fifty-three of the males (18%) had HDL cholesterol levels <
      0.9 mmol/l as against 31 of the females (7%). The distributions of both total
      cholesterol and HDL cholesterol levels was better in Curaao than in the
      Netherlands, among males aged 20-29 years and males and females over 40 years of
      age. The median Lp(a) concentration of the 225 participants of Curaao in whom it
      was measured was 250 mg/l, as against 80 mg/l in the Dutch group. More advanced
      age, female sex, higher educational level, negroid race and residence in the
      'East District' were correlated with a higher serum level of total cholesterol.
      CONCLUSIONS: Both total cholesterol and HDL cholesterol concentrations were
      favourable in Curacao compared with the Netherlands, especially in the elderly
      population.

PMID- 9555140
TI  - [Risk factors for a complicated disease course in children with measles admitted
      to a Philippine university hospital].
AB  - OBJECTIVE: To analyse the correlation of specific risk factors and measles
      complications in children admitted to a Philippine university medical centre.
      DESIGN: Retrospective cross-sectional study. SETTING: Department of Pediatrics,
      De La Salle University Medical Center at Dasmarinas, a suburb of Manila, the
      Philippines. METHOD: Information was collected on patients under 16 admitted for
      measles from January 1993 to May 1996, using a data collection form. RESULTS: Of
      the 180 patients included in this study, 8 (4%) died during the hospital stay,
      and 172 left the hospital in good condition. 61 Patients (34%) had complicated
      measles (pneumonia, gastroenteritis, and (or) encephalitis). Age under 2 years
      and stay in the service ward (as opposed to the private ward) were significantly
      related to complicated measles. No significant relation was found for the
      presence of associated illnesses or malnutrition. CONCLUSION: More severe
      complications were seen at an early age than in industrialised countries where
      the frequency appears to increase with age. Malnutrition possibly contributes
      less to severity of the disease than environmental factors such as hygiene and
      social class.

PMID- 9555141
TI  - [Harlequin syndrome].
AB  - Harlequin syndrome is an autonomic syndrome of heat, emotion and exercise induced
      flushing and sweating limited to one side of the face in combination with
      impairment of sweating and flushing on the contralateral side, Two women aged 32
      and 39 years displayed this syndrome. In one patient no other neurological
      symptoms were found; MRI of cervicothoracic spine failed to disclose a structural
      lesion. The second patient had four years before presented with a Horner's
      syndrome on the contralateral side, where MRI now disclosed a tumour located in
      the paravertebral thoracic region at the apex of the lung.

PMID- 9555142
TI  - [Toe tourniquet syndrome].
AB  - In two boys aged 4 months and one girl aged 2 months one or two toes were red and
      oedematous, while in one boy aged 3 weeks one toe had become necrotic. In the
      first-mentioned three children the affected toes were encircled by a hair, the
      hair was removed under anaesthesia, after which the children recovered. In the
      last-mentioned child, amputation through the proximal phalanx was necessary. The
      toe tourniquet syndrome occurs mainly in infants. Strangulation of the toes by
      circular foreign material. such as hair or fibre, causes oedema and increasing
      constriction. Timely treatment is followed by good recovery. Delayed or
      incomplete treatment can lead to necrosis which may necessitate amputation.

PMID- 9555143
TI  - [The first Nassaus in The Netherlands: identification of and paleopathological
      findings in Willem van Oranje's ancestors, buried in the Grote Onze Lieve Vrouwe
      Kerk in Breda].
AB  - OBJECTIVE: Identification and paleopathological analysis of the remains of the
      first members of the Nassau dynasty in the Netherlands. DESIGN: Descriptive.
      SETTING: Centre for Physical Anthropology 'Barge's Anthropologica', Leiden
      University. METHODS: In 1996, seven interments were discovered in situ in a tomb
      under the Nassau monument of the so-called 'Grote' or 'Onze Lieve Vrouwe' Church
      of the city of Breda. The interments were excavated and examined by osteological
      analysis, X-ray analysis, accelerator mass spectrometry (AMS) 14C dating of bone
      and dendrochronological dating. RESULTS: Evaluation of archaeological,
      osteological, dendrochronological and AMS 14C-dating data resulted in
      identification. in order of death, of: Engelbrecht I van Nassau (ca. 1370-1442
      AD), Johanna van Polanen (1392-1445 AD), Jan IV van Nassau (1410-1475 AD),
      Cimburga van Baden (1450-1501 AD), Maria van Loon (1425-1502 AD), Engelbrecht II
      van Nassau (1451-1504 AD) and Francoise van Savoye ((1480-1486)-1511 AD).
      Remarkable medical findings were: embalming procedures employed (skull cap
      detachment, removal of viscera), treponematosis (Engelbrecht II), tumour
      metastases (Jan IV) and scoliosis (Francoise van Savoye). CONCLUSION: The methods
      employed resulted in positive identification of the first members of the Nassau
      dynasty in the Netherlands and diagnoses of their paleopathological changes.

PMID- 9555144
TI  - [Jan Steen's fire pot; pregnancy test or gynecological therapeutic method in the
      17th century?].
AB  - The doctor's visit is a frequently used subject in paintings from the 17th
      century. Jan Steen made several paintings in this genre. He always used as a
      medical attribute a fire pot with a burning lace. This lace can be explained as a
      diagnostic tool for pregnancy, as a medium to bring round a fainting woman--or
      (and most probably) as a scent therapy for a wandering womb. This therapy
      originates from the Egyptians and antique Greek doctors.

PMID- 9555145
TI  - [Penicillin: just in time].
AB  - In the attic of his home the author found papers concerning the case history of a
      woman who in the first days after the liberation, in April-May 1945, suffered
      from a severe form of puerperal sepsis. The woman recovered completely after
      treatment with a totally new drug: penicillin, obtained from the medical supplies
      of the allied British forces. She probably was the first patient treated with
      this antibiotic in the Netherlands.

PMID- 9555146
TI  - [Stranger in Turkey].
AB  - The author, a professor of nephrology, reports some impressions of his 7-year
      stay in Turkey. He worked at the Ege University in Izmir, traditionally one of
      the most 'western' cities. He and his wife, who gave unpaid assistance to
      dialysis patients, attempted to integrate into Turkish society as fully as
      possible. They traversed the country in weekends and holidays and introduced as
      many Dutch guests as they could to the unique archeological treasures, the
      magnificent nature and the extremely friendly population. Work at the university
      focused increasingly on cultivating a critical attitude with regard to the self,
      society and the trends and commercialization of medicine in Turkey and in the
      rest of the world. Self-reliance, also, had to be strengthened. Although this
      contravened the authority-based Turkish educational system, the efforts were
      clearly appreciated and even stirred enthusiasm in many of the younger people.
      There is no doubt that a foreign worker is regarded much more favourable in
      Turkey than in the Netherlands.

PMID- 9555147
TI  - [When is the morning-after pill indicated and which application is preferable?].

PMID- 9555148
TI  - [Excessive terfenadine level caused by drinking grapefruit juice].

PMID- 9555149
TI  - [Excessive terfenadine level caused by drinking grapefruit juice].

PMID- 9555150
TI  - [Eye paralysis and confusion].
AB  - Two patients, women of 85 and 76 years, presented with horizontal ocular paresis.
      The first patient had a palliative ileocecal resection for adenocarcinoma with
      metastases and developed the ocular paresis only after intravenous glucose
      infusion. The second had chronic haemolytic anaemia and weight loss due to
      malnutrition. The two women were also confused. In both patients acute Wernicke's
      encephalopathy was diagnosed, caused by thiamine deficiency. The disorder could
      easily have been missed because of confounding clinical problems. Early treatment
      of Wernicke's encephalopathy (thiamine 100 mg/day intramuscularly for 3 days) is
      of major importance in preventing permanent neurological damage or even death.

PMID- 9555151
TI  - [A cholesterol reducing diet is not useful].
AB  - In daily practice a cholesterol-lowering diet with intensive monitoring by
      dieticians leads to a mean decrease of the serum cholesterol level by 2%. Once
      the monitoring is discontinued, the serum cholesterol level as a rule returns to
      baseline. Were it possible to maintain a 5% cholesterol reduction throughout
      life, occurrence of coronary heart disease would in theory be postponed by one to
      a few months. In diet studies, with observation lasting from 6 to 15 years, no
      clear favourable effect on the development of coronary heart disease was
      demonstrated. Prescription of a cholesterol-reducing diet and referral to a
      dietician are therefore fairly useless.

PMID- 9555152
TI  - [Cholesterol reducing food certainly is useful].
AB  - The effect of a low-cholesterol diet in open intervention studies depends in the
      long run on motivation, knowledge and dedication. The mean decrease of the serum
      cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies
      clearly prove a connection between the intake of saturated fat, the serum
      cholesterol level and the risk of coronary heart disease and death. High-fat food
      slows down the clearance of the degradation products rich in cholesterol which
      appear in the blood after a meal and which are highly atherogenic (these products
      are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has
      additional useful effects, for instance on the blood pressure and the
      coagulation. The recommendations for healthy, low-cholesterol nutrition for the
      population as a whole apply particularly to patients with a high risk of coronary
      heart disease. Although advice given to individuals often has a disappointing
      effect, influencing the life pattern should be included in the strategy to reduce
      the risk of coronary heart disease.

PMID- 9555153
TI  - [Value of determining serum cholesterol levels in patients with coronary heart
      disease].
AB  - Cholesterol synthesis (HMG-CoA reductase) inhibitors have proven their value in
      preventing cardiovascular events, especially in patients with manifest coronary
      heart disease. Besides cholesterol lowering a number of effects have been
      described which may contribute to the beneficial influence of these agents on the
      process of atherosclerosis. Measurement of serum lipids is still necessary for
      various reasons, namely, to know the degree of elevation in serum cholesterol and
      specific disturbances in lipid metabolism, the extent to which serum lipids must
      be lowered and the compliance with cholesterol lowering therapy.

PMID- 9555154
TI  - [Is detection and treatment of familial hypercholesterolemia indicated in
      children?].
AB  - Familial hypercholesterolaemia (FH) is a congenital metabolic disorder
      predisposing to severe atherosclerosis resulting in coronary heart disease
      sometimes even at early adult age. Children with FH lack the stigmata at physical
      examination and measuring the cholesterol level does not always enable the
      clinician to make the diagnosis. In about 70% of the cases, the diagnosis of FH
      in childhood can be made by means of molecular-biological examination, by
      demonstrating the underlying defect of the LDL cholesterol receptor gene. In the
      remaining cases, the combination of the positive family history for
      cardiovascular diseases and increased total cholesterol and LDL cholesterol
      levels should suggest the diagnosis of FH. Pharmaceutical agents inhibiting the
      cholesterol synthesis have been researched very little in children and are not
      registered in the Netherlands. Nevertheless, drug treatment of children with FH
      is advisable because of the better possibilities to make a definite diagnosis and
      the early occurrence of coronary heart disease. If this treatment were indicated
      before patients reach adult age, the question arises whether screening for FH of
      children in families in which this disorder prevails, should not be promoted more
      strongly.

PMID- 9555155
TI  - [Is the detection of familial hypercholesterolemia in children indicated?
      Occasionally, yes].
AB  - Searching for familial hypercholesterolaemia (FH) in children is useful only if
      efficacious treatment is to be administered shortly and if there are relatives
      with ischaemic heart disease at very early ages. In all other cases, the
      (psychological) drawbacks probably outweigh the doubtful benefit of early
      intervention. The search for the major homozygous form of FH begins with
      cholesterol assay in both parents, in the absence of FH in either of them, the
      above-named restrictions apply.

PMID- 9555156
TI  - [Nobel Prize of Medicine 1997 awarded for prion theory].
AB  - The Nobel Prize 1997 for Medicine and Physiology was awarded to S.B. Prusiner,
      who proposed the prion hypothesis. Prions are small 'proteinaceous infectious
      particles' that lack nucleic acids and hence genetic information. Prions are
      normal host encoded proteins but with an abnormal tertiary structure, which makes
      them extremely resistant to chemical and physical inactivation that would modify
      nucleic acids. They 'replicate' by forcing their conformation upon the normal
      prion proteins. Recently it was demonstrated that the prion disease, bovine
      spongiform encephalopathy (BSE) can be transmitted to man in whom it causes a new
      variant of Creutzfeldt-Jakob disease.

PMID- 9555157
TI  - [Molecular biology diagnosis of tumors of the musculoskeletal system].
AB  - It is sometimes difficult to make an unequivocal diagnosis of tumours of bone and
      soft tissue based upon classical morphology alone, which has led to an increased
      use of additional diagnostic tools. In the past decade new techniques have become
      available, based on tumour specific genetic alterations, for instance chromosomal
      translocations. With the cloning of the translocation breakpoints and the
      identification of the genes involved, the reverse transcriptase polymerase chain
      reaction (RT-PCR) detection of the fusion gene has become an important diagnostic
      test. Also, non-tumour specific genetic alterations with prognostic value can be
      detected.

PMID- 9555158
TI  - [Revision consensus hemophilia: treatment and responsibility. Nederlandse
      Vereniging van Hemophilia Patients].
AB  - Haemophilia is an X-linked clotting disease occurring in 1400 men in the
      Netherlands. As the result of factor VIII or IX deficiency, haemophilia patients
      suffer from severe bleedings, spontaneous or caused by trauma. Bleedings mostly
      occur in major joints and muscles. Repeated bleedings can cause disability.
      Treatment of haemophilia consists of replacement therapy with factor VIII or IX.
      The first aim of treatment is to prevent bleedings (prophylaxis). The second aim
      is to limit joint damage in case of bleeding by timely and adequate substitution
      therapy. In addition, physical therapy and sports are used to keep patients in
      shape. Until the introduction of recombinant factor VIII in 1992 only plasma
      derived factor VIII and IX products were available. Substitution therapy has
      caused various side effects, such as allergic reactions. Since the introduction
      of ultra-pure concentrates, allergic reactions have grown rare. Viral infections
      like HIV and hepatitis C, which were transmitted through blood products, have not
      occurred in Dutch haemophilia patients since the introduction of adequate viral
      inactivation steps. In case of development of antibodies against factor VIII or
      IX, therapy with factor VIII or IX products is insufficient. Antibody formation
      is more often seen in haemophilia A (25%) than in haemophilia B (2%). In most
      cases antibodies disappear during so-called immune tolerance induction. This
      therapy consists of regular infusion with factor VIII or IX. Once an inhibitor
      has disappeared, patients can be treated normally once more. As haemophilia is a
      rare and complex disease patients should be treated in specialized centres,
      preferably by a comprehensive care team. This is even more justified because
      treatment of haemophilia is costly. Over the last 20 years haemophilia treatment
      has improved much. This has resulted in a decrease of the number and of the
      duration of hospitalization, and a decrease in days lost at school or work. This
      has led to great improvement of the social life of haemophilia patients.

PMID- 9555159
TI  - [Hyperthyroidism due to contamination of the alternative drug Ader-Rein (Vascu
      Vitaal)].
AB  - A 52-year-old woman developed hyperthyroidism due to the alternative Vascu-Vitaal
      pills. She was suffering from nephrotic syndrome due to membranoproliferative
      glomerulonephritis and subclinical hypothyroidism, possibly due to renal loss of
      thyroid hormone. For peripheral vascular disease she took the non-registered
      Vascu-Vitaal pills on her own initiative. According to the product information,
      these pills contain multiple vitamins, minerals, amino acids and tissue extracts
      of bovine adrenals, hypophysis and thymus. The patient developed hyperthyroidism
      after starting on a new batch of the preparation; it subsided after stopping the
      treatment. A technetium thyroid scan showed decreased uptake and subsequently the
      Vascu-Vitaal pills were found to contain both thyroxine and triiodothyronine. The
      thyroid hormone contamination was probably caused by bovine thyroid tissue. It is
      suggested to require a health warning statement on the package of alternative
      therapeutics stating that production and contents are not subject to governmental
      supervision.

PMID- 9555160
TI  - [Medical education of tomorrow: a glance into the (near) future].
AB  - Educational reform is a topical subject in Dutch medical schools. Public
      visitation reports were issued in 1992 and 1997. In 1994 an 'outline plan' was
      presented, setting forth communal training requirements (final results). An
      important consequence will be reorganization of (assistant) housemanships.
      Options are to start already in the 3rd- and 4th-year with a few (assistant)
      housemanships, to reduce the number but increase the duration of the (assistant)
      housemanships and to introduce a more comprehensive training (including elements
      from several disciplines). Other areas for special attention are the insufficient
      professionalization of teachers in medicine, the bureaucracy weighing down the
      teaching and the continuing need of educational research. Regarding the future
      doctors' image of their profession, emphasis should be placed on the
      international trend toward more attention for prevention and cost control, apart
      from the physician's traditional curative task. With respects to curriculum
      reorganization, six items should be considered: the need of a basic philosophy
      (per faculty), the priority to be given to the process of medical problem solving
      over that of acquiring knowledge and information, the desirability of increasing
      orientation to practice, the necessity of an integrated approach of medical
      teaching (teaching elements to be deduced from the final terms, instead of vice
      versa), development of a professional attitude and the realization of a master
      apprentice relationship in medical education.

PMID- 9555161
TI  - [Contemplating a university clinical department].
AB  - University clinics combine teaching, research and patient care. Some think that
      no single person (head of department) can perform all three tasks. Also, the head
      has to have the political skills necessary to manage the faculty society. The
      guidelines for university clinics, and for their heads in particular, are: (a)
      conscious pursuit of optimal quality, (b) giving the highest priority to training
      house staff and teaching students, (c) providing patient care and (d) ensuring
      that clinical research should serve the purpose of inspiring scientific attitudes
      in house staff. The 'product' of a university clinic is neither the sum of its
      publications nor the cured patient, but the medical specialist delivered to
      society.

PMID- 9555162
TI  - [Multidisciplinary treatment of cerebral arteriovenous malformations: preliminary
      results in 115 consecutive patients].

PMID- 9555163
TI  - [Boron neutron capture a a new radiotherapy model].
AB  - The boron neutron capture therapy is based on the reaction occurring with certain
      probability, if a thermal neutron meets the boron 10 isotope. The low energy slow
      neutron is captured by the nucleus and it disintegrates into Li-nucleus and He
      nucleus (alpha particle). If this physical reaction occurs in a living cell that
      will be destroyed. If the boron neutron capture reaction could be achieved
      selectively in malignant cells of tumor patients, that could be an effective
      therapeutical modality to treat the locally growing cancers. For boron neutron
      capture therapy to be successful two basic conditions must be fulfilled, an
      appropriate neutron source must be available and the sufficient number of 10B
      must be delivered possibly selectively into the tumor cells by a boron compound.
      At present both part of this binary system are under intensive investigation, the
      development of the neutron source, the synthetisation and experimental testing of
      boron delivery agents. The development of the dosimetry, microdosimetry, the work
      out of the powerful tools of detection the cellular, subcellular 10B
      distribution, the continuous improvement of the planning system and the
      optimization of the boron neutron capture therapy are the main point of the
      research area on boron neutron capture therapy. Clinical studies and clinical
      application of boron neutron capture therapy are under way for the treatment of
      melanoma malignum and for brain tumors, with the two boron compound has been
      clinically tested up to now, in Japan, at two Centres in USA, and recently has
      been started in Europe. The authors give an overview about the principles of
      boron neutron capture therapy, about the result of the research on neutron
      sources and boron compounds, moreover about the possible application area of this
      new radiation modality.

PMID- 9555164
TI  - [Incidence of septal aneurysm and its clinical significance].
AB  - The authors performed 451 transesophageal echocardiographic (TEE) investigations
      over a period of three years and four months. Atrial septal aneurysm (ASA) was
      found in 40 cases. Of these, protrusion of the atrial septum towards the right
      atrium was observed in 17 cases, whilst oscillation of the atrial septum was
      noted in 23 cases. ASA was associated with patent foramen ovale (PFO) in ten
      patients, with type II. ASD in nine patients, with other congenital heart disease
      in six patients, and with other organic heart disease in eight patients. In three
      cases either an embolus or a tumor was detected in the left atrium, whilst in
      four cases with ASA there were no other organic cardiac disorders found. In ten
      patients there was a history of cerebral embolisation. Of these two had chronic
      atrial fibrillation, whilst the others had sinusrhythm. Of those who had cerebral
      embolisation, four patients had PFO, one patient had left atrial and auricular
      thrombi, whilst in four patients various organic heart problems (ischemic heart
      disease, left ventricular hypertrophy) were detected. In one patient with ASA
      there was no other cardiac abnormality detected. The authors conclude that ASA,
      which is often associated with PFO and ASD (in 25.0% and 22.5% of their cases,
      respectively) is detected in around eight percent of the patients who undergo
      TEE. ASA particularly when associated with PFO should be considered as a
      potential source of cerebral emboli. Indeed, cerebral embolisation occurred in
      25% of their patients with ASA. It is recommended, that patients with ASA are
      treated with acetyl salicylic acid, whilst in patients with ASA and PFO
      anticoagulant therapy is the treatment of choice. In case of cerebral
      embolisation, or repeated cerebral ischemic attacks, operative interventions
      should be considered.

PMID- 9555165
TI  - [Juvenile aneuploid papillary cancer of the thyroid with pulmonary metastasis].
AB  - The long-term cause-specific survival results of papillary thyroid cancer
      patients in Hungary are (78%) worse than the best international data (90%). The
      authors have recited its causes through the case of a young papillary thyroid
      cancer patient during the diagnostics (aspiration cytology, diagnostic imaging
      technics, DNA-analysis) the treatment (surgery-external radiotherapy-radioiodine
      treatment) and the follow-up (HTG, diagnostic imaging).

PMID- 9555166
TI  - [The role of vaginal smears in the follow-up od menopausal symptoms].
AB  - The author analyzed the data of 122 climacteric patients, getting a fix
      combination, continuous hormone replacement therapy, having an initial, a 6 month
      and a 12 month vaginal hormone smear and telling the opinion on the efficacy of
      the treatment. According to the data, the author registered a significant
      improvement of the climacteric complaints after a 6 month treatment period. The
      author considers the vaginal hormone smear an easy and effective method to follow
      the hormonal state of the climacteric patients. It is advisable to spread this
      procedure more widely, than it is to day.

PMID- 9555168
TI  - [Pal Salacz M.D., (1897-1971)].

PMID- 9555167
TI  - [Angiolymphoid hyperplasia with eosinophilia].
AB  - The authors describe the case of a 38-year-old female patient suffering from
      angiolymphoid hyperplasia with eosinophilia. The symptoms, histopathology,
      differential diagnostic relations and the therapeutic modalities of this disease
      are discussed.

PMID- 9555169
TI  - [Zsigmond Szerb, M.D., internist and dietitian].

PMID- 9555170
TI  - [Conditions of public health during the 1848/49 War of Independence in Hungary].

PMID- 9555171
TI  - [The Medical Review of Liege].

PMID- 9555172
TI  - [The 1998 cover of the Medical Review of Liege: histoplasmosis in an AIDS
      patient].

PMID- 9555173
TI  - [Drug clinics. How I treat cutaneous melanoma].
AB  - Skin melanoma is one of the rare cancers whose prevalence has increased over the
      past decades. Its treatment is based on a classification into four
      anatomoclinical stages. Surgical excision is the mainstay of therapy. However,
      several protocols of chemotherapy, radiotherapy and immunotherapy also have
      specific indications in the therapeutic or palliative approach to the disease.

PMID- 9555174
TI  - [The clinical case of the month. Apropos of a case of unexplained fever].
AB  - An episode of fever of prolonged duration and undetermined origin always remains
      a difficult clinical problem. Several etiologies can indeed be responsible. If
      one wishes to obtain a diagnosis of the origin of the fever, one should adopt a
      well-structured strategy in which the various investigations are carried out in a
      strictly determined hierarchical order. This is badly needed if one wishes to
      reach a clue to the diagnosis and be able to implement an adequate therapy. In
      spite of all this, some cases will remain without precise diagnosis. The
      treatment of those cases will primary be empirical.

PMID- 9555175
TI  - [Medical disorders which interfere with pregnancy].
AB  - During pregnancy, the future mother can develop several different diseases. Most
      of them have a benign prognosis. Cyanotic heart disease, at least when it is
      accompanied by significant pulmonary hypertension or induces a functional class
      IV represents a contra-indication to pregnancy. Pregnancy cardiomyopathy
      generally carries a poor prognosis and may be responsible for the mother's death.
      Herpes virus pneumopathy can also be extremely dangerous. Lupus erythematosus
      represents a factor of guarded prognosis for the outcome of pregnancy;
      discontinuation of the latter should be seriously considered. Hepatic steatosis
      which is a rare diagnosis must be distinguished from Hellp syndrome in which the
      maternal prognosis is much better. In this review, we shall briefly discuss
      various medical diseases which may have a deleterious influence on the evolution
      of pregnancy or on the foetus. These deleterious influences can be direct, i.e.
      due to the disease, or indirect, i.e. due to the therapy. We shall successively
      consider several neurological, cardiological, pulmonary, dermatological and
      digestive diseases. We shall not take into account viral infections or infections
      in general, diabetes mellitus or the various vasculo-renal syndromes.

PMID- 9555176
TI  - [Implementation of oral rehydration in gastroenteritis in infants].
AB  - The best treatment of the infant acute gastroenteritis, when it is applied at
      home, is oral rehydration. The latter should be limited in duration (between 12
      to 24 hours at the longest), should be performed with a specifically prepared
      solution, should be administered in sufficient amount and should be followed with
      an early realimentation.

PMID- 9555177
TI  - [Drug clinics. Clinical drug trials: the importance and role of the general
      practitioner].
AB  - Clinical trials are an essential step in the development of a drug. They must be
      conducted according to strict rules called "Good Clinical Practice" or GCP. GCP
      requirements aim to guarantee a perfect methodology in the planning, realization
      and interpretation of clinical trials. The latter can be divided in four phases:
      phase 1 aiming to demonstrate the safety and to investigate the
      pharmacokinetics/metabolism of the drug in healthy volunteers; phase 2 aiming to
      study the intrinsic activity (generally versus a placebo) and safety of the
      compound in a rather small number of (hospitalized) patients; phase 3 aiming to
      confirm the comparative efficacy (versus a placebo or a reference drug) and
      safety of the pharmacological agent in a quite large number of (ambulatory)
      patients; and phase 4 carried out after commercialization, to verify the clinical
      utility of the drug in conditions of daily practice. Because he/she occupies a
      crucial position in the recruitment and follow-up of outpatients, the general
      practitioner should play a more active role in clinical trials, provided that
      he/she could work in collaboration with academic centers specialized in clinical
      pharmacology which can help to perform studies in accordance with GCP
      requirements.

PMID- 9555178
TI  - [Lipoma, multiple lipomas and lipomatosis].
AB  - Lipomatous tumors are very frequent; simple lipoma is the most common variety.
      According to Enzinger, lipomatous tumors are classified into five different
      groups: simple lipomas, variant lipomas forms, heterotopic lipomas, infiltrating
      lipomas and lipomatosis, and finally hibernomas. Usually, lipomatous tumors are
      characterized by a slow, unpainful, growth. Classical treatment includes surgical
      resection. The clinical diagnosis is confirmed by histology. Liposucion can be a
      therapeutic option in certain cases.

PMID- 9555179
TI  - [Alcohol, drugs, medication and highway safety in Belgium. Belgian Toxicology and
      Trauma Study Research Group].
AB  - The BTTS study (Belgian Toxicology and Trauma Study) was performed in Belgium
      between January 15th 1995 and June 15th 1996. The purpose was to investigate how
      frequently the drivers involved in road accidents were driving under the
      influence of psychotropic drugs. Two thousand fifty-three blood tests were
      performed of which 207 in the Liege region. The results obtained at the national
      level are compared to those obtained at the level of the Liege region. In both
      cases, the BTTS study allows the conclusion that a considerable proportion of
      drivers involved in road accidents resulting in significant traumatic
      consequences were driving under the influence of substances with psychotropic
      properties.

PMID- 9555180
TI  - [Syndrome X, at the crossroads of metabolic and cardiovascular diseases].
AB  - The relationships between metabolic disorders and cardiovascular diseases are
      very strong. Hypercholesterolaemia and diabetes mellitus, for instance, are well
      known risk factors. The multifaceted metabolic syndrome or syndrome X, originally
      described by Reaven in 1988, comprises several abnormalities which are associated
      to insulin resistance and compensatory hyperinsulinaemia. Syndrome X results in
      an increased vascular risk by at least two mechanisms. On the one hand, it
      favours atherosclerosis and is associated to angiographic lesions, especially in
      the coronary arteries. On the other hand, it is associated to endothelial
      dysfunction which may contribute to myocardial ischaemia even in presence of
      angiographically normal arteries, a phenomenon named also syndrome X by the
      cardiologists. Thus, metabolic syndrome X and cardiological syndrome X are very
      close and syndrome X may be considered as a crossing between metabolic disorders
      and cardiovascular diseases.

PMID- 9555181
TI  - [Corticosteroid sensitivity, dependence and resistance in inflammatory and
      immunologic diseases. Physiopathologic review].
AB  - Patients suffering from inflammatory or dysimmunitary diseases may develop
      various clinical responses to corticotherapy. This brief article describes the
      various cellular and molecular mechanisms which underly the genetic, endocrine
      and immunitary factors involved in corticosensitivity, corticoresistance and
      corticodependence.

PMID- 9555182
TI  - [How I study syncope].
AB  - The diagnosis of the cause of a syncope is based, above all, on the basis of a
      careful clinical history obtained from the patient or from persons who attended
      one of the episodes of loss of consciousness. It should also include a careful
      clinical examination comprising an electrocardiogram and, most often, an
      echocardiogram. The selection of further investigations should be guided by the
      existence or absence of an underlying cardiac disease. In the presence of a
      patent cardiac disease, one should first try to detect a disorder of cardiac
      rhythm (Holter, mini-Holter, possibly invasive electrophysiology); a dysfunction
      of the autonomic regulation of the cardiovascular system should only be
      considered in a second step (Tilt table test). The sequence of investigation
      should be reversed when syncope occurs in a patient without underlying cardiac
      disorder.

PMID- 9555183
TI  - [Drug clinics. The drug of the month. Ranitidine bismuth citrate (Pylorid)].
AB  - Ranitidine bismuth citrate (Pylorid, Glaxo-Wellcome) is a novel salt of
      ranitidine which provides a unique combination of properties: inhibition of
      secretion of gastric acid by competitive antagonism of the action of histamine at
      the histamine H2-receptor on the gastric parietal cell, mucosal protective
      effects and anti-Helicobacter pylori action. Ranitidine bismuth citrate provides
      effective healing and symptom relief, both in duodenal ulcer disease and in
      gastric ulcer disease. When coprescribed with certain antibiotics (clarithromycin
      alone or combined with amoxicillin or nitro-imidazole), it heals ulcers,
      eradicates Helicobacter pylori and prevents recurrence of the disease. Several
      clinical studies demonstrated that ranitidine bismuth citrate is well-tolerated
      and has quite similar efficacy as proton pump inhibitors.

PMID- 9555184
TI  - [I have the hiccups].

PMID- 9555185
TI  - Restoring Class III caries using a custom matrix.

PMID- 9555186
TI  - Why direct reimbursement?

PMID- 9555187
TI  - A simplified approach to DR. Direct reimbursement.

PMID- 9555188
TI  - An introduction to ethics.

PMID- 9555189
TI  - Dr. Pinkney Adams--a dentist before his time.

PMID- 9555190
TI  - Interviewing the new dental client.

PMID- 9555191
TI  - Dental Hygiene Education in Michigan.

PMID- 9555192
TI  - Dental accreditation provides educational criteria for professional programs.

PMID- 9555193
TI  - Volunteers answer the call.

PMID- 9555194
TI  - Illinois Dental Sealant Program: 1986-1996.
AB  - Dental sealants have been shown to be an effective means of preventing pit and
      fissure caries. Despite more than 20 years of research and overwhelming evidence
      in support of the use of sealants, the dental profession has been slow to make
      use of them. This article explores the strategy used by the Illinois Dental
      Sealant Program to increase dental sealant use.

PMID- 9555195
TI  - Informed consent.

PMID- 9555196
TI  - Take the guesswork out of software purchases.

PMID- 9555197
TI  - A portrait of integrity: Arnold Bennett Donawa, DDS.

PMID- 9555198
TI  - How long do you keep your documents?

PMID- 9555199
TI  - Project Mouthguard: a survey of Illinois dentists' attitudes on mouthguards.
AB  - A random sample survey of Illinois dentists was conducted to determine their
      knowledge and experience in providing mouthguards for individuals and athletic
      teams. This article offers information on their education and involvement in
      mouthguard programs.

PMID- 9555200
TI  - Survey sez: polls reveal how dental, public relations and journalism
      professionals view each other.

PMID- 9555201
TI  - Information you need to succeed.

PMID- 9555202
TI  - Osseointegration enhanced by chemical etching of the titanium surface. A torque
      removal study in the rabbit.
AB  - Roughened implant surfaces are thought to enhance osseointegration. Torque
      removal forces have been used as a biomechanical measure of anchorage or
      osseointegration in which the greater forces required to remove implants may be
      interpreted as an increase in the strength of osseointegration. The purpose of
      this study was to compare the torque resistance to removal of screw shaped
      titanium implants having an acid etched (HC1/H2SO4) surface (Osseotite) with
      implants having a machined surface. Two custom screw shaped implants, 1 acid
      etched and the other machined, were placed into the distal femurs of 10 adult New
      Zealand White rabbits. These implants were 3.25 mm in diameter x 4.00 mm in
      length without holes, grooves or slots to resist rotation. Following a 2 month
      healing period, the implants were removed under reverse torque rotation with a
      digital torque measuring device. Two implants with the machined surface
      preparation failed to achieve osseointegration. All other implants were found to
      be anchored to bone. Resistance to torque removal was found to be 4 x greater for
      the implants with the acid etched surface as compared to the implants with the
      machined surface. The mean torque values were 20.50 +/- 6.59 N cm and 4.95 +/-
      1.61 N cm for the acid etched and machined surfaces respectively. The results of
      this study suggest that chemical etching of the titanium implant surface
      significantly increases the strength of osseointegration as determined by
      resistance to reverse torque rotation.

PMID- 9555203
TI  - Comparison of periodontal and peri-implant probing by depth-force pattern
      analysis.
AB  - The purpose of this study was to compare the tissue resistance to probing and the
      accuracy of depth determination at different force levels around implants and
      teeth. In 11 subjects 1 implant and 1 tooth at a comparable location and with
      comparable probing depth were investigated. The sites were located on either the
      mesial or distal aspect of the tooth and the implant. A probing device was used
      which allowed simultaneous monitoring of probing force and probe penetration and
      which standardized the insertion pathway for repeated measurements. The probing
      instrument was fitted with an attachment for an aiming device to take a
      radiograph with the probe tip in the sulcus, using a standardized projection
      geometry. Probing depth values were determined at 0.25, 0.50, 0.75, 1.00 and 1.25
      N probing force. The standard error of the individual measurement (Si), evaluated
      by comparison of repeated measurements in the same session, was 0.2 mm on
      implants and 0.1 mm on teeth. For implants there was a trend for slightly better
      reproducibility at higher force levels. Curve analysis of depth force patterns
      showed that a change in probing force had more impact on the depth reading in the
      peri-implant than in the periodontal situation. The mean distance between the
      probe tip and the peri-implant bone crest amounted to 0.75 +/- 0.60 mm at 0.25 N
      probing force. It is concluded that peri-implant probing depth measurements are
      more sensitive to force variation than periodontal pocket probing.

PMID- 9555204
TI  - Reproducibility of automated periodontal probing around teeth and osseointegrated
      oral implants.
AB  - Three different probing devices (Audio-Probe, Florida-Probe, Peri-Probe) were
      tested in order to determine the clinical probing depth (CPD) around clinically
      stable oral implants and their homologous teeth and to evaluate their
      reproducibility. In all 37 patients, in the age range of 24-80 years, who had
      undergone periodontal therapy and placement of 1 or more oral implants (ITI),
      were selected for the study. The CPD was determined on 75 oral implants in total
      and at 4 sites of both the implants and the control teeth at 3 visits, each 1
      week apart. At the 1st visit, the Florida-Probe and the Audio-Probe were used. At
      the 2nd visit, the Florida-Probe and the Peri-Probe and, at the 3rd visit, again,
      the Florida-Probe and the Audio-Probe were used. At each visit bleeding on
      probing (BOP) was registered. A statistically significant (P < 0.05) difference
      between the mean scores of implant and tooth sites was found showing slightly
      higher values for implant sites. A tendency for the deeper pockets to bleed more
      frequently than the shallow pockets was observed. The comparisons of differences
      of the readings of the Audio-Probe on 2 different occasions were smaller than for
      the Florida-Probe. However, comparisons between 2 different probes showed
      significantly greater measurement errors than when comparing the probes alone.
      There was a tendency for the Peri-Probe to yield the highest and the Audio-Probe
      the lowest values in inflamed sites. It was concluded that all 3 probing devices
      appeared to have adequate reproducibility both around teeth and oral implants.
      For clinical use in daily practice, the Audio-Probe was found to be the most
      simple device with the highest reproducibility.

PMID- 9555205
TI  - Titanium implants and lateral forces. An experimental study with sheep.
AB  - The purpose of this study was to investigate the resistance of titanium implants
      to horizontal forces in a sheep model. Twenty implants were inserted into the
      foreheads of 5 sheep, 4 implants on each animal. After a healing period of 3
      months, abutments were mounted on the implants. After a further healing period of
      3 weeks, the implants were loaded with a horizontal pull of orthodontic elastics.
      The force varied between 250 and 350 grams. The duration of loading was 3 months.
      After the loading period the animals were sacrificed and the forehead bones with
      implants were fixed in formalin and evaluated histologically. In the histological
      specimens no signs of infection or bone loss were found around the implants. The
      results of the present study encourage the use of titanium implants also in cases
      where constant lateral forces are present.

PMID- 9555206
TI  - A 5-year prospective clinical study of Astra Tech dental implants supporting
      fixed bridges or overdentures in the edentulous mandible.
AB  - In a 5-year prospective clinical study, 155 endosseous implants were installed in
      the mandible anterior to the mental foramina in 33 edentulous patients (13 males
      and 20 females). Usually 6 implants were installed for fixed prostheses (FP), 13
      patients with 77 implants, and 4 implants for overdentures (OD) with a Dolder
      bar, 20 patients with 78 implants. At the time of abutment connection 1 implant
      in 2 patients was found to be loose and removed. However, in both these patients
      overdentures were successfully placed on the remaining 3 implants. Narrow-beam
      radiography was used for radiological evaluation. The mean (SD) total marginal
      bone loss in 5 years was 0.48 (0.38) mm (0.36 (0.22) mm in the FP group and 0.56
      (0.45) mm in the OD group). Very few complications were reported during the 5
      years, most of them being related to the superstructures. The overall cumulative
      implant survival rate was 98.7% (100% in the FP group and 97.4% in the OD group).
      The survival rate of the superstructures was 100%. The present study has
      demonstrated that Astra Tech implants offer reliable and predictable medium-term
      support for fixed prostheses and overdentures in the edentulous mandible.

PMID- 9555207
TI  - The mini bottle brush--a new fastening device in cancellous bone.
AB  - A new design for bone implants, the bottle brush, was recently presented in a
      pilot study on marrow cavities in the femur of rabbits. In this study, the
      concept is further evaluated on a mini bottle brush. The fixture, 5 x 7 mm, with
      an implant shaft made of CP-titanium and bristles of nylon coated with sputtered
      titanium, was inserted into the cancellous bone of the medial femoral condyle in
      15 adult rabbits. The titanium fixture was compared with a similar brush without
      the titanium sputtered surface. The animals were sacrificed after 4 months and
      the quantity and quality of bone integration were evaluated with pull-out tests
      and histological examination. In both parameters, the values were significantly
      higher for the titanium-sputtered brushes, with removal forces similar to
      titanium cylinders of the same size and with a bone-to-metal contact area of
      about 50%.

PMID- 9555208
TI  - Complete nose coverage to prevent airborne contamination via nostrils is
      unnecessary.
AB  - Besides an atraumatic procedure, aseptic techniques during surgery have been
      suggested to have a positive impact on the predictability of osseointegration. To
      avoid an infection of the surgical field, coverage of the face of the patient
      (drapes) and nose (surgical mask, drape and plastic film) were advocated in order
      to reduce airborne infections and to prevent a contact contamination of
      instruments and gloves. Such a coverage, however, increases the feeling of
      claustrophobia when local anaesthesia is used and can lead to hypoxemia. The aim
      of the present study was to investigate whether the expired air via the nostrils
      could contribute to the contamination of the oral surgical field. Test blood agar
      plates were installed for 30 min under the nose of volunteers lying on a surgical
      table; once with full coverage of their nostrils, as indicated above, and once
      without. Simultaneously, control plates were installed on a table besides the
      patient to measure the basic contamination from the environment. All plates were
      incubated both aerobically and anaerobically. The number of colony forming units
      (c.f.u.) recorded on test plates after aerobic and anaerobic incubation were
      surprisingly low, with a mean score of 2.7 and 5.0 c.f.u. for the uncovered
      situation, and 2.5 and 3.3 c.f.u. for the covered situation, respectively. The
      control plates were infected by a nearly comparable number of bacteria (means
      ranging from 2.2 to 3.2). These findings indicate that covering nostrils by a
      mask and sterile adhesive plastic film is not essential in avoiding airborne
      microbial contamination. However, the use of a meshed nose guard to prevent
      contact with the highly contaminated nasal skin is highly recommended.

PMID- 9555209
TI  - Treatment of severe peri-implant bone loss using autogenous bone and a resorbable
      membrane. Case report and literature review.
AB  - Clinical case reports and animal studies have demonstrated that the principle of
      guided bone regeneration can be applied for surgical treatment of moderate to
      profound peri-implant bone loss (peri-implantitis). However, the degree of bone
      regeneration within the peri-implant osseous defect was reported to be variable
      depending on different clinical factors and on the postoperative course. Most
      papers dealing with surgical treatment of peri-implantitis advocate the use of a
      non-resorbable ePTFE membrane for secluding the peri-implant bone defect enabling
      bone regeneration. Additionally some surgeons fill the defects with allografts or
      alloplasts. The present case report demonstrates another surgical approach by
      using autogenous cancellous bone for grafting into the peri-implant bone defect
      and placing a bioresorbable polylactide membrane as a matrix barrier. The
      successful outcome of this modified surgical approach enabled the patient to
      maintain the implant for prosthetic reconstruction after early but severe bone
      loss.

PMID- 9555210
TI  - Endoscopically controlled sinus floor augmentation. A preliminary report.
AB  - Sinus augmentation has been advocated to be a surgical technique with predictable
      results in peri-implant surgery. Endoscopic surgery of the maxillary sinus so far
      has been used as diagnostic procedure. In this paper, the use of endoscopy is
      described as a low invasive adjunctive technique in sinus floor augmentation.
      After preparation of the mucoperiosteum, bone grafts can be placed under
      endoscopic control between sinus floor and mucoperiosteum. A laterobasal approach
      via a small osteotomy and a transalveolar approach are possible for mucosal
      elevation and graft placement. First clinical results are reported. Endoscopic
      sinus lift may contribute to a reduction of perioperative morbidity, reduction of
      oroantral fistulae and control of graft position. The less invasive technique may
      allow to extend the indication for sinus augmentation.

PMID- 9555211
TI  - Concepts in biocompatibility testing of dental restorative materials.
AB  - Due to the diversity of adverse biological effects which might be caused by
      dental restorative materials, biocompatibility assessment cannot rely on a single
      test but has to be based on a planned and structured approach (concept). First,
      the possible harm evoked by the material, the known data, and suitable biological
      and other test methods available must be taken into consideration. Modern
      regulatory concepts require for this purpose the services of experts to propose
      the appropriate set of required tests for a given material. The use of standards
      is generally emphasized because of better comparability of the data. Other tests
      may be chosen if more appropriate. Modern scientific concepts of biocompatibility
      testing are based on the need for rapid and cost-effective test methods, avoiding
      animal tests whenever possible. While formerly in vitro experiments did not take
      into account the special clinical situation in which the material would be used,
      modern concepts try to simulate important parameters of the in vivo situation as
      closely as possible. This may be achieved, for example, by including suitable
      barriers between the material and the target cells, by constructing appropriate
      target cells, and by choosing clinically relevant markers for measuring the
      biological effects caused by the material. There are indications so far that
      through this approach the number of animal tests can be reduced. The use of these
      methods may also lead to a better understanding of the mechanisms behind the
      biological reactions (mechanistic approach) in describing the biocompatibility of
      dental restorative materials.

PMID- 9555212
TI  - Clinical and quantitative marginal analysis of feldspathic ceramic inlays at 4
      years.
AB  - The aim of this clinical study was to evaluate feldspathic ceramic inlays both by
      clinical criteria and quantitative margin analysis in continuation of an earlier,
      identically conducted 2-year study. Fifty feldspathic ceramic inlays were
      adhesively luted in Class II preparations with all margins located in enamel. The
      inlays were evaluated clinically according to modified USPHS criteria after 3 and
      4 years. Quantitative margin analysis was performed with a scanning electron
      microscope (SEM). Clinically, the inlays showed no recurrent caries and no
      changes in colour, but superficial marginal discolouration (6%) was apparent
      after 4 years. Margins were perceptible clinically in 64% of the cases after 4
      years. Quantitative margin analysis showed significantly more marginal gaps at
      the composite/ceramic interface than at the enamel/composite interface, There was
      neither a significant decrease in perfect margins nor a significant increase in
      marginal gaps and marginal imperfections at both interfaces between the third and
      fourth year. Clinically, the inlays performed very well up to 4 years. Clinical
      evaluation using an explorer only detected substance loss in the cementation gap.
      The SEM evaluation showed significantly higher changes in marginal qualities
      during the first 2-year interval of clinical service compared to the second 2
      year interval following an exponential mathematical regularity. Quantitative
      margin analysis should be included in clinical long-term trials to detect early
      marginal deficiencies at the luting interfaces.

PMID- 9555213
TI  - The role of alveolar ridge width in dental implantology.
AB  - Sometimes, preoperative planning in dental implantology, based on sufficient
      alveolar height, cannot be verified due to transversal deficiencies. A total of
      102 bony mandibles and 95 maxillae were analysed after classification of atrophy,
      simulating implant insertion at 518 standardised edentulous cross sections with
      regard to anterior/posterior, mandible/maxilla and class of atrophy. Furthermore,
      the relation of alveolar height to possible implant length in 86 patients was
      evaluated retrospectively. Implant length reduction compared with alveolar height
      was necessary in 10% (mandibles) and 7.5% (maxillae) of the bony-jaw sections and
      52.5% (mandibles) and 41.5% (maxillae) of the patients' implant regions. In this
      respect, the class of atrophy of the bony jaws was more important than the region
      of simulation. However, the highest differences were observed between mandibles
      and maxillae, both clinically and experimentally: simulation was possible in all
      mandibles and 42.5% of the maxillae, but clinical implantation was only possible
      in 86% of 62 mandibles and 0% of 24 maxillae, mostly due to reduced alveolar
      height. Alveolar ridge width primarily affected the possible implant lengths.
      Nevertheless, in four (two mandibular and two maxillary cases) of 58 patients
      (7%) with sufficient height, a surgical procedure that had already been started
      had to be stopped. It is expected that cross-sectional radiographical techniques
      of implantation planning, including ridge-width determination, will gain
      importance in the future.

PMID- 9555214
TI  - A thin-plate spline analysis of the face and tongue in obstructive sleep apnea
      patients.
AB  - The shape characteristics of the face and tongue in obstructive sleep apnea (OSA)
      patients were investigated using thin-plate (TP) splines. A relatively new
      analytic tool, the TP spline method, provides a means of size normalization and
      image analysis. When shape is one's main concern, various sizes of a biologic
      structure may be a source of statistical noise. More seriously, the strong size
      effect could mask underlying, actual attributes of the disease. A set of size
      normalized data in the form of coordinates was generated from cephalograms of 80
      male subjects. The TP spline method envisioned the differences in the shape of
      the face and tongue between OSA patients and nonapneic subjects and those between
      the upright and supine body positions. In accordance with OSA severity, the hyoid
      bone and the submental region positioned inferiorly and the fourth vertebra
      relocated posteriorly with respect to the mandible. This caused a fanlike
      configuration of the lower part of the face and neck in the sagittal plane in
      both upright and supine body positions. TP splines revealed tongue deformations
      caused by a body position change. Overall, the new morphometric tool adopted here
      was found to be viable in the analysis of morphologic changes.

PMID- 9555216
TI  - Erosion on abraded dental hard tissues by acid lozenges: an in situ study.
AB  - The aim of this study was to analyse the erosive effect of acidic lozenges and to
      compare it with that of orange juice, known to have the capacity to cause
      erosion. Two acidic, sugar-free lozenges and orange juice were tested in situ in
      nine patients. Changes in surface Knoop microhardness and change in the surface
      texture were assessed. The results revealed that orange juice and one acidic
      lozenge were--under the conditions of this experiment--capable of significantly
      softening abraded enamel (P < or = 0.017). It was concluded that excessive
      consumption of acidic lozenges could have the potential to enhance existing
      dental erosion.

PMID- 9555215
TI  - Marginal adaptation to enamel of a polyacid-modified resin composite (compomer)
      and a resin-modified glass ionomer cement in vivo.
AB  - Recently, new restoratives, such as resin-modified glass ionomer cements (RMGIC)
      and polyacid-modified resin composites (PMC) were introduced for class III and
      class V cavities. Both materials use simplified cavity conditioning methods. The
      well-established treatment of enamel with phosphoric acid has been replaced with
      treatment using weaker acids. The purpose of this study was to investigate in
      vivo the quality and durability of the marginal bond to enamel of these
      restorative system and compare it with a resin composite restorative, Seventeen
      patients received class III restorations of each of the three restoratives. At
      baseline and after 1 year replica impressions were made for investigation of the
      vestibular margins with the scanning electron microscope. Semi-quantitative
      analysis of the enamel-restorative interfaces was performed at x200 and x1000
      magnifications. The three restorative systems showed good marginal adaptation and
      high percentages of the length of the margins investigated at baseline were gap
      free (82%-92%). The resin composite showed significantly better adaptation than
      the other materials. The marginal quality decreased significantly after 1 year
      for the resin composite and the polyacid-modified resin composite. The RMGIC
      showed improved sealing after 1 year in vivo, probably due to continuing water
      uptake. The percentages of gap-free margins of the total marginal length observed
      at 1 year were 73%, 90%, and 84%, respectively, for the PMC, the RMGIC and the
      resin composite. The difference between the PMC and the RMGIC was significant. In
      conclusion, a good marginal quality was seen for all three restorative systems in
      class III cavities after a period of 1 year.

PMID- 9555217
TI  - Comparing dental utilization of United States of America military recruits with
      their employed civilian cohorts.
AB  - This study compares the dental utilization of United States of America (USA)
      military recruits with that of their employed civilian cohorts. Military data
      were collected between February and June 1994 at one recruit in processing site
      per service, using self-administered questionnaires on a prestratified,
      systematic, random sample of 2369 Army, Air Force, Navy, and Marine recruits.
      Women and blacks were oversampled. Civilian data come from the most recent oral
      health survey of working adults in the USA. Results show that annual dental
      utilization rates of military recruits equal or are less than those of their
      employed civilian cohorts. Overall, 38% of recruits have seen a dentist in the
      past year, while 30% have not seen a dentist in 3 or more years. Such low
      consumption of dental care suggests that dental utilization habits prior to
      service entry do not contribute appreciably to the high dental utilization rates
      seen among active duty US military personnel.

PMID- 9555218
TI  - Clinical evaluation of Helioseal F fissure sealant.
AB  - Unfilled resins are commonly in use as sealant material. In addition, there are
      filled sealants available. Helioseal F is a newly developed filled material with
      fluoride release. In this clinical trial, Helioseal F has been evaluated in one
      lower molar versus Delton opaque as an unfilled control in lower molars. After 12
      months there were no significant differences in retention, porosities, and the
      number of clinically unacceptable margins between the materials. The complete
      retention was 30 out of 31 examined teeth for Delton and 28 out of 31 for
      Helioseal F. After 1 year of clinical testing, these results indicate that a
      sealant containing fluoride-releasing particles did not show a significant
      difference in retention rate compared to an unfilled conventional sealant.
      However, long-term results concerning marginal adaptation should be evaluated.

PMID- 9555219
TI  - Who we are. Highlights of the 1997 ADAA Demographics Survey.

PMID- 9555220
TI  - Current prosthodontic perspectives of implant dentistry: focusing on age
      guidelines.

PMID- 9555221
TI  - Team approach to implant dentistry: how should it work? (Part II)

PMID- 9555222
TI  - Bone expansion techniques reduce need for grafting.

PMID- 9555223
TI  - Dual templates for effective placement of root-form implants.

PMID- 9555224
TI  - Current implantology affects traditional perio-prosthetics.

PMID- 9555225
TI  - Ascending ramus offered as alternate harvest site for onlay bone grafting.

PMID- 9555226
TI  - Calcium sulfate: a valuable addition to the implant/bone regeneration complex.

PMID- 9555227
TI  - Preferred designs for mandibular implant overdentures.

PMID- 9555228
TI  - Reduce bone loss, enhance outcomes with immediate implant placement.

PMID- 9555229
TI  - Safeguards and precautions for risk management in implant dentistry.

PMID- 9555230
TI  - The key to peri-implant esthetics: hard- and soft-tissue management.

PMID- 9555231
TI  - Occlusal fulfillment for today's implant restorative/prosthetic dentist.

PMID- 9555232
TI  - Nasal sinus lift: an innovative technique for implant insertions.

PMID- 9555233
TI  - How to insert the mixed tooth/implant arch fixed prosthesis using cement and
      screw fixation.

PMID- 9555234
TI  - Perfection in emergence profiles: a road map for ideal placement of the single
      tooth implant.

PMID- 9555235
TI  - The regional acceleratory phenomenon: an up-to-date rationale for bone
      decortication.

PMID- 9555236
TI  - How to achieve anterior symmetry in implant prosthodontics with single-tooth
      replacements.

PMID- 9555237
TI  - Sinus lift complications: avoiding problems and finding solutions.

PMID- 9555238
TI  - Proper restoration-generated site development leads to exemplary implantations.

PMID- 9555239
TI  - How to combine cementation and retrievability of implant prostheses: why access
      should be attainable.

PMID- 9555240
TI  - Harvesting autogenous cancellous bone from the cranium for oral placement of
      implants.

PMID- 9555241
TI  - A regeneration update: resorbable and non-resorbable membranes.

PMID- 9555242
TI  - Double guidance approach for the improvement of the single-tooth implant
      replacement.

PMID- 9555243
TI  - High-tech case presentations in implant dentistry foster value-based decisions.

PMID- 9555244
TI  - Sinus lift revisited: an update on current implant-related procedures.

PMID- 9555245
TI  - Harvesting autogenous cancellous bone from the tibia for enhanced oral implant
      placements.

PMID- 9555247
TI  - Flap designs and suturing techniques related to anterior single-tooth implant
      placement.

PMID- 9555246
TI  - Current usage of bone fill as an adjunct in implant dentistry.

PMID- 9555248
TI  - Loss of vertical dimension, tooth loss, and migration: treatment planning for
      implant prosthodontics.

PMID- 9555249
TI  - An innovation in implant template design allows more accuracy during placement.

PMID- 9555250
TI  - Characterization of 50wt%SiO2-20wt%P2O5-30wt%CaO glass-ceramic powders prepared
      by the sol-gel process.
AB  - Glass-ceramic powders with the oxide batch formulation 50wt%SiO2, 20wt%P2O5 and
      30wt%CaO were prepared by the sol-gel process using tetraethoxysilane, calcium
      nitrate and phosphoric acid as raw materials. The obtained gels and powders were
      characterized by TG-DTA thermal analysis, FTIR analyses and XRD measurements. The
      results indicated that (1) heating to more than 600 degrees C brought about
      elimination of -OC2H5 side chains from gels, and formation of a SiO2-based glass
      network, (2) crystallization such as Ca3(PO4)2 notably occurred in the SiO2-based
      glass matrix when heated to more than 900 degrees C, (3) -OH groups existed on
      SiO2-based glass-ceramic surfaces in the temperature region less than 900 degrees
      C, and (4) the melting point of this composition was more than 1400 degrees C.
      This study suggests that sol-gel-derived SiO2-based glass-ceramic powder
      containing P and Ca might be useful as bioactive implant materials.

PMID- 9555251
TI  - Glass transition temperatures of dental porcelains determined by DSC measurement.
AB  - The differential scanning calorimetry (DSC) curves for three commercial dentin
      and incisal porcelains fused-to metal were measured using high-temperature DSC.
      The glass transition temperatures (Tg) were determined from the DSC curves at
      heating rates of 7-20 degrees C/min, and the activation energy was derived from
      an Arrhenius plot of negative reciprocal Tg vs. logarithm of heating rate. The Tg
      of the dental porcelains depended on the content of aluminum oxide, whereas the
      activation energy depended on the content of sodium oxide. The ultra-low fusing
      type porcelains had a low activation energy due to the higher content of sodium
      oxide than the other porcelains.

PMID- 9555252
TI  - Influence of modification of Na2O in a glass matrix on the strength of leucite
      containing porcelains.
AB  - The desirable thermal properties of matrix glass to the strength of feldspar
      porcelain with leucite crystal were investigated. Five kinds of feldspar glasses,
      each with different a content of Na2O, were prepared for the matrix glasses of
      the leucite-containing porcelains. The specimens were arranged by mixing each
      glass powder with high-purity natural leucite crystals (0, 20 and 40%) followed
      by firing. The thermal properties of the glass and the transformation temperature
      of the leucite were measured. A three-point bending test was performed to measure
      the flexural strength of the porcelains. The glass transition temperature and
      deformation temperature of the glass-only porcelains were decreased as the Na2O
      content increased. The Na2O-modified glasses were substantially strengthened by
      the leucite dispersion. However, the strength of the porcelains was affected by
      the relation between the transformation temperature of the leucite and the
      thermal properties of the glass matrix. It was concluded that control of the
      residual stress in the composite porcelain is an important factor in developing
      high strength porcelain containing leucite.

PMID- 9555253
TI  - A coherent phase diagram of the [(AuCu)0.86Ag0.14]1-XPtX pseudobinary section in
      Au-Cu-Ag-Pt quaternary system.
AB  - In order to determine a coherent phase diagram of the [(AuCu)0.86Ag0.14]1-XPtX
      pseudobinary system, phase identifications and analyses of the microstructural
      configurations were performed by means of transmission electron microscopy.
      Various phase regions were detected in the coherent phase diagram as follows; (1)
      alpha 0 (fcc) single phase region, (2) two-phase region (alpha 1 + alpha 2), (3)
      AuCu I (L10) + alpha 0, (4) AuCu I + alpha 2, (5) AuCu II (L10-S) + alpha 2, (6)
      AuCu I + AuCu II + alpha 2, (7) AuCu I single phase region. Microstructural
      features of these regions relating to the phase transformations were described.

PMID- 9555254
TI  - Effects of aging on tensile fatigue strength of bovine dentin.
AB  - The effects of aging on the tensile fatigue strength of bovine dentin were
      investigated. Tensile tests and tensile fatigue tests were performed in 37
      degrees C water with bovine dentin specimens of two different age groups. The
      tensile strengths of the young group and the adult group were 74.0 MPa and 72.7
      MPa, respectively; there was no significant difference between the young and the
      adult group. However, the tensile fatigue strength of the adult group, 46.9 MPa,
      was significantly weaker than that of the young group, 51.0 MPa. There was a
      obvious difference between the tensile fracture surface and the tensile fatigue
      fracture surface; a smooth surface of the peritubular dentin and an uneven
      surface of the intertubular dentin were clearly distinct in the fatigue fracture
      surface. Plugged dentinal tubules and narrower dentin tubules were commonly
      observed in the adult group. These morphological changes were suggested to be the
      reason for the decrease in the tensile fatigue strength with aging.

PMID- 9555255
TI  - Erosion process of light-cured and conventional glass ionomer cements in citrate
      buffer solution.
AB  - The aim of this study was to clarify the erosion behavior of light-cured glass
      ionomer cement. One light-cured glass ionomer cement and two conventional
      chemically-cured glass ionomer cements were immersed in citric acid buffer
      solutions of pH 4 and pH 6. Fluoride release was almost the same in both types of
      cements, irrespective of pH. The amounts of other species eluted, such as Al, Sr,
      Si and P2O5 were smaller in the light-cured glass ionomer cement than in the
      conventional ones at pH 4. The amounts of species eluted at pH 6 were almost the
      same in both types of cement. Dissolution of the light-cured cement in pH 4
      solution was controlled by the diffusion of the eluted species in the cement
      matrix. On the other hand, dissolution of the conventional cements was controlled
      by both diffusion and surface reaction. The surface features of the cements after
      erosion corresponded well to the dissolution mechanism. In pH 6 solution,
      dissolution of the cements was mainly controlled by diffusion of the species in
      the cement.

PMID- 9555256
TI  - Development of the computerized dental cast form analyzing system--three
      dimensional diagnosis of dental arch form and the investigation of measuring
      condition.
AB  - To analyze the functional and morphological harmonies of the tooth and dental
      arch, a computerized system to measure a dental cast and to detect the apex of
      dental cusps and angle points of incisors was developed. Detailed morphology in
      the measured dental cast could be displayed distinctively by computer graphics
      (CG) with a surface model. Accuracy in determining the position of the apex of
      the dental cusp was examined by increasing the measuring pitch from 50 microns to
      400 microns, the error increased gradually with increased measuring pitch. Taking
      the measuring error, the time for measurement and the memory size for analysis
      into account, a measuring pitch of 200 microns was determined to be reasonable.
      Three-dimensional data measurements from the apex of the dental cusp in molar,
      and the mesial and distal angles in canine and incisor were fitted to a
      polynomial formula. In the present measured model, the 4th order polynomial
      formula was used for the dental arch, and the 2nd order polynomial formula was
      used for the anteroposterior and lateral occlusal curves. These formulae could be
      simultaneously superimposed on the surface model of the dental cast, and
      displayed using CG.

PMID- 9555257
TI  - Effect of Pd and In on mercury evaporation from amalgams.
AB  - The amount of Hg vapor released from "synthesized" gamma 1 with 1% (wt) Pd was
      reported to be less than 30% of that from gamma 1 with no Pd. This study tested
      the hypothesis that Hg evaporation from Pd-containing amalgams decreases with Pd
      concentration and that In also reduces Hg vapor. Specimens (4 mm dia, 8 mm long)
      were prepared by triturating Ag-Sn(25%)-Cu(12%) alloy powder containing 0.5-9.0%
      Pd with pure Hg and by triturating 3% Pd alloy powder with Hg containing 1-5% In
      (all residual Hg approximately equal to 62%). The total amount (ng/mm2) of Hg
      vapor released at 37 degrees C from freshly prepared amalgams was measured. Pd (3
      9%) in the powder significantly (p < 0.05) decreased Hg vapor release from
      amalgams during setting. Use of In-containing Hg also reduced Hg vapor release
      (5% In, p < 0.05). The reduction in the Hg vapor pressure by adding Pd and the
      rapid oxide film formation on the In-containing amalgam appear to work together
      to reduce Hg vaporization from these amalgams.

PMID- 9555258
TI  - Behavior of pure gallium in water and various saline solutions.
AB  - This study investigated the chemical stability of pure gallium in water and
      saline solutions in order to obtain fundamental knowledge about the corrosion
      mechanism of gallium-based alloys. A pure gallium plate (99.999%) was suspended
      in 50 mL of deionized water, 0.01%, 0.1% or 1% NaCl solution at 24 +/- 2 degrees
      C for 1, 7, or 28 days. The amounts of gallium released into the solutions were
      determined by atomic absorption spectrophotometry. The surfaces of the specimens
      were examined after immersion by x-ray diffractometry (XRD) and x-ray
      photoelectron spectroscopy (XPS). In the solutions containing 0.1% or more NaCl,
      the release of gallium ions into the solution was lowered when compared to
      deionized water after 28-day immersion. Gallium oxide monohydroxide was found by
      XRD on the specimens immersed in deionized water after 28-day immersion. XPS
      indicated the formation of gallium oxide/hydroxide on the specimens immersed in
      water or 0.01% NaCl solution. The chemical stability of pure solid gallium was
      strongly affected by the presence of Cl- ions in the aqueous solution.

PMID- 9555259
TI  - Want to go with the flow? A state-side ride with the tide might spell disaster
      for your Canadian practice.

PMID- 9555260
TI  - Building a successful dental partnership.

PMID- 9555261
TI  - Getting rich from scratch: a twelve point checklist.

PMID- 9555262
TI  - What do you really want from your practice?

PMID- 9555263
TI  - Enhance scheduling: give the patient a reason to come back.

PMID- 9555264
TI  - From mediocrity to mastery: a practice case study.

PMID- 9555265
TI  - Sound advice to build success.

PMID- 9555266
TI  - How to make your hygiene department more profitable.

PMID- 9555267
TI  - From concept to reality ... it's leading edge dentistry.

PMID- 9555268
TI  - Building partnerships with your dental suppliers & laboratories.

PMID- 9555269
TI  - Get your lab fit for profits. Experience the benefit$ of bringing back their
      smiles.

PMID- 9555270
TI  - Not just another pretty place.

PMID- 9555271
TI  - Laboratory lotto? Are you gambling with your success?

PMID- 9555272
TI  - The benefits of using an employment contract.

PMID- 9555273
TI  - Choosing the right partner for your practice.

PMID- 9555274
TI  - Ethics, anyone? Ethics, everyone!

PMID- 9555276
TI  - Legislative change--discussions are heating up.

PMID- 9555277
TI  - Responsibility and the practice environment.

PMID- 9555278
TI  - Off-label prescribing for infants.

PMID- 9555279
TI  - For your patients: when your child has an ear infection.

PMID- 9555280
TI  - Asthma in adolescents.

PMID- 9555281
TI  - A flexible option for adolescents with diabetes. Insulin pump therapy.

PMID- 9555282
TI  - Protecting young athletes. Achieving injury prevention and health maintenance.

PMID- 9555283
TI  - Attention-deficit hyperactivity disorder. The psychostimulants and beyond.

PMID- 9555284
TI  - Respiratory syncytial virus. Understanding this pediatric threat.

PMID- 9555285
TI  - Otitis media with effusion. Outlining strategies and controversies.

PMID- 9555286
TI  - Environmental tobacco smoke.

PMID- 9555287
TI  - The challenge of chickenpox. Vaccine is best bet against this childhood illness.

PMID- 9555288
TI  - Responding to pediatric pain. A new way of thinking.

PMID- 9555289
TI  - What we give to, and receive from, our patients.

PMID- 9555291
TI  - Carol Bradley, MSN, RN, president-elect for AONE.

PMID- 9555290
TI  - Managing ICU bed changes to match patient acuity.

PMID- 9555292
TI  - Implementing best practices.

PMID- 9555293
TI  - Ten steps to a patient-driven interdisciplinary care plan.

PMID- 9555294
TI  - Spirituality in the health care workplace.

PMID- 9555295
TI  - Building a values-driven, visionary organization.

PMID- 9555296
TI  - Transforming knowledge to a healing environment.

PMID- 9555297
TI  - We've all been there...

PMID- 9555298
TI  - Are we doing enough to protect our children on the roads?

PMID- 9555299
TI  - The principles of mixing and handling to minimise potential hazards of methyl
      methacrylate bone cement.

PMID- 9555301
TI  - The Protection From Harassment Act.

PMID- 9555300
TI  - Teamwork in the operating department.
AB  - The Gynaecology theatre team of the Leicester Royal Infirmary NHS Trust were
      runners-up in the 1997 3M/NATN joint award. This article is a report of their
      work on the concept of teamwork and its benefits to the organisation and delivery
      of patient care in the operating department.

PMID- 9555302
TI  - Workplace bullying--the abuse of power.

PMID- 9555303
TI  - Shared governance--a personal view.

PMID- 9555304
TI  - Education in the workplace.
AB  - Other parts of the portfolio included sections for their six monthly appraisals,
      reports on objectives and other projects. At this point fifteen D grade nurses
      have subscribed to the PDP and an average of two per month are being added to it.
      It is hoped that the PDP will lead to the increased motivation of all staff and
      increased promotion prospects for the D grade nurses and thus have an impact on
      the recruitment and retention of staff.

PMID- 9555305
TI  - 'Green door, what's that secret you're keeping'!

PMID- 9555306
TI  - Adding degrees C to old shouldn't read cold.

PMID- 9555307
TI  - Surfing the "Net".

PMID- 9555310
TI  - [Systemic nursing intervention in couples in which one member has cardiac
      insufficiency].
AB  - Chronic heart failure is a family affair since the spouse's quality of life is
      affected as much as that of the patient. This article deals with three clinical
      cases exploring the couple's perceptions of how the illness affected their
      marital relationship and how helpful the family systems nursing interventions
      have been. Three themes emerged from the analysis of the relationship between the
      evolution of the illness and the marital dynamics, and these are: a search for a
      balance between protectiveness/overprotectiveness, a reassessment of the marital
      relationship, and the adoption of new coping strategies. The family systems
      nursing interventions that were perceived as the most helpful were the systemic
      questionf1p4++ and the exploration of the couple's strengths and resources. These
      interventions allowed the couple to: 1) share their illness experience; 2)
      increase their understanding of the relationship between the illness and their
      marital dynamics, and 3) reflect on different ways to enhance their competence
      and resources in meeting with the challenges of this type of cardiac health
      problem.

PMID- 9555308
TI  - [Is the family important in cardiovascular care?].
AB  - Family care is an increasingly important component of nursing practice. A
      systemic perspective on a cardiac health problem compels nurses to consider the
      reciprocal relationship between the evolution of the illness and the patient's
      family dynamics. An increasing number of studies focus on how an illness impacts
      on the family and how the family can be either a source of stress for the patient
      or a welcome support. Based on various studies and on clinical examples from the
      authors' practice, this article stresses the importance for nurses to include the
      family in their cardiovascular nursing care whatever the clinical context or
      their expertise in family nursing. Systemic questioning that facilitates the
      sharing of the illness experience between family members and the exploration of
      the family's strengths and resources are nursing interventions that can be
      practiced in all clinical contexts. These interventions are important because
      they can considerably alleviate the patient's as well as and the family's
      suffering.

PMID- 9555311
TI  - Family partnership in care: integrating families into the coronary intensive care
      unit.
AB  - Since the introduction of Family Partnership in Care in the CICU and other pilot
      units, many changes have been made. Education sessions are now unit specific
      rather than in groups with multiple units. This facilitates the discussion of
      unit-specific educational and implementation needs. In addition, unit-specific
      sessions allow for some case scenario/role playing activities to facilitate
      learning and application of the FPCP elements to the unique culture of the unit.
      Finally, less emphasis is placed on the documentation, while greater emphasis is
      placed on the philosophy behind the program and the nurses values and attitudes
      towards families. Overall, the implementation of the FPCP in CICU has had a
      positive impact on staff and patients. Staff awareness regarding the importance
      of involving family in the patient's care and the benefits of this has been
      heightened. Staff who were initially very skeptical have become strong advocates
      for the program. The successful shift with families in "doing for" to "working
      with" has enhanced the professional practice of many nursing staff and
      contributed to the overall unit functioning. Finally, the feedback from patients
      and their care partners and the independence and informed decision-making
      fostered by designing a plan of care with staff validates the importance of this
      program in a critical care area.

PMID- 9555313
TI  - From loss to action.

PMID- 9555314
TI  - Seeking to prevent further tragedy.

PMID- 9555315
TI  - Pharmaceuticals and osteoporosis.

PMID- 9555316
TI  - Cancelling immunization program a bad idea.

PMID- 9555317
TI  - Article on physical punishment biased.

PMID- 9555318
TI  - Hamelin responds to feedback.

PMID- 9555319
TI  - The future supply of registered nurses in Canada.

PMID- 9555321
TI  - How men learn about health.

PMID- 9555320
TI  - Patterns of renewal in mothers who are nurses.

PMID- 9555322
TI  - [Urinary function integrity in the elderly person].
AB  - How can nurses help preserve the integrity of elimination in the elderly?
      Further, what new perspectives must they bring to practice? First, health
      professionals must rid themselves of their misconceptions, especially the belief
      that incontinence is "normal" in the aging process. The authors provide avenues
      for reflection and action, with a view to arriving at a dynamic clinical practice
      focusing on quality of life and the well-being of the individual. In terms of new
      perspectives, nurses are encouraged to stop limiting themselves to assisting with
      personal hygiene because this deprives the client of possible recourse to a
      better adaptation. Nurses must no longer dispense comfort by reassuring the
      incontinent person that "there's no harm done". This message ignores the real
      life experience associated with the problem and reinforces the idea of normality.
      Assessment of the client's condition must go beyond the superficial and instead
      target interventions that lead to a resolution. Updating the caregiver's and the
      client's knowledge, enhancing the nurse's role in prevention and treatment,
      combining various approaches to care and improving communication are good places
      to start.

PMID- 9555323
TI  - Home phototherapy for uncomplicated neonatal jaundice.

PMID- 9555324
TI  - The ten worst and best days of my career.

PMID- 9555325
TI  - Who decides what's in the public interest?

PMID- 9555326
TI  - Your role in giving weight-control advice.

PMID- 9555327
TI  - Depot injections at home or clinic? Letting clients choose.

PMID- 9555328
TI  - Exercising for better health and mobility.

PMID- 9555330
TI  - Treating eczema in ethnic minority groups.

PMID- 9555329
TI  - Dilemmas in moving and handling patients.

PMID- 9555331
TI  - The role of the papillomavirus in cervical changes.

PMID- 9555332
TI  - The menopause without HRT.

PMID- 9555333
TI  - Role of immunisation in the care of the chronically sick.

PMID- 9555334
TI  - Using alginate dressings: a cost-effective option.

PMID- 9555335
TI  - Pressure relief seating: are your patients comfortable?

PMID- 9555337
TI  - Putting food scares into perspective.

PMID- 9555336
TI  - Night nurses provide vital service.

PMID- 9555338
TI  - The role of skin-prick testing in asthma care.

PMID- 9555339
TI  - Role of diet in the management of diabetes.

PMID- 9555341
TI  - Can HRT help in Alzheimer's disease?

PMID- 9555340
TI  - Treating rashes in the groin.

PMID- 9555342
TI  - A tale of the unexpected.

PMID- 9555343
TI  - Management of constipation in children.

PMID- 9555344
TI  - Accountability in prescribing.

PMID- 9555345
TI  - Management of paediatric pain 1: Non-drug approaches.

PMID- 9555346
TI  - Management of paediatric pain 2: Drug therapies.

PMID- 9555347
TI  - A multidisciplinary approach to foot care in diabetes.

PMID- 9555348
TI  - Choosing antiseptic dressings for infected wounds.

PMID- 9555349
TI  - Effective communication in continuity of stoma care.

PMID- 9555350
TI  - Reflections on scholarship in diabetes education.

PMID- 9555351
TI  - Education--a lifelong process.

PMID- 9555352
TI  - Mini-residency on diabetes care for healthcare providers: enhanced knowledge and
      attitudes with unexpected challenges to assessing behavior change.

PMID- 9555353
TI  - "Learn, taste, and share": a diabetes nutrition education program developed,
      marketed, and presented by the community.

PMID- 9555354
TI  - Participation in a diabetes education and care program: experience from the
      diabetes care for older adults project.
AB  - There is very little reported information concerning the participation of older
      adults in diabetes education and care programs, factors related to their
      attendance, and the influence of attendance on program outcomes. In this study,
      which was part of a larger study of insulin therapy, subjects (> or = 65 years
      old) assigned to the intensive management group (n = 53) were provided with
      educational sessions during the 18-month study period. Data for this group were
      examined to determine factors that influenced enrollment and attendance.
      Attendance rates for individual participants averaged 72% during the first 6
      months and 68% during the subsequent 12 months. Demographic factors, baseline
      knowledge test scores, and baseline glycosylated hemoglobin levels did not
      significantly influence participation. Greater distance from the clinic and
      shorter time using insulin were significantly related (P = .05) to attendance.
      Perceived benefits of the program included diabetes education (45%), glucose
      control (23%), and interacting with others who have diabetes (23%).

PMID- 9555355
TI  - Greatest fears of type 1 and type 2 patients about having diabetes: implications
      for diabetes educators.
AB  - This exploratory study was undertaken to describe the differences in the greatest
      fears about having diabetes between type 1 and type 2 patients. Frequency
      distributions, measures of central tendency, and nonparametric statistics were
      employed to examine the traits of the sample and to make comparisons between type
      1 and type 2 patients. Content analysis was used to describe and analyze the
      subjects' responses to the question, What is your greatest fear about having
      diabetes? Subjects' answers to this question were categorized and scored as
      representing fear of either a long-term or acute complication based on the
      clinical judgment of the authors. Results revealed that both type 1 and type 2
      patients were likely to have given responses that were suggestive of fear of long
      term complications. The major fears concerned amputation, cardiovascular disease,
      nephropathy, neuropathy, retinopathy, and stroke. The findings of the present
      investigation suggest that diabetes educators may need to address patients' fears
      of long-term complications directly and effectively. Several areas of research
      that grew out of this exploratory study were recommended for future
      consideration.

PMID- 9555356
TI  - Feasibility and use of an Internet support service for diabetes self-management.
AB  - Diabetes self-management is a challenging task due to its complexity and ever
      present barriers to self-care. A key issue for patients, providers, and
      healthcare systems is how to deliver personalized behavioral support in ways that
      are affordable and can reach most patients. The Internet offers several
      advantages in this regard because it is available 24 hours a day, low cost, and
      capable of reaching thousands of patients. Although Internet sites for diabetes
      support are popular, they have not been evaluated. For this study, a Web site for
      diabetes self-management that emphasized personalized goal setting, feedback, and
      social support was developed. Over a 10-week period, 111 different persons logged
      onto D-NET for a total of 21,046 accesses. Users included persons across a broad
      age range (up to age 77 years) and duration of diabetes. The most popular areas
      of the site were the Social Support Conference and the Diabetes Information
      Pages. User ratings revealed high satisfaction with the service. The Internet has
      great potential for providing needed support and services for patients with
      diabetes and other chronic illnesses.

PMID- 9555357
TI  - A primary intervention program (pilot study) for Mexican American children at
      risk for type 2 diabetes.
AB  - Many chronic diseases that are leading causes of morbidity and mortality can be
      prevented or controlled by primary or secondary interventions. Type 2 diabetes
      with its complications constitutes a major health problem, especially among
      Mexican Americans. The purpose of this pilot study was to develop an age- and
      culturally appropriate primary intervention program for Mexican American children
      at risk of type 2 diabetes. The sample included 37 Mexican American children ages
      7 to 12 years who had at least one parent or grandparent with type 2 diabetes. A
      health screen of physiologic risk factors, a nutritional assessment, and a
      diabetes knowledge test were administered before and after the program. The eight
      session activity oriented educational program focused on nutrition, exercise, and
      diabetes knowledge. Due to small sample size and limited study time, changes in
      physiologic factors and diet were not analyzed for statistical significance.
      Analysis of individual factors showed a trend toward more normal values. Results
      of this pilot program indicated that health intervention projects may be
      effective in helping children at risk of type 2 diabetes adopt healthier
      lifestyles.

PMID- 9555359
TI  - Natural products and diabetes treatment.
AB  - Many natural products are promoted to improve the health status of patients with
      diabetes by people making a profit on these products. Few of these claims have
      any scientific basis. Certain natural products are potentially damaging to
      patients with chronic diseases, especially if the products are used instead of
      proven scientific treatment regimens. Many individuals believe that if a product
      is natural it must be effective and safe. What is ironic is that if the products
      were safe and effective, and if studies would have been done on humans to prove
      safety and effectiveness, the sales of the products would greatly increase (as
      opposed to present limited sales as herbs from health food stores). Some of the
      products do have a beneficial effect, especially as a placebo if the patient
      believes that the product is going to work. As can be seen from the summary of
      products that are listed here that claim to improve the treatment of patients
      with diabetes, very few are available in a standard form that would produce a
      known positive effect. The few products that do have a mild impact on lowering
      blood glucose levels are much less effective than standard treatments. In a
      recent review of the role of plant-derived drugs and herbal medicines in
      healthcare, no natural products were listed as having a beneficial effect on
      diabetes. Diabetes care providers need to confront the issue of the use of
      natural products with their patients. Patients should be taught the importance of
      using proven, effective treatment regimens. Any patient who decides to use a
      natural product should be followed closely to make sure that no toxic effects
      occur and that treatment objectives are achieved.

PMID- 9555358
TI  - Focus on insulin resistance in type 2 diabetes: therapeutic implications.
AB  - Type 2 diabetes is extremely common and increasing in the United States. The
      pathophysiology of type 2 diabetes is a combination of increased insulin
      resistance and inadequate secretion. The main risk factors for diabetes are
      family history, obesity, sedentary lifestyle, ethnic background, age, and a
      history of gestational diabetes. Diet and exercise, the cornerstones of diabetes
      management, will improve insulin sensitivity and indirectly augment insulin
      secretion. Until recently, the only pharmacological approaches to diabetes were
      sulfonylureas and insulin, which either augment insulin secretion or replace
      insulin, thus acting only on the insulin side of the equation. Recently, a series
      of new drugs have become available that are capable of decreasing hepatic glucose
      output (metformin), slowing postprandial glucose absorption (acarbose), and
      improving peripheral insulin sensitivity (troglitazone). With these drugs, either
      alone or in combination, and behavioral therapies, it is now feasible to achieve
      good to outstanding glycemic control in most individuals with type 2 diabetes.

PMID- 9555360
TI  - Esophageal varices: treatment and implications.
AB  - The purpose of this article is to present an overview of esophageal varices. The
      causes of esophageal varices and the current treatments are examined. Information
      is provided regarding surgical and nonsurgical forms of treatment. Various
      aspects of nursing care are discussed, including the implications involved in the
      emergency setting, psychological needs, and education for patients and their
      families.

PMID- 9555361
TI  - The hidden illness of endoscopy patients: mental health disorders, Part III.

PMID- 9555362
TI  - Understanding pediatric intestinal pseudo-obstruction: implications for nurses.
AB  - Pseudo-obstruction is actually a group of disorders resulting in bowel
      dysmotility in the absence of anatomic obstruction. Because of varied pathologic
      abnormalities of the GI tract involved in the disorder, pseudo-obstruction has
      been reported in the literature under different names, including
      hypoganglionosis, chronic adynamic ileus, pseudo-Hirschprung's disease, visceral
      neuropathy, visceral myopathy, and megacystis-microcolon-intestinal
      hypoperistalsis syndrome. Although a rare condition, its effects are severe,
      disabling, and life-threatening in pediatric clients. Prognosis is inversely
      correlated with age and is especially poor in those children with symptoms as
      newborns. Management involves promoting nutrition adequate for growth, treating
      symptoms, and preventing complications. Total parenteral nutrition is almost
      always required, and its long-term use is associated with chronic cholestasis and
      potential hepatic failure. Nurses may encounter pediatric clients with this
      disorder and their families in many different healthcare arenas, such as in
      radiology departments, ambulatory care, and acute and home care settings. The
      purpose of this article is to review current literature on this disease and
      summarize information useful to nurses.

PMID- 9555363
TI  - The nurse endoscopist: reality or fiction?
AB  - In this article, the author describes a study conducted to determine whether
      advanced practice registered nurses (APRNs) should perform endoscopic procedures,
      such as colonoscopy and esophagogastroduodenoscopy. Questionnaires were mailed to
      APRNs belonging to the Society of Gastroenterology Nurses and Associates.
      Questionnaire items pertained to demographics, current activities, interest in
      performing GI endoscopic procedures, and barriers to performing GI endoscopic
      procedures. Over 70% of respondents approved of nurses performing diagnostic
      endoscopic procedures, yet 80.6% did not think that nurses should perform
      therapeutic endoscopic procedures. Training opportunities were limited. The
      barriers to performing endoscopic procedures included liability, third-party
      reimbursement, lack of physician support, lack of policies, and lack of
      education. APRNs should develop policies and establish acceptable training
      guidelines and competency rates in performing GI endoscopic procedures.

PMID- 9555364
TI  - Medication history and Helicobacter pylori testing.

PMID- 9555365
TI  - Camp Magic: a GI camp.

PMID- 9555366
TI  - Infergen (interferon alfacon-1).

PMID- 9555367
TI  - The more things change, the more they stay the same: whither midwifery?
AB  - The pace of change is said to increase over the next few years. One of the most
      significant recent changes has been the "McDonaldization of Society". The notion
      of "fastness" is permeating all society, including health and education. The
      concentration of rationalization through the principles of efficiency,
      calculability predictability and control, when extended to its logical
      conclusion, results in irrationality or dehumanization. Childbirth has been
      "McDonaldized" by the medical profession, but modern midwifery, is leading the
      way in an anti McDonald's movement to rehumanize it. Returning to past values
      contained in aesthetics, use of the partnership model, different forms of
      research and political action, midwifery is taking control of childbirth away
      from the rationalists and returning it to women. It is reclaiming childbirth by
      placing value on women and empowering them to take control of their own
      childbirth.

PMID- 9555368
TI  - Women have innate knowledge and wisdom to birth.

PMID- 9555369
TI  - Re: Women have the innate knowledge and wisdom to birth.

PMID- 9555371
TI  - Re: Letter to the editor, Dr Nick Silberstein ACMI Journal Sept 1997, Vol 10, No.
      3, p5.

PMID- 9555370
TI  - Collecting the Newborn Screening Test (NST), via the heel prick.

PMID- 9555372
TI  - Childbirth and the illness focus.
AB  - Childbirth is essentially women's business, a natural female act being performed
      since the beginning of mankind. However, as Western society has evolved, so too
      has the management of childbirth. It is the medical profession that has gained
      control of providing care for childbearing women, to the detriment of many
      women's experiences. The societal expectations on childbearing women, the
      iatrogenic effects of pregnancy being treated as an illness under the medical
      model, and the implications for the profession of midwifery will be discussed.

PMID- 9555373
TI  - Midwifery negligence: a case study.
AB  - A professional health practitioner can be found in law to be liable to compensate
      clients when the practitioner causes harm to the client through a negligent act
      or omission. To date, most health-related litigation has been directed toward the
      medical profession. A minority of cases are taken against health institutions
      with respect to nursing and midwifery practice. In recent years there have been a
      few cases in England in which midwifery practice has been an issue. The purpose
      of this article is to report on one such case. It is important for all midwifery
      practitioners to be aware of the facts and circumstances in which midwives have
      been found to be negligent, and the way in which the courts have dealt with the
      matters in dispute.

PMID- 9555374
TI  - Reforms affecting diverse populations.

PMID- 9555375
TI  - Family member discrepancies in report of a child's race.
AB  - This paper describes the types of discrepancies in self report of a child's race
      in a research study of cardiovascular health in school age children. Researchers
      sometimes make conclusions based on the percentage of subjects from each racial
      group included in the study. This is particular concern because in intervention
      studies researchers may report differing responses to treatment based on the race
      variable. This study increases awareness of issues surrounding assigning race of
      children participating in research studies.

PMID- 9555376
TI  - Protective factors within the family, and their role in fostering resiliency in
      African American adolescents.
AB  - Violence has reached epidemic proportions in the United States, with African
      American males residing in urban areas bearing the brunt of this epidemic. The
      violence permeating our society emanates from a variety of societal ills,
      including poverty, racism, substance abuse and exposure to violence.
      Traditionally, methods of research on adolescent violence have focused on an
      identification of associated risk factors. The majority of African American
      adolescents living in communities with widespread and chronic violence grow up to
      be law-abiding citizens. The reason for this may be due to resiliency within
      these adolescents. Resiliency has been defined as the ability to experience
      adverse circumstances and successfully overcome them. Resiliency is enhanced
      through three mechanisms identified as protective factors: individual
      characteristics/traits; familial traits; and extrafamilial relationships. The
      risks faced may be altered, and even ameliorated, through the presence of these
      protective factors. The purpose of this paper is to identify protective factors
      within the family that foster resiliency. Protective factors within the family
      may be categorized as having three broad characteristics: caring and support,
      high expectations, and encouragement of participation and involvement for the
      adolescent.

PMID- 9555377
TI  - Cultural implications for nursing care of the Amish.
AB  - The Amish are a conservative Protestant religious sect with a unique set of
      culture and traditions. In order to provide culturally appropriate and sensitive
      health care, it is imperative for nurses and other health care providers to have
      a basic understanding of variations of Amish lifestyle from other cultural
      groups. Application of Giger and Davidhizar's Transcultural Assessment Model
      provides information and nursing implications to assist nurses and other health
      care personnel when caring for Amish clients.

PMID- 9555378
TI  - A glance at Appalachia.
AB  - Appalachia is usually written about in romantic terms; rarely are the citizens of
      Appalachia portrayed as contributors to society. Appalachia is made up of many
      cultures--African American, European American, Melungeon, Native American and
      others. Appalachian cultures are not locked in a fixed state; one needs only to
      review the history of Appalachia to understand this concept (Tice & Billings,
      1991). Appalachian cultures are fluid and ever-changing. The cultures are
      expressed in literature, oral histories, music and regional history.

PMID- 9555379
TI  - Understanding the process.
AB  - The overall goal of the editors of the Journal of Holistic Nursing was to enhance
      the link between the professional literature and holistic nursing practice. To
      accomplish this goal, strategies were developed/refined that would increase the
      journal's acceptance into the clinical/academic marketplace. The purpose of this
      article is to produce a concise document that describes the publication process.
      The following topics are addressed: (a) the rationale for writing, (b) the
      publication requirements, (c) selecting a journal, (d) the peer review/evaluation
      process, and (e) the essential components of an article. The purpose of this
      editorial effort was to assist manuscript writers to become published authors.
      Hopefully, the activities of the editors and the contents of this article will
      facilitate the efforts of many aspiring authors.

PMID- 9555380
TI  - Inventory of professional activities and knowledge of a holistic nurse (IPAKHN).
AB  - In the development and administration of a certification examination in holistic
      nursing, an important issue is to ensure adequate content validity. Thus, the
      American Holistic Nurses' Association (AHNA) and the American Holistic Nurses'
      Certification Corporation (AHNCC), with the assistance of the National League for
      Nursing, conducted a practice analysis study to generate empirical data on the
      professional activities and knowledge required to practice holistic nursing on a
      day-to-day basis.

PMID- 9555381
TI  - Differentiating holistic practice and speculations for future directions.
AB  - Technological advances and economic, social, and cultural conditions have created
      a climate of change in health care. New roles and approaches are developing in
      relation to the holistic health movement. Within the holistic nursing community,
      three concepts of holistic practice have emerged. Differentiations among (a)
      certified holistic nurses, (b) practitioners of a healing modality, and (c)
      healers are presented to promote future discussion. As new roles must match a
      social need and become institutionalized to secure a professional role,
      speculations on possible directions for the certification in holistic nursing are
      presented.

PMID- 9555382
TI  - Humor and pain management. A review of current literature.
AB  - The purpose of this article is to provide a review of current literature related
      to humor and pain management. A brief review of the benefits of humor on the body
      is followed by a literature review of articles on humor and pain management,
      including research articles and scholarly articles on the topic. Research studies
      on the use of humor with both acute and chronic pain will be reported. The review
      of scholarly unresearched articles will include articles giving guidelines for
      humor use, suggested humor assessment guidelines, discussion of the nurse's role
      with humor use, and implementation strategies via humor carts and rooms.

PMID- 9555383
TI  - The meaning of diabetes. Significance for holistic nursing practice.
AB  - Recent research has raised questions about the validity and relevance of health
      practitioners' perspectives of diabetes and diabetes care. This article describes
      a qualitative research study that was undertaken to illuminate an insider's
      perspective of how Type I diabetes is meaningfully experienced. The results of
      this study reveal that although people with diabetes share a common disease, the
      meaning of that disease in people's lives is unique and varied. To provide
      holistic care, nurses must assist people in discovering and articulating the
      meaning of diabetes in their lives as well as acknowledging and attending to the
      significant elements within their experiences.

PMID- 9555384
TI  - [Respiratory therapy (physical therapy) in children with heart disease].

PMID- 9555385
TI  - [Long-term electrocardiography for the diagnosis of congenital and postoperative
      arrhythmias].

PMID- 9555386
TI  - [Temporary pacemaker therapy after heart surgery].

PMID- 9555387
TI  - [Psychosocial care of parents of children with heart disease].

PMID- 9555388
TI  - [The counseling team of the St. Anna Pediatric Hospital nursing service--a center
      for pediatric and adolescent care].

PMID- 9555389
TI  - [Giving competent care--where does one learn that?].

PMID- 9555390
TI  - [Practical training from the viewpoint of nursing students in Austria and
      Germany].

PMID- 9555391
TI  - [Integration of parents into German pediatric units--current problems and
      strategies for their management].

PMID- 9555392
TI  - [Transplantation legislation is now in force].

PMID- 9555393
TI  - [Basal stimulation in the premature].

PMID- 9555394
TI  - [More and less toxic plants. 36].

PMID- 9555395
TI  - [Nursing legislation--presentation report and commentary on the opinion "Public
      legal basis for the nursing profession in view of their range of duties"].

PMID- 9555396
TI  - A framework for managing risk.
AB  - Supervision aims to maintain standards, thereby reducing clinical risk. Katrina
      Neal warns that supervision records could be used in a court of law, so should
      not be written simply to let off steam.

PMID- 9555397
TI  - Lecturer-practitioners: serving two masters for a common cause.
AB  - Is the theory-practice gap being bridged now that lecturer-practitioner posts
      exist in many parts of the country? Jenine Willis finds out how some
      practitioners are coping with the demands of the job.

PMID- 9555398
TI  - Designing learning activities.
AB  - In the fifth part of this series on teaching skills, Dai Hall suggests some ways
      of organising your material when imparting information or when organising a
      discussion.

PMID- 9555399
TI  - Freedom and free will.

PMID- 9555400
TI  - What are 'rights'?

PMID- 9555401
TI  - Using technology for distance.
AB  - Internet-based distance education is in its infancy. As technology continues to
      develop and accessibility to the Internet grows, so, too, will delivery of
      educational materials via the Internet. In the meantime, the Wolfson Institute is
      taking the opportunity to learn how to harness this technology for educational
      purposes and to prepare for a future where education and technology move even
      closer together.

PMID- 9555402
TI  - What's the point of ... public health?

PMID- 9555403
TI  - Cervical screening programme omitted from article.

PMID- 9555404
TI  - Towards a national paediatric service.

PMID- 9555405
TI  - Grateful for help given, not disempowered.

PMID- 9555406
TI  - Workplace relations bill is anti worker.

PMID- 9555407
TI  - Nurses should speak in plain language.

PMID- 9555408
TI  - Blueprint lacks social analysis.

PMID- 9555410
TI  - Caring for the mentally ill.

PMID- 9555409
TI  - A tribute to Tama.

PMID- 9555411
TI  - Leading from behind.

PMID- 9555412
TI  - Seeing the whole picture. A gift from the sea.

PMID- 9555413
TI  - Seeing makes the difference.

PMID- 9555414
TI  - Seeing beyond.

PMID- 9555415
TI  - When I'm ok is not ok.

PMID- 9555416
TI  - Guiding the way.

PMID- 9555417
TI  - The gift of life.

PMID- 9555418
TI  - Administering drugs.

PMID- 9555419
TI  - Raising Te Runanga's profile.

PMID- 9555420
TI  - Will nursing exist tomorrow? A reprise.

PMID- 9555421
TI  - Ontology, epistemology, and methodology: a clarification.
AB  - The vistas of scholarly discourse in nursing are open to philosophical as well as
      scientific exploration. Careful attention to intersubjectivity in the use of
      language shared with other fields will continue to be a mark of nursing's
      rightful presence in an intellectual community committed to the pursuit of
      knowledge in the interest of advancing human welfare.

PMID- 9555422
TI  - Grounded theory research: its value for nursing.

PMID- 9555423
TI  - A nursing theory-guided model of health ministry: human becoming in parish
      nursing.

PMID- 9555424
TI  - A review of the power as knowing participation in change literature.
AB  - In the 15 years since the introduction of Barrett's theory of power as knowing
      participation in change and its accompanying measurement instrument, a rapidly
      growing number of research studies have been conducted using the theory and
      instrument. This article presents a critical review of this literature, as well
      as recommendations for further research.

PMID- 9555425
TI  - Methodological ponderings related to the power as knowing participation in change
      tool.
AB  - Based on 15 years of research using the Power as Knowing Participation in Change
      Tool, the authors summarize tool development, including reliability and validity,
      and discuss specific methodological issues and insights. These include clarity of
      instructions and complexity of language used in the PKPCT along with response
      set, norms, and sensitivity of the instrument to detect differences between
      groups. Problems of linear measurement are discussed along with the
      appropriateness of both qualitative and quantitative methods of studying power
      from the view of the science of unitary human beings. Recommendations for further
      psychometric studies of power are proposed.

PMID- 9555426
TI  - Evaluation of the human becoming theory in practice in an acute care psychiatric
      setting.
AB  - Using a descriptive evaluation research method, this study evaluated Parse's
      theory of human becoming in practice in the psychiatric setting. A pre- mid- post
      implementation design served to generate qualitative data from nurses, patients,
      unit nurse managers, hospital nurse supervisors, and nurse documentation that
      illuminated changes in the quality of nursing care on three diverse pilot units.
      Major themes of change supported by all data sources were shifting views of human
      beings, altered ways of listening, altered foci of nurse-person discussions, and
      personal transformations. Identified themes surfaced strikingly different
      qualities of change for each pilot unit. Recommendations related to the
      successful implementation of Parse theory-based practice are presented.

PMID- 9555427
TI  - Empirical verification of a theoretical model derived from the Roy adaptation
      model: findings from five studies.
AB  - This article presents a theoretical model derived from the Roy adaptation model
      and the findings of an empirical verification of this model from five studies.
      Four groups of subjects were included in the studies: informal caregivers of
      demented relatives at home, informal caregivers of psychiatrically ill relatives
      at home, professional caregivers of elderly institutionalized patients, and aged
      spouses in the community. In at least three studies, a number of theoretical
      propositions derived from the Roy adaptation model were supported using LISREL
      VIII, thus adding credence to some tenets of Roy's model. Particularly, the focal
      stimulus of perceived stress, the contextual stimulus of conflicts in the
      exchange of social support, and one component of the coping mechanisms (the
      passive/avoidance coping strategies) were positively linked directly or
      indirectly with psychological distress, which is an indicator of adaptation in
      the self-concept mode. Given their importance, these elements should be
      considered in the development of a middle-range theory of psychological
      adaptation derived from the Roy adaptation model.

PMID- 9555428
TI  - Homecare nurses face unique challenges in caring for patients with cancer.
AB  - Oncology care is going home. The changes in health care that have occurred during
      the past decade have significantly impacted the growth of home care. Factors that
      have contributed to this growth include prospective payments for hospital
      services to Medicare patients leading to a decreased length of stay, advances in
      the development of equipment for providing high-tech treatments in the home,
      changes in reimbursement from fee-for-service to managed care and capitation, an
      aging population, and improved survival rates for patients with chronic
      illnesses, including cancer.

PMID- 9555429
TI  - Leadership is about ordinary people doing extraordinary things.

PMID- 9555430
TI  - Describe a unique accommodation or creative solution you have used in caring for
      a patient at home.

PMID- 9555431
TI  - Can homecare services adequately address end-of-life issues?

PMID- 9555432
TI  - Immediate call to action: proposed regulation threatens cancer care delivery.

PMID- 9555433
TI  - Let's rediscover the joy of nursing.

PMID- 9555434
TI  - Highlights from the states: 1997.

PMID- 9555436
TI  - The personal and professional benefits of the ENT Nursing Foundation.
AB  - SOHN created the ENT Nursing Foundation at the 21st Annual Congress. This article
      describes the Foundation, the basics of its operation, and the benefits to SOHN
      and donors.

PMID- 9555435
TI  - Otorhinolaryngology nursing research priorities: results of the 1996/1997 SOHN
      Delphi survey.
AB  - This study was initiated by the Society of Otorhinolaryngology and Head-Neck
      Nurses, Inc. (SOHN) to establish research priorities for the specialty.
      Otorhinolaryngology (ORL) Nurses were asked to identify, rate, and rank
      priorities for ORL nursing research. The survey sample was gleaned from attendees
      at the 20th Annual SOHN Congress and Nursing Symposium plus a follow-up mailing
      to active SOHN members who did not attend. A decision-making method, the reactive
      delphi technique, was employed. Four rounds of soliciting opinions by
      questionnaires were completed. Data from each round were reviewed and analyzed by
      three ORL nurse investigators. The respondents were largely actively employed,
      female SOHN members who were seasoned nurses, experienced in ORL nursing. The
      majority were Registered Nurses (RN) or held Bachelor of Science (BSN) degrees.
      They were primarily employed as staff nurses in outpatient settings and working
      with a general otorhinolaryngology patient population of all ages. The fourteen
      priorities identified fall in the areas of patient outcomes (three), patient
      education (three), symptom management (two), patient self-care (two),
      psychosocial issues (two), and nursing care delivery (two), spanning the practice
      spectra of all ORL nurse generalists and subspecialists. The top five research
      priorities identified are; care of neck stomas and related equipment, quality of
      life in head and neck cancer patients, impact of managed care on ORL nursing care
      delivery, value of ORL specialty nurses/nursing units, and effective techniques
      to promote cessation of substance abuse in adolescents. This priority
      identification provides a baseline for the newly forming SOHN Foundation.

PMID- 9555437
TI  - The 21st annual SOHN congress.
AB  - In a recent Presidential Perspectives column (see ORL-Head and Neck Nursing, Vol.
      15, No. 3, Fall 1997, p. 4), Mary LeGrand described the impact that volunteerism
      can have on the success of an organization. The following article lends a prime
      example of how one SOHN member volunteers her services at both the local and
      national levels, donating her time and talents, reaping the rewards of her
      experiences, and ultimately sharing her thoughts in the following article.

PMID- 9555438
TI  - Who are pediatric nurse case managers ... and what are the hot issues?

PMID- 9555439
TI  - Little women: early menarche in rural girls.
AB  - Menarche, the first menstrual period, is a significant life event with important
      cultural, social, and personal implications. After noticing that several girls in
      a rural pediatric practice reached menarche at young ages, the researchers
      conducted a qualitative case study to investigate when menarche occurs and
      factors that may be associated with menarche onset. Four of the total of seven
      cases reached menarche before the average age of 12.8 years and had mothers who
      started at later ages. All four also experienced significant stressors just prior
      to onset. Lack of generalizability and the small sample disallow for any
      significant findings. However, the findings do indicate that menarche occurs in
      rural girls as young as age 9, creating implications for nurses in the areas of
      assessment, client teaching/counseling, and future research.

PMID- 9555440
TI  - Teaching and communication strategies: working with the hospitalized adolescent
      with pelvic inflammatory disease.
AB  - The increased incidence of sexually transmitted disease (STD) in the adolescent
      population has led the Centers for Disease Control and Prevention to highly
      recommend inpatient therapy for all adolescents with pelvic inflammatory disease
      (PID). This in turn has led to an increased need for nurses in inpatient settings
      to be skilled at providing sexuality education to adolescents with PID. The nurse
      needs a clear understanding of STD and PID, and the ability to communicate
      effectively with adolescents to help them make healthy decisions about their
      sexual behavior.

PMID- 9555441
TI  - Adolescent transitions: a nursing concern.
AB  - Adolescents with chronic conditions face unique challenges as they approach
      adulthood. Statistics on adults with disabilities indicate high rates of
      unemployment, few with college degrees, and limited options for community living.
      Until recently, efforts to facilitate successful transitions for adolescents with
      chronic conditions to adulthood have been limited. An awareness of some of the
      pertinent issues pertaining to adolescent transitions, especially those
      pertaining to health care, can assist the pediatric nurse in facilitating the
      transition to adult health care, career, employment, and community living.

PMID- 9555442
TI  - Impact of research on pediatric pain assessment and outcomes.
AB  - PURPOSE: Pediatric nurses from varied practice and educational backgrounds
      learned about research by doing a ward-based study. The aim of the study was to
      determine if regular assessment of children's pain would improve their pain
      management and postoperative progress. METHOD: Children, ages 5 to 17 years (n =
      36), measured their pain every 4 hours postoperatively using the Wong-Baker Faces
      Pain Rating Scale. Outcomes regarding amount of analgesic given, subjective pain
      reports, time and progress of ambulation, and length of hospital stay were
      compared with data from a retrospective chart-review of a control group (n = 50).
      FINDINGS: No statistically significant differences in these variables were found.
      An important clinical finding was that despite all children having prescribed PRN
      analgesic orders, one quarter of the children received no pain relief
      intervention. Also, one quarter of the children stated that their pain control
      was only partially effective. CONCLUSIONS: Study results reinforce findings
      reported in the literature regarding ineffective pain management in children, and
      highlight a need for improved nursing practice. Clinical significance was
      achieved in terms of staff learning of the research process, increased awareness
      of pediatric pain management practices, improved ward morale, and inter-agency
      sharing of resources.

PMID- 9555443
TI  - Public policy and child lead poisoning: implementation of Title X.
AB  - Nurses who care for pediatric patients in all settings must be aware of the
      critical effects of lead poisoning in children. Lead causes toxic effects in the
      human body, especially in children. These hazards have led to government
      involvement related to the issues of lead poisoning. Currently, governmental
      programs are set up under Title X: The Residential Lead Based Paint Hazard
      Reduction Act of 1992. However, the political changes and potential cuts in
      government spending may affect programs such as Title X. Because of this and
      their important role in child health, pediatric nurses should understand the
      political process, the implementation of such programs, and effects of potential
      funding cuts.

PMID- 9555444
TI  - Language development in bilingual children.
AB  - Bilingual language ability in children includes a wide range of verbal, written,
      and comprehension skills. Assessment of language development in bilingual
      children that is not individualized may yield inaccurate information and result
      in unnecessary referrals. Primary care nurses need to be aware of differences in
      language development between mono- and bilingual children in order to accurately
      assess their language skills.

PMID- 9555445
TI  - Effects of relaxation on anxiety in primary caregivers of chronically ill
      children.
AB  - PURPOSE: To evaluate the effects of self-applied breathing and guided imagery
      relaxation techniques, separately and in combination, and a reinforcement tool on
      primary caregivers (PCGs) coping with anxiety when caring for a chronically ill
      child. METHOD: Twenty PCGs, aged 25-57, of chronically ill children were randomly
      assigned to an experimental or control group. The State Anxiety Scale of the
      State-Trait Anxiety Inventory (Form Y) was used to measure state anxiety across
      three test administrations. FINDINGS: While there were no statistically
      significant changes in state anxiety, behavioral evaluations indicated that PCGs
      used both the self-applied relaxation techniques and the reinforcement tool more
      than twice daily. CONCLUSIONS: Relaxation techniques may be useful for those
      people caring for chronically ill children.

PMID- 9555446
TI  - Gender reassignment in children: ethical conflicts in surrogate decision making.
AB  - Parents, as surrogate decision makers for their infants, are generally expected
      by health care providers to act in the child's "best interest." However, when the
      wishes of the parents are contrary to those of the medical profession, an ethical
      dilemma occurs. Whose decisions are best for the infant? Whose recommendations
      are in the child's best interest? This article explores an issue that may not
      involve a life and death decision, but one in which the parents clearly refuse
      expert medical recommendations for what the providers believe are in the best
      interest of the infant. Specifically, the case study explores the parents'
      refusal to proceed with gender reassignment to female for their genetic XY baby
      born with micropenis and nonpalpable testes. The issue calls into question the
      possible limits of surrogate decision making. The ethical principles of
      beneficence, respect for persons, nonmaleficence, and justice are addressed in
      relation to this particular case.

PMID- 9555447
TI  - Ethical commentary on gender reassignment: a complex and provocative modern
      issue.

PMID- 9555448
TI  - Helping families mobilize their personal resources.
AB  - With changes in delivery of and payment for health care, hospital stays may be
      shorter and children may be going home sooner and sicker. Therefore, more care
      may be required at home. Even with access to a variety of services and resources
      in the community, families of medically fragile or chronically ill children can
      be overwhelmed and stressed. Relief can be provided to some degree if families
      creatively mobilize their own personal resources. However, for a variety of
      reasons, families may find it difficult to do this. While nurses and other health
      care professionals are accustomed to helping families find professional services
      and resources in the community, they can also be invaluable before discharge by
      assisting families with their personal resources--from giving encouragement and
      motivation to outlining practical planning steps. Pediatric nurses can use
      guidelines and a checklist to assist families with mobilizing their resources to
      ease the transition from hospital to home for the whole family.

PMID- 9555449
TI  - Consumer Bill of Rights: family-centered care.

PMID- 9555450
TI  - Changes proposed for RN licenses.

PMID- 9555451
TI  - Pediatric management problems. Plagiocephaly.

PMID- 9555452
TI  - Beyond hospital walls: educating pediatric nurses for the next millennium.
AB  - As pediatric units in acute care hospitals close, as lengths of stay shorten, and
      as increasing numbers of procedures are completed on an outpatient basis, faculty
      must find different learning experiences for their prelicensure students. Some
      programs have discontinued pediatric rotations, others are seeking clinical
      experiences in community settings. These community experiences hopefully produce
      a more well-rounded, globally thinking nurse to practice in the 21st century, yet
      they also raise a number of concerns.

PMID- 9555453
TI  - [Effects of nursing insurance on institutional care for the elderly].

PMID- 9555454
TI  - [Negative quality assurance by nursing insurances and social security].

PMID- 9555455
TI  - [Dynamic propositions in geriatric care].

PMID- 9555456
TI  - [Latex allergies as a problem in the health professions].

PMID- 9555457
TI  - [Transplantation legislation].

PMID- 9555458
TI  - [A glance into the European office of the World Health Organization].

PMID- 9555459
TI  - [Prevention of decubitus ulcers].

PMID- 9555460
TI  - [Specified tasks in nursing].

PMID- 9555462
TI  - [Three steps forward and two back].

PMID- 9555463
TI  - [Legal foundations for the health care market].

PMID- 9555464
TI  - [Quality assurance in operating room nursing].

PMID- 9555465
TI  - [Fed, clean and quiet in the nursing home. Effects of the 2. step in nursing
      insurance on geriatric care].

PMID- 9555466
TI  - [The limits of bearable treatment. May life-preserving measures be abandoned in
      terminal coma?].

PMID- 9555467
TI  - [Health care in Finnish schools].

PMID- 9555468
TI  - Covenant of caring.

PMID- 9555469
TI  - Succeeding against the odds. Interview by Nancy Evans.

PMID- 9555471
TI  - Research awards.

PMID- 9555470
TI  - Founders awards.

PMID- 9555472
TI  - Social action.

PMID- 9555473
TI  - A lot of care but little credit.

PMID- 9555474
TI  - [Public health: stakes in the changes in the 21st century].

PMID- 9555475
TI  - [The historical path of occupational health].

PMID- 9555476
TI  - [Tattooing in adolescence: using one's skin as parchment].

PMID- 9555477
TI  - [Refusal or impossibility to communicate?].

PMID- 9555478
TI  - [The kangaroo method: a bond in caring for prematures].

PMID- 9555479
TI  - [Dr. Pierre Balde, pediatrician. The Kangaroo method. Interview by Anne-Claire
      Delval-Motro].

PMID- 9555480
TI  - [Professor Jean-Pierre Relier, pediatrician. The Kangaroo method. Interview by
      Anne-Claire Delval-Motro].

PMID- 9555481
TI  - [A kit for scabies].

PMID- 9555482
TI  - [Hirschsprung's disease with all its features].

PMID- 9555483
TI  - [The story of Arthur ... or a mother's experience].

PMID- 9555484
TI  - [The reading lure or the book, the child and the hospital].

PMID- 9555485
TI  - [From the studio to the hospital].

PMID- 9555486
TI  - [A very specific nursing activity...].

PMID- 9555487
TI  - [End of a taboo: migraine is a very specific disorder].

PMID- 9555488
TI  - [The pluridisciplinary team: a complex requirement].

PMID- 9555489
TI  - [Ethics of care].

PMID- 9555490
TI  - [We like to talk a lot about health].

PMID- 9555491
TI  - [Health between dream and reality].

PMID- 9555492
TI  - [Cardiac insufficiency in the aged].

PMID- 9555493
TI  - [Prevention of malnutrition].

PMID- 9555494
TI  - [The dysharmonies of aging. A therapeutic place in a long-term facility].

PMID- 9555495
TI  - [Touch in nursing care].

PMID- 9555496
TI  - [Entering an institution. Anxieties of the elderly].

PMID- 9555497
TI  - [Self-help groups among nursing staff].

PMID- 9555498
TI  - [Wheelchair standards. How to choose one].

PMID- 9555499
TI  - [The Liliane Plaa Gerontology School].

PMID- 9555500
TI  - [The music therapist and the elderly].

PMID- 9555501
TI  - [The specific dependency allowance].

PMID- 9555502
TI  - [Sudden loss of autonomy. How to discuss the future of a patient with a
      cerebrovascular accident with his family].

PMID- 9555503
TI  - [The hairdresser].

PMID- 9555504
TI  - [Adolescent psychiatry. 40 years already...].

PMID- 9555505
TI  - [Adolescents and nursing care. Are there specific forms of care?].

PMID- 9555506
TI  - [A history of the nurses at the Clinique Dupre. 40 years already...].

PMID- 9555507
TI  - [Adolescent emergency and intensive care units. 10 years already...].

PMID- 9555508
TI  - [The role of the psychiatric nurse in the day hospital].

PMID- 9555509
TI  - [To be an actor in ones own life].

PMID- 9555510
TI  - [Counseling services in high schools and colleges].

PMID- 9555511
TI  - [Clinical nursing approach, beginning with daily discussions].

PMID- 9555512
TI  - [Adolescence, a special age. Summary of interventions].

PMID- 9555513
TI  - [Nursing care within the hospital unit].

PMID- 9555514
TI  - [ Emilio has hung himself...].

PMID- 9555515
TI  - [Prevention of drug dependence: how to do it].

PMID- 9555516
TI  - [Experience of pregnancy, delivery, motherhood and knowledge transfer in 3
      generations of mothers].
AB  - The purpose of the study was to describe how three generations of mothers have
      reacted to their pregnancies and deliveries and also how they feel about their
      maternity. Furthermore, the purpose was to illustrate the transfer of knowledge
      from one generation to another. Interviews have been made with three triads of
      generations, in all nine mothers. A phenomenological-hermeneutic onset has been
      chosen in order to analyse the narratives of the mothers. In the structural
      analyses the following themes came to hand: positive experiences/feelings,
      negative experiences/feelings, internal and external network and knowledge. The
      life-experiences of the maternity of the mothers were chiefly positive while
      experiences from pregnancy and childbirth were positive as well as negative. The
      knowledge of the mothers regarding childbirth and the bringing up of children
      were mostly conveyed in the everyday-contact during their early years, amongst
      mother-daughter-granddaughter. For the feeling of a successful experience during
      pregnancy, delivery and maternity, the internal network as well as the external
      turned out to be of great importance. In order to even better be able to provide
      for the needs of the expectant mothers or of those who have recently become
      mothers, an individual planning of care of both in- and out-patients within
      maternity- and childwelfare can be valuable.

PMID- 9555517
TI  - A follow-up study of the learning transfer process in further training of nursing
      staff.
AB  - The purpose of the study was to investigate whether the human and economic
      investment of resources in the further training of nursing and nursing assistants
      is justified. The study focused in particular on the transfer of knowledge from
      training course to working practice. It was carried out as a case study in
      Ringkobing County, Denmark, during 1993/94. The population consisted of 49 nurses
      and 49 nursing assistants. The study showed that the participants took a keen
      interest in the courses. The learning process was found relevant by the nurses,
      but not by the nursing assistants. Neither group found that their expectations of
      getting more knowledge were satisfied. With respect to job-behaviour, the study
      confirmed the hypothesis that the practising of the content of the course will
      depend on the support and interest of the head of the department towards a goal
      oriented development of competence and structure. If such support and interest is
      lacking, the course-participant will only change her own working practices,
      independent of the organizational structure.

PMID- 9555518
TI  - [Expectations and satisfaction of patients in home care--a qualitative study].
AB  - The purpose of this study was to illuminate the following questions, What do the
      district nurses think about the expectations of the patients during a home-visit?
      Which are the expectations of the patients concerning the home-visit done by a
      district nurse? The district nurses in a primary health care-centre and the
      patients that received home nursing in the primary health care district
      constituted the population. Ten nurses and twenty patients participated in the
      study. The method was qualitative with a hermeneutical approach. The tape
      recorded interviews were transcribed verbatim to constitute the empirical
      material for analysis and interpretation. The theoretical starting point was the
      concept of patient satisfaction. In the analysis and interpretation the following
      dimensions appeared; knowledge--professionalism, art of care--patient-district
      nurse relationship, participation and responsibility, continuity and
      availability. The result shows that the patients' expectations of the district
      nurses were extensively met and that they were satisfied with the home nursing
      care. The patients expected to meet a skilled district nurse who was kind, able
      to listen and reassuring. The district nurses think that the patients expect to
      meet a skilled person whose judgements are correct, who listens, shows respect
      and keeps her appointments.

PMID- 9555519
TI  - [The qualitative research interview as a method of approach to psychiatric
      nurses' professional life-world in community health services].
AB  - In the last decade the qualitative research interview, based on hermeneutic
      phenomenological understanding, has become a successfully used method in the
      Nordic countries, in the study of how persons experience their life-world (Ger.
      Lebenswelt) in social interaction and or in relation to their professions. The
      essential features of the qualitative research interview and its structural
      components have been quite well developed in these countries. Various aspects of
      the interpretation of interview texts have been theoretically analyzed from the
      hermeneutic-phenomenological viewpoint, and also its validity, reliability and
      fruitfullness have been carefully and constructively scrutinized. Necessary
      conditions to stimulate the 'right' use of qualitative research interview are,
      e.g., scientific articles which clearly describe how the method has been
      successfully applied on, inter alia, mental health and research dealing with
      public health. In this respect it is desireable to describe 1) how the choice of
      different strategies and techniques within the domain of qualitative approach are
      made and and illustrated, by means of concrete examples, and 2) to show how they
      are systematically and effectively applied in the research process. The purpose
      of this article should be seen against the background of 1) and 2), i.e., the
      article purports to show how the qualitative research interview was
      systematically used in studying psychiatric nurses' professional thoughts,
      experiences and practices in community psychiatric nursing, a study which
      attempted to do justice to the attainment of both goals 1) and 2).

PMID- 9555520
TI  - [Their own science? Analysis and discussion of Ingrid Heyman's thesis "Gange hatt
      till ..." nursing research comes of age in Sweden--nurses' papers 1974-1991].

PMID- 9555522
TI  - [Field study of nursing care quality. Interaction and asepsis in clinical
      practice].
AB  - Competence as communication skills and as skilled practice of asepsis were
      studied by observing four nurses while interacting with patients and performing
      intravenous procedures. Nurses were observed using sterile equipment for methods
      of intravenous therapy. Asepsis is performed frequently, but through
      misunderstanding in the learning of asepsis or improper model learning the nurses
      may establish incorrect routines. When performing procedures, unexpected factors
      can distract both the expert and the inexperienced, resulting in a failure to
      apply basic aseptic techniques. The nurses showed an interest in the patient by
      listening and giving responses. Nurses may control interactions with the patient
      by using undesirable communication skills which include incomplete sentences,
      incomplete explanations and closed questions. Asked to evaluate their own
      behavior, the nurses did not estimate whether or not the appropriate skills were
      applied in observed situations. To improve the quality of nursing care
      performance it is recommended to further develop and apply skill training
      programs.

PMID- 9555521
TI  - [Quality assurance in nursing in acute care using a Swedish modified version of
      the Rush-Medicus instrument].
AB  - The aim of the article is to describe experiences from a project on quality
      assurance of nursing care in a county hospital. Assessment and improvement of the
      quality of care were mainly based on an earlier developed modified Swedish
      version of the Rush Medicus Nursing Process Quality Monitoring Instrument (RMI
      MSV). Two hundred and forty patients and 57 registered nurses (RNs) representing
      surgical, medical and orthopaedic care units participated in the study, which was
      divided into two quality assessment occasions. An experiment-control design was
      used with intervention to the experiment units after the first quality assessment
      occasion. All the E-units improved their quality levels in almost all main areas
      in the second assessment occasion. The E-units together in relation to the C
      units together obtained statistically significant improvements (p < 0.05) in the
      main area concerning documentation (E-units minus C-units occasion 2 minus
      occasion 1). The overall experience is that the RMI-MSV can be used for quality
      assurance of nursing care in a Swedish acute hospital, but needs to be further
      refined.

PMID- 9555523
TI  - Nurses' perceptions of the content, relevance and usefulness of the quality of
      life concept in relation to nursing practice.
AB  - The aim of this study was to investigate how nurses define the quality of life
      concept and if they find it relevant and useful for their daily practice.
      Eighteen nurses recruited from a neurological and rheumatologic unit at a
      Norwegian University Hospital filled in a questionnaire consisting of four open
      ended questions in relation to the definition of quality of life, the concept's
      relevance for their daily practice, characteristics of a patient experiencing
      good vs. bad quality of life and ways to improve quality of life. The findings
      showed that nurses associated quality of life with the individual's experience of
      meaning in life. Meaning in life was associated with good mood, positive self
      concept, being solution-oriented, initiative to self-care and having a close
      relationship to significant others. Further, the nurses expressed that their way
      of being towards the patients in terms of give time, encourage, inspire
      confidence, be present and listen was the most important intervention to maintain
      or increase patients' quality of life.

PMID- 9555524
TI  - Parents' skin to skin holding of small premature infants: differences between
      fathers and mothers.
AB  - AIM: Both mothers and fathers should achieve early skin to skin holding of their
      small premature infants, despite the infants' need for breathing equipment,
      including respirator. If the mother needs to wait to hold her newborn due to her
      medical condition, this is not reason enough for the father also to wait.
      PURPOSE/QUESTION: Do fathers wait significantly longer post delivery to hold
      their small premature infants skin to skin (kangaroo) than mothers do? METHODS:
      Registration-schedule, existing sources of data, and interviews were used.
      FINDING/CONCLUSION: The time from birth (hours) until fathers held their small
      premature infants skin to skin was significantly different (p = 0.0004) compared
      to mothers. Fathers held their infants later than did mothers, despite the fact
      that fathers saw their infants before the mothers did. Compared to the mothers
      the average waiting time before fathers first held their infants skin to skin
      showed a difference of 120.9% (difference of the median).

PMID- 9555525
TI  - [Salutogenic model and utilization of the KASAM form (Sense of Coherence) in
      nursing research--a methodological report].
AB  - This paper presents psychometrical properties of the Swedish version of the Sense
      of Coherence (SOC) scale. The concept sense of coherence is proposed to explain
      successful coping with stressors and as being a stable trait of the individual.
      The stronger the SOC, the more successful coping and the more likely one is to
      have better health and quality of life. The data in this study has been obtained
      from five groups of healthy individuals and eight patient groups. The scores of
      the SOC scale did not change over time when studied after two, 12 and 18 months
      respectively. Weaker sense coherence was correlated to more self-rated anxiety,
      functional limitations especially those of a psychosocial character, and severe
      perception of symptoms, and to worse self-rated general health, and less
      motivation. It is suggested that the SOC scale could be of clinical use in
      assessing the need for nursing care.

PMID- 9555526
TI  - [Critical reflections on the uncritical use of measuring instruments: Example
      Sense of Coherence questionnaire].
AB  - This article presents a critical discussion of Antonovsky's salutogenic model,
      focusing on its instrumentalisation in the Sense of Coherence questionnaire and
      implications for health care research. The critical discussion is related to
      three themes: a. The divorce between theory and method, b. The Sense of Coherence
      questionnaire: a "supra-cultural instrument"? and c. Numbers, normality and the
      social construction of reality. The author concludes that extreme cautiousness
      and further study is necessary before the Sense of Coherence questionnaire should
      be considered adequate for use in applied clinical research.

PMID- 9555528
TI  - Transplantation.

PMID- 9555527
TI  - [Stigmatization, coping and handicap experience: interviews with middle-aged
      persons with progressive hearing impairment].

PMID- 9555529
TI  - Biology and management of acquired severe aplastic anemia.
AB  - Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder
      characterized by pancytopenia and a hypocellular marrow. Drugs, chemical
      exposure, radiation, and viruses are implicated as etiologic agents, although the
      majority of community-acquired SAA is idiopathic. Regardless of the inciting
      event, most cases of SAA result from immune-mediated destruction of bone marrow
      progenitor cells, which spares pluripotent hematopoietic stem cells. SAA is
      treated by either allogeneic bone marrow transplantation (BMT) or
      immunosuppressive therapy. BMT restores normal hematopoiesis and cures the
      disease in 60% to 80% cases, with the major causes of failure being graft
      rejection and graft-versus-host disease. Most patients treated with
      immunosuppressive therapy recover hematopoiesis sufficiently to not require
      transfusions and are free of infection, although in many, recovery is incomplete.
      Moreover, up to 50% of SAA patients successfully treated with immunosuppressive
      therapy relapse or develop a secondary clonal disorder, such as paroxysmal
      nocturnal hemoglobinuria, myelodysplastic syndrome, or leukemia. High-dose
      cyclophosphamide without BMT is capable of restoring normal hematopoiesis with
      little or no risk of relapse or secondary clonal disorders. A number of effective
      treatment options for the treatment of SAA are now available. The optimal
      approach for definitive management of SAA continues to evolve.

PMID- 9555530
TI  - Bone marrow transplantation for chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is a hematologic malignancy characterized by
      an initial chronic phase of expanded clonal myelopoiesis followed by inevitable
      progression to accelerated phase and finally to fatal blast crisis. Although
      interferon therapy results in hematologic control of disease in most patients and
      major cytogenetic responses in 30% to 35%, resulting in better survival than with
      conventional therapy with hydroxyurea or busulfan, most patients have residual
      disease detectable by molecular methods. Allogeneic bone marrow transplantation
      may cure selected patients with CML and should be considered early in the course
      of disease. Newer approaches to therapy include autografting using mobilized
      peripheral blood stem cells. Selection and expansion of nonleukemic progenitors
      may improve outcome following autologous transplantation. Advances in
      understanding of mechanisms of action of antisense oligonucleotides, ribozymes,
      and tyrosine kinase inhibitors and the immunologic responses to CML cells are
      also likely to lead to novel approaches to therapy.

PMID- 9555531
TI  - Quality of life following bone marrow transplantation.
AB  - Quality of life (QOL) studies in bone marrow transplantation (BMT) recipients are
      increasingly regarded as one of the ways to evaluate the outcome of BMT. Recent
      reports continue to detail acute and late psychosocial problems in BMT
      recipients. More and more longitudinal studies of QOL and comparisons of QOL
      outcomes after BMT or alternative nontransplant treatments are appearing in the
      literature. Several interventions that may promote positive effects on
      psychosocial adjustment are suggested: attention to patients' coping styles by
      the healthcare team, encouragement of aerobic exercise, attempts to lessen
      patients' levels of anxiety, and the presence of at least one staff member
      identified by the patient as an important source of support over time--all may
      have positive influences on QOL.

PMID- 9555532
TI  - Peripheral blood versus bone marrow for hematopoietic cell transplantation.
AB  - Peripheral blood stem cell transplantation is being used more frequently in both
      the autologous and allogeneic setting. The use of cytokines either alone or in
      conjunction with chemotherapy priming has made peripheral procurement of the stem
      cells through apheresis possible. Differences exist both in the composition of
      the graft and in subsequent posttransplantation immune reconstitution between
      peripheral blood stem cells and bone marrow. Reliable estimates of the
      comparative incidence of acute and chronic graft-versus-host disease following
      blood or marrow allogeneic transplantation are not yet available.

PMID- 9555533
TI  - Slow but real progress in the treatment of thoracic malignancies.

PMID- 9555534
TI  - Prevention of lung cancer.
AB  - Lung cancer chemoprevention continued to make progress in 1997. The incidence of
      tobacco abuse continues to slowly fall in the United States, and paralleling it,
      lung cancer incidence. Biomarkers of carcinogenesis and susceptibility continue
      to be an important area in identifying high-risk patients. The analyses of two
      major lung cancer prevention trials, beta-Carotene and Retinol Efficacy Trial
      (CARET) and Alpha-Tocopherol Beta-Carotene (ATBC), were also published this past
      year. Both found an increased incidence of lung cancer in individuals receiving
      beta-carotene. In both trials, heavy smokers seem to be the most adversely
      affected group. The mechanism of this increased incidence of cancer and total
      deaths still eludes investigators.

PMID- 9555535
TI  - Gene replacement strategies for lung cancer.
AB  - Considerable evidence has accumulated that cancer has a genetic origin based on
      the development of somatic mutations in families of genes responsible for
      critical functions of cellular DNA repair, growth control, and division.
      Restoration of the function of a single pivotal gene product appears sufficient
      to mediate antitumor effects that are potentially clinically significant. For
      example, restoration of wild-type p53 function in the cancer cell by gene
      transfer is sufficient to cause either cell-cycle arrest or apoptosis. This
      effect is not restricted to p53 but has been observed for oncogenes and other
      tumor suppressor genes as well. Genes can be delivered with sufficient efficiency
      by direct intratumoral injection to mediate tumor regression as shown in
      preclinical studies and phase I clinical trials in non-small cell lung cancer.
      Although clinical trials of gene replacement are in the earliest stages, this
      treatment offers a unique mechanism of action with a potentially high therapeutic
      index.

PMID- 9555536
TI  - Current therapy of small cell lung cancer.
AB  - This article reviews the most important recent clinical trials on the treatment
      of small cell lung cancer (SCLC). Two randomized studies addressing the timing of
      thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the
      two studies (n = 103), a survival benefit was associated with initial versus
      delayed radiotherapy. No survival differences in the larger study of the two
      studies were detected, which compared alternating with sequential delivery of
      radiotherapy (n = 335). The optimal way to deliver radiotherapy still must be
      defined. Two small, randomized studies on dose intensity with the use of growth
      factor support in patients with extensive disease reached conflicting results.
      Two randomized trials including patients with poor prognosis were discontinued
      prematurely, owing to interim analyses reporting a significant disadvantage in
      survival associated with oral single-agent etoposide compared with intravenous
      multiagent treatment. Thus, oral etoposide has a very limited role as single
      agent treatment in the palliative setting. Convincing data have emerged regarding
      the camptothecins. Randomized studies of both the camptothecins and the taxanes
      in combination with established drugs are awaited with interest. Unfortunately,
      too many studies still lack sufficient statistical power, and large randomized
      studies are needed.

PMID- 9555537
TI  - Enhancing the role of radiotherapy in non-small cell lung cancer.
AB  - Radiation therapy plays an important role in the treatment of patients with
      unresectable non-small cell lung cancer. Local control rates with past radiation
      therapy techniques have been poor, in the range of 10% to 15%. Recent advances in
      dose planning and delivery, as well as radiation biology, offer the promise of
      improved control and better protection of dose limiting normal tissues.

PMID- 9555539
TI  - Melanoma and other skin neoplasms.

PMID- 9555538
TI  - Surgical management of pulmonary metastases.
AB  - The management of pulmonary metastases remains controversial. More information is
      available, however, on outcomes in larger series of patients undergoing
      metastasectomy as well as the indications for the procedure. The role of video
      assisted thoracic surgery for the diagnosis and management of these patients is
      being scrutinized carefully. Isolated perfusion techniques for treating patients
      with unresectable pulmonary metastases have been applied in phase I and II trials
      at selected institutions. More data regarding clinical outcomes are necessary,
      however, before widespread adaptation of this experimental form of treatment is
      accepted as standard practice.

PMID- 9555540
TI  - Modifying the criteria of the American Joint Commission on Cancer staging system
      in melanoma.
AB  - The currently used staging system in melanoma has not been significantly modified
      since 1988. While this four-stage system effectively stratifies patients into
      prognostic groups, additional discriminating criteria have been reported that is
      not presently incorporated in the staging system. The following additions and
      modifications are suggested based on a review of the recent literature: 1) for
      stage I and II patients, Clark's level of invasion is only predictive in patients
      with melanomas less than 1 mm, the best statistical fit for tumor thickness
      cutoffs are less than 1 mm, 1 to 2 mm, 2 to 4 mm, and greater than 4 mm, and
      ulceration should be included as part of the staging system; 2) in stage III
      patients, the presently used criteria of 3 cm in size needs to abandoned and
      replaced by the number of lymph nodes involved and the number of lymph node
      basins involved; and 3) local recurrence presenting as local metastases and
      satellite disease represent a biologic continuum of regional lymphatic
      dissemination and should both be classified in the stage III prognostic groups.
      These modifications, if accepted, should provide the ability to better stratify
      patients for future adjuvant therapy trials.

PMID- 9555541
TI  - The role of the pathologist in the diagnosis of melanoma.
AB  - The pathologist plays a vital role in patients with malignant melanoma.
      Dermatologists, surgeons, and oncologists must rely on the pathologist for
      accurate and complete diagnoses. Although most melanomas can be easily recognized
      with routine histopathology, special stains, including immunohistochemistry, may
      be necessary to differentiate melanoma from other cutaneous malignancies.
      Likewise, there are benign entities that can mimic melanoma microscopically,
      including Spitz nevi, pigmented spindle cell nevi, deep-penetrating nevi, and
      Monsel's reaction. Recognition of these entities is important to avoid
      unnecessary surgery, testing, adjuvant therapy, and unnecessary concern by the
      patients and their families. In addition to making an accurate diagnosis, the
      pathologist should report prognostic histologic attributes that may influence
      therapy and follow-up care for these patients. These histologic features should
      be recorded in the pathology report. This chapter provides a brief review of the
      most important histologic attributes that should be identified and reported by
      the pathologist.

PMID- 9555542
TI  - Use of biological response modifiers in the treatment of cutaneous T-cell
      lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) is typically a skin-infiltrating, clonal
      proliferative disorder of CD4+ T cells that exhibit a T-helper type 2 cytokine
      phenotype. Therapeutic decisions are based on the extent of disease and the
      observations that host-antitumor responses occur and that these responses may be
      blunted by the immunosuppressive cytokines produced by the malignant T cells.
      Biologic response modifiers, which may enhance cell-mediated immunity and
      antitumor responses, are active agents in the treatment of CTCL. The rationale
      and use of biologic response modifiers to treat CTCL are reviewed in this
      article.

PMID- 9555543
TI  - Transplantation.

PMID- 9555545
TI  - Melanoma and other skin neoplasms.

PMID- 9555544
TI  - Lung and mediastinum.

PMID- 9555546
TI  - Urinary incontinence in elderly women.

PMID- 9555547
TI  - The need for an international classification of benign prostatic hyperplasia.
AB  - An international classification of patients suffering from benign prostatic
      hyperplasia is essential, as we are currently unable to categorize patients there
      by allowing application of the most appropriate treatment as a function of
      selected items. We have adopted 4 items: weight of the prostate (P); quality of
      life index (Q); international prostatic symptom score (S), and maximum flow rate
      (F). 112 patients were analyzed according to this classification and the results
      are presented. We have tried to develop a simple, easy to remember classification
      in order to easily allocate a given patient to a particular category. This
      proposed classification corresponds to a real 'Prostate Who's Who', which should
      be evaluated and improved to act as a working basis for an international
      classification of benign prostatic hyperplasia.

PMID- 9555548
TI  - Clearance of free and total serum PSA after prostatic surgery.
AB  - INTRODUCTION: Although the biology and sites of secretion of PSA are well known,
      its pharmacokinetics are still unclear. This study analyzes the differences
      between the clearance of total and free serum PSA following open surgery for BPH
      and radical prostatectomy. METHODS: Free and total PSA were measured in 27
      patients submitted to radical prostatectomy for clinically localized prostate
      cancer (group I) and in 27 patients submitted to open surgery for BPH (group II).
      In both groups, the clearance of free and total PSA was studied. RESULTS: Group I
      the mean half-life was 1.416 +/- 0.723 days for free PSA and 2.43 +/- 0.688 days
      for total PSA. After prostate removal, free PSA showed a marked increase. Group
      II-the mean half-life of free PSA was 2.157 +/- 1.792 days and 3.391 +/- 2.337
      days for total PSA. CONCLUSIONS: The increase in free PSA shortly after
      manipulative procedures of the prostate was higher than the increase in total
      PSA. Serum clearance of free PSA after eradicative prostatic surgery was related
      to the indication and type of procedure used.

PMID- 9555549
TI  - Effect of digital rectal examination and flexible cystoscopy on free and total
      prostate-specific antigen, and the percentage of free prostate-specific antigen.
      Differences between two PSA assays.
AB  - OBJECTIVE: To determine the effect of prostate manipulations on free PSA, total
      PSA and the percentage of free PSA using an equimolar and nonequimolar PSA
      assays. METHOD: A total of 67 men were studied. Blood samples were obtained
      before and 45-60 min after two different prostatic manipulations: DRE from 45
      patients and flexible cystoscopy from 22 patients. Total PSA (t-PSA) was assayed
      with a non equimolar method using the Cobas Core PSA kit from Roche (Cobas Core
      PSA) and an equimolar method using the Immulite 3rd-generation PSA kit from DPC
      (Immulite-PSA). Free PSA (f-PSA) was quantified with an Immulite free PSA kit. We
      obtained two f-PSA/t-PSA ratios dividing the f-PSA by both t-PSA (Cobas Core-PSA)
      and t-PSA (Immulite-PSA). RESULTS: The Cobas Core-PSA yielded higher values than
      Immulite-PSA and the baseline percentages of free PSA were different depending on
      the method used. Both t-PSA values were increased after DRE and flexible
      cystoscopy from the baseline although the increase of Cobas Core-PSA was much
      higher than Immulite-PSA. Also the f-PSA was increased after the two
      manipulations. The f-PSA/t-PSA ratio (Cobas Core-PSA) remains at the baseline
      whereas the f-PSA/t-PSA ratio (Immulite-PSA) had an important increase from the
      baseline. CONCLUSION: The effect of DRE and flexible cystoscopy is different
      depending on the PSA assay used. The data from studies which are carried out in
      relation with the molecular forms of the PSA are not interchangeable if they are
      performed with different PSA methods (equimolar and nonequimolar). The serum
      samples should precede any prostate manipulation in all investigations related to
      PSA molecular forms.

PMID- 9555550
TI  - Gleason scores from prostate biopsies obtained with 18-gauge biopsy needles
      poorly predict Gleason scores of radical prostatectomy specimens.
AB  - OBJECTIVES: Prostate cancer is the most frequent cancer among men in the US.
      Histological grading is an important part of the diagnostic evaluation aside from
      clinical staging and serum PSA. The most commonly used grading system is the one
      described by Gleason. From a prognostic point of view, it is of considerable
      interest to know how accurate the needle biopsy Gleason score is in predicting
      the final score of the radical prostatectomy specimen. From an outcome research
      point of view, it is important to recognize that a stratification of patients by
      Gleason score may prove correct in patients undergoing radical prostatectomy,
      while in patients undergoing radiation or conservative management some of the
      well-differentiated cancers could actually be moderately and poorly
      differentiated, and some of the moderately differentiated might be poorly
      differentiated, thus favoring radical prostatectomy in a direct comparison of
      treatment efficacy. We aimed to determine (1) whether such undergrading exists,
      (2) what the magnitude of the bias is, and (3) whether it is common and similar
      in different institutions. MATERIALS AND METHODS: We retrospectively reviewed the
      records of 415 patients who underwent radical prostatectomy in three Dallas area
      hospitals, excluding patients who received neoadjuvant therapy prior to surgery.
      Data of Gleason grades and score were collected from the needle biopsy and the
      radical prostatectomy specimen. Analysis was done using three categorization
      schemes for mild, moderate and poor differentiation for the three individual
      hospitals and the entire group. RESULTS: The most common Gleason score by needle
      biopsy and prostatectomy was five. 37.2% of all patients had no change in score
      assignment, while 12.7% were 'overgraded' and 50.1% 'undergraded' by needle
      biopsy. The most common undergrading was by 1 or 2 score points. Only 23.7% of
      the category 'well' cancers remained so after surgery. Between 65.0 and 88.4% of
      the category 'moderate' cancers remained so after surgery. To determine the
      degree of agreement between needle biopsy and surgery category, kappa statistics
      were employed. The kappa value ranged from 0.148 to 0.328 for all categories and
      classification schemes indicating poor reproducibility. Serum prostate-specific
      antigen was not helpful in predicting Gleason score upgrading. CONCLUSIONS:
      Independent of the setting, about 50% of all Gleason score assignments made on
      needle biopsy specimen are revised in the direction of a worse score/category. It
      is important for clinicians to realize this phenomenon when consulting with
      patients regarding treatment choices if the grade is taken into consideration.
      For outcome research purposes, it is important to realize that this introduces a
      bias into direct comparisons between surgical and nonsurgical (radiation and
      watchful waiting) series favoring the outcomes of surgical series as the
      nonsurgical series suffer from a less favorable patient mix.

PMID- 9555551
TI  - Prognostic significance of seminal vesicle invasion on the radical prostatectomy
      specimen. Rationale for seminal vesicle biopsies.
AB  - OBJECTIVE: The prognostic significance of seminal vesicle invasion on the radical
      prostatectomy specimen was evaluated according to the proximal or distal site of
      this invasion. MATERIALS AND METHODS: 52 consecutive patients undergoing radical
      prostatectomy for stage pT3b N0 M0 prostatic cancer were classified into two
      groups: group A (18 patients): patients with invasion limited to the proximal
      part of the seminal vesicles (stage T3b limited); group B (34 patients): patients
      with invasion extending to the free part of the seminal vesicles (stage T3b
      extensive). The PSA progression-free curves were compared between the two groups.
      A multivariable regression model was performed to determine independent
      prognostic factors. RESULTS: Overall, the 5-year PSA progression free rate of the
      52 patients was 14.4%. The 5-year PSA progression-free rate of the patients in
      group A was 45.4 vs. 4.2% at 4 years in group B (p = 0.0004). The stage of
      seminal vesicle invasion and the Gleason score were the only independent
      predictive factors of PSA progression (p = 0.02 and p = 0.04, respectively).
      CONCLUSIONS: The prognostic significance of seminal vesicle invasion is not
      constant and depends on the site of invasion. Preoperative seminal vesicles
      biopsies can select patients with invasion extending to the free part of seminal
      vesicles and who have a poor prognosis in terms of PSA progression after radical
      prostatectomy.

PMID- 9555552
TI  - Comparative analysis of MiB1 and p53 expression in human bladder tumors and their
      correlation with cancer progression.
AB  - Expression of p53 and MiB1, markers of tumor proliferation, was evaluated in
      human bladder tumors, and correlated with ploidy and cancer progression in 83
      consecutive patients. Transurethral resection of a newly diagnosed bladder tumor
      was performed in 73 cases, and systematic bladder biopsies were performed in 10
      cases after bacillus Calmette-Guerin (BCG) treatment. p53 and MiB1 expression
      were performed by an immunohistochemical technique and the ploidy was determined
      on a frozen fragment of the tumor. p53 expression was correlated in relation to
      grade, stage and combination of grade and stage. MiB1 expression was correlated
      with cytological grade, and a significant difference was demonstrated between pT0
      and pTa, pTa, and pT1, pTa and pT2 tumors but not between pT1 and > or = pT2
      tumors. A discordance was observed for the comparison of p53 and MiB1 values,
      stage by stage, suggesting that these two techniques are independent of each
      other. A larger proportion of aneuploid tumors were positive for p53 and MiB1
      (64.8 vs. 86.5%, respectively), but p53 and MiB1 immunostaining were not better
      indicators than ploidy alone to predict cancer progression.

PMID- 9555553
TI  - A randomized study of short-versus long-term intravesical epirubicin instillation
      for superficial bladder cancer. Nagoya University Urological Oncology Group.
AB  - OBJECTIVE: A prospective randomized study was undertaken to determine whether
      prophylactic maintenance instillation of epirubicin following induction treatment
      is beneficial in patients with superficial bladder cancer. PATIENTS AND METHODS:
      One hundred and forty-eight patients with resectable superficial bladder cancer
      (Ta-1, single, multiple, primary or recurrent with, however, no recurrence during
      the last year) were enrolled in this study. In both arms, epirubicin (40 mg/ml in
      normal saline) was administered six times within 4 weeks after a transurethral
      resection of the bladder tumor(s). In arm A, the patients received 11 additional
      monthly instillations of epirubicin. RESULTS: Of the 148 patients, 138 (93.2%)
      were eligible and followed for an average of 29.6 months. 93 (67.4%) had a
      solitary tumor. No significant difference in the recurrence-free curve was
      observed between the two arms (p = 0.62). The recurrence rate per year was 0.16
      in arm A and 0.17 in arm B. Toxicity included vesical irritability in 10 (7.2%)
      and hematuria in 1 patient. No significant difference in the frequency or degree
      of toxicity was observed between the two arms. CONCLUSION: These data suggest
      that maintenance instillation of epirubicin does not reduce superficial bladder
      cancer recurrence.

PMID- 9555554
TI  - Changes in erectile response to repeated audiovisual sexual stimulation.
AB  - OBJECTIVES: To determine changes in erectile response to repeated audiovisual
      sexual stimulation in patients with psychogenic impotence and normal men.
      METHODS: The same erotic video was shown to 45 men (20 patients with psychogenic
      impotence and 25 normal men) for 3 consecutive days. Their erectile responses
      during the audiovisual stimulation were monitored using RigiScan (Dacomed,
      Minneapolis, Minn., USA), and the maximal rigidity of erection, sustained for
      more than 5 min, was measured. The rigidities on the first, second and third days
      were comparatively analyzed. Whether previous multiple viewings of the erotic
      movie and previous exposure to the same or a similar movie influenced the
      erectile response were also evaluated. RESULTS: Rigidity on the third day was
      significantly decreased compared to that on the first day in both patients with
      psychogenic impotence and normal controls (p < 0.05), regardless of the frequency
      of previous viewings and the previous exposure to a similar movie. Rigidity on
      the first day was significantly lower in the group with multiple viewings than in
      the group with fewer viewings (p < 0.05). CONCLUSIONS: Real-time monitoring of
      penile erection during audiovisual sexual stimulation may result in false
      negative responses when patients are repeatedly exposed to the stimulation.

PMID- 9555555
TI  - The effect of re-dosing of vasodilators on the intracavernosal pressure and on
      the penile rigidity.
AB  - PURPOSE: To study the effect of re-dosing of vasodilators on cavernous smooth
      muscle relaxation. METHODS: The intracavernosal pressure (ICP) was measured in 48
      patients undergoing an intracavernosal injection test followed by gravity
      cavernosometry before and after administration of 1 or 2 booster injections with
      20 micrograms prostaglandin E1 after an initial injection of a trimix of
      vasodilators. When submitted to Duplex scanning on another occasion, the
      injection of the trimix was followed by squeeze of the corpora. The occurrence of
      clinical full erection during the examinations was registered. RESULTS: The mean
      values of the ICP changed little, albeit statistically significant, after the
      first booster injection (+3.47 mm Hg) but not after the second one. With
      cavernosometry, a false diagnosis of cavernous leakage was made in at least 14
      patients. During Duplex scanning, after the corpora were squeezed, 12 patients
      developed a clinical full erection, but none did during the intracavernosal
      injection test, even after re-dosing. A minimal drop in blood pressure was
      observed in 15 subjects after a booster injection. CONCLUSIONS: Administration of
      booster injections of 20 micrograms prostaglandin E1 after an initial injection
      of trimix did not induce sufficient cavernous smooth muscle relaxation. Squeezing
      of the corpora after injection of trimix was more successful.

PMID- 9555556
TI  - Comparative analysis of bladder neck suspension using Raz, Burch and transvaginal
      Burch procedures. A 3-year randomized prospective study.
AB  - PURPOSE: Ever since Pereyra described needle suspension of the bladder neck for
      the treatment of stress urinary incontinence in women, numerous modifications
      have been presented. There were variations in the success reported by different
      authors. We report 3-year follow-up results in 146 women operated on for stress
      urinary incontinence using Raz, Burch and our own new procedures. MATERIALS AND
      METHODS: During a 5-year period, 146 women were operated on for genuine stress
      urinary incontinence. Using the method of Raz, and transvaginal Burch as well as
      the Burch retropubic urethropexy, a modified bladder neck suspension was
      performed in 46 (32%), 44 (30%) and 56 (38%) patients, respectively. In all
      patients a prior gynecological or urological operation for urinary incontinence
      and a clear neuropathic condition had been excluded before surgery. The routine
      diagnostic procedure consisted of multichannel cystometry, voiding
      cystourethrography, infusion urography and cystoscopy. A pressure-flow
      electromyography study was done in patients with a residual volume greater than
      50 ml following voiding. The operations were performed by the same surgeon
      (I.G.). Initial follow-up was done after 12 months and then every year. RESULTS:
      Urodynamic testing did not reveal significant differences between Burch and Raz
      (p = 0.2652), Raz and transvaginal Burch (p = 0.5745) as well as between Burch
      and transvaginal Burch procedures (p = 0.7602; Fisher's exact test). Three years
      after surgery, 50 of 56 (89.3%; Burch procedure), 37 of 46 (80.4%; Raz
      modification) and 38 of 44 patients (86.4%; transvaginal Burch) were continent.
      CONCLUSIONS: There is no reason (except patient condition) to prefer any of the
      numerous modifications of bladder neck suspension. We believe that the success of
      the operation lies in adequate mobilization of the bladder neck and urethra as
      well as in a surgeon's familiarity with the procedure.

PMID- 9555557
TI  - Laparoscopic adrenalectomy. Comparison of the transperitoneal and retroperitoneal
      approach.
AB  - OBJECTIVES: The efficacy of transperitoneal (TP) and retroperitoneal (RP)
      laparoscopic adrenalectomy was compared. METHODS: Twenty-nine patients (male: 13;
      female: 16) with benign adrenal tumor were evaluated in this study. Seventeen
      were treated with the TP, and 12 with the RP approach. RESULTS: Convalescence for
      the TP group took longer than that for the RP group and postoperative pain was
      stronger for the TP than the RP group, although the difference was not
      significant. In addition, the amount of blood loss was larger for the TP than the
      RP group. When the cases were divided according to site of disease, the operating
      time for the right side was 351 min for the TP group and 347 min for the RP
      group, while that for the left side was 528 min for the TP group and 267 min for
      the RP group. CONCLUSIONS: Therefore, we recently prefer the RP approach for left
      adrenalectomy, but consider either approach suitable for the right side. The
      reason for this preference is that shortening the operating time is most
      important, also in the case of laparoscopic adrenalectomy because of the
      resulting reduced blood loss and the patients' early convalescence.

PMID- 9555558
TI  - Rotundovaginopexy in orthotopic ileal neobladder following radical cystectomy in
      women.
AB  - PURPOSE: The technique of rotundovaginopexy after cystectomy in females is
      described. MATERIALS AND METHODS: Four cases, two of them with over 12 months of
      follow-up are presented in whom this technique was used. RESULTS:
      Rotundovaginopexy stabilizes the vagina and thus prevents descent of the
      neobladder. Therefore the position of the neobladder is truly orthotopic. Thus
      continence and micturition are optimized. CONCLUSIONS: With this technique a
      truly orthotopic neobladder position can be achieved. The technique is simple to
      accomplish, even if hysterectomy has been performed long before. Pouchocele with
      possible complications such as secondary increased post-void residuals or
      incontinence may be avoided.

PMID- 9555559
TI  - Maximum efficacy of finasteride is obtained within 6 months and maintained over 6
      years. Follow-up of the Scandinavian Open-Extension Study. The Scandinavian
      Finasteride Study Group.
AB  - OBJECTIVES: To study the long-term efficacy and safety of the drug finasteride
      (Proscar) for benign prostatic hyperplasia and to evaluate whether an improved
      effect beyond 1 year was due to continuous selection of 'responders'. We also
      wanted to investigate whether drop-outs differed in short-term responses to those
      completing the trial. METHODS: A total of 182 patients were enrolled in a double
      blind randomized multicenter study with the drug finasteride. After 6 months, all
      patients were treated with active drug for up to 6 years. Ninety-nine of the
      patients (54.5%) were still in the trial at its closure. RESULTS: Patients
      treated with active drug had a decrease in prostate size of around 27% at 6
      months, a figure reached by the ex-placebo group at 12 months. At 6 years, both
      groups had a reduction in prostate size of 21% as measured from baseline. At 6
      months, urinary flow had improved by a mean of 2.4 ml/s in the finasteride group
      and reached an improvement of 2.8 ml/s in the ex-placebo group at 12 months. At 6
      years, the flow had improved by 2.2 ml/s in both groups combined as compared to
      baseline data. The symptom score was improved by 3.4 points in the finasteride
      group at 6 months and by 2.6 points in the ex-placebo group at 12 months; both
      values were then maintained over 6 years. CONCLUSION: In responders (those
      completing the 6-year trial), finasteride appeared to be a safe drug which
      reduced the prostate size by 20-25% within 6 months, with a simultaneous 30%
      improvement of objective and subjective symptoms and a 2.2 ml/s improvement in
      urinary flow rate. The improvements were maintained for at least 6 years;
      however, further improvement beyond 6 months of therapy was not likely to occur.

PMID- 9555560
TI  - Vasal reanastomosis using fibrin glue combined with sutures: which combination of
      sutures in a delayed protocol? Experimental study in rats.
AB  - OBJECTIVES: The actual number of transmural sutures needed to ensure a successful
      fibrin-glued vasovasostomy is a key study parameter of the few experimental works
      already published. The present work was done to evaluate fibrin-glued
      vasovasostomy in rats in combination with only 2 transmural sutures. We compared
      the results to our previous study in which we demonstrated the efficiency of a
      combination of the use of fibrin glue with 3 sutures in comparison with a
      conventional microsurgical technique. MATERIALS AND METHODS: Twenty Sprague
      Dawley rats underwent bilateral vasectomy followed 2 weeks later by bilateral
      vasovasostomy using fibrin glue combined with 2 transmural sutures. Each animal
      was sacrificed 7 weeks postoperatively after a 3-week mating period with a
      Sprague-Dawley female rat, the vasal specimens were evaluated for sperm granuloma
      formation. Mean operative time and fertility rates were recorded. RESULTS: The
      combination of fibrin glue with 2 transmural sutures gave evidence of less
      successful performances than the combination with 3 transmural sutures and the
      conventional microsurgical technique for all parameters evaluated but the mean
      operative time. CONCLUSION: Our study underlines the need for a third transmural
      suture placed 120 degrees apart from the others when performing a fibrin glue
      delayed vasovasostomy. This allows a better vas lumen opening at the anastomotic
      site and therefore a more efficient vasal anastomosis in a delayed protocol.

PMID- 9555561
TI  - Repeated urine analysis in patients with calcium stone disease.
AB  - OBJECTIVE: To study the variability in urine composition with respect to factors
      of importance for the calcium salt crystallization process and to test the
      reliability of using one or several urine samples in the clinical evaluation.
      PATIENTS AND METHODS: Twelve patients collected 16-hour daytime and 8-hour night
      urine samples during 4 days of the same week. The urine was analysed for calcium,
      oxalate, phosphate, magnesium, citrate and pH, and the ion activity products of
      CaOx [AP(CaOx) index] and CaP were calculated. The risk of CaOx crystallization,
      as well as the inhibition of CaOx crystal growth and aggregation, were assessed.
      RESULTS: There was a good correlation between estimates of the AP(CaOx) index in
      the different samples, as well as between the AP(CaOx) index and the direct
      assessment of the risk of CaOx crystallization in the night and daytime urine
      samples. There was, however, a pronounced intra-individual variation of all
      variables and parameters. With the assumption that an abnormality would appear in
      at least one of the four samples, we found that in more than 80% of the cases,
      two 24-hour (16 + 8 h) urine samples were sufficient to establish whether the
      patient had a normal or an abnormal urine composition. CONCLUSION: Urine samples
      collected during two 24-, 16- or 8-hour periods appear to be useful for detecting
      biochemical abnormalities considered of importance for CaOx stone formation.

PMID- 9555562
TI  - Results of extracorporeal shock wave lithotripsy in the pediatric age group.
AB  - OBJECTIVE: In this study we aimed to show the efficacy of extracorporeal shock
      wave lithotripsy (ESWL) for urinary stone disease in the pediatric age group and
      to evaluate the complications encountered after the treatment. METHODS: 67
      children with 109 stones underwent ESWL, using a Dornier MPL 9000 lithotriptor.
      Styrofoam boards were used to protect the lungs. KUB and chest radiographs were
      taken on the day after treatment. If stone-free status was achieved, the patient
      was followed with ultrasonography and urine analysis every 6 months for 2 years.
      If fragments < 4 mm were present, follow-up was repeated every 3 months. RESULTS:
      Stone size ranged from 0.5 to 3.5 cm. 71 renoureteral units underwent a total of
      129 ESWL sessions. Retreatment was required in 28 patients. The mean number of
      sessions per unit was 1.8. A stone-free status was achieved in 60 renoureteral
      units. The overall success rate was 88.6%. The composition of the stone was mixed
      calcium oxalate and phosphate in the majority of the patients. Auxiliary
      procedures used were push-back, ureteroscopic stone removal, and open surgery.
      Hematuria, colics and fever over 38 degrees C were the complications encountered
      after the treatment. CONCLUSIONS: ESWL is the first-line treatment for renal and
      upper ureteral calculi. However, larger stones which will require several ESWL
      sessions and consecutively increased number of shock waves are best treated with
      percutaneous nephrolithotomy plus ESWL. Patients with congenital anomalies
      necessitating surgical reconstruction are the best candidates for operation.

PMID- 9555563
TI  - Posttraumatic high-flow priapism in a 10-year-old boy: superselective
      embolization of the arteriovenous fistula.
AB  - We report on a 10-year-old boy who presented with painless priapism 11 days after
      blunt perineal trauma. Examination by color flow Doppler sonography demonstrated
      an arteriovenous fistula, which was confirmed by penile arteriography. Complete
      detumescence of the penis developed following superselective embolization with
      Ethibloc.

PMID- 9555564
TI  - Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its major
      components on basic fibroblast growth factor-induced proliferation of cultures of
      human prostate biopsies.
AB  - OBJECTIVE: To assess the effect of the lipidosterolic extract of Serenoa repens
      (LSESr) on in vitro cell proliferation in biopsies of human prostate MATERIAL AND
      METHODS: Cell proliferation was assessed by incorporation of [3H]thymidine
      followed by historadiography. RESULTS: Basic fibroblast growth factor (b-FGF)
      induced a considerable increase in human prostate cell proliferation (from +100
      to +250%); the glandular epithelium was mainly affected, minimal labeling being
      recorded in the other regions of the prostate. Similar results were observed with
      epidermal growth factor (EGF), although the increase in cell proliferation was
      not recorded in some cases. Lovastatin, an inhibitor of hydroxymethylglutaryl
      coenzyme A, antagonized both the basal proliferation and the growth factor
      stimulated proliferation of human prostate epithelium (EGF, mean inhibition
      approximately 80-95%; b-FGF, mean inhibition approximately 40-90%). Geraniol, a
      precursor of both farnesyl pyrophosphate and geranylgeranyl pyrophosphate, and
      farnesol, the precursor of farnesyl pyrophosphate, increased cell proliferation
      only in some prostate specimens, this effect being antagonized by lovastatin.
      LSESr did not affect basal prostate cell proliferation, with the exception of two
      prostate specimens in which a significant inhibition of basal proliferation was
      observed with the highest concentration of LSESr (30 micrograms/ ml). In
      contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell
      cultures; this effect was significant for the highest concentration of LSESr (30
      micrograms/ml). In some prostate samples, a similar inhibition was also noted
      with lower concentrations. Unsaturated fatty acids (UFA), in the range 1-30
      ng/ml), did not affect the basal prostate cell proliferation, only a slight
      increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10 or 30
      micrograms/ml) markedly inhibited the b-FGF-induced cell proliferation down to
      the basal value. Lupenone, hexacosanol and the unsaponified fraction of LSESr
      markedly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect
      on basal cell proliferation was noted. CONCLUSIONS: Despite the large variability
      in the response of the prostate samples to b-FGF, these results indicate that
      LSESr and its components affect the proliferative response of prostate cells to b
      FGF more than their basal proliferation.

PMID- 9555565
TI  - Urinary N-acetyl-beta-N-glucosaminidase in patients with urinary tract infection.
AB  - N-acetyl-beta-glucosaminidase (NAG, EC 3.2.1.30) is a lysosomal enzyme present in
      the proximal convoluted tubule. Increased urinary excretion of NAG has been shown
      in urinary tract infections. Our results have confirmed that urinary excretion of
      NAG is significantly higher (33.70 +/- 8.75 U/g Cr) in patients with upper
      urinary tract infection than in patients with lower urinary tract infection
      (14.10 +/- 6.80 U/g Cr) and healthy adults.

PMID- 9555566
TI  - Numerical cognition: age-related differences in the speed of executing
      biologically primary and biologically secondary processes.
AB  - Groups of younger and older adults were administered numerical and arithmetical
      tasks that varied in the extent to which they assess evolved versus culturally
      specific forms of cognition, termed biologically primary and biologically
      secondary abilities, respectively. Componential analyses of solution times
      suggested that younger adults are faster than older adults in the execution of
      biologically primary processes. For biologically secondary competencies, a
      pattern of no age-related differences or an advantage for older adults in speed
      of processing was found. The results are consistent with the view that there has
      been a cross-generational decline in arithmetical competencies in the United
      States and are discussed in terms of models of age-related change in cognitive
      performance.

PMID- 9555567
TI  - Impact of knowledge and age on tip-of-the-tongue rates.
AB  - Older (50-82), middle age (30-49), and younger (17-29) adults were asked to
      answer 57 general knowledge questions about words, objects, and people that were
      used to generate tip-of-the-tongue (TOT) experiences; none required a proper name
      answer. Middle age and older participants correctly answered more of the general
      knowledge questions and received higher scores on a vocabulary test than the
      younger participants. An analysis of variance of the number of positive TOTs
      indicated a significant main effect of age; older adults experienced more TOTs
      than younger and middle aged adults, but an analysis of covariance conducted to
      statistically control for the level of knowledge showed no significant
      differences between the age groups. Level of knowledge, and not age, contributed
      to the amount of TOTs experienced; those people with higher levels of knowledge
      experienced more TOTs. The implications of these results for the transmission
      deficit hypothesis are discussed.

PMID- 9555568
TI  - Aging and rapid aiming arm movement control.
AB  - The authors explored the motor control of target-oriented arm movements across 3
      age groups: 20 20- to 30-year-olds, 2 groups (n = 38) of older adults (54 to 64,
      and 65 to 80). Each individual completed 2 arm movement tasks that had the same
      movement difficulty but different movement directions. A mixed design was used to
      examine the differences among age groups and movement directions in reaction time
      (RT), variability in RT, movement time (MT), timing variability, and inter
      segment-interval (ISI). Comparing to the young participants, the senior adults
      initiated movement tasks slower (RT) and with more RT variability, and executed
      the arm movements slower and less consistently. The two older groups had greater
      timing variability in their movements, showed more delays (longer ISI) when
      reversing arm movement direction, and had lower correlations among segments of
      the movements than the younger group. The quality of the elderly's control of
      rapid aiming arm movements showed a regression, which suggests a lack of movement
      planning, resulting in greater use of visual feedback during movement execution.

PMID- 9555569
TI  - Serum cholesterol levels as a measure of frailty in elderly patients.
AB  - The authors evaluated the association between serum cholesterol levels and
      social, clinical, and functional characteristics in 637 elderly hospitalized
      patients (mean age = 79.1 years, range = 65-97) from the Geriatric Evaluation and
      Rehabilitation Unit (GERU) at P. Richiedei Hospital in Gussago, Brescia (Italy).
      Patients consecutively admitted to the GERU during an 18-month period underwent a
      multidimensional evaluation including information on demographics, cognitive
      status, physical health (number of chronic diseases and administered drugs),
      functional disability, and nutritional status. Mean cholesterol levels were
      significantly lower in men; persons living with others; older individuals; and
      individuals with cognitive impairment, poorer somatic health, higher disability,
      and a higher level of malnutrition. Lower serum cholesterol levels may be
      considered an independent hematologic marker of frailty in elderly hospitalized
      patients.

PMID- 9555570
TI  - Aging and scanning of imagined and perceived visual images.
AB  - The authors examined adult age differences in the proficiency of visually
      scanning across perceived and imagined displays. Participants were asked to
      indicate whether an arrow in the central region of a square grid ring pointed to
      a target square. The distance between arrow and target was varied, and all
      participants showed the expected increase in response times and error rates as
      scanning distance increased. The arrow and grid display either remained visible
      until the participant responded (perceptual condition) or disappeared after 50 ms
      (imagery condition). In both conditions, older participants required more time to
      scan and made more errors as distance increased than did younger participants.
      These findings conflict with previous studies showing that perceptual and imagery
      scanning are preserved with aging. Although methodological factors may have
      contributed to these differences, further research is needed to elucidate effects
      of aging on visual scanning.

PMID- 9555571
TI  - Memory for activities for young, young-old, and old adults.
AB  - Adult age differences in memory for activities have frequently been reported.
      However, the age range of the older sample has varied from as young as 56 to as
      old as 89. The present memory for activities study distinguished between the
      performance of young-old adults (60 to 70) and old adults (71 to 82) in
      comparison to young adults (18 to 34). Nineteen tasks were administered over a 2
      day period, and individuals were asked to recall them immediately or after a 24-h
      delay. Young-old adults' memory for activities was comparable to the young
      adults' for both immediate and delayed recall. Both the young and the young-old
      groups outperformed the old adults. The results suggest that researchers must
      consider the age of the individuals in the "old" group before drawing conclusions
      about adult age differences in memory for activities.

PMID- 9555572
TI  - Radiological and functional assessment of radiation-induced lung injury in the
      rat.
AB  - The purpose of this study is to develop an experimental model to measure
      localized radiation-induced lung injury using multiple end-points including
      breathing frequency, high-resolution computed tomography (CT), and radionuclide
      perfusion. The rats were anesthetized and the right lung irradiated with a single
      dose of 18 Gy using 200-kVp x-rays. The lung function of the animals was measured
      every 2 weeks after irradiation with the breathing rate assay. CT scanning and
      radionuclide lung perfusion assay were performed prior to and 2, 4, 10, 16, and
      34 weeks after irradiation. Significant elevation in breathing rate occurred
      after 16 weeks, with a maximal increase between 22 and 28 weeks. An increase in
      the right lung density started 4 weeks after irradiation. Regional measurements
      indicated a relatively uniform increase in density at 4 and 10 weeks, while foci
      of high-density areas were observed at the later time points. Changes in rat lung
      volume indicated shrinkage of the irradiated right lung and accompanying
      compensatory hypertrophy of the shielded left lung. Radionuclide perfusion assay
      showed significant decrease in relative blood flow in the irradiated right lung 4
      weeks after hemithoracic irradiation. Changes in breathing rate provide an index
      of overall lung function while changes in lung density, volume, and perfusion are
      of particular importance for evaluating loco-regional differences in lung
      sensitivity. This study is the first demonstration that CT can be used to measure
      volume changes after thoracic irradiation in rats.

PMID- 9555573
TI  - Effect of adrenergic stimulation on clearance from small ciliated airways in
      healthy subjects.
AB  - Mucociliary transport is an important clearance mechanism of larger airways, but
      in the smallest ciliated airways (bronchioles) it may be less effective. The
      present study aimed at investigating whether clearance from the bronchioles in
      subjects with healthy airways was stimulated by an adrenergic agonist
      (terbutaline sulphate). Tracheobronchial clearance was studied twice in 10
      healthy subjects after inhalation of 6-micron (aerodynamic diameter) monodisperse
      Teflon particles labeled with 111In. At one exposure, oral treatment with
      terbutaline sulphate, known to stimulate clearance in large airways, began
      immediately after inhalation of the particles. The other exposure was a control
      measurement. The particles were inhaled at an extremely slow flow, 0.05 L/s,
      which gave deposition mainly in the small ciliated airways (bronchioles). Lung
      retention was measured at 0, 24, 48, and 72 h. Clearance was significant every 24
      h for both exposures (p < .05, two-tailed paired t-test), with similar fractions
      of retained particles at all time points. During treatment with terbutaline
      sulphate, the subjects' pulse rates tended to be higher, but clearance rates did
      not increase. We found, as expected, no significant correlation between lung
      retention and lung function in either exposure. This study shows that an
      adrenergic agonist does not significantly influence overall clearance from the
      bronchiolar region in healthy subjects. This suggests that mucociliary transport
      does not significantly contribute to clearance from the smallest ciliated
      airways. Other mechanisms may be more important for the transportation of mucus
      from these airways.

PMID- 9555574
TI  - Regional deposition of inhaled Evans blue dye in mechanically ventilated rabbits
      with air or helium oxygen mixture.
AB  - An animal model has been used and further developed to examine and evaluate
      differences in regional deposition patterns of an Evans Blue dye (EB) tracer
      aerosol. This was done by using different carrier gas composition of either He-O2
      (80% helium, 20% oxygen) or air (79% nitrogen, 21% oxygen) in histamine-provoked
      and nonprovoked rabbits. The ratio of peripheral deposition to total deposition
      (central + peripheral), in relation to percentage increase in intratracheal
      pressure (ITP delta %), was used as an evaluation tool. The animals were
      tracheostomized, cannulated, and ventilated in a volume-controlled mode until
      they were stable. Saline or histamine was then administrated for 2 min before the
      tracer aerosol EB was given. The percentage increase in intratracheal pressure
      before and after provocation was calculated (ITP delta %) and was, on average, 51
      +/- 20% for air and 51 +/- 20% for He-O2. EB was extracted from lung tissues and
      measured with a spectrophotometer. The absorbance in different lung regions was
      used as a measure of the distribution of aerosol. Bronchial provocation gave a
      central deposition 0.55 +/- 0.11 (mean +/- SD, ratio = peripheral
      deposition/central + peripheral deposition) compared to 0.80 +/- 0.09 in the
      control group. He-O2-ventilated rabbits showed significantly higher peripheral
      deposition ratio (0.67 +/- 0.12) compared with air-ventilated rabbits (0.55 +/-
      0.11). The latter finding may be due to the difference in the degree of turbulent
      flow. There were significant correlations between intratracheal peak pressure and
      peripheral deposition, r = -.60 and r = -.71 for air and He-O2, respectively.
      This study demonstrates the possibility of using a rabbit model and different
      carrier gases for evaluation of effects of bronchial provocation.

PMID- 9555575
TI  - Modulation of rat lung Na+,K(+)-ATPase gene expression by hyperoxia.
AB  - Rats exposed to 85% O2 for 5-7 days develop tolerance to otherwise lethal
      hyperoxia (100% O2). The rate of alveolar fluid clearance increases during
      adaptation to hyperoxia, due in part to increased alveolar epithelial sodium
      channel activity. In these studies, we have investigated molecular mechanisms
      leading to increased lung Na+,K(+)-ATPase activity in hyperoxia. We exposed adult
      rats to 85% O2 (sublethal hyperoxia) for 7 days, followed by 2, 3, or 4 days in
      100% O2. Steady-state levels of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit
      mRNAs increased in whole lung tissue during hyperoxia exposures. Stability of the
      Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNA messages in whole lung RNA did
      not change significantly. Thus, lung Na+,K(+)-ATPase gene expression in sublethal
      hyperoxia appears to be regulated in part at the transcriptional level. Alveolar
      epithelial type II (ATII) cell Na+,K(+)-ATPase alpha 1 and beta 1 subunit
      proteins, measured by quantitative immunofluorescence, increased significantly
      after sublethal hyperoxia and 100% O2 exposures. Increases in lung fluid
      clearance after sublethal hyperoxia are associated with increased ATII cell
      Na+,K(+)-ATPase protein and whole lung Na+,K(+)-ATPase mRNA expression, which
      correspond to previously described increases in epithelial sodium channel
      expression under these conditions.

PMID- 9555576
TI  - Inflammatory and epithelial responses in mouse strains that differ in sensitivity
      to hyperoxic injury.
AB  - The pulmonary response to various toxicants including bleomycin, ozone, ionizing
      radiation, and hyperoxia is highly variable among mouse strains. The current
      study tests the hypothesis that at a similar stage of injury, regardless of
      strain, expression of inflammatory cytokine and epithelial marker genes would be
      similar, indicating a common pathway of injury progression. Three strains of
      mice, C57B1/6J, 129/J, and C3H/HeJ, ranging from sensitive to resistant, were
      exposed to > 95% O2 for varying times. Ribonuclease protection was used to
      quantify changes in cytokine mRNA. Despite differences in the kinetics, each
      strain demonstrated similar hyperoxia-induced changes in the abundance of
      interleukin (IL)-6, IL-1 beta, IL-3, and tumor neucrosis factor (TNF)-alpha. For
      each strain, death was accompanied by similar increases in cytokine mRNAs above
      steady-state control levels. Other inflammatory cytokines, including IL-1 alpha,
      IL-4, and interferon (IFN)-gamma, were unaltered in all strains at all times. In
      situ hybridization analysis of the epithelial markers, surfactant protein B
      (SPB), and clara cell secretory protein (CCSP) at the time of proinflammatory
      induction showed a similar pattern of expression in all strains. Increased SPB
      was detected in bronchiolar epithelium, while the number of type II cells
      expressing this message declined. Both the number of cells expressing CCSP as
      well as abundance per cell declined. These results suggest that although
      differences in acute sensitivity to hyperoxia exist between mouse strains, once
      initiated, acute epithelial cell injury and associated inflammatory changes
      follow the same pattern in all strains.

PMID- 9555577
TI  - Expression of the insulin-like growth factor system in postpneumonectomy lung
      growth.
AB  - The insulin-like growth factors (IGF-I and IGF-II) may play an important role in
      postpneumonectomy compensatory lung growth by translating hormonal inputs and
      mechanical forces into cellular proliferation signals. We examined the mRNA
      abundance of IGF-I, IGF-II, and IGF binding proteins (IGFBPs) in lungs of rats on
      postoperative days 1, 2, 3, 5, and 7 following left pneumonectomy (PNX) or
      shamoperation (SC) and in normal animals (CON). There was no difference in the
      abundance of lung IGF-I mRNA (measured by Northern analysis) or serum IGF-I
      (measured by radioimmunoassay (RIA)) between SC and PNX animals. IGF-II mRNA
      abundance was initially decreased following PNX (73% decrease compared to SC
      animals on day 1, p < .05) and then rose to approach SC group values on
      subsequent days. Transcripts for IGFBP-2, -3, -4, -5, and -6 were decreased in
      both the SC and PNX groups compared to CON animals on the day following
      pneumonectomy, then rose back to baseline by postoperative day 2-3. Tissue
      IGFBPs, measured by ligand blot analyses, were not different in either the SC or
      PNX groups. In contrast, all serum IGFBP bands were increased on postoperative
      day 1 following either sham or PNX surgery. In addition, serum IGFBP-4 was
      increased in PNX animals compared to the SC group on days 1 and 2 (increase of
      38% and 78%, respectively, p < .05). We conclude that the changes observed in
      lung IGF and IGFBP expression following pneumonectomy do not represent major.

PMID- 9555578
TI  - Depletion of iron and ascorbate in rodents diminishes lung injury after silica.
AB  - Exposures of the lung to iron chelates can be associated with an injury. The
      catalysis of oxygen-based free radicals is postulated to participate in this
      injury. Such oxidant generation by mineral oxide particles can be dependent on
      availability of both iron and a reductant. We tested the study hypothesis that
      lung injury after silica is associated with the availability of both iron and
      ascorbate in the host by depleting this metal and reductant in the lungs of rats
      and guinea pigs, respectively. Rats were fed either a normal diet or a diet
      deficient of iron. After 30 days, animals were instilled with either saline or
      1.0 mg Minusil-5 silica. Relative to saline, silica significantly increased
      neutrophils and lavage protein. Iron depletion significantly diminished both the
      cellular influx and injury but only at 1 week after silica exposure. Guinea pigs
      were provided either a normal diet supplemented with 1,000 ppm vitamin C or a
      diet deficient in ascorbate. After 14 days, the guinea pigs were instilled with
      either saline or 1.0 mg silica. Silica exposure significantly increased
      neutrophils and lavage protein. Ascorbate depletion significantly diminished the
      influx of inflammatory cells and injury at both 1 day and 1 week after silica
      exposure. We conclude that host concentrations of both iron and ascorbate can
      affect lung injury after silica exposure.

PMID- 9555580
TI  - Strong variable clinical presentation in 3 patients with 7q terminal deletion.
AB  - We report 3 patients with a 7q terminal deletion. The first, a 7 weeks old
      female, with a de novo 7q36-->qter deletion, was microcephalic and had a partial
      hypoplasia of the corpus callosum on the MRI-scan of the brain. The second, a 3
      months old male, showed microcephaly, disproportionate growth retardation,
      truncal obesity and facial dysmorfism giving the clinical impression of a
      "microcephalic primordial dwarfism (osteodysplastic type)". At the age of 6
      months he had developed a single maxillary central incisor suggesting a minimal
      form of holoprosencephaly (HPE). Additional FISH-studies showed a 7q36.1-->qter
      deletion, as the unbalanced product of a t(5;7)(q35.2;q36.1)pat. The de novo 7q36
      ->qter deletion in the third patient, a 5 years old female, was associated with
      borderline intelligence, mild microcephaly, small midface, choanal narrowing and
      a single maxillary central incisor as a minimal form of HPE. CT- and MRI-scan of
      the brain were normal. In these 3 patients extensive FISH analysis was performed
      to investigate the possible involvement of the HPE gene region on chromosome
      7q36. The target gene for HPE, the Sonic hedgehog gene (SHH) as well as several
      other genes important for normal brain development (En2;HOX1,HTR5A) were found to
      be deleted in all three patients. Our findings stress the importance of 7q36
      microdeletion studies in patients with even minimal signs of HPE, as relative
      microcephaly with small midface (choanal narrowing), agenesis/hypoplasia of the
      corpus callosum/septum pellucidum, thalamic fusion or a single maxillary central
      incisor.

PMID- 9555581
TI  - Neonatal death in Marshall-Smith syndrome.
AB  - Marshall-Smith syndrome is characterized by accelerated skeletal maturation,
      failure to thrive and dysmorphic features. Since 1971, twenty cases of MSS have
      been reported. We describe another patient with a very early death demonstrating
      the clinical variability of the syndrome and the importance of systematic X rays
      of the skeleton for determining the causes of fetal or neonatal death.

PMID- 9555582
TI  - Congenital camptodactyly associated with the 48,XXYY syndrome.
AB  - A male premature infant presented with slow development and congenital
      camptodactyly of both hands. Chromosome analysis showed a 48,XXYY karyotype. As
      far as we know, this is the first report describing congenital camptodactyly
      associated with the 48,XXYY syndrome.

PMID- 9555583
TI  - Symbrachydactyly involving hands and feet.
AB  - Two patients are described with a symbrachydactyly of the hand and foot. This is
      a rare combination which cannot be explained by the subclavian artery supply
      disruption sequence.

PMID- 9555584
TI  - Oligodontia, microcephaly and facial dysmorphia syndrome.
AB  - Congenital absence of third molars is common. However absence of the other
      permanent teeth is relatively rare. Absence of teeth may be isolated or
      associated to other features. We had the opportunity to examine a girl with
      oligodontia associated to microcephaly, to facial dysmorphia and to short
      stature.

PMID- 9555585
TI  - Lymphedema combined with brachydactyly and tachycardia.
AB  - Hereditary lymphedema can appear at birth or later up to adulthood. It may be
      seen in connection with diverse symptoms forming various syndromes. The authors
      report a family with hereditary lymphedema, brachydactyly, syndactyly and
      tachycardia. Lymphedema and tachycardia could appear together by chance. However
      this combination could also be a syndrome.

PMID- 9555586
TI  - Oral-facial-digital syndrome type IV (Mohr-Majewski syndrome): a fetopathological
      study.
AB  - We present a 22-week male fetus with cleft lip and palate, lobulated tongue,
      talipes equinovarus, and polysyndactyly. In addition there was skeletal dysplasia
      with micromelia and short ribs. Autopsy revealed a cardiac anomaly
      (perimembranous VSD), very incomplete lobation of the lungs, mild congenital
      hepatic fibrosis, and segmental renal cystic dysplasia. Brain anomalies included
      internal hydrocephalus, olfactory aplasia, and agenesis of the corpus callosum.
      This constellation of multiple congenital anomalies is consistent with the oral
      facial-digital syndrome (OFDS) type IV. OFDS type IV may be a heterogeneous
      condition. Our pathological findings confirm that at least some of these cases a
      transitional phenotype between OFDS type II (Mohr syndrome) and short rib
      polydactyly syndrome type II (Majewski syndrome).

PMID- 9555587
TI  - Diaphragmatic hernia in the Coffin-Siris syndrome.
AB  - At 32 weeks of gestation, delivery of a female fetus was induced because of
      severe malformations seen on ultrasonogram: congenital diaphragmatic hernia and
      cerebellar hypoplasia. The diagnosis of Coffin-Siris syndrome was based on the
      physical examination: coarse face with low-set ears, low nuchal hairline, scalp
      hypotrichosis and hypoplasia of the nails of fingers and toes with absence of the
      right fifth fingernail. Autopsy confirmed the prenatally diagnosed major
      associated abnormalities: hypoplasia of the cerebellum and congenital
      diaphragmatic hernia. Various clinical entities are included in the differential
      diagnosis.

PMID- 9555588
TI  - Distinct familial syndrome of severe to profound mental retardation, spastic
      paraplegia with contrasting axial hypotonia, short stature and distinct
      craniofacial appearance with nasal hypoplasia.

PMID- 9555589
TI  - Brachydactyly and fragile site at 16q22: a chance association.

PMID- 9555590
TI  - Hypoplastic claviculae in the Kabuki (Niikawa-Kuroki) syndrome.

PMID- 9555591
TI  - Trisomy 21 in a second trimester male hydropic fetus with "Noonan-syndrome
      phenotype": nuchal and thoracic lymphangiomatosis, oedema of the dorsum of hands
      and feet, and bicuspid pulmonary valve.

PMID- 9555592
TI  - A lethal, unclassifiable form of micromelic dwarfism with posterior cleft palate,
      multiple cervicothoracal vertebral anomalies and iliac hypoplasia: evidence for
      autosomal recessive inheritance.

PMID- 9555593
TI  - Preaxial polydactyly in the 4p- syndrome.

PMID- 9555594
TI  - Clozapine and fluvoxamine, a curious complexity.

PMID- 9555595
TI  - Therapeutic equivalence of risperidone given once daily and twice daily in
      patients with schizophrenia. The Risperidone Study Group.
AB  - A study was conducted to determine whether once-daily administration of
      risperidone was as effective and safe as twice-daily administration. In a double
      blind 6-week trial, 211 patients with acute exacerbation according to DSM-III-R
      criteria were randomly assigned to receive risperidone at 8 mg once daily or 4 mg
      twice daily. The primary efficacy measure was the treatment response rate,
      defined as a 20% or greater reduction in total Positive and Negative Syndrome
      Scale (PANSS) scores. Severity of extrapyramidal symptoms was assessed by the
      Extrapyramidal Symptom Rating Scale. The percentage of patients who showed a
      treatment response at endpoint was not significantly different between groups
      (76%, once-daily; 72%, twice-daily), nor was the median time to first treatment
      response (14 days, both groups). Significant reductions in PANSS total and
      subscale scores and PANSS-derived Brief Psychiatric Rating Scale were observed in
      both groups, with no significant between-group differences. Extrapyramidal
      Symptom Rating Scale scores did not differ significantly between groups. There
      were no clinically relevant changes in vital signs, electrocardiograms, or
      clinical laboratory test results in either group. Gradual dosage titration over
      the first 3 days of treatment was well-tolerated in both groups. The median
      trough plasma concentrations of risperidone, 9-hydroxyrisperidone, and
      risperidone plus 9-hydroxyrisperidone were significantly lower with once-daily
      than with twice-daily administration; median plasma concentrations measured
      within the first 8 hours after administration tended to be higher with once-daily
      administration. These differences did not affect the safety and efficacy of
      risperidone. Risperidone given once daily at 8 mg is as effective as twice-daily
      administration of 4 mg in the treatment of acute exacerbations of schizophrenia.
      Both regimens were equally well-tolerated.

PMID- 9555597
TI  - A controlled trial of ondansetron, a 5-HT3 antagonist, in benzodiazepine
      discontinuation.
AB  - Serotonin is implicated in the etiology of anxiety disorders and in the
      anxiolytic actions of benzodiazepines. Preclinical studies with 5-HT3 receptor
      antagonists, including ondansetron, show they have anxiolytic properties and that
      ondansetron suppresses withdrawal anxiety after abrupt discontinuation of chronic
      benzodiazepine treatment. We evaluated the efficacy of ondansetron as an
      adjunctive medication in the discontinuation of benzodiazepines in long-term
      users. One hundred eight patients who had used alprazolam or lorazepam regularly
      for > 3 months entered, and 97 completed a randomized double-blind
      discontinuation treatment program during which they received either ondansetron 2
      mg twice daily or placebo and flexibly tapered their benzodiazepine over a 6-week
      period. There were no significant differences between the patients who had
      entered and completed treatment. Three weeks postmedication, 63% of the patients
      discontinued use of benzodiazepine. The percentage of reduction of benzodiazepine
      daily dosage at all time points in the treatment trial was similar for the
      ondansetron and placebo groups. Ondansetron had no significant effects on
      severity of withdrawal symptoms or levels of anxiety. High placebo response may
      have prevented detection of an ondansetron effect. At 1 year follow-up, 68% of
      patients reported that they stopped using benzodiazepine. Patient characteristics
      were more important than ondansetron in tapered benzodiazepine discontinuation.

PMID- 9555596
TI  - Risperidone versus haloperidol and amitriptyline in the treatment of patients
      with a combined psychotic and depressive syndrome.
AB  - In a multicenter, double-blind, parallel group trial, the efficacy of risperidone
      (RIS) was compared with a combination of haloperidol and amitriptyline (HAL/AMI)
      over 6 weeks in patients with coexisting psychotic and depressive symptoms with
      either a schizoaffective disorder, depressive type, a major depression with
      psychotic features, or a nonresidual schizophrenia with major depressive symptoms
      according to DSM-III-R criteria. A total of 123 patients (62 RIS; 61 HAL/AMI)
      were included; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL
      combined with 180 mg AMI. Efficacy results for those 98 patients (47 RIS; 51
      HAL/AMI) who completed at least 3 weeks of double-blind treatment revealed in
      both treatment groups large reductions in the Positive and Negative Syndrome
      Scale-derived Brief Psychiatric Rating Scale (RIS 37%; HAL/AMI 51%) and the Bech
      Rafaelsen Melancholia Scale total scores (RIS 51%; HAL/AMI 70%). The reductions
      in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale
      scores in the total group were significantly larger in the HAL/AMI group than in
      the RIS group (p < 0.01), mostly because of significant differences in the
      subgroup of patients suffering from depression with psychotic features, whereas
      treatment differences in the other diagnostic subgroups were not significant. The
      incidence of extrapyramidal side effects as assessed by the Extrapyramidal
      Symptom Rating Scale was slightly higher under RIS (37%) than under HAL/AMI
      (31%). Adverse events were reported by 66% of RIS and 75% of HAL/AMI patients.
      The results of this trial suggest that the therapeutic effect of HAL/AMI is
      superior to RIS in the total group of patients with combined psychotic and
      depressive symptoms. However, subgroup differences have to be considered.

PMID- 9555598
TI  - Imipramine in the treatment of social phobia.
AB  - We report the results of an 8-week open trial of imipramine in 15 patients with
      social phobia. Nine patients completed the trial; six dropped out early because
      of adverse effects. The mean reduction in the Liebowitz Social Anxiety Scale was
      15% and 18% for the intent-to-treat and completer groups, respectively; the
      overall response rate (based on the Clinical Global Impression Scale of 1 or 2,
      very much or much improved) was 20% (3/15) and 22% (2/9), respectively. The
      results from this open trial do not support the efficacy of imipramine as a
      treatment for social phobia.

PMID- 9555599
TI  - A meta-analysis of the effects of venlafaxine on anxiety associated with
      depression.
AB  - Venlafaxine is the first member of a novel class of antidepressants that inhibits
      the reuptake of both serotonin and norepinephrine. Clinical trials of venlafaxine
      have demonstrated its efficacy and safety in the treatment of patients diagnosed
      with major depression. Because patients who have depression also often have
      anxiety, recent investigations have focused on determining whether venlafaxine
      can relieve symptoms of anxiety in depressed patients. We performed a pooled
      analysis of six short-term trials of venlafaxine, retrospectively measuring
      anxiety in anxious depressed patients using the Hamilton Rating Scale for
      Depression (HAM-D), Anxiety/Somatization factor and Anxiety Psychic item scores.
      Three studies were placebo-controlled, and three were placebo- and active-drug
      controlled; active controls were imipramine in two trials and trazodone in the
      third trial. Patients were categorized as having anxiety accompanying depression
      if baseline HAM-D Anxiety Psychic item scores were 2 or greater. Anxious
      depressed patients treated with venlafaxine showed greater improvement than those
      treated with placebo beginning at week 3, according to the HAM-D
      Anxiety/Somatization factor score, and beginning at week 1, according to the
      Anxiety Psychic item score. Both effects were maintained at week 6 of treatment
      (and at week 12 in the one study of longer duration). Finally, treatment with
      venlafaxine resulted in a highly significant (p < or = 0.001) improvement in
      depression scores in patients who were anxious at baseline, compared with placebo
      treated patients. The results of this analysis demonstrate that venlafaxine is
      more effective than placebo in reducing symptoms of anxiety in depressed patients
      and suggest that venlafaxine may afford a monotherapy option for treating
      patients who have a comorbid diagnosis of depression with anxiety.

PMID- 9555600
TI  - Benzodiazepine-receptor ligands in humans: acute performance-impairing, subject
      rated and observer-rated effects.
AB  - The study presented here compared the acute performance-impairing, subject-rated,
      and observer-rated effects of quazepam (15, 30, and 45 mg), triazolam (0.1875,
      0.375, and 0.5625 mg), zolpidem (7.5, 15, and 22.5 mg), and placebo in nine
      healthy, non-drug-abusing humans. Quazepam, a trifluoroethylbenzodiazepine, was
      chosen for study because, when compared with triazolam, a triazolobenzodiazepine,
      it is a relatively weak benzodiazepine-receptor ligand, and it may bind
      selectively to the BZ1 benzodiazepine-receptor subtype. Zolpidem, an
      imidazopyridine, is the most commonly prescribed hypnotic and was chosen for
      study because it is biochemically distinct from benzodiazepine hypnotics and also
      purportedly binds selectively to the BZ1 benzodiazepine-receptor subtype.
      Triazolam was chosen as the reference compound because it binds nonselectively to
      BZ1 and BZ2 benzodiazepine-receptor subtypes. Triazolam, zolpidem, quazepam, and
      placebo were administered orally in a double-blind, crossover design. Triazolam
      and zolpidem produced orderly dose- and time-related impairment of learning,
      performance, and recall, and produced sedative-like subject- and observer-rated
      drug effects. The behavioral pharmacologic profile of zolpidem and triazolam was
      indistinguishable in that at peak effect, the absolute magnitude of drug effect
      was comparable across the various measures. Quazepam, by contrast, did not impair
      performance on any task to a statistically significant degree, nor did it produce
      significant sedation as measured by subject- and observer-rated drug-effect
      questionnaires. Whether these effects are a result of the unique benzodiazepine
      receptor binding profile of quazepam or the testing of insufficient dosages is
      unknown. Future research could extend the findings presented here by testing
      higher dosages of quazepam.

PMID- 9555602
TI  - Clozapine induced atrial fibrillation.

PMID- 9555601
TI  - Serum levels of valproate and carbamazepine in breastfeeding mother-infant pairs.
AB  - Few data are available about the use of anti-convulsants during breastfeeding. In
      this article, three women with bipolar disorder who insisted upon breastfeeding
      their infants were studied. One mother was treated with carbamazepine (CBZ) and
      two were treated with valproate (VLP) monotherapy. Mother and infant serum levels
      were assessed when maternal steady-state was reached. The infant whose mother
      took CBZ developed a serum level that was 15% of the total maternal CBZ. Free CBZ
      was 20% of maternal values. The two infants whose mothers took VLP developed low
      serum levels (1.5 and 6.0% of maternal values). In the series, the serum levels
      of both CBZ and VLP were lower than previously reported values. However,
      information is limited and careful monitoring is recommended.

PMID- 9555603
TI  - Delirium in elderly patients treated with risperidone: a report of three cases.

PMID- 9555604
TI  - Treatment of refractory rapid cycling bipolar disorder with risperidone.

PMID- 9555605
TI  - Comments on article by Tran and colleagues, "Double-blind comparison of
      olanzapine versus risperidone in treatment of schizophrenia and other psychotic
      disorders".

PMID- 9555606
TI  - Comments on article by Tran and associates, "Double-blind comparison of
      olanzapine versus risperidone in treatment of schizophrenia and other psychotic
      disorders".

PMID- 9555608
TI  - Treatment-resistant schizophrenia: the importance of early detection and
      treatment. Introduction.

PMID- 9555607
TI  - ApoE-epsilon 4 allele and susceptibility to drug-induced memory impairment in the
      elderly.

PMID- 9555609
TI  - Predictors of outcome in schizophrenia.
AB  - Several factors have been reported to be associated with poor outcome in
      psychosis. A prospective study was conducted to identify and subsequently assess
      the relative prognostic value of factors that might assist in the earlier
      identification of patients likely to have a poor outcome. The results confirmed
      that certain factors, including male gender, family history of schizophrenia,
      structural brain abnormalities, absence of adverse life events, and tardive
      dyskinesia, were indeed associated with poor outcome.

PMID- 9555610
TI  - The evolution of treatment resistance: biologic implications.
AB  - The evolution of resistance of positive symptoms to antipsychotic therapy may
      represent a valuable means of subtyping schizophrenia. In contrast, resistance of
      negative symptoms and cognitive function to antipsychotic agents seems to be
      present from the first episode of psychotic symptoms and does not evolve over
      time to the same extent. If these findings are validated, this clearly points
      toward differences in the etiology of these components of schizophrenia. Data
      from a cohort of 223 patients with unsatisfactory responses to classical
      antipsychotic therapy are evaluated, at least 60% of whom responded to subsequent
      treatment with clozapine. Comparisons were made between the subgroups of patients
      with primary and delayed onset treatment resistance. Both subgroups responded to
      clozapine therapy, although better response was evident for patients with delayed
      resistance. The withdrawal of clozapine from patients who had previously been
      responsive to classical antipsychotic therapy was capable of inducing treatment
      resistance.

PMID- 9555611
TI  - The cognitive efficacy of atypical antipsychotics in schizophrenia.
AB  - Cognitive dysfunction, a symptom of schizophrenia, has been recently identified
      as an important measure of outcome in the treatment of this disorder. Drug
      mediated symptom improvement, the traditional measure of treatment success for
      schizophrenia, typically fails to associate with modifications of cognitive
      dysfunction, resulting in a failure of the patient to reintegrate into society. A
      paradigm shift is now required in the conceptualization of treatment success away
      from symptom decrement and towards treatments that improve cognitive function.
      Clozapine treatment has been shown to provide a significantly greater improvement
      in several domains of cognitive function, especially attention and verbal
      fluency, compared with conventional neuroleptics, whereas risperidone appears to
      have a beneficial effect on working memory. These results may be because of the
      normalization of dopamine function by clozapine and antagonism of 5HT2 receptors.

PMID- 9555612
TI  - The development of treatment resistance in patients with schizophrenia: a
      clinical and pathophysiologic perspective.
AB  - The pathophysiologic process and clinical factors that contribute to the
      development of treatment resistance in schizophrenia are not well defined. This
      article describes data indicating that treatment resistance may evolve over the
      course of the patients' illness and maturational development. Data from
      multiepisode patients suggest that early effective intervention with clozapine
      can prevent treatment resistance. Early identification of patients with signs of
      treatment resistance is vital. Treatments must be effective and prevent relapse.
      At the first indication that a patient may be developing resistance (e.g., the
      emergence of extrapyramidal symptoms or increases in negative symptomatology) or
      may not be complying with treatment, clozapine therapy should be considered.

PMID- 9555613
TI  - Association between pollen hypersensitivity and edible vegetable allergy: a
      review.
AB  - Over the last three decades several authors have described the existence of an
      association between sensitivity to different pollens and sensitivity to diverse
      edible vegetables. An association between ragweed pollinosis and hypersensitivity
      to Cucurbitaceae vegetables (e.g., watermelon, melon, cucumber) and banana has
      been reported. Other authors have found a relationship between birch pollinosis
      and sensitization to hazelnut, apple, carrot, potato, kiwi and other vegetables.
      Additionally, several papers have shown the association between mugwort
      pollinosis and sensitization to celery, carrot, spices, nuts, mustard and
      Leguminoseae vegetables. Later, some studies showed association between grass
      pollinosis and sensitization to tomato, potato, green- pea, peanut, watermelon,
      melon, apple, orange and kiwi. Finally, an association between sensitization to
      plantain pollen and melon hypersensitivity was also described. The association
      between pollinosis and edible vegetable sensitization has been explained by the
      combination of different hypotheses, such as the following: 1) presence of
      lectins in edible vegetables; 2) existence of IgE to carbohydrates of the
      glycoproteins (cross-reactive carbohydrate determinants); and, 3) existence of
      common allergens between pollens and edible vegetables. Up to now three allergens
      have been identified as responsible for cross-reactivity in these associations:
      profilin, a 14 kd protein that regulates actin; Bet v 1, the 18 kd birch pollen
      allergen; and a 60-69 kd allergen. It is important to study in depth these
      associated sensitizations and the common allergens responsible for them in order
      to improve diagnostic methods and treatment of these syndromes.

PMID- 9555614
TI  - Study of IgE-dependent sulphidoleukotriene cellular releasability.
AB  - Cellular releasability of mediators, as termed by Lichtenstein and Conroy (1),
      can be triggered by interaction with allergens, anti-IgE antibodies or other
      agonists. Genetic factors can also influence the cell releasability. We studied
      104 subjects, including 92 atopic patients (62 sensitive to D. pteronyssinus and
      54 sensitive to Lolium perenne) and 12 healthy controls. Sulphidoleukotriene
      (sLT) production was measured after allergen and anti-IgE stimulus with CAST
      ELISA, and histamine release using a fluorometric method. We found a significant
      sLT production after anti-IgE stimulation, higher than in basal conditions with
      medium alone. The sLT production was also significantly higher in sensitive
      patients than in healthy controls. We found 14.5% of healthy and atopic subjects
      to be non-responders to anti-IgE stimulus. We also found a positive and
      significant correlation between sLT production and histamine release. Moreover,
      we observed a significant positive correlation between IgE-dependent and antigen
      specific sLT release. We also noticed a decrease in sLT production and a decrease
      in histamine release with aging. Male patients had a sLT production significantly
      higher than female patients. With respect to clinical diagnosis, the group of
      patients with rhinitis had the highest mediator production. Finally, pollinic
      patients studied during the spring had a higher sLT production to anti-IgE than
      those studied out of this season. We conclude that quantification of sLT
      production after anti-IgE stimulation is a useful method to study cell
      releasability of mediators and that such releasability is higher in atopic
      patients than in healthy donors. We must emphasize the usefulness in allergy
      diagnosis of relying not only on the use of methods demonstrating the existence
      of sensitization to an allergen, but also of techniques able to quantify the
      ability to respond to that allergen. In this way we would be able to evaluate the
      clinical and immunological evolution of patients and to follow up the efficacy of
      their treatment.

PMID- 9555615
TI  - Cetirizine reduces conjunctival nonspecific hyperreactivity in children with mite
      allergy.
AB  - As mite allergy is characterized by a continuous allergen exposure, persistent
      inflammation is always detectable even during symptomless periods. It has been
      reported that mite allergic patients present a nonspecific hyperreactivity to
      different stimuli, including hyperosmolar solution. Since it has been reported
      previously that cetirizine is able to reduce minimal persistent inflammation due
      to mite allergy, the aim of the study was to investigate the effect of cetirizine
      on nonspecific conjunctival hyperreactivity. Twenty children with mite allergy
      were studied; two hyperosmolar conjunctival challenges were performed before and
      after cetirizine or placebo treatment, lasting one week. Patients treated with
      cetirizine showed a significant reduction in nonspecific conjunctival
      hyperreactivity compared to the placebo group (p < 0.05). In conclusion,
      cetirizine was able to reduce nonspecific hyperreactivity related to allergic
      inflammation.

PMID- 9555616
TI  - Serial determinations of Der p 1 and Der f 1 show predominance of one
      Dermatophagoides species.
AB  - One dust sample each month was collected for an average of 11 months throughout
      the year from the bedroom carpet of 39 mite allergic, asthmatic individuals
      living in the Tampa Bay area of Florida. Dust samples were collected from a
      square meter area from the bedroom carpet for 2 min using a portable vacuum
      cleaner and analyzed using two-site monoclonal antibody assays. The geometric
      mean of Dermatophagoides allergens Der p 1 and Der f 1 levels measured in each
      individual home was used in the statistical analysis of the results and reflects
      the average allergen level per year per home. Der p 1 levels were greater than
      Der f 1 in 21 homes; five homes had between 1.1 and 5 times more; one home had
      between 5 and 10; and 15 had between 10 and 175. Der f 1 levels were greater than
      Der p 1 in 18 homes; seven homes had between 1.1 and 5 times more; four had
      between 5 and 10; and seven homes had between 10 and 44. Spearman rank analysis
      of the results yielded a negative correlation coefficient (Rho) = -0.213 (p =
      0.19) between Der p 1 and Der f 1 levels. These data suggest that when mite
      allergen levels reach a geometric mean value of approximately 2 micrograms/gram
      of dust throughout a year, one mite species predominates over the other.

PMID- 9555618
TI  - Late onset asthma clinical and immunological data: importance of allergy.
AB  - In people over 65 years of age (mean age 72) late onset asthma (LOA) is often
      mistaken for chronic obstructive pulmonary disease (COPD). Furthermore, it is
      generally believed that true allergic asthma starts very seldom in old age and
      that, in this case, it is actually intrinsic asthma i.e., without any
      sensitization to aeroallergens. The aim of this study was to show that LOA is not
      an uncommon entity and is often allergic. Among a population of 1,888 subjects
      (over 65 years of age) in a general medicine ward we found 21 patients (1.1%)
      corresponding to this entity. The diagnosis of asthma was assessed according to
      clinical data, pulmonary function and nasal provocation tests, and blood
      eosinophilia. The diagnosis of atopy was assessed on total IgE, prick tests and
      RAST for the commonest allergens of our area. This group of 21 patients was
      compared to three groups of age-matched subjects including: 68 patients afflicted
      with chronic bronchitis, a group of 14 patients who had asthma before the age of
      65 (presenile asthma), and 20 normal controls. A group of 15 asthmatics under age
      65 was also included (young asthma mean age 37). We found a rather high incidence
      of allergy (72%), mostly to Dermatophagoides pteronyssinus, but also to the
      pollens Parietaria judaica, grasses and Olea europea. Although the average age
      (except in the young asthma group) and the severity of symptoms were the same in
      the four groups, unexpectedly mean RAST and skin test values were higher in LOA
      than in the two groups of young asthmatics and presenile asthmatics. It was
      concluded that LOA is not uncommon among elderly patients over 65, which is in
      contrast with most previous studies; 72% of our cases were allergic, the main
      allergens being mite, and Parietaria judaica pollen.

PMID- 9555617
TI  - Is it useful to add an anticholinergic treatment to beta 2-adrenergic medication
      in acute asthma attack?
AB  - The aim of our study was to determine whether the combination of an
      anticholinergic treatment with a beta 2-adrenergic medication is a more effective
      treatment for acute asthma attack than the two treatments individually. The
      association of salbutamol-ipratropium was compared to treatment with salbutamol
      and ipratropium alone. It was a prospective double-blind study in children with
      acute asthma attack, participating as outpatients. Their clinical history and
      characteristics of bronchial obstruction were recorded on a standard form.
      Afterwards, they were included in one of the three following study groups: group
      one, 100 micrograms/inh salbutamol; group two, 20 micrograms/inh ipratropium;
      group three, 100 micrograms/inh of salbutamol plus 20 micrograms/inh ipratropium.
      There were 40 patients in each group, with Tal score +/- 5 and PEF < 80% of the
      predicted value. They were evaluated at the beginning (0 min), and at 15, 30, 45,
      60, 80, 100 and 120 min. Each patient was treated with two inhalations of the
      study medication and was then evaluated for variations in Tal score. The mean age
      was 7.3 years; Tal score was 5.6, 5.6 and 6.0 at 0 min (p > 0.05). Decrease in
      Tal score after 15 min meant p < 0.01 for salbutamol-ipratropium and salbutamol
      vs. ipratropium. At 30 min p < 0.05 for salbutamol-ipratropium vs. salbutamol,
      and at 45 min p < 0.01 for salbutamol-ipratropium vs. salbutamol. PEF at 0 min
      was 70.9%, 71.3% and 68.6% (p > 0.05) increasing after 15 min. At 30 min p < 0.05
      for salbutamol-ipratropium vs. salbutamol, and p < 0.01 vs. ipratropium. At 45
      min p < 0.01 for salbutamol-ipratropium vs. salbutamol and ipratropium. A total
      4.7 doses of salbutamol were needed to improve the asthma attack, 5.3 of
      ipratropium and 3.7 of salbutamol-ipratropium, with p < 0.01 for salbutamol
      ipratropium vs. salbutamol and ipratropium. We conclude that the combination of
      salbutamol and ipratropium is more effective than each medication alone in
      treating acute asthma attacks in pediatric patients.

PMID- 9555619
TI  - Different responses of lymphocyte to human placenta conditioned medium in vitro.
AB  - Several cytokines appear to be implicated in peri-implantation events and in
      maternal-fetal interaction. The majority of these molecules appear in
      supernatants or in extracts of placental origin. The purpose of this study was to
      investigate the action of human placenta conditioned medium (HPCM) on peripheral
      lymphocytes in vitro. Peripheral lymphocytes of women with different numbers of
      deliveries, of nulliparous and pregnant women, as well as of men, were cultivated
      in their own plasma with and without HPCM at 5%, 10% and 20%. The index of
      lymphocyte blast transformation (ILBT) was determined (values of > or = 0.5
      indicated stimulation). In women who had had children, the highest lymphocyte
      blastogenesis was observed with HPCM at 10%, this finding being correlated to the
      numbers of deliveries (r = 0.828). In pregnant women, even though the highest
      answer was also obtained with HPCM at 10%, the addition of suboptimal
      concentration of HPCM (5%) produced blastic transformation (IBLT: x = 0.54 +/-
      0.05), which was not observed in women who had had children. Lymphocytes of men
      and nulliparous women did not respond to any of the HPCM concentrations tested.
      In conclusion, HPCM at 10% was still the best concentration to produce lymphocyte
      blastogenesis. In addition, in the plasma of pregnant women, there may be some
      substance that enhanced the action in vitro of the extract, thus permitting
      threshold reduction necessary for lymphocyte stimulation.

PMID- 9555620
TI  - Honeybee venom specific IgG subclass antibodies in Brazilian beekeepers and in
      patients allergic to bee stings.
AB  - Fifty-nine beekeepers who had been practicing apiculture for more than 2 years
      were selected in order to determine the distribution of bee venom specific IgG
      subclasses using ELISA. The assays were standardized into arbitrary units. For
      comparison, IgG subclasses were determined in eight individuals allergic to bee
      stings who did not receive specific treatment. No correlation was detected
      between beekeeping time and specific IgG1, IgG2 or IgG4 levels. There was a
      correlation between IgG2 levels and mean number of stings per month received by
      the beekeepers. Twenty-five percent of the beekeepers presented bee venom
      specific IgE class II or more in an ELISA assay. The IgG1 levels detected in
      beekeepers were similar to those detected in allergic individuals. IgG2 and IgG4
      levels were significantly higher in beekeepers than in allergic individuals. IgG3
      was not detected in any group studied. In conclusion, the maintenance of high
      levels of bee venom specific IgG2 and IgG4 represents a characteristic of
      beekeepers. These subclasses may be related to a modulatory effect of IgG on
      allergic reactions.

PMID- 9555621
TI  - Severe allergic conjunctivitis and chemosis caused by disodium cromoglycate.
AB  - A 63-year-old man with chronic, nonallergic rhinoconjunctivitis presented
      immediate adverse reactions, such as intense itching, burning, redness and severe
      swelling of both conjunctivae after using disodium cromoglycate eye drops. Skin
      prick tests and conjunctival provocation tests were positive with pure disodium
      cromoglycate. Circulating IgE-specific antibodies to disodium cromoglycate in
      serum were demonstrated by RAST. We suggest that the acute ocular reaction was
      caused by disodium cromoglycate and that the underlying mechanism was probably an
      IgE-mediated immunological reaction.

PMID- 9555623
TI  - A support system for content-based medical image retrieval in object oriented
      databases.
AB  - This work describes both the concepts used in an Object Manager for storage of
      medical images as one more data type associated to objects, and a support system
      developed to offer this kind of tool to medical application developers. The
      purpose of this work is to support the retrieval of images through queries based
      on the graphical contents of the stored images. The usual approach uses icons and
      textual attributes stored with the images to specify the queries. This work uses
      a novel modeling technique to define the "image data type," by means of which it
      is possible to decide, before the query itself, the key data of each image that
      must be extracted from the image when it is stored in the database, so the search
      can be accelerated when queries are issued. This approach enables building of
      expansible systems, where new image processing algorithms can be added easily,
      using its syntactic representation stored through an Image Meta-schema into the
      application database schema. This work shows how such a system has been
      implemented, and also provides a query language used to refer and execute these
      algorithms from inside the database management system.

PMID- 9555622
TI  - Anisakis, anisakiasis and IgE-mediated immunity to Anisakis simplex.
AB  - Anisakis simplex is a common parasite in fish and cephalopods and is not only
      capable of causing anisakiasis in humans through visceral invasion of the third
      stage larvae but can also cause anaphylactic reactions, as has recently been
      demonstrated. We present the clinical case of a 56-year-old man who initially
      presented anaphylactic reactions related to eating fish. Shortly afterwards, he
      began to experience self-limiting recurrences of very intense epigastric pain,
      nausea and vomiting. Skin tests for immediate hypersensitivity (prick tests) with
      a commercial extract as well as the determination of specific IgE in the
      patient's serum were clearly positive for A. simplex. The hemogram did not show
      eosinophilia. Copro-cultures and parasites in the patient's feces were repeatedly
      negative. Gastroscopy was normal. The intestinal tract showed contrast
      flocculation and dilation of ansas in the distal duodenum and proximal jejunum.
      Biopsy samples of gastric and distal duodenum mucous showed an active process of
      chronic inflammation with a predominance of eosinophils in the lamina propria.
      After subjecting the patient to a fish and cephalopod-free diet and treating him
      with thiabendazole 350 mg every 12 hours for 6 days, he showed no sign of
      symptoms while awaiting new tests. Even though the diagnosis of IgE-mediated
      allergy caused by A. simplex offers no room for doubt, we are unable to present a
      firm diagnosis of anisakiasis as no larva has been seen. Nevertheless, the
      clinical pattern, the image of the intestinal tract, the eosinophilic infiltrate
      in the biopsies and the good response to thiabendazole all lead to the suspected
      existence of anisakiasis in this patient coexisting with IgE-mediated allergy to
      this parasite.

PMID- 9555624
TI  - 3D reconstruction of tomographic images applied to largely spaced slices.
AB  - This paper presents a full reconstruction process of magnetic resonance images.
      The first step is to bring the acquired data from the frequency domain, using a
      Fast Fourier Transform algorithm. A Tomographic Image Interpolation is then used
      to transform a sequence of tomographic slices in an isotropic volume data set, a
      process also called 3D Reconstruction. This work describes an automatic method
      whose interpolation stage is based on a previous matching stage using Delaunay
      Triangulation. The reconstruction approach uses an extrapolation procedure that
      permits appropriate treatment of the boundaries of the object under analysis.

PMID- 9555625
TI  - LEMMA: a language for easy medical models analysis.
AB  - The quality of health care systems and processes is becoming a prominent problem
      and more and more efforts are devoted to define methodologies and tools to
      measure and assure quality of care. New methods are required to optimize health
      care processes to guarantee high quality standards within (limited) available
      resources. Resource optimizations able to preserve the quality of treatments
      require good models of medical processes. This paper presents LEMMA, a new
      notation to model medical processes. LEMMA provides physicians with intuitive
      graphical elements to design their models. At the same time a high level timed
      Petri net corresponding to the designed model is built automatically. In this
      way, LEMMA models are ascribed formal semantics and can be executed and analyzed
      automatically. The dual language approach followed in this paper allows
      physicians to gain all the benefits of formal methods without being proficient in
      them. Medical users manage simple graphical elements, while Petri nets ensure
      formality and validation capabilities. In this way LEMMA mixes formal and
      informal notations, overcoming the problems of both the approaches. The
      definition of the notation has been supported by the development of an
      environment to design LEMMA models. The environment, besides letting us
      experiment with the notation, has been employed to define and analyze real case
      studies.

PMID- 9555626
TI  - Using an artificial neural network to define the planning target volume in
      radiotherapy.
AB  - A neural network for predicting the planning target volume in radiotherapy from
      the shape of the detected tumor is designed and tested in this research project.
      The proposed neural network is able to generalize expert medical knowledge and
      predict the planning target volume from a three-dimensional image of the detected
      tumor. Initial results for simple shaped brain tumors are presented in this
      paper.

PMID- 9555627
TI  - The limitations of decision trees and automatic learning in real world medical
      decision making.
AB  - The decision tree approach is one of the most common approaches in automatic
      learning and decision making. The automatic learning of decision trees and their
      use usually show very good results in various "theoretical" environments. But in
      real life it is often impossible to find the desired number of representative
      training objects for various reasons. The lack of possibilities to measure
      attribute values, high cost and complexity of such measurements, and
      unavailability of all attributes at the same time are the typical
      representatives. For this reason we decided to use the decision trees not for
      their primary task--the decision making--but for outlining the most important
      attributes. This was possible by using a well-known property of the decision
      trees--their knowledge representation, which can be easily understood by humans.
      In a delicate field of medical decision making, we cannot allow ourselves to make
      any inaccurate decisions and the "tips," provided by the decision trees, can be
      of a great assistance. Our main interest was to discover a predisposition to two
      forms of acidosis: the metabolic acidosis and respiratory acidosis, which can
      both have serious effects on child's health. We decided to construct different
      decision trees from a set of training objects. Instead of using a test set for
      evaluation of a decision tree, we asked medical experts to take a closer look at
      the generated trees. They examined and evaluated the decision trees branch by
      branch. Their comments show that trees generated from the available training set
      mainly have surprisingly good branches, but on the other hand, for some, no
      medical explanation could be found.

PMID- 9555628
TI  - Genetic algorithm based system for patient scheduling in highly constrained
      situations.
AB  - In medicine and health care there are a lot of situations when patients have to
      be scheduled on different devices and/or with different physicians or therapists.
      It may concern preventive examinations, laboratory tests or convalescent
      therapies, therefore we are always looking for an optimal schedule that would
      result in finishing all the activities scheduled as soon as possible, with the
      least patient waiting time and maximum device utilization. Since patient
      scheduling is a highly complex problem, it is impossible to make a qualitative
      schedule by hand or even with exact heuristic methods. Therefore we developed a
      powerful automated scheduling method for highly constrained situations based on
      genetic algorithms and machine learning. In this paper we present the method,
      together with the whole process of schedule generation, the important parameters
      to direct the evolution and how the algorithm is guaranteed to produce only
      feasible solutions, not breaking any of the required constraints. We applied the
      described method to a problem of scheduling patients with different therapy needs
      to a limited number of therapeutic devices, but the algorithm can be easily
      modified for use in similar situations. The results are quite encouraging and
      since all the solutions are feasible, the method can be easily incorporated into
      an interactive user interface, which can be of major importance when scheduling
      patients, and human resources in general, is considered.

PMID- 9555629
TI  - Induction of decision trees and Bayesian classification applied to diagnosis of
      sport injuries.
AB  - Machine learning techniques can be used to extract knowledge from data stored in
      medical databases. In our application, various machine learning algorithms were
      used to extract diagnostic knowledge which may be used to support the diagnosis
      of sport injuries. The applied methods include variants of the Assistant
      algorithm for top-down induction of decision trees, and variants of the Bayesian
      classifier. The available dataset was insufficient for reliable diagnosis of all
      sport injuries considered by the system. Consequently, expert-defined diagnostic
      rules were added and used as pre-classifiers or as generators of additional
      training instances for diagnoses for which only few training examples were
      available. Experimental results show that the classification accuracy and the
      explanation capability of the naive Bayesian classifier with the fuzzy
      discretization of numerical attributes were superior to other methods and
      estimated as the most appropriate for practical use.

PMID- 9555630
TI  - Automated computer-assisted detection of follicles in ultrasound images of ovary.
AB  - Monitoring the follicles in women's ovaries is especially important in human
      reproduction. Today, the monitoring of follicles is done with human interaction.
      Such monitoring can be very demanding and inaccurate, and in most cases signifies
      additional burdens for the experts. In this paper, a new algorithm for automated
      computer-assisted detection of follicles in the ultrasound images of the ovary is
      proposed. It has a typical object recognition scheme (preprocessing,
      segmentation, and classification). The algorithm is based on the following idea:
      first, the ovary is estimated (coarsely) and then follicles are searched for. The
      methods used are known from literature (despeckle filter, Kirsch's operator,
      optimal thresholding, thinning, shape descriptions, classification), and the
      majority of our work was done experimenting with these methods and selecting the
      appropriate thresholds. The algorithm's computational complexity is of order of
      O(n2), which means about 6 min of processing time per an ultrasound image of
      dimensions of 768 x 576 pixels on HP 715 machines. It has been tested on a set of
      20 real ultrasound images of the ovary. The recognition rate of follicles with
      these procedures was around 62%. The algorithm is not perfect, but it will be
      further modified and improved, as indicated in our conclusions.

PMID- 9555631
TI  - Molecular medicine, managed care, and the moral responsibilities of patients and
      physicians.

PMID- 9555632
TI  - Genetic links, family ties, and social bonds: rights and responsibilities in the
      face of genetic knowledge.
AB  - Currently, some of the most significant moral issues involving genetic links
      relate to genetic knowledge. In this paper, instead of looking at the frequently
      addressed issues of responsibilities professionals or institutions have to
      individuals, I take up the question of what responsibilities individuals have to
      one another with respect to genetic knowledge. I address the questions of whether
      individuals have a moral right to pursue their own goals without contributing to
      society's knowledge of population genetics, without adding to their family's
      knowledge of its genetic history, and without discovering genetic information
      about themselves and their offspring. These questions lead to an examination of
      the presumed right to genetic ignorance and an exploration of a variety of social
      bonds. Analyzing cases in light of these considerations leads to a surprising
      conclusion about a widely accepted precept of genetic counseling, to some ethical
      insights into typical problems, and to some further unanswered questions about
      personal responsibility in the face of genetic knowledge.

PMID- 9555633
TI  - Responsibility, alcoholism, and liver transplantation.
AB  - Many believe that it is morally wrong to give lower priority for a liver
      transplant to alcoholics with end-stage liver disease than to patients whose
      disease is not alcohol-related. Presumably, alcoholism is a disease that results
      from factors beyond one's control and therefore one cannot be causally or morally
      responsible for alcoholism or the liver failure that results from it. Moreover,
      giving lower priority to alcoholics unfairly singles them out for the moral vice
      of heavy drinking. I argue that the etiology of alcoholism may involve enough
      control for the alcoholic to be responsible for his condition and accordingly
      have a weaker claim to receive a new liver than someone who acquires the disease
      through no fault of his own. In addition, I show why it is more plausible to
      reframe the question of priority in terms of control and responsibility rather
      than virtue and vice. Given that medical resources like livers are scarce, some
      people may justifiably be given lower priority than others in receiving these
      resources.

PMID- 9555634
TI  - Selection of recipients for donor organs in transplant medicine.
AB  - This paper deals with a problem which has received a great deal of attention in
      the ethical literature, but about which very little is known empirically: the
      selection of recipients for organs in transplant medicine. Based on a larger
      study, it is shown how this problem is practically resolved in one European
      country, Germany. It is demonstrated that most of the criteria used to determine
      recipients are non-medical in nature, even though they generally tend to be
      rationalized in medical terms. Moreover, the choice of criteria depends as much
      on prognostic considerations as on personal indiosyncrasies and values held by
      individual physicians who are in charge at the various programs. Several examples
      of the extremely diverse policies in which this results are presented.

PMID- 9555635
TI  - Patenting medical and surgical techniques: an ethical-legal analysis.
AB  - Considerable controversy has recently arisen regarding the patenting of medical
      and surgical processes in the United States. One such patent, viz. for a
      "chevron" incision used in ophthalmologic surgery, has especially occasioned
      heated response including a major, condemnatory ethics policy statement from the
      American Medical Association as well as federal legislation denying patent
      protection for most uses of a patented medical or surgical procedure. This
      article identifies and discusses the major legal, ethical and public policy
      considerations offered by proponents and opponents of such patents. The existing
      literature divides up into those who favor such patents essentially without
      qualification, and those who condemn and wish to outlaw them. We advance a
      compromise position where administrative and legislative action is called for to
      provide more specific guidelines regarding the patentability of such processes by
      the Patent and Trademark Office. Our position, in sum, will be that too much is
      at stake in this complicated area for either the blanket prohibition, or
      wholesale, uncritical acceptance, of the patenting of medical and surgical
      processes or techniques.

PMID- 9555636
TI  - A radical rupture in the paradigm of modern medicine: conflicts of interest,
      fiduciary obligations, and the scientific ideal.
AB  - Conflicts of interest serve as a cipher for a radical rupture in the Flexnerian
      paradigm of medicine, and they can only be addressed if we recognize that health
      care is now practiced by institutions, not just individual physicians. By showing
      how "appropriate utilization of services" or "that which is medically indicated"
      is a function of socioeconomic factors related to institutional responsibilities,
      I point toward an administrative and organizational ethic as a needed component
      for addressing conflicts of interest. The argument is developed by reviewing
      three important books. First, I consider Mark Rodwin's attempt to configure the
      economic structures of medicine so that classical fiduciary and scientific ideals
      can be fostered. Second, I consider E. Haavi Morreim's attempt to modify the
      classical ideals in order to account for new economic realities. Finally, by
      considering essays in a recent volume on conflicts of interest edited by Spece,
      Shimm, and Buchanan, I argue for a constructive dialectic between the approaches
      of Rodwin and Morreim. In order to properly address conflicts of interest, there
      must be a radical reassessment of medicine that accounts for the interrelation
      between scientific, ethical, and economic concerns. Until institutions come into
      view and professional ethics is developed to account for their role, legitimate
      interests and obligations of diverse parties cannot be harmonized.

PMID- 9555637
TI  - Combined management of intracranial vascular malformations in children.
AB  - We have reviewed 39 cases of intracranial vascular malformations, observed in the
      Section of Paediatric Neurosurgery of the Catholic University of Rome between
      1980 and 1995 (age 1-15 years). Diagnosis was of parenchimal AVM in 26 cases, in
      7 cases of AVM of the Galen region, in 5 cases of dural AVM and in 1 case of
      venous angioma. RESULTS AND CONCLUSIONS: Haemorrhage was the prevalent clinical
      onset in patients with parenchimal AVMs (57.7% of cases). Only one patient with a
      Galen region AVM presented cardiovascular symptoms, while 2/5 children observed
      for a dural AVM complained a congestive heart failure. Total surgical excision
      was performed in 17 of the 26 patients with parenchimal AVMs; moreover surgery
      was combined with preoperative endovascular embolization in 2 cases and with
      radiosurgery in 1 patient; we think that surgery is still the treatment of choice
      in patients with parenchimal AVMs. Endovascular treatment and radiosurgery have
      mainly an adjuvant role; nevertheless we agree that a preoperative endovascular
      management of parenchimal AVMs reduces the surgical risk, especially in cases of
      huge AVMs or AVMs localized in eloquent areas of the brain. Radiosurgery may be
      an alternative choice for complex or deeply sited AVMs; however in most cases, a
      combination with surgery or endovascular treatment is necessary to reduce the
      "target" size. AVM embolization was the only treatment in 2 of the 6 cases of
      dural AVMs; dural AVM embolization was combined with surgery in 1 case.
      Endovascular AVM exclusion is the treatment of choice in these patients. Surgery
      may be combined with endovascular treatment in case of a partial persistence of
      the AVM, or if signs of revascularization are present on control angiography. A
      conservative management is justified in patients with carotido-cavernous
      fistulae; in fact a complete spontaneous thrombosis is very frequent in these
      cases. A high rate of cardiovascular symptoms is reported in patients with Galen
      region AVMs diagnosed in the 1st year of life, but only 1 of our patients
      complained of congestive cardiac symptoms. Surgical treatment of Galen region
      AVMs is associated with a high morbidity and mortality. Actually a transarterial
      embolization of afferent vessels represents the treatment of choice in these
      patients; it can be combined with transvenous approach in case of complex AVMs
      and/or a non complete AVM exclusion.

PMID- 9555638
TI  - Endovascular treatment of pial AVMs: technical options, indications and limits in
      pediatric age patients.
AB  - Our study group consisted of 29 patients who underwent endovascular treatment for
      the presence of pial AVMs. The patients were treated with various embolization
      methods including "-free flow" embolization (2 cases); embolization with suture
      threads (2 mm long micro-emboli: 17 cases) and embolization with acrylic glue (10
      cases). There were significant angio-architectural and AVM location differences
      between the pediatric and the adult patient groups. In pediatric patients, the
      more frequent AVMs were of the mono or few-pedunculated type, then simple direct
      fistulas and high-flow fistulous-plexiform AVMs and giant infra-tentorial or deep
      seated malformations. In mono or few-pedunculated AVMs, the elected treatment was
      acrylic glue followed by radio-surgery achieving definitive cure in 3 cases. In
      direct AVFs and elevated flow AVMs, embolization with suture and acrylic glue
      offered definitive results. Treatment for infra-tentorial and deep-seated AVMs
      presented the greatest difficulty in pediatric patients. In two of them,
      embolization with glue enabled radiosurgery (giant cerebellar AVMs). Our
      experience did not confirm that current endovascular techniques provide
      definitive treatment in extensive, deep-seated AVMs. Each treatment, in children
      more so than in adults, requires a risk/benefit evaluation of the method taking
      into account the natural history data.

PMID- 9555639
TI  - Comparison of pediatric and adult cerebral arteriovenous malformations.
AB  - The authors report 19 consecutive children with cerebral arteriovenous
      malformations over the period 1978-1992. These patients are compared with a
      series of 120 consecutive adult patients with the same pathology, managed during
      the same period. The main clinical and angiographic features, as well as the
      treatment modalities and outcome are reviewed and compared. Children seem to
      harbour smaller and simpler lesions than adults. Furthermore, despite a more
      severe clinical presentation, children appears to fare better than adults. The
      possibility of evolution of brain arteriovenous malformations is discussed.

PMID- 9555640
TI  - Complex arteriovenous fistula of the brain in an infant. Case report.
AB  - A rare case of complex cerebral arteriovenous fistula in an infant is reported.
      An 8-month-old boy first presented with a syndrome of increased intracranial
      pressure. Neuroradiological assessment showed a direct intracerebral
      arteriovenous shunt with marked venous engorgement. No hemorrhage was evident.
      Direct surgical treatment was decided. Clinical and radioanatomical cure was
      achieved. The main angiographic and pathophysiologic features of this unusual
      entity, as well as the available therapeutic options, are reviewed and discussed.

PMID- 9555641
TI  - Surgical management of paediatric cerebral cavernomas.
AB  - Over the past 15 years (1981-1995) 24 children with cerebral cavernous angiomas
      have been treated surgically at the Section of Pediatric Neurosurgery of the
      Catholic University of Rome. The most common symptoms at presentation were
      epilepsy (13 children) and intracranial hypertension (9 children). None of these
      patients had a family history of cerebro-vascular malformations. Multiple lesions
      were detected in two subjects. In 19 cases, radiological signs of significant
      acute and subacute hemorrhage were present at the radiological examinations. The
      supratentorial compartment was the most frequent localization of the lesions,
      with only four cavernomas observed in the subtentorial space. The post-surgical
      results were good: only nine children had a persistence of the presurgical
      neurological signs, although ameliorated by the treatment; no patient showed a
      progression of pre-operative neurological signs, neither the onset of new
      deficits; only one child died, but his clinical conditions were very critical
      before surgery. Our results suggest that the youngest children present with
      evidence of significant hemorrhages more frequently than their older counterpart.
      In our series, the removal of cavernomas allowed to control the seizure disorders
      in all the case, thus suggesting that in this type of malformative lesion,
      lesionectomy alone may be sufficient to resolve epilepsy.

PMID- 9555642
TI  - Giant intracavernous carotid aneurysm in a child. Case report.
AB  - The occurrence of intracranial aneurysm in the pediatric population is a rare
      phenomenon. A case of giant aneurysm of the intracavernous carotid artery in a
      child is reported. Clinicoradiological findings are presented and the surgical
      procedure is illustrated. Authors stress the value of monitoring the cerebral
      collateral blood flow before and during the operation.

PMID- 9555643
TI  - Cerebral cavernous angiomas in critical areas. Reports of three cases in
      children.
AB  - Cerebral cavernous angiomas are congenital malformations usually presenting with
      symptomatic hemorrhages or seizures. The advent of MRI has allowed to detect
      asymptomatic, "cryptic" brain cavernomas. They can occur in a sporadic, isolated
      form and in a familial form characterized by multiple lesions. Surgical treatment
      is recommended by most authors in symptomatic cases when the lesion is isolated
      and readily accessible. Treatment is more controversial when the vascular
      malformation is located in critical brain region. On the other hand the increased
      risk of rebleeding after a prior hemorrhage and the decreased effectiveness of
      lesionectomy in patients with a long seizure history could lead to perform an
      early surgical excision also for cavernous angiomas located in those areas. We
      report three cases of symptomatic cerebral cavernomas located in critical areas,
      in children. In all cases the surgical removal of the lesions was successfully
      performed. The two cases presented with seizures are seizure-free in spite of the
      interruption of the antiepileptic therapy. The patient presented with
      neurological deficit due to intraparenchymal hemorrhage progressively recovered
      his motor function. Our experience seems to confirm the value of surgical removal
      regardless of where the cavernoma is located.

PMID- 9555644
TI  - Stereotactic radiosurgery for the treatment of arteriovenous malformations in
      childhood.
AB  - BACKGROUND: The main techniques and results in stereotactic radiosurgical
      treatment of endocranial AVM's are described and compared. The authors also
      report their preliminary experience in the treatment of 6 consecutive pediatric
      patients with intracerebral vascular malformations using gamma knife (GK)
      radiosurgery. METHODS: The various stereotactic radiosurgery methods currently
      used (charged-particle beam, modified linear accelerator, and GK) are described.
      At the Department of Neurosurgery in Verona, from February 1993 to February 1996,
      stereotactic GK radiosurgery was performed on 721 patients, including 20 of
      pediatric age (3%). Of the 78 AVMs, 7 (9%) were diagnosed in children. One
      patient was lost at follow-up. Among the remaining 6 children, there were 3 males
      and 3 females with a mean age of 12.3 years (range, 5-16 years). Treatment
      general anesthesia was needed only in 1 case. The AVM volume was always less than
      10 cc. After completion of the procedure, children were discharged from the
      hospital the following day. RESULTS: The follow-up period ranged from 4 months to
      29 months (median 18.8 months). The angiographic confirmed total obliteration is
      used as the end point of an AVM treated radiosurgically, and usually requires 2
      to 3 years. All the patients are alive; four of the treated children are
      neurologically normal and one patient has clinically improved to a normal
      neurological status. The sixth patient has fixed neurological deficits that
      existed prior to treatment. Among the three cases with a follow-up period of over
      2 years, complete obliteration has been angiographically confirmed in 2 patients
      and subtotal in 1 patient. In the three remaining patients with follow-up periods
      less than 2 years, serial MR images suggest subtotal obliteration in 2 cases and
      no significant change in one patient who had undergone treatment within the
      current year. To date, neither persistent GK radiosurgery-related complications
      nor bleeding following stereotactic radiosurgery has been described. CONCLUSIONS:
      The review of literature and our preliminary results suggest that also in
      children, as in adults, the use of stereotactically delivered irradiation
      represents a safe and effective technique obtaining complete obliteration of AVMs
      previously considered surgically inaccessible due to their location and poor
      response to resection and/or embolization.

PMID- 9555645
TI  - Activated protein C resistance due to a factor V mutation associated with
      familial ischemic stroke.
AB  - Recent findings have indicated the association between activated protein C (APC)
      resistance and cerebrovascular disease. These reports prompted us to investigate
      whether resistance to APC could be found in patients suffering from transient
      ischaemic attacks or stroke. Therefore, we studied APC-resistance in 14 young
      adults belonging to three different families with a history of transient ischemic
      attacks (TIAs) and stroke. Nine out of fourteen subjects showed APC-resistance
      but no deficiencies in the anticoagulant proteins AT III, PC and PS. The family
      history demonstrated a distribution of APC-resistance compatible with dominant
      autosomal inheritance. A rapid screening method to detect factor V R506Q (Leiden)
      mutation without sequencing or restriction enzyme digestion has been set-up after
      biochemical analyses. DNA analysis showed a guanine to adenine transition at
      nucleotide 1,691 in patients and their relatives with poor response to activated
      protein C detected by APTT tests. Of 14 investigated subjects and their family
      members, 5 were normals, 6 were heterozygotes and 3 were homozygotes for factor V
      mutation. The mutation, in heterozygous form, was also found in 1.3% of our
      normal population (n = 75). Our findings indicate a possible involvement of APC
      resistance in the pathogenesis of arterial thrombosis in young adults.

PMID- 9555646
TI  - Blood degradation products play a role in cerebral ischemia caused by acute
      subdural hematoma.
AB  - The pathogenesis of ischemic brain lesions with traumatic hematoma is
      multifactorial. It has been suggested that the presence of subdural hematoma in
      patients with severe head injury is associated with elevated intracranial
      pressure and higher mortality. In this study we created acute subdural mass in
      the rats by injecting 250 microliters of autologous blood and silicone oil into
      the subdural space. The goal of this study was to determine the effect of
      subdural hematoma versus silicone oil on the adjacent brain parenchyma. Twenty
      four hours after the injection, of the hematoma in the subdural space in rats
      produced an extensive zone of underlying ischemic damage but silicone oil did
      not. This study has shown that pressure alone caused by silicone oil is
      insufficient to cause significant neuronal damage or loss.

PMID- 9555647
TI  - The postero-lateral approach in the treatment of post-traumatic canalar stenosis
      of the thoraco-lumbar spine.
AB  - METHODS: Twenty-four cases of unstable thoraco-lumbar fractures with significant
      canalar stenosis were operated in the Emergency Neurosurgical Unit of the
      Cardarelli Hospital from November 1989 to October 1991. The surgical technique
      was the combined transpedicular (TPA) and transarticular (TAA) postero-lateral
      approach, posterior osteosynthesis and arthrodesis. The average follow-up was 20
      months. RESULTS: No evidence of implant breakage or pseudoarthrosis was detected.
      CONCLUSIONS: The authors affirm recalibration of the posterior wall by direct
      impaction, epidural hemostasis, removal of extruded disc fragments and dural
      repair are the advantages offered by this technique without compromise the
      contsrist stability. This approach represents an alternative to single posterior
      and combined anterior-posterior approaches in the management of the thoraco
      lumbar fractures with severe canal stenosis.

PMID- 9555648
TI  - Infected cerebral hemorrhage by ruptured infectious anterior communicating artery
      giant aneurysm in a patient with T cell acute lymphoblastic leukemia. Case
      report.
AB  - Although the majority of infectious (bacterial) intracranial aneurysms occur in
      patients with subacute bacterial endocarditis, septic cerebral embolization and
      infectious intracranial aneurysm formation can also occur in immunocompromised
      patients. We report the case of ruptured bacterial aneurysm occurring in a 19
      years old man immunocompromised by vigorously treated acute lymphoblastic
      leukemia. This case confirms very poor prognosis for infectious aneurysms in
      immunocompromised patient reported in literature, suggesting that a high index of
      suspicion needs for early diagnosis and that a conservative approach (high dose
      antibiotic therapy with possible delayed surgery) should be preferred unless
      intracerebral hemorrhage or abscess with significant mass effect provides a clear
      indication for operative intervention.

PMID- 9555649
TI  - Lateral ventricle subependymomas. Case report taking into particular
      consideration the aspects of magnetic resonance and review of the literature.
AB  - Subependymomas are rare neuroectodermic tumours. The authors report a case of a
      patient he had a subendymoma in the left lateral ventricle, with particular
      attention to the MR aspects on these lesions and review of the literature.

PMID- 9555650
TI  - Exophytic pontine glioblastoma mimicking acoustic neuroma.
AB  - A 22-year-old male with unilateral facial, cochlear and glossopharyngeal cranial
      nerve dysfunction and ataxia that was slowly progressive over one year is
      described. Although clinically it was considered he probably had an acoustic
      neuroma, surgery revealed a pontine glioblastoma exophytic into the
      cerebellopontine angle and internal acoustic meatus. Clinicoradiological features
      that distinguish this extremely rare lesion of the hindbrain from acoustic
      neuroma are discussed.

PMID- 9555651
TI  - Radiation-induced cerebral meningiomas. Case reports.
AB  - Two cases are presented of meningiomas following external cranial irradiation in
      which several features clearly indicate a causal relationship between
      radiotherapy and tumour development. In one patient multiple recurred meningioma
      was diagnosed 30 years after low-dose X-ray treatment of Tinea capitis; in the
      other patient the meningioma was diagnosed approximately 18 years after high-dose
      radiation therapy for astrocytoma. The features distinguishing radiation-induced
      meningiomas from other meningiomas are reviewed. The use of radiation therapy
      only in those cases in which there is clear evidence that it will have beneficial
      effects and that these effects will outweigh the risks is emphasized.

PMID- 9555652
TI  - Cavernous hemangioma of the skull. Case report and review of the literature.
AB  - Osseous hemangiomas are rare skeletal tumors that constitute 0.7% of all osseous
      neoplasms. The most common site is the vertebral column while involvement of the
      calvarium is extremely rare accounting for 0.2% of all bone neoplasm. The authors
      present a case of a 35-years-old man who was admitted with right parietal
      swelling and review the gross appearance, pathogenesis, histopathology,
      radiological features and treatment of this neoplasm.

PMID- 9555653
TI  - Spontaneous movement of metallic foreign bodies. Case report.
AB  - We report a case of missile injury to the brain with an unusual complication. The
      bullet migrated by its mere weight to a distant location through the brain
      parenchyma after initially lodged in a superficial site. Movement of the bullet
      was first detected on CT scan and the significance and treatment of this finding
      is emphasized.

PMID- 9555654
TI  - The cytochrome P-450 inhibitor cobalt chloride prevents inhibition of renal Na,K
      ATPase and redistribution of apical NHE-3 during acute hypertension.
AB  - Acute systolic arterial hypertension provokes a rapid decrease in proximal tubule
      sodium reabsorption and diuresis associated with inhibition of renal cortex Na,K
      ATPase activity and redistribution of apical membrane Na/H exchanger (NHE-3) to
      heavier density membranes containing markers of intermicrovillar cleft and
      endosomes. Because cytochrome P-450-dependent arachidonate metabolites
      participate in the regulation of renal sodium transport and BP, this study tested
      the hypothesis that these renal responses to acute hypertension would be
      prevented if cytochrome P-450 metabolism were inhibited by cobalt chloride
      (CoCl2). Four groups of rats (n = 4 to 5) were studied: (1) sham-operated; (2) 50
      mg of CoCl2/kg subcutaneously for 2 d; (3) acute hypertension by constricting
      arteries for 5 min; and (4) acute hypertension after CoCl2 treatment as in group
      3. Renal cortex was analyzed after sorbitol density gradient fractionation. CoCl2
      treatment alone did not significantly affect the rate of urine output, endogenous
      lithium clearance (an inverse measure of proximal tubule sodium reabsorption),
      maximal activity of Na,K-ATPase, or subcellular distribution of NHE-3-containing
      membranes. In non-CoCl2-treated animals, acute hypertension provoked a three- to
      fourfold increase in urine output and endogenous lithium clearance, 33%
      inhibition of renal cortex Na,K-ATPase activity, and redistribution of NHE-3 out
      of the apical membrane peak. In CoCl2-treated animals, acute urine output and
      endogenous lithium clearance increased only twofold during acute hypertension,
      there was no inhibition of Na,K-ATPase activity, and there was no redistribution
      of NHE-3 immunoreactivity to higher density membranes. These findings demonstrate
      that CoCl2 treatment both attenuates the inhibition of proximal tubule sodium
      reabsorption and diuresis and abolishes Na,K-ATPase inhibition and NHE-3
      redistribution during acute hypertension, evidence that these responses may be
      mediated by cytochrome P-450 arachidonate metabolites.

PMID- 9555655
TI  - Regulation of Na+, K(+)-ATPase in the rat outer medullary collecting duct during
      potassium depletion.
AB  - Because in outer medullary collecting ducts (OMCD) of K(+)-depleted rats, K+
      secretion is abolished, whereas Na+, K(+)-ATPase, which energizes this secretion,
      is markedly stimulated, it has been proposed that Na+, K(+)-ATPase was mislocated
      to the apical cell membrane and energized K+ reabsorption. This hypothesis has
      been supported by paradoxical effects of ouabain in K(+)-depleted compared with
      normal rats. However, we have recently shown that ouabain inhibits not only Na+,
      K(+)-ATPase but also apical H+, K(+)-ATPase in the OMCD of K(+)-depleted rats.
      Therefore, this study was designed to evaluate whether previous observations were
      accounted for by Na+, K(+)-ATPase or by ouabain-sensitive H+, K(+)-ATPase. Na+,
      K(+)-ATPase was distinguished from H+, K(+)-ATPase by its insensitivity to Sch
      28080. Results indicate that the hydrolytic and transport activities of Na+, K(+)
      ATPase, the number of its functional units, and the expression of mRNA of its
      alpha 1 and beta 1 subunits were increased threefold or more in the OMCD of rats
      fed a K(+)-depleted diet for 2 wk. By immunofluorescence, Na+, K(+)-ATPase
      staining was strongly increased in K(+)-depleted rats but remained localized to
      the basolateral pole of OMCD principal cells. In conclusion, K+ depletion is
      associated with marked induction of functional Na+, K+ pumps at the basolateral
      pole of rat OMCD. Therefore, reduced K+ secretion might result from inhibition of
      apical K+ conductances and stimulation of basolateral K+ recycling. It is
      proposed that increased Na+, K(+)-ATPase participates in the increased Na+
      reabsorption prevailing in collecting ducts of K(+)-depleted rats.

PMID- 9555656
TI  - Participation of mercuric conjugates of cysteine, homocysteine, and N
      acetylcysteine in mechanisms involved in the renal tubular uptake of inorganic
      mercury.
AB  - Mechanisms involved in the renal uptake of inorganic mercury were studied in rats
      administered a nontoxic 0.5 mumol/kg intravenous dose of inorganic mercury with
      or without 2.0 mumol/kg cysteine, homocysteine, or N-acetylcysteine. The renal
      disposition of mercury was studied 1 h after treatment in normal rats and rats
      that had undergone bilateral ureteral ligation. In addition, the disposition of
      mercury (including the urinary and fecal excretion of mercury) was evaluated 24 h
      after treatment. In normal rats, coadministering inorganic mercury plus cysteine
      or homocysteine caused a significant increase in the renal uptake of mercury 1 h
      after treatment. The enhanced renal uptake of mercury was due to increased uptake
      of mercury in the renal outer stripe of the outer medulla and/or renal cortex.
      Ureteral ligation caused reductions in the renal uptake of mercury in all groups
      except for the one treated with inorganic mercury plus N-acetylcysteine. Thus, it
      appears that virtually all of the mercury taken up by the kidneys of the normal
      rats treated with inorganic mercury plus N-acetylcysteine occurred at the
      basolateral membrane. Urinary excretory data also support this notion, in that
      the rate of excretion of inorganic mercury was greatest in the rats treated with
      inorganic mercury plus N-acetylcysteine. Our data also indicate that uptake of
      inorganic mercury in the kidneys of rats treated with inorganic mercury plus
      cysteine occurred equally at both luminal and basolateral membranes. In addition,
      the renal uptake of mercury in rats treated with inorganic mercury plus
      homocysteine occurred predominantly at the basolateral membrane with some
      component of luminal uptake. The findings of the present study confirm that there
      are at least two distinct mechanisms involved in the renal uptake of inorganic
      mercury, with one mechanism located on the luminal membrane and the other located
      on the basolateral membrane. Our findings also show that cysteine and homologs of
      cysteine, when coadministered with inorganic mercury, greatly influence the
      magnitude and/or site of uptake of mercuric ions in the kidney.

PMID- 9555657
TI  - Renal impairment in chronic cigarette smokers.
AB  - To determine the effect of chronic cigarette smoking on renal function, a cross
      sectional study was carried out with 30 subjects who had no known vascular
      disease risk factor other than cigarette smoking, and 24 age- and sex-matched
      controls without any vascular risk factor including cigarette smoking. Renal
      function by radionuclide studies of renal plasma flow, GFR, and plasma endothelin
      1 concentration was determined. Compared with nonsmokers, smokers had a renal
      function impairment characterized by a normal GFR and a significant reduction in
      renal plasma flow as reflected by MAG3 clearance (199.20 +/- 58.85 ml/min per
      1.73 m2 versus 256.54 +/- 60.14 ml/min per 1.73 m2; t = 3.52, P < 0.001). MAG3
      clearance was significantly correlated with age and smoking. The renal
      dysfunction was associated with an increase in plasma endothelin-1 concentration
      (21.56 +/- 1.15 pmol/L versus 25.01 +/- 3.21 pmol/L; t = 5.00, P < 0.001). Former
      smokers as well had similar, although milder, abnormalities. In conclusion,
      cigarette smokers manifest an impairment of renal function, suggesting that smoke
      may have a detrimental effect on renal function.

PMID- 9555658
TI  - Mesangial cells possess an asialoglycoprotein receptor with affinity for human
      immunoglobulin A.
AB  - Asialoglycoprotein receptor (ASGP-R), a hepatic lectin involved in the clearance
      of galactose-terminal glycoproteins, is also present in extrahepatic tissues, but
      its expression in renal cells is not well established. This study examines the
      presence of ASGP-R in cultured mesangial cells (MC), key cells involved in the
      removal of macromolecules deposited in the glomerulus. The binding of asialo
      orosomucoid (ASOR) to rat MC was saturable and galactose-specific. In addition,
      MC internalized and degraded ASOR in a Ca(2+)-dependent manner. Parallel studies
      were performed in a homologous system (human MC), obtaining similar binding curve
      and competition with unlabeled ASOR and carbohydrates. The purified receptor from
      rat MC consisted of two proteins (41 and 55 kD) with similar size to the hepatic
      receptor. Both subunits were detected by mRNA expression analysis (ratio 2:1).
      Because the hepatic receptor presents avidity for the carbohydrates of IgA1, a
      protein deposited in the glomerulus of patients with IgA nephropathy, the
      interaction of IgA1 with the mesangial ASGP-R was explored. As for the
      interaction with ASOR, catabolism of IgA1 by rat and human MC was Ca(2+)
      dependent and was reduced with galactose. In addition, the interaction of ASOR
      with rat MC was partially inhibited by incubation with IgA1 and its desialylated
      form, but not by IgA2, as demonstrated in binding experiments and in receptor
      purification. It is concluded that MC possess ASGP-R specific for galactose
      residues of several glycoproteins, including IgA1. These data could be important
      for a better understanding of the pathogenesis of IgA nephropathy.

PMID- 9555659
TI  - Analyses of IgA1 hinge glycopeptides in IgA nephropathy by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - This study was performed to analyze the structural variety of O-glycans on the
      IgA1 hinge in IgA nephropathy (IgAN). The IgA1 fragments containing the hinge
      glycopeptide (33-mer hinge peptide core (HP) + O-glycans) were separated from 13
      IgAN patients, eight healthy control subjects, and 11 patients with other primary
      glomerulonephritides by pyridylethylation, trypsin treatment, and Jacalin
      affinity chromatography. Because of the use of Jacalin, only the Gal beta 1
      3GalNAc residue containing IgA was analyzed. The molecular weights (MW) of the
      IgA1 fragments treated by the following sequential treatment by exoglycosidases
      were estimated using matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry: (1) Sialidase treatment: the MW of the two observed peaks A
      and B were compatible with (A) HP + 4GalNAc + 4Gal and (B) HP + 5GalNAc + 4Gal.
      (2) Sialidase and galactosidase: the MW of the two identified peaks a and b were
      consistent with (a) HP + 4GalNAc and (b) HP + 5GalNAc. (3) Sialidase,
      galactosidase, and alpha-N-acetylgalactosaminidase. All subjects revealed one
      peak, indicating the 33-mer IgA1 hinge peptide core. The intensity rate of peak
      B/A was significantly decreased in the IgAN group (mean +/- SD, 1.01 +/- 0.08)
      compared with the negative control subjects (healthy group, 1.15 +/- 0.06, P =
      0.0048; other glomerulonephritis group, 1.13 +/- 0.10, P = 0.0049; Scheffe's F
      test). These results suggested the presence of a defect in the Gal and/or GalNAc
      residues in the IgA1 hinge glycopeptides in IgAN.

PMID- 9555660
TI  - Thrombin regulates PDGF expression in bovine glomerular endothelial cells.
AB  - The proteolytic enzyme thrombin is produced during activation of the coagulation
      pathway. Intraglomerular fibrin deposition and thrombosis are common pathologic
      features of several glomerular diseases, including transplant rejection. The
      effect of thrombin on platelet-derived growth factor (PDGF) production and DNA
      synthesis in well characterized bovine glomerular endothelial cells (G/endo) was
      studied. DNA synthesis was measured as the amount of [3H]thymidine incorporated
      into acid-insoluble material. PDGF released in the supernatant was measured by
      Western blotting and by a radioreceptor assay. PDGF mRNA expression was analyzed
      by solution hybridization, using human genomic PDGF B-chain (c-sis) and A-chain
      cDNA probes. G/endo constitutively secrete PDGF activity in serum-free medium.
      Thrombin stimulates PDGF production and increases the expression of mRNA that
      hybridizes with labeled B-chain but not A-chain probe, whereas epidermal growth
      factor and transforming growth factor-alpha stimulate the expression of PDGF A
      chain mRNA. In addition, thrombin stimulates DNA synthesis with a peak effect at
      24 h. Unlike endothelial cells from other microvascular beds, G/endo did not
      respond to any of the three PDGF isoforms BB, AB, or AA. These data demonstrate
      that bovine G/endo produce PDGF and that thrombin stimulates de novo synthesis of
      PDGF from these cells. Because mesangial, but not bovine, G/endo express PDGF
      receptors, PDGF released by G/endo is likely to modulate mesangial cell functions
      such as proliferation and matrix production by means of a paracrine mechanism.

PMID- 9555661
TI  - CD59 protects glomerular endothelial cells from immune-mediated thrombotic
      microangiopathy in rats.
AB  - CD59 is a cell membrane-bound complement regulatory protein on glomerular cells
      that inhibits C5b-9 assembly and insertion. This report describes a recently
      developed model of immune thrombotic microangiopathy (TMA) induced by the renal
      artery perfusion of anti-glomerular endothelial cell (anti-GEN) antibody. To
      examine the role of CD59 in protecting the GEN from immune-mediated injury, rats
      underwent selective renal artery perfusion with F(ab')2 fragments of anti-CD59
      monoclonal antibody to block CD59 activity or control mouse IgG followed by anti
      GEN antibody or control goat IgG. Neutralization of CD59 in normal rats did not
      result in any significant functional or histologic changes. Perfusion with anti
      CD59 did not change deposition of the pathogenic anti-GEN IgG used to induce the
      TMA model. However, neutralization of CD59 in the TMA model resulted in more C5b
      9 formation in glomeruli, accompanied by increased platelet and fibrin
      deposition, more severe endothelial injury, and reduced renal function compared
      with the animals perfused with control F(ab')2 fragments. These results
      demonstrate directly that CD59 serves a protective role for GEN in this TMA model
      of rats, and confirm that C5b-9 formation has a critical pathogenic role in the
      mediation of the disease. CD59 may play an important role in protecting
      glomerular endothelium from other complement-mediated types of injury.

PMID- 9555662
TI  - Characterization of two polymorphic sites in the human kinin B1 receptor gene:
      altered frequency of an allele in patients with a history of end-stage renal
      failure.
AB  - On the basis of the genomic structure of the human B1 receptor (B1R) for kinins,
      the presence of possible allelic polymorphisms of this gene was investigated
      using restriction fragment-length polymorphism and single-strand conformation
      polymorphism. The frequencies of the found alleles were determined in healthy
      volunteers and in patients with a history of end-stage renal failure, because
      there is evidence for a nephroprotective action of the kallikrein-kinin system.
      An A1098-->G polymorphism has been identified in exon 3 in a minority of
      volunteer blood donors, and is located 35 nucleotides downstream from the stop
      codon and 14 nucleotides upstream from the polyadenylation signal. The frequency
      of the G allele is 4.4% in the control sample and not significantly altered in
      patients with a history of end-stage renal failure. A second and more frequent
      polymorphism (18.1% of the alleles in the control group, prevalence of 33.3%)
      consists of a single base substitution (G-699-->C) in the putative promoter
      region. This polymorphism is significantly less frequent in the population of
      renal failure patients (prevalence of 20.6%) and determines an increased activity
      of the promoter function in constructions involving a reporter gene. The altered
      prevalence of this allele was also found in some etiologic subgroups of uremic
      patients. This study confirms the mapping of the B1R gene to 14q32. Other
      investigators have mapped the bradykinin B2 receptor (B2R) gene to a close site
      on human chromosome 14. A previously described B2R polymorphism (exon 2, C181-
      >T) had an allele frequency of 9.7% in the control sample and appears to be
      clinically neutral. The polymorphism of the B1R promoter may be a marker of
      prognostic significance for the preservation of renal function in diseased
      individuals.

PMID- 9555663
TI  - A possible molecular basis of natriuresis during ischemic-reperfusion injury in
      the kidney.
AB  - Ischemic renal injury is associated with increased fractional excretion of
      sodium, suggesting a Na+ reabsorption deficiency in renal tubules. To determine
      whether alterations in expression of the major Na+ transporter genes might
      contribute to the natriuresis that follows ischemic acute renal failure, the
      expression of these genes was analyzed in renal cortex and medulla after ischemic
      reperfusion injury. Rats were subjected to 30 min of renal pedicle clamping and
      then sacrificed at 12, 24, or 48 h after reperfusion. Serum creatinine increased
      significantly at 12 and 24 h, indicative of acute renal failure, but decreased
      substantially by 48 h. mRNA levels for the NHE-3 Na/H exchanger of the proximal
      tubule, the apical Na-K-2Cl cotransporter of the thick ascending limb of Henle,
      the Na-Cl cotransporter of the distal convoluted tubule, the epithelial Na+
      channel of the collecting duct, and the basolateral Na(+)-K(+)-ATPase were
      measured by Northern hybridization. NHE-3 mRNA decreased by approximately 75% at
      12 h and remained suppressed at 24 and 48 h after reperfusion. Na-K-2Cl
      cotransporter mRNA decreased by approximately 88% at 12 h and remained suppressed
      at 24 and 48 h. Na-Cl cotransporter mRNA remained unchanged at 12 h, decreased by
      approximately 60% at 24 h, and returned to almost control levels at 48 h. mRNA
      levels for sodium channels (beta subunit) remained unchanged. Na(+)-K(+)-ATPase
      mRNA in the medulla decreased by approximately 35 to 40% at 12 and 24 h and by
      70% at 48 h, whereas in cortex it decreased by only < 15% at 12 or 48 h after
      reperfusion. These results suggest that sharp reductions in expression of the NHE
      3 Na/H exchanger and the apical Na-K-2Cl cotransporter are major factors in the
      natriuresis/diuresis that is one of the hallmarks of ischemic acute renal
      failure. Lasting suppression of these transporters, despite improvement in renal
      function, could contribute to the deranged NaCl and water excretion that often
      leads to volume depletion during recovery from ischemic acute renal failure.

PMID- 9555664
TI  - Role of IL-1 in renal ischemic reperfusion injury.
AB  - Interleukin-1 (IL-1) is a central component of many acute inflammatory processes.
      Blocking IL-1 receptor (IL-1R) with IL-1R antagonist (IL-1Ra) has attenuated
      ischemic reperfusion injury in brain, heart, and liver models. However, the role
      of IL-1 in renal ischemic reperfusion injury (IRI) is not known. Therefore, the
      role of IL-1 in renal IRI was evaluated using the complementary approaches of IL
      1R blockade in wild-type mice in addition to the study of renal IRI in IL-1R
      knockout (KO) mice. Ischemia was induced by bilateral renal pedicle clamping for
      30 min. IL-1Ra was administered at 10 mg/kg every 4 h, high doses that have been
      protective in previous organ injury models in mice. IL-1R KO animals, previously
      characterized as insensitive to IL-1, had the absence of IL-1R1 confirmed by DNA
      blots. IL-1Ra, IL-1R KO, and control groups had similar elevations of blood urea
      nitrogen (114 +/- 13, 133 +/- 11, and 120 +/- 11 mg/dl) and serum creatinine (1.7
      +/- 0.3, 2.1 +/- 0.2, and 1.6 +/- 0.3 mg/dl) 24 h after ischemia. Furthermore,
      acute tubular necrosis scores were also similar in IL-1Ra-treated mice (3.0 +/-
      0.3), IL-1R KO mice (2.7 +/- 0.3), and control mice (3.1 +/- 0.2). However, both
      IL-1Ra and IL-1R KO groups, compared with control animals, developed
      significantly less infiltration of polymorphonuclear leukocytes per 10 high-power
      fields in postischemic renal tissue (1111 +/- 228 and 967 +/- 198 versus 1820 +/-
      190, P < 0.05). In contrast to the comparable renal functions at 24 h, recovery
      of renal function was significantly accelerated in the IL-1R KO group compared
      with control at both 48 (P < 0.05) and 72 (P < 0.05) h. Recovery in the IL-1Ra
      group was similar to that in the control animals. These data demonstrate that IL
      1 is unlikely to be beneficial in the recovery of renal function after ischemia
      and may play a deleterious role.

PMID- 9555665
TI  - Induction of apoptosis in ischemia-reperfusion model of mouse kidney: possible
      involvement of Fas.
AB  - Although ischemia-reperfusion of mouse kidney is known to cause severe renal
      failure due to tubular cell death, the exact cellular mechanism responsible for
      this phenomenon is not clear. To investigate the spatial and temporal development
      of renal cell death and the role of Fas/APO-1/CD95 (Fas) in this process, the
      left renal vessels were occluded in a group of mice for 30, 60, or 120 min
      followed by reperfusion for 24 h (n = 4 for each group). Analysis of the isolated
      DNA in agarose-gel electrophoresis revealed a typical ladder pattern of bands
      consisting of multiples of 180 to 200 bp, considered the hallmark of apoptosis.
      The intensity of the bands increased proportionately with the duration of
      ischemia. Histochemical analysis using terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling showed the presence of nuclei with DNA
      double-strand breaks specifically in distal renal tubules of the outer medulla.
      The presence of apoptosis was also confirmed by electron microscopy. Analysis of
      total RNA by Northern blotting revealed one appropriate-sized band for Fas mRNA
      in the normal kidney, which intensified in the ischemia-reperfused kidney.
      Moreover, nonradioactive in situ hybridization revealed that distal renal tubular
      epithelial cells were positive for Fas mRNA in the outer medulla. Fas antigen was
      also localized to the renal tubular epithelial cells of the outer medulla by
      immunohistochemistry. The number of apoptotic cells in the ischemia-reperfusion
      kidney of the lpr/lpr mouse was low. These findings strongly indicate that
      ischemia-reperfusion of the kidney induces apoptosis of a specific area of
      tubular epithelial cells in the outer medulla through the Fas system.

PMID- 9555666
TI  - Evolution of tubulointerstitial fibrosis in experimental renal infection and
      scarring.
AB  - Renal tubulointerstitial fibrosis may result from a loss of tubulointerstitial
      volume, which produces a disproportionate increase in the density of matrix. This
      study examines the relationship between fibrogenesis and collapse in scar
      formation after experimental renal infection. Escherichia coli were inoculated
      into the renal cortex of Sprague Dawley rats, with saline substituted in a
      control group. Glomerular, tubular, and interstitial profile areas were
      determined. Density of glomerular profiles was used as a measure of
      tubulointerstitial collapse. Collagen type I, III, and IV expression was examined
      by in situ hybridization and immunohistochemistry. Myofibroblasts were identified
      by alpha smooth muscle actin immunohistochemistry, and matrix metalloproteinase-1
      (MMP-1) and MMP-2 were localized with appropriate antisera. Acute interstitial
      edema was followed by increasing density of glomerular profiles, paralleled by
      loss of interstitial volume and progressive tubular atrophy. Glomerular profile
      area remained unchanged. Density of glomerular profiles was not temporally
      related to myofibroblast accumulation. Procollagen alpha 1(I), alpha 1(III), and
      alpha 1(IV) transcription was focal, spatially related but temporally ordered.
      Collagen I, III, and IV immunostaining was increased from days 3, 24, and 100,
      respectively (P < 0.05 versus day 0 and day 100 saline). However, when corrected
      for glomerular density, collagen I immunostaining decreased between days 24 and
      100, whereas collagen III and IV no longer differed from day 0. MMP staining
      within the lesion was confined to occasional interstitial and epithelial cells
      throughout. It is concluded that in this model, contraction and collapse of the
      tubulointerstitial parenchyma has a greater influence than new collagen
      production on final fibrotic density.

PMID- 9555667
TI  - Exogenous norepinephrine induces an enhanced microproteinuric response in
      microalbuminuric insulin-dependent diabetes mellitus.
AB  - Exogenous norepinephrine (NE) increases intraglomerular pressure in animal
      experiments, but it is unknown whether NE induces a microproteinuric response in
      humans. Moreover, it has not been studied whether possible microproteinuric and
      renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes
      mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric
      and renal hemodynamic responses to exogenous NE infusions were measured in eight
      matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients
      (group D2), and control subjects (group C). As anticipated, mean arterial
      pressure (MAP)-NE dose-response curves were significantly shifted leftward in
      groups D1 and D2 compared with group C (P < 0.05), indicating a higher systemic
      NE responsiveness in IDDM. On separate days, NE or placebo was infused at
      individually determined NE threshold doses (T; delta MAP = 0 mmHg), 20% pressor
      doses (20% P; delta MAP = 4 mmHg), and pressor doses (P; delta MAP = 20 mmHg),
      with measurement of urinary albumin (UalbV), IgG excretion (UIgGV), GFR (by 125I
      iothalamate), and effective renal plasma flow (by 131I-hippurate). At NE pressor
      dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), whereas urinary beta
      2-microglobulin was unchanged. The increases in UalbV and UIgGV were more
      pronounced in the microalbuminuric group than in the other groups (P < 0.05). An
      NE dose-dependent fall in effective renal plasma flow and rise in filtration
      fraction were found in all groups (P < 0.05 to 0.001 for all), whereas GFR did
      not change significantly. The renal hemodynamic dose-response relationship was
      similar in the groups. In conclusion, exogenous NE acutely promotes glomerular
      protein leakage, and it is plausible that intraglomerular NE effects contribute
      to this phenomenon. The microproteinuric response is enhanced in microalbuminuric
      IDDM despite unaltered renal hemodynamic responsiveness, which may reflect a
      specific NE response or a general effect of vasopressor stimuli to promote
      glomerular protein leakage in patients with a preexistent defect in glomerular
      permselectivity.

PMID- 9555668
TI  - Neutrophil impairment associated with iron therapy in hemodialysis patients with
      functional iron deficiency.
AB  - Hemodialysis patients treated with recombinant human erythropoietin (rhEPO) need
      adequate iron supplementation to avoid rhEPO hyporesponsiveness due to iron
      deficiency. Low serum ferritin reflects absolute iron deficiency, whereas normal
      or high ferritin values in combination with low transferrin saturation (< 20%)
      indicate functional iron deficiency. In this study, healthy subjects (group I)
      were compared with intravenous (i.v.) rhEPO-treated and i.v. iron-saccharate
      treated regular hemodialysis patients that were subdivided into three groups as
      follows: patients with serum ferritin > 100 and < 350 micrograms/L (group II),
      patients with ferritin < 60 micrograms/L (group III), and patients with ferritin
      > 650 micrograms/L but transferrin saturation < 20% (group IV). Polymorphonuclear
      leukocyte (PMNL) parameters (phagocytosis, intracellular killing of bacteria,
      oxidative metabolism, glucose uptake, intracellular calcium) for each group were
      compared with those of multitransfused, iron-overloaded primary hematologic
      patients (group V) and those of patients suffering from hereditary
      hemochromatosis (group VI). Compared with PMNL obtained from healthy subjects
      (group I), group II hemodialysis patients showed mild inhibition of phagocytosis
      but significant inhibition of intracellular killing of bacteria. Oxidative burst
      of PMNL from group II patients was also significantly reduced after stimulation
      in vitro. These dysfunctions were not affected by absolute iron deficiency
      (comparable data in group III patients). However, impairment of PMNL was markedly
      aggravated in group IV patients. Intracellular calcium concentration under basal
      conditions and after stimulation was not different. These data suggest that iron
      is responsible for the PMNL dysfunctions observed in group IV patients. The PMNL
      defect of group IV patients was comparable to group V and group VI patients with
      normal renal function, suggesting again a direct inhibitory effect of iron. It is
      concluded that hemodialysis patients with high ferritin but low serum iron and
      low transferrin saturation ("functional iron deficiency") display a significant
      impairment of fundamental PMNL functions during i.v. iron and rhEPO therapy. This
      may result in increased risk of infectious complications. Therefore,
      overtreatment of hemodialysis patients with i.v. iron should be avoided.

PMID- 9555669
TI  - Intravenous infusion of total dose iron is superior to oral iron in treatment of
      anemia in peritoneal dialysis patients: a single center comparative study.
AB  - In the treatment of anemia of chronic renal failure, the most common cause of
      recombinant human erythropoietin (rhEPO) resistance is iron deficiency. In
      peritoneal dialysis (PD) patients, oral iron therapy is an accepted and
      convenient method of iron supplementation. The effectiveness of oral iron,
      however, is limited by many factors, including gastrointestinal side effects and
      poor gastric absorption. This study prospectively compared the efficacy of single
      intravenous infusion of total dose iron (ITDI group) given in an outpatient
      setting with oral iron (oral group) for the treatment of anemia in PD patients.
      Twenty-five adult stable PD patients with baseline hematocrit 25 to 35% were
      entered into the study. Thirteen patients with serum transferrin saturation
      (TSAT) < 25% received ITDI, and 12 patients with TSAT between 25 and 35% received
      oral iron. One patient in the oral group received emergent blood transfusion and
      was excluded from analysis. Hematocrit and iron indices were measured at monthly
      intervals. Doses of rhEPO were adjusted monthly to maintain target hematocrit at
      35%. At the end of the study (6 mo), despite similar baseline mean hematocrit
      (31.0 +/- 0.9 versus 33.0 +/- 1.0%), comparable mean baseline weekly rhEPO dose
      (7886 +/- 1449 versus 6370 +/- 1553 U/wk), and significantly lower level of mean
      TSAT (11.3 +/- 3.5 versus 30.1 +/- 3.5%; P < 0.05), the ITDI group when compared
      with the oral group had significantly higher mean hematocrit (36.0 +/- 1.0 versus
      31.4 +/- 1.1%; P < 0.05) and TSAT (33.7 +/- 3.7 versus 22.6 +/- 4.0%; P < 0.05)
      values. In addition, the final mean dose of weekly rhEPO was significantly lower
      in the ITDI group (4799 +/- 981 versus 9998 +/- 1027 U/wk; P < 0.05). No patient
      in the ITDI group developed an adverse reaction to intravenous iron. It is
      concluded that ITDI represents a more efficacious method of iron supplementation
      in PD patients receiving rhEPO. Moreover, ITDI is safe and well tolerated and can
      be administered in an outpatient setting.

PMID- 9555670
TI  - New strategies to prevent Staphylococcus aureus infections in peritoneal dialysis
      patients.
AB  - The importance of Staphylococcus aureus as etiological agent for catheter-related
      infections and peritonitis in peritoneal dialysis patients is well established.
      To evaluate groups at risk of developing Staphylococcus aureus infections, nasal
      and exit-site cultures were performed in 76 peritoneal dialysis patients monthly
      over a period of 3 yr. The risk of Staphylococcus aureus catheter infection was
      significantly higher in diabetic (group 1) and immunosuppressed (group 2)
      patients compared with nondiabetic and nonimmunosuppressed (group 3) patients. In
      diabetic patients, Staphylococcus aureus-positive nasal cultures were more
      frequent than positive cultures taken from the bland exit-site (73.3% versus
      60.0%). On the other hand, both positive and negative exit-site cultures had a
      better prognostic value for Staphylococcus aureus catheter infection compared
      with nasal cultures. In immunosuppressed patients, both nasal and exit-site
      carriages were associated with a very high risk of Staphylococcus aureus catheter
      infection, but nasal swabs were far more often positive than swabs from the bland
      exit-site (72.7% versus 25.0%). However, the risk of infection was also high for
      non-nasal and non-exit-site carriers in this group. In nondiabetic and
      nonimmunosuppressed patients, the risk of Staphylococcus aureus catheter
      infection was increased only if two or more positive nasal cultures were
      detected. It is concluded that in diabetic patients, antibiotic prophylaxis
      should be performed in all Staphylococcus aureus exit-site carriers. All
      immunosuppressed patients should be treated prophylactically. In contrast, in
      nondiabetic and nonimmunosuppressed patients, prophylactic treatment should be
      considered only in nasal carriers with two or more positive cultures. The overall
      low peritonitis rate does not influence this prevention strategy.

PMID- 9555671
TI  - Analysis of fracture prevalence in kidney-pancreas allograft recipients.
AB  - Fractures occur in 11 to 26% of renal allograft recipients after transplantation
      despite improvements in bone and mineral disorders. This high fracture rate is
      likely a consequence of accelerated osteopenia. The cause of posttransplant bone
      loss is multifactorial, and patients with insulin-dependent diabetes mellitus and
      renal failure may have additional fracture risks such as low turnover bone
      disease. This retrospective cohort study was undertaken to determine the long
      term incidence and the potential risk factors of posttransplant fractures in
      patients with insulin-dependent diabetes mellitus undergoing combined kidney
      pancreas allograft transplantation. Thirty-five patients with insulin-dependent
      diabetes mellitus who received a combined kidney-pancreas allograft between 1987
      and 1992 were evaluated. Thirty-five kidney allograft recipients matched for age,
      gender, and the date of transplant were also reviewed. The fracture incidence in
      the kidney-pancreas group was 49% after transplantation. The rate of first
      fracture after kidney-pancreas transplantation was 12.1% per patient year,
      resulting in a 5-yr fracture-free rate of 48%. The initial fracture occurred at a
      mean of 31.06 +/- 19.9 mo. Steroid exposure was found to increase the risk of
      fracture, and analysis by means of a Cox regression model estimated that an
      increase in cumulative steroid exposure of 10 mg/kg at any given month increased
      the hazard of sustaining a fracture by 9% (95% confidence interval for hazard
      ratio, 1.01 to 1.18; P = 0.031). This analysis suggests that kidney-pancreas
      recipients are at significant risk of sustaining a fracture within a few years
      after transplantation.

PMID- 9555672
TI  - Predictors of mortality and the provision of dialysis in patients with acute
      tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group.
AB  - To explore the natural history of critically ill patients with acute renal
      failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the
      placebo arm of a randomized clinical trial. Death and the composite outcome,
      death or the provision of dialysis, were determined with follow-up to 60 d. The
      relative risks (RR) and 95% confidence intervals (95% CI) associated with
      routinely available demographic, clinical, and laboratory variables were
      estimated using proportional hazards regression. Ninety-three (36%) deaths were
      documented; an additional 52 (20%) patients who survived received dialysis.
      Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36),
      oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95%
      CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31),
      acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic
      immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06;
      95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic
      acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum
      bicarbonate concentration). Predictors of death or the provision of dialysis were
      oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95%
      CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07),
      arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95%
      CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither
      mortality nor the provision of dialysis was related to patient age. These
      observations can be used to estimate risk early in the course of acute tubular
      necrosis. Furthermore, these and related models may be used to adjust for case
      mix variation in quality improvement efforts, and to objectively stratify
      patients in future intervention trials aimed at favorably altering the course of
      hospital-acquired acute renal failure.

PMID- 9555673
TI  - The aging kidney: insights from experimental studies.
AB  - The rat provides a useful experimental model to study of the mechanisms of kidney
      aging. As in man, a wide diversity in the renal response to aging occurs in the
      rat, and because of this variability it is important to always specify
      experimental conditions, i.e., strain, gender, diet, and environment. Most aging
      rats display chronic progressive nephrosis, although the rate at which injury
      develops is highly variable. There are a number of known risk factors that
      potentiate injury, including male gender, genetic background, obesity, high
      protein/high calorie diet, and environmental exposure to pathogens. The causes of
      age-dependent glomerulopathy are multifactorial and include an imbalance between
      synthesis and degradation of extracellular matrix products, as well as
      hemodynamic alterations. Of importance, this damage is not inevitable and can be
      dissociated from normal kidney aging when optimal conditions for successful aging
      are provided. There is complex and sometimes contradictory information on
      vasoactive factors. It is, likely, however, that the activity of intrarenal AngII
      is somehow upregulated in the aging kidney of some, but not all, strains, and
      alpha 1-dependent renal nerve activity may also be enhanced. The endothelial
      vasodialtory prostaglandins and NO exert an increasingly important role in the
      maintenance of renal perfusion with advancing age, although their production may
      be diminished. In the future, we anticipate that comparison of rats with
      different genetic backgrounds will help to dissociate true aging from disease.

PMID- 9555674
TI  - Hospital-acquired acute renal failure.

PMID- 9555676
TI  - Women, wine, and information whiplash.

PMID- 9555675
TI  - The treatment of chronic uremia by means of intermittent hemodialysis: a
      preliminary report. 1960.

PMID- 9555677
TI  - Sexual addiction: a new phenomenon?. Interview by J.G. Meisler.

PMID- 9555678
TI  - All's fair ... but not in diabetes women's unique vulnerability: Part I.

PMID- 9555679
TI  - Choices: biomedical ethics and women's health. Ethical issues and dilemmas.

PMID- 9555680
TI  - Nutriceutical review of St. John's wort (Hypericum perforatum) for the treatment
      of depression.

PMID- 9555681
TI  - Obesity is no laughing matter.

PMID- 9555682
TI  - The role of weight loss drugs in the treatment of obesity in women.

PMID- 9555684
TI  - Preventing coronary disease in women: brief observations from the clinical data.

PMID- 9555683
TI  - The special prenatal clinic: one approach to women and substance abuse.
AB  - We aimed to determine if the trend in substance use in this central core of a
      large inner-city area confirmed an increase in marijuana use among young women <
      22 years of age as childbearing years were beginning or if marijuana use and
      harder drug use were greatest among women beyond the teens and the early second
      decade of life and to describe one prenatal care intervention. Statistical
      reports for the Special Prenatal Clinic, a Harlem clinic for women with a current
      or past history of substance use, were reviewed from 1985 (the clinic's
      inception) through March 1996 to determine the trends, patterns, and types of
      drug use. Findings chronicled the beginning and rise in crack cocaine use,
      especially after 1986, confirmed an increase in marijuana use by adolescents
      since 1992, and suggest that the risk for use of hard drugs increases with age,
      predominantly in the childbearing years. Intervention by the Special Prenatal
      Clinic aided case-finding, allowed for comprehensive care, offered women
      opportunities for behavior change, and increased their chances of keeping their
      babies after delivery.

PMID- 9555685
TI  - Cardiovascular disease in women: gender-specific aspects of hypertension and the
      consequences of treatment.
AB  - The epidemiology, clinical course, response to treatment, and ultimate outcome of
      essential hypertension vary as a function of gender. Three early trials on
      hypertension reported an increase in all-cause mortality in treated white women
      compared with black women or with men of both races. Later studies, however,
      suggest that drug therapy has similar and beneficial effects in hypertensive men
      and women. Women may tolerate hypertension better than do men. Diastolic
      hypertension correlates with higher mortality from coronary artery disease in men
      than in women. Special considerations apply to treating the hypertensive woman.
      Use of oral contraceptives may precipitate or accentuate the problem. In
      contrast, in the postmenopausal female, estrogen replacement may actually improve
      hypertension, via several mechanisms. These include the impact of the hormone on
      vasomotricity, its enhancement of baroreceptor sensitivity, and its impact on the
      hyperinsulinemia characteristic of menopause. Treatment of hypertension must be
      individualized with respect to gender. More data on the consequences of treatment
      of women with hypertension are needed, particularly longterm studies to assess
      the impact of treatment on mortality.

PMID- 9555686
TI  - Bulimia: a primary care approach.
AB  - More common than anorexia and less easily detected, bulimia typically begins as
      an effort to control weight. Although the prognosis is better than that for
      anorexia nervosa, a number of medical complications can arise related to the mode
      of purging. Some of these complications can have profound deleterious sequelae if
      not diagnosed and treated.

PMID- 9555687
TI  - Prior oral contraceptive use is associated with higher blood pressure in older
      women.
AB  - Studies of young, premenopausal women suggest that changes in coronary risk
      factors do not persist after discontinuation of oral contraceptive use. However,
      little is known about longterm effects of past oral contraceptive use in older,
      postmenopausal women, who typically have a more atherogenic profile. This study
      examines the relation of past oral contraceptive use (including duration) to
      heart disease risk factors in postmenopausal women. Subjects were 517 women aged
      50-69 from the Rancho Bernardo Study who attended follow-up clinic visits. Past
      oral contraceptive use was reported by 24.2% and two thirds had used oral
      contraceptives < or = 5 years. After adjustment for covariates, the only
      significant difference was that past users had higher diastolic blood pressures
      than never users (p < 0.01). Among older women, the diastolic blood pressure of
      past users was 3.9 mm Hg higher than that of never users (p < 0.01). Women who
      used oral contraceptives for < or = 5 years had diastolic blood pressures 3.6 mm
      Hg higher than those of never users (p < 0.01). No differences were found among
      younger women or those who used oral contraceptives > or = 6 years. Past oral
      contraceptive users may be at increased risk for heart disease because of a small
      but significant elevation in diastolic blood pressure that persists many years
      after discontinuing oral contraceptive use.

PMID- 9555688
TI  - Predicting anonymous egg donor satisfaction: a preliminary study.
AB  - Our aim was to assess the psychologic characteristics and postdonation
      satisfaction of anonymous oocyte donors. Twenty-five consecutive anonymous oocyte
      donors completed psychologic tests before donation and satisfaction ratings
      following completion of the egg donation cycle. The average donor was 27 years
      old, married, and employed outside the home. All predonation scores on the
      psychologic measures were within the normal range. However, 24% of donors
      reported a history of sexual assault, and 40% described having had some type of
      reproductive loss. Although monetary compensation for donation was provided,
      altruism was reported as the most salient motivating factor. Following oocyte
      donation, 80% of women stated that they would be willing to donate again.
      Postdonation satisfaction was high. A significant negative correlation was found
      between predonation financial motivation and postdonation satisfaction (r = -.48,
      p < 0.01) and between predonation ambivalence and postdonation satisfaction (r = 
      .84, p < 0.0001). Donors with high levels of predonation financial motivation or
      ambivalence should be carefully screened and counseled before oocyte donation to
      ensure satisfactory psychologic outcome.

PMID- 9555689
TI  - Predictors of mammography use among women veterans.
AB  - We examined mammography use patterns of women veterans and explored Veterans
      Administration (VA) health care use and military experience as predictors of
      mammography use by this population. We conducted a national telephone survey of
      women veterans. A sample of 397 women veterans was selected from all military
      discharges from 1971 through 1994. A 3 x 2 stratification scheme was used: three
      age groups (35-49, 50-64, > or = 65 years old) and two VA user groups indicating
      whether (VA user) or not (VA nonuser) they received any health care from a VA
      Medical Center in the last 5 years. The response rate was 75% (297 of 397).
      Analyses included bivariate techniques and weighted logistic regression. We found
      that women veterans told to have a mammogram by a health care professional were
      more than five times more likely to have ever had a mammogram (OR 5.41, CI 4.63
      6.32) and nearly twice as likely to have had a mammogram within the past 2 years
      (OR 1.81, CI 1.57-2.09) as those who were not told to do so, controlling for age,
      race, VA user status, and length of military service. Regular VA users were more
      likely to have had a mammogram ever and within the past 2 years, controlling for
      other factors. Mammography use was not necessarily at a VA medical center.
      Interventions that promote better provider-patient communication and target older
      women veterans may have the most potential benefit. Whether VA health care is
      filling an important gap in access to mammography for older women veterans is an
      important policy question and warrants further research.

PMID- 9555690
TI  - Changes in sick leave rates and the use of pregnancy-associated social benefits
      among pregnant Swedish women: an outcomes study.
AB  - We attempted to determine if an amended social security system has lessened the
      rate of sickness absence during pregnancy in Sweden over the period 1978-1989. We
      studied the records of 3998 women who gave birth in 1978, 1986, 1988, and 1989 at
      the University Hospital in Linkoping and the Varnamo County Hospital.
      Retrospective collection of all data concerning the rates and durations of
      sickness absence during pregnancy, drawing of parental benefit, and use of
      granted pregnancy benefit was performed from Sweden's standardized social
      security files. Obstetric variables concerning the course and outcome of
      pregnancy and delivery, as well as the health status of the newborns, were
      obtained from standardized and antenatal care and delivery files. Between 1978
      and 1989, the rate of sickness absenteeism during pregnancy increased by almost
      100% for periods of absence not supported by a doctor's certificate and by about
      50% for those with a doctor's certificate. During the same time, the average
      number of days of sick leave per pregnant woman more than doubled. The changes
      were most apparent among younger pregnant women. During the decade studied, no
      significant differences were found with regard to antenatal care, modes of
      delivery, or the health status of the newborns. In spite of the introduction
      within the Swedish social security system of more generous rules for pregnant
      women, the changes in the rates of registered sick leave during pregnancy
      observed over time were most unfavorable. The present study indicates that the
      rate of sick leave during pregnancy reflects a complex social phenomenon and
      cannot be explained solely by an increase in the rate of actual illness or
      sickness. Such a rate is also likely to depend on general attitudes and
      expectations among pregnant women, which may vary over time. When amendments in
      social benefits for pregnant women are considered to improve the health status of
      the pregnant population, society ought to clearly define the precise aim pursued
      and the consequences expected to escape unintended socioeconomic results.

PMID- 9555691
TI  - Bilaterality and recurrence rates for lobular breast cancer: considerations for
      treatment. Ann Surg Oncol 1997;4(3):198-202.

PMID- 9555692
TI  - Neonatal outcome in women treated for the antiphospholipid syndrome during
      pregnancy. J Perinat Med 1997;25(2):192-196.

PMID- 9555693
TI  - National treatment trends for ductal carcinoma in situ of the breast. Arch Surg
      1997 Jun;132:660-665.

PMID- 9555694
TI  - Analysis of long-term Elmiron therapy for interstitial cystitis. Urology
      1997;49(Suppl 5A):93-99.

PMID- 9555695
TI  - Brachytherapy and breast cancer. Semin Surg Oncol 1997;13:190-195.

PMID- 9555696
TI  - Literature Watch.

PMID- 9555697
TI  - [Postoperative results of stapes revision].
AB  - BACKGROUND: In this retrospective study indications, intraoperative findings,
      reconstruction techniques and postoperative hearing results in revision stapes
      surgery were evaluated. PATIENTS: Between March 1988 and January 1996, 150
      patients underwent stapes revision. Indications for surgery were the presence of
      conductive hearing loss (132), dizziness (12), sensorineural hearing loss (3),
      deafness (2), and tinnitus (1). RESULTS: Intraoperative findings were lateral
      migration of the implant, regrowth of bone in the oval window niche, erosion of
      incus, cholesteatoma, and others. In most cases a new prosthesis (gold piston)
      was inserted between incus and vestibulum. In cases with incus erosion, a
      malleovestibulopexy was performed. Seventy-three percent of patients who
      underwent revision stapes surgery because of conductive hearing loss showed a
      hearing improvement of 20 dB or more. All patients who underwent revision stapes
      surgery because of dizziness reported an improvement of their symptoms
      postoperatively. CONCLUSIONS: Revision stapes surgery should be approached by
      experienced surgeons, because the risk of severe sensorineural hearing loss is
      higher than at the time of primary stapedectomy. Informed consent is mandatory.

PMID- 9555698
TI  - [Fixation of the temporarily removed posterior wall of the auditory canal with
      plate osteosynthesis: a new technique].
AB  - BACKGROUND: Temporary removal of the posterior external ear canal wall allows
      excellent exposure of the middle ear and epitympanum without the negative
      sequelae of a cavity as can occur after canal-wall down procedures. Safe fixation
      of the bony canal wall, however, has not always been possible with a risk for
      prolonged healing and bone necrosis. MATERIAL AND METHODS: A new technique
      permits rigid internal fixation of the posterior canal wall. A titanium miniplate
      of 10 holes length commonly used for orbital rim surgery is adapted to the
      cortical surface of the mastoid just posterior to the external ear canal. Six
      holes for 1.3 mm screws are drilled into the cortical bone: two screws behind the
      ear canal, two screws on the temporal line, and two on the mastoid tip. All
      fixation material is then removed and a mastoidectomy is carried out with
      preservation of the cortical bone for the screws. The external ear canal skin,
      which has been incised previously near the fibrous annulus with lateral
      extensions, is mobilized laterally using a newly designed retroflected
      microraspatory. This creates a vital skin flap that might be essential to avoid
      bone necrosis. No other skin incisions are needed in the canal. The posterior
      bony canal wall is cut using an oscillating saw Osseoscalpel, secured by facial
      nerve monitoring. After middle ear surgery and tympanoplasty have been completed,
      the canal wall is repositioned and fastened precisely in its place with rigid
      internal fixation allowing a secure stabilization. RESULTS: This new technique
      has proven to be safe and reliable on the first five patients. There has been no
      bone necrosis within an observation period of 18 months. CONCLUSIONS: Rigid
      internal fixation is an alternative technique to safely readapt the posterior
      auditory canal wall.

PMID- 9555699
TI  - [Functional long-term results after open cholesteatoma surgery and ossiculoplasty
      with allogenic ossicles in adulthood].
AB  - BACKGROUND: Characteristic features of cholesteatoma of the middle ear are
      destruction of the bone and a high tendency for recurrent disease. The choice of
      surgical procedure is determined by audiological results and the rate of
      recurrent cholesteatoma. PATIENTS: One hundred fifty patients who underwent
      primary cholesteatoma surgery were investigated 3-5 years postoperatively.
      Preoperative and postoperative audiological results and rate of revision surgery
      were compared for the respective surgical procedures. All cholesteatomas were
      treated with an open surgical technique. The lateral attic walls and
      cholesteatomas were removed. RESULTS: Cholesteotoma recurred in 15 patients
      (10%). Primary reconstruction of the ossicular chain with a tympanoplasty (type
      III) was performed in 98 patients in the first operation. Approximately 80% of
      patients treated with a type III tympanoplasty had a maximum postoperative air
      bone gap of 20 dB in the main speech range, depending on the frequency. In about
      50% of patients, this value was 10 dB or less. Comparison of preoperative and
      postoperative conductive hearing loss between 250 Hz and 8000 Hz revealed an
      improvement (p < 0.05) of 10 dB (500 Hz, 3000 Hz, 4000 Hz) and 15 dB (250 Hz,
      1500 Hz, 2000 Hz, 8000 Hz). CONCLUSIONS: In our opinion, a second look operation
      should be performed in cases where a large cholesteatoma cannot be removed with
      sufficient reliability. This applies especially to a cholesteatoma in the oval
      window. Here, we suggest second-look surgery after one year.

PMID- 9555700
TI  - [Hearing loss caused by high dose carboplatin therapy].
AB  - BACKGROUND: Carboplatin is regarded as a non-ototoxic or low-grade ototoxic
      chemotherapeutic agent. METHOD: We report on three patients with a recurrence of
      testicular cancer after cisplatin chemotherapy who suffered hearing loss after
      subsequent high-dose carboplatin therapy. RESULTS: Audiometry demonstrated
      carboplatin-induced hearing loss primarily in the mid-range and high frequencies
      up to 45 dB at 3 kHz and up to 55 dB at 8 kHz. In two of three patients,
      transitory-evoked otoacoustic emissions were absent after carboplatin therapy.
      CONCLUSION: Following first-line cisplatin chemotherapy, salvage treatment with
      high-dose carboplatin can generate hearing loss in the middle and high
      frequencies.

PMID- 9555702
TI  - [Voice rehabilitation after total laryngectomy. Voice prostheses or esophageal
      replacement voice?].
AB  - BACKGROUND: During the last years tracheoesophageal fistula has a well
      established role and in several units is now the principal means of speech
      rehabilitation following laryngectomy. The purpose of this study is to present
      the long term results after using the Provox voice prosthesis and to compare the
      phonetic results obtained with this means of speech rehabilitation with
      esophageal speech. PATIENTS, METHODS, AND RESULTS: During the last 7 years, 265
      laryngectomy patients were trained in our Department in an effort to develop
      esophageal speech. One hundred and twelve of them developed comprehensive speech
      of various quality. In another group consisting of 35 patients, a Provox low
      resistance, self-retaining prosthesis was fitted. Twenty-nine of them developed a
      very good voice. Ten patients of each group were tested in order to estimate the
      quality of voice of the two methods. Three measurements were obtained from each
      patient: the maximal intensity, the maximal phonation time, and the number of
      syllables with one breath. CONCLUSION: All the results confirmed the better
      quality of the tracheo-esophageal speech. The main two advantages of the
      prosthesis are the effortless speech due to the low resistance of the valve and
      the simple maintenance by the patient. The most important disadvantage is the
      cost and the need to occlude the stoma during phonation. Conclusively each method
      of speech rehabilitation should be selected individually according to the needs,
      desire, and abilities of every patient.

PMID- 9555701
TI  - [Hypopharyngeal carcinomas and radical operation--can one refrain from total
      laryngeal excision?].
AB  - BACKGROUND: Patients with hypopharyngeal carcinoma have a poor prognosis. In
      reviewing patients treated at our clinic from 1977 to 1990, we wanted to find out
      how this prognosis is influenced by the degree of surgical radicality (total vs.
      partial laryngectomy). METHODS: From 1984 to 1990, 46 patients with carcinoma of
      the hypopharynx were treated at the ENT department of ZKH St.-Jurgen-Strasse in
      Bremen and followed up for 5 years. All patients had been treated by radiotherapy
      and all, except 3 patients, had had additional surgery of the lymph nodes. In 14
      patients the primary tumor had been only irradiated (group 1), and in 32 patients
      it had been removed by surgery (groups 2 and 3). Surgical removal of the primary
      tumor had been combined with partial resection of the hypopharynx and of the
      larynx only (group 2) or with total laryngectomy (group 3). There were no
      differences in tumor stages between groups 1 and 3, which comprised mainly stages
      III and IV. Stages I and II were overrepresented in group 2. RESULTS: The 5-year
      survival rate was 37% for all patients, and for groups 1, 2 + 3, 2 and 3, 31%,
      40%, 58%, and 28%, respectively. DISCUSSION: These results are superior to those
      obtained between 1977 and 1983 for 49 patients who had been treated either by
      excision of the primary tumor combined with laryngectomy, or by irradiation
      alone, without neck dissection. The respective 5-year survival rates were 19% for
      all patients, 11% for the group of radiotherapy alone, and 33% for patients
      undergoing additional surgery. CONCLUSION: In our opinion less radical surgical
      procedures are justified for the treatment of hypopharyngeal cancer.

PMID- 9555703
TI  - [Long-term functional outcome of Laccourreye hemipharyngectomy-hemilaryngectomy
      with reference to oncologic outcome].
AB  - BACKGROUND: Various techniques for the treatment of hypopharyngeal malignancies
      are used to achieve disease control while preserving laryngeal function. PATIENTS
      AND METHODS: This study details the long-term results of 22 patients (ages 39-80;
      average age 57 years) following hemipharyngo-hemilaryngectomy (described by
      Laccourreye) for unilateral hypopharyngeal squamous cell carcinomas (G2-G3; T1
      T4; N0-N3). Follow-up was 16-83 months (average 43) and included extensive speech
      and swallowing assessment. From 1989-1994 the procedure was performed in 26
      patients. Two died within one year postoperatively, two were lost for follow-up,
      and 22 were included in this study. RESULTS: One patient developed recurrent
      disease with liver metastasis; two patients were successfully treated for
      recurrent disease. Two patients developed second primary tumors, while all others
      had no signs of recurrent disease. Fourteen patients had no difficulties eating
      or drinking. Six patients could only eat soft foods, and two patients required a
      gastrostomy feeding tube. Nineteen patients had a useful but hoarse voice, and
      three patients had severe difficulties when communicating. Modulation of voice
      was decreased because the supraglottic structures (mainly false cord and scar
      tissue) were used for phonation. Eighteen patients were completely satisfied with
      their voice. The tracheotomy was closed in 18 patients within six months, while
      four patients required a tracheostoma for more than two years. CONCLUSIONS: These
      data show that function-preserving surgical techniques can be successfully used
      in hypopharyngeal carcinomas even for patients with advanced disease. Useful
      functional results for swallowing, voice, and airway were achieved in most
      patients undergoing this procedure.

PMID- 9555704
TI  - [Epistaxis strategy--experiences with the last 360 hospitalizations].
AB  - BACKGROUND: The purpose of this study was to analyze the therapy concept used in
      the management of severe epistaxis in order to optimize the quality of our
      treatment and to arrive at an optimal therapeutic concept. MATERIAL AND METHODS:
      The study was performed as a retrospective analysis of the charts of all 335
      patients treated as inpatients for epistaxis over a period of 6 years. RESULTS:
      An increased rate of complications was found in the following three situations:
      1. Age > 65 years, 2. chronic obstructive pulmonary disease, 3. several systemic
      illnesses. Recurrence was increased with septal perforations and Osler's disease.
      CONCLUSIONS: Localization of the site of bleeding is the first priority and
      allows treatment of bleeding with bipolar electrocautery. If the bleeding vessel
      is not found, insertion of a Merocel pack is recommended. Patients with
      persistent or recurrent bleeding are treated in the operating theater under
      general anesthesia if they are at an elevated risk for complications or have a
      septal deviation which is clinically significant. The nose is systematically
      visualized with the endoscope, bleeding vessels are coagulated under endoscopic
      control, and, where appropriate, a septoplasty is performed. In the remaining
      cases an epipharynx balloon is inserted, combined with an anterior pack.
      Angiography with superselective embolization, external ligation of the ethmoidal
      arteries, and endonasal obliteration of the sphenopalatine artery is reserved for
      cases where the measures discussed above have failed.

PMID- 9555705
TI  - [Arachnoid cyst of the sphenoid sinus].
AB  - BACKGROUND: Arachnoid cysts of the paranasal sinus are rare. They have not been
      described yet in the sphenoid sinus. PATIENT AND METHOD: Microscopic-endoscopic
      endonasal surgery of the sphenoid sinus was performed on a 34-year-old female
      with a history of chronic headaches and a suspected mucocele of the sphenoid
      sinus in computed tomography (CT) and magnetic resonance imaging (MRI) studies.
      An extended arachnoid cyst was found in the enlarged sphenoid sinus, which was
      obliterated with collagen, fibrin glue, and abdominal fat. RESULTS: There were no
      complications after the operation, and 12 months later the patient is still free
      of symptoms. CONCLUSION: Arachnoidal cysts present in CT and MRI as fluid dense
      lesions that can imitate a mucocele.

PMID- 9555706
TI  - [Macrolide antibiotic-induced vasculitis (Churg-Strauss syndrome)].
AB  - BACKGROUND: Macrolides are known to have relatively few side effects and are
      prescribed in cases of allergic reaction to penicillin. The new macrolides, for
      example Azithromycin and Roxithromycin, are increasingly preferred over
      erythromycin at the ear, nose, and throat out-patient department due to improved
      oral reabsorption (acid resistance), better penetration into tissue, prolonged
      half-life, extended antibacterial activity, modest side effects, and better
      pharmacokinetics. There are only few case reports concerning side effects of
      macrolides. We report on the appearance of a Churg Strauss-Syndrome (CSS) in a
      patient following intake of the macrolide antibiotic azithromycin and
      roxithromycin. PATIENT: A 50-year-old patient with asthma for three years
      presented with arthritis and mononeuritis multiplex. Laboratory and radiological
      investigations revealed eosinophilia (64%), eosinophilic infiltrations of bone
      marrow, raised IgE-level, and transient pulmonary infiltrates. THERAPY AND
      DEVELOPMENT: Intravenous steroid therapy was started and resulted in
      normalization of eosinophilia, IgE-level, and asthmatic symptoms. The neurologic
      deficits showed only a weak tendency for improvement. CONCLUSION: The diagnosis
      of CSS was established on the basis of clinical criterias and laboratory
      investigations. The diagnosis was supported by the fact that a similar course of
      the disease was observed one year ago following administration of azithromycin,
      another macrolide.

PMID- 9555707
TI  - [Isolated paralysis of the ramus marginalis mandibulae nervi facialis: clinical
      aspects, etiology, diagnosis and therapy. An overview].
AB  - BACKGROUND: Disorders of lower lip in facial expression are mostly caused by
      functional impairment of the marginal mandibular branch of the facial nerve. In a
      typical case, active exposure of the incisors of the mandible is not possible and
      the lip appears distorted towards the healthy side. The most frequent cause of a
      lesion of the marginal mandibular branch is iatrogenic injury during operations
      in the mandibular or parotid region. DIFFERENTIAL DIAGNOSIS: Functional disorders
      of the platysma, congenital hypoplasia or aplasia of the lower lip muscles, and
      defective healing following facial palsy may lead to a similar disorder which,
      however, must be differentiated from an isolated paralysis of the marginal
      mandibular branch. TREATMENT: In addition to inactivation of the nerve branch on
      the opposite side, several surgical procedures have been described to achieve not
      only aesthetic, but also functional rehabilitation of lower lip expression. The
      present review gives an overview on the causes, clinical appearance, diagnosis,
      differential diagnosis, and therapy of unilateral isolated paresis of the
      marginal mandibular branch of the facial nerve.

PMID- 9555708
TI  - Monitoring protocols for biological weapons.

PMID- 9555709
TI  - A shot in the arm for DNA vaccines.

PMID- 9555710
TI  - The Biological Weapons Convention and the biopharmaceutical industry: the views
      of the United Kingdom.

PMID- 9555711
TI  - The emerging role of the genomics revolution in agricultural biotechnology.

PMID- 9555712
TI  - In hot pursuit of extremophiles.

PMID- 9555713
TI  - The engineering of drug discovery.

PMID- 9555714
TI  - Remune response.

PMID- 9555715
TI  - Furry flasks?

PMID- 9555716
TI  - Pharming cloning ban could spread.

PMID- 9555717
TI  - Detecting drug-resistant tuberculosis: beacons in the dark.

PMID- 9555718
TI  - PNA, antisense, and antimicrobials.

PMID- 9555719
TI  - Containing excitement over transplastomic plants.

PMID- 9555720
TI  - WAPping gastroenteritis with transgenic antibodies.

PMID- 9555721
TI  - Transfected human dendritic cells as cancer vaccines.

PMID- 9555722
TI  - Mining the genetic riches of human populations.

PMID- 9555723
TI  - Therapeutic repair of mutated nucleic acid sequences.
AB  - The principle of therapeutic nucleic acid repair has been demonstrated in cell
      free and cell culture experiments, in which compounds bind to and repair mutated
      sequences, thereby treating the primary defects of genetic disease. The
      mechanisms used to promote repair are diverse, encompassing techniques related to
      antisense, triple-strand, and ribozymes. Therapeutic nucleic acid repair has the
      potential to revert mutations to wild type, and therefore is more suitable than
      traditional gene therapy for treating gain-of-function mutations.

PMID- 9555724
TI  - Containment of herbicide resistance through genetic engineering of the
      chloroplast genome.
AB  - Glyphosate is a potent herbicide. It works by competitive inhibition of the
      enzyme 5-enol-pyruvyl shikimate-3-phosphate synthase (EPSPS), which catalyzes an
      essential step in the aromatic amino acid biosynthetic pathway. We report the
      genetic engineering of herbicide resistance by stable integration of the petunia
      EPSPS gene into the tobacco chloroplast genome using the tobacco or universal
      vector. Southern blot analysis confirms stable integration of the EPSPS gene into
      all of the chloroplast genomes (5000-10,000 copies per cell) of transgenic
      plants. Seeds obtained after the first self-cross of transgenic plants germinated
      and grew normally in the presence of the selectable marker, whereas the control
      seedlings were bleached. While control plants were extremely sensitive to
      glyphosate, transgenic plants survived sprays of high concentrations of
      glyphosate. Chloroplast transformation provides containment of foreign genes
      because plastid transgenes are not transmitted by pollen. The escape of foreign
      genes via pollen is a serious environmental concern in nuclear transgenic plants
      because of the high rates of gene flow from crops to wild weedy relatives.

PMID- 9555725
TI  - Engineering passive immunity in transgenic mice secreting virus-neutralizing
      antibodies in milk.
AB  - Protection against enteric infections can be provided by the oral administration
      of pathogen-neutralizing antibodies. To provide passive immunity, 18 lines of
      transgenic mice secreting a recombinant monoclonal antibody (Mab) neutralizing
      transmissible gastroenteritis coronavirus (TGEV) into the milk were generated.
      The genes encoding a chimeric Mab with the variable modules of the murine TGEV
      specific Mab 6A.C3 and the constant modules of a human IgG, isotype Mab were
      expressed under the control of regulatory sequences derived from the whey acidic
      protein, which is an abundant milk protein. The Mab 6A.C3 binds to a highly
      conserved epitope present in coronaviruses of several species, which does not
      allow the selection of neutralization escape mutants. Antibody expression titers
      of 10(6) were obtained in the milk of transgenic mice that reduced TGEV
      infectivity 10(6)-fold. The antibody was synthesized at high levels throughout
      lactation. Integration of matrix attachment region sequences with the antibody
      genes led to a 20- to 10,000-fold increase in the antibody titer in 50% of the
      transgenic animals. Antibody expression levels were transgene copy number
      independent and related to the site of integration. The generation of transgenic
      animals producing virus neutralizing antibodies in milk could provide an approach
      to protection against neonatal infections of the enteric tract.

PMID- 9555726
TI  - Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA.
AB  - Peptide nucleic acid (PNA) is a DNA mimic with attractive properties for
      developing improved gene-targeted antisense agents. To test this potential of PNA
      in bacteria, PNAs were designed to target the start codon regions of the
      Escherichia coli beta-galactosidase and beta-lactamase genes. Dose-dependent and
      specific gene inhibition was observed in vitro using low nanomolar PNA
      concentrations and in vivo using low micromolar concentrations. Inhibition was
      more efficient for a permeable E. coli strain relative to wild-type K-12. The
      potency of the anti-beta-lactamase PNAs was abolished by a six base substitution,
      and inhibition could be re-established using a PNA with compensating base
      changes. Antisense inhibition of the beta-lactamase gene was sufficient to
      sensitize resistant cells to the antibiotic ampicillin. The results demonstrate
      gene- and sequence-specific antisense inhibition in E. coli and open
      possibilities for antisense antibacterial drugs and gene function analyses in
      bacteria.

PMID- 9555727
TI  - Molecular beacon sequence analysis for detecting drug resistance in Mycobacterium
      tuberculosis.
AB  - We developed a new approach to DNA sequence analysis that uses fluorogenic
      reporter molecules--molecular beacons--and demonstrated their ability to
      discriminate alleles in real-time PCR assays of genomic DNA. A set of overlapping
      molecular beacons was used to analyze an 81-bp region of the Mycobacterium
      tuberculosis rpoB gene for mutations that confer resistance to the antibiotic
      rifampin. In a blinded study of 52 rifampin-resistant and 23 rifampin-susceptible
      clinical isolates, this method correctly detected mutations in all of the
      resistant strains and in none of the susceptible strains. The assay was carried
      out entirely in sealed PCR tubes and was simple to perform and interpret. This
      approach can be used to analyze any DNA sequence of moderate length with single
      base pair accuracy.

PMID- 9555728
TI  - Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T
      lymphocytes in vitro using human dendritic cells transfected with RNA.
AB  - Dendritic cells (DC) generated from the peripheral blood mononuclear cells of
      healthy individuals or from cancer patients transfected with carcinoembryonic
      antigen (CEA) mRNA stimulate a potent CD8+ cytotoxic T lymphocyte (CTL) response
      in vitro. DCs are effectively sensitized with RNA in the absence of reagents
      commonly used to facilitate mammalian cell transfection. RNA encoding a chimeric
      CEA/LAMP-1 lysosomal targeting signal enhances the induction of CEA-specific CD4+
      T cells, providing a strategy to induce T-help that may be necessary to generate
      and/or maintain an optimal CD8+ CTL response in vivo. CEA RNA-transfected DCs
      also serve as effective targets in cytotoxicity assays, thus providing a general
      method for inducing, as well as measuring, CEA-specific CTL responses across a
      broad spectrum of HLA haplotypes.

PMID- 9555729
TI  - Genetic engineering of proteins with cell membrane permeability.
AB  - The discovery of methods for generating proteins with inherent cell membrane
      translocating activity will expand our ability to study and manipulate various
      intracellular processes in living systems. We report a method to engineer
      proteins with cell-membrane permeability. After a 12-amino acid residue membrane
      translocating sequence (MTS) was fused to the C-terminus of glutathione S
      transferase (GST), the resultant GST-MTS fusion proteins were efficiently
      imported into NIH 3T3 fibroblasts and other cells. To explore the applicability
      of this nondestructive import method to the study of intracellular processes, a
      41-kDa GST-Grb2SH2-MTS fusion protein containing the Grb2 SH2 domain was tested
      for its effect on the epidermal growth factor (EGF)-stimulated signaling pathway.
      This fusion protein entered cells, formed a complex with phosphorylated EGF
      receptor (EGFR), and inhibited EGF-induced EGFR-Grb2 association and mitogen
      activated protein kinase activation.

PMID- 9555731
TI  - Sequencing exons 5 to 8 of the p53 gene by MALDI-TOF mass spectrometry.
AB  - Matrix-assisted laser desorption ionization time of flight mass spectrometry was
      used to sequence exons 5 to 8 of the human p53 gene. A single tube procedure was
      established for target amplification and mass spectrometric (MS) sequencing. The
      MS sequencing scheme is designed for high throughput and parallel sample
      processing, and is amenable to full automation. Reliable sequencing data were
      obtained using fmol sample amounts. The high resolution and accuracy of MS
      sequencing was demonstrated by direct sequencing of a heterozygous template.

PMID- 9555730
TI  - Selection for a periplasmic factor improving phage display and functional
      periplasmic expression.
AB  - The efficiency of both phage display in Escherichia coli and periplasmic
      expression of recombinant proteins may be limited by the same periplasmic folding
      steps. To search for E. coli factors that improve the efficiency of both
      procedures, a library of E. coli proteins was coexpressed in a phagemid vector
      that contained a poorly folding single-chain Fv antibody (scFv) fragment fused to
      g3p. We enriched, by panning for antigen binding, those phagemids in which the
      amount of displayed scFv is highest. We thus identified the periplasmic protein
      Skp/OmpH/HlpA as improving phage display of a wide range of scFv fragments. This
      occurs as a result of an increase in the amount of hybrid protein displayed on
      the phage. Coexpression of skp also increases the functional yield of scFv
      fragments when expressed by secretion to the periplasm.

PMID- 9555732
TI  - Building a fast-track patent portfolio in the UK and Europe.

PMID- 9555733
TI  - Contract research organizations on the Web.

PMID- 9555734
TI  - Proteomics.

PMID- 9555735
TI  - Physician leadership on National Drug Policy finds addiction treatment works.

PMID- 9555736
TI  - Influenza vaccine virus strains chosen.

PMID- 9555737
TI  - Parity for mental health and substance abuse treatment.

PMID- 9555738
TI  - Fighting flora with flora: FDA approves an anti-Salmonella spray for chickens.

PMID- 9555739
TI  - From the Centers for Disease Control and Prevention. Progress toward elimination
      of measles from the Americas.

PMID- 9555740
TI  - From the Centers for Disease Control and Prevention. Update: Influenza activity-
      United States, 1997-98 season.

PMID- 9555742
TI  - From the Centers for Disease Control and Prevention. Imported dracunculiasis-
      United States, 1995 and 1997.

PMID- 9555741
TI  - From the Centers for Disease Control and Prevention. Update: HIV counseling and
      testing using rapid tests--United States, 1995.

PMID- 9555743
TI  - A piece of my mind. Remembering Jinx.

PMID- 9555744
TI  - Local anesthesia for infants undergoing circumcision.

PMID- 9555745
TI  - Local anesthesia for infants undergoing circumcision.

PMID- 9555746
TI  - Local anesthesia for infants undergoing circumcision.

PMID- 9555747
TI  - Local anesthesia for infants undergoing circumcision.

PMID- 9555748
TI  - Dietary fat and ischemic stroke.

PMID- 9555749
TI  - Dietary fat and ischemic stroke.

PMID- 9555750
TI  - Dietary fat and ischemic stroke.

PMID- 9555751
TI  - The 16th-century observations of Pieter Pauw: balancing humors and councils.

PMID- 9555752
TI  - The 16th-century observations of Pieter Pauw: balancing humors and councils.

PMID- 9555753
TI  - Injuries from dog bites.

PMID- 9555754
TI  - Injuries from dog bites.

PMID- 9555755
TI  - Injuries from dog bites.

PMID- 9555756
TI  - Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol
      poisoning. Acute Renal Failure Investigation Team.
AB  - CONTEXT: Contaminated pharmaceutical products can result in substantial morbidity
      and mortality and should be included in the differential diagnosis of deaths of
      unknown origin. OBJECTIVE: To investigate an outbreak of deaths among children
      from acute renal failure in Haiti to determine the etiology and institute control
      measures. DESIGN: Case-control study, cohort study, and laboratory toxicologic
      evaluation. SETTING: Pediatric population of Haiti. PARTICIPANTS: Cases were
      defined as Haitian residents younger than 18 years with idiopathic anuria or
      severe oliguria for 24 hours or longer. Febrile hospitalized children without
      renal failure were enrolled as control subjects. MAIN OUTCOME MEASURE: The odds
      of exposure to suspected etiologic agents among cases and controls. RESULTS: We
      identified 109 cases of acute renal failure among children. The clinical syndrome
      included renal failure, hepatitis, pancreatitis, central nervous system
      impairment, coma, and death. Of 87 patients with follow-up information who
      remained in Haiti for treatment, 85 (98%) died; 3 (27%) of 11 patients
      transported to the United States for intensive care unit management died before
      hospital discharge. A locally manufactured acetaminophen syrup was highly
      associated with disease (odds ratio, 52.7; 95% confidence interval, 15.2-197.2).
      Diethylene glycol (DEG) was found in patients' bottles in a median concentration
      of 14.4%. The median estimated toxic dose of DEG was 1.34 mL/kg (range, 0.22-4.42
      mL/kg). Glycerin, a raw material imported to Haiti and used in the acetaminophen
      formulation, was contaminated with 24% DEG. CONCLUSIONS: An epidemic of severe
      systemic toxicity and deaths from DEG-contaminated acetaminophen syrup occurred
      in Haiti. Good manufacturing practice regulations should be used by all
      pharmaceutical manufacturers to prevent such tragedies.

PMID- 9555757
TI  - Montelukast for chronic asthma in 6- to 14-year-old children: a randomized,
      double-blind trial. Pediatric Montelukast Study Group.
AB  - CONTEXT: Leukotrienes are important mediators of asthma by causing
      bronchoconstriction, mucous secretion, and increased vascular permeability.
      Studies using compounds that block leukotrienes have demonstrated improvement in
      asthma control in adults and adolescents, but children younger than 12 years, for
      whom asthma is the most common chronic disease, have not been studied. OBJECTIVE:
      To determine the clinical effect of montelukast, a leukotriene receptor
      antagonist, in 6- to 14-year-old children with asthma. DESIGN: Eight-week,
      multicenter, randomized, double-blind study. SETTING: Forty-seven outpatient
      centers at private practices and academic medical centers in the United States
      and Canada. PATIENTS: A total of 336 children with forced expiratory volume in 1
      second (FEV1) between 50% to 85% of the predicted value, at least 15%
      reversibility after inhaled beta-agonist administration, a minimal predefined
      level of daytime asthma symptoms, and daily beta-agonist use. Concomitant inhaled
      corticosteroids at a constant daily dose were used by 39% of patients receiving
      montelukast and 33% receiving placebo. INTERVENTION: After a 2-week placebo run
      in period, patients received either montelukast (5-mg chewable tablet) or
      matching-image placebo once daily at bed-time for 8 weeks. MAIN OUTCOME MEASURE:
      Morning FEV1 percent change from baseline. RESULTS: Mean morning FEV1 increased
      from 1.85 L to 2.01 L in the montelukast group and from 1.85 L to 1.93 L in the
      placebo group. This represents an 8.23% (95% confidence interval [CI], 6.33% to
      10.13%) increase from baseline in the montelukast group and a 3.58% (95% CI,
      1.29% to 5.87%) increase from baseline in the placebo group (P<.001 for
      montelukast vs placebo). CONCLUSION: Montelukast improves morning FEV1 in 6- to
      14-year-old children with chronic asthma.

PMID- 9555758
TI  - Importance of functional measures in predicting mortality among older
      hospitalized patients.
AB  - CONTEXT: Measures of physical and cognitive function are strong prognostic
      predictors of hospital outcomes for older persons, but current risk adjustment
      and burden of illness assessment indices do not include these measures.
      OBJECTIVE: To evaluate and validate the contribution of functional measures to
      the ability of 5 standard burden of illness indices (Charlson, Acute Physiology
      and Chronic Health Evaluation [APACHE] II, Disease Staging, All Patient Refined
      Diagnosis Related Groups, and a clinician's subjective rating) in predicting 90
      day and 2-year mortality among older hospitalized patients. DESIGN: Two
      prospective cohort studies. SETTING: General medicine service, university
      teaching hospital. PATIENTS: For the development cohort, 207 consecutive patients
      aged 70 years or older, and for the validation cohort, 318 comparable patients.
      MAIN OUTCOME MEASURE: Death within 90 days and 2 years from the index admission.
      RESULTS: In the development cohort, 29 patients (14%) and 81 patients (39%) died
      within 90 days and 2 years, respectively. A functional axis was developed using 3
      independent risk factors: impairment in instrumental activities of daily living,
      Mini-Mental State Examination score of less than 20, and shortened Geriatric
      Depression Scale score of 7 or higher, creating low-, intermediate-, and high
      risk groups with associated mortality rates of 20%, 32%, and 60%, respectively
      (P<.001); the C statistic for the final model was 0.69. The corresponding
      mortality rates in the validation cohort, in which 59 (19%) and 138 (43%) died
      within 90 days and 2 years, respectively, were 24%, 45%, and 60% (P<.001); the C
      statistic for the final model was 0.66. For each burden of illness index, the
      functional axis contributed significantly to the predictive ability of the model
      for both 90 days and 2 years. When the functional axis and each burden of illness
      measure were analyzed in cross-stratified format, mortality rates increased
      progressively from low-risk to high-risk functional groups within strata of
      burden of illness indices (double-gradient phenomenon). The contributions of
      functional and burden of illness measures were substantive and interrelated.
      CONCLUSIONS: Functional measures are strong predictors of 90-day and 2-year
      mortality after hospitalization. Furthermore, these measures contribute
      substantially to the prognostic ability of 5 burden of illness indices. Optimal
      risk adjustment for older hospitalized patients should incorporate functional
      status variables.

PMID- 9555759
TI  - Learning, satisfaction, and mistreatment during medical internship: a national
      survey of working conditions.
AB  - CONTEXT: Concerns about the working and learning environment of residency
      training continue to surface. Previous surveys of residents have focused on work
      hours and income, but have shed little light on how residents view their training
      experience. OBJECTIVE: To provide a description of the internship year as seen by
      a large cross section of second-year residents. DESIGN: Mail survey conducted in
      1991. SETTING: Residency programs in the United States. PARTICIPANTS: Random 10%
      sample (N=1773) of all second-year residents listed in the American Medical
      Association's medical research and information database. MAIN OUTCOME MEASURES:
      What and who contributes most to residents' learning during internships, degree
      of satisfaction with the internship experience, on-call and sleep schedules,
      incidents of perceived mistreatment or abuse, observations of unethical behavior,
      and experiences of harassment or discrimination. RESULTS: A total of 1277 surveys
      (72%) of 1773 mailed were returned. Overall, respondents reported a moderate
      level of satisfaction with their first year of residency. On a scale of 0 to 3,
      residents rated other residents as contributing most (score of 2.3) to their
      learning, with special patients ranked second (2.1). During a typical work week,
      residents reported that they spent an average of 56.9 hours on call in the
      hospital. A total of 1185 (93%) residents reported experiencing at least 1
      incident of perceived mistreatment, with 53% reporting being belittled or
      humiliated by more senior residents. Among women residents, 63% reported having
      experienced at least 1 episode of sexual harassment or discrimination. A total of
      45% of residents reported having observed another individual falsifying medical
      records, and 70% saw a colleague working in an impaired condition, most often
      lack of sleep. Regression analyses suggest that satisfaction with the residency
      experience was associated with the presence of factors that enhanced learning,
      and fewer experiences of perceived mistreatment. CONCLUSIONS: Residents report
      significant problems during their internship experience. Satisfaction with
      internship is enhanced by positive learning experiences and lack of mistreatment.

PMID- 9555760
TI  - Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of
      prospective studies.
AB  - OBJECTIVE: To estimate the incidence of serious and fatal adverse drug reactions
      (ADR) in hospital patients. DATA SOURCES: Four electronic databases were searched
      from 1966 to 1996. STUDY SELECTION: Of 153, we selected 39 prospective studies
      from US hospitals. DATA EXTRACTION: Data extracted independently by 2
      investigators were analyzed by a random-effects model. To obtain the overall
      incidence of ADRs in hospitalized patients, we combined the incidence of ADRs
      occurring while in the hospital plus the incidence of ADRs causing admission to
      hospital. We excluded errors in drug administration, noncompliance, overdose,
      drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as
      those that required hospitalization, were permanently disabling, or resulted in
      death. DATA SYNTHESIS: The overall incidence of serious ADRs was 6.7% (95%
      confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%
      0.41%) of hospitalized patients. We estimated that in 1994 overall 2216000
      (1721000-2711000) hospitalized patients had serious ADRs and 106000 (76000
      137000) had fatal ADRs, making these reactions between the fourth and sixth
      leading cause of death. CONCLUSIONS: The incidence of serious and fatal ADRs in
      US hospitals was found to be extremely high. While our results must be viewed
      with circumspection because of heterogeneity among studies and small biases in
      the samples, these data nevertheless suggest that ADRs represent an important
      clinical issue.

PMID- 9555761
TI  - Prevention of invasive group A streptococcal disease among household contacts of
      case-patients: is prophylaxis warranted? The Working Group on Prevention of
      Invasive Group A Streptococcal Infections.
AB  - OBJECTIVES: The Centers for Disease Control and Prevention (CDC) convened a
      Working Group in October 1995 to summarize the data regarding the risk of
      invasive group A streptococcal (GAS) disease among household contacts of an index
      patient and the potential efficacy of chemoprophylaxis. This statement on
      chemoprophylaxis for prevention of subsequent cases among household contacts is
      intended for use by public health professionals and clinicians. PARTICIPANTS: The
      CDC invited representatives of the American Academy of Pediatrics, the Council of
      State and Territorial Epidemiologists, the Hospital Infection Control Practice
      Advisory Committee, the Infectious Diseases Society of America, and experts from
      academia to participate. EVIDENCE: Data on the transmission of GAS and risk
      factors for severe infection were considered. Population-based surveillance data
      were used to estimate the risk of invasive GAS disease among household contacts
      of a case patient. The potential efficacy of chemoprophylaxis was considered
      using estimates of the efficacy of various regimens in eradicating pharyngeal
      carriage. CONSENSUS PROCESS: This document summarizes the data considered by the
      Working Group to develop its position. The consensus achieved by group discussion
      at the meeting was incorporated in a draft document, which was reviewed by all
      members and revised to include suggested changes. CONCLUSIONS: The Working Group
      concluded that no definite recommendations can be made at this time regarding
      chemoprophylaxis for household contacts of persons with invasive GAS infection.
      More data are needed to assess the risk of subsequent cases and to determine an
      optimal regimen for chemoprophylaxis. Until such data are available, physicians
      and health departments should base decisions regarding chemoprophylaxis on their
      assessment of the risk associated with each individual case.

PMID- 9555762
TI  - Hunger in an adult patient population.
AB  - CONTEXT: Although clinical observations suggest that some patients experience
      hunger and food insecurity, there are limited data on the prevalence of hunger in
      adult patients. OBJECTIVE: To determine the prevalence of hunger and food
      insecurity in adult patients at an urban county hospital. DESIGN: Cross-sectional
      survey conducted in 1997. PATIENTS: The primary survey included all patients aged
      18 years or older who were admitted to the medicine, surgery, and neurology
      services during a 2-week period, and all patients who attended the hospital's
      general medicine clinic during 1 week. A second survey included primary care
      patients who received insulin from the hospital pharmacy during a 1-month period.
      MAIN OUTCOME MEASURES: Rates of hunger and food insecurity. RESULTS: Of 709
      eligible patients, 567 (participation rate, 80%) were interviewed in either the
      clinic (n=281) or hospital (n=286). An additional 170 patients who received
      insulin were interviewed by telephone (response rate, 75%). Of the primary
      sample, 68 (12%) respondents reported not having enough food, 75 (13%) reported
      not eating for an entire day, and 77 (14%) reported going hungry but not eating
      because they could not afford food. A total of 222 (40%) had received food stamps
      in the previous year and of those, 113 (50%) had their food stamps reduced or
      eliminated. Recipients whose food stamps had been eliminated or reduced were more
      likely to report not having enough food (18% vs 13%, P=.006), not eating for a
      whole day (20% vs 16%, P=.01), going hungry but not eating (20% vs 16%, P=.08),
      and cutting down on the size of meals or skipping meals (33% vs 27%, P=.01). In
      multivariate analysis, independent predictors of hunger included an annual income
      of less than $10000 (odds ratio [OR], 7.55; 95% CI, 3.01-18.92), drug use (OR,
      3.56; 95% CI, 1.46-8.66), and a reduction in food stamp benefits (OR, 1.73; 95%
      CI, 1.01-2.96). Predictors of food insecurity included an annual income of less
      than $10000 (OR, 4.12; 95% confidence interval [CI], 1.98-8.58), drug use (OR,
      2.11; 95% CI, 1.66-5.08), and a reduction in food stamps (OR, 2.02; 95% CI, 1.23
      3.32). In addition, 103 (61%) patients in the sample of diabetics reported
      hypoglycemic reactions; 32 (31%) of these were attributed to inability to afford
      food. CONCLUSION: Hunger and food insecurity are common among patients seeking
      care at an urban county hospital.

PMID- 9555763
TI  - The Haitian diethylene glycol poisoning tragedy: a dark wood revisited.

PMID- 9555765
TI  - A privacy primer for the Web: spam, bread crumbs, and cookies.

PMID- 9555764
TI  - Drugs and adverse drug reactions: how worried should we be?

PMID- 9555766
TI  - Management of adults recovering from alcohol or other drug problems: relapse
      prevention in primary care.
AB  - Patients recovering from substance use disorders are commonly seen in the primary
      care setting, and relapse is a serious long-term problem for these patients.
      Extrapolating from therapeutic strategies effective in specialty addiction
      treatment settings, this article outlines a practical approach to relapse
      prevention in the primary care setting. Working within a supportive patient
      physician relationship, the primary care physician can help recovering patients
      decrease their susceptibility to relapse, recognize and manage high-risk
      situations, and use available self-help, pharmacological, and specialty
      resources. Drawing on the therapeutic relationship and skills they already
      possess, primary care physicians can have an important, productive, and
      satisfying role in the long-term management of patients in recovery from alcohol
      or other drug problems.

PMID- 9555767
TI  - Comparison of the various electrocardiographic scoring codes for estimating
      anatomically documented sizes of single and multiple infarcts of the left
      ventricle.
AB  - It is clinically important to estimate the size of a myocardial infarction (MI)
      to predict patient prognosis, to determine the ability of a therapy to limit its
      size, and to evaluate its effect on left ventricular function. Various
      electrocardiographic methods have been used for these purposes but their
      accuracies have not been compared with each other using an identical reference
      population of anatomically measured infarcts. The capability of 4
      electrocardiographic scoring methods (the Selvester score, the Minnesota code,
      the Novacode, and the Cardiac Infarction Injury Score) to estimate MI size was
      compared using anatomic MI size in a group of 100 deceased patients. All patients
      had a standard 12-lead electrocardiogram of sufficient quality to perform manual
      waveform measurements and without confounding factors such as ventricular
      hypertrophy, fascicular block, or bundle branch block. The location and size of
      the left ventricular infarction was measured postmortem using the anatomic method
      of Ideker et al. All methods' size estimates correlated best with anatomic MI
      size in the anterior location (r = 0.65 to 0.89). The Selvester score was
      superior in estimating the sizes of inferior (r = 0.70) and posterolateral (r =
      0.74) infarcts. For multiple infarcts all methods performed poorly (r = 0.18 to
      0.44).

PMID- 9555768
TI  - Relation between exercise-induced myocardial ischemia as assessed by nitrogen-13
      ammonia positron emission tomography and QT interval behavior in patients with
      right bundle branch block.
AB  - Exercise-induced myocardial ischemia is difficult to detect with ST-T changes in
      patients with right bundle branch block (RBBB). We sought to predict exercise
      induced myocardial ischemia with QT interval behavior during exercise in patients
      with RBBB. Twenty-two patients with angiographically proven coronary artery
      disease and RBBB and 9 healthy volunteers underwent nitrogen-13 ammonia positron
      emission tomography with bicycle ergometer exercise at a fixed workload of 25 W.
      Regional myocardial blood flow (RMBF) and electrocardiographic changes were
      measured both at rest and after 5 minutes of exercise. The QT interval was
      measured from the onset of the QRS complex to the offset of the T wave in lead
      V5. The deltaQT and deltaRMBF, which indicated values after 5 minutes of exercise
      minus values at rest, were negatively correlated (r = -0.74, p <0.001). Exercise
      induced shortening of the QT interval (422 +/- 27 to 381 +/- 38 ms, p = 0.0020)
      was observed in 15 patients (group 1) and no change or prolongation (411 +/- 45
      to 420 +/- 37 ms, p = NS) was observed in 7 patients (group 2). Multivessel
      disease was significantly more frequent but collateral circulation was
      significantly less in group 2 than in group 1 (p <0.01, p <0.05, respectively).
      Cardiac output at rest was significantly lower in groups 1 and 2 than in healthy
      volunteers (4.52 +/- 0.83 and 4.51 +/- 0.84 vs 6.20 +/- 0.83 L/min; p = 0.0014, p
      = 0.0003). Although RMBF at rest did not differ significantly among groups 1 and
      2 and healthy volunteers (0.63 +/- 0.20 vs 0.69 +/- 0.13 and vs 0.77 +/- 0.14
      ml/min/g), RMBF after 5 minutes of exercise was significantly lower in group 2
      than in group 1 and healthy volunteers (0.78 +/- 0.11 vs 0.96 +/- 0.20 and vs
      1.20 +/- 0.18 ml/min/g; p = 0.0289, p <0.0001). The number of regions of critical
      coronary artery disease was significantly greater in group 2 than in group 1 (4.0
      +/- 1.2 vs 2.1 +/- 1.3, p = 0.0039). Our results suggest that the absence of QT
      interval shortening during exercise may indicate severe myocardial ischemia
      induced by exercise in patients with RBBB and coronary artery disease.

PMID- 9555769
TI  - Predischarge two-dimensional echocardiographic evaluation of left ventricular
      thrombosis after acute myocardial infarction in the GISSI-3 study.
AB  - Left ventricular (LV) thrombosis can be found in patients with acute myocardial
      infarction (AMI). No wide multicenter trial on AMI has provided information about
      LV thrombosis until now. The protocol of the GISSI-3 study included the search
      for the presence of LV thrombosis in patients from 200 coronary care units that
      did not specifically focus on LV thrombosis. We examined the GISSI-3 database
      results related to 8,326 patients at low to medium risk for LV thrombi in which a
      predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found
      in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in
      135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence
      of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of
      1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and
      in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p
      <0.0001). Multivariate analysis showed that only the Killip class > I and early
      intravenous beta-blocker administration were independently associated with higher
      LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio
      1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence
      interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta
      blocker therapy given or not given after early intravenous beta-blocker
      administration does not influence the occurrence of LV thrombosis. The rate of LV
      thrombosis was similar in patients treated or not treated with nitrates and
      lisinopril both in the total population and in patients with anterior and
      nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk
      for LV thrombi, the highest rate of occurrence of LV thrombosis was found among
      patients with anterior AMI and an ejection fraction < 40%. Killip class > I and
      the early intravenous beta-blocker administration were the only variables
      independently associated with a higher predischarge incidence of LV thrombosis
      after anterior AMI.

PMID- 9555770
TI  - Asynergy of the noninfarcted left ventricular inferior wall in anterior wall
      acute myocardial infarction secondary to isolated occlusion of the left anterior
      descending artery.
AB  - There are patients in whom left ventricular (LV) wall motion decreases in the
      noninfarcted region and LV systolic function declines globally despite the
      presence of a localized myocardial infarct attributable to narrowing or occlusion
      of a single coronary artery. This study examines angiographic characteristics of
      patients with chronic hypokinesia of noninfarcted myocardium after anterior wall
      acute myocardial infarction (AMI) due to narrowing of a single coronary artery,
      namely, the left anterior descending (LAD) artery. The LV ejection fraction,
      abnormalities in the motion of the noninfarcted LV inferior wall (SD/chord value
      by Sheehan's technique), the angiographic characteristics of the infarct-related
      coronary artery, the effect of acute reperfusion therapy, and presence of
      coronary risk factors were examined in 85 consecutive patients. The SD/chord
      value in the noninfarcted region showed a positive correlation with the LV
      ejection fraction (r = 0.505, p <0.0001). By multivariate analysis, hypertension
      (odds ratio = 0.53, 95% confidence interval [CI] 0.36 to 0.80), an infarct
      related narrowing proximal to the origin of the first diagonal branch (odds ratio
      = 0.56, 95% CI 0.38 to 0.84), and patency of the infarct-related lesion during
      AMI (odds ratio = 1.56, 95% CI 1.03 to 2.30) were independent predictors of wall
      motion in the noninfarct region. In some patients with single-vessel anterior
      wall AMI, the motion of the noninfarcted inferior LV wall decreases during the
      chronic stage and cardiac function declines severely. In most of these patients,
      the infarct-related narrowing or occlusion is proximal to the origin of the first
      diagonal branch of the LAD artery.

PMID- 9555771
TI  - Effects of cardiac rehabilitation and beta-blocker therapy on heart rate
      variability after first acute myocardial infarction.
AB  - After acute myocardial infarction (AMI), rehabilitation with physical training
      increases parasympathetic tone. It is unknown whether such a favorable effect of
      exercise on the sympathovagal balance interacts with effects of other widespread
      therapies, such as beta blockers. In 53 patients after a first, uncomplicated
      AMI, we studied the combined short- and long-term influence on heart rate
      variability (HRV) of rehabilitation and beta blockade. Patients were divided into
      3 groups: group 1 (n = 19) underwent rehabilitation with physical training; group
      2 (n = 20) was taking beta blockers and underwent rehabilitation; group 3 (n =
      14) was taking beta blockers and did not enter the rehabilitation program for
      logistic reasons. Patients were similar as to age, site of infarction, ejection
      fraction, left ventricular diameter, and baseline stress test duration. Measures
      of HRV (obtained from a 15-minute resting electrocardiogram) were the standard
      deviation of the mean RR interval (RRSD), the mean squared successive differences
      (MSSD), the percent of RR intervals differing >50 ms from the preceding one
      (pNN50), the low-(LF) and high-(HF) frequency components of the autoregressive
      power spectrum of the RR intervals and their ratio (LF/HF). Four weeks after AMI,
      there was less sympathetic predominance in groups 2 and 3 (i.e., patients taking
      beta blockers [p <0.05]). Rehabilitation modified HRV in groups 1 and 2 (p
      <0.05), with signs of increased parasympathetic tone (group 1: MSSD +25%, pNN50
      +69%, LF/HF -40%; group 2: MSSD +41%, pNN50 +48%, LF/HF -39%). These changes
      persisted in the long term. In group 3, HRV was unchanged over time. Hence, after
      AMI, the effects of rehabilitation and beta blockers on HRV are not redundant:
      their association induces a more favorable sympathovagal balance, accelerating
      the recovery of a normal autonomic profile.

PMID- 9555773
TI  - Coronary angioplasty outcomes in the Healthcare Cost and Utilization Project,
      1993-1994.
AB  - It is estimated that >400,000 percutaneous transluminal coronary angioplasty
      (PTCA) procedures are performed in the Unites States annually. This study reports
      patient characteristics and outcomes for 163,527 PTCAs performed in 214 hospitals
      in 17 states from 1993 to 1994. These hospitals were a 20% random sample of
      hospitals in the Healthcare Cost and Utilization Project, which was designed to
      reflect hospitalization in the United States, generally. Cases with International
      Classification of Diseases, 9th Revision, Clinical Modification procedure codes
      36.01, 36.02, and 36.05 were defined as PTCA and were categorized as to whether
      acute myocardial infarction (AMI) was the principal discharge diagnosis. The
      average age of 44,270 AMI discharges (27%) was 62 +/- 12 years and that of
      119,257 no-AMI cases (73%) was 64 +/- 11 years; 1/3 of both groups were women,
      88% were white, and almost 90% had Medicare or private insurance as the primary
      payer. The states contributing the most cases were Florida (26%), California
      (12%), and Wisconsin (10%). Hospital mortality was 1.7% overall and was 3.8% for
      AMI and 0.8% for no-AMI cases. Bypass surgery performed during the same admission
      was 3.4% overall and was 4.5% and 3.0% for AMI and no-AMI cases, respectively.
      Multivariate analysis showed that advanced age, diabetes, female gender, and
      Medicaid payer status were associated with increased risk of mortality. National
      estimates from this 20% sample indicate that >850,000 PTCAs were performed in the
      2 years, with 452,319 cases estimated for 1994. In 1994 there were an estimated
      2,789 deaths and 9,903 bypass surgeries in the no-AMI subset of 327,856
      procedures. For the AMI group of 124,463 procedures, there were 4,486 deaths and
      5,799 bypass surgeries in 1994. This study of PTCA outcomes contains the largest
      number of cases as well as the most representative sample reported to date.

PMID- 9555772
TI  - Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant
      activation during alteplase double-bolus regimen in acute myocardial infarction.
AB  - Recent clinical studies comparing accelerated versus bolus administration of
      alteplase tissue plasminogen activator (t-PA) suggest similar thrombolytic
      efficacy, but reveal higher bleeding complications among older patients during
      the double-bolus regimen. The objective of the present study was to characterize
      the hemostatic profile of t-PA administered as double-bolus doses of 50 mg, at
      intervals of 30 minutes. Among 50 patients with acute myocardial infarction
      treated by double-bolus t-PA thrombolysis, coagulation and fibrinolysis
      parameters, as well as t-PA levels, were monitored. Monitored t-PA levels peaked
      at 5 and 35 minutes and were detectable within the therapeutic range even after
      90 minutes. Marked systemic fibrinolytic activation was indicated by 75%
      depletion of both plasminogen and fibrinogen, as well as by 19-fold and 300-fold
      increases of fibrin degradation and fibrinogen degradation products. Plasminogen
      activator inhibitor activity was completely suppressed. Pronounced procoagulant
      activation was reflected by a 3.4-fold increase of both factor XIIa and
      prothrombin fragment 1+2, and by a threefold increase of thrombin-antithrombin
      complex. Independent of t-PA weight dosage, fibrinolytic activation was more
      pronounced among older patients (> or = 63 years). We conclude that t-PA after
      bolus administration has a long half-life. Double-bolus regimen leads to a long
      lasting systemic fibrinolytic state, which is even more remarkable among older
      patients--a fact that may explain the higher bleeding complications reported for
      this age group.

PMID- 9555774
TI  - Continuous monitoring of global left ventricular ejection fraction during
      percutaneous transluminal coronary angioplasty.
AB  - Continuous monitoring of left ventricular (LV) function during percutaneous
      transluminal coronary angioplasty (PTCA) was performed in 40 patients (53 +/- 2
      years) with a miniature, nuclear detector system after labeling the patients' red
      blood cells with technetium-99m. Balloon dilation (113 seconds, range 60 to 240)
      induced on average a 0.12 ejection fraction (EF) unit (19%) decrease in the LVEF,
      which was explained by a 34% increase in end-systolic counts. Balloon dilation of
      the left anterior descending artery (n = 23) produced a decrease in the LVEF of
      0.17 +/- 0.13 EF units compared with the decrease of 0.06 +/- 0.07 EF units in
      patients undergoing dilation of the left circumflex artery (n = 9) and 0.05 +/-
      0.04 EF units in patients treated for a stenosis of the right coronary artery (n
      = 8), (p = 0.02). Balloon deflation was associated with an immediate return to
      pre-PTCA levels. In 10 patients with 2 identical balloon occlusions, the second
      occlusion led to a significantly less decrease in the LVEF (0.41 +/- 0.14 vs 0.44
      +/- 0.15) and electrocardiographic ST-segment deviation (88 +/- 54 microV vs 65
      +/- 42 microV) than the first. We conclude that PTCA is associated with an abrupt
      transient decrease in the LVEF. The effect of balloon occlusion of the left
      anterior descending artery is more pronounced than balloon occlusion of the left
      circumflex and the right coronary arteries. Neither single nor multiple balloon
      occlusions were associated with post-PTCA global LV dysfunction, whereas the
      lesser degree of LV dysfunction and electrocardiographic signs of myocardial
      ischemia during the second of 2 identical balloon occlusions suggests that
      preconditioning can be induced during PTCA.

PMID- 9555775
TI  - One-year follow-up of the Stent Restenosis (STRESS I) Study.
AB  - We present the completed 1-year follow-up results of the original Stent
      Restenosis Study (STRESS I), in which 407 patients with symptomatic ischemic
      heart disease and new lesions of the native coronary circulation were randomly
      assigned to treatment with either the Palmaz-Schatz coronary stent or
      conventional percutaneous transluminal coronary angioplasty (PTCA). The present
      study compares the safety of elective stenting to balloon angioplasty (PTCA) in
      terms of freedom from clinical events up to 1 year after treatment. Patients were
      enrolled and treated from January 1991 through February 1993, and follow-up data
      were collected and verified until July 1995. Ninety-seven percent of all patients
      had complete follow-up (deceased or alive with known clinical status) beyond 8
      months, and 94% beyond 11 months. Anginal status between 9 to 15 months
      postprocedure was available for 78% of patients. At 1 year, 154 patients (75%)
      assigned to stent implantation and 141 (70%) to PTCA were free of all clinical
      events (death, myocardial infarction, or any revascularization procedure), and
      162 stent patients (79%) and 149 PTCA patients (74%) were free from death,
      myocardial infarction, or target lesion revascularization. Symptom-driven target
      lesion revascularization occurred in 12% of the stent group versus 17% of the
      PTCA group. None of these differences in clinical events was statistically
      significant. Only 2 patients in the stent group and 7 in the PTCA group had a
      first event after 239 days, and freedom from angina at 1 year was reported in
      equal frequency in both groups (84%). There appear to be no late adverse effects
      of stent implantation. However, these results are limited by low statistical
      power, narrow patient selection, and the anticoagulation regimen used in the
      early experience with this device.

PMID- 9555776
TI  - High anti-cytomegalovirus (CMV) IgG antibody titer is associated with coronary
      artery disease and may predict post-coronary balloon angioplasty restenosis.
AB  - Recent studies have demonstrated that cytomegalovirus (CMV) DNA was found in
      atherosclerotic coronary arteries in restenotic lesions, and prior infection with
      CMV could be a strong independent risk factor for restenosis after coronary
      atherectomy. We studied the correlation between anti-CMV antibody titer and
      coronary artery disease. Sixty-five patients (50 men and 15 women) with coronary
      artery disease were enrolled prospectively. All had symptomatic coronary artery
      disease with an angiographic documentation of a de novo single coronary lesion.
      All underwent balloon coronary angioplasty and were followed for 12 months with a
      thallium perfusion scan 3 months after angioplasty. Patients who had recurrent
      chest pain and/or a positive thallium scan had another coronary angiography.
      Blood samples were taken before angiography and 1 and 3 months later. Patients
      with high anti-CMV titer > or = 1:800 had a higher prevalence of coronary artery
      disease (p <0.001) than seropositive patients with a lower antibody titer (< or =
      1:400); patients with high antibody titer (> or = 1:800) had a higher restenosis
      rate than seropositive patients with a low antibody titer (< or = 1:400) (p
      <0.05). High antibody titers against CMV (IgG) may be a strong marker for
      coronary artery disease, and might predict post-coronary angioplasty restenosis.
      These findings support the infectious theory of atherosclerosis (especially with
      prior CMV infection), and also suggest that a chronic immunologic response has a
      role in atherosclerosis and restenosis.

PMID- 9555777
TI  - Mortality in the Survival With ORal D-sotalol (SWORD) trial: why did patients
      die?
AB  - The Survival With ORal D-sotalol (SWORD) trial tested the hypothesis that the
      prophylactic administration of oral d-sotalol would reduce total mortality in
      patients surviving myocardial infarction (MI) with a left ventricular ejection
      fraction (LVEF) of < or = 40%. Two index MI groups were included: recent (6 to 42
      days) and remote (> 42 days) with clinical heart failure (n = 915 and 2,206,
      respectively). The trial was discontinued when the statistical boundary for harm
      was crossed (RR = 1.65; p = 0.006). All baseline variables known to be associated
      with mortality risk (e.g., LVEF, heart failure class, age) as well as variables
      related to torsades de pointes (e.g., time from beginning of therapy, QTc,
      gender, potassium, renal function, dose of d-sotalol) were assessed for
      interaction of each variable with treatment assignment, computing RR and 95%
      confidence interval (CI) from Cox regression models. The d-sotalol-associated
      mortality was greatest in the group with remote MI and LVEFs of 31% to 40% (RR =
      7.9; 95% CI 2.4 to 26.2). Most variables known to be associated with torsades de
      pointes were not differentially predictive of d-sotalol-associated risk, except
      female gender (RR = 4.7; 95% CI 1.4 to 16.5). These findings suggest that (1)
      most of the d-sotalol-associated risk was in patients remote from MI with a LVEF
      of 31% to 40%; comparable placebo patients had a very low mortality (0.5%); and
      (2) very little objective data supports torsades de pointes or any specific
      proarrhythmic mechanism as an explanation for d-sotalol-associated mortality
      risk.

PMID- 9555778
TI  - Design of a clinical trial for the assessment of cardioversion using
      transesophageal echocardiography (The ACUTE Multicenter Study). Steering and
      Publications Committees of the ACUTE Study.
AB  - Patients with atrial fibrillation (AF) undergoing cardioversion are at an
      increased risk of cardioembolic stroke and require anticoagulation. The
      Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE)
      Multicenter Study is a randomized clinical trial of patients undergoing
      electrical cardioversion of AF of >2 days' duration comparing a transesophageal
      guided strategy (TEE) with brief anticoagulation to the conventional
      anticoagulation strategy. Patients randomly assigned to the TEE-guided strategy
      receive therapeutic anticoagulation before TEE and cardioversion, followed by 4
      weeks of anticoagulation. Patients with thrombus imaged by TEE have postponement
      of cardioversion, continue anticoagulation for 3 weeks, and undergo a repeat TEE.
      Conventional strategy patients receive 3 weeks of anticoagulation before
      cardioversion, followed by 4 weeks of anticoagulation after cardioversion. The
      primary end point events are ischemic stroke, transient ischemic attack, and
      systemic embolization for an 8-week period from enrollment. Secondary end points
      are major and minor bleeding, all-cause mortality, successful return to and
      maintenance of sinus rhythm, and cost effectiveness. Analysis is based on the
      intention-to-treat principle. The anticipated rates of embolism of 2.9% for
      conventional strategy and 1.2% for the TEE-guided strategy are based on published
      research and the completed pilot study. The ACUTE Multicenter Study will
      randomize therapy and follow an estimated 3,000 patients from 65 study sites to
      determine the relative efficacy of the TEE-guided and conventional approaches to
      electrical cardioversion for patients in AF. The results of this investigation
      will have important clinical implications for the management of patients with AF
      undergoing electrical cardioversion.

PMID- 9555779
TI  - Comparison of clinical and morphologic cardiac findings in patients having
      cardiac transplantation for ischemic cardiomyopathy, idiopathic dilated
      cardiomyopathy, and dilated hypertrophic cardiomyopathy.
AB  - This article compares intergroup and intragroup clinical and morphologic findings
      in patients with ischemic cardiomyopathy (IC), idiopathic dilated cardiomyopathy
      (IDC), and dilated hypertrophic cardiomyopathy (HC) undergoing cardiac
      transplantation (CT). Few previous publications have described findings in native
      hearts explanted at the time of CT. The explanted heart in 92 patients having CT
      was examined in uniform manner with particular attention to the sizes of the
      ventricular cavities and the presence of and extent of ventricular scarring. Of
      the 92 hearts examined, 47 had IC, 35 had IDC, and 10 had dilated HC. Although
      considerable degrees of intragroup variation occurred, the mean degree of left
      ventricular dilatation was similar among the patients with IC, IDC, and dilated
      HC. All patients with IC had left ventricular free wall scarring more extensive
      than that involving the ventricular septum, but the intragroup variation in the
      amounts of scarring was considerable. Nine of the 10 patients with dilated HC
      also had ventricular wall scarring, but it was more extensive in the ventricular
      septum than in the left ventricular free wall and involvement of the right
      ventricular wall also was present. Eight (23%) of the 35 IDC patients also had
      grossly visible ventricular scars but they were small and only 1 of the 8 had
      coronary narrowing and that was not in the distribution of the scarring.
      Narrowing of 1 or more epicardial coronary arteries >75% in cross-sectional area
      by plaque was present in all 47 IC patients, in 8 of the 35 IDC patients (7 had
      no ventricular scars), and in none of the 10 dilated HC patients. Coronary
      angiography was the major clinical tool allowing separation of the IC, IDC, and
      HC patients. Coronary angiography did not detect narrowing in any of the 8
      patients with IDC who were found to have coronary narrowing on anatomic study.
      Thus, among patients with IC, IDC, and dilated HC having CT, distinctive anatomic
      features allow separation of patients with IC, IDC, and dilated HC, but within
      each group considerable variation in left ventricular cavity size and extent of
      ventricular scarring occurs.

PMID- 9555780
TI  - Low-dose dobutamine stress echocardiography in children and young adults.
AB  - Dobutamine stress echocardiography has become widely accepted in the evaluation
      of adult patients with coronary heart disease. We wanted to assess the
      feasibility and the physiologic responses of stress echocardiography at low doses
      of dobutamine in a population of normal children and adults. Once achieved, we
      submitted a group of post-anthracycline patients to the test to assess the
      sensitivity of low-dose dobutamine stress echocardiography in the detection of
      cardiac dysfunction. Thirty-two healthy children and young adults (19 male and 13
      female subjects, median age 15 years [range 6 to 26]) were studied. After the
      initial study of normal subjects, we submitted a cohort of 39 patients (18 female
      and 21 male, aged 6 to 25 years), who completed anthracycline chemotherapy, to
      the same protocol. Dobutamine was infused at rates of 0.5 to 2.5 and 5
      microg/kg/min and echocardiographic measurements were obtained at rest and at the
      end of each stage. The test could be completed in 100% of the subjects without
      major complications. Statistically significant differences between resting
      echocardiographic values of systolic and diastolic function and values at 2.5 and
      5 microg/kg/min of dobutamine were found. Moreover, dobutamine revealed or
      enhanced differences between normal subjects and the post-anthracycline patients.
      Thus, low-dose dobutamine stress echocardiography is feasible and safe in older
      children. The test is very sensitive for the detection of subclinical cardiac
      dysfunction in post-anthracycline patients and could possibly assess functional
      myocardial reserve.

PMID- 9555781
TI  - Jesse Efrem Edwards, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 9555782
TI  - Consensus for the use of fibrates in the treatment of dyslipoproteinemia and
      coronary heart disease. Fibrate Consensus Group.
AB  - The hypolipidemic action of fibrates has recently been shown to involve the
      activation of peroxisome proliferator activated receptors establishing a
      molecular mechanism for this class of drugs. Increasing clinical trial evidence
      supports the efficacy of fibrates in the treatment of dyslipoproteinemias,
      particularly in patients with hypertriglyceridemia and low high-density
      lipoproteins.

PMID- 9555783
TI  - Usefulness of ST-segment elevation in lead III exceeding that of lead II for
      identifying the location of the totally occluded coronary artery in inferior wall
      myocardial infarction.
AB  - The presence of ST-segment elevation in lead III exceeding that of lead II,
      particularly if combined with ST elevation in lead V1, proved to be a powerful
      marker for occlusion of the proximal or midportion of the right coronary artery.
      These findings helped to determine the extent of myocardium at risk in inferior
      wall myocardial infarction and may further guide the decision to administer
      thrombolytics.

PMID- 9555784
TI  - Left ventricular function and coagulation activity in healed myocardial
      infarction.
AB  - We investigated the plasma levels of molecular markers for the thrombotic and
      fibrinolytic status in patients with healed myocardial infarction to determine
      the relation between left ventricular (LV) function and coagulation activity. Our
      findings demonstrated that the coagulation activity was increased in patients
      with healed myocardial infarction along with LV dysfunction, suggesting that
      anticoagulant therapy is considered in patients with severe LV dysfunction to
      prevent systemic thromboembolism.

PMID- 9555785
TI  - Effect of atenolol or metoprolol on waking hour dynamics of the QT interval in
      myocardial infarction.
AB  - In subjects with a recent acute myocardial infarction, the hour immediately
      following awakening is associated with an abrupt exaggeration of heart rate
      dependent changes and variability of the QT interval. Beta blockers were observed
      to blunt these waking hour changes.

PMID- 9555786
TI  - Early experience with the NIR intracoronary stent.
AB  - Immediate and midterm results of 61 NIR stent placement attempts in 55 native
      coronary vessels in 52 patients demonstrate a high clinical success rate of 98%,
      no early stent thrombosis, and a 5-month angiographic restenosis rate of 23%. The
      frequency of in-stent restenosis was significantly heightened in small vessel
      sizes and in diabetic patients.

PMID- 9555787
TI  - Lipid lowering in a multidisciplinary clinic compared with primary physician
      management.
AB  - A multidisciplinary lipid reduction clinic achieved greater reduction of serum
      cholesterol when compared with primary physicians among patients with coronary
      heart disease. The lipid clinic was more likely than the primary physicians to
      prescribe lipid-lowering medication, to prescribe multiple medications, and to
      use drug doses in excess of the "starting dose."

PMID- 9555788
TI  - On the necessity of the invasive predischarge test after implantation of a
      cardioverter-defibrillator.
AB  - The necessity of routine invasive implantable cardioverter-defibrillator (ICD)
      testing before hospital discharge was analyzed in 268 patients. In 98% of the
      patients, invasive ICD testing was not necessary if a preimplant
      electrophysiologic test was performed; most of the observed problems can be
      solved by noninvasive control.

PMID- 9555789
TI  - Successful percutaneous extraction of pacemaker leads with a novel (VascoExtor)
      pacing lead removal system.
AB  - A new pacing lead extraction system (VascoExtor, VascoMed, Germany) with a
      universally applicable locking stylet was used over a period of 12 months to
      extract 25 permanent pacemaker leads (mean implantation time 3.9 +/- 3.8 years)
      in 16 patients who had pacemaker infection (n = 13), lead dysfunction (n = 2), or
      before an automatic defibrillator implant (n = 1). With use of this system, we
      were able to successfully and safely remove 24 of 25 chronic pacing leads (96%)
      in 15 of 16 patients (93%) with sole use of the locking stylet in 81%, and with
      use of an array of ancillary tools in the remaining 19% of patients.

PMID- 9555790
TI  - Pressure ulcers.
AB  - Pressure ulcers are localized areas of tissue necrosis that result from
      unrelieved pressure. They are graded or staged according to the degree of tissue
      damage observed. The main etiologic factors include pressure, shearing forces,
      friction, and moisture. The clinical course may be complicated by several
      conditions including infection, sepsis, osteomyelitis, fistulas, and carcinoma.
      Preventive measures in persons at risk can significantly reduce the incidence of
      pressure ulcers. Successful management should address the four etiologic factors
      as well as the general condition of the patient.

PMID- 9555791
TI  - Omega-3 fatty acid-based lipid infusion in patients with chronic plaque
      psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter
      trial.
AB  - BACKGROUND: Profound changes in the metabolism of eicosanoids with increased
      concentrations of free arachidonic acid (AA) and its proinflammatory metabolites
      have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may
      compete with liberated AA and result in an antiinflammatory effect. OBJECTIVE:
      Our purpose was to assess the efficacy and safety of intravenously administered
      fish-oil-derived lipid emulsion on chronic plaque-type psoriasis. METHODS: A
      double-blind, randomized, parallel group study was performed in eight European
      centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis
      with a severity score of at least 15 according to the Psoriasis Area and Severity
      Index (PASI) participated in a 14-day trial. They were randomly allocated to
      receive daily infusions with either a omega-3 fatty acid-based lipid emulsion
      (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA);
      43 patients) or a conventional omega-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1
      gm/100 ml; 40 patients). The groups were well matched with respect to demographic
      data and psoriasis-specific medical history. Efficacy of therapy was evaluated by
      changes in PASI, in an overall assessment of psoriasis by the investigator, and a
      self-assessment by the patient. In one center neutrophil 4- versus 5-series
      leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were
      investigated and plasma-free fatty acids were determined. RESULTS: The total PASI
      score decreased by 11.2 +/- 9.8 in the omega-3 group and by 7.5 +/- 8.8 in the
      omega-6 group (p = 0.048). In addition, the omega-3 group was superior to the
      omega-6 group with respect to change in severity of psoriasis per body area,
      change in overall erythema, overall scaling and overall infiltration, as well as
      change in overall assessment by the investigator and self-assessment by the
      patient. Response (defined as decrease in total PASI of at least 50% between
      admission and last value) was seen in 16 of 43 patients (37%) receiving the omega
      3 emulsion and 9 of 40 patients (23%) receiving omega-6 fatty acid-based lipid
      emulsion. No serious side effects were observed. Within the first few days of
      omega-3 lipid administration, but not in the omega-6 supplemented patients, a
      manifold increase in plasma-free EPA concentration, neutrophil leukotriene B5 and
      platelet thromboxane B3 generation occurred. CONCLUSION: Intravenous omega-3
      fatty acid administration is effective in the treatment of chronic plaque-type
      psoriasis. This effect may be related to changes in inflammatory eicosanoid
      generation.

PMID- 9555792
TI  - "Rush" skin biopsy specimens in a tertiary medical center: diagnostic yield and
      clinical utility.
AB  - BACKGROUND: Skin biopsy specimens are submitted for "rush" or "stat" processing,
      thereby indicating a sense of urgency about the clinical situation. OBJECTIVE:
      Our purpose was to determine the patient population who underwent biopsy on a
      "rush" basis and assess the way in which interpretation of the skin biopsy
      specimen influences clinical management. METHODS: A retrospective study was
      performed on the "rush" biopsy specimens sequentially requested during 1 year.
      Histologic findings, the clinical situation, and the effect of the biopsy result
      on clinical management were determined. RESULTS: A total of 90 adult patients,
      many critically ill, were identified. The majority of patients were admitted to
      hematology-oncology services (58%). The other 42% were admitted to a variety of
      clinical services. The chief clinical concerns in hematology-oncology patients
      were graft-versus-host disease and cutaneous infection. Only 5.5% of biopsy
      specimens taken to exclude graft-versus-host disease were used in immediate
      clinical decision-making compared with 45% of biopsy specimens for oncology
      patients with suspected infection and 42% for all other services. CONCLUSION:
      Many urgent skin biopsy specimens were not used for immediate clinical decision
      making. The usefulness of skin biopsy varies with the clinical situation, and
      some situations are more prone to yield equivocal histologic data. Knowledge of
      these situations may reduce the number of unhelpful biopsy specimens. Therapy
      based on clinical findings had often been initiated before receiving the biopsy
      results, but biopsy findings are often helpful as confirmatory data. Diagnostic
      findings were not necessary for a biopsy specimen to provide useful data and
      nonspecific findings interpreted in light of clinical findings were also useful.

PMID- 9555793
TI  - Abnormal IgG cardiolipin antibody titers in patients with Raynaud's phenomenon
      and/or related disorders: prevalence and clinical significance.
AB  - BACKGROUND: The prevalence of antibodies to cardiolipin (a-CL) in patients with
      Raynaud's phenomenon (RP) and/or related disorders (rD) is not known. OBJECTIVE:
      The purpose of this study was to determine the prevalence of these antibodies.
      METHODS: We assayed IgG a-CL in 230 consecutive patients with RP/rD and compared
      the results with those in a series of 230 control blood donors. RESULTS: Sixteen
      percent of patients were a-CL positive versus 7.8% of the control donors (p =
      0.014). The prevalence of a-CL positivity was 8.7% for primary RP, 10.5% for
      secondary RP, 8% for chilblains, 25% for essential acrocyanosis, 20% for
      connective tissue diseases, and 17% for undifferentiated connective tissue
      diseases. Among patients with digital necrosis, 24% were a-CL positive.
      CONCLUSION: The prevalence of abnormal a-CL titers is higher in patients with
      RP/rD than in control donors, especially in patients with a connective tissue
      disease.

PMID- 9555794
TI  - A randomized trial of acidified nitrite cream in the treatment of tinea pedis.
AB  - BACKGROUND: Nitric oxide is continually released from normal skin and has
      antimicrobial effects. An acidified nitrite cream releases supraphysiologic
      concentrations of nitric oxide and is fungicidal in vitro. OBJECTIVE: The purpose
      of this study was to assess the efficacy of an acidified nitrite cream as
      treatment for tinea pedis. METHODS: Sixty patients were recruited with both a
      clinical diagnosis of tinea pedis and hyphae identified on direct microscopy;
      they were randomly placed into an active group treated with twice-daily
      application of a mixture of 3% salicylic acid in aqueous cream and 3% nitrite in
      aqueous cream for 4 weeks and a control group treated with 3% salicylic acid in
      aqueous cream and aqueous cream alone. Nineteen patients completed the trial in
      the active group and 16 patients in the control group. Mycologic cure (negative
      results on microscopy and culture) and clinical improvement were measured at 0,
      2, and 4 weeks and after a 2-week interval with no treatment. RESULTS: At the end
      of the treatment period, 18 of the 19 patients in the active group were
      mycologically cured as were 11 of 16 in the control group (p = 0.042). Two weeks
      after the cessation of treatment, 13 of 19 patients in the active group were
      mycologically cured and 5 of 16 in the control group (p = 0.028). The initial
      clinical scores in the active and control groups were 8.1 and 8.19 (two-tailed p
      = 0.95). At 4 weeks they were 1.66 and 6.0 (two-tailed p = 0.002) and after 2
      weeks with no treatment 1.45 and 7.4 (two-tailed p < 0.0002). CONCLUSION:
      Acidified nitrite is effective therapy for tinea pedis.

PMID- 9555795
TI  - Low-dose low-molecular-weight heparin (enoxaparin) is beneficial in lichen
      planus: a preliminary report.
AB  - BACKGROUND: Low-dose heparin devoid of anticoagulant activity inhibits T
      lymphocyte heparanase activity, which is crucial in T-cell migration to target
      tissues. OBJECTIVE: The purpose of this study was to assess the efficacy of low
      dose enoxaparin (Clexane), a low-molecular-weight heparin, as monotherapy in
      lichen planus. METHODS: Included in the study were 10 patients with widespread
      histopathologically proven lichen planus (LP) associated with intense pruritus of
      several months' duration. Patients were given 3 mg enoxaparin, subcutaneously
      once weekly; three patients received four injections, and seven patients received
      six injections. RESULTS: In nine patients the itch disappeared within 2 weeks.
      Within 4 to 10 weeks in eight of these patients, there was complete regression of
      the eruption with residual postinflammatory hyperpigmentation; in one patient,
      there was marked improvement. In one patient, no effect was observed. Of the four
      patients who also had oral LP, only one showed improvement. No side effects were
      observed in any of the patients. CONCLUSION: These findings indicate that
      enoxaparin may be a simple, effective treatment for cutaneous LP.

PMID- 9555796
TI  - Coexistence of lupus erythematosus and porphyria cutanea tarda in fifteen
      patients.
AB  - BACKGROUND: Lupus erythematosus (LE) and porphyria cutanea tarda (PCT) may have
      similar clinical presentations, and their coexistence presents special problems
      in diagnosis and management. OBJECTIVE: The purposes of this study were to
      describe a patient with discoid LE and PCT and to present a review of 15 patients
      with coexistent LE (all variants) and PCT. METHODS: The medical records of all
      patients with coexistent LE and PCT seen between 1976 and 1995 were
      retrospectively reviewed. RESULTS: Of 6179 cases of LE and 676 cases of porphyria
      (all variants), there were 15 patients, 6 men and 9 women, with coexistent LE and
      PCT. The mean age at diagnosis of LE was 42.8 years and of PCT was 48 years. Nine
      patients had discoid LE; five patients had systemic LE, and one patient had
      subacute cutaneous LE. The initial diagnosis was LE in eight patients, PCT in
      five patients, and simultaneous LE and PCT in two patients. Precipitating factors
      for PCT included alcohol in seven patients, iron overload in one patient, and
      estrogen in one patient. Treatment of LE with hydroxychloroquine 200 mg daily
      precipitated PCT in two patients. Patients were treated with phlebotomy or low
      dose antimalarials for PCT. Patients with systemic LE received systemic
      glucocorticoid therapy. Patients with discoid LE and subacute cutaneous LE were
      treated with topical glucocorticoids. CONCLUSION: The association of LE and PCT
      poses therapeutic challenges. The preferred treatment for one may exacerbate the
      other. Use of standard dose antimalarials for LE is inadvisable, and phlebotomy
      or low-dose antimalarials should be used cautiously in patients with coexistent
      disease.

PMID- 9555797
TI  - Single hair grafting for the treatment of vitiligo.
AB  - BACKGROUND: Vitiligo is a disease of unknown cause, and many medical and surgical
      therapeutic methods are used to treat it. OBJECTIVE: Our purpose was to evaluate
      the effectiveness of single hair grafting in patients with vitiligo. METHODS:
      Single hairs were grafted into vitiliginous areas of 21 patients. The diameter of
      the spreading pigmentation was evaluated periodically. RESULTS: Perifollicular
      repigmentation around the grafted hair was observed in 15 patients (71%) within 2
      to 8 weeks. The diameter of the spreading pigmentation ranged from 2 to 10 mm
      during a 12-month follow-up period. In cases of generalized vitiligo,
      perifollicular pigmentation was seen in one of four patients (25%), whereas it
      was observed in 14 of 17 patients (82%) with localized/segmental vitiligo.
      Transformation of depigmented hairs into pigmented ones occurred in five
      patients. CONCLUSION: Single hair grafting appears to be an effective method for
      treating localized/segmental vitiligo, especially on hairy parts of the skin,
      including the eyelids and eyebrows, and for small areas of vitiligo.

PMID- 9555798
TI  - Successful monotherapy of severe and intractable atopic dermatitis by
      photopheresis.
AB  - BACKGROUND: Patients with chronic atopic dermatitis can become unresponsive to
      standard immunosuppressive therapy and thus pose a serious therapeutic problem.
      OBJECTIVE: Our purpose was to evaluate the therapeutic effectiveness of
      photopheresis in the management of patients with severe and intractable atopic
      dermatitis. METHODS: Photopheresis was used as monotherapy in patients (n = 3)
      who previously did not respond to treatment with glucocorticosteroids,
      cyclosporine, phototherapy, or photochemotherapy. Patients were treated at 2-week
      intervals (total number of treatments = 10). RESULTS: In all patients,
      photopheresis induced clinical improvement and reduction of elevated serum levels
      of eosinophil cationic protein and total IgE. Prolongation of the intervals
      between treatments from 2 to 4 weeks caused worsening in one patient, whereas
      shortening of treatment-free intervals improved both clinical and laboratory
      findings. CONCLUSION: These studies indicate that photopheresis may be used as
      monotherapy for the treatment of patients with severe atopic dermatitis that has
      become intractable to standard therapeutic modalities.

PMID- 9555799
TI  - High-dose UVA1 therapy for atopic dermatitis: results of a multicenter trial.
AB  - BACKGROUND: The results of an open, single-center study suggested that
      phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective
      for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE: The purpose
      of this study was to assess the effectiveness of high-dose UVA1 phototherapy for
      acute, severe AD in a randomized multicenter trial in direct comparison with
      topical glucocorticoid therapy. METHODS: Patients were treated with high-dose
      UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1
      x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema
      dose-dependent; n = 16). RESULTS: With a clinical scoring system, significant
      differences in favor of high-dose UVA1R and fluocortolone therapy were observed
      (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was
      superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil
      cationic protein and the blood eosinophil count were significantly reduced after
      high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION: This study
      confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for
      treatment of severe exacerbations of AD.

PMID- 9555801
TI  - Clinically significant drug interactions in dermatology.
AB  - Access to information on clinically significant drug interactions is not readily
      available. This can be a source of uncertainty, and locating this information can
      be tedious and time-consuming. The pharmacology of drug interactions is briefly
      discussed. The most common drug interactions involve altered hepatic metabolism.
      At least 26 drugs are such frequent offenders that they can be considered "red
      flag" drugs. In addition, an extensive list of current significant and less
      significant drug interactions of particular importance to the dermatologist is
      presented.

PMID- 9555800
TI  - Regression of Kaposi's sarcoma during therapy with HIV-1 protease inhibitors: a
      prospective pilot study.
AB  - BACKGROUND: Early studies using HIV protease inhibitors (PI) showed regression of
      Kaposi's sarcoma (KS) lesions in some patients. OBJECTIVE: Our purpose was to
      determine prospectively the influence of PI on HIV-related KS. METHODS: KS
      lesions of nine patients with progressive cutaneous disease were prospectively
      evaluated clinically and by means of epiluminescence microscopy before and during
      PI therapy. HIV viremia and CD4 cell count were measured in parallel. RESULTS:
      All patients experienced reduction or initial stabilization of KS lesions during
      the first 4 to 8 weeks of HIV-1 PI therapy. After a median follow-up of 7 months
      and according to AIDS Clinical Trials Groups criteria, six patients had a partial
      response, two showed stable disease, and in one noncompliant patient KS
      progressed, requiring chemotherapy. With epiluminescence microscopy, a reduction
      in skin surface alterations, lesional size, and color intensity was demonstrated
      in six of nine patients. PI induced a median decrease in viremia of 1.66 log and
      a median increase in the CD4 count of 49 cells/mm3. CONCLUSION: In this series,
      HIV PI therapy reduced or stabilized KS. The efficacy of HIV-1 PI in KS may
      result from the improvement in cellular immunity. These results suggest the use
      of PI in AIDS-related KS regardless of the level of CD4 lymphocyte count and HIV
      viremia.

PMID- 9555802
TI  - Surgical pearl: lubricating jelly as a dressing in punch grafts for pitted acne
      scars.

PMID- 9555803
TI  - Aleukemic leukemia cutis in a patient with acute lymphoblastic leukemia.

PMID- 9555804
TI  - Follicular mucinosis in association with squamous cell carcinoma of the tongue.

PMID- 9555806
TI  - Microbiology of infected eczema herpeticum.

PMID- 9555805
TI  - A case of cicatricial pemphigoid with simultaneous IgG autoantibodies against the
      180 kd bullous pemphigoid antigen and laminin 5.

PMID- 9555807
TI  - Systemic plasmacytosis with cutaneous manifestations in a white man: successful
      therapy with cyclophosphamide/prednisone.

PMID- 9555809
TI  - Linear lichen planopilaris of the face.

PMID- 9555808
TI  - The null allele of GSTM1 does not affect susceptibility to solar keratoses in the
      Australian white population.

PMID- 9555810
TI  - A novel childhood pemphigus vegetans variant of intraepidermal neutrophilic IgA
      dermatosis.

PMID- 9555811
TI  - Acquired syphilis II in early childhood: reappearance of syphilis brephotrophica.

PMID- 9555812
TI  - Fixed food eruption caused by lentils.

PMID- 9555813
TI  - Eosinophilic pustular folliculitis induced by carbamazepine.

PMID- 9555814
TI  - Sign of Leser-Trelat and mycosis fungoides.

PMID- 9555815
TI  - Insect repellents: an overview.

PMID- 9555816
TI  - Insect repellents.

PMID- 9555817
TI  - Dermatoses of the glans penis: penile venereal edema.

PMID- 9555818
TI  - Hepatitis C virus infection in patients with urticaria.

PMID- 9555819
TI  - Topical treatment of acne vulgaris: retinoids and cutaneous irritation.

PMID- 9555820
TI  - Reduced skin irritation with tretinoin containing polyolprepolymer-2, a new
      topical tretinoin delivery system: a summary of preclinical and clinical
      investigations.
AB  - Novel tretinoin cream and gel formulations have been developed that incorporate
      polyolprepolymer-2, which is a material designed to help retain drug molecules in
      and on the skin when applied in topical vehicles. The results of preclinical and
      clinical investigations have confirmed the beneficial impact of such a vehicle on
      tretinoin tolerability. In vitro studies with selected polyolprepolymer
      containing formulations have reduced initial and cumulative tretinoin
      percutaneous penetration, and guinea pig studies showed that the gel formulation
      containing polyolprepolymer-2 caused less erythema and edema than did the
      corresponding commercially-available tretinoin gel formulation. Human studies
      with tretinoin containing polyolprepolymer-2 have consistently demonstrated a
      favorable tolerability profile when compared with commercially-available
      tretinoin. Use of the polyolprepolymer-2-containing tretinoin formulation in
      human studies has resulted in reductions in peeling--a problem commonly
      associated with use of standard tretinoin formulations. These reductions in
      irritation have not been at the expense of efficacy; acne clinical trial results
      indicate comparable effectiveness between tretinoin containing polyolprepolymer2
      and commercially-available tretinoin.

PMID- 9555821
TI  - Irritation potential of a new topical tretinoin formulation and a commercially
      available tretinoin formulation as measured by patch testing in human subjects.
AB  - BACKGROUND: A novel tretinoin preparation uses polyolprepolymer-2, a compound
      designed to reduce skin irritation by helping retain drugs on and in the surface
      layers of the skin. OBJECTIVE: We used patch testing to measure the effect of
      polyolprepolymer-2 on tretinoin-associated irritation. METHODS: Two patch test
      studies were conducted. The first assessed the effect of polyolprepolymer-2 by
      comparing commercially-available tretinoin formulations with respective
      polyolprepolymer-containing formulations of 0.025% tretinoin gel and 0.025%,
      0.05%, and 0.1% tretinoin creams. The second assessed the effect of the
      polyolprepolymer-2 concentration on the potential decrease in irritation by
      comparing: (1) a commercially-available tretinoin cream with prototype tretinoin
      creams containing 20% polyolprepolymer-2 at three different concentrations of
      tretinoin (0.025%, 0.05%, and 0.1%); and (2) the effect of three different
      polyolprepolymer-2 concentrations (10%, 15%, and 20%) in prototype tretinoin
      creams on cumulative irritation. Patch agents were assigned to subjects according
      to a randomization schedule, and during a period of 5 days each subject received
      three 24-hour exposures to the test materials. Twenty-four hours elapsed between
      old patch removal and new patch application. RESULTS: In the first study, the
      tretinoin gel and cream containing polyolprepolymer-2 caused significantly less
      irritation than all equivalent formulations of the commercially-available
      tretinoin gel and creams except the 0.025% cream formulation. Irritation scores
      were not significantly different in terms of irritation in the 0.025% creams
      although scores did indicate a trend towards lower irritation with 0.025%
      tretinoin cream containing polyolprepolymer-2. In the second study, the tretinoin
      gel containing polyolprepolymer-2 and the three tretinoin prototype creams also
      containing polyolprepolymer-2 caused significantly less irritation than
      comparable concentrations of the commercially-available tretinoin. In addition,
      the 0.025% tretinoin gel formulation containing polyolprepolymer-2 was no more
      irritating than the commercially-available 0.025% tretinoin cream. CONCLUSION:
      Tretinoin formulations containing polyolprepolymer-2 are, in general, less
      irritating than the currently marketed tretinoin formulations.

PMID- 9555822
TI  - Comparative efficacy and safety of two 0.025% tretinoin gels: results from a
      multicenter double-blind, parallel study.
AB  - BACKGROUND: The addition of polyolprepolymer-2 in tretinoin formulations may
      reduce tretinoin-induced cutaneous irritation. OBJECTIVE: This study compared the
      efficacy and safety of a new 0.025% tretinoin gel containing polyolprepolymer-2,
      its vehicle, and a commercially-available 0.025% tretinoin gel in patients with
      mild to moderate acne vulgaris. METHODS: In this 12-week multicenter, double
      blind, parallel group study, efficacy was evaluated by objective lesion counts
      and the investigators' global evaluations. Subjective assessment of cutaneous
      irritation by the investigators and patients evaluated safety. RESULTS: The
      efficacy of the two active treatments in this 215 patient study was comparable,
      and both treatments were statistically significantly more effective than vehicle.
      When compared with the commercially-available tretinoin gel, the formulation
      containing polyolprepolymer-2 demonstrated statistically significantly less
      peeling at days 28, 56, and 84, statistically significantly less dryness by day
      84, and statistically significantly less itching at day 14. Irritation scores for
      the formulation containing polyolprepolymer-2 were numerically lower but not
      statistically different from those of the commercially-available gel for erythema
      and burning. The number of cutaneous and noncutaneous adverse events were similar
      for both active medications. CONCLUSION: The two 0.025% gels studied demonstrated
      comparable efficacy. However, the gel formulation containing polyolprepolymer-2
      caused significantly less peeling and drying than the commercially-available
      formulation by day 84 of the study.

PMID- 9555823
TI  - Double-blind, vehicle-controlled, multicenter comparison of two 0.025% tretinoin
      creams in patients with acne vulgaris.
AB  - BACKGROUND: Preclinical study and human patch tests indicate polyolprepolymer-2
      may reduce cutaneous tretinoin-induced irritation. OBJECTIVE: This study compared
      the clinical efficacy and safety of a 0.025% tretinoin cream containing
      polyolprepolymer-2 and its vehicle to a commercially-available 0.025% tretinoin
      cream. METHODS: In this 12-week multicenter, double-blind, parallel group study
      in patients with mild to moderate acne, objective lesion counts and the
      investigators' global evaluations evaluated efficacy. Subjective evaluations of
      skin irritation were used to study safety. RESULTS: A total of 271 patients were
      enrolled. The active treatments demonstrated comparable efficacy that was
      statistically significantly greater than that of the vehicle. Safety evaluations
      of cutaneous and noncutaneous adverse events also indicated comparable results of
      the active treatments. CONCLUSION: The commercially-available 0.025% tretinoin
      cream and the 0.025% tretinoin cream containing polyolprepolymer-2 demonstrated
      comparable efficacy and safety.

PMID- 9555824
TI  - Mergers, acquisitions, and trauma care in the 1990s.

PMID- 9555825
TI  - Measuring injury severity: time for a change?
AB  - BACKGROUND: The Injury Severity Score (ISS) does not take into account multiple
      injuries in the same body region, whereas a New ISS (NISS) may provide a more
      accurate measure of trauma severity by considering the patient's three greatest
      injuries regardless of body region. The purpose of this study was to evaluate the
      ISS and NISS in patients with blunt trauma. METHODS: Consecutive individuals
      treated from January of 1992 to September of 1996 at one institution were
      included if they had sustained blunt trauma and satisfied triage standards (n =
      2,328). For each patient, we computed the ISS and the NISS to determine how often
      the two scores were identical or discrepant. Discrepant cases were then further
      analyzed using receiver operating characteristic curves to determine which score
      better predicted short-term mortality. RESULTS: The mean ISS was 25 +/- 13, and
      the mean NISS was 33 +/- 18. The two predictive scores were identical in 32% of
      patients and discrepant in 68% of patients. Patients with identical scores had a
      lower mortality rate than patients with discrepant scores (10% vs. 13%; p <
      0.02). In patients with discrepant scores, the area under the receiver operating
      characteristic curves was greater for the NISS than the ISS (0.852 vs. 0.799; p <
      0.001), and greater amounts of discrepancy were associated with increasing rates
      of mortality (p < 0.001). CONCLUSIONS: The NISS often increases the apparent
      severity of injury and provides a more accurate prediction of short-term
      mortality. The benefit associated with using the NISS rather than the ISS must be
      weighed against the disadvantages of changing a scoring system and the potential
      for still greater improvements.

PMID- 9555826
TI  - Changes in red cell transfusion practice among adult trauma victims.
AB  - BACKGROUND: Recent attention concerning the adverse outcomes of blood transfusion
      has resulted in decreased blood product usage for nonemergency care. We
      hypothesized that there has also been a decrease in blood product use in the
      management of seriously injured adults. METHODS: A retrospective review of
      institutional database records was conducted at a regional trauma center for
      adults admitted during 1991, 1993, and 1995. Data was analyzed for trends in
      amount, type, and timing of blood product use. RESULTS: A total of 1,738 patients
      were assessed, with 1,605 meeting inclusion. The three patient groups were
      similar, including injury severity (overall mean Injury Severity Score of 23.6),
      mechanism (88% blunt), and survival (87%). In 1991, 54% of the patients were
      transfused a total of 2,341 units of packed red blood cells (mean 4.67 units/pt
      treated) versus 42% of patients in 1995 (p < 0.0001) who received 2,018 packed
      red blood cells (mean 3.57 units/patient treated, p = 0.05). A significantly
      higher proportion of units was transfused in the first 24 hours of care in 1995
      (64%) compared with 1991 (21%, p < 0.0001). A reduction in the use of universal
      donor type-O blood use was also found (1.21 vs. 0.65 units/patient transfused, p
      < 0.0001). Despite similar admission hemoglobin concentrations (124.1 vs. 125.3,
      not significant), significant reductions were found in the average 24-hour (109.2
      vs. 103.8, p < 0.001), lowest (96.5 vs 92.1, p < 0.01) and discharge (115.8 vs.
      110.5, p < 0.001) concentrations. CONCLUSIONS: Between 1991 and 1995 there have
      been significant reductions in both the number of trauma patients receiving blood
      products and the total number of units transfused. These findings may reflect
      lower or abandoned hemoglobin transfusion triggers and increased awareness of
      complications related to transfusion.

PMID- 9555827
TI  - Effect of the Advanced Trauma Life Support program on medical students'
      performance in simulated trauma patient management.
AB  - BACKGROUND: Part of the senior medical students' examination at the University of
      Toronto involves testing with simulated patient management. We compared the
      performance in these simulations of senior medical students who received Advanced
      Trauma Life Support (ATLS) training with those who did not receive ATLS training.
      METHODS: Thirty-two students (group I) completed a standard ATLS course, 12
      students (group II) audited the ATLS course, and their performance in the trauma
      simulations was compared with 44 matched control students (group III) from the
      same class. Performance in the nontrauma patient simulation stations was also
      analyzed. The score on each station was standardized to a maximum of 20. The
      students were also graded on overall Approach (scale of 1 to 5) and pass status.
      RESULTS: The mean scores (+/-SD, *p < 0.05 compared with other groups) were as
      follows: Trauma Station, 17.5 +/- 1.02* for group I, 11.76 +/- 0.72* for group
      II, and 14.67 +/- 0.54* for group III; Nontrauma Station, 13.05 +/- 0.95 for
      group I, 12.25 +/- 0.72 for group II, and 11.88 +/- 0.80 for group III; Approach,
      4.45 +/- 0.50* for group I, 2.09 +/- 0.60* for group II, 3.50 +/- 0.67* for group
      III. The ATLS-trained and ATLS-audit students had higher scores in the trauma
      stations than the control group, with the highest scores being in the ATLS
      trained group. All ATLS-trained students passed with 62.5% honors and 37.5%
      passing grades. The ATLS-audit group had 33.3% honors and 66.6% passing grades,
      compared with the control group who had 84.09% pass, 9.09% borderline, and 6.82%
      failure in the trauma stations. CONCLUSIONS: The ATLS course, both complete and
      audit status, prepares students more appropriately for managing trauma patients
      as judged by trauma simulation scenarios. Consideration should be given for
      including ATLS as an integral part of the senior medical student curriculum.

PMID- 9555828
TI  - Hypertonic saline activates lipid-primed human neutrophils for enhanced elastase
      release.
AB  - BACKGROUND: Ongoing clinical trials have revived interest in hypertonic saline
      (HTS) for postinjury resuscitation; these studies have documented serum Na+
      concentrations > or = 170 mmol/L. Recent animal studies have shown that HTS
      enhances T-cell and monocyte function, but effects on the polymorphonuclear
      neutrophil (PMN) remain unclear. The postinjury lipid mediators platelet
      activating factor (PAF) and leukotriene B4 (LTB4) have been implicated in PMN
      priming for cytotoxicity, which is believed to be important in the pathogenesis
      of multiple organ failure. We hypothesized that HTS would stimulate PMN
      superoxide (O2-) and elastase release from PAF- and LTB4-primed PMNs. METHODS:
      Isolated PMNs from five donors were primed for 5 minutes with 200 nmol/L PAF or 1
      micromol/L LTB4 in Kreb's-Ringer's phosphate with dextrose at a Na+ concentration
      of 140 mmol/L (normal serum Na+ concentration), pelleted, and resuspended in
      Kreb's-Ringer's phosphate with dextrose for 10 minutes at a Na+ concentration of
      130 to 170 mmol/L. O2- generation was measured by superoxide dismutase
      inhibitable reduction of cytochrome c and elastase release by cleavage of N
      methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide. RESULTS: HTS with Na+
      concentration up to 170 mmol/L had no significant effect on O2- production or
      elastase release from quiescent cells. Na+ concentration of 160 and 170 mmol/L,
      however, activated PAF- and LTB4-primed PMNs for enhanced elastase release with
      no effect on O2- production. CONCLUSION: In clinically relevant concentrations,
      elevated Na+ activates lipid-primed neutrophils for enhanced elastase
      degranulation. Consequently, the administration of HTS in the early postinjury
      resuscitation period, when PMNs are maximally primed, may activate PMN elastase
      release and thereby promote the development of multiple organ failure.

PMID- 9555829
TI  - Does free fluid on abdominal computed tomographic scan after blunt trauma require
      laparotomy?
AB  - BACKGROUND: Abdominal computed tomographic (CT) scans are used in the evaluation
      of blunt trauma. The purpose of this study was to determine if isolated
      intraperitoneal fluid seen on CT scan necessitates laparotomy. METHODS: Trauma
      registry records of patients who underwent abdominal computed tomography from
      January 1994 through January 1997 were studied. Data were reviewed for age,
      gender, CT scan interpretation, associated injuries, and operative findings.
      RESULTS: Abdominal injury was identified in 126 patients. Seventy-eight patients
      had evidence of solid-organ injury and 17 patients had extraperitoneal injury.
      Isolated intraperitoneal fluid was identified in 31 patients. All patients with
      isolated fluid underwent laparotomy; 29 of these procedures (94%) were
      therapeutic. Bowel injuries occurred in 18 patients and mesenteric injuries in 8
      patients. Five patients had intraperitoneal bladder rupture, and undetected solid
      organ injuries were found in two patients. Other organs injured included the
      stomach, pancreas, ovary, and uterus. CONCLUSION: Exploratory laparotomy was
      therapeutic in 94% of patients. Isolated intraperitoneal fluid on CT scan after
      blunt trauma mandates laparotomy.

PMID- 9555830
TI  - A comparison of sonographic examinations for trauma performed by surgeons and
      radiologists.
AB  - BACKGROUND: It has been demonstrated that surgeons and surgery residents, trained
      in the focused abdominal sonographic examination, are able to accurately and
      reliably evaluate trauma patients. Despite this, radiologists have objected to
      surgeon-performed sonography for several reasons. We set out to compare the
      accuracy of sonographic examinations performed by surgery residents and
      radiologists. METHODS: A retrospective review of medical records of all trauma
      patients who received focused ultrasound examinations from January 1, 1995,
      through June 30, 1996, at one of two American College of Surgeons-verified Level
      I trauma centers in the same city was undertaken. Ultrasound examinations were
      performed by surgery residents at trauma center A (TCA) and by radiologists or
      radiology residents at trauma center B (TCB). Findings for each patient were
      compared with the results of computed tomography, diagnostic peritoneal lavage,
      operative exploration, or observation. Sensitivity, specificity, accuracy,
      positive predictive value, and negative predictive value were calculated for each
      group of patients. Comparison of patient charges for the trauma ultrasound
      examinations at each of the trauma centers was also made. RESULTS: Patient
      populations at the two centers were similar except that the mean Injury Severity
      Score at TCB was higher than at TCA (11.74 vs. 9.6). Sensitivity, specificity,
      accuracy, or negative predictive value were not significantly different between
      the two cohorts. A significantly lower positive predictive value for examinations
      performed by surgery residents was noted and attributed to a lower threshold of
      the surgery residents to confirm their findings by computed tomography. Billing
      data revealed that the average charge for trauma sonography by radiologists (TCB)
      was $406.30. At TCA, trauma sonography did not generate a specific charge;
      however, a $20.00 sum was added to the trauma activation fee to cover ultrasound
      machine maintenance and supplies. CONCLUSION: Focused ultrasound examination in
      the trauma suite can be as safely and accurately performed by surgery residents
      as by radiologists and radiology residents and should be a routine part of the
      initial trauma evaluation process.

PMID- 9555831
TI  - Preferential benefit of implementation of a statewide trauma system in one of two
      adjacent states.
AB  - BACKGROUND: Implementation of Oregon's trauma system was associated with a
      reduction in the risk of death for hospitalized injured patients. An alternative
      explanation for improved outcome, however, is favorable concurrent temporal
      trends, e.g., new technologies and treatments. PATIENTS AND METHODS: To control
      for temporal trends, seriously injured hospitalized patients in Oregon and
      Washington were compared before either state had a trauma system (1985-1988) and
      when only the Oregon trauma system had been implemented (1990-1993). The study
      group consisted of hospitalized injured patients aged 16 to 79 years with one or
      more index injuries in six body regions, i.e., head, chest, spleen/liver, femur
      or pelvis fracture, and burns. Hospital discharge claims data were analyzed,
      converting International Classification of Diseases, Ninth Revision, Clinical
      Modification, discharge diagnosis codes to Abbreviated Injury Scale scores and
      Injury Severity Scores using a conversion algorithm. Multivariate logistic
      regression models were used to estimate the differential risk-adjusted odds of
      death in Oregon compared with Washington after adjustment for demographics,
      injury type, and injury severity. RESULTS: Findings indicated no difference in
      the risk-adjusted odds of death between Oregon and Washington while both states
      functioned under an ad hoc trauma system (1985-1988). A significant reduction in
      the risk of death, however, was noted in Oregon for patients with an index injury
      and an Injury Severity Score > 15 compared with Washington (adjusted odds ratio
      (OR) = 0.80, 95% confidence interval (CI) = 0.70-0.91) after trauma system
      implementation in Oregon (1990-1993). Specifically, reductions in the risk of
      death were demonstrated for patients with head injuries (adjusted OR = 0.70, 95%
      CI = 0.59-0.82) or liver/spleen injuries (adjusted OR = 0.73, 95% CI = 0.54
      0.99). CONCLUSION: Assuming that the two states demonstrated similar concurrent
      temporal trends, the findings support the conclusion that improved outcomes among
      injured patients in Oregon may be attributed to the institution of a statewide
      trauma system.

PMID- 9555832
TI  - Trauma patients 75 years and older: long-term follow-up results justify
      aggressive management.
AB  - BACKGROUND: Long-term survival rate and functional status after trauma for one of
      the fastest growing segments of the population, patients 75 years and older, is
      poorly documented. METHODS: Trauma patients 75 years and older who were
      discharged from our Level I trauma center between June 1988 and July 1992 (n =
      279) were contacted by mail or phone. Public death records were used to identify
      patients who had died. A stepwise logistic regression analysis was performed to
      determine predictors of poor outcome (death within 6 months). Main outcome
      measures included mortality and self-assessed functional status. RESULTS: A
      minimum 4-year follow-up was obtained for 81% of the 279 study patients. The mean
      follow-up period was 5.4 +/- 1.1 years. Mean age at time of injury was 81 +/- 5
      years (range, 75-101 years); mean Injury Severity Score was 9.4 +/- 7.7. At
      follow-up, 132 patients (47%) had died, 93 patients (33%) were contacted, and 54
      patients (19%) could not be located. Twelve percent of patients survived less
      than 6 months after discharge. Poor survival was predicted by preexisting
      diseases (dementia, p = 0.001; hypertension, p = 0.02; and chronic obstructive
      pulmonary disease, p = 0.05) and not by age or severity of injury. The mean age
      of patients still living was 85 +/- 3.9 years (range, 79-99 years), and 77 of 93
      patients were living in an independent setting (33 alone, 44 with spouse or
      family); of these, 57% reported no difficulties in performing 12 of 14 activities
      of daily living. CONCLUSION: Despite higher than expected mortality after
      discharge, aggressive management of trauma patients 75 years and older is
      justified by the favorable long-term outcome.

PMID- 9555833
TI  - Long-term psychosocial adaptation of children who survive burns involving 80% or
      greater total body surface area.
AB  - OBJECTIVE: To examine the psychosocial adjustment of survivors of massive
      pediatric burn injuries, the change in adjustment across time, and the impact on
      parents. BACKGROUND: Patients/parents were assessed at regular intervals postburn
      using standardized tests of adjustment. Patients who could not be included in
      standardized longitudinal assessments were administered questionnaires by
      mail/telephone. METHODS: The Child Behavior Checklist, the Teacher Report Form,
      the Youth Self Report Form, and the Parenting Stress Index were utilized to
      assess adjustment. RESULTS: On all objective measures, the group of survivors and
      their parents were within normal limits. Adjustment neither improved nor
      deteriorated over time. CONCLUSION: Children who survive massive burn injuries
      can achieve positive psychosocial adaptation.

PMID- 9555834
TI  - A prospective study of predictors of disability at 3 months after non-central
      nervous system trauma.
AB  - OBJECTIVE: To delineate which injury-related, demographic, and psychosocial
      variables were predictive of severe disability (limitations in the performance of
      socially defined roles and tasks) at 3 months after discharge from acute
      hospitalization for non-central nervous system traumatic injury. PATIENTS AND
      METHODS: The study design was prospective, longitudinal, and correlational. The
      sample consisted of 109 injured patients at three urban trauma centers. Data were
      obtained from patient interview using the Sickness Impact Profile, the Impact of
      Event Scale, and the Social Support Questionnaire; injury-related data were
      obtained from the medical record and computerized trauma registries. RESULTS: The
      sample had a mean age of 37.4 +/- 16.8 years, a mean number of injuries per
      person of 4.4 +/- 2.8, and a mean Injury Severity Score of 15.5 +/- 9.9. Motor
      vehicle crashes (34.9%) and violent injuries (33%) were the predominant causes of
      injuries. Patients experienced severe levels of disability (Sickness Impact
      Profile, mean = 26.1) and moderate levels of psychological distress (Impact of
      Event Scale, mean = 30.6; intrusion mean = 14.6 and avoidance mean = 16.0). Three
      variables were predictive of severe disability at 3 months: high levels of
      intrusive thoughts (odds ratio, 2.9; 95% confidence interval, 1.1-7.7); injury
      with a maximal Abbreviated Injury Scale score in an extremity (odds ratio, 2.9;
      95% confidence interval, 1.2-6.9); and having not graduated from high school
      (odds ratio, 3.4; 95% confidence interval, 1.2-10). CONCLUSION: Extremity
      injuries, lack of high school graduation, and high level of posttraumatic
      psychological distress with intrusive thoughts are risk factors for severe
      disability at 3 months after discharge from the hospital.

PMID- 9555835
TI  - Psychosocial factors limit outcomes after trauma.
AB  - BACKGROUND: Psychological morbidity compromises return to work after trauma. We
      demonstrate this relationship and present methods to identify risks for
      significant psychological morbidity. METHODS: Thirty-five adults were evaluated
      prospectively for return to functional employment after injury using demographic
      data, validated psychological and health measures, and the Michigan Critical
      Events Perception Scale. Evaluation was conducted at admission and at 1 and 5
      months after injury. RESULTS: Poor return to work at 5 months was attributable to
      physical disability (p < 0.05) and psychological disturbance (p < 0.05) in a
      regression model that controlled for preinjury employment and psychopathologic
      factors as well as injury severity. A high score on the Impact of Events Scale
      administered during acute admission predicted development of acute stress
      disorder at 1 month (p < 0.01, odds ratio (OR) = 9.4) and posttraumatic stress
      disorder at 5 months (p < 0.05, OR = 6.7). Peritraumatic dissociation on the
      Michigan Critical Events Perception Scale was predictive for development of acute
      stress disorder (p < 0.05, OR = 5.8) at 1 month and posttraumatic stress disorder
      (p < 0.05, OR = 7.5) at 5 months. CONCLUSION: Psychological morbidity after
      injury compromises return to work independent of preinjury employment and
      psychopathologic condition, Injury Severity Score, or ambulation. A high Impact
      of Events Scale score or peritraumatic dissociation at admission predicts this
      morbidity.

PMID- 9555836
TI  - Can surgeons evaluate emergency ultrasound scans for blunt abdominal trauma?
AB  - OBJECTIVE: To determine whether surgeons and residents with minimal training can
      evaluate accurately emergency ultrasound (US) examinations compared with
      radiologists for blunt abdominal trauma. METHODS: Over 7 months, we conducted a
      prospective study comparing the evaluation of emergency US for blunt abdominal
      trauma by surgeons and attending radiologists. US readings from the surgical team
      and the radiologists were correlated with outcome. RESULTS: One hundred-twelve
      patients were included in the study. Ninety-two patients had an US read as
      negative by the surgical and radiology services with no subsequent injuries
      identified. Eighteen patients had an US deemed positive by the surgical service
      and radiologists. Injuries were confirmed in this group by operation or computed
      tomography. One patient had an US deemed positive by the surgical team and
      subsequently negative by the radiologist. A diagnostic peritoneal lavage was
      performed which was negative. Another patient had an US interpreted as negative
      by the surgical evaluator and positive by the radiologist. Exploratory laparotomy
      was negative for intraabdominal hemorrhage or organ injury. Overall results
      reveal an accuracy on US reading of 99% for the surgical team and 99% for the
      attending radiologists. CONCLUSION: Surgeons and surgical residents at different
      levels of training can accurately interpret emergency ultrasound examinations for
      blunt trauma from the real-time images, at a level comparable to attending
      radiologists.

PMID- 9555837
TI  - Evaluation of alpine skiing and snowboarding injury in a northeastern state.
AB  - BACKGROUND: To demonstrate the injury patterns of Alpine skiing and snowboarding
      in a northeastern state and evaluate potential risk factors. METHODS: The medical
      records of a single pediatric and adult Level I trauma center were evaluated from
      January 1, 1990, through December 31, 1995. All admissions with injuries caused
      by Alpine skiing or snowboarding were reviewed. Those patients arriving from two
      local ski resorts, all of whose injuries are referred to the institution for
      care, were separated out for consideration. Age, sex, type of injury, date of
      injury, Injury Severity Score, operations performed, and outcome (including
      mortality) were evaluated. In addition, resort utilization for the study period
      was obtained from the two resorts included in the evaluation. Mortality data was
      obtained from the Vermont office of the Chief Medical Examiner for the same time
      period. RESULTS: For the 6-year period of the study approximately 2,978,000 skier
      and snowboarder days were recorded at the study sites. Approximately 447,000 of
      those days were attributed to snowboarders (15%). In all, 279 patients were
      admitted for injuries (0.01%), 238 were related to Alpine skiing (incidence
      0.01%) and 40 to snowboarding (incidence 0.01%). Snowboarders were statistically
      younger (20 years; range, 4-44 years) than skiers (29 years; range, 6-70 years)
      (p < 0.001) and had a significantly lower Injury Severity Score (15 in
      snowboarders vs. 27 in skiers, p < 0.03). Two female patients were injured
      snowboarding and 68 female patients were injured skiing. Eight percent of injured
      snowboarders and 16% of injured skiers sustained multiple injuries (p < 0.01).
      Injury patterns were significantly different. Upper extremity injuries were
      almost exclusively found in snowboarders (24% vs. 7%, p < 0.003), whereas
      cruciate ligament injuries occurred far more commonly in skiers (45% vs. 4%, p <
      0.001 Lower extremity injuries in general were more common in skiers (78% vs.
      38%, p < 0.001). Central nervous system injuries, including head and spine, were
      evenly distributed over the two groups, although the snowboarders with central
      nervous system injuries were younger. In addition, splenic injuries were more
      common in snowboarders (13% vs. 2%, p < 0.01). Snowboarding accidents were far
      more common in December, March, and April than other months. Fifty-one patients
      sustained abdominal or chest injuries and only two of these required operative
      intervention (two splenectomies). Other operative interventions were limited to
      extremity injuries, injuries of the spine, or placement of an intracranial
      pressure monitor. There were no fatalities recorded in this population, although
      over the 6.5 years, there were 25 deaths related to alpine skiing and one to
      snowboarding in the State (incidence 0.0000009 skier days). Victims tended to be
      male: 96% of the skiers and the one snowboarder. The predominant cause of death
      was blunt head trauma followed by blunt chest trauma. Helmets were not worn by
      those sustaining head injuries or fatalities. Spine injuries were recorded only
      in extremely young snowboarders and skiers out of control. CONCLUSION:
      Snowboarders and Alpine skiers are equally prone to injury. Snowboarding
      accidents are typically less severe and show significantly different injury
      patterns than skiing accidents. Abdominal and chest injuries in this population
      are generally amenable to nonoperative management. Prevention programs are best
      targeted at safe skiing and snowboarding practices, not skiing or snowboarding in
      poor conditions, use of helmets for skiers, and restraint of snowboard use in
      very young children.

PMID- 9555838
TI  - Secretory phospholipase A2 cleavage of intravasated bone marrow primes human
      neutrophils.
AB  - BACKGROUND: Recent clinical reports suggest that early femoral intramedullary rod
      (IMR) fixation in patients with multiple injuries increases the risk of adult
      respiratory distress syndrome (ARDS). We have shown that lipid-mediated
      neutrophil (PMN) priming and elevated circulating levels of secretory
      phospholipase A2 (sPLA2) within the first 24 hours after injury correlate with
      the development of ARDS. We thus hypothesized that circulating lipid products,
      generated by sPLA2 cleavage of intravasated bone marrow, prime PMNs for enhanced
      superoxide anion (O2-) production. METHODS: Isolated PMNs from healthy volunteers
      were incubated for 5 minutes with buffer or sPLA2-lysed bone marrow (100 U/mL)
      collected from trauma patients. After formyl-methionyleucylphenylalanine (fMLP)
      activation, O2- production was quantified by the superoxide dismutase-inhibitable
      reduction of cytochrome c. Blood samples were also drawn from five injured
      patients before and 24 hours after femoral IMR fixation. PMNs were isolated and
      assessed for in vivo priming. RESULTS: PMNs incubated with sPLA2-lysed bone
      marrow were primed for more than 3.5 times greater fMLP-induced O2- production.
      Furthermore, in patients with femoral fractures, PMN O2- release in response to
      fMLP after IMR fixation was more than 2.5 times higher than before fixation.
      CONCLUSION: Collectively, the findings suggest that bone marrow released from
      acute fracture sites may become a lipid substrate for the elevated sPLA2 levels
      found in injured patients. The resultant priming of PMNs may thus render the
      injured patient at risk for ARDS. Although clearly hypothetical at present, we
      submit that these observations warrant further investigation because of their
      clinical implications.

PMID- 9555839
TI  - Early combined management of frontal sinus and orbital and facial fractures.
AB  - BACKGROUND: Historically, frontal sinus fractures and associated maxillofacial
      fractures were addressed at different times. We retrospectively reviewed our
      experience with a series of 79 consecutive patients with bitable frontal sinus
      fractures, most with associated facial fractures, who underwent early combined
      cranial and maxillofacial procedures. METHODS: The operations were performed
      emergently for patients with open or depressed skull fractures and hematomas with
      mass effect, and electively within 2 weeks for those with closed fractures. The
      cranial procedures were performed first. The nasofrontal ducts were packed with
      "cigars" of bacitracin powder wrapped in Surgicel. All patients received
      antibiotics for 2 weeks. RESULTS: Postoperatively, good subjective cosmetic
      results were obtained except in one patient. Eight patients with lumbar drains
      had expected temporary cerebrospinal fluid (CSF) leaks of less than 72 hours
      duration. Six postoperative intracranial infections (four cases of meningitis,
      one epidural empyema, and one intracerebral abscess) were detected; five of these
      occurred in patients with open depressed fractures. Patients with preoperative
      CSF leaks (p = 0.0039, Fisher's exact test) and open fractures (p = 0.065,
      Fisher's exact test) were more likely to develop intracranial infections.
      CONCLUSION: The combined neurosurgical and maxillofacial repairs achieved good
      cosmetic outcomes, with relatively low morbidity. By combining the two-stage
      procedure into one stage, standard surgical and anesthetic risks could
      potentially be reduced. Preoperative CSF leaks and open fractures were associated
      with a higher incidence of postoperative central nervous system infection. Early
      operations did not appear to be associated with a higher complication rate.

PMID- 9555840
TI  - Fractures of the greater tuberosity presenting as rotator cuff abnormality:
      magnetic resonance demonstration.
AB  - BACKGROUND: To show that magnetic resonance imaging (MRI) can be useful to
      diagnose radiographically invisible greater tuberosity fractures in patients with
      clinical presentations suspicious for rotator cuff injury. METHODS: Six patients
      with subtle greater tuberosity fractures who were sent for MRI because of
      possible rotator cuff tear are reviewed (age range, 27-51 years; mean, 40.5 +/-
      8.4 years). Five of the patients recount direct trauma to their shoulders,
      whereas one noticed shoulder pain after a fall in which she fractured her ankle.
      RESULTS: MRI showed an area of edema confined to the greater tuberosity with
      linear low signal extending through the tuberosity consistent with a fracture in
      all cases. Although five patients had a complete set of shoulder radiographs
      before MRI, these were interpreted as normal in all cases. Full-thickness rotator
      cuff tears were not present in any of the cases. All of the patients were treated
      conservatively with good results. CONCLUSIONS: MRI can prevent unnecessary
      arthroscopy in patients clinically suspected of rotator cuff damage by showing
      subtle fractures of the greater tuberosity not visible on radiographs.

PMID- 9555841
TI  - Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a
      study of bone mineral density and torsional strength on rabbits.
AB  - We investigated the effect of intermittent hyperbaric oxygen (HBO) therapy on the
      bone healing of tibial lengthening in rabbits. Twelve male rabbits were divided
      into two groups of six animals each. The first group went through 2.5 atmospheres
      absolute of hyperbaric oxygenation for 2 hours daily, and the second group did
      not go through hyperbaric oxygenation. Each animal's right tibia was lengthened 5
      mm using an uniplanar lengthening device. Bone mineral density (BMD) study was
      performed for all of the animals at 1 day before operation and at 3, 4, 5, and 6
      weeks after operation. All of the animals were killed at 6 weeks postoperatively
      for biomechanical testing. Using the preoperative BMD as an internal control, we
      found that the BMD of the HBO group was increased significantly compared with the
      non HBO group. The mean %BMD at 3, 4, 5, and 6 weeks were 69.5%, 80.1%, 87.8%,
      and 96.9%, respectively, in HBO group, whereas the mean %BMD were 51.6%, 67.7%,
      70.5%, and 79.2%, respectively, in non-HBO group (two tailed t test, p < 0.01, p
      < 0.01, p < 0.01, and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). Using the
      contralateral nonoperated tibia as an internal control, we found that torsional
      strength of lengthened tibia of the HBO group was increased significantly
      compared with the non-HBO group. The mean percent of maximal torque was 88.6% in
      HBO group at 6 weeks, whereas the mean percent of maximal torque was 76.0% in non
      HBO group (two-tailed t test, p < 0.01). The results of this study suggest that
      the bone healing of tibial lengthening is enhanced by intermittent hyperbaric
      oxygen therapy.

PMID- 9555842
TI  - Value of routine angiography before traumatic lower-limb reconstruction with
      microvascular free tissue transplantation.
AB  - From November 1993 to June 1997, long-bone defects in 40 trauma patients were
      reconstructed with free osteoseptocutaneous fibula flaps. To determine the
      necessity of routine angiography in traumatized lower limbs before free flap
      transplantation, a prospective study was carried out. The study subjects were 34
      patients, 25 males and 9 females, with an average age of 40.6 years.
      Reconstruction was performed primarily for bone defects after Gustillo type III b
      open fractures in 17 patients and secondarily for malunion and osteomyelitis in
      17 patients. Reconstructed bone defects included 25 tibias and 9 femurs. Normal
      pedal pulses were palpable in 31 patients. Angiographic findings were abnormal in
      seven patients. In the three patients with abnormal pedal pulses, the particular
      nonpalpable pulses correlated with the vascular lesions shown in the angiograms
      (one in the tibial anterior artery and two in the tibial posterior artery). Four
      patients with either injury of the peroneal artery (three cases) or
      pseudoaneurysm of the tibial anterior artery (one case) had normal pedal pulses.
      In all patients, microvascular transplantations were performed successfully. Our
      study demonstrates the importance of thorough clinical evaluation. Preoperative
      angiography of the injured lower limbs did not provide relevant additional
      informations in this series. Familiarity with all available techniques makes it
      possible to cope with almost any difficult posttraumatic vascular condition.
      Routine recipient-site angiography before microsurgical reconstruction,
      therefore, seems unjustified.

PMID- 9555843
TI  - Simulation program for optimal orthopedic call: a modeling system for orthopedic
      surgical trauma call.
AB  - This report uses a mathematical modeling system to define optimal orthopedic
      coverage for trauma centers. Data from 2,325 patients treated with emergency
      orthopedic operations within 24 hours of admission at 78 randomly sampled and at
      four totally sampled verified centers were used to create a profile of (1)
      admission by month, day, and hour; (2) operation times; and (3) operation
      duration. The reason for operation included (1) open fracture or crush (809
      patients); (2) irreducible dislocations (164 patients); (3) fracture with
      vascular injury (seven patients); (4) dislocation with vascular injury (17
      patients); (5) compartment syndrome (11 patients); (6) femoral neck fracture in
      young patients (36 patients); (7) combination of categories 1 to 6 (70 patients);
      (8) fracture with multiple injuries (171 patients); and (9) urgent not emergent
      (1,040 patients). The program defined the frequency that an injured patient
      needing an orthopedic consult would wait beyond 30 minutes because the orthopedic
      surgeon was doing a trauma related operation at a center with one or two
      orthopedic surgeons on call. The probability that a patient cannot be seen
      promptly by one orthopedic surgeon in a center doing 25, 50, 75, 100, 200, and
      300 emergency procedures per year is 0.17, 0.74, 1.6, 3.1, 12.5, and 28 patients
      per year. When two are on call, 1.3 patients, yearly, will wait more than 30
      minutes in a center doing 300 emergency procedures. Thus, mandatory orthopedic
      backup call for a trauma center performing fewer than 100 emergent trauma
      procedures within 24 hours is unwarranted.

PMID- 9555844
TI  - Selective application of laparoscopy and fibrin glue in the failure of
      nonoperative management of blunt hepatic trauma.
AB  - BACKGROUND: Most blunt hepatic trauma patients can be managed nonoperatively. The
      current failure rate in adult blunt hepatic trauma is reportedly 0 to 19%. We
      wished to evaluate the applicability of laparoscopy and fibrin glue as a
      minimally invasive alternative to laparotomy in these unsuccessfully nonoperative
      cases. METHODS: All adult patients with blunt hepatic trauma managed
      nonoperatively at Linkou, Chang Gung Memorial Hospital Medical Center, Taipei,
      Taiwan, over a 2-year period from July 1, 1994, to June 30, 1996, were eligible
      for the study. A laparoscopic examination was performed on those who failed
      conservative care before undertaking an exploratory laparotomy. Fibrin glue was
      sprayed over the wound surface if ongoing hemorrhage was evident from any liver
      laceration. The clinical data, operative and laparoscopic findings, operative
      methods, and outcomes of these patients were studied. RESULTS: Of the 61
      patients, 55 patients were successfully treated without operation. Of the six
      failures (10%) all were liver related. After the introduction of laparoscopy, the
      nontherapeutic laparotomy rate would have decreased from 100% (6 of 6) to 50% (3
      of 6), and with the adjunctive use of fibrin glue, the laparotomy rate went down
      to 0% (0 of 6). There were no deaths among the six patients receiving laparoscopy
      and fibrin glues; and only one developed a liver abscess, for a morbidity rate of
      17% (1 of 6). CONCLUSIONS: The selective use of laparoscopy and fibrin glue can
      effectively reduce the nontherapeutic laparotomy rate among blunt hepatic trauma
      patients who fail nonoperative management.

PMID- 9555845
TI  - Relationship between systemic oxygen supply dependency and gastric intramucosal
      PCO2 during progressive hemorrhage.
AB  - BACKGROUND: As systemic oxygen delivery (DO2) is reduced, oxygen consumption
      (VO2) is maintained until a critical level is reached (DO2crit) below which VO2
      becomes supply-dependent and anaerobic metabolism ensues. We examined the
      relationship between gastric intramucosal PCO2 (PiCO2) and the onset of systemic
      supply dependency. We also compared PiCO2 to mixed venous and portal venous blood
      PCO2 (PmvCO2 and PpvCO2) to assess their utility as premonitory indicators of
      supply dependency. METHODS: Six dogs were subjected to stepwise hemorrhage to
      effect a progressive decrease in DO2. Inflection points for changes in VO2,
      PiCO2, PmvCO2, and PpvCO2 versus DO2 were determined. RESULTS: Mean DO2crit was
      6.0 +/- 0.7 mL x kg(-1) x min(-1), whereas the DO2 at which inflection points
      occurred for PiCO2 and PpvCO2 were 13.2 +/- 1.4 and 11.2 +/- 1.5 mL x kg(-1) x
      min(-1), respectively (p < 0.05 for both). CONCLUSION: Continuous monitoring of
      PiCO2 using capnometric recirculating gas tonometry can serve as an early
      indicator of systemic hypoperfusion before the onset of systemic supply
      dependency.

PMID- 9555846
TI  - Resuscitation after uncontrolled venous hemorrhage: Does increased resuscitation
      volume improve regional perfusion?
AB  - BACKGROUND: Recent studies have questioned the use of aggressive fluid
      resuscitation after uncontrolled arterial hemorrhage until the bleeding is
      controlled. However, it remains unknown whether resuscitation after hemorrhage
      from a venous origin (usually nonaccessible to surgical intervention) has any
      beneficial or deleterious effects on regional perfusion. The aim of this study,
      therefore, was to determine whether increased volume of fluid resuscitation after
      uncontrolled venous hemorrhage improves hemodynamic profile and regional
      perfusion in various tissues. MATERIALS AND METHODS: After methoxyflurane
      anesthesia and midline laparotomy, both lumbar veins in the rat were severed,
      which resulted in lowering the mean arterial blood pressure to approximately 40
      mm Hg. This pressure was maintained for 45 minutes by allowing further bleeding
      from the lumbar veins. The abdominal incision was then closed in layers and the
      animals received either 0, 10, or 30 mL of lactated Ringer's solution
      intravenously over a period of 60 minutes. Cardiac output and regional blood flow
      were determined by radioactive microspheres immediately or at 1.5 hours after the
      completion of resuscitation. RESULTS: Fluid resuscitation with 10 or 30 mL
      lactated Ringer's solution increased mean arterial blood pressure and cardiac
      output immediately after resuscitation compared with the nonresuscitated animals.
      At both time points, regional perfusion in the heart, kidney and intestines
      remained significantly decreased compared with the sham values, irrespective of
      the volume of fluid resuscitation. Moreover, no further improvements in
      hemodynamics or regional perfusion occurred when volume resuscitation was
      increased from 10 mL to 30 mL. Total hepatic blood flow, however, increased with
      10 mL lactated Ringer's solution compared with the other hemorrhage groups and
      the increase was evident even at 1.5 hours after resuscitation. CONCLUSIONS:
      Fluid resuscitation after uncontrolled venous bleeding transiently increased
      cardiac output and mean arterial blood pressure compared with nonresuscitated
      animals. Moderate fluid administration, i.e., 10 mL, however, did increase total
      hepatic blood flow. In contrast, increasing the resuscitation volume to 30 mL did
      not improve hemodynamic parameters or regional perfusion. Thus moderate instead
      of no resuscitation or larger volume of resuscitation is recommended in an
      uncontrolled model of venous hemorrhage.

PMID- 9555847
TI  - Neuropsychological symptom presentation after electrical injury.
AB  - OBJECTIVE: This study explored the relationship of neuropsychological complaints
      to accident- and injury-related characteristics, affective state, and work status
      in a group of electrical injury (EI) patients. METHODS: Sixty-three EI patients
      and 22 electricians with no history of electrical shock completed the
      Neuropsychological Symptom Checklist and the Beck Depression Inventory as part of
      an extensive neuropsychological evaluation. RESULTS: The EI group endorsed
      significantly more physical, cognitive, and emotional symptoms than did the
      controls. Symptom complaints were not related to injury parameters or litigation
      status. Only the time interval between injury and assessment accounted for
      differences in symptom presentation, with patients in the postacute stages of
      recovery showing the most cognitive and emotional complaints. CONCLUSION: The
      neuropsychological syndrome of electrical injury survival includes physical,
      cognitive, and emotional complaints. Considering that most electrically injured
      patients are treated within the acute medical setting, greater attention needs to
      be directed early in the course of treatment toward addressing neuropsychologic
      and psychiatric issues.

PMID- 9555848
TI  - Blunt injury of the ascending aorta and aortic arch: repair with hypothermic
      circulatory arrest.

PMID- 9555849
TI  - Successful management of combined penetrating injury of innominate artery and
      trachea.

PMID- 9555850
TI  - Severe brachial plexus injury as a result of snowmobiling: a case series.
AB  - BACKGROUND: Documented snowmobile-related fatalities and injuries have increased;
      however, reports of peripheral nerve injuries are rare. METHODS: This case series
      describes a cluster of severe disabling brachial plexus injuries incurred during
      snowmobiling. Medical record abstraction was used to identify relevant patient
      and event characteristics. RESULTS: All study patients were younger male
      snowmobile drivers. All incidents occurred at speeds in excess of 40 mph. Blood
      alcohol concentrations exceeded legal intoxication limits in most cases. Complete
      damage of the brachial plexus occurred in four of the six patients; severe
      disability occurred in all cases. Five of the six patients sustained associated
      orthopedic shoulder complex injuries. CONCLUSION: This first report of severe
      peripheral nerve damage may signal the advent of more severe nonfatal snowmobile
      related injuries that mimic motorcycle-related injuries, because the maximum
      attainable speeds of snowmobiles have increased. Surveillance of snowmobile
      related injuries is warranted to identify the full spectrum of snowmobile
      injuries and recommend public safety measures.

PMID- 9555851
TI  - Delayed closed reduction of rotatory atlantoaxial dislocation: case report and
      literature review.

PMID- 9555852
TI  - Floating knee with ipsilateral knee dislocation: case report.

PMID- 9555853
TI  - Colonic injury and intraspinal penetration from high-pressure molten plastic
      injection: case report.

PMID- 9555854
TI  - Cytokines and cell adhesion molecules in cerebral ischemia: experimental bases
      and therapeutic perspectives.
AB  - The possibility of reopening an occluded cerebral artery by means of thrombolysis
      has renewed interest in a number of the several mechanisms that are active during
      acute cerebral ischemia. Over recent years, it has become apparent that
      leukocytes play a central role not only during the healing stage of brain
      infarction but also during the early phases of cerebral ischemia, when it is
      postulated that these cells produce harmful effects, particularly in the presence
      of reperfusion. This review is based on the critical analysis of more than 150
      publications dealing with the role of leukocytes and some inflammatory mediators
      (cytokines, chemokines, and adhesion molecules) in cerebral ischemia. Animal
      studies indicate that leukocyte involvement is promoted by a variety of
      inflammatory molecules produced immediately after the onset of cerebral ischemia.
      Considerable experimental evidence suggests that these mediators play a key role
      in the progression from ischemia to irreversible injury (ie, cellular death and
      necrosis). However, the precise role of each molecule alone remains to be further
      elucidated as well as in relation to the complex network existing among different
      mediators. Progress in our understanding of the inflammatory mechanisms operating
      in cerebral ischemia has enabled the testing of new compounds with promising
      results in animals; in contrast, one recent controlled trial of an anti-leukocyte
      molecule in acute stroke patients showed negative results. This discrepancy may
      derive in part from our incomplete understanding of the complexity of the
      inflammatory mechanisms involved in cerebral ischemia. Our analysis suggests that
      until sufficient knowledge of the underlying disease mechanisms is acquired, more
      care should be taken when testing new and potentially efficacious drugs in stroke
      patients.

PMID- 9555855
TI  - Sol Sherry lecture in thrombosis: how thrombin 'talks' to cells: molecular
      mechanisms and roles in vivo.

PMID- 9555856
TI  - Ultrastructural localization of secretory type II phospholipase A2 in
      atherosclerotic and nonatherosclerotic regions of human arteries.
AB  - We recently reported on the immunolocalization of type II secretory nonpancreatic
      phospholipase A2 (snpPLA2) in human atherosclerotic lesions. In the present
      study, we present data on the distribution and ultrastructural localization of
      snpPLA2 in adjacent nonatherosclerotic and atherosclerotic regions of human
      arteries. Electron microscopy (EM) of immunogold labeling techniques with a
      monoclonal antibody was used to analyze arterial tissue. The human specimens
      analyzed were obtained from autopsy and surgery cases. The results with EM showed
      a stronger snpPLA2 immunoreactivity in regions of arteries with atherosclerotic
      lesions than in regions without lesions from the same individual. snpPLA2
      immunoreactivity was stronger in the arterial intima of atherosclerotic than of
      nonatherosclerotic tissue. EM-immunogold examination revealed that the majority
      of snpPLA2 was localized along the extracellular matrix, associated with collagen
      fibers and other extracellular matrix structures. Intracellular snpPLA2 was
      observed in electron-dense vesicles in intimal cells. snpPLA2 was also found in
      contact with large, extracellular lipid droplets. These results support the
      hypothesis that extracellular snpPLA2 is localized at sites where it may
      hydrolyze phospholipids from lipoproteins and lipid aggregates retained in the
      extracellular matrix of the arterial wall. This may be a mechanism for in situ
      release of proinflammatory lipids, free fatty acids, and lysophosphatidylcholine
      in regions of apolipoprotein B accumulation, which are abundant in
      atherosclerotic lesions.

PMID- 9555857
TI  - Lipoprotein lipase gene variation is associated with a paternal history of
      premature coronary artery disease and fasting and postprandial plasma
      triglycerides: the European Atherosclerosis Research Study (EARS).
AB  - The H-allele of the intron 8 HindIII polymorphism in the lipoprotein lipase (LPL)
      gene has been associated with a lower risk of myocardial infarction (MI) and
      plasma levels of triglycerides (TG). To test whether the HindIII site was in
      linkage disequilibrium with the functional variant LPL Serine447Stop (S447X),
      subjects from the European Atherosclerosis Research Study (EARS I) were genotyped
      for both polymorphic sites. This study included 515 offspring of fathers with a
      premature (<55 years old) MI, who were designated cases, and 930 age- and sex
      matched control subjects from five different regions of Europe. Linkage
      disequilibrium between the two sites was very strong (>.99), with only three of
      the four possible haplotypes identified: H+S447, H-S447, and H-X447. The
      frequency of the H-X447 but not of the H-S447 haplotype was significantly lower
      in cases than in control subjects (.090 versus .117, P<.01) suggesting a
      protective effect for MI, with this difference being consistent in all five
      regions of Europe. Compared with individuals homozygous for the H+S447 haplotype,
      the odds ratio of having a paternal history of premature MI for H-X447
      heterozygotes (approximately 20% of the population) was 0.71 (95% confidence
      interval, 0.55 to 0.92). In addition, there was an increase of the H-X447
      haplotype frequency from north to south in control subjects (0.119 in Finland to
      0.143 in the Mediterranean region, P<.01). Compared with the H+S447 haplotype,
      the H-X447 haplotype was associated with significantly lower concentrations of
      plasma TGs (5.4% lower, P=.01), with this effect being consistent over the
      regions of Europe. There was no significant evidence for a heterogeneity of
      effect between males and females or between cases and control subjects, although
      the effect on TG levels appeared to be the greatest in male cases (11% lower,
      P=.05). In a second study (EARS II), of 332 cases and 342 control subjects,
      postprandial clearance of TGs after a standard fat meal was examined. The H-X447
      haplotype was associated with significantly lower postprandial triglyceride
      levels than was the H+S447 haplotype (9.4% smaller area under the curve, P<.05).
      Thus, the effects on MI risk and plasma lipids associated with the H allele
      appeared to be mainly mediated by the X447 mutation, and although the lowering
      effects associated with the H-X447 haplotype on fasting and postprandial TGs are
      not large, they are consistent with the lowering effect observed on MI risk
      throughout Europe.

PMID- 9555858
TI  - Influence of biochemical alterations on arterial stiffness in patients with end
      stage renal disease.
AB  - The incremental elastic modulus of the common carotid and radial arteries is
      increased in patients with end-stage renal disease (ESRD), independently of blood
      pressure, wall stress, and the presence of atherosclerotic alterations. Whether
      biochemical factors may be involved in the arterial changes and related to renal
      dysfunction remain largely ignored. To assess this question, we measured aortic
      (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial)
      pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in
      comparison with 57 control subjects similar in age, sex ratio, and mean blood
      pressure. We evaluated arterial blood pressure by sphygmomanometry, aortic
      calcifications and cardiac mass by echography, and routine biochemical
      parameters, total plasma homocysteine, and plasma endothelin levels by standard
      techniques. In the population of patients with ESRD, on the basis of multiple
      stepwise regression analysis, aortic PWV was positively and independently
      correlated with systolic blood pressure (P<.0001), age (P<.0001), prevalence of
      aortic calcification (P=.0004), and the prevalence of diabetes mellitus
      (P=.0043). Upper-limb PWV was influenced exclusively by mean blood pressure
      (P<.0001). Lower-limb PWV was positively and independently correlated with plasma
      total homocysteine (P=.0004) and plasma endothelin (P=.0187) only. At any
      vascular site, PWV was not independently correlated with tobacco consumption;
      plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass
      index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was
      independently correlated with cardiac mass (P=.0022). This study provides
      evidence that in ESRD patients, the stiffness of the arterial wall and cardiac
      mass are strongly influenced by biochemical factors related to the kidney
      alterations and are independent of age and blood pressure level. Increased plasma
      endothelin and homocysteine may be specifically involved in the vascular damage
      of lower limbs.

PMID- 9555859
TI  - Role of macrophage glycosaminoglycans in the cellular catabolism of oxidized LDL
      by macrophages.
AB  - Macrophage binding sites for oxidized LDL (Ox-LDL) include class A scavenger
      receptors (SR-As), the CD-36 molecule, and an additional but hitherto
      unidentified binding site. Because cell-surface glycosaminoglycans (GAGs) were
      previously shown to be involved in the cellular uptake of native LDL and
      lipoprotein(a), several strategies to assess the participation of heparan sulfate
      (HS) and chondroitin sulfate (CS) in macrophage catabolism of Ox-LDL were used.
      First, incubation of J-774 A.1 macrophage-like cells with either heparinase or
      chondroitinase, or with both enzymes together, reduced the binding, uptake, and
      degradation of 125I-Ox-LDL by 20% to 45%, in comparison with control nontreated
      cells, while catabolism of 125I-labeled acetylated LDL (Ac-LDL) and native LDL
      were unaffected. Second, the proteoglycan (PG) cellular content was increased by
      cell enrichment with exogenous GAGs or by using human monocyte-derived
      macrophages from two patients with Sanfilippo mucopolysaccharidosis, which are
      characterized by cellular HS accumulation. In these macrophages, cellular uptake
      of 125I-Ox-LDL increased, while catabolism of 125I-Ac-LDL and native LDL were
      unaffected. Experiments using conditioned media from control, heparinase
      digested, or chondroitinase-digested macrophages indicated that neither secreted
      GAGs nor released digestion products played any role in Ox-LDL catabolism. To
      evaluate potential interactions between cell-surface GAGs and known receptors for
      Ox-LDL, we used excess unlabeled Ac-LDL to block SR-As or anti-CD-36 antibodies
      to block CD-36, and then examined the catabolism of 125I-Ox-LDL by GAG-enriched
      or -depleted macrophages. Both excess unlabeled Ac-LDL and anti-CD-36 antibodies
      reduced 125I-Ox-LDL catabolism, but only excess unlabeled Ac-LDL completely
      abolished the increase in 125I-Ox-LDL catabolism on GAG enrichment of the cells,
      indicating a cooperation between exogenous GAGs and cell-surface SR-As in the
      catabolism of OX-LDL. Moreover, the addition of GAGases to macrophages that were
      preincubated with anti-CD-36 antibodies and excess Ac-LDL further reduced
      macrophage degradation of Ox-LDL in comparison with cells that were pretreated
      only with anti-CD-36 antibodies and Ac-LDL, indicating a more complex role for
      endogenous GAGs. Overall, these studies demonstrate a substantial contribution of
      macrophage-associated GAGs in the catabolism of Ox-LDL, which is mediated in part
      by a cooperation between GAGs and cell-surface SR-As.

PMID- 9555860
TI  - Sterol 27-hydroxylase- and apoAI/phospholipid-mediated efflux of cholesterol from
      cholesterol-laden macrophages: evidence for an inverse relation between the two
      mechanisms.
AB  - Cholesterol-laden, human monocyte-derived macrophages were found to contain 27
      hydroxycholesterol in proportion to their content of cholesterol ester. In
      accordance with previous work with human lung alveolar macrophages, there was a
      significant efflux of 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid
      from the cultured cells. The efflux of 27-hydroxycholesterol was proportional to
      the cellular content of this steroid. Incubation of cholesterol-laden macrophages
      with reconstituted discoidal complexes made from apolipoprotein A-I and
      phospholipids resulted in a decrease in total cellular cholesterol, an increase
      in the efflux of free cholesterol, and a concomitant decrease in the total
      production and efflux of 27-oxygenated steroids, in particular, 3beta-hydroxy-5
      cholestenoic acid. Reconstituted discoidal complexes with the Milano variant of
      apolipoprotein A-I gave virtually identical results, whereas high density
      lipoprotein was less efficient. These results suggest that cultured cholesterol
      laden cells can export some of their excess cholesterol in the form of 27
      hydroxycholesterol, 3beta-hydroxy-5-cholestenoic acid, and free cholesterol. In
      the presence of exogenous cholesterol acceptors, export of free cholesterol
      becomes more effective, resulting in less cholesterol exported via the 27
      hydroxylase pathway. The balance between the two mechanisms for removal of
      cholesterol from macrophages may be of importance for formation of foam cells and
      development of atherosclerosis.

PMID- 9555861
TI  - PAI-1 plasma levels in a general population without clinical evidence of
      atherosclerosis: relation to environmental and genetic determinants.
AB  - Plasminogen activator inhibitor-1 (PAI-1) plasma levels have been consistently
      related to a polymorphism (4G/5G) of the PAI-1 gene. The renin-angiotensin
      pathway plays a role in the regulation of PAI-1 plasma levels. An insertion
      (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has
      been related to plasma and cellular ACE levels. In 1032 employees (446 men and
      586 women; 22 to 66 years old) of a hospital in southern Italy, we investigated
      the association between PAI-1 4G/5G and the ACE I/D gene variants and plasma PAI
      1 antigen levels. None of the individuals enrolled had clinical evidence of
      atherosclerosis. In univariate analysis, PAI-1 levels were significantly higher
      in men (P<.001), alcohol drinkers (P<.001), smokers (P=.009), and homozygotes for
      the PAI-1 gene deletion allele (4G/4G) (P=.012). Multivariate analysis documented
      the independent effect on PAI-1 plasma levels of body mass index (P<.001),
      triglycerides (P<.001), sex (P<.001), PAI-1 4G/5G polymorphism (P=.019), smoking
      habit (P=.041), and ACE I/D genotype (P=.042). Thus, in addition to the markers
      of insulin resistance and smoking habit, gene variants of PAI-1 and ACE account
      for a significant portion of the between-individual variability of circulating
      PAI-1 antigen concentrations in a general population without clinical evidence of
      atherosclerosis.

PMID- 9555862
TI  - Biphasic regulation of transcription factor nuclear factor-kappaB activity in
      human endothelial cells by lysophosphatidylcholine through protein kinase C
      mediated pathway.
AB  - Lysophosphatidylcholine (lysoPC), which is generated in oxidized LDL (Ox-LDL) and
      abundantly exists in atherosclerotic arterial walls, has been shown to alter
      various endothelial functions and induces several endothelial genes expressed in
      atherosclerotic arterial walls. Nuclear factor-kappa B (NF-kappaB), a pleiotropic
      transcription factor, plays an important role in regulation of expression of
      various genes implicated in atherosclerosis. We have previously reported that
      lysoPC transferred from Ox-LDL to endothelial surface membrane activates
      endothelial protein kinase C (PKC), leading to modulated endothelial functions.
      This study was aimed at determining whether lysoPC could modulate activity of
      transcription factors in cultured human umbilical vein endothelial cells (HUVECs)
      by using electrophoretic mobility shift assay. LysoPC was found to increase DNA
      binding activity of NF-kappaB in HUVECs within 15 minutes, which peaked at 1 to 2
      hours and subsequently declined to the baseline level at 6 hours. Lower
      concentrations (5 to 15 micromol/L) of lysoPC markedly increased NF-kappaB
      activity, but higher concentration (50 micromol/L) of lysoPC inhibited the
      activity. Phorbol 12-myristate 13-acetate, a potent activator of PKC, also
      augmented NF-kappaB activity in HUVECs, mimicking the effects of lysoPC;
      furthermore, calphostin C and chelerythrine chloride, specific PKC inhibitors,
      and alpha-tocopherol, a clinically potent PKC inhibitor, suppressed the lysoPC
      induced NF-kappaB activation. These results indicate that lysoPC regulates NF
      kappaB activity in a biphasic manner dependent on its concentrations and
      incubation time in human endothelial cells and the endothelial PKC activation may
      in part be involved in the lysoPC-induced NF-kappaB activation. Thus, the time
      course and the positive and negative biphasic regulatory actions of lysoPC on NF
      kappaB activity in endothelial cells might exhibit a unique effect of lysoPC in
      arterial walls on the different stages of atherosclerosis.

PMID- 9555863
TI  - IDL composition and angiographically determined progression of atherosclerotic
      lesions during simvastatin therapy.
AB  - Some patients with coronary artery disease experience continued progression of
      one or more coronary lesions despite treatment with drugs that inhibit 3-hydroxy
      3-methylglutaryl coenzyme A reductase activity and markedly lower plasma
      cholesterol levels. We examined relationships between the progression of coronary
      artery lesions and plasma lipoproteins, in particular intermediate density
      lipoprotein (IDL) and its composition, in 38 patients with coronary artery
      disease who had been treated with simvastatin for 2 years. Patients were given
      lipid-lowering dietary advice; 3 months later they were started on simvastatin
      therapy (10 mg/d) for 1 month, and after review of their plasma cholesterol
      levels, the dose was increased to 20 mg/d and later to 40 mg/d if the target
      level of plasma cholesterol had not been attained. Progression of lesions was
      determined by serial quantitative coronary angiography (variability of 5.5%) and
      was defined as an increase in percent diameter stenosis (%S)> or =10%; regression
      was defined as a decrease in %S > or =10%. The proportions of cholesteryl esters
      (CEs) and free cholesterol decreased significantly (P<.001), and proportions of
      protein and triglycerides increased significantly (P<.001) in IDL during
      simvastatin therapy. The CE content of IDL decreased significantly (-7.2 weight
      [wt]%, n=20, P<.001) in nonprogressors (patients who did not show progression of
      any lesions) and did not change significantly (-1.8 wt%, n=14, P=.36) in
      progressors (patients who showed progression of one or more lesions without
      regression of any lesion). This decrease in IDL CE content in nonprogressors was
      significantly (P=.01) different compared with the corresponding change in
      patients classified as progressors. Mean plasma cholesterol concentration tended
      to increase in progressors (0.47 mmol/L) and tended to decrease in nonprogressors
      (-0.39 mmol/L) during the initial 3-month diet period, and these changes were
      significantly different (P=.02). Furthermore, this change in plasma cholesterol
      level during the initial diet period was correlated significantly with the change
      in IDL CE content during the entire study (r=.348, n=38, P=.03). These data
      suggest that IDL CE content may be a determinant of progression of coronary
      lesions and may be influenced by compliance with or metabolic response to lipid
      lowering dietary advice in patients with coronary artery disease during
      simvastatin treatment.

PMID- 9555864
TI  - Sex and topographic differences in associations between large-artery wall
      thickness and coronary risk profile in a French working cohort: the AXA Study.
AB  - Previous reports have investigated associations between carotid intima-media
      thickness (IMT) and cardiovascular risk factors. Our objective was to investigate
      this question in greater depth by measuring both femoral and carotid IMT in
      relation to sex and multifactorial coronary risk. We investigated carotid and
      femoral artery IMT by using ultrasonography in 326 men and 462 women, 17 to 65
      years old. We also evaluated body mass index, blood pressure, blood lipids,
      glucose, smoking, and Framingham coronary risk. In both vessels, IMT was lower in
      women than in men. Significant relations between carotid and femoral IMT existed
      with age and most risk factors in both sexes. After adjustment for age, carotid
      IMT was related to risk factors in both sexes except for diastolic blood
      pressure, HDL cholesterol, and smoking in women, whereas femoral IMT was related
      to triglycerides and smoking in both sexes, systolic blood pressure and blood
      glucose in men, and total and HDL cholesterol in women. Significant unadjusted
      and age-adjusted relations of Framingham risk existed with carotid and femoral
      IMT in both sexes, but slopes of these relations were greater (1) before than
      after age adjustment, (2) in men than in women at both sites, except the femoral
      artery after age adjustment, and (3) at the carotid than at the femoral site in
      both sexes before age adjustment. Carotid IMT in men appears to be a more
      powerful predictor than it is in women and femoral IMT in both sexes in
      reflecting multifactorial coronary risk burden, but these differences are partly
      conditional on age.

PMID- 9555865
TI  - Molecular genetic study of Finns with hypoalphalipoproteinemia and
      hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of
      lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very
      low serum HDL cholesterol levels.
AB  - In an attempt to identify genetic factors underlying extreme alterations of serum
      HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C
      levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men,
      one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to
      3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some
      other mutations proposed to affect HDL-C levels. One of the probands had corneal
      opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B
      concentration; the other had anemia and presented with stomatocytosis in his
      peripheral blood. The first proband was found to be homozygous for a novel LCAT
      Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys
      mutation we described previously. Transient expression of the mutant LCAT(Fin)
      cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low
      HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT
      Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase
      (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group
      (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier
      of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in
      the high-HDL-C group and subsequently demonstrated cosegregation of the mutant
      allele with elevated HDL-C levels in the proband's family. In conclusion, we have
      identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with
      the LPL Asn291Ser mutation, represents a relatively common genetic cause of
      diminishing HDL-C levels, at least among Finns. This article also reports
      occurrence of a CETP mutation in subjects having non-Japanese roots.

PMID- 9555866
TI  - Factor VIIa response to a fat-rich meal does not depend on fatty acid
      composition: a randomized controlled trial.
AB  - A fat-rich meal increases activated factor VII (FVIIa), but it is not clear
      whether this increase depends on the fatty acid composition of the meal.
      Therefore, we studied the FVIIa response to fat-rich meals with different fatty
      acid composition in a randomized controlled crossover trial and investigated
      whether this response is mediated by an increase in serum triglycerides. Elderly
      women (> 60 years, n=91) received on separate days four different fat-rich
      breakfasts (50 energy percent [en%] of fat) and a control breakfast (1.5 en% fat;
      crossover). The fat-rich breakfasts differed in fatty acid composition: one rich
      in palmitic acid (21.7 g), one in stearic acid (18.6 g), and the other two in
      linoleic and linolenic acid-one with a ratio 3:1 (12.5/3.9 g) and the other with
      a ratio of 15:1 (18.8/1.2 g). At 8 AM before the breakfast (fasting) and at 1 and
      3 PM, blood samples were taken, in which FVIIa and serum triglycerides were
      measured. FVIIa response to the fat-rich meals ranged from 11.6 mU/mL (95%
      confidence interval: 8.3,14.9) on the stearic meal to 15.9 mU/mL (12.0,19.8) on
      the linoleic/linolenic 15:1 meal at 1 PM and from 14.9 mU/mL (10.6,19.2) to 21.1
      mU/mL (16.6,25.6) for the same meals at 3 PM. The responses did not differ
      between the fat-rich meals. After the control breakfast, FVIIa decreased, with
      6.3 mU/mL (3.9,8.7) at 1 PM and 8.7 mU/mL (6.3,11.1) at 3 PM. The triglyceride
      response was lower after both linoleic/linolenic rich breakfasts compared with
      the palmitic and stearic breakfast (P<.05) and was not associated with the FVIIa
      response at any of the blood sampling occasions. The results of this study show
      that the response of FVIIa to a fat-rich meal is independent of its fatty acid
      composition and is not mediated by serum triglycerides.

PMID- 9555867
TI  - Genetic analysis of the difference in diet-induced atherosclerosis between the
      inbred mouse strains SM/J and NZB/BINJ.
AB  - To identify the genetic factors affecting susceptibility to atherosclerosis, we
      studied the inheritance of plasma total cholesterol (TC) and HDL cholesterol (HDL
      C) concentrations and susceptibility to atherosclerotic lesion formation in an
      (SM/J[SM] x NZB/B1NJ[NZB]) outcross, an (SM/NZB)FI[F1] x SM backcross, and the
      NXSM recombinant inbred (RI) strain set. After 18 or 26 weeks on the atherogenic
      diet, lesion sizes in female mice were 160+/-110 (SE) microm2 for NZB, 100+/-60
      for F1, and 3800+/-920 for SM. After 0, 4, or 26 weeks on the atherogenic diet,
      NZB had higher TC and HDL-C levels than either SM or F1. The F1 progeny had TC
      and HDL-C levels slightly higher than or similar to the SM/J parent, while lesion
      size in the F1 progeny was more similar to the NZB parent. Among the 15 RI
      strains, 8 resembled NZB and F1, 3 resembled SM, and 4 were intermediate between
      NZB and SM for lesion size. For the (SM x NZB)F1 x SM backcross offspring, 26
      resembled NZB and F1, 7 resembled SM, and 6 were intermediate between NZB and SM
      for lesion size. There was poor correlation between lesion size and plasma TC or
      HDL-C in the parental strains and the backcross. These data suggest that
      resistance to atherosclerosis is determined by at least one major dominant gene
      contributed by the NZB strain, which we have named Ath8. Ath8 segregates
      independently of genes controlling TC and HDL-C levels.

PMID- 9555868
TI  - Elevated plasma fibrinogen: cause or consequence of cardiovascular disease?
AB  - An association between increased plasma fibrinogen and an increased risk for
      myocardial infarction (MI) is well established, but the nature of this
      association is subject to debate. Our aim was to shed light on the potentially
      causal nature of this association. We examined whether increased plasma
      fibrinogen, due to a condition that is independent of cardiovascular events, also
      increases the risk for MI. A case-control study was performed in 139 subjects
      with a history of MI and 287 control subjects selected from the Rotterdam Study,
      a population-based cohort of 7983 subjects aged 55 years and older. The genotype
      of the -455G/A polymorphism in the fibrinogen beta-gene was determined by
      polymerase chain reaction. Functional plasma fibrinogen levels were determined
      according to von Clauss. The plasma level of fibrinogen was significantly higher
      in subjects with one or two A alleles compared with subjects with the GG
      genotype: 3.8 (95% confidence interval [CI], 3.6 to 3.9) g/L and 3.6 (3.5 to 3.7)
      g/L, respectively. With increasing plasma fibrinogen level, the risk for MI
      increased gradually; a rise in fibrinogen of 1 g/L was associated with a 45%
      increased risk (odds ratio adjusted for age, sex, and smoking, 1.45; 95% CI, 1.12
      to 1.88). There was no association between the genotype of the -455G/A
      polymorphism and the risk for MI. The -455G/A polymorphism is therefore
      associated with increased plasma fibrinogen levels but not with an increased risk
      for MI. These findings indicate that an increased plasma fibrinogen level due to
      this genetic factor does not increase the risk for MI.

PMID- 9555869
TI  - Lysophosphatidylcholine is involved in the antigenicity of oxidized LDL.
AB  - Lysophosphatidylcholine (LPC) is formed by hydrolysis of PC in low density
      lipoprotein (LDL) and cell membranes by phospholipase A2 or by oxidation.
      Oxidized (ox) LDL activates endothelial cells, an effect mimicked by LPC. oxLDL
      also has the capacity to activate T and B cells, and antibody titers to oxLDL are
      related to the degree of atherosclerosis. The antigen in oxLDL responsible for
      its immune-stimulatory capacity is not well characterized, and we hypothesized
      that LPC was involved. We demonstrate herein the presence of antibodies against
      LPC, both of the IgG and IgM isotype, in 210 healthy individuals. This antibody
      reactivity was not specifically related to oxidation of the fatty acid moiety in
      LPC, since LPC containing only palmitic acid showed antibody titers equivalent to
      those of LPC containing unsaturated fatty acids. Antibody titers to PC were low
      compared with LPC, and hydrolysis of PC at the sn-2 position is thus essential
      for immune reactivity. There was a close correlation between anti-oxLDL and anti
      LPC antibodies. Furthermore, LPC competitively inhibited anti-oxLDL reactivity,
      which indicates that LPC may explain a significant part of the immune-stimulatory
      properties of oxLDL. LPC, being a lipid, is not likely to be an antigen itself.
      Instead, LPC could form immunogenic complexes with peptides, which may induce and
      potentiate immune reactions in the vessel wall. This study adds to the evidence
      that LPC is an important component of oxLDL and emphasizes the potential role of
      phospholipase A2 in atherosclerosis.

PMID- 9555870
TI  - Macrophage phenotype in mice deficient in both macrophage-colony-stimulating
      factor (op) and apolipoprotein E.
AB  - Mice deficient in both macrophage-colony-stimulating factor (M-CSF, op) and
      apolipoprotein E (apoE) have elevated cholesterol levels but are protected from
      atherosclerosis. To assess the contribution of macrophage (Mphi) phenotypic
      heterogeneity and scavenger receptor (SR-A) expression to this seeming paradox,
      we characterized the Mphi phenotype by immunohistochemistry in these animals.
      Lesion size was determined in animals fed a chow or Western-type diet, and
      lipoprotein clearance studies were performed in vivo. Op0/E0 mice have fourfold
      smaller aortic root lesions than op2/E0 animals despite 2.5-fold higher total
      plasma cholesterol levels. Mphis in atherosclerotic lesions of op2/E0 mice
      constitute a predominantly recruited and M-CSF-dependent population. In addition,
      Mphis in different locations in plaques show phenotypic heterogeneity. SR-A
      expression in op0/E0 mice is reduced in proportion to the decrease in Mphi
      numbers, and M-CSF is thus not an essential requirement for SR-A expression in
      vivo. M-CSF-deficient mice degrade injected AcLDL , showing an adequate level of
      SR-A activity present in vivo. In contrast, beta-VLDL clearance in op0/E0 mice is
      decreased, implicating monocytes/Mphis in its catabolism. There is prominent
      lipid accumulation in op2/E0 Kupffer cells and hepatocytes but not in M-CSF
      independent Kupffer Mphis from op0/E0 mice. SR-A, while abundantly expressed on
      both Kupffer cells and sinusoidal endothelial cells in op2/E0 mice, remains
      mainly on sinusoidal endothelial cells in op0/E0 mice. This may explain
      preservation of SR-A activity in these animals. Our findings clearly illustrate
      the importance of both M-CSF and M-CSF-dependent monocytes/Mphis in maintaining
      cholesterol homeostasis and in atherogenesis.

PMID- 9555871
TI  - Increased degradation of lipoprotein(a) in atherosclerotic compared with
      nonlesioned aortic intima-inner media of rabbits: in vivo evidence that
      lipoprotein(a) may contribute to foam cell formation.
AB  - To investigate a potential role of lipoprotein(a) [Lp(a)] in foam cell formation,
      we have measured the degradation rates of Lp(a) and LDL in the rabbit aorta in
      vivo. Lp(a) (or LDL) was labeled with both 113I-TC and 125I and injected into 17
      rabbits with extensive aortic atherosclerosis and into 16 rabbits without
      atherosclerosis. As the protein moiety of the doubly labeled lipoproteins is
      degraded, 131I-TC is trapped in the cell, whereas 125I diffuses out of the cell.
      Twenty-four hours after injection, 12 samples of the aorta and biopsies from 9
      other tissues were removed. The degradation rate of Lp(a) (percent of plasma pool
      per gram tissue per day) was less than that of LDL in the adrenals and in the
      intestine. In contrast, degradation rates of Lp(a) and LDL were similar in liver,
      spleen, kidney, heart, lung, skeletal muscle, and adipose tissue. In nonlesioned
      aortic intima-inner media, the degradation rate of Lp(a) was 39% of that of LDL
      (t test: P <.05 in aortic arch and thoracic aorta), whereas the degradation rates
      of Lp(a) and LDL were similar in atherosclerotic aortic intima-inner media. Lp(a)
      degradation rates were markedly increased in atherosclerotic compared with
      nonlesioned aortic intima-inner media: 28.2+/-9.2 x 10(-7)% and 5.0+/-0.6 x 10(
      7)% of the plasma pool per gram tissue per day in the intima-inner media of the
      proximal segment of atherosclerotic and nonlesioned aorta, respectively (t test:
      P <.01). These results suggest that the metabolism of Lp(a) is different from
      that of LDL in nonlesioned arterial intima, possibly reflecting that Lp(a) is
      degraded by LDL receptors in arterial intima less efficiently than LDL. The
      results also indicate that the degradation rate of Lp(a) is markedly increased in
      atherosclerotic lesions of rabbits, supporting the idea that Lp(a) contributes to
      foam cell formation during the development of atherosclerosis.

PMID- 9555872
TI  - Alcohol withdrawal-induced change in lipoprotein(a): association with the growth
      hormone/insulin-like growth factor-I (IGF-I)/IGF-binding protein-1 (IGFBP-1)
      axis.
AB  - Lipoprotein(a) [Lp(a)] is an important risk factor for cardiovascular disease.
      Alcohol is one of the few nongenetic factors that lower Lp(a) levels, but the
      metabolic mechanisms of this action are unknown. Alcohol inhibits the growth
      hormone (GH)/insulin-like growth factor-I (IGF-I) axis. Alcohol might also affect
      IGF-binding protein-1 (IGFBP-1), which is an acute inhibitor of IGF-I. We studied
      how alcohol withdrawal affects Lp(a) levels and the GH/IGF-I/IGFBP-1 axis. Male
      alcohol abusers (n=27; 20 to 64 years old) were monitored immediately after
      alcohol withdrawal for 4 days. Twenty-six healthy men, mainly moderate drinkers,
      served as control subjects. Fasting blood samples were drawn to determine Lp(a),
      IGF-I, and IGFBP-1 (by ELISA, RIA, and immunoenzymometric assay, respectively).
      Nocturnal (12 hours) urine collection was performed in 9 alcoholics and 11
      control subjects for GH analyses (RIA). The groups were similar in age and body
      mass index. Lp(a), GH, and IGF-I tended to be lower and IGFBP-1 higher in the
      alcoholics immediately after alcohol withdrawal than in the control subjects.
      During the 4-day observation in alcoholics, Lp(a) levels increased by 64% and IGF
      I levels by 41%, whereas IGFBP-1 levels decreased by 59% (P<.001 after ANOVA for
      all comparisons). Urinary GH levels tended to decline. The increase in Lp(a)
      correlated inversely with the changes in IGFBP-1 (r= -.63, P<.001, n=27) and GH
      (r=-.70, P<.05, n=9), but not with IGF-I. In multiple regression analysis, the
      main predictors for the increase in Lp(a) were IGFBP-1 and urinary GH. In
      conclusion, alcohol withdrawal induces interrelated and potentially atherogenic
      changes in Lp(a) and IGFBP-1 levels.

PMID- 9555873
TI  - Familial HDL deficiency characterized by hypercatabolism of mature apoA-I but not
      proapoA-I.
AB  - We have previously described patients with familial high density lipoprotein
      (HDL) deficiency (FHD) having a marked reduction in the plasma concentration of
      HDL cholesterol and apolipoprotein (apo) A-I but lacking clinical manifestations
      of Tangier disease or evidence of other known causes of HDL deficiency. To
      determine whether FHD in these individuals was associated with impaired HDL
      production or increased HDL catabolism, we investigated the kinetics of plasma
      apoA-I and apoA-II in two related FHD patients (plasma apoA-I, 17 and 37 mg/dL)
      and four control subjects (apoA-I, 126+/-18 mg/dL, mean+/-SD) by using a primed
      constant infusion of deuterated leucine. Kinetic analysis of plasma
      apolipoprotein enrichment curves demonstrated that mature plasma apoA-I
      production rates (PRs) were similar in patients and control subjects (7.9 and 9.1
      versus 10.5+/-1.7 mg x kg[-1] x d[-1]). Residence times (RTs) of mature apoA-I
      were, however, significantly less in FHD patients (0.79 and 1.66 days) compared
      with controls (5.32+/-1.05 days). Essentially normal levels of plasma proapoA-I
      (the precursor protein of apoA-I) in FHD patients were associated with normal
      plasma proapoA-I PRs (7.8 and 10.4 versus 10.9+/-2.6 mg x kg[-1] x d[-1]) and
      proapoA-I RTs (0.18 and 0.15 versus 0.16+/-0.03 day). The RTs of apoA-II were,
      however, less in patients (3.17 and 2.92 days) than control subjects (7.24+/-0.71
      days), whereas the PRs of apoA-II were similar (1.8 and 1.9 versus 1.7+/-0.2 mg x
      kg[-1] x d[-1]). Increased plasma catabolism of apoA-II in FHD patients was
      associated with the presence in plasma of abnormal apoA-II-HDL (without apoA-I).
      These results demonstrate that FHD in our patients is characterized, like Tangier
      disease, by hypercatabolism of mature apoA-I and apoA-II, but unlike Tangier
      disease, by essentially normal plasma catabolism and concentration of proapoA-I.

PMID- 9555874
TI  - Distribution and synthesis of apolipoprotein J in the atherosclerotic aorta.
AB  - The distribution of apolipoprotein (apo) J during the development of
      atherosclerosis in the human aorta was evaluated by immununohistochemical
      observation, together with the other apolipoprotein A-I, A-II, B, C-III, and E.
      Although apoJ was never observed in the normal aorta (ie, without any intimal
      lesions or intimal thickening), it was distributed not only in the intima but
      also in the media of aortas with diffuse, intimal thickening or atherosclerotic
      lesions. Double immunostaining with antibodies for apoJ and alpha-smooth muscle
      actin revealed apoJ deposition in smooth muscle cells (SMCs) or the aortic stroma
      in the vicinity of SMCs. The extent of apoJ distribution in the aortic wall
      increased with the degree of atherosclerosis development. In addition, the
      distribution pattern of apoJ was very similar to that of apoA-I and E. In situ
      hybridization with human apoJ cDNA demonstrated intense signals in cells
      scattered within the subendothelial space and medial SMCs of the aorta with
      advanced atherosclerosis but not in those of the normal aorta without intimal
      thickening. Furthermore, reverse transcriptase-polymerase chain reaction of the
      cultured human aortic SMCs revealed apoJ mRNA expression in these cells. The
      results indicate that apoJ in the aortic wall originates from not only apoJ
      circulated in the plasma but also apoJ produced by SMCs in the aortic wall.
      Considering the similarities of the distribution between apoJ and apo-A-I or E,
      we hypothesize that apoJ possibly has a protective role against human
      atherosclerosis by its involvement with cholesterol transport from the aortic
      wall to the liver.

PMID- 9555875
TI  - The Working Group report on Science-Based Categories for Abstracts: Submitted to
      the annual scientific sessions. American Heart Association.

PMID- 9555876
TI  - Multiple beta-ketothiolases mediate poly(beta-hydroxyalkanoate) copolymer
      synthesis in Ralstonia eutropha.
AB  - Polyhydroxyalkanoates (PHAs) are a class of carbon and energy storage polymers
      produced by numerous bacteria in response to environmental limitation. The type
      of polymer produced depends on the carbon sources available, the flexibility of
      the organism's intermediary metabolism, and the substrate specificity of the PHA
      biosynthetic enzymes. Ralstonia eutropha produces both the homopolymer poly-beta
      hydroxybutyrate (PHB) and, when provided with the appropriate substrate, the
      copolymer poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) (PHBV). A required
      step in production of the hydroxyvalerate moiety of PHBV is the condensation of
      acetyl coenzyme A (acetyl-CoA) and propionyl-CoA to form beta-ketovaleryl-CoA.
      This activity has generally been attributed to the beta-ketothiolase encoded by
      R. eutropha phbA. However, we have determined that PhbA does not significantly
      contribute to catalyzing this condensation reaction. Here we report the cloning
      and genetic analysis of bktB, which encodes a beta-ketothiolase from R. eutropha
      that is capable of forming beta-ketovaleryl-CoA. Genetic analyses determined that
      BktB is the primary condensation enzyme leading to production of beta
      hydroxyvalerate derived from propionyl-CoA. We also report an additional beta
      ketothiolase, designated BktC, that probably serves as a secondary route toward
      beta-hydroxyvalerate production.

PMID- 9555877
TI  - Enterocins L50A and L50B, two novel bacteriocins from Enterococcus faecium L50,
      are related to staphylococcal hemolysins.
AB  - Enterocin L50 (EntL50), initially referred to as pediocin L50 (L. M. Cintas, J.
      M. Rodriguez, M. F. Fernandez, K. Sletten, I. F. Nes, P. E. Hernandez, and H.
      Holo, Appl. Environ. Microbiol. 61:2643-2648, 1995), is a plasmid-encoded broad
      spectrum bacteriocin produced by Enterococcus faecium L50. It has previously been
      purified from the culture supernatant and partly sequenced by Edman degradation.
      In the present work, the nucleotide sequence of the EntL50 locus was determined,
      and several putative open reading frames (ORFs) were identified. Unexpectedly,
      two ORFs were found to encode EntL50-like peptides. These peptides, termed
      enterocin L50A (EntL50A) and enterocin L50B (EntL50B), have 72% sequence identity
      and consist of 44 and 43 amino acids, respectively. Interestingly, a comparison
      of the deduced sequences of EntL50A and EntL50B with the corresponding sequences
      obtained by Edman degradation shows that these bacteriocins, in contrast to other
      peptide bacteriocins, are secreted without an N-terminal leader sequence or
      signal peptide. Expression in vivo and in vitro transcription/translation
      experiments demonstrated that entL50A and entL50B are the only genes required to
      obtain antimicrobial activity, strongly indicating that their bacteriocin
      products are not posttranslationally modified. Both bacteriocins possess
      antimicrobial activity on their own, with EntL50A being the most active. In
      addition, when the two bacteriocins were combined, a considerable synergism was
      observed, especially with some indicator strains. Even though the enterocins in
      some respects are similar to class II bacteriocins, several conserved features
      common to class II bacteriocins are absent from the EntL50 system. The enterocins
      have more in common with members of a small group of cytolytic peptides secreted
      by certain staphylococci. We therefore propose that the enterocins L50A and L50B
      and the staphylococcal cytolysins together constitute a new family of peptide
      toxins, unrelated to class II bacteriocins, which possess bactericidal and/or
      hemolytic activity.

PMID- 9555878
TI  - Identification of the omega4400 regulatory region, a developmental promoter of
      Myxococcus xanthus.
AB  - Omega4400 is the site of a Tn5 lac insertion in the Myxococcus xanthus genome
      that fuses lacZ expression to a developmentally regulated promoter. Cell-cell
      interactions that occur during development, including C signaling, are required
      for normal expression of Tn5 lac omega4400. The DNA upstream of the omega4400
      insertion has been cloned, the promoter has been localized, and a partial open
      reading frame has been identified. From the deduced amino acid sequence of the
      partial open reading frame, the gene disrupted by Tn5 lac omega4400 may encode a
      protein with an ATP- or GTP-binding site. Expression of the gene begins 6 to 12 h
      after starvation initiates development, as measured by beta-galactosidase
      production in cells containing Tn5 lac omega4400. The putative transcriptional
      start site was mapped, and deletion analysis has shown that DNA downstream of 
      101 bp is sufficient for C-signal-dependent, developmental activation of this
      promoter. A deletion to -76 bp eliminated promoter activity, suggesting the
      involvement of an upstream activator protein. The promoter may be transcribed by
      RNA polymerase containing a novel sigma factor, since a mutation in the M.
      xanthus sigB or sigC gene did not affect Tn5 lac omega4400 expression and the DNA
      sequence upstream of the transcriptional start site did not match the sequence of
      any M. xanthus promoter transcribed by a known form of RNA polymerase. However,
      the omega4400 promoter does contain the sequence 5'-CATCCCT-3' centered at -49
      and the C-signal-dependent omega4403 promoter also contains this sequence at the
      same position. Moreover, the two promoters match at five of six positions in the 
      10 regions, suggesting that these promoters may share one or more transcription
      factors. These results begin to define the cis-acting regulatory elements
      important for cell-cell interaction-dependent gene expression during the
      development of a multicellular prokaryote.

PMID- 9555879
TI  - Divergence of a DNA replication gene cluster in the T4-related bacteriophage
      RB69.
AB  - The genomes of bacteriophages T4 and RB69 are phylogenetically related but
      diverge in nucleotide sequence at many loci and are incompatible with each other
      in vivo. We describe here the biological implications of divergence in a genomic
      segment that encodes four essential DNA replication proteins: gp45 (sliding
      clamp), gp44/62 complex (clamp loader), and gp46 (a recombination protein). We
      have cloned, sequenced, and expressed several overlapping segments of the RB69
      gene 46-45.2-(rpbA)-45-44-62 cluster and compared its features to those of the
      homologous gene cluster from T4. The deduced primary structures of all four RB69
      replication proteins and gp45.2 from this cluster are very similar (80 to 95%
      similarity) to those of their respective T4 homologs. In contrast, the rpbA
      region (which encodes a nonessential protein in T4) is highly diverged
      (approximately 49% similarity) between the two phage genomes and does not encode
      protein in RB69. Expression studies and patterns of high divergence of
      intercistronic nucleotide sequences of this cluster suggest that T4 and RB69
      evolved similar transcriptional and translational control strategies for the
      cistrons contained therein, but with different specificities. In plasmid-phage
      complementation assays, we show that posttranslationally, RB69 and T4 homologs of
      gp45 and the gp44/62 complex can be effectively exchanged between the two phage
      replicase assemblies; however, we also show results which suggest that mixed
      clamp loader complexes consisting of T4 gp62 and RB69 gp44 subunits are not
      active for phage DNA replication. Thus, specificity of the gp44-gp62 interaction
      in the clamp loader marks a point of departure between the T4 and RB69
      replication systems.

PMID- 9555880
TI  - Expression and regulation of the sodF gene encoding iron- and zinc-containing
      superoxide dismutase in Streptomyces coelicolor Muller.
AB  - Streptomyces coelicolor Muller contains two superoxide dismutases (SODs), nickel
      containing (NiSOD) and iron- and zinc-containing SOD (FeZnSOD). The sodF gene
      encoding FeZnSOD was isolated by using PCR primers corresponding to the N
      terminal peptide sequence of the purified FeZnSOD and a C-terminal region
      conserved among known FeSODs and MnSODs. The deduced amino acid sequence
      exhibited highest similarity to Mn- and FeSODs from Propionibacterium shermanii
      and Mycobacterium spp. The transcription start site of the sodF gene was
      determined by primer extension. When the sodF gene was cloned in pIJ702 and
      introduced into Streptomyces lividans TK24, it produced at least 30 times more
      FeZnSOD than the control cells. We disrupted the sodF gene in S. lividans TK24
      and found that the disruptant did not produce any FeZnSOD enzyme activity but
      produced more NiSOD. The expression of the cloned sodF gene in TK24 cells was
      repressed significantly by Ni, consistent with the regulation pattern in
      nonoverproducing cells. This finding suggests that the cloned sodF gene contains
      the cis-acting elements necessary for Ni regulation. When the sodF mRNA in S.
      coelicolor Muller cells was analyzed by S1 mapping of both 5' and 3' ends, we
      found that Ni caused a reduction in the level of monocistronic sodF transcripts.
      Ni did not affect the stability of sodF mRNA, indicating that it regulates
      transcription. S. lividans TK24 cells overproducing FeZnSOD became more resistant
      to oxidants such as menadione and lawsone than the control cells, suggesting the
      protective role of FeZnSOD. However, the sodF disruptant survived as well as the
      wild-type strain in the presence of these oxidants, suggesting the complementing
      role of NiSOD increased in the disruptant.

PMID- 9555881
TI  - Iron uptake in Ustilago maydis: tracking the iron path.
AB  - In this study, we monitored and compared the uptake of iron in the fungus
      Ustilago maydis by using biomimetic siderophore analogs of ferrichrome, the
      fungal native siderophore, and ferrioxamine B (FOB), a xenosiderophore.
      Ferrichrome-iron was taken up at a higher rate than FOB-iron. Unlike ferrichrome
      mediated uptake, FOB-mediated iron transport involved an extracellular reduction
      mechanism. By using fluorescently labeled siderophore analogs, we monitored the
      time course, as well as the localization, of iron uptake processes within the
      fungal cells. A fluorescently labeled ferrichrome analog, B9-lissamine rhodamine
      B, which does not exhibit fluorescence quenching upon iron binding, was used to
      monitor the entry of the compounds into the fungal cells. The fluorescence was
      found intracellularly 4 h after the application and later was found concentrated
      in two to three vesicles within each cell. The fluorescence of the fluorescently
      labeled FOB analog CAT18, which is quenched by iron, was visualized around the
      cell membrane after 4 h of incubation with the ferrated (nonfluorescent)
      compounds. This fluorescence intensity increased with time, demonstrating fungal
      iron uptake from the siderophores, which remained extracellular. We here
      introduce the use of fluorescent biomimetic siderophores as tools to directly
      track and discriminate between different pathways of iron uptake in cells.

PMID- 9555882
TI  - Isolation and characterization of methanophenazine and function of phenazines in
      membrane-bound electron transport of Methanosarcina mazei Go1.
AB  - A hydrophobic, redox-active component with a molecular mass of 538 Da was
      isolated from lyophilized membranes of Methanosarcina mazei Go1 by extraction
      with isooctane. After purification on a high-performance liquid chromatography
      column, the chemical structure was analyzed by mass spectroscopy and nuclear
      magnetic resonance studies. The component was called methanophenazine and
      represents a 2-hydroxyphenazine derivative which is connected via an ether bridge
      to a polyisoprenoid side chain. Since methanophenazine was almost insoluble in
      aqueous buffers, water-soluble phenazine derivatives were tested for their
      ability to interact with membrane-bound enzymes involved in electron transport
      and energy conservation. The purified F42OH2 dehydrogenase from M. mazei Go1
      showed highest activity with 2-hydroxyphenazine and 2-bromophenazine as electron
      acceptors when F420H2 was added. Phenazine-1-carboxylic acid and phenazine proved
      to be less effective. The Km values for 2-hydroxyphenazine and phenazine were 35
      and 250 microM, respectively. 2-Hydroxyphenazine was also reduced by molecular
      hydrogen catalyzed by an F420-nonreactive hydrogenase which is present in washed
      membrane preparations. Furthermore, the membrane-bound heterodisulfide reductase
      was able to use reduced 2-hydroxyphenazine as an electron donor for the reduction
      of CoB-S-S-CoM. Considering all these results, it is reasonable to assume that
      methanophenazine plays an important role in vivo in membrane-bound electron
      transport of M. mazei Go1.

PMID- 9555883
TI  - Suppressor mutation analysis of the sensory rhodopsin I-transducer complex:
      insights into the color-sensing mechanism.
AB  - The molecular complex containing the phototaxis receptor sensory rhodopsin I
      (SRI) and transducer protein HtrI (halobacterial transducer for SRI) mediates
      color-sensitive phototaxis responses in the archaeon Halobacterium salinarum. One
      photon excitation of the complex by orange light elicits attractant responses,
      while two-photon excitation (orange followed by near-UV light) elicits repellent
      responses in swimming cells. Several mutations in SRI and HtrI cause an unusual
      mutant phenotype, called orange-light-inverted signaling, in which the cell
      produces a repellent response to normally attractant light. We applied a
      selection procedure for intragenic and extragenic suppressors of orange-light
      inverted mutants and identified 15 distinct second-site mutations that restore
      the attractant response. Two of the 3 suppressor mutations in SRI are positioned
      at the cytoplasmic ends of helices F and G, and 12 suppressor mutations in HtrI
      cluster at the cytoplasmic end of the second HtrI transmembrane helix (TM2).
      Nearly all suppressors invert the normally repellent response to two-photon
      stimulation to an attractant response when they are expressed with their
      suppressible mutant alleles or in an otherwise wild-type strain. The results lead
      to a model for control of flagellar reversal by the SRI-HtrI complex. The model
      invokes an equilibrium between the A (reversal-inhibiting) and R (reversal
      stimulating) conformers of the signaling complex. Attractant light and repellent
      light shift the equilibrium toward the A and R conformers, respectively, and
      mutations are proposed to cause intrinsic shifts in the equilibrium in the dark
      form of the complex. Differences in the strength of the two-photon signal
      inversion and in the allele specificity of suppression are correlated, and this
      correlation can be explained in terms of different values of the equilibrium
      constant (Keq) for the conformational transition in different mutants and mutant
      suppressor pairs.

PMID- 9555884
TI  - ntn genes determining the early steps in the divergent catabolism of 4
      nitrotoluene and toluene in Pseudomonas sp. strain TW3.
AB  - Pseudomonas sp. strain TW3 is able to oxidatively metabolize 4-nitrotoluene and
      toluene via a route analogous to the upper pathway of the TOL plasmids. We report
      the sequence and organization of five genes, ntnWCMAB*, which are very similar to
      and in the same order as the xyl operon of TOL plasmid pWW0 and present evidence
      that they encode enzymes which are expressed during growth on both 4-nitrotoluene
      and toluene and are responsible for their oxidation to 4-nitrobenzoate and
      benzoate, respectively. These genes encode an alcohol dehydrogenase homolog
      (ntnW), an NAD+-linked benzaldehyde dehydrogenase (ntnC), a two-gene toluene
      monooxygenase (ntnMA), and part of a benzyl alcohol dehydrogenase (ntnB*), which
      have 84 to 99% identity at the nucleotide and amino acid levels with the
      corresponding xylWCMAB genes. The xylB homolog on the TW3 genome (ntnB*) appears
      to be a pseudogene and is interrupted by a piece of DNA which destroys its
      functional open reading frame, implicating an additional and as-yet-unidentified
      benzyl alcohol dehydrogenase gene in this pathway. This conforms with the
      observation that the benzyl alcohol dehydrogenase expressed during growth on 4
      nitrotoluene and toluene differs significantly from the XylB protein, requiring
      assay via dye-linked electron transfer rather than through a nicotinamide
      cofactor. The further catabolism of 4-nitrobenzoate and benzoate diverges in that
      the former enters the hydroxylaminobenzoate pathway as previously reported, while
      the latter is further metabolized via the beta-ketoadipate pathway.

PMID- 9555885
TI  - FtsZ dynamics during the division cycle of live Escherichia coli cells.
AB  - The dynamics and assembly of bacterial cell division protein FtsZ were monitored
      in individual, growing and dividing Escherichia coli cells in real time by
      microculture of a merodiploid strain expressing green fluorescent protein (GFP)
      tagged FtsZ. Cells expressing FtsZ-GFP at levels less than or equivalent to that
      of wild-type FtsZ were able to grow and divide over multiple generations, with
      their FtsZ rings visualized by fluorescence. During the late stages of
      cytokinesis, which constituted the last one-fourth of the cell cycle, the lumen
      of the FtsZ ring disappeared as the whole structure condensed. At this time,
      loops of FtsZ-GFP polymers emanated outward from the condensing ring structure
      and other unstable fluorescent structures elsewhere in the cell were also
      observed. Assembly of FtsZ rings at new division sites occurred within 1 min,
      from what appeared to be single points. Interestingly, this nucleation often took
      place in the predivisional cell at the same time the central FtsZ ring was in its
      final contraction phase. This demonstrates directly that, at least when FtsZ-GFP
      is being expressed, new division sites have the capacity to become fully
      functional for FtsZ targeting and assembly before cell division of the mother
      cell is completed. The results suggest that the timing of FtsZ assembly may be
      normally controlled in part by cellular FtsZ concentration. The use of wide-field
      optical sectioning microscopy to obtain sharp fluorescence images of FtsZ
      structures is also discussed.

PMID- 9555886
TI  - The katX gene, which codes for the catalase in spores of Bacillus subtilis, is a
      forespore-specific gene controlled by sigmaF, and KatX is essential for hydrogen
      peroxide resistance of the germinating spore.
AB  - Previous work has shown that the katX gene encodes the major catalase in dormant
      spores of Bacillus subtilis but that this enzyme has no role in dormant spore
      resistance to hydrogen peroxide. Expression of a katX-lacZ fusion began at
      approximately h 2 of sporulation, and >75% of the katX-driven beta-galactosidase
      was packaged into the mature spore. A mutation in the gene coding for the
      sporulation-specific RNA polymerase sigma factor sigmaF abolished katX-lacZ
      expression, while mutations in genes encoding sigmaE, sigmaG, and sigmaK did not.
      Induction of sigmaF synthesis in vegetative cells also resulted in katX-lacZ
      expression, while induction of sigmaG expression did not; the katX-lacZ fusion
      was also not induced by hydrogen peroxide. Upstream of the in vivo katX
      transcription start site there are sequences with good homology to those upstream
      of known sigmaF-dependent start sites. These data indicate that katX is an
      additional member of the forespore-specific sigmaF regulon. A mutant in the katA
      gene, encoding the major catalase in growing cells, was sensitive to hydrogen
      peroxide during sporulation, while a katX mutant was not. However, outgrowth of
      katX spores, but not katA spores, was sensitive to hydrogen peroxide.
      Consequently, a major function for KatX is to protect germinating spores from
      hydrogen peroxide.

PMID- 9555888
TI  - Identification and characterization of epoxide carboxylase activity in cell
      extracts of Nocardia corallina B276.
AB  - The metabolism of aliphatic epoxides (epoxyalkanes) by the alkene-utilizing
      actinomycete Nocardia corallina B276 was investigated. Suspensions of N.
      corallina cells grown with propylene as the carbon source readily degraded
      propylene and epoxypropane, while suspensions of glucose-grown cells did not. The
      addition of propylene and epoxypropane to glucose-grown cells resulted in a time
      dependent increase in propylene- and epoxypropane-degrading activities that was
      prevented by the addition of rifampin and chloramphenicol. The expression of
      alkene- and epoxide-degrading activities was correlated with the high-level
      expression of several polypeptides not present in extracts of glucose-grown
      cells. Epoxypropane and epoxybutane degradation by propylene-grown cell
      suspensions of N. corallina was stimulated by the addition of CO2 and inhibited
      by the depletion of CO2. Cell extracts catalyzed the carboxylation of
      epoxypropane to form acetoacetate in a reaction that was dependent on the
      addition of CO2, NAD+, and a reductant (NADPH or dithiothreitol). In the absence
      of CO2, epoxypropane was isomerized by cell extracts to form acetone at a rate
      approximately 10-fold lower than the rate of epoxypropane carboxylation.
      Methylepoxypropane was found to be a time-dependent, irreversible inactivator of
      epoxyalkane-degrading activity. These properties demonstrate that epoxyalkane
      metabolism in N. corallina occurs by a carboxylation reaction forming beta-keto
      acids as products and provide evidence for the involvement in this reaction of an
      epoxide carboxylase with properties and cofactor requirements similar to those of
      the four-component epoxide carboxylase enzyme system of the gram-negative
      bacterium Xanthobacter strain Py2 (J. R. Allen and S. A. Ensign, J. Biol. Chem.
      272:32121-32128, 1997). The addition of epoxide carboxylase component I from
      Xanthobacter strain Py2 to methylepoxypropane-inactivated N. corallina extracts
      restored epoxide carboxylase activity, and the addition of epoxide carboxylase
      component II from Xanthobacter Py2 to active N. corallina extracts stimulated
      epoxide isomerase rates to the same levels observed with the purified
      Xanthobacter system. Antibodies raised against Xanthobacter strain Py2 epoxide
      carboxylase component I cross-reacted with a polypeptide in propylene-grown N.
      corallina extracts with the same molecular weight as component I but did not
      cross-react with glucose-grown extracts. Together, these results suggest a common
      pathway of epoxyalkane metabolism for phylogenetically distinct bacteria that
      involves CO2 fixation and the activity of a multicomponent epoxide carboxylase
      enzyme system.

PMID- 9555887
TI  - Use of bacteriophage lambda recombination functions to promote gene replacement
      in Escherichia coli.
AB  - Replacement of Escherichia coli's RecBCD function with phage lambda's Red
      function generates a strain whose chromosome recombines with short linear DNA
      fragments at a greatly elevated rate. The rate is at least 70-fold higher than
      that exhibited by a recBC sbcBC or recD strain. The value of the system is
      highlighted by gene replacement with a PCR-generated DNA fragment. The
      deltarecBCD::Plac-red kan replacement allele can be P1 transduced to other E.
      coli strains, making the hyper-Rec phenotype easily transferable.

PMID- 9555889
TI  - Isolation and characterization of EPD1, an essential gene for pseudohyphal growth
      of a dimorphic yeast, Candida maltosa.
AB  - Additional copies of the centromeric DNA (CEN) region induce pseudohyphal growth
      in a dimorphic yeast, Candida maltosa (T. Nakazawa, T. Motoyama, H. Horiuchi, A.
      Ohta, and M. Takagi, J. Bacteriol. 179:5030-5036, 1997). To understand the
      mechanism of this transition, we screened the gene library of C. maltosa for
      sequences which could suppress this morphological change. As a result, we
      isolated the 5' end of a new gene, EPD1 (for essential for pseudohyphal
      development), and then cloned the entire gene. The predicted amino acid sequence
      of Epdlp was highly homologous to those of Ggp1/Gas1/Cwh52p, a
      glycosylphosphatidylinositol-anchored protein of Saccharomyces cerevisiae, and
      Phr1p and Phr2p of Candida albicans. The expression of EPD1 was moderately
      regulated by environmental pH. A homozygous EPD1 null mutant showed some
      morphological defects and reduction in growth rate and reduced levels of both
      alkali-soluble and alkali-insoluble beta-glucans. Moreover, the mutant could not
      undergo the transition from yeast form to pseudohyphal form induced by additional
      copies of the CEN sequence at pH 4 or by n-hexadecane at pH 4 or pH 7, suggesting
      that EPD1 is not essential for yeast form growth but is essential for transition
      to the pseudohyphal form. Overexpression of the amino-terminal part of Epd1p
      under the control of the GAL promoter suppressed the pseudohyphal development
      induced by additional copies of the CEN sequence, whereas overexpression of the
      full-length EPD1 did not. This result and the initial isolation of the 5' end of
      EPD1 as a suppressor of the pseudohyphal growth induced by the CEN sequence
      suggest that the amino-terminal part of Epd1p may have a dominant-negative effect
      on the functions of Epd1p in the pseudohyphal growth induced by the CEN sequence.

PMID- 9555891
TI  - Generation and properties of a Streptococcus pneumoniae mutant which does not
      require choline or analogs for growth.
AB  - A mutant (JY2190) of Streptococcus pneumoniae Rx1 which had acquired the ability
      to grow in the absence of choline and analogs was isolated. Lipoteichoic acid
      (LTA) and wall teichoic acid (TA) isolated from the mutant were free of
      phosphocholine and other phosphorylated amino alcohols. Both polymers showed an
      unaltered chain structure and, in the case of LTA, an unchanged glycolipid
      anchor. The cell wall composition was also not altered except that, due to the
      lack of phosphocholine, the phosphate content of cell walls was half that of the
      parent strain. Isolated cell walls of the mutant were resistant to hydrolysis by
      pneumococcal autolysin (N-acetylmuramyl-L-alanine amidase) but were cleaved by
      the muramidases CPL and cellosyl. The lack of active autolysin in the mutant
      cells became apparent by impaired cell separation at the end of cell division and
      by resistance against stationary-phase and penicillin-induced lysis. As a result
      of the absence of choline in the LTA, pneumococcal surface protein A (PspA) was
      no longer retained on the cytoplasmic membrane. During growth in the presence of
      choline, which was incorporated as phosphocholine into LTA and TA, the mutant
      cells separated normally, did not release PspA, and became penicillin sensitive.
      However, even under these conditions, they did not lyse in the stationary phase,
      and they showed poor reactivity with antibody to phosphocholine and an increased
      release of C-polysaccharide from the cell. In contrast to ethanolamine-grown
      parent cells (A. Tomasz, Proc. Natl. Acad. Sci. USA 59:86-93, 1968), the choline
      free mutant cells retained the capability to undergo genetic transformation but,
      compared to Rx1, with lower frequency and at an earlier stage of growth. The
      properties of the mutant could be transferred to the parent strain by DNA of the
      mutant.

PMID- 9555890
TI  - The periplasmic, group III catalase of Vibrio fischeri is required for normal
      symbiotic competence and is induced both by oxidative stress and by approach to
      stationary phase.
AB  - The catalase gene, katA, of the sepiolid squid symbiont Vibrio fischeri has been
      cloned and sequenced. The predicted amino acid sequence of KatA has a high degree
      of similarity to the recently defined group III catalases, including those found
      in Haemophilus influenzae, Bacteroides fragilis, and Proteus mirabilis. Upstream
      of the predicted start codon of katA is a sequence that closely matches the
      consensus sequence for promoters regulated in Escherichia coli by the alternative
      sigma factor encoded by rpoS. Further, the level of expression of the cloned katA
      gene in an E. coli rpoS mutant is much lower than in wild-type E. coli. Catalase
      activity is induced three- to fourfold both as growing V. fischeri cells approach
      stationary phase and upon the addition of a small amount of hydrogen peroxide
      during logarithmic growth. The catalase activity was localized in the periplasm
      of wild-type V. fischeri cells, where its role could be to detoxify hydrogen
      peroxide coming from the external environment. No significant catalase activity
      could be detected in a katA null mutant strain, demonstrating that KatA is the
      predominately expressed catalase in V. fischeri and indicating that V. fischeri
      carries only a single catalase gene. The catalase mutant was defective in its
      ability to competitively colonize the light organs of juvenile squids in
      coinoculation experiments with the parent strain, suggesting that the catalase
      enzyme plays an important role in the symbiosis between V. fischeri and its squid
      host.

PMID- 9555892
TI  - IS6110 transposition and evolutionary scenario of the direct repeat locus in a
      group of closely related Mycobacterium tuberculosis strains.
AB  - In recent years, various polymorphic loci and multicopy insertion elements have
      been discovered in the Mycobacterium tuberculosis genome, such as the direct
      repeat (DR) locus, the major polymorphic tandem repeats, the polymorphic GC-rich
      repetitive sequence, IS6110, and IS1081. These, especially IS6110 and the DR
      locus, have been widely used as genetic markers to differentiate M. tuberculosis
      isolates and will continue to be so used, due to the conserved nature of the
      genome of M. tuberculosis. However, little is known about the processes involved
      in generating these or of their relative rates of change. Without an
      understanding of the biological characteristics of these genetic markers, it is
      difficult to use them to their full extent for understanding the population
      genetics and epidemiology of M. tuberculosis. To address these points, we
      identified a cluster of 7 isolates in a collection of 101 clinical isolates and
      investigated them with various polymorphic genetic markers, which indicated that
      they were highly related to each other. This cluster provided a model system for
      the study of IS6110 transposition, evolution at the DR locus, and the effects of
      these on the determination of evolutionary relationships among M. tuberculosis
      strains. Our results suggest that IS6110 restriction fragment length polymorphism
      patterns are useful in grouping closely related isolates together; however, they
      can be misleading if used for making inferences about the evolutionary
      relationships between closely related isolates. DNA sequence analysis of the DR
      loci of these isolates revealed an evolutionary scenario, which, complemented
      with the information from IS6110, allowed a reconstruction of the evolutionary
      steps and relationships among these closely related isolates. Loss of the IS6110
      copy in the DR locus was noted, and the mechanisms of this loss are discussed.

PMID- 9555893
TI  - Lysis genes of the Bacillus subtilis defective prophage PBSX.
AB  - Four genes identified within the late operon of PBSX show characteristics
      expected of a host cell lysis system; they are xepA, encoding an exported
      protein; xhlA, encoding a putative membrane-associated protein; xhlB, encoding a
      putative holin; and xlyA, encoding a putative endolysin. In this work, we have
      assessed the contribution of each gene to host cell lysis by expressing the four
      genes in different combinations under the control of their natural promoter
      located on the chromosome of Bacillus subtilis 168. The results show that xepA is
      unlikely to be involved in host cell lysis. Expression of both xhlA and xhlB is
      necessary to effect host cell lysis of B. subtilis. Expression of xhlB (encoding
      the putative holin) together with xlyA (encoding the endolysin) cannot effect
      cell lysis, indicating that the PBSX lysis system differs from those identified
      in the phages of gram-negative bacteria. Since host cell lysis can be achieved
      when xlyA is inactivated, it is probable that PBSX encodes a second endolysin
      activity which also uses XhlA and XhlB for export from the cell. The chromosome
      based expression system developed in this study to investigate the functions of
      the PBSX lysis genes should be a valuable tool for the analysis of other host
      cell lysis systems and for expression and functional analysis of other lethal
      gene products in gram-positive bacteria.

PMID- 9555894
TI  - Transformation of Rickettsia prowazekii to rifampin resistance.
AB  - Rickettsia prowazekii, the causative agent of epidemic typhus, is an obligate
      intracellular parasitic bacterium that grows directly within the cytoplasm of the
      eucaryotic host cell. The absence of techniques for genetic manipulation hampers
      the study of this organism's unique biology and pathogenic mechanisms. To
      establish the feasibility of genetic manipulation in this organism, we identified
      a specific mutation in the rickettsial rpoB gene that confers resistance to
      rifampin and used it to demonstrate allelic exchange in R. prowazekii. Comparison
      of the rpoB sequences from the rifampin-sensitive (Rifs) Madrid E strain and a
      rifampin-resistant (Rifr) mutant identified a single point mutation that results
      in an arginine-to-lysine change at position 546 of the R. prowazekii RNA
      polymerase beta subunit. A plasmid containing this mutation and two additional
      silent mutations created in codons flanking the Lys-546 codon was introduced into
      the Rifs Madrid E strain of R. prowazekii by electroporation, and in the presence
      of rifampin, resistant rickettsiae were selected. Transformation, via homologous
      recombination, was demonstrated by DNA sequencing of PCR products containing the
      three mutations in the Rifr region of rickettsial rpoB. This is the first
      successful demonstration of genetic transformation of Rickettsia prowazekii and
      represents the initial step in the establishment of a genetic system in this
      obligate intracellular pathogen.

PMID- 9555895
TI  - Visualization of penicillin-binding proteins during sporulation of Streptomyces
      griseus.
AB  - We used fluorescein-tagged beta-lactam antibiotics to visualize penicillin
      binding proteins (PBPs) in sporulating cultures of Streptomyces griseus. Six PBPs
      were identified in membranes prepared from growing and sporulating cultures. The
      binding activity of an 85-kDa PBP increased fourfold by 10 to 12 h of
      sporulation, at which time the sporulation septa were formed. Cefoxitin inhibited
      the interaction of the fluorescein-tagged antibiotics with the 85-kDa PBP and
      also prevented septum formation during sporulation but not during vegetative
      growth. The 85-kDa PBP, which was the predominant PBP in membranes of cells that
      were undergoing septation, preferentially bound fluorescein-6-aminopenicillanic
      acid (Flu-APA). Fluorescence microscopy showed that the sporulation septa were
      specifically labeled by Flu-APA; this interaction was blocked by prior exposure
      of the cells to cefoxitin at a concentration that interfered with septation. We
      hypothesize that the 85-kDa PBP is involved in septum formation during
      sporulation of S. griseus.

PMID- 9555896
TI  - Availability of O2 as a substrate in the cytoplasm of bacteria under aerobic and
      microaerobic conditions.
AB  - The growth rates of Pseudomonas putida KT2442 and mt-2 on benzoate, 4
      hydroxybenzoate, or 4-methylbenzoate showed an exponential decrease with
      decreasing oxygen tensions (partial O2 tension [pO2] values). The oxygen tensions
      resulting in half-maximal growth rates were in the range of 7 to 8 mbar of O2
      (corresponding to 7 to 8 microM O2) (1 bar = 10(5) Pa) for aromatic compounds,
      compared to 1 to 2 mbar for nonaromatic compounds like glucose or succinate. The
      decrease in the growth rates coincided with excretion of catechol or
      protocatechuate, suggesting that the activity of the corresponding oxygenases
      became limiting. The experiments directly establish that under aerobic and
      microaerobic conditions (about 10 mbar of O2), the diffusion of O2 into the
      cytoplasm occurs at high rates sufficient for catabolic processes. This is in
      agreement with calculated O2 diffusion rates. Below 10 mbar of O2, oxygen became
      limiting for the oxygenases, probably due to their high Km values, but the
      diffusion of O2 into the cytoplasm presumably should be sufficiently rapid to
      maintain ambient oxygen concentrations at oxygen tensions as low as 1 mbar of O2.
      The consequences of this finding for the availability of O2 as a substrate or as
      a regulatory signal in the cytoplasm of bacterial cells are discussed.

PMID- 9555897
TI  - PPi-dependent phosphofructokinase from Thermoproteus tenax, an archaeal
      descendant of an ancient line in phosphofructokinase evolution.
AB  - Flux into the glycolytic pathway of most cells is controlled via allosteric
      regulation of the irreversible, committing step catalyzed by ATP-dependent
      phosphofructokinase (PFK) (ATP-PFK; EC 2.7.1.11), the key enzyme of glycolysis.
      In some organisms, the step is catalyzed by PPi-dependent PFK (PPi-PFK; EC
      2.7.1.90), which uses PPi instead of ATP as the phosphoryl donor, conserving ATP
      and rendering the reaction reversible under physiological conditions. We have
      determined the enzymic properties of PPi-PFK from the anaerobic,
      hyperthermophilic archaeon Thermoproteus tenax, purified the enzyme to
      homogeneity, and sequenced the gene. The approximately 100-kDa PPi-PFK from T.
      tenax consists of 37-kDa subunits; is not regulated by classical effectors of ATP
      PFKs such as ATP, ADP, fructose 2,6-bisphosphate, or metabolic intermediates; and
      shares 20 to 50% sequence identity with known PFK enzymes. Phylogenetic analyses
      of biochemically characterized PFKs grouped the enzymes into three monophyletic
      clusters: PFK group I represents only classical ATP-PFKs from Bacteria and
      Eucarya; PFK group II contains only PPi-PFKs from the genus Propionibacterium,
      plants, and amitochondriate protists; whereas group III consists of PFKs with
      either cosubstrate specificity, i.e., the PPi-dependent enzymes from T. tenax and
      Amycolatopsis methanolica and the ATP-PFK from Streptomyces coelicolor.
      Comparative analyses of the pattern of conserved active-site residues strongly
      suggest that the group III PFKs originally bound PPi as a cosubstrate.

PMID- 9555898
TI  - Variation of the ribosomal operon 16S-23S gene spacer region in representatives
      of Salmonella enterica subspecies.
AB  - The 16S-23S spacer regions of two ribosomal operons (rrnA and rrnE) have been
      sequenced in seven representatives of the Salmonella enterica subspecies.
      Isolated nucleotide substitutions were found at the same sites as in Escherichia
      coli but the number of polymorphic sites was much larger, as could be expected
      for a more heterogeneous species. Still, as in E. coli, most of the variation
      found was due to insertions and/or deletions affecting blocks of nucleotides
      generally located at equivalent regions of the putative secondary structure for
      both species. Isolated polymorphic sites generated phylogenetic trees generally
      consistent with the subspecies structure and the accepted relationships among the
      subspecies. However, the sequences of rrnE put subspecies I closer to E. coli K
      12 than to the other S. enterica subspecies. The distribution of polymorphisms
      affecting blocks of nucleotides was much more random, and the presence of
      equivalent sequences in distantly related subspecies, and even in E. coli, could
      reflect relatively frequent horizontal transfer. The smallest 16S-23S spacers in
      other genera of the family Enterobacteriaceae were also sequenced. As expected,
      the level of variation was much larger. Still, the phylogenetic tree inferred is
      consistent with those of 16S rRNA or housekeeping genes.

PMID- 9555899
TI  - An AT-rich tract containing an integration host factor-binding domain and two UP
      like elements enhances transcription from the pilEp1 promoter of Neisseria
      gonorrhoeae.
AB  - The pilE gene of Neisseria gonorrhoeae is transcribed from a sigma70 promoter
      (pilEp1) with an AT-rich tract extending 65 nucleotides upstream of the -35 box.
      Within this region is an integration host factor (IHF)-binding core consensus
      sequence. We have performed a detailed analysis to determine which upstream
      sequences are required for efficient transcription from pilEp1 in N. gonorrhoeae.
      Deletion of sequences upstream of the AT-rich tract had no effect on the level of
      transcription. However, the IHF-binding core consensus sequence and the AT-rich
      sequence further upstream were both required for enhanced levels of transcription
      from this promoter in both N. gonorrhoeae and an Escherichia coli strain
      producing IHF. In addition, an UP-like element positioned between the -35 box and
      the IHF-binding site was required for maximal transcription. The AT-rich region
      upstream of the IHF-binding core consensus sequence can also act as an UP-like
      element when appropriately repositioned upstream of the -35 box.

PMID- 9555900
TI  - Interaction of native and mutant MecI repressors with sequences that regulate
      mecA, the gene encoding penicillin binding protein 2a in methicillin-resistant
      staphylococci.
AB  - Methicillin resistance in staphylococci is mediated by PBP2a, a penicillin
      binding protein with low affinity for beta-lactam antibiotics. The gene encoding
      PBP2a, mecA, is transcriptionally regulated in some clinical isolates by mecR1
      and mecI, genes divergently transcribed from mecA that encode a signal transducer
      and repressor, respectively. The biochemical basis of MecI-mediated mecA
      transcriptional repression was investigated by using purified MecI. In DNase I
      protection studies, MecI protected a 30-bp palindrome encompassing the predicted
      mecA -10 and the mecR1 -35 promoter sequences. The larger palindrome contained 15
      bp of dyad symmetry within which was a smaller 6-bp palindrome. Electrophoretic
      mobility shift assays established a requirement for the entire 15-bp half-site
      for initial repressor binding. Fragments containing the 30-bp palindrome and the
      entire mecA-mecR1 intergenic region were retarded in gels as multiple discrete
      bands varying in molecular size, characteristic of cooperative DNA binding.
      Glutaraldehyde cross-linking confirmed oligomerization of repressor in solution.
      A naturally occurring MecI mutant (MecI*; D39G) repressed mecA transcription
      sixfold less well than the wild type in vivo. Although MecI* protected the same
      target sequences and exhibited similar gel shift patterns to MecI, 5- to 10-fold
      more protein was required. MecI* exhibited defective oligomerization in solution,
      suggesting that the MecI amino terminus is important in protein-protein
      interactions and that protein oligomerization is necessary for optimum
      repression.

PMID- 9555901
TI  - A period-extender gene, pex, that extends the period of the circadian clock in
      the cyanobacterium Synechococcus sp. strain PCC 7942.
AB  - We cloned the pS1K1 plasmid in the process of apparently "complementing" a
      circadian clock mutant of cyanobacterium Synechococcus sp. strain PCC 7942, SP22,
      which has a 22-h period (T. Kondo, N. F. Tsinoremas, S. S. Golden, C. H. Johnson,
      S. Kutsuna, and M. Ishiura, Science 266:1233-1236, 1994). Sequence analysis
      revealed that SP22 did not have a mutation in the genomic DNA segment carried on
      pS1K1, and the sp22 mutation was later found in a recently cloned new clock gene,
      kaiC. Therefore, the period-extender gene pex that was carried on pS1K1 was a
      suppressor gene for the sp22 mutation. The pex gene encoded a protein of 148
      amino acid residues. No meaningful homologs were found in DNA or protein
      databases including the Synechocystis genome database. The pex gene was
      transcribed from 129 and 164 bp upstream of the translation initiation codon as
      0.6-kb transcripts. The Pex protein was detected as a fusion protein with a
      molecular mass of 15 kDa by the epitope tag fusion method using a c-Myc epitope
      tag. Disruption of the pex gene in wild-type cells shortened the period of the
      rhythms by 1 h, although it did not affect other properties of the rhythms,
      whereas its overexpression extended the period by 3 h with a concomitant
      reduction in the amplitude of the rhythms. In various clock mutants examined,
      overexpression caused arrhythmicity. Thus, Pex is likely to function as a
      modifier of the circadian clock in Synechococcus.

PMID- 9555903
TI  - Inorganic polyphosphate in Escherichia coli: the phosphate regulon and the
      stringent response.
AB  - Escherichia coli transiently accumulates large amounts of inorganic polyphosphate
      (polyP), up to 20 mM in phosphate residues (Pi), in media deficient in both Pi
      and amino acids. This transient accumulation is preceded by the appearance of
      nucleotides ppGpp and pppGpp, generated in response to nutritional stresses.
      Mutants which lack PhoB, the response regulator of the phosphate regulon, do not
      accumulate polyP even though they develop wild-type levels of (p)ppGpp when
      subjected to amino acid starvation. When complemented with a phoB-containing
      plasmid, phoB mutants regain the ability to accumulate polyP. PolyP accumulation
      requires high levels of (p)ppGpp independent of whether they are generated by
      RelA (active during the stringent response) or SpoT (expressed during Pi
      starvation). Hence, accumulation of polyP requires a functional phoB gene and
      elevated levels of (p)ppGpp. A rapid assay of polyP depends on its adsorption to
      an anion-exchange disk on which it is hydrolyzed by a yeast exopolyphosphatase.

PMID- 9555902
TI  - A membrane-associated protein, FliX, is required for an early step in Caulobacter
      flagellar assembly.
AB  - The ordered assembly of the Caulobacter crescentus flagellum is accomplished in
      part through the organization of the flagellar structural genes in a regulatory
      hierarchy of four classes. Class II genes are the earliest to be expressed and
      are activated at a specific time in the cell cycle by the CtrA response
      regulator. In order to identify gene products required for early events in
      flagellar assembly, we used the known phenotypes of class II mutants to identify
      new class II flagellar genes. In this report we describe the isolation and
      characterization of a flagellar gene, fliX. A fliX null mutant is nonmotile,
      lacks a flagellum, and exhibits a marked cell division defect. Epistasis
      experiments placed fliX within class II of the flagellar regulatory hierarchy,
      suggesting that FliX functions at an early stage in flagellar assembly. The fliX
      gene encodes a 15-kDa protein with a putative N-terminal signal sequence.
      Expression of fliX is under cell cycle control, with transcription beginning
      relatively early in the cell cycle and peaking in Caulobacter predivisional
      cells. Full expression of fliX was found to be dependent on ctrA, and DNase I
      footprinting analysis demonstrated a direct interaction between CtrA and the fliX
      promoter. The fliX gene is located upstream and is divergently transcribed from
      the class III flagellar gene flgI, which encodes the basal body P-ring monomer.
      Analysis of the fliX-flgI intergenic region revealed an arrangement of cis-acting
      elements similar to that of another set of Caulobacter class II and class III
      flagellar genes, fliL-flgF, that is also divergently transcribed. In parallel
      with the FliL protein, FliX copurifies with the membrane fraction, and although
      its expression is cell cycle controlled, the protein is present throughout the
      cell cycle.

PMID- 9555904
TI  - A Bacillus subtilis gene induced by cold shock encodes a membrane phospholipid
      desaturase.
AB  - Bacillus subtilis grown at 37 degrees C synthesizes saturated fatty acids with
      only traces of unsaturated fatty acids (UFAs). However, when cultures growing at
      37 degrees C are transferred to 20 degrees C, UFA synthesis is induced. We report
      the identification and characterization of the gene encoding the fatty acid
      desaturase of B. subtilis. This gene, called des, was isolated by complementation
      of Escherichia coli strains with mutations in either of two different genes of
      UFA synthesis. The des gene encodes a polypeptide of 352 amino acid residues
      containing the three conserved histidine cluster motifs and two putative membrane
      spanning domains characteristic of the membrane-bound desaturases of plants and
      cyanobacteria. Expression of the des gene in E. coli resulted in desaturation of
      palmitic acid moieties of the membrane phospholipids to give the novel mono-UFA
      cis-5-hexadecenoic acid, indicating that the B. subtilis des gene product is a
      delta5 acyl-lipid desaturase. The des gene was disrupted, and the resulting null
      mutant strains were unable to synthesize UFAs upon a shift to low growth
      temperatures. The des null mutant strain grew as well as its congenic parent at
      20 or 37 degrees C but showed severely reduced survival during stationary phase.
      Analysis of operon fusions in which the des promoter directed the synthesis of a
      lacZ reporter gene showed that des expression is repressed at 37 degrees C, but a
      shift of cultures from 37 to 20 degrees C resulted in a 10- to 15-fold increase
      in transcription. This is the first report of a membrane phospholipid desaturase
      in a nonphotosynthetic organism and the first direct evidence for cold induction
      of a desaturase.

PMID- 9555905
TI  - The Bacillus subtilis DinR binding site: redefinition of the consensus sequence.
AB  - Recently, the DinR protein was established as the cellular repressor of the SOS
      response in the bacterium Bacillus subtilis. It is believed that DinR functions
      as the repressor by binding to a consensus sequence located in the promoter
      region of each SOS gene. The binding site for DinR is believed to be synonymous
      with the formerly identified Cheo box, a region of 12 bp displaying dyad symmetry
      (GAAC-N4-GTTC). Electrophoretic mobility shift assays revealed that highly
      purified DinR does bind to such sites located upstream of the dinA, dinB, dinC,
      and dinR genes. Furthermore, detailed mutational analysis of the B. subtilis recA
      operator indicates that some nucleotides are more important than others for
      maintaining efficient DinR binding. For example, nucleotide substitutions
      immediately 5' and 3' of the Cheo box as well as those in the N4 region appear to
      affect DinR binding. This data, combined with computational analyses of potential
      binding sites in other gram-positive organisms, yields a new consensus (DinR box)
      of 5'-CGAACRNRYGTTYC-3'. DNA footprint analysis of the B. subtilis dinR and recA
      DinR boxes revealed that the DinR box is centrally located within a DNA region of
      31 bp that is protected from hydroxyl radical cleavage in the presence of DinR.
      Furthermore, while DinR is predominantly monomeric in solution, it apparently
      binds to the DinR box in a dimeric state.

PMID- 9555906
TI  - Molecular analysis of the gene encoding F420-dependent glucose-6-phosphate
      dehydrogenase from Mycobacterium smegmatis.
AB  - The gene fgd, which codes for F420-dependent glucose-6-phosphate dehydrogenase
      (FGD), was cloned from Mycobacterium smegmatis, and its sequence was determined
      and analyzed. A homolog of FGD which has a very high similarity to the M.
      smegmatis FGD-derived amino acid sequence was identified in Mycobacterium
      tuberculosis. FGD showed significant homology with F420-dependent N5,N10
      methylene-tetrahydromethanopterin reductase (MER) from methanogenic archaea and
      with several hypothetical proteins from M. tuberculosis and Archaeoglobus
      fulgidus, but FGD showed no significant homology with NADP-dependent glucose-6
      phosphate dehydrogenases. Multiple alignment of FGD and MER proteins revealed
      four conserved consensus sequences. Multiple alignment of FGD with the
      hypothetical proteins also revealed portions of the same conserved sequences.
      Moderately high levels of FGD were expressed in Escherichia coli BL21(DE3)
      carrying fgd in pBluescript.

PMID- 9555907
TI  - Mosaic structure of the smpB-nrdE intergenic region of Salmonella enterica.
AB  - The Salmonella enterica smpB-nrdE intergenic region contains about 45 kb of DNA
      that is not present in Escherichia coli. This DNA region was not introduced by a
      single horizontal transfer event, but was generated by multiple insertions and/or
      deletions that gave rise to a mosaic structure in this area of the chromosome.

PMID- 9555908
TI  - Temperature sensitivity of bacteriolysis induced by beta-lactam antibiotics in
      amino acid-deprived Escherichia coli.
AB  - The temperature-sensitive penicillin tolerance response previously reported in
      amino acid-deprived Escherichia coli (W. Kusser and E. E. Ishiguro, J. Bacteriol.
      169:2310-2312, 1987) was not due to the induction of the heat shock response
      resulting from a temperature upshift and was therefore unrelated to the findings
      of another report (J. K. Powell and K. D. Young, J. Bacteriol. 173:4021-4026,
      1991) indicating a positive correlation between the expression of heat shock
      proteins and penicillin tolerance. The thermosensitive event occurred in the
      lysis induction stage.

PMID- 9555909
TI  - Oxygen regulation of the ccoN gene encoding a component of the cbb3 oxidase in
      Rhodobacter sphaeroides 2.4.1T: involvement of the FnrL protein.
AB  - The ccoNOQP gene cluster of Rhodobacter sphaeroides 2.4.1T encodes a cbb3
      cytochrome oxidase which is utilized in oxygen-limited conditions for aerobic
      respiration. The beta-galactosidase activity of a ccoN::lacZ transcriptional
      fusion was low under high (30%)-oxygen and anaerobic growth conditions. Maximal
      ccoN::lacZ expression was observed when the oxygen concentration was lowered to
      2%. In an FnrL mutant, ccoN::lacZ expression was significantly lower than in the
      wild-type strain, suggesting that FnrL is a positive regulator of genes encoding
      the cbb3 oxidase.

PMID- 9555910
TI  - A novel DNA polymerase family found in Archaea.
AB  - One of the most puzzling results from the complete genome sequence of the
      methanogenic archaeon Methanococcus jannaschii was that the organism may have
      only one DNA polymerase gene. This is because no other DNA polymerase-like open
      reading frames (ORFs) were found besides one ORF having the typical alpha-like
      DNA polymerase (family B). Recently, we identified the genes of DNA polymerase II
      (the second DNA polymerase) from the hyperthermophilic archaeon Pyrococcus
      furiosus, which has also at least one alpha-like DNA polymerase (T. Uemori, Y.
      Sato, I. Kato, H. Doi, and Y. Ishino, Genes Cells 2:499-512, 1997). The genes in
      M. jannaschii encoding the proteins that are homologous to the DNA polymerase II
      of P. furiosus have been located and cloned. The gene products of M. jannaschii
      expressed in Escherichia coli had both DNA polymerizing and 3'-->5' exonuclease
      activities. We propose here a novel DNA polymerase family which is entirely
      different from other hitherto-described DNA polymerases.

PMID- 9555911
TI  - The tfdK gene product facilitates uptake of 2,4-dichlorophenoxyacetate by
      Ralstonia eutropha JMP134(pJP4).
AB  - Uptake of 2,4-dichlorophenoxyacetate (2,4-D) by Ralstonia eutropha JMP134(pJP4)
      was studied and shown to be an energy-dependent process. The uptake system was
      inducible with 2,4-D and followed saturation kinetics in a concentration range of
      up to 60 microM, implying the involvement of a protein in the transport process.
      We identified an open reading frame on plasmid pJP4, which was designated tfdK,
      whose translation product TfdK was highly hydrophobic and showed resemblance to
      transport proteins of the major facilitator superfamily. An interruption of the
      tfdK gene on plasmid pJP4 decimated 2,4-D uptake rates, which implies a role for
      TfdK in uptake. A tfdA mutant, which was blocked in the first step of 2,4-D
      metabolism, still took up 2,4-D. A mathematical model describing TfdK as an
      active transporter at low micromolar concentrations fitted the observed uptake
      data best.

PMID- 9555912
TI  - Erwinia amylovora secretes DspE, a pathogenicity factor and functional AvrE
      homolog, through the Hrp (type III secretion) pathway.
AB  - Erwinia amylovora was shown to secrete DspE, a pathogenicity factor of 198 kDa
      and a functional homolog of AvrE of Pseudomonas syringae pv. tomato. DspE was
      identified among the supernatant proteins isolated from cultures grown in an hrp
      gene-inducing minimal medium by immunodetection with a DspE-specific antiserum.
      Secretion required an intact Hrp pathway.

PMID- 9555913
TI  - Specific binding of Escherichia coli ribosomal protein S1 to boxA transcriptional
      antiterminator RNA.
AB  - We show that ribosomal protein S1 specifically binds the boxA transcriptional
      antiterminator RNAs of bacteriophage lambda and the Escherichia coli ribosomal
      RNA operons. Although S1 competes with the NusB-S10 antitermination complex for
      binding to boxA, it does not affect antitermination by the lambda N protein in
      vitro, and its role, if any, in rRNA synthesis is still unknown.

PMID- 9555914
TI  - Physiological regulation of the derepressible phosphate transporter in
      Saccharomyces cerevisiae.
AB  - The extracellular phosphate concentration permissive for the expression of
      different amounts of the active high-affinity Pho84 phosphate transporter in the
      plasma membrane as well as the PHO84 messenger RNA levels in low-phosphate-grown
      Saccharomyces cerevisiae cells is very narrow and essential for a tight
      regulation of the transporter. The Pho84 transporter undergoes a rapid
      degradation once the supply of phosphate and/or carbon source is exhausted.

PMID- 9555915
TI  - The yhhP gene encoding a small ubiquitous protein is fundamental for normal cell
      growth of Escherichia coli.
AB  - H-NS is a major constituent of the Escherichia coli nucleoid, whereas sigmaS is a
      stress-induced sigma factor. An hns null mutation affects the cellular content of
      sigmaS in such a way that a remarkable accumulation of sigmaS is observed in the
      logarithmic growth phase, which results in enhanced expression of a number of
      sigmaS-dependent genes, including the katE gene. We isolated an extragenic
      mutation that affects the expression of the katE-lacZ fusion gene in the deltahns
      background. The relevant gene was identified as yhhP, which encodes a small
      polypeptide of 81 amino acids. Lesion of this gene seemed to affect the stability
      of sigmaS. A deletion analysis of yhhP revealed that this small protein plays a
      fundamental role in the general physiology of E. coli. The yhhP-deficient cell is
      not capable of growing in standard laboratory rich medium (i.e., Luria broth),
      resulting in the formation of filamentous cells. Homologs of this intriguing
      protein occur in a wide variety of bacterial species, including archaeal species.

PMID- 9555916
TI  - Nuclease overexpression mutants of Serratia marcescens.
AB  - A family of mutants overexpressing the Serratia marcescens extracellular nuclease
      has been known for decades. A number of these alleles are characterized here at
      the molecular level, and the mutant genes are identified, yielding a likely model
      for their phenotype. The known mutations exert their effect indirectly on nucA
      expression by elevating the basal SOS response of the cell. Mutations have been
      found in xerC and uvrD, both of which result in partial SOS induction. A classic
      nucsu allele, that of strain W1050, is also likely to be in xerC.

PMID- 9555917
TI  - The Bacillus subtilis galE gene is essential in the presence of glucose and
      galactose.
AB  - Bacillus subtilis is unable to grow by consuming galactose because it is unable
      to transport it into the cell. The transcription of galE is not influenced by
      galactose but is repressed by glucose. Galactose is toxic for galE-negative
      bacteria because it results in elevated levels of metabolic intermediates. These
      negative effects are reduced in galK and galT mutants. Glucose is also toxic for
      galE-negative strains.

PMID- 9555918
TI  - Education at the crossroads: for today's practice, the DPT.

PMID- 9555919
TI  - Partial body weight support with treadmill locomotion to improve gait after
      incomplete spinal cord injury: a single-subject experimental design.
AB  - BACKGROUND AND PURPOSE: Gait training with partial body weight support has been
      used to improve gait. In this study, changes in gait relative to speed, cadence,
      stride length, and percentages of stance and swing for both lower extremities
      (LEs) during comfortable walking, fast walking, and running were studied in a
      subject with an incomplete C-5 on C-6 spinal cord injury. SUBJECT AND METHODS: A
      single-subject experimental design was used. Following a 6-week period of
      baseline measurements taken at various intervals (phase AI), the subject
      ambulated on a treadmill three times a week for 6 weeks with 32% of his body
      weight supported (phase B). Phase B was followed by a 3-week period without
      treatment during which measurements were taken at various intervals (phase AII).
      Gait variables were measured once a week during comfortable walking, fast
      walking, and running. Heart rate was monitored during treadmill training.
      RESULTS: During comfortable walking, fast walking, and running, improvements were
      seen in gait speed. During running, improvements also were seen in stride length
      and percentages of stance and swing for the right LE. The largest changes were
      recorded during running. Smaller changes were recorded during comfortable walking
      and fast walking. CONCLUSION AND DISCUSSION: These results justify testing the
      efficacy of this technique with larger groups of subjects with neurological
      impairments.

PMID- 9555920
TI  - The influence of experience with a set of simulated patients on diagnosis of
      simulated patients not previously diagnosed.
AB  - BACKGROUND AND PURPOSE: Diagnoses, to be useful, should be accurate. The purpose
      of this study using fictitious patients and student judges was to test the theory
      that diagnostic errors would occur when students saw simulated patients who were
      similar to previously seen simulated patients. SUBJECTS: Sixty physical therapist
      (PT) students and 60 non-physical therapist (NPT) students were studied. Subjects
      were assigned randomly to one of three groups. METHODS: Instructions to the three
      groups differed in terms of rules provided for diagnoses and instructions to
      remember the patients. Students first diagnosed the same eight fictitious
      patients five times. The students then diagnosed eight new patients with similar
      characteristics interspersed with the original eight patients. Half of the new
      patients had a diagnosis different from that of the most similar old patient.
      RESULTS: Students who were given a rule for diagnosis made fewer errors than
      students who were not given a rule. Students in the PT group took longer but made
      fewer errors on the critical opposite-diagnosis new cases than did students in
      the NPT group. CONCLUSION AND DISCUSSION: The results do not provide support for
      the theory that diagnostic errors would occur when students saw patients who were
      similar to previously seen patients. Students in the PT group appeared to
      emphasize accuracy at the expense of speed in making their diagnoses. Given the
      nature of the simulated patient information and the mode of presentation used in
      the experiment, however, the conclusion that therapists in actual practice do not
      make errors because of the similarity between new and previously seen patients is
      not yet warranted.

PMID- 9555921
TI  - Effects of electrical stimulation on edema formation in different strains of
      rats.
AB  - BACKGROUND AND PURPOSE: Although electrical stimulation (ES) is commonly used to
      curb edema formation, efficacy has been demonstrated in only one species of frog
      and one strain of rat. The purpose of this study was to determine whether
      different strains of rats respond differently to ES. SUBJECTS AND METHODS: Feet
      of Sprague-Dawley, Zucker-Lean, and Brown Norway rats were injured in a uniform
      manner. One foot served as a control, and the other foot received four 30-minute
      exposures to cathodal high-voltage pulsed current at amplitudes 10% less than
      those required to induce visible muscle activity. Each treatment period was
      followed by a 30-minute rest period. Limb volumes were measured before and after
      trauma and after each treatment and rest period. Changes from pretrauma volumes
      were analyzed by repeated-measures analysis of variance. RESULTS: Edema formation
      was curbed in Zucker-Lean and Brown Norway rats but not in Sprague-Dawley rats.
      CONCLUSION AND DISCUSSION: The finding that two of the three strains of rats
      responded to ES suggests that some strains of rats may be suitable models for the
      study of edema. That frogs and rats respond to high-voltage pulsed current
      suggests that humans might respond similarly.

PMID- 9555922
TI  - The relationship between head and neck posture and VDT screen height in keyboard
      operators.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of
      change in video display terminal (VDT) height from desktop height (96.5 cm [38
      in]) to an elevated position (109.2 cm [43 in]) on postural angles of the head
      and neck and the effect on cervical spine flexion moments. SUBJECTS: Twenty-seven
      persons (3 male, 24 female) who spent at least 3 hours per day using a computer
      while seated were the subjects. The subjects had a mean age of 36.7 years
      (SD=6.0, range=25-47). METHODS: Subjects were photographed over two 10-minute
      periods while seated using a computer with the VDT at two different heights.
      Later, a goniometer was used over images to record angles. RESULTS: There was no
      difference in cervical flexion moment between the two screen positions. Several
      postural angles of the head and neck showed changes, but the clinical relevance
      of these changes is questionable. CONCLUSION AND DISCUSSION: Changing the VDT
      height from 96.5 to 109.2 cm (floor to midscreen) has no effect on flexion moment
      on the cervical spine during short periods of VDT operation. If flexion moment is
      considered a biomechanical indicator of postural stress, it does not appear that
      the elevated screen position reduces postural stress on the cervical spine during
      short periods of VDT operation.

PMID- 9555923
TI  - The effect of foot structure on the three-dimensional kinematic coupling behavior
      of the leg and rear foot.
AB  - BACKGROUND AND PURPOSE: Differences in foot structures have been reported to
      account for the large variability in findings in previous studies that have
      examined the relationship between foot structure and the interdependent rotations
      of the lower extremity. The purpose of this study was to determine, in
      individuals with radiographically distinct foot structures, the effect of foot
      structure on three-dimensional kinematic behavior of the leg and rear foot during
      running. SUBJECTS AND METHODS: Based on radiographic measurements, 10
      recreational runners were assigned to a low rear-foot group and another 10
      recreational runners were assigned to a high rear-foot group. Three-dimensional
      kinematic data were collected during treadmill running. Individual axis rotations
      and the "coupled" relationship between the leg and rear-foot segments were
      defined using a Cardan angle system of three ordered rotations. RESULTS: The
      predominant rotations suggest a combined subtalar and talocalcaneal joint axis to
      favor calcaneal eversion and inversion for the low rear-foot group and tibial
      medial and lateral rotation for the high rear-foot group. Group differences were
      also found for the coupling ratio, which described the proportion of calcaneal
      eversion and inversion transferred or coupled to tibial axial rotation.
      CONCLUSION AND DISCUSSION: The rotational patterns and coupling response unique
      to each foot group may enhance our understanding of lower-extremity injuries
      related to certain foot structures. An assessment of the coupling relationship in
      combination with traditional frontal-plane measurements may better guide
      decisions regarding selection of footwear and orthoses.

PMID- 9555924
TI  - Aerobic exercise for a patient with chronic multisystem impairments.
AB  - Many patients with long-term disabilities have inactive lifestyles that put them
      at risk for chronic diseases and secondary disabilities. The purpose of this case
      report is to illustrate the process of aerobic exercise prescription for a
      patient with chronic multisystem impairments. The patient was a 43-year-old man
      who incurred a traumatic brain injury and multiple fractures in a motorcycle
      accident 15 years previously. He subsequently developed heterotopic ossification
      around the right hip. In addition, the patient had a history of smoking. We chose
      a "nontraditional" mode of exercise for the patient that we believed would be
      safe and effective and would accommodate his neurologic and orthopedic
      impairments. The mode of exercise used was an apparatus in which the upper and
      lower extremities alternately flexed and extended in a nonreciprocal fashion. The
      patient attended 12 exercise sessions over a 1-month period, during which he
      demonstrated acute and chronic physiological responses appropriate for the
      exercise stimulus.

PMID- 9555925
TI  - Clinical reasoning in the management of a 21-year-old physical therapist student
      with chronic hip pain.

PMID- 9555926
TI  - Referral pattern and outcome in men and women undergoing coronary artery bypass
      surgery--a critical review.
AB  - Women with coronary artery disease are less likely to undergo coronary artery
      bypass surgery, and this may represent a potential referral bias in favor of men.
      A higher in-hospital mortality rate in women compared with men has been reported
      earlier. Accumulating evidence currently suggests, however, that variables other
      than gender, such as advanced age, late referral, angina classification, diabetes
      mellitus, concurrent medical conditions, the number of diseased vessels, the
      caliber of coronary arteries, and the decreased body surface area in women may
      have accounted for this difference. In fact, when these variables are taken into
      account, female gender is no longer a statistically significant predictor of
      operative mortality. Women appear to have comparable immediate and late survival
      rates. Recurrent angina, perioperative myocardial infarction, congestive heart
      failure, incomplete revascularization, and early and late graft reocclusion
      following surgery are, however, more prevalent in women. Men and women show
      differences in recovery experiences after discharge following bypass surgery.
      When coronary bypass surgery is offered to women, the decision should be
      individualized, based on the patients' perioperative baseline clinical risk
      factors and coronary anatomy. Coronary artery bypass surgery should not be
      withheld in women who are considered to be appropriate candidates for fear of a
      reduced success rate.

PMID- 9555927
TI  - Use of nuclear magnetic resonance imaging angiography to follow-up arterial
      remodeling in an animal model.
AB  - Appropriately sized arteries in small animals may be possible models for studying
      the remodeling process as occurs after arterial balloon injury in humans.
      Magnetic resonance imaging (MRI) is able to noninvasively image tissue in vivo.
      To date, small animal angiography models have mostly used research-dedicated
      instruments and resolution, which are not universally available. Experiments were
      carried out on a rat aorta model of remodeling in vivo (n=40). Arteries were
      injured by oversized balloon dilation; control arteries were uninjured.
      Angiography imaging was performed immediately before sacrifice with an unmodified
      clinical MRI unit, a 1.5 Tesla MR tomograph with a 20-cm-diameter coil.
      Longitudinal MRI pictures of the aorta and morphometry of tissue sections to
      measure luminal and arterial wall areas were analyzed with use of computer
      assisted techniques. Comparison of dimensions demonstrated correlation between
      MRI and histology measurements of the lumen. MRI and morphometry showed a gradual
      increase in mean luminal area over 6 weeks following injury. The lumen increase
      correlated with total arterial area and thickness. In this rat aorta model,
      remodeling documented at histology was followed-up in vivo. The use of such
      clinical MRI scanners has potential to reduce animal numbers needed to follow-up
      the remodeling process after therapeutic intervention.

PMID- 9555928
TI  - A comparative evaluation of femorofemoral crossover bypass and iliofemoral bypass
      for unilateral iliac artery occlusive disease.
AB  - The purpose of this study was to compare the results of extra-anatomic
      femorofemoral crossover bypass grafting to the anatomic iliofemoral bypass
      grafting procedure in the treatment of patients with unilateral iliac artery
      occlusive disease with respect to patency and limb salvage. The records of all
      patients with unilateral iliac artery disease who underwent revascularization
      between January 1988 and December 1995 at the University of Iowa Hospitals and
      Clinics (UIHC) were retrospectively reviewed; 108 patients were identified and
      divided into two groups. Group I (n=68; male/female=44/24) was composed of all
      patients who underwent a femorofemoral crossover extra-anatomic bypass. All
      patients who underwent an iliofemoral anatomic bypass constituted group II (n=40;
      male/female=24/16). The mean age for group I was 60 years (range 28-87) and for
      group II, 54 years (range 14-86). The medical risk factors between both groups
      were comparable. Except for the higher incidence of gangrene in group II the
      indications for surgery were comparable between both groups. A
      polytetrafluoroethylene graft was used in 88% of group I patients and in 90% of
      group II patients (NS). In the remaining patients, an autogenous vein conduit was
      used. Two patients from group I (2.9%) died in the perioperative period (NS).
      Graft patency was assessed by clinical evaluation, Doppler-derived ankle/brachial
      indices, and color duplex imaging. The cumulative primary and secondary patency
      rates, limb salvage, and patient survival were calculated by use of life table
      analysis (SE<0.1). The need for simultaneous outflow and inflow procedures at the
      time of surgery was comparable between both groups. The proportion of patients
      who underwent further revascularization during follow-up was also comparable. The
      5-year primary and secondary graft patency rates were 81.7% and 90.3%, in group I
      and 61.3% and 80.5% in group II. Although the difference between both groups was
      not significant there was a tendency toward higher rates with femorofemoral
      bypass. The 5-year survival rates of 80.3% for group I and 73.3% for group II
      were comparable. These data suggest that there is no significant difference in
      the long-term results between the femorofemoral crossover bypass grafts and
      iliofemoral grafts. Both procedures result in acceptable patency and limb salvage
      rates. The femorofemoral bypass is, however, more attractive, for it can be
      performed under local anesthesia if needed and does not involve the creation of
      the retroperitoneal incision necessary with the iliofemoral bypass.

PMID- 9555930
TI  - Entering the ninth decade is not a contraindication for carotid endarterectomy.
AB  - The role of carotid endarterectomy (CEA) in stroke prevention is now better
      defined. However, its role in patients older than 79 years of age is
      controversial. This group of patients has been excluded in most clinical trials.
      In this study the authors reviewed their experience with CEA patients >79 years
      old. The records of all patients older than 79 years of age who underwent a CEA
      in a recent time period from January 1988 to December 1996 were retrospectively
      reviewed. Forty-one patients (31 men, 10 women) were identified by computer
      search. The indication for operation included transient ischemic attack in 12
      (29.3%), amaurosis fugax in nine (22%), stroke in two (4.9%), and nonhemispheric
      symptoms in three (7.3%). Fifteen patients (36.6%) were asymptomatic. Medical
      risk factors included coronary artery disease in 26 (63.4%), hypertension in 22
      (53.7%), and smoking in 12 (29.3%). The procedure was performed under EEG
      monitoring in all patients. General anesthesia was administered in 37 (90%) and
      regional anesthesia in four (10%). Shunts were used in four (10%) patients. The
      internal carotid artery was patched in 16 patients (39%). One patient (2.4%)
      developed a perioperative stroke and only one patient developed perioperative
      myocardial infarction (MI). None of the patients died within 30 days of surgery.
      In addition to the one MI case, five patients developed minor complications. The
      average length of time for stay after CEA was 3.4 days. Patients were followed up
      for an average of 20.7 months. Six patients died during follow-up. Four of those
      died from an MI and two from a stroke. The authors conclude that with proper
      selection of patients, CEA is safe in the octogenarian. Age alone should not be a
      contraindication for CEA.

PMID- 9555929
TI  - Acute mesenteric ischemia after open heart surgery.
AB  - Acute mesenteric ischemia is a rare but severe complication after open heart
      surgery. Its incidence (0.2-0.4%) is quite low, but mortality rates are ranging
      between 70% and 100%. From October 1992 to December 1996, 4,640 patients
      underwent open heart surgery with cardiopulmonary bypass: 74.6% coronary artery
      bypass graft (CABG) operations, 23.2% valve replacement including aortic repairs,
      and 2.2% corrections of congenital heart diseases or tumors of the heart. The
      overall mortality rate (30 days) was 3.4%, and after CABG, 2.9%. Twelve patients
      (0.26%), following CABG (one combined with aortic valve replacement, one with
      mitral reconstruction, and one with carotid disobliteration) developed signs of
      acute mesenteric ischemia in the early postoperative period (day 1 to 5). In all
      patients various abdominal symptoms, leukocytosis, acidosis, hyperlactatemia,
      hyperosmolality, renal failure, and, finally, hemodynamic instability were
      observed. Eleven patients underwent emergency laparotomy. Mesenteric angiography
      was done if possible in still stable patients (n=7); it showed severe stenosis or
      occlusion prior to the operation in each case. Other diagnostic methods were not
      reliable. In six patients (55%) during the first look, extensive bowel necrosis
      was found and in five patients an ischemic intestine but no necrosis was
      detected. Of these, three patients were affected by extensive bowel gangrene at
      the second look. In the fourth patient a disseminated peripheral ischemia of the
      entire small intestine was found intraoperatively. After mechanical release and
      stimulation normal bowel function could be reestablished. One patient underwent
      percutaneous transluminal angioplasty prior to the laparotomy. Bowel perfusion
      was still deteriorated but no necrosis was found intraoperatively. These patients
      were the only survivors in the investigated group; 10 of 12 patients (83.3%) died
      in the early postoperative period (day 1 to day 6). Predisposing factors for
      mesenteric ischemia are: arteriosclerotic patients after CABG (100%), age >70
      years (91.7%), hyperosmotic dehydration (100%), and cardiac ischemia in 25%.
      Mesenteric ischemia is a fatal complication with high mortality rates after open
      heart surgery, especially in older, dehydrated patients with generalized
      atherosclerotic vessel disease. As the acute mesenteric ischemia usually starts
      during anesthesia or in the early postoperative period, setting of immediate
      diagnosis is very difficult. With the occurrence of typical symptoms diagnostic
      and therapeutic procedures (angiography and laparotomy) must be done very
      urgently owing to the life-threatening mesenteric process. When mesenteric
      gangrene already has taken place, the prognosis is very poor, despite extensive
      resection. Prevention can be exercised by avoiding perioperative hyperosmotic
      dehydration of patients at high risk.

PMID- 9555931
TI  - Carotid-subclavian bypass for subclavian artery revascularization: long-term
      follow-up and effect of antiplatelet therapy.
AB  - Subclavian artery stenosis is found in up to 25% of supraaortic lesions. Bypass
      grafting is the procedure of choice but controversies exist concerning the
      optimal technique and the effect of postoperative antithrombotic therapy on long
      term patency. The authors retrospectively analyzed 40 patients with carotid
      subclavian bypasses. Stenoses were documented preoperatively by arteriography.
      Patency was determined by clinical, ultrasound, or arteriographic examinations.
      Cumulative patency rates were calculated by Kaplan-Meier method and analyzed by
      Tarone-Ware test. Graft materials were Dacron (32), polytetrafluoroethylene
      (seven) or saphenous vein (one). Indications for surgery included vertebrobasilar
      insufficiency (22.5%), upper extremity ischemia (22.5%), and the combination of
      both (55.0%). Perioperative mortality and morbidity were 2.5% and 10.0%,
      respectively. Patients were followed up from 0 to 134 months (mean 61+/-39
      months). Cumulative 5-year patency rate was 83.3%. Anticoagulation with
      acetylsalicylic acid (ASA) led to significantly better 5-year patency rates
      (100%) as compared with the combination of ASA and dipyridamole (64.0%, p=0.013)
      or no anticoagulation (70.0%, p=0.016). Carotid-subclavian bypass led to
      excellent long-term patency rates and can provide durable relief of symptoms with
      minimal perioperative morbidity and mortality. Therefore, it is a worthwhile
      procedure to correct proximal subclavian artery stenosis. Postoperative
      medication with ASA seems to increase long-term bypass function significantly.

PMID- 9555932
TI  - Effect of coacervated alpha-elastin on proliferation of vascular smooth muscle
      and endothelial cells.
AB  - The arterial wall injury associated with arterial graft implantation causes
      smooth muscle cells (SMCs) in the media to migrate and proliferate in the intima
      at the graft-artery junction resulting in anastomotic intimal hyperplasia (AIH).
      An important step in developing a small-diameter prosthesis may be to stimulate
      endothelialization and thereby inhibit AIH. In this study, we investigated the
      effect of coacervated and crosslinked alpha-elastin on proliferation of SMCs and
      endothelial cells (ECs) in vitro. Coacervation is an important step in the
      conversion of proelastin to make an elastin fiber in vivo. SMCs and ECs were
      prepared from porcine aortic media and endothelium, respectively. SMCs and ECs
      (three to five passages, 4 x 10[4] cells/well) were seeded onto 12 well plates,
      coated and crosslinked with 0 or 10 mg/mL of coacervated alpha-elastin. After the
      1st, 2nd, or 3rd day of cultivation, proliferation was assayed by scintillation
      counting of [3H]-thymidine incorporation. For the 4th day only, 0, 0.1, 1, 10
      mg/mL concentration of coacervated alpha-elastin was coated and crosslinked. SMC
      proliferation (1st, 2nd day: p<0.005; 3rd, 4th day: p<0.0001) was significantly
      inhibited over time and dose dependently, eg, 0.1 mg/mL (45.7+/-2.3%: % of
      control p<0.005), 1 mg/mL (5.9+/-0.7%, p<0.0005), 10 mg/mL (2.8+/-0.4%,
      p<0.0005). EC proliferation was inhibited over time by 10 mg/mL of coacervated
      alpha-elastin (2nd, 3rd day: p<0.005; 4th day: p<0.0001), but proliferation
      (132.8+/-9.9%: % of control p=NS) was stimulated by 0.1 mg/mL of coacervated
      alpha-elastin. These results suggest that coating and crosslinking a coacervated
      alpha-elastin into the structure of arterial prosthesis may inhibit AIH and
      stimulate endothelialization.

PMID- 9555933
TI  - Experimental study of cardiac lymph dynamics and edema formation in
      ischemia/reperfusion injury--with reference to the effect of hyaluronidase.
AB  - This study is designed to evaluate the effect of hyaluronidase on the canine
      myocardial edema derived from ischemia/reperfusion injury. The mongrel dog's
      heart received 90 minutes of ischemia under cardiopulmonary bypass consisting of
      30 minutes of normothermia alone and 60 minutes of hypothermia with cardioplegic
      arrest. Reperfusion for 60 minutes was added thereafter. Two kinds of
      cardioplegic solution, 4 degrees C St. Thomas' Hospital solution with or without
      3000 units/L of hyaluronidase, were prepared. The solution was given antegradely
      every 30 minutes during cardioplegic arrest. Cardiac lymph was collected
      continuously from the afferent duct of the cardiac lymph node by cannulation.
      Hyaluronidase in the cardioplegic solution increased cardiac lymph volume
      significantly and improved postischemic recovery of cardiac function. A high
      level of adenosine triphosphate was maintained at that time. The myocardial water
      content at the end of reperfusion revealed a minimum increase with hyaluronidase
      use. Active drainage of cardiac lymph by hyaluronidase alleviates the myocardial
      edema formation, thereby preserving cardiac function.

PMID- 9555934
TI  - The determination of metabolite M17 and its meaning for immunosuppressive
      cyclosporin therapy.
AB  - Cyclosporin A (CyA) is intensively metabolized by the hepatic cytochrome p450 III
      monooxygenase A system in the human liver, the most important metabolites being
      M1, M17, and M21. Because CyA and its metabolites have nephrotoxic, hepatotoxic,
      and neurotoxic side effects, CyA dosage must be calculated to avoid the risk of
      organ rejection through underdosage and toxic organ damage through overdosage or
      accumulation of metabolites. In this study, we determined the whole-blood
      concentrations of cyclosporin and metabolite M17 by high-pressure liquid
      chromatography (HPLC) and by monoclonal specific and polyclonal nonspecific
      fluorescence polarization immunoassay (Abbott) in patients after
      immunosuppressive treatment. Patients with different resorption and
      metabolization rates showed high individual variations. CyA concentrations in
      patients with good liver function and low concentrations of CyA metabolites
      showed a good correlation between the HPLC and the FPIA (TDx-monoclonal assay)
      methods in ranges between 25 and 180 ng/mL. TDx-monoclonal was not always as
      precise as HPLC. In cases of metabolic disorders, we found false high CyA
      concentrations assayed with the immunologic method, caused by a crossreaction of
      the elevated metabolite concentration. We found that HPLC rendered more
      information about the extent of immunosuppressive activity and the metabolization
      rate and showed a good correlation with the concentration of metabolite M17 and
      total metabolites measured with the Abbott CyA polyclonal kit.

PMID- 9555935
TI  - Arm edema, subclavian thrombosis, and pacemakers--a case report.
AB  - This reports an arm edema that was initially treated as cellulitis and later
      diagnosed to be subclavian thrombosis due to pacemaker wire irritation. We
      present an 87-year-old Caucasian man with 5 weeks duration of left arm swelling
      and pain that was treated with two courses of antibiotics. An axillary venous
      Doppler study was interpreted as normal with no evidence of venous thrombosis.
      However, a venogram showed evidence of thrombosis involving the left innominate,
      subclavian, and axillary veins with multiple collateral veins diverting the blood
      to the contralateral side and into the superior vena cava. Intravenous
      anticoagulation was initiated and subsequently the patient was maintained on
      warfarin (Coumadin). The thrombosis subsequently improved and the original
      pacemaker was maintained. Arm edema are commonly mistaken for cellulitis, causing
      a delay in a more definite diagnosis of subclavian thrombosis. In a setting of a
      patient with pacemaker, subclavian thrombosis should be considered even with a
      normal screening venous ultrasound test. The incidence, manifestation, venous
      Doppler, and venogram findings are reviewed and discussed. Upper arm edema and
      superior vena cava syndrome are the most common presentation of this subclavian
      thrombosis associated with pacemakers. Venous ultrasound tests may be normal and
      a venogram is usually required to establish a diagnosis.

PMID- 9555936
TI  - Considerations in the surgical management of ventricular septal defect and aortic
      insufficiency--a case report.
AB  - A 23-year-old man presented with progressive exercise-related dyspnea and easy
      fatigability. He gave a history of a murmur of aortic insufficiency since
      childhood. Cardiac catheterization demonstrated severe aortic insufficiency. At
      surgery the patient was found to have prolapse of the right coronary cusp into a
      significant supracristal ventricular septal defect. Repair was carried out with a
      Dacron patch closure of the septal defect and replacement of the valve with a 29
      mm St. Jude valve. The patient recovered uneventfully and is fully active and
      employed 5 years later. Review of the literature documents that this is an
      uncommon lesion. The approaches to preoperative diagnosis include transesophageal
      echo. The management techniques have included ventricular septal defect closure,
      alone and with valvuloplasty, and septal defect closure with aortic valve
      replacement. The anatomic and patient characteristics guide selection of the most
      suitable management of these patients.

PMID- 9555937
TI  - Genetically modified mice for the study of apolipoprotein B.
AB  - Over the past five years, several laboratories have used a variety of transgenic
      and gene-targeted mice to study apoB. These studies have helped in 1) generating
      new mouse models suitable for investigating the genetic and environmental factors
      affecting atherogenesis; 2) providing systems for investigating apoB
      structure/function relationships; 3) understanding the regulation of apoB gene
      expression in the intestine; 4) delineating a critical role for apoB expression
      in mouse embryonic development; 5) yielding insights into the "physiologic
      rationale" for the existence of the two different forms of apoB, apoB-48 and apoB
      100, in mammalian metabolism; and 6) providing basic insights into mechanisms
      involved in the human apoB deficiency syndrome, familial hypobetalipoproteinemia.

PMID- 9555938
TI  - Adipose tissue ob mRNA expression in humans: discordance with plasma leptin and
      relationship with adipose TNFalpha expression.
AB  - Elevated plasma leptin levels are found in obese humans, suggesting a defect in
      the function of leptin in regulating body weight and adiposity. In 53 subjects
      covering a broad range of adiposity, we examined the relationships between plasma
      leptin, adipose tissue ob mRNA levels, and adipose tissue TNF mRNA. There was a
      highly significant correlation between plasma leptin levels and every index of
      adiposity. In contrast, the relationship between ob mRNA levels and adiposity was
      weak. Adipose tissue from obese subjects demonstrated higher ob mRNA levels than
      adipose tissue from lean subjects (lean: 0.49+/-0.05; obese 0.87+/-0.09 arbitrary
      units, P< 0.05). However, there was no significant correlation between body fat
      and ob mRNA level. In addition, there was no significant relationship between ob
      mRNA levels and plasma leptin levels, which were measured in the same subjects.
      In addition to the measure of ob mRNA levels, adipose TNF mRNA levels were
      measured in 18 subjects. TNF mRNA levels varied with ob mRNA levels (r = 0.44, P
      = 0.06). These data show that plasma leptin levels are not directly related to
      adipose tissue ob mRNA levels, suggesting posttranscriptional regulation of
      leptin expression, either at the level of the adipocyte, or by alteration of
      plasma leptin degradation or clearance. In addition, the parallel changes in ob
      and TNF mRNA in adipose tissue suggest that these two important factors in the
      defense against obesity may be regulated similarly.

PMID- 9555939
TI  - Secretion of apoB- and apoA-I-containing lipoproteins by chick kidney.
AB  - Previous studies showed that chick kidney is a site of synthesis of
      apolipoprotein (apo) B(B-100) and A-I. Aims of the present study were: a) to
      compare apoB and apoA-I production in chick kidney and liver; b) to investigate
      whether kidney apolipoproteins were secreted as constituents of lipoproteins; and
      c) to define the cellular sites of renal apolipoprotein synthesis. Kidney and
      liver slices taken from the same animals were incubated with 35S-labeled amino
      acids and radioactive apoB and apoA-I were immunoprecipitated from cell
      homogenate and incubation medium. The percentage of total protein radioactivity
      incorporated into cell plus medium apoB and apoA-I was 0.23+/-0.08 and 0.19+/
      0.11 in kidney and 0.38+/-0.05 and 0.38+/-0.07 in liver, respectively (P < 0.05
      kidney vs. liver). 35S-labeled medium lipoproteins were separated by density
      gradient ultracentrifugation and three major classes corresponding to VLDL + IDL,
      LDL, and HDL were identified. Most of the apoB secreted by the liver was found in
      VLDL, IDL, and LDL whereas kidney apoB was found in VLDL, LDL and "light" HDL (d
      1.070-1.130 g/ml). In both hepatic and renal lipoproteins apoA-I was found not
      only in HDL but also in the other lipoproteins. Immunohistochemical analysis of
      kidney sections showed that apoB and apoA-I were present almost exclusively in
      the epithelial cells of proximal and distal convoluted tubules. Thus apoB and
      apoA-I synthesized by the epithelial cells of the proximal and distal convoluted
      tubules of chick kidneys are secreted as constituents of lipoprotein particles
      floating within the density range of plasma lipoproteins. These observations
      suggest that in the chick, the kidneys may contribute to the plasma lipoprotein
      pool.

PMID- 9555940
TI  - Gene transcription of the retinoid X receptor alpha (RXRalpha) is regulated by
      fatty acids and hormones in rat hepatic cells.
AB  - This work describes the molecular mechanisms of fatty acid and hormonal
      modulations of the retinoid X receptor alpha (RXRalpha) in rat liver cells. We
      examined the effects of different fatty acids (myristic, stearic, oleic,
      linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and
      several hormones (the glucocorticoid analogue dexamethasone, insulin, and
      retinoic acid) on the RXRalpha mRNA and protein levels in rat hepatoma cells and
      cultured hepatocytes. The fatty acids induced the RXRalpha gene expression
      resulting in up to 3-fold induction. Dexamethasone alone induced the mRNA level
      and, in combination with fatty acids, an additive or synergistic effect was
      observed. The dexamethasone-increased mRNA level was obliterated by insulin. The
      same pattern of regulation of the protein level was observed when determined in
      cultured hepatocytes, but the induced protein level showed a lower magnitude of
      stimulation than the mRNA level. This could indicate a post-transcriptional
      modulation of the RXRalpha gene expression. Time course studies showed a maximal
      induction of mRNA and protein levels after 18 h and 48 h, respectively. Our
      results uniformly show that the RXRalpha gene expression is under distinct
      regulation by fatty acids and hormones which suggests a coupling with the lipid
      metabolizing system and the hormonal signaling pathway.

PMID- 9555941
TI  - Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on
      the interaction of LDL with human macrophages.
AB  - Most models of lipoprotein oxidation by free radicals have excluded
      macromolecular plasma components from the system. This limits their biological
      significance because oxidation of lipoproteins appears to occur in the intima in
      the presence of a plasma ultrafiltrate. Hemin, a product of in vivo hemoglobin
      degradation, binds and oxidizes purified lipoproteins. However, it is not known
      whether this occurs in the presence of plasma components that may sequester
      hemin. We found that hemin in serum diluted to protein levels of the
      extracellular fluid (10-30%) binds to low and high density lipoproteins (LDL,
      HDL) with association constants in the nmol/L range. In the presence of H2O2,
      hemin oxidizes both lipoproteins in diluted serum with formation of conjugated
      dienes, thiobarbituric acid reacting substances, and F2-isoprostanes. This
      appeared to be caused by the high affinity of hemin with LDL and by the Fe3+
      liberated that remains associated with the particles after hemin is degraded.
      Spectrophotometric and fluorescence experiments and electrophoresis of porphyrins
      complex with LDL indicated that the heme ring is buried in the lipoprotein
      surface-monolayer with the carboxylic groups in contact with positive regions of
      the protein and the solvent. Human macrophages associated and degraded 3- to 4
      times more hemin-oxidized LDL in diluted serum than native LDL. It is possible
      then that at sites of LDL, accumulation in the extracellular intima, hemin and
      H2O2 production could cause oxidation with potential atherogenic consequences for
      cellular lipoprotein processing. This may occur even when other macromolecules of
      the extracellular fluid are present.

PMID- 9555942
TI  - Synergistic activation of transcription by nuclear factor Y and sterol regulatory
      element binding protein.
AB  - The current studies define the role of three distinct cis-elements in the
      proximal promoter of the rat farnesyl diphosphate (FPP) synthase gene. The three
      cis-elements, a sterol regulatory element 3 (SRE-3) flanked by an ATTGG motif
      (inverted CCAAT box), and a CCAAT box, form a sterol regulatory unit that is
      necessary and sufficient for sterol-regulated expression of FPP synthase promoter
      reporter genes. FPP synthase promoter-reporter genes, that contain promoters with
      either wild-type nucleotide sequences or mutations in one or more of the three
      cis-elements, were transiently transfected into CV-1 cells. The activity of the
      wild-type promoter-reporter gene increased when the cells were incubated in
      sterol-depleted media or when the cells were co-transfected with a plasmid
      encoding the mature form of SRE binding protein (SREBP-1a). The results with the
      mutant promoter-reporter genes demonstrated that all three cis-elements were
      necessary for normal expression/regulation of the reporter gene by either sterols
      or by co-expressed SREBP-1a. Gel mobility shift assays demonstrated that the
      synergistic binding of SREBP-1a to SRE-3 was dependent on the binding of
      recombinant nuclear factor Y (NF-Y) to the DNA, consistent with the in vivo
      regulation studies.

PMID- 9555943
TI  - Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and
      VLDL.
AB  - Mouse and hamster SR-BI glycoproteins and their putative human counterpart CLA-I
      are so far the only scavenger receptors known to bind both native and modified
      lipoproteins. CD36, a multigland glycoprotein structurally related to SR-BI and
      CLA-1, has been reported to bind oxidized low density lipoprotein (OxLDL) and
      acetylated LDL (AcLDL). In this report, we have studied the ability of CD36 to
      bind native lipoproteins. By transient expression of human CD36 in mammalian and
      insect cells, we demonstrate that CD36 is a high affinity receptor for the native
      lipoproteins HDL, LDL, VLDL, and, as previously reported, for OxLDL and AcLDL.
      The specificity of these interactions is supported by the dose-dependent
      inhibiton, effect of a monoclonal antibody against CD36. Furthermore, at least
      for HDL, binding to CD36 does not require the presence of apoE. These findings,
      together with preferential expression of CD36 in tissues performing very active
      fatty acid metabolism (skeletal muscle, heart, mammary epithelium, and adipose
      tissue) and its involvement in foam cell formation (macrophages), suggest that
      binding of lipoproteins to CD36 might contribute to the regulation of lipid
      metabolism, and to the pathogenesis of atherosclerosis.

PMID- 9555944
TI  - Binding and intracellular trafficking of lipoprotein lipase and triacylglycerol
      rich lipoproteins by liver cells.
AB  - The cellular mechanisms and pathways by which lipoprotein lipase (LPL) enhances
      the binding and uptake of lipoproteins remains unknown. Confocal and
      immunoelectron microscopy demonstrated that primary binding of bovine LPL (bLPL)
      occurs at the microvilli surface of HepG2 cells and hepatocytes. Internalized
      bLPL was associated with endocytic vesicles and multivesicular bodies.
      Quantitative immunofluorescence indicated that the presence of bLPL caused a
      marked increase in the cell-surface binding of DiI-conjugated triacylglycerol
      rich lipoproteins (DiI-TRL). Confocal microscopy showed that when DiI-TRL was
      incubated with bLPL at 4 degrees C, the distributions of bound LPL and DiI-TRL
      were totally coincident, and covered the apical surface of both HepG2 cells and
      hepatocytes. When incubated separately, the time-courses of the internalization
      of fluorescence associated with DiI-TRL and bLPL were different: DiI-TRL was
      quickly internalized by both HepG2 cells and hepatocytes, and reached a plateau
      at 30 min, whereas intracellular LPL increased continuously, but more slowly in
      the same period. In the presence of bLPL, DiI-TRL was internalized progressively
      by HepG2 and by cultured hepatocytes for up to 1 h and no saturation was reached.
      At this time the intensity of labeling of bLPL was lower than of DiI-TRL and a
      higher number of DiI spots did not colocalize with bLPL immunofluorescence,
      suggesting that the ligands follow a different pathway after internalization. The
      data suggest that when lipoprotein lipase (LPL) is associated with the
      lipoproteins it directs them to specific endocytic pathways. A hypothetical model
      of the intracellular pathways followed by triacylglycerol-rich lipoproteins and
      LPL after internalization is proposed.

PMID- 9555945
TI  - Characterization of recombinant human plasma lecithin: cholesterol
      acyltransferase (LCAT): N-linked carbohydrate structures and catalytic
      properties.
AB  - The major N-linked carbohydrate structures were determined for recombinant human
      plasma lecithin:cholesterol acyltransferase (LCAT). The analysis of the structure
      of oligosaccharides by fast atom bombardment mass spectrometry (FAB-MS) and
      linkage analysis was preceded by reduction and carboxymethylation of the intact
      glycoproteins and digestion with trypsin and proline specific endopeptidase. The
      N-glycans were subsequently released from the glycopeptides by PNGase F digestion
      and the oligosaccharides were separated using a C18 Sep-pak cartridge. The data
      from the combination of FAB spectrometry and linkage analysis show that the N
      linked glycans present on recombinant LCAT (rLCAT) were composed primarily of
      triantennary and tetraantennary structures with and without core fucosylation. A
      minor population of glycans (less than 5%) contained up to three repeats of N
      acetyllactosamine in one or more antennae. The LCAT activities of both
      recombinant and circulating forms of plasma LCAT were determined using low
      molecular weight and lipoprotein substrates. The catalytic behavior of these two
      enzyme forms were found to be very similar if not identical. These findings
      validate the concept that the recombinant enzyme can serve as an appropriate
      model for structure/function studies of LCAT and provide the foundation for
      subsequent structural studies.

PMID- 9555946
TI  - The carboxy-terminal region of human lipoprotein lipase is necessary for its exit
      from the endoplasmic reticulum.
AB  - Certain missense substitutions on the human lipase (hLPL) gene produce mutated
      proteins that are retained in different compartments along the secretory pathway.
      The purpose of the present study was to elucidate whether the C-terminal domain
      of the hLPL molecule could be important for secretion. We constructed by site
      directed mutagenesis three carboxy-terminal mutated (F388-->Stop, K428-->Stop and
      K441-->Stop) hLPL cDNAs that were expressed in COS1 cells. Immunoblotting of cell
      extracts showed that all three constructs led to similar levels of protein. Both
      wild type (WT) hLPL and the truncated K441-->Stop hLPL were secreted to the
      extracellular medium, and presented a similar intracellular distribution pattern
      as shown by immunofluorescence. Neither F388-->Stop nor K428-->Stop hLPL protein
      was detected in cell medium. Immunofluorescence experiments showed that both
      truncated hLPL were retained within an intracellular compartment, which became
      larger. Double immunofluorescence analysis using antibodies against LPL and
      antiprotein disulfide isomerase as a marker showed that the truncated K428-->Stop
      hLPL was retained within the rough endoplasmic reticulum. This truncated protein
      was not found in other compartments in the secretory pathway, such as Golgi
      complex and lysosomes, indicating that it did not exit the endoplasmic reticulum.
      Further analysis of the C-terminal region of the LPL molecular model showed both
      that F388-->Stop and K428-->Stop hLPL truncated proteins are highly hydrophobic.
      As retention of secretory proteins in the rough endoplasmic reticulum is a
      quality control mechanism of the secretory pathway, we conclude that the C
      terminal domain of hLPL is critical for correct intracellular processing of the
      newly synthesized protein.

PMID- 9555947
TI  - Uncoupling protein-1 mRNA expression in obese human subjects: the role of
      sequence variations at the uncoupling protein-1 gene locus.
AB  - Uncoupling protein-1 (UCP-1) activity in brown adipose tissue increases
      thermogenesis, contributes to facultative energy expenditure in humans, and has
      been implicated in the pathogenesis of rodent obesity. To determine genetic
      factors controlling UCP-1 expression in humans, we measured intra- and
      extraperitoneal UCP-1 mRNA abundance levels by a competitive RT-PCR method and
      compared expression levels with common sequence variations in the beta3
      adrenergic receptor gene and the distal UCP-1 gene promoter in obese human
      subjects. While median and average UCP-1 mRNA levels in both the intra- and
      extraperitoneal tissue were lower in subjects heterozygous for the Trp64Arg
      mutation in the beta3-adrenergic receptor gene, this difference was not
      statistically significant. However, a strong association of intraperitoneal UCP-1
      mRNA abundance with the UCP-1 gene polymorphism at -3826 relative to the
      transcription start site was observed that explained 19.3% of the interindividual
      variability. The minor allele imparted a dose-dependent reduction on UCP gene
      expression. The importance of sequence variations at the UCP-1 gene locus as a
      common source of UCP-1 mRNA abundance variability was supported by allele
      specific expression studies utilizing a newly identified polymorphism in exon 2
      of the UCP-1 gene that predicts a substitution of alanine by threonine. In four
      subjects heterozygous for the -3826 polymorphism, the mRNA species transcribed
      from the wild-type allele accounted for 63+/-6% percent of total intraperitoneal
      mRNA abundance. In one subject homozygous for the minor promoter allele, wild
      type mRNA was also more abundant than variant mRNA. Thus, the UCP-1 polymorphism
      at -3826 is probably only a marker for a frequent mutation causing reduced mRNA
      expression.

PMID- 9555948
TI  - Chylomicron remnant uptake is regulated by the expression and function of heparan
      sulfate proteoglycan in hepatocytes.
AB  - Chylomicron remnants transport cholesterol from the intestine, and are removed
      from the circulation principally by the liver. While hepatic receptors, including
      the low density lipoprotein (LDL) receptor account for endocytosis, heparan
      sulfate proteoglycans (HSPG) participate in the initial binding of remnants to
      liver cells. To explore the interactions between HSPG and endocytosis of
      remnants, in the present study the expression of HSPG was inhibited in HepG2
      cells transfected by a synthetic antisense oligodeoxynucleotide SYN5.
      Immunofluorescent staining by a monoclonal anti-syndecan antibody showed
      significant reduction in the expression of syndecan in SYN5-treated cells
      compared with control cells. Remnant binding decreased by about 50-70% in SYN5
      transfected cells. Monoclonal antibodies to either heparan sulphate or the LDL
      receptor decreased binding by about 60-65%. The glycosylation inhibitor beta
      nitrophenylxylopyranoside inhibited remnant uptake by 25%, whereas 4-nitrophenyl
      beta-D-galactopyranoside had no effect on remnant binding. Heparinase completely
      abolished binding at appropriate concentrations. Heparitinase was less effective
      than hep arinase in inhibiting remnant binding. Suramin completely abolished the
      remnant binding. Poly-arginine, poly-lysine, and protamine all reduced remnant
      uptake by the cells, as did polybrene, a synthetic polycation, suggesting a role
      of cation-anion interactions in remnant binding. Brefeldin A, colchicine, and
      monensin caused the fluorescence associated with remnants to persist within the
      cells, confirming that blockers of tubulovesicular processes and Golgi function
      inhibit the intracellular transport and degradation of the remnants. Our results
      show that remnant binding to liver cells depends on the LDL receptor, on the
      expression of HSPG core proteins, and on the functionality of heparan sulfate in
      HSPG.

PMID- 9555949
TI  - In vitro factors affecting the concentration of gamma-LpE (gamma-LpE) in human
      plasma.
AB  - Gamma-LpE (gamma-LpE), a sphingomyelin-rich lipoprotein that contains
      apolipoprotein (apo) E as its only protein component, has been proposed to play a
      role in cellular cholesterol efflux by acting, like pre-beta1-LpA-I, as an
      initial acceptor of cell-derived cholesterol. In order to further characterize
      the presence of gamma-LpE in human plasma, we have separated gamma-LpE by two
      dimensional non-denaturing polyacrylamide-gradient gel electrophoresis and
      detected its presence by immunoblotting with 125I-labeled polyclonal anti-apoE
      antibody. Five species of gamma-LpE were routinely detected in human plasma,
      ranging in mean particle diameter from 9.5 to 16.5 nm. The largest proportion of
      gamma-migrating apoE was associated with gamma-LpE having a diameter of 13.0 nm.
      Neither the amount of gamma-LpE apoE (representing less than 1-2% of total plasma
      apoE) nor the number of gamma-LpE subfractions was different in serum vs. plasma,
      or was affected by the presence of agents able to inhibit protein dimerization.
      Gamma-LpE subfractions were present in the plasma of patients having different
      apoE phenotypes (i.e., apoE 2/2, 3/3, or 4/4). Incubation of plasma at 37 degrees
      C (90 min) caused a significant decrease in plasma gamma-LpE (>80%) that was not
      dependent on LCAT or CETP activity. Storage (at -70 degrees C) of
      hypertriglyceridemic but not normolipidemic plasma resulted in an increase in
      gamma-LpE. Freezing of postprandial plasma samples, containing increased amounts
      of triglyceride-rich lipoproteins (TRL) enriched in apoE, also caused an increase
      in gamma-LpE. Incubation of VLDL (d < 1.006 g/ml) with lipase resulted in the
      production of gamma-migrating apoE. These results demonstrate that: 1) different
      gamma-LpE subfractions exist in human plasma; 2) the amount of apoE associated
      with gamma-LpE subfractions is dependent on in vitro conditions of plasma
      storage; and 3) TRL can act as a source of gamma-LpE apoE in vitro.

PMID- 9555950
TI  - Docosahexaenoic acid lowers phosphatidate level in human activated lymphocytes
      despite phospholipase D activation.
AB  - N-3 polyunsaturated fatty acids from marine oil have been shown to decrease T
      cell-mediated immune function both in animals and humans, and to inhibit the
      mitogen-induced lymphoproliferative response when added to lymphocyte culture
      medium. As phosphatidic acid (PA) is a key mediator of the mitogenic process, the
      present study aims to investigate whether docosahexaenoic (DHA) and
      eicosapentaenoic (EPA) acids, the main n-3 fatty acids from fish oil, are able to
      alter the mitogen-induced synthesis of PA, when added to the culture medium of
      human peripheral blood mononuclear cells (PBMC). Incubation of PBMC in a medium
      containing 5 microM DHA bound to 5 microM human delipidated serum albumin induced
      a 2-fold increase in the basal PA mass whereas incubation with EPA, in the same
      conditions, had no effect. In contrast, both fatty acids markedly reduced the
      concanavalin A (ConA)-induced production of PA as compared with untreated cells.
      Paradoxically, phospholipase D (PLD) activity, evidenced by the synthesis of
      phosphatidylbutanol, was only detected in DHA-treated cells further stimulated by
      ConA, indicating that both DHA and ConA are required for PLD activation.
      Similarly, an increased diacylglycerol (DAG) mass was only observed in DHA
      treated cells stimulated by ConA, whereas no modification occurred in control or
      EPA-treated cells stimulated or not by ConA. Furthermore, 1-butanol suppressed
      the ConA-induced increase of DAG mass observed in DHA-treated cells, indicating
      that phosphatidate was the source of the newly synthesized diacylglycerol.
      Altogether, these results show that, in concanavalin A-activated human peripheral
      blood mononuclear cells, docosahexaenoate stimulates both phospholipase D and
      phosphatidate phosphohydrolase activities, which ultimately results in an
      increased diacylglycerol production at the expense of phosphatidate.

PMID- 9555951
TI  - Coordinated release of acylation stimulating protein (ASP) and triacylglycerol
      clearance by human adipose tissue in vivo in the postprandial period.
AB  - The objective of this study was to determine whether Acylation Stimulating
      Protein (ASP) is generated in vivo by human adipose tissue during the
      postprandial period. After a fat meal, samples from 12 subjects were obtained (up
      to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that
      drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous
      adipose tissue bed were calculated. The data demonstrate that ASP is produced in
      vivo (positive V-A gradient) With maximal production at 3-5 h postprandially. The
      plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient.
      It increased substantially after 3 h and remained prominent until the final time
      point. There was, therefore, a close temporal coordination between ASP generation
      and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid
      (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into
      adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty
      acid (NEFA) differences postprandially. FIAT was negative during the first hour,
      implying net fat mobilization. FIAT then became increasingly positive, implying
      net fat deposition, and overall followed the same time course as ASP and TAG
      clearance. There was a direct positive correlation between total ASP production
      and total FIAT (r = 0.566, P < 0.05). These data demonstrate that ASP is
      generated in vivo by human adipocytes and that this process is accentuated
      postprandially, supporting the concept that ASP plays an important role in
      clearance of TAG from plasma and fatty acid storage in adipose tissue.

PMID- 9555952
TI  - Phytosterols partially explain differences in cholesterol metabolism caused by
      corn or olive oil feeding.
AB  - To examine whether phytosterols in polyunsaturated oils account for their
      differential action on lipid metabolism compared with monounsaturated oils, 16
      normolipidemic individuals consumed three 10-day experimental diets containing
      corn oil (high in polyunsaturated fatty acids and phytosterols), olive oil (high
      in monounsaturated fatty acids and low in phytosterols), or olive oil
      supplemented with phytosterols given at twice the level naturally found in corn
      oil (high in monounsaturated fatty acids and phytosterols). Plasma total
      cholesterol concentrations after both the olive oil and the olive oil-phytosterol
      treatments were higher (P < 0.001) than those after the corn oil treatment. Olive
      oil treatment resulted in greater (P < 0.05) plasma LDL-cholesterol and
      triglyceride concentrations compared to corn oil treatment. Addition of the
      phytosterol mixture to the olive oil diet resulted in suppression of the
      significant differences in LDL-cholesterol and triglyceride concentrations
      between corn and olive oil. Free cholesterol fractional synthetic rates
      determined by deuterium incorporation were lower (P < 0.05) with olive oil
      treatment compared to corn oil treatment; the significance of this difference was
      abolished with the addition of phytosterols to the olive oil diet. These results
      suggest that phytosterols are partly responsible for the differences in plasma
      cholesterol levels and synthesis observed between polyunsaturated and
      monounsaturated oils.

PMID- 9555953
TI  - Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin
      fibroblasts.
AB  - Consumption of boiled coffee promotes an elevation of plasma cholesterol
      concentration in humans. The active compounds found in the lipid fraction of the
      coffee have been identified as the diterpenes cafestol and kahweol. We have
      studied the effects of pure cafestol on cholesterol metabolism in human skin
      fibroblasts (HSF). The uptake of [125I]-labeled tyramine cellobiose-labeled low
      density lipoprotein ([125I]TC-LDL) was decreased by about 50% (P< 0.05) after 18
      h preincubation time with cafestol (20 microg/ml), as compared to the control
      cells. The specific binding of radiolabeled LDL was reduced by 54% (P < 0.05)
      after preincubation for 18 h with cafestol. A reduced amount of LDL receptors was
      demonstrated by a protein-normalized Scatchard plot analysis (20% decrease in
      Bmax) as well as by immunoblotting (25%) after cafestol incubation. No
      significant effect was observed on the level of mRNA for the LDL receptor after
      11 and 23 h incubation with cafestol. Furthermore, we transfected HSF cells with
      a promoter region for the LDL receptor gene linked to a reporter gene,
      chloramphenicol acetyl transferase (CAT). No change was seen in the CAT activity
      after incubation with cafestol (20 microg/ml). Moreover, cafestol caused a 2.3
      fold (P < 0.05) higher incorporation of radiolabeled [14C]oleic acid into
      cholesteryl esters after 24 h incubation, as compared to control cells,
      suggesting an increased acyl-CoA:cholesterol acyl transferase (ACAT) activity.
      Incorporation of [14C]acetate into cholesterol was reduced by approximately 40%
      (P < 0.05) with cafestol (20 microg/ml), as compared to control after 24 h
      preincubation, indicating a decreased 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
      reductase activity. Our results suggest that intake of cafestol may cause
      increased concentration of plasma cholesterol via the down-regulation of low
      density lipoprotein receptors by post-transcriptional mechanisms.

PMID- 9555954
TI  - Three-fold effect of lovastatin treatment on low density lipoprotein metabolism
      in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB
      production, and decrease in particle affinity for the receptor. Results from a
      novel triple-tracer approach.
AB  - To differentiate effects of lovastatin on low density lipoprotein (LDL) receptor
      activity from effects on LDL metabolic properties, LDL apolipoprotein B (apoB)
      turnover was studied in eight hyperlipidemic subjects during baseline and
      lovastatin treatment, in the latter case with LDL tracers isolated during both
      baseline (CLDL) and drug treatment (Rx-LDL) conditions. Lovastatin (40 mg/day)
      significantly lowered total plasma and LDL cholesterol levels (27% and 25%,
      respectively) as well as plasma triglyceride levels (30%). Using contemporaneous
      tracers (C-LDL before and Rx-LDL during treatment), lovastatin caused a modest
      increase in LDL fractional catabolic rate (FCR) (0.410+/-0.113 vs. 0.339+/-0.108
      pools/day, P < 0.04 by paired t). The increase in LDL tracer FCR was higher when
      C-LDL tracer isolated during the untreated period was injected during lovastatin
      treatment (0.496+/-0.177 vs. 0.339+/-0.108 pools/day, P < 0.02). These in vivo
      studies in humans were confirmed by injecting LDL tracers from two patients into
      five guinea pigs. The C-LDL tracer was cleared consistently faster than the Rx
      LDL tracer (0.082+/-0.018 vs. 0.057+/-0.015 pools/h, P< 0.001). The results
      demonstrate three important outcomes of lovastatin treatment in these subjects:
      LDL receptor activity increased by 49% (P < 0.02); LDL apoB production rate
      decreased by 17% (P < 0.03), and LDL particle in vivo affinity for the LDL
      receptor decreased by 15% (P < 0.01). The decrease in LDL particle affinity
      partially negated the expected effect of increased LDL receptors on LDL
      clearance. The present study provides an explanation for earlier observations by
      several investigators using contemporaneous tracers that treatment with HMG-CoA
      reductase inhibitors resulted in only modest increases in low density lipoprotein
      functional catabolic rate.

PMID- 9555955
TI  - Generation and initial characterization of a novel polyclonal antibody directed
      against homocysteine thiolactone-modified low density lipoprotein.
AB  - Elevated plasma homocysteine (homocysteinemia) are presumed to be responsible for
      the development of coronary artery disease, however, the precise etiology is
      unclear. We examined the possibility that the adduct formed from the reaction
      between homocysteine thiolactone, a metabolic product of homocysteine, and
      apolipoprotein B-100 lysyl residues of low density lipoprotein (LDL) was
      immunogenic. New Zealand White rabbits were immunized with this adduct at 6-week
      intervals. Antisera collected following the 3rd immunization was assayed for
      antibody titers using solid phase ELISA techniques. Titers (defined as the
      inverse of the greatest serum dilution in which there was a significant
      difference (P < 0.05) between the percentage antibody bound from the antiserum
      and the pre-immune serum) were approximately 10(5). In competition-based ELISAs,
      homocysteine thiolactone-treated LDL competed for binding with the antiserum, as
      the 50% inhibitory concentration was approximately 10 microg/ml. Neither
      homocysteine, homocystine (homocysteine disulfide), nor Cu2-oxidized LDL competed
      for binding. LDL in which lysyl residues were derivatized by acetylation or
      methylation were not recognized by the antiserum. Homocysteine thiolactone
      treated plasma competed for binding to the antiserum, whereas native plasma did
      not. All lipoprotein fractions from the homocysteine thiolactone-treated plasma
      competed for binding to the antiserum. We conclude that homocysteine thiolactone
      modified LDL is highly immunogenic and specific for homocysteine thiolactone
      modified lysines. The potential for using this antibody as a diagnostic tool for
      measuring plasma homocysteine concentrations and the implications for
      understanding diseases induced by homocysteinemia are discussed.

PMID- 9555956
TI  - Enhanced detection of lipoprotein lipase by combining immunoprecipitation with
      Western blot analysis.
AB  - This manuscript describes the problems inherent in combining immunoprecipitation
      of lipoprotein lipase (LPL) with its detection by Western blot, and how these
      problems can be circumvented by the preparation of suitable immunoreagents. These
      reagents used during the immunoprecipitation step, include Fab fragments of the
      primary antibody (chicken anti-bovine LPL), and a covalently linked immunomatrix
      of the secondary antibody (rabbit anti-chicken IgG). The use of these reagents in
      conjunction with Western blot detection virtually eliminates the problem of non
      relevant protein detection when analyzing LPL from complex biological samples.
      Moreover, this approach can be adapted to detect any protein with the same
      inherent problems as LPL, such as hepatic lipase.

PMID- 9555957
TI  - Don't kill Japanese hemodialysis patients like America kills its patients.

PMID- 9555958
TI  - A simple and early prognostic index for acute renal failure patients requiring
      renal replacement therapy.
AB  - Recent advances in technology have not substantially changed the high mortality
      rate associated with acute renal failure (ARF). To obtain a simple, valid
      prognostic index, we retrospectively evaluated the relative importance of
      demographic data, causes (acute insults) of renal failure, and comorbid clinical
      conditions for the outcome in 102 ARF patients who received renal replacement
      therapy with an overall mortality rate of 65% (66 of 102). There were no
      significant differences between survivors and nonsurvivors in age and gender.
      Mortality according to acute insults was similar to that of the whole population
      studied. Of the 10 clinical conditions at the time of the first renal replacement
      therapy, mechanical ventilation (p = 0.0002), cardiac failure (p = 0.0006),
      hepatic failure (p = 0.003), central nervous system dysfunction (p = 0.005), and
      oliguria (p = 0.04) were found to be significantly related to mortality by
      univariate analysis. Furthermore, multivariate analysis demonstrated that only
      mechanical ventilation, cardiac failure, and hepatic failure were significant
      risk factors. Survival was directly related to the number of significant
      variables in univariate analysis: zero, 89% (8 of 9); one, 62% (21 of 34); two,
      19% (5 of 27); three, 10% (2 of 20); four, 0% (0 of 8); five, 0% (0 of 4). This
      simple and early prognostic index, derived from the assessment of clinical
      conditions which were easily determined at the patient's bedside, could be useful
      for outcome prediction in ARF patients requiring renal replacement therapy.

PMID- 9555959
TI  - Centralized on-line hemodiafiltration system utilizing purified dialysate as
      substitution fluid.
AB  - We followed the guidelines of the Kyushu Society for Hemodiafiltration (HDF)
      Therapy on the purification of dialysate used as substitution fluid and
      clinically applied HDF using only 20 L or 15 L of substitution fluid in the pre-
      or postdilution mode, respectively. We used a centralized on-line HDF system
      consisting of a novel multi-patient dialysate delivery system applying 3
      endotoxin (ET) removal filters in series, maintaining the ET level within the
      criteria limit below 1.0 IU/L (measured at the first filter outlet to be 0.1 IU/L
      and after the third filter to be below the sensitivity limit) irrespective of the
      fluctuation in the ET level of the tap water. Low molecular weight proteins
      (beta2-microglobulin, prolactin, alpha1-microglobulin, and alpha1-acid
      glycoprotein) were more effectively removed in this HDF system than in
      conventional hemodialysis (HD) using the same dialyzer as that in the HDF system,
      and the removal of these proteins in the HDF system was enhanced as their
      molecular weights increased. The clinical effect of the HDF system was
      demonstrated by a decrease in joint pain accompanied by improvement in joint
      motion in 6 dialysis patients followed over the long term (100 weeks).

PMID- 9555960
TI  - Glucose-insulin kinetics of a bioartificial pancreas made of an AN69 hydrogel
      hollow fiber containing porcine islets and implanted in diabetic mice.
AB  - The goal of this study was to determine whether porcine islets encapsulated in
      hollow fibers made of AN69 copolymer can correct hyperglycemia in diabetic mice
      and provide normal tolerance to a glucose challenge. In vitro perifusion of
      hollow fibers demonstrated the rapid kinetics of insulin release in response to
      glucose. Two fibers containing islets were transplanted into the peritoneal
      cavity of each of 17 streptozotocin induced diabetic mice. In 11 mice, diabetes
      was reversed within 3 days with plasma glucose levels decreasing from 19.7 +/-
      0.9 (mean +/- SEM) before implantation to 10.9 +/- 0.8 mmol/L. Intraperitoneal
      glucose tolerance tests were performed in transplanted (n = 7), nondiabetic (n =
      15), and diabetic mice (n = 6). A normal glucose pattern was observed in the
      transplanted diabetic mice. This was achieved in the presence of plasma insulin
      levels lower than those observed in control nondiabetic mice, suggesting the
      presence of a state of hypersensitivity to insulin, which was demonstrated in
      this model by exogenous insulin tolerance tests. In conclusion, encapsulation of
      islets suspended in ultraculture medium in biocompatible membranes of AN69 can
      provide xenograft survival, and complete normalization of glucose tolerance can
      be achieved.

PMID- 9555961
TI  - Effect of high concentrations of bile acids on cultured hepatocytes.
AB  - High concentrations of bile acids have been reported as injurious to hepatocytes.
      We report the influence of various combinations of bile acids on the liver
      specific function of cultured rat hepatocytes. Using 4 bile acids (glycocholate
      [GC], taurocholate [TC], glycohenodeoxycholate [GCDC], and taurochenodeoxycholate
      [TCDC]), we obtained 6 bile-acid mixtures, each containing equal amounts of 2
      bile acids (total bile acids [TBA], 2 mM). Changes in gluconeogenesis,
      ureagenesis, DNA contents, medium alanine aminotransferase, and morphologies were
      compared among the paired bile acid compositions by measuring the C/CDC ratio
      ([GC + TC]/[GCDC + TCDC]) of each. In terms of their relative impairments of
      ureagenesis from greatest to least, the acids were GCDC, TCDC, and GC, which was
      almost the same as TC. When the C/CDC ratio was 0, the values of all parameters
      measured deteriorated. When the C/CDC ratio was 1 in the presence of 1 mM GCDC,
      only the rate of ureagenesis was diminished. When the C/CDC ratio was infinite,
      no hepatocellular injury was observed. GCDC and TCDC, together or separately,
      showed significant hepatocellular injury when the TBA concentration was 2 mM.

PMID- 9555962
TI  - Comparison of three solid phase supports for promoting three-dimensional growth
      and function of human liver cell lines.
AB  - An extracorporeal liver support system will require that liver cells maintain
      their normal differentiated function. This is more likely to be achieved
      utilizing a three-dimensional culture configuration rather than a simple
      monolayer culture. We present data on a human liver cell line attached and
      maintained on different three-dimensional supports, porous glass (Siran), silicon
      (Immobasil), and calcium-alginate beads. Albumin, fibrinogen, prothrombin, alpha1
      acid glycoprotein and alpha1-antitrypsin secretions were measured. Proliferation
      was slower on each of the three-dimensional supports than on the monolayer
      culture. The protein secretion of all 5 proteins was highest in cells
      encapsulated in alginate; silicon beads supported greater protein secretion than
      glass. Cells on silicon or within alginate were rounded; those on glass grew in 2
      configurations as flattened monolayers and as rounded colonies. Cells in alginate
      secreted as much protein as the whole liver (e.g., albumin, 14.88 g/10(12)
      cells/day compared to the whole liver, approximately 12 g/day). Three-dimensional
      culture of a human liver cell line leads to both proliferation and a high
      synthetic capacity, an important feature of cells suitable for an extracorporeal
      liver support system.

PMID- 9555964
TI  - Centrifugal pumping during routine open heart surgery improves clinical outcome.
AB  - Carrying out a 1,000 patient prospective, randomized study comparing a roller
      pump and the BioMedicus centrifugal pump (CP), hematological parameters, blood
      loss, renal function, postoperative complications, and lethality data were
      evaluated. Using a validated preoperative risk stratification method (Cardiac
      RiskMaster), patients were divided into different risk categories for statistical
      analysis. This study verified an improved outcome with the use of a CP in routine
      cardiac surgery, demonstrated by blood handling, blood loss, renal function, and
      nephrological complication data. There was also a significant reduction in
      neurological complications. There was no significant difference in postoperative
      lethality, but high risk patients demonstrated outcomes comparable to those being
      defined for medium risk patients. Routine cardiac surgical patients as well as
      multimorbid patients benefit from the use of a CP. Preoperative risk
      stratification is a valid tool to demonstrate how the employment of new
      technologies can provide for an improved outcome without increasing overall costs
      at the same time.

PMID- 9555963
TI  - Coronary vascular bed perfusion with a polyethylene glycol-modified hemoglobin
      encapsulated liposome, neo red cell, in rats.
AB  - Whether hemoglobin (Hb) encapsulated liposomes have vasoconstrictive activity
      remains controversial. We therefore examined the vascular activity of a liposome
      Hb, Neo red cell (NRC), in a simple in vitro model of Langendorff perfusion of
      the rat heart using Krebs-Henseleit (KH) solution as the perfusate. In the KH
      solution, NRC (Hb at 1 mg/ml), however, induced an immediate and abnormal
      increase in perfusion pressure. Histological examinations revealed that embolisms
      were the likely cause of this disturbance. Inorganic crystals formed by the
      mixing of NRC with the perfusate were a possible source of the embolisms. We
      found that the addition of bovine serum albumin to the perfusate was effective in
      avoiding embolic events. This protocol was used to compare the vasoconstrictive
      properties of unmodified bovine Hb and NRC. Unmodified bovine Hb (1 mg/ml) caused
      an increase in perfusion pressure and a decrease in the duration of bradykinin
      induced relaxation. In contrast, NRC (Hb at 1 mg/ml) had no such vasoconstrictive
      effects. These results provide the first information regarding perfusion of the
      circulatory vascular bed by NRC and further evidence that the encapsulation of Hb
      into liposomes is an effective approach to modulate Hb-related vasoconstrictive
      activity.

PMID- 9555966
TI  - The safety system for the rotary blood pump, combination of the valve and LVAD
      pulsatile mode: in vitro test.
AB  - The significant amount of regurgitation produced by a stopped rotary blood pump
      is one of the major considerations for its use as an implantable left ventricular
      assist device (LVAD), especially if the pump accidentally stops. The installation
      of a valve is an option for the solution of this potential problem. However, this
      option may lead to thrombogenic problems, particularly if the valve motion is
      restricted. This in vitro study analyzes the valve performance and assesses the
      credibility of a rotary blood pump valve. A pulsatile pump was used as the
      natural heart and a centrifugal pump as the LVAD. The valve was positioned into
      the LVAD outflow. In the low speed range (<1,000 rpm in this test condition),
      normal valve motion was maintained. Also, the valve model provided a higher mean
      bypass flow than the model without a valve due to reduced regurgitation. However,
      the valve motion was drastically restricted when in the high speed range (>1,600
      rpm in this condition). The pulsatile mode was applied to the LVAD by
      periodically changing the impeller speed (40 bpm); subsequently, a constant valve
      motion could be provided. A possibility exists that this pulsatile mode
      application could eliminate thrombosis formation around the valve. A conclusion
      was made that the combination of a valve and an LVAD in a pulsatile mode is
      considered to be a unique safety system for a rotary blood pump.

PMID- 9555967
TI  - New bedside test for monitoring anticoagulation during hemodialysis.
AB  - Heparin therapy in patients can be monitored bedside during dialysis treatment by
      activated partial thromboplastin time (APTT) measurements using portable
      coagulation monitors. We verified the efficacy of the CoaguChek Plus System
      (Boehringer Mannheim, GmbH, Mannheim, Germany) for this purpose. The first series
      of results was obtained using CoaguChek Plus APTT controls (Level 1 and Level 2)
      on 3 instruments. The coefficients of variation (CVs) were found to be in the
      range of 3.6 to 5.0% based on results per instrument (n = 20) and per control
      level (n = 60). The second series of results was obtained using whole blood drawn
      from the arterial lines of patients during dialysis treatment. Three
      determinations out of 1 ml of fresh whole blood gave an overall mean CV of 4.9%
      from the 123 samples tested. Samples were taken before the onset of heparin
      treatment, 2 h after treatment was started, and at the end of treatment. The
      CoaguChek Plus APTT measurements were compared to measurements made using
      laboratory routine method STA APTT (Boehringer Mannheim GmbH) with results from
      104 whole blood samples. Regression analysis according to Passing and Bablok
      showed good correlation (r = 0.885) and good agreement (y = 0.997x - 6.6) between
      both methods. Ease of use, excellent performance, reliability, and rapid
      availability of results within 3 min make the CoaguChek Plus APTT measurements
      suitable for monitoring patients during dialysis.

PMID- 9555965
TI  - A novel technique for cardiopulmonary bypass using vacuum system for venous
      drainage with pressure relief valve: an experimental study.
AB  - To decrease the circuit priming volume, develop safety, and simplify the
      equipment, a cardiopulmonary bypass (CPB) circuit using a vacuum suction venous
      drainage system with a pressure relief valve was developed. The efficacy of this
      vacuum system was compared to that of a conventional siphon system. The system
      contains a powerful vacuum generator and a pressure relief valve to keep the
      negative pressure constant when blood suction is used. Using 8 mongrel dogs, the
      feasibility and the efficacy of this CPB system was tested. The changes in the
      negative pressure in the reservoir were within 5 mm Hg whether the suction lines
      were switched on or off. In all animals the amount of blood in the venous
      reservoir was stable throughout bypass. The decrease of priming volume was from
      725 ml (siphon system) to 250 ml (vacuum system). At the end of CPB, the levels
      of hemoglobin in the vacuum system were significantly higher than those in the
      siphon system. These results demonstrated that this vacuum drainage system can
      provide simplification and a miniaturization of the cardiopulmonary bypass
      circuit resulting in low hemodilution during CPB.

PMID- 9555968
TI  - Platelet protective effect of TAK-029, a novel glycoprotein IIb/IIIa antagonist:
      an in vitro study.
AB  - Previous studies have indicated that exposure of fibrinogen receptors associated
      with the glycoprotein IIb/IIIa complex contributes to platelet loss during
      cardiopulmonary bypass. TAK-029 is a newly developed reversible, nonpeptide
      inhibitor of platelet glycoprotein IIb/IIIa receptors. In this study, we tested
      the platelet preserving effect of TAK-029 in an in vitro model. The methods
      included the comparison of the release of beta-thromboglobulin (beta-TG) between
      a TAK-029 group (n = 5) and a control group (n = 5) in a mock circulation under a
      shear force generated by a centrifugal pump. To evaluate the degree of beta-TG
      release, deltabeta-TG/deltaT was calculated where deltabeta-TG is the increase in
      beta-TG and deltaT is the time. The results showed that the value of deltabeta
      TG/deltaT in the TAK-029 group was significantly lower than it was in the control
      group (4.22 +/- 0.27 x 10(2) ng/ml vs. 7.33 +/- 0.66 x 10(2) ng/ml,
      respectively). In conclusion, TAK-029 reduced the platelet activation under the
      shear forces of an in vitro model, suggesting that TAK-029 is a potential
      candidate for platelet protection during cardiopulmonary bypass.

PMID- 9555969
TI  - Rivastigmine, a brain-selective acetylcholinesterase inhibitor, ameliorates
      cognitive and motor deficits induced by closed-head injury in the mouse.
AB  - The effects of Rivastigmine, a novel centrally-acting anticholinesterase agent,
      were evaluated on cerebral edema, neurological and motor deficits, and impairment
      of spatial memory induced in mice by closed-head injury (CHI). Severe injury was
      induced in the left hemisphere of mice under ether anesthesia. Rivastigmine (1 or
      2 mg/kg) or saline (10 ml/kg) was injected SC 5 min later. Rivastigmine (2 mg/kg)
      reduced cerebral edema by at least 50% (p < 0.01), 24 h after CHI and accelerated
      the recovery of motor function 7 and 14 days after CHI. Control mice (n = 24),
      previously trained to find the goal platform in a Morris water maze failed to
      recall or relearn its position for at least 11 days post-injury. Those given a
      single injection of Rivastigmine (2 mg/kg) regained their pre-test latencies by
      the third day after CHI. The neuroprotective effects of Rivastigmine on brain
      edema, neurological and motor function, and performance in the Morris water maze
      were completely antagonized by simultaneous SC injection of either scopolamine
      (0.5 mg/kg) or mecamylamine (2.5 mg/kg). The antagonists alone had no significant
      effect on any of these parameters. These data show that the reduction by
      Rivastigmine of the immediate and long-term sequelae of brain injury are mediated
      by increased cholinergic activity at both muscarinic and nicotinic receptors.

PMID- 9555970
TI  - Neurological recovery in diabetic rats following spinal cord injury.
AB  - This study was designed to assess the effect of spinal cord injury on
      neurobehavioral, electrophysiological, structural, and biochemical changes in
      normal and diabetic rats. Experimental diabetes was induced in Sprague-Dawley
      male rats (weighing 250-280 g) with streptozotocin (50 mg/kg i.p.). Eight weeks
      after the treatment with streptozotocin the animals were anaesthetized with
      chloral hydrate and laminectomy was performed at T 7-8 level leaving the dura
      intact. A compression plate (2.2 x 5.0 mm) loaded with a weight of 35 g was
      placed on the exposed spinal cord for 5 min. Postoperative neurological function
      was assessed using inclined plane test, modified Tarlov score, and vocal and
      sensory score daily for 10 days. Electrophysiological changes were assessed using
      somatosensory and corticomotor evoked-potentials. The animals were sacrificed at
      different time intervals and injured site of the spinal cord was analyzed for
      changes in vitamin E and glutathione levels (as markers of oxidative stress).
      Pathological changes in spinal cord were also studied using light microscopy. The
      data on neurobehavioral study clearly indicated that the compression of spinal
      cord produced highly significant neurological deficit and poor recovery in
      diabetic rats as compared to nondiabetic rats. Our histopathological and
      electrophysiological results also confirmed that diabetic animals are more
      susceptible to compressive spinal cord injury as compared to nondiabetic animals.
      A higher depletion of antioxidant defense markers (vitamin E and glutathione) was
      observed in diabetic rats as compared to nondiabetic rats. These results point
      toward the role of free radicals in poor recovery in diabetic rats following
      neurotrauma. Further studies are warranted to assess the neuroprotective
      potential of antioxidants to retard the secondary pathophysiological events
      following neurotrauma and to enhance the recovery.

PMID- 9555971
TI  - Clinical significance of CSF glutamate concentrations following severe traumatic
      brain injury in humans.
AB  - Glutamate excitotoxicity is a putative mechanism of secondary damage after
      traumatic brain injury (TBI). No relationship between glutamate release and
      clinical status has been shown in humans, however. We hypothesize a dose-response
      relationship between CSF glutamate concentrations and severity of injury,
      electrophysiological deterioration as measured by somatosensory evoked potential
      amplitudes, and clinical outcome. From August 1991 to March 1996, intensive
      monitoring of 55 patients with severe TBI (GCS < or = 8 after resuscitation)
      included twice daily CSF glutamate levels and hourly somatosensory evoked
      potentials (SSEPs) for an average of 5 days. Clinical outcomes were
      survival/nonsurvival and Glasgow outcome score (GOS) at 3 months or more post
      injury. Glutamate levels were not associated with severity of injury,
      electrophysiological deterioration, or clinical outcome. Neither peak nor mean
      glutamate levels significantly improved a simple logistic regression model which
      used only age and presence of bilaterally unreactive pupils to predict survival.
      Using this methodology CSF glutamate concentrations did not display a dose
      response relationship to severity of injury, electrophysiological deterioration,
      or predict clinical outcomes following TBI in a group of 55 patients. An early
      effect of glutamate, an effect dependent on time of exposure to glutamate or
      other modulating effects cannot be ruled out.

PMID- 9555972
TI  - Comparison between continuous brain tissue pO2, pCO2, pH, and temperature and
      simultaneous cerebrovenous measurement using a multisensor probe in a porcine
      intracranial pressure model.
AB  - Local brain tissue oxygenation (p(ti)O2) and global cerebrovenous hemoglobin
      saturation (SjO2) are increasingly used to continuously monitor patients after
      severe head injury (SHI). In patients, simultaneous local and global oxygen
      measurements of these types have shown different results regarding the
      comparability of the findings during changes in CPP and ICP. This is in contrast
      to theoretical expectations. The aim of this study was to compare p(ti)O2
      measurement with cerebrovenous oxygen partial pressure measurement (p(cv)O2) in
      an animal intracranial pressure model. To this end, a multisensor probe was
      placed in the left frontoparietal white matter to measure p(ti)O2, pCO2
      (p(ti)CO2), pH (pH[ti]), and temperature (t[ti]) while simultaneously measuring
      these same parameters (p(cv)O2, p(cv)CO2 pH(cv), t[cv]) in the sagittal sinus of
      9 pigs under general anesthesia. By stepwise inflating a balloon catheter, placed
      in supracerebellar infratentorial compartment, ICP was increased and CPP was
      decreased. The baseline levels of p(ti)O2, p(ti)CO2, and pH(ti) in the noninjured
      brain tissue showed more heterogeneity compared to the findings in cerebrovenous
      blood. Both, p(ti)O2 and p(cv)O2 were significantly correlated to the induced CPP
      decrease. PCO2 was inversely correlated to the course of CPP in both measurement
      compartments. Temperature measurement showed a positive correlation with CPP in
      both compartments. These findings demonstrate that brain tissue oximetry and
      cerebrovenous PO2 measurement are sensitive to CPP changes. The newly available
      continuous parameters in multisensor probes could be helpful in interpreting
      findings of cerebral oxygen measurement in man by analyzing the interrelationship
      of these parameters.

PMID- 9555973
TI  - Spreading depression induces depletion of MAP2 in area CA3 of the hippocampus in
      a rat unilateral carotid artery occlusion model.
AB  - Traumatic brain injury (TBI) induces neuronal cell loss in area CA3 of the
      hippocampus. However, it has not yet been established why traumatic injury of the
      cortex induces neuronal damage in more remote areas. Spreading depression (SD)
      may be one potential mechanism for this pathophysiology. The present study
      evaluated whether SD on the cortex evokes a pathological change in the
      hippocampus. Forty-two Fisher rats were assigned to four groups: Group I: sham
      operation (n = 7), Group II: right carotid occlusion (UO) for 7 days (n = 7),
      Group III: repeated induction of SD by KCl application on dura for 7 days (n =
      7), Group III' for 3 h (n = 7), Group IV: SD induction and UO for 7 days (n = 14)
      Group IV' for 3 h (n = 7). In 5 out of 7 animals in Groups III' and IV', cerebral
      blood flow (CBF) was monitored using laser Doppler flowmetry for 3 h during the
      passage of SD. The brains were processed for immunohistochemical analysis of
      microtubule-associated protein 2 (MAP2). Reactive hyperemia induced by SD was not
      significantly suppressed by right carotid occlusion (194 +/- 25% and 181 +/- 42%
      UO in Groups III and IV, respectively). In 6 out of 7 animals in a 7-day model of
      Group IV, and 3 animals in a 7-day model of Group III, MAP2 depletion in the CA3
      area of the hippocampus (partly including CA2) was observed, although no change
      in the hippocampus was observed in other groups. In conclusion, SD in combination
      with UO yielded reproducible lesions in CA3. Neuronal injury in the hippocampus
      after brain trauma may be attributable to SD in combination with the blood flow
      restriction.

PMID- 9555974
TI  - Changes of amino acid levels and aspartate distribution in the cervical spinal
      cord after traumatic spinal cord injury.
AB  - To evaluate the role of excitatory amino acids in secondary injury occurring
      after spinal cord trauma, several experimental studies focusing on the the
      changes of amino acid levels in the spinal cord have been performed to date.
      However, because of technical limitations, it has not been possible to correlate
      the local changes of excitatory amino acids with the total tissue levels of
      excitatory amino acids. To investigate the connection between the spread of
      injury and the excitatory amino acids, we assessed, the local changes of
      aspartate through novel experimental approaches like immunoreactivity via
      fluorescence microphotometry and histopathology while also analyzing the total
      tissue levels of amino acids via HPLC. These studies were performed using a model
      of incomplete cervical spinal cord injury in rats. Through this approach, we
      found that the levels of excitatory amino acids, such as glutamate and aspartate,
      began to decrease immediately after injury. No significant decrease was observed
      in the other amino acids. Similarly, local changes in aspartate in the spinal
      cord were observed using fluorescence microphotometry. The decrease in the
      anterior and posterior horns was rapid up to 15 min after injury, but, slowed
      thereafter, suggesting that a release of excitatory amino acids occurred at the
      site of primary injury almost immediately following injury. At 15-min post-injury
      large neurons within the injured cord appeared intact on histopathological
      analysis demonstrating that the alteration of excitatory amino acids occurs prior
      to histopathological change. Histopathological change in the white matter
      occurred more slowly than in the anterior and posterior horns, suggesting the
      spread of the lesion by secondary damage due to an autoclastic mechanism.

PMID- 9555975
TI  - The role of IL-10 in iNOS and cytokine mRNA expression during in vitro
      differentiation of bovine mononuclear phagocytes.
AB  - In the study reported here, we used RT-PCR with primers specific for interleukin
      1 (IL-1), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide
      synthase (iNOS) to assess the cytokine mRNA expression associated with bovine
      blood monocytes during their differentiation to macrophages cultured on plastic
      (1 week). In addition, we used RT-PCR to assess the contribution of gammadelta T
      cells as a source of interferon-gamma (IFN-gamma), the induction signal for iNOS.
      Further, we evaluated cytocentrifuge preparations from the cultures for the
      production of IL-10 using specific antibody. We previously demonstrated that iNOS
      can be induced in cultured bovine monocytes in response to IFN-gamma and TNF
      alpha but lose this capability in a short period of time. However, we demonstrate
      here that iNOS induction from monocytes cultured with IFN-gamma secreting
      gammadelta T cells is prolonged, suggesting that this source of IFN-gamma primes
      the monocytes before exogenous stimulation. Based on mRNA expression, placement
      of monocytes in culture resulted in activation, followed by quiescence. By 6 days
      in culture, the iNOS message was reduced below the basal level. In addition, the
      TNF-alpha message was substantially reduced, and IL-1 and IL-6 messages were
      reduced below detectable levels. This correlated with an increase in IL-10
      message. Downregulation of these same cytokine messages as well as IFN-gamma
      message occurred within a 20-h period when IL-10 was added exogenously to
      cultures of total leukocytes. At the same time, there was an increase in the
      number of IL-10-positive cells and an increase in the intensity of anti-IL-10
      staining within adherent cells. These results provide evidence for IL-10
      regulation of some bovine mononuclear phagocyte effector functions.

PMID- 9555976
TI  - Immunization with HSV-1 antigen rapidly protects against HSV-1-induced
      encephalitis and is IFN-gamma independent.
AB  - Herpes simplex virus type 1 (HSV-1) infection of mice frequently culminates in
      fatal encephalitis. Intraperitoneal administration of heat-inactivated HSV-1 0-5
      days before infection (active immunization) protected mice from encephalitis. In
      addition, active immunization 2-5 days before ocular infection with HSV-1 reduced
      the frequency of establishment of latent HSV-1 infection in the trigeminal
      ganglion (TG). However, intraperitoneal administration of heat-inactivated HSV-1
      did not induce interferon (IFN) production in the peritoneum or serum, as
      determined by bioassay and ELISA. Intraperitoneal administration of heat
      attenuated HSV-1 elicited IFN-gamma but not type I IFN production in the
      peritoneum. The production of IFN-gamma correlated with the infiltration of CD4
      and CD8 cells in the peritoneum as determined by RT-PCR. In addition, there was a
      significant increase in interleukin (IL)-12 p40, IL-12p35, IL-6, IL-10, and IFN
      gamma mRNA in peritoneal cells, as determined by RT-PCR following immunization
      with heat-attenuated HSV-1, which was not observed using heat-inactivated HSV-1.
      The results suggest that resistance to HSV-1 is induced rapidly following
      immunization with viral antigen but that protection against encephalitis is
      independent of the cytokines that are generated in the peritoneum.

PMID- 9555978
TI  - Endothelial cell contact potentiates release of soluble tumor necrosis factor
      (TNF) receptors from the monocyte-like cell line THP-1.
AB  - The two tumor necrosis factor (TNF) receptors can undergo proteolytic cleavage to
      form soluble receptors, TNF-R55-BP and TNF-R75-BP, that can neutralize TNF. The
      aim was to study the release of soluble TNF receptor forms during monocyte
      endothelial cell interaction. Monocytic THP-1 cells were used, and their release
      of TNF-R75-BP was determined. Contact between THP-1 cells and confluent
      endothelial cells induced fourfold higher release of TNF-R75-BP from the THP-1
      cells than with these cells in suspension. The release was further increased up
      to eightfold after prestimulation of the endothelial cells with interleukin-1beta
      (IL-1beta). Prestimulation for 10 min gave maximal release of TNF-R75-BP from the
      attached THP-1 cells. IL-1beta by itself did not induce shedding of soluble TNF
      receptors in THP-1 cells. Blocking antibodies against the endothelial cell
      adhesion molecules VCAM, ICAM, and E-selectin did not affect the release of TNF
      R75-BP from THP-1 cells attached to the endothelium. Conditioned medium from IL
      1beta-stimulated endothelial cells increased the production of TNF-R75-BP from
      THP-1 cells in suspension. However, surface contact between endothelial cells and
      THP-1 cells was necessary for maximal production of TNF-R75-BP. TNF-alpha
      released from endothelial cells on IL-1beta stimulation did not promote shedding
      of TNF-R75 from THP-1 cells. Thus, endothelial cell contact potentiates the
      production of TNF-R75-BP in a monocyte-like cell line. The shedding of soluble
      TNF receptors observed in this case seems to be a result of both cell attachment
      and soluble factors.

PMID- 9555977
TI  - The comparative anti-herpes simplex virus effects of human interferons.
AB  - The mechanism(s) of anti-herpes simplex virus (HSV) activity of interferons
      (IFNs) have not been clearly identified. We have tested natural and recombinant
      human IFN-alpha, IFN-beta, and IFN-gamma preparations for their relative anti-HSV
      activity in human corneal and Vero monkey kidney cells. The relative anti-HSV
      activities in corneal cells were IFN-beta > rIFN-gamma > IFN-alpha
      (lymphoblastoid) > rIFN-beta2a = rIFN-alphaA/D. IFN-beta at 100 IU/ml reduced
      virus yield by 59+/-24%. The relative anti-HSV activity in Vero cells was rIFN
      gamma > IFN-beta = IFN-alpha (lymphoblastoid) > rIFN-alphaA/D > rIFN-alpha2a. IFN
      gamma at 100 IU/ml reduced virus yields by 90+/-4%. Reducing the multiplicity of
      infection significantly increased the apparent antiviral activity of all IFNs.
      The antiviral activity of IFNs could be detected by 4 h after treatment of Vero
      cells but not until 8 h in corneal cells. Western blot analysis showed that none
      of the IFNs detectably reduced the levels of immediate-early HSV protein, ICP4,
      but some reduced ICP0 levels early during infection, the extent and duration of
      the reduction varying with both IFN and cell type. The greatest effects on viral
      protein levels were detected in IFN-y-treated Vero cells. These data indicated
      that the targets of the anti-HSV activities of IFNs can vary with both IFN and
      cell type.

PMID- 9555979
TI  - Pretreatment with IFN-gamma decreases infectious complications after partial
      hepatectomy in the rat.
AB  - Infectious postoperative complications occur commonly after hepatectomy and may
      lead to a long hospital stay or death. The potential beneficial effects of
      interferon-gamma (IFN-gamma) in this setting were evaluated in a model of
      hepatectomy and sepsis in rodents. Incidence of bacterial translocation was
      measured in animals on days 1, 2, and 5 after partial hepatectomy. Macrophage
      function was quantified by in vitro tumoricidal activity and superoxide anion (O2
      ) production. Survival after partial hepatectomy and cecal ligation and puncture
      (CLP) was recorded. After partial hepatectomy, bacterial translocation was
      decreased on days 1 and 2 in animals pretreated with IFN-gamma (p < 0.05).
      Macrophages from animals treated with IFN-gamma had higher in vitro tumoricidal
      activity and production of O2- (p < 0.05). Hepatectomized animals pretreated with
      IFN-gamma had an increased survival after CLP (p < 0.05). IFN-gamma may be useful
      in decreasing the incidence of infectious complications after partial
      hepatectomy.

PMID- 9555980
TI  - Production of immunoreactive 2',5'-oligoadenylate synthetase in p48-deficient
      mice.
AB  - 2',5'-Oligoadenylate synthetase (2'5'OAS), an enzyme induced by interferon (IFN),
      is physiologically produced in IFN-untreated normal healthy mice. The enzyme is
      localized mainly in the epithelium of the digestive tract, reproductive organs,
      and the choroid plexus in the brain. 2'5'OAS is also detected in oocytes in the
      ovary and in neurons and glial cells of both the telencephalon and cerebellum.
      Here, we examined the role of p48 (ISGF3gamma), a component of IFN-stimulated
      gene factor 3 (ISGF3), in the physiologic production of 2'5'OAS using p48
      deficient mice generated by gene targeting. In the p48-deficient mice, the
      physiologic production of 2'5'OAS localized in the following cells was severely
      impaired: hepatocytes, Kupffer cells, splenocytes, epithelium of the large
      intestine, oviduct, and uterus, and neurons and glial cells in both the
      telencephalon and cerebellum. The results show that 2'5'OAS in these cells is
      induced physiologically through a pathway including p48. However, the production
      of 2'5'OAS in oocytes was not affected in the p48-deficient mice, indicating that
      oocyte 2'5'OAS is produced through a p48-independent pathway. A possible function
      of the GAS sequence found in the promoter region of the 2'5'OAS gene to which
      Stat6 may bind also is discussed.

PMID- 9555981
TI  - Interferon-induced expression of If-1h and If-1l alleles in Newcastle disease
      virus-infected mouse macrophages is associated with specific differences in viral
      gene transcription.
AB  - We have studied the expression of cytokines and viral genes induced by Newcastle
      disease virus (NDV) and Sendai virus in bone marrow-derived macrophages (BMM) and
      lymphocytes from C57BL/6 mice and the congenic line B6.C-H-28c. These mice carry
      the loci If-1h (high) or If-1l (low), respectively, that are responsible for up
      to tenfold differences in the interferon (IFN)-alpha, IFN-beta, interleukin-6 (IL
      6), and tumor necrosis factor-alpha (TNF-alpha) response to NDV but not to Sendai
      virus. Only BMM but not spleen lymphocytes showed allele-specific differences in
      NDV-induced cytokine levels, indicating cell-specific If-1 expression. The If-1
      locus harbors IFN-inducible gene(s) whose expression is prevented in the presence
      of cycloheximide. Our data provide evidence that the If-1l allele acts by
      specifically suppressing the cytokine response to NDV. Cytokine production was
      dependent on infectious virions, and kinetic analyses revealed a close
      correlation between the amount of viral transcripts and individual cytokine mRNA.
      BMM from lf-1l mice strongly restricted transcription of the NDV nucleoprotein
      (NP) gene, whereas BMM from If-1h mice supported NP transcription. Following
      treatment with IL-4, which inhibited constitutive IFN-beta gene expression,
      however, If-1l BMM became highly permissive for transcription of the viral NP
      gene and released high amounts of cytokines. We conclude that If-1l gene products
      are responsible for the low producer phenotype by efficiently interfering with
      NDV transcription, leading to strongly reduced intracellular levels of cytokine
      inducing viral dsRNA intermediates.

PMID- 9555982
TI  - IFN-gamma induces calcium transients and increases the capacitative calcium entry
      in human neutrophils.
AB  - We have previously reported that long-term priming of human polymorphonuclear
      neutrophilic granulocytes (PMN) with interferon-gamma (IFN-gamma) increased the
      fMLP-stimulated calcium influx. We now show that also after short-term incubation
      with IFN-gamma, PMN calcium metabolism is modulated. Single adherent cells in
      three different calcium-containing buffers (high, normal, and low [Ca2+]) were
      stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor
      thapsigargin (Tg) after about 5 min preincubation with IFN-gamma. The results of
      this protocol indicated that IFN-gamma increases both calcium influx and calcium
      sequestration. Store dependent Ca2+ influx, directly measured on readdition of
      calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced
      in IFN-gamma-treated cells. This effect of IFN-gamma was enhanced by the tyrosine
      kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium
      concentrations, IFN-gamma induced calcium transients in 20%-60% of the cells. The
      proportion of PMN responding with Ca2+ transients increased with decreasing
      extracellular calcium concentration. Average lagtime from addition of IFN-gamma
      to a response that could be measured was 7.3 sec, and average increase in [Ca2+]
      above the basal level was 790 nM. These IFN-gamma-induced transients could not be
      depressed by herbimycin A. Thus, IFN-gamma can increase capacitative calcium
      influx, induce calcium transients, and possibly affect calcium sequestration in
      human PMN.

PMID- 9555983
TI  - Dynamic cleft maxillary orthopedics and periosteoplasty: benefit or detriment?
AB  - In 1990, Drs Millard and Latham published their initial experience with dynamic
      maxillary appliances (DMAs) and periosteoplasty for children with cleft lip and
      palate. The technique provided for alveolar alignment and consolidation, with
      elimination of oronasal fistulas. Opponents to this approach speculated about
      impairments to facial growth. To date no longitudinal studies have been
      published. Over the last 10 years, 35 unilateral and 10 bilateral complete clefts
      have been treated with this technique. All patients have been followed and
      documented clinically, orthodontically, and radiographically. Cephalometric
      analyses were performed on children after the age of 6 years. The children have
      excellent facial aesthetics with well-balanced lips and noses. Radiographs
      demonstrate bone within the repaired alveolar clefts. Articulated impressions
      show anterior and lateral crossbites in the unilateral patients that improve over
      time and appear to be correctable orthodontically. The bilateral patients have
      satisfactory occlusions and arch forms. Cephalometric analyses confirmed no
      evidence of skeletal crossbites or midfacial growth retardation. This is a work
      in progress that will continue as the children grow. Although definite and final
      conclusions would be premature, it can be stated that to date all patients are
      following consistent and favorable growth patterns. Our team is confident in
      proceeding with this technique.

PMID- 9555984
TI  - Erbium:YAG laser skin resurfacing: preliminary clinical evaluation.
AB  - Each of the increasing number of resurfacing lasers uses a unique strategy to
      produce tissue ablation. Erbium:YAG (Er:YAG) lasers have been used in other
      applications for precise tissue removal with little thermal effect. Recovery
      time, duration of erythema, and clinical improvement were evaluated using an
      Er:YAG resurfacing laser (2.94-microm wavelength, 350-microsec pulse, 2 J, 3-5-mm
      spot). Twenty-five patients were treated with two passes to the full face and 3
      to 5 passes to the most affected aesthetic unit. At each follow-up visit, percent
      epithelialization, erythema, and swelling were graded, and the presence or
      absence of complications was noted. Clinical improvement was evaluated at 6
      months by optical profilometry on a subset of patients. Er:YAG resurfacing
      produced a transient whitening of dermis followed by a resumption of pink
      appearance. The surgical end point was judged by elimination of visible rhytids
      or presence of punctate bleeding. Bleeding from the dermal surface was
      encountered less than customarily in dermabrasion, but more than seen with carbon
      dioxide laser resurfacing. A moderate amount of tissue shrinkage was observable
      during the treatment. Mean period to full epithelialization was 6.9+/-0.97 days
      (range, 5-9 days). The mean duration of erythema (4.24+/-1.5 weeks) was
      relatively short compared with carbon dioxide resurfacing. Clinical improvement
      was 44+/-30% in the lateral canthal area and 55+/-22% in the upper lip area.
      There were no infections or hypertrophic scars. Hyperpigmentation and
      hypopigmentation was seen in 24% and 12% of patients respectively. Er:YAG
      resurfacing is a reliable means of obtaining rhytid improvement with less
      recovery time and duration of erythema compared with carbon dioxide resurfacing.
      The technique is significantly different from carbon dioxide resurfacing in
      selection of end point, number of passes, and energy settings.

PMID- 9555985
TI  - A balloon-assisted facialplasty technique.
AB  - An ongoing goal of aesthetic surgery is a reduction in complications and an
      improvement in reproducibility and speed. Balloon dissector devices have been
      used in other areas of surgery to achieve these goals. This report presents early
      clinical experience using a balloon dissector to elevate the skin flap in
      facialplasty. The first step in the technique is the creation of a tunnel from a
      small preauricular incision toward the oral commissure using scissors dissection.
      The balloon device is inserted into this tunnel and inflated. Unrolling the
      device elevates the skin flap in the cheek and neck area. Retroauricular
      dissection and final adjustment of flap size and shape is completed sharply.
      Subsequent superficial musculoaponeurotic system flap development, skin
      redraping, and closure is performed in a conventional fashion after customary
      facialplasty incisions are made. Comparison of complications, postoperative
      drainage, and time required for dissection and for hemostasis was made between a
      balloon-dissected side and a conventionally dissected side in 10 patients
      undergoing facialplasty. Ten additional patients were treated with balloon
      dissection bilaterally. Patients ranged in age from 45 to 73 years. Mean balloon
      dissection time was 1.4 minutes (range, 0.75-4 minutes). This produced an even
      flap thickness in the correct plane with few if any bleeding points. Mean total
      dissection time on the balloon side was significantly shorter-13.6 minutes
      compared with 27.8 minutes (p < 0.003) on the conventional side. Mean difference
      in time to hemostasis between conventional and balloon sides was 3.8 minutes (p <
      0.001). Mean total postoperative drainage (all drains removed at 24 hours) was
      13.8 cc on the balloon side and 18.8 cc on the conventional side (not
      significant, p=0.08). Less ecchymosis and swelling was observed on the balloon
      side compared with the scissors-dissected side. There were no skin losses,
      hematomas, infections, or nerve injuries on either side. Appearance of skin
      redraping was comparable on each side in all patients. Balloon dissection
      represents a promising alternative means of creating rapid, reproducible skin
      flap elevation in facialplasty, and is associated with a minimum of bleeding,
      ecchymosis, and swelling.

PMID- 9555986
TI  - Secondary use of the rectus muscle pedicle for TRAM flap volume deficiencies.
AB  - The residual subxiphoid rectus muscle pedicle was rotated secondarily to a
      position underneath the breast mound in 13 patients who had previously undergone
      transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction.
      The indications for this maneuver were the presence of a subxiphoid muscle bulge
      and a deficiency of volume or projection of the TRAM flap breast mound. This
      revisional surgery was performed at least 8 weeks after the TRAM flap, typically
      at the time of nipple-areolar reconstruction. Minor to moderate volume
      deficiencies were corrected and aesthetic improvement was substantial. There were
      no major complications. The danger of vascular compromise to the breast mound
      itself or to the remobilized muscle appears to be minimal, although the need for
      caution in the previously irradiated chest wall should be emphasized.

PMID- 9555987
TI  - Preferential use of the ipsilateral pedicle in TRAM flap breast reconstruction.
AB  - Breast reconstruction utilizing the ipsilateral transverse rectus abdominis
      musculocutaneous (TRAM) flap provides superior results when compared with
      contralaterally based reconstructions by preserving the medial inframammary fold
      and eliminating the perixiphoid bulge. Additionally, a longer pedicle can be
      obtained using the ipsilateral TRAM, thereby allowing greater mobility and
      flexibility during flap transposition. These findings are based on a
      retrospective review of 50 consecutive ipsilateral TRAM flap reconstructions in
      38 patients. The mean patient age was 45.4 years and mean follow-up was 8.6
      months. Thirty-two flaps were performed as immediate reconstructions and 18 flaps
      were delayed. No patient suffered total flap loss, whereas partial flap loss was
      observed in three flaps. One patient required suture removal to alleviate venous
      congestion of the flap. No patient developed a postoperative hernia, but 1
      patient required removal of a polytetrafluoroethylene onlay patch following graft
      exposure. This technique achieves aesthetically pleasing results with acceptable
      morbidity, allows greater flap mobility without disruption of the medial
      inframammary fold or creation of a perixiphoid bulge, and is our method of choice
      for TRAM flap breast reconstruction.

PMID- 9555988
TI  - Modifications of the Lejour vertical mammaplasty: analysis of results in 100
      consecutive patients.
AB  - The technique of vertical mammaplasty described by Madeline LeJour nearly ten
      years ago has been slow to gain wide acceptance in the United States. This is
      perhaps due to the misconception by many that this technique is more technically
      demanding or harder to reproduce and teach on a consistent basis. This paper
      describes several modifications to Madam LeJour's procedure, including the use of
      a template, a controlled excision, and a tension free nipple areola complex
      closure. When applied routinely, these modifications to the LeJour mammaplasty
      have produced predictable, reliable and extremely satisfying results.

PMID- 9555989
TI  - Breast reconstruction in previously irradiated patients using tissue expanders
      and implants: a potentially unfavorable result.
AB  - There exists a paucity of definitive information on the suitability of implant
      reconstructions in previously irradiated breast cancer patients. This
      controversial topic prompted a review of our prosthetic reconstructions in this
      select group of patients. A retrospective study of patients treated between 1976
      and 1993 with lumpectomy and radiation therapy for early breast cancer revealed
      67 patients with local recurrences. Nine of these patients (10 breasts) underwent
      a two-stage prosthetic reconstruction following a salvage mastectomy. The average
      age was 47.9 years. The mean dose of irradiation was 6,070 cGy. The average
      interval from radiation therapy to placement of a tissue expander was 4.6 years.
      In one patient (10%) the tissue expander extruded. The average follow-up for 8
      patients (9 breasts) who underwent exchange to a permanent prosthesis was 5.1
      years. In four reconstructions (40%) there was an uneventful postoperative
      course. Two cases (20%) were difficult to expand and the final result lacked
      projection. One patient (10%) developed an infection requiring removal of the
      permanent prosthesis. Two patients (20%) developed Baker class III or IV capsular
      contractures. Overall, in our group of 10 implant reconstructions, 60% of the
      patients resulted in either a complication or an unfavorable result.

PMID- 9555990
TI  - Split-twist FCR reconstruction for basal joint arthritis.

PMID- 9555991
TI  - Venous gangrene of the upper extremity.
AB  - Venous gangrene of the upper extremity is a rare entity and is the result of
      massive occlusion of all venous outflow of the extremity. The syndrome is
      strongly associated with hypercoagulable states including malignancy, low cardiac
      output states, and hereditary or acquired hematological abnormalities. Diagnosis
      can be straightforward but must be made early in the course of the process for
      treatment to be effective. Treatment has historically produced only modest
      results, and patients continue to suffer a high morbidity and mortality. We
      present a series of 6 patients with venous gangrene or impending venous gangrene
      of the upper extremities--a relatively large series. Two patients suffered from
      malignancy, 3 patients suffered from low-flow cardiac states, and 1 patient
      suffered from an overdose of calcium channel blockers. Hematological
      abnormalities included heparin-induced thrombocytopenia and thrombosis in 3
      patients, activated protein C resistance in 1 patient, and lupus anticoagulant in
      1 patient. Three patients experienced other major venous thrombotic
      complications, two of whom died (renal and cerebral venous infarction). Venous
      gangrene of the upper extremity remains a rare occurrence but one in which early
      identification and intervention may lead to improved outcomes.

PMID- 9555992
TI  - Use of a multiplanar distracter for the correction of a proximal interphalangeal
      joint contracture.
AB  - Proximal interphalangeal (PIP) joint contractures are common complications in
      hand injuries and conditions such as Dupuytren's contracture. Conventional
      treatment such as splinting and serial casting may result in inadequate
      improvement. Operative release of the contracture may be complicated by
      neurovascular overstretch with injury to the digital nerves or vascular
      compromise. Gradual distraction of the contracted joint may prevent this
      neurovascular injury. The multiplanar distracter was designed for three
      dimensional distraction of the mandible. Distraction may be obtained in the X, Y,
      or Z planes. With this device, the angular relationship between two planes may be
      altered. A 22-year-old male with a PIP joint contraction following replantation
      failed conventional treatment for release. With the use of a multiplanar
      distracter, the flexion contraction was reduced from 95 degrees to a more
      functional 30 degrees using gradual angular distraction. The angle between the
      proximal and middle phalanges were gradually changed using the ability of the
      distracter to change the angular relationship in the X-Y plane. At 3 and 6 months
      postdistraction, the patient has maintained his 30-degree flexion angle. The
      multiplanar distracter is a simple technique that may be useful for the treatment
      of PIP joint contractures that fail conventional therapy.

PMID- 9555994
TI  - The total volar forearm musculocutaneous free flap for reconstruction of extended
      forequarter amputations.
AB  - Forequarter amputation is performed for resection of large, invasive tumors of
      the shoulder girdle region. A substantial defect can usually be closed with local
      or regional flaps; however, a subset of the forequarter amputation group has
      emerged at this institution with more complex issues. These patients have
      extensively more invasive posterior tumors, some with chest wall/rib invasion.
      Local/regional flaps in these situations are inadequate, and free tissue transfer
      is the only viable option. The forequarter specimen can sometimes be used as a
      donor site, thereby eliminating the usual donor site morbidity. Variations of the
      total forearm free flap have been sparsely described in the literature--the
      majority being case reports of either pure fasciocutaneous or "filet of forearm"
      flaps. We report a series of 4 patients treated over a 5 year period at this
      institution using the previously undescribed total volar forearm musculocutaneous
      free flap based on the brachial artery and its venae comitantes. This flap
      includes the entire musculature of the volar forearm with fasciocutaneous
      extensions on either side of the musculocutaneous unit. All potentially ischemic
      dorsal musculature is discarded, leaving a flap that has central bulk and a
      relatively large dimension. The entire flap remains extremely well vascularized,
      and a substantial surface area of as much as 45 x 25 cm can be attained. A
      pedicle as long as 20 cm can be dissected as far proximally in the arm as is
      oncologically safe. A single artery and vein are anastomosed to either the
      intrathoracic or neck vessels. All four flaps survived completely with
      uncomplicated wound healing. The total volar forearm musculocutaneous flap is
      extremely well vascularized and highly reliable. The flap as described provides
      the ideal combination of large surface area, muscle bulk, and long vascular
      pedicle. It can be dissected rapidly to minimize ischemic time and could
      therefore be applicable to traumatic forequarter amputations. It has become the
      flap of choice for reconstruction of extended oncological forequarter amputation
      defects.

PMID- 9555993
TI  - Soft-tissue complications of intra-arterial chemotherapy for extremity sarcomas.
AB  - High-grade sarcomas have a high rate of local recurrence as well as distant
      metastases. This has led to the development of intra-arterial chemotherapy (IAC)
      as part of a multimodal approach to control local disease and/or reduce the
      extent of surgical resection. Intra-arterial catheters are positioned by an
      interventional radiologist into the feeding vessels of the tumor. Adriamycin and
      5-fluorodeoxyuridine are infused intra-arterially. Cisplatinum, with or without
      granulocyte colony stimulating factor, is given systemically. Patients usually
      experience acute self-limited soft-tissue inflammation in the treated area. In
      our experience of 118 patients, 3 patients experienced soft-tissue necrosis that
      required excision and reconstruction. The first was treated for synovial sarcoma
      of a metatarsal. After IAC with Adriamycin, she sloughed the skin, subcutaneous
      tissue, and some of the posterior compartment musculature of her calf. This
      tissue was debrided. A gastrocnemius flap and skin graft were used for coverage.
      She is free of disease and ambulatory. The second patient was treated with IAC
      Adriamycin for a radial head chondrosarcoma. She developed soft-tissue slough,
      which became infected with Pseudomonas. She required extensive debridement of the
      skin, subcutaneous tissue, and muscle, and was subsequently reconstructed with a
      latissimus flap and a split-thickness skin graft (STSG). She later developed a
      local recurrence requiring amputation. The latissimus was elevated and used to
      cover the distal stump. She also is free of disease. The third patient was
      treated with IAC Adriamycin for Ewing's sarcoma of the right femur. This was
      complicated by fat necrosis and persistent pain. Subsequent radiotherapy only
      worsened her symptoms. She underwent wide excision and muscle flap/STSG repair,
      which relieved her pain. She is currently ambulatory and free of disease. In
      conclusion, as the use of IAC continues, its complications may become more
      common. Our experience with this previously unknown entity is illustrated and
      therapeutic options are discussed.

PMID- 9555995
TI  - The radial forearm osteocutaneous "sandwich" free flap for reconstruction of the
      bilateral subtotal maxillectomy defect.
AB  - Complex resections of the maxilla produce a three-dimensional defect that can be
      difficult to reconstruct using autogenous tissue without utilizing a free tissue
      transfer. The osteocutaneous flaps that have been described for reconstruction of
      this area have been the scapula, iliac crest, and fibula, which are often
      hampered by their bulkiness and less than ideal intraoral lining. The bilateral
      subtotal maxillectomy defect is particularly difficult to reconstruct because it
      requires restoration of the bony framework of the midface as well as the
      restoration of the palatal and nasal lining. We present a new technique for
      reconstruction of this type of defect using the osteocutaneous radial forearm
      free flap. Two patients with bilateral subtotal maxillectomy defects, in whom the
      entire hard palate and maxillary arch were resected, underwent primary
      reconstruction. The bone from the osteocutaneous flap was osteotomized and
      contoured to recreate the maxillary arch. The large skin island was folded around
      the bone, as in a sandwich, and used to replace the palatal and nasal lining.
      This sandwiched osteocutaneous flap allowed for secure fitting of a dental
      prosthesis and the future possibility of osteointegrated implants. Long-term
      stability of the bone without retrusion was achieved with an excellent functional
      and aesthetic outcome. The radial forearm osteocutaneous free flap is ideal for
      the reconstruction of the maxillary infrastructure in that (1) it provides bone
      and thin, pliable skin in the correct proportions; (2) the described "sandwich"
      technique restores an excellent functional and aesthetic state; and (3) dental
      rehabilitation can be further improved by using either a prosthesis or
      osteointegrated implants.

PMID- 9555996
TI  - Body image concerns of reconstructive surgery patients: an underrecognized
      problem.
AB  - This study assessed the body image concerns of reconstructive plastic surgery
      patients. Forty-three reconstructive surgery patients completed two measures of
      body image. Responses were compared with a group of patients seeking cosmetic
      procedures. The two groups did not differ in the degree of dissatisfaction with
      their overall appearance or dissatisfaction with the specific feature for which
      they were seeking surgery. Reconstructive patients did consider themselves less
      healthy and less invested in their appearance than did cosmetic patients. Seven
      of the reconstructive surgery patients (all scar revision patients) reported a
      level of dissatisfaction and preoccupation consistent with the psychiatric
      diagnostic of body dysmorphic disorder. These results underscore the importance
      of screening for body image dissatisfaction in persons with an objective
      deformity. Plastic surgeons are in an optimal position to identify body image
      concerns in these patients and provide appropriate referrals for psychotherapy.

PMID- 9555997
TI  - Free radial artery grafts: surgical technique and results.
AB  - In the search for alternative conduits, the use of radial artery (RA) grafts has
      found renewed interest. This study sought to evaluate prospectively the
      perioperative morbidity, including the postoperative complications in the donor
      forearm, and mortality in the routine use of RA grafts in coronary artery bypass
      surgery. Data were obtained prospectively on 200 consecutive patients who
      underwent coronary revascularization using at least one RA graft from January
      1995 to April 1997. The mean age of the patents was 61.9+/-10.5 years (mean+/
      standard deviation [SD]). The RA was obtained from one forearm in 197 patients
      and both forearms in 3 patients. Two patients (1%) required exploration for donor
      site hematomas, 4 patients (2%) had temporary perioperative dysesthesias in the
      region of the lateral cutaneous nerve of the forearm, and none had donor site
      wound infection. Two patients (1%) had a myocardial infarction with
      electrocardiographic changes in the areas grafted by the RA in the immediate
      postoperative period, indicating graft failure. The two deaths in the series were
      due to comorbid factors. Our data suggest that the RA is a safe and suitable
      conduit for coronary revascularization, and it provides good clinical results.
      Long-term follow-up of these patients is necessary to confirm the patency of RA
      conduits. Free RA grafts have the potential for use in other areas of surgery
      where a conduit is necessary for revascularization procedures.

PMID- 9555998
TI  - In vitro prefabrication of human cartilage shapes using fibrin glue and human
      chondrocytes.
AB  - We report the first generation of human cartilage from fibrin glue using a
      technique of molding chondrocytes in fibrin glue developed in our laboratory.
      Human costal chondrocytes were suspended in cryoprecipitate and polymerized into
      a human nasal shape with bovine thrombin. After culture in vitro for 4 weeks,
      this construct was implanted subcutaneously into a nude mouse. The final
      construct harvested after 4 weeks in vivo demonstrated some preservation of its
      original features. Histological analysis showed features of native cartilage,
      including matrix synthesis and viable chondrocytes by nuclear staining.
      Biochemical analysis demonstrated active matrix production. Biomechanical testing
      was performed. To our knowledge this is the first reported creation of human
      cartilage from fibrin glue, and the first creation of human cartilage in vitro.
      This technique may become a promising means of engineering precisely designed
      autogenous cartilage for human reconstruction.

PMID- 9555999
TI  - Comparison of the effects of ischemic preconditioning and surgical delay on
      pedicled musculocutaneous flap survival in a rat model.
AB  - Both surgical delay (SD) and ischemic preconditioning (IP) have been shown to be
      effective in improving the survival of pedicled musculocutaneous flaps. The goal
      of our study was to determine the effects of IP and SD, separately and together,
      on the survival of pedicled transverse rectus abdominis musculocutaneous (TRAM)
      flaps in a rat model. Thirty-two male Sprague-Dawley rats were divided into four
      groups of 8 rats each: (1) control, (2) 2-week SD, (3) IP, and (4) SD plus IP. A
      TRAM flap was elevated in each rat. Flap viability was assessed on the fifth
      postoperative day by computerized video planimetry. Mean area of flap survival
      was compared between the control, IP, SD, and SD plus IP groups using analysis of
      variance and Student's t-test. Improvement in surface area survival was seen in
      musculocutaneous flaps subjected to IP, SD, and SD plus IP compared with the
      control. IP and SD improved survival 1.3 and 1.4 times the control area
      respectively. Differences between treatment and control flaps were statistically
      significant (p < 0.04). In addition, the combination of SD plus IP improved
      survival by 1.8 times, which is statistically different from controls and from
      either technique individually (p < 0.002). IP and SD have similar efficacy in
      improving survival in this musculocutaneous flap model. The effects of IP and SD
      appear to be additive. The advantage of IP over SD is that IP can be performed
      during the same operative session as the flap elevation and only adds 1 hour to
      the surgical procedure.

PMID- 9556000
TI  - Ischemic preconditioning of musculocutaneous flaps: effects of ischemia cycle
      length and number of cycles.
AB  - Previous work in our laboratory has indicated that ischemic preconditioning
      improves musculocutaneous flap survival 2.5 times that of the control flap area
      when the flaps are subsequently subjected to 4 hours of global ischemia. The
      preconditioning protocol used in this study was arbitrarily designed to be 10
      minutes of pedicle clamping followed by 10 minutes of reperfusion. This sequence
      was repeated for three cycles with a total preconditioning time of 1 hour. There
      are no published works comparing different preconditioning protocols in
      musculocutaneous flaps. The goal of this study was to determine if the ischemic
      cycle time and the number of cycles influenced the effectiveness of ischemic
      preconditioning. Fifty-one male Sprague-Dawley rats were divided into one control
      and six treatment groups of 6 to 10 animals in each group. A transverse rectus
      abdominis musculocutaneous flap based on the inferior epigastric vessels was
      elevated in each animal. Flaps were preconditioned by pedicle clamping and
      reperfusion for either 5 or 10 minutes per cycle. This was repeated for one, two,
      or three cycles. Controls were simply perfused for 30 minutes. Each flap was then
      subjected to 4 hours of global ischemia. Flap surface survival area was
      calculated on the fifth postoperative day by computerized video planimetry.
      Differences in survival areas between control and preconditioned flaps were
      compared using analysis of variance and t-tests. There was an overall statistical
      significance in the comparison of flap survival of preconditioned flaps with that
      of controls. A single 5-minute cycle improved flap survival 2.5 times the mean
      control area. Two and three 5-minute cycles resulted in a reduction of the
      preconditioning effect, with flap survival no different than controls. Ten-minute
      preconditioning cycles increased flap survival 1.5 to 3 times the mean control
      area. Flap survival was improved by increasing the number of 10-minute cycles.
      Cycle time and number of cycles have definite effects on the survival areas of
      preconditioned musculocutaneous flaps. Ischemic preconditioning with 10-minute
      cycles is superior to 5-minute cycles. Three cycles of 10-minute preconditioning
      is statistically superior to one or two cycles. Future studies are planned to
      study four or more cycles and longer cycle times.

PMID- 9556001
TI  - The effect of prolonged clamping and vascular stasis on the patency of arterial
      and venous microanastomoses.
AB  - During free tissue transfer, an artery and one or two veins must be sutured.
      Either the artery or the vein can be repaired first, but the optimal order of
      vascular repair has not been established. Maintaining a clamp on a vessel is
      associated with vessel injury, and releasing the clamp may cause bleeding and
      vascular stasis. The purpose of this study was to determine if the order of
      vessel repair and the length of vascular clamping affects surgical outcome. Free
      flaps were created on Sprague-Dawley rats (400-450 g) as follows: Bilateral
      abdominal skin flaps (3 x 3 cm) based on the superficial inferior epigastric
      vessels were elevated. The femoral artery and vein were tied and divided distal
      to the branching of the inferior epigastric vessels. Proximal to the branching,
      the artery and vein were divided. The animals were then randomized into four
      groups as follows: In group I (N=16), the artery was repaired and then the clamps
      were released to revascularize the flap. Venous stasis occurred as the vein was
      being repaired because of the venous clamp. In group II (N=15), the artery was
      repaired, but the clamp was maintained to prevent blood from coming in contact
      with the fresh arterial anastomosis and to prevent venous stasis. The vein was
      then repaired. In group III (N=15), the vein was repaired first but the venous
      clamp was not released until the artery was repaired. In group IV (N=15), the
      vein was repaired first and the clamps were released, allowing venous blood to
      contact the fresh anastomosis while the artery was being repaired. After final
      clamp removal, all anastomoses were assessed immediately for evidence of
      thrombosis. Five days postoperatively the skin flap was evaluated for evidence of
      necrosis and the anastomosis was inspected for evidence of late thrombosis. The
      anastomoses were resected for histopathological evaluation. Flap success was
      compared between groups using chi-squared analysis. Eleven of 16 flaps failed
      (69%) in group I, and 3 of 15 flaps failed (20%) in each of groups II, III, and
      IV. Statistical significance was reached in comparing group I with the other
      three groups (p < 0.01). All failures in group I were caused by immediate venous
      thrombosis. The other failures were secondary to arterial thrombosis.
      Histopathological analysis failed to demonstrate any differences between the
      groups. According to these results, arterial repair followed by clamp release
      prior to the completion of the venous repair results in a low success rate,
      probably secondary to venous stasis within the draining vein while the venous
      anastomosis is being completed. If the arterial repair is performed first, then
      it is recommended that the arterial clamp be maintained until the venous repair
      is completed. If the vein is repaired first, then it can be clamped or unclamped
      with similar results.

PMID- 9556002
TI  - Reflections of a career in progress.

PMID- 9556003
TI  - Exercise and cystic fibrosis: the search for a therapeutic optimum.

PMID- 9556004
TI  - RSV, recurrent wheezing, and ribavirin.

PMID- 9556005
TI  - The anaerobic threshold in cystic fibrosis: comparison of V-slope method, lactate
      turn points, and Conconi test.
AB  - Physical exercise can improve sputum clearance in patients with cystic fibrosis
      (CF). To set up individual training protocols it is desirable to know the
      anaerobic threshold (AT). Established methods such as blood lactate measurements
      and ergometry can only be performed in specialized centers. Conconi showed that
      the heart rate threshold (HRT), i.e., the deflection point from the linear
      relationship between work load and heart rate, correlated significantly with the
      AT in healthy adults. To assess the reliability of the HRT in CF, we performed
      ergometry in 32 CF patients (mean age, 21.0 +/- 5.5 years; mean Shwachman score,
      77.8 +/- 12.0) according to the Conconi protocol. The HRT was compared with the
      aerobic threshold (AeT) as determined by the V-slope method and with two turn
      points in the lactate performance curve (LTP1, LTP2). An HRT could be obtained in
      only 17 of the 32 patients (53%). In these 17 patients there was a significant
      correlation between HRT and the other thresholds, but the absolute values for the
      AT differed considerably: The mean HRT was 132% higher than the AeT according to
      Beaver, 107% higher than LTP1, and 19% higher than LTP2. Exercise protocols that
      rely solely on the HRT in CF will lead to excessive exertion during exercise
      training programs in these patients. According to these results the HRT of
      Conconi is not a suitable method to determine appropriate exercise levels in CF
      training programs and might even be harmful in CF patients. These results also
      indicate the need to test the reliability of a diagnostic procedure that has been
      developed only for healthy people.

PMID- 9556006
TI  - Reduced long-term respiratory morbidity after treatment of respiratory syncytial
      virus bronchiolitis with ribavirin in previously healthy infants: a preliminary
      report.
AB  - Previously healthy infants less than 6 months of age with severe respiratory
      syncytial virus bronchiolitis who required hospitalization were identified from
      hospital records. Infants had been treated either conservatively (control group,
      n = 19) or with ribavirin added to conservative management (study group, n = 22).
      All infants underwent a 1-year follow-up after the initial illness. There was a
      significant reduction in the prevalence of reactive airway disease in the group
      treated with ribavirin (P < 0.05) compared with the control group, both in terms
      of the proportion of patients developing airway reactivity (59% vs. 89%) and the
      number of episodes of reactive airway disease (31 vs. 70). Our data suggest that
      ribavirin reduces the prevalence of airway reactivity.

PMID- 9556007
TI  - Comparison of responses to an asthma symptom questionnaire (ISAAC core questions)
      completed by adolescents and their parents. SCARPOL-Team. Swiss Study on
      Childhood Allergy and Respiratory Symptoms with respect to Air Pollution.
AB  - The primary objective of the study was to determine the impact of the identity of
      the respondent (parents versus adolescents) on prevalence estimates of asthma
      symptoms in Swiss adolescents. In addition, factors influencing agreement between
      parents' and adolescents' responses to the same questions were analysed. One
      thousand three hundred and seventy-four (78.4%) adolescents, aged 14 years, self
      completed a questionnaire at school based on the International Study of Asthma
      and Allergy in Childhood (ISAAC) core questions on wheezing and asthma. The same
      questions were incorporated into a questionnaire to be completed by the parents
      at home. The adolescents' self-reported prevalence rates of current asthma
      symptoms and "asthma ever" were significantly higher than those obtained from the
      parental questionnaires. 856 (62.6%) parental questionnaires were filled in by
      parents without the help of the adolescents, 460 (37.4%) were completed by
      parents and adolescents and 51 (3.7%) were completed by the adolescents without
      the parents. Prevalence rates were higher when parents and adolescents completed
      the questionnaire jointly than when questionnaires were completed by parents
      alone. The level of agreement between parental and self-completed questionnaires
      was moderate to low (kappa coefficients 0.22-0.68). Agreement between parental
      and adolescents reports of asthma symptoms was best when questionnaires were
      completed jointly by parents and adolescents, when the adolescent was a girl,
      when a family history of asthma was recorded, when the adolescent was a non
      smoker, and when the parental education was high. We conclude that the higher
      reporting of prevalence rates of current asthma symptoms by adolescents compared
      to reporting by their parents demonstrates the need to take the respondent to a
      questionnaire into account when comparisons are made between prevalence studies.
      The results also suggest that factors related to the family milieu influence
      symptom reporting.

PMID- 9556008
TI  - Serum eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in
      childhood asthma: the influence of atopy.
AB  - The purpose of this study was to determine the value of serum measurements of
      eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in diagnosing
      asthma in children, and to investigate the influence of concomitant allergic
      diseases and atopic sensitization, assessed by skin prick tests (SPT), on these
      markers. ECP and EPX were determined in 36 children with asthma, in 33 children
      with other symptoms from lower airways disease (OSLA), and in 166 control
      children. Sixteen children with asthma but no anti-inflammatory therapy had
      significantly higher concentrations of ECP and EPX (ECP: 27.5 microg/L, P <
      0.001; EPX: 59.9 microg/L, P < 0.001) than the control children (ECP: 11.2
      microg/L; EPX: 26.2 microg/L). In the 20 children on anti-inflammatory therapy,
      ECP values were similar to those of controls. The children with OSLA (ECP: 13.6
      microg/L, P < 0.01; EPX: 47.2 microg/L, P < 0.001) differed significantly from
      controls. When using the value of 24.7 microg/L (97.5 percentile in the 68 non
      atopic controls) as a pathologic upper limit for ECP, 10 (63%) of the 16
      asthmatic children on no maintenance medication, two (10%) of the 20 asthmatics
      on maintenance therapy, and 11 (33%) of the 33 children with OSLA had high ECP;
      the same figure was only 18 (11%) in the 166 control children. Both ECP and EPX
      had a significant association with allergic disorders and with SPT reactivity. In
      multivariate logistic regression analysis, an elevated ECP was significantly
      associated with asthma (OR 2.3, 95%CI 1.1-4.9) and atopic dermatitis (2.9, 1.2
      6.9), and an elevated EPX was significantly associated with asthma (2.61, 1.19
      5.74) and allergic rhinoconjunctivitis (5.23, 1.46-18.73). We conclude that serum
      concentrations of both ECP and EPX are higher in asthmatic than in healthy
      children. However, other allergic diseases, such as allergic rhinoconjunctivitis,
      atopic dermatitis, and allergic skin sensitization also raise the concentrations
      of these markers. This limits their usefulness in the diagnosis of childhood
      asthma.

PMID- 9556009
TI  - Thoracoabdominal motion in newborns during ventilation delivered by endotracheal
      tube or nasal prongs.
AB  - Preterm infants have asynchronous thoracoabdominal motion (TAM) secondary to a
      highly compliant chest wall and different lung mechanics compared to term
      infants. We compared TAM during continuous positive airway pressure (CPAP)
      administered through an endotracheal tube (ETT-CPAP) or nasal prongs (nasal
      CPAP), and during synchronized intermittent mandatory ventilation administered by
      nasal prongs (nasal-SIMV) in 14 preterm newborn infants. Asynchrony of TAM was
      quantified by measuring relative motion of chest wall and abdomen with strain
      gauges and calculating phase angles (theta). Phase angles were lower during nasal
      SIMV compared to nasal-CPAP or ETT-CPAP (P < 0.05), and lower during nasal-CPAP
      compared to ETT-CPAP (P < 0.05). The reduced TAM asynchrony during nasal-SIMV and
      nasal-CPAP may be due to elimination of resistance of the ETT and/or effective
      stabilization of the chest wall. These data suggest that nasal-SIMV may be an
      effective mode of respiratory support for preterm infants requiring minimal
      ventilatory support.

PMID- 9556010
TI  - Effect of neonatal surfactant therapy on lung function at school age in children
      born very preterm.
AB  - Our aim was to evaluate long-term effects of exogenous surfactant therapy on
      pulmonary functional outcome in children born very preterm. We examined 40
      children aged 7-12 years who were born before 30 weeks of gestation with an
      immature surfactant system, and were randomized to one of three treatment groups:
      human surfactant given at birth (prophylactic), human surfactant given after
      development of neonatal respiratory distress syndrome (rescue), and placebo (air)
      treatment. Spirometric parameters of preterm born children were compared with
      those of 20 children born at term. In addition, spirometric parameters were
      monitored twice daily for 4 weeks using a home spirometer. All spirometric
      parameters were significantly lower in the preterm groups than in the controls,
      except for the forced vital capacity (FVC) in the prophylactically treated group.
      Bronchial obstruction was found in 53% of the prophylactically treated group, in
      36% of the rescue group, in 67% of the placebo group, and in 0% of the control
      group. Peak expiratory flow (PEF) and FVC values were higher in those children
      who received surfactant compared with the placebo group (P < 0.05). In 16
      children (40%) born preterm, a beta2-agonist induced an increase in PEF > or =
      15% at least three times during 2 weeks of home monitoring; eight children (20%)
      had abnormal diurnal PEF variation. Multiple regression analysis indicated that
      the independent variables associated with favorable outcomes in spirometric
      parameters were surfactant therapy (P = 0.012-0.045) and short intubation time
      after birth (P = 0.0009-0.0044). Bronchial obstruction, responsiveness to a beta2
      agonist, and high diurnal PEF variation are common in children born before 30
      gestational weeks. Surfactant supplementation reducing the need for mechanical
      ventilation or supplementary oxygen after birth may decrease the severity of
      immaturity related bronchial obstruction in childhood.

PMID- 9556011
TI  - Changes in pulmonary artery pressure during the acute phase of respiratory
      distress syndrome treated with three different types of surfactant.
AB  - We studied the changes in acceleration time/right ventricular ejection time ratio
      (AT/RVET; indicative of changes in pulmonary artery pressure) calculated from
      Doppler ultrasound examinations performed before and 1, 6, and 12 h after the
      first and second doses of surfactant following the administration of each of
      three different surfactants during the acute phase of the respiratory distress
      syndrome. Maximum fractional inspired oxygen concentration (F(I,O2)) and peak
      inspiratory pressure (PIP) were recorded during each 4 h period from birth for
      the first 24 h and subsequently every 24 h until 72 h. Eighty-three infants were
      studied. Fifty patients weighing > 1 kg received Exosurf (n = 29) or ALEC (n =
      21) and 33 weighing < or = 1 kg received Exosurf (n = 22) or Survanta (n = 11).
      The AT/RVET rose rapidly after administration of all three surfactants. There was
      no significant difference in the change in AT/RVET between those > 1 kg who
      received Exosurf and those who received ALEC (a synthetic surfactant). Similarly,
      there was no difference between those infants < or = 1 kg who received Exosurf
      and those who received Survanta. The F(I,O2) requirements, but not PIP, were
      lower in those infants who received Survanta at 12 and 20 h compared with those
      who received Exosurf. There was no significant difference in the F(I,O2) or PIP
      requirements between infants > 1 kg who received Exosurf compared with those who
      received ALEC. The rise in AT/RVET found in this study after administration of
      ALEC, Exosurf, or Survanta suggests that similar and rapid falls in pulmonary
      artery pressure occur after all three surfactant administrations, despite the
      difference in clinical response demonstrated between Exosurf and Survanta.

PMID- 9556012
TI  - Rate of surfactant administration influences lung function and gas exchange in a
      surfactant-deficient rabbit model.
AB  - The aim of this study was to test whether the effect of surfactant treatment on
      lung function in a surfactant-deficient animal model can be influenced by the
      rate at which surfactant is administered. Surfactant deficiency was induced in 18
      New Zealand white rabbits (weighing approx. 1 kg each) by lung lavage with normal
      saline. The arterial/alveolar oxygen ratio (a/A ratio), functional residual
      capacity (FRC), dynamic compliance of the respiratory system (Crs), tidal volume
      (V(T)), alveolar portion of the tidal volume (V(A)) and arterial P(CO2)
      (P(a,CO2)) were measured before and after lavage and 15, 30, 60, 90, and 120 min
      after administration of a single dose of surfactant (Survanta, 100 mg/kg). Two
      surfactant administration protocols were compared over a 2-h interval: an
      infusion lasting 4 min and an infusion over 2 min. Both administrations were
      given during continuous mechanical ventilation. The six lung function and gas
      exchange parameters improved significantly following surfactant administration
      over 2 min compared with a control group. However, only the a/A ratio and V(A)
      improved following the 4-min protocol. Comparison of the two intervention
      protocols yielded significantly differences in V(A) and P(a,CO2), favoring the
      shorter administration. These results support the hypothesis that fast (2 min)
      administration of surfactant will improve its distribution to formerly collapsed
      alveoli and results in better lung function, improved ventilation, and (to a
      lesser extent) better oxygenation than prolonged infusions (4 min).

PMID- 9556013
TI  - A rebreathing method to determine carbon monoxide diffusing capacity in children:
      reference values for 6- to 18-year-olds [corrected] and validation in adult
      volunteers.
AB  - The diffusing capacity of carbon monoxide (D(L,CO)) and its value normalized to
      alveolar volume (D(L,CO)/V(A)) are usually estimated with the single breath
      method at total lung capacity (TLC). Severely ill patients and small children are
      not able to deliver a satisfactory vital capacity (VC) or hold their breath for
      10 s at TLC. The aim of this study was to develop a rebreathing procedure in
      which diffusing capacity can be determined during spontaneous tidal breathing.
      The conventional rebreathing method during hyperventilation was modified so that
      rebreathing volume and gas concentrations were kept constant by CO2 absorption
      and O2 supplementation. In adult healthy volunteers and in patients who were able
      to perform both tests, the diffusion indices obtained with this rebreathing
      method during resting ventilation were compared with those obtained by the single
      breath method. Predicted (reference) values for rebreathing D(L,CO) and
      D(L,CO)/V(A) for children were determined. D(L,CO)/V(A) decreased with alveolar
      volume (V(A)) and increased with alveolar ventilation (V'(A)). In adults at V'(A)
      above 35 L x min(-1) rebreathing D(L,CO)/V(A) was similar to single breath
      D(L,CO)/V(A) at similar alveolar volumes. The D(L,CO)/V(A) relative to their
      corresponding reference values were the same for both methods in adult patients,
      irrespective of ventilation distribution disturbances. In children the newly
      described diffusing capacity obtained by the rebreathing method during resting
      ventilation can serve as a valuable index to assess and follow a diffusion
      disorder.

PMID- 9556014
TI  - Detection of tidal expiratory flow limitation in infants with cystic fibrosis: a
      pilot study.

PMID- 9556015
TI  - Capitol Hill update.

PMID- 9556016
TI  - R29 to RO1 transition at NIH.

PMID- 9556017
TI  - The Henry Gray Award.

PMID- 9556018
TI  - To dissect or not to dissect?

PMID- 9556019
TI  - Marcello Malpighi and the foundations of functional microanatomy.

PMID- 9556020
TI  - Anatomy of the shaken baby syndrome.
AB  - Shaken baby syndrome refers to the constellation of nonaccidental injuries
      occurring in infants and young children as a consequence of violent shaking. The
      typical victim of shaken baby syndrome is a male infant younger than six months
      of age who is alone with the perpetrator at the time of injury. Occurrence of the
      syndrome is unrelated to race, gender, socioeconomic status, or education. The
      characteristic injuries observed in shaken baby syndrome include subdural
      hemorrhages, retinal hemorrhages, and fractures of the ribs or long bones.
      Although each of these injuries may result from violent shaking of the victim,
      the most severe brain injuries result from the addition of a forceful impact of
      the infant's or child's head against a firm surface. The unique anatomic features
      of the infant's head and skeletal system, which account for the type and pattern
      of injuries observed in shaken baby syndrome, are emphasized in this article.

PMID- 9556021
TI  - Exploring development and disease through germ-line genetic engineering in the
      mouse.
AB  - New developments in mouse genetics have transformed the field of genetics from a
      reactive to a proactive science. Current technologies in transgenesis, chromosome
      engineering, and saturation mutagenesis are introduced. These approaches permit
      the creation of new mutations and consequent mutant phenotypes that facilitate
      both the understanding of functions of existing genes and the search for
      previously unidentified genes affecting important phenotypes in all mammals.

PMID- 9556022
TI  - The bearable lightness of being: bones, muscles, and spaceflight.
AB  - Bones and muscles support and move the body. Tendons link the two tissues and
      serve as a mechanism for transfer of forces from muscle to bone. These three
      tissues interact and respond to periods of activity or inactivity with
      appropriate alterations in structure and strength. There is substantial evidence
      that an environment devoid of mechanical stress on the skeleton (such as reduced
      gravitational forces during spaceflight, a "microgravity environment") produces
      direct effects on bone structure and function. There is little agreement
      concerning the biologic mechanisms for these atrophic changes. Changes in fluid
      balance and distribution coincident to spaceflight also affect muscles and bones
      by an unknown mechanism. Tendon-bone junctions are presumed to be spared from the
      effects of spaceflight. However, recent evidence from rodents suggests that
      spaceflight profoundly effects both the skeleton and the tendon-bone junctions.
      These effects include cortical bone resorption, which undermines the Sharpey's
      fibers that anchor the tendon to the bone matrix. The challenge to biomedical
      scientists is to devise methods for protecting spaceflight crews from these
      atrophic changes; such protection would allow for longer and more extensive
      spaceflights.

PMID- 9556023
TI  - Anatomy education in a changing medical curriculum.
AB  - How we educate students in the first two years of medical school is changing at
      many institutions. Effective medical education should be viewed as a continuum,
      integration of the basic sciences and clinical medicine should occur throughout
      the curriculum, and self-directed, life-long learning should be emphasized.
      Curricular revision may be appropriate if these fundamental concepts are absent.
      The principles of three curricular models are discussed: traditional, problem
      based, and systems-oriented. The ideal curriculum may draw from each of these: A
      truly integrated curriculum. However, the curricular model chosen must meet the
      needs of the institution and its students. As anatomists we should not shy away
      from this process of change. With progressive educational approaches, we can be
      leaders in this climate of curricular reform. Anatomy courses are laboratory
      based and the laboratory is an outstanding small group, faculty/student
      interactive opportunity. However, we must show flexibility and innovation in our
      educational approaches whatever the curricular design being proposed.

PMID- 9556024
TI  - Neurodegeneration and aging: role of the second genome.
AB  - The latest Health Report of the World Health Organization predicts a significant
      increase in the age of human populations over the next two decades. In the
      developed world, at least 20% of the population will be older than 65 years. This
      development together with the as yet unknown etiology of many neurodegenerative
      disorders has caused an increased interest in the biology and pathophysiology of
      mitochondria. Dysfunction of mitochondria has been linked to both normal aging
      and neurodegenerative disorders, with the latter occurring much more frequently
      at higher age. Specifically, genetic defects in mitochondria have been shown to
      accumulate during life, and certain mutations of mitochondrial genes have been
      implicated in the etiology of Parkinson's and Alzheimer's diseases. In addition,
      a large number of new mitochondrial diseases have been identified following the
      first description of mitochondrial mutations 10 years ago. While there can be
      little doubt that DNA defects of mitochondria play a role in aging, specific
      mutations of mitochondrial genes underlying Parkinson's or Alzheimer's diseases
      remain to be identified. There is evidence, however, that mutations of the
      mitochondrial genome may increase the susceptibility to neurodegeneration.

PMID- 9556025
TI  - Involvement of cytokines in normal CNS development and neurological diseases:
      recent progress and perspectives.
AB  - Cytokines have been recognized to play an important role both in normal
      development of the brain, when they act as neurotrophic factors, as well as
      following injury. While both the cytokines and their receptors are synthesized
      and expressed in the brain normally (albeit at low levels), it has become clear
      that elevated levels are associated with many neurological disorders. In this
      review, we have chosen to present the data for only a few of the cytokines,
      including interleukin-1beta, interleukin-3, interleukin-6, interferon-gamma,
      transforming growth factor-beta, and tumor necrosis factor-alpha. Data are
      presented that suggest roles they may play in human disorders, including stroke,
      multiple sclerosis, Alzheimer's disease, and several psychiatric disorders. The
      results in human disease are compared with results obtained in a variety of
      transgenic animal models. The mouse models have very different disorders
      depending on whether a cytokine is overexpressed either peripherally or in either
      astrocytes or neurons. The potential significance of this to the understanding of
      human disease is discussed.

PMID- 9556026
TI  - Differentiation of oligodendrocyte occurs in contact with astrocyte.
AB  - We have generated stage-specific oligodendrocytes, which are identified as
      immature oligodendrocytes by the expression of specific markers. These cells were
      generated by using 3 types of intrinsic and extrinsic factors for influencing the
      characteristics of oligodendrocyte-lineage cells. The factors included 10% serum
      in the medium to induce cell proliferation, bFGF in serum-free medium to increase
      survival and induce differentiation, and 0.25% trypsin to remove
      nonoligodendrocyte lineage cells. We have also demonstrated that it is possible
      to supply a huge amount of homogeneous populations of stage-specific immature
      oligodendrocytes after 35 days' culture. The maturation of these cells is
      controlled by interacting with astrocytes in vitro, resulting in the expression
      of MBP isoforms (14.0 and 18.5 kDa) that may participate in mature
      oligodendrocyte membrane compaction.

PMID- 9556027
TI  - Anatomical distribution of the chemorepellent semaphorin III/collapsin-1 in the
      adult rat and human brain: predominant expression in structures of the olfactory
      hippocampal pathway and the motor system.
AB  - Alterations in neuronal connectivity of the mature central nervous system (CNS)
      appear to depend on a delicate balance between growth-promoting and growth
      inhibiting molecules. To begin to address a potential role of the secreted
      chemorepulsive protein semaphorin(D)III/collapsin-1 (semaIII/coll-1) in
      structural plasticity during adulthood, we used high-resolution nonradioactive in
      situ hybridization to identify neural structures that express semaIII/coll-1 mRNA
      in the mature rat and human brain. SemaIII/coll-1 was expressed in distinct but
      anatomically and functionally linked structures of the adult nervous system. The
      olfactory-hippocampal pathway displayed semaIII/coll-1 expression in a continuum
      of neuronal structures, including mitral and tufted cells of the olfactory bulb,
      olfactory tubercle, and piriform cortex; and distinct nuclei of the amygdaloid
      complex, the superficial layers of the entorhinal cortex, and the subiculum of
      the hippocampal formation. In addition, prominent labeling was found in neuronal
      components of the motor system, particularly in cerebellar Purkinje cells and in
      subpopulations of cranial and spinal motoneurons. Retrograde tracing combined
      with in situ hybridization also revealed that the staining of semaIII/coll-1
      within the entorhinal cortex was present in the stellate neurons that project via
      the perforant path to the molecular layer of the dentate gyrus. Like in the rat,
      the human brain displayed discrete expression of semaIII/coll-1. Among the
      structures examined, the most prominent staining was observed in the cellular
      islands of the superficial layers of the human entorhinal cortex. The
      constitutive expression of the chemorepellent semaIII/coll-1 in discrete
      populations of neurons in the mature rat and human CNS raises the possibility
      that, in addition to its function as repulsive axon guidance cue during
      development, semaIII/coll-1 might be involved in restricting structural changes
      that occur in the wiring of the intact CNS.

PMID- 9556028
TI  - Polarized distribution and cell type-specific localization of telencephalin, an
      intercellular adhesion molecule.
AB  - Telencephalin is an intercellular adhesion molecule (ICAM) restricted to the
      telencephalon. This study demonstrates that immunolabeled telencephalin is
      targeted to the somatodendritic domain of cultured hippocampal pyramidal neurons
      beginning with the first stages of dendritic differentiation. In contrast, it is
      entirely excluded from all gamma-aminobutyric acid (GABA)ergic inhibitory
      interneurons at all stages of development. Prior to the stage at which nearly all
      pyramidal neurons express telencephalin, labeled neurons possess more extensive
      dendritic arbors than unlabeled pyramidal neurons. More synaptic boutons form
      with the larger, more elaborate telencephalin-expressing dendritic trees, but
      bouton number per unit length is similar between neurons with and without
      telencephalin. These findings suggest that telencephalin identifies pyramidal
      neurons, it may identify plasma membrane as dendritic, and it may be generally
      adhesive or stabilize dendritic membranes, but it is probably not specifically
      synaptic. Such characteristics would be expected to be important for the
      formation of cell type-specific dendritic arbors.

PMID- 9556029
TI  - Y1 receptors in the nucleus accumbens: ultrastructural localization and
      association with neuropeptide Y.
AB  - Neuropeptide Y (NPY) is present in aspiny neurons in the nucleus accumbens (NAc),
      which also contains moderate levels of ligand binding and mRNA for the Y1
      receptor. To determine the potential functional sites for receptor activation, we
      examined the electron microscopic immunocytochemical localization of antipeptide
      antisera against the Y1 receptor in the rat NAc. We also combined immunogold and
      immunoperoxidase labeling to show that, in this region, Y1 receptors are present
      in certain somatodendritic and axonal profiles that contain NPY or that appose
      NPY containing neurons. The Y1-like immunoreactivity (Y1-LI) was seen
      occasionally along plasma membranes but was associated more commonly with smooth
      endoplasmic reticulum (SER) and tubulovesicular organelles in somata and
      dendrites of spiny and aspiny neurons. The mean density of immunoreactive
      dendrites and spines per unit volume was greater in the "motor-associated" core
      than in the shell of the NAc. Y1-LI was also seen in morphologically heterogenous
      axon terminals, including those forming asymmetric excitatory-type synapses, and
      in selective astrocytic processes near this type of junction. We conclude that Y1
      receptors play a role in autoregulation of NPY-containing neurons but are also
      likely to be internalized along with endogenous NPY in NAc. Our results also
      implicate Y1 receptors in the NAc in post- and presynaptic effects of NPY and in
      glial functions involving excitatory neurotransmission. In addition, they suggest
      involvement of Y1 receptors in determining the output of a select population of
      neurons associated with motor control in the NAc core.

PMID- 9556030
TI  - Kainate-induced apoptosis correlates with c-Jun activation in cultured cerebellar
      granule cells.
AB  - We have investigated the involvement of c-Jun in cell death induced by exposure
      of primary cultures of murine cerebellar granule cells to the glutamate receptor
      agonist kainate (KA) and evaluated its possible use as a marker for apoptosis.
      Using cerebellar granule cell neurones from postnatal day 7 mice, we found that 1
      hr exposure to KA (1-1000 microM) induced a concentration-dependent neuronal cell
      death with characteristic apoptotic morphology, including cell shrinkage, neurite
      blebbing and DNA fragmentation. In addition KA-induced a concentration-dependent
      expression of c-Jun mRNA and protein as determined by in situ hybridization and
      immunocytochemistry respectively. DNA fragmentation was detected using terminal
      transferase-mediated nick-end (TUNEL) labelling and agarose gel electrophoresis.
      KA-induced cell death was significantly attenuated by the non-NMDA receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM), which shifted
      the concentration-response curve significantly rightward. The number of apoptotic
      cell bodies, determined by TUNEL, was also reduced by CNQX (50 microM), with only
      15-20% of neurones staining positive after exposure to 1mM KA. In addition, the
      number of positively stained cells for c-Jun protein and mRNA was substantially
      reduced by CNQX (50 microM) as determined by random and representative cell
      counts. These results show for the first time that KA induced apoptotic neuronal
      death in cultured murine cerebellar granule cells involves the induction of c-Jun
      mRNA and protein, suggesting the involvement of this immediate early gene in
      excitotoxic receptor-mediated apoptosis and its potential use as a marker for
      apoptotic cell death.

PMID- 9556031
TI  - Low affinity NGF receptor expression in the central nervous system during
      experimental allergic encephalomyelitis.
AB  - In the central nervous system (CNS), p75, or low-affinity nerve growth factor
      receptor (LNGFR), is assumed to play a critical role in mediating the effects of
      neurotrophins on neuronal survival. Recent studies have shown that nerve growth
      factor (NGF) can act also on immune cells through its binding to p75. Using
      immunohistochemistry, we have investigated the expression of the p75 receptor in
      the CNS during chronic relapsing experimental allergic encephalomyelitis (EAE) of
      the Lewis rat, an animal model of multiple sclerosis (MS). We report here a
      sequential expression of p75, first in Purkinje cells during the first attack,
      and secondly on both endothelial and perivascular cells in the latter stages of
      the disease. Moreover, starting from the second attack, p75 was also expressed on
      glial ensheathing cells, likely myelinating cells, located primarily in the
      dorsal roots. These data suggest that during EAE, LNGFR may play an important
      role in leukocyte-endothelial cell interactions and in the maintenance of
      Purkinje cells survival.

PMID- 9556032
TI  - NFAT interactions with the vasoactive intestinal peptide cytokine response
      element.
AB  - The vasoactive intestinal peptide cytokine response element (VIP CyRE) is
      responsible for mediating the transcriptional induction of the VIP gene to the
      neuropoietic cytokines leukemia inhibitory factor (LIF) and ciliary neurotrophic
      factor (CNTF). In investigating the sequence and function of the CyRE, we found a
      region of DNA with homology to the distal NFAT site in the IL-2 promoter. In this
      paper we characterize this sequence and show that the VIP NFAT site recognizes T
      cell NFAT with similar affinity to the previously characterized IL-2 NFAT site.
      However, despite its location in the middle of the CyRE, we find no CNTF/LIF
      induced binding to it. Instead we show that in NBFL neuroblastoma cells, the
      calcium ionophore A23187 induces a protein to bind to the VIP NFAT site. This
      A23187-mediated induction of nuclear protein binding to an NFAT oligonucleotide
      is dependent on extracellular calcium but not dependent on de novo protein
      synthesis. Thus, this protein has the characteristics of an NFAT-like protein and
      is recognized by an NFAT3-specific antiserum suggesting that it is indeed an NFAT
      protein. The location of the NFAT site in the VIP CyRE suggests that this may be
      one mechanism through which different signaling pathways engage in cross talk to
      alter VIP gene transcription.

PMID- 9556033
TI  - Selective outgrowth and differential tropism of amacrine and photoreceptor axons
      to cell targets during early development in vitro.
AB  - The axonal guidance and outgrowth in retinal neurons were investigated in
      cultures of pure retinal neurons (control) or in cocultures with heterologous
      BC3H-1 cells. Under control conditions, only about 10% of retinal neurons
      developed axons; coculturing with BC3H-1 cells induced early axonal outgrowth and
      guidance to BC3H-1 cells in most amacrine neurons. Both mechanisms were dependent
      on laminin and neural cell-adhesion molecules (N-CAMs) released by BC3H-1 cells,
      because they were prevented by antibodies directed against these molecules. The
      protein kinase C (PKC) inhibitor, staurosporine, reduced the effect of laminin on
      amacrine axonal outgrowth, suggesting that this effect was mediated by PKC. The
      occurrence of structures resembling synaptic boutons and the expression of
      synaptophysin at the amacrine axon ends of heterologous connections suggested
      that amacrine axons establish true synaptic contacts rather than simply
      overlapping with the BC3H-1 cells. In contrast to the heterologous contacts with
      BC3H-1 cells, the amacrine-amacrine axonal contacts observed in the cocultures
      were independent of laminin and N-CAM. Axonal outgrowth occurred in about 10% of
      the photoreceptors and was not affected by BC3H-1 cells or by substratum
      pretreatment with laminin or N-CAM. These results show that different mechanisms
      affect axonal outgrowth and guidance in amacrine and photoreceptor neurons in
      vitro, and they suggest that similar mechanisms could contribute to the
      development of the scaffold of axon pathways in the retina in vivo.

PMID- 9556034
TI  - RGS9: a regulator of G-protein signalling with specific expression in rat and
      mouse striatum.
AB  - A clone of the regulator of G-protein signalling, RGS9, was isolated from a rat
      striatum-minus-cerebellum-minus-hippocampus subtracted library generated by
      directional tag polymerase chain reaction subtraction. The full-length cDNA clone
      encodes a 444 amino acid protein containing an 118 amino acid RGS domain, which
      corresponds to an evolutionarily conserved domain that is present in all members
      of the RGS family of proteins. Outside of the homology domain, RGS9 shows more
      extended similarity to human RGS6 and RGS7, rat RGS12, and the C. elegans protein
      EGL-10. During embryonic and early postnatal stages of development, two RGS9
      transcripts of approximately 1.4 Kb and 1.8 Kb were detected in whole brain.
      After postnatal day 10, accumulation of the larger transcript increased
      progressively until adulthood at the expense of the smaller transcript, which was
      undetectable in the adult. In adult rat brain, the 1.8-Kb RGS9 transcript was
      detected in the striatum but not in other brain regions or peripheral tissues. In
      situ hybridization in rat and mouse demonstrates that RGS9 mRNA is expressed
      predominantly in medium-sized, spiny neurons of the neostriatum and in neurons of
      the nucleus accumbens and olfactory tubercle. Relatively strong signals were also
      detected in some hypothalamic nuclei. Its selective expression suggests that RGS9
      may play an important role in modulation of the complex signalling pathways of
      the basal ganglia.

PMID- 9556035
TI  - Trisomic zygote rescue revealed by DNA polymorphism analysis in confined
      placental mosaicism.
AB  - Uniparental disomy can be caused by different genetic mechanisms such as gamete
      complementation, chromosome duplication in monosomic zygote, or post-zygotic
      aneuploidy correction. This last mechanism is well documented in human
      reproduction and is related to placental mosaicism. In the case of a trisomic
      zygote which has originated by paternal or maternal non-disjunction at the first
      or second meiotic cell division, mosaicism will result from chromosome loss and
      restoration of a 'normalized' diploid fetal karyotype. In order to enrich the
      literature with new observations on this subject, we studied by DNA polymorphism
      analysis ten cases of confined placental mosaicism (CPM). The finding in
      placental DNA of three different alleles at polymorphic loci of chromosomes 13,
      16, and 20 demonstrated the trisomic status of the zygote in three cases. On the
      basis of these results, we believe that systematic DNA polymorphism analysis
      could give useful additional information to improve knowledge on aneuploidy
      correction in human reproduction.

PMID- 9556036
TI  - Reliable co-segregation analysis for prenatal diagnosis and heterozygote
      detection in Gaucher disease.
AB  - Mutations in the gene encoding beta-glucocerebrosidase are the main cause of
      Gaucher disease. The identification of some of these mutations in prenatal tests
      is a good complement to enzymatic assay and allows diagnosis and, in some cases,
      prognosis of the disease to be made. DNA analysis is particularly useful for
      carrier detection since the results of biochemical analyses are often ambiguous.
      The main drawback of mutation analysis for prenatal diagnosis and carrier
      detection in Gaucher disease is that rare mutations account for more than 30 per
      cent of the mutant alleles in most populations. The individual detection of these
      mutations is too expensive and time-consuming for routine use. Here we present a
      diagnostic protocol based on co-segregation analysis, using highly polymorphic
      markers, to be applied when at least one disease allele does not correspond to
      the most common mutations. Because of the frequency of the N370S mutation and its
      relevance for prognosis, an improved PCR detection method is included.

PMID- 9556037
TI  - Inhibin-B and pro-alphaC-containing inhibins in amniotic fluid from chromosomally
      normal and Down syndrome pregnancies.
AB  - In second-trimester Down syndrome pregnancies, levels of inhibin-A (the alpha
      betaA dimer) in maternal serum and amniotic fluid (AF) are significantly higher
      and lower than in normal pregnancy, respectively. Since AF also contains inhibin
      B (the alpha-betaB dimer) and precursor inhibins, we have examined whether the
      secretion of these inhibin isoforms may also be altered in association with Down
      syndrome. AF from 45 Down syndrome and 150 chromosomally normal pregnancies
      between 16 and 19 weeks' gestation were analysed, blinded to whether the sample
      was from a Down syndrome or a normal pregnancy. The median (10th-90th
      percentiles) inhibin-B level in the control pregnancies increased from 310.0
      (80.8-1112.5) pg/ml at 16 weeks to 459.5 (193.7-1386.8) pg/ml at 19 weeks'
      gestation. The corresponding figures for precursor inhibins (pro-alphaC inhibins)
      were 541.8 (206.9-1322.8) pg/ml at 16 weeks and 1391.8 (433.3-2652.6) pg/ml at 19
      weeks. Expressed as multiples of the median (MOM), the levels of inhibin-B and
      pro-alphaC inhibins in the Down syndrome samples were 0.85 and 0.79,
      respectively. Neither was significantly different from the controls. These data
      suggest that, of the three inhibin subunits, abnormal production or secretion of
      the inhibin betaA-subunit may underlie the decreased inhibin-A levels previously
      observed in Down syndrome. Confirmation of this by quantitative assessment of the
      inhibin subunit messenger ribonucleic acids would now be useful.

PMID- 9556038
TI  - Prenatal testing for genetic disorders among Arabs.
AB  - Since, at least in the near future, prenatal testing and abortion of affected
      fetuses will remain the main way of the prevention of genetic diseases, knowledge
      about the way of its acceptance in different cultures is important. The Israeli
      population includes two major groups: Jewish and Arabs, but while there is wide
      experience about the Jewish population and its attitude towards prenatal testing,
      little is known about the Arab population. This knowledge is particularly
      important, since genetic disorders are relatively frequent in the Arab world
      (Teebi and Farag, 1997). From 1992 to 1996, 816 prenatal tests were performed in
      our department on Arab women [143 chorionic villus sampling (CVS) procedures and
      673 amniocenteses]. The indication for an early prenatal test was a high risk for
      a monogenic disorder in 140 out of the 146 tests performed (143 CVS procedures
      and three early amniocenteses). In 26 cases, the fetus was found to be affected
      and early abortion was chosen by the couple in 25 cases (96 per cent). The 670
      late prenatal tests were done for various reasons including monogenic disorders
      (13 per cent), increased risk because of a previous child affected with Down
      syndrome or a neural tube defect (4.8 per cent), and an increased risk for a
      chromosomal aberration (78 per cent). In 31 cases of a late prenatal test, the
      fetus was found to be affected and only 21 couples (70 per cent) opted for an
      abortion. The major reason for this observation is probably related to religious
      and cultural factors. Since Arab women do not wish to have prenatal testing for
      only knowledge or reassurance, these factors should be taken into consideration
      during pre-amniocentesis counselling.

PMID- 9556039
TI  - The influence of smoking on maternal serum AFP and free beta hCG levels and the
      impact on screening for Down syndrome.
AB  - I have studied the impact of maternal smoking on the levels of maternal serum
      alpha-fetoprotein (AFP) and free beta human chorionic gonadotrophin (hCG) during
      the second trimester in a large series (30,727) of self-reported smokers and non
      smokers whose pregnancy resulted in the birth of a normal fetus. I have confirmed
      in a smaller subset of this population that self-reporting is an accurate method
      of assessing smoking status as confirmed by biochemical (serum cotinine)
      assessment. In addition, I have investigated marker levels among 195 pregnancies
      affected by Down syndrome with smoking status confirmed by measurement of serum
      cotinine. In both unaffected and Down syndrome groups, the incidence of smoking
      was 19 per cent but a considerable variation was observed with maternal age when
      the incidence in younger women (under 25) was 32 per cent. AFP median levels in
      unaffected smokers were 3 per cent higher, whilst in the Down syndrome group
      smoker medians were increased by 10 per cent compared with the non-smoker group.
      Free beta hCG levels in unaffected smokers were reduced by 14 per cent, whilst in
      the Down syndrome group smoker median levels were decreased by 16 per cent. In
      the smoker group, the Down syndrome detection rate was 10 per cent lower than in
      the non-smoker group, whilst the false-positive rate was also 2 per cent lower.
      Correcting for smoking status would redress this inequality and produce an
      overall 2 per cent increase in the detection rate for a 0.4 per cent increase in
      the false-positive rate. This increase in screening performance may be worth
      building into screening programmes, particularly in populations with a high
      smoking incidence.

PMID- 9556040
TI  - hCG and the free beta-subunit as screening tests for Down syndrome.
AB  - Published studies have reached varying conclusions as to the benefit of replacing
      human chorionic gonadotropin (hCG) measurements with the free beta-subunit of hCG
      (the free beta-subunit) for Down syndrome screening. One study reports 14 per
      cent higher detection for the free beta-subunit, while another finds an actual
      loss in detection. To explore this issue further, we directly compared the
      screening performance of hCG and the free beta-subunit, alone and in combination
      with other serum markers, using banked sera obtained prior to amniocentesis and
      karyotyping. Altogether, 52 Down syndrome and 5065 unaffected pregnancies were
      studied. Sera were thawed and assayed for hCG and the free beta-subunit over 1
      year. At a 5 per cent false-positive rate, the detection rate for hCG in
      combination with maternal age and alpha-fetoprotein was higher than when the free
      beta-subunit was substituted (62 versus 57 per cent). Ultrasound dating and
      adding unconjugated oestriol both increased detection. The present findings,
      along with those from six case control studies (our re-analysis), indicate that
      the screening performances of hCG and the free beta-subunit are similar (median
      change in detection 0, range -8 to +3 per cent). Under optimal sample collection
      and transportation conditions, laboratories can expect to achieve similar
      screening performance using either hCG or the free beta-subunit measurements.

PMID- 9556041
TI  - Prenatal diagnosis of fetal corpus callosum agenesis by ultrasonography and
      magnetic resonance imaging.
AB  - Corpus callosum agenesis (CCA) was evaluated by ultrasound examination and
      magnetic resonance imaging (MRI) in 14 cases. Ultrasonography was able to suspect
      CCA by indirect signs but a definitive diagnosis of CCA was achieved in only four
      cases. MRI was able to diagnose complete CCA in 13 cases and showed absence of
      the posterior portion of the corpus callosum in one case. Additional neurological
      abnormalities including heterotopia, gyration anomaly, asymmetry of the cerebral
      hemispheres, and Dandy-Walker variant were documented in five cases, as well as
      an ocular anomaly which was present in one case, by MRI examination. Prenatal
      counselling for fetal agenesis of the corpus callosum is difficult as the
      prognosis is uncertain. The association with other cerebral abnormalities
      increases the likelihood of a poor outcome and ultrasonographic assessment of the
      fetal brain is limited. We found MRI to be a safe and useful additional procedure
      to complement ultrasonographic diagnosis or suspicion of CCA.

PMID- 9556042
TI  - First 10,000 chorionic villus samplings performed on singleton pregnancies by a
      single operator.
AB  - Chorionic villus sampling (CVS) was performed in 10,000 consecutive singleton
      pregnancies by a single principal operator, working in two institutions. The
      procedure was performed between 8 and 32 gestational weeks: transabdominal (TA)
      sampling was carried out in 8479 cases and transcervical (TC) in 1521. Patients
      were referred for chromosomal risk in 89.1 per cent of cases, Mendelian disorders
      in 10.5 per cent, and DNA investigations for paternity or infectious agents in
      0.4 per cent of cases. The sampling success rate for both TA and TC techniques by
      the second insertion was 99.8 and 99.2 per cent, respectively. TA sampling
      succeeded in a higher number of cases at the first insertion (98 per cent vs.
      86.8 per cent) and was associated with smaller samples (< 10 mg) in fewer cases
      (3.2 per cent vs. 4.9 per cent). Cytogenetic analysis was highly successful (99.4
      per cent) and accurate; however, in one case a de novo structural rearrangement
      of chromosome I was not recognized. Mosaicism or rare trisomies were reported in
      1.30 per cent of cases. Five diagnostic errors in DNA investigation (0.51 per
      cent) ended with the birth of affected fetuses. Fetal loss through 28 weeks'
      gestation in the pregnancies intended to continue was 2.58 per cent; the rate
      increased with maternal age (1.22 per cent at less than 30 years to 3.8 per cent
      at 40 years or more), while gestational age affected the abortion rate only at 8
      weeks (odds ratio=2.22, P<0.05). Rates of premature delivery, low birth weight,
      and perinatal mortality did not differ from the Italian standards. By comparison
      with the Italian Birth Defects Registry data, no differences were found for the
      major malformations, including transverse limb reduction defects (TLRDs) (4.34
      vs. 3.28 x 10,000). Total malformations and TLRDs did not show any pattern
      relation to either maternal age or gestational age.

PMID- 9556043
TI  - Cardiac gene expression of GATA-4 transcription factor in human trisomy 21
      fetuses with increased nuchal translucency.
AB  - This study examines GATA-4 gene expression in cardiac tissue from fetuses with
      trisomy 21 presenting with increased nuchal translucency thickness at 10-14 weeks
      of gestation. mRNA was extracted from cardiac tissue after termination of
      pregnancy at 10-18 weeks of gestation in ten trisomy 21 fetuses and 29 normal
      controls. Northern and slot blots were performed and densitometric analysis of
      slot blots was used to determine the steady-state levels of expression of GATA-4.
      GATA-4 transcript levels were also compared with ANP and BNP, which have
      previously been measured in the same panel of samples. GATA-4 expression
      increased significantly with gestation but there was no significant difference
      between fetuses with trisomy 21 and controls. There was no significant
      association between GATA-4 expression and the steady-state level of transcripts
      for the natriuretic peptides.

PMID- 9556044
TI  - Attitudes towards abortion among physicians working at obstetrical and paediatric
      departments in Denmark.
AB  - The purpose of this study was to describe the attitudes among physicians working
      in perinatal medicine towards abortion for social reasons or because of abnormal
      prenatal diagnostic results. A questionnaire was sent to all physicians
      registered as employed at obstetrical or paediatric departments in Danish
      hospitals with a neonatal function. Of 994 questionnaires, 687 (69 per cent) were
      completed and returned. There was strong consensus among all participants that
      abortion is acceptable until week 21 in the case of trisomy 13 and at least until
      week 19 in the case of cystic fibrosis. Furthermore, there was strong consensus
      that abortion in the first trimester is acceptable in the case of an unwanted
      pregnancy in a 16-year-old girl and in the case of Down syndrome. Major
      controversy was found in connection with abortion in the case of Turner syndrome
      until week 21, abortion in week 13 in the case of polycystic kidney disease,
      abortion in week 24 in the case of Down syndrome, and abortion for social reasons
      in week 21.

PMID- 9556045
TI  - The distribution of nuchal translucency at 10-13 weeks of pregnancy.
AB  - There is a need for a simple method of expressing nuchal translucency measurement
      in early pregnancy that will allow for gestational age and be useful in screening
      for Down's syndrome. To achieve this objective, we conducted a prospective study
      of 561 women with singleton pregnancies that were not affected by Down's syndrome
      at 10-13 weeks of gestation. Nuchal translucency measurements and crown rump
      length measurements were determined. Nuchal translucency measurement increased by
      about 17 per cent per week. Expressing the result as a multiple of the median
      (MOM) nuchal translucency for a given crown rump length allowed for this increase
      with gestational age and yielded a distribution of values that was approximately
      Gaussian. About 96 per cent of values lay between 0.5 and 2.0 MOM. The variance
      and therefore the false-positive rate of nuchal translucency were significantly
      reduced by recording several measurements and using the average: for example, the
      false-positive rate reduced from 8.3 per cent to 5.0 per cent if the average of
      six measurements were used instead of one--a potential 40 per cent reduction in
      the false-positive rate if the test were used in screening. Estimating the
      distribution of nuchal translucency in MOM values will assist in specifying the
      statistical parameters to be used in prenatal screening for Down's syndrome and
      the use of repeated nuchal translucency measurements is expected to have a useful
      effect on reducing the screening false-positive rate at a given MOM cut-off
      level.

PMID- 9556046
TI  - Prenatal diagnosis of Menkes disease.

PMID- 9556047
TI  - Screening for Down syndrome at 14 weeks of pregnancy.
AB  - To investigate whether statistical parameters used in Down syndrome screening
      between 15 and 22 weeks of pregnancy can be used at 14 weeks, we assayed alpha
      fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic
      gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and inhibin-A in 16
      pregnancies with Down syndrome in the 14th week of pregnancy and expressed values
      in multiples of the normal median. The median and standard deviation values for
      these 16 pregnancies were not materially different from those published for 15-22
      weeks. It is reasonable, therefore, to offer Down syndrome screening using these
      markers starting at 14 completed weeks of pregnancy instead of 15 weeks. It needs
      to be recognized, however, that serum AFP measurement for neural tube defect
      screening is less effective at this time than between 16 and 18 weeks of
      pregnancy.

PMID- 9556048
TI  - Clinical management of a rare de novo translocation 46,X,t(Y;15) (p11.2
      approximately 11.3;q11.2).ish t(Y;15)(DYZ3+,AMELY+,SNRPN+;D15Z+) found
      prenatally.
AB  - A 40-year-old woman had amniocentesis at 16 weeks' gestation. Chromosome studies
      based on 15 colonies showed a de novo 46,X,t(Y;15)(p11.2 approximately
      11.3;q11.2) karyotype. Using C- and Q-banding, the additional material on 15
      appeared to be Yqh heterochromatin. The satellite on the small derivative
      chromosome was positive by AgNOR staining. Fluorescence in situ hybridization
      (FISH) studies using Y and 15 alpha satellite centromeric probes (DYZ3 and D15Z)
      showed that the derivative chromosome that resembled 15p+ had a Y centromere and
      that the satellited derivative had a 15 centromere. The break on Y was distal to
      the amelogenin locus and on 15 it was shown to be proximal to the Prader
      Willi/Angelman region by using the SNRPN probe. DNA studies ruled out uniparental
      disomy of chromosome 15 and a SRY deletion. The pregnancy was continued and a
      normal baby boy without any discernible abnormalities was born.

PMID- 9556049
TI  - Application of the surface rendering technique of three-dimensional ultrasound in
      prenatal diagnosis and counselling of Klippel-Trenaunay-Weber syndrome.
AB  - Klippel Trenaunay-Weber syndrome is a complex developmental disorder
      characterized by a triad of cutaneous haemangioma, varicosities of the body, and
      unilateral limb hypertrophy. We describe the prenatal diagnosis of Klippel
      Trenaunay-Weber syndrome at 15 weeks' gestation using the surface rendering
      technique of three-dimensional ultrasound. The vivid three-dimensional images of
      the affected fetus are invaluable in prenatal diagnosis and parental counselling.

PMID- 9556050
TI  - Re: 'Single umbilical artery--right or left? Does it matter?' by Blazer et al.

PMID- 9556051
TI  - Mental status and psychosocial functioning in XYY males.

PMID- 9556052
TI  - Transient unilateral cerebral ventriculomegaly.

PMID- 9556053
TI  - Bone and the hematopoietic and immune systems: a report of the proceedings of a
      scientific workshop.
AB  - Recent observations underscore the linkage between endochondral bone formation
      and the establishment of hematopoietic marrow and suggest that interactions among
      bone, marrow, and the immune system persist in the mature skeleton. A workshop
      was held at the National Institutes of Health, Bethesda, Maryland, to discuss
      recent work on these interactions and to identify new areas of research. Marrow
      stromal cells include the precursors of the osteochondrogenic lineage, exert
      important influences on osteoclastogenesis and lymphopoiesis, and mediate the
      effects of some systemic factors on bone turnover. Recent evidence indicates that
      hematopoietic cells can influence the differentiation of osteogenic cells and
      suggests that mature lymphocytes can influence osteoclastic and osteoblastic
      functions. However, interpretation of experiments may be confounded by the
      potential for stage-specific responses within a cell lineage, the likelihood that
      divergent pathways compete for limited pools of precursor cells, and the
      possibility that important cells or factors are still unidentified. Further, in
      vitro models may be limited by species and anatomical site specificities, the
      absence of intermediary or accessory cells, and the absence of normal marrow
      spatial organization and cellular interactions with the extracellular matrix.
      Nevertheless, current approaches hold the potential for significant advances in
      our understanding of the relationships between bone and the hematopoietic and
      immune systems. Refinements of in vitro systems, the use of genetically
      manipulated mice, and the examination of clinical syndromes promise important
      insights. Collaborations among bone biologists, hematologists, and immunologists,
      and between basic scientists and clinical investigators, will be crucial for
      continued progress.

PMID- 9556054
TI  - Seasonal deficiency of vitamin D in children: a potential target for osteoporosis
      preventing strategies?
AB  - Peak bone mass attained after skeletal growth is a major determinant of the risk
      of developing osteoporosis later in life, hence the importance of nutritional
      factors that contribute to bone mass gain during infancy and adolescence. An
      adequate supply of vitamin D is essential for normal bone homeostasis. This study
      was undertaken to determine what the levels are of 25-hydroxyvitamin D (25(OH)D)
      that may be considered desirable in children and to assess if normal children
      maintain these levels throughout the year. Vitamin D metabolites and parathyroid
      hormone (PTH) serum levels were measured in 21 children in March and October,
      prior to and after the administration of a daily supplement of 25(OH)D (40 microg
      for 7 consecutive days). There were inverse correlations between basal 25(OH)D
      levels and supplementation-induced changes in serum 1,25(OH)2D (r = 0.57, p <
      0.05) and PTH (r = 0.41, p < 0.05). When basal levels of 25(OH)D were below 20
      ng/ml, the supplement induced an increase in serum 1,25(OH)2D; with basal 25(OH)D
      under 10-12 ng/ml, the supplement also decreased serum PTH. The lowest serum
      level of 25(OH)D in 43 normal children studied in summer was 13 ng/ml. Those
      results suggested that the lowest limit for desirable levels of 25(OH)D in
      children was somewhere between 12 and 20 ng/ml. However, 31% of 51 normal
      children studied in winter had levels below 12 ng/ml, and 80% had levels lower
      than 20 ng/ml. Those children are likely to have suboptimal bioavailability of
      vitamin D, which might hamper their achievement of an adequate peak bone mass.
      Since cutaneous synthesis of vitamin D is rather limited in winter, oral vitamin
      D supplementation should be considered.

PMID- 9556055
TI  - The biological activity of nonsteroidal vitamin D hormone analogs lacking both
      the C- and D-rings.
AB  - 1alpha,25-dihydroxyvitamin D is a key calcium-regulating hormone but also
      displays potent differentiating and antiproliferative activities on many cell
      types. The structural requirements of this secosteroid hormone have been
      extensively studied for the A-ring and side chain, whereas relatively little is
      known about the requirements of the natural CD-ring structure for the vitamin D
      like biological activity. We have embarked on a vast program in which derivatives
      were synthesized and evaluated characterized by profound structural changes in
      the central C/D-region. This first series of nonsteroidal analogs consists of
      (1R,3S)-5-((Z,2E)-4-((1S,3S)-3-(4-hydroxy-4-methylpentyl)-1,2,2-++
      +trimethylcyclopentyl)-2-butenylidene)-4-methylenecyclohexan e-1,3-diol (KS 176)
      and derivatives thereof. These analogs are characterized by the absence of normal
      C- and D-rings and by the presence of an unnatural five-membered ring which we
      call the E-ring. KS 176 with the otherwise natural side chain structure of
      1alpha,25(OH)2D3 has between 10 and 30% of the biological activity of
      1alpha,25(OH)2D3 when tested in vitro (prodifferentiating effects on HL-60 and MG
      63; antiproliferating activity on MCF-7 and keratinocytes) but has minimal in
      vivo calcemic effects. Introduction of several side chain modifications created
      analogs with increased intrinsic noncalcemic biological properties, whereas their
      calcemic potency remains very low. These data demonstrate that the full CD-rings
      are not mandatory for the biological activity of 1alpha,25(OH)2D3 since they can
      be replaced by a new ring structure which generates an appropriate spacing of the
      A-seco B-rings in relation to the side chain. The biological activity of these
      nonsteroidal analogs probably involves a classical genomic activation since they
      are also active in transfection assays using an osteocalcin vitamin D responsive
      element coupled to a human growth hormone reporter gene.

PMID- 9556056
TI  - 1,25(OH)2D3 regulates protein kinase C activity through two phospholipid
      dependent pathways involving phospholipase A2 and phospholipase C in growth zone
      chondrocytes.
AB  - We have previously shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a
      major role in growth zone chondrocyte (GC) differentiation and that this effect
      is mediated by protein kinase C (PKC). The aim of the present study was to
      identify the signal transduction pathway used by 1,25(OH)2D3 to stimulate PKC
      activation. Confluent, fourth passage GC cells from costochondral cartilage were
      used to evaluate the mechanism of PKC activation. Treatment of GC cultures with
      1,25(OH)2D3 elicited a dose-dependent increase in both inositol-1,4,5
      trisphosphate and diacylglycerol (DAG) production, suggesting a role for
      phospholipase C and potentially for phospholipase D. Addition of
      dioctanoylglycerol to plasma membranes isolated from GCs increased PKC activity.
      Neither pertussis toxin nor choleratoxin had an inhibitory effect on PKC activity
      in control or 1,25(OH)2D3-treated GCs, indicating that neither Gi nor Gs proteins
      were involved. Phospholipase A2 inhibitors, quinacrine, OEPC (selective for
      secretory phospholipase A2), and AACOCF3 (selective for cytosolic phospholipase
      A2), and the cyclooxygenase inhibitor indomethacin decreased PKC activity, while
      the phospholipase A2 activators melittin and mastoparan increased PKC activity in
      GC cultures. Arachidonic acid and prostaglandin E2, two downstream products of
      phospholipase A2 action, also increased PKC activity. These results indicate that
      1,25(OH)2D3-dependent stimulation of PKC activity is regulated by two distinct
      phospholipase-dependent mechanisms: production of DAG, primarily via
      phospholipase C and production of arachidonic acid via phospholipase A2.

PMID- 9556057
TI  - Coupling of calcium receptors to inositol phosphate and cyclic AMP generation in
      mammalian cells and Xenopus laevis oocytes and immunodetection of receptor
      protein by region-specific antipeptide antisera.
AB  - Ca2+ and other divalent cations modulate parathyroid hormone secretion by
      interacting with cell-surface Ca2+-sensing receptors (CaRs). We assessed the
      ability of these receptors to couple to Ca2+ mobilization, inositol phosphate
      (InsP) accumulation, and cyclic AMP production in different expression systems.
      In Xenopus laevis oocytes injected with bovine parathyroid CaR cRNA, the addition
      of extracellular cations to 1.5 mM Ca2+, 5.5 mM Mg2+, or 10 microM Gd3+
      significantly increased 45Ca efflux (p < 0.01). InsP accumulation also increased
      dramatically when adding these cations to human embryonic kidney (HEK) 293 cells
      stably transfected with wild-type bovine parathyroid CaR cDNA. Raising the
      extracellular [Ca2+] ([Ca2+]o) from 0.1 to > 1.4 mM in oocytes and to > 1.0 mM in
      HEK 293 cells stimulated significant increments in 45Ca efflux and InsP
      accumulation, respectively (p < 0.05). In contrast, Ca2+ and Mg2+ increased InsPs
      to a lesser extent in COS 7 cells transiently transfected with CaR cDNA. In HEK
      293 cells stably expressing CaR cDNA, there were significant reductions in cAMP
      content when adding high Ca2+, Mg2+, Gd3+, or the CaR modulator NPS R-467. Three
      region-specific anti-CaR peptide antisera immunoblotted bands of approximately
      140 and 155 kDa in membranes from CaR-transfected HEK 293 cells and bovine
      parathyroid tissue. Immunocytochemistry demonstrated strong cell-surface staining
      in CaR-transfected HEK 293 cells and parathyroid tissue, which was absent when
      antisera were preabsorbed with CaR peptides. These results indicate that the
      activation of the recombinant CaR by extracellular Ca2+ can couple negatively to
      adenylate cyclase but positively to phospholipase C (PLC), the latter at
      physiological [Ca2+]o.

PMID- 9556058
TI  - Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent
      post-translational prenylation of GTP-binding proteins, including Ras.
AB  - Bisphosphonates are currently the most important class of antiresorptive drugs
      used for the treatment of metabolic bone diseases. Although the molecular targets
      of bisphosphonates have not been identified, these compounds inhibit bone
      resorption by mechanisms that can lead to osteoclast apoptosis. Bisphosphonates
      also induce apoptosis in mouse J774 macrophages in vitro, probably by the same
      mechanisms that lead to osteoclast apoptosis. We have found that, in J774
      macrophages, nitrogen-containing bisphosphonates (such as alendronate,
      ibandronate, and risedronate) inhibit post-translational modification
      (prenylation) of proteins, including the GTP-binding protein Ras, with farnesyl
      or geranylgeranyl isoprenoid groups. Clodronate did not inhibit protein
      prenylation. Mevastatin, an inhibitor of 3-hydroxy-3-methylglutatyl (HMG)-CoA
      reductase and hence the biosynthetic pathway required for the production of
      farnesyl pyrophosphate and geranylgeranyl pyrophosphate, also caused apoptosis in
      J774 macrophages and murine osteoclasts in vitro. Furthermore, alendronate
      induced apoptosis, like mevastatin-induced apoptosis, could be suppressed in J774
      cells by the addition of farnesyl pyrophosphate or geranylgeranyl pyrophosphate,
      while the effect of alendronate on osteoclast number and bone resorption in
      murine calvariae in vitro could be overcome by the addition of mevalonic acid.
      These observations suggest that nitrogen-containing bisphosphonate drugs cause
      apoptosis following inhibition of post-translational prenylation of proteins such
      as Ras. It is likely that these potent antiresorptive bisphosphonates also
      inhibit bone resorption by preventing protein prenylation in osteoclasts and that
      enzymes of the mevalonate pathway or prenyl protein transferases are the
      molecular targets of the nitrogen-containing bisphosphonates. Furthermore, the
      data support the view that clodronate acts by a different mechanism.

PMID- 9556059
TI  - Na+ -phosphate cotransport in mouse distal convoluted tubule cells: evidence for
      Glvr-1 and Ram-1 gene expression.
AB  - While there is considerable evidence for phosphate (Pi) reabsorption in the
      distal tubule, Pi transport and its regulation have not been well characterized
      in this segment of the nephron. In the present study, we examined Na+-dependent
      Pi transport in immortalized mouse distal convoluted tubule (MDCT) cells. Pi
      uptake by MDCT cells is Na+-dependent and, under initial rate conditions, is
      inhibited by phosphonoformic acid (41 +/- 3% of control), a competitive inhibitor
      of Na+-Pi cotransport. The transport system has a high affinity for Pi (Km = 0.46
      mM) and is stimulated by lowering the extracellular pH from 7.4 to 6.4 and
      inhibited by raising the pH from 7.4 to 8.4. Exposure to Pi-free medium for 21 h
      increased Na+-Pi cotransport from 2.1 to 5.5 nmol/mg of protein/5 minutes (p <
      0.05) while parathyroid hormone, forskolin, and phorbol 12-myristate 13-acetate
      failed to alter Pi uptake in MDCT cells. Reverse transcriptase polymerase chain
      reaction of MDCT cell RNA provided evidence for the expression of the Npt1 but
      not the Npt2 Na+-Pi cotransporter gene. However, preincubation of MDCT cells with
      Npt1 antisense oligonucleotide led to only 20% inhibition of Na+-Pi cotransport,
      suggesting that other Na+-Pi cotransporters are operative in MDCT cells. Indeed,
      we showed, by ribonuclease protection assay, that MDCT cells express the
      ubiquitous cell surface receptors for gibbon ape leukemia virus (Glvr-1) and
      amphoteric murine retrovirus (Ram-1) that also function as Na+-Pi cotransporters.
      In summary, we demonstrate that the pH dependence and regulation of Na+-Pi
      cotransport in MDCT cells is distinct from that in the proximal tubule and
      suggest that different gene products mediate Na+-Pi cotransport in the proximal
      and distal segments of the nephron.

PMID- 9556060
TI  - Immortalization and characterization of bone marrow stromal fibroblasts from a
      patient with a loss of function mutation in the estrogen receptor-alpha gene.
AB  - A male patient with abnormal postpubertal bone elongation was shown earlier to
      have a mutation in both alleles of the estrogen receptor, resulting in a
      nonfunctional gene. Marrow stromal fibroblasts (MSFs) derived from this patient
      were called HERKOs (human estrogen receptor knock outs), and in order to obtain
      continuous HERKO cell lines, they were immortalized using a recombinant
      adenovirus-origin-minus SV40 virus. MSFs are unique cells because they support
      hematopoesis and contain a mixed population of precursor cells for bone,
      cartilage, and fat. Three established cell lines (HERKO2, HERKO4, and HERKO7)
      were characterized and compared with the heterogeneous population of
      nonimmortalized HERKOs for their osteogenic potential. We performed Northern
      analysis of matrix genes implicated in bone development and metabolism and an in
      vivo bone formation assay by transplanting the cells subcutaneously into
      immunodeficient mice. All three HERKO lines expressed high amounts of collagen
      1A1, osteopontin, osteonectin, fibronectin, decorin, biglycan, and alkaline
      phosphatase. Except for osteopontin, expression of these genes was slightly lower
      compared with nonimmortalized HERKOs. In the in vivo bone formation assay, the
      heterogeneous population of nonimmortalized HERKOs formed bone with high
      efficiency, while the HERKO lines induced a high-density, bone-like matrix.
      Finally, all HERKO cell types secreted high levels of insulin-like growth factor
      I and interleukin-6 into the culture medium relative to cells of normal human
      subjects. In summary, these lines of HERKO cells retain several of the phenotypic
      traits of MSFs after immortalization, including matrix and cytokine production,
      and provide a valuable source of a unique human material for future studies
      involving estrogen action in bone and bone marrow metabolism.

PMID- 9556061
TI  - Reciprocal temporospatial patterns of Msx2 and Osteocalcin gene expression during
      murine odontogenesis.
AB  - Msx2 is a homeodomain transcription factor that regulates craniofacial
      development in vivo and osteocalcin (Osc) promoter activity in vitro. Msx2 is
      expressed in many craniofacial structures prior to embryonic day (E) E14 but is
      expressed at later stages in a restricted pattern, primarily in developing teeth
      and the calvarium. We examine Osc expression by in situ hybridization during
      murine development, detailing temporospatial relationships with Msx2 expression
      during preappositional and appositional odontogenesis and calvarial osteogenesis.
      Osc expression at E14-14.5 is very low, limited to a few perichondrial
      osteoblasts in the dorsal aspect of developing ribs. At E16.5 and E18.5, Osc
      expression is much higher, widely expressed in skeletal osteoblasts, including
      calvarial osteoblasts that do not express Msx2. No Osc is detected in early
      preappositional teeth that express Msx2. In incisors studied at an early
      appositional phase, Msx2 is widely expressed in the tooth, primarily in ovoid
      preodontoblasts and subjacent dental papilla cells. Osc is detected only in a
      small number of maturing odontoblasts that also express alpha1(I) collagen
      (Colla1) and that are postproliferative (do not express histone H4). Msx2
      expression greatly overlaps both histone H4 and Colla1 expression in ovoid
      preodontoblasts and dental papilla cells. By the late appositional phases of
      E18.5 and neonatal teeth, Osc mRNA is highly expressed in mature columnar
      odontoblasts adjacent to accumulating dentin. In appositional bell-stage molars,
      reciprocal patterns of Msx2 and Osc are observed in adjacent preodontoblasts and
      odontoblasts within the same tooth. Osc is expressed in mature columnar
      odontoblasts, while Msx2 is expressed in adjacent immature ovoid preodontoblasts.
      In less mature teeth populated only by immature ovoid preodontoblasts, only Msx2
      is expressed-no Osc is detected. Thus, Msx2 and Osc are expressed in reciprocal
      patterns during craniofacial development in vivo, and Msx2 expression in
      preodontoblasts clearly precedes Osc expression in odontoblasts. In functional
      studies using MC3T3-E1 calvarial osteoblasts, Msx2 suppresses endogenous Osc, but
      not osteopontin, mRNA accumulation. In toto, these data suggest that Msr2
      suppresses Osc expression in the craniofacial skeleton at stages immediately
      preceding odontoblast and osteoblast terminal differentiation.

PMID- 9556062
TI  - Spatiotemporal assessment of fetal bovine osteoblast culture differentiation
      indicates a role for BSP in promoting differentiation.
AB  - Fetal bovine mandible-derived osteoblasts were cultured for the purpose of
      obtaining a spatiotemporal assessment of bone matrix protein expression during in
      vitro differentiation. The results obtained from electron microscopic,
      immunohistological, biochemical, and molecular biological analyses indicated that
      these primary cultured osteoblasts produce an abundant extracellular matrix which
      mineralizes during a 14-day culture period. During this process, a restricted,
      spatiotemporal pattern of bone sialoprotein expression was indicated by
      immunohistological and molecular evaluations. To test the possibility that bone
      sialoprotein promoted the continued morphodifferentiation of osteoblastic cells,
      cultures were grown in the presence of anti-bone sialoprotein antibodies known to
      interfere with cell-bone sialoprotein attachment. Compared with cultures grown in
      the presence of normal rabbit serum (1:150), cultures grown in the media
      containing anti-bone sialoprotein antibody (1:150) failed to mineralize as
      demonstrated by von Kossa staining and failed to express osteocalcin and
      osteopontin as shown by the reverse transcription polymerase chain reaction.
      These results contribute to the growing evidence that bone sialoprotein is an
      important determinant of osteoblast differentiation and bone formation. Matrix
      protein-cell interactions may be examined using this spatiotemporally defined
      model.

PMID- 9556063
TI  - Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2
      induced osteogenic differentiation.
AB  - Direct cell-cell interactions are fundamental for tissue development and
      differentiation. We have studied the expression and function of cadherins in
      human osteoblasts during in vitro differentiation. Using reverse transcription
      polymerase chain reaction and mRNA hybridization, we found that human trabecular
      bone osteoblasts (HOBs), osteoprogenitor marrow stromal cells (BMCs), and the
      osteogenic sarcoma lines, SaOS-2 and MG-63, expressed mRNA for cadherin-11 (C11)
      and N-cadherin (N-cad). HOBs and BMCs also expressed low levels of cadherin-4
      (C4) mRNA. C11 was the most abundant cadherin protein present in human
      osteoblasts, and its expression was unaffected by bone morphogenetic protein-2
      (BMP-2) treatment of either BMCs or HOBs. Likewise, N-cad mRNA did not change
      during BMP-2 incubation. Conversely, C4 protein, undetectable in transformed cell
      lines, was down-regulated by BMP-2 treatment of normal cells. Both C11 and C4
      were localized to sites of cell-cell contact in both HOBs and BMCs, colocalized
      with beta-catenin, and bands corresponding to cadherins were coimmunoprecipitated
      by a beta-catenin antibody, findings indicative of functional cadherins. A
      decapeptide containing the HAV motif of human N-cad partially inhibited Ca2+
      dependent cell-cell adhesion and completely prevented BMP-2-induced stimulation
      of alkaline phosphatase activity by BMCs. Thus, human osteoblasts and their
      progenitor cells express a repertoire of multiple cadherins. Cadherin-mediated
      cell-to-cell adhesion is critical for normal human osteoblast differentiation.

PMID- 9556064
TI  - The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic
      cells are differentiation stage specific.
AB  - Fibroblast growth factors (FGFs) appear to play an important role in human
      cranial osteogenesis. We therefore investigated the effects of recombinant human
      FGF-2 (rhFGF-2) on human calvaria (HC) osteoblastic cells. Immunocytochemical
      analysis showed that confluent HC cells express both FGF receptors -1 and -2. In
      short-term culture, rhFGF-2 (0.1-100 ng/ml, 2-5 days) increased HC cell growth
      and decreased alkaline phosphatase (ALP) activity and type I collagen (ColI)
      synthesis, as evaluated by P1CP levels. When HC cells were induced to
      differentiate in long-term culture in the presence of 50 microg/ml ascorbic acid
      and 3 mM phosphate, HC cells initially proliferated, then ALP activity and ColI
      synthesis decreased and calcium content in the extracellular matrix increased.
      Continuous treatment with rhFGF-2 (50 ng/ml) for 1-28 days, or a transient rhFGF
      2 treatment for 1-7 days, slightly increased DNA synthesis at 7 days, whereas a
      late treatment for 8-28 days had no effect on cell growth. The continuous and
      transient treatments with rhFGF-2 decreased ALP activity, ColI synthesis, and
      matrix mineralization. This was associated with a transient fall in osteocalcin
      (OC) production at 7 days. In contrast, the late rhFGF-2 treatment for 8-28 days
      only slightly inhibited ALP activity and increased matrix mineralization. In
      addition, both continuous and late treatments with rhFGF-2 increased OC
      production in more mature cells at 3-4 weeks of culture. We also found that the
      early and late treatments with rhFGF-2 had opposite effects on transforming
      growth factor beta2 production in proliferating cells and more mature cells. The
      results show that rhFGF-2 slightly stimulates cell growth and reduces the
      expression of osteoblast markers in less mature cells, whereas it induces OC
      production and matrix mineralization in more mature cells, indicating that the
      effects of FGF-2 are differentiation stage specific and that FGF-2 may modulate
      HC osteogenesis by acting at distinct stages of cell maturation.

PMID- 9556065
TI  - Mesenchymal stem cell surface antigen SB-10 corresponds to activated leukocyte
      cell adhesion molecule and is involved in osteogenic differentiation.
AB  - Bone marrow contains a rare population of mesenchymal stem cells (MSCs) capable
      of giving rise to multiple mesodermal tissues including bone, cartilage, tendon,
      muscle, and fat. The cell surface antigen recognized by monoclonal antibody SB-10
      is expressed on human MSCs but is lost during their developmental progression
      into differentiated phenotypes. Here we report on the immunopurification of the
      SB-10 antigen and its identification as activated leukocyte-cell adhesion
      molecule (ALCAM). Mass spectrometry establishes that the molecular mass of ALCAM
      is 80,303 +/- 193 Da and that it possesses 17,763 +/- 237 Da of N-linked
      oligosaccharide substituents. Molecular cloning of a full-length cDNA from a MSC
      expression library demonstrates nucleotide sequence identity with ALCAM. We also
      identified ALCAM homologs in rat, rabbit, and canine MSCs, each of which is over
      90% identical to human ALCAM in their peptide sequence. The addition of antibody
      SB-10 Fab fragments to human MSCs undergoing osteogenic differentiation in vitro
      accelerated the process, thereby implicating a role for ALCAM during bone
      morphogenesis and adding ALCAM to the group of cell adhesion molecules involved
      in osteogenesis. Together, these results provide evidence that ALCAM plays a
      critical role in the differentiation of mesenchymal tissues in multiple species
      across the phylogenetic tree.

PMID- 9556066
TI  - Role of interleukin-6 in uncoupling of bone in vivo in a human squamous carcinoma
      coproducing parathyroid hormone-related peptide and interleukin-6.
AB  - OCC tumor has been established from a human squamous carcinoma associated with
      humoral hypercalcemia of malignancy (HHM) and shown to overproduce parathyroid
      hormone-related peptide (PTHrP) and cause aggressive hypercalcemia when implanted
      into nude rats. In the present study, we have demonstrated by reverse
      transcription-polymerase chain reaction and Northern blot analysis that OCC tumor
      also overexpressed interleukin 6 (IL-6) mRNA and that tumor-bearing animals
      exhibited a marked increase in plasma IL-6 as well as PTHrP concentrations. When
      a monoclonal antibody against human IL-6 was injected to block the activities of
      tumor-derived IL-6, bone loss in tumor-bearing animals was significantly
      prevented. Quantitative bone histomorphometric analysis revealed that treatment
      with anti-IL-6 antibody caused a substantial decrease in both osteoclast number
      and eroded surface (as parameters of bone resorption) and also a significant
      increase in the mineral apposition rate, but little effect on the osteoblastic
      surface. These results provide in vivo evidence suggesting that in tumors
      coproducing IL-6 and PTHrP, IL-6 is involved not only in the acceleration of
      osteoclastic bone resorption but also, at least in part, in the suppression of
      osteoblastic functions in HHM syndrome.

PMID- 9556067
TI  - Cathepsin K mRNA detection is restricted to osteoclasts during fetal mouse
      development.
AB  - We recently identified a novel cysteine protease, cathepsin K, by random
      sequencing of an osteoclast cDNA library, and in situ hybridization studies in
      adult human tissues demonstrated high and specific expression in osteoclasts. To
      determine whether the expression of cathepsin K mRNA during mouse embryogenesis
      was more widespread, cryostat sections of early (day 11-13) and late (day 15-17)
      mouse fetuses were analyzed by in situ hybridization. Serial cross-sections were
      collected through each fetus, and co-reacted for tartrate-resistant acid
      phosphatase (TRAP) and nonspecific esterase (NSE), selective markers for the
      osteoclast, and precursor cells derived from the macrophage/monocyte lineage,
      respectively. In the 11-13 day fetuses, cathepsin K mRNA was not expressed in any
      extraskeletal tissue; at this stage of embryogenesis, no osteoclasts are present.
      However, in the 15-17 day fetuses, a distinctive, developmental stage-dependent
      pattern of cathepsin K expression was observed in osteoclasts and preosteoclasts
      at sites of cartilage and bone modeling. Cathepsin K positive osteoclasts
      differentiated within a peripheral zone of the osteogenic stacked cell layer of
      the cartilage rudiments (prior to ossification), migrated and/or resorbed the
      bone collar, and invaded the cartilage core. Furthermore, following the invasive
      penetration of vasculature into the degenerating cartilage core, the calcified
      cartilage was resorbed by cathepsin K positive mononuclear osteoclast precursors
      (NSE+ve, negligible TRAP); cells positive for both enzymes were identified
      indicative of osteoclast differentiation. The deposition of bone by osteoblasts
      onto the cartilage remnants is followed by mononucleated and multinucleated
      osteoclastic resorption; these osteoclasts demonstrated intense cathepsin K
      expression. Similar expression patterns were observed at sites of intramembranous
      ossification. No expression was observed in chondrocytes, osteoblasts, marrow, or
      in any other nonskeletal tissue at these time points. These data indicated that
      cathepsin K expression during embryogenesis occurred only following the onset of
      osteoclast differentiation.

PMID- 9556068
TI  - Characterization of serum tartrate-resistant acid phosphatase and development of
      a direct two-site immunoassay.
AB  - Osteoclasts secrete tartrate-resistant acid phosphatase (TRAP) to the
      circulation, where the amount of TRAP is expected to correlate with the bone
      resorption rate. We have developed two monoclonal antibodies, O1A and J1B, using
      purified human bone TRAP as antigen. The antibodies recognized different
      epitopes, allowing us to develop a two-site fluoroimmunoassay. The
      immunoreactivity in fresh serum specimens was less than 10% of the concentrations
      measured from the same specimens after 24 h of storage at 4 degrees C, or after
      addition of 5 mM EDTA or EGTA to them. When fresh serum was gel filtrated using
      Sephacryl S-200 column, all of the enzyme eluted in the void volume as a complex
      with a molecular weight of more than 250 kDa. If the serum was treated with EDTA
      before the gel filtration, the complex was destroyed and the enzyme eluted in
      fractions corresponding to a molecular weight of 30 kDa, the size of monomeric
      purified human bone TRAP. The immunoassay was used to measure TRAP concentrations
      from serum samples that had been stored at 4 degrees C for 24 h. According to the
      assay, premenopausal women had 13.1 +/- 3.1, postmenopausal women 17.6 +/- 4.2,
      and children 32.6 +/- 12.2 microg TRAP/l of serum. We conclude that TRAP
      circulates in the serum as part of a complex, which also contains Ca2+, and that
      TRAP-immunoassay is a potentially useful method for determining bone resorption
      rates, as long as the complex is destroyed before the assay.

PMID- 9556069
TI  - Wortmannin inhibits spreading and chemotaxis of rat osteoclasts in vitro.
AB  - Wortmannin (WT) and 17beta-hydroxywortmannin (HWT), which are inhibitors of
      phosphatidylinositol-3(OH)-kinase (PI3K), have been shown previously to inhibit
      bone resorption in vitro and in vivo, possibly by interfering with formation of
      the osteoclast ruffled border. Since migration of osteoclasts also plays an
      important role in the process of bone resorption, we investigated the effects of
      these inhibitors on osteoclast morphology and motility. Both HWT and WT caused a
      sustained decrease in the planar area of osteoclasts in vitro (half maximal
      effect at 25 and 165 nM, respectively), with the effect of HWT on cell area more
      readily reversible than WT. These agents also caused accumulation of
      intracellular vesicles. Time-lapse video microscopy was used to record the
      migration of osteoclasts in response to macrophage colony-stimulating factor (M
      CSF) or vehicle, flowing passively from a micropipette positioned 200-400 microm
      from the cell. M-CSF caused directed migration of osteoclasts, indicating
      chemotaxis (over 3 h osteoclasts migrated 96 +/- 14 microm in response to M-CSF
      vs. 11 +/- 2 microm in control experiments). Both WT (100 or 500 nM) and LY294002
      (100 microM), a specific PI3K inhibitor structurally unrelated to WT,
      significantly inhibited osteoclast chemotaxis in response to M-CSF. Taken
      together, these effects of WT, HWT, and LY294002 are consistent with an important
      role for PI3K in regulating cytoskeletal function in osteoclasts. The inhibitory
      effects of WT and HWT on bone resorption may be due, in part, to impairment of
      osteoclast motility.

PMID- 9556070
TI  - Bone mineral density and its change in white women: estrogen and vitamin D
      receptor genotypes and their interaction.
AB  - Low bone mineral density (BMD) is a major risk factor for development of
      osteoporosis; increasing evidence suggests that attainment and maintenance of
      peak bone mass as well as bone turnover and bone loss have strong genetic
      determinants. We examined the association of BMD levels and their change over a 3
      year period, and polymorphisms of the estrogen receptor (ER), vitamin D receptor
      (VDR), type I collagen, osteonectin, osteopontin, and osteocalcin genes in pre-
      and perimenopausal women who were part of the Michigan Bone Health Study, a
      population-based longitudinal study of BMD. Body composition measurements,
      reproductive hormone profiles, bone-related serum protein measurements, and life
      style characteristics were also available on each woman. Based on evaluation of
      women, ER genotypes (identified by PvuII [n = 253] and XbaI [n = 248]) were
      significantly predictive of both lumbar spine (p < 0.05) and total body BMD
      level, but not their change over the 3-year period examined. The VDR BsmI
      restriction fragment length polymorphism was not associated with baseline BMD,
      change in BMD over time, or any of the bone-related serum and body composition
      measurements in the 372 women in whom it was evaluated. Likewise, none of the
      other polymorphic markers was associated with BMD measurements. However, we
      identified a significant gene x gene interaction effect (p < 0.05) for the VDR
      locus and PvuII (p < 0.005) and XbaI (p < 0.05) polymorphisms, which impacted BMD
      levels. Women who had the (-/-) PvuII ER and bb VDR genotype combination had a
      very high average BMD, while individuals with the (-/-) PvuII ER and BB VDR
      genotype had significantly lower BMD levels. This contrast was not explained by
      differences in serum levels of osteocalcin, parathyroid hormone, 1,25
      dihydroxyvitamin D, or 25-dihydroxyvitamin D. These data suggest that genetic
      variation at the ER locus, singly and in relation to the vitamin D receptor gene,
      influences attainment and maintenance of peak bone mass in younger women, which
      in turn may render some individuals more susceptible to osteoporosis than others.

PMID- 9556071
TI  - Systemic over-secretion of growth hormone in transgenic mice results in a
      specific pattern of skeletal modeling and adaptation.
AB  - The effects of growth hormone (GH) over-secretion on bone modeling and remodeling
      in transgenic mice were investigated using systematic and hierarchical methods.
      The results showed that continual systemic stimulation of GH over-secretion in
      mice resulted in an initial increase in bone mass, but its bone quality was not
      comparable with that of the littermate controls. Further continual over
      stimulation of GH resulted in an increase in bone resorption leading to thinner
      cortices with inferior tissue mechanical properties. Three biological mechanisms
      following GH over-production are formulated to explain the observed results: GH
      over-secretion stimulated the production of inferior bone matrices, i.e., woven
      bone and cartilage, in addition to the production of normal lamellar bone; the
      increased bone formation stimulated by GH was followed by an exaggerated bone
      resorption process, resulting in cortical tissue with inferior mechanical
      properties; and a cortical shift occurred following GH over-stimulation that
      appeared to be caused by the combined effects of GH over-secretion and a
      variation in mechanical stimuli in the metallothionein-1 growth hormone
      regulating hormone transgenic mice. An "Optimal Strain Environment" model is
      proposed to help explain the observed results. From the results of the present
      and previous studies, we believe that the primary goal of bone adaptation to a
      biological perturbation, at least in mice, is to ensure proper mechanical
      function by maintaining structural integrity. In the process of maintaining a
      targeted whole bone structural integrity, the mechanical integrity of tissue may
      be sacrificed.

PMID- 9556072
TI  - Concentration of transforming growth factor beta in human bone tissue:
      relationship to age, menopause, bone turnover, and bone volume.
AB  - Transforming growth factor beta (TGF-beta) is thought to play an important role
      in bone metabolism, but its relationship to human bone turnover and bone mass has
      not been examined yet. In this study, we measured the concentration of TGF-beta
      in 811 samples of male and female bone from four representative sites of the
      human skeleton and in the supernatants of 72 short-term human bone marrow
      cultures from the iliac crest. The concentrations of TGF-beta1 and TGF-beta2 in
      the bone matrix were positively correlated with histomorphometric indices of bone
      resorption and bone formation and with serum levels of osteocalcin and bone
      specific alkaline phosphatase. We also observed a positive association between
      the release of TGF-beta in the bone marrow cultures and serum osteocalcin.
      Changes in the rate of cancellous or cortical bone remodeling with age or
      menopause were accompanied by corresponding changes in skeletal TGF-beta. In
      contrast, there was no significant relationship between the concentration of TGF
      beta and bone volume at any skeletal site. In conclusion, our study supports the
      hypothesis that TGF-beta plays an important role in human bone remodeling, but
      fails to demonstrate an association between the skeletal concentration of TGF
      beta and human bone mass.

PMID- 9556073
TI  - Human growth hormone locally released in bone sites by calcium-phosphate
      biomaterial stimulates ceramic bone substitution without systemic effects: a
      rabbit study.
AB  - Calcium-phosphate bone replacement biomaterial has been used as a drug carrier
      for therapeutic agents. This study investigated the efficacy of local
      administration of human growth hormone (hGH) by macroporous biphasic calcium
      phosphate (MBCP) implants in improving the bone substitution qualities of
      ceramics. hGH release from MBCP implants loaded with 1 microg of hGH was rapid
      during the first 48 h and then sustained for a total of 9 days.
      Immunolocalization of hGH in vitro and in vivo by transmission electron
      microscopy showed its presence inside the material, indicating that it was able
      to penetrate within the porosity of the ceramic during the adsorption process.
      MBCP cylinders (6 x 6 mm) were loaded with 0.1, 1, and 10 microg of hGH and
      implanted into rabbit femurs (n = 40). The effects of locally released hGH on
      bone ingrowth and ceramic resorption were evaluated by scanning electron
      microscopy and image analysis. The results indicated that hGH increased bone
      ingrowth (+65%) and ceramic resorption (+140%) significantly in comparison with
      control implants and that the increase was dose dependent. Biochemical parameters
      monitored in rabbit plasma and urine, as well as the absence of any significant
      difference between contralateral implants and the control, indicated that hGH did
      not produce detectable systemic effects. Thus, the use of MBCP appears to be
      effective for local delivery of hGH, resulting in improved bone substitution.

PMID- 9556074
TI  - Magnesium deficiency: a cause of heterogeneous disease in humans.

PMID- 9556075
TI  - Bone alkaline phosphatase during short-term treatment with insulin-like growth
      factor I and growth hormone in growth hormone-deficient adults.

PMID- 9556076
TI  - Angiotensin receptors and norepinephrine neuromodulation: implications of
      functional coupling.
AB  - The objective of this review is to examine the role of neuronal angiotensin II
      (Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have
      been identified in cardiovascularly relevant areas of the brain: the AT1 and the
      AT2. We have utilized neurons in culture to study the signaling mechanisms of AT1
      and AT2 receptors. Neuronal AT1 receptors are involved in norepinephrine (NE)
      neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE
      neuromodulation involves AT1 receptor-mediated, losartan-dependent, rapid NE
      release, inhibition of K+ channels and stimulation of Ca2+ channels. AT1 receptor
      mediated enhanced NE neuromodulation involves the Ras-Raf-MAP kinase cascade and
      ultimately leads to an increase in NE transporter, tyrosine hydroxylase and
      dopamine beta-hydroxylase mRNA transcription. Neuronal AT2 receptors signal via a
      Gi protein and are coupled to activation of PP2A and PLA2 and stimulation of K+
      channels. Finally, putative cross-talk pathways between AT1 and AT2 receptors
      will be discussed.

PMID- 9556077
TI  - Characterization and localization of galanin receptors in human entorhinal
      cortex.
AB  - The neuropeptide galanin (GAL) has a widespread distribution throughout the human
      cortex. The entorhinal cortex (ENT) plays a crucial role in the transfer of
      cortico-cortical information related to memory and displays severe degeneration
      in Alzheimer's disease (AD). However, very little is known about the pharmacology
      of the GAL receptor (GALR) in normal human ENT. Therefore, we pharmacologically
      visualized their distribution and characterized GALRs using in vitro receptor
      autoradiography and radioligand binding assays. Autoradiograms revealed intense
      GALR labeling, mainly in the substantia innominata, hypothalamus, the bed nucleus
      of the stria terminalis and within layers 2 and 4 of the ENT. Kinetic experiments
      showed that saturation of GALR sites by [125I]GAL (human) (hGAL) occurred within
      2 h and that this binding readily reversed in the presence of a GTP analog, but
      not in the presence of excess unlabeled hGAL. Analysis of [125I]hGAL binding data
      from saturation experiments gave KD values of 98.6+/-21.6 pM, Bmax values of
      52.9+/-32.4 fmol/mg protein and identified a high and low affinity state of the
      GALR. The presence of 5'-guanylylimidodiphosphate (GppNHp) or NaCl reduced the
      agonist labeling of hGALR in ENT membranes.

PMID- 9556078
TI  - Bioactivity of intraduodenally and intravenously infused fragments of luminal
      cholecystokinin releasing factor (LCRF).
AB  - A luminal cholecystokinin releasing factor (LCRF), has been purified from
      intestinal secretion and found to have a mass of 8136 daltons. The amino-terminal
      41 residues have been sequenced. Previous studies showed that intraduodenal
      infusion of the synthetic amino-terminal 35 amino acid peptide, LCRF1-35
      significantly stimulated pancreatic protein and fluid secretion in conscious
      rats, but the peptide did not stimulate amylase release from isolated, dispersed
      pancreatic acini. In the present study, several fragments of LCRF were
      synthesized and tested for CCK-releasing activity (pancreatic protein secretion)
      to determine whether shorter fragments of LCRF exhibit the characteristic
      biological activity of native LCRF and synthetic LCRF1-35. Compounds tested were
      LCRF1-41, LCRF1-35, LCRF1-65 and LCRF11-25. Of the fragments shorter than LCRF1
      35, only LCRF11-25 but not LCRF1-6 had significant CCK releasing activity. LCRF1
      41 was equivalent to LCRF1-35 in potency and efficacy. Intravenous and
      intraduodenal infusion of LCRF1-35 elicited nearly identical dose-response
      curves.

PMID- 9556079
TI  - Uroguanylin: gene structure, expression, processing as a peptide hormone, and co
      storage with somatostatin in gastrointestinal D-cells.
AB  - Guanylin/GCAP-I and uroguanylin/GCAP-II are two structurally related peptides
      which play an important role in the regulation of water/electrolyte balance
      within the gut. In order to enable the investigation and comparison of both
      peptide hormones at the genomic level, we decided to clone the corresponding
      genes. The human gene for guanylin/GCAP-I and its 5'-flanking region have been
      described recently. Here, we report the three exon/two intron structure of the
      human uroguanylin/GCAP-II gene and its localization on chromosome 1 p35-34, as
      determined by radiation hybrid mapping. Together with data obtained for the
      guanylin/GCAP-I gene we show that these genes are localized in the same
      chromosomal area with other guanlyl cyclase-activating peptides like ANP etc.
      Northern hybridization revealed that the expression of the uroguanylin/GCAP-II
      gene is highest in the intestinal mucosa, especially in the ileum and colon. By
      means of polymerase chain reaction (PCR), an expression was also observed in the
      stomach where no guanylin/GCAP-I expression is detectable. Using
      immunohistochemical methods, uroguanylin/GCAP-II immunoreactive material was
      distinctly localized in D-type gastric and intestinal endocrine cells. Although
      the comparable data on the genomic organisation of both peptide hormones verify
      their high degree of relationship, this finding indicates a special task of
      uroguanylin/GCAP-II within the stomach, such as regulatory functions in gastric
      secretion. The redundant expression of the GCAP/GC-C system in the small and
      large intestine, however, is as yet unclear.

PMID- 9556080
TI  - Evidence that peroral calcium does not activate the gastrin-ECL-cell axis in the
      rat.
AB  - The ECL cells are histamine- and pancreastatin-secreting endocrine cells in the
      oxyntic mucosa, thought to release a blood Ca2+-lowering peptide hormone upon
      stimulation by gastrin. Previously, we have shown that the ECL cells do not
      respond to perturbations in blood Ca2+. In the present study, we examine if Ca2+
      in the gastric lumen will affect the activity of the gastrin-ECL-cell axis.
      Freely fed or food deprived (48 h) rats were given an oral load of CaCl2 (or
      NaCl), and the blood Ca2+ concentration was monitored. The serum gastrin
      concentration at sacrifice, 3 h after ingestion of CaCl2, was measured together
      with two parameters of ECL cell activity: the oxyntic mucosal histidine
      decarboxylase (HDC) activity and the serum pancreastatin concentration. The
      circulating concentrations of calcitonin and parathyroid hormone (PTH) were also
      measured. Oral CaCl2 raised the blood Ca2+ in a dose-dependent manner. The two
      highest doses (which caused damage to the oxyntic mucosa) raised the serum
      gastrin concentration and the HDC activity in both fed and fasted rats; the serum
      pancreastatin concentration remained unaffected. Oral CaCl2 raised the serum
      calcitonin concentration and lowered the serum PTH concentration. The effects of
      high doses of oral CaCl2 on the serum gastrin concentration and on the oxyntic
      mucosal HDC activity could be reproduced by a high dose of NaCl. Thus the effects
      are probably not due to Ca2+ per se. We conclude that the gastrin-ECL-cell axis
      in the rat does not respond to peroral Ca2+. Since the ECL cells do not respond
      to either circulating or peroral Ca2+ they are unlikely to secrete a calciotropic
      hormone.

PMID- 9556081
TI  - Autoradiographic identification of a gastrin receptor on the human parietal cell.
AB  - Gastrin plays an important role in regulating gastric acid secretion and
      gastrointestinal mucosal growth but its cellular sites of action in man have not
      been determined. Using cryostat sections of gastric mucosal tissue we have
      identified (125I-gastrin binding followed by fixation-wet emulsion
      autoradiography) and characterized (125I-gastrin binding followed by counting) a
      gastrin receptor binding site in the human stomach. This site displayed binding
      characteristics similar to those observed in isolated cell systems: specifically,
      125I-gastrin binding was rapid (t1/2 approximately 10 min at 37 degrees C),
      temperature-dependent (3.5 fold more radioligand bound at 22 degrees C than at 4
      degrees C) and saturable. The binding of the radioligand was also tissue specific
      and was five-fold greater in the gastric body than in the gastric antrum and
      duodenum. In the autoradiographs, silver grains were localized only to parietal
      cells and not to other epithelial cell types. In the presence of 40 nM gastrin
      grains were no longer present over parietal cells demonstrating that these sites
      were both saturable and of high affinity. These data provide the first
      demonstration of gastrin binding sites (putative receptors) on parietal cells in
      the human stomach and suggest that gastrin acts directly on these cells to help
      regulate gastric acid secretion and/or mucosal growth.

PMID- 9556082
TI  - Fetal pulmonary immunoreactive adrenocorticotropin: molecular weight and cellular
      localization.
AB  - The hypothalamus-pituitary-adrenal axis of the sheep fetus plays a critical role
      in fetal development, responsiveness to stress, and initiation of parturition. We
      have recently reported that the fetal lung contains and secretes significant
      amounts of immunoreactive adrenocorticotropin (iACTH). The present study was
      designed to identify the molecular weight profile and the cellular location of
      iACTH in this tissue. iACTH extracted from fetal lung was immunoprecipitated,
      electrophoresed, and immunoblotted. Pulmonary iACTH was found in several
      molecular forms. The largest peptides appeared as doublets, and had molecular
      weights similar to POMC (32, 33 kD). Smaller peptides appeared in molecular
      weights (17, 24, and 27 kD) which were not consistent with the post-translational
      processing of POMC in fetal pituitary, but which were consistent with known
      processing of POMC by chromaffin granule aspartyl protease. None of the molecular
      forms of iACTH were glycosylated. Immunohistochemistry revealed that the iACTH
      was contained within bronchial epithelium and within groups of cells within the
      parenchyma of the lung. Both of these types of cells are consistent with
      pulmonary neuroendocrine cells. The distribution of neuroendocrine cells and
      apparent concordance with the iACTH-positive cells was confirmed by
      immunostaining for neuron specific enolase, a marker for neuroendocrine cells
      within the lung. We conclude that the lung contains unprocessed and partially
      processed POMC within cells known to contain neuropeptides. We speculate that
      secretion of the POMC-related peptides from these cells is physiologically
      important in the late-gestation fetus.

PMID- 9556083
TI  - Chromatographic and immunological identification of GnRH (gonadotropin-releasing
      hormone) variants. Occurrence of mammalian and a salmon-like GnRH in the
      forebrain of an eutherian mammal: Hydrochaeris hydrochaeris (Mammalia, Rodentia).
AB  - The molecular variants of Gonadotropin releasing hormone (GnRH) in brain extracts
      of the eutherian mammal Hydrochaeris hydrochaeris (Mammalia, Rodentia) were
      characterized. An indirect method combining reverse-phase high-performance liquid
      chromatography (RP-HPLC) and radioimmunoassay (RIA) with different antisera was
      used. Two different forebrain regions (olfactory bulbs and preoptic-hypothalamic
      region) were analyzed. Characterization of RP-HPLC fractions from preoptic
      hypothalamic extracts with three different RIA systems revealed two
      immunoreactive GnRH (ir-GnRH) peaks coeluting with mammalian GnRH (mGnRH) and
      salmon GnRH (sGnRH) synthetic standards. These results were additionally
      supported by serial dilution studies with specific antisera. Similar results were
      obtained from olfactory bulb extracts with the same methodology. However, a third
      ir-GnRH peak in a similar position to that of chicken GnRH II (cIIGnRH) synthetic
      standard was revealed. As far as we know, this is the first report showing
      chromatographic and immunological evidences for the presence of a second GnRH
      variant in the forebrain of an eutherian mammal.

PMID- 9556084
TI  - Scientific and ethical issues of preimplantation diagnosis.
AB  - Preimplantation diagnosis (PID) offers couples at high risk of having offspring
      affected with a genetic disorder the possibility of an early prenatal diagnosis.
      For many couples this approach will give the opportunity to avoid a selective
      termination of affected pregnancies. Substantial advances were made in PID since
      the report, in 1990, of the first birth obtained after PID. Yet, many technical
      hazards have to be solved for PID to become a standard clinical tool. The very
      close correlation existing between the forthcoming developments in the fields of
      PID and human genome mapping will improve the reliability and efficiency of
      genetic diagnosis. In the near future, the procedure may also become easier and
      safer. As a consequence, the indications for PID could be extended to other
      genetic defects, such as multifactorial diseases. They could also be extended to
      cases with no medical background, such as social gender selection or behavioural
      traits. In this perspective, it is now time for both the medical and scientific
      communities to identify the ethical issues related to these potential new
      indications.

PMID- 9556085
TI  - Hormonal regulation of appetite and food intake.
AB  - Several clinical disorders are strongly influenced by hormones involved in
      appetite and weight regulation. Obesity and eating disorders are of major
      importance, because they are associated with severe morbidity and considered to
      be among the greatest health problems in the Western world today. This review
      describes recent findings in hormonal regulation of food intake by substances
      acting both centrally, such as corticotropin-releasing factor, neuropeptide Y and
      leptin, and peripherally, such as cholecystokinin and somatostatin. Sex hormones
      and glucocorticoids play an important role in long-term regulation of metabolism.
      The role of these hormones in appetite and weight changes during life as well as
      during pregnancy and lactation is discussed. Furthermore, the development of
      obesity and eating disorders is influenced, in particular, by steroid hormones.
      Treatment with sex hormones, as in hormone replacement therapy, affects appetite
      and weight and may have beneficial effects in preventing android obesity.
      Currently, there is great effort in developing endogenous neurohumoral substances
      into effective drugs for the treatment of obesity and eating disorders. Leptin
      and neuropeptide Y analogues are of interest as potential antiobesity agents.

PMID- 9556086
TI  - Fetal alcohol syndrome: a Japanese perspective.
AB  - To estimate and prevent the effects of prenatal alcohol on the central nervous
      system (CNS), brain dysfunction in fetal alcohol syndrome (FAS) and fetal alcohol
      effects (FAE) was compared by both epidemiological and experimental studies. The
      FAS infants exhibited a more severe degree of CNS involvement than the FAE
      infants. The CNS involvement features were developmental delay and intellectual
      impairment in both FAS and FAE. The increased risk of low birth weight and CNS
      involvement were much more significant in women who were heavy drinkers or
      alcoholics and smoked. The beneficial effect of supplementary zinc on the fetal
      cerebrum of FAS or FAE rats was limited, never reaching the unexposed control
      level. One of the most vulnerable structures in the rat fetus exposed to ethanol
      in utero was the synaptic formation in the hippocampus. The consistent
      dysmorphogenesis of synapses during early brain development may be associated
      with the functional impairment of the CNS in FAS and FAE.

PMID- 9556087
TI  - Chlamydia pneumoniae and its role in chronic obstructive pulmonary disease.
AB  - The diverging of T-helper (Th) cells into predominantly Th1 and Th2 subsets on
      the basis of their cytokine profiles has decisively improved our understanding of
      the pathogenesis of many chronic infectious diseases. Recent data suggest that
      the presence of interferon-gamma and the subsequent suppression of interleukin-4
      production leads to a Th1-type response that is required for the resolution of
      infections caused by intracellular pathogens. The ability of the macrophages to
      respond aggressively during early antigen contact seems to be one crucial factor
      in the development of an appropriate Th-cell response. Several host-related
      factors can affect macrophage function and the polarization of T-cell responses,
      ie the shift from a Th1 response to a Th2 one, and thus dramatically deteriorate
      the resolution of infections caused by intracellular agents such as Chlamydia
      pneumoniae. Chronic C. pneumoniae infection has been associated with several
      common chronic diseases, quite recently with chronic obstructive pulmonary
      disease. Chronic C. pneumoniae infection may amplify smoking-associated
      inflammation in the bronchi and may be a contributory factor in the development
      of irreversible pathological changes.

PMID- 9556088
TI  - Idiopathic thrombocytopenic purpura: a guideline for diagnosis and management of
      children and adults. American Society of Hematology.
AB  - Idiopathic thrombocytopenic purpura (ITP, also known as immune thrombocytopenic
      purpura) affects both children and adults. In childhood, the peak age is 2-4
      years, girls and boys are equally affected, and in most children, the disease is
      self-limited with spontaneous recovery occurring in several weeks to several
      months. In adults, ITP is most common among young women, and the disease is more
      insidious in its onset and chronic in its course. In both children and adults,
      there are important unresolved issues in diagnosis and management that have major
      cost implications. For this reason, the American Society of Hematology chose ITP
      as the disease topic for its initial practice guideline in 1993. In 1996, the
      practice guideline was published in Blood, the Journal of the American Society of
      Hematology. This review describes the principle features of ITP in children and
      adults, the process of development of the practice guideline for ITP, and the
      implications of the guideline for the diagnosis and management of patients with
      ITP.

PMID- 9556089
TI  - Paediatric kidney transplantation.
AB  - Renal transplantation is the optimal form of renal replacement therapy leading to
      substantial improvement in the quality of life. It has rapidly become the
      standard treatment for end-stage renal disease in children. However, despite
      impressive short-term results significant long-term problems remain unsolved.
      Because of the lack of effective treatment for chronic rejection and common
      recipient noncompliance, allograft half-life has not improved significantly
      during the last decade. A paediatric recipient is likely to need several
      retransplantations in adulthood. Moreover, the immunosuppressive drugs used today
      have potentially serious side-effects including nephrotoxicity and de novo
      malignancy. These are especially relevant for paediatric recipients who will
      continue to receive therapy for several decades. Most therapeutic protocols used
      for children are derived from those used for adults. However, the metabolic
      differences between an adult and a growing and developing paediatric transplant
      recipient are not always adequately appreciated before these new therapies are
      initiated. In the near future, we are likely to see new and more efficient drugs
      become available. It is important that we try to understand their properties in
      children and use them and our current arsenal on an individual basis aiming at
      optimal graft survival but also at avoiding unnecessary adverse effects.

PMID- 9556090
TI  - Genetics, molecular mechanisms and management of long QT syndrome.
AB  - Cardiac arrhythmias cause more than 300,000 sudden deaths each year in the USA
      alone. Long QT syndrome (LQT) is a cardiac disorder that causes sudden death from
      ventricular tachyarrhythmias, specifically torsade de pointes. Four LQT genes
      have been identified: KVLQT1 (LQT1) on chromosome 11p15.5, HERG (LQT2) on
      chromosome 7q35-36, SCN5A (LQT3) on chromosome 3p21-24, and MinK (LQT5) on
      chromosome 21q22. SCN5A encodes the cardiac sodium channel, and LQT-causing
      mutations in SCN5A lead to the generation of a late phase of inactivation
      resistant whole-cell inward currents. Mexiletine, a sodium channel blocker, is
      effective in shortening the QT interval corrected for heart rate (QTc) of
      patients with SCN5A mutations. HERG encodes the cardiac I(Kr) potassium channel.
      Mutations in HERG act by a dominant-negative mechanism or by a loss-of-function
      mechanism. Raising the serum potassium concentration can increase outward HERG
      potassium current and is effective in shortening the QTc of patients with HERG
      mutations. KVLQT1 is a cardiac potassium channel protein that interacts with
      another small potassium channel MinK to form the cardiac I(Ks) potassium channel.
      Like HERG mutations, mutations in KVLQT1 and MinK can act by a dominant-negative
      mechanism or a loss-of-function mechanism. An effective treatment for LQT
      patients with KVLQT1 or MinK mutations is expected to be developed based on the
      functional characterization of the I(Ks) potassium channel. Genetic testing is
      now available for some patients with LQT.

PMID- 9556091
TI  - Hirschsprung's disease genes and the development of the enteric nervous system.
AB  - Hirschsprung's disease or aganglionic megacolon causes chronic, congenital
      obstipation at an incidence of 1 per 5000 live births. Two approaches have been
      vital to the present understanding of the pathogenesis and genetic background of
      the disease: disease linkage analyses and mouse models of aganglionic megacolon.
      Because the increasing number of transgenic or natural mouse strains with
      congenital megacolon has led to mutation screening in Hirschsprung's disease
      patients, almost every second patient could now receive a genetic explanation for
      his/her disease. The known disease genes include tyrosine kinase receptor Ret,
      endothelin receptor B and its ligand endothelin 3. In addition, mutations have
      been found in the gene encoding the glial cell line-derived neurotrophic factor,
      the ligand for Ret, but these may only have a modifier effect. The mouse models
      have also provided insight into the developmental mechanisms of the normal
      intestinal innervation. We combine here the present clinical data on the gene
      mutations in Hirschsprung's disease with the experimental molecular biology data,
      and formulate a hypothesis on the pathogenesis of this multigenic-multifactorial
      disease.

PMID- 9556092
TI  - Prognosis of colorectal cancer varies in different high-risk conditions.
AB  - Variation in prognosis between different colorectal cancer (CRC) patient groups
      was studied by comparing the survival rates of patients belonging to three cancer
      predisposition groups with those with sporadic CRC. The high-risk groups included
      43 members of hereditary nonpolyposis colorectal cancer (HNPCC) families, 25
      patients with familial adenomatous polyposis (FAP) and 33 patients with
      underlying ulcerative colitis (UC). The control group included 122 consecutive
      sporadic CRC patients. Cumulative 5-year survival was highest in HNPCC (86%),
      which is significantly better than in sporadic colorectal cancer (59%, hazard
      ratio 0.41, P = 0.02). Cancer associated with UC had a 5-year survival rate of
      39%, which is significantly less than in sporadic cancer (hazard ratio 1.83, P =
      0.03). There was no significant difference in the survival between patients with
      FAP and patients with sporadic CRC (hazard ratio 1.27, P = 0.5). Exclusion of
      cases detected by screening examinations slightly reduced the survival rates; 85%
      for HNPCC, 53% for FAP and 28% for UC. However, the differences between the
      groups remained significant. The survival of patients with HNPCC was found to be
      better than that among other groups in this study, which probably relates to the
      specific tumourigenesis involving DNA mismatch repair dysfunction.

PMID- 9556093
TI  - Melatonin: marvel or marker?
AB  - Melatonin blanches the skin of frogs, whitens the fur of hamsters, and sometimes
      makes the gonads atrophy. It is remarkable that such a hormone would be put
      forward as a defense against ageing. We have been examining excretion of the
      urinary metabolite of melatonin, 6-sulphatoxymelatonin (6-SMT), in 150
      postmenopausal women, in 72 volunteers over the age of 60 years who complained of
      insomnia or depression, and in 20 healthy younger adult controls, aged 18-40
      years. The acrophase or fitted peak of 6-SMT excretion was computed as a marker
      of the timing of the circadian system. Total daily excretion of 6-SMT was not
      significantly related to total sleep time, wake-within-sleep or sleep complaints.
      Nevertheless, whereas the 20 controls displayed a normal range of 6-SMT
      acrophases from 01.32 to 05.44 h, 42% of the postmenopausal women and 48% of the
      symptomatic elders had acrophases outside this normal range. Those volunteers
      with more deviant acrophases displayed more disturbed sleep and more sleep
      complaints. These data suggest that melatonin is a useful marker of circadian
      rhythm phase disorders, but suggest a need for more caution in melatonin
      administration.

PMID- 9556094
TI  - Melatonin receptor genes.
AB  - Melatonin is produced rhythmically by the pineal gland and the retina with
      increased synthesis during darkness. Pineal melatonin serves as the 'chemical
      expression of darkness' conveying information on the ambient light-dark cycle
      into rhythmic bodily functions. On-going debate on modes and sites of action
      ranges from views of melatonin affecting each and every cell ('cure-all') to
      those of melatonin having restricted actions through specific high-affinity
      receptors. The present review deals with the latter view. The use of 2-[125I]
      iodomelatonin has allowed the exact localization and characterization of high
      affinity melatonin receptors that signal through the G(i/o) class of G proteins.
      Molecular cloning of melatonin receptor genes has confirmed that most, if not
      all, high-affinity melatonin-binding sites represent the G-protein-coupled
      melatonin receptors. Based on sequence dissimilarities, melatonin receptors are
      classified into three subtypes, Mel1a, Mel1b and Mel1c. A distribution wider than
      originally thought of melatonin receptors in the human brain and peripheral sites
      has brought these receptors into focus of several drug companies, promising
      exciting times for research on melatonin and new therapeutic possibilities.

PMID- 9556095
TI  - Integrating the actions of melatonin on human physiology.
AB  - Melatonin has a diverse range of physiological effects in humans. Reported
      effects include modulation of the sleep-wake, thermoregulatory, cognitive,
      cardiovascular and immune systems. While integrating these broad-ranging effects
      is difficult when current paradigms are used, the diverse effects of melatonin on
      human physiology may be better understood by shifting our theoretical
      perspective. Traditionally, research has treated melatonin as a classical hormone
      for which a defined effect in physiological systems and a mechanism of action can
      be elucidated. In this article, we suggest that it may be more appropriate to
      view melatonin as an evolutionally stable timing signal to which each species has
      adapted the timing of physiological processes. From this perspective, it appears
      that the physiological role of melatonin in humans falls into two categories. The
      first relates to the self-regulation of circadian timing by the suprachiasmatic
      nucleus-pineal complex. The second relates to the promotion of restorative or
      anabolic physiological processes. In humans, elevated melatonin levels have been
      associated with reduced core temperature, increased heat loss, decreased
      cardiovascular output, reduced alertness and enhanced immune responsiveness.
      Taken together, these changes suggest that melatonin may increase the propensity
      for physiological processes promoting nocturnal sleep or processes that occur
      during the sleep period.

PMID- 9556096
TI  - Melatonin and human reproduction.
AB  - In photoperiodic nonhuman mammals the secretion of melatonin from the pineal
      gland plays a major role in regulating reproductive physiology; in humans these
      relationships are less clear. The melatonin rhythm changes throughout life with
      the first substantial change in nocturnal melatonin secretion being reportedly
      associated with puberty. The transition from Tanner stage 1 to Tanner stage 5 of
      sexual maturation is associated with a significant reduction in nocturnal
      melatonin levels, but a cause-effect relationship has not been established.
      Menstrual cyclicity has been reported to be associated with fluctuations in
      melatonin production but whether they are related to, eg ovulation or
      menstruation is not established. At high latitudes the quantity of melatonin
      produced by the pineal gland varies with season (changes in the light-dark
      cycle), and there is some evidence that this changes reproductive efficiency
      accordingly. Menopause is associated with a reduction in melatonin which may
      relate to the changing gonadotropin levels. In males of the same age melatonin
      levels also drop with no significant alteration in reproductive physiology. While
      correlations between melatonin and the status of the reproductive system in
      humans have been noted, whether they are functionally related remains to be
      determined.

PMID- 9556097
TI  - Melatonin--the key to the gate of sleep.
AB  - This article reviews the evidence that melatonin, a hormone produced by the
      pineal gland during the dark hours, plays a major role in the regulation of the
      sleep-wake cycle. In recent years, our laboratory has been involved in a large
      scale project aimed at investigating the role of endogenous melatonin in sleep
      wake regulation and the effects of nonpharmacological levels of melatonin on
      sleep. Based on our finding on the precise coupling between the endogenous
      nocturnal increase in melatonin secretion and the opening of the nocturnal sleep
      gate, we propose that the role of melatonin in the induction of sleep does not
      involve the active induction of sleep, but is rather mediated by an inhibition of
      a wakefulness-producing mechanism in the central nervous system. Our studies also
      suggest that exogenously administered melatonin may be beneficial in certain
      types of insomnia that are related to disturbances in the normal secretion of the
      hormone.

PMID- 9556099
TI  - Guidelines for prescribing melatonin.
AB  - Although compelling logic suggests that melatonin may be effective for a variety
      of disorders, there are few empirical clinical studies. The optimal dose of
      melatonin is not clear; most studies have used doses that produce
      supraphysiological blood levels. The timing of melatonin administration is
      important. Melatonin has few immediate side-effects except drowsiness, but the
      effects of chronic administration are unclear. Melatonin may be effective in
      reducing jet lag. In elderly patients with poor sleep and documented low
      melatonin production, melatonin may be helpful. In several studies, melatonin has
      been shown to shorten sleep latency. Further studies are needed to clarify the
      efficacy and safety of melatonin.

PMID- 9556098
TI  - Use of melatonin for sleep and circadian rhythm disorders.
AB  - Although not licensed as a drug, melatonin is widely sold as a nutritional
      supplement in the USA for its purported sleep-promoting and antiageing
      properties. In this article, we provide some guidelines for its use in sleep
      disorders medicine. In brief, melatonin appears to promote sleep by producing
      corrective circadian phase shifts, thereby improving the alignment of the
      endogenous sleep propensity rhythm with the desired sleep schedule. Melatonin may
      also have a direct soporific effect, especially when administered during the day.
      We suggest that the direct soporific action results from the release of
      accumulated sleep drive by melatonin's attenuation of the circadian alerting
      signal. Melatonin has not been proven safe by the usual clinical trial criteria,
      but to date no catastrophes have been related to its use. Also, there is little
      information about the safety and efficacy of chronic administration.

PMID- 9556100
TI  - Cutaneous findings related to cardiovascular disorders.

PMID- 9556101
TI  - Dermatologic aspects of antiphospholipid syndrome.

PMID- 9556103
TI  - Trichosporosis (white piedra) in Kuwait.

PMID- 9556102
TI  - Proliferations of the epidermoid cyst wall.

PMID- 9556104
TI  - Pathogenesis of Hashimoto's thyroiditis: apoptosis revisited.

PMID- 9556105
TI  - AA line.
AB  - BACKGROUND: The transverse skin line of the upper part of the forearm is a
      common, easily recognized condition; however, this line has not been defined
      clearly and does not correspond to other previously reported skin lines. Our
      purpose was to assess the nature and associated conditions of this skin line, and
      characterize the histopathologic features. METHODS: We examined 1343 healthy
      Korean people. The persons showing this skin line were evaluated by history and
      physical examination. Skin biopsy was performed on 10 persons showing this line:
      on one side at both the lesion and contralateral, non-lesion sites. RESULTS: A
      total of 480 persons (36.4%) showed this line. The incidence was significantly
      higher in the female group and in the group between 10 and 19 years of age.
      Histopathologic examination showed subtle edema, separation and fragmentation of
      collagen bundles, and vasodilation at the transverse skin line. CONCLUSIONS: We
      conclude that this skin line represents a newly defined skin line, and propose
      the term AA line.

PMID- 9556106
TI  - Histopathologic features of the spontaneous pustular lesions of Behcet's
      syndrome.
AB  - BACKGROUND: Papulopustular lesions are common in Behcet's syndrome (BS). A debate
      exists as to whether they are different from ordinary acne. This has important
      clinical and pathophysiologic implications. OBJECTIVE: The aim of this study was
      to evaluate the histopathologic features of papulopustular lesions seen both in
      BS and acne vulgaris (AV). METHODS: Representative samples were obtained from 17
      patients with BS and six patients with AV. The detailed histopathologic features
      were evaluated by a dermatopathologist blinded to the diagnoses. RESULTS:
      Considering the epidermis, follicle epithelium, and dermis separately, no
      differences could be found between the two groups. CONCLUSIONS: The
      papulopustular lesions seen in these two disorders cannot be distinguished on the
      basis of clinical and histopathologic findings.

PMID- 9556107
TI  - Epidemiologic analysis and clinical course of 84 consecutive cases of pemphigus
      in eastern Sicily.
AB  - BACKGROUND: The purpose of this study was to examine the clinical and
      epidemiologic features of pemphigus in eastern Sicily. METHODS: All new cases of
      pemphigus seen in the Dermatology Clinic at the University of Catania during the
      period January 1982 to June 1996 were studied retrospectively. RESULTS: Eighty
      four patients with pemphigus represented 1.3% of 6653 patients admitted to our
      clinic in a 13.5-year period, with an average annual incidence of six cases per
      year. The most common form of presentation was pemphigus vulgaris (PV) (75%),
      followed by pemphigus erythematosus (17%), pemphigus herpetiformis (6%), and
      pemphigus vegetans (2%). In 6% of PV patients, the oral lesions were not followed
      by skin involvement, and the lag time between the onset of illness and the final
      diagnosis in five PV cases was prolonged, ranging from 4 to 7 years, probably due
      to the mild clinical presentation of the disease. Two trauma-related PV cases
      were documented; in one case, the blisters were located in a surgical scar and in
      the other in a burn scar. CONCLUSIONS: Our findings showed that pemphigus has a
      relatively high prevalence in eastern Sicily compared with other Italian regions;
      PV is the most common variant, and may have a mild course not always requiring
      aggressive therapy.

PMID- 9556108
TI  - Diagnostic value of IgM deposition at the dermo-epidermal junction.
AB  - BACKGROUND: Granular immunoglobulin M (IgM) deposits at the dermo-epidermal
      junction (DEJ) are common in lupus erythematosus (LE); however, weak,
      interrupted, linear and granular patterns of IgM at the DEJ have been reported in
      sun-exposed skin in normal adults and in a heterogeneous group of diseases.
      MATERIALS AND METHODS: We analyzed 200 patients with positive IgM direct tissue
      immunofluorescence deposition at the DEJ, alone or in combination with other
      immunoreactants, in order to determine the diagnostic significant of IgM
      deposition at the DEJ. RESULTS: IgM deposition at the DEJ, commonly in
      combination with other immunoreactants, was associated with LE in 57.5% of
      patients. In cases with IgM deposition alone at the DEJ, only 12% had LE (strong
      intensities). IgM deposition at the DEJ was associated with other dermatoses in
      42.5% of patients. In non-lupus patients, IgM deposition was the sole finding in
      59% of cases, and was weaker and more focal than in LE patients. CONCLUSIONS: IgM
      deposition at the DEJ in patients with LE tends to exhibit a strong intensity and
      is commonly detected in combination with other immunoreactants. IgM deposition
      alone at the DEJ, especially of weak intensity or focal in pattern, is noted in
      non-lupus patients, and has less diagnostic significance.

PMID- 9556109
TI  - Trichloroacetic acid in dermatology of 1911.

PMID- 9556110
TI  - Value of routine diagnostic criteria of bullous pemphigoid.
AB  - BACKGROUND AND DESIGN: The clinical, histologic, and direct (DIF) and indirect
      (IIF) immunofluorescence findings are used in a critical, although arbitrary,
      manner in the routine diagnostic process of bullous pemphigoid (BP). Our purpose
      was to estimate their relative value. In the present retrospective study, a
      follow-up of at least 18 months was used as a prerequisite for the final
      diagnosis of BP (63 patients) and controls (n=159). RESULTS: The clinical,
      histologic, DIF, and IIF diagnostic criteria of BP were found to vary
      independently of each other. Positive DIF was the most sensitive (90.5%) typical
      for BP histology and positive IIF were the most specific (99%). Immunopathologic
      tests were the most valuable, especially in the atypical varieties of BP. Nearly
      25% of patients in this group would have been misdiagnosed if IF tests had not
      been performed. Atypical cases (40%) seemed to represent a clinical continuum
      over the whole spectrum of the disease. Patients with exclusively immunoglobulin
      G (IgG) and C3 basal membrane zone (BMZ) deposits were significantly more often
      seropositive than the rest of the DIF-positive cases; however, the class of BMZ
      immunoreactants varied according to the site of biopsy. C3 was almost invariably
      deposited at the BMZ of DIF-positive patients. When Igs were also present, they
      were only exceptionally (5% of cases) of greater fluorescence intensity than C3.
      CONCLUSIONS: The combination of clinical data plus one positive immunopathologic
      test provide the best combination of sensitivity and specificity (98%), and seem
      to be most appropriate in defining patient populations for study purposes. The
      relationship between the classes of immunoreactants should be better evaluated
      with reference to the site of skin biopsy. It may be suggested, however, that the
      likelihood of BP existence is very low when in vivo C3 is absent or of lower
      intensity of fluorescence than the concomitant Ig(s).

PMID- 9556112
TI  - Epidemiologic observations on the natural course of pemphigus vulgaris.
AB  - BACKGROUND: During the last 20 years, few prospective studies on the natural
      course of pemphigus vulgaris (PV) have been performed. METHODS: Various
      correlations of disease duration, clinical activity fluctuations, serology, and
      coexistence with other disease states were analyzed with regard to their impact
      upon the natural history of pemphigus. Thirty-seven consecutive PV patients were
      involved in this 1-year retrospective follow-up study. RESULTS: The disease
      activity decreases with time, but when exacerbated it is of unpredictable
      intensity; skin involvement is equally distributed between the sexes; relapses
      occur mostly during the first 2 years after disease onset, and can be marginally
      predicted by autoantibody titers. CONCLUSIONS: Notice should be taken of the
      relative frequencies of PV associated with neoplasia, ionizing radiation, and
      familial occurrence.

PMID- 9556111
TI  - Familial pemphigus vulgaris in mother and daughter.
AB  - BACKGROUND: Pemphigus vulgaris is an autoimmune disease in which genetics appears
      to be of basic importance. Although association with certain human leukocyte
      antigen (HLA) alleles has been found in some ethnic groups and individuals, no
      true disease susceptibility genes have been established, and familial cases are
      very unusual. METHODS: We report a Polish family with pemphigus vulgaris in the
      mother and daughter. The diagnosis was confirmed by cytologic, histologic, and
      immunofluorescence studies. RESULTS: The course was severe and the disease long
      lasting in the mother, probably due to treatment with small doses of
      corticosteroids without immunosuppressive drugs. In the daughter, treated with
      larger doses of corticosteroids and azathioprine, the lesions regressed within 4
      months, after which maintenance therapy was instituted with 10 mg of prednisone
      daily. The HLA studies performed in the daughter and her three children after the
      mother had died showed identical haplotypes in both the patient and the healthy
      children. The patient has given birth to a healthy child while still having a
      high titer of intercellular (IC) antibodies. CONCLUSIONS: The familial occurrence
      of pemphigus in first-degree relatives is suggestive of inherited susceptibility
      to the disease, transmitted as a dominant trait. The identical haplotypes in the
      healthy children of the patient favor the role of other, unknown factors required
      for the development of the disease in predisposed individuals.

PMID- 9556113
TI  - Cerebriform sebaceous nevus.
AB  - A 20-year-old man presented with a well-defined, soft to firm, freely mobile
      pinkish-yellow plaque of 9.5 cm over the right parieto-occipital region with a
      typical cerebriform appearance. In total, nine folds were present with short
      black terminal hair in the sulci area. There was no follicular plugging. Skeletal
      survey and neurologic and ophthalmologic assessments were normal. Skin biopsy was
      compatible with sebaceous nevus showing mature sebaceous glands in the upper
      dermis and mature apocrine glands in the lower dermis with malformed hair germ.

PMID- 9556114
TI  - Giant vascular eccrine spiradenoma.
AB  - A 60-year-old man suffering from cardiac insufficiency consulted the Dermatology
      Department, Inonu University Turgut Ozal Medical Center, because of a bleeding
      tumor on his right hypochondrium. The tumor had begun as a small nodule
      approximately 5 years before, and had grown slowly with time. A small,
      superficial ulcer had appeared on the lesion approximately 6 months previously,
      and slight bleeding had occasionally occurred. The patient had no pain and no
      other complaint except bleeding. Dermatologic examination revealed a violaceous,
      ulcerated, and bleeding tumoral lesion below the mid-portion of the right
      costochondral line. The tumor was a non-tender, hemispheric mass, approximately 3
      4 cm in size, adherent to the epidermis, but movable on the underlying tissue. An
      incisional biopsy was performed with diagnoses of dermatofibrosarcoma protuberans
      and desmoid tumor. Histopathologic examination revealed prominent blood-filled
      vascular spaces and clearly delimited cords, showing two types of cell. The
      vascular spaces contained a periodic acid-Schiff (PAS)-positive, granular,
      eosinophilic material. There was no malignant transformation. The lesion was
      totally excised and primarily sutured.

PMID- 9556115
TI  - Pseudo-Kaposi's sarcoma (Mali type).
AB  - A 75-year-old man presented with lesions on his right leg and on the dorsum of
      the penis, which had appeared 5 years ago following long distance travel. His
      right leg was swollen, and there was a dark-violet-colored, slightly elevated
      lesion extending to the thigh and penis. Histologic examination revealed
      thickening of the arteriolar walls and diffuse proliferation of the vascular
      structures surrounding the arterioles and dissecting the dermal collagen fibers.
      Immunohistochemical staining for Factor VIII R-A reacted positively with
      arteriolar endothelium, but was negative on thin-walled vascular spaces. Femoral
      angiography showed multiple fine arteriovenous (A-V) shunts especially at the one
      third distal lower region of the right leg.

PMID- 9556116
TI  - Malignant nodular hidradenoma.
AB  - A 54-year-old male farmer was seen in May 1990 with a violaceous, exulcerated
      tumor, 2x1.5 cm in diameter, localized to the sternal area of the chest. The
      tumor had been present for 30 years, showing slow progressive growth; it was
      excised, but recurred 2 years before our initial evaluation. The tumor was again
      excised with a wide free margin. The histopathologic study showed an ill-defined,
      epithelial neoformation, formed by lobules of clear polygonal cells at the deep
      dermis and subcutaneous tissue; there was a second group of smaller cells with a
      basaloid aspect, a few of them presenting slight atypia. The tumoral lobules were
      surrounded by a myxoid material with vascular proliferation. The epidermis was
      normal. The histopathologic report was of a malignant nodular hidradenoma. No
      evidence of lymph node or distant metastases was found. One year after the
      excision, the tumor recurred at the surgical site, and an axillary lymph node
      showed metastatic cells. The lesion was excised for a third time and the patient
      was lost to follow-up.

PMID- 9556117
TI  - Witchcraft's syndrome: Munchausen's syndrome by proxy.
AB  - A 28-year-old man presented to the Dermatology Outpatient Department with a
      complaint of a burning sensation and soreness over his left cheek and left ear of
      10 days duration. It had started suddenly one morning when he woke up from sleep.
      He noticed a large blister with intense redness over his left cheek, associated
      with a burning sensation. There was a history of similar episodes over the past
      year, and all were sudden in onset, involved the cheeks, and were noticed after
      waking up from sleep. The patient volunteered that the episodes were always
      associated with a drinking spree the previous night. The individual was a healthy
      man with a wife and two children. The patient had been dependent on alcohol for
      the past year, and had been consuming alcohol for many years. On examination,
      there was an eschar occupying almost the entire cheek, with a few scattered
      lesions over the left tragus and left external ear. Peripheral scarring was noted
      with hyperpigmentation. While the angle of the mouth was superficially involved
      on the left side, the oral mucosa was normal. The right cheek also showed a few
      areas of scarring with patches of alopecia. There were no similar lesions
      elsewhere on the body. The peculiar history and the morphology of the lesion,
      that defied any classical diagnosis description, prompted us to interrogate both
      the man and his wife with regard to any serious differences. After much
      persuasion and on assurance of secrecy, the wife admitted that her husband was an
      alcoholic and was neglecting his family. When her efforts to prevent his drinking
      failed, she resorted to this drastic measure. Each time he passed out after a
      drinking bout, she poured acid on his cheek, hoping that the sequelae would
      frighten him from drinking. The acid was readily available to her as she used it
      for domestic cleaning. The couple were sent for psychiatric evaluation as
      Munchausen's syndrome by proxy (MSBP) or witchcraft's syndrome (WS) was
      suspected. Detailed psychiatric evaluation, together with psychometric
      assessment, revealed that the patient had an alcohol dependence (Axis-I
      diagnosis) and had a cyclothymic personality. Severe marital discord due to
      alcohol dependence had been present for the past 2 years. Evaluation of the
      patient's wife revealed that she was under significant psychologic distress. She
      showed major depressive symptoms with a histrionic personality. She revealed that
      she had resorted to using the corrosive out of frustration and anger over the
      behavior of the patient while he was in an inebriated state. The couple are
      currently undergoing psychiatric treatment.

PMID- 9556118
TI  - Crusted scabies of the scalp in dermatomyositis patients: three cases treated
      with oral ivermectin.
AB  - BACKGROUND: Cutaneous features in the scalp area among adult patients are rarely
      considered as a manifestation of scabies. METHODS: Three patients with clinical
      and laboratory data of dermatomyositis with scalp involvement (fulfill three or
      four of Bohan and Peter's criteria), of 4 years, 8 months, and 3 years duration,
      were seen at our department between 1995 and 1996. For relapses of ordinary
      scabies, they were treated repeatedly with local scabicide with temporary effect.
      After a symptom-free period during the treatment of dermatomyositis with
      corticosteroids and azathioprine, they developed diffuse redness with scales and
      crusts on the scalp areas. Light microscopy examination of material taken from
      these crusts showed an abundance of live mites. RESULTS: All patients were
      successfully cured of scabies with a twice oral dose of 200 microg/kg ivermectin
      within 8 days. CONCLUSIONS: Our patients with crusted scabies of the scalp and
      dermatomyositis prompted us to change our standard diagnostic and therapeutic
      regimens. Fascinating features included mimicry of scabies in patients with
      dermatomyositis, location of parasites on the scalp, suppressed cell-mediated
      immunity and successful cure of mange by ivermectin.

PMID- 9556119
TI  - Carl Heitzmann (1836-1896): physician and illustrator.

PMID- 9556120
TI  - The use of neuromuscular blocking agents in the emergency department to
      facilitate tracheal intubation in the trauma patient: help or hindrance?
AB  - PURPOSE: The purpose of this study is to examine the relationship between the
      occurrence of a difficult intubation and (1) the use of neuromuscular blocking
      agents (NMB) and (2) the presence of airway injuries. It is a retrospective
      analysis of data from a trauma registry. MATERIALS AND METHODS: Registry records
      of patients (n = 160) who required emergent endotracheal intubation or
      establishment of a surgical airway over a 3.5-year period in the emergency
      department were reviewed. Risk factors for difficult intubations were identified
      and analyzed using multivariate logistic regression analysis. RESULTS: NMB were
      used in 75% of patients requiring intubation. Fifteen percent of the intubations
      were considered difficult. No association was found between the presence of
      airway injuries and difficult intubations; however, the use of succinylcholine
      was associated with a lower risk of difficult intubations compared with
      intubations where a nondepolarizing NMB was used. CONCLUSIONS: The use of
      succinylcholine may result in fewer difficult intubations in the trauma patient
      than when a nondepolarizing NMB is used. The presence of airway injuries did not
      appear to predispose to difficult intubations.

PMID- 9556121
TI  - Delivery of hyperbaric oxygen therapy to critically ill, mechanically ventilated
      children.
AB  - PURPOSE: The purpose of this article is (1) to describe our method of mechanical
      ventilation and monitoring of critically ill children during administration of
      hyperbaric oxygen therapy (HBO2) in a multiplace chamber; and (2) to review the
      complications they experienced during transport to the HBO2 chamber and HBO2
      treatment. MATERIALS AND METHODS: A case series from a university-affiliated
      children's hospital and regional hyperbaric medicine treatment facility. Patients
      studied included all children who required HBO2 therapy while mechanically
      ventilated at any time between April 1985 and June 1995. RESULTS: Thirty-two
      children were treated with HBO2 while mechanically ventilated. Ages ranged from 3
      days to 11.3 years (mean 4.8+/-3.5 years). There were 22 males. Twenty-one
      children had necrotizing infections, 9 had carbon monoxide (CO) poisoning, and 2
      had iatrogenic arterial air embolism. Complications or events occurring during
      HBO2 therapy included hypotension (63%), bronchospasm (34%), hemotympanum (13%),
      and progressive hypoxemia (6%). The only complication during transport was one
      accidental extubation (3%). CONCLUSION: Hyperbaric oxygen therapy can be
      administered safely to most critically ill children in a multiplace chamber if
      they are monitored closely. Although complications are not uncommon, most can be
      managed easily by a team skilled in treating ill children and knowledgeable of
      possible complications of HBO2 therapy.

PMID- 9556122
TI  - The use of phentolamine in the prevention of dopamine-induced tissue
      extravasation.
AB  - PURPOSE: The purpose of this study was to determine whether dopamine-induced
      tissue extravasation injury could be prevented with phentolamine. MATERIALS AND
      METHODS: This was a prospective, randomized, blinded, and controlled animal
      study. Forty rats were evaluated to document the effects of dopamine compared
      with normal saline on tissue integrity, whether any tissue damage was
      concentration or volume dependent, and to determine the minimum concentration of
      dopamine resulting in tissue injury. Dopamine concentrations of 0.8 mg/mL and 3.2
      mg/mL were tested. In a second part of this study, an additional 40 rats were
      evaluated to assess the efficacy of two different doses of phentolamine (0.5 mg
      and 1 mg) or normal saline, when injected within 10 minutes of dopamine
      administration to prevent or reverse tissue extravasation. Extravasation sites
      were evaluated clinically and histologically at 2, 4, 6, and 8 hours and were
      compared with a baseline sample. Outcome measures were as follows: (1) prebiopsy
      was ectodermal erythema, induration, and blanching; (2) postbiopsy was bubbling,
      darkening, pallor, and hematoma of the muscle fascia. Histology included
      neutrophil migration, mast cell degranulation, edema, and hemorrhage. Fisher's
      Exact Test with the Bonferroni method were used for statistical analysis.
      RESULTS: Dopamine-induced extravasation resulted in tissue injury characterized
      by blanching and hematoma. Damage did not appear to be volume dependent, but may
      be related to the duration of infiltration. Subcutaneous injection with either
      dose of phentolamine appeared to be clinically effective in preventing tissue
      injury. However, microscopic evaluation of tissue samples was inconclusive.
      CONCLUSION: This study clinically supported the use of phentolamine for the
      prevention of dopamine-induced extravasation injury.

PMID- 9556123
TI  - Decelerating flow ventilation effects in acute respiratory failure.
AB  - PURPOSE: The purpose of this article is to analyze the effect of a pressure
      regulated volume-controlled ventilation mode on lung mechanics and gas exchange
      in patients with acute respiratory failure. MATERIALS AND METHODS: We ventilated
      10 patients with two pressure-limited modes: pressure-controlled ventilation (PC)
      and pressure-regulated volume-controlled ventilation (PRVC) in random order, for
      1 hour each. Patients were stabilized on volume-controlled ventilation (VC) for
      30 minutes before, between, and at the end of PC and PRVC to reach baseline
      conditions. At the end of every VC period and at 30 and 60 minutes of PC and
      PRVC, respiratory mechanics, gasometrics, and hemodynamic parameters were
      collected. RESULTS: We found no significant differences between the three VC
      periods. Comparing VC with the two pressure-limited ventilation modes, peak
      pressure decreased from 29.4+/-9.1 cm H2O (VC) to 25.9+/-8.4 (PC 60 minutes) and
      26.1+/-8.2 (PRVC 60 minutes), and PaCO2 decreased significantly from 38.6+/-3.1
      mm Hg (VC) to 36.7+/-2.8 (PC 60 minutes) and 36.8+/-2.9 (PRVC 60 minutes).
      CONCLUSIONS: Pressure-limited ventilation allows mechanical ventilation for the
      same tidal volume as VC but results in a lower peak inspiratory pressure and a
      slightly lower PaCO2. The mechanism responsible for this gas exchange effect is
      unknown but is probably related to a better air distribution of the decelerated
      flow. The clinical relevance of this phenomenon remains to be established.

PMID- 9556124
TI  - An approach to the treatment of severe adult respiratory failure.
AB  - OBJECTIVES: The purpose of this article is to evaluate outcome in adult patients
      with severe respiratory failure managed with an approach using (1) limitation of
      end inspiratory pressure, (2) inverse ratio ventilation, (3) titration of PEEP by
      SvO2, (4) intermittent prone positioning, (5) limitation of FiO2, (6) diuresis,
      (7) transfusion, and (8) extracorporeal life support (ECLS) if patients failed to
      respond. PATIENTS AND METHODS: This study was designed as a retrospective review
      in the intensive care unit of a tertiary referral hospital. One-hundred forty-one
      consecutive patients with hypoxic (n = 135) or hypercarbic (n = 6) respiratory
      failure referred for consideration of ECLS between 1990 and 1996. Overall,
      initial PaO2/FiO2 (P/F) ratio was 75+/-5 (median = 66). RESULTS: Lung recovery
      occurred in 67% of patients and 62% survived. Forty-one patients improved without
      ECLS (83% survived); 100 did not and were supported with ECLS (54% survived).
      Survival was greater in patients cannulated within 12 hours of arrival (59%)
      compared with those cannulated after 12 hours (40%, P < .05). Multiple logistic
      regression identified age, duration of mechanical ventilation before transfer,
      four or more dysfunctional organs, and the requirement for ECLS as independent
      predictors of mortality. CONCLUSIONS: An approach that emphasizes lung protection
      and early implementation of extracorporeal life support is associated with high
      rates of survival in patients with severe respiratory failure.

PMID- 9556125
TI  - "An approach to the treatment of severe adult respiratory failure (by Rich et al,
      Journal of Critical Care 13:26-36, 1998)".

PMID- 9556126
TI  - Paracrine regulation of cardiac myocytes in normal and septic heart.
AB  - A paracrine pathway for the regulation of cardiac contractile function by
      nonmuscle cells is documented in the heart. Coronary and endocardial endothelium
      release several diffusible agents, such as prostaglandins, endothelin-1, and
      nitric oxide, with an action on cardiac myocyte function. Cardiac diseases
      involving an immune or inflammatory mechanism, such as endotoxic shock, are now
      seen as conditions in which cross-talk between different cell types in the heart
      is clearly implicated. The potential biological relevance of inducible nitric
      oxide synthase in the myocardium, and the subsequent production of nitric oxide
      has been proposed as a mechanism of the cardiac depression observed in septic
      shock. In addition to cardiac myocytes, activated microvascular endothelial cells
      and cardiac endothelial cells may contribute to nitric oxide generation and,
      ultimately, to the depression of myocardial contractile activity during sepsis.
      This article reviews the local intercellular communication between cardiac
      myocytes and endothelial cells in the normal heart and discusses some of the
      mechanisms potentially claimed to depress heart function in sepsis.

PMID- 9556127
TI  - Glutamate receptors are expressed by bone cells and are involved in bone
      resorption.
AB  - The excitatory amino acid glutamate (Glu) is a potent neurotransmitter in the
      central nervous system and exerts its action via a variety of glutamate receptors
      (GluRs). Because we had previously shown that a poly-glutamate (poly-Glu) peptide
      stimulates bone resorption in vitro, an effect specific to Glu (Raynal, C.,
      Delmas, P. D., and Chenu, C. Bone sialoprotein stimulates in vitro bone
      resorption. Endocrinology 137:2347-2354; 1996), we investigated the possibility
      that bone cells express GluRs, and whether they may be important for osteoclast
      activity. Using immunocytochemistry on rat bone sections, we have shown that all
      mature bone cells (osteoblasts and osteoclasts) express GluRs, and that the
      ionotropic N-methyl-D-aspartate (NMDA) receptor 1 subunit (NMDAR1) appears most
      highly expressed. Osteoclasts isolated from rabbit long bones also possessed
      NMDAR1 GluRs. Bone resorption in vitro by isolated osteoclasts was inhibited by a
      monoclonal antibody directed against NMDAR1, as well as by two pharmacological
      antagonists of this receptor (D-AP5 and MK 801), which also antagonized poly-Glu
      stimulated bone resorption. These results suggest a possible new mechanism for
      regulating osteoclast activity and indicate that excitatory amino acids such as
      glutamate may be important local regulators of bone cell functions.

PMID- 9556128
TI  - Regulation of tenascin-C expression in bone cells by transforming growth factor
      beta.
AB  - Transforming growth factor-beta (TGF-beta) stimulates new bone formation when
      administered locally in vivo. The extracellular matrix protein tenascin-C, which
      is secreted by osteoblasts but absent from mineralized bone matrix, supports
      differentiation of cultured osteoblast-like cells. The current study was
      undertaken to determine whether expression patterns of tenascin-C in TGF-beta
      treated bone cells are in agreement with a role for this protein as a mediator of
      TGF-beta-stimulated new bone formation. Expression of tenascin-C was investigated
      by immunohistochemistry in calvarial bones of mice to which TGF-beta had been
      locally administered. Three days after initiation of daily TGF-beta treatment,
      strong staining for tenascin-C was seen in regions where periosteal
      osteoprogenitor cells were undergoing proliferation in response to TGF-beta; by
      comparison, staining of periosteal surfaces of control bones was weak and
      discontinuous. Seven days after initiation of a course of five daily injections
      of TGF-beta, tenascin-C staining was still enhanced in treated bones. The ability
      of TGF-beta to regulate expression of tenascin-C in osteoblast-like cells in
      vitro was investigated using an osteosarcoma-derived cell line (ROS 17/2.8). TGF
      beta caused a small but significant increase in secretion of tenascin-C into the
      medium, as determined by a solid phase dot immunoassay quantitated by
      densitometry. Western and northern blot analysis indicated that TGF-beta did not
      influence the pattern of expression of tenascin-C splice variants. These results
      indicate that TGF-beta stimulates osteoblastic tenascin-C expression and suggest
      that tenascin-C may act as a mediator of TGF-beta-induced new bone formation.

PMID- 9556129
TI  - Basic fibroblast growth factor induces osteoclast formation in murine bone marrow
      cultures.
AB  - We determined the effect of basic fibroblast growth factor (bFGF) on osteoclast
      like cell (OCL) formation in bone marrow cultures using C57BL/6 mice. Cells were
      cultured for 7 days with or without bFGF at various concentrations or 10(-8)
      mol/L 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. bFGF dose-dependently increased OCL
      formation per well (10(-10) mol/ L = 40 +/- 2; 10(-9) mol/L = 146 +/- 13; 10(-8)
      mol/L = 156 +/- 12) compared with control (< 7 per well). The effects of bFGF at
      10(-9) and 10(-8) mol/L were similar to that of 10(-8) mol/L 1,25(OH)2D3 (154 +/-
      11 per well). OCLs formed by bFGF were multinuclear, tartrate-resistant acid
      phosphatase (TRAP)-positive, expressed calcitonin receptors, and formed
      characteristic resorption pits. We also determined whether bFGF enhanced OCL
      formation during the early proliferative or late differentiating phases of the
      cultures. When bFGF (10(-8) mol/L) was added only on days 1-2 or days 3-4 of 6
      day cultures, there was a significant increase in OCL formation. In contrast,
      when bFGF was added only on days 5-6 few OCLs formed. Addition of bFGF at days 1
      6 or days 1-2 and days 5-6 caused similar increases in OCL formation, which were
      greater than OCL formation induced by treatment for days 1-2 or days 1-4. We
      examined the production of prostaglandin E2 (PGE2) in the cultures because bFGF
      is a potent stimulator of PGE2 synthesis in bone, and PGE2 stimulates OCL
      formation. bFGF treatment significantly increased PGE2 levels in 7 day cultures
      (controls = 1.4 +/- 0.1 nmol/L, 10(-8) mol/L bFGF = 132.5 +/- 0.7 nmol/L). In
      addition, treatment of marrow cultures with the prostaglandin synthesis
      inhibitors, indomethacin or NS-398 (both at 10(-6) mol/L), completely blocked
      bFGF-induced OCL formation. We conclude that bFGF stimulates OCL formation in
      C57BL/6 bone marrow cultures by mechanisms that require prostaglandin synthesis.
      This pathway is likely to be one mechanism by which bFGF stimulates resorption.

PMID- 9556130
TI  - Parathyroid hormone regulates the expression of the nuclear mitotic apparatus
      protein in the osteoblast-like cells, ROS 17/2.8.
AB  - The parathyroid hormone (PTH) signaling pathways that effect changes in
      osteoblast gene expression also alter the organization of the cytoskeletal
      proteins. PTH regulates the expression of nucleoskeletal proteins, such as
      nuclear mitotic apparatus protein (NuMA) and topoisomerase II-alpha. NuMA is a
      structural component of the interphase nucleus and organizes the microtubules of
      the mitotic spindle during mitogenesis. We propose that PTH-induced alterations
      in osteoblast cytoarchitecture are accompanied by changes in osteoblast nuclear
      structure that contribute to changes in gene expression. We used
      immunofluorescence and confocal microscopy to determine the effect of PTH on the
      expression and nuclear distribution of NuMA in the rat osteosarcoma cell line,
      ROS 17/2.8. Cells were treated with PTH or vehicle, then fixed and stained with
      NuMA antibody. Optical sections of interphase naive cells revealed a diffuse
      distribution of NuMA, interspersed with speckles, in the central nuclear planes
      but not in nucleoli. During the metaphase and anaphase, NuMA localized at the
      mitotic spindle apparatus. The percentage of NuMA-immunopositive ROS 17/2.8 cells
      decreased with increasing confluence, but serum starvation did not attenuate NuMA
      expression. Cell density-dependent changes in cytoskeletal organization were
      observed in these cells. PTH treatment induced changes in cytoskeletal
      organization and increased the percentage of NuMA-immunopositive ROS 17/2.8
      cells. These data suggest that PTH effects changes in osteoblast nuclear
      architecture by regulating NuMA, and that these alterations may be coupled to
      cytoskeletal organization.

PMID- 9556131
TI  - Macrophage colony-stimulating factor increases bone resorption by osteoclasts
      disaggregated from human fetal long bones.
AB  - Macrophage colony-stimulating factor (M-CSF) is known to play an important role
      in human and murine osteoclast formation. Although M-CSF has been shown to
      inhibit isolated neonatal rat osteoclasts from resorbing bone, its action on the
      mature human osteoclast has not been described. We now report that M-CSF
      increases osteoclastic bone resorption in a dose-responsive manner. Bone
      resorption by mature human fetal osteoclasts, including pit area, depth, and
      volume, was increased in the presence of M-CSF compared with vehicle. The number
      of osteoclasts in the cultures was similar after 2 and 18 h in the presence of M
      CSF, whereas there was a significant reduction in osteoclast number, whether
      assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive or
      vitronectin receptor-positive cells after 18 h in M-CSF-free cultures. The number
      of nuclei per osteoclast after 2 or 18 h in M-CSF was also similar and there was
      no difference in the number of vitronectin receptor-positive mononucleate cells
      at 2 and 18 h. This suggests that the increased bone resorption is likely to be
      accounted for by enhanced osteoclast survival in M-CSF compared with controls
      rather than by formation of new osteoclasts.

PMID- 9556132
TI  - Kinetic studies on epiphyseal growth cartilage in the normal mouse.
AB  - The synthesis of DNA was studied in the proximal tibial growth plate of 25-day
      old healthy NMRI mice by using the thymidine analog bromodeoxyuridine (BrdUrd),
      which is incorporated into cells in the S-phase. Such cells were found only in
      the upper three fifths of the morphologically defined proliferating zone. This
      zone was therefore subdivided into a functional proliferating zone (the S-phase
      zone) where most, if not all, chondrocytes proliferate, and a remaining
      maturation zone. The BrdUrd containing immunoreactive cells could then be
      followed at different intervals and they were found at the chondro-osseous
      junction after only 36 h. By using double-labeling with BrdUrd and
      iododeoxyuridine (IdUrd) the duration of cell cycle components could be
      estimated; that is, the time for DNA synthesis (S-phase), second gap and mitosis
      (G2 + M-phase), and remaining first gap (G1). We determined an S-phase time of
      7.1 h and an average cell-cycle duration of 36 h. The G2 + M-phase was estimated
      as 3.5-4 h, leaving an average G1-phase time of 25 h, which probably varies
      considerably between chondrocytes. By combining these data with morphometrical
      data regarding distances between cells, we calculated a total growth rate of 9.0
      microm/h. Of this rate, 80% was entirely related to the process of hypertrophy-
      that is, longitudinal expansion without any corresponding increase in cell number
      -and 75 % was the result of processes outside the S-phase zone. Five percent of
      the growth was due to the expansion of cell distances within the S-phase zone. In
      this way longitudinal expansion can be studied at different levels in the growth
      plate and the data permit calculation of changes in volumes of the extracellular
      matrix. The largest increases in matrix volume occurred in the hypertrophic zone.
      These data may serve as a basis for further studies on matrix turnover in
      relation to growth.

PMID- 9556133
TI  - Interaction of triiodothyronine with 1alpha,25-dihydroxyvitamin D3 on interleukin
      6-dependent osteoclast-like cell formation in mouse bone marrow cell cultures.
AB  - In mouse bone marrow cultures, the formation of osteoclast-like, that is,
      tartrate-resistant acid phosphatase-positive (TRAP+) and calcitonin (CT) receptor
      positive multinucleated cells (MNCs), induced by 10(-10) to 10(-8) mol/L
      1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], could be augmented by
      triiodothyronine (T3), which alone had no effect on osteoclast-like cell
      formation. The permissive effect of T3 increased the response to 1alpha,25(OH)2D3
      by approximately one order of magnitude. Linear concentration dependence was
      observed between 10(-11) and 10(-8) mol/L T3. Importantly, inhibition of
      prostaglandin synthesis by indomethacin significantly impeded osteoclast-like
      cell formation by 1alpha,25(OH)2D3 and abrogated the effect of T3 thereon. Basal
      interleukin-6 (IL-6) production by cultured marrow cells was significantly
      stimulated by 1alpha,25(OH)2D3. However, even at an exceedingly high
      concentration of 20 ng/mL, IL-6 was ineffective in inducing osteoclast-like cell
      formation. Therefore, any hormonally induced rise in IL-6 release from bone
      marrow cells could not account for the observed changes in TRAP+ MNC numbers.
      Nevertheless, the stimulatory effect of 1alpha,25(OH)2D3 on osteoclastogenesis
      was partially dependent on IL-6 because it could be significantly blocked by a
      neutralizing monoclonal anti-IL-6 antibody, and to the same extent by a
      monoclonal anti-IL-6 receptor antibody. Unimpaired signaling through the IL-6/IL
      6R system is also a prerequisite for the auxiliary effect of T3 on induction of
      osteoclast-like cells by 1alpha,25(OH)2D3. Our data provide evidence that
      1alpha,25(OH)2D3 induces osteoclast-like cell formation, at least in part, in an
      IL-6-dependent mode of action, which is also subject to modulation by T3. The
      mechanism of interaction of the two hormones apparently involves joint
      stimulation of prostaglandin synthesis.

PMID- 9556134
TI  - Low-energy laser irradiation stimulates bone nodule formation at early stages of
      cell culture in rat calvarial cells.
AB  - Although the acceleration of bone regeneration by laser treatment has been
      reported, the mechanisms of action of laser on bone are unclear. To determine the
      target cells responsible for the action of laser irradiation and roles of
      irradiation on these cells during bone formation, we investigated the effects of
      low-energy laser irradiation at various cell culture stages on cellular
      proliferation, bone nodule formation, alkaline phosphatase activity, and
      osteocalcin gene expression, employing rat calvarial cells. Osteoblast-like cells
      isolated from fetal rat calvariae were irradiated once with a low-energy Ga-Al-As
      laser (830 nm, 500 mW) at various cell culture stages (days 1-16). Laser
      irradiation at early stages of culture significantly stimulated cellular
      proliferation, ALP activity, and osteocalcin gene expression thereafter.
      Furthermore, laser irradiation at earlier stages of culture significantly
      stimulated a greater number (1.7-fold) and larger area (3.4-fold) of bone nodules
      that had developed in the culture dish on day 21. However, these effects could
      not be found by irradiation at a later date. These results suggest that laser
      irradiation may play two principal roles in stimulating bone formation. One is
      stimulation of cellular proliferation, especially proliferation of nodule-forming
      cells of osteoblast lineage, and the other is stimulation of cellular
      differentiation, especially to committed precursors, resulting in an increase in
      the number of more differentiated osteoblastic cells and an increase in bone
      formation. Both bone-formation-stimulating roles may be exhibited by laser
      irradiation to immature cells only.

PMID- 9556135
TI  - Interleukin-6 synthesis induced by prostaglandin E2: cross-talk regulation by
      protein kinase C.
AB  - We previously showed that prostaglandin E2 (PGE2) stimulates multiple
      intracellular signaling pathways as follows: by activation of adenylate cyclase;
      phosphoinositide (PI)-hydrolyzing phospholipase C and phosphatidylcholine (PC)
      hydrolyzing phospholipase D; and by induction of Ca2+ influx in osteoblast-like
      MC3T3-E1 cells. In this study, we investigated the effect of PGE2 on the
      synthesis of interleukin-6 (IL-6) and its regulatory mechanism in MC3T3-E1 cells.
      PGE2 significantly stimulated IL-6 secretion in a dose-dependent manner in the
      range between 1 nmol/L and 10 micromol/L. A23187, a calcium ionophore, or
      dibutyryl-cAMP significantly induced IL-6 secretion. The effect of a combination
      of A23187 and dibutyryl-cAMP on IL-6 secretion was additive. The depletion of
      extracellular Ca2+ by EGTA reduced the PGE2-induced IL-6 secretion. EP1 receptor
      antagonist inhibited the PGE2-induced IL-6 secretion. H-89, an inhibitor of cAMP
      dependent protein kinase, decreased the PGE2-induced IL-6 secretion. EP2 receptor
      agonist alone stimulated IL-6 secretion. However, EP4 receptor antagonist had
      little effect on IL-6 secretion. Calphostin C, a specific inhibitor of protein
      kinase C (PKC), enhanced the secretion of IL-6 induced by PGE2. The stimulative
      effect of PGE2 on IL-6 secretion was significantly enhanced in PKC downregulated
      MC3T3-E1 cells. Pertussis toxin enhanced PGE2-induced IL-6 secretion. These
      results strongly suggest that PGE2 stimulates IL-6 synthesis through both Ca2+
      mobilization from extracellular space via EP1 receptor and cAMP production via
      EP2 receptor in osteoblast-like cells, and that the PKC activation by PGE2 itself
      regulates oversynthesis of IL-6.

PMID- 9556136
TI  - Short-term treatment of recombinant murine interleukin-4 rapidly inhibits bone
      formation in normal and ovariectomized mice.
AB  - Estrogen deficiency contributes to an increase in bone resorption and bone
      formation characterized by a high rate of bone turnover. Interleukin-4 (IL-4) is
      a rapid and potent inhibitor of bone resorption. We examined the short term in
      vivo effects of recombinant murine IL-4 (rmIL-4) on bone remodeling in normal and
      ovariectomized mice. Eight-week-old mice were randomized into the following five
      groups: (1) sham-operated mice (sham); (2) sham-operated mice infused with rmIL
      4; (3) ovariectomized mice (ovx); (4) ovx infused with rmIL-4; and (5) ovx
      replaced by 10 or 20 microg of 17beta-estradiol (E2) for 14 or 28 days after
      ovariectomy, respectively. rmIL-4 at a dose of 5 microg/day was infused into ovx
      and sham for 3 days prior to sacrifice. Analyses were performed 14 and 28 days
      after operation. An increase in serum alkaline phosphatase and urinary
      deoxypyridinoline levels induced by ovariectomy was inhibited by the 3-day
      infusion of rmIL-4. In ovx, serum and urinary IL-6 levels were also increased
      significantly 14 days after ovariectomy, which were restored by E2 but not by
      rmIL-4. Histomorphometrical analysis of trabecular bone revealed that the 3-day
      infusion of rmIL-4 inhibited the high rate of bone turnover induced by
      ovariectomy, such as an increase in the osteoclastic surface (Oc.S/BS), number of
      osteoclasts per mm bone surface (N.Oc/BS), mineralized surface per mm bone
      surface (MS/BS), and bone mineral apposition rate (MAR). A significant decrease
      in the bone volume (BV/TV) observed in ovx was not modulated by a 3-day infusion
      of rmIL-4 prior to sacrifice. In sham, rmIL-4 also caused a significant decrease
      in the Oc.S/BS, N.Oc/BS, MS/BS, and MAR, but the BV/TV was not modulated by rmIL
      4. We conclude that short term infusion of rmIL-4 in vivo rapidly inhibits not
      only bone resorption but also its formation in both sham-operated and
      ovariectomized growing mice, resulting in a low rate of bone turnover without
      modulating bone volume.

PMID- 9556137
TI  - Immunolocalization and quantification of noncollagenous bone matrix proteins in
      methylmethacrylate-embedded adult human bone in combination with
      histomorphometry.
AB  - The noncollagenous proteins (NCPs) in the bone matrix comprise growth factors
      with distinct cellular effects and a series of proteins with less clear
      biological actions. In order to understand the role of these proteins in bone
      metabolism and in bone diseases, it is crucial to determine their localization
      and quantity in normal and pathological bone. We have developed an
      immunohistochemical method to detect osteopontin, osteocalcin, bone sialoprotein,
      osteonectin, decorin, biglycan, and the growth factors transforming growth factor
      beta, insulin-like growth factor-I, and bone morphogenetic protein-2 both in bone
      matrix and in bone cells of adult human bone embedded in methylmethacrylate.
      Immunohistochemistry and standard bone histomorphometry in adjacent sections
      allows the localization of the proteins to metabolically active sites in bone.
      The protocol works with several fixatives and with bone specimens obtained and
      embedded to over 20 years ago. Most importantly, we developed a procedure to
      specifically stain the mineralized matrix green in combination with a red
      staining of the NCPs. Using digital image analysis it is possible to quantify the
      relative amounts of NCPs (microm2 NCP area/microm2 mineralized matrix area).
      Within one biopsy of normal bone cut at four different heights (at a distance of
      100 microm), two adjacent sections were stained either for osteopontin or
      osteonectin. Thirty trabecular and 20 cortical microscopic fields were measured,
      and the NCP:mineralized matrix ratio was calculated. Stepwise analysis of the
      standard error of the mean of the NCP:mineralized matrix ratios showed that
      measuring about 50 microscopic fields is sufficient to obtain representative data
      with a small confidence interval. In conclusion, the present procedure enables to
      quantify NCPs and to relate their presence to metabolically active sites in bone.
      The quantification provides the opportunity to monitor differences in
      distribution (e.g., cortical vs. trabecular) and differences between normal and
      pathological conditions and to assess changes in matrix composition during
      treatment. This can be done by reanalyzing bone biopsies obtained in the past,
      e.g., during clinical trials. Therefore, the present technique will be a valuable
      tool for the study of noncollagenous bone matrix proteins in human bone.

PMID- 9556138
TI  - Dynamic stochastic simulation of cancellous bone resorption.
AB  - A stochastic simulation of cancellous bone resorption was developed and applied
      to a simple two-dimensional lattice structure representing the vertebral body.
      The simulation is based upon the concept of a basic multicellular unit (BMU)
      where net resorption (-deltaB.BMU) is considered at bone/marrow surfaces. The
      cancellous bone structure is defined as a binary matrix with the size of the
      pixels corresponding to a square element of approximately 20 microm dimension.
      The simulation considers both the probability that any surface pixel will be
      activated into a BMU and, if activated, the length of the resorption cavity. The
      relationship between relative stiffness and density for the simulation was
      predicted by finite element analysis. The stochastic simulation was iterated
      eight times with the mechanical properties assessed after each stage. Perforation
      of a single trabeculae was first observed at step 2, the structure completely
      lacking connectivity and mechanical integrity by step 8. The slope of the
      stiffness-porosity graph was greater than unity for the first five steps, but
      thereafter approached zero because the structure had lost connectivity and
      effectively collapsed. The eight-step simulation was repeated five times and
      demonstrated that, although the stiffness/density relationships were similar at
      the extremes of density, the dependence of stiffness upon density varied. This
      clearly demonstrates the stochastic nature of the simulation upon cancellous bone
      structure, and is probably indicative of a significant dependence of mechanical
      integrity upon perforation effects.

PMID- 9556139
TI  - Assessment of cancellous bone quality in severe osteoarthrosis: bone mineral
      density, mechanics, and microdamage.
AB  - The role of bone microdamage (microscopic cracks or microcracks and
      ultrastructural collagen matrix and bone mineral damage) in diseases such as
      osteoarthrosis and osteoporosis is poorly understood. Microdamage accumulation in
      vivo is influenced by age and cyclic loading, therefore, it would be useful if
      the burden of microdamage in bone could be assessed by noninvasive measures such
      as the radiological measurement of bone mineral density (BMD). The aim of this
      study was to investigate the relationship between BMD, compressive strength and
      stiffness, and microdamage in the cancellous bone of the proximal femur in
      patients with severe osteoarthrosis. Trabecular bone core samples, from the
      intertrochanteric region of the femur, were obtained from 34 patients, with a
      mean age of 70.3 +/- 11.1 years, undergoing total hip arthroplasty for
      osteoarthrosis. Cores selected from contact X-ray images were used for BMD
      measurement, compressive mechanical testing or left untested (uncrushed), en bloc
      staining for microdamage, and bone histomorphometry. The study shows a strong
      dependence of both the elastic modulus and ultimate failure stress of the bone
      samples on BMD and a significant relationship between the elastic modulus and
      trabecular anisotropy (Tr. An). In multiple linear regression, BMD and Tr. An
      together account for about 70% of the variance in the elastic modulus. Then
      including microcrack crack density (Cr.Dn) and damage volume fraction (DxV/BV)
      variables, Tr. An alone accounts for a relatively small amount of the variation
      (8.5%) in ultimate failure stress and elastic modulus. The Cr.Dn accounts for
      more of the variation in the ultimate failure stress than in the elastic modulus
      (50% vs. 7%). In this experiment, data for Cr.Dn provide a measure of damage
      associated with the ultimate failure of cancellous bone. In specimens that were
      not mechanically tested, in vivo microcrack accumulation increases exponentially
      with age. In conclusion, data from this study suggest that BMD and Cr.Dn are the
      major determinants of cancellous bone strength, whereas BMD and Tr. An are major
      determinants of cancellous bone stiffness. In bone specimens subjected to
      compressive testing there was no relationship between microdamage and BMD,
      suggesting that BMD cannot be used to monitor changes in the mechanical
      properties of bone due to microdamage accumulation.

PMID- 9556140
TI  - Vitamin D receptor gene polymorphisms and peak bone mass in southern Chinese
      women.
AB  - Controversial results were reported on the association of vitamin D receptor
      (VDR) polymorphisms and bone mineral density (BMD). We studied allelic
      frequencies of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms
      (RFLPs) in 144 normal healthy southern Chinese premenopausal women aged between
      30 and 40 years, and correlated their peak bone mass with the VDR genotypes. In
      comparison to Western populations, the B allele of the BsmI site is only found in
      5% of the Chinese population. The BBAAtt genotype is virtually nonexistent in
      Chinese people. Except for the slightly higher BMD values at the midlateral L-3
      vertebra (13.8%, p = 0.045) and at the Ward's triangle (13.3%, p = 0.08) in the
      bb subjects, no difference could be detected at other sites between the Bb and bb
      subjects. The same findings were observed when comparing the Tt to tt subjects.
      Analysis of the VDR genotype revealed that subjects with BbAaTt and BbAATt
      haplotypes had the lowest peak bone mass. Their L2-4 lumbar spine, midlateral L-3
      vertebra, and Ward's triangle BMD was 1.04, 0.90, and 0.75 standard deviation
      (SD), respectively, lower than the bbAATT counterparts, but none of the
      comparisons were statistically significant. However, with the low frequency of
      the B allele, our study had limited power to detect a small difference in the BMD
      of the various genotypes. In conclusion, although VDR polymorphism is believed to
      affect calcium absorption, this study failed to confirm a strong relationship
      between the VDR genotype and peak bone mass in our population with low dietary
      calcium intake.

PMID- 9556141
TI  - Assessment of bone mineral at appendicular sites in females with fractures of the
      proximal femur.
AB  - The prediction of hip fractures by measurements at remote sites or the
      improvement of predictive power by measurements at multiple sites could
      potentially increase the success of osteoporosis screening programs. In a cross
      sectional study on 137 postmenopausal women, we tested the hypothesis that bone
      assessment at the hip, the forearm, and the tibia are independently associated
      with osteoporotic fractures of the hip. Bone mineral densities, geometric
      features, and ultrasound properties were determined with hip dual X-ray
      absorptiometry, forearm peripheral quantitative computed tomography (QCT), and
      tibia speed of sound measurement. While the odds ratios for fracture
      discrimination per standard deviation decrease ranged between 3 and 4 for
      measurements at the hip, they were only 1.8 at the forearm and 1.4 at the tibia.
      Measurements at the tibia or the forearm were neither independently associated
      with osteoporotic hip fractures (p > 0.05) nor could any combination of
      measurements significantly increase the power for the identification of fractures
      as measured with receiver operating curves. Women who sustained trochanteric
      fractures were characterized by a generalized loss of bone mineral. Cervical
      fractures were associated with a decrease of bone mineral density at the hip, but
      no significant alterations in bone mass or geometric properties were observed at
      the tibia or at the forearm. Fracture risk prediction at the hip is therefore
      preferably performed by measurements at the hip itself. Peripheral QCT at the
      distal radius and tibial ultrasound seem capable of depicting women with an
      increased risk for trochanteric but not for cervical fractures. The risk
      assessment appears not to be improved by including information of cortical or
      geometric properties of the forearm.

PMID- 9556142
TI  - Effects of the bisphosphonate olpadronate in patients with carcinoma of the
      prostate metastatic to the skeleton.
AB  - Prostate cancer is predominantly associated with osteoblastic bone metastases,
      but an increase in bone resorption has been demonstrated consistently, both
      histologically and biochemically. For this reason, bisphosphonates, which
      effectively suppress bone resorption, have been used in patients with prostate
      cancer metastatic to the skeleton. We studied clinical and biochemical responses
      5 days and 3 months after administration of the new, potent bisphosphonate,
      olpadronate, in 28 patients with prostate cancer and bone metastases. All
      patients received 4 mg of olpadronate intravenously daily for 5 days. No
      additional treatment was given to the first 12 patients, while treatment was
      continued with oral olpadronate 200 mg daily in the following 16 patients. Serum
      alkaline phosphatase (ALP) activity was elevated in 93% of the patients and was
      positively correlated to urinary hydroxyproline excretion (r = 0.81, p < 0.0001),
      suggesting a coupling between bone formation and resorption. A rapid and
      significant suppression of bone resorption was observed in all patients after
      intravenous treatment. This was sustained for 4-6 weeks in all patients, but
      reversed thereafter in patients not receiving oral maintenance therapy. No
      significant changes in serum ALP activity were observed in either group during
      the 3 months of follow-up. At the start of treatment all patients had severe bone
      pain and 82% and 36% were using NSAIDs and/or opiates, respectively. Although
      clinical response was not a primary objective of the study, we observed that
      intravenous therapy was associated with a decrease in bone pain in 76% of
      patients and a reduction in the use of analgesics. At 3 months this response was
      generally sustained only in those patients who were maintained on continuous oral
      therapy (p < 0.05 compared with the group treated with intravenous olpadronate
      only). The clinical response thus appeared to parallel the biochemical changes in
      bone resorption.

PMID- 9556143
TI  - Enzyme immunoassay for a characteristic protein in the animal crude drug
      lumbricus.
AB  - A new method was developed to measure the content of a Lumbricus component in a
      traditional Chinese medicine (TCM). An antiserum specific to Lumbricus was
      elicited in a rabbit following immunization with a suspension of Lumbricus
      fragments. A characteristic antigen protein, 70 kDa, was found in Lumbricus and
      was purified almost to singleness using a column chromatography series of gel
      filtration and DEAE-Sepharose. A selected antibody enzyme immunoassay (SAEIA) was
      developed using the antiserum and the purified 70 kDa protein as a solid-phase
      antigen. The SAEIA was specific to Lumbricus species, and showed no cross
      reaction with any crude drugs other than Lumbricus. This SAEIA detected 70 kDa
      protein in the amount of 10 ng/ml with excellent reproducibility (coefficient of
      variation=3.0%) and an EC50 of 0.24 microg/ml. Using this assay, Lumbricus levels
      were easily determined in a Lumbricus-based TCM Kazecoll, but not in the control
      Kazecoll (Kakkonto) prepared without Lumbricus. The SAEIA for 70 kDa protein was
      simple, accurate, reproducible and may provide a general analytical method for
      the quality control of Lumbricus-based TCMs.

PMID- 9556144
TI  - Isolation of an Escherichia coli mutant which permits the high-level expression
      of a streptomycin-resistance gene derived from Pseudomonas aeruginosa.
AB  - Pretreatment with streptomycin at a low concentration influenced the
      susceptibility to streptomycin of a strain of Escherichia coli carrying a
      streptomycin-resistance plasmid, pSA1700, derived from Pseudomonas aeruginosa.
      This phenomenon was due to a mutation that occurred at about 10(-8)-10(-10) of
      frequency in a regulatory gene involved in gene expression on the chromosome of
      E. coli. A product encoded by the regulatory gene on the chromosome of E. coli
      might normally repress gene expression by binding to part of the promoter region
      of the streptomycin-resistance gene derived from P. aeruginosa.

PMID- 9556145
TI  - A carbon-centered radical as a reaction species in the DNA strand-breakage by D
      glucosamine.
AB  - Electron spin resonance(ESR) studies using 5,5-dimethyl-1-pyrroline N-oxide
      (DMPO) and sodium 3,5-dibromo-4-nitrosobenzensulfonate (DBNBS) as a spin-trapping
      agent revealed the formation of both hydroxyl and carbon-centered radical-derived
      spin adducts in Cu2+-containing 50 mM Tris-HCl buffered solutions (pH 7.1) of D
      glucosamine, D-mannosamine, and D-galactosamine, which were previously shown to
      have the ability to break the single-strand of plasmid pBR322 DNA in a nucleotide
      sequence-specific manner. HCl-free D-glucosamine has higher DNA breaking
      activity, and this activity is promoted more by the presence of Cu2+ than the
      original D-glucosamine hydrochloride, exhibits stronger radical signals in the
      ESR spectrum. It is suggested that D-glucosamine is unstable around neutral pH,
      being converted into certain intermediate(s) such as a dihydropyrazine compound,
      which generate(s) carbon-centered radicals, and that, besides the hydroxyl
      radical, the intermediate(s) is/are responsible for DNA strand breakage.

PMID- 9556146
TI  - Generation of immortalized murine forebrain cell lines expressing an alpha
      isoform of Ca2+/calmodulin-dependent protein kinase II.
AB  - Immortalized hybrid cells were generated by the somatic fusion of the cells from
      the forebrain of embryonic mouse with N18TG2 neuroblastoma cells. Three
      monoclonal hybrid cell lines, designated NF26, NF81, and NF83 (neuroblastoma
      forebrain hybrid cells), expressing an alpha isoform of Ca2+/calmodulin-dependent
      protein kinase II (CaM kinase II) were isolated, and their expression was
      demonstrated by immunoblotting and immunocytochemistry using a monoclonal
      antibody specific to the a isoform of the enzyme. The kinase activity of the
      hybrid cells was 2- to 3-fold higher than that of the parent neuroblastoma line
      N18TG2 cells. The neuronal origin of these lines was shown by their
      immunoreactivity to neurofilament protein, a neuron specific marker. Lines NF26,
      NF81, and NF83 are the first cell lines to express the gene of the alpha isoform
      of CaM kinase II in the brain.

PMID- 9556147
TI  - Apoptotic cell death induced by physarumin (hemagglutinin from myxomycete,
      Physarum polycephalum).
AB  - Physarumin, a carbohydrate-binding protein (hemagglutinin or lectin), was
      isolated from the plasmodium of Physarum polycephalum. Physarumin agglutinated
      not only several species of erythrocytes but also tumor cells such as AH109A
      ascites hepatoma cells, sarcoma 180 ascites cells and mouse leukemia P388 cell
      lines. Physarumin had tumor cell growth-inhibitory activity, and induced the
      apoptosis of P388 cell lines. Physarumin-induced apoptosis required binding to a
      68 kDa counter-receptor on the P388 cell surface. Since the agglutinating and
      antiproliferative activities of physarumin were inhibited by asialofetuin and
      thyroglobulin, respectively, it is suggested that physarumin reacts with the
      galactose moiety of carbohydrate chains of physarumin receptor.

PMID- 9556148
TI  - Characterization of ASK mice, a strain highly sensitive to anaphylactic shock.
AB  - A mouse strain named ASK that was originally isolated from El (epilepsy) mice has
      been shown to be highly sensitive to anaphylactic shock. Here, we characterized
      the bases of the sensitivity of ASK mice in comparison with the parental strain,
      El. More than 90% of ASK mice, but not El mice that had been sensitized either
      actively or passively, died within 1 h following an antigen challenge. The
      anaphylactic death was effectively blocked by diphenhydramine. Plasma histamine
      levels increased by 30-50 fold in ASK after the antigen challenge, but only a 2-3
      fold increase was observed in El mice. All (El x ASK) F1 mice, either male or
      female, showed an ASK-like phenotype, suggesting that the impaired plasma
      histamine response in El mice is due to some recessive mutation(s). Consistent
      with the plasma histamine responses, cultured mast cells derived from El bone
      marrow showed impaired potency to degranulate in response to surface IgE
      engagement, in contrast to ASK mast cells which undergo normal degranulation.
      Another characteristic feature of ASK mice is their sensitivity to histamine,
      since 75% of the mice were killed by the subcutaneous administration of 100-200
      mg/kg histamine, while C3H and BALB/c mice were resistant to even 600 mg/kg
      histamine. Taken together, the major bases of the susceptibility to anaphylactic
      shock in ASK mice are thought to be the enhanced sensitivity to histamine and the
      recovered degranulation machinery in mast cells that is impaired in El mice.

PMID- 9556149
TI  - Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5
      hydroxytryptamine (5-HT) receptor.
AB  - Interactions of anandamide (N-arachidonylethanolamide), an endogenous compound
      for cannabinoid receptors, with the receptors for 5-hydroxytryptamine (5-HT),
      benzodiazepine, and gamma-aminobutyric acid(A) (GABA[A]) receptors in bovine
      synaptic membrane were examined. Anandamide decreased the 5-HT receptor bindings
      at concentrations of 1-100 microM, although it did not cause any change in
      benzodiazepine or GABA(A) receptor bindings. A high concentration of anandamide,
      100 microM, significantly decrease both [3H]5-HT and [3H]ketanserin bindings. The
      present study revealed that the pharmacological activity of anandamide might be
      partially mediated through the 5-HT receptor.

PMID- 9556151
TI  - Suppression of synaptogenesis by epileptiform discharges in hippocampal slice
      culture.
AB  - Using an organotypic slice culture of the hippocampus, the effects of epileptic
      activities on synapse reorganization following axotomy were investigated. The
      maximal amplitude of field excitatory postsynaptic potentials that reflected the
      number of functional synaptic contacts were recorded 7 d after the mossy fibers
      or Schaffer collaterals were transected at 8 d in vitro. Fifty microM picrotoxin
      elicited epileptiform bursts, whose severity in the CA1 region was lower than
      that in the CA3 region. Synapse reformation of the mossy fibers was significantly
      prevented by picrotoxin, and that of Schaffer collaterals also tended to be
      attenuated. Ten microM bicuculline, 1 mM pentylenetetrazol or 2 mM 4
      aminopyridine also induced epileptic activities in the CA3 region and
      significantly depressed synapse formation of the mossy fibers. Using cultures of
      dispersed neurons, we found that the prolonged depolarization of membrane
      potentials promoted neurite outgrowth. Taken together, we concluded that the
      preventing effects of epileptic activities on synapse reorganization following
      axotomy was due to the inhibition of the synaptogenesis process, not to a
      blockade of axon outgrowth.

PMID- 9556150
TI  - Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidino-benzoyloxy)phenyl] propionate
      methanesulfonate (TT-S24) on experimental pancreatitis in rats.
AB  - The effect of methylcarbonylmethyl 2(S)-14-(4-guanidino-benzoyloxy) phenyl]
      propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats was
      examined in comparison with that of camostat. TT-S24 showed a preventive effect
      on increases in plasma amylase activity and pancreatic weight induced by cerulein
      injection. TT-S24 also reduced an increase in plasma amylase activity induced by
      taurocholate. TT-S24 effectively prevented the mortality induced by an injection
      of a mixture of trypsin and taurocholate. TT-S24 showed no effect on an increase
      in amylase activity 6 h after duodenum ligation (closed duodenal loop
      pancreatitis), indicating that the drug had no effect on the initiation and
      propagation step of closed duodenal loop pancreatitis. On the other hand, TT-S24
      reduced an increase in amylase activity 6 h after release of the duodenum
      ligation. TT-S24 showed anti-trypsin, anti-kallikrein, anti-thrombin and anti
      plasmin activities. The effect of TT-S24 on some experimental pancreatitis models
      was nearly equal to or somewhat more potent in most instances to that of
      camostat. Therefore, TT-S24 should be useful in the clinical treatment of
      pancreatitis.

PMID- 9556152
TI  - Differential effects of cytotoxic drugs on mortal and immortalized B
      lymphoblastoid cell lines from normal and Werner's syndrome patients.
AB  - We studied the effects of nine cytotoxic drugs on three groups of B
      lymphoblastoid cell lines transformed by Epstein-Barr virus (EBV): group 1,
      mortal cell lines from normal individuals; group 2, immortalized cell lines from
      normal individuals with strong telomerase activity; group 3, mortal cell lines
      from Werner's syndrome (WS) patients. Aminoglycoside antibiotics and alkylating
      drugs showed significantly stronger cytotoxic effects on immortalized cell lines
      than on mortal cell lines or the cell lines before immortalization. In contrast,
      topoisomerase II inhibitors showed no difference or they tended to be less
      cytotoxic to immortalized cell lines. Mortal cell lines from normal individuals
      and WS patients showed no difference in sensitivity against all the drugs
      examined except for the topoisomerase I inhibitor, camptothecin, which had a
      stronger cytotoxic effect on WS cell lines than other cell lines. We discuss the
      mechanisms underlying these cytotoxic effects.

PMID- 9556153
TI  - Study of the pharmacological effect of the bile salt, sodium scymnol sulfate,
      from Rhizoprionodon acutus. II. Prophylactic effect of scymnol on lesion
      development in a rat peripheral arterial occlusion model.
AB  - The effect of scymnol on the development of lesions in a rat peripheral arterial
      occlusion model, involving injection of 5% lactic acid into the femoral artery,
      was investigated. In this model oral administration of scymnol significantly
      prevented edematous swelling and development of lower limb lesions, including
      gangrene, and also reduced changes in blood coagulation parameters, platelet
      aggregation and retention rate at a dose of 10 or 30 mg/kg. However, it had no
      effect on these clotting system functions in sham-operated rats at a dose of 10
      mg/kg. The effects of scymnol were also compared with those of ticlopidine and
      argatroban. The findings suggest that scymnol may be clinically useful for
      preventing thrombotic peripheral arterial occlusive disorders. Its prophylactic
      action appears to be mainly due to its potent ability to protect against
      endothelial cell damage due to lactic acidosis.

PMID- 9556154
TI  - Appearance of compound K, a major metabolite of ginsenoside Rb1 by intestinal
      bacteria, in rat plasma after oral administration--measurement of compound K by
      enzyme immunoassay.
AB  - Enzyme immunoassay (EIA) for the determination of compound K (C-K), a major
      metabolite of ginsenoside Rb1 (G-Rb1) from Panax ginseng root by intestinal
      bacterial flora, was explored. Bovine serum albumin (BSA) was coupled to the C-26
      position on the unsaturated side chain of C-K. Beta-D-galactosidase was
      introduced at the C-26 position of the saturated side chain. Antiserum, obtained
      by immunization of rabbits with C-K-BSA conjugate, possessed high affinity and
      specificity toward C-K. The EIA for C-K by the double antibody method was
      established in the range of 0.1--100 ng/tube. Plasma C-K after the oral
      administration of C-K and G-Rb1 to rats was determined by the established EIA. C
      K was rapidly absorbed from the gastrointestinal tract after the administration,
      then slowly decreased. On the other hand, C-K appeared late and was retained for
      a long period of time in the plasma after the administration of G-Rb1, which
      itself is hardly absorbed.

PMID- 9556155
TI  - Mechanism of free radical-induced hemolysis of human erythrocytes. II. Hemolysis
      by lipid-soluble radical initiator.
AB  - Hemolysis of human erythrocytes induced by free radicals initiated from lipid
      soluble 2,2'-azobis(2,4-dimethylvaleronitrile) (ADVN) was examined under various
      conditions. From the ESR spectra of the spin-labeled erythrocytes, it was found
      that the fluidity of the membrane did not change during the radical-induced
      hemolysis. The curves of the time courses of the extent of oxidation and the
      conformational change of band 3 proteins were hyperbolic, though the hemolysis
      curves were sigmoidal. In spite of the necessity of lipid peroxidation, the
      peroxidation did not seem to relate directly to the hemolysis. It was observed
      that the hemolytic holes were formed by a lateral clustering of band 3, an anion
      exchange protein in erythrocytes. The competitive reaction model between lipid
      peroxidation and the redistribution of oxidized band 3 proteins, which was
      previously presented for the hemolysis initiated from water-soluble, 2,2'
      azobis(amidinopropane)dihydrochloride (AAPH), could explain well the curves for
      the hemolysis by ADVN. Further, the rates of lipid peroxidation at various
      concentrations of ADVN and AAPH were calculated on the basis of the hemolysis
      curves, and they were compared with the experimental values estimated from the
      curves for the lipid peroxidation. The curves which showed a dependence of the
      calculated rate constant on the concentration of radical initiators were similar
      to those of the experimental values. These results indicate that the competitive
      reaction model is appropriately represents the hemolysis induced by free radicals
      which also originated from lipid-soluble initiators.

PMID- 9556156
TI  - Antiproliferative constituents in Umbelliferae plants II. Screening for
      polyacetylenes in some Umbelliferae plants, and isolation of panaxynol and
      falcarindiol from the root of Heracleum moellendorffii.
AB  - Methanol extracts of 36 samples of 21 Umbelliferae plants were screened for
      polyacetylenic compounds using the ELISA for panaxytriol, and their
      antiproliferative activity was checked by MTT assay using the tumor cell lines MK
      1, HeLa and B16F10. The presence of antiproliferative polyacetylenes was
      suggested in Angelica acutiloba (fruit), Anethum graveolens (root), Bupleurum
      rotundifolium (fruit), Carum carvi (fruit and root), Coriandrum sativum (fruit),
      Cryptotaenia japonica (leaf), Glehnia littoralis (fruit), Heracleum
      moellendorffii (root) and Torilis japonica (fruit). Panaxynol and falcarindiol
      were successfully isolated from the root of Heracleum moellendorffii as
      antiproliferative polyacetylenes.

PMID- 9556157
TI  - A new experimental device for the measurement of moisture emission and heat
      release from respiratory organs and body surface.
AB  - A new experimental device was developed to investigate respiratory diseases. The
      moisture and heat released from respiratory organs and the body surface of a rat
      were determined by means of this device as well as the rectal temperature. The
      high recovery of results was statistically confirmed, and the measured values at
      various environmental temperatures were significantly different from each other.
      Some standard drugs, such as ephedrine, aminophylline and chlorpromazine, were
      examined. Their stimulant or depressant actions were clearly observed. The
      results of some traditional medicines for the treatment of rhinitis and bronchial
      asthma from this measuring system were consistent with their clinical
      applications. These results suggest that this new experimental system is not only
      effective in the experimental understanding of cold-hot syndrome, but also
      contributes to the evaluation of the effects of traditional medicines.

PMID- 9556158
TI  - Safe and efficient transdermal delivery of desmopressin acetate by iontophoresis
      in rats.
AB  - Iontophoretic delivery of desmopressin acetate (DDAVP) was assessed for delivery
      efficiency and drug stability, both in vitro and in vivo. The effect of current
      intensity and duration of current application on the decomposition of DDAVP was
      investigated in vitro. It was shown that when a current of 0.1 mA was applied for
      5 min, the decomposition of DDAVP was negligible. In vivo experiments under the
      same conditions showed that the antidiuretic response to DDAVP persisted for
      about 6 h. Furthermore, when this iontophoresis was repeated 3 times at intervals
      of 4 h, the antidiuretic response persisted for about 11 h. These results suggest
      that repeated short-term iontophoresis is a safe and effective technique for
      transdermal delivery of DDAVP.

PMID- 9556159
TI  - Direct transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester
      derivatives to the cerebrospinal fluid via the nasal mucous membrane in rats.
AB  - We investigated the absorption and transport of 2',3'-didehydro-3'-deoxythymidine
      (D4T) and its ester prodrugs from the nasal cavity in rats. The absorption of D4T
      and its acetate (C2-D4T) was rapid and almost complete, although the hemi
      succinate (Suc-D4T) was absorbed rather slowly; the plasma concentrations of the
      prodrug, Suc-D4T, and regenerated D4T remained unchanged throughout the
      experimental period (180 min). Concentrations in the cerebrospinal fluid (CSF)
      following intravenous (i.v.) and intranasal (i.n.) administration were also
      measured. After i.n. administration, drug concentrations were higher in the
      fraction derived from the subarachnoid space located close to the nasal mucosa
      than those in the fractions located far from the nasal cavity. This difference
      was not found following the i.v. administration of the drugs. Following nasal
      administration, the intact Suc-D4T was found in the CSF at a concentration higher
      than that of D4T, although transport of the intact prodrug to the CSF was not
      observed following i.v. administration. These results suggest that direct
      transport of the drugs from the nasal cavity to the CSF significantly contributes
      to the higher concentrations in CSF of D4T and/or its ester prodrugs, and
      indicate the possible value of nasal administration for the treatment of patients
      with AIDS dementia.

PMID- 9556160
TI  - Activation of murine kupffer cells by administration with gel-forming (1-->3)
      beta-D-glucan from Grifola frondosa.
AB  - The effect of gel-forming (1-->3)-beta-D-glucan on the immunological activities
      of murine kupffer cells was examined. A branched type gel-forming (1-->3)-beta-D
      glucan, GRN, was administered intravenously to mice. GRN associating to kupffer
      cells was detected by an immunohistochemical technique using anti-GRN antibody. A
      kinetic study of the activation of kupffer cells revealed that GRN could induce
      the enhanced production of cytokines and nitric oxide on 4 to 7 d after the
      administration. The activities are further augmented by adding GRN in the
      culture. The cytostatic activity of kupffer cells against murine lymphoma, EL-4,
      was also augmented by a time course similar to nitric oxide production. The
      cytostatic activity was reduced by adding an inhibitor of nitric oxide synthase,
      implying that the cytostatic activity of kupffer cells to EL-4 was dependent on
      nitric oxide. The administration of GRN increased the expression of CD11b, known
      as a beta-glucan receptor, on kupffer cells at day 7. The above data suggest that
      GRN could activate murine kupffer cells to enhance the production of cytokines
      and nitric oxide, and that the activation required 4 or 7 d, at least, after the
      administration with GRN.

PMID- 9556161
TI  - Hepatoprotective effect of Fe-TPEN on carbon tetrachloride induced liver injury
      in rats.
AB  - Fe(II)-tetrakis-N,N,N',N'(2-pyridylmethyl) ethylenediamine (Fe-TPEN) catalyzes
      the dismutation of superoxide, and blocks the toxic effect of paraquat on
      Escherichia coli growth and survival. We examined antioxidative effects of Fe
      TPEN on lipid peroxidation and t-butyl hydroperoxide induced cell damage. Fe-TPEN
      inhibited the FeSO4/H2O2 induced lipid peroxidation in the rat liver homogenates
      with an IC50 value of 30.2 microM, and protected Ac2F cell damage by t-butyl
      hydroperoxide in a dose-dependent manner (EC50 value is 2.6 microM). Also,
      hepatoprotective effect of Fe-TPEN (5 mg/kg, i.p.) was investigated using CCl4
      induced liver injury in rats. This complex inhibited the elevation of serum
      alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels in
      CCl4 induced liver injuries, and improved submassive necrosis and fatty
      degeneration of the hepatocytes. Fe-TPEN also prevented the loss of total and
      nonprotein SH contents, glutathione peroxidase and glutathione-S-transferase
      activity in cytosol of rat liver. Although the exact mechanism of action is not
      clear, antioxidative properties as well as attenuation of hepatocellular defense
      systems by Fe-TPEN seem to be important on its potent hepatoprotective effect in
      CCl4-intoxicated rat.

PMID- 9556162
TI  - Aromatization of 19-oxygenated androst-4-ene-3,6,17-triones with human placental
      microsomes.
AB  - To gain insight into the aromatization sequence of androst-4-ene-3,6,17-trione
      (1), a suicide substrate of aromatase, the aromatization of its 19-hydroxy and 19
      oxo analogs 2 and 3 with human placental microsomes, was studied using GC-MS.
      Steroids 2 and 3 were separately incubated with the microsomes in the presence of
      NADPH in air. The GC-MS analysis of the trimethylsilyl derivative of the
      aromatization product indicated that both the 19-oxygenated steroids 2 and 3 were
      aromatized to yield 6-oxoestrogens, 6-oxoestrone (4) and 6-oxoestradiol (5), in
      each experiment. The aromatization rates of substrates 2 and 3 were 605+/-48 and
      1794+/-75 pmol/mg protein/10 min, respectively. These relatively higher rates,
      compared to that of the parent steroid 1 (73.2+/-6.6 pmol/mg protein/10 min),
      indicates that the suicide substrate 1 is aromatized through the 19-oxygenated
      intermediates 2 and 3.

PMID- 9556163
TI  - Effect of arylthiolated 2,3-dimethoxy-1,4-benzoquinones on respiratory activity
      and lipid peroxidation in bovine heart mitochondria.
AB  - A series of arylthiolated 2,3-dimethoxy-1,4-benzoquinones was synthesized and
      tested for the effect on the respiratory system and the lipid peroxidation in
      bovine heart mitochondria (BHM). These quinones showed intense inhibitory
      activities on the respiratory system in BHM. Their inhibitory activity in the
      succinate oxidase system was greater than that in the NADH oxidase system. No
      difference between the difference spectra, with and without these quinones, of
      the reduced minus oxidized forms of cytochromes (cyt.) suggested that these
      quinones inhibit at the site after cyt. a+a3 in the respiratory chain. Moreover,
      these quinones were as efficient as exogenous ubiquinone-10 (UQ-10) for the
      inhibition of lipid peroxidation. 5- And 5,6-di-arylthio groups on the quinone
      ring were found to be favorable for inhibition of the respiratory system and
      lipid peroxidation. Our results suggest that arylthiolated 2,3-dimethoxy-1,4
      benzoquinones act as antioxidants by increasing the amount of endogenous reduced
      UQ-10 in BHM.

PMID- 9556164
TI  - Pharmacokinetics of intra-arterially administered pirarubicin in plasma and
      cerebrospinal fluid of patients with glioma.
AB  - The present paper investigates the pharmacokinetics of pirarubicin (THP) in the
      plasma and cerebrospinal fluid (CSF) of two patients with glioma during
      hyperosmotic disruption of the blood-brain barrier (HODBBB) and intra-arterial
      combination chemotherapy. A 42-year-old Japanese man (patient A) with
      glioblastoma and a 21-year-old Japanese woman (patient B) with astrocytoma
      received a course of HODBBB and intra-arterial combination chemotherapy with THP,
      methotrexate, peplomycin, and vindesine. Patient A was initially administered
      mannitol, followed by the infusion of anticancer drugs into the right internal
      carotid artery. Patient B was initially administered mannitol, followed by the
      infusion of anticancer drugs into the right internal carotid artery and,
      immediately thereafter, into the right vertebral artery. Samples of blood and of
      CSF in the brain ventricle were obtained. THP concentration was measured by HPLC,
      and the pharmacokinetic parameters of this drug were estimated in plasma and CSF.
      In both patients, the plasma concentration of THP peaked at the end of infusion,
      then decreased in a bi-exponential decay pattern during the remainder of the
      treatment period. THP was detectable in CSF beginning 1.0 h after the initiation
      of infusion, then was slowly eliminated from the ventricle. The maximum CSF
      concentration of THP was 0.97% of plasma in patient A and 0.89% in patient B. The
      CSF AUC of THP was 28.4% of plasma in patient A and 13.1% in patient B.

PMID- 9556165
TI  - In vitro release of tranilast from oily gels and penetration of the drug into
      Yucatan micropig skin.
AB  - For the transdermal delivery of tranilast (TL), a drug used for the treatment of
      skin diseases such as keloids and hypertrophic scars, its oily gels were
      prepared; its in vitro release and penetration into Yucatan micropig skin were
      evaluated. In the gels that consisted of hydrogenated soybean phospholipids (HSL)
      and octyl isononanoate (IOIN), a fatty-acid ester, the release of TL from the
      gels was proportional to the drug content, and the extent of TL released up to 6
      h from them was approximately 70% of the amount of applied TL. On the other hand,
      with the gels consisting of HSL and isocetyl isostearate (ICIS), the release of
      TL from the gels was about half of that from IOIN gels, even at the same drug
      concentration. When oily gels were used, the TL skin concentration was rapidly
      increased compared with the level obtained with suspensions. With 0.1% IOIN gel,
      a high concentration of TL (ca. 160 microg/g) in the dermis was obtained and
      continued until at least 48 h. These results suggest that oily gels may be useful
      for the topical application of TL.

PMID- 9556166
TI  - Urinary metabolites of valproic acid in epileptic patients.
AB  - The urinary excretion of valproic acid (VPA) and its metabolites (3-keto VPA, 3
      OH VPA, and VPA-glucuronide) in 6 epileptic patients was studied using gas
      chromatography-mass spectrometry. The amount of VPA and 3-OH VPA excreted in the
      urine was low (0.1-0.5% of the dose of VPA and 0.6-1.5% of the dose of 3-OH
      administered). The amount of 3-keto VPA and glucuronide (VPA-Glu) excreted was
      marked (5.8-26.2% and 13.1-88.7% of the dose of VPA administered, respectively).
      The urinary excretion of VPA and its metabolites by patients who have taken a
      normal amount of a VPA preparation was almost the same as that of healthy
      volunteers. Two epileptic patients who took a large amount of the VPA preparation
      showed a high excretion of VPA-Glu without an increase in their plasma VPA-Glu.

PMID- 9556167
TI  - Retention mechanism of imidazoles in connective tissue. II. Activation of
      imidazoles in cupro-ascorbate system for irreversible binding formation with
      aortic tissue in vitro.
AB  - In order to obtain an insight into the retention mechanism of drugs with
      imidazole moiety in the connective tissue, the in vitro characteristics of the
      interaction between 14C-labeled imidazoles (imidazole and its 2-methyl
      derivative) and slices of dog aorta were studied. We found that cupro-ascorbate
      catalyzed oxidative reactions for the imidazoles led to their irreversible
      binding with connective tissue, and that, from a study using protein modifiers,
      the aldehydic function intrinsic to the tissue protein was involved in the
      binding formation. This characteristic in vitro was observed under physiological
      conditions, hence it can be extrapolated to the in vivo situation and could also
      give a clue to the nature of the retention of imidazole-containing drugs in
      connective tissue.

PMID- 9556168
TI  - Occupational risks of zoonotic infections in Dutch forestry workers and muskrat
      catchers.
AB  - Lyme borreliosis (LymeB), Hemorrhagic fever with renal syndrome (HemoFRS),
      Lymphocytic choriomeningitis (LymphoCM), Tick-borne encephalitis (TickBE), Q
      Fever (QFever), and Weil's leptospirosis (Lepto) are known to be occupational
      diseases for rural outdoor workers. We investigated the occupational infection
      risks for these diseases in greater detail. Antibodies to these agents were
      assessed in 312 forestry workers and muskrat catchers, and in 356 matched office
      workers. Three levels of occupational exposure were distinguished: high for
      active forestry workers, low for supervisory forestry staff and muskrat catchers
      and zero for office workers. At high exposure the prevalence odds ratios (with
      95% CI between brackets) were: LymeB 15 (5.5-42), HemoFRS 11 (1.3-501), LymphoCM
      5.4 (1.0-50), TickBE 1.0 (0.3-3.0), QFever 1.0 (0.4-2.1), and Lepto 0 (0.0-33).
      No significant risk of infection was found at low exposure. Part of the present
      group had also been studied in 1989 and 1990. Within this cohort the conversion
      rates to Borrelia burgdorferi have been estimated for the periods 1989-1990 and
      1990-1993 as 0.23 and 0.066 year(-1), respectively, and the reversion rate as
      0.44 year(-1). The corresponding values for HemoFRS were 0.031, 0.018 and 1.42
      year(-1). Active forestry workers in the Netherlands are at high risk of
      infection by LymeB, HemoFRS and LymphoCM. Prevalence of antibodies to LymeB and
      HemoFRS appeared to reflect the levels of these infection hazards in recent
      history.

PMID- 9556169
TI  - Longterm survey (7 years) in a population at risk for Lyme borreliosis: what
      happens to the seropositive individuals?
AB  - In 1986, a 26% seroprevalence of IgG- anti-Borrelia burgdorferi antibodies was
      observed among 950 orienteers and the incidence of new clinical infections was
      0.8%. In 1993, a total of 305 seropositive orienteers were reexamined. During
      that time, 15 cases (4.9%) of definite/probable Lyme disease occurred in this
      seropositive group (12 skin manifestations and 3 monoarticular joint
      manifestations). Among the 12 definite cases, 9 showed new clinical infections (7
      EM, 1 acrodermatitis chronica atrophicans, 1 arthritis), and 3 were recurrent (2
      EM, 1 arthritis). The annual incidence (0.8%) in this seropositive group was
      identical to the incidence observed among the whole population in 1986. The
      individual antibody titer decreased slightly but the seroreversion rate was low
      (7%). Serology was not very helpful in identifying clinical cases and evolutions,
      and it can be stated, that a positive serology is much more frequent in this risk
      group than clinical disease.

PMID- 9556170
TI  - Epidemiological aspects of tuberculosis in the Padua Health District 1985-1996.
AB  - The present study was carried out in order to monitor the epidemiology of
      Mycobacterium tuberculosis disease in the Padua Health District over the period
      1985-1996 with a view to the situation in some population subgroups. The average
      annual rate per 100,000 persons per year was 7.9 with a peak in 1994 (15.6 per
      100,000 persons). The most significant variations are not per annum but between
      the periods 1985-1990 and 1991-1996 (average rates per 100,000 persons: 4.8 and
      10.9, respectively). The trend shows an increasing frequency in all age groups
      and especially among the elderly. Immigration from endemic areas and human
      immunodeficiency virus (HIV) infection appear to contribute to the increase the
      number of notified cases among adults. In the last four years an increase of
      tuberculosis cases was also observed among subjects with professional exposure
      risk. Improvements of programs both at national and regional level are believed
      to be essential to the tuberculosis control.

PMID- 9556171
TI  - The effect of follow-up on limiting non-participation bias in genetic
      epidemiologic investigations.
AB  - The use of a comprehensive follow-up strategy to limit non-participation bias was
      evaluated in a population-based case-control study of orofacial clefts. Birth
      parents were requested to provide exposure data, and index children and parents
      were asked to provide blood specimens. Follow-up included telephone or postal
      reminders every two weeks for up to three months. Consent to participate was
      received from 281 (76.6%) case mothers and 246 (72.4%) case fathers. The
      corresponding totals for controls were 279 (54.7%) and 245 (49.8%). Evaluation of
      participation rates by intensity of follow-up showed that 23% of case and 18% of
      control families consented without reminders (first stage); 81% of cases and 83%
      of controls agreed following one or two reminders (second stage); and the
      remainder of participants consented following three or more reminders (final
      stage). Cumulative distributions of sociodemographic characteristics differed
      little between second and final stage participants. Odds ratios for maternal
      multivitamin use were similar between second and final stage participants,
      whereas those for maternal and paternal smoking tended to decline. Although
      follow-up measures were necessary to enroll most families, use of more than two
      reminders did not appear to increase the representativeness of the sample;
      however, termination of recruitment after only two reminders would have led to
      different conclusions. Future studies require data collection protocols that
      encourage participation from all population subgroups, and one alternative is
      presented.

PMID- 9556173
TI  - Cytomegalovirus seroprevalence in French pregnant women: parity and place of
      birth as major predictive factors.
AB  - In this study we present data on cytomegalovirus (CMV) seroprevalence in pregnant
      women in France. One thousand and eighteen women were enrolled in a prospective
      study carried out in Grenoble. The overall rate of seropositivity, using a
      specific IgG ELISA test, was 51.5 % (95 % CI: 48.5-54.5). Among a homogeneous
      population of 873 women born in France with high or middle socioeconomic status,
      CMV seropositivity increased with age and parity. The seroprevalence according to
      age was found to depend on parity. It increased with age in women with no
      children or with only one; it was higher but no more age-dependent in women with
      two children or more. In addition, CMV seroprevalence was significantly higher in
      women born in southern France (51.6%) than in those born in northern France
      (37.4%), these findings being consistent with the existence, within France, of a
      gradient in seroprevalence rate, increasing from the North to the South. A
      logistic regression analysis reveals the place of birth in France as a major
      predictive factor of CMV antibody status (OR: 3.5) followed by age (OR: 2) and
      parity (OR: 1.7). In this study, we show an independent effect of parity on CMV
      seroprevalence, arguing for the importance of child-to-mother transmission;
      nevertheless, the latitude of the place of birth, even within a size-limited
      country such as France, appears to be a major predictive factor of CMV
      seroprevalence.

PMID- 9556172
TI  - Validity and reliability in reporting sexual partners and condom use in a Swiss
      population survey.
AB  - OBJECTIVES: To examine the validity and reliability of indicators of sexual
      behaviour and condom use in annual telephone surveys (n=2800) of the general
      population aged 17 to 45 for the evaluation of AIDS prevention in Switzerland.
      METHODS: A test-retest study with additional focused interviews was conducted on
      a subsample (n=138) of the respondents aged 17 to 22 years. RESULTS: The
      subsample included more French speaking respondents (OR: 1.7, CI: 1.1-2.5) and
      more people in a stable relationship (OR: 2.2, CI: 1.5-3-3) than the initial
      sample but did not differ in any other way, although no data is available on
      their attitudes towards sex. The reliability of the indicators considered was
      high: number of lifetime, casual sex partners in the last 6 months and condom use
      with them, acquisition of a new steady partner during the year and condom use
      with this partner, condom use at last intercourse. However, the focused
      interviews raised questions about the validity of some of these indicators,
      presumably due to imprecise wording of the questionnaire items. Among sexually
      active respondents, 12.5% (95% CI: 4.7-25.5) of the men included non-penetrative
      sex in the definition of 'sexual intercourse', but only 1.9% (95% CI: 0.1-10.3)
      of the women. The propensity for men of counting acts or partners with whom no
      penetration had taken place in the total reported sex acts or partners was not
      significantly associated with any socio-demographic variables. In addition, among
      the 15 respondents who had reported consistent condom use with casual sex
      partners at interview, 40% (95% CI: 16.3-67.7) admitted at reinterview that
      sometimes they also had unprotected sex. CONCLUSIONS: The reliability of reports
      on sexual behaviour and condom use in this Swiss evaluation survey is good. The
      indicators derived from the annual surveys are robust measures and the monitoring
      of trends seems to be based on reliable measurement. However, more research is
      required on the validity of the data.

PMID- 9556174
TI  - Physical activity and bone mineral density in Italian middle-aged women.
AB  - Osteoporosis is a major health issue in post-menopausal women on account of the
      association between low bone mineral density and fractures. A role of physical
      activity in the prevention and treatment of low bone mineral density is possible
      but still unclear. The relationship between low spine bone mineral density
      measured by means of dual photon absorptiometry at lumbar spines, and levels of
      past and recent physical activity has been assessed by means of a population
      based screening study carried out on 1373 women (age 40-64 years) in the North
      East of Italy. Physical activity at work and in leisure time was investigated for
      three specific periods of life: at age 12, between 15 and 19 years (during bone
      formative years), and in the recent years prior to the interview (30-39 or 50-59
      years). Data were analysed comparing low versus high bone mineral density tertile
      (i.e., 458 and 461 women, respectively), after controlling for other known
      contributory factors in the development of osteoporosis. A positive association
      emerged with leisure time physical activity, with significant trends at age 15-19
      (odds ratio (OR) for low versus high tertile of leisure time activity: 1.4, 95%
      confidence interval (CI): 0.8-2.4) and at most recent age (OR: 1.7, 95% CI: 1.1
      2.6). Risk trends with occupational physical activity were less clear and non
      statistically significant. The present Southern European cross-sectional study
      lends further support to the possibility that past and recent physical activity
      helps increasing bone mineral density in middle-aged women. Although the most
      beneficial type and intensity level of exercise has yet to be determined, the
      present results provide further evidence that participation in even moderate
      exercise programs should be encouraged.

PMID- 9556175
TI  - Secular trends in the osteoporotic fractures of the distal humerus in elderly
      women.
AB  - Osteoporosis, with its sequelae of fracture, is a major, continuously increasing
      threat to the health of the elderly, and therefore reliable epidemiological
      information is needed for assessment of the fracture development in the future
      and for effective fracture prevention. However, very little population-based
      information is available concerning the nationwide numbers, incidences and
      especially secular trends of osteoporotic fractures other than those occurring at
      the hip. We determined the current trends in the number and incidence of
      osteoporotic fractures of the distal humerus in Finnish women in 1970-1995 by
      collecting from the National Hospital Discharge Register all female patients aged
      60 years or more who were admitted to our hospitals in 1970-1972, 1974-1975, 1978
      1980, 1983-1985 and 1988-1995 for primary treatment of first osteoporotic
      fracture of the distal humerus. The fracture was defined as osteoporotic if it
      occurred on individuals aged 60 years or more as a consequence of a moderate or
      minimal trauma only (a fall from standing height or less). We also predicted the
      fracture development till the year 2030 by a regression model, a model that took
      into account the predicted changes in the fracture incidences and population at
      risk. The number and incidence (per 100,000 women) of osteoporotic fractures of
      the distal humerus in Finnish women aged 60 years or more increased from 42
      (number) and 11 (incidence) in 1970 to 175 and 30 in 1995. The age-adjusted
      incidence of osteoporotic fractures of the distal humerus also increased, from
      12/100,000 women in 1970 to 28/100,000 women in 1995. If this trend continues,
      the number of these fractures in Finnish women will be almost three-fold in the
      year 2030 compared with that in 1995. We conclude that the number of osteoporotic
      fractures of the distal humerus in elderly Finnish women is increasing more
      rapidly than can be accounted for by the demographic changes alone and therefore
      effective preventive measures are imperative to keep this problem in control.

PMID- 9556176
TI  - Traumatic brain injury in children in Denmark: a national 15-year study.
AB  - Demographic trends are reported concerning three types of traumatic brain injury
      (concussions, cranial fractures, and intracranial contusions/haemorrhages) among
      children in Denmark of ages up to and including 14 years, for a fifteen year
      period from 1979 through 1993. The data were derived from a national computer
      based hospitalization register and include 49,594 children, of whom 60% were boys
      and 89% had suffered a concussion. Virtually all injuries were the result of
      accidents. A major finding was that there has been a general decline in the
      incidence of traumatic brain injuries, especially for boys from 5 to 14 years
      old, suggesting a degree of success in preventive measures, particularly
      regarding road safety. The incidence of fatal cases of intracranial
      contusions/haemorrhages approximately halved over the 15 year period. However, as
      a proportion of all diagnosed cases, mortality from intracranial
      contusions/haemorrhages remained fairly constant at about 22%, perhaps because
      there have been no markedly successful innovations in acute care. Among children
      surviving a intracranial contusions/haemorrhages, rather considerable numbers
      were found to have been awarded disability pension at ages under 30.

PMID- 9556177
TI  - Injury mortality and morbidity among children in the United Arab Emirates.
AB  - The objective of this study was to identify the major causes of accident
      mortality and morbidity among children (0-14 years) in Al-Ain, United Arab
      Emirates (UAE). A retrospective descriptive study was set in the Al-Ain Hospital
      and Preventive Medicine Department, Ministry of Health, Al-Ain. Subjects were all
      patients aged 0-14 years who were seen at Al-Ain Hospital for injury during the
      12-month period January to December 1995, and all recorded deaths aged 0-14 years
      in Preventive Medicine Department from 1980 to 1995. RESULTS: Mortality: 301
      children (69.4% males, 30.6% females) died after accidents from 1980 to 1995. UAE
      citizens and other Arabs represented the majority of deaths. Most mortality
      (28.6%) occurred in the 1-4 year age group. Head and neck injury was the major
      type of injury causing death (57.5%). The most common cause of accidental death
      was road traffic accidents (boys 67.1%, girls 60.4%), followed by drowning and
      burns (8%). Morbidity: Pediatric trauma cases seen during 1995 totaled 17,498,
      representing one third of all patients attending the Hospital Emergency Room.
      About 70% of encountered injuries occurred among boys; 44.6% of cases were UAE
      citizens. The most common trauma type was contusion (40.2% boys; 40.6% girls),
      the most common type of trauma in boys and girls (30.4% and 36%, respectively).
      In the age group <5 years, the most common causes of trauma were fall (41.1%),
      blunt trauma (38.7%) and burns or scalds (64%), while in 5-9 year olds, the most
      common cause was road traffic accidents (40%). Finally, in 10-14 year olds, the
      most frequent causes were traffic accidents (32.8%) sharp objects injuries
      (38.3%), and fights and sporting (28.9%). CONCLUSION: More boys than girls
      presented with injury and the majority were nationals. Road traffic accidents
      mainly occurred in children over 10 years.

PMID- 9556178
TI  - Hospitalizations for infectious diseases in Jewish and Bedouin children in
      southern Israel.
AB  - Two different population groups reside in the Negev region of southern Israel and
      have equal, and free from financial barrier, access to tertiary care at a single
      regional hospital. The Jewish population has a largely urban and industrialized
      lifestyle, while the Moslem Bedouins are in transition from their traditional
      nomadic life to settlement. To examine the differences in morbidity patterns
      reflected in hospitalizations, the computerized hospitalization records of
      children <15 years of age, for 1989-1991 were used (n=15,947). Rates of
      hospitalizations for infectious diseases were significantly higher for Bedouins
      in comparison to Jews (250 and 121/10,000 child years, respectively, odds ratio
      (OR): 2.1, 95% confidence interval (CI): 2.0-2.2, p < 0.001). Rates of
      hospitalization per 10,000 child years in Bedouins and Jews for diarrhea were 114
      and 32 (OR: 3.7, 95% CI: 3.3-4.0, p < 0.001), respectively, and for pneumonia 55
      and 19 (OR: 2.9, 95% CI: 2.6-3.3, p < 0.001), respectively. In infants the
      differences were even more pronounced, especially for diarrheal diseases. In
      Bedouin children infectious diseases were associated with longer hospital stay,
      more pediatric Intensive Care hospitalizations (OR: 2.7, 95% CI: 1.7-4.5,p <
      0.001), and higher in-hospital mortality (OR: 5.7, 95% CI: 2.8-12.2, p < 0.001).
      Thus, Bedouin children are at higher risks of hospitalizations for infectious
      diseases in early childhood, as compared to Jewish children. This may reflect the
      differences in lifestyle, environmental and social conditions of the two
      populations.

PMID- 9556179
TI  - An outbreak of intrafamiliar hepatitis A associated with clam consumption:
      epidemic transmission to a school community.
AB  - An outbreak of hepatitis A is described involving thirteen cases in a town in
      central-northern Italy. The consumption of infected clams, caught in a polluted
      coastal area of the Adriatic Sea, caused hepatitis A in all five members of a
      family consisting of mother, father and children, two of whom attended primary
      school. The epidemic subsequently spread to the primary school with a secondary
      attack rate of 7.9%, 0 for female pupils and 18.9% for males. The epidemiological
      and environmental investigations showed that the critical exposure took place in
      the boys' toilet in the primary school (OR: 32.79, 95% CI: 6.83-157.45). To
      prevent the spreading of contagion, extra disinfection was carried out in the
      whole school and health education campaigns were mounted. The good basic hygienic
      conditions of the homes, together with the cooperation of school staff in
      surveillance and providing information, allowed the epidemic to be controlled.

PMID- 9556180
TI  - An outbreak of sheep-associated Q fever in a rural community in Germany.
AB  - In spring 1996, an outbreak of Q fever occurred among residents of a rural town
      (population: 300) in Germany. A retrospective cohort study was conducted to
      ascertain the extent of the outbreak and to assess potential risk factors for
      illness. In July 1996, all residents > or =15 years received a self-administered
      questionnaire and were offered Coxiella burnetii antibody testing. Residents were
      considered to have probable Q fever if they had a positive result for IgM C.
      burnetii antibodies by ELISA or possible Q fever if they had fever > or =39
      degrees C lasting >2 days and > or =3 symptoms (chills, sweats, severe headache,
      cough, aching muscles/joints, back pain, fatigue, or feeling ill) after 1 January
      1996. Two hundred (84%) of the 239 residents aged > or =15 years either completed
      the questionnaire or submitted blood for antibody testing. Forty-five (23%) of
      these 200 met the probable or possible case definitions. Onsets of illness
      occurred in January-June 1996. Cases were geographically distributed throughout
      the town. Persons reporting contact with sheep (32% vs 18%, RR: 1.8, 95% CI: 1.1
      2.9) and walking near a large sheep farm located next the town (34% vs 8%, RR:
      4.5, 95% CI: 1.7-12.2) were more likely to have met the case definition than
      those without these exposures. Fifteen of 20 samples from the large sheep flock
      were positive for C. burnetii antibodies. The sheep had lambed outdoors in
      December 1995-January 1996 while the weather was extremely dry. The timing of the
      outbreak after lambing, the uniform distribution of cases throughout the town and
      the absence of risk factors among most case-persons suggest airborne transmission
      of C. burnetii from the large sheep farm.

PMID- 9556181
TI  - Skin diseases in immigrants seen as out-patients in the Institute of Dermatology
      of the University of Rome 'La Sapienza' from 1989 to 1994.
AB  - In the Institute of Dermatology of the University of Rome 'La Sapienza' (IDURLS)
      from 1989 to 1994, 2198 immigrants from countries outside the European Community
      were seen as out-patients. Their personal and pathological data were collected by
      a particular software 'Questio', set up together with colleagues of the
      Interdepartimental Center for Scientific Calculous (ICSC) of the University of
      Rome 'La Sapienza'. The number of patients has been increasing from 326 in 1989
      to 436 in 1994. Most of the people were coming from Africa, but from 1989 to 1994
      the number of patients from the regions of ex-Yugoslavia has been increasing.
      About one third of the immigrants were unemployed, whereas 40% of them had a job
      (worker or employee), and the remaining 20% was composed by students and
      housewives. Most immigrants (1474 patients) were 20-39-year-old. Their data were
      compared with those of a control group composed by 2100 Italian people of the
      same age and sex, seen as out-patients in IDURLS in the same period. The most
      frequent skin disorders observed in immigrants were skin infectious or parasitic
      diseases, above all scabies. Excluding people with scabies, both immigrants and
      Italian patients shared the same skin diseases typical of young adult people:
      many fungal infections, many contact dermatitis and very few skin malignant
      tumors.

PMID- 9556183
TI  - Autoimmunity and B-cell malignancies.
AB  - There is evidence indicating that autoreactive B cells constitute a substantial
      part of the B-cell repertoire. This autoreactive repertoire secrete the so called
      natural autoantibodies characterized by their broad reactivity mainly directed
      against very well conserved public epitopes. They fulfill the definition of an
      autoantibody since they are self-reactive, but they are not self-specific. As
      yet, NAA directed against determinants of polymorphism have not been reported.
      Their germinal origin is suggested by their early appearance during ontogeny,
      their expression of cross-reactive idiotopes and structural studies of their
      sequence. As for the physiological role of the repertoire, we can assume that it
      may play a major role as a first barrier of defense. It is presently unknown
      whether these polyreactive B cells could constitute a pre-immune template which
      through an antigen driven process may be involved in the production of immune
      high affinity antibodies. This autoreactive B cell repertoire frequently
      undergoes malignant transformation, although there is controversy concerning the
      reasons accounting for this. It has been postulated that the continuous challenge
      of this autoreactive repertoire by self-antigens could create propitious
      conditions for malignant transformation to occur. However, it can be
      alternatively postulated, that overexpression of certain genes reflect what
      happens during ontogeny, since V genes expression is a developmentally regulated
      phenomenon and not all V genes are expressed during fetal life. Some of the genes
      that are recurrently expressed by these malignancies are also over-expressed in
      fetal repertoires and even in the adult normal B cell repertoire. We do not know
      whether it is the challenge by self-antigens or whether alternatively this over
      expression simply reflects what happens with the fetal repertoire which could
      have selective advantages for malignization.

PMID- 9556182
TI  - Genetic typing of human and food isolates of Listeria monocytogenes from episodes
      of listeriosis.
AB  - Ten clinical and food Listeria monocytogenes strains isolated during the
      epidemiological investigations of episodes of listeriosis (one outbreak and two
      sporadic cases) that occurred in northern Italy during 1993-1995 have been
      examined by DNA macrorestriction pattern analysis obtained by PFGE and RAPD
      typing, in order to confirm the food vehicle of infections. The same DNA profiles
      within the isolates from the three episodes were obtained by both techniques. The
      Apal and Smal PFGE profiles and RAPD patterns with primer OPM-01 confirmed the
      close relationship between strains from two distinct episodes. However, RAPD
      analysis with primer UBC-127 distinguished between these L. monocytogenes
      isolates.

PMID- 9556184
TI  - B cell compartments in multiple myeloma: flow cytometric analysis of their
      labelling indices and Bcl-2 protein expression.
AB  - Because recent reports have suggested that non plasmacytic tumor B cells are very
      rare in Multiple Myeloma (MM), we tried to characterize the B lineage in this
      disease by comparing by flow cytometry in the PB and BM of MM patients and of
      controls the proliferative activity (BrdU incorporation) and the Bcl-2 expression
      of different B cell subsets defined by cytoplasmic light chain, CD19 or CD10
      antigen expression. The labelling indices (LI) of CD19+ and CD10+ BM cells in
      treated patients were higher than in controls and untreated patients. Plasma cell
      LI (PCLI) were close to previously published values of PCLI flow assays and did
      not correlate with the LI of BM B cells. Bcl-2 expression by BM CD19+ and CD10+
      cells in patients was inferior to controls. These results agree with previously
      published data about the likely polyclonal nature of most pre PC B cells in MM.

PMID- 9556185
TI  - Adherent-free generation of functional dendritic cells from purified blood
      monocytes in view of potential clinical use.
AB  - There is increasing interest in dendritic cells (DC) that are capable of
      initiating antitumor immune responses. An in vitro cell differentiation method
      has recently been developed that uses GM-CSF and IL-4 to generate human DC from
      adherent blood mononuclear cells cultured on tissue culture plastic. These cells
      are competent for antigen uptake but express relatively low levels of co
      stimulatory molecules and thus correspond to immature resident tissue DC. We have
      adapted this method to consider some variables that are pertinent to clinical
      use, including a large scale differentiation of functional DC in a culture system
      suitable for clinical use. We report here that sizable numbers of monocytes
      purified by elutriation from blood leukocytes and cultured in Teflon bags develop
      with high efficiency into typical DC, as defined by morphology and membrane
      phenotype. When compared with usual adherent DC, cells generated under our
      adherent-free conditions exhibited lower CD1a expression and antigen capture
      capacity, but maintained the ability to present soluble antigens to T cells. They
      neoexpressed a high level of the co-stimulator molecule B7-2 (CD86) and was
      potent accessory cells for T cell proliferation, but they lacked the CD83 marker
      of DC full maturation. This study may constitute a prerequisite step for clinical
      investigations in tumor immunotherapy.

PMID- 9556186
TI  - Automated measurement of erythrocyte sedimentation rate and its relation to red
      blood cell concentration and plasma proteins.
AB  - A new automated erythrocyte sedimentation rate (ESR) system, the SEDISYSTEM was
      evaluated for its stability and accuracy. It offers automated mixing of vacuum
      collected blood for 5 minutes (min) and reading of the ESR for 20 min to generate
      values comparable with those of the Westergren method at 1 hour (h) and 2 h. The
      benefits are (1) simplified procedure, (2) reduction of biohazard and, (3)
      shortening of examination time. To evaluate the basic performance of this system,
      the stability of ESR values was first evaluated by keeping samples at room
      temperature for up to 20 h, during which time no remarkable change was observed.
      Next, a comparison between this system and the standard method of Westergren was
      conducted and good agreement was obtained. To determine the factors affecting ESR
      values, correlations were analyzed between the ESR obtained by SEDISYSTEM and the
      standard Westergren method for red blood cell concentration, hematocrit, and
      plasma proteins including fibrinogen, albumin and globulins (alpha1, alpha2, beta
      and gamma). Multiple regression analysis showed significant correlation with RBC,
      fibrinogen and gamma globulin. It is concluded from these results that SEDISYSTEM
      is a useful new tool for the measurement of ESR.

PMID- 9556187
TI  - Phorbol esters: useful tools to study megakaryocyte differentiation.
AB  - This review attempts 1) to enonciate recent observations made on the effects of
      phorbol esters on megakaryocyte cell lines, 2) to examine these effects taking
      into account megakaryocytopoiesis in vivo and 3) to demonstrate that phorbol
      esters stimulated megakaryocyte cell lines provide a good model to study the
      mechanisms governing megakaryocyte maturation.

PMID- 9556188
TI  - Fulminant hepatitis due to herpes simplex virus-type 2 in early phase of bone
      marrow transplantation.
AB  - Hepatitis due to Herpes Simplex Virus (HSV) is a rare and severe infection in
      patients with impaired immunity, as bone marrow transplanted. The antemortem
      diagnosis is often difficult to establish because the clinical features are
      nonspecific. We report an uncommon cause of fulminant hepatic failure in a
      neutropenic patient, 14 days after bone marrow transplantation. HSV-2 fulminant
      hepatitis occurred during acyclovir prophylactic treatment. No observation of HSV
      hepatitis in this context has been reported since prophylaxis is used. Because of
      the extremely high apparent mortality associated with HSV hepatitis, and the
      improved survival noted among the non-marrow-transplant recipients and prolonged
      survival seen in one marrow transplant recipient, it seems reasonable to urge
      early and aggressively acyclovir therapy. A liver biopsy seems to be
      indispensable in the case of hepatic failure in post-marrow-transplantation in
      order to make rapidly a diagnosis.

PMID- 9556189
TI  - Nomenclature and state of the art on alpha1-adrenoceptors.
AB  - The concept of alpha1-adrenoceptor subtypes was first suggested in the mid 1980s
      on the basis of the different affinities of certain alpha1-adrenoceptor
      preparations for the alpha-adrenoceptor agonist, oxymetazoline, and the
      antagonists, WB4101 and phentolamine. Subsequent characterization of alpha1
      adrenoceptors using radioligand binding and functional studies has led to the
      identification of three native prazosin high-affinity alpha1-adrenoceptor
      subtypes designated alpha1A, alpha1B and alpha1D, corresponding to the three
      alpha1-adrenoceptor subtypes (alpha1a, alpha1b and alpha1d) isolated by molecular
      cloning techniques. Since each of these three subtypes exhibits similar affinity
      for the selective alpha1-adrenoceptor antagonist, prazosin, [3H]prazosin can be
      used as a convenient probe to evaluate the interaction of compounds with these
      adrenoceptor subtypes. Considerable clinical experience over the last few years
      has provided convincing evidence to support the effectiveness of alpha1
      adrenoceptor blockade in the treatment of bladder obstruction due to benign
      prostatic hyperplasia (BPH). The distribution of alpha1-adrenoceptors in the
      human prostate tissue has shown that the predominant cloned alpha1-adrenoceptor
      subtype characterized by RNAase protection assays corresponds to the alpha1a
      subtype, formerly classified as alpha1c. Many of the alpha1-antagonists currently
      prescribed in the treatment of BPH do not exhibit in vitro selectivity between
      alpha1a-, alpha1b- and alpha1d-subtypes and yet they have good clinical tolerance
      in terms of low incidence of cardiovascular effects. One possibility to account
      for these findings is that another alpha1-adrenoceptor subtype could be
      implicated in human prostatic smooth muscle contraction. A recent report,
      although confirming the presence of an alpha1a-subtype in human prostate,
      suggested that an alpha1-adrenoceptor subtype with lower affinity for prazosin,
      designated alpha1L, which has not been cloned yet, is in fact the predominant
      alpha1-subtype involved in the contractile response of human prostatic smooth
      muscle to noradrenaline.

PMID- 9556190
TI  - The concept of uroselectivity.
AB  - Alpha1-adrenoceptor antagonists have been shown to decrease both the voiding and
      storage symptoms of benign prostatic hyperplasia (BPH). Based on the assumption
      that these symptoms can be attributed to the consequences of the increase in
      outflow resistance caused by noradrenaline stimulation of stromal alpha1
      adrenoceptors in the enlarged prostate, prostatic alpha1-adrenoceptors have
      become a target for therapeutic interventions. In some patients, alpha1
      adrenoceptor antagonists in common clinical use produce intolerable side effects
      which may be attributed to action on non-prostatic alpha1-adrenoceptors.
      Therefore, attempts have been made to find alpha1-adrenoceptor antagonists that
      have selective effects on the prostate ('uroselective' agents), to maintain
      efficacy in uroflow and eliminate adverse effects. The term uroselectivity has
      been used in various contexts, but drugs may be discussed as uroselective from a
      receptor pharmacological, physiological, or clinical perspective. Provided that
      the alpha1-adrenoceptor subtype in the prostate, bladder neck and urethra is
      uniform, unique, and cannot be found in other parts of the body, drugs with
      selectivity for this receptor could be called uroselective. However, available
      evidence suggests that (1) more than one alpha1-adrenoceptor subtype can be found
      in the lower urinary tract, and that the main alpha1-adrenoceptor mediating
      contraction still remains to be definitely defined; (2) the receptor(s) is (are)
      most probably not unique to the lower urinary tract, and (3) alpha1-adrenoceptor
      sites outside the prostate (with still undefined subtypes) may contribute to the
      lower urinary tract symptoms of BPH. Therefore, it does not seem possible to
      define uroselectivity in terms of selectivity for the alpha1-adrenoceptor(s)
      occurring in the prostate. Several animal models have been developed where the
      potency order of effects of various alpha1-adrenoceptor antagonists on blood
      pressure and urethral pressure have been measured simultaneously. Such models can
      be useful when screening drugs that may be developed for therapeutic use, but
      they also have limitations, since side effects that may be dose limiting
      clinically are not always related to a decrease in blood pressure. Certainly, a
      drug may be said to have physiological or functional uroselectivity if it lowers
      outflow resistance more effectively than it affects other defined physiological
      functions. A clinically meaningful definition of uroselectivity can only be made
      in man and considers desired effects on obstruction and lower urinary tract
      symptoms relative to adverse effects.

PMID- 9556191
TI  - Functional uroselectivity.
AB  - Alpha1-adrenoceptors mediating sympathetic tone to smooth muscle cells are
      located within the prostatic tissue, bladder base and in the proximal urethra,
      but are also widely distributed within a large number of tissues, especially the
      vascular beds and the central nervous system. Compounds clinically used in the
      symptomatic treatment of benign prostatic hyperplasia must therefore exhibit
      functional uroselectivity. This means that they should preferentially act on the
      lower urinary tract rather than the vasculature or central nervous system. Few
      clinically used alpha1-adrenoceptor antagonists show selectivity for the
      alpha1a/A-adrenoceptor subtype, whereas most of them have similar affinities for
      the three cloned subtypes (alpha1a-, alpha1b- and alpha1d-adrenoceptors). Recent
      data from in vitro studies assessing pharmacological uroselectivity and from in
      vivo models evaluating functional uroselectivity challenged the relevance of the
      affinity or the selectivity for a known alpha1-adrenoceptor subtype in predicting
      functional uroselectivity. They suggest instead that another subtype, like the
      alpha1L-adrenoceptor, might be functionally involved. In conclusion, the actual
      state of knowledge on alpha1-adrenoceptor subtype distribution and function, does
      not support a role of pharmacological uroselectivity in predicting functional
      uroselectivity. Furthermore, functional uroselectivity can be achieved in the
      absence of selectivity for the alpha1-adrenoceptor subtypes described so far.

PMID- 9556192
TI  - Clinical uroselectivity of alfuzosin in the treatment of benign prostatic
      hyperplasia.
AB  - The efficacy of alfuzosin in improving lower urinary tract symptoms and relieving
      bladder outlet obstruction has been demonstrated in numerous short- and long-term
      placebo-controlled studies and large-scale open studies, involving over 16,000
      patients with symptomatic benign prostatic hyperplasia (BPH). Treatment with
      sustained release alfuzosin (5 mg twice daily) for 3 months resulted in a 5-point
      reduction in the International Prostate Symptom Score and a 29% increase in
      urinary flow rate. The benefits of alfuzosin have been confirmed in general
      practice. A 1-year prospective study of 5,849 men with clinical BPH treated with
      alfuzosin showed a 51% reduction in mean total symptom score, with a 56% decrease
      in mean irritative symptoms. Improvement in health-related quality of life of 3
      years' duration have been recorded, including a reduction in the frequency of
      both diurnal and nocturnal micturition. Alfuzosin has a good safety profile.
      Unlike most other alpha1-blockers, a low risk of first-dose effect is seen,
      conveniently eliminating the necessity of dose titration at initiation of
      therapy. Postural symptoms related to orthostatic hypotension (a common side
      effect of alpha1-blockers) are infrequent, including in the elderly and
      hypertensives. Central nervous system effects are also limited due to poor
      penetration of the blood-brain barrier. In conclusion, the positive benefits/risk
      ratio of alfuzosin allows it to be classified as a uroselective alpha1-blocker,
      which provides a beneficial contribution to the management of symptomatic BPH.

PMID- 9556193
TI  - Clinical uroselectivity: a 3-year follow-up in general practice. BPH Group in
      General Practice.
AB  - The objectives of this open-labeled study were to assess the clinical
      uroselectivity of alfuzosin in a long-term follow-up study in general practice. A
      total of 3,228 patients with clinical benign prostatic hyperplasia (BPH) from 812
      centers were included in a prospective 3-year open-labeled study and treated with
      alfuzosin (immediate-release formulation) at the recommended dosage. Symptom
      score (Boyarsky, modified) and a 20-item BPH-specific health related quality of
      life (HRQL) score (Urolife BPH QoL 20), which included three questions on
      sexuality, were self-administered at baseline, 3, 6, 12, 18, 24, 30 and 36
      months. Symptom score was significantly reduced by 54% at 3 months and this
      reduction was maintained up to 36 months; the HRQL score was significantly
      improved by 45.4% at 12 months and this improvement was also maintained up to 36
      months. Alfuzosin was well tolerated: the quantitative and qualitative
      distribution of adverse events (AEs) was similar to that previously observed in
      placebo-controlled studies. 4.2% of the patients dropped out due to AEs. This
      study confirms the long-term safety profile of alfuzosin in general practice and
      highlights the need to measure HRQL in the context of clinical uroselectivity.

PMID- 9556194
TI  - Uroselectivity: myth or reality? Concluding remarks.

PMID- 9556195
TI  - Premenstrual syndrome and anxiety disorders: a psychobiological link.

PMID- 9556196
TI  - Treatment-resistant depression.
AB  - Our ability to treat depression has improved with the availability of receptor
      specific and chemically diverse groups of antidepressants. Even now, most of the
      short-term studies indicate that about 20% of depressed patients remain resistant
      to treatment. Therefore, it is important to properly assess the treatment
      resistant depressed (TRD) patients and to separate the truly refractory patients
      from those inadequately treated. Undiagnosed medical conditions should be
      eliminated. TRD is neither a clinically nor a biologically identifiable entity.
      As there are no established methods for the treatment of TRD, all options should
      be considered. The clinician can be enriched by the knowledge of the treatment
      modalities available, and yet, in treating an individual patient, clinical
      skills, intuitive judgment, family history of response to drugs and side effects,
      all play a vital role. Several of the approaches described in the paper indicate
      available methods and their merits in general but there is no way of ascertaining
      by which particular method a patient should be treated. The three common methods
      of treatment are substitution of one antidepressant drug for another, combination
      therapies and augmentation techniques. These are based on clinical experiences
      and not research findings. Therefore the treatment of TRD patients is more an art
      than a science. The physician should assess all the psychopathological,
      phenomenological and psychosocial variables to appropriately treat an individual
      patient.

PMID- 9556197
TI  - Do patients with panic disorder show a memory bias?
AB  - BACKGROUND: Cognitive models of panic disorder are becoming more and more
      influential. Therefore, research specifying cognitive processes related to panic
      disorder is needed. The present study investigated memory bias for panic-related
      material in patients with panic disorder. METHODS: Memory bias for panic-related
      material was investigated experimentally by a memory task requiring
      classification of panic-related and non-panic-related words. Sixty patients with
      panic disorder and 60 controls with no diagnosis of a mental disorder
      participated in the study. RESULTS: As expected, panic patients showed smaller
      differences in the time needed for classification of panic-related versus non
      panic-related material than controls. CONCLUSIONS: Patients with panic disorder
      show a memory bias for panic-related material when conceptual implicit recall is
      required. In order to clarify whether this bias is involved in the maintenance of
      the disorder, it seems important to investigate whether the bias is still present
      after successful therapy.

PMID- 9556198
TI  - Relationships between alexithymia, emotional control, and quality of life in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Although the constructs of alexithymia and emotional control have
      been associated with physical health, the relationship between these constructs
      is unclear and their influence on health-related quality of life has not been
      investigated previously. This study examined the relationships between
      alexithymia, emotional control, and quality of life in 74 patients with
      inflammatory bowel disease (IBD). METHODS: The subjects completed the 20-item
      Toronto Alexithymia Scale (TAS-20), the Emotional Expression and Control Scale
      (EEC), and the Inflammatory Bowel Disease Questionnaire (IBDQ) for assessing
      quality of life. RESULTS: The TAS-20 correlated negatively and significantly with
      the IBDQ global score and with subscales assessing bowel symptoms, systemic
      symptoms, and emotional functioning; the emotional control subscale of the EEC
      correlated positively and significantly with these measures. Although the TAS-20
      correlated significantly and negatively with the emotional control subscale,
      alexithymia and quality of life scores were unrelated to subscales of the EEC
      assessing tendencies to either hold back or express emotions. A hierarchical
      stepwise multiple regression analysis revealed that alexithymia and, to a lesser
      extent, emotional control play a role in predicting quality of life in patients
      with IBD. CONCLUSIONS: Alexithymia and emotional control are negatively related
      constructs and each construct has an independent influence on the subjective
      health status of patients with IBD.

PMID- 9556199
TI  - Perceived parental attitude, alexithymia and defense style in psychiatric
      outpatients.
AB  - BACKGROUND: Although it is the clinical impression that alexithymia may be due to
      disturbances in the early parent-child relationship and that it is associated
      with primitive defense mechanisms, a possible association with neurotic defense
      mechanisms, such as repression and reaction formation, has also been mentioned.
      However, empirical studies on these and related issues are scarce. The aim of
      this study was to determine the association between perceived parental attitude,
      defense mechanisms and alexithymia. METHODS: In a cross-sectional study we
      obtained data from 78 psychiatric outpatients. Alexithymia, defense mechanisms
      and perceived parental attitude were measured with the Toronto Alexithymia Scale,
      the Defense Style Questionnaire and the Parental Bonding Instrument. RESULTS: We
      found only weak associations between perceived parental attitude and alexithymic
      features. Primitive and adaptive defenses were associated with alexithymic
      features in a clinically sensible way. The strongest association was found
      between primitive defense mechanisms and alexithymic features. There was hardly
      any association between neurotic defense mechanisms and alexithymic features.
      CONCLUSIONS: The results of our study support the hypothesis that alexithymia is
      associated with a primitive defense style, whereas a relation to disturbances in
      early parent-child relationship could not be confirmed. It is argued that
      possibly more severe traumatic experiences, such as physical and sexual abuse,
      than merely a negatively perceived parental attitude, are necessary to develop
      alexithymic features.

PMID- 9556200
TI  - Psychosomatic and psychosocial symptoms are associated with low blood pressure in
      Swedish schoolchildren.
AB  - BACKGROUND: The relation between psychosomatic and psychosocial symptoms and
      blood pressure was studied in Swedish schoolchildren. METHODS: Blood pressure was
      measured in 122 healthy Swedish schoolchildren, aged 6-16 years. Psychosomatic
      and psychosocial symptoms, delinquent behaviour, parental health and employment
      status were assessed. RESULTS: Children with systolic blood pressure above + 1 SD
      of mean reported significantly less symptoms (x = 1.4) than children with blood
      pressure below -1 SD of the mean (x = 2.7; p < 0.05). Children with three or more
      self-reported symptoms had significantly lower blood pressure than children
      without symptoms both in the supine (110 +/- 12 vs. 120 +/- 18 mm Hg; p < 0.05)
      and in the standing position (117 +/- 17 vs. 127 +/- 18 mm Hg; p < 0.05).
      CONCLUSIONS: We conclude that psychosomatic and psychosocial symptoms in children
      might be associated with low blood pressure.

PMID- 9556201
TI  - Need for supportive counselling--the professionals' versus the patients'
      perspective. A survey in a representative sample of 236 melanoma patients.
AB  - BACKGROUND: The aim of the study was to identify melanoma patients who suffered
      significant distress and were judged to be in need of supportive counselling, on
      the one hand, and, on the other, to investigate patient interest in such support.
      METHODS: Out of 236 melanoma patients, who constitute a representative sample of
      melanoma patients in Western Austria, 215 patients participated in the study and
      were assessed with regard to psychosocial distress, coping strategies, social
      networks and interest in receiving psychosocial support. Multiple logistic
      regression analyses were performed with regard to patient interest in receiving
      psychosocial support either from the attending oncologist or from a mental health
      professional. RESULTS: 65 patients (30.2%) experienced moderate and 30 patients
      (14.0%) severe distress, which was predominantly caused by tumour-related fears,
      tension and disturbance of emotional well-being. 83% of the severely distressed
      patients wanted psychosocial support from their oncologists, whereas only half of
      them were interested in additional support from a psychotherapist. In particular,
      patients who showed fear of tumour progression and felt that they were
      insufficiently informed about their disease preferred to consult their
      dermatologist for psychosocial support. On the other hand, patients with poor
      prognosis, receiving only low levels of support from their social network, and
      exhibiting a depressive coping style, showed interest in getting supplementary
      support from a psychotherapist. CONCLUSIONS: These findings underline the
      importance of educating oncologists with a view both to improve their
      communication skills and to help them identify patients making poor adjustment to
      illness in order to offer them appropriate emotional support.

PMID- 9556202
TI  - Psychiatric symptoms and psychological profile of patients with near fatal
      asthma: absence of positive findings.
AB  - BACKGROUND: We examined the presence of psychiatric symptoms and personality
      characteristics in patients with asthma and near fatal asthma (NFA). An NFA
      attack is defined by the presence of one or more of the following symptoms:
      respiratory arrest, alteration in consciousness, need for mechanical ventilation,
      Pa CO2 > 50 mm Hg. METHODS: To assess the relevance of a specific psychiatric
      profile or the difference in personality characteristics existing in patients
      that survived an NFA attack and asthmatic patients. The authors interviewed a
      sample of 17 asthmatic patients who experienced one or more NFA attacks. A
      control group of 17 control patients with asthma who never experienced NFA
      attacks was enrolled. After a baseline assessment, the patients underwent an
      interview concerning their personal and familiar psychiatric history and a
      psychodiagnostic investigation using Hamilton scales for anxiety and depression,
      Zung scales for anxiety and depression, and Minnesota Multiphasic Personality
      Inventory. The study was performed in a 6-month period. RESULTS: No significant
      differences in the results of psychodiagnostic tests between NFA patients and the
      control group were reported. Psychiatric history was similar in the two groups.
      CONCLUSIONS: Our results suggest that psychiatric symptoms and personality
      characteristics are not related to the presence of asthma with or without NFA.

PMID- 9556203
TI  - Isolation and characterization of CspBI, a novel NotI isoschizomer from
      Corynebacterium species B recognizing 5'-GC/GGCCGC-3'.
AB  - Sixty-seven bacterial strains were surveyed for the presence of type II
      restriction endonucleases, especially concerning super-rare-cutting enzymes.
      Fourteen strains were found to contain specific enzymes. One of them CspBI from
      Corynebacterium species B was purified and characterized as an isoschizomer of
      NotI, which recognizes the palindromic octanucleotide sequence 5'-GC/GGCCGC-3'
      and cleaves at the position shown by the arrow. A comparison between the cleavage
      patterns on different DNAs, obtained with partially purified endonucleases from
      other detected producents including some strains of Corynebacterium, Cellulomonas
      and Rhizobium has shown that these enzymes do not belong to super-rare-cutting
      restriction endonucleases.

PMID- 9556205
TI  - Midkine induces histamine release from mast cells and the immediate cutaneous
      response.
AB  - Midkine is a product of a retinoic acid-responsive gene and exerts a variety of
      biological activities. The aim of our investigation is to determine whether human
      midkine have histamine-releasing effects on mast cells, and to show the evidence
      of the inflammation induced by midkine. Midkine induced histamine release from
      rat peritoneal mast cells with a rapid response in a dose-dependent manner.
      Extracellular calcium inhibited the histamine release induced by midkine in a
      dose-dependent manner. Pertussis toxin and benzalkonium chloride inhibited the
      histamine release induced by midkine. Gi-proteins exert an effect on the
      histamine release of midkine. The immediate cutaneous response induced by midkine
      was positive. These results suggest that midkine may take part in some
      inflammation via histamine release from mast cells.

PMID- 9556204
TI  - Differential expression of multidrug resistance (mdr) and canalicular
      multispecific organic anion transporter (cMOAT) genes following extrahepatic
      biliary obstruction in rats.
AB  - The hepatic canalicular membrane has transporters that play an important role as
      efflux pumps in the excretion of endogenous bile constituents or xenobiotics into
      bile canaliculi. To elucidate functional significance of canalicular transporters
      in the mechanism of cholestasis, mRNA expression levels of multidrug resistance
      (mdr) 1b, mdr2 and canalicular multispecific organic anion transporter (cMOAT)
      genes were analyzed by Southern blotting of reverse-transcribed PCR products of
      liver mRNA obtained from cholestatic rats that had been subjected to bile duct
      ligation. Both mdr1b and mdr2 mRNA expression increased after ligation.
      Immunohistochemical study revealed that the products of both mdr1b and mdr2 were
      present on the canaliculi, and that their levels increased after ligation. In
      contrast, cMOAT mRNA expression was not increased, but rather attenuated by
      ligation. The expression of canalicular transporters was differentially regulated
      in extrahepatic biliary obstruction, indicating the different roles are played by
      mdr and cMOAT in the pathogenesis of cholestasis.

PMID- 9556206
TI  - Cross-linking induces homodimer formation and inhibits enzymatic activity of
      chicken stomach ecto-apyrase.
AB  - We have investigated the effect of cross-linking on the enzymatic activity and
      oligomer formation of the chicken stomach ecto-apyrase. Cross-linking with the
      hydrophobic, lysine-specific dithiobis(succinimidylpropionate) (DSP) caused equal
      inhibition of ATPase and ADPase activity in both the membrane-bound and detergent
      solubilized ecto-apyrase. The inhibitory effect of cross-linking was reversed
      upon the addition of the reductant dithiothreitol. Western blots of aliquots of
      the cross-linked samples show decreased amounts of the monomeric 80 kDa ecto
      apyrase and the appearance of a 160 kDa dimer under conditions inducing enzyme
      inhibition. Therefore, the chicken stomach ecto-apyrase, like the chicken gizzard
      ecto-ATPase, is likely a homodimer in vivo. Unlike the related gizzard ecto
      ATPase, however, the native stomach ecto-apyrase is not stimulated, but rather
      inhibited by cross-linking, presumably due to different quaternary structural
      stability of the two enzymes.

PMID- 9556207
TI  - Detection of transmembrane helical segments at the nucleotide level in eukaryotic
      membrane protein genes.
AB  - The analysis of base distributions at the three codon positions, in sequences
      coding for polytopic membrane proteins from Eukaryotes, reveals a global excess
      of thymine and a depletion of adenine, at the second codon position. These genes
      were scanned using a sliding window, in which the average ratio of T over A at
      the second position of codons was computed. The scan shows that sharp peaks of
      this ratio, which are responsible for the high mean value of this parameter in
      the genes, correlate closely with the transmembrane segments of the membrane
      proteins. These results are quite similar to our previous findings for bacterial
      polytopic inner membrane proteins. This establishes the ratio of T over A at
      codon position two as a universal parameter for both the characterization of the
      genes of polytopic membrane proteins, and for the location of alpha-helical,
      transmembrane segments of these proteins.

PMID- 9556208
TI  - Induction of fructose 1,6-bisphosphatase in HL-60 leukemia cells by retinoic
      acid.
AB  - The expression of the fructose 1,6-bisphosphatase gene in HL-60 cells was induced
      by retinoic acid. The levels of mRNA, enzyme activity and enzyme protein in the
      cell line began to rapidly increase after culturing with retinoic acid for 72 h.
      Retinoic acid dose-dependently increased the enzyme activity with maximal
      stimulation at 1 microM. The responses of the fructose 1,6-bisphosphatase gene
      expression by retinoic acid were markedly slower than those of the enzyme
      expression by 1alpha,25-dihydroxyvitamin D3. When HL-60 cells were cultured in
      the presence of both retinoic acid and 1alpha,25-dihydroxyvitamin D3, the effects
      of the two agents on enzyme activity, protein and mRNA were additive.

PMID- 9556209
TI  - Different effects of cell-permeable ceramide analogs on platelet activation.
AB  - The effects of cell-permeable ceramide analogs on platelet responses induced by
      agonists were investigated. When washed rabbit platelets were pretreated with
      ceramide and then stimulated with thrombin or U46619, C2-ceramide (N
      acetylsphingosine) dose-dependently inhibited the aggregation and arachidonic
      acid liberation, whereas C6-ceramide (N-hexanoylsphingosine) and C8-ceramide (N
      octanoylsphingosine) enhanced these responses. Furthermore, C6-ceramide, but not
      C2-ceramide, enhanced the increase in and prevented the progressive decrease in
      cytoplasmic free Ca2+ concentration induced by U46619. On the other hand,
      treatment with sphingomyelinase potentiated the aggregation in response to
      U46619. These results indicate that the effects of cell-permeable ceramide
      analogs on platelet activation vary with N-acyl chain length.

PMID- 9556211
TI  - Effects of deleting A19 tyrosine from insulin.
AB  - A mutant proinsulin gene was constructed through PCR mediated mutagenesis. The
      code of A19Tyr was deleted. The mutant proinsulin, (deltaY)19-lys-proinsulin
      [(deltaY)19KPI], was expressed in E. coli and purified. After treatment with
      trypsin and carboxypeptidase B, and Resource Q separation, (deltaY)19-human
      insulin [(deltaY)19HI] was obtained. It retains 63.6% of receptor binding
      activity but only 2.2% of immune activity, and shows a longer retaining time on
      reverse-phase FPLC and a slower mobility by native PAGE analysis. These results
      suggest that the deletion of A19Tyr causes some conformational changes on
      insulin, which plays a minor role on the affinity of insulin to its receptor, and
      a major role on immunogenicity of the hormone.

PMID- 9556210
TI  - Lithium regulation of protein phosphorylation in rat cerebral cortex slices in
      vitro.
AB  - The aim of the present study was to evaluate the direct effect of Li+ and Na+-Li+
      exchange on protein phosphorylation in rat cerebral cortex slices incubated in
      Krebs Ringer medium. When Na+ concentration was varied in the incubation medium,
      either by replacement with Li+ or sucrose, a variable effect on [32P] phosphate
      incorporation into proteins was observed. Protein phosphorylation in cerebral
      cortex slices was very low in the absence of Na+, and some dependence of
      phosphorylating system of neural tissue on extra cellular concentration of Na+
      was evident. Lithium was not able to replace sodium as far as protein
      phosphorylation in cortical slices is concerned. Ouabain was more effective in a
      Li+ containing medium in inhibiting protein phosphorylation, presumably due to
      improper functioning of the sodium pump.

PMID- 9556212
TI  - Short-term effect of dexamethasone on fatty acid and cholesterol synthesis in
      isolated rat hepatocytes.
AB  - The short-term effect of dexamethasone, a synthetic glucocorticoid, on both fatty
      acid and cholesterol synthesis has been investigated in rat hepatocyte cultures.
      Within 4h following hormone addition to the cultures, a noticeable stimulation of
      labelled acetate incorporation into fatty acids was observed. Similar behaviour
      was noticed when [3H]H2O was used as an independent index of the lipogenic
      activity. In the same cultures, however, cholesterol synthesis from both
      [14C]acetate or [3H]H2O was significantly reduced by dexamethasone addition. In
      these conditions, no significative variation of cholesterol synthesis starting
      from labelled mevalonate was observed.

PMID- 9556213
TI  - Down-regulation of protein kinase C-alpha detected in human colorectal cancer.
AB  - The down-regulation of protein kinase C (PKC) was examined by Western blot
      procedure on about 30 tissue samples derived from human colorectal cancer and the
      corresponding normal mucosa. PKC-alpha down-regulation was detected in 60% of the
      cancer tissues compared with the respective normal mucosa and was observed in a
      higher frequency with the tissues under more advanced cancer stages. However, the
      frequencies of the down-regulation of PKC-delta and PKC-zeta were lower than that
      of PKC-alpha. These results suggest that a decreased level of PKC-alpha may
      affect the cell growth and tumor promotion in colorectal tissue.

PMID- 9556215
TI  - Carbohydrates regulate the dimerization of angiotensin-converting enzyme.
AB  - Regulation of the catalytic activity and supramolecular structure of angiotensin
      converting enzyme was studied in reverse micelles of Aerosol OT in octane as
      biomembrane model. The kinetic experiments and the sedimentation analysis
      demonstrated that the enzyme can function both in monomeric and dimeric form. The
      degree of dimerization was strongly dependent on the concentration and structure
      of mono- and disaccharides added to the media, indicating the specific role of
      carbohydrates in forming the supramolecular structure of angiotensin-converting
      enzyme. The existence of carbohydrate-binding center on the enzyme molecule is
      proposed.

PMID- 9556214
TI  - Structural factors affect the interactions of anticardiotoxin antibodies and
      cobra venom cardiotoxins.
AB  - Two antibody preparations against cardiotoxins were raised by immunizing rabbits
      with cardiotoxin 1 and cardiotoxin 3, respectively. The two antibody preparations
      showed precipitin reactions with cardiotoxins 1, 2, 3 and 5, respectively.
      However, the results of competitive enzyme-linked immunoassay revealed that the
      respective cardiotoxin molecules exhibited different reactivity toward
      anticardiotoxin antibodies. Moreover, the order of reactivity with antibodies was
      not in line with the degree of their sequence identity. This suggest that the
      anticardiotoxin antibodies may recognize conformational epitopes rather than
      sequential ones in the toxin molecules. Alternatively, the four cardiotoxins
      reacted well with the antibodies in the absence of competitor, suggesting that
      sequence variations with cardiotoxin molecules may not exclusively influence the
      potential use of the anticardiotoxin antibodies for the neutralization of the
      activity of cardiotoxin variants.

PMID- 9556216
TI  - Saccharide-assisted delivery of cytotoxic liposomes to human malignant cells.
AB  - The overexpression of lectins by malignant cells was applied for in vitro
      targeting of liposomes equipped with a saccharide vector and loaded in the lipid
      phase with a lipid derivative of anticancer agent sarcolysine. The lectin
      specificity of human leukemia HL-60 and human lung adenocarcinoma ACL cells was
      revealed by tests with fluorescein-labeled sugar probes. With the help of
      fluorescent lipid dye it was shown that active saccharide ligands increased the
      level of the vectored liposome binding to malignant cells by 50-80% as compared
      to liposomes without vector or with inactive one. The degree of liposome/cell
      membrane fusion was monitored fluorometrically and was shown to be complete and
      independent of the vectors. The targeted drug-loaded liposomes had the cytotoxic
      activity 2-4 times higher as compared to the vector-free ones.

PMID- 9556217
TI  - Characterization of extracellular menadion-catalyzed H2O2 production by NIH/3T3
      cells.
AB  - The extracellular menadione-catalyzed H2O2 production by NIH/3T3 cells was
      expected to depend on plasma membrane-bound NAD(P)H:quinone oxidoreductase. This
      enzyme was estimated to be a flavoprotein with the molecular mass of 70 KDa. Km
      values of plasma membrane-bound NAD(P)H:quinone oxidoreductase producing H2O2
      were 60 microM for NADH and 150 microM for NADPH. Ca2+ ionophore A23187
      controlled menadione-catalyzed H2O2 production by the cells in time- and
      concentration-dependent manner.

PMID- 9556218
TI  - Investigation of the yeast mitochondrial unselective channel in intact and
      permeabilized spheroplasts.
AB  - The existence of an activity corresponding to the nucleotide-induced Yeast
      Mitochondria Unselective Channel (YMUC2) of isolated mitochondria was
      investigated in permeabilized and intact spheroplasts of the baker's yeast Yeast
      Foam. In nystatin-permeabilized spheroplasts, ATP and GDP-beta-S induced a
      decavanadate-sensitive stimulation of the respiration only under conditions
      equivalent to those previously reported for isolated mitochondria (low phosphate
      concentration, presence of a salt). On intact spheroplasts parallel measurements
      of respiration rate, [ATP]/[ADP] ratio and mitochondrial transmembrane potential
      allowed to show that the addition of the glucose analog 2-deoxyglucose decreased
      the permeability of the inner mitochondrial membrane owing to cellular ATP
      depletion. This strongly supports the hypothesis that Yeast Mitochondria
      Unspecific Channel is active in situ and inhibited by cellular [ATP] depletion.

PMID- 9556219
TI  - Activation of red blood cell glutathione peroxidase and morphological
      transformation of erythrocytes under the action of tert-butyl hydroperoxide.
AB  - Susceptibility of control and diabetic erythrocytes to oxidative stress was
      measured after incubation with various concentration of tert-butyl hydroperoxide
      (t-BHP). TBA-reactive substances (TBARS) formed were determined by the method of
      Stocks & Dormady modified by Jain. GSH and total glutathione were estimated by
      the procedure of Ellman and Akerboom and Sies. Activity of GSH peroxidase was
      determined by the method of Martinez et al. Protein SH groups were determined
      after membrane isolation by the method of Dodge et al. Cell morphology was viewed
      under phase contrast microscope with a magnification of 500x. All results were
      analyzed by the unpaired two tailed Student's t-test. Oxidative treatment of
      erythrocytes with tert-butyl hydroperoxide significantly increases the reaction
      rate but decreases the affinity for substrate (tert-butyl hydroperoxide). The
      susceptibility of the enzyme from diabetic erythrocytes to oxidation is higher in
      comparison with normal cells. The oxidation of cellular reduced glutathione (GSH)
      is not correlated with oxidation of membranous protein SH-groups. Oxidative
      damage of erythrocytes induces significant cell morphological transformations.

PMID- 9556220
TI  - A sequence highly similar to PNG is located on chromosome 22q12 in intron 15 of
      the LIMK-2 gene.
AB  - In this report we describe a sequence (PNG22) highly similar to the Phospholipase
      C beta3 Neighboring Gene (PNG). We also report that PNG22 is located in the q12
      region on chromosome 22 between markers D22S1144 and D22S280. This finding
      explains that PNG probes cross hybridize to sequences on chromosome 22. Fine
      mapping using our sequence data and the complete sequence of a PAC clone
      (DJ515N1), located in this region, determined that PNG22 is located in intron 15
      of the LIMK-2 gene. PNG22 is 93% homologous to PNG, however it do not have the
      introns described for the PNG gene, instead matching the cDNA sequence. This
      leads us to suggest that PNG22 probably represents a PNG pseudogene. In this
      report we also list the exon intron borders and the genomic structure of LIMK-2
      and place it on the Sanger Center chromosome 22 Physical map. It also explains
      the finding that PNG probes cross hybridize to sequences on chromosome 22.

PMID- 9556221
TI  - Absorption and fluorescence spectra of polyene antibiotics in the presence of
      human serum albumin.
AB  - The alteration in the fluorescence spectra observed for the polyene antibiotics:
      nystatin and amphotericin B in the presence of human serum albumin is due to a
      decrease in the polar character of the antibiotic environment when these are
      bound to the protein. Amphotericin B showed two types of binding sites, the first
      having very high affinity (5.8 10(7) M(-1]) and a secondary binding site with an
      affinity one order lower than the primary sites. This secondary binding site was
      very sensitive to temperature change. Nystatin yielded only one type of binding
      sites with an affinity of 1.1 10(6) M(-1). An electrostatic component was found
      in the binding of both ligands, as well as an important disorder at the protein
      binding sites. However the secondary binding site for AMP showed negative
      entropic change value, which suggests different mechanism of binding respect to
      the primary one. Conformational change induced by the temperature in the albumin
      molecule was detected by nystatin binding. Fatty acids produced an interference
      in the binding of both antibiotics to albumin.

PMID- 9556222
TI  - Genetic variants of chicken erythrocyte histone H5.
AB  - Two allelic electromorphs a and b of chicken erythrocyte histone H5 have been
      detected in a sodium dodecyl sulfate polyacrylamide gel. In an acid-urea gel,
      however, each of the allelic variants was found to be accompanied by a slower
      migrating form. A comparison of alpha-chymotrypsin-digested products of H5.a and
      H5.b revealed that they differed in N-terminal domains. The H5 variants were
      distributed differently not only in various chicken races but also in distinct
      lines within a breed. Allele H5b was about 2.6-4.6 as abundant as its counterpart
      H5a in most chicken populations examined. These proportions were distorted in two
      Leghorn lines: the ratio of H5b to H5a was only 1.6 in line H22 and increased up
      to 32 in line G99.

PMID- 9556223
TI  - Inosine-5'-monophosphate analogues as inhibitors of human IMP cyclohydrolase and
      cellular growth.
AB  - The catalytic mechanism for the enzyme, IMP cyclohydrolase, may involve a
      reaction intermediate with negative charge in the 2-position of the purine ring
      (Szabados, E., Hindmarsh, E., Phillips, L., Duggleby, R.G. & Christopherson, R.I.
      (1994) Biochemistry 33, 14237-14245). Three analogues of IMP have been
      synthesised where fluorine, chlorine or bromine has been substituted in the 2
      position on the purine ring. These analogues with an electronegative substituent
      may resemble a reaction intermediate for IMP cyclohydrolase; 2-fluoro IMP is a
      potent inhibitor of the enzyme with a Ki value of 0.19 microM, while 2-chloro IMP
      has a Ki of 1.9 microM and 2-bromo IMP is not inhibitory. However, IMP
      cyclohydrolase is not inhibited in human CCRF-CEM leukaemia cells exposed to 2
      fluoro inosine although it is toxic to these cells with an IC50 value of 4.9
      microM.

PMID- 9556224
TI  - Esterification of D-mannoheptulose confers to the heptose inhibitory action on D
      glucose metabolism in parotid cells.
AB  - D-mannoheptulose, but not its hexaacetate ester, inhibits, in a competitive
      manner, D-glucose phosphorylation by either purified beef heart hexokinase or
      crude parotid gland homogenates. Yet, D-mannoheptulose hexaacetate, but neither
      the unesterified heptose nor acetate or its methyl ester, inhibits D-[5
      3H]glucose utilization and D-[U-14C]glucose conversion to 14CO2 and 14C-labelled
      acidic metabolites and amino acids in intact isolated parotid cells. It is
      proposed, therefore, that D-mannoheptulose hexaacetate crosses efficiently the
      plasma membrane of parotid cells and, after intracellular hydrolysis, allows
      inhibition of D-glucose phosphorylation by the unesterified heptose. The ester of
      D-mannoheptulose could thus represent a useful tool to inhibit hexose
      phosphorylation and interfere with cell growth in cells otherwise resistant to
      the heptose.

PMID- 9556225
TI  - Protective role of superoxide dismutase in iron toxicity in yeast.
AB  - It has been found that yeast mutants deficient in cytosolic superoxide dismutase
      CuZnSOD are hypersensitive to ferrous iron. In contrast mutants that are
      deficient in catalases and cytochrome c peroxidase do not differ from the
      standard strain in this respect. These findings suggest that iron toxicity may
      depend on the redox status of the cell. They also shed light on the role of
      superoxide dismutases in preventing the toxic effects of oxygen.

PMID- 9556226
TI  - The role of cationic amino acid residues in the lethal activity of stonustoxin
      from stonefish (Synanceja horrida) venom.
AB  - Stonustoxin (SNTX) is a two subunit pore-forming cytolytic protein purified from
      the venom of the stonefish (Synanceja horrida). SNTX also possesses lethal
      activity. Since cationic residues contribute significantly to the cytolytic
      activity of several pore-forming toxins, we examined the role of lysine and
      arginine residues in the lethal activity of SNTX. SNTX lost its lethal activity
      when the positively-charged side chains of lysine residues were converted to
      negatively-charged side chains upon succinylation. When the arginine residues
      were modified using 2,3-butanedione, SNTX also lost its lethal activity. However,
      the domains for cytolytic and lethal activity may not necessarily be the same.

PMID- 9556227
TI  - The in vitro effect of ridogrel on platelet function in normocholesterolaemic and
      familial hypercholesterolaemic type IIa subjects.
AB  - Platelets from familial hypercholesterolaemia type IIa patients are hyperreactive
      and produce increased amounts of thromboxane A2. These modifications of platelet
      function may play an important role in the occurrence of premature
      atherosclerosis. One approach to the prevention of the thromboembolic
      complications of atherosclerosis is the use of antiplatelet agents which depress
      platelet function. Ridogrel, a combined thromboxane synthase inhibitor and
      thromboxane A2/prostaglandin endoperoxide receptor blocker inhibits platelet
      aggregation. This study was designed to investigate the in vitro effect of
      ridogrel on platelet function in normocholesterolaemic and familial
      hypercholesterolaemia type IIa subjects. In citrated platelet rich plasma
      ridogrel significantly inhibited platelet aggregation and thromboxane A2
      production in response to collagen, ADP and arachidonic acid stimulation. In
      washed platelets ridogrel significantly decreased aggregation and serotonin
      release. Ridogrel significantly increased cAMP levels in response to thrombin
      stimulation. In conclusion, ridogrel at low concentrations significantly
      inhibited the in vitro function of platelets in a dose dependant manner in both
      normocholesterolaemic subjects and familial hypercholesterolaemia IIa subjects.

PMID- 9556228
TI  - Prevalence of activated protein C resistance in the Chinese population.
AB  - In 1996, a total of 1700 subjects, including 461 healthy subjects and 1239 clinic
      patients, were randomized and consecutively entered into our study. Their mean
      age was 49.30+/-18.71 years, range 1-99 years. Of them, 1117 were male, and 583
      were female. The mean age of the male was 42.96+/-17.64 years, and of the female,
      52.60+/-18.41 years. The mean activated protein C ratio in 1700 subjects was
      2.96+/-0.69, range 2.00-7.93. None of them had activated protein C ratio <2.0.
      The mean activated protein C ratio in the male was 2.81+/-0.63, and in the female
      was 3.04+/-0.71. None of the subjects was found to have activated protein C
      resistance. DNA analysis for the Arg 506-Gln mutation was also performed on 492
      out of the 1700 subjects; none of them had this mutation. We suggested that the
      Chinese is not a race with the trait of activated protein C resistance.

PMID- 9556229
TI  - Clinical evaluation of an immunoturbidimetric D-dimer assay in the diagnostic
      procedure of deep vein thrombosis and pulmonary embolism.
AB  - We investigated 128 patients with suspected deep vein thrombosis and 26 patients
      with suspected pulmonary embolism. Plasma cross-linked fibrin degradation
      products were measured instantly by a new rapid and fully quantitative
      immunoturbidimetric assay (Boehringer Mannheim) which recognizes the D-dimer
      epitope by antibody-coated latex particles. Diagnosis of deep vein thrombosis was
      established by either ascending venography (n = 105) or colour duplex ultrasound
      (n = 8), whereas for the exclusion of deep vein thrombosis only venography was
      accepted. The sensitivity/specificity for the diagnosis of deep vein thrombosis
      was 98%/44%. Patients with suspected pulmonary embolism were examined by
      pulmonary angiography (n = 19) or perfusion lung scanning alone (n = 6), if
      sufficient. One pulmonary embolism was diagnosed at post-mortem examination. For
      pulmonary embolism, sensitivity/specificity was 100%/50%. These findings indicate
      that the new immunoturbidimetric technique is as reliable as former ELISA methods
      and allows to rule out thromboembolic disorders. D-dimers showed a correlation to
      the extent of the deep vein thrombosis, proximal thrombosis producing higher D
      dimer levels. Patients presenting immediately after the onset of symptoms were
      found to have higher D-dimers than patients examined after a few days. A
      quantitative D-dimer measurement thus seems to provide precious additional
      information of the duration and the extent of thromboembolic disease.

PMID- 9556230
TI  - Production of a recombinant antithrombotic and fibrinolytic protein, PLATSAK, in
      Escherichia coli.
AB  - The three main components involved in thrombosis and haemostasis are thrombin,
      platelets, and plasmin. Almost all inhibitors of thrombosis are focused either on
      the inhibition of thrombin or on the inhibition of platelets. We designed a
      construct using the fibrinolytic activity of staphylokinase, fused via a
      cleavable linker to an antithrombotic peptide of 29 amino acids. The peptide was
      designed to include three inhibitory regions: (1) the Arg-Gly-Asp (RGD) amino
      acid sequence to prevent fibrinogen binding to platelets; (2) a part of
      fibrinopeptide A, an inhibitor of thrombin; and (3) the tail of hirudin, a potent
      direct antithrombin. The amino acid sequence of the 29 amino acid peptide was
      reverse translated, and the gene was chemically synthesised and cloned into an
      expression vector as a 3' fusion to the staphylokinase gene. Gene expression was
      induced in E. coli Top 10 cells and the fusion protein, designated PLATSAK, was
      purified using metal affinity chromatography. The purified fusion protein
      significantly lengthened the activated partial thromboplastin time and thrombin
      time and inhibited the amidolytic activity of thrombin. The fibrinolytic activity
      was almost equal to that of recombinant staphylokinase as measured with a
      thrombelastograph. Platelet aggregation was not markedly inhibited by PLATSAK,
      probably due to the unfavourable three dimensional structure, with the Arg-Gly
      Asp sequence buried inside. Our results confirm that it is feasible to design and
      produce a hybrid multifunctional protein that targets various components of the
      haemostatic process.

PMID- 9556231
TI  - Expanded polytetrafluoroethylene (ePTFE) vascular graft loses its thrombogenicity
      six months after implantation.
AB  - Although expanded polytetrafluoroethylene (ePTFE) has been believed to be an
      inert material for vascular prosthesis, it shows less tendency of graft
      maturation by means of endothelialization. The aim of this study is to evaluate
      long-term alteration in thrombogenicity of ePTFE grafts after implantation.
      Serial levels of thrombin-antithrombin III complex (TAT), D-dimer, C-reactive
      protein (CRP), and prothrombin time (PT) were examined in 77 patients following
      ePTFE Y-graft implantation for up to five years. TAT showed biphasic elevation
      after implantation; TAT increased from 16.4+/-8.6 ng/ml to 27.4+/-10.5 ng/ml at
      one day, decreased to 18.5+/-4.5 ng/ml at one week, and increased again to 25.3+/
      8.5 ng/ml at two weeks. Elevated TAT gradually decreased after the second peak to
      reach a lower level than that before surgery after six months. There was no
      significant difference in TAT level after six months due to the difference in
      diagnosis or anti-thrombotic therapy. We suggest that ePTFE grafts lose their
      thrombogenicity six months after implantation, after which anti-thrombotic
      therapy might be unnecessary.

PMID- 9556232
TI  - Action of neurotransmitters: acetylcholine, serotonin, and adrenaline in an
      experimental arterial thrombosis induced by oxygen free radicals.
AB  - It is well known that high stress and particularly an enhancement of plasma
      catecholamines and myocardial infarction have a close relation. In addition,
      adrenaline is presented as a prothrombogenic agent in vivo. The role of the other
      agents such as serotonin or acetylcholine, in the development of arterial
      thrombosis is somewhat uncertain, although, the role of each of them is often
      considered at the level of vascular regulation only. Therefore, the present study
      was designed to investigate the effects of three neurotransmitters on
      experimental arterial thrombosis model induced by generation of free radicals.
      The results demonstrate that intravenously injection of adrenaline or serotonin
      (1 ng/kg) stimulated arterial thrombosis formation, whereas injection of high
      dose of acetylcholine (5 mg/kg) slackened the thrombosis formation.

PMID- 9556233
TI  - An improved method for the detection of the G20210A transition in the prothrombin
      gene.

PMID- 9556234
TI  - A polymorphic cluster in the 5' region of the human coagulation factor VII gene:
      detection, frequency, and linkage disequilibrium.

PMID- 9556235
TI  - Effects of pneumoperitoneum on tumor implantation with decreasing tumor inoculum.
AB  - INTRODUCTION: The aim of this study was to determine the effect of
      pneumoperitoneum on the rate of trocar-site implantation with decreasing inoculum
      of cancer cells. METHODS: A total of 0.5 ml of GW-39 human colon cancer cell
      suspensions at 1 percent (approximately 3.2 x 10(5) cells) and at 0.5 percent
      (approximately 1.6 x 10(5) cells; v/v) were injected into the abdomen of hamsters
      through a midline incision. Animals in each group were randomized to receive
      either pneumoperitoneum (1 percent = 33; 0.5 percent = 43) or not (1 percent =
      32; 0.5 percent = 39). Gross and microscopic tumor implants were documented seven
      weeks later at four trocar sites. RESULTS: In the 1 percent group,
      pneumoperitoneum significantly increased trocar-site tumor implants from 50 to 71
      percent (P < 0.001). Pneumoperitoneum also resulted in the following: 1) more
      frequent involvement of all four concurrent sites (38 vs. 10 percent; P < 0.02);
      2) more frequent palpable tumors (13 vs. 5 percent; P < 0.01); 3) larger tumor
      mass (2.1 +/- 0.6 g vs. 0.2 +/- 0.1 g; P < 0.02). In the 0.5 percent group,
      pneumoperitoneum did not significantly increase trocar-site tumor implants, and
      it did not result in a larger tumor mass. The percent increase in trocar-site
      implants owing to pneumoperitoneum was influenced by the amount of tumor inoculum
      (21 percent in the 1 percent group; 10 percent in the 0.5 percent group). The
      mass of palpable tumor implants after pneumoperitoneum decreased with decreased
      inoculum: 1 percent = 2.1 +/- 0.6 g; 0.5 percent = 0.3 +/- 0.1 g (P < 0.0001).
      CONCLUSIONS: Pneumoperitoneum significantly increased both tumor implantation
      rate and mass when approximately 3.2 x 10(5) colon cancer cells were injected
      into the peritoneal cavity. These effects of pneumoperitoneum diminished with one
      half as many tumor cells injected in the peritoneal cavity.

PMID- 9556236
TI  - Decision-making in rectal cancer surgery: survey of North American colorectal
      residency programs.
AB  - PURPOSE: Although rectal cancer is common in the United States, there is
      significant variation in management and outcome of this disease. The aim of this
      study is to measure the amount of variability that exists in the way colorectal
      surgeons investigate and manage patients with rectal cancer. METHODS: A detailed
      questionnaire covering preoperative assessment, operative technique, and follow
      up of primary rectal cancer was sent to all colorectal surgeons associated with
      colorectal residency programs throughout North America. RESULTS: One hundred ten
      responses were obtained (response rate, 71 percent). Surgeons were in broad
      agreement (>75 percent agree) on the routine preoperative use of endorectal
      ultrasound and carcinoembryonic antigen and the postoperative use of endorectal
      ultrasound. There was also broad agreement about the use of adjuvant therapy and
      radical resection for a poorly differentiated uT2,N0 cancer, the use of total
      mesorectal excision for a mid rectal cancer, and for the choice of loop ileostomy
      if diversion is necessary. Two-thirds of the surgeons used adjuvant therapy and
      radical resection for a uT3,N0 cancer and preferred a follow-up schedule of three
      monthly visits for two years with six monthly visits for the next three years.
      Opinion was divided (<63 percent agreement) on the use of a preoperative liver
      scan, the approach to a moderately differentiated uT2,N0 cancer, the use of
      rectal irrigation before resection, the timing of colonoscopy in a patient with
      stenosing rectal cancer, and the frequency of postoperative colonoscopies.
      CONCLUSIONS: There is considerable variation in the management of low rectal
      cancer advocated by colorectal surgeon educators. For each histologic and
      pathologic stage, opinion is divided about which operation is best. Careful
      outcomes analysis is required to clarify the situation.

PMID- 9556237
TI  - Mechanical, histologic, and biochemical effects of canine rectal formalin
      instillation.
AB  - Instillation of 4 percent formalin effectively treats radiation hemorrhagic
      proctitis; however, little is known regarding its side effects. PURPOSE: The
      study contained herein was undertaken to determine rectal compliance and collagen
      content, mucosal and vascular histologic changes, and kinetics of formalin
      absorption following instillation. METHODS: Fifteen mongrel dogs (50-60 pounds)
      were randomized into five experimental groups according to time elapsed from
      formalin treatment: control, acute, one week, two weeks, and four weeks. Formalin
      was instilled in 30-ml aliquots to a total volume of 400 ml. Rectal compliance
      (closed manometry system) was assessed pre-formalin and post-formalin at the
      designated time interval. Serum formalin metabolites were determined at time 0,
      0.5, 1, and 3 hours. A segment of rectal wall was analyzed for collagen content,
      mucosal injury, and blood vessel density. RESULTS: Serum formalin levels peaked
      within 30 minutes, returning to normal by 3 hours. With the exception of one dog,
      toxic levels were not reached at any time during the study. No dogs experienced
      sepsis, fever, or altered gastrointestinal function. Acute and one-week dogs
      showed mild diffuse proctitis and mucosal slough, which healed within two weeks.
      Rectal compliance and collagen content were unchanged. Mucosal blood vessels
      decreased in number early (P = 0.03). CONCLUSIONS: Instillation of 4 percent
      formalin in sequential aliquots of a small volume that is kept in contact for a
      short period of time is safe. Serum formalin levels generally do not reach toxic
      levels, and the slight elevation in formalin concentration that was seen returns
      to normal within three hours. Formalin-induced proctitis heals within two weeks,
      and no long-term changes in rectal compliance or collagen content were seen.

PMID- 9556238
TI  - Surgical treatment of piles: prospective, randomized study of Parks vs. Milligan
      Morgan hemorrhoidectomy.
AB  - PURPOSE: The present prospective, randomized clinical trial compares the outcome
      of surgical hemorrhoidectomy according to Parks and Milligan-Morgan in terms of
      hospital stay, duration of incapacity to work, symptom relief, length of
      morbidity, and patient convenience. METHODS: Thirty-four consecutive patients
      with third or fourth degree internal hemorrhoids were randomly allocated to the
      two groups. Before surgery, all patients were interviewed using a standard
      questionnaire, followed by rectal examination. All patients underwent a follow-up
      interview and examinations 1, 2, 4, 8, and 12 weeks after the operation. RESULTS:
      No serious postoperative complications were seen. Length of hospital stay (3.2
      days for Parks hemorrhoidectomy vs. 4.6 days for Milligan-Morgan
      hemorrhoidectomy; 95 percent confidence interval, 0.2 and 2.6, respectively; P =
      0.02) and mean duration of incapacity to work (12.3 days for Parks
      hemorrhoidectomy vs. 20.2 days for Milligan-Morgan hemorrhoidectomy; 95 percent
      confidence interval, 5.7 and 10.2, respectively; P < 0.001) differed
      significantly between the Milligan-Morgan and Parks patients. Until two weeks
      after the operation, Milligan-Morgan hemorrhoidectomy patients experienced
      significantly more pain. CONCLUSIONS: Our study confirms that both operations are
      safe, easy to perform, and lead to satisfactory results. However, the Parks
      procedure is the preferred option, because it minimizes patients' postoperative
      discomfort, is more economic, has a significantly reduced hospital stay, and has
      a shorter time for return to work.

PMID- 9556239
TI  - Results from pelvic exenteration for locally advanced colorectal cancer with
      lymph node metastases.
AB  - PURPOSE: We examined the survival benefit of pelvic exenteration for locally
      advanced colorectal cancer with lymph node metastases, because this issue remains
      controversial. METHODS: Medical records of 50 patients who underwent curative
      pelvic exenteration for colorectal cancer were reviewed retrospectively. Nodal
      metastases were examined by the clearing method in 29 patients and by the
      conventional manual method in 21 patients. RESULTS: Invasion to contiguous pelvic
      organs was present in 40 patients (80 percent) and absent in 10 patients (20
      percent). Node metastases were present in 33 patients (66 percent). Operative
      morbidity and mortality rates were 22 percent (11 patients) and 6 percent (3
      patients), respectively. Respective five-year survival rates were 60 and 80
      percent in the groups with and without organ invasion (no significant
      difference). Five-year survival rates in patients with nodal metastases was 54.6
      percent but was significantly higher, 82.4 percent, in patients without nodal
      metastases. Five-year survival in 28 patients with both organ invasion and nodal
      metastases was 53.6 percent. CONCLUSIONS: Long-term survival was afforded by
      pelvic exenteration for locally advanced colorectal cancer with nodal metastases.

PMID- 9556240
TI  - New method of radiotherapy for anal cancer with three-dimensional tumor
      reconstruction based on endoanal ultrasound and ultrasound-guided afterloading
      therapy.
AB  - PURPOSE: Standard treatment of anal cancer is a protocol of combined chemotherapy
      and percutaneous radiotherapy. We developed a new endosonography-based radiation
      target simulation method, because endoanal sonography gives the best opportunity
      to stage the tumor accurately. Based on this method, an afterloading needle
      application procedure could be performed to optimize the radiation target
      geometry and to control the application of afterloading needles. In a prospective
      study, this new method was evaluated, with special regard for complications and
      tumor recurrence. METHODS: Anal cancer was restaged endosonographically six weeks
      after external beam radiation with 45 Gy. A computer-generated three-dimensional
      reconstruction of the tumor and radiation target simulation was performed based
      on endoanal sonographic imaging. By using a new type of applicator, which is
      permeable to ultrasound waves, the transperineal implantation procedure of
      afterloading needles could be controlled. Application needles were inserted into
      the target area according to the endoanal sonography-based dosimetry planing. The
      dose of the (high-dose rate) brachytherapy boost was started with two 6-Gy
      fractions, each within eight days. The fraction dose was reduced to 4 Gy to
      minimize side effects. Lymph node-positive tumors got additional chemotherapy (5
      fluorouracil and mitomycin C). RESULTS: From January 1992 until August 1996, we
      performed 42 endosonography-guided afterloading procedures in 18 patients. One
      patient underwent percutaneous radiation two years before and was treated only by
      afterloading radiation. In every patient, we found complete tumor remission at
      the end of radiotherapy. Three patients with a high-dose rate of 2 x 6 Gy
      developed radiogenic proctitis, and two patients developed ulceration, which lead
      to reduction of the dose. After reduction to 4 Gy per fraction, no more side
      effects could be seen. In follow-up (median, 24 (range, 1-56) months), we
      detected two anal cancer recurrences (2/18 patients). CONCLUSION: The radiation
      target field can be optimized by individual endosonography-based three
      dimensional tumor reconstruction and radiotherapy simulation. Endosonography
      guided transperineal implantation of afterloading needles can be performed
      according to the computer-generated simulation by using a new type of applicator.
      We could achieve total primary tumor remission in every patient. After reduction
      of the afterloading dose to 2 x 4 Gy, no brachytherapy-related side effects could
      be seen.

PMID- 9556241
TI  - Healing after anal fistulotomy: comparative study between HIV+ and HIV- patients.
AB  - PURPOSE: The aim of this work was to compare wound-healing after anal fistulotomy
      in human immunodeficiency virus (HIV)+ and HIV- patients and to recognize healing
      parameters in HIV+ patients. METHODS: Sixty patients were treated with
      fistulotomy for intersphincteric anal fistula. For each patient, we evaluated
      white blood cell count values, T CD4 counts, Centers for Disease Control and
      Prevention classification, and healing duration. There were 31 HIV+ patients (7
      A2; 1 A3; 7 C1; 6 C2; 10 C3). RESULTS: Seven C3 patients had incomplete healing.
      Statistically, there was no difference in the healing duration in HIV+ A2, C1,
      C2, and HIV-negative patients. C3 patients who did heal took longer than other
      HIV+ patients. T CD4 counts were similar to healed and not healed C3 patients,
      although healed C3 values of white blood cell counts were higher than not healed
      C3 values (4,450 and 2,380/mm3). CONCLUSION: After anal fistulotomy, HIV+ C3
      patients either had retarded healing or no healing at all. Therefore, we feel
      that surgery should be done only in emergency cases of anorectal diseases or in
      patients with more than 3,000 white blood cells/mm3.

PMID- 9556242
TI  - Handsewn vs. stapled anastomoses in colon and rectal surgery: a meta-analysis.
AB  - PURPOSE: Trials comparing handsewn with stapled anastomoses in colon and rectal
      surgery have not found statistical differences. Despite this, authors have
      differed in their conclusions as to which technique is superior. To help
      determine whether differences in patient outcomes are present, a meta-analysis of
      all trials was performed. METHOD: A meta-analysis of all randomized, controlled
      trials assessing handsewn and stapled colon and rectal anastomoses was done using
      a fixed-effects model. Outcome variables were mortality, technical problems, leak
      rates, wound infections, strictures, and cancer recurrence. Outcomes were
      assessed for all anastomoses involving the colon and for the subset of colorectal
      anastomoses. RESULTS: Thirteen distinct trials met the inclusion criteria.
      Intraoperative technical problems were more likely to occur with stapled than
      with handsewn anastomoses for all anastomoses (P < 0.0001) and for colorectal
      anastomoses (P < 0.001). Strictures were also more common following stapled
      anastomoses (P = 0.015 for all anastomoses; P = 0.028 for colorectal
      anastomoses). All other outcome measures, including mortality, clinical and
      radiologic leak rates, and local cancer recurrence rates showed no difference
      between groups. CONCLUSION: Although intraoperative technical problems and
      postoperative strictures were more common with stapled anastomoses, other outcome
      measures showed no difference between groups. Thus, both techniques are
      effective, and the choice may be based on personal preference.

PMID- 9556243
TI  - Defunctioning of the anorectum: historical controlled study of laparoscopic vs.
      open procedures.
AB  - BACKGROUND: Creating a defunctioning stoma for anorectal disease in patients in
      whom no resection or anastomosis is required appears eminently suited for
      laparoscopic techniques, with the intended advantages of early recovery, reduced
      pain, and avoidance of a laparotomy. OBJECTIVES: The study contained herein was
      undertaken to determine the feasibility of laparoscopic defunctioning stoma
      formation using a three-port technique (including one at the stoma site) and to
      compare initial results with a historical control group. METHODS: Duration of
      operation (anesthetic plus surgery), the time to tolerance of a liquid and then a
      solid diet, time to passage of flatus and feces, patient morphine requirements in
      the first 48 hours, and day of discharge were documented. RESULTS: Nineteen
      laparoscopic stomas were attempted (3 converted to open) and 23 open stomas were
      formed in the control group. The laparoscopic stoma group had lower morphine
      requirements (mean, 47.7 vs. 89.9 mg; P < 0.01), an earlier tolerance of both
      liquid (mean, 2.1 vs. 3.7 days; P < 0.01) and solid diets (mean, 3.6 vs. 5.5
      days; P < 0.001), and an earlier time to passage of both flatus (mean, 2.2 vs.
      3.6 days; P < 0.001) and feces (mean, 3.7 vs. 5.6 days; P < 0.001). Operating
      time was longer for the laparoscopic group (mean, 176 vs. 104 minutes; P <
      0.001), whereas median time to discharge from hospital was shorter (median, 8 vs.
      11 days; P = 0.014). Postoperative 30-day morbidity occurred in 1 of 19
      laparoscopic group patients and 4 of 23 open group patients. CONCLUSIONS: In this
      select group of patients requiring defunctioning stoma only, laparoscopic surgery
      is feasible and safe and may have advantages over open procedures of less pain,
      earlier tolerance of diet, earlier return of bowel function, and a shorter median
      length of stay.

PMID- 9556244
TI  - Role of Mycobacterium paratuberculosis in Crohn's disease: a prospective,
      controlled study using polymerase chain reaction.
AB  - PURPOSE: Mycobacterium paratuberculosis has been proposed as a causative agent in
      patients with Crohn's disease. The purpose of this study was to determine whether
      M. paratuberculosis was present in tissue from patients with Crohn's disease in a
      defined geographic area. METHODS: We prospectively evaluated, using polymerase
      chain reaction and culture, whether M. paratuberculosis was present in 44
      specimens (37 from intestinal mucosal biopsies and 7 from surgical resections)
      from patients with Crohn's disease, ulcerative colitis, or normal colonic mucosa.
      RESULTS: Of the 25 specimens tested from the 21 Crohn's patients, only 1 positive
      specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis
      patients and the 11 specimens from the 11 control patients failed to demonstrate
      a positive result with polymerase chain reaction. Cultures of all specimens
      revealed no growth of M. paratuberculosis. CONCLUSION: M. paratuberculosis was
      only rarely detected in biopsy or surgical specimens from patients with Crohn's
      disease. These results do not support a common causative role of M.
      paratuberculosis in Crohn's disease.

PMID- 9556245
TI  - Parameters of the rectoanal inhibitory reflex in patients with idiopathic fecal
      incontinence and chronic constipation.
AB  - PURPOSE: The rectoanal inhibitory reflex is a response of the internal anal
      sphincter to rectal distention, reflecting the functional nature of the anal
      sampling mechanism of rectal discrimination. The aim of this study was to assess
      the parameters of the rectoanal inhibitory reflex in healthy volunteers and
      incontinent and symptomatically constipated patients. METHODS: The rectoanal
      inhibitory reflex was recorded in 42 patients using reproducible threshold
      volumes. Excitatory and inhibitory latencies, maximum excitatory and inhibitory
      pressures, amplitude, and slope of inhibition, slope and time of pressure
      recovery, and area under the inhibitory curve were estimated. Pudendal nerve
      terminal motor latency and endoanal magnetic resonance imaging were performed in
      all incontinent patients. RESULTS: Significant linear trends were found for most
      parameters at each sphincter level when analyzed. Recovery time and area under
      the inhibitory curve differed between the sphincter levels and patient groups,
      with the most rapid recovery occurring in the distal sphincter of incontinent
      patients (P < 0.001). These pressure findings were not accounted for by
      differences in excitation between patient groups. CONCLUSION: A coordinated
      response by the internal anal sphincter to rectal distention with recovery of
      anal pressure from the distal to the proximal sphincter is suggested. Continence
      may rely on the character of internal anal sphincter inhibition, and recovery and
      preoperative assessment of rectoanal inhibitory reflex parameters may be
      important for predicting functional result following low anastomosis.

PMID- 9556246
TI  - Clinical outcome of anterior overlapping external anal sphincter repair with
      internal anal sphincter imbrication.
AB  - Fecal incontinence caused by overt anterior sphincter defects sustained during
      childbirth is usually treated by a delayed overlapping repair of the external
      anal sphincter. However, an obstetric trauma is frequently associated with
      disruption of the perineal body and loss of the distal rectovaginal septum. Data
      regarding a combined repair, consisting of restoration of the rectovaginal septum
      and perineal body, overlapping external anal sphincter repair, and imbrication of
      the internal anal sphincter, are scanty. PURPOSE: This prospective study was
      aimed at the following: 1) evaluating the clinical outcome of such an anterior
      anal repair in patients with fecal incontinence caused by obstetric trauma; 2)
      comparing the functional results with those obtained in a historical group of
      patients who underwent a conventional direct sphincter repair. METHODS: During
      the period between 1973 and 1989, 24 female patients (median age, 44 (range, 28
      67) years) with fecal incontinence underwent direct sphincter repair (Group I).
      During the period between 1989 and 1994, a consecutive series of 31 female
      patients (median age, 46 (range, 23-78) years) with fecal incontinence underwent
      anterior anal repair (Group II). RESULTS: At two years of follow-up, continence
      had been restored in 15 patients (63 percent) in Group I, whereas restoration of
      continence was successful in 21 patients (68 percent) in Group II. CONCLUSION:
      The more complex anterior anal repair fails to confer clinical benefit compared
      with the rather simple direct sphincter repair.

PMID- 9556247
TI  - Clinical outcome and bowel function following total abdominal colectomy and
      ileorectal anastomosis in the Oriental population.
AB  - Total abdominal colectomy with ileorectal anastomosis is a commonly performed
      surgical procedure. The postoperative outcome of these patients, however, has not
      been studied in detail in the Asian population. AIM: The purpose of this study
      was to analyze the functional outcome of patients following total abdominal
      colectomy and ileorectal anastomosis. METHOD: All patients subjected to a total
      abdominal colectomy with ileorectal anastomosis during a six-year period from
      February 1989 to October 1995 were reviewed. RESULTS: Sixty-six patients
      (male:female, 40:26) with a mean age of 55.2 (range, 20-88) years underwent total
      abdominal colectomy with ileorectal anastomosis. Median follow-up after surgery
      was 26 (range, 4-78) months. Indications for surgery were synchronous or
      metachronous tumors (18), complicated pancolonic diverticular disease (15),
      obstructed tumors with impending perforation (13), familial adenomatous polyposis
      (7), slow-transit constipation (6), and others (7). Mean operative time was 137
      +/- 48 minutes. Mean postoperative hospitalization was 13.3 +/- 11.9 days. Time
      to first bowel movement and commencement of solid diet were 4.7 +/- 1.8 and 7.2
      +/- 2.4 days, respectively. Four patients had prolonged postoperative ileus.
      Average stool frequencies per day were 5.5 at one week, 4.3 at one month, 3.9 at
      six months, 3.2 at one year, and 2.9 at two years postoperatively. Thirty-three
      patients (50 percent) required antidiarrheal treatment for a transient period,
      but none required long-term therapy. Ninety-seven percent of all patients rated
      the functional outcome as good to excellent, and 3 percent said it was fair.
      There was two perioperative mortalities. Five cases required re-laparotomy, three
      for anastomotic complications and two for hemoperitoneum. Five patients had
      recurrent admissions for adhesion colic, which resolved with nonsurgical therapy.
      Ten patients succumbed on follow-up, six to tumor recurrence, two to unrelated
      cancers (stomach and bladder), and three to medical conditions. CONCLUSION: The
      functional outcome of ileorectal anastomosis is generally rated as good to
      excellent by patients. Acceptable bowel function and control is regained within
      six months of the operation and levels off at one year after surgery, and no
      patient requires long-term antidiarrheal medication.

PMID- 9556249
TI  - Epidemiologic panorama of colorectal cancer in Mexico, 1980-1993.
AB  - INTRODUCTION: Colorectal cancer is the third cause of cancer-related death in the
      world, with 468,000 estimated deaths in 1993. In some countries mortality rates
      have started to decline, and survival rates have increased. In this study
      performed in Mexico, information is presented on the increase in mortality from
      this form of cancer, especially in more economically developed areas. METHODS:
      The mortality trend for colorectal cancer was evaluated and standardized by five
      year age groups in the period 1980 to 1993. Also, the standardized mortality
      ratio was calculated for Mexico's 32 states, as was the possible association
      between mortality and indicators of rurality level and fertility rates in the
      different regions of Mexico. RESULTS: In the period studied, 18,962 deaths were
      officially reported. The average age of death was 66 years. The mortality rate
      among women (1.8) was significantly higher than among men (1.55 per 100,000
      inhabitants). Mortality from colorectal cancer grew by 100 percent in both
      genders (beta = 0.089; P < 0.001), especially in the age group 34 and younger, in
      the 45 to 49 age group, and in the older than 75 age group (P < 0.05). The
      standardized mortality ratio was greater in the states in the north of Mexico.
      Finally, an inverse correlation was observed throughout Mexico between the
      rurality index (r = -0.60; P < 0.001) and the fertility rates (r = -0.43; P <
      0.05) and mortality from colorectal cancer. CONCLUSIONS: In this study, there is
      evidence that mortality from this cancer is higher in geographic areas with
      greater socioeconomic development, similar to regional patterns observed in other
      countries. In Mexico, the coming years will see a serious epidemic in mortality
      from this disease; therefore, immediate attention must be given to identifying
      the profile of high-risk subjects and implementing early cancer detection
      measures.

PMID- 9556248
TI  - Increased serum levels of transforming growth factor-alpha in patients with
      colorectal cancer.
AB  - PURPOSE: This study was conducted to investigate the serum levels of transforming
      growth factor-alpha in patients with colorectal cancer and to investigate the
      clinical significance of these levels in association with tumor stage and
      histologic differentiation. Also, serum levels of transforming growth factor
      alpha were measured after curative surgical resection. METHODS: Serum levels of
      transforming growth factor-alpha were measured in 42 consecutive patients with
      colorectal cancer before surgery, in 21 patients after surgical resection (part
      of the 42 preoperative patients), and in 20 healthy volunteers. We used TGF-alpha
      Assay. RESULTS: Serum levels of transforming growth factor-alpha in patients with
      colorectal cancer were significantly higher than in the healthy control group (P
      = 0.001). Significant elevations in serum levels of transforming growth factor
      alpha were found in 50 percent (21/42) of patients with colorectal cancer when
      the mean + 2 standard deviations (80.4 pg/ml) of the control group were used as
      the upper limit of the normal range. Serum levels of transforming growth factor
      alpha tended to decrease with increasing tumor size (n = 31; r = -0.52; P =
      0.002). Serum levels of transforming growth factor-alpha before surgery (89.7 +/-
      44.4 pg/ml; n = 21) significantly decreased to 60.3 +/- 19.8 pg/ml after surgical
      resections of tumors (P = 0.017). Serum levels of transforming growth factor
      alpha completely decreased to the same serum levels of the control group after
      surgical resections in all patients who had serum levels of transforming growth
      factor-alpha greater than mean + 2 standard deviations (80.4 pg/ml) of the
      control group preoperatively (n = 11; P = 0.002). CONCLUSIONS: Levels of
      preoperative transforming growth factor-alpha in patients with colorectal cancer
      appeared to be higher than levels measured in control subjects. Serum levels of
      transforming growth factor-alpha before surgery significantly decreased after
      surgical resections of tumors. Additional studies are warranted to determine if
      serum levels of transforming growth factor-alpha may be useful as a potential
      biomarker in the management of patients with colorectal cancer.

PMID- 9556250
TI  - Diagnostic and therapeutic applications of monoclonal antibodies in colorectal
      cancer.
AB  - PURPOSE: The study contained herein was undertaken to review and summarize the
      current literature on diagnostic and therapeutic applications of monoclonal
      antibodies in colorectal cancer. RESULTS: Limitations of traditional imaging
      techniques have encouraged development of targeted imaging strategies using
      radiolabeled monoclonal antibodies. Diagnostic immunoscintigraphy can detect
      lesions not identified by conventional imaging modalities, although it has not
      proven useful in the management of primary colorectal cancers and in hepatic
      metastases. Immunoscintigraphy shows promise in cases of local recurrence and
      rising carcinoembryonic antigen values; however, the impact of immunoscintigraphy
      on clinical outcomes and cost-effectiveness remains unproven. Radioimmunoguided
      surgery has been advocated as a method of more accurately detecting tumor
      extension and accomplishing radical resection. The technique remains
      controversial, and its use is not widespread. With respect to therapeutic
      applications, immunotherapy has most often been investigated in the setting of
      advanced stage disease. Results in this setting have been poor. In contrast,
      adjuvant immunotherapy after resection of Dukes C carcinoma has achieved
      convincing results, with improvements in survival comparable with that of
      adjuvant chemotherapy. Adjuvant trials are now under way to examine the
      effectiveness of monoclonal antibodies in the postoperative treatment of early
      stage (II) tumors and the combination of monoclonal antibodies and chemotherapy
      in advanced-stage (III) tumors. Bispecific antibodies, or immunoconjugates with
      cytokines or toxins, represent additional areas of interest and future
      investigations. CONCLUSIONS: At present, immunoscintigraphy is not sufficient to
      determine, by itself, resectability of colorectal tumor and has limited
      usefulness in select cases of recurrent cancer and possibly in cases of rising
      carcinoembryonic antigen values. Immunotherapy with monoclonal antibodies as a
      postoperative adjuvant treatment shows promise and is currently being
      investigated in national trials.

PMID- 9556251
TI  - Length measuring device for transrectal ultrasonography of anorectal lesions.
AB  - We, herein, describe an attachable measuring device for transrectal
      ultrasonography. It is a useful piece of equipment for measuring the precise
      length of a lesion and for fixing the position of the transducer under
      examination for sphincteric dynamics.

PMID- 9556252
TI  - Sacral insufficiency fractures--rare complication of pelvic radiation for rectal
      carcinoma: report of a case.
AB  - PURPOSE: The report contained herein presents a patient who developed severe back
      pain because of bilateral sacral insufficiency fractures after pelvic radiation
      for rectal carcinoma. METHODS: This is a case report and review of the literature
      for a rare complication of pelvic radiation. RESULT: The patient was diagnosed by
      computerized tomography and radionuclide bone scans. Bed rest and analgesia
      followed by rehabilitation provided good relief of the symptoms. CONCLUSION: A
      rare complication of pelvic radiation is insufficiency fractures of the pelvis.
      Early detection is important, because significant morbidity may result from
      delaying treatment. Unawareness of this complication may lead to diagnostic
      difficulties and unnecessary work-up.

PMID- 9556253
TI  - Involuntary contractions of the striated anal sphincters as a cause of
      constipation: report of a case.
AB  - PATIENT HISTORY: We present a case of anismus in a 36-year-old patient. He
      complained of therapy refractory constipation that had been present for 15 years,
      with delayed micturition and voiding by stages. METHODS AND RESULTS: During
      digital examination of the anal canal, we found spontaneous contractions of the
      sphincters at rest. The urethral pressure profile showed irregular contractions
      during micturition. The electromyogram, which was performed with concentric
      needle electrodes from the external anal sphincter, puborectalis, and external
      vesical sphincter, revealed synchronous contractions of these muscles. Injections
      of botulinum toxin into the sphincters showed good effects and no incontinence.
      CONCLUSION: Focal dystonia of the striated anal and vesical sphincters is a very
      rare cause of constipation but should be included in the differential diagnosis.

PMID- 9556254
TI  - Self-assessment quiz. Chronic idiopathic rectal pain: risk factor for
      postoperative complications in colorectal surgery: local excision of rectal
      cancer should be done.

PMID- 9556255
TI  - Are we there yet?

PMID- 9556256
TI  - Save the trapezium: double interposition arthroplasty for the treatment of stage
      IV disease of the basal joint.
AB  - Twenty patients with symptomatic stage IV basal joint (pantrapezial) arthritis
      were treated with double interposition arthroplasty, a new technique that
      resurfaces the degenerative trapeziometacarpal and scaphotrapezial joints after
      minimal distal trapezial resection. The results of the 21 procedures were
      reviewed clinically and radiographically after a mean follow-up period of 34
      months (minimum, 1 year). Ninety-one percent of the patients were completely
      satisfied. Seventy-one percent were entirely free of pain, and an additional 24%
      noted only occasional, mild, high-stress pain that did not limit their
      activities. One case was a clinical failure. Objectively, all 21 basal joints
      were stable, with active range of motion to within 90% of normal. Mean grip
      strength increased 32%, from a force of 26.1 kg to 33.9 kg (p < .01). Key pinch
      strength increased from a force of 5.3 kg to 6.0 kg (an 11% increase; p = .05). A
      new method of determining changes in basal joint height indicated a mean decrease
      in height of 5.3% (range, 0%-12%) at rest and 8.1% (range, 0%-20%) under axial
      compression. This difference was statistically but not functionally significant.
      Overall, there were 95% good or excellent results and 1 poor result. We believe
      this technique is simple and preserves the osseous foundation of the basal
      joints. These results compare favorably with arthroplasties that include
      trapezium excision for the treatment of stage IV basal joint arthritis.

PMID- 9556257
TI  - Scapholunate ligament reconstruction using a bone-retinaculum-bone autograft.
AB  - This study was designed to evaluate the use of a locally available bone
      retinaculum-bone graft in the reconstruction of the completely torn scapholunate
      (SL) ligament. Nineteen consecutive patients (14 with dynamic instability and 5
      with static instability) underwent SL ligament reconstruction using an autogenous
      bone-retinaculum-bone graft taken from the third dorsal compartment region. All
      patients underwent arthroscopy to document a torn SL ligament. The bone plugs on
      the graft were fitted into the dorsal scaphoid and lunate, respectively, with the
      retinaculum periosteal soft tissue intervening sleeve arching between these 2
      bones. The SL interval was reduced and pinned for 8 weeks with cast
      immobilization. The follow-up period averaged 3.6 years (minimum, 24 months). Of
      the 14 patients with dynamic instability, 12 had no pain and 2 had pain with
      heavy activity of the wrist. Range of motion (ROM) decreased slightly from
      preoperative values, and grip strength improved 46%. Thirteen patients were
      completely satisfied and returned to their former work activities, and 1 returned
      to modified work activities. Of the 5 patients with static instability, 2 had no
      pain after surgery, 1 had pain with heavy activity, and 2 had constant pain. ROM
      in this group decreased moderately in extension/flexion from the preoperative
      values. Grip strength improved 30% from preoperative values. Satisfaction was
      rated as complete by 1 patient and partial by 2 patients; 2 patients were
      dissatisfied. Two patients returned to their former jobs, 2 returned to modified
      duties, and 1 is on disability. Reconstruction of the SL ligament using a bone
      retinaculum-bone autograft is predictable in patients with dynamic instability.
      Use of this technique with static SL instability is questionable; these patients
      may require a stronger construct to prevent recurrence of the SL gap.

PMID- 9556258
TI  - Scapholunate ligament reconstruction using a bone-retinaculum-bone autograft: a
      biomechanic and histologic study.
AB  - A new surgical technique has been recently described that involves reconstruction
      of the dorsal aspect of the scapholunate ligament (DSLL) with a bone-retinaculum
      bone (BRB) autograft preparation from Lister's tubercle. In this study, the
      mechanic and histologic properties of the 2 tissues were compared. The BRB and
      DSLL specimens were harvested from 6 fresh-frozen human cadaveric forearms. The
      specimens were measured and then tested in tension with an MTS 810 servohydraulic
      materials testing machine at a rate of 10 mm/min. The BRB autograft was
      significantly weaker than the DSLL. However, because the mean cross-sectional
      area of the DSLL was more than 3 times as large as that of the BRB autograft, the
      failure stress (failure force/cross-sectional area) of the BRB autograft was not
      significantly different from that of the DSLL. Histologically, the DSLL and BRB
      autograft were also similar. These findings suggest that the BRB autograft may be
      appropriate graft material for scapholunate ligament reconstruction, but that
      structural parity with DSLL will ultimately depend on remodeling and hypertrophy
      during healing. This also highlights the importance of using a large BRB
      autograft to approximate the strength of the DSLL as much as possible, and that
      the BRB autograft must be protected postoperatively as it heals and remodels.

PMID- 9556259
TI  - Wide excision of the distal ulna: a multicenter case study.
AB  - Excision of the distal ulna to treat degenerative disease or instability has
      fallen into disfavor following reports of radioulnar impingement, carpal
      instability, and distal ulnar instability. Alternative procedures for
      reconstruction of the painful distal ulna have been developed to address these
      problems; the results have been generally favorable. When faced with distal ulnar
      reconstruction that has failed after multiple surgical procedures, or a distal
      ulnar neoplasm, the surgeon is left with few treatment options. Creation of a one
      bone forearm, free fibular transfer, and allograft replacement have been
      attempted, with mixed outcomes. We report the results of 5 men and 7 women who
      underwent wide excision of the distal ulna, defined as surgical excision of 25%
      to 50% of the ulnar length. The diagnosis was failed distal radioulnar
      reconstruction or excision in 8 patients, osteomyelitis in 1, congenital
      pseudoarthrosis of the radius in 1, and neoplasm in 2. No soft tissue
      reconstruction was performed. Patients were examined at an average of 22 months
      after surgery for radiocarpal and radioulnar instability, functional outcome,
      pain relief, grip strength, and range of motion. Nine of the 12 procedures
      resulted in good or excellent results; 1 patient had a fair result after
      resection for osteosarcoma, and the procedure in 2 patients failed, requiring
      conversion to a one-bone forearm. Grip strength was restored to 75% of the normal
      side and range of motion was restored to 86% of the normal side. Wide excision of
      the distal ulna without soft tissue reconstruction is a simple and durable
      treatment of neoplasms of the distal ulna or salvage of the failed reconstruction
      of the distal radioulnar joint. We do not recommend its use in patients with
      incompetency or disruption of the interosseous membrane.

PMID- 9556261
TI  - Intrasound vibration in the early diagnosis of scaphoid fracture.
AB  - A prospective trial was designed to assess the sensitivity and specificity of
      intrasound vibration for the early detection of scaphoid fracture. We replicated
      the method described by Finkenburg et al. (J Hand Surg 1993;18A:4-7) in an
      attempt to corroborate their results. We found the test to be 73% sensitive and
      51% specific. Because the test was not 100% sensitive, as claimed by Finkenburg
      et al., we discontinued the use of this device in our hospital.

PMID- 9556260
TI  - Is intrasound vibration useful in the diagnosis of occult scaphoid fractures?
AB  - This study was designed to confirm the results of Finkenberg et al. (J Hand Surg
      1993;18A: 4-7), who found a high sensitivity (100%) and specificity (95%) of the
      intrasound vibration method in diagnosing occult scaphoid fractures. These occult
      scaphoid fractures are not visible on x-ray films, but clinically the patients
      are suspected of having a scaphoid fracture. A vibratory apparatus is placed over
      the anatomical snuff-box and a vibration of 100 mW is emitted; a painful
      sensation is produced if the scaphoid is fractured. Thirty-seven consecutive
      patients with a clinically suspected scaphoid fracture were evaluated. In 6
      patients, a scaphoid fracture was radiographically identified; in the remaining
      31 patients, a 3-phase bone scan was obtained. Eleven wrists showed increased
      uptake over the scaphoid and were considered to have an occult scaphoid fracture.
      In this group, bone scintigraphy was used as the reference standard. The
      vibration test was painful in 1 of 6 patients with a proven scaphoid fracture and
      in 3 of the 11 patients with a positive bone scan. In contrast to the results of
      Finkenberg et al, the intrasound vibration method shows a sensitivity of 24%, a
      specificity of 85%, a positive predictive value of 40%, and a negative predictive
      value of 65%. We conclude that the accuracy of intrasound vibration is low and
      that it is not useful in the diagnosis of scaphoid fractures.

PMID- 9556262
TI  - Surgical treatment of carpal tunnel syndrome and trigger digits in children with
      mucopolysaccharide storage disorders.
AB  - The role of surgical intervention for carpal tunnel syndrome (CTS) and trigger
      digits in children with mucopolysaccharide storage disorders (MPSDs) has not been
      clearly defined, particularly as the treatment of the underlying disease has
      advanced to include bone marrow transplantation. This study reviews our
      experience in the treatment of CTS and trigger digits in 22 children with MPSDs
      who were evaluated for CTS by electromyographic (EMG)/nerve conduction velocity
      (NCV) testing. Seventeen children were diagnosed with CTS by EMG/NCV testing and
      were treated with bilateral open surgical release with or without flexor
      tenosynovectomy. The EMG/NCV testing revealed normal results in 5 patients who
      are subsequently being monitored. Forty-five digits in 8 children were diagnosed
      clinically with trigger digits. Nineteen digits were treated by annular pulley
      release alone. Twenty-six digits were treated by annular pulley release with
      partial flexor digitorum superficialis tendon resection. The average age at the
      time of hand surgery was 6.3 years, and at the time of follow-up, 9.6 years.
      Postoperative EMG/NCV testing in 7 children showed 1 with improvement and 6 with
      normalization. None of the patients undergoing carpal tunnel release went on to
      develop thenar atrophy or absent sensibility, as has been reported in untreated
      cases. Patients were evaluated for triggering digits both by preoperative tendon
      palpation and by intraoperative flexor tendon excursion at the time of open
      carpal tunnel release. All patients undergoing trigger release had improved
      active digital flexion seen at the final follow-up visit. Because of the very
      high incidence of CTS and trigger digits in this population, the authors
      currently recommend routine screening of EMG/NCV for all children with MPSDs.
      Early surgical intervention for nerve compression and stenosing flexor
      tenosynovitis can maximize hand function in these children.

PMID- 9556263
TI  - The role of ulnar nerve transposition in ulnar nerve repair: a cadaver study.
AB  - Ulnar nerve transposition at the elbow is recommended to diminish nerve gaps
      during neurorrhaphy. We undertook a cadaver study to determine the gap distance
      that can be overcome by subcutaneous transposition at the elbow, evaluating
      lacerations 2.0 cm distal to the medial epicondyle and 2.0 cm proximal to the
      wrist crease. With a 100-g load on each nerve stump, gaps that could be overcome
      were measured before and after transposition in different elbow and wrist
      positions. For the distal forearm lacerations, wrist position significantly
      affected nerve gap, while transposition and elbow position did not. Nerve gap was
      significantly reduced by approximately 11 mm with wrist flexion from 0 degrees to
      45 degrees. For proximal forearm lacerations, gap distance was significantly
      affected by transposition and was dependent to a greater extent on the
      interaction between transposition and elbow position, with wrist position having
      no effect. A clinically relevant scenario for the proximal laceration compared
      the pretransposition gap with the elbow and wrist at neutral with the
      posttransposition gap with the elbow and wrist flexed. Posttransposition gap
      reduction, with elbow and wrist flexion at 45 degrees, was approximately 9 mm and
      was not significant. To span a gap near the elbow, we estimate that more than 45
      degrees of elbow flexion is required.

PMID- 9556264
TI  - Anatomy and internal topography of the musculocutaneous nerve: the nerves to the
      biceps and brachialis muscle.
AB  - One hundred twelve musculocutaneous nerves from 56 cadavers were examined to
      determine branching patterns of innervation and internal neurotopography. There
      were 3 distinct types of branching patterns for biceps innervation: in 62%, there
      was 1 branch only; in 33%, 2 branches; and in 5%, 3 branches. The origin of the
      first branch averaged 130 mm from the acromion regardless of branching type. The
      maximum distance between the first and second branch was 53 mm. In 92%, there was
      only 1 branch to the brachialis muscle. It always emerged from the main trunk
      distal to the nerve to the biceps and averaged 170 mm from the acromion. Internal
      topography was studied from 1-mm-thick serial sections of the musculocutaneous
      nerve in 5 fresh cadaver arms. The group of fasciculi of the nerve to the biceps,
      the nerve to the brachialis, and the lateral cutaneous nerve of the forearm were
      constantly located from lateral to medial. The fasciculi of the nerve to the
      biceps traveled proximally in the musculocutaneous nerve for an average distance
      of 63 mm.

PMID- 9556265
TI  - Microarterial anatomy of the lesser toe proximal interphalangeal joints.
AB  - Successful free tissue transfer requires detailed knowledge of the pertinent
      microvascular anatomy of the donor site. The lesser toe proximal interphalangeal
      joints are a source of vascularized autologous tissue. In 20 adult cadaver feet,
      the arterial anatomy of the second, third, and fourth toes was studied using
      colored latex and India ink injection. The second, third, and fourth dorsal
      metatarsal arteries produced small or absent dorsal digital arteries in 72.5% of
      distal dissections. The proper digital arteries were 0.93 to 1.37 cm in length.
      An additional 2.3 to 2.83 cm of length can be gained by use of the plantar
      metatarsal arteries if the dorsal metatarsal or dorsal digital arteries are
      inadequate. The diameter of the medial proper digital arteries (range, 1.2-1.26
      mm) was larger than the lateral proper digital arteries (range, 0.66-0.99 mm).
      The proper digital arteries of the lesser toes provide the predominant arterial
      supply of the proximal interphalangeal joints through a system of transverse and
      longitudinal arches.

PMID- 9556266
TI  - Two-, four-, and six-strand zone II flexor tendon repairs: an in situ
      biomechanical comparison using a cadaver model.
AB  - A dynamic in vitro model of zone II flexor tendon repair was used to compare
      gliding resistance, gap formation, and ultimate strength of the 2-, 4-, and 6
      strand repair techniques. Each of 12 hands was mounted to a loading frame with 3
      flexor tendons attached to individual pneumatic cylinders. A spring attached to a
      pin through the distal end of each digit provided a 1.25-kg resistance force. The
      force required to flex each proximal interphalangeal joint to 90 degrees was
      determined. Following this, the tendons were sectioned and each was repaired
      using a different technique so that each specimen acted as its own control. The 2
      and 4-strand core sutures were placed using a suture interlock technique with
      radial and ulnar grasping purchase of the tendon on each side of the transverse
      part of the repair. Each repair was accomplished using a single core stitch with
      the knot buried between the tendon ends. The 4-strand repair involved an
      additional horizontal mattress suture with the knot buried. Repair of the dorsal
      side of the tendon was performed followed by core suture placement. The palmar
      portion of the peripheral locking suture was completed after core suture
      placement. Following repair, each hand was remounted on the frame and cycled
      1,000 times. After cyclic loading, the resulting gap between the repaired ends of
      each tendon was measured, the tendons were removed from the hand, and each was
      loaded to failure in tension. All tendon repairs showed a small, but not
      statistically significant, increase in gliding resistance after reconstruction.
      The 2-strand repair had significantly greater gap formation after cyclic loading
      (mean gap, 2.75 mm) than either the 4-strand (0.30 mm) or 6-strand (0.31 mm)
      repair. The tensile strength of the 6-strand repair (mean, 78.7 N) was
      significantly greater than either the 4-strand (means, 43.0 N) or 2-strand (mean,
      33.9 N) repair.

PMID- 9556267
TI  - Differences in proliferative rate and collagen lattice contraction between
      endotenon and synovial fibroblasts.
AB  - Injured and surgically repaired tendons heal with the formation of scar tissue.
      Scar tissue represents 1 of the most unpredictable factors contributing to
      postoperative morbidity. The main cell involved in scar formation is the
      fibroblast. The relative activity of fibroblasts from the fibro-osseous sheath
      (the tissue surrounding the tendon in zone II) and the endotenon (the core of the
      tendon) with respect to proliferation and the ability to contract a collagen
      lattice were compared in vitro. The fibroblasts derived from the fibro-osseous
      sheath were more active in both these respects. In addition, the amount of matrix
      metalloproteinase activity was found to be greater for the fibro-osseous sheath
      fibroblasts, implying a greater capacity to degrade and disorganize connective
      tissue and thus migrate. These results imply that the fibro-osseous fibroblasts
      represent a more active population of cells compared with endotenon fibroblasts,
      and perhaps should be specifically targeted in future modes of therapy.

PMID- 9556268
TI  - Excursion properties of tendon graft sources: interaction between tendon and A2
      pulley.
AB  - We measured excursion resistance of 4 different tendons (flexor digitorum
      superficialis, the portion of the extensor indicis proprius tendon beneath the
      extensor retinaculum, the portion of the extensor indicis proprius tendon distal
      to the extensor retinaculum, and palmaris longus) beneath the A2 pulley.
      Intrasynovial tendons (i.e., flexor digitorum superficialis and the portion of
      the extensor indicis proprius beneath the extensor retinaculum) produced less
      excursion resistance than extrasynovial tendons (i.e., the portion of the
      extensor indicis proprius distal to the extensor retinaculum and palmaris
      longus). The excursion resistance of the intrasynovial portion of the extensor
      indicis proprius tendon was significantly lower than that of the extrasynovial
      portion of the same tendon. Intrasynovial tendons may be preferred to
      extrasynovial tendons when choosing a tendon graft source and graft gliding under
      a pulley is a consideration.

PMID- 9556269
TI  - Flexor tendon-pulley interaction after annular pulley reconstruction: a
      biomechanical study in a dog model in vivo.
AB  - The excursion resistance between the canine flexor digitorum profundus tendon and
      A2 pulley was compared after pulley reconstruction using tendon grafts of either
      intrasynovial or extrasynovial origin at 10 days, 3 weeks, and 6 weeks after
      surgery. The changes over time in the underlying flexor digitorum profundus
      tendon after pulley reconstruction were also evaluated. The excursion resistance
      for both types of pulley reconstruction was significantly greater than that of
      the control group at all time periods. The excursion resistance of the
      extrasynovial tendon graft reconstruction was greater than that of intrasynovial
      pulley reconstruction at all time periods. In conclusion, pulley reconstruction
      with intrasynovial tendon grafts may facilitate tendon gliding after surgery.

PMID- 9556270
TI  - The effects of proximal load on the excursion of autogenous flexor tendon grafts.
AB  - To determine the relationship between the intrinsic properties of tendon and
      tendon excursion in 2 types of autogenous tendon grafts, hindpaw intrasynovial
      and extrasynovial tendons were transferred to the lateral and medial forepaws of
      adult mongrel dogs (16 experimental and 16 control tendons). After each digit was
      marked with radiopaque markers, it was placed in a specialized jig, and weights
      of 25 g, 100 g, or 200 g were applied to the flexor tendons. Specialized
      radiographs were obtained with the digit in flexion and extension. Tendon
      excursion and joint rotation were calculated. There were no statistically
      significant differences between experimental groups for tendon excursion or for
      joint angular rotation (p > .05). For intrasynovial tendon grafts, the angular
      rotation per millimeter tendon excursion was 10.9 degrees +/- 2.4 degrees/mm, 9.4
      degrees +/- 1.2 degrees/mm, and 9.0 degrees +/- 1.4 degrees/mm with 25-g, 100-g,
      and 200-g loads, respectively. Comparisons between experimental groups revealed
      that a statistically significant difference could not be determined (p > .05).
      With varying proximal loads, both intrasynovial and extrasynovial grafts showed
      similar amounts of tendon excursion. Variations in proximal load did not
      significantly influence the amount of excursion within the range of loads tested.
      Based on these data, it appears that the difference in repair potential for these
      2 types of tendon grafts is not related to a differential in the amount of tendon
      graft excursion following transfer to the synovial space.

PMID- 9556271
TI  - Staged opposition transfer.
AB  - Six patients sustained extensive hand and upper limb trauma, including median
      nerve and/or thenar muscle loss. Initial treatment consisted of various median
      nerve and/or soft tissue reconstructions. Because of extensive palmar scarring
      and lack of useful opposition (Kapandji stage 3), a 2-stage opposition transfer
      was performed. In stage 1, a silicone rod was placed along the path of the
      intended tendon transfer. In stage 2, the rod was removed and the donor tendon
      was passed through the pseudosheath to the point of insertion at the thumb. All
      patients were monitored for a minimum of 1 year and all achieved significant
      functional improvement, documented by Kapandji stage 6 opposition in 1 patient
      and by at least stage 7 or 8 opposition in the other 5 patients.

PMID- 9556272
TI  - Ulnar nerve compression following flexor digitorum superficialis tendon transfers
      around the ulnar border of the forearm to restore digital extension: case report.
AB  - This case report describes a complication that occurred following long and ring
      finger flexor digitorum superficialis tendon transfers routed around the ulnar
      border of the forearm to restore digital extension. An ulnar mononeuropathy
      developed in the early postoperative period that was characterized by decreased
      ring and small finger sensation and interosseous muscle weakness. Operative
      exploration demonstrated extrinsic compression of the ulnar nerve by the long and
      ring finger flexor digitorum superficialis tendons. When superficialis tendon
      transfers are chosen to restore digital extension, passage around the radial side
      of the forearm or through the interosseous space are recommended to avoid this
      potential complication.

PMID- 9556273
TI  - Open reduction and internal fixation of unstable distal radius fractures with a
      low-profile plate: a multicenter study of 73 fractures.
AB  - A study of acute, dorsally displaced, unstable (high-energy) fractures of the
      distal radius was conducted to determine the safety and efficacy of a new low
      profile plate for unstable distal radius fractures. Thirteen surgeons in 11 US
      cities participated in the study. A minimum follow-up period of 1 year was
      required to be included in the study. Seventy-three fractures in 71 patients met
      this criterion. Each fracture was treated according to a prospective protocol. An
      autogenous bone graft was used in 64 fractures. All procedures were completed
      using a radiolucent sterile traction table. No external fixators were used either
      during or after the operation. After bone grafting and while in traction, a
      fracture reduction clamp with a template preshaped to the normal contour of the
      dorsal radial metaphysis molded the fracture into reduction and then allowed
      precision drilling of the holes for the plate. Active wrist motion began at an
      average of 14 days. Satisfactory open reduction was obtained in 93% of the
      fractures and maintained in 88%. Ninety-five percent of the fractures
      demonstrated good or excellent outcomes using a standardized evaluation. Eighty
      one percent of the outcomes were rated as excellent. This initial report
      demonstrates that the method is a safe and effective treatment for acute,
      unstable, dorsally displaced fractures of the distal radius.

PMID- 9556274
TI  - Self-tapping versus standard tapped titanium screw fixation in the upper
      extremity.
AB  - Most screws used in fracture fixation necessitate a separate step for tapping of
      the screw hole. Titanium screw systems have been developed in which the screws
      can be inserted directly after a drill hole is made. These self-tapping screws
      thereby eliminate an operative step. A retrospective study was conducted that
      evaluated all wrist and hand procedures performed between January 1992 and
      December 1994 by 1 surgeon using screw fixation. The results of 39 cases treated
      with standard tapped titanium screws were compared with 28 cases treated with
      self-tapping titanium screws. Nearly identical union and complication rates were
      obtained in each group. Comparable results can be obtained with self-tapping
      screw fixation, which limits the number of instruments needed, eliminates an
      operative step, and thereby may diminish operative risk and shorten operative
      time.

PMID- 9556275
TI  - The prefabrication of a bone graft in a rat model.
AB  - The prefabrication of bone grafts in a rat model was investigated. In 26 Sprague
      Dawley rats, free iliac crest bone graft was harvested, bivalved, and reinserted
      heterotopically into the groin, where it was closed around the mobilized
      superficial inferior epigastric vascular bundle. In half the animals, the
      vascular bundle remained in continuity as a flow-through pedicle (group 1); in
      the remaining animals, the pedicle was ligated and divided distal to the bone
      graft. All grafts were isolated from other tissues by a silicone sheet envelope.
      At 3 or 6 weeks, the grafts were re-explored and analyzed by India ink perfusion
      and histologic examination for evidence of viability and neovascularization.
      Three weeks after insertion, India ink perfusion of the group 1 and 2 grafts
      revealed neovascularization extending to the periphery of the graft, and
      histologic examination showed extensive new bone formation on endosteal,
      periosteal, and trabecular surfaces of the graft. Six weeks after insertion,
      creeping substitution had almost completely remodelled the cortical and
      cancellous bone of both group 1 and 2 grafts to create a viable vascularized bone
      graft on a pedicle. In 3 control nonvascularized grafts (free iliac cortical bone
      without an implanted pedicle), all pre-existing bone of the graft was dead 3
      weeks after insertion, and only very limited new bone formation was present
      within the graft.

PMID- 9556276
TI  - Evaluation of "neocollateral" ligament formation by magnetic resonance imaging
      after total excision of the proximal interphalangeal collateral ligaments.
AB  - The presence of palpable thickening and maintenance of stability within weeks of
      total excision of the proximal interphalangeal (PIP) joint collateral ligaments
      is an established, although somewhat mysterious, phenomenon. To further
      investigate this postoperative thickening, magnetic resonance imaging (MRI) scans
      were obtained on 10 joints in 9 patients who had undergone total ligament
      excision for posttraumatic stiff PIP joints 3 months to 14 years earlier.
      Although the ultrastructure of these newly formed structures is yet unknown,
      their palpable consistency, MRI contour, distribution, and signal intensity
      suggest the formation of a new soft tissue structure, albeit scar, which has all
      the attributes of a collateral ligament. This MRI of a "neocollateral ligament"
      would help explain the consistent observation of complete joint stability within
      weeks following total excision of both PIP joint collateral ligaments. All
      patients from the 14-year span sampled were found to have a similar, consistent,
      linear low signal density structure crossing the joint margins and essentially
      identical to that of a normal collateral ligament.

PMID- 9556278
TI  - Pathologic fracture of the scaphoid due to enchondroma: treatment with
      vascularized bone grafting. report of a case.
AB  - Enchondroma of the scaphoid has been rarely reported. A young male manual worker
      presented with a pathologic fracture on the lesion. It was successfully managed
      with a vascularized bone graft from the dorsum of the distal radius.

PMID- 9556277
TI  - Fitting a hand-glove prosthesis to enhance the reconstructed mutilated hand.
AB  - Microsurgical reconstruction of the severely mutilated hand aimed at improving
      prehensile functions often does not address the esthetic aspects of the hand. The
      poor appearance of the reconstructed hand affects its active display and use. A
      hand-glove prosthesis may be prescribed in this instance to enhance the overall
      form and function of the mutilated hand. We reviewed 16 cases of mutilating hand
      injuries in which surgical reconstructions were performed and the patients were
      subsequently fitted with a hand-glove prosthesis to augment the outcome. An
      improved appearance was achieved in all patients fitted with the prosthesis. The
      patients' sense of confidence was also enhanced, which in turn promoted the
      active and open use of the reconstructed hands. While prescribed primarily to
      improve the appearance of the reconstructed hands, these prostheses were
      documented to enhance the physical hand functions in 11 cases by increasing the
      span of the hand and providing an opposable post and a palmar base for holding
      and for anchorage. The prosthesis enhanced assistive functions of the
      reconstructed hands and freed the contralateral normal hand for use in bimanual
      activities, such as holding a wallet and taking out money, supporting a note pad
      for writing, and holding a plate at buffet receptions. At the 18-month follow-up
      visit, 13 (87%) of the patients continued to use their prosthesis. Wear and tear
      were problems associated with the frequent use of the prosthesis. The expected
      life span of the prosthesis with daily use ranged from 2 to 3 years. All the
      patients acknowledged that the prosthesis played a role in their rehabilitation
      and that it helped them to overcome the initial psychological trauma and to come
      to terms with their physical loss.

PMID- 9556279
TI  - Enchondroma protuberans: a case report.
AB  - Enchondroma protuberans is a rare benign cartilaginous tumor. There have been
      only 5 cases previously described in the world literature. It must be
      differentiated from other more common and aggressive tumors to avoid radical
      resection. A case report of a 7-year-old boy presenting with enchondroma
      protuberans in the third metacarpal is presented. The patient underwent an
      initial incisional biopsy followed by a marginal resection of the soft tissue
      component and intramedullary curettage. After a 36-month follow-up period, there
      is no evidence of recurrence.

PMID- 9556280
TI  - Perineurioma of the finger: case report of a rare peripheral nerve sheath
      neoplasm of pure perineurial cell lineage.
AB  - A 1.9-cm extraneural soft tissue tumor located on the palmar aspect of the index
      finger of a 50-year-old woman was excised. Depicting many histopathologic
      patterns and a full range of cellularity, the tumor was exclusively composed of
      epithelial membrane antigen/vimentin-positive and S-100 protein/Leu-7-negative
      neoplastic cells of perineurial lineage. Soft tissue (extraneural) perineurioma,
      a rare variant of benign peripheral nerve sheath tumor, should be included in the
      differential diagnosis of tumor and tumor-like conditions affecting soft parts of
      the hand.

PMID- 9556281
TI  - Upper extremity infections in patients with the human immunodeficiency virus.
AB  - Twenty-eight patients with upper extremity infections and positive for the human
      immunodeficiency virus (HIV) were identified. The risk factor for HIV infection
      was intravenous drug injection in 24 patients, homosexual contact in 3, and
      heterosexual contact in 1. Eight of the patients had the acquired
      immunodeficiency syndrome. Two of the cases were prolonged herpetic infections of
      more than 6 months' duration that did not respond to oral acyclovir. The other 26
      cases were bacterial in origin. Twenty-six of 28 cases responded to therapy with
      resolution of the infection. One patient refused surgical treatment and one died
      of systemic illness before resolution of the hand infection.

PMID- 9556282
TI  - Prospective multi-center trial of a plate for dorsal fixation of distal radius
      fractures.

PMID- 9556283
TI  - Relation of preoperative nerve-conduction values to outcome in workers with
      surgically treated carpal tunnel syndrome.

PMID- 9556284
TI  - Percutaneous drainage of thoracic collections.
AB  - Various infected and noninfected thoracic fluid collections may be diagnosed and
      treated by interventional radiologic techniques. The core procedure of ultrasound
      guided thoracentesis has been expanded to allow catheter drainage of empyema,
      bronchopleural fistula, abscesses in the lung, mediastinum, pericardium, and
      infected tumors. Tailored use of guidance methods permits effective evacuation of
      most of these abscesses and noninfected collections. This paper details the
      authors' approach to each of these entities while highlighting the results and
      expected pitfalls of these techniques.

PMID- 9556285
TI  - Percutaneous drainage of pleural collections.
AB  - Pneumothorax is a frequent complication of interventional pulmonary procedures.
      Percutaneous catheter placement enables safe and effective drainage of
      pneumothoraces with rapid restoration of vital capacity, oxygenation, and lung
      reexpansion.

PMID- 9556286
TI  - Arterial embolization in the chest.
AB  - Transcatheter therapy is an effective technique in the treatment of vascular
      abnormalities in the chest. Pulmonary arteriovenous malformations, associated
      with the clinical sequellae of dyspnea, stroke, brain abscess, and hemoptysis,
      can be treated by transcatheter embolization with metallic coils or occlusion
      balloons. The results of treatment are excellent, with improvement seen in
      symptoms and physiologic parameters. The bronchial arteries and systemic
      nonbronchial collateral arteries supplying the tracheobronchial tree are most
      frequently involved in massive hemoptysis, a serious disorder with associated
      high rates of morbidity and mortality. Transcatheter embolization of these
      arteries is both safe and effective, requiring a thorough understanding of the
      arterial anatomy and technique of embolization.

PMID- 9556288
TI  - Pictorial essay: thoracic cardiovascular complications of acquired
      immunodeficiency syndrome.
AB  - Patients with acquired immunodeficiency syndrome frequently develop complications
      of cardiac, pericardial, and thoracic vascular origin. The purpose of this
      pictorial essay is to review the most common etiologic and diagnostic imaging
      findings of these diseases. Patients with acquired immunodeficiency syndrome
      often demonstrate enlargement of the cardiac silhouette on the chest radiograph.
      While the cause of this finding may be clinically evident, the authors share
      cases in which chest computed tomography, echocardiography, and nuclear medicine
      studies better reveal the nature of underlying cardiac and pericardial
      abnormalities. Thoracic vascular complications, including pulmonary hypertension,
      pulmonary thromboembolism, and the sequelae of indwelling venous catheters, are
      also addressed.

PMID- 9556289
TI  - Segmental pulmonary arteries: two-dimensional and three-dimensional time-of
      flight magnetic resonance angiography.
AB  - The authors compared two-dimensional (2D) and three-dimensional (3D) time-of
      flight (TOF) magnetic resonance angiography in ten healthy volunteers to
      establish which of two techniques is more effective in representing the pulmonary
      segmental arteries. No respiratory trigger or electrocardiogram gating was used.
      Presaturation pulses were used to eliminate venous flow. Images acquired in the
      sagittal planes were processed using maximum intensity projection. A total of 200
      segmental arteries were evaluated with each technique by three observers (M.S.,
      C.S., A.R.) in terms of vessel visibility. There was no significant difference
      among the observers' interpretations (p > 0.05). On average, 2D fast, low-angle
      shot breath-hold TOF sequences showed 136.1 of 200 (68%) segmental arteries, 74.1
      of 100 in the right lung and 62 of 100 in the left lung. Three-dimensional fast
      imaging with steady state precession showed 171.6 of 200 (85.8%) segmental
      arteries, 94 of 100 in the left lung and 77.6 of 100 in the left lung. Three
      dimensional imaging appeared to be better than 2D MRA for demonstration of
      segmental pulmonary arteries.

PMID- 9556287
TI  - Expandable metallic stents in benign tracheobronchial obstruction.
AB  - Expandable metallic stents offer advantages over previously available techniques
      for treating benign tracheobronchial stenosis or obstruction. Endoluminal stent
      placement offers a rapid and effective means of opening up narrowed airways, and
      results in excellent relief of symptoms and improvement in pulmonary function.
      Because they are delivered in a nonexpanded state using flexible over-wire
      systems, they can be placed using a flexible bronchoscope and can be located in
      second-order bronchial branches. Metallic stents have been used to treat benign
      airway obstruction caused by anastomotic narrowing after lung transplantation,
      infection, congenital lesions, tracheobronchial malacia, inflammatory conditions
      including relapsing polychondritis, Wegener granulomatosis, and acquired
      immunodeficiency syndrome, and external compression from benign mediastinal
      masses or fibrosis. The stents become epithelialized, which prevents migration
      and permits ciliary activity to continue. Significant complications can occur,
      including airway inflammation, stent migration, airway erosion, and stent
      fracture and collapse, but more serious complications are uncommon. Computed
      tomography is essential in imaging patients being considered for stent placement,
      as it allows 1) accurate representation of airway anatomy in three dimensions. 2)
      measurement of airway diameter, 3) evaluation of airway anatomy distal to a
      narrowed segment and invisible to bronchoscopy, 4) demonstration of dynamic
      changes in airway morphologic features during forced exhalation in patients with
      airway malacia, and 5) demonstration of focal or diffuse air trapping in lung
      peripheral to the abnormal airway. In patients who have had stent placement,
      computed tomography is valuable in assessing airway morphologic features and
      dynamics distal to the stent, and can be valuable in assessing stent dysfunction.

PMID- 9556290
TI  - Thoracic manifestations of sickle cell disease.
AB  - Sickle cell disease is the most common inherited disease in the African American
      population. Multiorgan pathologic features with a predilection for thoracic
      organs predominate. Acute cardiopulmonary diseases include acute chest syndrome,
      pneumonia, and left ventricular failure. Cardiomegaly, pleural effusions,
      pulmonary consolidation, pulmonary edema on chest radiographs, and ground-glass
      opacities on computed tomographs are characteristic. Chronic changes include
      sickle cell lung disease with lung fibrosis, pulmonary arterial hypertension,
      hyperkinetic circulation related to severe anemia, and thoracic skeletal
      abnormalities; the latter are H-shaped vertebrae, rib infarction, and
      extramedullary hematopoesis.

PMID- 9556291
TI  - Assessment of air trapping using postexpiratory high-resolution computed
      tomography.
AB  - The authors assess the utility of postexpiratory high-resolution computed
      tomography (HRCT) scans in the evaluation of air trapping in patients with
      obstructive lung disease. Thirteen healthy volunteers and 14 patients with
      obstructive lung disease (OLD) were examined using inspiratory and postexpiratory
      HRCT scans. All had pulmonary function tests. Lung attenuation was measured on
      both inspiration and expiration, and the extent of air trapping on postexpiratory
      scans was visually assessed. The results of the healthy volunteers were compared
      with those of patients with OLD, and HRCT findings were correlated with pulmonary
      function tests. Lung attenuation on expiration, its change from inspiration to
      expiration, and air-trapping scores of patients with OLD were significantly
      different from those of the healthy volunteers. When the healthy participants and
      patients with OLD were combined and analyzed as one group, the lung attenuation
      change and air-trapping score both significantly correlated with pulmonary
      function tests (p < 0.001) and correlation values were similar (r = 0.61-0.89).
      Air trapping was found in 61% of healthy participants and all the patients with
      OLD, although the extent was significantly greater in the patients with OLD.
      Inspiratory and postexpiratory HRCT can be used to evaluate air trapping in
      patients with OLD. Measurements of lung attenuation and estimates of air-trapping
      extent are both valuable methods of analysis.

PMID- 9556292
TI  - Muscular hypertrophy of the left diaphragmatic crus: an unusual cause of a
      paraspinal "mass".
AB  - We present a case of marked muscular hypertrophy of the muscular portion of the
      diaphragm and of the diaphragmatic crura in a professional opera singer. In this
      case the right and left crus each measured 20 mm in maximum thickness. The left
      crus, by nature of its vertical orientation in the sagittal plane, produced
      marked deviation of the inferior left paraspinal line near the diaphragm
      mimicking a retrocrural or paraspinal mass on the posteroanterior chest
      radiograph. The correct diagnosis was made by computed tomography. Muscular
      hypertrophy of the diaphragmatic crura should be included in the differential
      diagnosis of retrocrural or paraspinal masses at the level of the diaphragm.

PMID- 9556293
TI  - Fetal gender impact on multiple-marker screening results.
AB  - Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and
      unconjugated estriol (uE3) are used in combination with maternal age to calculate
      the risk for Down syndrome (DS) in pregnancy. Increased levels of hCG and
      decreased levels of MSAFP and uE3 are consistent with an increased risk for DS.
      We retrospectively evaluated second-trimester maternal serum marker levels in a
      large cohort of patients with known normal outcomes and documented fetal gender.
      These included 15,428 patients who had MSAFP measurements, 11,428 patients with
      both MSAFP and hCG, and 6,090 patients with all three markers including uE3.
      MSAFP levels in patients with female fetuses were consistently lower than those
      with males. Conversely, hCG was higher in pregnancies with females as compared to
      males. No gender-related difference was noted for uE3. These results would
      suggest that the computed DS risk for female fetuses is higher than for males,
      despite the fact that the incidence of DS is similar in both genders. This
      information could be useful for calculating gender-specific DS risk; however,
      this would require ultrasonographic determination of fetal sex.

PMID- 9556294
TI  - Chromosome 18q paracentric inversion in a family with mental retardation and
      hearing loss.
AB  - We report on a mother and child with a paracentric inversion of the long arm of
      chromosome 18: 46,XX,inv(18)(q21.1q23). The child had findings in common with
      those seen in 18q- syndrome including: microcephaly, epicanthal folds, midface
      hypoplasia, and abnormally modeled ears, dermatoglyphic whorls on fingertips,
      clubfeet, hearing loss, and developmental delay. The mother and several maternal
      relatives had mild mental retardation and hearing loss. Magnetic resonance
      imaging of the child's brain showed abnormal myelination. Molecular studies
      including PCR-based markers for the MBP locus and fluorescent in situ
      hybridization with a P1 genomic clone on mother and child demonstrated only one
      copy of the MBP locus (18q23) with the deletion extending beyond the MBP locus.
      Therefore, the deletion in the MBP region may account for the abnormal
      myelination seen in the patient. The other clinical findings, including mental
      retardation and hearing loss in this family, may reflect disruption of distal or
      proximal genes within the deleted MBP region or at the more proximal breakpoint
      18q21.1, and may represent a contiguous gene syndrome. Further study of this
      family may help define those genes functioning in the MBP region that contribute
      to the phenotype of 18q- syndrome.

PMID- 9556295
TI  - Identification of a mutation in the low density lipoprotein receptor gene
      associated with recessive familial hypercholesterolemia in swine.
AB  - Elevated blood plasma cholesterol (hypercholesterolemia) is a major risk factor
      for coronary artery disease (CAD) in humans. Genetic dissection of polygenic
      lipid and lipoprotein disorders in swine, a key animal model for the study of
      familial hypercholesterolemia (FH) and CAD, led to the isolation of a monogenic
      subphenotype (FH-r), that is inherited in the recessive (r) manner. A genome scan
      mapped the FH-r locus close to the centromere of chromosome 2. Comparative
      mapping showed that this region shares homology with a part of human chromosome
      19 that harbors the low density lipoprotein receptor (LDLR) locus, and therefore
      suggested LDLR as the prime candidate gene for FH-r. Cloning and sequencing of
      hepatic LDLR cDNA from two FH-r/r and one normal (N/N) animals disclosed a single
      missense mutation (R84C) in a region that corresponds to human exon 4. The C84
      mutation cosegregates invariantly with hypercholesterolemia, which strongly
      suggests that this mutation is responsible for the observed hyperlipidemia.

PMID- 9556296
TI  - Cohen syndrome with high urinary excretion of hyaluronic acid.
AB  - Cohen syndrome (MIM 216550) is an autosomal recessive disorder of unknown
      pathogenesis. The clinical manifestations of Cohen syndrome can be explained as a
      connective tissue disorder. We found a remarkably high level of urinary
      hyaluronic acid in 3 patients with Cohen syndrome. Hyperhyaluronic aciduria is a
      characteristic finding in Werner syndrome and some other conditions. We suggest
      that the basic defect of Cohen syndrome is associated with a metabolic
      abnormality in the extracellular matrix.

PMID- 9556297
TI  - Unclassified sclerosing bone dysplasia with osteopathia striata, cranial
      sclerosis, metaphyseal undermodeling, and bone fragility.
AB  - Sclerosing bone dysplasias are diagnosed on the basis of a characteristic pattern
      of osteosclerosis and clinical manifestations; in many of them, cause and
      pathogenesis are still unknown. A 33-year-old man had five fractures of the
      humerus, tibiae, and femur as a result of mild traumatic incidents that occurred
      between the ages of 18 and 33 years as well as a remnant of rib fractures without
      apparent trauma on radiographs. His height was 158 cm (-2.2 SD). Radiographic
      evaluation showed cranial sclerosis, longitudinal striations in the metaphyses of
      the femur and tibia, fan-like striation in the ilium, metaphyseal widening in the
      femur and tibia, and sclerosis of the ribs. The blood chemistry findings,
      including serum calcium, phosphorus, and alkaline phosphatase, were normal.
      Biopsy from the ilium showed thick trabeculae composed of woven bone. The
      coexistence of osteopathia striata, cranial sclerosis, metaphyseal undermodeling,
      and bone fragility has not been recognized previously. Our case appears to
      represent a new form of sclerosing bone dysplasia.

PMID- 9556298
TI  - Autosomal-dominant branchio-otic (BO) syndrome is not allelic to the branchio-oto
      renal (BOR) gene at 8q13.
AB  - The manifestations of branchio-oto-renal syndrome (BOR), Treacher Collins
      syndrome, tricho-rhino-phalangeal syndrome, van der Woude syndrome, and Langer
      Giedion syndrome are well-defined; these conditions represent clinically and
      genetically separate syndromes. Autosomal-dominant branchio-oto-renal syndrome
      comprises preauricular pits, branchial fistulas, hearing loss, and renal
      anomalies. However, several families have been described without one or more of
      these clinical findings. In some families, the phenotypic expression is limited
      to branchial anomalies, preauricular pits, and hearing loss, with no renal
      dysplasia (branchio-otic or BO syndrome). In other families, branchial and renal
      anomalies occur without hearing impairment. It is not known whether the variable
      clinical manifestations are due to the effect of a single gene or whether these
      represent different syndromes. We investigated BO syndrome in a large family to
      determine whether BOR and BO syndromes are allelic to each other. The genetic
      linkage analysis provides evidence that BO syndrome is not allelic to the BOR
      gene at 8q13.

PMID- 9556299
TI  - CHARGE syndrome: report of 47 cases and review.
AB  - The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47
      CHARGE patients evaluated for the frequency of major anomalies, namely coloboma
      (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental
      retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness
      (62%). In addition, we comment on anomalies observed very frequently in neonates
      and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal
      brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear
      anomalies such as semicircular canal hypoplasia that were found in each patient
      that could be tested. We propose several criteria for poor survival including
      male gender, central nervous system and/or oesophageal malformations, and
      bilateral choanal atresia. No predictive factor regarding developmental prognosis
      could be identified in our series. A significantly higher mean paternal age at
      conception together with concordance in monozygotic twins and the existence of
      rare familial cases support the role of genetic factors such as de novo mutation
      of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally,
      the combination of malformations in CHARGE syndrome strongly supports the view
      that this multiple congenital anomalies/mental retardation syndrome is a
      polytopic developmental field defect involving the neural tube and the neural
      crests cells.

PMID- 9556300
TI  - Spondylometaphyseal dysplasia-Sedaghatian type.
AB  - We present the radiological findings in two unrelated cases with
      spondylometaphyseal dysplasia type Sedaghatian. We review the literature and
      identify additional anomalies including disproportionately long fibulae,
      dysharmonious maturation and turricephaly.

PMID- 9556301
TI  - Incidence of X-linked adrenoleukodystrophy and the relative frequency of its
      phenotypes.

PMID- 9556302
TI  - X-linked adrenoleukodystrophy: the Australasian experience.
AB  - Our objective was to review the Australasian experience of X-linked
      adrenoleukodystrophy (ALD), to compare the spectrum of disease seen in
      Australasia with previously published data from elsewhere, and to assess the
      reliability of carrier testing. Study design was a retrospective review of
      records collected over a 15-year period, the setting was an international
      referral laboratory for the study of metabolic disease, and the subjects were all
      known cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996
      and their families. We estimate that the combined incidence of ALD and its
      variants in Australasia is at least 1.6 per 100,000. Of 95 affected males, 51 had
      cerebral adrenoleukodystrophy, 24 had adrenomyeloneuropathy, 15 had Addison's
      disease only, and 5 remained asymptomatic when last examined. However, the
      distribution of phenotypes among newly diagnosed patients has changed
      substantially over the last 15 years, with cerebral forms of the disease forming
      a decreasing proportion of new diagnoses. The measurement of plasma very long
      chain fatty acids (VLCFAs) alone detects 93% of women who can be proven to be
      carriers. The addition of genetic linkage studies or assay of VLCFAs in cultured
      fibroblasts improved this detection rate to the point that there were no obligate
      carriers who could not be detected using a combination of two or more techniques.

PMID- 9556303
TI  - X-linked adrenoleukodystrophy: phenotype distribution and expression of ALDP in
      Spanish kindreds.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by
      an impairment in peroxisomal beta-oxidation of very long straight-chain fatty
      acids (VLCFAs). Six clinical phenotypes have been delineated: childhood cerebral
      (CCALD), adolescent cerebral (AdolCALD), adult cerebral (ACALD),
      adrenomyeloneuropathy (AMN), Addison-only (AO), and presymptomatic (PALD). The
      distribution of phenotypes varies in different countries. We have diagnosed
      biochemically 60 X-ALD Spanish patients belonging to 48 kindreds. Their
      phenotypic distribution was: CCALD plus AdolCALD, 33%; ACALD, 16%; AMN, 27%; AO,
      12%; and PALD, 12%. These results contrast with the distribution described in
      other countries, due to a higher prevalence of the ACALD form. Regarding the
      expression of the protein product (ALDP), we studied 17 kindreds using
      immunochemical techniques and found absence of ALDP in 84% of cases. We also
      studied 13 females from 7 negative ALDP kindreds in order to correlate ALDP
      expression and the carrier status established by VLCFA measurement. In one case
      with normal VLCFA levels in serum and fibroblasts, we observed mosaicism in ALDP
      expression. This fact supports the use of this technique for identifying
      carriers.

PMID- 9556304
TI  - A multivariate logistic model (MLM) for analyzing binary family data.
AB  - We consider modeling the familial correlation between 2 related individuals using
      a multiple logistic regressive model. It is shown that there is a discrepancy in
      the marginal probability of the second individual. We investigate the conditions
      under which this discrepancy can be minimized and show how it can have a direct
      effect on handling missing values and ascertainment. We derive a functional
      relationship between the parameters in the model that eliminates this
      discrepancy, hence solving the problems that can arise in the handling of missing
      values and ascertainment. Because this methodology fails when there are more than
      2 related individuals, we present a new model based on a multivariate logistic
      distribution. Residual familial correlations can be directly related to the
      parameters of this model. The likelihood for family data under this model is
      independent of the order in which the family members enter the calculation. The
      marginal probabilities can be easily computed.

PMID- 9556305
TI  - Founder effect in GLC1A-linked familial open-angle glaucoma in Northern France.
AB  - Open-angle glaucoma (POAG) is a highly prevalent cause of visual impairment. Six
      families grouping 71 living patients affected with juvenile-onset and middle-age
      POAG (age at diagnosis ranging from 10 to 65 years) were linked to the GLC1A
      locus. All patients carried a mutation of an evolutionarily conserved asparagine
      residue to a lysine at position 480 (N480K) in the olfactomedin-homology domain,
      which is encoded by the third exon of the GLC1A gene. The N480K mutation was also
      identified in 14 unaffected carriers who are at high risk of developing POAG.
      Although four of the families had ancestors identified in Northern France, the
      pedigrees could not be interconnected by genealogical investigation. However,
      haplotype analysis indicated that all the carriers had inherited the N480K
      mutation from the same founder. Screening of a selected set of 67 POAG patients
      who originated from Northern France and underwent trabeculectomy before the age
      of 50, detected one patient with the N480K mutation associated with the same
      disease haplotype already characterized in the 6 families. This group of 72 POAG
      patients is the largest one having a GLC1A mutation in common and provides a
      unique tool to investigate the factors influencing the variable expressivity of
      the GLC1A gene.

PMID- 9556306
TI  - Pulmonary agenesis: importance of detailed cytogenetic studies.

PMID- 9556307
TI  - Mosaic trisomy 22: a case presentation and literature review of trisomy 22
      phenotypes.

PMID- 9556308
TI  - Acceleration of partial-thickness burn wound healing with topical application of
      heparin-binding EGF-like growth factor (HB-EGF).
AB  - Heparin-binding EGF-like growth factor has been identified in human burn-wound
      fluid and in the epithelial cells of excised human partial-thickness burns. In
      the present study, the effect of heparin-binding EGF-like growth factor on burn
      wound healing was evaluated by incorporating purified, recombinant heparin
      binding EGF-like growth factor into slow-release cholesterol-lecithin pellets
      that were applied topically to partial-thickness burns in mice. Both experimental
      (heparin-binding EGF-like growth factor-treated) and control (untreated) mice
      were sacrificed on days 3, 5, and 10 after burn. Total burn-wound area,
      histology, keratinocyte proliferation, and in situ hybridization analysis for
      transforming growth factor-alpha were determined for each wound. The mean wound
      area of the experimental group on day 5 after burn was 1.07 cm2, compared with
      2.20 cm2 for controls (p=0.04). Cellular proliferation (as measured by
      immunohistochemical detection of 5-Bromo-2-deoxyuridine) on day 5 after burn in
      marginal keratinocytes and follicular epithelial cells was greater in the
      experimental group than in the control group. In situ hybridization showed up
      regulation of transforming growth factor-alpha mRNA levels in experimental
      animals by day 5 after burn. Topical application of heparin-binding EGF-like
      growth factor significantly accelerates the reepithelialization of murine partial
      thickness burns, increases keratinocyte proliferative activity, and enhances
      production of endogenous transforming growth factor-alpha mRNA.

PMID- 9556310
TI  - Calorigenic response of burned rats with adrenal medullectomies to
      catecholamines.
AB  - In previous studies, we established that circulating epinephrine (E) is not
      essential for a normal hypermetabolic response to burn injury in the rat, within
      the zone of thermal neutrality. In other studies, burned rats with adrenal
      medullectomy (AdxB) studied at 22 degrees C were unable to maintain rectal
      temperature (TR) after alpha-adrenergic blockage. These data suggest that
      norepinephrine (NE) is calorigenic in such animals without formal cold
      acclimation. These studies investigate the hypothesis that, contrary to the usual
      belief, norepinephrine might be calorigenic in rats without formal cold
      acclimation. Burned (B) and control (C) rats with adrenal medullectomies (Adx)
      and Sham (S) Adx (AdxB, SAdxB, AdxC, and SAdxC) were housed at either 22 degrees
      C or 28 degrees C. Calorimetry was performed during the eighth to eleventh days
      after the burn. For groups housed at 22 degrees C and studied at 28 degrees C, NE
      given intravenously (iv) produced an average 16.5%+/-3.3% increment in heat
      production (HP) for the four groups, which was significant for AdxB, SAdxB, and
      SAdxC. Intravenous administration of E produced an average increment in HP of
      4.44%+/-4.1%, which was not significant. HP was significantly higher after NE
      than E in three cases. Studies with animals housed at 28 degrees C and studied at
      28 degrees C produced intermediate but similar results. For groups housed at 28
      degrees C and studied at 22 degrees C, iv administration of E and NE produced
      average decreases in He of 18%+/-6.7% for E and 10.75%+/-4.7% for NE. Except for
      the AdxC group, these differences were significant. These data suggest that
      chronic exposure to an ambient temperature of 22 degrees C produces an enhanced
      calorigenic response to NE in burn and control rats. Based on the data presented
      here, combined with earlier studies, NE must be considered as a facilitator for
      hypermetabolic response to burn injury in the rat. It is interesting to speculate
      whether NE is calorigenic for patients with large burn wounds, which are managed
      without dressings at ambient temperatures below thermal neutrality.

PMID- 9556309
TI  - Efficacy of a rise in C-reactive protein serum levels as an early indicator of
      sepsis in burned children.
AB  - C-Reactive protein serum levels were measured in 57 pediatric patients with 3% to
      92% total body surface area burns to determine whether a defined rise in C
      reactive protein serum levels could indicate sepsis earlier in burn patients. A
      rise in C-reactive protein serum levels was defined as an increase of at least 3
      mg/dL for 2 days or 10 mg for 1 day. Increases the first 2 days after the burn or
      the day after surgery were excluded, since these injuries increase C-reactive
      protein serum levels. Patients were defined as septic when they were on systemic
      antibiotics and exhibited at least two of 16 specific clinical parameters. C
      Reactive protein serum levels correctly predicted sepsis 82% of the time
      (efficiency=82%). Nonseptic patients generally did not show increased C-reactive
      protein serum levels (specificity=69%). When sepsis did occur, it always was
      preceded by increased C-reactive protein (sensitivity=100%), and the increased C
      reactive protein occurred 2.3+/-0.5 days before the patient was deemed septic
      clinically. Hence, a defined rise in C-reactive protein serum levels can predict
      sepsis sooner in burned children.

PMID- 9556311
TI  - Treatment of the seriously burned infant.
AB  - Infants (younger than 12 months) with large (more than 30%) burns are reported to
      have poorer chances for survival than older children with similar injuries.
      However, recent experience with such infants has been positive, prompting a 5
      year review of management techniques. The injuries were approached in an
      organized fashion that included precise fluid support, excision, and biologic
      closure of full-thickness wounds within 5 days, limited exposure to high
      inflating pressures (more than 40 cm H2O), weekly replacement of central venous
      catheters, and intensive nutritional support via the enteral route whenever
      possible. Twelve such infants were treated during the 5-year interval. Their
      average age was 7.8 months (range, 1 to 12 month[s]), average weight was 8.8 kg
      (range, 4.3 to 13 kg), and average burn size was 42% (range, 30% to 90%).
      Inhalation injury was present in two of the children, and one child aspirated hot
      liquid. Six (50%) of the infants required the support of a mechanical ventilator
      for an average of 11.6 days (range, 4 to 18 days). Eight children required an
      average of 5.7 operations (range, 1 to 18 operation[s]), seven required central
      venous catheters, and five required arterial cannulae. Major infectious
      complications were seen in four children. Complications included pneumonia (two),
      catheter sepsis (two), peritonitis from a perforated ulcer (one), and wound
      sepsis (two). Six children required parenteral nutritional support for an average
      of 15 days (range, 5 to 36 days), and six children required enteral tube feedings
      for an average of 23 days (range, 9 to 55 days). Anabolic agents were not used.
      Discharge weights averaged 8.6 kg (range, 4.9 to 10.5 kg). The average ratio of
      the children's discharge to admission weight was 101% (range, 73% to 120%). All
      children survived and were discharged home. We conclude that these difficult
      injuries can be approached successfully with a strategy that emphasizes precise
      fluid repletion; early excision and biologic closure of wounds; avoidance of
      ventilator-induced lung injury; and intensive nutritional support.

PMID- 9556312
TI  - Purpura fulminans: a disease best managed in a burn center.
AB  - Victims of purpura fulminans are overcome by a rapidly progressive and sometimes
      fatal course involving large amounts of tissue loss and multiple organ system
      failure. From 1986 to 1995, seven children ranging in age from 10 months to 19
      years (mean, 6.2 years) were referred to the Shriners Burns Institute in
      Cincinnati with purpura fulminans. Neisseria meningitidis was identified as the
      precipitating pathogen in most of the patients. The mean TBSA full-thickness skin
      loss was 33%. Fourteen extremities were amputated in the seven patients,
      including three patients with amputations of all four extremities. Transfer to
      our institution occurred after a mean delay of 20 days, usually after the
      demarcation of viable tissue. In one patient, however, fasciotomies obviated
      multiple impending amputations. Monitoring for elevated compartment pressures,
      early fasciotomies, and expedient transfer to a burn center for a
      multidiciplinary approach to care should improve the outcome in patients with
      purpura fulminans.

PMID- 9556313
TI  - Children with sensorimotor deficits: a special risk group.
AB  - Children with spina bifida, cerebral palsy, mental retardation, developmental
      delays, and seizure states are handicapped with sensorimotor deficits, including
      gait or coordination instability, temperature insensitivity, and mental
      simplicity. These handicaps make this distinct and unpretentious population more
      susceptible to lethal burns. A 30-year review was conducted in a pediatric burn
      center to examine the relationships between pediatric sensorimotor deficit and
      burn injury. Of the 4874 acute burn admissions, 66 children were identified with
      preexisting sensorimotor deficits. Data indicate that children with sensorimotor
      deficit are more prone to burn injury from both their physical impairment and
      poorly supervised environments. In addition to extended hospitalizations, these
      children bear significantly higher mortality risks. Had the special supervisions
      and protection required by such handicapped children been provided, 80% of the
      burn injuries could have been prevented. Results emphasize that the future of
      these special children with sensorimotor deficits relies on health care providers
      playing a greater role in educating parents and caregivers.

PMID- 9556314
TI  - Hot-press hand burn treatment.
AB  - Hand injuries are common in the workplace. Modern industrial machines cause
      complex occupational hand injuries. Hot-press contact hand burns generally are
      encountered by workers in the dry-cleaning industry. Seventeen patients with hot
      press hand burns were treated at the University of California-Irvine Medical
      Center Burn Center. Eight patients (47%) required skin grafting, seven (41%) were
      treated with hydrotherapy only, and two (12%) needed flaps. These results were
      not what we expected.

PMID- 9556315
TI  - Extracorporeal membrane oxygenation in the treatment of respiratory failure in
      pediatric patients with burns.
AB  - Extracorporeal membrane oxygenation (ECMO) as a treatment for pulmonary failure
      from postshock respiratory distress in burned children recently has been shown to
      salvage patients who were thought to have more than a 90% chance of dying. We
      describe five burned children in whom severe respiratory failure--not responsive
      to medical management and maximal ventilatory support--developed, and who
      underwent ECMO treatment. Three (60%) cases involved flame burns, with
      significant inhalation injury as diagnosed after a bronchoscopy; mean age was 3
      years (2 to 4 years), with a mean total body surface area (TBSA) burn of 32% (15%
      to 53%), mean third-degree burns of 25% (5% to 53%). Two (40%) cases involved
      scald burns; mean age was 6 years (7 months to 11 years), with a mean TBSA burn
      of 56.5% (43% to 70%), mean third-degree burns of 40% (10.5% to 70%). Outcome was
      poor for those burned children who received ECMO therapy after prolonged
      ventilatory support for smoke inhalation injury. Children who experience
      perfusion/reperfusion shock injury to the lungs as a result of delayed
      resuscitation of scald burns may have an improved chance of survival with short
      courses of ECMO regardless of the burn size.

PMID- 9556316
TI  - Hemolytic uremic syndrome in a child with burn injuries.
AB  - We report the first case of hemolytic uremic syndrome in a patient with burns. An
      unusual case of the syndrome developed in a 1-year-old black girl hospitalized
      after second-degree burns to 33% of her total body surface area. Acute abdominal
      distention, hemolytic anemia, hematuria, and oliguric renal failure developed 1
      week after admission to the burn unit. Blood cultures grew Escherichia coli
      O157:H7. She received supportive care and antibiotics, in addition to low-dose
      dopamine, which promptly reversed the oliguria. Dialysis was not required, and
      the child made a complete recovery.

PMID- 9556318
TI  - Continuous infusion of epidural morphine in frostbite.
AB  - After frostbite injury, the phases of rewarming and progressive injury may cause
      intense pain for the patient. Although parenteral narcotic agents are the usual
      method of pain relief, they have well-described adverse effects such as heavy
      sedation, respiratory depression, and nausea and vomiting. In frostbite injury of
      the lower extremities, epidural blockade has the potential to provide good pain
      relief with fewer of those complications. However, the associated sympathetic
      blockade is believed by many clinicians to be of no benefit and by some to be
      potentially harmful. Epidural narcotics have the selective advantage of providing
      analgesia without sympathetic blockade. In this case report, the use of
      continuous epidural morphine during the first 24 hours after severe bilateral
      frostbite injury to the feet is described. The technique provided effective pain
      control, and no complications occurred. To our knowledge, use of continuous
      epidural morphine after frostbite injury has not been reported previously.
      Further use of this technique will be required to clarify its efficacy.

PMID- 9556317
TI  - HIV seropositivity in a burn center's population.
AB  - HIV infection in a patient with burn injuries complicates the care of both the
      patient and the treating burn team. In the patient, HIV slows wound healing and
      increases the complications seen with burns. For the treating team, HIV is a
      hazard that infects the large volume of bodily fluids to which the burn team is
      potentially exposed. At Saint Francis Memorial Hospital, a team of plastic
      surgeons, infectious disease specialists, medical internists, psychiatrists,
      social workers, and nurses was established for the care of patients with burn
      injuries who have HIV. To ascertain the baseline need for this specialized care,
      we interviewed 103 consecutive patients admitted to the Bothin Burn Center. Those
      found to be positive by history (3 of 103) were excluded from HIV testing. Of the
      remaining 100 consecutive patients, all consented to HIV testing. None of these
      patients, even those with known risk factors, was found to have undiagnosed HIV
      positivity. We conclude the occult incidence in the population tested is lower
      than expected, and continued testing is warranted.

PMID- 9556319
TI  - Proceedings of the physical and occupational therapy special interest group
      meeting.
AB  - At the 1997 American Burn Association meeting in New York City the Physical
      Therapy/ Occupational Therapy (PT/OT) Special Interest Group met and discussed
      five pertinent topics that affect therapists. A summary of the information was
      received from the five discussion groups. This information is presented so that
      the entire PT/OT membership can be kept informed and updated about the
      information presented at this meeting. Moderators can be resources for more in
      depth information regarding these topics.

PMID- 9556320
TI  - Burn pain management: a guideline-based approach.
AB  - The pain associated with burn injury and treatment often is managed poorly. The
      purpose of this article is to describe available pain-management guidelines and
      to explain how burn pain can be enhanced by using a guideline-based approach.
      Data from a retrospective audit are used to highlight several of the common
      causes of pain mismanagement: including inadequate pain assessment, analgesic
      knowledge deficits, and incomplete documentation. Key recommendations from the
      Agency for Health Care Policy and Research's Acute Pain Management Guidelines are
      highlighted. Guideline-based suggestions from these and other guidelines are
      presented as a basis for burn pain management-guideline development. Guidelines
      for burn-pain management must be broad in scope to allow for variations in
      analgesic needs across all patient populations and phases of burn recovery.
      Guidelines are necessary because studies show that information and education
      alone have little effect on the quality of pain management. What is effective are
      guideline-based initiatives that make pain visible and care providers
      accountable.

PMID- 9556321
TI  - Increased protein intake during the recovery phase after severe burns increases
      body weight gain and muscle function.
AB  - We determined the effect of protein intake on weight gain and muscle function in
      the recovery phase after severe burns. Fifteen patients with deep burns between
      30% to 50% of total body surface were studied over a 3 week period-after
      resolution of the hypermetabolic, catabolic state. All patients were studied in
      an acute rehabilitation hospital affiliated with the burn center. Nutritional
      profiles; weight gain; and muscle strength, measured by a physical therapy index
      (0 to 10)--10 being the greatest progress-were measured. All patients were
      provided a high-calorie, high-protein diet. Group 1 patients (n=8) also were
      provided a standard nutrient supplement to maintain caloric intake at 30 to 35
      kcal/kg/day and to maintain protein intake at 1.3 to 1.5 g/kg/day. Group 2
      patients (n=7) were provided a high-calorie, high-protein diet plus a protein
      hydrolysate (70 g/day) that provided a protein intake of 1.7 to 2 g/kg/day. Group
      1 patients averaged a 1 to 1.5 pound weight gain per week or four pounds during
      three weeks. Their physical therapy index at three weeks of 4+/-0.5 indicated
      adequate improvement in strength and endurance. Group 2 patients averaged 2.5 to
      3 pounds weight gain per week or 8.5 pounds during three weeks. Their physical
      therapy index of 7+/-0.7 indicated marked gains in muscle strength. Both
      measurements were significantly higher than those of Group 1. We conclude that
      increased protein intake by means of adding a protein hydrolysate increases the
      rate of restoration of body weight and muscle function.

PMID- 9556322
TI  - Rehabilitation challenges for burn survivors with residual disfigurement:
      promising directions for intervention, research, and collaboration.

PMID- 9556323
TI  - Changing Faces: Taking up Macgregor's challenge.
AB  - I had the good fortune to initially present the thoughts written here at the
      Psychosocial Interest Group of the American Burn Association Annual Meeting in
      New York City in 1997. The paper begins with a personal introduction and proceeds
      to describe how Frances Cooke Macgregor's work inspired my colleagues and myself
      to develop a series of programs to address the rehabilitation challenges inherent
      in living with any kind of facial disfigurement. It is our sincere hope that the
      programs developed by our organization, Changing Faces (based in the United
      Kingdom) will contribute to the rehabilitation of people living with
      disfigurement throughout the world. We especially look forward to learning how
      what we have learned can be adapted to and disseminated in the United States as
      we establish collaborative relationships with the dedicated group of burn
      professionals there.

PMID- 9556324
TI  - Silipos neck wraps.
AB  - Burns of the neck are a problem. Grafted anterior necks can result in disfiguring
      hypertrophic scar contractures and wrinkling of the graft. The development of
      contractures can be prevented by effective splinting as soon as possible after
      the burn and by following a continuous wearing schedule until scar maturation is
      complete. Traditional neck conformers do not allow free neck rotation and can
      lead to stiffness as a result of decreased mobility. We used Silipos neck wraps
      for 10 patients who had good range of motion in the neck and who required
      pressure only for flattening of grafts and wrinkle prevention. The neck wrap is
      user-friendly, low in cost, and easy to fabricate and custom-fit for individual
      patients.

PMID- 9556325
TI  - Reliability of photographic analysis in determining change in scar appearance.
AB  - Photographs frequently are used to document change in the management of
      hypertrophic scars. The purpose of this study was to design a scale for the
      analysis of photographs of hypertrophic scars and to test its reliability. The
      subjects were four occupational and physical therapists, (two novices and two
      experts), in scar management. Existing scales were modified to produce a new
      scale. The subjects twice rated four slides from each of ten patients' scars, in
      random order. They used a Latin Square design. Interrater and test-retest
      reliabilities were calculated using a weighted kappa statistic. The newly
      developed scale demonstrated interrater reliability, which ranged between 0.66
      and 0.90 for all items. The test-retest reliability ranged between 0.73 and 0.89
      for all items. The new scale had substantial reliability (using a single rater)
      and was at least as reliable when used by novice therapists. This indicated that
      training had no effect.

PMID- 9556326
TI  - Incorrect comparison relating test MICs and clear zone diameter by use of NAWD.

PMID- 9556327
TI  - Functions of motor proteins in echinoderm embryos: an argument in support of
      antibody inhibition experiments.
AB  - Antibody inhibition experiments are proving to be extremely valuable in probing
      the in vivo functions of actin- and microtubule-based motor proteins in the early
      development of echinoderm embryos, despite some skepticism among many cell
      biologists concerning the reliability of this approach. Antibody inhibition has
      revealed that motor proteins participate in diverse events during early
      echinoderm development, including mitosis, cytokinesis, the transport of
      exocytotic vesicles, and the assembly of motile cilia.

PMID- 9556328
TI  - Dynein and dynein-related genes.
AB  - Dyneins are large, multisubunit ATPases that interact with microtubules to
      generate force. Dyneins move eukaryotic cilia and flagella and are in the
      cytoplasm, where they are involved in the transport of particles and organelles
      along microtubules and in the transport of condensed chromosomes during mitosis
      [reviewed in Holzbaur et al., 1994; Gibbons, 1996]. Defects in human axonemal
      dynein complexes have been shown to be associated with Kartagener's syndrome,
      which is characterized by recurrent respiratory tract infections, immotile sperm
      and situs inversus. Cytoplasmic and axonemal dyneins are composed of heavy,
      intermediate, and light chains. The best characterised groups of dynein genes so
      far are those encoding cytoplasmic heavy chains and heavy chains from the outer
      arms from axonemes. These share extensive sequence similarity and are conserved
      throughout species. Recently, several genes encoding intermediate and light
      chains have been identified; these have encoded a remarkable diversity of
      products, which also seem to be highly conserved between species, although they
      fall into several complex groups. The structure of dynein heavy chain genes, the
      emerging knowledge on intermediate and light chain genes and their products, and
      the possible involvement of dyneins in disease are discussed.

PMID- 9556329
TI  - Depletion of a Drosophila homolog of yeast Sup35p disrupts spindle assembly,
      chromosome segregation, and cytokinesis during male meiosis.
AB  - In the course of a genetic screen for male-sterile mutations in Drosophila
      affecting chromosome segregation during the meiotic divisions in spermatocytes,
      we identified the mutation dsup35(63D). Examination of mutant testes showed that
      chromosome misbehavior was a consequence of major disruptions in meiotic spindle
      assembly. These perturbations included problems in aster formation, separation,
      and migration around the nuclear envelope; aberrations in spindle organization
      and integrity; and disappearance of the ana/telophase central spindle, which in
      turn disrupts cytokinesis. The dsup35(63D) mutation is caused by a P element
      insertion that affects, specifically in the testis, the expression of a gene
      (dsup35) encoding the Drosophila homolog of the yeast Sup35p and Xenopus eRF3
      proteins. These proteins are involved in the termination of polypeptide synthesis
      on ribosomes, but previous studies have suggested that Sup35p and closely related
      proteins of the same family also interact directly with microtubules. An affinity
      purified antibody directed against the product of the dsup35 gene was prepared;
      interestingly, this antibody specifically labels primary spermatocytes in one or
      two discrete foci of unknown structure within the nucleoplasm. We discuss how
      depletion of the dsup35 gene product in spermatocytes might lead to the global
      disruptions in meiotic spindle assembly seen in mutant spermatocytes.

PMID- 9556330
TI  - Structural and molecular characterization of dynein in a gall-midge insect having
      motile sperm with only the outer arm.
AB  - The dipteran Monarthropalpus flavus possesses a peculiar sperm axoneme,
      characterized by multiple rows of microtubular doublets linked by the outer
      dynein arms only, lacking any equivalent of the central pair/radial spoke
      complex. The structure of these dynein molecules was studied by electron
      microscopy (EM). Using the quick-freeze, deep-etch method of EM, they were found
      to be similar to outer dynein arms described previously. Two globular "heads,"
      each subdivided by a cleft, are clearly discernible. "Stalks" extend from
      proximal head to contact the B-tubule of the adjacent doublet. Unlike the
      situation in vertebrate sperm, the stalks sometimes branch into two thinner
      strands that contact the B-tubule at different sites. Treatment of demembranated
      sperm cells with ATP and vanadate induces conformational changes in the dynein
      outer arms. These are interpreted as the result of rotation of the dynein head
      with respect to what is observed in axonemes in rigor condition (after ATP
      depletion). SDS-PAGE indicates that the high-molecular-weight complement of this
      molecule comprises a single heavy chain. Specific dynein heavy chain-related DNA
      sequences corresponding to the catalytic-phosphate binding region were amplified
      by RT-PCR. Only one axonemal dynein sequence was identified among all amplified
      fragments. Southern blot analysis performed on genomic DNA using this sequence as
      a probe identified two hybridizing genes, only one of which is able to encode a
      functional product. Thus, genetic analysis indicates that this axonemal outer arm
      dynein is a homodymer of a single heavy chain subunit. In vivo, spermatozoa of
      this species are stored in a rolled configuration in female spermatheca, where
      they move rapidly with a wave-like motion. This movement could not be reproduced
      in vitro, except when spermatozoa were constrained in a bent configuration by
      some mechanical impediment. We propose that, in the absence of both the central
      pair/radial spoke complex and the inner arms, a curvature-dependent activation
      acts to trigger motility in these spermatozoa.

PMID- 9556331
TI  - Tubulin polyglycylation in Platyhelminthes: diversity among stable microtubule
      networks and very late occurrence during spermiogenesis.
AB  - The distribution of glycylated tubulin has been analyzed in different populations
      of stable microtubules in a digenean flatworm, Echinostoma caproni
      (Platyhelminthes). Two cellular types, spermatozoa and ciliated excretory cells,
      have been analyzed by means of immunofluorescence, immunogold, and immunoblotting
      techniques using two monoclonal antibodies (mAbs), AXO 49, and TAP 952,
      specifically directed against differently glycylated isoforms of tubulin. The
      presence of glycylated tubulin in the two cell types was shown. However, the
      differential reactivities of TAP 952 and AXO 49 mAbs with the two axoneme types
      suggest a difference in their glycylation level. In addition, within a single
      cell, the spermatozoon, cortical microtubules underlying the flagellar membrane,
      and axonemal microtubules were shown to comprise different tubulin isoforms, the
      latter ones only being labelled with one of the antiglycylated tubulin mAbs, TAP
      952. Similarly, the antiacetylated (6-11B-1) and polyglutamylated (GT335) tubulin
      mAbs decorated the two types of axonemal microtubules, but not the cortical ones.
      From these data, a subcellular sorting of posttranslationally modified tubulin
      isoforms within spermatozoa, on the one hand, and a cellular sorting of
      glycylated isoforms inside the whole organism, on the other hand, is demonstrated
      in the flatworm E. caproni. Last, a sequential occurrence of tubulin
      posttranslational modifications was observed in the course of spermiogenesis.
      Acetylation appears first, followed shortly by glutamylation; glycylation takes
      place at the extreme end of spermiogenesis and, specifically, in a proximo-distal
      process. Thus in agreement with, and extending other studies [Bre et al., 1996],
      glycylation appears to close the sequence of posttranslational events occurring
      in axonemal microtubules during spermiogenesis.

PMID- 9556332
TI  - Derivation of insertin.
AB  - Insertin is an actin-binding protein that has been isolated from chicken gizzard
      smooth muscle that has been shown to be highly homologous to amino acids 962-1292
      of tensin [Weigt et al., 1992]. Because of the high homology, we investigated the
      question whether the mRNAs of insertin and of tensin are derived from the same
      gene by alternative splicing, whether insertin and tensin are encoded by two
      different genes, or whether insertin is a proteolytic fragment of tensin. In a
      Northern blot analysis, mRNA from chicken gizzard was hybridized with
      oligonucleotides specific for tensin and for the insertin domain of tensin. The
      tensin-specific oligonucleotide hybridized only with the previously reported 8-
      and 10-kbp RNAs. However, the insertin domain-specific oligonucleotide hybridized
      with a 1.2 and a 1.6 kbp RNA in addition to the 8 and 10 kbp RNA. The 1.2- and
      1.6-kbp RNA occurred in small amounts, as compared with the 8- and 10-kbp RNA.
      Southern blot analysis of DNA cleaved by the restriction endonucleases BamH1 and
      HindIII demonstrated that only one gene for the insertin and tensin exists.
      Insertin isolated from chicken gizzard smooth muscle was investigated by mass
      spectrometry. The N-termini of three isolated peptides were found to begin at
      adjacent amino acids and were likely to be formed from tensin by proteolysis. The
      results suggest that, for insertin, an mRNA exists that is derived from one gene
      common for insertin and tensin. However, the insertin-specific mRNA contributes
      relatively little to expression of insertin domains in cells. Insertin
      preparations from chicken gizzard contain mainly insertin domains formed from
      tensin by proteolysis.

PMID- 9556333
TI  - Occurrence of fibers and their association with talin in the cleavage furrow of
      PtK2 cells. Video supplement.

PMID- 9556334
TI  - Interactions of Listeria monocytogenes with infected host cells. Video
      supplement.

PMID- 9556335
TI  - Fertilization and pronuclear migration in the ctenophore, Beroe ovata. Video
      supplement.

PMID- 9556336
TI  - Measurement of traction forces in cells locomoting along a substratum. Video
      supplement.

PMID- 9556337
TI  - Computer modelling of the ciliary axoneme. Video supplement.

PMID- 9556338
TI  - Actin-based vesicle dynamics and exocytosis during wound wall formation. Video
      supplement.

PMID- 9556339
TI  - Three flagellar motilities in Chlamydomonas unrelated to flagellar beating. Video
      supplement.

PMID- 9556340
TI  - "Ethnicity, Aging, and Oral Health Outcomes: Findings from the ICS-II USA
      Research Locations".

PMID- 9556341
TI  - [Atlas of cranial and spinal MRI--magnetic resonance imaging in carbon monoxide
      poisoning and Parkinsonian syndrome].

PMID- 9556342
TI  - [Atlas of cranial and spinal MRI--fever, headache and behavioral disorders].

PMID- 9556343
TI  - Interdigitated solenoid model for compact chromatin fibers.

PMID- 9556344
TI  - The enhancement of enzymatic rate accelerations by Bronsted acid-base catalysis.

PMID- 9556345
TI  - Liposome-catalyzed unfolding of acetylcholinesterase from Bungarus fasciatus.
AB  - The kinetics of thermal inactivation of acetylcholinesterase from the venom of
      the snake, Bungarus fasciatus, were studied at 45-54 degrees C. An Arrhenius plot
      reveals an activation energy of 113 kcal/mol. The thermally denatured enzyme
      displays the spectroscopic characteristics of a partially unfolded 'molten
      globule' state. The rate of thermal denaturation is greatly enhanced in the
      presence of unilamellar vesicles of dimyristoylphosphatidylcholine, the energy
      barrier for the transition being lowered from 113 to 52 kcal/mol. In contrast to
      our findings for partially unfolded Torpedo californica acetylcholinesterase
      [Shin et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 2848-2852], the thermally
      denatured snake enzyme does not remain bound to the liposomes but is released
      after unfolding and subsequently aggregates. The liposomes thus serve as
      catalysts for unfolding of the snake enzyme, and its rate of unfolding in the
      presence of liposomes can be described by the Michaelis-Menten equation (Km = 8 x
      10(-7) M). The phospholipid vesicles display a catalytic turnover number of kcat
      approximately 4 min-1, assuming 15 binding sites per vesicle for the snake
      acetylcholinesterase.

PMID- 9556346
TI  - Step-scan time-resolved FTIR spectroscopy of cytochrome P-450cam carbon monoxide
      complex: a salt link involved in the ligand-rebinding process.
AB  - Step-scan time-resolved Fourier transform infrared spectroscopy with a time
      resolution of 5 micros was applied to the carbon monoxide complex of cytochrome P
      450cam (CYP101) to study the bimolecular ligand-rebinding process after flash
      photolysis. Spectral changes in the CO ligand stretch vibration band and in the
      protein amide I' band were monitored simultaneously. In substrate complexes
      having the camphor C-8, C-9, and C-10 methyl groups, rebinding of the ligand and
      the relaxation of the protein proceed at the same rate within experimental
      errors. For substrate complexes missing the methyl groups, the relaxation fo the
      protein tends to relax slightly faster than the CO ligand rebinding to the heme
      iron. compared to the (1R)-camphor and the camphane complex, the bimolecular
      rebinding rate constant for P-450 bound with substrates lacking the methyl groups
      are increased by a factor of 10-40. An unusual signal at about 1719 cm-1 was
      found in the difference spectrum of the photolyzed minus nonphotolyzed CO complex
      which has not ben reported for other heme proteins so far. This signal is
      strongly pronounced in wild-type P-450cam bound with (1R)-camphor or camphane and
      in the D251N mutant bound with (1R)-camphor. In contrast, substrate-free P-450
      and the norbornane and norcamphor complexes reveal only a very weak signal or a
      changed band shape. On the basis of the crystal structure data, we suggest that
      this signal originates from the rearrangement of the hydrogen-bonding pattern or
      the protonation state of the salt link between Asp297, Arg299, and the heme
      propionate group.

PMID- 9556347
TI  - Voltage clamp studies on S-layer-supported tetraether lipid membranes.
AB  - Isolated subunits from the cell surface proteins (S-layer) of Bacillus coagulans
      E38-66 have been recrystallized on a glycerol dialkyl nonitol tetraether lipid
      (GDNT)-monolayer and the electrophysical features of this biomimetic membrane
      have been investigated in comparison to unsupported GDNT-monolayers. The GDNT
      monolayer, spread on a Langmuir-Blodgett trough, was clamped with the tip of a
      glass patch pipette. In order to investigate the barrier function and potential
      to incorporate functional molecules, voltage-clamp examinations on plain and S
      layer-supported GDNT-monolayers were per-formed. Our results indicate the
      formation of a tight GDNT-monolayer sealing the tip of the glass pipette, and a
      decrease in conductance of the GDNT-monolayer upon recrystallization of the S
      layer protein. Thus, the S-layer protein, apparently, did not penetrate or
      rupture the lipid monolayer. The valinomycin-mediated increase in conductance was
      less pronounced for the S-layer-supported than for the plain GDNT-monolayer,
      indicating differences in the accessibility and/or in the fluidity of the lipid
      membranes. Furthermore. in contrast to plain GDNT-monolayers. S-layer supported
      GDNT-monolayers with high valinomycin-mediated conductance persisted over long,
      periods of time, indicating enhanced stability. These composite S-layer/lipid
      films may constitute a new tool for electrophysical and electrophysiological
      studies on membrane-associated and membrane-integrated biomolecules.

PMID- 9556348
TI  - Interaction of phospholipid vesicles with smooth metal-oxide surfaces.
AB  - The interaction of phospholipid vesicles with planar metal oxide supports has
      been previously reported as a means of preparing supported lipid bilayers, which
      are useful models of biological membranes. Nevertheless, extant evidence that
      bilayers are actually formed is rather circumstantial, and the necessary and
      sufficient conditions for their formation have never been delineated. Here, we
      tackle this problem by using smooth planar optical waveguides as the support.
      Analysis of the lightmode spectra of the waveguides, measured in situ during the
      deposition process, yields the mass of lipid deposited at the solid/liquid
      interface. By comparing the optogeometric parameters of the structures assembled
      from the vesicles with those of a lipid bilayer of known structure assembled
      using the Langmuir-Blodgett technique, we show that in many cases the vesicles
      remain intact and form a supported layer of vesicles rather than a bilayer, and
      often mixed structures (intact vesicles embedded in a bilayer partially covering
      the surface) occur. Careful analysis of the lipid deposition kinetics
      corroborates this result. We have also found that divalent cations dramatically
      promote attachment of mixed phosphatidylcholine/phosphatidylglycerol vesicles to
      form supported vesicle layers, and bilayer formation from pure
      phosphatidylcholine vesicles.

PMID- 9556349
TI  - Lipids in total extracts from Acholeplasma laidlawii A pack more closely than the
      individual lipids. Monolayers studied at the air-water interface.
AB  - Pressure-area curves were obtained at 25, 35 and 45 degrees C for total lipid
      extracts and four individual glucolipids isolated from Acholeplasma laidlawii
      strain A-EF22. The glucolipids are 1,2-diacyl-3-0-(alpha-D-glucopyranosyl)-sn
      glycerol (MGlcDAG), 1,2 -diacyl-3-0-[alpha-D-glucopyranosyl-(1-->2)-0-alpha-D
      glucopyranosyl] -sn-glycerol (DGlcDAG), 1,2-diacyl-3-0-[alpha-D-glucopyranosyl-(1
      ->2)-0-(6-0-acyl-alpha-D-gluco pyranosyl)]-sn-glycerol (MADGlcDAG), and 1,2
      diacyl-3-0-[glycerophosphoryl-6-0-(alpha-D-glucopyranosyl-(1-- >)-0-alpha-D
      glucopyranosyl)]-sn-glycerol (GPDGlcDAG). The total lipid extracts were obtained
      from A. laidlawii, grown at 37 degrees C with fatty acids of varying degrees of
      unsaturation and chain length. The mean surface area per molecule was obtained
      from these pressure-area curves at surface pressures equal to 10, 20, 30 and 40
      mN/m. It was found that the interfacial area of the lipids increases with
      increasing degree of unsaturation, but is nearly independent of the acyl chain
      length at constant unsaturation. The surface charge density varied between 4.7 x
      10(-3) e-/angstrom(2) and 9.4 x 10(-3) e-/angstrum(2) for the total lipid
      extracts studied, but did not exhibit any consistent dependence on variations in
      degree of unsaturation or acyl chain length. The mean area per molecule was found
      to be smaller for the total lipid extracts than for the individual lipids. It is
      concluded that the bacterium strives to regulate its lipid composition in such a
      way that the packing of the lipids in the membrane is appropriately tight, and/or
      to keep a slight negative spontaneous curvature of the lipid bilayer of the cell
      membrane ("optimal packing"). This is in accordance with the physico-chemical
      model for the regulation of the lipid composition in the membrane of A.
      laidlaiwii previously presented by us (see e.g. Andersson, A.-S., Riffors, L.,
      Bergqvist, M., Persson, S. and Lindblom, G. (1996) Biochemistry 35, 11119-11130).

PMID- 9556350
TI  - Insulin therapy of prediabetes suppresses TH1 associated gene expression in BB
      rat pancreas.
AB  - Subcutaneous insulin treatment of young diabetes prone BB rats has been shown
      previously to suppress the development of autoimmune diabetes. In this study the
      hypothesis was tested that exogenous insulin may deviate the autoimmune process
      by acting on the Th1/Th2 cytokine balance in the pancreas. BB rats were implanted
      with pellets which continuously released insulin, at 50 d of age. Three weeks
      later cytokine mRNA expression in the pancreas and insulitis score were
      determined. While in control BB rats high levels of IFNgamma mRNA were detectable
      by RT-PCR, insulin treatment almost completely suppressed IFNgamma mRNA levels
      without concomitant upregulation of counterregulatory IL-10 and TGFbeta gene
      expression. Insulin also suppressed gene expression of inducible nitric oxide
      synthase. Mean insulitis scores were decreased after insulin treatment. We
      conclude that the protective effects of insulin treatment may not be due to the
      induction of protective Th2 immune reactivity but to general downregulation of
      immune activation in the pancreas, and hence also of Th1 autoimmunity.

PMID- 9556351
TI  - The insulin gene region and susceptibility to insulin-dependent diabetes mellitus
      in four races; new insights from Afro-Caribbean race-specific haplotypes.
AB  - The IDDM2 component of the genetic susceptibility to insulin-dependent diabetes
      mellitus (IDDM) has been mapped to chromosome 11p15.5. The exact identity of
      IDDM2 remains uncertain. It has been suggested that IDDM2 maps within the 5' VNTR
      (variable number tandem repeat) polymorphism upstream of the insulin gene (INS).
      This has not been confirmed and a contribution from other INS gene region
      polymorphisms cannot be excluded. We present INS region genotype data from four
      racial groups: the Japanese, Hong Kong Chinese, North Indian Asians and Afro
      Caribbeans (two groups; one born and resident in the UK, one in Jamaica). These
      races have not been previously studied with the range of INS region polymorphisms
      included here. No INS polymorphism was associated with IDDM across all races.
      These data from this study thus do not identify any INS polymorphism as IDDM2.
      The Afro-Caribbean race showed a very different distribution of INS genotypes
      from the other races and novel race-specific INS haplotypes were identified.
      Analysis of these excluded a contribution to susceptibility to IDDM from the-
      23HphI INS polymorphism. An Afro-Caribbean INS haplotype which differed only at
      the VNTR from the very protective INS haplotype (VPH) identified in white
      Caucasians was detected. Population analysis of this haplotype will allow direct
      assessment of the role of the VNTR in susceptibility to IDDM. In conclusion, the
      diverse Afro-Caribbean TH/INS/IGF2 haplotypes identified in this study will be
      valuable in mapping IDDM2 more precisely.

PMID- 9556352
TI  - Primary biliary cirrhosis an epithelitis: evidence of abnormal salivary gland
      immunohistochemistry.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown
      etiology. Nearly 93% of patients with PBC exhibit evidence of focal
      sialoadenitis. In an earlier study, we reported evidence of aberrant expression
      of PDC-E2, or a mimeotope, in the salivary glands of patients with PBC that had
      Sjogren's syndrome. At the time of the previous study, data was not yet available
      regarding patients with PBC without sicca complaints. Therefore, to investigate
      the extent of salivary gland involvement in PBC, we collected lip biopsy sections
      from 9 PBC patients diagnosed as PBC by liver biopsy, without clinical or
      histologic features of Sjogren's syndrome and 9 PBC patients with established
      Sjogren's syndrome. Using immunohistochemical staining with both a murine
      monoclonal antibody. C355.1, and a human combinatorial antibody, SP4, we examined
      the ducts of these salivary glands for the presence of the characteristic
      aberrant staining pattern found in patients with PBC. We report that 6/9 PBC
      patients fulfilling established Sjogren's syndrome criteria and 6/9 PBC patients
      lacking features of Sjogren's syndrome showed intense staining of the ductal
      epithelial cells of the salivary gland. These data suggest that the PBC-specific
      antigen recognized by C355.1 and SP4 in bile duct epithelial cells is expressed
      aberrantly in the salivary gland in 66% of patients with PBC, independent of
      Sjogren's syndrome. This finding suggests a common disease process in these two
      tissues. Further, expression of this molecule may be an early marker of salivary
      gland involvement in patients with PBC.

PMID- 9556353
TI  - Heat shock proteins and arthritis--new readers start here.
AB  - The possible roles of heat shock proteins in the pathogenesis of inflammatory
      arthritis have been discussed for a number of years, and investigated intensively
      in both animal models and human disease. This review surveys evidence which has
      pointed, on the one hand, to hsp as targets of a pathogenic immune response, and
      on the other, to an immunoregulatory role for T cell recognition of self hsp. The
      extent to which findings in experimental animals have led to further insights
      applicable to human disease is also emphasised.

PMID- 9556354
TI  - Melatonin, immune modulation and aging.
AB  - Melatonin is a hormone secreted by the pineal gland in response to photoperiods
      and influences many important biological processes. For one, Melatonin has been
      shown to produce resistance to cancer and infectious diseases in aged animals.
      Studies in animals have demonstrated melatonin-related mechanisms of action on
      immunoregulation. Additionally, melatonin has been successfully used in humans,
      along with interleukin-2, as a treatment of solid tumors. In vivo and in vitro
      studies show melatonin enhances both natural and acquired immunity in animals.
      Despite all of this intriguing evidence, melatonin's mechanism of action on the
      immune system is only partially defined. It does, however, appear to act through
      lymphocyte receptors, and perhaps, receptors on other immune tissues, to modulate
      immune cells. In order to understand immunomodulation and anti-cancer effects,
      information on melatonin and it's interactions with other endocrine hormones are
      summarized.

PMID- 9556355
TI  - Locomotion and chemotaxis of lymphocytes.
AB  - The behaviour of locomotor T and B lymphocytes and the chemoattractants to which
      they respond in vitro are reviewed. Following activation, T cells respond by
      locomotion and chemotaxis to cytokine attractants including IL-15 and IL-2 and
      several chemokines. In activated B cells chemotaxis may be signalled through the
      antigen receptor. Conversely resting lymphocytes respond poorly to the above
      signals though their locomotion is activated by contact with high endothelial
      venular cells. These differences in locomotion between resting and activated
      lymphocytes, together with differences in adhesion, may explain why activated
      lymphocytes migrate preferentially into inflammatory sites while resting cells
      recirculate.

PMID- 9556356
TI  - Prevalence of islet cell antibodies (ICA) in diabetes mellitus and other diseases
      in Cubans.

PMID- 9556357
TI  - Glutamine as an activator of immune cells: how does it work?

PMID- 9556358
TI  - Workshop: Calcium and related nutrients. Washington, DC, July 9-10, 1996.

PMID- 9556359
TI  - Neuronal circuitry and synaptic connectivity of the basal ganglia.
AB  - The concept of organization of the basal ganglia has changed markedly over the
      last 10 years. These developments have led to the introduction of a schematic
      model of the functional circuitry of the basal ganglia that accounts for normal
      and abnormal basal ganglia functions. The recent introduction of powerful
      techniques for the analysis of neuronal networks has led to many new developments
      in our understanding of the anatomic and synaptic organization of the basal
      ganglia. The objective of this article is to go from the established model of the
      basal ganglia connectivity to new anatomic findings that lead to reconsideration
      and refinement of some aspects of the models.

PMID- 9556360
TI  - Adolescents. Abused teens.

PMID- 9556361
TI  - Nursing. Mixed signals.

PMID- 9556362
TI  - Satisfaction. Boomer bust.

PMID- 9556363
TI  - Religion. Faith in managed care.

PMID- 9556364
TI  - Kiddiecare isn't child's play.

PMID- 9556365
TI  - Construction. Shock absorber.

PMID- 9556366
TI  - Recent Progress of Pineal Research--40 Years After Discovery of Melatonin.
      Proceedings of the AsiaPacific Pineal Meeting. Hamamatsu, Japan, March 28-31,
      1997.

PMID- 9556367
TI  - Length growth in fission yeast: is growth exponential?--No.

PMID- 9556368
TI  - Perspectives on the Use of Interleukin-2 in Cancer Treatment. Proceedings of a
      conference. San Francisco, California, USA. July 10-13, 1997.

PMID- 9556369
TI  - Point-counterpoint. Mass population skin cancer screening is not worthwhile.

PMID- 9556370
TI  - Point-counterpoint. Mass population skin cancer screening can be worthwhile--(if
      it's done right)

PMID- 9556371
TI  - Melanoma in a patient with multiple unilateral vascular tumours.

PMID- 9556373
TI  - The depolarization response element in acetylcholine receptor genes is a dual
      function E box.

PMID- 9556372
TI  - Porous balloon catheters.

PMID- 9556374
TI  - Special issue: Complement and disease.

PMID- 9556375
TI  - Helpful tips for extralabel drug use: record keeping, record access, and product
      labels. The FDA-Center for Veterinary Medicine and the American Veterinary
      Medicine Association.

PMID- 9556376
TI  - Selected resources on pediatric pain.

PMID- 9556378
TI  - RP11 is the second most common locus for dominant retinitis pigmentosa.

PMID- 9556377
TI  - Homozygosity for Asn86Ser mutation in the CuZn-superoxide dismutase gene produces
      a severe clinical phenotype in a juvenile onset case of familial amyotrophic
      lateral sclerosis.

PMID- 9556379
TI  - Should dentists be obligated to report their HIV status?

PMID- 9556380
TI  - [Mechanisms of host defense and granulomatous inflammation in acid-fast bacilli
      infection].

PMID- 9556381
TI  - [Induction and function of Th1 cells as the effector cells in anti-tuberculosis
      immunity].

PMID- 9556382
TI  - [Role of gamma/delta cells in tuberculous infection].

PMID- 9556383
TI  - [Role of immune responses in tuberculosis].

PMID- 9556384
TI  - [Merit and demerit of cytokines in the prevention and treatment of tuberculosis].

PMID- 9556385
TI  - [Comment on A. Hohmann, W. Russmann, F.A. Kaszli: Quality of vision screening in
      childhood].

PMID- 9556386
TI  - Transmission of fungal spores in space and their conditions for survival: a
      review.
AB  - The transfer of fungal spores to suitable hosts or nutrient substrates frequently
      depends on spore discharge and aerial transport to transmit the species. Factors
      affecting spore translocation and travel have been evaluated mycologically and
      mathematically and are reviewed. Global disease spread and transmission
      monitoring are discussed.

PMID- 9556387
TI  - Plasmid patterns of Bacillus thuringiensis strains and isolates.
AB  - Bacillus thuringiensis produces crystal proteins which are toxic to several
      orders of economically important insects and other invertebrates. The genes
      encoding these toxins reside mainly on plasmids. This report consists of a
      comparative analysis of the plasmid content of a number of B. thuringiensis
      strains and isolates which may facilitate the search for novel toxin genes and
      other important products of this organism.

PMID- 9556388
TI  - Silhouette. Elena Lucrezia Cornaro Piscopia (1646-1684), the first university
      alumna in the world.

PMID- 9556389
TI  - 1997-1998 Neurobehavioral Teratology Society Membership List.

PMID- 9556390
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 13-1998. A 23-year-old man with progressive weakness and
      paresthesias.

PMID- 9556391
TI  - A dangerous error in the dilution of 25 percent albumin.

PMID- 9556392
TI  - Prophylactic use of implanted cardiac defibrillators in patients at high risk for
      ventricular arrhythmias after coronary-artery bypass graft surgery.

PMID- 9556393
TI  - Prophylactic use of implanted cardiac defibrillators in patients at high risk for
      ventricular arrhythmias after coronary-artery bypass graft surgery.

PMID- 9556394
TI  - Increased nuchal translucency and fetal chromosomal defects.

PMID- 9556395
TI  - Increased nuchal translucency and fetal chromosomal defects.

PMID- 9556396
TI  - Terminal sedation.

PMID- 9556397
TI  - Terminal sedation.

PMID- 9556398
TI  - Treatment of pain in dying patients.

PMID- 9556399
TI  - Lack of relation between culture and anorexia nervosa--results of an incidence
      study on Curacao.

PMID- 9556400
TI  - Social missions of academic health centers.

PMID- 9556401
TI  - Social missions of academic health centers.

PMID- 9556402
TI  - Unpaid expert witnesses.

PMID- 9556403
TI  - Unpaid expert witnesses.

PMID- 9556404
TI  - Unpaid expert witnesses.

PMID- 9556405
TI  - Sparganosis in non-human primates.

PMID- 9556406
TI  - The demonstration of candidal pseudohyphae in salivary smears as a method of
      early diagnosis of oral candidiasis in patients with acute myeloid leukemia.
AB  - To investigate the oral coloniation of candidal pseudohyphae, a salivary smear
      method was tested against the use of mucosal smears in 10 patients with acute
      myeloid leukemia. The salivary smears showed to be reproducible and more
      sensitive than mucosal smears for the demonstration of Candida organisms. The
      salivary smear method was applied to another group of 10 patients with acute
      myeloid leukemia during a 28-day period. According to swab cultures, 8 patients
      were colonized with Candida spp. on day 0, whereas 2 patients were unclonized on
      day 0, and remained so. All colonized patients developed acute oral candidiasis.
      According to the salivary smear method, 5 patients were colonized with
      pseudohyphae as early as on day 0, whereas 3 patients  became colonized with
      pseudohyphae within the first 7 days. Pseudohyphae were detected with a median of
      4 days prior to the emergence of acute oral candidiasis, and the detection of
      acute oral candidiasis was associated with an increase in the quantity of
      pseudohyphoae. The study suggests that the demonstration of candidal pseudohyphae
      in salivary smears is an early indicator of subsequent development of acute oral
      candidiasis. Further studies are neded to clairfy whether early treatment based
      on this finding will reduce the occurrence of acute oral candidiasis and
      disseminated candidiasis in these patients.

PMID- 9556408
TI  - No evidence-based medicine.

PMID- 9556407
TI  - Characterization of a 4.2-kb plasmid isolated from periodontopathic spirochetes.
AB  - Oral anaerobic treponemes are assoicated with active periodontal disease and may
      comprise up to 57% of the microbiota in periodontal pockets. Four treponeme
      strains (designated U2a, U2b, U9b, and U9c) isolated from clincial cases were
      found to harbor a new 4.2-kb plasmid when plasmid DNA was extracted and purified
      employing the Qiagen Plasmid Kit. This plasmid differs from the smaller plasmids
      (2.0-, 2.6-, and 2.7-Kb) reported previously by others in Treponema denticola.
      The newly discovered 4.2-kb plasmid was found to be the same in all four
      treponeme strains by restriction endonuclease analysis. It is a circular plasmid
      since restriction with PstI, Pvu II, Sma I, Xma I, Ava 1 or Bam HI produced a
      single band of the same size. Bacterial strain U2b was shown to be Treponema
      socranskii and U9c to be T. denticola. The plasmid is designated "pTS1". The
      presence of the same plasmid in different species of the treponemes isolated from
      the same patient suggests the possibility of a naturally occurring genetic
      transfer system within the oral spirochetes or their ability to take up and
      maintain mobilizable plasmids.

PMID- 9556409
TI  - Epidemiologic study of infants with biliary atresia.

PMID- 9556410
TI  - Alternative routes of drug administration--advantages and disadvantages (subject
      review)

PMID- 9556411
TI  - Urinary tract infection controversy and questions.

PMID- 9556413
TI  - Urinary tract infection controversy and questions.

PMID- 9556412
TI  - Urinary tract infection controversy and questions.

PMID- 9556414
TI  - Pediatric Residency Training in an Era of Managed Care. Proceedings of a National
      Conference. May 4, 1996.

PMID- 9556415
TI  - Alterations in fascin-expressing germinal center dendritic cells in neoplastic
      follicles of B-cell lymphomas.
AB  - Germinal center dendritic cells (GCDCs) have essential functions in retention of
      immune complexes within secondary follicles, B-lymphocyte antigenic stimulation,
      B-cell activation, homing of B-cells via adhesion molecules such as ICAM-1 and
      VCAM-1, and B-cell survival via apoptosis. The neoplastic cells of follicular
      lymphomas (FLs) are thought to derive from follicular B lymphocytes, but their
      relationship to GCDCs remains unclear. This study used immunohistochemical
      staining for fascin, a 55-kDa actin-bundling protein strongly expressed in GCDCs
      and their processes, to evaluate their distribution in neoplastic follicles.
      Forty-two cases of B-cell FL were evaluated, and immunoreactive staining for
      fascin was compared with six cases of Castleman's disease (CD) and six cases of
      follicular hyperplasia. FLs generally revealed decreased or absent fascin
      staining GCDCs, suggesting loss of fascin expression by dendritic cells in
      neoplastic follicles compared with hyperplastic follicular centers. In some
      follicles, there was partial retention of dendritic architecture with islands of
      residual syncytial network. Interdigitating reticulum cells in the parafollicular
      regions revealed normal fascin expression with intense staining of dendritic
      processes. In contrast with FLs, cases of follicular hyperplasia revealed normal
      or increased fascin-positive follicular dendritic cells, and in cases of hyaline
      vascular CD, follicular dendritic cells revealed tight syncytial networks. These
      results suggest that GCDCs are deficient in neoplastic follicles, compared with
      benign reactive or hyperplastic follicles. This alterations in the germinal
      center microenvironment might explain the inability of FL cells to present
      antigen to T lymphocytes and to mount an effective antitumor immune response.

PMID- 9556416
TI  - Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis.
AB  - We report here a case of fibrillary glomerulonephritis arising in a 43-year-old
      man with a polyclonal gammopathy, who presented with progressive renal
      insufficiency, microscopic hematuria, and mild proteinuria (0.7 g/d).
      Ultrastructural studies showed deposits of randomly oriented fibrils in the
      glomerular mesangium and adjacent portions of some glomerular basement membranes,
      with a mean fibril thickness of 14.3 nm, highly consistent with fibrillary
      glomerulonephritis. The Congo red stain was negative on histologic sections.
      Immunofluorescence studies revealed strong mesangial and focal glomerular
      capillary staining for immunoglobulin (Ig) G, complement (C) 3, and kappa light
      chains, with minimal staining for IgA, IgM, C1q, or lambda light chains. The IgG
      present was entirely of the IgG1 subclass. This case is quite unusual for
      fibrillary glomerulonephritis, which typically presents with polyclonal IgG
      deposits and IgG4 as the dominant IgG subclass present. Monoclonal deposits are
      more frequently associated with immunotactoid glomerulopathy, characterized
      ultrastructurally by microtubule-like structures 30 to 50 nmn thick, often in
      parallel arrays. The present case illustrates that although fibrillary
      glomerulonephritis and immunotactoid glomerulopathy might be distinguishable on
      ultrastructural grounds, there is overlap between these two entities with respect
      to the potential composition of the glomerular deposits present.

PMID- 9556417
TI  - Analysis of human papillomavirus infection and molecular alterations in
      adenocarcinoma of the cervix.
AB  - Although molecular alterations involved in the development of squamous cell
      carcinoma of the cervix have been extensively described, these genetic changes
      have not been as well characterized in the development of cervical
      adenocarcinoma. Twenty-seven paraffin-embedded adenocarcinomas of the cervix,
      including three cases of adenoma malignum, were analyzed for molecular
      alterations associated with other gynecologic malignancies. The presence of human
      papillomavirus (HPV) was assessed by polymerase chain reaction (PCR) using
      internally nested consensus primers. HPV types were identified by restriction
      endonuclease digestion of the PCR products, using DNA sequencing to confirm each
      digestion pattern. The presence of HPV was correlated with immunohistochemical
      expression of the p53 gene product, the presence of mutations in codon 12 of Ki
      ras, and allelic deletion of markers associated with the development of other
      gynecologic carcinomas. HPV was identified in 16 (59%) of 27 cases, including
      type 18 in 7 tumors, type 16 in 7 tumors, and type 45 in 2 tumors. HPV types 16
      and 45 were always identified in adjacent uninvolved cervical epithelium, but HPV
      type 18 was absent from the adjacent non-neoplastic epithelium in four of the
      seven positive cases. HPV was not identified in any of three cases of adenoma
      malignum. Diffuse immunohistochemical staining of the p53 gene product was
      present in only one (HPV-negative) tumor. A mutation in codon 12 of Ki-ras was
      observed in one endocervical adenocarcinoma (with an endometrioid pattern). Loss
      of heterozygosity was identified only for a marker on chromosome 6p in one
      mucinous endocervical carcinoma. Most endocervical adenocarcinomas lack molecular
      alterations characteristic of other histologically similar gynecologic
      malignancies, as well as those described in cervical squamous cell carcinomas.

PMID- 9556418
TI  - In situ hybridization with biotinylated tyramide amplification: detection of
      human papillomavirus DNA in cervical neoplastic lesions.
AB  - A novel peroxidase-mediated amplification system, which is based on the
      deposition of biotinylated tyramide (BT) molecules, was recently described for
      immunohistochemistry and in situ hybridization (ISH). We report here a highly
      sensitive ISH system combined with a microwave prehybridization treatment and BT
      enhancement after hybridization. Our ISH with BT amplification can detect human
      papillomavirus (HPV) 16 DNA signals in the fixed SiHa cell, suggesting the
      ability to detect single or few copies of HPV DNA. To confirm its diagnostic
      usefulness, we used our ISH with BT amplification to detect HPV 16 DNA in 81
      cases of cervical neoplastic lesions, which had been used for routine pathologic
      diagnosis. Of 81 tumors, 47 (58%) showed HPV 16 DNA, of which 29 and 18 were
      cervical intraepithelial neoplasia (CINs) and invasive cancers, respectively. In
      almost all of the invasive cancers positive for HPV 16 DNA, ISH revealed a basic
      dot signal pattern in the nuclei, suggesting that HPV DNA integrated into tumor
      cell DNA. On the other hand, low-grade CINs displayed a diffuse, mainly episomal,
      signal pattern, which decreased in frequency with increased grade of CIN. Our ISH
      with BT amplification is highly sensitive and can be used to detect various genes
      and their expressions.

PMID- 9556419
TI  - Erythropoietin immunolocalization in renal cell carcinoma.
AB  - Erythropoietin (EPO) is a well-recognized hormone that induces erythrocytosis in
      a wide range of physiologic and pathologic situations in mammals. One of these
      situations is a paraneoplastic erythrocytosis, which might be seen in association
      with various neoplasms, including renal cell carcinoma (RCC), hepatoma, and
      cerebellar hemangioblastoma. Although there have been multiple studies confirming
      the association between this erythrocytosis and the production of EPO by tumor
      cells, immunohistochemical detection of EPO in formalin-fixed, paraffin-embedded
      tissue was not described. We report on the use of microwave antigen retrieval to
      detect EPO in RCCs in such routinely processed tissues. We selected 19 RCCs
      received as nephrectomy specimens, fixed in formalin, and routinely processed.
      These cases were previously diagnosed on the basis of morphologic,
      immunohistochemical, and clinical features. We examined the immunoreactivity of
      these specimens with a monoclonal anti-EPO antibody. Fetal (20 wk gestational
      age) liver served as a positive control. Intense positive immunoreactivity was
      observed as cytoplasmic, granular staining in fetal hepatocytes. Fourteen RCCs
      (10 clear cell and 4 tubulopapillary types) demonstrated unequivocal cytoplasmic
      immunoreactivity. Additionally, two clear cell tumors were only focally positive,
      whereas three (16%) were negative. EPO immunoreactivity might thus prove to be of
      value in the diagnosis or confirmation of RCC, particularly in the context of
      routinely processed material.

PMID- 9556420
TI  - Cytomegalovirus infection in the colon of bone marrow transplantation patients.
AB  - The histologic distinction between cytomegalovirus (CMV) infection and graft
      versus-host disease (GVHD) in the colon in bone marrow transplantation (BMT)
      patients relies heavily on the identification of viral inclusions, because the
      morphologic features of these two diseases are otherwise similar. The aim of this
      study was to assess (1) the prevalence of colonic CMV infection in BMT patients
      with the use of DNA in situ hybridization (ISH); and (2) the sensitivity and
      specificity of light microscopy in establishing a diagnosis of CMV infection in
      the colon of these patients. Fifty-five colonic mucosal biopsy samples from 50
      consecutive allogeneic BMT patients with diarrhea were evaluated histologically
      for the presence of typical or atypical (suspicious, but not diagnostic) CMV
      inclusions and, if negative, for the grade of GVHD. CMV DNA ISH analysis was
      performed on all of the biopsy specimens and was correlated with the histologic
      and clinical findings. Histologic analysis revealed only one patient with
      morphologically typical CMV inclusions. Four other cases contained an isolated
      atypical mesenchymal cell with features considered suspicious, but not
      diagnostic, for CMV inclusions. All of these five cases exhibited histologic
      features that were otherwise indistinguishable from GVHD grades 1 to 2. The
      single case that was histologically positive for CMV was confirmed by DNA ISH. Of
      the four histologically atypical cases, only one was confirmed to be CMV positive
      by DNA ISH. Of the remaining 45 patients, 35 had GVHD, 1 had pseudomembranous
      colitis, 1 had ischemic colitis, and 8 had no abnormalities found. Light
      microscopic examination is a sensitive method of screening for CMV infection in
      the colon of BMT patients but is less specific than DNA ISH. CMV infection is an
      infrequent cause of colitis in our BMT population.

PMID- 9556421
TI  - Causes of death in autopsied liver transplantation patients.
AB  - Liver transplantation is an established treatment for multiple end-stage liver
      diseases, yet little information is available on the autopsy-determined causes of
      death in liver transplant recipients. We undertook a retrospective study of the
      immediate causes of death in all liver transplant recipients who underwent
      autopsy at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,
      from January 1982 to January 1997. Infections were the most frequent cause of
      death, present in 64% of a total of 321 cases. Overall, the infections were
      bacterial in 48% of the cases, fungal in 22%, and viral in 12%. The ratio of
      infectious to noninfectious causes of death did not change significantly during
      the 15-year study period, and the relative percentages of bacterial, fungal, and
      viral infections showed relatively little variation on a year-to-year basis. Two
      thirds of all infections occurred during the first 100 days post transplantation.
      A precipitous drop in the number of infections (and the number of deaths)
      occurred by Day 90. Other major causes of death included liver failure (12%),
      pulmonary failure (10%), multiple organ system (8%), and cardiovascular causes
      (6%). Infections were the most frequent cause of death in this study population,
      suggesting that improvement in the prevention and treatment of infections is an
      important way to improve survival of liver transplant recipients.

PMID- 9556422
TI  - Prostatic atrophy: an autopsy study of a histologic mimic of adenocarcinoma.
AB  - Prostatic atrophy (PA) is one of the most frequent mimics of prostatic
      adenocarcinoma. It occurs almost exclusively in the peripheral zone of the gland
      and gained importance with the increasing use of needle biopsies for the
      detection of prostatic carcinoma The etiopathogenesis is unknown, and there is
      controversy related to the potential of PA as a precancerous lesion. The
      frequency increases with age. Compressions caused by hyperplastic nodules,
      inflammation, hormones, nutritional deficiency, or systemic or local ischemia,
      are all possible factors in the pathogenesis of PA. The peripheral zone of the
      prostate was step-sectioned and totally embedded from the bodies of 100
      consecutively autopsied men more than 40 years of age. The fragments were
      microscopically studied for presence of PA, latent (histologic) carcinoma, high
      grade prostatic intraepithelial neoplasia, local arteriosclerosis, and
      prostatitis. The prostates were macroscopically examined for the presence of
      nodular prostatic hyperplasia. The autopsy reports provided information
      concerning the presence of generalized atherosclerosis and benign or malignant
      nephrosclerosis. PA was seen in 85 of the 100 prostates examined and
      histologically was subtyped into simple, hyperplastic, and sclerotic atrophy. In
      65 (76.47%) of 85 cases, the histologic subtypes were combined. In 33 (50.76%) of
      these 65 cases, the three subtypes were seen concomitantly, favoring the
      hypothesis that they represent a morphologic continuum of only one lesion.
      Fibrosis of the stroma may or may not be present in simple and hyperplastic
      atrophy. Hyperplastic atrophy associated with fibrosis of the stroma is the
      histologic subtype that most frequently mimics adenocarcinoma Sclerotic atrophy
      always presents fibrosis of the stroma. PA increases with age, and, in our study,
      ischemia caused by local intense arteriosclerosis seems to be a potential factor
      for its etiopathogenesis. Because there was no relation to latent (histologic)
      carcinoma or high-grade prostatic intraepithelial neoplasia, PA is probably not a
      premalignant lesion.

PMID- 9556424
TI  - bcl-1 translocations are frequent in the paraimmunoblastic variant of small
      lymphocytic lymphoma.
AB  - To evaluate the usefulness of polymerase chain reaction analysis of
      translocations involving the bcl-1 and bcl-2 genes in variants of CD5-positive B
      cell lymphomas, we analyzed four cases classified as the paraimmunoblastic
      variant of small lymphocytic lymphoma. This neoplasm, originally identified as an
      aggressive, diffuse, B-lineage lymphoma related to small lymphocytic lymphoma,
      can be confused with variants of mantle cell lymphoma (an immunophenotypically
      and morphologically similar neoplasm). No translocations involving bcl-2 and the
      immunoglobulin heavy chain gene were identified; two cases had translocations
      involving the bcl-1 and the immunoglobulin heavy chain genes. The frequency of
      finding this translocation suggests that these categories of neoplasms might be
      extremely difficult to distinguish or that a closer relationship between these
      neoplasms exists than was initially proposed.

PMID- 9556423
TI  - Hormone receptor immunoreactivity in hemangioblastomas and clear cell renal cell
      carcinomas.
AB  - Several primary central nervous system (CNS) neoplasms, including meningiomas,
      spinal cord ependymomas, and acoustic nerve schwannomas, express hormone
      receptors. In the present study, we investigated hormone receptor
      immunoreactivity in hemangioblastomas on the basis of recent reports of these
      tumors complicating pregnancy. We also evaluated cases of renal cell carcinoma
      (RCC) metastatic to the CNS, hypothesizing that estrogen receptor (ER),
      progesterone receptor (PR), or androgen receptor (AR) immunoreactivity might help
      to distinguish between these histologically similar neoplasms.
      Immunohistochemical analysis for ERs, PRs, and ARs was performed on paraffin
      embedded sections of 27 hemangioblastomas, 12 primary clear cell RCCs, and 5
      clear cell RCCs metastatic to the CNS. All of the hemangioblastomas demonstrated
      PR immunoreactivity, whereas 10 of 12 primary RCCs were negative. In addition,
      four of the five metastatic RCC were PR positive. All but one primary RCC were ER
      negative. AR immunoreactivity was seen in three hemangioblastomas, five primary
      RCCs, and one metastatic RCC. Although hormone receptor immunoreactivity was
      unable to distinguish between hemangioblastoma and clear cell RCC metastatic to
      the CNS, the identification of PR immunoreactivity in hemangioblastomas is a new
      finding that might have adjuvant therapy treatment implications.

PMID- 9556425
TI  - Plasma cell granuloma of the oral cavity: a report of two cases and review of the
      literature.
AB  - We report two rare cases of plasma cell granuloma arising in the extragingival
      oral cavity. These are tumorous proliferations composed predominantly of reactive
      plasma cells. Both patients presented with solitary mass lesions that were
      clinically suspicious for malignancy. One patient presented with a mass that grew
      slowly for 2 years and involved the lip; in the second patient, a mass developed
      in the buccal mucosa Histologically, both lesions were characterized by lobules
      of plasma cells separated by thick collagenous bands. A variable number of
      admixed lymphocytes and histiocytes was noted in both cases. In situ
      hybridization and immunostaining for kappa and lambda light chains revealed a
      polyclonal plasma cell population. In situ hybridization for Epstein-Barr virus
      failed to demonstrate evidence of viral expression in either case. Both patients
      are free of disease after 8-month and 12-month follow-ups. Although plasma cell
      granuloma in the oral cavity is rare, it is important to recognize this entity as
      a benign inflammatory lesion.

PMID- 9556426
TI  - Detection of the SYT-SSX chimeric RNA of synovial sarcoma in paraffin-embedded
      tissue and its application in problematic cases.
AB  - We report the development of a reverse-transcriptase polymerase chain reaction
      assay that detects (in paraffin-embedded, formalin-fixed tissue) the SYT
      SSXchimeric RNA transcript resulting from the t(X;18) of synovial sarcoma. The
      primers chosen detect both of the SSX1 and SSX2 partners, and the target sequence
      is small enough (87 base pairs) to be reliably detected in archival and variably
      processed consultation material. To demonstrate its usefulness, we applied it to
      14 problematic cases, including spindle cell tumors of the thoracic region, of
      the neck, and of subcutaneous tissue. For instance, we show that, depending on
      the location, synovial sarcoma can mimic malignant solitary fibrous tumor, the
      spindle epithelial tumor with thymus-like differentiation, or skin adnexal
      tumors. Molecular detection of the SYT-SSX chimeric RNA should allow the
      reclassification of difficult cases in which the morphologic features overlap
      different entities or in which tumor nosology is still evolving.

PMID- 9556427
TI  - A novel Alcian yellow-toluidine blue (Leung) stain for Helicobacter species:
      comparison with standard stains, a cost-effectiveness analysis, and supplemental
      utilities.
AB  - Helicobacter pylori (Hp) gastritis is a worldwide problem significantly
      associated with duodenal and gastric peptic ulcer disease, gastric carcinomas,
      and MALT-type lymphomas. A simple, rapid, reproducible, reliable, and inexpensive
      stain to detect the organism in gastric biopsy specimens is thus of great value.
      To assess the reliability and cost-effectiveness of a novel Alcian yellow
      toluidine blue (Leung) stain for Hp, we stained 60 endoscopic mucosal biopsy
      specimens from patients with Hp gastritis and measured time to detection of
      organism, Hp numbers (scale, 1-5), and technical costs. We also stained serial 5
      microm step sections of 17 of these cases with the Giemsa and modified Steiner
      (MS) methods, and similar measurements were made. Also, specimens from various
      normal gastrointestinal sites and metaplastic lesions, as well as four cases each
      of giardiasis and cryptosporidiosis, were stained with the Leung method. In the
      subset of 17 cases, the Leung stain enhanced detection time and compared
      favorably with the Giemsa method, though the MS method was somewhat superior. Hp
      scores were similar among all groups. Mean time to detection and Hp scores were
      similar in the larger (n = 60) group stained with hematoxylin and eosin and the
      Leung stain. Material costs and technologist's time for Giemsa stains, however,
      were greater than for the Leung stain, and technologist's time for MS was nearly
      fourfold that of the Leung stain. With the Leung method, mucus from all
      gastrointestinal sites and metaplastic lesions stained yellow, and this stain
      provided excellent contrast and morphologic definition in giardiasis and
      cryptosporidiosis. We suggest that the newly developed Alcian yellow-toluidine
      blue (Leung) histochemical stain is a good choice as the standard for routine Hp
      staining because it is the cheapest and easiest to prepare and because
      pathologists' detection with this stain compares favorably with detection times
      achieved with more traditional and established methods.

PMID- 9556428
TI  - The differential diagnosis of pagetoid cells in the epidermis.
AB  - In addition to Paget's disease, a heterogeneous group of processes with diverse
      histogeneses can give rise to intraepidermal pagetoid cells. These diseases share
      as their common denominator the presence of discrete non-Malpighian or abnormal
      Malpighian cells occurring singly or in nests within the epidermis. Either
      Pagetoid cells can represent the only histologic change, as in pagetoid squamous
      cell carcinoma in situ or superficial spreading malignant melanoma in situ, or
      they can be an expression of an associated dermal or internal malignancy, as in
      sebaceous carcinoma or breast carcinoma. The histologic appearance of the
      pagetoid cells in these diverse disorders can be quite similar, rendering the
      differential diagnosis difficult. A review of the entities that enter into the
      differential diagnosis of intraepidermal pagetoid cells is presented, emphasizing
      their distinguishing histologic and immunophenotypic features and differential
      diagnosis.

PMID- 9556429
TI  - Extranodal multicentric Castleman's disease with cutaneous involvement.
AB  - Castleman's disease (CAD) is an unusual lymphoid hyperplasia that might be
      induced by an immunologic reaction to a virus or another infectious organism or
      drug. CAD commonly occurs in the mediastinal lymph nodes and less frequently in
      the neck lymph nodes, but other lymph nodes might be involved. Extranodal CAD is
      rare. We present a 72-year-old woman with diffuse 2- to 5-cm cutaneous nodules
      that had appeared a few months earlier. The patient underwent a biopsy, and the
      lesions resolved within 4 months. The patient was asymptomatic except for mild
      joint pains. Histopathologic findings showed a circumscribed nodule composed of
      lymphoid follicles with contracted germinal centers and expanded mantle zones.
      The lymphoid follicles were separated by perivascular bands of sclerotic
      collagen. Aggregates of epithelioid and dendritic histiocytes were present
      between follicles, with a prominent lymphoplasmacytic infiltrate and vascular
      proliferation. Although extranodal CAD has been reported in the skin, we think
      that this is the first reported case of multicentric cutaneous CAD without
      evidence of lymph node involvement.

PMID- 9556430
TI  - Post-transplantation lymphoproliferative disorder of donor origin in a sex
      mismatched renal allograft as proven by chromosome in situ hybridization.
AB  - We report a case of post-transplantation B-cell lymphoproliferative disorder
      (PTLPD) associated with Epstein-Barr virus (EBV) that developed in a renal
      allograft 5 months after transplantation. The lesion had a histologic appearance
      of diffuse large B-cell lymphoma with monoclonality demonstrated by in situ
      hybridization (ISH) for kappa and lambda mRNA. Both the male donor and the female
      recipient were EBV seropositive. The lymphoid cells in this lesion was proven to
      be of donor origin by ISH for the human Y chromosome on the paraffin-embedded
      sections of the allograft. The recipient of the other kidney from the same donor
      did not have evidence of lymphoma, and the patient was also free from disease 2
      years after surgical removal of the lymphoma This case is an unusual PTLPD of
      donor origin; the majority of such lesions in solid organ transplantations are of
      recipient origin. Our findings demonstrate that the origin of PTLPD can be
      documented in selected cases using ISH with probes to the Y chromosome.

PMID- 9556431
TI  - ATP-dependent uptake of natural product cytotoxic drugs by membrane vesicles
      establishes MRP as a broad specificity transporter.

PMID- 9556432
TI  - Computer system validation: an overview of official requirements and standards.
AB  - A brief overview of the relevant documents for companies in the pharmaceutical
      industry, which are to be taken into consideration to fulfil computer system
      validation requirements, is presented. We concentrate on official requirements
      and valid standards in the USA, European Community and Switzerland. There are
      basically three GMP-guidelines. their interpretations by the associations of
      interests like APV and PDA as well as the GAMP Suppliers Guide. However, the
      three GMP-guidelines imply the same philosophy about computer system validation.
      They describe more a what-to-do approach for validation, whereas the GAMP
      Suppliers Guide describes a how-to-do validation. Nevertheless, they do not
      contain major discrepancies.

PMID- 9556433
TI  - Software assessment under consideration of validation aspects: PPS and PMS
      systems.
AB  - Due to safety aspects, business risks and regulations of the FDA [FDA, 1983,
      Guide to Inspection of Computerized Systems in Drug Processing. USA] and the EU
      [EU-Leitfaden einer Guten Herstellpraxis for Arzneimittel, 1989, III/2244/87 Rev.
      3. Jan. 1989], computer based systems used in the pharmaceutical production have
      to be validated. In this paper we assessed which modules of production planning
      and control (PPS) and production management systems (PMS) have to be validated
      using a risk analysis procedure. It could be shown that the necessity of the
      validation concerns, above all, the modules of production management systems.
      Furthermore, a software supplier questionnaire was developed according to the V
      model of Royce [National Computing Centre, 1989. STARTS Publications, UK.]. The
      software supplier questionnaire was applied on four software products, which are
      mostly used in the pharmaceutical industry. Although these were developed
      according to a life cycle concept they fulfil the validation requirements,
      measured with the developed questionnaire, to a different degree. Especially the
      key element of the risk analysis was differently interpreted.

PMID- 9556434
TI  - Validation of the process control system of an automated large scale
      manufacturing plant.
AB  - The validation procedure for the process control system of a plant for the large
      scale production of human albumin from plasma fractions is described. A
      validation master plan is developed, defining the system and elements to be
      validated, the interfaces with other systems with the validation limits, a
      general validation concept and supporting documentation. Based on this master
      plan, the validation protocols are developed. For the validation, the system is
      subdivided into a field level, which is the equipment part, and an automation
      level. The automation level is further subdivided into sections according to the
      different software modules. Based on a risk categorization of the modules, the
      qualification activities are defined. The test scripts for the different
      qualification levels (installation, operational and performance qualification)
      are developed according to a previously performed risk analysis.

PMID- 9556435
TI  - Validation of computer systems: practical testing of a standard LIMS.
AB  - In recent years the introduction of computer systems for data handling in the
      pharmaceutical industry has increased. A standard LIMS (laboratory information
      management system) is software commercially available from different suppliers
      not only to facilitate data handling in laboratories but also to cover GMP
      requirements. Computer systems introduced in GMP-areas of pharmaceutical
      companies have to be validated. For a standard LIMS, the general validation of
      the program is performed by the supplier. Nevertheless, the user is always
      required to cover all phases of a validation. The objective of this paper is to
      discuss suitable test procedures for the most critical functions of a standard
      LIMS needed during the verification step of the validation process.

PMID- 9556436
TI  - Validation of a customized LIMS.
AB  - The advantages of customized Laboratory Information Management's Systems (LIMS)
      are their focus on the special aspects of their users' needs. Differences in the
      research and development or production chain in the individual organizations lead
      to an increase of interest in customized systems. Usually, also for customized
      systems, the core software is commercially available. The individual application
      modules as the Customized part of the LIMS are the most critical elements within
      the validation process. The topic of this paper is to give an example of the
      validation of a customized analytical LIMS. Validation of complex computerized
      systems guarantees the intended use and is therefore an unavoidable requirement
      of authorities. The audit of the supplier of the individual programmed modules,
      the user requirement specifications and the acceptance testing and results,
      respectively, on the software are of special interest within a customized LIMS.
      The hardware suitability and the principal processing routines are also a very
      important part of the whole validation process, but they will not be discussed in
      detail in this paper.

PMID- 9556437
TI  - Influence of Petasites hybridus on dopamine-D2 and histamine-H1 receptors.

PMID- 9556438
TI  - Effects of extracts and of individual components from Petasites on prostaglandin
      synthesis in cultured skin fibroblasts and on leucotriene synthesis in isolated
      human peripheral leucocytes.

PMID- 9556439
TI  - Study on clinical properties and mechanisms of action of Petasites in bronchial
      asthma and chronic obstructive bronchitis.

PMID- 9556440
TI  - Seasonal variation of the essential oil, valerenic acid and derivatives, and
      velopotriates in Valeriana officinalis roots and rhizomes, and the selection of
      plants suitable for phytomedicines.
AB  - During the seasons 1989-1993, Valeriana officinalis plants were investigated for
      their contents of essential oil, valerenic acid and derivatives, and
      valepotriates. Harvesting of the subterranean parts was started in August of the
      year in which the seeds were sown, and continued until the last week of April of
      the subsequent year. Despite marked variations from year to year, the maximum
      contents of essential oil in the subterranean parts of V. officinalis were found
      in September, ranging from 1.2% to 2.1% (v/w) based on dry weight (DW). Over the
      vegetation periods investigated, the composition of the oil remained more or less
      constant. Valerenic acid and its derivatives, and the valepotriates reached their
      maxima in February-March, with contents of 0.7-0.9% (DW) and 1.1-1.4% (DW),
      respectively. During the period 1989 - 1993, five V. officinalis strains were
      investigated for their contents of essential oil, valerenic acid and derivatives,
      and valepotriates in order to select plants suitable for phytomedicines. The
      selection procedures described in this paper finally yielded plant material (in
      1993) with a satisfactory content of essential oil (0.9%) combined with a high
      content of valerenic acid and derivatives (0.5%) which can be harvested in
      September of the year of sowing.

PMID- 9556441
TI  - The dose-response model for dioxin.

PMID- 9556442
TI  - Uncertainty and variability analysis in multiplicative risk models.
AB  - Currently, there is a trend away from the use of single (often conservative)
      estimates of risk to summarize the results of risk analyses in favor of
      stochastic methods which provide a more complete characterization of risk. The
      use of such stochastic methods leads to a distribution of possible values of
      risk, taking into account both uncertainty and variability in all of the factors
      affecting risk. In this article, we propose a general framework for the analysis
      of uncertainty and variability for use in the commonly encountered case of
      multireplicative risk models, in which risk may be expressed as a product of two
      or more risk factors. Our analytical methods facilitate the evaluation of overall
      uncertainty and variability in risk assessment, as well as the contributions of
      individual risk factors to both uncertainty and variability which is cumbersome
      using Monte Carlo methods. The use of these methods is illustrated in the
      analysis of potential cancer risks due to the ingestion of radon in drinking
      water.

PMID- 9556443
TI  - On construction of a dermal soil adherence PDF: response to Finley and Scott.

PMID- 9556444
TI  - [The current situation in the offering of medico-dental care benefits in
      Switzerland].

PMID- 9556445
TI  - [Mouth mucosal diseases. The continuing education course Stomatology Today in
      Bern of 11 November 1997].

PMID- 9556446
TI  - [Unfair competition].

PMID- 9556447
TI  - New hunt for the roots of resistance.

PMID- 9556448
TI  - Did life begin in hot water?

PMID- 9556449
TI  - France's sequencers aim to join the big league.

PMID- 9556450
TI  - Death by dozens of cuts.

PMID- 9556451
TI  - Transferred gene helps plants weather cold snaps.

PMID- 9556452
TI  - Magnetic brain imaging traces a stairway to memory.

PMID- 9556453
TI  - The vision of the pore.

PMID- 9556454
TI  - Memory and awareness.

PMID- 9556455
TI  - [Shoulder and elbow--a young specialty in surgery. Interview by Christiane
      Weseloh].

PMID- 9556457
TI  - Doctors as public speakers.

PMID- 9556456
TI  - International Clearinghouse for Birth Defects Monitoring Systems. Proceedings of
      the 24th annual meeting. Cape Town, South Africa, 19 November 1997. Abstracts.

PMID- 9556458
TI  - Proceedings of the European Union International Symposium on Ticks and Tick-Borne
      Diseases. Xi'An, People's Republic of China, September 2-6, 1996.

PMID- 9556459
TI  - European Gastro Club 29th conference. Munster, 3-4 October 1997. Abstracts.

PMID- 9556460
TI  - Breakfast, Cognition, and School Learning. Proceedings of a symposium. Napa,
      California, USA. August 28-30, 1995.

PMID- 9556461
TI  - De novo mtDNA nt 8993 (T-->G) mutation resulting in Leigh syndrome.

PMID- 9556462
TI  - Clinical interpretation of "Maternal endocrine activation during pregnancy alters
      neurobehavioral state in primate infants".

PMID- 9556463
TI  - Postmenopausal hormone use and risk for colorectal cancer and adenoma.
AB  - BACKGROUND: Accumulating evidence suggests that postmenopausal hormone use may
      decrease the risk for colorectal cancer. OBJECTIVE: To examine the relation of
      postmenopausal hormone therapy to colorectal adenoma and cancer. DESIGN:
      Prospective cohort and nested case-control studies. SETTING: Nurses' Health
      Study, a study of registered nurses recruited from 11 U.S. states. PARTICIPANTS:
      59 002 postmenopausal participants in the Nurses' Health Study. MEASUREMENTS:
      Self-reported data on hormone use and cases of distal colorectal adenoma and
      colorectal cancer obtained from biennial questionnaires completed from 1980 to
      1994. Cases of colorectal adenoma and cancer were confirmed by medical record
      review. RESULTS: 470 women developed colorectal cancer, and 838 developed distal
      colorectal adenomas. Current use of postmenopausal hormones was associated with a
      decreased risk for colorectal cancer (relative risk [RR], 0.65 [95% CI, 0.50 to
      0.83]). This association was attenuated in past users (RR, 0.84 [CI, 0.67 to
      1.05]) and disappeared 5 years after hormone use was discontinued (RR, 0.92 [CI,
      0.70 to 1.21]). Longer duration of current use did not afford greater protection
      (RR with > or =5 years of use, 0.72 [CI, 0.53 to 0.96]). Even after exclusion of
      women who reported having screening sigmoidoscopy, the relative risk for
      colorectal cancer seen with current hormone use was 0.64 (CI, 0.49 to 0.82). This
      suggests that the apparent protection is unlikely to be due to more intensive
      screening among hormone users. Current users also had a lower risk for large (>
      or =1 cm) adenomas than did women who had never used hormones (RR, 0.74 [CI, 0.55
      to 0.99]), although no overall material association was seen between colorectal
      adenoma and current hormone use (RR, 0.91 [CI,0.77 to 1.08]). CONCLUSIONS: The
      risk for colorectal cancer was decreased among women currently receiving
      postmenopausal hormone therapy, but the apparent reduction substantially
      diminished upon cessation of therapy. Hormone use was inversely associated with
      large colorectal adenomas but not small ones.

PMID- 9556464
TI  - Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians'
      Health Study.
AB  - BACKGROUND: In contrast to most observational studies, the randomized Physicians'
      Health Study found no association between aspirin use and colorectal cancer after
      5 years. OBJECTIVE: To determine the effect of randomly assigned aspirin
      treatment and self-selected aspirin use on the incidence of colorectal cancer
      after 12 years and to identify factors influencing the self-selection of regular
      aspirin use. DESIGN: Randomized clinical trial and prospective cohort study.
      SETTING: Male physicians throughout the United States. PATIENTS: 22071 healthy
      male physicians who were 40 to 84 years of age in 1982. INTERVENTION: 325 mg of
      aspirin every other day. In 1988, the aspirin arm of the randomized trial was
      stopped early. Participants then chose to receive either aspirin or placebo for
      the rest of the study. MEASUREMENTS: Annual questionnaires asking about aspirin
      use and other variables, including occurrence of cancer. RESULTS: Colorectal
      cancer was diagnosed in 341 patients during the study period. Over 12 years of
      follow-up, random assignment to aspirin was associated with a relative risk for
      colorectal cancer of 1.03 (95% CI, 0.83 to 1.28). Various gastrointestinal
      symptoms and diagnoses were strong predictors of less frequent aspirin use in
      1988. The relative risk for colorectal cancer in persons who used aspirin
      frequently after 1988 was 1.07 (CI, 0.75 to 1.53). CONCLUSIONS: In the
      Physicians' Health Study, both randomized and observational analyses indicate
      that there is no association between the use of aspirin and the incidence of
      colorectal cancer. The low dose of aspirin used and the short treatment period
      may account for the null findings. However, other characteristics associated with
      the use of aspirin in observational studies remain a plausible alternative
      explanation.

PMID- 9556465
TI  - Noninvasive mechanical ventilation in the weaning of patients with respiratory
      failure due to chronic obstructive pulmonary disease. A randomized, controlled
      trial.
AB  - BACKGROUND: In patients with acute exacerbations of chronic obstructive pulmonary
      disease, mechanical ventilation is often needed. The rate of weaning failure is
      high in these patients, and prolonged mechanical ventilation increases intubation
      associated complications. OBJECTIVE: To determine whether noninvasive ventilation
      improves the outcome of weaning from invasive mechanical ventilation. DESIGN:
      Multicenter, randomized trial. SETTING: Three respiratory intensive care units.
      PATIENTS: Intubated patients with chronic obstructive pulmonary disease and acute
      hypercapnic respiratory failure. INTERVENTION: A T-piece weaning trial was
      attempted 48 hours after intubation. If this failed, two methods of weaning were
      compared: 1) extubation and application of noninvasive pressure support
      ventilation by face mask and 2) invasive pressure support ventilation by an
      endotracheal tube. MEASUREMENTS: Arterial blood gases, duration of mechanical
      ventilation, time in the intensive care unit, occurrence of nosocomial pneumonia,
      and survival at 60 days. RESULTS: At admission, all patients had severe
      hypercapnic respiratory failure (mean pH, 7.18+/-0.06; mean PaCO2, 94.2+/-24.2 mm
      Hg), sensory impairment, and similar clinical characteristics. At 60 days, 22 of
      25 patients (88%) who were ventilated noninvasively were successfully weaned
      compared with 17 of 25 patients (68%) who were ventilated invasively. The mean
      duration of mechanical ventilation was 16.6+/-11.8 days for the invasive
      ventilation group and 10.2+/-6.8 days for the noninvasive ventilation group (P =
      0.021). Among patients who received noninvasive ventilation, the probability of
      survival and weaning during ventilation was higher (P = 0.002) and time in the
      intensive care unit was shorter (15.1+/-5.4 days compared with 24.0+/-13.7 days
      for patients who received invasive ventilation; P = 0.005). Survival rates at 60
      days differed (92% for patients who received noninvasive ventilation and 72% for
      patients who received invasive ventilation; P = 0.009). None of the patients
      weaned noninvasively developed nosocomial pneumonia, whereas 7 patients weaned
      invasively did. CONCLUSIONS: Noninvasive pressure support ventilation during
      weaning reduces weaning time, shortens the time in the intensive care unit,
      decreases the incidence of nosocomial pneumonia, and improves 60-day survival
      rates.

PMID- 9556466
TI  - Mammography use helps to explain differences in breast cancer stage at diagnosis
      between older black and white women.
AB  - BACKGROUND: Older black women are less likely to undergo mammography and are more
      often given a diagnosis of advanced-stage breast cancer than older white women.
      OBJECTIVE: To investigate the extent to which previous mammography explains
      observed differences in cancer stage at diagnosis between older black and white
      women with breast cancer. DESIGN: Retrospective cohort study using the Linked
      Medicare-Tumor Registry Database. SETTING: Population-based data from three
      geographic areas of the United States included in the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) program (Connecticut;
      metropolitan Atlanta, Georgia; and Seattle-Puget Sound, Washington).
      PARTICIPANTS: Black and white women 67 years of age and older in whom breast
      cancer was diagnosed between 1987 and 1989. MEASUREMENTS: Medicare claims were
      used to classify women according to mammography use in the 2 years before
      diagnosis as nonusers (no previous mammography), regular users (> or =2
      mammographies done at least 10 months apart), or peri-diagnosis users
      (mammography done only within 3 months before diagnosis). Information on
      mammography use was linked with SEER data to determine cancer stage at diagnosis.
      Stage was classified as early (in situ or local) or late (regional or distant).
      RESULTS: Black women were more likely to not undergo mammography (odds ratio
      [OR], 3.00 [95% CI, 2.41 to 3.75]) and to be given a diagnosis of late-stage
      disease (OR, 2.49 [CI, 1.59 to 3.92]) than white women. When women were
      stratified by previous mammography use, the black-white difference in cancer
      stage occurred only among nonusers (adjusted OR, 2.54 [CI, 1.37 to 4.71]). Among
      regular users, cancer was diagnosed in black and white women at similar stages
      (adjusted OR, 1.34 [CI, 0.40 to 4.51]). In logistic modeling, previous
      mammography alone explained about 30% of the excess late-stage disease in black
      women. In a separate model, previous mammography explained 12% of the excess late
      stage disease among black women after adjustment for sociodemographic and
      comorbidity information. CONCLUSION: Differences in breast cancer stage at
      diagnosis between older black and white women are related to previous mammography
      use. Increased regular use of mammography may result in a shift toward earlier
      stage disease at diagnosis and narrow the observed differences in stage at
      diagnosis between older black and white women.

PMID- 9556467
TI  - Incidence of idiopathic deep venous thrombosis and secondary thromboembolism
      among ethnic groups in California.
AB  - BACKGROUND: Few studies have compared the incidence of deep venous thrombosis
      among ethnic groups. OBJECTIVE: To determine the incidence of deep venous
      thrombosis among ethnic groups. DESIGN: Analysis of the linked California Patient
      Discharge Data Set from 1991 to 1994. SETTING: California. PATIENTS: 17991
      patients with idiopathic deep venous thrombosis (thrombosis without cancer or
      hospitalization within preceding 6 months) and 5573 patients with secondary
      thromboembolism (thromboembolism occurring within 3 months of seven different
      events). MEASUREMENTS: Ethnicity was determined by using race as documented in
      the data set. For idiopathic deep venous thrombosis, standardized age- and sex
      adjusted incidences were calculated. For secondary thromboembolism, proportional
      hazards modeling was done. RESULTS: The annual incidence of idiopathic deep
      venous thrombosis per 1000000 persons older than 18 years of age was 230 for
      white persons, 293 for African Americans (rate ratio, 1.27 [95% CI, 1.07 to
      1.51]), 139 for Hispanic persons (rate ratio, 0.60 [CI, 0.54 to 0.67]), and 60
      for Asians and Pacific Islanders (rate ratio, 0.26 [CI, 0.22 to 0.30]). Compared
      with white persons, Asians and Pacific Islanders who developed secondary
      thromboembolism had a significantly lower relative risk (range, 0.22 to 0.61) for
      all seven conditions analyzed. CONCLUSIONS: Compared with white persons, Asians
      and Pacific Islanders have a very low incidence of idiopathic deep venous
      thrombosis and a very low relative risk for secondary venous thromboembolism.

PMID- 9556468
TI  - Can degenerative aortic valve stenosis be related to persistent Chlamydia
      pneumoniae infection?
AB  - BACKGROUND: The cause of age-related degenerative (tricuspid) aortic valve
      calcification is largely unknown, but one typical characteristic is an active
      inflammatory process. The presence of Chlamydia pneumoniae in aortic valve
      stenosis was recently shown. OBJECTIVE: To test the hypothesis that if persistent
      C. pneumoniae infection plays an active role in the development of aortic
      stenosis, the organism can be detected in the healthy aortic valves of young
      persons. DESIGN: A cadaver study. SETTING: Oulu University Hospital, Oulu,
      Finland. SUBJECTS: 46 consecutive cadavers undergoing autopsy. MEASUREMENTS:
      Macroscopic and histologic pathology of aortic valves was determined. The
      presence of C. pneumoniae was determined by immunohistochemistry. RESULTS: 34 of
      46 valves were macroscopically normal. Early lesions of aortic valve disease were
      found in 12 valves (no lesions in valves from persons 20 to 40 years of age [n =
      15], 4 lesions in valves from persons 41 to 60 years of age [n = 16], and 8
      lesions in valves from persons older than 60 years of age [n = 15]; P = 0.004).
      Fifteen of 34 normal valves (44%) and 10 of 12 valves with early lesions (83%)
      had positive results on staining for C. pneumoniae (P = 0.02). In persons older
      than 60 years of age, the chance of an early lesion was higher if the valve
      tested positive for C. pneumoniae (7 of 8 valves with C. pneumoniae infection
      compared with 1 of 7 valves without C. pneumoniae infection; P = 0.01).
      CONCLUSIONS: Chlamydia pneumoniae is frequently present in aortic valves and is
      associated with early lesions of aortic valve stenosis in elderly persons.

PMID- 9556469
TI  - The Eisenmenger syndrome in adults.
AB  - For this article, the literature on the pathophysiology, clinical features,
      natural history, prognosis, and management of the Eisenmenger syndrome in adults
      was reviewed. English-language articles from 1966 to the present were identified
      through a search of the MEDLINE database by using the terms Eisenmenger,
      congenital heart disease, and pulmonary hypertension. Selected cross-referenced
      articles were also included. Articles on the pathophysiology, clinical
      presentation, evaluation, natural history, complications, and treatment of the
      Eisenmenger syndrome in adults were selected, and descriptive and analytical data
      relevant to the practicing physician were manually extracted. The Eisenmenger
      syndrome is characterized by elevated pulmonary vascular resistance and right-to
      left shunting of blood through a systemic-to-pulmonary circulation connection.
      Most patients with the syndrome survive for 20 to 30 years. The hemostatic
      changes associated with the syndrome may lead to thromboembolic events,
      cerebrovascular complications, or the hyperviscosity syndrome. Erythrocytosis is
      present in most patients, but excessive phlebotomy may cause microcytosis and
      exacerbate the symptoms of hyperviscosity. Other complications associated with
      the Eisenmenger syndrome include hemoptysis, gout, cholelithiasis, hypertrophic
      osteoarthropathy, and decreased renal function. Pregnancy or noncardiac surgery
      is associated with a high mortality rate in patients with the Eisenmenger
      syndrome. Because most pediatric patients with the Eisenmenger syndrome survive
      to adulthood, primary care physicians should have a thorough understanding of the
      syndrome; its associated complications; and medical and surgical management,
      especially with regard to the appropriate timing of phlebotomy and lung or heart
      lung transplantation. In addition, patients with the syndrome should undergo
      routine follow-up at a tertiary care center that has physicians and nurses with
      special expertise in congenital heart disease. In patients with the Eisenmenger
      syndrome who are pregnant or require noncardiac surgery, a multidisciplinary
      approach should be used to reduce the excessive mortality associated with these
      conditions.

PMID- 9556470
TI  - Have we treated AIDS too well? Rationing and the future of AIDS exceptionalism.
AB  - During the past decade, medical therapy for AIDS has become more effective but
      also prohibitively expensive. A medical tragedy has been transformed into a
      financial crisis, and society has responded by establishing special programs and
      sources of funding for AIDS. These maneuvers parallel earlier approaches to HIV
      testing and reporting that have collectively come to be known as
      'exceptionalism.' This paper suggests that exceptionalism in resource allocation
      is a fragile, short-term solution. In the long run, AIDS exceptionalism will
      create growing injustice and should be avoided. However, we should not eliminate
      the advances that this exceptionalism has already achieved. Instead, we need a
      working dialogue between these advances and public policy.

PMID- 9556472
TI  - Heparin prophylaxis for medical patients?

PMID- 9556471
TI  - A decision analysis of mandatory compared with voluntary HIV testing in pregnant
      women.
AB  - BACKGROUND: The benefit of antiretroviral therapy in reducing maternal-fetal
      transmission of HIV during pregnancy has caused a public policy debate about the
      relative benefits of mandatory HIV screening and voluntary HIV screening in
      pregnant women. OBJECTIVE: To evaluate the benefits and risks of mandatory
      compared with voluntary HIV testing of pregnant women to help guide research and
      policy. DESIGN: A decision analysis that incorporated the following variables:
      acceptance and benefit of prenatal care, acceptance and benefit of zidovudine
      therapy in HIV-infected women, prevalence of HIV infection, and mandatory
      compared with voluntary HIV testing. MEASUREMENTS: The threshold deterrence rate
      (defined as the percentage of women who, if deterred from seeking prenatal care
      because of a mandatory HIV testing policy, would offset the benefit of zidovudine
      in reducing vertical HIV transmission) and the difference between a policy of
      mandatory testing and a policy of voluntary testing in the absolute number of HIV
      infected infants or dead infants. RESULTS: Voluntary HIV testing was preferred
      over a broad range of values in the model. At baseline, the threshold deterrence
      rate was 0.4%. At a deterrence rate of 0.5%, the number of infants (n = 167)
      spared HIV infection annually in the United States under a mandatory HIV testing
      policy would be lower than the number of perinatal deaths (n = 189) caused by
      lack of prenatal care. CONCLUSIONS: The most important variables in the model
      were voluntary HIV testing, the deterrence rate associated with mandatory testing
      compared with voluntary testing, and the prevalence of HIV infection in women of
      child-bearing age. At high levels of acceptance of voluntary HIV testing, the
      benefits of a policy of mandatory testing are minimal and may create the
      potential harms of avoiding prenatal care to avoid mandatory testing.

PMID- 9556473
TI  - Cancer prevention: better late than never?

PMID- 9556474
TI  - Ethnic differences in mammography use among older women: overcoming the barriers.

PMID- 9556475
TI  - The Gram stain.

PMID- 9556476
TI  - GB virus C infection in patients with type II cryoglobulinemia.

PMID- 9556477
TI  - CCR5 genotype and the clinical course of HIV-1 infection.

PMID- 9556478
TI  - Coming to terms with large databases.

PMID- 9556479
TI  - HLA-B27-associated cardiac disease.

PMID- 9556480
TI  - Granulomatous disease in common variable immunodeficiency.

PMID- 9556481
TI  - Granulomatous disease in common variable immunodeficiency.

PMID- 9556482
TI  - Numeracy.

PMID- 9556483
TI  - Tacrolimus to treat pyoderma gangrenosum resistant to cyclosporine.

PMID- 9556484
TI  - Avoidance of tick-borne diseases.

PMID- 9556485
TI  - More on the most terrible of the ministers of death.

PMID- 9556486
TI  - More on the most terrible of the ministers of death.

PMID- 9556487
TI  - A reluctant doctor shopper.

PMID- 9556488
TI  - A reluctant doctor shopper.

PMID- 9556489
TI  - A reluctant doctor shopper.

PMID- 9556490
TI  - A reluctant doctor shopper.

PMID- 9556491
TI  - Federated Council of Internal Medicine's resource guide for residency education.

PMID- 9556492
TI  - Stevie Smith: the caregiver--poet.

PMID- 9556493
TI  - [Surgery videotapes].

PMID- 9556494
TI  - One schedule for all GPs.

PMID- 9556495
TI  - Counts or clusters?

PMID- 9556496
TI  - Evidence based general practice: fact or fancy?

PMID- 9556497
TI  - Special issue on the genetics of obesity.

PMID- 9556499
TI  - Vascular smooth muscle, endothelial regulation and effects of aspirin in
      hypertension.
AB  - Dysfunction of vascular smooth muscle (VSM) is at the center of occlusive
      disorders of the cardiovascular system such as hypertension, atherosclerosis,
      coronary artery disease and hypoxia. In addition to circulating biogenic amines
      and various neurotransmitters originating from the central nervous system and
      endocrine system, various autocoids of arachidonic acid metabolism in the blood
      as well as in the endothelium play an important regulatory role in the
      maintenance of the tone and the contractile function of VSM. A monolayer of
      endothelial cells lining the heart and large blood vessels is responsible for
      producing and releasing both endocrine and paracrine substances such as
      endothelins, nitric oxide, prostaglandins and prostacyclins. Aspirin,
      (acetylsalicylic acid/ASA) an ancient remedy against fever and pain, is emerging
      as an effective drug not only against occlusive disorders but also against
      various cancers and the AIDs virus. During pregnancy induced hypertension (PIH)
      and in occlusive disorders, aspirin provides relief through inhibition of
      cyclooxygenase, an enzyme required for the metabolism of arachidonic acid to
      produce prostaglandins and prostacyclins in platelets and in endothelial cells.
      Because of its unique molecular constitution, synergistic ability and solubility
      in the lipidic environment, various mechanisms of aspirin's actions are being
      currently investigated. In this review, the effect of aspirin on the regulation
      of VSM in the presence and absence of endothelium are discussed.

PMID- 9556498
TI  - Role of E2F in cell cycle control and cancer.
AB  - E2F transcription factors regulate the expression of a number of genes important
      in cell proliferation, particularly those involved in progression through G1 and
      into the S-phase of the cell cycle. The activity of E2F factors is regulated
      through association with the retinoblastoma tumor suppressor protein (Rb) and the
      other pocket proteins, p107 and p130. Binding of Rb, p107 or p130 converts E2F
      factors from transcriptional activators to transcriptional repressors. The
      interplay among G1 cyclins (D-type cyclins and cyclin E), cyclin-dependent
      kinases (cdk4, 6, and 2), cdk inhibitors, and protein phosphatases determines the
      phosphorylation state of the pocket proteins which in turn regulates the ability
      of the pocket proteins to complex with E2F. E2F activity is further regulated
      through direct interactions with other factors, such cyclin A, Sp1, p53 and the
      ubiquitin-proteasome pathway. Deregulated expression of E2F family member genes
      has been shown to induce both inappropriate S phase entry and apoptosis. An
      important role for E2F in the development of cancer is suggested by the finding
      that in most human neoplasias, genetic or epigenetic alterations occur that
      ultimately result in the deregulation of E2F-dependent transcription. This review
      will highlight recent findings on the specific roles of the individual E2F
      species in regulating transcription, proliferation and apoptosis, and discuss the
      growing link between E2F and cancer.

PMID- 9556500
TI  - The neutral theory and natural selection in the HLA region.
AB  - Based on available DNA sequence data in the HLA region of 4 Mb, we review the
      degree of polymorphism at 39 loci of which most are involved in the immune
      system. The extent of nucleotide differences per silent site differs greatly from
      locus to locus. It is exceptionally high at classical MHC loci, intermediate at
      six MHC-related pseudogenes as well as at some loci in class I and II regions,
      and low in the class III region. Different exons of individual MHC loci show also
      different degrees of silent polymorphism; high in the exons encoding for the
      peptide binding region (PBR) and low in the exons encoding for trans-membranes
      and cytoplasmic tails. The degree of polymorphism within MHC allelic lineages is
      not much smaller than that between allelic lineages, contrary to the expectation
      where intra-allelic sequence exchanges are restricted. The observation that many
      allelic lineages at the HLA-DRB1 locus are combinations of distinct motifs in the
      beta pleated sheet and alpha helix of PBR indicates that sequence exchanges occur
      even within exon 2. Semi-quantitative analysis is presented about the rate of
      sequence exchanges between selected and linked neutral regions, although more
      sequence information is necessary to make definite conclusions. The extraordinary
      MHC polymorphism is viewed from the dual function of MHC molecules that controls
      the acquired immune system.

PMID- 9556501
TI  - Fact and fiction 

PMID- 9556502
TI  - Inspiraplex symposium on asthma 

PMID- 9556503
TI  - Airway inflammation and structural changes in airway hyper-responsiveness and
      asthma: an overview.
AB  - Asthma treatment has moved from bronchodilator therapy to an emphasis on anti
      inflammatory therapy. Airway inflammation is believed to induce airway hyper
      responsiveness (AHR) through the release of mediators that increase the airway
      response to agonists. However, the exact contribution of airway inflammation in
      the physiology of airway hyper-responsiveness remains undefined. Structural
      modifications in airways resulting from inflammation may contribute to the
      development and persistence of AHR and the development of asthma. This paper
      reviews some of the main components of airway inflammation and structural changes
      in asthma, and discusses how these processes may interact to modify airway
      function and induce respiratory symptoms.

PMID- 9556504
TI  - Mast cells in asthma.

PMID- 9556505
TI  - Lymphocytes in asthma.

PMID- 9556507
TI  - Neuropeptides: do they have a role in the pathogenesis of asthma?

PMID- 9556506
TI  - Cytokine expression in bronchial asthma.

PMID- 9556508
TI  - Eicosanoids and asthma.

PMID- 9556509
TI  - Relationship between airway smooth muscle dysfunction and airway inflammation in
      asthma.

PMID- 9556511
TI  - Three-dimensional production of bronchi in vitro.

PMID- 9556510
TI  - Animal models of airway inflammation and remodelling.

PMID- 9556512
TI  - Remodelling of the extracellular matrix in asthma: proteoglycan synthesis and
      degradation.

PMID- 9556513
TI  - Airway inflammation and remodelling in asthma: airway epithelial cells.

PMID- 9556514
TI  - Bronchial myofibroblasts and tissue remodelling in asthma.

PMID- 9556515
TI  - Increased amount of airway smooth muscle does not account for excessive
      bronchoconstriction in asthma.

PMID- 9556516
TI  - Mechanisms of corticosteroid resistance in asthma: role of airway remodelling.

PMID- 9556517
TI  - Irritant-induced asthma and reactive airways dysfunction syndrome.

PMID- 9556518
TI  - Asthma therapy: effects on airway inflammation and remodelling.

PMID- 9556519
TI  - Protein folding: nucleation and compact intermediates.
AB  - Experimental and theoretical studies of protein folding have led now to
      understanding some basic principles of this process. In the simplest case of two
      state folding it starts from the formation of the folding nucleus which
      immediately grows up embracing the whole protein molecule. However, typically
      folding occurs through a compact intermediate which has some native-like features
      of its 3D-structure. It is possible that also in these cases the folding nucleus
      is involved in the transition state between unfolded chain and compact
      intermediate.

PMID- 9556520
TI  - Protein folding assisted by the GroEL/GroES chaperonin system.
AB  - The chaperonin system GroEL/GroES assists in the folding of proteins in the
      bacterial cytosol. Recent applications of biophysical techniques for the
      structural analysis of GroEL, GroES, and chaperonin-bound protein folding
      intermediates have provided the basis for understanding the molecular mechanism
      of GroEL/GroES action. GroEL, a double-ring complex, binds unfolded proteins at
      its inner ring surface. Protein folding proceeds in the central cavity of GroEL,
      after dissociation of the polypeptide has been triggered by ATP hydrolysis in
      GroEL. Premature release of unfolded protein into external solution is prevented
      by binding of the cofactor GroES on top of the GroEL cylinder, resulting in an
      enclosed cage. Upon ATP-dependent dissociation of GroES, substrate protein is
      eventually released from GroEL in a native or native-like conformation. While
      current in vitro results about the structure, function, and molecular mechanism
      of GroEL/GroES-assisted protein folding have led to a quite detailed picture of
      this complex process, the extent to which the GroEL/GroES system actually
      participates in the folding of newly-synthesized proteins in the cell is less
      defined and remains a subject for further studies. Ingenious biochemical and
      genetic approaches will be necessary to show whether our current view of
      chaperonin action indeed accurately reflects its modus operandi inside a living
      cell.

PMID- 9556521
TI  - GroE chaperonin-assisted folding and assembly of dodecameric glutamine
      synthetase.
AB  - The folding and assembly of Escherichia coli dodecameric glutamine synthetase is
      facilitated by the E. coli GroE chaperonins, GroEL and GroES. Since endogenous
      glutamine synthetase monomers are bound to GroEL immediately after cell lysis and
      are assembly competent, this strongly suggests that glutamine synthetase is an
      authentic substrate of the GroE chaperonins. At physiological temperatures, the
      in vitro reactivation of glutamine synthetase increases from 10 to 70-80% of the
      original activity when the chaperonin GroEL is included. Although nucleotide
      binding is sufficient to dissociate assembly competent glutamine synthetase
      monomers from GroEL, the addition of GroES substantially accelerates the
      dissociation, assembly, and reactivation. The interactions of glutamine
      synthetase monomers with the activated chaperonin are transient (t1/2 = 10 sec)
      and these monomers can be released from GroEL at high concentrations without
      misfolding or inappropriate aggregation. It has been found that the nucleotide
      induced conformational change of GroEL is critical for folding success of
      glutamine synthetase because the simple displacement of glutamine synthetase
      monomers from the GroEL chaperonin with another protein substrate inhibits
      reactivation. During glutamine synthetase refolding, the "high affinity"
      nucleotide-free GroEL is most efficient in preventing initial folding
      intermediates from partitioning to off-pathway folding routes. Interestingly, the
      more physiologically relevant "low affinity" nucleotide-bound ((ATP/ADP) GroEL-
      GroES) complex is not as efficient at capturing the initial folding intermediates
      of glutamine synthetase. In contrast to glutamine synthetase, non-authentic
      "model" substrates such as mammalian mitochondrial rhodanese and mitochondrial
      malate dehydrogenase show no differences in folding efficiencies with either the
      "low affinity" or "high affinity" complexes. Besides the nature of the chaperonin
      complex itself, the mechanism of GroE-assisted folding is determined by the
      folding environment and, most importantly, by initial interactions of chaperonins
      with folding intermediates. Glutamine synthetase interacts only transiently with
      chaperonin complexes, while most of the "model" proteins exhibit relatively long
      interactions times. It may be indicative of a specific evolutionary selected
      mechanism of chaperonin-assisted folding (optimizing the folding kinetics),
      different from that observed with non-authentic chaperonin substrates. Since the
      kinetics of protein folding depends heavily on the solution environment, studies
      involving in vivo chaperonin substrates under conditions that closely mimic those
      found in the cell will be required to define and solve the physiologically
      relevant kinetic mechanism of chaperonin-assisted folding.

PMID- 9556522
TI  - Chaperones in bacteriophage T4 assembly.
AB  - Protein folding in the cell is controlled at the levels of translation and post
      translational modification, depends on a number of conserved proteins known as
      chaperones, and is catalyzed by specific enzymes, such as protein disulfide
      isomerase and peptidyl prolyl cis-trans isomerase. The chaperones stabilize
      folding intermediates and participate in assembly and disaggregation of
      supramolecular structures. Bacteriophage T4 is an especially convenient system
      for studying of protein folding mechanisms, since its genome encodes several
      virus-specific chaperones. In this review, the chaperones of phage T4 that take
      part in capsid formation (gp31 and gp40) and in folding and assembly of virion
      tail fibers (gp38, gp57A) have been considered. Protein encoded by gene 31
      completely substitutes co-chaperonin GroES of the host cell in folding of the
      major capsid protein, gp23, aided by chaperonin GroEL. The product of gene 40,
      which is homologous to analogs of eukaryotic GroEL and peptidyl prolyl cis-trans
      isomerase, participates in assembly of gp20 while the formation of procapsid
      connector. The chaperone encoded by gene 57A is essential for folding and
      oligomerization of both long and short phage tail fibers. gp38, together with
      gp57A, participates in the formation of the distal part of the long fibers. This
      protein seems to represent a principally new group of chaperones that change
      steric structure of folded polypeptide. One phage chaperone, fibritin, encoded by
      gene wac (whiskers antigen control) and taking part in assembly the subunits of
      the long tail fibers is a constituent of the virion. Fibritin is a convenient
      model for studying mechanisms of folding and oligomerization of fibrous proteins
      due to its labile triple-stranded alpha-helical coiled-coil structure.

PMID- 9556523
TI  - Isomerase and chaperone activities of protein disulfide isomerase are both
      required for its function as a foldase.
AB  - Protein disulfide isomerase (PDI) is not only an isomerase catalyzing the
      formation of native disulfide bond(s) of nascent peptide, but also a molecular
      chaperone assisting chain folding. The intrinsic chaperone activity of PDI is
      independent of its isomerase activity as shown by its ability of promoting in
      vitro reactivation and suppressing aggregation during refolding of denatured
      proteins containing no disulfide. The -CGHC- active sites of PDI are not required
      for its chaperone activity and a mutant PDI with no isomerase activity does
      function in vitro and in vivo. The peptide binding site of PDI is responsible for
      its chaperone activity. Both isomerase and chaperone activities are required for
      PDI to function as a foldase in assisting protein folding, in other words, the
      foldase activity of PDI consists of both isomerase and chaperone activities.

PMID- 9556524
TI  - Artificial chaperone-assisted refolding of proteins.
AB  - A new two-step procedure of protein refolding in vitro, proposed by Rozema and
      Gellman and named artificial chaperone-assisted refolding, is discussed. The new
      approach has been inspired by the two-step mechanism of the GroE system. In the
      first step, the protein is captured by a detergent under conditions that would
      normally lead to irreversible protein aggregation (heating or denaturant
      removal). In the second step, removal of detergent from the protein--detergent
      complex is triggered by addition of a cyclodextrin which is capable of forming
      "inclusion complexes" with detergent, allowing the protein to refold. The protein
      refolded with artificial chaperones (detergent and cyclodextrin) may be purified
      via a two-step protocol. After refolding was complete, the solution was passed
      through a 0. 22-micro(m) filter, to remove aggregated protein, and then through a
      M = 10 kD cutoff filter. The second filtration was intended to allow the low
      molecular-weight artificial chaperones to pass, but to retain the refolded
      enzyme. The application of the above procedure for refolding of carbonic
      anhydrase B from human erythrocytes, hen egg white lysozyme, pig heart citrate
      synthase, and creatine kinase from rabbit skeletal muscles (MM isoenzyme) is
      discussed.

PMID- 9556525
TI  - Effect of natural ligands on the structural properties and conformational
      stability of proteins.
AB  - The effect of natural ligands on the structural properties and conformational
      stability of proteins is reviewed. It is shown that the range of possible
      structural transformations induced in a protein molecule by ligand release is
      very wide and virtually does not depend on the nature of the protein or that of
      the ligands. Ligand-free forms of protein are classified from the viewpoint of
      structural property changes of a protein molecule.

PMID- 9556526
TI  - Modeling of irreversible thermal protein denaturation at varying temperature. I.
      The model involving two consecutive irreversible steps.
AB  - The model of thermal protein denaturation involving two consecutive irreversible
      steps has been analyzed. The equation describing the dependence of excess heat
      capacity (Cpex) on temperature (T) under a constant scanning rate has been
      obtained and used for construction of theoretical Cpex versus T profiles. The
      change in the shape of theoretical profiles at varied Arrhenius equation
      parameters, ratio for enthalpies of the first and second steps, and the scanning
      rate have been studied. It has been shown that formal use of one-step model does
      not provide adequate information about kinetic features of the process in the
      case of protein denaturation following the mechanism involving two consecutive
      irreversible steps.

PMID- 9556527
TI  - Application of the method of thermal denaturation for investigation of alpha
      chymotrypsin adducts with poly.
AB  - The thermostability of conjugates, non-covalent complexes and mixtures of alpha
      chymotrypsin (alpha-ChT) with poly(alkylene oxides)--poly(ethylene glycol) (PEG)
      with molecular mass of 1.9 kD and diblock copolymers of ethylene and propylene
      oxides (proxanols)--has been investigated. It was shown that the addition of PEG
      in concentration up to 2 wt. % to the solution of alpha-ChT did not affect the
      rate of the enzyme thermoinactivation. Meanwhile the addition of proxanol in the
      same concentration resulted in twofold decrease in the rate constant for the slow
      inactivation step, k2. Even more pronounced decrease in the thermoinactivation
      rate was observed for alpha-ChT--proxanol complexes obtained by heating or under
      the action of high pressure. The general tendency in the behavior of complexes of
      both types was the decrease in the k2 constant as the temperature or pressure
      used for complex preparation increased. The highest stabilizing effect was
      observed for complex obtained by heating up to 52 degreesC and containing maximal
      number of polymer chains (molar ratio proxanol/alpha-ChT was 10). For this
      complex fourfold decrease in the k2 value was observed. Covalent attachment of
      PEG or proxanol to enzyme gives maximal stabilizing effect with up to tenfold
      decrease in the k2 value. The investigation of the thermal denaturation kinetics
      of alpha-ChT and its adducts with poly(alkylene oxides) by means of fluorescence
      spectroscopy has shown that the presence of polymer chains practically does not
      affect the rate of protein denaturation registered by the decrease in the
      intensity of protein fluorescence. The polymer chains, probably, diminish the
      rate of melting of the active site-containing region of the protein molecule. At
      the same time, the overall denaturation rate is independent of the presence of
      polymer chains in the vicinity of the protein globule.

PMID- 9556528
TI  - Decrease of dielectric constant transforms the protein molecule into the molten
      globule state.
AB  - The effect of organic solvents of different nature (alcohols, amides, and cyclic
      ethers) on the structural properties of beta-lactoglobulin was studied by
      circular dichroism and fluorescence spectroscopy. It is shown that the protein
      molecule undergoes at least two consecutive conformational transitions upon
      increase of the organic solvent concentration. Denaturation of the protein
      molecule occurs in the first step and a transition into the highly helical non
      compact state in the second. In other words, under such conditions a compact
      denatured intermediate state is formed with a pronounced secondary structure,
      i.e., a molten globule-like state. It is shown that decrease of the dielectric
      constant of the media is responsible for structural changes of the protein
      molecule.

PMID- 9556529
TI  - Structural effect of association on protein molecules in partially folded
      intermediates.
AB  - Fluorescence and circular dichroism spectroscopy, small angle X-ray scattering
      and high performance liquid gel filtration have shown that oligomerization
      considerably affects the structural properties and conformational stability of
      partially folded intermediates of staphylococcal nuclease. Conformational
      transitions induced by different anions and association in the acid-unfolded
      protein are described. It is shown that association of non-native conformations
      of the protein molecule can be an additional structuring factor. The
      corresponding folding schemes and phase diagrams are suggested.

PMID- 9556530
TI  - Structural properties of staphylococcal nuclease in oligomeric A-forms.
AB  - Association affects the structural properties of different partially folded
      conformations of staphylococcal nuclease induced by anions of different nature.
      It is shown that oligomerization induces new structural levels in non-native A
      forms. A close structural similarity between the monomeric A2 and the dimeric
      (A1)2 forms as well as between the monomeric A3 and oligomeric [(A1)2]M and [A2]M
      forms is established. This suggests that association of a protein molecule in
      partially folded conformations can be an additional structure forming factor.

PMID- 9556531
TI  - Equilibrium unfolding of partially folded staphylococcal nuclease A2- and A3
      forms is accompanied by the formation of an intermediate state.
AB  - Structural properties of an equilibrium intermediate formed upon urea-induced
      unfolding of more ordered staphylococcal nuclease A-forms (A2 and A3) are
      studied. The effect of association on the structural properties and
      conformational stability of this unfolding intermediate is also considered. A
      close structural similarity (including tendency for association) is shown between
      this intermediate and the least ordered A1-form, induced in the acid-unfolded
      nuclease by moderate sulfate or chloride concentrations.

PMID- 9556532
TI  - Thermodynamic stability of immunoglobulins and allosteric interactions with
      ferritin and protein A: distinct properties of the two antibodies of IgG2a
      subclass.
AB  - The two anti-ferritin monoclonal antibodies of mouse IgG2a subclass, G10 and F11,
      are described that have similar affinity to human spleen ferritin and identical
      protein A-binding affinity. Antigen binding was shown to change significantly the
      protein A-binding parameters of the IgG2a antibodies. Antigen-induced
      conformational changes result in enhanced protein A-binding affinity of the G10
      antibody while reduced affinity of the F11 antibody. Antigen binding does not
      change inherently low affinity of the anti-ferritin IgG1 antibody C5 to protein
      A. Differential scanning calorimetry revealed that the enthalpy and Gibbs free
      energy of denaturation for G10 was respectively by 19 and 29% higher than the
      corresponding parameters for F11. The lower structural energetics of F11 is
      associated with the lack of a calorimetrically revealed folding unit that may be
      responsible for distinct interaction between the antigen-binding and protein A
      binding sites. This work provides experimental demonstration of the fact that
      functionally significant interactions between the two spatially remote
      recognition sites in antibodies of the same heavy chain isotype can be modulated
      by relatively small structural variations that also result in different
      thermodynamic stability.

PMID- 9556533
TI  - Protein sizes and stoichiometry in the chaperone SecB--RBPTI complex estimated by
      ANS fluorescence.
AB  - Interaction of the SecB E. coli chaperone with model precursor protein, the
      reduced form of bovine pancreatic trypsin inhibitor (RBPTI), in aqueous solution
      was studied using ANS fluorescence. Binding of RBPTI by SecB-ANS led to an
      increase and blue shift in the ANS fluorescence. Two ANS emission centers exist
      in the proteins and their complex: the short-lived center (lifetime of
      approximately 1 nsec) where ANS is strongly quenched by polar amino acid residues
      and the long-lived center (6-12 nsec) where ANS emits from the hydrophobic
      pocket. Estimation of the volumes and diameters of RBPTI, SecB, and the SecB-
      RBPTI complex using fluorescence lifetime and polarization of ANS by a modified
      Levshin--Perrin equation was done. Effective diameter of the SecB equals to 33.4
      A. The diameter of the SecB--RBPTI complex is 49.8 A. The volume of the complex
      equals to sum of volumes of one tetrameric SecB and four RBPTI molecules. The
      binding of RBPTI molecules into the tetramer SecB is not an insertion to a "pore"
      without increase of the protein sizes, but "paste" of four polypeptide molecules
      to four subunits of SecB.

PMID- 9556534
TI  - Reactivation of sea-urchin sperm flagella induced by rapid photolysis of caged
      ATP.
AB  - Sea-urchin sperm flagella in a state of rigor were reactivated by rapid
      photolysis of caged ATP. After a time lag of 11-17 ms, all bends in the axonemes
      present during rigor began to be propagated towards the tip as if their
      propagation had not been interrupted. This result suggests that the site-specific
      activity of dyneins along the length of the axoneme is preserved even during
      rigor states when ATP is absent and that regulation of the activity can be
      restarted immediately with a new cycle of ATP turnover. During the starting
      transient, pre-existing rigor waves in the distal region were propagated without
      a change in the maximal shear angle until they disappeared at the tip. This was
      more evident when the rapid reactivation was triggered in high-viscosity
      solution, in which only the form of new bends was greatly affected by viscous
      load. After reactivation, the velocity of microtubule sliding increased and
      reached a plateau within 28 ms. This time course reflects the rate of force
      generation by dynein in situ.

PMID- 9556535
TI  - Muscle power output limits fast-start performance in fish.
AB  - Fast-starts associated with escape responses were filmed at the median habitat
      temperatures of six teleost fish: Notothenia coriiceps and Notothenia rossii
      (Antarctica), Myoxocephalus scorpius (North Sea), Scorpaena notata and Serranus
      cabrilla (Mediterranean) and Paracirrhites forsteri (Indo-West-Pacific Ocean).
      Methods are presented for estimating the spine positions for silhouettes of
      swimming fish. These methods were used to validate techniques for calculating
      kinematics and muscle dynamics during fast-starts. The starts from all species
      show common patterns, with waves of body curvature travelling from head to tail
      and increasing in amplitude. Cross-validation with sonomicrometry studies allowed
      gearing ratios between the red and white muscle to be calculated. Gearing ratios
      must decrease towards the tail with a corresponding change in muscle geometry,
      resulting in similar white muscle fibre strains in all the myotomes during the
      start. A work-loop technique was used to measure mean muscle power output at
      similar strain and shortening durations to those found in vivo. The fast Sc.
      notata myotomal fibres produced a mean muscle-mass-specific power of 142.7 W kg-1
      at 20 degrees C. Velocity, acceleration and hydrodynamic power output increased
      both with the travelling rate of the wave of body curvature and with the habitat
      temperature. At all temperatures, the predicted mean muscle-mass-specific power
      outputs, as calculated from swimming sequences, were similar to the muscle power
      outputs measured from work-loop experiments.

PMID- 9556536
TI  - Optimal shortening velocity (V/Vmax) of skeletal muscle during cyclical
      contractions: length-force effects and velocity-dependent activation and
      deactivation.
AB  - The force-velocity relationship has frequently been used to predict the
      shortening velocity that muscles should use to generate maximal net power output.
      Such predictions ignore other well-characterized intrinsic properties of the
      muscle, such as the length-force relationship and the kinetics of activation and
      deactivation (relaxation). We examined the effects of relative shortening
      velocity on the maximum net power output (over the entire cycle) of mouse soleus
      muscle, using sawtooth strain trajectories over a range of cycle frequencies. The
      strain trajectory was varied such that the proportion of the cycle spent
      shortening was 25, 50 or 75 % of the total cycle duration. A peak isotonic power
      output of 167 W kg-1 was obtained at a relative shortening velocity (V/Vmax) of
      0.22. Over the range of cyclical contractions studied, the optimal V/Vmax for
      power production ranged almost fourfold from 0.075 to 0.30, with a maximum net
      power output of 94 W kg-1. The net power output increased as the proportion of
      the cycle spent shortening increased. Under conditions where the strain amplitude
      was high (i.e. low cycle frequencies and strain trajectories where the proportion
      of time spent shortening was greater than that spent lengthening), the effects of
      the length-force relationship reduced the optimal V/Vmax below that predicted
      from the force-velocity curve. At high cycle frequencies and also for strain
      trajectories with brief shortening periods, higher rates of activation and
      deactivation with increased strain rate shifted the optimal V/Vmax above that
      predicted from the force-velocity relationship. Thus, the force-velocity
      relationship alone does not accurately predict the optimal V/Vmax for maximum
      power production in muscles that operate over a wide range of conditions (e.g.
      red muscle of fish). The change in the rates of activation and deactivation with
      increasing velocity of stretch and shortening, respectively, made it difficult to
      model force accurately on the basis of the force-velocity and length-force
      relationships and isometric activation and deactivation kinetics. The
      discrepancies between the modelled and measured forces were largest at high cycle
      frequencies.

PMID- 9556537
TI  - Morphometric and biochemical characteristics of ventricular hypertrophy in male
      rainbow trout (Oncorhynchus mykiss).
AB  - We examined the morphometric and biochemical effects of ventricular hypertrophy
      in male rainbow trout (Oncorhynchus mykiss) during sexual maturation. Our
      investigation focused on characterizing the growth of ventricular layers, on
      cardiomyocyte dimensions (length, cross-sectional area and cell volume) and on
      the activities of enzymes involved in intermediary metabolism. Relative ventricle
      mass (100 x ventricle mass/body mass) increased by as much as 2.4-fold during
      sexual maturation [as defined by an increasing gonadosomatic index (100 x gonad
      mass/body mass)], and this resulted in an increased proportion of epicardium
      relative to endocardium. Ventricular enlargement was associated with increased
      length (+31 %) and transverse cross-sectional area (+83 %) of cardiomyocytes,
      which resulted in an expansion of up to 2.2-fold in mean myocyte volume (from
      1233 to 2751 micron3). These results indicate that sexual maturation induces
      ventricular enlargement through myocyte hypertrophy. Cell length and cross
      sectional area were similar in both myocardial layers, and myocytes were
      elliptical rather than circular in transverse cross section. Ventricular
      hypertrophy did not alter transverse cell shape, perhaps reflecting the
      maintenance of short diffusion distances for small molecules as cells
      hypertrophy. Myocyte hypertrophy could not account entirely for the sevenfold
      range of ventricle masses from different-sized fish, indicating that myocyte
      hyperplasia contributes substantially to ventricular growth as trout grow.
      Measurements of the maximal activities of metabolic enzymes demonstrated that
      ventricular hypertrophy was associated with (1) higher epicardial but not
      endocardial activities of citrate synthase (by 23 %) and beta-hydroxyacyl-CoA
      dehydrogenase (by 20 %); (2) lower activities of hexokinase (by 50 %) in both
      layers, and (3) no change in lactate dehydrogenase or pyruvate kinase activities,
      which were also similar between layers. These results suggest that the energetic
      needs of the hypertrophied trout ventricle may be met through increased reliance
      on fatty acid oxidation, particularly by the endocardium, but decreased reliance
      on glucose as a metabolic fuel in both layers.

PMID- 9556538
TI  - Analyses of cDNA and recombinant protein for a potent vasoactive protein in
      saliva of a blood-feeding black fly, Simulium vittatum.
AB  - A cDNA was cloned from the salivary glands of a blood-feeding black fly Simulium
      vittatum. The encoded protein has been given the name Simulium vittatum erythema
      protein or SVEP, because of its ability to increase blood perfusion in skin
      capillaries, resulting in the well-characterized erythema of black fly bites. The
      full-length cDNA contains 548 base pairs which encode 152 amino acid residues of
      the nascent protein. Post-translational processing produces a mature, secreted
      protein of 133 residues with a molecular mass of 15.4 kDa. Recombinant SVEP
      (rSVEP) was produced in a baculovirus expression system and purified by a one
      step reversed-phase HPLC procedure. Analyses of physical properties and
      biological potency demonstrated fidelity of rSVEP to the native protein.
      Recombinant SVEP relaxed rabbit aorta preparations when preconstricted with 2
      micromol l-1 phenylephrine or 25 mmol l-1 K+ but not with 60 mmol l-1 K+.
      Further, the rSVEP-induced relaxation response of phenylephrine-constricted aorta
      was inhibited by glibenclamide (10 micromol l-1), suggesting that at least part
      of its action to relax smooth muscle may result from the opening of ATP-dependent
      K+ channels. SVEP is a novel salivary-gland-derived vasoactive protein that may
      be essential for blood feeding by black flies and could potentially enhance
      transmission of filarial parasites.

PMID- 9556540
TI  - Factors contributing to seasonal increases in inoculative freezing resistance in
      overwintering fire-colored beetle larvae dendroides canadensis 
AB  - The insects and microarthropods that vary seasonally in susceptibility to cross
      cuticular inoculation by external ice (inoculative freezing) represent a
      phylogenetically diverse group; however, few studies have explored possible
      mechanisms experimentally. This study documents seasonally variable inoculative
      freezing resistance in Dendroides canadensis beetle larvae and combines
      immunofluorescence, in vivo removal of epicuticular lipids and in vitro chamber
      studies to explore the roles of seasonal modification in the cuticle and in
      epidermal and hemolymph antifreeze proteins (AFPs). Seasonal cuticular
      modifications contribute to the inhibition of inoculative freezing since more
      cold-hardy larvae froze inoculatively when epicuticular waxes were removed with
      hexane and, in in vitro chamber experiments, cuticle patches (with the underlying
      epidermis removed) from winter larvae provided greater protection from
      inoculative freezing than did cuticle patches from summer larvae. The results
      indicate that seasonal modifications in epidermal and hemolymph AFPs contribute
      most strongly to the inhibition of inoculative freezing. Subcuticular epidermal
      AFPs were present in immunocytochemically labeled transverse sections of winter
      larvae but were absent in summer ones. Winter integument patches (cuticle with
      epidermis) were more resistant to inoculative freezing than were summer
      integument patches. Integument patches resisted inoculative freezing as well as
      live winter-collected larvae only when hemolymph AFP was added. The results also
      suggest that some integumentary ice nucleators are removed in cold-hardy larvae
      and that AFP promotes supercooling by inhibiting the activity of these
      nucleators.

PMID- 9556539
TI  - Kinematic models of the buccal mass of Aplysia californica.
AB  - The feeding behavior of the marine mollusc Aplysia californica is an intensively
      studied model system for understanding the neural control of behavior. Feeding
      movements are generated by contractions of the muscles of the buccal mass. These
      muscles are internal and cannot be visualized during behavior. In order to infer
      the movements of the muscles of the buccal mass, two kinematic models were
      constructed. The first kinematic model assumed that the complex consisting of the
      pincer-like radula and the underlying odontophore was spherical in shape. In this
      model, the radula/odontophore was moved anteriorly or posteriorly and the more
      superficial buccal muscles (I1/I3 and I2) were fitted around it. Although the
      overall buccal mass shapes predicted by this model were similar to those observed
      in vivo during protraction, the shapes predicted during retraction were very
      different. We therefore constructed a second kinematic model in which the shape
      of the radula/odontophore was based on the shapes assumed by those structures in
      vitro when they were passively forced into protraction, rest or retraction
      positions. As each of these shapes was rotated, the second kinematic model
      generated overall shapes of the buccal mass that were similar to those observed
      in vivo during swallowing and tearing, and made predictions about the antero
      posterior length of the buccal mass and the relative location of the lateral
      groove. These predictions were consistent with observations made in vivo and in
      vitro. The kinematic patterns of intrinsic buccal muscles I1 and I2 in vivo were
      estimated using the second model. Both models make testable predictions with
      regard to the functions and neural control of intrinsic buccal muscles I2 and I3.

PMID- 9556541
TI  - Defensive ink pigment processing and secretion in Aplysia californica:
      concentration and storage of phycoerythrobilin in the ink gland.
AB  - The marine snail Aplysia californica obtains its defensive ink exclusively from a
      diet of red seaweed. It stores the pigment (phycoerythrobilin, the red algal
      photosynthetic pigment, r-phycoerythrin, minus its protein) in muscular ink
      release vesicles within the ink gland. Snails fed a diet of green seaweed or
      romaine lettuce do not secrete ink and their ink-release vesicles are largely
      devoid of ink. Successive activation of individual ink-release vesicles by ink
      motor neurons causes them to secrete approximately 55 % of their remaining ink
      (similar to the percentage of ink reserves released from the intact gland). The
      peripheral activation of vesicles appears to be cholinergic: 70 % of isolated
      vesicles were induced to squeeze ink from their valved end by solutions of
      acetylcholine at concentrations of 0.5 mmol l-1 or below. Ultrastructural
      analysis commonly found three cell types in the ink gland. The RER cells, the
      most numerous, were characterized by an extensive rough endoplasmic reticulum
      with greatly distended cisternae. This cell type is probably the site for
      synthesis of the high molecular mass protein of secreted ink. The granulate
      cells, less common than RER cells, had nuclear and cell areas significantly
      larger than those of RER cells. In addition, granulate cells of red-algal-fed
      snails had 4-14 vacuoles that contained electron-dense material with staining
      characteristics similar to that of ink in mature ink-release vesicles. The
      granulate cell's plasma membrane was regularly modified into grated areas, which
      both localized and expanded the surface area for coated vesicle formation and
      provided a sieve structure that prevented large particles in the hemolymph either
      from being taken up by, or from occluding, the coated vesicles. Electron-dense
      particles within coated vesicles were similar in size to those in granulate
      vacuoles but larger (on average by approximately 1 nm) than those that make up
      the ink. In green-seaweed-fed snails, granulate cells and their vacuoles were
      present but the vacuoles were empty. The third cell type, the vesicle cell,
      expands markedly, with its nucleus enlarging concurrent with cell growth until it
      is on average 50 times larger in cross-sectional area than the nuclei of either
      RER or granulate cells; the cytoplasm eventually becomes filled with ink, which
      obscures the mitochondria, vacuoles and nucleus. Continued cell expansion ceases
      with the appearance of an encircling layer of muscle and 1-3 layers of cells of
      unknown origin, thereby becoming the ink-release vesicle itself. The absorption
      spectra of the soluble contents of mature ink-release vesicles from snails fed
      red algae had peaks characteristic of the red algal pigment r-phycoerythrin
      or/and phycoerythrobilin. Immunogold localization of r-phycoerythrin showed no
      statistical difference in the amount of label within the ink-release vesicles,
      RER or granulate cell types. Furthermore, there was no localization of
      phycoerythrin immunoreactivity within the various cellular compartments of either
      the RER or granulate cells (nucleus, endoplasmic reticulum, mitochondria,
      vacuoles). Immunogold labeling in the ink gland ranged from 11 to 16 % of that
      for the digestive vacuoles of the rhodoplast digestive cells lining the tubules
      of the digestive gland. Our observations suggest (a) that the main form of the
      ink pigment in the gland is phycoerythrobilin or/and a non-antigenic form of
      phycoerythrin, and (b) that separation of the bilin from phycoerythrin (or its
      modification so that it is no longer antigenic) occurs before it reaches the ink
      gland, probably within the vacuoles of the rhodoplast digestive cells of the
      digestive gland. We propose the following model. The ink pigment,
      phycoerythrobilin, is cleaved from its protein in rhodoplast digestive vacuoles
      in the digestive gland. (ABSTRACT TRUNCATED)

PMID- 9556542
TI  - Species-specific action and distribution of tachykinin-related peptides in the
      foregut of the cockroaches Leucophaea maderae and Periplaneta americana.
AB  - Nine tachykinin-related peptides (TRPs) have been isolated from the brain and
      intestine of the cockroach Leucophaea maderae. In the present investigation, two
      of the nine TRPs, LemTRP 1 and 5, were tested for their ability to stimulate
      contractions in the foregut of the cockroaches L. maderae and Periplaneta
      americana in vitro. The two LemTRPs and the related locust peptide
      locustatachykinin I (LomTK I) induced contractions in the foregut of P. americana
      in a dose-dependent manner, but had no myostimulatory action in L. maderae. A
      half-maximal response for the LemTRPs and LomTK I was obtained at 5x10(-9)mol l
      1. In both species, the neuropeptide proctolin stimulated foregut contractions.
      Using an antiserum to LomTK I, we demonstrated that in both species there are
      LomTK-like-immunoreactive (LomTK-LI) cell bodies and fibers within the ganglia
      and nerves of the stomatogastric nervous system. However, correlated with the
      species-specific action of the TRPs, we found efferent LomTK-LI nerve fibers
      supplying muscle fibers in the foregut of P. americana, but not in L. maderae. In
      both cockroach species, there is a rich supply of proctolin-immunoreactive fibers
      to the foregut muscle. Some of the LomTK-LI fibers supplying the P. americana
      foregut muscle contain co-localized proctolin immunoreactivity. These fibers
      appear to be derived from a large cell body in the frontal ganglion which also
      displayed co-localized immunoreactivities. Since TRP-containing neurons are
      restricted to the nerves and ganglia of the stomatogastric nervous system both in
      P. americana and L. maderae, TRPs may be involved in the control of foregut
      movements in both species, but in P. americana the control may be more complex
      with the additional peripherally projecting LomTK-LI neurons.

PMID- 9556543
TI  - Cyclic-AMP-induced water uptake in a moth ovary: inhibition by bafilomycin and
      anthracene-9-carboxylic acid.
AB  - The ion physiology of osmotic swelling and a consequent loss of epithelial
      patency was examined in the ovaries of the moth Hyalophora cecropia. After 30 min
      in the presence of an activator of cyclic-AMP-dependent protein kinase (PKA), the
      membrane potentials of both oocyte and follicle cells had hyperpolarized by
      approximately 30 %, cytoplasmic pH had dropped from 7.26 to 7.06, a normally low
      Cl- conductance had increased and the follicle cells had begun to swell. Since
      ion distribution studies have indicated that conductance increases should
      depolarize membranes in this system, it is proposed that hyperpolarization may be
      effected by an azide-inhibitable component of the membrane potential. Nanomolar
      levels of bafilomycin, an inhibitor of H+ V-ATPase, blocked the active component
      and prevented osmotic swelling in response to PKA activation. Under a variety of
      circumstances, correlations were seen between membrane potential and cytoplasmic
      pH, suggesting that substrate availability to the proton pump may contribute to
      hyperpolarization. H+ V-ATPases are known to energize ion and water transport
      across many epithelia, but in this case they generate water absorption by the
      epithelium. The increase in Cl- conductance was also required for the swelling
      response: the Cl- channel blocker anthracene-9-carboxylic acid prevented both
      swelling and hyperpolarization, as did Cl- substitution in the medium.
      Differences in isotope loading rates between 36Cl- and 86Rb+ suggested that,
      after PKA activation, Cl- functions other than as a counterion for K+ uptake.

PMID- 9556544
TI  - Sound production in the collared dove: a test of the 'whistle' hypothesis 
AB  - The mechanism of sound production in the collared dove Streptopelia decaocto was
      studied to test the validity of the 'whistle' model and to analyze the role of
      vocal tract resonances. In this study, the vocalizations of six male adult doves
      were recorded both in normal air and in a mixture of 80 % helium and 20 % oxygen
      (heliox). Depending on the way in which the syrinx operates, the spectral
      structure of the vocalizations is expected to show specific changes in heliox.
      The effects of heliox differed substantially depending on the type of vocal
      element. Except for a significant decrease in amplitude, unmodulated elements,
      i.e. elements with a constant frequency, were relatively unaffected by heliox. In
      contrast, modulated elements, i.e. elements with an abrupt increase in frequency,
      showed a gradual increase in frequency with increasing helium concentration. This
      specific increase in frequency stopped when the modulation frequency was 1.5
      times the base frequency, even when the helium concentration was increased
      further. In some individuals, a frequency band of half the base frequency was
      also observed. In general, the proportion of modulated elements also showed a
      significant decrease. The lack of change in the fundamental frequency of the
      unmodulated elements and in the base frequency of the modulated elements
      indicates that these vocalizations are not produced like a whistle. It is more
      likely that they are the result of vibration of the syringeal membranes.
      Generally, vocal tract resonances do not play an active role in the modification
      of vocalizations, although they might enhance the fundamental frequency
      passively. The results suggest that the almost pure tonal vocalizations are
      produced as such in the syrinx and undergo limited modification when passing
      through the vocal tract. The effect of heliox on the modulation frequency
      suggests (1) that different sound-producing mechanisms may underlie different
      types of vocalizations, and (2) that resonance properties of the vocal system may
      be involved in the production or modification of the modulation frequency.

PMID- 9556545
TI  - Proline powers pre-flight warm-up in the african fruit beetle pachnoda sinuata 
AB  - We investigated thoracic temperatures (Tth) during different activities of the
      endothermic fruit beetle Pachnoda sinuata and analysed which energy substrates
      are used for the pre-flight warm-up of its flight muscles. Pachnoda sinuata
      elevates its Tth prior to take-off either by basking in the sun or by warming
      endothermically to a narrow range around 34 degreesC. During lift-generating
      tethered flight at low ambient temperatures (Ta=25 degreesC), Tth of P. sinuata
      decreases steadily until it reaches 28 degreesC, which is not sufficiently high
      to sustain flight. Tth remains stable during lift-generating tethered flight at
      high Ta (31 degreesC). Wingbeat frequency (fw) is dependent on Tth: when Tth
      declines, fw decreases in a linear manner. The proline concentrations in the
      haemolymph and flight muscles decrease during warm-up. In contrast, the
      carbohydrate levels in the haemolymph and flight muscles are not affected by the
      warm-up process, while the glycogen level of the flight muscles declines
      significantly during the first 10 s of lift-generating tethered flight. This
      suggests that the energy for endothermic warm-up is produced solely by the
      oxidation of proline. Measurements of the respiratory quotient (RQ) confirmed
      that P. sinuata uses a combination of carbohydrates and proline to power its
      flight. At rest and during lift-generating tethered flight, the RQ is
      approximately 0.9. During warm-up, the RQ is significantly lower at 0.82, which
      is close to the theoretical value of 0.8 for the partial oxidation of proline.
      The rate of oxygen consumption during endothermic warm-up is 45 % of that during
      lift-generating tethered flight

PMID- 9556546
TI  - Myotomal slow muscle function of rainbow trout Oncorhynchus mykiss during steady
      swimming.
AB  - Strain and activity patterns were determined during slow steady swimming
      (tailbeat frequency 1.5-2.5 Hz) at three locations on the body in the slow
      myotomal muscle of rainbow trout Oncorhynchus mykiss using sonomicrometry and
      electromyography. Strain was independent of tailbeat frequency over the range
      studied and increased significantly from +/-3.3 % l0 at 0.35BL to +/-6 % at
      0.65BL, where l0 is muscle resting length and BL is total body length. Muscle
      activation occurred significantly later in the strain cycle at 0.35BL (phase
      shift 59 degrees) than at 0.65BL (30 degrees), and the duration of activity was
      significantly longer (211 degrees at 0.35BL and 181 degrees at 0.65BL). These
      results differ from those of previous studies. The results have been used to
      simulate in vivo activity in isolated muscle preparations using the work loop
      technique. Preparations from all three locations generated net positive power
      under in vivo conditions, but the negative power component increased from head to
      tail. Both kinematically, and in the way its muscle functions to generate
      hydrodynamic thrust, the rainbow trout appears to be intermediate between
      anguilliform swimmers such as the eel, which generate thrust along their entire
      body length, and carangiform fish (e.g. saithe Pollachius virens), which generate
      thrust primarily at the tail blade.

PMID- 9556547
TI  - Spatial vision in the prosobranch gastropod ampularia sp 
AB  - The eyes of gastropods of the genus Ampularia superficially resemble the well
      developed camera-type eyes of Littorina littorea and Strombus raninus. The eyes
      are of the closed-vesicle type, having a cornea and a lens that is separated from
      the retina by a narrow vitreous body. Light and electron microscopy were used to
      generate an accurate geometrical model of the Ampularia sp. eye, which was then
      used to predict its optical performance. The image quality of the lens was
      investigated using a modified microscope and revealed that images suffer from
      severe aberrations. The focal length was estimated to be approximately 430
      microm, putting the plane of best focus in or just proximal to the rhabdoms. The
      aberrant optics result in a large retinal blur-circle with a diameter of
      approximately 120 microm and an angular half-width of approximately 17 degrees,
      allowing only comparatively poor resolution compared with the eyes of Littorina
      littorea and Strombus raninus. Behavioural experiments revealed no significant
      optomotor response. The results imply that Ampularia sp. has poor spatial vision,
      limited by the blur-circles on the retina. The eyes appear to be suitable only
      for relatively simple visual tasks, such as finding an open water surface for
      breathing, but the large size of the eye allows it to perform this task even at
      night.

PMID- 9556548
TI  - Different effects of Gsalpha splice variants on beta2-adrenoreceptor-mediated
      signaling. The Beta2-adrenoreceptor coupled to the long splice variant of Gsalpha
      has properties of a constitutively active receptor.
AB  - The beta2-adrenoreceptor (beta2AR) couples to the G-protein Gs to mediate
      adenylyl cyclase activation. The splice variants of Gs alpha differ by a 15-amino
      acid insert between the Ras-like domain and the alpha-helical domain. The long
      splice variant of Gs alpha (Gs alphaL) binds GDP with lower affinity than the
      short splice variant (Gs alphaS), but the impact of this difference on the
      interaction of Gs alpha with the beta 2AR is not known. We studied the beta2
      AR/Gs alpha interaction using receptor/G-protein fusion proteins (beta2 AR Gs
      alphaS and beta2 AR Gs alphaL) expressed in Sf9 cells. Fusion of the beta2 AR to
      Gs alpha promotes efficient coupling as shown by high-affinity agonist binding
      and GTPase and adenylyl cyclase activation and ensures fixed stoichiometry
      between receptor and G-protein. Importantly, fusion does not change the
      fundamental properties of the beta2 AR or Gs alpha. The beta2 AR in beta2 AR Gs
      alphaL showed hallmarks of constitutive activity (increased potency and intrinsic
      activity of partial agonists, increased efficacy of inverse agonists, and
      increased basal GTPase activity) compared with the beta2 AR in beta2 AR Gs
      alphaS. The apparent constitutive activity of the beta2 AR in beta2 AR Gs alphaL
      may be due to the lower GDP affinity of Gs alphaL compared with Gs alphaS, i.e.
      Gs alphaL is more often nucleotide-free than Gs alphaS and, therefore, more
      frequently available to stabilize the beta2 AR in the active (R*) state. This
      study demonstrates that subtle structural differences between closely related G
      protein alpha-subunits can have important consequences for the functional
      properties of a G-protein-coupled receptor.

PMID- 9556549
TI  - Nonclassical protein sorting to the yeast vacuole.

PMID- 9556550
TI  - pICln binds to a mammalian homolog of a yeast protein involved in regulation of
      cell morphology.
AB  - Since its cloning and tentative identification as a chloride channel, the
      function of the pICln protein has been debated. Although there is no consensus
      regarding the specific function of pICln, it was suggested to play a role,
      directly or indirectly, in the function of a swelling-induced chloride
      conductance. Previously, the protein was shown to exist in several discrete
      protein complexes. To determine the function of the protein, we have begun the
      systematic identification of all proteins to which it binds. Here we show that
      four proteins firmly bind to pICln and identify the 72-kDa pICln-binding protein
      by affinity purification and peptide microsequencing. The interaction between
      this protein and pICln was verified several ways, including the extraction of
      several pICln clones from a cDNA library using the 72-kDa protein as a bait in a
      yeast two-hybrid screen. The protein is homologous to the yeast Skb1 protein.
      Skb1 interacts with Shk1, a homolog of the p21(Cdc42/Rac)-activated protein
      kinases (PAKs). The known involvement of PAKs in cytoskeletal rearrangement
      suggests that pICln may be linked to a system regulating cell morphology.

PMID- 9556551
TI  - Different subcellular distribution of caspase-3 and caspase-7 following Fas
      induced apoptosis in mouse liver.
AB  - Caspases plays a key role in the execution phase of apoptosis. "Initiator"
      caspases, such as caspase-8, activate "effector" caspases, such as caspase-3 and 
      7, which subsequently cleave cellular substrates thereby precipitating the
      dramatic morphological changes of apoptosis. Following treatment of mice with an
      agonistic anti-Fas antibody to induce massive hepatocyte apoptosis, we now
      demonstrate a distinct subcellular localization of the effector caspases-3 and 
      7. Active caspase-3 is confined primarily to the cytosol, whereas active caspase
      7 is associated almost exclusively with the mitochondrial and microsomal
      fractions. These data suggest that caspases-3 and -7 exert their primary
      functions in different cellular compartments and offer a possible explanation of
      the presence of caspase homologs with overlapping substrate specificities.
      Translocation and activation of caspase-7 to the endoplasmic reticulum correlates
      with the proteolytic cleavage of the endoplasmic reticular-specific substrate,
      sterol regulatory element-binding protein 1. Liver damage, induction of
      apoptosis, activation and translocation of caspase-7, and proteolysis of sterol
      regulatory element-binding protein 1 are all blocked by the caspase inhibitor,
      benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD. fmk). Our data
      demonstrate for the first time the differential subcellular compartmentalization
      of specific effector caspases following the induction of apoptosis in vivo.

PMID- 9556552
TI  - The peptidyl-prolyl isomerase domain of the CyP-40 cyclophilin homolog Cpr7 is
      not required to support growth or glucocorticoid receptor activity in
      Saccharomyces cerevisiae.
AB  - CyP-40 cyclophilins are found in association with molecular chaperone
      Hsp90.steroid receptor complexes. The amino-terminal portion of these
      cyclophilins harbors the characteristic peptidyl-prolyl isomerase (PPIase)
      domain, whereas three copies of the tetratricopeptide (TPR) motif, a structure
      shown to be involved in protein-protein interactions, and a putative calmodulin
      binding domain are located in the carboxyl-terminal half of the protein. The TPR
      domains mediate binding to Hsp90, but a requirement for the PPIase domain has not
      been established. To address this, we have investigated the effects of mutations
      that alter the PPIase domain of the Saccharomyces cerevisiae CyP-40 homolog,
      Cpr7. Because Cpr7 is required for rapid growth and full Hsp90 activity, a
      functional assessment of the PPIase domain could be performed in vivo. A mutation
      in the catalytic domain altering a conserved site predicted to be essential for
      isomerase activity did not compromise Cpr7 function. Furthermore, deletion of the
      entire PPIase domain did not significantly affect growth or Hsp90-mediated
      steroid receptor activity. These results indicate that the TPR-containing
      carboxyl terminus of Cpr7 is sufficient for fundamental Cpr7-dependent activity.

PMID- 9556553
TI  - Axin, a negative regulator of the wnt signaling pathway, directly interacts with
      adenomatous polyposis coli and regulates the stabilization of beta-catenin.
AB  - The regulators of G protein signaling (RGS) domain of Axin, a negative regulator
      of the Wnt signaling pathway, made a complex with full-length adenomatous
      polyposis coli (APC) in COS, 293, and L cells but not with truncated APC in SW480
      or DLD-1 cells. The RGS domain directly interacted with the region containing the
      20-amino acid repeats but not with that containing the 15-amino acid repeats of
      APC, although both regions are known to bind to beta-catenin. In the region
      containing seven 20-amino acid repeats, the region containing the latter five
      repeats bound to the RGS domain of Axin. Axin and beta-catenin simultaneously
      interacted with APC. Furthermore, Axin stimulated the degradation of beta-catenin
      in COS cells. Taken together with our recent observations that Axin directly
      interacts with glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin and
      that it promotes GSK-3beta-dependent phosphorylation of beta-catenin, these
      results suggest that Axin, APC, GSK-3beta, and beta-catenin make a tetrameric
      complex, resulting in the regulation of the stabilization of beta-catenin.

PMID- 9556554
TI  - Rpb3, stoichiometry and sequence determinants of the assembly into yeast RNA
      polymerase II in vivo.
AB  - Stoichiometry of the third largest subunit (Rpb3) of the yeast RNA polymerase II
      is a subject of continuing controversy. In this work we utilized immunoaffinity
      and nickel-chelate chromatographic techniques to isolate the RNA polymerase II
      species assembled in vivo in the presence of the His6-tagged and untagged Rpb3.
      The distribution pattern of tagged and untagged subunits among the RNA polymerase
      II molecules is consistent with a stoichiometry of 1 Rpb3 polypeptide per
      molecule of RNA polymerase. Deletion of either alpha-homology region (amino acids
      29-55 or 226-267) from the Rpb3 sequence abolished its ability to assemble into
      RNA polymerase II in vivo.

PMID- 9556555
TI  - Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates
      nuclear factor kappaB-mediated transactivations.
AB  - Steroid receptor coactivator-1 (SRC-1) specifically bound to the transcription
      factor NFkappaB subunit p50 but not to p65 as demonstrated by the yeast two
      hybrid tests and glutathione S-transferase pull down assays. The p50-binding site
      was localized to a subregion of SRC-1 (amino acids 759-1141) that encompasses the
      previously described CBP-p300-binding domain. In mammalian cells, SRC-1
      potentiated the NFkappaB-mediated transactivations in a dose-dependent manner.
      Coexpression of p300 further enhanced this SRC-1-potentiated level of
      transactivations, consistent with the recent findings in which CBP and p300 were
      shown to be transcription coactivators of the p65 subunit (Perkins, N. D.,
      Felzien, L. K., Betts, J. C., Leung, K., Beach, D. H., and Nabel, G. J. (1997)
      Science 275, 523-527; Gerritsen, M. E., Williams, A. J., Neish, A. S. , Moore,
      S., Shi, Y., and Collins, T. (1997) Proc. Acad. Natl. Sci. U. S. A. 94, 2927
      2932). These results suggest that at least two distinct coactivator molecules may
      cooperate to regulate the NFkappaB-dependent transactivations in vivo and SRC-1,
      originally identified as a coactivator for the nuclear receptors, may constitute
      a more widely used coactivation complex.

PMID- 9556556
TI  - Mammalian thioredoxin reductase is irreversibly inhibited by dinitrohalobenzenes
      by alkylation of both the redox active selenocysteine and its neighboring
      cysteine residue.
AB  - The immunostimulatory dinitrohalobenzene compound 1-chloro-2, 4-dinitrobenzene
      (DNCB) irreversibly inhibits mammalian thioredoxin reductase (TrxR) in the
      presence of NADPH, inducing an NADPH oxidase activity in the modified enzyme
      (Arner, E. S. J., Bjornstedt, M., and Holmgren, A. (1995) J. Biol. Chem. 270,
      3479-3482). Here we have further analyzed the reactivity with the enzyme of DNCB
      and analogues with varying immunomodulatory properties. We have also identified
      the reactive residues in bovine thioredoxin reductase, recently discovered to be
      a selenoprotein. We found that 4-vinylpyridine competed with DNCB for
      inactivation of TrxR, with DNCB being about 10 times more efficient, and only
      alkylation with DNCB but not with 4-vinylpyridine induced an NADPH oxidase
      activity. A number of nonsensitizing DNCB analogues neither inactivated the
      enzyme nor induced any NADPH oxidase activity. The NADPH oxidase activity of TrxR
      induced by dinitrohalobenzenes generated superoxide, as detected by reaction with
      epinephrine (the adrenochrome method). Addition of superoxide dismutase quenched
      this reaction and also stimulated the NADPH oxidase activity. By peptide analysis
      using mass spectrometry and Edman degradation, both the cysteine and the
      selenocysteine in the conserved carboxyl-terminal sequence Gly-Cys-Sec-Gly (where
      Sec indicates selenocysteine) were determined to be dinitrophenyl-alkylated upon
      incubation of native TrxR with NADPH and DNCB. A model for the interaction
      between TrxR and dinitrohalobenzenes is proposed, involving a functional FAD in
      the alkylated TrxR generating an anion nitroradical in a dinitrophenyl group,
      which in turn reacts with oxygen to generate superoxide. Production of reactive
      oxygen species and inhibited reduction of thioredoxin by the modified thioredoxin
      reductase after reaction with dinitrohalobenzenes may play a major role in the
      inflammatory reactions provoked by these compounds.

PMID- 9556557
TI  - The Trypanosoma cruzi mucin family is transcribed from hundreds of genes having
      hypervariable regions.
AB  - In previous works we have identified genes in the protozoan parasite Trypanosoma
      cruzi whose structure resemble those of mammalian mucin genes. Indirect evidence
      suggested that these genes might encode the core protein of parasite mucins,
      glycoproteins that were proposed to be involved in the interaction with, and
      invasion of, mammalian host cells. We now show that the mucin gene family from T.
      cruzi is much larger and diverse than expected. A minimal number of 484 mucin
      genes per haploid genome is calculated for a parasite clone. Most, if not all,
      genes are transcribed, as deduced from cDNA analysis. Comparison of the cDNA
      sequences showed evidences of a high mutation rate in localized regions of the
      genes. Sequence conservation among members of the family is much higher in the
      untranslated (UTR) regions than in the sequences encoding the mature mucin core
      protein. Transcription units can be classified into two main subfamilies
      according to the sequence homologies in the 5'-UTR, whereas the 3'-UTR is highly
      conserved in all clones analyzed. The common origin of members of this gene
      family as well as their relationships can be defined by sequence comparison of
      different domains in the transcription units. The regions encoding the N and C
      termini, supposed to correspond to the leader peptide and membrane-anchoring
      signal, respectively, (Di Noia, J. M., Sanchez, D. O., and Frasch, A. C. C.
      (1995) J. Biol. Chem. 270, 24146-24149) are highly conserved. Conversely, the
      central regions are highly variable. These regions encode the target sites for O
      glycosylation and are made of a variable number of repetitive units rich in Thr
      and Pro residues or are nonrepetitive but still rich in Thr/Ser and Pro residues.
      The region putatively coding for the N-terminal domain of the mature core protein
      is hypervariable, being different in most of the transcripts sequenced.
      Nonrepetitive central domains are unique to each gene. Gene-specific probes show
      that the relative abundance of different mRNAs varies greatly within the same
      parasite clone.

PMID- 9556558
TI  - Inhibitor binding within the NarI subunit (cytochrome bnr) of Escherichia coli
      nitrate reductase A.
AB  - We have used inhibitors and site-directed mutants to investigate quinol binding
      to the cytochrome bnr (NarI) of Escherichia coli nitrate reductase (NarGHI). Both
      stigmatellin and 2-n-heptyl-4-hydroxyquinoline-N-oxide (HOQNO) inhibit
      menadiol:nitrate oxidoreductase activity with I50 values of 0.25 and 6 microM,
      respectively, and prevent the generation of a NarGHI-dependent proton
      electrochemical potential across the cytoplasmic membrane. These inhibitors have
      little effect on the rate of reduction of the two hemes of NarI (bL and bH), but
      have an inhibitory effect on the extent of nitrate-dependent heme reoxidation. No
      quinol-dependent heme bH reduction is detected in a mutant lacking heme bL (NarI
      H66Y), whereas a slow but complete heme bL reduction is detected in a mutant
      lacking heme bH (NarI-H56R). This is consistent with physiological quinol binding
      and oxidation occurring at a site (QP) associated with heme bL which is located
      toward the periplasmic side of NarI. Optical and EPR spectroscopies performed in
      the presence of stigmatellin or HOQNO provide further evidence that these
      inhibitors bind at a heme bL-associated QP site. These results suggest a model
      for electron transfer through NarGHI that involves quinol binding and oxidation
      in the vicinity of heme bL and electron transfer through heme bH to the
      cytoplasmically localized membrane-extrinsic catalytic NarGH dimer.

PMID- 9556559
TI  - Peroxynitrite increases the degradation of aconitase and other cellular proteins
      by proteasome.
AB  - We report that exposure of aconitase to moderate concentrations of peroxynitrite,
      3-morpholinosydnonimine (SIN-1; a superoxide- and nitric oxide-liberating
      substance), or hydrogen peroxide, inhibits the enzyme and enhances susceptibility
      to proteolytic digestion by the isolated 20 S proteasome. Exposure to more severe
      levels of oxidative stress, from these same agents, causes further inhibition of
      the enzymatic activity of aconitase but actually decreases its proteolytic
      breakdown by proteasome. It should be noted that the superoxide and nitric oxide
      liberated by SIN-1 decomposition react to form a steady flux of peroxynitrite. S
      Nitroso-N-acetylpenicillamine, a compound that liberates nitric oxide alone,
      causes only a small loss of aconitase activity (25% or less) and has no effect on
      the proteolytic susceptibility of the enzyme. Proteasome also seems to be the
      main protease in cell lysates that can degrade aconitase after it has been
      oxidatively modified by exposure to peroxynitrite, SIN-1, or hydrogen peroxide.
      Using cell lysates isolated from K562 cells treated for several days with an
      antisense oligodeoxynucleotide to the initiation codon region of the C2 subunit
      of proteasome (a treatment which diminishes proteasome activity by 50-60%), the
      enhanced degradation of moderately damaged aconitase was essentially abolished.
      Other model proteins as well as complex mixtures of proteins, such as cell
      lysates, also exhibit enhanced proteolytic susceptibility after moderate SIN-1
      treatment. Therefore we conclude that peroxynitrite reacts readily with proteins
      and that mild modification by peroxynitrite results in selective recognition and
      degradation by proteasome.

PMID- 9556560
TI  - Reaction of O6-benzylguanine-resistant mutants of human O6-alkylguanine-DNA
      alkyltransferase with O6-benzylguanine in oligodeoxyribonucleotides.
AB  - Inactivation of the human DNA repair protein, O6-alkylguanine-DNA
      alkyltransferase (AGT), by O6-benzylguanine renders tumor cells susceptible to
      killing by alkylating agents. AGT mutants resistant to O6-benzylguanine can be
      made by converting Pro140 to an alanine (P140A) or Gly156 to an alanine (G156A).
      These mutations had a much smaller effect on the reaction with O6-benzylguanine
      when it was incorporated into a short single-stranded oligodeoxyribonucleotide.
      Such oligodeoxyribonucleotides could form the basis for the design of improved
      AGT inhibitors. AGT and mutants P140A and G156A preferentially reacted with O6
      benzylguanine when incubated with a mixture of two 16-mer
      oligodeoxyribonucleotides, one containing O6-benzylguanine and the other, O6
      methylguanine. When the 6 amino acids located in positions 159-164 in AGT were
      replaced by the equivalent sequence from the Escherichia coli Ada-C protein
      (mutant AGT/6ada) the preference for benzyl repair was eliminated. Further
      mutation incorporating the P140A change into AGT/6ada giving mutant P140A/6ada
      led to a protein that resembled Ada-C in preference for the repair of methyl
      groups, but P140A/6ada did not differ from P140A in reaction with the free base
      O6-benzylguanine. Changes in the AGT active site pocket can therefore affect the
      preference for repair of O6-benzyl or -methyl groups when present in an
      oligodeoxyribonucleotide without altering the reaction with free O6
      benzylguanine.

PMID- 9556561
TI  - Gar1p binds to the small nucleolar RNAs snR10 and snR30 in vitro through a
      nontypical RNA binding element.
AB  - The nucleolar proteins Gar1p and fibrillarin possess a typical nucleolar
      glycine/arginine-rich domain and belong to ribonucleoprotein particles. Both
      proteins are essential for yeast cell growth and are required for pre-rRNA
      processing. In addition, Gar1p is involved in pre-rRNA pseudouridylation, whereas
      fibrillarin is required for pre-rRNA methylation. Gar1p and fibrillarin are each
      associated with a different subset of the small nucleolar RNAs (snoRNAs). Gar1p
      is co-immunoprecipitated with the H/ACA family of snoRNAs, whereas fibrillarin is
      co-immunoprecipitated with the C/D family. However, attempts to demonstrate
      direct interactions between fibrillarin and snoRNAs have failed, and such
      interactions between Gar1p and the H/ACA snoRNAs had not yet been reported. Among
      the H/ACA snoRNAs associated with Gar1p, one can distinguish a large group of
      snoRNAs that are not essential in yeast and serve as guides for pseudouridine
      synthesis onto the pre-rRNA molecule. In contrast, the two snoRNAs snR10 and
      snR30 are required for normal cell growth and for pre-rRNA cleavage. We show here
      that Gar1p interacts in vitro directly and specifically with these two snoRNAs.
      Deletion analysis of Gar1p indicates that a major RNA binding element, which is
      extremely well conserved throughout evolution, lies in the middle of the protein.
      However, this domain alone binds poorly to the target RNAs and an accessory
      domain is required to restore efficient binding. The accessory domain can be
      either one of the glycine/arginine-rich domains or a second element of the core
      of the protein that is highly conserved between different species.

PMID- 9556562
TI  - Preparation of MUC-1 oligomers using an improved convergent solid-phase peptide
      synthesis.
AB  - The sequentially repeating nature of the core mucin polypeptide chain MUC-1 on
      the surface of malignant cells makes it an excellent target for cancer
      immunotherapy. We describe a reliable and efficient method of synthesizing
      oligomers, up to five tandem repeats and oligomer heterotope derivatives with a
      15-amino acid epitope from tetanus toxin using an improved convergent solid-phase
      peptide synthesis. The different oligomers were easily distinguishable by reverse
      phase high pressure liquid chromatography, but they were poorly fixed and
      migrated with the same migration rate, irrespective of size, in electrophoretic
      studies. In contrast, the oligomer heterotopes exhibited size-dependent
      electrophoretic behavior but in high pressure liquid chromatography chromatograms
      the different heterotopes were eluted simultaneously in two peaks representing
      the L- and D-enantiomers of the derivatives. The oligomer heterotopes were
      recognized as antigens in Western blotting with a murine monoclonal antibody
      against the epitope APDTR. In enzyme immunoassay studies with the same antibody
      an increasing reactivity was observed against the larger oligomers and confirmed
      by inhibition assays as the MUC-1 pentamer was the most efficient inhibitor.
      These results support the suggestion that the pentamer attains a structure closer
      to the native conformation and is more immunogenic. In conclusion, large
      composite peptides can be reliably synthesized with the convergent solid-phase
      peptide strategy offering an attractive option to vaccine designing and
      development.

PMID- 9556563
TI  - Ciao 1 is a novel WD40 protein that interacts with the tumor suppressor protein
      WT1.
AB  - The Wilms tumor suppressor protein, WT1, is a transcription factor capable of
      activating or repressing transcription of various cellular genes. The mechanisms
      involved in regulating the transcriptional activities of WT1 are beginning to be
      unraveled. It appears that physical interactions of other cellular proteins (p53
      and par-4) with WT1 can modulate the function of WT1. Here, we report the
      identification and cloning of a novel WT1-interacting protein termed Ciao 1, a
      member of the WD40 family of proteins. Ciao 1 specifically interacts with WT1
      both in vitro and in vivo. This interaction alters the mobility of a WT1.DNA
      complex in gel shift assays, and results in a decrease in transcriptional
      activation mediated by WT1. Ciao 1 does not inhibit binding of WT1 to its
      consensus nucleotide sequence and does not affect the repression activity of WT1.
      Thus, Ciao 1 appears to specifically modulate the transactivation activity of WT1
      and may function to regulate the physiological functions of WT1 in cell growth
      and differentiation.

PMID- 9556564
TI  - Sulfuryl transfer: the catalytic mechanism of human estrogen sulfotransferase.
AB  - Estrogen sulfotransferase (EST) catalyzes the transfer of the sulfuryl group from
      3'-phosphoadenosine 5'-phosphosulfate (PAPS) to 17beta-estradiol (E2). The
      sulfation of E2 prevents it from binding to, and thereby activating, the estrogen
      receptor. The regulation of EST appears to be causally linked to tumorigenesis in
      the breast and endometrium. In this study, recombinant human EST is
      characterized, and the catalytic mechanism of the transfer reaction is
      investigated in ligand binding and initial rate experiments. The native enzyme is
      a dimer of 35-kDa subunits. The apparent equilibrium constant for transfer to E2
      is (4.5 +/- 0.2) x 10(3) at pH 6.3 and T = 25 +/- 2 degrees C. Initial rate
      studies provide the kinetic constants for the reaction and suggest a sequential
      mechanism. E2 is a partial substrate inhibitor (Ki = 80 +/- 5 nM). The binding of
      two E2 per EST subunit suggests that the partial inhibition occurs through
      binding at an allosteric site. In addition to providing the dissociation
      constants for the ligand-enzyme complexes, binding studies demonstrate that each
      substrate binds independently to the enzyme and that both the E.PAP.E2S and
      E.PAP.E2 dead-end complexes form. These results strongly suggest a Random Bi Bi
      mechanism with two dead-end complexes.

PMID- 9556565
TI  - Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in
      isolated perfused rat heart.
AB  - The metabolism of 4-hydroxy-trans-2-nonenal (HNE), an alpha, beta-unsaturated
      aldehyde generated during lipid peroxidation, was studied in isolated perfused
      rat hearts. High performance liquid chromatography separation of radioactive
      metabolites recovered from [3H]HNE-treated hearts revealed four major peaks.
      Based on the retention times of synthesized standards, peak I, which accounted
      for 20% radioactivity administered to the heart, was identified to be due to
      glutathione conjugates of HNE. Peaks II and III, containing 2 and 37%
      radioactivity, were assigned to 1, 4-dihydroxy-2-nonene (DHN) and 4-hydroxy-2
      nonenoic acid, respectively. Peak IV was due to unmetabolized HNE. The
      electrospray ionization mass spectrum of peak I revealed two prominent
      metabolites with m/z values corresponding to [M + H]+ of HNE and DHN conjugates
      with glutathione. The presence of 4-hydroxy-2-nonenoic acid in peak III was
      substantiated using gas chromatography-chemical ionization mass spectroscopy.
      When exposed to sorbinil, an inhibitor of aldose reductase, no GS-DHN was
      recovered in the coronary effluent, and treatment with cyanamide, an inhibitor of
      aldehyde dehydrogenase, attenuated 4-hydroxy-2-nonenoic acid formation. These
      results show that the major metabolic transformations of HNE in rat heart involve
      conjugation with glutathione and oxidation to 4-hydroxy-2-nonenoic acid. Further
      metabolism of the GS-HNE conjugate involves aldose reductase-mediated reduction,
      a reaction catalyzed in vitro by homogenous cardiac aldose reductase.

PMID- 9556566
TI  - A negative vitamin D response DNA element in the human parathyroid hormone
      related peptide gene binds to vitamin D receptor along with Ku antigen to mediate
      negative gene regulation by vitamin D.
AB  - We found that the human parathyroid hormone-related peptide (hPTHrP) gene
      contained a DNA element (nVDREhPTHrP) homologous to a negative vitamin D response
      element in the human parathyroid hormone gene. It bound to vitamin D receptor
      (VDR) but not retinoic acid Xalpha receptor (RXRalpha) in the human T cell line
      MT2 cells. VDR binding to this element was confirmed by the Southwestern assay
      combined with immunodepletion using anti-VDR monoclonal antibody, and this
      binding activity was repressed by 1,25-dihydroxyvitamin D3. Such a repression was
      reversed by acid phosphatase treatment, suggesting that 1,25-dihydroxyvitamin D3
      phosphorylates VDR to weaken its binding activity to nVDREhPTHrP. In
      electrophoretic mobility shift assay, we found anti-Ku antigen antibody
      specifically supershifted the MT2 nuclear proteinnVDREhPTHrP complex. The
      nVDREhPTHrP-bearing reporter plasmid produced vitamin D-dependent inhibition of
      the reporter activity in MT2 cells, which was markedly masked by the introduction
      of the Ku antigen expression vector in the antisense orientation. On the other
      hand, such a procedure did not perturb the vitamin D response element-mediated
      gene stimulation by vitamin D. These results indicate that nVDREhPTHrP interacts
      with Ku antigen in addition to VDR to mediate gene suppression by vitamin D.

PMID- 9556567
TI  - Functional characterization of the Tn5 transposase by limited proteolysis.
AB  - The 476 amino acid Tn5 transposase catalyzes DNA cutting and joining reactions
      that cleave the Tn5 transposon from donor DNA and integrate it into a target
      site. Protein-DNA and protein-protein interactions are important for this
      tranposition process. A truncated transposase variant, the inhibitor, decreases
      transposition rates via the formation of nonproductive complexes with
      transposase. Here, the inhibitor and the transposase are shown to have similar
      secondary and tertiary folding. Using limited proteolysis, the transposase has
      been examined structurally and functionally. A DNA binding region was localized
      to the N-terminal 113 amino acids. Generally, the N terminus of transposase is
      sensitive to proteolysis but can be protected by DNA. Two regions are predicted
      to contain determinants for protein-protein interactions, encompassing residues
      114-314 and 441-476. The dimerization regions appear to be distinct and may have
      separate functions, one involved in synaptic complex formation and one involved
      in nonproductive multimerization. Furthermore, predicted catalytic regions are
      shown to lie between major areas of proteolysis.

PMID- 9556568
TI  - Regulation of syndecan-4 phosphorylation in vivo.
AB  - Recent studies suggest that some of the heparan sulfate-carrying proteoglycans
      may directly participate in signaling via their cytoplasmic tail. The present
      investigation addresses the potential involvement of syndecan-4, a widely
      expressed transmembrane proteoglycan, in this process. We found that the
      cytoplasmic tail of syndecan-4 is phosphorylated on a single serine residue
      (Ser183) in growth-arrested NIH 3T3 fibroblasts, with a stoichiometry of 0.3 mol
      Pi/mol syndecan-4. Treatment of the cells with a protein kinase C (PKC)
      activating phorbol ester lead to a 2.5-fold increase in Ser183 phosphorylation.
      This increase was inhibited by a generic PKC inhibitor but not by an inhibitor
      specific to the calcium-dependent conventional PKCs, suggesting that the
      cytoplasmic tail of syndecan-4 is phosphorylated by a calcium-independent novel
      PKC isozyme. Application of 10-30 ng/ml basic fibroblast growth factor (bFGF)
      produced a 2-3-fold reduction in the phosphorylation of syndecan-4. Because
      treatment with the phosphatase inhibitor calyculin prevented the bFGF-induced
      decrease in syndecan-4 phosphorylation, the effect of bFGF appears to be mediated
      by a protein serine/threonine phosphatase type 1 or 2A. We conclude that the
      cytoplasmic tail of syndecan-4 is subject to in vivo phosphorylation on Ser183,
      which is regulated by the activities of a novel PKC isozyme and a bFGF-dependent
      serine/threonine phosphatase.

PMID- 9556569
TI  - The heparan sulfate binding sequence of interferon-gamma increased the on rate of
      the interferon-gamma-interferon-gamma receptor complex formation.
AB  - Interferon-gamma (IFNgamma), in common with a number of growth factors, binds
      both to heparan sulfate or heparin-related molecules and to a specific high
      affinity receptor (IFNgammaR). Using surface plasmon resonance technology,
      kinetic analysis of the IFNgamma. IFNgammaR complex formation was performed with
      the extracellular part of IFNgammaR immobilized on a sensor chip. At the sensor
      chip surface, IFNgamma was bound by two IFNgammaR molecules with an affinity in
      the nanomolar range (0.68 nM). This binding was characterized by an important on
      rate, kon = 7.3 x 10(6) M-1.s-1, and an off rate, koff = 5 x 10(-3).s-1. This
      binding assay was used to investigate a possible role of heparin in the
      IFNgamma.IFNgammaR complex formation. In contrast to growth factors for which
      binding to heparin is usually required for high affinity receptor interaction, we
      found in this study that IFNgamma bound to heparin displayed a strongly reduced
      affinity for its receptor. This is consistent with the fact that a cluster of
      basic amino acids (KTGKRKR, called the C1 domain) in the carboxyl-terminal
      sequence of the cytokine was involved both in heparin and receptor recognition.
      To understand how a single domain of IFNgamma could be implicated in two discrete
      functions (i.e. binding to heparin and to IFNgammaR), we also analyzed in a
      detailed manner the role of the IFNgamma carboxyl-terminal sequence in receptor
      binding. Using forms of IFNgamma, with carboxyl terminus truncations of defined
      regions of the heparin binding sequence, we found that the C1 domain functioned
      by increasing the on rate of the IFNgamma.IFNgammaR binding reaction but was not
      otherwise required for the stability of the complex. Interactions between the
      IFNgamma carboxyl-terminal domain and IFNgammaR could increased the association
      rate of the reaction either by increasing the number of encounters between the
      two molecules or by favoring productive collisions. The mechanisms by which
      heparan sulfate regulates IFNgamma activity may thus include both control of
      selective protease cleavage events, which directly affect the cytokine activity,
      and also an ability to modulate the interaction of IFNgamma with the IFNgammaR
      via competitive binding to the C1 domain.

PMID- 9556570
TI  - Phosphorylation of thyroid hormone receptors by protein kinase A regulates DNA
      recognition by specific inhibition of receptor monomer binding.
AB  - Thyroid hormone receptor (T3R) alpha-1 and its oncogenic derivative, the v-ERB A
      protein, are phosphorylated by cAMP-dependent protein kinase A. Although this
      phosphorylation appears to be necessary for the oncogenic properties of v-ERB A,
      the mechanism by which phosphorylation influences the functions of v-ERB A and of
      the normal T3R has not been established. The protein kinase A phosphorylation
      site in T3Ralpha-1 is within a domain that is known to contribute to the DNA
      recognition properties of these receptors. We therefore analyzed the effects of
      protein kinase A phosphorylation on DNA recognition by the normal T3Ralpha and by
      the v-ERB A oncoprotein. We report here that phosphorylation of these receptor
      derivatives does not significantly alter the overall affinity of receptor dimers
      for DNA. However, phosphorylation does notably alter DNA recognition by
      preventing, or greatly inhibiting, the ability of these receptors to bind to DNA
      as protein monomers. These studies suggest that the phosphorylation of T3Ralpha-1
      and v-ERB A by protein kinase A may provide a means of altering promoter
      recognition through a post-translational modification.

PMID- 9556571
TI  - Mutagenesis of beta-Glu-195 of the Rhodospirillum rubrum F1-ATPase and its role
      in divalent cation-dependent catalysis.
AB  - We introduced mutations at the fully conserved residue Glu-195 in subunit beta of
      Rhodospirillum rubrum F1-ATPase. The activities of the expressed wild type (WT)
      and mutant beta subunits were assayed by following their capacity to assemble
      into the earlier prepared beta-depleted, membrane-bound R. rubrum enzyme
      (Philosoph, S., Binder, A., and Gromet-Elhanan, Z. (1977) J. Biol. Chem. 252,
      8742-8747) and to restore ATP synthesis and/or hydrolysis activity. All three
      mutations, beta-E195K, beta-E195Q, and beta-E195G, were found to bind as the
      WTbeta into the beta-depleted enzyme. They restored between 30 and 60% of the WT
      restored photophosphorylation activity and 16, 45, and 105%, respectively of the
      CaATPase activity. The mutants required, however, much higher concentrations of
      divalent cations and could not restore any significant MgATPase or MnATPase
      activities. Only beta-E195G could restore some of these activities when assayed
      in the presence of 100 mM sulfite and high MgCl2 or MnCl2 concentrations. These
      results suggest that the observed difference in restoration of ATP synthesis and
      CaATPase, as compared with MgATPase and MnATPase, can be due to the tight
      regulation of the last two activities, resulting in their inhibition at
      cation/ATP ratios above 0.5. The R. rubrum F1beta-E195 is equivalent to the
      mitochondrial F1beta-E199, which points into the tunnel leading to the F1
      catalytic nucleotide binding sites (Abrahams, J. P., Leslie, A. G. W., Lutter,
      R., and Walker, J. E. (1994) Nature 370, 621-628). Our findings indicate that
      this residue, although not an integral part of the F1 catalytic sites, affects
      divalent cation binding and release of inhibitory MgADP, suggesting its
      participation in the interconversion of the F1 catalytic sites between different
      conformational states.

PMID- 9556572
TI  - Identification and characterization of a novel 9.2-kDa membrane sector-associated
      protein of vacuolar proton-ATPase from chromaffin granules.
AB  - Vacuolar proton-translocating ATPase (holoATPase and free membrane sector) was
      isolated from bovine chromaffin granules by blue native polyacrylamide gel
      electrophoresis. A 5-fold excess of membrane sector over holoenzyme was
      determined in isolated chromaffin granule membranes. M9.2, a novel extremely
      hydrophobic 9.2-kDa protein comprising 80 amino acids, was detected in the
      membrane sector. It shows sequence and structural similarity to Vma21p, a yeast
      protein required for assembly of vacuolar ATPase. A second membrane sector
      associated protein (M8-9) was identified and characterized by amino-terminal
      protein sequencing.

PMID- 9556573
TI  - Regulation of peroxisome proliferator-activated receptor alpha-induced
      transactivation by the nuclear orphan receptor TAK1/TR4.
AB  - Recently, we reported the cloning of the nuclear orphan receptor TAK1. In this
      study, we characterized the sequence requirements for optimal TAK1 binding and
      analyzed the repression of the peroxisome proliferator-activated receptor alpha
      (PPARalpha) signaling pathway by TAK1. Site selection analysis showed that TAK1
      has the greatest affinity for direct repeat-1 response elements (RE) containing
      AGGTCAAAGGTCA (TAK1-RE) to which it binds as a homodimer. TAK1 is a very weak
      inducer of TAK1-RE-dependent transcriptional activation. We observed that TAK1,
      as PPARalpha, is expressed within rat hepatocytes and is able to bind the
      peroxisome proliferator response elements (PPREs) present in the promoter of the
      PPARalpha target genes rat enoyl-CoA hydratase (HD) and peroxisomal fatty acyl
      CoA oxidase (ACOX). TAK1 is unable to induce PPRE-dependent transcriptional
      activation and represses PPARalpha-mediated transactivation through these
      elements in a dose-dependent manner. Two-hybrid analysis showed that TAK1 does
      not form heterodimers with either PPARalpha or retinoid X receptor (RXRalpha),
      indicating that this repression does not involve a mechanism by which TAK1
      titrates out PPARalpha or RXRalpha from PPAR.RXR complexes. Further studies
      demonstrated that the PPARalpha ligand 8(S)-hydroxyeicosatetraenoic acid strongly
      promotes the interaction of PPARalpha with the co-activator RIP-140 but decreases
      the interaction of PPARalpha with the co-repressor SMRT. In contrast, TAK1
      interacts with RIP-140 but not with SMRT and competes with PPARalpha for RIP-140
      binding. These observations indicated that the antagonistic effects of TAK1 on
      PPARalpha.RXRalpha transactivation act at least at two levels in the PPARalpha
      signaling pathway: competition of TAK1 with PPARalpha.RXR for binding to PPREs as
      well as to common co-activators, such as RIP-140. Our results suggest an
      important role for TAK1 in modulating PPARalpha-controlled gene expression in
      hepatocytes.

PMID- 9556574
TI  - Identification of pairwise interactions in the alpha-neurotoxin-nicotinic
      acetylcholine receptor complex through double mutant cycles.
AB  - alpha-Neurotoxins are potent inhibitors of the nicotinic acetylcholine receptor
      (nAChR), binding with high affinity to the two agonist sites located on the
      extracellular domain. Previous site-directed mutagenesis had identified three
      residues on the alpha-neurotoxin from Naja mossambica mossambica (Lys27, Arg33,
      and Lys47) and four residues on the mouse muscle nAChR alpha-subunit (Val188,
      Tyr190, Pro197, and Asp200) as contributing to binding. In this study,
      thermodynamic mutant cycle analysis was applied to these sets of residues to
      identify specific pairwise interactions. Amino acid variants of alpha-neurotoxin
      from N. mossambica mossambica at position 33 and of the nAChR at position 188
      showed strong energetic couplings of 2-3 kcal/mol at both binding sites.
      Consistently smaller yet significant linkages of 1.6-2.1 kcal/mol were also
      observed between variants at position 27 on the toxin and position 188 on the
      receptor. Additionally, toxin residue 27 coupled to the receptor residues 190,
      197, and 200 at the alphadelta binding site with observed coupling energies of
      1.5-1.9 kcal/mol. No linkages were found between toxin residue Lys47 and the
      receptor residues studied here. These results provide direct evidence that the
      two conserved cationic residues Arg33 and Lys27, located on loop II of the toxin
      structure, are binding in close proximity to the alpha-subunit region between
      residues 188-200. The toxin residue Arg33 is closer to Val188, where it is likely
      stabilized by adjacent negative or aromatic residues on the receptor structure.
      Lys27 is positioned closer to Tyr190, Pro197, and Asp200, where it is likely
      stabilized through electrostatic interaction with Asp200 and/or cation/pi
      interactions with Tyr190.

PMID- 9556575
TI  - Immunological detection of conformational neoepitopes associated with the serpin
      activity of plasminogen activator inhibitor type-2.
AB  - The physiological roles of plasminogen activator inhibitor-2 (PAI-2) are not yet
      well understood. Kinetic studies suggest a role in the regulation of plasminogen
      activator-driven proteolysis in many cell types. This study describes a
      monoclonal antibody (2H5), which uniquely recognizes neoepitope determinants on
      PAI-2 appearing after thermodynamic relaxation of the molecule. Enzyme-linked
      immunosorbent assays and native polyacrylamide gel electrophoresis immunoblotting
      confirmed the specificity of 2H5 for urokinase type plasminogen activator.PAI-2
      complexes. Examination of the affinity of 2H5 for complexes formed between PAI-2
      and a synthetic 14-mer reactive site loop peptide, PAI-2 treated with tissue
      plasminogen activator, or thrombin suggests that the 2H5 epitope is determined
      exclusively by sequences found only on PAI-2 following proteolytic cleavage of
      the Arg380-Thr381 bond and insertion of the reactive site loop into beta-sheet A.
      Peptides lacking both the P13 (Glu368) and P14 (Thr367) residues did not induce a
      conformational change or affect the inhibitory activity of PAI-2, indicating that
      one or both of these residues are critical for PAI-2 function. To our knowledge,
      this is the first description of a monoclonal antibody that can distinguish
      conformational changes in PAI-2 related specifically to its potential biological
      function(s).

PMID- 9556576
TI  - The p53 tumor suppressor inhibits transcription of the TATA-less mouse DP1
      promoter.
AB  - Cell cycle progression is subject to several regulatory controls, of which the
      p53 protein plays a major role in growth arrest, subsequent to the detection of
      cellular aberrations. It is well documented that p53 has the ability to inhibit
      transcription driven by several promoters, possibly via distinct mechanisms. In
      this report, we show that expression of the cell cycle regulatory transcription
      factor DP1 is strongly inhibited by p53, at the level of transcription and
      probably through the basal TATA-less promoter. This inhibitory activity has a
      relative specificity for the DP1 promoter compared with the functionally related
      E2F1 promoter or unrelated promoters such as those of the transcription factor
      ATFa or the thymidine kinase gene. Inhibition of DP1 transcription has
      implications in one of the several possible mechanisms through which p53 induces
      cell cycle arrest.

PMID- 9556577
TI  - Bruton's tyrosine kinase-mediated interleukin-2 gene activation in mast cells.
      Dependence on the c-Jun N-terminal kinase activation pathway.
AB  - Cross-linking of the high affinity IgE receptor (FcepsilonRI) on mast cells
      induces secretion of cytokines, including interleukin (IL)-2, through
      transcriptional activation of cytokine genes. Previously, defects in the gene
      coding for Bruton's tyrosine kinase (Btk) were shown to result in defective
      cytokine production in mast cells, and thereby mice carrying btk mutations
      exhibited diminished anaphylactic reactions in response to IgE and antigen. In
      this study, we provide evidence that the transcription factors involved in the IL
      2 gene expression in T cells are also required for maximal activation of the IL-2
      gene in FcepsilonRI-stimulated mast cells. Among them, AP-1 (Jun/Fos) and NF-AT
      were identified as candidate transcription factors that are regulated by Btk.
      Consistent with our previous data indicating that Btk regulates stress-activated
      protein kinases, c-Jun N-terminal kinase (JNK), c-Jun and other JNK-regulatable
      transcription factors are activated by FcepsilonRI cross-linking in a Btk
      dependent manner. Further, FcepsilonRI-induced IL-2 gene activation is dependent
      on c-Jun and a component, SEK1, of its upstream activation pathway. Collectively,
      these data demonstrate that Btk regulates the transcription of the IL-2 gene
      through the JNK-regulatable transcription factors in FcepsilonRI-stimulated mast
      cells.

PMID- 9556578
TI  - Force required to break alpha5beta1 integrin-fibronectin bonds in intact adherent
      cells is sensitive to integrin activation state.
AB  - Binding of integrin receptors to extracellular ligands is a complex process
      involving receptor-ligand interactions at the cell-substrate interface, signals
      activating the receptors, and assembly of cytoskeletal and adhesion plaque
      proteins at the cytoplasmic face. To analyze the contribution of these elements
      to overall cell adhesion, we have developed a model system that characterizes the
      functional binding characteristic for adhesion receptors as the force required to
      separate the integrin-ligand bond. A spinning disk device was used to apply a
      range of controlled hydrodynamic forces to adherent cells. The adhesion of K562
      erythroleukemia cells, a cell line expressing a single fibronectin receptor,
      integrin alpha5beta1, which was uniformly activated with the monoclonal antibody
      TS2/16, to defined fibronectin surface densities was examined. Cell adhesion
      strength increased linearly with receptor and ligand densities. Based on chemical
      equilibrium principles, it is shown that adhesion strength is directly
      proportional to the number of receptor-ligand bonds. This analysis provides for
      the definition of a new physical parameter, the adhesion constant psi, which is
      related to the bond strength and binding equilibrium constant and has units of
      force-length2. This parameter can be measured by the experimental system
      presented and is governed by the activation state of integrin receptors. This
      simplified model isolates the integrin receptor-ligand binding parameters and
      provides a basis for analysis of the functions of signaling and cytoskeletal
      elements in the adhesion process.

PMID- 9556579
TI  - Site-directed mutations in the vnd/NK-2 homeodomain. Basis of variations in
      structure and sequence-specific DNA binding.
AB  - Secondary structures, DNA binding properties, and thermal denaturation behavior
      of six site-directed mutant homeodomains encoded by the vnd/NK-2 gene from
      Drosophila melanogaster are described. Three single site H52R, Y54M, and T56W
      mutations, two double site H52R/T56W and Y54M/T56W mutations, and one triple site
      H52R/Y54M/T56W mutation were investigated. These positions were chosen based on
      their variability across homeodomains displaying differences in secondary
      structure and DNA binding specificity. Multidimensional NMR, electrophoretic
      mobility shift assays, and circular dichroism spectropolarimetry studies were
      carried out on recombinant 80-amino acid residue proteins containing the
      homeodomain. Position 56, but more importantly position 56 in combination with
      position 52, plays an important role in determining the length of the recognition
      helix. The H52R mutation alone does not affect the length of this helix but does
      increase the thermal stability. Introduction of site mutations at positions 52
      and 56 in vnd/NK-2 does not modify their high affinity binding to the 18-base
      pair DNA fragment containing the vnd/NK-2 consensus binding sequence, CAAGTG.
      Site mutations involving position 54 (Y54M, Y54M/T56W, and H52R/Y54M/T56W) all
      show a decrease of 1 order of magnitude in their binding affinity. The roles in
      structure and sequence specificity of individual atom-atom interactions are
      described.

PMID- 9556580
TI  - Identification of residues in the neuronal alpha7 acetylcholine receptor that
      confer selectivity for conotoxin ImI.
AB  - To identify residues in the neuronal alpha7 acetylcholine subunit that confer
      high affinity for the neuronal-specific toxin conotoxin ImI (CTx ImI), we
      constructed alpha7-alpha1 chimeras containing segments of the muscle alpha1
      subunit inserted into equivalent positions of the neuronal alpha7 subunit. To
      achieve high expression in 293 human embryonic kidney cells and formation of homo
      oligomers, we joined the extracellular domains of each chimera to the M1 junction
      of the 5-hydroxytryptamine-3 (5HT-3) subunit. Measurements of CTx ImI binding to
      the chimeric receptors reveal three pairs of residues in equivalent positions of
      the primary sequence that confer high affinity of CTx ImI for alpha7/5HT-3 over
      alpha1/5HT-3 homo-oligomers. Two of these pairs, alpha7Trp55/alpha1Arg55 and
      alpha7Ser59/alpha1Gln59, are within one of the four loops that contribute to the
      traditional non-alpha subunit face of the muscle receptor binding site. The third
      pair, alpha7Thr77/alpha1Lys77, is not within previously described loops of either
      the alpha or non-alpha faces and may represent a new loop or an allosterically
      coupled loop. Exchanging these residues between alpha1 and alpha7 subunits
      exchanges the affinities of the binding sites for CTx ImI, suggesting that the
      alpha7 and alpha1 subunits, despite sequence identity of only 38%, share similar
      protein scaffolds.

PMID- 9556581
TI  - Structural elements in alpha-conotoxin ImI essential for binding to neuronal
      alpha7 receptors.
AB  - The neuronal-specific toxin alpha-conotoxin ImI (CTx ImI) has the sequence Gly
      Cys-Cys-Ser-Asp-Pro-Arg-Cys-Ala-Trp-Arg-Cys-NH2, in which each cysteine forms a
      disulfide bridge to produce a constrained two-loop structure. To investigate the
      structural basis for bioactivity we mutated individual residues in CTx ImI and
      determined bioactivity. Bioactivity of the toxins was determined by their
      competition against 125I-labeled alpha-bungarotoxin binding to homomeric
      receptors containing alpha7 sequence in the major extracellular domain and 5HT-3
      sequence elsewhere. The results reveal two regions in CTx ImI essential for
      binding to the alpha7/5HT-3 receptor. The first is the triad Asp-Pro-Arg in the
      first loop, where conservative mutations of each residue diminish affinity by 2-3
      orders of magnitude. The second region is the lone Trp in the second loop, where
      an aromatic side chain is required. The overall results suggest that within the
      triad of the first loop, Pro positions the flanking Asp and Arg for optimal
      interaction with one portion of the binding site, while within the second loop,
      Trp stabilizes the complex through its aromatic ring.

PMID- 9556582
TI  - Differential regulation of formyl peptide and platelet-activating factor
      receptors. Role of phospholipase Cbeta3 phosphorylation by protein kinase A.
AB  - Formylated peptides (e.g. n-formyl-Met-Leu-Phe (fMLP)) and platelet-activating
      factor (PAF) mediate chemotactic and cytotoxic responses in leukocytes through
      receptors coupled to G proteins that activate phospholipase C (PLC). In RBL-2H3
      cells, fMLP utilizes a pertussis toxin (ptx)-sensitive G protein to activate PLC,
      whereas PAF utilizes a ptx-insensitive G protein. Here we demonstrate that fMLP,
      but not PAF, enhanced intracellular cAMP levels via a ptx-sensitive mechanism.
      Protein kinase A (PKA) inhibition by H-89 enhanced inositol phosphate formation
      stimulated by fMLP but not PAF. Furthermore, a membrane-permeable cAMP analog 8
      (4-chlorophenylthio)-cAMP (cpt-cAMP) inhibited phosphoinositide hydrolysis and
      secretion stimulated by fMLP but not PAF. Both cpt-cAMP and fMLP stimulated
      PLCbeta3 phosphorylation in intact RBL cells. The purified catalytic subunit of
      PKA phosphorylated PLCbeta3 immunoprecipitated from RBL cell lysate. Pretreatment
      of intact cells with cpt-cAMP and fMLP, but not PAF, resulted in an inhibition of
      subsequent PLCbeta3 phosphorylation by PKA in vitro. These data demonstrate that
      fMLP receptor, which couples to a ptx-sensitive G protein, activates both PLC and
      cAMP production. The resulting PKA activation phosphorylates PLCbeta3 and appears
      to block the ability of Gbetagamma to activate PLC. Thus, both fMLP and PAF
      generate stimulatory signals for PLCbeta3, but only fMLP produces a PKA-dependent
      inhibitory signal. This suggests a novel mechanism for the bidirectional
      regulation of receptors which activate PLC by ptx-sensitive G proteins.

PMID- 9556583
TI  - Membrane-permeant esters of phosphatidylinositol 3,4,5-trisphosphate.
AB  - Phosphoinositide 3-OH kinases and their products, D-3 phosphorylated
      phosphoinositides, are increasingly recognized as crucial elements in many
      signaling cascades. A reliable means to introduce these lipids into intact cells
      would be of great value for showing the physiological roles of this pathway and
      for testing the specificity of pharmacological inhibitors of the kinases. We have
      stereospecifically synthesized di-C8-PIP3/AM and di-C12-PIP3/AM, the
      heptakis(acetoxymethyl) esters of dioctanoyl- and dilauroylphosphatidylinositol
      3,4,5-trisphosphate, in 14 steps from myo-inositol. The ability of these
      uncharged lipophilic derivatives to deliver phosphatidylinositol 3,4,5
      trisphosphate across cell membranes was demonstrated on 3T3-L1 adipocytes and T84
      colon carcinoma monolayers. Insulin stimulation of hexose uptake into adipocytes
      was inhibited by the kinase inhibitor wortmannin and was largely restored by di
      C8-PIP3/AM, which had no effect in the absence of insulin. Thus
      phosphatidylinositol 3,4,5-trisphosphate or a metabolite was necessary but not
      sufficient for stimulation of hexose transport. In T84 epithelial monolayers, di
      C12-PIP3/AM mimicked epidermal growth factor in inhibiting chloride secretion and
      potassium efflux, suggesting that phosphatidylinositol 3,4, 5-trisphosphate was
      sufficient to modulate these fluxes and mediate epidermal growth factor's action.

PMID- 9556584
TI  - Induction of ceramide-mediated apoptosis by the anticancer phospholipid analog,
      hexadecylphosphocholine.
AB  - The prototype of a new class of antiproliferative phospholipid analogs,
      hexadecylphosphocholine (HePC), has been shown to inhibit tumor growth and is
      currently used for the treatment of cutaneous metastases of mammary carcinomas.
      Although several cellular targets of HePC, e.g. protein kinase C and
      CTP:phosphocholine cytidylyltransferase, have been proposed, the mechanisms of
      HePC-induced anticancer activity are still unclear. Considering that the
      antiproliferative effect of HePC correlates with inhibition of
      phosphatidylcholine biosynthesis, which is tightly coupled to sphingomyelin
      biosynthesis, we tested the hypothesis that treatment of cells with the
      anticancer drug leads to increased cellular ceramide and subsequently to
      apoptotic cell death. In the present study, we showed that 25 micromol/liter HePC
      induced apoptosis. In further experiments, we demonstrated that HePC inhibited
      the incorporation of radiolabeled choline into phosphatidylcholine and at a later
      time point into sphingomyelin. This was confirmed by metabolic labeling of the
      lipid backbone using radiolabeled serine, and it was shown that HePC decreased
      the incorporation of serine into sphingomyelin by 35% and simultaneously
      increased the incorporation of serine into ceramide by 70%. Determination of the
      amount of ceramide revealed an increase of 53% in HePC-treated cells compared
      with controls. In accordance with the hypothesis that elevated ceramide levels
      may be the missing link between the metabolic effects of HePC and its
      proapoptotic properties, HePC-induced apoptosis was blocked by fumonisin B1, an
      inhibitor of ceramide synthesis. Furthermore, we found that membrane-permeable
      ceramides additively increased the apoptotic effect of HePC.

PMID- 9556585
TI  - The small heat-shock protein IbpB from Escherichia coli stabilizes stress
      denatured proteins for subsequent refolding by a multichaperone network.
AB  - The role of small heat-shock proteins in Escherichia coli is still enigmatic. We
      show here that the small heat-shock protein IbpB is a molecular chaperone that
      assists the refolding of denatured proteins in the presence of other chaperones.
      IbpB oligomers bind and stabilize heat-denatured malate dehydrogenase (MDH) and
      urea-denatured lactate dehydrogenase and thus prevent the irreversible
      aggregation of these proteins during stress. While IbpB-stabilized proteins alone
      do not refold spontaneously, they are specifically delivered to the
      DnaK/DnaJ/GrpE (KJE) chaperone system where they refold in a strict ATPase
      dependent manner. Although GroEL/GroES (LS) chaperonins do not interact directly
      with IbpB-released proteins, LS accelerate the rate of KJE-mediated refolding of
      IbpB-released MDH, and to a lesser extent lactate dehydrogenase, by rapidly
      processing KJE-released early intermediates. Kinetic and gel-filtration analysis
      showed that denatured MDH preferentially transfers from IbpB to KJE, then from
      KJE to LS, and then forms a active enzyme. IbpB thus stabilizes aggregation-prone
      folding intermediates during stress and, as an integral part of a cooperative
      multichaperone network, is involved in the active refolding of stress-denatured
      proteins.

PMID- 9556586
TI  - Production of nitric oxide by mitochondria.
AB  - The production of NO. by mitochondria was investigated by electron paramagnetic
      resonance using the spin-trapping technique, and by the oxidation of
      oxymyoglobin. Percoll-purified rat liver mitochondria exhibited a negligible
      contamination with other subcellular fractions (1-4%) and high degree of
      functionality (respiratory control ratio = 5-6). Toluene-permeabilized
      mitochondria, mitochondrial homogenates, and a crude preparation of nitric oxide
      synthase (NOS) incubated with the spin trap N-methyl-D-glucamine-dithiocarbamate
      FeII produced a signal ascribed to the NO. spin adduct (g = 2.04; aN = 12.5 G).
      The intensity of the signal increased with time, protein concentration, and L
      Arg, and decreased with the addition of the NOS inhibitor NG-monomethyl-L
      arginine. Intact mitochondria, mitochondrial homogenates, and submitochondrial
      particles produced NO. (followed by the oxidation of oxymyoglobin) at rates of
      1.4, 4.9, and 7.1 nmol NO. x (min.mg protein)-1, respectively, with a Km for L
      Arg of 5-7 microM. Comparison of the rates of NO. production obtained with
      homogenates and submitochondrial particles indicated that most of the enzymatic
      activity was localized in the mitochondrial inner membrane. This study
      demonstrates that mitochondria are a source of NO., the production of which may
      effect energy metabolism, O2 consumption, and O2 free radical formation.

PMID- 9556587
TI  - Purification and characterization of a nitric-oxide synthase from rat liver
      mitochondria.
AB  - The biosynthesis of nitric oxide (NO.) in different cell types occurs
      concomitantly with the conversion of L-arginine to L-citrulline by the enzyme
      nitric-oxide synthase (NOS). NO. has been identified as a major participant in a
      number of basic physiological functions such as neurotransmission, vasodilation,
      and immune response. At the subcellular level, mitochondria have been identified
      as targets for NO.; however, to date, no unambiguous evidence has been presented
      to identify these organelles as sources of NO.. In this study, a NOS was isolated
      to homogeneity from Percoll-purified rat liver mitochondria. Kinetic parameters,
      molecular weight, requirement of cofactors, and cross-reactivity to monoclonal
      antibodies against macrophage NOS suggest similarities to the inducible form.
      However, the constitutive expression of the mitochondrial enzyme and its main
      membrane localization indicate the presence of either a distinctive isoform or a
      macrophage isoform containing posttranslational modifications that lead to
      different subcellular compartments. The detection of NADPH-oxidizing activities
      and a production of superoxide anion catalyzed by mtNOS and recombinant
      cytochrome P450 reductase were consistent with the sequence homology reported for
      these two proteins. Given the role of NO. as cellular transmitter, messenger, or
      regulator, the presence of a functionally active mitochondrial NOS may have
      important implications for the intermediary metabolism.

PMID- 9556588
TI  - Acyl coenzyme A binding protein. Conformational sensitivity to long chain fatty
      acyl-CoA.
AB  - Cellular unbound long chain fatty acyl-CoAs (>14 carbon) are potent regulators of
      gene transcription and intracellular signaling. Although the cytosolic acyl-CoA
      binding protein (ACBP) has high affinity for medium chain fatty acyl-CoAs, direct
      interaction of ACBP with >14-carbon fatty acyl-CoAs has not been established.
      Steady state, photon counting fluorescence spectroscopy directly established that
      rat liver ACBP bound 18-carbon cis- and trans-parinaroyl-CoA, Kd = 7.03 +/- 0.95
      and 4.40 +/- 0.43 nM. Time-resolved fluorometry revealed that ACBP-bound
      parinaroyl-CoAs had high rotational freedom within the single, relatively
      hydrophobic (epsilon <32), binding site. Tyr and Trp fluorescence dynamics
      demonstrated that apo-ACBP was an ellipsoidal protein (axes of 15 and 9 A) whose
      conformation was altered by oleoyl-CoA in the holo-ACBP as shown by a 2-A
      decrease of ACBP hydrodynamic diameter and increased Trp segmental motions. Thus,
      native liver ACBP binds >14-carbon fatty acyl-CoAs with nanomolar affinity at a
      single binding site. Acyl-CoA-induced conformational alterations in ACBP may be
      significant to its putative functions in lipid metabolism and regulation of
      processes sensitive to unbound long chain fatty acyl-CoAs.

PMID- 9556589
TI  - Functional modulation of human recombinant gamma-aminobutyric acid type A
      receptor by docosahexaenoic acid.
AB  - Human gamma-aminobutyric acid type A (GABAA) receptors were expressed in the
      baculovirus/Sf-9 insect cell expression system using recombinant cDNA of
      alpha1beta2gamma2s subunits. The effect of unsaturated fatty acids on GABAA
      receptor complexes was investigated electrophysiologically using conventional
      whole cell recording under voltage clamp. Three distinct effects of
      docosahexaenoic acid (DHA) on the GABA responses were observed. First, DHA, at a
      concentration of 10(-7) M or greater, accelerated the desensitization after the
      peak of the GABA-induced current. Second, DHA (10(-6) M) potentiated the peak
      amplitude of GABA response. This potentiation by DHA was inhibited in the
      presence of Zn2+ (10(-5) M); Cu2+ and Ni2+ mimicked the action of Zn2+. Zn2+ (10(
      5) M) did not block the GABA response on alpha1beta2gamma2s receptor complexes.
      Third, DHA, at a concentration of 3 x 10(-6) M or higher, gradually suppressed
      the peak amplitude of GABA response. A protein kinase A inhibitor, a protein
      kinase C inhibitor, and a Ca2+ chelator did not modify the effects of DHA on GABA
      induced chloride ion current. Six unsaturated fatty acids other than DHA were
      examined. Arachidonic acid mimicked the effect of DHA while e.g. oleic acid had
      no effect. The inhibition of the GABA response in the presence of DHA was also
      observed in cells expressing GABAA receptors of alpha1 and beta2 subunit
      combinations. The data show that the gamma subunit is essential for DHA and
      arachidonic acid to potentiate the GABA-induced Cl- channel activity and to
      affect the desensitization kinetics of the GABAA receptor.

PMID- 9556590
TI  - Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in
      Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae gene SYR2, necessary for growth inhibition by the
      cyclic lipodepsipeptide syringomycin E, is shown to be required for 4
      hydroxylation of long chain bases in sphingolipid biosynthesis. Four lines of
      support for this conclusion are presented: (a) the predicted Syr2p shows sequence
      similarity to diiron-binding membrane enzymes involved in oxygen-dependent
      modifications of hydrocarbon substrates, (b) yeast strains carrying a disrupted
      SYR2 allele produced sphingoid long chain bases lacking the 4-hydroxyl group
      present in wild type strains, (c) 4-hydroxylase activity was increased in
      microsomes prepared from a SYR2 overexpression strain, and (d) the syringomycin E
      resistance phenotype of a syr2 mutant strain was suppressed when grown under
      conditions in which exogenous 4-hydroxysphingoid long chain bases were
      incorporated into sphingolipids. The syr2 strain produced wild type levels of
      sphingolipids, substantial levels of hydroxylated very long chain fatty acids,
      and the full complement of normal yeast sphingolipid head groups. These results
      show that the SYR2 gene is required for the 4-hydroxylation reaction of
      sphingolipid long chain bases, that this hydroxylation is not essential for
      growth, and that the 4-hydroxyl group of sphingolipids is necessary for
      syringomycin E action on yeast.

PMID- 9556591
TI  - Induction of chromosomal gene mutations in Escherichia coli by direct
      incorporation of oxidatively damaged nucleotides. New evaluation method for
      mutagenesis by damaged DNA precursors in vivo.
AB  - We have developed a new strategy for the evaluation of the mutagenicity of a
      damaged DNA precursor (deoxyribonucleoside 5'-triphosphate) in Escherichia coli.
      8-Hydroxydeoxyguanosine triphosphate (8-OH-dGTP) and 2-hydroxydeoxyadenosine
      triphosphate (2-OH-dATP) were chosen for this study because they appear to be
      formed abundantly by reactive oxygen species in cells. We introduced the
      oxidatively damaged nucleotides into competent E. coli and selected mutants of
      the chromosomal lacI gene. Both damaged nucleotides induced lacI gene mutations
      in a dose-dependent manner, whereas unmodified dATP and dGTP did not appear to
      elicit the mutations. The addition of 50 nmol of 8-OH-dGTP and 2-OH-dATP into an
      E. coli suspension induced 12- and 9-fold more substitution mutations than the
      spontaneous event, respectively. The 8-OH-dGTP induced A.T --> C.G transversions,
      and the 2-OH-dATP elicited G.C --> T.A transversions. These results indicate that
      the two oxidatively damaged nucleotides are mutagenic in vivo and suggest that 8
      OH-dGTP and 2-OH-dATP were incorporated opposite A and G residues, respectively,
      in the E. coli DNA. This new method enables the evaluation and comparison of the
      mutagenic potentials of damaged DNA precursors in vivo.

PMID- 9556592
TI  - Regions of association between the alpha and the beta subunit of the gastric H,K
      ATPase.
AB  - A binding and a yeast two-hybrid analysis were carried out on the gastric H,K
      ATPase to determine interactive regions of the extracytoplasmic domains of the
      alpha and beta subunits of this P type ATPase. Wheat germ agglutinin
      fractionation of fluorescein 5-maleimide-labeled tryptic fragments of detergent
      solubilized H, K-ATPase showed that a fragment Leu855 to Arg922 of the alpha
      subunit was bound to the beta subunit. The yeast two-hybrid system showed that
      the region containing only a part of the seventh transmembrane segment, the loop,
      and part of the eighth transmembrane segment was capable of giving positive
      interaction signals with the ectodomain of the beta subunit. The sequence in the
      extracytoplasmic loop close to the eighth transmembrane segment, namely Arg898 to
      Thr928, was identified as being the site of interaction using this method. We
      deduced that the sequence Arg898 to Arg922 in the alpha subunit has strong
      interaction with the extracytoplasmic domain of the beta subunit. Again, using
      yeast two-hybrid analysis, two different sequences in the beta subunit Gln64 to
      Asn130 and Ala156 to Arg188 were identified as association domains in the
      extracytoplasmic sequence of the beta subunit. These data enable identification
      of major associative regions of the alpha-beta subunits of the H,K-ATPase.

PMID- 9556593
TI  - Biophysical, biochemical, and physiological characterization of Chlamydomonas
      reinhardtii mutants with amino acid substitutions at the Ala251 residue in the D1
      protein that result in varying levels of photosynthetic competence.
AB  - The QB binding site of the D1 reaction center protein, located within a stromal
      loop between transmembrane helices IV and V formed by residues Ile219 to Leu272,
      is essential for photosynthetic electron transport through photosystem II (PSII).
      We have examined the function of the highly conserved Ala251 D1 residue in this
      domain in chloroplast transformants of Chlamydomonas reinhardtii and found that
      Arg, Asp, Gln, Glu, and His substitutions are nonphotosynthetic, whereas Cys,
      Ser, Pro, Gly, Ile, Val, and Leu substitutions show various alterations in D1
      turnover, photosynthesis, and photoautotrophic growth. The latter mutations
      reduce the rate of QA to QB electron transfer, but this is not necessarily rate
      limiting for photoautotrophic growth. The Cys mutant divides and evolves O2 at
      wild type rates, although it has slightly higher rates of D1 synthesis and
      turnover and reduced electron transfer between QA and QB. O2 evolution, D1
      synthesis, and accumulation in the Ser, Pro, and Gly mutants in high light is
      reduced, but photoautotrophic growth rate is not affected. In contrast, the Ile,
      Val, and Leu mutants are impaired in photoautotrophic growth and photosynthesis
      in both low and high light and have elevated rates of D1 synthesis and
      degradation, but D1 accumulation is normal. While rates of synthesis/degradation
      of the D1 protein are not necessarily correlated with alterations in specific
      parameters of PSII function in these mutants, bulkiness of the substituted amino
      acids is highly correlated with the dissociation constant for QB in the seven
      mutants examined. These observations imply that the Ala251 residue plays a key
      role in D1 protein.

PMID- 9556594
TI  - Regulatory interactions between the human HOXB1, HOXB2, and HOXB3 proteins and
      the upstream sequence of the Otx2 gene in embryonal carcinoma cells.
AB  - Vertebrate Hox and Otx genes encode homeodomain-containing transcription factors
      thought to transduce positional information along the body axis in the segmental
      portion of the trunk and in the rostral brain, respectively. Moreover, Hox and
      Otx2 genes show a complementary spatial regulation during embryogenesis. In this
      report, we show that a 1821-base pair (bp) upstream DNA fragment of the Otx2 gene
      is positively regulated by co-transfection with expression vectors for the human
      HOXB1, HOXB2, and HOXB3 proteins in an embryonal carcinoma cell line (NT2/D1) and
      that a shorter fragment of only 534 bp is able to drive this regulation. We also
      identified the HOXB1, HOXB2, and HOXB3 DNA-binding region on the 534-bp Otx2
      genomic fragment using nuclear extracts from Hox-transfected COS cells and 12.5
      days postcoitum mouse embryos or HOXB3 homeodomain-containing bacterial extracts.
      HOXB1, HOXB3, and nuclear extracts from 12.5 days postcoitum mouse embryos bind
      to a sequence containing two palindromic TAATTA sites, which bear four copies of
      the ATTA core sequence, a common feature of most HOM-C/HOX binding sites. HOXB2
      protected an adjacent site containing a direct repeat of an ACTT sequence, quite
      divergent from the ATTA consensus. The region bound by the three homeoproteins is
      strikingly conserved through evolution and necessary (at least for HOXB1 and
      HOXB3) to mediate the up-regulation of the Otx2 transcription. Taken together,
      our data support the hypothesis that anteriorly expressed Hox genes might play a
      role in the refinement of the Otx2 early expression boundaries in vivo.

PMID- 9556595
TI  - Post-translational processing and turnover kinetics of presynaptically targeted
      amyloid precursor superfamily proteins in the central nervous system.
AB  - The amyloid precursor superfamily is composed of three highly conserved
      transmembrane glycoproteins, the amyloid precursor protein (APP) and amyloid
      precursor-like proteins 1 and 2 (APLP1, APLP2), whose functions are unknown.
      Proteolytic cleavage of APP yields the betaA4 peptide, the major component of
      cerebral amyloid in Alzheimer's disease. Here we show that five post
      translationally modified, full-length species of APP and APLP2 (but not APLP1)
      arrive at the mature presynaptic terminal in the fastest wave of axonal transport
      and are subsequently rapidly cleared (mean half-life of 3.5 h). Rapid turnover of
      presynaptic APP and APLP2 occurs independently of visual activity. Turnover of
      the most rapidly arriving APP species was accompanied by a delayed accumulation
      of a 120-kDa, APP fragment lacking the C terminus, consistent with presynaptic
      APP turnover via constitutive proteolysis. Turnover of APLP2 was not accompanied
      by detectable APLP2 fragment peptides, suggesting either that APLP2 either is
      more rapidly degraded than is APP or is retrogradely transported shortly after
      reaching the terminus. A single 150-kDa APLP2 species containing the Kunitz
      protease inhibitor domain is the major amyloid precursor superfamily protein
      transported to the presynapse. Presynaptic APP and APLP2 are sialylated and N-
      and O-glycosylated, and some also carry chondroitin sulfate glycosaminoglycan
      and/or dermatan sulfate glycosaminoglycan. The rapid kinetics for turnover of APP
      and APLP2 predict a sensitive balance of synthesis, transport, and elimination
      rates that may be critical to normal neuronal functions and metabolic fates of
      these proteins.

PMID- 9556596
TI  - Regulatory roles of the P domain of the subtilisin-like prohormone convertases.
AB  - A unique feature of the eukaryotic subtilisin-like proprotein convertases (SPCs)
      is the presence of an additional highly conserved sequence of approximately 150
      residues (P domain) located immediately downstream of the catalytic domain. To
      study the function of this region, which is required for the production of
      enzymatically active convertases, we have expressed and characterized various P
      domain-related mutants and chimeras in HEK293 cells and alpha-TC1-6 cells. In a
      series of C-terminal truncations of PC3 (also known as PC1 or SPC3), PC3-Thr594
      was identified as the shortest active form, thereby defining the functional C
      terminal boundary of the P domain. Substitutions at Thr594 and nearby sites
      indicated that residues 592-594 are crucial for activity. Chimeric SPC proteins
      with interchanged P domains demonstrated dramatic changes in several properties.
      Compared with truncated wild-type PC3 (PC3-Asp616), both PC3/PC2Pd and PC3/FurPd
      had elevated activity on several synthetic substrates as well as reduced calcium
      ion dependence, whereas Fur/PC2Pd was only slightly decreased in activity as
      compared with truncated furin (Fur-Glu583). Of the three active SPC chimeras
      tested, all had more alkaline pH optima. When PC3/PC2Pd was expressed in alpha
      TC1-6 cells, it accelerated the processing of proglucagon into glicentin and
      major proglucagon fragment and cleaved major proglucagon fragment to release GLP
      1 and tGLP-1, similar to wild-type PC3. Thus, P domain exchanges generated fully
      active chimeric proteases in several instances but not in all (e.g. PC2/PC3Pd was
      inactive). The observed property changes indicate a role for the P domain in
      regulating the stability, calcium dependence, and pH dependence of the
      convertases.

PMID- 9556597
TI  - The alpha-helical domain near the amino terminus is essential for dimerization of
      vascular endothelial growth factor.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen
      and a key mediator of aberrant endothelial cell proliferation and vascular
      permeability in a variety of human pathological situations such as tumor
      angiogenesis, diabetic retinopathy, or psoriasis. By amino-terminal deletion
      analysis and by site-directed mutagenesis we have identified a new domain within
      the amino-terminal alpha-helix that is essential for dimerization of VEGF.
      VEGF121 variants containing amino acids 8 to 121 or 14 to 121, respectively,
      either expressed in Escherichia coli and refolded in vitro, or expressed in
      Chinese hamster ovary cells, were in a dimeric conformation and showed full
      binding activity to VEGF receptors and stimulation of endothelial cell
      proliferation as compared with wild-type VEGF. In contrast, a VEGF121 variant
      covering amino acids 18 to 121, as well as a variant in which the hydrophobic
      amino acids Val14, Val15, Phe17, and Met18 within the amphipathic alpha-helix
      near the amino terminus were replaced by serine, failed to form biological active
      VEGF dimers. From these data we conclude that a domain between amino acids His12
      and Asp19 within the amino-terminal alpha-helix is essential for formation of
      VEGF dimers, and we propose hydrophobic interactions between VEGF monomers to
      stabilize or favor dimerization.

PMID- 9556598
TI  - Functional analysis of the amino-terminal 8-kDa domain of DNA polymerase beta as
      revealed by site-directed mutagenesis. DNA binding and 5'-deoxyribose phosphate
      lyase activities.
AB  - The amino-terminal 8-kDa domain of DNA polymerase beta functions in binding
      single-stranded DNA (ssDNA), recognition of a 5'-phosphate in gapped DNA
      structures, and as a 5'-deoxyribose phosphate (dRP) lyase. NMR and x-ray crystal
      structures of this domain have suggested several residues that may interact with
      ssDNA or play a role in the dRP lyase reaction. Nine of these residues were
      altered by site-directed mutagenesis. Each mutant was expressed in Escherichia
      coli, and the recombinant protein was purified to near homogeneity. CD spectra of
      these mutant proteins indicated that the alteration did not adversely affect the
      global protein structure. Single-stranded DNA binding was probed by photochemical
      cross-linking to oligo(dT)16. Several mutants (F25W, K35A, K60A, and K68A) were
      impaired in ssDNA binding activity, whereas other mutants (H34G, E71Q, K72A,
      E75A, and K84A) retained near wild-type binding activity. The 5'-phosphate
      recognition activity of these mutants was examined by UV cross-linking to a 5
      nucleotide gap DNA where the 5' terminus in the gap was either phosphorylated or
      unphosphorylated. The results indicate that Lys35 is involved in 5'-phosphate
      recognition of DNA polymerase beta. Finally, the dRP lyase activity of these
      mutants was evaluated using a preincised apurinic/apyrimidinic DNA. Alanine
      mutants of Lys35 and Lys60 are significantly reduced in dRP lyase activity,
      consistent with the lower ssDNA binding activity. More importantly, alanine
      substitution for Lys72 resulted in a greater than 90% loss of dRP lyase activity,
      without affecting DNA binding. Alanine mutants of Lys68 and Lys84 had wild-type
      dRP lyase activity. The triple alanine mutant, K35A/K68A/K72A, was devoid of dRP
      lyase activity, suggesting that the effects of the alanine substitution at Lys72
      and Lys35 were additive. The results suggest that Lys72 is directly involved in
      formation of a covalent imino intermediate and are consistent with Lys72 as the
      predominant Schiff base nucleophile in the dRP lyase beta-elimination catalytic
      reaction.

PMID- 9556599
TI  - Characterization of a split respiratory pathway in the wheat "take-all" fungus,
      Gaeumannomyces graminis var. tritici.
AB  - This article describes the first detailed analysis of mitochondrial electron
      transfer and oxidative phosphorylation in the pathogenic filamentous fungus,
      Gaeumannomyces graminis var. tritici. While oxygen consumption was cyanide
      insensitive, inhibition occurred following treatment with complex III inhibitors
      and the alternative oxidase inhibitor, salicylhydroxamic acid (SHAM). Similarly,
      maintenance of a Deltapsi across the mitochondrial inner membrane was unaffected
      by cyanide but sensitive to antimycin A and SHAM when succinate was added as the
      respiratory substrate. As a result, ATP synthesis through complex V was
      demonstrated to be sensitive to these two inhibitors but not to cyanide. Analysis
      of the cytochrome content of mitochondria indicated the presence of those
      cytochromes normally associated with electron transport in eukaryotic
      mitochondria together with a third, b-type heme, exhibiting a dithionite-reduced
      absorbance maxima at 560 nm and not associated with complex III. Antibodies
      raised to plant alternative oxidase detected the presence of both the monomeric
      and dimeric forms of this oxidase. Overall this study demonstrates that a novel
      respiratory chain utilizing the terminal oxidases, cytochrome c oxidase and
      alternative oxidase, are present and constitutively active in electron transfer
      in G. graminis tritici. These results are discussed in relation to current
      understanding of fungal electron transfer and to the possible contribution of
      alternative redox centers in ATP synthesis.

PMID- 9556600
TI  - Substrate binding and catalytic mechanism of a barley beta-D-Glucosidase/(1,4)
      beta-D-glucan exohydrolase.
AB  - A beta-glucosidase, designated isoenzyme betaII, from germinated barley (Hordeum
      vulgare L.) hydrolyzes aryl-beta-glucosides and shares a high level of amino acid
      sequence similarity with beta-glucosidases of diverse origin. It releases glucose
      from the non-reducing termini of cellodextrins with catalytic efficiency factors,
      kcat/Km, that increase approximately 9-fold as the degree of polymerization of
      these substrates increases from 2 to 6. Thus, the enzyme has a specificity and
      action pattern characteristic of both beta-glucosidases (EC 3.2.1.21) and the
      polysaccharide exohydrolase, (1,4)-beta-glucan glucohydrolase (EC 3.2.1.74). At
      high concentrations (100 mM) of 4-nitrophenyl beta-glucoside, beta-glucosidase
      isoenzyme betaII catalyzes glycosyl transfer reactions, which generate 4
      nitrophenyl-beta-laminaribioside, -cellobioside, and -gentiobioside. Subsite
      mapping with cellooligosaccharides indicates that the barley beta-glucosidase
      isoenzyme betaII has six substrate-binding subsites, each of which binds an
      individual beta-glucosyl residue. Amino acid residues Glu181 and Glu391 are
      identified as the probable catalytic acid and catalytic nucleophile,
      respectively. The enzyme is a family 1 glycoside hydrolase that is likely to
      adopt a (beta/alpha)8 barrel fold and in which the catalytic amino acid residues
      appear to be located at the bottom of a funnel-shaped pocket in the enzyme.

PMID- 9556601
TI  - Tyrosine phosphorylation of p130Cas is involved in actin organization in
      osteoclasts.
AB  - Integrin-mediated interaction with the extracellular matrix plays a critical role
      in the function of osteoclasts, the bone-resorbing cells. This study examines the
      role of p130Cas (Crk-associated substrate (Cas)) in actin organization in
      osteoclasts. Multinucleated osteoclast-like cells (OCLs) were obtained in a co
      culture of murine bone marrow cells and primary osteoblasts. After plating on
      culture dishes, OCLs formed a ringlike structure consisting of F-actin dots at
      cell periphery (actin ring). The percentage of OCLs with actin rings and its
      diameter increased with time and cell spreading. Tyrosine phosphorylation of a
      protein (p130) increased with actin ring formation. Treatment with cytochalasin D
      disrupted actin rings and reduced tyrosine phosphorylation of p130. Using
      specific antibodies, p130 was identified as Cas. By immunocytochemistry, Cas was
      localized to the peripheral regions of OCLs and its distribution overlapped that
      of F-actin. In OCLs derived from Src(-/-) mice, in which osteoclast activity is
      severely compromised, tyrosine phosphorylation of Cas was markedly reduced.
      Moreover, Cas was diffusely distributed in the cytoplasm and actin ring formation
      is not observed. These findings suggest that Src-dependent tyrosine
      phosphorylation of Cas is involved in the adhesion-induced actin organization
      associated with osteoclast activation.

PMID- 9556602
TI  - Disulfide bond structure of human epidermal growth factor receptor.
AB  - The extracellular domain of the human epidermal growth factor receptor (sEGFR)
      consists of 621 amino acid residues, including 50 cysteines. The connections of
      the 25 disulfide bonds in the recombinant sEGFR protein, obtained from Chinese
      hamster ovary cells, have been determined using N-terminal sequencing and matrix
      assisted laser desorption/ionization mass spectroscopy. We identified a basic
      repeat of eight cysteines with a 1-3, 2-4, 5-6, and 7-8 disulfide pairing pattern
      in the two cysteine-rich regions of sEGFR. By comparison to other cysteine-rich
      motifs, it was concluded that the cysteine-rich repeat of sEGFR belongs to the
      laminin-type EGR-like (LE) structural motif. Three-dimensional structure models
      of the two cysteine-rich regions have been built, based on the three-dimensional
      structures of the LE domains from the laminin gamma1 chain and secondary
      structure predictions for the EGF receptor.

PMID- 9556603
TI  - Differentiation of glycine antagonist sites of N-methyl-D-aspartate receptor
      subtypes. Preferential interaction of CGP 61594 with NR1/2B receptors.
AB  - The binding site for the co-agonist glycine on N-methyl-D-aspartate (NMDA)
      receptors has been mapped to the NR1 subunit whereas binding of the principal
      agonist glutamate is mediated by the NR2 subunits. Using the novel glycine site
      antagonist and photoaffinity label CGP 61594, distinct contributions of the NR2
      subunit variants to the glycine antagonist binding domains of NMDA receptor
      subtypes are demonstrated. High affinity sites for CGP 61594 were exclusively
      displayed by NR1/2B receptors, as shown by their co-distribution with the NR2B
      subunit, by subunit-selective immunoprecipitation and by functional analysis of
      NR1/2B receptors expressed in Xenopus oocytes (inhibitory potency, IC50 = 45 +/-
      11 nM). Other NMDA receptor subtypes are clearly distinguished by reduced
      inhibitory potencies for CGP 61594, being low for NR1/2A and NR1/2D receptors
      (IC50 = 430 +/- 105 nM and 340 +/- 61 nM, respectively) and intermediate for
      NR1/2C receptors (IC50 = 164 +/- 27 nM). Glycine antagonist sites with low and
      intermediate affinity for [3H]CGP 61594 were detected also in situ by radioligand
      binding in brain areas predominantly expressing the NR2A and NR2C subunits,
      respectively. Thus, [3H]CGP 61594 is the first antagonist radioligand that
      reliably distinguishes the glycine site of NMDA receptor subtypes. [3H]CGP 61594
      is a promising tool to identify the NR2 subunit domains that contribute to
      differential glycine antagonist sites of NMDA receptor subtypes.

PMID- 9556604
TI  - Inability of the acidic fibroblast growth factor mutant K132E to stimulate DNA
      synthesis after translocation into cells.
AB  - Acidic fibroblast growth factor (aFGF) is a potent mitogen. It acts through
      activation of specific cell surface receptors leading to intracellular tyrosine
      phosphorylation cascades, but several reports also indicate that aFGF enters
      cells and that it has an intracellular function as well. The aFGF(K132E) mutant
      binds to and activates fibroblast growth factor receptors equally strongly as the
      wild-type, but it is a poor mitogen. We demonstrate that aFGF(K132E) enters NIH
      3T3 cells and is transported to the nuclear fraction like wild-type aFGF. A
      fusion protein of aFGF(K132E) and diphtheria toxin A-fragment (aFGF(K132E)-DT-A)
      and a similar fusion protein containing wild-type aFGF (aFGF-DT-A) were
      reconstituted with diphtheria toxin B-fragment. Both fusion proteins were
      translocated to the cytosol by the diphtheria toxin pathway and subsequently
      recovered from the nuclear fraction. Whereas translocation of aFGF-DT-A
      stimulated DNA synthesis in U2OSDR1 cells lacking functional fibroblast growth
      factor receptors, aFGF(K132E)-DT-A did not. The mutation disrupts a protein
      kinase C phosphorylation site in the growth factor making it unable to be
      phosphorylated. The data indicate that a defect in the intracellular action of
      aFGF(K132E) is the reason for its strongly reduced mitogenicity, possibly due to
      inability to be phosphorylated.

PMID- 9556605
TI  - Homodimerization restores biological activity to an inactive erythropoietin
      mutant.
AB  - Erythropoietin (Epo) is believed to transduce a signal by bringing two Epo
      receptors into close proximity, enabling cross-phosphorylation. We compared
      monomeric Epos with homodimers in which two Epo monomers are linked by
      polyglycine. Monomeric Epo mutant R103A is unable to support Epo-dependent cell
      growth or trigger Janus kinase 2 and STAT5 activation, even at concentrations
      greater than 7,000 times that sufficient for wild-type Epo activity. In contrast,
      R103A homodimer induces proliferation and transduces signal at concentrations
      similar to that of wild-type Epo monomer and homodimer. These experiments show
      that two discrete domains on Epo are required for receptor binding and
      activation. Our results also suggest that the EpoR can be dimerized by different
      forms and sizes of molecules, as long as two recognition motifs are provided in
      the same molecule. Design of other dimeric molecules may enhance our
      understanding of cytokine specificity and signal transduction.

PMID- 9556606
TI  - Induction of apoptosis and inhibition of cell proliferation by survivin gene
      targeting.
AB  - Survivin is a new IAP apoptosis inhibitor expressed during development and in
      human cancer in vivo. The coding strand of the survivin gene was extensively
      complementary to that of effector cell protease receptor-1 (EPR-1), prompting the
      present investigation on the origin and functional relationship of these two
      transcripts. Southern blots of genomic DNA were consistent with the presence of
      multiple, evolutionarily conserved, EPR-1/Survivin-related genes. By pulsed field
      gel electrophoresis and single- and two-color fluorescence in situ hybridization,
      these were contained within a contiguous physical interval of 75-130 kilobases
      (kb) on chromosome 17q25. In Northern blots, a single strand-specific probe
      identified a 1.3-kb EPR-1 mRNA broadly distributed in normal adult and fetal
      tissues, structurally distinct from the 1.9-kb Survivin transcript expressed in
      transformed cell lines. Transient co-transfection of an EPR-1 cDNA potentially
      acting as a Survivin antisense with a lacZ reporter plasmid resulted in loss of
      viability of HeLa cells. In contrast, co-transfection of an antisense cDNA of
      intercellular adhesion molecule-1 or a sense-oriented Survivin cDNA was without
      effect. In stably transfected HeLa cells, ZnSO4 induction of an EPR-1 mRNA under
      the control of a metallothionein promoter suppressed the expression of endogenous
      survivin. This resulted in (i) increased apoptosis as detected by analysis of DNA
      content and in situ internucleosomal DNA fragmentation and (ii) inhibition of
      cell proliferation as compared with induced vector control transfectants. These
      findings suggest the existence of a potential EPR-1/survivin gene cluster and
      identify survivin as a new target for disrupting cell viability pathways in
      cancer.

PMID- 9556607
TI  - Involvement of heat shock protein 90 in the degradation of mutant insulin
      receptors by the proteasome.
AB  - We previously reported three families with type A insulin-resistant syndrome who
      had mutations, either Asp1179 or Leu1193, in the kinase domain of the insulin
      receptor. The extreme insulin resistance of these patients was found to be caused
      by the decreased number of insulin receptors on the cell surface, due to the
      intracellular rapid degradation (Imamura, T., Takata, Y., Sasaoka, T., Takada,
      Y., Morioka, H., Haruta, T., Sawa, T., Iwanishi, M., Yang, G. H., Suzuki, Y.,
      Hamada, J., and Kobayashi, M. (1994) J. Biol. Chem. 269, 31019-31027). In the
      present study, we first examined whether these mutations caused rapid degradation
      of unprocessed proreceptors, using the exon 13 deleted mutant insulin receptors
      (DeltaEx13-IR), which were accumulated in the endoplasmic reticulum as
      unprocessed proreceptors. The addition of Asp1179 or Leu1193 mutation to
      DeltaEx13-IR caused accelerated degradation of the unprocessed DeltaEx13-IR in
      the transfected COS-7 cells. Next, we tested whether these mutant receptors were
      degraded by the proteasome. Treatment with proteasome inhibitors Z-Leu-Leu-Nva-H
      (MG-115) or Z-Leu-Leu-Leu-H (MG-132) prevented the accelerated degradation of
      these mutant receptors, resulting in increased amounts of the mutant receptors in
      the COS-7 cells. Essentially the same results were obtained in the patient's
      transformed lymphocytes. Finally, we found that these mutant receptors bound to
      heat shock protein 90 (Hsp90). To determine whether Hsp90 played an important
      role in the accelerated receptor degradation, we examined the effect of anti
      Hsp90 antibody on the mutant receptor degradation. The microinjection of anti
      Hsp90 antibody into cells prevented the accelerated degradation of both Asp1179
      and Leu1193 mutant insulin receptors. Taken together, these results suggest that
      Hsp90 is involved in dislocation of the mutant insulin receptors out of the
      endoplasmic reticulum into the cytosol, where the mutant receptors are degraded
      by the proteasome.

PMID- 9556608
TI  - Characterization of recombinant and brain neuropsin, a plasticity-related serine
      protease.
AB  - Activity-dependent changes in neuropsin gene expression in the hippocampus
      implies an involvement of neuropsin in neural plasticity. Since the deduced amino
      acid sequence of the gene contained the complete triplet (His-Asp-Ser) of the
      serine protease domain, the protein was postulated to have proteolytic activity.
      Recombinant full-length neuropsin produced in the baculovirus/insect cell system
      was enzymatically inactive but was readily converted to active enzyme by
      endoprotease processing. The activational processing of prototype neuropsin
      involved the specific cleavage of the Lys32-Ile33 bond near its N terminus.
      Native neuropsin that was purified with a purity of 1,100-fold from mouse brain
      had enzymatic characteristics identical to those of active-type recombinant
      neuropsin. Both brain and recombinant neuropsin had amidolytic activities
      cleaving Arg-X and Lys-X bonds in the synthetic chromogenic substrates, and the
      highest specific activity was found against Boc-Val-Pro-Arg-4-methylcoumaryl-7
      amide. The active-type recombinant neuropsin effectively cleaved fibronectin, an
      extracellular matrix protein. Taken together, these results indicate that this
      protease, which is enzymatically novel, has significant limbic effects by
      changing the extracellular matrix environment.

PMID- 9556609
TI  - Requirements for binding and signaling of the kinase domain receptor for vascular
      endothelial growth factor.
AB  - Vascular endothelial growth factor (VEGF) is a dimeric hormone that controls much
      of vascular development through binding and activation of its kinase domain
      receptor (KDR). We produced analogs of VEGF that show it has two receptor-binding
      sites which are located near the poles of the dimer and straddle the interface
      between subunits. Deletion experiments in KDR indicate that of the seven IgG-like
      domains in the extracellular domain, only domains 2-3 are needed for tight
      binding of VEGF. Monomeric forms of the extracellular domain of KDR bind
      approximately 100 times weaker than dimeric forms showing a strong avidity
      component for binding of VEGF to predimerized forms of the receptor. Based upon
      these structure-function studies and a mechanism in which receptor dimerization
      is critical for signaling, we constructed a receptor antagonist in the form of a
      heterodimer of VEGF that contained one functional and one non-functional site.
      These studies establish a functional foundation for the design of VEGF analogs,
      mimics, and antagonists.

PMID- 9556610
TI  - Galectin-1 is a major receptor for ganglioside GM1, a product of the growth
      controlling activity of a cell surface ganglioside sialidase, on human
      neuroblastoma cells in culture.
AB  - Cell density-dependent inhibition of growth and neural differentiation in the
      human neuroblastoma cell line SK-N-MC are associated with a ganglioside sialidase
      mediated increase of GM1 and lactosylceramide at the cell surface. Because these
      glycolipids expose galactose residues, we have initiated the study of the
      potential role of galectins in such cellular events. Using specific antibodies,
      galectin-1 but not galectin-3 was found to be present at the cell surface.
      Assessment of carbohydrate-dependent binding revealed a saturable amount of
      ligand sites approaching 2.6 x 10(6) galectin-1 molecules bound/cell. Presence
      during cell culture of the sialidase inhibitor 2-deoxy-2,3-dehydro-N
      acetylneuraminic acid or of the GM1-binding cholera toxin B subunit effected a
      decrease of the presentation of galectin-1 ligands by 30-50%. The assumption that
      GM1 is a major ligand for galectin-1 was reinforced by the correlation between
      the number of carbohydrate-dependent 125I-iodinated GM1-neoganglioprotein binding
      sites and the amount of immunoreactive surface galectin-1, the marked sensitivity
      of probe binding to the presence of anti-galectin-1 antibody, and the inhibition
      of cell adhesion to surface-immobilized GM1 by the antibody. The results open the
      possibility that the carbohydrate-dependent interaction between ganglioside GM1
      and galectin-1 may relay sialidase-dependent alterations in this cell system.

PMID- 9556611
TI  - Identification and purification of the Holo-ELL complex. Evidence for the
      presence of ELL-associated proteins that suppress the transcriptional inhibitory
      activity of ELL.
AB  - The human ELL gene on chromosome 19 undergoes frequent translocation with the
      trithorax-like MLL gene on chromosome 11 in acute myeloid leukemia. Recently, it
      was demonstrated that the product of the human ELL gene encodes an RNA polymerase
      II elongation factor (Shilatifard, A., Lane, W. S., Jackson, K. W., Conaway, R.
      C., and Conaway, J. W. (1996) Science 271, 1873-1876). In addition to its
      elongation regulatory activity, ELL contains a novel type of RNA polymerase II
      interaction domain that is capable of negatively regulating polymerase activity
      in promoter-specific transcription in vitro (Shilatifard, A., Haque, D., Conaway,
      R. C., and Conaway, J. W. (1997) J. Biol. Chem. 272, 22355-22363). Here, we
      report the identification and purification of a large ELL-containing complex that
      contains three proteins in addition to ELL and that we have named the Holo-ELL
      complex. The Holo-ELL complex can increase the catalytic rate of transcription
      elongation by RNA polymerase II. However, unlike the ELL polypeptide alone, the
      Holo-ELL complex is not capable of negatively regulating polymerase activity in
      promoter-specific transcription in vitro. The inability of the Holo-ELL complex
      to negatively regulate polymerase activity in promoter-specific transcription
      suggests that one or more of the ELL-associated proteins regulate this activity,
      possibly through an interaction with the N-terminal domain of the ELL protein,
      which was shown to be required for the transcriptional inhibitory activity of
      ELL. Characterization of these ELL interacting proteins should help define the
      regulation of the biochemical activities of ELL and how loss of this regulation
      leads to the development of acute myeloid leukemia.

PMID- 9556612
TI  - Immunolocalization of acyl-coenzyme A:cholesterol O-acyltransferase in
      macrophages.
AB  - Macrophages in atherosclerotic lesions accumulate large amounts of cholesteryl
      fatty acyl esters ("foam cell" formation) through the intracellular
      esterification of cholesterol by acyl-coenzyme A:cholesterol O-acyltransferase
      (ACAT). In this study, we sought to determine the subcellular localization of
      ACAT in macrophages. Using mouse peritoneal macrophages and immunofluorescence
      microscopy, we found that a major portion of ACAT was in a dense reticular
      cytoplasmic network and in the nuclear membrane that colocalized with the luminal
      endoplasmic reticulum marker protein-disulfide isomerase (PDI) and that was in a
      similar distribution as the membrane-bound endoplasmic reticulum marker
      ribophorin. Remarkably, another portion of the macrophage ACAT pattern did not
      overlap with PDI or ribophorin, but was found in as yet unidentified cytoplasmic
      structures that were juxtaposed to the nucleus. Compartments containing labeled
      beta-very low density lipoprotein, an atherogenic lipoprotein, did not overlap
      with the ACAT label, but rather were embedded in the dense reticular network of
      ACAT. Furthermore, cell-surface biotinylation experiments revealed that freshly
      harvested, non-attached macrophages, but not those attached to tissue culture
      dishes, contained approximately 10-15% of ACAT on the cell surface. In summary,
      ACAT was found in several sites in macrophages: a cytoplasmic reticular/nuclear
      membrane site that overlaps with PDI and ribophorin and has the characteristics
      of the endoplasmic reticulum, a perinuclear cytoplasmic site that does not
      overlap with PDI or ribophorin and may be another cytoplasmic structure or
      possibly a unique subcompartment of the endoplasmic reticulum, and a cell-surface
      site in non-attached macrophages. Understanding possible physiological
      differences of ACAT in these locations may reveal an important component of ACAT
      regulation and macrophage foam cell formation.

PMID- 9556613
TI  - Identification of a major carbohydrate capping group of the L-selectin ligand on
      high endothelial venules in human lymph nodes as 6-sulfo sialyl Lewis X.
AB  - We investigated the molecular species of sulfated sialyl Lewis X determinants,
      the putative L-selectin ligand, expressed on high endothelial venules (HEV) in
      human lymph nodes. Comparison of the reactivity pattern of HEV with the
      reactivity of the pure 6-sulfo, 6'-sulfo, or 6,6'-bissulfo sialyl Lewis X
      determinant with hitherto known anti-sialyl Lewis X antibodies strongly suggested
      6-sulfo sialyl Lewis X to be the best candidate for the major sulfated sialyl
      Lewis X determinant on HEV, followed by 6,6'-bissulfo sialyl Lewis X, whereas 6'
      sulfo sialyl Lewis X was unlikely. We newly generated monoclonal antibodies
      (mAbs) G152 and G72 directed against 6-sulfo sialyl Lewis X, which intensely
      labeled HEV in immunohistochemical examination and inhibited binding of
      recombinant L-selectin-IgG to HEV, suggesting that the determinant serves as a
      ligand for L-selectin. To test the concomitant expression of 6, 6'-bissulfo
      sialyl Lewis X, specific mAbs (G2706, G27011, G27037, and G27039) were generated,
      but all antibodies failed to react to HEV. Next, we established mAbs (AG97 and
      AG273) directed against 6-sulfo Lewis X, the asialo form of 6-sulfo sialyl Lewis
      X. The antibodies were not reactive to untreated HEV, but strongly reacted to
      sialidase-treated HEV. This indicated the predominance of the sialylated form of
      6-sulfo sialyl Lewis X and minimal expression of its asialo form, corroborating
      that it was synthesized by fucosyltransferase VII, the isoenzyme that
      preferentially produces the sialylated form of the determinant.

PMID- 9556614
TI  - A divergent member of the transforming growth factor beta receptor family from
      Schistosoma mansoni is expressed on the parasite surface membrane.
AB  - To optimize reproductive success under the limitations determined by conditions
      within an individual host, parasitic helminths have evolved mechanisms that allow
      them to detect and respond to host factors such as species, age, sex,
      reproductive condition, and immune status. Using the model helminth Schistosoma
      mansoni, we have explored the possibility that parasitic helminths express signal
      transducing receptor molecules on their surfaces. Here, we present the
      identification of a schistosome member of the transforming growth factor beta
      receptor family of cell-surface receptors, the first member of this family to be
      identified in a platyhelminth. The putative protein kinase domain of the
      schistosome receptor displays up to 58% amino acid identity to kinase domains of
      other type I receptor serine-threonine kinases, and contains a potential "GS
      domain," suggesting it is a divergent member of the type I receptor subfamily.
      This receptor is expressed on the surface of the parasite's syncytial tegument
      and expression of receptor messenger RNA and protein is up-regulated following
      infection of the mammalian host. The receptor protein can be isolated in a
      phosphorylated form from adult parasites, which together with its surface
      location, suggests that it functions in transducing signals across the parasite
      surface membrane.

PMID- 9556615
TI  - Identification and characterization of an unusual double serine/threonine protein
      phosphatase 2C in the malaria parasite Plasmodium falciparum.
AB  - We have cloned a gene from Plasmodium falciparum with homology to the Mg2+
      dependent serine/threonine protein phosphatase 2C (PP2C) family. The predicted
      coding region is 920 amino acids long, twice the size of other members of this
      family. We show that this protein can be divided into two halves (Pf2C-1 and Pf2C
      2), each a complete phosphatase unit with homology to other phosphatases of this
      class. To study the function of this PP2C, we have tested the ability of
      different constructs to complement conditional null mutants of yeast. Our results
      show that expression of the full-length protein, the first half alone, the second
      half alone, or a hybrid with the N terminus of the first half and the C terminus
      of the second half was able to complement the heat shock response defect of a
      Schizosaccharomyces pombe strain with a PP2C (PTC1) deletion. Recombinant P.
      falciparum PP2C expressed in Escherichia coli was active in dephosphorylating 32P
      labeled casein in an Mg2+- or Mn2+-dependent reaction. Each half alone was also
      active in recombinant form. Using the two-hybrid system, we have shown that the
      two halves can interact. Gel filtration assay of P. falciparum protein extracts
      suggests that full-length PfPP2C is a dimer, and phosphatase activity competition
      experiments indicate that dimerization of PfPP2C is required for its optimal
      activity. This unusual phosphatase molecule appears to be composed of four
      catalytic units on two polypeptide chains.

PMID- 9556616
TI  - Protein kinase B and rac are activated in parallel within a phosphatidylinositide
      3OH-kinase-controlled signaling pathway.
AB  - The GTPase Rac and the protein kinase B (PKB) are downstream targets of
      phosphatidylinositide 3OH-kinase in platelet-derived growth factor-stimulated
      signaling pathways. We have generated PAE cell lines inducibly expressing mutants
      of Rac. Use of these cell lines suggests that Rac is involved in both platelet
      derived growth factor-stimulated membrane ruffling and the activation of p70(S6K)
      but not in the activation of PKB. Furthermore, expression of constitutively
      active alleles of PKB in PAE cells suggests that PKB is able to regulate the
      activity of p70(S6K) but not the cytoskeletal changes underlying membrane
      ruffling. Thus, our results indicate that Rac and PKB are on separate pathways
      downstream of phosphatidylinositide 3OH-kinase in these cells but that both of
      these pathways are involved in the regulation of p70(S6K).

PMID- 9556617
TI  - Activation of gene expression by a ligand-induced conformational change of a
      protein-DNA complex.
AB  - IlvY protein binds cooperatively to tandem operator sites in the divergent,
      overlapping, promoter-regulatory region of the ilvYC operon of Escherichia coli.
      IlvY positively regulates the expression of the ilvC gene in an inducer-dependent
      manner and negatively regulates the transcription of its own divergently
      transcribed structural gene in an inducer-independent manner. Although binding of
      IlvY protein to the tandem operators is sufficient to repress ilvY promoter
      specific transcription, it is not sufficient to activate transcription from the
      ilvC promoter. Activation of ilvC promoter-specific transcription requires the
      additional binding of a small molecule inducer to the IlvY protein-DNA complex.
      The binding of inducer to IlvY protein does not affect the affinity of IlvY
      protein for the tandem operator sites. It does, however, cause a conformational
      change of the IlvY protein-DNA complex, which is correlated with the partial
      relief of an IlvY protein-induced bend of the DNA helix in the ilvC promoter
      region. This structural change in the IlvY protein-DNA complex results in a 100
      fold increase in the affinity of RNA polymerase binding at the ilvC promoter
      site. The ability of a protein to regulate gene expression by ligand-responsive
      modulation of a protein-DNA structure is an emerging theme in gene regulation.

PMID- 9556618
TI  - A multifunctional repeated motif is present in human bifunctional tRNA
      synthetase.
AB  - Tandem repeats located in the human bifunctional glutamyl-prolyl-tRNA synthetase
      (EPRS) have been found in many different eukaryotic tRNA synthetases and were
      previously shown to interact with another distinct repeated motifs in human
      isoleucyl-tRNA synthetase. Nuclear magnetic resonance and differential scanning
      calorimetry analyses of an isolated EPRS repeat showed that it consists of a
      helix-turn-helix with a melting temperature of 59 degrees C. Specific interaction
      of the EPRS repeats with those of isoleucyl-tRNA synthetase was confirmed by in
      vitro binding assays and shown to have a dissociation constant of approximately
      2.9 microM. The EPRS repeats also showed the binding activity to the N-terminal
      motif of arginyl-tRNA synthetase as well as to various nucleic acids, including
      tRNA. Results of the present work suggest that the region comprising the repeated
      motifs of EPRS provides potential sites for interactions with various biological
      molecules and thus plays diverse roles in the cell.

PMID- 9556619
TI  - Mutations in the double-stranded RNA-activated protein kinase insert region that
      uncouple catalysis from eIF2alpha binding.
AB  - The interferon-induced, double-stranded RNA (dsRNA)-activated protein kinase,
      PKR, inhibits protein synthesis via phosphorylation of the alpha subunit of the
      translation initiation factor eIF2. A kinase insert region N-terminal of PKR
      kinase subdomain V, which is conserved among eIF2alpha kinases, has been proposed
      to determine substrate specificity of these kinases. To investigate the function
      of this kinase insert region, selective PKR mutants were generated, and kinase
      activities and eIF2alpha affinities were analyzed in vitro. The in vivo function
      was investigated by growth inhibitory assays in yeast and translational assays in
      COS cells. Among the 13 mutations, 5 lost kinase activity and 3 exhibited less
      than 30% of wild-type eIF2alpha binding activity. The deletion of the conserved
      sequence (amino acids 362-370) resulted in a protein that had no kinase activity
      and only about 25% of wild-type eIF2alpha binding, suggesting that this sequence
      is not only required for PKR kinase activity but also is important for substrate
      interaction. It was determined that the hydrophobicity of the conserved sequence
      of PKR is required for kinase activity but is not crucial for eIF2alpha binding.
      The amino acid residue Glu-367 in the conserved motif was shown to be directly
      involved in substrate binding but was not important for kinase activity. These
      results suggest that the activation of PKR is not a prerequisite for its binding
      to the substrate and that the conserved motif in subdomain V contributes to the
      interaction of PKR and eIF2alpha.

PMID- 9556620
TI  - Protein C inhibitor secreted from activated platelets efficiently inhibits
      activated protein C on phosphatidylethanolamine of platelet membrane and
      microvesicles.
AB  - Protein C inhibitor (PCI) was detected in human platelets (2.9 ng/10(9) cells)
      and megakaryocytic cells (1.5 ng/10(6) cells). PCI mRNA was also detected in both
      platelets and megakaryocytic cells using nested polymerase chain reaction. PCI
      was found to be located in the alpha-granules of resting platelets. Approximately
      30% of the total amount of PCI in platelets was released after stimulation with
      ADP, collagen, adrenalin, thrombin, or thrombin receptor-activating peptide.
      Secreted PCI was detected on the surface of activated platelets and phospholipid
      microvesicles. PCI secreted from thrombin receptor-activating peptide-stimulated
      platelets inhibited activated protein C (APC) efficiently. PCI significantly
      inhibited APC in the presence of phospholipid vesicles prepared using rabbit
      brain cephalin (RBC) or a mixture of 40% phosphatidylethanolamine (PE), 20%
      phosphatidylserine (PS), and 40% phosphatidylcholine (PC) with a second order
      rate constant of 1.0 x 10(6) M-1.min-1. Of these phospholipids, PE was critical
      for this inhibition. The dissociation constants of the binding of APC or PCI to
      solid phase phospholipids showed that APC binds more preferably to PE than to RBC
      or PS, and PCI to PE or RBC than to PS or PC. PCI binding to solid phase
      phospholipids depended on the presence of PE. RBC- or PE-bound PCI inhibited APC
      significantly but only weakly the gamma-carboxyglutamic acid domainless APC. The
      gamma-carboxyglutamic acid fragment of protein C suppressed the PCI-mediated
      inhibition of APC on solid phase RBC or PE. Most of the APC.PCI complex formed on
      solid phase RBC or PE was released into the soluble phase. These findings suggest
      that PCI secreted from activated platelets binds preferably to PE of platelet
      membrane and microvesicles and that it inhibits phospholipid-bound APC
      efficiently.

PMID- 9556622
TI  - Comparison of Na-K-Cl cotransporters. NKCC1, NKCC2, and the HEK cell Na-L-Cl
      cotransporter.
AB  - The Na-K-Cl cotransporter (NKCC) mediates the coupled movement of ions into most
      animal cells, playing important roles in maintenance of cell volume and in
      epithelial Cl transport. Two forms of NKCC have been described: NKCC1, the
      "housekeeping" isoform that is also responsible for Cl accumulation in secretory
      epithelial cells, and NKCC2, which mediates apical Na+K+Cl entry into renal
      epithelial cells. Here we examine the kinetic properties of NKCC1, NKCC2, and the
      endogenous HEK-293 cell cotransporter. Stable expression of rabbit NKCC2A was
      obtained in HEK-293 cells utilizing a chimera (h1r2A0.7) in which the 5'
      untranslated region and cDNA encoding 104 amino acids of the N terminus are
      replaced by the corresponding sequence of NKCC1. h1r2A0.7 exhibits Na and Cl
      affinities near those of NKCC1, but it has a 4-fold lower Rb affinity, and a 3
      fold higher affinity for the inhibitor bumetanide. The activity of h1r2A0.7 is
      increased on incubation in low [Cl] media as is NKCC1, but the resting level of
      activity is higher in h1r2A0.7 and activation is more rapid. h1r2A0.7 exhibits an
      appropriate volume response, unlike NKCC1 for which concomitant changes in [Cl]i
      appear to be the overriding factor. These results support a model in which apical
      NKCC2 activity is matched to basolateral Cl exit through changes in [Cl]i.
      Reverse transcriptase-polymerase chain reaction of HEK-293 cell mRNA is positive
      with NKCC1 primers and negative with NKCC2 primers. Surprisingly, we found that
      the behavior of the endogenous HEK cell Na-K-Cl cotransporter is unlike either of
      the two forms which have been described: compared with NKCC1, HEK cell
      cotransporter has a 2.5-fold lower Na affinity, an 8-fold lower Rb affinity, and
      a 4-fold higher bumetanide affinity. These results suggest the presence of a
      novel isoform of NKCC in HEK-293 cells.

PMID- 9556621
TI  - Activation of ErbB4 by the bifunctional epidermal growth factor family hormone
      epiregulin is regulated by ErbB2.
AB  - Epiregulin (EPR) is a recently described member of the epidermal growth factor
      (EGF) family of peptide growth factors. The ever expanding size of the EGF family
      has made distinguishing the activities of these hormones paramount. We show here
      that EPR activates two members of the ErbB family of receptor tyrosine kinases,
      epidermal growth factor receptor (EGFR) and ErbB4. Therefore by these criteria,
      EPR is qualitatively similar to another EGF family hormone, betacellulin (BTC).
      Yet, here we also demonstrate quantitative differences between EPR and BTC. EPR
      stimulates higher levels of EGFR phosphorylation than does BTC, whereas BTC
      stimulates higher levels of ErbB4 phosphorylation than does EPR. Moreover, the
      EPR and BTC dose response curves show that although EGFR is more sensitive to EPR
      than is ErbB4, ErbB4 is more sensitive to BTC than is EGFR. Finally, ErbB2, which
      is not activated by EPR when expressed on its own, increases the sensitivity of
      ErbB4 for activation by EPR. Therefore, these results establish that EPR exhibits
      novel activities and modes of regulation, which may have significant implications
      for EPR function in vivo.

PMID- 9556623
TI  - Membrane association of active plasmid partitioning protein A in Escherichia
      coli.
AB  - QsopA and SopA, proteins essential for stable maintenance of low copy number
      plasmids and encoded on plasmid QpH1 of Coxiella burnetii and the F plasmid of
      Escherichia coli, respectively, are shown to be membrane associated using three
      independent approaches: isolation of hybrid protein A-PhoA proteins that display
      PhoA (bacterial alkaline phosphatase) activity indicating a periplasmic location,
      biochemical fractionation by flotation gradient centrifugation, and subcellular
      localization by immunoelectron microscopy. These data provide insight into the
      mechanism by which partitioning protein A spatially directs plasmids into
      daughter cells at bacterial division.

PMID- 9556624
TI  - Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha
      induced cell death.
AB  - Tumor necrosis factor-alpha (TNFalpha)-induced cell death involves a diverse
      array of mediators and regulators including proteases, reactive oxygen species,
      the sphingolipid ceramide, and Bcl-2. It is not known, however, if and how these
      components are connected. We have previously reported that GSH inhibits, in
      vitro, the neutral magnesium-dependent sphingomyelinase (N-SMase) from Molt-4
      leukemia cells. In this study, GSH was found to reversibly inhibit the N-SMase
      from human mammary carcinoma MCF7 cells. Treatment of MCF7 cells with TNFalpha
      induced a marked decrease in the level of cellular GSH, which was accompanied by
      hydrolysis of sphingomyelin and generation of ceramide. Pretreatment of cells
      with GSH, GSH-methylester, or N-acetylcysteine, a precursor of GSH biosynthesis,
      inhibited the TNFalpha-induced sphingomyelin hydrolysis and ceramide generation
      as well as cell death. Furthermore, no significant changes in GSH levels were
      observed in MCF7 cells treated with either bacterial SMase or ceramide, and GSH
      did not protect cells from death induced by ceramide. Taken together, these
      results show that GSH depletion occurs upstream of activation of N-SMase in the
      TNFalpha signaling pathway. TNFalpha has been shown to activate at least two
      groups of caspases involved in the initiation and "execution" phases of
      apoptosis. Therefore, additional studies were conducted to determine the
      relationship of GSH and the death proteases. Evidence is provided to demonstrate
      that depletion of GSH is dependent on activity of interleukin-1beta-converting
      enzyme-like proteases but is upstream of the site of action of Bcl-2 and of the
      execution phase caspases. Taken together, these studies demonstrate a critical
      role for GSH in TNFalpha action and in connecting major components in the
      pathways leading to cell death.

PMID- 9556625
TI  - Evidence for in situ and in vitro association between beta-dystroglycan and the
      subsynaptic 43K rapsyn protein. Consequence for acetylcholine receptor clustering
      at the synapse.
AB  - The accumulation of dystrophin and associated proteins at the postsynaptic
      membrane of the neuromuscular junction and their co-distribution with nicotinic
      acetylcholine receptor (AChR) clusters in vitro suggested a role for the
      dystrophin complex in synaptogenesis. Co-transfection experiments in which alpha-
      and beta-dystroglycan form a complex with AChR and rapsyn, a peripheral protein
      required for AChR clustering (Apel, D. A., Roberds, S. L., Campbell, K. P., and
      Merlie, J. P. (1995) Neuron 15, 115-126), suggested that rapsyn functions as a
      link between AChR and the dystrophin complex. We have investigated the
      interaction between rapsyn and beta-dystroglycan in Torpedo AChR-rich membranes
      using in situ and in vitro approaches. Cross-linking experiments were carried out
      to study the topography of postsynaptic membrane polypeptides. A cross-linked
      product of 90 kDa was labeled by antibodies to rapsyn and beta-dystroglycan; this
      demonstrates that these polypeptides are in close proximity to one another.
      Affinity chromatography experiments and ligand blot assays using rapsyn
      solubilized from Torpedo AChR-rich membranes and constructs containing beta
      dystroglycan C-terminal fragments show that a rapsyn-binding site is present in
      the juxtamembranous region of the cytoplasmic tail of beta-dystroglycan. These
      data point out that rapsyn and dystroglycan interact in the postsynaptic membrane
      and thus reinforce the notion that dystroglycan could be involved in
      synaptogenesis.

PMID- 9556626
TI  - Two E-boxes are the focal point of muscle-specific skeletal muscle type 1 Na+
      channel gene expression.
AB  - We have characterized a group of cis-regulatory elements that control muscle
      specific expression of the rat skeletal muscle type 1 sodium channel (SkM1) gene.
      These elements are located within a 3. 1-kilobase fragment that encompasses the
      5'-flanking region, first exon, and part of the first intron of SkM1. We
      sequenced the region between -1062 and +311 and determined the start sites of
      transcription; multiple sites were identified between +1 and +30. The basal
      promoter (-65/+11) lacks cell-type specificity, while an upstream repressor (
      174/-65) confers muscle-specific expression. A positive element (+49/+254)
      increases muscle-specific expression. Within these broad elements, two E boxes
      play a pivotal role. One E box at -31/-26 within the promoter, acting in part
      through its ability to bind the myogenic basic helix-loop-helix proteins,
      recruits additional factor(s) that bind elsewhere within the SkM1 sequence to
      control positive expression of the gene. A second E box at -90/-85 within the
      repressor controls negative regulation of the gene and acts through a different
      complex of proteins. Several of these cis-regulatory elements share both sequence
      and functional similarities with cis-regulatory elements of the acetylcholine
      receptor delta-subunit; the different arrangement of these elements may
      contribute to unique expression patterns for the two genes.

PMID- 9556627
TI  - Characterization of an 88-kDa heat shock protein of Neurospora crassa that
      interacts with Hsp30.
AB  - The small heat shock protein of Neurospora crassa, Hsp30, when employed in
      affinity chromatography, bound two cellular proteins that were identified as
      Hsp70 and Hsp88. Both Hsp70 and Hsp88 bound to Hsp30 in preference to other
      proteins, but binding of Hsp88 was more selective for Hsp30, and a direct
      interaction was observed. Transcripts for Hsp88, a newly characterized protein,
      are present at normal temperature, but they are strongly induced by heat shock.
      Its cDNA sequence predicts a protein with homology to mammalian Hsp110 family
      proteins, which are distantly related to Hsp70. Hsp88 and its homologues show
      greater similarity to Hsp70 in its N-terminal ATPase domain than in the C
      terminal peptide-binding domain, and its ATP-binding motifs are conserved.
      Nevertheless, the N-terminal domain of Hsp88 (and related proteins) is
      consistently more hydrophobic and more basic than that of Hsp70 proteins. Within
      the C-terminal domain, the sequence corresponding to the DnaK alpha subdomain is
      conserved in the Hsp88/Hsp110 family proteins, whereas the DnaK beta subdomain
      sequence is not conserved. The interaction between Hsp70 and Hsp30 may reflect
      their cooperation as cochaperones for denatured proteins, whereas Hsp88 and Hsp30
      may form a complex that interacts with potential substrates.

PMID- 9556628
TI  - The hyaluronan receptor RHAMM regulates extracellular-regulated kinase.
AB  - We have identified two RHAMM (receptor for hyaluronan-mediated motility) isoforms
      that encode an alternatively spliced exon 4 (Hall, C. L., Yang, B., Yang, X.,
      Zhang, S., Turley, M., Samuel, S., Lange, L. A., Wang, C., Curpen, G. D., Savani,
      R. C., Greenberg, A. H., and Turley, E. A. (1995) Cell 82, 19-26 and Wang, C.,
      Entwistle, J., Hou, G., Li, Q., and Turley, E. A. (1996) Gene 174, 299-306). One
      of these, RHAMM variant 4 (RHAMMv4), is transforming when overexpressed and
      regulates Ras signaling (Hall et al.). Here we note using flow cytometry and
      confocal analysis that RHAMM isoforms encoding exon 4 occur both on the cell
      surface and in the cytoplasm. Epitope-tagging experiments indicate that RHAMMv4
      occurs only in the cytoplasm. Several observations suggest that both cell surface
      RHAMM isoforms and RHAMMv4 are involved in regulating extracellular-regulated
      kinase (ERK) activity. Affinity-purified anti-RHAMM exon 4 antibodies block the
      ability of platelet-derived growth factor to activate ERK, and these reagents
      modify the protein tyrosine phosphorylation profile of proteins resulting from
      treatment with platelet-derived growth factor. A dominant negative form of
      RHAMMv4 inhibits mutant active Ras activation of ERK and coimmunoprecipitates
      with both mitogen-activated protein kinase kinase and ERK, suggesting that the
      intracellular RHAMMv4 acts downstream of Ras, possibly at the level of mitogen
      activated protein kinase kinase-ERK interactions. Consistent with this,
      overexpression of RHAMMv4 constitutively activates ERK. These results identify a
      novel mechanism for the regulation of the Ras-ERK signaling pathway and suggest
      that RHAMM plays multiple roles in this regulation.

PMID- 9556629
TI  - Characterization of a second member of the sentrin family of ubiquitin-like
      proteins.
AB  - Sentrin is a novel ubiquitin-like protein that can be conjugated to other
      proteins in a manner analogous to ubiquitination. Two additional cDNA sequences
      that encode proteins highly homologous to sentrin have been reported to
      GenBankTM. It is not known whether these sentrin-like proteins could also
      function as protein modifiers. In this report, a second member of the sentrin
      family was characterized in detail. Sentrin-2 is a 95-amino acid polypeptide that
      is 46% identical and 66% homologous to sentrin-1. Northern blot analysis showed
      that the sentrin-2 message was expressed in all tissues, but was barely
      detectable in the liver and placenta. The ability of sentrin-2 to conjugate to
      other proteins was tested by expressing hemagglutinin epitope-tagged sentrin-2 in
      COS cells. Western blot analysis showed that sentrin-2 could be transferred to
      other proteins in a pattern similar to that of sentrin-1 conjugation and had
      similar C-terminal processing. We further showed that both sentrin-1 and sentrin
      2 could covalently modify RanGAP1, a Ran GTPase-activating protein critically
      involved in nuclear transport. Immunocytochemical analysis showed that sentrin-2
      derivatives were highly enriched in the nucleus. Taken together, our results
      demonstrate that sentrin-2 is another protein modifier for the sentrinization
      pathway.

PMID- 9556630
TI  - Fluoroaluminate induces activation and association of Src and Pyk2 tyrosine
      kinases in osteoblastic MC3T3-E1 cells.
AB  - Fluoride is known to increase bone mass in vivo, probably through stimulation of
      osteoblast proliferation; however, the mechanisms of fluoroaluminate action in
      osteoblasts have not yet been elucidated. We have previously shown that in
      osteoblastic MC3T3-E1 cells, fluoroaluminate stimulates G protein-mediated
      protein tyrosine phosphorylation (Scaronuscarona, M., Standke, G. J. R., Jeschke,
      M., and Rohner, D. (1997) Biochem. Biophys. Res. Commun. 235, 680-684). Although
      the Ser/Thr kinases Erk1, Erk2, and p70(S6K) were activated in response to
      fluoroaluminate, the identity of fluoroaluminate-activated tyrosine kinase(s)
      remained elusive. In this study, we show that in MC3T3-E1 cells, fluoroaluminate
      induces a 110-kDa tyrosine-phosphorylated protein that we identify as Pyk2, a
      cytoplasmic tyrosine kinase related to Fak (focal adhesion kinase). The tyrosine
      phosphorylation of Pyk2 increased in a dose- and time-dependent manner. The
      autophosphorylation activity of Pyk2 increased 3-fold and reached its maximum
      within 10 min of fluoroaluminate treatment. Fluoroaluminate also induced
      activation of Src and the association of Pyk2 with Src. The phosphorylation of
      Src-associated Pyk2 increased >20-fold in in vitro kinase assays, suggesting that
      Pyk2 is phosphorylated by Src. Although MC3T3-E1 cells express much more Fak than
      Pyk2, Src preferentially associated with Pyk2. In vitro, Pyk2 bound to the Src
      SH2 domain, suggesting that this interaction mediates the Src-Pyk2 association in
      cells. These data indicate that osteoblastic cells express Pyk2, which is
      tyrosine-phosphorylated and activated in response to G protein activation by
      fluoroaluminate, and that the mechanism of Pyk2 activation most likely involves
      Src. Thus, Src and Pyk2 are tyrosine kinases involved in G protein-mediated
      tyrosine phosphorylation in osteoblastic cells and may be important for the
      osteogenic action of fluoroaluminate.

PMID- 9556631
TI  - Acceleration of myosin light chain dephosphorylation and relaxation of smooth
      muscle by telokin. Synergism with cyclic nucleotide-activated kinase.
AB  - Incorporation of 32P into telokin, a smooth muscle-specific, 17-18-kDa, acidic
      (pI 4.2-4.4) protein, was increased by forskolin (20 microM) in intact rabbit
      ileum smooth muscle (ileum) and by 8-bromo-cyclic GMP (100 microM) in alpha-toxin
      permeabilized ileum. Native telokin (5-20 microM), purified from turkey gizzard,
      and recombinant rabbit telokin, expressed in Escherichia coli and purified to
      >90% purity, induced dose-dependent relaxation, associated with a significant
      decrease in regulatory myosin light chain phosphorylation, without affecting the
      rate of thiophosphorylation of regulatory myosin light chain of ileum
      permeabilized with 0.1% Triton X-100. Endogenous telokin was lost from ileum
      during prolonged permeabilization (>20 min) with 0.1% Triton X-100, and the time
      course of loss was correlated with the loss of 8-bromo-cyclic GMP-induced calcium
      desensitization. Recombinant and native gizzard telokins were phosphorylated, in
      vitro, by the catalytic subunit of cAMP-dependent protein kinase, cGMP-dependent
      protein kinase, and p42/44 mitogen-activated protein kinase; the recombinant
      protein was also phosphorylated by calmodulin-dependent protein kinase II.
      Exogenous cGMP-dependent protein kinase (0.5 microM) activated by 8-bromo-cyclic
      GMP (50 microM) phosphorylated recombinant telokin (10 microM) when added
      concurrently to ileum depleted of its endogenous telokin, and their relaxant
      effects were mutually potentiated. Forskolin (20 microM) also increased
      phosphorylation of telokin in intact ileum. We conclude that telokin induces
      calcium desensitization in smooth muscle by enhancing myosin light chain
      phosphatase activity, and cGMP- and/or cAMP-dependent phosphorylation of telokin
      up-regulates its relaxant effect.

PMID- 9556632
TI  - Protease resistance of syntaxin.SNAP-25.VAMP complexes. Implications for assembly
      and structure.
AB  - A stable ternary complex formed with vesicle-associated membrane protein 2
      (VAMP2) and plasma membrane proteins syntaxin 1A and synaptosome-associated
      protein of 25 kDa (SNAP-25) is proposed to function in synaptic vesicle
      exocytosis. To analyze the structural characteristics of this synaptic protein
      complex, recombinant binary (syntaxin 1A.SNAP-25), recombinant ternary, and
      native ternary complexes were subjected to limited trypsin proteolysis. The
      protected fragments, defined by amino-terminal sequencing and mass spectrometry,
      included a carboxyl-terminal region of syntaxin 1A, the cytoplasmic domain of
      VAMP2, and amino- and carboxyl-terminal regions of SNAP-25. Furthermore, separate
      amino- and carboxyl-terminal fragments of SNAP-25, when combined with VAMP2 and
      syntaxin 1A, were sufficient for stable complex assembly. Analysis of ternary
      complexes formed with full-length proteins revealed that the carboxyl-terminal
      transmembrane anchors of both syntaxin 1A and VAMP2 were protected from trypsin
      digestion. Moreover, the stability of ternary complexes was increased by
      inclusion of these transmembrane domains. These results suggest that the
      transmembrane domains of VAMP2 and syntaxin 1A contribute to complex assembly and
      stability and that amino- and carboxyl-terminal regions of SNAP-25 may function
      as independent domains.

PMID- 9556633
TI  - Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's
      disease and their characterization.
AB  - Hirschsprung's disease (HSCR) is a congenital intestinal disease, characterized
      by the absence of ganglion cells in the distal portion of the intestinal tract.
      Recently, three susceptibility genes have been identified in HSCR, namely the RET
      protooncogene, the endothelin B (ETB) receptor gene (EDNRB), and the endothelin-3
      (ET-3) gene (EDN3). To investigate whether mutations in EDNRB could be related
      with HSCR in non-inbred populations in Japan, we examined alterations of the gene
      in 31 isolated patients. Three novel mutations were detected as follows: two
      transversions, A to T and C to A at nucleotides 311 (N104I) and 1170 (S390R),
      respectively, and a transition, T to C at nucleotide 325 (C109R). To analyze
      functions of these mutant receptors, they were expressed in Chinese hamster ovary
      cells. S390R mutation did not change the binding affinities but caused the
      decreases in the ligand-induced increment of intracellular calcium and in the
      inhibition of adenylyl cyclase activity, showing the impairment of the
      intracellular signaling. C109R receptors were proved to be localized near the
      nuclei as an unusual 44-kDa protein with the extremely low affinity to endothelin
      1 (ET-1) and not to be translocated into the plasma membrane. On the other hand,
      N104I receptors showed almost the same binding affinities and functional
      properties as those of the wild type. Therefore, we conclude that S390R and C109R
      mutations could cause HSCR but that N104I mutation might be polymorphous.

PMID- 9556634
TI  - A trace amount of the human pro-apoptotic factor Bax induces bacterial death
      accompanied by damage of DNA.
AB  - An amount of human pro-apoptotic Bax as low as 0.01% of total protein was
      sufficient to cause cell death in Escherichia coli. The bacterial cell death was
      examined using a viable bacteria-specific fluorescence indicator system and loss
      of colony formation ability. Co-expression of anti-apoptotic Bcl-xL showed a
      modest inhibitory effect on the cell death caused by Bax. The trace amount of Bax
      elongated E. coli and accumulated monounsaturated fatty acids, suggesting an
      unusual metabolism of redox in the host. In fact, an increase of KCN-dependent O2
      consumption accompanied the expression of Bax. At the same time, a fluorescent pH
      indicator showed the apparent accumulation of protons outside the cell,
      suggesting that the membrane is intact. Bax increased the level of superoxide
      anion as measured by the expression of superoxide-dependent promoter. Nicked DNA
      was significantly generated, and the frequency of mutations resistant to
      rifampicin was increased by 30-fold, depending upon the expression of Bax. It is
      proposed that trace amounts of Bax increase oxygen consumption, triggering
      generation of superoxide, which affects DNA, leading to bacterial death.

PMID- 9556635
TI  - Golgi localization and functional expression of human uridine diphosphatase.
AB  - A full-length E(ecto)-ATPase (Plesner, L. (1995) Int. Rev. Cytol. 158, 141-214)
      cDNA was cloned from a human brain cDNA library; it encodes a 610-amino acid
      protein that contains two putative transmembrane domains. Heterologous expression
      of this protein in COS-7 cells caused a significant increase in intracellular
      membrane-bound nucleoside phosphatase activity. The activity was highest with UDP
      as substrate and was stimulated by divalent cations in the following order: Ca2+
      >> Mg2+ > Mn2+. The results of immunofluorescence staining indicate that this
      protein is located in the Golgi apparatus. UDP hydrolysis was increased in the
      presence of Triton X-100 or alamethicin, an ionophore that facilitates movement
      of UDP across the membrane, suggesting that the active site of this UDPase is on
      the luminal side of the Golgi apparatus. This is the first identification of a
      mammalian Golgi luminal UDPase gene. Computer-aided sequence analysis of the
      EATPase superfamily indicates that the human UDPase is highly similar to two
      hypothetical proteins of the nematode Caenorhabditis elegans and to an
      unidentified 71.9-kDa yeast protein and is less related to the previously
      identified yeast Golgi GDPase.

PMID- 9556636
TI  - The calcium channel antagonist controversy.

PMID- 9556638
TI  - Comparing family physicians: Canada and the United States.

PMID- 9556637
TI  - Cookouts and the seasonal peak of Escherichia coli infection.

PMID- 9556639
TI  - Preventing falls in the elderly.

PMID- 9556640
TI  - Down syndrome and incidence of Alzheimer's disease.

PMID- 9556641
TI  - Impact of patient-directed pharmaceutical advertising.

PMID- 9556642
TI  - Hepatitis A vaccination.

PMID- 9556643
TI  - Diagnosis and treatment of prostate cancer.
AB  - In the United States, prostate cancer is the most common solid tumor malignancy
      in men and second to lung cancer as the leading cause of cancer deaths in this
      group. Even though prostate cancer is responsible for 40,000 deaths per year,
      screening programs are a matter of controversy because scientific evidence is
      lacking that early detection decreases morbidity and mortality. Furthermore,
      treatment decisions are difficult to make because of the generally indolent
      nature of prostate cancer and because it tends to occur in older men who often
      have multiple, competing medical illnesses. Depending on the specific situation,
      radical prostatectomy, radiotherapy or watchful waiting (observation) will be the
      most appropriate management option. In general, localized cancer is best treated
      with surgical removal of the prostate gland or radiotherapy. Hormone deprivation
      therapy is the primary method of controlling metastatic prostate cancer. At
      present, chemotherapy cannot cure disseminated prostate cancer. Watchful waiting
      is a reasonable management alternative for prostate cancer in an older patient or
      a patient with other serious illnesses.

PMID- 9556644
TI  - Calcium channel antagonists: morbidity and mortality--what's the evidence?
AB  - Recent studies have shown an association between the use of calcium channel
      antagonists for the treatment of hypertension and an increased risk of myocardial
      infarction, gastrointestinal hemorrhage and cancer. The interpretation of the
      results of these studies and their application to clinical practice requires an
      understanding of study design constraints, conflicting results and limitations in
      extrapolating study findings to other dosage strengths, formulations or agents
      within the calcium channel antagonist class. A review and critique of these
      studies provides background information on the controversial subject of using
      calcium channel antagonists for the treatment of hypertension. Despite the
      limitations of these studies, clinicians may want to select other classes of
      agents, including diuretics and beta blockers, as first-line therapy until the
      morbidity and mortality effects related to the use of calcium channel antagonists
      are clearly known.

PMID- 9556646
TI  - Evaluation and treatment of urinary tract infections in children.
AB  - Urinary tract infections (UTIs) are among the most common bacterial infections
      encountered by primary care physicians. Although UTIs do not occur with as great
      a frequency in children as in adults, they can be a source of significant
      morbidity in children. For reasons that are not yet completely understood, a
      minority of UTIs in children progress to renal scarring, hypertension and renal
      insufficiency. Clinical presentation of UTI in children may be nonspecific, and
      the appropriateness of certain diagnostic tests remains controversial. The
      diagnostic work-up should be tailored to uncover functional and structural
      abnormalities such as dysfunctional voiding, vesicoureteral reflux and
      obstructive uropathy. A more aggressive work-up, including renal cortical
      scintigraphy, ultrasound and voiding cystourethrography, is recommended for
      patients at greater risk for pyelonephritis and renal scarring, including infants
      less than one year of age and all children who have systemic signs of infection
      concomitant with a UTI. Antibiotic prophylaxis is used in patients with reflux or
      recurrent UTI who are at greater risk for subsequent infections and
      complications.

PMID- 9556645
TI  - SIDS: counseling parents to reduce the risk.
AB  - Although the cause or causes of sudden infant death syndrome (SIDS) remain
      unknown, the incidence of SIDS is on the decline in the United States and other
      countries. This decline has been accomplished largely through public education
      campaigns informing parents about several important factors associated with an
      increased risk of SIDS. These factors are prone and side infant sleeping
      positions, exposure of infants to cigarette smoke and potentially hazardous
      sleeping environments. Risk-reduction measures such as placing healthy infants to
      sleep in the supine position, avoiding passive smoke exposure both before and
      after birth and optimizing crib safety are beginning to lower the SIDS rate in
      this country. Through patient education, family physicians can further reduce the
      incidence of the number one cause of death in infants one week to one year old.

PMID- 9556647
TI  - Management of seizures and epilepsy.
AB  - While the evaluation and treatment of patients with seizures or epilepsy is often
      challenging, modern therapy provides many patients with complete seizure control.
      After a first seizure, evaluation should focus on excluding an underlying
      neurologic or medical condition, assessing the relative risk of seizure
      recurrence and determining whether treatment is indicated. Successful management
      of patients with recurrent seizures begins with the establishment of an accurate
      diagnosis of epilepsy syndrome followed by treatment using an appropriate
      medication in a manner that optimizes efficacy. The goal of therapy is to
      completely control seizures without producing unacceptable medication side
      effects. Patients who do not achieve complete seizure control should be referred
      to an epilepsy specialist, since new medications and surgical treatments offer
      patients unprecedented options in seizure control.

PMID- 9556648
TI  - Office management of Bartholin gland cysts and abscesses.
AB  - Bartholin gland cysts and abscesses are common problems in women of reproductive
      age. Although the cysts are usually asymptomatic, they may become enlarged or
      infected and cause significant pain. Often the clinician is tempted simply to
      lance the cyst or abscess, since this technique can be effective for other common
      abscesses. However, simple lancing of a Bartholin gland cyst or abscess may
      result in recurrence. More effective treatment methods include use of a Word
      catheter and marsupialization, both of which can be performed in the office.

PMID- 9556649
TI  - Recognition and treatment of obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder is relatively common; however, its actual incidence
      has only recently become clear. The neurotransmitter serotonin appears to have a
      central role in this disorder. Males and females are affected equally, with onset
      usually occurring in late adolescence. Symptoms include intrusive thoughts that
      lead the patient to perform repetitive rituals that interfere with daily living.
      Although patients are typically distressed by these thoughts and rituals, they
      seldom volunteer their symptoms. Successful diagnosis often requires specific
      questioning by the physician. Treatment is directed at symptom reduction;
      however, complete remission of symptoms is unusual. Pharmacologic therapy usually
      includes clomipramine or antidepressant treatment with selective serotonin
      reuptake inhibitors, but in dosage ranges higher than those typically used in the
      treatment of depression. Behavior therapy has also been proved effective, both
      alone and in conjunction with pharmacologic therapy.

PMID- 9556650
TI  - Photo quiz. Projections on the glans penis.

PMID- 9556651
TI  - American Heart Association issues guidelines on imaging in transient ischemic
      attacks and stroke.

PMID- 9556652
TI  - ACOG issues report on the management of post-term pregnancy. American College of
      Obstetricians and Gynecologists.

PMID- 9556653
TI  - AIDS in persons 50 years of age and older.

PMID- 9556654
TI  - Extensive restriction site polymorphism at the human phenylalanine hydroxylase
      locus and application in prenatal diagnosis of phenylketonuria.
AB  - A total of 10 restriction site polymorphisms have been identified at the human
      phenylalanine hydroxylase locus using a full-length human phenylalanine
      hydroxylase cDNA clone as a hybridization probe to analyze human genomic DNA.
      These polymorphic patterns segregate in a Mendelian fashion and concordantly with
      the disease state in various PKU kindreds. The frequencies of the restriction
      site polymorphisms at the human phenylalanine hydroxylase locus among Caucasians
      are such that the observed heterozygosity in the population is 87.5%. Thus, most
      families with a history of classical phenylketonuria can take advantage of the
      genetic analysis for prenatal diagnosis and carrier detection of the hereditary
      disorder.

PMID- 9556655
TI  - A systematic approach for detecting high-frequency restriction fragment length
      polymorphisms using large genomic probes.
AB  - Thirteen phage clones containing low-copy sequences were isolated from a human
      DNA library and tested for their ability to detect restriction fragment length
      polymorphisms (RFLPs). Reported are the RFLPs revealed with each clone, all found
      in frequencies useful for linkage studies. Cytological data are available for
      five of the 13 clones, with regional assignments made for three of the markers by
      in situ hybridization. It is concluded that phage clones containing large unique
      DNA inserts detect multiple RFLPs with high efficiency. An analysis of the
      relative efficiency of 20 restriction enzymes for detecting single nucleotide
      changes is discussed by comparing the observed data to those expected on the
      basis of recognition and potential site frequencies, as computed from the
      dinucleotide distribution. Finally, in an effort to facilitate linkage studies
      using polymorphic DNA sequences, experiments were made with pools of probes from
      various sources.

PMID- 9556657
TI  - Monoclonal antibodies to coagulation factor IX define a high-frequency
      polymorphism by immunoassays.
AB  - Monoclonal antibodies have been used to demonstrate a polymorphism of human
      plasma coagulation factor IX antigen in double antibody solid-phase
      immunoradiometric assays. This polymorphism is detected in an assay where a
      monoclonal antibody (A-1) adsorbed to microtiter wells is used to bind factor IX
      from diluted plasma samples. Plasma samples with the factor IX polymorphism have
      less than 0.2 U/ml of apparent antigen when tested with the A-1 antibody, while
      assays with other monoclonal antibodies and assays with goat antisera to factor
      IX show normal amounts of factor IX antigen. Factor IX coagulant activity was
      normal in samples from donors with the polymorphism. The thin-layer
      polyacrylamide gel isoelectric focusing pattern of factor IX purified from a
      donor with the factor IX polymorphism (IXp) was identical to that obtained with
      factor IX prepared from a donor who did not have the polymorphism (IXn). Purified
      radiolabeled factor IX prepared from a donor with the polymorphism showed a Ka
      for the A-1 antibody that was threefold less than that measured for IXn. The gene
      frequency of IXp in male blood donors is 0.25. This polymorphism may be useful as
      a marker for the X chromosome in genetic studies on plasma samples. Further
      studies are necessary to determine the explanation for decreased reaction of IXp
      with the A-1 monoclonal antibody.

PMID- 9556656
TI  - High frequency of nonclassical steroid 21-hydroxylase deficiency.
AB  - Nonclassical steroid 21-hydroxylase deficiency is an autosomal recessive disorder
      that is defined by clinical and hormonal criteria that distinguishes it from the
      classical 21-hydroxylase deficiency. No estimates of the gene frequency of
      nonclassical 21-hydroxylase deficiency, also called attenuated, late-onset,
      acquired, and cryptic adrenal hyperplasia, have been published thus far. Here, we
      have used HLA-B genotype data in families containing multiple members affected
      with nonclassical 21-hydroxylase deficiency together with the results of
      quantitative hormonal tests to arrive at estimates of gene and disease
      frequencies for this disorder. We found nonclassical 21-hydroxylase deficiency to
      be a far more common disorder than classical 21-hydroxylase deficiency, which
      occurs in 1/8,000 births. The prevalence of the disease in Ashkenazi Jews was
      3.7%; in Hispanics, 1.9%; in Yugoslavs, 1.6%; in Italians, 0.3%; and in the
      diverse Caucasian population, 0.1%. The gene for nonclassical 21-hydroxylase
      deficiency is in genetic linkage disequilibrium with HLA-B14 in Ashkenazi Jews,
      Hispanics, and Italians, but not in Yugoslavs or in a diverse, non-Jewish,
      Caucasian group. The penetrance of nonclassical 21-hydroxylase deficiency gene in
      the HLA-B14 containing haplotypes was incomplete. Thus, nonclassical 21
      hydroxylase deficiency is probably the most frequent autosomal recessive genetic
      disorder in man and is especially frequent in Ashkenazi Jews, Hispanics,
      Italians, and Yugoslavs.

PMID- 9556658
TI  - Segregation analysis of hemophilia A and B.
AB  - We analyzed a sample of 1,485 families with hemophilia A and B and with unknown
      diagnosis. The frequency of sporadic cases was estimated to be .166 and .078 for
      the two types of hemophilia, respectively. The sex ratio of mutation rates did
      not differ significantly from unity. The average age of maternal grandfathers of
      probands at birth of mothers with a single child, affected by hemophilia B, and
      of maternal grandfathers of probands at birth of mothers with more than one child
      affected by hemophilia B, was higher than the age in appropriate control groups.

PMID- 9556659
TI  - Genetic analysis of idiopathic hemochromatosis using both qualitative (disease
      status) and quantitative (serum iron) information.
AB  - An ongoing family study of idiopathic hemochromatosis in Brittany, France,
      allowed us to investigate the segregation of this trait and its linkage and
      association to the HLA-A locus in 147 pedigrees, comprising 1,408 individuals
      with over 900 characterized for relevant biological parameters and typed for HLA.
      The joint consideration of affection status and serum iron concentration reveals
      no dominance effect on the latter trait and documents the increased information
      afforded by the consideration of a biological correlate of liability to affection
      for disease exhibiting incomplete penetrance. Our overall results are in general
      agreement with published results on a Utah family study.

PMID- 9556660
TI  - Analysis of three restriction fragment length polymorphisms in the human type II
      procollagen gene.
AB  - Cloned genomic DNA sequences corresponding to various regions of the human type
      II procollagen gene were used to analyze the DNA from 78 normal volunteers.
      Southern hybridization experiments detected polymorphic HindIII, BamHI, and EcoRI
      sites. The presence of the polymorphic HindIII site results in a 7.0-kilobase
      (kb) band, and the absence of this site results in a 14.0-kb band. When present,
      the BamH1 polymorphic site yields a 4.8-kb band, and when absent, yields a 7.2-kb
      band. The presence of the EcoRI polymorphic site results in a 3.7-kb band, and
      its absence results in a 7.0-kb band. Each polymorphic site was mapped. Analyses
      of the data demonstrated that the sites are present in overall gene frequencies
      of .39 for HindIII, .04 for BamHI, and .02 for EcoRI. Gene frequencies of the
      polymorphic sites were also studied with respect to race. The polymorphic sites
      are present in a Hardy-Weinberg distribution in the study population. Study of an
      extended family demonstrated that the segregation of the HindIII polymorphic site
      is consistent with Mendelian inheritance.

PMID- 9556661
TI  - Diagnosis and carrier detection of Tay-Sachs disease: direct determination of
      hexosaminidase A using 4-methylumbelliferyl derivatives of beta-N
      acetylglucosamine-6-sulfate and beta-N-acetylgalactosamine-6-sulfate.
AB  - 4-Methylumbelliferyl-6-sulfo-2-acetamido-2-deoxy derivatives of beta-D
      glucopyranoside and beta-D-galactopyranoside were prepared by direct sulfation of
      the commonly used unsulfated derivatives. Both sulfated substrates were highly
      specific for hexosaminidase A, and in fractionated serum, cells, and tissue
      preparations, less than 2.5% of these activities were associated with
      hexosaminidase B and the intermediate isozyme fractions. Serum and leukocytes
      from patients with infantile Tay-Sachs disease, including a patient with
      thermolabile hexosaminidase B, had less than 2% of noncarrier activities. Carrier
      values were clearly separated from those of noncarriers, and no problems were
      encountered in utilizing sera from pregnant women. The % hexosaminidase A values
      as derived from the ratio between the activities toward the sulfated and
      unsulfated substrates in the same specimen were comparable to those obtained by
      the heat-inactivation method (except for subjects with thermolabile
      hexosaminidase B) and may be helpful in genotype determination in borderline
      cases.

PMID- 9556662
TI  - Assignment of the gene for human sphingolipid activator protein-2 (SAP-2) to
      chromosome 10.
AB  - Sphingolipid activator protein-2 (SAP-2) has been found to stimulate the
      enzymatic hydrolysis of glucosylceramide, galactosylceramide, and sphingomyelin.
      When human skin fibroblast extracts were subjected to sodium dodecylsulfate
      polyacrylamide gel electrophoresis followed by electroblotting and immunochemical
      staining using monospecific antibodies against SAP-2, two or three major bands
      with estimated mol. wts. of 9,000-10,000 were found. These antibodies did not
      crossreact with purified SAP-1, another activating protein, or with extracts of
      CHO-K1 cells. A series of 22 human/Chinese hamster ovary cell hybrids containing
      different human chromosomes were examined by this method. All eight hybrid clones
      containing human chromosome 10 were found to have crossreacting protein in this
      region. Other chromosomes could be excluded by this method. From these results,
      we conclude that the gene coding for human SAP-2 is located on chromosome 10.

PMID- 9556663
TI  - The presence of at least two different H-blood-group-related beta-D-gal alpha-2-L
      fucosyltransferases in human serum and the genetics of blood group H substances.
AB  - Sera from H normal, secretors and nonsecretors (H/-, Se/- and H/-, se/se), as
      well as from H-deficient secretors (h/h, Se/- or Bombay secretors) contain
      enzyme(s) for the transfer of L-fucose in the alpha-configuration to the 2
      position of suitable beta-D-galactopyranosyl units. Sera from H-deficient
      nonsecretors (h/h, se/se; i.e., Bombay nonsecretors) are devoid of such beta-D
      Gal alpha-2-L-fucosyltransferase(s). In order to study these enzymes, a
      comparison was made of the kinetic properties of the enzymes present in the sera
      of H-normal nonsecretors (H/-, se/se) with those of H-deficient secretors (h/h,
      Se/se) with those of H-deficient secretors (h/h, Se/-). These studies revealed a
      clear difference between the two sources of enzyme: (1) the apparent Km for GDP
      fucose was four times lower with the H-normal nonsecretor serum (0.008 mM) than
      with the H-deficient secretor serum (0.028 mM); (2) acceptors with a type 1 or
      type 3 chain proved to be better than acceptors with a type 2 chain or than
      phenyl-beta-D-galactopyranoside for the enzyme present in the serum of H
      deficient secretor individuals. Indeed, the synthetic type 2 compound, betaDGal
      (1-->4)-3-deoxy-beta-DGlcNAc-1-OCH3, which cannot act as an acceptor of beta
      DGlcNAc alpha-3/4-L-fucosyltransferases, remained unchanged in the serum of an H
      deficient secretor but was a good acceptor in the serum of an H-normal
      nonsecretor, and (3) the alpha-2-L fucosyltransferease activity of the H
      deficient secretor serum was more sensitive to heat inactivation than that of the
      H-normal nonsecretor serum (t1/2 at 46 degrees C were 10 min and 75 min,
      respectively). These results show that at least two distinct alpha-2-L
      fucosyltransferases are present in human serum. It is concluded that the
      enzymatic activity found in the H-deficient secretor serum (h/h, Se/-) could be
      the product of the Se gene and the enzymatic activity found in the H-normal
      nonsecretor serum (H/-, se/se) could be the product of the H gene. This
      conclusion correlates well with the finding that H and Se genes are closely
      linked and might have derived by gene duplication in the course of evolution.

PMID- 9556664
TI  - HLA antigens, phytohemagglutinin stimulation, and corticosteroid response.
AB  - Although it is clear that the major histocompatibility complex is associated with
      lymphocyte glucocorticoid sensitivity in mice, there has been less evidence for a
      similar relationship in man. We have typed 158 individuals for: (1) 13 A locus
      and 16 B locus antigens, (2) degree of stimulation of their purified lymphocytes
      by phytohemagglutinin A (PHA), and (3) degree of inhibition of the PHA
      stimulation by prednisolone and prednisolone-21-hemisuccinate. In contrasts of
      individuals with a particular antigen (homozygous or heterozygous) with all
      remaining individuals, HLA-B7 was found to be associated with an enhancing effect
      on the log stimulation by PHA while other antigens of these series did not have
      significant associations. In similar contrasts, A10 was associated with a
      decrease in sensitivity to glucocorticoid inhibition of PHA stimulation as
      measured by the log I50 of the suppression of PHA stimulation. Other antigens of
      these series were not found to have significant associations with the
      glucocorticoid sensitivity of lymphocytes in this assay.

PMID- 9556665
TI  - Evidence supporting a single origin of the beta(C)-globin gene in blacks.
AB  - In order to characterize the origin(s) of the beta C-globin gene in blacks, 25
      chromosomes bearing this gene were characterized at eight polymorphic restriction
      sites within the beta-globin gene cluster. Twenty-two of the 25 chromosomes were
      identical at all sites and possessed a haplotype seen only infrequently among
      beta A-bearing chromosomes in black Americans. Two different haplotypes were
      observed among the three exceptional chromosomes. These haplotypes were identical
      to the most common beta C allele in the 3' end of the beta-globin gene cluster,
      but differed in the 5' region. Partial haplotype analysis on an additional 14
      beta C alleles demonstrated complete association with the typical beta C
      associated polymorphisms in the 3' region of the cluster. These data can be most
      easily explained by a single origin of the mutation followed by spread of the
      mutation to other haplotypes through meiotic recombination 5' to the beta-globin
      gene.

PMID- 9556666
TI  - Extremely high frequencies of alpha-globin gene deletion in Madang and on Kar Kar
      Island, Papua New Guinea.
AB  - Extremely high frequencies of the deletion form of alpha(+)-thalassemia (
      alpha/), as studied by the DNA mapping technique, were found in the population of
      Madang, a coastal province in the north of Papua New Guinea (PNG) and in the
      population of Kar Kar, an island situated near Madang. Ninety-seven percent of
      the population tested from Madang and 89% of that from Kar Kar Island were either
      alpha(+)-thalassemia heterozygotes or homozygotes. By contrast, no examples of
      the deletion form were detected in the Eastern Highlands of PNG. The haplotype
      frequencies of alpha(+)-thalassemia (-alpha/) in Madang and Kar Kar Island were
      found to be 81.33% and 66.67%, respectively. A more detailed analysis of the gene
      deletion revealed that in both populations 96% were of the 4.2 kilobase (kb) type
      and 4% were of the 3.7-kb type. Thus, this group is the only example in which the
      4.2-kb deletion is predominant over 3.7-kb defect. The presence in high
      frequencies of alpha(+)-thalassemia in the coastal area of Madang and on the
      neighboring island, where malaria has long been holoendemic or hyperendemic, and
      its virtual absence from the nonmalarious highlands of PNG suggest the role of
      malaria as the selective factor in maintaining alpha(+)-thalassemia. If this
      selective pressure is still operating, and since alpha(+)-thalassemia has no
      apparent homozygous disadvantage, the abnormal haplotype (-alpha/) will be in the
      process of fixation in this population.

PMID- 9556667
TI  - The human salivary protein complex (SPC): a large block of related genes.
AB  - We have shown that genes for at least six human parotid proteins, parotid acidic
      protein (Pa), proline-rich protein (Pr), double-banded protein (Db), glycoprotein
      (Gl), parotid middle-band protein (Pm), and parotid-size variant (Ps) are linked.
      We have designated this complex of genes as the salivary protein complex (SPC).
      Several of the genes in this complex show marked associations that are most
      likely the result of linkage disequilibrium. It seems likely that the SPC arose
      through the process of gene duplication. This hypothesis is supported by the
      results of our present study that demonstrate the biochemical similarity of the
      protein products of several SPC genes. The amino acid compositions of the major
      SPC proteins are compared, including several (Ps 1 and 2, and Db) that have not
      been published. All of these proteins are quite similar and consist to a large
      extent of the amino acids, proline, glycine, and gix (glutamine and/or glutamic
      acid).

PMID- 9556668
TI  - Type IX Ehlers-Danlos syndrome and Menkes syndrome: the decrease in lysyl oxidase
      activity is associated with a corresponding deficiency in the enzyme protein.
AB  - Type IX of the Ehlers-Danlos syndrome (E-D IX) and the Menkes syndrome are X
      linked recessively inherited disorders characterized by abnormalities in copper
      metabolism. These abnormalities are associated with a severe reduction in the
      activity of lysyl oxidase, the extracellular copper enzyme that initiates
      crosslinking of collagens and elastin. No increase in this deficient enzyme
      activity was obtained when culture media from fibroblasts of patients with E-D IX
      or the Menkes syndrome were incubated with copper under various conditions in
      vitro. A distinct, although small, increase in lysyl oxidase activity was
      obtained, however, when copper-supplemented media were used during culturing of
      the fibroblasts, although even under these conditions, the enzyme activity in the
      media from the affected cells remained markedly below that of the controls.
      Immunoprecipitation, dot-blotting, and immunoperoxidase staining experiments with
      antisera to human lysyl oxidase indicated that fibroblasts from patients with E-D
      IX or the Menkes syndrome do not secrete into their medium, or contain inside the
      cell, any significant amounts of a copper-deficient, catalytically inactive lysyl
      oxidase protein. These findings appear to be consistent with the hypothesis that
      synthesis of the lysyl oxidase protein itself is impaired. The possibility is not
      excluded, however, that a copper-deficient enzyme protein may be synthesized in
      normal amounts but become degraded very rapidly inside the cell. The failure to
      obtain any large increase in the deficient lysyl oxidase activity upon various
      forms of copper administration suggests that it may not be possible to obtain any
      significant improvement in the connective tissue manifestations of these
      disorders by copper therapy.

PMID- 9556669
TI  - Basic fallacies in the formulation of the paternity index.
AB  - Some basic fallacies in the computation of the paternity index have been pointed
      out. The general finding that the true fathers' mean paternity index is greater
      than that of nonfathers is a necessary consequence of an algebraic identity,
      having nothing to do with paternity or nonpaternity. It has also been shown that
      the paternity index is not a likelihood ratio as claimed. The fact that a
      paternity index may frequently take values less than unity leads to absurd
      conclusions regarding the probability of paternity. A formula relating prior and
      posterior probabilities of paternity, based solely on genetic marker testing
      results (exclusion or nonexclusion), is reiterated as a substitute for the
      current paternity index.

PMID- 9556670
TI  - Guidelines for reporting estimates of probability of paternity.

PMID- 9556671
TI  - Chromosomal imprinting and the parent transmission specific variation in
      expressivity of Huntington disease.

PMID- 9556672
TI  - On citizenship in a great profession.

PMID- 9556673
TI  - Drug interaction triggers weakness.

PMID- 9556674
TI  - Understanding "sharp, shooting" pain.

PMID- 9556675
TI  - Gabapentin for lancinating neuropathic pain.

PMID- 9556676
TI  - The PSA test.

PMID- 9556677
TI  - The estrogen dilemma.

PMID- 9556678
TI  - Update on arrhythmias.

PMID- 9556679
TI  - Update on arrhythmias.

PMID- 9556680
TI  - Caring for adults with chronic cancer pain.

PMID- 9556681
TI  - Seven common legal pitfalls in nursing.

PMID- 9556682
TI  - Caring for Cody.

PMID- 9556683
TI  - Emergency! Malignant hyperthermia.

PMID- 9556684
TI  - Clinical snapshot: lung cancer.

PMID- 9556685
TI  - Basic assessment series. Gastrointestinal system.

PMID- 9556686
TI  - Women at high risk for breast cancer.

PMID- 9556687
TI  - Ensuring quality in continuing education.

PMID- 9556688
TI  - Thalidomide pros and cons.

PMID- 9556689
TI  - Rest in peace, Rabbi Shapiro.

PMID- 9556690
TI  - Asking patients about revising advance directives.

PMID- 9556691
TI  - Continuing education in an ever-changing career.

PMID- 9556692
TI  - [The path to "Doctor of Medicine"--how do doctoral candidates evaluate their
      dissertation?].
AB  - BACKGROUND AND OBJECTIVE: The value of medical dissertations has for some time
      been controversial. Critical opinions have, on the one hand, been directed
      against the effort required, its duration and the concept behind these
      dissertations, while asserting, on the other hand, that such dissertations hinder
      studying and lead to unnecessary lengthening of the medical curriculum.
      PARTICIPANTS AND METHOD: In collaboration with the Medical School in Hanover a
      questionnaire was sent to all the 189 dissertationists of one year, to be
      returned anonymously. It contained 16 questions about the dissertation itself,
      supervision. time spent on it, total duration of medical course and effect of the
      dissertation on the individual's medical studies. The answers were evaluated
      statistically by explorative data analysis. RESULTS: 181 questionnaires could be
      evaluated (96%). Average age of those questioned was 30.5 years, median duration
      of medical studies to-data was 13 semesters. For 80% it was the first attempted
      dissertation. 22% had been working on an entirely experimental topic (laboratory
      or animal experiments). The median time from starting to submitting the
      dissertation was 4 years, the median time of the experimental phase one year. Two
      thirds of students said that work on the dissertation had not prolonged their
      studies. Supervision during various phases of the dissertation was overwhelmingly
      judged to have been "very good" or "good". Altogether 90% of dissertationists
      thought that it had been personally meaningful, and they would recommend it to
      younger costudents. CONCLUSIONS: The results of this study show that a universal
      criticism of medical dissertations does not stand up to detailed enquiry.
      Successful dissertationists highly rated their value both to themselves and to
      scientific medicine. The medical dissertation should therefore firmly remain as
      part of medical studies and of research within them.

PMID- 9556693
TI  - [Strongyloides stercoralis infection in a patient with AIDS and non-Hodgkin
      lymphoma].
AB  - HISTORY AND CLINICAL FINDINGS: The patient, now 50 years old, an immigrant miner
      from the former Yugoslavia who was known to have AIDS, was in 1992 found to have
      non-Hodgkin lymphoma of the oesophagus and given five cycles of multiple
      chemotherapy (CHOP) with complete remission. Subsequently he complained of
      retrosternal pain, dysphagia, dry cough and upper abdominal discomfort. On
      admission he had slight fever of 39.1 degrees C, but physical examination was
      unremarkable. LABORATORY TESTS: Blood count revealed an eosinophilia of 41%. IgE
      concentration was raised to 432IU/ml. The CD4+ T-cell count was reduced to
      10/microliter, that of CD8+ to 89/microliter. ADDITIONAL TESTS: Blood culture,
      fecal and sputum samples and bronchoalveolar lavage demonstrated Mycobacterium
      avium intracellulare. TREATMENT AND COURSE: Treatment of the disseminated
      atypical mycobacterial infection was started with clarithromycin, rifabutin,
      ciprofloxacin and ethambutol. There was no improvement of the upper abdominal
      discomfort, but the fever subsided. Oesophagogastroscopy excluded recurrence of
      the lymphoma. Biopsy and examination of the duodenal juice revealed worms and
      larvae of Strongyloides stercoralis. Stool samples contained no mycobacteria, but
      strongyloides larvae were demonstrated. Albendazole was given (2 x 400 mg daily
      for 6 days, followed by a maintenance dose of 1 x 400 mg daily). Repeat endoscopy
      and stool sample after a month no longer showed any parasites. CONCLUSION: Even
      in Western Europe, persons coming from endemic areas who, as this patient, have
      various risk factors that may facilitate the occurrence of strongyloidiasis. With
      early diagnosis and treatment albendazole is an efficacious drug.

PMID- 9556694
TI  - [Suppurative acrodermatitis continua of Hallopeau. A differential diagnosis of
      paronychia].
AB  - HISTORY AND CLINICAL FINDINGS: A 39-year-old man was admitted for treatment of
      bilateral inflammatory-pustular skin changes in the area of the large toes and
      soles of the feet. Antibiotic treatment and an Emmert wedge resection had already
      been unsuccessfully performed at another hospital for what was diagnosed as
      paronychia. On admission there were inflammatory, in part erosive, red areas with
      yellow and partly confluent pustules on the distal phalanges of both great toes.
      The entire right nail-bed and left medial nail-bed were missing. In the area of
      the capillitium, both lower arms and the sulcus coronarius there were
      erythematous squamous plaques. INVESTIGATIONS: Radiography of the great toes
      demonstrated dystrophic demineralisation, in part with subchondral cystic changes
      of the spongiosa. Histological examination of the nail-bed showed hyperplasia and
      papillomatosis, definite hyperkeratosis with a prominent granular layer, as well
      as ortho- and parahyperkeratosis. Laboratory tests for inflammatory disease were
      unremarkable and there was no association with HLA B27. DIAGNOSIS, TREATMENT AND
      COURSE: Suppurative acrodermatitis continua of Hallopeau was diagnosed and
      immunosuppressive treatment with cyclosporin A given (initially 4.4 mg/kg.
      stepwise reduction to 2.5 mg/kg within 6 weeks, this dosage then continued for a
      further 10 weeks). Nearly complete healing was achieved, but the condition
      recurred in a mild form 2 weeks after the end of treatment. CONCLUSION:
      Suppurative acrodermatitis continua of Hallopeau should be included in the
      differential diagnosis of inflammatory changes of the distal phalanges.

PMID- 9556695
TI  - [Diagnosis of adrenal cortex diseases].

PMID- 9556696
TI  - [Hereditary hemochromatosis].

PMID- 9556697
TI  - [Gastroparesis--physiopathology, diagnosis and the latest therapy].

PMID- 9556699
TI  - [International comparison of clinical research in Germany].

PMID- 9556698
TI  - [Vaccination against early summer meningoencephalitis].

PMID- 9556700
TI  - D-lactic acidosis. A review of clinical presentation, biochemical features, and
      pathophysiologic mechanisms.
AB  - This report describes a case of d-lactic acidosis observed by the authors and
      then reviews all case reports of d-lactic acidosis in the literature in order to
      define its clinical and biochemical features and pathogenetic mechanisms. The
      report also reviews the literature on metabolism of d-lactic acid in humans. The
      clinical presentation of d-lactic acidosis is characterized by episodes of
      encephalopathy and metabolic acidosis. The diagnosis should be considered in a
      patient who presents with metabolic acidosis and high serum anion gap, normal
      lactate level, negative Acetest, short bowel syndrome or other forms of
      malabsorption, and characteristic neurologic findings. Development of the
      syndrome requires the following conditions 1) carbohydrate malabsorption with
      increased delivery of nutrients to the colon, 2) colonic bacterial flora of a
      type that produces d-lactic acid, 3) ingestion of large amounts of carbohydrate,
      4) diminished colonic motility, allowing time for nutrients in the colon to
      undergo bacterial fermentation, and 5) impaired d-lactate metabolism. In contrast
      to the initial assumption that d-lactic acid is not metabolized by humans,
      analysis of published data shows a substantial rate of metabolism of d-lactate by
      normal humans. Estimates based on these data suggest that impaired metabolism of
      d-lactate is almost a prerequisite for the development of the syndrome.

PMID- 9556701
TI  - Nosocomial colonization, septicemia, and Hickman/Broviac catheter-related
      infections in bone marrow transplant recipients. A 5-year prospective study.
AB  - In this 5-year prospective study of 242 bone marrow transplantation (BMT)
      recipients from whom daily blood cultures via the indwelling Broviac/Hickman
      catheter were obtained, there was a median of 35 catheter-days during
      hospitalization, mean of 40 days, and total of 9,667 catheter-days which were
      divided almost equally between neutropenic (4,771) and non-neutropenic (4,896)
      days. One hundred twenty (50%) patients had a total of 161 episodes of nosocomial
      bacterial or candidal infections. Overall, 81 (33%) patients experienced 100
      episodes of catheter-related infections and 90 (37%) patients experienced 112
      episodes of septicemia, including 51 episodes of catheter-related septicemia.
      There was an incidence of 11.59 septicemia episodes, including 5.28 catheter
      related septicemia episodes, 2.48 colonization only (without subsequent
      septicemia), and 2.59 exit site infections only, per 1,000 catheter-days. Over a
      period of a total of 6,593 afebrile days, 34 (14%) patients developed 40 episodes
      of colonization, a rate of 6.07 per 1,000 afebrile days, of which 16 developed
      into septicemia. Twenty-five patients had 1 episode each of exit site infection
      without bacteremia. There were 10 (4%) septicemia-related deaths, 4 of which were
      catheter-related; 50% of all deaths involved Pseudomonas aeruginosa. The
      mortality due to catheter-related septicemic episodes was not greater than that
      of the non-catheter-related episodes. Neutropenia was found to be a significant
      risk factor in our study: 76% of the septicemia episodes (85/112) and 65% of the
      catheter-related infectious episodes (65/100) occurred during neutropenia. There
      was a higher incidence of septicemic episodes during neutropenia than during non
      neutropenic periods, 17.82 versus 5.51 per 1,000 days (p < 0.0001), and a higher
      rate of catheter-related infections during the neutropenic period, 13.62 versus
      7.15 during non-neutropenic days per 1,000 days (0.001). Fourteen of 16
      colonization episodes developed into septicemia during neutropenia versus 2/24
      during non-neutropenic periods, a rate of 5.47 versus 0.47 per 1,000 afebrile
      days, respectively (p < 0.0001), and 9/10 deaths occurred during neutropenia.

PMID- 9556702
TI  - A review of epidemiologic studies of nonnarcotic analgesics and chronic renal
      disease.
AB  - The relationship of long-term and heavy exposure of nonnarcotic analgesics to the
      risk of chronic renal disease (CRD) has been the object of intensive clinical,
      pharmacologic, toxicologic, and epidemiologic research for 4 decades. The
      clinical evidence of an increased risk has been suggestive but inconclusive. The
      experimental evidence in animal models has been inconsistent, and in any case it
      cannot be generalized to humans. The epidemiologic evidence has been
      unsatisfactory for the most part: most of the early studies had severe
      methodologic limitations; moreover, they related mainly to phenacetin-containing
      drugs and did not have useful information on other analgesics. Since 1980, 9
      analytical epidemiologic studies have attempted to confirm that a causal
      relationship exists between phenacetin or other analgesics and CRD. In the
      aggregate, despite methodologic flaws, this work suggests that excessive use of
      phenacetin-containing analgesics probably causes renal papillary necrosis and
      interstitial nephritis. In contrast, there is no convincing epidemiologic
      evidence that nonphenacetin-containing analgesics (including acetaminophen,
      aspirin, and mixtures of these two compounds) or that nonsteroidal
      antiinflammatory drugs cause CRD. Moreover, the nature of dose-response
      relationships, the types of renal disease possibly caused by analgesics, and the
      cofactors that might be related both to analgesic use and to the development of
      CRD in humans are still uncertain, and the pathologic mechanisms of analgesic
      induced CRD in humans remain unclear. It may take many years before all the
      outstanding issues are settled. Until they are, as a matter of good clinical
      judgment it would be prudent to consider all analgesics as potentially
      nephrotoxic and, as much as possible, to avoid excessive, protracted use.

PMID- 9556703
TI  - Bacterial arthritis due to beta-hemolytic streptococci of serogroups A, B, C, F,
      and G. Analysis of 23 cases and a review of the literature.
AB  - The clinical features, essential laboratory findings, management, and outcome of
      all 23 cases of septic arthritis caused by different serogroups of beta-hemolytic
      streptococcus (BHS) seen at the Stanford Medical Center, Stanford, CA, from July
      1, 1985, through October 31, 1996, were reviewed and compared to those found in
      the literature. Group A streptococci (GAS) accounted for 9 (40%) of our cases;
      group B (GBS), for 7 (30%); and Group G (GGS), for 7 (30%). No cases were caused
      by Group C (GCS) or F (GFS) during this period. During the same period, GAS
      accounted for 66 (33%) of 200 cases of bacteremia due to BHS, GBS, for 98 (49%);
      GCS, for 12 (6%); GFS, for 4 (2%); and GGS, for 20 (10%). A review of potential
      risk factors revealed that, with the exception of GGS, male and female patients
      were almost equally distributed among each of the serogroups. Patients aged 50
      years and older comprised 56%-77% of each group. Associated conditions and risk
      factors were present among most patients (19/23, 83%); autoimmune diseases and a
      chronic skin wound or trauma were notably present among patients with GAS, while
      diabetes mellitus and malignancy were more common among patients with GBS.
      Infected prosthetic implants were present in 7 patients, including 4/7 patients
      with GGS. All patients had positive cultures of synovial fluid, and 11/23 (49%)
      had positive blood cultures (GAS, 5/9; GBS, 6/7; and GGS, 0/7). The clinical
      presentation and hospital course of patients infected with the different
      serogroups varied. Patients infected with GAS had the most severe disease and
      those with GGS the least severe. Necrotizing fascitis, shock, DIC, and admission
      to the intensive care unit were found only among patients infected with GAS.
      Despite aggressive management with antimicrobial therapy and surgery, 4/23
      patients died (3 patients with GAS; 1 with GBS). The isolates from our patients
      were not available for study; investigations by others of the biology of BHS
      suggest that the production of 1 or more of the streptococcal pyrogenic exotoxins
      by isolates of GAS may account for the differences in the severity of disease
      among our patients with septic arthritis caused by different serogroups of BHS.
      Although septic arthritis due to BHS is uncommon, such patients provide a
      valuable model to study features of the host-parasite interaction that may
      contribute to the observed differences in severity of disease.

PMID- 9556704
TI  - Prader-Willi and Angelman syndromes. Disorders of genomic imprinting.
AB  - Prader-Willi and Angelman syndromes are 2 clinically distinct disorders
      associated with multiple anomalies and mental retardation. They are only
      discussed together because they share a similar and uncommon genetic basis: they
      involve genes that are located in the same region in the genome and are
      characterized by genetic imprinting. This normal process has contributed to these
      2 complex and severe conditions through inactivation of 1 copy of the genes
      relevant to each disorder: the maternally derived copy of genes for Prader-Willi
      syndrome in proximal 15q are normally silent, and a paternally derived copy of 1
      gene for Angelman syndrome in 15q is normally silent. For both disorders, when
      the normally active copy of the gene or genes is missing, abnormality results.
      Since the genes for these 2 disorders are located very close together, and since
      the center involved in inactivating the genes involved in imprinting may be the
      same, both these disorders usually result from the same chromosomal deletion;
      which disorder results depends on the parent of origin of the chromosome 15 that
      becomes deleted. Both Prader-Willi and Angelman syndrome can also occur as a
      result of having both members of the chromosome 15 pair derived from 1 parent, a
      condition known as uniparental disomy. Both can also result from a structural
      abnormality of the imprinting center, known as an imprinting mutation. In
      addition, Angelman syndrome can be caused by a mutation in the gene that causes
      it; a comparable cause is not present in Prader-Willi syndrome since it results
      from abnormality in more than 1 gene. Finally, despite the complexity of possible
      causes, all but the single gene mutation of the Angelman syndrome gene can be
      detected through methylation-sensitive DNA probes, since DNA methylation is the
      process by which the genes for these 2 disorders are imprinted. This unusual
      property of specific areas of the DNA holds promise for future treatment of these
      and other disorders related to imprinting through reversal of the imprinting
      process.

PMID- 9556705
TI  - [Reconstructive procedures for restoring the hypopharynx after tumor excision].

PMID- 9556706
TI  - [Effect of benzalkonium chloride on ciliary epithelium of the mucosa].

PMID- 9556707
TI  - [Reflections on simultaneous radio-polychemotherapy in head-neck carcinomas].

PMID- 9556708
TI  - [Comments on the contribution by U. Goede. Maxillary sinus fenestration via the
      middle vs. lower nasal passage].

PMID- 9556709
TI  - [Aphthae and aphthous lesions of the mouth mucosa].
AB  - Recurrent aphthae (or aphthoses) are the most frequent inflammatory lesions of
      the oral mucosa. Aphthae can clearly be defined, but may also be barely
      discernible from aphthoid erosions and ulcers of heterogeneous origin. Although a
      subject of molecular research, the etiopathogenesis of oral aphthoses is still
      unknown. However, the clinical differentiation of a "benign" type of aphthosis
      from a "pernicious" one, such as Behcet's disease (BD), is a diagnostic matter of
      great significance. BD has been found clinically in increasing numbers in central
      Europe and represents an (auto-)hyperimmune multisystem life-threatening
      vasculitis. In this disorder possible damage can occur to many visceral organs
      and/or the cerebrospinal system. The prognosis of BD may depend on the changing
      involvement of very different organs, as well as the early recognition of the
      disease per se. The most prominent feature is a multilesional aphthous stomatitis
      that is almost never absent during acute episodes of BD. Hence, the occurrence of
      this peculiar type of aphthosis strongly indicates an active BD. The plethora of
      other aphthoid lesions can be challenging to the diagnostic competence of all
      physicians and may confuse the correct recognition of the severity of the disease
      present. This review particularly details the wide range of diagnostic,
      therapeutic and prognostic aspects of the various oral aphthoses.

PMID- 9556711
TI  - [Finite element modeling and simulation of the human tympanic membrane].
AB  - Besides a knowledge of material properties geometric properties are needed to
      investigate the mechanical behavior of the human eardrum. Although the geometry
      of the eardrum has been examined methodically, its composition has been described
      in the literature. The true surface geometry of a cadaver specimen of the human
      eardrum was examined under a laser-scanning microscope. Forty points (85
      parameters) depicted the surface of this cadaver specimen and formed the basis
      for a finite shell model. Furthermore, the coupling with the malleus and its
      suspension was simulated. Additional geometric and material parameters were
      chosen from the available literature. Both static behavior and the influence of a
      parameter variation to modal behavior of the finite element model were tested.
      ANSYS 5.1 software was used for this study.

PMID- 9556710
TI  - [Principles of energy sources of totally implantable hearing aids for inner ear
      hearing loss].
AB  - A fully implantable hearing aid consists of a sound receptor (microphone), an
      electronic amplifier including active audio-signal processing, an
      electromechanical transducer (actuator) for stimulating the ear by vibration, and
      an energy source. The energy source may be either a primary cell or a
      rechargeable (secondary) cell. As the energy requirements of an implantable
      hearing aid are dependent on the operating principle of the actuator, the
      operating principles of electromagnetic and piezoelectric transducers were
      examined with respect to their relative power consumption. The analysis showed
      that the energy requirements of an implantable hearing aid are significantly
      increased when an electromagnetic transducer is used. The power consumption of a
      piezoelectric transducer was found to be less than that of the electronic
      components alone. The energy needed to run a fully implantable hearing aid under
      these conditions would be 38 mWH per day. Primary cells cannot provide the energy
      needed for a minimum operation time of 5 years (70 WH), and therefore
      rechargeable cells must be used. A theoretical appraisal was carried out on
      nickel-cadmium, nickel-metal hydride, and lithium-ion cells to determine their
      suitability as well as to assess the risks associated with their use in an
      implant. Safety measures were drawn up from the results. Ni-MH cells were found
      to be the most suitable for use as an energy source for implantable hearing-aids
      because they are more robust than Li ion cells and their storage capacity is
      double that of Ni-Cd cells of similar size.

PMID- 9556712
TI  - [Larynx preserving surgery in carcinomas of the posterior hypopharyngeal wall by
      reconstruction with a free flap].
AB  - In a series of 9 patients with advanced carcinomas of the posterior wall of the
      hypopharynx (2 patients with T2 tumors and 7 patients with T4 disease), we tried
      to preserve the larynx with surgical therapy. The concept of laryngeal
      preservation consisted of lateral pharyngotomy with free flap reconstruction of
      the defect created by the tumor resection. A recommendation for surgery was given
      to each patient with a neoplasm in the posterior pharyngeal wall and tumor
      extension > 6 cm in diameter. The maximum tumor diameters ranged between 6.5 cm
      and 12.5 cm. Reconstruction was performed in 8 cases with radial forearm flaps
      while a jejunal transplant was used in one case due to the extension of tumor.
      During each surgical procedure an attempt was made to preserve the superior
      laryngeal nerves and transplants were adapted exactly to the resection defects.
      Seven patients achieved oral swallowing within three months of surgery, while one
      patient needed four months to swallow orally. One patient had persistent
      aspiration and still needs a percutaneous gastrostomy. Six patients were
      decannulated successfully, so that laryngectomy was avoided during postoperative
      follow-up. These results show that surgical therapy of advanced carcinoma of the
      posterior wall of the hypopharynx is possible with preservation of the larynx.
      Additionally, functional outcome after treatment of these patients with free flap
      reconstruction is comparable to other treatment modalities, such as
      radiochemotherapy.

PMID- 9556713
TI  - [Hyperfractionated accelerated simultaneous radiochemotherapy in advanced
      hypopharyngeal carcinomas. Survival rate, retained function quality of life in a
      phase II study].
AB  - Forty-one patients with locally advanced hypopharyngeal carcinomas were followed
      for at least 3 years (median, 60 months) after simultaneous radiochemotherapy.
      Conventionally fractionated radiotherapy was administered as 5 x 2 Gy/week to a
      total dose of 30 Gy within 3 weeks. From the fourth week an accelerated
      hyperfractionated schedule was used as 2 x 1.4 Gy/day five days weekly given
      exclusively to the first order target volume of macroscopic tumor (adding up to a
      total dose of 72 Gy in six weeks). The second and third order target volumes
      received conventional fractionation only to 60 Gy and 50 Gy, respectively. The
      moderate acceleration of the concomitant boost scheme in the second half was
      counterbalanced during the first week by the introduction of a 5-fluorouracil
      bolus of 350 mg/M2 with 200 mg/M2 folinic acid and a subsequent continuous
      infusion using the same dose each 24 h for 5 days. Additionally, a Mitomycin-C
      bolus of 10 mg/M2 was infused at the fifth day and on the first day of the sixth
      week. Six weeks after treatment the patients were restaged. In cases with
      residual carcinoma salvage surgery was performed (11 patients). Late effects of
      therapy were analyzed according to the Lent-Soma index and life quality according
      to the European Organisation for Research and Treatment of Cancer-Module. Late
      effects of treatment were tolerable and were controlled locally. The 3-year
      survival rate was 39%, with a local-regional recurrence-free control rate of 71%.
      Fifty-two percent of all cases of death were caused by distant metastases,
      secondary carcinomas or other diseases not related to tumor recurrence. The poor
      prognosis of hypopharyngeal carcinomas despite acceptable local tumor control may
      be due to specific biological factors present in affected patients.

PMID- 9556714
TI  - [Effect of topical corticosteroids and topical antihistaminics on ciliary
      epithelium of human nasal mucosa in vitro].
AB  - A normal ciliary beat frequency of ciliated cells is necessary for the
      mucociliary clearance of the nose and paranasal sinuses. An in vitro
      investigation was performed to evaluate the influence of topical corticosteroids
      and antihistamines on the ciliary beat frequency of human nasal mucosa. The nasal
      sprays examined contained the corticosteroids budesonide or fluticasone
      propionate and the topical antihistamines azelastine or levocabastine. All tests
      were performed on cell cultures of human nasal mucosa during constant conditions.
      Three of the four nasal sprays tested contained benzalkonium chloride as
      preservative. An irreversible cessation of ciliary movement was observed in all
      cells exposed to nasal sprays containing benzalkonium chloride in a 50 per cent
      solution. The nasal spray containing budesonide was benzalkonium chloride-free
      and caused minor but fully reversible decreases in ciliary beat frequency after
      20 min. As benzalkonium chloride can cause complete standstill of ciliary beat
      frequency in vitro in human nasal mucosa, we recommend that this preservative
      should not be used anymore in topical nasal medications.

PMID- 9556715
TI  - [Early trans-sphenoid decompression in indirect traumatic optic neuropathy].
AB  - BACKGROUND: Indirect traumatic optic neuropathy represents a severe, potential
      vision-threatening disease process that requires close interdisciplinary
      cooperation for treatment. In general, any therapy has been discussed
      controversially in the literature. Based upon experiences with spinal cord
      trauma, high-dose steroid therapy is recommended initially to minimize secondary
      consequences following orbital trauma. The usefulness of surgical decompression
      of the optic nerve has been confirmed in several studies but is still not
      recommended in principle. PATIENTS AND METHOD: In nine consecutive patients with
      known indirect traumatic optic neuropathy and marked losses of vision,
      transsphenoidal optic decompressions were carried out with simultaneous systemic
      megadose steroid therapy. RESULTS: A postoperative increase in visual acuity from
      1/35 to 10/20 occurred in five patients, while no improvement in visual acuity
      could be achieved in the other four patients. DISCUSSION AND CONCLUSION: Previous
      reports have indicated that some authors will not recommend surgical
      decompressions if a loss of sight or no light perception occurs directly after an
      accident. This situation was seen in seven of our patients. The visual acuity of
      four patients remained no light perception in spite of surgical treatment. In
      three other patients, an increase in visual acuity from amaurosis improved to
      1/35, 4/20 and 8/20, respectively, following early decompression combined with
      steroids. This experience together with the positive results of other studies
      supports carrying out decompressions of the optic nerve, even when an amaurosis
      occurs directly after trauma.

PMID- 9556716
TI  - [Strategies in ambulatory treatment of tinnitus].

PMID- 9556717
TI  - [Sudden deafness. Dissection of the internal carotid artery].

PMID- 9556718
TI  - [Endoscopic resection of juvenile nasopharyngeal fibromas].
AB  - Current surgical approaches to juvenile nasopharyngeal angiofibromas (JNA) are
      exclusively external. This implies not only incisions that are mostly visible,
      but also a potential loss of function as well as secondary lesions and high
      perioperative risks. Radiotherapy aims to avoid surgery, but cannot exclude
      complications and possible sequelae. These consequences are commonly accepted as
      the "costs" for both therapies, although neither is negligible. For both surgery
      and radiotherapy, recurrences or persistence rates have been described, so that
      outcome may result in questions for the treatment used as well as the
      complications or sequelae. We report our experiences with two cases of JNA
      operated on under endoscopic control and discuss our indications for the
      endoscopic approach to these tumors, preoperative conditions, surgical technique,
      and the possible difficulties of surgery and outcome. Our results encourage us to
      recommend use of endoscopic surgery as a valid alternative method to approach
      resections of certain JNA.

PMID- 9556719
TI  - [Metastatic spread of renal cell carcinoma in the area of the ethmoid and frontal
      sinuses].
AB  - Metastatic lesions represent 1-8% of all malignant tumors of the mouth and jaws,
      with rare sites of metastasis originating from different primary tumors,
      especially the lung and breast. The vast majority of these lesions (up to 90%)
      have been observed in the mandible and maxilla (5-20%). Another rare type of
      cancer that usually metastasizes to the lungs, lymph nodes, bones, liver or brain
      may occasionally also show spread to the paranasal sinuses. In the present paper
      we report our management of a 50-year-old male with renal cell carcinoma who
      developed metastases to the frontal and ethmoid sinuses.

PMID- 9556720
TI  - [Sensitization to chlorhexidine].

PMID- 9556722
TI  - [Guidelines in ENT. How essential are they?].

PMID- 9556721
TI  - [Wound infection caused by iron].

PMID- 9556723
TI  - [Subjective and objective methods for evaluating sense of smell].

PMID- 9556724
TI  - [Urgent care physician and emergency physician. Responsibilities of emergency
      medicine].

PMID- 9556725
TI  - [Quality assurance in emergency medicine].

PMID- 9556726
TI  - [The acute coronary syndrome].

PMID- 9556727
TI  - [Recommendations for preclinical emergency medicine. Acute therapy of tachycardic
      cardiac arrhythmias].

PMID- 9556728
TI  - [Acute dyspnea].

PMID- 9556729
TI  - [Preclinical emergency medicine. Acute abdomen].

PMID- 9556730
TI  - [Hypersensitivity reactions].

PMID- 9556731
TI  - [Cardiopulmonary resuscitation. Presentation and commentary on current
      guidelines].

PMID- 9556732
TI  - [Polytrauma].

PMID- 9556733
TI  - [Anuria].

PMID- 9556734
TI  - [50-year-old patient with left-sided inguinal pain].

PMID- 9556735
TI  - [51-year-old patient with reversible infarct-like ECG changes].

PMID- 9556736
TI  - [Homocysteine and atherogenesis].

PMID- 9556737
TI  - [When use thrombolysis?].

PMID- 9556738
TI  - [Determination of coronary flow reserve].

PMID- 9556739
TI  - [Procedure for intracardiac thrombosis].

PMID- 9556740
TI  - [Acetylsalicylic acid and surgical risk].

PMID- 9556741
TI  - [Indications for acetazolamide in neurology].

PMID- 9556742
TI  - [Metformin in diabetes therapy].

PMID- 9556743
TI  - Improved nuclear magnetic resonance microscopic visualization of joint cartilage
      using liposome entrapped contrast agents.
AB  - RATIONALE AND OBJECTIVES: After intraarticular application of gadolinium (Gd)
      DTPA the visualization cartilage surface roughness is limited because of
      diffusion into the cartilage. To improve the sensitivity of magnetic resonance
      (MR) arthrography to diagnose cartilage surface abnormalities, the authors have
      tested liposome-entrapped contrast agents. METHODS: Using paramagnetic contrast
      agents (Gd-DTPA and manganese chloride) free and entrapped in liposomes,
      respectively, high resolution MR imaging investigations were performed at 7.1
      tesla on intact pig temporomandibular and rabbit knee joints. RESULTS: After
      intraarticular injection of the liposome-entrapped contrast agents an excellent
      contrast between cartilage surface and joint space was achieved. Diffusion of the
      contrast agent into the cartilage layer was prevented and the visualization of
      the cartilage surface was improved markedly. Small mechanically and enzymatically
      induced cartilage lesions could be assessed reliably. CONCLUSIONS: Intraarticular
      injection of liposome-entrapped contrast agents can improve the potential of MR
      arthrography concerning the detection of early osteoarthritic cartilage changes.

PMID- 9556744
TI  - Why do anatomic backgrounds reduce lesion detectability?
AB  - RATIONALE AND OBJECTIVES: Developing metrics of medical image quality requires an
      understanding of how anatomic backgrounds reduce human visual detection
      performance. Visual psychophysics has shown that there are two distinct ways in
      which a complex background can degrade performance: (1) the presence of a
      deterministic high-contrast background, (2) variability in the background from
      location to location. The authors investigated how these two sources of
      performance degradation reduce human visual performance locating a lesion in
      anatomic backgrounds. METHODS: Human performance localizing a disk-shaped lesion
      in one of four locations (four alternative forced choice) was measured for three
      background conditions. In the first condition the background was a uniform gray.
      In the second condition (the repeated background condition) an anatomic
      background was sampled on each trial and used as a background for the four
      possible lesion locations. In the third condition (the different background
      condition) four different anatomic backgrounds were sampled on each trial and
      used for the four possible lesion locations. Test images consisted of computer
      simulated lesions mathematically projected on digital x-ray coronary angiograms.
      RESULTS: For five levels of lesion contrast, visual detection performance for two
      observers decreased significantly from the uniform background condition to the
      repeated background condition, and decreased even further for the different
      background condition. CONCLUSIONS: Study results show that both the presence of a
      deterministic high-contrast background and the background variations contribute
      to performance degradation of human visual detection of signals in anatomic
      backgrounds.

PMID- 9556745
TI  - Assessment of myocardial perfusion by intermittent harmonic power Doppler using
      SonoVue, a new ultrasound contrast agent.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the potential of SonoVue, a new
      echo contrast agent, for the detection of myocardial perfusion abnormalities
      using intermittent harmonic power Doppler (IHPD) imaging and different pulse
      repetition frequencies (PRFs). METHODS: Experiments were performed in vitro (in a
      tissue-mimicking phantom) and in vivo (in minipigs) in harmonic power Doppler
      using an ATL HDI 3000 with second harmonic software. SonoVue was injected
      intravenously in an auricular vein in bolus (dose range 0.01-0.05 mL/kg) in
      closed-chest animals or as an infusion (rate = 0.1 mL/kg/minute) in open-chest
      minipigs with reversible left anterior descending coronary artery (LAD)
      occlusion. The animals were imaged using IHPD gated on the electrocardiogram at
      end-systole (pulsing interval at each cardiac cycle). The efficacy of SonoVue was
      evaluated at six PRFs from 500 to 6000 Hz either qualitatively using a subjective
      scoring system or quantitatively using a digital image analyzer. RESULTS: SonoVue
      at a dose of 0.01 mL/kg produced a strong and homogeneous myocardial
      opacification in IHPD. Higher doses prolonged the duration of the contrast
      effect. Varying the PRF allowed the discrimination of flow velocities in vitro
      and the detection of perfusion differences within the myocardium during transient
      LAD occlusion and during immediate reperfusion in vivo. Low PRFs were
      particularly useful to differentiate the ischemic bed from the healthy one during
      LAD occlusion. The high flows caused by coronary hyperemia during immediate
      reperfusion were detected clearly in the reperfused area at high PRFs.
      CONCLUSIONS: SonoVue is a promising agent for myocardial opacification studies
      using IHPD. The latter imaging modality is particularly well suited for blood
      flow detection in tissues. Varying the PRF provides additional information on
      flow velocity and improves the detection of perfusion differences in the
      myocardium.

PMID- 9556746
TI  - Biphasic spiral computed tomography for detection of hepatocellular carcinoma
      before resection or orthotopic liver transplantation.
AB  - RATIONALE AND OBJECTIVES: The authors correlate computed tomography (CT) findings
      in biphasic spiral technique with histopathology in patients with hepatocellular
      carcinoma (HCC) who had undergone liver resection (LR) or orthotopic liver
      transplantation (OLT). METHODS: Preoperative biphasic spiral CT findings in 33
      consecutive patients (23 men, 10 women, aged 43-74 years; LR group: n = 17; OLT
      group; n = 16) with liver cirrhosis and HCC were reviewed retrospectively by
      consensus of two radiologists and correlated with pathology from liver specimens.
      RESULTS: Of the 16 patients in the OLT group with 1 to 5 confirmed HCC lesions
      (total lesions: 29; mean lesion diameter: 2 cm; range: 0.6-5.0 cm), CT before OLT
      depicted 22 lesions in 15 patients (sensitivity for lesions with a diameter of
      0.5-1.0 cm, 20%; for lesions 1.1-2.0 cm, 82%; and for lesions 2.1-3.0 cm and >
      3.0 cm, 86% and 100%, respectively). Among the 17 patients in the LR group (total
      lesions: 21; mean lesion diameter: 5.4 cm; range: 1.0-11.0 cm), CT detected 18
      lesions. Lesion-by-lesion sensitivity, as correlated with pathology, was
      calculated at 76% and 86% in the OLT and LR groups, respectively (overall
      sensitivity, 80%). The diameter of CT detected lesions, compared with liver
      specimens, corresponded in 90% of lesions (maximum deviation, 15%).
      Characteristic CT findings of HCC included unenhanced hypoattenuating focal liver
      lesions (32 lesions), with hyperattenuation (38 lesions) in the arterial phase of
      contrast material administration. CONCLUSIONS: Biphasic spiral CT for
      preoperative HCC detection correlated with pathology in 80%, thus proving this
      technique to represent a sensitive imaging modality for pretherapeutic evaluation
      of HCC.

PMID- 9556747
TI  - Magnetic resonance features of the enigmatic oligodendroglioma.
AB  - RATIONALE AND OBJECTIVES: The authors characterize magnetic resonance (MR)
      features of oligodendroglioma that permit diagnosis. These features may be used
      to guide MR stereotactic biopsies. METHODS: Fifteen patients with mixed
      oligodendroglioma and four with pure oligodendroglioma were studied on a 1.5
      tesla MR unit with contrast and also by computed tomography (CT). All patients
      had their diagnosis confirmed by light and electron microscopy, and by
      immunohistochemical staining. RESULTS: The most characteristic finding was a
      honeycomb tumor matrix (4 of 19) in oligodendroglioma. The most common finding
      was an amorphous pattern (12 of 19) and the least common was a large cystic
      pattern (3 of 19). Contrast enhancement most commonly was minimal and dot-like or
      lacy in appearance (11 of 19), or absent (5 of 19). Calcification was present in
      the majority (11 of 19). CONCLUSIONS: The honeycomb and stippled amorphous
      patterns reflect the cytoarchitecture of oligodendroglioma and were the most
      characteristic MR features. The amorphous pattern was the most commonly
      encountered pattern. There was a wider range of imaging findings on MR compared
      with CT; the flocculent calcification on CT was typical, but it was not always
      detected on MR. Including these characteristic areas that appear along the path
      of the stereotactic biopsy may ensure a correct diagnosis of oligodendroglioma
      because it most often is seen with another tumor, usually of the astrocytic
      family. Identifying the oligodendrogliomatous portion of the tumor will influence
      the therapy. No differences could be found in the MR appearance or biologic
      behavior of pure versus mixed oligodendrogliomas.

PMID- 9556748
TI  - Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis. Evaluation
      of 250 patients.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the sensitivity and specificity of
      a bedside test (SimpliRED) in the diagnosis of deep vein thrombosis compared with
      contrast phlebography. METHODS: Two hundred fifty patients, referred for
      phlebography, underwent bedside testing for detection of deep vein thrombosis.
      Contrast phlebography was performed immediately afterward. SimpliRED provides a
      clearly visible agglutination of the patient's red blood cells in the presence of
      elevated levels of cross-linked fibrin derivative (D-dimer), which is specific
      for fibrin breakdown. RESULTS: In 82 (32.8%) patients, deep vein thrombosis was
      confirmed venographically. An abnormal D-Dimer test was found in 79 of the 82
      patients with thrombosis (sensitivity: 96.3%). The three patients who were
      diagnosed falsely as normal on agglutinin testing, had venograms which showed
      only an isolated calf thrombosis in small muscle veins (< 2 cm in diameter) not
      requiring treatment. One hundred of 168 patients without venographic thrombosis
      were diagnosed correctly by SimpliRED (specificity: 59.5%). The positive
      predictive value was 53.7%; the negative predictive value was 96.8%. CONCLUSIONS:
      All thrombotic disorders in the leg that required further treatment were
      identified correctly. SimpliRED is a very sensitive test with moderate
      specificity in the diagnosis of deep vein thrombosis. Therefore, further invasive
      testing is needed only in those patients in whom the D-dimer test is abnormal. A
      false-positive result of the bedside test may be nonspecific or due to elevated
      levels of fibrin split products, which can occur whenever the coagulation system
      has been activated by any of several conditions.

PMID- 9556749
TI  - Mechanisms of accumulation of small particles of iron oxide in experimentally
      induced osteosarcomas of rats: a correlation of magnetic resonance imaging and
      histology. Preliminary results.
AB  - RATIONALE AND OBJECTIVES: This study was conducted to investigate the
      distribution and kinetics of small particles of iron oxide in osteosarcoma-like
      tumors. METHODS: Magnetic resonance (MR) imaging was performed in eight athymic
      nude rats with an experimentally induced osteosarcoma of the right hind leg
      immediately after intravenous injection of a superparamagnetic iron oxide
      preparation. Five animals received 150 mumol iron oxide/ kg and three received 50
      mumol iron oxide/kg. The iron oxide preparation consisted of polythylenglycol
      coated particles with a core diameter of 6 to 8 nm. The MR images were correlated
      with histologic slices of the tumors. RESULTS: The tumors accumulated iron oxide
      rapidly. A marked decrease in signal intensity, preferentially along the
      periphery of the tumor, was followed by a partial return of the signal intensity
      within the first minute. The maximum signal decrement throughout the entire tumor
      exceeded 41% and 21% with one dose each of 150 mumol iron/kg and 50 mumol
      iron/kg, respectively. The rate of return depended on the injected dose and tumor
      area, with the signal intensity approaching the initial value before the
      injection of iron oxide after 45 minutes. Histologic correlation only showed
      deposition of contrast medium in the proliferative areas of the tumors, mainly
      confined to the tumor margin. In addition to a predominantly extracellular
      deposition, intracellular storage could be detected. CONCLUSIONS: The findings
      help to advance the understanding of the distribution and kinetics of intravenous
      injected small particles of iron oxide in osteosarcoma-like tumors. A first-pass
      accumulation of iron oxide could be documented by MR imaging in the periphery of
      osteosarcomas. Due to sieving of iron oxide particles by liver, spleen, and bone
      marrow, the signal intensity at 45 minutes after the injection of iron oxide
      returned to 89% (150 mumol iron oxide/kg) and 95% (50 mumol iron oxide/kg) of the
      preinjection intensity.

PMID- 9556750
TI  - Magnetic resonance imaging in a spinal abscess model. Preliminary report.
AB  - RATIONAL AND OBJECTIVES: Magnetic resonance (MR) scan technique and lesion
      detectability were evaluated using a newly developed spinal abscess model in the
      New Zealand White rabbit. METHODS: To create the lesion, an epidural needle was
      inserted under fluoroscopic guidance in the lumbar region and advanced to
      penetrate the ligamentum flavum. Next, polyethylene tubing was fed through the
      needle into the epidural space. A mixed suspension of Staphylococcus aureus
      (Cowan I) and blue polystyrene microspheres then was injected. Lesions were
      evaluated by MR imaging in four animals at multiple time points (3, 6, and 9
      days). Imaging was performed at 1.5 tesla using a surface coil. Precontrast T2
      and T1-weighted scans were first obtained. The T1-weighted scans were acquired
      both with and without fat saturation, and were repeated after intravenous
      contrast administration. The contrast agent used was gadoteridol (gadolinium HP
      DO3A or ProHance) at a dose of 0.3 mmol/kg. RESULTS: On prospective film review,
      postcontrast scans proved superior for lesion detection. A spinal abscess could
      be identified postcontrast in all cases, irrespective of the use of fat
      saturation. The next best imaging technique for lesion detection was the T2
      weighted scan, with 5 of 8 lesions noted thereon. Visualization of lesion margins
      proved to be a primary factor in prospective lesion identification. Region of
      interest image analysis demonstrated the postcontrast scans to be superior to all
      precontrast scan techniques for conspicuity of the interface between the abscess
      and the compressed spinal cord, with these results statistically significant. The
      lesions were characterized histologically by infiltrates of heterophils into the
      meninges and outer spinal cord with accompanying mild hemorrhage, fibrin
      exudation, and bacterial colonies. The lesions in three animals were confirmed to
      be in the epidural space, with the lesion in one animal in the subdural space.
      CONCLUSIONS: The current animal model was developed to study spine infection and,
      specifically, imaging characteristics and lesion detectability on MR. With the
      increased use of epidural catheters for pain management and the large number of
      acquired immunodeficiency syndrome cases, epidural infection is becoming an
      increasingly important clinical problem. Imaging technique, in particular the use
      of intravenous contrast, is critical for lesion detection and evaluation.

PMID- 9556751
TI  - Entomological and rodent surveillance in plague-suspected areas during September
      1994 and thereafter.
AB  - Studies carried out in the states of Maharashtra, Gujarat, Uttar Pradesh and
      Union Territory of Delhi after the bubonic plague outbreak during 1994 revealed
      the presence of seven species of rodents, viz. Rattus rattus, R. norvegicus, Mus.
      musculus, Tatera indica, Suncus murinus, Bandicoota bengalensis and B. indica.
      The flea species encountered were Xenopsylla cheopis and X. astia. The X. cheopis
      and X. astia index recorded in different areas of Beed district of Maharashtra;
      Surat, Vadodra and Baruch districts in Gujarat and Varanasi district in Uttar
      Pradesh and their implications have been discussed. Insecticide suspectibility
      tests carried out against DDT, dieldrin, malathion and deltamethrin with X.
      cheopis collected from Maharashtra, Delhi and Varanasi revealed that this vector
      species is resistant to DDT and dieldrin but susceptible to malathion and
      deltamethrin. The prevalence and distribution of rodents species, high cheopis
      index and prevalence of Tatera indica just at the door steps of houses in village
      Mamla of Beed district provides highly congenital conditions for the
      intermingling of wild and domestic rodents and transfer of flea population from
      wild to domestic rodents and vice-versa. These conditions were found to be highly
      supportive for bubonic plague transmission in the district. The presence of
      Yersinia pestis antibodies in Rattus rattus collected from Beed, Surat and
      Varanasi areas are also indicative of bubonic plague in Beed and Varanasi and
      pneumonic plague in Surat during 1994.

PMID- 9556752
TI  - Molecular typing of Vibrio vulnificus isolates by random amplified polymorphic
      DNA (RAPD) analysis.
AB  - This study was undertaken to determine molecular types and genetic similarity
      among V. vulnificus isolates by RAPD analysis. We compared these results with
      serotypes of V. vulnificus. Ninety-seven V. vulnificus strains including 69
      strains from Chonnam University Hospital (CUH; Kwangju, Korea), 13 from Wonkwang
      University Hospital (WUH; Iksan, Korea), 13 from the Japanese National Institute
      of Health (JNIH) and two reference strains (ATCC 33815 and ATCC 27562) were
      analyzed. Four molecular types comprising all the strains were obtained by RAPD
      analysis. Type I was the most common (60/95) and included 58 strains from CUH.
      Type I showed a further subdivision into seven subtypes. Type II (23/95) composed
      of 11 strains from CUH, nine from WUH, three from JNIH and two reference strains.
      Six type III strains comprised four WUH strains and two JNIH strains. All six
      strains of type IV were from JNIH. The range of genetic similarity values among
      V. vulnificus isolates was 0.24 to 1.00. The serotypes of 95 strains were 04
      (84.2%), 014 (3.2%), 01 (2.1%), 013 (2.1%), and R (2.1%). The most common 04
      serotype strains were distributed among types I (60 strains), II (23 strains),
      III and IV (six strains). Although the V. vulnificus isolates showed a wide range
      of genetic similarity values, RAPD analysis could separate V. vulnificus strains
      into four molecular types, and the isolates from the same hospitals tended to
      belong to the same molecular type. There was no specific correlation between
      molecular types and serotypes of V. vulnificus.

PMID- 9556753
TI  - The latest seroepidemiological pattern of hepatitis A in Japan.
AB  - Age-specific prevalence of anti-hepatitis A virus antibody (anti-HAV) was
      surveyed with 2,708 sera collected in 1994 in various areas of Japan. By age
      group analyses, we found strong association of anti-HAV antibody with higher age
      group. The prevalence ratios of antibody in the groups of 30-34, 35-39, 40-44, 45
      49, 50-54, 55-59, 60-64 and 65 years or older were 0, 4.2, 22.0, 44.8, 57.6,
      76.4, 84.5 and 91.4%, respectively. Geometric mean titers of anti-HAV antibody in
      the positive age groups were approximately 6,000 mIU/ml. The seropositives among
      older population were ascribed to the infections more than 40 years ago and the
      high anti-HAV titers have been maintained since that time. In Japan, people
      younger than 40 years of age are extremely risky to HAV infection, since 99% have
      no antibody. Those in forties are also risky since two-thirds of them are
      seronegative. In Japan, an inactivated vaccine was licensed in 1994. Vaccination
      may be recommended for such high-risk groups as travelers going to endemic areas,
      patients who have received blood product medication and child-care staffs.

PMID- 9556754
TI  - Rapid and highly sensitive enzyme immunoassay for quantitative determination of
      tetrodotoxin.
AB  - A monoclonal antibody against tetrodotoxin (TTX) was obtained from Balb/c mice
      immunized with TTX-bovine serum albumin (BSA) conjugate. The monoclonal antibody
      was highly specific for TTX and had no cross-reaction to tetrodonic acid, which
      is a TTX derivative, or gonyautoxins, although a minor cross-reaction to anhydro
      tetrodotoxin was observed. The monoclonal antibody neutralized the lethal
      activity of TTX. By using the monoclonal antibody, a rapid and highly sensitive
      competitive enzyme immunoassay (EIA) for quantitative analysis of TTX was
      developed. By the competitive EIA system, TTX can be determined quantitatively in
      about 30 min (90 min are required if the time for preparation of the solid-phase
      antigen was included), and the working range for quantitative analysis of TTX was
      2-100 ng/ml. In recovery tests and examinations of TTX samples, results of the
      mouse bioassay and EIA analyses correlated well (r = 0.987). Moreover, it was
      demonstrated that low concentrations of TTX, which could not be detected by the
      mouse bioassay, could be determined quantitatively by the competitive EIA.

PMID- 9556755
TI  - Screening of human corneas for herpes simplex virus by tissue culture and
      polymerase chain reaction.
AB  - Superficial eye infections by herpes simplex virus (HSV) constitute a major cause
      of corneal disease, necessitating the need for corneal transplantation in many
      patients. Eighty-three corneas from 46 post-mortem donors received from the David
      Lucas Eye Bank in Manchester were analyzed by Vero cell culture and the
      polymerase chain reaction (PCR) technique to detect HSV. There was no evidence of
      a characteristic cytopathic effect in any of the cultures. A 350-bp PCR product
      corresponding to the HSV thymidine kinase (TK) was detected by southern blotting
      in only 2.4% (2/83) of samples. In contrast, approximately 70% of samples yielded
      a 758-bp PCR product. Although this low prevalence of HSV in corneas may be
      encouraging, it is high for the actual transplantation program if the viral DNAs
      maintain their abilities to replicate.

PMID- 9556756
TI  - Detection of HeLa cell contamination--presence of human papillomavirus 18 DNA as
      HeLa marker in JTC-3, OG and OE cell lines.
AB  - There are warnings of the contamination of cell cultures with HeLa cells in many
      laboratories in the world. The cell lines JTC-3, OG and OE that were established
      in Okayama in 1959, 1969 and 1971, respectively, were examined for human
      papillomavirus (HPV) 18 DNA by Southern blot hybridization. The HPV 18 DNA
      detected in these three cell lines showed hybridization patterns characteristic
      of the HPV 18 DNA in the HeLa cell line established in 1951. Southern
      hybridization patterns of HPV 18 DNA in the cellular DNA of the C4-II cervical
      cancer cell line that was established in the USA in 1962 was different from that
      of HeLa cells. These results suggest that the JTC-3, OG and OE cell lines have
      been contaminated by HeLa cells.

PMID- 9556757
TI  - Subcellular localization of hepatitis C virus structural proteins in the liver of
      transgenic mice.
AB  - Hepatitis C virus (HCV) core and envelope proteins are suggested to be
      responsible for the pathogenesis of hepatic and extrahepatic manifestations in
      chronic hepatitis C. Moreover, the core protein is implicated in the regulation
      of the transcription of cellular genes including c-myc, RB and p53. Determining
      the subcellular localization of the core and envelope proteins is therefore
      necessary to elucidate their behaviors, particularly in vivo ones, regarding the
      interaction with transcriptional regulatory proteins or gene elements. We defined
      the subcellular localization of HCV envelope and core proteins which were
      expressed in substantial levels in the liver of transgenic mice. Subcellular
      fractionation by ultra-centrifugation revealed that the envelope proteins were
      present principally in the microsomes of the liver, while a small amount of the
      protein was detected also in the nuclei. Immunohistochemistry confirmed the
      localization of envelope proteins in the nuclei. In contrast, the core protein
      was detected principally in the cytoplasmic fraction, where it was closely
      associated with lipids. A low level of the core protein was detected also in the
      nuclei and microsomal fraction. These results suggest possible interaction of the
      HCV structural proteins with some factors in hepatocytes thereby perturbing
      intracellular circumstances.

PMID- 9556758
TI  - Synthesis and characterization of polymer-(multi)-peptide conjugates for control
      of specific cell aggregation.
AB  - A new synthetic approach has been applied to obtain novel di-, tetra-, and
      (multi)-peptide containing polymer conjugates in quantitative yields with a high
      degree of conjugation. Bis-(N-hydroxysuccinimidyl) esters of PEG (Mw = 200, 600,
      1400, 2000, and 3400) were synthesized and studied in a condensation reaction
      with synthetic peptides: glycine-glycine-tyrosine-arginine (GGYR), a model
      peptide, and glycine-arginine-glycine-aspartic acid-tyrosine (GRGDY), a sequence
      known to promote cell adhesion and aggregation. Tetra-substituted derivatives of
      PEG-based conjugates were synthesized by coupling L-aspartic acid and L-aspartyl
      L-phenylalanine through a condensation procedure in organic media. Poly(acrylic
      acid) and co-polymers (Mw = 2000 and 5000) were studied as a model of
      multifunctional linear polymers in the reaction with L-tryptophan and GGYR.
      Alternative polymer-(multi)-peptide conjugates were successfully synthesized
      using Starburst dendrimer PAMAM (G = 3), 'short' and 'long'-chain PEG-based
      active esters and GRGDY. The structure of the intermediate precursors and peptide
      conjugates was confirmed by spectral (UV-Vis, FTIR, H-NMR) and chromatographic
      (RP-HPLC and SEC) methods. By varying the properties of the interconnecting
      polymer--such as hydrophobicity, molecular weight, and functionality--a set of
      polymer-GRGDY conjugates was synthesized.

PMID- 9556759
TI  - Hepatocyte culture utilizing porous polyvinyl formal resin maintains long-term
      stable albumin secretion activity.
AB  - To investigate the effects of culture conditions on the maintenance of metabolic
      functions of cultured hepatocytes, long-term hepatocyte culture lasting 20 days
      was performed under two different culture conditions, i.e. stationary cultures
      utilizing porous polymer (polyvinyl formal (PVF) resin) as a substratum and
      conventional monolayer dish cultures without PVF. Metabolic activities specific
      to hepatocytes were evaluated in terms of ammonia metabolism, urea synthesis, and
      albumin secretion. Concerning ammonia metabolic and urea synthetic activities, no
      significant differences in maintenance of these activities were found between the
      two culture conditions, and these activities rapidly decreased with the elapse of
      the culture period, especially during the early stage of the experiments.
      However, after day 10, these activities in the stationary cultures were
      maintained at a slightly more favorable level than in the monolayer cultures. On
      the other hand, compared with ammonia metabolism and urea synthesis, stable and
      well-maintained albumin secretion of hepatocytes (60% of the activity in day 1)
      was exhibited in the stationary culture experiments, despite that this particular
      activity under the monolayer culture condition gradually reduced to a very low
      level (5.7% of that on day 1) at the end of the culture. From the morphological
      observations, hepatocytes immobilized in the PVF resin revealed individual
      spherical shapes without forming multicellular aggregation, and it was suggested
      that this characteristic structure contributed to good albumin secretion of
      hepatocytes. In conclusion, the advantages of the hepatocyte culture technique
      utilizing PVF resin over the conventional dish culture in maintaining some
      representative metabolic function specific to hepatocytes were clarified.

PMID- 9556760
TI  - Poly(vinyl alcohol) synthetic polymer foams as scaffolds for cell encapsulation.
AB  - Poly(vinyl alcohol) (PVA) foams were used as scaffolds in hollow fiber membrane
      based cell encapsulation devices. The surrounding permselective membrane serves
      as an immunoisolation barrier while allowing metabolites and other small
      molecules to be freely transported. The internal matrix defines the
      microenvironment for the encapsulated cells. PC12 cell-containing devices
      represent one possible strategy for safe transplantation of dopamine-secreting
      cells for the treatment of dopamine-deficient diseases such as Parkinson's
      disease. PC12 cells--a dopamine-secreting cell line--were encapsulated with PVA
      foam as a matrix material in the lumen of these hollow fibers. In this work, we
      demonstrate the presence of the PVA matrix increased the catecholamine secretion
      efficiency of the cells as compared to devices containing a chitosan matrix.
      Devices were implanted in vivo into rodent striatum and device output of
      catecholamines was measured preimplant and post-explant. Evoked stores of
      dopamine remained constant (preimplant vs explant) for devices encapsulated with
      the foam matrix and increased with devices encapsulated with chitosan matrix.
      Cell proliferation within devices was inhibited in the presence of the foam
      matrix. Cell viability and distribution was significantly improved with the
      inclusion of the foam matrix in both in vitro and in vivo studies. In comparison
      to chitosan--a typical matrix material for PC12 cells--addition of a foam-type
      matrix altered the encapsulated cell microenvironment and resulted in more
      efficient secretion of catecholamines and improved distribution within the device
      resulting in smaller necrotic regions and a lower rate of cell proliferation.

PMID- 9556761
TI  - Cultivation of fibroblast cells on keratin-coated substrata.
AB  - By means of a cell culture method, the attachment and growth of mouse L929
      fibroblast cells were studied on matrices of the (-SDS)- and (+SDS)-keratins,
      which were extracted from wool in the absence and presence of sodium dodecyl
      sulfate, respectively. The (+SDS)-keratin showed some toxic effect on the cell
      growth, but upon washing with a pH 7/phosphate buffer, the protein behaved
      similarly to a substratum of the (-SDS)-keratin. The comparative culture assay on
      the keratins, collagen (type I), and glass revealed that the keratins were more
      adhesive to the cells and more supportive for cell proliferation than the
      collagen and glass. The results were explained by an enhanced initial adsorption
      of mediator proteins from fetal bovine serum onto the keratin substrata.

PMID- 9556762
TI  - Synthesis and characterization of degradable polyurethane elastomers containing
      and amino acid-based chain extender.
AB  - Degradable polyurethane elastomers were synthesized using a diester chain
      extender. The chain extender was synthesized by a diesterification reaction
      between L-phenylalanine and 1,4-cyclohexane dimethanol to yield a diester,
      diamine. Soft segment chemistry (polycaprolactone diol, PCL and polyethylene
      oxide, PEO) and molecular weight were varied and the impact on polyurethane
      physicochemical and degradation characteristics was evaluated. It was found that
      the PEO containing polyurethanes absorbed large amounts of water while the PCL
      containing ones did not, indicating a large difference in bulk hydrophilicity.
      The rate of water vapor permeance (WVP) through the polyurethane films generally
      followed the water absorption trends. However, soft segment crystallinity, noted
      by DSC, for the PCL containing polyurethanes served to reduce WVP values with
      increasing PCL molecular weight. Polyurethane surface characterization was
      carried out by water contact angles and XPS. The PEO containing polyurethanes
      exhibited low contact angles in comparison with the PCL ones. In addition, angle
      resolved XPS demonstrated soft segment surface enrichment in all cases typical
      for phase segregated materials. Significant variation in the physicochemical
      properties of the experimental polyurethanes was observed indicating potential
      use in a variety of biomaterials applications. An in vitro degradation study was
      carried out by incubating the polymers in 0.1 M TBS at 37 degrees C, pH 8.0 for
      up to 56 days. Degradation was followed by measuring mass loss, change in
      molecular weight by GPC and surface alteration by scanning electron microscopy.
      The polyurethane containing PEO was found to exhibit substantial mass and
      molecular weight loss over 56 days resulting in a porous material of little
      strength. In contrast, the PCL containing polyurethane displayed modest mass and
      molecular weight loss after 56 days. This polyurethane retained its strength and
      displayed little surface alteration after 56 days in buffer. It was hypothesized
      that differences in polyurethane hydrophilicity as well as initial molecular
      weight may have been responsible for the dramatic difference in degradation rate
      observed here.

PMID- 9556763
TI  - Mechanical properties of a self-assembling oligopeptide matrix.
AB  - We have begun studies of a novel type of biomaterial derived from a recently
      discovered class of ionic self-complementary oligopeptides. These short peptides
      (typically 8, 16, 24, or 32 amino acid residues with internally-repeating
      sequences) self-assemble in aqueous salt solution into three-dimensional matrices
      capable of favorable interactions with cells, and offer promise for useful
      bioengineering design based on rational changes in sequence. In this paper we
      present preliminary results on mechanical properties, combining experimental and
      theoretical approaches, of one particular example of these peptide materials,
      EFK8. The static elastic modulus was measured using an apparatus designed to
      allow sample fabrication and mechanical testing in the same system with the
      sample in aqueous solution. The material microstructure was examined by SEM and
      the measurements interpreted with the aid of a model for cellular solids. Values
      for the elastic modulus increased from 1.59 +/- 0.06 to 14.7 +/- 1.0 kPa for
      peptide concentrations increasing from 2.7 to 10 mg ml-1. SEM photographs showed
      the microstructure to consist of a relatively homogeneous lattice with fiber
      thickness of 10-30 nm independent of peptide concentration, but with fiber
      density increasing with peptide concentration. This behavior is consistent with
      scaling predictions from the cellular solids model and yields an estimate for the
      individual fiber elastic modulus in the range of 1-20 MPa. We therefore have
      provided some initial physical principles for guiding improvement of the
      mechanical properties of these new materials.

PMID- 9556764
TI  - Left hemispheric specialization for learned, skilled, and purposeful action.
AB  - Three-dimensional motion analyses were performed on trajectories of repetitive
      "slicing" gestures by 4 participants with left-hemisphere lesions and limb
      apraxia, 6 participants with right-hemisphere lesions, and 7 neurologically
      intact participants. Left hemispheric lesioned participants with apraxia, but not
      right hemispheric lesioned participants showed impaired coupling of spatial and
      temporal aspects of wrist trajectories and deficits in interjoint coordination.
      Both groups of brain-lesioned participants differed from control participants in
      the 3-D plane of the wrist motion. The deficits of some right hemispheric
      lesioned participants in controlling the plane of wrist motion may be a
      consequence of left hemispatial neglect with rightward deviations. In contrast,
      the deficits of apraxic participants in controlling wrist trajectories and
      coordinating joint motions seem to reflect a deficit in these participants for
      the movement plan.

PMID- 9556765
TI  - Font-specific priming following global amnesia and occipital lobe damage.
AB  - Font-specificity in visual word-stem completion priming was examined in patients
      with global amnesia and Patient M.S., who had a right-occipital lobectomy. Word
      stems appeared in the same or different font as study words. Amnesic patients
      showed normal font-specific priming (greater priming for words studied in the
      same than different font as test), despite impaired word-stem cued recall.
      Patient M.S. failed to exhibit font-specific priming, despite preserved
      declarative memory. Therefore, perceptual specificity in visual priming depends
      on visual processes mediated by the right-occipital lobe rather than medial
      temporal and diencephalic regions involved in declarative memory.

PMID- 9556766
TI  - Spatial attention deficits in humans: a comparison of superior parietal and
      temporal-parietal junction lesions.
AB  - Although clinical evidence of spatial attention deficits, such as neglect and
      extinction, is typically associated with lesions of the right temporal-parietal
      junction, recent evidence has suggested an important role for the superior
      parietal lobe. Two groups of patients, selected for lesions at the temporal
      parietal junction including the superior temporal gyrus (TPJ group), or for
      lesions involving the parietal but not the superior temporal region (PAR group),
      performed cued-target detection tasks in 2 experiments. An extinction-like
      response time pattern was found for the TPJ but not the PAR group. In addition,
      both groups were able to use expectancy information, in the form of cue
      predictiveness, suggesting that separate mechanisms mediate exogenous and
      endogenous processes during attention shifts.

PMID- 9556768
TI  - Lexical semantic and associative priming in Alzheimer's disease.
AB  - Semantic memory impairment was investigated in patients with probable Alzheimer's
      disease (AD) using a threshold oral word reading task to assess priming of
      different lexical relationships. Healthy elderly controls showed significant
      priming for associatively related nouns (tempest-teapot) and also for nouns
      semantically related either because both designate basic-level exemplars of a
      common superordinate category (cousin-nephew) or because the target names the
      superordinate category of the prime (daughter-relative). AD patients, in
      contrast, showed preserved priming of lexical associates but impaired priming of
      certain semantic relationships. They showed no priming between words designating
      coordinate exemplars within a category, despite preserved priming of the
      superordinate category label. Findings are consistent with the view that at least
      part of the semantic deficit in AD is due to disruption of semantic knowledge
      that affects relationships among basic-level concepts, more than the
      relationships between these concepts and their corresponding superordinate
      category of membership.

PMID- 9556767
TI  - The emergence of spatial rotation deficits in dementia and normal aging.
AB  - The mental rotation required in the Road Map Test of Direction Sense (the "Road
      Map Test"; J. Money, 1976; J. Money, D. Alexander, & H. T. Walker, 1965) has been
      thought to be impaired as a function of age, but not dementia. However, spatial
      rotation in dementia has not been investigated in reference to spatial coordinate
      systems. Patients with dementia (Alzheimer's and ischemic vascular dementias) and
      elderly control participants were administered the Road Map Test. The authors
      analyzed whether the geocentric or egocentric coordinate system determined
      rotation of Road Map Test turns and predicted impairment in dementia patients.
      They found equivalent impairment in both types of dementia, greater angulation
      effect in the geocentric system in patients relative to normal controls, and no
      egocentric effect. Results also suggest early emergence of spatial rotation
      deficit in dementia. Spatial rotation is most often associated with working
      memory, which predicts the correlations found.

PMID- 9556769
TI  - Inhibitory processes in covert orienting in patients with Alzheimer's disease.
AB  - Previous studies of covert orienting in Alzheimer's disease (AD) have
      investigated exogenous and endogenous processes separately. We aimed to
      investigate how the 2 modes of orienting interact to control attention in healthy
      older participants and patients with AD. The covert orienting of visual attention
      task (COVAT) with abrupt onset cues was used in all experiments. In Experiments 1
      and 2, predictive information was added to cues to initiate an endogenous
      orienting response. Results showed that healthy older participants were able to
      use endogenous processes to inhibit exogenous orienting. In contrast, patients
      with AD were unable to inhibit exogenous orienting to cues even when targets
      rarely appeared there. Experiment 3 investigated inhibition of return (IOR) in
      patients with AD. Both healthy older controls and patients with AD showed a
      normal IOR, suggesting that exogenous orienting processes are relatively
      unaffected by the normal aging process or in patients with AD. A model of covert
      orienting in which exogenous and endogenous orienting processes interact to
      control attentional behaviors is discussed.

PMID- 9556770
TI  - Independent effects of Alzheimer's disease on neuropsychological functioning.
AB  - A new analytical procedure, single common factor analysis, was carried out on the
      data from a relatively large sample of normals (n = 101) and patients with
      Alzheimer's disease (AD; n = 180) to examine the extent to which there were
      independent effects of disease status on different neuropsychological variables.
      This technique uses structural equation methods to determine what all of the
      variables have in common, and then controls this common factor when examining the
      relationship between diagnostic group and each individual test variable. To the
      extent that AD represents the sum of independent breakdowns of different
      information processing domains, then there should be sets of variables that have
      weak or nonexistent links to the other variables. However, the results revealed
      that a large proportion of the AD-related effects on test scores was shared and
      was not independent of the AD-related effects on other variables.

PMID- 9556771
TI  - Intact recognition of facial emotion in Parkinson's disease.
AB  - Although the basal ganglia have been shown to be critical for the expression of
      emotion in prosody and facial expressions, it is unclear whether they are also
      critical for recognition of emotions. Selective pathology of parts of the basal
      ganglia is a hallmark of individuals with Parkinson's disease, and such patients
      have been examined in several studies of emotion. We examined 18 patients with
      Parkinson's disease (11 men, 7 women) and 13 age-, education-, gender ratio-, and
      IQ-matched normal controls on their ability to recognize emotions signaled by
      facial expressions. Parkinson's patients performed entirely normally on a
      quantitative task of recognizing emotional facial expressions. The findings do
      not support the notion that the sectors of basal ganglia that are dysfunctional
      in Parkinson's disease are essential for recognizing emotion in facial
      expressions.

PMID- 9556772
TI  - Letter and category fluency in patients with frontal lobe lesions.
AB  - This study examines the hypothesis that patients with frontal lobe lesions are
      impaired on tests of letter but not category fluency. This hypothesis was
      proposed by Moscovitch (1994), based on a series of cognitive studies with young,
      normal participants. A group of patients with lateral prefrontal lesions and age
      matched controls were tested on 2 tests of verbal fluency, the FAS task and a
      category fluency task that used semantic categories as cues (e.g., animals).
      Patients with frontal lobe lesions generated fewer items than controls on both
      letter and category fluency. This effect did not interact with the type of
      fluency test, suggesting that the frontal lobes are more generally involved in
      verbal fluency. Moreover, this pattern of findings, along with previous results
      of impaired free recall and remote retrieval in this patient group, suggests that
      patients with frontal lobe lesions do not efficiently organize and develop
      retrieval strategies.

PMID- 9556773
TI  - Word list learning and prediction of recall after frontal lobe lesions.
AB  - The effect of frontal lobe lesions on the accuracy of prediction of recall in a
      word list learning task was studied. Fifty-nine patients with a focal brain
      lesion and 21 non-brain-damaged control patients memorized a word list by
      selective reminding and predicted before each recall trial the number of words
      they would be able to recall. The patients with left frontal lesions, who were
      inferior to the patients with right frontal lesions and the control patients in
      word list recall, overpredicted their recall more than the other brain-damaged
      patients or the control patients, especially on the 1st trial. The patients with
      right frontal lesions were less accurate in the prediction of recall than the
      patients with right posterior lesions or the control patients.

PMID- 9556774
TI  - Working and strategic memory deficits in schizophrenia.
AB  - Working memory and its contribution to performance on strategic memory tests in
      schizophrenia were studied. Patients (n = 18) and control participants (n = 15),
      all men, received tests of immediate memory (forward digit span), working memory
      (listening, computation, and backward digit span), and long-term strategic (free
      recall, temporal order, and self-ordered pointing) and nonstrategic (recognition)
      memory. Schizophrenia patients performed worse on all tests. Education, verbal
      intelligence, and immediate memory capacity did not account for deficits in
      working memory in schizophrenia patients. Reduced working memory capacity
      accounted for group differences in strategic memory but not in recognition
      memory. Working memory impairment may be central to the profile of impaired
      cognitive performance in schizophrenia and is consistent with hypothesized
      frontal lobe dysfunction associated with this disease. Additional medial-temporal
      dysfunction may account for the recognition memory deficit.

PMID- 9556775
TI  - Factor structure of the Wisconsin Card Sorting Test: dimensions of deficit in
      schizophrenia.
AB  - The aim of this study was to explore the factorial structure of the Wisconsin
      Card Sorting Test (WCST) and to identify the dimensions of deficit in
      schizophrenia. WCST scores in patients with schizophrenia and schizophrenia
      related psychosis (n = 292), 1st degree relatives of schizophrenic patients (n =
      91), and normal controls (n = 141) were subjected to a principal factor analysis
      followed by orthogonal rotation. This led to 3 factors, perseveration, failure to
      maintain set, and idiosyncratic sorting. The detected factor structure was found
      to be invariant across the schizophrenic and control subsamples. Moreover, it
      replicated previous findings from 2 smaller samples. Only perseverations and, to
      a lesser degree, idiosyncratic sorting appeared to differentiate schizophrenic
      patients from comparisons. Only perseveration had good sensitivity and
      specificity, as well as the most robust significant correlations with estimates
      of IQ, attention, and other measures of executive functioning. Thus,
      perseveration appears to be the most diagnostically useful and characteristic
      WCST feature of schizophrenia.

PMID- 9556776
TI  - Neuropsychological outcome following anterior temporal lobectomy in patients with
      and without the syndrome of mesial temporal lobe epilepsy.
AB  - The nature, pattern, and degree of neuropsychological change following anterior
      temporal lobectomy (ATL) were examined as a function of the presence or absence
      of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients
      exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non
      MTLE). The test-retest performance of a group of 40 epilepsy patients who did not
      undergo surgery was used to derive regression-based estimates of test-retest
      change. Overall, the MTLE group did not show significant cognitive decline
      following ATL. In contrast, the left non-MTLE group showed significant declines
      on verbal memory, confrontation naming, and verbal conceptual ability. Further,
      verbal memory was the most substantial area of decline, and was independent of
      seizure outcome. Clinical and theoretical implications of these findings are
      discussed.

PMID- 9556777
TI  - Overview of outcomes research and management and its role in oncology practice.
AB  - Outcomes assessment describes a variety of activities, including classic clinical
      trials with quality of life and cost end points, observational studies examining
      the outcomes of treatment in the course of routine clinical care, and the process
      of managing patterns of care in clinical practice. These activities share
      important common features, including an emphasis on quality of life and economic
      outcomes, an explicit consideration of the importance of patient characteristics
      in determining outcomes, and a broad definition of what constitutes cancer care.
      The primary uses of outcomes data are to evaluate treatments and to assess the
      quality of care provided by physicians, health care institutions, and health
      insurance plans. Outcomes management integrates these activities through the
      implementation of guidelines, ideally based on empiric data on the relationship
      between medical interventions and outcomes; and the measurement of performance
      against a set of quality indicators derived from those guidelines. One of the
      biggest challenges facing clinicians today is how to reconcile the need to do
      what is best for patients with the need to practice cost-conscious medicine. High
      quality outcomes data are at the heart of the solution. This presentation is a
      brief overview of outcomes research and management and its role in oncology
      practice.

PMID- 9556778
TI  - Overview of economic analysis of Le Chevalier Vinorelbine Study.
AB  - The costs and relative cost-effectiveness of different treatments for common
      illnesses are an increasing concern. New treatments for advanced non-small-cell
      lung cancer are having an impact. However, these treatments vary markedly in
      their direct financial costs, toxicity, and quality-of-life profiles. Direct
      comparisons between most combination regimens are not yet completed. Vinorelbine
      (Navelbine) is the first new agent approved in the United States for the
      treatment of metastatic non-small-cell lung cancer in more than a decade. We
      previously reported results of a post-hoc economic analysis that compared the
      anticipated cost-effectiveness of three regimens used to treat non-small-cell
      lung cancer (vinorelbine alone versus vinorelbine plus cisplatin [Platinol]
      versus vindesine plus cisplatin, the assumed standard treatment in Europe).
      Results showed that vinorelbine plus cisplatin was the most effective regimen.
      Using vinorelbine alone as a baseline, vinorelbine plus cisplatin added 56 days
      of life at an additional cost of $2,700, resulting in a cost-effectiveness ratio
      of $17,700 per year of life gained. Similarly, vindesine plus cisplatin added 19
      days of life at a cost of $1,150, or $22,100 per year of life gained. Compared to
      vindesine plus cisplatin, vinorelbine plus cisplatin added 37 days of life at a
      cost of $1,570, or $15,500 per year of life gained. We conclude that the
      incremental cost-effectiveness of the vinorelbine plus cisplatin regimen was less
      than most commonly accepted medical interventions. If vinorelbine is preferred
      because of its favorable toxicity profile, the additional effectiveness of
      cisplatin added substantial efficacy at an acceptable cost.

PMID- 9556779
TI  - Cost-effectiveness of vinorelbine alone or vinorelbine plus cisplatin for stage
      IV NSCLC.
AB  - Le Chevalier and colleagues have reported results of a randomized controlled
      clinical trial comparing vinorelbine alone, versus vinorelbine combined with
      cisplatin, versus standard treatment consisting of vindesine and cisplatin in the
      treatment of patients with advanced non-small-cell lung cancer (NSCLC). Data on
      survival in the three study arms and estimates of the resources used to treat
      these patients were extracted from the publication and inserted into Statistics
      Canada's POpulation HEalth Model (POHEM). This model includes data on diagnostic
      methods, treatment, and outcomes appropriate for stage at presentation, health
      care utilization, and direct care costs ($ Canadian) for best supportive care and
      for several "standard" chemotherapy regimens used to treat advanced NSCLC. POHEM
      was then used to model the cost of care per patient and the total burden of cost
      on the Canadian health care system for each of the chemotherapy treatment
      strategies and for best supportive care. Based on the published survival curves
      for each of the vinorelbine regimens, it was possible to estimate the survival
      gain relative to the standard chemotherapy regimens and to best supportive care,
      and to estimate their cost-effectiveness as cost per life year gained. Based on
      this analysis, the most cost-effective standard regimen relative to best
      supportive care was vinblastine/cisplatin, as it increased average survival while
      reducing costs by $2,846 per case. Vinorelbine/cisplatin increased survival to a
      greater degree, but inpatient administration costs associated with the delivery
      of cisplatin increased treatment costs by $2,983 per case and resulted in a cost
      effectiveness ratio of $6,386 per life year gained. As high-dose cisplatin is not
      routinely administered in the inpatient setting in Canadian institutions,
      estimates were made of the cost of outpatient administration. The cost of
      outpatient care was $55 less per case demonstrating that this is the most cost
      effective way to administer the regimen. Relative to etoposide/cisplatin and
      vinblastine/cisplatin, outpatient vinorelbine/cisplatin proved to be cost
      effective. Various chemotherapy regimens used in the management of advanced NSCLC
      all fall within the boundaries of cost-effectiveness generally accepted for
      health care interventions in Canada. Therefore, cost and cost-effectiveness
      should not be barriers to the utilization of vinorelbine/cisplatin in Canada.

PMID- 9556780
TI  - Quality of life issues in the treatment of metastatic breast cancer.
AB  - The treatment of metastatic breast cancer involves the sequential selection and
      delivery of hormonal therapies and cytotoxic chemotherapies. The available
      therapies for metastatic breast cancer are rarely curative, although high rates
      of response and modest prolongation of survival may be achieved in association
      with varying degrees of treatment-related toxicity. Therefore, the selection of
      appropriate therapy requires a reasoned consideration of the likelihood of
      benefit from therapy balanced with the impact of therapy on the patient's quality
      of life. Several instruments have been developed to measure quality of life in
      cancer patients, but none has been universally accepted, and they require time
      and resources to administer. Few randomized clinical trials have incorporated
      quality of life assessments. Thus, the clinician must balance antitumor activity,
      performance status, and the usual toxicity measures, (e.g., nausea,
      myelosuppression, asthenia) as surrogates for quality of life associated with
      each specific therapy. Studies have confirmed the clinical impression that
      antitumor activity of treatment generally correlates with quality of life
      outcome. The hormonal therapies have the quality of life advantages of limited
      and non-threatening acute toxicity, rare chronic toxicity, need for infrequent
      visits to health care providers, oral administration, and, in appropriately
      selected patients, response and duration of response rates equivalent to those of
      the cytotoxic agents. A number of cytotoxic agents have activity in the treatment
      of metastatic breast cancer. Although the active single agents differ
      substantially in their toxicity profiles, the dose-limiting toxicity is usually
      myelosuppression. Recently, several agents with substantial activity against
      breast cancer have become available, including the taxanes (paclitaxel and
      docetaxel), vinorelbine, and gemcitabine. Oral formulations of vinorelbine are
      being studied that may provide the additional advantages of not requiring
      intravenous access, requiring fewer visits to the health care professional, and
      providing patients with a greater sense of control of their treatment.

PMID- 9556781
TI  - Initial control of chemotherapy-induced nausea and vomiting in patient quality of
      life.
AB  - The side effects commonly experienced by patients receiving chemotherapy for the
      treatment of cancer can challenge many aspects of daily life. Nausea and
      vomiting, the most common side effects reported by patients, affect the ability
      to continue with usual life activities and, thus have a pronounced impact on
      quality of life. This paper reviews studies of the impact of nausea and emesis on
      quality of life, and highlights the importance of prevention of these side
      effects by presenting new data on how persistent uncontrolled nausea and vomiting
      can be. The Morrow Assessment of Nausea and Emesis (MANE) was used to collect
      information on symptoms experienced by consecutive patients starting chemotherapy
      between September 1987 and December 1995 at any of 18 geographically diverse
      member sites of the University of Rochester Cancer Center Community Clinical
      Oncology Program. Data from 1,413 patients were collected after each of four
      successive chemotherapy treatments. Reported incidences of posttreatment nausea
      and posttreatment vomiting after the first treatment were 59.4% and 28.6%,
      respectively. Occurrence of nausea/vomiting at the first treatment was a strong
      predictor of nausea/vomiting at later treatments. Of the 839 patients reporting
      initial nausea, 763 (90.9%) reported nausea at at least one subsequent treatment,
      and approximately 59% reported nausea after all three subsequent treatments.
      Fewer than half (45.6%) of the patients who had no nausea at the first treatment
      developed it later. The majority (72.0%) of patients reporting vomiting at the
      first treatment also reported subsequent vomiting, 30.7% of whom experienced
      emesis at all remaining treatments. Conversely, 76.2% of patients who were emesis
      free at the first treatment remained so for all later treatments. These findings
      show a continuing need for further progress in controlling nausea and vomiting,
      and demonstrate the importance of aggressive nausea/vomiting control at the first
      treatment. In addition, more emphasis on controlling chemotherapy-induced nausea
      after its initial occurrence is necessary.

PMID- 9556782
TI  - Cost-effective use of antiemetics.
AB  - Direct comparison of intravenous and oral 5-HT3 antagonists has shown equivalent
      efficacy if appropriate doses are given, thus allowing widespread use of the more
      convenient and economical oral route. Effective antiemesis generates additional
      cost savings by decreasing the resources necessary for salvage antiemetic
      preparation and administration, additional physician and nursing evaluation,
      clean-up and maintenance of the patient area, and possible additional
      hospitalization necessitated by uncontrolled emesis. If ondansetron and
      metoclopramide are compared strictly on an acquisition cost basis, ondansetron is
      4 to 15 times more expensive. However, if the additional savings attributable to
      better antiemetic control are taken into account, ondansetron is only 2 to 3
      times more expensive and quality of life is markedly improved. In cost-utility
      analysis such improvement in quality of life is taken into account through the
      use of a utility score. Utility scores for antiemetic protection, however, have
      not been well defined. We recently performed a pilot study asking patients
      receiving chemotherapy to rate globally their quality of life (utility score)
      over the preceding chemotherapy cycle, assuming that a small amount of nausea and
      vomiting either had or had not occurred. An incremental utility score of 0.52
      based solely on the presence or absence of nausea and vomiting was identified.
      Further careful investigations to identify the incremental utility resulting from
      use of various modes of oncologic supportive care are required.

PMID- 9556783
TI  - Evolving role of oral chemotherapy for the treatment of patients with neoplasms.
AB  - The past 20 years has seen an increasing trend toward the use of oral
      chemotherapy for the treatment of patients with a variety of malignancies. The
      advantages of oral chemotherapy include lower treatment cost, compared with that
      of intravenous (i.v.) administration, and more convenient treatment for patients.
      Several oral drugs are now used routinely for cancer treatment, and others are
      under investigation. Hormonal agents, such as tamoxifen, flutamide, and megestrol
      acetate, and antimetabolites, such as hydroxyurea, which are available only in
      oral formulation, have proven both safe and efficacious. Several other oral
      drugs, including etoposide and cyclophosphamide, have been shown to be useful and
      often as effective as their i.v. formulations, and more data on the
      bioavailability of these agents have become available. In addition, several new
      and promising oral agents (platinum compounds, fluorinated pyrimidines,
      topoisomerase I inhibitors, and others) are likely to be introduced into clinical
      practice in the near future. It is possible that eventually, oral combination
      chemotherapy will be an accepted and standard approach for the treatment of
      patients with many types of cancer.

PMID- 9556784
TI  - Improving 5-FU with a novel dihydropyrimidine dehydrogenase inactivator.
AB  - GW776C85 is a new drug that has been shown to be an effective inactivator of
      dihydropyrimidine dehydrogenase (DPD). Preclinical studies demonstrated that
      administration of GW776C85 with 5-fluorouracil (5-FU) resulted in several
      desirable pharmacologic effects. Initial clinical data on 5-FU combined with
      GW776C85 suggest potentially increased antitumor activity in at least some
      malignancies with tolerable toxicity, as well as several distinct economic and
      quality-of-life advantages including the following: (1) The possibility of
      administering 5-FU as an oral drug due to excellent bioavailability of 5-FU
      following inactivation of DPD; (2) a cost-effective alternative to continuous or
      protracted infusion of 5-FU without the need for hospitalization or surgical
      placement of an intravenous access and availability of an ambulatory pump; and
      (3) potential for less interpatient variation of 5-FU toxicity (e.g., in host
      tissues, such as bone marrow and gastrointestinal mucosa cells) due to
      inactivation of DPD in essentially all patients treated, permitting better 5-FU
      dosing guidelines. Finally, because tumors may theoretically become resistant to
      5-FU by increased levels of DPD, the use of GW776C85 to inactivate DPD may
      provide a potential means by which tumor resistance can be reversed.

PMID- 9556785
TI  - Phase II and III clinical trials of toremifene for metastatic breast cancer.
AB  - Toremifene (Fareston) received FDA approval in 1997 for the first-line treatment
      of postmenopausal women with estrogen receptor (ER)-positive or -unknown
      metastatic breast cancer. Phase II and III trials have demonstrated that first
      line therapy with toremifene, 60 mg/d, is as effective and as well tolerated as
      tamoxifen (Nolvadex), 20 or 40 mg/d, in such patients. To date, phase III trials
      have failed to show a statistically significant advantage of higher toremifene
      doses over standard doses of tamoxifen in these women. Studies appeared to
      indicate minimal efficacy of high toremifene doses in women with ER-negative
      tumors, but the number of patients studied was small. Although results of some
      trials of high-dose (240 mg/d) toremifene in tamoxifen-"refractory" patients were
      negative, other trials that included prolonged (> or = 6 months) stable disease
      as an indication of clinical benefit yielded positive results.

PMID- 9556786
TI  - Antiestrogen therapy: uncertainties and risk assessment.
AB  - Tamoxifen is by far the most clinically tested antiestrogenic drug currently used
      as adjuvant therapy for breast cancer and it continues to provide considerable
      benefit in this setting. The balance from clinical trials indicates a strong
      association between the use of tamoxifen and an increase in uterine tumors (three
      to sixfold). In rats, tamoxifen is a mutagenic, genotoxic hepatocarcinogen. These
      actions are not related to its estrogen antagonist activity but have been shown
      to be as a result of metabolic activation of this drug by cytochrome P450
      enzymes, resulting in irreversible binding to cellular DNA. The mechanism of
      endometrial cancer associated with tamoxifen treatment is unclear, although there
      are two plausible hypotheses: (1), tamoxifen causes damage and mutation to DNA in
      uterine cells or (2), it promotes the development of endometrial tumors through
      its estrogen agonist activity. The evidence for a genotoxic effect of tamoxifen
      in the uterus is highly contentious and, on balance, we have concluded that it is
      more likely that the estrogenic effects of tamoxifen promote tumor development.

PMID- 9556787
TI  - Adjuvant trials of toremifene vs tamoxifen: the European experience.
AB  - When results from the phase II trials of toremifene (Fareston) and tamoxifen
      (Nolvadex) in metastatic breast cancer were published, the Finnish Breast Cancer
      Group began to plan the first trial of toremifene in an adjuvant setting. This
      multicenter, randomized trial is comparing toremifene (40 mg/d) to tamoxifen (20
      mg/d) in postmenopausal lymph node-positive breast cancer patients. Treatment
      duration is 3 years. About 1,150 of a planned 1,460 patients have been enrolled
      to date. The International Breast Cancer Study Group is also conducting two
      adjuvant trials evaluating 5 years of toremifene (60 mg/d) vs tamoxifen (20
      mg/d). More than 1,000 patients have been enrolled in these studies to date. The
      efficacy of toremifene is being explored in all of these trials. In the Finnish
      trial, additional protocols are evaluating treatment side effects, including the
      formation of DNA adducts in the endometrium and leukocytes, certain ocular
      problems, thromboembolic events, and subjective side effects. The effects of
      toremifene on lipid levels and bone density are also being studied. An interim
      safety analysis, performed in the Finnish study after 500 patients were enrolled
      (mean follow-up, 18 months), showed no significant differences between toremifene
      and tamoxifen in terms of efficacy or side effects. Toremifene seems to be well
      tolerated and may have additional positive effects. Ongoing trials will soon
      reveal how beneficial toremifene is in the adjuvant setting and whether it is
      devoid of the adverse effects observed with tamoxifen.

PMID- 9556788
TI  - Status of antiestrogen breast cancer prevention trials.
AB  - Various ongoing double-blind clinical trials are evaluating the use of tamoxifen
      (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy
      women have been randomized to these trials, and it should be possible, by the
      year 2000, to detect any preventive effect of tamoxifen in healthy women.
      Furthermore, with the large numbers of women involved, it should be possible to
      evaluate prevention in subgroups of participants according to risk of the
      disease, particularly those women carrying high-risk genes, such as BRCA1 and
      BRCA2. Adverse effects of tamoxifen have been identified, including a transient
      bone loss in premenopausal women and uterine effects, including polyps, cysts,
      and endometrial cancer, in postmenopausal women. Although the potential benefit
      of tamoxifen in preventing breast cancer in healthy women is likely to outweight
      any potential long-term risks, the use of other tamoxifen-like drugs, such as
      raloxifene (Evista) and toremifene (Fareston) is now being investigated.

PMID- 9556789
TI  - Emerging role of aromatase inhibitors in the treatment of breast cancer.
AB  - The new generation of potent steroidal and nonsteroidal inhibitors of the enzyme
      aromatase act by decreasing estrogen production throughout the body in
      postmenopausal women. The most potent of these agents may also inhibit estrogen
      synthesis within metastatic breast cancer tissue. The newly developed, orally
      administered, nonsteroidal competitive inhibitors, such as anastrozole
      (Arimidex), letrozole (Femara), and vorozole (Rizivor), are a thousand times more
      potent inhibitors of aromatase than is aminoglutethimide. Furthermore, these
      agents are highly selective. In several large randomized trials, the new
      inhibitors produced similar response rates as megestrol acetate (160 mg/d) in
      postmenopausal women with hormone-dependent breast cancer, but showed a trend
      toward improved response duration and survival. They also produced less weight
      gain and fewer cardiovascular and thromboembolic side effects. In addition,
      letrozole proved superior to aminoglutethimide in another randomized trial. Both
      anastrozole (1.0 mg/d) and letrozole (2.5 mg/d) have now been approved as second
      line treatment for hormone-dependent breast cancer in postmenopausal women in
      whom disease has progressed following tamoxifen treatment. Either drug should
      replace the routine use of megestrol acetate in this setting. Ongoing clinical
      studies are comparing anastrozole and letrozole to antiestrogens as first-line
      endocrine therapy for metastatic breast cancer. Other trials will study the
      possible roles of these compounds as adjuvant therapy and chemoprevention for
      breast cancer.

PMID- 9556791
TI  - Pivotal trials of letrozole: a new aromatase inhibitor.
AB  - Letrozole (Femara) is a nonsteroidal aromatase inhibitor that is approximately
      10,000 times as potent as aminoglutethimide in vivo. Two pivotal multinational
      phase III trials have compared letrozole (0.5 and 2.5 mg/d) against megestrol
      acetate and aminoglutethimide, respectively, in patients with locally advanced or
      metastatic breast cancer. The letrozole vs megestrol acetate trial showed the
      superiority of letrozole (2.5 mg/d) over megestrol acetate with respect to
      response rate, response duration, duration of overall clinical benefit (complete
      response plus partial response plus stable disease > or = 6 months), time to
      progression, and time to treatment failure. The letrozole-treated patients also
      showed a nonsignificant trend toward better survival. In the letrozole vs
      aminoglutethimide trial, letrozole (2.5 mg/d) was significantly superior in terms
      of duration of overall clinical benefit and survival. There were also strong
      trends favoring letrozole with regard to objective response rate and duration of
      response. Unexpectedly, both trials demonstrated a dose-response effect for 2.5
      mg of letrozole over 0.5 mg in terms of response and overall survival. This
      finding raises the possibility that intratumoral aromatase suppression may be
      more relevant in breast cancer therapy than are plasma estrogen levels.

PMID- 9556790
TI  - Preclinical studies using the intratumoral aromatase model for postmenopausal
      breast cancer.
AB  - To determine the most effective strategies for the treatment of postmenopausal
      hormone dependent breast cancer, we recently developed a model system in nude
      mice. In this model, estrogen receptor-positive human breast cancer cells (MCF-7)
      stably transfected with the aromatase gene are inoculated into ovariectomized,
      immunosuppressed (nude) mice. These cells synthesize sufficient estrogen from
      androgen substrate to stimulate their proliferation and the development of
      tumors. Moreover, estrogen secreted by the tumor cells maintains uterine weight
      comparable to that of the intact mouse. In the present study, we employed this
      model to investigate the effects of the aromatase inhibitor, letrozole (CGS 20267
      [Femara]) on mammary tumor growth and on the uterus. We also used this model to
      predict the effects of combining two aromatase inhibitors, letrozole and
      anastrozole (Arimidex), with the antiestrogen tamoxifen (Nolvadex). Letrozole was
      found to be a highly potent inhibitor of tumor proliferation and more effective
      than tamoxifen. No stimulation of uterine growth was observed with the aromatase
      inhibitors. However, the combination of letrozole or anastrozole and tamoxifen
      was no more effective than either aromatase inhibitor alone. The agonistic effect
      of tamoxifen on the uterus was observed when it was given alone and when combined
      with the aromatase inhibitors. Furthermore, letrozole had the most potent
      antitumor activity when compared to other aromatase inhibitors and antiestrogens.
      No additional benefit was observed by combining these agents with tamoxifen over
      treatment with aromatase inhibitors alone.

PMID- 9556793
TI  - [Molecular genetics of epithelial ovarian neoplasms: correlations with phenotype
      and biological behavior].
AB  - The phenotypic variability of epithelial ovarian neoplasms correlates with a
      diversity of changes on the molecular level. Invasive serous and undifferentiated
      ovarian carcinomas are characterized by p53 mutations, extensive loss of genetic
      material of chromosome 17 and complex changes on many other chromosomes. These
      alterations are seen only in a minority of mucinous and endometrioid carcinomas,
      mainly in advanced stages. Overexpression of bcl-2 is seen most frequently in
      endometrioid carcinomas (ca. 90% of cases), which in addition show microsatellite
      instability in around a third of cases, as has been described in endometrioid
      endometrial carcinomas. KRAS mutations are characteristic for mucinous LMP tumors
      (borderline tumors) and mucinous carcinomas (40-50% of cases). Furthermore, KRAS
      mutations have been described in around a third of serous LMP tumors, which in
      addition show microsatellite instability in up to 40% of cases. Serous LMP tumors
      never harbour complex chromosomal aberrations.

PMID- 9556792
TI  - [Value of basement membrane imaging in diagnosis of invasive carcinomas].
AB  - The destruction of the epithelial basement membrane is widely regarded as a clear
      criterion for invasive malignant tumor growth. Since, however, defects in the
      basement membrane may also occur in non-invasive conditions, such as inflammatory
      and proliferative lesions, and since it has been shown that particularly in
      highly differentiated squamous cell carcinomas a continuous basement membrane is
      mimicked by the presence of isolated components, this criterion seems to be of
      minor value for the diagnosis of malignancy. Despite these drawbacks, the
      immunolocalization of basement membrane material may still be of differential
      diagnostic significance in certain situations. This holds particularly true for
      invasive (ductal) breast carcinomas, which usually completely lack a basement
      membrane. Accordingly, sclerosing adenosis can be distinguished from invasive
      carcinoma, as a distinction can be made between neoplastic (malignant) tubular
      formations and reactive lesions.

PMID- 9556794
TI  - [Oncocytic metaplasia/neoplasia--morphology, biochemistry, molecular genetics].
AB  - The article gives a review on oncocytic metaplasia and oncocytic tumors.
      Biochemical, cytochemical and molecular genetic findings are discussed. It has
      been established, that defects of the respiratory chain occur predominantly in
      oncocytic foci of the parathyroids and the liver. The underlying molecular
      genetic mechanisms are still unclear, however. In particular, one has to assume
      that oncocytic metaplasia differs pathogenetically from oncocytic neoplasia.
      Furthermore, organ-dependent prognostic differences of oncocytic tumors exist.
      Oncocytic carcinomas are predominantly seen in the thyroid and are scarce in
      other organs. The molecular genetic basis of this phenomenon is, however, still
      unknown.

PMID- 9556795
TI  - [Heterogeneity of seminal vesicle amyloid. Immunohistochemical detection of
      lactoferrin and amyloid of the prealbumin-transthyretin type].
AB  - Localized depositions of amyloid in the seminal vesicles may occur in elderly
      men. Earlier immunohistochemical studies have failed to identify immunoreactivity
      of known amyloid material. In this autopsy study, all seminal vesicles of males
      older than 50 years were histologically examined to determine incidence and
      phenotype of seminal vesicle amyloidosis. Seven out of 50 patients (14%) showed
      depositions of amyloid in the seminal vesicles. These amyloid depositions as well
      as one additional case were characterized histochemically, immunohistochemically
      and electronmicroscopically. All but two of these patients (75%) showed
      simultaneously amyloid depositions in the heart. Lactoferrin immunoreactivity was
      found in 6 patients (75%). Lactoferrin is an iron-binding, bacteriostatic
      glycoprotein, which is produced in the seminal vesicles. Four patients with
      lactoferrin positive amyloid in seminal vesicle showed different amyloid
      depositions in the heart (immunoglobulin light chain amyloid AL-lambda). Two
      cases (25%) showed the same amyloid type in heart and seminal vesicles
      (prealbumin-transthyretin type amyloid). Our study shows that most amyloidoses of
      the seminal vesicles are organ-limited depositions of lactoferrin. These forms of
      localized amyloidosis have to be separated from senile systemic amyloidosis with
      seminal vesicle involvement.

PMID- 9556796
TI  - [Numerical chromosome aberrations in abortion tissue. Comparison of conventional
      cytogenetics and interphase cytogenetics in paraffin sections and nuclear
      suspensions].
AB  - Chromosomal aberrations are an important cause of spontaneous abortions. In order
      to detect numerical aberrations, paraffin-embedded tissue from 26 abortions with
      known conventional cytogenetic findings (CCG; 25 numerical aberrations and one
      partial trisomy 7p) was analyzed by means of interphase cytogenetics (ICG) using
      centromer-specific DNA probes for chromosomes #X, #Y, #10, #18, and #13/#21.
      Limit-values for the diagnosis of aneusomy in tissue sections were established by
      classifying the distribution of hybridization signals by CCG data (for gain > or
      = 15% of nuclei with +1 signal; for deletion > 40% of nuclei with -1 signal).
      Signal distribution in tissue sections and nuclear suspensions from paraffin
      blocks analyzed in parallel showed statistically a highly significant correlation
      (P < 0.0001). ICG and CCG diagnoses corresponded in 18 of 20 cases suitable for
      evaluation (90%; no false-positive result). No correlation between cytogenetic
      and histologic findings could be found. ICG proved to be a reliable tool for the
      detection of numerical chromosomal aberrations in paraffin-embedded tissue of
      abortions (sections and nuclear suspensions). This, data for genetic counselling
      of the parents can be provided. The limit values for diagnosis of aneusomy could
      also be important for the application of ICG in tumor cytogenetics.

PMID- 9556797
TI  - [Chronic transplant reaction of the kidney. A interphase cytogenetic and
      immunohistologic characterization of the involved cells in relation to donor and
      recipient origin].
AB  - Chronic rejection is a major problem in contemporary kidney transplantation. The
      purpose of this study was to determine whether renal cells are repopulated by
      extra-renal cells over time or whether the graft remains permanently allogenic.
      We studied nine explanted allografted kidneys of sex-mismatched donors by means
      of non-isotopic in situ hybridization (NISH). We used biotinylated centromer
      specific DNA probes of the human chromosomes Y and X. In a further step,
      monoclonal and polyclonal antibodies against CD45, CD3, CD20, CD31, CD1a, S100,
      alpha-actin, factor Vill and UEA were used to analyse the various infiltrating
      cell types and the cells involved in allograft arteriopathy. In several cases
      NISH and immunohistochemistry were combined to facilitate the typing of cells.
      Our study showed that up to several years after transplantation the glomerular,
      tubular and endothelial cells retained donor origin. The only cells of recipient
      origin were the inflammatory cells, predominantly macrophages and T lymphocytes.

PMID- 9556798
TI  - [Placentoid malformation of the lung].
AB  - The differential diagnosis of bullous and cystiform lung alterations comprises a
      relatively calculable number of various diseases, in which the most important are
      rare cystic tumors and congenial malformations, such as adenomatoid cystic
      malformation. We report on a rare clinical picture. In this case, the clinical
      diagnosis of localized unilateral emphysema caused by local displacement and with
      subsequent complications had led to "bullectomies" and pneumonectomy.
      Macroscopically, spongiform solid areas in association with areas of physaliform
      transformation were seen, corresponding histomorphologically to villous,
      placentalike formations. The "villous stroma" revealed focally regressive
      alterations, fatty islets and leiomyomatous areas. So far, the pathogenesis of
      this lesion, described as "placentoid malformation" due to its pathognomonic
      histological appearance, remains unclear. In contradiction to the much discussed
      hypothesis that this lesion may develop from pre-existing lung emphysema, our
      results suggest that this may be an independent lesion, possibly congenital
      hamartous malformation with self-developing progression. The clinically
      predominant emphysematic alterations are considered to be caused by a valve
      mechanism due to unphysiological traction forces, the lymphatic pathways
      regularly found in the border areas towards the original lung tissue, possibly
      playing an important etiological part.

PMID- 9556799
TI  - [Fibrillary glomerulonephritis. Case report for differential nephrotic syndrome
      diagnosis].
AB  - A 67-year-old male patient presented with a nephrotic syndrome. Biopsy of the
      kidney revealed the characteristic of fibrillary glomerulopathy on light and
      electron microscopy. Other non-nephritic causes of a nephrotic syndrome (e.g.
      amyloidosis, immunotactoid glomerulopathy, light-chain glomerulopathy,
      cryoglobulinaemia, collagen-III glomerulopathy, fibronectin glomerulopathy) could
      be excluded. Besides the case report, differential diagnosis of fibrillary
      glomerulopathies is presented.

PMID- 9556800
TI  - [Leiomyosarcoma of the spermatic cord with paraneoplastic beta-hCG production].
AB  - Leiomyosarcomas of the spermatic cord are very rare tumours, which, in contrast
      to the rhabdomyosarcoms of childhood, occur almost exclusively in adults. We
      report the case of a 51-year-old male patient with a metastasizing, pleomorphic
      leiomyosarcoma of the spermatic cord. The tumour showed paraneoplastic secretion
      of beta-chain human chorionic gonadotropin (beta-hCG), as was demonstrated by the
      elevated levels of beta-hCG in serum samples and by immunohistochemistry.
      Histologically, the tumour was a high-grade leiomyosarcoma which showed an
      aggressive course with pulmonary metastases appearing 4 months after primary
      surgery. A concomitant rise in the serum levels of beta-hCG was also noted at
      this time. A wide spectrum of tumours with a choriocarcinomatous component or
      paraneoplastic production of beta-hCG has been described, the vast majority being
      carcinomas. Only two leiomyosarcomas producing beta-hCG have so far been
      reported. The paraneoplastic production of beta-hCG should prevent confusion with
      germ-cell tumours, especially teratomas.

PMID- 9556801
TI  - [Coincidence of balloon cell melanoma with balloon cells in a dermal nevus].
AB  - We report a coincidence of balloon cell melanoma and balloon cell transformation
      in a dermal nevus of a 56 years old female patient. The foamy cells in both
      tumors with different dignity expressed S-100 and Vimentin. HMB45 was expressed
      in all balloon cells of the melanoma. Detection of HMB45 in some of the nevus
      associated balloon cells was considered as an expression of cellular activation.

PMID- 9556802
TI  - [Primary primitive neuroectodermal tumor of the urinary bladder.
      Clinicopathologic case report and differential small cell tumor diagnosis of this
      site].
AB  - We report a rare case of primary primitive neuroectodermal tumour of the bladder
      in an adult. A huge tumour with extensions into pelvic and retroperitoneal tissue
      was found radiologically in a 62-year-old man. The patient did not complain about
      remarkable clinical symptoms until 4 days before admission to hospital. Histology
      of diagnostic transurethral tumour resection showed a small round-cell tumour
      with focal necrosis and scattered Homer-Wright rosettes. Immunohistochemical
      analysis revealed that tumour cells stained positively with 013, a monoclonal
      antibody which recognizes the membrane glycoprotein p30/32MIC2. Focally, tumour
      cells stained positively for vimentin, NSE, S-100 protein and synaptophysin. The
      patient died 3 weeks later because of fulminant pulmonary embolism and autopsy
      revealed a huge, partly exophytic but mainly endophytic tumour of the bladder
      with extensions into the rectum and retroperitoneal tissue. The differential
      diagnosis of small round-cell tumours in this location is discussed.

PMID- 9556804
TI  - [Diagnostic imaging of the larynx. Normal anatomy of the regional spread of
      pathologic changes].
AB  - The primary goal of diagnostic imaging of the larynx is analysis of submucosal
      structures that are not visible by clinical or endoscopic means. Therefore, image
      analysis of the larynx should only be performed under knowledge of the results of
      clinical diagnosis. The anatomic relationships of the laryngeal skeleton, the
      intrinsic structures, and the surrounding soft tissue are presented synoptically.

PMID- 9556803
TI  - [Physiology of the larynx].
AB  - The larynx consists of the cartilaginous-osseous framework, elastic membranes and
      ligaments, joints, muscles, nerves, vessels, and interior cavity. The laryngeal
      functions are the protection of the airway during swallowing, respiration (i.e.
      maintainance of the airway) and phonation. During the pharyngeal phase of
      swallowing the swallow reflex induces a laryngeal closure in three levels and a
      superior-anterior movement of the larynx and hyoid bone. The laryngeal airway is
      maintained by the circumference of the cricoid cartilage. Phonation is the
      phylogenetically recent function of the larynx and was made possible by the
      laryngeal descent. The sound production is explained according to the myoelastic
      aerodynamic theory. The diagnostics of laryngeal diseases is performed in close
      cooperation between otorhinolaryngology and radiology. For diagnostic purposes,
      the physiology of the larynx requires to take into account not only
      morphological, but also functional aspects.

PMID- 9556805
TI  - [Rational imaging strategies in laryngeal diseases].
AB  - Clinical information is indispensable for swift and cost-effective clarification
      of diseases of the larynx. While quality clarification of neurological changes in
      the area of the posterior cranial fossa and in the course of the vagus nerve as a
      cause of glottis malfunction is possible with MRI, localized disease of the
      larynx can more effectively be assessed with low-artifact CT. In the particularly
      difficult assessment of the post-operative larynx, a recurrence can be diagnosed
      only after a baseline study has been carried out after the end of therapy. With
      knowledge of the pretherapeutic findings, the findings immediately post-therapy,
      and the operation technique used, the optimal CT examination, which can be
      carried out quickly, will be able to provide more information about recurrence.

PMID- 9556806
TI  - [Diagnosis and therapy of laryngeal carcinoma].
AB  - Therapeutic choice in laryngeal carcinoma is influenced by the nature of the
      tumor and a variety of factors involving the patient and physician. Small (T1)
      and exophytic (T1, T2) tumors are suitable for radiotherapy. Limited lesions (T1,
      T2) can be cured by functional endoscopic resection techniques or external
      partial laryngectomies. Extensive tumors (large T2; T3) are treated by total
      laryngectomy or by primary irradiation, especially in the case of a good response
      to induction chemotherapy. When radiation treatment fails, surgery succeeds in
      more than half of the cases. Tumors infiltrating or transgressing the laryngeal
      framework (T4) can only be cured by total laryngectomy followed by radiotherapy.
      Subtotal or circular ablation of the adjacent pharynx or esophagectomy needs
      repair with visceral or myocutaneous grafts. Lymphatics are preferentially
      treated with the same modality as used in the primary disease. Inconspicuous
      lymphatics should be treated electively in most cases, with the exception of
      early glottic cancer.

PMID- 9556808
TI  - [Stroboscopy and imaging in interdisciplinary diagnosis of early stages of
      laryngeal carcinoma].
AB  - The laryngostroboscopy is regarded to be the most important functional
      investigation in laryngologic and phoniatric diagnostics. She allows an analysis
      of vocal fold vibrations during phonation. Stroboscopic evaluations permit to
      early detect infiltrative processes of the vocal folds. Superficial alterations
      of the mucous membrane that invade into the muscle cause a phonatory "standstill"
      of the vocal fold in the stroboscopy, i.e. a complete lack of vibratory motion.
      If such a phonatory standstill persists for more than 2 or 3 weeks, a biopsy via
      microlaryngoscopy is indicated for diagnostic purposes. In comparison to
      stroboscopy, imaging techniques are not of such great significance in early
      laryngeal cancer. But in case of suspected infiltration of the tumor a further
      diagnostic evaluation with CT or MRI is necessary to detect possible neoplastic
      invasion of the laryngeal cartilage or of extralaryngeal structures. In this
      paper, we present the principle of laryngostroboscopy, the examination procedure
      and the stroboscopic parameters. Case reports of early laryngeal cancer
      illustrate the interdisciplinary diagnostic procedure with CT, MRI and
      stroboscopy.

PMID- 9556807
TI  - [Diagnosis and staging of laryngeal tumors with CT and MRI].
AB  - Cross-sectional imaging with CT and MRI plays an indispensable complementary role
      to endoscopy in the pretherapeutic workup and staging of laryngeal neoplasms.
      Adequate interpretation of the CT and MR images requires a thorough knowledge of
      the patterns of submucosal spread and familiarity with the diagnostic signs of
      neoplastic invasion as seen with each modality. In addition, the radiologist
      should be aware of the implications of imaging for staging and treatment. Both CT
      and MR imaging are highly sensitive for the detection of neoplastic invasion of
      the pre-epiglottic space, paraglottic space, subglottic region and cartilage. The
      high negative predictive value of both CT and MRI allows exclusion of neoplastic
      cartilage invasion quite reliably. The specificity of both CT and MRI is,
      however, limited and both methods may therefore overestimate the extent of tumor
      spread. Nevertheless, both cross-sectional imaging methods significantly improve
      the pretherapeutic staging accuracy of laryngeal tumors if used in addition to
      clinical examination and endoscopic biopsy. In the presence of a submucosal mass,
      CT and MRI play a key role for the diagnosis, as they may characterize the
      lesion, reliably depict its submucosal extent, and guide the endoscopist of
      perform deep biopsies that allow a definitive histological diagnosis.

PMID- 9556810
TI  - [Postoperative complications after larynx resection: assessment with video
      cinematography].
AB  - In past decades, the surgical techniques for treating laryngeal carcinoma have
      been vastly improved. For circumscribed tumors, voice-conserving resections are
      possible and for extensive neoplasms, radical laryngectomy, sometimes combined
      with chemoradiation, has been developed. Postoperative complications regarding
      swallowing function are not uncommon. Radiologic examinations, especially
      pharyngography and videofluoroscopy, are most often used to evaluate patients
      with complications after laryngeal surgery. An optimized videofluoroscopic
      technique for evaluation of complications is described. The radiologic appearance
      of early and late complications, such as fistulas, hematomas, aspiration,
      strictures, dysfunction of the pharyngoesophageal sphincter, tumor recurrence,
      and metachronous tumors is demonstrated.

PMID- 9556809
TI  - [Function preserving surgical therapy of head-neck tumors with the CO2 laser].
AB  - The use of microscopically controlled laser surgery to treat tumors of the upper
      aerodigestive tract has as a function maintaining form of treatment gained
      significance. It is an alternative to conventional surgery, which often makes
      organ removal necessary. We report on our experience with 85 patients who
      underwent a laser surgical resection of malignomas of the upper aerodigestive
      tract. The aim of transoral laser surgery is a histologically confirmed radical
      tumor resection. Tumor resection can be individually adapted according to the
      tumor extent. An unnecessary resection of cartilage and muscles can be avoided.
      Provided the appropriate indication is given, laser surgery yields good oncologic
      and excellent functional results.

PMID- 9556811
TI  - [Pathologic swallowing pattern after tumor surgery of oro- and hypopharynx.
      Analysis with differentiated deglutition imaging].
AB  - Dysphagia is a common complaint following surgical intervention in the oral
      cavity and hypopharynx, often leading to prolonged postoperative recovery.
      Videofluoroscopy allows detailed visualization of deglutition, demonstrating the
      morphology as well as the functional aspects. Therefore, videofluoroscopy
      provides the basis for further therapeutic management. We discuss the pathology
      of deglutition in 19 patients recovering from tumor surgery of the oro- and
      hypopharynx. In most cases the results demonstrated severe impairment of both the
      oral and pharyngeal phase of deglutition. Our data emphasize the importance of
      the oral phase of deglutition for preparation and initiation of the following
      phases.

PMID- 9556812
TI  - [Functional spiral CT in after-care of irradiated laryngeal carcinomas].
AB  - The importance of spiral-CT is clinically accepted for diagnosing spreading
      disease and for making a decision about the therapy strategy for head and neck
      tumors. Its importance for follow-up after radiotherapy was examined in 26
      patients with irradiated laryngeal tumors. Using spiral-CT multiple signs of
      alterations (n = 98) can be diagnosed, which are not only important for tumour
      relapse, but also for assessment. Spiral-CT offers the possibility of achieving
      various additional information about the larynx that cannot be obtained with
      laryngoscopy. In follow-up examinations after radiation, laryngoscopy and spiral
      CT are recommended as an integrated neck examination using the breath-holding
      technique (separately reconstructed) and also as functional spiral-CT of the
      vocal cords in "I"-phonation.

PMID- 9556814
TI  - [Septic focus in the retroperitoneum--iatrogenic foreign body of cotton
      (gossypiboma)].
AB  - Retained surgical towels (gossypiboma) present a diagnsotic problem if they
      remain asymptomatic for many years. We report on one 51 year old patient with
      repeated septic temperatures in the early post-operative phase after
      hemicolectomy. The contrast enhanced CT of the abdomen revealed a well-defined
      round soft-tissue mass with a dense, enhanced wall containing an internal high
      density wavy and striped area. At laparotomy a secondary infected surgical sponge
      with abscess formation was found.

PMID- 9556813
TI  - [Punch biopsy or fine needle aspiration biopsy in percutaneous lung puncture?].
AB  - PURPOSE: The diagnostic accuracy and rate of complications of CT-guided core
      biopsies (CB) from suspected tumors of the chest were compared to the accuracy a
      complications of fine-needle aspiration biopsies (FNAB). METHODS: The accuracy in
      the diagnosis of a benign or malignant lesion of 79 FNAB (19.5 G self-aspirating
      cutting needle) and of 83 CB (18 G automated core biopsy) and the rates of
      pneumothorax, pleural drainage and hemoptysis were retrospectively evaluated.
      RESULTS: With FNAB, the sensitivity for malignant lesions was 62.1% and the
      accuracy 68.4%. With CB the sensitivity amounted to 85.9% and accuracy to 86.7%.
      The rate of pneumothorax was 25.3% following FNAB, with a drainage rate of 5.1%
      compared to 19.3% and 6.0%, respectively, following CB. The rate of pneumothorax
      and drainage increased with increasing path length through aerated lung. In
      advanced emphysema, the pneumothorax rate did not increase; however, in
      pneumothoraces, pleural drainage was mandatory in 20% of FNAB and in 100% of CB.
      Hemoptysis without any therapeutic consequences occurred in 3.8% following FNAB
      and in 6.0% following CB. CONCLUSIONS: With CB diagnostic accuracy can be clearly
      increased without an obvious increase in the complication rate. However, in
      patients with obvious emphysema, the pleural drainage rate of pneumothorax may be
      higher following CB.

PMID- 9556815
TI  - The influence of occlusive dressing and hyperbaric oxygen on flap survival and
      the healing of ischaemic wounds.
AB  - The effect of dressing with Duoderm (hydrocolloid) and treatment with hyperbaric
      oxygen was investigated on the healing of ischaemic incisional wounds and on flap
      survival in rats. After 10 days, Duoderm dressing of ischaemic wounds decreased
      all strength parameters (load*S, stress*S) by 41%-44% and the improvement of
      ischaemic wound healing by hyperbaric oxygen treatment shown in our previous
      study was not seen. After removal of Duoderm on day 10 the biomechanical
      properties had improved but not returned to normal on day 20. In the dressed
      animals the shrinkage of ischaemic wounds and the extension of necrosis on the
      ischaemic flaps were reduced. Dressing may be useful clinically in preventing
      superficial dermal necroses. One must, however, be aware of the impairment of the
      wound strength of the incisional wounds.

PMID- 9556816
TI  - The effect of recombinant basic fibroblast growth factor (bFGF) in fibrin
      adhesive vehicle on the healing of ischaemic and normal incisional skin wounds.
AB  - Normal and ischaemic incisional wounds in rats were treated with recombinant
      human basic fibroblast growth factor (rbFGF) in fibrin adhesive vehicle. After 10
      days of healing the maximum load*S and stress*S (S denotes correction for
      shrinkage) of ischaemic wounds were increased by 45% and 39%, respectively, after
      treatment with 20 micrograms rbFGF and by 67% and 56% after treatment with 60
      micrograms rbFGF. After 20 days only 20 micrograms rbFGF had any effect and
      increased maximum load*S by 31% and energy at maximum (load*S, stress*S) by 40%
      48%. In normal wounds 0.6-20 micrograms and 60 micrograms rbFGF decreased the
      strength parameters by 19%-34% and 49%-52%, respectively, after 10 days. After 20
      days there was no negative influence but 60 micrograms rbFGF increased the
      biomechanical properties by 15%-24%. Treatment with the fibrin adhesive vehicle
      alone decreased the biomechanical properties of ischaemic wounds after 20 days,
      and of normal wounds after both 10 and 20 days. In conclusion, rbFGF can improve
      the healing of ischaemic wounds and may be used in the treatment of ischaemic
      wounds in patients, but it can have negative effects on normal wound healing.

PMID- 9556817
TI  - The effects of L-arginine and iloprost on the viability of random skin flaps in
      rats.
AB  - The effects of an intravenous infusion of L-arginine as a physiological precursor
      of endothelium-derived relaxing factor/nitric oxide (EDRF/NO), iloprost (a stable
      prostacyclin (PGI2) analogue), and L-arginine combined with iloprost on skin
      viability were studied in 9 x 3 cm random pattern skin flaps in rats. Intravenous
      infusion of all drugs was started at the beginning of the operation and continued
      for 60 minutes. At the end of infusion period the depth of fluorescein dye
      penetration in the skin flap was assessed visually from photographic records, and
      the flap survival area was measured by the grid method at the seventh
      postoperative day. There was a significant reduction in distal necrosis of random
      skin flaps after intravenous infusion of L-arginine, iloprost, and L-arginine
      combined with iloprost (p < 0.01). Possible mechanisms that may be responsible
      for impairment of endothelium-dependent vasodilation and vasospasm in the
      microvasculature of random skin flap and their prevention with L-arginine and
      iloprost include restoration of the depleted stores of NO which in turn causes
      vasodilatation and has an antithrombotic effect.

PMID- 9556818
TI  - Metabolism in myocutaneous flaps studied by in situ microdialysis.
AB  - The aim of this investigation was to follow the metabolism of myocutaneous flaps
      using microdialysis. After subcutaneous implantation of a microdialysis catheter
      into the flap tissue, serial samples were collected and changes in composition of
      the extracellular fluid assessed. Ten women underwent reconstructions with
      transverse rectus abdominis myocutaneous (TRAM) or latissimus dorsi flaps.
      Glucose, glycerol, and lactate concentrations were measured in the flaps and
      compared with those in adipose control tissue located over the hip. A transient
      rise in glucose was observed initially in the flaps. The glycerol concentration
      also increased significantly, and remained increased for approximately 12 hours
      after the operation. The lactate concentration changed in the same direction, but
      stayed elevated in the flap tissue during the entire investigation (24 hours).
      Neither of these parameters changed to the same extent in the control tissue. In
      one of the patients a haematoma developed postoperatively in the flap. This
      incident was accompanied by a sharp decline in glucose, and marked additional
      increases in glycerol and lactate concentrations. It may well be that this
      "metabolic pattern" in flap tissue signals threatening flap ischaemia. If so,
      this new microdialysis technique may be useful as a postoperative surveillance
      tool in myocutaneous flap surgery.

PMID- 9556819
TI  - Ear reconstruction in cases of typical microtia. Personal experience based on 352
      microtic ear corrections.
AB  - The aim of this paper is to report my experience of 352 ear reconstructions to
      correct microtia with Brent's technique (n = 184) and Nagata's technique (n =
      144). The remaining 24 were atypical presentations reconstructed in a one-stage
      procedure. Brent's technique is a safe, step-by-step, four-stage reconstruction
      and Nagata's technique involves only two stages. Nagata's innovations include
      transposing the lobule of the auricle during the first stage, carving a framework
      that includes the tragus, and constructing the posterior wall of the concha
      during the second stage. Cases of typical microtia have been selected to
      illustrate the advantages and pitfalls of both techniques.

PMID- 9556820
TI  - Use of the subgaleal fascia to construct the auditory canal in microtia
      associated with aural atresia. A preliminary report.
AB  - In this paper we introduce the use of a subgaleal flap to construct the auditory
      canal in cases of microtia associated with aural atresia. The anatomy, the
      vascularisation, and the nomenclature of the different planes that constitute the
      temporal region are wellknown. The subgaleal fascia, also referred to as the
      loose areolar fascia has been until now the less surgically exploited of these
      planes. Nevertheless, it has a structure and a vascularisation that enables it to
      be dissected and used surgically. The subgaleal flap used to line the neoauditory
      canal drilled into the bone provides a vascular bed that greatly improves the
      quality of the skin graft and supports the tympanoplasty. The procedure is done
      while the ear is being raised, which constitutes the second stage of the two
      stage ear reconstruction. This new approach has been used on 22 ears. A
      preliminary analysis of the results shows that construction of the auditory canal
      has been improved.

PMID- 9556821
TI  - Speech outcome after cleft palate surgery with the Goteborg regimen including
      delayed hard palate closure.
AB  - The regimen for treatment of children with cleft lip and palate in Goteborg,
      Sweden, until 1996 included early soft palate repair at 6-8 months of age and
      delayed closure of the hard palate at about 8 years of age to improve maxillary
      growth. The aims of this report were to describe the treatment concept and to
      present speech data of 59 children treated by this method. The speech of 38
      children with unilateral and 21 with bilateral cleft lip and palate was evaluated
      perceptually from standardised tape recordings of repeated sentences and
      spontaneous speech at five ages from 3 to 16 years of age. All patients were not
      evaluated at each age level. The results showed a low prevalence of hypernasality
      after hard palate closure and pharyngeal flap surgery in only five children (8%),
      indicating a primary velopharyngeal insufficiency in less than 10% of the
      children. Only three children with bilateral clefts had glottal articulation when
      at pre-school age and no child with a unilateral cleft did. These results were
      interpreted as an indication of velopharyngeal competence (VPC) in most of the
      children. In addition, the speech problem found in these children consisted of
      retracted oral articulation of alveo-dental pressure plosives, which is almost
      always an indicator of VPC. However, we do consider that retracted oral
      articulation is a problem and to improve our results further we have decided to
      modify the technique for soft palate closure slightly and place the vomer flap
      further anteriorly to encourage narrowing of the cleft in the hard palate, and to
      close the hard palate at 3 years of age.

PMID- 9556822
TI  - Skeletal analysis of craniofacial asymmetries in plagiocephaly (unilateral
      coronal synostosis).
AB  - Why do the craniofacial bones grow asymmetrically in patients with plagiocephaly
      (unilateral coronal synostosis)? We obtained three-dimensional skeletal replicas
      of two patients with the condition and analysed the deformities of the facial
      bones. From this analysis we deduced that the asymmetric deformation of the
      facial bones in these patients was caused by a combination of three rotations:
      rotation of the calvaria toward the affected side because of premature synostosis
      of the coronal and sphenofrontal sutures; rotation of the facial bones on the
      horizontal plane toward the unaffected side caused by anterior displacement of
      the TM (temporomandibular)-joint on the affected side; and downward rotation of
      the facial bones toward the unaffected side caused by inferior displacement of
      the TM-joint on the affected side.

PMID- 9556823
TI  - Assessment of facial features with a range camera.
AB  - We describe a new method for the quantitative analysis of facial features using a
      range camera with a three-dimensional measuring program. The range camera
      consists of a video camera, a light projector, and a computer. The video camera
      captures a number of images of different light patterns projected on to the face.
      From these, a "range image" is computed. One fully illuminated intensity image of
      the face is also taken. By defining anatomical landmarks manually on the
      intensity image, three-dimensional measurements are automatically obtained from
      corresponding positions in the range image. The method is highly accurate and
      precise, and is a simple and reliable way of assessing facial features. We
      recommend that the system be adapted in clinical practice--for example, in
      diagnosing syndromes and planning plastic and reconstructive surgery.

PMID- 9556824
TI  - Melanoma of the face: the safety of narrow excision margins.
AB  - Recent studies have shown that narrower excision margins may be safe, but the
      optimal or minimum margin for melanoma is unknown. Wide margins of excision are
      possible on the trunk and limbs, but functional and cosmetic constraints often
      limit the extent of excision on the face. A collaborative study from two
      continents (Cape Town, South Africa and Northwood, England) investigated the
      outcome of different excision margins of 106 patients with stage I melanoma of
      the face. The margin of excision was measured from the records of the
      pathological specimen. Thirty patients had margins of less than 1 cm, 64 had
      margins of between 1 and 2 cm, and 12 had margins greater than 2 cm. Primary
      apposition or flap closure was possible in 85 patients. Seven patients developed
      local recurrences and these were not influenced by the excision margin. This
      study supports the contention that the primary treatment of cutaneous melanoma on
      the face should be histologically confirmed complete excision, and that this can
      be achieved with margins of excision less than 1 cm. Local recurrence is not
      related to the margin of excision or to tumour thickness.

PMID- 9556825
TI  - Treatment of non-healing ulcers of the lower extremity with free muscle flaps.
      Case reports.
AB  - The surgical management of ulcers in the lower extremity is traditionally
      conservative, and includes debridement and split thickness skin grafting. In the
      most intractable cases, however, this management is often not enough. In this
      report of three patients with non-healing ulcers of the lower extremity
      successfully treated with free muscle flaps, we advocate a more active surgical
      approach to the treatment of such conditions. This is also appropriate in
      patients for whom a microsurgical approach might not be considered because of
      advanced age, peripheral arterio-occlusive disease, or the presence of other risk
      factors.

PMID- 9556826
TI  - Macrocephaly with multiple soft tissue and visceral hamartomas ("Bannayan-Zonana"
      syndrome). Case report.
AB  - Since its first description few cases of the rare association of macrocephaly
      with multiple soft tissue and visceral hamartomas (Bannayan-Zonana syndrome) have
      been reported. In this paper we report a case of a 7 year old child in whom
      lipomas of the abdomen and right flank have been treated with liposuction. We
      could find no previous evidence that this surgical technique has been used in the
      treatment of this syndrome.

PMID- 9556827
TI  - Cholesterol crystal embolism. Case report.
AB  - A 60-year-old man presented with a cholesterol crystal embolism that gave a
      rather confusing clinical picture. An immediate multidisciplinary approach
      established the diagnosis and the rapid, dramatic skin loss that exposed vital
      structures over his thigh and lower leg was reconstructed by an ipsilateral
      inferior pedicled rectus abdominis musculocutaneous flap with a lateral oblique
      cephalad fasciocutaneal component. The case, which a plastic surgeon would rarely
      encounter, is interesting because of the diagnostic approach and the management.

PMID- 9556829
TI  - [Transplantation immunology: is the manipulation of the cytokine network
      therapeutically justified?].
AB  - Classical allograft rejection is a cellular-mediated immune response in which the
      activation of the CD4+ T helper (Th) cell plays a crucial role. After activation
      the Th cell produces a variety of cytokines which are essential for initiating
      allograft rejection. Th cells can be distinguished by their cytokine profile. Th
      1 cells produce IL-2 and IFN gamma, which are associated with rejection. Th2
      cells are characterized by the production of IL-4 and IL-10, cytokines which are
      found in models when tolerance is induced. These findings are called the "Th1/Th2
      paradigm" and lead to the following hypothesis: Th1 cells are responsible for
      allograft rejection and manipulation of the cytokine network towards a Th2 type
      cytokine pattern results in tolerance or delayed rejection. This study attempts
      to answer the question whether the Th1/Th2 paradigm is a pure association or
      corresponds to a mechanism which might be used therapeutically. Allograft
      rejection in the absence of the proinflammatory cytokines IL-2 and IFN gamma
      occurs almost unaltered. Moreover, supplying the anti-inflammatory cytokines IL-4
      and IL-10 did not result in delayed rejection. Therefore, therapeutic
      manipulation of the very complex cytokine network will most likely fail. Blocking
      cytokine-independent T cell activation might be a better concept for induction of
      allograft tolerance.

PMID- 9556828
TI  - Idiopathic isolated bilaterally symmetrical brachymetacarpia of the fifth
      metacarpal. Case report.
AB  - We report a rare case of a 32-year-old woman with idiopathic isolated bilaterally
      symmetrical brachymetacarpia of the fifth metacarpal bone, which had been present
      since the age of 14. Movement, and sensory and motor function were within normal
      limits, and she had no symptoms. No treatment was recommended. We know of no
      similar case reports.

PMID- 9556830
TI  - [Socioeconomic aspects of the changed mortality rate of coronary disease in
      Switzerland 1988-1993].
AB  - Mortality from ischemic heart disease (ICD 410-414) is changing. Remarkable
      decreases have been observed in the age groups from 35-64 years, while overall
      mortality (all age groups) has remained approximately stable. In Switzerland this
      has meant a gain of some 4700 life years in the period 1988 to 1993 in the
      working population (35-64 years). The object of this study was to assess the
      associated change in indirect costs (productivity losses) due to premature death,
      using the human capital approach. The indirect costs were CHF 519 million (CHF
      7.5 million per 100,000 population) in 1993. This represents approximately half
      of all indirect costs (and 25% of the total costs generated by the disease).
      Compared with the year 1988, a decrease in productivity losses due to premature
      death was observed amounting to CHF 46 million (-11%) in constant Swiss francs.
      Society benefits from this decrease in indirect costs, a desirable development
      hardly ever mentioned.

PMID- 9556831
TI  - [Epidemiology and care of myocardial infarct at the Fribourg Canton Hospital
      1995].
AB  - PURPOSE: This study evaluates epidemiological data in a population of patients
      admitted for acute myocardial infarction in a large Swiss community hospital. It
      focuses on the application of recent drug treatment and newer therapeutic
      techniques. METHOD: Data acquisition was based on medical records of all patients
      who were admitted to the Cantonal Hospital of Fribourg in 1995. Their one-year
      follow-up was obtained through questionnaires sent to general practitioners.
      RESULTS: During the study period: 146 myocardial infarctions were diagnosed in
      144 patients. Median age was 67.1 and 35% of patients were female. Nineteen
      percent were diabetics, 51% had hypertension and 28% had a positive family
      history for coronary artery disease. Active smokers made up 32%, 17% were past
      smokers. Myocardial infarction was anterior in 40%, inferior in 36% and non-Q
      wave myocardial infarction in 35%. Eighteen percent were subacute myocardial
      infarction. Killip class on admission were as follow: class I 65%, class II 21%,
      class III 1% and class IV 11%. Thrombolytic treatment was administered in 29% of
      patients. Vasoactive amines were used in 27% of patients and 8% were intubated
      some time during their hospital stay. At hospital discharge 81% were treated with
      Aspirin, 31% with anticoagulants, 47% with an ACE inhibitor, 38% with a beta
      blocker, 34% with nitrates and 25% with a calcium antagonist. Among this
      population, 62% had an echocardiogram, 30% a stress test and 8% a Holter
      recording. Coronary angiography was performed in 52%, which revealed 33% one
      vessel disease, 28% two-vessel disease, 25% three-vessel disease and 9% normal
      coronary arteries. Percutaneous coronary angioplasty was done in 53% of cases and
      a coronary stent implanted in 22%. Twelve percent had surgical revascularization.
      The mean hospital stay was 16.3 +/- 10.8 days, with in hospital mortality of up
      to 19.2% and a one-year mortality of 25.3%. CONCLUSION: Treatment modalities of
      patients admitted for acute myocardial infarction at the Hospital of Fribourg are
      comparable with literature data. Hypolipemic treatment has not been prescribed as
      often as recent guidelines recommend, but the use of ACE inhibitors was more
      common. As in other studies, older patients have the highest mortality. The
      absence of hospital coronarography facility did not seem to influence the
      prognosis of that population.

PMID- 9556833
TI  - [Unusual cause of cough].

PMID- 9556832
TI  - Medical treatment of migraine: from mechanisms of action to contraindications.
AB  - Management of migraine patients with or without aura must include appropriate
      medication to treat the attack and long-term preventive therapy, especially if
      the frequency of the attacks is greater than 2-4 per month. In both cases the
      choice of treatment depends on its efficacy and side effects. With regard to
      acute drug therapy, group studies do not suggest that ergot derivatives and
      sumatriptan are superior to simple analgesics and anti-inflammatory drugs,
      particularly if a prokinetic agent is added. These new substances are indicated
      for severe attacks refractory to more conventional therapy. Chronic drug abuse
      may induce drug-induced or rebound headaches. As regards long-term prophylaxis,
      group studies suggest that calcium antagonists and 5-HT-influencing drugs are
      superior concerning attacks frequency to beta-blocking agents, but involve very
      frequent side effects (weight gain and somnolence). Interesting preliminary
      results have also been reported with valproate and enalapril, which will
      confirmation by controlled studies. Finally, the choice of drug must take into
      account the patient's comorbidities (cardiovascular diseases, asthma, diabetes
      etc).

PMID- 9556834
TI  - [Annual General Assembly of the Swiss Association for Pneumonology and the Swiss
      Association for Industrial Medicine. Zurich, 26-27 March 1998].

PMID- 9556835
TI  - [Tele-immobilization of (gone) wild animals in Dutch veterinary practice. 2:
      Anesthetics used in the immobilization of wild animals].
AB  - In this article a review will be given of the groups of anaesthetics used for
      animal capture, their developmental history, mode of action and indication for
      use. A table with dosages of locally--in the Netherlands--available drugs will be
      presented for a number of animal species.

PMID- 9556838
TI  - [Cholera and swine welfare. Arbitrary reduction does not change anything of
      industrial essence].

PMID- 9556841
TI  - Duodenal mucosal permeability, bicarbonate secretion and motility. Aspects of
      regulation and integration of duodenal function in the rat. Minireview based on a
      doctoral thesis.

PMID- 9556842
TI  - Image analysis of the duodenal endocrine cells in mice with particular regard to
      optical densitometry.
AB  - The endocrine cells in the murine proximal duodenum have been investigated by
      means of immunohistochemistry and computerized image analysis. Five endocrine
      cell types were identified, namely secretin-, gastric inhibitory polypeptide
      (GIP)-, gastrin-CCK-, somatostatin- and serotonin immunoreactive cells. The
      number of endocrine cells/mm3 epithelial cells was estimated and the cell
      secretory index (CSI) for different endocrine cell types was determined.
      Furthermore, the optical density of the cellular immunoreactivity and the
      immunoreactive area in the cell were determined and an index, cell
      immunoreactivity content was estimated as the optical density multiplied by the
      immunoreactive area. It has been suggested that the use of this index might
      better reflect the cellular peptide/amine content than does the CSI. Serotonin
      immunoreactive cells were the predominant endocrine cell type, followed by
      gastrin/CCK-immunoreactive cells. The numbers of secretin-, GIP- and somatostatin
      immunoreactive cells were almost identical. All endocrine cell types were present
      both in crypts and in villi, but were, more numerous in the crypts, except for
      secretin which was more frequent in the villi.

PMID- 9556843
TI  - A survey of sleep habits and sleeping difficulties in an elderly Swedish
      population.
AB  - A random sample of 876 subjects aged 65-79 years were investigated by means of a
      questionnaire concerning sleep and related factors. Sleep problems were reported
      by 23.8% of females and 13.3% of males. Moderate or major complaints of
      maintaining sleep were reported by 43.5% of subjects, early morning awakening
      33.4% and difficulties falling asleep 31.4%. Daytime sleepiness was more common
      among males, and a relationship between daytime sleepiness and perceived poor
      sleep was found. Daytime napping was common, but not related to poor sleep. The
      prevalence of regular sleeping pill users was 7.6% for females and 3.0% for males
      and a relationship between sleep problems, sleeping pill usage and psychiatric
      symptoms was established. Among the regular sleeping pill users 39.1% had
      possible depression (PD) and 63.0% had possible anxiety disorder (PA). Among
      respondents with sleep complaints 29.8% had PD and 48.7% had PA. Sleep problems
      were also related to impaired physical health. Various medical illnesses
      contributed to sleep complaints among males, and depression affected sleep the
      most among females.

PMID- 9556844
TI  - Hyaluronan production in vitro by fetal lung fibroblasts and epithelial cells
      exposed to surfactants of N-acetylcysteine.
AB  - Fetal human lung fibroblasts and feline lung epithelial cells were exposed to
      either a surfactant or N-acetylcysteine in various concentrations for 24-48
      hours, after which the hyaluronan concentration in the culture medium was
      determined. Most of the experiments showed no stimulatory effect of either
      artificial or natural surfactant on hyaluronan synthesis. N-acetylcysteine 5-100
      mg/mL induced progressive stimulation of hyaluronan synthesis by human fetal lung
      fibroblasts, resulting in a maximum hyaluronan concentration six times that
      released by unexposed cells. A slight increase in hyaluronan synthesis was also
      observed after exposure of feline fetal lung epithelial cells to N-acetylcysteine
      50-100 micrograms/mL.

PMID- 9556845
TI  - Principles of antimicrobial therapy.
AB  - It has been 2500 years since the Chinese began applying moldy soybean curd to
      cure skin infections. Technology today has refined the benefits of antibiotic
      forming molds and bacteria and has greatly increased the number of antimicrobial
      drugs available to combat infection. Understanding the principles fundamental to
      rational therapy with these drugs will ensure the best of possible outcomes.

PMID- 9556846
TI  - Antibacterial drug therapy. Focus on new drugs.
AB  - This article will focus on the drugs for which there has been a recent or renewed
      interest in veterinary medicine. Some of these are new drugs that were recently
      introduced. Others discussed may be human-label drugs for which there has been
      recent interest in veterinary medicine because of the need for a more active drug
      or convenient regimen. For drugs such as the aminoglycosides included here,
      recent information has provided us with updated dosage guidelines.

PMID- 9556847
TI  - Antiseptics and disinfectants.
AB  - Germicidal agents used as antiseptics and disinfectants play an important role in
      the control of infection in the veterinary patient. Critical to the proper use of
      germicidal agents in or around the veterinary patient is knowledge of efficacy
      and contraindications. The key to proper use of antiseptics and disinfectants is
      using the proper germicidal agent under conditions that maximize success and
      minimize complications. Although there are a number of germicidal agents
      commercially available, effective antisepsis and disinfection can be achieved
      through use of a few effective, yet safe germicides.

PMID- 9556848
TI  - Treatment of endotoxic shock: glucocorticoids, lazaroids, nonsteroidals, others.
AB  - Review of the literature would indicate that a therapy inhibiting a single step
      in the inflammatory mediator cascade, although potentially beneficial, cannot
      serve as the "magic bullet" in endotoxic shock. Thus, combination therapy using
      drugs that target multiple steps in the mediator cascade may prove useful in the
      future. Until controlled clinical studies have been performed in veterinary
      medicine using the agents discussed in this manuscript (or others), many
      questions will remain regarding the best possible pharmacologic therapies to use
      in supplementing traditional supportive care (e.g., fluids, broad-spectrum
      antimicrobials) measures. Many of the therapies discussed in this manuscript hold
      tremendous potential, but must be administered before endotoxic shock occurs or
      early in the course of endotoxic shock to elicit a beneficial response.
      Unfortunately this is not usually possible in the clinical situation. Further,
      the possibility of eliciting a detrimental response by use of drugs at
      inappropriate dosages or too late in the course of the disease must be
      considered. In time, therapies may be grouped into those that hold promise for
      being beneficial in the patient at risk for endotoxic shock and those that are
      beneficial for treatment of established endotoxic shock. Therapies that may hold
      promise for the patient with established endotoxic shock possibly include the
      lazaroids, certain NSAIDs, pentoxifylline, and selective inhibitors of iNOS
      activity. Although still controversial, methylprednisolone and other
      glucocorticoids are probably best reserved for the patient at risk for endotoxic
      shock, or those identified very early in the course of endotoxemia and endotoxic
      shock, and should never be used in conjunction with NSAIDs. Since no one therapy
      is likely to provide the "magic bullet" for the patient in endotoxic shock,
      treatment may ultimately involve combination therapy using some of these drugs
      that target different pathways and mediators and may also include antibodies
      against endotoxin or its mediators.

PMID- 9556849
TI  - Biological response modifiers: interferons, interleukins, recombinant products,
      liposomal products.
AB  - The concept of enhancing the normal immune response against infections and
      neoplasms has been considered for decades. The administration of various natural
      and synthetic products to simulate systemic infections has largely given over to
      the idea that specific cytokines can be used effectively when administered
      systemically. Interferons, interleukins, and hematopoietic growth factors may
      offer substantial clinical benefit in chronic viral infections, and cancers such
      as osteosarcoma, melanoma, and lymphosarcoma. Erythropoietin has been shown to
      have great utility in the management of chronic renal failure. At this point in
      time, only recombinant products derived from humans are commercially available,
      and they are expensive and not licensed for use in companion animals.
      Nevertheless, these products may have significant clinical impact on several
      highly fatal disorders of dogs and cats. When administered systemically,
      cytokines perturb complex regulatory pathways, and serious side effects may
      occur. Innovative delivery methods, such as liposomes, gene therapy, and even
      oral administration may increase the therapeutic index of these molecules.
      Biological response modification, cytokine biology, and associated delivery
      systems are rapidly changing fields, and the small animal veterinarian will need
      to watch for significant advances in these areas over the next several years.

PMID- 9556850
TI  - Fluid therapy. Crystalloids and colloids.
AB  - Appropriate fluid therapy requires an understanding of fluid dynamics and
      pathologic alterations during various disease states. In addition, it requires an
      understanding of the pharmacologic differences of available fluids. Crystalloid
      fluids and colloid fluids can be used in combination to treat a variety of volume
      deficient states. Synthetic colloids are also used to treat hyponcotic states.
      Blood products are used to replace blood components and coagulation proteins.
      Frequent monitoring and reassessment are required to prevent volume overload and
      life-threatening edema.

PMID- 9556851
TI  - Drugs acting on blood and/or blood forming organs.
AB  - Pharmacologic therapy for anemia is oriented toward (1) providing components
      needed for red blood cell production (vitamin B12 and folic acid), including
      hemoglobin synthesis (iron and other minerals), and (2) stimulating bone marrow
      formation of red blood cells. Drugs used to stimulate bone marrow activity will
      be the focus of this article.

PMID- 9556852
TI  - Treatment methods for pain in the osteoarthritic patient.
AB  - Osteoarthritis is one of the most common clinical problems for which pet owners
      seek veterinary consultation. Proper management of osteoarthritis is rewarding to
      the patient, client, and veterinarian alike. The foundation for treatment of
      osteoarthritis is weight control, exercise moderation, and administration of anti
      inflammatory agents. This section of the text addresses clinically important
      mechanisms of osteoarthritis and the use of anti-inflammatory agents targeted to
      reduce pain and inflammation associated with the disease.

PMID- 9556853
TI  - Gastrointestinal drugs.
AB  - Various drugs are commonly used for the many gastrointestinal problems that are
      routinely seen in dogs and cats. Many of these drugs are briefly reviewed in this
      article. Anecdotal as well as documented findings are provided that will
      hopefully allow the clinician to use them wisely and effectively in the many
      clinical situations that arise daily. Emetics, although not used for
      gastrointestinal problems, are also reviewed because of their obvious connection
      with the gastrointestinal tract.

PMID- 9556854
TI  - Drugs used to treat reproductive disorders.
AB  - As with all aspects of medicine, it is necessary to fully understand disease
      processes before treatment modalities can be designed. Many disorders in small
      animal reproduction have not been completely evaluated, and further investigation
      is ongoing. Many reproductive hormone products are available but have limited
      clinical applicability. Other products have potential use but are not
      commercially available. A thorough diagnostic evaluation is always indicated
      before embarking on a treatment regimen.

PMID- 9556855
TI  - Anticonvulsant therapy in small animals.
AB  - Successful control of seizures with anticonvulsant drugs reflects a balance in
      achieving seizure control while minimizing undesirable drug side effects.
      Variability in the disposition of anticonvulsants and interaction among them are
      important confounders of successful therapy. This article will provide a review
      of selected anticonvulsants, focusing on drugs most likely to control seizures in
      small animals. The proper use of anticonvulsants will be discussed, with emphasis
      on differences in individual drug disposition, detection of these differences,
      and rational approaches to responding to these differences by dose modification.
      The primary target of discussion will be treatment of generalized, tonic clonic
      seizures, the most common type afflicting small animals. Opinions regarding
      anticonvulsive therapy vary among clinicians. Most of the comments and
      recommendations offered in this discussion reflect observations made from our
      therapeutic drug monitoring service and completed and ongoing clinical trials
      that focus on the use of anticonvulsants used either alone or in combination with
      phenobarbital.

PMID- 9556856
TI  - Therapeutic information on the Internet.
AB  - The internet provides a vast array of information accessible to anyone with a
      personal computer, a modem, and an internet account. It can be difficult to
      locate appropriate sites and determine their utility. This article provides a
      point-in-time sampling of the internet for therapeutic information. The URL for
      sites are provided along with a brief review of the content and its applicability
      to veterinary therapeutics.

PMID- 9556857
TI  - Production of toxic shock syndrome toxin by Staphylococcus aureus isolated from
      mastitic cow's milk and farm bulk milk.
AB  - The production of toxic shock syndrome toxin (TSST) by Staphylococcus aureus
      isolated from mastitic cow's milk and farm bulk milk was examined by a reverse
      passive latex agglutination method (RPLA). TSST was detected in 25 (58.1%) of 43
      isolates from clinical mastitic cow's milk, in 79 (76.7%) of 103 isolates from
      subclinical mastitic cow's milk, and in 95 (75.4%) of 126 isolates from farm bulk
      milk, respectively. When the quantity of TSST in the isolates was determined by
      RPLA, the titers ranged from 5 to 2560. TSST with RPLA titers of 640 to 2,560 was
      produced by 83 (30.5%) of 272 isolates tested. Almost all of the isolates showing
      RPLA titers of 640 and over produced enterotoxin C, whereas isolates showing
      titers of 5 to 320 produced enterotoxin C or both enterotoxin A and C. SDS
      polyacrylamide gel electrophoresis and isoelectric focusing with immunoblotting
      showed that the TSST from bovine isolates had same molecular size (22 kDa) and
      isoelectric point (7.2) as TSST-1 from human isolates. These findings are
      consistent with previous reports.

PMID- 9556858
TI  - Characterization of the systemic disease and ocular signs induced by experimental
      infection with Chlamydia psittaci in cats.
AB  - In addition to the commonly reported ocular signs, Chlamydia psittaci infection
      of kittens resulted in fever, lethargy, lameness and reduction in weight gain
      following ocular instillation of virulent organisms. The appearance of these
      systemic signs was late with respect to the appearance of ocular symptoms and
      occurred simultaneously with increasing levels of chlamydia-specific IgG.
      Measurement of acute phase reactants and IL-6 in plasma indicated that both
      became elevated concurrent with or slightly after the appearance of fever and
      remained elevated after the fever began to resolve. Preliminary data also
      indicated that infectious C. psittaci was present in the blood stream during this
      time period. The results of ocular instillation of three different levels of C.
      psittaci (10(3.8), 10(2.8) and 10(1.5) TCID50) indicated that the frequency of
      infection and the severity of ocular signs were diminished in the group receiving
      the lowest dose. However, the magnitude of systemic disease was similar in all
      animals which exhibited clinical signs, irrespective of the dose administered.
      The immune response to infection included elementary body (EB)-specific
      lymphocyte proliferation as well as the development of EB-specific IgG and IgM
      antibodies. The predominant antibody response was to a 45 kDa protein, the major
      outer membrane protein (MOMP), lipopolysaccharide (LPS), a 58 kDa doublet and 32
      and 16-19 kDa proteins.

PMID- 9556859
TI  - Phenotypic expression of K88 adhesion alone or simultaneously with K99 and/or F41
      adhesins in the bovine enterotoxigenic Escherichia coli strain B41.
AB  - F41-positive and F41-negative derivatives of bovine enterotoxigenic Escherichia
      coli strain B41 carrying K88 or K88 and K99 plasmids were investigated for
      stability and expression of genes for their fimbrial antigens. Either K88 plasmid
      alone or both K88 and K99 plasmids could be maintained in these strains though
      stability could depend on culture medium. K99 antigen could be detected in each
      strain bearing K99 plasmid. Clones that produced K88 antigen or clones that did
      not produce this antigen could be isolated from each strain, except from the
      strain that possessed K99 plasmid in the strain that did not possess the ability
      to produce F41 antigen. Strains possessing K88 plasmid in the strain able to
      produce F41 antigen produced clones expressing either both K88 and F41 antigens,
      (also F41 appeared strongly expressed in some clones) or clones that produced
      only F41 antigen or no antigen at all. Clones that produced only K88 antigen or
      others that did not produce this antigen could be produced from a strain bearing
      only K88 plasmid and that did not possess the ability to produce F41 antigen.
      None of these strains bearing K88 plasmid alone or additionally K99 plasmid
      produced mannose-resistant hemagglutination of horse or sheep erythrocytes at 20
      degrees C as found for K99 and F41 ETEC natural strains, respectively. These
      results suggested that the structures of pili when several genetic determinants
      were present simultaneously may not be identical to those of original strains. In
      this study, clones expressing either one, two or three adhesin bearing antigens
      could be obtained from the strain B41.

PMID- 9556860
TI  - Development of a PCR test based on a gene region associated with the
      pathogenicity of Pasteurella multocida serotype B:2, the causal agent of
      haemorrhagic septicaemia in Asia.
AB  - We have developed a PCR assay to detect Pasteurella multocida serotype B:2, the
      causal agent of Haemorrhagic Septicaemia (HS) in Asia. Nucleotide sequence
      determination of a 16S rRNA-23S rRNA PCR product unique to B:2 strains was shown
      to share amino acid sequence homology with a bacteriophage Mu protein. Primers
      designed from this sequence when tested against a panel of isolates recovered
      from a wide geographical area and representing a large range of bacterial genera
      and species, were found to specifically amplify DNA from P. multocida, serotype
      B:2. Southern hybridisation confirmed the presence of this sequence in only the
      B:2 serotype of P. multocida, suggesting an association between bacterial
      virulence and the presence of bacteriophage genes in the bacterial genome. The
      results of this study demonstrate the potential application of PCR to the
      diagnosis of HS in cattle and buffalo in Asia. Application of PCR to support
      diagnosis of HS will greatly improve accuracy, laboratory response time, and will
      facilitate rational deployment of resources for controlling this disease.

PMID- 9556861
TI  - Ochratoxin A in food and feed: occurrence, legislation and mode of action.
AB  - Ochratoxins, of which ochratoxin A (OA) is the most prevalent, are secondary
      fungal metabolites of some toxigenic species of Aspergillus and Penicillium. OA
      has been shown to be nephrotoxic, hepatotoxic, teratogenic, carcinogenic and
      immunosuppressive. The natural occurrence of OA in food and feed stuffs is
      widespread, especially in temperate areas such as Canada, Denmark, Germany,
      Sweden and the United Kingdom, and detectable amounts were even found in randomly
      collected human milk samples in Germany, Sweden and Italy. Of greatest concern in
      humans is its implicated role in an irreversible and fatal kidney disease
      referred to as Balkan Endemic Nephropathy. The mean dietary intake for humans in
      the European Union was found to be in the range of 1 to 2 ng/kg bw/day. Compared
      with the Provisional Tolerable Daily Intake (PTDI) proposed by the WHO of 16 ng
      OA/kg bw/day for humans, the average OA intake in Europe seems to be rather low.
      The main contributor to the OA intake in humans are cereals and cereal products,
      other possible contributors are coffee, beer, pork, products containing pig
      blood/plasma, pulses and spices. Only very few countries have regulations for OA
      in food and feed products. Based on the current literature, the mechanisms
      involved in the toxicity of OA indicate three major effects: (1) inhibition of
      mitochondrial respiration correlated with a depletion of ATP; (2) inhibition of
      tRNA-synthetase accompanied by a reduced protein synthesis; and (3) enhanced
      lipid peroxidation. Generation of free radicals and lipid peroxidation as an
      important mode of action of OA in vitro and in vivo is discussed in detail, as
      well as counteracting effects of dietary antioxidants.

PMID- 9556862
TI  - Effect of consumption of uncooked (RS2) and retrograded (RS3) resistant starch on
      apparent absorption of magnesium, calcium, and phosphorus in pigs.
AB  - The aim of this investigation was to study the effect of uncooked (RS2) and
      retrograded (RS3) resistant starch on the size and site of the apparent
      absorption of magnesium, calcium, and phosphorus in swine. In an experiment with
      a parallel design, three groups of six piglets each consumed for two weeks a diet
      containing either glucose, RS2 or RS3. The piglets were cannulated at the end of
      the ileum which allowed estimation of the ileal and colonic mineral absorption.
      Urine, feces, and ileal digesta were collected for measurement of magnesium,
      calcium, and phosphorus. Dietary RS2, but not RS3, versus glucose reduced (p <
      0.05) the total absorption of magnesium and calcium and the ileal absorption of
      phosphorus in the pig. Differences between species or in RS and/or mineral intake
      may explain why RS2 reduced the apparent absorption of magnesium and calcium in
      pigs in this study and raised it in rats in earlier studies.

PMID- 9556863
TI  - Iodide supplementation: 200 micrograms daily or 1,500 micrograms weekly?
AB  - 25 euthyroid volunteers were divided into two groups. Each participant of group A
      received 200 micrograms iodine in the form of diiodotyrosine per day for a period
      of eight weeks, i.e. 7 x 200 micrograms iodine/week. Each participant of group B
      received 1,500 micrograms iodide once a week for a period of eight weeks. In
      addition to the basal excretion of iodine with the collected urine, the excretion
      values in group A amounted to 67% of the applied dose in the eighth week. In
      group B, the excretion values amounted to 65% of the applied dose in the eighth
      week. Hence, no significant difference between both groups was found.

PMID- 9556864
TI  - [Eating disorders in women: a representative study].
AB  - The authors examined the prevalence rates of binge-eating behavior, binge-eating
      disorder (BED), and bulimia nervosa in a female representative random sample in
      Tyrol. The data were collected ba telephone. Of the 1,000 women, 3 (0.3%) met the
      DSM-IV diagnostic criteria for anorexia nervosa, 15 (1.5%) for bulimia nervosa,
      and 33 (3.3%) for binge-eating disorder. While bulimics were young and found in
      all weight groups, women with BED were mostly overweight or obese and found in
      all age groups. The findings show that restrained eating, dieting, and/or
      excessive exercise are risk factors for developing eating disorders.

PMID- 9556866
TI  - [Influence of lifestyle on the use of supplements in the Brandenburg nutrition
      and cancer study].
AB  - Differences in dietary habits and lifestyle factors associated with a high
      dietary intake of fruit and vegetables are discussed and used to explain the
      disparity between results of observational epidemiologic studies consistently
      showing antioxidative vitamins to exert a protective effect on chronic diseases,
      and intervention studies so far not confirming this association. Within the scope
      of the "Brandenburger Ernahrungs- und Krebsstudie", the East German contribution
      to the European Prospective Investigation into Cancer and Nutrition (EPIC), we
      examined whether study participants using supplements on a regular basis-
      minerals, vitamins, protein formulation, bran/linseed, fiber, yeast or garlic
      pills--differed from those who did not report use of supplements according to
      selected lifestyle factors and dietary intake of vitamins, minerals, fiber,
      cholesterol, and fat from food. The study sample consisted of 10,522 participants
      (4,500 men and 6,022 women) aged 35-65 years enrolled in the cohort from January
      1995 to July 1996. Regular intake of one or more supplements during the past year
      was reported by 32.6% of women and 25.5% of men. Vitamin supplements were used by
      18.8% of the women and 15.8% of the men. Figures for minerals were 14.2% for
      women and 8.6% for men, respectively. Garlic pills were taken regularly by 9.7%
      of men and 9.3% of women. Prevalence of supplement use was generally higher in
      women and was more pronounced in elderly participants. The most frequently used
      combinations were vitamin and mineral supplements, followed by a combination of
      garlic and either vitamin or mineral supplements. Increased use of supplements
      was significantly associated with higher level of education attained, regular
      engagement in sporting activities, health complaints, and dietary change during
      the previous year. No association between use of supplements and smoking status
      nor elevated alcohol consumption was observed. Body mass index above 30 was
      significantly related to increased intake of garlic pills, and in women to
      significantly increased use of vitamin and mineral supplements. For both men and
      women, age-adjusted consumption of fruit and vegetables and intake of vitamins,
      minerals, and fiber from food was higher for participants using mineral but also
      vitamin supplements compared to those who did not use these supplements. For the
      cohort of the "Brandenburger Ernahrungs- und Krebsstudie" we observed on the one
      hand that age, gender, and health-conscious lifestyle factors were related to
      supplement use. On the other hand presence of subjective health complaints was
      related to supplement use, especially for use of vitamins and minerals.
      Participants, who regularly consumed minerals and vitamins were also shown to
      have a higher intake of foods and nutrients considered to exert an antioxidative
      effect.

PMID- 9556867
TI  - Energy intake of 1 to 18 year old German children and adolescents.
AB  - In a sample of 695 healthy well-nourished German children and adolescents
      covering the total age range from 1 to 18 years, 3d weighed diet records were
      collected and measurements of body height and weight were taken. 10% non
      plausible records (reported energy intake (EI):estimated basal metabolic rate
      (BMR) < Cut off 1.06) were excluded from further analysis. The rate of non
      plausible records was low in the childhood age groups (2-6%), higher in the male
      (10%), and highest in the female adolescents (30%). Recalculation of age and sex
      specific cut offs based on assumed light physical activity levels (PAL) reduced
      the exclusion rate to 6.5% (total) and 20% (female adolescents). The reported
      energy intake of the total sample based on plausible records (n = 627, EI:BMR >
      or = 1.06) was close to the new estimations of energy requirements assuming light
      physical activity which are proposed for the revision of the current FAO/WHO
      energy requirements. The sample was of normal height and weight compared to the
      Netherlands growth references. For a definite interpretation of the low reported
      energy intake in the context of health promoting physical activity patterns of
      children and adolescents more scientific evidence should be available.

PMID- 9556865
TI  - [Comparison of gastric emptying, blood glucose, and oro-cecal transit times after
      a conventional morning meal and a Kollath breakfast].
AB  - Blood glucose kinetics and intestinal transit times were investigated in 12 adult
      volunteers aged 28 to 52 years after ingestion of a conventional morning meal
      made up of white flour rolls, butter, marmalade, and coffee with sugar as
      compared with an isocaloric Kollath-breakfast consisting of whole wheat flakes as
      a basis. For estimation of gastric emptying time the sodium-[13C]acetate breath
      test technique was used. Oro-coecal transit time and gastric emptying were
      determined by simultaneous administration of lactose-[13C]ureide and consecutive
      drawings of breath samples in intervals of 15, 30, and 60 min through 12 h. The
      13CO2-excess of the breath test samples was measured by continuous flow isotope
      ratio mass spectrometry. The postprandial rise in blood glucose following the
      ingestion of the Kollath-breakfast was lower as compared with the conventional
      morning meal, showing significant differences between the 90 min values and the
      area below the blood glucose curve. The half time of gastric emptying was not
      different between the two breakfast versions (1.7 vs. 1.6 h). The oro-coecal
      transit time averaged out at 4.2 h after the Kollath-breakfast and 5.3 h
      following the conventional morning meal. Likewise, there were no significant
      differences in the coecal retention time nor in the cumulative percentage of
      13CO2-exhalation between the two breakfast versions. Concerning the blood glucose
      kinetics the differences in the nutritional physiology between the breakfast
      based on whole wheat flakes and the conventional breakfast as claimed by Kollath
      were only detectable in outlines in our study. Gastric emptying time showed no
      differences between the two breakfast versions.

PMID- 9556868
TI  - [Out for appetite regulators].

PMID- 9556869
TI  - [Effect of nitrates on arterial blood vessels exemplified by the radial artery].
AB  - Nitrates act, in part, by causing systemic venodilation. In addition, nitrates
      lead to dilation of arterial conductance vessels. The maximal dilation capacity
      and threshold of arterial conductance vessels have so far not been examined
      thoroughly. Therefore, we tested the radial artery diameter before and after i.v.
      nitroglycerin infusions at increasing dosages (0.015, 0.05, 0.15, 0.5, and 1.5
      micrograms/kg/min), 7 min each dose in 28 patients with suspected coronary artery
      disease (mean age +/- SEM 58 +/- 2 years) using a high resolution ultrasound
      devise. The low doses of 0.05 and 0.15 microgram/kg/min, equal to dose of 2.5
      mg/12 hours and 7.5 mg/12 hours in a patient with 70 kg, led to substantial
      increases in the cross sectional luminal area of the radial artery of 14.8 +/-
      1.5% and 29.3 +/- 2.2%*, (*p < 0.05 vs baseline). The maximal increase (dilatory
      capacity) was 53.8 +/- 3.8% (mean diameter at baseline: 2.7 +/- 0.1 mm, maximal
      3.4 +/- 0.1 mm, p < 0.001). The nitrate sensitivity of the radial artery was
      estimated by calculation of the ED50, the dose that caused half-maximal dilation
      of the radial artery. The ED50 of the radial artery was 0.13 +/- 0.003
      microgram/kg/min. In conclusion, nitroglycerin leads to a dose dependent
      dilatation of peripheral conductance vessels. Low doses of 0.05 and 0.15
      microgram/kg/min lead to significant arterial dilation. The maximal dilatory
      capacity of the radial artery is 53.8 +/- 3.5%.

PMID- 9556870
TI  - [Circulating adhesion molecules (cICAM-1, lcVCAM-1) in patients with suspected
      inflammatory heart muscle disease].
AB  - Some patients with non-ischemic heart failure show inflammatory changes in the
      myocardium which are thought to be of causal or pathogenetic relevance for the
      heart failure. The intercellular adhesion molecule-1 (ICAM-1) and the vascular
      adhesion molecule-1 (VCAM-1) are membrane proteins with receptor function from
      the immunoglobulin superfamily which mediate the vascular adhesion and
      transmigration of leucocytes into the tissue and undergo increased expression in
      chronic immunological-inflammatory processes. In addition to membrane-bound
      adhesion molecules, soluble forms can be detected in serum. In the present study
      we investigated the occurrence and the significance of circulating ICAM-1 and
      VCAM-1 in 71 patients with non-ischemic heart failure (47 M/24 F, mean age: 55 +/
      11 years). METHODS: Serum concentrations of cICAM-1 and cVCAM-1 were analyzed
      using ELISA-Kits. The severity of heart failure was assessed in accordance to the
      NYHA-classification and to hemodynamic parameters (mean pulmonary pressure, left
      ventricular ejection fraction). Inflammatory heart disease was assessed
      histologically and immunohistologically (T-lymphocytes > 7.0/mm2, increased
      expression of the histocompatibility antigens of class I and II) in right
      ventricular endomyocardial biopsies. 16 healthy, age-matched patients (8 M/8 F,
      mean age: 55 +/- 6 years, mean ejection fraction 76 +/- 3%) without signs of
      inflammation in the myocardium (mean T-lymphocytes < 3.5 cells/mm2, low
      expression of HLA-class I and II) served as controls. RESULTS: The mean serum
      concentrations of circulating ICAM-1 and VCAM-1 (cICAM-1, cVCAM-1) were higher in
      patients with non-ischemic heart failure (372 +/- 107 ng/ml and 949 +/- 439
      ng/ml) than controls (264 +/- 37 and 710 +/- 164 ng/ml) (p < 0.05). The mean
      concentrations of both adhesion molecules varied as a function of the mean
      pulmonary pressure and the left ventricular ejection fracture (for cICAM-1:
      Pearson's r: 0.24 and -0.33, p < 0.05; for cVCAM-1: Pearson's r: 0.28 and -0.26,
      p < 0.05). In 38% (n = 16) of patients with elevated concentrations of cICAM-1 (>
      or = 337 ng/ml) and 41% (n = 7) of those with elevated serum levels of cVCAM-1 (>
      or = 1038 ng/ml), the myocardial biopsies showed increased lymphocytic
      infiltration between 7 and 22 T-lymphocytes/mm2 and an enhanced expression of the
      MHC antigens of class I/II as sign of an activated inflammatory process in the
      myocardium. All patients with more than 9.3 T-lymphocytes/mm2 in the myocardium
      (n = 7) had higher serum levels of cICAM-1 (447 +/- 146 ng/ml, p < 0.05 compared
      to controls) and of cVCAM-1 (1577 +/- 688 ng/ml, p < 0.001). Both adhesion
      molecules correlated significantly with the mean number of T-lymphocytes in the
      myocardium (Pearson's r: 0.31-0.37, p < 0.05). SUMMARY AND CONCLUSION: The
      present study shows that the elevated levels of cICAM-1 and cVCAM-1 are often
      found in the serum of patients with non-ischemic heart failure. These raised
      serum levels correlate with inflammatory infiltrates in the myocardial tissue and
      with the clinical and hemodynamic signs of heart failure, thus, confirming a
      connection between heart failure and inflammatory changes in the myocardium.

PMID- 9556871
TI  - [Lysis therapy in aortic dissection: by hypertrophic cardiomyopathy simulated
      myocardial infarct].
AB  - A 52-year-old patient presenting with severe thoracic pain of more than 30
      minutes duration and ST-segment elevation > 1 mV in leads V1-3 was given 100 mg
      rt-PA. With persisting thoracic pain and ST-segment elevation, coronary
      angiography was performed 90 minutes after administration of thrombolytic
      therapy. Surprisingly, angiography revealed normal coronary arteries in presence
      of marked hypertrophic cardiomyopathy. New onset of thoracic pain after four
      hours led to a chest radiograph demonstrating increased mediastinal widening and
      new pleural effusion as compared to a baseline chest film prior to rt-PA. Spiral
      computed tomography revealed overt Type B aortic dissection with an intimal flap
      and communication distal to the origin of the left subclavian artery with signs
      of a mediastinal hematoma. Immediate cardiac surgery with replacement of the
      dissected aortic segment was successfully performed. A literature review revealed
      4% of aortic dissection to present with electrocardiographic signs of acute
      myocardial infarction and 13% to have concomitant coronary artery disease;
      moreover 34 cases of aortic dissection were misdiagnosed as infarction and
      subjected to thrombolytic agents with a mortality of 64% underlining the
      importance of exclusion of dissection prior to thrombolytic therapy.

PMID- 9556872
TI  - [Progressive cardiomyopathic lentiginosis].
AB  - We report on a 30-year-old man with progressive cardiomyopathic lentiginosis.
      This syndrome is first described by Polani and Moynahan 1972. They distinguish
      between the earlier described multiple lentigines syndrome, the LEOPARD syndrome
      (L-entiginosis, E-lectrocardiographic conduction defects, O-cular hypertelorism,
      P-ulmonary stenosis, A-bnormalities of genitalia, R-etardation of growth, D
      eafness) and the progressive cardiomyopathic syndrome. The progressive
      cardiomyopathic syndrome is characterised by multiple symmetrical lentigines,
      hypertrophic obstructive cardiomyopathy and retardation of growth. All
      characteristics were present in our patient with only mild right ventricular
      hypertrophic cardiomyopathy.

PMID- 9556873
TI  - [Heart enlargement in an athlete--a diagnostic challenge].
AB  - Endurance training can result in an enlargement of the heart. These athlete's
      hearts are rarer than generally assumed. Pathological causes, resulting in an
      eccentric hypertrophy, have to be considered. We report on a 32 year old athlete
      performing approximately 10 hours of endurance training weekly. He consulted a
      physician because of a drop in performance. The eccentric left ventricular
      hypertrophy, diagnosed by means of echocardiography, was not interpreted as a
      solely physiological cardiac adaptation because the ejection fraction did not
      increase during exercise (stress-echocardiography), the left ventricular
      diastolic function (maximum E/A-ratio) was impaired at rest, and the ergometric
      performance was reduced in comparison to the heart size. The invasive diagnostics
      including myocardial biopsy demonstrate histologically a focal fibrosis as the
      result of former myocarditis. The fibrosis was possibly involved in the genesis
      of the eccentric hypertrophy based on structural dilatation through a preferably
      mesenchymal lesion. It remains open whether the long-term endurance training had
      forced the dilatation. This case demonstrates that pathological causes must be
      excluded if in athletes an enlarged heart does not concur together with a clearly
      increased ergometric performance. Stress-echocardiography and endomyocardial
      biopsy can considerably contribute to the differential diagnosis between
      physiological and pathological cardiac hypertrophy.

PMID- 9556874
TI  - [Prenatal recording of fetal heart action with magnetocardiography].
AB  - Fetal magnetocardiography (fMCG) registers the magnetic field generated by the
      fetal heart. In contrast to the fetal electrocardiogram, fECG permits non
      invasive registration of fetal heart activity and documentation of all parts of
      the PQRST-wave-forms from the second trimenon onwards. This facilitates the
      determination of cardiac time intervals and establishment of reference values for
      different stages of pregnancy. We examined 53 women in 104 recordings from the
      10th week of gestation onwards (1 to 10 recordings per individual). The fMCG (37
      magnetic channels, sampling rate 1024 Hz, bandwidth 1-200 Hz) was recorded non
      invasively over the mother's abdomen in a magnetically shielded room.
      Registration of fetal heart beats was generally successful from the 20/21th week
      of gestation onwards. In a few cases, fetal heart beats could be registered as
      early as in the 16th week. Cardiac time intervals and amplitudes of fMCG
      increased concordantly with fetal growth. Mean P wave duration increased from 31
      to 49 ms (p < 0.05), PQ interval from 95 to 107 ms (n.s.) and QRS duration from
      36 to 52 ms (p < 0.01). The mean amplitudes of the P and R waves also increased.
      FMCG, furthermore permits a prenatal diagnosis of fetal cardiac arrhythmias. We
      recorded fetal arrhythmias in 20 cases (26-38th week), including episodes of
      ventricular and supraventricular arrhythmias or atrioventricular blockings. Due
      to its high resolution, fMCG offers new information on the development of fetal
      cardiac activity which cannot be achieved by conventional methods like
      cardiotocography or dopplerultrasound. Therefore, fMCG could become a new
      diagnostic instrument for monitoring fetal wellbeing during pregnancy.

PMID- 9556875
TI  - [Evaluation of coronary artery stenosis with respiratory gated NMR angiography].
AB  - Respiratory gated MR coronary angiography is a new MR imaging technique which
      permits reconstruction of the coronary arteries from a three-dimensional data set
      obtained from contiguous parallel sections. In this study, respiratory gated MR
      angiography was applied to assess significant coronary artery stenoses (> or =
      50%). MR imaging was performed in 68 patients (50 men, 18 women) who had been
      referred to cardiac catheterization because of suspected or known coronary artery
      disease. The evaluation of coronary artery stenoses was performed in a blinded
      manner in the proximal, middle, and distal vessel segments after multiplanar
      coronary reconstruction of the MR images. Of the 680 coronary segments, 275 (40%)
      were located outside the imaging volume and were, therefore, excluded from
      further analysis. The highest sensitivity for stenosis detection was found in the
      proximal left anterior descending (LAD) and right coronary artery (RCA) with 75%
      and 71%, respectively. The overall sensitivity, however, was low with 48%. The
      overall specificity was 92%. The positive and negative predictive values were 67%
      and 85%, respectively. This study shows that significant coronary artery
      stenoses, especially in the proximal LAD and RCA, can be correctly identified
      using respiratory gated MR angiography. However, further technical improvements
      are necessary before this method may become a reliable diagnostic tool in
      clinical practice.

PMID- 9556876
TI  - [Brief analysis of heart rate variability in for determining prognosis in the
      post-myocardial infarct period: methodologically reliable alternative to long
      term ECG?].
AB  - Heart rate variability (HRV) has been established as an important risk parameter
      in patients surviving myocardial infarction. Recently, analysis of HRV
      particularly of the standard deviation of NN intervals (SDNN)--from short term
      ECG recordings has been proposed as an alternative to that from 24 hour Holter
      monitorings. The present study is the first to compare SDNN from short term
      recordings to that from 24 hour recordings with respect to risk stratification
      after myocardial infarction. In 60 patients at the time of discharge from the
      hospital, SDNN from Holter monitoring averaged 93 +/- 30 ms compared to 39 +/- 18
      determined from short term recordings. Patients with a prospectively defined
      clinical endpoint differed significantly from those with an uneventful course
      with respect to age, left ventricular ejection fraction, mean RR interval from
      Holter recording (753 +/- 153 vs 921 +/- 132 ms), mean RR from short term
      recording (783 +/- 153 vs 914 +/- 163 ms), and SDNN from the Hotler recording (71
      +/- 27 vs 97 +/- 29 ms; p < 0.001). However, patients with and without a clinical
      event could not be separated by means of SDNN measured from short term ECG
      registrations (35 +/- 22 vs 41 +/- 19 ms; p = NS). Thus, SDNN measured from short
      term ECG recordings does not seem to be useful regarding risk stratification of
      patients after myocardial infarction. Analysis of HRV should be performed using
      24 hour Holter monitoring, which provides more information and reflects circadian
      fluctuation in autonomic tone.

PMID- 9556877
TI  - [Renal urodilatin secretion is associated with diuresis and natriuresis after
      spontaneous, supraventricular tachycardia].
AB  - Patients with paroxysmal supraventricular tachycardia (SVT) may have a polyuria
      after termination of tachycardia. There is increasing evidence that the renal
      peptide urodilatin (ANP (95-126))--and not plasma ANP (ANP (99-126))--is the
      member of the natriuretic peptide family mediating natriuresis and diuresis in
      man. In patients with SVT we, therefore, analyzed the relationship between
      diuresis, natriuresis, plasma ANP, urinary urodilatin excretion and renal
      excretion of cyclic GMP, the second messenger in the ANP system. During and after
      clinical presentation with spontaneously occurring SVT, two patients with AV
      nodal and one patient with atrioventricular reentry tachycardia (heart rate 160
      to 200 bpm) were studied. Urinary urodilatin excretion was correlated to diuresis
      (r = 0.73) and natriuresis (r = 0.93); similarly urinary cyclic GMP excretion was
      related to diuresis (r = 0.80) and natriuresis (r = 0.87; p < 0.001,
      respectively). In contrast, there was no significant correlation between plasma
      ANP concentrations and diuresis (r = 0.28, n.s.) or natriuresis (r = 0.11, n.s.).
      As an explorative analysis, stepwise multiple linear regression identified
      urinary urodilatin as the most important contributor to diuresis and natriuresis
      after SVT. These data on polyuria after spontaneous SVT further support the view
      that in man urodilatin is the member of the natriuretic peptide family
      participating in kidney physiology.

PMID- 9556878
TI  - [Percutaneous transcardiac intraluminal balloon angioplasty for reopening an
      arterial thrombosis after percutaneous arterial heart catheterization in a 19
      month-old patient with tetralogy of Fallot].
AB  - Cardiac catheterization is a common cause of arterial thrombosis in children.
      Besides heparin therapy, fibrinolysis plays a major role in the therapeutic
      approaches to arterial thrombosis while surgery is rarely performed in pediatric
      patients. We report on a 19 month old patient with tetralogy of fallot, who
      developed thrombosis of the right femoral artery after a retrograde
      interventional cardiac catheterization. We performed an antegrade balloon
      angioplasty of his thrombosed femoral artery using a transvenous, transcardial
      approach via a ventricular septal defect. There were no complications. Doppler
      sonography showed no residual stenosis after 4 months.

PMID- 9556879
TI  - [Benign liver tumors].

PMID- 9556880
TI  - [Diagnosis of liver tumors--what is necessary for therapy planning?].
AB  - For the surgical treatment of liver tumors, two initial steps are necessary:
      functional operability must be proven and oncological and local inoperability
      must be ruled out. The diagnostic process consists of a series of steps,
      beginning with non-invasive procedures such as laboratory findings and
      sonography, continuing with CT, CTAP, laparoscopy in the case of hepatic
      cirrhosis, up to explorative laparotomy. The potential operability is re-checked
      after each step. Punction, MRI and scintigraphy are implemented in special cases.
      The early implementation of MRI is of particular value for the diagnosis of
      certain benign processes.

PMID- 9556881
TI  - [Diagnosis of liver tumors--when is scintigraphy of value?].
AB  - This paper illustrates the importance of utilizing radionuclide techniques to
      characterize in vivo benign liver masses. Examining the physiologic tumor
      function cholescintigraphy offers a highly specific pattern for identifying focal
      nodular hyperplasia (FNH): hypervascularisation, hepatocellular uptake and
      impaired transport of the bilirubin like tracer documented as trapping in later
      images. An hemangioma is diagnosed with high probability in case of a positive
      bloodpoolscintigraphy. But false-positive results have been reported. Therefore,
      a second unrelated examination, e.g. ultrasound, magnetic resonance imaging or
      dynamic computerized tomography is necessary to establish this diagnose in a
      sufficient certainty. If complications due to tumor growth are not expected,
      both, FNH and hemangioma need no further therapy. High sensitivity is necessary
      to establish resectability or tumor spread. Scintigraphic techniques are
      advantageous in scanning completely the whole body. On the other hand, there are
      limitations as low resolution and anatomical orientation, low specific activity
      in the tumor and artificial activity near by the tumor. To measure therapy
      effects and to detect recurrencies especially in borderline-cases positron
      emission computed tomography (PET)-technology is recommended, because PET offers
      a specific-parametric evaluation.

PMID- 9556882
TI  - [Ultrasound in diagnosis of benign and malignant liver tumors].
AB  - Sonography has a high sensitivity in diagnosing circumscript lesions in the liver
      when modern machines are used by a skilled examiner. The exact analysis of the
      sonographic imaging characteristics allows definite diagnosis in the majority of
      cases. The high prevalence of benign liver tumors has to be considered. It is
      substantiated by an evaluation of 731 own patients. The characteristics of the
      most important circumscribed liver lesions are presented and suggestions for the
      diagnostic work-up are provided.

PMID- 9556883
TI  - [Diagnostic imaging of benign and malignant liver tumors: computerized tomography
      or magnetic resonance tomography?].
AB  - A reliable preoperative detection and characterization of all liver lesions is
      necessary for the clarification of the operability of a patient. In patients, who
      are considered as good candidates for a partial liver resection, a double spiral
      CT with an oral bowel opacification and an intravenous contrast medium
      administration is recommended. In those patients, who continue to be candidates
      for partial liver resection after CT, a CT arterioportography with arterial and
      portalvenous liver enhancement should be performed as the present gold standard
      of preoperative liver diagnostics. The aim of CT arterioportography is the
      further selection of patients for liver surgery. Because of its high specificity,
      MRI is useful for the characterization of liver lesions of unknown histology. For
      the differentiation between malignant (metastases) and benign (hemangioma) liver
      lesions, MRI is the method of choice. Because of the expected technical
      developments of MRI, a short-term comparison of CT and MRI in prospective studies
      is necessary.

PMID- 9556884
TI  - [Cystic liver, an indication for liver transplantation or decompressive
      resection?].
AB  - In patients suffering from polycystic liver disease sclerosing therapy,
      decompressive hepatic resection and liver transplantation represent the main
      therapeutic options. Since 1987, 10 females with highly symptomatic polycystic
      liver disease underwent hepatic resection for decompression (five left lateral
      bisegmentectomies, one left hemihepatectomy, one right central and three
      bilateral atypical resections). Despite of a 0% lethality 3 patients developed
      complications, in two cases an abscess had to be drained and in one case a
      postoperatively increasing hepatic insufficiency required urgent liver
      transplantation. Patient's symptoms were remarkably improved in 8 cases, but only
      6 patients had a long lasting benefit over years. One patient was resected a
      second time three years after the first operation and is free of symptoms for
      another five years. 6/96 the "European Liver Transplant Registry" has listed 81
      patients after liver transplantation because of polycystic liver disease. 5-year
      survival is 78.2%. So liver transplantation offers a therapeutic alternative for
      patients severely suffering from symptoms or increasing hepatic insufficiency.

PMID- 9556885
TI  - [Non-parasitic liver cysts: laparoscopic and conventional fenestration].
AB  - From 1992 till 1997 10 patients with solitary non-parasitic liver cysts were
      treated by laparoscopically fenestration of the cysts. The size of the cysts
      varied between 8 and 16 cm (median 13.5). Conversion to laparotomy was required
      in one patient because of intraoperative bleeding. In nine patients the
      laparoscopic procedure was finished successfully. In these cases we observed no
      intraoperative complications (9/10), intraoperative blood loss amounted up to 100
      ml. Median operative time amounted to 82.5 minutes (55-155). No postoperative
      complications were observed. In two patients a cystadenoma was proven by
      postoperative histology, in both cases a liver resection was performed. During a
      median follow-up of 33 (2-43) months 2 of 7 patients treated with
      laparoscopically fenestration developed a recurrence (28%).

PMID- 9556886
TI  - [Diagnostic and therapeutic strategies in hepatocellular adenoma].
AB  - While liver hemangioma and focal nodular hyperplasia are not considered an
      indication for surgery in asymptomatic patients resection has been recommended
      for hepatocellular adenoma because of the risk of rupture and malignant
      transformation. Problems arise from differential diagnosis and the appropriate
      surgical radicality including the indication for liver transplantation. This
      retrospective analysis deals with 58 patients who underwent surgery for
      hepatocellular adenoma: resection of different extension: n = 54, liver
      transplantation n = 4. In 39.6% of the patients the tumor was an incidental
      finding. In 62.0% of the character of the lesion was unclear prior to surgery.
      Tumor rupture and bleeding occurred in 17.2%, malignant transformation in 6.9%.
      Surgical morbidity was 27.6%, mortality 5.2% with the transplant patients alive
      for 1.5, 7, 9 and 10 years. Two and five years after resection 2 patients
      developed hepatocellular carcinoma in the liver remnant. The results confirm the
      indication for surgery in hepatocellular adenoma. Diagnostic approach for solid
      liver tumors without serum increase of tumor markers should rule out FNH and
      hemangioma. In all other patients surgery should be considered whenever possible
      with the radicality of malignant disease. Liver transplantation can be discussed
      even in asymptomatic patients with multiple adenoma.

PMID- 9556887
TI  - [Focal nodular hyperplasia and liver cell adenoma: operation or observation?].
AB  - PATIENTS: In a 15-year period a total of 146 patients underwent surgery for
      benign hepatic tumors, including 54 focal nodular hyperplasias (FNH) and 23
      hepatic cell adenomas (65 hemangioma and 4 cholangioma). METHODS: The medical
      records of these patients were retrospectively analyzed with respect to tumor
      related symptoms, surgical procedures and postoperative complications. RESULTS:
      Regardless of the type of the tumor, 70% of the patients had no or only non
      specific symptoms. Most frequently, surgery was indicated due to questionable
      dignity of the lesion (adenoma 70%, FNH 41%). In hepatic cell adenomas (HCA) also
      perforation or bleeding of the tumor (17%) and severe symptoms (13%) required
      urgent operation. In two of three cases local excision of the lesion or segmental
      hepatic resection were performed, whereas extended resection procedures became
      necessary only in 20 (FNH) to 34% (HCA). The mean duration of postoperative
      intensive care treatment was significantly shorter in FNH and HCA than in other
      benign hepatic tumors (1.0 vs. 2.0 days, p < 0.01). After resection of FNH no
      fatalities or significant complications were observed. In HCA morbidity was 13%
      without related mortality (hemangioma: 3% mortality; 11% morbidity). CONCLUSION:
      The elective resection of benign hepatic tumors can be achieved with very low
      mortality and morbidity, and usually provides longterm relief of annoying
      symptoms. Whenever HCA is suspected surgery should be performed, since severe
      symptoms and spontaneous hemorrhage (30%) are common in this tumor. Also
      hepatocellular carcinoma can be excluded only by histologic work-up of the
      operative specimen. In focal nodular hyperplasia (FNH), complications are rare
      and malignant transformation does not occur even when observation is employed
      only. Resection should be restricted to symptomatic or growing tumors with
      subsequent cholestasis or to cases with uncertain diagnosis.

PMID- 9556888
TI  - [Value of colonoscopy in tumor after-care after colorectal carcinoma].
AB  - The significance of colonoscopic follow up is discussed controversially.
      Colonoscopy after resection of colorectal cancer offers the possibility of direct
      inspection and to take biopsies for the early detection of local recurrence or
      additional neoplasms. In a retrospective study we examined the benefit of regular
      colonoscopies. Between 1/1995 and 4/1996 237 colonoscopies were performed on 164
      patients after resection of colorectal cancer. The evaluation was done due to the
      stage of the primary tumor, the age of the patients, the time after operation and
      the number of previous colonoscopies. 54 adenomas were found in 35 of 164
      patients. 32% of the adenomas were diagnosed in the ascending colon or colon
      transversum. Additionally three carcinomas were found. There were two local
      recurrences and one metachronous neoplasm. Two patients were diagnosed without
      clinical symptoms and were able to undergo potential curative resection again.
      Because of the number and the localisation of diagnosed neoplasms colonoscopic
      surveillance should be performed every six months in the first two years after
      resection of colorectal cancer.

PMID- 9556889
TI  - [Detection of hL6-mRNA: new possibilities in serologic tumor diagnosis of
      colorectal carcinomas].
AB  - A study was performed to detect circulating tumor cells in patients with
      colorectal cancer using mRNA coding for the tumor associated antigen L6. The mRNA
      was determined by Reverse Transcriptase Polymerase Chain Reaction and gel
      electrophoresis. The L6 results were compared with the CEA levels. Peripheral
      blood samples were taken from 109 patients with histologically verified
      colorectal cancer. Statistics were carried out using CHI Square and Sokal and
      Rohlf's-test. Preoperatively 81.65% showed positive L6 mRNA, whereas only 58.7%
      had elevated CEA titers (p < 0.05). In all patients of the control group (n = 52)
      no L6 was detectable. Concerning our results L6 seems to be a sensitive and
      precise tool for diagnosing circulating tumor cells in colorectal cancer.

PMID- 9556890
TI  - [10 years results after repair of recurrent problem inguinal hernia with prolene
      mesh].
AB  - The repair of multiple recurrences of inguinal hernias remains a surgical
      challenge. In 38 patients with a problematic recurrent inguinal hernia we
      implanted a polypropylene mesh (Prolene) in order to reinforce the transversalis
      fascia and to repair the inguinal hernia. 20 of these were medial and 14 lateral
      hernias; 4 patients had a combination of both types. All patients were
      prospectively included into this study and were seen in median follow-up periods
      of 3 and 6 months, as well as 4 and 9 years. As early complications hematoma of
      the wound (n = 3), scrotal edema (n = 1), temporary pain at the wound site (n =
      12) and paresthesia (n = 13) occurred. Two patients (n = 2) developed a femoral
      hernia and one patient suffered from a persisting nerve injury of the
      ilioinguinal nerve. Due to the low complication and recurrency rate the tension
      free repair with polypropylene mesh is a effective method for treatment of
      problematic recurrent hernias.

PMID- 9556891
TI  - [The physician's responsibility for patient education--necessity, scope and
      modalities].

PMID- 9556892
TI  - [Diagnostic imaging in surgery].

PMID- 9556893
TI  - [Technique of laparoscopic pancreatocysto-jejunostomy].
AB  - Usually the development of a pancreatic pseudocyst in the course of pancreatitis
      is followed by surgical intervention. In case of operation an internal drainage
      is preferred to an external according to general experience. We have developed a
      simplified technique of pancreatocysto-jejunostomy without Braun- or Roux-Y
      anastomosis. Here we present our surgical strategy in the laparoscopic technique.

PMID- 9556894
TI  - [Abdomino-thoracoscopic esophagus resection--an animal experiment study].
AB  - Based on animal trials the presented study results describe a method of abdomino
      thoracoscopic oesophagectomy for the treatment of oesophageal carcinoma of the
      middle and lower third. Technical details and the advantages of the surgical
      procedure, including the avoidance of thoracotomy and the practicability of the
      thoracoscopic dissection of the oesophagus are shown. Problems exist in the
      salvage of the specimen, especially in the transcervical passage of the
      tumorbearing oesophageal part. A final evaluation of the importance of the
      minimally invasive techniques in oesophageal surgery should not be given until
      the results of clinical studies are available.

PMID- 9556895
TI  - [Is there an indication for general perioperative antibiotic prophylaxis in
      laparoscopic plastic hernia repair with implantation of alloplastic tissue?].
AB  - The implantation of alloplastic material in laparoscopically operated groin
      hernias is usually connected with perioperative prophylaxis by antibiotics. We
      doubted the usefulness of the general application in these operations. Therefore
      we made a prospective randomized study in 80 patients, beginning since April
      1996. 40 of them received perioperatively antibiotics, other 40 ones remained
      without antibiotics. These 80 patients underwent an unilateral hernioplasty and
      were without major anaesthesiologic risk. Both the groups were statistically
      comparable. As a result, no patient of both the groups suffered from an
      infectious complication. Thus, we can recommend the laparoscopic implantation of
      alloplastic meshes in "simple hernias" without perioperative antibiotic
      prophylaxis. In risk patients, antibiotics should still given further.

PMID- 9556896
TI  - [Inflammatory pseudotumor of the spleen as an incidental asymptomatic finding in
      a 44-year-old patient].
AB  - In the era of routinely used ultrasound techniques intrasplenic tumors are
      diagnosed more frequently. Usually these findings are not combined with specific
      symptoms. However, large cysts can lead to malfunctions of nearly located organs
      by displacing. Etiopathogenetic findings in our region are mainly non parasitic,
      epithelial and traumatic cysts or tumors of the spleen. We describe a large
      splenic mass of a 44 years old female patient. Pathological dignity remained
      unclear after using sonographic, radiological and clinical techniques. After
      uncomplicated total splenectomy the histopathological diagnosis revealed a
      benign, pseudoinflammatory tumor of the spleen. Inflammatory pseudotumors are a
      benign response to an unknown cause. It must be a main objective of preoperative
      diagnostics to distinguish them from malignant processes.

PMID- 9556897
TI  - [Lipoma: a rare differential gastrointestinal tumor diagnosis].
AB  - This is a case report of a female patient who during a routine follow-up after a
      gastrectomy showed a tumor of the ileo-cecal valve, which--according to all
      radiologic diagnostic procedures--was highly suspected to be a malignant tumor.
      However, the histologic diagnosis was benign lipoma. The incidence and the
      characteristics of gastrointestinal lipomas in the actual literature will be
      reviewed.

PMID- 9556898
TI  - Current aspects of adjuvant therapy of early stage ovarian cancer.
AB  - Early ovarian cancer, stages I and II, is a rare presentation of epithelial
      ovarian cancer for which adjuvant therapy may have some efficacy. More than two
      decades of studies are reviewed and conclusions offered. Additionally, important
      issues for the future therapy of this disease are presented.

PMID- 9556899
TI  - [Luteal and extraluteal receptors for hCG and LH].
AB  - The hCG/LH receptor belongs to the G-protein coupled receptor family. The gene
      for the receptor has been localised to chromosome 2p21. In addition to corpus
      luteum and testis as the classical target tissues for hCG and LH, hCG/LH
      receptors have been described in a variety of non-gonadal human tissues (e.g.
      endometrium, myometrium, fallopian tube, placenta, amnion, chorion, prostate,
      CNS, adrenal gland). Besides its modulation of endocrine functions, the hCG/LH
      receptor does probably transmit growth-factor like activities of hCG and LH in
      many of these tissues. Moreover, activating as well as inactivating mutations of
      the hCG/LH receptor gene have been described. These mutations are localised
      mainly within the transmembrane region of the receptor gene (exon 11) and are
      responsible for characteristic diseases such as familiar, male-limited precocious
      puberty as well as hypogonadism of both sexes. This review deals with the
      molecular biology of the hCG/LH receptor, its distribution within the human body,
      its functions as well as with the relevance of mutations. Finally, the
      therapeutic use of hCG in the treatment of AIDS-related Kaposis' sarcoma is
      discussed.

PMID- 9556900
TI  - [Long-term outcome of incontinence and prolapse surgery at the Heidelberg
      University Gynecologic Clinic 1980-1992].
AB  - OBJECTIVE: Long-term results after different types of operations for urinary
      stress incontinence (minimum follow-up: 18 months) as well as multiple risk
      factors for the pelvic floor were analysed in a retrospective study. STUDY
      DESIGN: Between 1980 and 1992 1283 patients underwent surgery because of urinary
      stress incontinence at the University Women's Hospital in Heidelberg. The data of
      478 patients, 430 of these after primary and 48 after recurrent surgery, were
      evaluated by questionnaires with regard to the long-term-results. RESULTS: 57% of
      patients after primary surgical therapy and 37% after recurrent surgery were
      cured for longer than 5 years or since the operation. A cure or improvement of
      the incontinence could be observed in 80% after primary and in 73% after
      recurrent surgery. Among the vaginal approaches for primary surgery the
      hysterectomy combined with colporrhaphy was most successful (60% cured or more
      than 5 years continent, 80.5% at least improved). The Burch colposuspension
      revealed even better results among the abdominal approaches (64% cured or longer
      than 5 years continent, 86% at least improved) compared to the Marshall-Marchetti
      Krantz procedure with a cure rate of 33%. For therapy of the recurrent urinary
      incontinence the abdominal Burch colposuspension showed the best results with
      cure rates of 50% and cure or improvement in 75%. Therefore the abdominal
      approach seems to be superior to vaginal techniques such as sling operations (33%
      cure rate, 67% at least improved) or only re-colporrhaphy (27% cure rate, 78% at
      least improved). CONCLUSION: For primary incontinence the hysterectomy with
      vaginal repair or the Burch colposuspension have proved to be most successful.
      For recurrent urinary incontinence the abdominal colposuspension (Burch
      procedure) seems to be superior to other approaches.

PMID- 9556901
TI  - [Therapy outcome in stage III (FIGO) ovarian carcinomas at the Leipzig University
      Gynecologic Clinic 1976-1982 and 1985-1991].
AB  - This retrospective study compares treatment results (median survival time, 5-year
      survival rate) of 153 patients diagnosed with FIGO stage III ovarian cancer
      treated between 1976 to 1982 (n = 73) and 1985 to 1991 (n = 80) respectively.
      Between 1976 to 1982, the median survival time was 12.3 months, while it
      increased up to 17.0 months during the period of 1985-1991. The 5-year survival
      rate increased from 14.0% to 28.0%. This improvement may be due to a more radical
      surgical approach and the use of platinum-based first-line chemotherapy. However,
      the difference between the two groups was not statistically significant.

PMID- 9556902
TI  - [Bioavailability of 17 beta-estradiol after transdermal administration-
      dependence on the patch system].
AB  - The objective of this study was to compare the pharmacokinetics of serum
      estradiol concentrations after application of two different transdermal estradiol
      delivery systems. Ten postmenopausal women (E2 < or = 30 pg/ml; follicle
      stimulating hormone > or = 30 mIE/ml) were prospectively randomized to a
      crossover treatment protocol separated by a 7-day wash out period. The absorption
      of estradiol was measured after application of a patch either containing 4.0 mg
      of E2 in a reservoir system or 1.8 mg of E2 in a specially designed matrix
      system. Although the increase of serum estradiol concentrations after application
      of the patches with the matrix system was slightly delayed, mean E2 levels over
      the whole observation period of 80 hours were significantly higher than those
      achieved with the reservoir system (difference of mean values: 5.1 pg/ml; p <
      0.05). This observation was most striking at the end of the observation period
      and after removal of the patches. Yet, fluctuations of hormone concentrations
      were greater with the matrix system patches, and the areas under the E2
      concentration-time curves were slightly but not significantly increased as
      compared to these of the patches with the reservoir system (3211 +/- 584 vs. 2556
      +/- 249 pg/ml x h). In conclusion, both transdermal estradiol delivery systems
      are well suited for postmenopausal hormone substitution providing stable serum
      estradiol concentrations at about 50 pg/ml, with the matrix system possibly
      increasing the life span of the patch and thus the recommended application
      period.

PMID- 9556903
TI  - [Tocolysis with a nitroglycerin patch].
AB  - We would like to present a 22 year old nullipara where preterm labor was
      successfully tocolysed using a nitro-glycerine path without sequellae side
      effects. Potential advantages and disadvantages of a transdermal nitro-glycerine
      delivery system in comparison to the commonly used intravenous fenoterol
      tocolysis is discussed.

PMID- 9556904
TI  - [Tubal pregnancy after tubal sterilization by bipolar electrocoagulation].
AB  - Sterilization belongs to the safest contraceptive methods. The most popular
      sterilization procedure is by coagulation of the fallopian tube. The failure rate
      is mainly attributed to ectopic pregnancies which can lead to the risk of life.

PMID- 9556905
TI  - [Results of the marketing research study "Acceptance of physician's office
      computer systems"].
AB  - We report on a market research study on the acceptance of computer systems in
      surgeries. 11,000 returned questionnaires of surgeons--user and nonuser--were
      analysed. We found out that most of the surgeons used their computers in a
      limited way, i.e. as a device for accounting. Concerning the level of utilisation
      there are differentials of Men-Women, West-East and Young-Old. In this study we
      also analysed the computer using behaviour of gynaecologic surgeons. As a result
      two third of all nonusers are not intending to utilise a computer in the future.

PMID- 9556906
TI  - [The Online Multimedica Service].

PMID- 9556907
TI  - Resistance to interference in human associative learning: evidence of configural
      processing.
AB  - In 4 experiments the authors used 2-stage designs to study susceptibility to
      interference in human discrimination learning. The experiments used a food
      allergy task. In Experiment 1, participants were presented with a discrimination
      in Stage 1 in which Food A predicted an allergy outcome (A-->O). In Stage 2, when
      combined with Food B, Food A predicted the absence of the allergy (B-->O, AB-->no
      O). In the test phase, Food A was found to have retained its Stage 1 association
      with the allergy despite the potentially interfering Stage 2 trials. In
      Experiment 2, a discrimination between 2 compounds (AB-->O, CD-->no O) remained
      intact despite subsequent complete reevaluation of the elements, (A-->no O, B-
      >no O, C-->O, D-->O); in Experiments 3 and 4, a discrimination between 2 pairs of
      elements (A-->O, B-->O, C-->no O, D-->no O) remained intact despite subsequent
      complete reevaluation of the AB and CD compounds, (AB-->no O, CD-->O). These
      experiments yielded evidence of remarkable resistance to interference in human
      discrimination learning. The results are at variance with the predictions of J.
      M. Pearce's (1987, 1994a) configural theory of associative learning.

PMID- 9556908
TI  - Context reinforcement degrades discriminative control: a memory approach.
AB  - This study measured effects of context reinforcement on a visual discrimination.
      Five pigeons responded to 1 key in the presence of 6 shorter wavelengths and to
      another key for 6 longer wavelengths. Psychometric functions provided measures of
      discriminative sensitivity (d') and overall stimulus control. Sensitivity and
      control were slightly but significantly better when 20% of correct choices
      yielded reinforcement than when 5% did. Reinforcement of pecks to the sample
      stimulus reduced control substantially and sensitivity slightly; noncontingent
      reinforcement during intertrial intervals also reduced control, whether such
      reinforcement was signaled or not. Accuracy was excellent during an extinction
      session, but it fell substantially when reinforcement for sample pecks was added
      during choice extinction. Simulations based on a memory model of the
      discrimination process reproduced most of the experimental findings.

PMID- 9556909
TI  - The role of temporal relationships in the transfer of conditioned inhibition.
AB  - Two experiments with rats investigated the temporal relationships under which
      conditioned inhibition will transfer to an independently conditioned excitor (CS)
      in a summation test. Experiment 1 trained 2 simultaneous inhibitors with either a
      trace or delay excitatory CS. Transfer of inhibitory behavioral control depended
      on the temporal relationship of the transfer CS to the unconditioned stimulus
      (US). Experiment 2 extended these findings by training 2 inhibitors (1
      simultaneous and 1 serial) with a single delay excitatory CS. Again, testing with
      trace and delay transfer CSs found that transfer of inhibitor control depended on
      the temporal relationship of the transfer CS to the US. In both studies, maximal
      inhibition was observed when the inhibitor signaled US omission at the same time
      as the transfer excitor signaled US presentation. The results are discussed in
      terms of the temporal coding hypothesis.

PMID- 9556910
TI  - Natural choice in nonhuman primates.
AB  - In 5 experiments, 4 monkeys and 1 ape chose between 2 food sources, each held in
      1 of the experimenter's hands while he stood in front of a cage. When choosing
      between 2 sources of the same food that differed in amount, preference for the
      larger amount decreased as the size of each good proportionately increased. A
      second finding was that subjects were indifferent between a 2-food mixture and a
      single food that was part of the mixture if the single food was the preferred
      food of the mixture, a result suggesting the less preferred food had no value.
      Experiment 6 replicated these effects in 4 additional monkeys. These effects may
      be incompatible with previous theorizing about animal choice and may reflect a
      cognitive difference between nonhuman primates and humans.

PMID- 9556911
TI  - High-level expression of bovine alpha s1-casein in milk of transgenic mice.
AB  - The bovine alpha s1-casein gene, isolated from a cosmid library, was introduced
      into the murine germline. Transgene expression occurred in all transgenic mice,
      and was confined to the lactating mammary gland. Half of the mouse lines (five
      out of ten) expressed at relatively high expression levels (> 1 mg ml-1). The
      highest levels of expression were obtained with a transgene containing 14.2 kb of
      5' flanking sequence, in two cases expression levels comparable to (10 mg ml-1)
      or well above (20 mg ml-1) alpha s1-casein levels in bovine milk were obtained.
      Transcription initiation occurred at the same site in the bovine alpha s1-casein
      gene in transgenic mouse as in the cow. A marked induction of expression occurred
      at parturition rather than at mid-pregnancy, and thus resembled the bovine rather
      than the murine developmental expression pattern. Bovine alpha s1-casein specific
      immunoblotting and RIA were developed for characterization and quantification of
      the recombinant protein. Using these assays, the properties of the recombinant
      protein could not be distinguished from those of the natural bovine protein. In
      spite of the high-level tissue-specific and correctly regulated developmental
      expression of the transgene, expression levels were integration-site dependent.
      This may indicate that not all cis-acting regulatory elements involved in bovine
      alpha s1-casein expression were included in the transgene.

PMID- 9556912
TI  - Insulin and prolactin synergize to induce translation of human serum albumin in
      the mammary gland of transgenic mice.
AB  - A dramatic uncoupling of the expression of chimaeric beta-lactoglobulin
      (BLG)/human serum albumin (HSA) gene constructs at the RNA and protein levels was
      observed in cultured mammary explants of virgin transgenic mice. Upon
      explantation, both HSA RNA and protein were expressed at high levels. However,
      when the explants were grown in hormone-free medium. HSA RNA continued to
      accumulate, whereas the synthesis of the corresponding protein was dependent on
      the presence of insulin and prolactin with a minor contribution of
      hydrocortisone. The untranslated HSA RNA was indistinguishable from its
      translatable counterpart in its mobility on agarose gels, was transported
      normally from the nucleus to the cytoplasm and was translated efficiently in
      rabbit reticulocyte lysate. In the presence of cycloheximide, HSA RNA rapidly
      disappeared suggesting a dependency on ongoing protein synthesis. Its estimated
      half-life of 5-6 h in hormone-free medium increased significantly in the presence
      of insulin, hydrocortisone and prolactin and was comparable to that of beta
      casein RNA. The uncoupling of the expression of the BLG/HSA transgenes at the RNA
      and protein levels was also confirmed by in situ hybridization and
      immunohystochemistry on sections from virgin mammary explants. HSA synthesis was
      initiated within 13 h of the addition of insulin and prolactin in explants that
      had accumulated untranslated HSA RNA and was fourfold higher than that observed
      with insulin alone. Addition of hydrocortisone contributed to an additional 20%
      in HSA synthesis. We believe this is the first demonstration of translational
      control of exogenous milk protein gene expression in the mammary gland of
      transgenic animals.

PMID- 9556913
TI  - Regulation of CAT protein by ribozyme and antisense mRNA in transgenic mice.
AB  - Transgenic mouse lines were engineered to express stably antisense mRNA or
      antisense mRNA containing catalytic ribozyme (rbz) structures complementary to
      bacterial chloramphenicol acetyltransferase (CAT) gene transcripts. One
      transgenic line expressed antisense mRNA that specifically targeted full-length
      CAT coding sequences (ACAT). Another transgenic line expressed full-length
      antisense CAT mRNA which was modified by mutagensis to include four rbz cassettes
      (rbz-ACAT) in order to compare antisense versus antisense-rbz function in vivo.
      Preliminary data were also collected from a transgenic mouse line expressing
      antisense mRNA targeting 72% of the 5' region of CAT coding sequences (5' ACAT).
      All constructs contained similar control elements in their design. Promoter
      elements were derived from the bovine alpha s1-casein gene, while the small t
      intron and 3' control sequences were derived from SV40. The ability of these
      various constructs to down-regulate CAT protein levels was compared by analysis
      of CAT protein production in lactating double-hemizygous transgenic female mice.
      Every double-hemizygous mouse analysed expressed mRNA from the alpha s1-casein
      CAT construct (Clarke et al., 1994) and equivalent levels of mRNA from one of the
      three antisense constructs. Transgenic mouse lines expressing both ACAT and CAT
      mRNA down-regulated CAT protein levels by 90% of that found in the CAT only
      transgenic population. Similarly, double-hemizygous transgenic lines expressing
      both rbz-ACAT and CAT mRNA regulated CAT protein levels by 87%. Preliminary data
      suggests that expression of mRNA from 5' ACAT/CAT double-hemizygote mice allowed
      approximately 67% down-regulation of normal CAT protein levels. We conclude that
      incorporation of multiple ribozymes within the full-length antisense CAT
      construct does not enhance the effectiveness of antisense mRNA in the down
      regulation of CAT protein production in our system.

PMID- 9556914
TI  - Differential in vivo activities of bovine growth hormone analogues.
AB  - In rodents, bovine (b) growth hormone (GH) binds only to GH receptors, while
      human (h) GH binds to both GH and PRL receptors. The phenotypic consequences of
      expression of bGH and hGH in transgenic mice are different and, in some cases,
      opposite. In the present study, site-directed in vitro mutagenesis of the bGH
      gene was used systematically to eliminate its differences from hGH at one, two,
      three or four suspected of conferring lactogenic activity: D11, H18, S57 and T60,
      respectively (corresponding to sites 12, 19, 57 and 60 of the bGH molecule). The
      resulting bGH analogues were expressed in cell lines and in transgenic mice. All
      of the seven bGH analogues produced retained their ability to bind to GH
      receptors and exhibited somatogenic activity in vitro and in vivo. However, none
      of them were able to bind to PRL receptors or to elicit detectable lactogenic
      response in vitro. Transgenic animals expressing any of the generated analogues
      were characterized by gigantism and splanchnomegaly. The effects of expression of
      each of the double, triple or quadruple mutants on the seminal vesicle weight
      resembled the effects of wild-type hGH and differed from the effects of
      expression of wild-type bGH. There were differences between the effects of the
      expression of different bGH analogues on plasma PRL levels and on the PRL
      response to pharmacological blockade of catecholamine synthesis. Plasma LH levels
      in ovariectomized females were suppressed by several of the analogues tested, an
      effect not seen in animals expressing wild-type bGH or hGH. Dopamine turnover in
      the median eminence of male mice was also altered in animals expressing different
      bGH analogues but not in those expressing wild-type bGH or hGH. In ovariectomized
      females, the effects of different bGH analogs on the turnover of dopamine and
      norepinephrine in the median eminence included changes resembling those detected
      in animals expressing hGH, as well as alterations differing from the effects of
      both bGH and hGH. The results indicate that biological actions of these bGH
      analogues cannot be characterized simply in terms of enhanced or reduced
      somatogenic or lactogenic activity and raise a possibility that different sites,
      domains or features of tri-dimensional structure of GH are involved in its
      actions on different cellular targets.

PMID- 9556915
TI  - Transgenic farm animals get off the ground. Transgenic Animals in Agriculture,
      Conference Tahoe City, California, USA. August 24-27, 1997.

PMID- 9556916
TI  - Intermediary metabolism of fast-growth tumor cells.
AB  - Tumor cells show several modifications in their metabolism in comparison with
      normal cells. In particular, tumor cells show an accelerated glycolysis and a low
      O2 dependence, which are metabolic modifications involved in the resistance of
      many tumor cell lines to radiation. Thus, a strategy to enhance the
      radiosensitivity could be the transformation of the glycolytic metabolism of
      tumor cells into an oxidative type of metabolism, i.e., to induce the ATP supply
      to depend solely on oxidative phosphorylation. Therefore, this review emphasizes
      the relevance of oxidative phosphorylation on tumor cells regarding (a) its
      contribution to ATP supply for cell duplication during the proliferative phase,
      and (b) the possible therapeutic implications of having oxidative rather than
      glycolytic tumor cells.

PMID- 9556917
TI  - Differential effects of glycosylated and non-glycosylated porcine prolactin on
      estradiol and progesterone secretion by rat granulosa cells in culture.
AB  - BACKGROUND: The objective was to better understand the interactions between
      prolactin and ovarian function. METHODS: The effects of two variants of porcine
      prolactin (pPRL) on estradiol (E2) and progesterone (P4) production by rat
      granulosa cells in culture were studied using granulosa cells obtained from large
      preovulatory follicles of pregnant mare serum gonadotropin (PMSG)-treated
      immature Sprague-Dawley rats. Cultures were performed in the absence or presence
      of hCG (0.1 IU/ml) and different concentrations of either glycosylated and non
      glycosylated (g-pPRL and ng-pPRL, respectively) pPRL. RESULTS: Dose-response
      studies showed that maximal stimulation occurred in all instances with g-pPRL at
      the dose of 10 ng/mL during the 72-h treatment period. In the case of E2, the
      maximal response was obtained in hCG-stimulated cultures, whereas the response of
      P4 was higher in cultures stimulated with g-pPRL in the absence of hCG. In a
      similar manner, the non-glycosylated form of pPRL increased, although to a lesser
      extent, the secretion of P4 only in those cultures incubated in the absence of
      hCG. In contrast to these observations, ng-pPRL was about twice as active than
      the glycosylated form on the stimulation of growth of Nb2 lymphoma cells.
      CONCLUSIONS: These data point out that glycosylation is involved in the
      differential effects of pPRL on ovarian steroidogenesis and support the role of
      carbohydrates in the structural-functional polymorphic nature of the hormone.

PMID- 9556918
TI  - Effect of policosanol on arterial blood pressure in rats. Study of the
      pharmacological interaction with nifedipine and propranolol.
AB  - BACKGROUND: Policosanol is a natural mixture of higher aliphatic primary alcohols
      isolated from sugar cane wax (Saccharum officinarum, L) with cholesterol-lowering
      effects demonstrated in experimental models and in patients with type II
      hyperlipoproteinemia. The purpose of this study is to determine the effect of
      policosanol on arterial blood pressure and its interaction with propranolol and
      nifedipine. METHODS: Single doses of policosanol (25, 50 and 200 mg/kg) orally
      administered to spontaneously hypertensive rats (SHR) did not significantly
      change arterial pressure. RESULTS: The study on pharmacological interactions
      between policosanol (200 mg/kg) and both antihypertensive agents revealed that
      pretreatment with high doses of policosanol significantly increased propranolol
      induced hypotensive effects, while the effects of nifedipine remained unchanged.
      CONCLUSIONS: Our results show that policosanol does not antagonize the
      hypotensive effect of beta-blockers but it can increase the hypotensive effect of
      beta-blockers without modifying cardiac frequency.

PMID- 9556919
TI  - Leucine catabolism in mammary tissue, liver and skeletal muscle of dam rat during
      lactation and weaning.
AB  - BACKGROUND: This study was designed to determine the effect of lactation and
      weaning on the catabolism of branched-chain amino acids (BCAA). METHODS: Rates of
      transamination and oxidation of leucine and branched chain alpha-ketoacid
      dehydrogenase (BCKD) activity were measured in homogenates of mammary gland,
      skeletal muscle and liver on day 12 of lactation and 24 h after separation of
      dams from the litter (weaning). RESULTS: Lactating dams consumed 250% more
      protein than control rats, extra protein is required for protein synthesis by the
      mammary gland, the extent to which the excess of amino acids consumed during
      lactation is utilized or oxidized by different tissues is not known. The rate of
      transamination of [1-14C] leucine by mammary tissue of lactating dams was sixfold
      higher than in virgin rats. The rate of transamination remained elevated fourfold
      in postweaning dams. Rates of transamination were three times higher in mammary
      tissue than in muscle of lactating dams. Rate of oxidation [1-14C] leucine by
      lactating mammary tissue was tenfold higher than in control tissue. CONCLUSIONS:
      The capacity of mammary tissue for transamination and oxidation of leucine
      increased greatly during lactation, suggesting that the mammary gland may play an
      important role in the catabolism of BCAA during lactation.

PMID- 9556920
TI  - Predictive value of creatine kinase (CK)-MB for diagnosis of acute myocardial
      infarction after major noncardiac surgery.
AB  - BACKGROUND: The aim of this study was to provide insight into the interpretation
      of CK-MB data after major noncardiac surgery. METHODS: Some 3,321 patients who
      underwent major non-emergent noncardiac procedures (orthopedic 31%, intrathoracic
      12%, vascular 22%, other 35%) were studied. All patients had at least two CK
      samples measured postoperatively. RESULTS: Acute myocardial infarction was
      diagnosed in 43 (1.3%) patients using study criteria including CK-MB and
      electrocardiographic data. All of the various threshold values of peak CK-MB
      values and peak CK-MB as a percentage of total CK had poor positive predictive
      values because of high false positive rates and the low rate of acute myocardial
      infarction. CONCLUSION: These data demonstrate the need for markers of myocardial
      injury with greater cardiac specificity after noncardiac surgery.

PMID- 9556921
TI  - Dynamic and randomized perturbed posturography in the follow-up of patients with
      polyneuropathy.
AB  - BACKGROUND: The purpose of the study was to investigate and follow the
      equilibrium performance of patients with chronic polyneuropathy using Dynamic
      Posturography (DP) and Randomized Perturbed Posturography (RPP). METHODS:
      Fourteen patients with chronic polyneuropathy, aged 53-83 years, were evaluated
      by clinical investigation, vibrametry, DP and RPP in a six-year follow-up. The
      patient group was compared to 14 healthy volunteers, aged 63-80 years. The DP
      comprises a sensory organization (SO) part in which the platform and visual
      surround are stable or referenced to the patient sway, with eyes open or closed.
      In a movement coordination (MC) part, the platform makes active movements. In
      RPP, the platform moves randomly in the anteroposterior direction. RESULTS:
      Comparison between the first and second study of the patient group showed
      decreased equilibrium scores under stable conditions and when vision was
      excluded. Compared with controls, the patients showed significantly lower scores
      in most of the SO test conditions except when the platform was sway referenced
      with stable surround; in the MC part, the patients showed prolonged muscular
      response latencies, and in the RPP, the patients showed increased sway areas.
      CONCLUSIONS: The results are further evidence that proprioception is probably the
      single most important sensory input for postural control in humans. Posturography
      proved to be an objective method to study and follow the equilibrium performance
      in patients with PN.

PMID- 9556922
TI  - Plasmatic levels of theophylline in asthmatic patients. Comparative evaluations
      of two different methods.
AB  - BACKGROUND: There are several criteria to choose an analytical method for drug
      monitoring. Such methods have to comply with standard values and quality control
      as well as other subjective features such as cost and the time consumed to obtain
      quantification (TCOQ). The purpose of this work was to compare two methods used
      to quantify plasmatic levels of theophylline in asthmatic patients as support to
      choose the best method. METHODS: We analyzed plasma samples from 30 asthmatic
      pediatric patients at the pediatric service of the Hospital General de Mexico,
      who were under treatment with theophylline and whose monitoring of drug levels
      was indicated. Plasma samples were analyzed by liquid chromatography (HPLC) and
      by enzyme immunoassay (EMIT), and were then compared with respect to reliability,
      as well as cost and TCOQ. RESULTS: The difference of the plasmatic levels of
      theophylline quantified by both methods was not significant (p > 0.05); both
      showed a good correlation index (r = 0.995), and both were reliable based on
      other validity parameters. However, TCOQ for HPLC was 20.0 +/- 5.5 min (mean +/-
      SD) for each sample analyzed, and 2.3 +/- 0.5 for EMIT. With respect to the cost
      of each analysis, HPLC required 2.3 +/- 0.5 USD (mean +/- SD) and EMIT 4.5 +/-
      0.3 USD. CONCLUSIONS: Analytical methods used to quantify plasmatic levels of
      theophylline based on HPLC and EMIT proved to be suitable, because they fulfilled
      the criteria and standard values regarding quality control, although
      laboratorists have to select subjectively the best method according to cost and
      TCOQ, since HPLC was less expensive, and EMIT was more rapid.

PMID- 9556923
TI  - Epidermal growth factor and gastrin in scleroderma/CREST syndrome.
AB  - BACKGROUND: The objective of this study was to determine levels of epidermal
      growth factor (EGF) and gastrin (GA) in saliva, serum, and urine in scleroderma
      (Scl) and CREST syndrome. METHODS: EGF and GA levels were measured by
      radioimmunoassay in saliva, serum and urine in 10 patients (51 years, median;
      range, 35-66 years); 9 females and 1 male with Scl, 3 females with CREST
      syndrome, and 18 age- and sex-matched controls, 17 females and 1 male free of any
      systemic inflammatory disease. RESULTS: In serum, the EGF was lower in Scl/CREST
      than controls (p = 0.02), while GA serum concentrations were higher in Scl/CREST
      (p = 0.02). In urine, EGF in Scl/CREST was slightly lower than controls (p = NS)
      and GA concentrations were higher than controls (p = 0.03). In saliva, the EGF
      levels in Scl/CREST were also slightly lower than controls (p = NS), while GA
      concentrations in both Scl/CREST and controls were not different (p = NS).
      CONCLUSIONS: Low concentrations of EGF in serum probably play a role in the
      pathogenesis of Scl/CREST. GA concentration can be increased as a consequence of
      the low levels of EGF because of the structural homology of this peptide with
      urogastrone, a GA inhibitor factor.

PMID- 9556924
TI  - Gas exchange at rest during simulated altitude in patients with chronic lung
      disease.
AB  - BACKGROUND: To characterize the gasometric and oximetric response to simulated
      altitudes of 3,100 m and sea level of patients with Chronic Obstructive Pulmonary
      Disease (COPD) and Interstitial Lung Disease (ILD) studied at 2,240 m above sea
      level. METHODS: Consecutive stable patients with COPD and ILD were studied at the
      National Institute of Respiratory Diseases, a referral center for pulmonary
      diseases in Mexico City, and a healthy control group. The patients breathed room
      air (FIO2 = 0.21), for at least 15 min, then, a hypoxic mixture (FIO2 = 0.18,
      simulating 3,100 m), and finally, a hyperoxic mixture (FIO2 = 0.28, simulating
      sea level). Arterial blood gases and oxygen saturation were measured by a pulse
      oximeter at the end of each stage. RESULTS: Twelve patients with COPD, 13
      patients with ILD and 11 healthy controls were studied. The PaCO2 and pH were
      constant in the three study stages in both groups of patients and controls. A
      slope of PaO2 vs. altitude of 9 Torr per Km was found for each of the study's
      patients, either by simple linear regression or multiple regression, which is
      identical to that previously obtained at sea level with COPD patients (Gong et
      al.). Oxygen desaturation per Km of altitude change was alinear, higher for the
      hypoxic than for the hyperoxic challenge and more severe for the most hypoxic
      patients. CONCLUSIONS: Exposure tests to simulated altitudes are safe, and orient
      the physician concerning the patient's condition at altitudes different from the
      place where the measurement is done. Alveolar ventilation remains constant
      despite hypoxia or hyperoxia during the challenges. A computer model of the lung
      reproduces many of the findings in the challenges of this study.

PMID- 9556925
TI  - Epidemiology of lymphomas in children residing in Mexico City.
AB  - BACKGROUND: The aim of this paper is to present the epidemiological
      characteristics of time, subject and place of lymphomas in children residing in
      Mexico City, Mexico (MC). METHODS: The type of study was a retrospective hospital
      survey. All records of children with lymphomas registered between 1982 and 1991
      at the main hospitals that treat children with cancer in MC were reviewed.
      Neoplasms were classified into Hodgkin's disease (HD) and non-Hodgkin's lymphomas
      (NonHL). Trend and incidence by sex, age and area of residence in MC were
      evaluated. Time of diagnosis, as well as parental occupation and educational
      level, were registered. RESULTS: A trend was only observed for HD in the total
      group (r:0.62; P = 0.05). In 1991, incidence for HD was 6.12 (rates x 10(6)) and
      3.87 for NonHL. The highest average incidence was found in children 5-9 years of
      age (5.40) for HD, and in the age groups of 1-4 and 5-9 (3.10 and 3.33,
      respectively), for NonHL. Incidence was higher among boys for both lymphoma
      categories, but the male-to-female ratio was much higher in HD. Time of
      diagnosis, incidence in terms of place of residence, and parental educational
      level and occupation also differed from one lymphoma category to the other.
      CONCLUSION: The epidemiology of HD is different from that of NonHL, both showing
      a pattern similar to that of Latin American children.

PMID- 9556926
TI  - Detection of antibodies against Trypanosoma cruzi in donors from a blood bank in
      Cuernavaca, Morelos, Mexico.
AB  - BACKGROUND: Surveys carried out in the Mexican state of Morelos indicate the
      presence of Chagas' disease. The aim of this work was to perform a pilot study to
      detect the presence of antibodies against Trypanosoma cruzi in donors from the
      Blood Bank at the Regional Hospital of Cuernavaca, Morelos. METHODS: From March
      September 1993, blood samples from 318 donors (284 men and 34 women) were
      collected. The of age range donors was from 18-45 years. Antibodies against T.
      cruzi were determined using a commercial ELISA kit. RESULTS: Fifty-four (17%)
      serum samples had antibodies against T. cruzi: 34 out of 284 men, and 20 out of
      34 women were positive (11.9 and 58.8%, respectively). Of the 128 individuals who
      donated blood more than once, 9 (7%) were positive and had previously donated
      blood from 1-4 times. Antibodies against Leishmania sp. and T. rangeli were not
      determined. CONCLUSIONS: Based on the results of this study, procedures to detect
      antibodies against T. cruzi in blood donors and the application of a
      questionnaire inquiring into risk factors for T. cruzi infection should be
      implemented.

PMID- 9556927
TI  - Anterior choroidal artery territory infarction: a case report and review.
AB  - A patient was admitted with frequent episodes of transient neurologic symptoms
      formerly described as "capsular warning syndrome". The neurologic examination
      revealed right-sided hemiplegia, diminished pinprick, decreased light touch and
      extensor right plantar response. The only documented risk factor was
      hypertriglyceridemia, and diagnosis was anterior choroidal artery territory
      infarction. This report critically reviews the clinical features of this vascular
      lesion and the MRI findings.

PMID- 9556928
TI  - Evaluation of the cryohemolysis test for hereditary spherocytosis.

PMID- 9556929
TI  - [Continuous blood pressure monitoring during stress ECG].
AB  - Using conventional methods (Riva-Rocci, oscillometric), non-invasive blood
      pressure measurements allow readings to be obtained only at discrete times, at
      intervals of at least one or two minutes. During exercise ECG recording,
      continuous blood pressure monitoring capable of detecting brief blood pressure
      changes is desirable. Our new approach is based on the known dependency of pulse
      wave velocity and blood pressure. The pulse transit time is derived from an ECG
      and a simultaneously recorded photoplethysmogram, and the blood pressure is
      computed using a linear model. In addition to the conventional ECG device, only a
      finger or ear sensor is required, so that the application of the method is quite
      easy. Results indicating dynamic blood pressure variations during an exercise ECG
      are presented.

PMID- 9556930
TI  - [Measuring breath alcohol concentration during artificial ventilation. Model
      studies of the effect of temperature and humidity on measurements by various
      sampling systems].
AB  - The present paper examined the question as to the extent to which the taking of
      gas samples for the purpose of measuring the breath alcohol concentration (BAC)
      in the expired air of patients on artificial respiration is influenced by
      temperature and humidity. For this purpose a lung model standardized at different
      alcohol concentrations was used, in which the temperature (T: 25, 30 and 35
      degrees C) and the relative humidity (RH: 50, 75 and 95%) were varied.

PMID- 9556931
TI  - Electron-microscopic examination of silicon-carbide-coated endovascular stents.
AB  - The problem of restenosis in blood vessels after balloon angioplasty could not be
      overcome by the use of metallic stents as had been anticipated. With respect to
      restenosis, clinical and experimental results now focus the attention on the risk
      that stents could initiate or potentiate vascular lesions, especially by
      inhomogenous stent expansion. Here the stent design seems to dominante depending
      on the use of well rounded structural stent-elements with appropriate surfaces
      and a material deposition which is compatible with a homogeneous stent expansion.
      With respect to hemocompatibility the surface quality of the stents is of great
      importance, too. Coating of surfaces of metallic stents for the enhancement of
      hemocompatibility might create new risks of blood vessel damages and requires a
      careful consideration of the co-expansional behaviour of the metallic substrate
      and the coating material. With these problems in mind the surface coated stent
      Tensum 3 of the Biotronik company was investigated.

PMID- 9556932
TI  - [Intrafemoral pressure measurement in different cement removal procedures during
      hip prosthesis replacement operations--experimental study with cadaver femora].
AB  - During primary hip arthroplasty an increase in intramedullary pressure (IMP) of
      up to 1000 mm Hg can be observed. As a result of this increased intrafemoral
      pressure, intramedullary constituents can pass into the venous circulation
      creating a risk of fat embolism syndrome (FES). In the present experimental study
      on 9 femora obtained from human corpses, we investigated the question as to
      whether various methods of cement removal during total hip revision arthroplasty
      are also associated with increased intramedullary pressure and a risk of FES. The
      IMP was recorded with a standardized experimental set-up during removal of cement
      from the proximal and distal regions, including removal of the cement "tip" and
      the intramedullary plug. The methods employed for this purpose included the
      osteotome and mallet, a compressed air powered chisel, and a modified
      intracorporal lithotripter. All the methods induced fluctuations in the IMP the
      highest values being recorded for the conventional method using the osteotome and
      mallet (45 mm Hg) and the lowest values for the intracorporeal lithotripter (7.5
      mm Hg). Working on the distal cement caused higher fluctuations in comparison
      with the proximal region. The study failed to reveal any increase in mean IMP,
      and all measured values were in the low pressure range (considerably below 150 mm
      Hg). While there seems to be no apparent risk of an FES developing during removal
      of cement, careless manipulation of the distal cement plug may result in higher
      intrafemoral pressures--above 150 mm Hg--thus increasing the risk of a fat
      embolism syndrome.

PMID- 9556933
TI  - [Effect of surface hardness of the femur head prosthesis on abrasive wear forces
      in pairing with polyethylene for artificial hip joints].
AB  - The problem of wear has become a major issue in total joint replacement. A
      correlation between biomaterial hardness and abrasive wear mechanisms may be
      assumed. To investigate the effect of hardness, cobalt-chromium (CoCr) femoral
      heads coated with hard amorphous-hydrogenated carbon (a-CH) were tested against
      uncoated heads under conditions of abrasive wear. The heads were paired with
      polyethylene (UHMWPE) discs in a ball-on-disc machine. The abrasive wear
      resistance of the heads increased with surface hardness, and qualitatively
      differing patterns of wear were observed on the UHMWPE surfaces, depending on the
      abrasive wear of the matching areas of the heads. Accordingly, when evaluating
      biomaterials for their suitability for use in total joint replacement, hardness
      should be considered one of the relevant factors among the material properties
      with an influence on wear.

PMID- 9556935
TI  - Enhancing management of cancer pain: contribution of the internal working model.
AB  - The purpose of this article is to organize the current knowledge regarding
      patient-related factors that can have an impact on cancer pain management by
      using the construct of the internal working model: a theoretical framework for
      integrating current knowledge and interpreting and predicting factors related to
      the management of cancer pain. These factors include patients' beliefs and
      misconceptions about cancer pain and pain treatment, meanings that patients
      ascribe to their pain, their expectations about pain relief, and communication
      between patients and clinicians about pain control. The construct of the internal
      working model predicts and explains factors related to pain control and provides
      implications for practice. It has potential utility in enhancing the quality of
      cancer pain management.

PMID- 9556934
TI  - Nurses' and pharmacists' exposure to antineoplastic drugs: findings from
      industrial hygiene scans and urine mutagenicity tests.
AB  - Data from 83 nurses and pharmacists handling antineoplastic drugs and 35
      nurse/pharmacist controls who participated in a national study of antineoplastic
      drug-handling risks were examined to investigate antineoplastic drug exposure.
      Measures of external exposure included self-completion drug logs and industrial
      hygiene scans conducted in clinical settings. Internal exposure was measured by
      urine mutagenicity tests on end-of-week 24-hour urine specimens. To control for
      potential confounders, the staff was asked to complete food and hobby diaries and
      to avoid identified mutagenic substances for 1 week before collection of 24-hour
      urine samples. On the scans of the drug handlers, 13% showed one or more spots of
      drug contamination on gloved and ungloved hands, gowns, or shoes. Of the 24-hour
      urine samples, 15% were mutagenic for Salmonella typhimurium: Rates did not
      differ significantly for drug handlers and controls. Among nurses who both
      prepared and administered antineoplastics, those with positive mutagenicity tests
      handled more doses of the drugs, used less skin protection, and had more skin
      contact with the drugs than those with negative tests. Nurses who only
      administered the drugs and had positive mutagenicity tests handled fewer doses of
      drugs than those with negative tests, but they also reported less use of
      protection and more skin contact. For both groups of nurses, skin contact with
      antineoplastics was associated with positive mutagenicity test results (p <
      0.01).

PMID- 9556936
TI  - Spouses' view during their partners' illness and treatment.
AB  - Nine spouses of people who had suffered from acute leukemia or highly malignant
      lymphoma were interviewed about their everyday life experiences throughout their
      partner's illness and treatment, and concerning their view of the professional
      care provided. The transcribed texts were subjected to phenomenological
      hermeneutic analysis. The spouses felt they were in a situation of overall severe
      crisis (i.e., experiencing feelings of distress, restrictions, and limited or
      lack of support). The analysis revealed three family types: the couple acting as
      a unit, the couple acting independently on equal terms, and the couple acting
      separately with the spouse in a subordinate position. The spouses' evaluation of
      the entire experience varied according to the family type and the spouses'
      personal resources, which influenced the availability and utilization of their
      social network as well as the support of health-care staff. Contentment was
      related to the couple acting as a unit or the couple acting independently on
      equal terms and taking control over the situation, actively asking for support
      and requiring the staff to meet their needs. Discontentment was related to
      subordination of the spouse to the partner or to health-care staff, and failure
      of the couple to obtain support between them or from others. Empowering the
      spouses may mean helping them develop their skills, providing them with
      opportunities and authority, and assisting them in gaining access to resources
      based on knowledge of the family type, the consent of the partner, and the
      spouse's freedom to make choices. This may well lead to increased efficiency and
      have positive effects for the patient, for the spouse, and for them both as a
      couple.

PMID- 9556937
TI  - Involvement of relatives in the care of the dying in different care cultures:
      involvement in the dark or in the light?
AB  - The aim of this prospective study was to increase existing knowledge about the
      involvement of relatives in care of the dying and to shed light on the relatives'
      sense of coherence. Six relatives were followed via qualitative interviews during
      the patients' final period of life and after their deaths. The patients died in
      different forms of care: surgical department, nursing home, inpatient hospice
      ward, and at home. What the relatives had in common was that they had, in
      different ways, followed the patient from the first symptoms, through different
      forms of care, up until death. Some participated very actively in the care.
      Relatives' involvement in care can be described as involvement in the light or
      involvement in the dark. Involvement in the light is based on a trusting
      relationship between the family and the staff. Involvement in the dark is based
      on insufficient interplay and collaboration, in which the relatives are not seen
      or acknowledged by the staff, but instead must grope around in the dark when they
      try to support the patient. Rapid course of illness can be a risk factor for
      involvement in the dark. It seems that the relatives' sense of coherence was an
      important factor enabling them to be involved in the light. Humanistic care can
      constitute a buffer, thereby increasing the possibilities for relatives to be
      involved in the light.

PMID- 9556938
TI  - Information needs, uncertainty, and anxiety in women who had a breast biopsy with
      benign outcome.
AB  - A retrospective, descriptive study to determine the information needs of women
      who underwent a breast biopsy with a benign outcome and to ascertain the levels
      of uncertainty and anxiety they experienced was conducted in two community health
      care sites in Winnipeg, Manitoba. A sample of 70 women completed a four-part
      survey after learning the benign breast biopsy diagnosis. The survey consisted of
      an Information Needs Questionnaire, Mishel Uncertainty in Illness Scale-
      Community Form, State-Trait Anxiety Inventory, and a Demographic Questionnaire.
      Before the study, nine information needs were identified in a focus group
      composed of women (n = 9) who had a benign breast biopsy. The nine information
      needs were arranged in 36 pairs in the Information Needs Questionnaire. Profiles
      of information needs were developed through Statistical Analysis Systems analysis
      using Thurstone's Law of Comparative Judgement--Case V. The most important
      information need of women who underwent a benign breast biopsy was knowing when
      they would learn the diagnosis. The next four information needs were categorized
      as information about the risks of developing breast cancer. Information about
      follow-up and diagnostic tests were less important than information about the
      threat of breast cancer. Women experienced heightened uncertainty and anxiety
      levels related to the benign breast biopsy experience. Profiles of information
      needs were developed for women experiencing various levels of uncertainty and
      anxiety, women of different age groups, and women who experienced with a loved
      one with breast cancer.

PMID- 9556939
TI  - Fatigue in women with breast cancer receiving radiation therapy.
AB  - Fatigue is a common complaint of individuals receiving treatment for cancer.
      There is a dearth of rigorous research investigating the clinical course and
      prognosis of fatigue over the course of radiation therapy. Seventy six patients
      with breast cancer receiving external radiation therapy were followed
      longitudinally from the onset of treatment to 6 months post-treatment. Fatigue
      significantly increased over the course of treatment, was highest at the last
      week of treatment, and returned to pretreatment levels by 3 months after
      treatment. Fatigue was not influenced by the patient's age, stage of disease,
      time since surgery, weight, and length of time since diagnosis. Fatigue was
      significantly related to symptom distress, psychologic distress, and self
      reported fatigue relief strategies. The most frequently reported self-relief
      strategies were "sit" and "sleep." Fatigue had a negative impact on the patient's
      quality of life. Impairment in quality of life was evident by the end of
      treatment, with improvement by 3 and 6 months after treatment. The second week
      through to the last week of radiation therapy are critical times to target
      interventions for the management of fatigue. The amelioration of concomitant
      symptoms is a supportive approach that might be helpful. Self-help strategies
      focusing on the cessation of activity and increasing rest were reported as
      successful by patients.

PMID- 9556940
TI  - Correlates of fatigue in survivors of breast cancer.
AB  - The purpose of this report is to describe variables associated with fatigue for
      disease-free survivors of breast cancer. On the basis of Mishel's theory of
      illness uncertainty and the antecedents of uncertainty, a cross-sectional,
      descriptive, correlational design was used to examine (a) the relationship of
      fatigue with cancer-related variables and the presence of concurrent illness and
      (b) whether fatigue and educational level explained a significant proportion of
      the variation in illness uncertainty. The Mishel Uncertainty in Illness Scale
      (MUIS) and a single fatigue item on the McCorkle & Young Symptom Distress Scale
      were used as variable measures. Data were collected from 109 women 1 to 6 years
      after treatment for Stage I to III breast cancer with no known metastasis.
      Findings showed that low to moderate fatigue persisted for women, which was
      related significantly to the presence of concurrent illness. When concurrent
      illness was taken into account, fatigue was significantly related to treatment
      with chemotherapy, irrespective of length of time since treatment, age, disease
      stage, or tamoxifen use. Finally, fatigue and education level explained a
      significant level of the variation in illness uncertainty. Nurses can identify
      and assist women who are at risk for fatigue and illness uncertainty after
      treatment for breast cancer ends.

PMID- 9556941
TI  - Development of a preparatory sensory information videotape for women receiving
      chemotherapy for breast cancer.
AB  - This study describes the development and testing of a preparatory sensory
      information (PSI) videotape for women receiving chemotherapy for breast cancer.
      In telephone interviews, 40 women described the sensations they experienced
      before, during, and after receiving chemotherapy. Sensations described by the
      women were linked with procedural and temporal elements identified by certified
      advanced practice oncology nurses to develop a script for the PSI videotape.
      Women currently receiving chemotherapy or who had completed chemotherapy within
      the last 6 months were asked to share their experiences on videotape. After
      editing, a 20-minute PSI videotape was produced. Pilot testing with a group of 20
      women demonstrated that the intervention helped to prepare them for the sensory
      experiences associated with chemotherapy and was helpful in developing
      anticipatory coping and self-care behaviors.

PMID- 9556942
TI  - Regional decrease in brain glucose metabolism in asymptomatic gene carriers of
      Machado-Joseph disease: a preliminary report.
AB  - BACKGROUND: The molecular abnormality responsible for Machado-Joseph disease
      (MJD), a neurodegenerative disorder, has recently been described. It has also
      been previously documented using positron emission tomography (PET) with [18F]-2
      fluoro-2-deoxy-D-glucose (FDG) to record the metabolic changes in the brains of
      symptomatic subjects affected with MJD. The present study evaluated these changes
      in asymptomatic MJD gene carriers, previously identified by molecular analysis.
      METHODS: PET with FDG was used to study glucose metabolism in the brains of three
      asymptomatic MJD gene carriers who were identified by molecular analysis, and in
      10 normal control subjects. RESULTS: By comparison with data obtained from normal
      control subjects, significantly decreased glucose utilization was found in the
      cerebellar hemisphere and occipital cortex of these three asymptomatic MJD gene
      carriers, suggesting preclinical disease activity. The sensitivity of diagnosis
      based on PET examination alone was 100% in this study, using significant decrease
      in glucose metabolism in the cerebellar hemisphere as a criterion. CONCLUSIONS:
      Measurement of regional brain metabolism by PET is noninvasive, and subclinical
      reduction of FDG consumption in the cerebellar hemisphere and occipital cortex is
      found to act as an objective marker of disease activity. Based on the results
      from a limited number of patients, the sensitivity of PET is sufficient to
      justify its routine use in the investigation of asymptomatic at-risk MJD
      subjects.

PMID- 9556943
TI  - High resolution computed tomography of temporal bone fracture.
AB  - BACKGROUND: High resolution computed tomography (HRCT) is highly efficient in
      demonstrating the anatomy of the temporal bone. This study evaluates its
      application to temporal bone fractures (TBF). METHODS: We collected data from 26
      cases of TBF in the past two years. All cases underwent HRCT examination. The
      clinical information was reviewed and correlated with the imaging findings.
      RESULTS: Eighty-six percent of the cases had longitudinal fractures. Axial scans
      were the most useful in identifying the fracture line. Mastoid opacification on
      routine head computed tomography (CT) was also useful in indicating possible
      TBFs. Complications of TBF, such as ossicular chain disruption, facial nerve
      damage or otorhino-liquorrhea, were identified clearly using HRCT. CONCLUSIONS:
      To minimize or prevent the sequelae of TBF, accurate radiologic evaluation is
      necessary as soon as possible after injury. HRCT of the temporal bone delineates
      the bony and soft tissue anatomy with high accuracy and we recommend it as the
      diagnostic modality of choice.

PMID- 9556944
TI  - Impact of nutritional status on the survival of lung cancer patients.
AB  - BACKGROUND: Weight loss, disease extent, performance status and sex have emerged
      as prognostic factors for lung cancer. The assessment of performance status is
      rather subjective and crude. Parameters of nutritional status were used in this
      study to represent the performance status of patients. The prevalence of protein
      calorie malnutrition in lung cancer patients and the impact of this on patient
      survival were also investigated. METHODS: Nutritional status was assessed in 150
      newly diagnosed lung cancer patients. Anthropometric and biochemical parameters
      measured were: weight/height ratio, percent of standard triceps skin-fold
      thickness, percent of standard arm muscle circumference, serum albumin,
      transferrin, creatinine height index and total lymphocyte count. Performance
      status and survival time were estimated for all patients. RESULTS: The prevalence
      of abnormality in each nutritional parameter ranged from 15 to 31%. Most of the
      patients (59%) had at least one abnormal nutritional parameter. A low profile of
      performance status was associated with lower nutritional parameters such as
      triceps skin-fold thickness, percent of standard arm muscle circumference, serum
      albumin and creatinine height index. Patients who died within six months after
      diagnosis had significantly lower values of all nutritional parameters than those
      who survived more than six months. Patients with more abnormal parameters tended
      to have poorer survival rates. CONCLUSIONS: Both anthropometric and biochemical
      nutritional parameters might be reliable indicators for the assessment of
      performance status and survival for patients with lung cancer.

PMID- 9556945
TI  - The management of patients with advanced motor neuron disease.
AB  - BACKGROUND: There is no specific treatment for motor neuron disease (MND) except
      hospice or palliative care to improve patients' quality of life and decrease
      complications. This topic is seldom discussed in Taiwan. METHODS: A retrospective
      study was conducted of patients with terminal MND who were treated and died at
      the Veterans General Hospital-Taipei from March 1986 through April 1996.
      Patients' characteristics, management, length of survival and cause of death were
      analyzed. RESULTS: Twenty-three patients (M/F, 17/6) were included. The median
      age of onset was 59 years (range, 24-69). The median interval from onset of
      symptoms to diagnosis was nine months (range, 2-36). Seventeen patients received
      mechanical ventilation for an average median of six months. Nineteen patients had
      dysphagia, 17 received long-term nasogastric tube feeding, one had gastrostomy
      and one was treated with cricopharyngeal myotomy. Pain over the neck, trunk or
      limbs was reported by 18 patients; none received narcotics. Only two patients
      received respiratory exercise training and two had a cervical collar for
      stabilization. Electronic communication aids were not available. The median
      survival from onset of symptoms was 36 months (range, 7-99). The causes of death
      included sepsis (n = 13), respiratory failure (n = 7), heart disease (n = 2) and
      MND-related cachexia (n = 1). Cardiopulmonary resuscitation was performed for 12
      patients. CONCLUSIONS: In Taiwan, management of patients with advanced MND is
      mainly hospital-based and most of the effort is focused on life-sustaining. More
      attention needs to be paid to improvement of the quality of life and dignity of
      the patient.

PMID- 9556946
TI  - The mechanism of successful colposuspension in genuine stress incontinence.
AB  - BACKGROUND: Colposuspension (Burch procedure) is one of the most effective
      surgical procedures for the cure of genuine stress incontinence in women. The aim
      of the current study was to understand the mechanism of successful
      colposuspension for treatment of this condition. METHODS: Thirty-five patients
      with primary genuine stress incontinence underwent colposuspension. Preoperative
      investigation included detailed history taking, urinalysis, pelvic floor
      relaxation assessments, one-hour pad test, Q-tip test, urodynamic study and
      perineal ultrasound urethrocystography. Follow-up results were estimated after
      one year. RESULTS: Twenty-five (71.4%) patients were completely cured; four
      (11.4%) patients showed significant improvement and six (17.1%) had recurrence of
      incontinence. The overall success rate was 82.9%. The complication rate was 20%.
      Urodynamic data revealed a significant increase in the maximal stress urethral
      closure pressure and proximal urethral transmission ratios. Perineal ultrasound
      urethrocystography and Q-tip test revealed a significant anatomic correction in
      bladder neck descent. CONCLUSIONS: This study confirmed that surgical cure of
      urinary incontinence can be achieved by restoration of the vesical neck from a
      dependent position in the pelvis to a position high behind the symphysis pubis,
      with subsequent improved pressure transmission ratios.

PMID- 9556947
TI  - Acupuncture utilization in Taiwan.
AB  - BACKGROUND: The objective of this study was to examine the prevalence of
      acupuncture utilization in Taiwan by people over 20 years of age. METHODS:
      Stratified cluster sampling was used to randomly select 20 villages and
      neighborhoods (townships), a total of 8,280 people, from northern, central,
      southern and eastern Taiwan. A structured questionnaire was used to collect
      information during home visits. A total of 5,805 questionnaires were valid for
      use in the study. RESULTS: The complete rate of home visits was 70.1%; 73.2% of
      those interviewed recognized acupuncture as one of the common therapeutic methods
      used in traditional Chinese medicine, whereas only 12.4% had received acupuncture
      treatment. Typical interviewees who had received acupuncture treatment were
      generally ethnic from southern Fukien and aged from 30-39 years; 58.3% of the 716
      interviewees had received acupuncture treatment from licensed practitioners,
      while the remainder were treated by non-licensed practitioners. CONCLUSIONS: The
      response rate to the questionnaire was high (70.1%). However, the percentage of
      people who had received acupuncture treatment was only 12.4%, while many people
      (73.2%) were familiar with it. Approximately 40% of those who received
      acupuncture treatment did so from non-licensed practitioners. This may reveal
      either a lack of awareness by the public or a lack of public protection of health
      and safety.

PMID- 9556948
TI  - Second trimester selective termination in a dizygotic twin pregnancy with
      discordancy for Down's syndrome: a case report.
AB  - A 34-year-old woman with a twin pregnancy underwent genetic amniocentesis in a
      local hospital at 18 weeks' gestation. Fetal chromosome analysis showed a boy
      without abnormal findings (46, XY) and another boy with trisomy 21 (47, XY, +21).
      Sonography showed a fetal nuchal translucency thickness for the normal twin of
      4.4 mm, and of 8.0 mm for the affected twin. The affected twin was terminated by
      ultrasonographically guided intracardiac injection of 2.5 ml (5 mEq) potassium
      chloride solution at 21 weeks' gestation. Serial ultrasound scans and
      coagulopathy tests were unremarkable. Labor was induced at 39 weeks' gestation. A
      healthy 3,080 g male infant was born vaginally with Apgar scores of 8 and 9 at
      one and five minutes, respectively. At the time of writing (one month after
      delivery), the mother and baby continue to do well. To our knowledge, this is the
      second successful case in Taiwanese literature of selective birth in twins with
      discordancy for Down's syndrome.

PMID- 9556949
TI  - Spindle cell carcinoma of the lung: a clinicopathologic presentation of three
      cases.
AB  - Three patients with spindle cell carcinoma located in the lower respiratory tract
      are presented, including cases of two monophasic and one biphasic tumor. On light
      microscopic examination, the spindle cell components of the tumors were
      histologically characterized by sheets of fusiform spindle cells that closely
      resembled a sarcoma. Keratin expression in the spindle cell components of these
      tumors, as shown by anti-cytokeratin antibody staining, demonstrated their
      epithelial nature. It is supposed that the spindle cell component displays a
      spectrum of phenotypes originating from epithelial cells with varying degrees of
      mesenchymal transformation. It is difficult to establish a diagnosis of this rare
      primary pulmonary malignancy prior to surgical intervention. A review of the
      literature allowed for a summary of the clinicopathologic characteristics of this
      tumor.

PMID- 9556950
TI  - Genitourinary tuberculosis complicated with adrenal involvement and primary
      adrenocortical insufficiency: a case report.
AB  - Genitourinary tuberculosis (TB) rarely involves the adrenal gland. A 67-year-old
      man presented with progressively hyperpigmented skin and an enlarged mass over
      both testes. Early morning plasma cortisol concentration was low and
      adrenocorticotropic hormone (ACTH) concentration was high. A rapid ACTH
      stimulation test revealed the absence of plasma cortisol response and confirmed a
      diagnosis of primary adrenocortical insufficiency. An abdomen computed tomography
      (CT) scan disclosed enlargement of the right adrenal gland and punctuate
      calcification over the left one. This is compatible with tuberculous adrenalitis.
      Currettage biopsy of the prostate demonstrated chronic granulomatous inflammation
      with Langerhan's giant cells, but without TB bacilli. Anti-TB treatment, in
      addition to glucocorticoid and mineralocorticoid replacement, was administered.
      The testicular mass decreased progressively though the results of a subsequent
      ACTH stimulation test, six months later, disclosed no significant change. A
      follow-up CT scan, one and a half years later, showed a decrease in the size of
      the right adrenal mass.

PMID- 9556951
TI  - High resistance index of Doppler ultrasound in tuberculous peritonitis presenting
      as abdominal carcinomatosis: report of two cases.
AB  - The radiologic features of tuberculous peritonitis (TB peritonitis) are seldom
      reported, and the use of color Doppler ultrasound in the diagnosis of TB
      peritonitis is even less common. Herein, we present two patients (a 29-year-old
      woman and a 56-year-old woman) who were evaluated for months of progressive
      enlargement of the abdomen, poor appetite and weight loss. In both patients,
      clinical and laboratory examinations suggested carcinoma, except a very high
      vascular resistance (resistance index 1.0 and 0.89, respectively) of the tumor
      feeding vessels detected by color Doppler ultrasound. TB peritonitis was finally
      diagnosed by exploratory laparotomy. Both patients were treated using a four-drug
      regimen of isoniazid, rifampicin, ethambutol hydrochloride and pyrazinamide for
      nine months and were clinically cured. In conclusion, if color Doppler ultrasound
      reveals normal ovaries, ascites containing thin, delicate incomplete or complete
      septa, and only a few high-resistance tumor feeding vessels in the abdominal
      cavity (resistance index > or = 0.80), TB peritonitis should be considered.

PMID- 9556952
TI  - [Skin manifestations in diabetes can be diagnosed early. Perforated dermatoses:
      only scratching artefacts?].

PMID- 9556953
TI  - [Sleep deprivation in depression].

PMID- 9556954
TI  - [Antidepressive therapy--safety in steering in spite of it].

PMID- 9556955
TI  - [Candida and the gastrointestinal tract. A medical-research evaluation].
AB  - In immunocompetent persons, Candida species are members of the normal flora of
      the gastrointestinal tract. Budding yeasts, in particular Candida albicans, can,
      however, in patients with a corresponding disposition, spread topically and
      systemically, that is, they may become pathogenic. In hematological/oncological
      patients with severe immunodeficiency, for example, the mycelium may infiltrate
      the muscularis mucosae, with involvement also of the vascular system. The
      relationships between recurrent diarrhea and Candida are still discussed
      controversial; various data do, however, suggest that massive colonization with
      Candida might well represent a(n additional) diarrhea-provoking factor. Similar
      considerations may also be assumed to apply to diarrhea induced by antibiotic
      therapy. For immunocompetent persons, guidelines exist for the yeast cell count
      in the stools. The interpretation of quantitative findings must, however, always
      be made on an individual basis and against the background of clinical symptoms
      and/or any particular predisposition of the patient. Reliable treatment of
      superficial candidasis can be achieved with oral polyene antifungal antibiotics
      (nystatin, amphotericin B).

PMID- 9556956
TI  - [Dysphagia after antibiotics? Radiologic examination shows no useful finding].

PMID- 9556957
TI  - [Acne in childhood].

PMID- 9556958
TI  - Anesthesia control using midlatency auditory evoked potentials.
AB  - This paper shows the development of a system to control inhalation anesthetic
      concentration delivered to a patient based upon that patient's midlatency
      auditory evoked potentials (MLAEP's). It was developed and tested in dogs by
      determining response to the supramaximal stimulus of tail clamping. Prior to tail
      clamp, the MLAEP was recorded along with inhalational anesthetic concentration
      and classified as responders or nonresponders as determined by tail clamping.
      This was performed at a number of different anesthetic levels to obtain a data
      training set. The MLAEP's were compacted by means of discrete time wavelet
      transform (DTWT), and together with anesthetic concentration value, a stepwise
      discriminant analysis (SDA) was performed to determine those features which could
      separate responders from nonresponders. It was determined that only three
      features were necessary for this recognition. These features were then used to
      train a four-layer artificial neural network (ANN) to separate the responders
      from nonresponders. The network was tested using a separate set of data,
      resulting in a 93% recognition rate in the anesthetic transition zone between
      responders and nonresponders, and 100% recognition rate outside this zone. The
      anesthetic controller used this ANN combined with fuzzy logic and rule-based
      control. A set of ten animal experiments were performed to test the robustness of
      this controller. Acceptable clinical performance was obtained, showing the
      feasibility of this approach.

PMID- 9556959
TI  - Filter matrix estimation in automated DNA sequencing.
AB  - In four-color fluourescence-based automated DNA sequencing, a 4 x 4 filter matrix
      parameterizes the relationship between the dye-intensity signals of interest and
      the data collected by an optical imaging system. The filter matrix is important
      because the estimated DNA sequence is based on the dye intensities that can only
      be recovered via inversion of the matrix. In this paper, we present a calibration
      method for the estimation of the columns of this matrix, using data generated
      through a special experiment in which DNA samples are labeled with only one
      fluorescent dye at a time. Simulations and applications of the method to real
      data are provided, with promising results.

PMID- 9556960
TI  - Systematic method for determining intravenous drug treatment strategies aiding
      the humoral immune response.
AB  - This paper delineates a systematic method for determining "optimal" intravenous
      drug delivery strategies for patients having illnesses that primarily evoke a
      humoral immune response and are treatable by antibiotics. The method derives from
      a nonlinear, distributed predator-prey model that captures the dominant antigen
      and antibody interaction. This model is developed from relevant physiology, past
      predator-prey-type modeling work, available data, and pertinent parameter
      identification. Embedding this predator-prey model into a larger class of
      uncertain systems, by a finite dimensional approximation and a transformation to
      a linear fractional representation, enables the application of robust control
      based on linear matrix inequality optimization techniques. The optimization
      problem is solved by minimizing an upper bound on a measure of the total drug
      delivered subject to patient recovery (stability to healthy equilibrium state).
      Specifically, the paper addresses the treatment of Haemophilus influenzae through
      modeling, controller development, and simulations of infected adult patients
      subjected to typical and proposed intravenous antibiotic treatments. Through
      simulations the proposed intravenous drug strategy shortens patient recovery
      time, lowers peak drug concentrations and decreases the total drug administered
      when compared to standard antibiotic strategies.

PMID- 9556961
TI  - A critical analysis of linear inverse solutions to the neuroelectromagnetic
      inverse problem.
AB  - This paper explores the possibilities of using linear inverse solutions to
      reconstruct arbitrary current distributions within the human brain. We formally
      prove that due to the underdetermined character of the problem, the only class of
      measurable current distributions that can be totally retrieved are those of
      minimal norm. The reconstruction of smooth or averaged versions of the currents
      is also explored. A solution that explicitly attempts to reconstruct averages of
      the current is proposed and compared with the minimum norm and the minimum
      Laplacian solution. In contrast to the majority of previous analysis carried out
      in the field, in the comparisons, we avoid the use of measures designed for the
      case of dipolar sources. To allow for the evaluation of distributed solutions in
      the case of arbitrary current distributions we use the concept of resolution
      kernels. Two summarizing measures, source identifiability and source visibility,
      are proposed and applied to the comparison. From this study can be concluded: 1)
      linear inverse solutions are unable to produce adequate estimates of arbitrary
      current distributions at many brain sites and 2) averages or smooth solutions are
      better than the minimum norm solution estimating the position of single point
      sources. However, they systematically underestimate their amplitude or strength
      especially for the deeper brain areas. Based on these result, it appears unlikely
      that a three-dimensional (3-D) tomography of the brain electromagnetic activity
      can be based on linear reconstruction methods without the use of a significant
      amount of a priori information.

PMID- 9556962
TI  - Bipolar stimulation of a three-dimensional bidomain incorporating rotational
      anisotropy.
AB  - A bidomain model of cardiac tissue was used to examine the effect of transmural
      fiber rotation during bipolar stimulation in three-dimensional (3-D) myocardium.
      A 3-D tissue block with unequal anisotropy and two types of fiber rotation (none
      and moderate) was stimulated along and across fibers via bipolar electrodes on
      the epicardial surface, and the resulting steady-state interstitial (phi e) and
      transmembrane (Vm) potentials were computed. Results demonstrate that the
      presence of rotated fibers does not change the amount of tissue polarized by the
      point surface stimuli, but does cause changes in the orientation of phi e and Vm
      in the depth of the tissue, away from the epicardium. Further analysis revealed a
      relationship between the Laplacian of phi e, regions of virtual electrodes, and
      fiber orientation that was dependent upon adequacy of spatial sampling and the
      interstitial anisotropy. These findings help to understand the role of fiber
      architecture during extracellular stimulation of cardiac muscle.

PMID- 9556963
TI  - An externally powered, multichannel, implantable stimulator-telemeter for control
      of paralyzed muscle.
AB  - An implantable integrated stimulator and telemetry system has been developed. The
      system is capable of fulfilling the stimulus and telemetry needs of advanced
      functional neuromuscular stimulation (FNS) applications requiring multiple
      channels of stimulation and multiple channels of sensor or biopotential sensing.
      This system provides a command control structure, an inductive radio frequency
      link providing power to the implant device as well as two-way transcutaneous
      communication, an ASIC for decoding the command and for providing functional
      control within the implant, and modular circuitry providing the application
      specific implant functions. Biocompatible hermetic packaging, lead systems, and
      in-line connectors suitable for long-term implantation, provide encapsulation for
      the circuitry and access to the electrodes and sensors used in the application.
      The first implant configuration realized from this modular system is targeted for
      clinical implementation in persons with tetraplegia at the C6 level for
      restoration of hand function, using wrist position as the command control source.
      The implant device realized has ten channels of stimulation and telemetry used to
      control and sense a joint angle transducer implanted in the radio-carpal joint of
      the wrist. A prototype device has been fabricated and is undergoing testing in an
      animal.

PMID- 9556964
TI  - Measurement of friction on straight catheters in in vitro brain and phantom
      material.
AB  - As part of our studies on the magnetic stereotaxis system (MSS), a means of
      delivering therapies to the bulk brain, we have measured the frictional forces on
      a thin, straight tube used to simulate a catheter. Experiments were done with a
      spring-loaded, stainless steel tube of 1.9-mm diameter which was passed through
      5.5 cm of gelatin phantom or, alternatively, through in vitro calf brain. The
      dynamic response of the tube to sudden displacement of the outer end of the
      spring yields estimates of the tube's friction per unit length. Twenty-three runs
      in the two media were analyzed for the static and dynamic frictional forces
      exhibited. In these series the static frictional forces were found to be (0.0132
      +/- 0.0012) N cm-1 [(1.32 +/- 0.12) g cm-1] of length in the gelatin phantom and
      (0.0079 +/- 0.0008) N cm-1 [(0.79 +/- 0.08) g cm-1] of length in brain. The
      kinetic friction coefficient, b, was found to be (8.4 +/- 2.1) N s m-1/cm length
      of catheter in brain and (16.3 +/- 7.6) N s m-1/cm length of catheter in the
      phantom material. Based on these figures, the MSS will be capable of moving
      straight catheters of similar friction that are 20-cm long at rates of
      displacement of 0.02 to 0.05 cm s-1 in the white and grey matter of the brain.
      Future studies will evaluate the forces arising from curved paths. Unanswered
      questions remain as to the mechanical difference between in vivo and in vitro
      brain, between animal and human brain, and the involvement of sulci in practical
      paths of motion.

PMID- 9556965
TI  - A Kalman filter approach to track fast impedance changes in electrical impedance
      tomography.
AB  - In electrical impedance tomography (EIT), an estimate for the cross-sectional
      impedance distribution is obtained from the body by using current and voltage
      measurements made from the boundary. All well-known reconstruction algorithms use
      a full set of independent current patterns for each reconstruction. In some
      applications, the impedance changes may be so fast that information on the time
      evolution of the impedance distribution is either lost or severely blurred. In
      this paper, we propose an algorithm for EIT reconstruction that is able to track
      fast changes in the impedance distribution. The method is based on the
      formulation of EIT as a state-estimation problem and the recursive estimation of
      the state with the aid of the Kalman filter. The performance of the proposed
      method is evaluated with a simulation of human thorax in a situation in which the
      impedances of the ventricles change rapidly. We show that with optimal current
      patterns and proper parameterization, the proposed approach yields significant
      enhancement of the temporal resolution over the conventional reconstruction
      strategy.

PMID- 9556966
TI  - System for quantitative three-dimensional echocardiography of the left ventricle
      based on a magnetic-field position and orientation sensing system.
AB  - Accurate measurement of left-ventricular (LV) volume and function are important
      to monitor disease progression and assess prognosis in patients with heart
      disease. Existing methods of three-dimensional (3-D) imaging of the heart using
      ultrasound have shown the potential of this modality, but each suffers from
      inherent restrictions which limit its applicability to the full range of clinical
      situations. We have developed a technique for image acquisition using a magnetic
      field system to track the 3-D echocardiographic imaging planes and 3-D image
      analysis software including the piecewise smooth subdivision method for surface
      reconstruction. The technique offers several advantages over existing methods of
      3-D echocardiography. The results of validation using in vitro LV's show that the
      technique allows accurate measurement of LV volume and anatomically accurate 3-D
      reconstruction of LV shape and is, therefore, suitable for analysis of regional
      as well as global function.

PMID- 9556967
TI  - Successive order scattering transport approximation for laser light propagation
      in whole blood medium.
AB  - An analytical solution method of the radiative transport equation, describing
      light scattering distribution in whole blood, is derived by applying successive
      order scattering approximation and transport approximation. By separating
      coherent components of scattered fluxes, the transport equation can be
      represented in terms of each order scattering flux, and the equations for each
      order scattering flux have a simplified integration term of scattering
      contribution that usually makes the solution complicated or even impossible.
      Also, actual phase function can be used for calculation of angular dependent
      scattering distribution that is approximated by the sum of the zeroth- and first
      order Legendre polynomial in diffusion theory, or the sum of isotropic and
      coherent components in transport approximation. The method is then used to
      calculate reflectance from a half-space blood medium. It is found that first
      order scattering flux alone produces a good agreement with experimental data and
      higher-order scattering fluxes are negligible in whole blood.

PMID- 9556968
TI  - Open-loop tracking performance of a limb joint controlled by random, periodic,
      and abrupt electrical stimulation inputs to the antagonist muscle pair.
AB  - The ability of the cat's ankle joint to track various input signals when
      controlled by electrically elicited motor unit recruitment, firing rate and
      antagonist muscle coactivation was examined. Pseudo-random, sinusoidal and
      staircase signals were used to control the soleus and tibialis anterior muscles
      isometrically and with a 250-g pendulum. Tracking was evaluated through cross
      correlation for pseudo-random and sinusoidal signals, and by rise time and steady
      state error in step signals. Better tracking was obtained in isometric conditions
      than in load-moving conditions. Pseudo-random signals resulted in 250-ms delay
      between input and isometric torque output. For load-moving conditions, 340-ms and
      400-ms delay in torque and angle were obtained. For sinusoids, delays decreased
      from 240 ms at 0.5 Hz, to 140 ms at 2 Hz in isometric conditions. Time delays for
      angle were between 300 and 400 ms, decreasing as frequency increased. Poor cross
      correlation was found for torque in load-moving conditions, because of pendulum
      nonlinear dynamics. Step size was not uniform in staircase trials, with steady
      state errors between 9% and 39%, and rise times between 200 and 1000 ms. It is
      concluded that open-loop joint control results in poor tracking, presumably
      because it is devoid of feedback mechanisms.

PMID- 9556969
TI  - Fields and currents in the organs of the human body when exposed to power lines
      and VLF transmitters.
AB  - A study is made of the electric fields and currents induced in the organs of the
      human body when exposed to high-voltage 50-60-Hz transmission lines and 10-30-kHz
      high-power transmitters. Relevant analyses previously carried out are summarized
      and supplemented with detailed investigations that complete the picture.
      Incomplete, misleading, and incorrect statements and methods in the related
      literature are pointed out, completed, and corrected. The major contribution is
      to provide quantitatively accurate, relatively simple analytic formulas that
      relate the incident electric field to the induced field in the organs of the
      body. The formulation and solution of the underlying integral equation are
      carried out in the Appendix.

PMID- 9556970
TI  - Effect of electrode size on impedance images of two- and three-dimensional
      objects.
AB  - The sensitivity of an impedance imaging system to small cylindrical
      inhomogeneities in two-dimensional (2-D) and three-dimensional (3-D) saline tanks
      was studied for different height electrodes and different height targets.
      Experimental results were compared with analytical models. Inhomogeneities in the
      3-D tank having limited vertical extent were detected by electrodes of vertical
      size comparable to that of the inhomogeneity. Taller electrodes had increased
      sensitivity to short targets to only a limited extent. When the electrode height
      was more than twice that of the target, sensitivity decreased or remained the
      same with further increases in electrode height. The system was less sensitive to
      inhomogeneities in the 3-D tank than to those in the 2-D tank. The
      distinguishability of conductors was greater than that of insulators in the 3-D
      tank, and the opposite was true in the 2-D tank, consistent with an analytical
      result.

PMID- 9556971
TI  - A note on the compartmental analysis and related issues in laser Doppler
      flowmetry.
AB  - Compartmental analysis (CA) in laser Doppler flowmetry (LDF) means deciphering
      the nutritional and thermoregulating flows from the measured perfusion flux.
      Based on the new theories proposed in [1] and [2], the CA is formulated here as
      an optimal approximation without directly involving the geometric information of
      the vessel network. It is seen that this approximation approach could also solve
      the biological zero (BZ) problem simultaneously, therefore, it actually provides
      a systematic solution to the BZ problem without estimating the BZ flux
      experimentally. In addition, the BZ problem with compartmental differences is
      reformulated, and the condition under which multiple compartments can be treated
      as a single one is investigated. The result, together with some computer
      simulations, showed that the theory in [2] is still an easy and useful
      approximation in practice. This note serves as an useful supplement to [1] and
      [2] and may help to solve and clarify some critical problems in LDF.

PMID- 9556972
TI  - Localized prior knowledge and optimal interpolation in high-resolution
      tomography.
AB  - The problem of electromagnetic tomographic reconstruction is approached in terms
      of the derivation of a minimum norm interpolator, incorporating a priori
      knowledge gained from a previous reconstruction. An algorithm is suggested for
      the initial estimate and both images are compared to that of bilinear
      interpolation.

PMID- 9556973
TI  - [Increased antibiotic resistance in severely ill patients].

PMID- 9556974
TI  - [Thiazolidindiones in type II diabetes mellitus].

PMID- 9556975
TI  - [Cell cycle and cancer].

PMID- 9556976
TI  - [Echinococcosis. Detection, prevention and control].

PMID- 9556977
TI  - [Melatonin. Physiology, pathophysiology and possible therapeutic approaches].

PMID- 9556978
TI  - [Finasteride or sabal extract in acne?].

PMID- 9556979
TI  - [Medical education: 'plus ca change, plus c'est la meme chose'].
AB  - Medical curricula are being overhauled at increasingly short intervals. Fashion
      is one of the driving forces behind the changes, sometimes at the expense of
      reason. There is no scientific proof that one type of curriculum produces better
      doctors than an other. A caring and humanistic attitude in physicians is probably
      less dependent on specific training than on innate personality traits and the
      example of role models. The Dutch Journal of Medicine is launching two
      initiatives intended to contribute to the education of medical students: an
      almost free subscription is offered after the first year, and a (quarterly)
      student edition will appear from 1998.

PMID- 9556980
TI  - [How to continue after an error in family practice?].
AB  - Not just malfunctioning doctors make mistakes and errors, all doctors do.
      Patients suffer through errors, while the doctor is burdened by feelings of guilt
      and self-reproach. Furthermore the taboo on errors in medicine impedes doctors
      from learning from mistakes. Adequate management of these situations is of great
      importance. In order to minimise emotional damage to the patient and his
      relatives and to improve the quality of medical practice, acknowledgement of
      having made a mistake comes first; the general practitioner should be aware of
      personal defence mechanisms such as projection, denial or rationalisation. He
      should share his experience with some colleagues; in an atmosphere of trust the
      emotions of regret, shame and anger can be aired. Next the peer group assists in
      analysing the incident step by step. This analysis makes it possible to learn
      from the error and perhaps to take measures to prevent recurrence. Thereafter
      management with respect to the patient or his relatives should be established
      with aid of the group. Guidelines are: make an appointment with the patient
      without delay; take ample time and avoid disturbance; listen to the patient and
      respect his feelings; express regret with regard to the consequences for the
      patient; contact the patient again after an interval to check if new questions
      have arisen. This approach is helpful in restoring the patient-doctor relation
      after a mistake.

PMID- 9556981
TI  - [Clinical drug research in children: current international guidelines. Committee
      for Proprietary Medicinal Products].
AB  - Drugs research in children entails a number of problems: medical-ethical,
      pharmacological (owing to the immaturity of the organs and the growth and
      development of the child) and financial (because children do not use many drugs).
      Consequently, children are exposed to insufficiently tested drugs and new
      therapeutic possibilities are withheld from them. Currently, little clinical
      drugs research in children is being carried out, but this is about to change. By
      now, European guidelines have been drawn up for the performance of clinical drugs
      trials according the 'good clinical practice' standards in children. In the
      Netherlands, a cooperative body has been set up (the Pediatric Pharmacology
      Network), which is to promote and coordinate paediatric pharmacological research
      in according with these guidelines.

PMID- 9556982
TI  - [Neurosurgical stereotactic treatment in Parkinson's disease].
AB  - For patients with Parkinson's disease who have become unresponsive to
      pharmacotherapy or have developed severe motor complications due to medical
      therapy, a number of symptomatic neurosurgical interventions are available:
      thalamotomy, thalamic stimulation and pallidotomy. These stereotactic operations
      are performed under local anaesthesia. The target is located using anatomical and
      physiological techniques, after which the neuro-ablative or neuromodulatory
      procedure is performed. The choice of the target depends on the symptoms of the
      patient that most impair daily functioning. In case of dominating tremor,
      thalamic surgery is performed. Patients who are mainly incapacitated by rigidity,
      hypokinesia or pharmacotherapy-induced dyskinesias are suitable candidates for
      pallidotomy. Contraindications are cognitive dysfunction, severe disturbance of
      gait and balance, advanced cerebral atrophy on CT or MRI, limited life expectancy
      and a poor general condition enhancing surgical risk, e.g. coagulation disorders
      or uncontrolled hypertension. Surgical treatment of Parkinson's disease is being
      carried out in clinical trials in the Netherlands in the Academic Medical Centre
      in Amsterdam, the Academic Hospital in Groningen and the St. Elisabeth Hospital
      in Tilburg.

PMID- 9556983
TI  - [Immunology in clinical practice. VIII. Role of cytokines in the pathogenesis of
      bacterial infections].
AB  - Cytokines are small proteins that can be produced by many different cell types
      involved in inflammation. The cytokine network consists of pro-inflammatory
      cytokines, facilitating inflammation, and anti-inflammatory cytokines, reducing
      inflammation at least in part by inhibiting the production of pro-inflammatory
      cytokines. The production of cytokines is enhanced during bacterial infections.
      The balance between pro- and anti-inflammatory cytokines critically determines
      the outcome of infection. Excessive systemic release of pro-inflammatory
      cytokines such as tumour necrosis factor alpha and interleukin 1 may contribute
      to organ failure in patients with fulminant sepsis. On the other hand, the local
      action of pro-inflammatory cytokines, at the site of a compartmentalized
      infection, is required for an adequate host antibacterial defence. Therefore,
      neutralization of pro-inflammatory cytokines may benefit some patients with
      bacterial sepsis but harm others.

PMID- 9556984
TI  - [Communication disorders in children; experiences with a multidisciplinary
      outpatient diagnosis].
AB  - Communication disorders in children can be caused by impaired hearing. However,
      also other factors can adversely influence speech and language development, such
      as mental retardation, lack of language stimulation and anatomical defects of
      speech organs. Speech and language development can be regarded as a symptom;
      therefore a multidisciplinary diagnostic procedure is essential to the planning
      of an adequate therapy programme. In the Netherlands a great variety in diagnosis
      and treatment exists. A child with a communication disorder is usually seen by
      five specialists, and the interval between recognition of the communication
      problem by the parents and the final diagnosis, after which therapy starts,
      sometimes lasts almost three years. Besides that, in a majority of cases speech
      and language therapy is offered. In order to change this process for the better a
      prospective research programme was started in the Academic Hospital Groningen,
      the Netherlands, with a protocolled multidisciplinary diagnostic approach. The
      first findings are encouraging: 89% of 209 children with supposed communication
      disorders were diagnosed after one visit to the outpatient clinic.

PMID- 9556985
TI  - [Incidence of postoperative wound infections in The Netherlands].
AB  - OBJECTIVE: To inventory postoperative infections in Dutch hospitals. DESIGN:
      Descriptive study. SETTING: National organization for quality assurance in
      hospitals, Utrecht, the Netherlands. METHOD: In 36 Dutch hospitals data on
      surgical patients, surgical site infections and risk factors were collected,
      using standardised methods, as part of a quality system by which hospitals could
      compare their infection rates with the rates in the database. RESULTS:
      Surveillance of surgical site infections was introduced in 36/118 (31%)
      hospitals. Data on 32,869 surgical procedures were collected, 1115 (3.4%)
      surgical site infections were found. The infection rates by wound contamination
      class varied from 2.2% (95% confidence interval (CI): 2.0-2.4) in clean wounds to
      11% (95% CI: 9.3-12.8) in dirty wounds; the infection rates by duration of
      operation varied from 3% (95% CI: 2.8-3.2) in operations lasting less than two
      hours to 10.8% (95% CI: 6.0-18.5) in operations lasting more than 8 hours; the
      infection rate by ASA classification varied from 2.7% (95% CI: 2.3-3.2) in class
      I to 15.5% (95% CI: 8.4-26.5) in patients in class IV. Advanced age, emergency,
      preoperative stay were recognised as risk factors. The infection rates in the
      most frequently recorded types of operation varied from 0.2% (95% CI: 0.0-1.1) in
      varicose veins to 9.8% (95% CI: 7.2-13.2) in femoral bypass grafts. The use of
      antimicrobial prophylaxis varied per type of operation. The micro-organisms most
      frequently isolated were Staphylococcus aureus. Staphylococcus epidermidis,
      Pseudomonas aeruginosa, and Escherichia coli. Of the infections 32% were
      identified in the first week following surgery. Of the infected patients 88%
      stayed in hospital during one or more days following the onset of infection.

PMID- 9556986
TI  - [Prevalence of mental disorders in persons with Parkinson's disease].
AB  - OBJECTIVE: To determine the prevalence of cognitive disorder, depression, anxiety
      and psychotic symptoms in persons with Parkinson's disease in the general
      population. DESIGN: Cross-sectional study. SETTING: The Netherlands. METHOD:
      Between May and September 1995, a random sample of 384 persons with Parkinson's
      disease (members of the Parkinson's disease patient organisation plus 24 Dutch
      nursing home patients) were investigated with the Composite International
      Diagnostic Interview (CIDI) and the General Health Questionnaire (GHQ-12).
      RESULTS: The 1-month prevalence of DSM-III-R psychiatric disorder was 39.1%, of
      which 13.3% cognitive impairment, 5.5% depression (2.3% major depression and 4.7%
      dysthymia), and 24.5% anxiety disorder (4.9% agoraphobia and 11.5% social
      phobia). Psychiatric comorbidity mainly concerned anxiety disorder, in
      combination with depression (21%) or cognitive disorder (28%). Four out of ten
      persons who ever had a depression or anxiety disorder, developed the first
      episode after the onset of Parkinson's disease. CONCLUSION: The prevalence of
      psychiatric disorder in persons with Parkinson's disease was high, compared with
      figures of the general population, notably for anxiety and cognitive disorder,
      but not for depression.

PMID- 9556988
TI  - [3 patients with accidental hypothermia; customized rewarming].

PMID- 9556987
TI  - [Sudden death in young persons caused by arrhythmogenic right ventricular
      dysplasia].
AB  - A previously healthy boy aged 14 developed persistent ventricular tachycardia
      while engaged in sports; ultrasonography revealed arrhythmogenic right
      ventricular dysplasia (ARVD). He was treated with a class III antiarrhythmic drug
      but nevertheless died 4 years later during recreational activities. An uncle of
      the boy was found to have died suddenly on a playing field, 25 years previously
      at the age of 20. In ARVD, fibrolipomatous areas in the right ventricle lead to
      dilations of the wall where (sometimes fatal) re-entrant tachycardias may
      develop. An autosomal dominant heredity with variable expression and penetrance
      is considered probable, while the genetic defect was located recently.
      Examination and, if necessary, pharmacotherapy of relatives of an ARVD patient
      may reduce the risk of a fatal arrhythmia.

PMID- 9556989
TI  - [Treatment of genital prolapse in very old women].

PMID- 9556990
TI  - [Treatment of genital prolapse in very old women].

PMID- 9556991
TI  - [Treatment of genital prolapse in very old women].

PMID- 9556992
TI  - [Pain control in the final stage of life].

PMID- 9556993
TI  - [Combination of anxiety disorder and alcohol dependence].
AB  - Three patients, two men aged 47 and 37 and a woman aged 32, are described. All
      three suffered from a combination of alcohol addiction and anxiety disorder. None
      of them had previously received adequate treatment because on the one hand they
      had been refused by psychiatric institutes because of their alcohol addiction,
      and on the other the institutes for the care of addicted had not diagnosed the
      anxiety disorder. About 150,000 people are estimated to have both an alcohol
      addiction and an anxiety disorder in the Netherlands. The importance of making a
      correct diagnosis and providing proper treatment for both disorders is
      emphasized.

PMID- 9556994
TI  - [Lactation-induced amenorrhea as birth control method].
AB  - Improving access to quality care in family planning, a recent document of the
      World Health Organization, reviews the epidemiological and clinical evidence
      relevant to medical eligibility of well established contraceptive methods.
      Breastfeeding is widely regarded as unreliable for individual contraception. The
      document, however, argues that the lactational amenorrhoea method (LAM) is a safe
      and effective family planning method. Worldwide, LAM is the most important way of
      fertility regulation and its efficacy is confirmed in many studies, with a 2%
      risk of pregnancy in the first six months after birth. Taking into account
      certain well defined conditions (frequent feedings, no supplementary feeding
      before 4-6 months, method only to be used in the absence of menstruation), LAM
      can be relied on for contraceptive protection for up to 1 year post partum.

PMID- 9556995
TI  - [Rehabilitation possibilities for hearing-impaired subjects].
AB  - Hearing impairment is a symptom, not a diagnosis. A number of types of hearing
      impairment can be distinguished. The self-reported hearing problems cluster
      around six hearing factors, the most important of which are speech understanding
      in noise and localisation of a sound source. For these capabilities equivalent
      functioning of both ears is important. The general practitioner can determine
      diagnosis and severity of the impairment using rather simple tools. When the
      cause of the impairment cannot be reduced in a proper way an adaptation of the
      sound to the impaired ear will be indicated. This can be arranged by either an
      ENT specialist or a centre for audiology. The selection of a proper hearing aid
      requires expertise and particular attention for the complaints. It is of the
      utmost importance that the hearing-impaired person can try out the effects of the
      hearing aid in daily circumstances for some weeks. If the patient, members of the
      family or the prescriber are not satisfied with the results, supplementary help
      is required, for example training in communication skills or special devices.

PMID- 9556996
TI  - [Myocardial tissue vitality: clinical relevance, pathophysiology and
      identification].
AB  - Heart failure is an increasing clinical problem because of the rising frequency
      of admissions and the high mortality. Excellent long-term results are obtained
      with heart transplantation, whereas the long-term prognosis is poor when patients
      are treated medically. It has recently been demonstrated that, in patients with
      depressed left ventricular (LV) function, revascularization may be an alternative
      form of therapy, since improvement of LV function, which is an important
      prognostic factor, may occur after coronary revascularization. Recovery of LV
      function after revascularization may occur in patients with dysfunctional but
      viable myocardium, whereas no recovery can be expected in patients with scar
      tissue. Improvement of LV function after revascularization can be explained on
      the basis of the concept of myocardial tissue vitality': chronically ischaemic
      myocardium temporarily loses the facility to contract, but the contraction is
      regained after revascularization (once the ischaemia is eliminated). For the
      selection of patients who may profit by a revascularization procedure, techniques
      have been developed for the identification of dysfunctional but viable tissue.
      The myocardial glucose metabolism can be visualized by administration of 18F
      desoxyglucose (FDG) and imaging by positron emission tomography or 'single photon
      emission computer tomography'. Vital tissue shows diminished perfusion with
      intact glucose metabolism (FDG perfusion mismatch); a vital tissue shows
      diminished perfusion without glucose metabolism (FDG perfusion match).
      Scintigraphy of the membrane of the myocardial cell can also be investigated
      using 201Tl scintigraphy. Reserve contractility of the myocardium can be
      visualized by echocardiography during administration of dobutamine.

PMID- 9556998
TI  - [Inventory and follow-up of patients with surgery for (uterine) vaginal prolapse,
      combined with or without, (masked) stress incontinence].
AB  - OBJECTIVE: Evaluation of the development or persistence of urinary stress
      incontinence in patients operated on because of prolapsed uterus, with
      cooperation between gynaecologists and urologists. DESIGN: Retrospective.
      SETTING: Department of Gynaecology and Obstetrics, Leyenburg Hospital, The Hague,
      the Netherlands. METHODS: In 178 patients subjected to prolapse correction in the
      period 1992-1996, presence of urinary incontinence was analysed by means of a
      written enquiry after an average of 22 months. The 91 patients who had visited
      the gynaecological outpatient clinic and were seen together with a urologist,
      were subjected to urodynamic examination in the absence of symptoms of stress
      incontinence and were operated in cooperation with the urologist. Four groups
      were distinguished on the basis of preoperative features: group I (n = 37) with
      manifest stress incontinence, group II (n = 22) with masked stress incontinence,
      group III (n = 32) in whom no (masked) stress incontinence could be demonstrated
      and group IV (n = 87) not subjected to urodynamic examination. The patients of
      groups I and II, in addition to prolapse correction, were also subjected to
      urethral suspension. RESULTS: Twenty-five (68%) of the group with manifest stress
      incontinence were free of stress incontinence after the operation, while eight
      patients (22%) reported improvement (a total of 89%). In 22 of the 54 patients
      (41%) who preoperatively had no incontinence symptoms, urodynamic examination
      revealed a masked stress incontinence. Sixteen of them (73%) did not develop
      symptoms of stress incontinence after the operation, while eight (15%) did
      develop such symptoms. Thirty of the 32 patients (94%) who preoperatively had no
      (masked) stress incontinence remained symptom-free. Out of 64 patients without
      preoperative incontinence, who were operated without urological cooperation, 12
      (19%) developed stress incontinence.

PMID- 9556999
TI  - [Consensus antithrombotic prophylaxis of vascular incidents in patients with
      manifest atherosclerotic vascular diseases. Central Guidance Organization for
      Peer Review].
AB  - The consensus on antithrombotic prophylaxis of vascular incidents in patients
      with manifest atherosclerotic vasculopathy was preceded by a systematic
      classification of results from relevant articles according to 'evidential value':
      from randomized prospective trials of sufficient quality and size, via less
      adequate or non-randomized trials to the current opinion in the Netherlands. The
      principal advice was to prescribe antithrombotic prophylaxis, mostly
      acetylsalicylic acid, for patients with manifest atherosclerotic vasculopathy (in
      head, heart and (or) legs). With regard to the question what drug should be
      preferred for patients with intermittent claudication, no consensus could be
      reached for lack of adequate research. Acetylsalicylic acid is not more effective
      in higher than in lower doses, but in higher doses it has more side effects;
      therefore lower doses are preferred: 80-100 mg per day, and for neurological
      indications, 30 mg or more per day. Use of coumarin derivates is only to be
      preferred in patients with atrial fibrillation who have suffered a TIA or a non
      crippling cerebral infarction, in patients with atrial fibrillation and a cardiac
      disorder such as large myocardial infarction or a left ventricular aneurysm, and
      in patients who have undergone a cardiac valve operation. Since the proportion of
      pros and cons of antithrombotic prophylaxis may change during a patient's life,
      the indication should be reconsidered periodically.

PMID- 9557000
TI  - [Seroprevalence of human T-cell lymphotropic virus type I in Curacao and
      predictive variables for that infection].
AB  - OBJECTIVE: To determine the seroprevalence of human T-cell leukaemia virus (HTLV)
      type I and predictive variables in Curacao. DESIGN: Descriptive. SETTING: St.
      Elisabeth Hospital, Curacao. METHODS: A total of 2531 sera were randomly
      collected from a total population of approximately 145,000 over a period of three
      months (of seven the sex was not known). An initial ELISA test was performed to
      detect anti-HTLV-I antibodies. If this test was positive an ELISA re-test (in
      duplicate) was performed. If one of these re-tests was found positive a western
      blot confirmation test was performed. The association with age, sex, social class
      and history of syphilis were analysed with multiple logistic regression models
      and adjusted for confounding. RESULTS: The estimated prevalence of HTLV-I was
      1.9% (49/2524). No significant sex differences were observed (odds ratio (OR):
      1.13; 95% confidence interval (95% CI): 0.62-2.05). Increasing age (p for trend =
      0.0003) and lower social class (OR: 1.86; 95% CI: 1.03-3.38) were important
      predictive factors for HTLV-I infection. Members of the lower social classes and
      persons 50 years or older were at relatively high risk (OR: 3.91; 95% CI: 2.21
      6.94). CONCLUSION: HTLV-I infection is endemic in the island of Curacao, as in
      other Caribbean islands. The estimated prevalence is 1.9%. Age and lower social
      class were important predictive factors for HTLV-I infection.

PMID- 9557001
TI  - [Progressive myelopathy caused by human T-cell lymphotropic virus type I (HTLV-I)
      in 3 patients in The Netherlands].
AB  - One man and two women (aged 30, 44 and 46, respectively) were seen between 1987
      and 1992 with a myelopathy caused by the human T-cell lymphotropic virus type I
      (HTLV-I). The first symptoms were impaired gait in the man and micturition
      disorders in the women. Diagnosing took 2 to 4 years, possibly due to the fact
      that many Dutch physicians are unfamiliar with the disease. The diagnosis was
      based on originating from an endemic area (i.e. Surinam and the Caribbean basin),
      the clinical picture and the presence of antibodies against HTLV-I in blood and
      CSF. The disease in a number of years leads to spastic paraparesis, incontinence
      for urine and dependence on a wheelchair.

PMID- 9557002
TI  - [Effect of protein restriction on deterioration of kidney function].

PMID- 9557003
TI  - [Dutch drug registration: more openness highly desired].

PMID- 9557004
TI  - [Thyroglossal cyst].
AB  - The thyroglossal cyst is a wellknown cause of a swelling in the neck. The
      generally accepted technique of treatment was described in 1928, but many
      recurrences are still seen in daily clinical practice. The radical technique of
      removal of cysts and sinuses of the thyroglossal duct according to Sistrunk is
      the method of choice. Over an 8-year period 40 cases were treated in this fashion
      in the University Hospital Groningen, the Netherlands, with an average follow-up
      of 5 years and 3 months; in 29 it was the first operation. Only 1 patient of the
      23 treated according to Sistrunk had a recurrence for which he had to be treated
      again. Six patients were treated otherwise; 3 of them had a recurrence. It is
      concluded that the first surgery (according to Sistrunk), if correctly performed,
      offers the best chance for cure.

PMID- 9557005
TI  - [Ovum fertilization using surgically obtained sperm: additional risk to offspring
      unlikely with meticulous procedure].
AB  - In the Netherlands a presumed higher risk of transmission of genetic
      abnormalities to the offspring in programmes of intracytoplasmatic sperm
      injection (ICSI) using surgically retrieved sperm (microscopic epididymal sperm
      aspiration (MESA) or testicular sperm extraction (TESE)) has triggered a
      moratorium. However, the ICSI-MESA/TESE-programme should be resumed under
      conditions for the following reasons: the source of the sperm is not a accurate
      standard of its genetic contents: the cause of the male infertility and the
      morphology and function of the injected spermatozoon appear to be better
      criteria; animal experiments and clinical results are reassuring as to the
      proposed risk; it is uncertain whether the complex genetical mechanisms involved
      in spermiogenesis and sperm maturation can be unraveled in the laboratory in due
      course; the exodus of patients to neighbouring countries will be stopped and
      biological material necessary for human research will become available. The
      conditions are that (a) only morphologically normal and motile sperm should be
      used, (b) ICSI should be preceded by genetical screening and succeeded by long
      term follow up of the offspring.

PMID- 9557006
TI  - [Last word on hormone replacement and breast cancer?].
AB  - A very large meta-analysis of the Collaborative Group on Hormonal Factors in
      Breast Cancer has revealed an increasing risk of breast cancer with longer
      durations of use of hormonal replacement therapy (HRT). This risk increase is
      restricted to current users of HRT or women who ceased use recently. A 35%
      increase of the relative risk of breast cancer was found after 5 years of HRT use
      or longer. After cessation of HRT use the excess breast cancer risk disappeared
      in 5 years, even after long durations of use. The risk increase was greater for
      women of normal or lean body weight than for more obese women. Tumours found in
      women who ever used HRT were diagnosed at a lower clinical stage, which suggests
      that enhanced screening might be involved. However, the increased breast cancer
      mortality in HRT users, as found in other studies, rather suggests a biologic
      mechanism Long-term use of HRT is not yet common in the Netherlands, but an
      increasing trend is present. Thus, the benefits of long-term use of HRT must be
      carefully weighted against the risks.

PMID- 9557007
TI  - [Hormone replacement therapy following breast carcinoma].
AB  - Additional advantages of hormone suppletion therapy (HST) in women with
      climacteric complaints are the reduced risks of development of cardiovascular
      disease and osteoporosis. A disadvantage is the enhanced risk of breast cancer.
      More and more women with a treated primary breast cancer nowadays have a
      relatively favourable prognosis; they might also profit by HST, especially if
      chemotherapy for breast cancer has led to an early menopause. Recent pilot
      studies of the connection between HST and recurrence of breast cancer are
      inadequate as to methodology and size to permit definite conclusions. There are
      numerous arguments for a connection between exposure to oestrogens and
      development of breast cancer. As long as it has not been demonstrated that HST
      does not lead to enhanced risk of breast cancer recurrence, the general
      recommendation should be not to administer HST to patients with treated breast
      carcinoma.

PMID- 9557008
TI  - [Immunology in clinical practice IX. Systemic vasculitis].
AB  - A diagnosis of vasculitis generally requires histopathological proof of
      vasculitis, particularly because many other disease entities may mimic vasculitis
      ('vasculitis-look-alikes'). Vasculitis can be primary (idiopathic) or secondary
      to other diseases, especially infectious diseases. The primary vasculitides are
      classified according to the size of the vessels involved and the nature of the
      inflammation, in combination with clinical symptoms. The detection of
      autoantibodies, particularly the antineutrophil cytoplasmic antibodies (ANCA), in
      some of the primary vasculitides, has facilitated the diagnosis of those diseases
      and has given more insight into their pathophysiology. Treatment of primary
      vasculitis still consists of corticosteroids whether or not in combination with
      immunosuppression. New insights in pathophysiology may provide more specific and
      less toxic treatment modalities.

PMID- 9557009
TI  - [Nitric oxide inhalation in newborn infants with pulmonary hypertension].
AB  - Nitric oxide (NO) is an important endogenous vasodilator. NO, produced in the
      endothelial cell, causes vasodilation by relaxation of the vascular smooth muscle
      cell. Inhalation of NO plays a role in the treatment of persistent pulmonary
      hypertension of the newborn, a syndrome with considerable morbidity and
      mortality. NO inhalation specifically leads to pulmonary vasodilation without
      systemic hypotension, since NO binds avidly to haemoglobin. Neonates with
      pulmonary hypertension associated with lung hypoplasia, meconium aspiration
      syndrome, infantile inspiratory distress syndrome due to surfactant deficiency,
      and sepsis have been treated with inhaled NO. Literature data on NO inhalation
      and experience in our units with NO inhalation show an improvement in arterial
      oxygen tension and a decreased need for extracorporeal membrane oxygenation, but
      no reduction in mortality. NO toxicity as a result of NO inhalation in the
      newborn has not been reported yet.

PMID- 9557010
TI  - [Increase in number of premature births in The Netherlands: comparison of 1983
      and 1993. Scientific Guidance Commission of the National Neonatology
      Registration].
AB  - OBJECTIVE: Survey of changes in the number of preterm and very low birth weight
      infants in the Netherlands in ten years. DESIGN: Descriptive. SETTING: TNO
      Preventive en Gezondheid, sector Jeugd, Leiden, the Netherlands. METHODS: All
      infants with a gestational age less than 32 weeks and (or) a birth weight less
      than 1500 g from the National Neonatal Register born in 1993 were selected,
      supplemented with data from a questionnaire for hospitals not taking part in the
      register. The data were compared with those on similar infants from the 'Project
      on preterm and small for gestational age' infants born in 1983. RESULTS: The
      total number of preterm and very low birth weight infants increased from 1423 in
      1983 to approximately 1882 in 1993. There was also an increase in terms of
      proportion, from 8.4 per thousand to 9.6 per thousand. The proportion of preterm
      infants never treated in a neonatal intensive care unit decreased from 40% in
      1983 to 14% in 1993, probably due to increased centralization of neonatal
      intensive care facilities. In the same time mortality decreased for all
      gestational age categories. CONCLUSION: Both the total number and the survival of
      preterm and very low birth weight infants increased considerably over a decade.
      This caused a considerable increase in intensive care days and is therefore an
      important reason for the increased requirement of neonatal intensive care cots.

PMID- 9557011
TI  - [Increase in perinatal referral to regional centers of premature birth in The
      Netherlands: comparison 1983 and 1993].
AB  - OBJECTIVE: To determine changes in referral of preterm newborns. DESIGN:
      Descriptive. SETTING: Foundation for Perinatal Epidemiology the Netherlands,
      Leiden. METHODS: Data regarding hospital of birth, referral, need of intensive
      care and mortality of the infants < 32 weeks and (or) < 1500 g birth weight born
      in 1993 from the National Neonatology Register were supplemented with data from a
      questionnaire for hospitals not included in the register. The data were compared
      with those of similar infants from the 'Project on preterm and small for
      gestational age', born in 1983. RESULTS: In 1983, 61% of the preterm infants were
      treated in a perinatal centre: 39% were not referred. In 1993 these numbers were
      89% and 11%, respectively. The contribution of antenatal referral increased from
      29% to 47% while that of postnatal referral decreased from 41% to 25%. Mortality
      decreased from 25.4% in 1983 to 14.3% in 1993. CONCLUSION: Regionalization of
      high risk perinatal care resulted in concentration of care for preterm infants.
      At the same time, in-hospital mortality decreased by almost 50%.

PMID- 9557012
TI  - [Impediments to incubator home care in The Netherlands].
AB  - OBJECTIVE: To determine whether incubator home care is desirable and feasible.
      DESIGN: Inventory. SETTING: Four neonatal units representative of the type of
      care in general hospitals in the Netherlands. METHOD: The relevant data on all
      infants with a birth weight < or = 2000 g admitted in the last 3 months of 1996
      to one of four hospitals were analysed. Conditions for incubator home care were
      determined (e.g. absence of need for special care, vital function monitoring or
      nasogastric tube feeding). RESULTS: Forty-nine infants were enrolled. Mean
      hospital stay was 28.7 days in an incubator plus 19.7 days in a cot. When infants
      were placed in a cot they usually still needed tube feeding and monitoring of
      vital functions and sometimes parenteral nutrition, medication or extra oxygen
      which made home discharge impossible. Therefore a pilot study of actual home care
      could not be carried out. CONCLUSION: Although early home discharge is very
      desirable for newborn infants, the number of infants eligible for incubator home
      care is so small that further attempts to organise it are not useful.

PMID- 9557013
TI  - [Sequelae of premature birth: substantial medical consumption and physical
      limitations; survey among parents of 10-year-olds].
AB  - OBJECTIVE: To determine health and disabilities of preterm infants at age 10.
      DESIGN: Prospective follow-up study. SETTING: TNO Preventive en Gezondheid,
      sector Jeugd. Leiden, the Netherlands. METHOD: A questionnaire on medical
      consumption and physical disabilities was sent to the parents of a Dutch cohort
      of infants born alive in 1983 with a gestational age < 32 weeks and (or) a birth
      weight < 1500 g. The data were compared with outcomes at 5 years of age and with
      a peer group in mainstream education (data collected in a representative sample
      from the school health care system). RESULTS: Questionnaires on 75% of the
      eligible children were returned. Almost 40% of the preterm children had been
      admitted to hospital after the age of 5. Children in special education were
      significantly more often treated by a physiotherapist and (or) speech therapist.
      Overall 45% of the children suffered from a physical disability. This was six
      times as frequent as in a peer group from the school health survey. Although the
      assessment of physical disabilities was based on a paediatric examination at age
      5 and on a parental questionnaire at age 10, differences were small. CONCLUSION:
      Mild developmental problems and learning disabilities are frequent in preterm
      infants. Research of preventive methods and timely interventions are needed and
      should be incorporated in the facilities for neonatal intensive care.

PMID- 9557014
TI  - [Iatrogenic tension pneumothorax following faulty positioning of gastric tube].
AB  - A 74-year-old man was admitted with respiratory insufficiency and required
      mechanical ventilation. Enteral nutrition was given via a nasogastric feeding
      tube, but persistent food retention occurred. The chest X-ray showed the
      nasogastric tube to be in the right pleural space. After the tube was withdrawn
      the patient developed a tension pneumothorax and a closed-tube thoracostomy was
      performed. The patient's recovery was uneventful, with resolution of the
      pneumothorax. It is necessary to be alert with respect to the tube position,
      which, if doubtful, should be checked by chest X-ray. Recognition of an aberrant
      position is necessary to minimize related morbidity.

PMID- 9557015
TI  - [Pill cycle disturbance in simultaneous use of itraconazole and oral
      contraceptives].
AB  - Since the introduction of itraconazole in the Netherlands, the Netherlands
      Pharmacovigilance Foundation LAREB and the Inspectorate for Health Care received
      15 reports of pill cycle disturbances and one of pregnancy occurring during
      simultaneous use of itraconazole and oral contraceptives. Twelve women used oral
      contraceptives containing ethinylestradiol and desogestrel. In these women, the
      withdrawal bleeding was either delayed or did not occur at all; one of these
      women reported a transiently positive pregnancy test after previous breakthrough
      bleedings. Three women who used a contraceptive containing ethinylestradiol and
      levonorgestrel had a breakthrough bleeding. One woman who used an oral
      contraceptive containing ethinylestradiol and cyproterone acetate became pregnant
      during the concomitant use of itraconazole. The possible mechanism involved
      remains to be explained. Although an influence of itraconazole on the reliability
      of oral contraceptives is uncertain, additional contraceptive measurements might
      be considered.

PMID- 9557016
TI  - [Health Council's report 'preoperative evaluation: reconsideration of basic
      assumptions'].

PMID- 9557017
TI  - [Prader-Willi syndrome in young infants].

PMID- 9557018
TI  - [Prader-Willi syndrome in young infants].

PMID- 9557019
TI  - ['Labor storm' following cervical ripening with prostaglandin gel].
AB  - In three pregnant women aged 26, 31 and 26 years with post-term pregnancy and
      (or) worsening preeclampsia and an immature cervix, parturition was induced by
      intracervical application of dinoprostone. This was followed within a few hours
      by bradycardia of the infants, with a labour frequency of about 5 per 10 minutes
      and contractions lasting at least 1 minute. After suppression of labour (in two
      patients, one of whom meanwhile had developed placental detachment), caesarean
      section was performed without delay. One child by then had sustained major
      cerebral damage: the other two recovered well. A potentially dangerous adverse
      effect of intracervical application of prostaglandin gel is excess uterine
      activity. The higher sensitivity to prostaglandins in several conditions
      complicating pregnancies (such as serotinicity and preeclampsia), may play a role
      in this complication. Careful application of the gel, adequate foetal monitoring
      and using half the normal dose in risk patients could be helpful in preventing
      foetal distress after intracervical application of prostaglandin gel.

PMID- 9557020
TI  - [Vision rehabilitation of patients with old-age macular degeneration].
AB  - Age-related degeneration of the macula retinae occurs in two forms: the serious
      form with invasion of blood vessels and leakage, and the atrophic form. Both
      forms ultimately lead to a central scotoma. The prevalence of the terminal stage
      of age-related macular degeneration varies from 1% in the age group 65-74 years
      to 11% in those 85 years or over. A total of 58,500 persons in the Netherlands
      have age-related macular degeneration and an estimated 22,000 persons depend on
      visual or optic aids. Aids for close vision are good illumination, magnification
      (reading glasses, magnifying glasses, telescopic lenses, television reading
      lenses (with possibility of changing contrast), large-letter books, playing cards
      with large symbols) and auditory aids. Aids for distant vision reduce troublesome
      light (sunglasses, filter) or enlarge the image (telescopic aids). Future new
      aids derive from modern computer technology (personal computer, integrated
      braille reader and speech synthesizer) or are based on opto-electronic image
      processing and presentation (mini-cameras with mini-VDUs in a sort of helmet).
      Effective use of aids depends on attention for the patient's desires and
      possibilities and on counselling in handling aids. Ophthalmological checkups
      remain useful for the prevention and (or) treatment of accessory disorders.

PMID- 9557021
TI  - [Allogeneic bone marrow transplantation in the treatment of (lysosomal) storage
      diseases].
AB  - The first report of a positive effect of allogeneic bone marrow transplantation
      (BMT) on the clinical course in a patient with a lysosomal storage disease was
      described in 1981. Since then, over 200 patients have been treated in this way
      but data are scarce and fragmentary. Allogeneic BMT involves replacement of the
      patient's haemopoietic system by that of a donor. The new cells that repopulate
      the body can correct the metabolic disturbance. Most experience with allogeneic
      BMT was gained in patients with mucopolysaccharidosis type I, metachromatic
      leukodystrophy and adrenoleukodystrophy. Allogeneic BMT reduces the amount of
      storage material in internal organs: skeletal abnormalities and neurological
      symptoms are at best stabilized. Transplantation-related mortality and morbidity
      are high. The applicability of allogeneic BMT is limited.

PMID- 9557022
TI  - [Clinical judgment and decision making in medical practice. A retiree with
      fatigue and foot drop].
AB  - A 64-year-old former civil servant consulted his general practitioner because of
      severe fatigue. Later he began to lose weight and gradually developed chronic
      sensorimotor polyneuropathy characterized by sensory nerve loss which started in
      his legs. After a year he needed a wheel chair and developed cachexia. IgG
      paraprotein was detected. Morbid-anatomical examination of enlarged
      supraclavicular lymph nodes revealed plasma cell angiofollicular hyperplasia,
      characteristic of Castleman's disease. Treatment with corticosteroids led to
      marked improvement of the patient's condition. He was able to walk again, using
      an ankle orthosis on both legs.

PMID- 9557023
TI  - [Characterization of 100 patients with tuberculosis treated in the Academic
      Medical Center in Amsterdam].
AB  - OBJECTIVE: To inventory both clinical and demographical data of patients with
      tuberculosis in the AMC, as well as diagnostic procedures, response to therapy
      and rate of resistance. DESIGN: Retrospective, descriptive. SETTING: The Academic
      Medical Center. Amsterdam, the Netherlands. METHOD: The medical records of all
      patients with a bacteriologically confirmed infection with Mycobacterium
      tuberculosis complex between January 1993 and December 1995 were studied.
      RESULTS: 70 out of 100 patients with tuberculosis were not born in the
      Netherlands. Out of 50 patients tested 18 were HIV positive. The most common
      abnormality seen on X-rays of non-HIV positive patients were caverns. The X-ray
      of HIV positive patients showed no abnormalities in 39%; there was no correlation
      with CD4 cell count. In 74% of the patients with pulmonary tuberculosis the
      diagnosis was made by culture of the sputum. Treatment consisted of INH,
      rifampicin, pyrazinamide and ethambutol. Twelve patients were infected with
      resistant strains, of which two were multidrug resistant. Four patients died of
      tuberculosis. CONCLUSION: Tuberculosis was seen mostly among immigrants. Only
      half the patients with tuberculosis were tested for presence of HIV antibodies.
      Culture and staining of sputum played a key role in the diagnosis of
      tuberculosis. Multiresistant tuberculosis was present in 2% of the patients.
      Death due to tuberculosis in this population was 4%.

PMID- 9557024
TI  - [Tuberculosis in HIV-positive and HIV-negative drug users in Amsterdam].
AB  - OBJECTIVE: To determine and to compare the incidences of active tuberculosis in
      HIV positive and HIV negative drug users and to describe the main characteristics
      of the tuberculosis cases. DESIGN: Prospective. SETTING: Municipal Health
      Service, Amsterdam, the Netherlands. METHOD: Data of the ongoing cohort study of
      HIV infection in Amsterdam drug users, including HIV serostatus and CD4 cell
      counts, from 1986 until 1996 were completed with data from the tuberculosis
      registration of the tuberculosis department of the Amsterdam Municipal Health
      Service and analysed statistically. RESULTS: Of 872 participants 24 persons
      developed culture confirmed tuberculosis during a total follow-up period of 4000
      person years (py) (0.6 per 100 py). Nineteen persons were HIV positive (1.54 per
      100 py) and 5 HIV negative (0.18 per 100 py). Multivariately, HIV infection and
      higher age increased the risk of tuberculosis substantially (relative risks 12.9;
      95% confidence interval (CI): 3.4-48.8 and 6.8: 95% CI: 1.3-35.0 respectively).
      Thirteen of 22 pulmonary tuberculosis cases (59%) were detected by half-yearly X
      ray screening of the chest. Tuberculosis occurred relatively early in the course
      of HIV infection at a mean CD4 cell number of 390/microliter. All but one patient
      completed the tuberculosis treatment. CONCLUSION: HIV infection increases the
      risk of active tuberculosis in Amsterdam drug users 13-fold. The incidence of
      tuberculosis in HIV negative drug users in 6 times higher than that in the
      overall Amsterdam population. Periodic chest X-ray screening contributes
      substantially to case-finding of active tuberculosis in Amsterdam drug users.

PMID- 9557025
TI  - [Connection between 2 tuberculosis outbreaks demonstrated after 8 years by DNA
      fingerprinting of the causative mycobacteria].
AB  - OBJECTIVE: To determine the possible connection between two outbreaks of
      tuberculosis at an 8-year interval by DNA fingerprinting of the causative
      mycobacteria. DESIGN: Descriptive. SETTING: Regional Public Health Services
      Zeeland and Noord-Holland, the Netherlands. METHOD: The source patients of the
      tuberculosis explosions in an island in the province of Zeeland (28 persons
      infected) and an island of the Noord-Holland area (36 persons infected) were
      identified in 1986 and 1994 respectively. In 1994. spoligotyping was performed on
      dead bacteria from the suspected source from 1986. to analyse the chain of
      transmission. RESULTS: Identical spoligotyping patterns of the source patients
      proved the transmission of a Mycobacterium tuberculosis strain from a father to
      his son around 1986. Lack of a positive Mantoux test in the son prohibited
      prevention of the 1994 explosion. CONCLUSION: Thanks to the applicability of
      spoligotyping on non-vital mycobacteria this DNA method contributed
      retrospectively to demonstration of a connection between two out-breaks of
      tuberculosis at an 8-year interval.

PMID- 9557026
TI  - [Acute myocardial infarct following sulprostone administration].
AB  - Because of intrauterine foetal death at 35 weeks, parturition in a woman aged 35
      years was induced by intravenous sulprostone. A few hours after its start she
      sustained a myocardial infarction for which she was treated. Coronary angiography
      4 weeks later showed normal coronary arteries and good left ventricular function.
      Mild cardiovascular reactions such as bradycardia and mild hypotension are
      frequently observed adverse effects. In some instances, sulprostone can induce
      myocardial ischaemia. However, the possibility of a myocardial infarction is not
      mentioned in the product information of sulprostone. As there was an obvious
      temporal relationship and other causative factors were sufficiently excluded, the
      causal relation between the administration of sulprostone and the occurrence of
      myocardial infarction can be regarded as almost certain. Several experimental
      studies provide support for the hypothesis that coronary spasms play a major role
      in the pathophysiology of a myocardial infarction during the administration of
      sulprostone.

PMID- 9557027
TI  - [Circulatory arrest following sulprostone administration in postpartum
      hemorrhage].
AB  - In a woman aged 39 cardiac arrest occurred 3.5 hours after administration of 250
      micrograms sulprostone directly into the uterine wall for a post-partum
      haemorrhage after manual removal of the placenta. A long period of resuscitation
      was necessary. After further evaluation the woman demonstrated specific
      contraindications to the administration of sulprostone. as formulated by the
      French authorities: age > 35 years, heavy cigarette smoking, and cardiovascular
      risk factors. In the Netherlands sulprostone is registered for intravenous
      administration only. We would strongly advise against administration directly
      into the uterine wall.

PMID- 9557028
TI  - [Cost-effectiveness of pneumococcal vaccination of the elderly].

PMID- 9557029
TI  - [Cost-effectiveness of pneumococcal vaccination in the elderly].

PMID- 9557030
TI  - [Residents not-in-training and hospital physicians: pariahs in the hospital].

PMID- 9557031
TI  - [Hospital mortality and survival following partial pancreaticoduodenectomy].

PMID- 9557033
TI  - [What are the consequences of the new American guidelines for the diagnosis of
      diabetes mellitus in The Netherlands?].
AB  - The American Diabetes Association (ADA) recently issued new guidelines for
      classification and diagnosis of diabetes mellitus. The main change is the
      decrease of the liminal value of the fasting plasma glucose level from 7.8 to 7.0
      mmol/l. A fasting level of 6.1-6.9 mmol/l indicates impaired glucose tolerance
      (which eliminates the category 'impaired glucose tolerance', which was
      established on the basis of a slightly increased 2-hour glucose level after
      ingestion of 75 g glucose). Consequently, the ADA criteria render the oral
      glucose tolerance test (GTT) redundant for clinical practice. Given these
      criteria, the prevalence of diabetes mellitus among the general Dutch population
      will change only slightly, but the number of persons to be classified in a
      different category after their introduction is considerable: 39.2% of the ADA
      diabetics are not diabetics according to the current WHO classification, while
      38.1% of the WHO diabetics are not diabetics according to the ADA criteria. The
      criteria established by the ADA accommodate clinical practice, in which the GTT
      is hardly used anymore. The WHO still has to decide about whether or not
      accepting the ADA guidelines.

PMID- 9557032
TI  - [Old, short-of-breath and confused; delirium as a manifestation of pulmonary
      embolism in geriatric patients].
AB  - Two women aged 88 and 70 and a man aged 90 years had become increasingly confused
      and short of breath over a period of a few weeks. Blood gas analysis revealed
      serious hypoxia. For lack of an explanation of the respiratory insufficiency,
      pulmonary emboli were assumed; this assumption could be confirmed by ventilation
      perfusion scintigraphy. Parallel with the treatment of the emboli the delirium
      cleared. Because of restlessness, initial treatment with low molecular weight
      heparin subcutaneously twice daily was preferred.

PMID- 9557034
TI  - [Diabetes mellitus: current classification based on cause and sharpened blood
      glucose limits for diagnosis].
AB  - Recently new definitions were agreed for the glucose tolerance test (GTT), for
      impaired glucose tolerance and for the classification of diabetes mellitus. The
      World Health Organization and the American Diabetes Association have been active
      on this point. The fasting glucose value has been lowered and been brought into
      line with the two hour value of the GTT. Fasting glucose values can now be used
      for the diagnosis of diabetes mellitus and of impaired glucose tolerance. The new
      classification is based on differences in cause of the diabetes. The
      classification includes diabetes mellitus types 1 and 2, pregnancy diabetes and
      'other forms of diabetes'.

PMID- 9557035
TI  - [A new subtype of diabetes mellitus: maternally inherited diabetes and deafness
      (MIDD)].
AB  - Diabetes mellitus comprises many subtypes, the pathogenesis of each of which
      involves a combination of inherited and environmental factors. Recently a new
      subtype of diabetes mellitus was recognized in a Dutch pedigree, designated as
      'maternally inherited diabetes and deafness' (MIDD). Impaired hearing is an
      associated phenomenon of the disease. Approximately 1.3% of all diabetic cases in
      the Netherlands exhibit the MIDD subtype. MIDD shows a strictly maternal
      heredity. In MIDD there is a guanine-for-adenine substitution at position 3243 in
      mitochondrial DNA. Mitochondria carrying this mutation exhibit a decreased
      functionality. In carriers of the MIDD mutation the insulin secretion by the
      pancreas in response to stimulation by glucose is impaired.

PMID- 9557036
TI  - [From absenteeism to work incapacity; changed role of physicians involved].
AB  - Hardly any part of the legal regulations on absenteeism and incapacity for work
      has remained unchanged since 1993 in the Netherlands. The system is becoming
      increasingly complicated. The essence of the changes is that employers'
      responsibility has greatly increased. The new regulations mean a transition from
      industrial health care to Factories Act services and from the industrial
      insurance board to implementing organs. The legislator emphasizes the evaluation
      of what people with health disorders are still able to do. Prevention of
      absenteeism/ incapacity for work and reintegration are given great attention.
      Treating physicians should not let the complicated regulations keep them from
      fulfilling their tasks concerning sick employees, since it is increasingly in the
      patient's interest that chronicity be prevented whenever possible.

PMID- 9557037
TI  - [The Montignac method: scientific foundation debatable].
AB  - Obesity is a major health issue in Western society. In the Netherlands every
      fifth person suffers from obesity and every third person is on a weight-reducing
      diet. The Montignac method is a very popular diet. The diet is claimed to be a
      nutritional science. The method is based on several hypotheses about the
      metabolism of carbohydrates and fatty acids: carbohydrates with a low glycaemic
      index are preferred, carbohydrates are not to be eaten in combination with fatty
      acids, fruit is propagated but must not be combined with other components. The
      scientific literature refutes the hypotheses of Montignac regarding the metabolic
      effects of carbohydrates and fatty acids. As a method to lose weight, the
      conventional recommendations of caloric restriction, less intake of saturated
      fatty acids and more physical activity should be preferred to the Montignac diet.

PMID- 9557038
TI  - [Diagnosis and treatment of hypertension prior to and following introduction of a
      protocol].
AB  - OBJECTIVE: To determine the compliance with and the outcome of a practice
      guideline introduced for the management of hypertension. DESIGN: Retrospective
      medical record survey. SETTING: The outpatient clinic of general internal
      medicine of the Academic Medical Hospital Nijmegen, the Netherlands. METHOD:
      Daily practice in a period before (1988) and one after (1993) implementation of
      the guideline were compared. By means of an inventory form we evaluated the
      compliance with the guideline, the decrease in blood pressure after 1 year's
      follow-up and the number and dosages of the prescribed drugs. Total costs were
      approximated from the number of visits and the number of laboratory and imaging
      evaluations. RESULTS: Compliance with the guideline in 1993 was 72% (24) compared
      with 65% (27) in 1988. This improvement was predominantly achieved by the junior
      residents. In 1993 in 15 patients (19%) blood pressure was measured without
      medication having been stopped. The guideline regarding the frequency of blood
      pressure measurement was observed in 7 patients (9%). The decrease in systolic
      and diastolic blood pressure was larger in 1993 than in 1988 (p < 0.05). This
      result was achieved by a larger number of blood pressure lowering drugs (1.40
      (1.06) in 1993 vs. 1.17 (0.98) in 1988): the mean dose of the prescribed drugs
      was lower. The number of visits rose by 10% to 7.8 (3.7) and the number of
      diagnostic laboratory procedures by 25% to 956.

PMID- 9557039
TI  - [Percutaneous jugular Tesio catheter useful for long-term hemodialysis:
      experiences in 26 patients].
AB  - OBJECTIVE: Inventory of the Tesio catheter (TC), its functioning and
      complications. DESIGN: Retrospective descriptive file investigation. SETTING:
      Rijnstate Hospital, Arnhem, the Netherlands. METHOD: From the hospital files of
      the patients with chronic renal insufficiency who from July 1992 until October
      1995 received a TC, we collected data on indications for placing and removing,
      duration, complications of the TC and mortality. RESULTS: Data were suitable for
      26 patients, 8 men and 18 women, mean age 63 year (range: 33-79). The indications
      proved to be short life expectancy, failure of other vascular access and expected
      long catheter dialysis. The total number of days the TC was in situ was 2780
      (median: 80.5: range: 15-559). Fourteen patients showed no complications, one
      patient had dysfunction of the TC due to thrombosis, local infection occurred
      around the insertion opening in five and bacteremia in seven patients. In one
      patient, with a prosthetic cardiac valve, the catheter had to be removed
      prematurely because of an infection. No deaths due to the TC occurred.
      CONCLUSION: The TC appears to be a safe form for long-term haemodialysis.

PMID- 9557040
TI  - [Isolated traumatic dorsal dislocation of the metacarpophalangeal joint of the
      index finger].
AB  - A woman aged 36 sustained a dislocation of the metacarpophalangeal joint of the
      index finger occurred during a volleyball match. It appeared to be a complex
      dislocation with entrapment of soft tissue, which is rare. Open reduction with a
      volar approach gave a good result. The postoperative course was uneventful.
      Adequate treatment necessitates rapid diagnosis. The herniation of the head of
      the metacarpal bone through the volar surface precluded closed repositioning. The
      palmar surgical approach is difficult but gives good anatomical results. The
      dorsal approach is safer but more laborious. Rapid mobilization is necessary for
      a good long-term result.

PMID- 9557041
TI  - [Clostridium difficile outbreak in surgical wards].
AB  - OBJECTIVE: To evaluate the clinical consequences of a hospital outbreak of
      Clostridium difficile infections in the Netherlands. DESIGN: Descriptive.
      SETTING: Diakonessen Hospital Utrecht, the Netherlands. METHODS: In the period
      from 1 August 1995 to 1 September 1996 C. difficile infections were recorded
      (gastrointestinal symptoms after use of antibiotics and findings at C. difficile
      toxin assay in faeces, or sigmoidoscopy). The monthly incidence of infections
      increased to 5 patients in December 1995; at that time strict hygienic measures
      were implemented and perioperative antimicrobial prophylaxis was adjusted. Data
      on the clinical course were collected retrospectively from the records of the
      patients involved. RESULTS: In 20 patients, admitted for various reasons to the
      surgical wards, hospital stay was complicated by a C. difficile infection. The
      mean age was 70 years. Eleven patients presented with diarrhoea, eight patients
      had nausea and vomiting as well. Diagnosis was confirmed by C. difficile toxin
      determination in most patients (n = 15). Despite antibiotic treatment in 19
      patients, recurrences were seen in five patients (25%) and five patients died
      (25%). The monthly incidence declined to 0-1 per month. CONCLUSION: C. difficile
      infections in surgical patients carry a significant morbidity and mortality.
      Preventive hygienic measures are important to control spread of the infection.

PMID- 9557042
TI  - [The relationship between health gain and effort in mass screening for breast
      cancer].

PMID- 9557043
TI  - [Heart tamponade: a life-threatening complication of a central venous catheter].

PMID- 9557044
TI  - [Future developments in heredity research. I. Technological possibilities].

PMID- 9557045
TI  - [Rhinologic changes in cystic fibrosis and hypogammaglobulinemia].
AB  - Nasal and paranasal findings in cystic fibrosis and hypogammaglobulinaemia are
      presented. Two cases are discussed. Case one that is 20 year old man with
      oedemato-polypoid changes of nasal mucosa and diagnosis of cystic fibrosis was
      made during his staying in hospital. Case 2 that is 12 year old boy with
      previously diagnosed hypogammaglobulinaemia also presented oedemato-polypoid
      changes of nasal mucosa. Both pharmacological and surgical treatments were
      brought. Authors' observations are compared with the literature and necessity of
      detailed diagnosis of oedemato-polypoid changes of nasal and paranasal sinus'
      mucosa is stressed.

PMID- 9557046
TI  - [Treatment of bilateral vocal cord paralysis: surgical technique and functional
      results].
AB  - The authors present possibilities of the surgical treatment in bilateral vocal
      cord paralysis. We described the technique of the operation which is being used
      in our department in such a cases. 13 patients were analyzed after operations (11
      women, 2 men). Bilateral vocal cord paralysis was caused by thyroidectomy (11
      cases), virus infection (1 case) and in the course of multiple sclerosis (1
      case). Functional results were evaluated by subjective examination, indirect
      laryngoscopy, spirometry and video-laryngoscopy. The effects of the treatment
      were satisfied.

PMID- 9557047
TI  - [Mucocele of the paranasal sinuses].
AB  - Twelve cases selected from the group of 123 chronic rhinosinusitis patients are
      presented in the paper. Severe headaches were noted as the most typical
      complaints of the clinical picture of the disease. The most cases were
      accompanied by rhinitis and paranasal sinusitis symptoms. The best diagnostic
      method of mucocele is MRI. The endoscopic sinus surgery is a safe and effective
      method of the treatment in a case of mucocele.

PMID- 9557048
TI  - [The effect of nitrous oxide on middle ear pressure in secretory otitis media in
      children].
AB  - The preliminary results of the nitrous oxide application during children
      anesthesia with secretory otitis media was presented. The different otological
      operations in which nitrous oxide is contraindicated were mentioned. The nitrous
      oxide influence on the middle ear pressure increase was emphasized. It was
      confirmed by tympanograms. Necessity of the further investigations in this
      subject were emphasized due to encouraging results.

PMID- 9557049
TI  - [Ultrasonographic characteristics of neck lesions and the value of ultrasound
      examination in postoperative monitoring of patients with laryngeal cancer].
AB  - The purpose of this study was to evaluate the superiority of ultrasound
      examination of the neck in comparison with palpation in patients operated on and
      irradiated because of the larynx cancer. Close follow up by means of
      ultrasonography all patients after initial operation is essential to detect
      recurrence early, while surgical salvage is still feasible. Scars, oedema and
      anatomical changes due to prior surgery and radiotherapy make the clinical
      examination very difficult. Apart from demonstrating non palpable nodes,
      ultrasound may also depict nodal size, multiplicity, relation to the surrounding
      vessels, invasion of the carotid artery and malignant extension in the salivary
      glands or thyroid. 12 pictures of ultrasound were presented.

PMID- 9557050
TI  - [Use of mucolytic preparations (Mucosolvan) in selected diseases of the upper
      respiratory tract. Part II].
AB  - The majority of publications in the recent years emphasizes the importance of
      mucolytic preparations in the upper respiratory tract diseases. There have been
      very few report about the important role which mucolytic drugs may play in the
      diseases of the upper respiratory tract. This paper undertakes the task of
      attempting to evaluate the usefulness of Mucosolvan preparation in laryngological
      diseases. The main condition of the successful treatment of otolaryngological
      diseases is maintaining the efficient mechanism of the clearing of upper
      respiratory tract. This is achieved by means of the mucocilia apparatus, namely
      cilia and mucosa protecting the epithelium from harmful factors. Tests were
      carried out on 60 patients with paranasal sinuses and ear diseases. The first
      group comprised 45 patients who were qualified on the basis of inflammatory
      changes in paranasal sinuses. The second group comprised 12 children and 3 adults
      with otitis media with effusion. Mucosolvan which was used in the supplementary
      treatment fulfilled our expectations. The use of the mucolytic drug accelerated
      the healing process, proper regeneration of the epithelium and the reduction of
      the period of drug administration.

PMID- 9557051
TI  - [The possibility of tinnitus suppression by electrical stimulation].
AB  - The authors described the treatment of 36 patients with persistent tinnitus. In
      the past the patients were treated with other methods without positive results.
      After audiological examinations Promontory Stimulator (Cochlear Co.) for
      electrical stimulation was used. During the electrical stimulation one electrode
      was inserted in external auditory meatus and the other on planum mastoideum.
      Bursts of biphasic pulses of 0.1 ms duration were used during electrical
      stimulation. Electrical stimulation was applied 10 min. during 10 days. The
      patients estimated effects of treatment and results are presented in table. The
      authors obtained satisfactory results in 48% of the patients.

PMID- 9557052
TI  - [The sixtieth anniversary of Miodonski's paraboloid head lamp reflector].
AB  - On the 60th anniversary of the elaboration by Miodonski of the optical solutions
      and his construction of the Paraboloid Headlamp and its application to clinical
      practice, the author compares its characteristics with other types of lamp used
      in otolaryngology on the example of Clar's Headlamp and Headmirror. This
      comparison shows that even now Miodonski's Paraboloid Headlamp due to its
      qualities, has no equal. The merits of Miodonski's Headlamp are as follows: 1.
      Permits a change of the axis of illumination under sterile condition; 2. Gives
      the most powerful light; 3. Permits binocular inspection of very narrow and long
      canals and ducts allowing for enlargement from the time that Miodonski added a
      magnifying and mobilizing lens to his headlamp in 1961.

PMID- 9557053
TI  - [Basic principles of LIFE--autofluorescence bronchoscopy. Results of 194
      examinations in comparison with standard procedures for early detection of
      bronchial carcinoma--overview].
AB  - BACKGROUND: Conventional bronchoscopy in the identification of preneoplasias and
      carcinoma in situ (CIS) has been inadequate to date. Tissue autofluorescence was
      found to differentiate normal mucosa from dysplastic or carcinomatous bronchial
      mucosa. This principle resulted in the development of the LIFE System (Light
      Imaging Fluorescence Endoscope, Xillix Techn., Vancouver, BC), now in routine use
      worldwide at 35 centres. In a prospective multicentric study in North America the
      relative sensitivity for diagnosing intraepithelial neoplasias of combined white
      light (WLB) and LIFE bronchoscopy in 173 at-risk patients was 6.3 as compared to
      WLB alone. A similar European multicentric study will be completed by spring of
      1998. PATIENTS AND RESULTS: We report on our experience with the routine use of
      the LIFE System over 23 months. 194 examinations (165 patients) were performed.
      Moderate to severe dysplasias and in situ carcinomas were diagnosed with a
      relative sensitivity of 2.7 by the combined WLB-LIFE examination as compared to
      WLB alone. CONCLUSION: Autofluorescence bronchoscopy as a routine investigation
      without need of photosensitizers in patients with a high risk for lung cancer can
      lead to a substantial increase in the detection rate of CIS and moderate to
      severe dysplasias compared to white light bronchoscopy alone.

PMID- 9557054
TI  - [Current indications for resection of tuberculoid lung changes--relics of the pre
      chemotherapy era?].
AB  - The spectrum of indications for elective resection of pulmonary tuberculosis was
      considerably reduced by clinical evaluation of the effective antituberculous
      chemotherapy and is limited only to a few pathomorphological processes and
      clinical situations today. The same estimation is valid in case of nontuberculous
      mycobacteriosis with clinical importance. The combined therapy with new macrolid
      antibiotics, quinoloses and Rifampicin-derivatives current enlarged the options
      of conservative therapy. Thus the surgery of pulmonary tuberculosis are rare
      operations and are essentially limited to the therapy of late complications of a
      former collapse therapy, of destroyed lungs and bronchiectasis with recurrent
      infect exacerbations and life threatening or massive recurrent haemoptysis.

PMID- 9557055
TI  - [Nosocomial ventilator-associated pneumonias caused by Aspergillus fumigatus in
      non-immunosuppressed, non-neutropenic patients].
AB  - We observed three cases of severe ventilator-associated pneumonia due to
      Aspergillus fumigatus in non-immunosuppressed, non-neutropenic patients. Autopsy
      confirmed an angioinvasive pattern of spreading with septic foci. In all cases
      conditions associated with temporary immunodysfunction like underlying diseases,
      antecedent sepsis or pneumonia, coinfections or steroid therapy were present.
      Although Aspergillus fumigatus was isolated in all cases in cultures of
      tracheobronchial secretions, the correct diagnosis was not obtained during
      lifetime. Our cases demonstrate that pneumonia due to Aspergillus fumigatus must
      be taken into account also in this patient population.

PMID- 9557056
TI  - [Rapid prediction of rifampin susceptibility of Mycobacterium tuberculosis].

PMID- 9557057
TI  - [DNA fingerprints of Mycobacterium tuberculosis isolates of patients confined for
      therapy noncompliance show frequent clustering].

PMID- 9557058
TI  - [Comparison of anterior rhinomanometry and impulse oscillometry in nasal
      provocation with histamine].
AB  - Anterior rhinomanometry (aR) is the standard method for measurement of nasal
      resistance, but it has some drawbacks because it requires full co-operation of
      the patient and the results are disturbed by forced ventilation due to stenosis.
      The patient must generate flow by active ventilation. Resistance results from the
      flow/pressure ratio. Forced oscillation technique (IOS) does not affect
      spontaneous breathing. Flow/pressure ratio is generated externally by a
      loudspeaker. IOS measures not only resistance but also reactance. Whereas former
      methods used only a single frequency IOS is capable of applying and analysing
      frequencies between 0 and 100 Hz. The range from 5 to 35 Hz is useful for
      diagnostic issues. We compared IOS with aR in nasal provocation tests with
      histamine and checked the sensitivity of resistance (R) and reactance (X) at
      different frequencies. METHOD: 20 patients (13 m, 7 f) underwent nasal challenge
      test using increasing doses of histamine (max. 3.2 mg). Resistance (aR, IOS) and
      reactance (IOS) were measured parallel. To compare the two methods, we calculated
      the dose of histamine which is required to double nasal resistance. RESULTS: 1.
      IOS demonstrates the increase of R at all frequencies. 2. The highest increase of
      R is measured at a frequency of 5 Hz (5 Hz: NaCl 0.41 +/- 0.25; Hist. 1.26 +/-
      0.57; 35 Hz: NaCl 0.36 +/- 0.172; Hist. 0.60 +/- 0.1 kPa/l/s, p < 0.001). 3. The
      critical dose is significantly lower in IOS than in aR (2.29 +/- 2.59 vs. 1.06 +/
      1.16 mg/ml, p < 0.02). 4. Basal values of R do not differ significantly between
      aR and IOS (0.37 +/- 0.12 vs. 0.41 +/- 0.25 kPa/l/s, p < 0.001). CONCLUSIONS: We
      conclude from our results that IOS is at least equivalent to aR in measuring
      nasal resistance. R at 5 Hz is the most important parameter in IOS. IOS is less
      dependent on the cooperation of the patient. In case of stenosis it does not
      require forced ventilation to achieve the required flow-pressure ratio.

PMID- 9557059
TI  - [Diagnostic value of somatostatin receptor scintigraphy with indium-111
      pentetreotide in small-cell bronchial carcinoma].
AB  - Small-cell lung cancer (SCLC) cells may express somatostatin receptors [14].
      Receptor-positive tissue can be visualised in vivo by scintigraphy with
      radiolabelled somatostatin analogues. In a prospective study we examined 18
      patients with histologically proven SCLC for the diagnostic value of somatostatin
      receptor scintigraphy using indium-111 pentetreotide. Planar whole body scanning
      was performed 4 and 24 hours after administration. Additional SPECT imaging of
      the thorax and the abdomen was done at 24 hours. The results were compared with
      conventional staging procedures: ultrasound, x-ray, computed tomography and bone
      scintigraphy. In all 18 patients the primary tumour was correctly identified. Out
      of 13 patients with mediastinal lymphoma formation 10 patients showed positive
      SRS. In 2 more patients SRS showed mediastinal uptake while CT scanning was
      negative. The detection of distant metastases in patients with extensive disease
      was true positive in 8 cases (OSS, HEP, BRA), false negative in 4 cases (PLE,
      ADR, HEP), corresponding to a sensitivity of 67%. In 2 patients cerebral
      metastases were no longer detectable by SRS after previous local irradiation.
      Even though the method is limited in respect of revealing distant metastases in
      the upper abdominal area due to physiological uptake in liver, spleen and
      kidneys, differentiation between limited disease (LD) and extensive disease (ED)
      was possible in all cases. We conclude that [111In]pentetreotide scintigraphy is
      a suitable method for the detection of SCLC primary tumours and a substantial
      tool for differentiation between LD and ED if combined with ultrasonography of
      the upper abdomen.

PMID- 9557060
TI  - [Surgery of late complications of previous active treatment of lung tuberculosis
      with extrapleural plombage].
AB  - Between January 1984 and February 1997 10 patients with late complications of a
      former active collapse therapy were operated. In case of our patients between
      1943 and 1960 the collaps therapy was carried out with the extrapleural
      instillation of plombs for therapy of pulmonary tuberculosis. At present main
      complications were infections of plombs with pleurobronchial and pleurocutaneus
      fistulas and perforation of plombs. By all patients both extirpation and
      pleurectomy were necessary. In case of 5 patients additionally lung resection was
      required, in case of 3 patients a thoracoplasty and by 1 patient a myoplasty.
      Although there are considerable destructions of lung parenchym in a part the
      results of long-term follow up are satisfactory: 6 patients are so far without
      complaints; only 1 patient died 10 years postoperative. Prerequisite for a
      successful therapy are the knowledge of the surgical methods of the collaps area,
      the used materials, the pathomorphological pulmonary changes and the good
      cooperation between pneumologists and thoracic surgeons.

PMID- 9557061
TI  - Hypermobility syndrome.

PMID- 9557063
TI  - Postpartum psychiatric illness: the role of the pediatrician.
AB  - PPD occurs in 10% to 20% of postpartum women. Maternal depression can affect a
      child's development significantly. Pediatricians can screen for maternal
      psychiatric illness with little effort; of all the health care professionals,
      they may be in the best position to do so. Pediatricians can help affected
      mothers obtain appropriate treatment and help mobilize social resources. This
      simple process can minimize morbidity to pediatric patients.

PMID- 9557062
TI  - Cephalosporins: an update.
AB  - The cephalosporins are the largest and most diverse family of antimicrobial
      agents available. Although they rarely are considered drugs of first choice for
      the therapy of bacterial infections, they are the most commonly prescribed agents
      for both ambulatory and hospitalized patients. The first-generation agents have
      the most limited spectrum of bactericidal activity, but they are the most potent
      against Gram-positive microbes. The third- and fourth-generation agents have a
      broad spectrum of activity that includes the majority of Gram-negative pathogens.
      However, they are less active than their first-generation counterparts against
      Gram-positive bacteria, especially S aureus. The cephalosporins generally are
      well tolerated, and the oral agents are palatable. However, their use is limited
      by increasing resistance among certain groups of bacteria and high cost,
      especially of the parenteral and recently licensed oral agents. The prudent
      physician need not be familiar with all cephalosporins, but should be
      knowledgeable about a select few.

PMID- 9557064
TI  - Diagnosis and management of headache in children.

PMID- 9557065
TI  - Index of suspicion. Case 1. Diagnosis: infectious mononucleosis.

PMID- 9557066
TI  - Index of suspicion. Case 2. Diagnosis: recurrent bacterial meningitis.

PMID- 9557067
TI  - Index of suspicion. Case 3. Diagnosis: glucose-6-phosphate dehydrogenase
      deficiency.

PMID- 9557068
TI  - Erythromycin.

PMID- 9557069
TI  - Nasal septal hematoma.
AB  - Nasal septal hematoma is a rare but potentially serious complication of nasal
      trauma. Proper management consists of early recognition, prompt surgical
      evacuation of the hematoma, and antimicrobial therapy if a secondary nasal septal
      abscess is suspected. Clindamycin is recommended as initial therapy until the
      results of cultures and susceptibility studies are available.

PMID- 9557070
TI  - [Influenza and its prophylaxis].

PMID- 9557071
TI  - [Evaluation of electrophysiologic properties of the heart atrium in patients with
      electrically induced atrial fibrillation].
AB  - Paroxysmal palpitation is a frequent non-specific symptom observed in clinical
      practice. It is not always possible to identify the arrhythmogenic cause of this
      complaint. The induction of paroxysmal atrial fibrillation (PAF) during
      transoesophageal pacing (TEP) was found to be particularly useful when arrhythmia
      paroxysms were not evidenced by standard electrocardiography or by 24-hour Holter
      monitoring. The objective of the present study was a comparative assessment of
      the electrophysiological parameters obtained from a patient group with PAF
      induced during TEP and from a patient group with no arrhythmia, in order to
      determine the hazard of spontaneous PAF occurrence. The study included 116
      patients complaining of palpitations who underwent TEP. Of these, 53 were
      selected (34 males and 19 females; mean age, 47.6 +/- 13.1) in whom a sustained
      PAF episode (> 30 sec) had been induced during TEP. These patients are referred
      to Group I. Group II (control) comprised the remaining 63 patients (38 males and
      25 females; mean age 45.5 +/- 8.5) in whom no PAF episode had been induced during
      TEP. All patients (Group I and Group II) underwent echocardiography, 24-hour
      Holter monitoring, exercise test and TEP. During TEP the following parameters
      were evaluated: left atrial effective refractory period (AERP), sinoatrial
      conduction time (SACT), maximal and corrected sinus node recovery time (SNRT and
      CNRT), Wenckebach periodicity (WP) and mean cycle duration (CD). Thus, the AERP
      value amounted to 299.8 +/- 42.4 msec and 259.5 +/- 54.9 msec (p < 0.001) for
      Group I and Group II, respectively. The SACT and SNRT values totalled 132.3 +/-
      45.1 msec and 1011.1 +/- 165.6 msec in Group I, and 103.2 +/- 29.9 msec and 838.3
      +/- 172.7 msec in Group II, respectively (p < 0.001). Compared to the control
      (235 +/- 95.7 msec; 200.3 +/- 64.9 msec, respectively), the group of patients
      with electrically-induced PAF (Group I) showed significantly longer CNRT (383.4
      +/- 172.5 msec, p < 0.001) and WP (350.8 +/- 59.3 msec, p < 0.001). The study had
      led to the following finding: patients with electrically-induced PAF had
      significantly longer left effective refractory periods, sinoatrial conduction
      times, maximal and corrected sinus node recovery times and Wenckebach
      periodicities.

PMID- 9557072
TI  - [Activity of cathepsin B and collagenase in urine and excretion of fibronectin
      and TGF-beta 1 in urine of patients with membranous glomerulonephritis].
AB  - In 30% cases nephrotic syndrome is due to membranous glomerulonephritis (MG).
      Fifty percent of patients reveal end stage renal disease in 15 years follow-up.
      The another 50% gain persistent remission. The pathogenesis of disease is not
      known. Protein accumulation in glomeruli leads to progressive loss of kidney
      structure and function in MG. Also the role of tissue proteolytic systems and
      growth factors in this process is not known. We aimed to estimate urine cathepsin
      B, collagenase activity and urine excretion of TGF-beta 1 and fibronectin in MG.
      MG patients revealed increased urine cathepsin B activity (10.58 +/- 8.73 pmol
      AMC/mg creatinine/min. vs. control 7.11 +/- 2.05 pmol AMC/mg creatinine/min. [p <
      0.05]), urine collagenase activity (8.59 +/- 4.26 pmol AMC/mg creatinine/min. vs.
      control 3.84 +/- 2.09 pmol AMC/mg creatinine/min. [p > 0.02]) and increased urine
      excretion of fibronectin (214 +/- 335 ng/mg creatinine vs. control 12.7 +/- 6.7
      ng/mg creatinine [p < 0.05]) and increased urine excretion of TGF-beta 1 (283.55
      +/- 248.13 pg/ml vs. control 36.11 +/- 48.01 pg/ml [p < 0.05]). The results
      indicates on glomerular overproduction of TGF-beta 1 and urinary leak of
      proteolytic enzymes which may exacerbate glomerular proteolytic activity in MG.
      This may lead to glomerular protein accumulation and progressive loss of kidney
      function and structure in MG. Increased urine fibronectin excretion in MG
      patients seems to confirm the hypothesis.

PMID- 9557073
TI  - [Cognitive function in patients with systemic sclerosis].
AB  - Central nervous system involvement is seldom reported in patients with systemic
      sclerosis (SSc). Cognitive functions were determined in 21 patients with definite
      SSc and 42 healthy controls. Thyroid function was also measured in order to
      eliminate the effect of hypothyroidism on cognitive functioning. It was found
      that the SSc patients with normal thyroid function showed defective long-term and
      recent memory, learning ability, criticism, perception and visuo-perceptual
      skills, their simple reaction time was prolonged. Similar but less advanced
      cognitive defects were shown in the SSc patients with overt or latent
      hypothyroidism. The obtained results indicate that the central nervous system
      involvement is more common in patients with SSc than it has been reported
      earlier.

PMID- 9557074
TI  - [Risk factors for atherosclerosis in offspring of parents with primary
      hypertriglyceridemia].
AB  - High triglycerides and low fibrinolysis activity are considered as a significant
      predictors for atherosclerosis. The aim of our study was: 1-to compare these risk
      factors levels in children with positive family history of hypertriglyceridemia
      (HTG) with children from healthy families and 2-to assess the association between
      triglyceride and fibrinolysis activity in offspring (y) and parental risk factors
      (xl ... xn) for atherosclerosis. The study population consisted of: I Group 15
      children 7-12 years old and their parents from HTG families and II Group 26
      control children 5-12 years old from healthy families. Triglyceride (TG), total
      cholesterol, cholesterol esters, LDL-Ch, HDL-Ch, HDL2Ch, apolipoprotein AI and
      BII, fibrinogen plasma level were determined. Plasminogen activator inhibitor
      (PAI-1) and fibrinolysis activity and (ELT) were determined. We found significant
      differences in clinical examinations (higher blood pressure and ECG disturbances
      more frequently), HDL-Ch and HDL2-Ch plasma level was lower in children with
      positive family history than in control children. Multiple regression analysis of
      parental variables demonstrated, that children's TG and ELT are strongly
      determined by parental lipids and haemostasis parameters in children with
      positive family history of HTG.

PMID- 9557075
TI  - [Case report presentation for treatment of pure red cell aplasia].
AB  - We presented a case of a 34 year old male patient with pure red cell aplasia. He
      was treated with antithymocyte globulin (Pasteur Merieux, France) at a dose of
      175 mg in 350 ml 0.9% NaCl in intravenous drip infusion--10 drip/min for 5
      consecutive days. The therapy resulted in normalization of morphological
      parameters. Patient was under clinical observation. After 9 years when hemoglobin
      level decreased monoclonal antibody OKT3 og IgG 2a type (Cilag Ag International,
      Switzerland) at a dose of 5 mg intravenous for 10 consecutive days was applied.
      During the first and second therapy course symptoms of serum sickness and "flu
      like" syndrome was observed. The results of the two treatment appeared positive.
      We received normalization of morphological parameters.

PMID- 9557076
TI  - [Distal tubular acidosis in a patient with insulin dependent diabetes mellitus-
      selected pathophysiologic, diagnostic and therapeutic aspects].
AB  - This case report describes a 42 years old male patients with distal tubular renal
      acidosis in whom the symptomatology of this disorder was markedly changed by the
      presence of concomitant endocrine and exocrine insufficiency of the pancreas.
      Pathophysiological, diagnostic and therapeutic aspects of coexistence of these
      two type of pathology are stressed.

PMID- 9557077
TI  - [Adrenomedullin].

PMID- 9557079
TI  - [Video-thoracoscopy in thoracic diseases].

PMID- 9557078
TI  - [The role of eosinophils in inflammation].

PMID- 9557080
TI  - [Clinical use of thrombopoietin--hypotheses and clinical promises].

PMID- 9557081
TI  - [Hemodialysis yesterday and today].

PMID- 9557083
TI  - [Progress in diagnosis and treatment of glomerulopathies].

PMID- 9557082
TI  - [Kidney transplantation in Warsaw and Poland in the years 1966-1996].

PMID- 9557084
TI  - [The role of mesangial matrix in kidney diseases].

PMID- 9557085
TI  - [Recurrence of primary glomerulopathy in children after kidney transplantation].

PMID- 9557086
TI  - Cancer in endstage renal failure: potential pathogenic factors.

PMID- 9557087
TI  - [Metabolism of magnesium and lipid disturbances in chronic renal failure].

PMID- 9557088
TI  - [Function of the left heart atrium during hemodialysis].
AB  - In 23 chronic uremic patients effect of four-hour hemodialysis on function the
      left atrium of the heart was investigated. The reference group consisted of 17
      healthy subjects. The function was evaluated by cross-sectional Doppler
      echocardiography. Before hemodialysis maximal (LAmax) and minimal (LAmin) left
      atrial dimensions and left atrial dimension obtained in M-mode of long axis in
      parasternal projection (LAa), pre-ejection period (PEPlp), ejection time (ETlp),
      PEPlo/ETlp ratio and left atrial fiber shortening fraction (FS%lp) were
      significantly higher in chronic uremic patients than those found in healthy
      subjects. Four-hour hemodialysis induced decreases in these indices, but only a
      lowering of LAa, PEPlp/ETlp ratio was statistically significant in comparison
      with pre-dialysis period. No correlation was found between changes of the
      investigated indices of the left atrial function and body weight loss during
      hemodialysis.

PMID- 9557089
TI  - [Progress in clinical diagnosis of urinary tract infection in adults].

PMID- 9557090
TI  - [Evaluation of the treatment efficacy of secondary hyperparathyroidism with oral
      pulse doses of alphacalcidol].
AB  - The purpose of the study was to evaluate the effectiveness of the oral pulse
      therapy with high doses of alphacalcidol (1 alpha(OH)D3) in secondary
      hyperparathyroidism. 16 hemodialysis patients with 4 to 9-fold iPTH serum
      elevation were given ones in week oral 1 alpha(OH)D3 in doses from 5.0 to 7.0
      micrograms (0.1 microgram/b.m.) according to serum levels of calcium, phosphate,
      activity of alkaline phosphatase with its bone fraction. Serum iPTH levels were
      measured every 3rd month of the treatment. The dialysate calcium was reduced to
      1.25 mmol/l. CaCO3 was used as a main phosphate binder in doses from 3.0 to 9.0
      g/day. After first three months of treatment the serum iPTH levels decreased from
      486.0 +/- 200 pg/ml to 218.0 +/- 117 pg/ml (p = 0.0001). Calcium levels increased
      from 2.39 +/- 0.2 mmol/l to 2.52 +/- 0.29 mmol/l (p > 0.05). Phosphate levels
      increased from 2.15 +/- 0.67 mmol/l to 2.17 +/- 0.62 mmol/l (p > 0.05). Alkaline
      phosphatase levels decreased from 35.2 +/- 17.3 IU/l to 31.1 +/- 7.78 IU/l (p >
      0.05). Bone isoenzyme of alkaline phosphatase decreased from 19.2 +/- 13.4 IU/l
      to 15.5 +/- 7.51 IU/l (p > 0.05). Because of early serum hypercalcemia, doses of
      1 alpha(OH)D3 had to be reduced in 2 patients. In 8 patients (50%) demonstrating
      decrease of serum iPTH levels (below 200 pg/ml) after first 3 months of treatment
      doses of 1 alpha(OH)D3 were reduced in the following months. We conclude that
      oral 1 alpha (OH)D3 pulse therapy is effective for parathyroid activity
      suppression in patients with severe hyperparathyroidism. To avoid dangerous
      hypercalcemia and adynamic bone disease serum iPTH and calcium levels should be
      strictly monitored.

PMID- 9557091
TI  - [Diagnosis and treatment of urinary tract infection in children].

PMID- 9557093
TI  - Our favourite drink.

PMID- 9557092
TI  - [Comparison of the clinical course of pneumonia and concentration of
      immunoglobulin in patients treated with a standard method and with the addition
      of gmma-venin P].
AB  - The therapy with immunoglobulin have been used since many years, although its
      clinical efficacy still is uncertain. The aim of this study was to compare the
      clinical course of severe pneumonia and concentration of immunoglobulin in
      patients admitted to the intensive care units (ICU). The patients were treated
      either with antibiotics only or with antibiotics and Gamma-Venin P. Investigates
      group consisted of 30 patients with severe pneumonia. 15 of them (group A) were
      treated with antibiotics only, and another 15 (group B) with antibiotics and
      Gamma-Venin P. Immunoglobulins were administrated intravenously in the maximum
      single dose 3.0 g/kg. The serum concentration of immunoglobulin were measured
      before and every second day after beginning of the treatment. 27 patients
      completed the study due to protocol (14 patients in group A and 13 patients in
      group B). Only two patients revealed sings of intolerance of Gamma-Venin P during
      the first infusion of immunoglobulin. The clinical course of pneumonia and
      duration of treatment in ICU were similar in both groups. Statistically
      significant differences in concentration of immunoglobulins in patients treated
      without immunoglobulin infusion in comparison with patients with Gamma-Venin P
      were not found. We conclude, that infusion of immunoglobulins did not improve the
      clinical course of the severe pneumonia.

PMID- 9557094
TI  - Stroke management in the decade of the brain.

PMID- 9557095
TI  - Accidental ingestions in childhood.
AB  - One-hundred and twelve cases of accidental poisoning were admitted over a 2-year
      study period (December 1990 to December 1992). Data was collected upon admission
      and patients were subsequently followed-up. Fifty-four percent of admission were
      boys. Majority of them were toddlers between the ages of 1 and 3 years. Thirty
      percent of accidental ingestions occurred during the school/public holidays.
      These occurred when the caretakers were preoccupied. Forty-nine percent of
      patients ingested oral medication; 16% ingested household liquids and the rest
      ingested other household products like cockroach tablets and thermometer mercury.
      The most commonly ingested medications were paracetamol, salicylate and
      bronchodilators, whilst chlorox, kerosene and detergents were the common
      household liquids ingested. The ability of the caregivers to quantitate the
      ingested product was poor. The mean hospital stay of the patients was 2.5 days.
      The majority of them were admitted for observation which did not require
      antidotes. Four cases were observed in the intensive care unit. There were no
      fatalities during the study period. Forty-four percent of the patients had
      samples taken for toxicology analysis, of which, less than half had positive
      results. All the patients were advised on the safety measures to look out for
      after admission. Less than 10% of cases had prior knowledge of such measures
      before the accidents occurred.

PMID- 9557096
TI  - Caesarean and postpartum hysterectomy.
AB  - AIM OF STUDY: To review the cases of caesarean and post-partum hysterectomy
      performed over a 10-year period (1986-1996) in a teaching hospital, looking
      specifically at the associated morbidity. METHOD: Retrospective review of case
      files. RESULTS: During the study period, there were 14 cases of caesarean and
      post-partum hysterectomy. Caesarean hysterectomy was performed in 0.17% of
      caesarean sections and a hysterectomy was done in 0.02% of cases following a
      vaginal delivery. Uterine atony was associated with 43% of cases. Histological
      evidence of placenta accreta or increta was noted in 7 (50%) cases, while 8 (57%)
      cases had placenta praevia. A subtotal hysterectomy was performed in 7 cases,
      where the mean operating time was significantly shorter than that in cases of
      total hysterectomy. There were no maternal deaths. Fever (28%), urinary tract
      infection (21%) and chest infection/atelectasis (21%) were the common post
      operative morbidity. Relaparotomy for continuing vaginal bleeding was required in
      2 cases. CONCLUSIONS: Emergency peri-partum hysterectomy for obstetric
      haemorrhage is a rare operation (1 in 2,550 deliveries). In spite of the intra
      operative risks and post-operative morbidity, it remains a potentially life
      saving procedure.

PMID- 9557097
TI  - Does heart rate really predict survival in septic shock?
AB  - BACKGROUND: Normalisation of heart rate after 24 hours of treatment is proposed
      to predict the survival outcome in septic shock patients. METHODS: The medical
      and surgical patients charts from 1991-1993 were selected for the diagnosis of
      septic shock (according to the definition of ACCP/SCCM Consensus Conference), and
      reviewed. Also included were patients with available variables to complete APACHE
      II and septic severity score. RESULTS: Tachycardia was observed more in the non
      survivors (9 patients) both in shock (107.8 vs 93.4) and non-shock states (112.3
      vs 93.2). Heart rate in the survival group decreased below the cut-off value,
      which is 95 beats/min, as specified by ACCP/SCCM. Comparison between APACHE II
      and SSS was not well correlated because of the small sample size. Elements in
      creating a predictor and its categorisation are mentioned. CONCLUSION: Heart rate
      was concluded to be a simple predictor reflecting physiologic derangements in
      septic shock. It is recommended that further study needs to be carried out to
      unravel a predictor of clinical value in terms of practicality, especially that
      involving the inflammatory aspect of the disease process.

PMID- 9557098
TI  - Comparing treatment response and complications between podophyllin 0.5%/0.25% in
      ethanol vs podophyllin 25% in tincture benzoin for penile warts.
AB  - AIM: The aims of this study were to: 1) ascertain if podophyllin resin in 0.5%
      [PE(0.5%)] and 0.25% [PE(0.25%)] in ethanol (PE) self-applied sequentially for 3
      days with 4 days break cycle is as effective as supervised podophyllin 25% in
      tincture benzoin (PB) applied in the clinic biweekly in treating penile warts and
      2) ascertain if PE causes less skin irritation than PB. METHODS AND RESULTS: The
      clearance rate of penile warts was 36.4% (4/11) in PE (0.5%) treated group, 66.7%
      (4/6) in the PE (0.25%) treated group and 33.3% (6/18) for PB treated group after
      1 week (ns). The wart clearance rate at 6 weeks for PE (0.5%) treated group, PE
      (0.25%) treated group and PB treated group were 81.8% (9/11), 100% (6/6) and
      83.3% (15/17) respectively (ns). There were 47 individual warts on the penis of
      the 17 patients in the PE treated group and 58 individual warts on the penis of
      the 18 patients in the PB treated group. Based on the response of individual
      warts to the 2 treatment regimens, the clearance rate was 42.6% (20/47) for the
      PE treated group and 25% (15/56) for the PB treated group after 1 week treatment
      (ns). At 6 weeks follow-up, the clearance rate for the PE treated group and the
      PB treated group were 85.1% (40/47) and 73.2% (41/56) respectively (ns). Skin
      irritation including superficial erosions, pain and itch were observed in 47%
      (8/17) in patients treated with PE compared to 38.9% (7/18) in patients treated
      with PB (ns) during the 6 weeks follow-up period. The clearance rate of patients
      treated with PE (0.25%) was compared to those treated with PE (0.5%). Four out of
      six of PE (0.25%) treated patients had clearance of warts after 1 week and 100%
      clearance at the end of 6 weeks. None experienced any skin irritation.
      CONCLUSION: This study demonstrates that 0.5% podophyllin (and possibly 0.25%
      podophyllin) in ethanol is effective in eradicating penile warts. It can be used
      by patients for self-treatment at home with greater convenience and is more cost
      effective than the conventional podophyllin 25% in tincture benzoin paint.

PMID- 9557100
TI  - Anomalous pancreatico-biliary junction--a non-dilated biliary system and
      gallbladder carcinoma.
AB  - Anomalous pancreatico-biliary junction (APBJ) is commonly associated with cystic
      dilatation of the bile ducts but recently, several cases without the cystic
      dilatation have been reported. We treated a young female patient with intractable
      back and epigastric pain of three months duration. The spine was normal on
      magnetic resonance imaging (MRI), but several lymph nodes were seen around the
      coeliac axis. An APBJ, a non-cystic biliary system, non-filling of the
      gallbladder and an irregular right margin of the bile duct were evident on
      endoscopic retrograde pancreatography (ERCP), which was highly suggestive of
      gallbladder (GB) malignancy. At surgery, the GB was hard with local infiltration
      of the bile duct. Numerous large para-aortic and supraduodenal lymph nodes were
      present and only a biopsy was possible. Details of the case are presented and the
      growing etiological importance of an APBJ, especially without cystic biliary
      dilatation in gallbladder carcinogenesis is discussed.

PMID- 9557099
TI  - Audit of changes in serum urea and electrolytes following peri-operative
      intravenous fluid therapy.
AB  - One thousand and eleven patients discharged from the postoperative recovery ward
      with intravenous infusions were reviewed in order to audit the extent of
      assessment of serum urea and electrolytes (U&Es) and the change in serum U&Es
      over the perioperative period. 69.7% had preoperative U&Es estimation, 42.5% had
      both a pre- and postoperative estimation and in 5%, only a postoperative estimate
      was undertaken. 12.2% of patients whose U&Es were measured had an abnormal
      preoperative serum potassium compared to 17.2% postoperatively (NS). Compared to
      a preoperative incidence of 13%, more patients (27.3%) had an abnormal
      postoperative serum sodium (p < 0.0001). There was a tendency towards
      postoperative hyponatraemia: 10.0% in the preoperative period compared to a
      postoperative 25.3% (p < 0.0001). More tests were performed in the elderly (83.9%
      in age > 65 years versus 69% in age 17-64-p < 0.0001) who were more likely to
      have electrolyte disturbances preoperative hypokalaemia (p < 0.05), postoperative
      hyperkalaemia (p < 0.05), postoperative hyponatraemia (p < 0.03) and raised serum
      urea, both pre- and postoperatively (p < 0.0001 and p < 0.0005 respectively).
      Patients undergoing intraabdominal procedures did not have significantly
      different peri-operative electrolyte abnormalities. Fewer tests were performed in
      emergency patients, who were hypokalaemic in the postoperative period compared to
      elective patients (p < 0.01). There was a higher incidence of preoperative
      hyponatraemia and raised serum urea in the emergency group (p < 0.001 and p <
      0.0002 respectively). Neurosurgical emergencies often had a degree of
      preoperative hypokalaemia which persisted after surgery (p < 0.0001). Results
      indicate an increased risk of serum electrolyte abnormalities following peri
      operative intravenous fluid therapy. However in the majority of patients, the
      magnitude of the change is not significant clinically.

PMID- 9557101
TI  - Case report of Usher's syndrome in two sisters--first reported case in Singapore.
AB  - A 28-year-old Chinese woman presented with poor night vision since childhood.
      Ocular examination showed pigmentary retinopathy and systemic examination
      revealed sensorineural hearing loss. Family history showed a similar condition in
      her youngest sister. Ocular and systemic examination of her sister showed similar
      findings. This is presented as the first case report of Usher's syndrome in
      Singapore. A general discussion of Usher's syndrome is also presented.

PMID- 9557102
TI  - Left mesocolic hernia or peritoneal encapsulation?--a case report.
AB  - This is a case report of an 11-year-old boy with left mesocolic hernia. This
      condition is very similar to peritoneal encapsulation and a literature review of
      both conditions is done. Confusion among authors in naming them accordingly is
      addressed.

PMID- 9557103
TI  - Spiral computed tomography demonstration of active haemorrhage in blunt abdominal
      trauma.
AB  - In blunt abdominal trauma, patients may still be actively bleeding despite being
      physiologically stable. Fast computed tomography scanning permits the detection
      of active haemorrhage by localising the site of extravasation of contrast
      enhanced blood. Though a specific sign of active bleeding, particularly arterial
      haemorrhage, it is insensitive to the slow, continuous venous oozing associated
      with retroperitoneal and pelvic skeletal injuries. However, its presence will
      have a critical influence on further surgical intervention. The imaging features
      of this uncommon entity are demonstrated in our case report.

PMID- 9557104
TI  - What you need to know: acute primary angle closure glaucoma.

PMID- 9557105
TI  - What you need to know: detecting alcohol problems in general medical practice.
AB  - In the US, about 11% to 20% of patients presenting to general medical clinics are
      diagnosed as suffering from alcohol abuse or dependence. Alcohol screening in
      primary care settings, whether in the US or Singapore, can utilise various
      strategies for the early detection of alcohol problems. This paper briefly
      reviews several self-reports and screening procedures to assist general
      practitioners in identifying problem drinkers. The use of CAGE questionnaire,
      MAST, and its variation, SAAST and the AUDIT, are discussed and evaluated.
      Likewise, useful biochemical markers of excessive alcohol consumption like the
      liver enzymes (AST, ALT, GGT), MCV, CDT are described. They can be combined with
      each other to improve validity or used in conjunction with self-report screening
      tests for more accurate detection of problem drinkers. In particular, use of the
      AUDIT for routine screening of alcohol problems in primary care settings is
      recommended. Selective administration to those with at least two drinks per
      setting can overcome time constraints. Alternatively, sequential screening
      utilising the TRAUMA questionnaire with frequency and quantity questions
      administered to higher frequency drinkers can circumvent concerns about direct
      questioning. Use of self-reports and when possible, biochemical screening for
      alcohol problems should be a standard part of primary care practice.

PMID- 9557106
TI  - The Malai Ika Daigaku (Syonan Medical College) in Malacca (1944 to 1945) during
      the Japanese occupation of Singapore and Malaya.
AB  - During the Japanese Occupation of Singapore and Malaya (1941-1945), Singapore was
      renamed Syonan (or Syonanto) and Malaya was called Malai (or Marai; Marei). On 27
      April 2603 (1943) the Japanese Military Administration established. The Marai Ika
      Daigaku (Syonan Medical College) at the Tan Tock Seng Hospital (Hakuai Byoin),
      Syonan. The Medical College shifted to the General Hospital, Malacca in February
      2604 (1944) where it functioned till the end of the Japanese Occupation in
      September 2605 (1945).

PMID- 9557107
TI  - Geriatric medicine perspectives from the United States.

PMID- 9557108
TI  - Nonspecific inhalative challenge tests--methods and importance.
AB  - Nonspecific bronchial hyperresponsiveness is a common symptom, the prevalence
      depends especially on the inhalative exposure and on the status of atopy. Testing
      of nonspecific bronchial hyperresponsiveness is easy to perform and can be done
      with different methods. They all are reliable and safe for the patient. To assess
      the result of provocation challenge, it is necessary to look at all lung function
      parameters as well as on the clinical signs. A lot of persons with nonspecific
      bronchial hyperresponsiveness develop a constant airway disease within the next
      years. So, early detection of nonspecific bronchial hyperresponsiveness is very
      important to control these patients or for starting therapy.

PMID- 9557109
TI  - Chronic bronchitis--alterations of the bronchial mucosa.
AB  - The mucociliary transport system is usually an important defense system which
      protects the body against a variety of noxious agents. Reactions of the bronchial
      mucosa to chronic infections are seen in the ciliated cells, the amount of
      globlet cells, in modifications of the basement membrane underlying the bronchial
      epithelium and an altered percentage of inflammatory cells. In ciliated cells the
      following atypia can be seen: thickening of the ciliar membrane, swollen cilia,
      formation of compound cilia, disarrangement of microtubules. Common alterations
      of the basement membrane are: increased diameter of the basement membrane zone,
      inhomogeneous staining pattern of the basement membrane zone, formation of
      cytoplasmatic protrusions, formation of double layers of the basement membrane
      and increased number of cytoplasmatic bound vesicles. Structural abnormalities of
      the basement membrane will lead to disturbances of the zone of transition and
      have to be interpreted as a sign of disregulation in the process of diffusion and
      resorption. The inflammatory response of the epithelium during chronic bronchitis
      and asthma shows many similarities. The bronchial epithelium has a specific
      reaction pattern which supports the response against different noxious agents. So
      all findings have to be interpreted as unspecific pathological changes. All
      alterations may show different degrees of severity and are dependent on
      individual pattern and the severity of chronic process. Electronmicroscopical
      examinations in combination with lightmicroscopical findings and immuno
      histochemistry and seen in context with clinical data help to understand the
      mechanism of the inflammatory process.

PMID- 9557110
TI  - [Apgar score and umbilical cord blood pH, Fisher's index and amniotic fluid index
      AFI].
AB  - The relation between umbilical cord blood pH intra partum cardiotocography,
      amniotic fluid index and Apgar score was studied in 32 newborns. We found that
      cord blood pH, intra partum cardiotocography, amniotic fluid index, and Apgar
      score were rather poorly related.

PMID- 9557111
TI  - [Esophagogastric bypass anastomosis for benign stricture of cardia].
AB  - The aim of the study is to discuss our observations concerning oesophagogastric
      bypass anastomosis in cases with scar stricture of cardia in long-term achalasia
      (megaoesophagus). The Heller operation is ineffective in such patients and the
      resection of cardia with oesophagogastric anastomosis is a large and
      controversial operation. 16 patients were operated (6 of them after ineffective
      cardiomyotomy). In all cases long-term dysphagia, big loss of weight and large, S
      shaped oesophagus lying on the diaphragm were found. The left side thoracotomy
      was performed and fundus of the stomach was dislocated to the chest through
      dilatatored oesophageal hiatus and with the oesophagus above the cardia. There
      were no postoperative complications. However, dysphagia regressed. The remote
      results (from 1 year to 7 years) in 11 patients were analysed. The general
      condition was satisfactory. No dysphagia and gastrooesophageal reflux was
      revealed. Anastomosis was efficient in X-ray examination. Our observations
      indicate that oesophagogastric anastomosis is a procedure of choice in the
      treatment of long-term achalasia with stricture of cardia and megaoesophagus.

PMID- 9557112
TI  - [Investigations on the pathogenesis of primary varicose veins].
AB  - The data from the clinical course and epidemiology of primary varicose veins of
      lower limb suggest that sex hormones can directly influence the development of
      the disease through their intracellular receptor localised in cells of venous
      wall. The purpose of this study was to determine the stereometric differences in
      the structure of healthy and varicose veins of lower limb and to determine the
      presence and localisation of oestrogen and progesterone receptors in the cells of
      vein. The segments of greater saphenous vein obtained from the 8 women operated
      for varicose vein were used for the study. The segments of the greater saphenous
      vein obtained from 8 women that underwent femoro-popliteal venous bypass
      procedure were used as control group. The vein samples for stereometric analysis
      were preserved in Buin's solution, embedded in paraffin and then evaluated with
      automatic analyser MagiCal. To determine the presence of oestrogen and
      progesterone receptors the immunohistochemic analysis LAB with monoclonal
      antibodies produced by DAKO was used. The decreased smooth muscle fraction in
      venous wall, thickening of adventitia, the change of the smooth muscle cells to
      stroma cells ratio in the muscular layer of venous wall and change of muscular
      layer to adventitia ratio were observed in varicose veins in comparison with
      control group. The oestrogen receptors were found in the nuclei of the smooth
      muscle cells and endothelium. The progesterone receptors were localised in nuclei
      of smooth muscle cells and cells of subendothelial layer. It seems that
      quantitative analysis of sex hormones receptor in the venous wall could be useful
      in the determination of patients with increased risk of the development of
      primary varicose veins.

PMID- 9557113
TI  - [Evaluation of bone mass density after extensive resections within the alimentary
      tract].
AB  - The authors have examined a group of 30 patients at 24-36 months after extensive
      resections within the alimentary tract. The bone density assessment has been
      done. The results were compared to those obtained from another group of 30
      patients awaiting sinister operations. Bone loss was found in all postoperative
      patients. However, it was statistically significant only in patients after
      pancreatoduodenectomy.

PMID- 9557114
TI  - Pregnancy and delivery prognostic risk score for women with congenital heart
      disease and acquired valvular heart disease.
AB  - Hemodynamic changes related to pregnancy in women with Congenital Heart Disease
      (ConHD) or Acquired Valvular Heart Disease (AVHD) require special medical care
      during pregnancy and especially immediately prior to, and after delivery.
      Following a five year retrospective study (1978-1982), the authors monitored
      prospectively over a period of 12 years (1983-1994), 378 pregnancies in 252 women
      with ConHD and AVHD. Based on the results of the initial clinical examination and
      monthly follow-up visits, a numerical risk score was assigned for each patient.
      The study showed good conformity between the predictive risk score values and the
      patient's condition in the course of pregnancy and delivery. Thus, this method
      represents a novel and potentially very useful clinical tool for management of
      pregnancy in patients with ConHD and AVHD.

PMID- 9557115
TI  - [The effect of long-term therapy of obstructive sleep apnea syndrome with CPAP
      for symptoms of daytime sleepiness].
AB  - The study was undertaken to investigate whether a long-term CPAP therapy improves
      the symptoms of daytime sleepiness in patients with the obstructive sleep apnoea
      syndrome. Seventy six patients (72 men and 4 women) with AHI = 53(+/- SE = 3),
      BMI 35 (+/- SE = 0.8), mean age 46.3 (+/- SE = 11.4) have undergone CPAP therapy
      for at least one year (mean: 2.48 +/- SE = 0.33). The aggravation of alterations
      of the daytime sleepiness was estimated using the questionnaire from Sleep
      Laboratory at the Marburg University and the Epworth Sleepiness Scale (ESS).
      After the CPAP therapy, we have observed the decrease of the symptoms of the
      excessive daytime sleepiness (p < 0.001). Negative correlation between CPAP
      compliance and ESS outcome was observed (r = 0.4; p < 0.001). There was not
      correlation between the term of using CPAP and the degree of the complaints
      decrease.

PMID- 9557116
TI  - [The effect of ischemic preconditioning on early death in acute Q-wave myocardial
      infarction].
AB  - Ischaemic preconditioning is still a laboratory-based phenomenon, not
      conclusively documented in patients. In this study it was of interest whether
      there is any beneficial influence of ischemic preconditioning on 30-day in
      hospital mortality in patients undergoing acute Q-wave myocardial infarction. All
      men and women admitted to our ward between December 1994 and July 1996 with their
      first acute Q-wave myocardial infarction were divided into two groups. I group-
      29 patients with prodromal angina, defined as chest pain episodes in the 24-hour
      period before myocardial infarction. II group--25 patients who showed no chest
      pain before infarction onset. Both groups did not differ statistically in view of
      age, sex, smoking habits and adjunctive therapy. The use of streptokinase in the
      I and II group was also similar--in 58.6% and 56% of patients respectively in the
      first and second group. In the I group there was no fatal outcome, all 5 death
      cases occurred in the II group. The results are statistically significant and
      suggest lower in-hospital mortality in Q-wave myocardial infarction patients with
      previous ischaemic preconditioning.

PMID- 9557117
TI  - [Neurologic manifestations of HIV infections and AIDS].
AB  - The paper presents the review of neurological manifestations of HIV infection.
      The pathogenesis of changes caused by HIV within central nervous system is
      discussed. The most common neurological syndromes occurring in AIDS patients as
      well as the division of these changes concerning peripheral and central nervous
      system are described.

PMID- 9557118
TI  - [Sepsis in surgery: pathogenesis, new therapeutic approaches].
AB  - Sepsis and septic shock are phenomena with a characteristic clinical picture and
      etiologically related to injury. Chains of events from injury (e.g., infection)
      through activation of immunological system to multiple organ failure are
      responsible for sepsis. Neutralization of endotoxins, TNF, interleukins and so
      on, can improve the treatment of sepsis in the future.

PMID- 9557119
TI  - [Glucocorticosteroids in bronchial asthma. II. Use of cortisol markers in various
      biological materials for evaluation of adrenocortical function].
AB  - Glucocorticosteroids (GS) being widely used in asthma treatment are sometimes
      applied in high doses and for long period. This treatment is often connected with
      adrenocortical suppression. Adrenocortical function assessment in GS treated
      patients with different doses and forms of drug is of great diagnostic and
      prognostic importance. In the presented work the methods of adrenocortical
      function assessment are discussed, especially serum cortisol level and non
      invasive: saliva and urine cortisol assays.

PMID- 9557120
TI  - [Headaches as the main symptom of advanced craniopharyngioma in a 14-year old
      girl].
AB  - Craniopharyngioma of advanced stage in a 14-year old girl is described. The only
      symptom of the disease through the one year before recognition was cephalea. The
      disclosure of calcifications in the x-ray image of sella turcica region helped to
      establish diagnosis.

PMID- 9557121
TI  - [Urinary diversion to the large intestine in adults].
AB  - The paper presents the history of technique and concepts of urinary diversion to
      colon and rectum from the mid-XIXth century until today, including the
      contribution of Polish surgeons--Krynski, Laskownicki and Kielkiewicz.
      Contraindications and complications of this type of definitive urinary diversion
      is briefly discussed. Authors also present the outcome of ureterosigmoidostomy
      performed according to method proposed by Goodwin in 25 patients cystectomized
      for infiltrating transitional cell carcinoma of the bladder, who were operated on
      at the Department of Urology, Medical School in Warsaw. These patients were in
      poor general condition and short life expectancy, which depended upon tumour
      stage and grade as well as preoperative urographic evaluation of urinary tract.

PMID- 9557123
TI  - Cutaneous, multilocular T-cell lymphosarcoma in a horse--clinical,
      ultrasonographic and pathological findings.
AB  - Clinical, ultrasonographic and pathological findings of a cutaneous, multilocular
      T-cell lymphosarcoma (malignant lymphoma) in a 13-year-old, brown Austrian
      warmblood mare are reported. The horse was under clinical observation, and the
      tumours were sonographically monitored over an 8 month period, revealing
      worsening of body condition, weight loss, lameness of the left hindlimb and a
      slight increase in the tumours size. Most of the tumours were covered by normal
      skin, one showed ulceration. Ultrasonography of the tumours allowed accurate
      anatomical localization in relation to the adjoining tissue, assessment of their
      internal structure, of involvement of adjacent muscles and of a regional lymph
      node, and it facilitated the percutaneous fine-needle aspiration. Necropsy
      confirmed muscular infiltration in three locations. Light microscopy and
      immunohistology led to the diagnosis of a T-cell lymphosarcoma.

PMID- 9557122
TI  - Immunohistological examination on the distribution of collagen types I, III, IV
      and V in bovine post partum placentomes.
AB  - This paper describes the in situ presence and distribution of collagen types I,
      III, IV and V in the bovine placenta. The objective was to determine whether
      there are qualitative and/or quantitative differences in the collagen content of
      placentomes originating from cows with retained placenta and cows with normal
      discharge of placenta. Twelve h post partum discharge of the placenta or the
      incidence of retained placenta was monitored. From 57 cows one placentome per cow
      was collected within 1 h post partum. The cows were divided into three groups:
      retained placenta after caesarean section (Group 1), retained placenta after
      spontaneous calving (Group 2) and normal discharge of placenta within 12 h post
      partum after spontaneous calving (Group 3). A pilot study was conducted to
      establish the technique of collecting the placentomes and to verify the applied
      immunohistological methods used in this work. In the following study, 32
      placentomes were used to determine the amount of collagen (types I, III, IV and
      V) with qualitative and semi-quantitative methods using immunohistochemical
      techniques. Collagen types I, III, IV and V were found in large quantities in the
      maternal tissue. In the fetal connective tissue the amount of these collagen
      types was smaller. In the placentomes of the three groups, no qualitative or
      quantitative differences could be detected.

PMID- 9557124
TI  - Evidence of the existence of alpha 1B-adrenoceptors on hepatocytes of domestic
      fowl (Gallus domesticus).
AB  - In liver cell membranes of laying hens alpha 1-adrenergic receptors were
      characterized using 3H-prazosin. Specific binding was saturable and indicative of
      a single class of high-affinity binding sites with a KD of 0.40 +/- 16 nM and a
      Bmax of 390 +/- 38 fmol/mg membrane protein. Preincubation of membranes with
      chlorethylclonidine significantly diminished the binding of 3H-prazosin (Bmax =
      99 +/- 14 fmol/mg membrane protein). Furthermore, competition experiments
      revealed a rank order of prazosin >> phentolamine = oxymetazoline >> WB 4101,
      with Ki values of 0.71 +/- 0.62, 20 +/- 6, 32 +/- 13, and 119 +/- 48 nM,
      respectively. These results suggest the existence of alpha 1B-adrenergic
      receptors in hen liver cell membranes.

PMID- 9557126
TI  - Assessment of subacute mammary inflammation by soluble biomarkers in comparison
      to somatic cell counts in quarter milk samples from dairy cows.
AB  - The usefulness of soluble markers in indirectly differentiating inflamed quarters
      from healthy quarters of 30 Holstein Friesian cows was tested over a follow-up
      period of 20 weeks. In comparison to N-acetyl-beta-D-glucosaminidase (NAGase),
      lactate dehydrogenase (LDH), Na+, K+ and Cl- the somatic cell counts (SCC) were
      determined in foremilk samples. The soluble parameters were measured by means of
      an autoanalyzer system (Beckman CX5CE) equipped with solid state ion electrodes.
      Due to different types of inflammatory reactions it is considered to be
      advantageous to perform two tests in parallel for assessing the mammary gland
      status. Cell-damaging processes should best be detected by measuring elevated LDH
      activity, whereas the impairment of the blood-udder barrier is recorded by the
      respective elevation of the indicators Na+ and Cl-. Among all variables, SCC
      included, the soluble parameters showed the least dispersions, whereas those of
      SCC were the most unfavourable in this respect. Moreover, NAGase/LDH and Na+/Cl-
      among all variables had the highest correlation coefficients of 0.85 and 0.86,
      respectively. Threshold values as decision limits are proposed. Additionally, an
      inter-quarter comparison and evaluation improved the diagnostic value of each
      indirect mastitis parameter analyzed. By means of discriminant analysis, it is
      shown that the distribution of inflammation within the udders of this herd was
      unequal.

PMID- 9557125
TI  - Field isolates of Mycoplasma ovipneumoniae exhibit distinct cytopathic effects in
      ovine tracheal organ cultures.
AB  - Ovine tracheal ring explants were infected with four different Mycoplasma
      ovipneumoniae and one M. arginini field isolate and their ability to induce
      cytopathic effects was tested by measuring ciliary activity and intracellular
      calmodulin release. Infected tracheal rings showed significantly decreased
      ciliary activity as compared to the non-infected control rings. There were,
      however, marked differences between isolates in the onset and severity of the
      effects which correlated with their ability to produce hydrogen peroxide.
      Infected tracheal rings released more calmodulin than the non-infected controls.
      The amount of calmodulin released also varied between isolates, and somewhat
      reflected the degree of loss of ciliary activity in the corresponding rings
      induced by the different isolates. Light and electron microscopic examinations of
      infected tracheal rings revealed disorganisation and sloughing of the epithelium,
      and association of mycoplasmas only with the cilia. Following repeated in vitro
      passages, the organisms had reduced ability to inhibit ciliary activity which
      correlated with decreased hydrogen peroxide production. Addition of catalase to
      the organ cultures delayed loss of ciliary activity. These results suggest that
      M. ovipneumoniae induced ciliostasis in ovine tracheal ring explants which
      correlated with hydrogen peroxide production. Furthermore, these M. ovipneumoniae
      induced injuries to respiratory epithelial cells could contribute to the role
      that this organism may play in sheep respiratory disease.

PMID- 9557127
TI  - Evaluation of the efficacy of perorally administered glutamic acid-chelated iron
      and iron-dextran injected subcutaneously in Duroc and Norwegian Landrace piglets.
AB  - The goals of this study were to evaluate the effect of orally administered amino
      acid-chelated iron (Fe) compared to injected Fe-dextran on haematology and weight
      gain in two different breeds raised under commercial conditions. Altogether 92
      Duroc (D) pigs and 84 Norwegian Landrace (L) pigs from two different herds were
      included in the study. The day after birth the litters were divided in two groups
      (split litters). Group (Gr.) 1 was given 4 ml of a 50% solution of Super Fe-MAX
      (52 mg glutamic acid-chelated Fe in a water solution) orally, while Gr. 2 was
      subcutaneously (s.c.) injected with Idofer (180 mg Fe as ferridextran). Until
      weaning at 5 weeks, all the piglets had free access to a 3% solution of Super Fe
      MAX (0.78 mg Fe/ml), access to pelleted food being given from 1 week of age. The
      piglets were weighed and bled before treatment the day after birth (day 1) and on
      days 4, 7, 14, 21 and 35. All piglets were weighed on days 28 and 49, while 72 of
      the L pigs were also weighed on days 77, 98 and 119. At weaning D pigs in Gr. 1
      and Gr. 2 had a mean body weight of 8.64 kg and 8.30 kg, respectively, the
      corresponding figures for the L pigs being 10.82 kg and 10.34 kg. As regards the
      72 L pigs followed to day 119, the mean weight in Gr. 1 and Gr. 2 was 80.6 kg and
      80.2 kg, respectively. A significantly lower weight gain in the piglets with a
      birth weight below 1.2 kg in Gr. 2 compared with Gr. 1 indicated that excess
      administration of Fe to small piglets may have a detrimental effect on weight
      gain. From day 7 (D pigs) and on days 14 and 21 (L pigs), Gr. 2 had a
      significantly higher haemoglobin concentration (Hb) than Gr. 1. Nevertheless, Hb
      levels were also adequate in Gr. 1 in both breeds. There was a negative
      correlation between changes in Hb during the first weeks and the initial value.
      Though haematological values seemed to show inter-breed differences, with higher
      average erythrocyte counts (RBC) and Hb and lower mean cell volume (MCV) in the D
      pigs, the ability to avoid Fe deficiency nevertheless appeared to be the same in
      both breeds.

PMID- 9557128
TI  - Infectious bovine mastitis caused by environmental organisms.
AB  - The purpose of this study was to determine the prevalence of environmental
      mastitis in dairy herds and identify the main environmental pathogens, and to
      evaluate the influence of season, housing and management. A total of 20,310
      quarters of 5216 animals from 52 dairy herds in 32 counties was examined. Milk
      samples were aseptically collected for laboratory examination from mammary glands
      testing positive to any of the field tests. From these, 736 environmental
      infections were identified. The most frequently isolated environmental pathogens
      were algae of the genus Prototheca sp. (41.2%), Streptococcus uberis (21.1%),
      fungi (19.5%), enterobacteriacea (8.3%) and Nocardia sp. (6.6%). The occurrence
      of mastitis was not influenced by the herd size, use of dry cow therapy, or post
      milking teat dipping. A tendency for increased occurrence of environmental
      mastitis during the months of September to February (hot and wet weather) was
      observed, suggesting a seasonal influence.

PMID- 9557129
TI  - Cytological, immunocytochemical and biochemical cerebrospinal fluid
      investigations in selected central nervous system disorders of dogs.
AB  - Cerebrospinal fluid (CSF) obtained from 20 clinically healthy dogs and from 15
      dogs affected by neurological disorders were examined for total and differential
      cell counts, immunocytochemistry for canine distemper virus antigen, total
      protein concentration and electrophoretic separation, and glucose and enzyme
      determination. Dogs affected by canine distemper showed an increase in
      macrophages, presence of specific inclusion bodies, and an increase in total
      protein concentration and gamma-globulin fraction. In bacterial
      meningoencephalomyelitis pleocytosis, increase of total proteins with special
      regard to high molecular weight proteins, elevated levels of lactate
      dehydrogenase (LDH), alterations of LDH isoenzyme profile, and decrease in
      glucose levels were detected; inflammatory disorders were more often
      characterized by an increase in LDH level, while in non-inflammatory disorders
      (hydrocephalus and spinal cord neoplasia) no variation in LDH levels was
      detected. Analysis of CSF in dogs appears relatively easy to perform and may help
      in establishing the condition of the blood-brain barrier as well as in the
      diagnosis of neurological disorders.

PMID- 9557130
TI  - Identification and characterization of Arcobacter isolates from broilers by
      biochemical tests, antimicrobial resistance patterns and plasmid analysis.
AB  - A total of 89 Arcobacter butzleri isolates obtained from freshly slaughtered
      broilers was investigated for their biochemical capacities by using the API CAMPY
      system as well as additional growth and tolerance tests, for their antimicrobial
      resistance patterns and their plasmid content. Among these techniques,
      biochemical profiling and antimicrobial resistance testing proved to be the most
      discriminatory methods as confirmed by the calculation of discriminatory indices.
      These two methods might represent valuable tools for epidemiological analysis of
      A. butzleri isolates. Small plasmids of up to 5 kbp were detectable in only 21 of
      the 89 isolates while the remaining 68 A. butzleri isolates were plasmid-free.

PMID- 9557132
TI  - Late lesions of experimental contagious caprine pleuropneumonia caused by
      Mycoplasma capricolum ssp. capripneumoniae.
AB  - A clinical, bacteriological, serological and patho-anatomical study was carried
      out on 12 goats surviving the acute stage of contagious caprine pleuropneumonia
      (CCPP), experimentally produced with Mycoplasma capricolum ssp. capripneumoniae
      (M. capripneumoniae), with the major aims of investigating the chronic stage of
      the disease and elucidating the possibility of a carrier state beyond the acute
      fulminant phase. The goats were killed 9, 16, 82 or 126 days after the onset of
      acute clinical signs. On day 9, clinical signs included low grade fever and
      persistent coughing. Thereafter, only intermittent coughing was recorded. Serum
      titres of complement-fixing antibodies to M. capripneumoniae were high at the
      period of fever but dropped thereafter. Post-mortem examination showed acute
      fibrinous pleuropneumonia on days 9 and 16, and chronic pleuropneumonia on days
      82 and 126, including sequester formations in goats killed on day 126. Mycoplasma
      capripneumoniae was isolated on days 9 and 16 but not on later occasions. The
      study showed that goats recovered from acute CCPP may have lesions for a long
      time thereafter but provide no evidence of a carrier state among long-term
      survivors.

PMID- 9557131
TI  - A Salmonella monitoring programme in egg production farms in Germany.
AB  - A programme monitoring the prevalence of Salmonella infections in egg production
      farms with different types of flock management was conducted over a period of 18
      months. Three laying hen farms with floor pens and five farms with batteries were
      examined from September 1992 to March 1994. A total of 569 samples (293 feed and
      276 faeces) were processed in parallel by fivefold fractional enrichment in
      Rappaport/Vasiliadis medium and in potassium tetrathionate crystal violet broth.
      By using such elaborate methods, high detection rates of Salmonella were
      obtained. Two thirds of all isolates were found in the third to fifth selective
      enrichment procedure. Salmonella (S.) Tennessee was the most common serovar
      isolated (from 24.5% of the samples) whereas S. Enteritidis was the second most
      common isolate (23.7%). Salmonella were isolated from 33.1% of the feed samples
      (97/293), a result which may stimulate further discussion on the prevention of
      potential contamination of feed stuff with Salmonella and other pathogens. The
      number of Salmonella isolations from floor pens was significantly higher than
      from batteries. As time progressed an increase in the number of Salmonella
      isolations occurred in samples taken from the floor pens. The development of a
      less costly routine monitoring programme to detect Salmonella in samples taken
      from barns with layer flocks is recommended.

PMID- 9557134
TI  - KNI-577, a potent small-sized HIV protease inhibitor based on the dipeptide
      containing the hydroxymethylcarbonyl isostere as an ideal transition-state mimic.

PMID- 9557133
TI  - Control of proliferative enteropathy in growing/fattening pigs using growth
      promoters.
AB  - The aim of this study was to evaluate the effect of different antibiotics used as
      growth promoters on the control of porcine intestinal adenomatosis when
      administered in weaning, growing and fattening pig diets, according to Annex I of
      the European Union directive (70/524/EEC and its subsequent amendments to date)
      for the use of feed additives. On a farm with a previous history of proliferative
      enteropathy outbreaks, 648 weaned piglets (23 days old) were divided into nine
      experimental groups according to bodyweight and sex ratio, each group comprising
      four pens with 18 pigs in each pen. One group served the trial as a negative
      (unmedicated) control: another (the positive control) received monensin via feed
      at 100 p.p.m. up to the end of the growing phase (107 days old) and 50 p.p.m. up
      to slaughter age (156 days old). The remaining seven groups were offered feed
      with the addition of the following antibiotics: virginia-mycin (50-20 p.p.m.),
      avilamycin (40-20 p.p.m.), spiramycin (50-20 p.p.m.), zinc bacitracin (50-10
      p.p.m.), avoparcin (40-20 p.p.m.), tylosin (40-20 p.p.m.) and salinomycin (60-30
      p.p.m.), respectively. The performance of the pigs in the positive control group
      was very satisfying and among the highest in the trial, verifying earlier field
      studies. As a general conclusion it seems that all tested growth promoters had a
      beneficial effect compared with the untreated control, indicated by the decrease
      of mortality rate, the elimination of diarrhoeal incidence and the enhancement of
      growth performance, although the proliferative enteropathy control achieved by
      each substance was not always satisfactory. More specifically, the antibiotic
      growth promoters tested can be scaled according to their total efficacy as
      follows: 1. Salinomycin, tylosin, spiramycin; 2. Virginiamycin, zinc bacitracin,
      avilamycin; and 3. Avoparcin. Finally, it is considered that part of the growth
      promotion efficacy of the tested substances is due to their potential capacity to
      control porcine intestinal adenomatosis; thus, in future growth performance
      trials, the disease background of the trial farms must be examined, especially
      for porcine enteropathy challenges.

PMID- 9557135
TI  - Suramin analogues with a 2-phenylbenzimidazole moiety as partial structure;
      potential anti HIV- and angiostatic drugs, 2: Sulfanilic acid-, benzenedisulfonic
      acid-, and naphthalenetrisulfonic acid analogues.
AB  - The synthesis of suramin analogues bearing a 2-phenyl-benzimidazole moiety is
      described. Aminoarene sulfonic acids 2a-e are acylated with 3,4-dinitrobenzoyl
      chloride 3 yielding the amides 4a-e which are hydrogenated to the corresponding
      diamines 5a-e. These are treated with 3-nitrobenzaldehyde, yielding the
      azomethines 7a-e and their isomers 8a-e and 9a-e. Key step in the synthesis of
      the target compounds 12a-e is the oxidation of the azomethines with oxygen to the
      benzimidazoles 10a-e. These are hydrogenated to the amines 11a-e reacting with
      phosgene to yield the symmetric ureas 12a-e. Results of the anti-HIV, cytostatic,
      and antiangiogenic screening are presented.

PMID- 9557136
TI  - New NO-donors with antithrombotic and vasodilating activities, Part 20.
      Azodioxides activated by electron acceptors in geminal or vicinal position.
AB  - Twenty-two nitroso compounds with cyano, acyloxy, or carbonyl groups in geminal
      position were prepared, eight of them for the first time. In the solid state
      these compounds dimerize to colorless azodioxides. Exceptions are the 4
      nitrobenzoyloxynitroso compounds 7b, f, and g which form bright blue crystals. In
      vitro (Born test, collagen) considerable antiplatelet activity was observed in
      each class of compounds. Azodioxides with cyano groups in geminal position (3a,
      b) were most active (IC50 approximately 10 microM) suggesting the importance of
      strong electron withdrawing groups in geminal position to the azodioxide partial
      structure. When administered orally to rats (60 mg/kg) all compounds inhibited
      the thrombus formation in mesenteric arterioles and venules. The acetyloxy
      derivatives 5d and 5e were most active (18-21% inhibition in arterioles and 11
      15% inhibition in venules). In aqueous media at 37 degrees C the cyanonitroso
      compound 3b and the benzoyloxynitroso compound 7a decomposed to nitric oxide and
      its reduced form nitrosohydrogen. This suggests that the above pharmacological
      effects are mediated by a NO dependent mechanism.

PMID- 9557137
TI  - New NO-donors with antithrombotic and vasodilating activities, Part 21.
      Pseudonitrosites and other azodioxides with vicinal electron acceptors.
AB  - Twelve vicinally substituted nitro-nitroso compounds (pseudonitrosites) were
      synthesized, nine of them for the first time. In the solid state the dimeric
      azodioxides are present. In the class of the pseudonitrosites 2a-h, all compounds
      exhibited comparatively strong antiplatelet activity in vitro (Born test,
      collagen). Four of them showed an IC50 below 10 microM, 2a being the most active
      substance with an IC50 = 2.1 microM. When administered orally to rats (60 mg/kg)
      small antithrombotic effects were observed. The pseudonitrosite 6d was the most
      active compound (18% inhibition in arterioles). The in vitro decomposition of 2a
      at 37 degrees C gave NO and N2O, indicating that the above pharmacological
      effects were mediated by an NO-dependent mechanism. The replacement of the nitro
      group in the pseudonitrosite partial structure by other electron acceptors i.e.
      acetyl, carboxyl, or acetyloxy groups leads to inactive (10a) or less active
      compounds (10b, e).

PMID- 9557139
TI  - Nitric oxide production by cells infiltrating amphibian skin grafts.
AB  - In vivo injection of the edible frog Rana esculenta with NOS inhibitor, L-NMMA
      caused prolongation of skin allograft and xenograft viability, statistically
      significant only in the latter case. In the present studies skin allo- and
      xenografts at the latent or rejection phase were excised from the hosts (Bufo
      bufo, R. temporaria, and R. esculenta) and incubated in vitro for 24 hrs in a
      medium only or in the presence of competitive (L-NMMA, L-NAME, L-aminoguanidyne)
      and noncompetitive (dexamethasone and cycloheximide) inhibitors of NO synthesis.
      In some experiments graft infiltrating cells were washed out and cultured
      separately from the respective skin fragments. The nitrite level was measured in
      the culture supernatant using Griess reagent. The nitrite level was negligible in
      the control skins, autografts, and xenografts depleted of graft infiltrating
      cells, as well as in allo- and xenografts excised at the rejection phase. In the
      case of grafts excised at the latent phase, the nitrite amount was substantial in
      supernatant from allografts and significantly higher in xenografts. A high level
      of nitrite was also present in supernatants from graft infiltrating cells. It is
      concluded that the NO contributes to some stages of the rejection process of the
      anuran skin grafts, this contribution being especially significant in the case of
      xenografts. The main source of this agent are graft infiltrating phagocytic
      cells.

PMID- 9557140
TI  - An attempt at comparing external changes taking place during maturation of male
      mice with the development of the process of spermatogenesis.
AB  - Evaluation of the degree of sexual maturation was performed in male mice of two
      selected lines differing in respect of body weight. Four developmental stages
      were distinguished: (1) loosening of the skin between the urinary papilla and the
      anus, (2) projection of the scrotum, (3) descent of the testes to the scrotum,
      (4) demonstration of sexual drive. Histological examination of the testes
      revealed that at the first developmental stage the animals had clearly immature
      gonads. In a few, not numerous, seminiferous tubules spermatogenesis had reached
      the phase of primary spermatocytes. At the second stage of development the male
      gonads reached the phase of secondary spermatocytes and sporadically of early
      spermatids. At the third stage of the animals development, the spermatogenesis
      observed in numerous cross-sections of the seminiferous tubules reached the
      spermatid phase and in males at the fourth stage some sperm cells appeared in the
      lumen of the tubules. A greater diameter of the sperminiferous tubules was
      demonstrated in the heavy line males than in the light line animals. In males of
      the heavy line the diameter of the Leydig cells increased between the third and
      fourth stage. The investigation results suggest that the accepted criteria of
      determination of sexual maturation stages correspond to various phases of changes
      taking place in the process of spermatogenesis.

PMID- 9557141
TI  - Magnetic resonance angiography in patients with brain infarction.
AB  - This study evaluated the role of magnetic resonance angiography (MRA) in
      detecting extra- or intracranial vascular disease in 118 patients with brain
      infarction and the accuracy of MRA diagnosis when compared with conventional
      angiography in patients who had both investigations. Magnetic resonance
      angiography ruled out extra- and intracranial large vessel disease in 36% of the
      patients. MRA also demonstrated extra- or intracranial disease in 56% (probably
      symptomatic in 31, possibly symptomatic in 18, and asymptomatic in 17 patients),
      and provided no information in 8% of the 118 patients. Among the 176 major
      vessels visualized by both MRA and conventional angiography, conventional
      angiography confirmed the presence of 9/10 extracranial and 32/40 intracranial
      large vessel abnormalities detected on MRA. There were two false-negative
      findings on MRA: occlusion of a distal branch of middle cerebral artery, and an
      asymptomatic posterior cerebral artery stenosis. Magnetic resonance angiography
      is a clinically useful method for screening extra- and intracranial disease in
      patients with brain infarction and selecting high-yield patients for conventional
      angiography.

PMID- 9557138
TI  - Earthworm immune responses.
AB  - The knowledge of the immunity in annelids started with the use of earthworms as
      biomarkers indicating changes caused by environmental pollution. Defence
      strategies effectively protect earthworms against bacterial infections and
      parasitic invasion. A natural immunity formed by anatomical and chemical
      protective barriers prevents damage of the underlying tissues, body fluid losses,
      and microbial infections of the body cavity. The internal defence mechanisms of
      annelids involve phagocytosis, nodule formation and encapsulation, blood
      coagulation and wound repair, and antibacterial immune proteins. The
      antibacterial activity of coelomic fluid associated with lysozyme-like substances
      and inducible humoral molecules support haemocytic reactions in the annelid
      defence system.

PMID- 9557142
TI  - Power Doppler imaging and color Doppler flow imaging for the evaluation of normal
      and pathological vertebral arteries.
AB  - Recently, an ultrasound method for vascular applications using the amplitude of
      the reflected echosignal for the generation of intravascular color signals has
      been introduced. We compared the utility of this power Doppler imaging (PDI) with
      conventional color Doppler flow imaging (CDFI) for examination of vertebral
      arteries (VA). Forty-nine patients with signs and symptoms suggesting ischemia
      within the posterior circulation were evaluated. Quality of blood flow
      visualization by PDI and CDFI at the different VA segments was classified
      according to a four point scale. Furthermore, combined sonographic findings were
      correlated with the results of digital substraction and/or magnetic resonance
      angiography (DSA, MRA). Power Doppler imaging provided a significantly superior
      visualization of the intertransversal VA, whereas display of the intracranial V4
      segment was superior significantly on CDFI. Both methods were complementary for
      the evaluation of the VA at the origin. With respect to the angiographic
      findings, combined CDFI and PDI achieved a sensitivity of 90.63% and a
      specificity of 97.22% for the differentiation of healthy and pathologic VAs.
      Power Doppler imaging is complementary to CDFI for the sonographic assessment of
      VA disease. Combined use of PDI and CDFI achieves a high sensitivity and
      specificity, thus increasing diagnostic confidence.

PMID- 9557143
TI  - Observer variability in the measurement of the size of intracranial aneurysms
      using power TCD.
AB  - This study assessed the observer variability for measurement of intracranial
      aneurysmal size visualized on color "power" Transcranial Doppler Ultrasound
      (TCD). Patients with recent subarachnoid hemorrhage underwent color "power" TCD
      blind to angiography. Identified aneurysms were measured from the frozen image
      (in real time or from video tape) using the trackball function. Two observers
      measured the maximum (systolic) and minimum (end diastolic) area of each
      aneurysm, and an adjacent reference artery. Each observer was blind to the
      other's results. Interobserver variability was assessed using the Bland and
      Altman technique. Thirty-nine aneurysms were identified in 32 patients in 10
      months. The maximum cross-sectional area of the aneurysm was 38:41 mm2 (observer
      1:observer 2), and the mean difference was -3 mm2 (95% confidence interval [CI]
      of the difference -5.4-1.46 mm2). The maximum cross-sectional area of the
      reference artery was 26:28 mm2 (observer 1:observer 2), and the mean difference
      was -2 mm2 (95% CI -5.7-1.2 mm2). Neither difference was significant.
      Intraobserver reliability also was good. The measurement of intracranial aneurysm
      and artery size with power TCD is reliable sufficiently for use in longitudinal
      studies of changes in aneurysm size.

PMID- 9557144
TI  - SPECT and lumbar MRI in back pain with emphasis on changes in end plates in
      association with disc degeneration.
AB  - Over a two-year period, 48 sequential patients were selected because they showed
      type I or II end plate changes on magnetic resonance imaging (MRI) and/or had
      positive single-photon emission computerized tomography (SPECT) scan in the area
      of disc degeneration. They were selected out of a large group of patients who
      were being evaluated by MRI and SPECT scan for low back pain. In this group of 48
      patients, 47 had positive SPECT scans at the disc space, which on MRI indicates
      degenerative disc disease. Of these, 38 had end plate changes on the MRI, but 10
      did not have end plate changes on the MRI even though their SPECT was positive.
      None of the 48 patients had evidence of other pathology such as fracture,
      metastatic disease or spondylolysis. The MRI changes were both of type I and type
      II and thought to represent increased vascularization of the fibrous tissue or
      fatty replacement of marrow in the area of the end plate. Based on this study, we
      are proposing that a positive end plate SPECT in degenerative disc disease is
      related to marrow changes in the region of the end plate of the disc. Also, we
      are proposing that SPECT may be of value in delineating early end plate changes
      prior to the MRI showing type I or type II change in the same area.

PMID- 9557145
TI  - The influence of different gases on acoustic properties of a spherosome-based
      ultrasound contrast agent (BY963). A transcranial Dopplersonography study.
AB  - Ultrasound contrast agents improve the signal-to-noise ratio of reflected
      ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog
      studies, we investigated the time course of TCD signal amplitude after
      application of a phospholipid-containing ultrasound contrast agent (BY963) filled
      with different gases. The median time of Doppler amplitude enhancement exceeding
      5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air
      , argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds
      respectively). The decrease of time-intensity curve and the duration of signal
      enhancement showed significant differences comparing the different gases (p =
      0.04 and 0.03, respectively). The time course of in vitro stability of BY963
      agitated with the different gases measured by absorbance of light (500 nm) showed
      a retarded decay for perfluoropentane, a rapid decrease for air, isopentane,
      trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane.
      The time course of the different gases depended on the physiochemical properties
      (lipophilicity and the solubility in water) of the gas encoated in the
      phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro
      stability and the longest duration of TCD enhancement compared with the other
      gases used.

PMID- 9557146
TI  - A preliminary study comparing the sensitivity of serial monthly enhanced MRI
      after standard and triple dose gadolinium-DTPA for monitoring disease activity in
      primary progressive multiple sclerosis.
AB  - We performed this study to evaluate and compare the numbers of total and new
      enhancing lesions detected on serial monthly brain magnetic resonance imaging
      (MRI) after the injection of a standard dose (SD) and a triple dose (TD) of
      gadolinium-DTPA (Gd) in patients with primary progressive multiple sclerosis
      (PPMS). Every 4 weeks for 3 months and in two separate sessions, MRI scans were
      obtained from 5 patients with PPMS, 5 (early) and 20 minutes (delayed) after SD
      (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. In 2 patients, T1-weighted scans
      with a magnetization transfer pulse (MT) after SD and TD injection were also
      obtained. There were 13 enhancing lesions (5 of which were new) on the early SD
      scans, 15 (5 new) on the delayed SD scans, 17 (6 new) on the early TD scans and
      18 (7 new) on the delayed TD scans. TD MRI scans detected more enhancing lesions
      than SD scans in 3 patients (two of them were those with the lowest disability).
      The application of the MT pulse did not change the numbers of enhancing lesions
      seen after the injection of SD and TD of Gd in the remaining two patients. No
      side effects were reported and no significant changes in blood test parameters
      were found throughout the study. Our results suggest that serial monthly TD MRI,
      delayed scanning, MT T1-weighted scans or their combination, although safe, have
      a limited role for monitoring disease evolution in patients with PPMS.

PMID- 9557148
TI  - Calcified cystic lesions in a patient with epilepsy and progressive dementia.
AB  - A 67-year-old woman had intractable epilepsy and developed a progressive dementia
      with upper motor neuron signs over the last 6 years. Magnetic resonance imaging
      (MRI) revealed multiple areas of large calcified cysts, which increased in number
      and size over the last 3 years. Discussion includes the appearance of these
      lesions radiologically and pathologically, as well as their differential
      diagnosis and clinical significance, focusing on the increasing detection of
      these lesions with current imaging techniques.

PMID- 9557147
TI  - Three-dimensional reconstruction of the power flow Doppler imaging of
      intracranial vascular structures in the neonate.
AB  - Three-dimensional (3D) ultrasonography reconstructing from power flow Doppler
      imaging (PF) is able to image the 3D structures of the vascular systems. We tried
      to display the 3D images of intracranial vascular structures in 5 neonates with a
      portable data processor. Data acquisition was performed using PF through the
      anterior fontanel. We succeeded in reconstructing vivid 3D images of the anterior
      cerebral arteries (ACA), basilar artery (BA), internal carotid arteries (ICA),
      middle cerebral arteries (MCA), lenticulostriate arteries (LSA), internal
      cerebral vein (ICV), the vein of Galen (GV) and straight sinus (SS) in all
      subjects. The MCA could be displayed in only a proximal portion. The images of
      the LSAs were fainter than the other vessels. These problems are based on the
      character of PF; the flow signal, sampling from the small sized vessels and the
      perpendicular vessels to ultrasonic beam, is weak. The images of these vessels
      are fainter than other vessels. These limitations of PF performance directly
      influence the quality of the 3D images. The benefits and limitations of 3D
      ultrasonography system are discussed.

PMID- 9557149
TI  - Extrarolandic origin of spike and myoclonus activity in epilepsia partialis
      continua: a magnetoencephalographic and positron emission tomography study.
AB  - The dipole sources of interictal spike activity were localized and the myoclonus
      activity back-averaged by combined magnetoencephalography and surface
      electromyographic measurements in a child who had epilepsia partialis continua
      without a structural brain lesion. Dipole sources were matched with metabolic
      information obtained from interictal 5-fluoro-D-glucose positron emission
      tomography (PET) and superimposed onto high-resolution magnetic resonance images.
      Dipole sources of interictal epileptic discharges clustered within the inferior
      parietal cortex, which also showed a regional hypermetabolism on PET scans. The
      dipole sources of reafferent activity following myocloni in the postcentral gyrus
      were associated with a local hypometabolism Although there was no obvious phase
      relationship between interictal spikes and myoclonic jerks, the myocloni were
      initiated from within the interictal spike area in the extrarolandic cortex. The
      data demonstrate that motor symptoms may be a remote effect of epileptic activity
      within functional brain circuits.

PMID- 9557150
TI  - Isolated straight sinus thrombosis: clinical and neuroradiologic correlates.
AB  - A rare case of straight sinus thrombosis in a 36-year-old female with sudden
      onset of status migrainosus is presented. This condition was demonstrated by a
      linear density in the midline on a noncontrast computed tomography scan, as a
      filling defect at the location of straight sinus on magnetic resonance imaging,
      and by the inability to visualize blood flow in the straight sinus on magnetic
      resonance venography, with a similar demonstration on a 4-vessel digital
      subtraction angiography.

PMID- 9557151
TI  - Intra-axial posterior fossa cryptococcosis: MRI findings.
AB  - Two case reports of intra-axial posterior fossa cryptococcosis in immunocompetent
      patients are presented. Magnetic resonance findings of solitary abscesses with
      mildly irregular peripheral enhancement within the medulla, and irregular
      peripheral enhancement with a nodular component within the right cerebellum are
      described.

PMID- 9557152
TI  - Presymptomatic brain lesions on MRI in a patient with intravascular malignant
      lymphomatosis.
AB  - A 58-year-old man with a intravascular malignant lymphomatosis initially
      developed myeloradiculopathy without cerebral symptoms. His MRI, however,
      demonstrated solid, wedge-shaped, and well-demarcated lesions in the deep white
      matter and a string-shaped lesion along with nerve fibers in the splenium of
      corpus callosum. A variety of cerebral symptoms manifested a month afterward. The
      possibility of this disease should be considered in cases of undiagnosed
      myeloradiculopathy with such silent brain lesions.

PMID- 9557153
TI  - Spontaneous resolution of subdural hematoma. MRI findings.
AB  - A 33-year-old man suffered a traumatic subdural hematoma with complete
      spontaneous resolution, as demonstrated by computed tomography scanning and
      magnetic resonance imaging. After resolution, there was obliteration of the
      subarachnoid space on the affected side, giving rise to relative dilation of the
      subarachnoid space over the uninvolved convexity. A resolved subdural hematoma
      should be considered in the differential diagnosis of such an asymmetry.

PMID- 9557154
TI  - Cerebello-thalamo-cerebral diaschisis: a case report.
AB  - This reports positron emission tomography and [18F]fluorodeoxyglucose (PET-FDG)
      in a 69-year-old woman who underwent resection of the left cerebellar hemisphere
      for an acoustic neurinoma 17 years earlier. Functional impairment in cerebral
      cortical and subcortical structures was evaluated by studying the level of
      glucose metabolic activity at rest. Relative glucose metabolism was reduced in
      the prefrontal cortex contralateral to the cerebellar lesion. Contralateral
      thalamic metabolism was reduced significantly. The results suggest that this
      phenomenon of "crossed cerebello-thalamo-cerebral diaschisis" is related to a
      functional depression of the cerebello-thalamo-cortical pathway.

PMID- 9557155
TI  - The alter ego of heat shock proteins.

PMID- 9557156
TI  - Screening for primary immunodeficiencies in the clinical immunology laboratory.

PMID- 9557157
TI  - Immunoglobulin- and hepatitis B surface antigen-specific circulating immune
      complexes in chronic hepatitis B virus infection.
AB  - For assessing the role of circulating immune complexes (CIC) in chronic hepatitis
      B virus (HBV) infection, CICs containing IgM, IgG, and HBsAg were determined by
      C1q and conglutinin (K) assays in 216 patients with chronic HBV infection and 54
      healthy controls. The concentration of each type of CIC in patients is higher
      than in controls (P = 0.0001). CIC is a common feature of chronic HBV infection
      with 95.8% of cases having at least one abnormal test result. At least one type
      of HBsAg-CIC is positive in 54.2% of patients. HBsAg-CIC positivity is associated
      with HBeAg positivity (P = 0.0001), higher aminotransferase levels (P < 0.002),
      and younger age (P = 0.001). IgG-CIC or IgM-HBsAg-CIC correlates with higher
      aminotransferase activity (P = 0.001). In conclusion, HBsAg-CIC correlates with
      HBV replication. IgG-CIC and/or IgM-HBsAg-CIC correlate with disease activity.
      Immune-mediated injury may play a role in the pathogenesis of chronic HBV
      infection.

PMID- 9557158
TI  - Expression of 70-kDa heat-shock protein during acute graft-versus-host disease.
AB  - Acute lethal graft-versus-host disease (GVHD) was induced in unirradiated (LEW x
      DA)F1 rats by injection of DA parental lymphoid cells. Control rats received the
      same dose of (LEW x DA)F1 cells. The level of hsp70 at different stages of GVHD
      was examined in the spleen, lymph nodes, thymus, liver, lung, kidney, heart, and
      skeletal muscles of GVHD and control animals. Hsp70 was present in all organs
      analyzed in both groups and, with the exception of the spleen and lymph nodes,
      detectable levels remained constant during the disease. However, the spleen and
      lymph nodes of GVHD rats showed distinct changes in the hsp70 levels throughout
      the course of the disease. Expression of hsp70 in spleen and lymph nodes was
      augmented 7 and 14 days after induction of the disease. During the last stages of
      GVHD, 18-21 days after the induction, expression of hsp70 diminished to a level
      similar to that in untreated and control animals. Elevated levels of hsp70 in
      lymphoid organs during GVHD suggest an involvement of hsp70 in the pathology of
      the disease.

PMID- 9557159
TI  - Characterization of the altered cutaneous reactivity of transgenic mice whose
      keratinocytes overexpress B7-1.
AB  - B7-1 (CD80) is a second signal molecule usually associated with "professional"
      APCs that prevents the induction of T-cell clonal anergy and induces IL-2
      production during antigen presentation. Tg mice whose epidermal KC overexpress B7
      1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to
      8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced
      ear-swelling responses to irritants that are not persistent. Exaggerated CHS was
      not reflected in the draining lymph node. T-lymphocyte proliferative responses
      after sensitization and local challenge with haptens, as there were no
      significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR
      analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg
      mice had an alteration in the kinetics of in situ lymphokine transcripts compared
      to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2
      weeks versus 24 h for NTg mice. RNase protection assays to detect inflammatory
      cytokine transcripts at hapten application sites indicated that B7-1 Tg mice
      responded to hapten application with increased TNF-alpha, IL-6, and TNF-beta
      transcripts compared to NTg mice. Thus, hapten-induced ear swelling in these Tg
      mice may be mediated by enhanced inflammatory cytokines during the early phase (1
      14 days). IFN-gamma-producing lymphocytes may be responsible for the late phase
      of the ear-swelling response (14-42 days). These data indicate that B7-1
      overexpression by KC in mouse skin directly or indirectly affects the nature of
      cutaneous inflammation induced by haptens and irritants.

PMID- 9557160
TI  - Influence of microbial stimulation on hypergammaglobulinemia and autoantibody
      production in pristane-induced lupus.
AB  - Pristane induces a lupus-like syndrome characterized by autoantibody production
      and glomerulonephritis in nonautoimmune strains of mice. Although it has been
      suggested that this syndrome results from nonspecific immune activation, there is
      little evidence so far that B cells are activated nonspecifically by pristane or
      that this promotes autoimmunity. In this study, we examined whether polyclonal
      hypergammaglobulinemia occurs in pristane-induced lupus, and its relationship to
      the production of anti-DNA, nRNP/Sm, and Su autoantibodies. In conventionally
      housed mice, there was a marked increase in total IgM and IgG3 2 weeks after i.p.
      pristane injection, followed by increased IgG1, IgG2a, and IgG2b levels. IgM
      levels were higher in pristane-treated specific pathogen-free (SPF) mice than in
      conventionally housed mice, whereas IgG and IgA levels were reduced. Pristane
      induced anti-nRNP/Sm and Su autoantibodies in SPF mice, but their onset was
      delayed and levels were lower than those in conventionally housed mice. There was
      no consistent relationship between total IgG1, 2a, and 2b hypergammaglobulinemia
      and production of anti-nRNP/Sm and Su autoantibodies. Moreover, the total Ig
      levels were similar in the anti-nRNP/Sm-positive and -negative groups. In
      contrast, production of IgM anti-ssDNA antibodies paralleled IgM
      hypergammaglobulinemia in some, but not all, mice. These studies indicate that
      pristane-induced lupus is associated with marked hypergammaglobulinemia, the
      magnitude of which is influenced by the microbial environment. However, anti
      nRNP/Sm and Su autoantibody production is at least partly independent of
      polyclonal B cell activation. The data strongly suggest that pristane-induced
      lupus is not exclusively the consequence of nonspecific immune stimulation. They
      also point to the importance of microbial stimulation in the development of
      hypergammaglobulinemia in this inducible lupus model.

PMID- 9557161
TI  - Taxol involution of collagen-induced arthritis: ultrastructural correlation with
      the inhibition of synovitis and neovascularization.
AB  - Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA)
      that can be regressed with Taxol (paclitaxel), a chemotherapeutic agent. To
      identify structural changes that occur with involution, the synovium from naive,
      untreated CIA, and Taxol-treated CIA rats were evaluated by light microscopy plus
      transmission and scanning electron microscopy. Analysis included detailed images
      of vascular networks using polymeric corrosion casts. The CIA synovium was
      morphologically similar to human RA synovium. In CIA, the integrity of the
      intimal lining is lost by Type-B synoviocytes becoming highly elongated and
      polarized toward the joint space, resulting in non-overlapping cellular processes
      and the elimination of the basal lamina. In addition, the lining expanded from a
      width of 6-10 microns in naives to 200-250 microns in CIA due primarily to
      increased numbers of both Type-A and -B synoviocytes and more interstitial
      matrix. Vascular corrosion casts of CIA synovium illustrated a marked increase in
      blood vessel volume and an extensive interconnecting vascular architecture;
      neovascular arrays were observed to project toward the synovial surface. In Taxol
      treated CIA, the synoviocyte and neovascular components reverted to the naive
      synovium morphology, suggesting that this agent might be useful in the therapy of
      RA.

PMID- 9557162
TI  - Is there IgA from gut mucosal origin in the serum of children with Henoch
      Schonlein purpura?
AB  - Thirty-two children with Henoch-Schonlein purpura with or without renal symptoms
      were studied to characterize the IgA hyperglobulinemia observed in the serum of
      most patients. It was shown that only the IgA1 subclass concentration was
      increased. Secretory IgA and IgA to gliadin levels were frequently increased in
      serum, with a good correlation between them. Circulating IgA immune complexes
      were detected often and contained high activity to gliadin. In contrast, IgA
      activity to tetanus toxoid did not change. We failed to show any differences in
      renal involvement. These data suggest that elevation of serum IgA in Henoch
      Schonlein purpura is due in part to a disturbance of the gut mucosal immune
      system, and the presence of circulating IgA immune complexes with dietary
      antigens can be postulated but cannot explain the occurrence of urinary symptoms.

PMID- 9557163
TI  - IL-10 production in common variable immunodeficiency.
AB  - Common variable immunodeficiency, (CVI) is a heterogeneous primary
      immunodeficiency disease in which there are T and B cell defects. Since IL-10 in
      conjunction with anti-CD40 promotes secretion of IgG, IgA, and IgM by CVI B
      cells, these studies were performed to investigate IL-10 production in CVI.
      Mitogen or anti-CD3 stimulated CVI peripheral blood mononuclear cells, or
      isolated T cells produced an insignificant amount of IL-10 over background
      levels. CVI monocyte IL-10 production was substantial and greater than that of
      normal controls. Anti-IL-10-neutralizing antibody strongly enhanced CVI T cell
      proliferative responses to PHA, but only to an insignificant extent, soluble
      antigens. IL-2 plus anti-IL-10 enhanced CVI proliferative responses to antigens
      significantly more over baseline than for cells of similarly tested normal
      controls. These data suggest that CVI T cell secretion of IL-10 is deficient, but
      that monocyte-derived IL-10, plus a relative lack of IL-2 production, could
      contribute to the defects of cell proliferation in this disorder.

PMID- 9557164
TI  - Identification of autoimmune thrombocytopenic purpura-related epitopes using
      phage-display peptide library.
AB  - A random heptapeptide phage-displayed library was screened with two serum samples
      from autoimmune thrombocytopenic purpura (AITP) patients to address the
      repertoire of autoantigenic epitopes involved in platelet destruction. We
      obtained a panel of affinity-selected phage clones that have been shown to react
      in enzyme-linked immunosorbent assay with autoantibodies from other AITP
      patients. None of the peptides obtained has been described previously as possibly
      being an epitope for antiplatelet antibodies, and the majority of them did not
      show any homology with known platelet glycoproteins. We conclude that peptides
      identified in this study could represent discontinuous epitopes or mimotopes of
      natural autoantigens. Also, they could be present in still-unknown proteins
      involved in AITP pathogenesis.

PMID- 9557165
TI  - Occupational asthma: prevention by definition.

PMID- 9557167
TI  - Chemicals in the workplace: incorporating human neurobehavioral testing into the
      regulatory process.
AB  - In February 1996, the United Kingdom Health and Safety Executive sponsored a
      workshop on the role of human neurobehavioral tests in the regulation of chemical
      exposures in the workplace. This paper presents the review of neurobehavioral
      testing that was initially prepared for the workshop but has been expanded and
      updated for publication. Information sources for the review were drawn from
      "preamble to the regulation," in the 1989 air contaminants project, an attempt by
      the Occupational Safety and Health Administration to update the 1968 regulatory
      limits of workplace exposures. The scientific citations listed in the preamble
      provide a chemical database to review for evidence of neurobehavioral testing to
      support limit setting. Several conclusions emerged: 1) A wide range of nervous
      system effects were reported in the scientific citations for the 172 chemicals
      identified with effects on the nervous system; 2) Citations of studies with human
      neurobehavioral test results are used to support limit setting, but many are old
      studies primarily of acute effects; 3) There is frequently a delay of several
      years after publication before studies with neurobehavioral testing are cited in
      regulatory forums; 4) With the 1989 proposed regulatory limits never legally
      adopted, there has not been an update for most of the substances affecting the
      nervous system since 1971; 5) Investigators should be more aware of the
      regulatory process and submit studies reporting neurobehavioral test results to
      organizations that regulate and recommend workplace exposure limits; 6) Issuances
      in the Federal Register by the U.S. Environmental Protection Agency provide a
      framework for assessing neurotoxic risks that can be used by investigators to
      help identify and report nervous system effects using neurobehavioral testing in
      a more uniform fashion.

PMID- 9557168
TI  - Occupational obstructive airway diseases in Germany.
AB  - In industrialized countries, occupational asthma caused by allergens and
      irritants due to workplace exposure is increasing. More than 8,000 such claims
      were made in Germany (10.5% of all decided occupational disease claims) in 1995;
      1,900 were confirmed (6.5% of all confirmed claims). The legal basis and the
      occupational disease-related regulations of trade-assigned statutory accident
      insurance institutions ('Berufsgenossenschaften') in Germany are described.
      Hitherto, three occupational disease categories for obstructive airway disorders
      existed: due to sensitizing agents, due to chemical-irritative or toxic agents,
      and due to isocyanates. Approximately 40% of accepted claims for occupational
      asthma and rhinitis result from exposure to flour. Ongoing changes in the
      recognition of work-related airway disease symptoms account for differences in
      the incidence and prevalence as reported over the years. Recently, chronic
      obstructive bronchitis and/or emphysema of hard coal miners have been included in
      the German list of occupational diseases.

PMID- 9557169
TI  - Airways inflammation and glucan exposure among household waste collectors.
AB  - A field study was made on 17 workers collecting unsorted household waste, eight
      workers collecting organic/nonorganic separated waste, and 24 controls.
      Measurements of airborne endotoxin and (1-->3)-beta-D-glucan were made in their
      working environments. Examinations consisted of a questionnaire for symptoms,
      spirometry, airway responsiveness, and blood and sputum sampling for
      determination of cell counts, eosinophilic cationic protein (ECP), and
      myeoloperoxidase (MPO). A higher proportion of waste collectors reported
      diarrhea, congested nose, and unusual tiredness as compared to controls. The
      number of blood lymphocytes was higher among waste collectors and were dose
      related to the amount of airborne (1-->3)-beta-D-glucan at the workplaces. The
      amount of ECP and the number of macrophages were lower in sputum among waste
      collectors as compared with controls. The results suggest that certain dusts from
      household waste may cause airway inflammation as well as general symptoms, and
      the effects were associated with higher (1-->3)-beta-D-glucan levels.

PMID- 9557166
TI  - Methodological considerations for the accurate determination of lead in human
      plasma and serum.
AB  - Studies which accurately measure plasma or serum lead (Pb) are needed to evaluate
      the 'biologically active' fraction of Pb in the circulation, and to clarify the
      role of plasma in the transportation of Pb between different compartments of the
      body. We evaluated several methodological aspects which influence the
      determination of Pb in plasma and serum. Generally, venous blood was obtained by
      different sampling methods (routine and ultraclean) from 3 subjects without
      history of Pb exposure. After centrifugation (800 g) for 10 min, the plasma or
      serum was analyzed by inductively coupled plasma-high-resolution mass
      spectrometry (ICP-MS). Several evaluations were conducted, including 1)
      comparison of an ultraclean serum collection method with a plasma collection
      method that used a commercial Vacutainer-type tube for trace metals (EDTA
      anticoagulant); 2) the effect of whole blood standing time prior to
      centrifugation on plasma or serum Pb concentration; and 3) comparison of a method
      using commercial heparinized Vacutainer tubes to an ultraclean plasma sampling
      method that utilized a low-Pb heparin anticoagulant. Plasma or serum iron (Fe)
      levels were also measured to evaluate hemolysis. The 3 subjects had whole blood
      Pb (blood-Pb) levels of 1.8, 2.0, and 2.7 micrograms/dl. Their corresponding
      ultraclean serum-Pb levels were 0.40%, 0.30%, and 0.48% of their whole blood-Pb
      levels, respectively. By comparison, the EDTA Vacutainer method plasma-Pb values
      were 1.7%, 1.5%, and 2.4% of whole blood-Pb, respectively. Whole blood standing
      (clotting) times of 15, 40, and 70 min before centrifugation resulted in
      increasing ultraclean serum-Pb levels of 0.21%, 0.81%, and 1.2% of whole blood-Pb
      (1.8 micrograms/dl), respectively. Whole blood standing time had no effect on
      plasma-Pb levels when heparin Vacutainers were used, or when a low-Pb heparin was
      used to obtain ultraclean plasma. However, plasma collected using the commercial
      heparin Vacutainer method contained consistently higher and more variable Pb
      levels than samples collected using the ultraclean plasma-Pb method. Hemolysis,
      when present, contributed significantly to both plasma-Pb and serum-Pb levels. In
      conclusion, plasma-Pb and serum-Pb levels are dependent upon methodologic
      processing techniques, including Pb contamination control, redistribution due to
      EDTA anticoagulant, hemolysis, and time dependency in sample processing. While
      true plasma-Pb and serum-Pb levels by any method have yet to be defined, these
      data provide a methodological basis from which to investigate variation in Pb
      partitioning between whole blood and plasma within individuals.

PMID- 9557170
TI  - Indirect assessment of 4,4'-diphenylmethane diisocyanate (MDI) exposure by
      evaluation of specific humoral immune responses to MDI conjugated to human serum
      albumin.
AB  - BACKGROUND: A study of occupational asthma among workers exposed to 4,4'
      Diphenylmethane Diisocyanate (MDI). OBJECTIVE: To demonstrate if serum
      concentrations of MDI-specific IgG or IgE are sensitive biological markers of
      disease or of MDI exposure. METHODS: The study group consisted of nine MDI
      exposed workers and nine nonexposed workers. Air sampling for MDI and
      polymethylene polyphenyl isocyanate, occupational and medical histories,
      respiratory physical exams, pre- and postshift spirometry, and self-administered
      peak expiratory flow rates were performed. Serum specific IgE and IgG antibodies
      to an MDI-human serum albumin (HSA) conjugate were assayed by the
      radioallergosorbent test and the enzyme-linked immunosorbent assay, respectively,
      and compared to nine nonexposed laboratory controls. RESULTS: No definitive cases
      of occupational asthma were documented. The mean level of MDI-specific IgG was
      significantly greater among exposed workers compared to nonexposed workers and
      laboratory controls (p = 0.04). Mean levels of TDI and HDI-specific IgG were also
      increased. CONCLUSION: This study demonstrates that serum concentrations of MDI
      specific IgG appear to be a moderately sensitive biological marker of MDI
      exposure, but not an indicator of occupational asthma. Workers with IgG
      antibodies specific for one diisocyanate-HSA conjugate exhibit cross-reactivity
      to antigens prepared with other diisocyanates.

PMID- 9557171
TI  - Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose
      rayon fibers factory.
AB  - The exposure-excretion relationship to carbon disulfide (CS2) vapor in 407
      exposed workers was studied during the second half of the working week. Carbon
      disulfide concentrations were also determined in 50 nonexposed subjects. The
      geometric mean value for CS2 in urine samples from the latter was: 0.23
      microgram/l (95% upper limit = 0.52 microgram/l) when log-normal distribution was
      assumed. Among the exposed workers, the CS2 level in urine samples collected
      after the first half shift exceeded the 95% upper limit of nonexposed subjects in
      every case. The time-weighted average intensity of exposure to CS2 vapor was
      measured using personal diffusive samplers (in which carbon cloth served as an
      adsorbent). CS2 concentrations in urine were determined in samples collected at
      the end of the first half shift from the 407 exposed cases as well as from 50
      nonexposed controls. There was a significant correlation (p < 0.0001) between the
      exposure to CS2 vapor at concentrations of up to 64 mg/m3 and the levels of CS2
      measured in the urine samples after four hours of exposure. The correlation
      indicated that a mean level of 15.5 micrograms CS2/l urine (95% confidence range,
      13.8-17.1 micrograms/l) was excreted following an exposure to CS2 at 31 mg/m3
      (the current occupational exposure limit).

PMID- 9557172
TI  - Workplace violence at government sites.
AB  - A government agency and its contractors employing nearly 96,000 workers
      throughout the country was surveyed for documented incidents of violence in the
      workplace. Thirty-five occupational medicine and related professionals (36% of
      those surveyed) from 27 locations returned the questionnaire. Of the responders,
      20 individuals reported 74 incidents of workplace violence, with nearly 30% of
      these occurrences involving weapons, including 11 with guns. In a companion
      survey of human resource departments from 28 locations, there were 16 responders
      (57% of those surveyed) with 13 of them documenting 96 additional incidents. No
      duplicate reporting of the same event occurred between the two surveys.
      Approximately 70% of the agency workers were employed in locations covered by the
      51 responders. Although the data are limited, the number of incidents and level
      of violence appear to be increasing over time. Of the 108 incidents for which
      time of occurrence was known, 32 were defined as "very serious," which included
      physical assault, threat or assault with a weapon, murder, suicide, or stalking.
      Verbal threats, verbal assaults, and vandalism were defined as "serious"
      incidents. A Cochran-Armitage trend test for an increasing proportion over time
      of "very serious" vs. "serious" events was statistically significant, with a P
      value of 0.026.

PMID- 9557173
TI  - Impact of managers' personal determinants in notifying workplace hazards.
AB  - Notification about work hazards is a legal requirement in advanced industrial
      countries, but workers have claimed, that in many cases, they do not receive
      enough information regarding risks, exposure, and medical problems. The recent
      professional literature on the subject has explored the ways in which
      notification is delivered without sufficiently considering the psychological
      incentives and barriers that may affect managers in transmitting risk
      information. The present study aimed at examining managers' personal determinants
      and notification of work hazards in a sample of 106 managers and 460 workers in
      40 departments of three industrial plants in Israel. Results of our study showed
      that both managers and workers perceived the importance of the delivery of safety
      information as quite high (means of 3.43 and 3.7, respectively, out of 5), with
      managers reporting that they rely primarily on personal modes of communication.
      Immediate supervisors were regarded by both groups as the most important persons
      in notification. Managers having past experience in treating injured workers
      notified more, primarily using personal notification. The most important personal
      determinants that positively predicted managers' notification were their sense of
      self-efficacy and positive expectation of notification. Outcome denial and coping
      by distancing were negatively correlated with notifying about these risks.

PMID- 9557174
TI  - Women who quit maquiladora work on the U.S.-Mexico border: assessing health,
      occupation, and social dimensions in two transnational electronics plants.
AB  - This cohort study of 725 women examined the health, occupational, and social
      factors that contribute to quitting work in two transnational electronics
      maquiladoras (assembly plants) in Tijuana, Mexico. The estimated cumulative
      probabilities of quitting were 68% and 81% by 1 and 2 years of employment. After
      adjusting for other factors, women who had a history of smoking or surgery and
      those who returned to work after a paid leave due to illness were more likely to
      quit. In contrast, women with a history of chronic illness had lower quitting
      rates. The nationality of the company and the work shift also significantly
      influenced quitting rates, but demographic characteristics and health care visits
      did not have a significant effect. Women selectively leave maquiladora
      employment, often due to health-related events. The healthy worker effect is
      difficult to measure in a mobile population with high turnover.

PMID- 9557175
TI  - Work-related injuries among Iowa farm operators: an analysis of the Iowa Farm
      Family Health and Hazard Surveillance Project.
AB  - In 1994, the Iowa Farm Family Health and Hazard Surveillance Project carried out
      a two-stage, stratified, cluster survey of Iowa farms using a mail survey. With
      data from this representative sample of Iowa farmers, we examined the
      associations between farm-work-related injuries and possible risk factors for 390
      principal farm operators. Forty (10.3%) of these operators reported being injured
      while doing farm work. We developed a logistic regression to assess associations
      between potential risk factors and injury. We found three factors significantly
      associated with injury: younger age (odds ratio [OR] = 3.1, confidence interval
      [CI] = 1.1-9.3), having an impairment or health problem that limits work (OR =
      2.4, CI = 1.5-3.8), and hand or arm exposure to acids or alkalis (OR = 2.6, CI =
      1.1-5.9). In the univariate analysis, safety training did not seem to protect
      farmers from injuries.

PMID- 9557176
TI  - [Treatment of primary hyperhidrosis: a new indication for video thoracoscopy].

PMID- 9557177
TI  - [Training of inspiratory muscles in chronic obstructive lung disease. Its impact
      on functional changes and exercise tolerance].
AB  - The aim of this study was to evaluate the impact of inspiratory muscle training
      on lung function and exercise tolerance in patients with chronic obstructive
      pulmonary disease (COPD). Thirty-five patients with stable COPD were enrolled. We
      measured lung function variables and peak inspiratory and expiratory pressures
      (PImax and PEmax). Tests of progressive maximal exercise tolerance and stable
      submaximal exercise tolerance were administered. Two study groups were formed.
      Group A patients (n = 20) were enrolled in a respiratory muscle training program
      lasting four months. Group B (n = 15) was the control group. At the end of the
      study period the patients underwent testing similar to the first battery of
      tests. All showed moderate to severe obstruction with no significant differences
      between groups (FEV1: group A 37.6 +/- 13%, group B 36.6 +/- 12%; FVC: group A
      80.4 +/- 15%, group B 80 +/- 12%). Nor were there any significant differences
      between the two groups in initial results of either maximal respiratory pressures
      or exercise tolerance. No lung function changes were observed in either group.
      PImax in group A increased significantly at the end of the study (from 54 +/- 9
      to 78 +/- 16 cmH2O; p < 0.001); there were no changes in group B. No changes were
      seen in VO2max or ventilatory response and/or gasometry during exercise in any of
      the groups. The trained group, on the other hand, experienced a significant
      decrease in dyspnea evaluated on the Borg scale exercise in maximal (5.7 +/- 1.1
      versus 4.7 +/- 1.2, p < 0.005) and submaximal (5.9 +/- 0.9 versus 4.9 +/- 1.3, p
      < 0.005) and an increase in time of submaximal exercise tolerance (5.5 +/- 2
      versus 7 +/- 3 min, p < 0.05), changes that were not observed in the control
      group. Based on these results, and although specific training of inspiratory
      muscles does not appear to improve lung function in patients with COPD, it is
      accompanied by a decreased sense of dyspnea during exercise and greater
      tolerance.

PMID- 9557178
TI  - [Bronchial carcinoid tumors: a prospective study].
AB  - We report the results of a study performed in the thoracic surgery department of
      Hospital General Universitario of Valencia from October 1989 to December 1996. Of
      the 621 patients diagnosed of lung cancer during this period, 320 underwent the
      usual surgical excision, 18 were confirmed histologically as bronchial carcinoid
      tumors, indicating an incidence of 5.6% of all pulmonary neoplasms resected in
      our department. The symptoms most often reported were recurring infection (44.5%)
      and chest pain (33.3%). Only one patient presented carcinoid syndrome. The most
      common radiologic presentation was solitary pulmonary nodule (50%). The tumor was
      visible by fiberoptic bronchoscopy in 9 cases. Diagnosis was by bronchial biopsy
      in four cases. Confirmation was by immunohistochemical analysis of the specimen
      in all cases. Electron microscopy and immunohistochemical techniques using
      neuroendocrine panmarkers is considered fundamental for differentiating between
      neuroendocrine neoplasms and typical and atypical carcinoid tumors. Thirteen
      (72.2%) of the 18 patients studied were diagnosed of typical carcinoids and 5
      (27.8%) of atypical carcinoids. Neuroendocrine marking showed neurospecific
      enolase in 15 patients and chromogranin positivity in 10.

PMID- 9557179
TI  - [Guidelines for indications and use of domiciliary continuous oxygen (DCO)
      therapy. SEPAR guidelines].

PMID- 9557180
TI  - [Drug treatment of pulmonary tuberculosis in the 19th century].

PMID- 9557181
TI  - [Solitary adrenal metastasis of pulmonary cancer].
AB  - We describe the case of a 46-year-old man with lung cancer and simultaneous
      solitary adrenal metastases. Adrenalectomy was performed 12 weeks after lung
      resection through a right subcostal laparotomy. Treatment was complemented with
      chemotherapy. Twelve months after adrenalectomy the patient was found free of
      signs of disease and was in satisfactory condition. The advantages of and
      indications for surgical resection of suprarenal metastasis are discussed in the
      light of published literature. In some cases, survival may improve with exeresis
      and chemotherapy.

PMID- 9557182
TI  - [Endobronchial metastasis of uterine leiomyosarcoma].

PMID- 9557183
TI  - [Article by Rubia et al., "The evaluation of lung vascular compliance by the
      dobutamine stress test in patients who are candidates for extensive lung
      resections"].

PMID- 9557184
TI  - [Management of pleural effusion].

PMID- 9557185
TI  - Red lipstick: a source of barium to humans and the environment.

PMID- 9557186
TI  - Aqueous phase ethylation atomic emission spectroscopy for the determination of
      methylmercury in fish using permeated dimethylmercury calibration.

PMID- 9557187
TI  - Shaker bath adaptation to the Environmental Protection Agency's cadmium column
      reduction method (method 353.3) for the determination of nitrate in water
      samples.

PMID- 9557188
TI  - Effects of monitor well purging technique on selected chemical properties of
      surficial groundwater.

PMID- 9557189
TI  - Trace metals in moose (Alces alces) liver.

PMID- 9557190
TI  - Metals and organochlorine compounds in fish from Latvian lakes.

PMID- 9557191
TI  - Distribution of heavy metal residues in some tissues of Caretta caretta
      (Linnaeus) specimen beached along the Adriatic Sea (Italy).

PMID- 9557192
TI  - Heavy metals in sediments from Coatzacoalcos River, Mexico.

PMID- 9557193
TI  - Avian exposure to pesticides in Costa Rican banana plantations.

PMID- 9557194
TI  - Influence of spray adjuvants on the behavior of trifluralin in the soil.

PMID- 9557196
TI  - Long-term DDT pollution in tropical soils: effect of DDT and degradation products
      on soil microbial activities leading to soil fertility.

PMID- 9557195
TI  - Isoxaflutol herbicide soil persistence and mobility in summer corn and winter
      wheat crops.

PMID- 9557197
TI  - Removal of malathion residues on lettuce by washing.

PMID- 9557198
TI  - Chlorpyriphos, quinalphos, and lindane residues in sesame seed and oil (Sesamum
      indicum L.).

PMID- 9557199
TI  - Occurrence of three pesticides in community water supplies, Kenya.

PMID- 9557200
TI  - Environmental estrogens in agricultural drain water from the central valley of
      California.

PMID- 9557201
TI  - Mutagenicity of river water in Korea.

PMID- 9557202
TI  - Transplacental transfer of asbestos in pregnant mice.

PMID- 9557203
TI  - Hyperglycemia induced in rabbits exposed to ochratoxin.

PMID- 9557204
TI  - Acute administration of methylmercury changes in vivo dopamine release from rat
      striatum.

PMID- 9557205
TI  - Cadmium-induced scale deformation in carp (Cyprinus carpio).

PMID- 9557206
TI  - Azinphosmethyl exposure to grass shrimp (Palaemonetes pugio) life stages with
      emphasis on larval acetylcholinesterase activity.

PMID- 9557207
TI  - Selective growth inhibition of the musty-odor producing cyanobacterium
      Oscillatoria cf. chalybea by natural compounds.

PMID- 9557208
TI  - Exposure of juvenile rainbow trout (Oncorhynchus mykiss) to methoxychlor results
      in a dose-dependent decrease in growth and survival but does not alter male
      sexual differentiation.

PMID- 9557209
TI  - Environmental endocrine modulators and human health: an assessment of the
      biological evidence.
AB  - Recently, a great deal of attention and interest has been directed toward the
      hypothesis that exposure, particularly in utero exposure, to certain
      environmental chemicals might be capable of causing a spectrum of adverse effects
      as a result of endocrine modulation. In particular, the hypothesis has focused on
      the idea that certain organochlorine and other compounds acting as weak estrogens
      have the capability, either alone or in combination, to produce a variety of
      adverse effects, including breast, testicular and prostate cancer, adverse
      effects on male reproductive tract, endometriosis, fertility problems,
      alterations of sexual behavior, learning disability or delay, and adverse effects
      on immune and thyroid function. While hormones are potent modulators of
      biochemical and physiological function, the implication that exposure to
      environmental hormones (e.g., xenoestrogens) has this capability is uncertain.
      While it is reasonable to hypothesize that exposure to estrogen-like compounds,
      whatever their source, could adversely affect human health, biological
      plausibility alone is an insufficient basis for concluding that environmental
      endocrine modulators have adversely affected humans. Diethylstilbestrol (DES) is
      a potent, synthetic estrogen administered under a variety of dosing protocols to
      millions of women in the belief (now known to be mistaken) that it would prevent
      miscarriage. As a result of this use, substantial in utero exposure to large
      numbers of male and female offspring occurred. Numerous studies have been
      conducted on the health consequences of in utero DES exposure among the adult
      offspring of these women. There are also extensive animal data on the effects of
      DES and there is a high degree of concordance between effects observed in animals
      and humans. The extensive human data in DES-exposed cohorts provide a useful
      basis for assessing the biological plausibility that potential adverse effects
      might occur following in utero exposure to compounds identified as environmental
      estrogens. The effects observed in both animals and humans following in utero
      exposure to sufficient doses of DES are consistent with basic principles of dose
      response as well as the possibility of maternal dose levels below which potential
      non-cancer effects may not occur. Significant differences in estrogenic potency
      between DES and chemicals identified to date as environmental estrogens, as well
      as an even larger number of naturally occurring dietary phytoestrogens, must be
      taken into account when inferring potential effects from in utero exposure to any
      of these substances. The antiestrogenic properties of many of these same
      exogenous compounds might also diminish net estrogenic effects. Based on the
      extensive data on DES-exposed cohorts, it appears unlikely that in utero exposure
      to usual levels of environmental estrogenic substances, from whatever source,
      would be sufficient to produce many of the effects (i.e., endometriosis, adverse
      effects on the male reproductive tract, male and female fertility problems,
      alterations of sexual behavior, learning problems, immune system effects or
      thyroid effects) hypothesized as potentially resulting from exposure to chemicals
      identified to date as environmental estrogens.

PMID- 9557211
TI  - IL-1 receptor antagonist gene polymorphism in patients with secondary acute
      myeloid leukaemia.
AB  - Acute myeloid leukaemia (AML) may not only occur as a de novo disease but may
      evolve from a preceding myelodysplastic syndrome (MDS) or may result from therapy
      for a previous malignancy. These secondary acute myeloid leukaemias (sAML)
      possess some common biological and clinical features of the corresponding de novo
      disorders. The cytokine interleukin-1 (IL-1) is known to have a role in
      haematopoiesis, and modulation of its action might contribute to the deregulation
      of proliferation seen in leukaemia. It has recently been reported that a variable
      number tandem repeat (VNTR) polymorphism in the IL-1 receptor antagonist (IL-1ra)
      gene is closely associated with the severity of many inflammatory and autoimmune
      diseases, and may also play a role in the pathogenesis of sAML. We sought to
      confirm this finding in a large group of patients classified as having sAML. We
      found no differences in either the genotypic or allele frequencies of the
      polymorphism studied when compared with those of normal controls or other
      haematological disorders. No differences were observed in allele frequencies
      between younger and older patients, or between those patients who had an
      antecedent myelodysplasia and those who had received prior chemotherapy or
      radiotherapy. We conclude that the described polymorphism in the IL-1ra gene is
      not associated with the development of sAML.

PMID- 9557210
TI  - Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem
      cell transplantation: a clinical pilot study.
AB  - Allogeneic cell therapy (allo-CT) is emerging as an effective treatment for
      patients relapsing after allogeneic bone marrow transplantation (BMT), indicating
      that tumor cells resisting chemoradiotherapy may still respond to immunocompetent
      allogeneic lymphocytes. We investigated possible graft-versus-tumor (GVT) effects
      in six patients with metastatic breast cancer that would be comparable to the
      graft-versus-leukemia (GVL) phenomenon occurring after allogeneic BMT in
      hematologic malignancies. The patients were cytoreduced with high-dose
      chemotherapy and autologous stem cell transplantation (ASCT), and were treated
      ambulatory with allo-CT consisting of adoptive transfer of HLA-matched donor
      peripheral blood lymphocytes (PBL) activated in vivo with human recombinant
      interleukin-2 (rIL-2). If no graft-versus-host disease (GVHD) developed, allo-CT
      was augmented with infusion of donor PBL, preactivated in vitro with rIL-2.
      Treatment was well tolerated, with low therapy-related toxicity in all patients.
      Two patients developed signs and symptoms compatible with GVHD grade I-II, one of
      whom shows no evidence of disease at more than 34 months out. In the remaining
      patients, progression-free survival following allo-CT ranged between 7 and 13
      months. Allogeneic cell-mediated, cytokine-activated immunotherapy might be
      utilized for induction of GVT in metastatic breast cancer. A search for
      techniques to boost chimerism without severe GVHD is indicated.

PMID- 9557212
TI  - Inhibitory effect of interleukin-10 on human leukocyte interferon-alpha
      production by Sendai virus.
AB  - Treatment of human peripheral blood leukocytes (hPBL) with Sendai virus induces
      significant production of human interferon-alpha (IFN-alpha). Addition of human
      recombinant interleukin-10 (IL-10) to hPBL in vitro prior to treatment with
      Sendai virus resulted in considerable inhibition of IFN-alpha production.
      Downregulation of IFN-alpha production was IL-10 concentration-dependent and
      observed at IL-10 concentrations of as low as 0.05 ng/ml, with a median effective
      dose (ED50) of about 5 ng/ml. Inhibition of IFN-alpha production by IL-10
      occurred at an early stage of Sendai virus induction. The inhibitory effect of IL
      10 on leukocyte interferon production was specific and blocked by pretreatment
      with neutralizing polyclonal anti-IL-10 antibody. This downregulatory effect is
      at the transcriptional level, since IL-10 inhibits IFN-alpha mRNA accumulation
      upon Sendai virus treatment. These data suggest that leukocyte IFN-alpha
      production is a highly regulated process that is modulated by cytokines such as
      IL-10 during early immunological response to infection.

PMID- 9557213
TI  - Open-label phase I study of combination therapy with zidovudine and interferon
      beta in patients with AIDS-related Kaposi's sarcoma: AIDS Clinical Trials Group
      Protocol 057.
AB  - The aim of this study was to identify a safe and tolerable dose of recombinant
      interferon-beta (IFN-beta) used in conjunction with a fixed dose of zidovudine in
      patients with early-stage, good-prognosis AIDS-related Kaposi's sarcoma. We
      conducted a phase I, dose-escalation controlled trial of 22.5, 45 of 90 million
      units of IFN-beta given by daily subcutaneous injection with 500 mg per day of
      oral zidovudine. At the time of this study, this was standard of care for HIV
      infection. Patients were sequentially enrolled at three medical centers. Tumor
      response, drug tolerance, antiviral studies and CD4 changes were assessed. Four
      patients were enrolled at each dose level, and escalation proceeded when at least
      four patients had tolerated two weeks of therapy without dose-limiting toxicity.
      ACTG Kaposi's sarcoma tumor response criteria were used to assess response.
      Fifteen patients were enrolled. The combination of IFN-beta and zidovudine was
      well tolerated, and the dose-limiting toxicities were local skin necrosis and
      systemic symptoms. Despite generally good prognostic characteristics, only two
      patients achieved a clinical complete response and three addition patients had
      stable disease for a prolonged period of time (range 24-44 weeks). There was no
      correlation between baseline CD4 cell counts and tumor response, nor between the
      antiviral effect of IFN-beta as measured by decreases in immune-complex
      dissociated p24 antigen and tumor response. Higher doses of IFN-beta did not
      result in more tumor responses or in greater antiviral activity. The maximum
      tolerated dose of IFN-beta in combination with 500 mg per day of zidovudine was
      45 million units by subcutaneous injection per day. IFN-beta is well tolerated in
      patients with AIDS-related Kaposi's sarcoma when used in conjunction with
      zidovudine. However, the antitumor response rate in good-prognosis patients is
      low. Further studies of this agent should be in the context of four-drug
      antiretroviral regimens where viral suppression is greatest and any antitumor
      activity of IFN-beta may be observed.

PMID- 9557214
TI  - Thrombopoietin in vitro and in vivo.
AB  - The characterization of the c-Mpl receptor resulted from studies on a murine
      retrovirus, and proved an important step in the identification of a key
      hemopoietic regulator. First proposed and named in 1958, the ultimate
      characterization of the long-awaited 'thrombopoietin' (TPO) came with the
      molecular cloning and characterization of the in vitro and in vivo properties of
      the c-Mpl ligand. Gene targeting experiments have demonstrated that the TPO/Mpl
      receptor signalling pathway is the principal physiological regulator of
      megakaryocytes and platelets. Analysis of signalling through c-Mpl has provided
      important insights into the function of this pathway, which, as with other
      members of the hemopoietin receptor family, involves activation of the JAK/STAT
      and Ras signalling cascades. Preclinical studies have documented a role for this
      molecule in overcoming thrombocytopenia following chemo/radiotherapy in several
      animal models. Clinical studies have demonstrated the safety and efficacy of Mpl
      ligand in elevating platelet counts. The identification of thrombopoietin has
      provided an important impetus in understanding megakaryocyte and platelet
      physiology, and provided a new therapeutic that will find application in a
      variety of clinical contexts.

PMID- 9557215
TI  - Immunotherapy of cancer using dendritic cells.
AB  - While the promise of harnessing the immune system for a therapeutic effect has
      remained largely unfulfilled for many years, the discovery of the central role of
      dendritic cells in stimulating antigen-specific immune responses has prompted new
      enthusiasm for immunotherapy of malignancies. Elucidation of the pathways of
      dendritic cell development and trafficking, acquisition and processing of
      antigen, and stimulation of T cells has suggested methods for generating and
      antigen-loading dendritic cells for use in immunotherapy protocols. Animal models
      have demonstrated that dendritic cells can stimulate protective antitumor
      responses in vivo. Phase I clinical trials have been initiated to address the
      safety and feasibility of immunizations with dendritic cells in humans with
      various malignancies.

PMID- 9557216
TI  - Molecular mechanisms of pancreatic beta-cell destruction in autoimmune diabetes:
      potential targets for preventive therapy.
AB  - Mononuclear cell infiltration into the islets of the pancreas (insulitis) is
      characteristic of autoimmune diabetes. T lymphocytes are the predominant
      subpopulation seen in insulitis, and are involved in the autoimmune process.
      Insulin-producing beta cells are thought to be destroyed by cytotoxic T cells,
      cytokines or nitric oxide, and beta-cell death occurs, at least partly, via
      apoptosis. Beta-cell death induced by cytokines is inhibited by Bcl-2, suggesting
      its potential as a tool for gene therapy. The Fas/Fas-ligand system plays a
      critical role in inducing insulitis and overt diabetes in nonobese diabetic (NOD)
      mice, a model of autoimmune diabetes. T-cell receptor gene usage in infiltrating
      T cells is not restricted in NOD mice, but there are some observations indicating
      relative restriction in human IDDM patients. Preventive strategies might be
      developed by focusing on these molecules involved in beta-cell destruction. The
      establishment of screening techniques for detecting prediabetic patients is also
      necessary to allow successful intervention.

PMID- 9557217
TI  - Active specific T-cell-based immunotherapy for cancer: nucleic acids, peptides,
      whole native proteins, recombinant viruses, with dendritic cell adjuvants or
      whole tumor cell-based vaccines. Principles and future prospects.
AB  - Whereas tumor cells are poor immunogens, recombinant tumor cells or dendritic
      cells as well as engineered viruses have been demonstrated to elicit specific
      antitumor immune responses leading to tumor growth suppression and long-lasting
      immunity in mouse tumor models. Single cytotoxic T lymphocyte-defined epitope
      based strategies have proved useful for immunization in tumor-bearing mice. This
      strategy is under investigation in human melanoma, along with adjuvants such as
      cytokines or dendritic cells. Flt3L is an in vivo dendritic-cell growth factor
      that offers new prospects in the field of active specific immunotherapy. These
      immunotherapeutic approaches are being tested in clinical trials, and may open up
      novel avenues for disease-free patients with poor prognostic factors.

PMID- 9557218
TI  - The sebaceous gland and acne--40 years on.

PMID- 9557219
TI  - The organ-maintained human sebaceous gland.
AB  - In the absence of epidermal growth factor (EGF) and phenol red in the maintenance
      medium, human sebaceous glands apparently retain in vivo rates of cell division
      and lipogenesis over 7 days and also retain in situ morphology. This is
      reversible on the re-addition of 10 ng/ml EGF and 10 mg/ml phenol red. The
      addition of 600 pM 17 beta-oestradiol results in a significant fall in the rate
      of lipogenesis over 7 days' maintenance, without affecting the rate of cell
      division. This effect is apparently due to abnormal differentiation of newly
      formed sebocytes. Neither 1 nM testosterone nor 1 nM dihydrotestosterone has any
      effect on rates of cell division or lipogenesis over 7 days. 1 microM 13-cis
      retinoic acid causes a significant reduction in the rate of lipogenesis over 7
      days.

PMID- 9557220
TI  - The human sebocyte culture model provides new insights into development and
      management of seborrhoea and acne.
AB  - Seborrhoea and acne are exclusively human diseases and sebaceous gland
      differentiation is species specific. Therefore, fundamental research on human
      sebaceous cell function and control requires human in vitro models. The human
      sebocyte culture model, introduced in 1989, has been used in several studies to
      elucidate sebaceous gland activity and its regulation at the cellular level.
      Cultured human sebocytes have been shown to preserve important sebocytic
      characteristics, although they undergo an incomplete terminal differentiation in
      vitro. In vitro synthesis of free fatty acids without bacterial involvement and
      marked interleukin 1 alpha expression at the mRNA and protein levels with no
      further induction by lipopolysaccharides lead to the assumption that human
      sebocytes may initiate acne lesions by an intrinsic mechanism. Androgens affected
      sebocyte activity in vitro in a manner dependent on the localization of the
      sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens
      could be completely abolished by spironolactone. Cultured sebocytes strongly
      expressed type 1 5 alpha-reductase and metabolized testosterone to
      androstenedione, 5 alpha-androstanedione, 5 alpha-dihydrotestosterone,
      androsterone and 5 alpha-androstanediol, whereas the levels of 5 alpha-reductase
      activity were probably not feedback regulated. 4,7 beta-Dimethyl-4-aza-5 alpha
      cholestan-3-one, a type 1 5 alpha-reductase inhibitor, induced an early, marked
      down-regulation of 5 alpha-reductase activity in human sebocytes in vitro, while
      hydrofinasteride, a type 2 inhibitor, required 10(3)-fold higher concentrations
      to induce similar effects. Stimulation of sebocyte proliferation by insulin,
      thyroid-stimulating hormone and hydrocortisone indicates that the hormonal
      control of the sebaceous gland could be a complex mechanism. Retinoids inhibited
      sebocyte proliferation in a dose-dependent manner and down-regulated lipid
      synthesis and sebocyte differentiation in vitro. Isotretinoin was the most potent
      compound. On the other hand, vitamin A was found essential for sebocyte activity
      and differentiation in vitro and could be partially substituted by synthetic
      retinoids. The inhibitory effect of isotretinoin on sebocyte proliferation was
      barely affected by the presence of vitamin A. The low persistent isotretinoin
      levels or, more likely, the considerably elevated tretinoin concentrations
      detected in human sebocytes after treatment with isotretinoin in vitro may be
      responsible for the inhibitory effect of this compound on sebocyte activity.

PMID- 9557221
TI  - Modelling the infundibulum in acne.
AB  - The human sebaceous-pilosebaceous infundibulum was isolated and maintained for 7
      days. Infundibular viability was maintained over 7 days in this medium. The
      addition of 1 ng/ml interleukin 1 alpha (IL-1 alpha) caused hypercornification of
      the infundibulum similar to that seen in comedones which could be blocked by
      1,000 ng/ml IL-1 receptor antagonist. However, in contrast to interferon gamma 1,
      IL-1 alpha had no effect on the expression of intercellular adhesion molecule or
      human leucocyte antigen type DR in infundibular keratinocytes. The addition of 5
      ng/ml epidermal growth factor or 5 ng/ml transforming growth factor alpha to the
      medium caused a disorganization of the keratinocytes of the infundibulum. We are
      now, therefore, able to model histologically the major infundibular changes in
      acne. Furthermore, we suggest that IL-1 alpha causes the scaling seen in many
      inflammatory skin diseases.

PMID- 9557222
TI  - Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the
      infrainfundibulum of subjects with and without acne vulgaris.
AB  - Linoleic acid deficiency, interleukin 1, retinoids and androgens have been
      implicated as causative factors in the follicular hyperkeratinization seen in
      acne. The goal of this study was to test the hypothesis that more androgens are
      produced in follicles of acne subjects compared to subjects without acne. Thirty
      four subjects (males and females with and without acne) were studied. The
      activity of 5 alpha-reductase (5 alpha-R) and 17 beta-hydroxysteroid
      dehydrogenase (17 beta-HSD) was determined in keratinocytes cultured from the
      infrainfundibulum and epidermis. Mean enzyme activities were slightly higher in
      the acne groups compared to the groups without acne, but differences were not
      statistically significant, perhaps due to limitations of this in vitro model. The
      activity of both 5 alpha-R and 17 beta-HSD was significantly greater in
      infrainfundibular keratinocytes compared to epidermal keratinocytes in all
      subject groups. 17 beta-HSD activity was 2.5- to 7-fold greater than the activity
      of 5 alpha-R in infrainfundibular keratinocytes. The regulation of 17 beta-HSD by
      endogenous factors may be important in determining the directional activity of 17
      beta-HSD and hence the local concentration of testosterone within the
      infrainfundibulum. Additional studies of the effects of androgens on follicular
      keratinization are needed.

PMID- 9557223
TI  - Mechanisms of androgen induction of sebocyte differentiation.
AB  - It has been difficult to induce the expected sebocyte differentiation in vitro
      with dihydrotestosterone (DHT). We reasoned that our culture system lacks
      differentiating factors, and peroxisome proliferator-activated receptors (PPARs)
      were the prime candidates. We tested PPAR activators informative about diverse
      PPAR subtypes, with and without DHT (10(-6) M): BRL-49653 (10(-6) M, PPAR-gamma),
      WY-14643 (10(-6) M, PPAR-alpha), and linoleic acid (LIN, 10(-4) M, PPAR-delta).
      Treatments were added in serum-free medium to cultures of rat preputial
      sebocytes. Control, DHT, BRL and BRL + DHT treatments caused 11, 25, 66 and 80%,
      respectively, of preputial cell colonies to differentiate into lipid-forming
      colonies (LFCs) (p < 0.001). WY induced 20% and LIN over 95% LFC formation. PPAR
      gamma mRNA was identified in preputial sebocytes by the RNase protection assay.
      These data suggest that differentiation of sebocytes is transduced by PPARs and
      have implications for the development of new treatments for acne.

PMID- 9557224
TI  - The isolation and characterization of androgen-dependent genes in the flank
      organs of golden Syrian hamsters.
AB  - To elucidate the molecular action of androgens, we have isolated two androgen
      dependent genes, FAR-17a and -17c, from the cDNA library of flank organs of male
      golden Syrian hamsters by a differential hybridization method. FAR-17a has been
      reported previously. Androgens regulated the expression in the flank organs, ear
      lobe and skin. FAR-17a protein was located in sebaceous glands. FAR-17c has a
      similar expression pattern to that of FAR-17a, but its response to androgen is
      faster than that of FAR-17a. It is expressed strongly in the liver, sebaceous
      glands and brain. The homology search and mRNA expression pattern suggested that
      it might encode a stearyl CoA desaturase (SCD) of golden Syrian hamsters. The SCD
      is a key enzyme in fatty acid biosynthesis and its expression is controlled by
      temperature, nutritional conditions and hormones. This is the first report that
      the mRNA expression of stearyl CoA is regulated by androgens.

PMID- 9557225
TI  - Heterogeneity and quantitative differences of type 1 5 alpha-reductase expression
      in cultured skin epithelial cells.

PMID- 9557226
TI  - Incidence of increased androgen levels in patients suffering from acne.

PMID- 9557227
TI  - Propionibacterium acnes colonization in acne and nonacne.
AB  - Propionibacterium acnes is a number of the resident bacterial flora and resides
      in sebaceous follicles. Age-related and body-dependent quantitative differences
      exist, indicating the role of sebum as an important ecological factor for P.
      acnes. Acne patients demonstrate marked increases in this organism which
      generates inflammation through a variety of mechanisms.

PMID- 9557228
TI  - Bacterial resistance in acne.
AB  - Antibiotics play a major role in acne therapy. Physicians base treatment choices
      on personal perceptions of efficacy, cost-effectiveness or risk-benefit ratios
      and rarely take bacterial resistance into account. It is well documented that
      resistant strains of coagulase-negative staphylococci within the resident skin
      flora increase in both prevalence and population density as duration of therapy
      increases. Acne patients represent a considerable reservoir of resistant strains
      of these important nosocomial pathogens which can be transferred to close
      contacts. Resistance in cutaneous propionibacteria has received scant attention
      in view of the central role of Propionibacterium acnes in inflammatory acne.
      Isolates resistant to one or more anti-acne antibiotics (most commonly
      erythromycin) have been reported in Europe, the USA, Japan and New Zealand.
      Carriage of resistant strains results in therapeutic failure of some but not all
      antibiotic regimens. In our region, skin carriage of resistant strains by 60% of
      acne patients and 1 in 2 of their close contacts suggests that resistant strains
      are widely disseminated. We are beginning to gain an understanding of those
      factors which encourage resistance development and can identify those patients
      most likely to possess resistant propionibacterial floras. Recommendations for
      the use of antibiotics in acne therapy to help prevent the emergence of
      resistance in P. acnes include the implementation of antibiotic usage policies
      and the encouragement of improved prescribing habits.

PMID- 9557229
TI  - Propionibacterium acnes and acne.

PMID- 9557230
TI  - Resistance to erythromycin and clindamycin in cutaneous propionibacteria is
      associated with mutations in 23S rRNA.

PMID- 9557231
TI  - The adhesion of cutaneous micro-organisms to human skin lipids.

PMID- 9557232
TI  - Construction of a lux reporter system for the analysis of the regulation of
      Staphylococcus epidermidis lipases.

PMID- 9557233
TI  - The pilosebaceous unit is part of the skin immune system.
AB  - It is well established that the functional state of sebaceous glands in vivo is a
      tightly regulated process orchestrated through the interaction of male sex
      hormones and functional androgen receptors expressed on sebocytes. In the last
      few years, however, it has become increasingly apparent that sebocytes like
      epidermal keratinocytes express a variety of cytokines which are implicated in
      inflammatory and immune responses. For example, sebocytes in vivo have been found
      to highly express tumor necrosis factor alpha (TNF-alpha) as determined by
      immunohistochemical and electron-microscopic methods. Moreover, certain
      neuropeptides including vascular intestinal peptide and proopiomelanocortin
      (POMC) peptides as well as their receptors have been localized within the
      pilosebaceous unit of murine and human skin. Since POMC peptides such as alpha
      melanocyte-stimulating hormone have recently been shown to exert important
      immunoregulatory effects by antagonizing the function of proinflammatory
      cytokines (e.g interleukin 1, interleukin 6 and TNF-alpha), induction of
      immunosuppressive cytokines (like interleukin 10), modulation of costimulatory
      molecule expression (e.g. B7-2) or suppression of macrophage-derived nitric
      oxide, complex interactions between these mediators and their target cells within
      the pilosebaceous gland seem to exist. The successful cultivation of sebocytes
      will provide a model by which the effect of these mediators can be studied in
      detail in order to shed light onto the various pathophysiological conditions of
      sebaceous glands.

PMID- 9557234
TI  - Inflammatory acne represents hypersensitivity to Propionibacterium acnes.
AB  - Hypersensitivity to P. acnes may account for the great variation in acne
      severity. Alternative explanations such as hyperandrogenism fail to account for
      disease severity in large numbers of patients.

PMID- 9557235
TI  - The possible role of reactive oxygen species generated by neutrophils in
      mediating acne inflammation.
AB  - The purpose of this study was to investigate the possible role of reactive oxygen
      species (ROS) generated by neutrophils in mediating acne inflammation.
      Antibiotics used for the treatment of acne significantly inhibited ROS generated
      by neutrophils, when compared to other antibiotics. Metronidazole, which is
      effective in the treatment of acne, markedly inhibited ROS generated by
      neutrophils. The drug is known to have no significant effect on the growth of
      Propionibacterium acnes. The proportion of linoleic acid is markedly decreased in
      acne comedones. Linoleic acid significantly suppressed ROS generated by
      neutrophils. The ability of neutrophils to produce ROS was significantly
      increased in patients with acne inflammation. These results seem to reveal the
      involvement of ROS generated by neutrophils in the disruption of the integrity of
      the follicular epithelium, which is responsible for inflammatory processes of
      acne.

PMID- 9557236
TI  - Inflammation in acne vulgaris: failure of skin micro-organisms to modulate
      keratinocyte interleukin 1 alpha production in vitro.

PMID- 9557237
TI  - Vascular endothelial growth factor expression induced by proinflammatory
      cytokines (interleukin 1 alpha, beta) in cells of the human pilosebaceous unit.

PMID- 9557238
TI  - Clinical aspects of acne.
AB  - Acne vulgaris may present in a wide variety of clinical forms depending on the
      type, number and severity of the predominant lesion. Thus there may be mild,
      moderate or severe comedonal or inflammatory acne, the latter with many subtypes.
      Furthermore, the number and extent of the lesions do not necessarily predict the
      response to therapy, and patients may also be categorized as therapeutically
      responsive or therapeutically refractory. Finally, there may be alterations in
      the clinical manifestations and therapeutic response depending on the
      distribution of the lesions, age of the patient and provoking or complicating
      factors.

PMID- 9557239
TI  - A review of infantile and pediatric acne.
AB  - Acne occurs primarily in the first year of life and at puberty. Neonatal and
      infantile acne may reflect the relatively high androgens from the adrenal in
      girls and the adrenal and testes in boys characteristic of this age. Early in
      puberty, acne in boys and girls is primarily comedonal and midfacial. The best
      predictors of severe acne are early onset of comedones and serum levels of
      dehydroepiandrosterone sulfate. Early recognition and therapy of acne may prevent
      scarring and psychological stress.

PMID- 9557240
TI  - Variation in pilosebaceous duct keratinocyte proliferation in acne patients.

PMID- 9557242
TI  - Acneiform dermatoses.
AB  - Acneiform dermatoses are follicular eruptions. The initial lesion is
      inflammatory, usually a papule or pustule. Comedones are later secondary lesions,
      a sequel to encapsulation and healing of the primary abscess. The earliest
      histological event is spongiosis, followed by a break in the follicular
      epithelium. The spilled follicular contents provokes a nonspecific lymphocytic
      and neutrophilic infiltrate. Acneiform eruptions are almost always drug induced.
      Important clues are sudden onset within days, widespread involvement, unusual
      locations (forearm, buttocks), occurrence beyond acne age, monomorphous lesions,
      sometimes signs of systemic drug toxicity with fever and malaise, clearing of
      inflammatory lesions after the drug is stopped, sometimes leaving secondary
      comedones. Other cutaneous eruptions that may superficially resemble acne
      vulgaris but that are not thought to be related to it etiologically are due to
      infection (e.g. gram-negative folliculitis) or unknown causes (e.g. acne
      necrotica or acne aestivalis).

PMID- 9557241
TI  - Continuous education for acne--basics, pathogenesis, differential diagnosis,
      clinic and therapy. Development of an interactive hypermedia application on CD
      ROM for computer-based learning and instruction.

PMID- 9557243
TI  - Coping with acne vulgaris. Evaluation of the chronic skin disorder questionnaire
      in patients with acne.
AB  - The present study investigated how patients with acne vulgaris cope with their
      disease. By means of questionnaires, relations and interactions between acne and
      psyche were evaluated. In addition to the evaluation of a specific questionnaire
      for patients with chronic skin disorders (CSD), assessing psychosocial impairment
      by the disease, depression and social anxiety were investigated in patients with
      acne. The study included 50 patients with acne. The CSD showed significant
      correlations with Beck's depression inventory, the interaction-anxiety
      questionnaire and the health locus of control scale. The CSD revealed significant
      differences compared to a control group of 33 patients with healthy skin.
      Furthermore the patients' attitudes towards triggering factors and disease
      related limitations in everyday life are presented. The results of the study
      demonstrate that patients with acne suffer from emotional distress and
      psychosocial problems caused by their disease; however, impairment is not
      correlated with the objective severity of acne.

PMID- 9557244
TI  - Psychotherapeutic approach in acne treatment.
AB  - From a medical psychological point of view, acne vulgaris can be schematically
      divided into two clinical pictures: (1) the common adolescent eruption, more mind
      influencing and thus somatopsychic; (2) the less frequent acne of adults (young
      adults for the most part), both as a continuation of adolescent acne and, more
      rarely, as a never before experienced cutaneous affection, and thus psychosomatic
      in a strict sense. We believe that the dermatologist can treat both of these
      clinical manifestations, even from a psychological aspect, from the very first
      visit with the patient using the first step in psychotherapy: counseling. The
      principal points of this approach are presented, with special attention to the
      differences to be considered in the two clinical pictures specified as well as to
      the opportuneness and timing of an eventual liaison consultation with
      psychologists/psychiatrists in realizing other therapeutic strategies.

PMID- 9557245
TI  - Topical drug treatment in acne.
AB  - The main part of acne treatment uses the topical route. More than 50% of acne
      patients belong to the group presenting with acne comedonica and papulopustulosa.
      Whenever small nodes or scarring occur, systemic comedication is indicated,
      however. Topical treatment affects at least three of the four main pathogenetic
      factors responsible for the development of acne, i.e. hyperseborrhea,
      hyperkeratosis, microbial colonization and inflammation. The agents currently
      available influence at least one of these factors but often have additional
      properties. Those which act in a comedolytic and anticomedogenic manner are the
      retinoids tretinoin, isotretinoin, adapalene and tazarotene and azelaic acid as
      well, some of the retinoids having additional anti-inflammatory potency. Azelaic
      acid has strong antibacterial potency without inducing bacterial resistance
      similar to benzoyl peroxide. Unfortunately, bacterial resistances are beginning
      to emerge as a significant problem. Propionibacterium acnes resistance to the
      commonly used erythromycin can also be transferred to clindamycin, whereas no
      resistance has been reported to nadifloxacin so far. Today, more and more
      evidence comes up that topical antiandrogenic agents will soon be available to
      treat the important factor seborrhea, because patients with marked hyperseborrhea
      frequently relapse. Finally, liposome encapsulation of agents including
      phospholipids can enhance penetration and efficacy but, particularly with regard
      to retinoids, can lead to higher absorption and adverse drug reactions.

PMID- 9557246
TI  - New insight into the topical management of excessive sebum flow at the skin
      surface.
AB  - The sebum flow dynamics at the skin surface results from a multistep process
      starting with sebocyte proliferation, intracellular lipid synthesis, cell lysis
      in the sebaceous duct, storage of sebum in the follicular reservoir, discharge
      through the follicular opening and spreading over the stratum corneum. A handful
      of topical products may decrease the sebum output, most of them acting at the
      level of the follicular reservoir function. Among them, elubiol exhibits a
      clinically relevant effect on oily skin.

PMID- 9557247
TI  - An overview of topical antibiotics for acne treatment.
AB  - Topical use of antibiotics is currently a widely accepted effective and safe
      treatment for acne. A review of the articles published in the past 30 years
      revealed that topical application of antibiotics such as erythromycin,
      clindamycin or tetracycline showed clinical effectiveness for mild to moderate
      inflammatory acne, especially when they are combined with zinc, tretinoin or
      benzoyl peroxide, while they showed little influence on noninflammatory acne. The
      main mechanism of action of topical antibiotics for acne treatment is inhibition
      of inflammation caused by bacteria rather than a direct bactericidal effect. The
      adverse reactions of topical antibiotics are mostly minor and negligible, while
      special attention should be given to the risk of development of resistant strains
      of Propionibacterium acnes. The development of new antibiotics is promising and
      will provide a wider range of therapeutic options for refractory cases.

PMID- 9557248
TI  - Systemic antibiotics for acne.
AB  - Antibiotic therapy for acne is very common. Antibiotics are frequently used in
      acne, either systemically or topically. Systemic antibiotics are indicated as
      treatment of moderate and quite severe acne or if acne is considered as very
      serious by the patient for psychological or social reasons. Results are very
      often excellent, but failure is possible; in this case using another treatment,
      especially isotretinoin, is necessary. A few antibiotics are useful:
      tetracyclines (tetracycline, doxycycline, minocycline, lymecycline),
      erythromycin, co-trimoxazole and trimethoprim. Their side effects are reviewed.
      During pregnancy the best antibiotic is erythromycin. For the nursing mother it
      is generally said that tetracyclines are contraindicated but the risks if they
      exist are certainly slight. The mechanism of action of systemic antibiotics for
      acne is not perfectly clear as it is not only antimicrobial: they diminish
      chemotaxis of polymorphonuclear leukocytes, modify the complement pathways and
      inhibit the polymorphonuclear leukocyte chemotactic factor and the lipase
      production in Propionibacterium acnes.

PMID- 9557249
TI  - Oral retinoids in the treatment of seborrhoea and acne.
AB  - Isotretinoin is an extremely effective drug if given systemically in severe forms
      of seborrhoea and acne, being the only retinoid with potent sebostatic
      properties. Its unique activity on the sebaceous gland still remains unclear
      since isotretinoin barely binds to cellular retinoic-acid-binding proteins and to
      retinoic acid receptors. Its bioavailability is approximately 25% and can be
      increased by food 1.5-2 times; after 30 min, the drug is detectable in the blood
      and maximal concentrations are reached 2-4 h after oral intake. The major
      metabolites of isotretinoin in blood are 4-hydroxy- and 4-oxo-isotretinoin, while
      several glucuronides are detectable in the bile. 4-Oxo-isotretinoin is present in
      plasma in a 2- to 4-fold higher concentration 6 h after a single dose. Steady
      state concentrations appear after 1 week. The half-life elimination rate of the
      parent compound ranges from 7 to 37 h while that of some metabolites does so from
      11 to 50 h. Isotretinoin crosses the placenta and is recognized as a strong
      teratogenic compound. About 10-30% of the drug is metabolized via its isomer
      tretinoin. Excretion of isotretinoin occurs after conjugation with the faeces or
      after metabolization with the urine. The epidermal levels of isotretinoin are
      rather low and no progressive accumulation, either in serum or in the skin, is
      found. After discontinuation of therapy, isotretinoin disappears from serum and
      skin within 2-4 weeks. Isotretinoin is the most effective drug in reducing
      sebaceous gland size (up to 90%) by decreasing proliferation of basal sebocytes,
      suppressing sebum production and inhibiting sebocyte differentiation in vivo. The
      molecular basis for its antisebotrophic activity has not been fully elucidated.
      Isotretinoin also exhibits anti-inflammatory activities. Systemic isotretinoin is
      today the regimen of choice in severe seborrhoea, since it reduces sebocyte lipid
      synthesis by 75% with daily doses as low as 0.1 mg/kg after 4 weeks. Patients who
      have received oral isotretinoin therapy for seborrhoea do not usually experience
      a relapse for months or years. In severe acne, a 6- to 12-month treatment with
      isotretinoin 1 mg/kg/day reduced to 0.5 or 0.2 mg/kg/day according to the
      response is recommended (cumulative dose of > 120 mg/kg). Contraception is
      essential during isotretinoin treatment in women of childbearing age 1 month
      before, during and for 3 months after discontinuation of treatment.

PMID- 9557250
TI  - Oral contraceptives and cyproterone acetate in female acne treatment.
AB  - The sebaceous gland is a target of androgens, and hormonal influences play an
      important role in the multifactorial pathogenesis of acne. In both men and women,
      acne may be related to an excessive hypersensitivity of the sebaceous end organ
      to androgens. However, in women, the ovarian and adrenal production and the
      plasma transport of androgens may be implicated, particularly in late-onset or
      persistent acne or with associated hirsutism. Many reports have shown that
      females with acne frequently have abnormal levels of circulating androgens.
      Hormonal treatment is not usually the first line in female acne. But in relation
      to the possibilities, particularly the tetracyclines, this may be a choice when
      one prescribes a pill like Dianette to a young woman presenting a mild acne and
      who requests contraception. However, antiandrogen treatment is sometimes
      mandatory, especially in resistant acne in adult women and/or in female acne
      which is resistant or relapsing rapidly after treatment with Roaccutane and which
      is often related to hyperandrogenism. Finally, in severe prepubertal acne, the
      possible cause is an adrenal enzymatic block of which the only treatment is
      hormonal.

PMID- 9557251
TI  - Other antiandrogens.
AB  - Various substances of steroidal or nonsteroidal structure may serve as an
      alternative for the antiandrogenic treatment of acne. Compounds with
      antiandrogenic properties like cimetidine or ketoconazole are rarely administered
      for acne due to their weak effects. In contrast, spironolactone is an effective
      antiandrogen that shows good treatment effects in hirsutism and acne. Side
      effects occur frequently and are dose dependent. Isotretinoin--the most effective
      agent in acne therapy--has been under discussion for additional antiandrogenic
      properties for years. At present there is additional evidence for the
      antiandrogenic effects of isotretinoin. Regarding substances acting on both
      levels, androgen receptor binding and 5 alpha-reductase inhibition, the question
      is raised whether the term 'antiandrogen' should be amplified by including the 5
      alpha-reductase inhibitors. This would pay tribute to the biological aspect of
      antiandrogenicity that takes into account not only the mode of action but also
      the effects of the substance. Under this aspect type 1 5 alpha-reductase
      inhibitors may gain attention in the future.

PMID- 9557252
TI  - Why and when the treatment of acne fails. What to do.
AB  - The majority of acne patients show a good response to the proper acne treatment.
      However, a small percentage not exceeding 10-15% do not respond as satisfactorily
      as expected. The main reason for the treatment failure is the poor patient
      compliance. In order to improve the patient compliance the strategy for the
      treatment of acne has to be carefully planned and includes the following:
      discussion before treatment; give clear instructions; explain the rhythm of
      improvement; explain the role of cosmetics; explain the role of sunbathing;
      explain the expected side effects. It has to be emphasized that all acne cases
      can be adequately controlled if the relationship between doctor and patient has
      been built on trust and confidence, maximizing the patient compliance.

PMID- 9557253
TI  - Comedonal diffusion of minocycline in acne.

PMID- 9557254
TI  - Oral isotretinoin in HIV-positive women with acne: report of three cases.

PMID- 9557255
TI  - A new concept of drug delivery for acne.
AB  - Adapalene is a stable naphthoic acid derivative that displays a strong retinoid
      agonist pharmacology. This drug controls cell proliferation and differentiation,
      and possesses significant anti-inflammatory action. The retinoid action of
      adapalene are mediated by the ligand-activated gene transcription factors
      retinoic acid receptors RAR beta and RAR gamma. We describe here how an aqueous
      gel containing adapalene was selected for the topical treatment of acne.

PMID- 9557256
TI  - Polymorphisms in the human cytochrome P-450 1A1 gene (CYP1A1) as a factor for
      developing acne.
AB  - Cytochromes P-450 are a supergene family of enzymes involved in the metabolism of
      a wide range of endogenous and foreign compounds. The existing genetic variations
      of the distinct isozymes lead to interindividually different metabolic capacity.
      Since vitamin A, endogenous retinoids and their natural metabolites are
      morphogenic for the sebaceous gland, we investigated the polymorphisms of
      cytochrome P-450 1A1, as being one of the most active isozymes involved in their
      interconversion. From the known mutations, two were investigated; an additional
      cleavage site for MspI in the 3'-flanking region identified as a thymine-to
      cytosine transition 1,194 bp downstream of exon 7 (m1) and an adenine-to-guanine
      transition at position 4889 in exon 7 (m2). We studied 96 acne patients for m1
      and m2 mutations by restriction fragment length polymorphism and allele-specific
      polymerase chain reaction, respectively, and compared the results with 408
      reference individuals. No statistically significant difference was found in the
      distribution of m2 alleles; the frequency was 3.13 and 3.06% of the alleles,
      respectively (odds ratio = 1.02, confidence limits 0.41-2.52, p = 0.96). In
      contrast, a trend to an overrepresentation of m1 alleles in acne patients was
      observed; allele frequency was 8.33 in the patients and 6.99% in the control
      subjects, respectively (odds ratio 1.21, 95% confidence limits 0.68-2.16, p =
      0.52). As the m1 mutation might define a marker for alterations on regulatory
      sites, the biological efficacy of natural retinoids could be greatly impaired by
      their rapid metabolism to inactive compounds. The resulting deficit of active
      natural retinoids may lead to abnormal sebocyte differentiation and
      hyperkeratinization of the follicular canal implicating the development of acne
      in some patients.

PMID- 9557257
TI  - Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin
      and 4-oxo-isotretinoin. A useful tool for management of severe acne.
AB  - BACKGROUND: Isotretinoin for oral therapy in severe acne conglobata and acne
      nodulocystica represents a significant achievement; however, the drug exerts
      several mucocutaneous and systemic adverse effects, besides its teratogenic
      potency. OBJECTIVE: The aim of this study was to investigate the plasma levels of
      isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne
      and to assess any correlation with the given dose, the clinical improvement and
      the occurrence of side effects. METHODS: Forty-one patients with severe acne and
      acne-related disorders were studied under long-term oral intake of isotretinoin.
      Therapeutic effects and side effects were evaluated prior, during and at the end
      of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxo
      isotretinoin were measured by reversed-phase HPLC and were correlated with the
      administered oral dose and the number and frequency of side effects. RESULTS:
      Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At
      a mean dosage of 0.75-1.0 mg/kg/day, 404 +/- 142 ng/ml were measured, whereas the
      plasma levels of 4-oxo-isotretinoin were 1-2x higher. The plasma levels
      correlated well with the orally administered dose of isotretinoin and the
      observed mucocutaneous side effects. CONCLUSION: The study demonstrates that
      measuring of the plasma levels may be a helpful tool to monitor the individual
      therapeutic dose regimen in patients with severe acne in order to minimize
      undesired side effects and to control oral intake.

PMID- 9557258
TI  - Fine-needle aspiration of Merkel cell carcinoma of the skin with cytomorphology
      and immunocytochemical correlation.
AB  - Merkel cell carcinoma (MCC) of the skin is a rare, primary malignant skin
      neoplasm which can present as a cutaneous nodule. These neoplasms are seen
      primarily in the elderly and located in the head and neck area or extremities.
      Twenty-nine aspirates from primary and metastatic lesions obtained by
      percutaneous fine-needle aspiration in 19 patients have been studied. The
      cytomorphologic features, clinical information, and immunocytochemical (ICC)
      findings are detailed. Aspirate smears demonstrated small-to-intermediate-sized
      cells with a loosely cohesive pattern. Nuclei were round with finely granular
      chromatin and multiple, small nucleoli. Cells possessed a thin rim of cytoplasm,
      and infrequent pseudorosette formations were noted in cell groups. ICC results
      were universally positive for cytokeratin, which showed a paranuclear "dot-like"
      pattern. Neuron-specific enolase, epithelial membrane antigen, and S-100 protein
      were positive in varying degrees. Leukocyte common antigen was universally
      negative. The diagnosis of MCC of the skin by FNA can be made by applying
      cytologic features in addition to ancillary studies and clinical information.

PMID- 9557259
TI  - Ultrasound-guided fine-needle aspiration cytology diagnosis of gallbladder
      lesions: a study of 82 cases.
AB  - Carcinoma of the gallbladder (GB) is among the five most common forms of cancers
      and tops the list of gastrointestinal malignancies in females of the Delhi
      region. Lack of specific signs and symptoms prevents early detection of GB
      carcinoma. However, in recent years ultrasonographically (US)-guided fine-needle
      aspiration (FNA) cytology has been found to be a reliable procedure for its
      diagnosis. The present study was carried out during a period of 5 yr (1986-1990)
      in 64 female and 18 male patients to find out the diagnostic utility of US-guided
      FNA cytology in gallbladder lesions. Ultrasonography in these 82 cases revealed a
      mass in the gallbladder/GB area in 74 (90.2%), a mass in the GB/pancreas in 1
      (1.2%), gallstones in 32 (39.0%), and miscellaneous gallbladder lesions in 4
      (4.9%). The other findings included space-occupying lesions in liver in 18
      (22.0%), portal lymphadenopathy in 12 (14.6%), and infiltration in other organs
      in 7 (8.5%). The initial cytodiagnosis was malignancy in 48 cases, inflammatory
      in 12, and inadequate in 22. Following review of the smears by one of the
      investigators (D.K.D.), the number of malignant cases remained 48 (58.5%). There
      were 10 (12.2%) inflammatory and 24 (29.3%) inadequate cases. Adenocarcinoma was
      the most common malignancy (83.3%), followed by squamous-cell and adenosquamous
      carcinoma (12.5%) and small round cell tumors (4.2%). The 10 inflammatory lesions
      showed slight (+) to excessive (+3) neutrophilic infiltration and included one
      case each of xanthogranulomatous cholecystitis and a necrotizing granulomatous
      lesion likely to be of tuberculous etiology.

PMID- 9557260
TI  - Optimization of the peritoneal lavage.
AB  - Review of 275 consecutive peritoneal lavages and concurrent histologic material
      from gynecologic operations suggested that cytologic evaluation was clinically
      indicated for only 60.7% of the lavages, representing 46% of the patients in the
      study. More than one concurrent lavage was received from 21.6% of all patients in
      the study, comprising 50% of patients with malignant lavages, 18.7% of patients
      with benign lavages, and 5.3% of patients for whom cytologic evaluation of
      peritoneal lavage was not clinically indicated. Malignant cells were diagnosed in
      15% of the 167 lavages for which cytologic examination was clinically indicated.
      In this series of patients, identification of malignant cells in peritoneal
      lavages did not increase the tumor stage beyond that obtained solely from
      examination of the concurrent histologic material. There were no false-positive
      cytologic diagnoses and no lavages in which neoplastic cells were misinterpreted
      as benign. A significant number of lavages, including several from patients with
      histologically confirmed peritoneal tumor, were sparsely cellular and/or
      excessively bloody. It is suggested that although peritoneal lavages might be
      collected during all gynecologic operations, only specimens from selected cases
      should be submitted for cytologic evaluation, and greater attention should be
      given to specimen collection to ensure that only well-preserved and
      representative material from the peritoneum is submitted for cytologic
      evaluation.

PMID- 9557261
TI  - Fine-needle aspiration cytology of amyloid associated with nonneoplastic and
      malignant lesions.
AB  - To assess the value of fine-needle aspiration (FNA) cytology for the diagnosis of
      amyloid, we retrospectively studied all FNA cases diagnosed as having amyloid
      during a 6-yr period (1990-1996). FNA was performed on both superficial and deep
      locations. A total of 6 cases containing amyloid was studied, including primary
      medullary thyroid carcinoma, metastatic medullary thyroid carcinoma to a
      vertebrae, multiple myeloma, squamous-cell carcinoma of the lung metastatic to a
      hilar lymph node, primary pulmonary amyloid, and amyloid tumor in a vertebral
      body in a patient with primary systemic amyloidosis. Despite the location or
      disease association, the cytologic appearance of amyloid in all cases was
      similar. On Diff-Quik stain, amyloid appeared as amorphous, irregular, waxy
      basophilic to metachromatic clumps of material. Papanicolaou stain revealed
      cyanophilic to organophilic clumps of material with occasional prominent
      fissures. In all 6 cases, amyloid was confirmed by Congo red stain and in 3 cases
      by a thioflavin T stain. In 4 of the 6 cases (67%), amyloid was associated with
      an underlying malignancy. In 3 cases malignant cells were admixed with the
      amyloid, and in another case malignancy was present at a distant site. We
      conclude that FNA biopsy is a helpful initial procedure for the evaluation of
      patients with amyloid deposits. The clinical implications of amyloid found in any
      particular body site include both benign and malignant conditions. The presence
      of an associated neoplasm must be especially considered in the differential
      diagnosis of amyloid deposits.

PMID- 9557262
TI  - Renal medullary carcinoma: report of a case with positive urinary cytology.
AB  - Renal medullary carcinoma is an aggressive neoplasm of the renal pelvis arising
      in patients with a history of sickle-cell trait. The authors report a case of
      renal medullary carcinoma with positive urinary cytology. Due to the location of
      the tumor in the renal pelvis and the loosely cohesive nature of poorly
      differentiated neoplasms, the presence of renal medullary carcinoma in a urinary
      cytology specimen is not surprising. The cytologic characteristics as well as the
      ultrastructural features are described.

PMID- 9557263
TI  - Metastatic pulmonary leiomyosarcoma: cytopathologic diagnosis on sputum
      examination.
AB  - Pulmonary metastasis of sarcomas is not uncommon. Rarely, endobronchial
      involvement may result in exfoliation of diagnostic cells in sputum. This case
      report is of a 71-yr-old man with a history of lower leg leiomyosarcoma who
      developed multiple lung metastases. Sputum examination revealed malignant cells
      with pleomorphic, elongated, and cigar-shaped nuclei and occasional bipolar
      cytoplasmic processes. Immunoperoxidase studies on the smears using desmin and
      smooth muscle actin were strongly positive, consistent with leiomyosarcoma.
      Confirmation of metastatic lung disease by sputum cytology not only has
      prognostic importance but also obviates the need for further investigations.

PMID- 9557264
TI  - Malignant melanotic schwannoma fine-needle aspiration biopsy findings.
AB  - We describe the cytologic, histologic, and clinical features of two cases of
      melanotic schwannoma, arising in the neck and superior mediastinum, respectively.
      Cytologic findings in both cases included the presence of cells with heavily
      pigmented cytoplasm, showing long branching projections. The cells were arranged
      in clusters, with ill-defined boundaries. Histologic findings included
      interlacing fascicles of cells, with abundant melanin pigment, calcification, and
      necrosis. Immunohistochemical stains were positive for S. 100 protein and anti
      human melanoma (HMB45). Both patients died with metastases.

PMID- 9557265
TI  - Fine-needle aspiration cytology of malignant retroperitoneal paraganglioma.
AB  - The cytologic findings in a fine-needle aspiration sample are described from a
      large retroperitoneal mass in a 56-yr-old male. The aspiration was performed
      under CT guidance using a 22-gauge needle, maintaining negative pressure. For
      cytologic study, on-site smears were prepared and stained by the Papanicolaou
      method. Additionally, cytospin, filter preparations, cell blocks from the
      aspirate, histology, and electron microscopy of the tumor tissue were performed.
      Also, immunodiagnostic staining for neuron-specific enolase (NSE), chromogranin,
      S-100 protein, vimentin, HMB45, cytokeratin, and Grimelius preparation was
      performed on cytologic and histologic material. The cytologic material was
      characterized by cords, suggestive acinar structures, and small follicle-like
      clusters of cells, while cell blocks from the aspirate showed oval or spindle
      shaped nuclei with a somewhat fasciculated appearance. However, sections from the
      tumor tissue showed an organoid "zellballen" pattern. The nuclei were round,
      oval, spindly, and epithelioid, with moderate to scanty cytoplasm, smooth nuclear
      membranes, fine, evenly dispersed chromatin, slight hyperchromasia, and mild
      pleomorphism. No intranuclear vacuoles were seen. Positive immunohistochemical
      staining for NSE, chromogranin, and Grimelius preparation was noted in the tumor
      cells, while staining for vimentin, HMB45, and cytokeratin was negative. Electron
      microscopy of the tumor tissue revealed the presence of variable numbers of
      round, membrane-bound, electron-dense neurosecretory granules. The cytohistologic
      and ultrastructural findings are presented, as well as the results of
      immunodiagnostic staining which helped in the diagnosis of retroperitoneal
      paraganglioma, an infrequently reported tumor.

PMID- 9557267
TI  - Fine-needle aspiration cytology of renal angiomyolipoma: report of a case with
      immunocytochemical and electron microscopic findings.
AB  - A case is presented in which the diagnosis of renal angiomyolipoma was made by
      computed tomography (CT)-guided, fine-needle aspiration cytology and the
      examination of a cell block. The tumor was characterized by epithelioid smooth
      muscle cells, blood vessels and fat in the cytologic material. The cytodiagnosis
      was further substantiated by positive staining of the epithelioid muscle cells
      for markers of muscle-specific actin, HMB45, and trace positivity for vimentin
      but not with S100 protein, desmin, or cytokeratin. Further studies for the
      recently described crystalloids were also performed by using the periodic-acid
      Schiff stain with and without diastase treatment and electron microscopy on the
      cytologic material. However, no such crystalloids were found. A preoperative
      cytologic diagnosis of renal angiomyolipoma was considered to be of value due to
      the difference in management between angiomyolipoma and a renal carcinoma, both
      of which can present as a renal mass on imaging.

PMID- 9557266
TI  - Metastatic papillary oncocytic carcinoma of the pancreas to the liver diagnosed
      by fine-needle aspiration.
AB  - A 37-year-old white male with a large pancreatic mass was referred to our
      institution with a hypodense liver lesion detected on CT scan. A fine-needle
      aspiration (FNA) was performed on the liver lesion. Diff-Quik smears demonstrated
      scattered papillary structures and single neoplastic cells with abundant well
      defined dense granular cytoplasm. Eccentrically located nuclei were noted with
      single prominent nucleoli. Cell block preparations showed papillary structures
      lined by cells with abundant pink granular cytoplasm, hyperchromatic nuclei, and
      prominent single nucleoli. Electron microscopic examination displayed numerous
      but poorly preserved mitochondria. The diagnosis of papillary carcinoma with
      oncocytic features was made. Only two previous cases of pancreatic oncocytic
      tumors diagnosed by FNA have been reported in the literature. We present an
      additional case, notable in that the diagnosis was made in a metastatic liver
      nodule.

PMID- 9557268
TI  - Bronchioloalveolar carcinoma: diagnostic pitfalls and immunocytochemical
      contribution.
AB  - Because bronchioloalveolar carcinoma (BAC) commonly displays bland cytologic
      appearance, there is a good potential for misinterpretation. The aim of this
      study was twofold: one was to identify the most reproducible cytomorphologic
      features to distinguish BAC from conventional lung adenocarcinoma (CLA) on fine
      needle aspiration (FNA), and the other was to investigate the staining
      characteristics of these two variants of lung carcinoma with P53 tumor suppressor
      gene immunostain and their potential value in the distinction between the two
      entities. Cytology records of 13 histologically documented BACs was retrieved: 7
      FNA, 3 bronchial washing/bronchial brushing (BW/ BB), and 3 scraping smears of
      surgical specimens. Two cases had both FNA and BW/BB material. Immunostains for
      P53 protein, carcinoembryonic antigen (CEA), and Ki67(MIB-1) monoclonal
      antibodies were performed on 13 BACs (FNA cell blocks and tissue) and on 11 FNA
      cell blocks of CLA. Cytologically, BAC showed uniform cells with abundant, lacy
      cytoplasm, and bland, folded nuclei arranged singly, in papillary clusters, and
      sheets. Immunocytochemically, one BAC and one CLA were technically unacceptable.
      Of the 12 remaining BAC cases, 10 were reactive with CEA, 9 reactive with Ki67 (>
      5%), and 4 reactive with P53. Of the 10 remaining CLAs, 9 were positive with CEA,
      9 were reactive with Ki67 (> 5%), and 8 were reactive with P53. We conclude that
      BAC demonstrates distinctive cytologic features, but difficulty may be
      encountered with well-differentiated CLA, metastatic adenocarcinoma, and other
      lesions. Immunocytochemically, CEA and Ki67 do not appear to be discriminate, but
      P53 may be of value in distinguishing BAC from CLA. Attention to subtle nuclear
      changes, characteristic grouping, cellular arrangement, and P53 reactivity could
      enable cytopathologists to accurately diagnose BAC.

PMID- 9557270
TI  - Is the cytologic diagnosis of esophageal glandular dysplasia feasible?
AB  - Barrett's esophagus is a premalignant condition in which the normal stratified
      squamous epithelium of the esophagus is replaced by metaplastic glandular
      epithelium. Patients with Barrett's esophagus are at increased risk for the
      development of esophageal adenocarcinoma. Because dysplasia precedes the
      development of frank adenocarcinoma, the cytologic detection of esophageal
      glandular dysplasia represents a potentially inexpensive and efficient means of
      monitoring disease progression to adenocarcinoma and identifying high-risk
      patients. This article discusses the current status of exfoliative cytology as a
      screening test for glandular dysplasia of the esophagus.

PMID- 9557269
TI  - PAPNET computer-aided rescreening for detection of benign and malignant glandular
      elements in cervicovaginal smears: a review of 61 cases.
AB  - An increasing proportion of the recent cytodiagnostic literature has focused on
      automation of the Pap smear screening process in hopes of finding a feasible
      system to aid in the reduction of the number of reported false-negative cases. In
      a sense, these systems can be thought of as computer-driven sensitivity enhancers
      for better detection of abnormalities in smeared cervicovaginal specimens. The
      PAPNET system (Neuromedical Systems, Inc., Suffern, NY) relies on a neural
      network of artificial-intelligence technology to recognize the complex cellular
      arrays present in Pap smears, and was originally intended to aid in the
      identification of morphologically abnormal cells of squamous origin. Herein, we
      present the results of 61 smears containing a mixture of known diagnostically
      important benign, dysplastic, and malignant glandular cellular abnormalities
      which were reviewed by the PAPNET technology. The PAPNET system detected the
      diagnostic glandular material in 44 of the 45 benign cases reviewed (98%
      detection rate). In addition, the PAPNET technology identified abnormal cellular
      material in 15 of the 16 studied smears from patients with malignant/dysplastic
      morphology (94% detection rate). These data indicate that the PAPNET neural
      networks are capable of detecting cells with aberrant glandular cytomorphology.
      In both cases missed by the PAPNET system, the number of abnormal cells per slide
      was very low, indicating that as with human screeners, the capabilities of this
      semiautomated method may be exceeded when an extreme paucity of diagnostic
      cellular material is present in a given slide. Further and larger reviews of
      glandular abnormalities by automated technologies are needed to assess these
      systems for their true efficacy at diminishing false-negative cases.

PMID- 9557271
TI  - Cytohistologic discrepancies in cervical intraepithelial neoplasia and value of
      repeat cervical smears taken during colposcopy.

PMID- 9557272
TI  - [Antimicrobial activities of cefcapene against clinical isolates from respiratory
      tract infections of outpatients].
AB  - In order to evaluate antimicrobial activity of cefcapene (CFPN), minimum
      inhibitory concentrations (MICs) of CFPN and reference drugs were determined
      against clinical isolates from respiratory tract infection of out patients that
      were obtained in our laboratory from January to June of 1997. The results are
      summarized as follows; 1. The MIC90 of CFPN against penicillin (PC)-susceptible
      Streptococcus pneumoniae (PSSP) was equal to those of benzylpenicillin (PCG),
      ampicillin (ABPC) and cefditoren (CDTR), and was lower than those of cefaclor
      (CCL), cefdinir (CFDN) and erythromycin (EM). 2. The MIC90 of CFPN against PC
      intermediate S. pneumoniae (PISP)/PC-resistant S. pneumoniae (PRSP) was equal to
      that of CDTR, and was lower than those of PCG, ABPC, CCL, CFDN and EM. CFPN
      showing strong antimicrobial activities against PISP. 3. CFPN showed strong
      antimicrobial activities against beta-lactamase producing and non-producing
      Haemophilus influenzae. The MIC90 of CFPN was stronger than those of ABPC, CCL,
      CFDN and EM, and was approximately equal to that of CDTR. CFPN also showed strong
      antimicrobial activities against strains which did not produce any beta-lactamase
      and were resistant to CCL with MIC of > or = 25 micrograms/ml. 4. Antimicrobial
      activities of CFPN against Moraxella subgenus Branhamella catarrhalis was
      stronger than that of ABPC and CCL, though the MIC90 of CFPN was rather high,
      3.13 micrograms/ml. 5. CFPN showed strong antimicrobial activities against PISP
      and beta-lactamase producing H. influenzae, and also against the CCL-resistant H.
      influenzae indicative mutations of penicillin-binding proteins (PBPs). From those
      results, cefcapen-pivoxil was found to be clinically effective against community
      acquired respiratory tract infection.

PMID- 9557273
TI  - [In vitro antibacterial activities of cefteram and other beta-lactam agents
      against recent clinical isolates].
AB  - In vitro antibacterial activity of the third-generation oral cephem cefteram
      (CFTM)--ten years after its first use in the clinical setting--against recent
      clinical isolates was evaluated and compared with those of other oral cephems. A
      total of 851 clinical isolates belonging to 13 species used in this study were
      collected from five medical institutions across Japan during 1996. CFTM showed
      excellent antibacterial activity against methicillin-susceptible S. aureus and S.
      pyogenes, equivalent to those of other third-generation oral cephems, except
      cefixime. Of the S. pneumoniae strains, a high proportion, 34.1%, were penicillin
      resistant strains (PRSP), with MIC values of 2.0 micrograms/ml or above, but the
      MIC50 of CFTM against PRSP was 1.0 microgram/ml. CFTM and the other third
      generation oral cephems showed potent antibacterial activity against E. coli, K.
      pneumoniae, and P. mirabilis. A few strains of E. coli, however, were highly
      resistant to third-generation oral cephems; that might include extended-spectrum
      beta-lactamase producing strains. MIC values against P. vulgaris varied
      significantly, depending on whether they were determined by the broth micro
      dilution method or the agar dilution method; growth was observed at high
      concentrations in the broth micro-dilution method, in which the skip phenomenon
      was demonstrated, but not in the agar dilution method. The reason for this
      discrepancy is unknown. Most strains of S. marcescens, C. freundii, and E.
      cloacae demonstrated resistance to CFTM and the other third-generation oral
      cephems. CFTM and the other third-generation oral cephems showed excellent
      antibacterial activities against M. (B.) catarrhalis, N. gonorrhoeae, and H.
      influenzae, including ampicillin-resistant strains.

PMID- 9557275
TI  - [Change of cytokines and clinical efficacy of panipenem/betamipron in obstetric
      and gynecological infections. Yamagata Study Group of Panipenem/Betamipron in
      Obstetric and Gynecological Infections].
AB  - Efficacy and safety of panipenem/betamipron (PAPM/BP) in treatment of obstetric
      and gynecological infections, and change of interleukin-6 (IL-6) and interleukin
      8 (IL-8) levels in blood, as markers of infection, were investigated. The results
      were as follows; 1) Clinical efficacy of PAPM/BP by drip infusion of 1-2 g/day
      for 3-14 days against 52 patients with intrauterine infection (n = 29),
      pelveoperitonitis (n = 19), and other infections were 14 "Excellent" in 14 cases,
      "Good" in 35 cases, and efficacy rate was 94.2% (49/52). Both efficacy rate analy
      by causative organisms and eradication rate were 35/37 (94.6%). No subjective or
      objective side effects and no abnormal labolatory findings were observed. 2)
      Changes of IL-6 (> 4 pg/ml) levels in serum, as an infection marker, were
      observed in 8 cases out of 14 cases (57.1%), and correlation between CRP and IL-6
      in the treatment process was noticed. However, changes of serum IL-8 (> 12.5
      pg/ml) were observed in only 2 cases of those 14 cases (14.3%), indicative that
      IL-8 has no significance as a marker of infection.

PMID- 9557274
TI  - [The antimicrobial susceptibilities and serotypes of Pseudomonas aeruginosa
      isolated from sputum].
AB  - During the period of January 1992 and August 1995, 75 strains of Pseudomonas
      aeruginosa were isolated from sputum at the Hiroshima Prefectural Hiroshima
      Hospital. The antimicrobial susceptibilities and serotypes of those strains were
      investigated. The results are summarized as follows: 1. The analyses of
      antimicrobial susceptibilities revealed that meropenem (MEPM) was the most active
      among the carbapenems tested against those P. aeruginosa strains with MIC of < or
      = 6.25 micrograms/ml. All of the strains were thus found to be susceptible to
      MEPM, while 9 strains out of 75 (12%) were resistant to imipenem showing cross
      resistance to biapenem. 2. The activities of the beta-lactams other than
      carbapenems were found to be the order of cefozopran > or = ceftazidime >
      aztreonam > piperacillin with MIC50 and MIC90 ranging of 3.13-6.25 micrograms/ml
      and 25- > or = 100 micrograms/ml, respectively. 3. Among aminoglycosides tested,
      3 strains (4.0%) of the strains showed resistance to amikacin, however none of
      them were resistant to tobramycin. 4. Distribution of serotypes among the strains
      was; type G 22.7%, type M 21.3%, type A 16.0%, type B 13.3% and type E 8.0%.
      Strains of types M and E showed multiple resistance to beta-lactams except
      carbapenems. As documented in this study, the frequency of isolation of beta
      lactam-resistant P. aeruginosa (including carbapenem-resistant) is steadily
      increasing. Continuous surveillance of antimicrobial susceptibility among
      clinically isolated P. aeruginosa seems to be necessary.

PMID- 9557276
TI  - [Significance of coronary risk factors and coronary arteriosclerosis for coronary
      vasospasm].
AB  - The clinical significance of coronary arteriosclerosis and coronary risk factors
      was investigated in patients with coronary spasm. Coronary spasm induction test
      with acetylcholine was performed in 140 consecutive patients (85 males and 55
      females) with chest pain in our hospital. The patients were divided into
      positive, borderline, and negative groups according to the results of the test.
      The positive and borderline groups were categorized as the coronary contractive
      group. The coronary sclerosis index was used to evaluate the degree of coronary
      arteriosclerosis. Coronary risk factors were evaluated in terms of hypertension,
      diabetes mellitus, hyperlipidemia, obesity, history of smoking and drinking, and
      family history of cardiovascular events. Patients could be divided into 34.3% in
      the positive group and 23.6% in the borderline group, i.e. 57.9% in the coronary
      contractive group, and 42.1% in the negative group. There were more males than
      females in both positive and coronary contractive groups. The proportion of males
      in the coronary contractive group was higher in patients over 60 years of age
      than in patients under 60. In contrast, the proportion of females was higher in
      patients under 60 than in patients over 60. In male patients, the coronary
      sclerosis indices in the positive, borderline, and coronary contractive groups
      were higher than those in the negative group. The indices in female patients in
      the positive and coronary contractive groups were higher than the index in the
      negative group. There were no differences in terms of the presence or absence, or
      the degree of organic stenosis between spastic sites and nonspastic branches in
      the positive group. The history of smoking in male patients was significantly
      more common in the positive group than in the negative group. The family history
      was more relevant in female patients in the positive or coronary contractive
      group compared to the negative group. Moreover, the history of smoking in the
      coronary contractive group was significantly more common than that in the
      negative group. The development of coronary spasm may be determined, at least in
      part, by the degree of coronary sclerosis as well as by gender and age. Smoking
      habits in both sexes and family history in females are proposed as the most
      important risk factors for coronary spasm.

PMID- 9557277
TI  - [Usefulness of intracoronary injection of acetylcholine and ergonovine in
      patients with variant angina].
AB  - The correlation was examined between the angina-producing arteries predicted to
      be responsible for the sites of ST segment elevation during spontaneous ischemic
      attacks and the arteries in which spasm was induced by intracoronary injection of
      either acetylcholine or ergonovine in patients with variant angina. From 1991
      January to 1996 June, 42 patients with variant angina, 40 men and 2 women with a
      mean age of 61.6 years old, underwent the acetylcholine provocation test within 2
      weeks of observation of the last ST segment elevation. After discontinuation of
      antianginal agents for at least 24 hours, a bolus of acetylcholine was injected
      in incremental doses of 20, 50 micrograms (occasionally 80 micrograms) into the
      right coronary artery and of 20, 50 and 100 micrograms incrementally into the
      left coronary artery to provoke coronary spasm. Intracoronary injection of
      ergonovine was added in nine patients, in whom intracoronary injection of
      acetylcholine failed to document coronary spasm on the arteries predicted to be
      responsible for the sites of ST segment elevation during anginal attacks.
      Ergonovine was injected in total doses of 40 micrograms into the right coronary
      artery and of 64 micrograms into the left coronary artery. Positive spasm was
      defined as induction of more than 99% reversible stenosis. The correlation
      between the arteries predicted to be responsible for the sites of ST segment
      elevation during attacks and the vessels in which spasm was induced by
      acetylcholine test was 78.6% for all patients and 80.0% for all sites of ST
      segment elevation. By adding the ergonovine test after the acetylcholine test,
      the correlation increased to 95.2% for all patients and 95.6% for all sites of ST
      segment elevation. The correlation observed agrees with previous studies in which
      the ergonovine test was performed in patients without induced spasm by
      intracoronary injection of acetylcholine and that the super-imposed ergonovine
      test is useful for diagnosing patients with variant angina.

PMID- 9557278
TI  - [Effects of antihypertensive treatment on the thickening of the basal portion of
      the interventricular septum in essential hypertension].
AB  - Previous echocardiographic studies have indicated that the basal portion of
      interventricular septum is locally thickened in many patients with essential
      hypertension. This retrospective study investigated whether this localized
      thickening is decreased by antihypertensive treatment. Twenty-four patients with
      mild essential hypertension (15 males, 9 females, mean [+/- SD] 55 +/- 9 years)
      were selected who had local thickening at the basal portion of interventricular
      septum (> or = 11 mm) on echocardiograms recorded within 3 months after the first
      visit and were followed up by echocardiography 6 months or more after the start
      of antihypertensive treatment. Interventricular septal wall thickness at the mid
      portion (IVST), posterior wall thickness (PWT), left ventricular mass index
      (LVMI), aorto-septal angle, blood flow velocity in left ventricular outflow
      tract, and the thickness of the basal portion of interventricular septum (septal
      wall maximum thickness within 1.5 cm apex side from the joint of interventricular
      septum and aorta in the long-axis view of B-mode echocardiograms) were measured.
      Blood pressure was significantly decreased from 152.7 +/- 8.7/93.1 +/- 8.0 mmHg
      to 140.0 +/- 8.2/86.6 +/- 8.2 mmHg by treatment (p < 0.0001). The thickness of
      the basal interventricular septum was significantly reduced by treatment from
      12.3 +/- 1.7 mm to 10.3 +/- 1.4 mm (p < 0.0001). Mean IVST, PWT and LVMI were
      slightly reduced by treatment, but the differences were not statistically
      significant. These results suggest that the thickening of basal interventricular
      septum is induced by high blood pressure, and the measurement of the thickness of
      basal interventricular septum might be a useful tool to estimate and monitor the
      effect of antihypertensive treatment in patients with mild essential
      hypertension.

PMID- 9557279
TI  - [Serial changes in mitral regurgitation after mitral valve repair with artificial
      chordae tendineae: assessment by transesophageal echocardiography].
AB  - Serial changes in mitral regurgitation after anterior mitral valve repair were
      examined by transesophageal echocardiography (TEE) in 34 of 86 consecutive
      patients with pure mitral regurgitation who underwent anterior mitral valve
      repair from 1987 to 1996. The patients were divided into two groups: 15 patients
      undergoing mitral repair with polytetrafluoroethylene (PTFE; PTFE group) and 19
      undergoing conventional mitral repair without PTFE (non-PTFE group). The PTFE
      group included 11 men and 4 women with a mean age of 52.1 years. They were
      followed for mean 22.8 +/- 12.0 months. The non-PTFE group included 12 men and 7
      women with a mean age of 53.9 years. They were followed for mean 33.9 +/- 20.4
      months. Mitral regurgitation jet areas were observed at the time of operation, 1
      month after mitral valve repair, and in the late follow-up period. Regurgitation
      jet areas were 0.7 +/- 0.7, 1.1 +/- 0.9 and 2.5 +/- 2.1 cm2 in the PTFE group,
      and 1.1 +/- 1.3, 2.4 +/- 1.7, 4.7 +/- 2.9 cm2 in the non-PTFE group. The jet area
      was significantly smaller in the PTFE group than in the non-PTFE group at 1 month
      after operation and in the late follow-up period. Moderate to severe
      regurgitation was observed in two patients (13.3%) in the PTFE group, and eight
      patients (42.1%) in the non-PTFE group. Mitral valve repair with PTFE showed
      better results than conventional mitral valve repair without PTFE during the mean
      follow-up period of 23 months.

PMID- 9557280
TI  - [Dor operation for end-stage ischemic cardiomyopathy].
AB  - Endoventricular circular patch plasty (Dor operation) was used to treat end-stage
      dilated ischemic cardiomyopathy in 13 patients from January to December, 1997.
      There were 10 men and three women aged from 57 to 78 years (mean 63 years).
      Single, double, triple and left main trunk coronary disease was present in one,
      two, eight and two patients, respectively. Mean ejection fraction was 22% (6-30%)
      and signs of congestive heart failure were clear in all patients [New York Heart
      Association (NYHA) class III in eight patients and class IV in five patients].
      Angina pectoris was present in five patients. Six patients had associated
      significant mitral regurgitation. Coronary artery bypass grafting (mean 3.2
      grafts) was used in 11 patients and mitral valve reconstruction was performed in
      6 patients (4: replacement and 2: repair) combined with akinetic area exclusion
      by the Dor technique. All patients were successfully weaned from cardiopulmonary
      bypass without mechanical support and no perioperative death occurred. Three
      patients died in hospital at 1-2 postoperative months due to pneumonia, stroke
      and heart failure, respectively. Two patients died during the late period due to
      stroke and sudden death. Among the eight survivors, six patients were in NYHA
      class I-II and two patients in class III. Ejection fraction increased from 22% to
      36%, end-diastolic and systolic volume indices decreased from 168 +/- 58 to 123
      +/- 39 ml/m2 and from 131 +/- 60 to 81 +/- 33 ml/m2, respectively. Pulmonary
      capillary wedge pressure decreased from 19 +/- 10 to 14 +/- 5 mmHg. The Dor
      procedure is an effective surgical alternative for patients with end-stage
      ischemic cardiomyopathy who are considered to be candidates for cardiac
      transplantation.

PMID- 9557281
TI  - [Randomized, double-blind, placebo-controlled study of supplemental vitamin E on
      attenuation of the development of nitrate tolerance].
AB  - The attenuation of intracellular production of cyclic guanosine monophosphate
      (cGMP) has been known as a mechanism of nitrate tolerance. A recent in vitro
      study have shown an increase in superoxide levels and a reduced activation of
      guanylate cyclase in tolerant vessels. We investigated the preventive effect of
      an antioxidant, vitamin E, on the development of nitrate tolerance. In this
      double-blind, placebo-controlled study, 24 normal volunteers and 24 patients with
      ischemic heart disease (IHD patients) were randomized to receive either vitamin E
      (200 mg t. i. d.; vitamin E group) or placebo (placebo group). Vasodilator
      response to nitroglycerin was assessed with forearm plethysmography by measuring
      the change in the forearm blood flow before and 5 min after sublingual
      administration of 0.3 mg nitroglycerin, and at the same time, blood samples were
      taken from veins to measure the platelet cGMP level. Measurements of the forearm
      blood flow and blood sampling were obtained serially at baseline (day 0), 3 days
      after taking vitamin E or placebo alone (day 3), and 3 days after application of
      a 10 mg/24 hr nitroglycerin tape concomitantly with oral vitamin E or placebo
      (day 6). The response of forearm blood flow (%FBF) and cGMP (%cGMP) after
      sublingual nitroglycerin on day 0(%FBF: normal volunteers 32 +/- 12% vs 31 +/-
      11%, IHD patients 35 +/- 15% vs 34 +/- 15%; %cGMP: normal volunteers 38 +/- 10%
      vs 35 +/- 11%, IHD patients 37 +/- 11% vs 38 +/- 12%; vitamin E group as placebo
      group) and day 3(%FBF: normal volunteers 33 +/- 9% vs 32 +/- 12%, IHD patients 35
      +/- 12% vs 33 +/- 13%, %cGMP: normal volunteers 38 +/- 10% vs 37 +/- 11%, IHD
      patients 36 +/- 14% vs 37 +/- 10%, vitamin E group vs placebo group) were not
      different between the two groups. On day 6 %FBF and %cGMP in the placebo group
      were significantly lower compared with day 0, and there were significant
      differences in them between the two groups (%FBF: normal volunteers 30 +/- 12% vs
      17 +/- 9%, p < 0.01; IHD patients 28 +/- 14% vs 17 +/- 8%, p < 0.01; %cGMP:
      normal volunteers 35 +/- 11% vs 8 +/- 5%, p < 0.01; IHD patients 38 +/- 10% vs 12
      +/- 4%, p < 0.01, vitamin E group vs placebo group). In conclusion, the
      combination therapy with vitamin E is potentially a useful method to prevent the
      development of nitrate tolerance.

PMID- 9557282
TI  - [Radioimmunoimaging of aortic dissection and acute bowel infarction with
      radiolabeled [correction of radioiodinated] murine antismooth muscle myosin
      antibody.

PMID- 9557283
TI  - [Enhanced expression of hepatocyte growth factor/c-Met by myocardial ischemia and
      reperfusion in a rat model].

PMID- 9557284
TI  - [Upregulation of angiotensin-converting enzyme during the healing process after
      injury at the site of percutaneous transluminal coronary angioplasty in humans].

PMID- 9557285
TI  - [In vivo gene transfection with heat shock protein 70 enhances myocardial
      tolerance to ischemia-reperfusion injury in rat].

PMID- 9557286
TI  - [Cardiovascular imaging in-a-month. A 51-year-old man with acute abdomen].

PMID- 9557287
TI  - [References cited in literature].

PMID- 9557288
TI  - Epidemiological study and genetic analysis of GB virus C infection in general
      population from an area endemic for hepatitis C.
AB  - The aim of this work was to study the prevalence, potential risk factors,
      clinical and laboratory features of GB virus C (GBV-C) infection in general
      population from an area endemic for hepatitis C. A reverse transcriptase
      polymerase chain reaction (RT-PCR) for detection of GBV-C RNA was used to examine
      the prevalence of GBV-C RNA in both hepatitis C virus (HCV) endemic (R town) and
      nonendemic areas (M town) in Yamagata prefecture, Japan. In R town, GBV-C RNA was
      detected in 23 (2.9%) out of the 800 residents, whereas anti-HCV and HCV-RNA were
      found in 226 (28.3%) and 163 (20.4%), respectively. The prevalence of GBV-C RNA
      in R town (2.9%) was higher than that in M town (1.0%), although the difference
      was not statistically significant. The individuals with anti-HCV had
      significantly higher frequency of active GBV-C-infection than those without anti
      HCV in both towns. No evidence indicating that GBV-C infection affected the
      severity of hepatitis C was obtained. The multivariate analysis revealed that the
      young anti-HCV positive individuals with a history of blood transfusion had
      higher incidence of active GBV-C infection. The phylogenetic analysis showed that
      the GBV-C isolates from both R and M towns were divided into two separate branch
      groups designated HG and Asia GB groups.

PMID- 9557289
TI  - Prevalence of hepatitis B, hepatitis C, and GB virus C/hepatitis G virus
      infections in liver disease patients and inhabitants in Ho Chi Minh, Vietnam.
AB  - The prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and GB virus
      C or hepatitis G virus (GBV-C/HGV) infections was determined in 289 patients with
      liver disease in Ho Chi Minh City and 890 healthy inhabitants of its rural area,
      Dalat City, Vietnam, respectively. Serum HCV RNA and GBV-C/HGV RNA were detected
      by reverse transcription-polymerase chain reaction (RT-PCR). HBsAg, HCV
      antibodies, and GBV-C/HGV RNA were detected in 139 (47%), 69 (23%), and ten (3%)
      subjects, respectively, often accompanied by elevated serum levels of alanine
      aminotransferase. HBsAg and HCV antibodies or HCV antibodies and GBV-C/HGV RNA
      were detectable simultaneously in 8% and 2% of the patients, respectively. In the
      inhabitants, HBsAg, HCV antibodies, and GBV-C/HGV RNA were found in 51 (5.7%),
      nine (1.0%), and 11 (1.2%) subjects, respectively. Thus, the prevalence of HBsAg,
      HCV antibodies, and GBV-C/HGV RNA was significantly higher in liver disease
      patients than those in the general population. In the samples from 69 patients
      and nine inhabitants who were seropositive for HCV antibodies, HCV RNA was
      detectable in 42 (61%) and 4 (44%), respectively. In patients with liver disease,
      ten belonged to HCV genotype 1a, ten to HCV 1b, three to HCV 2a, four to HCV 2b,
      and two to HCV 3a by PCR with genotype-specific primers. Nine patients had mixed
      genotypes, and the remaining four were not classified. Of the GBV-C/HGV RNA
      positive individuals, two patients and two inhabitants were positive for HBsAg,
      while none of the residents had HCV antibodies, although six HCV antibodies (60%)
      and four HCV RNA (40%) were found in patients. When a phylogenetic tree of GBV
      C/HGV was constructed based on the nucleotide sequences, the 21 isolates were
      classified into at least two genotypes; four isolates belonged to G2, and 17 to
      G3. The results indicate that in Ho Chi Minh HCV infection prevails with broad
      distribution of genotypes together with HBV infection among patients with liver
      disease. This study suggests that GBV-C/HGV infection occurs independently in the
      two different districts in association with HCV infection.

PMID- 9557290
TI  - Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis
      C virus-infected chronic hepatitis patients.
AB  - Human hepatitis B virus (HBV) and hepatitis C virus (HCV) are two major etiologic
      agents of chronic hepatitis, which is closely related to the development of
      hepatocellular carcinoma (HCC). A possible involvement of HBV co-infection was
      investigated in ongoing HCV-related liver diseases in HCV-infected patients. A
      prevalence of anti-HBc in anti-HCV-positive/HBsAg-negative chronic hepatitis
      patients and a low copy number of HBV DNA were found in most of the liver biopsy
      samples of anti-HCV-positive/HBsAg-negative patients. The present data suggest
      that HBV co-infects frequently with HCV and may play an important role in the
      development of HCC in the anti-HCV-positive/HBsAg-negative patients with chronic
      hepatitis.

PMID- 9557291
TI  - Genetic complexity of the hypervariable region 1 (HVR1) of hepatitis C virus
      (HCV): influence on the characteristics of the infection and responses to
      interferon alfa therapy in patients with chronic hepatitis C.
AB  - HCV exists within its host as pools of related genetic variants referred to as
      quasispecies. The hypervariable region 1 (HVR1) of the E2 envelope gene is
      subjected to strong selective pressure from neutralizing antibodies. The genetic
      complexity of this region is defined as the total number of genetic variants
      within the quasispecies population. The genetic complexity of the HVR1 region was
      examined in patients with chronic hepatitis C and its relationship with the
      epidemiology of HCV infection, and its influence on liver disease and the
      response to interferon treatment were determined in 114 patients with chronic
      hepatitis C. The genetic complexity of the HVR1 major variants was measured
      before treatment by using a polymerase chain reaction (PCR)-single-strand
      conformation polymorphism (SSCP) technique, and was compared with
      epidemiological, clinical, virological and histological features. The patients
      were treated with 3 megaunits of interferon (IFN) alfa for 3 to 6 months and the
      response to treatment was assessed at 3, 6 and 12 months. The HVR1 could be
      studied in 101 of the 114 patients (89%). Genetic complexity was significantly
      higher in patients infected through blood transfusion than intravenous drug use
      (mean complexity index: 5.7 +/- 2.3 vs. 4.7 +/- 1.5, respectively; P = 0.04).
      This relationship was independent of age and the estimated time since infection.
      No significant relationship was found with other parameters of infection or liver
      disease. In univariate analysis, the genetic complexity of HVR1 major variants
      did not affect the rates of ALT normalization at months 3 and 6 of IFN treatment.
      HVR1 genetic complexity was lower in patients with a sustained virological
      response than in non-responders (4.0 +/- 1.7 vs. 5.4 +/- 2.0, respectively; P =
      0.07). In multivariate analysis of pretreatment parameters associated with a
      sustained virological response to treatment, three parameters appeared to be
      independent predictors of such a response: a low viral load (P < 0.04), a low
      anti-HCV core IgM titer (P = 0.03) and a low genetic complexity of HVR1 major
      variants (P < 0.04). In conclusion, the HVR1 of HCV has a quasispecies
      distribution in infected individuals. Its genetic complexity is significantly
      higher in transfusion recipients than in intravenous drug users, suggesting that
      the size of the initial inoculum affects the later emergence and development of
      viral quasispecies. The genetic complexity of HVR1, together with viral load and
      the anti-HCV IgM titer, are independent predictors of a sustained virological
      response to IFN alfa in patients with chronic hepatitis.

PMID- 9557292
TI  - Predominance of HCV type 2a in saliva from intravenous drug users.
AB  - Paired serum and saliva samples were collected simultaneously from 50 intravenous
      drug users with serologically proven hepatitis C virus infection. The oral health
      of the volunteers was also assessed. Hepatitis C virus RNA was detected by nested
      PCR, employing primers from the 5' noncoding region. Positive PCR products were
      sequenced using the Sequenase PCR Product Sequencing Kit (Amersham Life
      Sciences). HCV RNA was detected in 33 (66%) of the 50 serum samples. HCV RNA was
      detected in 19 (57.6%) of the corresponding 33 saliva samples. There was no
      correlation between oral health status or HIV seropositivity and the detection of
      HCV in saliva. However, subjects with HCV in their saliva were significantly more
      likely to complain of xerostomia (P < 0.05). Isolate genotypes were identified in
      paired serum and saliva of 15 intravenous drug users. HCV genotypes 1, 2, 3 and 6
      were detected in both specimens. In seven cases, a differing HCV genotype was
      found in serum compared to the paired saliva specimen. The distributions of
      genotypes in serum and saliva were very different, with genotype 2a more common
      in saliva than serum (P < 0.005). These data suggest that in some cases the
      source of salivary HCV may not be serum transudation along the periodontal
      membrane or across damaged mucosa, and that an alternative local source, possibly
      the salivary glands themselves, should be considered.

PMID- 9557293
TI  - Serological evidence of SV40 infections in HIV-infected and HIV-negative adults.
AB  - SV40 is a simian polyomavirus that was a contaminant of some viral vaccines
      administered to people between 1955 and 1962. SV40 DNA has recently been found
      associated with several types of human tumors, suggesting that the virus is
      present in humans. We examined sera from patients infected with human
      immunodeficiency virus type 1 (HIV-1) as well as from HIV-1-negative controls to
      determine the prevalence of SV40 neutralizing antibodies using a specific plaque
      reduction assay. We found that 16.1% of HIV-infected patients (n = 236) were
      seropositive for SV40, as compared to 12.0% of HIV-negative control volunteers (n
      = 108) and 11.1% of HIV-negative patients (n = 72). These differences were not
      statistically significant. As individuals born between 1941 and 1962 had the
      highest chance of having received SV40-contaminated poliovaccines, we analyzed
      SV40 seropositivity rates based on year of birth. SV40 antibody rates for HIV
      infected patients born before 1941, between 1941 and 1962, and after 1962 were
      17.1%, 16.3%, and 11.8%, respectively. For the HIV-negative subjects, the rates
      were 12.5%, 12.0%, and 9.7%, respectively. There was no correlation between SV40
      seropositivity and either the stage of disease in HIV-infected patients or the
      race/ethnicity. Also, there was no correlation between the presence of SV40
      neutralizing antibody and the titer of neutralizing antibody to human
      polyomavirus BKV. The SV40 seropositivity rates in the patients born between 1941
      and 1962 may be explained by the likelihood of those individuals having received
      SV40-contaminated vaccines, but the detection of SV40 neutralizing antibody in
      individuals born after 1962 (with no risk of having received contaminated
      vaccines) is significant. Although cross-reactive antibodies might theoretically
      contribute to the observed reactivities, these results suggest that SV40
      neutralizing antibodies are present in certain individuals and raise the
      possibility that SV40 continues to infect humans long after vaccines were freed
      from contamination.

PMID- 9557294
TI  - Evaluation of an expanded two-ELISA approach for confirmation of reactive serum
      samples in an HIV-screening programme for pregnant women.
AB  - Serum specimens were collected from 31,232 pregnant women in Amsterdam between
      1988 and 1995 in a screening programme for human deficiency virus (HIV)
      infection. The sera of 56 (0.179%) women tested were confirmed as positive for
      HIV. A total of 67 sera reacted positive or borderline by the screening enzyme
      linked immunosorbent assay (ELISA) and indeterminate or negative by HIV-1 Western
      blot; 42 of these specimens were available for evaluation of the strategy for
      diagnosis of HIV infection. A two-ELISA approach with the second ELISA based on a
      principle different from that of the screening ELISA, expanded with the use of a
      membrane immunoassay based on two synthetic peptides specific for HIV-1 gp41 and
      HIV-2 gp36 envelope proteins, was compared with the Western blot analysis.
      Indeterminate results were resolved with a nucleic acid sequence-based
      amplification assay (NASBA) for HIV-1 RNA and a strip immunoassay (SIA) for the
      simultaneous detection of antibodies to HIV-1 or HIV-2 and HIV-1 p24 antigen.
      Eleven samples were weakly or borderline positive by the screening test and gave
      indeterminate results by Western blot. The expanded two-ELISA approach designated
      these sera as HIV-negative, and confirmed negative by NASBA and the SIA. Twenty
      one samples showed borderline or positive results on the screening test and
      negative results by Western blot. Again, these sera were characterised as HIV
      negative by the expanded two-ELISA procedure, and this characterisation was
      confirmed by both NASBA and the SIA. Five HIV-2-positive serum samples were
      recognised by the expanded two-ELISA approach and the SIA; these sera were
      negative by NASBA. Finally, another five serum samples were weakly or borderline
      positive by both ELISAs and positive by the membrane immunoassay; of these five,
      two sera generated positive patterns and the other three indeterminate patterns
      on Western blots, and four were positive by the NASBA assay. Follow-up serum
      specimens from these five women were negative and the reactivity of the initial
      specimens was thus likely to have been the result of cross-contamination. Our
      results demonstrate the effectiveness of a simple confirmation approach of two
      HIV ELISAs expanded with a membrane spot assay to discriminate between infection
      with HIV-1 or HIV-2. The data also indicate the importance of retesting
      individuals with indeterminate or positive confirmational results to exclude the
      possibility of contamination as the cause of reactivity of the original specimen.

PMID- 9557295
TI  - Molecular epidemiology of adenovirus type 7 in Israel: identification of two new
      genome types, Ad7k and Ad7d2.
AB  - The molecular epidemiology of Adenovirus type 7 in Israel was investigated. Fifty
      seven adenovirus isolates identified as serotypes 7 or 7a which were recovered
      from patients in Israel between 1968 and 1995 were analyzed by restriction
      enzymes digestion using BamHI for primary discrimination and identification of
      genome types and by six additional enzymes: BstEII, HpaI, BglI, BglII, BclI, and
      XbaI for confirmation and determination of genomic subtypes. Four digestion
      patterns were identified with BamHI; one of them was new. Using BstEII, two
      patterns were obtained, one of them new. Digestion with the other five enzymes
      yielded known patterns. The analysis revealed four different genomic types and
      subtypes, which circulated in Israel in different years: subtype 7a1; type 7b, a
      type with a new BamHI pattern which was designated type 7K, and a subtype with a
      new BstEII pattern which differed from type 7d by one restriction site and was
      designated type 7d2. Twenty-two isolates from 1968 through 1975 and from 1984
      were Ad7a1. Three isolates from 1973-1974 were Ad7b. Five isolates from 1968
      through 1973 were Ad7K and 27 isolates from 1992 through 1995 were Ad7d2. This
      demonstrates the temporal change in the circulating genome types with up to three
      genome types cocirculating in 1 year (1973). The two new types, Ad7k and Ad7d2
      could have evolved in Israel or could have been imported by travellers and
      immigrants from neighboring or distant countries.

PMID- 9557296
TI  - Consistent polymerase chain reaction-single-strand conformation polymorphism
      pattern of human herpesvirus-8 in the course of classical Kaposi's sarcoma
      assumes its clonal origin.
AB  - There is emerging evidence that Kaposi's sarcoma-associated herpesvirus (KSHV or
      HHV-8) has a central role in the pathogenesis of Kaposi's sarcoma (KS). The
      occurrence of HHV-8 in classical KS biopsies is reported irrespective of its
      clinical stage (patch, plaque, nodular). HHV-8 was detected in 25 of 28 formalin
      fixed paraffin-embedded classical KS samples by nested polymerase chain reaction.
      In addition, in six patients multiple tumors were available (n = 21). Single
      strand conformation polymorphism (SSCP) analysis of the amplicons showed uniform
      SSCP pattern of samples belonging to the same patient regardless of whether the
      KS was multiplex or developed again years after the first excision. Most of the
      SSCP patterns were confirmed by further sequence analysis. The presence of the
      same sequence variant of HHV-8 in various samples of the same patient supports
      the clonal origin of classical Kaposi's sarcoma.

PMID- 9557297
TI  - Homotypic and heterotypic IgG and IgM antibody responses in adults infected with
      small round structured viruses.
AB  - Antibody responses to recombinant Norwalk (rNV) and Mexico (rMXV) viral capsid
      proteins were studied in 39 adults involved in outbreaks of gastroenteritis
      associated with genogroup 2 small round structured viruses (SRSVs). Nineteen
      individuals were involved in outbreaks associated with MXV-like strains and 20 in
      outbreaks associated with four other genogroup 2 SRSVs. IgG antibodies were
      measured in acute and convalescent sera using indirect enzyme-linked
      immunosorbent assay (ELISA), and IgM was measured by indirect and capture ELISAs.
      Nineteen (49%) patients demonstrated a significant rise in IgG to rMXV with four
      (10%) patients also showing anamnestic responses to rNV. Fourteen patients were
      positive in the rMXV IgM-capture ELISA, representing 74% of patients
      demonstrating IgG rises. IgG and IgM responses to rMXV were observed in both
      groups, although higher levels of responses were seen in adults infected with MXV
      like strains than those infected with non-MXV genogroup 2 viruses. No significant
      IgM responses were observed to rNV. These results indicate that, following SRSV
      infection, adults show a rise in antibody which is broadly reactive to viruses
      within but not between genogroups, although greater homotypic than heterotypic
      responses are produced. These findings have implications for interpretation of
      seroepidemiological studies and serodiagnosis of SRSV infections using
      recombinant capsids.

PMID- 9557298
TI  - Transport of viruses through fetal membranes: an in vitro model of perinatal
      transmission.
AB  - A model system for perinatal transmission of viral infections was developed and
      transport of infectious virus particles through fetal membranes was investigated.
      Viruses of different families known to cause serious intrauterine infections were
      selected, including relevant and model viruses: the DNA-viruses HSV-1 and -2 as
      well as the animal herpes viruses BHV-1 and SHV-1, the RNA-virus BVDV as a model
      for hepatitis C virus, HIV-1 and -2, and PPV as a model for parvovirus B19.
      Migration of infectious virus from the maternal to the fetal side of the membrane
      could be detected as early as 20 min after the start of incubation. A peak of
      virus migration was observed after 1-2 hr. 0.02-1% of HSV-1 and 0.03-0.2% of HSV
      2 were transported from the maternal side of the membrane to the fetal side. Only
      0.01% of PPV migrated to the fetal side, whereas no transport of BVDV was
      observed. HIV-1 (1.4%) and HIV-2 (0.8%) seemed to be transported at higher rates.
      The concept of an active transport of infectious virus is compatible with the
      kinetics of penetration of the fetal membrane. The question of whether different
      receptors for the individual viruses on the cellular surface account for
      differences in virus transport will require further investigation. The fetal
      membrane acts as a protective barrier for the fetus, reducing greatly infectious
      titers or even preventing completely penetration of virus.

PMID- 9557299
TI  - Detection of respiratory syncytial virus RNA in blood of neonates by polymerase
      chain reaction.
AB  - During the winter season of 1994/1995, nasopharyngeal aspirates and blood samples
      of neonates who were admitted to the Neonatal Intensive Care Unit (NICU) (group
      1) and infants with respiratory tract disease (group 2) were examined
      prospectively for the presence of respiratory syncytial virus (RSV). Examination
      of nasal washes were done by antigen detection and blood samples were tested by
      nested reverse transcription and polymerase chain reaction (RT-PCR). The results
      of the 41 neonates studied were as follows: 14/41 were positive for RSV antigen
      in nasal washes and for RSV-RNA in blood, 5/41 were only RSV antigen positive,
      13/41 neonates had negative nasal washes; 6 had positive RT-PCR results in blood.
      In 9/41 cases only blood samples were available. Five of these were positive by
      RT-PCR testing. Group 2 included 20 infants hospitalized with respiratory tract
      disease, e.g., pneumonia, bronchiolitis, or Upper Respiratory Tract Infection
      (URTI). Eleven out of twenty were positive for RSV antigen in nasal washes and
      6/20 were also positive for RSV-RNA in blood. The conclusion is that viremia may
      be a frequent occurrence in neonates and young children.

PMID- 9557300
TI  - [The study of ototoxicity in Gallus domesticus by recording distortion products].
AB  - Distortion products (DP) were recorded and a morphological cochlear study was
      made of a sample of 60 ears from chickens (Gallus domesticus. Leghorn breed) and
      the ages of 15, 23, 29 and 60 days, after intoxication by intramuscular
      gentamicin injection (40 mg per kg weight and day for 8 days). Spontaneous or
      transitory otoacoustic emissions were not obtained in any case. DP recordings
      showed a 2F1-F2 response in every frequency band ranging from 0.7 to 6 KHz. The
      DP incidence shifted with the age of the chickens and differed significantly (p <
      0.001) in the groups of 29 and 60 day-old chickens (m = 100%) and in the 29-day
      old (m = 64%) and 60-day-old (m = 62%) intoxicated chickens. We found no
      significant differences in DP amplitude in subpopulations. In the intoxicated
      groups, the proximal segment of the ototic membrane disappeared in the macula
      lagenae and a loss of contact with the hair cells appeared. Degenerative vacuolar
      phenomena were observed in the support cells and cellular loss in the spiral
      ganglion.

PMID- 9557301
TI  - [Changes in the middle ear mucosa of the Wistar rat after experimental resection
      and obstruction of the eustachian tube].
AB  - Eustachian tube (ET) disfunction, alone or combined with other factors, is the
      main source of middle ear pathogenesis and can lead to other physiopathological
      events that originate disease (serous otitis media, adhesive otitis,
      cholesteatoma). In seven Wistar rats (study group), experimental mechanical
      obstruction of the left Eustachian tube was performed. Using an anterior cervical
      incision, the osteocartilaginous junction of the ET was severed and obliterated
      with a bit of muscle in order to prevent rechanneling. After a period of six
      months, the middle ear mucosa was removed for histological study. Comparisons
      were made of the experimental ear and the opposite ear, as well as the ears of
      three rats in the control group. We compared our findings with those of other
      authors and reviewed experimental animal models of serous otitis media and
      cholesteatoma that have been used to study the influence of ET in middle ear
      disease.

PMID- 9557302
TI  - [Cochlear implants in post-lingual persons: results during the first five years
      of the clinical course].
AB  - Abundant literature is available on the results of cochlear implants in
      postlingual persons. Nevertheless, there are few long-term studies with a follow
      up of more than 1 year. We present the outcomes of 37 postlingual patients with a
      5-year follow-up period. We examined the modifications that occurred with changes
      in coding strategy (MPEAK-SPEAK). After activation, the coding strategy was SPEAK
      in 10 patients. MPEAK in 20: 7 other SPEAK had changed from MPEAK. Significant
      improvement (p < 0.01) was observed in all the tests in the first 6 months.
      Subsequent assessments revealed a constant improvement in all tests. The results
      were statistically significant (p < 0.05) for vowels, consonants and bisyllables.
      Performance with the SPEAK strategy was better than with MPEAK. These results
      were statistically significant for consonants (p < 0.05), monosyllables (p <
      0.05) and bisyllables (p < 0.01). We concluded that the results of postlingual
      patients after cochlear implantation showed clear benefits of these devices in
      profound bilateral deafness, better results with the SPEAK coding strategy than
      with MPEAK and constant improvement in results, even after the first year of
      surgery.

PMID- 9557303
TI  - [The study of otoacoustic emissions in diabetes mellitus].
AB  - Cochlear activity was evaluated by means of otoacoustic emission in patients with
      normal hearing and insulin-dependent diabetes mellitus. Twenty diabetic subjects
      were studied by recording click evoked otoacoustic emissions (TEOAE) and
      distortion products otoacoustic emissions (DPOAE) 2fl-f2 and comparing the
      results with those obtained in a control group of non-diabetic with normal
      hearing. The results obtained in the diabetic group showed a statistically
      significant decrease in mean amplitude, in the amplitude of every click evoked
      otoacoustic emissions and in the mean amplitudes of various distortion products
      compared with the control group. These findings suggest the presence of cochlear
      disorders in diabetic patients, probably produced by impaired functional
      properties of the outer hair cells.

PMID- 9557304
TI  - [Endonasal dacryocystorhinostomy. A comparative study of microscopic and
      endoscopic techniques].
AB  - A comparative study was made of endonasal dacryorhinostomy using either a 0
      degree or 30 degrees rigid endoscope or a Zeiss operating microscope in 25
      patients with chronic epiphora and complete stenosis of the nasolacrimal duct
      confirmed by dacryocystography. The success rate in both groups was similar
      (80%). Computed tomography is useful in post-traumatic cases.

PMID- 9557305
TI  - [Morphological comparative imaging study of the pharynx in patients with
      obstructive sleep apnea syndrome (OSAP), healthy snorers and controls].
AB  - A morphological study was made of the pharynx of 106 subjects, including obese
      and non-obese patients with obstructive sleep apnea syndrome (OSAS), obese and
      non-obese healthy snorers and controls. A CT scan was made of each subject and
      the luminal area was measured on all sections. The influence of obesity on airway
      size was determined. Airway lumina generally were narrower in patients with OSAS,
      of intermediate size in healthy snorers, and widest in controls. Luminal
      narrowing was the result of increased pharyngeal wall thickness and directly
      related to the degree of obesity. This pattern was evident throughout the
      pharynx, except for the hypopharynx, where the airway size was similar in all the
      patients studied.

PMID- 9557306
TI  - [Bacteriology in infectious and obstructive adenoid-tonsillar pathology].
AB  - Infectious and obstructive adenotonsillar processes are common in the pediatric
      population. Bacteriological and serological studies were made of acute
      tonsillitis, recurrent acute tonsillitis with tonsillar hypertrophy, and
      tonsillar hypertrophy. Positive cultures were more frequent in tonsils than in
      adenoids. Pathogenic microorganisms were isolated more often in infectious than
      in obstructive processes. Anti-streptococcal antibody titers were raised in
      infectious processes, but remained within normal limits in obstructive processes.
      Serum total IgE levels were similar in both processes. These findings show that
      tonsillar hypertrophy is not related directly with microorganisms or atopic
      pathology.

PMID- 9557307
TI  - [Surgery of the laryngeal framework: type I thyroplasty].
AB  - Eight type I thyroplasties were performed. All the patients had a breathy voice
      related with unilateral vocal cord paralysis. Several causes were involved. All 8
      patients achieved good glottic closure and the free edges of the vocal cords mi
      closed uniformly. Acoustic parameters were studied using Dr. Speech version 2.0
      for Windows. The SPSS program was used for statistical analysis. The study showed
      significant improvement in maximum phonation time, shimmer, and normalized noise
      energy. Modifications in the surgical technique are discussed.

PMID- 9557308
TI  - [Lateral cervical branchial cysts: a retrospective study].
AB  - The cause of lateral cervical branchial cysts is debated. Some authors claim that
      they are congenital, whereas others believe that they are acquired, being their
      likely origin cystic degeneration of the cervical lymph nodes. Their protocol of
      study and differential diagnosis with respect to malignant neck masses are of
      special interest. A retrospective clinical study was made of 13 cervical
      branchial cysts seen by one of the authors over a decade-long period. Based on
      the results, their probable origin is discussed and a study protocol is proposed.
      Although it has been discussed by some authors, we conclude that the origin of
      branchial cysts cannot be determined through this type of clinical study.
      Computed tomography and fine-needle aspiration currently are essential diagnostic
      methods in the study protocol of these lesions.

PMID- 9557309
TI  - [Incomplete ciliary axonema: anther cause of ciliary dysmotility syndrome?].
AB  - Immotile cilia syndrome is associated with different ciliary defects, although
      the clinical presentation is similar in every case. A study was made of a 36-year
      old woman with recurrent respiratory infections since birth, chronic sinusitis
      and chronic bronchitis with bronchiectasias. Her medical history included a
      tubaric pregnancy and two miscarriages. Nasal mucociliary transport was
      investigated on two occasions at a 1-year interval using an isotopic technique.
      Ciliary ultrastructure was studied by electron microscopy after obtaining two
      biopsies from the inferior and middle turbinates separated by a 1-year interval.
      The sweat test and blood immunoglobulins were normal. The absence of mucociliary
      transport was verified on both occasions. An abnormality was observed in 30% of
      the cilia in the form of semicircular ciliary cross-sections, with only 7 pairs
      of peripheral microtubules. The central pair was normal. We termed this anomaly
      "incomplete ciliary axonema" and believe that it could be another cause of
      immotile cilia syndrome.

PMID- 9557311
TI  - [Mastoid osteosarcoma].
AB  - A case of osteogenic sarcoma of the mastoid region of the temporal bone in a 28
      year-old male is reported. The rarity of the site is emphasized and the
      fundamental clinical and therapeutic features are discussed. The literature is
      reviewed.

PMID- 9557310
TI  - [Cholesteatoma of the external ear canal. A case report].
AB  - Cholesteatoma of the external ear canal is rare in otological practice. The case
      of a 62-year-old woman with local extension but scant symptoms or signs is
      reported. The literature is reviewed and the cause and treatment are discussed.

PMID- 9557312
TI  - [Dysphagia in Forestier's disease (vertebral ankylosing hyperostosis)].
AB  - Forestier's disease is characterized by the formation of vertebral bridges which
      joint the ventral aspect of the vertebral bodies by ossification of the anterior
      vertebral longitudinal ligament. A 58-year-old man with idiopathic ankylotic
      hyperostosis had pronounced osteophytosis of the neck that produced the unusual
      symptom of dysphagia. The literature is reviewed and the pathogenic criteria,
      diagnosis, and therapy are discussed.

PMID- 9557313
TI  - [Laryngeal paraganglioma].
AB  - A case of laryngeal paraganglioma in a 65-year-old male was treated by
      supraglotic laryngectomy. This controversial tumor is analyzed and guidelines are
      given for its clinical and histological (immunohistochemical) diagnosis and
      treatment.

PMID- 9557314
TI  - [Small cell carcinoma of the parotid gland. A case report].
AB  - A case of small-cell carcinoma (SCC) of the parotid gland in an 82-year-old woman
      is reported. SCC arising in major salivary glands are extremely rare. By
      immunohistochemical study, this case was classified as a small-cell carcinoma
      with neuroendocrine differentiation. These neoplasms seem to have a far better
      prognosis than those arising from the bronchial tree. Treatment is mainly local
      and regional surgery with complementary radiotherapy.

PMID- 9557316
TI  - Ultrasonographic study of feline lower urinary tract diseases: 32 cases.
AB  - The objective of the study was to describe the ultrasonographic findings of
      urinary bladder urolithiasis and to determine the diagnostic value of the
      technique in feline lower urinary tract diseases (LUTD). Physical examination of
      the urinary system and routine clinicopathological analysis of the blood and
      urine were performed on 32 cats presented with clinical symptoms of LUTD.
      Cystosonography was done on all of the cats, while plain radiography was
      performed on 8 and double contrast cystography on 2 cats. Sonography of the
      bladder provided the following diagnoses: urolithiasis and chronic cystitis: 24
      cases, chronic cystitis without urolithiasis: 4 cases, bladder neoplasm: 1 case,
      negative sonographic finding: 3 cases. Bladder calculi and/or plugs were
      diagnosed easily, up to a size of 2 mm, according to acoustic shadowing and/or
      reverberation and gravitation. When the bladder was empty, it was filled up with
      physiologic saline solution to visualise its contents more easily. Sonography
      proved to be a useful technique for diagnosing urinary bladder calculi and/or
      plugs even when they were radiolucent and for distinguishing among the different
      causes of LUTD. Although ultrasonography is a valuable diagnostic tool,
      radiography is still necessary to explore lower urinary tract diseases,
      especially when cystosonography provides negative results or urethral obstruction
      is suspected.

PMID- 9557315
TI  - [Post-laryngectomy tracheomalacia. The use of self-expandable metal prostheses].
AB  - Tracheomalacia is an uncommon disorder in laryngectomized patients, but it is an
      important therapeutic problem. Self-expandable metal prostheses can be used in
      its treatment. We report the successful implantation of two tracheal prostheses
      in a laryngectomized patient.

PMID- 9557317
TI  - Ultrasonographic findings of renal dysplasia in cocker spaniels: eight cases.
AB  - A retrospective study of eight young Cocker Spaniels aged 9-24 months was
      performed to describe the ultrasonographic findings of histologically confirmed
      renal dysplasia. Ultrasonography revealed kidneys of significantly (p < 0.001)
      reduced volume in all dogs. During qualitative evaluation, two different types of
      sonographic alterations could be seen. In one type of the ultrasound alterations,
      corticomedullary demarcation was distinct and the renal cortex was remarkably
      thin, which was best seen in the dorsal (frontal) imaging plane. In the other
      type of the ultrasound appearance, overall increased echogenicity with poor
      corticomedullary demarcation was noticed, and the kidneys could hardly be
      separated from their surroundings. These features were best recognised in the
      sagittal (coronal) imaging plane. In one dog with secondary hypercalcaemia, a
      hyperechoic corticomedullary area was also seen. Post-mortem histological
      diagnosis revealed renal dysplasia and secondary fibrosis. Based on ultrasound
      findings alone, renal dysplasia (renal familial disease) can be suspected when
      small kidneys with thin echogenic cortex are present in young dogs. An ultrasound
      image, similar to that of fibrotic kidneys (increased overall echogenicity and
      reduced corticomedullary definition) cannot be differentiated from chronic
      inflammatory disease and from end-stage kidneys. Therefore, ultrasound-guided
      biopsy or post-mortem histology is necessary for the definitive diagnosis of
      renal dysplasia. This is the first study reporting on the ultrasound appearance
      of renal dysplasia in Cocker Spaniel dogs.

PMID- 9557318
TI  - Diagnostic value of certain mastitis markers in following up the clinical and
      bacteriological changes in pharmacotherapeutic studies.
AB  - Trends of certain mastitis markers were studied in udder quarters (n = 201)
      showing clinical symptoms of acute mastitis. Besides the clinical examination,
      before the first treatment (baseline sample), and about 3 weeks later, 17 to 24
      days following the last treatment (control sample) milk samples were collected
      for bacteriological identification of the mastitis pathogens and for the
      determination of certain inflammatory markers: somatic cell count (SCC), N-acetyl
      beta-D-glucosaminidase (NAGase) and alpha 1-antitrypsin (ATR) activities, as well
      as bovine serum albumin (BSA) and chloride (Cl-) concentrations. Based upon the
      clinical and bacteriological status as well as the SCC recorded at the control
      investigations, 6 groups were established (recovered, latently infected,
      subclinical mastitis: bacteriologically positive and negative, as well as
      clinical mastitis: bacteriologically positive and negative). As compared to the
      baseline samples, all parameters decreased in the case of recovered udder
      quarters, as well as in those with abated latent infection or subclinical
      mastitis at the time of control examination. Comparing the control samples of the
      different categories, characteristic differences were found in NAGase activity,
      indicating the grade of cytodamaging effect of mastitis. Of the other markers,
      ATR and Cl- proved to be more adequate for the differentiation than BSA. It can
      be concluded that, in addition to SCC, first of all NAGase can be recommended for
      use as an inflammatory parameter in pharmacodynamic studies. Besides these two
      parameters, ATR and Cl- can also be chosen as a possible third marker.

PMID- 9557319
TI  - Comparison of the protein patterns of Erysipelothrix rhusiopathiae strains by SDS
      PAGE and autoradiography.
AB  - The proteins of 12 Erysipelothrix rhusiopathiae strains were radiolabelled with L
      [35S] methionine, and the protein fractions were detected by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. The
      strains were found to differ from each other in their protein patterns; thus, it
      was concluded that the method applied could provide useful data for the
      identification of strains. The described procedure was used for determining the
      percentage contents of protein fractions of identical molecular mass within the
      strains compared. The results show that there is no significant correlation
      between the type of the strains and the percentage of identical molecular weight
      fractions.

PMID- 9557320
TI  - Extrapiscine development of Myxobolus drjagini Akhmerov, 1954 (Myxosporea:
      Myxobolidae) in oligochaete alternative hosts.
AB  - The extrapiscine development of Myxobolus drjagini, a myxosporean parasite of the
      head, operculum and buccal cavity of the silver carp (Hypophthalmichthys
      molitrix), was studied in experimentally infected oligochaetes, Tubifex tubifex.
      After infection of uninfected tubificids with mature spores of M. drajagini,
      development of actinosporean stages was first observed by light microscopy 27
      days after infection. Triactinomyxon stages of M. drjagini emerged from the worms
      after 91 days of intraoligochaete development. In histological sections, early
      pansporocysts were found in the gut epithelium of the experimental oligochaetes
      42 days after infection. Mature pansporocysts, each containing 8 triactinomyxons,
      appeared 79 days after infection. After rupture of the epithelial cell and the
      pansporocyst, free actinosporean stages were found in the gut lumen of the
      oligochaete. Actinosporean stages released from oligochaetes appeared in the
      water 91 days after infection. They were floating in the water and showed a
      typical triactinomyxon form. Each triactinomyxon had three pyriform polar
      capsules, a sporoplasm with 14 secondary cells inside the spore body, a
      moderately long style and slightly bent, trifurcated, conically ending tails. The
      total length of the triactinomyxon measured approximately 198 microns. The
      prevalence of infection in 51 oligochaetes proved to be 9.8%. No infection was
      found in the control oligochaetes.

PMID- 9557321
TI  - Attempts to analyse Anguillicola crassus infection and the humoral host response
      in eels (Anguilla anguilla) of Lake Balaton, Hungary.
AB  - Since the introduction of Anguillicola crassus into Europe, anguillicolosis has
      been a considerable problem in several countries. From 1991, periodical eel
      mortality occurred in Lake Balaton, Hungary. However, eels with a worm burden of
      20 to 50 parasites did not show severe swimbladder lesions, which observation
      cast doubts on the primary aetiological role of the parasite in the eel kill. In
      order to study the pathology of the infection, from the spring of 1996 until
      October of the same year, 51 eels were collected from two regions of Lake Balaton
      and examined for swimbladder changes. To detect humoral antibodies, an enzyme
      linked immunosorbent assay (ELISA) was performed, using cuticular-oesophageal
      worm antigen. The results of the test show the applicability of the method.
      However, no direct correlation was found between antibody levels or the intensity
      of infection and the swimbladder lesions. The low level of specific antibodies
      and the increasing severity of swimbladder changes in the autumn suggest that
      parasite-induced immunity is insufficient to prevent reinfection.

PMID- 9557322
TI  - Effects of vitamin E and selenium on some rumen parameters in lambs.
AB  - The effects of supplemented selenium and vitamin E on a number of rumen
      parameters such as the population of rumen protozoa, pH, concentration of
      volatile fatty acids and ammonia nitrogen in the rumen content were studied.
      Eight lambs were randomly allocated into two groups: a control group and an
      experimental group receiving vitamin E (DL-alpha-tocopheryl acetate, 250 mg/kg of
      feed) and selenium (sodium selenite, 0.3 mg/kg of feed) supplementation. Samples
      of rumen content were taken from all lambs three times daily once a week (before
      feeding as well as 3 and 6 h after feeding) over a period of 10 consecutive
      weeks. In addition, the lambs were weighed at the end of experiment. The total
      counts and percentage proportions of rumen protozoa, the pH value, and the levels
      of ammonia nitrogen and volatile fatty acids were determined in the samples of
      rumen content. The levels of acetic acid, propionic acid, butyric acid and total
      volatile fatty acids, the total counts of protozoa, and the percentage proportion
      of Diplodinium were found to be significantly higher in the supplemented than in
      the control group (P < 0.05, P < 0.01), whereas the pH values and the percentage
      proportion of Dasytricha ruminantium were significantly lower in the supplemented
      group than in the control (P < 0.05). However, there was no statistically
      significant difference between the two groups in ammonia nitrogen levels. The
      body mass gain of lambs in the supplemented group was significantly higher than
      that of the control animals (P < 0.01). Combined selenium and vitamin E
      supplementation of the lambs' ration caused an increase in the levels of volatile
      fatty acids, total counts of protozoa, and body mass gain while decreasing the pH
      value of the rumen content.

PMID- 9557323
TI  - Zoonoses in the meat industry: a review.
AB  - Zoonoses are diseases, the infections of which can be transmitted between man and
      animals. Only a few are of importance with respect to poultry meat and meat from
      cattle, sheep, horses and goats. Advances in the control of diseases such as
      tuberculosis, brucellosis and trichinosis in animals have reduced the hazards
      posed to workers in the meat industry and to consumers of meat. However,
      inspection of animals ante- and post-mortem cannot detect all infectious agents
      present. This applies particularly to bacteria such as Campylobacter, Salmonella,
      verotoxigenic and other pathogenic Escherichia coli and Yersinia. Protection of
      meat workers from infection depends upon taking normal hygienic precautions,
      which also protect the meat from contamination from the workers. Consumers are
      exposed to a smaller range of zoonoses than meat workers because they encounter
      only meat that has passed inspection. In addition, heavily contaminated parts of
      the animal, such as the hide, feathers and viscera have been removed. Further
      advances in making meat safer are likely to result from the introduction of
      Integrated Quality Assurance systems. These involve identifying, monitoring and
      keeping records of the disease status and treatment of each animal (or poultry
      flock) so that its history is known when it reaches the abattoir. They should
      also include programmes aimed at minimising colonisation by zoonotic bacteria
      such as camplyobacters, salmonellas and verotoxigenic Escherichia coli.

PMID- 9557324
TI  - The subchondral bone plate.
AB  - Pauwels (1965) and subsequent workers in the same field have shown that the
      distribution of the subchondral density within a joint surface can serve as a
      parametric measurement which reflects the main stress acting on a joint. Our own
      investigations on anatomical specimens have demonstrated that this subchondral
      mineralization does indeed show regular distribution patterns from which
      conclusions about the mechanical situation within an individual joint may be
      drawn. Since radiographical densitometry and histological methods are only
      available for determining the adaptive reaction of the bone to the particular
      mechanical situation in a joint after death, the information obtained applies
      only to an end situation and tells us nothing about the development of the
      changes with time. Furthermore, investigations carried out on human specimens by
      radiographical densitometry mostly apply to samples of a particular age, since
      such specimens can be acquired only from departments of pathology, forensic
      medicine or anatomy. The functional reactions of the bone tissue to repeated long
      term changes in the loading--lengthy immobilization and subsequent
      remobilization, for instance, or heavy loading over a considerable period of time
      -cannot be followed by any ordinary method in experimental animals, since the
      death of the animal is a prerequisite for the precise quantitative examination of
      the bone tissue. This applies also to attempts to follow the process by means of
      animal experiments. CT OAM has been developed as a method which, based on CT, can
      provide a surface representation of the 3-D density distribution in the joints of
      living subjects. Comparative studies were carried out to establish and confirm
      the validity of the procedure. These have shown (1) that the results obtained
      from anatomical specimens are identical with those obtained in the living; (2)
      that secondary CT sections are suitable for evaluation and that the spectrum of
      joint surfaces examined can be extended to include the whole joint (if this were
      not so, effects caused by the apparatus--particularly the partial-volume effect-
      would render the procedure impossible); and finally (3) that the distribution of
      the Hounsfield density within the subchondral bone represents the distribution of
      the mineralization. The mineralization patterns found by us in different joints
      of normal subjects have shown that these patterns can be brought into line with
      current models of joint mechanics. The radiocarpal joint, for instance, has
      revealed the various types of loading occurring within physiological limits.
      Information has also been obtained about the age-related changes taking place in
      the hip, wrist and ankle joints. The increase of the total mineralization in
      gymnasts can be related to the qualitative and quantitative adaptation to an
      increased peak loading, and reduced mineralization to a lengthy reduction in use
      during, for instance, postoperative immobilization. In groups of patients with
      various diseases of mechanical origin (shoulder instability, malalignment of the
      main axis, defective repositioning of healed fractures, rupture of the rotator
      cuff, meniscectomy or rupture of the anterior cruciate ligament), a pattern of
      mineralization is found which is different from the normal picture. These
      findings reflect the abnormal mechanical situation. The mineralization pattern of
      the femoropatellar joint has revealed the differing etiologies of medial and
      lateral cartilage damage and the examination of patients with lunatomalacia has
      made it possible to recognize a genetic disposition. The postoperative comparison
      of the mineralization patterns of patients with genu varum who have undergone a
      correction osteotomy and the results of animal experiments on various procedures
      for reconstructing the anterior cruciate ligament or a primary replacement of the
      meniscus, have produced results which make it possible to judge the success or
      failure of the operation. (ABSTRACT TRUNCATED)

PMID- 9557325
TI  - HIV/AIDS and deafness.

PMID- 9557326
TI  - Emerging from our isolation.

PMID- 9557327
TI  - How do deaf and hearing mothers regain eye contact when their infants look away?
AB  - The authors examine the effects that results when 9-month-old deaf and hearing
      infants break eye contact during face-to-face interactions with their deaf or
      hearing mothers. Of particular interest are mothers' responses when their infant
      looks away, and mothers' degree of success at regaining visual attention by using
      active bids in either the tactile, visual, or auditory modes. The authors also
      examine instances of maternal observing and waiting for the infant to reinitiate
      visual contact. For deaf infants, visual and tactile modalities are particularly
      important for communicating, interacting, and gaining information about their
      environment. While hearing parents have been shown to compensate intuitively for
      a deaf child's inability to perceive auditory cues (Koester, 1992, 1995), deaf
      parents may offer important insights into the use of other modalities to elicit
      and maintain a deaf infant's attention. Results of the study indicate a greater
      reliance among deaf mothers on visual strategies to regain infant attention, and
      a greater emphasis on vocalizations by hearing mothers, regardless of infant
      hearing status.

PMID- 9557328
TI  - Assessing substance abuse problems in deaf and hard of hearing individuals.
AB  - Professionals who provide services to deaf and hard of hearing individuals may
      encounter situations related to abuse of alcohol and other drugs. Getting access
      to an agency that can provide an appropriate chemical dependency assessment for a
      deaf or hard of hearing person is difficult because there are no formalized
      assessment tools normed or specifically designed to use with such individuals.
      Additionally, most assessors are unfamiliar with how to work with deaf and hard
      of hearing people, less likely to be fluent in American Sign Language, and
      unaware of appropriate treatment options. The present article provides an
      overview of chemical dependency, assessment issues, and considerations unique to
      the deaf and hard of hearing population. A chemical dependency assessment tool
      developed by the Minnesota Chemical Dependency Program for Deaf and Hard of
      Hearing Individuals is described, as well as a case study that illustrates
      application of the assessment process.

PMID- 9557329
TI  - Mathematics reform in the education of deaf and hard of hearing students.
AB  - In response to increased demand for competent workers who possess skills in
      problem solving, cooperative work, and technology, education professionals have
      set out to reform mathematics education. The purpose of the present study was to
      determine the state of mathematics reform in the education of deaf and hard of
      hearing students. A national survey was sent to administrators and faculty at
      schools for the Deaf seeking information on mathematics programs and instruction.
      Data were analyzed by profession (i.e., administrator, teacher) and grade level
      (K-4, 5-8, 9-12). Results show that some aspects of reform (e.g., problem
      solving, use of concrete materials) have been incorporated into the deaf
      education mathematics curriculum but that many 'traditional' techniques (e.g.,
      drill and practice, rote memorization) remain in use. Data support the need for
      increased attention to mathematics education reform within deaf education.
      Recommendations are provided to professionals in the field to better prepare
      students for the 21st century.

PMID- 9557330
TI  - The Deaf Mentor Experimental Project for young children who are deaf and their
      families.
AB  - The Deaf Mentor Experimental Project investigated the efficacy of deaf mentor
      services to young deaf children and their families. These services focused on
      deaf adults (mentors), who made regular home visits to the children and their
      families; shared their language (American Sign Language), culture, and personal
      knowledge of deafness with the families; and served as role models for the
      children. The children also received regular home visits from a hearing parent
      adviser who helped the family promote the child's early listening, English, and
      literacy skills. The result was a bilingual-bicultural home environment for these
      children. The children who received deaf mentor services were compared to matched
      children who did not receive these services but who received parent adviser
      services. Children receiving this early bilingual-bicultural programming made
      greater language gains during treatment time, had considerably larger
      vocabularies, and scored higher on measures of communication, language, and
      English syntax than the matched children.

PMID- 9557331
TI  - A comparison study of educational involvement of hearing parents of deaf and
      hearing children of elementary school age.
AB  - This study was conducted to determine if a difference exists in level of
      educational involvement between hearing parents of deaf children and hearing
      parents of hearing children. Participating parents were asked to complete a 23
      question survey about their involvement in their children's education over the
      past year. Neither group of parents demonstrated a significantly higher level of
      involvement in their children's education. However, parents of deaf children
      observed their children in the classroom more than parents of hearing children;
      parents of hearing children volunteered in their child's classroom more than
      parents of deaf children.

PMID- 9557332
TI  - National survey of school counselors working with deaf and hard of hearing
      children. Two decades later.
AB  - The first national survey of school counselors for deaf children was conducted by
      Marie Curtis in 1975. She found that deaf students needed counseling services and
      that existing services were poor to fair in meeting these students' needs. The
      purpose of the present study was to follow up on Curtis's study by seeking
      current information on the demography of school counselors as well as the present
      roles and skills of counselors working with deaf children. Survey respondents
      indicated that they spent most of their time providing individual and group
      counseling. A large majority of respondents said their communication skills with
      students were adequate or better. The three most frequently identified student
      problems seen were "problems with peer relations," "difficulty with decision
      making." and "poor self-esteem." Comparisons between the present study and the
      Curtis study indicate that counselor competence has improved in the intervening
      years. Specifically, survey respondents in the present study gave themselves much
      higher ratings in the areas of communication skills, training, and counseling
      skills.

PMID- 9557333
TI  - Profiling Hispanic deaf students. A first step toward solving the greater
      problems.
AB  - As the number of Hispanic individuals in the United States increases, so does the
      number of Hispanic hearing impaired children. This trend gives cause for concern
      within current educational systems because research suggests that Hispanic
      hearing impaired students demonstrate a lower rate of scholastic success than
      hearing and deaf peers (Bennett, 1988). One step toward solving this problem is
      to reexamine educational and assessment techniques employed with this diverse
      population. A logical first stage would include construction of demographic
      "profiles" or descriptions of student populations. The present study provides
      such information and identifies the unique characteristics of Hispanic students
      at the Texas School for the Deaf. The author discusses trilingual
      (ASL/English/Spanish) situations and problems related to multilingual home and
      school environments. A model is proposed for language instruction and support
      services programs.

PMID- 9557334
TI  - The association between racelessness and achievement among African American deaf
      adolescents.
AB  - Generally, deaf students do not achieve as well academically as their hearing
      peers. Within the deaf population, African American deaf students achieve less
      well academically than their White peers. There are, of course, both deaf and
      hearing African American students who excel in school. What then, are the factors
      that contribute to the accomplishments of successful African American deaf
      students in school? The present study explored the relationship of the construct
      of racelessness to school success among African American deaf adolescents. Data
      were collected on 32 deaf adolescents from six public schools. There was little
      support for racelessness as a robust construct in the present study. Although
      exceptions existed, there was no significant relationship between racelessness
      and achievement.

PMID- 9557335
TI  - [Some personal comments on the care given to patients with benign prostatic
      hypertrophy in the primary care environment].

PMID- 9557336
TI  - [The Urinary Tract Diseases Dispensary and Clinic of the Instituto Rubio (1885).
      1st hospital service specializing in urologic pathology in the history of Spanish
      medicine. 1st period. The Instituto Rubio in Hospital de la Princesa (1880
      1896).(I)].
AB  - In May 1880, a royal decree signed by the Minister of the Interior, F. Romero
      Robledo, created the Institute of Operative Therapy under the gratuitous
      direction of Dr. Federico Rubio y Gali. Although it was located at the Hospital
      de la Princesa of Madrid, it was not dependent on the Institutions of Charity.
      According to the royal decree, major surgical procedures and specialized
      operative techniques would be performed at this Institute. Thus, the first
      teaching hospital was created in Spain, with operating rooms, dispensaries and
      polyclinics dedicated primarily to surgical specialties which were established at
      the Institute after 1880. The Institute's section for Diseases of the Urinary
      Tract, created in October 1885, was entrusted to the Madrid citizen Enrique
      Suender Rodriguez (1829-1897), the leading specialist in urology in our country
      at that time (his 100th death anniversary was commemorated last year) and whose
      assistant was Luis Gonzalez Bravo y Serrano.

PMID- 9557337
TI  - [The Urinary Tract Diseases Dispensary and Clinic of the Instituto Rubio (1885).
      !st hospital service specializing in urologic pathology in the history of Spanish
      medicine. 2nd period. The Instituto Rubio in Moncloa (1896-1936).(II)].
AB  - In 1896, for different reasons and requirements, the Institute of Operative
      Therapy of the Hospital de la Princesa was transferred to a new and ample site in
      the Moncloa district in Madrid, with building complexes and pavillions for the
      dispensaries and policlinics for practically all surgical specialties, with all
      the necessary equipment. This came to be known as the "Rubio Institute". Luis
      Gonzalez Bravo y Serrano, Suender's assistant, was in charge of the new
      Dispensary and Clinic for Diseases of the Urinary Tract of the Institute until
      1929; Carlos Negrete de los Reyes was his assistant. Both specialists' initiative
      and drive led to the creation of the Spanish Urological Society in 1911. They
      were elected President and Secretary, respectively, to the first Board of the
      Society. This article reviews the activities of the specialists in Diseases of
      the Urinary Tract of the new Institute in the provision of care, in the field of
      teaching and research, from their brilliant beginnings to their decline in 1936,
      when the Spanish Civil War broke out. In my view, for all the contributions of
      those who worked in this Section and its significant influence on the Spanish
      specialists during its existence of more than 50 years, the Dispensary and Clinic
      of Diseases of the Urinary Tract of the Rubio Institute should be considered the
      catalyst and essence of Spanish urology and the Spanish Urological Society.

PMID- 9557338
TI  - [Transurethral resection in the treatment of benign prostatic hypertrophy:
      analysis of its results].
AB  - OBJECTIVE: To analyze the results achieved with transurethral resection in the
      treatment of benign prostatic hyperplasia. METHODS: We analyzed the results
      achieved with transurethral resection in 400 patients with benign prostatic
      hyperplasia who had been treated at the Joaquin Albarran teaching hospital. The
      procedure was utilized for prostates weighing up to 50 gm and middle lobe
      involvement independent of its size. Sterile water was used as irrigant since it
      permits excellent vision, it is low-cost and carries a low risk of complications
      associated with intraoperative osmotic diuresis. RESULTS: 4.75% of the cases
      required blood transfusion (not more than two units). The intraoperative
      complication rate was 2.75%; hemorrhage (2%), capsular perforation (0.5%), and
      one death from myocardial infarction (0.25%). Hematuria resolved within 48 h
      postoperatively in 83.75% and the urethral catheter was removed in 82.75% within
      the first 72 h. Urinary tract infection was the most common postoperative
      complication; 8.5% were acute and 3.25% presented late. Urethral stenosis was
      observed in 2.25% and sclerosis of the neck was observed in 1.75%. Good results
      were achieved in 360 patients (90%). The mean length of hospital stay was 3.8
      days. There were two deaths (0.5%); both were due to myocardial infarction.
      CONCLUSIONS: Transurethral resection in the treatment of benign prostatic
      hyperplasia achieved good results in 90% of our patients. The length of hospital
      stay was short and the mortality rate was low.

PMID- 9557339
TI  - [Renal carcinoma with tumor thrombus in the vena cava and auricle. Experience and
      review].
AB  - OBJECTIVES: To report on our experience in the treatment of renal cell carcinoma
      with vena caval or right atrial extension, with special reference to the level of
      involvement and the surgical technique indicated for each case. METHODS: From
      early 1975 to April, 1997, 212 patients underwent surgery for renal cell
      carcinoma. Of these, 15 patients (11 male, 4 female), aged 27 to 73 years, had a
      tumor thrombus extending to the inferior vena cava. The tumor was located in the
      right kidney in 11 patients and in the left kidney in 4 patients. The tumor
      thrombus was infrahepatic in 10 cases, it extended beyond the suprahepatic veins
      in 3 cases, and 2 cases showed right atrial extension. The 10 patients with
      infrahepatic caval thrombus underwent radical nephrectomy with cavotomy and
      thrombus removal. In the remaining 5 patients with suprahepatic or atrial
      extension, thrombus removal was performed via cardiopulmonary by-pass with
      hypothermic circulatory arrest, with the assistance of a team of cardiac
      surgeons. RESULTS: Pathological staging showed 2 T3cNoMo, 1 T3bNoMo and 2 T3bN1Mo
      in the patients who underwent cardiopulmonary bypass. There were 5 T3bNoMo, 2
      T3bN2Mo, 1 T3bN2M1, 1 T4NoMo and 1 T4N1M1 in the group of patients with
      infrahepatic thrombus. There were two postoperative deaths. The overall survival
      rate was poor. Six patients are alive at 3-26 months' follow-up and 9 have died
      from disease progression. Patients with lymph node involvement or metastasis at
      the time of diagnosis had a worse survival rate. CONCLUSIONS: Surgical treatment
      of renal cancer with vena caval extension is specially difficult depending on the
      level of involvement, which must therefore be determined with precision. MRI is
      an effective and noninvasive technique. Tumors with thrombus below the
      suprahepatic veins can be managed by the direct approach with cavotomy. The use
      of cardiopulmonary bypass is advocated for tumors with suprahepatic caval or
      atrial extension. Tumors with caval-atrial extension have a negative influence on
      survival.

PMID- 9557340
TI  - [Characterization of the DURR (dynamic urethral resistance relation] in the study
      of function lower urinary tract symptoms in the male].
AB  - OBJECTIVES: To determine the type and to quantify the DURR phenomena in the male.
      METHODS: We conducted a clinical and urodynamic study in 31 male patients with
      functional lower urinary tract symptoms. RESULTS: DURR is produced by two types
      of mechanisms: urethral rigidity and contraction of the urethral wall. The
      patients with DURR produced by rigidity showed a higher score for irritative
      urinary symptoms. The patient with DURR produced by the contraction of the
      urethral wall had greater urodynamic consequences (increased opening pressure and
      PURR curve). The obstructive urinary symptoms were more intense when the DURR
      presented in the second phase of voiding (after reaching the maximum flow).
      CONCLUSIONS: The DURR phenomena have clinical and urodynamic consequences in
      males with functional lower urinary tract symptoms; therefore their type and
      quantity should be adequately determined.

PMID- 9557341
TI  - [Occlusive urethral systems: can they constitute an alternative in the management
      of female stress incontinence?].
AB  - OBJECTIVE: To determine the utility of the urethral plug in the management of
      female stress urinary incontinence. METHODS: A prospective clinical study was
      conducted in 20 female patients with stress urinary incontinence in order to
      evaluate the efficacy of a new urethral plug. The mean age was 59.6 +/- 6.2 years
      (range 40-66). The study design included 3 visits (4 weeks). The results were
      considered "positive" when urinary incontinence decreased and the patient
      referred a subjective sensation of improvement, and "negative" if otherwise.
      RESULTS: Positive results were demonstrated in 8 patients (40%). Ten patients
      (50%) refused to continue, mainly due to urinary tract infection in 7 cases
      (35%), difficulties in plug use (loss of plugs, anomalous urethral anatomy,
      cystocele,...) in 6 cases (30%) and urethral mucosa irritation in one case (5%).
      No plug migrated into the bladder. The initial urinary incontinence grade in the
      positive cases were: minor in 4 (50%), mild in 2 (25%) and severe in 2 (25%). We
      found no statistical relationship between the urinary incontinence grade and
      clinical results. The patients used a median of 5 plugs per day. Of the 10
      patients who completed the study, 5 (50%) refused to continue using the plug and
      5 (50%) decided to continue using the plug in combination with electrostimulation
      and/or pelvic floor exercises. CONCLUSIONS: The use of the urethral plug in the
      management of female stress urinary incontinence is not an alternative to
      surgical treatment or pelvic floor rehabilitation. However, it could be useful
      for patients who are unwilling or unfit for surgery. Finally, the urethral plug
      is an alternative to the use of collecting systems or devices in female stress
      urinary incontinence.

PMID- 9557342
TI  - [Metanephric renal adenoma].
AB  - OBJECTIVE: To describe a case of metanephric adenoma, a rare and little known
      tumor with no potential to malignancy. This tumor type can occasionally coexist
      with Wilms' tumor, with which it is histogenically related. METHODS/RESULTS: A 54
      year-old female patient was referred to the Urology Service for a small mass in
      the left kidney that had been incidentally detected during an ultrasound
      evaluation. Patient evaluation disclosed a solid, circumscribed, unencapsulated
      mass of 2.3 cm in its largest segment. It was mainly localized in the medulla of
      the kidney, although it was extensively in contact with the renal cortex.
      Histologically, it was comprised of small epithelial cells in a tubular or
      papillary arrangement, without atypia, mitosis, necrosis or invasion of adjacent
      renal parenchyma or vascular structures, and with abundant psammoma-like
      calcifications. The histological findings were characteristic of metanephric
      adenoma. CONCLUSION: Metanephric adenoma is an uncommon, morphologically distinct
      tumor type, with characteristic histopathological features. Despite its size, it
      is benign and should be distinguished from renal cell carcinoma or Wilms' tumor.

PMID- 9557343
TI  - [Abscessed primary retroperitoneal leiomyoma].
AB  - OBJECTIVE: To describe a case of primary retroperitoneal leiomyoma presenting as
      pelvic abscess. METHODS/RESULTS: A patient who had consulted for fever and
      hypogastric and perineal pain is described. The diagnostic imaging techniques
      disclosed a heterogeneous pelvic mass compatible with an abscess, which was
      drained. After the purulent material had been drained, the mass was removed
      surgically. The pathological analysis of the surgical specimen disclosed a
      retroperitoneal leiomyoma. CONCLUSION: An abscessed primary retroperitoneal
      leiomyoma is a very uncommon tumor.

PMID- 9557344
TI  - [Paratesticular adenomatoid tumor, presentation as epididymal pain].
AB  - OBJECTIVE: To describe an additional case of adenomatoid tumor of the epididymis.
      METHODS/RESULTS: A 55-year-old man consulted for epididymal pain. Palpation and
      ultrasound evaluation disclosed an epididymal tumor. The patient underwent
      orchidectomy; histological examination of the surgical specimen confirmed an
      adenomatoid tumor. CONCLUSIONS: Adenomatoid tumor of the epididymis is an
      uncommon tumor of the paratesticular tissue. Although its etiopathogenesis
      remains unclear, there appears to be a mesothelial involvement. Ultrasound
      evaluation and clinical examination are essential in making the preoperative
      diagnosis. It is a benign tumor and surgical excision can achieve cure. If the
      intraoperative frozen section is found to be benign, the tumor can be excised or
      enucleated without semicastration.

PMID- 9557345
TI  - [A rare type of neoplasia. Report of 2 cases].
AB  - OBJECTIVE: To report two additional cases of carcinosarcoma of the bladder and
      review the literature. METHODS/RESULTS: Two cases of bladder tumor are described.
      Both patients were male whose median age at diagnosis was 69.5 years. They had
      consulted for post-void hypogastric pain and hematuria. A diagnosis of bladder
      tumor was made on the basis of the radiological and ultrasound findings and a
      partial cystectomy was performed. Histological examination with
      immunohistochemical techniques revealed carcinosarcoma of the bladder.
      CONCLUSIONS: Carcinosarcoma is a mixed tumor with a high grade of malignancy and
      is rarely located in the bladder. Its clinical presentation is not unlike that of
      other bladder tumors. Diagnosis is always by histology using immunological
      techniques. It has a very poor prognosis. Because it is a rare tumor type, its
      natural history is unknown and treatment remains unclear, although radical
      surgery continues to be the most widely utilized.

PMID- 9557346
TI  - [Systemic lupus erythematosus and pyeloureteral obstruction. Description of a
      case].
AB  - OBJECTIVE: To discuss the clinical implications of systemic lupus erythematosus
      (SLE) as a complication of a urological condition. METHODS: Herein we describe a
      patient who presented with acute pyelonephritis due to ureteropelvic juntion
      stenosis, and a superimposed activation of SLE that had not been previously
      detected. RESULTS: This form of presentation led to a delay in making the
      diagnosis since it was focused urologically. The diagnosis of SLE was based on
      the clinical features, determination of antinuclear antibodies (ANA) and a
      decrease in serum complement. CONCLUSION: When a patient consults with fever
      arising from a urological condition that is refractory to conventional therapy,
      it is mandatory to make the differential diagnosis from other disease entities,
      as shown in this case.

PMID- 9557347
TI  - [Basaloid prostatic proliferations].

PMID- 9557348
TI  - A giant left renal cyst presenting as obesity: a unique presentation.
AB  - OBJECTIVE: Benign renal cysts are commonly found in adult patients. However,
      giant renal cysts measuring more than 15 cm in greatest diameter or containing
      more than 1500 cc of fluid are rarely seen. A giant renal cyst presenting as
      obesity, a unique form of presentation, is described herein. METHODS/RESULTS: We
      report the unique case of 78-year-old male who was diagnosed with a 25 cm left
      renal cyst after presenting solely with diffuse progressive abdominal distention.
      He had no other signs or symptoms and had been followed at our institution for
      seven years with a diagnosis of obesity. The patient was effectively treated by
      open renal cyst decortication. CONCLUSIONS: Giant renal cyst measuring > or = 15
      cm or containing more than 1500 cc of fluid rarely occur. This case is unique in
      that unlike other adult patients, this patient presented with no sign or symptom
      other than diffuse, nonlateralizing, abdominal distension.

PMID- 9557349
TI  - [Financing health].

PMID- 9557350
TI  - [Quality of prescription at an on-demand clinic: a preliminary examination].
AB  - OBJECTIVES: To analyse the qualitative composition of medication prescribed to
      paediatric patients, in function of the intrinsic value of the medication and
      active principles used, and to evaluate risks run by children through being
      exposed to medication. DESIGN: An observational, descriptive, crossover study.
      SETTING: Paediatrics service of Puerto de la Torre Health Centre (Malaga);
      serving a fundamentally urban population, with rural areas round about.
      PARTICIPANTS: All the patients seen during two consecutive weeks of November
      1994. 15 cases of the 457 seen were excluded. The unit of analysis was a visit.
      MAIN MEASUREMENTS: Age, reason for consultation and medication prescribed at each
      attendance were recorded. Four age groups were defined: A (0-12 months), B (12-36
      months), C (36-60 months) and D (> 60 months). On the basis of the initial
      records, the following quantitative variables per visit were broken down: number
      of drugs; number of drugs with high intrinsic value (HIV); number of drugs with
      low intrinsic value (LIV); number of active principles; number of HIV active
      principles; and number of LIV active principles. RESULTS AND CONCLUSIONS: The
      incidence of medical prescription in the attendance sample was 85.1%. It was
      highest in group C and lowest in group A. Average medication per attendance was
      1.36 +/- 0.08. Group C was identified as the group with the highest average of
      drugs prescription, HIV drugs, active.

PMID- 9557351
TI  - [Diagnosing community health by factorial analysis].
AB  - OBJECTIVE: To identify the needs of medical care and to determine priorities in
      the delivery of health services by the factorial analysis of the health
      indicators obtained from study of the demographic, economic and family features
      of those registered at a Primary Care Centre. DESIGN: Descriptive and crossover.
      SETTING: Tlalpan area, Federal District, Mexico, divided into geo-statistical
      zones. Patients and other participants. A randomised sample of 590 dwellings,
      with proportional coverage, based on 173,000 inhabitants and 17,895 ordinary
      dwellings. INTERVENTION: Survey conducted in the home (April-July, 1993).
      MEASUREMENTS AND MAIN RESULTS: 16 health markers were classified into four
      categories, demographic, social, health-damaging and family. Nine markers with a
      reading on the Pearson's correlation index over 0.40 were chosen. Factorial
      analysis determined two main factors. CONCLUSIONS: The identification of the main
      risk factors by means of factorial analysis helped in diagnosing community
      health. A project needs to be worked out to define a methodology for studying
      medically dysfunctional families and to introduce a prevention and early
      diagnosis programme for Diabetes Mellitus.

PMID- 9557352
TI  - [Validation of an instrument for identifying styles of the professional practice
      of the primary care doctor].
AB  - OBJECTIVE: To elaborate and validate a questionnaire for identifying common
      styles of Primary Care doctors' practice. SETTING: Primary Health Care. Public
      sector in Spain. DESIGN: This was a study to validate a questionnaire
      administered in two phases with different samples. In the first phase, the items
      (item-total correlation, using Alpha on eliminating item), validity of
      construction, empirical validity and internal consistency, were analysed. In the
      second, discriminatory validity and reliability of the questionnaire (test
      retest) were calculated. MEASUREMENTS AND MAIN RESULTS: 81.5% of the doctors
      replied in the first phase; and 100% in the second. Two factors were isolated
      with the Principal Components procedure, which confirmed the validity of the
      questionnaire's construction (52% variance explained). Internal consistency
      (Alphas ranged between 0.55 and 0.75) and reliability (ranging between 0.50 and
      0.95 in function of the time elapsed) were also demonstrated. CONCLUSIONS: This
      instrument could be used to differentiate two styles in practice, characterised
      by focusing on the physical illness vs the psycho-social aspects of the disease
      process. The instrument is also useful because it gives the feeling of control
      over the task.

PMID- 9557353
TI  - [The special training month for tutors and residents in family medicine in
      Valencia: evaluation of 3 cases].
AB  - OBJECTIVE: To evaluate the activity in the special training month (STM) for
      tutors and residents in Family Medicine in Valencia between 1994 and 1996.
      DESIGN: Descriptive and longitudinal. SETTING: Thirteen teaching health centres.
      PARTICIPANTS: 48 tutors and 102 residents. MEASUREMENTS AND MAIN RESULTS:
      Requests from tutors for clinical recycling, research and other activities.
      Evaluations of hospital staff, tutors and residents. 41.6% of tutors did their
      STM in three years, 29.2% in 2 years and 29.2% in one. Of the 105 evaluations
      sent in, 92 (87.6%) were for clinical recycling, 9 (8.6%) research and 4 (3.8%)
      other activities. The most visited specialities were Dermatology, Cardiology,
      Radiology and Rheumatology. Staff evaluated as very good the interest shown and
      punctuality; between good and very good, their knowledge and skills, with
      commentaries in 36% of evaluations on improvement of coordination between levels.
      64.4% of tutors considered the STM very favourably, reflected in nine
      commentaries that the activity was motivating and in six that it promoted
      relationships between the Primary and Specialist care levels; and that it had an
      objective repercussion on teaching through 44 clinical sessions reported during
      1996. Improvements were proposed in the organisation of teaching activities. 49%
      of residents were assigned a set tutor. CONCLUSIONS: The STM is valued positively
      by tutors, residents and staff.

PMID- 9557354
TI  - [Relationship between anxiety and family dynamics].
AB  - OBJECTIVE: In the present study we tried to find the likely association between
      anxiety and a disturbed family dynamic in patients who attended Primary Care for
      consultation. DESIGN: An observational, crossover study with 150 patients (64.7%
      women) chosen by systematised random sampling was performed. Patients were
      grouped in various bivariable categories: sex, marital status, where from,
      cultural level, occupation, size of family, stage of their life-cycle, family sub
      system and income, which were compared with the results from the Stai Anxiety and
      the Apgar Family tests. 95% significance level; two months data-gathering.
      RESULTS: Among the most relevant findings were negative correlation in the value
      of the Stai Anxiety test vs the Apgar Family test, with r = -0.27 and level of
      significance between [-0.42 < r < -0.12]. A multivariant study using Dummy type
      variables found association between Anxiety and being Female, with a Beta
      coefficient of -6.2172 [CI -10.2044/-2.0342]. There was also association of size
      of family and disturbed family dynamic, with Beta coeff. = -0.2437 and CI [
      0.4706/-0.0168]. CONCLUSIONS: a) There is a correlation between anxiety and
      disturbed family dynamic. b) Being female is a risk factor, when before anxious
      patients, of a disturbed family dynamic. c) Family size is also a risk factor,
      before an anxious patient, of a disturbed family dynamic.

PMID- 9557355
TI  - [A retrospective evaluation of the behaviour of groups under out-patient care at
      a health center].
AB  - OBJECTIVES: To study and analyse the Out-Patient Care Groups (OCGs), and evaluate
      how they affect use of health resources. DESIGN: An observational, retrospective
      study. SETTING: Ciudad Jardin Health Centre, Malaga. PARTICIPANTS: 2999 patients
      with a clinical history opened before 31.12.95, chosen from 5 of the 17 medical
      lists at the Health Centre, were included. RESULTS: The statistical analysis was
      performed with the SPSS software package of the Calculation Centre at Malaga
      University. A descriptive test produced the following results: 33% of the
      patients were classified in OCG 41 (combination of 2 or 3 out-patient diagnosis
      groups in people over 34); 19% belonged to groups of stable or unstable chronic
      illnesses (OCGs 8, 9 and 10); and 9% had acute children's diseases. Then multiple
      regression constructed a model with the OCGs as independent variable and annual
      visits, further tests performed and referral to specialists as dependent
      variables. In this model the OCGs were able to explain 20.3% of resource
      consumption. CONCLUSIONS: In the retrospective study and with a limited sample of
      2999 patients, the OCGs are able to explain 20.3% of resource consumption.
      However, it does seem a valid model for discriminating between normal and over
      using patients.

PMID- 9557356
TI  - [Do the complaints of primary care users vary with the care model?].
AB  - OBJECTIVES: 1. To compare the traditional model (TM) and Primary Care teams
      (PCTs) on the index of complaints. 2. To determine whether the reasons for
      complaints vary with the care model. DESIGN: An observational, cross-sectional
      study. SETTING: Primary Care Area 4, INSALUD, Madrid, covering 526,987
      inhabitants. PARTICIPANTS: The complaints presented at PC Centres during 1993
      were included. Those presented for reasons not concerning the centre were
      excluded. In all, 448 complaints were studied. MEASUREMENTS AND MAIN RESULTS:
      Significant differences were found in the general index of complaints according
      to the care model. Statistically significant differences were detected between
      PCT and the TM for complaints due to disagreement with the treatment and
      disagreement with the follow-up procedures. CONCLUSIONS: Since the indicators of
      prescription profiles and the following of procedures are better in PCTs than in
      the TM, perhaps patients should be encouraged to participate more in the taking
      of clinical decisions. This would help the introduction of improvements both in
      the technical quality of treatment and in the follow-up of chronic diseases to be
      perceived as such by patients. At present, as this study suggests, they are
      causes of greater dissatisfaction.

PMID- 9557357
TI  - [Correction of social inequalities in health: reform of primary health care as a
      strategy].
AB  - OBJECTIVES: To evaluate the impact of a policy to define priorities for the
      reform of primary health care services among small areas according to health and
      social indicators. DESIGN: Qualitative study of the changes in the provision of
      primary health care services after a priority setting exercise based in social
      and a health indicators. SETTING: The city of Barcelona (Catalonia, Spain).
      PARTICIPANTS: The 66 basic health areas in which the city is divided for health
      care planning. INTERVENTION: Areas are ranked according to their health and
      social indicators, giving greater priority to those areas with unfavorable
      indicators for the development of the reform of primary health care services and
      a associated allocation of resources. RESULTS: Although at first new investments
      were determined by preexisting processes based in opportunity criteria, clear
      changes are observed. Three years after, there are improvements in the provision
      for services in all priority areas, or they are in the midst of change.
      CONCLUSIONS: In a context of tightening resources and of resistance to change, it
      is possible to introduce objective criteria to set priorities to improve primary
      health care services selectively in areas with most unfavorable indicators. This
      process has the capacity to overrun obstacles and resistances.

PMID- 9557358
TI  - [Health related life styles of the young].

PMID- 9557359
TI  - [Urinary tract infections in primary care].

PMID- 9557360
TI  - [Study of tuberculosis in Bages county between 1991 and 1995: incidence and
      monitoring].

PMID- 9557361
TI  - [Urinary tract infections in pregnant women in a rural environment].

PMID- 9557362
TI  - [Who are the authors who publish in primary care journals and where do they
      work].

PMID- 9557363
TI  - [A reasoned approach to the pharmacologic treatment of Alzheimer's disease].

PMID- 9557364
TI  - Arthritis and hepatitis.
AB  - Arthritis has a fascinating relationship with hepatitis of diverse origins.
      Either condition can predominate and the correct diagnosis may be elusive,
      especially in the early stages. Humoral autoimmune mechanisms appear to serve as
      a bridge connecting the two target organs, whether the syndromes are caused by
      viral infections or unspecified etiologies. Maintaining a keen awareness of and
      being able to recognize the clinical arthritis-hepatitis syndromes are critical,
      enabling the physician to establish accurate diagnoses, to prescribe the correct
      therapies, and to predict outcomes.

PMID- 9557365
TI  - Nonmedicinal therapies for osteoarthritis.
AB  - Given the modest efficacy of medicinal therapy for OA, nonpharmacologic therapy
      is popular. Convincing evidence exists to support the efficacy of exercise and
      muscle strengthening for patients with knee OA. Weight loss is likely to be
      effective, as are some types of biomechanical alterations, possibly including
      elastic knee supports and the use of canes and crutches. The clinical management
      of patients with OA should sample broadly from these treatments, especially
      because they may offer other health benefits as well (i.e., aerobic exercise and
      weight loss). The optimal use of these modalities requires a team approach to
      patient care, in which the physician works closely with a physical therapist and
      nutritionist. This integrated approach may lead to decreases in pain and
      disability for the patient with OA.

PMID- 9557366
TI  - [Heart-lung interaction: the "spatial" competition].

PMID- 9557367
TI  - [The echocardiographic assessment of mitral stenosis].

PMID- 9557368
TI  - Current coronary interventional practice.

PMID- 9557369
TI  - [Ventricular systolic function. The intramyocardial mechanics and the indices of
      systolic ejection: the different physiological and clinical significance].

PMID- 9557370
TI  - [Tumor necrosis factor and heart failure].

PMID- 9557371
TI  - Non-surgical myocardial ablation: for hypertrophic obstructive cardiomyopathy.

PMID- 9557372
TI  - [Collateral circulation and the coronary reserve].
AB  - The mechanisms regulating coronary collateral circulation are largely unknown
      owing to both the complex and variable nature of clinical models and the
      difficulty to obtain quantitative and differentiated flow measurements within the
      various coronary tree portions. With the aim of assessing collateral flow
      reserve, we studied 19 patients with effort angina, without myocardial infarction
      and with isolated occlusion of either the left anterior descending coronary
      artery (n = 14) or the circumflex coronary artery (n = 5). Flow values were
      measured basally, during atrial pacing induced tachycardia and following ev
      dipyridamole infusion (0.56 mg/kg of body weight in 4 min), by means of positron
      emission tomography and nitrogen-13 ammonia as flow tracer, within both regions
      depending on collateral circulation and the remote ones. Results have been
      compared with those obtained in 13 normal subjects. Basal flow values in regions
      depending on collateral circulation and in the remote regions (0.61 +/- 0.11 vs
      0.63 +/- 0.17 ml/min/g) were found to be similar, but lower than in normal
      subjects (1.00 +/- 0.20 ml/min/g, p < 0.01). During atrial pacing, flow increased
      to 0.83 +/- 0.25 and to 1.11 +/- 0.39 ml/min/g, in the regions depending on
      collateral circulation and in the remote regions, respectively (p < 0.05 as
      compared to baseline); again, values were lower than in normal subjects (1.86 +/-
      0.61 ml/min/g, p < 0.01). Dipyridamole infusion further increased flow in the
      remote regions (1.36 +/- 0.57 ml/min/g, p < 0.01 as compared to atrial pacing)
      but it did not in the regions depending on collateral circulation (0.94 +/- 0.37
      ml/min/g, NS as compared to atrial pacing); both values were lower than in normal
      subjects (3.46 +/- 0.78 ml/min/g, p < 0.01). Flow reserve in the regions
      depending on collateral circulation was found to have a direct linear correlation
      with the one in the remote regions (r = 0.83; p < 0.01). In conclusion, in spite
      of basal hypoperfusion, collateral circulation maintains a flow reserve which,
      even if reduced, is able to cope with moderate increments in oxygen consumption.
      An analogous flow reduction can be observed in the remote regions, suggesting
      that the entire coronary tree is involved, beyond the obstructive lesions of the
      main arterial branches.

PMID- 9557373
TI  - [The influence of left systolic ventricular function on right ventricular
      function after an acute myocardial infarct].
AB  - The aim of this study was to assess the interaction between left ventricular and
      right ventricular systolic function after acute myocardial infarction (AMI). The
      study population comprises 27 normal subjects and 71 patients assessed at
      predischarge (12 +/- 7 days) after AMI and divided into two subgroups, 24 with
      inferior AMI and 47 with non inferior AMI. The three groups were comparable for
      sex, age, heart rate and blood pressure. Right ventricular function was evaluated
      by two-dimensional assessment of tricuspid annular plane systolic excursion
      (TAPSE) and by Doppler analysis of right ventricular outflow tract. Left
      ventricular systolic function was evaluated by two-dimensional determination of
      ejection fraction and wall motion score index, and by Doppler analysis of left
      ventricular outflow tract. The overall AMI population showed reduced TAPSE,
      velocity-time integral (both p < 0.05) and peak velocity (p < 0.005) of right
      ventricular outflow tract, prolongation of Q-S2 interval and increase of pre
      ejection period/acceleration time ratio (both p < 0.05) in comparison with
      normals. These alterations were accompanied by a decrease of left ventricular
      ejection fraction and increase of wall motion score index. (p < 0.0001) The
      changes of right ventricular indexes were confirmed in patients with inferior AMI
      who had also lower left ventricular ejection fraction (46 +/- 9%). Functional
      parameters of the right ventricle were not significantly modified in patients
      with non inferior AMI who had greater left ventricular ejection fraction (53 +/-
      8.6%). In the overall AMI population, and in particular in inferior AMI, we found
      univariate relations between time-velocity integrals of left ventricular and
      right ventricular outflow tract and between left ventricular ejection fraction
      and TAPSE. Only in inferior AMI creatinkinase peak was related to time-velocity
      integral of right ventricular outflow tract (r = -0.59, p < 0.01). In conclusion,
      the magnitude of right ventricular systolic impairment developing after left
      ventricular AMI depends on the degree of left ventricular dysfunction, likewise
      by changes of hemodynamic load imposed to the right ventricle. AMI location and,
      only in inferior AMI, infarct extension participate in determining this
      dysfunction.

PMID- 9557374
TI  - [A failed improvement in pulmonary function and exercise capacity with carvedilol
      in congestive heart failure despite an excellent effect on left ventricular
      function].
AB  - This study was aimed at investigating in chronic heart failure (CHF) the effects
      that beta-blockade with carvedilol may have on lung function, and their
      relationship with left ventricular (LV) performance and peak exercise oxygen
      uptake (VO2p). CHF causes disturbances in ventilation and pulmonary gas transfer
      (stress failure of alveolar-capillary membrane) that participate in limiting
      VO2p. Carvedilol improves LV function and not VO2p. Twenty-one NYHA functional
      class II-III patients were randomized (2 to 1) to carvedilol (25 mg bid., 14
      patients) or placebo (7 patients) for 6 months. Rest forced expiratory volume
      (FEV1), vital capacity (VC), total lung capacity (TLC), carbon monoxide diffusing
      capacity (DLCO), its alveolar-capillary membrane component (DM), pulmonary venous
      and transmitral flows (for monitoring changes in LV end-diastolic pressure, EDP),
      LV diastolic (EDD) and systolic (ESD) dimensions, stroke volume (SV), ejection
      fraction (EF), fiber shortening velocity (VCF) were measured at baseline and at 3
      and 6 months. VO2p, peak ratio of dead space to tidal volume (VD/VTp),
      ventilatory equivalent for CO2 production (VE/VCO2), VO2 at anaerobic threshold
      (VO2at) were also determined. FEV1, VC, TLC, DLCO, DM were impaired in CHF
      compared to 14 volunteers, and did not vary with treatment. Carvedilol reduced
      EDP, EDD, ESD, and increased EF, SV, VCF, without affecting VO2p, VO2at, VD/VTp,
      VE/VCO2, at 3 and 6 months. Placebo was ineffective. In CHF, carvedilol exerts
      neutral effects on ventilation and pulmonary gas transfer and ameliorates LV
      function at rest. This proves that antifailure treatment may not be similarly
      effective on cardiac and pulmonary function; and does not contradict the
      possibility that persistence of lung impairment may contribute to lack of
      improvement in exercise performance with carvedilol.

PMID- 9557375
TI  - [Tryptase levels are elevated during spontaneous ischemic episodes in unstable
      angina but not after the ergonovine test in variant angina].
AB  - Activated mast cells are present in human coronary atheromas, as well as in the
      adventitia of patients with variant angina, and may play an important role in
      plaque rupture and coronary vasomotion. To assess whether or not activation of
      mast cells is a primary event, we measured serum levels of tryptase, a specific
      marker of mast cell activation, in 8 patients with unstable angina during a
      spontaneous ischemic episode (Group 1) and in 5 patients with variant angina
      (Group 2) during ergonovine-induced coronary spasm. Blood samples were collected
      as soon as possible after the onset of pain and ECG changes (0 min), and after 5,
      15 and 60 min. Tryptase levels in Group 1 were 0.13 U/l (range 0.017-0.44) at the
      onset of pain and significantly raised to 0.75 U/l (range 0.05-2.49) at 5 min,
      decreasing to 0.076 U/l (range 0.018-0.16) at 15 min and to 0.085 U/l (range 0.01
      0.25) at 60 min (p = 0.035). Conversely, tryptase levels in Group 2 were 0.09 U/l
      (range 0.07-0.13) at 0 min, 0.11 U/l (range 0.07-0.22) at 5 min, 0.10 U/l (range
      0.07-0.18) at 15 min, 0.11 U/l (range 0.07-0.17) at 60 min (NS). In conclusion,
      tryptase levels raise during spontaneous ischemic episodes in unstable angina,
      but not after ergonovine-provoked ischemia in variant angina, suggesting that a
      primary, yet unknown stimulus, may activate mast cells during some ischemic
      episodes in unstable angina.

PMID- 9557376
TI  - [A multimedia echocardiographic archive].
AB  - The widespread diffusion of echocardiography requires to rationalize clinical
      examination archives; the recent improvement in computer processing speed and the
      addition of image processing capabilities on standard personal computer by using
      multimedia technology provide a low-cost solution to improve video digital
      acquisition and base management. Furthermore, the diffusion of computer networks
      supports the possibility of sending images in digital format from a work station
      to another. In this study we describe the setting-up of a system for
      echocardiographic image acquisition, storage, base management and analysis based
      on a standard multimedia Macintosh personal computer using readily available not
      dedicated software. We tested the overall efficiency of this system in terms of
      time required to perform hardware and software procedures, storage capacity of
      the archive and possibility to exchange information with other wire-linked
      computer work-stations or via modem. This system has proven to require an
      acceptable time to perform all the procedures showing a high level of
      connectivity with other standard personal computer work-stations; however, some
      limitations with regard to time required in sending via modem long movie files
      need to be pointed out. In conclusion, in our experience new multimedia personal
      computer could offer to every physician with a minimum informatic knowledge the
      well known advantages of digital-video, at a reasonable cost.

PMID- 9557377
TI  - [The superior vena cava obstruction syndrome after the implantation of a
      permanent pacemaker: a clinical case report].
AB  - Occlusion of the superior vena cava is a rare but serious complication of
      transvenous endocardial pacing. We describe 1 case of superior vena cava
      obstruction associated with permanent transvenous DDD pacemaker, following local
      infection. Thrombolytic therapy was initially effective, resulting in relief of
      signs of obstruction. However systemic infection occurred 3 months later. The
      patient was subsequently submitted to surgical removal of the infected pacemaker
      apparatus. Several therapeutical options described in previous papers are
      reviewed: anticoagulants, thrombolytics, percutaneous dilatation, surgical
      removal of the catheter. In conclusion, when a chronic process induced by local
      infection is present, surgical treatment is the best therapeutical approach.

PMID- 9557378
TI  - [The hypertension specialist].

PMID- 9557379
TI  - Similarity as an explanatory construct.
AB  - Theories can be found throughout cognitive science that give an explanatory role
      to similarity. Such theories can be contrasted with those that model thought
      using abstract rules. We lay out four possible explanatory roles for similarity.
      We then review the computational pros and cons of similarity- and rule-based
      models and outline the empirical work that speaks to the psychological
      plausibility of the two frameworks. We conclude that an adequate model of human
      thought must take advantage of both the flexibility of similarity-based inference
      and the compositionality and certainty associated with rule-based inference.

PMID- 9557380
TI  - Two dogmas of conceptual empiricism: implications for hybrid models of the
      structure of knowledge.
AB  - Concepts seem to consist of both an associative component based on tabulations of
      feature typicality and similarity judgments and an explanatory component based on
      rules and causal principles. However, there is much controversy about how each
      component functions in concept acquisition and use. Here we consider two
      assumptions, or dogmas, that embody this controversy and underlie much of the
      current cognitive science research on concepts. Dogma 1: Novel information is
      first processed via similarity judgments and only later is influenced by
      explanatory components. Dogma 2: Children initially have only a similarity-based
      component for learning concepts; the explanatory component develops on the
      foundation of this earlier component. We present both empirical and theoretical
      arguments that these dogmas are unfounded, particularly with respect to real
      world concepts; we contend that the dogmas arise from a particular species of
      empiricism that inhibits progress in the study of conceptual structure; and
      finally, we advocate the retention of a hybrid model of the structure of
      knowledge despite our rejection of these dogmas.

PMID- 9557381
TI  - Similarity-based categorization and fuzziness of natural categories.
AB  - The adequacy of similarity to prototype as an account of categorization in
      natural concepts was assessed by analyzing the monotonicity of the relation
      between typicality of an item in a category and the probability of a positive
      categorization response using data from McCloskey and Glucksberg (1978). The
      analysis revealed a strong underlying similarity-based threshold curve, with
      systematic deviations. Further data collection showed that deviations from the
      curve could be attributed to the effects of unfamiliarity and non-categorical
      associations on typicality judgments, as well as differences between the
      perceptual appearance of an item (which tended to boost typicality) and its
      underlying nature (which tended to boost categorization). The results are
      discussed in terms of the different presuppositions and task constraints involved
      in rating typicality as opposed to performing a categorization.

PMID- 9557382
TI  - Alternative strategies of categorization.
AB  - Psychological studies of categorization often assume that all concepts are of the
      same general kind, and are operated on by the same kind of categorization
      process. In this paper, we argue against this unitary view, and for the existence
      of qualitatively different categorization processes. In particular, we focus on
      the distinction between categorizing an item by: (a) applying a category-defining
      rule to the item vs. (b) determining the similarity of that item to remembered
      exemplars of a category. We begin by characterizing rule application and
      similarity computations as strategies of categorization. Next, we review
      experimental studies that have used artificial categories and shown that
      differences in instructions or time pressure can lead to either rule-based
      categorization or similarity-based categorization. Then we consider studies that
      have used natural concepts and again demonstrated that categorization can be done
      by either rule application or similarity calculations. Lastly, we take up
      evidence from cognitive neuroscience relevant to the rule vs. similarity issue.
      There is some indirect evidence from brain-damaged patients for neurological
      differences between categorization based on rules vs. that based on similarity
      (with the former involving frontal regions, and the latter relying more on
      posterior areas). For more direct evidence, we present the results of a recent
      neuroimaging experiment, which indicates that different neural circuits are
      involved when people categorize items on the basis of a rule as compared with
      when they categorize the same items on the basis of similarity.

PMID- 9557383
TI  - Similarity and rules: distinct? Exhaustive? Empirically distinguishable?
AB  - The distinction between rule-based and similarity-based processes in cognition is
      of fundamental importance for cognitive science, and has been the focus of a
      large body of empirical research. However, intuitive uses of the distinction are
      subject to theoretical difficulties and their relation to empirical evidence is
      not clear. We propose a 'core' distinction between rule- and similarity-based
      processes, in terms of the way representations of stored information are
      'matched' with the representation of a novel item. This explication captures the
      intuitively clear-cut cases of processes of each type, and resolves apparent
      problems with the rule/similarity distinction. Moreover, it provides a clear
      target for assessing the psychological and AI literatures. We show that many
      lines of psychological evidence are less conclusive than sometimes assumed, but
      suggest that converging lines of evidence may be persuasive. We then argue that
      the AI literature suggests that approaches which combine rules and similarity are
      an important new focus for empirical work.

PMID- 9557384
TI  - Reuniting perception and conception.
AB  - Work in philosophy and psychology has argued for a dissociation between
      perceptually-based similarity and higher-level rules in conceptual thought.
      Although such a dissociation may be justified at times, our goal is to illustrate
      ways in which conceptual processing is grounded in perception, both for
      perceptual similarity and abstract rules. We discuss the advantages, power and
      influences of perceptually-based representations. First, many of the properties
      associated with amodal symbol systems can be achieved with perceptually-based
      systems as well (e.g. productivity). Second, relatively raw perceptual
      representations are powerful because they can implicitly represent properties in
      an analog fashion. Third, perception naturally provides impressions of overall
      similarity, exactly the type of similarity useful for establishing many common
      categories. Fourth, perceptual similarity is not static but becomes tuned over
      time to conceptual demands. Fifth, the original motivation or basis for
      sophisticated cognition is often less sophisticated perceptual similarity. Sixth,
      perceptual simulation occurs even in conceptual tasks that have no explicit
      perceptual demands. Parallels between perceptual and conceptual processes suggest
      that many mechanisms typically associated with abstract thought are also present
      in perception, and that perceptual processes provide useful mechanisms that may
      be co-opted by abstract thought.

PMID- 9557385
TI  - Similarity and the development of rules.
AB  - Similarity-based and rule-based accounts of cognition are often portrayed as
      opposing accounts. In this paper we suggest that in learning and development, the
      process of comparison can act as a bridge between similarity-based and rule-based
      processing. We suggest that comparison involves a process of structural alignment
      and mapping between two representations. This kind of structure-sensitive
      comparison process--which may be triggered either by experiential or symbolic
      juxtapositions--has a twofold significance for cognitive development. First, as a
      learning mechanism, comparison facilitates the grasp of structural commonalities
      and the abstraction of rules; and, second, as a mechanism for the application and
      extension of previously acquired knowledge, comparison processes facilitate the
      application of abstract knowledge to new instances.

PMID- 9557386
TI  - Measles control in Australia. Report of the Measles Control in Australia
      Workshop, 5 November 1997.
AB  - The proceedings of the Measles Control in Australia Workshop held on 5 November
      1998 are presented in this report. Prompted by the possibility of a global
      elimination campaign in the near future the Workshop considered the factors
      involved in elimination of measles from Australia. Epidemiology, surveillance,
      laboratory diagnosis methods, mathematical modelling, and the cost and logistics
      were all addressed. Mass vaccination for all 2-18 year olds, and a routine 2-dose
      regimen with scheduled doses at 12 months and school entry were recommended.
      Intensified surveillance, based on a sensitive case definition and laboratory
      confirmation (measles specific IgM) of suspected cases was identified as a
      crucial component of the campaign. The continuation of high vaccination coverage
      for each of the two doses would be essential to maintain elimination once
      established.

PMID- 9557387
TI  - Methodology for measuring Australia's childhood immunisation coverage.

PMID- 9557389
TI  - Gonococcal conjunctivitis outbreak.

PMID- 9557390
TI  - Communicable Diseases Surveillance.

PMID- 9557388
TI  - Immunisation and asthma.

PMID- 9557391
TI  - An overview of antigen presentation and its central role in the immune response.

PMID- 9557393
TI  - Molecular requirements for assembly and intracellular transport of class I major
      histocompatibility complex molecules.

PMID- 9557392
TI  - How do endogenous proteins become peptides and reach the endoplasmic reticulum.

PMID- 9557394
TI  - Peptide-major histocompatibility complex class I complex: from the structural and
      molecular basis to pharmacological principles and therapeutic applications.

PMID- 9557395
TI  - Immune response of beta 2-microglobulin-deficient mice to pathogens.

PMID- 9557396
TI  - CNS neurons: the basis and benefits of low class I major histocompatibility
      complex expression.

PMID- 9557397
TI  - Suppression of MHC class I antigen presentation by human adenoviruses.

PMID- 9557398
TI  - Herpesvirus evasion of the immune system.

PMID- 9557399
TI  - Intracellular transport of molecules engaged in the presentation of exogenous
      antigens.

PMID- 9557400
TI  - Biologic consequences of defective major histocompatibility complex class II
      presentation.

PMID- 9557401
TI  - Managed cost.

PMID- 9557402
TI  - Attic cholesteatoma in the anterior epitympanum.

PMID- 9557403
TI  - Varicosities and vascular masses.

PMID- 9557404
TI  - Unilateral antrochoanal polyp with bilateral nasal obstruction.

PMID- 9557405
TI  - Branchio-oto-renal syndrome (BOR syndrome, Melnick-Fraser syndrome).

PMID- 9557406
TI  - Internal auditory canal.

PMID- 9557407
TI  - Local recurrence of carcinoma of the tongue after glossectomy: patient prognosis.
AB  - We conducted a retrospective review of the prognosis for patients with local
      recurrence after surgical treatment of carcinoma of the tongue. Glossectomy for
      squamous cell carcinoma of the tongue was performed in 167 patients. Local
      recurrence developed in 32 patients including 21 with local recurrence alone, 10
      with locoregional recurrence and one with locodistant recurrence. The incidence
      of local recurrence increased with tumor stage (from 16% of T1 tumors to 46% of
      T4 carcinomas). Eleven (34%) patients underwent surgical salvage for local
      recurrence, with only one (9%) patient surviving free of carcinoma at 43 months
      post-surgical salvage. All of the remaining 21 patients with local recurrence
      were treated palliatively and all died within one year. Patients who underwent
      surgical salvage had significantly higher survival rates compared to those
      treated palliatively. Close follow-up after glossectomy is important for early
      detection of local recurrence amenable to surgical salvage. However, the overall
      prognosis for patients with local recurrence was poor, with a three-year
      actuarial survival rate of only 3%. Therefore, prevention of local recurrence
      with adequate initial surgical treatment is essential.

PMID- 9557408
TI  - Conservative management of traumatic pseudodiverticulum in the neonate.
AB  - Traumatic pseudodiverticulum of the pharynx is an uncommon entity which generally
      occurs in infants after traumatic intubation or suctioning. A case of an infant
      presenting with stridor, drooling and cervical crepitus is presented.

PMID- 9557409
TI  - Revision endoscopic sinus surgery: the Thomas Jefferson University experience.
AB  - Since its introduction, functional endoscopic sinus surgery (FESS) has
      demonstrated success rates of 76% to 98%. A small group of the patients in whom
      initial FESS and optimal medical therapy fail require revision endoscopic sinus
      surgery (RESS). This group has recently been studied by several authors, and we
      have evaluated a group of 90 RESS patients selected from 753 consecutive primary
      FESS patients. Patients were followed for a mean of 22.8 months. Extent of
      disease, history of polyps, allergy, previous traditional endonasal sinus
      surgery, male gender, chronic steroid use, and the presence of a deviated septum
      all appeared to adversely affect RESS outcome. The surgeon's knowledge of the
      sinus anatomy is critical, especially in revision sinus cases in which landmarks
      are distorted or absent. In our review, RESS was associated with a 1% major
      complication rate and was successful in 67% of patients. Computer-assisted
      endoscopic sinus surgery integrates preoperative imaging with realtime endoscopic
      visualization, augments the surgeon's knowledge of anatomy, and helps to minimize
      patient risk.

PMID- 9557410
TI  - Internal jugular vein thrombophlebitis.

PMID- 9557411
TI  - Fungal sinusitis: progression of disease in immunosuppression--a case report.
AB  - Fungal sinusitis is a disease which can be grouped into invasive and noninvasive
      forms. The invasive entities include the acute/fulminant and chronic/indolent
      forms. The noninvasive entities include the fungus ball and allergic forms. The
      noninvasive forms, however, can develop into invasive disease under certain
      immunosuppressive states. The patient in this case report had the fungus ball
      form of fungal sinusitis which evolved into chronic, and then the acute/fulminant
      form approximately two weeks after undergoing cadaver-donor kidney
      transplantation. Due to the patient's immunosuppressed state, the fungus spread
      beyond the sinus region and eventually lead to fulminant disseminated disease.
      The severity of the fungal disease corresponded directly to the severity of the
      patient's immunosuppression.

PMID- 9557412
TI  - Animal bites to the head and neck.
AB  - There is controversy regarding the timing of repair and the use of prophylactic
      antibiotics in patients with animal bites to the head and neck. In this paper we
      review our experience with such wounds, and address surgical management and the
      use of prophylactic antibiotic therapy. A retrospective review of the medical
      records of 29 patients with animal bites to the head and neck was conducted. All
      patients were seen and treated at a large teaching hospital in Houston, Texas
      over an 18-month period. Seventy-six percent of our patients were 12 years old or
      younger. Most came to the emergency room soon after sustaining their injuries,
      and their wounds were repaired primarily with favorable results. There were no
      cases of wound infection. Ninety percent were treated with prophylactic
      antibiotics. The wounds of the 10% of patients who did receive antibiotics were
      similar to those of the other patients and healed well without infection. Wounds
      resulting from animal bites to the head and neck can be repaired primarily when
      treated shortly after injury. Further prospective, randomized studies are
      recommended to evaluate the effectiveness and necessity of prophylactic
      antibiotic therapy in this patient population.

PMID- 9557413
TI  - Oat cell carcinoma of the tongue from an unknown primary.
AB  - Oat cell carcinoma is rarely diagnosed in the head and neck and can be primary or
      secondary. Primary tumors arise from amine precursor uptake and decarboxylation
      cells which are found throughout the head and neck. Secondary deposits
      metastasize most commonly from the lungs. We report a 64-year-old woman with a
      known pancreatic oat cell carcinoma who came to the ENT Department with
      dysphagia. On examination, a lesion was seen at the base of the tongue and was
      histologically an oat cell carcinoma. No treatment was administered and the
      patient died one month after discharge. This report highlights the difficulty in
      determining the primary site when a rare tumor metastasizes to the head and neck
      and no autopsy findings are obtained. To our knowledge, oat cell carcinoma of the
      tongue has not been previously reported.

PMID- 9557414
TI  - Blood lipids.

PMID- 9557415
TI  - Impact of user fees in health.

PMID- 9557416
TI  - Impact of user charges on government health facilities in Tanzania.
AB  - Utilisation of outpatient services in government owned district hospitals in Dar
      es Salaam, declined by more than 50% following the introduction of user charges
      in these health facilities in mid July 1993. Outpatient attendances in the
      private health facilities studied remained constant throughout the year although
      these charged higher fees. Education and employment status were found to be major
      factors influencing utilisation of public versus private health facilities.
      Public facility users (62.8%) had five to eight years of formal education.
      Private facility users with five to eight years of education were 45.5% and those
      with more than years of education were 47.1%. While 68.6% of public facility
      users paid for their own healthcare, more than a quarter (27.3%) had their costs
      met by relatives or friends. The employer paid for 72% of private facility users,
      49.2% of whom stated that this was the reason why they used private facilities.
      Despite introduction of charges in public hospitals, availability of prescribed
      medication was poor. Drugs were reported to be always available by only 27.3% of
      public health facility users compared to 80% of private health facility users.

PMID- 9557417
TI  - Re: Malaria treatment in peri-urban area of Kisumu town.

PMID- 9557418
TI  - Assessment of rational drug use and prescribing in primary health care facilities
      in north west Ethiopia.
AB  - A study on rational drug use was undertaken in nine health centres (HCs) and nine
      health stations (HSs) in Ethiopia. Prescribing, patient care and facility
      specific factors were measured using drug use indicators. Prescribing patterns of
      drugs were also assessed. With only few exceptions, the drug use indicators in
      HCs and HSs and between retrospective and prospective studies were similar
      despite differences in manpower and facilities. The average consultation time (in
      minutes) in HSs and HCs was 5.1 +/- 0.8 and 5.8 +/- 1.06, respectively. The
      dispensing time (in minutes) was 1.5 +/- 0.7 in HSs and 1.9 +/- 0.6 in HCs. Both
      patient care indicators seem to be adequate to influence patient satisfaction to
      the overall health service and patient knowledge of important dosage
      instructions. Most drugs (more than 89% in HCs and 71% in HSs) were actually
      dispensed from the health facilities and labelling was satisfactory. Prescribing
      by generic names (average: 75% in HCs and 83% in HSs) was encouraging. While the
      availability of key drugs was ensured, essential documents were missing in most
      facilities or they were unpopular for use, and those available required revision
      and updating. Polypharmacy in which the number of drugs/encounter was < 2.5 was
      minimal, but that a large proportion of the prescriptions contained two or more
      drugs could result in adverse drug-drug interactions. The most frequently
      prescribed drugs were anti-infectives and analgesics accounting for over 76% in
      HCs and 82% in HSs and in most cases they are probably prescribed with little
      justification. The exposure of patients to antibiotics (average: 60% in HCs and
      65% in HSs) was unacceptably high to justify epidemiological trends. The high
      exposure of patients to injections, especially in the HSs (over 37%), should be
      seen from the health and economic points of view. The results revealed priority
      areas for intervention. They also provide standard references to compare drug use
      situations and their change over time in different settings, area and time in
      Ethiopia.

PMID- 9557419
TI  - Sexually transmitted disease risk assessment used among low-risk populations in
      east central Africa: a review.
AB  - In sub-Saharan Africa where sexually transmitted diseases (STDs) are prevalent
      but health resources are scarce, algorithms that act as STD/HIV risk assessment
      (RA) tools for family planning (FP) and maternal/child health (MCH) clinic
      attenders may be useful. These RA algorithms generally comprise questions about a
      person's social, economic, demographic, behavioural and clinical background. The
      answers can be scored or scaled to indicate a higher probability of current
      STD/HIV infection and thus the need for testing or treatment. RA can be done
      alone, or can be combined with clinical examination where laboratory diagnosis is
      not feasible. But how accurate are RA tools? We reviewed six studies at African
      sites that examined the use of RA combined with a clinical algorithm for STD
      screening of clinic attendees. Researchers reported the standard measures of test
      accuracy: sensitivity (per cent of infected women found positive by the tool);
      specificity (per cent of uninfected women found negative by the tool), and
      positive predictive value (per cent of women found positive by the tool who are
      truly infected). Most algorithms had low sensitivity (< 50%) and low positive
      predictive value (< 20%). The addition of clinical examination, and of leucocyte
      esterase (LE) testing, improved accuracy. But algorithms that performed well in
      one site were less accurate at other sites. For illustrative purposes, we
      considered a hypothetical population of 1,000 women attending a FP clinic. With a
      prevalence of cervical gonorrhoea of five per cent, algorithm sensitivity of 40%,
      and algorithm specificity of 75%, the positive predictive value of the RA tool
      would be 7.7%. In other words, 20 (7.7%) women diagnosed as infected would
      actually have gonorrhoea, and 237 false positive women would be treated
      needlessly, with the attendant costs and risks. However, with a disease
      prevalence above 50%, as might prevail for vaginal infections, and the same
      sensitivity and specificity figures, the positive predictive value may reach 70
      80%. Risk assessment appears to be a relatively easy way to integrate STD
      management into family planning and MCH practice. However, there is no evidence
      to show its effectiveness for screening low-risk populations. We urge improvement
      of these tools, including information on the behaviour of male partners, and
      addition of simple screening tests such as leucocyte esterase dipsticks.

PMID- 9557420
TI  - Socio-cultural and economic aspects of AIDS in Uganda: a review.
AB  - AIDS is long-established in Uganda; prevalence rates are high. Most transmission
      is by heterosexual intercourse, and has been associated with population
      movements, especially of traders. Treatment resources are very limited and
      expensive. Some sexual practices inhibit contraceptive use. Attitudes towards
      AIDS and its testing reveal contradictions, although contraceptive knowledge is
      widespread. Folk beliefs have not been studied. Government guidelines have been
      produced, although these do not inform clinical attitudes. Indications suggest
      that prevalence in the long-term may be decreasing.

PMID- 9557421
TI  - Comparison of protection afforded by single measles vaccination and late
      revaccination schedules.
AB  - An intervention study compared the protection afforded vaccinees by single
      measles vaccination and late revaccination schedules in 1990-94. During the
      intervention a single revaccination (after initial vaccination at nine months of
      age) was applied to children at any point in time between 12 and 23 months of
      age. Cases of measles aged 10-23 months were identified through an active
      surveillance system and in this period 5, 11 and 11 cases of revaccinated, single
      vaccination and unvaccinated children were identified. Measles incidence rates
      were 392.2-415.6 (mean = 405.6, SD = 6.7), 75.4-112.1 (median = 91.7, SD = 13.3)
      and 12.8-15.2 (mean = 13.9, DS = 0.99) per 100,000 population in children who
      were unvaccinated, with single vaccination and revaccinated respectively.
      Relative risk of contracting measles in children who were unvaccinated or with
      single vaccination was 26.5-32.5 (mean = 29.4, SD = 2.3) and 5.8-8.8 (mean = 6.8,
      SD = 1.2) respectively compared with revaccinated children. Vaccine efficacies
      that were determined were 73-81% (mean = 77.2, SD = 2.9) and 96.2-96.9% (mean =
      96.6, SD = 0.27) for single vaccination and late revaccination schedules
      respectively. It was concluded that late revaccination affords vaccinees better
      protection than single vaccination through improvement in vaccine.

PMID- 9557422
TI  - Epidemiological features of severe paediatric malaria in north western Ethiopia.
AB  - Malaria remains a major public health challenge in sub-Saharan Africa, yet our
      knowledge of the epidemiology of malaria in terms of patterns of mortality and
      morbidity is limited. To examine the clinical and epidemiological presentation of
      severe life-threatening malaria in Humera, north western Ethiopia studies were
      conducted among the childhood population in the community, those presenting to
      out-patient facilities and those admitted to the district hospital. The overall
      P. falciparum parasite rate among children aged 0-9 years resident within the
      area was only 12% confirming the low level of endemicity in this area. P. vivax
      infections were present in 5% of children. Between July 1993 and June 1994 peak
      out-patient presentation with Plasmodium falciparum coincided with the rains with
      over 50% of cases occurring between August and October whilst P. vivax infections
      were predominant during the hot, dry months. Malaria was an important cause of
      paediatric admission to the local district hospital with an estimated 4.7% of the
      at-risk childhood community warranting intensive clinical management each year.
      Case fatality rates were high and the clinical spectrum of severe disease
      indicated a preponderance of cerebral malaria cases. In addition, respiratory
      distress was a feature in 12% of the malaria admissions. The suggestion that the
      coexistence of Plasmodium falciparum and Plasmodium vivax may serve to reduce the
      severe clinical consequences of P. falciparum malaria is not supported by these
      observations.

PMID- 9557423
TI  - T-lymphocytopaenia, opportunistic infections and pathological findings in
      Ghanaian AIDS patients and their sexual partners.
AB  - Ninety-nine patients at Center for Disease Control (CDC) clinical stage IV were
      studied. Twelve (12.12%) of these patients turned out to be HIV seronegative. Ten
      out of the 12 HIV negative patients were immunocompetent whereas the other two
      had proportional decreases in both CD4+ and CD8+ T-lymphocytes. HIV-1, HIV-2, and
      dual infection, were detected in 51.5%, 2%, and 22.2% respectively of clinical
      AIDS patients. The other 12.12% of clinical AIDS patients were indeterminate for
      HIV antibodies. All HIV positive patients with the exception of two, were
      immunocompromised with respect to CD4+ and CD8+ T-lymphocyte counts. Two healthy
      spouses and three children of patients who died from the disease were
      seronegative for HIV antibodies. Herpes simplex virus type 2 (HSV-2) and
      cytomegalovirus (CMV) antibody titres were higher in HIV infected than uninfected
      blood. Patients with chronic diarrhoea, lymphadenopathy, pneumonia, and
      tuberculosis, either alone or in combination of two or more of such symptoms,
      were found to be more likely to be confirmed by serology and immunology as
      definitive AIDS patients in Ghana. In postmortem studies on 20 patients,
      pneumonia due to tuberculosis constituted the major cause of death.
      Toxoplasmosis, cytomegaloviral eosophagitis and enteritis, and cryptococcosis
      were the major opportunistic infections detected. Programmed cell death
      (apoptosis) was found by the DNA gel electrophoresis method to be an unlikely
      major mechanism of accelerated culture induced death of PBMCs from CDC stage IV
      AIDS patients.

PMID- 9557424
TI  - Duration of symptoms and case fatality of sleeping sickness caused by Trypanosoma
      brucei rhodesiense in Tororo, Uganda.
AB  - Although there have been recent molecular biological studies for evidence of
      possible changes in trypanosome biochemistry, such studies are not yet
      complemented by parallel clinical studies to determine the possible implications
      to the sleeping sickness patient. The study of the duration of symptoms and the
      case fatality of T. b. rhodesiense showed that the disease progressed to the
      stage of central nervous system involvement between three weeks to two months of
      infection. Most (> 80%) deaths occurred within six months of illness. The case
      fatality rate of treated sleeping sickness patients was 6% of which the rate in
      the late-stage of sleeping sickness was more than two and a half times that in
      the early stage. The incidence of melarsoprol encephalopathy was 2.5% and case
      fatality due to this condition was 1.0% and similar to previous findings. Thus it
      appears the virulence of T. b. rhodesiense circulating in south east Uganda has
      not changed during the past decades.

PMID- 9557425
TI  - Perforation of terminal ileum and appendix in typhoid enteritis: report of two
      cases.
AB  - Two cases of simultaneous typhoid perforation of terminal ileum and appendix are
      reported from Harare Central Hospital. These findings have not been reported
      before. Perforations were associated with schistosomiasis and HIV/AIDS.
      Definitive diagnosis was made only after laparotomy, serology and histopathology.
      With early diagnosis, effective resuscitation and timely intervention, this life
      threatening condition is not necessarily fatal. Septic shock is however, an
      ominous sign of poor prognosis. In the tropics, bradycardia, leukopaenia and
      perforation in a febrile patient with right iliac fossa tenderness should arouse
      suspicion. Perforations may occur in patients with underlying diseases.

PMID- 9557426
TI  - Complications of typhoid perforation of the ileum in children after surgery.
AB  - Sixty six consecutive cases of typhoid perforation of the ileum in children
      between the ages of four and 14 years were analysed. 62.1% of the children were
      boys and 37.9% girls, a boy/girl ratio of 1.6:1.0. Postoperative complications
      included: wound infection, gaped wounds, intestinal obstruction secondary to
      adhesions, wound dehiscence and pneumonia. The most serious complication was
      enterocutaneous fistula and the most frequent was wound infection. These
      postoperative complications adversely affected the morbidity and mortality rates
      of these severely ill and debilitated patients with typhoid perforation of the
      ileum--a serious complication of enteric fever.

PMID- 9557427
TI  - Evaluation of the efficacy of thiamine and pyridoxine in the treatment of
      symptomatic diabetic peripheral neuropathy.
AB  - The clinical response to therapeutic doses of two vitamins were determined in
      diabetic patients with symptomatic peripheral neuropathy. Of 200 consecutive
      patients, 100 were randomly allocated to treatment with both thiamine (25 mg/day)
      and pyridoxine (50 mg/day) group A and the rest group B to treatment with an
      identical tablet containing 1 mg/day each of thiamine and pyridoxine. Pain,
      numbness, paraesthesia and impairment of sensation and ankle in the legs were
      graded into none, mild, moderate or severe. Blood thiamine levels were measured
      using HPLC fluorimetry. Four weeks after starting treatment the grade was less
      than on the first visit in 88.9%, 82.5% and 89.7% of those whose worst symptoms
      were pain, numbness and paraesthesia respectively for group A compared with
      11.1%, 40.5% and 39.4% respectively for group B. The severity of signs of
      peripheral neuropathy decreased in 48.9% of patients in group A compared with
      11.4% in group B. The mean (s.e.) pre-treatment whole blood thiamine levels
      decreased with increasing severity of symptoms: 64.2 (2.81), 57.7 (3.25) and 52.2
      (2.14) micrograms/l for those with mild, moderate and severe symptoms
      respectively (analysis of variance, p = 0.03). Diabetic peripheral neuropathy in
      Dar es Salaam is associated with thiamine deficiency. Dietary guidelines for
      diabetic patients should emphasize a balanced diet.

PMID- 9557428
TI  - Frequency of foetal haemoglobin and haemoglobin values in various haemoglobin
      genotypes in Calabar, Nigeria.
AB  - The frequency of foetal haemoglobin (HbF) and haemoglobin (Hb) levels were
      determined among 108 subjects with different haemoglobin genotypes in Calabar,
      between March and October, 1996. Hb-genotype was determined using the cellulose
      acetate method, while HbF and Hb were estimated using the modified Betke alkaline
      denaturation method and cyanmethaemoglobin techniques respectively. Haemoglobin
      genotype SS individuals had the highest mean HbF concentration of (3.05 +/- 1.61)
      as compared to AA and AS subjects with means of 0.195 +/- 0.25 and 1.072 +/- 0.98
      respectively. This relationship was statistically significant (P < 0.02). On the
      other hand, AA subjects had the highest mean haemoglobin concentration (12.79 +/-
      1.19) while SS subjects had the lowest (10.65 +/- 2.06). This study has indicated
      the persistence of HbF into adult life in this locality. Since HbF is associated
      with natural anti-sickling properties, its role as a monitoring factor in the
      management of sickle cell anaemia is examined in detail.

PMID- 9557429
TI  - Pattern of surgical admissions in Gondar Teaching Hospital, Ethiopia.
AB  - A retrospective study based on the principal discharge diagnosis of 4121 surgical
      in-patients, who were admitted to Gondar College of Medical Sciences Hospital
      over a three year period, is made to document the commonest surgical conditions
      prevalent in the north west region of Ethiopia. Intestinal obstruction was the
      commonest cause of surgical admission followed by head injury and soft tissue
      injury.

PMID- 9557431
TI  - Nephrotic syndrome in Nigerian children with homozygous sickle cell disease.
AB  - Two hundred and seventy two children with the nephrotic syndrome were seen and
      followed up at the Paediatric Renal Unit of the University of Nigeria Teaching
      Hospital, Enugu over 12 1/2 year period, between June 1983 and December 1995. Of
      these, there were nine (3.3%) children with homozygous sickle cell disease (SS).
      This latter group had a mean age of 9.6 +/- 3.2 years, male to female ratio of
      1:2 and serum cholesterol of 3.13 +/- 1.48 mmol/l at the time of diagnosis. The
      mortality rate was 55.6% in these sicklers, death occurring within one and a half
      to five years of diagnosis. Causes of death were attributable to sickle cell
      disease in 60%, renal diseases in 20%, and other causes in 20%. Renal biopsy in
      two of the sicklers showed membrano-proliferative glomerulonephritis (MPGN) and
      focal glomerulosclerosis (FGS) respectively. Homozygous sickle cell disease does
      seem to predispose to the development of the nephrotic syndrome and those that do
      develop nephrotic syndrome exhibit some special characteristics, when compared to
      non-sicklers with nephrotic syndrome. These include older age of onset of the
      nephrotic syndrome, reverse sex ratios, lower serum cholesterol, higher mortality
      rate and sickle cell complications rather than chronic renal failure as the major
      cause of death.

PMID- 9557430
TI  - Evaluation and planning in national tuberculosis control programmes: the
      usefulness of the standardised patient treatment card.
AB  - Through systematic evaluation of information contained in tuberculosis patients
      treatment cards, we present an example of a rapid operations evaluation method
      for identifying issues important to a national tuberculosis programme (NTP).
      Analysis of all 279 treatment cards of patients scheduled to attend one specific
      clinic day was made ((Kinondoni district in Dar es Salaam, Tanzania). Two hundred
      and twenty five patients (81%) were diagnosed as having pulmonary tuberculosis.
      Males accounted for 61% of cases. Ninety two per cent were cases without prior
      history of treatment. Of all patients, those under 15 years and those aged 25 to
      54 years were more likely to be sputum smear-negative compared with other age
      groups. A chest radiograph was obtained as recommended to support the diagnosis
      in only 61 (38%) of 160 cases diagnosed as sputum smear-negative pulmonary
      tuberculosis. Initial drug dosing based on weight (mg/kg) revealed frequent
      dosing errors of isoniazid (97%) and pyrazinamide (65%), almost exclusively
      overdosing, in sputum smear-positive patients. Systematic examination of patient
      treatment cards provided usefull information and raises issues important to NTP
      planning and operations. Weaknesses in the execution of the national programme in
      Dar es Salaam were identified: the under-utilisation of chest radiography to
      diagnose sputum smear-negative tuberculosis and overdosing of certain drugs.

PMID- 9557432
TI  - Aetiological and epidemiological aspects of acute head injury in Malawi.
AB  - One hundred and four patients (88 males and 16 females) with acute head injuries
      admitted to the Queen Elizabeth Central Hospital, Blantyre from July 1st to
      December 31st 1995 were prospectively studied using a questionnaire. Forty seven
      (45.2%) of the injuries were caused by road traffic accidents, 42(40.4%) by
      assaults, nine (8.7%) resulted from falls from heights, two (1.9%) from
      occupational injuries and the remaining four (3.8%) were of miscellaneous
      origins. RTA associated head injuries involved 17 (36.2%) pedestrians; 14 (29.8%)
      vehicular passengers, 10 (21.3%) pedal cyclists; five (10.6%) drivers and one
      motor cyclist. Malawi males aged between 20 and 29 were mostly involved. Assault
      related head injuries occurred also in young adult males commonly at the weekend
      with more than 50% occurring on Saturday and Sunday. Fifty per cent were
      sustained at home, a quarter on the streets and surprisingly few at drinking
      houses making them the safest place to be in Malawi to avoid assaults! Alcohol
      usage was not statistically significant among those assaulted; it was not
      possible to define its aetiological role among assailants. The head injuries
      associated with falls from heights (FFH) involved eight males and one female;
      five were children. Strategies for the prevention of assaults, the various types
      of road traffic accidents and falls from heights are discussed.

PMID- 9557433
TI  - Drug induced rhabdomyolysis: case report.
AB  - Rhabdomyolysis results from skeletal muscle injury leading to the release of
      intracellular contents into blood and urine. Its diverse aetiology includes
      severe exercise, muscle trauma or ischaemia, metabolic disorders, infections and
      exposure to drugs and toxins. Known risk factors include heredity disorders of
      glycogen and lipid metabolism as well as a history of substance abuse. A case of
      rhabdomyolysis associated with exposure to opiates and benzodiazepines is
      described and the pathogenesis and treatment are reviewed. The rhabdomyolysis was
      complicated by acute renal failure; the patient fully recovered. It is suggested
      that rhabdomyolysis should be borne in mind in patients presenting with altered
      mental status, or fluid and electrolyte abnormalities, in particular, if they
      also give a history of substance abuse.

PMID- 9557434
TI  - Alcohol-related road traffic accidents.

PMID- 9557435
TI  - Drinking and driving in an urban setting in Kenya.
AB  - A roadside alcohol prevalence survey of drivers randomly selected from the
      general traffic was conducted in Eldoret, Kenya. Blood alcohol concentration
      (BAC) data obtained by a breath test in 90% of the sample (n = 479) was analysed
      by demographic and travel characteristics. 19.9% had a positive breath test (BAC
      > or = 5 mg%), 8.4% had BACs greater than 50 mg%, and 4% exceeded 80 mg%. A
      greater proportion of males (20%) had been drinking compared to females (12.5%):
      all drivers with high BACs (> or = 50 mg%) were males. The likelihood of having
      consumed alcohol was greater in motorists aged 25 years and above (20.4%) than in
      younger drivers aged 16-24 years (15.4%), their mean BACs were also more elevated
      (57 mg% versus 31 mg%). In comparison to operators of public service vehicles
      (PSV), people driving personal cars were more than twice as likely to have been
      drinking: with 21.9% being BAC positive against 10.8% (OR = 2.3; 95% CI, 1.0 to
      6.3, p = 0.05). Educated individuals with skilled careers tended to indulge in
      drink-driving to a greater extent than professional drivers (operators of public
      transport, taxi and heavy goods vehicles), with BAC prevalence rates of 23.7% and
      15.5%, respectively. Other circumstances influencing the probability of drink
      driving were number of vehicle occupants, distance to destination, road location,
      time of the night and whether it was a weekend or weekday. These findings are
      discussed in relation to the potential for promotion of relevant deterrent
      measures, including the establishment of an appropriate BAC legal limit for
      drivers in Kenya.

PMID- 9557436
TI  - Nutritional status of rural children in the Lesotho Highlands.
AB  - A baseline cross-sectional study was done to evaluate the nutritional status of
      the population of the Mohale Dam catchment area before construction of the dam
      commenced. In this article we report on the anthropometric, clinical and dietary
      assessment of the children less than 15 years of age in the study population. A
      two stage stratified sampling technique was used to randomly select 29 of the 83
      villages in the study area. Children under 15 years of age from 395 households,
      representing approximately 50% of households in the selected villages, were
      included in the study. Anthropometric measurements of body height and weight in
      relation to age and sex indicated undernutrition varying, with few exceptions,
      from high to very high levels in children under 15 years. Stunting, indicating
      chronic undernutrition, was of particular concern in children, even from the
      first year of life. Very few clinical signs of nutritional deficiencies were
      found except for a goitre prevalence of 17.5% in 10 to 14 year old children. This
      was supported by the very low urinary iodine excretion (median 1.3 micrograms/dL)
      which indicated a severe iodine deficiency. Dietary evaluation showed high
      initiation rates of breastfeeding as well as a long duration of breastfeeding.
      Complementary foods were introduced at an early age, resulting in low exclusive
      breastfeeding rates. Regular meals were reported but qualitative analysis of the
      diet showed that a too small variety of foods were eaten, with an irregular
      intake of protein-rich foods and milk. Quantitative data on 3- < 5-year-old
      children showed that micro-nutrient intakes were low and that the energy intake
      of these children was inadequate. The results showed that these nutritionally
      vulnerable children should be monitored for the impact of the dam construction on
      their nutritional status.

PMID- 9557437
TI  - Factors influencing completion of treatment among tuberculosis patients in
      Mbarara District, Uganda.
AB  - An organised TB treatment programme was started in Uganda in 1989. A cohort
      analysis of treatment outcome among 1400 patients seen in Mbarara district in
      1995 showed a very low compliance rate of 56% and this study attempted to look at
      operational factors that may be associated with this low compliance rate. The
      factors that are associated with enhanced completion of treatment include; being
      smear positive: use of short course chemotherapy; previous TB treatment; if
      patient returned for repeat smear; if patient did not change unit; and if patient
      did not change district. Gender and age were not associated with compliance. On
      unconditional logistic regression, previous TB treatment and being smear positive
      were found not to be statistically significant. Change of health unit after
      intensive phase showed the highest risk, with an adjusted odds ratio of 22.31. Of
      the significant factors only use of standard chemotherapy and change of health
      unit after intensive phase can be altered to improve compliance.

PMID- 9557439
TI  - Major congenital malformations among neonatal referrals to a Nigerian university
      hospital.
AB  - Major congenital malformations are unrecognised as a major cause of neonatal
      morbidity in many African countries. We have studied the contribution of major
      congenital malformations to morbidity among neonates referred to the University
      College Hospital, Ibadan, Nigeria over a four year period (1992-1995). Major
      congenital malformations were found in 11.1% of 1276 neonatal referrals and
      ranked fourth among the most common problems in such neonates (after sepsis,
      jaundice and tetanus but ahead of prematurity and perinatal asphyxia). The
      commonest malformations seen included spina bifida (22.5%), anorectal
      malformation (13.4%), omphalocoele (9.9%) and tracheo-oesophageal fistula (8.5%).
      Neonates with major congenital malformations presented significantly earlier than
      other neonates but mortality during the first admission was similar in the two
      groups. It is concluded that major congenital malformations pose a significant
      burden of morbidity in referred neonates to the hospital. Health services
      planners should take this into account in order to allocate the necessary
      resources for the diagnosis and management of such children.

PMID- 9557438
TI  - Exercise-induced bronchospasm: a pilot survey in Nairobi school children.
AB  - Exercise-induced bronchospasm (EIB), a common feature of asthma in children, has
      been used as the outcome measure in community-based surveys of childhood asthma
      to circumvent difficulties arising from relative lack of objectivity in the use
      of questionnaires in communities with different cultural and language
      orientations. We report here the results of the first community-based study of
      childhood asthma in Kenya using EIB as the outcome measurement. The data was
      collected in a pilot study to develop methodology for a larger subsequent study.
      The survey targeted grade four children in five Nairobi City Council school each
      representing a neighbourhood social economic status (SES). Out of 597 eligible,
      408 children took part in the study (68% participation rate). EIB defined as
      decline in FEV1 of 15% or more, post-exercise was found in 10.5% (95% CI; 10.3,
      10.7) of the children studied, the highest rate reported so far in Africa. While
      boys were more likely to exhibit EIB compared to girls, the prevalence of EIB
      tended to decrease with age, especially among children residing in low SES
      neighbourhoods where the EIB prevalence rates tended to be lower compared to
      those among children from higher SES neighbourhoods. However, none of these
      differences was statistically significant. This study confirms the feasibility of
      undertaking exercise challenge tests in the African context and we recommend that
      additional studies of similar nature be carried out in other populations of
      Africa to explore the potential of using an exercise test as a marker of asthma
      in epidemiologic studies.

PMID- 9557441
TI  - HLA-antigens in black patients with hepatocellular carcinoma.
AB  - To determine whether genetically determined immune response factors could be
      involved in the pathogenesis of hepatocellular carcinoma, we performed HLA-A and
      HLA-B typing in 55 black patients with histologically-proven hepatocellular
      carcinoma, and HLA-DR and HLA-DQ typing in 47 of these patients. The HLA typing
      was also carried out in a control group of normal black patients. The HLA typing
      was done by a standard microlymphocytotoxicity method. No difference in HLA-A,
      HLA-DR and HLA-DQ frequencies between patients and controls were noted. HLA-B21
      was present in 10.9% of patients compared to 1.8% of control subjects (corrected
      p < 0.005; relative risk = 6.6) and HLA-B49 was present in 7.3% of patients
      compared with 1.1% of normal control subjects (corrected p < 0.007; relative risk
      = 7.1). These findings suggest that genetic factors may play a role in the
      pathogenesis of hepatocellular carcinoma.

PMID- 9557442
TI  - Antibiotic resistance of prevalent Salmonella and Shigella strains in northwest
      Ethiopia.
AB  - Salmonella and Shigella strains were isolated prospectively from in- and
      outpatient specimens of the Gondar College teaching hospital over a two year
      period, from June 1994 to May 1996. Of 7993 miscellaneous specimens cultured, 80
      yielded Salmonella and 147 Shigella. Serogroup B dominated among the salmonella,
      accounting for 61% of isolates, followed by S. typhi (21%). S. flexneri (58.5%)
      and S. dysenteriae (36.7%) were the most frequently isolated species among the
      Shigella. Results of sensitivity testing to five commonly used antibiotics in the
      area: ampicillin, chloramphenicol, gentamicin, tetracycline and cotrimoxazole,
      showed multiple drug resistance among the isolates of both salmonella and
      shigella. Only 4% of shigella were sensitive to all five antibiotics screened for
      in the study. Overall sensitive of shigella isolates to individual antibiotics
      was 8.8% to tetracycline, 10% to ampicillin, 28% to co-trimoxazole and 98% to
      gentamicin. No resistance was observed to nalidixic acid among 108 shigella
      strains tested for this antibiotic. The continued sensitivity of S. typhi to
      chloramphenicol, cotrimoxazole, ampicillin and the other commonly used
      antibiotics is noted. It is recommended that nalidixic acid be introduced into
      the area under strict regulation for treatment of severe cases of shigella
      dysentery, an illness which is highly endemic in the region and the cause of
      occasional epidemics with high mortality.

PMID- 9557440
TI  - Cardiac abnormalities in children with malignancies at Kenyatta National
      Hospital.
AB  - This was a cross-sectional survey in which 80 children with malignancies were
      studied at the Kenyatta National Hospital to determine cardiac status before and
      during cancer therapy. An equal number of age and sex matched subjects admitted
      to the surgical wards for minor procedures was recruited as a comparison group.
      All the subjects underwent clinical cardiac assessment. Chest radiographs,
      electrocardiograms (ECG), echocardiograms, haemograms and renal function tests
      were also performed. Overall, 13 cases (16.3%) had abnormal cardiac findings
      compared to 7 (8%) in the comparison group (p = 0.429). Sixteen, two and five
      subjects had abnormal velocity of circumferential fibre shortening, ejection
      fraction and pericardial effusion respectively. Three out of the five subjects
      with pericardial effusion were cancer patients who had not undergone treatment.
      Mitral valve prolapse with regurgitation was diagnosed in one cancer patient.
      Though not statistically significant, children with malignancies appear to have a
      higher frequency of acquired cardiac abnormalities than those without cancers.
      Since a larger proportion of the abnormalities occurred in cancer children before
      commencement of treatment, the pathology is more likely to have resulted from the
      malignancies than therapy. There was no evidence to suggest that cancer treatment
      contributed to cardiac morbidity. We recommend that all oncology patients undergo
      cardiac evaluation on admission.

PMID- 9557443
TI  - Intraleucocyte malaria pigment in asymptomatic and uncomplicated malaria.
AB  - While malaria pigment or haemozoin is known to be an end product of haemoglobin
      digestion by the malaria parasite, its clinical significance is just beginning to
      be elucidated. We have studied the distribution of intraleucocyte malaria pigment
      in 92 children, consisting of 32 children with asymptomatic malaria, 32 children
      with mild or uncomplicated malaria and 28 children with no malaria. Over 90% of
      children in each of the three groups had pigment-containing monocytes and the
      numbers of pigment-containing monocytes were not significantly different between
      the three groups. While over 90% of children in both the asymptomatic malaria and
      uncomplicated malaria groups had pigment-containing neutrophils, 71.4% of the no
      malaria group had such neutrophils. The numbers of pigment containing neutrophils
      was highest in the uncomplicated malaria group, followed by the asymptomatic
      malaria group with the no malaria group having the least numbers. The pigmented
      neutrophil: monocyte ratio followed the same pattern. It was concluded that the
      number of pigment-containing neutrophils and the pigmented neutrophil:monocyte
      ratio may be a marker of the severity of malaria infection when one considers the
      conditions: no malaria, asymptomatic malaria and mild malaria. Further work to
      verify this hypothesis across the full spectrum of the manifestations of malaria
      infection is needed.

PMID- 9557444
TI  - Evaluation of two rapid hepatitis B surface antigen detection tests for screening
      in a blood bank.
AB  - The sensitivity and specificity of two rapid, low cost latex agglutination HBsAg
      detection tests were compared to a EIA HBsAg detection test using serum samples
      from 371 pregnant women in Kajiado, a rural Kenyan district. The sensitivity of
      the latex agglutination tests when compared to the EIA was 70.6% and 61.8%, while
      specificity was 92.0% and 85.2% respectively for the same tests. In view of their
      low sensitivity these rapid tests are not suitable for screening blood in
      district hospitals.

PMID- 9557445
TI  - Using epidemiologic tools to control an outbreak of diarrhoea in a textile
      factory, Bulawayo, Zimbabwe.
AB  - Dysentery is endemic in Zimbabwe. More than 260,000 cases and a case fatality of
      four per thousand were reported in 1993. In late July 1994, the Health Services
      Department in Bulawayo was informed of two cases of Shigella dysenteriae type I
      at a textile factory that employs 138 workers. Workers were interviewed at the
      factory regarding the date of the onset of illness, symptoms, food consumed, and
      treatment received. Factory water supply, cooking, and sanitary facilities were
      inspected. Stool and water samples were obtained for analysis. A case was defined
      as an employee presenting with diarrhoea with onset from July 24 to August 25,
      1994. Of the 99 workers on day and evening shifts, 75 (75%) were interviewed.
      Thirty eight workers met the case definition (Attack Rate 51%). Common symptoms
      were abdominal cramps (71%), and blood in stools (37%); median duration of
      diarrhoea was 11 days (range 5 to 32 days). Thirty seven (64%) of 58 workers who
      drank borehole water were ill compared to one (6%) of the 17 who did not (RR =
      10.8, 95% CI = 1.6-73). No food items consumed were significantly associated with
      the illness. Two different shigella species (2 sonnei and 2 boydii) were isolated
      from five (13%) of 38 stool specimens. Water samples from the two boreholes
      yielded numerous faecal coliforms. Neither borehole was registered as required by
      the municipal bylaws, which also forbid use of borehole water for drinking. The
      epidemiologic and laboratory evidence implicate contaminated borehole water as
      the most likely cause of this outbreak. Enforcement of municipal bylaws on
      drilling, registration and use of boreholes is essential to avoid further
      outbreaks of waterborne diseases.

PMID- 9557446
TI  - Serum calcium, phosphate and alkaline phosphate levels in epileptic children
      treated with phenobarbitone.
AB  - A longitudinal study to estimate the serum calcium, phosphate and alkaline
      phosphatase levels of 89 ambulatory epileptic children, aged between 3 years and
      12 years, and having generalised tonic-clonic seizures, was carried out. None was
      on any form of medication for the treatment of seizures prior to presentation.
      Each patient received only phenobarbitone during the period of study. Serum
      levels of the biochemical parameters were determined at presentation, 6 months
      and 12 months, while serum phenobarbitone levels were estimated at 6 months and
      12 months. Mean serum calcium, phosphate and alkaline phosphatase of the patients
      remained within the normal range. Using the paired 't' test, the differences in
      the levels of the parameters at the three measurements were not statistically
      significant (P > 0.05). Serum phenobarbitone levels remained within the
      therapeutic range during the period of study. Our results show that over a 12
      month period, serum levels of calcium, phosphate, and alkaline phosphatase,
      remain normal in ambulant epileptic children treated with phenobarbitone.

PMID- 9557447
TI  - Ethnic differences in the severity of varicella in adults in northern Saudi
      Arabia.
AB  - The severity of varicella infection in 124 expatriates from the Asian continent
      was compared to that in 120 Saudi nationals, seen in Arar Central Hospital, Arar,
      Saudi Arabia, between January 1992 and December 1994. Persistent fever (defined
      as a raised body temperature more than 37.4 degrees C lasting more than 5 days),
      extensive skin eruptions (defined as extensive, when more than 50% of the body
      surface was affected) and transient elevation of hepatic enzymes (aspartate
      transaminases > 37 U/L and alanine transaminases > 40 U/L) after excluding other
      possible causes, occurred significantly more in expatriates than in Saudis. The
      mean duration of the illness in expatriates was 15.9 +/- 3.41 days as compared to
      a mean duration of 13.1 +/- 3.52 days in Saudis. This difference was
      statistically significant (p < 0.01 Student's t-test). The findings in this study
      suggest that varicella infection runs a more severe course in expatriates from
      the Asian continent as compared to the Saudis. Treatment with the antiviral agent
      acyclovir may be indicated in this group of expatriates with varicella infection.

PMID- 9557448
TI  - Secondary bacterial infection in Ghanaian patients with scabies.
AB  - From 110 patients with secondarily infected scabies lesions, 105 bacteria
      consisting of 66 aerobes and 39 anaerobes were isolated. A mixture of aerobic and
      anaerobic bacteria was present in 15 (13.6%). The predominant aerobic and
      anaerobic bacteria were staphylococcous aureus 39.1% and pepostreptococcus spp.
      14.2% respectively. Organisms that resided in the mucus membranes close to or in
      contact with the lesions predominated in those infections. Most organisms were
      recovered from the finger and buttock lesions. These organisms were mainly staph.
      aureus, beta-haemolytic streptococci group. A and peptostreptococcus. More than
      80% of staph. aureus isolated were resistant to penicillin. Less than 20% of the
      anaerobes were resistant to penicillin. The enteric Gram-negative, E. coli and
      Klebsiella spp. showed 100% sensitivity to Amoxycilin/clavulanic acid and
      gentamicin. Pseudomonas spp. were only susceptible to gentamicin,
      Amoxycillin/clavulanic acid proved to be the most active therapeutic agent in in
      vitro against the isolated microorganisms.

PMID- 9557449
TI  - Haematological changes in human immunodeficiency virus infection. Part I: Review
      article.
AB  - This review attempts to put together the changes in the blood and bone marrow
      observed in those who are infected with human immunodeficiency virus (HIV). These
      are contribution of many published and unpublished data and experience on; blood
      counts, blood film and bone marrow films prepared and stained by MayGrunwald
      Giemsa or Leishman stain. Some changes in haemostasis are also included. The
      salient changes are cytopaenias; leucopaenia, anaemia, thrombocytopaenia, and
      bone marrow hypoplasia, although the latter occurs, it is found in a minority of
      cases. Other changes include myelodysplasia, functionally defective cells, and
      enhanced bleeding tendency particularly in those with bleeding defects. There are
      also malignancies associated with HIV infection such as Kaposi's Sarcoma and
      malignant lymphomas. The pathogenesis of these events are multi-factorial, varied
      and involve; killing of cells by the virus, syncytial formation by the cells,
      destruction of the stem cells, immune and drugs effects. These mechanisms are
      modified by factors of viral, host environment and their interactions. Changes
      are commonly found in patients with acquired immunodeficiency syndrome (AIDS) but
      can be seen in some cases anytime during the course of the disease. Once
      developed the changes are progressive. The management of these complications
      remain individualised and symptomatic. Treatment trials with the haematopoesis
      growth factors, particularly colony stimulating factors are producing some
      encouraging results. However other cytokines, for example, interleukin-6 may be
      having untoward effect such as association with the causation of Kaposi's sarcoma
      and the malignant non-Hodgkin's lymphomas. While standard approaches to the
      management of the malignancies tend to be the practice, adjustments are usually
      necessary in most patients.

PMID- 9557450
TI  - Haematological changes in human immunodeficiency virus infection. Part II.
AB  - This second part of the review looks at change seen in the bone marrow
      haemostasis and malignancies found in HIV infection. Examination of bone marrow
      is requested in the presence of cytopaenias, splenomegaly, lymphomas and
      myelodysplasia. The findings include marrow hypocellularity, myelodysplasia and
      poor marrow recovery. Dysmegakaryocytpoiesis is found in 88% while
      dyserythropoeisis in 83% of cases. Mechanisms leading to these pertubations
      include direct HIV effect on marrow progenitor cells, effect of drugs and other
      infective diseases. Altered levels and functions of growth modifies IL6 and G-CSF
      are also to contribute. Haemostatic disorder frequently noted is bleeding due to
      thrombocytopaenia. Non-Hodgkin's lymphomas with aggressive characteristics and
      Kaposi's sarcoma are the commonly associated malignancies. Currently IL6 is being
      linked with the causation of KS and NHL. While standard approaches to the
      management of these malignancies tend to be the practices, adjustments are
      usually necessary in most patients.

PMID- 9557451
TI  - Renal glycosuria treated as diabetes mellitus: case report.
AB  - A case of renal glycosuria is reported. A 55 year old female was diagnosed and
      treated in an upcountry hospital for diabetes mellitus. She developed symptoms of
      hypoglycaemia while on an oral hypoglycaemic agent, leading to her admission in
      Mulago Hospital. Persistent glycosuria was noted despite treatment and normal
      serum glucose. Oral glucose tolerance test and timed urine glucose showed a
      normal curve but high urine sugar. A diagnosis of renal glycosuria was made, oral
      hypoglycaemic therapy was stopped, patient improved and was discharged. Though
      renal glycosuria is a benign condition, mistaken diagnosis for diabetes mellitus
      puts patients at risk of hypoglycaemia due to treatment. Diagnosis of the
      condition requires physicians' awareness of its existence in our community and
      the use of Marbles' criteria obviates confusion with diabetes mellitus though it
      does not absolutely exclude Fanconi syndrome.

PMID- 9557452
TI  - Sexual abuse of minors: emerging medical and social problem in Malawi.
AB  - Sexual abuse is one of the most dehumanising human offenses. There has been an
      increasing public concern and outcry regarding the escalating wave of sexual
      abuse of young girls in Malawi, in the recent past. Four young girls, aged
      between two and seven years who were sexually abused by adult males aged between
      20 and 70 years seen and managed in the department within the past two years, are
      presented to illustrate the problem. Their physical injuries, varied reactions
      and those of their immediate families to the abuse; possible predisposing factors
      to the abuses; the related medical, psychosocial as well as legal management of
      such incidents, in the light of limited public awareness, and lack of adequately
      and appropriately trained personnel and facilities in Malawi are discussed. With
      the scare of AIDS and an increasing disintegration of the traditional family
      fabric, there is a high potential for an increase, not only of the prevalence of
      sexual abuse of minors in Malawi, but also the variety and severity of sequelae.
      It is therefore recommended that there is need to create public awareness about
      sexual abuse, train and equip the relevant personnel to appropriately manage such
      cases, as well as enact and enforce the relevant legal provisions, so as to curb
      the menace, for the well-being of the society.

PMID- 9557453
TI  - Recurrent cutaneous necrotizing vasculitis in a patient with Kikuchi's disease:
      case report.
AB  - Kikuchi's disease or histiocytic necrotizing lymphadenitis without granulocytic
      infilteration, is a clinico-pathologic entity well described in developed
      countries. We report a case of this disorder presenting with recurrent cutaneous
      necrotizing vasculitis, with the dual objective of highlighting this condition in
      developing countries and presenting an uncommon manifestation of this disorder.

PMID- 9557454
TI  - [Video laparoscopic surgery and rectal prolapse. Our experience in rectopexy].
AB  - BACKGROUND: Laparoscopy is gaining an important role in the treatment of benign
      colorectal disorders. The aim of this study is the evaluation of clinical and
      functional results in 4 patients submitted to a laparoscopy rectopexy according
      to Wells. METHODS: Four females (22-76, mean 53.7 years) affected from a total
      rectal prolapse with fecal incontinence underwent this procedure from 1993
      through 1995. Six months after surgery, at the end of a rehabilitation program
      consisting of kinesitherapy, bio-feedback and electrostimulations, all patients
      have been re-evaluated by means of a clinical exam, anorectal manometry,
      defecography. RESULTS AND CONCLUSIONS: Preliminary results seem satisfactory and
      may allow to prefer this approach instead of the traditional open one.

PMID- 9557455
TI  - [The laparoscopic approach to the polycystic liver and adnexal cysts].
AB  - Having re-examined the nosographic data acquired on the subject of hepatic
      polycystosis and uterine adnexal cysts, the authors report the results of their
      experience. On the basis of the evaluation of these results (no laparotomic
      conversion, no postoperative complications, reduced hospital stay), which are
      comparable to those reported in the literature, the authors conclude that the
      modern technology may be used to advantage in all cases where laparoscopic
      surgery is not difficult, does not require numerous tests and does not entail a
      high risk of complications.

PMID- 9557456
TI  - Does cholecystectomy always resolve biliary disease?
AB  - OBJECTIVE: To evaluate long-term effects of cholecystectomy on typical gallstone
      symptoms and associated digestive syndrome. DESIGN: Clinical prospective study on
      selected patients. SETTING: First Surgical Clinic--Catania University. SUBJECTS:
      143 gallstone patients, divided in highly symptomatic Group 1 (79) and mild
      symptomatic Group 2 (64), who underwent cholecystectomy during period 1991/92.
      MAIN OUTCOME MEASURES: 125/143 patients compiled a set questionnaire to detect
      any subjective postoperative disorders and to evaluate whether they were similar
      to preoperative symptoms or were new ones. RESULTS: 125/143 patients completed
      the 12-month follow-up programme, which revealed a 30% (38/125) with
      postcholecystectomy symptoms and 13.4% (17) with a postcholecystectomy syndrome.
      Moreover, 10% (13) of the patients reported the same digestive symptoms as before
      treatment. Statistical analysis confirmed that cholecystectomy was efficacious in
      curing gallstone related symptoms and digestive disorders in both Groups with a
      general improvement in clinical picture (p > 0.01). No significant statistical
      difference in the incidence of postcholecystectomy dyspeptic symptoms was found
      between the 2 Groups. CONCLUSION: Cholecystectomy is often efficacious in curing
      both typical gallstone related symptoms and digestive syndrome. Cholecystectomy
      patterns of failure in curing digestive disorders is unpredictable preoperatively
      on the basis of clinical features of the disease.

PMID- 9557457
TI  - [Ventrolateral hernias of the abdominal wall. The anatomicopathologic, clinical
      and therapeutic considerations].
AB  - Ventral lateral hernias of the abdominal wall are rare. On the basis of their
      location we can classify them as follows: hernias of the aponeurosis of the
      transversus muscle, hernias of the rectal sheath and transmuscular hernias of the
      iliac region. In a group of 3134 hernias of the abdominal wall observed in a
      period of 16 years, 11 ventral lateral hernias have been encountered (0.3%). The
      diagnosis often presents great difficulties as the symptoms and the clinical
      findings are not typical. They must be differentiated from hematomas of the
      rectus sheath, abscess or intra-abdominal processes. Echography and Computed
      Tomography have an important role in their detection. Nevertheless in some
      patients the true diagnosis is reached only intraoperatively. The treatment
      generally consists in surgical correction by layer closure of the fascial or
      muscular defect. In selected cases the use of prosthetic material and video
      laparoscopic repair are indicated.

PMID- 9557458
TI  - [Benign ulcers of the cecum].
AB  - Benign ulceration of the cecum is an uncommon lesion that was originally
      described by Cruveilhier in 1832. Etiology is unknown and symptomatology not
      pathognomonic. Pre-operative and intraoperative diagnosis is rare and difficult.
      Definitive diagnosis is usually obtained by histologic evaluation of the surgical
      specimen after a right hemicolectomy performed for a suspect of a neoplasm of the
      cecum. The authors present 7 cases of cecal ulcers and suggest that preoperative
      diagnosis may be due after a colonoscopy with biopsy. This examination may be
      performed only in that cases that appear without symptoms of acute abdomen. The
      authors suggest also to perform right hemicolectomy.

PMID- 9557459
TI  - [Current trends in in the treatment of spontaneous pneumothorax].
AB  - In agreement with a number of published reports we state that video thoracoscopy
      is the best means for pnx classification (Vanderschueren RJA) and for the choice
      of its treatment. Video thoracoscopy and recent innovations in video-assisted
      thoracic surgery (VATS), together produce a significant improvement in the
      results. Between February 1992 and September 1994, we treated 143 pnx in 133
      patients, 118 males, mean age 34 years (range 14-82); 5 of which undergoing a
      bilateral treatment and another 5 having to undergo a retreatment. On the basis
      of the endoscopic classification (Vanderschueren RJA), 26.1% of the cases fell
      into category I and 67.4% into the higher category, 6.5% presented enlarged
      bullous emphysema (GBE). Twenty-seven patients (20.3%), classified as category I
      at the first appearance of pnx, were treated by means of a chest tube
      thoracostomy. The remaining patients underwent surgical treatment: 106 treatments
      by VATS (74.1%) and 10 (7%) by an axillary thoracotomy. By VATS we performed: 77
      ligature/resections of bullous lesions, 9 resections of pulmonary apex, 9
      adhesiolysis, 7 GBE treatment by the "spaghetti technique", 2 coagulations of
      blebs, 1 suture and 1 parenchymal laceration repair by clips. No patients treated
      by a chest tube thoracostomy or who underwent thoracotomy presented recurrence at
      the follow-up (mean 33 months, range 15-46). We had a single complication (0.9%),
      2 treatment conversions (1.9%) and in 3 patients (2.8%) a thoracotomy was
      necessary four days later. In thoracotomy we performed 5 resections of bullous
      lesions and 2 "capitonages" were effected in those patients treated in the first
      instance; 2 parenchyma tear repairs and 1 lobectomy in those patients treated
      after the failure of VATS.

PMID- 9557460
TI  - [Meckel's diverticulum in childhood. The authors' own experience].
AB  - Meckel's diverticulum occurs in approximately 2 percent of the population and may
      present at any age. Although Meckel's diverticulum may produce an intestinal
      obstruction or perforation, simulating an appendicitis, hemorrhage is its most
      important clinical presentation. From 1989 to 1994, Meckel's diverticulum was
      discovered in ten children at laparotomy. Three cases were asymptomatic,
      representing an incidental finding at laparotomy. Of the seven symptomatic
      patients, four presented with bowel obstruction (intussusception), three had
      rectal bleeding one of whom had diverticulitis. Contrast studies--in
      gastrointestinal hemorrhage--were not helpful in establishing the diagnosis;
      colonoscopy and gastroscopy ruled out other causes of bleeding. Five of seven
      symptomatic patients had an intestinal resection while two a diverticulectomy
      after assessment that the ulcer did not require resection. No postoperative
      morbidity and mortality is reported in either groups. A Meckel's diverticulum
      found incidentally at laparotomy should be always resected as the risk of
      complication is high and that of resection low.

PMID- 9557461
TI  - Severe head trauma. Review of the factors influencing the prognosis.
AB  - A series of 72 severely head injured patients are reported, 24 (33%) with
      surgical intracranial hematomas. All patients were intensively cared for under
      the same therapeutic regime; intracranial pressure (ICP) was monitored and
      treated if increased. The series mortality was 39%. Uncontrollable increase of
      ICP (UI-ICP), always fatal, was observed in 18% of patients and in 13 of 28
      deaths (46%); the incidence of UI-ICP among deaths was higher in patients less
      than in those more than 40 years old (55% vs 25%). Patients with UI-ICP were
      frequently deeply comatose and with arterial hypotension on admission; almost all
      died in the first days. Patients directly admitted from the scene with well
      staffed Life Flight Helicopter Emergency Care compared with those directly
      admitted from the scene with different type of ambulance service (paramedics,
      police, firemen and private) had a mortality rate significantly less (20% vs 54%)
      and an incidence of UI-ICP strongly lower both among patients (5% vs 29%) and
      among deaths (25% vs 54%). Thus in this small series intensive care after
      admission was not effective to obtain good results if patients had received poor
      preadmission emergency care. Review of the literature on main clinical predictors
      of outcome in severe head injury, have made possible some observations. Ischemic
      and intracranial hypertension brain lesions were generally present in patients
      killed by head trauma; while diffuse axonal injury, frequently responsible for
      vegetative, severe disability survival and late deaths, was observed only in 20
      30% of postmortem examinations. Old age, poor neurological status and
      cardiocirculatory and respiratory disturbances prior to and upon admission
      positively worsened the outcome, while intracranial hematomas had a more variable
      predictive value. Intracranial hypertension was a definitively ominous predictor
      only if very high when the risk to be or become uncontrollable seems to be much
      elevated. UI-ICP, often fatal despite any aggressive therapy, was the single most
      frequent killer after severe head injury, responsible for about half of all
      deaths after admission. The different outcome among severe head injury series
      could be conceivably related to a different frequency of UI-ICP. Besides the
      severity of head injury and delay and mode of admission, we suggest that
      preadmission respiratory and cardiocirculatory and the quality of emergency
      medical system could strongly affect the incidence of uncontrollable increase of
      ICP in admitted patients and thus the mortality rate and favorable recovery of
      the series. The advanced preadmission emergency care service with intensive care
      after admission could significantly explain the better results often observed in
      severe head injury series.

PMID- 9557462
TI  - [Further comment on central venous catheter infections].
AB  - Many reports from the surgical literature document the incidence of catheter
      related sepsis varies between 1 and 10 per cent. In many instances sepsis is
      secondary to contamination from normal saprophyte cutaneous bacteria. In our
      Institute we set down a standardized methodology to reduce the contamination of
      venous central access from cutaneous bacteria. Of 31 patients studied, none had
      bacteria in the last 5 cm of central venous catheter, 2 had streptococcus alpha
      haemolytic colonies and coagulase negative staphylococcus colonies at the same
      time on skin over the region of venepuncture. With our paper we had attained
      one's awareness that it is very difficult to obtain zero per cent in
      contamination of central venous catheter, mainly in immunodepressed or critical
      patients, but with careful dressing and with new technology it is possible to
      reduce the contamination and following sepsis.

PMID- 9557463
TI  - [Intraoperative radiotherapy in abdominal-pelvic cancer surgery].
AB  - Intraoperative radiotherapy consists in the irradiation of the affected area,
      exposed using anesthesiological and laparotomic procedures, following the removal
      of a neoplasia using palliative or macroscopically radical surgical. This
      increases local tumour control and augments the selectivity of treatment between
      healthy and neoplastic tissues, thus obtaining a marked improvement in survival
      or palliation. The authors analyse the data reported in international literature
      regarding the possible use of intraoperative radiotherapy in patients undergoing
      abdomino-pelvic oncological surgery. The aim of the study was to evaluate this
      method for use in selected and combined treatment in which surgery represents an
      obligatory step. Studies were carried out in a few highly specialised centres
      given that special technical, logistic and professional skills were required. The
      populations studied were often very small with a marked prevalence of feasibility
      studies compared to random studies. In spite of this intraoperative radiotherapy
      is undoubtedly indicated in locally advanced gastric, rectal and vesical
      neoplasia, it represents a valid palliative solution in pancreatic neoplasia and
      in pelvic recidivation, and an effective alternative solution to mutilating
      surgery in the initial stages of vesical cancer. Positive results are obtained in
      prostate and uterine cancer, but they are reported by non-conclusive studies.
      Toxicity is acceptable and non-limiting within a given range of doses and
      irradiated volume. The "repercussion" in terms of knowledge, experience,
      scientific integration between oncological surgeons and radiotherapists is basic,
      with a marked improved in the management of cancer treatment.

PMID- 9557464
TI  - [Heredity and colorectal cancer].
AB  - The authors underline the role of inheritance in colorectal cancer and reporting
      the genealogical study of two families with high incidence of colorectal cancers
      personally observed. They thought that the genetic endowment (oncogenes,
      suppressor genes, microsatellite instability, protein-kinase C) was implicated
      directly in the genesis of disease.

PMID- 9557465
TI  - [Diverticula of the right colon. The diagnosis and treatment of complications].
AB  - BACKGROUND: Diverticula are localized in the right colon with a rate of 6.7-14%
      in Western countries. Two types of diverticula have been described in the right
      colon, on the basis of etiologic and pathological features: multiple diverticula
      and solitary diverticulum of the caecum. The most common clinical presentation of
      the right-sided colonic diverticula is an acute inflammatory complication, which
      is difficult to distinguish from other causes of right iliac fossa pain. METHODS:
      A survey of the literature is presented and personal experience relative to 4
      cases of acute diverticulitis of the right colon observed over a 10-year period
      is described. RESULTS: In all the patients the preoperative diagnosis was acute
      appendicitis. In two cases the poor clinical conditions of the patients were
      associated with the free perforation of a solitary caecal diverticulum and
      diffuse faecal peritonitis. A temporary caecostomy was therefore required. In two
      cases a localized inflammatory mass was found around a perforated solitary
      diverticulum of the caecum. An ileocaecal resection was performed. CONCLUSIONS:
      The purpose of this study is to emphasize the epidemiological, etiologic and
      clinical features of right-sided colonic diverticula, and the diagnostic and
      therapeutic management of their complications.

PMID- 9557466
TI  - [Gastric leiomyoblastoma. Its preoperative diagnosis by echo-guided needle
      aspiration. A report of 2 clinical cases].
AB  - The authors report two cases of gastric leiomyoblastoma, one benign and one
      malignant, come to clinical observation for digestive hemorrhage; in both cases a
      preoperating diagnosis of benignity or malignity was made and in one case even of
      histotype, thanks to fine needle biopsy. After a short introduction regarding
      some historical notes, the predictive parameters of malignity, the classification
      of this rare myoid tumor, the authors discuss the distribution of the pathology
      in the population, the symptomatology, the diagnostic "iter" with particular
      regard to the needle biopsy, the surgical treatment, and the indispensable
      parameters for formulating a correct prognosis.

PMID- 9557467
TI  - [The ingestion of foreign bodies for the purpose of self-injury. The conservative
      treatment of 2 clinical cases].
AB  - Although not rare, the ingestion of foreign bodies becomes uncommon when it is
      done with intent to cause self-damage. When used for this purpose, foreign bodies
      usually take the form of liquid substances, such as caustic agents, detergents,
      poisons, etc. It is less rare in certain situations like psychiatric and prison
      settings. The author reports two cases of foreign bodies voluntarily swallowed by
      patients in prison.

PMID- 9557468
TI  - [Bilateral adrenal lymphoma. A case report].
AB  - A rare case of malignant non-Hodgkin lymphoma of the adrenal gland in a 59-year
      old male is reported. This patient, completely healthy, observed for a routine
      check after a laparoscopic cholecystectomy performed one year before, underwent
      an explorative laparatomy for getting information about a retroperitoneal mass,
      ultrasound scan observed. A CT guided needle biopsy was inconclusive to clarify
      this rare haematological diagnosis.

PMID- 9557469
TI  - [The utility of isolating the recurrent nerve and parathyroids in the prevention
      of complications in thyroid surgery. The role of the superior laryngeal nerve and
      C cells].
AB  - The authors emphasize systematic isolation of the recurrent nerve and of the
      parathyroids, to prevent complications in surgery of the thyroid. Moreover they
      try to underline the significance of the superior laryngeal nerve and the role of
      parafollicular cells (today unknown) for a rational and modern therapy of the non
      neoplastic diseases of the thyroid.

PMID- 9557470
TI  - [The use of the BAR-Valtrac-type pressure stapler in surgery of the large
      intestine].
AB  - A total of 148 patients underwent colon resection between June 1993 and November
      1994 at the General Surgery Division of Busto Arsizio Hospital; anastomosis was
      performed using BAR Valtrac in 58 patients (39%), namely 28 males and 30 women
      with a mean age of 66.3 years. Surgery was elective in 90% of cases and in 84% of
      patients was secondary to neoplastic pathologies. Recanalisation occurred within
      a mean of 5.5 days after surgery, whereas the average hospital stay was 14.4
      days. The authors report the absence of mortality and the low morbidity levels
      connected to the use of this anastomotic technique. Emphasis is also laid on the
      absence of anastomotic stenosis in all endoscopic controls performed to date.

PMID- 9557471
TI  - [Pefloxacin versus ceftriaxone in single-dose antibiotic prophylaxis in general
      clean-contaminated surgery. The Pefloxacin Study Group].
AB  - Single-shot surgical prophylaxis is today used in all clean-contaminated surgery,
      because it is able to reduce the incidence of post-surgical infections. The aim
      of this clinical trial is to evaluate the efficacy of Pefloxacin 800 mg i.v. slow
      infusion in single administration 1-2 hours before surgery versus ceftriaxone 2 g
      i.v. 1-2 hours before surgery in 297 patients suffering from clean-contaminated
      surgery, especially biliary surgery and gastrectomy. Efficacy of prophylaxis in
      259 patients, evaluable according to the protocol, was evaluated in terms of
      appearance of post-surgical infections (urinary, respiratory and wound
      infections). In the Pefloxacin group (128 patients), no cases of wound infections
      were observed, except one case of wound sterile secretion, without dehiscence,
      (0.81%), one case of urinary infection (0.81%) and three cases of respiratory
      infections (2.34%). In the ceftriaxone group (131 patients), three cases of wound
      sterile secretion without dehiscence (2.36%), one case of urinary infections
      (0.76%) and four cases of respiratory infections (3.05%) were observed. From this
      study we can conclude that single-shot surgical prophylaxis with pefloxacin, drug
      with microbiological and pharmacokinetics characteristics suitable for
      prophylaxis, is able to prevent postsurgical nosocomial infections as well as
      ceftriaxone, considered a reference drug largely used in this indication.

PMID- 9557472
TI  - [Echography at "high resolution" in the diagnosis of cervical lymphadenopathies
      in follow-up of thyroid carcinoma].
AB  - BACKGROUND: In the diagnosis and follow-up of differentiated thyroid cancer (DTC)
      patients, a major clinical objective is to differentiate whether the cause of
      enlarged neck lymph nodes is either tumorous or inflammatory. High-frequency (7.5
      10 MHz) ultrasound examination proved to be highly informative in this regard. An
      oval shape of the examined lymph node (longitudinal/anteroposterior diameter
      ratio, L/A > 1.5) and a central echogenic hilus indicate a benign
      lymphadenopathy. Roundness (L/A < or = 1.5), absence of the central echogenic
      hilus and a parenchymatous echogenicity are considered as signs of malignancy.
      METHODS: A series of 131 lymph nodes in DTC patients were examined at ultrasound
      and, on the basis of round shape (L/A < or = 1.5) in association with either one
      or both the other features (absence of central echogenic hilus, homogenous
      internal echo), 94 lymph nodes were classified a "malignant" and 37 "benign". The
      ultrasonographic diagnosis was evaluated with either cytologic or histologic
      diagnosis in all "malignant" nodes and in 7/30 "benign" nodes. In the other 30
      "benign" nodes volume shrinkage or lymph node disappearance was observed during
      follow-up period. RESULTS: According to the results obtained, the ultrasound
      features utilized provided a good diagnostic accuracy (87%) with only 5 false
      positive case. CONCLUSIONS: High-frequency sonography, therefore, must be
      considered a useful and accurate method for evaluating suspected lymphadenopathy
      in DTC patients.

PMID- 9557473
TI  - [HIV infection and the endocrine system in children].
AB  - HIV infected children characteristically develop a failure to thrive in 25% to
      100% of symptomatic cases, with a significantly reduced survival time. The
      pathogenic mechanism for HIV-driven failure to thrive is not yet understood.
      Likely it is multifactorial, endocrine dysregulation surely plays a major, even
      if not yet fully clarified, role in this complication. Global evaluation of
      endocrine data could allow to better understand the mechanisms underlying the
      failure to thrive in HIV-infected children, also in relationship with the current
      manifestations of the HIV infection. The results of the endocrine studies could
      also be related with additional features of the children, as their immunological
      status. It is well known that endocrine and immune functions are closely related
      in animals and in humans. Thus, the evaluation of the results of studies could
      provide some interesting information about the relationships between them in the
      HIV-infected child. Such relationships, if present, also could help to better
      define therapeutic interventions in these children.

PMID- 9557474
TI  - [Agenesis of the thyroid lobe associated with Hashimoto's thyroiditis].
AB  - A thyroid hemiagenesis in association with Hashimoto's thyroiditis and mild
      hypofunction in a 40 years woman, is described. It is an unusual association. The
      clinical, hormonal, immunological, instrumental and cytological diagnosis has
      been established. The importance of the scintigraphic pattern and the
      differential diagnosis with other pathological situations, such as Plummer's
      disease and several destroying processes, is emphasized. It is suggested that
      thyroid hemiagenesis has not to be regarded as clinically insignificant, in
      consideration of a possible association with pathologies of the normally
      developed lobe (Graves' disease, myxoedema, goiter, Hashimoto's thyroiditis, and
      especially neoplastic degeneration) or with nonthyroid diseases
      (hyperparathyroidism).

PMID- 9557475
TI  - [Hyperfunctioning thyroid carcinoma. Description of a case].
AB  - Differentiated thyroid cancers account for 1% of all neoplasias but only for 2.3%
      of thyroid nodules. A particular condition is represented by the association with
      hyperthyroidism, which is found in about 7% of cases. Even more rarely may be
      themselves cause of thyrotoxicosis. In the present paper, the case of a 66-year
      old male patient, bearing a recently appeared goiter, referred to us for
      suspicion of lung cancer and hyperthyroid symptoms, is reported. Among
      appropriate investigations, the finding of high titer of thyroglobulin in the
      aspiration needle and cytology examination suggested that thyroid lesion was
      primary and not metastatic, while scintiscan with J-131 isotope showed that
      excess of thyroid hormones was just due to it; histological diagnosis was of
      papillary carcinoma. As to the pathogenesis of the neoplasma during
      hyperthyroidism, a causal role of thyroid stimulating auto-antibodies has been
      suggested in the cases associated with Graves' disease, absent in our patient,
      which could elicitate cancer progression in the mean time. Interestingly,
      activating mutation of thyroid hormone receptor (TSH-r) gene has been
      demonstrated in a hyperfunctioning differentiated cancer. Notwithstanding the
      unexpected clinical behaviour may appear very rare, molecular biology studies on
      aspiration biopsies (FNAB) will allow, in the future, to better define the
      neoplastic nature of some hot nodules. In personal opinion, this particular
      pathology must be attently searched both for its implications in the prognosis
      and therapeutic strategy and because it could be less rare than generally
      considered up to now.

PMID- 9557476
TI  - Toxic nodular goiter and thymic hyperplasia in an adult. Case report.

PMID- 9557477
TI  - [The diagnosis of thyroid nodules].

PMID- 9557478
TI  - [Echographic markers of fetal chromosomopathies. Diagnostic possibilities with
      transvaginal ultrasonography and our experience].
AB  - OBJECTIVE: Aim of this study was to evaluate, during early pregnancy, the
      correlation of some anomalies and malformations with fetal chromosomopathies.
      EXPERIMENTAL DESIGN: Morphostructural and biometric anomalies in chromosomopathic
      fetuses were evaluated. PATIENTS: 1331 pregnancies at high risk for genetic
      disease and malformations referred to our center for prenatal diagnosis. METHOD:
      Scans were performed using endovaginal convex probes (5.0 to 7.0 MHz). SURVEYS:
      Urinary, cardiac and cerebral malformations as well as alterations of bone growth
      were evaluated. RESULTS: With respect to the other malformations, cystic hygroma
      is more frequently associated with an abnormal fetal karyotype. CONCLUSIONS: The
      majority of morphostructural abnormalities diagnosed during first trimester by
      transvaginal sonography cannot, in according to personal experience, be used as
      markers of chromosomopathies.

PMID- 9557479
TI  - [Changes in fetal karyotype in non-immune hydrops fetalis].
AB  - BACKGROUND AND METHODS: Among the pregnant patients who underwent an
      amniocentesis at our department of prenatal diagnosis (Division of Gynecology and
      Obstetrics of the University "Federico II" in Naples) from 1989 to 1996, 16
      patients were affected by non-immune hydrops faetalis associated with chromosomal
      diseases. RESULTS: The karyotype test revealed at an ultrasound exam of the fetus
      that 11 cases were affected by trisomy 21, 4 cases by Turner syndrome and one
      case by trisomy 18. This study took into consideration all the pathogenetic
      factors and the diagnostic problems of non-immune hydrops faetalis in fetus
      affected by associated chromosomal associated anomalies. CONCLUSIONS: Since the
      incidence of the chromosomal anomalies on fetus affected by non-immune hydrops
      foetal is was very high, there was the necessity to carry out a routine karyotype
      test if the ultrasonography revealed anomalies of the hydrops, during the first
      three months of pregnancy.

PMID- 9557480
TI  - [Early prognostic ultrasonographic indices in pregnancy with fetal cystic
      hygroma].
AB  - OBJECTIVE: Aim of this study was the correlation of same early ultrasonographic
      signs with fetal karyotype, prognosis of pregnancy and neonatal outcome.
      EXPERIMENTAL DESIGN: Volume of cystic hygroma and presence of septations are
      correlated with fetal karyotype and an ultrasonographic follow-up was carried out
      during pregnancy. Details concerning neonatal outcome were recorded at delivery.
      PATIENTS: Diagnosis was performed in 13 patients between 8.3 to 16.5 weeks'
      gestation referred to our center for prenatal diagnosis or for obstetric reasons.
      METHOD: Ultrasonographic examinations were performed using 5.0 and 6.0 MHz
      endovaginal convex probes. SURVEYS: Hygroma was diagnosed as a cystic dilatation
      in the nuchal region larger than 3 mm in diameter in the anterolateral aspects.
      The volume was calculated considering the lesion as spherical and using the
      standard formula for an ellipsoid volume; the presence of septations was
      considered. RESULTS: A volume greater than 70 cc3 and the presence of septations
      demonstrated a strictly correlation with fetal karyotype, evolution of the
      features, pregnancy and neonatal outcome. CONCLUSIONS: Prognosis varies depending
      on fetal karyotype, volume, presence of septations and other associated
      malformations. The volume of the hygroma and the presence of septa are associated
      with higher incidence of chromosomal diseases and a poorer fetal prognosis.

PMID- 9557481
TI  - [Preliminary diagnostic evaluation of submucosal myoma using operative
      hysteroscopy].
AB  - BACKGROUND AND AIM: The authors aim to underline the importance of preliminary
      diagnostic evaluation in the treatment of submucous leiomyoma using hysteroscopy.
      MATERIALS AND METHODS: The study examined 18 patients monitored at the Institute
      of Obstetrics and Gynecology of "La Sapienza" University of Rome between January
      and December 1995 in whom it was possible to make a correct definition of the
      lesion to be treated (number, site, size, etc.) using 3 different diagnostic
      methods: hysteroscopy (HS), transvaginal scan (TSV) and transvaginal
      echohysterography (TVHS) The authors focused attention on three different
      parameters: leiomyoma size, extension (intracavity/intramural portion) and
      evaluation of the residual leiomyoma, which are essential for optimal endoscopic
      resection. RESULTS: HS enabled the number, size, site, origin, base, submucous
      portion and relations with tube operings to be evaluated, but did not allow the
      myometrial part of the lesion to be examined. CONCLUSIONS: Integration with TSV,
      even if this does not allow a precise definition of the extension, highlights the
      size, site, involvement of myometrial structure and relations with the
      perimetrium, thus allowing the possibility of evaluating the residual myometrium.
      Compared to the above methods, TVHS highlights the effective extension (namely
      the submucous/intramural portion) and localization of the neoformation.

PMID- 9557482
TI  - [Sexual activity, cardiotocographic findings and time of delivery in physiologic
      pregnancy. Survey of a population controlled by ambulatory cardiotocography].
AB  - STUDY DESIGN: Out of 720 patients with physiological pregnancy coming weekly to
      the cardiotocography service, it was decided to verify if, in comparison with
      controls, sexual activity after the 37th week, might make some differences as
      regard to duration of pregnancy, incidence of PROM and cesarean section. RESULTS:
      Only a small minority was sexually active. From statistical tests it was observed
      that sexual intercourse coincided with a greater parity, a lower maternal age, a
      greater number of nonstress test with uterine contractions and an average
      duration of pregnancy, slightly lower than in controls (38.80 vs 39.76 weeks).
      Most of the pregnancies over the 40th week and the greatest incidence of cesarean
      sections due to fetal distress were observed in sexually inactive patients. A
      sexual activity after the 37th week did not indicate a greater incidence of PROM
      CONCLUSIONS: According to personal opinion and provided there is not an obstetric
      pathology, there are advantages and not disadvantages from a less prohibitionist
      habit concerning sex by the end of the period of pregnancy.

PMID- 9557483
TI  - [Delivery at the Institute for Gynecology and Obstetrics of the Messina
      University Polyclinic. Comparison of two periods].
AB  - BACKGROUND: Delivery methods and current pregnancy monitoring, comparing the last
      twenty-years in the light of new medical and diagnostic findings are presented.
      METHODS AND RESULTS: Moreover, examining carefully vaginal and laparotomic
      delivery it is to be noticed that a more careful wait can increase spontaneous
      deliveries, with the due exceptions, so that the rate of cesarean section is
      established on current values. CONCLUSIONS: At last it is to be hoped that
      maternal mortality and morbility decrease and particularly fetal mortality so as
      to guarantee a future devoid of psychophysic handicaps to newborn infants.

PMID- 9557484
TI  - Contraception in diabetic women.
AB  - There is a very strong need for an effective and reliable method of contraception
      in the diabetic woman. An unplanned pregnancy that occurs when her diabetes is
      not under good control can have disastrous consequences, ranging from abortion to
      a congenitally malformed fetus. The most important factor in the contraceptive
      decision for the diabetic patient, especially the IDDM patient, is that the
      choice be made not by the clinician alone or the patient alone, but through a
      carefully through-out process that involves both patient and physician.

PMID- 9557485
TI  - [Simultaneous intrauterine and tubal pregnancy. A clinical case].
AB  - The presence at the same time of intrauterine and ectopic (heterotopic) pregnancy
      is unusual. A case of acute abdomen by tubaric haemorrage in a patient with
      ectopic pregnancy and evolutive intrauterine pregnancy during first trimester is
      reported. After surgical therapy, the intrauterine pregnancy had a good
      evolution.

PMID- 9557486
TI  - [Treatment of endometriosis with GnRH analogues].
AB  - BACKGROUND: Since a continuous administration of adequate doses of luteinizing
      hormone-releasing hormones (LHRH) or of an agonist leads to a hypogonadism-like
      condition, it is possible to use this effect for the treatment of endometriosis.
      The present study reports the results obtained in the Gynaecology and Obstetrics
      Institute of the Second University of Naples, with a long-acting formulation of a
      GnRH analogues (D-Trp6-LHRH) in biodegradable microcapsules, at monthly
      intervals. MATERIALS AND METHODS: The study was carried out on 40 women with
      endometriosis diagnosed by laparoscopy or laparotomy. The duration of treatment
      in patients in stage I-II was of 6 months, in patients in stage III or IV was of
      9 months. RESULTS: After 12 months from the end of therapy, 27 patients did not
      show any sign of endometriosis with ultrasound and clinical examination; 13
      patients still showing endometriosis were from III or IV stage. CONCLUSIONS: This
      long-acting formulation should offer a better approach for chronic treatment.

PMID- 9557487
TI  - [Evaluation of hemoglobin and hematocrit in pregnant women receiving folate and
      iron supplements].
AB  - BACKGROUND AND AIMS: From week 8 there is a reduction in hemoglobin and
      hematocrit (owing to the increased plasma volume which exceeds the increased
      erythrocytic content) that continues to fall steadily until week 16-22,
      flattening out at a level of 10-11 g/100 ml for hemoglobin and 32-34% for
      hematocrit. Bone marrow produces red blood cells and hemoglobin in proportion to
      the increase in plasma volume, provided that there is an adequate iron supply
      (higher in pregnancy compared to the usual dietary intake). For this reason, the
      authors examined the systematic supplementation of pregnant women with ferrous
      gluconate and folic acid, another important element for numerous metabolic
      reactions which is also lacking in pregnancy owing to increased requirements.
      METHODS: The study showed that pregnant patients receiving folic acid and iron
      supplements from week 5 to 40 presented hematocrit readings and hemoglobin levels
      from week 12 that were constantly higher compared to the population not receiving
      supplements, with statistically significant and highly significant differences
      respectively. The few collateral effects observed in a limited group of patients
      allow the authors to define the tolerability of the proposed treatment as
      "excellent". They emphasise, however, the importance of constant supplementation
      with folic acid and iron throughout pregnancy to avoid sideropenic anemia, with
      considerable benefits in terms of the physical conditions of the pregnant woman,
      the supply of O2 to the villi, fetal wellbeing and the need to resort to possible
      blood transfusions in the event of major blood losses at birth.

PMID- 9557488
TI  - [Use of arginine in intruterine growth retardation (IUGR). Authors' experience].
AB  - BACKGROUND: Asymmetrical intrauterine growth retardation (IUGR) represents a
      foetal mechanism, consequent to placental insufficiency, due to many factors:
      genetic, vascular, malformative. At present, no therapy is really efficient. The
      aim of this study was to evaluate the efficacy, in these pathological conditions,
      of the use of L-arginine. This amino-acid improves GH-RH incretion, with
      consequent increase of plasmatic GH influencing somatic growth. L-arginine
      moreover, is the obligatory precursor for nitric oxide (NO) enzymatic synthesis
      (Endothelial-derived relaxing factor). NO helps the prolapse of smooth
      musculature and, consequently, the improvement of placental blood circulation.
      METHODS: On the basis of the double activity of NO, vasodilatation and GH-RH
      induction, 43 pregnant women have been treated suffering from IUGR, diagnosed by
      ultrasonic examination an by evaluation of Doppler velocimetry values, from 30th
      week of gestation, administering L-arginine (Bioarginina, 6 g per os/day).
      Periodically, USG and Doppler velocimetry examinations were performed to evalue
      foetal growth and possible increase of peripheral vessels resistance. RESULTS: 32
      patients improved the clinical course of pregnancy: 19 recovered the whole
      retardation; 9 only one week; 4 had premature delivery after 36 weeks with foetal
      weight coincident with gestational age. CONCLUSIONS: The positive results suggest
      the prosecution of clinical studies in order to attempt the achievement of an
      effective pharmacological treatment of IUGR.

PMID- 9557489
TI  - [Mitochondrial DNA and pediatric illness].

PMID- 9557490
TI  - [Congenital dysplasia of the hip in children of immigrants from developing
      countries].
AB  - BACKGROUND: Aim of study was to ascertain the possible presence of congenital
      dysplasia of the hip in infants (CDH) in the population immigrated from countries
      where the problem is surely neglected from the local health service and estimate
      its incidence. Moreover to observe the impact of the CDH problem on the parents
      of these children, sometimes of scarce culture or rather of scarce comprehension
      of the language. Finally, to verify the answer of parents to the medical
      prescriptions and to the not simple therapeutic formality. METHODS: From 1989 to
      1996, the hip has been examined by Graf ultrasounds (US) method on a population
      of 181 infants born from developing countries' immigrants in Italy; 77 of them
      were Egyptians. RESULTS: Even if the density of the population studied was not
      very high, the results presented in this paper are innovative and differ from the
      literature on this matter. Among the 362 hips examined with US, only 5 hips were
      found to be pathologic (4 Egyptians and 1 Philippine; 2 type uD and 3 type IIC of
      Graf), and they were treated and recovered with a harm in about 3 months.
      CONCLUSIONS: This work underlines the necessity that all immigrated infants
      should be studied with US hip exams and that CDH in these people should not be
      under-evaluated: the very low occurrence of this pathology in developing
      countries is probably mainly due to scarsity of studies on this matter. This
      allows not only to avoid hip dislocation in these subjects, but also to the
      society to avoid the necessary cost of the subsequent treatment of well more
      serious diseases such as osteoarthritis of the hip on dysplastic basis, in
      subjects that likely will stay in our country definitely, becoming Italian
      citizens to all effects.

PMID- 9557491
TI  - [Results of periumbilical approach to hypertrophic pyloric stenosis treatment.
      Personal experience].
AB  - BACKGROUND: Ramstedt's pyloromyotomy is the universally accepted treatment for
      hypertrophic pyloric stenosis. It could be performed through different surgical
      approaches: Robertson muscle splitting incision, transverse right transrectal
      incision, median longitudinal incision laparoscopic approach and circumumbilical
      incision. METHODS: This latter technique was successfully personally utilized for
      the treatment of 33 consecutive patients; 29 patient were male and 4 female, age
      ranged from 15 to 52 days (median value 32.6 days), previously full term, normal
      weighing newborns. In all patients but one, the large pyloric mass bulged through
      the incision and the Ramstedt's pyloromyotomy was performed as usual. In one
      case, the pyloromyotomy has been done through the incision by holding the large
      pylorus firmly beneath the abdominal wall. The operative time has been quite
      similar to that obtained with the transverse right incision. The mean
      hospitalization period has been of four days. RESULTS: No operative or
      postoperative complications were observed. Particularly, despite no antibiotics
      were used, no wounds infections occurred. CONCLUSIONS: The esthetic result was
      satisfying in all cases after one month follow-up.

PMID- 9557492
TI  - Lactose, oligosaccharide and monosaccharide content of milk from mothers
      delivering preterm newborns over the first month of lactation.
AB  - BACKGROUND: Monosaccharide, lactose and oligosaccharide content of milk from
      mothers delivering prematurely (PT milk) was studied to evaluate whether changes
      occur during lactation, as observed in milk from mothers delivering at term (T
      milk). METHODS: To study a homogeneous population, women having the most common
      phenotype (secretory both Lewis and A, B, or H phenotype) were selected. Milk
      samples from 26 mothers who delivered between the 27th and 35th week of gestation
      were collected at the 4th, 10th, and 30th post-partum days. Monosaccharides,
      lactose and oligosaccharides were measured by high-pressure liquid
      chromatography. RESULTS: Lactose concentration increased significantly (p < 0.05)
      from 52.81 +/- 8.2 g/L on day 4 to 69.24 +/- 9.36 g/L on day 30. During the same
      period of time oligosaccharide content decreased significantly (p < 0.05) from
      25.61 +/- 5.19 g/L to 15.83 +/- 6.05 g/L. Monosaccharides did not show
      statistically significant variations. CONCLUSIONS: Our results indicate that PT
      milk contains in addition to lactose, a substantial amount of oligosaccharides
      and a lower percentage of monosaccharides. Compared to T milk, in the colostral
      phase PT milk presents significantly lower lactose concentration (p < 0.0001); on
      the contrary its oligosaccharide content is significantly higher (p < 0.0001).
      The physiological role of human milk carbohydrates in view of the peculiar needs
      of the preterm newborn is also discussed.

PMID- 9557493
TI  - [From atopic dermatitis to asthma].
AB  - Atopic dermatitis (AD) is the most common chronic skin disorder in infancy and
      childhood and is the main hallmark of atopic constitution. The disease is
      multifactorial, and although genetic predisposition is certainly a prerequisite,
      a number of environmental factors modulate the phenotypic expression of AD. The
      majority of affected children shows IgE sensitisation towards a large variety of
      foods and aeroallergens. Since at least 1600, it has been recognized that
      patients with AD have a high predisposition to develop asthma. Recent
      epidemiological studies show that AD is commonly seen in individuals from
      families with a history of asthma. In addition, in population where asthma is
      uncommon, AD is also uncommon. The sex distribution of AD and asthma is the same,
      with boys affected significantly more often by these two atopic diseases and in
      similar proportions. The ETAC project (Early Treatment of the Atopic Child) is a
      large multicenter, multi-national, double blind, placebo controlled, randomised
      trial. The main objective of the study is to stop the progression from AD to
      asthma in young children with AD using early therapeutic intervention with
      Cetirizine and the second objective is to investigate the main risk factors for
      the onset of asthma. The results of this study indicate that exposure to potent
      allergens such as cat or mite significantly increased the risk of sensitisation
      to these allergens. Prolonged breast feeding was associated with a lowest
      sensitisation rate to cow milk proteins and to egg. Therefore environmental
      factors seem to play a crucial role in IgE sensitisation in children with AD.

PMID- 9557494
TI  - [Diabetes, hypothyroidism and celiac disease in Down's syndrome. A case report].
AB  - It is well known that Down's syndrome patients frequently suffer from immune
      system diseases leading to the production of autoantibodies and the onset of
      correlated pathologies. These disorders become increasingly frequent as the
      patients grow older and the onset of one autoimmune disease often predisposes the
      development of others. Autoimmune thyroiditis is the most frequent disorder and
      appears to affect 39% of adult patients. Over the past years a number of reports
      have been published regarding the coexistence of various autoimmune diseases in
      DS patients, but little is still known about the relationship between these
      pathologies and celiac disease. In order to contribute to knowledge regarding the
      prevalence of this association, the authors report a case of a DS patient who
      developed diabetes mellitus, hypothyroidism and celiac disease at different
      times. This case provides further confirmation of the association between Down's
      syndrome and autoimmune pathologies. The authors feel that follow-up programmes
      for DS patients should include an evaluation of thyroid function and antithyroid
      antibodies given that the onset of glandular hypofunction may be very subtle.
      Furthermore, they should also include tests to assay glycemia, anti-pancreatic
      insula and anti-insulin antibodies for diabetes and AGA and EMA for celiac
      disease.

PMID- 9557495
TI  - [Medical and surgical therapy of familial hypophosphatemic vitamin D resistant
      rickets with ambulation disorders].
AB  - Three children with familial hypophosphatemic rickets showed, in the untreated
      state, active rickets of the metaphyseal areas of long bones. All were treated
      with combined phosphate /1-2 g daily by mouth in 4-5 divided doses) and vitamin
      D2 therapy for 2-5 years. The radiological appearance of the metaphyses became
      practically normal in two, whereas little change took place in the endosteal bone
      surface. Bone biopsies demonstrated osteomalacia. Therefore, two subjects were
      given phospate (1-2 g daily) and 1-alpha-hydroxyvitamin D (0.25-0.50 microgram
      daily) for 2 years; then phosphate (1 g daily) and 1.25 dihydroxyvitamin D (0.25
      0.50 microgram daily) combined therapy for 5 years; the third patient had
      phosphate (1 g daily) and 1.25 dihydroxyvitamin D (0.25 microgram daily) combined
      therapy for 2 years. After therapy with low doses of 1.25 dihydroxyvitamin D, X
      rays showed a nearly normal bone aspect, without nephrocalcinosis in all
      patients. All subjects were submitted to osteothomies with positive results.

PMID- 9557496
TI  - Anaesthetic management of children with type II and III Gaucher disease.
AB  - The anaesthetic management of two children with Gaucher disease is described. The
      cases were a girl aged 12 and a boy aged 4 who had undergone 13 and 3 anaesthetic
      interventions respectively for endoscopic, orthopaedic, general, otolaryngologic
      and dental surgical procedures over a total period of 11 years. Anaesthetic
      management of these patients can be achieved with various agents and techniques,
      but care is needed to identify preoperative end-organ dysfunction and prevent
      postoperative respiratory insufficiency. In particular, regional anaesthesia,
      when suitable, has certain advantages that have made it a worthwhile alternative
      to general anaesthesia.

PMID- 9557497
TI  - [A case report of reversible biliary pseudolithiasis caused by ceftriaxone in
      childhood: does the problem deserve greater attention?].
AB  - The authors report the case of a nine-year-old girl admitted to hospital with
      signs of meningeal irritation during the course of hyperpyretic phlogosis of the
      upper airways who presented, after 6 days' treatment with CFTX, at a dose of 50
      mg/kg/day (1.5 g/day), therefore at the maximum recommended dose for the
      antibiotic in question, symptomatic cholecystic "pseudolithiasis" which resolved
      two weeks after the suspension of the drug. This case appears to concord with
      recent reports of "pseudolithiasis" in childhood that appeared with doses not
      regarded as being at risk, and it draws attention to the etiopathogenetic
      importance of other factors, including familial recurrence. The authors recommend
      a reasonable use of CFTX and the need to be "vigilant" both in relation to the
      onset and evolution of the clinical condition described above.

PMID- 9557498
TI  - [Volocimetric evaluation of spermatic vessels with echo color doppler in patients
      with idiopathic varicocele].
AB  - BACKGROUND AND AIMS: There is a high incidence of varicocele or dilatation of the
      spermatic vessels associated with reflux in the male population varying,
      according to statistics, from 4.5 to 30.7%. Among the numerous hypotheses put
      forward to explain infertility in approximately 50% of patients with varicocele,
      it has recently been shown that there is an increased concentration of
      noradrenalin in the spermatic vessel which might be responsible for chronic
      arterial vasoconstriction affecting the gonads, leading to endothelial
      hyperplasia and consequent infertility. MATERIALS AND METHODS: In this study the
      authors have evaluated the bilateral flow of spermatic arteries at the level of
      the scrotum in patients with varicocele and in the healthy (varicocele-free)
      population with normal and hypospermatogenesis. RESULTS: In all groups and in the
      absence of other major pathologies (including arterial hypertension), no
      significant differences were found in systolic peak velocity (SPV) in relation to
      the presence or otherwise of varicocele and the degree of reflux. Mean SPV ranged
      between 3.5 and 4 cm/sec in patients with hypo- and/or normal zoospermia both in
      the varicocele and healthy population. CONCLUSIONS: In line with other authors,
      we feel that despite the lack of substantial differences in arterial flow in the
      patients examined, it is not possible at present to explore the testicular
      microcirculation and possible hypoperfusion using eco color-Doppler, in spite of
      the fact that the method shows a high level of diagnostic accuracy in the
      diagnosis of phlogistic pathologies and/or twisting of the spermatic cord. New
      approaches might be provided through the improved study of the microcirculation
      using power Doppler which appears to be more sensitive than eco color-Doppler in
      visualizing small intraparenchymal vessels.

PMID- 9557499
TI  - [Major renal trauma. Therapeutic approaches and our experience].
AB  - METHODS: During a 12-year period, 110 patients with renal blunt trauma have been
      observed. Renal exploration was performed in 17 patients (15.45%). Absolute
      indications for exploration were bleeding and pulsatile perirenal hematoma and
      associated abdominal injuries. Salvage was successful in 76.48% of the kidneys
      explored and hemostatic nephrectomy was required in 23.52%. The success rate was
      based on early vascular control and reconstructive techniques of renorrhaphy,
      partial nephrectomy and coverage with omental pedicle flaps. RESULTS: At follow
      up, hypertension occurred in only 3 patients and resolved spontaneously after 3-6
      months. CONCLUSIONS: On the basis of personal experience, the conclusion is drawn
      in that when renal exploration is required, reconstruction can be successful in a
      high percentage of patients.

PMID- 9557500
TI  - [Protein and amino acid metabolism in chronic renal failure].
AB  - Some degrees of protein deficiency, suggestive of abnormal protein metabolism,
      are a well-known feature of chronic renal failure (CRF). Serum albumin
      concentration, an index of malnutrition and deranged protein metabolism, is
      frequently decreased relatively early in CRF, even in absence of heavy
      proteinuria: a more subtle but characteristic abnormality is found in the plasma
      profile of amino acids. In addition, there is an accumulation in the plasma and
      tissues of many products of protein metabolism; some of these have been
      considered as uremic toxins, while others are largely undefined. The origin of
      abnormalities in protein metabolism are multifactorial. The defect are caused at
      least partly by dietary deficiency, as well as by the inability of the failing
      kidney to excrete normal end products of nitrogen and protein metabolism and by
      the effect of altered uremic milieu on overall metabolism.

PMID- 9557501
TI  - [Unusual development of urothelioma of the upper urinary tract].
AB  - A case of extrarenal spreading of transitional cell carcinoma caused by rupture
      of ureterohydronephrosis by ureteral transitional cell carcinoma is reported.
      Ultrasonography and CT revealed the presence of a severe right
      ureterohydronephrosis with large septa and a 2 cm diameter exophytic neoplasia of
      the middle ureter. Nephroureterectomy was performed with excision of a perirenal
      mass. Histologic examination revealed the presence of transitional cell carcinoma
      in the perirenal mass, caused by dissemination after renal rupture. CT and
      ultrasonography were not able to differentiate hydronephrosis from pericapsular
      spreading because of the extreme disruption of the renal parenchyma.

PMID- 9557502
TI  - [Major complications of percutaneous nephrolithotripsy (PCNL). Analysis of our
      cases].
AB  - The major complications occurred in 140 cases of percutaneous nephrolithotomy,
      from March 1988 to December 1996 are studied. They were: 1 important hemorrhage
      with secondary nephrectomy, 1 intestinal fistula resolved with parenteral
      therapy, 1 hyponatriemic syndrome which required an intraperitoneal drainage and
      1 global kidney functional exclusion after 3 months. Etiopathogenesis and
      suggestions for prevention are discussed as well as the necessity of adequate
      training.

PMID- 9557503
TI  - [Mullerian duct cysts. Description of two cases with a minimally invasive
      therapeutic approach].
AB  - Among cystic lesions of the male pelvis, the mullerian duct cyst represents the
      most commonly recognized abnormality. These lesions are midline in location and
      should not be confused with the big or cystic utricle because of its different
      embryologic development. The cysts are usually small and asymptomatic. Two cases
      of big and symptomatic mullerian cysts treated by minimal invasive approach
      consisting of aspiration and endoscopic marsupalization are presented.

PMID- 9557504
TI  - [Liposarcoma of the spermatic cord].
AB  - A case of well differentiated liposarcoma of the spermatic cord in a 80 year old
      man is presented. The preoperative diagnosis of spermatic cord liposarcoma is not
      easy; however, a careful comparison between clinical and ultrasonographic
      findings can lead to diagnostic suspicion. The treatment of choice is the
      excision of the liposarcoma associated with orchiectomy and high ligation of the
      spermatic cord to reduce the risk of recurrence. Postoperative radiotherapy may
      be indicated for poor differentiated liposarcomas.

PMID- 9557505
TI  - [Renal multifocal carcinoma with adrenal gland metastasis in a patient previously
      treated with radical nephrectomy: what kind of therapy. Review of the
      literature].
AB  - A case of multiple adrenal metastases due to renal cells carcinoma, associated
      with a multifocal simultaneous renal cells carcinoma has been observed in a
      female patient previously submitted to radical contralateral nephrectomy for the
      same disease. In particular, stress is laid on computerized tomography scan
      diagnosis and surgical procedure.

PMID- 9557506
TI  - Augmentation ileocystoplasty in a case of eosinophilic cystitis.
AB  - Eosinophilic cystitis (EC) is a rare form of bladder inflammation characterized
      by massive eosinophilic infiltration of the bladder wall. The most frequent signs
      and symptoms are pollakiuria, urgency, macroscopic haematuria and hypogastric
      pain: the involvement of the ureters may cause hydronephrosis and renal failure.
      Eosinophilia and eosinophiluria are present in 35% and in 50% of the cases
      respectively. EC may evolve towards sclerosis up to the anatomoclinical picture
      of small retracted bladder, which requires to be differentiated from tubercular
      cystitis, interstitial cystitis and cancer. Imaging techniques are not definitely
      diagnostic. Diagnosis can be reached only by biopsy with the microscopic
      demonstration of eosinofilic infiltration of the whole bladder wall in the early
      and acute stages, while fibrosis with poor cellularity predominates in the
      chronic stages. Etiology is unknown and the hypothesis of an allergic origin is
      unproved even though remissions or recoveries induced by steroidal therapy have
      been reported. Surgical therapy of EC, as in our observation, is absolutely
      required to correct urgency and incontinence and to prevent renal failure when
      the urinary upper tract has been primarily or secondarily involved.

PMID- 9557508
TI  - What can be done about Indian medical research?

PMID- 9557507
TI  - [Recurrent urinary tract infections. Biological suppositions and clinical
      treatment with thymopentin].
AB  - BACKGROUND: Urinary tract infections (UTI) are a common usual pathological event.
      They relapse often due to the periurethral colonization of microorganisms from
      the intestinal bacterial flora. They also constitute an important and
      considerable social and clinical problem. The absence of inducing organic
      conditions or an infective focus at the base of the pathogenetic mechanism
      suggests the existence of alterations of the immune response of the subject.
      MATERIALS AND METHODS: In this work we wanted to verify if, in those subjects
      with relapsing UTI (more than four events every year) cure with "biological"
      response modifiers, particularly "thymopentin", meaningfully reduced the number
      of events. RESULTS: The results obtained confirm that for those cases in which
      the chemo-antibiotic therapy did not have the expected results, it is rational to
      support it with an immune-modulating drug (thymopentin). In fact the post-therapy
      reduction of UTI observed during two years of follow-up is statistically
      significant when compared to the average of UTI before therapy. CONCLUSIONS: The
      "cost-benefits" analysis should prove to be a saving in favour of the use of
      thymopentin, taking into consideration the reduction of chemo-antibiotics
      consumption and the lower number of working hours lost every year.

PMID- 9557509
TI  - Continuous ambulatory peritoneal dialysis in India.

PMID- 9557510
TI  - Prevalence of Helicobacter pylori infection in disorders of the upper
      gastrointestinal tract in south India.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is the most common human infection.
      Though most individuals are asymptomatic, H. pylori plays a key role in the
      aetiology of many upper gastrointestinal disorders. The prevalence of duodenal
      ulcer in south India is high but there are very few reports regarding the
      prevalence of H. pylori infection in various upper gastrointestinal disorders in
      south Indians. Therefore, we studied the prevalence of H. pylori infection in
      upper gastrointestinal disorders in south Indians. METHODS: Three hundred and
      thirty-five patients with various upper gastrointestinal disorders were included
      in the study. Seventy-five patients with no gastrointestinal disease based on
      symptoms and endoscopy were taken as controls. The H. pylori status was
      determined by the urease test, serology and histology and the prevalence compared
      between various upper gastrointestinal disorders, with controls and with one
      another. RESULTS: The prevalence of H. pylori was high in the patients and
      controls. Duodenal ulcer patients had a significantly higher prevalence compared
      to controls (p < 0.001) and those with other upper alimentary disorders. There
      was no significant difference between patients with other disorders and controls
      nor between each other (p > 0.05). CONCLUSION: The prevalence of H. pylori
      infection is high in south India. It is closely associated with duodenal ulcer.
      More population-based studies are required to evaluate the relationship of H.
      pylori with other disorders of the upper gastrointestinal tract.

PMID- 9557511
TI  - Iodine deficiency disorders in Car Nicobar (Andaman and Nicobar Islands).
AB  - BACKGROUND: The term 'Iodine deficiency disorders' (IDDs) reflects the spectrum
      of health effects due to iodine deficiency at all ages. So far, no survey for IDD
      has been carried out in the Andaman and Nicobar Islands (A&N). Therefore, we
      aimed to determine the status of IDDs at Car Nicobar Island and to assess the
      iodine content of salt available for consumption on the island. METHODS: The
      study population comprised tribal school children between 7 and 18 years of age
      in government schools of Car Nicobar, A&N. Children were selected from each
      school by the simple random sampling method using the random number table. The
      same sampling method was used for each school till completion of the desired
      sample size for that school. Casual urine samples (in screw-capped plastic
      bottles for iodine estimation) and blood samples (on No. 3 Whatman filter paper
      for TSH estimation) were collected from a randomly selected sub-sample of
      students. Salt samples for iodine estimation were collected from 'captains'
      (village headman) of each village and the headmasters of the schools and
      'canteens' in government retail outlets in the villages. RESULTS: Of the 969
      children surveyed, 160 (16.5%) had goitre. The prevalence was significantly more
      among females (23.6%) than males (9.7%). Analysis of 105 urine samples showed
      that the median urinary iodine excretion level was 7.0 micrograms/dl. The median
      TSH values in subjects was 5.7 mU/L. Fifty (82.5%) of the 54 salt samples had
      adequate iodine (> or = 15 parts per million). CONCLUSIONS: IDDs pose a mild-to
      moderate public health problem in Car Nicobar Island. The supply of iodized salt
      and its iodine content was found to be satisfactory at the time of the study.

PMID- 9557512
TI  - Attitudes of medical and nursing students towards blood donation.
AB  - BACKGROUND: Data on the attitudes of medical and nursing students towards blood
      donation are scanty. Since this group is a potential but under-utilized source of
      blood donors, studying their attitudes could provide insights into donor-related
      behaviour and, hence have implications for donor recruitment programmes. METHODS:
      The attitudes towards blood donation and frequency of donation of 307 medical and
      nursing students were studied using a scale to measure affect, behaviour and
      cognition. RESULTS: The attitudes were found to be positive in all three scales.
      While the behaviour scale significantly discriminated donors from non-donors, no
      significant differences were observed in the affect and cognition scales.
      CONCLUSION: In a medically-oriented population, donors and non-donors do not
      differ significantly in their sentiments towards blood donation. Other social
      variables may account for donor behaviour which need to be studied further.

PMID- 9557514
TI  - Is a 'lot' necessarily better than a 'little'? Impact of aggressive cardiac
      revascularization strategies.

PMID- 9557513
TI  - Aspirin: a neuroprotective agent at high doses?
AB  - Aspirin, acetylsalicylic acid, is routinely used in clinics as an analgesic,
      antipyretic and in the secondary prevention of stroke. These effects are caused
      by low doses of the drug (0.3-3.6 g/day) through the inhibition of cyclo
      oxygenase, the enzyme responsible for prostaglandin synthesis. Higher doses of
      aspirin (4-6 g/day) are used in the treatment of inflammatory conditions such as
      rheumatoid arthritis and recent laboratory findings suggest that it could play a
      role in neuroprotection against glutamate excitotoxicity. This article reviews
      the possible mechanisms of action of high-dose aspirin in neuroprotection.

PMID- 9557515
TI  - Autologous bone marrow transplantation in chronic myeloid leukaemia.

PMID- 9557516
TI  - Cost-effectiveness of cardiovascular screening and intervention programmes.

PMID- 9557517
TI  - Teaching research methodology to postgraduates: is dissertation the only method?

PMID- 9557518
TI  - MD/MS dissertations--the case in favour.

PMID- 9557519
TI  - Does India perform medical research in areas where it is most needed?
AB  - This paper attempts to map medical research in India and answer an important
      policy question by literature analysis. I match the disease pattern on the basis
      of mortality and morbidity statistics with journals used by Indian medical
      researchers to publish their work as shown by the Science Citation Index (SCI).
      The former reflects the needs while the latter reflects the areas in which
      research is being done. The limited statistics available from both the Government
      of India and the World Health Organization point to diarrhoeal diseases, diseases
      of children, respiratory diseases, circulatory system diseases, infectious
      diseases, malaria and tuberculosis as the major medical problems faced by India.
      The journals used often by Indian medical researchers to publish their work, as
      seen from the SCI (1981-85), show that in terms of number of publications, they
      are mainly active in general medicine, pharmacology, tropical medicine,
      neurosciences, radiology, oncology and pathology. In terms of the share of the
      world's literature in different subfields, India is second only to USA in
      andrology, third in tropical medicine after the USA and the UK, tenth in hygiene
      and public health, and eleventh in general and internal medicine, and radiology
      and nuclear medicine. Overall, India's share in the medical journal literature is
      not only much less than that of many other countries, both advanced and middle
      level, but also much less than that of India's share of the literature in
      physics, chemistry, mathematics and engineering. Data on the observed citation
      impact of Indian research in different subfields of medicine show that the work
      done in India in general is not integrated well into international research.
      India could be much more purposive in her research priorities and probably should
      invest much more in medical research.

PMID- 9557520
TI  - New government--new start for health?

PMID- 9557521
TI  - Monsoon delights.

PMID- 9557522
TI  - An intradermal vaccine protocol against hepatitis B in a haemodialysis
      population.

PMID- 9557523
TI  - Distribution of vascular lesions in ischaemic stroke.

PMID- 9557524
TI  - Quality of life in cancer: the emerging arbiter.

PMID- 9557525
TI  - Supplementary feeding component of the ICDS for expectant women.

PMID- 9557526
TI  - New criteria for liver transplantation in adults: the combined Groningen and
      Rotterdam protocol.
AB  - A combined protocol for liver transplantation has been written by the teams of
      Groningen and Rotterdam. This is to ensure that the criteria for selection and
      timing of liver transplantation, and the procedures for patient evaluation, are
      identical or at least very similar. Also, the waiting list procedures in the two
      centres, including the criteria used to decide which patient will be transplanted
      first, are very similar. Currently, most patients with liver cirrhosis or
      filminant liver failure should be considered as liver transplant candidates
      unless a contraindication is found. Most contraindications are relative and are
      the subject of a careful balance of pros and cons. The detection and care of
      liver patients starts with the general practitioner. Referral to liver
      transplantation centres is the final step. In the Netherlands, liver disease is
      relatively rare and therefore patients are best served when the expertise is
      concentrated in a few liver centres.

PMID- 9557527
TI  - The effect of renal transplantation on hyperhomocysteinaemia in dialysis
      patients, and the estimation of renal homocysteine extraction in patients with
      normal renal function.
AB  - BACKGROUND: The pathophysiology of hyperhomocysteinaemia in chronic renal failure
      (CRF) is unknown. Possible mechanisms are decreased renal homocysteine (Hcy)
      catabolism or inhibition of extrarenal Hcy metabolism by uraemic toxins. METHODS:
      We studied the short-term effect on plasma Hcy concentration of improvement of
      renal function after successful kidney transplantation (n = 8), and determined
      renal Hcy extraction by measurement of total Hcy in arterial and renal venous
      blood in 7 cardiac patients with normal renal function. RESULTS: Post
      transplantation, plasma Hcy decreased with improving renal function. In the
      cardiac patients, no significant renal Hcy extraction could be demonstrated, but
      tubular disposal of the filtered load could not be excluded. CONCLUSIONS: Because
      loss of such renal metabolism could lead to hyperhomocysteinaemia in CRF, it is
      necessary to determine the renal extraction of free Hcy in subjects with normal
      renal function to further investigate renal homocysteine metabolism.

PMID- 9557528
TI  - Pretreatment serum LDH as additional staging parameter in small-cell lung
      carcinoma.
AB  - BACKGROUND: In patients with limited disease staged small-cell lung cancer
      (SCLC), overall survival is still poor. Therefore, a retrospective study was
      carried out of 48 patients with limited disease staged SCLC to select a parameter
      which can identify prognostic subgroups at the time of diagnosis. MATERIALS AND
      METHODS: Follow-up varied from 3 to 96 months during which 38 patients died.
      Based on clinical outcome, patients were clustered into three groups: complete
      remission (CR) (n = 16); local recurrence (LOC) (n = 7); and distant recurrence
      (DIS) (n = 25). Age, gender and pretreatment biochemical parameters were
      correlated with clinical outcome and survival. RESULTS: No differences in
      survival were found in patients with LOC (14% 2-year survival) and DIS (16% 2
      year survival) (P = 0.67). Patients with complete remission demonstrated a
      significantly better survival (75% 2-year survival). LDH was found to be the only
      significant correlate of both tumour progression and survival. All patients with
      pretreatment LDH levels > 240 IU/l (n = 13) demonstrated tumour recurrence. The
      survival rate of patients with LDH levels < 240 IU/l (41% 2-year survival) was
      much better than that of patients with LDH levels > 240 IU/l (8% 2-year survival)
      (P = 0.0001). CONCLUSION: LDH may be used for the identification of prognostic
      subgroups in limited disease SCLC. Patients showing pretreatment LDH levels > 240
      IU/l have an extremely high risk of tumour recurrence, whereas survival is poor.
      In patients with LDH levels, < 240 IU/l survival is significantly better.

PMID- 9557529
TI  - Aortic graft infection by Lactobacillus casei: a case report.
AB  - A 65-year-old man with an abdominal aortic endoprosthesis presented with fever
      without other symptoms. Investigations revealed Lactobacillus casei bacteraemia.
      The Lactobacillus graft infection was at first successfully treated by antibiotic
      therapy. However, during follow-up a relapse occurred, and after surgical
      replacement of the graft the patient was cured. At surgery an aortoenteric
      fistula was found as source of the infection.

PMID- 9557530
TI  - Primary thyroid lymphoma.
AB  - A 71-year-old woman presented with a rapidly growing goitre which was diagnosed
      as chronic autoimmune thyroiditis. Despite treatment with levothyroxine, she
      developed progressive airway obstruction. Biopsy revealed a primary thyroid
      lymphoma which was successfully treated with radiotherapy.

PMID- 9557532
TI  - Depression and myocardial infarction: implications for medical prognosis and
      options for treatment.
AB  - Mental depression and myocardial infarction (MI) are closely related. The current
      paper reviews pathophysiological mechanisms that could link depression to MI and
      discusses the pros and cons of different pharmacological and non-pharmacological
      treatment modalities that could be considered. The selective serotonin reuptake
      inhibitors lack arrhythmogenic effects, and have a beneficial effect in addition
      to depression on psychological factors, such as anxiety and mood disturbances,
      which are not uncommon in post-MI patients. Studies to further determine the
      impact of depression on the outcome of MI, and the place of different treatment
      modalities are in progress.

PMID- 9557531
TI  - Hypereosinophilic syndrome presenting with diarrhoea and anaemia in a patient
      with systemic lupus erythematosus.
AB  - We describe a patient with quiet systemic lupus erythematosus who developed a
      hypereosinophilic syndrome. The patient presented with gastrointestinal
      eosinophilia which caused diarrhoea, malabsorption and anaemia due to
      deficiencies of vitamins. The hypereosiniphilic syndrome completely resolved
      after treatment with prednisone.

PMID- 9557533
TI  - Modulatory role of protein tyrosine kinase activation in the receptor-induced
      contractions of the bovine cerebral artery.
AB  - Changes in contractile force were measured during isometric contraction of the
      bovine middle cerebral artery caused by stimulation of various receptors and by
      application of high K+, caffeine, and protein kinase C (PKC)-activators. The
      protein tyrosine kinase (PTK)-inhibitors, such as genistein and tyrphostin, were
      applied before testing the effect on the contractions or during the maximal
      plateau of the contraction. The contractions induced by serotonin, prostaglandin
      F2 alpha, endothelin-1, and thromboxane A2 were significantly and dose
      dependently depressed by the PTK-inhibitors (IC50 2-15 microM). In contrast,
      contractions were significantly augmented by 1 microM pervanadate, an inhibitor
      of phosphoprotein tyrosine phosphatase. Lineweaver-Burk plotting of the dose
      response curves with an increase in inhibitor concentration indicated that the
      receptor affinity for each agonist remained unchanged in spite of marked
      depression of the responses. Although the effect was not significant,
      contractions induced by both high K+ and caffeine were also depressed slightly by
      PTK-inhibitors in the same range of concentrations used for receptor-induced
      contractions. Contractions induced by PKC-activators, such as 1-oleoyl-2-acetyl
      sn-glycerol and phorbol-12,13-diacetate, were significantly depressed by PTK
      inhibitors at concentrations similar to those used for receptor-induced
      contractions. The results suggest that receptor stimulations which produce
      sequential activation of phospholipase C and PKC can activate PTK and trigger the
      so-called "PTK-cascade" causing a sustained or long-lasting contraction similar
      to the cerebral vasospasm observed clinically.

PMID- 9557534
TI  - Roentgenological study of the sagittal diameter of the cervical spinal canal in
      normal adult Japanese.
AB  - The sagittal diameter of the cervical spinal canal on roentgenograms in normal
      adult Japanese aged 15 years or over, 505 males and 492 females, was investigated
      to define the normal distribution and lower limit. Lateral roentgenograms of
      cervical spinal canals were taken at a constant focus-film distance of 1.5 m. The
      mean +/- SD magnification coefficient was 1.17 +/- 0.02. The mean +/- SD sagittal
      diameters of the cervical spinal canals at each vertebral level were: C-1, 21.0
      +/- 2.2 mm; C-2, 18.0 +/- 1.7 mm; C-3, 15.8 +/- 1.5 mm; C-4, 15.2 +/- 1.5 mm; C
      5, 15.3 +/- 1.5 mm; C-6, 15.7 +/- 1.5 mm; and C-7, 15.9 +/- 1.4 mm. The lowest
      mean -2 SD values were: C-1, 16.6 mm; C-2, 14.6 mm; C-3: 12.8 mm; C-4, 12.2 mm; C
      5, 12.3 mm; C-6, 12.7 mm; and C-7, 13.1 mm. The smallest diameter was at the C-4
      level, but there was no significant difference between values at the C-4 and C-5
      levels. Males had significantly larger diameters than females (mean difference
      0.8 mm) (p < 0.01). Younger subjects had greater diameters than older subjects.
      The incidence of spondylotic changes was 40.1% in subjects aged 50-59 years,
      57.7% in those aged 60-69 years, and 76.6% in those aged 70-79 years. Males had a
      higher incidence than females. Ossification of the posterior longitudinal
      ligament was observed in 2.1% of all subjects. This study suggests that patients
      with a sagittal diameter in the cervical spinal canal of less than 12 mm have a
      high risk of cervical myelopathy.

PMID- 9557535
TI  - Third ventricular neuroepithelial cyst originating from the massa intermedia-
      case report.
AB  - A 47-year-old female presented with a 3-year history of progressive emotional
      disturbance. Computed tomography and magnetic resonance imaging revealed a cyst
      in the third ventricle causing hydrocephalus. Endoscopic surgery found the cyst
      originated at the massa intermedia. Histological examination confirmed the
      diagnosis of neuroepithelial cyst. Neuroepithelial cyst originating from the
      massa intermedia may be due to persistence of neuroepithelial crest at this
      location.

PMID- 9557536
TI  - Autopsy findings in a long-term survivor with glioblastoma multiforme--case
      report.
AB  - Autopsy detected no tumor tissues in a patient who died 6.5 years after the
      diagnosis of glioblastoma multiforme. A 54-year-old male developed left
      hemiparesis one month prior to admission. Computed tomography demonstrated a
      cystic lesion in the right frontal region with irregular ring-like enhancement.
      The tumor was extensively removed together with the surrounding tissue followed
      by irradiation (whole brain 32.4 Gy, local 28.8 Gy), and intravenous
      administration of interferon-beta. Histological examination confirmed the
      diagnosis of glioblastoma multiforme. He died of accidental head trauma 6.5 years
      after surgery. Autopsy of the brain detected no evidence of glioblastoma
      multiforme. The only findings were cerebral edema and hematoma caused by head
      trauma, as well as histological changes due to radiation damage. This case
      apparently confirms the histological disappearance of tumor tissue in a long-term
      survivor with glioblastoma multiforme.

PMID- 9557537
TI  - Facial spasm and paroxysmal tinnitus associated with an arachnoid cyst of the
      cerebellopontine angle--case report.
AB  - A 59-year-old female presented with a 3-year history of hemifacial spasm and
      paroxysmal tinnitus associated with an arachnoid cyst of the cerebellopontine
      angle, which was identified preoperatively by magnetic resonance imaging.
      Surgical decompression of the cyst and arterial decompression of the facial and
      acoustic nerves at their root exit zones resulted in complete resolution of the
      symptoms.

PMID- 9557538
TI  - Magnetic resonance imaging of non-specific inflammatory granulation involving the
      skull base--two case reports.
AB  - A 55-year-old male presented with a 20-day history of nuchal pain and hypoglossal
      nerve paresis on the right. T2-weighted magnetic resonance (MR) imaging showed an
      isointense lesion with a small hypointense part in the hypoglossal canal and
      caudal clivus. A 66-year-old female presented with a long-standing history of
      left orbital pain. T2-weighted MR imaging showed a hypointense lesion occupying
      the orbital apex which on recurrence became isointense. The histological
      diagnosis of both lesions was non-specific inflammatory granulation. The T2
      weighted MR imaging appearance of this entity is variable, and can change within
      the clinical course of the same lesion.

PMID- 9557539
TI  - Usefulness of neuroendoscopy in treating supracollicular arachnoid cysts--case
      report.
AB  - A 12-year-old girl presented with a supracollicular arachnoid cyst manifesting as
      a compressive headache. Neurological examination on admission revealed no deficit
      except bilateral papilledema. Stereotactic cyst puncture failed to perforate the
      cyst wall. The wall was then punctured using microforceps under neuroendoscopic
      guidance, followed by cystoperitoneal shunting. Her headache disappeared
      immediately after surgery. Neuroendoscopy is useful in treating a deep-seated
      arachnoid cyst.

PMID- 9557540
TI  - Surgical correction of trigonocephaly: theoretical basis and operative
      procedures.
AB  - Trigonocephaly involves premature fusion of both the metopic suture and the
      sutures in the skull base. Surgical treatment by opening of the prematurely fused
      metopic suture and expansion of the anterior cranial base by creating
      "neosutures" was used to treat three children with trigonocephaly. The
      combination of lateral canthal advancement and radical forehead remodeling
      achieved excellent results. These procedures can also prevent the development of
      midface hypoplasia such as hypotelorism. The two younger patients, aged 0 and 6
      months, achieved rapid bone growth in the defects and normalization of
      intercanthal and interpupillary distances. The older patient, aged 8 years,
      retained some skull defects at follow-up. The optimal age for surgery is 3-6
      months, which allows good cosmetic results and minimizes visual repercussions
      with relatively low perioperative risks.

PMID- 9557541
TI  - [Psychopathological alteration of the auditory structure in schizophrenia; "the
      experience of no-sounds"].
AB  - According to recent cognitive theories, the greater part of the perceptional
      meaning and representative meaning are both pre-determined, or pre-organized as a
      set of meaning, which has a biophysiological and socio-cultural origin. Humans
      however, drive some kind of sensational Gestalt from each sense organ, and this
      is incapable of being transformed into language (representative pre-meaning),
      this enabling us to experience the possibility of truly private meaning in our
      own right. The author has emphasized this two moments of the meaning, that is,
      private moments of meaning vs. institutional moments. The author has offered the
      phenomenological hypothesis of auditory experience and elaborated the relation
      between these two moments in it. Then, the author has testified its validity in
      the process of describing and analysing the pathological alteration of auditory
      sensation in schizophrenia. Auditory space is thought to be differentiated into a
      three-dimensional structure. That is, a dimension of background, a dimension of
      signs, and a dimension of symbols, and we accept environmental-sounds, event
      sounds, symbolic sounds in each level. Close investigations about 5
      schizophrenics revealed that these patients undergo a strange silent experience
      before the onset of delusional ideas, descriptively and phenomenologically, this
      phenomenon appeared to be initiated by the deprivation of the dimension of
      background sounds (referred to as "the experience of no-sounds"). This
      experiences often occurred especially when they are eager to listen to the
      surrounding sounds (for example, noises in the neighborhood, classroom chatter),
      in order to solve their own interpersonal difficulties. Furthermore, the author
      described the ambivalent nature of patients' thinking in this pathological
      auditory situation, in which one idea of the polarity of dichotomy was forced to
      switch to the another one, influenced by an attribute of surrounding sounds. With
      regard to this aspect, the patients experienced both the physiological changes in
      the auditory structure as well as the psychological turmoil. The author has
      emphasized the need to appreciate this ambiguous nature of the psychological
      context mixed with the physiological context, which is supposed to be very
      important from psychotherapeutical viewpoint.

PMID- 9557543
TI  - [A survey of drug utilization in psychiatric hospitals in Japan: the basic
      analysis of the current status of prescription patterns].
AB  - Although concern about the prescription pattern of psychotropics is growing,
      there have been very few surveys in Japan. In this survey conducted in 1993,
      prescription data, patient characteristics, etc. were collected for 2,395
      inpatients from 18 psychiatric hospitals. Their mean age was 48.4 (S.D. = 13.6).
      Of these patients, 1,818 (75.9%) were diagnosed with schizophrenia, 115 (4.8%)
      with mood disorder, and 102 (4.3%) with mental retardation. The results were as
      follows. 1) They were prescribed an average of 10.1 different drugs: of these,
      5.6 were various psychotropics (2.6 neuroleptics, 1.2 antiparkinsonian drugs, 1.0
      hypnotics). 2) The mean daily dose of antipsychotics was 1,082 mg of
      chlorpromazine equivalent. 3) The most commonly prescribed neuroleptic was
      haloperidol (53.2% of the total patients) followed by levomepromazine (48.7%),
      chlorpromazine (24.8%), bromperidol (18.7%), and zotepine (18.3%).

PMID- 9557542
TI  - [A study on late catatonia--the psychopathological study of its symptoms,
      courses, subtypes, and treatments].
AB  - It was discussed at the beginning of this century whether to categorize "late
      catatonia" in "manic-depressive disorder", in "schizophrenia", or to consider
      itself as another clinical entity. Sommer was the first to make a clinical report
      on "late catatonia"; however Kraepelin had reported on cases with very similar
      symptoms prior to Sommer, and called them "involutional melancholia" or
      "presenile psychosis". Followed by a couple of decades, Jacobi's clinical report
      gave "late catatonia" the impressions as having a very poor prognosis. It was
      then stated by M. Bleuler that approximately 30% of "late schizophrenia" was well
      fitted into "late catatonia". According to Huber who carried out a survey
      utilizing the same criterion for "late schizophrenia" some 30 years later, no
      such concordance was found. Hence, it may be said that some kind of change in
      symptoms has occurred. Symptom-transitions of 16 "late catatonia" subjects were
      analysed in detail. "Late catatonia" is a symptomatic concept with characteristic
      progressive symptoms: Stage 1 (prodrome and primary depression), Stage 2
      (anxiety, irritation), Stage 3 (hallucination, delusion), Stage 4 (catatonia),
      and the residual stage. "The complete type" which progresses to Stage 4 stepwise,
      may end up developing "malignant catatonia". In this case, it may be life
      threatening unless suitable treatment is carried out. This disease may be divided
      into 2 types of clinical courses; a multi-phasic course with intermittent
      remission, and a mono-phasic course which is chronic. Transition to the residual
      stage may occur at any point. In practice, there are 3 other subtypes; these
      three are called "the abortive types" (anxious/irritated type,
      depressive/delusional type, residual type). These cases are most typically
      considered as depression with severe anxiety and irritation, and in case
      flattening of affect becomes the major symptoms, it is often misdiagnosed as
      "organic dementia". Considering treatment, the majority was nonrespondent to
      neuroleptics, especially those at stage 4; however, ECT (electroconvulsive
      therapy) was observed to be effective in some cases.

PMID- 9557544
TI  - [Sexuality in bacteria].

PMID- 9557545
TI  - [Molecular mechanisms for the regulation of meiosis in fission yeast].

PMID- 9557546
TI  - [Sexual reproduction and gametogenesis in algae].

PMID- 9557548
TI  - [Conjugation in protozoa].

PMID- 9557547
TI  - [Sexual reproduction in cellular slime molds: a prototypic mating system].

PMID- 9557550
TI  - [Mechanism underlying germline formation in Drosophila melanogaster].

PMID- 9557549
TI  - [Germ-line stem cells and sex determination in hydra].

PMID- 9557551
TI  - [Sex and reproduction in the nematode C. elegans].

PMID- 9557552
TI  - [Origin and differentiation of primordial germ cells in teleost].

PMID- 9557553
TI  - [Formation of primordial germ cells (PGCs) in amphibia].

PMID- 9557554
TI  - [Formation and migration of avian primordial germ cells].

PMID- 9557555
TI  - [Developmental potential of embryonic and somatic cells in mammals].

PMID- 9557556
TI  - [The origin and development of mammalian germ cell line].

PMID- 9557557
TI  - [Gene expression in mouse primordial germ cell].

PMID- 9557558
TI  - [Proliferation and differentiation of mouse fetal germ cells].

PMID- 9557559
TI  - [Functional analyses of mammalian spermatogenic genes].

PMID- 9557560
TI  - [Mechanism of gonadal differentiation and spermatogenesis in teleost].

PMID- 9557561
TI  - [Mechanism of spermatogenesis in amphibians].

PMID- 9557562
TI  - [Mechanisms of sex-determination in Drosophila].

PMID- 9557563
TI  - [Sex determination and differentiation in amphibians].

PMID- 9557564
TI  - [Sexual differentiation of gonads and gametogenesis in the avian species].

PMID- 9557565
TI  - [Sex-determining genes and gonadal sex differentiation in mammals].

PMID- 9557566
TI  - [Differentiation of mammalian gonads].

PMID- 9557568
TI  - [Mutations affecting germ cell development and teratocarcinogenesis in mice].

PMID- 9557567
TI  - [Functions of TGF-beta superfamily members in reproduction].

PMID- 9557569
TI  - [Spermatogenesis in mammalian testis].

PMID- 9557570
TI  - [Zygote-constructing ability of spermatogenic cells in mammals].

PMID- 9557571
TI  - [Cell cycle control through meiotic and early cleavage cycles].

PMID- 9557572
TI  - [Genomic imprinting and mammalian development].

PMID- 9557573
TI  - [Genomic imprinting in germ cells].

PMID- 9557574
TI  - [Imprinted X chromosome inactivation].

PMID- 9557575
TI  - [Genomic imprinting during oogenesis and embryonic development].

PMID- 9557576
TI  - [Studies of genomic imprinting using mouse cells containing a human chromosome].

PMID- 9557577
TI  - [Genetic control of flowering: transition from vegetative to reproductive
      growth].

PMID- 9557578
TI  - [Molecular genetic analysis of flower formation].

PMID- 9557579
TI  - [Germ cell formation and gametophyte differentiation in higher plants].

PMID- 9557580
TI  - [Sex determination and sex expression in higher plants].

PMID- 9557581
TI  - [Plasticity in sex expression of angiosperm].

PMID- 9557582
TI  - Expanded Programme on Immunization (EPI). Progress towards elimination of measles
      in the Americas.

PMID- 9557583
TI  - Environmental health services in Europe. 1. An overview of practice in the 1990s.

PMID- 9557584
TI  - An empirical study of preferred settings for lumbar support on adjustable office
      chairs.
AB  - The preferred settings for lumbar support height and depth of 43 male and 80
      female office workers were investigated. All subjects were equipped with
      identical modern office chairs with foam-padded backrests adjustable in both
      height and depth. Measurements of lumbar support settings were recorded in the
      workplace, outside of working hours, on four different occasions, over a 5 week
      period. Preferred lumbar support height and depth settings extended to both
      extremes of the adjustment range. The mean preferred height setting was 190 mm
      above the compressed seat surface. The mean depth setting (horizontal distance
      from front of seat to lumbar support point) was 387 mm. A regression model
      examining the effects of standing height, Body Mass Index (BMI) and gender on
      mean preferred lumbar support height showed a significant relationship between
      preferred height and BMI. Higher lumbar supports were chosen by subjects with
      greater BMIs. Gender and standing height were not associated with preferred
      lumbar support height settings. Preferred lumbar support depth was not
      significantly associated with standing height, gender or BMI. Older subjects were
      more likely to readjust their lumbar support from a disrupted position than
      younger subjects, indicating that older users are more sensitive to the position
      of their lumbar support. Subjects who reported recent back pain or discomfort
      that they believed to be associated with their chair or office work were found to
      set their lumbar support significantly closer to the front of the seat, probably
      to ensure greater support for their back. Based on the evidence that a high
      proportion of users do make adjustments to the height and depth of their lumbar
      support, and the finding that different groups of users, with different physical
      characteristics, adjust the position of their lumbar support in distinct and
      predictable ways, the researchers conclude that office chairs with traditional
      padded fixed-height lumbar supports are unlikely to provide a comfortable or
      appropriate seat for the wide range of potential users.

PMID- 9557585
TI  - What is 'heavy'?
AB  - One of the work practices frequently taught to employees is to estimate the
      heaviness of load before it is actually handled. If it is 'heavy', then one
      should ask for help. However, limited information can be found in the ergonomics
      literature about what a person perceives as a 'heavy load'. This study was
      conducted on 20 male and 20 female workers in the package delivery industry to
      estimate the amounts of load that correspond to various levels of load heaviness
      (e.g. 'somewhat heavy'). Experienced employees were used for this purpose. The
      distribution of loads within each heaviness level was developed using fuzzy sets
      theory. The maximum load (i.e. 23 kg) defined by the US National Institute for
      Occupational Safety and Health represents a 'somewhat heavy' load based on the
      analysis of load distribution (corresponding to a 1.0 certainty factor). Also,
      the 40 kg considered in the 1981 NIOSH guidelines may be classified as a 'very
      heavy' load. A comparative analysis of the results of this study with norms
      established in prior research indicates that one should be more careful in the
      interpretation of statistical norms for human perception of load handling. A
      'moderate' level of load heaviness (i.e. 14 kg) can be handled by 85% of the
      worker population.

PMID- 9557586
TI  - The impact of flicker from fluorescent lighting on well-being, performance and
      physiological arousal.
AB  - In working environments all over the world, fluorescent tubes are by far the
      dominating light source. Still, there have been very few studies on the impact of
      the non-visible flicker from fluorescent tubes. The purpose of the study was to
      compare the impact on subjective well-being, performance and physiological
      arousal of fluorescent light powered by conventional and high-frequency ballasts.
      Thirty-seven healthy males and females were subjected to either condition in a
      laboratory office on two separate occasions with 1 week in between. Although the
      methodology was quite extensive, only a few general effects were observed.
      However, when the light was powered by the conventional ballasts, individuals
      with high critical flicker fusion frequency (CFF) responded with a pronounced
      attenuation of EEG alpha waves, and an increase in speed and decrease in accuracy
      of performance. These results may be understood in terms of heightened arousal in
      the central nervous system in response to the pronounced light modulation caused
      by the conventional ballasts. In order to alleviate this potential stress source,
      it is recommended that fluorescent lighting be powered by electronic high
      frequency ballasts of good quality.

PMID- 9557588
TI  - Validation of a frequency-weighted filter for continuous biomechanical stress in
      repetitive wrist flexion tasks against a load.
AB  - This experiment validates a frequency-weighted filter for continuous measurements
      of force, posture and repetition using a stimulated industrial task. A peg
      transfer task was used requiring subjects to repetitively insert pegs into holes
      with controlled resistance. Ten subjects performed the task for six conditions.
      All wrist flexion angular data were recorded continually using an
      electrogoniometer and processed through the filter. Subjective discomfort was
      reported after performing the task for 1 h using a 10 cm visual analogue scale.
      Results from linear regression analysis showed that the instrument reliably
      estimated subjective discomfort (r2 = 0.873). Applications and limitations of
      this instrument are explored.

PMID- 9557587
TI  - Agreement between a frequency-weighted filter for continuous biomechanical
      measurements of repetitive wrist flexion against a load and published
      psychophysical data.
AB  - A previous pilot study demonstrated that a force and frequency-weighted filter
      network could be developed for processing continuous biomechanical measures of
      repetitive wrist motions and exertions. The current study achieves the objective
      by modelling subjective discomfort for repetitive wrist flexion using controlled
      posture, pace and force. A three-level fractional factorial experiment was
      conducted involving repetitive wrist flexion (2 s/motion, 6 s/motion, 10
      s/motion) from a neutral posture to a given angle (10 degrees, 28 degrees, 45
      degrees) against a controlled resistance (5 N, 25 N, 50 N) using a Box Behnken
      design. Ten subjects participated. Discomfort was reported on a 10 cm visual
      analogue scale. Results of response surface regression analysis revealed that
      main effects of force, wrist flexion angle, and repetition were all significant
      (p < 0.05) and that no second-order effects were observed. Linear regression
      analysis on these factors established a discomfort model on which the filter
      characteristics were based. The pure error test model revealed no significant
      lack of fit (p > 0.05). The continuous model was compared and agreed with
      discrete psychophysical data from other published studies. The model was used for
      generating parameters for a force and frequency-weighted digital filter that
      weighs continuous wrist postural signals with corresponding force in proportion
      to the equal discomfort function as a function of frequency of repetition. These
      filters will enable integration of large quantities of biomechanical data in
      field studies.

PMID- 9557589
TI  - Measures of operator performance in complex, dynamic microworlds: advancing the
      state of the art.
AB  - Microworld research provides a useful complement to field studies and highly
      controlled laboratory studies, aiming to strike a balance between
      representativeness and experimental control. Yet microworld research has
      associated methodological difficulties, particularly the problem of performance
      measurement. Researchers generally adopt a variety of measures to provide
      converging evidence concerning questions of interest. To confront problems with
      existing measures, this paper examines a series of objective measures used to
      characterize the performance of human operators in process control. These
      measures include novel, quantitative extensions to existing graphical analyses
      and new graphical representations. The measures are applied in the context of a 6
      month longitudinal study using an interactive, thermal-hydraulic process control
      microworld (DURESS II). The following measures are discussed: steady-state time,
      action transition graph complexity, the path length in state space diagrams, the
      area under distance-to-goals graphs, divergence from the temperature goal line in
      mass inventory versus energy inventory graphs, and the proportion of control
      actions near the beginning of the trials represented by timelines. Two case
      studies emphasize the performance and strategy differences of individual
      operators across the battery of measures.

PMID- 9557590
TI  - Exercise performance during inspiratory resistance breathing under exhaustive
      constant load work.
AB  - The purpose of this study was to determine the effects of different inspiratory
      resistances on exercise performance and to describe physiological and subjective
      responses during constant load work of an intensity that elicits the maximum
      sensitivity to respiratory factors of respirator wear. Nine subjects (mean age
      25.8 +/- 4.8 years) performed exhaustive treadmill exercise during constant load
      work of 80% of maximal aerobic capacity while inspiring against one of five
      randomly assigned inspiratory resistance conditions. For inspiratory resistances
      of 0.20 kPa (R1), 0.29 kPa (R2), 0.39 kPa (R3), and 0.49 kPa (R4), measured at a
      steady air flow rate of 85 L min-1, average performance times were 84, 75, 54,
      and 30% of the control condition. Performance time reductions were significant
      for R3 and R4 trials. Results also indicated a significantly reduced mean
      respiration rate, minute ventilation, and oxygen ventilatory equivalent (VE/VO2)
      for the R4 condition at exercise breakpoint compared to control. For resistances
      R1-R4, mean VE/VO2 were significantly reduced from control by approximately 12,
      17, 19, and 31%. At breakpoint, mean ratings of perceived exertion were similar
      for control, R1, R2, and R3 conditions but were significantly lower for R4 versus
      control. Breathing comfort did not differ significantly between resistances below
      the R3 level, but discomfort was significantly greater for conditions R3 and R4.
      These findings suggest that the impact of the respiratory limitations of
      respirators can be diminished by employing respirators with inspiratory
      resistances below the R3 level.

PMID- 9557591
TI  - Mental performance in extreme environments: results from a performance monitoring
      study during a 438-day spaceflight.
AB  - During their stay in a space habitat, astronauts are exposed to many different
      stressors that may entail detrimental effects on mood and performance. In order
      to monitor the effects of the space environment on different human information
      processing functions during an extraordinary long-term space mission, the
      cognitive. visuo-motor and time-sharing performance of one Russian cosmonaut was
      repeatedly assessed (29 times) during his 438-day stay in space. The performance
      tasks used were chosen from the AGARD-STRES battery and included grammatical
      reasoning, Sternberg memory-search, unstable tracking, and a dual-tasks
      consisting of unstable tracking with concurrent memory-search. In addition to
      performance assessment, several subjective ratings concerning mood and workload
      were collected. Comparisons of pre-flight, in-flight, post-flight and two follow
      up assessments 6 months after the mission revealed, (1) no impairments of basic
      cognitive functions during the flight, (2) clear impairments of mood, feelings of
      raised workload, and disturbances of tracking performance and time-sharing during
      the first 3 weeks in space and the first 2 weeks after return to Earth, (3) an
      impressive stability of mood and performance during the second to fourteenth
      month in space, where mood and performance had returned to pre-flight baseline
      level, and (4) no long-lasting performance deficits at follow-up assessments.
      From these results it is concluded that the first 3 weeks of long-term
      spaceflights and the first 2 weeks back on Earth represent critical periods where
      adverse effects on attentional processes are to be expected, induced by the
      demands to adjust to the extreme environmental changes. The stability of mood and
      performance observed after successful adaptation to the space environment
      indicates that mental efficiency and emotional state can be maintained on a level
      as high as on Earth even during extraordinary long-term space missions.

PMID- 9557593
TI  - The cells observed inside capsules of larvae in the course of experimental
      trichinellosis in mice.
AB  - In the course of trichinellosis in mice the numerous cells inside larval capsules
      were observed. Beginning on 14 day post infection (dpi) they were seen in about
      7% of infected muscles fibers but at 21 dpi the percentage of capsules with the
      cells amounted to 77. In the next stage of infection the number of capsules
      containing cells continued to increase and reach almost 100% at 60 dpi. The
      identification of the cells was carried out by the indirect immunoenzymatic
      method using anti-CD4+, anti-CD8+ and anti-macrophage (Mac-1 antigen) monoclonal
      antibodies. In course of observation the level of CD4+ cells decreased from 11.3
      to 0.7, of CD8+ from 17.7 to 3.0 and of macrophages from 71.0 to 23.1%. The most
      numerous CD4+ cells were seen at 14 dpi while the CD8+ and macrophages at 21 dpi.
      Beginning on 28 dpi negatively reacting cells inside larval capsules were also
      observed. The number of these cells increased from 23.8 to 73.2% at 60 dpi and
      their identification requires further investigations. The role and the function
      of all these cells are discussed.

PMID- 9557592
TI  - Macrophages during infection with Trichinella spiralis in mice.
AB  - Behaviour of macrophages in experimental mice trichinellosis was investigated
      using the immunoenzymatic technique with monoclonal antibodies CD11b/CD18 within
      the framework of avidin-biotin-DAB. The maximum and earliest mobilization of
      macrophages 7 day post infection (dpi) was observed in the lamina propria of the
      intestinal mucosa. The highest level of macrophages in the muscles tissue was
      noted on day 21 of infection, however as early as in 28 dpi, their maximum level
      was observed inside the larval capsules. They line, especially between 35-42 dpi
      internal capsule surface.

PMID- 9557595
TI  - Plasmapheresis in the treatment of trichinellosis.
AB  - Four patients with severe form of trichinellosis were treated with
      plasmapheresis. We noticed clinical improvement and favourable alterations in
      laboratory profiles (morphology and immune response parameters in the blood). The
      effect of plasmapheresis therapy in patients with trichinellosis was considered
      beneficial. No major complications of plasmapheresis were observed.

PMID- 9557594
TI  - Detection of Trichinella SP. invasion and clinical appraisal of patients in the
      late stage of trichinellosis in a new epidemic focus in Wielkopolska.
AB  - A clinical and an epidemiological analysis was presented of a trichinellosis
      focus from Wielkopolska region. The studies included 20 persons and
      trichinellosis was diagnosed in 15 cases. The focus was characterized by
      asynchronous invasion with Trichinella sp. in individual affected persons in the
      course of a prolonged period (around 2.5 months) and by reporting of the patients
      to the Clinic during approximately 30 to 90 days after the disease signs/symptoms
      developed. Retrospective analysis and a set of specialized tests permitted to
      clarify causes of persisting complaints, presented by the patients, as well as to
      establish the diagnosis at late stages of trichinellosis.

PMID- 9557596
TI  - Trichinellosis in Poland during recent 5 years (1992-1996).

PMID- 9557597
TI  - Epidemiological and epizootiological problems of trichinellosis in Poland.

PMID- 9557598
TI  - The red fox (Vulpes Vulpes) as reservoir of Trichinella sp. in Poland.

PMID- 9557599
TI  - Clinical aspects of late sequelae of trichinellosis.
AB  - Clinical analysis and the set of laboratory studies, performed in 25 patients
      one, two, three or six years after surviving acute period of trichinellosis,
      documented complaints in 22 patients (88.0%) in the form of muscle complaints
      (68.2%), cardiovascular complaints (45.4%), generalized weakness (40.9%) and
      fatigability (31.8%). No significant alterations were demonstrated in
      electrocardiographic records. In 71.4% examined patients lactic dehydrogenase
      activity was augmented. Presence of IgG antibodies against the E/S antigen of
      Trichinella sp. was disclosed in 24 (96%) patients, including 22 patients
      (88.0%), in whom high titres of the antibodies were found. Morphological studies
      on muscle tissue (performed in 5 patients) disclosed alterations typical of
      trichinellosis in 4 patients and presence of Trichinella larvae, calcified to a
      significant extent, in 2 patients. The long term persistence of IgG class
      antibodies against Trichinella antigen in patients who survived acute period of
      trichinellosis a few years earlier points to a chronic antigenic stimulation,
      probably reflecting progressive destruction of Trichinella larvae in muscle
      tissue. This may also be expressed in complaints reported by the patients. The
      problem requires further observations and clinical studies.

PMID- 9557600
TI  - All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the
      chronic phase.
AB  - Since in vitro observations indicated that all-trans retinoic acid (ATRA),
      especially in combination with IFNalpha, can exert significant suppressive
      effects on Ph+ cells, we investigated the effects and the pharmacokinetic profile
      of ATRA in a selected cohort of patients with Ph+ chronic myeloid leukemia (CML)
      in chronic phase. Eighteen patients were treated with ATRA at a dose of 80
      mg/m2/day (p.o.), divided into two equal doses after meals, for 7 consecutive
      days every other week for a maximum of 12 courses (1 course = 1 week on and 1
      week off). Pharmacokinetic profiles of ATRA were evaluated during intermittent
      therapy on days 1 and 7 of course 1; on day 1 of course 2; on day 1 of course 6.
      Out of the 18 patients treated with ATRA, 11 (61%) went off study before the
      sixth course of treatment because of progressive hyperleukocytosis (seven cases),
      or thrombocytosis (one case), or refusal (three cases). Seven (39%) patients
      completed the first six courses (12 weeks) of treatment with ATRA and two of them
      (11%) maintained a white blood cell (WBC) <10 x 10[9]/l which was induced by the
      pretreatment with hydroxyurea. One patient completed the 12th course of ATRA
      maintaining WBC <10 x 10(9)/l, platelets <500 x 10(9)/l and spleen not palpable.
      The treatment with ATRA was well tolerated and only one patient discontinued the
      therapy because of non-hematological side-effects. The area under the
      concentration-time curve (AUC) decreased significantly (P< 0.001) during the
      first week of therapy. By adopting an intermittent dosing regimen, 1 week on/ 1
      week off (1 course), at the start of courses 2 and 6, we obtained the ATRA AUCs
      equivalent to the ones achieved on day 1 of course 1. In conclusion, our results
      showed that ATRA alone appeared to be unable to control the WBC expansion in the
      CML patients in chronic phase. Moreover, it did not induce any remarkable
      cytoreductive effects on the platelet count and on the hemoglobin level. The
      major interest of ATRA would be in combination with other therapies. If ATRA was
      given in combination with IFNalpha or other agents, dose reduction of these would
      not be planned. On the basis of the pharmacokinetic profile, ATRA should be
      administered intermittently rather than continuously.

PMID- 9557601
TI  - Association of HLA phenotype and response to interferon-alpha in patients with
      chronic myelogenous leukemia.
AB  - Twenty to 25% of patients with chronic myelogenous leukemia (CML) treated with
      interferon-alpha (IFN-A) achieve a complete cytogenetic response (CCR). However,
      cells bearing rearrangement of BCR/ABL can still be detected many years after
      achieving a CCR despite the absence of clinical evidence of active disease. It
      has been suggested that the disease is kept in a dormant state by immune
      mechanisms. How this is achieved is not known, but it has been speculated that
      p210BCR/ABL might be presented by malignant cells through HLA molecules, thus
      making them the target for specific immune cell killing. Because specific
      peptides will be expressed in association with certain HLA molecules, different
      HLA phenotypes could be associated with different response rates to IFN-A. The
      response to IFN-A-based therapies in 239 patients with chronic phase CML was
      analyzed according to their HLA phenotype. One hundred and ninety-four (81%)
      achieved complete hematologic response, 142 (59%) had a cytogenetic response
      which was major (MCR) in 93 patients (39%): complete (CCR) in 71 (30%) and
      partial (PCR) in 22 (9%). Patients with an HLA-B27 phenotype had the best
      response rate to IFN-A: 10 of 14 (71%) had an MCR, including eight (57%) with a
      CCR (P=0.02). Patients with HLA-B35, -A3, and -A31 also showed a trend towards a
      higher response rate, whereas patients with HLA-B18 had the lowest response rate
      (MCR 17%). Patients with HLA-B27 and those with HLA-A31 showed a trend for better
      survival, whereas patients with HLA-A2, -B7, or -B18 had a trend for shorter
      survival. We conclude that response to IFN-A in patients with CML may be
      associated with the HLA phenotype. However, a much larger population would be
      required to determine if the impact of HLA phenotype on survival is independent
      of other clinical prognostic features. These findings could be relevant for the
      understanding of immune mechanisms of control of CML and possibly the design of
      immune therapy for this disease.

PMID- 9557602
TI  - The impact of age on outcome in lymphoblastic leukaemia; MRC UKALL X and XA
      compared: a report from the MRC Paediatric and Adult Working Parties.
AB  - The purpose of the study was to examine the influence of age on outcome in a
      large cohort of children and adults with lymphoblastic leukaemia who were treated
      on two similar trials. Factors influencing outcome were examined in 2204 patients
      aged over 1 year treated between 1985 and 1992 on the parallel Medical Research
      Council Trials UKALL X and XA, for children and adults, respectively. There was a
      progressive worsening in survival with increasing age from 85% (95% CI 83-87) at
      5 years for children aged 1-9 to 24% (CI 17-31) for patients over 40. Induction
      failures, deaths in remission and bone marrow relapses increased significantly
      with age. Analysis of clinical and biological features showed dominance of early
      B-ALL in childhood and increasing incidence of the Ph' chromosome with age. Over
      80% of eligible children, but a much lower proportion of adults especially those
      over 40, was entered. Compliance was stricter in the paediatric trial but most
      deviations in adults involved giving more treatment. Analysis of results in a
      proportional hazards model confirmed the overwhelming independent influence of
      age; with all other factors equal a 10 year old had half the risk of treatment
      failure of a 20 year old and a 44 year old double the risk. Selective entry to
      therapeutic trials and increased treatment-related toxicity are features of adult
      ALL but age itself remains a dominant prognostic factor. While improved
      supportive care and refinements of conventional therapy may have some effect on
      prognosis, new understandings and treatment approaches to adult ALL are needed.

PMID- 9557603
TI  - Comparative genomic hybridization as part of a new diagnostic strategy in
      childhood hyperdiploid acute lymphoblastic leukemia.
AB  - The detailed definition of karyotype changes associated with hyperdiploid acute
      lymphoblastic leukemia (ALL) is a precondition for their exploitation in minimal
      residual disease studies with fluorescence in situ hybridization analysis (FISH).
      In addition, certain karyotype patterns may have different prognostic
      implications. We have therefore used comparative genomic hybridization (CGH) to
      analyze the quantitative karyotype abnormalities in 14 cases of hyperdiploid ALL
      and correlated the results with those obtained by flow cytometry and conventional
      cytogenetic analyses. Despite an overall good agreement between the karyotypes
      obtained by classical banding techniques and CGH, we came across at least one
      karyotype discrepancy per case. Clarification of the discordant findings with
      fluorescence in situ hybridization (FISH) showed that all stem lines had been
      correctly defined by CGH. In eight cases, however, cytogenetic analyses revealed
      structural abnormalities that were undetectable by CGH. The other discrepancies
      were mainly due to a cytogenetic misinterpretation of similar sized and shaped
      chromosomes. Based on these findings we present a new diagnostic strategy for
      childhood ALL that includes flow cytometry and classical cytogenetics as well as
      CGH for the analysis of aneuploid cases and FISH to resolve the unavoidable
      discrepancies.

PMID- 9557604
TI  - Refractory anemia with severe dysplasia: clinical significance of morphological
      features in refractory anemia.
AB  - Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous
      diseases regarding their morphology, clinical features and survival. We proposed
      the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal
      dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone
      marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils
      > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA
      patients. RAminiD is defined as RA cases other than RASD. After the
      reclassification of 58 primary RA patients, the group was composed of 45 RAminiD
      and 13 RASD patients. The blast percentage in the BM and the frequency of
      cytogenetic abnormalities observed in the RASD patients were intermediate between
      those in the RAminiD and RAEB patients. The analysis of survival curves revealed
      differences among the three groups; the RASD patients had lower survival
      probabilities than those of the RAminiD group, and significantly higher
      probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs
      RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset
      of RA with an unfavorable clinical outcome.

PMID- 9557605
TI  - Localization of Fas and Fas ligand in bone marrow cells demonstrating
      myelodysplasia.
AB  - Frequent apoptosis in the bone marrow of patients with myelodysplastic syndromes
      (MDS) was demonstrated on frozen sections using the terminal deoxytransferase
      (TdT)-mediated dUTP nick end labeling (TUNEL) method. The overall mean percentage
      of TUNEL-positive cells was about 17% in the bone marrow of MDS, while bone
      marrow from control cases exhibited a mean of 3.4% (P < 0.001). To elucidate the
      mechanism of apoptosis in bone marrow cells of MDS, the expression of Fas antigen
      and Fas ligand (FasL) was examined by RT-PCR and immunohistochemistry. All MDS
      cases showed expression of Fas mRNA (12/12) and most exhibited an expression of
      FasL mRNA (10/12) by RT-PCR. Basically, control cases did not show positive
      signals for Fas and FasL mRNA, however, a very weak band was detected in three
      cases (3/10) for Fas and in one case (1/10) for FasL mRNA by RT-PCR.
      Immunohistochemical examination revealed positive staining for Fas (11/12) and
      FasL (12/12) in the bone marrow of MDS, while all the bone marrow samples from
      control cases were negative for anti-Fas (0/15) and for anti-FasL (0/15)
      antibody. Double staining clarified that TUNEL-positive apoptotic cells expressed
      Fas antigen on the cell surface, although not all Fas-positive cells were TUNEL
      positive. The Fas-positive cells of MDS bone marrow included hematopoietic cells
      expressing CD34 antigen, neutrophil elastase, a marker for myeloid series of
      cells, or glycophorin A, a marker for erythroid cells. However, CD68-positive
      cells which were macrophage lineage cells, did not express Fas antigen strongly.
      In contrast, positive staining for FasL was detected in hematopoietic cells and
      CD68-positive cells in the bone marrow of MDS. These results suggest that the Fas
      FasL system plays an important role in inducing apoptosis in the bone marrow of
      MDS and works in an autocrine (hematopoietic cell-hematopoietic cell interaction)
      and/or paracrine (hematopoietic cell-stromal cell interaction) manner.

PMID- 9557606
TI  - Lymphotoxin-alpha is an autocrine growth factor for chronic lymphocytic leukemia
      B cells.
AB  - Lymphotoxin-alpha (LT), also called TNF-beta, which belongs to the 'TNF family'
      was originally isolated from a lymphoblastoid cell line. LT enhances the
      proliferation of activated B cells and augments B cell proliferation induced by
      IL-2. It functions as an autocrine growth factor for EBV-infected B cell lines
      and has been implicated in the pathogenesis of B cell malignancies. We tested the
      expression of LT mRNA in B-CLL and found that LT was expressed in highly purified
      leukemic cells in 11 out of 11 patients examined. Regulation of expression of LT
      mRNA is aberrant in B-CLL cells, since LT mRNA expression was not detected in
      fresh peripheral blood mononuclear cells or B cells identified in seven out of
      seven normal individuals. In addition, LT mRNA expression was detected for up to
      6 days in purified unstimulated in vitro cultures of B-CLL cells.
      Glucocorticosteroids, that have been effectively used in the treatment of
      lymphoid malignancies, were added to the cultures and abrogated the LT mRNA
      expression after an incubation time of 12 h. Addition of recombinant LT to
      cultures increased proliferation of B-CLL cells while proliferation of these
      cells was inhibited by antisense oligonucleotides against LT mRNA. B-CLL cells
      cultured with LT antisense oligonucleotides (asLT) as well as glucocorticoid
      treated cells showed reduced viability and a DNA fragmentation ladder
      characteristic of apoptosis suggesting a relationship between down-regulation of
      LT mRNA expression and the induction of apoptosis. These studies support the role
      of LT in the growth regulation and development of B-CLL cells.

PMID- 9557607
TI  - Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid
      leukemia.
AB  - Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The
      CD4+CD8+ double-positive (DP) phenotype is seen in a few cases. Since DP
      generally occurs in thymic T cells, whether the DP T leukemia cells represent
      thymic or peripheral T cells has been a matter of controversy. To address this
      issue, we studied phenotypical features in eight cases of DP T cell leukemia.
      Thymic DP T cells and peripheral CD8+ T cells have CD8 of alphabeta subunit,
      while CD8alphaalpha is induced in CD4+ T cells on activation with IL-4. We found
      that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim
      expression of CD8alphaalpha, identical to the phenotype on IL-4-activated DP-T
      cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high
      levels of IL-4. These findings suggest that they may be derived from peripheral
      CD4+ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed
      CD8alphaalpha, suggestive of an activated peripheral T cell origin. One case
      expressed CD8alphaalpha dim and IL-4 mRNA, while the other two cases expressed no
      IL-4 mRNA and showed CD8alphaalpha bright phenotype, features not found in normal
      T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL)
      expressed CD8alphabeta. The DP phenotype is relatively common in T-PLL, and
      CD4+CD8alphabeta+ is characteristic of thymic T cells. The DP T-PLL cells did not
      express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down
      regulated at the late stage of thymic T cell development. On the basis of these
      findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T
      cells differed for each entity and appeared to correlate with minor normal DP T
      cell population.

PMID- 9557608
TI  - Drug resistance in multiple myeloma: cyclosporin A analogues and their
      metabolites as potential chemosensitizers.
AB  - The malignant clone in myeloma is not eradicated by chemotherapy. Cyclosporins
      inhibit drug transport mechanisms, particularly the multidrug transporter p
      glycoprotein 170, leading to their use as chemosensitizers. In myeloma,
      clonotypic blood B cells represent the major drug-resistant subset. This study
      compares the ability of cyclosporin A analogues and metabolites to inhibit
      cellular transporter(s) in myeloma and normal B cells in vitro, and evaluates
      their potential role in vivo. Cyclosporin A (CsA), CsG, PSC 833 or SDZ 280-446,
      and primary CsA and CsG metabolites, were tested for their ability to inhibit
      drug transport mechanisms of ex vivo malignant B cells from 81 patients with
      multiple myeloma as compared to B cells from normal donors, as measured by the
      export of the dye rhodamine 123 (Rh123) using multiparameter flow cytometry. The
      majority of myeloma B and normal B cells had efficient transporter function as
      measured by their CsA-sensitive export of Rh123. CsA and CsA analogues mediated
      efficient inhibition of this transport. Inhibition of dye transport by normal B
      cells required an approximately six-fold greater concentration of the synthetic
      peptolide SDZ 280-446 than was needed to optimally inhibit transport by myeloma B
      cells. PSC 833 and CsG were inhibitory at concentrations approximately five-fold
      lower than were required for CsA. Assessment of inhibitory potency in vivo
      indicated that the in vivo chemosensitizer levels of CsA and PSC 833 exceeded the
      transporter inhibitory concentration by four- and 20-fold respectively. In vivo,
      cyclosporins are rapidly and almost completely converted to metabolites. AM1 and
      AM4N, primary metabolites of CsA, mediated inhibition of transport, as did CsG
      metabolites GM1, GM4N and GM9. AM1 and GM9 are known to reach steady-state in
      vivo levels that exceed the inhibitory concentration identified here by 1.1- to
      1.9-fold. Thus, cyclosporin metabolites, which accumulate in the blood during
      infusion of CsA and other cyclosporins, are shown here to be effective
      chemosensitizers for normally drug-resistant myeloma cells in vitro. Cyclosporin
      metabolites are considered to be less toxic than the parent drugs, suggesting
      that novel chemosensitization strategies designed to minimize concentrations of
      parent drug and maximize accumulation of primary metabolites in vivo may optimize
      cytotoxicity to the malignant clone in myeloma.

PMID- 9557609
TI  - Identification of a commonly deleted region at 17p13.3 in leukemia and lymphoma
      associated with 17p abnormality.
AB  - Fluorescence in situ hybridization (FISH) was performed in 17 myeloid leukemia
      patients and seven lymphoid leukemia/ lymphoma patients who exhibited chromosomal
      abnormalities on the short arm of chromosome 17, in order to detect a commonly
      deleted region on chromosome band 17p13. Twenty-four leukemia/lymphoma patients
      studied cytogenetically at our institution over a period of 10 years had
      detectable 17p abnormalities such as translocation (six patients), addition (11
      patients) and deletion of 17p13 (seven patients). A 17p abnormality was the only
      abnormality present in three patients. Most of the patients had additional
      complex cytogenetic abnormalities. The diagnosis was acute myeloid leukemia (AML)
      in 10 patients, two each with chronic myeloid leukemia (CML), acute lymphoblastic
      leukemia (ALL), chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome
      (MDS) and the remaining three with malignant lymphoma (ML). Seven cosmid probes
      (D17S34, cCI17-624, cCI17-453, D17S379, cCI17-636, cCI17-732 and TP53) which
      mapped on 17p13 were used to analyze the allelic deletion. Eighty percent (19 out
      of 24) of the informative leukemia patients exhibited allelic loss in 17p13.3 at
      cC17-624. The smallest region of an overlapping deletion was observed on
      chromosome band 17p13.3 between cCI17-624 and cCI17-453. Patients with
      translocation involving 17p also showed deletion at cCI17-624 and cCI17-453. We
      hypothesize that this region contains a novel tumor suppressor gene(s) that is
      involved in leukemogenesis.

PMID- 9557610
TI  - Acquisition of the Ph chromosome and BCR-ABL fusion product in AML-M2 and t(8;21)
      leukemia: cytogenetic and FISH evidence for a late event.
AB  - A patient with the M2 subtype of AML who had a 45,X,-X,t(8;21) karyotype at
      diagnosis was found to have the Ph chromosome in one out of 37 evaluated cells 18
      months after the initial diagnosis. Interphase FISH studies utilizing a BCR-ABL
      dual-color probe did not detect a fusion product 4 months prior to the appearance
      of one Ph-positive cell. Nineteen months post diagnosis and 5 months after
      clinical relapse all evaluated cells had the Ph chromosome in a clone
      characterized by t(8;21). These observations suggest that late appearing Ph is a
      secondary event which may be either therapy-related or consistent with one of the
      later events in a multistep pathogenesis of AML.

PMID- 9557611
TI  - Characterization of proteins binding the 3' regulatory region of the IL-3 gene in
      IL-3-dependent and autocrine-transformed hematopoietic cells.
AB  - Previously we documented the prolongation of the IL-3 mRNA half-life in an
      autocrine-transformed cell line. This cell line has an intracisternal type A
      particle transposition in the IL-3 mRNA 3' untranslated region which displaced
      four out of six AUUUA motifs involved in IL-3 mRNA destabilization. In this
      study, the proteins binding to the IL-3 mRNA AU-rich elements (ARE) were
      examined. Specific protein binding was detected to the wild-type IL-3 ARE region
      which contained 6 AUUUA motifs (AU6). In contrast, no binding was detected to the
      mutated IL-3 ARE region which contained only two AUUUA motifs (AU2). Proteins
      with apparent molecular weights of 36, 40, 43, 46, 55, 57, 68 and 95 kDa were
      bound to AU6 motif. The hnRNP C and AUF-1 (hnRNP D) proteins were determined to
      be two of the IL-3 ARE binding proteins. Incubation of protein extracts with
      antibodies to hnRNP C and AUF-1 significantly decreased the protein binding to
      the IL-3 ARE. Treatment of IL-3 dependent cells with calcium ionophores
      eliminated the proteins binding to the ARE in wild-type IL-3-dependent FL5.12
      cells and also resulted in the accumulation of IL-3 mRNA transcripts with a long
      half-life. These results indicated that there was a specific complex which bound
      the IL-3 mRNA 3' ARE. Mutations which truncate the IL-3 ARE eliminate the ability
      of proteins to bind this regulatory region and can result in autocrine
      transformation due to the presence of IL-3 mRNA transcripts with a long half
      life.

PMID- 9557612
TI  - Antisense sequences of the nbl gene induce apoptosis in the human promyelocytic
      leukemia cell line HL-60.
AB  - Apoptosis is induced by the transcriptional inhibitor actinomycin D (Act D) in
      various cell types, particularly many leukemic cell lines such as HL-60. A common
      feature of these cell lines is their high constitutive expression level of the
      nbl gene, which was originally isolated by virtue of its abundance in a Namalwa
      Burkitt lymphoma cDNA library. In contrast, cell lines which constitutively
      express nbl at low levels appear not to undergo typical apoptotic death in
      response to Act D. Apoptotic induction by Act D in cells which normally express
      nbl at high levels was found in this study to be closely associated with a
      decline in nbl mRNA levels, raising the possibility that apoptosis could be
      induced by lowering nbl expression levels in such cells. Transient expression of
      nbl antisense sequences in HL-60 cells decreased cell viability, and induced
      typical apoptotic morphology such as cell shrinkage, chromatin condensation and
      nuclear fragmentation. Incubation with nbl antisense oligomers also induced
      similar features in HL-60 cells and in another high nb-expressing cell line,
      Jurkat, but had little effect in HepG2 cells which constitutively express nbl at
      low levels. These findings suggest that lowering constitutively high levels of
      nbl expression can induce apoptosis.

PMID- 9557613
TI  - V-myc in a simple, single gene retroviral vector causes rapid induction of
      leukemia and concomitant apoptosis following bone marrow transplantation.
AB  - We have previously developed an in vivo model of leukemogenesis utilizing mice
      reconstituted with genetically modified bone marrow cells. Based on those
      studies, a new single gene retroviral vector has been engineered which
      efficiently transfers v-myc into immature murine bone marrow cells. All
      reconstituted mice developed leukemia with a short latency period (5-11 weeks).
      In addition to hyperproliferation associated with elevated levels of PCNA,
      extensive apoptosis was also observed in all leukemic animals with p53
      accumulating in the apoptotic cells. Whereas bax encoded protein, an effector of
      p53 apoptotic activity was detected in apoptotic cells, p21Waf1 protein, a
      potential mediator of p53 growth suppression was not detected in these cells
      suggesting that v-myc-induced apoptosis was independent of the ability of p53 to
      induce p21Waf1. These results indicate that apoptosis, a part of the cellular
      response to v-myc expression, does not prevent leukemia development and that
      hyperproliferation rather than abrogation of oncogene-induced apoptosis appears
      to be a critical event in v-myc-induced leukemia.

PMID- 9557614
TI  - Characterization of the chimeric retinoic acid receptor RARalpha/VDR.
AB  - The chimeric receptor, RARalpha/VDR, contains the DNA-binding domain of the
      retinoic acid receptor (RARalpha) and the ligand-binding domain of the vitamin D
      receptor (VDR). The ligand-binding properties of RARalpha/VDR are equivalent to
      that of VDR, with an observed Kd for 1alpha,25 dihydroxy-vitamin D3 (D3) of 0.5
      nM. In CV-1 cells, both RARalpha and RARalpha/VDR induce comparable levels of
      ligand-mediated transcriptional activity from the retinoic acid responsive
      reporter gene, beta(RARE)3-TK-luciferase, in the presence of the ligand predicted
      from the receptor ligand-binding domain. Two chimeric RAR receptors were
      constructed which contained the ligand-binding domain of the estrogen receptor
      (ER): RARalpha/ER and ER/RARalpha/ER. Both RARalpha/ER and ER/RARalpha/ER bind
      beta-estradiol with high affinity, and are transcriptionally active only from
      palindromic RAREs (TREpal and/or (TRE3)3). Only RARalpha/VDR matched in kind and
      degree the functional characteristics of RARalpha: (1) maximally active from the
      beta(RARE); (2) moderately active from the TREs; (3) inactive from the retinoic X
      receptor response elements (RXREs) ApoA1 and CRBP II; (4) forms heterodimers with
      RXRalpha; and (5) binds to the betaRARE. F9 embryonal carcinoma cell lines were
      generated which express RARalpha/VDR mRNA (F9RARalpha/VDR cells) and compared
      with F9 wild-type (F9-Wt) cells, which do not express VDR mRNA. Treatment with
      all-trans retinoic acid (tRA) inhibits cell growth and induces the
      differentiation morphology in both F9-Wt and F9-RARalpha/VDR cells; whereas,
      treatment with D3 is similarly effective only for F9-RARalpha/VDR cells. It is
      concluded RARalpha/VDR is an useful 'tool' to pinpoint, or to augment
      transcription from RAREs in gene pathways controlled by RAR without inhibiting
      the retinoid responsiveness of endogenous RARs.

PMID- 9557615
TI  - Terminal megakaryocytic differentiation of TF-1 cells is induced by phorbol
      esters and thrombopoietin and is blocked by expression of PML/RARalpha fusion
      protein.
AB  - We have analyzed the differentiation program of growth factor-dependent TF-1
      erythroleukemia cells as well as clones with inducible expression of the APL
      specific PML/RARalpha protein. We have shown that TF-1 cells may be induced to
      megakaryocytic differentiation by phorbol ester (phorbol dibutyrate, PDB)
      addition, particularly when combined with thrombopoietin (Tpo). RT-PCR studies
      showed that Tpo induces Tpo receptor (TpoR or c-mpl), whose expression was
      further potentiated by PDB addition. When the cells are induced with both PDB and
      Tpo erythropoietin receptor (EpoR) expression was inhibited. In the absence of
      Zn2+-induced PML/RARalpha expression, PDB and Tpo induced megakaryocytic
      differentiation of TF-1 MTPR clones as observed in 'wild-type' TF-1 cells.
      Conversely, when PML/RARalpha expression was induced by Zn2+, PDB and Tpo
      treatment of these clones caused only a reduced level of megakaryocytic
      differentiation. These observations indicate that: (1) TF-1 cells as well as
      other erythroleukemic cells, possess the capacity to differentiate to
      megakaryocytic cells when grown in the presence of protein kinase (PKC)
      activators and more efficiently when combined with Tpo; (2) the PML/RARalpha gene
      has a wide capacity to interfere with the program of hematopoietic
      differentiation, including megakaryocytic differentiation. Finally, we also
      observed that PML/RARalpha expression in TF-1 cells induces an up-modulation of
      interleukin-3 receptor, c-kit and c-mpl, a phenomenon which may offer these cells
      a growth advantage.

PMID- 9557616
TI  - The low cycling status of mobilized peripheral blood CD34+ cells is not
      restricted to the more primitive subfraction.
AB  - Mobilized peripheral blood progenitor cells (PBPC) have been shown to differ
      qualitatively from bone marrow (BM) progenitors. The released progenitor cells
      are predominantly in G0/G1 and show a relatively high percentage of rhodamine
      dull cells. Within the BM these last two features are characteristic of the more
      primitive progenitors. Although the mobilized PB cells can give rise to long-term
      repopulation and thus contain stem cells, the frequency of stem cells is not much
      higher if long-term initiating cell (LTC-IC) assays are used. To determine
      whether quiescent stem cells are selectively released or the low-cycle status of
      PB progenitors is related to the release from the BM microenvironment, the cell
      cycle status and rhodamine content in the PB and BM during mobilization were
      studied and compared with steady-state BM. More differentiated and more primitive
      progenitors were separated based on differentiation markers and cloned in single
      cell assay. In mobilized PB 54% of the CD34+ cells (n=5) were rhodamine dull
      compared to 22% in steady-state BM (P=0.014) [n=6]. The percentage of CD34+ cells
      in the S/G2M phases of the cell cycle was 2.1% in the mobilized PB (n=11), and
      18% in steady-state BM (n=11) [P=0.002]. During mobilization the fraction of
      cells in the S/G2M phase of the cell cycle was 16% in BM (n=7), similar to steady
      state BM (P=0.34). The released progenitors represented a selection of BM
      progenitors, with significantly more primitive progenitors (CD34+/13+/33dim) and
      less lymphoid precursors (CD34+/19+). Within the more differentiated
      CD34+113+/33bright, myelomonocytic precursors, both in PB as well as in BM, the
      percentage S/G2M was relatively higher than in the CD34+/13+/33dim subfraction:
      in normal BM: median 18% vs 8% (P=0.006) [n=8]; in mobilized PB 3% vs 2% (P=0.03)
      [n=10]; and in BM during mobilization 24% vs 7% (P=0.01) [n=6]. The cycle status
      of mobilized PB progenitors was low both in the primitive and more differentiated
      subfractions. During the mobilization period the BM progenitors are cycling as in
      steady-state BM. The low-cycle status of the mobilized PB progenitors may be
      related to the loss of contact with the micro-environment.

PMID- 9557617
TI  - Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I
      associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical,
      pathological and immunovirological study of 14 cases and a review of the African
      ATL cases.
AB  - Cutaneous T cell lymphomas (CTCL) are rare lymphoproliferative diseases, which
      are frequently suspected to be of viral origin. As very few data were available
      concerning cutaneous T cell lymphomas in tropical Africa, we undertook a
      clinical, histopathological, immunological and viro-molecular study of patients
      with a clinical diagnosis of cutaneous lymphoma, in Bamako, Mali. While prior to
      this study, no case of CTCL had been reported in this country, 14 patients (five
      women, nine men; mean age 58 years) with a diagnosis of cutaneous lymphoma were
      seen over a period of 30 months (1992-1994) in the only dermatological department
      in Mali. Clinically, the most frequent pattern was an infiltrated erythrodermia
      similar to Sezary syndrome. Nodular lesions and/or plaques were rarely observed.
      All these cutaneous tumors were T cell lymphoproliferations, only one expressing
      the CD8+ antigen. A comprehensive analysis of all the available data permitted
      characterization of three cases of adult T cell leukemia/lymphoma (ATL)
      associated with HTLV-I (one definitive case, of leukemic type, with demonstration
      of clonal integration of HTLV-I proviral genome and two probable ATL cases),
      three cases of Sezary syndrome (SS), two cases of mycosis fungoides (MF) and five
      cases of pleomorphic cutaneous lymphoma. In one case, the differentiation between
      MF and pleomorphic cutaneous lymphoma could not be established. HTLV-I
      serological and/or molecular markers were restricted to the three ATL cases. From
      the unique definitive ATL case, a T cell line was established from culture of
      peripheral blood mononuclear cells and sequence analysis of the env gene and the
      U3-LTR region demonstrated that the virus present in this patient belonged to the
      cosmopolitan subtype A. Thus, we report here the first evidence of HTLV-I
      infection and associated ATL in Mali. This is the second ATL case described for
      the whole Sahelian region (one ATL of the lymphoma type was reported previously
      in a Mauritanian patient). Furthermore, we demonstrate that the main types of
      CTCL described in Europe and North America are also present in this African area
      and that the prevalence of these diseases is greatly underestimated in such
      regions. Furthermore, no association was observed between HTLV-I/II infection and
      SS, MF or pleomorphic cutaneous lymphoma in Mali in contrast to other studies.

PMID- 9557618
TI  - Quality of life in adult patients with acute myeloid leukemia receiving intensive
      and prolonged chemotherapy -- a longitudinal study.
AB  - Intensification of treatment for acute myeloid leukemia (AML) in adult patients
      resulted in a substantial improvement in long-term prognosis. Therefore, the
      assessment of quality of life (QL) of patients undergoing treatment is of growing
      interest. This study was designed to evaluate QL in patients with AML treated
      according to the protocol of the German AML-Cooperative Group (Munster, Germany).
      The EORTC QLQ-C 30 questionnaire was used to analyze QL throughout therapy,
      evaluating defined specific parameters at 12 different time-points. Sixty-one
      patients were recruited within the first 30 months of the study. Those 28
      patients who have completed the course of inpatient treatment (n=28) are
      evaluated for changes in the conceptually distinct QL domains: Physical
      Functioning (P<0.001), Role Functioning (P=0.001), Emotional Functioning (P <
      0.001) and Social Functioning (P=0.007) improve significantly from beginning of
      chemotherapy to the end of inpatient treatment. Individual assessment of Global
      Health Status and Subjective QL improves significantly over the same time (P<
      0.001). At the end of inpatient treatment patients suffer significantly less from
      fatigue, nausea/emesis, loss of appetite and sleep disturbance (P < 0.001).
      Although most patients with AML eventually relapse, the evaluation of QL in
      patients undergoing treatment shows that subjective benefit outweighs the adverse
      effects of antileukemic therapy.

PMID- 9557619
TI  - Contrast in cytokine expression between patients with monoclonal gammopathy of
      undetermined significance or multiple myeloma.
AB  - We investigated whether differences in IL-6 and IL-1beta expression could be
      detected in monoclonal plasma cells from patients with MGUS or MM. Expression of
      IL-6 and IL-1beta in bone marrow cells was determined using cell sorting to
      enrich for plasma cells followed by reverse transcriptase/polymerase chain
      reaction (RT/PCR). Nineteen patients (six MGUS, two primary amyloid (AL), 11 MM)
      were studied. IL-6 mRNA expression was detectable in the sorted CD38+/CD45-
      plasma cell populations from 0/6 MGUS, 0/2 AL and 5/11 MM patients. All five MM
      patients with autocrine IL-6 expression demonstrated an elevated plasma cell
      labeling index. IL-1beta mRNA was detectable in the sorted CD38+/CD45- plasma
      cell populations from 1/6 MGUS, 0/2 AL and 10/11 MM patients. In situ
      hybridization (ISH) confirmed that the IL-1beta producing cells were plasma
      cells. In conclusion, autocrine production of IL-6 parallels a high labeling
      index and aberrant expression of IL-1beta correlates with the diagnosis of MM.
      Follow-up of IL-1beta-positive MGUS patients will determine whether aberrant
      expression of IL-1beta will predict those MGUS patients that will eventually
      progress to MM.

PMID- 9557620
TI  - Characterization of the immunoglobulin light chain variable region gene expressed
      in multiple myeloma.
AB  - We studied the organization, diversification and clinical significance of the
      immunoglobulin light chain (IgL) variable region genes expressed in 17 kappa
      chain and 16 lambda-chain producing multiple myeloma (MM) samples. The V genes
      from 31 MM samples had over 84.9% homology to the known germline Vkappa/lambda
      genes, whereas one Vkappa and one Vlambda gene had only 75.5% and 65.9% homology,
      respectively. While all five Jkappa segments were equally used, only Jlambda-1 or
      Jlambda-2/3 was used among seven Jlambda segments. N nucleotide addition was
      found at two Vkappa-Jkappa and five Vlambda-Jlambda junctions. The lambda-chain
      complementarity determining region (CDR)-3 was longer and more variable than the
      kappa-chain CDR-3 mainly due to junctional flexibility of Vlambda and Jlambda
      segments. Somatic mutations were more frequent in the Jlambda than the Jkappa
      segments, and were distributed in the CDR-3 as well as the frame work region
      (FWR)-4. Those of the Jkappa segments, however, were limited to FWR-4. In FWR-4,
      replacement mutations were clustered at codon 106 of kappa-chain and 103 of
      lambda-chain. Thus nucleotide mutation or conservation was dependent on position,
      indicating a structural necessity of IgL for the development of myeloma cells in
      addition to a non-random distribution of mutations. There was no characteristic
      IgL sequence according to the isotype of M-protein, clinical stage or renal
      complication.

PMID- 9557621
TI  - Malignant plasma cell lines express a functional CD28 molecule.
AB  - The function of CD28 molecules that are present on malignant plasma cells of
      human myeloma cell lines (HMCL) was studied. First, myeloma cells expressed a
      similar density of CD28 antigen to that of normal T cells. The myeloma CD28
      molecules were able to bind B7-Ig molecules as well as L cells transfected with a
      B7-1 cDNA, and anti-CD28 mAb inhibited the binding. Myeloma cells did not express
      B7-1 antigens but a low density of B7-2 antigens. The myeloma B7-2 molecules of
      two HMCL were able to bind CTLA-4 protein. No autocrine CD28:B7-2 activation
      could be evidenced as we found no spontaneous binding of the p85 subunit of PI-3
      kinase to CD28 molecules. In addition, a blocking anti-CD28 mAb did not affect
      the IL-6-dependent or autonomous proliferation of the HMCL. The activation of
      myeloma CD28 molecules with or without TPA stimulation did not affect the
      proliferation, survival, differentiation, expression of activation antigens and
      cytokine receptors or cytokine production of myeloma cells. However, the
      triggering of myeloma CD28 molecules by B7-1 transfectant cells resulted in
      binding of the p85 subunit of PI-3 kinase to CD28 molecules as previously shown
      for T cell CD28 molecules. This expression of a large density of CD28 molecules
      able to bind B7 molecules might contribute to a downregulation of the immune
      control of myeloma cells.

PMID- 9557622
TI  - Profound abnormality of the B/T lymphocyte ratio during chemotherapy for
      pediatric acute lymphoblastic leukemia.
AB  - The fluorescence-activated cell sorter (FACS) was utilized to phenotype
      lymphocyte compartments in children receiving intensive chemotherapy for acute
      lymphoblastic leukemia (ALL). Sixteen patients (eight males and eight females) of
      diverse ages, risks of relapse, and within weeks 7-53 of maintenance/continuation
      chemotherapy treatment were arbitrarily selected for study. All 16 patients had
      profound B cell lymphopenia. In contrast, T cell numbers were often normal or
      marginally low, and accounted for up to 98% of the lymphocyte populations. No
      abnormality in T cell phenotypes could be demonstrated. Due to the highly skewed
      B/T lymphocyte ratios in these ALL patients, the absolute white blood cell counts
      and lymphocyte percentages were not predictive of the underlying B cell
      lymphopenia. Patients were also tested for serum immunoglobulin levels and most
      had abnormally low IgG and IgM. None of four patients immunized with the 1996
      1997 influenza virus vaccine seroconverted to at least two vaccine antigens as
      compared to 10 of 10 healthy, age-matched controls. In total, these data
      highlight for the first time the profound abnormality of the B/T lymphocyte ratio
      in patients during treatment for ALL, and argue for consideration of B cell
      targeted immunotherapy.

PMID- 9557624
TI  - Use of the comet test in the evaluation of multidrug resistance of human cell
      lines.
AB  - The comet test is a reported method for measuring DNA damage in individual
      mammalian cells. In the present report, the ability of this test to detect
      multidrug resistance (MDR) was evaluated. For this purpose, two human leukemia,
      well-characterized parental cell lines, HL60 and CEM, and their derived multidrug
      resistant cells, HL60/DNR and CEM/VBL, were cultured with or without different
      anti-cancer agents. To evaluate the comet test, two DNA-damaging agents were
      used: daunorubicin (DNR), which is involved in MDR, and ambamustine (AMBA), which
      is independent from MDR. Moreover, in order to evaluate the specificity of the
      comet test, the activity of vinblastine (VBL), an MDR-related, DNA-independent
      anti-cancer drug, was also tested. Finally, the specificity of the comet test in
      detecting MDR was confirmed by culturing parental or resistant cells with DNR
      with or without the revertant agent verapamil (VER). Results confirm that the
      comet test is able to predict cellular chemoresistance when DNA damaging agents
      are tested. Finally, experiments on the role of the comet test in evaluating
      certain aspects of DNA repair are discussed.

PMID- 9557623
TI  - Demonstration of clonality in neutrophils using FISH in a case of chronic
      neutrophilic leukemia.
AB  - A patient previously diagnosed with chronic neutrophilic leukemia (CNL) was
      studied using fluorescent in situ hybridization (FISH) to determine clonality of
      neutrophils. By cytogenetic studies the patient's blood and bone marrow had an
      11q14 deletion and were negative for the Philadelphia (Ph) chromosome. FISH was
      performed on peripheral blood smears using probes for the bcr/abl translocation
      and a probe for 11q23 (MLL). The patient's white blood cells were negative for
      the bcr/abl translocation; neutrophils and eosinophils, but not lymphocytes, were
      monosomic for the 11q23 probe indicating a clonal population within the
      neutrophil population.

PMID- 9557625
TI  - More on purine analog-induced apoptosis in B cell chronic lymphocytic leukemia.

PMID- 9557626
TI  - Complement values in B chronic lymphocytic leukemia: prognostic significance and
      correlation with cell maturation stage.

PMID- 9557628
TI  - Identification and characterization of a porcine torovirus.
AB  - A porcine torovirus (PoTV) was identified and characterized; it is a novel member
      of the genus Torovirus (family Coronaviridae, order Nidovirales), closely related
      to but clearly distinct from the already recognized equine torovirus (ETV) and
      bovine torovirus (BoTV) representatives. Immunoelectron microscopy of feces from
      piglets revealed elongated, 120- by 55-nm particles which were recognized by a
      torovirus-specific antiserum. Amplification by reverse transcriptase (RT) PCR
      with primers designed to detect conserved regions (on the basis of the genomes of
      BoTV strain Breda and ETV strain Berne) resulted in the identification of the 489
      bp nucleocapsid gene, encoding a 18.7-kDa protein. The sequence identity in this
      region between PoTV and both ETV and BoTV was only about 68%, whereas the latter
      two show 81% identity. Neutralizing antibodies directed against ETV were found in
      sera of adult and young pigs. In all 10 herds sampled, seropositive animals were
      present, and 81% of randomly selected adult sows possessed antibodies. A
      longitudinal study with RT PCR showed that piglets shed virus in the feces for 1
      or more days, starting 4 to 14 days after weaning.

PMID- 9557630
TI  - Switch to unusual amino acids at codon 215 of the human immunodeficiency virus
      type 1 reverse transcriptase gene in seroconvertors infected with zidovudine
      resistant variants.
AB  - Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in
      successive plasma samples from eight seroconverting patients infected with virus
      bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV)
      resistance. At baseline, additional mutations associated with ZDV resistance were
      detected. Three patients had the M41L amino acid change, which persisted. Two
      patients had both the D67N and the K70R amino acid substitutions; reversion to
      the wild type was seen at both positions in one of these patients and at codon 70
      in the other one. Reversion to the wild type at codon 215 was observed in only
      one of eight patients. Unusual amino acids, such as aspartic acid (D) and
      cysteine (C), appeared at position 215 in four patients during follow-up. These
      variants isolated by coculturing were sensitive to ZDV. Overgrowth of these
      variants suggests that they have better fitness than the original T215Y variant.
      Intraindividual nucleoside substitutions over time were 10 times more frequent in
      codons associated with ZDV resistance (41, 67, 70, 215, and 219) than in other
      codons of the RT domain. The predominance of nonsynonymous substitutions observed
      over time suggests that most changes reflect adaptation of the RT function. The
      variance in sequence evolution observed among patients, in particular at codon
      215, supports a role for chance in the evolution of the RT domain.

PMID- 9557629
TI  - Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is
      determined primarily by occupancy of sites on the virion irrespective of epitope
      specificity.
AB  - We investigated the relative importance of binding site occupancy and epitope
      specificity in antibody neutralization of human immunodeficiency virus (HIV) type
      1 (HIV-1). The neutralization of a T-cell-line-adapted HIV-1 isolate (MN) was
      analyzed with a number of monovalent recombinant Fab fragments (Fabs) and
      monoclonal antibodies with a range of specificities covering all confirmed gp120
      specific neutralization epitopes. Binding of Fabs to recombinant monomeric gp120
      was determined by surface plasmon resonance, and binding of Fabs and whole
      antibodies to functional oligomeric gp120 was determined by indirect
      immunofluorescence and flow cytometry on HIV-infected cells. An excellent
      correlation between neutralization and oligomeric gp120 binding was observed, and
      a lack of correlation with monomeric gp120 binding was confirmed. A similar
      degree of correlation was observed between oligomeric gp120 binding and
      neutralization with a T-cell-line-adapted HIV-1 molecular clone (Hx10). The
      ratios of oligomer binding/neutralization titer fell, in general, within a
      relatively narrow range for antibodies to different neutralization epitopes.
      These results suggest that the occupancy of binding sites on HIV-1 virions is the
      major factor in determining neutralization, irrespective of epitope specificity.
      Models to account for these observations are proposed.

PMID- 9557631
TI  - Activation of caspases in pig kidney cells infected with wild-type and CrmA/SPI-2
      mutants of cowpox and rabbitpox viruses.
AB  - The cowpox virus (CPV) CrmA and the equivalent rabbitpox virus (RPV) SPI-2
      proteins have anti-inflammatory and antiapoptosis activity by virtue of their
      ability to inhibit caspases, including the interleukin-1beta-converting enzyme
      (ICE; caspase-1). Infection of LLC-PK1 pig kidney cells with a CPV CrmA mutant,
      but not with wild-type (wt) CPV, results in the induction of many of the
      morphological features of apoptosis (C. A. Ray and D. J. Pickup, Virology 217:384
      391, 1996). In our study, LLC-PK1 cells infected with CPV delta crmA, but not
      those infected with wt CPV, showed induction of poly(ADP-ribose) polymerase
      (PARP)- and lamin A-cleaving activities and processing of the CPP32 (caspase-3)
      precursor to a mature 18-kDa form. Surprisingly, infection of LLC-PK1 cells with
      either wt RPV (despite the presence of the SPI-2 protein) or RPV delta SPI-2
      resulted in cleavage activity against PARP and lamin A and the appearance of the
      mature subunit of CPP32/caspase-3. The biotinylated specific peptide inhibitor Ac
      Tyr-Val-Lys(biotinyl)-Asp-2,6-dimethylbenzoyloxymethylketone [AcYV(bio)KD-aomk]
      labeled active caspase subunits of 18, 19, and 21 kDa in extracts from LLC-PK1
      cells infected with CPV delta crmA, wt RPV, or RPV delta SPI-2 but not wt CPV.
      Mixed infection of LLC-PK1 cells with wt RPV and wt CPV gave no PARP-cleaving
      activity, and all PARP cleavage mediated by SPI-2 and CrmA mutants of RPV and
      CPV, respectively, could be eliminated by coinfection with wt CPV. These results
      suggest that the RPV SPI-2 and CPV CrmA proteins are not functionally equivalent
      and that CrmA, but not SPI-2 protein, can completely prevent apoptosis in LLC-PK1
      cells under these conditions.

PMID- 9557632
TI  - Human immunodeficiency virus type 1 subtype F reverse transcriptase sequence and
      drug susceptibility.
AB  - We sequenced and phylogenetically analyzed the reverse transcriptase (RT) regions
      of the pol genes of 14 human immunodeficiency virus type 1 (HIV-1) isolates from
      Romanian patients, which were classified as subtype F on the basis of env gene
      structure. The RT sequences showed that the strains clustered phylogenetically
      and were equidistant from other HIV-1 subtypes as shown by the neighbor-joining
      and maximum-likelihood methods, allowing us to define HIV-1 subtype F according
      to the pol classification. The subtype F RT sequences differed from reported
      group M RT sequences by 10.94% (for nucleotides) and 7.6% (for amino acids).
      Phenotypic analysis of subtype F susceptibility to three classes of
      antiretroviral compounds showed an increase in the 50% inhibitory concentration
      of the tetrahydroimidazo[4,5,1-jk] [1,4]-benzodiazepin-2-(1H)-one and -thione
      (TIBO) derivate R82913 for one strain which was naturally resistant to this
      compound. This first report of subtype F pol sequences confirms the perfect
      correlation between the phylogenetic positions determined by env and pol analyses
      and suggests that virus variability might influence the efficacy of
      antiretroviral treatments. This finding warrants a global evaluation of the
      phenotypic and genotypic susceptibility of HIV-1 subtypes to antiretroviral
      drugs.

PMID- 9557633
TI  - Functional role of hepatitis C virus chimeric glycoproteins in the infectivity of
      pseudotyped virus.
AB  - The putative envelope glycoproteins of hepatitis C virus (HCV) likely play an
      important role in the initiation of viral infection. Available information
      suggests that the genomic regions encoding the putative envelope glycoproteins,
      when expressed as recombinant proteins in mammalian cells, largely accumulate in
      the endoplasmic reticulum. In this study, genomic regions which include the
      putative ectodomain of the E1 (amino acids 174 to 359) and E2 (amino acids 371 to
      742) glycoproteins were appended to the transmembrane domain and cytoplasmic tail
      of vesicular stomatitis virus (VSV) G protein. This provided a membrane anchor
      signal and the VSV incorporation signal at the carboxy termini of the E1 and E2
      glycoproteins. The chimeric gene constructs exhibited expression of the
      recombinant proteins on the cell surface in a transient expression assay. When
      infected with a temperature-sensitive VSV mutant (ts045) and grown at the
      nonpermissive temperature (40.5 degrees C), cells transiently expressing the E1
      or E2 chimeric glycoprotein generated VSV/HCV pseudotyped virus. The resulting
      pseudotyped virus generated from E1 or E2 surprisingly exhibited the ability to
      infect mammalian cells and sera derived from chimpanzees immunized with the
      homologous HCV envelope glycoproteins neutralized pseudotyped virus infectivity.
      Results from this study suggested a potential functional role for both the E1 and
      E2 glycoproteins in the infectivity of VSV/HCV pseudotyped virus in mammalian
      cells. These observations further suggest the importance of using both viral
      glycoproteins in a candidate subunit vaccine and the potential for using a
      VSV/HCV pseudotyped virus to determine HCV neutralizing antibodies.

PMID- 9557634
TI  - Cross-reactions between the cytotoxic T-lymphocyte responses of human
      immunodeficiency virus-infected African and European patients.
AB  - The great variability of protein sequences from human immunodeficiency virus
      (HIV) type 1 (HIV-1) isolates represents a major obstacle to the development of
      an effective vaccine against this virus. The surface protein (Env), which is the
      predominant target of neutralizing antibodies, is particularly variable. Here we
      examine the impact of variability among different HIV-1 subtypes (clades) on
      cytotoxic T-lymphocyte (CTL) activities, the other major component of the
      antiviral immune response. CTLs are produced not only against Env but also
      against other structural proteins, as well as some regulatory proteins. The
      genetic subtypes of HIV-1 were determined for Env and Gag from several patients
      infected either in France or in Africa. The cross-reactivities of the CTLs were
      tested with target cells expressing selected proteins from HIV-1 isolates of
      clade A or B or from HIV type 2 isolates. All African patients were infected with
      viruses belonging to clade A for Env and for Gag, except for one patient who was
      infected with a clade A Env-clade G Gag recombinant virus. All patients infected
      in France were infected with clade B viruses. The CTL responses obtained from all
      the African and all the French individuals tested showed frequent cross-reactions
      with proteins of the heterologous clade. Epitopes conserved between the viruses
      of clades A and B appeared especially frequent in Gag p24, Gag p18, integrase,
      and the central region of Nef. Cross-reactivity also existed among Gag epitopes
      of clades A, B, and G, as shown by the results for the patient infected with the
      clade A Env-clade G Gag recombinant virus. These results show that CTLs raised
      against viral antigens from different clades are able to cross-react, emphasizing
      the possibility of obtaining cross-immunizations for this part of the immune
      response in vaccinated individuals.

PMID- 9557635
TI  - Elongation of the cytoplasmic tail interferes with the fusion activity of
      influenza virus hemagglutinin.
AB  - The hemagglutinin (HA) of fowl plague virus was lengthened and shortened by site
      specific mutagenesis at the cytoplasmic tail, and the effects of these
      modifications on HA functions were analyzed after expression from a simian virus
      40 vector. Elongation of the tail by the addition of one to six histidine (His)
      residues did not interfere with intracellular transport, glycosylation,
      proteolytic cleavage, acylation, cell surface expression, and hemadsorption.
      However, the ability to induce syncytia at a low pH decreased dramatically
      depending on the number of His residues added. Partial fusion (hemifusion),
      assayed by fluorescence transfer from octadecylrhodamine-labeled erythrocyte
      membranes, was also reduced, but even with the mutant carrying six His residues,
      significant transfer was observed. However, when the formation of fusion pores
      was examined with hydrophilic fluorescent calcein, transfer from erythrocytes to
      HA-expressing cells was not observed with the mutant carrying six histidine
      residues. The addition of different amino acids to the cytoplasmic tail of HA
      caused an inhibitory effect similar to that caused by the addition of His. On the
      other hand, a mutant lacking the cytoplasmic tail was still able to fuse at a
      reduced level. These results demonstrate that elongation of the cytoplasmic tail
      interferes with the formation and enlargement of fusion pores. Thus, the length
      of the cytoplasmic tail plays a critical role in the fusion process.

PMID- 9557636
TI  - Identification of regions of poliovirus 2BC protein that are involved in
      cytotoxicity.
AB  - The expression of poliovirus 2BC protein in yeast and mammalian cells leads to a
      number of metabolic and morphological alterations, such as growth inhibition,
      intracellular membrane proliferation, blockade of the exocytic pathway, and
      enhanced membrane permeability. Yeast cells that express poliovirus 2BC in an
      inducible manner were used to identify the regions of 2BC implicated in the
      modifications of these cellular functions. Several 2BC deletion mutants were
      generated to define the minimal portion of 2BC required to alter these
      activities. Additional deletion mutants that were obtained by random mutagenesis
      followed by selection in yeast cells provided new insights into the structure and
      mechanism of action of 2BC. The activity responsible for membrane proliferation
      is located in 2C, while the activities responsible for membrane permeabilization
      and inhibition of the exocytic pathway are located in 2B. Several regions of 2B
      and 2C required for the different functions of 2BC were identified. Thus, the
      integrity of the N termini of both 2B and 2C is necessary for 2BC-induced
      cytotoxicity. It is also possible to separate the different cellular alterations
      provoked by 2BC by the use of several 2BC variants. Deletion of amino acids 52 to
      65 in 2B generates a 2BC deletion variant, 2bC deltaAvrII, that still blocks
      yeast growth but is unable to enhance membrane permeability or to inhibit the
      exocytic pathway. On the other hand, 2Bcl28*.32b and 2Bcl28*.3c, which contain
      only 73 and 77 amino acids of 2B, interfere with yeast division and enhance
      membrane permeability but affect the exocytic pathway only weakly and do not
      induce membrane proliferation. Our findings indicate that Saccharomyces
      cerevisiae represents a useful model system to analyze the functions of
      poliovirus 2BC and show the feasibility of separating the activities assigned to
      this protein.

PMID- 9557637
TI  - Coding sequences enhance internal initiation of translation by hepatitis A virus
      RNA in vitro.
AB  - Hepatitis A virus (HAV), unlike other picornaviruses, has a slow-growth phenotype
      in permissive cell lines and in general does not induce host cell cytopathology.
      Although there are no published reports of productive infection of HeLa cells by
      HAV, HAV RNA appears to be readily translated in HeLa cells when transcribed by
      T7 RNA polymerase provided by a recombinant vaccinia virus. The 5' noncoding
      region of HAV was fused to poliovirus (PV) coding sequences to determine the
      effect on translation efficiency in HeLa cell extracts in vitro. Conditions were
      optimized for utilization of the HAV internal ribosome entry segment (IRES).
      Transcripts from chimeric constructs fused precisely at the initiation codon were
      translated very poorly. However, chimeric RNAs which included 114 or more
      nucleotides from the HAV capsid coding sequences downstream of the initiation
      codon were translated much more efficiently than those lacking these sequences,
      making HAV-directed translation efficiency similar to that directed by the PV
      IRES. Sixty-six nucleotides were insufficient to confer increased translation
      efficiency. The most 5'-terminal HAV 138 nucleotides, previously determined to be
      upstream of the IRES, had an inhibitory effect on translation efficiency.
      Constructs lacking these terminal sequences, or those in which the PV 5'-terminal
      sequences replaced those from HAV, translated three- to fourfold better than
      those with the intact HAV 5'-terminal end.

PMID- 9557638
TI  - Interaction of poliovirus with its purified receptor and conformational
      alteration in the virion.
AB  - Polypeptides of amino acids 1 to 241 (PVR241) and 1 to 330 (PVR330) of the human
      poliovirus receptor (hPVR) were produced in a baculovirus expression system.
      PVR241 contained extracellular domains 1 and 2 of hPVR, and PVR330 contained
      extracellular domains 1, 2, and 3. These peptides were purified by immunoaffinity
      column chromatography with an anti-hPVR monoclonal antibody (MAb). After the
      purification, PVR241 and PVR330 appeared to retain their native conformation as
      judged by reactivity with an anti-PVR MAb that recognized domain 1 of hPVR in a
      conformation-dependent manner. The virulent Mahoney strain of poliovirus type 1
      was mixed with the purified PVRs in various concentrations. An average of at
      least 43 PVR330 molecules were able to bind to one virion particle under the
      conditions used. The equilibrium dissociation constant between the PVR330
      molecule and the PVR binding site (canyon) on the virion was determined to be
      4.50 +/- (0.86) x 10(-8) M at 4 degrees C. Higher rates of conformational change
      of the virus (160S) to 135S and 80S particles were observed as the concentration
      of PVR330 was increased. In this in vitro system, the ratio of the amount of the
      135S particle to that of the 80S particle seemed to be always constant. After the
      disappearance of the 160S particle, the amount of the 80S particle was not
      increased by further incubation at 37 degrees C. These results suggested that the
      80S particle was not derived from the 135S particle under the conditions used in
      this study.

PMID- 9557639
TI  - Foot-and-mouth disease virus virulent for cattle utilizes the integrin
      alpha(v)beta3 as its receptor.
AB  - Adsorption and plaque formation of foot-and-mouth disease virus (FMDV) serotype
      A12 are inhibited by antibodies to the integrin alpha(v)beta3 (A. Berinstein et
      al., J. Virol. 69:2664-2666, 1995). A human cell line, K562, which does not
      normally express alpha(v)beta3 cannot replicate this serotype unless cells are
      transfected with cDNAs encoding this integrin (K562-alpha(v)beta3 cells). In
      contrast, we found that a tissue culture-propagated FMDV, type O1BFS, was able to
      replicate in nontransfected K562 cells, and replication was not inhibited by
      antibodies to the endogenously expressed integrin alpha5beta1. A recent report
      indicating that cell surface heparan sulfate (HS) was required for efficient
      infection of type O1 (T. Jackson et al., J. Virol. 70:5282-5287, 1996) led us to
      examine the role of HS and alpha(v)beta3 in FMDV infection. We transfected normal
      CHO cells, which express HS but not alpha(v)beta3, and two HS-deficient CHO cell
      lines with cDNAs encoding human alpha(v)beta3, producing a panel of cells that
      expressed one or both receptors. In these cells, type A12 replication was
      dependent on expression of alpha(v)beta3, whereas type O1BFS replicated to high
      titer in normal CHO cells but could not replicate in HS-deficient cells even when
      they expressed alpha(v)beta3. We have also analyzed two genetically engineered
      variants of type O1Campos, vCRM4, which has greatly reduced virulence in cattle
      and can bind to heparin-Sepharose columns, and vCRM8, which is highly virulent in
      cattle and cannot bind to heparin-Sepharose. vCRM4 replicated in wild-type K562
      cells and normal, nontransfected CHO (HS+ alpha(v)beta3-) cells, whereas vCRM8
      replicated only in K562 and CHO cells transfected with alpha(v)beta3 cDNAs. A
      similar result was also obtained in assays using a vCRM4 virus with an engineered
      RGD-->KGE mutation. These results indicate that virulent FMDV utilizes the
      alpha(v)beta3 integrin as a primary receptor for infection and that adaptation of
      type O1 virus to cell culture results in the ability of the virus to utilize HS
      as a receptor and a concomitant loss of virulence.

PMID- 9557641
TI  - Origin and rapid evolution of a novel murine erythroleukemia virus of the spleen
      focus-forming virus family.
AB  - The Friend spleen focus-forming virus (SFFV) env gene encodes a glycoprotein with
      apparent Mr of 55,000 that binds to erythropoietin receptors (EpoR) to stimulate
      erythroblastosis. A retroviral vector that does not encode any Env glycoprotein
      was packaged into retroviral particles and was coinjected into mice in the
      presence of a nonpathogenic helper virus. Although most mice remained healthy,
      one mouse developed splenomegaly and polycythemia at 67 days; the virus from this
      mouse reproducibly caused the same symptoms in secondary recipients by 2 to 3
      weeks postinfection. This disease, which was characterized by extramedullary
      erythropoietin-independent erythropoiesis in the spleens and livers, was also
      reproduced in long-term bone marrow cultures. Viruses from the diseased primary
      mouse and from secondary recipients converted an erythropoietin-dependent cell
      line (BaF3/EpoR) into factor-independent derivatives but had no effect on the
      interleukin-3-dependent parental BaF3 cells. Most of these factor-independent
      cell clones contained a major Env-related glycoprotein with an Mr of 60,000.
      During further in vivo passaging, a virus that encodes an Mr-55,000 glycoprotein
      became predominant. Sequence analysis indicated that the ultimate virus is a new
      SFFV that encodes a glycoprotein of 410 amino acids with the hallmark features of
      classical gp55s. Our results suggest that SFFV-related viruses can form in mice
      by recombination of retroviruses with genomic and helper virus sequences and that
      these novel viruses then evolve to become increasingly pathogenic.

PMID- 9557640
TI  - Monoclonal antibodies to distinct sites on herpes simplex virus (HSV)
      glycoprotein D block HSV binding to HVEM.
AB  - HVEM (for herpesvirus entry mediator) is a member of the tumor necrosis factor
      receptor superfamily and mediates entry of many strains of herpes simplex virus
      (HSV) into normally nonpermissive Chinese hamster ovary (CHO) cells. We used
      sucrose density centrifugation to demonstrate that purified HSV-1 KOS virions
      bind directly to a soluble, truncated form of HVEM (HVEMt) in the absence of any
      other cell-associated components. Therefore, HVEM mediates HSV entry by serving
      as a receptor for the virus. We previously showed that soluble, truncated forms
      of HSV glycoprotein D (gDt) bind to HVEMt in vitro. Here we show that antibodies
      specific for gD, but not the other entry glycoproteins gB, gC, or the gH/gL
      complex, completely block HSV binding to HVEM. Thus, virion gD is the principal
      mediator of HSV binding to HVEM. To map sites on virion gD which are necessary
      for its interaction with HVEM, we preincubated virions with gD-specific
      monoclonal antibodies (MAbs). MAbs that recognize antigenic sites Ib and VII of
      gD were the only MAbs which blocked the HSV-HVEM interaction. MAbs from these two
      groups failed to coprecipitate HVEMt in the presence of soluble gDt, whereas the
      other anti-gD MAbs coprecipitated HVEMt and gDt. Previous mapping data indicated
      that site VII includes amino acids 11 to 19 and site Ib includes 222 to 252. The
      current experiments indicate that these sites contain residues important for HSV
      binding to HVEM. Group Ib and VII MAbs also blocked HSV entry into HVEM
      expressing CHO cells. These results suggest that the mechanism of neutralization
      by these MAbs is via interference with the interaction between gD in the virus
      and HVEM on the cell. Group Ia and II MAbs failed to block HSV binding to HVEM
      yet still neutralized HVEM-mediated entry, suggesting that these MAbs block entry
      at a step other than HVEM binding.

PMID- 9557642
TI  - Nuclear matrix attachment regions of human papillomavirus type 16 point toward
      conservation of these genomic elements in all genital papillomaviruses.
AB  - The gene functions, transcriptional regulation, and genome replication of human
      papillomaviruses (HPVs) have been extensively studied. Thus far, however, there
      has been little research on the organization of HPV genomes in the nuclei of
      infected cells. As a first step to understand how chromatin and suprachromatin
      structures may modulate the life cycles of these viruses, we have identified and
      mapped interactions of HPV DNAs with the nuclear matrix. The endogenous genomes
      of HPV type 16 (HPV-16) which are present in SiHa, HPKI, and HPKII cells, adhere
      in vivo to the nuclear matrixes of these cell lines. A tight association with the
      nuclear matrix in vivo may be common to all genital HPV types, as the genomes of
      HPV-11, HPV-16, HPV-18, and HPV-33 showed high affinity in vitro to preparations
      of the nuclear matrix of C33A cells, as did the well-known nuclear matrix
      attachment region (MAR) of the cellular beta interferon gene. Affinity to the
      nuclear matrix is not evenly spread over the HPV-16 genome. Five genomic segments
      have strong MAR properties, while the other parts of the genome have low or no
      affinity. Some of the five MARs correlate with known cis-responsive elements: a
      strong MAR lies in the 5' segment of the long control region (LCR), and another
      one lies in the E6 gene, flanking the HPV enhancer, the replication origin, and
      the E6 promoter. The strongest MAR coincides with the E5 gene and the early-late
      intergenic region. Weak MAR activity is present in the E1 and E2 genes and in the
      3' part of L2. The in vitro map of MAR activity appears to reflect MAR properties
      in vivo, as we found for two selected fragments with and without MAR activity. As
      is typical for many MARs, the two segments with highest affinity, namely, the 5'
      LCR and the early-late intergenic region, have an extraordinarily high A-T
      content (up to 85%). It is likely that these MARs have specific functions in the
      viral life cycle, as MARs predicted by nucleotide sequence analysis, patterns of
      A-T content, transcription factor YY1 binding sites, and likely topoisomerase II
      cleavage sites are conserved in similar positions throughout all genital HPVs.

PMID- 9557643
TI  - Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4
      independent and gp120 dependent and requires cell surface heparans.
AB  - The binding of human immunodeficiency virus type 1 (HIV-1) (Hx10) virions to two
      different cell lines was analyzed by using a novel assay based on the detection,
      by anti-HLA-DR-specific antibodies, of HLA-DR+ virus binding to HLA-DR- cells.
      Virion attachment to the CD4+-T-cell line A3.01 was highly CD4 dependent in that
      it was potently inhibited by CD4 monoclonal antibodies (MAbs), and little virus
      binding to the CD4- sister A2.01 line was observed. By contrast, virion binding
      to HeLa cells expressing moderate or high levels of CD4 was equivalent to, or
      lower than, binding to wild-type CD4- HeLa cells. Moreover, several CD4 MAbs did
      not reduce, but enhanced, HIV-1 attachment to HeLa-CD4 cells. CD4 was required
      for infection of HeLa cells, however, demonstrating a postattachment role for
      this receptor. MAbs specific for the V2 and V3 loops and the CD4i epitope of
      gp120 strongly inhibited virion binding to HeLa-CD4 cells, whereas MAbs specific
      for the CD4bs and the 2G12 epitopes enhanced attachment. Despite this, all gp120-
      and gp41-specific MAbs tested neutralized infectivity on HeLa-CD4 cells. HIV-1
      attachment to HeLa cells was only partially inhibited by MAbs specific for
      adhesion molecules present on the virus or target cells but was completely
      blocked by polyanions such as heparin, dextran sulfate, and pentosan sulfate.
      Treatment of HeLa-CD4 cells with heparinases completely eliminated HIV attachment
      and infection, strongly implicating cell surface heparans in the attachment
      process. CD4 dependence for HIV-1 attachment to target cells is thus highly cell
      line specific and may be replaced by other ligand-receptor interactions.

PMID- 9557644
TI  - Cellular transcription factors enhance herpes simplex virus type 1 oriS-dependent
      DNA replication.
AB  - The herpes simplex virus type 1 (HSV-1) origin of DNA replication, oriS, contains
      three binding sites for the viral origin binding protein (OBP) flanked by
      transcriptional regulatory elements of the immediate-early genes encoding ICP4
      and ICP22/47. To assess the role of flanking sequences in oriS function, plasmids
      containing oriS and either wild-type or mutant flanking sequences were tested in
      transient DNA replication assays. Although the ICP4 and ICP22/47 regulatory
      regions were shown to enhance oriS function, most individual elements in these
      regions, including the VP16-responsive TAATGARAT elements, were found to be
      dispensable for oriS function. In contrast, two oriS core-adjacent regulatory
      (Oscar) elements, OscarL and OscarR, at the base of the oriS palindrome were
      shown to enhance oriS function significantly and additively. Specifically,
      mutational disruption of either element reduced oriS-dependent DNA replication by
      60 to 70%, and disruption of both elements reduced replication by 90%. The
      properties of protein-DNA complexes formed in gel mobility shift assays using
      uninfected and HSV-1-infected Vero cell nuclear extracts demonstrated that both
      OscarL and OscarR are binding sites for cellular proteins. Whereas OscarR does
      not correspond to the consensus binding site of any known transcription factor,
      OscarL contains a consensus binding site for the transcription factor Sp1. Gel
      mobility shift and supershift experiments using antibodies directed against
      members of the Sp1 family of transcription factors demonstrated the presence of
      Sp1 and Sp3, but not Sp2 or Sp4, in the protein-DNA complexes formed at OscarL.
      The abilities of OscarL and OscarR to bind their respective cellular proteins
      correlated directly with the efficiency of oriS-dependent DNA replication.
      Cooperative interactions between the Oscar-binding factors and proteins binding
      to adjacent OBP binding sites were not observed. Notably, Oscar element mutations
      that impaired oriS-dependent DNA replication had no detectable effect on either
      basal or induced levels of transcription from the ICP4 and ICP22/47 promoters, as
      determined by RNase protection assays. The Oscar elements thus appear to provide
      binding sites for cellular proteins that facilitate oriS-dependent DNA
      replication but have no effect on transcription of oriS-flanking genes.

PMID- 9557645
TI  - Grossly defective nef gene sequences in a human immunodeficiency virus type 1
      seropositive long-term nonprogressor.
AB  - We have been investigating a long-term nonprogressor who was found to be human
      immunodeficiency virus type 1 (HIV-1) seropositive in 1985 and has survived with
      stable CD4+ T-cell counts (>1,000 CD4 cells/microl) without any AIDS-related
      illness. We have previously reported that repeated attempts to measure HIV-1 RNA
      in the peripheral mononuclear cells obtained from this subject have invariably
      failed. In the present study, we have analyzed the molecular nature of the HIV-1
      quasispecies infecting this patient by PCR amplification of two proviral regions,
      the 5' long terminal repeat (5'LTR)/gag leader and the nef gene, directly from
      fresh uncultured peripheral mononuclear cells, followed by length polymorphism
      analysis (with 1994, 1995, and 1996 samples) and sequencing (with a 1996 sample).
      Only proviral forms with nef deletions were revealed by length polymorphism
      analysis in samples from all three time points. Sequence analysis of the nef gene
      from the 1996 sample confirmed the presence of similar proviral quasispecies
      characterized by the presence of several deletions located in the nef-alone and
      the nef/U3 overlapping regions. Length polymorphism analysis of the 5'LTR/gag
      leader region suggested the existence of two major quasispecies populations, one
      characterized by the presence of forms carrying deletions in the U3 region and
      the other showing a completely intact, full-length 5'LTR. Evidence of the role of
      nef gene defects in long-term survival of HIV-1-infected patients has been
      provided so far in two independent investigations involving patients infected
      with HIV through blood transfusion. Here we show the existence of a similar
      condition in a subject who acquired HIV-1 seropositivity through the sexual
      route.

PMID- 9557646
TI  - The roles of Pol and Env in the assembly pathway of human foamy virus.
AB  - Human foamy virus (HFV) is the prototype of the Spumavirus genus of retroviruses.
      These viruses have a genomic organization close to that of other complex
      retroviruses but have similarities to hepadnaviruses such as human hepatitis B
      virus (HBV). Both HFV and HBV express their Pol protein independently of their
      structural proteins. Retroviruses and hepadnaviruses differ in their requirements
      for particle assembly and genome packaging. Assembly of retroviral particles
      containing RNA genomes requires only the Gag structural protein. The Pol protein
      is not required for capsid assembly, and the Env surface glycoprotein is not
      required for release of virions from the cell. In contrast, assembly of
      extracellular HBV particles containing DNA requires core structural protein and
      polymerase (P protein) for assembly of nucleocapsids and requires surface
      glycoproteins for release from the cell. We investigated the requirements for
      synthesis of extracellular HFV particles by constructing mutants with either the
      pol or env gene deleted. We found that the Pol protein is dispensable for
      production of extracellular particles containing viral nucleic acid. In the
      absence of Env, intracellular particles are synthesized but few or no
      extracellular particles could be detected. Thus, foamy virus assembly is distinct
      from that of other reverse transcriptase-encoding mammalian viruses.

PMID- 9557647
TI  - Mutations in rotavirus nonstructural glycoprotein NSP4 are associated with
      altered virus virulence.
AB  - Rotaviruses are major pathogens causing life-threatening dehydrating
      gastroenteritis in children and animals. One of the nonstructural proteins, NSP4
      (encoded by gene 10), is a transmembrane, endoplasmic reticulum-specific
      glycoprotein. Recently, our laboratory has shown that NSP4 causes diarrhea in 6-
      to 10-day-old mice by functioning as an enterotoxin. To confirm the role of NSP4
      in rotavirus pathogenesis, we sequenced gene 10 from two pairs of virulent and
      attenuated porcine rotaviruses, the OSU and Gottfried strains. Comparisons of the
      NSP4 sequences from these two pairs of rotaviruses suggested that structural
      changes between amino acids (aa) 131 and 140 are important in pathogenesis. We
      next expressed the cloned gene 10 from the OSU virulent (OSU-v) and OSU
      attenuated (OSU-a) viruses by using the baculovirus expression system and
      compared the biological activities of the purified proteins. NSP4 from OSU-v
      virus increased intracellular calcium levels over 10-fold in intestinal cells
      when added exogenously and 6-fold in insect cells when expressed endogenously,
      whereas NSP4 from OSU-a virus had little effect. NSP4 from OSU-v caused diarrhea
      in 13 of 23 neonatal mice, while NSP4 from OSU-a caused disease in only 4 of 25
      mice (P < 0.01). These results suggest that avirulence is associated with
      mutations in NSP4. Results from site-directed mutational analyses showed that
      mutated OSU-v NSP4 with deletion or substitutions in the region of aa 131 to 140
      lost its ability to increase intracellular calcium levels and to induce diarrhea
      in neonatal mice, confirming the importance of amino acid changes from OSU-v NSP4
      to OSU-a NSP4 in the alteration of virus virulence.

PMID- 9557648
TI  - Structured-tree topology and adaptive evolution of the simian immunodeficiency
      virus SIVsm envelope during serial passage in rhesus macaques according to
      likelihood mapping and quartet puzzling.
AB  - Species-specific strains of simian immunodeficiency virus (SIV) are nonpathogenic
      in African primates. The SIV strain most closely related to human
      immunodeficiency virus type 2 (HIV-2) is SIVsm, the strain specific to the sooty
      mangabey (Cercocebus atys). Infection of Asian primates with SIV causes AIDS and
      allows the study of the adaptive evolution of a lentivirus to replicate
      efficiently in a new host, providing a useful animal model of HIV infection and
      AIDS in humans. Serial passage of SIVsm from sooty mangabeys in rhesus macaques
      drastically shortened the time of disease progression from 1.5 years to 1 month
      as the retrovirus adapted to these Asian hosts. In the present study we analyzed
      the quasispecies nature of the SIVsm envelope gene (env) during serial population
      passage in rhesus macaques. We asked ourselves if phylogenetic evidence could be
      provided for the structured topology of the SIVsm env tree and subsequently for
      the adaptive evolution of SIVsm env. Likelihood mapping showed that phylogenetic
      reconstruction of the passage was possible because a high percentage of the
      sequence data had a "tree-like" form. Subsequently, quartet puzzling was used and
      produced a phylogeny with a structure parallel to the known infection history.
      The adaptation of SIVsm to Asian rhesus macaques appears to be an ordered process
      in which the env evolves in a tree-like manner, particularly in its constant
      regions.

PMID- 9557649
TI  - Hepatitis delta antigen mediates the nuclear import of hepatitis delta virus RNA.
AB  - Hepatitis delta virus (HDV) RNA replicates in the nuclei of virus-infected cells.
      The mechanism of nuclear import of HDV RNA is so far unknown. Using a fluorescein
      labeled HDV RNA introduced into partially permeabilized HeLa cells, we found that
      HDV RNA accumulated only in the cytoplasm. However, in the presence of hepatitis
      delta antigen (HDAg), which is the only protein encoded by HDV RNA, the HDV RNA
      was translocated into the nucleus, suggesting that nuclear import of HDV RNA is
      mediated by HDAg. Deletion of the nuclear localization signal (NLS) or RNA
      binding motifs of HDAg resulted in the failure of nuclear import of HDV RNA,
      indicating that both the NLS and an RNA-binding motif of HDAg are required for
      the RNA-transporting activity of HDAg. Surprisingly, any one of the three
      previously identified RNA-binding motifs was sufficient to confer the RNA
      transporting activity. We have further shown that HDAg, via its NLS, interacts
      with karyopherin alpha2 in vitro, suggesting that nuclear import of the HDAg-HDV
      RNA complex is mediated by the karyopherin alpha2beta heterodimer. The nuclear
      import of HDV RNA may be the first biological function of HDAg in the HDV life
      cycle.

PMID- 9557650
TI  - Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis
      factor (TNF) receptor 1 and enhances TNF-induced apoptosis.
AB  - The hepatitis C virus (HCV) core protein is known to be a multifunctional
      protein, besides being a component of viral nucleocapsids. Previously, we have
      shown that the core protein binds to the cytoplasmic domain of lymphotoxin beta
      receptor, which is a member of tumor necrosis factor receptor (TNFR) family. In
      this study, we demonstrated that the core protein also binds to the cytoplasmic
      domain of TNFR 1. The interaction was demonstrated both by glutathione S
      transferase fusion protein pull-down assay in vitro and membrane flotation method
      in vivo. Both the in vivo and in vitro binding required amino acid residues 345
      to 407 of TNFR 1, which corresponds to the "death domain" of this receptor. We
      have further shown that stable expression of the core protein in a mouse cell
      line (BC10ME) or human cell lines (HepG2 and HeLa cells) sensitized them to TNF
      induced apoptosis, as determined by the TNF cytotoxicity or annexin V apoptosis
      assay. The presence of the core protein did not alter the level of TNFR 1 mRNA in
      the cells or expression of TNFR 1 on the cell surface, suggesting that the
      sensitization of cells to TNF by the viral core protein was not due to up
      regulation of TNFR 1. Furthermore, we observed that the core protein blocked the
      TNF-induced activation of RelA/NF-kappaB in murine BC10ME cells, thus at least
      partially accounting for the increased sensitivity of BC10ME cells to TNF.
      However, NF-kappaB activation was not blocked in core protein-expressing HeLa or
      HepG2 cells, implying another mechanism of TNF sensitization by core protein.
      These results together suggest that the core protein can promote cell death
      during HCV infection via TNF signaling pathways possibly as a result of its
      interaction with the cytoplasmic tail of TNFR 1. Therefore, TNF may play a role
      in HCV pathogenesis.

PMID- 9557651
TI  - Substitution of ras for the herpesvirus saimiri STP oncogene in lymphocyte
      transformation.
AB  - STP-C488 (STP of herpesvirus saimiri [HVS] group C strain 488 [C488]) is the only
      virus-encoded protein found to associate with cellular ras and activate ras
      signal transduction pathways. To investigate an important role for ras signal
      transduction in STP-dependent growth transformation, we constructed recombinant
      strains of HVS C488 in which the STP-C488 oncogene was replaced with cellular
      normal ras (c-ras) or viral oncogenic ras (v-ras). Recombinant HVS deltaSTP/v-ras
      immortalized primary common marmoset T lymphocytes to interleukin-2-independent
      growth as efficiently as wild-type HVS C488 (wt HVS), while recombinant HVS
      deltaSTP/c-ras did so with low efficiency. Whereas wt HVS immortalized CD4- CD8+
      single-positive T lymphocytes, HVS deltaSTP/c-ras- and HVS deltaSTP/v-ras
      immortalized cells were principally CD4+ CD8+ double-positive T lymphocytes. In
      addition, HVS deltaSTP/v-ras-immortalized T cells showed a high level of ras
      expression and exhibited an adherent macrophage-like morphology. These phenotypes
      were likely caused by the drastic activation of AP-1 transcriptional factor
      activity. Finally, HVS deltaSTP/v-ras and HVS deltaSTP/c-ras each induced
      lymphoma in one of two common marmosets, although onset of disease was more rapid
      with the v-ras virus. These results demonstrate that ras can substitute for the
      STP oncogene of HVS C488 to allow immortalized growth of primary lymphoid cells
      and that an activated form of ras does so more efficiently than the normal
      cellular form of ras.

PMID- 9557653
TI  - Collaboration of antibody and inflammation in clearance of rabies virus from the
      central nervous system.
AB  - To investigate the involvement of various cellular and humoral aspects of
      immunity in the clearance of rabies virus from the central nervous system, (CNS),
      we studied the development of clinical signs and virus clearance from the CNS in
      knockout mice lacking either B and T cells, CD8+ cytotoxic T cells, B cells,
      alpha/beta interferon (IFN-alpha/beta) receptors, IFN-gamma receptors, or
      complement components C3 and C4. Following intranasal infection with the
      attenuated rabies virus CVS-F3, normal adult mice of different genetic
      backgrounds developed a transient disease characterized by loss of body weight
      and appetite depression which peaked at 13 days postinfection (p.i.). While these
      animals had completely recovered by day 21 p.i., mice lacking either B and T
      cells or B cells alone developed a progressive disease and succumbed to
      infection. Mice lacking either CD8+ T cells, IFN receptors, or complement
      components C3 and C4 showed no significant differences in the development of
      clinical signs by comparison with intact counterparts having the same genetic
      background. However, while infectious virus and viral RNA could be detected in
      normal control mice only until day 8 p.i., in all of the gene knockout mice
      studied except those lacking C3 and C4, virus infection persisted through day 21
      p.i. Analysis of rabies virus-specific antibody production together with
      histological assessment of brain inflammation in infected animals revealed that
      clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory
      response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10
      p.i.) production of significant levels of virus-neutralizing antibody (VNA).
      These studies confirm that rabies VNA is an absolute requirement for clearance of
      an established rabies virus infection. However, for the latter to occur in a
      timely fashion, collaboration between VNA and inflammatory mechanisms is
      necessary.

PMID- 9557652
TI  - Absence of macrophage inflammatory protein-1alpha prevents the development of
      blinding herpes stromal keratitis.
AB  - Prior studies in our laboratory have suggested that the CC chemokine macrophage
      inflammatory protein-1alpha (MIP-1alpha) may be an important mediator in the
      blinding ocular inflammation which develops following herpes simplex virus type 1
      (HSV-1) infection of the murine cornea. To directly test this hypothesis, MIP
      1alpha-deficient (-/-) mice and their wild-type (+/+) counterparts were infected
      topically on the scarified cornea with 2.5 x 10(5) PFU of HSV-1 strain RE and
      subsequently graded for corneal opacity. Four weeks postinfection (p.i.), the
      mean corneal opacity score of -/- mice was 1.1 +/- 0.3 while that of the +/+ mice
      was 3.7 +/- 0.5. No detectable infiltrating CD4+ T cells were seen histologically
      at 14 or 21 days p.i. in -/- animals, whereas the mean CD4+ T-cell count per
      field (36 fields counted) in +/+ hosts was 26 +/- 2 (P < 0.001). In addition,
      neutrophil counts in the -/- mouse corneas were reduced by >80% in comparison to
      the wild-type controls. At 2 weeks p.i., no interleukin-2 or gamma interferon
      could be detected in six of seven -/- mice, whereas both T-cell cytokines were
      readily demonstrable in +/+ mouse corneas. Also, MIP-2 and monocyte
      chemoattractant protein-1 protein levels were significantly lower in MIP-1alpha 
      /- mouse corneas than in +/+ host corneas, suggesting that MIP-1alpha directly,
      or more likely indirectly, influences the expression of other chemokines.
      Interestingly, despite the paucity of infiltrating cells, HSV-1 clearance from
      the eyes of -/- mice was not significantly different from that observed in +/+
      hosts. We conclude that MIP-1alpha is not needed to control virus growth in the
      cornea but is essential for the development of severe stromal keratitis.

PMID- 9557654
TI  - Scaffold attachment region-mediated enhancement of retroviral vector expression
      in primary T cells.
AB  - We have studied retroviral transgene expression in primary human lymphocytes. Our
      data demonstrate that transgene expression is high in activated primary CD4+ T
      cells but significantly decreased in mitotically quiescent cells. Incorporation
      of a DNA fragment from the scaffold attachment region (SAR) of the human beta
      interferon gene into the vector improved transgene expression, particularly in
      quiescent cells. The SAR element functioned in an orientation-dependent manner
      and enhanced expression of Moloney murine leukemia virus- and murine embryonic
      stem cell-based vectors. Clonal analysis of transduced T cells showed that the
      SAR sequence did not confer position-independent expression on a transgene but
      rather prevented the decrease of expression when cells became quiescent. The SAR
      sequence also enhanced transgene expression in T cells generated from
      retrovirally transduced CD34-enriched hematopoietic progenitor-stem cells in a
      SCID-hu thymus-liver mouse model. We have used the SAR-containing retroviral
      vector to express the RevM10 gene, a trans-dominant mutant of the human
      immunodeficiency virus type 1 (HIV-1) Rev gene. Compared to a standard retroviral
      vector, the SAR-containing vector was up to 2 orders of magnitude more efficient
      in inhibiting replication of the HIV-1 virus in infected CD4+ peripheral blood
      lymphocyte populations in vitro. This is the first demonstration that SAR
      elements can be used to improve retroviral vector expression in human primary T
      cells.

PMID- 9557655
TI  - Cell cycle dysregulation by human cytomegalovirus: influence of the cell cycle
      phase at the time of infection and effects on cyclin transcription.
AB  - Human cytomegalovirus (HCMV) infection inhibits cell cycle progression and alters
      the expression of cyclins E, A, and B (F. M. Jault, J.-M. Jault, F. Ruchti, E. A.
      Fortunato, C. Clark, J. Corbeil, D. D. Richman, and D. H. Spector, J. Virol.
      69:6697-6704, 1995). In this study, we examined cell cycle progression, cyclin
      gene expression, and early viral events when the infection was initiated at
      different points in the cell cycle (G0, G1, and S). In all cases, infection led
      to cell cycle arrest. Cells infected in G0 or G1 phase also showed a complete or
      partial absence, respectively, of cellular DNA synthesis at a time when DNA
      synthesis occurred in the corresponding mock-infected cells. In contrast, when
      cells were infected near or during S phase, many cells were able to pass through
      S phase and undergo mitosis prior to cell cycle arrest. S-phase infection also
      produced a delay in the appearance of the viral cytopathic effect and in the
      synthesis of immediate-early and early proteins. Labeling of cells with
      bromodeoxyuridine immediately prior to HCMV infection in S phase revealed that
      viral protein expression occurred primarily in cells which were not engaged in
      DNA synthesis at the time of infection. The viral-mediated induction of cyclin E,
      maintenance of cyclin-B protein levels, and inhibitory effects on the
      accumulation of cyclin A were not significantly affected when infection occurred
      during different phases of the cell cycle (G0, G1, and S). However, there was a
      delay in the observed inhibition of cyclin A in cells infected during S phase.
      This finding was in accord with the pattern of cell cycle progression and delay
      in viral gene expression associated with S-phase infection. Analysis of the mRNA
      revealed that the effects of the virus on cyclin E and cyclin A, but not on
      cyclin B, were primarily at the transcriptional level.

PMID- 9557656
TI  - An array of novel murine spleen focus-forming viruses that activate the
      erythropoietin receptor.
AB  - The Friend spleen focus-forming virus (SFFV) env gene encodes a 409-amino-acid
      glycoprotein with an apparent Mr of 55,000 (gp55) that binds to erythropoietin
      receptors (EpoR) to stimulate erythroblastosis. We reported previously the in
      vivo selection during serial passages in mice of several evolutionary
      intermediates that culminated in the formation of a novel SFFV (M. E. Hoatlin, E.
      Gomez-Lucia, F. Lilly, J. H. Beckstead, and D. Kabat, J. Virol. 72:3602-3609,
      1998). A mouse injected with a retroviral vector in the presence of a
      nonpathogenic helper virus developed long-latency erythroblastosis, and
      subsequent viral passages resulted in more pathogenic isolates. The viruses taken
      from these mice converted an erythropoietin-dependent cell line (BaF3/EpoR) into
      factor-independent derivatives. Western blot analysis of cell extracts with an
      antiserum that broadly reacts with murine retroviral envelope glycoproteins
      suggested that the spleen from the initial mouse with mild erythoblastosis
      contained an array of viral components that were capable of activating EpoR. DNA
      sequence analysis of the viral genomes cloned from different factor-independent
      cell clones revealed env genes with open reading frames encoding 644, 449, and
      187 amino acids. All three env genes contained 3' regions identical to that of
      SFFV, including a 6-bp duplication and a single-base insertion that have been
      shown previously to be critical for pathogenesis. However, the three env gene
      sequences did not contain any polytropic sequences and were divergent in their 5'
      regions, suggesting that they had originated by recombination and partial
      deletions of endogenously inherited MuLV env sequences. These results suggest
      that the requirements for EpoR activation by SFFV-related viruses are dependent
      on sequences at the 3' end of the env gene and not on the polytropic regions or
      on the 585-base deletions that are common among the classical strains of SFFV.
      Moreover, sequence analysis of the different recombinants and deletion mutants
      revealed that short direct and indirect repeat sequences frequently flanked the
      deletions that had occurred, suggesting a reverse transcriptase template jumping
      mechanism for this rapid retroviral diversification.

PMID- 9557657
TI  - The Cys-rich region of hepatitis A virus cellular receptor 1 is required for
      binding of hepatitis A virus and protective monoclonal antibody 190/4.
AB  - The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA codes for a class I
      integral membrane glycoprotein, termed havcr-1, of unknown natural function which
      serves as an African green monkey kidney (AGMK) cell receptor for HAV. The
      extracellular domain of havcr-1 has an N-terminal Cys-rich region that displays
      homology with sequences of members of the immunoglobulin superfamily, followed by
      a Thr/Ser/Pro (TSP)-rich region characteristic of mucin-like O-glycosylated
      proteins. The havcr-1 glycoprotein contains four putative N-glycosylation sites,
      two in the Cys-rich region and two in the TSP-rich region. To characterize havcr
      1 and define region(s) involved in HAV receptor function, we expressed the TSP
      rich region in Escherichia coli fused to glutathione S-transferase and generated
      antibodies (Ab) in rabbits (anti-GST2 Ab). Western blot analysis with anti-GST2
      Ab detected 62- and 65-kDa bands in AGMK cells and 59-, 62-, and 65-kDa bands in
      dog cells transfected with the HAVcr-1 cDNA (cr5 cells) but not in dog cells
      transfected with the vector alone (DR2 cells). Treatment of AGMK and cr5 cell
      extracts with peptide-N-glycosidase F resulted in the collapse of the havcr-1
      specific bands into a single band of 56 kDa, which indicated that different N
      glycosylated forms of havcr-1 were expressed in these cells. Treatment of AGMK
      and cr5 cells with tunicamycin reduced binding of protective monoclonal Ab (MAb)
      190/4, which suggested that N-glycans are required for binding of MAb 190/4 to
      havcr-1. To test this hypothesis, havcr-1 mutants lacking the N-glycosylation
      motif at the first site (mut1), second site (mut2), and both (mut3) sites were
      constructed and transfected into dog cells. Binding of MAb 190/4 and HAV to mut1
      and mut3 cells was highly reduced, while binding to mut2 cells was not affected
      and binding to dog cells expressing an havcr-1 construct containing a deletion of
      the Cys-rich region (d1- cells) was undetectable. HAV-infected cr5 and mut2 cells
      but not mut1, mut3, d1-, and DR2 cells developed the characteristic cytoplasmic
      granular fluorescence of HAV-infected cells. These results indicate that the Cys
      rich region of havcr-1 and its first N-glycosylation site are required for
      binding of protective MAb 190/4 and HAV receptor function.

PMID- 9557658
TI  - Transgenic mice secreting coronavirus neutralizing antibodies into the milk.
AB  - Ten lines of transgenic mice secreting transmissible gastroenteritis coronavirus
      (TGEV) neutralizing recombinant monoclonal antibodies (rMAbs) into the milk were
      generated. The rMAb light- and heavy-chain genes were assembled by fusing the
      genes encoding the variable modules of the murine MAb 6A.C3, which binds an
      interspecies conserved coronavirus epitope essential for virus infectivity, and a
      constant module from a porcine myeloma with the immunoglobulin A (IgA) isotype.
      The chimeric antibody led to dimer formation in the presence of J chain. The
      neutralization specific activity of the recombinant antibody produced in
      transiently or stably transformed cells was 50-fold higher than that of a
      monomeric rMAb with the IgG1 isotype and an identical binding site. This rMAb had
      titers of up to 10(4) by radioimmunoassay (RIA) and neutralized virus infectivity
      up to 10(4)-fold. Of 23 transgenic mice, 17 integrated both light and heavy
      chains, and at least 10 of them transmitted both genes to the progeny, leading to
      100% of animals secreting functional TGEV neutralizing antibody during lactation.
      Selected mice produced milk with TGEV-specific antibody titers higher than 10(6)
      as determined by RIA, neutralized virus infectivity by 10(6)-fold, and produced
      up to 6 mg of antibody per ml. Antibody expression levels were transgene copy
      number independent and integration site dependent. Comicroinjection of the
      genomic beta-lactoglobulin gene with rMAb light- and heavy-chain genes led to the
      generation of transgenic mice carrying the three transgenes. The highest antibody
      titers were produced by transgenic mice that had integrated the antibody and beta
      lactoglobulin genes, although the number of transgenic animals generated does not
      allow a definitive conclusion on the enhancing effect of beta-lactoglobulin
      cointegration. This approach may lead to the generation of transgenic animals
      providing lactogenic immunity to their progeny against enteric pathogens.

PMID- 9557659
TI  - Relative replicative fitness of zidovudine-resistant human immunodeficiency virus
      type 1 isolates in vitro.
AB  - Replication of mixtures of two or more human immunodeficiency virus type 1 (HIV
      1) variants would be expected to result in the eventual selection of the fittest
      virus due to Darwinian competition among the variants. The relative proportions
      of known HIV-1 variants (which may differ only by a single nucleotide from a
      standard "wild-type" virus, HIV-1HXB2) in mixed viral cultures were quantified by
      analysis of automated sequence signals of reverse transcriptase PCR products.
      With this method, the relative levels of replicative fitness of several
      zidovudine (3'-azidothymidine)-resistant HIV-1HXB2 variants were estimated under
      controlled in vitro conditions by measuring the rate of change in the proportions
      of viral variants as they replicated in cell cultures both in the presence and in
      the absence of drug selection pressure. These variants were engineered to contain
      commonly observed zidovudine resistance mutations in the HIV-1 reverse
      transcriptase (M41L, K70R, T215Y, and M41L+T215Y). In the absence of zidovudine,
      all variants tested displayed reduced replicative fitness compared to wild-type
      HIV-1HXB2. The order of relative fitness was wild type > K70R >> T215Y =
      M41L+T215Y > M41L. Mixed cultures in the presence of zidovudine showed a dose
      dependent selection pressure against the wild-type virus which varied according
      to the resistance profile of each virus. The information gathered from this
      approach provides insight into competition among multiple HIV-1 variants, which
      likely occurs in vivo with drug selection pressure, and may be applicable in more
      complex mathematical models for predicting the emergence of HIV-1 variants after
      the initiation of antiretroviral therapy.

PMID- 9557661
TI  - Effect of cleavage mutants on syncytium formation directed by the wild-type
      fusion protein of Newcastle disease virus.
AB  - The effects of Newcastle disease virus (NDV) fusion (F) glycoprotein cleavage
      mutants on the cleavage and syncytium-forming activity of the wild-type F protein
      were examined. F protein cleavage mutants were made by altering amino acids in
      the furin recognition region (amino acids 112 to 116) in the F protein of a
      virulent strain of NDV. Four mutants were made: Q114P replaced the glutamine
      residue with proline; K115G replaced lysine with glycine; double mutant K115G,
      R113G replaced both a lysine and an arginine with glycine residues; and a triple
      mutant, R112G, K115G, F117L, replaced three amino acids to mimic the sequence
      found in avirulent strains of NDV. All mutants except Q114P were cleavage
      negative and fusion negative. However, addition of exogenous trypsin cleaved all
      mutant F proteins and activated fusion. As expected for an oligomeric protein,
      the fusion-negative mutants had a dominant negative phenotype: cotransfection of
      wild-type and mutant F protein cDNAs resulted in an inhibition of syncytium
      formation. The presence of the mutant F protein did not inhibit cleavage of the
      wild-type protein. Furthermore, evidence is presented that suggests that the
      mutant protein and the wild-type protein formed heterooligomers. By measuring the
      syncytium-forming activity of the wild-type protein at various ratios of
      expression of mutant and wild-type protein, results were obtained that are most
      consistent with the notion that the size of the functionally active NDV F protein
      in these assays is a single oligomer, likely a trimer. That a larger oligomer,
      containing a mix of both wild-type and mutant F proteins, has partial activity
      cannot, however, be ruled out.

PMID- 9557662
TI  - Phosphorylation of the core protein of hepatitis B virus by a 46-kilodalton
      serine kinase.
AB  - Core protein is the major component of the core particle (nucleocapsid) of human
      hepatitis B virus. Core particles and core proteins are involved in a number of
      important functions in the replication cycle of the virus, including RNA
      packaging, DNA synthesis, and recognition of viral envelope proteins. Core
      protein is a phosphoprotein with most, if not all, of the phosphorylation on C
      terminal serine residues. In this study, we identified a serine kinase activity
      from the ribosome-associated protein fraction of cytoplasm that could
      specifically bind and phosphorylate the C-terminal portion of recombinant core
      protein. This kinase is referred to as core-associated kinase (CAK). CAK could be
      inhibited by the kinase inhibitors heparin and manganese ions but not by
      spermidine, DRB, H89, or H7, indicating that CAK is distinct from protein kinase
      A and protein kinase C. CAK could be partially purified by heparin-Sepharose CL
      6B and phosphocellulose P11 columns. By using a far-Western assay, three specific
      proteins, of 46, 35, and 13 kDa, were shown to interact with the C-terminal part
      of the core protein. These three proteins were present only in the eluted
      fractions that contains the CAK activity. An in-gel kinase assay showed that a 46
      kDa kinase in the same fraction could bind and phosphorylate the C-terminal part
      of the recombinant core protein. These results indicate that this 46-kDa kinase
      is most probably CAK. A similar 46-kDa kinase, which exhibits the same profile of
      sensitivity to kinase inhibitors as that of CAK, is present in both purified
      intracellular core particles and extracellular 42-nm virions, suggesting that CAK
      is a candidate for the core particle-associated kinase.

PMID- 9557660
TI  - The herpes simplex virus type 1 U(L)17 gene encodes virion tegument proteins that
      are required for cleavage and packaging of viral DNA.
AB  - Previous studies have suggested that the U(L)17 gene of herpes simplex virus type
      1 (HSV-1) is essential for virus replication. In this study, viral mutants
      incorporating either a lacZ expression cassette in place of 1,490 bp of the 2,109
      bp U(L)17 open reading frame [HSV-1(deltaU(L)17)] or a DNA oligomer containing an
      in-frame stop codon inserted 778 bp from the 5' end of the U(L)17 open reading
      frame [HSV-1(U(L)17-stop)] were plaque purified on engineered cell lines
      containing the U(L)17 gene. A virus derived from HSV-1(U(L)17-stop) but
      containing a restored U(L)17 gene was also constructed and was designated HSV
      1(U(L)17-restored). The latter virus formed plaques and cleaved genomic viral DNA
      in a manner indistinguishable from wild-type virus. Neither HSV-1(deltaU(L)17)
      nor HSV-1(U(L)17-stop) formed plaques or produced infectious progeny when
      propagated on noncomplementing Vero cells. Furthermore, genomic end-specific
      restriction fragments were not detected in DNA purified from noncomplementing
      cells infected with HSV-1(deltaU(L)17) or HSV-1(U(L)17-stop), whereas end
      specific fragments were readily detected when the viruses were propagated on
      complementing cells. Electron micrographs of thin sections of cells infected with
      HSV-1(deltaU(L)17) or HSV-1(U(L)17-stop) illustrated that empty capsids
      accumulated in the nuclei of Vero cells, whereas DNA-containing capsids
      accumulated in the nuclei of complementing cells and enveloped virions were found
      in the cytoplasm and extracellular space. Additionally, protein profiles of
      capsids purified from cells infected with HSV-1(deltaU(L)17) compared to wild
      type virus show no detectable differences. These data indicate that the U(L)17
      gene is essential for virus replication and is required for cleavage and
      packaging of viral DNA. To characterize the U(L)17 gene product, an anti-U(L)17
      rabbit polyclonal antiserum was produced. The antiserum reacted strongly with a
      major protein of apparent Mr 77,000 and weakly with a protein of apparent Mr
      72,000 in wild-type infected cell lysates and in virions. Bands of similar sizes
      were also detected in electrophoretically separated tegument fractions of virions
      and light particles and yielded tryptic peptides of masses characteristic of the
      predicted U(L)17 protein. We therefore conclude that the U(L)17 gene products are
      associated with the virion tegument and note that they are the first tegument
      associated proteins shown to be required for cleavage and packaging of viral DNA.

PMID- 9557663
TI  - The class II membrane glycoprotein G of bovine respiratory syncytial virus,
      expressed from a synthetic open reading frame, is incorporated into virions of
      recombinant bovine herpesvirus 1.
AB  - The bovine herpesvirus 1 (BHV-1) recombinants BHV-1/eG(ori) and BHV-1/eG(syn)
      were isolated after insertion of expression cassettes which contained either a
      genomic RNA-derived cDNA fragment (BHV-1/eG(ori)) or a modified, chemically
      synthesized open reading frame (ORF) (BHV-1/eG(syn)), which both encode the
      attachment glycoprotein G of bovine respiratory syncytial virus (BRSV), a class
      II membrane glycoprotein. Northern blot analyses and nuclear runoff transcription
      experiments indicated that transcripts encompassing the authentic BRSV G ORF were
      unstable in the nucleus of BHV-1/eG(ori)-infected cells. In contrast, high levels
      of BRSV G RNA were detected in BHV-1/eG(syn)-infected cells. Immunoblots showed
      that the BHV-1/eG(syn)-expressed BRSV G glycoprotein contains N- and O-linked
      carbohydrates and that it is incorporated into the membrane of infected cells and
      into the envelope of BHV-1/eG(syn) virions. The latter was also demonstrated by
      neutralization of BHV-1/eG(syn) infectivity by monoclonal antibodies or
      polyclonal anti-BRSV G antisera and complement. Our results show that expression
      of the BRSV G glycoprotein by BHV-1 was dependent on the modification of the BRSV
      G ORF and indicate that incorporation of class II membrane glycoproteins into BHV
      1 virions does not necessarily require BHV-1-specific signals. This raises the
      possibility of targeting heterologous polypeptides to the viral envelope, which
      might enable the construction of BHV-1 recombinants with new biological
      properties and the development of improved BHV-1-based live and inactivated
      vector vaccines.

PMID- 9557664
TI  - Dendritic cells efficiently induce protective antiviral immunity.
AB  - Cytotoxic T lymphocytes (CTL) are essential for effective immunity to various
      viral infections. Because of the high speed of viral replication, control of
      viral infections imposes demanding functional and qualitative requirements on
      protective T-cell responses. Dendritic cells (DC) have been shown to efficiently
      acquire, transport, and present antigens to naive CTL in vitro and in vivo. In
      this study, we assessed the potential of DC, either pulsed with the lymphocytic
      choriomeningitis virus (LCMV)-specific peptide GP33-41 or constitutively
      expressing the respective epitope, to induce LCMV-specific antiviral immunity in
      vivo. Comparing different application routes, we found that only 100 to 1,000 DC
      had to reach the spleen to achieve protective levels of CTL activation. The DC
      induced antiviral immune response developed rapidly and was long lasting. Already
      at day 2 after a single intravenous immunization with high doses of DC (1 x 10(5)
      to 5 x 10(5)), mice were fully protected against LCMV challenge infection, and
      direct ex vivo cytotoxicity was detectable at day 4 after DC immunization. At day
      60, mice were still protected against LCMV challenge infection. Importantly,
      priming with DC also conferred protection against infections in which the homing
      of CTL into peripheral organs is essential: DC-immunized mice rapidly cleared an
      infection with recombinant vaccinia virus-LCMV from the ovaries and eliminated
      LCMV from the brain, thereby avoiding lethal choriomeningitis. A comparison of DC
      constitutively expressing the GP33-41 epitope with exogenously peptide-pulsed DC
      showed that in vivo CTL priming with peptide-loaded DC is not limited by turnover
      of peptide-major histocompatibility complex class I complexes. We conclude that
      the priming of antiviral CTL responses with DC is highly efficient, rapid, and
      long lasting. Therefore, the use of DC should be considered as an efficient means
      of immunization for antiviral vaccination strategies.

PMID- 9557665
TI  - Two RING finger proteins, the oncoprotein PML and the arenavirus Z protein,
      colocalize with the nuclear fraction of the ribosomal P proteins.
AB  - The promyelocytic leukemia (PML) protein forms nuclear bodies which are relocated
      to the cytoplasm by the RNA virus lymphocytic choriomeningitis virus (LCMV). The
      viral Z protein directly binds to PML and can relocate the nuclear bodies. Others
      have observed that LCMV virions may contain ribosomes; hence, we investigated the
      effects of infection on the distribution of ribosomal P proteins (P0, P1, and P2)
      with PML as a reference point. We demonstrate an association of PML bodies with P
      proteins by indirect immunofluorescence and coimmunoprecipitation experiments,
      providing the first evidence of nucleic acid-binding proteins associated with PML
      bodies. We show that unlike PML, the P proteins are not redistributed upon
      infection. Immunofluorescence and coimmunoprecipitation studies indicate that the
      viral Z protein binds the nuclear, but not the cytoplasmic, fraction of P0. The
      nuclear fraction of P0 has been associated with translationally coupled DNA
      excision repair and with nonspecific endonuclease activity; thus, P0 may be
      involved in nucleic acid processing activities necessary for LCMV replication.
      During the infection process, PML, P1, and P2 are downregulated but P0 remains
      unchanged. Further, P0 is present in virions while PML is not, indicating some
      selectivity in the assembly of LCMV.

PMID- 9557666
TI  - Hepatitis C virus structural proteins assemble into viruslike particles in insect
      cells.
AB  - Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. The
      study of HCV has been hampered by the low level of viral particles in infected
      individuals, the inability to propagate efficiently the virus in cultured cells,
      and the lack of a convenient animal model. Due to these obstacles, neither the
      structure of the virus nor the prerequisites for its assembly have been clearly
      defined. In this report, we describe a model for the production and purification
      of HCV-like particles in insect cells using a recombinant baculovirus containing
      the cDNA of the HCV structural proteins. In insect cells, expressed HCV
      structural proteins assembled into enveloped viruslike particles (40 to 60 nm in
      diameter) in large cytoplasmic cisternae, presumably derived from the endoplasmic
      reticulum. Biophysical characterization of viruslike particles by CsCl and
      sucrose gradient centrifugation revealed biophysical properties similar to those
      of putative virions isolated from infected humans. The results suggested that HCV
      core and envelope proteins without p7 were sufficient for viral particle
      formation. Analysis of particle-associated nucleic acids demonstrated that HCV
      RNAs were selectively incorporated into the particles over non-HCV transcripts.
      The synthesis of HCV-like particles in insect cells may provide an important tool
      to determine the structural requirements for HCV particle assembly as well as to
      study viral genome encapsidation and virus-host interactions. The described
      system may also represent a potential approach toward vaccine development.

PMID- 9557667
TI  - Temporal mapping of transcripts in herpesvirus 6 variants.
AB  - To define the molecular features characteristic of the early stages of infection
      of lymphocytes with human herpesvirus 6 (HHV-6) variant A or B, we studied the
      temporal regulation of expression of selected sets of viral genes. Thus, U42,
      U94, U89-U90, U73, and U39 are alpha genes since their transcripts (i) were made
      in the presence of inhibitors of protein synthesis and (ii) were detected 3 h
      after infection of untreated cells. U41, U53, U31, and U19 are beta genes since
      their expression is inhibited by cycloheximide but not by phosphonoacetate, an
      inhibitor of DNA synthesis. U100 is a gamma gene since its spliced transcript
      encoding the structural glycoprotein gp82/105 was first detected 16 h after
      infection of untreated cells but could not be detected in cells treated with
      phosphonoacetate. HHV-6 variants differ in the transcription patterns of their
      genes. U16-U17 originates a splice transcript and is regulated as alpha in HHV-6B
      and as beta in HHV-6A. U91 generates two transcripts, amplified as 476- and 374
      bp PCR fragments. The 476-bp fragment is alpha in HHV-6A-infected cells but beta
      in HHV-6B-infected cells. Conversely, the 374-bp fragment is beta in HHV-6A
      infected cells and alpha in HHV-6B-infected cells. Furthermore, the spliced
      product of U18-U19-U20 (526 bp) is beta in HHV-6A-infected cells, but only a
      partially spliced form (1.9 kb) was detected at late stages of infection in HHV
      6B. HHV-6 transcription was also studied in nonproductive lymphoid cells, and the
      same transcription pattern detected during lytic infection was observed. Also,
      HHV-6 variants maintain the differences in U91, U16-17, and U18-U19-U20. We
      conclude that, as expected from the sequencing data, gene expression is generally
      similar in HHV-6 variants. However, transcription of selected genes in HHV-6A and
      HHV-6B differs with respect to temporal regulation and splicing pattern.
      Furthermore, the identification of viral functions expressed during the different
      stages of lytic replication suggests that reverse transcription-PCR for HHV-6
      genes is a useful diagnostic approach to differentiate between latent and
      productive HHV-6 infection.

PMID- 9557668
TI  - Antiviral activity of the proteasome on incoming human immunodeficiency virus
      type 1.
AB  - Following cell surface receptor binding and membrane fusion, human
      immunodeficiency virus (HIV) virion cores are released in the cytoplasm. Incoming
      viral proteins represent potential targets for cytosolic proteases. We show that
      treatment of target cells with the proteasome inhibitors MG132 and lactacystin
      increased the efficiency of HIV infection. Proteasome inhibitors were active at
      the early steps of the viral cycle. Incoming p24Gag proteins accumulated in the
      cytosol, and larger amounts of proviral DNA were synthesized. In vitro, purified
      20S proteasome degraded HIV virion components. Thus, degradation of incoming
      viral proteins by the proteasome represents an early intracellular defense
      against infection.

PMID- 9557670
TI  - Effect of water-based microencapsulation on protection against EDIM rotavirus
      challenge in mice.
AB  - We determined the capacity of microcapsules formed by the combination of sodium
      alginate, an aqueous anionic polymer, and spermine hydrochloride, an aqueous
      cationic amine, to enhance protection against rotavirus challenge in mice. Adult
      BALB/c mice were orally inoculated with either free or microencapsulated
      rotavirus (simian rotavirus strain RRV) and challenged 6 or 16 weeks later with
      murine rotavirus strain EDIM. Virus-specific humoral immune responses were
      determined at the time of challenge and 4 days after challenge by intestinal
      fragment culture. We found that spermine-alginate microcapsules enhanced
      protection against challenge 16 weeks after immunization but not 6 weeks after
      immunization. Quantities of virus-specific immunoglobulin A produced by small
      intestinal lamina propria lymphocytes were correlated with the degree of
      protection against challenge afforded by spermine-alginate microcapsules.
      Possible mechanisms by which microcapsules enhance protection against rotavirus
      challenge are discussed.

PMID- 9557669
TI  - Involvement of endoplasmic reticulum chaperones in the folding of hepatitis C
      virus glycoproteins.
AB  - The hepatitis C virus (HCV) genome encodes two envelope glycoproteins (E1 and E2)
      which interact noncovalently to form a heterodimer (E1-E2). During the folding
      and assembly of HCV glycoproteins, a large portion of these proteins are trapped
      in aggregates, reducing the efficiency of native E1-E2 complex assembly. To
      better understand this phenomenon and to try to increase the efficiency of HCV
      glycoprotein folding, endoplasmic reticulum chaperones potentially interacting
      with these proteins were studied. Calnexin, calreticulin, and BiP were shown to
      interact with E1 and E2, whereas no interaction was detected between GRP94 and
      HCV glycoproteins. The association of HCV glycoproteins with calnexin and
      calreticulin was faster than with BiP, and the kinetics of interaction with
      calnexin and calreticulin were very similar. However, calreticulin and BiP
      interacted preferentially with aggregates whereas calnexin preferentially
      associated with monomeric forms of HCV glycoproteins or noncovalent complexes.
      Tunicamycin treatment inhibited the binding of HCV glycoproteins to calnexin and
      calreticulin, indicating the importance of N-linked oligosaccharides for these
      interactions. The effect of the co-overexpression of each chaperone on the
      folding of HCV glycoproteins was also analyzed. However, the levels of native E1
      E2 complexes were not increased. Together, our data suggest that calnexin plays a
      role in the productive folding of HCV glycoproteins whereas calreticulin and BiP
      are probably involved in a nonproductive pathway of folding.

PMID- 9557671
TI  - Epizootic hemorrhagic disease: analysis of tissues by amplification and in situ
      hybridization reveals widespread orbivirus infection at low copy numbers.
AB  - A recent outbreak of hemorrhagic fever in wild ruminants in the northwest United
      States was characterized by rapid onset of fever, followed shortly thereafter by
      hemorrhage and death. As a result, a confirmed 1,000 white-tailed deer and
      pronghorn antelope died over the course of 3 months. Lesions were multisystemic
      and included severe edema, congestion, acute vascular necrosis, and hemorrhage.
      Animals that died with clinical signs and/or lesions consistent with hemorrhagic
      fever had antibody to epizootic hemorrhagic disease virus serotype 2 (EHDV-2) by
      radioimmune precipitation but the antibody was limited exclusively to class
      immunoglobulin M. These findings, indicative of acute infection, were
      corroborated by the observation that numerous deer were found dead; however,
      clinically affected deer were rarely seen during the outbreak. Furthermore, only
      in animals with hemorrhagic lesions was EHDV-2 isolated and/or erythrocyte
      associated EHDV-2 RNA detected by serotype-specific reverse transcription (RT)
      PCR. By using a novel RT in situ PCR assay, viral nucleic acid was localized to
      the cytoplasm of large numbers of tissue leukocytes and vascular endothelium in
      tissues with hemorrhage and to vessels, demonstrating acute intimal and medial
      necrosis. Because PCR amplification prior to in situ hybridization was essential
      for detecting EHDV, the virus copy number within individual cells was low, <20
      virus copies. These findings suggest that massive covert infection characterized
      by rapid dissemination of virus facilitates the severe and lethal nature of this
      disease.

PMID- 9557673
TI  - Carbohydrates facilitate correct disulfide bond formation and folding of
      rotavirus VP7.
AB  - It is well established that glycosylation is essential for assembly of enveloped
      viruses, but no information is yet available as to the function of carbohydrates
      on the nonenveloped but glycosylated rotavirus. We show that tunicamycin and,
      more pronouncedly, a combination of tunicamycin and brefeldin A treatment caused
      misfolding of the luminal VP7 protein, leading to interdisulfide bond
      aggregation. While formation of VP7 aggregates could be prevented under reducing
      conditions, they reoccurred in less than 30 min after a shift to an oxidizing
      milieu. Furthermore, while glycosylated VP7 interacted during maturation with
      protein disulfide isomerase, nonglycosylated VP7 did not, suggesting that
      glycosylation is a prerequisite for protein disulfide isomerase interaction.
      While native NSP4, which does not possess S-S bonds, was not dependent on N
      linked glycosylation or on protein disulfide isomerase assistance for maturation,
      nonglycosylated NSP4 was surprisingly found to interact with protein disulfide
      isomerase, further suggesting that protein disulfide isomerase can act both as an
      enzyme and as a chaperone. In conclusion, our data suggest that the major
      function of carbohydrates on VP7 is to facilitate correct disulfide bond
      formation and protein folding.

PMID- 9557674
TI  - A cellular protein binds vaccinia virus late promoters and activates
      transcription in vitro.
AB  - Available evidence indicates that the transcription of the late class of vaccinia
      virus genes requires the participation of several virus-encoded proteins in
      addition to the viral RNA polymerase. In this report we describe the
      identification of a protein present in extracts of uninfected HeLa cells that
      binds avidly to viral late promoter DNA. The protein bound specifically to
      several different vaccinia virus late promoters but not an early nor an
      intermediate promoter. DNase I footprinting localized the protein's binding site
      to nucleotides surrounding the transcriptional start site of the I1L promoter.
      Optimal promoter binding required sequences in the highly conserved TAAAT motif
      at the transcriptional start site as well as sequences immediately upstream;
      however, one variation on the motif's sequence did not affect promoter binding by
      the protein. Partially purified late promoter binding protein (LPBP) was capable
      of stimulating the transcription activity of extracts depleted of LPBP on a late
      promoter-driven template, establishing LPBP as a transcription activator in
      vitro. These results suggest that a cellular protein is responsible for targeting
      vaccinia virus late promoters for initiation of transcription.

PMID- 9557672
TI  - Simian immunodeficiency virus replicates to high levels in sooty mangabeys
      without inducing disease.
AB  - A serologic survey of primates living in a French zoo allowed identification of
      three cases of infection with simian immunodeficiency virus in sooty mangabeys
      (Cercocebus atys) (SIVsm). Viral isolates, which were designated SIVsmFr66,
      SIVsmFr74, and SIVsmFr85, were obtained after short-term culture of mangabey
      lymphoid cells. Phylogenetic analysis of gag and env sequences amplified directly
      from mangabey tissues showed that the three SIVsmFr were genetically close and
      that they constituted a new subtype within the diverse SIVsm-SIVmac-human
      immunodeficiency virus type 2 (HIV-2) group. We could reconstruct the
      transmission events that likely occurred in 1986 between the three animals and
      evaluate the divergence of SIVsmFr sequences since transmission. The estimated
      rate of mutation fixation was 6 x 10(-3) substitutions per site per year, which
      was as high as the rate found for SIVmac infection in macaques. These data
      indicated that SIVsmFr replicated at a high rate in mangabeys, despite the
      nonpathogenic character of infection in this host. The viral load evaluated by
      competitive PCR reached 20,000 viral DNA copies per 10(6) lymph node cells. In
      addition, productively infected cells were readily detected in mangabey lymphoid
      tissues by in situ hybridization. The amounts of viral RNA in plasma ranged from
      10(5) to 10(7) copies per ml. The cell-associated and plasma viral loads were as
      high as those seen in susceptible hosts (humans or macaques) during the
      asymptomatic stage of HIV or SIVmac infections. Thus, the lack of pathogenicity
      of SIVsm for its natural host cannot be explained by limited viral replication or
      by tight containment of viral production.

PMID- 9557675
TI  - Expression kinetics and mapping of the thymidine kinase transcript and an
      immediate-early transcript from channel catfish virus.
AB  - Three transcripts from the terminal repeat of the channel catfish virus (CCV;
      also known as ictalurid herpesvirus 1) genome were mapped by S1 nuclease and
      primer extension analyses as well as by cDNA sequencing. These transcripts, TR3,
      TR5/6, and TR6, are encoded by open reading frame (ORF) 3, ORFs 5 and 6, and ORF
      6, respectively, and correspond to those previously identified by sequence
      analysis (A. J. Davison, Virology 186:9-14, 1992). ORF 5 has previously been
      determined to encode thymidine kinase, but ORF 3 and ORF 6 encode proteins of
      unknown function. Although all three transcripts accumulate to high levels in
      cells infected in the presence of cycloheximide, kinetic analysis demonstrates
      that TR5/6 and TR6 are either early or late transcripts that leak through the
      cycloheximide block. In addition, two transcripts from the terminal repeat of the
      CCV genome that were mapped previously and were thought to be immediate-early in
      character, TR8a/9 and TR9, exhibit kinetics characteristic of early or late
      transcripts. TR3 is an immediate-early transcript that appears to have a very
      short half-life. In the 3' untranslated region of TR3, there are three copies of
      an AU-rich element which has previously been shown to be involved in
      destabilization of the oncogene c-fos and granulocyte/macrophage colony
      stimulating factor mRNAs. mRNA destabilization may represent another mechanism by
      which herpesviruses regulate the rapid switch in expression from immediate-early
      genes to early genes during the transition to the early phase of infection.

PMID- 9557676
TI  - The role of nucleocapsid and U5 stem/A-rich loop sequences in tRNA(3Lys) genomic
      placement and initiation of reverse transcription in human immunodeficiency virus
      type 1.
AB  - We have studied the effect of mutations in the human immunodeficiency virus type
      1 (HIV-1) nucleocapsid (NC) sequence on tRNA(3Lys) genomic placement, i.e., the
      in vivo placement of primer tRNA(3Lys) on the HIV-1 primer binding site (PBS).
      HIV-1 produced from COS cells transfected with wild-type or mutant proviral DNA
      was used in this study. We have found that mutations in the amino acid sequences
      flanking the first Cys-His box in the NC sequence produce the maximum inhibition
      of genomic placement. A similar finding was obtained when the NC-facilitated
      annealing of primer tRNA(3Lys) to the HIV PBS in vitro was studied. However,
      since the genomic placement of tRNA(3Lys) occurs independently of precursor
      protein processing, the NC mutations studied here have probably exerted their
      effect through one or both of the precursor proteins, Pr55gag and/or Pr160(gag
      pol). One mutation in the linker region between the two Cys-His boxes, P31L,
      prevented packaging of both Pr160(gag-pol) and tRNA(3Lys) and prevented the
      genomic placement of tRNA(3Lys). Both packaging and genomic placement were
      rescued by cotransfection with a plasmid coding for wild-type Pr160(gag-pol). For
      other linker mutations [R7R10K11 S, R32G, and S3(32-34)], packaging of Pr160(gag
      pol) and tRNA(3Lys) was not affected, but genomic placement was, and placement
      could not be rescued by cotransfection with plasmids coding for either Pr55gag or
      Pr160(gag-pol). After placement, the initiation of reverse transcription within
      extracellular virions is characterized by a 2-base DNA extension of the placed
      tRNA(3Lys). This process requires precursor processing, and those NC mutations
      which showed the most inhibition of initiation were in either of the two NC Cys
      His boxes. Destabilization of a U5 stem-A-rich loop immediately upstream of the
      PBS (through deletion of four consecutive A's in the loop) did not affect the in
      vivo genomic placement of tRNA(3Lys) but resulted in the presence in the
      extracellular virus of longer cDNA extensions of tRNA(3Lys), with a corresponding
      decrease in the presence of unextended and 2-base-extended tRNA(3Lys).

PMID- 9557677
TI  - Mutational scan of the human immunodeficiency virus type 2 integrase protein.
AB  - Retroviral integrase (IN) cleaves linear viral DNA specifically near the ends of
      the DNA (cleavage reaction) and subsequently couples the processed ends to
      phosphates in the target DNA (integration reaction). In vitro, IN catalyzes the
      disintegration reaction, which is the reverse of the integration reaction.
      Ideally, we would like to test the role of each amino acid in the IN protein. We
      mutagenized human immunodeficiency virus type 2 IN in a random way using PCR
      mutagenesis and generated a set of mutants in which 35% of all residues were
      substituted. Mutant proteins were tested for in vitro activity, e.g., site
      specific cleavage of viral DNA, integration, and disintegration. Changes in 61 of
      the 90 proteins investigated showed no phenotypic effect. Substitutions that
      changed the choice of nucleophile in the cleavage reaction were found. These
      clustered around the active-site residues Asp-116 and Glu-152. We also found
      alterations of amino acids that affected cleavage and integration differentially.
      In addition, we analyzed the disintegration activity of the proteins and found
      substitutions of amino acids close to the dimer interface that enhanced
      intermolecular disintegration activity, whereas other catalytic activities were
      present at wild-type levels. This study shows the feasibility of investigating
      the role of virtually any amino acid in a protein the size of IN.

PMID- 9557678
TI  - Transactivation-competent bovine papillomavirus E2 protein is specifically
      required for efficient repression of human papillomavirus oncogene expression and
      for acute growth inhibition of cervical carcinoma cell lines.
AB  - The papillomavirus E2 proteins can function as sequence-specific transactivators
      or transrepressors of transcription and as cofactors in viral DNA replication. We
      previously demonstrated that acute expression of the bovine papillomavirus type 1
      (BPV1) E2 protein in HeLa and HT-3 cervical carcinoma cell lines greatly reduced
      cellular proliferation by imposing a specific G1/S phase growth arrest. In this
      report, we analyzed the effects of a panel of point mutations in the BPV1 E2
      protein to identify the functional requirements for acute growth inhibition.
      Disruption of E2-specific transactivation by mutations within either the
      transactivation domain or the DNA binding domain severely impaired E2-mediated
      growth inhibition in HeLa and HT-3 cells, even though these mutants retain
      various other E2 activities. This result indicates that functional
      transactivation activity is required for acute E2-mediated growth inhibition.
      HeLa cells, which contain a wild-type p53 gene, and HT-3 cells, which contain a
      transactivation-defective p53 gene, exhibited similar responses to the E2
      mutants, suggesting that identical functions of the E2 protein were required for
      growth arrest regardless of p53 status. Replacement of the E2 transactivation
      domain with that of the herpes simplex virus VP16 generated a chimeric
      transactivator that efficiently stimulated expression of an E2-responsive
      reporter plasmid yet was completely defective for growth inhibition, suggesting
      that an E2-specific transactivation function is required for growth arrest.
      Surprisingly, the transactivation-defective E2 mutants were also markedly
      defective in their ability to repress transcription of the native human
      papillomavirus type 18 (HPV18) E6/E7 oncogenes in HeLa cells and of the HPV18
      promoter present in a transfected reporter plasmid. These mutants were also
      defective in their ability to increase p53 levels. Therefore, efficient
      repression of the HPV18 promoter in HeLa cells is not merely a consequence of the
      binding of an E2 protein to appropriately situated binding sites in the promoter.

PMID- 9557679
TI  - The transmembrane domains of Sindbis virus envelope glycoproteins induce cell
      death.
AB  - Sindbis virus, the prototype alphavirus, kills cells by inducing apoptosis. To
      investigate potential mechanisms by which Sindbis virus induces apoptosis, we
      examined whether specific viral gene products were able to induce cell death.
      Genes encoding the three structural proteins--capsid, the precursor E1 (6K plus
      E1), and the precursor E2 (P62 or E3 plus E2)--were cotransfected with a beta
      galactosidase reporter plasmid in transient-transfection assays in rat prostate
      adenocarcinoma AT3 cells. Cell death, as determined by measuring the loss of blue
      cells, was observed in AT3 cells transfected with 6K plus E1 and with P62 but not
      in cells transfected with capsid. Deletion mutagenesis of P62 indicated that
      large regions of the cytoplasmic domain and extracellular domain were not
      essential for the induction of cell death. However, constructs containing the
      minimal E3 signal sequence fused to the E2 transmembrane domain and the minimal
      E3 signal sequence fused to the E1 transmembrane domain induced death as
      efficiently as full-length P62 and 6K plus E1, whereas no cell death was observed
      after transfection with a control construct containing the E3 signal sequence
      linked to the transmembrane domain of murine CD4. These data demonstrate that
      intracellular expression of the transmembrane domains of the Sindbis virus
      envelope glycoproteins can kill AT3 cells.

PMID- 9557680
TI  - Assembly of the herpes simplex virus capsid: preformed triplexes bind to the
      nascent capsid.
AB  - The herpes simplex virus type 1 (HSV-1) capsid is a T=16 icosahedral shell that
      forms in the nuclei of infected cells. Capsid assembly also occurs in vitro in
      reaction mixtures created from insect cell extracts containing recombinant
      baculovirus-expressed HSV-1 capsid proteins. During capsid formation, the major
      capsid protein, VP5, and the scaffolding protein, pre-VP22a, condense to form
      structures that are extended into procapsids by addition of the triplex proteins,
      VP19C and VP23. We investigated whether triplex proteins bind to the major capsid
      scaffold protein complexes as separate polypeptides or as preformed triplexes.
      Assembly products from reactions lacking one triplex protein were
      immunoprecipitated and examined for the presence of the other. The results showed
      that neither triplex protein bound unless both were present, suggesting that
      interaction between VP19C and VP23 is required before either protein can
      participate in the assembly process. Sucrose density gradient analysis was
      employed to determine the sedimentation coefficients of VP19C, VP23, and VP19C
      VP23 complexes. The results showed that the two proteins formed a complex with a
      sedimentation coefficient of 7.2S, a value that is consistent with formation of a
      VP19C-VP23(2) heterotrimer. Furthermore, VP23 was observed to have a
      sedimentation coefficient of 4.9S, suggesting that this protein exists as a dimer
      in solution. Deletion analysis of VP19C revealed two domains that may be required
      for attachment of the triplex to major capsid-scaffold protein complexes; none of
      the deletions disrupted interaction of VP19C with VP23. We propose that preformed
      triplexes (VP19C-VP23(2) heterotrimers) interact with major capsid-scaffold
      protein complexes during assembly of the HSV-1 capsid.

PMID- 9557681
TI  - Transmission of human T-cell leukemia virus type 1 to mice.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell
      leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis, and
      other diseases. For prevention of the transmission of HTLV-1 and manifestation of
      these diseases, a small-animal model, especially a mouse model, would be useful.
      We injected HTLV-1-producing T cells (MT-2) intraperitoneally into neonatal
      C3H/HeJ mice. While the antibody against HTLV-1 antigens was not detectable in
      C3H/HeJ mice, HTLV-1 provirus was frequently detected in the spleen, lymph nodes,
      and thymus by PCR. HTLV-1 provirus was present at the level of 0 to 30 molecules
      in 10(5) spleen cells at the age of 15 weeks. In addition, a 59-bp flanking
      sequence of the HTLV-1 integration site was amplified from the spleen DNA by
      linker-mediated PCR and was confirmed to be derived from the mouse genome. HTLV-1
      provirus was found in the T-cell fraction of the mouse spleen. These results
      indicate that mice can be infected by HTLV-1 and could serve as an animal model
      for the study of HTLV-1 infection and its pathogenesis in vivo.

PMID- 9557683
TI  - Minimal template requirements for initiation of minus-strand synthesis in vitro
      by the RNA-dependent RNA polymerase of turnip yellow mosaic virus.
AB  - From mutational analysis of the 3'-terminal hairpin of turnip yellow mosaic virus
      (TYMV) RNA and use of nonstructured C-rich RNA templates, we conclude that the
      main determinant in the tRNA-like structure of TYMV RNA for initiation of minus
      strand synthesis by the viral RNA-dependent RNA polymerase (RdRp) is the non-base
      paired 3' ACC(A) end. Base pairing of this 3' end reduces the transcription
      efficiency drastically, and deletion of only the 3'-terminal A residue results in
      a fivefold drop in efficiency. The two C residues of the 3' ACCA end are required
      for efficient transcription, as shown by substitution mutations. However, the 5'
      A residue is not specifically involved in initiation of transcription, as shown
      by substitution mutations. Furthermore, the hairpin stem and loop upstream of the
      3' ACCA end also do not interact with the RdRp in a base-specific way. However,
      for efficient transcription, the hairpin stem should be at least five bp in
      length, while the calculated deltaG value should be less than -10.5 kcal/mol.
      Unexpectedly, the use of nonstructured C-rich RNA templates showed that the RdRp
      can start internally on an NCCN or NUCN sequence. Therefore, a possible function
      of the tRNA-like structure of TYMV RNA may be to prevent internal initiation of
      minus-strand synthesis.

PMID- 9557682
TI  - Cloning of novel isoforms of the human Gli2 oncogene and their activities to
      enhance tax-dependent transcription of the human T-cell leukemia virus type 1
      genome.
AB  - The expression of human T-cell leukemia virus type 1 (HTLV-1) is activated by
      interaction of a viral transactivator protein, Tax, and cellular transcription
      factor, CREB (cyclic AMP response element binding protein), which bind to a 21-bp
      enhancer in the long terminal repeats (LTR). THP (Tax-helping protein) was
      previously determined to enhance the transactivation by Tax protein. Here we
      report novel forms of the human homolog of a member of the Gli oncogene family,
      Gli2 (also termed Gli2/THP), an extended form of a zinc finger protein, THP,
      which was described previously. Four possible isoforms (hGli2 alpha, beta, gamma,
      and delta) are formed by combinations of two independent alternative splicings,
      and all the isoforms could bind to a DNA motif, TRE2S, in the LTR. The longer
      isoforms, alpha and beta, were abundantly expressed in various cell lines
      including HTLV-1-infected T-cell lines. Fusion proteins of the hGli2 isoforms
      with the DNA-binding domain of Gal4 activated transcription when the reporter
      contained a Gal4-binding site and one copy of the 21-bp sequence, to which CREB
      binds. This activation was observed only in the presence of Tax. The 21-bp
      sequence in the reporter was also essential for the activation. These results
      suggest that simultaneous binding of hGli2 and CREB to the respective sites in
      the reporter seems to be critical for Tax protein to activate transcription.
      Consequently, it is probable that the LTR can be regulated by two independent
      signals through hGli2 and CREB, since the LTR contains the 21-bp and TRE2S
      sequences in the vicinity.

PMID- 9557684
TI  - The mouse H-2A region influences the envelope gene structure of tumor-associated
      murine leukemia viruses.
AB  - C57BL/10 (B10) strains congenic at the mouse major histocompatibility locus (H-2)
      were injected with a modified ecotropic SL3-3 murine leukemia virus (MuLV) to
      determine the effect of the H-2 genes on the envelope gene structure of
      recombinant MuLVs. All tested strains rapidly developed T-cell lymphomas, and
      recombinant proviruses were detected in the tumor DNAs by Southern blot. The
      B10.D2 (H-2d), B10.Br (H-2k), B10.Q (H-2q), and B10.RIII (H-2r) strains exhibited
      a TI phenotype in which almost all tumors contained type I recombinants. These
      recombinants characteristically acquire envelope gene sequences from the
      endogenous polytropic viruses but retain the 5' p15E (TM) gene sequences from the
      ecotropic virus. The parental B10 (H-2b) strain, however, had a novel phenotype
      that was designated NS for nonselective. Only 30% of the B10 tumors had
      detectable type I recombinants, whereas a proportion of the others appeared to
      contain type II recombinants that lacked the type I-specific ecotropic p15E gene
      sequences. Studies of other B10 congenic strains with hybrid H-2 loci and
      selected F1 animals revealed that the NS phenotype was regulated by a dominant
      gene(s) that mapped to the A region of H-2b. These results demonstrate that a
      host gene within the major histocompatibility complex can influence the genetic
      evolution of pathogenic retroviruses in vivo.

PMID- 9557685
TI  - Natural isolates of simian virus 40 from immunocompromised monkeys display
      extensive genetic heterogeneity: new implications for polyomavirus disease.
AB  - Simian virus 40 (SV40) DNAs in brain tissue and peripheral blood mononuclear
      cells (PBMCs) of eight simian immunodeficiency virus-infected rhesus monkeys with
      SV40 brain disease were analyzed. We report the detection, cloning, and
      identification of five new SV40 strains following a quadruple testing
      verification strategy. SV40 genomes with archetypal regulatory regions
      (containing a duplication within the G/C-rich regulatory region segment and a
      single 72-bp enhancer element) were recovered from seven animal brains, two
      tissues of which also contained viral genomes with nonarchetypal regulatory
      regions (containing a duplication within the G/C-rich regulatory region segment
      as well as a variable duplication within the enhancer region). In contrast, PBMC
      DNAs from five of six animals had viral genomes with both regulatory region
      types. It appeared, based on T-antigen variable-region sequences, that
      nonarchetypal virus variants arose de novo within each animal. The eighth animal
      exclusively yielded a new type of SV40 strain (SV40-K661), containing a
      protoarchetypal regulatory region (lacking a duplication within the G/C-rich
      segment of the regulatory region and containing one 72-bp element in the enhancer
      region), from both brain tissue and PBMCs. The presence of SV40 in PBMCs suggests
      that hematogenous spread of viral infection may occur. An archetypal version of a
      virus similar to SV40 reference strain 776 (a kidney isolate) was recovered from
      one brain, substantiating the idea that SV40 is neurotropic as well as kidney
      tropic. Indirect evidence suggests that maternal-infant transmission of SV40 may
      have occurred in one animal. These findings provide new insights for human
      polyomavirus disease.

PMID- 9557686
TI  - Infectious molecular clones with the nonhomologous dimer initiation sequences
      found in different subtypes of human immunodeficiency virus type 1 can recombine
      and initiate a spreading infection in vitro.
AB  - Recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been shown
      to be of major importance in the global AIDS pandemic. Viral RNA dimer formation
      mediated by the dimerization initiation sequence (DIS) is believed to be
      essential for viral genomic RNA packaging and therefore for RNA recombination.
      Here, we demonstrate that HIV-1 recombination and replication are not restricted
      by variant DIS loop sequences. Three DIS loop forms found among HIV-1 isolates,
      DIS (CG), DIS (TA), and DIS (TG), when introduced into deletion mutants of HIV-1
      recombined efficiently, and the progeny virions replicated with comparable
      kinetics. A fourth DIS loop form, containing an artificial AAAAAA sequence
      disrupting the putative DIS loop-loop interactions [DIS (A6)], supported
      efficient recombination with DIS loop variants; however, DIS (A6) progeny virions
      exhibited a modest replication disadvantage in mixed cultures. Our studies
      indicate that the nonhomologous DIS sequences found in different HIV-1 subtypes
      are not a primary obstacle to intersubtype recombination.

PMID- 9557687
TI  - Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross
      reactive epitopes on nonstructural proteins following natural secondary dengue
      virus infection.
AB  - We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral
      blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after
      natural symptomatic secondary dengue virus infection. In all four patients
      analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue
      virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk
      cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a
      (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived
      from both patients were cross-reactive with other serotypes of dengue virus. The
      CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and
      the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The
      CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the
      CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221
      to 232 on NS3. These results demonstrate that in Thai patients after symptomatic
      secondary natural dengue infections, CTLs are mainly directed against
      nonstructural proteins and are broadly cross-reactive.

PMID- 9557688
TI  - Chromosome structure and human immunodeficiency virus type 1 cDNA integration:
      centromeric alphoid repeats are a disfavored target.
AB  - Integration of retroviral cDNA into host chromosomal DNA is an essential and
      distinctive step in viral replication. Despite considerable study, the host
      determinants of sites for integration have not been fully clarified. To
      investigate integration site selection in vivo, we used two approaches. (i) We
      have analyzed the host sequences flanking 61 human immunodeficiency virus type 1
      (HIV-1) integration sites made by experimental infection and compared them to a
      library of 104 control sequences. (ii) We have also analyzed HIV-1 integration
      frequencies near several human repeated-sequence DNA families, using a repeat
      specific PCR-based assay. At odds with previous reports from smaller-scale
      studies, we found no strong biases either for or against integration near
      repetitive sequences such as Alu or LINE-1 elements. We also did not find a clear
      bias for integration in transcription units as proposed previously, although
      transcription units were found somewhat more frequently near integration sites
      than near controls. However, we did find that centromeric alphoid repeats were
      selectively absent at integration sites. The repeat-specific PCR-based assay also
      indicated that alphoid repeats were disfavored for integration in vivo but not as
      naked DNA in vitro. Evidently the distinctive DNA organization at centromeres
      disfavors cDNA integration. We also found a weak consensus sequence for host DNA
      at integration sites, and assays of integration in vitro indicated that this
      sequence is favored as naked DNA, revealing in addition an influence of target
      primary sequence.

PMID- 9557689
TI  - The Epstein-Barr virus BARF1 gene encodes a novel, soluble colony-stimulating
      factor-1 receptor.
AB  - Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with infectious
      mononucleosis and several tumors. The BARF1 gene is transcribed early after EBV
      infection from the BamHI A fragment of the EBV genome. Evidence shown here
      indicates that the BARF1 protein is secreted into the medium of transfected cells
      and from EBV-carrying B cells induced to allow lytic replication of the virus.
      Expression cloning identified colony-stimulating factor-1 (CSF-1) as a ligand for
      BARF1. Computer-assisted analyses indicated that subtle amino acid sequence
      homology exists between BARF1 and c-fins, the cellular proto-oncogene that is the
      receptor for CSF-1. Recombinant BARF1 protein was found to be biologically
      active, and it neutralized the proliferative effects of human CSF-1 in a dose
      dependent fashion when assayed in vitro. Since CSF-1 is a pleiotropic cytokine
      best known for its differentiating effects on macrophages, these data suggest
      that BARF1 may function to modulate the host immune response to EBV infection.

PMID- 9557690
TI  - Two types of virus-related particles are found during transmissible
      gastroenteritis virus morphogenesis.
AB  - The intracellular assembly of the transmissible gastroenteritis coronavirus
      (TGEV) was studied in infected swine testis (ST) cells at different postinfection
      times by using ultrathin sections of conventionally embedded infected cells,
      freeze-substitution, and methods for detecting viral proteins and RNA at the
      electron microscopy level. This ultrastructural analysis was focused on the
      identification of the different viral components that assemble in infected cells,
      in particular the spherical, potentially icosahedral internal core, a new
      structural element of the extracellular infectious coronavirus recently
      characterized by our group. Typical budding profiles and two types of virion
      related particles were detected in TGEV-infected cells. While large virions with
      an electron-dense internal periphery and a clear central area are abundant at
      perinuclear regions, smaller viral particles, with the characteristic morphology
      of extracellular virions (exhibiting compact internal cores with polygonal
      contours) accumulate inside secretory vesicles that reach the plasma membrane.
      The two types of virions coexist in the Golgi complex of infected ST cells. In
      nocodazole-treated infected cells, the two types of virions coexist in altered
      Golgi stacks, while the large secretory vesicles filled with virions found in
      normal infections are not detected in this case. Treatment of infected cells with
      the Golgi complex-disrupting agent brefeldin A induced the accumulation of large
      virions in the cisternae that form by fusion of different membranous
      compartments. These data, together with the distribution of both types of virions
      in different cellular compartments, strongly suggest that the large virions are
      the precursors of the small viral particles and that their transport through a
      functional Golgi complex is necessary for viral maturation.

PMID- 9557691
TI  - T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to
      stromal cell-derived factor 1alpha contains mutations in the envelope gp120 but
      does not show a switch in coreceptor use.
AB  - The NL4.3 T-cell-line-tropic human immunodeficiency virus type 1 strain is
      sensitive to the CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha),
      the natural ligand for CXC chemokine receptor 4 (CXCR4); the 50% inhibitory
      concentration (IC50) in MT-4 cells is 130 ng/ml. We generated resistant virus
      through passaging of the virus in the presence of increasing concentrations of
      SDF-1alpha. After 24 passages, the virus was no longer sensitive to SDF-1alpha
      (SDF-1alpha(res) virus) (IC50, >2 microg/ml) and became resistant to SDF-1beta
      (IC50, >2 microg/ml) and to a specific CXCR4 monoclonal antibody (IC50, >20
      microg/ml). The SDF-1alpha(res) virus was about 10-fold less sensitive than the
      wild-type virus to the bicyclam AMD3100, a specific CXCR4 antagonist. The SDF
      1alpha(res) virus contained the following mutations in the gp120 molecule: N106K
      in the V1 loop; S134N and F145L in the V2 loop; F245I in the C2 loop; K269E,
      Q278H, I288V, and N293D in the V3 loop; a deletion of 5 amino acids (FNSTW) at
      positions 364 to 368 in the V4 loop; and R378T in the CD4 binding domain.
      Replication of the NL4.3 wild-type virus and the SDF-1alpha(res) virus was
      demonstrated in U87 cells that coexpressed CD4 and CXCR4 (U87.CD4.CXCR4) but not
      in U87.CD4.CCR5 cells. Thus, the resistant virus was not able to switch to the CC
      chemokine receptor 5 (CCR5) coreceptor (the main coreceptor for macrophage-tropic
      viruses). The SDF-1alpha(res) virus replicated in HOS.CD4 cells expressing CCR1,
      CCR2b, CCR3, CCR4, CCR5, and CXCR4 but also in HOS.CD4.pBABE cells. However, all
      HOS transfectant cells expressed a low level of CXCR4. Neither of the two virus
      strains was able to infect HOS.CXCR4 or HOS.CCR5 transfectants, demonstrating the
      necessity of the CD4 receptor. The T-cell-line-tropic SDF-1alpha(res) virus was
      thus able to overcome the inhibitory effect of SDF-1alpha through mutations in
      gp120 but still needed CXCR4 to enter the cells.

PMID- 9557692
TI  - The 30-base-pair deletion in Chinese variants of the Epstein-Barr virus LMP1 gene
      is not the major effector of functional differences between variant LMP1 genes in
      human lymphocytes.
AB  - One group of sequence variants of Epstein-Barr virus is characterized by a 10
      amino-acid deletion within the CTAR-2 functional domain of the latent membrane
      protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the
      viral oncogene in rodent fibroblasts was recently demonstrated. We examined the
      effect of this deletion upon LMP1 function in four human lymphoid cell lines by
      using three natural variants of LMP1: the prototype B95.8 gene and the CAO and
      AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1 deleted.
      These experiments revealed that LMP1-mediated upregulation of CD40 and CD54 was
      markedly impaired (by 60 to 90%) with CAO-LMP1 compared with B95.8-LMP1. In
      contrast, the function of AG876-LMP1 was indistinguishable from that of B95.8
      LMP1 in two lines and was only slightly impaired in the other two lines.
      Activation of NF-kappaB by CAO-LMP1 was not impaired in any of the lines; rather,
      activation of an NF-kappaB reporter by CAO-LMP1 was consistently about twofold
      greater than the activation with B95.8- or AG876-LMP1. Therefore, while the CAO
      LMP1 is functionally distinct from the prototype B95.8-LMP1 in human lymphocytes,
      the 10-amino-acid deletion appears not to be directly responsible. This
      conclusion was confirmed by using a B95.8-LMP1 mutant with codons 343 to 352
      deleted and chimerae of CAO- and B95.8-LMP1 in which the CTAR-2 domains of these
      genes were exchanged. Sequences outside the CTAR-2 domain were implicated in the
      distinct functional characteristics of CAO-LMP1 in human lymphoid cells.

PMID- 9557693
TI  - Control of adenovirus early gene expression during the late phase of infection.
AB  - The adenovirus gene regulatory program occurs in two distinct phases, as defined
      by the onset of DNA replication. During the early phase, the E1A, E1B, E2, E3,
      and E4 genes are maximally expressed, while the major late promoter (MLP) is
      minimally expressed and transcription is attenuated. After the onset of DNA
      replication, the IVa2 and pIX genes are expressed at high levels, transcription
      from the MLP is unattenuated and fully activated, and early gene expression is
      repressed. Although the cis elements and trans-acting factors responsible for the
      late-phase activation of the MLP have been identified and characterized and the
      role of DNA replication in activation has been established, the mechanism(s)
      underlying the commensurate decrease in early gene expression has yet to be
      elucidated. The results of this study demonstrate that this decrease depends on a
      fully functional MLP. Specifically, virus mutants with severely deficient
      transcription from the MLP exhibit a marked increase in expression of the E1A,
      E1B, and E2 early genes. These increases were observed at the level of
      transcription initiation, mRNA accumulation, and protein production. In addition,
      expression from the late gene pIX, which is not contained within the major late
      transcription unit (MLTU), is also markedly increased. To begin the analysis of
      the mechanisms underlying these late-phase effects, mixed-infection experiments
      with mutant and wild-type viruses were performed. The results show that the
      effects on early gene expression, as measured both at the protein and RNA levels,
      are mediated in trans and not in cis. These observations are consistent either
      with a model in which one or more late protein products encoded by the MLTU acts
      as a repressor of early gene expression or with one in which the wild-type MLP
      competes with early promoters for limiting transcription factors.

PMID- 9557694
TI  - Retrotransposition of nonviral RNAs in an avian packaging cell line.
AB  - Retroviruses produced from the quail packaging cell line SE21Q1b predominantly
      contain cellular RNAs instead of viral RNAs. These RNAs can be reverse
      transcribed and integrated into the genomes of newly infected cells and are
      thereafter referred to as newly formed retrogenes. We investigated whether
      retrogene formation can occur within SE21Q1b cells themselves and whether this
      occurs intracellularly or via extracellular reinfection. By using packaging cell
      line mutants derived from the SE21Q1b provirus and selectable reporter
      constructs, we found that the process requires envelope glycoproteins and a
      retroviral packaging signal. Our results suggest that extracellular reinfection
      is the primary route of retrotransposition of nonviral RNAs.

PMID- 9557695
TI  - A broad range of chemokine receptors are used by primary isolates of human
      immunodeficiency virus type 2 as coreceptors with CD4.
AB  - Like human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency
      virus (SIV), HIV-2 requires a coreceptor in addition to CD4 for entry into cells.
      HIV and SIV coreceptor molecules belong to a family of seven-transmembrane-domain
      G-protein-coupled receptors. Here we show that primary HIV-2 isolates can use a
      broad range of coreceptor molecules, including CCR1, CCR2b, CCR3, CCR4, CCR5, and
      CXCR4. Despite broad coreceptor use, the chemokine ligand SDF-1 substantially
      blocked HIV-2 infectivity of peripheral blood mononuclear cells, indicating that
      its receptor, CXCR4, was the predominant coreceptor for infection of these cells.
      However, expression of CXCR4 together with CD4 on some cell types did not confer
      susceptibility to infection by all CXCR4-using virus isolates. These data
      therefore indicate that another factor(s) influences the ability of HIV-2 to
      replicate in human cell types that express the appropriate receptors for virus
      entry.

PMID- 9557696
TI  - Secondary structures in the capsid protein coding sequence and 3' nontranslated
      region involved in amplification of the tobacco etch virus genome.
AB  - The 3'-terminal 350 nucleotides of the tobacco etch potyvirus (TEV) genome span
      the end of the capsid protein (CP)-coding sequence and the 3' nontranslated
      region (NTR). The CP-coding sequence within this region contains a 105-nucleotide
      cis-active element required for genome replication (S. Mahajan, V. V. Dolja, and
      J. C. Carrington, J. Virol. 70:4370-4379, 1996). To investigate the sequence and
      secondary structure requirements within the CP cis-active region and the 3' NTR,
      a systematic linker-scanning mutagenesis analysis was done. Forty-six mutations,
      each with two to six nucleotide substitutions, were introduced at consecutive
      hexanucleotide positions in the genome of a recombinant TEV strain expressing a
      reporter protein (beta-glucuronidase). Genome amplification activity of each
      mutant in the protoplast cell culture system was measured. Mutations that
      severely debilitated genome amplification were identified throughout the CP
      coding cis-active sequence and at several distinct locations within the 3' NTR.
      However, based on a computer model of RNA folding, mutations that had the most
      severe effects mapped to regions that were predicted to form base-paired
      secondary structures. Linker-scanning mutations predicted to affect either strand
      of a base-paired structure within the CP-coding cis-active sequence, a base
      paired structure between two segments of the CP-coding cis-active sequence and a
      contiguous 14-nucleotide segment of the 3' NTR, and a base-paired structure near
      the 3' terminus of the 3' NTR inactivated genome amplification. Compensatory
      mutations that restored base pair interactions in each of these regions restored
      amplification activity, although to differing levels depending on the structure
      restored. These data reveal that the 3' terminus of the TEV genome consists of a
      series of functionally discrete sequences and secondary structures and that the
      CP-coding sequence and 3' NTR are coadapted for genome amplification function
      through a requirement for base pair interactions.

PMID- 9557697
TI  - Recombinant vaccinia virus coexpressing the F protein of respiratory syncytial
      virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV
      specific memory cytotoxic T lymphocytes, whereas priming is diminished in the
      presence of high levels of IL-2 or gamma interferon.
AB  - In order to investigate if immune responses to the fusion (F) protein of
      respiratory syncytial virus (RSV) could be influenced by cytokines, recombinant
      vaccinia viruses (rVV) carrying both the F gene of RSV and the gene for murine
      interleukin-2 (IL-2), IL-4, or gamma interferon (IFN-gamma) were constructed. In
      vitro characterization of rVV revealed that insertion of the cytokine gene into
      the VP37 locus of the vaccinia virus genome resulted in 100- to 1,000-fold higher
      expression than insertion of the same gene into the thymidine kinase (TK) locus.
      In comparison, only a two- to fivefold difference in the level of expression of
      the F protein was observed when the gene was inserted into either of these two
      loci. Mice vaccinated with rVV expressing the F protein and high levels of IL-2
      or IFN-gamma cleared rVV more rapidly than mice inoculated with a control rVV and
      developed only low levels of RSV-specific serum antibody. In addition, these
      recombinants were much less effective at priming RSV-specific memory cytotoxic T
      lymphocytes (CTL) and IFN-gamma production by spleen cells than rVV expressing
      the F protein alone. In contrast, mice vaccinated with rVV expressing high levels
      of IL-4 showed signs of delayed rVV clearance. RSV-specific serum antibody
      responses were biased in favor of immunoglobulin G1 (IgG1) in these mice, as
      there was a significant reduction in IgG2a antibody responses compared with serum
      antibody responses in mice vaccinated with rVV expressing the F protein alone.
      However, vaccination with rVV expressing the F protein together with high levels
      of IL-4 did not alter the development of RSV-specific memory CTL or IFN-gamma
      production by RSV-restimulated splenocytes.

PMID- 9557698
TI  - Characterization of a human foamy virus 170-kilodalton Env-Bet fusion protein
      generated by alternative splicing.
AB  - Primate foamy viruses (FVs) express, in addition to the 130-kDa envelope protein,
      a 170-kDa glycoprotein, which reacts with antisera specific for the envelope and
      Bel proteins. We determined the exact nature of this 170-kDa glycoprotein by
      using the molecularly cloned human FV (HFV). Radioimmunoprecipitation analysis of
      293T cells transfected with appropriate expression constructs by using antisera
      specific for the HFV Env, Bel1, and Bel2 proteins, as well as reverse
      transcription-PCR analysis of HFV-infected cells, demonstrated that this protein
      is an Env-Bet fusion protein that is secreted into the supernatant. However, it
      is only loosely associated, or not associated, with viral particles. gp170 is
      generated by an alternatively spliced Env mRNA using a splice donor and splice
      acceptor pair localized within the env open reading frame (ORF), which is
      normally used to generate Bell and Bet transcripts derived from the internal
      promoter within the env ORF. gp170 is expressed at a level 30 to 50% of the Env
      precursor gp130. However, it alone does not confer infectivity to HFV particles,
      because capsids derived from proviruses expressing only the gp170 were not
      released into the supernatant. In contrast, viruses derived from proviral clones
      deficient in gp170 expression showed similar in vitro infectivity and replication
      kinetics to wild-type virus. Furthermore, both types of viruses were inactivated
      to a similar extent by neutralizing sera, indicating that shedding of gp170
      probably does not affect the humoral immune response in the infected host.

PMID- 9557699
TI  - A proline-rich motif (PPPY) in the Gag polyprotein of Mason-Pfizer monkey virus
      plays a maturation-independent role in virion release.
AB  - Virus assembly represents one of the last steps in the retrovirus life cycle.
      During this process, Gag polyproteins assemble at specific sites within the cell
      to form viral capsids and induce membrane extrusion (viral budding) either as
      assembly progresses (type C virus) or following formation of a complete capsid
      (type B and type D viruses). Finally, the membrane must undergo a fusion event to
      pinch off the particle in order to release a complete enveloped virion.
      Structural elements within the MA region of the Gag polyprotein define the route
      taken to the plasma membrane and direct the process of virus budding. Results
      presented here suggest that a distinct region of Gag is necessary for virus
      release. The pp24 and pp16 proteins of the type D retrovirus Mason-Pfizer monkey
      virus (M-PMV) are phosphoproteins that are encoded in the gag gene of the virus.
      The pp16 protein is a C-terminally located cleavage product of pp24 and contains
      a proline-rich motif (PPPY) that is conserved among the Gag proteins of a wide
      variety of retroviruses. By performing a functional analysis of this coding
      region with deletion mutants, we have shown that the pp16 protein is dispensable
      for capsid assembly but essential for virion release. Moreover, additional
      experiments indicated that the virus release function of pp16 was abolished by
      the deletion of only the PPPY motif and could be restored when this motif alone
      was reinserted into a Gag polyprotein lacking the entire pp16 domain. Single
      amino-acid substitutions for any of the residues within this motif confer a
      similar virion release-defective phenotype. It is unlikely that the function of
      the proline-rich motif is simply to inhibit premature activation of protease,
      since the PPPY deletion blocked virion release in the context of a protease
      defective provirus. These results demonstrate that in type D retroviruses a PPPY
      motif plays a key role in a late stage of virus budding that is independent of
      and occurs prior to virion maturation.

PMID- 9557700
TI  - The putative alpha helix 2 of human immunodeficiency virus type 1 Vpr contains a
      determinant which is responsible for the nuclear translocation of proviral DNA in
      growth-arrested cells.
AB  - Several viral determinants were shown to play a role in the ability of human
      immunodeficiency virus type 1 (HIV-1) to infect nondividing cells. In particular,
      Vpr and Gag matrix (MA) were recognized to be involved in the nuclear transport
      of the viral preintegration complex. The goal of the present study was to
      evaluate the ability of isogenic HIV-1 viruses harboring different vpr and gag
      genes to infect nondividing cells. Surprisingly, our results reveal that the
      introduction of mutations in the MA nuclear localization signal marginally
      affected the ability of proviruses to establish infection in growth-arrested HeLa
      or MT4 cells. In contrast, we show that in our experimental system, the absence
      of Vpr expression leads to a reduction in viral infectivity and production which
      correlates with a decrease in the synthesis and nuclear transport of proviral DNA
      as determined by PCR analysis. Moreover, our data demonstrate that this reduction
      of viral replication is also observed with proviruses containing different
      mutated Vpr alleles. In particular, the Vpr Q65E mutant, which contains a
      substitution in the second predicted amphipathic alpha-helical structure located
      in the central region of the protein, is associated with an impairment of the
      protein nuclear localization and a concomitant reduction of the nuclear transport
      of proviral DNA. The results of this study provide evidence that a putative
      amphipathic alpha-helical structure in the central region of Vpr contains a
      determinant involved in the nuclear translocation of the preintegration complex
      in nondividing cells.

PMID- 9557701
TI  - Role of matrix in an early postentry step in the human immunodeficiency virus
      type 1 life cycle.
AB  - The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been
      reported to play a crucial role in the targeting of the Gag polyprotein precursor
      to the plasma membrane and in the incorporation of viral envelope glycoproteins
      into budding virions. In this report, we present evidence that mutation of a
      highly conserved Leu at matrix amino acid 20 blocks or markedly delays virus
      replication in a range of cell types, including T-cell lines, primary human
      peripheral blood mononuclear cells, and monocyte-derived macrophages. These
      mutations do not impair virus assembly and release, RNA encapsidation, or
      envelope glycoprotein incorporation into virions but rather cause significant
      defects in an early step in the virus life cycle, as measured by single-cycle
      infectivity assays and the analysis of viral DNA synthesis early postinfection.
      This infectivity defect is independent of the type of envelope glycoprotein
      carried on mutant virions; similar results are obtained in pseudotyping
      experiments using wild-type or truncated HIV-1 envelope glycoproteins, the
      amphotropic murine leukemia virus envelope, or the vesicular stomatitis G
      protein. Intriguingly, matrix residue 20 mutations also increase the apparent
      binding of Gag to membrane, accelerate the kinetics of Gag processing, and induce
      defects in endogenous reverse transcriptase activity without affecting virion
      density or morphology. These results help elucidate the function of matrix in HIV
      1 replication.

PMID- 9557702
TI  - Bovine viral diarrhea virus strain Oregon: a novel mechanism for processing of
      NS2-3 based on point mutations.
AB  - Bovine viral diarrhea virus (BVDV) isolates can either be cytopathogenic (cp) or
      noncytopathogenic (noncp). While both biotypes express the nonstructural protein
      NS2-3, generation of NS3 strictly correlates with the cp phenotype. The
      production of NS3 is usually caused by cp specific genome alterations, which were
      found to be due to RNA recombination. Molecular analyses of the cp BVDV strain
      Oregon revealed that it does not possess such genome alterations but nevertheless
      is able to generate NS3 via processing of NS2-3. The NS3 serine protease is not
      involved in this cleavage, which, according to protein sequencing, occurs between
      amino acids 1589 and 1590 of the BVDV Oregon polyprotein. Transient-expression
      studies indicated that important information for the cleavage of NS2-3 is located
      within NS2. This was verified by expression of chimeric constructs containing
      cDNA fragments derived from BVDV Oregon and a noncp BVDV. It could be shown that
      the C-terminal part of NS2 plays a crucial role in NS2-3 cleavage. These data,
      together with results obtained by site-specific exchanges in this region,
      revealed a new mechanism for NS2-3 processing which is based on point mutations
      within NS2.

PMID- 9557703
TI  - Insertion of a sequence encoding light chain 3 of microtubule-associated proteins
      1A and 1B in a pestivirus genome: connection with virus cytopathogenicity and
      induction of lethal disease in cattle.
AB  - Pestiviruses represent the first RNA viruses for which recombination with
      cellular protein-coding sequences has been reported. As a result of such
      recombinations cytopathogenic (cp) pestiviruses can develop from
      noncytopathogenic (noncp) viruses. In the case of bovine viral diarrhea virus
      (BVDV), the generation of cp mutants is linked to the induction of the lethal
      syndrome mucosal disease (MD) in cattle. The cp BVDV JaCP was isolated from an
      animal which had come down with MD. The genome of JaCP contains a novel kind of
      cellular insertion (LC3*) which is flanked by duplicated pestivirus sequences.
      Neither insertion nor duplication is present in the genome of the accompanying
      noncp virus JaNCP. As part of the viral polyprotein, the insertion in the JaCP
      genome is translated into a polypeptide almost identical to a fragment of light
      chain 3, a subunit of the microtubule-associated proteins 1A and 1B from the rat.
      Transient-expression studies revealed that the LC3* sequence is able to induce an
      additional cleavage of the viral polyprotein. The respective cleavage occurs
      directly downstream of the LC3*-encoded sequence and is not dependent on the NS3
      serine protease. Insertion of LC3* into an infectious noncp pestivirus cDNA clone
      without duplicated viral sequences resulted in recovery of a defective cp virus
      able to replicate only in the presence of a noncp helper virus. In contrast,
      introduction of both insertion and duplication led to an autonomously replicating
      cp virus.

PMID- 9557704
TI  - Identification of a novel cellular TPR-containing protein, SGT, that interacts
      with the nonstructural protein NS1 of parvovirus H-1.
AB  - The nonstructural protein NS1 of autonomous parvoviruses is essential for viral
      DNA amplification and gene expression and is also the major cytopathic effector
      of these viruses. NS1 acts as nickase, helicase, and ATPase and upregulates P38
      driven transcription of the capsid genes. We report here the identification of a
      novel cellular protein that interacts with NS1 from parvovirus H-1 and which we
      termed SGT, for small glutamine-rich tetratricopeptide repeat (TPR)-containing
      protein. The cDNA encoding full-length SGT was isolated through a two-hybrid
      screen with, as bait, the truncated NS1dlC69 polypeptide, which lacks the C
      terminal transactivation domain of NS1. Full-length NS1 and SGT interacted in the
      two-hybrid system and in an in vitro interaction assay. Northern blot analysis
      revealed one major transcript of about 2 kb that was present in all rat tissues
      investigated. Rat sgt cDNA coded for 314 amino acids, and the protein migrated in
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent
      molecular mass of 34 kDa. SGT could be detected in both the nucleus and the
      cytoplasm of rat cells, as determined by indirect immunofluorescence analysis and
      Western blotting of fractionated cellular extracts with an affinity-purified
      antiserum raised against recombinant SGT (AC1.1). In H-1 virus-infected rat and
      human cells, compared to mock-infected controls, differences in the migration of
      SGT polypeptides were revealed after Western blot analysis of total cellular
      extracts. Moreover, the transient expression of NS proteins was sufficient to
      induce SGT modification. These results show that cellular SGT, which we have
      identified as an NS1-interacting protein, is modified by parvovirus infection as
      well as NS expression.

PMID- 9557705
TI  - Forced evolution reveals the importance of short open reading frame A and
      secondary structure in the cauliflower mosaic virus 35S RNA leader.
AB  - Cauliflower mosaic virus pregenomic 35S RNA begins with a long leader sequence
      containing an extensive secondary structure and up to nine short open reading
      frames (sORFs), 2 to 35 codons in length. To test whether any of these sORFs are
      required for virus viability, their start codons were mutated either individually
      or in various combinations. The resulting viral mutants were tested for
      infectivity on mechanically inoculated turnip plants. Viable mutants were
      passaged several times, and the stability of the introduced mutations was
      analyzed by PCR amplification and sequencing. Mutations at the 5'-proximal sORF A
      and in the center of the leader resulted in delayed symptom development and in
      the appearance of revertants. In the central leader region, the predicted
      secondary structure, rather than the sORF organization, was restored, while true
      reversions or second-site substitutions in response to mutations of sORF A
      restored this sORF. Involvement of sORF A and secondary structure of the leader
      in the virus replication cycle, and especially in translation of the 35S RNA via
      ribosome shunting, is discussed.

PMID- 9557706
TI  - Recombinant vaccine-induced protection against the highly pathogenic simian
      immunodeficiency virus SIV(mac251): dependence on route of challenge exposure.
AB  - Vaccine protection from infection and/or disease induced by highly pathogenic
      simian immunodeficiency virus (SIV) strain SIV(mac251) in the rhesus macaque
      model is a challenging task. Thus far, the only approach that has been reported
      to protect a fraction of macaques from infection following intravenous challenge
      with SIV(mac251) was the use of a live attenuated SIV vaccine. In the present
      study, the gag, pol, and env genes of SIV(K6W) were expressed in the NYVAC
      vector, a genetically engineered derivative of the vaccinia virus Copenhagen
      strain that displays a highly attenuated phenotype in humans. In addition, the
      genes for the alpha and beta chains of interleukin-12 (IL-12), as well as the IL
      2 gene, were expressed in separate NYVAC vectors and inoculated intramuscularly,
      in conjunction with or separate from the NYVAC-SIV vaccine, in 40 macaques. The
      overall cytotoxic T-lymphocyte (CTL) response was greater, at the expense of
      proliferative and humoral responses, in animals immunized with NYVAC-SIV and
      NYVAC-IL-12 than in animals immunized with the NYVAC-SIV vaccine alone. At the
      end of the immunization regimen, half of the animals were challenged with
      SIV(mac251) by the intravenous route and the other half were exposed to
      SIV(mac251) intrarectally. Significantly, five of the eleven vaccinees exposed
      mucosally to SIV(mac251) showed a transient peak of viremia 1 week after viral
      challenge and subsequently appeared to clear viral infection. In contrast, all 12
      animals inoculated intravenously became infected, but 5 to 6 months after viral
      challenge, 4 animals were able to control viral expression and appeared to
      progress to disease more slowly than control animals. Protection did not appear
      to be associated with any of the measured immunological parameters. Further
      modulation of immune responses by coadministration of NYVAC-cytokine recombinants
      did not appear to influence the outcome of viral challenge. The fact that the
      NYVAC-SIV recombinant vaccine appears to be effective per se in the animal model
      that best mirrors human AIDS supports the idea that the development of a highly
      attenuated poxvirus-based vaccine candidate can be a valuable approach to
      significantly decrease the spread of human immunodeficiency virus (HIV) infection
      by the mucosal route.

PMID- 9557707
TI  - Adenovirus type 12-induced fragility of the human RNU2 locus requires p53
      function.
AB  - Adenovirus type 12 (Ad12) infection of human cells induces four chromosomal
      fragile sites corresponding to the U1 small nuclear RNA (snRNA) genes (the RNU1
      locus), the U2 snRNA genes (RNU2), the U1 snRNA pseudogenes (PSU1), and the 5S
      rRNA genes (RN5S). Ad12-induced fragility of the RNU2 locus requires U2 snRNA
      transcriptional regulatory elements and viral early functions but not viral
      replication or integration, or chromosomal sequences flanking the RNU2 locus. We
      now show that Ad12 cannot induce the RNU1, RNU2, or PSU1 fragile sites in Saos-2
      cells lacking the p53 and retinoblastoma (Rb) proteins but that viral induction
      of fragility is rescued in these cells when the expression of wild-type p53 or
      selected hot-spot mutants (i.e., V143A, R175H, R248W, and R273H) is restored by
      transient expression or stable retroviral transduction. We also observed weak
      constitutive fragility of the RNU1 and RNU2 loci in cells belonging to xeroderma
      pigmentosum complementation groups B and D (XPB and XPD) which are partially
      defective in the ERCC2 (XPD) and ERCC3 (XPB) helicase activities shared between
      the repairosome and the RNA polymerase H basal transcription factor TFIIH. We
      propose a model for Ad12-induced chromosome fragility in which interaction of p53
      with the Ad12 E1B 55-kDa transforming protein (and possibly E4orf6) induces a p53
      gain of function which ultimately perturbs the RNA polymerase II basal
      transcription apparatus. The p53 gain of function could interfere with chromatin
      condensation either by blocking mitotic shutdown of U1 and U2 snRNA transcription
      or by phenocopying global or local DNA damage. Specific fragilization of the
      RNU1, RNU2, and PSU1 loci could reflect the unusually high local concentration of
      strong transcription units or the specialized nature of the U1 and U2 snRNA
      transcription apparatus.

PMID- 9557708
TI  - The envelope protein encoded by the A33R gene is required for formation of actin
      containing microvilli and efficient cell-to-cell spread of vaccinia virus.
AB  - The vaccinia virus (VV) A33R gene encodes a highly conserved 23- to 28-kDa
      glycoprotein that is specifically incorporated into the viral outer envelope. The
      protein is expressed early and late after infection, consistent with putative
      early and late promoter sequences. To determine the role of the protein, two
      inducible A33R mutants were constructed, one with the late promoter and one with
      the early and late A33R promoter elements. Decreased A33R expression was
      associated with small plaques that formed comets in liquid medium. Using both an
      antibiotic resistance gene and a color marker, an A33R deletion mutant,
      vA33delta, was isolated, indicating that the A33R gene is not essential for VV
      replication. The plaques formed by vA33delta, however, were tiny, indicating that
      the A33R protein is necessary for efficient cell-to-cell spread. Rescue of the
      large-plaque phenotype was achieved by inserting a new copy of the A33R gene into
      the thymidine kinase locus, confirming the specific genetic basis of the
      phenotype. Although there was a reduction in intracellular virus formed in cells
      infected with vA33delta, the amount of infectious virus in the medium was
      increased. The virus particles in the medium had the buoyant density of
      extracellular enveloped viruses (EEV). Additionally, amounts of vA33delta cell
      associated extracellular enveloped viruses (CEV) were found to be normal.
      Immunogold electron microscopy of cells infected with vA33delta demonstrated the
      presence of the expected F13L and B5R proteins in wrapping membranes and EEV;
      however, fully wrapped vA33delta intracellular enveloped viruses (IEV) were rare
      compared to partially wrapped particles. Specialized actin tails that propel IEV
      particles to the periphery and virus-tipped microvilli (both common in wild-type
      infected cells) were absent in cells infected with vA33delta. This is the first
      deletion mutant in a VV envelope gene that produces at least normal amounts of
      fully infectious EEV and CEV and yet has a small-plaque phenotype. These data
      support a new model for VV spread, emphasizing the importance of virus-tipped
      actin tails.

PMID- 9557710
TI  - Transduction of dendritic cells by DNA viral vectors directs the immune response
      to transgene products in muscle fibers.
AB  - Immune responses to vector-corrected cells have limited the application of gene
      therapy for treatment of chronic disorders such as inherited deficiency states.
      We have found that recombinant adeno-associated virus (AAV) efficiently
      transduces muscle fibers in vivo without activation of cellular and humoral
      immunity to neoantigenic transgene products such as beta-galactosidase, which
      differs from the experience with recombinant adenovirus, where vibrant T-cell
      responses to the transgene product destroy the targeted muscle fibers. T cells
      activated following intramuscular administration of adenovirus expressing lacZ
      (AdlacZ) can destroy AAVlacZ-transduced muscle fibers, indicating a prior state
      of immunologic nonresponsiveness in the context of AAV gene therapy. Adoptive
      transfer of dendritic cells infected with AdlacZ leads to immune mediated
      elimination of AAVlacZ-transduced muscle fibers. AAVlacZ-transduced antigen
      presenting cells fail to demonstrate beta-galactosidase activity and are unable
      to elicit transgene immunity in adoptive transfer experiments. These studies
      indicate that vector-mediated transduction of dendritic cells is necessary for
      cellular immune responses to muscle gene therapy, a step which AAV avoids,
      providing a useful biological niche for its use in gene therapy.

PMID- 9557709
TI  - A tandem array of minimal U1 small nuclear RNA genes is sufficient to generate a
      new adenovirus type 12-inducible chromosome fragile site.
AB  - Infection of human cells with adenovirus serotype 12 (Ad12) induces metaphase
      fragility of four, and apparently only four, chromosomal loci. Surprisingly, each
      of these four loci corresponds to a cluster of genes encoding a small abundant
      structural RNA: the RNU1 and RNU2 loci contain tandemly repeated genes encoding
      U1 and U2 small nuclear RNAs (snRNAs), respectively; the PSU1 locus is a cluster
      of degenerate U1 genes; and the RN5S locus contains the tandemly repeated genes
      encoding 5S rRNA. These observations suggested that high local levels of
      transcription, in combination with Ad12 early functions, can interfere with
      metaphase chromatin packing. In support of this hypothesis, we and others found
      that an artificial tandem array of transcriptionally active, but not inactive, U2
      snRNA genes would generate a novel Ad12-inducible fragile site. Although U1 and
      U2 snRNA are both transcribed by RNA polymerase II and share similar enhancer,
      promoter, and terminator signals, the human U1 promoter is clearly more complex
      than that of U2. In addition, the natural U1 tandem repeat unit exceeds 45 kb,
      whereas the U2 tandem repeat unit is only 6.1 kb. We therefore asked whether an
      artificial array of minimal U1 genes would also generate a novel Ad12-inducible
      fragile site. The exogenous U1 genes were marked by an innocuous U72C point
      mutation within the U1 coding region so that steady-state levels of U1 snRNA
      derived from the artificial array could be quantified by a simple primer
      extension assay. We found that the minimal U1 genes were efficiently expressed
      and were as effective as minimal U2 genes in generating a novel Ad12-inducible
      fragile site. Thus, despite significant differences in promoter architecture and
      overall gene organization, the active U1 transcription units suffice to generate
      a new virally inducible fragile site.

PMID- 9557711
TI  - Increased misincorporation fidelity observed for nucleoside analog resistance
      mutations M184V and E89G in human immunodeficiency virus type 1 reverse
      transcriptase does not correlate with the overall error rate measured in vitro.
AB  - Nucleoside analog-resistant variants of human immunodeficiency virus type 1 (HIV
      1) reverse transcriptase (RT) that displayed higher in vitro polymerase fidelity
      were previously identified via nucleotide insertion and mispair extension assays.
      To evaluate the contribution of increased nucleotide insertion and primer
      extension fidelities on the overall error rate of HIV-1 RT, we have measured the
      impact of two such mutations, E89G and M184V, on DNA copying fidelity in an M13
      phage-based forward mutation assay. Using this assay, we observed mutation
      frequencies of 8.60 x 10(-3), 6.26 x 10(-3), 5.53 x 10(-3), and 12.30 x 10(-3)
      for wild-type, E89G, M184V, and double-mutant E89G/M184V HIV-1 RTs, respectively.
      Therefore, the overall polymerase fidelities of wild-type, E89G, M184V, and
      E89G/M184V HIV-1 RTs are similar (less than twofold differences) for DNA
      dependent DNA synthesis. Thus, rather large increases in fidelity of
      deoxynucleoside triphosphate insertion and mispair extension observed previously
      appear not to influence the overall error rate of these mutants. However, a
      qualitative analysis of the mutations induced revealed significant differences in
      the mutational spectra between the wild-type and mutant enzymes.

PMID- 9557712
TI  - Epithelial uptake and transport of cell-free human immunodeficiency virus type 1
      and gp120-coated microparticles.
AB  - Cell-free human immunodeficiency virus type 1 (HIV-1) can be taken up and
      released by a monolayer of primary human gingival cells and remain infectious for
      CD4+ cells. Virus-sized latex particles covalently coated with purified native
      HIV-1 envelope glycoprotein gp120 are also transported through the primary
      epithelial cells. This process is significantly stimulated by increasing the
      intracellular cyclic AMP (cAMP) concentration. Inhibition experiments with mannan
      and alpha-methyl-mannopyranoside indicated that mannosyl groups are involved in
      the interaction between gp120 and gingival cells. An increase of cellular
      oligomannosyl receptors by incubation with the mannosidase inhibitor
      deoxymannojirimycin augmented transcellular transport of the gp120-coated
      particles. The results suggest that infectious HIV can penetrate gingival
      epithelia by a cAMP-dependent transport mechanism involving interaction of the
      lectin-like domain of gp120 and mannosyl residues on glycoproteins on the mucosal
      surface. Penetration of HIV could be inhibited by soluble glycoconjugates present
      in oral mucins.

PMID- 9557713
TI  - Detection of a novel bovine lymphotropic herpesvirus.
AB  - Degenerate PCR primers which amplify a conserved region of the DNA polymerase
      genes of the herpesvirus family were used to provide sequence evidence for a new
      bovine herpesvirus in bovine B-lymphoma cells and peripheral blood mononuclear
      cells (PBMC). The sequence of the resultant amplicon was found to be distinct
      from those of known herpesvirus isolates. Alignment of amino acid sequences
      demonstrated 70% identity with ovine herpesvirus 2, 69% with alcelaphine
      herpesvirus 1, 65% with bovine herpesvirus 4, and 42% with bovine herpesvirus 1.
      Phylogenetic analysis placed this putative virus within the tumorigenic
      Gammaherpesvirinae subfamily, and it is tentatively identified as bovine
      lymphotropic herpesvirus. This novel agent was expressed in vitro from infected
      PBMC, and cell-free supernatants were used to transfer infection to a bovine B
      cell line, BL3. Analysis, with specific PCR primers, of DNA from bovine PBMC and
      lymphoma cells identified infection in blood of 91% of adult animals (n = 101),
      63% of lymphomas (n = 32), and 38% of juveniles (n = 13). Of the adults,
      herpesvirus infection was present in 94% of animals that were seropositive for
      bovine leukemia virus (BLV) (n = 63) and in 87% of BLV-seronegative animals (n =
      38). Of the seropositive group, 17 animals exhibited persistent lymphocytosis,
      and 100% of these were herpesvirus positive by PCR. A role for bovine
      lymphotropic herpesvirus as a cofactor in BLV pathogenesis is considered.

PMID- 9557714
TI  - Chemokine receptor utilization by human immunodeficiency virus type 1 isolates
      that replicate in microglia.
AB  - The role of human immunodeficiency virus (HIV) strain variability remains a key
      unanswered question in HIV dementia, a condition affecting around 20% of infected
      individuals. Several groups have shown that viruses within the central nervous
      system (CNS) of infected patients constitute an independently evolving subset of
      HIV strains. A potential explanation for the replication and sequestration of
      viruses within the CNS is the preferential use of certain chemokine receptors
      present in microglia. To determine the role of specific chemokine coreceptors in
      infection of adult microglial cells, we obtained a small panel of HIV type 1
      brain isolates, as well as other HIV strains that replicate well in cultured
      microglial cells. These viruses and molecular clones of their envelopes were used
      in infections, in cell-to-cell fusion assays, and in the construction of
      pseudotypes. The results demonstrate the predominant use of CCR5, at least among
      the major coreceptors, with minor use of CCR3 and CXCR4 by some of the isolates
      or their envelope clones.

PMID- 9557715
TI  - A virus with a mutation in the ICP4-binding site in the L/ST promoter of herpes
      simplex virus type 1, but not a virus with a mutation in open reading frame P,
      exhibits cell-type-specific expression of gamma(1)34.5 transcripts and latency
      associated transcripts.
AB  - The herpes simplex virus type 1 L/S junction-spanning transcripts (L/STs) are a
      family of multisized transcripts expressed at high levels in cells infected with
      mutant viruses that (i) do not express ICP4, (ii) specify forms of ICP4 unable to
      bind to the consensus ICP4 binding site, or (iii) contain mutations in the ICP4
      binding site located at the transcriptional start site of the L/STs. By
      extension, the failure to detect the L/STs in wild-type virus-infected cells is
      due to the repressive effect of ICP4 bound to its cognate binding site upstream
      of the L/ST transcription initiation site. ORF-P, the first and largest open
      reading frame (ORF) encoded by the L/STs, overlaps >90% of the ORF encoding ORF
      34.5, a putative neurovirulence factor, which is transcribed from the opposite
      DNA strand. Viruses with mutations in the overlapping region of ORF-P and ICP34.5
      exhibit premature shutoff of infected-cell protein synthesis and are highly
      attenuated following intracranial inoculation of juvenile mice. To determine
      whether the premature protein shutoff and neuroattenuated phenotypes of ORF-P ORF
      34.5 double mutants are a consequence of alterations in ORF-P, ORF-34.5, or both,
      viruses containing mutations only in ORF-P or only in the ICP4 binding site in
      the L/ST promoter were isolated and characterized. Mutant virus L/ST-n38 contains
      a single-base-pair transition mutation in ORF-P codon 38, resulting in
      translational termination of the ORF-P protein (OPP). This mutation does not
      alter the amino acid sequence of ICP34.5. Expression of a truncated form of OPP
      by mutant virus L/ST-n38 did not result in premature shutoff of infected-cell
      protein synthesis and produced no other observable phenotype relative to wild
      type virus in in vitro tests. Moreover, the 50% lethal dose (LD50) of L/ST-n38
      was comparable to that of wild-type virus following intracranial inoculation of 3
      week-old mice, as were the latency and reactivation phenotypes of the virus.
      These properties of L/ST-n38 indicate that the attenuated phenotype of ORF-P ORF
      34.5 double mutants is a consequence of mutations that affect the function of
      ICP34.5 and not the function of OPP. Mutant virus LST-4BS contains four single
      base-pair substitutions in the ICP4 binding site in the L/ST promoter that
      abrogate the binding of ICP4 to this site, leading to high-level expression of
      the L/STs and OPP. LST-4BS induced premature shutoff of viral and cellular
      protein synthesis and was slightly growth restricted in cells of neural lineage
      (SK-N-SH human neuroblastoma cells) but was wild type for these two parameters in
      cells of nonneural lineage (immortalized primate Vero cells). Of particular
      interest was the observation that L/ST-4BS exhibited cell-type-specific
      expression of both the gamma(1)34.5 transcripts and the latency-associated
      transcripts (LATs). Thus, expression of these transcripts was barely detectable
      in cells of neural lineage (NB41A3 mouse neuroblastoma cells) but was wild type
      in Vero cells. In vivo, L/ST-4BS was reactivated from mouse trigeminal ganglia
      with reduced efficiency and delayed kinetics relative to wild-type virus. L/ST
      4BS was completely attenuated for neurovirulence (LD50 > 10(6) PFU) relative to
      wild-type virus (LD50 < 900 PFU), although the four single-base-pair
      substitutions lie outside the coding region for the neurovirulence factor,
      ICP34.5. Collectively, the complex in vitro and in vivo phenotypes of L/ST-4BS
      can be attributed to (i) disruptions of the ICP4 binding site in the L/ST
      promoter and subsequent overexpression of the L/STs and OPP; (ii) alterations in
      ORF-O, which is also mutated in L/ST-4BS; or (iii) alterations in other cryptic
      genes or cis-acting elements.

PMID- 9557716
TI  - Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine
      treatment for prevention of persistent simian immunodeficiency virus SIVmne
      infection depends critically on timing of initiation and duration of treatment.
AB  - (R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA), an acyclic nucleoside
      phosphonate analog, is one of a new class of potent antiretroviral agents.
      Previously, we showed that PMPA treatment for 28 days prevented establishment of
      persistent simian immunodeficiency virus (SIV) infection in macaques even when
      therapy was initiated 24 h after intravenous virus inoculation. In the present
      study, we tested regimens involving different intervals between intravenous
      inoculation with SIV and initiation of PMPA treatment, as well as different
      durations of treatment, for the ability to prevent establishment of persistent
      infection. Twenty-four cynomolgus macaques (Macaca fascicularis) were studied for
      46 weeks after inoculation with SIV. All mock-treated control macaques showed
      evidence of productive infection within 2 weeks postinoculation (p.i.). All
      macaques that were treated with PMPA for 28 days beginning 24 h p.i. showed no
      evidence of viral replication following discontinuation of PMPA treatment.
      However, extending the time to initiation of treatment from 24 to 48 or 72 h p.i.
      or decreasing the duration of treatment reduced effectiveness in preventing
      establishment of persistent infection. Only half of the macaques treated for 10
      days, and none of those treated for 3 days, were completely protected when
      treatment was initiated at 24 h. Despite the reduced efficacy of delayed and
      shortened treatment, all PMPA-treated macaques that were not protected showed
      delays in the onset of cell-associated and plasma viremia and antibody responses
      compared with mock controls. These results clearly show that both the time
      between virus exposure and initiation of PMPA treatment as well as the duration
      of treatment are crucial factors for prevention of acute SIV infection in the
      macaque model.

PMID- 9557717
TI  - A role for the Sendai virus P protein trimer in RNA synthesis.
AB  - The SeV P protein is found as a homotrimer (P3) when it is expressed in mammalian
      cells, and trimerization is mediated by a predicted coiled-coil motif which maps
      within amino acids (aa) 344 to 411 (the BoxA region). The bacterially expressed
      protein also appears to be trimeric, apparently precluding a role for
      phosphorylation in the association of the P monomers. I have examined the role of
      P trimerization both in the protein's interaction with the nucleocapsid (N:RNA)
      template and in the protein's function on the template during RNA synthesis. As
      with the results of earlier experiments (32), I found that both the BoxA and BoxC
      (aa 479 to 568) regions were required for stable binding of P to the N:RNA.
      Binding was also observed with P proteins containing less than three BoxC
      regions, suggesting that trimerization may be required to permit contacts between
      multiple BoxC regions and the N:RNA. However, these heterologous trimers failed
      to function in viral RNA synthesis, indicating that the third C-terminal leg of
      the trimer plays an essential role in P function on the template. We speculate
      that this function may involve the movement of P (and possibly the polymerase
      complex) on the template and the maintenance of processivity.

PMID- 9557718
TI  - fus-1, a pH shift mutant of Semliki Forest virus, acts by altering spike subunit
      interactions via a mutation in the E2 subunit.
AB  - Semliki Forest virus (SFV), an enveloped alphavirus, is a well-characterized
      paradigm for viruses that infect cells via endocytic uptake and low-pH-triggered
      fusion. The SFV spike protein is composed of a dimer of E1 and E2 transmembrane
      subunits, which dissociate upon exposure to low pH, liberating E2 and the
      fusogenic E1 subunit to undergo independent conformational changes. SFV fusion
      and infection are blocked by agents such as ammonium chloride, which act by
      raising the pH in the endosome and inhibiting the low-pH-induced conformational
      changes in the SFV spike protein. We have previously isolated an SFV mutant, fus
      1, that requires more acidic pH to trigger its fusion activity and is therefore
      more sensitive to inhibition by ammonium chloride. The acid shift in the fusion
      activity of fus-1 was here shown to be due to a more acidic pH threshold for the
      initial dissociation of the fus-1 spike dimer, thereby resulting in a more acidic
      pH requirement for the subsequent conformational changes in both fus-1 E1 and fus
      1 E2. Sequence analysis demonstrated that the fus-1 phenotype was due to a
      mutation in the E2 spike subunit, threonine 12 to isoleucine. fus-1 revertants
      that have regained the parental fusion phenotype and ammonium chloride
      sensitivity were shown to have also regained E2 threonine 12. Our results
      identify a region of the SFV E2 spike protein subunit that regulates the pH
      dependence of E1-catalyzed fusion by controlling the dissociation of the E1/E2
      dimer.

PMID- 9557719
TI  - Evolution of hepatitis C virus quasispecies in hypervariable region 1 and the
      putative interferon sensitivity-determining region during interferon therapy and
      natural infection.
AB  - To study hepatitis C virus (HCV) genetic mutation during interferon (IFN)
      therapy, the temporal changes in HCV quasispecies heterogeneity were compared
      before and after treatment for nine patients infected with HCV genotype 1,
      including four nonresponders, four responders who relapsed after therapy, and one
      responder who experienced a breakthrough of viremia during therapy. Nine
      untreated patients with an average time between specimens of 8.4 years served as
      controls. Sequences from the second envelope glycoprotein gene hypervariable
      region 1 (HVR1) and the putative IFN sensitivity-determining region (ISDR) of the
      nonstructural NS5A gene were analyzed by heteroduplex mobility assays and
      nucleotide sequencing. A strong positive correlation was found between the
      percent change in a heteroduplex mobility ratio (HMR) and percent change in
      nucleotide sequence (r = 0.941, P < 0.001). The rate of fixation of mutations in
      the HVR1 was significantly higher for IFN-treated patients than for controls
      (6.97 versus 1.31% change in HMR/year; P = 0.02). Similarly, a higher rate of
      fixation of mutations was observed in the ISDR for IFN-treated patients than for
      untreated controls, although the result was not significant (1.45 versus 0.15
      amino acid changes/year; P = 0.12). On an individual patient basis, IFN therapy
      was associated with measurable HVR1 and ISDR mutation in nine of nine (100%) and
      two of nine (22.2%) patients, respectively. Evolution to IFN-resistant ISDR
      sequences was observed in only one of nine IFN-treated patients. These data
      suggest that IFN therapy frequently exerts pressure on the HCV envelope region,
      while pressure on the ISDR was evident in only a subset of patients. Thus, the
      selection pressures evoked on HCV genotype 1 quasispecies during IFN therapy
      appear to differ among different patients.

PMID- 9557720
TI  - A chimeric Ty3/Moloney murine leukemia virus integrase protein is active in vivo.
AB  - This report describes the results of experiments to determine whether chimeras
      between a retrovirus and portions of Ty3 are active in vivo. A chimera between
      Ty3 and a Neo(r)-marked Moloney murine leukemia virus (M-MuLV) was constructed.
      The C-terminal domain of M-MuLV integrase (IN) was replaced with the C-terminal
      domain of Ty3 IN. The chimeric retroviruses were expressed from an amphotrophic
      envelope packaging cell line. The virus generated was used to infect the human
      fibrosarcoma cell line HT1080, and cells in which integration had occurred were
      selected by G418 resistance. Three independently integrated viruses were rescued.
      In each case, the C-terminal Ty3 IN sequences were maintained and short direct
      repeats of the genomic DNA flanked the integration site. Sequence analysis of the
      genomic DNA flanking the insertion did not identify a tRNA gene; therefore, these
      integration events did not have Ty3 position specificity. This study showed that
      IN sequences from the yeast retrovirus-like element Ty3 can substitute for M-MuLV
      IN sequences in the C-terminal domain and contribute to IN function in vivo. It
      is also one of the first in vivo demonstrations of activity of a retrovirus
      encoding an integrase chimera. Studies of chimeras between IN species with
      distinctive integration patterns should complement previous work by expanding our
      understanding of the roles of nonconserved domains.

PMID- 9557721
TI  - gag, vif, and nef genes contribute to the homologous viral interference induced
      by a nonproducer human immunodeficiency virus type 1 (HIV-1) variant:
      identification of novel HIV-1-inhibiting viral protein mutants.
AB  - We previously demonstrated that expression of the nonproducer F12-human
      immunodeficiency virus type 1 (HIV-1) variant induces a block in the replication
      of superinfecting HIV that does not depend on the down-regulation of CD4 HIV
      receptors. In order to individuate the gene(s) involved in F12-HIV-induced
      interference, vectors expressing each of the nine F12-HIV proteins were
      transfected in HIV-susceptible HeLa CD4 cells. Pools of cell clones stably
      producing each viral protein were infected with HIV-1, and virus release was
      measured in terms of reverse transcriptase activity in supernatants. We hereby
      demonstrate that HeLa CD4 cells expressing the F12-HIV gag, vif, or nef gene were
      resistant, to different degrees, to infection with T-cell-line-adapted HIV-1
      strains. Conversely, expression of either the tat, rev, or vpu F12-HIV gene
      increased the rate of HIV release, and no apparent effects on HIV replication
      were observed in cells expressing either the F12-HIV vpr, pol, or env gene. No
      variation of CD4 exposure was detected in any of the uninfected HeLa CD4 pools.
      These data indicate that F12-HIV homologous viral interference is the consequence
      of the synergistic anti-HIV effects of Gag, Vif, and Nef proteins. Retrovirus
      vectors expressing F12-HIV vif or nef allowed us to further establish that the
      expression of each mutated protein (i) inhibits the replication of clinical HIV-1
      isolates as well, (ii) impairs the infectivity of the virus released by cells
      chronically infected with HIV-1, and (iii) limitedly to F12-HIV Vif protein,
      induces HIV resistance in both vif-permissive and vif-nonpermissive cells. The
      levels of action of F12-HIV vif and nef anti-HIV effects were also determined. We
      observed that HIV virions emerging from the first viral cycle on F12-HIV vif
      expressing cells, although released in unaltered amounts, had a strongly reduced
      ability to initiate the retrotranscription process when they reinfected parental
      HeLa CD4 cells. Differently, we observed that expression of F12-HIV Nef protein
      affects the HIV life cycle at the level of viral assembling and/or release. For
      the first time, an inhibitory effect on the HIV life cycle in both acutely and
      chronically infected cells induced by mutated Vif and Nef HIV-1 proteins is
      described. These genes could thus be proposed as new useful reagents for anti-HIV
      gene therapy.

PMID- 9557722
TI  - Deletion analysis of a defective interfering Semliki Forest virus RNA genome
      defines a region in the nsP2 sequence that is required for efficient packaging of
      the genome into virus particles.
AB  - The 1,244-nucleotide genome of Semliki Forest virus (SFV) defective interfering
      (DI) RNA 19 (DI-19) is coterminal with the infectious genome and contains two
      major deletions. One deletion removes the end of the nsP1 gene and the beginning
      of the nsP2 gene, and the other removes the end of the nsP2 gene, the nsP3 and
      nsP4 genes, and all of the structural protein genes (M. Thomson and N. J.
      Dimmock, Virology 199:354-365, 1994). Like all DI SFV RNAs, DI-19 contains three
      regions that are conserved. Region a comprises the 5' terminus continuous with
      part of the nsP1 gene, region b comprises a central part of the nsP2 gene, and
      region c comprises the 3' terminus and the associated untranslated region. A
      deletion analysis of the 265-nucleotide b region (nucleotides 679 to 943,
      inclusive) was undertaken to determine its role in genome replication and
      packaging into DI virus particles. Deleted plasmids were constructed and
      transcribed, and the resulting DI RNAs were transfected into SFV-infected BHK
      cells. Putative progeny DI virus particles that had been released into the tissue
      culture fluid were then serially passaged in new monolayers together with added
      high-multiplicity SFV, and cells and tissue culture fluids were tested for the
      presence of DI RNA by reverse transcription-PCR. DI RNA that had all of the b
      region deleted was replicated well in BHK-21 cells, as shown by the presence of
      large amounts of negative-sense DI RNA and an increase in the amount of positive
      sense RNA in the cytoplasm, but was packaged very inefficiently, as indicated by
      very low amounts of DI RNA in the tissue culture fluid. The genome of a deletion
      mutant that retained the 3' 224 nucleotides of region b was packaged
      successfully, but one that retained only the 5' 41 nucleotides was not detected
      in the tissue culture fluid. These and other data suggest that nucleotides 720 to
      777 of region b are of particular importance in the packaging process. This
      finding agrees with data obtained with Ross River virus and contrasts with the
      well-studied Sindbis alphavirus major packaging signal that is located within the
      nsP1 gene.

PMID- 9557723
TI  - African origin of human T-lymphotropic virus type 2 (HTLV-2) supported by a
      potential new HTLV-2d subtype in Congolese Bambuti Efe Pygmies.
AB  - We identified a potential new subtype within human T-cell lymphotropic virus type
      2 (HTLV-2), HTLV-2d, present in members of an isolated Efe Bambuti Pygmy tribe.
      Two of 23 Efe Pygmies were HTLV-2 seropositive, with HTLV-2 Western blot and
      enzyme-linked immunosorbent assay reactivities. From one of them the entire
      genome of the HTLV-2 strain Efe2 could be amplified and sequenced. In all gene
      regions analyzed, this strain was the most divergent HTLV-2 strain, differing by
      2.4% (tax/rex) to 10.7% (long terminal repeat) from both subtypes HTLV-2a and
      HTLV-2b, yet major functional elements are conserved. The similarity between the
      HTLV-2 Efe2 Gag and Env proteins and the corresponding HTLV-2a and -2b proteins
      is consistent with the observed serological reactivity. In the proximal pX
      region, one of the two alternative splice acceptor sites is abolished in HTLV-2
      Efe2. Another interesting feature of this potential new subtype is that it has a
      Tax protein of 344 amino acids (aa), which is intermediate in length between the
      HTLV-2a Tax protein (331 aa) and the HTLV-2b and -2c Tax proteins (356 aa) and
      similar to the simian T-cell lymphotropic virus type 2 (STLV-2) PP1664 Tax
      protein. Together these two findings suggest a different phenotype for the HTLV-2
      Efe2 strain. Phylogenetic analyses confirmed that the Pygmy Efe2 strain
      potentially belonged to a new and quite divergent subtype, HTLV-2d. When the STLV
      2 bonobo viruses PP1664 and PanP were used as an outgroup, it was clear that the
      Pygmy HTLV-2 Efe2 strain had the longest independent evolution and that HTLV-2
      evolution is consistent with an African origin.

PMID- 9557724
TI  - A 68-nucleotide sequence within the 3' noncoding region of simian hemorrhagic
      fever virus negative-strand RNA binds to four MA104 cell proteins.
AB  - The 3' noncoding region (NCR) of the negative-strand RNA [3'(-)NCR RNA] of the
      arterivirus simian hemorrhagic fever virus (SHFV) is 209 nucleotides (nt) in
      length. Since this 3' region, designated 3'(-)209, is the site of initiation of
      full-length positive-strand RNA and is the template for the synthesis of the 5'
      leader sequence, which is found on both full-length and subgenomic mRNAs, it is
      likely to contain cis-acting signals for RNA synthesis and to interact with
      cellular and viral proteins to form replication complexes. Gel mobility shift
      assays showed that cellular proteins in MA104 S100 cytoplasmic extracts formed
      two complexes with the SHFV 3'(-)209 RNA, and results from competition gel
      mobility shift assays demonstrated that these interactions were specific. Four
      proteins with molecular masses of 103, 86, 55, and 36 kDa were detected in UV
      induced cross-linking assays, and three of these proteins (103, 55, and 36 kDa)
      were also detected by Northwestern blotting assays. Identical gel mobility shift
      and UV-induced cross-linking patterns were obtained with uninfected and SHFV
      infected extracts, indicating that the four proteins detected are cellular, not
      viral, proteins. The binding sites for the four cellular proteins were mapped to
      the region between nt 117 and 184 (68-nt sequence) from the 3' end of the SHFV
      negative-strand RNA. This 68-nt sequence was predicted to form two stem-loops,
      SL4 and SL5. The 3'(-)NCR RNA of another arterivirus, lactate dehydrogenase
      elevating virus C (LDV-C), competed with the SHFV 3'(-)209 RNA in competition gel
      mobility shift assays. UV-induced cross-linking assays showed that four MA104
      cellular proteins with the same molecular masses as those that bind to the SHFV
      3'(-)209 RNA also bind to the LDV-C 3'(-)NCR RNA and equine arteritis virus 3'(
      )NCR RNA. However, each of these viral RNAs also bound to an additional MA104
      protein. The binding sites for the MA104 cellular proteins were shown to be
      located in similar positions in the LDV-C 3'(-)NCR and SHFV 3'(-)209 RNAs. These
      data suggest that the binding sites for a set of the cellular proteins are
      conserved in all arterivirus RNAs and that these cell proteins may be utilized as
      components of viral replication complexes.

PMID- 9557726
TI  - Gene expression and regulation from the p7 promoter of Aedes densonucleosis
      virus.
AB  - The nonstructural proteins NS1 and NS2 are thought to be expressed from the p7
      promoter of Aedes densonucleosis virus (AeDNV). To study gene expression from the
      p7 promoter, eight different plasmids were constructed by fusing beta
      galactosidase or beta-glucuronidase into the genome so that the reporter gene was
      in different open reading frames and under the transcriptional control of the p7
      promoter. After transfection into C6/36 Aedes albopictus cells, constructs
      generated comparable amounts of RNA, but only the NS1 and NS2 fusion constructs
      produced appreciable levels of active enzyme. NS1 and NS2 fusion constructs
      contained wild-type AeDNV sequences from the p7 promoter downstream to nucleotide
      458. The remaining constructs, with the exception of p7GUS.rf3, lacked some or
      all of these necessary sequences and inefficiently produced protein. These data
      suggest that sequences downstream of the p7 promoter play a role in translational
      regulation of gene expression from the p7 promoter of AeDNV.

PMID- 9557725
TI  - Epidemiology of infection with Epstein-Barr virus types 1 and 2: lessons from the
      study of a T-cell-immunocompromised hemophilic cohort.
AB  - In apparent contrast to earlier work on Epstein-Barr virus (EBV) carriage in the
      general Caucasian population, in vitro virus isolations from human
      immunodeficiency virus (HIV)-positive male homosexual cohorts have shown frequent
      examples of multiple EBV infection and an overall prevalence of type 2 EBV
      strains exceeding 30%. Here we ask to what extent these findings might hold true
      in another T-cell-immunocompromised cohort, HIV-positive hemophilic patients.
      Resident EBV strains were rescued within lymphoblastoid cell lines derived from
      the blood and throat washings of 39 such individuals, using the same in vitro
      protocols of virus isolation as for the homosexual cohort. A mean of 19
      independent cell lines was made per patient, and in each case the resident virus
      was characterized by PCR-based viral genomic analysis and by immunoblotting to
      reveal the viral "EBNAprint." By these criteria a significant proportion (14 of
      39) of the hemophilic cohort carried more than one EBV strain, suggesting that T
      cell impairment does indeed sensitize virus carriers to reinfection with new
      strains of exogenously transmitted virus. However, the overall incidence of type
      2 EBV infection was 10%, which is close to that observed in the earlier work with
      healthy carriers and substantially lower than that seen in HIV-positive
      homosexuals. We infer that type 2 EBV is relatively rare in the general Caucasian
      population but has become endemic in the homosexual community.

PMID- 9557727
TI  - Cell-to-cell contact as an efficient mode of Epstein-Barr virus infection of
      diverse human epithelial cells.
AB  - We show clear evidence for direct infection of various human epithelial cells by
      Epstein-Barr virus (EBV) in vitro. The successful infection was achieved by using
      recombinant EBV (Akata strain) carrying a selective marker gene but without any
      other artificial operations, such as introduction of the known EBV receptor
      (CD21) gene or addition of polymeric immunoglobulin A against viral gp350 in
      culture. Of 21 human epithelial cell lines examined, 18 became infected by EBV,
      as ascertained by the detection of EBV-determined nuclear antigen (EBNA) 1
      expression in the early period after virus exposure, and the following selection
      culture easily yielded a number of EBV-infected clones from 15 cell lines. None
      of the human fibroblasts and five nonhuman-derived cell lines examined was
      susceptible to the infection. By comparison, cocultivation with virus producers
      showed approximately 800-fold-higher efficiency of infection than cell-free
      infection did, suggesting the significance of direct cell-to-cell contact as a
      mode of virus spread in vivo. Most of the epithelial cell lines infectable with
      EBV were negative for CD21 expression at the protein and mRNA levels. The
      majority of EBV-infected clones established from each cell line invariably
      expressed EBNA1, EBV-encoded small RNAs, rightward transcripts from the BamHI-A
      region of the virus genome, and latent membrane protein (LMP) 2A, but not the
      other EBNAs or LMP1. This restricted form of latent viral gene expression, which
      is a central issue for understanding epithelial oncogenesis by EBV, resembled
      that seen in EBV-associated gastric carcinoma and LMP1-negative nasopharyngeal
      carcinoma. The results indicate that direct infection of epithelial cells by EBV
      may occur naturally in vivo, and this could be mediated by an unidentified,
      epithelium-specific binding receptor for EBV. The EBV convertants are viewed, at
      least in terms of viral gene expression, as in vitro analogs of EBV-associated
      epithelial tumor cells, thus facilitating analysis of an oncogenic role(s) for
      EBV in epithelial cells.

PMID- 9557728
TI  - Borna disease virus-induced neurological disorder in mice: infection of neonates
      results in immunopathology.
AB  - Borna disease virus (BDV) is a neurotropic nonsegmented negative-stranded RNA
      virus that persistently infects warm-blooded animals. In horses and other natural
      animal hosts, infections with BDV cause meningoencephalitis and behavioral
      disturbances. Experimental infection of adult mice takes a nonsymptomatic course,
      an observation previously believed to indicate that this animal species is not
      suitable for pathogenesis studies. We now demonstrate that BDV frequently induces
      severe neurological disease in infected newborn mice. Signs of neurological
      disease were first observed 4 to 6 weeks after intracerebral infection. They
      included a characteristic nonphysiological position of the hind limbs at an early
      stage of the disease and paraparesis at a later stage. Histological examination
      revealed large numbers of perivascular and meningeal inflammatory cells in brains
      of diseased mice and, unexpectedly, no increase in immunoreactivity to glial
      fibrillar acidic protein. The incidence and severity of BDV-induced disease
      varied dramatically among mouse strains. While only 13% of the infected C57BL/6
      mice showed disease symptoms, which were mostly transient, more than 80% of the
      infected MRL mice developed severe neurological disorder. In spite of these
      differences in susceptibility to disease, BDV replicated to comparable levels in
      the brains of mice of the various strains used. Intracerebral infections of
      newborn beta2-microglobulin-deficient C57BL/6 and MRL mice, which both lack CD8+
      T cells, did not result in meningoencephalitis or neurological disease,
      indicating that the BDV-induced neurological disorder in mice is a cytotoxic T
      cell-mediated immunopathological process. With this new animal model it should
      now be possible to characterize the disease-inducing immune response to BDV in
      more detail.

PMID- 9557729
TI  - Virus-specific CD4+ T cells eliminate borna disease virus from the brain via
      induction of cytotoxic CD8+ T cells.
AB  - Persistent Borna disease virus infection of the brain can be prevented by
      treatment of naive rats with a virus-specific CD4+ T-cell line prior to
      infection. In rats receiving this treatment, only a transient low-level
      encephalitis was seen compared to an increasingly inflammatory reaction in
      untreated infected control rats. Virus replication was found in the brain for
      several days after infection before the virus was cleared from the central
      nervous system. The loss of infectivity from the brain was confirmed by negative
      results by reverse transcription-PCR with primers for mRNA, by in situ
      hybridization for both genomic and mRNA, and by immunohistology. Most
      importantly, in vitro assays revealed that the T-cell line used for transfusion
      had no cytotoxic capacity. The kinetics of virus clearance were paralleled by the
      appearance of CD8+ T cells and the expression of perforin in the brain. Testing
      of lymphocytes isolated from the brains of CD4+ T-cell-treated rats after
      challenge revealed high cytotoxic activity due to the presence of CD8+ cytotoxic
      T cells at time points when brain lymphocytes from infected control rats induced
      low-level cytolysis of target cells. Neutralizing antiviral antibodies and gamma
      interferon were shown not to be involved in the elimination of virus from the
      brain.

PMID- 9557730
TI  - Structure of a neutralizing antibody bound monovalently to human rhinovirus 2.
AB  - The structure of a complex between human rhinovirus 2 (HRV2) and the Fab fragment
      of neutralizing monoclonal antibody (MAb) 3B10 has been determined to 25-A
      resolution by cryoelectron microscopy and three-dimensional reconstruction
      techniques. The footprint of 3B10 on HRV2 is very similar to that of neutralizing
      MAb 8F5, which binds bivalently across the icosahedral twofold axis. However, the
      3B10 Fab fragment (Fab-3B10) is bound in an orientation, inclined at
      approximately 45 degrees to the surface of the virus capsid, which is compatible
      only with monovalent binding of the antibody. The canyon around the fivefold axis
      is not directly obstructed by the bound Fab. The X-ray structures of a closely
      related HRV (HRV1A) and a Fab fragment were fitted to the density maps of the
      HRV2-Fab-3B10 complex obtained by cryoelectron microscope techniques. The
      footprint of 3B10 on the viral surface is largely on VP2 but also covers the VP3
      loop centered on residue 3064 and the VP1 loop centered on residue 1267. MAb 3B10
      can interact directly with VP2 residue 2164, the site of an escape mutation on
      VP2, and with VP1 residues 1264 to 1267, the site of a deletion escape mutation.
      Deletion of these residues shortens the VP1 loop, moving it away from the MAb
      binding site. All structural and biochemical evidence indicates that MAb 3B10
      binds to a conformation epitope on HRV2.

PMID- 9557731
TI  - Cryoelectron microscopic examination of human immunodeficiency virus type 1
      virions with mutations in the cyclophilin A binding loop.
AB  - The human immunodeficiency virus type 1 capsid protein contains a conserved
      P217X4PX2PX5P231 motif. Mutation at Pro-222 decreases virion incorporation of
      cyclophilin A, while mutation at Pro-231 abolishes infectivity. Although viral
      RNA incorporation and protease cleavage of the Gag precursor were not affected by
      these mutations, cryoelectron microscopy revealed a loss of virion maturation in
      P231A particles.

PMID- 9557732
TI  - Human and simian T-cell leukemia viruses type 2 (HTLV-2 and STLV-2(pan-p))
      transform T cells independently of Jak/STAT activation.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 differ in pathogenicity in
      vivo. HTLV-1 causes leukemia and neurologic and inflammatory diseases, whereas
      HTLV-2 is less clearly associated with human disease. Both retroviruses transform
      human T cells in vitro, and transformation by HTLV-1 was found to be associated
      with the constitutive activation of the Jak/STAT pathway. To assess whether HTLV
      2 transformation may also result in constitutive activation of the Jak/STAT
      pathway, six interleukin-2-independent, HTLV-2-transformed T-cell lines were
      analyzed for the presence of activated Jak and STAT proteins by electrophoretic
      mobility shift assay. In addition, the phosphorylation status of Jak and STAT
      proteins was assessed directly by immunoprecipitation and immunoblotting with an
      antiphosphotyrosine antibody. Jak/STAT proteins were not found to be
      constitutively activated in any of the T-cell lines infected by the type 2 human
      and nonhuman primate viruses, suggesting that HTLV-2 and the cognate virus simian
      T-lymphotropic virus type 2 from Pan paniscus transform T cells in vitro by
      mechanisms at least partially different from those used by HTLV-1.

PMID- 9557733
TI  - Bovine leukemia virus-induced lymphocytosis and increased cell survival mainly
      involve the CD11b+ B-lymphocyte subset in sheep.
AB  - In this study, we show that bovine leukemia virus (BLV)-induced persistent
      lymphocytosis (PL) results from the in vivo expansion of the CD11b+ B-lymphocyte
      population. This subset shares phenotypic characteristics with murine and human B
      1 cells. BLV interactions with the sheep B-1-like subset were explored. We found
      that B-1- and B-2-like cells are initially infected to similar extents. However,
      in long-term-infected sheep, the viral load is higher in B-1-like cells and only
      B-1- and not B-2-like cells show increased ex vivo survival compared to that in
      uninfected sheep. Ex vivo viral expression was found in both B-1- and B-2-like
      cells, indicating that both cell types support viral replication. Finally,
      cycloheximide and a protein kinase C inhibitor (H7) that blocks the ex vivo
      activation of viral expression did not affect the increased survival in B-1-like
      cells, suggesting that resistance to apoptosis is acquired in vivo. Collectively,
      these results indicate a peculiar susceptibility of sheep B-1-like cells to BLV
      transforming effects and further support the involvement of increased survival in
      BLV pathogenesis.

PMID- 9557734
TI  - Biological characterization of Rev variation in equine infectious anemia virus.
AB  - Sequence analysis identified significant variation in the second exon of equine
      infectious anemia virus (EIAV) rev. Functional analysis indicated that limited
      amino acid variation in Rev significantly altered the export activity of the
      protein but did not affect Rev-dependent alternative splicing. EIAV Rev can
      mediate export through two independent cis-acting Rev-responsive elements (RREs),
      and differences among Rev variants were more pronounced when both RREs were
      present. Variation in Rev may be an important mechanism for regulation of virus
      replication in vivo and may contribute to changes in clinical disease.

PMID- 9557735
TI  - Functions of conserved motifs in the RNA-dependent RNA polymerase of a yeast
      double-stranded RNA virus.
AB  - At least eight conserved motifs are visible in the totivirus RNA-dependent RNA
      polymerase (RDRP). We have systematically altered each of these in the
      Saccharomyces cerevisiae double-stranded RNA virus ScVL1 by substituting the
      conserved motifs from a giardiavirus. The results help define the conserved
      regions of the RDRP involved in polymerase function and those essential for other
      reasons.

PMID- 9557736
TI  - Herpes simplex virus 2 UL45 is a type II membrane protein.
AB  - In addition to eleven glycoproteins, the herpes simplex virus type 2 (HSV-2)
      genome encodes several proteins with potential membrane-spanning segments but no
      asparagine-linked carbohydrates. One of these is UL45. Fractionation of infected
      cells showed that HSV-2 UL45 is an integral membrane protein, and analysis of
      UL45 mutants with potential glycosylation sites showed that it has a type II
      membrane orientation, the first HSV protein known to have this orientation.
      Furthermore, it is detectable in infected cells at a time similar to that when
      glycoproteins gB and gD are detected, consistent with a role in cell-cell fusion,
      which has previously been found for HSV-1 UL45.

PMID- 9557737
TI  - Different patterns of neuronal infection after intracerebral injection of two
      strains of pseudorabies virus.
AB  - Pseudorabies virus (PRV), a swine neurotropic alphaherpesvirus, is known to
      invade the central nervous system (CNS) of a variety of animal species through
      peripherally projecting axons, replicate in the parent neurons, and then pass
      transsynaptically to infect other neurons of a circuit. Studies of the human
      pathogen herpes simplex virus type 1 have reported differences in the direction
      of transport of two strains of this virus after direct injection into the primate
      motor cortex. In the present study we examined the direction of transport of
      virulent and attenuated strains of PRV, utilizing injections into the rat
      prefrontal cortex to evaluate specific movement of virus through CNS circuitry.
      The data demonstrate strain-dependent patterns of infection consistent with
      bidirectional (anterograde and retrograde) transport of virulent virus and
      unidirectional (retrograde) transport of attenuated PRV from the site of
      injection. The distribution of infected neurons and the extent of transsynaptic
      passage also suggest that a release defect in the attenuated strain reduces the
      apparent rate of viral transport through neuronal circuitry. Finally, injection
      of different concentrations of virus influenced the onset of replication within a
      neural circuit. Taken together, these data suggest that viral envelope
      glycoproteins and virus concentration at the site of injection are important
      determinants of the rate and direction of viral transport through a multisynaptic
      circuit in the CNS.

PMID- 9557738
TI  - Role of the N-terminal zinc finger of human immunodeficiency virus type 1
      nucleocapsid protein in virus structure and replication.
AB  - Nucleocapsid protein (NCp7) of human immunodeficiency virus type 1 is found
      covering the genomic RNA in the interior of the viral particle. It is a highly
      basic protein with two zinc fingers of the form CX2CX4HX4C which exhibit strong
      affinity for a zinc cation. To study the structure-function relationship of the N
      terminal zinc finger of NCp7, this domain was either deleted or changed to
      CX2CX4CX4C. We examined virus formation and structure as well as proviral DNA
      synthesis. Our data show that these two NC mutations result in the formation of
      particles with an abnormal core morphology and impair the end of proviral DNA
      synthesis, leading to noninfectious viruses.

PMID- 9557739
TI  - PITALRE, the catalytic subunit of TAK, is required for human immunodeficiency
      virus Tat transactivation in vivo.
AB  - The human cdc2-related kinase PITALRE is the catalytic component of TAK, the Tat
      associated kinase. Previously, we have proposed that TAK is a cellular factor
      that mediates Tat transactivation function. Here we demonstrate that transient
      overexpression of PITALRE specifically squelches Tat-1 activation of both a
      transfected and an integrated human immunodeficiency virus type 1 (HIV-1) long
      terminal repeat (LTR), suggesting that PITALRE mediates Tat function as a
      multiprotein complex. A catalytic mutant of PITALRE, D167N, was found to be more
      efficient than wild-type PITALRE in squelching Tat transactivation. Neither wild
      type PITALRE nor D167N was able to squelch transactivation of the human T-cell
      leukemia type 1 LTR by the Tax protein. Additionally, we show that artificial
      targeting of PITALRE to a nascent RNA element, in the absence of Tat, activated
      HIV-1 LTR expression. These results indicate that a PITALRE-containing complex
      mediates transactivation by Tat and suggest that Tat proteins function by
      localizing such a PITALRE-containing complex to the site of the transcribing
      provirus.

PMID- 9557740
TI  - Antibody response in mice inoculated with DNA expressing foot-and-mouth disease
      virus capsid proteins.
AB  - Candidate foot-and-mouth disease (FMD) DNA vaccines designed to produce viral
      capsids lacking infectious viral nucleic acid were evaluated. Plasmid DNAs
      containing a portion of the FMDV genome coding for the capsid precursor protein
      (P1-2A) and wild-type or mutant viral proteinase 3C (plasmids P12X3C or P12X3C
      mut, respectively) were constructed. Cell-free translation reactions programmed
      with pP12X3C (wild-type 3C) and pP12X3C-mut produced a capsid precursor, but only
      the reactions programmed with the plasmid encoding the functional proteinase
      resulted in P1-2A processing and capsid formation. Baby hamster kidney (BHK)
      cells also produced viral capsid proteins when transfected with these plasmids.
      Plasmid P12X3C was administered to mice by intramuscular, intradermal, and
      epithelial (gene gun) inoculations. Anti-FMD virus (FMDV) antibodies were
      detected by radioimmunoprecipitation (RIP) and plaque reduction neutralization
      assays only in sera of mice inoculated by using a gene gun. When pP12X3C and
      pP12X3C-mut were inoculated into mice by using a gene gun, both plasmids elicited
      an antibody response detectable by RIP but only pP12X3C elicited a neutralizing
      antibody response. These results suggest that capsid formation in situ is
      required for effective immunization. Expression and stimulation of an immune
      response was enhanced by addition of an intron sequence upstream of the coding
      region, while addition of the FMDV internal ribosome entry site or leader
      proteinase (L) coding region either had no effect or reduced the immune response.

PMID- 9557741
TI  - Human T-cell leukemia virus type 1 pX-I and pX-II open reading frames are
      dispensable for the immortalization of primary lymphocytes.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) infects and transforms CD4+ T
      lymphocytes both in vivo and in vitro. Although the Tax protein of HTLV-1 has
      been strongly implicated as a transforming agent, other virally encoded proteins
      may also play a role in the transformation process. In addition to the rex and
      tax genes, the pX region of the HTLV-1 genome contains two open reading frames
      (pX-I and pX-II) which encode the putative viral accessory proteins known as
      p12I, p30II, and p13II. Mutations in the ACH molecular clone of HTLV-1 that are
      predicted to abrogate the expression of p12I, p13II and p30II were constructed.
      These mutations had no effect on viral replication or the immortalization of
      primary lymphocytes. Although these proteins are dispensable for viral
      replication and immortalization in vitro, it remains possible that they alter
      infection in vivo.

PMID- 9557742
TI  - The rubella virus nonstructural protease requires divalent cations for activity
      and functions in trans.
AB  - The rubella virus (RUB) nonstructural (NS) protease is a papain-like cysteine
      protease (PCP) located in the NS-protein open reading frame (NSP-ORF) that
      cleaves the NSP-ORF translation product at a single site to produce two products,
      P150 (the N-terminal product) and P90 (the C-terminal product). The RUB NS
      protease was found not to function following translation in vitro in a standard
      rabbit reticulocyte lysate system, although all of the other viral PCPs do so.
      However, in the presence of divalent cations such as Zn2+, Cd2+, and Co2+, the
      RUB NS protease functioned efficiently, indicating that these cations are
      required either as direct cofactors in catalytic activity or for correct
      acquisition of three-dimensional conformation of the protease. Since other viral
      and cell PCPs do not require cations for activity and the RUB NS protease
      contains a putative zinc binding motif, the latter possibility is more likely.
      Previous in vivo expression studies of the RUB NS protease failed to demonstrate
      trans cleavage activity (J.-P. Chen et al., J. Virol. 70:4707-4713, 1996). To
      study whether trans cleavage could be detected in vitro, a protease catalytic
      site mutant and a mutant in which the C-terminal 31 amino acids of P90 were
      deleted were independently introduced into plasmid constructs that express the
      complete NSP-ORF. Cotranslation of these mutants in vitro yielded both the native
      and the mutated forms of P90, indicating that the protease present in the mutated
      construct cleaved the catalytic-site mutant precursor. Thus, RUB NS protease can
      function in trans.

PMID- 9557743
TI  - Recombinant respiratory syncytial virus (RSV) bearing a set of mutations from
      cold-passaged RSV is attenuated in chimpanzees.
AB  - A set of five missense mutations previously identified by nucleotide sequence
      analysis of subgroup A cold-passaged (cp) respiratory syncytial virus (RSV) has
      been introduced into a recombinant wild-type strain of RSV. This recombinant
      virus, designated rA2cp, appears to replicate less efficiently in the upper and
      lower respiratory tracts of seronegative chimpanzees than either biologically
      derived or recombinant wild-type RSV. Infection with rA2cp also resulted in
      significantly less rhinorrhea and cough than infection with wild-type RSV. These
      findings confirm the role of the cp mutations in attenuation of RSV and identify
      their usefulness for inclusion in future live attenuated recombinant RSV vaccine
      candidates.

PMID- 9557744
TI  - Immunogenicity and protective efficacy in mice of influenza B virus vaccines
      grown in mammalian cells or embryonated chicken eggs.
AB  - The immunogenicity and protective efficacy of formalin-inactivated influenza
      B/Memphis/1/93 virus vaccines propagated exclusively in Vero cells, MDCK cells,
      or embryonated chicken eggs (hereafter referred to as eggs) were investigated.
      Mammalian cell-grown viruses differ from the egg-grown variant at amino acid
      position 198 (Pro/Thr) in the hemagglutinin gene. The level of neuraminidase
      activity was highest in egg-grown virus, while MDCK and Vero cell-derived viruses
      possessed 70 and 90% less activity, respectively. After boosting, each of the
      vaccines induced high levels of hemagglutinin-inhibiting, neuraminidase
      inhibiting, and neutralizing antibodies that provided complete protection from
      MDCK-grown virus challenge. Mammalian cell-derived virus vaccines induced serum
      antibodies that were more cross-reactive, while those induced by egg-grown virus
      vaccines were more specific to the homologous antigen. Enzyme-linked immunospot
      analysis indicated that cell-grown virus vaccines induced high frequencies of
      immunoglobulin G (IgG)-producing cells directed against both cell- and egg-grown
      virus antigens, whereas egg-grown virus vaccine induced higher frequencies of IgG
      and IgM-producing cells reacting with homologous antigen and low levels of IgG
      producing cells reactive with cell-grown viruses. These studies indicate that
      influenza B virus variants selected in different host systems can elicit
      different immune responses, but these alterations had no detectable influence on
      the protective efficacy of the vaccines with the immunization protocol used in
      this study.

PMID- 9557745
TI  - Determinants of entry cofactor utilization and tropism in a dualtropic human
      immunodeficiency virus type 1 primary isolate.
AB  - Human immunodeficiency virus type 1 strain 89.6 is a dualtropic isolate that
      replicates in macrophages and transformed T cells, and its envelope mediates CD4
      dependent fusion and entry with CCR5, CXCR-4, and CCR3. To map determinants of
      cofactor utilization by 89.6 and determine the relationship between cofactor use
      and tropism, we analyzed recombinants generated between 89.6 and T-cell-tropic
      (HXB) or macrophage-tropic (JRFL) strains. These chimeras showed that regions of
      89.6 env outside V3 through V5 determine CXCR-4 utilization and T-cell line
      tropism as well as CCR5 utilization and macrophage tropism. However, the 89.6 env
      V3 domain also conferred on HXB the ability to use CCR5 for fusion and entry but
      not the ability to establish productive macrophage infection. CCR3 use was
      conferred on HXB by 89.6 env V3 or V3 through V5 sequences. While replacement of
      the 89.6 V3 through V5 region with HXB sequences abrogated CCR3 utilization,
      replacement of V3 or V4 through V5 separately did not. Thus, CCR3 use is
      determined by sequences within V3 through V5 and most likely can be conferred by
      either the V3 or the V4 through V5 domains. These results indicate that cofactor
      utilization and tropism in this dualtropic isolate are determined by complex
      interactions among multiple env segments, that distinct regions of the Env
      glycoprotein may be important for utilization of different chemokine receptors,
      and that determinants in addition to cofactor usage participate in postentry
      stages in the virus replication cycle that contribute to target cell tropism.

PMID- 9557746
TI  - Patterns of CCR5, CXCR4, and CCR3 usage by envelope glycoproteins from human
      immunodeficiency virus type 1 primary isolates.
AB  - Coreceptor usage by Envs from diverse primary human immunodeficiency virus type 1
      isolates was analyzed by a vaccinia virus-based expression and assay system.
      Usage of recombinant CCR5 and CXCR4 correlated closely with fusogenicity toward
      macrophages and T-cell lines expressing endogenous coreceptors. Surprisingly,
      recombinant CCR3 was utilized by most primary and T-cell-line-adapted Envs.
      Endogenous CXCR4 in macrophages was functional as a coreceptor.

PMID- 9557747
TI  - Detection of viral proteins after infection of cultured hepatocytes with rabbit
      hemorrhagic disease virus.
AB  - The calicivirus rabbit hemorrhagic disease virus (RHDV), which replicates
      predominantly in the livers of infected rabbits, cannot be propagated in tissue
      culture. To enable the performance of in vitro studies, rabbit hepatocytes were
      isolated by liver perfusion and gradient centrifugation. After inoculation with
      purified RHDV, more than 50% of the cells proved to be infected. Protein analyses
      led to the detection of 13 RHDV-specific polypeptides within the infected cells.
      These proteins were assigned to defined regions of the viral genome, resulting in
      a refined model of RHDV genome organization.

PMID- 9557748
TI  - Respiratory syncytial virus infection of human alveolar epithelial cells enhances
      interferon regulatory factor 1 and interleukin-1beta-converting enzyme gene
      expression but does not cause apoptosis.
AB  - The induction kinetics of the transcriptional activities of interferon regulatory
      factor 1 (IRF-1), interleukin-1beta-converting enzyme (ICE), and CPP32 by
      respiratory syncytial virus (RSV) infection of human type II alveolar epithelial
      cells (A549 cells) were analyzed semiquantitatively by reverse transcriptase PCR.
      The appearance of ICE and CPP32 protein in cell lysate was examined by Western
      blotting analysis. The induction of apoptosis by RSV infection was examined by
      the appearance of DNA fragmentation detected by terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling. RSV
      moderately enhanced IRF-1 mRNA as early as 4 h after infection, and this
      enhancement lasted several hours. Following induction of the IRF-1 gene, ICE gene
      expression increased significantly, and an increase of ICE protein was observed
      in the RSV-infected cell lysate. These increments were observed in cells treated
      with live RSV but not in cells treated with inactivated RSV or control antigen.
      However, no infection-specific increase of CPP32 gene expression or the protein
      was observed. No nucleosomal fragmentation was observed in RSV-infected cells
      during the whole course of infection, despite the appearance of extensive
      cytopathic change and cell death. These observations suggest that RSV infection
      of human alveolar epithelial cells induces the ICE gene and its protein as a
      result of increased IRF-1 induction but that the increased ICE was insufficient
      to cause apoptosis in the RSV-infected cells. ICE might not be able to activate
      CPP32, which is thought to be the more important protease for apoptosis.

PMID- 9557749
TI  - Identification of a full-length cDNA for an endogenous retrovirus of miniature
      swine.
AB  - Endogenous retroviruses of swine are a concern in the use of pig-derived tissues
      for xenotransplantation into humans. The nucleotide sequence of porcine
      endogenous retrovirus taken from lymphocytes of miniature swine (PERV-MSL) has
      been characterized. PERV-MSL is a type C retrovirus of 8,132 bp with the greatest
      nucleic acid sequence identity to gibbon ape leukemia virus and murine leukemia
      virus. Constitutive production of PERV-MSL RNA has been detected in normal
      leukocytes and in multiple organs of swine. The copy numbers of full-length PERV
      sequences per genome (approximately 8 to 15) vary among swine strains. The open
      reading frames for gag, pol, and env in PERV-MSL have over 99% amino acid
      sequence identity to those of Tsukuba-1 retrovirus and are highly homologous to
      those of endogenous retrovirus of cell line PK15 (PK15-ERV). Most of the
      differences in the predicted amino acid sequences of PK15-ERV and PERV-MSL are in
      the SU (cell attachment) region of env. The existence of these PERV clones will
      enable studies of infection by endogenous retroviruses in xenotransplantation.

PMID- 9557750
TI  - Feline coronavirus type II strains 79-1683 and 79-1146 originate from a double
      recombination between feline coronavirus type I and canine coronavirus.
AB  - Recent evidence suggests that the type II feline coronavirus (FCoV) strains 79
      1146 and 79-1683 have arisen from a homologous RNA recombination event between
      FCoV type I and canine coronavirus (CCV). In both cases, the template switch
      apparently took place between the S and M genes, giving rise to recombinant
      viruses which encode a CCV-like S protein and the M, N, 7a, and 7b proteins of
      FCoV type I (K. Motowaka, T. Hohdatsu, H. Hashimoto, and H. Koyama, Microbiol.
      Immunol. 40:425-433, 1996; H. Vennema, A. Poland, K. Floyd Hawkins, and N. C.
      Pedersen, Feline Pract. 23:40-44, 1995). In the present study, we have looked for
      additional FCoV-CCV recombination sites. Four regions in the pol gene were
      selected for comparative sequence analysis of the type II FCoV strains 79-1683
      and 79-1146, the type I FCoV strains TN406 and UCD1, the CCV strain K378, and the
      TGEV strain Purdue. Our data show that the type II FCoVs have arisen from double
      recombination events: additional crossover sites were mapped in the ORF1ab
      frameshifting region of strain 79-1683 and in the 5' half of ORF1b of strain 79
      1146.

PMID- 9557751
TI  - Theiler's virus infection of perforin-deficient mice.
AB  - Theiler's virus, a murine picornavirus, infects the central nervous systems of
      C57BL/6 mice and is cleared after approximately 10 days by a process which
      requires CD8+ cytotoxic T cells. We used perforin-deficient C57BL/6 mice to test
      the role of this protein in viral clearance. Perforin-deficient mice died from
      viral encephalomyelitis between days 12 and 18 postinoculation. They had high
      levels of viral RNA in their central nervous systems until the time of death. In
      contrast, viral RNA had disappeared by day 11 postinoculation in wild-type
      C57BL/6 mice. Cytotoxic T cells can kill infected cells by two main mechanisms:
      the secretion of the pore-forming protein perforin or the interaction of the Fas
      ligand with the apoptosis-inducing Fas molecule on the target cell. Our results
      demonstrate that clearance of Theiler's virus from the central nervous system in
      C57BL/6 mice is perforin dependent.

PMID- 9557752
TI  - Identification of a putative receptor for porcine reproductive and respiratory
      syndrome virus on porcine alveolar macrophages.
AB  - To identify the receptor which may determine the macrophage tropism of porcine
      reproductive and respiratory syndrome virus (PRRSV), monoclonal antibodies (MAbs)
      against porcine alveolar macrophages (PAM) were produced. Two MAbs (41D3 and
      41D5) which completely blocked PRRSV infection of PAM were further characterized.
      It was found that they reduce the attachment of PRRSV to PAM and
      immunoprecipitate a 210-kDa membrane protein from PAM. This protein was detected
      on the cell membranes of PAM but not of PRRSV-nonpermissive cells. A
      colocalization was found between the reactive sites of MAb 41D3 and PRRSV on PAM
      membranes. All PRRSV-infected cells in tissues of experimentally infected pigs
      reacted with MAb 41D3. Taken together, all these data suggest that the identified
      210-kDa membrane protein is a putative receptor for PRRSV on porcine macrophages.

PMID- 9557753
TI  - Single amino acid insertion in loop 4 confers amphotropic murine leukemia virus
      receptor function upon murine Pit1.
AB  - Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline
      leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a
      receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related
      isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch of amino
      acids named region A was identified in Pit1 (residues 550 to 558 in loop 4) as
      critical for GALV and FeLV-B receptor function. We have here investigated the
      role of region A in A-MuLV and 10A1 entry. Insertion of a single amino acid in
      region A of mouse Pit1 resulted in a functional A-MuLV receptor, showing that
      region A plays a role in A-MuLV infection. Moreover, the downregulation of 10A1
      receptor function by changes in region A of human Pit1 indicates that this region
      is also involved in 10A1 entry. Therefore, region A seems to play a role in
      infection by all viruses utilizing Pit1 and/or Pit2 as receptors.

PMID- 9557754
TI  - Processing of the Borna disease virus glycoprotein gp94 by the subtilisin-like
      endoprotease furin.
AB  - Open reading frame IV (ORF-IV) of Borna disease virus (BDV) encodes a protein
      with a calculated molecular mass of ca. 57 kDa (p57), which increases after N
      glycosylation to 94 kDa (gp94). The unglycosylated and glycosylated proteins are
      proteolytically cleaved by the subtilisin-like protease furin. Furin most likely
      recognizes one of three potential cleavage sites, namely, an arginine at position
      249 of the ORF-IV gene product. The furin inhibitor decRVKRcmk decreases the
      production of infectious BDV significantly, indicating that proteolytic cleavage
      of the gp94 precursor molecule is necessary for the full biological activity of
      the BDV glycoprotein.

PMID- 9557755
TI  - Influenza virus-infected epithelial cells present viral antigens to antigen
      specific CD8+ cytotoxic T lymphocytes.
AB  - We have investigated the mechanisms involved in the clearance of viral infection
      at the epithelium level by analyzing the activity of influenza virus-specific
      cytotoxic T lymphocytes (CTL) against virus-infected CMT-93 intestinal epithelial
      cells. Epithelial cells infected with live influenza virus effectively present
      viral antigens and were lysed by both homotypic and heterotypic influenza virus
      specific CD8+ T cells. These results shed new light on the control of viral
      infection through the elimination of virus-infected epithelial cells by virus
      specific CTL and demonstrate that CMT-93 cells furnish an appropriate model for
      in vitro evaluation of CTL activity against virus-infected epithelial cells.

PMID- 9557756
TI  - Molecular evidence for nosocomial transmission of human immunodeficiency virus
      from a surgeon to one of his patients.
AB  - We have investigated the molecular evidence in favor of the transmission of human
      immunodeficiency virus (HIV) from an HIV-infected surgeon to one of his patients.
      After PCR amplification, the env and gag sequences from the viral genome were
      cloned and sequenced. Phylogenetic analysis revealed that the viral sequences
      derived from the surgeon and his patient are closely related, which strongly
      suggests that nosocomial transmission occurred. In addition, these viral
      sequences belong to group M of HIV type 1 but are divergent from the reference
      sequences of the known subtypes.

PMID- 9557757
TI  - Identification of hepatitis G virus particles in human serum by E2-specific
      monoclonal antibodies generated by DNA immunization.
AB  - In order to elucidate the structure and morphology of hepatitis G virus (HGV), a
      recently isolated flavivirus, we generated a panel of eight monoclonal antibodies
      (MAbs) against the putative second envelope protein (E2) following DNA
      immunization. The MAbs were shown to be specific for four different epitopes on
      recombinant E2. MAb Mc6 was the only antibody able to detect the linear epitope
      LTGGFYEPL. In addition, Mc6 was able to immunoprecipitate viral particles in
      human blood samples as detected by reverse transcription-PCR amplification of HGV
      RNA. This precipitation could be competed by addition of saturating amounts of
      the linear peptide or abolished by addition of Nonidet P-40. We conclude that,
      albeit lacking the N-terminal sequence of a functional core protein, HGV builds
      classical viral particles displaying E2 envelope protein on their outer surfaces.

PMID- 9557758
TI  - Ablation of teflon granuloma with the free-electron laser emitting in the eight-
      to nine-micron range.
AB  - In this study, we developed a rat model for Teflon granuloma and used this model
      to evaluate the removal of the granuloma at laser wavelengths at which Teflon has
      a maximal absorption. Twenty-four Teflon granulomas were created in 12 rats, and
      the gross and histologic effects from laser incision at four different
      wavelengths (8.25, 8.5, 8.75, and 10.6 microm) were evaluated acutely and at 7
      and 14 days postoperatively. Polytetrafluoroethylene, or Teflon, is a relatively
      inert substance that has been used over the past 4 decades for endoscopic
      injection into the thyroarytenoid muscle of the larynx for the purposes of
      laryngeal rehabilitation in cases of unilateral vocal fold paralysis or
      incomplete glottic closure. In certain cases in which formation of granulomatous
      reaction to the Teflon occurs, patients may have significant dysphonia or airway
      compromise. Once Teflon has infiltrated the surrounding tissue planes, it is
      exceedingly difficult to remove endoscopically. Endoscopic removal of this
      granuloma is usually attempted with the carbon dioxide (CO2) laser and has had
      limited success. Examination of the infrared absorption spectrum of
      polytetrafluoroethylene reveals strong absorption in the mid-infrared region in
      the 8- to 9-microm range, with minimal absorption at 10.6 microm. Therefore, this
      absorption spectrum predicts a more efficient vaporization of Teflon at
      wavelengths near 8.5 microm. Using the free-electron laser to generate 8.25-, 8.5
      , and 8.75-microm laser light, we found Teflon granuloma ablation was far
      superior to CO2 laser ablation at 10.6 microm. The 8.25-, 8.5-, and 8.75-microm
      wavelengths selectively ablated Teflon granuloma with minimal to no collateral
      thermal injury to tissue. The differences in thermal effects observed while
      actually using the lasers were confirmed histologically.

PMID- 9557759
TI  - Pharmacologic inhibition of collagen in an experimental model of subglottic
      stenosis.
AB  - Subglottic stenosis occurs as a complication of prolonged endotracheal intubation
      secondary to inflammation with development of scar tissue and subsequent
      fibrosis. Collagen I and III levels increase during the healing process. Steroids
      alter the inflammatory response, decreasing recruitment of macrophages and
      fibroblasts. Beta-aminopropionitrile (betaAPN) inhibits the development of
      collagen cross-linking. A mechanism that would minimize hypertrophic scarring was
      sought. Eighteen dogs were anesthetized, had tracheostomies performed, and later
      had cautery of the mucosa and inner layer of the cricoid cartilage. Of 18
      survivors, 6 animals were used as controls, 6 animals received oral Decadron, 2
      mg/d, and 6 animals received oral betaAPN, 40 mg/d. There were 9 early deaths--5
      in the steroid group. Animals were painlessly sacrificed, and the specimens were
      sectioned at the cricoid cartilage level and were stained immunohistochemically
      for antibodies to collagen types I to VI. Analysis of the area of scar and the
      intensity of stain was performed with Mocha image analysis software. Collagen III
      increased in control animals to 14.38 +/- 1.85 (intensity stain index), but this
      reaction was reduced by betaAPN (5.77 +/- 1.78, p < .01). Steroids had no
      significant effect on formation of any type of collagen. Lathyrogens (betaAPN)
      may offer a pharmacologic tool to reduce scar tissue.

PMID- 9557760
TI  - Unilateral versus bilateral botulinum toxin injections in adductor spasmodic
      dysphonia.
AB  - Thyroarytenoid injection of botulinum toxin is the therapy of choice in spasmodic
      dysphonia. However, there is no convincing evidence as to whether unilateral or
      bilateral injections are to be preferred. For this reason, a prospective study
      was designed in which voice quality, duration of effect, and side effects were
      assessed. Twenty-seven patients with adductor spasmodic dysphonia were treated
      with percutaneous injections of botulinum toxin. The first treatment consisted of
      injection of 5 units in the left thyroarytenoid muscle. The second treatment, 2.5
      units in both sides, took place when the effect of the first procedure had
      completely ceased. All patients underwent both procedures. By means of self
      rating scales, effects and side effects were assessed over at least 3 months.
      There was no difference between the procedures in duration of voice improvement,
      nor in the occurrence of breathy dysphonia. After a bilateral injection,
      statistically more patients reported swallowing problems. However, most patients
      preferred the bilateral injection, in spite of more and longer-lasting side
      effects.

PMID- 9557761
TI  - Endoscopic management of pediatric posterior glottic stenosis.
AB  - Open laryngofissure with posterior cartilage grafting is advocated by some as the
      main treatment for posterior glottic stenosis in children. Endoscopic
      arytenoidectomy has been tried and recommended for bilateral vocal cord paralysis
      in children, but little published experience exists in its use for the treatment
      of pediatric posterior glottic stenosis. We describe our experience with this
      technique in 11 children ages 2 to 12 years, 6 of whom were under the age of 5
      years. Nine of 11 patients at the initial surgery were tracheotomy-dependent; 2
      others had previous laryngofissure with cartilage grafting, but continued to
      suffer from severe airway limitations. Modified carbon dioxide laser
      arytenoidectomies resulted in decannulation in 5 of 9 children and marked
      improvements in the 2 children without tracheotomies, as documented by flow
      volume loops and symptoms. Endoscopic arytenoidectomy, in our experience, is not
      as successful as open techniques described in previously published series of
      children, and requires multiple procedures due to the regrowth of granulation
      tissue. However, endoscopic repair is a viable option for low-grade stenosis and
      does not preclude an open repair in the future. It is also useful as an
      adjunctive procedure to augment the repair from an open approach.

PMID- 9557762
TI  - Method for removing endobronchial beads.
AB  - The development of rigid bronchoscopes, Hopkins rod telescopes, and optical
      forceps has increased the efficacy and safety of removing endobronchial foreign
      bodies. These instruments have become the method of choice for managing the
      majority of foreign bodies. Spherical foreign bodies, such as beads, remain
      difficult to manage. Securing the foreign body by passing a Fogarty catheter
      through the lumen, inflating the balloon, and trapping the foreign body between
      the balloon and the bronchoscope allows controlled removal.

PMID- 9557763
TI  - Laryngeal radionecrosis versus recurrent cancer: a clinical approach.
AB  - A group of 38 patients was studied by positron emission tomography utilizing
      fluorine18-labeled deoxyglucose (FDG-PET) scanning to examine the ability to
      differentiate postirradiation laryngeal recurrent cancer from radionecrosis. The
      resulting 79% correct diagnosis showed the technique to be far superior to
      conventional computed tomography scanning (61%) and clinical examination (43%).
      An algorithmic approach to evaluating and treating patients with radionecrosis
      and/or recurrent cancer by utilizing FDG-PET scanning is presented.

PMID- 9557764
TI  - Corniculate-cuneiform flap for reconstruction in the extended vertical partial
      laryngectomy.
AB  - The extended vertical partial laryngectomy involves removal of the vocal cord and
      adjacent arytenoid cartilage. Arytenoid sacrifice predisposes the patient to
      postoperative aspiration, since adequate laryngeal closure during swallowing
      cannot be accomplished. Various techniques have been previously described for
      reconstruction of this defect. We present five patients who had reconstruction of
      this area with a local, mucosally based corniculate-cuneiform flap. All patients
      were decannulated, had no long-term aspiration, maintained socially acceptable
      voice quality, and had no tumor recurrence with a minimum of 3 years of follow
      up. Our preliminary data suggest that this flap can be used in previously
      irradiated patients. The corniculate-cuneiform flap is an effective method of
      reconstruction in patients undergoing an extended vertical partial laryngectomy.

PMID- 9557765
TI  - Long-term excitability and fine tuning of nerve pedicles reinnervating strap
      muscles in the dog.
AB  - Contraction of paralyzed striated muscles has been restored by stimulating
      reinnervating pedicles with currents of low intensity. In order to allow clinical
      application, stable, long-term excitability must emulate the parameters necessary
      for the stimulation of normal motor nerves. In 6 dogs, the ansa hypoglossi nerve
      was implanted into the contralateral denervated sternohyoid muscle and surrounded
      with a bipolar cuff electrode. Three of the reinnervating pedicles were
      chronically paced with a Medtronic Itrel II Multiprogrammable Pulse Generator
      (0.5 V, 0.2 second on [30 pulses per second, 0.21-millisecond pulse width], 2.9
      seconds off). At reexploration after 8 months (6 months for 1 dog), frank
      contraction confirmed by electromyography tracings occurred in all animals with
      currents in the range of 0.1 to 0.5 mA. Muscle force was further manipulated by
      selective release of blocking currents (600 Hz, 1.7 to 0.4 mA) superimposed over
      regular stimulation (50 Hz, 0.3 to 1.7 mA). Nerve and muscle vitality were
      histologically confirmed. Long-term, low-intensity conduction capabilities, fine
      tuning, good tolerance of implanted electrodes, and lack of fatigue suggest that
      reinnervating pedicles may be successfully used for pacing when clinically
      indicated.

PMID- 9557766
TI  - Airflow and pressure characteristics of three different tracheostoma valves.
AB  - Tracheoesophageal speakers can achieve speech without digital occlusion by using
      a tracheostoma valve. Laryngectomized patients who are successful with this
      device can regain considerable freedom. However, little is known about which
      valve suits the patient best. Valve aerodynamics may give a guideline for its
      use. Three major tracheostoma valves, each divided into four subtypes, were
      repeatedly measured in this study. Dynamic pressure and airflow rate signals were
      sampled through an analog-digital interface into a computer. Considerable
      aerodynamic differences were observed between the tested valves. The maximum
      airflow rates, closing pressures, and resistances at low velocities were
      compared. The presented data may help increase the successful use of tracheostoma
      valves in tracheoesophageal speakers. Patient factors and additional valve
      factors should always be taken into account. Further clinical study to validate
      the clinical relevance of the data is needed.

PMID- 9557767
TI  - Correlations between pathologic changes in the stapes and conductive hearing loss
      in otosclerosis.
AB  - The goal of this temporal bone study was to quantify the relationship between
      specific histologic changes at the stapes footplate and the magnitude of the air
      bone gap in otosclerosis. The study material comprised 26 specimens with
      otosclerosis and 37 age-matched controls. Detailed anatomic measurements were
      made on each histologic section through the stapes footplate in each bone,
      resulting in 30 different measurement parameters for each bone. For frequencies
      250 to 2,000 Hz, the conductive hearing loss correlated highly with (p < .01) and
      appeared to be caused primarily by narrowing and loss of the annular ligament,
      especially at the posterior stapediovestibular joint space. The size of the air
      bone gap appeared to be determined by the extent and degree of this pathologic
      change. Schuknecht's hypothesis that bony ankylosis of the footplate would be
      associated with an air-bone gap of >30 dB was supported by our data. However, the
      degree and extent of bony footplate ankylosis could not be reliably predicted by
      the size of the air-bone gap.

PMID- 9557768
TI  - Role of superoxide dismutase in otitis media with effusion.
AB  - The concentration of superoxide dismutase (SOD) in middle ear effusion (MEE) was
      measured by the electron spin resonance trapping method in order to clarify the
      role of SOD in otitis media with effusion (OME) in children. The SOD levels in
      mucoid MEEs were significantly higher than those in serous and purulent MEEs.
      There was no significant difference in the levels of SOD between neutrophil
      dominant MEEs and mononuclear cell-dominant MEEs, and the levels were negatively
      correlated with the number of neutrophils in the MEEs. Moreover, the levels were
      significantly increased in patients having recurrence of MEE within 3 months
      compared with patients without recurrence of MEE. Although it is known that SOD
      plays an important role in protecting the host from oxygen radicals, the findings
      in this study suggest that SOD might be related to the chronicity of OME.

PMID- 9557769
TI  - Management of unilateral vocal cord paralysis by injection medialization with
      teflon paste. Quantitative results.
AB  - This paper prospectively analyzes eight patients who were selected for injection
      medialization of a unilateral vocal cord paralysis by a transcutaneous technique.
      Preoperative and postoperative videolaryngoscopic recordings of the position of
      the paralyzed cord were made with a scoring system correlated to the laryngeal
      airflow measurements. Quantitative acoustic recordings of the patient's voice
      were also taken and compared with the patient's own subjective analysis of his or
      her voice. Results indicate that Teflon injection by the transcutaneous method
      gives a statistically and clinically improved voice in the short term.

PMID- 9557770
TI  - Loss of cochlear nucleus neurons following aminoglycoside antibiotics or cochlear
      removal.
AB  - This study compared the effects of aminoglycoside ototoxicity and surgical
      ablation of the cochlea in infancy on the survival of neurons in the rat cochlear
      nucleus (CN). Ototoxicity was induced by a single, systemic dose of gentamicin
      sulfate and furosemide on postnatal day 6 (P6), P7, or P10, and assessed by the
      elevation of auditory brain stem response thresholds, as described in a companion
      paper. Unilateral cochlear removals were performed under Saffan anesthesia on P6,
      P9, and P12. Rats were painlessly sacrificed in adulthood, and the formalin
      perfused brains and cochleas were embedded in wax, sectioned, and stained.
      Ototoxic treatment at P6 through P10 did not reduce neuron counts in the CN.
      Cochlear removal at P6 resulted in a 40% loss of CN neurons, but removal at P12
      did not result in CN neuron loss. These data suggest that the critical period for
      the dependence of CN neurons on afferent input from the cochlea ends at the same
      time that susceptibility to aminoglycoside ototoxicity begins.

PMID- 9557771
TI  - Effects of head rotation on pharyngeal function during normal swallow.
AB  - This study quantified the effects of head rotation on pharyngeal swallowing in
      healthy subjects. Videofluoroscopic and oropharyngeal manometric examinations of
      pharyngeal swallowing were performed on seven volunteers with the head in neutral
      and rotated positions. Videofluoroscopic study revealed that head rotation
      swallow causes the bolus to lateralize away from the direction of head rotation.
      Pharyngeal manometric study indicated that the pharyngeal peak pressures toward
      the side of head rotation were significantly increased, whereas the pharyngeal
      pressures opposite the side of head rotation were not affected. Head rotation
      swallow produced a significant fall in upper esophageal sphincter (UES) resting
      pressure and a delay in UES closing. We concluded that the head rotation swallow
      in normal subjects not only alters the bolus pathway, but also has a useful
      effect on both pharyngeal clearance and UES dynamics.

PMID- 9557773
TI  - Pneumoparotitis: a new diagnostic technique and a case report.
AB  - Pneumoparotitis is a rare cause of parotid gland swelling. We report a case of
      self-induced pneumoparotitis that resulted in subcutaneous emphysema and
      pneumomediastinum after an open biopsy of the parotid gland. We suggest a new
      method for diagnosing this condition. This is done by insufflation of the cheeks
      with contrast in the oral cavity. A reflux of air and contrast is subsequently
      demonstrated by a computed tomography scan of the area.

PMID- 9557774
TI  - Pneumo-membranous labyrinth: an unusual complication of a stapedectomy.

PMID- 9557772
TI  - Human olfactory mucosa in schizophrenia.
AB  - Recent evidence indicates that developmental anomalies may underlie some symptoms
      of schizophrenia, while psychophysical studies have demonstrated olfactory
      deficits in this disease. The postmortem olfactory mucosa of elderly
      schizophrenic patients was examined to characterize the molecular phenotype of
      this tissue. The distribution of developmentally regulated cytoskeletal proteins,
      a synaptic vesicle protein, a neural marker protein, a receptor for trophic
      molecules, axonal guidance and cell migration proteins, and neuronal and glial
      cytoskeletal proteins of various degrees of phosphorylation was examined by
      immunohistochemistry. Both schizophrenic and control subjects exhibited
      dystrophic neurites that were immunoreactive for synaptophysin, microtubule
      associated proteins (MAP1B), and neurofilament proteins. No major histochemical
      or morphologic differences in either the expression or distribution of these
      proteins were observed in the olfactory epithelium of schizophrenic compared to
      control subjects. These studies indicated that dystrophic neurites frequently
      occurred in the olfactory mucosa of both schizophrenics and neurologically normal
      adults. The absence of major immunocytochemical abnormalities suggested that
      olfactory deficits in schizophrenia may be due to more subtle cellular or
      molecular differences or to abnormalities in olfactory regions of the central
      nervous system rather than in the olfactory epithelium.

PMID- 9557775
TI  - Tracheal diverticulum presenting with recurrent laryngeal nerve paralysis.

PMID- 9557776
TI  - Traumatic pseudoaneurysm: a possible early lesion in the spectrum of epithelioid
      hemangioma/angiolymphoid hyperplasia with eosinophilia.
AB  - We describe a vascular lesion that develops secondary to trauma (pseudotraumatic
      aneurysm) and study its relation to epithelioid hemangioma (EH)/angiolymphoid
      hyperplasia with eosinophilia (ALHE). Four lesions are described, all with a
      distinct history of trauma to the site from which they arose. They presented with
      masses in the subcutaneous tissue of the head. They were studied by
      immunohistochemical methods to identify their component cells. The lesions all
      demonstrated marked thickening of the wall of small and medium-sized arteries,
      with capillary vascular proliferations. One lesion demonstrated increased
      eosinophils. Myxoid changes were noted in all lesions. We hypothesize that these
      lesions may represent an early form of EH/ALHE.

PMID- 9557777
TI  - Nodular melanosis due to epithelial neoplasms: a finding not restricted to
      regressed melanomas.
AB  - Nodular or tumoral melanosis consists of nodular or sheetlike deposits of
      melanophages in the dermis. When nodular melanosis is present, a completely
      regressed malignant melanoma is a major diagnostic consideration. We present a
      case of nodular melanosis due to regression of a pigmented basal cell carcinoma
      with pilar differentiation. In addition to this case, we present five additional
      cases of epithelial neoplasms with melanin deposition in the stroma. In each
      case, the source of the melanin was non-neoplastic dendritic melanocytes
      intermingled among the tumor cells. Therefore, if nodular melanosis is found,
      pigmented epithelial neoplasms should also be considered in the differential
      diagnosis.

PMID- 9557778
TI  - Primary malignant melanoma with rhabdoid features: a histologic and
      immunocytochemical study of three cases.
AB  - Malignant rhabdoid tumors are morphologically characterized by the presence of
      sheets of large polygonal cells with abundant cytoplasm containing eosinophilic
      inclusions. They have vesicular nuclei, often with prominent central nucleoli.
      The term rhabdoid tumor was originally coined to describe a group of rare,
      aggressive renal neoplasms of childhood. Since then, similar lesions, so-called
      extrarenal malignant rhabdoid tumors have been increasingly reported. The
      evidence to date suggests that, at least in extrarenal locations, rhabdoid tumors
      do not constitute a homogeneous entity, but rather represent the shared
      morphological pattern of a diverse range of malignant neoplasms. Although such
      rhabdoid features are not uncommon in metastatic malignant melanoma, they have
      only once been briefly described in a primary lesion. We report three further
      cases of cutaneous primary malignant melanoma with rhabdoid morphology.

PMID- 9557779
TI  - Histologic differentiation of desmoplastic melanoma from cicatrices.
AB  - Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma that can be
      very difficult to diagnose correctly both clinically and histologically. The
      problem is compounded by the fact that many lesions persist at previous biopsy or
      excision sites so that scar tissue is often present admixed with or adjacent to
      the spindle cell neoplasm which may exhibit fibroblastic differentiation itself.
      In order to assess this problem, we compared and contrasted the histologic
      features of six DMM with 15 examples of cicatrices from various sources. Mature
      scars were readily differentiated from DMM by light microscopy. In contrast,
      immature scar and DMM had many features in common including hypercellularity,
      nodular lymphoid infiltrates, myxoid stroma, and atypical nuclei. The presence of
      a melanocytic proliferation within the epidermis above the dermal component,
      neurotropism, and S-100 and/or HMB-45 positivity of neoplastic cells were the
      only features that permitted reliable differentiation between the two. Clinical
      correlation and review of previous biopsy specimens are crucial in preventing a
      delayed diagnosis of DMM. Re-excision is advised in all questionable cases.

PMID- 9557780
TI  - Which direction do nevus cells move? Abtropfung reexamined.
AB  - In 1893, Unna published his theory of Abtropfung in which he suggested that
      melanocytic nevus cells originate in the epidermis and drop off into the dermis.
      We studied 3,534 nevi from patients of all ages to reassess this almost sacred
      concept. If Unna was correct, one would expect that in childhood most nevi would
      be junctional, while in late adult life almost all nevi would be intradermal. In
      our series, no child under age 10 had a purely junctional nevus, 52% had compound
      nevi, and 48% had dermal nevi. In patients older than age 60, 12% had junctional
      nevi, 23% had compound nevi, and 65% had dermal nevi. Our data fail to support
      the concept of Abtropfung; they fit better with the contradictory theory of
      upward migration of nevus cells.

PMID- 9557781
TI  - Stromelysin-3: a potent marker for histopathologic differentiation between
      desmoplastic trichoepithelioma and morphealike basal cell carcinoma.
AB  - Histopathological differentiation between desmoplastic trichoepithelioma (DTE)
      and morphealike basal cell carcinoma (BCC) is a difficult problem because of
      their similar morphological features. The matrix metalloproteinase stromelysin-3
      (ST-3), which is expressed as a specific fibroblastic factor especially
      surrounding carcinoma cells, was studied in these both conditions of wholly
      different clinical outcome. Using formalin-fixed paraffin-embedded tissues, we
      found positive immunoreactivity for ST-3 in fibroblastic cells surrounding
      morphealike BCC cells in 34 (68%) of 50 cases, whereas the epithelial tumor cells
      themselves were negative. In none of the 12 cases of DTE did we observe
      expression of ST-3 in fibroblasts. We conclude that the antibody against ST-3
      protein is an immunohistochemical marker to distinguish morphealike BCC from DTE.

PMID- 9557783
TI  - Fibronectin and the extracellular matrix in the perforating disorders of the
      skin.
AB  - Despite detailed microscopic descriptions and clinical observation, little is
      known regarding the pathogenesis of the perforating disorders of skin, which have
      traditionally been subdivided into numerous microscopic entities associated with
      various clinical settings. An increasing body of evidence now suggests that the
      perforating disorders of skin are akin, and may constitute an expanded single
      pathologic entity. Each of the classic perforating disorders of skin, including
      elastosis perforans serpiginosa, perforating folliculitis, reactive perforating
      collagenosis, Kyrle's disease, and perforating disorder of uremia, have been
      shown to extrude collagen, elastin, and related extracellular matrix components
      through the epidermis. Considering a shared pathogenic mechanism among these
      entities, we explored the possible role of the extracellular matrix, in
      particular fibronectin, in perforating disorders of skin. Using
      immunohistochemical and serum determinations of extracellular matrix
      constituents, including fibronectin, collagen type IV, laminin, and tenascin, we
      showed consistent serum elevation and/or deposition of fibronectin, in each case,
      without a commensurate increase in laminin, collagen type IV, and tenascin. We
      propose that elevated serum and tissue concentrations of fibronectin may be
      responsible for inciting, in a physiologically aberrant manner, increased
      epithelial migration and proliferation culminating in perforation.

PMID- 9557782
TI  - Cytotoxic T cells in basal cell carcinomas of skin.
AB  - Previous studies have suggested the importance of CD8+ cytotoxic T-cells of hosts
      against neoplasms. Earlier studies and our previous investigation showed that a
      majority of tumor infiltrating T-cells in human basal cell carcinomas (BCCs)
      belonged to CD4+ T-cells. CD8+ cells were also present in the peritumor areas of
      human BCCs, but in smaller numbers. Published evidence indicates the importance
      of cytotoxic T-cells in antitumor immunity. Cytotoxic T-cells have been
      identified by using monoclonal antibodies against various cytotoxic T-cell
      components. In this study, we used monoclonal antibodies to perforin to evaluate
      the role of cytotoxic T-cells in the host response against basal cell carcinomas.
      Perforin-expressing T-cells could be identified in the infiltrate of BCCs in
      frozen tissue sections, and also in antigen-retrieved paraffin-embedded sections
      of BCCs, and the presence of perforin-expressing T-cells correlated with the
      infiltration of CD8+ T-cells. These results suggest that cytotoxic T-cells play a
      role in host defense against human BCCs.

PMID- 9557784
TI  - Automated measurement of melanoma cross-sectional area.
AB  - The object of this study was to evaluate the prognostic impact of a cross
      sectional area measured in routinely stained slides of cutaneous melanoma using
      fully automated image analysis. Hematoxylin-eosin stained slides of 238 specimens
      of primary cutaneous melanoma with Clark levels III to V were evaluated by
      digital image analysis using color video images, a scanning stage, and autofocus
      equipment. The cross-sectional area was significantly related to metastasis-free
      survival. Lesions with a cross-sectional area < or = 12 mm2 showed a 2-year
      metastasis-free survival rate of 92+/-2% compared with 41+/-8% in lesions with a
      cross-sectional area > 12 mm2 (log rank test: z = 71, p < 0.0001). The same was
      true for overall survival (98+/-1% compared with 82+/-6%; z = 42.12, p < 0.0001).
      In multivariate analysis, the cross-sectional area seems to provide prognostic
      information in addition to that provided by Breslow's index. In cases with
      regression and in small melanomas with vertical growth, however, metastatic
      spread may occur in lesions with a small cross-sectional area. It was concluded
      that automated measurement of the cross-sectional area may be helpful in
      assessing prognosis in cutaneous melanoma.

PMID- 9557785
TI  - Estrogen and progesterone receptors in androgenic alopecia versus alopecia
      areata.
AB  - In some situations, hair growth is under hormonal control. Androgenic alopecia is
      characterized as hormonally driven hair loss in the genetically susceptible
      individual. During pregnancy, hair growth is increased, as estrogen appears to
      prolong the anagen phase. However, postpartum hair loss is common, and thus may
      be related to a decrease in estrogen and or progesterone levels. In contrast,
      alopecia areata is not considered to be under hormonal control. We compared the
      immunohistochemical staining characteristics of nine cases of androgenic alopecia
      with those of 13 cases of alopecia areata using estrogen receptor (ER) and
      progesterone receptor (PR) markers. Estrogen receptor positivity in the dermal
      papilla was found in only two of 13 cases of alopecia areata, and in one case of
      androgenic alopecia. Six of 13 cases of alopecia areata demonstrated focal
      reactivity with the progesterone marker in a similar location, while only three
      cases of androgenic alopecia showed positivity with this antibody. Examination of
      the perifollicular fibroblasts for the ER marker showed positivity in one of 13
      cases of alopecia areata and in one case of androgenic alopecia. Two cases of
      alopecia areata revealed focal staining in this location for the PR marker, while
      the androgenic alopecia cases failed to stain. These results indicate that
      estrogen and progesterone receptor expression is not significantly increased or
      decreased in the pilosebaceous units or surrounding mesenchymal cells in
      androgenic alopecia vs. alopecia areata. Therefore, an indirectly mediated
      process of estrogen/progesterone control on hair growth and development must be
      presumed for cases of androgenic alopecia.

PMID- 9557786
TI  - Expression of proliferating cell nuclear antigen (PCNA) and apoptosis related
      antigen (LeY) in epithelial skin tumors.
AB  - We semiquantitatively analyzed expression of PCNA and LeY in seborrheic keratosis
      (SK), actinic keratosis (AK), Bowen's disease (BD), and squamous cell carcinoma
      (SCC), using immunocytochemically stained tissue sections. PCNA expression
      increased in a stepwise fashion from low levels in normal skin to higher
      expressions within SK, AK, BD, and SCC. The levels of LeY protein also increased
      in this order. The PCNA expression pattern shifted from expression limited to the
      basal and suprabasal cell layers (in normal skin and SK) to expression extending
      to the upper squamous and granular layers (in AK, BD, and SCC). On the other
      hand, the pattern of LeY expression shifted from the granular (in normal skin) to
      the upper squamous (in SK and AK) and suprabasal layers (in BD and SCC). These
      findings suggest that PCNA expression is related to the degree of cell
      proliferation and that LeY expression is related to the degree of differentiation
      or keratinization of tumor cells. In addition, PCNA and LeY show a reciprocal
      relationship in their expression.

PMID- 9557787
TI  - Vesiculo-bullous dermatomyositis.
AB  - Cutaneous manifestations of dermatomyositis (DM) commonly include Gottron's
      papules, cuticular erythema and telangiectasia, periorbital edema with a
      "heliotrope" rash, a papulosquamous eruption of the hairline, face, and trunk, as
      well as poikiloderma. Very few references can be found concerning vesicular and
      bullous lesions, however. We present two patients with dermatomyositis who
      manifested vesicular and bullous lesions who were initially misdiagnosed.
      Although rare, it is important to recognize this form of DM to avoid
      misdiagnosis. Furthermore, in some cases, vesiculo-bullous DM may portend a poor
      prognosis.

PMID- 9557788
TI  - Sarcoidal foreign-body granulomatous dermatitis associated with ophthalmic drops.
AB  - Sarcoidal granulomas are found in sarcoidosis and in reactions to foreign
      materials. We report the case of an 81-year-old woman with glaucoma who presented
      with multiple brown-black asymptomatic papules over the chin and involving nasal
      mucosa and columella of 1-year duration. Biopsy of the nasal mucosa and cutaneous
      papules showed sarcoidal granulomas associated with brown-black intracellular
      pigment within multinucleated giant cells. Electron-probe x-ray microanalysis
      demonstrated high sulfur content. Clinical studies showed no evidence of systemic
      sarcoidosis. Two of three ophthalmologic drops contained sodium bisulfite;
      bisulfite is known to cause allergic reactions. Although the exact substance
      causing the granulomatous reaction is unknown, the distribution of the lesions-
      nasal mucosa and columella (via the nasal lacrimal duct) and the underlying chin-
      implicate the eyedrops in the production of the pigmented granulomatous nodules.

PMID- 9557789
TI  - Grover's-like disease in the setting of bone marrow transplantation and
      autologous peripheral blood stem cell infusion.
AB  - Four cases of a Grover's-like disease in patients with leukemia/lymphoma, who
      underwent high-dose chemotherapy and either allogeneic/autologous bone marrow
      transplantation or autologous stem cell infusion, are described. Three of four
      patients had fever prior to the onset of their rash. In addition to suprabasilar
      clefts, acantholysis, and dyskeratosis, typical of Grover's disease, there was a
      chemotherapeutic effect in the form of keratinocytes with atypical nuclei. So
      called "starburst cells," which have been purported to be specific for high-dose
      etoposide (VP-16) therapy, were seen in two cases, but only one of these patients
      received etoposide. In one patient with clinical vesicles, direct
      immunofluorescence ruled out paraneoplastic pemphigus. In conjunction with 18
      similar cases in the literature, the following conclusions were reached: (a) the
      pathogenesis probably involves the combined effects of fever (with sweating),
      occlusion, and chemo/radiation therapy; (b) no single chemotherapeutic agent can
      be consistently implicated; and (c) in addition to graft-versus-host disease, the
      eruption of lymphocyte recovery, and other cutaneous eruptions in the setting of
      bone marrow transplantation, the differential diagnosis includes paraneoplastic
      pemphigus, which direct immunofluorescence excludes.

PMID- 9557790
TI  - Cutaneous malakoplakia in a patient with acquired immunodeficiency syndrome
      (AIDS).
AB  - Malakoplakia is an uncommon granulomatous lesion that afflicts predominantly
      immunocompromised individuals but is extremely rare in acquired immunodeficiency
      syndrome (AIDS). We report a case of cutaneous malakoplakia in an AIDS patient
      that presented as a banal right axillary abscess which resolved after excision
      and drainage. The rarity of malakoplakia in AIDS may be due to a relative or
      selective preservation of antimicrobial function of monocytes. Malakoplakia is
      distinguished from other inflammatory or neoplastic lesions by the presence of
      Michaelis-Gutmann bodies. A correct diagnosis is usually made only after biopsy
      and is an indication to use antimicrobial agents with adequate cellular
      penetration and concentration.

PMID- 9557791
TI  - Benign sebaceous neoplasm with prominent epidermal component.
AB  - A 65-year-old woman presented with a solitary nodule within an erythematous
      plaque in her right groin. Histopathologic examination showed central lobular
      proliferation of basaloid cells admixed with mature sebaceous cells and a lateral
      extensive intraepidermal component composed mostly of lobules of mature sebocytes
      consistent with intraepidermal epithelioma with sebaceous differentiation and
      focal invasion. Although various cutaneous neoplasms may show an intraepidermal
      growth pattern, extensive sebaceous differentiation in such a neoplasm, as seen
      in this case, has not been described. Electron-microscopic study revealed that
      the basaloid cells have features of pluripotential cells. This observation
      supports the previously reported concept that intraepidermal epithelioma may be
      composed of a group of heterogeneous tumors with various degrees and lines of
      differentiation. Additionally, sebaceous epithelioma/adenoma should be considered
      in the differential diagnosis of the cutaneous neoplasms with an intraepidermal
      growth pattern.

PMID- 9557792
TI  - Multiple pigmented basal cell carcinomas.
AB  - Basal cell carcinoma is the most common of all skin cancers and the most
      prevalent one among Caucasians. Rarely, these tumors are seen in other races. We
      report a 77-year-old Korean woman who presented with multiple darkly pigmented
      enlarging nodules on her scalp, face, trunk, and extremities. The patient had
      first noted a 6-mm pigmented lesion on her left eyebrow 10 years previously.
      Since then, other lesions had appeared in many locations on her body. She had
      been otherwise healthy and without a history of exposure to arsenic or radiation.
      There was no family history of skin cancer, xeroderma pigmentosum, or basal cell
      nevus syndrome. On physical examination, multiple darkly pigmented dome-shaped
      papules and nodules were present on her scalp, face, right forearm, lower
      abdomen, and inguinal areas. They ranged in size from 0.5 mm to 2 cm. The larger
      ones showed central ulceration. Multiple biopsy specimens from different sites
      showed pigmented basal cell carcinomas. Clinically, there was no evidence of
      nevus sebaceus, xeroderma pigmentosum, basal cell nevus syndrome, or
      immunodeficiency. Clinical workup including chest radiography, abdominal
      ultrasound, bone scan, and brain computerized axial tomography scan did not
      demonstrate primary or secondary tumors. The results of serologic and hematologic
      tests were also within normal limits. This is an unusual case report of multiple
      pigmented basal cell carcinomas in an Asian woman without any predisposing risk
      factors.

PMID- 9557793
TI  - Painful hyperplasia and hypertrophy of pacinian corpuscles in the hand: report of
      two cases with immunohistochemical and ultrastructural studies, and a review of
      the literature.
AB  - Hypertrophy and hyperplasia of pacinian corpuscles in the hand are very rare,
      with only 29 cases previously published. We describe two new cases in middle-aged
      patients whose chief complaint was progressive digital pain. Immunohistochemical
      and electronmicroscopic investigations indicated that the lump replicates the
      structure of enlarged pacinian corpuscles and should not be considered as a real
      tumor, nor connected to neurofibromatosis. No recurrence was observed after
      surgical excision. Although local trauma was encountered in 55% of the reported
      cases, the pathogenesis of such a lesion is still speculative.

PMID- 9557794
TI  - Benign myoepithelioma of the skin.
AB  - A case of cutaneous myoepithelioma is reported. The tumor was composed of spindle
      shaped, epithelioid, and plasmacytoid (hyaline) cells. It exhibited a widespread
      immunoreactivity for low molecular weight keratins and protein S-100, being
      irregularly positive for smooth muscle actin. Ultrastructural studies of tumor
      cells showed a variable content of intermediate filaments, with focal densities
      resembling smooth muscle dense bodies. A well-developed basal lamina, pinocytotic
      vesicles, and some desmosomes were also observed. In spite of being accepted as
      an individual entity, myoepitheliomas probably belong to a family of lesions that
      include mixed tumors. Therefore, this case can be considered as a salivary-gland
      type tumor, probably originating from myoepithelial cells of sweat glands. The
      existence of this unique neoplasm provides further support to the debated role of
      myoepithelial cells in the development of mixed tumors.

PMID- 9557795
TI  - Cutaneous epithelioid angioleiomyoma.
AB  - We describe an unusual dermal neoplasm with epithelioid morphology. A 44-year-old
      man presented with a solitary, tender, 4-mm nodule on the leg. Excisional biopsy
      showed several well-circumscribed dermal epithelioid tumor nodules, prominent
      vascularity, and smooth muscle differentiation. We suggest the term cutaneous
      epithelioid angioleiomyoma for this neoplasm. In a review of the literature, we
      found reports of two similar cases and a recent report describing five cutaneous
      epithelioid leiomyosarcomas. Cutaneous epithelioid angioleiomyoma represents a
      rare variant of dermal smooth muscle tumor and could represent the benign
      counterpart to the recently described epithelioid leiomyosarcoma of the skin.

PMID- 9557796
TI  - Skin as the primary site of Hodgkin's disease: a case report of primary cutaneous
      Hodgkin's disease and review of its relationship with non-Hodgkin's lymphoma.
AB  - We report an elderly patient who presented with a single cutaneous nodule of
      primary cutaneous Hodgkin's disease (PCHD). Reed-Sternberg cells, expressing CD30
      and CD15, but not leukocyte common antigen (CD45RB), were identified in the
      neoplastic cells. Southern blot analysis failed to detect T-cell receptor or
      immunoglobulin gene rearrangement. A work-up for systemic disease at the time of
      presentation was negative, supporting the diagnosis of PCHD. Nevertheless, 1 year
      later, the disease course was complicated by the development of nodal HD and
      nonHodgkin's lymphoma (NHL). This case report supports the existence of this
      rare, but distinct, cutaneous tumor.

PMID- 9557797
TI  - Quantitative ultrasonography of the liver in cats during obesity induction and
      dietary restriction.
AB  - A study was designed to evaluate quantitative ultrasonographic characteristics of
      a diffuse parenchymal disease in an experimental model of subclinical fatty
      infiltration of the liver using diet-induced obesity and dietary restriction in
      the cat. Ultrasound images of livers were quantitatively analysed by a video
      signal analysis technique before, during and at the end of obesity induction, and
      then during and following dietary restriction. Attenuation and brightness
      (backscatter coefficient) were correlated with hepatic lipid content obtained
      from the livers by surgical and ultrasound-guided percutaneous biopsy.
      Attenuation and backscatter increased as hepatic lipid content increased. Both
      attenuation and backscatter significantly correlated with the hepatic lipid
      content (P=0.002 and P=0.02 respectively). This model of subclinical fatty
      infiltration of the liver in the cat demonstrates that hepatic lipid content
      increases as a consequence of obesity and of severe dietary restriction.
      Infiltration of the liver with fat may be evaluated non-invasively using
      quantitative ultrasonography by the video signal analysis technique. This method
      of image analysis may prove useful for the evaluation of diffuse parenchymal
      organ disease.

PMID- 9557798
TI  - Clinical biochemical parameters of the endangered Catalonian donkey breed: normal
      values and the influence of sex, age, and management practices effect.
AB  - Twelve clinical biochemical parameters were determined in 97 animals of all age
      groups and both sexes of the endangered Catalonian donkey breed. Significant sex
      differences were observed for phospholipid concentration (P<0.01). Evaluating the
      effect of management practices on the various parameters showed significant
      differences for total bilirubin (P<0.001) and creatinine (P<0.05) concentrations
      and gamma-glutamyltransferase (P<0.05) activity. Moreover, it was observed that
      inorganic phosphorus concentration decreased with age (P<0.001), whereas albumin
      and triglyceride concentrations increased with age (P<0.01 and P<0.001,
      respectively). Comparison of biochemical ranges obtained for the Catalonian
      donkey breed with reference ranges for other breeds and populations (Mammoth, USA
      donkeys, UK donkeys, Indian donkeys and Poitou donkeys), indicated that most
      values were similar, with the exceptions of enzymatic activities mainly. The
      results reported in the present study could serve as reference ranges for donkey
      populations.

PMID- 9557799
TI  - Effects of weight gain and loss on metabolic rate, glucose tolerance, and serum
      lipids in domestic cats.
AB  - Weight gain is a common problem in domestic cats, but little is known about its
      metabolic effects. The purpose of this study was to determine the effects of diet
      induced weight gain and subsequent weight loss on metabolic rate, body
      composition, and glucose tolerance. Gain of approximately 20 per cent body weight
      (divided approximately equally between fat and fat-free mass) over three months
      resulted in insulin resistance in females, indicated by increases in basal
      insulin concentration (68.2+/-7.9 to 119+/-16.5 pmol litre(-1), P<0.05), insulin
      peak response to glucose (241.1+/-31.6 to 315.0+/-23.0 pmol litre(-1), P<0.05),
      and deltaI/deltaG (14.2+/-2.6 to 18.1+/-1.3 pmol mmol(-1), P<0.05) compared with
      pre-gain values. The same numerical trend was noted in male cats, however,
      changes were not significant (P>0.05). Alterations in serum lipids included
      significant (P<0.05) elevations in triglyceride concentrations in male cats and
      decreased beta-lipoprotein concentrations in both genders. Weight loss over three
      months normalised basal insulin, insulin response to glucose, and serum
      triglyceride concentrations, and resulted in significant (P<0.05) decreases in
      serum concentrations of beta- and prebeta-lipoproteins, cholesterol, and
      triiodothyronine. Diet-induced weight gain of three months' duration, followed by
      three months' maintenance of increased body weight did not affect fasting or
      resting metabolic rate. Development and severity of impaired glucose tolerance,
      insulin resistance, and other changes may be affected by duration and possibly
      severity of weight gain.

PMID- 9557800
TI  - The isolation and purification of a dual specific mast cell-derived protease from
      parasitised caprine jejunal tissue.
AB  - A mast cell granule protease has been isolated and purified from nematode
      infected caprine jejunal homogenate by FPLC techniques and termed Goat Mast Cell
      Protease (GMCP). The purification steps were monitored for proteolytic activity
      against the synthetic substrate carboxybenzoyl-L-lysine thiobenzyl ester (BLT)
      and the presence of a homogenous protease preparation in the final sample was
      shown by SDS-PAGE electrophoresis. This protease was compared with enzymatic
      activity from isolated mucosal mast cells, which demonstrated the putative mast
      cell-derived source of the purified enzyme. Rabbit antiserum was raised against
      the protease and through the use of immunohistochemistry and Western blotting
      techniques the mast cell origin of the protease was confirmed. NH2-Terminal amino
      acid sequence analysis demonstrated a high degree of homology between GMCP and
      other previously isolated mast cell proteases including sheep mast cell protease
      (SMCP). Substrate analysis showed that GMCP also had an unusual dual chymotrypsin
      like and trypsin-like activity similar to SMCP and bovine duodenase.

PMID- 9557801
TI  - Recombinant porcine follicle stimulating hormone produced in baculovirus-insect
      cells induces rat ovulation in vivo and gene expression of tissue plasminogen
      activator in vitro.
AB  - Superovulatory responses in cattle are known to be highly variable. In the
      present study, a recombinant porcine follicle stimulating hormone (rpFSH)
      produced in baculovirus-insect cells was utilised to evaluate the role of this
      recombinant FSH in control of the ovulatory process. Immature hypophysectomised
      rats were implanted with oestrogen pellet (10 mg diethylstilbestrol) and then
      primed with pregnant mare serum gonadotropin (PMSG, 17.5 IU, sc). Fifty-two hours
      later, 100 microg rpFSH or saline was injected (sc) to induce ovulation. All rats
      that received rpFSH ovulated with about eight ova rat(-1), whereas none of the
      control animals did. Ovulation induced by rpFSH was associated with an increase
      in the ovarian activity and message levels of tissue-type plasminogen activator
      (tPA), a protease important in the preovulatory degradation of the follicle wall.
      Furthermore, addition of rpFSH to the cultured rat granulosa cells resulted in a
      significant increase in tPA enzyme activity. These results demonstrate that rpFSH
      produced in baculovirus-insect cells has biological potency in ovulation as well
      as gene expression of tPA, providing a large advantage of this massive expression
      system in the reproduction of domestic animals.

PMID- 9557802
TI  - Activity of N-acetylglucosamine-1-phosphate transferase in sheep liver
      microsomes: in vivo and in vitro inhibition by tunicamycin.
AB  - The neurological disease of livestock known as annual ryegrass toxicity, caused
      by ingestion of bacterial toxins called corynetoxins, has been shown to be
      produced experimentally by injection of tunicamycin, a related antibiotic. In
      this study the effects of tunicamycin inhibition on the activity of the enzyme, N
      acetylglucosamine-1-phosphate transferase, in sheep liver rough microsomes were
      measured in vitro and in vivo. Enzyme activity was dependent on Triton X-100 and
      exogenous dolichyl phosphate for maximal activity, although there was measurable
      activity in their absence. The transferase enzyme was very sensitive to in vitro
      (inhibition can be detected below 10 ng ml(-1)). In vivo, sheep treated
      parenterally with a single dose of tunicamycin showed a time and dose-dependent
      decrease in enzyme activity, which was almost completely inhibited for up to 14
      days after a sublethal dose of toxin. In addition, the yield of rough microsomes
      was lower from toxin-treated sheep than from control animals.

PMID- 9557803
TI  - Bisphosphonates: a potential role in the prevention of osteoporosis in laying
      hens.
AB  - Osteoporosis in layers is associated with the modelling and remodelling of
      medullary bone. Cancellous bone volume (CBV) decreases initially during medullary
      bone modelling and continues to decrease during subsequent remodelling. In an
      attempt to maintain peak structural bone mass, the bisphosphonate, alendronate,
      was administered to pullets before medullary bone modelling. At point of lay CBV
      was significantly greater (P<0.01) in the alendronate group (17.59 per cent) than
      in controls (13.79 per cent), while medullary bone volume (MBV) was not
      significantly affected. After 20 weeks, CBV remained significantly higher
      (P<0.02) in the alendronate group (12.72 per cent) than in controls (9.80 per
      cent) and MBV was lower in the alendronate group than the control group. CBV was
      however reduced and MBV increased in both groups compared with values at point of
      lay. Alendronate therefore appeared to prevent the bone loss associated with
      medullary bone modelling but not that which occurs during remodelling.

PMID- 9557804
TI  - Scrapie associated fibril detection from formaldehyde fixed brain tissue in
      natural cases of ovine scrapie.
AB  - The medulla oblongata of the brains of 71 scrapie-suspect cases were routinely
      fixed in 10 per cent formal saline and assessed for vacuolation on HE-stained
      sections. A pool of fresh brain material was also dissected from each animal and
      extracts prepared for the routine detection of scrapie-associated fibrils by
      negative stain transmission electron microscopy. The remaining formaldehyde fixed
      medulla samples, which were not used for the histological examination, were coded
      and subjected to a pretreatment with sodium borohydride and then processed using
      the routine fibril detection procedure. Of the 71 samples tested 46 were
      considered positive by all three test procedures. Sixteen samples were negative
      for all three tests. Four samples were positive by histopathological examination
      and positive for fibrils using fresh tissue, but fibrils could not be detected in
      the fixed tissue preparations. Conversely, there were five fixed samples in which
      fibrils could be detected which were negative for the other two tests. The
      fibrils observed in fixed preparations were indistinguishable from those observed
      in fresh tissue extracts. The sensitivity of the test for fibril detection using
      fixed tissue was 92 per cent and the specificity 76 per cent. It is concluded
      that scrapie-associated fibrils can be recovered from formaldehyde fixed tissue,
      as presented for routine histopathological examination, and therefore the method
      has potential in the retrospective analysis of archived brain tissue where only
      fixed material was stored.

PMID- 9557805
TI  - Effects of dobutamine on isovolumic and ejection phase indices of cardiac
      contractility in conscious healthy dogs.
AB  - The aim of this study was to determine cardiac contractility using indices
      derived from cardiac catheterisation in conscious healthy dogs during dobutamine
      infusion. Eight dogs were studied. An ECG was recorded together with left
      ventricular pressure and volume which were measured using a conductance catheter
      with an integrated microtip pressure sensor. Eight indices of left ventricular
      systolic performance were derived from these records. Measurements were realised
      under basal conditions and during an incremental dobutamine challenge. The
      maximal rate of rise in ventricular pressure (max dP/dt), max dP/dt divided by
      the developed pressure and the mean systolic ejection rate were the most
      sensitive indices to detect dobutamine induced changes in contractility with
      maximal percentage changes of 122+/-11 per cent, 130+/-7 per cent and 102+/-24
      per cent respectively. Ejection fraction increased significantly during
      dobutamine infusion (maximal percentage change of 43+/-9 per cent) whereas the
      pre-ejection period (PEP) and the left ventricular ejection time (LVET) decreased
      significantly (maximal percentage change of -41+/-2 per cent and -28+/-3 per cent
      respectively). All these six indices were significantly correlated with each
      other. Conversely, the ratio PEP/LVET and the LVET corrected for heart rate
      dependency showed a maximal percentage change of only -10+/-1 per cent and -16+/
      7 per cent, respectively, during the dobutamine infusion and were not
      significantly correlated with the other contractility indices. This study
      demonstrated the feasibility of the conductance method to determine cardiac
      contractility in conscious healthy dogs submitted to a pharmacological stress
      testing and provides control values for eight indices of left ventricular
      contractility during dobutamine infusion at increasing dosages.

PMID- 9557806
TI  - Effects of transport and indomethacin on telemetered body temperature and release
      of cortisol and prolactin in pre-pubertal pigs.
AB  - Previous research indicates that acute physical stress (restraint) raises core
      temperature in growing pigs via a prostaglandin-dependent mechanism. This study
      investigated whether transport stress affects body temperature in pigs and
      whether any such changes might involve endogenous prostaglandins. Pre-pubertal
      boars (n = 7) were implanted with venous catheters and biotelemetry devices for
      the measurement of core temperature. They were transported for two hours, with
      and without indomethacin (IND) pre-treatment, and blood samples were taken at 15
      minute intervals for the determination of plasma cortisol and prolactin
      concentrations. The results indicated that, contrary to predictions, body
      temperature tended to fall during transport and that the effect was exaggerated
      by IND. By contrast, cortisol concentrations increased during transport and were
      unaffected by IND whereas the tendency for transport to stimulate prolactin
      release was reversed by IND.

PMID- 9557807
TI  - Variations in effectiveness of antigen retrieval pretreatments for diagnostic
      immunohistochemistry.
AB  - Enzymatic and non-enzymatic pretreatments for antigen retrieval (AR) on formalin
      fixed, paraffin-embedded, deparaffinised sections were compared and optimised by
      immunostaining of tissues infected with 13 different pathogens. Enzymatic
      pretreatment was achieved by incubating slides in 0.25 per cent trypsin (TR) and
      non-enzymatic pretreatments by heating them in a microwave oven (MWO) or an
      autoclave (AC). Three different buffers of different pH and molarity including
      phosphate buffer (PB), citrate buffer (CB) and acetate buffer (AB) were used as
      AR solutions. All of them were effective regardless of molarity, for the MWO with
      a processing time of 20 minutes, and the AC with a processing time of 15 minutes.
      The detectability of many viral antigens was significantly improved by MWO or TR
      pretreatment, but that of most bacterial antigens was not improved and that of
      some viral antigens was decreased by TR pretreatment. These results suggest that
      AR pretreatment is a prerequisite procedure for immunohistochemical detection of
      many infectious agents but the optimal pretreatment has to be individualised for
      each agent.

PMID- 9557808
TI  - Medullary bone and humeral breaking strength in laying hens.
AB  - To test the hypothesis that large amounts of medullary bone in the humeral
      diaphysis may increase breaking strength, various parameters of bone quality and
      quantity were examined in two large flocks of hens near end of lay. We conclude
      that the amount of medullary bone in the humerus of hens during the laying period
      influences bone strength. This medullary bone may not have any intrinsic
      strength, but may act by contributing to the fracture resistance of the
      surrounding cortical bone. Using a quantitative, low dose, radiographic
      technique, we can predict, from early in the laying period, those birds which
      will develop large amounts of medullary bone in their humeri by the end of the
      laying period. The formation of medullary bone in the humeral diaphysis is not at
      the expense of the surrounding radiographed cortical bone.

PMID- 9557809
TI  - Plasma pharmacokinetics of intravenous and intramuscular furosemide in the camel
      (Camelus dromedarius).
AB  - Single bolus intravenous (i.v.) and intramuscular (i.m.) doses of furosemide (1.5
      mg kg(-1)) were administered in a crossover design to three female and three male
      adult, dromedary camels. Plasma furosemide concentrations were assayed by HPLC
      and sodium, potassium and chloride concentrations were measured using ion
      selective electrodes. Plasma furosemide concentration-time plots indicated multi
      compartment disposition, and there was considerable intersubject variability in
      the pharmacokinetic parameters. The mean (SD) i.v. terminal elimination half-life
      was 118 (67) minutes. The systemic clearance was 5.4 (1.2) ml min(-1) kg(-1). and
      the steady-state volume of distribution was 0.43 (0.14) litre kg(-1). The mean
      absorption time after i.m. dosing was 33 (62) minutes, while the absolute
      bioavailability was 71 (20) per cent. The glucuronide metabolite of furosemide
      was not detected in plasma. Clearance was lower, volume of distribution was
      larger, and half-life was longer compared with published data for dogs, horses,
      rats and humans. Plasma potassium and sodium concentrations were significantly
      diminished (P<0.05) by an average of 35.6 per cent (two to six hours post-dose)
      and 11.3 per cent (eight hours post-dose), respectively. Plasma chloride
      concentrations were not significantly affected by furosemide administration.

PMID- 9557810
TI  - Effect of administration of a novel recombinant bovine interferon on length of
      oestrous cycle in cattle.
AB  - In ruminants, extensive reproductive loss occurs during the process of maternal
      recognition of pregnancy and it has been suggested that trophoblast interferons
      may be potential therapeutic agents. This paper reports results from a trial
      using eight first lactation Holstein-Friesian heifers to test the efficacy of a
      novel recombinant bovine interferon produced in bacteria in extending the life of
      the corpus luteum. Oestrus was synchronised in these animals and 0.1 mg of this
      non-glycosylated interferon was infused into the uterus twice daily for 13 days
      starting approximately 12 days after oestrus. This treatment resulted in an
      extension of the lifespan of the corpus luteum by 5.5 days (P=0.028) compared
      with untreated controls. In these animals the interovulatory period was extended
      by 6.4 days (P=0.009). Administration of this protein did not have any adverse
      effects either on body temperature or on daily milk yields. The results indicate
      that this novel interferon may have potential therapeutic application for
      reducing embryo mortality.

PMID- 9557811
TI  - Effect of a novel recombinant bovine interferon and trophoblast secretory
      products on protein metabolism by endometrial explants from cattle and sheep.
AB  - The effect of a novel recombinant bovine interferon on the rate of protein
      synthesis, as measured by the rate of leucine incorporation, in endometrial
      explants from cows and ewes was investigated and compared with the effect of
      trophoblast secretory proteins and of a recombinant bovine interferon-alpha1.
      Exposure of cultured bovine endometrial tissue to the novel recombinant bovine
      interferon mimicked the effect of pregnancy in reducing the rate of protein
      synthesis in both caruncular and intercaruncular endometrium. This effect was
      similar to that seen with naturally produced trophoblast secretory proteins and
      it was more pronounced than that seen when endometrial tissue was treated with a
      related recombinant bovine interferon-alpha1. Ovine endometrial cultures were
      unaffected by exposure to this novel recombinant bovine interferon. This novel
      recombinant interferon exhibited potent antiviral properties (an activity of 1.6
      x 10(10) international reference units/mg protein) and may prove to be a valuable
      reagent in studying the maternal recognition of pregnancy in the cow and reducing
      embryo mortality.

PMID- 9557812
TI  - Nitric oxide as the final metabolic mediator of cervical ripening.

PMID- 9557813
TI  - Clinical application of nitric oxide donors and blockers.

PMID- 9557814
TI  - Nitric oxide--another factor in cervical ripening.

PMID- 9557815
TI  - Cervical ripening after nitric oxide.

PMID- 9557816
TI  - Clinical andrology.

PMID- 9557817
TI  - Urgently wanted for ICSI: clinical andrologists.

PMID- 9557818
TI  - Andrology and clinical sciences.

PMID- 9557819
TI  - Current problems with spermatid conception.

PMID- 9557820
TI  - Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK
      137 316: establishment of a regimen that permits normal menstrual cyclicity.
AB  - Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low
      dose regimen of the potent new antiprogestin ZK 137 316, which permits continued
      menstrual cyclicity but alters gonadal-reproductive tract activity, was
      established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n =
      8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C
      1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during
      cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the
      0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent
      progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was
      accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3,
      half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group
      were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5
      in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic
      follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01
      mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily
      administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation
      was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized
      pituitary function and resulted in anovulation and amenorrhoea. A chronic low
      dose regimen of the antiprogestin ZK 137 316, which permits normal
      ovarian/menstrual cyclicity, has potential as a contraceptive in women.

PMID- 9557821
TI  - Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin
      ZK 137 316: morphometric assessment of the uterus and oviduct.
AB  - The long-term effects of the antiprogestin ZK 137 316 on reproductive tract
      morphology in rhesus macaques were investigated. The monkeys were injected daily
      (i.m.) for five menstrual cycles with vehicle or 0.01, 0.03 or 0.1 mg ZK 137
      316/kg body weight. Reproductive tracts (n = 3/ group) were collected during the
      mid-luteal phase (day 8) of the fifth cycle in the control, 0.01 and 0.03 mg/kg
      groups, or 6-7 days after the oestradiol peak in the 0.1 mg/kg group. ZK 137 316
      treatment resulted in a dose-dependent atrophy of the endometrium, marked by
      reduced mitotic activity in the glands, compaction of the stroma, degradation of
      spiral arteries and dilation of veins. There was no effect of ZK 137 316 on
      myometrial or oviductal weight. Treatment with 0.1 and 0.03 mg/kg, but not 0.01
      mg/kg resulted in fully ciliated and secretory oviducts, indicating a dose
      dependent blockade of progesterone antagonism of oestrogen-dependent oviductal
      differentiation. In the endometrium, the suppressive action of progesterone on
      oestrogen and progestin receptors was also blocked by ZK 137 316 in a dose
      dependent manner. However, endometrial atrophy appeared due to inhibition of
      progesterone action together with a blockade of oestrogen-dependent
      proliferation. The profoundly suppressed endometrium produced by chronic low-dose
      ZK 137 316 treatment is unlikely to support implantation. Such treatment may
      therefore provide a novel contraceptive modality.

PMID- 9557822
TI  - Somatotropic axis and body weight in pre-menopausal and post-menopausal women:
      evidence for a neuroendocrine derangement, in absence of changes of insulin-like
      growth factor binding protein concentrations.
AB  - The altered function of the somatotropic axis observed in perimenopause may
      underlie the changes in body weight and fat distribution. The aim of the present
      study was to evaluate, in pre-menopausal and post-menopausal women with body mass
      index (BMI) > or = or <25, the basal plasma levels of growth hormone (GH),
      insulin-like growth factor (IGF)-I and -II, IGF binding protein (IGFBP)-1 and -3,
      and the response of GH and IGFBP-1 and -3 to GH releasing hormone (GHRH) and GHRH
      plus arginine tests. GH and IGF-I basal concentrations were significantly higher
      in pre-menopausal than in post-menopausal women, while IGF-II, IGFBP-1 and IGFBP
      3 concentrations did not vary significantly. IGFBP-1, but not IGFBP-3,
      concentrations were higher in lean than in obese patients. Insulin concentrations
      were significantly higher in obese patients, while no differences were observed
      between pre-menopausal and post-menopausal women. In all subjects, GH
      concentrations increased significantly during GHRH test; pre-menopausal and lean
      women showed a higher response compared to post-menopausal and obese women. The
      GHRH plus arginine test stimulated GH response in all women, irrespective of age
      and BMI. IGFBP-1 and -3 concentrations did not vary in response to GHRH or GHRH
      plus arginine tests. The somatotropic axis undergoes modifications in post
      menopausal women, apparently not involving IGFBP-1 and -3. Arginine infusion
      restores the response of GH to GHRH, in both post-menopausal and obese subjects.
      A somatostatinergic hyperactivity at the climateric period may underlie the
      changes both in body weight and somatotropic axis.

PMID- 9557823
TI  - Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in
      fluid from human stimulated follicles.
AB  - Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) play an
      important role in regulating follicle growth and maturation. We have evaluated
      whether responsiveness to gonadotrophins during an in-vitro fertilization (IVF)
      treatment is related to follicular fluid IGF-I and IGFBP-3 concentrations. We
      also investigated if a difference is present in IGF-I and IGFBP-3 concentrations
      between patients treated with human menopausal gonadotrophin (HMG) and patients
      treated with highly purified follicle stimulating hormone (FSH). We have measured
      IGF-I and IGFBP-3 in follicular fluid from pre-ovulatory follicles in an IVF
      programme. All 70 patients were stimulated after being down-regulated with a
      gonadotrophin-releasing hormone (GnRH) analogue. IGF-I concentrations in
      follicular fluid were significantly inversely correlated with the number of
      ampoules FSH administered and number of days of FSH administration, and
      significantly correlated with the number of follicles aspirated. IGFBP-3
      concentrations were not correlated with any other parameter measured nor were IGF
      I and IGFBP-3 concentrations correlated. IGFBP-3 concentrations were
      significantly higher in patients receiving highly purified FSH compared with
      patients receiving HMG (P < 0.005). These results are new evidence that IGF-I
      concentration in follicular fluid is higher in women who respond better to
      follicular stimulation, i.e. women who grow many follicles, women who need a
      shorter duration of stimulation and women who need fewer ampoules FSH before
      oocyte retrieval.

PMID- 9557825
TI  - First established pregnancy after controlled ovarian hyperstimulation with
      recombinant follicle stimulating hormone and the gonadotrophin-releasing hormone
      antagonist ganirelix (Org 37462).
AB  - This case report describes the first established pregnancy after the use of
      gonadotrophin-releasing hormone (GnRH) antagonist, ganirelix (Org 37462;
      Organon), to prevent a premature luteinizing hormone surge during ovarian
      hyperstimulation with recombinant human follicle stimulating hormone (rhFSH). The
      pregnancy progressed normally and ended with the birth of a healthy boy and a
      girl after an elective Caesarean section at gestational age of 37 weeks. This
      case illustrates, for the first time, the use of a GnRH antagonist in combination
      with a pure FSH preparation for ovarian stimulation.

PMID- 9557824
TI  - Polycystic ovary syndrome: anomalies in progesterone production.
AB  - The underlying cause of anovulation and miscarriage in polycystic ovary syndrome
      (PCOS) is unknown. Progesterone may play an important role in oocyte
      fertilization and embryo implantation. Therefore, in this study we analyse the
      endocrine function of luteinizing granulosa cells to synthesize progesterone in
      vivo and in vitro in PCOS and normal patients participating in an in-vitro
      fertilization programme. Human luteinizing granulosa cells were obtained from 10
      patients with normal ovaries (controls) and 10 patients with PCOS by follicular
      aspiration of individual follicles of each patient and pooled in an attempt to
      obtain three groups: cells from follicle sizes < or =10,>10< or =15 and > or =16.
      Serum concentrations of oestradiol and progesterone on the day of human chorionic
      gonadotrophin (HCG) injection were significantly higher (P < 0.01 and P < 0.05)
      in PCOS patients than in controls. After HCG stimulation, in-vitro progesterone
      production was enhanced in granulosa cells of the control group and
      concentrations increased with follicular size as expected. However, the
      concentration of progesterone of PCOS patients did not increase with follicular
      size and there was a significant difference between normal and PCOS groups in
      follicles >10< or =15 mm (P < 0.05) and > or =16 mm (P < 0.01). Oestradiol
      production was increased in follicles > or =16 mm in both groups, although this
      did not reach significance. In summary, it seems that PCOS granulosa cells
      demonstrate an abnormal capacity to synthesize progesterone in vivo and in vitro.
      The understanding of granulosa cell function in PCOS may explain the anovulation
      and miscarriage that occurs in these patients.

PMID- 9557826
TI  - Increase of large granular lymphocytes in human ejaculate containing antisperm
      antibodies.
AB  - Using flow cytometry, we studied the expression of the CD16 antigen by
      lymphocytes present in human semen samples from three groups of patients: 60
      fertile men attending for vasectomy, 60 sterile patients without antisperm
      antibodies (ASA) and 18 immunological sterile patients with ASA in their
      ejaculate. No significant difference was found in the concentration of leukocytes
      or subpopulations of these cells (monocytes, lymphocytes and granulocytes)
      between fertile, sterile without ASA and immunological sterile groups. However,
      we detected a predominance of macrophages/monocytes within the population of
      seminal leukocytes. No statistically significant difference was found in the
      absolute number of T and B lymphocytes between the three groups studied. However,
      a significant increase in the number of CD16+ lymphocytes was observed in the
      ejaculate of sterile patients with ASA as compared to the other groups. This
      finding might establish an important parameter in the follow-up and prognosis of
      patients with immunological sterility.

PMID- 9557827
TI  - High frequency of well-defined Y-chromosome deletions in idiopathic Sertoli cell
      only syndrome.
AB  - Idiopathic Sertoli cell-only syndrome (SCOS) is characterized by azoospermia,
      small testes, absence of germ cells in the testes, elevated follicle stimulating
      hormone and normal testosterone concentrations. The Y-chromosome is involved in
      the regulation of spermatogenesis and in the pathogenesis of a fraction of
      idiopathic male infertility. An azoospermia factor (AZF) is present on the Y
      chromosome long arm euchromatic region (Yq11) and two gene families (DAZ and RBM)
      have been identified within this region. The aim of this study was to investigate
      whether a specific pattern of Yq11 microdeletions may be associated with
      idiopathic SCOS. Eighteen idiopathic subjects showing a testicular cytological
      picture of bilateral SCOS were selected and tested by polymerase chain reaction
      for a set of 29 Y-specific sequence-tagged sites (STS). We found Yq
      microdeletions in 10 out of 18 patients (55.5%) while the fathers or brothers of
      six out of 10 patients deleted for Yq were shown to carry an intact Y-chromosome.
      These deletions may therefore be considered as de-novo deletions and the cause of
      SCOS. The analysis of the microdeletions allowed us to identify two homogeneous
      regions that have a high incidence of deletion. The smallest deletion, common to
      all patients, is located in Yq interval 5. We therefore speculate that there is a
      relationship between specific, well-characterized Yq11 microdeletions and a
      testicular picture of SCOS, identifying an Y-related region frequently deleted in
      this syndrome. In conclusion, the findings of this study demonstrate that a large
      percentage of idiopathic SCOS may be genetically determined and identify an Y
      related region that seems to possess one or more still unknown genes essential
      for spermatogenesis.

PMID- 9557828
TI  - Efficiency of MicroSort flow cytometry for producing sperm populations enriched
      in X- or Y-chromosome haplotypes: a blind trial assessed by double and triple
      colour fluorescent in-situ hybridization.
AB  - Using fluorescent in-situ hybridization (FISH) we have evaluated, on a blind
      basis, the efficiency of flow cytometry to separate human X- and Y-chromosome
      bearing spermatozoa. Our data demonstrate that human spermatozoa can be sorted to
      a purity of 80-90% for X spermatozoa and of 60-70% for Y spermatozoa. Our results
      using triple FISH fully agree with the sorting treatment used in each case and
      corroborate the efficiency of the flow sorting technique for sperm sex selection.
      In these limited samples (200-500 sperm/donor), the frequencies of disomic or
      diploid spermatozoa were not increased when comparing the sorted samples with
      unselected samples or with our control series.

PMID- 9557829
TI  - Origin and mechanisms of non-disjunction in human autosomal trisomies.
AB  - Chromosomal aneuploidy is one of the major causes of pregnancy wastage. In this
      review we summarize the knowledge about the origin and mechanisms of non
      disjunction in human autosomal trisomies 8, 13, 15, 16, 18, and 21, accumulated
      during the last decade by using DNA polymorphism analysis. Maternal meiosis I non
      disjunction is the most important single class, but chromosome-specific patterns
      exist. For the acrocentric chromosomes 15 and 21, meiosis I errors predominate
      among the maternal errors, in contrast to trisomy 18 where meiosis II errors
      predominate. For trisomy 16, virtually all cases are due to maternal meiosis I
      non-disjunction. Postzygotic (mitotic) non-disjunction constitutes 5-15% of cases
      of trisomies 15, 18, and 21, whereas for trisomy 8 and trisomy 8 mosaicism the
      majority of cases are due to mitotic non-disjunction. For paternal non
      disjunction of chromosomes 18 and 21, meiosis II or mitotic errors predominate.
      There is aberrant meiotic recombination associated with maternal meiotic non
      disjunction in all trisomies studied in detail so far. Advanced maternal age
      remains the only well documented risk factor for maternal meiotic non
      disjunction, but there is, however, still a surprising lack of understanding of
      the basic mechanism(s) behind the maternal age effect.

PMID- 9557830
TI  - Prenatal diagnosis of Fukuyama-type congenital muscular dystrophy by
      microsatellite analysis.
AB  - We applied microsatellite analysis to prenatal diagnosis of Fukuyama-type
      congenital muscular dystrophy (FCMD), an autosomal recessive severe muscular
      dystrophy associated with brain malformations. Recent identification of the FCMD
      gene locus at 9q31-q33 provided the basis for prenatal diagnosis and carrier
      detection. We recently developed new microsatellite markers which are closer to
      the FCMD gene and improved the phenotype probability. Nine fetuses in eight
      unrelated FCMD families, including a twin pregnancy, were analysed using the
      newly developed markers. Four fetuses showed over 99% probability of being
      healthy either as normal homozygote (n = 1) or heterozygote carrier (n = 3) and
      were born without signs of FCMD. The other five fetuses were diagnosed with a
      probability of FCMD of 99% or greater; all of the latter parents decided to
      terminate the pregnancies. Brain malformations characteristic of FCMD in one of
      the aborted fetuses confirmed the diagnosis of FCMD at 19 weeks of gestation.

PMID- 9557831
TI  - Laparoscopic management of organic ovarian cysts: is there a place for frozen
      section diagnosis?
AB  - Only benign ovarian cysts can be treated by laparoscopic surgery. Although
      clinical examination and the results of pre-operative work-up do make a real
      contribution in indicating the benign or malignant nature of cysts, only
      histology can provide the absolute diagnosis. In this context, the goal of this
      study was to establish whether there is any advantage in performing frozen
      section during laparoscopic surgical management of organic ovarian cysts. Between
      January 1989 and March 1996, 228 patients underwent an adnexectomy for an ovarian
      mass. After the pre-operative work-up and the diagnostic phase of laparoscopy, 26
      patients (11.4%) presented with suspected signs of malignancy restricted purely
      to the ovary. These 26 patients underwent a laparoscopic adnexectomy with
      extraction of the excised tissues using an endoscopic bag, followed by frozen
      section. For all these patients the results of the frozen section concluded that
      the lesion was benign. In every case the definitive histological results
      confirmed the frozen section findings. This strategy enabled us to avoid
      laparotomy, especially for the nine post-menopausal patients whose adnexal masses
      appeared to be complex by ultrasound. These encouraging preliminary results need
      to be confirmed by a larger series of patients, so as to specify the place of
      frozen section in the laparoscopic surgical management of organic ovarian cysts.

PMID- 9557833
TI  - Effect of parental age on fertilization and pregnancy characteristics in couples
      treated by intracytoplasmic sperm injection.
AB  - The purpose of this study was to investigate any influence of maternal and/or
      paternal age on gamete characteristics and pregnancy outcomes in intracytoplasmic
      sperm injection (ICSI) cycles. In all, 821 consecutive ICSI cases were analysed
      retrospectively. While a significant linear decline in semen volume was detected,
      no significant differences in the concentration, motility or morphology of the
      spermatozoa were found with paternal ageing. A significant decline in the number
      of oocytes retrieved and the number of mature oocytes obtained was found with
      advancing maternal age. An increase in the occurrence of digyny was noted with
      parental ageing, while no difference in single or bipronuclear fertilization was
      found. Older women had a decreased incidence of single pronucleus formation and
      an increase in digyny, but no significant difference in the percentage of oocytes
      that underwent two-pronuclear fertilization was detected with regard to maternal
      ageing. Pregnancy outcomes were not influenced by the age of the male partner,
      while a strong negative correlation was found with maternal ageing. To better
      analyse male partner ageing as a factor affecting pregnancy outcome, we analysed
      a subgroup of patients with a female partner aged <35 years who underwent ICSI.
      No paternal influence on ICSI pregnancy outcome was found in this subgroup of
      patients. We conclude that the influence on pregnancy outcome after ICSI is
      related mostly to maternal and not paternal age.

PMID- 9557832
TI  - The role of transvaginal ultrasonography in the detection of pelvic pathologies
      in the infertility workup.
AB  - To assess the efficiency of transvaginal ultrasonography (TVUS) in the screening
      of pelvic pathologies in the initial workup of infertile women, we carried out a
      prospective comparison of sonographic diagnosis with laparoscopic and
      pathological findings. Between February 1994 and April 1995, 133 premenopausal
      non-pregnant women underwent TVUS on the day before laparoscopy. The efficiency
      of TVUS in detecting pelvic pathologies was 90.2% with a sensitivity of 86.2%, a
      specificity of 97.8% and positive and negative predictive values of 98.6 and
      78.8% respectively. If the six false-negative cases with a histological diagnosis
      of minimal endometriosis were defined as 'normal pelvis', sensitivity and
      specificity could be corrected to 92.5 and 98.6% respectively. Endometriomas were
      diagnosed by TVUS with an efficiency of 96.4%, with a sensitivity and a
      specificity of 90 and 96.7 % and with positive and negative predictive values of
      75 and 99.1% respectively. The sensitivity of vaginal sonographic
      characterization of pelvic adhesions was 61.1% with a specificity and positive
      predictive value of 98.2 and 84.6%. The negative predictive value of TVUS was
      94.1%. These data suggest that it is not possible to characterize pelvic
      adhesions, especially filmy adhesions, with acceptable accuracy. However, in the
      initial workup of infertile women, if the patient is young, if both
      hysterosalpingography and TVUS are negative, laparoscopy could be postponed. In
      couples with severe male factor infertility and for whom in-vitro fertilization
      or intracytoplasmic sperm injection is the treatment of choice, laparoscopy might
      be avoided where the TVUS is negative.

PMID- 9557834
TI  - Cumulative pregnancy rates and selective drop-out of patients in in-vitro
      fertilization treatment.
AB  - The validity of the cumulative pregnancy rate (CPR) calculated by life-table
      approach, obtained in a transport in-vitro fertilization (IVF) programme, was
      tested by the determination of possible influence of selective drop-out of
      patients with a poor treatment prognosis. A cohort of 1211 patients who had a
      first IVF cycle was followed, and the CPR after three IVF cycles was assessed.
      First cycles of patients who discontinued treatment after failed IVF, and of
      those who did not achieve a pregnancy but proceeded to a subsequent cycle, were
      compared for fertilization rate and for occurrence of prognosticators of poor
      treatment outcome: oocyte yield < or =2, and replacement of <2 embryos. The CPR
      after three cycles was 54.9%. No differences were found in the first and second
      cycles of patients who continued treatment and those who dropped out. Selective
      drop-out of patients with a poor treatment prognosis was not found. Therefore,
      although calculations of CPR using life-table analysis generally overestimate the
      real probability of pregnancy after successive IVF cycles, the calculated CPR
      after three IVF cycles gives a reliable indication of the chance of occurrence of
      a pregnancy for the population studied.

PMID- 9557835
TI  - Transient retardation in embryo growth in normal female mice made pregnant by
      males whose testes had been heated.
AB  - In three separate experiments, using three different strains of mice, when normal
      females were mated by males whose testes had been heated once to 42 degrees C for
      20 min, the embryos at 10.5 days post-coitum were approximately 20% smaller than
      control embryos. In one experiment, the difference was still present, although
      proportionately less, at 15.5 and 18.5 days and, in another experiment, a
      difference could be seen in 11.5 and 13.5 day old embryos but not in 12.5, 14.5,
      15.5 or 18.5 day old embryos. The frequency of mating and pregnancy rates were
      unaffected. In one experiment, the time available for mating was restricted to 4
      h instead of overnight, without effect on the result. In another experiment,
      other males were heated for 30 min, and these showed a period of infertility from
      10 to 32 days later, preceded and followed by the production of smaller than
      normal embryos; litter size was also reduced in the period after the return of
      fertility in these animals. The yolk sacs and the trophoblasts of the embryos
      sired by the heated males were also slightly smaller than those sired by the
      controls in the two experiments in which these were measured. The pattern of
      weight reduction is thus different from that seen in gynogenetic embryos or when
      the gene for insulin-like growth factor (IGF)-II is disrupted, and suggests a
      reduction in embryo growth at the earlier stages, with compensatory growth
      occurring later in pregnancy.

PMID- 9557836
TI  - Comparison of the fertilizing capability of spermatozoa from ejaculates,
      epididymal aspirates and testicular biopsies using intracytoplasmic sperm
      injection.
AB  - A prospective study was carried out to compare the fertilizing capability and
      pregnancy outcome following intracytoplasmic sperm injection (ICSI) using
      spermatozoa obtained from ejaculates, or surgically from epididymis or
      seminiferous tubules. A total of 77 ICSI cycles (one per patient) was included.
      In all, 28 patients had severe oligoasthenoteratozoospermia, 19 patients had
      obstructive azoospermia and 30 patients had non-obstructive azoospermia. The main
      outcome measures were fertilization rate per injected metaphase II oocyte and the
      clinical pregnancy rate per embryo transferred back to the female recipients. In
      patients with severe oligoasthenoteratozoospermia, the fertilization and
      pregnancy rates were 79 and 25 %. In patients with obstructive azoospermia, for
      whom epididymal spermatozoa were used, these were 75 and 28%, and in the non
      obstructive group for which testicular spermatozoa were used for injection, they
      were 69 and 21% respectively. These rates were not significantly different in the
      three groups (P = 0.85 and P = 0.14 respectively), suggesting that spermatozoa
      from the ejaculates and epididymal or testicular biopsies are able to fertilize
      equally by using ICSI. Live birth per embryo transfer was significantly reduced
      in patients with non-obstructive azoospermia compared to the other two groups.
      The high abortion rate (50%) in the group in which testicular spermatozoa were
      used raises doubts about the developmental competence of such embryos.

PMID- 9557837
TI  - Glutathione in spermatozoa and seminal plasma of infertile men.
AB  - Glutathione has a central role in the defence against oxidative damage; however,
      the data on glutathione concentrations in the semen of infertile men are limited.
      To expand this knowledge the glutathione content of the ejaculates and blood
      plasmas of 77 infertile men and 11 controls were analysed. The concentrations of
      total glutathione were assessed in spermatozoa, seminal plasma and blood plasma
      using a coupled spectrophotometric assay. In the spermatozoa of patients with
      oligozoospermia the glutathione concentrations (2.57+/-0.96 nmol/10[8]
      spermatozoa; mean +/- SD) were significantly lower than in the controls (3.49+/
      0.87 nmol/10[8] spermatozoa; P +/- 0.03). The glutathione content of spermatozoa
      from patients with normozoospermia showed large variations (3.04+/-1.37
      nmol/10[8] spermatozoa). An association between the intracellular glutathione
      content and the ability to penetrate bovine cervical mucus was observed (r = 0.2,
      P = 0.04). The intracellular glutathione concentrations correlated with the
      glutathione levels in seminal plasma (r = 0.46, P < 0.0001). There was no
      correlation between glutathione concentrations in blood plasma and those in
      seminal plasma or in spermatozoa. The glutathione concentrations in seminal
      plasmas did not differ between the different groups, however, correlated with the
      serum follicle stimulating hormone concentrations (r = 0.53, P = 0.005). This
      study demonstrated that intracellular glutathione levels of spermatozoa are
      decreased in certain populations of infertile men.

PMID- 9557838
TI  - The effect of colchicine treatment on sperm production and function: a review.
AB  - Colchicine is used for the treatment of various diseases including gouty
      arthritis, familial Mediterranean fever (FMF) and Behcet's disease. As a
      modulator of the microtubules at the cytoskeleton level, it arrests cell division
      at metaphase and inhibits microtubular-dependent cell motility. Controversy
      exists as to the adverse effect of colchicine on sperm production and function in
      healthy subjects as well as in gout, FMF and Behcet's patients. Sperm analysis
      shows a spectrum of pathology, from oligo- and azoospermia to normospermia with
      disturbances in sperm motility. These inconsistent sperm pathologies can be
      explained in part by the variability of the pathophysiology of the underlying
      disease. Thus, it seems that colchicine by itself may not have a significant
      direct adverse effect on sperm production and function.

PMID- 9557840
TI  - Successful treatment of idiopathic anejaculation with electroejaculation after
      microsurgical vas aspiration.
AB  - This case report describes a couple suffering from infertility secondary to
      psychogenic anejaculation, which was refractory to all conservative treatment
      modalities. A first trial of microsurgical vas aspiration in combination with in
      vitro fertilization (IVF) resulted in a pregnancy. After 2 years, three more
      trials of microsurgical vas aspiration in combination with either IVF or subzonal
      insemination (SUZI) resulted in embryo transfer without pregnancy. Finally, after
      3 years, spermatozoa obtained by rectal probe stimulation under general
      anaesthesia were cryopreserved. A second intracytoplasmic sperm injection (ICSI)
      procedure using these cryopreserved spermatozoa also resulted in a second
      pregnancy. Although sperm concentration was in the normal range, in all samples
      obtained by either rectal probe electrostimulation or microsurgical vas
      aspiration, motility was <30% in all but two samples.

PMID- 9557839
TI  - DAZ (Deleted in AZoospermia) genes encode proteins located in human late
      spermatids and in sperm tails.
AB  - We analysed the location of proteins encoded by the DAZ (Deleted in AZoospermia)
      genes in human testis tissue and in mature spermatozoa. The DAZ genes are known
      to be expressed exclusively in the human male germ line, and are candidate genes
      for the expression of the azoospermia factor AZFc mapped recently to distal Yq11.
      They encode testis-specific RNA binding proteins, the function of which is not
      yet known. Immunostaining experiments with antibodies prepared for the specific
      peptide domain encoded by the DAZ2 transcript (formerly SPGY1) revealed the
      presence of DAZ proteins in the innermost layer of the male germ cell epithelium
      and in the tails of spermatozoa. This suggests a function for DAZ proteins in the
      RNA metabolism of late spermatids, presumably in the storage or transport of
      testis-specific mRNA, the translation of which is repressed until the formation
      of mature spermatozoa. Deletion of DAZ genes is supposed not to interfere with
      human sperm maturation but to result in a gradual reduction of mature
      spermatozoa.

PMID- 9557841
TI  - Male subfertility induced by acute scrotal heating affects embryo quality in
      normal female mice.
AB  - The aim of this experiment was to design a suitable mouse model for male
      subfertility in which to study the effect of decreased sperm quality on embryo
      quality in vivo and in vitro. To achieve male subfertility, testes of adult male
      mice were immersed in water at either 42 degrees C (heated) or 33 degrees C
      (controls) during 20 min. Twenty-eight days after treatment, all heat stressed
      males showed a significant decrease in relative testis weight [384.7 mg in
      controls (286.7-460.6) versus 323 mg in stress heated groups (117.9-405.6); P <
      0.001], sperm concentration [3.75 x 10(6)/ml (2.75-7.25) versus 1.00 x 10(6)/ml
      (0-4.00); P < 0.001] and progressive sperm motility [57.5% (48.0-79.0) versus
      42.5% (14.0-66.0); P < 0.001]. Moreover, after mating to heat exposed males, not
      only the number of pregnant females (20/22 versus 18/30) but also the weight of
      their embryos [275.4 mg (78.7-339.4) versus 261.8 mg (68.1-339.0); P < 0.001] was
      significantly lower at 14.5 days post coitum when compared to controls. Neither
      the number of resorption sites nor the number of viable embryos per pregnant
      female was significantly different between groups. Also, the in-vitro
      fertilization rate of oocytes, fertilized by spermatozoa collected from heat
      stressed males, was significantly lower (44.9%; P < 0.0001) when compared to
      controls (65.1%; P < 0.0001). In conclusion, the results of this study suggest
      that male subfertility induced by acute scrotal heating may result in impaired
      sperm quality, reduced embryo weight in vivo and decreased fertilization rate in
      vitro.

PMID- 9557842
TI  - Permeation of human ovarian tissue with cryoprotective agents in preparation for
      cryopreservation.
AB  - The recent improvements in the treatment of cancer by chemo- and radiotherapy
      have led to a significant increase in the survival rates of patients with
      malignant disease, but at the expense of distressing side effects. One major
      problem, especially for younger patients, is that aggressive therapy destroys a
      significant proportion of the follicular population, which can result in either
      temporary or permanent infertility. Freeze-banking pieces of ovarian cortex prior
      to treatment is one strategy for preserving fecundity. When the patient is in
      remission, fertility could, theoretically, be restored by autografting the thawed
      tissue at the orthotopic site or by growing isolated follicles to maturity in
      vitro. Recent studies have found good follicular survival in frozen-thawed human
      ovarian tissue but to optimize the process an effective cryopreservation method
      needs to be developed. An essential part of such a technique is to permeate the
      tissue with a cryoprotectant to minimize ice formation and the extent of this
      equilibration is an important determinant of post-thaw cellular survival. In the
      current study, we have investigated the diffusion of four cryoprotective agents
      into human tissue at both 4 degrees C and 37 degrees C. We have also studied the
      effect of adding different concentrations of the non penetrating cryoprotective
      agent, sucrose, to the freezing media using the release of lactate dehydrogenase
      as a measure of its protective effect. At 4 degrees C propylene glycol and
      glycerol penetrated the tissue significantly slower than either ethylene glycol
      or dimethyl sulphoxide. At the higher temperature of 37 degrees C all four
      cryoprotectants penetrated at a faster rate, however concern about enhanced
      toxicity prevents the use of these conditions in practice. Thus, the results
      suggest that the best method of preparing tissue for freezing is exposure for 30
      min to 1.5 M solutions of ethylene glycol or dimethyl sulphoxide at 4 degrees C;
      this achieved a mean tissue concentration that was almost 80% that of the bathing
      solution. We also report that the addition of low concentrations of sucrose to
      the freezing medium does not have a significant protective effect against
      freezing injury.

PMID- 9557843
TI  - Dithiothreitol prevents age-associated decrease in oocyte/conceptus viability in
      vitro.
AB  - The present study was designed to ascertain whether the negative effects on
      reproductive potential of post-ovulatory ageing in vitro of oocytes can be
      prevented by antioxidant therapy. Mouse metaphase II (MII) oocytes were aged in
      vitro for 12 h prior to insemination in the presence of varying concentrations of
      L-ascorbic acid, 6-methoxy-2,5,7,8-tetramethylchromane-2-carboxylic acid
      (Trolox), L-cystine dihydrochloride, ethylenediaminetetraacetic acid (EDTA), beta
      mercaptoethanol and DL-dithiothreitol (DTT). In-vitro ageing of oocytes was
      associated with lower fertilization rate, higher proportion of concepti
      exhibiting cellular fragmentation at 24 h post-insemination and lower percentage
      of concepti reaching the blastocyst stage. Ascorbic acid, Trolox and EDTA had no
      effect on cellular fragmentation or potential of oocytes for development.
      However, the probability of an oocyte reaching the blastocyst stage was decreased
      (P < or = or = 0.05) in oocytes incubated in the presence of L-cystine (50 and
      500 microM) and beta-mercaptoethanol (5, 50 and 500 microM) when compared to
      control aged oocytes. Age-associated cellular fragmentation at 24 h post
      insemination was partially prevented (P < or = 0.05) by incubating oocytes in the
      presence of beta-mercaptoethanol (500 microM). DTT (50 and 500 microM) increased
      (P < or = 0.05) fertilization rate and number of cells at 81 h post-insemination
      to levels similar to those exhibited by control oocytes. Furthermore, both age
      associated fragmentation at 24 h post-insemination (P < or = 0.05) and decreased
      potential of oocytes for development to the blastocyst stage (P < or = 0.05) were
      prevented, at least in part, by culturing oocytes in the presence of DTT (50
      microM). Although the mechanism by which DTT exerts its beneficial effects on
      aged oocytes remains to be elucidated, it may protect oocytes by preventing
      oxidation of free thiol groups and/or altering a redox-independent signalling
      pathway that mediates cellular fragmentation and death.

PMID- 9557844
TI  - Comparison of microscopic epididymal sperm aspiration and intracytoplasmic sperm
      injection/in-vitro fertilization with repeat microscopic reconstruction following
      vasectomy: is second attempt vas reversal worth the effort?
AB  - Since 1986, we have performed microscopic reconstruction in 18 men following
      failed microscopic vasectomy reversal. Between 1994 and 1996, nine couples have
      undergone microscopic epididymal sperm aspiration (MESA)/ intracytoplasmic sperm
      injection (ICSI) treatment for male infertility due either to congenital absence
      of the vas deferens (CAVD) or inoperable excurrent duct obstruction. We compared
      the cost efficiency of repeat vasectomy reversal to that for MESA combined with
      ICSI/in-vitro fertilization (ICSI/IVF). The cost of male partner procedures
      (vasectomy reversal, MESA) was based on physician and hospital charges, while the
      cost of ICSI/IVF included preparation of the female partner (medications and
      physician charges) and procedures (physician and hospital charges including
      oocyte retrieval, micromanipulation, and embryo transfer). Our cost examination
      does not include charges related to follow-up visits, prenatal monitoring,
      complications of pregnancy (i.e. miscarriage) or delivery in either group.
      Overall patency and pregnancy rates in the repeat vasectomy reversal group were
      78 and 44% respectively. The cost per delivered baby (including multiple
      metachronos deliveries per couple) was $14892. Fertilization of oocytes has been
      achieved in 37/72 (51%) and pregnancies have occurred in 6/9 (67%) attempts and
      5/9 (56%) report delivery. The average cost per pregnancy was $25637 and the
      average cost per delivered baby (or ongoing pregnancy) was $35570. The cost per
      delivery by MESA/ ICSI/IVF is 2.4 times the charges per delivery obtained through
      repeat vasectomy repair. Couples attempting to overcome infertility caused by
      vasal obstruction should be informed that vas reconstruction remains a cost
      effective means of re-establishing fertility even in men who have previously
      failed vasectomy reversal.

PMID- 9557845
TI  - Post-ovulatory ageing of the human oocyte and embryo failure.
AB  - We carried out a prospective study of 221 healthy women who were attempting
      pregnancy. During the study, women collected daily urine samples and kept daily
      records of intercourse. Ovulation and early pregnancy losses were later
      identified by immunoassays of urinary human chorionic gonadotrophin and steroid
      metabolites. We have used these data to examine whether the risk of early
      pregnancy loss was higher with post-ovulatory ageing of the oocyte. 192
      pregnancies were ranked by the probability that the oocyte might have aged before
      fertilization. There was a statistically significant increase in the risk of
      early loss as the likelihood of oocyte ageing increased (P < 0.05). No similar
      risk was observed for clinical miscarriages. Post-ovulatory ageing of the oocyte
      prior to fertilization may cause early pregnancy failure in humans as it does in
      several other mammalian species.

PMID- 9557846
TI  - Effect of phosphate on the second cleavage division of the rat embryo.
AB  - Development of the rat embryo is arrested at the 2-cell stage in vitro in the
      presence of inorganic phosphate (Pi). Rat embryos were affected by exposure to
      1.19 mM KH2PO4 in modified hamster embryo culture medium-1 at the late 2-cell
      stage only. When exposure durations were 6 h, embryos whose exposure timings were
      prior to cleavage had a reduced rate of development to the blastocyst stage (2
      8%) when compared with embryos with no exposure to Pi (97%, P < 0.05). When
      exposure durations were 18 h, all embryos were arrested at the 2- to 4-cell
      stage. These timings would correspond to the G2 to M phase of the second cell
      cycle. Maturation-promoting factor (MPF), which is regulated by a phosphorylation
      cascade, controls cell division, and its kinase activity is necessary in order
      for the cell to enter the M phase. However, the histone H1 kinase activity levels
      and the patterns of the state of phosphorylation of cdc2 were the same in blocked
      and non-blocked embryos. Because MPF was active in blocked embryos, the
      developmental block in rat 2-cell embryos caused by phosphate was not due to MPF
      activity or its phosphorylation cascade.

PMID- 9557847
TI  - Predictive value of the results of a first in-vitro fertilization cycle on the
      outcome of subsequent cycles.
AB  - This study examines the relationship between the first cycle of in-vitro
      fertilization (IVF) and subsequent cycles. The results of all IVF cycles
      conducted at The Hammersmith Hospital or The Royal Masonic Hospital between 1988
      and 1995 were studied including those cycles where egg recovery was abandoned due
      to poor ovarian response. All patients underwent a standardized treatment
      protocol. Of those women who achieved a clinical pregnancy during their first IVF
      attempt, 33% achieved a pregnancy during their second cycle, statistically
      significantly different from the 24% of patients conceiving during a second cycle
      who had failed to conceive during their first. 36% of those who achieved a
      biochemical pregnancy in their first cycle became pregnant in their second. Age
      was an important factor in the success of IVF treatment, with pregnancy rates of
      48% in the 20-25 year age group falling to 8% in those aged > or =41 years.
      Cumulative pregnancy rates were 26% after one cycle, increasing to 43% after two
      cycles and reached 80% after seven cycles. A previous pregnancy significantly
      improved a couple's probability of conception in a later IVF cycle. Overall
      pregnancy rates per cycle were constant for the first three attempts. Cumulative
      pregnancy rates continued to rise to 72% after six cycles. Thus the more cycles a
      couple undergo (up to six) the greater their chance of a pregnancy.

PMID- 9557848
TI  - A prospective, randomized, double-blind study for the evaluation of assisted
      hatching in patients with advanced maternal age.
AB  - The objective of this study was to determine if assisted hatching improved the
      rates of implantation, clinical pregnancy and ongoing pregnancy for in-vitro
      fertilization (IVF) patients aged > or =36 years. On the day of oocyte
      aspiration, consenting patients were randomized according to whether all embryos
      underwent the hatching procedure (hatched; n = 41) or all embryos remained
      unhatched (controls; n = 48). Patients in both groups were treated with
      methylprednisolone and doxycycline starting on the day of oocyte retrieval and
      continuing for 4 days. The hatching procedure was performed approximately 55 h
      after insemination on all potential embryos for transfer and employed the release
      of acidified acid Tyrode's medium against the zona pellucida to create an opening
      approximately 20 microm in diameter. No significant differences were noted in the
      mean age, number of oocytes aspirated and number of embryos transferred between
      the hatched and control groups. In addition, no significant differences were
      observed in the rates of implantation (11.1 versus 11.3%), clinical pregnancy
      (39.0 versus 41.7%) and ongoing pregnancy (29.3 versus 35.4%) between the hatched
      and control groups respectively. These results suggest that assisted hatching may
      have no significant impact on IVF success rates in the patient population
      studied.

PMID- 9557849
TI  - In-vitro fertilization and intracytoplasmic sperm injection in the treatment of
      infertility after testicular cancer.
AB  - Treatment of testicular cancer (TC) may cause infertility due to reduced sperm
      quality with or without an ejaculation problem. In cases of anejaculation or
      retrograde ejaculation, spermatozoa can be obtained by transrectal
      electroejaculation (TE) or testicular sperm extraction (TESE) and used for in
      vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). In this
      study, 15 out of 17 couples evaluated for infertility after TC, underwent a total
      of 21 treatment cycles, resulting in 18 embryo transfers. Spermatozoa were
      obtained by TE in 16 cycles, by masturbation in three cycles and by TESE in one.
      In one cycle no spermatozoa were found using TESE. Fertilization and cleavage was
      achieved by IVF in seven cycles and ICSI in 11 cycles; average fertilization
      rates of 57 and 55% respectively were observed. Twelve clinical pregnancies
      occurred, of which 11 have been delivered or are ongoing. The ongoing pregnancy
      rate was 57% per cycle. These results show that infertility after testicular
      cancer can be treated effectively with IVF and that ICSI even permits treatment
      of patients who have severe oligozoospermia.

PMID- 9557850
TI  - Chromosome analysis in human oocytes remaining unfertilized after in-vitro
      insemination: effect of maternal age and fertilization rate.
AB  - The incidence of chromosomal abnormalities was studied in 719 unfertilized human
      oocytes obtained from our in-vitro fertilization (IVF) programme. To make
      chromosome preparations, a gradual fixation/air-drying method was utilized. Of
      388 oocytes successfully karyotyped, 70 (18.0%) were abnormal. The abnormalities
      included 33 aneuploidies (8.5%) (14 hyperhaploidies and 19 hypohaploidies), 25
      diploidies (6.4%) and 15 structural abnormalities (3.9%), three of them being
      accompanied by aneuploidy. Of the 33 aneuploidies, 16 (48.5%) showed the loss or
      gain of dyads (so-called non-disjunction), while 17 (51.5%) showed the loss or
      gain of monads (so-called predivision). There was no maternal age-dependent
      increase in the incidence of aneuploidy. Unfertilized oocytes from patients with
      a high fertilization rate (>25%) had a significantly higher (11.4%, P < 0.05)
      incidence of diploidy compared with the oocytes from the remaining patients (4.3
      and 4.0%), suggesting that diploid oocytes might have a lower fertilizing
      ability.

PMID- 9557851
TI  - Fluorescent in-situ hybridization on human embryos showing cleavage arrest after
      freezing and thawing.
AB  - Our current freezing-thawing policy is to transfer only embryos that cleave
      further in the 24 h following thawing. The purpose of our study was to
      investigate the incidence of numerical abnormalities for chromosomes X, Y and 1
      in blastomeres of human preimplantation embryos that survived cryopreservation
      but did not cleave further after thawing. A total of 63 embryos surviving a
      freezing-thawing cycle but not cleaving further within 24 h after thawing were
      screened. Of the 63 screened embryos that showed cleavage arrest 24 h after
      thawing, 56 embryos (88.9%) remained arrested 48 h after thawing and slightly
      more than half of these (29/56; 51.8%) showed further deterioration in
      morphological quality. Seven embryos (11.1%) showed signs of further cleavage;
      five embryos showed additional cleavage of one blastomere and two developed a
      blastocoelic cavity. Fluorescent in-situ hybridization (FISH) with three specific
      probes for simultaneous detection of chromosomes X, Y and 1 was performed and was
      successful in 60 out of 63 embryos. Of these successfully labelled embryos, 26
      (43.3%) were in the diploid range: 12 (20%) were uniformly diploid for the
      chromosomes X, Y and 1; three embryos showed aneuploidy in all their blastomeres
      (two were XXY-karyotype and one was monosomy 1) and in 11 embryos nondisjunction
      was detected. Thirteen embryos were categorized as being either haploid,
      triploid, tetraploid or hexaploid. Nine embryos were classified as mosaic and 12
      as being highly abnormal or chaotic. These preliminary results suggest that a
      large proportion of embryos that do not cleave further after freezing and thawing
      carry chromosomal aberrations. This finding supports our policy of not
      transferring cryopreserved embryos which do not cleave further 24 h following
      thawing.

PMID- 9557852
TI  - An evaluation of propofol toxicity on mouse oocytes and preimplantation embryos.
AB  - Mouse biological assays were used to investigate potential adverse effects of
      propofol on the oocyte's competence to fuse with spermatozoa and on the embryo's
      ability to develop to the blastocyst stage. Cumulus-enclosed metaphase II oocytes
      were exposed for 1 h to 0.01, 0.1, 0.4, 1 and 10 microg/ml propofol (Diprivan)
      and subjected to a sperm-oocyte fusion test based on the dye (Hoechst 33342)
      transfer technique. Oocytes exposed to 0.4, 1 and 10 microg/ml propofol showed a
      significant reduction in the rate of sperm fusion and underwent pronuclei
      formation at a rate similar to that of sperm fusion. In a second trial, mouse 1
      cell and 2-cell embryos were exposed to varying propofol concentrations for 14h
      and then checked for subsequent development. Although adverse effects were not
      observed in 2-cell embryos, treatment of 1-cell embryos with propofol
      concentrations ranging from 0.01 to 10 microg/ml resulted in the inhibition of
      cleavage to blastocyst stage. We conclude that propofol can negatively influence
      fertilization in the mouse by impairing the oocyte's ability to fuse with
      spermatozoa, without interfering with the sperm-induced activation of the cell
      cycle. Moreover, we document the peculiar sensitivity to propofol of mouse 1-cell
      embryos as compared with 2-cell embryos.

PMID- 9557853
TI  - Induction of inducible nitric oxide synthase expression in human secretory
      endometrium.
AB  - The endometrial secretory phase is characterized by stromal oedema, a
      premenstrual increase in stromal macrophages and an increased cytokine production
      as menstruation approaches. Nitric oxide (NO) is a mediator of vasodilatation and
      cytotoxicity which is synthesized from L-arginine by NO synthases (NOS). These
      enzymes are either constitutively expressed or induced by lipopolysaccharides
      and/or cytokines. The presence and function of the inducible isoform of NOS
      (iNOS) in normal human endometrium has not been fully elucidated until recently.
      Frozen tissue sections taken from 22 women who underwent hysterectomy and
      adnexectomy for benign disease were immunostained with antibodies raised against
      the different NOS isoforms to investigate the presence of NOS in human
      endometrium. iNOS stained positive in the glandular epithelial cells of the
      secretory endometrium. Staining was either weak or absent in the proliferative
      and inactive endometrium, as well as in the oviduct and the glandular epithelium
      of the endocervix. The stroma remained uniformly negative. Immunoreactivity for
      endothelial constitutive NOS (eNOS) was confined exclusively to endothelial
      cells. Furthermore, epithelial cells from endometrium, oviduct and endocervix and
      all endothelial cells showed positive staining for reduced nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase, which is a histochemical marker for
      NOS activity. Reverse transcriptase polymerase chain reaction (RT-PCR) was
      performed in order to assess the presence of NOS mRNA. Abundant expression of
      iNOS mRNA was detected in the secretory phase endometrium only. The strong
      expression of inducible NO synthase in human secretory phase endometrium suggests
      that the increased production of NO, probably induced by cytokines, may be
      relevant to the process of menstruation.

PMID- 9557854
TI  - Human endometrial perfusion after tubal occlusion.
AB  - We examined variations in human endometrial microvascular perfusion across one
      menstrual cycle in women who had undergone tubal ligation and did not report
      unusual menstruation. Endometrial red blood cell flux was monitored by laser
      Doppler fluxmetry via a fibreoptic probe atraumatically inserted transvaginally
      into the uterus of each of 13 conscious volunteers. The observations obtained
      have been compared with those previously reported from a matched control group of
      women [B.J. Gannon et al., Hum. Reprod., 12, 132-139 (1997)]. Women who had
      undergone tubal occlusion for sterilization exhibited greater endometrial
      perfusion during menstruation (cycle days 0-5), at the time of ovulation (cycle
      days 13-16) and in the late secretory phase (cycle days 23-28) than occurred in
      controls. In addition, vasomotion in the study group was lower than that in
      controls in the early and late secretory phase (cycle days 17-22 and 23-28).
      Tubal occlusion appeared to alter endometrial perfusion. It is possible that the
      reported menstrual changes in women following tubal ligation are a consequence of
      altered endometrial perfusion; a possible causative relationship is discussed.

PMID- 9557855
TI  - The shape of the endometrium evaluated with three-dimensional ultrasound: an
      additional predictor of extrauterine pregnancy.
AB  - The objective of this prospective follow-up study was to evaluate the potential
      utility of three-dimensional (3D) ultrasound to differentiate intrauterine from
      extrauterine gestations. Fifty-four pregnancies with a gestational age <10 weeks
      and with an intrauterine gestational sac <5 mm in diameter formed the study
      group. The configuration of the endometrium in the frontal plane of the uterus
      was correlated to eventual pregnancy outcome. After exclusion of three patients
      with a poor 3D-image quality the endometrial shape was asymmetrical with regard
      to the median longitudinal axis of the uterus in 84% of intrauterine pregnancies,
      whereas the endometrium showed a symmetry in the frontal plane in 90% of
      extrauterine pregnancies (P = 0.0000001). Intrauterine fluid accumulation may
      distort the uterine cavity, thus being responsible for false-positive as well as
      false-negative results. The evaluation of the endometrial shape in the frontal
      plane appears to be a useful additional means to distinguish intrauterine from
      extrauterine pregnancies, especially when a gestational sac is not clearly
      demonstrated with conventional ultrasound.

PMID- 9557856
TI  - Immunology of human implantation: from the invertebrates' point of view.
AB  - Pregnancies in outbred mammals may be regarded as successfully developed
      homografts. One of the hypotheses that attempts to answer the enigma of why the
      fetus is not rejected (fetal-maternal relationships are based on reciprocal
      expressions of foreign transplantation antigens) claims for the existence of
      possible evolutionary links between invertebrate allorecognition and mammalian
      implantation, based on some cellular similarities. This essay further discusses
      the possible evolutionary perspectives between vertebrates and invertebrates
      alloimmunities from a different viewpoint. We discuss similarities between
      natural transplantation in colonial marine invertebrates, which are followed by
      chimerism and a state of tolerance, and two natural transplantation events in the
      mammalian systems which both have records for prolonged chimerism and tolerance:
      the phenomenon of dizygotic twin fusions and the situation of fetal cells
      implantation. Earlier comparative evolutionary perspectives are revisited.

PMID- 9557857
TI  - Maternal serum androgens in human pregnancy: early increases within the cycle of
      conception.
AB  - Previous studies have demonstrated elevations in testosterone and androstenedione
      initiated within the cycle of conception in pregnant non-human primates, and
      minimal data in the human support the same picture. In the present study we have
      investigated a group of patients scheduled for artificial insemination with
      regular menstrual cycles. For this study all patients provided blood samples at 5
      days after the luteinizing hormone (LH) surges and daily through the luteal phase
      and into early pregnancy (n = 12). Patients who did not become pregnant served as
      normal controls (n = 9). We have measured 17-hydroxyprogesterone (17-OHP) as a
      marker of luteal activity not obscured by progesterone within the cycle of
      conception and testosterone and androstenedione as the major androgens. There
      were no significant changes in testosterone and androstenedione in the non
      pregnant controls, but both testosterone and androstenedione were significantly
      elevated in the pregnant luteal phase, with the first increases occurring at 15
      and 14 days respectively after the LH surge. Three of 12 pregnant patients did
      not demonstrate a dramatic increase in either testosterone or androstenedione and
      when examined more carefully a corresponding lack of increase in 17-OHP in those
      same subjects indicated less than optimal luteal activity, suggesting that these
      androgens were products of the corpus luteum. In three subjects in which
      consecutive non-pregnant and pregnant cycles were followed there was a dramatic
      increase from the non-pregnant luteal phase to the pregnant luteal phase
      indicating that the more important observation may be the concentrations of
      androgens in the conceptive luteal phase compared to some baseline, either
      previous luteal phase or even follicular phase. We have also studied changes in
      dehydroepiandrosterone sulphate and found that there was no significant
      contribution to this increase in androgens in early conception. These studies
      demonstrate a significant increase in both testosterone and androstenedione
      presumably of ovarian, specifically luteal, origin and that adrenal androgen
      production is not a factor in these changes.

PMID- 9557858
TI  - Simultaneous bilateral tubal pregnancy following in-vitro fertilization and
      embryo transfer.
AB  - A case of simultaneous bilateral tubal pregnancy resulting from in-vitro
      fertilization and embryo transfer is presented. Repeated transvaginal ultrasound
      examinations confirmed an intrauterine sac but no fetus. A diagnosis of early
      missed abortion was incorrectly made and a curettage was performed. The
      pathological examination showed the presence of decidua and Arias-Stella
      phenomenon but no chorionic villi. Diagnostic laparoscopy and laparotomy
      performed 40 days after embryo transfer (eighth week of gestation), revealed
      bilateral tubal pregnancy. Bilateral salpingectomy was performed.

PMID- 9557859
TI  - A woman with three ectopic pregnancies after in-vitro fertilization and embryo
      transfer.
AB  - Although a higher incidence of ectopic pregnancy has been reported after in-vitro
      fertilization (IVF) and embryo transfer, three ectopic pregnancies in the same
      woman is very rare. A patient of 32 years underwent IVF-embryo transfer six times
      within 3 years. Three of four conceptions resulted in ectopic pregnancies. The
      first involved simultaneous intrauterine and left tubal pregnancy, the second was
      a right tubal pregnancy, and the third was a right interstitial pregnancy. In IVF
      embryo transfer, bilateral salpingectomy does not remove the risk of interstitial
      or cornual pregnancy.

PMID- 9557860
TI  - Fecundity in Thai and European regions: results based on waiting time to
      pregnancy.
AB  - Very little is known about the frequency of subfecundity in different cultures,
      ethnic groups and regions. To fill this gap, the European Study Group on
      Infertility and Subfecundity established data on the prevalence of infertility
      and subfecundity in five European regions. In this study, a comparison of
      fecundity was made between 4035 Caucasian women from five European countries and
      1496 Asian women from southern Thailand. Fecundity was measured using 'time to
      pregnancy', i.e. the time women took to conceive after stopping contraceptive
      methods. The Thai primigravid women had a shorter time to pregnancy than European
      women, whereas time to pregnancy was found to be longer among Thai multigravidae,
      although this was not statistically significant. This study has illustrated that
      cross-culture comparison of subfecundity is difficult despite using a common
      protocol and questionnaire because of differences in the use of contraceptive
      methods and a different concept of pregnancy planning. The distribution of time
      to pregnancy for the Thai women was not outside the variation found within the
      European samples.

PMID- 9557861
TI  - Recurrent miscarriage: principles of management.
AB  - Recurrent miscarriage is a heterogeneous condition which has many possible
      underlying causes. Ideally, couples with the problem should be managed in a
      dedicated miscarriage clinic, with thorough investigations according to a
      protocol, with structured history and investigation sheets. Counselling is an
      important feature and may be provided by a specially trained counsellor, or
      specialized nurse appropriately trained in counselling. Counselling should
      include an explanation of the possible underlying causes of the condition, and of
      the prognosis of each of the conditions. There is no definite cause of
      miscarriage in approximately half of the patients. No treatment is needed in this
      group, apart from reassurance and tender loving care. Treatment of unproven
      value, for example progesterone support in early pregnancy, should not be
      offered. Treatment offered empirically or as part of a research project should
      have a sound scientific and statistical basis, and should include careful
      counselling with informed consent of the patient. There are many controversial
      issues in the management of recurrent miscarriage; consequently, there is a need
      for locally agreed guidelines for management. Women who conceive again should be
      offered regular monitoring, including serial ultrasonography in the first
      trimester of pregnancy. An active audit programme to review regularly the various
      outcome measures set against defined targets should be established in the clinic.

PMID- 9557862
TI  - Obstetric and perinatal outcome after oocyte donation: comparison with in-vitro
      fertilization pregnancies.
AB  - The obstetric and perinatal outcome in 51 oocyte donation pregnancies (61
      infants) was compared with that of a control group of standard in-vitro
      fertilization (IVF) patients (97 pregnancies, 126 infants). The oocyte recipients
      (mean +/- SD age 33.5+/-4.7 years) included 39 women with ovarian failure and 12
      women with functioning ovaries. In oocyte recipients, first trimester bleeding
      (53%) occurred significantly more often than in IVF mothers (31%, P < 0.01).
      Pregnancy-induced hypertension was observed in 31% of oocyte recipients compared
      with 14% in IVF mothers (P < 0.05). There was no difference in the duration of
      pregnancies or in the preterm delivery rate between the two groups. When
      restricting analysis to singleton pregnancies, 63% of oocyte recipients were
      hospitalized in the antenatal period compared with 29% in the IVF group (P <
      0.001). The Caesarean section rate was 57% in the oocyte donation group and 37%
      in the IVF group (P < 0.05). Birthweight in singleton pregnancies was similar in
      both groups. The perinatal mortality rate was 3.3% in the oocyte donation group
      and 0% in the IVF group. In conclusion, oocyte donation pregnancies are
      associated with an increased risk compared with IVF pregnancies, but the
      complications are usually manageable and most oocyte recipients experience a good
      pregnancy outcome.

PMID- 9557863
TI  - Activated autologous blood therapy in recurrent spontaneous abortion--results of
      a pilot study.
AB  - This study was undertaken to investigate the influence of activated autologous
      blood therapy on immunological parameters and on the clinical outcome in patients
      with recurrent spontaneous abortion. In a prospective trial, 36 women with
      recurrent spontaneous abortion were treated with intramuscular reinjections of
      extracorporally haemolysed and ultraviolet irradiated autologous blood. A
      comprehensive immunological investigation revealed significant changes in
      lymphocyte subpopulations, plasma complement levels, mitogen stimulation and
      immunoglobulin levels during the treatment period. No side-effects were reported
      by the patients. From June 1994 to November 1995, 22 intrauterine and one
      extrauterine pregnancies occurred, resulting in 19 (86%) live births, two (9%)
      spontaneous abortions and one (4%) artificial abortion compared with a 64% live
      birth rate in the historical control group. We conclude that activated autologous
      blood therapy has detectable effects on the immune system, and seems to be
      promising for further investigation concerning the treatment of idiopathic
      recurrent spontaneous abortion.

PMID- 9557864
TI  - Term delivery in a woman with severe congenital neutropenia, treated with growth
      colony stimulating factor.
AB  - The patient was diagnosed in childhood as having severe congenital neutropenia
      and had recurrent admissions with severe infections. In 1987, prior to getting
      married, she was sterilized. She continued to require i.v. antibiotics when she
      contracted a severe infection. On one occasion, she was treated with growth
      colony stimulating factor (G-CSF). Her increased neutrophil count was sustained
      following this treatment. In June 1993, she wished to start a family and
      underwent in-vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte
      retrieval. She conceived on her first cycle and an ultrasound scan revealed a
      singleton pregnancy. Throughout the course of the pregnancy, her white cell count
      was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed
      uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At
      38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean
      section. His white cell count was normal. This is the first case of G-CSF being
      used before conception and during pregnancy in a patient with congenital
      neutropenia. It shows that advances in cytokine therapy and close
      interdisciplinary liaison can lead to a successful outcome and help patients, who
      would otherwise remain childless, to achieve a family.

PMID- 9557866
TI  - Reply to Rinkevitch: Immunology of human implantation: from the invertebrate's
      point of view.

PMID- 9557865
TI  - Gamete donation guidelines. The Corsendonk consensus document for the European
      Union.

PMID- 9557867
TI  - Is colour Doppler useful in the diagnosis of functional ovarian cysts?

PMID- 9557868
TI  - Time to rethink the indiscriminate use of testicular biopsy for sperm retrieval?

PMID- 9557869
TI  - Glycans of higher plant peroxidases: recent observations and future speculations.
AB  - Plant peroxidases are composed of a peptide and associated heme, calcium and
      glycans. The 3D structure of the major cationic peanut peroxidase has revealed
      the sites of the heme and calcium. But the diffraction of the glycans was not
      sufficient to show their structure. This review presents research that has been
      executed to obtain putative glycans and their binding sites, and to gain an
      indirect insight into these glycans. It also offers approaches that will be used
      to determine the function of the glycans on the peanut peroxidase. Some
      comparisons are made with other plant glycoproteins including peroxidases from
      plants other than peanut.

PMID- 9557870
TI  - Three-dimensional structure of a glycosphingolipid having a novel carbohydrate
      linkage, Galbeta1-4(Fucalpha1-3)Glcbeta1-3Galbeta, determined by theoretical
      calculations.
AB  - The novel glycosphingolipid, SEGLx (Galbeta1-4(Fucalpha1-3)Glcbeta1-3GalbetaCer),
      which was identified by us (Kawakami Y, et al. (1993) J Biochem 114: 677-83),
      shows a characteristic spectrum on 1H-NMR analysis, in which the anomeric proton
      resonances of a reducing end galactose and a glucose are split. To elucidate the
      structural characteristics of SEGLx, we determined its three-dimensional (3D)
      structure by means of computer simulation, involving such techniques as molecular
      mechanics (MM2), the semiempirical molecular orbital method (AM1), molecular
      dynamics (Amber), and computer 3D modelling. With the hypothesis that all OH
      group(s) of a ceramide participate in intramolecular hydrogen bonds, two kinds of
      stable conformers, horizontal and right-angled ones, were formed, depending on
      the ceramide species. The present findings suggest that the chemical species of
      both the long chain base and fatty acid moieties, mainly the occurrence of OH
      group(s), affect the chemical shifts of the anomeric proton resonances not only
      of the reducing terminal galactose but also the penultimate glucose through the
      formation of intramolecular hydrogen bonds. Computer simulation through
      theoretical calculation and 3D modelling was shown to be the best means of
      confirming the results obtained by experimental analysis.

PMID- 9557872
TI  - High temperature conjugation of proteins with carbohydrates.
AB  - A new procedure was used to conjugate lactose and dextran with BSA without using
      coupling or activating reagents. The method is simple, rapid and cheap. Reducing
      sugars covalently bind to proteins when lyophilized together and briefly heated
      to a high temperature.

PMID- 9557874
TI  - Expression, purification, and biochemical characterization of a recombinant
      lectin of Sarcocystis muris (Apicomplexa) cyst merozoites.
AB  - The mature major microneme protein of Sarcocystis muris cyst merozoites, which is
      known as a dimeric lectin with high affinity to galactose and some of its
      derivatives, was expressed in Escherichia colias a histidine-tagged fusion
      protein. The recombinant polypeptide, which was recognized by a monoclonal
      antibody directed against the native lectin, was purified from inclusion bodies
      after solubilization and refolding, using a combination of metal chelate and
      lactose affinity chromatography. The apparent molecular mass of the refolded
      polypeptide as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoreses was 16 kDa, whereas gel filtration chromatography clearly
      demonstrated that the recombinant protein, like its native counterpart, exists as
      a homodimer of two non-covalently associated subunits. Inhibition of
      haemagglutination suggests that the combining site of the recombinant lectin
      recognizes N-acetyl-galactosamine as the dominant sugar, thus confirming the
      correct folding of the monosaccharide combining site in the renatured lectin. To
      the best of our knowledge, this work represents the first reported detailed
      characterization of a recombinant lectin from apicomplexan parasites, and may
      contribute to a better understanding of the process of host cell recognition and
      invasion by these obligate intracellular protozoa.

PMID- 9557873
TI  - Combined preparative enzymatic synthesis of dTDP-6-deoxy-4-keto-D-glucose from
      dTDP and sucrose.
AB  - dTDP-6-deoxy-4-keto-D-glucose (1), the common intermediate in the biosyntheses of
      the manifold deoxysugars, was synthesized on a gram-scale by the combination of
      sucrose synthase and dTDP-D-glucose 4,6-dehydratase in a fed batch, starting the
      reaction with dTDP. This process allowed a dTDP conversion with a 100% rate. An
      easy and efficient three-step purification with anion-exchange chromatography and
      gel filtration gave 1.1 g of 1 in an overall yield of 73%. This work realizes a
      first step for an economic access to activated deoxysugars.

PMID- 9557875
TI  - Purification and properties of recombinant beta-galactosidase from Bacillus
      circulans.
AB  - A gene encoding beta-galactosidase from Bacillus circulans which had hydrolysis
      specificity for the beta1-3 linkage was expressed in Escherichia coli. The beta
      galactosidase was purified from crude cell lysates of E. coli by column
      chromatographies on Resource Q and Sephacryl S-200 HR. The enzyme released
      galactose with high selectivity from oligosaccharides which had terminal beta1-3
      linked galactose residues. However it did not hydrolyse beta1-4 linked
      galactooligosaccharides. Moreover, Galbeta1-3GlcNAc, Galbeta1-3GalNAc, and their
      p-nitrophenyl glycosides were regioselectively synthesized in 10-46% yield by the
      transglycosylation reaction using this enzyme.

PMID- 9557876
TI  - T lymphocyte activation results in an increased expression of beta-1,4
      galactosyltransferase: phorbol ester induces a similar enhancement in the absence
      of mitosis.
AB  - We previously showed that in vitro activated human T lymphocytes expressed
      increased amounts of beta-1,6-branched N-linked oligosaccharides (Lemaire S etal.
      (1994) J Biol Chem269: 8069-74), which have been proposed to participate in the
      regulation of the immune process. In the present paper, we compared the activity
      and expression of beta-1,4-galactosyltransferase (GalT), one of the
      glycosyltransferases involved in the biosynthesis of these beta-1,6-branched N
      linked oligosaccharides, before and after in vitro activation of T lymphocytes
      after a 40h treatment with a mixture of phorbol 12-myristate 13-acetate and
      Phaseolus vulgaris lectin. After treatment, the enzymatic activity of the GalT
      was significantly increased and immunoblot experiments performed with a
      monoclonal antibody to human GalT showed an increased intensity of the GalT band
      at 49 kDa, attributable to an enhancement of GalT mRNA level, as shown by
      Northern blots. However, treatment of the same T-lymphocytes by phorbol ester
      alone, which is unable to induce mitosis, resulted in a comparable increase of
      the expression of GalT. Moreover, these phorbol ester-treated T lymphocytes,
      analysed by flow cytometry exhibited a two-fold increase in the expression of
      GalT. Finally, confocal fluorescence microscopy performed on all T lymphocytes
      (treated or not) showed that the flow cytometric signal of GalT originates from
      intracellular, Golgi-associated antigen only since no surface GalT was detected.

PMID- 9557871
TI  - NetOglyc: prediction of mucin type O-glycosylation sites based on sequence
      context and surface accessibility.
AB  - The specificities of the UDP-GalNAc:polypeptide Nacetylgalactosaminyltransferases
      which link the carbohydrate GalNAc to the side-chain of certain serine and
      threonine residues in mucin type glycoproteins, are presently unknown. The
      specificity seems to be modulated by sequence context, secondary structure and
      surface accessibility. The sequence context of glycosylated threonines was found
      to differ from that of serine, and the sites were found to cluster. Non-clustered
      sites had a sequence context different from that of clustered sites. Charged
      residues were disfavoured at position -1 and +3. A jury of artificial neural
      networks was trained to recognize the sequence context and surface accessibility
      of 299 known and verified mucin type O-glycosylation sites extracted from O
      GLYCBASE. The cross-validated NetOglyc network system correctly found 83% of the
      glycosylated and 90% of the non-glycosylated serine and threonine residues in
      independent test sets, thus proving more accurate than matrix statistics and
      vector projection methods. Predictions of O-glycosylation sites in the envelope
      glycoprotein gp120 from the primate lentiviruses HIV-1, HIV-2 and SIV are
      presented. The most conserved O-glycosylation signals in these evolutionary
      related glycoproteins were found in their first hypervariable loop, V1. However,
      the strain variation for HIV-1 gp120 was significant. A computer server,
      available through WWW or E-mail, has been developed for prediction of mucin type
      O-glycosylation sites in proteins based on the amino acid sequence. The server
      addresses are http://www.cbs.dtu.dk/services/NetOGlyc/ and netOglyc@cbs.dtu.dk.

PMID- 9557877
TI  - Studies on the interaction between hyaluronan and a rat colon cancer cell line.
AB  - Binding studies with 125I-Tyr labelled hyaluronan (HA) on a cultured rat colon
      cancer cell line were performed to characterize the association of HA to tumour
      cells in vitro. Results show a specific and saturable binding (Kd=1.36 nM) which
      indicates the presence of an HA binding receptor on the tumour cells. There is a
      specific constant increase of cell-associated HA over time, which indicates that
      HA is specifically taken up by the cells through endocytosis. The binding of 125I
      Tyr labelled HA was more effectively inhibited by unlabelled HA of high MW in
      relation to low MW species of the polysaccharide indicating that the receptor
      binds HA of high MW with greater affinity than low MW species. In competition
      experiments, the HA-binding could not be inhibited by other polysaccharides such
      as chondroitin sulphate and heparin. Nor could ligands for scavenger receptors
      and antibodies directed towards ICAM-1, CD 44 and RHAMM (Receptor for HA Mediated
      Motility) significantly inhibit the association of HA to tumour cells.

PMID- 9557878
TI  - Inflammation-induced expression of sialyl LewisX is not restricted to alpha1-acid
      glycoprotein but also occurs to a lesser extent on alpha1-antichymotrypsin and
      haptoglobin.
AB  - Acute and chronic inflammation-induced expression of sialyl LewisX has already
      been shown to occur on alpha1-acid glycoprotein. We now demonstrate that this
      phenomenon is not restricted to alpha1-acid glycoprotein but also occurs on two
      other acute-phase proteins. ie on alpha1-antichymotrypsin and on haptoglobin. The
      level of expression of sialyl LewisX on these proteins was lower than on alpha1
      acid glycoprotein, in all likelihood because alpha1-acid glycoprotein is the only
      acute-phase protein containing tetraantennary glycans. No expression of sialyl
      LewisX was detectable on alpha1-protease inhibitor, a protein with a high
      diantennary glycan content. Non-sialylated LewisX was not detectable on these
      major acute-phase proteins in any of the conditions studied. This indicates that
      the majority of the a3-linked fucose residues are present as sialyl LewisX on
      alpha1-acid glycoprotein, alpha1-antichymotrypsin and haptoglobin. The absolute
      contribution to the total phenotype in plasma of protein containing this
      determinant in a multivalent form was highest for alpha1-acid glycoprotein. This
      leads us to propose that alpha1-acid glycoprotein is, among the acute-phase
      proteins studied, the one with the highest potential for interference with the
      extravasation of leukocytes by binding to the selectins.

PMID- 9557879
TI  - MMC and LD simulations of alpha-D-Manp-(1-->2)-beta-D-Glcp-OMe: comparison to
      long-range heteronuclear NMR coupling constants and to the crystal structure.
AB  - The conformational flexibility and the dynamics of alpha-D-Manp(1-->2)-beta-D
      Glcp-OMe have been investigated by Metropolis Monte Carlo (MMC) and Langevin
      dynamics (LD) simulations. The two simulation techniques employ different force
      fields, namely the HSEA force field and a CHARMm-based force field. The former
      shows less conformational flexibility than the latter, in which a multiple energy
      minima conformational space is sampled. Long-range heteronuclear nuclear magnetic
      resonance (NMR) coupling constants have been measured by selective excitations of
      the carbons at the glycosidic linkage. Calculated 3J(C,H) values from MMC and LD
      simulations show excellent agreement to those from NMR experiments. The X-ray
      crystal structure has a conformation within a region of the conformational space
      populated in both force fields.

PMID- 9557880
TI  - Studies on the conformational behaviour of GlcNAc-Man3-GlcNAc2 oligosaccharides
      using molecular dynamics simulations.
AB  - Three-dimensional structures of the natural substrate unit for the enzyme N
      acetylglucosamine-transferase II, GIcNAc-Man3-GlcNAc2, were investigated by
      molecular modelling methods. Molecular dynamics (MD) and molecular mechanics
      calculations on two hexasaccharides, namely GlcNAc-Man3-GlcNAc2-Asn and GlcNAc
      Man3-GlcNAc2-OMe were performed by the Biosym/MSI software using the CVFF and
      CFF95 force fields in vacuum. The MD simulations were calculated for 3 ns at
      different simulation temperatures and for two values of dielectric constant,
      epsilon=1 and epsilon=4. From each 3 ns trajectory, 3050 structures have been
      optimized. The local minima obtained have been clustered into families exhibiting
      similar values of glycosidic torsional angles phi, psi, and omega. The influence
      of the simulation conditions and force fields used on the conformational
      behaviour and structure of the title oligosaccharides is discussed.

PMID- 9557881
TI  - Removal of 106 amino acids from the N-terminus of UDP-GlcNAc: alpha-3-D-mannoside
      beta-1,2-N-acetylglucosaminyltransferase I does not inactivate the enzyme.
AB  - UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnTI,
      EC 2.4.1.101) plays an essential role in the conversion of oligomannose to
      complex and hybrid N-glycans. Rabbit GnTI is 447 residues long and has a short
      four-residue N-terminal cytoplasmic tail, a 25-residue putative signal-anchor
      hydrophobic domain, a stem region of undetermined length and a large C-terminal
      catalytic domain, a structure typical of all glycosyltransferases cloned to date.
      Comparison of the amino acid sequences for human, rabbit, mouse, rat, chicken,
      frog and Caenorhabditis elegans GnTI was used to obtain a secondary structure
      prediction for the enzyme which suggested that the location of the junction
      between the stem and the catalytic domain was at about residue 106. To test this
      hypothesis, several hybrid constructs containing GnT I with N- and C-terminal
      truncations fused to a mellitin signal sequence were inserted into the genome of
      Autographa californica nuclear polyhedrosis virus (AcMNPV), Sf9 insect cells were
      infected with the recombinant baculovirus and supernatants were assayed for GnTI
      activity. Removal of 29, 84 and 106 N-terminal amino acids had no effect on GnTI
      activity; however, removal of a further 14 amino acids resulted in complete loss
      of activity. Western blot analysis showed strong protein bands for all truncated
      enzymes except for the construct lacking 120 N-terminal residues indicating
      proteolysis or defective expression or secretion of this protein. The data
      indicate that the stem is at least 77 residues long.

PMID- 9557882
TI  - The generation and characterization of a rat neural cell line overexpressing the
      alpha2,6(N) sialyltransferase.
AB  - In order to examine the effects of altered protein sialylation on neural cell
      function, B104 rat neuroblastoma cells were stably transfected with the cDNA
      coding for alpha2,6(N) sialyltransferase (ST(6)N). Lectin blot analysis of the
      clones demonstrated an increase in staining of the Sambucus nigra lectin, which
      detects alpha2,6 linked sialic acid, in parallel with enzyme activity. There was
      a concomitant decrease in staining by the Maackia amurensis lectin which labels
      alpha2,3-linked sialic acid, indicating that the individual sialyltransferase
      enzymes may compete for penultimate galactose acceptor sites. While there was an
      initial increase in protein-bound sialic acid in parallel with enzyme activity,
      the sialylation of the cells was demonstrated to be saturable. There was an
      inverse relationship between cell adhesion to a fibronectin substrate and ST(6)N
      activity suggesting that the negatively charged sugar acts to modulate cell
      substrate interaction. These cells will provide an ideal model system with which
      to further investigate the effect of altered sialic acid on neural cell function.

PMID- 9557884
TI  - Previously undescribed spondyloepiphyseal dysplasia associated with
      craniosynostosis, cataracts, cleft palate, and mental retardation: report of four
      sibs.
AB  - We report on four Japanese sibs (three brothers and one sister) with a previously
      unreported syndrome of spondyloepiphyseal dysplasia, craniosynostosis, cataracts,
      cleft palate, and mental retardation. Most clinical manifestations were evident
      neonatally, but skeletal changes and cataracts became substantial in early
      childhood. Radiological anomalies comprised coronal synostosis, mild epiphyseal
      dysplasia, particularly in the distal tibiae, strikingly delayed patellar
      ossification, mild metaphyseal splaying, hypoplastic ilia with iliac flare, and
      platyspondyly with ovoid-shaped or posteriorly humped vertebral bodies. The
      nonconsanguineous parents were mildly mentally retarded, and sibs of both gender
      were equally affected; thus, inheritance was likely autosomal recessive.

PMID- 9557883
TI  - Concanavalin A binding and endoglycosidase D resistance of beta1,2-xylosylated
      and alpha1,3-fucosylated plant and insect oligosaccharides.
AB  - The binding to concanavalin A (Con A) by pyridylaminated oligosaccharides derived
      from bromelain (Manalpha1,6(Xylbeta1,2) Manbeta1,
      4GlcNAcbeta1,4(Fucalpha1,3)GlcNAc), horseradish peroxidase
      (Manalpha1,6(Manalpha1,3) (Xylbeta1,2)Manbeta1, 4GlcNAcbeta1,4(Fucalpha1,3)
      GlcNAc), bee venom phospholipase A2 (Manalpha1,6Manbeta1,4GlcNAcbeta1,4GlcNAc and
      Manalpha1,6(Manalpha1,3)Manbeta1,4GlcNAcbeta1,4 (Fucalpha1,3)GlcNAc) and zucchini
      ascorbate oxidase (Manalpha1,6(Manalpha1,3) (Xylbeta1,2)Manbeta1,4
      GlcNAcbeta1,4GlcNAc) was compared to the binding by Man3GlcNAc2, Man5GlcNAc2 and
      the asialo-triantennary complex oligosaccharide from bovine fetuin. While the
      fetuin oligosaccharide did not bind, bromelain, zucchini, Man2GlcNAc2 and
      horseradish peroxidase were retarded (in that order). The alpha1,3-fucosylated
      phospholipase, Man3GlcNAc2 and Man5GlcNAc2 structures were eluted with 15 mM
      alpha-methylmannoside. It is concluded that core alpha1,3-fucosylation has little
      or no effect on ConA binding while xylosylation decreases affinity for ConA. In a
      parallel study comparing the endoglycosidase D (Endo D) sensitivities of
      Man3GlcNAc2, IgG-derived GlcNAcbeta1,
      2Manalpha1,6(GlcNAcbeta1,2Manalpha1,3)Manbeta1,+
      ++4GlcNAcbeta1,4(Fucalpha1,6)GlcNAc, the phospholipase Manalpha1,6(Manalpha1,3)
      Manbeta1, 4GlcNAcbeta1,4(Fucalpha1,3)GlcNAc, and horseradish and zucchini
      pyridylaminated N-linked oligosaccharides, it was found that only the Man3GlcNAc2
      structure was cleaved. The IgG structure was sensitive only when beta
      hexosaminidase was also present. Thus, in contrast to core alpha1,6-fucosylated
      structures, such as those present in mammals, the presence of core alpha1,3
      fucose, as found in structures from plants and insects, and/or beta1,2-xylose, as
      found in plants, causes resistance to Endo D.

PMID- 9557885
TI  - Prevalence of 22q11 region deletions in patients with velopharyngeal
      insufficiency.
AB  - Velo-cardio-facial syndrome, DiGeorge syndrome, conotruncal anomaly face
      syndrome, tetralogy of Fallot, and pulmonary atresia with ventricular septal
      defect are all associated with hemizygosity of 22q11. While the prevalence of the
      deletions in these phenotypes has been studied, the frequency of deletions in
      patients presenting with velopharyngeal insufficiency (VPI) is unknown. We
      performed fluorescence in situ hybridization for locus D22S75 within the 22q11
      region on 23 patients with VPI (age range 5-42 years) followed in the
      Craniofacial Clinic at the University of Florida. The VPI occurred either as a
      condition of unknown cause (n=16) or as a condition remaining following primary
      cleft palate surgery (n=7). Six of sixteen patients with VPI of unknown cause and
      one of seven with VPI following surgery had a deletion in the region. This study
      documents a high frequency of 22q11 deletions in those presenting with VPI
      unrelated to overt cleft palate surgery and suggests that deletion testing should
      be considered in patients with VPI.

PMID- 9557886
TI  - Three new cases of spondylocarpotarsal synostosis syndrome: clinical and
      radiographic studies.
AB  - Spondylocarpotarsal synostosis syndrome (SSS) or congenital synspondylism is a
      recently delineated clinical entity. At least 15 patients have been reported. We
      present 3 new patients, 2 of whom were sibs born to first-cousin parents. All of
      our patients had multiple synostoses involving cervical, thoracic and/or lumbar
      vertebral bodies and carpal/tarsal bones, scoliosis/lordosis, and short stature.
      Sensorineural deafness was found in 2 of the 3 patients. Analysis of clinical
      manifestations suggests clinical variability and genetic heterogeneity in SSS. Of
      a total of 18 SSS patients, 10 were five pairs of sibs from five families, with
      first-cousin consanguinity of parents in 3, indicating that at least one type of
      SS is an autosomal-recessive disorder.

PMID- 9557888
TI  - Characterization of a supernumerary marker derived from chromosome 17 by
      microdissection in an adult with MR/MCA.
AB  - We describe a 38-year-old adult who has a supernumerary marker chromosome in 40%
      of metaphase cells which was identified by reverse in situ hybridization with a
      DNA probe made by microdissection to be derived from chromosome 17. The
      breakpoints are estimated by G-banding and fluorescence in situ hybridization
      (FISH) to consist of the region from 17p11.1 to proximal 17q21. The propositus
      displayed severe growth retardation, kyphoscoliosis, bilateral cataracts, severe
      calcaneovalgus deformity of the feet, dysmorphic facies, profound mental
      retardation, and multiple medical problems requiring ongoing medical management.
      These problems included a mitral valve prolapse with regurgitation, recurrent
      upper and lower respiratory tract infections, and severe respiratory
      insufficiency. The relatively long survival of this patient enabled us to
      describe the natural history of this rare chromosomal mutation.

PMID- 9557887
TI  - Further delineation of a new (Van Den Ende-Gupta) syndrome of blepharophimosis
      contractural arachnodactyly, and characteristic face.
AB  - We report on 2 unrelated Indian girls with blepharophimosis, arachnodactyly,
      digital contractures which improved spontaneously, elbow deformity, beaked nose,
      everted lips, and large ears, findings similar to those in 2 cases reported
      previously by Van Den Ende et al. [1992, Am J Med Genet 42:467-469] and Gupta et
      al. [1995, J Med Genet 32:809-812], thus delineating a new syndrome of
      contractural arachnodactyly with characteristic facial anomalies.

PMID- 9557889
TI  - Smith-Magenis syndrome resulting from a de novo direct insertion of proximal 17q
      into 17p11.2.
AB  - We report on a de novo intrachromosomal rearrangement of chromosome 17 in a
      patient with Smith-Magenis syndrome (SMS). This 11-year-old boy had short
      stature, midfacial hypoplasia, and behavioral problems characteristic of this
      syndrome. Cytogenetic analysis showed that the proximal long arm of a chromosome
      17 (q11.2-q21.3) was inserted into its short arm at p11.2, resulting in an
      apparent deletion of the SMS critical region [ins(17)(p11.2q11.2q21.3)].
      Fluorescence in situ hybridization studies (FISH) demonstrated that the inserted
      segment included both the ERBB2 and RARA loci, and dual color hybridizations
      defined the insertion as direct, with ERBB2 located more proximally on the short
      arm of the der(17). The resulting deletion of the short arm included loci c130G3,
      D17S258, FLI, and D17S29, while the more proximal loci, D17S446 and D17S58,
      remained apparently unaffected and in their native locations. The CMT1A locus
      also remained in its native location on the short arm of the metacentric der(17)
      chromosome. A de novo intrachromosomal insertional rearrangement of chromosome 17
      in a case of SMS has not been reported previously and further illustrates the
      instability of this chromosomal region.

PMID- 9557890
TI  - Camptodactyly, myopia, and fibrosis of the medial rectus of the eye in two sibs
      born to consanguineous parents: autosomal recessive entity?
AB  - Unaffected but consanguineous parents suggest autosomal recessive inheritance of
      a previously apparently undescribed syndrome of camptodactyly, fibrosis of the
      medial rectus muscle of the eye, severe myopia, facial anomalies, joint
      contractures, and mild scoliosis in a 13-year-old Turkish girl and her 11-year
      old brother. The girl also had ptosis.

PMID- 9557891
TI  - Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos
      National Foundation (USA) and Ehlers-Danlos Support Group (UK).
AB  - Categorization of the Ehlers-Danlos syndromes began in the late 1960s and was
      formalized in the Berlin nosology. Over time, it became apparent that the
      diagnostic criteria established and published in 1988 did not discriminate
      adequately between the different types of Ehlers-Danlos syndromes or between
      Ehlers-Danlos syndromes and other phenotypically related conditions. In addition,
      elucidation of the molecular basis of several Ehlers-Danlos syndromes has added a
      new dimension to the characterization of this group of disorders. We propose a
      revision of the classification of the Ehlers-Danlos syndromes based primarily on
      the cause of each type. Major and minor diagnostic criteria have been defined for
      each type and complemented whenever possible with laboratory findings. This
      simplified classification will facilitate an accurate diagnosis of the Ehlers
      Danlos syndromes and contribute to the delineation of phenotypically related
      disorders.

PMID- 9557892
TI  - Neuropathologic findings in a case of OFDS type VI (Varadi syndrome).
AB  - Oral-facial-digital syndrome type VI (OFDS VI) or Varadi syndrome is a rare
      autosomal-recessive disorder distinguished from other oral-facial-digital
      syndromes by metacarpal abnormalities with central polydactyly and by cerebellar
      abnormalities. Histopathologic characterization of the cerebellar abnormalities
      has not been described previously. We describe the neuropathologic findings in a
      stillborn, 21-week estimated gestational age (EGA) male fetus diagnosed
      antenatally with signs of OFDS VI. Autopsy findings included: facial
      abnormalities, postaxial central polydactyly of the right hand, bilateral bifid
      toes, and absence of cerebellar vermis with hypoplasia of the hemispheric cortex.
      Microscopic analysis of the cerebellum demonstrated absence of the subpial
      granular cell layer and disruption or dysgenesis of the glial architecture. These
      histopathologic findings suggest that a primary neuronal or glial cell defect,
      rather than an associated Dandy-Walker malformation, may account for the
      cerebellar abnormalities in this form of oral-facial-digital syndrome.

PMID- 9557893
TI  - Retinal changes and tumorigenesis in Ramon syndrome: follow-up of a Brazilian
      family.
AB  - We report on the clinical evolution of the Brazilian family with Ramon syndrome
      described by de Pina-Neto et al. [1986, Am J Med Genet 25:441-443]. Three members
      (patients IV-2, IV-18, and IV-19) have developed pigmentary changes in the retina
      and paleness of the optic disk. Patient IV-18 also has developed giant
      hypertrophy of the labia minora that, when examined histopathologically, was
      found to be due to neoplastic fibroblast and epithelial proliferation caused by a
      fibromatous process similar to that reported in the gingivae of the patients with
      this syndrome. Audiologic function of patient IV-2 was normal, and no skin
      lesions were detected. The articular signs and symptoms show that the affected
      relatives developed rheumatoid arthritis, which is currently inactive in patient
      IV-18, whereas patient IV-2 did not develop these alterations.

PMID- 9557894
TI  - Heterogeneity in hereditary pancreatitis.
AB  - Hereditary pancreatitis (HP) is the most common form of chronic relapsing
      pancreatitis in childhood, and may account for approximately 25% of adult cases
      with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H)
      mutation within the cationic trypsinogen gene was found in 5/5 families studied
      with HP. In this study we report on the results of linkage and direct mutational
      analysis for the common R117H mutation examined in 8 nonrelated families with
      hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676,
      done initially in 4 families, yielded lod scores that were positive in 2,
      negative in one, and weakly positive in one. Direct mutational analysis of exon 3
      of the cationic trypsinogen gene in 6 families showed that all symptomatic
      individuals tested were heterozygous for the R117H mutation. Also, several
      asymptomatic but at-risk relatives were found to be heterozygous for this
      mutation. Affected individuals in the remaining 2 families did not have the
      mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the
      trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8
      cR proximal the dinucleotide repeat marker D7S676. The negative linkage and
      absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity
      in HP. Analysis of the R117H mutation is useful in identifying presymptomatic "at
      risk" relatives and in genetic counseling. Also, it can be useful in identifying
      children and adults with isolated chronic idiopathic pancreatitis.

PMID- 9557895
TI  - Genetic counseling in Angelman syndrome: the challenges of multiple causes.
AB  - The causal heterogeneity of Angelman syndrome (AS) makes providing information
      regarding recurrence risk both important and challenging, and may have a dramatic
      impact on reproductive decision-making for the nuclear and extended family. Most
      cases of AS result from typical large de novo deletions of 15q11-q13, and are
      expected to have a low (<1%) risk of recurrence. AS due to paternal uniparental
      disomy (UPD), which occurs in the absence of a parental translocation, is
      likewise expected to have a <1% risk of recurrence. Parental transmission of a
      structurally or functionally unbalanced chromosome complement can lead to 15q11
      q13 deletions or to UPD and will result in case-specific recurrence risks. In
      instances where there is no identifiable large deletion or UPD, the risk for
      recurrence may be as high as 50% as the result of either a maternally inherited
      imprinting center (IC) mutation or a ubiquitin-protein ligase (UBE3A) gene
      mutation. Individuals with AS who have none of the above abnormalities comprise a
      significant proportion of cases, and some may be at a 50% recurrence risk.
      Misdiagnoses, as well, can be represented in this group. In light of the many
      conditions which are clinically similar to AS, it is essential to address the
      possibility of diagnostic uncertainty and potential misdiagnosis prior to the
      provision of genetic counseling. Summaries of the different causal classes of AS
      as an algorithm for determination of recurrence risks are presented.

PMID- 9557896
TI  - Terminal deletion of the long arm of chromosome 10: a new case with breakpoint in
      q25.3.
AB  - Since the first patient with partial deletion of the long arm of chromosome 10
      was described in 1978, another 23 cases have been reported, with the breakpoint
      ranging from 10q23.3-26.2. To contribute further to the delineation of the
      monosomy 10qter syndrome, we describe a female child who, at age 3 6/12 years,
      was diagnosed with a de novo deletion of the long arm of chromosome 10, with a
      breakpoint in 10q25.3. The phenotypic manifestations in this child are compatible
      with those of previously reported cases. However, in contrast to most other
      patients, we found a moderate expression of the syndrome, with no genitourinary
      or cardiac malformations and with only mild retardation. Based on our
      observations and those of others, we conclude that a typical craniofacial
      appearance and varying degrees of psychomotor retardation are always found in
      patients with 10q- syndrome.

PMID- 9557897
TI  - Lethal syndrome of skeletal dysplasia and progressive central nervous system
      degeneration.
AB  - We describe 3 sibs (2 males and 1 female) with multiple congenital anomalies,
      poor growth, seizures, and progressive central nervous system (CNS) degeneration
      leading to death in infancy. Radiographic changes in all 3 were similar, and
      included moderate shortness of long bones, platyspondyly, and hypoplastic pelvis.
      Autopsies showed diffuse encephalomyelopathy and enlargement of the lateral and
      third ventricles. Lysosomal enzyme activities were normal. Collagen type II
      analysis on 2 of the sibs indicated normal collagen. Chromosomes appeared normal.
      Even though the radiographic and chondroosseous morphologic findings in these
      sibs have a certain similarity to Dyggve-Melchior-Clausen syndrome, their
      clinical course does not fit this condition. These infants appear to represent a
      new syndrome of bone dysplasia and CNS degeneration inherited as an autosomal
      recessive trait.

PMID- 9557898
TI  - Dilemma of trisomy 20 mosaicism detected prenatally: is it an innocent finding?
AB  - The clinical significance of mosaicism trisomy 20 detected prenatally following
      amniocentesis remains uncertain, due to the rarity of liveborn cases with
      inconsistent clinical findings, the short postnatal follow-up, and failure in
      evaluating other fetal tissues for the presence of the trisomy. We report on a 15
      month-old 46,XX chromosome constitution in white blood cells, while skin
      fibroblasts demonstrated trisomy 20 mosaicism (54%) by fluorescence in situ
      hybridization (FISH) analysis. Clinical examination of the baby showed only minor
      phenotypic signs (bilateral epicanthal folds, delayed closure of fontanel with no
      other gross anomalies), but demonstrated a considerable developmental delay in
      gross and fine motor skills along with hypotonicity. This is the second oldest
      described liveborn with trisomy 20 mosaicism confirmed in skin fibroblasts. This
      cytogenetic aberration along with her developmental delay suggests that the two
      findings are related and that aberration affects various fetal tissues and is not
      confined to extra-embryonic tissue as suggested previously. Yet, an undiagnosed
      condition may be the cause of the child's developmental delay. Based on this case
      and following a review of the literature we suggest that when mosaic trisomy 20
      is identified in amniocytes, further evaluation is required. Cord blood should be
      analyzed preferably by FISH. During counseling the parents should be advised of
      an additional risk, such as developmental delay, even when fetal cord karyotype
      and detailed ultrasonic scan are normal.

PMID- 9557899
TI  - Supernumerary nipple in association with Becker nevus vs. Becker nevus syndrome:
      a semantic problem only.

PMID- 9557900
TI  - Becker nevus syndrome and supernumerary nipples.

PMID- 9557901
TI  - Can we rely on the family history?

PMID- 9557902
TI  - Pilomatrixomas in Rubinstein-Taybi syndrome.

PMID- 9557904
TI  - Predictions of protein secondary structures using factor analysis on Fourier
      transform infrared spectra: effect of Fourier self-deconvolution of the amide I
      and amide II bands.
AB  - Fourier self-deconvolution (FSD) was performed on protein amide I and II Fourier
      transform infrared (FTIR) spectra to test if the resultant increased band shape
      variation would lead to improvements in protein secondary structure prediction
      with our factor analysis based restricted multiple regression (RMR) methods. FTIR
      spectra of 23 proteins dissolved in H2O were measured and normalized to a
      constant amide I peak absorbance. The deconvolved spectra were renormalized by
      area so that the deconvolved spectra sets had the same area as before. Principal
      component analysis of the deconvolved spectra sets was carried out, which was
      followed by a selective multiple linear regression (RMR) analysis of the
      principal component loadings with regard to the fractional components (FC) of
      secondary structure. As compared to analyses based on the original spectra set,
      helix and sheet predictions were not noticeably improved by FSD; but, if a very
      large number of component spectra (16) were retained in the pool to select which
      loadings to be used in the RMR optimization, better predictions of turn and
      "other" resulted. The prediction quality varied depending on the deconvolution
      parameters used.

PMID- 9557903
TI  - FTIR microspectroscopic study of cell types and potential confounding variables
      in screening for cervical malignancies.
AB  - FTIR microscopy was applied to the analysis of cell types and other variables
      present in Pap smears to ascertain the limitations of infrared spectroscopy in
      the diagnosis of cervical cancer and dysplasia. It was found that leukocytes, and
      in particular lymphocytes, have spectral features in the phosphodiester region
      (1300-900 cm[-1]) suggestive of what has previously been described as changes
      indicative of malignancy. Endocervical cells and fibroblasts have similar
      spectral features to HeLa cells and consequently could also confound diagnosis.
      The use of ethanol as a fixative and dehydrating agent results in retention of
      glycogen in cervical cell types and thus minimizes spectral changes in the
      glycogen region due to sampling technique. Spectra of seminal fluids exhibit
      strong bands in the phosphodiester/carbohydrate region; however, sperm
      contamination should be easily detectable by the presence of a distinctive
      doublet at 981/968 cm(-1). Erythrocyte spectra exhibit a reduction in glycogen
      band intensity, but can be discerned by a relatively low-intensity nu(s) PO2-
      band. Endocervical mucin spectra exhibit a reduction in glycogen bands and a very
      pronounced nu(s) PO2- band, which is similar in intensity to the corresponding
      band in HeLa cells. Thrombocytes have strong bands in the phosphodiester region,
      but thrombocytes can be discerned from other cell types by the presence of two
      small broad bands at 980 and 935 cm(-1). Candida albicans is characterized by
      strong bands in the polysaccharide region which could potentially obscure
      diagnostic bands if C. albicans is present in large numbers. Spectra of bacteria
      common to the female genital tract, in general, also have strong absorptions in
      the polysaccharide region; however, bacterial contamination is usually minimal
      and would not be expected to obscure cervical cell spectra. Nylon threads and
      bristles from cervical sampling implements produce characteristic IR profiles
      which allow for easy identification. Given the number of potential confounding
      variables associated with cervical cytology, a multivariate statistical or neural
      network analysis would appear to be necessary before the implementation of FTIR
      technology in clinical laboratories.

PMID- 9557905
TI  - Evidence for global mobility in the premelting of a polynucleotide from
      temperature-dependent Raman optical activity.
AB  - The backscattered Raman and Raman optical activity (ROA) spectra of poly(rA)
      poly(rU) at 20 degrees C and 45 degrees C in buffered aqueous solution between
      650 and 1750 cm(-1) are reported. Although the intensity of the majority of the
      Raman bands increase by varying amounts as the temperature is raised in
      accordance with the well-known hypochromic effect, the reverse effect is found
      for the ROA signals which we attribute to thermal accessibility of a greater
      number of distinct conformations leading to cancellation of ROA signals. The
      difference ROA spectrum obtained by subtracting the spectrum recorded at 45
      degrees C from that recorded at 20 degrees C displays a very similar sign pattern
      to those at both 20 degrees C and 45 degrees C throughout the spectral region
      examined. This indicates that the same average structure is maintained in this
      temperature range and that the thermal fluctuations are correlated through the
      bases, the glycosidic link, the sugar ring, and the phosphate backbone of both
      strands. These results indicate that ROA may be a useful new probe of the
      dynamics of nucleic acid in solution.

PMID- 9557906
TI  - FT-Raman investigation of alkaloids in the liana Ancistrocladus heyneanus.
AB  - The applicability of the micro-FT-Raman technique for studying alkaloids in vitro
      and for observing alkaloids in plant cells is demonstrated. This technique is
      examined using fresh plant material of Ancistrocladus heyneanus, a tropical liana
      known to produce pharmacologically interesting naphthylisoquinoline alkaloids as
      secondary metabolites. It will be shown that it is possible to localize and
      identify some of these alkaloids in different parts of the plant by means of
      Raman microspectroscopic studies. Data on the in situ structure and the spatial
      distribution can be obtained, which could provide information about the
      biosynthesis of the alkaloids in the plant.

PMID- 9557907
TI  - Luminescence and structure of the protonated forms of meso-tetraarylporphyrins in
      solution.
AB  - A comparative study of the spectral-luminescent properties (at 293 K and 77 K) of
      meso-tetrakis(o-tolyl)porphyrin (o-TTP) and meso-tetraphenylporphyrin (TPP), and
      also meso-tetrakis(n-propyl)porphyrin (TPrP) in nonaqueous acid media has been
      carried out with the aim to reveal effects associated with the influence of
      methyl groups which hinder sterically the twist of the phenyl rings enhancing
      their conjugation with the macrocycle in acid medium. On the basis of the
      spectral data it is concluded that although the introduction of the methyl groups
      diminishes this twist of phenyls it does not eliminate it completely (the
      absorption spectra of protonated o-TTP are intermediate between those of TTP and
      TPrP). The fluorescence spectra of the protonated forms of o-TTP and TPP at 77 K
      are approximately mirror-symmetrical to the Q(0-0) and Q(0-1) absorption bands;
      on the elevation of the temperature up to 293 K the fluorescence and absorption
      bands broaden, the Stokes shift largely increases, and the mirror symmetry of the
      spectra disappears, which is indicative of changes in solute-solvent interactions
      in the S1 state. The analysis of the obtained data on the energetics of
      photophysical processes leads to the conclusion that the significant role of
      radiationless deexcitation in the S1-->S0 channel, characteristic of the
      protonated form of TPP, is retained at 77 K. The introduction of the methyl
      groups at the ortho positions sharply decreases the corresponding rate constant,
      so that the S1-->T1 intersystem crossing becomes the main channel of
      deexcitation. The influence of heavy atoms (the Cl- and Br- anions) on the
      luminescence of the protonated forms has been investigated. It is shown that,
      analogous to the case of octaethylporphyrin investigated earlier, in nonaqueous
      media the protonated species of o-TTP form bis adducts of the dihydrochloride
      type. Contrary to this, the experiments with meso-tetrakis(p
      sulfophenyl)porphyrin (TPPS) in aqueous solutions have shown that the TPPS
      dications do not add counterions, whereas the influence of Cl- and Br- on
      fluorescence is realized according to the external heavy-atom effect mechanism.
      For nonaqueous o-TTP solutions with admixtures of HCl and CF3COOH the short
      wavelength fluorescence from the S3 (B1) level has been detected whose unusual
      peculiarity is its enhancement in passing from 293 K to 77 K.

PMID- 9557909
TI  - Death under anesthesia in the Middle East--a historical anecdote.

PMID- 9557908
TI  - Amphotericin B toxicity as related to the formation of oxidatively modified low
      density lipoproteins.
AB  - The effect of amphotericin B on the oxidation and degradation of low- and high
      density lipoproteins was investigated by UV-vis spectroscopy, electron
      microscopy, electrophoresis, and size-exclusion chromatography. Two formulations
      of the drug were used: the commercial Fungizone and a new, less toxic, liposomal
      formulation, AmBisome. It was shown that Fungizone strongly enhanced the
      oxidative deformation of low-density lipoprotein structure while AmBisome did not
      bind to this lipoprotein fraction and did not affect its oxidation. It was shown
      that amphotericin B contained in Fungizone extracted cholesterol from low-density
      lipoproteins which sensitized them to oxidation. Both formulations of
      amphotericin B studied here did not bind to high-density lipoprotein and did not
      affect the process of its oxidation.

PMID- 9557910
TI  - Prevention of post-operative nausea and vomiting following laparoscopic surgery-
      ephedrine vs propofol.
AB  - Postoperative nausea and vomiting (PONV) are relatively common troublesome
      distressing symptoms. The incidence is reported to be as high as 20-51%. Ninety
      adult ASA I and II patients scheduled for laparoscopic gynecological or surgical
      interventions, were randomly and equally assigned to one of the three groups in
      the immediate postoperative period: Group 1 received 0.1 ml.kg(-1) normal saline
      intravenously, while Group 2 received 0.5 mg.kg(-1) ephedrine intramuscularly and
      Group 3 received 0.25 mg.kg(-1) propofol intravenously as preventive antiemetic
      therapy. Sixty-six, 33 and 50 percent of patients experienced nausea and vomiting
      syndrome in Group 1, 2 and 3 respectively. Both ephedrine and propofol proved to
      have antiemetic properties. Ephedrine treated group of patient had significant
      less emetic score than propofol. No significant hemodynamic changes were recorded
      in both groups.

PMID- 9557911
TI  - Use of esmolol to attenuate hemodynamic responses during cataract extraction.
AB  - Esmolol attenuates hemodynamic responses to tracheal intubation and extubation in
      young patients, but has less well documented pharmacokinetics and efficacy in
      older patients. Following cataract surgery, application of pressure on the eye
      during eye bandaging may have vasomotor effects. The present study of older
      patients having cataract surgery investigated 1) the effects of normal saline 1.0
      ml. 10kg(-1) or esmolol 4.0 mg.kg(-1) IV given 90 secs prior to tracheal
      intubation and of normal saline 0.5 ml.10 kg(-1) or esmolol 2.0 mg.kg(-1) IV
      given 60 sec prior to each of eye bandaging and tracheal extubation; 2) the time
      to onset and duration of action of esmolol; 3) the cardiovascular effects of eye
      bandaging. Esmolol attenuated the cardiovascular effects of tracheal intubation,
      eye bandaging and tracheal extubation, but caused relative bradycardia and
      hypotension after induction and hypotension after extubation. Its effect occurred
      within 60-90 secs and lasted about 6 mins. Pressure on the eye during bandaging
      in those not given esmolol caused hypertension without tachycardia.

PMID- 9557912
TI  - Electroconvulsive therapy and intraocular pressure.
AB  - Psychiatric patients receiving phenothiazine, tricyclic antidepressant and
      antiparkinsonian drugs for prolonged periods, occasionally develop mydriasis and
      angle closure glaucoma. Suxamethonium, usually given to modify the convulsion of
      electroconvulsive therapy (ECT) increases intraocular pressure (IOP) by about 7-8
      mmHg, the increase being maximal and having returned to baseline 2 min and 6 mins
      after injection, respectively. We studied the effects on IOP of an electrically
      induced convulsion following induction of anesthesia using methohexitone 1 mg.kg(
      1) and suxamethonium 0.5 mg.kg(-1) in 21 consecutive cooperative psychiatric
      patients, all receiving antipsychotropic drugs. IOP was recorded sequentially
      from before induction of anesthesia to after resumption of spontaneous
      respiration. Their mean IOP was 15.3 (SD 3.7) mmHg prior to induction of
      anesthesia, 13.5 (SD 3.5) mmHg after loss of eyelash reflex following injection
      of methohexitone, 16.1 (SD 2.4) mmHg after cessation of muscle fasciculations
      induced by suxamethonium, 19.2 (SD 5.6) mmHg after cessation of convulsion and
      15.5 (SD 4.4) mmHg following resumption of regular spontaneous respiration. The
      successive stepwise changes in the mean IOP were all statistically significant (p
      < 0.001 each change compared with the preceding pressure; paired 't' tests).
      These data reveal that the reduction in IOP produced by methohexitone is reversed
      by the increase in IOP produced by suxamethonium. Collated with the time course
      of the effects of barbiturates and suxamethomium on IOP, the increase in IOP
      observed following the induced convulsion was not greater than that expected
      after suxamethonium alone, suggesting that the induced convulsion during ECT does
      not pose an ocular hazard to psychiatric patients receiving medications which
      have iatrogenic glaucomatous potential.

PMID- 9557913
TI  - Gastric emptying of indigestible solids--a rat model.
AB  - The effects of ingestion of digestion of digestible solids and liquids on gastric
      emptying of indigestible solids were studied. Thirty rats were allocated to one
      of five groups; in four groups, rats had been fasted for 24 h before the
      experiment, whereas in the fifth group, they had not been fasted. In all groups,
      ten steel balls (1.0 mm in diameter) were inserted through an orogastric cannula
      into the stomach under brief halothane anesthesia. In the four groups of fasted
      rats, one of the following substance was then given into the stomach: (1) 0.5 g
      digestible solids; (2) 1.0 ml saline; (3) 1.0 ml contrast medium (45% wv sodium
      diatrizoate); (4) no substance (control group). Three hours later, the number of
      balls which had passed into the intestine was counted. Ingestion of 0.5 g meal in
      fasted rats significantly delayed gastric emptying of steel balls (P < < 0.001),
      whereas there was no difference in gastric emptying of steel balls between fasted
      rats and fully fed rats. Ingestion of the contrast medium (P < < 0.001), but not
      that of saline, significantly delayed the emptying of the balls. Therefore,
      ingestion of digestible solids or liquids may delay gastric emptying of
      indigestible solids. Clinical implications of gastric emptying of indigestible
      solids are discussed.

PMID- 9557914
TI  - Post dural puncture headache--a review article.

PMID- 9557915
TI  - Use of the laryngeal mask for management of the compromised airway--a case
      report.
AB  - A 54-year old woman was scheduled for thoracotomy for excision of a tumor of the
      left upper lobe. Reduced thyromental distance and thyroid enlargement were
      identified by the preoperative physical examination and inability to visualize
      the larynx was encountered during direct laryngoscopy. A 37-Fr left sided double
      lumen tube was inserted in trachea with great difficulty after three failed
      attempts. One lung anesthesia underwent uneventfully and postoperatively it was
      decided to exchange the double lumen tube to a single lumen tracheal tube. After
      the extubation, five failed attempts of reintubation were performed. A laryngeal
      mask airway (LMA) size 3 was passed easily achieving an airtight airway. The
      patient underwent an uneventful prolonged (105 min) weaning via the LMA which was
      left in place until the patient regained full consciousness. Peripheral oxygen
      saturation remained greater than 95% throughout the airway manipulation. LMA
      insertion is an easy non-invasive technique and should be considered whenever
      airway management proves difficult.

PMID- 9557916
TI  - Dystonic movements following thalamonal and alfentanil induction--a case report.
AB  - A 62 year old woman developed dystonic movements following induction of
      anesthesia with thalamonal and alfentanil. The patient remained awake during the
      episode. A small dose of thiopental sodium followed by succinylcholine aborted
      the unpleasant state. The case is being presented to emphasize the point that
      even small doses of opioid narcotic can cause tonic movements and frank seizures
      in some patients.

PMID- 9557917
TI  - Will the millimetre of mercury be replaced by the kilopascal?

PMID- 9557918
TI  - Does it matter whether blood pressure measurements are taken with subjects
      sitting or supine?
AB  - BACKGROUND: Several guidelines for the management of hypertension do not give
      special preference to a specific position of the patient during blood pressure
      measurement, suggesting that blood pressure readings taken with patients sitting
      and with patients supine are interchangeable. OBJECTIVE: To test whether there is
      any difference between the blood pressure readings with patients sitting and
      supine. DESIGN AND METHODS: Blood pressure and heart rate were measured three
      times each for 245 subjects (171 hypertensives), with subjects both sitting and
      supine, simultaneously on both arms, with a Hawksley random-zero sphygmomanometer
      on the right arm and a semi-automatic oscillometric device (Bosomat) on the left
      arm. The sequence of the two positions was randomized. The procedure was repeated
      on a second occasion for 49 subjects (41 hypertensives) with the sequence of the
      positions reversed. Because there was no systematic difference among the three
      readings per position, the averages of the three blood pressure and heart rate
      readings with subjects sitting and supine were compared and the influences of
      age, body mass index, hypertension and medication on the difference were
      examined. RESULTS: We found no influence of the subject's body posture on the
      systolic blood pressure. We found a higher diastolic blood pressure [by 5.2+/-0.4
      mmHg (mean+/-SEM), P< 0.001 with Hawksley random-zero sphygmomanometer] and a
      greater heart rate [by 1.5+/-0.3 beats/min (mean+/-SEM), P< 0.001] with subjects
      sitting. The sitting minus supine differences for diastolic blood pressure and
      heart rate decreased significantly with increasing age (P< 0.001). We found no
      effect of body mass index, hypertension and medication on the sitting - supine
      differences. CONCLUSIONS: The subject's body posture influenced especially the
      diastolic blood pressure and heart rate, both of them being significantly higher
      with patients sitting rather than supine. This effect decreased with age. Thus,
      for indirect blood pressure measurement, diastolic blood pressure values obtained
      with subjects sitting and supine cannot automatically be regarded as equivalent.

PMID- 9557919
TI  - Family history as a predictor of blood pressure in a longitudinal study of
      Australian children.
AB  - BACKGROUND: Sex both of parent and of child might influence associations between
      parental hypertension and blood pressure in offspring. OBJECTIVE: To examine
      these associations. DESIGN: A cohort of Australians was surveyed 3-yearly from
      age 9 to 18 years. SETTING: A community-based sample. PARTICIPANTS: When they
      were aged 18 years, 630 of 1565 participants who had been selected randomly at
      the age of 9 years were re-surveyed. MAIN OUTCOME MEASURES: Systolic and
      diastolic blood pressures. RESULTS: Paternal hypertension was reported by 18% of
      men and 15% of women and maternal hypertension by 15% of men and 14% of women. By
      the time they were aged 9 years, systolic blood pressure was significantly higher
      in sons [117.8 mmHg, 95% confidence interval (CI) 116A-119.2 versus 114.7 mmHg,
      CI 113.4-116.0] and daughters (118.2 mmHg, CI 116.9-119.5 versus 114.9 mmHg, CI
      112.8-117.0) of hypertensive fathers than it was in sons and daughters of
      normotensive fathers. When they were aged 18 years, paternal hypertension
      predicted blood pressures in men and women independently of their weight at
      birth, fitness, alcohol consumption and weight for height for age. Systolic blood
      pressures increased more rapidly (by 0.6 mmHg/year) in men with hypertensive
      fathers. CONCLUSIONS: Systolic blood pressure in young adults differs in relation
      to parental hypertension according to the sex of the affected parent and the sex
      of the offspring. This could reflect unmeasured environmental variables or the
      action of sex-related genetic or intrauterine factors.

PMID- 9557920
TI  - Trends in the prevalence, detection, treatment and control of arterial
      hypertension in the Belgian adult population.
AB  - OBJECTIVES: To discuss changes during the past decades in the prevalence and in
      the patterns of detection, treatment and control of arterial hypertension in the
      general Belgian population aged 25-64 years. DESIGN: Data from two cross
      sectional cardiovascular disease risk factor surveys of the general population
      aged 25-64 years during the first and second halves of the 1980s (the Belgian
      Inter-university Research on Nutrition and Health study of 1980-1984 and the
      World Health Organization Multinational Monitoring of Trends and Determinants in
      Cardiovascular Diseases study of 1985-1992) are compared. PARTICIPANTS: Age
      stratified and sex-stratified random samples from the general population yielded
      9372 participants in the former study and 4904 participants in the latter.
      METHODS: In both studies, blood pressure measurements and other variables were
      collected in the same standardized way and by the same observers. RESULTS: For
      both sexes, overall age-standardized prevalences of hypertension (subjects with
      systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95
      mmHg or currently being administered antihypertensive drug treatment) were found
      to be significantly (P< 0.001) higher in the former than they were in the latter
      study. A significant decline in population mean systolic blood pressure values
      was observed for both sexes on going from the former data to the latter (falls of
      6.0 and 7.3 mmHg for men and women, respectively, P< 0.01). In log-linear models,
      adjusted for age, a highly significant (P< 0.0001) favourable shift in the
      population distribution over the various categories of detection, treatment and
      control of hypertension was observed. This trend exhibited a significant sex
      difference, however, there being a much more favourable trend for women.
      CONCLUSIONS: In Belgium, favourable trends in the prevalence and in the patterns
      of detection, treatment and control of arterial hypertension and in the levels of
      systolic blood pressure were observed. The so-called 'rule of halves' is no
      longer valid.

PMID- 9557921
TI  - Endocrinological abnormalities in angiotensinogen-gene knockout mice: studies of
      hormonal responses to dietary salt loading.
AB  - OBJECTIVE: Physiological roles of the renin-angiotensin system in maintaining
      blood pressure and sodium-water balance in angiotensinogen gene-knockout mice
      were evaluated with special reference to endogenous pressor substances. METHODS:
      Angiotensinogen-gene knockout mice and control mice were fed a 0.3 or 4% NaCl
      diet for 2 weeks. Systolic blood pressure and urinary excretions of electrolytes,
      creatinine, aldosterone, adrenaline, noradrenaline, dopamine and vasopressin were
      measured. RESULTS: About 60% of our angiotensinogen-gene knockout mice did not
      survive until weaning. These mice presented with hypotension and polyuria.
      Urinary excretion of aldosterone from such mice was significantly lower (not
      detected) than that from control mice (2.0+/-0.3 pg/mg creatinine). In contrast,
      urinary excretion of vasopressin from angiotensinogen-gene knockout mice (0.7+/
      0.1 ng/mg creatinine) was greater than that from control mice (0.3+/-0.1 ng/mg
      creatinine), and those of adrenaline and of noradrenaline were similar for
      knockout and control mice. After salt loading (a 4% NaCl diet), angiotensinogen
      gene knockout mice exhibited a significant increase in systolic blood pressure
      (from 68.3+/-2.9 to 95.9+/-5.9 mmHg), significant decreases in urinary excretions
      of adrenaline (from 65+/-8 to 40+/-7 pg/mg creatinine) and noradrenaline (from
      467+/-48 to 281+/-41 pg/mg creatinine) and no change in excretion of vasopressin
      compared with such mice fed a 0.3% NaCl diet CONCLUSION: The present results with
      angiotensinogen-gene knockout mice confirm that the renin-angiotensin system
      plays fundamental roles in maintaining the blood pressure and sodium-water
      balance. Because the vasopressin and catecholaminergic systems may be altered by
      lack of angiotensin in angiotensinogen-gene knockout mice, these systems perhaps
      are not able to restore blood pressure and sodium-water depletion to normal
      levels in these mice.

PMID- 9557922
TI  - Plasma hydrogen peroxide production in hypertensives and normotensive subjects at
      genetic risk of hypertension.
AB  - BACKGROUND: Oxygen free radicals may play roles in hypertension both in
      arteriolar constriction and in formation of lesions. OBJECTIVE: To quantify free
      radical production in blood plasma of genetic hypertensives. DESIGN: Hydrogen
      peroxide levels were measured, because it is one of the most stable reactive
      oxygen species. METHODS: An electrode technique was used to determine plasma
      hydrogen peroxide levels after blockade of endogenous catalase with sodium azide.
      This method was validated by an independent spectrophotometric technique.
      RESULTS: Members of the essential hypertensive group (n=21) had higher plasma
      hydrogen peroxide levels (3.16+/-0.14 versus 2.50+/-0.16 micromol/l, P=0.005)
      than did members of the normotensive group (n=29). Furthermore, within the
      normotensive group, those with a family history of hypertension (n=15) exhibited
      higher hydrogen peroxide levels (2.83+/-0.27 versus 2.14< or =0.13 micromol/l,
      P=0.03) than did those without such a family history (n=14). Plasma hydrogen
      peroxide levels in these 50 subjects were correlated to their mean arterial
      pressures (r=0.54, P < 0.001). When hypertensives were grouped with normotensives
      without a family history of hypertension, the correlation improved (r=0.70, P<
      0.001). Statistical analysis (two-way analysis of variance) revealed that a
      family history of hypertension was a better predictor of plasma hydrogen peroxide
      production than was blood pressure status (P=0.003 versus P=0.093). Further
      investigations showed that superoxide is produced in plasma and that one of its
      sources is xanthine oxidase. CONCLUSIONS: Hydrogen peroxide is produced in blood
      plasma and elevation of its level could constitute a pathogenic factor in
      vascular organ damage attendant upon systemic hypertension.

PMID- 9557923
TI  - Activation by calcium of erythrocyte Na+/H+ exchange in men.
AB  - OBJECTIVE: To determine whether protein kinase C is necessary for the calcium
      activation of the Na+/H+ exchange in human erythrocytes by studying activation by
      calcium of erythrocyte Na+/H+ exchange in control cells, in protein kinase C
      depleted cells after downregulation of protein kinase C with phorbol-12-myristate
      13-acetate and in cells that had been treated beforehand with phorbol-12
      myristate-13-acetate with and without the calpain inhibitor E-64d. METHODS:
      Erythrocyte Na+/H+ exchange was measured by determining the initial rates of the
      influx of Na+ into Na+-depleted, acid loaded cells. The effects of various
      concentrations (0-1 mmol/l) of CaCl2 and the effects of 1 mmol/l CaCl2 on
      activation of the intracellular pH and on the external Na+ activation of Na+/H+
      exchange were studied. The effects of 1 mmol/l CaCl2 on Na+/H+ exchange in
      control cells and cells that had been incubated beforehand with and without 1
      micromol/l phorbol-12-myristate-13-acetate and with E-64d and 1 micromol/l
      phorbol-12-myristate-13-acetate for 1, 2, 3 and 24 h were also investigated.
      RESULTS: Addition of Ca2+ to a concentration in the range 0-1 mmol/l in the
      presence of calcimycin resulted in stimulation of Na+/H+ exchange: 1 mmol/l CaCl2
      increased (P< 0.001) the erythrocyte Na+/H+ exchange by 74%. Calcium increased
      the maximum rate for activations by intracellular pH and by external Na+ of
      Na+/H+ exchange, whereas it did not affect the Michaelis-Menten constants for
      activation by intracellular H+ and external Na+. However, calcium did not
      activate the Na+/H+ exchange in protein kinase C downregulated erythrocytes and
      administration of the calpain inhibitor E-64d could not prevent this
      inactivation. CONCLUSION: Our data indicate that protein kinase C is necessary
      for the activation by calcium of the erythrocyte Na+/H+ exchange.

PMID- 9557924
TI  - Potent 'new pressor protein' related to coagulation factor XII is potentiated by
      inhibition of angiotensin converting enzyme.
AB  - BACKGROUND: 'New pressor protein' was observed after tryptic activation of human
      and rat plasma in vitro, which is done conventionally for prorenin measurements.
      RESULTS: It is potently pressor, heat labile, possesses enzyme activity, and has
      a relative molecular mass > 30 kDa with isoelectric point(s) 4.7-4.9. New pressor
      protein equivalent to only 0.01 ml human, or rat, plasma injected intravenously
      quickly raises systolic blood pressure in 300 g anesthetized, ganglion-blocked,
      bioassay rats by about 15 mmHg. For unknown reasons, this is potentiated to about
      45 mmHg after treatment with angiotensin I converting enzyme inhibitors (such as
      captopril and enalapril). New pressor protein activity in rats remains normal 24
      h after bilateral nephrectomy, suggesting that it has an extrarenal origin and,
      furthermore, excluding the possibility of an association with renin-angiotensin
      system. Systolic blood pressure elevation is greater than the diastolic one,
      implicating cardiotonic effects. Human plasma new pressor protein was purified
      using standard biochemical techniques and its N-terminal sequence (19 residues)
      found to be homologous with the beta factor XIIa fragment of coagulation factor
      XII. This was supported by demonstrating inhibition of new pressor protein
      activity in vitro using the factor XII-specific corn trypsin inhibitor. Also,
      human new pressor protein activity in humans congenitally deficient in
      coagulation factor XII is very low. The high potency and multiphasic, cardiotonic
      effects of injected new pressor protein suggest that it interacts synergistically
      with other systems in the body. This was confirmed by showing that, within 10 min
      of total bilateral adrenalectomy, responses to new pressor protein decreased
      markedly. CONCLUSIONS: New pressor protein's action requires adrenal (medullary?)
      involvement, but its mechanism of action and that of its potentiation by
      angiotensin converting enzyme inhibitors remain unknown. The physiologic and
      clinical relevance of these observations depends on whether activation of new
      pressor protein can occur in vivo.

PMID- 9557925
TI  - Low-dose transdermal scopolamine decreases blood pressure in mild essential
      hypertension.
AB  - BACKGROUND: Increasing cardiovascular parasympathetic nervous activity could have
      antihypertensive effects. Low-dose transdermal scopolamine increases vagal
      cardiac modulation of sinus node and baroreflex sensitivity in healthy subjects
      and in cardiac patients. OBJECTIVE: To study the short-term effects of
      transdermal scopolamine on blood pressure and cardiovascular autonomic control in
      patients with mild essential hypertension. DESIGN: A randomized, double-blind,
      placebo-controlled crossover trial with 12 untreated middle-aged [aged 39+/-5
      years (mean+/-SD)] patients with mild essential hypertension. METHODS: We
      recorded the electrocardiogram, auscultatory sphygmomanometric and continuous
      photoplethysmographic finger arterial pressure, and spirometry signals with
      patients supine and 70 degrees tilted during controlled (0.25 Hz) breathing.
      Cardiovascular autonomic regulation was analyzed with power spectrum analysis of
      R-R interval and arterial pressure variability and a spontaneous sequence method
      for baroreflex sensitivity. In addition, a deep-breathing test was performed to
      assess maximal breathing-related sinus arrhythmia. RESULTS: Transdermal
      scopolamine treatment significantly decreased blood pressure both when patients
      lay supine and when they were in the 70 degrees tilted position. Scopolamine also
      slowed heart rate and increased baroreflex sensitivity and R-R interval high
      frequency variability for both body positionings. In addition, scopolamine
      accentuated respiratory sinus arrhythmia during deep breathing and blunted the
      tilt-induced increase in heart rate. Scopolamine did not affect blood pressure
      variability. CONCLUSIONS: Transdermal scopolamine decreases arterial pressure,
      increases baroreflex sensitivity and accentuates vagal-cardiac modulation of
      sinus node in patients with mild hypertension. Our study supports the hypothesis
      that increasing cardiovascular parasympathetic activity could have
      antihypertensive effects in essential hypertension.

PMID- 9557927
TI  - Enhanced inhibition by melatonin of alpha-adrenoceptor-induced aortic contraction
      and inositol phosphate production in vascular smooth muscle cells from
      spontaneously hypertensive rats.
AB  - OBJECTIVE: To test the hypothesis that the enhanced inhibition by melatonin of
      the norepinephrine-induced vasoconstriction and formation of inositol phosphate
      in spontaneously hypertensive rats are mediated by its antioxidant effect
      METHODS: Aortic rings from spontaneously hypertensive rats and age-matched Wistar
      Kyoto rats were used for measuring vascular contraction forces. Cultured aortic
      smooth muscle cells were prelabelled with myo-[2-3H]-inositol for evaluation of
      formation of inositol phosphate after exposure to agonist or antagonist Basal or
      forskolin-induced formation of cyclic AMP was evaluated using a [3H]-cyclic AMP
      assay system. Oxygen-derived free radicals were generated with a hypoxanthine and
      xanthine oxidase system. RESULTS: The inhibition of the norepinephrine-induced
      aortic contraction by melatonin was more potent in spontaneously hypertensive
      than it was in Wistar-Kyoto rats. The inhibition of the norepinephrine-induced
      formation of inositol phosphate by 0.3-300 micromol/l melatonin was also greater
      in smooth muscle cells from spontaneously hypertensive rats than it was in those
      cells from Wistar-Kyoto rats. In contrast, the inhibition of the norepinephrine
      induced formation of inositol phosphate in smooth muscle cells from spontaneously
      hypertensive and Wistar-Kyoto rats by 2-iodomelatonin, an agonist of melatonin
      receptors, was not different. Prazosin, but not yohimbine, eliminated or
      partially inhibited the norepinephrine-induced formation of inositol phosphate in
      smooth muscle cells from Wistar-Kyoto rats or from spontaneously hypertensive
      rats, respectively. In the presence both of prazosin and of melatonin, the
      norepinephrine-induced production of inositol phosphate was abolished in smooth
      muscle cells from spontaneously hypertensive rats. Furthermore, superoxide
      dismutase significantly inhibited the norepinephrine-induced aortic contraction
      and formation of inositol phosphate in smooth muscle cells from spontaneously
      hypertensive rats, but not in those cells from Wistar-Kyoto rats. In contrast,
      catalase had no effect on the norepinephrine-induced formation of inositol
      phosphate and vascular contraction either in cells from spontaneously
      hypertensive rats or in cells from Wistar-Kyoto rats. Hypoxanthine-xanthine
      oxidase induced formation of more inositol phosphate in smooth muscle cells from
      spontaneously hypertensive rats than it did in those from Wistar-Kyoto rats.
      Melatonin and superoxide dismutase similarly inhibited the hypoxanthine-xanthine
      oxidase-induced formation of inositol phosphate more in cells from spontaneously
      hypertensive rats than it did in those from Wistar-Kyoto rats. However, melatonin
      had no effect either on basal or on the forskolin-induced formation of cyclic AMP
      in smooth muscle cells from rats of both strains. CONCLUSION: The enhanced
      inhibitory effect of melatonin on the norepinephrine-induced cellular production
      of inositol phosphate in spontaneously hypertensive rats was not mediated by
      melatonin receptors or alpha-adrenoceptors. Rather, the antioxidant effect of
      melatonin could become important in spontaneously hypertensive rats, which are
      suspected to have a lower cellular content of antioxidants or a greater
      sensitivity to superoxide anions, or both, of the vascular tissue.

PMID- 9557926
TI  - Forearm vasorelaxation in hypertensive renal transplant patients: the impact of
      withdrawal of cyclosporine.
AB  - OBJECTIVE: To determine whether cyclosporine A-induced hypertension in renal
      transplant recipients is accompanied by impairment of endothelium-dependent
      vasodilatation, which has been suggested by in-vitro and in-vivo animal
      experiments. DESIGN AND METHODS: In-vivo endothelium-dependent and endothelium
      independent vasodilatation, and plasma concentrations of vasoactive hormones in
      16 renal transplant patients were determined while they were being treated with
      cyclosporine A, and 16 weeks later, after their treatment had been changed to
      azathioprine therapy. The vasodilator response of the forearm vascular bed was
      measured by strain gauge venous occlusion plethysmography during intra-arterial
      infusion of acetylcholine (endothelium-dependent vasodilatation) and
      nitroprusside (endothelium-independent vasodilatation). Postischemic reactive
      flow was measured after 10 min of arterial occlusion. In addition, plasma
      concentrations of norepinephrine, and the prostanoids prostaglandin E2 and
      thromboxane B2, and also concentration of cyclosporine A in blood, were measured.
      Glomerular filtration rate and renal blood flow were estimated 1 day before the
      plethysmography study during each treatment period. RESULTS: Upon changing from
      cyclosporine A to azathioprine treatment, mean arterial pressure fell
      significantly by 12+/-3% (P< 0.05). Glomerular filtration rate and renal blood
      flow increased by 13+/-5 and 19+/-8%, respectively (both P< 0.05), while renal
      vascular resistance fell by 48+/-11% (P< 0.01). Both baseline forearm blood flow
      and baseline forearm resistance did not change after conversion (5.7+/-0.7 versus
      4.9+/-0.6 ml/100 ml/min, and 27.3+/-4.2 versus 26.2+/-3.2 arbitrary units). The
      absolute and relative forearm blood flow responses, and forearm vascular
      resistance responses to infusions of acetylcholine and nitroprusside were similar
      during treatments with cyclosporine A and azathioprine. Peak postischaemic
      forearm blood flow was 42+/-12% higher during cyclosporine A treatment than it
      was during azathioprine treatment (P< 0.05), but the minimal postischaemic
      forearm vascular resistance did not differ for these treatments. Plasma
      prostaglandin E2 and thromboxane B2 levels decreased by 34+/-7 and 45+/-8%,
      respectively, after changing treatment, but norepinephrine levels did not change.
      CONCLUSIONS: Our data indicate that cyclosporine A-induced hypertension in renal
      transplant recipients is not accompanied by an increase in forearm vascular
      resistance. In addition, changing from cyclosporine A to azathioprine treatment
      did not cause changes in endothelial vasodilator functioning, although mean
      arterial pressure decreased significantly. Our results do not support the
      hypothesis that attenuation of endothelial vasodilator functioning contributes to
      the development of cyclosporine A-induced hypertension.

PMID- 9557928
TI  - Different effects of calcium antagonists on fluid filtration of large arteries
      and albumin permeability in spontaneously hypertensive rats.
AB  - OBJECTIVE: To compare the effects of chronic administration of two
      dihydropyridines, nifedipine and amlodipine, and the non-dihydropyridine Ca2+
      antagonist mibefradil on fluid filtration of large arteries and extravasation of
      albumin in spontaneously hypertensive rats. METHODS: Spontaneously hypertensive
      rats aged 2 months were randomly allocated to oral treatment once a day with 30
      mg/kg mibefradil (n=12), 100 mg/kg nifedipine (n=12), 20 mg/kg amlodipine (n=12)
      or placebo (n=12) for 1 month. Instantaneous blood pressure of rats under
      pentobarbital anaesthesia was recorded at the end of the treatment Fluid
      filtration across the carotid arterial wall was determined in situ in the
      isolated carotid artery. Extravasation of 25 mg/kg Evans Blue dye that had been
      injected intravenously was used to assess whole vascular permeability to albumin
      after chronic treatment with mibefradil. RESULTS: Similar reductions in mean
      arterial pressure were obtained in all Ca2+ antagonist-treated rats. Heart rate
      was similar in rats in control, nifedipine and amlodipine groups but was
      significantly lower in mibefradil-treated rats (by 19%, P< 0.001). Fluid
      filtration across the carotid wall was greater in all Ca2+ antagonist-treated
      animals. However, fluid filtration was significantly less in mibefradil-treated
      rats than it was in nifedipine-treated, and amlodipine-treated rats. Furthermore,
      administration of mibefradil did not significantly modify extravasation of
      albumin in all tested tissues (pancreas, testis, spleen, lung, kidney, intestine,
      liver, skeletal muscle) except for cardiac and brain tissues, in which the
      permeability of albumin was increased by 24 and 33%, respectively, compared with
      values for the control group (P < 0.05). CONCLUSION: These results indicate that
      Ca2+ antagonists increase fluid filtration through large arteries from
      spontaneously hypertensive rats. That the lower fluid filtration in mibefradil
      treated rats was associated with no change in extravasation of albumin in most
      tissues and especially in skeletal muscle suggests that vascular permeability in
      hypertensive rats was impaired less by mibefradil treatment than it was by
      dihydropyridine Ca2+ antagonist treatments.

PMID- 9557929
TI  - A study of the interactive effects of oral contraceptive use and dietary fat
      intake on blood pressure, cardiovascular reactivity and glucose tolerance in
      normotensive women.
AB  - OBJECTIVE: To investigate the interactive effects of oral contraceptive pill use
      and dietary fat intake on cardiovascular haemodynamics and metabolic parameters
      in young normotensive women. DESIGN: Thirty-two women participated, of whom 16
      were taking oral contraceptive pills (ethinyl-oestradiol plus levonorgestrel) and
      16 were age-matched and weight-matched controls not taking such pills. Subjects
      consumed either a high-fat or a low-fat diet for 2 weeks in an open, randomized,
      crossover study lasting 6 weeks. Investigations were performed at the end of each
      diet during the luteal phase of the menstrual cycle. METHODS: Blood pressure was
      measured by 24 h ambulatory recording; cardiovascular reactivity was determined
      by examining blood pressure responses to systemic infusions of noradrenaline and
      angiotensin II and to the cold pressor test; and carbohydrate metabolism was
      investigated by an intravenous glucose-tolerance test. RESULTS: Plasma
      triglyceride levels were significantly higher in women taking oral contraceptive
      pills compared with non-users on both diets; however, responses of lipoprotein
      levels to the two diets did not differ between study groups (total and low
      density lipoprotein cholesterol levels decreased by 15 and 17% in oral
      contraceptive pill users and by 14% each in non-users, on the low-fat compared
      with the high-fat diet). Fasting plasma insulin levels, the insulin-production
      response to administration of glucose (insulin area under the curve) and resting
      clinic and night-time systolic blood pressures were all significantly reduced on
      the low-fat diet, but only in non-users. Blood pressure responses to
      noradrenaline and maximal heart rate response to cold were significantly
      attenuated during the low-fat diet in oral contraceptive pill users. During the
      low-fat diet, resting systolic, 24 h systolic and diastolic blood pressures and
      insulin area under the curve were all significantly higher for women taking the
      oral contraceptive pills. Users of these pills also exhibited a greater systolic
      sensitivity to administration both of noradrenaline and of angiotensin II and had
      a higher plasma renin activity irrespective of dietary phase. CONCLUSIONS: These
      results confirm that oral contraceptive pills have the potential to cause adverse
      effects on blood pressure, cardiovascular reactivity and the insulin-production
      response to administration of glucose and suggest that some of the beneficial
      effects of a low-fat diet on these parameters may be negated in women taking oral
      contraceptive pills.

PMID- 9557930
TI  - The impact of genetic hypertension on insulin secretion and glucoregulatory
      control in vivo: studies with the TGR(mRen2)27 transgenic rat.
AB  - OBJECTIVE: To examine the associations among hypertension, insulin secretion,
      glucose tolerance and insulin resistance in vivo. DESIGN: Glucose tolerance and
      insulin secretion during an intravenous glucose tolerance test and action of
      insulin on whole-body glucose kinetics in the post-absorptive state and during
      hyperinsulinaemia were examined in conscious, unrestrained TGR(mRen2)27 rats and
      age-matched transgene-negative controls. METHODS: Glucose tolerance and insulin
      secretion were examined after intravenous administration of 500 mg glucose/kg
      body weight. Endogenous glucose production and whole-body glucose disposal were
      estimated using [3-3H]-glucose during euglycaemic-hyperinsulinaemic clamping.
      Muscle glucose utilization was estimated using 2-deoxy-[1-3H]-glucose. RESULTS:
      Despite there being higher insulin levels, whole-body glucose turnover was
      significantly lower in post-absorptive TGR(mRen2)27 rats than it was in transgene
      negative controls. This was associated with significant suppression of glucose
      uptake/phosphorylation by oxidative skeletal muscles. TGR(mRen2)27 rats also
      exhibited significantly lower blood glucose levels, higher plasma insulin levels
      and higher rates of disappearance of glucose after intravenous administration of
      glucose. During hyperinsulinaemia, steady-state glucose infusion rates required
      to maintain euglycaemia in TGR(mRen2)27 rats were significantly greater,
      indicating that an increase in whole-body action of insulin had occurred. This
      was due to significantly greater suppression of endogenous production of glucose:
      insulin-stimulated glucose disposal rates did not differ significantly between
      the two groups. CONCLUSIONS: The results indicate that TGR(mRen2)27 rats have an
      enhanced and sensitized insulin-secretory response to glucose, together with a
      greater than normal hepatic action of insulin. Insulin-mediated glucose disposal
      was not impaired. The results therefore do not support the hypothesis that
      hypertension plays a primary role in the development of insulin resistance.

PMID- 9557931
TI  - Angiotensin converting enzyme inhibition modulates cardiac fibroblast growth.
AB  - BACKGROUND: The progression of left ventricular hypertrophy and cardiac fibrosis
      in hypertensive heart disease is influenced by sex and age. Although angiotensin
      converting enzyme inhibition has been shown to prevent progression of the disease
      in postmenopausal women, the interaction of angiotensin II and estrogen in this
      process before and after the menopause is poorly understood. OBJECTIVE: To
      investigate the influence of the angiotensin converting enzyme inhibitor
      moexiprilat on serum, estrogen and angiotensin II-induced cardiac fibroblast
      growth. METHODS: Neonatal rat cardiac fibroblasts were incubated with 1 and 10%
      fetal calf serum, 10(-7) mol/l angiotensin II, 10(-9) mol/l estrone, 10(-9) mol/l
      17beta-estradiol and 10(-8) mol/l moexiprilat. Proliferation was measured in
      terms of incorporation of bromodeoxyuridine. Western blot analysis was performed
      using antibodies directed against the growth-related immediate early genes c-fos
      and Sp-1. All experiments were performed at least three times. RESULTS: Fetal
      calf serum stimulated cardiac fibroblast proliferation (1% fetal calf serum 2.0+/
      0.028-fold; 10% fetal calf serum 2.7+/-0.028-fold). Angiotensin II and estrone
      stimulated proliferation of cardiac fibroblasts grown in the absence of fetal
      calf serum (angiotensin II 4.2+/-0.075-fold; estrone 2.9+/-0.034-fold) and
      further increased proliferation in the presence of 1% fetal calf serum
      (angiotensin 11 4.3+/-0.072-fold); estrone 3.8+/-0.045-fold) and 10% fetal calf
      serum (angiotensin II 4.8+/-0.112-fold; estrone 4.1+/-0.047-fold). Coincubation
      with moexiprilat specifically inhibited proliferation induced by angiotensin II
      and estrone but not by serum, and angiotensin II type 1 receptor blockade
      inhibited angiotensin II-induced but not estrone-induced cell growth. Western
      blot analysis showed that the expression of c-fos and Sp-1 was induced in a time
      dependent fashion by angiotensin II (to maxima of 5.0-fold for c-fos and 3.0-fold
      for Sp-1) and estrone (15.2-fold for c-fos and 6.2-fold for Sp-1). This effect
      was completely inhibited by moexiprilat. CONCLUSIONS: Angiotensin converting
      enzyme inhibition modulates cardiac fibroblast growth induced by angiotensin II
      and estrone. This mechanism might contribute to the beneficial effects of
      angiotensin converting enzyme inhibition in postmenopausal patients with
      hypertensive heart disease.

PMID- 9557932
TI  - Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan
      versus enalapril in hypertensive patients.
AB  - OBJECTIVE: To compare the acute and sustained renal hemodynamic effects on
      hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily.
      PATIENTS: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate
      essential hypertension and normal serum creatinine levels completed this study.
      STUDY DESIGN: After random allocation to treatment (n=10 per group),
      administration schedule (morning or evening) was determined by further random
      allocation, with crossover of schedules after 6 weeks' therapy. Treatment and
      administration assignments were double-blind. Twenty-four-hour ambulatory blood
      pressure was monitored before and after 6 and 12 weeks of therapy. Renal
      hemodynamics were determined on the first day of drug administration and 12 and
      24 h after the last dose during chronic treatment. RESULTS: Administration of
      each antihypertensive agent induced a renal vasodilatation with no significant
      change in glomerular filtration rate. However, the time course appeared to
      differ: irbesartan had no significant acute effect 4 h after the first dose, but
      during chronic administration a renal vasodilatory response was found 12 and 24 h
      after the dose; enalapril was effective acutely and 12 h after administration,
      but no residual effect was found 24 h after the dose. Both antihypertensive
      agents lowered mean ambulatory blood pressure effectively, with no significant
      difference between treatments or between administration schedules (morning versus
      evening). CONCLUSIONS: Irbesartan and enalapril have comparable effects on blood
      pressure and renal hemodynamics in hypertensive patients with normal renal
      functioning. However, the time profiles of the renal effects appear to differ,
      which might be important for long-term renoprotective effects.

PMID- 9557934
TI  - Is hyperinsulinaemia during withdrawal of ethanol due to an increase in secretion
      of insulin or a decrease in clearance of insulin?

PMID- 9557933
TI  - Assessment of control of hypertension in the population.

PMID- 9557935
TI  - Stage-related chondrogenic potential of human limb bud mesenchyme cells, in
      vitro: role of protein kinase C.

PMID- 9557936
TI  - Extracellular matrix interferes with colorimetric estimation of cell number.

PMID- 9557937
TI  - Fibronectin production by cultured human lung fibroblasts in three-dimensional
      collagen gel culture.
AB  - In vivo, fibroblasts are distributed in a three-dimensional (3-D) connective
      tissue matrix. Fibronectin is a major product of fibroblasts in routine cell
      culture and is thought to regulate many aspects of fibroblast biology. In this
      context, we sought to determine if the interaction of fibroblasts with a 3-D
      matrix might affect fibronectin production. To examine this hypothesis,
      fibronectin production by fibroblasts cultured in a 3-D collagen gel or on
      plastic dishes was measured by ELISA. Fibroblasts in 3-D gel culture produced
      more fibronectin than those in monolayer culture. Fibroblasts in 3-D culture
      produced increasing amounts of fibronectin when the collagen concentration of the
      gel was increased. The 3-D nature of the matrix appeared to be crucial because
      plating the fibroblasts on the surface of a plastic dish underneath a collagen
      gel was not different from plating them on a plastic dish in the absence of
      collagen. In addition to increased fibronectin production, the distribution of
      the fibronectin produced in 3-D culture was different from that of monolayer
      culture. In monolayer culture, more than half of the fibronectin was released
      into the culture medium. In 3-D culture, however, approximately two-thirds
      remained in the collagen gel. In summary, the presence of a 3-D collagen matrix
      increases fibroblast fibronectin production and results in greater retention of
      fibronectin in the vicinity of the producing cells.

PMID- 9557938
TI  - Culture of human main pancreatic duct epithelial cells.
AB  - Attempts to grow human pancreatic duct epithelial cells in long-term culture have
      proven difficult. We have developed a system of growing these cells for several
      passages by adapting methods used to culture dog pancreatic duct cells.
      Epithelial cells were enzymatically dissociated from the main pancreatic duct and
      plated onto collagen-coated culture inserts suspended above a human fibroblast
      feeder layer. After primary culture, the cells were either passaged onto new
      inserts or plastic tissue culture plates in the absence of collagen. Cells grown
      on the latter plates were maintained in a serum-free medium. Primary pancreatic
      duct epithelial cells grow steadily to confluence as a monolayer in the feeder
      layer system. After primary culture, cells passaged onto new inserts with fresh
      feeder layer or plastic plates and fed with serum-free medium continued to
      develop into confluent monolayers for up to four passages. The cells were
      columnar with prominent apical microvilli, sub-apical secretory vesicles, and
      lateral intercellular junctions resembling the morphology of normal in vivo
      epithelial cells. These cells were also positive for cytokeratin 19, 7, and 8 and
      carbonic anhydrase II, as measured by immunohistochemistry. Metabolically, these
      cells synthesized and secreted mucin, as measured by incorporation of tritiated N
      acetyl-D-glucosamine. In conclusion, we demonstrated that human pancreatic
      epithelial cells from the main duct can be successfully grown in culture and
      repeatedly passaged using a feeder layer system, with serum-free medium, and in
      organotypic cultures.

PMID- 9557940
TI  - Properties of a polarized primary culture from rat renal inner medullary
      collecting duct (IMCD) cells.
AB  - A primary culture from rat renal IMCD cells was established to investigate the
      permeability characteristics of the luminal and contraluminal plasma membranes of
      the papillary collecting duct in vitro. Freshly isolated IMCD cells were grown on
      filters in a special "epithelial cell" medium. Confluency was proved with an
      epithelial volt/ohm meter. After 7 d of culture the transepithelial resistance
      reached more than 1000 omega x cm2. A polarization of the cells with regard to a
      basolateral localization of a lactate efflux system, and an L-alanine transport
      system was achieved. The hypotonicity-activated release systems for the organic
      osmolytes sorbitol and betaine were also located basolaterally, whereas taurine,
      glycerophosphorylcholine, and myo-inositol left the cells at both cell poles but
      with different capacity. Morphological observations revealed also that the
      monolayer was well differentiated. Thus, a model of a renal collecting duct
      epithelium was established which can be used to analyze polarized and
      differentiated transport processes across the epithelial cells and their plasma
      membranes.

PMID- 9557939
TI  - A comparative molecular analysis of four rat smooth muscle cell lines.
AB  - Transcriptional regulation of smooth muscle cell (SMC) differentiation is a
      rapidly growing area of interest that has relevance for understanding intimal
      disease. Despite the wealth of data accumulating in vitro, however, no study has
      compared the cell-specific marker profile, transfectability, promoter activity,
      and growth characteristics among several SMC culture systems. Accordingly, we
      performed a comprehensive analysis of the marker profile, growth properties,
      transfectability, and SMC promoter activity in four rat SMC lines (A7r5, adult
      and pup aortic, and PAC1). Despite alterations in chromosomal number and
      structure, A7r5, adult aortic, and PAC1 cells express all SMC markers studied
      including SM alpha-actin, SM calponin, SM22, tropoelastin, and to a lesser
      extent, SM myosin heavy chain (SMMHC). In contrast, pup aortic cells express very
      low or undetectable levels of all the above markers except tropoelastin. Adult
      aortic, pup, and PAC1 cells display similar growth curves and levels of proto
      oncogene transcripts, whereas those in the A7r5 line are comparatively less. All
      cell lines studied except pup cells show expression of SMC differentiation genes
      during active growth, indicating that growth and differentiation are not mutually
      exclusive in cultured smooth muscle. Transfection studies reveal dramatic
      differences in DNA uptake and SMC-restricted promoter activity between cell
      lines. Collectively, these results provide detailed information relating to SMC
      molecular biology in culture that should facilitate the selection of a cell line
      for studying the transcriptional regulatory mechanisms underlying SMC
      differentiation.

PMID- 9557941
TI  - Ligand-dependent and -independent interactions with the transforming growth
      factor type II and I receptor subunits reside in the aminoterminal portion of the
      ectodomain of the type III subunit.
AB  - The type III receptor for transforming growth factor beta (TGFbeta), which
      exhibits no kinase activity, binds TGFbeta1 and TGFbeta2 and is involved in
      assembly and activity of the multi-subunit TGFbeta signal transduction complex.
      Recently we showed that TGFbeta receptor type III (TbetaRIII) can participate in
      a complex composed of the dimeric TGFbeta ligand and a type III, II, and I
      receptor subunit. The interaction of the TbetaRIII subunit with TbetaRII is
      TGFbeta-dependent, whereas interaction with TbetaRI is TGFbeta-independent. Here
      we use coexpression of the three types of TGFbeta receptors in baculoviral
      infected insect cells to determine which parts of the unglycosylated TbetaRIII
      receptor participate in the binding of TGFbeta, the TGFbeta-dependent interaction
      with TbetaRII and the TGFbeta-independent interaction with TbetaRI. The results
      suggest that the first 500 amino acid residues in the aminoterminal portion of
      TbetaRIII exhibit all three properties.

PMID- 9557942
TI  - Application and evaluation of the alamarBlue assay for cell growth and survival
      of fibroblasts.
AB  - Cell proliferation assays are essential to developing an understanding of the
      molecular mechanisms that modulate cell growth and differentiation. In this
      paper, we describe the application of alamarBlue, a new and versatile metabolic
      dye, for the detection of Swiss 3T3 fibroblast proliferation and/or survival. As
      a redox indicator, alamarBlue is reduced by reactions innate to cellular
      metabolism and, therefore, provides an indirect measure of viable cell number.
      Various assay parameters were optimized for a 96-well format to achieve a
      detectable range of fibroblast cell number from 100 to 20,000 cells/well, which
      is similar to that obtained with traditional (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) and [3H]thymidine assay techniques. Standard
      (reference) curves generated with a known fibroblast stimulator were used to
      facilitate quantitation and comparison of unknown test substances. The alamarBlue
      assay offers the advantages of technical simplicity, freedom from radioisotopes,
      versatility in detection, no extraction, and excellent reproducibility and
      sensitivity. We anticipate that this simple and versatile alamarBlue assay, when
      used alone or in conjunction with other bioassays, will be a useful tool for
      investigating the complex mechanisms of cellular proliferation.

PMID- 9557944
TI  - Effects of H2O2 on the growth, secretion, and metabolism of hybridoma cells in
      culture.
AB  - The effect of low concentrations of hydrogen peroxide (H2O2) (5 x 10(-7)-9.5 x
      10(-7) M) on cell growth and antibody production was investigated with murine
      hybridoma cells (Mark 3 and anti-hPL) in culture. Cell growth, measured by flow
      cytometry with morphological parameters, was significantly stimulated by H2O2 (8
      x 10(-7) M) but H2O2 concentration of 7 x 10(-6) M and above increased cell
      death. H2O2 stimulation of antibody production was nonsignificant. The metabolism
      of cells treated with 8 x 10(-7) or 1 x 10(-5) M H2O2 was similar to that of the
      control in terms of glucose and glutamine consumption, lactate and ammonia
      production, and amino acid concentrations in the medium. The concentrations of
      lactate dehydrogenase, a marker of cell death, in test and control cells were
      similar. However, concentrations of intracellular free radicals measured by flow
      cytometry with dihydrorhodamine 123 (DHR 123) and dichlorofluorescein diacetate
      (DCFH-DA) as fluorochromes were different. The reactive oxygen species content of
      cells in 8 x 10(-7) M H2O2 was similar to that of the controls, but there was a
      sudden, marked production of superoxide anions (detected with DHR 123) and H2O2
      or peroxides (detected with DCFH-DA) by cells incubated with 1 x 10(-5) M H2O2
      which increased with increasing H2O2 until cell death.

PMID- 9557943
TI  - Maturation-dependent gene expression in a conditionally transformed liver
      progenitor cell line.
AB  - We have isolated a conditionally transformed liver progenitor cell line with
      phenotypic similarities to both hepatoblasts (bipotent embryonic liver cells that
      give rise to hepatocytes and intrahepatic biliary epithelial cells) and liver
      epithelial cells (primitive hepatic cells isolated from adult livers capable of
      generating both hepatocytic and biliary lineages). Cell line L2039 was derived
      from E14 fetal mouse liver after transformation with temperature-sensitive SV-40
      large T antigen. At 33 degrees C, these cells have an epithelial morphology with
      a high nucleocytoplasmic ratio and express both hepatocytic and biliary genes,
      including albumin, alpha-fetoprotein, glutamine synthetase, insulinlike growth
      factor II receptor, fibronectin and laminin, and cytokeratins 8 and 19, a set of
      markers characteristic for hepatoblasts. The presence of cytokeratin 14,
      vimentin, and several oval-cell antigens link cell line L2039 to nonparenchymal
      liver epithelial cell populations thought to contain progenitor cells. Serum
      free, hormonally defined media conditions and extracellular matrix requirements
      were determined for growth and differentiation of this cell line. During culture
      on type IV collagen at 39 degrees C, L2039 cells cease dividing and demonstrate
      hepatocytic differentiation with the assumption of a hepatocytelike morphology
      and glucocorticoid-dependent regulation of liver-specific genes, including
      albumin, alpha-fetoprotein, phosphoenolpyruvate carboxykinase, and liver-enriched
      transcription factors. The number of albumin-positive cells increases during
      culture at 39 degrees C, indicating that L2039 cells convert from a
      prehepatocytic to a hepatocytic phenotype. Under conditions specific for
      hepatocytic differentiation, C/EBPs were expressed and differentially regulated,
      with C/EBPbeta and C/EBPdelta upregulated early and C/EBPalpha only slightly
      expressed after 7 d, indicating that C/EBPalpha may not be a crucial factor in
      commitment to the hepatocytic phenotype.

PMID- 9557945
TI  - Prostaglandins act as neurotoxin for differentiated neuroblastoma cells in
      culture and increase levels of ubiquitin and beta-amyloid.
AB  - Although chronic inflammatory reactions have been proposed to cause neuronal
      degeneration associated with Alzheimer's disease (AD), the role of prostaglandins
      (PGs), one of the secretory products of inflammatory reactions, in degeneration
      of nerve cells has not been studied. Our initial observation that PGE1-induced
      differentiated neuroblastoma (NB) cells degenerate in vitro more rapidly than
      those induced by RO20-1724, an inhibitor of cyclic nucleotide phosphodiesterase,
      has led us to postulate that PGs act as a neurotoxin. This study has further
      investigated the effects of PGs on differentiated NB cells in culture. Results
      showed that PGA1 was more effective than PGE1 in causing degeneration of
      differentiated NB cells as shown by the cytoplasmic vacuolation and fragmentation
      of soma, nuclei, and neurites. Because increased levels of ubiquitin and beta
      amyloid have been implicated in causing neuronal degeneration, we studied the
      effects of PGs on the levels of these proteins during degeneration of NB cells in
      vitro by an immunostaining technique, using primary antibodies to ubiquitin and
      beta-amyloid. Results showed that PGs increased the intracellular levels of
      ubiquitin and beta-amyloid prior to degeneration, whereas the degenerated NB
      cells had negligible levels of these proteins. These data suggest that PGs act as
      external neurotoxic signals which increase levels of ubiquitin and beta-amyloid
      that represent one of the intracellular signals for initiating degeneration of
      nerve cells.

PMID- 9557946
TI  - Molecular models of two competitive inhibitors, IL-2delta2 and IL-2delta3,
      generated by alternative splicing of human interleukin-2.
AB  - Molecular models of IL-2delta2 and IL-2delta3, two alternative splice variants of
      human IL-2 without exon 2 and 3, respectively, are described. These alternative
      splice variants attract particular interest as potential competitive inhibitors
      of the cytokine. Tertiary structure of IL-2 consists of four-helix bundle
      including helices A, B, C and D and a beta-pleated sheet. Exon 2 encodes the A-B
      loop (Asn30-Lys49 residues) linking helices A and B running in one direction.
      Rotation of the helix A around putative centre during the construction of IL
      2delta2 model have not produced any significant changes in the hydrophobic core
      of IL-2 molecule. However, a large hole was formed on the surface of IL-2delta2
      molecule instead of A-B loop in IL-2 fold. A high affinity IL-2 receptor is
      formed by combination of alpha, beta, and gamma(c) chains. Comparison of the
      model of the receptor bound IL-2 with the model of IL-2delta2 has shown that
      their beta-chain binding sites have minimum differences as distinct from alpha
      and gamma(c) chain-binding sites. Exon 3 encodes Ala50-Lys97 fragment which forms
      helices B and C with their short connecting loop. Model IL-2delta3 consists of
      helices A and D and long linking loop. This loop was composed of A-B and C-D
      loops which run in opposite directions in IL-2 structure and contain beta-strands
      making a beta-pleated sheet. Conformation of the linking loop relatively to
      helices A and D was stabilized by creation of a disulphide bond between cysteines
      105 and 125. In addition, the hydrophobic residues of beta-sheet interact with
      the hydrophobic surface of A-D helical complex and close the latter from contacts
      with solution. Comparison of the model of IL-2 bound to receptor with IL-2delta3
      model has shown that absence of helices B and C in IL-2delta3 model results in
      insignificant conformational changes only in residues interacting with gamma(c)
      chain of the receptor. The beta/gamma(c) heterodimer is an intermediate affinity
      receptor of IL-2. Most likely, both IL-2delta2 and IL-2delta3 are naturally
      occurring IL-2 antagonists since they keep the ability of binding with an
      intermediate affinity receptor of this cytokine and fail to engage the alpha
      chain of its high affinity receptor.

PMID- 9557947
TI  - Human extracellular proteins display a different pattern of local sequence
      similarity with the four classes of human T-cell receptor V-regions than foreign
      proteins and human intracellular proteins: a preliminary report.
AB  - A pool of 110 randomly selected/generated amino acids sequences was used to
      perform specific local sequence similarity alignment analysis with the pool of
      279 reported sequences of human T-cell receptor (TCR) V-regions. The 110 analyzed
      sequences were divided, according to their origin and nature, into six protein
      groups, as: human intracellular (hi), extracellular/transmembrane (he) and
      extracellular adhesive matrix (ha) proteins, 'average' human proteins (hum),
      proteins of non-human origin (nhum) and randomly generated quasi-protein
      sequences (r). These sequences were decomposed into all their overlapping 11-mer
      segments, generating a total of 56,836 derived peptides (at least 8000 per
      group). Each derived peptide was aligned with the 279 human TCR V-regions and
      assigned to the category (alpha-like, beta-like, gamma-like or delta-like)
      corresponding to the class (V alpha, Vbeta, Vgamma or Vdelta) of the V-region
      encompassing the most similar segment, as determined by the performed similarity
      search. The six protein groups were found to differ significantly in their
      distribution of derived peptides among the four categories. According to the
      binomial tests results, human proteins from the extracellular compartment (he,
      ha) comprise a higher proportion of delta-like segments (P = 2.3 x 10(-2) and P <
      10(-8), respectively) than the 'average' human proteins (hum). In addition, and
      in accordance with this finding, proteins that are normally not found in that
      topological compartment comprise a lower proportion of delta-like peptides (P =
      1.4 x 10(-5) and P < 10(-8) for groups nhum and hi, respectively) than the
      'average' human proteins (hum). In contrast, these proteins comprise a higher
      proportion of gamma-like segments (P = 8.3 x 10(-3), P = 1.4 x 10(-3) and P = 1.7
      x 10(-4), for groups r, nhum and hi, respectively) than the 'average' human
      proteins (hum). These findings indicate significant differences between proteins
      encountered in the extracellular compartment--that are normally immunologically
      tolerated--and those the presence of which is usually non-tolerated. The results
      suggest that the discrimination and the reaction of the human immune network to
      proteins found in the extracellular compartment correlate with the proteins'
      pattern of preferential local sequence similarity with the Vgamma and Vdelta
      classes of human TCR V-regions, implying a specific and an important role of
      gammadelta-cells in the maintenance of the immune homeostasis. Whether this
      implication represents a rule associated with self-tolerance, will be
      investigated by future analyses.

PMID- 9557948
TI  - Effect of PGE2 on the cell surface molecule expression in PMA treated thymocytes.
AB  - PGE2 is produced by cells of the thymic microenvironment. The effects of PGE2 are
      mediated by cAMP through binding to its intracellular receptor protein kinase A
      (PKA). Phorbol 12-myristate 13-acetate (PMA) is known to modulate CD molecule
      expression on thymocytes, probably through activation of protein kinase C (PKC).
      We have hypothesized that cross-talk between these two signalling pathways may
      affect modulation of the CD molecules on the cell surface of thymocytes. For this
      purpose, we compare the effects of PMA alone or combined with PGE2 on CD3, CD4
      and CD8 expression on mouse thymocytes by flow-cytometric analysis. PMA treatment
      almost completely abolished CD4 expression and slightly decreased CD3 and CD8
      expression. PGE2 alone did not change the CD3, CD4 and CD8 molecule expression.
      Combined with PMA, PGE2 can overcome the decrease induced by PMA of the CD3
      expression and partially reduced the disappearance of the CD4 molecule. On the
      other hand PGE2 accelerated the loss of CD8 molecule expression. These events
      occurred only in CD4+ CD8+ immature thymocytes. An analogue of cAMP (dibutyryl
      cAMP) mimics the effect of PGE2, but not Br-cGMP. This differential regulation by
      PGE2 of the CD molecule expression on immature thymocytes may provide additional
      evidence on the role of PGE2 during the process of thymic differentiation.

PMID- 9557949
TI  - Activation of influenza-specific memory cytotoxic T lymphocytes by Concanavalin A
      stimulation.
AB  - Traditionally, the in vitro activation of virus-specific memory cytotoxic T
      lymphocytes (CTLs) has been achieved by stimulating the CTLs with antigen
      presenting cells (APCs) infected with an appropriate virus or pulsed with virus
      specific antigenic peptides. Here, we describe the utilization of the polyclonal
      activator Concanavalin A (ConA) for in vitro restimulation of memory CTLs from
      virus-primed mice. Using this simple method, the activation of splenocytes with
      ConA for 3 days (i) eliminates the need to stimulate with virus-pulsed APCs and
      (ii) generates CD8+ CTLs that exhibit virus specificity and MHC-restricted lytic
      activity similar to CTLs obtained by conventional viral restimulation. In vitro
      ConA stimulation of splenocytes from BALB/c mice primed with the A/Texas/77 or
      A/Japanese/57 strain of influenza virus and from C57L/J mice infected with the
      A/Texas strain, generated CTLs with specific lytic activity. Hence reactivation
      of memory CTLs by this method is a general phenomenon rather than a mouse or
      viral strain-specific one. The ConA stimulation method used here had a recall of
      long-term (1 year) memory CTLs that effectively lysed virally infected targets.
      Further ConA-stimulated effector lymphocytes from virally primed animals have
      been shown to recognize and subsequently lyse target cells pulsed with virus or
      virus-derived peptides. The ConA reactivation of specific anti-viral CTLs may
      facilitate (i) studying anti-viral CTL responses and (ii) identifying of viral
      epitopes when unknown or when appropriate viral stimulation is impossible.

PMID- 9557950
TI  - Purification and characterization of lipopolysaccharide induced TNF-like factor
      from rabbit serum.
AB  - A TNF-like factor was purified from lipopolysaccharide (LPS) induced New Zealand
      white rabbit serum. The TNF-like factor was purified by DEAE-Sephacel, Sephacryl
      S-200, Mono-Q, CM-affi gel Blue, Superose 12 H/R preparative columns to the
      specific activity of 4 x 10(6) U/mg protein. The purified protein was 45 kDa in
      its oligomeric form and 22 kDa in its monomeric form. Rabbit TNF-like factor had
      a pI value of 5.0 and was resistant to trypsin digestion. The TNF-like factor
      reacted with polyclonal-Ab against human TNFalpha on immunoblot and
      immunoprecipitation analysis and interacted with human TNF receptors. Taken
      together, rabbit TNF-like factor might be a high molecular weight form of rabbit
      TNFalpha.

PMID- 9557951
TI  - Signalling initiated with CD4-TCR or TCR-TCR interactions: comparison of tyrosine
      phosphorylation patterns and CD45 effects.
AB  - Antigen-triggered response in T cells is mediated by the T cell receptor
      (TCR)/CD3-complex. This signalling, however, is modulated by a number of other
      surface molecules. Among the most important of these is the CD4/CD8 molecule
      which associates with the TCR/CD3-complex and binds to the MHC complex. The
      molecular mechanisms involved in interactions between TCR-TCR and TCR-CD4 are not
      fully understood. We have earlier described an experimental model that allows us
      to dissect signals involving CD4-TCR interactions and those involving TCR-TCR
      interactions using a mouse CD4-CD8- T cell hybridoma cell-line transfected either
      with the TCR from a mouse T-helper 2 cell-line (D10) alone or with both the TCR
      and the CD4 molecule. To further characterize these two different modes of
      signalling in T lymphocytes we have studied the tyrosine phosphorylation patterns
      resulting from these interactions. In addition, we have studied the modulatory
      effect of the CD45 molecule on these interactions. In contrast to some earlier
      reports, we found that both the patterns of induced tyrosine phosphorylation and
      the effects of CD45 modulation were essentially similar in the CD4-TCR and the
      TCR-TCR signal transduction cascades. The results are consistent with a purely
      synergistically amplifying function for CD4 on the TCR-mediated signalling.

PMID- 9557952
TI  - Nucleotide sequence analysis of a human monoclonal antibody 22-13 reactive with
      lung tumor-associated antigen.
AB  - A human monoclonal antibody (HuMAb) 22-13 (IgG1, kappa) recognizes a cytoplasmic
      antigen associated primarily with human lung tumors. This study reports the
      primary nucleotide and deduced amino acid sequences of the rearranged heavy and
      light chains of the HuMAb 22-13. This HuMAb uses a VH gene member of the V(H)Ia
      gene family, 51P1 and is productively rearranged with a D-D fusion product of the
      D(LR)2 and D(XP)2 germ line DH genes and the germ line JH3 gene. HuMAb 22-13
      Vkappa belongs to the kappa light chain variable subgroup IIIb family and appears
      to be derived from the Humkv325 germ line gene and is rearranged with a germ line
      Jkappa5 gene. The results reveal that production of a HuMAb 22-13 is achieved by
      rearrangement of the 51P1/Humkv325 germ line variable region gene combination,
      associated with the autoimmune repertoire and that HuMAb 22-13 has a striking
      sequence homology to rheumatoid factors (RFs) of the Wa idiotypic family. HuMAb
      22-13 and Wa RFs have in common V(H)Ia and VkappaIIIb gene segments, but use
      different DH, JH and Jkappa gene segments. However, in spite of this structural
      similarity, HuMAb 22-13 does not display rheumatoid factor activity. Taken
      together with the reported findings, these data indicate the representation of
      the shared usage of highly homologous variable region genes in entirely different
      humoral immune responses in the human system.

PMID- 9557953
TI  - Antibody reactivity to conserved linear epitopes of Plasmodium falciparum
      erythrocyte membrane protein 1 (PfEMP1).
AB  - The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of
      protein antigens are involved in adhesion of P. falciparum infected erythrocytes
      to the capillary endothelium of the host. Antibodies to variable regions of these
      proteins, measured by agglutination, correlates with clinical protection against
      falciparum malaria. In this study we investigated the occurrence of antibodies to
      conserved sequences of these very variable proteins in a population living in an
      area endemic for falciparum malaria. Using the ELISA method, we were able to
      measure an antibody response to three synthetic peptides derived from conserved
      regions of PfEMP1. The antibody responses to these peptides increased with age
      and were higher in individuals with asymptomatic P. falciparum infection compared
      to individuals presenting with fever attributable to falciparum malaria. This
      indicates that antibodies recognising the conserved regions of PfEMP1 arise upon
      exposure to the parasite, and that these may be involved in the development of
      protection against malaria. Antibodies to the Pfalhesin peptide of the human
      aniontransporter, band3, were measured by the same method. The magnitude of this
      antibody response did not correlate with neither age nor clinical protection.

PMID- 9557954
TI  - A hemagglutinin-based multipeptide construct elicits enhanced protective immune
      response in mice against influenza A virus infection.
AB  - Multipeptide constructs, comprising adjacent sequences of the 317-341
      intersubunit region of immature influenza A hemagglutinin (H1N1), were designed
      and the functional properties of these branched peptides were compared to that of
      the corresponding linear peptides. In vivo studies revealed that the
      immunogenicity of the peptides was dependent on the presence of the hydrophobic
      fusion peptide (comprised in FP3), encompassing the N-terminal 1-13 sequence of
      the HA2 subunit. Antibody and T cell recognition, however, was directed against
      the 317-329 HA1 sequence, comprised in the P4 peptide. Multiple copies of P4,
      covalently linked by branched lysine residues, significantly enhanced the
      efficiency of antibody binding and the capacity of peptides to elicit B- and T
      cell responses. A fraction of peptide induced antibodies reacted with immature or
      with proteolitically cleaved hemagglutinin (HA) molecules pretreated at low pH.
      Immunization with a multipeptide construct, (P4)4-FP3, not only resulted in
      elevated antibody and T cell responses but conferred enhanced protection against
      lethal A/PR/8/34 (H1N1) infection as compared to its subunit peptides. The
      beneficial functional properties of this artificial peptide antigen may be
      acquired by multiple properties including: (i) stabilized peptide conformation
      which promotes strong, polyvalent binding to both antibodies and MHC class II
      molecules; (ii) appropriate P4 conformation for antibody recognition stabilized
      by the covalently coupled fusion peptide, resulting in the production of virus
      cross reactive antibodies which inhibit the fusion activity of the virus; (iii)
      activation of peptide specific B cells which potentiate antigen presentation and
      peptide specific T cell responses; and (iv) generation of helper T cells which
      secrete lymphokines active in the resolution of infection.

PMID- 9557955
TI  - Lack of IL-1 receptor antagonistic activity of the capsular F1 antigen of
      Yersinia pestis.
AB  - Because capsular F1 antigen of Yersinia pestis is reported to share sequence
      homology with interleukin-1 receptor antagonist (IL-1ra), we investigated the
      potential IL-1 receptor antagonistic activity of F1 on human endothelial cells
      (EC). The biological activities of IL-1 receptor antagonist (IL-1ra) or IL-1ra
      like molecule were measured by its ability to suppress the IL-1beta-mediated
      induction of adhesion molecules (ICAM and ELAM) on EC and of IL-6 secretion by
      these cells. Two different, purified, immunogenic and biologically active
      preparations of F1, at concentrations up to 10-fold higher than that of IL-1ra,
      did not exhibit any inhibitory activities of IL-1ra. These F1 preparations also
      did not activate peripheral blood mononuclear cells to produce IL-4 or IL-10,
      cytokines which might downregulate pro-inflammatory cytokine production in
      response to infection. Thus, even though there is a high degree of similarity
      between F1 antigen and IL-1ra in three-dimensional structure by computer modeling
      and sequence homology, our work indicates that F1 antigen of Y. pestis does not
      have IL-1ra-like activity.

PMID- 9557956
TI  - Cytokines serum levels as the markers of thyroid activation in Graves' disease.
AB  - In order to examine which cytokine could be used as a marker of the biological
      effect of thyroid hormones or anti-thyroid antibodies in Graves' disease (GD)
      patients, we simultaneously evaluated the concentrations of TSH, free thyroid
      hormones (fT3 and fT4), anti-thyroid antibodies (anti-TPO and anti-TG) and a
      group of cytokines: interleukin-2 (IL-2), tumour necrosis factor alpha
      (TNFalpha), interleukin-6 (IL-6) and their soluble receptors (sIL-2R, sTNFalphaR,
      sIL-6R) as well as interleukin-10 (IL-10) in eight GD females and nine normal
      controls. We found that serum sIL-2R concentrations of GD patients had only the
      tendency to be higher versus controls, but strong positive correlations between
      fT3 and fT4 and sIL-2R in peripheral blood of GD subjects were revealed. We
      showed that sIL-2R was the best cytokine marker, showing very good correlation
      with the endocrine status of GD patients.

PMID- 9557957
TI  - Oral administration of one dose of cholera toxin induces a systemic immune
      response prior to a mucosal immune response by a direct presentation in the
      spleen.
AB  - In the present report the results indicate that the oral administration of one
      dose of CT in rats results in an antibody immune response in the spleen 48 h
      later, whereas no antitoxin antibody forming cells were found in the Peyer
      patches (PP), mesenteric lymph node (MLN) and lamina propria (LP) of the small
      intestine. At this time the main isotype of the antitoxin antibodies in the
      spleen were IgG and IgM, 5 days after the priming, few antitoxin AFC were
      observed in the MLN, IgG being the main isotype, whereas no IgM antitoxin AFC
      were found. At 1 week after priming the number of antitoxin AFC in the MLN
      reached similar values to those observed in the spleen. When cells from the
      spleen of rats primed orally with one dose of CT were cultured during 4 days in
      the presence of inhibitory doses of anti-Ia MAb (OX6), the number of antitoxin
      AFC was diminished when compared with that observed when cells were cultured in
      the absence of anti-Ia. The main isotype of antitoxin AFC observed when cells
      were analyzed after culture was IgM and it was the isotype most affected by the
      treatment with MAb anti-Ia. These results strongly suggest that an in situ
      presentation of the antigen did occur in the spleen. On the other hand, when the
      secondary immune response was studied 48 h after boosting, antitoxin AFC were
      found in the PP, MLN, SP and LP and 5 days after the booster a 20-30-fold
      increase was observed in all lymphoid tissues studied, indicating that the
      secondary immune response found in the spleen was mainly due to the recruitment
      of memory cells from Peyer's patches. However, when spleen cells were cultured 48
      h after the immunization in the presence of inhibitory doses of anti-Ia a little
      decrease in the number of AFC was observed when compared with the controls (in
      absence of anti-Ia). The analysis of the antitoxin antibodies in sera and
      intestinal fluids were in line with the results presented above. The results
      shown in this report indicate that the systemic immune response observed after
      the oral administration of CT could be due in part to an in situ presentation of
      the antigen in the systemic compartments, especially in the spleen.

PMID- 9557959
TI  - Molecular cloning of the cDNA encoding the constant region of the immunoglobulin
      A heavy chain (C alpha) from a marsupial: Trichosurus vulpecula (common brushtail
      possum)
AB  - A cDNA encoding the brushtail possum immunoglobulin A heavy chain constant region
      (C alpha) was isolated by screening a mesenteric lymph node cDNA library with a
      porcine C alpha exon 3 probe. The larger of the two positive clones isolated
      (Tv4a) consisted of 1325 bp of possum cDNA that included an open reading frame of
      1191 bp. Its deduced amino acid sequence had a high degree of sequence identity
      with known eutherian C alpha sequences. This clone appears to encode the entire
      possum IgA heavy chain constant region. The possum C alpha sequence had a
      nucleotide sequence identity of 57.7% with porcine C alpha, 51% with mouse C
      alpha, 46.7% with dog C alpha and 45.9% with human C alpha2. The corresponding
      amino acid identities were 46.7, 45.6, 49.4 and 49%, respectively.

PMID- 9557958
TI  - A fetal sheep liver extract reverses age-related increments in spontaneous and
      induced cytokine production by indirect environmental effects.
AB  - BALB/c, DBA/2 and C57BL/6 mice of different ages (ranging from 8 to 110 weeks of
      age) were used as spleen cell donors to assay cytokine production from ConA
      activated spleen and Peyer's Patch (PP) lymphocytes. As reported in an earlier
      publication, there was an age-related decline in IL-2 production in all strains,
      with a general increase in IL-4 and IL-10 production with age, this being
      particularly marked for PP cell preparations. Similar conclusions were reached
      from independent analysis of CD44hi and CD44lo cell populations in these groups
      (memory vs. naive cells, respectively). Interestingly, IL-6 production was
      dramatically increased (some 4-5-fold in the different strains) and significantly
      increased levels of IL-6 were detected in the serum of aged mice. A previously
      described sheep fetal liver extract was able to reverse, to varying degrees,
      these cytokine changes associated with aging. Interestingly, when cells from aged
      mice were adoptively transferred to lethally irradiated young (8 week)
      recipients, the cytokine production phenotype of cells harvested from recipient
      mice 3 weeks later was that of the aged donor, unless recipients were treated
      continually with extract. Treatment of the donor alone produced minimal changes
      in cytokine production 3 weeks following adoptive transfer. The effect of extract
      was reversed in treated aged mice by concomitant daily intravenous infusion of
      the competitive inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine
      (NMMA)), which also decreased the increased serum nitrate levels in mice treated
      with extract. Our data suggest an important role for reactive nitrogen products,
      themselves induced by fetal liver extract, in age-associated changes in cytokine
      production.

PMID- 9557960
TI  - Enhanced prevalence of T cells expressing TCRBV8S2 and TCRBV8S3 in hearts of
      chronically Trypanosoma cruzi-infected mice.
AB  - We have analysed the relative T cell receptor (TCR) BV gene usage in T cells from
      hearts and spleens of CBA/HJ mice chronically infected with the Tulahuen strain
      of Trypanosoma cruzi. During chronic infection, CBA/HJ mice recruit T cells at
      the major site of inflammation (i.e. the heart), with over-representation of
      certain TCRBV gene subfamilies (TCRBV8S2 and TCRBV8S3). In contrast, no signal or
      a very weak message from a limited number of T cells was recorded from one heart
      of the control group. No alteration of TCRBV distribution was recorded in spleens
      of chronically infected CBA/HJ. Our findings indicate that there is a
      preferential TCRBV gene usage in the T cell response in the hearts of chronically
      infected mice. Furthermore, the pattern of CDR3 lengths in inflammatory T cells
      was altered.

PMID- 9557961
TI  - Association of viral load in plasma samples of HIV-infected hemophilia patients
      with autoantibodies and gp120-containing immune complexes on CD4+ lymphocytes.
AB  - OBJECTIVE: We investigated whether the induction of antilymphocyte autoantibodies
      and immune complexes is associated with the activity of HIV replication. METHODS:
      Viral HIV-1 RNA was measured in the plasma samples of 84 HIV+ hemophilia patients
      and correlated with the IgM, IgG, IgM/IgG and IgM/IgG/gp120 load of circulating
      CD4+ lymphocytes, CD4+ and CD8+ cell counts, plasma neopterin levels and in vitro
      T-cell responses to mitogens and pooled allogeneic stimulator cells. RESULTS:
      Compared to patients with no immune complexes, on circulating CD4+ lymphocytes,
      viral load was increased in patients with IgM, IgM/IgG or IgM/IgG/gp120
      complexes. Sequential analysis of HIV+ patients showed that peaks of retroviral
      activity were associated with the subsequent formation of CD4+ lymphocyte
      reactive IgM and IgG autoantibodies and gp120-containing immune complexes.
      CONCLUSION: The induction of autoantibodies and immune complexes attached to CD4+
      lymphocytes is associated with periods of increased viral activity in HIV
      infected patients.

PMID- 9557962
TI  - Effects of some antigenic fractions of Leishmania major on nitric oxide
      production and IL-12 secretion by murine peritoneal macrophages.
AB  - Nitric oxide (NO) and IL-12 are important mediators of the immune response to
      Leishmania major. In this study, the effects of L. major promastigotes, crude
      antigenic fraction (CAF) and its subfractions on NO production and IL-12
      secretion by BALB/c mice peritoneal macrophages is investigated. The subfractions
      of CAF, namely, fractions 1, 2 and 3, that were in the molecular weight range of
      97.4-66, 66-45 and below 45 kDa, respectively, were separated by SDS-PAGE. NO
      production was determined by using Griess reagent and IL-12 was measured by
      ELISA. It was found that NO production was stimulated by promastigotes but not by
      CAF or its subfractions. IL-12 secretion was stimulated by promastigotes, CAF and
      fraction 1 while fractions 2 and 3 did not have any effect.

PMID- 9557963
TI  - Class II MHC antigen-expressing cells in the pulp tissue of human deciduous teeth
      prior to shedding.
AB  - The distribution and ultrastructure of the class II major histocompatibility
      complex (MHC) antigen-expressing cells in the pulp tissue of human deciduous
      teeth during the process of physiological root resorption was surveyed by
      histochemical and immunocytochemical methods using an anti-human leukocyte
      antigen (HLA)-DR-monoclonal antibody. Dental pulp was found to contain numerous
      HLA-DR-positive cells of various shapes; those showing a dendritic appearance
      were located mainly in the periphery of the pulp tissue, associated closely with
      the odontoblasts. The immunopositive cells sometimes extended their cytoplasmic
      processes into the dentinal tubules and increased in number in the areas affected
      by dental caries, attrition or restorative procedures, implicating their role in
      immunosurveillance. The immunopositive cells were located consistently at the
      pulp-dentin border during the stage of active resorption, adjacent to the
      preodontoclasts or odontoclasts, and covered the exposed dentin surface after the
      detachment of the odontoclasts until the onset of cementum formation. These data
      suggest that the HLA-DR-immunopositive cells in the coronal pulp of human
      deciduous teeth play an inductive role in the differentiation, migration and/or
      activation of the odontoclasts and cementoblast-like cells during the stages of
      tooth resorption.

PMID- 9557964
TI  - Immunohistochemical localization of vascular endothelial growth factor in the
      endocrine glands of the rat.
AB  - Vascular endothelial growth factor (VEGF) is a secreted polypeptide with specific
      effects on endothelial cell growth and vascular permeability. While previous
      studies have focused on the expression of VEGF associated with angiogenesis in
      tumor and embryonal tissues, little is known about the role of VEGF in normal
      adult tissues. In the present study, a specific antibody was used to study the
      immunohistochemical localization of VEGF in the entire body of normal adult rats.
      Intense to moderate immunoreactivities for VEGF were detected in some endocrine
      cell types, namely, the parafollicular cell of thyroid gland, B cell of endocrine
      pancreas, N cell of adrenal medulla and a minority of the thyrotrophs of the
      pituitary gland. A certain exocrine cell type, i.e., the surface mucous cell of
      stomach, was also immunoreactive for VEGF. At the ultrastructural level, VEGF
      immunoreactivity was localized exclusively in the secretory granules of all
      immunopositive endocrine and exocrine cells examined. The present study provided
      immunohistochemical evidence for the occurrence of VEGF in subsets of endocrine
      and exocrine cells of normal adult rats, suggesting that these secretory cells
      regulate local vascular permeability through a paracrine action of VEGF.

PMID- 9557965
TI  - Ultrastructural changes of the myoepithelium of the dilator pupillae during
      miosis and mydriasis in the rat iris.
AB  - Changes in the three-dimensional structures of the myoepithelium of the dilator
      pupillae (MDP) during mydriasis and miosis were investigated in the rat by
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
      Following fixation, SEM specimens were treated with sodium hydroxide to expose
      the muscle surface. Significant morphological differences were noted in the
      anterior surface of the MDP between mydriasis and miosis. In the mydriatic eye, a
      highly rugged structure with numerous linear folds was oriented circularly or
      obliquely together with spherical bulges. These structures, presumably
      corresponding to the highly contractile portion of the myoepithelial cells, were
      more prominent near the pupillary margin than near the ciliary margin, indicating
      that the MDP may contract much more strongly in the pupillary margin. In the
      miotic eye, the anterior surface of the MDP showed less conspicuous linear folds
      in the pupillary area, and was almost flat in the ciliary area. Radially oriented
      ridges were observed only in the pupillary area. These findings suggest that the
      contraction of the sphincter pupillae in miosis induces a stretching of the MDP
      toward the pupil and a circular shrinkage of the MDP. Ultrastructural changes of
      the MDP particularly near the pupillary margin may play an important role in
      regulation of the pupil diameter as a diaphragm of the eye because morphological
      changes such as the linear folds, spherical bulges, and ridges were more
      prominent near the pupillary margin than those near the ciliary margin.

PMID- 9557966
TI  - Fine structure of the tongue and lingual papillae of the penguin.
AB  - The tongue in four species of penguin was investigated by light microscopy and by
      scanning electron microscopy, with special reference to the lingual papillae. 1)
      The middle of the penguin tongue contains a pair of long cartilages and long
      tendons accompanied by striated muscle bundles. 2) Large, spine-like, and
      caudally directed lingual papillae (filiform-like papillae) densely cover the
      dorsal surface of the tongue, apparently serving to catch fishes. 3) By light
      microscopy, the dorsal lingual epithelium with the lingual papillae are seen as a
      thick cornified layer, but the lateral and lower surfaces have a thinner
      cornified layer. 4) The connective tissue core (CTC) under the epithelium of the
      lingual papilla shows a stereo structure similar to but smaller than the external
      form of the papilla. The CTC contains some blood vessels and nerve fibers; the
      lingual glands are found in the submucous layer only in the posterior tongue. 5)
      Bundles of nerve fibers in the lamina propria of the tongue were
      immunohistochemically positive for PGP 9.5, and it appeared that Merkel
      corpuscles were distributed in the connective tissue closely beneath the
      epithelium of the finger-like papillae, though they were only weakly
      immunoreactive for PGP 9.5. 6) Numerous fine filaments of elastic fibers are
      found closely beneath the epithelial cell layer of the dorsal surface of the
      tongue including the lingual papillae, while there are very few of them on the
      lateral and lower sides of the tongue.

PMID- 9557968
TI  - Elastic properties of living fibroblasts as imaged using force modulation mode in
      atomic force microscopy.
AB  - Using the force modulation mode in atomic force microscopy, we measured elastic
      properties of living mouse fibroblasts (NIH3T3) in a culture medium. The
      topographic images of the cellular surface and the corresponding elastic images
      of the cellular surface were able to be captured simultaneously with high spatial
      resolution. The consecutive images were useful for examining time-dependent
      changes in the cellular surface. We observed that some cells continued to shrink
      and change their softness for 2 hours. Then the force modulation mode in atomic
      force microscopy shows potential use in analyzing time-dependent regional elastic
      properties of living cells with high spatial resolution.

PMID- 9557967
TI  - Localization of cytoskeletal filaments during membrane rearrangement in rat
      parietal cells stimulated with gastrin.
AB  - When stomachs are stimulated to secrete acid, the intracellular canaliculi of the
      parietal cell increase and there is a concomitant depletion of the cytoplasmic
      tubulovesicular system. This change is believed to occur through the
      transformation of tubulovesicular membranes into intracellular canaliculi. This
      study was undertaken to examine the distribution of the cytoskeletons in rat
      gastric parietal cells during this process. In the resting parietal cells, actin
      filaments decorated with heavy meromyosin (HMM) were found in the cores of
      microvilli, extending from the apex of microvilli into the pericanalicular
      cytoplasm and forming radial networks. In some cases, these actin filaments were
      also associated with the tubulovesicles. Moreover, tubulovesicular membranes were
      rare in the 300 nm zone around intracellular canaliculi but numerous actin
      filaments were seen in this region. Soon after stimulation of the parietal cells
      by gastrin, tubulovesicles were closely associated with the intracellular
      canaliculi, while actin filaments networks adjacent to the canaliculi diminished
      and their labeling with HMM seemed less orderly. By immunocytochemistry,
      immunogold particles indicating ezrin were associated with microvillous membranes
      in the resting as well as stimulated parietal cells but were absent on the
      tubulovesicular membranes. When intermediate filaments were immunocytochemically
      investigated using anti-cytokeratin immunogold particles clearly labeled
      filamentous bundles present around the intracellular canaliculi, perinuclear
      spaces and under the basolateral cell membrane. Their localization was not
      changed after stimulation. These results suggest that actin filaments in the
      cytoplasm around the intracellular canaliculi may play a key role in the
      translocation of the tubulovesicles toward the intracellular canaliculi during
      the acid secreting process.

PMID- 9557969
TI  - Lymphatic network and nerve plexus in the myenteric layer of the monkey jejunum:
      a topographic study using an enzyme-histochemical method.
AB  - The topographic relationship between the lymphatic network and the nerve plexus
      in the myenteric layer of the monkey jejunum was studied by an enzyme
      histochemical method. Identification of the lymphatics was achieved by a 5'
      nucleotidase staining method, and the enteric neural components were visualized
      by acetylcholinesterase staining. A well-developed lymphatic network and a dense
      nerve plexus were demonstrated throughout the myenteric layer. Numerous segments
      of the initial lymphatics, with their blind endings at the apical parts, tended
      to gather toward the ganglion and run along the primary nerve strands. Elements
      of the tissue interstitium separated the lymphatics from the enteric nerves.
      Nerve terminals were often located closely beneath the endothelium of the initial
      lymphatics and were exposed to the subendothelial tissue on the side facing the
      abluminal surface of the lymphatic endothelium. These findings suggest that the
      lymph flow in the initial lymphatics might be regulated by the enteric nervous
      system, and that the transport of tissue fluid by the lymphatics might serve as a
      suitable microenvironment for the enteric nerves.

PMID- 9557970
TI  - Corticosteroids stimulate the differentiation of growth hormone cells but
      suppress that of prolactin cells in the fetal rat pituitary.
AB  - An organ culture study was carried out to examine the effects of adrenal
      corticosteroids on the development of growth hormone (GH) cells and prolactin
      (PRL) cells. The adenohypophysial primordia were separated from 13.5-day-old
      fetal rats and maintained in vitro for 8 days with or without cortisol.
      Immunohistochemical examination of these explants showed that cortisol stimulated
      the differentiation of GH cells but suppressed that of PRL cells in a dose
      dependent manner. In the absence of cortisol there were more PRL cells.
      Corticosterone had a similar effect on the developing adenohypophysis. When the
      pituitary primordia of Day 16.5 were cultured for 5 days and studied by the in
      situ hybridization technique, the expression of GH and PRL mRNA was found to be
      parallel with the immunoreactivity of the respective hormones. These data are
      discussed in relation to the normal development of GH and PRL cells in the fetal
      rat adenohypophysis.

PMID- 9557971
TI  - C-Fos-like immunoreactivity in the upper cervical spinal dorsal horn neurons
      following noxious chemical stimulation of the nasal mucosa in pentobarbital
      anesthetized rats.
AB  - Noxious chemical stimulation of the rat nasal mucosa with mustard oil induces the
      expression of Fos-like immunoreactivity in trigeminal and other brain stem
      neurons which contribute to upper airway protective reflexes such as sneezing,
      coughing and apnea. To examine the role of nociceptive processing in the upper
      cervical spinal cord, we investigated the Fos-like immunoreactivity of the
      brainstem and upper cervical spinal cord following the injection of mustard oil
      (10 microl of 10%) into the nasal mucosa of pentobarbital anesthetized rats. Two
      hours after the application of mustard oil, numerous Fos-immunoreactive neurons
      were found in the mediolateral end of the C1 and dorsolateral division of the C2.
      The mean numbers of the Fos-immunoreactive neurons in the laminae I and II of the
      ipsilateral first and second spinal segments were significantly greater than in
      the control (vehicle treated) rats. There were no significant differences in the
      mean number of Fos-immunoreactive neurons in the contralateral C1 between the
      mustard oil and vehicle-treated rats. These results suggest that the C1-C2 dorsal
      horn neurons process the nociceptive information from nasal mucosa as well as
      other areas innervated by the trigeminal nerves, and that ethmoidal nerves may
      contribute to the exclusive conveyance of nociceptive information.

PMID- 9557972
TI  - Morphodifferentiation of skeletal muscle fiber ends at the myotendinous junction
      in the postnatal Chinese hamster: a scanning electron microscopic study.
AB  - The postnatal morphodifferentiation of muscle fiber ends at the myotendinous
      junction was examined by scanning electron microscopy in gastrocnemius muscles of
      the Chinese hamster. Muscle fiber ends during the first week were simply conical
      or slightly complex, having a few pit-like invaginations and longitudinal and
      narrow clefts. By the second week, fiber ends gradually became complicated with
      an increased number of clefts and finger-like processes. Pits and short clefts
      linearly arranged towards the fiber tip were visible until the second week. This
      possibly indicates the linear elongation of the clefts by the fusion of adjacent
      pits to one another and to preexisting clefts. By the fourth week, the fiber ends
      had almost fully matured and displayed numerous cytoplasmic processes and lateral
      grooves.

PMID- 9557973
TI  - GABAergic projections from the lateral lemniscus to the inferior colliculus of
      the rat.
AB  - The objective of the present study was to provide direct evidence regarding
      GABAergic projections from the nuclei of the lateral lemniscus to the central
      nucleus of the inferior colliculus (ICC), and from the ICC to the opposite ICC.
      Projections of GABAergic neurons in the rat were investigated by a combination of
      fluorogold (FG) retrograde tracing and GABA immunocytochemistry. FG was first
      injected into a frequency-defined region (11-13 kHz) in the center of the ICC,
      and 1-2 weeks was allowed for retrograde transport. Vibratome sections were then
      cut through the brainstem and stained with GABA antibody. Double-labeling was
      taken as evidence of GABAergic neurons projecting to the ICC. The results from FG
      retrograde labeling alone showed that neurons in the dorsal nucleus of the
      lateral lemniscus (DNLL) bilaterally, in the intermediate and ventral nucleus of
      the lateral lemniscus (INLL and VNLL) ipsilaterally, and in the ICC
      contralaterally project to the ICC. GABA immunostaining alone showed substantial
      numbers of GABA positive neurons in the nuclei of the lateral lemniscus and the
      inferior colliculus. FG and GABA double-labeled neurons were present in all
      nuclei of the lateral lemniscus that project to the ICC. The greatest
      concentration of double-labeled neurons was found bilaterally in the DNLL,
      suggesting a prominent GABAergic projection from the DNLL to the ICC. The
      presence of many double-labeled neurons in the ipsilateral INLL and VNLL suggests
      that there are also GABAergic inputs from the INLL and VNLL to the ICC. No double
      labeled neurons were found in the contralateral ICC, which suggests the
      possibility of a prominent non-GABAergic projection.

PMID- 9557974
TI  - Establishment of conditionally immortalized rat utricular epithelial cell lines
      using a retrovirus-mediated gene transfer technique.
AB  - Supporting cells in the inner ear sensory epithelium are most likely hair cell
      progenitors. In an effort to establish an in vitro model system of hair cell
      differentiation, we developed immortalized epithelial cell lines by transferring
      the tsA58 allele of the SV40 large T antigen oncogene into neonatal rat utricular
      supporting cells using a retrovirus. The established cell lines have been stably
      maintained continuously for more than 25 passages and display many features
      similar to primary supporting cells. They grow in patches and assume a polygonal
      morphology. Immunocytochemical characterization of the established cell lines
      reveals that these cells can be labeled by epithelial cell markers, but not by
      fibroblast, glial or neuronal markers. The immortalized cells grow rapidly in
      serum medium at permissive temperature, but the majority cease proliferation when
      cultured in serum free medium at non-permissive temperature. These cells respond
      to mitogenic growth factors including bFGF, EGF and TGF-alpha and express growth
      factor receptors in a manner similar to the primary supporting cells.
      Furthermore, we find that the cells undergo a morphological differentiation when
      cultured in serum free medium at non-permissive temperature in the presence of
      bFGF. Under these conditions, the cells shrink in size, become elongated, and
      express early hair cell markers such as calretinin and calmodulin. The utricular
      epithelial cell line we have established may potentially provide an invaluable
      system for studying hair cell differentiation and regeneration.

PMID- 9557975
TI  - Low intensities and 1.3 ratio produce distortion product otoacoustic emissions
      which are larger in heterozygous (+/dn) than homozygous (+/+) mice.
AB  - The f2/f1 frequency ratio of 1.3 in combination with stimulus levels of L1/L2 =
      50/60 and 50/50 dB SPL produced a higher level of distortion product otoacoustic
      emissions (DPOAE) in the heterozygous (+/dn) mice than in the homozygous (+/+)
      mice. These results suggest that the dn gene carriers have a unique cochlear
      trait which may be related to the dn gene locus and expressed via a frequency-
      and intensity-dependent DPOAE function.

PMID- 9557976
TI  - Changes in cochlear antioxidant enzyme activity after sound conditioning and
      noise exposure in the chinchilla.
AB  - Exposure to low level noise prior to a high level exposure reduces noise-induced
      hearing loss in mammals. This phenomenon is known as sound conditioning or
      'toughening'. Reactive oxygen intermediates have been implicated in noise-induced
      cochlear damage. To evaluate if in situ antioxidant processes may play a role in
      the toughening phenomenon initiated by low level noise exposure we analyzed
      glutathione reductase, gamma-glutamyl cysteine synthetase, and catalase in stria
      vascularis and organ of Corti fractions from cochleae of chinchillas exposed to a
      sound conditioning paradigm. Chinchillas were either (A) kept in quiet cages
      (control), (B) exposed to conditioning noise of a 0.5 kHz octave band (90 dB for
      6 h/day for 10 days), (C) exposed to high level noise (105 dB for 4 h) or (D)
      exposed to conditioning noise (B) followed by exposure to the higher level noise
      (C). Each of the noise exposure conditions (B, C, D) induced changes in the
      levels of these three antioxidant enzymes. The enzyme-specific activity data for
      the four subject groups support the following two hypotheses. (1) Changes in
      glutathione reductase, gamma-glutamyl cysteine synthetase, and catalase play a
      role in attenuating hearing loss associated with sound conditioning followed by
      high level noise. (2) Hair cells in the organ of Corti are protected from noise
      induced damage by increasing stria vascularis levels of catalase, a hydrogen
      peroxide scavenging enzyme, and of enzymes involved in maintaining glutathione in
      the reduced state. The model formulated by these hypotheses suggests that agents
      that protect or augment the glutathione system in the cochlea may be protective
      against noise-induced hearing loss.

PMID- 9557977
TI  - Neural encoding of single-formant stimuli in the ventral cochlear nucleus of the
      chinchilla.
AB  - Responses of the principal unit types in the ventral cochlear nucleus of the
      chinchilla were studied with a single-formant stimulus set that covered
      fundamental frequency (f0) from 100 Hz to 200 Hz and formant center frequency
      (F1) from 256 to 782 Hz. Temporal coding for f0 and F1 was explored for 95
      stimulus combinations of f0 (n = 5) and F1 (n = 19) in primarylike, onset and
      chopper unit categories. Several analyses that explored temporal coding were
      employed including: autocorrelation, interspike interval analysis, and
      synchronization to each harmonic of f0. In general, the representation of f0 is
      better in onset and chopper units than in primarylike units. Nearly all units in
      the cochlear nucleus showed a gain in phase locking to the envelope (f0) of the
      single-formant stimulus relative to the auditory nerve. The fundamental is
      represented directly in neural discharges of units in the cochlear nucleus with
      an interval code (also Cariani and Delgutte, 1996; Rhode, 1995). The formant is
      represented in the temporal domain in primarylike units, though some chopper and
      onset units also possess the ability to code F1 through discharge synchrony.
      Onset-I units, which are associated with the octopus cells, exhibited the
      strongest phase locking to f0 of any unit types studied. The representation of f0
      and F1 in the temporal domain is weak or absent in some units. All-order
      interspike interval distributions computed for populations of units show
      preservation of temporal coding for both f0 and F1. Results are in agreement with
      earlier amplitude modulation studies that showed nearly all cochlear nucleus unit
      types phase lock to the signal envelope better than auditory nerve fibers over a
      considerable range of signal amplitudes.

PMID- 9557978
TI  - Frequency-shaped amplification changes the neural representation of speech with
      noise-induced hearing loss.
AB  - Temporal response patterns of single auditory nerve fibers were used to
      characterize the effects of a common hearing-aid processing scheme, frequency
      shaped amplification, on the encoding of the vowel /epsilon/ in cats with a
      permanent noise-induced hearing loss. These responses were contrasted with
      responses to unmodified stimuli in control and impaired cats. Noise-induced
      hearing loss leads to a degraded representation of the formant frequencies, in
      which strong phase locking to the formants is not observed in fibers with best
      frequencies (BFs) near the formants and there is a wide spread of formant phase
      locking to fibers with higher BFs (Miller et al., 1997a,b). Frequency shaping
      effectively limits the upward spread of locking to F1, which improves the
      representation of higher frequency components of the vowel. However, it also
      increases phase locking to harmonics in the trough between the formants, which
      decreases the contrast between F1 and the trough in the neural representation.
      Moreover, it does not prevent the spread to higher BFs of responses to the second
      and third formants. The results show a beneficial effect of frequency shaping,
      but also show that interactions between particular gain functions and particular
      spectral shapes can result in unwanted distortions of the neural representation
      of the signal.

PMID- 9557979
TI  - Effects of noise on inferior colliculus evoked potentials and cochlear anatomy in
      young and aged chinchillas.
AB  - Like many aging humans, the aging chinchilla tends to lose high-frequency
      sensitivity at a faster rate than low-frequency sensitivity. This feature,
      combined with its excellent low-frequency hearing, makes the chinchilla
      attractive as an animal model for studying the relationship between noise-induced
      hearing loss (NIHL) and age-related hearing loss (AHL). In the present study, we
      examined susceptibility to noise in 15 aged (10-15 years old) and 15 young
      chinchillas. Two levels of noise were used, with the aim of determining whether
      age-related differences exist in the magnitude and rate of recovery from
      temporary threshold shifts produced by a moderate-level (95 dB) noise exposure,
      or in susceptibility to permanent threshold shifts and cochlear damage caused by
      a high-level (106 dB) noise exposure. Thresholds and response amplitudes at 0.5,
      1, 2, 4, 8 and 16 kHz were determined from evoked potentials recorded from the
      inferior colliculus. Cochlear histology was performed on animals exposed to high
      level noise. The results suggest that older animals are equally vulnerable to
      moderate-level noise, but may be slightly more vulnerable to high-level noise.
      For moderate-level exposures, there appears to be a simple additive relationship
      (in dB) between AHL and NIHL. For high-level exposures, the relationship may be
      more complex.

PMID- 9557980
TI  - Development of auditory function in the tammar wallaby Macropus eugenii.
AB  - Auditory brainstem responses (ABRs) were evoked in developing wallabies by click
      and tone burst stimuli delivered by bone conduction and air conduction, at
      progressive stages of post-natal (pouch) life. ABRs were recorded through the
      onset of auditory responses (95-110 days), the opening of the external ear canal
      (125-130 days) and the maturation of ABR thresholds and latencies to values
      corresponding to those in adults ( > 180 days). ABRs were evoked in response to
      bone-conducted clicks some days prior to the age at which an acoustically evoked
      response was first observed (around 95 days of pouch life). ABRs could be evoked
      by bone-conducted and intense air-conducted stimuli prior to opening of the ear
      canal. A trend of decreasing threshold and latency with age was observed for both
      modes of stimulation. The morphology of the ABR became more complex, according to
      both increased age and increased stimulus intensity. The ABR waveforms indicated
      relatively greater mechanosensitivity to bone-conducted stimuli than to air
      conducted stimuli, prior to opening of the ear canal. Following opening of the
      ear canal, thresholds to air-conducted clicks and tones were substantially
      reduced and decreased further over the next 10-20 days, while thresholds to bone
      conducted clicks continued slowly to decrease. Thresholds to tone bursts in the
      centre frequency range (4-12 kHz) remained less than those for low (0.5-1.5 kHz)
      and higher (16 kHz) frequencies. Latencies of an identified peak in ABR waveforms
      characteristically decreased with age (at constant stimulus intensity) and with
      stimulus intensity (for a given age). ABR waveforms obtained at progressive ages,
      but judged to be at corresponding sensation levels, underwent maturational
      changes, independent of conductive aspects of the wallabies' hearing, for 2-3
      weeks after opening of the ear canal.

PMID- 9557981
TI  - A new method for the automated detection of spontaneous otoacoustic emissions
      embedded in noisy data.
AB  - There is, as yet, no universally agreed upon method for the detection of
      spontaneous otoacoustic emissions (SOAEs). In this paper, we augment extant
      techniques by presenting a new automated approach. The new procedure reliably
      labels the spectral peaks as SOAEs, rejects noisy data such as that due to body
      movements or breathing, provides a subject-specific measure of the probability
      that a particular peak is erroneously identified as a SOAE, and can be
      accomplished on-line. Comparison of results with this new approach and with
      methods undertaken previously in this laboratory and elsewhere are made. The
      estimated prevalence of SOAEs for the new method is as large as that for any
      method previously proposed.

PMID- 9557982
TI  - Contralateral frequency-modulated tones suppress transient-evoked otoacoustic
      emissions in humans.
AB  - In order to test the sensitivity of the human medial olivocochlear bundle (MOCB)
      to stimulus frequency fluctuations, changes in transient-evoked otoacoustic
      emission (TEOAE) amplitude induced by frequency modulated (FM) tones were
      measured in 18 normal-hearing subjects. The results revealed that TEOAE amplitude
      was reduced by contralateral FM tones at 40 dB above pure-tone threshold, with
      significant influences of both modulation rate (MR) and modulation depth (MD).
      This finding is discussed in the light of other recent results indicating
      amplitude fluctuation and frequency bandwidth effects in MOCB activation in
      humans.

PMID- 9557983
TI  - Induction of endolymphatic hydrops in the guinea pig by perisaccular deposition
      of sepharose beads carrying and not carrying immune complexes.
AB  - We tried to induce endolymphatic hydrops in guinea pig cochleas by unilateral,
      perisaccular deposition of sepharose beads carrying immune complexes. Controls
      consisted of the deposition of sepharose beads without immune complexes and the
      contralateral, untreated ear. The effects of the treatment were studied by light
      microscopy and electrophysiological recordings of the gross cochlear potentials
      1, 2, and 6 weeks after treatment. Each condition included six animals. Analysis
      of variance of the morphometric data concerning the ears treated with deposition
      of the beads showed a statistically significant difference (P = 0.04) between the
      degree of hydrops found for the beads with immune complexes and for those
      without. The difference between the treated ears and the contralateral untreated
      ears was significant (P = 0.01) for the beads with immune complexes and not
      significant (P = 0.8) for those without immune complexes while there was no
      significant effect of post-treatment time interval. Analysis of variance of the
      electrophysiological data, collected in response to tone bursts at the apex of
      the cochlea, showed no significant differences between the results for the beads
      with and without immune complexes. Therefore these results were pooled. One week
      after treatment the pooled results for the compound action potential showed a
      small decrease in amplitude, just significant at 2 kHz, but not at 4 and 8 kHz.
      This decrease disappeared completely after 6 weeks. The pooled results for the
      negative summating potential (SP) showed a significant increase in magnitude at
      all frequencies decreasing with post-treatment interval. The cochlear
      microphonics did not demonstrate any change in amplitude after treatment. The
      results indicate that deposition of sepharose beads with immune complexes induces
      endolymphatic hydrops. Also, deposition of the sepharose beads itself may have
      induced hydrops together with enhancement of the SP. SP enhancement may be
      related to the development of endolymphatic hydrops rather than to the presence
      of hydrops as such. This may be based on pressure build-up while hydrops
      develops.

PMID- 9557985
TI  - Salicylate and quinine selectively increase spontaneous firing rates in secondary
      auditory cortex.
AB  - This study presents firing rates for simultaneously recorded spontaneous and
      stimulus driven multi-unit activity in primary auditory cortex (AI), anterior
      auditory field (AAF) and secondary auditory cortex (AII) in cats before and after
      application of salicylate or quinine. From 21 cats, in three cortical areas
      simultaneously, a total of 1533 multi-unit files were obtained. The data suggest
      (1) that both salicylate and quinine significantly increase spontaneous firing
      rates in AII, whereas in AI and AAF both quinine and salicylate reduced the
      spontaneous rate; (2) the effect of both drugs was to increase spontaneous rates
      for recording sites with high characteristic frequency (CF) and a tendency to
      decrease them for low CF sites; (3) the mean stimulus driven firing rates were
      not affected by either drug except for a decrease produced by quinine in AI; (4)
      changes in driven firing rate were positively correlated with changes in
      spontaneous firing rates. This suggests that tinnitus inducing agents selectively
      increase spontaneous firing rates in the extralemniscal pathway.

PMID- 9557984
TI  - Expression of mRNA encoding vasopressin V1a, vasopressin V2, and ANP-B receptors
      in the rat cochlea.
AB  - The expression of mRNAs encoding vasopressin V1a, V2, and ANP-B receptors in the
      rat cochlea was examined by PCR and in situ hybridization. After reverse
      transcription of rat cochlear RNA, cDNA was amplified by PCR using pairs of
      primers specific to these receptors. After subcloning of the PCR products, clones
      with sequences identical to those cloned previously from the rat liver (V1a
      receptor), kidney (V2 receptor) and brain (ANP-B receptor) were obtained. The
      localization of expression of those receptors in the developing and adult rat
      cochlea was examined by in situ hybridization using 35S-labeled cRNA probes. The
      V1a and V2 receptors were expressed throughout the whole of the neonatal rat
      cochlea, while no expression was detected in the adult cochlea. The ANP-B
      receptor was expressed throughout the whole of the neonatal cochlea. In the adult
      cochlea, expression was observed in the spiral ganglion and the spiral ligament.
      These results suggest that vasopressin may play a role in the development of the
      cochlea, and that natriuretic peptide may play a role in the function of the
      spiral ganglion and the spiral ligament.

PMID- 9557986
TI  - Distribution of Eph-related molecules in the developing and mature cochlea.
AB  - Receptors and ligands of the Eph family have recently been shown to influence the
      development of a variety of tissues. In the present study, the temporal and
      spatial distribution of Eph receptors and ligands were investigated in the
      embryonic and postnatal cochlea using Northern blot and immunohistochemical
      analysis. The results of Northern blot experiments revealed that a large number
      of Eph family members were present in embryonic cochlear and vestibular ganglia.
      Immunohistochemical studies revealed that ligands and receptors of the GPI
      subclass were distributed in complementary patterns within the differentiating
      spiral limbus, inner sulcus and outer sulcus. The distribution of these molecules
      became more restricted beginning in the first postnatal week. In contrast,
      members of the transmembrane subclass of Eph ligands were largely associated with
      cochlear neurons and their target hair cells. Expression of these ligands
      appeared to increase during the second postnatal week, corresponding to the
      period of peripheral nerve fiber reorganization in the cochlea. Together, these
      studies suggest that multiple Eph family members play unique roles in formation
      of the cochlea.

PMID- 9557988
TI  - The pain of interstitial cystitis.

PMID- 9557987
TI  - Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr
      mouse spleen cells.
AB  - Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr
      mouse spleen cells The MRL/lpr mouse, which has a mutation in the Fas gene
      encoding a cell-surface receptor for apoptosis, shows an accumulation of abnormal
      immunocompetent cells and SLE-like disease. It has recently been reported that
      this mouse also manifests sensorineural hearing loss (SHL) with cochlear
      pathology at 20 weeks of age. We examined the effects of injecting MRL/lpr spleen
      cells on the development of SHL in severe combined immunodeficient (SCID) mice,
      which originally develop neither SHL nor cochlear pathology. Immune-mediated SHL
      and cochlear pathology were, indeed, transferred to the SCID mice by the
      injection of spleen cells from the MRL/lpr mice. These findings suggest that cell
      mediated immunity is involved in the development of SHL and cochlear pathology.

PMID- 9557989
TI  - Intraoperative transvesical cystoscopy for urogynecologic procedures.
AB  - Intraoperative cystoscopy is a useful adjunct to surgical procedures that may
      compromise the integrity of the lower urinary tract. Ureteral injury and the
      placement of intravesical sutures are risks, especially at teaching facilities,
      during operations such as retropubic urethropexy, paravaginal repair, or even
      simple hysterectomy. The conventional use of transurethral cystoscopy during open
      surgical cases may require repositioning of the patient if not previously placed
      in Allen stirrups. Alternative practices of bladder examination include placement
      of a standard cystoscope via an intentional cystotomy through the dome of the
      bladder. The authors have implemented the direct insertion of a 2 mm
      microlaparoscope through the bladder dome to verify an intact lower urinary
      system and found this method to be both efficacious and safe. Visualization is
      not compromised by the slightly smaller visual field compared to the standard 0
      degrees or 30 degrees cystoscope. The perspective of the bladder neck region may
      be more easily oriented from the superior viewing angle. The authors prefer
      transvesical cystoscopy with the microlaparoscope for its ease of use, compared
      to their experience of performing a small cystotomy or routine transurethral
      cystoscopy.

PMID- 9557990
TI  - New ambulatory surgical methods using an anatomical classification of urinary
      dysfunction improve stress, urge and abnormal emptying.
AB  - The aim of the study was to introduce an anatomical classification for the
      management of urinary dysfunction based on the Integral Theory, a new connective
      tissue theory for female incontinence. Eighty-five unselected patients, aged 27
      83 years, 12 with pure stress symptoms and 73 with mixed incontinence symptoms,
      were classified as having laxity in the anterior, middle or posterior zones of
      the vagina, using specific symptoms, signs and urodynamic parameters summarized
      in a pictorial algorithm. Special ambulatory surgical techniques, which included
      the creation of neoligaments, repaired specific connective tissue defects in the
      anterior (intravaginal slingplasty (IVS), n = 85), middle (cystocele repair, n =
      6), or posterior zones (uterine prolapse repair, n = 31, or infracoccygeal
      sacropexy, n = 33). Almost all patients were discharged within 24 hours of
      surgery, without postoperative catheterization, returning to fairly normal
      activities within 7-14 days. At (mean) 21-month follow-up cure rates were: stress
      incontinence 88% (n = 85), frequency 85% (n = 42), nocturia 80% (n = 30), urge
      incontinence 86% (n = 74), emptying symptoms 50% (n = 65). Mean objective urine
      loss (cough stress test) was reduced from 8.9 g preoperatively to 0.3 g
      postoperatively, and mean residual urine >50 ml from 110 ml to 63 ml, P = <0.02.
      Pre- and postoperative urodynamics indicated that detrusor instability was not
      associated with surgical failure. Two new directions, based on the Integral
      Theory, are presented for the management of female urinary dysfunction, an
      anatomical classification which delineates three zones of vaginal damage, and a
      series of ambulatory surgical operations which repair these defects. The
      operations are fairly simple, safe, effective and easily learnt by any practising
      gynecologist.

PMID- 9557991
TI  - Transabdominal repair of cystocele by wedge colpectomy during combined abdominal
      vaginal surgery.
AB  - The aim of the study was to evaluate the effectiveness of transabdominal wedge
      colpectomy as surgical treatment for cystocele. One hundred and sixty-three women
      with either first or second-degree cystocele (Beecham classification), rectocele
      and concomitant stress urinary incontinence or benign pelvic masses were
      submitted for a combined operation. Transabdominal repair of the cystocele was
      performed by wedge colpectomy employing two different absorbable sutures, Vicryl
      and PDS. The choice of suture was not random but depended on the period at which
      surgery was performed. Data obtained were analyzed with Student's t-test and
      Fisher's exact test. The cystocele cure rate was 90.2% (110 out of 122) at 3-year
      follow-up and was significantly associated with the preoperative degree, being
      95.5% and 76.5% in first and in second degree, respectively (P = 0.003). At 1
      year follow-up the cure rate was significantly associated with the type of the
      suture employed (P = 0.01). At 2-year follow-up rectocele cure rate was 97.2% and
      vaginal vault prolapse appeared in 3.5% of cases. Stress urinary incontinence
      relapsed in 10% of patients after Burch colposuspension. After the operation
      94.1% of the women declared normal coitus. In the present series wedge colpectomy
      was found to be effective in repairing first-degree cystocele, whereas a high
      incidence of relapse was observed when second-degree cystocele was present
      preoperatively. The suture material employed influenced the cure rate.

PMID- 9557992
TI  - Augmentation of urethral pressure profile by voluntary pelvic floor contraction.
AB  - The aim of the investigation was to study the repeatability of urethral pressure
      profile (UPP) and to quantify the influence of voluntary pelvic floor contraction
      on the UPP. Seventy-two patients underwent one UPP at rest and one UPP during a
      pelvic floor contraction. The functional urethral length (FUL) and the maximum
      urethral closure pressure (MUCP) were recorded. To establish repeatability the
      UPP was repeated twice in 18 patients in rest, and in 15 patients during a
      contraction. We used the repeatability coefficient instead of the correlation
      coefficient. Forty-eight patients, had no major anatomical abnormalities (group
      A); 24 had grade 2 or more prolapse (group B). In both groups we found a
      shortening of the FUL and an increase in MUCP during a contraction. The UPP was
      reproducible, both at rest and during a contraction. In conclusion, we found a
      significant and constant increase in MUCP and a shortening of the FUL during a
      contraction. Unlike other studies we found the UPP to have good reproducibility.
      However, we used the repeatability coefficient instead of the correlation
      coefficient.

PMID- 9557993
TI  - Cystocele--a radical cure by suturing lateral sulci of the vagina to the white
      line of pelvic fascia. 1909.

PMID- 9557994
TI  - Pentosanpolysulphate for interstitial cystitis.
AB  - Interstitial Cystitis (IC) is a chronic disease of unknown etiology which
      primarily affects women aged 40-60 years. Many plausible theories for the
      development of IC have been postulated, and one current theory is that these
      patients have a quantitative and qualitative defect in the glycosaminoglycan
      (GAG) layer of the urothelium. Such a defect may allow toxic substances in the
      urine to gain access to the lamina propria and initiate a chronic inflammatory
      process. Pentosanpolysulphate (PPS) is a sulphated proteoglycan similar in
      structure to heparin sulphate, which is quantitatively the major GAG on cell
      surfaces. Exogenously administered PPS has been shown in several studies to
      decrease bladder pain and urinary frequency and to increase the voided volume.
      Further studies are required to evaluate the role of PPS in the management of IC
      patients, with particular emphasis on dosage, route of administration and
      combination with other compounds.

PMID- 9557995
TI  - Pelvic floor muscle exercises in genuine urinary stress incontinence.
AB  - Pelvic floor muscle exercises, in the treatment of genuine stress incontinence,
      have been used successfully since 1948. One may expect a significant improvement
      (warranting no further therapy), or cure rate of about 50%. These exercises have
      a long-lasting effect. Poorly motivated women should be discouraged to follow
      exercise sessions. An active co-operation between urogynecologist,
      physiotherapist and the patient is important in order to avoid undertreated and
      dissatisfied women. The option to be operated upon must be easily available.

PMID- 9557996
TI  - Introl bladder neck support prosthesis: international clinical experience.
AB  - The Introl bladder neck support prosthesis is a ring-shaped silastic device with
      two prongs located at one side such that when placed within the vaginal canal the
      bladder neck is suspended in a fashion similar to a surgical urethropexy. Since
      its initial description in 1988 the device has undergone clinical trials in the
      US and Japan, documenting its effectiveness in the treatment of stress and mixed
      incontinence in women. Introl is available for clinical use in the United States
      and has been well accepted by practicing clinicians. In Japan, exposure has
      occurred through clinical trials, which resulted in a high efficacy rate, i.e.
      81% of the patients had either maximum benefit or benefit in the global
      usefulness rating, and 26% experienced minor adverse effects. This paper will
      summarize Introl clinical study findings and describe various clinical
      observations made during increased clinical usage.

PMID- 9557997
TI  - Clinical usefulness of urinary control urethral insert devices.
AB  - Urinary control urethral insert devices have been introduced as a non-surgical
      remedy to treat female urinary incontinence. Several early clinical trials have
      demonstrated the degrees of safety and efficacy, and have defined the morbidity
      and complications of these urethral inserts. This is a descriptive review of
      urethral insert devices in clinical use or currently undergoing clinical
      investigation.

PMID- 9557999
TI  - Re: change in urethral pressure during voluntary pelvic floor muscle contraction
      and vaginal stimulation. Bo K, Talseth T. Int Urogynecol J 1997;8:3-7.

PMID- 9557998
TI  - Clinical value of vaginal cones for the management of female stress incontinence.
AB  - In women with mild stress incontinence (mean urine loss of 3.7 g/h), pelvic floor
      training using vaginal cones resulted in a subjective success rate of 70%
      (19/27), that is complete cure or reduction by >50% of the original severity.
      However, in women with severe stress incontinence (mean urine loss of 20.7 g/h)
      cone therapy was successful in only 14% (7/50). The predictive value of six
      parameters (age, parity, urine loss by pad test, frequency of incontinence,
      contractile strength of the vagina, and perceived problems) was analyzed and two
      showed significant prognostic values: a smaller amount of urine loss and less
      frequent incontinence. It is concluded that vaginal cone therapy is one physical
      treatment option for stress incontinence but is of no clinical effect for those
      with severe incontinence.

PMID- 9558000
TI  - Tumor and dendritic cells as cellular vaccines: confrontation and perspectives--a
      symposium in writing.

PMID- 9558001
TI  - Tumor antigen presentation: changing the rules.
AB  - Cell-based tumor vaccines have been developed on the basis of the hypothesis that
      tumor cells can be genetically modified to present antigen to T lymphocytes
      directly. Contrary to expectations, cross-priming is the predominant pathway for
      activation of tumor-specific CD8+ T cells, while direct presentation of antigen
      dominates activation of tumor-specific CD4+ T cells. These results pose
      interesting paradoxes for the generation of immune responses, and have definite
      implications for the development of anti-cancer vaccines.

PMID- 9558002
TI  - Tumor immunotherapy: cytokines and antigen presentation.
AB  - Increasing the ability of tumor-reactive T cells to mediate tumor regression in
      vivo has been a major goal of tumor immunologists. Progress toward this goal has
      been aided by the identification of tumor-associated antigens on both
      experimental mouse tumors and human tumors. However, the self-like nature and low
      immunogenicity of these antigens has made it clear that other measures to enhance
      the effectiveness of the T cells reactive to these antigens are essential if
      immunotherapy is to be clinically effective. An increased understanding of
      antigen processing and presentation is an important step in this process, as is
      the use of cytokines to increase immune responsiveness. Despite recent advances,
      there is still much to be learned before the specificity of the immune system is
      safely harnessed to halt malignant cell growth effectively.

PMID- 9558003
TI  - Immunotherapy of cancer with dendritic-cell-based vaccines.
AB  - Animal studies have shown that vaccination with genetically modified tumor cells
      or with dendritic cells (DC) pulsed with tumor antigens are potent strategies to
      elicit protective immunity in tumor-bearing animals, more potent than
      "conventional" strategies that have been tested in clinical settings with limited
      success. While both vaccination strategies are forms of cell therapy requiring
      complex and costly ex vivo manipulations of the patient's cells, current
      protocols using dendritic cells are considerably simpler and would be more widely
      available. Vaccination with defined tumor antigens presented by DC has obvious
      appeal. However, in view of the expected emergence of antigen-loss variants as
      well as natural immunovariation, effective vaccine formulations must contain
      mixtures of commonly, if not universally, expressed tumor antigens. When, or even
      if, such common tumor antigens will be identified cannot be, predicted, however.
      Thus, for the foreseeable future, vaccination with total-tumor-derived material
      as source of tumor antigens may be preferable to using defined tumor antigens.
      Vaccination with undefined tumor-derived antigens will be limited, however, by
      the availability of sufficient tumor tissue for antigen preparation. Because the
      mRNA content of single cells can be amplified, tumor mRNA, or corresponding cDNA
      libraries, offer an unlimited source of tumor antigens. DC transfected with tumor
      RNA were shown to engender potent antitumor immunity in animal studies. Thus,
      immunotherapy using autologous DC loaded with unfractionated tumor-derived
      antigens in the form of RNA emerges as a potentially powerful and broadly useful
      vaccination strategy for cancer patients.

PMID- 9558004
TI  - Keeping the immune system alerted against cancer.

PMID- 9558007
TI  - A case report of immunotherapy on a patient with advanced gastric cancer by
      adoptive transfer of OK-432-reactive HLA-matched allogeneic lymphocytes.
AB  - Adoptive immunotherapy (AIT) for non-hematological malignancies, using HLA
      matched donor lymphocytes, has been rarely reported. For a 35-year-old male
      patient with peritoneal disseminated advanced gastric cancer, we performed AIT
      using lymphocytes from his HLA-matched 37-year-old brother and a streptococcal
      preparation, OK-432, as an antigen. After the donor had been immunized by
      intradermal administration of OK-432, OK-432-reactive lymphocytes were induced in
      vitro and transferred to the patient intravenously with OK-432. Low-dose systemic
      immunochemotherapy, using interleukin-2, 5-fluorouracil and cyclophosphamide, was
      concurrently administered with AIT. As a result, the Schnitzler metastasis in the
      patient reduced in size without any significant graft-versus-host-related
      complications. One of the effector mechanisms of therapeutic benefit was
      suggested to be cytokine release from the transferred OK-432-reactive
      lymphocytes. Our findings suggest the safety and efficacy of AIT using
      lymphocytes from an HLA-matched sibling and OK-432 as an antigen. Further studies
      to investigate the use of tumor-associated antigen and an HLA-matched sibling's
      lymphocytes for AIT of advanced cancer are warranted.

PMID- 9558006
TI  - Effects of paclitaxel on cytokine synthesis by unprimed human monocytes, T
      lymphocytes, and breast cancer cells.
AB  - Paclitaxel or Taxol has attracted a great deal of attention in recent years
      because of its immense success as a chemotherapeutic agent for numerous types of
      cancer. It is known that paclitaxel stabilizes microtubules, and this
      characteristic is the presumed primary mechanism for its antitumor activity.
      Recently, however, paclitaxel's ability to regulate gene expression, particularly
      in the murine system, has been reported by several groups. Here, we present
      research examining paclitaxel's ability to alter expression of the interleukin
      1beta (IL-1beta) and IL-8 cytokines in primary human monocytes, T lymphocytes,
      and four human breast cancer cell lines: MCF-7, ZR-75-1, MDA-MB-468, and MDA-MB
      231. This report shows for the first time that treatment with 5-50 microM
      paclitaxel increases steady-state levels of IL-1beta mRNA in unprimed human
      monocytes, MCF-7, and ZR-75-1 cells. Monocytes from eight donors in 16
      experiments showed increased IL-1beta secretion upon treatment; however, the
      increase in IL-1beta production by monocytes was predicated on culturing in the
      absence of fetal bovine serum or in the presence of autologous human serum. In
      contrast to the IL-1beta results, paclitaxel did not have significant effects on
      IL-8 expression by monocytes, T lymphocytes, or the breast cancer cells. These
      data show a specific effect of paclitaxel on cytokine synthesis by both immune
      cells and cancer cells.

PMID- 9558005
TI  - Contribution of the T cell receptor BJ gene to recognition of the P91A tumor
      antigen in DBA/2 mice.
AB  - To understand specific immune responses against a tumor, it is important to
      characterize T cells that recognize the tumor antigen. The mouse P91A antigen is
      one of the well-defined tumor antigens that is expressed on the P911 cell line,
      and T cells responding to the antigen in DBA/2 mice were reported to be
      restricted to BV8S2/S3 families in their T cell receptor (TCR) BV gene usage. We
      have further characterized the P91A-responding T cells in DBA/2 mice, focusing on
      TCR BJ gene usage and using the polymerase chain reaction/enzyme-linked
      immunosorbent assay and DNA sequencing studies of their third complementarity
      determining (CDR3) regions. As a result, T cells with cytotoxic activity to the
      P91A antigen, induced from murine spleen cells both in vivo and in vitro, showed
      predominant use of the BJ2S1 gene segment in both BV8S2 and BV8S3 T cells
      compared to unmanipulated murine spleen cells. Sequencing studies of the CDR3
      regions in the BV8S3 T cells revealed clonal expansion of T cells with the BV8S3
      BJ2S1 combination in two of three DBA/2 mice tested. In the remaining mouse,
      clonal expansion was not detected despite predominant use of the BJ2S1 segment by
      these T cells. These data suggest that P91A-recognizing T cells would
      predominantly use the BV8S2/S3-BJ2S1 combination. Analysis of T cells with these
      TCR BV-BJ gene combinations may contribute to the evaluation, monitoring and
      development of a T-cell-mediated immunotherapeutic strategy.

PMID- 9558009
TI  - Relationship between muscle abnormalities and symptom duration in lumbosacral
      radiculopathies.
AB  - A long held notion in the electrodiagnostic literature is that paraspinal muscles
      tend to show electromyographic abnormalities early on in a lumbosacral
      radiculopathy and that more distal muscles become abnormal later in the disease
      process. The purpose of this study was to determine whether paraspinal muscles
      and other major proximal and distal muscle abnormalities are related to
      lumbosacral radiculopathy symptom duration. A multivariate logit analysis of 139
      patients (retrospectively identified) with electrodiagnostically confirmed
      lumbosacral radiculopathies was used to test these hypotheses. Maximum likelihood
      estimates showed no evidence of correlation between abnormal paraspinal muscles
      and symptom duration. Symptom duration was also insignificant for the remaining
      five lower limb muscles analyzed. We conclude that the probability of having
      electromyographic abnormalities is not related to symptom duration. A prospective
      study is needed to confirm these findings. Nonetheless, clinicians should use
      caution when interpreting electrodiagnostic findings based on symptom duration.

PMID- 9558008
TI  - Comparison of visual inspection and statistical analysis of single-subject data
      in rehabilitation research.
AB  - Single-subject designs are being advocated to conduct outcome research in
      rehabilitation environments. The methods provide an alternative to traditional
      designs based on statistical comparisons across groups. Data analysis in single
      subject research does not rely on statistical hypothesis testing of responses
      collected from a sample of subjects. Instead, visual inspection of patient
      responses graphed over time is the usual method of data analysis in single
      subject research. This study examined the agreement between visual analysis and
      statistical tests of single-subject data for 42 hypothetical single-subject
      graphs. Specially constructed graphs allowed the systematic manipulation of
      different treatment effect sizes across a commonly used single-subject design.
      Thirty-two rehabilitation and health care providers rated each of the 42 graphs
      to determine whether a clinically significant treatment effect existed across the
      phases of the designs. Data analysis focused on two questions: (1) How much
      agreement was there between visual judgments and the results of statistical
      tests? and (2) What level of treatment effect was required to produce a finding
      of visual versus statistical significance? The agreement between visual analysis
      and statistical significance was high (86%). The sensitivity of visual inferences
      compared with statistical test results was 0.84, specificity was 0.88, and
      positive predictive value was 0.91. Both visual and statistical procedures were
      sensitive to medium and large treatment effects in the 42 single-subject graphs
      examined in this study.

PMID- 9558010
TI  - Impaired hypothalamus-pituitary-adrenal axis in men with spinal cord injuries.
AB  - Twenty-five men with spinal cord injuries were studied for evaluation of the
      hypothalamus-pituitary-adrenal axis, using corticotropin-releasing hormone and
      insulin-induced hypoglycemia. Twenty-five age-matched healthy male volunteers
      served as controls. Three spinal cord-injured subjects had hyperprolactinemia,
      three had elevated basal follicle-stimulating hormone levels, one had an elevated
      basal luteinizing hormone level, and four had hypotestosteronemia. The mean
      plasma adrenocorticotropin response to corticotropin-releasing hormone of spinal
      cord-injured subjects was smaller than that of the healthy controls but did not
      reach a statistical significance. The cortisol response to corticotropin
      releasing hormone of the spinal cord-injured subjects was significantly lower
      than that of healthy controls. However, the difference disappeared if a
      correction was made for baseline values. Six spinal cord-injured subjects did not
      have a cortisol response to insulin-induced hypoglycemia, and they had either a
      minimal or no adrenocorticotropin response. Another 11 spinal cord-injured
      subjects had a maximal cortisol response to insulin-induced hypoglycemia below
      the lowest limit of normal, i.e., 0.5 micromol/l. Among these spinal cord-injured
      subjects, three had a less than 50% increase of plasma adrenocorticotropin after
      insulin-induced hypoglycemia. These findings are consistent with the notion that
      spinal cord-injured subjects have an altered central neurotransmitter tone and
      substantiate the hypothesis that an afferent neural pathway exists between the
      adrenal and hypothalamus and may modulate stress-induced secretion of
      adrenocorticotropin. Long-term abnormal adrenocorticotropin secretion may cause
      mild adrenocortical atrophy and, thereby, a reduced cortisol response.

PMID- 9558011
TI  - Common causes of knee effusions in spinal cord injury: a random study.
AB  - Patients with spinal cord injury are predisposed to knee effusions owing to
      osteoporosis, heterotopic ossification, trauma, and benign hydrarthrosis. This
      retrospective review discusses 11 patients with spinal cord injury and knee
      effusions seen during two years. One objective is to correlate the initial
      diagnosis based on clinical findings with the final diagnosis based on synovial
      fluid analysis and radiographic studies. Another is to describe the variety and
      complexity of clinical situations that involve knee effusions in spinal cord
      injury. The initial diagnosis was different from the final diagnosis in all of
      our cases. The final diagnoses were trauma (6 cases), pseudogout (2 cases),
      spasticity, fracture of the tibial plateau, septic joint, and tears of the
      anterior cruciate and lateral collateral ligaments. Knee effusions in this unique
      population must be carefully investigated to avoid erroneous diagnoses based on
      the initial clinical presentation, which can be complicated by multiple medical
      problems.

PMID- 9558012
TI  - Evident transsynaptic degeneration of motor neurons after spinal cord injury: a
      study of neuromuscular jitter by axonal microstimulation.
AB  - Neuronal degradation accompanied with axonal degeneration has been known to occur
      in spinal motor neurons after an upper level of spinal cord lesion. In the
      present study, the functional integrity of neuromuscular transmission was
      assessed by utilizing a sensitive electrodiagnostic method comprising of
      stimulated single-fiber electromyography (SFEMG), along with axonal
      microstimulation, in paralytic muscles of patients with spinal cord injury (SCI).
      Neuromuscular jitter was measured in anterior tibial muscles for 30 patients with
      SCI and also for 12 normal controls. Mean jitter of 37.4 +/- 14.7 (mean +/- SD)
      micros, as obtained in SCI patients, was found to be significantly greater than
      the results of 20.1 +/- 8.4 micros in normal controls (P < 0.01). Jitter
      measurement was not significantly different in varied functional scales of SCI. A
      positive correlation was noted between the increased jitter and the disease
      duration from the onset of cord lesion till the time of stimulated SFEMG test (r
      = 0.68; P < 0.01). The present abnormal finding of neuromuscular jitter provides
      an electrophysiologic evidence for axonal degeneration and suggests that
      transsynaptic degeneration of motor neuron may occur below the level of cord
      lesion in SCI patients. Furthermore, the neuronal degradation in SCI was
      positively correlated with the course duration of the disease.

PMID- 9558013
TI  - Effect of activities of daily living on fiber type atrophy of the vastus
      lateralis muscle in patients with joint disorders.
AB  - The histopathologic study was performed to elucidate whether the fiber type
      atrophy of the vastus lateralis muscle in patients with hip or knee joint
      disorders is related to the activities of daily living (ADL) or habitual physical
      activity. Subjects were 16 female patients, 52.4 +/- 16.0 yr of age (mean +/-
      standard deviation), who underwent a vastus lateralis muscle biopsy at the time
      of total hip or knee replacement. At the time of referral to the rehabilitation
      center, the Functional Independence Measure (FIM) motor score and habitual
      physical activity at home were evaluated, and the diameter and atrophy factor for
      each muscle fiber type were measured on the histopathologic preparations of the
      biopsied muscles. The data were analyzed using ttest, one-way analysis of
      variance (ANOVA), Kruskal-Wallis one-way ANOVA, Spearman's correlation
      coefficient, and partial correlation coefficient. The patients showed muscle
      fiber atrophy and small angular fibers, and the atrophy factor was significantly
      increased in type 1, 2A, and 2B fibers, in that order (one-way ANOVA, P < 0.05).
      The patterns of the fiber type atrophy, consisting of normal, type 2B atrophy,
      type 2AB atrophy, and type 1 and 2AB atrophy, had a significant relationship with
      the fiber type atrophy (Spearman's correlation coefficient; rho = 0.834, P <
      0.001). The FIM motor score showed a significant correlation with the atrophy
      factor (r = -0.584, P < 0.05), and significant differences were recognized among
      the four patterns of the fiber type atrophy (Kruskal-Wallis one-way ANOVA, P <
      0.05). In conclusion, the muscle atrophy and patterns of the fiber type atrophy
      of the vastus lateralis muscle in patients with joint disorders may be related to
      changes in the FIM motor score.

PMID- 9558014
TI  - Varied morphology of spontaneous single muscle fiber discharges.
AB  - Fibrillation potentials and positive sharp waves have rather stereotypical
      morphologies generally conforming to a triphasic initially positive and biphasic
      initially positive waveform, respectively. Careful attention during the needle
      electromyographic examination of muscle tissue with unstable resting membrane
      potentials, however, frequently reveals spontaneous potentials with appearances
      conforming to not only those described above but also waveforms with morphologies
      that can best be characterized as a blend of both a fibrillation potential and
      positive sharp wave. These "hybrid" or composite waveforms are hypothesized to
      arise from an electrical summation of two single muscle fibers repetitively
      discharging in a time-locked manner. Five individuals with lower motor neuron
      disorders displaying spontaneous discharges at rest during the needle
      electromyographic were examined. The spontaneous discharges were categorized
      according to their morphology. Stereotypical positive and negative onset
      fibrillation potentials and positive sharp waves from these patients were
      digitized. Computer simulations summating the digitized waveforms were successful
      in reproducing all of the observed "hybrid" waveforms documented in the patients.
      The supposition of two single muscle fibers discharging within a temporal domain
      conducive to electrical summation is an extension of the concept that electrical
      summation of muscle fibers comprising a motor unit summate to generate an
      electrical representation of that motor unit.

PMID- 9558015
TI  - Subjective recovery time after exhausting muscular activity in postpolio and
      control subjects.
AB  - The purpose of this study was to determine whether the time to subjectively fully
      recover after the performance of exhausting muscular exercise was greater in
      unstable postpolio as compared with stable postpolio or control subjects. Twenty
      five unstable (those complaining of declining muscle strength) postpolio, 16
      stable (those denying declining muscle strength) postpolio, and 25 control
      subjects performed an isometric contraction of the knee extensor (quadriceps
      femoris) musculature at 40% of maximal torque until they were no longer able to
      do so. Five-second maximal effort contractions were made every 30 s through 2 min
      after the time of failure was reached and then at 1-min intervals through 10 min
      after failure was reached. Subjects reported the duration of time required to
      subjectively fully recover from this activity. Choices of "less than 1 day," "1
      day," "2 days," etc., up to "greater than 2 wk" were given to the subjects for
      their response. Analysis was by nonparametric ANOVA and appropriate post hoc
      comparison procedures. Unstable postpolio subjects reported a greater recovery
      time than either the stable postpolio or control subjects (mean +/- SD of 2.6 +/-
      3.0 days, 0.6 +/- 1.0 days, and 0.7 +/- 1.1 days, respectively, P < 0.05). Thus,
      the reported recovery time from exhausting isometric muscular exercise was found
      to be greater in unstable postpolio subjects than stable postpolio or control
      subjects. The cause for this finding is unknown and requires further
      investigation.

PMID- 9558017
TI  - Transient osteoporosis of the hip during pregnancy: a case report.
AB  - Transient osteoporosis associated with pregnancy is a rare, self-limiting
      skeletal disorder, the origin of which remains unclear. We report the case of a
      36-year-old Japanese woman who developed pain in the left hip, groin, and knee in
      the seventh month of pregnancy. The pain gradually worsened and prevented weight
      bearing. The hip and knee pain progressed to bilateral involvement and persisted
      after an emergent cesarean section at 35 weeks. Radiographs after delivery
      revealed gross osteopenia of both the femoral heads, left distal femur, and
      proximal tibia, consistent with transient osteoporosis associated with pregnancy.
      The patient remained mostly wheelchair-dependent because of severe hip and knee
      pain. Several weeks later, the patient was started on alendronate, a
      biphosphonate, which provided dramatic relief of hip and knee pain. The patient's
      ambulatory function subsequently improved dramatically as a result of pain relief
      and assistance with gait training. This case is unique for several reasons.
      First, it is rare for transient osteoporosis associated with pregnancy to involve
      both hip joints, and it rarely involves the knee. Second, this is the first
      reported case of pain management of transient osteoporosis associated with
      pregnancy being successfully treated with an antiresorptive agent. Finally, the
      use of alendronate in transient osteoporosis associated with pregnancy may help
      shorten disability by providing pain relief and decreasing the fracture risk
      associated with this disease.

PMID- 9558016
TI  - Comparison of three protocols for breathing exercises during immersion in 38
      degrees C water for chronic obstructive pulmonary disease.
AB  - Respiratory function test, arterial blood gas analysis, and ejection fraction
      were used to compare three protocols of breathing exercises during immersion in
      38 degrees C water. Therapy was given for 2 mo to patients with stable chronic
      obstructive pulmonary disease. Protocol A consisted of a total exercise period of
      20 min/wk (10 min/day, 2 days/wk) and was performed by 7 patients (5 cases of
      asthma and 2 cases of emphysema). Protocol B consisted of a total exercise period
      of 120 min/wk (20 min x 2 per day at 10:00 am and 3:00 pm, 3 days/wk) and was
      performed by 9 patients (6 asthmas and 3 emphysemas). Protocol C consisted of a
      total exercise period of 120 min/wk (20 min/day, 6 days/wk) and was performed by
      8 patients (4 asthmas and 4 emphysemas). The ratio of forced expired volume in
      one second to forced vital capacity (FEV1.0%) was significantly increased in
      protocols B and C (P < 0.01). The ratio of forced vital capacity to the predicted
      normal value (%FVC) was not changed in any of the three protocols. A significant
      increase in peak flow was observed in protocols B and C (P < 0.05). The maximal
      expiratory flow at 25% (V25) was not changed in any of the three protocols. PaO2
      was significantly increased and PacO2 was significantly decreased in protocol B
      (P < 0.01 and P < 0.05, respectively), whereas only PaCO2 was significantly
      decreased in protocol C (P < 0.05). Ejection fraction was increased in protocols
      B and C. These results suggest that exercise for a total period of 120 min/wk is
      preferable to that of 20 min/wk in COPD.

PMID- 9558018
TI  - Paranoia--an unusual presentation of hydrocephalus.
AB  - Hydrocephalus commonly occurs after traumatic brain injury. Normal pressure
      hydrocephalus after traumatic brain injury is usually associated with a failure
      to progress in therapy and a plateauing or regression of functional abilities.
      Behavior disturbances are commonly seen as unfortunate sequelae of traumatic
      brain injury. However, normal pressure hydrocephalus has not been reported to
      cause aberrant, antisocial behavior. This case report details the course of a
      patient who sustained a traumatic brain injury and, subsequently, developed
      normal pressure hydrocephalus associated with paranoia, delusions, and violent
      behavior.

PMID- 9558019
TI  - Chronic fatigue syndrome: a literature review from a physiatric perspective.
AB  - To examine the literature on chronic fatigue syndrome (CFS), especially as it
      relates to cognitive deficits and exercise, more than 200 articles related to CFS
      were selected from computer-based research as well as pertinent articles noted in
      the references of individual articles. All were relevant articles on CFS,
      although articles in a foreign language were excluded. CFS is a controversial
      diagnosis of exclusion, but certain subgroups do appear to exist. It may
      represent multiple diseases or multiple stages of the same disease. Although
      cognitive deficits are commonly reported, the measured impairments are relatively
      subtle and are in the area of complex information processing speed, or
      efficiency. Magnetic resonance imaging, single-photon emission computer
      tomography, and neuroendocrine studies present preliminary evidence suggestive of
      the cerebral involvement primarily in the white matter. The weakness and fatigue
      may be the result of alterations in the central nervous system, not in the
      peripheral muscles. However, it is hard to separate the documented weakness and
      endurance deficits from deconditioning. Autonomic symptoms such as orthostatic
      intolerance and a predisposition to neurally mediated syncope may be explained by
      cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or
      both. The review points out the need for more carefully designed studies of CFS
      that focus on the relationship between neuropathology, psychopathology and
      neuropsychologic functioning. The role of exercise as a stimulus for exacerbation
      or in treatment needs to be further studied using clear diagnostic criteria as
      well as control groups that carefully match the activity level.

PMID- 9558020
TI  - Biomagnetic 3-dimensional spatial and temporal characterization of electrical
      activity of human stomach.
AB  - Biomagnetic measurements are based on the noninvasive recording of magnetic
      signals produced by biological sources such as nervous system and muscle. The aim
      of this study was to obtain multichannel magnetic field recordings from the human
      gastrointestinal tract and to localize the sources of these signals three
      dimensionally. The magnetic field was recorded in eight human healthy subjects
      using a sensor array with 37 superconducting quantum interference devices
      (SQUIDs); an electrogastrogram was recorded simultaneously. Biomagnetic source
      localization was carried out with an iterative nonlinear optimization algorithm
      using the model of an equivalent current dipole (ECD) and correlated to magnetic
      resonance imaging (MRI) in four volunteers. Magnetogastrograms and
      electrogastrograms demonstrated a similar frequency distribution with a peak at
      3/min. In all subjects the centers of the calculated dipoles plotted vs time
      showed a characteristic migration across the stomach area. One volunteer
      demonstrated tachygastric episodes, during which his magnetic field amplitudes
      increased fivefold and his dipole migration disappeared. In absence of an attack
      his recordings changed to normal. This demonstrates multichannel magnetic
      recordings can be used to localize the sources of the biomagnetic field, which
      could be useful for the understanding of motility disturbances.

PMID- 9558021
TI  - Effect of local injection of botulinum toxin on sphincter of Oddi cyclic motility
      in dogs.
AB  - To study effects of intrasphincteric injections of botulinum toxin on the
      sphincter of Oddi cyclic motility and responses to motilin and cholecystokinin,
      four conscious dogs with duodenal cannula underwent manometry of the common bile
      duct, sphincter of Oddi, and duodenum. After baseline recording, each dog had
      intrasphincteric injections of saline or botulinum toxin. The injections of
      saline had no effect, whereas botulinum toxin significantly reduced mean basal
      pressure, amplitude, and motility index of the sphincter of Oddi. These effects
      took place in four to seven days and reached a maximum in seven to 10 days. The
      basal pressure returned to the baseline level in 28 weeks, but the amplitude and
      motility index remained low. The pressure parameters of motilin-induced premature
      phase III-like activity also decreased, but action of cholecystokinin was not
      affected. These results indicate that the botulinum toxin injections reduce
      sphincter of Oddi phasic contractile activity for a prolonged period of time.

PMID- 9558022
TI  - Small intestinal transit time and intraluminal pH in ileocecal resected patients
      with Crohn's disease.
AB  - The pH and transit times of the gut are important for the delivery of active drug
      from several tablets used in the treatment of Crohn's disease (CD). Many patients
      with CD undergo an ileocecal resection, which might influence small intestinal pH
      and transit time. The effect of ileocecal resection on these variables has not
      previously been studied. Intraluminal pH and transit time were measured in nine
      ileocecal-resected CD patients and 13 healthy volunteers using pH-sensitive
      radiocapsules. Small intestinal transit time (SITT) was significantly shorter in
      ileocecal-resected patients (5.2 hr, controls 8.0 hr). The pH levels of the small
      intestine were identical in patients and controls, whereas cecal pH was 0.9 pH
      units higher in resected CD patients. The time spent with pH higher than 5.5,
      6.0, 6.5, and 7.0 was significantly shorter in patients than in controls. There
      was no correlation between the SITT and the length of resected ileum or between
      the SITT and the time elapsed since the resection. We conclude that ileocecal
      resection decreases the SITT and the time with pH higher than 5.5-7.0. The study
      indicates that this reduction of the SITT is mainly due to the resection of the
      ileocecal valve and is, to a certain extent, independent of the length of
      resected ileum. An ileocecal resection might therefore affect the delivery of
      active drug from tablets with pH-dependent delivery.

PMID- 9558024
TI  - Polymorphism of motilin gene in patients with Crohn's disease.
AB  - An increasing body of evidence supports the concept of genetic heterogeneity
      within inflammatory bowel disease (IBD). In this study, a polymorphism of the
      motilin gene, which determines an amino acid substitution in the motilin protein,
      has been investigated in IBD patients. Fifty patients with ulcerative colitis
      (UC), and 52 with Crohn's disease (CD) were investigated for anti-neutrophil
      cytoplasmatic antibodies (ANCA) and the polymorphism in the second exon of the
      motilin gene. Sixty unrelated blood donors served as controls. ANCA were found in
      30% of UC and 13% of CD. In controls the DNA polymorphism identified two alleles
      (1 and 2) at a frequency of 42% and 58%, respectively. Patients with either UC or
      CD showed a slight increase in the frequency of allele 2 (69% and 60%,
      respectively; P > 0.05 vs controls). This allele was predominant in ANCA-positive
      CD patients (86%; P < 0.04) while in UC it did not differ. All ANCA-positive CD
      patients had the disease confined to the colon. A polymorphism of second exon of
      the motilin gene, leading to a protein variant, is significantly more frequent in
      the subset of ANCA-positive CD patients. This subgroup of patients appears to
      share peculiar genetic and clinical features.

PMID- 9558025
TI  - Refractory, disfiguring vulvar pyoderma gangrenosum and Crohn's disease.

PMID- 9558023
TI  - IL-10 synergizes with IL-4 and IL-13 in inhibiting lysosomal enzyme secretion by
      human monocytes and lamina propria mononuclear cells from patients with
      inflammatory bowel disease.
AB  - Tissue injury and inflammation in inflammatory bowel disease (IBD) are associated
      with enhanced monocytic lysosomal enzyme release. In this study, peripheral
      monocytes and lamina propria mononuclear cells (LPMNC) were isolated from IBD
      patients and normal controls. Cells were stimulated with lipopolysaccharide after
      treatment with IL-13, IL-4, and IL-10, and enzyme secretion was assessed by using
      the corresponding p-nitrophenyl glycosides as substrates. Molecular forms of
      cathepsin D were examined to describe the mode of enzyme release. IL-10 and IL-4
      strongly down-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a
      diminished responsiveness to the inhibitory effect of IL-13. Impaired monocyte
      response was not found with combinations of IL-13 and IL-10 or IL-4 and IL-10.
      LPMNC from involved IBD mucosa showed significantly higher enzyme secretion
      compared with LPMNC from noninvolved IBD mucosa but responded inefficiently to
      either IL-4, IL-13, or IL-10 alone. However, combined treatment with IL-10 and IL
      4 or IL-10 and IL-13 strongly suppressed enzyme release by these cells. Both the
      precursor and mature forms of cathepsin D were elevated in IBD patients. While IL
      13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both
      the precursor and mature form of cathepsin D. Our results favor the potent
      clinical utility of combined treatment, thus improving chances of developing
      effective treatments for human IBD.

PMID- 9558026
TI  - Increased prevalence of autoantibodies in celiac disease.
AB  - Several features suggest an immune mechanism operates in celiac disease.
      Information on the autoantibody repertoire in this condition is lacking. The
      purpose of the study was to investigate the reactivity of celiac patients sera to
      various autoantigens widely distributed in the human intestine. Seventy children,
      celiacs and controls, were evaluated for serum autoantibodies using ELISA and
      immunofluorescence. Celiac patients had increased prevalence of serum anti-single
      stranded DNA (14%), anti-double-stranded DNA (23%), anti-cardiolipin (14%), and
      anti-endomysial autoantibodies (63%). The relevance of this finding on the
      extraintestinal manifestations of celiac disease or the coexistence of autoimmune
      conditions and celiac disease remains to be determined.

PMID- 9558028
TI  - Effects of fiber laxatives and calcium docusate on regional water content and
      viscosity of digesta in the large intestine of the pig.
AB  - The aim of this study was to determine how bulk fibers and calcium docusate
      affect regional dehydration and digesta viscosity throughout the large intestine.
      Fifty-two pigs were fed a chow diet supplemented with a bulk laxative, placebo,
      or calcium docusate for three days, after which the pigs were sacrificed and the
      contents of the large bowel were analyzed. Digesta occurred as a continuum from
      liquid (cecum, 91.2% water content) to solid (rectum, 70.5% water content). The
      observed 20.7% difference in water content resulted in a 240-fold increase in
      viscosity. Half of this water is reabsorbed in the first 18% of the large bowel
      length where viscosity remains relatively low. Compared to placebo, calcium
      docusate and calcium polycarbophil had no significant effect on digesta water
      content or viscosity, polycarbophil exhibited significantly (P < 0.05) lower
      digesta viscosity in three bowel segments, and psyllium exhibited significantly
      (P < 0.01) lower viscosity in six bowel segments and higher water content in nine
      bowel segments. In conclusion, the majority of digesta dehydration occurs early
      in the proximal large bowel, while the greatest increases in viscosity occur in
      the distal bowel. Relatively small decreases in digesta water content result in
      large increases in digesta viscosity. Psyllium, and to a lesser extent
      polycarbophil, are able to resist dehydration, resulting in a softer digesta.

PMID- 9558027
TI  - Mast cell degranulation induces delayed rectal allodynia in rats: role of
      histamine and 5-HT.
AB  - Visceral hypersensitivity is a common feature of functional bowel disorders,
      where an increased number of mast cells have often been described. Thus, we
      investigated the effect of an experimental mast cell degranulation induced by BrX
      537A on somatic (tail heating) and visceral (rectal distension) sensitivity in
      rats and the involvement of histamine and/or serotonin on this last response.
      After BrX-537A administration, the latency of tail withdrawal reflex was
      shortened within the 2- to 8-hr period. Moreover, BrX-537A reduced the distension
      volume threshold from 0.8 ml to 0.4 ml inducing allodynia, from 6 to 12 hr after
      its administration. This effect was suppressed by doxantrazole (mast cell
      stabilizing agent) and WAY 100635 (5-HT1A receptor antagonist), and reproduced by
      5-HTP (5-HT precursor) and 8-OH-DPAT (5-HT1A receptor agonist). However, neither
      granisetron (5-HT3 receptor antagonist) nor H1, H2, or H3 histamine receptor
      antagonists modified the BrX-537A-induced allodynia. Consequently, mast cell
      degranulation initiates a delayed somatic and visceral allodynia, with the
      participation of serotonin, through 5-HT1A receptor activation, on the visceral
      response.

PMID- 9558029
TI  - Cytomegalovirus-induced gastrointestinal disease in previously healthy adults.

PMID- 9558030
TI  - Asymptomatic Helicobacter pylori gastritis is associated with increased sucrose
      permeability.
AB  - Our aim was to investigate whether there are changes in permeability to sucrose
      in asymptomatic Helicobacter pylori gastritis. Nineteen asymptomatic subjects
      with Helicobacter pylori-associated gastritis with no or mild mucosal atrophy and
      19 age- and sex-matched normal controls were studied by peroral load of sucrose
      (100 g). The fraction of the given oral dose of sucrose excreted in urine was
      increased in subjects with Helicobacter pylori gastritis (median 0.08% versus
      0.04% in controls). Sucrose excretion was not related to atrophy, intestinal
      metaplasia, or inflammation in the gastric mucosa. However, sucrose permeability
      was related to the degree of inflammatory (neutrophil) activity, since moderate
      activity was associated with higher sucrose excretion than mild activity (median
      0.13% vs 0.07%). Asymptomatic Helicobacter pylori gastritis was associated with
      an increased sucrose permeability, which could be a sign of gastric mucosal
      leakage. This could have implications for the diseases and complications
      associated with Helicobacter pylori infection.

PMID- 9558031
TI  - Pathological changes in the formation of Helicobacter pylori-induced gastric
      lesions in Mongolian gerbils.
AB  - We examined pathological changes in the formation of Helicobacter pylori-induced
      gastric lesions in Mongorian gerbils. H. pylori (NCTC11637) was orally
      administered once to the animals and was detected in the gastric mucosa of all
      gerbils given the bacteria. The number of viable H. pylori increased during the
      initial two weeks and thereafter reached a plateau level. The initial
      pathological changes were found at one week, ie, edema/congestion and a white
      viscous substance only in the antrum. At two weeks, superficial damage appeared
      in the antrum, although inflammatory cell infiltration had not occurred.
      Gastritis with lymphoid follicles was observed in the antrum and fundus from
      three weeks. At four weeks, mucosal lesions were detected as a few hemorrhagic
      spots in the fundus adjacent to the antrum. In the control animals, however, no
      pathological changes were observed even at four weeks. In the gastric mucosa
      infected with H. pylori, myeloperoxidase activity was negligible at two weeks,
      but was extremely elevated at four weeks. Similarly, neutrophil chemotactic
      activity was only slightly increased at two weeks, but was markedly elevated at
      four weeks. These results indicate that H. pylori infection induces initial
      pathological changes only in the antrum, but mucosal lesions occur in the fundus
      adjacent to the antrum. Furthermore, it is demonstrated that the initial
      superficial damage is generated by factors other than chemokines and neutrophil
      associated factors, although mucosal inflammation may contribute to the
      subsequent formation of lesions and ulcers.

PMID- 9558033
TI  - Prevalence of Helicobacter pylori infection in children from urban and rural West
      Virginia.
AB  - Our objective was to evaluate the prevalence rate of Helicobacter pylori (HP) in
      children from urban and rural areas of West Virginia. In all, 1164 blood samples
      were collected from children who attended a local health fair, pediatric clinics,
      and emergency departments of four different hospitals located in urban and rural
      counties. Socioeconomic status was determined in 303 children. Serum HP antibody
      (IgG) was measured by enzyme immunoassay (EIA). A total of 468 (40%) samples were
      HP positive. HP acquisition correlated with increasing age, family crowding, and
      community location (urban/rural) but not with gender, water source used
      (city/well), or socioeconomic status. The prevalence rate of HP in the children
      of West Virginia is higher than any data previously reported from the United
      States. The results correlated with only few socioeconomic criteria, suggesting
      that other factors may contribute to the increased prevalence of HP infection in
      the children of West Virginia.

PMID- 9558032
TI  - Low prevalence of Helicobacter pylori infection in patients with hamartomatous
      fundic polyps.
AB  - Helicobacter pylori infection of the gastric mucosal surface was investigated in
      patients with hamartomatous fundic polyps or hyperplastic polyps and in patients
      without endoscopic evidence of disease (healthy subjects). Presence of H. pylori
      infection was determined by culture, histologic examination, and the endoscopic
      phenol red test. Adherence of H. pylori was evaluated with scanning electron
      microscopic examination of antral biopsy specimens. Both prevalence of H. pylori
      infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients
      with hamartomatous fundic polyps than in healthy subjects and patients with
      hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa
      that contained IgA and of gastric epithelial cells that expressed Lewis b did not
      differ significantly among the three groups. These findings suggest that defense
      mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen
      are present in patients with hamartomarous fundic polyps.

PMID- 9558035
TI  - Phosphatidylcholine-associated aspirin accelerates healing of gastric ulcers in
      rats.
AB  - Based on our previous studies that aspirin (ASA) -induced gastric ulceration in
      rats can be significantly reduced if the drug is chemically associated with
      phosphatidylcholine (PC), we undertook the present study to compare gastric ulcer
      healing rates in rats administered either unmodified or PC-complexed ASA. Gastric
      ulcers were induced in anesthetized rats by briefly exposing the mucosal surface
      to 0.2 ml 60% acetic acid followed by randomization of the rats to study groups;
      daily intragastrically administered saline (control), ASA (36, 54 mg/kg), or ASA
      PC complex. In contrast to the 65-70% reduction in ulcer size recorded in
      controls, ulcer healing was significantly retarded in rats administered
      unmodified ASA. Conversely, the size of the experimentally induced ulcers was
      less than control values in rats daily administered the PC-associated ASA,
      suggesting an acceleration in the rate of ulcer healing. Daily intragastric
      administration of ASA to rats over the study period also resulted in a
      significant decrease in surface hydrophobicity from control values as measured by
      contact angle analysis. However, surface hydrophobicity was partially restored in
      rats administered the PC-complexed ASA. Consistent with these findings, it was
      determined that ASA-treated rats had a lower hematocrit than control values, as
      an index of gastrointestinal bleeding, whereas this parameter remained at control
      levels in rats administered the PC-complexed ASA. We conclude that PC-associated
      ASA promotes ulcer healing above the values measured in rats treated with ASA or
      saline. This property may be attributable to the fact that in contrast to
      unmodified ASA, which aggravates ulcer healing by transforming the stomach to an
      acid-permeable state, the protective hydrophobic lining of the stomach is
      maintained in rats administered PC-associated ASA, thereby allowing ulcer healing
      of the tissue to proceed.

PMID- 9558034
TI  - Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in
      the maintenance of healed gastric ulcer.
AB  - Our purpose was to compare the safety and efficacy of lansoprazole 15 mg and 30
      mg with placebo in preventing recurrence in 49 patients with a history of gastric
      ulcer. Within one month, 40% of patients receiving placebo experienced ulcer
      recurrence compared to 0% and 7% of patients receiving lansoprazole 15 mg and 30
      mg, respectively. All placebo patients became symptomatic, experienced ulcer
      recurrence or withdrew from the study by month 9. As compared to placebo, a
      significantly (P < 0.001) higher percentage of patients treated with lansoprazole
      15 mg (83%) and lansoprazole 30 mg (93%) with healed gastric ulcer disease
      remained healed at month 12. Of patients asymptomatic at baseline, 100% and 59%
      of those treated with lansoprazole 15 mg and 30 mg, respectively, remained
      asymptomatic at month 12. The incidence of adverse events was comparable among
      the treatment groups. Lansoprazole safely and effectively reduces ulcer
      recurrence in patients with a history of gastric ulcer disease.

PMID- 9558036
TI  - Gastroduodenal mucosal protection induced by dehydroleucodine: mucus secretion
      and role of monoamines.
AB  - In previous work we have demonstrated that dehydroleucodine (DhL) prevents
      gastric damage induced by necrosis-inducing agents such as absolute ethanol
      (EtOH). In this study we examine the effects of DhL on gastroduodenal morphology
      and monoamine levels by histological and biochemical methods, respectively, as an
      approach to elucidating the cytoprotective mechanism of the drug. Histological
      evidence shows that DhL prevents formation of gastroduodenal mucosal lesions
      induced by EtOH and that this protective effect is related to the ability of the
      drug to stimulate mucus production. DhL itself does not affect the tissue
      concentration of NE, DA and 5-HT. However, it prevents the depletion of DA and 5
      HT provoked by EtOH. We propose that the abundant mucoid blanket secreted after
      treatment with DhL acts as a diffusion barrier against EtOH. It is also possible
      that DhL could act as a "cell stabilizer," by inhibiting the degranulation of
      cells containing monoamines.

PMID- 9558037
TI  - Inhibition of human gastric lipase secretion by glucagon-like peptide-1.
AB  - Glucagon-like peptide-1 (GLP-1) may be one of the enterogastrone hormones of the
      ileal brake mechanism. We therefore studied its effects on gastric lipase
      secretion in healthy volunteers and vagotomized patients during infusion of
      pentagastrin. The intestinal incretin hormone GLP-1 (glucagon-like peptide-1, 7
      36 amide) was investigated because of its inhibitory effects on gastric acid
      secretion and motility. GLP-1 infused intravenously in amounts corresponding to
      the postprandial release significantly inhibited pentagastrin-stimulated gastric
      lipase secretion and lipolytic activity. The inhibitory effect of GLP-1 persisted
      in vagotomized patients, suggesting that fundic chief cells, from which gastric
      lipase is released, or neighboring inhibitory cells could be equipped with GLP-1
      receptors. Vagotomized patients had significantly higher plasma concentrations of
      gastrin and secretin. No significant changes of gastrin, secretin, and CCK
      secretion were seen during GLP-1 infusion in the vagotomized patients, whereas
      secretin decreased significantly in the healthy volunteers. GLP-1 seems to be a
      naturally occurring inhibitor of gastric lipase secretion acting via a nonvagal
      mechanism. Our results indicate that gastric lipase secretion is subject to
      hormonal stimulatory as well as inhibitory mechanisms.

PMID- 9558038
TI  - Adaptive cytoprotection against deoxycholate-induced injury in human gastric
      cells in vitro: is there a role for endogenous prostaglandins?
AB  - The majority of previous work investigating adaptive cytoprotection has involved
      in vivo studies, which have suggested that this protective response is in large
      part mediated by endogenous prostaglandins (PGs). The aim of this study was to
      investigate adaptive cytoprotection under in vitro conditions in human gastric
      cells and to better delineate the role of endogenous PGs in this protective
      response. AGS cells (a human gastric carcinoma cell line) were characterized
      morphologically and subsequently used for all experiments. Sodium deoxycholate
      was used as both the mild irritant and the damaging agent, and cell injury was
      quantified using both a commercial viability/cytotoxicity kit as well as
      transepithelial permeability studies. Finally, endogenous PG synthesis in
      response to varying concentrations of deoxycholate was determined. AGS cells were
      determined to be morphologically similar to gastric mucous cells. Pretreatment of
      cells with low-dose deoxycholate significantly attenuated injury upon subsequent
      exposure to damaging concentrations of deoxycholate, and this protection was
      determined to be dependent upon both concentration and duration of mild irritant
      exposure. Preincubation of AGS cells with indomethacin reversed protection
      induced by mild irritant pretreatment and also significantly increased cellular
      susceptibility to injury. Results of the permeability studies closely paralleled
      those assessing cell mortality. While deoxycholate exposure increased PG
      synthesis, the concentrations required were much higher than those needed to
      initiate protection. Adaptive cytoprotection exists in AGS cells under in vitro
      conditions independent of intact blood flow, neural innervation, or circulating
      humoral mediators. While this protection is reversed by indomethacin, it appears
      that this reversal results from increased cellular injury secondary to diminished
      basal PGs, rather than inhibition of endogenous PG synthesis.

PMID- 9558039
TI  - Gastroprotection by 4-methylpyrazole against ethanol in humans.
AB  - 4-Methylpyrazole (4-MP), a specific inhibitor of alcohol dehydrogenase, exerts
      gastroprotection of unusually long duration in rats. We tested the hypothesis
      that pretreatment with 4-MP might protect the human gastric mucosa against
      alcohol-induced acute injury. Fourteen healthy volunteers received pretreatment
      with either 4-MP, 15 mg/kg body weight dissolved in 50 ml of orange juice, or
      placebo and 2 hr later 100 ml of 40% ethanol. The endoscopic appearance of the
      gastric mucosa was evaluated and scored (scale 0-5) and mucosal biopsies were
      obtained just before pretreatment and 30 min after ethanol for histologic
      examination and prostaglandin E2 measurement. In the 4-MP group the mean
      endoscopic injury score was significantly lower than that in placebo group, in
      both the body and the antrum. Histologically, 4-MP significantly reduced
      disruption of surface epithelium and completely prevented the deep hemorrhagic
      mucosal lesions. In the 4-MP group no changes in gastric mucosal PGE2 levels were
      detected. In rats, 4-MP did not inhibit gastric acid output, whereas it markedly
      increased the adherent gastric mucus evaluated by the alcian blue recovery
      method. When lipid peroxidation was induced by carbon tetrachloride in hepatic
      microsomes, 4-MP caused significant inhibition of malondialdehyde generation. We
      conclude that 4-MP provides significant protection of the human stomach against
      alcohol-induced acute mucosal injury. 4-MP, besides inhibiting the conversion of
      alcohol to acetaldehyde, might protect the gastric mucosa by increasing adherent
      gastric mucus and by scavenging free radicals.

PMID- 9558040
TI  - Bombesin prevents gastric injury in the rat: role of gastrin.
AB  - Bombesin or gastrin-releasing peptide prevents gastric injury by an unknown
      mechanism. Since exogenous gastrin is a gastroprotective agent, this study was
      undertaken to test the hypothesis that gastroprotection by bombesin involves
      release of endogenous gastrin. Subcutaneous bombesin (10-100 microg/kg) dose
      dependently reduced macroscopic injury to the acid-secreting portion of the
      stomach caused by 1 ml of orogastric acidified ethanol (150 mM hydrochloric acid
      50% ethanol). Blockade of type A cholecystokinin receptors with intraperitoneal
      MK-329 (1 mg/kg) reversed intravenous cholecystokinin (5 nmol/kg)-induced
      gastroprotection, but not that of bombesin. In contrast, intraperitoneal type B
      cholecystokinin (gastrin) receptor blockade with L-365,260 (25 mg/kg) diminished
      the protective actions of both subcutaneous bombesin (100 microg/kg) and
      intravenous gastrin (25 pmol/kg). In additional studies, subcutaneous bombesin
      (10-100 microg/kg) dose dependently increased serum gastrin levels
      (radioimmunoassay). Both the gastroprotective actions of bombesin and bombesin
      induced gastrin release were enhanced following immunoneutralization of
      endogenous somatostatin with intraperitoneal somatostatin antibody (2 mg). These
      data indicate that bombesin prevents gastric injury primarily by release of
      endogenous gastrin and both effects are modified by endogenous somatostatin.

PMID- 9558041
TI  - Impact of ingested liquids on 24-hour ambulatory pH tests.
AB  - A prospective investigation of the impact of ingested liquids on 24-hr pH test
      scores was conducted. Eighty-two patients contributed 142 samples. The liquids
      used were coffee/tea (N = 35), water (N = 32), fruit juice (N = 29), cola (N =
      34), and beer (N = 12). The pH of cola, juice, and beer are approximately 3.0.
      The parameters studied included: total test time, total drink time, total minutes
      of pH < 4.0 during drink, minutes of < pH 4.0 10 min before drink, and minutes of
      pH < 4.0 10 min following drink. Analysis was performed using one-way ANOVA and
      repeated measures. Age of patients, total test time, and total time pH < 4.0 were
      not significantly different (P > 0.05). The total time to consume the drink was
      significantly greater (P < 0.05) for beer than all other liquids. The total time
      (7.7 +/- 6.0 min) pH < 4.0 for cola was significantly different (P < 0.023) than
      beer (3.3 +/- 3.7 min), tea/coffee (1.4 +/- 6.5 min), and water (1.1 +/- 2.5
      min). The percentage of total time pH < 4.0 was not significantly different (P >
      0.05) among any of the liquids. The percentage of time pH < 4.0 during the drink
      was the highest for cola (63 +/- 47%) and juice (51 +/- 57%); water, coffee/tea,
      and beer were not significantly different (P > 0.05). Although the impact of cola
      and juice were the greatest, none of these had an impact that exceeded 0.5%. The
      lack of impact of beer appears to be due to the increased period of time it takes
      to consume. We conclude that the impact of ingested fluids is minimal and can
      probably be disregarded in most patient groups.

PMID- 9558043
TI  - Concurrent fluoroscopy and manometry reveal differences in laparoscopic Nissen
      and anterior fundoplication.
AB  - A prospective double-blind randomized trial was initiated to examine two types of
      laparoscopic fundoplication (Nissen and anterior). Thirty-two patients with
      proven gastroesophageal reflux disease presenting for primary laparoscopic
      antireflux surgery were randomized to undergo either Nissen fundoplication (N =
      13) or anterior hemifundoplication (N = 19). Postoperative fluoroscopic and
      manometric examination was carried out concomitantly. Nissen fundoplication
      resulted in significantly greater elevation of resting (33.5 vs 23 mm Hg) and
      residual lower esophageal sphincter pressures (17 vs 6.5 mm Hg) and lower
      esophageal ramp pressure (26 vs 20.5 mm Hg) than the anterior partial
      fundoplication. A smaller radiologically measured sphincter opening diameter was
      seen following Nissen fundoplication (9 mm) compared with anterior fundoplication
      (12 mm). Lower esophageal ramp pressure correlated weakly (r = 0.37, P = 0.04)
      with postoperative dysphagia. It is concluded that the type of fundoplication
      performed significantly influences postoperative manometric and video barium
      radiology outcomes. The clinical relevance of this requires further
      investigation.

PMID- 9558042
TI  - Effect of amino acids on lower esophageal sphincter characteristics and
      gastroesophageal reflux in humans.
AB  - The effect of a commercially available mixed amino acids solution, when given
      either intravenously or intragastrically, on lower esophageal sphincter (LES)
      pressure, frequency of transient LES relaxations (TLESRs) and gastroesophageal
      reflux (GER) was investigated in six healthy volunteers. LES pressure and
      esophageal pH were simultaneously recorded on three separate occasions 1 hr
      before (basal) and 3 hr during intravenous or intragastric infusion of amino
      acids (250 mg protein/kg/hr) or saline (control). No significant changes in LES
      pressure were seen in the control experiment. Intravenous amino acids caused a
      rapid and sustained (P < 0.01) decrease in LES pressure whereas intragastric
      amino acids decreased LES pressure only gradually and temporarily (P < 0.01). In
      the three experiments no significant differences were observed in TLESR
      frequency, the number of GER episodes, the mechanism of reflux, or duration of
      acid exposure. In healthy subjects both intragastric and, especially, intravenous
      infusion of amino acids significantly decrease LES pressure but do not affect the
      frequency of TLESRs or GER episodes during a continuous liquid gastric load.

PMID- 9558044
TI  - Most Helicobacter pylori-infected patients have specific antibodies, and some
      also have H. pylori antigens and genomic material in bile: is it a risk factor
      for gallstone formation?
AB  - Bile may contain a 130-kDa protein endowed with aminopeptidase activity and the
      ability to promote cholesterol crystallisation. As >90% of H. pylori strains have
      a similar peptidase activity, and half the isolates express a 110- to 140-kDa
      antigen, the CagA protein, we investigated a possible association between H.
      pylori infection and gallstones, and the presence in bile samples of factors
      related to H. pylori that could increase cholesterol crystallization. The
      prevalence of H. pylori infection was 82.1% in 112 patients with gallstones and
      80.3% in 112 controls (NS). Fifteen bile samples out of 23 specimens from
      infected patients (65.2%) contained anti-CagA antibodies. A approximately 60-kDa
      antigen only reacting with an anti-CagA antibody was found in five bile samples
      (21.7%) from 23 infected patients. One bile sample (4.1%) contained ureA and cagA
      genes of H. pylori. The homology of CagA with the N-terminal sequence of
      aminopeptidase N was very low. We concluded that the presence of specific
      antibody to H. pylori in most bile samples tested and of an H. pylori putative
      antigen in a discrete number of cases may represent factors that increase the
      risk of gallstone formation.

PMID- 9558045
TI  - Intracellular calcium affects neutrophil chemoattractant expression by
      macrophages in rats with cerulein-induced pancreatitis.
AB  - Pancreatitis complicated with infection often results in the development of
      multiple organ failure. We investigated the role of altered intracellular calcium
      as a priming signal for cytokine-induced neutrophil chemoattractant expression in
      this process. Agents modulating cytosolic Ca2+ were utilized to study the in vivo
      and in vitro cytokine-induced neutrophil chemoattractant expression for
      macrophages in rats with cerulein-induced pancreatitis after intraperitoneal
      administration of lipopolysaccharide as a septic challenge. Pretreatment with the
      calcium channel blocker verapamil significantly reduced serum cytokine-induced
      neutrophil chemoattractant concentrations in rats with cerulein-induced
      pancreatitis after septic challenge. Lipopolysaccharide-stimulated in vitro
      cytokine-induced neutrophil chemoattractant (CINC) production by peritoneal
      macrophages was significantly enhanced by pretreatment with thapsigargin (an
      inhibitor of the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187
      (a calcium-specific ionophore, extracellular Ca2+ influx). Pretreatment with
      U73122 (a phospholipase C inhibitor) inhibited lipopolysaccharide-stimulated but
      not basal cytokine-induced neutrophil chemoattractant production, while verapamil
      (a calcium channel blocker), TMB-8 (an inhibitor of calcium release from
      endoplasmic reticulum), and W7 (calmodulin antagonist) completely abrogated the
      chemoattractant production. Altered intracellular calcium, due to Ca2+ efflux
      from intracellular stores, may be involved in the "priming" of macrophages to
      release cytokine-induced neutrophil chemoattractant following triggering with
      lipopolysaccharide during acute cerulein pancreatitis.

PMID- 9558046
TI  - Lymphoepithelial cyst of the pancreas: a case report and review of the
      literature.

PMID- 9558047
TI  - Analysis of human T-cell antigen receptor variable beta gene usage following
      vaccination with recombinant HBsAg.
AB  - We analyzed the TcR Vbeta gene usage before and after vaccination with the
      hepatitis B vaccine since changes in the TcR Vbeta gene families would be
      considered to provide preliminary evidence of a mechanism to prevent HBV
      infection. Six healthy adult volunteers received immunizations. TcR Vbeta usage,
      T-cell proliferation, and HLA class II alleles were examined in peripheral blood
      mononuclear cells (PBMC) both before and after vaccination. Furthermore, TcR
      Vbeta usage in postimmunization PBMC was also compared with PBMC cultured with
      recombinant HBsAg (rHBsAg). The level of in vitro T-cell proliferation in the
      presence of rHBsAg increased significantly (P < 0.01) in PBMC isolated after
      vaccinations. Increases in the different TcR Vbeta genes were also observed in
      each individual following vaccinations, regardless of the similarity in their HLA
      alleles. Specific HBV-related antigen-responsive T cells were induced after HB
      vaccination, without any common restriction for the TcR Vbeta gene families. The
      mechanism that helps prevent HBV infection was thus found to involve multiclonal
      alterations in the TcR Vbeta repertoire.

PMID- 9558048
TI  - Ultrastructural study of development of hepatic necrosis induced by TNF-alpha and
      D-galactosamine.
AB  - Recent studies have suggested an association between tumor necrosis factor-alpha
      (TNF-alpha) and the development and progression of acute liver failure. To
      investigate the role of TNF-alpha in the mechanism of massive hepatic necrosis,
      we studied a mouse model of TNF-alpha and D-galactosamine (GalN) -induced hepatic
      necrosis by ultrastructural analysis. Administration of GalN caused edema of
      hepatocellular microvilli and widening of sinusoidal endothelial fenestrae (SEF);
      administration of TNF-alpha caused only a widening of the SEF. Massive hepatic
      necrosis with hemorrhage was seen 6 hr after concomitant administration of TNF
      alpha and GalN. In the ultrastructural analysis, edema of the hepatocellular
      microvilli, widening of the SEF, and transmigration of red blood cells (RBC) and
      platelets to the space of Disse without exfoliation and necrosis of the
      sinusoidal endothelial cells were observed. Fibrin deposits were seen in areas
      adjacent to injured hepatocytes. The diameter of the SEF was significantly
      greater than in the nontreated group and the groups treated with TNF-alpha or
      GalN alone. These results suggest that as a consequence of the increase in
      diameter of the SEF, transmigration of RBCs and platelets to the space of Disse
      may have resulted in massive hepatic necrosis due to occlusion of the
      microcirculation.

PMID- 9558049
TI  - Chronic splanchnic hemodynamic effects of spironolactone with unrestricted sodium
      diet in patients with compensated cirrhosis.
AB  - The purpose of this study is to determine the hemodynamic effects of
      spironolactone administration associated with an unrestricted sodium diet (salt
      10 g) in patients with compensated cirrhosis and portal hypertension. We studied
      the hemodynamic changes following eight weeks of administration of either placebo
      (N = 6) or spironolactone (100 mg/day) (N = 6 Pugh-Child's A and 6 B). No
      significant changes were observed after the administration of the placebo.
      Spironolactone induced a significant reduction in the hepatic venous pressure
      gradient (HVPG) (-10.1 +/- 13.3%, P < 0.05), which was associated with a
      significant reduction of cardiac output (-11.5 +/- 9.3%, P < 0.01), plasma volume
      (-8.1 +/- 4.7%, P < 0.01), and wedged hepatic venous pressure (-10.5 +/- 11.6%, P
      < 0.05). There was no significant change in hepatic blood flow and there was no
      significant correlation between the change in the HVPG and the change in
      circulating plasma volume. A decrease in the HVPG greater than 10% was observed
      in eight of 12 patients (67%), defined as responders, at eight weeks. Six of six
      (100%) grade A patients and two of six (33%) grade B patients responded. This
      study demonstrated that spironolactone with an unrestricted sodium diet decreased
      the HVPG in grade A patients but did not significantly decrease the HVPG in grade
      B patients.

PMID- 9558050
TI  - Gastric cancer occurring at anastomosis after gastrojejunostomy without
      gastrectomy.

PMID- 9558051
TI  - Adenocarcinoma of the upper esophagus arising in cervical ectopic gastric mucosa:
      rare evidence of malignant potential of so-called "inlet patch".

PMID- 9558052
TI  - Polypoid ganglioneuroma of colon.

PMID- 9558053
TI  - The history of the Southwestern Surgical Congress: 1949-1998. Introduction.

PMID- 9558054
TI  - 50 years of abdominal surgery at the Southwestern Surgical Congress: common
      problems and uncommon surgeons.

PMID- 9558055
TI  - 50 years of thoracic and cardiac surgery at the Southwestern Surgical Congress:
      from tuberculosis to the artificial heart.

PMID- 9558056
TI  - 50 years of vascular surgery at the Southwestern Surgical Congress: evolution of
      a new specialty.

PMID- 9558057
TI  - 50 years of breast, endocrine, and oncologic surgery at the Southwestern Surgical
      Congress: earlier diagnosis and improved outcomes.

PMID- 9558058
TI  - 50 years of trauma, burns, and surgical critical care at the Southwestern
      Surgical Congress.

PMID- 9558059
TI  - 50 years of general surgery at the Southwestern Surgical Congress.

PMID- 9558060
TI  - CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal
      murine leishmaniasis.
AB  - Synthetic oligodeoxynucleotides containing CpG dinucleotides (CpG-ODN) mimic the
      immunostimulatory qualities of bacterial DNA. We asked whether immunostimulation
      by CpG-ODN predisposes for a commitment toward a Th1 vs a Th2 response in
      Leishmania major infection, a model for a lethal Th2-driven disease, in BALB/c
      mice. CpG-ODN induced Th1 effector T cells in vitro and conveyed protective
      immunity to disease-prone BALB/c mice in vivo. Conversion to a Th1-driven
      resistant phenotype was associated with IL-12 production and maintained the
      expression of IL-12R beta2-chains. Most strikingly, CpG-ODN were even curative
      when given as late as 20 days after lethal L. major infection, indicating that
      CpG-ODN revert an established Th2 response. These findings imply an important
      role of bacterial DNA and CpG-ODN in the instruction of adaptive immune
      responses. They also point to the therapeutic potential of CpG-ODN in redirecting
      curative Th1 responses in Th2-driven disorders.

PMID- 9558061
TI  - Predictable TCR antigen recognition based on peptide scans leads to the
      identification of agonist ligands with no sequence homology.
AB  - The potential of CD4+ T cells for cross-recognition of self and foreign Ags has
      important implications for the understanding of thymic selection, lymphocyte
      survival, and the occurrence of autoimmune diseases. Here, we define the
      extensive flexibility of Ag recognition for three human CD4+ autoreactive T cell
      clones (TCC) by using ligands with single and multiple amino acid (aa)
      substitutions. Our results demonstrate that the spectrum of tolerated ligands and
      the resulting stimulatory potency of peptides for a TCC can be predicted by the
      relative influence of each aa. Using this approach, we have identified
      stimulatory ligands not sharing a single aa in corresponding positions with the
      Ag used to establish the TCC. These results argue for an independent contribution
      of each aa in the peptide sequence to the affinity of the MHC/peptide complex to
      the TCR.

PMID- 9558062
TI  - Liposomal formulation of a self lymphoma antigen induces potent protective
      antitumor immunity.
AB  - We developed a liposome carrier for a model nonimmunogenic, self Ag. This carrier
      reproducibly converted lymphoma Ig into a potent tumor rejection Ag in mice. A
      single immunization induced protection against challenges representing 20 to 100
      times the minimum lethal dose of parental tumor. This protective effect required
      minimal amounts of incorporated Ag and IL-2 and elicited specific Abs (compared
      with free Ag or liposomal control Ig which did not elicit any specific Abs);
      depletion experiments demonstrated a requirement for effector CD4+ and CD8+ T
      cells. Head-to-head comparisons, indicating superior potency and induction of
      specific T cell activation, distinguished liposomal from prototype, carrier
      conjugated Ag. These results provide a strategy for formulating weak tumor or
      other clinically important Ags into vaccines.

PMID- 9558063
TI  - IL-12 and IL-18 differentially regulate the transcriptional activity of the human
      IFN-gamma promoter in primary CD4+ T lymphocytes.
AB  - We analyzed the molecular mechanisms by which IL-12 and IL-18 induce
      transcriptional activity of the IFN-gamma promoter in primary human CD4+ T cells.
      In transfection experiments, we found that IL-18 directly induces IFN-gamma
      promoter activity, whereas significant activation with IL-12 required
      costimulation with alphaCD3/CD28. Furthermore, IL-12 caused in vivo protection of
      a STAT4 (-236) binding site, whereas stimulation with IL-18 or IL-12 plus
      alphaCD3/CD28 induced occupancy of a downstream AP-1 site. Mutation of this AP-1
      site abrogated both IL-12- and IL-18-mediated promoter activation, whereas
      mutation of the STAT site inhibited IL-12-dependent activation. These data
      suggest that both AP-1 and STAT4 are required for IL-12-dependent IFN-gamma
      promoter activity, whereas IL-18 causes direct activation via AP-1. This
      differential activation of the IFN-gamma promoter gives further insights into
      molecular pathways governing Th1 T cell development and differentiation.

PMID- 9558064
TI  - Thymic lineage commitment rather than selection causes genetic variations in size
      of CD4 and CD8 compartments.
AB  - During their development, immature CD4+ CD8+ thymocytes become committed to
      either the CD4 or CD8 lineage. Subsequent complete maturation of CD4+ and CD8+
      cells requires a molecular match of the expressed coreceptor and the MHC
      specificity of the TCR. The final size of the mature CD4+ and CD8+ thymic
      compartments is therefore determined by a combination of lineage commitment and
      TCR-mediated selection. In humans and mice, the relative size of CD4+ and CD8+
      peripheral T cell compartments shows marked genetic variability. We show here
      that genetic variations in thymic lineage commitment, rather than TCR-mediated
      selection processes, are responsible for the distinct CD4/CD8 ratios observed in
      common inbred mouse strains. Genetic variations in the regulation of lineage
      commitment open new ways to analyze this process and to identify the molecules
      involved.

PMID- 9558065
TI  - T:T antigen presentation by activated murine CD8+ T cells induces anergy and
      apoptosis.
AB  - Using an IL-2-secreting, noncytolytic, H-Y-specific, CD8+ T cell clone, the
      functional consequences of Ag presentation by T cells to T cells were
      investigated. Incubation of the T cells with H-Y-soluble peptide led to
      nonresponsiveness to Ag rechallenge. This was due to the simultaneous induction
      of apoptosis, involving approximately 40% of the T cells, and of anergy in the
      surviving cells. These effects were strictly dependent upon bidirectional T:T
      presentation, in that exposure of C6 cells to peptide-pulsed T cells from the
      same clone induced proliferation but not apoptosis or anergy. The inhibitory
      effects of T:T presentation were not due to a lack of costimulation, since the T
      cells expressed levels of CD80 and CD86 higher than those detected on cultured
      dendritic cells and equipped them to function as efficient APCs for primary CD8+
      T cell responses. Following incubation with soluble peptide, CD80 expression
      increased, and high levels of CTLA-4 (CD152) expression were induced. Although
      addition of anti-CTLA-4 Ab augmented proliferation in response to soluble
      peptide, no protection from apoptosis or anergy was observed. Neither Fas nor TNF
      alpha was expressed/produced by the C6 cells, and coligation of MHC class I
      molecules and TCR failed to reproduce the effects of T:T presentation. Taken
      together, these data suggest that T:T Ag presentation induces anergy and
      apoptosis in murine CD8+ T cells and may reflect the regulatory consequences of
      T:T interactions in the course of clonal expansion in vivo.

PMID- 9558066
TI  - Identification of a developmentally regulated phase of postselection expansion
      driven by thymic epithelium.
AB  - To investigate events following the initiation of positive selection, we have
      used reaggregate organ cultures to follow the maturation of purified CD4+8+69+
      thymocytes; these thymocytes represent a subpopulation of thymocytes which have
      already received positive selection signals. Using a dilution analysis of an FITC
      based membrane-binding dye, 5-(and -6)-carboxyfluorescein diacetate succinimidyl
      ester, to allow a quantitative measure of proliferation, we show that while newly
      selected CD4+ and CD8+ cells are nondividing, both subsets subsequently undergo a
      wave of postpositive selection proliferation involving multiple cell divisions.
      Moreover, in the presence of fetal stromal cells, postselection expansion is more
      extensive in newborn thymocytes compared with adult thymocytes, suggesting that
      this phase of expansion is developmentally regulated. We also show that
      proliferation of CD4+ and CD8+ cells is seen in reaggregates of purified MHC
      class II+ thymic epithelial cells, while CD4+ and CD8+ cells generated from bcl-2
      transgenic CD4+8+69+ thymocytes in the absence of stromal cell support survive
      but do not proliferate; this observation indicates that MHC class II+ thymic
      epithelial cells are both necessary and sufficient to mediate this wave of cell
      division. Finally, the maturation of CD4+8+69+ thymocytes and the subsequent
      proliferation of CD4+ and CD8+ cells occur in the presence of MHC-mismatched
      thymic stromal cells, suggesting that the later stages of positive selection and
      the associated postselection events do not depend on interactions with the same
      peptide/MHC complexes responsible for initiation.

PMID- 9558067
TI  - CD8+ cells are not necessary for allograft rejection or the induction of
      apoptosis in an experimental model of small intestinal transplantation.
AB  - Allospecific CTL can function as cellular effectors of solid organ graft
      rejection; however, the specific mechanisms of cell damage remain undetermined.
      In this study we examined the role of CD8+ T cells in apoptosis and rejection of
      small intestinal allografts. ACI rat intestinal grafts transplanted into Lewis
      rat recipients showed apoptosis of epithelial crypt cells on day 3 posttransplant
      as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end labeling staining. By day 7 numerous apoptotic crypt cells
      were detected in allografts, but were rarely observed in FK506-treated allograft
      recipients, isografts, or native intestine of allograft recipients. To further
      investigate the mechanism of rejection, recipient rats were depleted of CD8+
      cells by treatment with OX-8 mAbs the day before and the day after
      transplantation of rat small intestinal allografts. Depletion of CD8+ cells from
      allograft recipients did not alter the tempo or the histologic features of
      rejection compared with those in the control (IgG-treated) group. Moreover, there
      was no difference in the number of apoptotic crypt epithelial cells in the grafts
      of control and CD8-depleted rats. Reverse transcriptase-PCR analyses determined
      there were similar levels of transcripts for Fas, Fas ligand, perforin, and
      granzyme B in control and CD8-depleted allograft recipients. By Western blot it
      was determined that the levels of Fas ligand protein were increased in the CD8
      depleted group compared with those in control and FK506-treated allograft
      recipients. These data suggest that CD8 cells are not required for tissue injury
      or apoptotic cell death in small intestine allograft rejection.

PMID- 9558068
TI  - Mouse CD1-autoreactive T cells have diverse patterns of reactivity to CD1+
      targets.
AB  - Humans and mice contain significant populations of T cells that are reactive for
      autologous CD1 molecules. Using a panel of five mouse CD1 (mCD1)-autoreactive T
      cell hybridomas, we show here that this autoreactivity does not correlate with
      the level of CD1 expression. In some cases, these autoreactive T cells can
      distinguish between different cell types that express the same CD1 molecule,
      suggesting that some factor in addition to CD1 expression is critical for
      autoreactive T cell stimulation. To determine whether a CD1-bound ligand may be
      required, we expressed mutant mCD1 molecules that are defective for the putative
      endosomal localization sequence in the cytoplasmic domain. We demonstrate that
      mCD1, like its human CD1 homologues, is found in endosomes, and that it
      colocalizes extensively with the DM molecule. We further demonstrate, by site
      directed mutagenesis, that the tyrosine in the cytoplasmic sequence is required
      for this endosomal localization. A T cell hybrid expressing Vbeta8 and Valpha14,
      the major TCR expressed by NK1+ T cells, exhibited greatly diminished reactivity
      to mutant CD1 molecules that do not traffic through endosomes, although the
      reactivity of other T cell hybrids to this mutant was not greatly affected.
      Therefore, we propose that at least some of the autoreactive T cells require
      endosomally derived CD1-bound ligands, and that they are capable of
      distinguishing between a diverse set of such self-ligands, which might be either
      autologous lipoglycans or peptides.

PMID- 9558069
TI  - Phorbol esters induce differentiation of human CD34+ hemopoietic progenitors to
      dendritic cells: evidence for protein kinase C-mediated signaling.
AB  - The intracellular signals that mediate the differentiation of pluripotent
      hemopoietic progenitors to dendritic cells (DC) are largely undefined. We have
      found that the phorbol ester PMA by itself induced 47% +/- 8.7% of input human
      CD34+ hemopoietic progenitors to differentiate into cells with morphology and
      surface Ag phenotype characteristic of DC by day 7 of culture. Functionally, PMA
      generated DC processed and presented whole soluble Ag and also induced resting T
      cell proliferation and Ag-specific CTL effector function. Unlike cytokine-driven
      DC differentiation, PMA suppressed proliferation and induced cell death (in part
      via apoptosis) in cells that did not differentiate to DC. The effects of PMA were
      blocked by inhibitors of protein kinase C activation, suggesting a central role
      for this signaling molecule. PMA-mediated signaling also induced expression of
      the RelB transcription factor, an NF-kappaB family member implicated in DC
      differentiation. These findings suggest that phorbol esters activate protein
      kinase C, which then initiates the terminal component of an intracellular
      signaling pathway(s) involved in the DC differentiation of CD34+ hemopoietic
      progenitors.

PMID- 9558070
TI  - Modulation of naive CD4 T cell activation with altered peptide ligands: the
      nature of the peptide and presentation in the context of costimulation are
      critical for a sustained response.
AB  - Altered peptide ligands containing single amino acid substitutions have the
      potential to be used for modulating immune function. Using a panel of moth
      cytochrome c peptides, we demonstrate that different phases of naive CD4 T cell
      response are alternately modulated depending on altered peptide ligand dose and
      accessory molecule expression by APC. Weak agonists presented at high
      concentration, and with costimulation, efficiently induced early phase naive T
      cell activation as assessed by IL-2R/CD69 expression, but could only promote
      sufficient IL-2 for a short-lived proliferative response. In contrast, strong
      agonists and heteroclitic peptides induced early phase T cell activation even at
      low concentrations with costimulation, and allowed sustained IL-2 secretion and
      proliferation. In the absence of accessory molecule help, early and late phase
      activation was impaired with weak agonists, whereas strong agonists partially
      compensated for a lack of costimulation for early phase activation, and also
      promoted enhanced IL-2 with sustained proliferation. These studies support the
      hypothesis that the naive T cell response will be determined by the balance
      between provision of accessory molecule help and the affinity of peptide/MHC
      complexes for individual TCRs, and suggest that extended IL-2 production is the
      main facet of naive CD4 activation that is affected by altering the nature of the
      peptide.

PMID- 9558071
TI  - MHC class I is required for peripheral accumulation of CD8+ thymic emigrants.
AB  - MHC molecules influence the fate of T lymphocytes at two important stages of
      their differentiation. Recognition of self peptide/MHC complexes in the thymus
      determines whether immature T cells should live and mature into immunocompetent T
      cells or whether they should die. In the periphery, recognition of Ags presented
      by MHC molecules induces T cell activation, proliferation, and differentiation
      into effector/memory T cells. We describe in this work a third role that MHC
      molecules play in T cell physiology. CD8+ thymic emigrants require presence of
      MHC class I molecules in the periphery to seed the peripheral lymphoid organs.
      Numbers of CD8+ T cells are reduced severely in both the thymus and the periphery
      of beta2-microglobulin-deficient (beta2m[-/-]) mice. When grafted with wild-type
      (beta2m[+/+]) thymic epithelium, immature beta2m(-/-) T cells that populate the
      graft develop into functional mature CD8+ cells. However, significant numbers of
      peripheral CD8+ cells in grafted beta2m(-/-) mice can be observed only after
      injection of MHC class I-expressing cells in the periphery. Thus, naive T cells
      in the periphery do not passively await antigenic stimulation, but actively
      engage in interactions with self MHC molecules that may promote their survival.

PMID- 9558072
TI  - IFN-gamma receptor deletion prevents autoantibody production and
      glomerulonephritis in lupus-prone (NZB x NZW)F1 mice.
AB  - (NZB x NZW)F1 female (BW) mice spontaneously develop an autoimmune disease,
      characterized by the production of autoantibodies (autoAbs) and
      glomerulonephritis, which can be delayed by neutralizing IFN-gamma Abs and
      accelerated by IFN-gamma injections. To define the role of IFN-gamma in the
      pathogenesis of glomerulonephritis, we established a population of BW mice
      deficient in IFN-gammaR (BWgammaR[-/-]) by repeated crossing; these mice were
      compared with BWgammaR(+/+) and +/- littermates. Of the BWgammaR(+/+) and +/-
      mice, 50% showed immune complex glomerulonephritis with heavy proteinuria at 8 mo
      of age, while only 10% of the BWgammaR(-/-) mice were affected at 14 mo. The
      serum concentration of anti-dsDNA and anti-histone Abs was dramatically reduced
      in BWgammaR(-/-) mice. The role of IFN-gamma in promoting class switch to IgG2a
      and IgG3 could not fully account for the impaired production of anti-dsDNA in
      BWgammaR(-/-) animals since, IgM and IgG1 levels were also reduced. There was a
      high incidence of B cell lymphoma in the BWgammaR(-/-) mice, which might be
      related to the suppression of autoAb production. Thus, the absence of
      glomerulonephritis in BWgammaR(-/-) mice is likely due to a dramatic yet
      unexplained effect of the inactivation of IFN-gamma signaling on autoAb
      production.

PMID- 9558073
TI  - Cross-reactivity in murine fluoroquinolone photoallergy: exclusive usage of TCR
      Vbeta13 by immune T cells that recognize fluoroquinolone-photomodified cells.
AB  - Fluoroquinolone antibacterial agents are well known to elicit photosensitivity as
      an adverse effect, and their cross-reactivity has been clinically documented. The
      photoallergenicity of fluoroquinolones is mainly derived from their photohaptenic
      moiety, and photomodification of skin epidermal cells with fluoroquinolones is
      thought to be an initial step for this photoallergy. Here we have explored, both
      in vivo and in vitro, T cell responses to fluoroquinolone-photomodified cells,
      focusing on their photoantigenic cross-reactivity. Cells were derivatized with
      fluoroquinolones under exposure to UV-A, and fluoroquinolone photoadducts were
      detected in photomodified cells by immunostaining, flow cytometry, and cell ELISA
      using fluoroquinolone-specific mAb. T cell-mediated hypersensitivity induced and
      elicited by s.c. injection of fluoroquinolone-photomodified epidermal cells was
      cross-reactive among six fluoroquinolones. In addition, lymph node cells from
      mice sensitized with fluoroquinolone-photomodified cells proliferated well in
      vitro not only to Langerhans cell-enriched epidermal cells photoderivatized with
      corresponding fluoroquinolone, but also to those photomodified with any of five
      other fluoroquinolones, supporting their cross-reactivity. In three
      fluoroquinolones tested, Th1 populations that expanded after in vitro
      photoantigenic stimulation of immune lymph node cells expressed the same Vbeta13
      of TCR. The sensitivity could be transferred by the i.v. administration of this
      Vbeta13+ T cell line into naive recipients, in which a high percentage of
      Vbeta13+ cells infiltrated at the challenge site. These findings suggest that
      these fluoroquinolones carry the same photoantigenic epitope, which is recognized
      by Vbeta13+ T cells, leading to fluoroquinolone photosensitivity and cross
      reactivity.

PMID- 9558074
TI  - Reprogramming of lipopolysaccharide-primed macrophages is controlled by a
      counterbalanced production of IL-10 and IL-12.
AB  - We studied the potential role of a cytokine regulatory mechanism(s) in LPS
      dependent reprogramming and modulation of TNF-alpha and nitric oxide (NO)
      responses in mouse peritoneal macrophages. Reciprocal regulation of TNF-alpha and
      NO production by LPS-primed and LPS-stimulated macrophages was found to be
      dependent on the presence of soluble secretory products released by the cells
      during the initial LPS priming interaction. Pretreatment of naive macrophages
      with different mouse recombinant cytokines such as rIL-10, rIL-12, and rIFN-gamma
      dose dependently and differentially regulated subsequent LPS-induced production
      of TNF-alpha, IL-6, and NO by cytokine-primed cells. Analysis of IL-12 and IL-10
      levels present in culture supernatants of LPS-primed and LPS-stimulated
      macrophages revealed a high degree of correlation between the profiles of TNF
      alpha and IL-12 as well as NO and IL-10. Furthermore, LPS priming of macrophages
      in the presence of anti-IL-12-neutralizing mAb attenuated TNF-alpha responses
      while at the same time up-regulated NO production. In contrast, neutralization of
      endogenous IL-10 with anti-IL-10 mAb resulted in considerable TNF-alpha response
      at LPS priming doses under conditions that would otherwise strongly inhibit TNF
      alpha production. We also found that the initial LPS priming of naive macrophages
      differentially and dose dependently regulates expression of mRNAs for IL-10, IL
      12, and IFN-gamma in LPS-primed macrophages. Collectively, our data provide
      experimental support for the hypothesis that a cytokine regulatory network, most
      probably autocrine, tightly controls the reciprocal modulation of TNF-alpha and
      NO responses in LPS-primed macrophages.

PMID- 9558075
TI  - TCR usage by homocysteine-specific human CTL.
AB  - We have recently demonstrated that homocysteine can modify HLA class I Ags and
      induce homocysteine-specific CTL (Hom-CTL) responses in humans. Here, we have
      investigated TCR usage by Hom-CTL from five patients with ankylosing spondylitis
      or reactive arthritis. TCR of HLA-A68-restricted Hom-CTL from two unrelated
      donors share the same TCR Valpha, Vbeta, and Jbeta gene segments (AV4, BV23, and
      BJ2S1, respectively) with similar third complementarity determining regions
      (CDR3) of the beta-chains. Interestingly, the Va and Vbeta gene segments employed
      by an HLA-B27-restricted Hom-CTL clone are also closely related to AV4 and BV23,
      indicating strong selection pressure for AV4, BV23, and related gene products in
      the homocysteine-specific TCR. An arginine or lysine residue frequently appeared
      at position alpha93 in the CDR3 of the TCR alpha-chains from Hom-CTL restricted
      by HLA-A68 or -B8. This may suggest a potential salt bridge between the carboxyl
      group of homocysteine and specific TCR. TCR usage by HLA-B27-restricted Hom-CTL
      from unrelated individuals appears to be less conserved, although two T cell
      clones from one individual rearranged the same V gene segments with identical
      lengths of CDR3. Implications of these data for the molecular mechanisms for
      homocysteine modification of HLA Ags are also discussed.

PMID- 9558076
TI  - Bcmd decreases the life span of B-2 but not B-1 cells in A/WySnJ mice.
AB  - Peripheral B cells are divided into two subpopulations, B-1 and B-2, the
      relationship of which remains obscure. We recently showed that the Bcmd mutation
      in A/WySnJ mice reduces average B cell life span, yielding 90% fewer peripheral B
      cells. Despite this defect, A/WySnJ mice have an elevated proportion of
      peritoneal CD5+ B cells, suggesting that Bcmd may be the first B-cell-intrinsic
      gene to differentially affect the B-1 and B-2 subpopulations. To test this
      hypothesis in detail, we have used in vivo BrdU labeling and four-color
      cytofluorometry to examine the numbers and turnover rates of sIgM+CD23-CD43+ (B
      1) and sIgM+CD23+CD43- (B-2) splenocytes in A/WySnJ and A/J mice. The results
      show the expected 90% reduction of splenic B-2 cells among A/WySnJ mice, but a
      normal splenic B-1 cell pool. Increased B-1 cell renewal cannot explain this
      undiminished pool, because BrdU labeling kinetics reveals an identical splenic B
      1 subset turnover rate of approximately 4%/day in both A/WySnJ and A/J strains.
      Thus, B-1 cells are Bcmd-independent but B-2 cells are Bcmd-dependent, suggesting
      Bcmd functions in a positive signaling pathway that imparts longevity to
      quiescent B cells, but that is not required for cycling B cells. Moreover these
      results show that the requisites for maturation and longevity differ between the
      B-1 and B-2 subsets.

PMID- 9558077
TI  - Generation of the germline peripheral B cell repertoire: VH81X-lambda B cells are
      unable to complete all developmental programs.
AB  - The generation of VH81X heavy chain lambda-light chain-expressing B cells (VH81X
      lambda+ B cells) was studied in VH81X heavy chain transgenic mice as well as in
      VH81X JH (-/-) and VH81X JH (-/-) Ck (-/-) mice, in which competition resulting
      from expression of heavy and light chains from the endogenous heavy and kappa
      light chain loci was prevented. We show that although lambda light chain gene
      rearrangements occur normally and give rise to light chains that associate with
      the transgenic heavy chain to form surface and soluble IgM molecules, further B
      cell development is almost totally blocked. The few VH81X-lambda+ B cells that
      are generated progress into a mature compartment (expressing surface CD21, CD22,
      CD23, and low CD24 and having a relatively long life span) but they also have
      reduced levels of surface Ig receptor and express higher amounts of Fas Ag than
      VH81X-kappa+ B cells. These VH81X-lambda+ B cells reach the peripheral lymphoid
      organs and accumulate in the periarteriolar lymphoid sheath but are unable to
      generate primary B cell follicles. In other heavy chain transgenic mice (MD2,
      M167, and M54), lambda+ B cells are generated. However, they seem to be
      preferentially selected in the peripheral repertoire of some transgenic heavy
      chain mice (M54) but not in others (MD2, M167). These studies show that a crucial
      selection step is necessary for B cell survival and maintenance in which B cells,
      similar to T cells, receive signals depending on their clonal receptors.

PMID- 9558078
TI  - Differential capacities of CD4+, CD8+, and CD4-CD8- T cell subsets to express IL
      18 receptor and produce IFN-gamma in response to IL-18.
AB  - IL-12 and IL-18 have the capacity to stimulate IFN-gamma production by T cells.
      Using a T cell clone, we reported that IL-18 responsiveness is generated only
      after exposure to IL-12. Here, we investigated the induction of IL-18
      responsiveness in resting CD8+, CD4+, and CD4-CD8- T cells. Resting T cells
      respond to neither IL-12 nor IL-18. After stimulation with anti-CD3 plus anti
      CD28 mAbs, CD8+, CD4+, and CD4-CD8- T cells expressed IL-12R, but not IL-18R, and
      produced IFN-gamma in response to IL-12. Cultures of T cells with anti-CD3/anti
      CD28 in the presence of rIL-12 induced IL-18R expression and IL-18-stimulated IFN
      gamma production, which reached higher levels than that induced by IL-12
      stimulation. However, there was a substantial difference in the expression of IL
      18R and IL-18-stimulated IFN-gamma production among T cell subsets. CD4+ cells
      expressed marginal levels of IL-18R and produced small amounts of IFN-gamma,
      whereas CD8+ cells expressed higher levels of IL-18R and produced more IFN-gamma
      than CD4+ cells. Moreover, CD4-CD8- cells expressed levels of IL-18R comparable
      to those for CD8+ cells but produced IFN-gamma one order higher than did CD8+
      cells. These results indicate that the induction of IL-18R and IL-18
      responsiveness by IL-12 represents a mechanism underlying enhanced IFN-gamma
      production by resting T cells, but the operation of this mechanism differs
      depending on the T cell subset stimulated.

PMID- 9558079
TI  - Fas/Fas ligand signaling during gestational T cell development.
AB  - Most thymocytes express high levels of Fas Ag (Apo-1/CD95); however, the role of
      Fas/Fas ligand-mediated apoptosis in thymocyte development remains unclear.
      During gestational development of thymocytes in C57BL/6(B6) +/+ mice, the highest
      levels of Fas ligand mRNA and Fas ligand protein expression were detected at
      gestational day (GD) 15, and there was a ninefold decrease in Fas ligand mRNA
      expression between GD 15 and 17 accompanied by a sixfold increase in Fas mRNA.
      Apoptotic thymocytes were first detected in the medulla at GD 15, and increasing
      numbers of cortical clusters and scattered, single apoptotic cells were present
      on GD 16 and 17. Thus, early apoptosis correlated with high expression of Fas
      ligand. High levels of Fas ligand mRNA were maintained throughout gestational
      development in thymocytes of Fas-deficient B6-lpr/lpr mice, but cortical clusters
      and scattered apoptotic cells were decreased relative to B6 +/+ mice before GD
      17. Kinetic analysis of fetal thymic organ cultures treated with anti-Fas Ab
      demonstrated that thymocytes become sensitive to Fas-mediated apoptosis during
      the transition from the CD4-CD8- to the CD4+CD8+ phenotype. More mature CD4+CD8+
      thymocytes and CD4+ and CD8+ thymocytes became resistant to Fas-mediated
      apoptosis after GD 17, despite high expression of Fas. However, low avidity
      engagement of the TCR on Fas-sensitive CD4+CD8+ thymocytes before GD 17 induced
      resistance to Fas-mediated apoptosis. The present results indicate that Fas plays
      a critical role in mediating apoptosis during early gestational thymocyte
      development and that thymocytes that receive a survival signal through TCR/CD3
      become resistant to Fas-mediated apoptosis.

PMID- 9558080
TI  - The actin-bundling protein fascin is involved in the formation of dendritic
      processes in maturing epidermal Langerhans cells.
AB  - Dendritic cells (DC) are characterized by their unique potential to prime naive T
      cells. Epidermal Langerhans cells (LC), the DC resident in the epidermis, gain
      this immunostimulatory capacity following Ag contact in vivo or during in vitro
      culture of epidermal cell suspensions. To analyze differential gene expression in
      maturing LC, we constructed a highly representative cDNA library of cultivated LC
      (cLC) in lambda ZAP II containing 18 x 10(6) independent clones. This library was
      screened with freshly isolated Langerhans cell (fLC)- and cLC-derived probes for
      cLC-specific cDNAs. The cDNAs identified were sequenced and analyzed by database
      searches. Two cDNA fragments were identified as fragments of fascin, indicating
      that fascin is differentially expressed in LC. By competitive RT-PCR, we
      confirmed that fascin is highly expressed in cLC cultivated for 1, 2, and 3 days,
      while no signals were obtained with fLC. Western blot and immunofluorescence
      analysis revealed cLC-specific expression of fascin on the protein level as well.
      Fascin is known to be involved in the organization of the actin cytoskeleton in
      cytoplasmatic extensions of nerve growth cones. Its differential expression in
      maturing LC coincides with the formation of numerous dendritic projections in LC.
      Their formation was inhibited by incubation of LC with fascin antisense
      oligonucleotides during cultivation. Therefore, we conclude that fascin is
      necessary for the formation of the dendritic processes of maturing Langerhans
      cells and may thus influence T cell-LC interaction.

PMID- 9558081
TI  - A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for
      UV-induced systemic immune suppression.
AB  - Even though all of the energy contained with the UV wavelengths of solar
      radiation is absorbed within the epidermis and upper layers of the dermis, UV
      irradiation can suppress immune responses to Ag introduced at distant
      nonirradiated sites. In addition, data from a number of laboratories have
      suggested that one consequence of UV exposure is suppressed Th1 cell activation
      with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like
      phenotype. Cytokines secreted by UV-irradiated keratinoctyes, particularly IL-10,
      have been shown to play a major role in the induction of systemic immune
      suppression and differential activation of T helper cell subsets. Although IL-10
      can influence Th1 cell activation by altering Ag presentation and suppressing IFN
      gamma secretion, the major signal for the development of a Th2 response is IL-4.
      Here we tested the hypothesis that UV irradiation induces IL-4 secretion. UV
      irradiation induced serum IL-4 in a dose-dependent fashion. Injecting UV
      irradiated mice with anti-IL-4 blocked immune suppression. We could find no
      evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes.
      Rather, we suggest that prostaglandins released by irradiated keratinocytes
      induce serum IL-4 since treating UV-irradiated mice with a cyclooxygenase-2
      inhibitor blocked its production. Moreover, we found that treating UV-irradiated
      mice with anti-IL-4 suppressed serum IL-10 levels. In addition, injecting normal
      mice with PGE2 induced serum IL-4 and IL-10. We suggest that UV exposure
      activates a cytokine cascade (PGE2 --> IL-4 --> IL-10) that ultimately results in
      systemic immune suppression.

PMID- 9558082
TI  - Antiviral cytotoxic activity across a species barrier in mixed xenogeneic
      chimeras: functional restriction to host MHC.
AB  - Reconstitution of lethally irradiated mice with a mixture of mouse and rat bone
      marrow cells (mouse + rat-->mouse) results in mixed xenogeneic chimerism and
      donor-specific tolerance. The current study demonstrates that mouse and rat T
      lymphocytes that have developed in xenogeneic chimeras are restricted to Ag
      presentation by mouse, but not rat, APC. Restriction to host Ags results in
      functional immunocompetence with generation of antiviral cytotoxic activity in
      vivo, within and across species barriers. These data demonstrate for the first
      time that the host thymus is sufficient to support development and positive
      selection of functional cross-species T lymphocytes. The superior
      immunocompetence, as compared with fully xenogeneic (rat-->mouse) chimeras, may
      prove to be of significant benefit in the clinical application of
      xenotransplantation to solid organ transplantation and immune reconstitution for
      AIDS.

PMID- 9558083
TI  - Potent apoptotic signaling and subsequent unresponsiveness induced by a single
      CD2 mAb (BTI-322) in activated human peripheral T cells.
AB  - Manipulation of CD2 molecules with CD2 mAb pairs has been shown to deliver
      apoptotic signals to activated mature T cells. We show that BTI-322, a CD2 mAb
      directed at a peculiar epitope of CD2, can trigger on its own the apoptotic death
      of IL-2-activated peripheral T cells and of OKT3-stimulated T cells, contrasting
      in this respect with a series of other mouse or rat CD2 mAb. F(ab')2 fragments
      were as potent as the whole Ab. BTI-322-induced apoptosis proceeded in a few
      hours and was independent of the Fas/Fas ligand system. Less than 5 ng/ml of BTI
      322, added at the beginning of culture, were able to eliminate within 4 days most
      CD3+ cells from OKT3- and IL-2-stimulated lymphocytes, the only cells remaining
      being CD16+CD2- NK cells. T cell proliferative responses induced by a mitogenic
      CD2 mAb pair or by PHA-P (which mainly binds to CD2) were not inhibited by BTI
      322. In this case, the apoptotic effect was successfully counteracted by
      simultaneous enhancement of T cell divisions. Thus, the killing effect of BTI-322
      was most effective when T cells were exclusively stimulated through the CD3/TCR
      complex. Apoptosis of the responding T cells may explain why T cells recovered
      from a primary MLC performed in the presence of BTI-322 responded to third party
      cells but not to the primary stimulatory cells. These data constitute the
      rational basis for the use of BTI-322 for inducing tolerance in human
      allotransplantation.

PMID- 9558084
TI  - Transgenic expression of Fas in T cells blocks lymphoproliferation but not
      autoimmune disease in MRL-lpr mice.
AB  - Fas is a member of the TNF receptor family. Binding of Fas ligand to Fas induces
      apoptosis in Fas-bearing cells. Fas is expressed in various cells, including
      thymocytes, peripheral T cells, and activated B cells. The mouse lpr mutation is
      a loss of function mutation of Fas. MRL-lpr/lpr mice develop lymphadenopathy and
      splenomegaly, and produce multiple autoantibodies, which results in autoimmune
      disease. In this report, we describe the establishment of a line of Fas
      transgenic MRL-lpr mice in which mouse Fas cDNA was expressed using the T cell
      specific murine lck promoter. The transgenic mice expressed functional Fas in
      thymocytes and peripheral T cells, but not in B cells. The transgenic mice did
      not accumulate abnormal T cells (Thy-1+ B220+), but still accumulated B cells
      (Thy-1- B220+); they produced a large quantity of Igs (IgG1 and IgG2a), including
      anti-DNA Abs, and developed glomerulonephritis. These results suggest that
      autoreactive or activated B cells must be killed through Fas expressed in the B
      cells by the Fas ligand expressed in activated T cells.

PMID- 9558085
TI  - Critical roles of glycosaminoglycan side chains of cartilage proteoglycan
      (aggrecan) in antigen recognition and presentation.
AB  - Systemic immunization of BALB/c mice with proteoglycan (aggrecan) from fetal
      human cartilage induces progressive polyarthritis, an experimental disease
      similar to human rheumatoid arthritis. The development of the disease in this
      genetically susceptible murine strain is based on cross-reactive immune responses
      between the immunizing fetal human and mouse self-proteoglycans. One of the cross
      reactive and arthritogenic T cell epitopes (92GR/QVRVNSA/IY) is localized in the
      G1 domain of human/murine proteoglycan. Susceptible BALB/c mice, however, develop
      arthritis only if both the chondroitin sulfate (CS) and keratan sulfate (KS) side
      chains of the arthritogenic human proteoglycans are removed. The function of
      these two glycosaminoglycan side chains is opposite. The presence of a KS side
      chain in adult proteoglycan inhibits the recognition of arthritogenic T cell
      epitopes, prevents the development of T cell response, and protects animals from
      autoimmune arthritis. In contrast, the depletion of the CS side chain generates
      clusters of CS stubs and provokes a strong B cell response. These carbohydrate
      specific B cells are the most important proteoglycan APC. Taken together,
      proteoglycan-induced progressive polyarthritis is dictated by three major
      components: genetic background of the BALB/c strain, highly specific T cell
      response to epitope(s) masked by a KS chain in aging tissue, and the presence of
      proteoglycan (CS stub)-specific B cells required for sufficient Ag presentation.

PMID- 9558086
TI  - Increasing immunogenicity of antigens fused to Ig-binding proteins by cell
      surface targeting.
AB  - Fusion of antigenic proteins to Ig-binding proteins such as protein A from
      Staphylococcus aureus and its derived ZZ fragment is known to increase
      immunogenicity of the fused Ag in vivo. To shed light on the origin of this
      effect, we used snake toxins as Ags and observed that 1) fusion of toxins to ZZ
      enhanced their presentation to a toxin-specific T cell hybridoma (T1B2), using
      A20 B lymphoma cells, splenocytes, or peritoneal exudate cells as APCs; 2) this
      enhancement further increased when the number of fused Ig-binding domains varied
      from two with ZZ to five with protein A; and 3) the phenomenon vanished when the
      fusion protein was preincubated with an excess of free ZZ or when P388D1
      monocytes cells were used as APCs. Therefore, ZZ-fused toxins are likely to be
      targeted to surface Igs of APCs by their ZZ moiety. Furthermore, ZZ-alpha and
      toxin alpha stimulated similar profiles of toxin-specific T cells in BALB/c mice,
      suggesting a comparable processing and presentation in vivo for both toxin forms.
      To improve the targeting efficiency, ZZ-alpha was noncovalently complexed to
      various Igs directed to different cell surface components of APCs. The resulting
      complexes were up to 10(3)-fold more potent than the free toxin at stimulating
      T1B2. Also, they elicited both a T cell and an Ab response in BALB/c mice,
      without the need of any adjuvant. This simple approach may find practical
      applications by increasing the immunogenicity of recombinant proteins without the
      use of adjuvant.

PMID- 9558087
TI  - Differential requirement for p56lck in fetal and adult thymopoiesis.
AB  - The protein tyrosine kinase p56lck is critical for the generation of mature
      thymocytes in adult mice. However its requirement during the maturation of
      thymocytes from the fetal to the adult stage has not been clearly defined. We
      analyzed prenatal and postnatal thymocyte maturation in mice deficient for p56lck
      (lck[-/-]). Before birth, lck appears to play a crucial role in the expansion and
      proliferation of CD4+CD8+ double positive thymocytes, whereas proliferation and
      absolute numbers of CD4-CD8- double negative thymocyte precursors remained within
      the normal range until the end of the second week postnatal. Three weeks after
      birth, the total numbers of double negative and immature single positive
      thymocytes underwent a dramatic reduction that correlated with a decrease in the
      double positive population. This ontogenic defect was associated with a
      significant decrease in the proliferation rates of thymocyte precursors. Our data
      suggest that signaling via p56lck kinase is differentially required within a
      given phenotypically defined thymocyte subpopulation, depending on its stage of
      thymocyte maturation.

PMID- 9558088
TI  - Nuclear factor kappaB is required for peptide antigen-induced differentiation of
      a CD4+CD8+ thymocyte line.
AB  - NF-kappaB transcription factors are known to regulate the expression of a number
      of genes involved in T cell activation and function. Some evidence has suggested
      that they also play a role in T cell development. However, the role of NF-kappaB
      in Ag-induced thymocyte differentiation has not been directly addressed to date.
      Here we critically examine this role by employing DPK, a CD4+CD8+ thymocyte line
      that undergoes differentiation upon TCR engagement in a process that closely
      mimics positive selection. Expression of a degradation-resistant form of
      IkappaBalpha in DPK cells results in constitutive inhibition of NF-kappaB
      activity. We find that in the absence of NF-kappaB activity, MHC-peptide-induced
      differentiation of DPK is blocked. Furthermore, differentiation induced by a
      nonphysiologic stimulus, anti-TCR Ab, is greatly reduced. Altogether, our data
      indicate a requirement for NF-kappaB in the developmental changes associated with
      positive selection.

PMID- 9558089
TI  - Thymic alterations induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are strictly
      dependent on aryl hydrocarbon receptor activation in hemopoietic cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related congeners affect the
      immune system, causing immunosuppression and thymic atrophy in a variety of
      animal species. TCDD is believed to exert its effects primarily through the
      ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR).
      Although the AhR is found at high levels in both thymocytes and thymic stroma, it
      is uncertain in which cells TCDD is activating the AhR to cause alterations in
      the thymus. Some investigators have suggested that stromal elements, primarily
      epithelial cells, within the thymus are the primary targets for TCDD. Others have
      suggested that atrophy is due to a direct effect on thymocytes, either by
      apoptosis or by altering the development of progenitor cells. By producing
      chimeric mice with TCDD-responsive (AhR[+/+]) stromal components and TCDD
      unresponsive (AhR[-/-]) hemopoietic components, or the reverse, we have clarified
      the role of stromal vs hemopoietic elements in TCDD-induced thymic alterations.
      Our results show that the targets for TCDD-induced thymic atrophy and phenotypic
      alterations are strictly in the hemopoietic compartment and that TCDD activation
      of epithelial cells in the stroma is not required for thymic alterations.
      Furthermore, changes observed in the putative stem cell populations of these
      chimeric mice are also dependent on TCDD activation of the AhR in hemopoietic
      elements.

PMID- 9558090
TI  - CTLA-4 regulates tolerance induction and T cell differentiation in vivo.
AB  - Cytotoxic T lymphocyte Ag-4 (CTLA-4; CD152) is an important T cell regulatory
      molecule. In vitro experiments have shown that the blockade of signals through
      CTLA-4 augments T cell expansion, while CTLA-4 cross-linking results in decreased
      T cell proliferation due to decreased IL-2 production. However, less is known
      about the role of CTLA-4 in regulating an ongoing immune response. In this study,
      we examined the role of CTLA-4 in the expansion, decline, tolerization, and
      differentiation of T cells following treatment with staphylococcal enterotoxin B
      (SEB). Anti-CTLA-4 treatment resulted in increased numbers of SEB-reactive T
      cells and blockade of subsequent tolerance induction. Further examination of the
      SEB-reactive cells from anti-CTLA-4-treated mice demonstrated that both the CD4+
      and CD8+ Vbeta8+ T cells produced IL-4, providing evidence that not only do
      signals through CTLA-4 regulate T cell-tolerizing events, but they also play an
      important role in the differentiation of T cells in vivo.

PMID- 9558091
TI  - Mouse cell surface antigens: nomenclature and immunophenotyping.
AB  - This paper reviews cell surface Ags expressed on mouse hemopoietic and
      nonhemopoietic cells. The review will cover molecules included in the cluster of
      differentiation (CD) from CD1 to CD166 and lymphocyte Ag (Ly) series from Ly-1 to
      Ly-81 as well as some new Ags without current CD or Ly assignments. In addition
      to an update on mouse nomenclature, there will be a discussion of some known
      functions of the molecules and brief comments on the use of particular Ags for
      immunophenotyping of cell subsets. Several novel markers mentioned may prove
      useful in mouse immunology research.

PMID- 9558092
TI  - Selective inhibition of expression of the chemokine receptor CCR2 in human
      monocytes by IFN-gamma.
AB  - IFN-gamma is a potent activator of mononuclear phagocyte function and promotes
      the development of Th1 responses. Moreover, it induces and modulates chemokine
      production in a variety of cell types, including mononuclear phagocytes. In the
      present study, we examined the effect of IFN-gamma on the expression of CC
      chemokine receptors in human monocytes. IFN-gamma selectively and rapidly
      inhibited expression of the monocyte chemotactic protein (MCP) receptor CCR2 with
      an ED50 of approximately 50 U/ml. The effect was rapid (detectable after 1 h) and
      reversible. Other chemokine receptors (CCR1, CCR3, CCR4, and CCR5) were not
      substantially affected, and CXCR4 was reduced. IFN-gamma acted in concert with
      LPS, TNF-alpha, and IL-1beta in inhibiting CCR2 expression. IFN-gamma-treated
      monocytes showed a shorter half-life of CCR2 mRNA compared with untreated cells,
      whereas the rate of nuclear transcription was unaffected. The inhibition of CCR2
      mRNA expression by IFN-gamma was associated with a lower number of surface
      receptors and lower chemotactic responsiveness. Thus, IFN-gamma, an inducer of
      MCP-1 and MCP-3 in mononuclear phagocytes, selectively inhibits expression of the
      MCP receptor CCR2 in monocytes. These results are consistent with an emerging
      paradigm of divergent regulation by several agents of chemokine production and
      receptor expression in monocytes. The inhibition of MCP-1R expression may serve
      as a means of retaining mononuclear phagocytes at sites of inflammation and as a
      feedback mechanism in the regulation of recruitment from the blood.

PMID- 9558093
TI  - Characterization of Oct2 from the channel catfish: functional preference for a
      variant octamer motif.
AB  - The Ig heavy chain enhancer of the channel catfish (Ictalurus punctatus) has an
      unusual position and structure, being found in the 3' region of the mu gene and
      containing eight functional octamer motifs of consensus (ATGCAAAT) and variant
      sequences. The presence of multiple octamer motifs suggests that an Oct2
      homologue may play an important role in driving expression of the Ig heavy chain
      locus in a teleost fish. To test this hypothesis, two catfish Oct2 cDNAs (alpha
      and beta) were cloned by screening a catfish B cell cDNA library. Catfish Oct2
      alpha and beta isoforms are derived by alternative RNA splicing; as determined by
      Southern analysis, Oct2 is a single copy gene. In comparisons with mammalian
      Oct2, the catfish Oct2 isoforms show high sequence conservation in their N
      terminal regions and POU domains, but extensive divergence in their C-terminal
      regions. Catfish Oct2 a and beta are tissue restricted, bind both consensus and
      variant octamer motifs, and activate transcription in both catfish and murine
      cells. In contrast, mouse Oct2 activated transcription in mouse but not catfish
      cells. Catfish Oct2 beta is a more potent transcriptional activator than Oct2
      alpha. In transient expression assays, catfish Oct2 beta showed a marked
      preference for the octamer variant, ATGtAAAT, which occurs twice in the catfish
      enhancer. Mouse Oct2 also showed increased activity with the variant octamer when
      tested in mouse B cells. Gel-shift analysis competition assays indicated that
      catfish Oct2 binds the consensus octamer motif with an apparently higher affinity
      than it does the variant motif.

PMID- 9558094
TI  - Posttranslational regulation of TCR Valpha allelic exclusion during T cell
      differentiation.
AB  - We have previously shown that phenotypic allelic exclusion of TCR alpha-chain is
      functional only in mature thymocytes. A significant proportion of immature
      thymocytes (TCRlow) express more than one cell surface alpha-chain, but mature
      thymocytes (TCRhigh) show phenotypic allelic exclusion and express only a single
      alpha-chain. We have analyzed thymocytes for both surface and intracellular alpha
      chain expression and find that the majority of mature thymocytes express a second
      alpha-chain intracellularly. This result is predicted by a model in which the
      developmentally regulated allelic exclusion of the TCR alpha-chain is caused by
      competition between alpha-chains for the beta-chain rather than by models in
      which one alpha-chain is down-regulated or in which selection favors cells with
      only a single alpha-chain species. Changes in the relative amounts of alpha- and
      beta-chains available for pairing may therefore allow competition between the two
      alpha-chains for the beta-chain. Peripheral T cells also frequently express
      second alpha-chains in the cytoplasm (18-27%), despite a rather low frequency of
      dual alpha-chain expression on the cell surface (2-4%). The frequency of
      nonsurface expressed alpha-chains is reduced somewhat compared with thymocytes,
      indicating that an additional level of control of allelic exclusion operates
      during the maturation of peripheral T cells.

PMID- 9558095
TI  - Extracellular HIV-1 Tat protein induces the rapid Ser133 phosphorylation and
      activation of CREB transcription factor in both Jurkat lymphoblastoid T cells and
      primary peripheral blood mononuclear cells.
AB  - Extracellular HIV-1 Tat protein (0.1-100 ng/ml) induced a rapid (peak at 30 min)
      increase in the Ser133 phosphorylation levels of the transcription factor CREB in
      serum-starved Jurkat cells, as revealed by Western blot and indirect
      immunofluorescence analyses. Nuclear cAMP-responsive element (CRE) binding
      activity in electrophoretic mobility shift assays was constitutive in
      unstimulated Jurkat cells, showing only a small increase upon Tat treatment.
      However, transient transfection experiments performed with various
      chloramphenicol acetyl-transferase (CAT) constructs showed that Tat produced a
      fourfold induction of CAT activity only in the presence of a CRE-dependent CAT
      construct. Moreover, the use of plasmids encoding for GAL4-CREB fusion proteins
      demonstrated that Tat induction of pG4-CAT reporter gene required the CREB moiety
      of the GAL4-CREB fusion protein and that Ser133 CREB was essential for Tat
      activity. Extracellular Tat also stimulated Ser133 CREB phosphorylation in
      freshly isolated PBMC; this effect was completely blocked by either staurosporin,
      a broad-spectrum inhibitor of various protein kinases, or PD 98059, a specific
      inhibitor of mitogen-activated protein kinases (MAPK). Furthermore, extracellular
      Tat induced a rapid (peak at 5-15 min) stimulation of the MAPK catalytic activity
      in primary PBMC. Altogether, these findings suggest that HIV-1 Tat protein
      activates CREB in lymphoid cells through a signal cascade involving the MAPK
      pathway.

PMID- 9558096
TI  - Differentiation-specific, octamer-dependent costimulation of kappa transcription.
AB  - By mutational analysis of the octamer-TATA box intervening region in the mouse
      SP6 kappa promoter, we have mapped two octamer-dependent, costimulatory regions,
      A and B. The A region was active in late B cells only, while the B region was
      active throughout B cell differentiation. The B region was TATA proximal and
      contained a heptamer and an E box of the E2A type that is common in Vkappa
      promoters. Mutation of the heptamer element did not decrease transcriptional
      stimulation from this region, but mutations in, or immediately 5' of, the E box
      core sequence did. A protein binding to this region could be detected in nuclear
      extracts. The complex could only partially be competed with a muE5 binding site
      and could not be supershifted with Abs raised to E2A gene products, indicating
      that it may represent a novel E-box binding complex. The A region was located
      proximal to the octamer and contained a CCCT element that is conserved both with
      regard to position and sequence in human VkappaII promoters. By mutational
      analysis, the transcriptional stimulatory activity was mapped to the CCCT element
      that also is part of an early B cell factor (EBF) binding site. In late B cells,
      a novel protein (FA), which did not bind to the EBF binding site in the mb1
      promoter, interacted with the A region. This protein was found to be expressed at
      lower levels in early B cells as well as in HeLa cells. Thus, the octamer
      flanking sequence contains positive control elements that may act independently
      but that differ in the stage of B cell differentiation at which they are active.
      One of these factors is an example of an ubiquitously expressed transcription
      factor that participate in differentiation-specific transcriptional activation.

PMID- 9558097
TI  - IFN-gamma induction of the human monocyte chemoattractant protein (hMCP)-1 gene
      in astrocytoma cells: functional interaction between an IFN-gamma-activated site
      and a GC-rich element.
AB  - We characterized regulation of the human monocyte chemoattractant protein-1 (hMCP
      1) gene by IFN-gamma in astrocytoma cells, because astroglial cells express
      chemokines in several central nervous system inflammatory states. It was found
      that IFN-gamma-induced hMCP-1 transcription was rapid, transient, and mediated by
      a 213-bp promoter-proximal regulatory region of the gene. Our studies on both in
      vitro and in vivo states of the hMCP-1 regulatory region established requirement
      of an IFN-gamma-activated site (GAS) and the presence of IFN-gamma-inducible GAS
      binding activity involving at least STAT-1alpha for IFN-gamma-induced hMCP-1
      expression. Unexpectedly, in vivo genomic footprinting of the proximal regulatory
      region of the IFN-gamma-induced gene revealed protection of a GC-rich sequence
      (GC box) with the same temporal pattern as that seen at the GAS; in vitro, this
      GC-rich element is associated with nuclear factor Sp1. These observations
      suggested a cooperative interaction between the GAS and the GC box element.
      Interestingly, site-specific mutations that abolished GC-box or GAS-element
      function produced clearly disparate results. Disruption of the GC box did not
      affect fold induction by IFN-gamma but reduced promoter-reporter expression by
      half. Conversely, GAS mutation abrogated induction but did not affect the
      magnitude of expression. These results establish the importance of the GAS
      element for induction of hMCP-1 and further our understanding of IFN-gamma
      mediated transcriptional induction by providing the first evidence in vivo for
      inducible signaling to the GC box by this cytokine.

PMID- 9558098
TI  - Target recognition of beta2-glycoprotein I (beta2GPI)-dependent anticardiolipin
      antibodies: evidence for involvement of the fourth domain of beta2GPI in antibody
      binding.
AB  - Beta2-glycoprotein I (beta2GPI) is an absolute requirement for the binding of
      autoimmune anticardiolipin Abs (aCL) to cardiolipin (CL). We evaluated the target
      recognition of human beta2GPI by IgG derived from two patients with primary and
      two with secondary antiphospholipid syndrome. The total IgG serum fractions and
      beta2GPI affinity-purified IgGs were assessed by using various domain-deleted
      mutants (DM) of human beta2GPI (DMs: I-III, I-IV, II-V, III-V, IV-V, and V) and
      mouse mAbs against individual beta2GPI domains. The four IgGs bound slightly to
      CL in the absence of beta2GPI and showed increased binding in the beta2GPI
      presence. Following affinity purification of the IgGs on a beta2GPI column,
      reactivity toward CL was absent. DMs containing domain V inhibited the binding of
      biotinylated beta2GPI to CL. The addition to CL-coated plates of DM V, but not
      the other DMs, reduced the binding of all four IgGs. The anti-beta2GPI IgGs bound
      only to complete beta2GPI and DM I-IV coated on the plates. The binding to plate
      adsorbed beta2GPI could be inhibited by complete beta2GPI and DM I-IV, the latter
      being a more efficient inhibitor. Further, the human anti-beta2GPI IgGs could
      compete with the binding to beta2GPI of Cof-21 mouse mAb (directed at domain IV),
      but not with the two other mouse mAbs. The results suggest that some
      "autoimmune:" beta2GPI-dependent anticardiolipin Abs recognize a beta2GPI target
      that is distinct from the CL-binding site in domain V. The target site for some
      antiphospholipid syndrome IgGs appear to reside in domain IV of beta2GPI.

PMID- 9558099
TI  - Molecular cloning and functional characterization of the pig analogue of CD59:
      relevance to xenotransplantation.
AB  - In this work, we report the cloning of the cDNA for the porcine analogue of human
      CD59. Degenerate primers, derived from the N-terminal sequence of pig erythrocyte
      CD59, were used to obtain the corresponding cDNA sequence. From this sequence,
      gene-specific primers were designed and used to amplify the 3' and 5' ends of the
      cDNA using the rapid amplification of cDNA ends (RACE) method. The complete 768
      bp cDNA so obtained consisted of a 84-bp 5' untranslated region, a 26-amino-acid
      NH2-signal peptide, a 98-amino-acid coding region, including putative N
      glycosylation sites and a glycosylphosphatidylinositol-anchoring signal, and a
      312-bp 3' untranslated region. The mature protein sequence was 48% identical to
      human CD59 at the amino acid level. Northern blot analysis revealed several
      distinct CD59 transcripts, and a variability in expression levels of the
      different transcripts in the panel of tissues screened. Stable expression of pig
      CD59 in a CD59-negative human cell line conferred protection against lysis by
      complement from pig and several other species. Separate expression of pig and
      human CD59 at similar levels in the same cell line allowed a direct functional
      comparison between these two analogues. Pig CD59 and human CD59 showed similar
      activity in inhibiting lysis by complement from all species tested; in
      particular, expressed pig CD59 efficiently inhibited lysis by human complement.
      The relevance of these data to current work in the engineering of pig organs for
      xenotransplantation is discussed.

PMID- 9558100
TI  - Dendritic cells express multiple chemokine receptors used as coreceptors for HIV
      entry.
AB  - Cells of the dendritic lineage are thought to be among the first cells infected
      after mucosal exposure to HIV. In this study, we have identified the presence of
      multiple chemokine receptors on dendritic cells (DC) that may function as
      coreceptors for HIV entry. DC effectively used CCR5 for entry of macrophage (M)
      tropic isolates. CCR3, the eotaxin receptor, initially identified on eosinophils,
      is expressed on DC and may be used as an entry coreceptor by certain dual-tropic
      strains. CXCR4 was not expressed on DC, although SDF-1 induced a calcium flux and
      DC could be infected by T cell line (T)-tropic HIV. Our findings provide evidence
      for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T
      tropic strains of HIV. DC from individuals homozygous for a 32-bp deletion of the
      CCR5 gene are also infectable with M-tropic strains of HIV-1, and this infection
      is inhibited by stromal cell-derived factor (SDF)1, suggesting that this receptor
      can also be used by M-tropic HIV for entry. Delineation of the spectrum of
      coreceptor usage on DC may offer new approaches to interfere with the initiation
      and propagation of HIV infection.

PMID- 9558101
TI  - Lymphocytes produce IL-1beta in response to Fcgamma receptor cross-linking:
      effects on parenchymal cell IL-8 release.
AB  - Neutrophils mediate tissue injury in response to immune complexes, although the
      factors that induce their recruitment are incompletely understood. We have
      reported that lymphocytes may be important regulators of monocyte and macrophage
      IL-8 release in the presence of immobilized IgG. Since tissue parenchymal cells
      are important local producers of IL-8 but are not directly stimulated by FcgammaR
      cross-linking, we hypothesized that lymphocytes may also regulate parenchymal IL
      8 release. Supernatants from lymphocytes incubated on immobilized IgG induced
      primary human fibroblasts and human mesangial cells to produce IL-8 (17 +/- 3.5
      and 44 +/- 8 ng/ml, respectively). Fibroblast and mesangial cell IL-8 mRNA levels
      were similarly increased by the conditioned lymphocyte supernatant. Immobilized
      anti-human FcgammaRIII, but not FcgammaRI or FcgammaRII Abs, could stimulate this
      IL-8-inducing activity in lymphocytes, suggesting that FcgammaRIII-bearing
      lymphocytes were responsible. Supernatants from lymphocytes incubated on
      immobilized IgG contained 2.2 +/- 0.8 ng/ml of IL-1beta, while enriched monocyte
      preparations from the same donors incubated on immobilized IgG released only 0.1
      +/- 0.04 ng/ml of IL-1beta (p = 0.05). Consistent with the identification of IL
      1beta as the lymphocyte factor, fibroblast or mesangial cell IL-8 release induced
      by the IgG-stimulated lymphocyte supernatants was inhibited by 1) the combination
      of IL-1R antagonist and soluble type II IL-1R, 2) an IL-1-converting enzyme
      inhibitor, or 3) anti-IL-1beta but not preimmune Abs. These data suggest that
      targeted deposits of IgG can stimulate FcgammaRIII-bearing lymphocytes to produce
      IL-1beta, which induces parenchymal cell IL-8 release.

PMID- 9558102
TI  - Induction of a Th1 immune response and simultaneous lack of activation of a Th2
      response are required for generation of immunity to leishmaniasis.
AB  - Experimental systems based on immunization with plasmid DNA or immune-stimulating
      complexes were used to delineate the requirements for generation of protective
      immunity against murine leishmaniasis. Vaccination with plasmid DNA encoding the
      host-protective Leishmania major parasite surface Ag-2 primed for an essentially
      exclusive Th1 response that protected mice against L. major infection. In
      contrast, parasite surface Ag-2 in immune-stimulating complexes generated an
      immune response with mixed Th1-like and Th2-like properties that was not
      protective despite the activation of large numbers of CD4+ T cells secreting IFN
      gamma. These results indicate that a Th1 response is sufficient to protect
      against cutaneous leishmaniasis, but the induction of a simultaneous Th2 response
      abrogates the Th1 effector function. DNA vaccines may therefore have an advantage
      for diseases in which protection depends on the induction of Th1 responses.

PMID- 9558103
TI  - Mice lacking IL-12 develop polarized Th1 cells during viral infection.
AB  - Studies in IL-12-deficient mice established the necessity for IL-12 to generate a
      Th1 cytokine response that is often required for elimination of intracellular
      pathogens. In this study, we demonstrate that mice with a targeted disruption of
      the IL-12p40 and/or p35 gene effectively control liver damage induced by mouse
      hepatitis virus (MHV) infection, similar to wild-type animals. In contrast, MHV
      infected IFN-gamma receptor-deficient (IFN-gammaR[-/-]) mice showed an increased
      susceptibility to coronaviral hepatitis. Surprisingly, MHV-infected mice lacking
      IL-12 produced a polarized Th1-type cytokine response, as evidenced by high IFN
      gamma and nondetectable IL-4 production by CD4+ splenocytes and normal virus
      specific serum IgG2a/IgG1 ratios. The virus-induced type 1 cytokine secretion
      pattern was not reversed in IL-12-deficient mice by in vivo neutralization of IFN
      gamma nor in IFN-gammaR(-/-) mice receiving IL-12-neutralizing Abs. In IL-12
      deficient mice, Th1-type responses were also generated upon immunization with
      inactivated MHV. In contrast, following immunization with keyhole limpet
      hemocyanin, mice lacking IL-12 mounted strongly reduced specific IgG2a and
      increased IgE responses, indicative of a type 2-dominated cytokine pattern. These
      findings demonstrate that following a virus infection, IL-12 is not essential for
      the generation of polarized T cell type 1 cytokine expression and associated
      immune responses, which is in marked contrast to nonviral systems. Our data
      suggest that viruses may selectively induce IFN-gamma production and Th1-type
      immune reactions even in the absence of IL-12.

PMID- 9558104
TI  - Immunopathology of herpetic stromal keratitis: discordance in CD4+ T cell
      function between euthymic host and reconstituted SCID recipients.
AB  - Infection of the mouse cornea with herpes simplex virus (HSV) results in an
      immunopathologic disease of the eye termed herpetic stromal keratitis (HSK), in
      which the principal orchestrator is the CD4+ T cell. The mouse genotype largely
      determines susceptibility or resistance to HSK. BALB/c mice (H2dIgh-1a) are
      susceptible, while its congenic C.B-17 strain (H2dIgh-1b), which differs only in
      the Ig heavy chain locus, is resistant to HSK. As the magnitude and duration of
      viral replication as well as anti-HSV immune responses were similar in both
      strains, it was determined whether resistance was due to failure of CD4+ T cells
      to organize the immunopathologic reaction. Adoptive transfer of HSV-primed or
      naive CD4+ T cells from resistant C.B-17 strain into HSV-infected SCID mice
      resulted in HSK lesions indistinguishable from those caused by similar transfers
      of BALB/c CD4+ T cells. Similar results were obtained with transfers of whole T
      cell populations as well as with unfractionated splenocytes from the resistant
      mice. These results show that while intact C.B-17 mice exhibit resistance to HSK,
      they possess potentially pathogenic CD4+ T cells in their repertoire. The data
      suggest that the HSV-infected SCID mouse provides a proinflammatory
      microenvironment that overrides regulatory controls and/or cause activation of
      quiescent cells into aggressive effector T cells that orchestrate HSK.

PMID- 9558105
TI  - Effect of antigen-processing efficiency on in vivo T cell response magnitudes.
AB  - T lymphocytes eradicate and provide long-term immunity to infections caused by
      intracellular pathogens. The mechanisms that determine in vivo T cell response
      sizes are poorly understood. Although it is speculated that the relative
      processing efficiency of different epitopes determines the hierarchy of T cell
      responses following immunization, this hypothesis has not been rigorously tested.
      We therefore mutagenized the secreted p60 Ag of Listeria monocytogenes to alter
      the efficiency of T cell epitope generation. Ag-processing efficiencies in cells
      infected with the different L. monocytogenes mutants ranged from one H2-Kd
      associated p60 217-225 epitope generated per 15 intracellularly degraded p60
      molecules (1/15) to one epitope per 350 degraded p60 molecules (1/350), i.e., a
      spectrum encompassing a 20-fold range of efficiencies. Mice infected with L.
      monocytogenes secreting inefficiently processed p60 (1/350) did not mount p60 217
      225-specific T cell responses. However, increasing the efficiency of Ag
      processing by a factor of 5 to 1/70 restored the T cell response size to normal,
      while further increases in the efficiency of p60 217-225 generation to 1/50,
      1/35, and 1/17 did not further augment specific T cell responses. Our studies
      demonstrate an Ag-processing threshold for in vivo T cell activation.
      Surprisingly, once this threshold is achieved, further enhancement of Ag
      processing efficiency does not enhance the size of T cell responses.

PMID- 9558107
TI  - Intraepithelial infiltration by mast cells with both connective tissue-type and
      mucosal-type characteristics in gut, trachea, and kidneys of IL-9 transgenic
      mice.
AB  - IL-9 transgenic mice were analyzed for the presence of mast cells in different
      tissues. In these mice, increased mast cell infiltration was found in the gastric
      and intestinal epithelium as well as in the upper airways and kidney epithelium,
      but not in other organs, such as skin. IL-9 transgenic mast cells do not show
      signs of massive degranulation such as that found in IL-4 transgenic mice and are
      not involved in spontaneous pathologic changes. Gastric mast cells showed a
      phenotype related to connective-type mast cells, since they were stained by
      safranin, and strong expression of mouse mast cell protease-4 and -5 was found in
      this organ. However, they also expressed proteases related to the mucosal cell
      type, such as mouse mast cell protease-1 and -2. In vitro, although IL-9 by
      itself did not induce mast cell development from bone marrow progenitors, it
      strongly synergized with stem cell factor for the growth and differentiation of
      mast cells expressing the same protease pattern as that observed in IL-9
      transgenic mice. Since constitutive stem cell factor expression was observed in
      vivo, and anti-c-Kit Abs inhibited IL-9 transgenic mastocytosis in the gut, this
      synergistic combination of factors is likely to be responsible for the
      mastocytosis observed in IL-9 transgenic mice. Taken together, these data
      demonstrate that IL-9 induces the in vivo amplification of a nonclassical mast
      cell subset with a mucosal localization but expressing proteases characteristic
      of both connective tissue-type and mucosal mast cells.

PMID- 9558106
TI  - Vascular adhesion protein-1 and ICAM-1 support the adhesion of tumor-infiltrating
      lymphocytes to tumor endothelium in human hepatocellular carcinoma.
AB  - T cell-mediated mechanisms are important in the defense against solid organ
      tumors. Why some tumors are more heavily infiltrated by T cells than others is
      poorly understood but is likely to depend upon adhesive interactions between
      circulating lymphocytes and tumor endothelium. In support of this hypothesis, the
      present study shows that primary human hepatocellular carcinomas (HCC) are more
      heavily infiltrated with T cells than colorectal hepatic metastases (CHM), and
      that their tumor vessels express high levels of several adhesion molecules. In
      HCC, an intense T cell infiltrate is observed within the tumor associated with
      strong expression of ICAM-1 and vascular adhesion protein-1 (VAP-1) on tumor
      endothelium. In contrast, fewer T cells infiltrated CHM and these tumors have
      little ICAM-1 and no detectable VAP-1 or VCAM-1 on tumor endothelium. T cells
      infiltrating both tumors are LFA-1 and very late Ag (VLA)-4 high. In vitro tissue
      binding studies demonstrated that T cells bound readily to tumor endothelium in
      HCC, and Abs to ICAM-1, VAP-1, and to a lesser extent VCAM-1 could inhibit this
      binding. VAP-1 supported sialic acid-dependent adhesion under shear stress,
      suggesting that VAP-1 and ICAM-1 mediate, respectively, tethering and firm
      adhesion. In contrast, very few T cells bound to tumor vessels in CHM. Thus our
      data suggest that the VAP-1/VAP-1 receptor and ICAM-1/LFA-1 pathways are
      important in the recruitment of T cells to HCC. The strong expression of VAP-1 on
      tumor endothelium distinguishes HCC from CHM and supports our previous hypothesis
      that VAP-1 is an important hepatic endothelial adhesion molecule.

PMID- 9558108
TI  - Preprosomatostatin messenger RNA is expressed by inflammatory cells and induced
      by inflammatory mediators and cytokines.
AB  - Somatostatin (SOM) is a 14-amino acid cyclic peptide that regulates granulomatous
      inflammation. SOM inhibits the release of IFN-gamma from murine granuloma T cells
      that express SOM receptors. SOM is synthesized as preprosomatostatin (ppSOM), a
      precursor peptide that is cleaved to release active SOM. In this paper, we
      demonstrate that granuloma cells express mRNA for this important immunoregulator,
      and that inflammatory mediators rapidly induce ppSOM mRNA in the splenocytes of
      uninfected, normal (NL) mice. We developed a sensitive, quantitative PCR assay
      that measures ppSOM mRNA down to 100 transcripts per microg of total RNA.
      Dispersed granuloma cells expressed authentic ppSOM mRNA as determined by RT-PCR
      and cDNA sequencing. The PCR assay readily detected ppSOM mRNA in splenocytes
      isolated from schistosome-infected mice, but not in splenocytes from NL mice.
      Splenic ppSOM mRNA expression correlated with the onset of parasite egg
      deposition and granuloma formation. A 4-h in vitro stimulation with LPS, rIL-10,
      rIFN-gamma, rTNF-alpha, prostaglandin E2, or dibutyryl cAMP induced ppSOM mRNA in
      NL splenocytes that otherwise lacked this transcript. Splenocytes from severe
      combined immunodeficient or recombination activating gene 1-deficient mice
      expressed ppSOM after exposure to rIL-10, suggesting that neither T nor B cells
      are necessary for ppSOM mRNA induction. A survey of cell lines demonstrated
      expression of ppSOM mRNA by P388D1 and J774A.1 macrophage-like cells. These data
      suggest that SOM, which is probably derived from macrophages, is an inducible
      component of the innate immune system that regulates T cell IFN-gamma production.

PMID- 9558109
TI  - An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of
      the IL-4/IL-13 receptor system completely abrogates humoral immune response to
      allergen and development of allergic symptoms in vivo.
AB  - We have analyzed in vivo effects of the murine IL-4 mutant Q116D/Y119D (QY),
      which forms unproductive complexes with IL-4Ralpha and is an antagonist for IL-4
      and IL-13 in vitro. Treatment of BALB/c mice with QY during immunization with OVA
      completely inhibited synthesis of OVA-specific IgE and IgG1. BALB/c-derived
      knockout mice lacking either IL-4 or IL-4Ralpha also did not develop specific IgE
      or IgG1, but mounted a much stronger IgG2a and IgG2b response than wild-type
      mice. In contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a,
      IgG2b, and IgG3 synthesis, which may indicate the development of tolerance toward
      the allergen. Associated with the lack of IgE synthesis in QY-treated wild-type
      mice and in IL-4(-/-) mice used as a control was the failure to develop immediate
      cutaneous hypersensitivity or anaphylactic shock upon rechallenge. Interestingly,
      QY treatment also inhibited humoral immune responses and allergic reactivity in
      SJL/J mice, a strain that did not produce IgE, but displayed IgE-independent mast
      cell degranulation mediated by specific IgG1. We conclude that QY inhibits Ag
      specific humoral immune responses and allergic symptoms mediated either by IgE or
      IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a, IgG2b, and
      IgG3, but the induction of tolerance toward nonhazardous protein Ags should be
      advantageous for therapy of atopic disorders and other Th2-dominated diseases.

PMID- 9558110
TI  - Lidocaine and its analogues inhibit IL-5-mediated survival and activation of
      human eosinophils.
AB  - Eosinophils and cytokines active on eosinophils, especially IL-5, are believed to
      be critically involved in chronic allergic diseases. IL-5 activates eosinophils
      and enhances their survival in vitro by delaying apoptosis. In this study, we
      found that lidocaine and six analogues blunt responses of eosinophils to IL-5.
      Lidocaine and its derivatives inhibit IL-5-mediated eosinophil survival in a
      concentration-dependent manner (IC50 = 110 microM for 30 pg/ml IL-5). At
      suboptimal lidocaine concentrations, the eosinophil survival response to IL-5
      shifts and more IL-5 is required to maintain survival. The inhibitory effect
      requires at least 24-h exposure of eosinophils to lidocaine, and the protein
      kinase C activator, PMA, completely reverses the inhibition. A multiparameter
      flow-cytometric analysis shows that lidocaine hastens the apoptosis of
      eosinophils normally delayed by IL-5. Lidocaine does not affect IL-5R expression
      or IL-5-induced protein tyrosine phosphorylation. Lidocaine also inhibits
      eosinophil survival mediated by IL-3 or granulocyte-macrophage CSF, although less
      potently than that mediated by IL-5. Furthermore, lidocaine inhibits eosinophil
      superoxide production stimulated by IL-5, granulocyte-macrophage CSF, or IL-3,
      but not that stimulated by platelet-activating factor, immobilized IgG, or PMA.
      Lidocaine and its derivatives show novel immunomodulatory properties and are able
      to blunt eosinophil responses to cytokines in addition to their local anesthetic
      or antiarrhythmic properties. Thus, lidocaine and its derivatives may represent a
      new class of therapeutic agents to treat patients with allergic diseases.

PMID- 9558111
TI  - Impaired macrophage function and enhanced T cell-dependent immune response in
      mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor.
AB  - The CC-chemokine receptor CCR5 has been shown to be the major coreceptor for HIV
      1 entry into cells, and humans with homozygous mutation in the ccr5 gene are
      highly resistant to HIV-1 infection, despite the existence of many other HIV-1
      coreceptors. To investigate the physiologic function of CCR5 and to understand
      the cellular mechanisms of these clinical observations, we generated a CCR5
      deficient mouse model (ccr5[-/-]) by targeted deletion of the ccr5 gene. We found
      that although developed normally in a pathogen-free environment, CCR5-deficient
      mice showed reduced efficiency in clearance of Listeria infection and exert a
      protective effect against LPS-induced endotoxemia, reflecting a partial defect in
      macrophage function. In addition, CCR5-deficient mice had an enhanced delayed
      type hypersensitivity reaction and increased humoral responses to T cell
      dependent antigenic challenge, indicating a novel role of CCR5 in down-modulating
      T cell-dependent immune response.

PMID- 9558112
TI  - Induction and enhancement of Fc(epsilon)RI-dependent mast cell degranulation
      following coculture with activated T cells: dependency on ICAM-1- and leukocyte
      function-associated antigen (LFA)-1-mediated heterotypic aggregation.
AB  - Activated mast cells are known to reside in close apposition to T cells in
      various inflammatory processes. In this regard, we have reported that activated
      mast cells form heterotypic aggregates with activated lymphocytes. To determine
      whether this interaction would result in mast cell degranulation, we examined the
      effect of EL-4, 2B4, or freshly isolated T cells, activated by PMA or immobilized
      anti-CD3 mAb, on histamine release from murine bone marrow-derived cultured mast
      cells (BMCMC). Coculturing BMCMC with activated but not with resting T cells
      resulted in significant histamine release. Also, Fc(epsilon)RI cross-linking
      induced degranulation was augmented when BMCMC were cocultured with activated T
      cells. Supernatants of activated T cells failed to exert the stimulatory effect.
      Separation of the two cell populations with a porous membrane prevented
      degranulation, indicating that BMCMC activation was adhesion dependent. Indeed,
      the kinetics of histamine release paralleled the kinetics of the formation of
      heterotypic aggregates, which peaked after 12 h of coculture. Introduction of
      anti-LFA-1 and anti-intercellular adhesion molecule-1 mAb inhibited the adhesion
      induced mast cell degranulation. These data suggest a heretofore unrecognized
      mast cell activation pathway induced by LFA-1/intercellular adhesion molecule-1
      mediated heterotypic aggregation with activated T cells.

PMID- 9558113
TI  - Posttranslational modifications affect the activity of the human monocyte
      chemotactic proteins MCP-1 and MCP-2: identification of MCP-2(6-76) as a natural
      chemokine inhibitor.
AB  - Chemokines are important mediators in infection and inflammation. The monocyte
      chemotactic proteins (MCPs) form a subclass of structurally related C-C
      chemokines. MCPs select specific target cells due to binding to a distinct set of
      chemokine receptors. Recombinant and synthetic MCP-1 variants have been shown to
      function as chemokine antagonists. In this study, posttranslationally modified
      immunoreactive MCP-1 and MCP-2 were isolated from mononuclear cells. Natural
      forms of MCP-1 and MCP-2 were biochemically identified by Edman degradation and
      mass spectrometry and functionally characterized in chemotaxis and Ca2+
      mobilization assays. Glycosylated MCP-1 (12 and 13.5 kDa) was found to be two- to
      threefold less chemotactic for monocytes and THP-1 cells than nonglycosylated MCP
      1 (10 kDa). Natural, NH2-terminally truncated MCP-1(5-76) and MCP-1(6-76) were
      practically devoid of bioactivity, whereas COOH-terminally processed MCP-1(1-69)
      fully retained its chemotactic and Ca2+-inducing capacity. The capability of
      naturally modified MCP-1 forms to desensitize the Ca2+ response induced by intact
      MCP-1 in THP-1 cells correlated with their agonistic potency. In contrast,
      naturally modified MCP-2(6-76) was devoid of activity, but could completely block
      the chemotactic effect of intact MCP-2 as well as that of MCP-1, MCP-3, and
      RANTES. Carboxyl-terminally processed MCP-2(1-74) did retain its chemotactic
      potency. Although comparable as a chemoattractant, natural intact MCP-2 was found
      to be 10-fold less potent than MCP-1 in inducing an intracellular Ca2+ increase.
      It can be concluded that under physiologic or pathologic conditions,
      posttranslational modification affects chemokine potency and that natural MCP-2(6
      76) is a functional C-C chemokine inhibitor that might be useful as an inhibitor
      of inflammation.

PMID- 9558114
TI  - Hydrogen peroxide induces up-regulation of Fas in human endothelial cells.
AB  - Hydrogen peroxide (H2O2), an oxidant generated by inflammatory cells, is an
      important mediator of injury of endothelial cells (ECs). Here we show that H2O2
      induces up-regulation of the expression of Fas, a death signal, in human ECs in
      culture. Flow cytometric analysis with a mAb against human Fas showed that
      incubation for 24 h with H2O2 induced a dose-dependent increase in the level of
      Fas in ECs. Coincubation with catalase, which rapidly degrades H2O2, inhibited
      H2O2-induced up-regulation of Fas. H2O2 also induced a dose-dependent increase in
      Fas mRNA level. A significant increase in Fas mRNA levels was observed from 6 h
      after stimulation with H2O2. Vanadate, a protein phosphatase inhibitor,
      significantly enhanced Fas mRNA and protein levels in H2O2-treated ECs. On the
      other hand, genistein, a tyrosine kinase inhibitor, inhibited H2O2-induced Fas
      mRNA expression. Furthermore, a flow cytometric method with propidium iodide
      staining and electron microscopic analysis showed that incubation with an
      agonistic Ab against Fas (anti-Fas IgM) induced apoptosis in H2O2-treated cells.
      These findings suggest that H2O2 induces up-regulation of Fas in ECs and that
      activation of protein tyrosine kinase may be involved in the mechanism of H2O2
      induced Fas expression. Therefore, Fas-mediated apoptosis may have a pathologic
      role in H2O2-induced EC injury and thereby provide a new therapeutic target.

PMID- 9558115
TI  - Involvement of the IL-2 receptor gamma-chain (gammac) in the control by IL-4 of
      human monocyte and macrophage proinflammatory mediator production.
AB  - IL-4 has potent anti-inflammatory properties on monocytes and suppresses both IL
      1beta and TNF-alpha production. Well-characterized components of the IL-4
      receptor on monocytes include the 140-kDa alpha-chain and the IL-2R gamma-chain,
      gammac, which normally dimerize 1:1 for signaling from the receptor. However,
      mRNA levels for gammac were very low in 7-day-cultured monocytes. As mRNA levels
      for gammac declined with culture, so too did the ability of IL-4 to down-regulate
      LPS-induced TNF-alpha production. In contrast, IL-4 consistently down-regulated
      IL-1beta production by cultured monocytes. Immunoprecipitation and Western blot
      analyses demonstrated that 7-day-cultured monocytes do not express the
      functionally active 64-kDa gammac protein. This was associated with decreased
      STAT6 activation by IL-4. Studies with Abs to gammac and an IL-4 mutant that is
      unable to bind to gammac showed that IL-4 can suppress IL-1beta but not TNF-alpha
      production by LPS-stimulated monocytes in the presence of little or no
      functioning gammac. IL-4 also suppressed IL-1beta but not TNF-alpha production by
      Mono Mac 6 cells, which express minimal levels of gammac. For gammac-expressing
      LPS/PMA-activated U937 cells, IL-4 decreased both TNF-alpha and IL-1beta
      production. These results suggest that functional gammac is not present on in
      vitro-derived macrophages, and that while some anti-inflammatory responses to IL
      4 are lost with this down-regulation of functional gammac, others are retained.
      We conclude that different functional responses to IL-4 by human monocytes and
      macrophages are regulated by different IL-4 receptor configurations.

PMID- 9558116
TI  - Human polymorphonuclear leukocytes adhere to complement factor H through an
      interaction that involves alphaMbeta2 (CD11b/CD18).
AB  - The work presented here demonstrates that human complement factor H is an
      adhesion ligand for human neutrophils but not for eosinophils. The adherence of
      polymorphonuclear leukocytes (PMNs) to plastic wells coated with factor H
      depended on divalent metal ions and was augmented by C5a and TNF-alpha. PMN
      adhesion to factor H in the presence or absence of C5a was blocked specifically
      by mAbs against CD11b or CD18. Affinity purification using factor H Sepharose
      followed by immunoprecipitation using mAbs to various integrin chains identified
      Mac-1 (CD11b/CD18) as a factor H binding receptor. The presence of surface bound
      factor H enhanced neutrophil activation resulting in a two- to fivefold increase
      in the generation of hydrogen peroxide by PMNs stimulated by C5a or TNF-alpha.
      When factor H was mixed with PMNs, 1.4 to 3.8-fold more cells adhered to
      immobilized heparin or chondroitin A. In addition, augmented adhesion of PMNs was
      measured when factor H, but not HSA or C9, was absorbed to wells that were first
      coated with heparin or chondroitin A. The adhesion of PMNs to glycosaminoglycan
      factor H was blocked by mAbs to CD11b and CD18. These studies demonstrate that
      factor H is an adhesion molecule for human neutrophils and suggest that the
      interaction of factor H with glycosaminoglycans may facilitate the tethering of
      this protein in tissues allowing factor H to serve as a neutrophil adhesion
      ligand in vivo.

PMID- 9558117
TI  - Regulation of E-cadherin-mediated adhesion in Langerhans cell-like dendritic
      cells by inflammatory mediators that mobilize Langerhans cells in vivo.
AB  - Adhesion of Langerhans cells (LC) to keratinocytes is mediated by E-cadherin. IL
      1, TNF-alpha, and LPS mobilize LC from epidermis and presumably attenuate LC
      keratinocyte adhesion. To determine whether these mediators modulated LC E
      cadherin-dependent adhesion directly, we characterized their effects on LC-like
      dendritic cells expanded from murine fetal skin (FSDDC). FSDDC were propagated
      from day 16 C57BL/6 fetal skin and isolated as aggregates (FSDDC-A) in which
      homophilic adhesion was mediated by E-cadherin. IL-1, TNF-alpha, and LPS induced
      dissociation of FSDDC-A that began within 4 to 8 h and was complete within 20 h.
      Anti-IL-1RI mAb inhibited disaggregation caused by IL-1alpha and IL-1beta, but
      not that induced by TNF-alpha or LPS. Anti-TNF-alpha mAb inhibited the effect of
      TNF-alpha and LPS, but not that caused by IL-1alpha or IL-1beta. Flow cytometry
      of FSDDC-A revealed that IL-1, TNF-alpha, and LPS induced increased expression of
      MHC class II, CD40, and CD86 and decreased E-cadherin expression that was
      temporally related to dissociation of aggregates. IL-1 and TNF-alpha caused a
      rapid reduction in FSDDC E-cadherin mRNA levels that preceded the decrease in E
      cadherin surface expression. These results demonstrate that cytokines that induce
      LC emigration in vivo act directly on LC-like cells in vitro, reduce E-cadherin
      mRNA levels, down-regulate E-cadherin surface expression, and induce a loss of E
      cadherin-mediated adhesion.

PMID- 9558118
TI  - IFN-gamma limits macrophage expansion in MRL-Fas(lpr) autoimmune interstitial
      nephritis: a negative regulatory pathway.
AB  - IFN-gamma is capable of enhancing and limiting inflammation. Therefore, an
      increase in IFN-gamma in autoimmune MRL-Fas(lpr) mice could exacerbate or thwart
      renal injury. We have established a retroviral gene transfer approach to incite
      interstitial nephritis in MRL-Fas(lpr) mice that is rapid, enduring, and
      circumscribed. Renal tubular epithelial cells (TEC) were genetically modified to
      secrete macrophage (Mphi) growth factors (CSF-1-TEC, GM-CSF-1-TEC) and infused
      under the renal capsule. To determine the impact of IFN-gamma in Mphi growth
      factor-incited renal injury, we constructed a MRL-Fas(lpr) IFN-gamma-receptor
      (IFN-gammaR)-deficient strain. Gene transfer of CSF-1 or GM-CSF incited more
      severe interstitial nephritis in IFN-gammaR-deficient than in IFN-gammaR-intact
      MRL-Fas(lpr) mice, consisting of an increase of Mphi. To determine the mechanism
      responsible for the increase in Mphi in IFN-gammaR-deficient MRL-Fas(lpr) mice,
      we evaluated Mphi proliferation, apoptosis, and recruitment. Proliferation of
      bone marrow Mphi from IFN-gammaR-intact MRL-Fas(lpr) costimulated with CSF-1 or
      GM-CSF and IFN-gamma was reduced twofold, while the IFN-gammaR-deficient MRL
      Fas(lpr) bone marrow Mphi remained stable. Furthermore, we detected more
      proliferating and fewer apoptotic Mphi within the interstitium in IFN-gammaR
      deficient MRL-Fas(lpr) mice. Using unilateral ureteral ligation we established
      that IFN-gammaR signaling does not alter Mphi recruitment into the kidney. Thus,
      the increase in Mphi elicited by Mphi growth factors in IFN-gammaR-deficient MRL
      Fas(lpr) mice is a result of enhanced proliferation and decreased apoptosis, and
      is independent of recruitment. Taken together, we suggest that IFN-gamma provides
      a negative regulatory pathway capable of limiting Mphi-mediated renal
      inflammation.

PMID- 9558119
TI  - Disparate roles for TNF-alpha and Fas ligand in concanavalin A-induced hepatitis.
AB  - Apoptosis is a physiologic process that serves to eliminate cells during
      development or in response to immunologic regulation. In acute inflammation,
      however, apoptosis triggered by the overproduction of "death factors" such as TNF
      alpha or Fas ligand (FasL) may contribute to tissue injury. Both TNF-alpha and
      FasL are presumed to convey an apoptotic signal by activating a cascade of
      cysteine-aspartate proteases, which includes IL-1beta-converting enzyme or
      caspase-1. In the present study, we evaluated the contribution of TNF-alpha and
      FasL, as well as the role of caspase-1, in Con A-induced hepatitis. We report
      here that TNF-alpha and FasL mRNA and protein levels are both increased in the
      livers of Con A-challenged mice. Using a novel inhibitor of TNF-alpha, we can
      confirm that Con A-induced hepatitis is primarily TNF-alpha dependent. Blockade
      of FasL with a soluble Fas immunoadhesin does not prevent liver injury in animals
      treated with Con A alone. However, administration of a matrix metalloproteinase
      inhibitor exacerbates liver injury, in part through a FasL-dependent process,
      since pretreatment with the soluble Fas immunoadhesin reduces liver injury in
      this model. In addition, mice lacking functional caspase-1 are resistant to Con A
      induced hepatitis, even after pretreatment with a matrix metalloproteinase
      inhibitor. We conclude that TNF-alpha plays a predominant role in Con A-induced
      liver injury, although concomitant activation of FasL can also lead to apoptotic
      injury. Furthermore, Con A-induced hepatitis is caspase-1 dependent.

PMID- 9558120
TI  - Dendritic cells are required for the development of chronic eosinophilic airway
      inflammation in response to inhaled antigen in sensitized mice.
AB  - Asthma is characterized by chronic eosinophilic inflammation of the airways, and
      allergen-specific Th2 lymphocytes are thought to play a major role in the
      development and maintenance of this type of inflammation in allergic asthma. It
      is generally accepted that airway dendritic cells (DC) are essential for
      stimulating naive T cells in a primary immune response to inhaled Ag and for the
      development of allergic sensitization. We have examined the role of airway DC in
      stimulating memory T cells in a secondary response to inhaled Ag and the
      subsequent development of chronic airway inflammation. In our mouse model of
      asthma, OVA aerosol challenge in OVA-sensitized mice leads to CD4-dependent
      peribronchial and perivascular eosinophilic inflammation, lung Th2 cytokine
      production, and systemic IgE production. We have used conditional depletion of
      airway DC by treatment of thymidine kinase-transgenic mice with the antiviral
      drug ganciclovir to deplete DC during the secondary exposure to OVA. In
      sensitized thymidine kinase-transgenic mice, a significant decrease in the number
      of bronchoalveolar CD4 and CD8 T lymphocytes and B lymphocytes was seen after
      ganciclovir treatment. In addition, Th2 cytokine-associated eosinophilic airway
      inflammation was almost completely suppressed. These studies demonstrate for the
      first time that the DC is essential for presenting inhaled Ag to previously
      primed Th2 cells in the lung, leading to chronic eosinophilic airway
      inflammation. Altering the function of airway DC may therefore be an important
      target for new anti-asthma therapy.

PMID- 9558121
TI  - A p55 TNF receptor immunoadhesin prevents T cell-mediated intestinal injury by
      inhibiting matrix metalloproteinase production.
AB  - Anti-TNF-alpha Ab therapy has been shown to be of benefit in the treatment of
      active Crohn's disease, but the tissue-injuring processes in the gut mediated by
      TNF-alpha that might be inhibited by neutralizing Ab are unknown. In this work,
      we have used a p55 TNF receptor-human IgG fusion protein (TNFR-IgG) to prevent
      the severe mucosal injury that ensues when lamina propria T cells in explant
      cultures of human fetal small intestine are directly activated with the lectin
      PWM. Following T cell activation and associated with mucosal injury, there is a
      marked elevation of soluble TNF-alpha in organ culture supernatants and a large
      increase in TNF-alpha mRNA transcripts. The addition of TNFR-IgG at the onset of
      cultures greatly reduced PWM-induced tissue injury, without inhibiting the
      increase in TNF-alpha and IFN-gamma transcripts seen following T cell activation.
      Mucosal injury in this model is mediated by endogenously-produced matrix
      metalloproteinases (MMPs). When TNFR-IgG was added to PWM-stimulated explants,
      there was a reduction in MMPs in the explant culture supernatants, especially
      stromelysin-1. Recombinant TNF-alpha and IL-1beta added directly to mucosal
      mesenchymal cell lines also caused an increase in MMP production, but only the
      former was inhibited by the TNFR-IgG. These results suggest that one of the ways
      in which TNF-alpha causes tissue injury in the gut is by stimulating mucosal
      mesenchymal cell to secrete matrix-degrading metalloproteinases. Neutralization
      of this activity should help maintain tissue integrity.

PMID- 9558122
TI  - Flt-3 ligand increases microchimerism but can prevent the therapeutic effect of
      donor bone marrow in transiently immunosuppressed cardiac allograft recipients.
AB  - C3H (H2k) mice received 50 x 10(6) B10 (H2b) bone marrow (BM) cells either alone
      or with flt-3 ligand (FL) (10 microg/day), tacrolimus (2 mg/kg/day), or both
      agents for 7 days. Donor MHC class II+ (IAb+) cells were quantitated in spleens
      by immunohistochemical analysis, and donor class II DNA detected in BM by PCR.
      Donor cells were rare in the BM alone and BM + FL groups, whereas there was a
      substantial increase in chimerism in the BM + tacrolimus group. Addition of FL to
      BM + tacrolimus led to a further eightfold increase in donor cells and enhanced
      donor DNA compared with the BM + tacrolimus group. This increase in donor cells
      was almost 500-fold compared with BM alone. C3H recipients of B10 heart
      allografts given perioperative B10 BM and tacrolimus (days 0-13) exhibited a
      markedly extended median graft survival time (MST, 42 days) compared with those
      given tacrolimus alone (MST, 22 days). Addition of FL (10 microg/day; 7 days) to
      BM + tacrolimus prevented the beneficial effect of donor BM (MST, 18 days). BM
      alone or BM + FL resulted in uniform early heart graft failure (MST < 8 days).
      Functional studies revealed maximal antidonor MLR and CTL activities in the BM-
      and BM + FL-treated groups, with minimal activity in the tacrolimus-treated
      groups. Thus, dramatic growth factor-induced increases in chimerism achieved
      under cover of immunosuppression may result in augmented antidonor T cell
      reactivity and reduced graft survival after immunosuppressive drug withdrawal.
      With FL, this may reflect striking augmentation of immunostimulatory dendritic
      cells.

PMID- 9558123
TI  - Complement-fixing elicited antibodies are a major component in the pathogenesis
      of xenograft rejection.
AB  - Hamster to rat cardiac xenografts undergo delayed rejection as compared with the
      hyperacute rejection of discordant xenografts. Elicited xenoreactive Abs (EXA)
      are thought to initiate hamster to rat cardiac xenograft rejection. In this
      study, we demonstrate that following transplantation of a hamster heart, rats
      generated high levels of EXA. Adoptive transfer into naive recipients of purified
      IgM, IgG2b, or IgG2c, but not IgG1 or IgG2a EXA, induced xenograft rejection in a
      complement-dependent manner. Ability of EXA to cause rejection correlated with
      complement activation, platelet aggregation, and P-selectin expression in the
      xenograft endothelium. Cyclosporin A (CyA) administration, after transplantation,
      totally suppressed IgG1, IgG2a, IgG2b, and IgG2c EXA, and inhibited IgM EXA
      production, but failed to overcome rejection. Administration of cobra venom
      factor (CVF), 1 day before and at the time of transplantation, resulted in
      complement inhibition during 3 days after transplantation, which failed to
      overcome rejection. Combination of CyA and CVF, which we have previously shown to
      overcome rejection, resulted in suppression of IgG EXA production and in the
      return of IgM XNA to preimmunization serum levels, 3 to 7 days after
      xenotransplantation, while complement remained inhibited. Thus, under CyA/CVF
      treatment, complement activation by hamster cells was suppressed following
      xenotransplantation, and presumably for this reason xenograft rejection did not
      occur. In conclusion, our data demonstrate that EXA play a pivotal role in the
      pathogenesis of xenograft rejection and that CyA and CVF suppress xenograft
      rejection by preventing exposure of xenograft endothelial cells to complement
      activation by EXA.

PMID- 9558124
TI  - Requirement for in vivo production of IL-4, but not IL-10, in the induction of
      proliferative suppression by filarial parasites.
AB  - Loss of T lymphocyte proliferation and the emergence of a host response that is
      dominated by a Th2-type profile are well-established features of human
      filariasis. We have previously reported that adherent peritoneal exudate cells
      (PEC) from mice transplanted with adult Brugia malayi parasites suppress the
      proliferation of lymphocytes without blocking Ag-cytokine production in vitro. We
      now show that infection of mice with the infective larval (L3) stage of B. malayi
      generates a similar population of PEC. Suppressive cells are generated within 7
      days of infection and mediate their effects through a nitric oxide-independent
      pathway. Both L3 and adult infection elicit high levels of host IL-4 whereas the
      microfilarial stage of the parasite induces IFN-gamma production and does not
      generate a similar form of suppression. Production of host IL-4 was necessary to
      allow the generation of suppressive PEC, given that IL-4-deficient mice implanted
      with adult parasites failed to induce proliferative block. However, IL-10
      deficient mice implanted with adult parasites resulted in T cell suppression,
      indicating that IL-10 is not essential for the induction of hyporesponsiveness.
      Neither IL-4 nor IL-10 were directly responsible for ablating cellular
      proliferation in vitro, as the addition of neutralizing Ab to either cytokine did
      not reverse the proliferative block. Thus, IL-4 produced in vivo in response to
      filarial L3 and adult parasites is essential for the induction of proliferative
      suppression but is not itself the suppressive factor.

PMID- 9558125
TI  - Relative tissue distributions of cyclosporine and sirolimus after concomitant
      peroral administration to the rat: evidence for pharmacokinetic interactions.
AB  - The authors sought to determine the effect of concomitant peroral (PO)
      administration of cyclosporine (CsA) and sirolimus (SRL, rapamycin) on the tissue
      distributions of CsA and SRL in the rat. Groups of four adult male Wistar-Furth
      rats were treated for 14 days with 2.5, 5.0, or 10.0 mg CsA/kg x day. Other
      groups of four adult male Wistar-Furth rats were treated for 14 days with a 1-to
      6.25 weight-to-weight ratio of SRL to CsA at SRL doses of 0.4, 0.8, or 1.6 mg/kg
      x day. Concentrations of CsA and SRL in homogenates of heart, intestinal, kidney,
      liver, lung, muscle, spleen, and testes were compared to those in whole blood
      (WB). There was a large, dose-dependent, distinctive distribution of CsA among
      rat tissues, as has previously been well documented. At a constant molar dose
      ratio, concomitant oral administration of SRL produced an approximately two-fold
      increase in the concentrations of CsA in rat tissues, although SRL did not change
      the CsA tissue-to-WB partition coefficients. Concomitant oral CsA administration
      produced dose-dependent increases in SRL tissue concentrations and decreases in
      the SRL tissue-to-WB partition coefficients. The increases in tissue and WB
      concentrations on coadministration of both agents may be explained either by an
      increase in absorption caused by competition between the two agents for binding
      sites on P-glycoprotein in the gut, a reduced rate of metabolism, or to an as yet
      unidentified elimination mechanism. The dose-independent and unchanged CsA tissue
      to-WB partition coefficients suggest that SRL does not affect the equilibrium of
      CsA between the central and tissue compartments, namely the tissue uptake or
      intracellular binding. Altered values of the SRL tissue-to-WB partition
      coefficients suggest that, under the conditions studied, CsA disturbs the
      equilibrium of SRL between the central and tissue compartments.

PMID- 9558126
TI  - A model for the prediction of digoxin-drug interactions at the renal tubular cell
      level.
AB  - Digoxin-drug interactions are relatively common causes of digitalis toxicity.
      Recently, the clinical importance of the renal tubular secretion of digoxin has
      been proven by documenting drug interactions at this level. The authors describe
      a model using cultured renal tubular cell monolayers that can be used to predict
      drug interactions with the cardiac glycoside. This model accurately documents
      known clinical digoxin interactions such as those with verapamil and propafenone.
      The common feature of these interactions is that they involve P-glycoprotein
      substrates (e.g., digoxin, vincristine, vinblastine) or inhibitors (e.g.,
      quinidine, cyclosporine). In the case of the newly described interaction of
      digoxin with itraconazole, the model preceded the emergence of clinical cases.

PMID- 9558127
TI  - Population pharmacokinetics of vancomycin in Japanese adult patients.
AB  - Population pharmacokinetic parameters of vancomycin (VCM) in Japanese adult
      patients infected with methicillin-resistant Staphylococcus aureus (MRSA) were
      estimated using 1253 items of serum concentration data from 190 patients obtained
      in routine drug monitoring. The two-compartment linear model was adopted, and VCM
      clearance (CL) was correlated with the creatinine clearance (CLcr), which was
      observed or estimated by the Cockcroft-Gault equation. The population
      pharmacokinetic analysis program NONMEM with first-order conditional estimation
      method was used. The results showed VCM clearance to be linearly correlated with
      CLcr (CL [ml/min] = 0.797 x CLcr) when the estimated CLcr was <85 ml/min, but no
      linear relationship at higher than this level because of the lack of accuracy in
      the CLcr estimates. The interindividual variability of CL was 38.5%; K12 and K21
      were 0.525 hr(-1) and 0.213 hr(-1), respectively. The distribution volume at
      steady state (V[SS]) was 60.71, with no significant dependence on the actual body
      weight. The interindividual variability of Vss was 25.4%. The calculated half
      life (t1/2,beta) in a typical patient with CLcr of 85 ml/minute was 12.8 hours.
      Residual variability was 23.7%. These results were compared to those of healthy
      volunteers, and guidelines for dosage adjustment in VCM therapy are discussed.

PMID- 9558128
TI  - Valproate as monotherapy for juvenile myoclonic epilepsy: dose-effect study.
AB  - Sodium valproate enteric-coated tablets were used in this double-blind,
      randomized, cross-over study of 16 patients with juvenile myoclonic epilepsy
      comparing 1000 mg and 2000 mg VPA daily in b.i.d. administration with 6 months of
      observation on each dose. Myoclonic, absence, and generalized tonic-clonic
      seizures were registered separately. Subjective side-effects were monitored, and
      a computerized neuropsychologic test battery was performed on each dose. There
      was no significant difference in seizure frequency between the two doses. Only
      25% of the patients were seizure free throughout the study despite concentrations
      well within the normally proposed therapeutic range for VPA. During the higher
      dose, 37.5% of the patients had an improved seizure control, but 25% of the
      patients had an increase in seizure frequency compared to the lower dose.
      However, there was no correlation between VPA concentrations and subjective side
      effects or neuropsychologic test results. Our observations point out the
      possibility that the common strategy of increasing plasma levels in difficult-to
      treat patients until side effects occur should perhaps be reconsidered, but this
      suggestion needs further confirmation.

PMID- 9558129
TI  - A population pharmacokinetic model of cyclosporine in the early postoperative
      phase in patients with liver transplants, and its predictive performance with
      Bayesian fitting.
AB  - The availability of personal computer programs to individualize drug regimens has
      stimulated interest in modeling population pharmacokinetics. This study used the
      NPEM2 software to determine cyclosporine population pharmacokinetic parameter
      values and distributions in a first group of 25 recipients of liver transplants
      during their first postoperative week. On a second group of 25 patients, the
      authors used these values to evaluate Bayesian predictive performance of
      cyclosporine blood concentrations with the USC*PACK PC program. During the study
      period, all the patients have been treated by continuous intravenous infusion.
      The one-compartment model pharmacokinetic parameter-the slope of volume to body
      weight (Vs) and the elimination rate constant (Kel) values found (mean values: Vs
      = 2.177 l/kg, Kel = 0.235 h(-1); median values: Vs = 1.559 l/kg, Kel = 0.163 h(
      1); the percent coefficient of variation (Vs = 92%, Kel = 79%) appear reasonable
      and show the ability of NPEM2 to deal with sparse data. When the predictions were
      studied with day 1, day 2, or day 3 concentrations, predictive bias was
      respectively -0.030, -0.013, and 0.013 microg/ml, suggesting a greater clearance
      of cyclosporine immediately after surgery, the clearance decreasing in the days
      after. With the first three blood levels and the Bayesian fitting procedure, it
      was possible to predict at least half the subsequent measured blood levels of
      each patient accurately (within 20%) in more than three-quarters (76%) of the
      second group of recipients of transplants, and for 40% of patients the authors
      obtained accurate predictions in 100% of the subsequent blood levels. For a few
      patients (12%) they found quite poor predictions. The reason for this is unclear.
      The results suggest that this population model and the Bayesian fitting procedure
      using two or three blood levels can be reasonably and carefully used to control,
      in real time, cyclosporine blood levels in a majority of new patients with liver
      transplants.

PMID- 9558130
TI  - Ability of a first-pass pharmacokinetic model to characterize cyclosporine blood
      concentrations after administrations of Sandimmune or Neoral formulations.
AB  - Most recent cyclosporine (CsA) pharmacokinetic (PK) studies have focused on
      noncompartmental analysis. Because CsA undergoes significant first-pass
      elimination after oral dosing, the most appropriate compartment model may need to
      take this process into account for the construction of a valid population PK
      model for Sandimmune (SAN) and Neoral (NEO) formulations. Twenty patients with
      cardiac transplants were stabilized for at least 4 weeks on a certain dose of
      SAN, then changed to the same daily dose of NEO. Blood samples were obtained at
      times 0, 1, 2, 3, 4, 6 and 12 hours after dosing at steady state. Pharmacokinetic
      modeling was performed using ADAPT II. Quality of fit was assessed by visual
      graph inspections, R2 values, and Akaike criterion test. Eight pharmacokinetic
      models were constructed and evaluated. These included one- and two-compartment
      with and without a first-pass effect and a time-lag. Neoral and SAN data were
      consistently best fitted using a two-compartment or the two-compartment first
      pass model. However, a time-lag process was found to be necessary for SAN. The
      use of a two-compartment first-pass with (SAN) or without (NEO) a time-lag
      process appears to fit CsA concentrations at least as well as a two-compartment
      model. This first-pass model may be very useful for population pharmacokinetics
      and Bayesian control analysis.

PMID- 9558131
TI  - Safety and efficacy of a two-compartment Bayesian feedback program for
      therapeutic tobramycin monitoring in the daily clinical use and comparison with a
      non-Bayesian one-compartment model.
AB  - The predictive value of a two-compartment Bayesian feedback program for
      tobramycin dose optimization was retrospectively evaluated in 199 hospitalized
      patients and compared with that of a simple non-Bayesian one-compartment model.
      Before dose adjustment, 64% of the patients were underdosed indicating that
      tobramycin monitoring is still necessary to avoid ineffective antibiotic therapy.
      When physicians adhered to the dose instructions calculated with the Bayesian
      method, 90% of the patients had optimal concentration-time profiles as opposed to
      only 53% of the 43 patients in whom dose recommendations were not followed. In
      young patients with normal renal function, precision and accuracy of the Bayesian
      feedback and the one-compartment method were well correlated, whereas in elderly
      patients (> 60 years) and patients with impaired renal function (estimated
      creatinine clearance < 60 ml/minute), the Bayesian method was significantly more
      precise. Multiple regression analysis revealed that renal function was the only
      independent variable predicting the performance of the Bayesian program. The
      results of this study indicate that the Bayesian feedback method is a reliable
      method for the therapeutic tobramycin monitoring under clinical conditions and in
      particular, elderly patients in whom renal impairment is frequent.

PMID- 9558132
TI  - Correlation between concentrations of melatonin in saliva and serum in patients
      with delayed sleep phase syndrome.
AB  - Exogenous melatonin, which can be used to treat certain circadian rhythm
      disorders, maximally advances delayed rhythms when administered 5 hours before
      the endogenous melatonin starts to increase. The time of the start of the
      endogenously melatonin is defined as Dim Light Melatonin Onset (DLMO). The DLMO
      concentration has been defined in serum to be 10 pg/ml. Because of the greater
      practicability of frequent saliva sampling over blood sampling, we have validated
      radioimmunoassay (RIA) measurements of melatonin in saliva in patients diagnosed
      as suffering from a typical circadian rhythm disorder: Delayed Sleep Phase
      Syndrome (DSPS). Based on these results we have defined the equivalent salivary
      DLMO concentration to be 4 pg/ml.

PMID- 9558133
TI  - Population pharmacokinetic parameters of gentamicin in patients with solid
      tumors: estimation by one- and two-stage methods.
AB  - Gentamicin monitoring has been improved with the introduction of Bayesian methods
      but the usefulness depends on the quality of the population parameters (PP) used.
      The objective of this study was to determine PP of gentamicin in patients with
      solid tumors. A total of 198 adult patients with cancer were included in the
      analysis. Population parameters were estimated by both a two-stage and a one
      stage method (NPEM, Non Parametric Expectation Maximization). Individual
      parameters (IP) were estimated by the Sawchuk-Zaske method and by nonlinear
      regression. The estimated distribution volume and clearance of gentamicin (mean
      +/- SD) were 18.37 +/- 5.021 (0.30-0.32 l/kg of dosing weight) and 3.34 +/- 1.6
      l/h, respectively. No significant differences between IP or PP obtained by the
      different methods were found. The results indicated a wide variability of
      gentamicin pharmacokinetics making monitoring necessary and that patients with
      solid tumors may have larger gentamicin volume and slower clearance than normal
      patients. These observations imply that different population pharmacokinetic
      parameters should be used for this group of patients.

PMID- 9558134
TI  - Development of a quantitative vancomycin immunoassay for the Abbott AxSYM
      analyzer.
AB  - A novel fluorescence polarization immunoassay for vancomycin on Abbott AxSYM
      analyzer is described. The immunoassay allows for the accurate quantification of
      vancomycin in the presence of the crystalline degradation product (CDP). It
      displays dilution linearity from 1.0 microg/ml to 100.0 microg/ml, coefficients
      of variation ranging from 2.94% to 4.26%, recovery from 98% to 105%, and a
      sensitivity of <2.0 microg/ml. The assay demonstrates no cross-reactivity to
      crystalline degradation product, and to commonly-prescribed and over-the-counter
      drugs, as well as a minimum interference from endogenous substances.

PMID- 9558135
TI  - Abbott AxSYM Vancomycin II assay: multicenter evaluation and interference
      studies.
AB  - The authors evaluated the performance characteristics of the Abbott AxSYM
      Vancomycin II immunoassay in sera of patients with (n = 93 samples) and without
      (n = 327 patients) renal dysfunction. Correlation of vancomycin measurements with
      the Abbott AxSYM Vancomycin, Abbott TDx/TDxFLx, Syva enzyme-multiplied
      immunoassay technique (EMIT), DuPont automated chemistry analyzer (ACA), and high
      performance liquid chromatography methods showed acceptable correlation as
      indicated by: slope values >0.95, r-values >0.97, y-intercepts <1.7 microg/ml,
      and S(y/x) ranging from 9% to 15% of the average vancomycin value. The AxSYM
      Vancomycin II assay showed acceptable correlation with AxSYM vancomycin,
      TDx/TDxFLx, and high-performance liquid chromatography methods in 93 samples from
      patients with renal dysfunction. This monoclonal antibody-based assay showed no
      apparent interference from the presence of human antimouse antibody (HAMA) or the
      microbiologically inactive vancomycin crystalline degradation product (CDP). The
      authors conclude that the AxSYM Vancomycin II assay showed satisfactory agreement
      with other methods tested in this study.

PMID- 9558136
TI  - Determination of lamotrigine in biologic materials by a simple and rapid liquid
      chromatographic method.
AB  - Lamotrigine (LTG), a newly introduced antiepileptic drug, appears to have
      potential therapeutic advantages for the treatment of patients with partial-onset
      seizures. Increasing clinical application and research of LTG demand a simpler
      and more rapid analytical procedure to determine LTG concentration in body fluids
      and tissues. The authors have developed an effective one-step procedure for
      sample preparation followed by high-performance liquid chromatography (HPLC) to
      quantitate LTG in plasma, urine, and brain tissues. Body fluids and brain
      homogenates were treated with cold acetonitrile to precipitate protein. The
      samples were fractionated on a 250 x 4.6 mm C18 reversed-phase column with an
      isocratic mobile system consisting of potassium phosphate buffer, acetonitrile,
      and methanol (70:16:14). The method had a LTG detection limit of 0.02 microg/ml
      in plasma and 0.03 microg/ml in urine. The coefficients of variation were <2.7%
      for intraday and 4.2% for interday analyses. The recovery of LTG added to plasma,
      urine, and brain homogenate ranged from 98% to 100%. The method was applied to a
      clinical study to determine plasma and urine concentrations of LTG in subjects
      receiving a single oral dose of LTG. The calculated pharmacokinetic parameters
      were comparable to those previously reported. The method proved to be simple,
      fast, reproducible, and useful in clinical investigation and monitoring of LTG
      concentrations.

PMID- 9558137
TI  - Improved one-step solid-phase extraction method for morphine, morphine-3
      glucuronide, and morphine-6-glucuronide from plasma and quantitation using high
      performance liquid chromatography with electrochemical detection.
AB  - This communication describes an improved one-step solid-phase extraction method
      for the recovery of morphine (M), morphine-3-glucuronide (M3G), and morphine-6
      glucuronide (M6G) from human plasma with reduced coextraction of endogenous
      plasma constituents, compared to that of the authors' previously reported method.
      The magnitude of the peak caused by endogenous plasma components in the
      chromatogram that eluted immediately before the retention time of M3G has been
      reduced (approximately 80%) significantly (p < 0.01) while achieving high
      extraction efficiencies for the compounds of interest, viz morphine, M6G, and M3G
      (93.8 +/- 2.5, 91.7 +/- 1.7, and 93.1 +/- 2.2%, respectively). Furthermore, when
      the improved solid-phase extraction method was used, the extraction cartridge
      derived late-eluting peak (retention time 90 to 100 minutes) reported in our
      previous method, was no longer present in the plasma extracts. Therefore the
      combined effect of reducing the recovery of the endogenous components of plasma
      that chromatographed just before the retention time of M3G and the removal of the
      late-eluting, extraction cartridge-derived peak has resulted in a decrease in the
      chromatographic run-time to 20 minutes, thereby increasing the sample throughput
      by up to 100%.

PMID- 9558138
TI  - An abbreviated area-under-the-curve monitoring for tacrolimus in patients with
      liver transplants.
AB  - This study aims to assess the predictability of individual tacrolimus (FK)
      concentrations at different time points for the area under the curve (AUC) and to
      find the best sampling time for the abbreviated AUC to predict the total body
      exposure of FK. A total of 23 FK blood concentration versus time profiles (11
      blood samples per 12 hours) was studied in 12 stable patients with liver
      transplants at steady state. Each AUC was calculated by the trapezoidal rule, and
      the relationship between individual concentrations or abbreviated AUC and total
      AUC was determined by linear regression. The trough concentrations from the
      morning dose predict AUC better than the trough concentration from the evening
      dose (r2 = 0.71 for morning dose and r2 = 0.35 for evening dose). In the case of
      single drug concentration, the 4-hour concentration could predict the total AUC
      reasonably well (r2 = 0.73). From stepwise multiple regression, the abbreviated
      AUC at 1, 2.5, 6, and 9 hours could predict the total AUC most accurately (r2 =
      0.99). This study shows that the four levels at 1, 2.5, 6, and 9 hours or 1, 4,
      and 12 hours as an abbreviated AUC is as good as a full pharmacokinetic study.
      Alternatively, 4-hour concentration is a good predictor of the total body
      exposure of FK in the stable patients with liver transplants.

PMID- 9558140
TI  - New modified fluorescence polarization immunoassay does not falsely elevate
      vancomycin concentrations in patients with end-stage renal disease.
AB  - Recent literature has urged caution in the interpretation of vancomycin serum
      concentrations in patients with end-stage renal disease (ESRD), because falsely
      elevated levels in excess of 70% have been reported with the most commonly used
      fluorescence polarization immunoassay (FPIA). The purpose of this study was to
      evaluate the performance of a recently modified FPIA assay for use in patients
      with ESRD, in comparison to high-performance liquid chromatography (HPLC) and an
      enzyme-mediated immunoassay technique (EMIT). Serum vancomycin samples were
      prospectively collected from adults with ESRD undergoing chronic hemodialysis.
      Each sample was stored at -70 degrees C until analyzed in duplicate by FPIA,
      EMIT, and HPLC. In an in vitro experiment, blank serum samples with 15 microg/ml
      vancomycin were spiked with increasing amounts of CDP and analyzed in duplicate
      with the modified FPIA assay. When compared to HPLC, no statistically significant
      difference was found in patients with ESRD with the use of the modified FPIA
      assay (mean concentrations, HPLC 14.92 microg/ml, FPIA 15.96 microg/ml), with
      FPIA exhibiting a positive bias of 0.64 microg/ml and a precision of +/-3.49
      microg/ml (n = 18, p = 0.44). The mean EMIT concentration was 18.34 microg/ml,
      with a positive bias of 3.43 microg/ml and a precision of +/-5.17 microg/ml (p <
      0.01). The addition of increasing amounts of CDP to vancomycin in vitro resulted
      in concentrations similar to those expected in the absence of significant cross
      reactivity with the modified FPIA assay. The modified FPIA assay is a
      satisfactory tool for monitoring vancomycin serum concentrations in patients with
      ESRD undergoing hemodialysis. Results obtained with EMIT were not as precise as
      with FPIA.

PMID- 9558139
TI  - Comparison of two high-performance liquid chromatographic methods for monitoring
      plasma concentrations of haloperidol and reduced haloperidol.
AB  - Two high-performance liquid chromatographic methods for monitoring haloperidol
      (HAL) and reduced haloperidol (RHAL) plasma concentrations were compared. In one
      method ultraviolet detection and a C18 column were used (UV method); in the other
      method electrochemical detection and a CN-column were used (EC method). Both
      methods are accurate and precise. For plasma samples spiked with HAL or RHAL, an
      excellent correlation was observed between the concentrations of HAL and RHAL
      found with both methods (r < or = 0.99, p < 0.01). However, for plasma obtained
      from patients treated with HAL the correlation between the two methods was poor
      (r > or = 0.71, p < 0.01). The main reason for the discrepancy between the two
      methods is probably interference of comedications or their metabolites, mostly in
      the EC method. Although the quantitation limit of the UV method (2 ng/ml for HAL
      and RHAL) is higher than that of the EC method (0.5 ng/ml for HAL and RHAL), the
      UV method is to be preferred for monitoring plasma levels in psychiatric patients
      because there is less interference from comedication.

PMID- 9558141
TI  - Successful therapy of refractory graft versus host disease with tacrolimus and
      Psoralen plus ultraviolet light.
AB  - The authors report a patient who developed severe graft versus host disease
      (GVHD) after undergoing a matched, unrelated bone marrow transplant. Her symptoms
      worsened despite treatment with cyclosporine, high doses of methylprednisolone,
      and antithymocyte globulin. After treatment with tacrolimus (FK506) and Psoralen
      plus ultraviolet light (PUVA), there was complete resolution of all clinical and
      laboratory evidence of GVHD. This combination may be beneficial to other patients
      who develop severe GVHD that is resistant to conventional therapy.

PMID- 9558142
TI  - Therapeutic drug monitoring of tacrolimus (FK506) using tandem mass spectrometry.

PMID- 9558143
TI  - Consensus report of the Working Group on: "Molecular and Biochemical Markers of
      Alzheimer's Disease". The Ronald and Nancy Reagan Research Institute of the
      Alzheimer's Association and the National Institute on Aging Working Group.
AB  - The ideal biomarker for Alzheimer's disease (AD) should detect a fundamental
      feature of neuropathology and be validated in neuropathologically-confirmed
      cases; it should have a sensitivity >80% for detecting AD and a specificity of
      >80% for distinguishing other dementias; it should be reliable, reproducible, non
      invasive, simple to perform, and inexpensive. Recommended steps to establish a
      biomarker include confirmation by at least two independent studies conducted by
      qualified investigators with the results published in peer-reviewed journals. Our
      review of current candidate markers indicates that for suspected early-onset
      familial AD, it is appropriate to search for mutations in the presenilin 1,
      presenilin 2, and amyloid precursor protein genes. Individuals with these
      mutations typically have increased levels of the amyloid Abeta42 peptide in
      plasma and decreased levels of APPs in cerebrospinal fluid. In late-onset and
      sporadic AD, these measures are not useful, but detecting an apolipoprotein E e4
      allele can add confidence to the clinical diagnosis. Among the other proposed
      molecular and biochemical markers for sporadic AD, cerebrospinal fluid assays
      showing low levels of Abeta42 and high levels of tau come closest to fulfilling
      criteria for a useful biomarker.

PMID- 9558144
TI  - CSF tau and Abeta42: logical biomarkers for Alzheimer's disease?

PMID- 9558145
TI  - Methodological and research issues in the evaluation of biological diagnostic
      markers for Alzheimer's disease.

PMID- 9558147
TI  - The development of biological markers for the diagnosis of Alzheimer's disease.

PMID- 9558146
TI  - Cerebrospinal fluid tau protein as a potential diagnostic marker in Alzheimer's
      disease.

PMID- 9558148
TI  - Diagnostic markers for Alzheimer's disease.

PMID- 9558149
TI  - Role of genetics in tests of genotype, status, and disease progression in early
      onset Alzheimer's disease.

PMID- 9558150
TI  - Evaluation and use of diagnostic tests in Alzheimer's disease.

PMID- 9558151
TI  - Biological markers of Alzheimer's disease.

PMID- 9558152
TI  - Biological markers of Alzheimer's disease.

PMID- 9558153
TI  - Some remarks on biological markers of Alzheimer's disease.

PMID- 9558154
TI  - Biomarkers in Alzheimer's disease.

PMID- 9558155
TI  - Amyloid beta protein in plasma as a diagnostic marker for Alzheimer's disease.

PMID- 9558156
TI  - Biochemical diagnostic markers to detect early Alzheimer's disease.

PMID- 9558157
TI  - Managed care and the practice of rheumatology.

PMID- 9558158
TI  - Persistent Chlamydia trachomatis infection: in vitro phenomenon or in vivo
      trigger of reactive arthritis?

PMID- 9558159
TI  - Transforming growth factor-beta and platelet derived growth factor regulation of
      fibrillar fibronectin matrix formation by synovial fibroblasts.
AB  - OBJECTIVE: To investigate factors regulating fibronectin fibrillar matrix
      formation by synovial fibroblasts. METHODS: Basal and cytokine stimulated
      extracellular matrix (ECM) fibronectin produced by synovial fibroblasts was
      identified by immunofluorescence and Western blot. Alternative mRNA splicing of
      fibronectin was studied by reverse transcription polymerase chain reaction. The
      integrin receptor responsible for supporting fibronectin fibrillar matrix was
      identified by blocking antibodies and receptor levels studied by Western blot.
      RESULTS: Transforming growth factor-beta (TGF-beta) or platelet derived growth
      factor (PDGF), but not interleukin 1 or exogenous fibronectin, induced ECM
      fibronectin. ECM fibronectin was blocked by the addition of antibody to the
      alpha5beta1 integrin. Cytokines did not significantly change alternative mRNA
      splicing of fibronectin or levels of alpha5beta1 integrin expression. CONCLUSION:
      Synovial cell production of a fibrillar fibronectin matrix is induced by growth
      factors, including TGF-beta and PDGF. This induction is mediated by the
      alpha5beta1 integrin. Since fibrillar fibronectin formation was not strongly
      dependent on increased fibronectin or alpha5beta1 integrin levels, this effect
      may be mediated by growth factor induced changes in receptor affinity.

PMID- 9558160
TI  - Infrequent detection of cytomegalovirus and Epstein-Barr virus DNA in synovial
      membrane of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To study the role of the cytomegalovirus (CMV), Epstein-Barr virus
      (EBV), herpes simplex virus types 1 and 2 (HSV-1 and 2), varicella zoster virus
      (VZV), and human herpes virus 6 (HHV-6) in the etiology of rheumatoid arthritis
      (RA). METHODS: Polymerase chain reaction (PCR) was used to detect DNA of the
      different herpes viruses in synovial membranes from 31 patients with chronic RA
      and 14 control patients. Specific antibodies were determined by indirect
      immunofluorescence and ELISA. RESULTS: Out of 31 patients with RA, CMV DNA was
      detected in synovial membranes from 2 patients and EBV DNA was detected in
      synovial membranes from 2 other patients. All samples from the patients with RA
      were negative for DNA from HSV-1 and 2, VZV, and HHV-6. All samples from the 14
      control patients were negative in all PCR assays. No statistically significant
      differences in IgG antibodies were found for CMV, HSV-1, VZV, and HHV-6 in
      patients with RA compared to controls. Higher titers of IgG antibodies against
      EBV viral capsid antigen were found in patients with RA, with a significance of p
      < 0.05. CONCLUSION: Both CMV and EBV DNA were detected in synovial membranes from
      6% of the patients with RA. We cannot exclude the possibility that these viruses
      were associated with disease development in a minority of patients with RA.

PMID- 9558161
TI  - Mannan binding lectin in rheumatoid arthritis. A longitudinal study.
AB  - OBJECTIVE: Low serum levels of mannan binding lectin (MBL) are associated with
      increased risk of recurrent infections. We determined whether there was an
      association between serum MBL levels and the course and prognosis of rheumatoid
      arthritis (RA). METHODS: MBL was analyzed in sera from 99 patients with RA who
      were included in a longterm prospective study. RESULTS: Compared with controls, a
      high fraction of patients lacked detectable MBL in serum (11 vs 3%; p = 0.025).
      Comparing patients with MBL serum levels above and below the median revealed that
      those with levels below the median were younger at onset of RA (p = 0.043) and
      had higher erythrocyte sedimentation rate (p = 0.006), joint swelling score (p =
      0.019), limitation of joint motion score (p = 0.027), and annual increase in
      radiographic destruction score (p = 0.053). CONCLUSION: MBL insufficiency may be
      a contributing pathogenetic factor in RA.

PMID- 9558162
TI  - Early radiographic joint space narrowing and erosion and later malalignment in
      rheumatoid arthritis: a longitudinal analysis.
AB  - OBJECTIVE: To analyze the time course of development of radiographic erosion,
      joint space narrowing, and malalignment in a longitudinal study of radiographs of
      the hands and wrists of 58 patients with rheumatoid arthritis (RA) taken over 18
      years. METHODS: Among 210 consecutive patients in a reported cohort, 58 had at
      least one prior available radiograph 2-18 years earlier. A total of 141 hand and
      wrist radiographs in the 58 patients were scored for joint space narrowing,
      erosion, and malalignment in individual joints. RESULTS: Of the 58 patients
      studied, all developed joint space narrowing, 56 (96.5%) developed erosions,
      while only 24 (41.4%) developed malalignment. In radiographs of 22 patient
      studied within the first 5 years of disease, joint space narrowing was seen in 17
      (77.3%), erosion in 16 (72.7%), and malalignment in only 3 (13.6%). Radiographic
      progression was seen in all 36 patients in whom the interval between radiographs
      was longer than 2 years. CONCLUSION: Joint space narrowing and erosion are seen
      in hand radiographs of most patients with RA seen in treatment centers within the
      first 5 years of disease. By contrast, malalignment develops in fewer patients,
      and generally only after 5 years of disease.

PMID- 9558163
TI  - Longterm health outcomes of patients with rheumatoid arthritis treated in managed
      care and fee-for-service practice settings.
AB  - OBJECTIVE: To compare health care utilization and longterm health outcomes among
      patients with rheumatoid arthritis (RA) treated in managed care and fee-for
      service practice settings. METHODS: We compared levels of health care
      utilization, treatments, and health outcomes between 57 patients with RA treated
      predominantly in managed care settings and 125 patients with RA treated
      predominantly in fee-for-service practice settings. These patients were
      participants in a community based cohort study of health outcomes in RA, and had
      been followed prospectively for up to 13 years (mean followup 10.3 yrs).
      Information on physician visits, hospitalizations, diagnostic testing,
      treatments, and 3 measures of health status (global arthritis status, pain,
      functional disability measures of the Health Assessment Questionnaire) was
      collected using biannual mailed questionnaires. RESULTS: All measures of health
      care utilization were similar between the managed care and fee-for-service
      groups, as was the use of the major types of arthritis treatments. Average global
      arthritis status scores, pain scores, and functional disability scores were
      closely comparable in the 2 groups. Over time, global arthritis status scores and
      disability scores worsened in both groups, but the rates of worsening did not
      differ between groups. CONCLUSION: In this cohort, longterm health outcomes, as
      well as treatments and health care utilization, were similar among persons with
      RA who were treated in managed care and fee-for-service practice settings.

PMID- 9558165
TI  - SLICC/ACR Damage Index in Afro-Caribbean patients with systemic lupus
      erythematosus: changes in and relationship to disease activity, corticosteroid
      therapy, and prognosis.
AB  - OBJECTIVE: To apply the recently described Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR
      DI) in a well defined cohort of patients with systemic lupus erythematosus (SLE)
      and to study its association with disease activity, corticosteroid therapy, and
      prognosis. METHODS: We conducted a record review of 90 patients with SLE followed
      at a single center for a mean period of 6 years with periodic evaluations of SLE
      Disease Activity Index (SLEDAI), cumulative damage according to SLICC/ACR-DI, and
      therapy. Overall disease activity during the disease course was calculated as
      weighted averages of SLEDAI (WAS). RESULTS: Mean SLICC/ACR-DI was 0.6 six months
      after diagnosis and increased to 2.4 at last assessment. Thirteen patients (14%)
      remained free of accumulated damage at last visit. Index scores showed
      significant correlations with WAS scores and the number of disease exacerbations
      (SLEDAI > 10), but not with age, mean daily, or cumulative corticosteroid dosage.
      High WAS scores were independently associated with poorer survival, but SLICC/ACR
      DI scores were not. CONCLUSION: SLICC/ACR-DI scores correlate with overall
      disease activity, but not with length or intensity of corticosteroid therapy.
      While easily applicable, its prognostic value is subordinate to that of
      persistent disease activity.

PMID- 9558164
TI  - High seroprevalence of Helicobacter pylori infection in patients with systemic
      sclerosis: association with esophageal involvement.
AB  - OBJECTIVE: To determine the prevalence and clinical relevance of Helicobacter
      pylori infection in patients with systemic sclerosis (SSc). METHODS: Serum
      samples were obtained from 124 patients with SSc (67 with limited cutaneous SSc,
      57 with diffuse cutaneous SSc). Fifty samples from age and sex matched
      individuals were used as controls. IgG antibodies to H. pylori infection were
      measured by ELISA. RESULTS: IgG antibodies to H. pylori were found in 55.6% (69
      of 124) of the patients with SSc, significantly more than in the controls. There
      was a significant correlation of the presence of antibodies to H. pylori with the
      prevalence of esophageal hypomotility in the patients with SSc (p < 0.02).
      CONCLUSION: Patients with SSc have H. pylori infection at a higher prevalence
      than the general population. H. pylori might play a role in the development of
      esophageal dysfunction in SSc.

PMID- 9558166
TI  - The pathogenic 16/6 idiotype in patients with silica associated systemic lupus
      erythematosus (SLE) and uranium miners with increased risk for development of
      SLE.
AB  - OBJECTIVE: To investigate the prevalence of the 16/6 idiotype (16/6 Id), a major
      cross reactive idiotype of anti-DNA antibodies involved in the pathogenesis of
      experimental lupus, in subjects with an exogenous risk for the development of
      systemic lupus erythematosus (SLE). METHODS: The titer of 16/6 Id was determined
      by ELISA in sera of uranium miners exposed to heavy quartz dust: 15 developed
      definite and 12 probable SLE, 34 had clinical symptoms, and 27 had only
      serological signs (medium to high titer anti-dsDNA antibodies) of possible
      connective tissue disease (CTD) development. RESULTS: The prevalence of 16/6 Id
      was higher in all groups compared to healthy blood donors. It was 18.5% in miners
      with SLE (definite and probable) and 22.2-26.5% in miners with clinical and/or
      serological signs for developing CTD. All 16/6 Id positive miners were positive
      for anti-dsDNA antibodies and other autoantibodies associated with CTD. The
      prevalence of 16/6 Id in anti-dsDNA positive miners correlated slightly with
      CTD/SLE symptoms: 55.6% in patients with SLE, 47.4% in miners with possible
      CTD/SLE, and 22.2% in miners without CTD symptoms. Further, at short term
      followup, disease progressed in 2 miners of the 16/6 Id positive, but not in 16/6
      Id negative miners. CONCLUSION: The detection of 16/6 Id in miners exposed to
      quartz dust may indicate a higher risk for development of SLE, warranting further
      studies of the role of 16/6 Id in the development of SLE in a cohort with the
      same sex, ethnicity, geographic region, and occupation.

PMID- 9558168
TI  - High frequency of abnormal levels of IgA anti-beta2-glycoprotein I antibodies in
      patients with systemic lupus erythematosus: relationship with antiphospholipid
      syndrome.
AB  - OBJECTIVE: To determine the frequency of IgA, in addition to IgM and IgG, anti
      beta2-GPI and anticardiolipin (aCL) antibodies in patients with systemic lupus
      erythematosus (SLE), and to relate the presence of these antibodies to symptoms
      of antiphospholipid antibody syndrome (APS). METHODS: Sera from 100 blood bank
      donors (controls) and 48 patients with SLE were tested by ELISA. The same enzyme
      conjugates were used in the measurement of aCL and anti-beta2-GPI. Medical
      records were reviewed for the presence of manifestations of APS: arterial
      occlusion, pulmonary embolism, cerebrovascular accident, transient ischemic
      attack, venous thrombosis (deep or superficial), hemolytic anemia,
      thrombocytopenia, repeated fetal loss, leg ulcers, seizures, avascular bone
      necrosis, cerebritis, or migraine. RESULTS: Above normal levels of antibodies of
      all 3 isotypes against beta2-GPI were found in 5% of controls and 73% of patients
      with SLE. Antibodies against cardiolipin in the 2 groups were found in 5 and 37%,
      respectively. IgA anti-beta2-GPI was found in 2% of controls and 58% of patients
      with SLE; in contrast, only 2% of patients with SLE had IgA aCL. In the 48
      patients studied, thrombosis and fetal loss were present in 10 (Group 1), other
      manifestations of APS were present in 18 (Group 2), and none in 20 (Group 3).
      Antibodies to beta2-GPI of all 3 isotypes were found in a higher proportion of
      APS (Group 1 plus Group 2) (82%) than in Group 3 (50%) (p < 0.01, chi-squared).
      There was also a significantly higher proportion of patients with elevated anti
      beta2-GPI in Group 1 (90%) than in Group 3 (p < 0.02). There was a significantly
      higher frequency (p < 0.01) and level (p < 0.05) of IgA anti-beta2-GPI in
      patients with APS than in those with no APS manifestations. Moreover, compared to
      aCL and with other isotypes of anti-beta2-GPI, the highest antibody levels were
      observed in IgA antibeta2-GPI. CONCLUSION: The sensitivity of the anti-beta2-GPI
      antibody test for APS in patients with SLE is significantly increased by
      measuring IgA, in addition to IgM and IgG isotype.

PMID- 9558167
TI  - Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and
      primary antiphospholipid antibody syndrome: clinical correlations in comparison
      with other antiphospholipid antibody tests.
AB  - OBJECTIVE: To examine relationships between anti-beta2-glycoprotein (beta2-GPI)
      antibodies and other antiphospholipid antibody (aPL) tests (aPL ELISA and the
      lupus anticoagulant or LAC) and the associations of each of these aPL tests with
      individual clinical manifestations of the antiphospholipid antibody syndrome
      (APS). METHODS: IgG and IgM anti-beta2-GPI antibodies were determined by ELISA in
      281 patients with SLE, primary APS, or other connective tissue diseases.
      Frequencies, sensitivities, specificities, and predictive values and correlations
      of anti-beta2-GPI were compared to the aPL ELISA (IgG and IgM) and LAC for
      individual (and combined) features of APS. RESULTS: Among 139 patients with
      positive aPL ELISA and/or LAC tests, 57 (41%) had anti-beta2-GPI antibodies (IgG
      and/or IgM) compared to 11% of patients with SLE negative for these tests (p =
      0.00001). In 130 patients with APS, anti-beta2-GPI occurred in 42% and tended to
      be more specific but less sensitive than the aPL ELISA or LAC. When all 3 aPL
      tests were combined, the best sensitivities and negative predictive values were
      achieved; however, specificity and positive predictive values remained low. Anti
      beta2-GPI antibodies occurred more frequently in primary APS (58%) vs secondary
      antiphospholipid syndromes (33%) (p = 0.008, OR = 2.9). Among 79 patients with
      SLE negative by both aPL ELISA and LAC, 9 (11 %) were positive for anti-beta2
      GPI, 7 of whom had clinical features consistent with APS (representing 5% of all
      with APS). Stepwise multiple logistic regression analysis revealed beta2-GPI to
      be most strongly associated with neurological syndromes other than stroke, deep
      venous thrombosis, and recurrent fetal loss, while LAC was most strongly
      correlated with stroke and thrombocytopenia. IgM aPL antibodies also were
      independently associated with neurological syndromes and recurrent fetal loss.
      CONCLUSION: Testing for beta2-GPI antibodies may be clinically useful in the
      diagnosis of APS but cannot supplant other aPL ELISA or LAC. Multivariate
      analyses suggest that anti-beta2-GPI antibodies may play a more central role in
      certain clinical manifestations of APS than antibodies detected by the aPL ELISA
      or LAC.

PMID- 9558169
TI  - A close temporal relationship of liver disease to antiribosomal P0 protein
      antibodies and central nervous system disease in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine whether there is a close temporal relationship of liver
      disease to serum IgG and/or IgM antiribosomal P0 protein antibodies (anti-P0) and
      central nervous system (CNS) lupus in patients with systemic lupus erythematosus
      (SLE). METHODS: The study included 70 patients with active SLE. Of these, 30 had
      IgG and/or IgM anti-P0 and 14 had CNS lupus other than psychiatric disease
      (nonpsychiatric CNS lupus). Of these 14 patients, 11 had anti-P0. Laboratory
      manifestations of liver disease were retrospectively analyzed. RESULTS: Liver
      disease not attributed to any cause other than SLE (SLE liver disease) was
      present in 8 of the 11 patients with anti-P0 with nonpsychiatric CNS lupus
      (72.7%), in none of the 19 patients with anti-P0 without nonpsychiatric CNS lupus
      (0%), and in one of the 40 patients without anti-P0 (2.5%). The prevalence of SLE
      liver disease was significantly greater in patients with anti-P0 with
      nonpsychiatric CNS lupus than in the other 2 groups (p < 0.0001). Mean levels of
      liver enzymes (lactate dehydrogenase, glutamic oxaloacetic transaminase,
      glutamate pyruvate transaminase, gammaglutamyl transpeptidase) were significantly
      higher in patients with anti-P0 with nonpsychiatric CNS lupus than in the other 2
      groups. Serial studies in 3 patients showed that the appearance of anti-P0 and
      liver dysfunction slightly preceded the onset of nonpsychiatric CNS lupus.
      CONCLUSION: Anti-P0 may be related to the pathogenesis of CNS lupus and SLE liver
      disease found simultaneously in SLE. The appearance of anti-P0 and liver
      dysfunction may predict onset of CNS lupus.

PMID- 9558170
TI  - Decreased Fcgamma receptor III (CD16) expression on peripheral blood mononuclear
      cells in patients with Sjogren's syndrome.
AB  - OBJECTIVE: To examine the expression of surface structures important in natural
      killer (NK) cell function and the roles of serum factors affecting the expression
      of surface antigens on these cells in patients with Sjogren's syndrome (SS).
      METHODS: Peripheral blood mononuclear cells (PBMC) of 18 patients with SS were
      analyzed by immunofluorescence on a flow cytometer. The antigen recognized by
      autoantibodies in their sera was analyzed by immunofluorescence and by
      immunoprecipitation. RESULTS: Expression of Fcgamma receptor III (CD16), an
      important indicator of NK cytolytic activity, on PBMC was significantly decreased
      in patients with SS who have extraglandular disease, while the expression of
      Fcgamma RI and II was normal. Moreover, F(ab')2 of IgG in these patients' sera
      was shown to bind to CD16+ cells. Immunoprecipitation study showed that it bound
      to CD16 itself. CONCLUSION: The depressed expression of CD16 on PBMC and the
      presence of antibody binding to CD16 in the patients' sera may be, at least in
      part, responsible for the altered function of NK cells observed in SS.

PMID- 9558171
TI  - Prevalence of Raynaud's phenomenon in 2 ethnic groups in the general population
      of Estonia.
AB  - OBJECTIVE: To compare the prevalence of Raynaud's phenomenon (RP) in 2
      genetically different ethnic groups in Estonia: Estonians, who are Finno-Ugric
      people, and Slavs, who are Indo-European people, and to investigate the risk
      factors of RP. METHODS: A random sample of 5248 Estonians and 4341 Slavs were
      surveyed by mail questionnaire (Phase I) for suspected RP. A subsample of 1739
      subjects was interviewed and examined (Phase II) to make a formal diagnosis of
      RP, using the color charts, and to collect additional pertinent information.
      RESULTS: Of these 1739 subjects examined in Phase II, 226 women and 162 men were
      diagnosed to have RP. The age adjusted prevalence of RP was significantly higher
      among Slavs (women 11.4 +/- 1.3%, men 13.0 +/- 1.6%) compared to Estonians (women
      7.8 +/- 1.0%, p = 0.023; men 8.2 +/- 1.5%, p = 0.031). Based on logistic
      regression analysis, the diagnosis of RP among women was associated with a Slavic
      ethnic origin, the presence of connective tissue disorders or cardiovascular
      diseases, a family history of RP, a history of dysphagia and frostbite, smoking,
      and a lower body mass index (BMI). Among men RP was associated with manual work,
      vibrating tool use, a history of frostbite and injuries to the fingers. older
      age, and a lower BMI. CONCLUSION: Our results revealed a significant difference
      in the prevalence of RP between 2 ethnic groups living in the same geographic
      region. The risk factors associated with RP show considerable sex differences, RP
      being mostly constitutional in women and occupational in men.

PMID- 9558173
TI  - Human neutrophil elastase in temporal (giant cell) arteritis: plasma and
      immunohistochemical studies.
AB  - OBJECTIVE: Few enzymes are able to attack the internal elastic lamina, which is
      destroyed in temporal arteritis (TA). Because human neutrophil elastase (HNE) is
      one of these, its role in the pathogenesis of TA was examined in patients
      undergoing temporal artery biopsy for suspected TA. METHODS: Over a 6 month
      period, 33 patients undergoing temporal artery biopsy were prospectively included
      in the study. TA was diagnosed in 15 patients; 9 of them had positive temporal
      artery biopsy. The other 18 patients made up the non-TA group. Nineteen healthy
      age matched subjects (mean age 74 +/- 9 yrs) served as controls. Levels of plasma
      HNE bound to alpha1-antitrypsin (pHNE-alpha1AT) were measured by ELISA. The
      presence of HNE in the temporal artery wall of 7 TA and 7 non-TA patients was
      evaluated immunohistochemically. RESULTS: Age, neutrophil counts, and erythrocyte
      sedimentation rates were similar in TA and non-TA patients. The mean pHNE
      alpha1AT concentration in the TA group (84 +/- 20 microg/l) was significantly
      higher (p < 0.001) than in the non-TA group (51 +/- 26 microg/l) or in healthy
      controls (52 +/- 23 microg/l). The diagnostic sensitivity of pHNE-alpha1AT > 50
      microg/l was 100%. Immunohistochemistry detected no HNE within the temporal
      artery wall of any patient. CONCLUSION: High levels of pHNE-alpha1AT were
      associated with TA. Our preliminary results indicate this could be a diagnostic
      marker for TA. Further studies are needed to confirm its reliability. Because HNE
      was not detected locally, no conclusions can be drawn as to its pathogenic role
      in TA.

PMID- 9558174
TI  - An open study of pamidronate in the treatment of refractory ankylosing
      spondylitis.
AB  - OBJECTIVE: Bisphosphonates inhibit the development of delayed type
      hypersensitivity chronic inflammation and suppress inflammation and
      cartilage/bone erosion in diverse murine arthritis models. We evaluated
      antiinflammatory properties of the bisphosphonate pamidronate in patients with
      ankylosing spondylitis (AS) refractory to nonsteroidal antiinflammatory drugs.
      METHODS: Patients included 14 men and 2 women. The first group of 8 patients
      (Group 1) received pamidronate as a 30 mg intravenous infusion once a month for 3
      months, followed by a 60 mg dose once a month for an additional 3 months. Eight
      additional patients (Group 2) received only the 60 mg dose once a month for 3
      months. Clinical assessments included the BASDAI (Bath AS Disease Activity
      Index), BASFI (Functional Index), and BASMI (Metrology Index), and laboratory
      assessments hemoglobin and erythrocyte sedimentation rate (ESR) at baseline and
      one month after final 60 mg dose of pamidronate. Mean BASDAI score at study entry
      was 6.7 for both groups. RESULTS: A significant improvement was observed in
      disease activity score in Group 1 after 6 monthly infusions of pamidronate (mean
      BASDAI 4.21; p = 0.03), in the BASMI score (p = 0.01), and the ESR (p = 0.009). A
      significant improvement in the BASMI was noted in Group 2 patients (p = 0.007)
      after 3 monthly infusions of pamidronate, but not in the BASDAI score (mean 5.01;
      p = 0.07) or the ESR (p = 0.12). CONCLUSION: Preliminary data suggest pamidronate
      may possess antiinflammatory activity in patients with AS, particularly with
      prolonged administration; this agent deserves further evaluation in a controlled
      trial.

PMID- 9558172
TI  - Prevalence and characterization of novel pANCA, antibodies to the high mobility
      group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic
      diseases.
AB  - OBJECTIVE: To determine the immunodiagnostic value of antibodies to the high
      mobility group non-histone chromosomal proteins HMG1 and HMG2, which have been
      identified as novel target antigens of perinuclear antineutrophil cytoplasmic
      antibodies (pANCA), in sera from patients with systemic rheumatic diseases.
      METHODS: Anti-HMG1 or HMG2 antibody was assayed by ELISA and Western blotting in
      sera from patients with systemic rheumatic diseases. These antibodies were
      analyzed for the relationship with pANCA detected by indirect immunofluorescence
      in these diseases, and with clinical features in rheumatoid arthritis (RA) and
      systemic lupus erythematosus (SLE). RESULTS: Anti-HMG1 or HMG2 antibody was
      frequently detected in sera from patients with RA (48%), SLE (45%), Sjogren's
      syndrome (SS) (44%), and systemic sclerosis (SSc) (41%). In these diseases, anti
      HMG1 antibody was detected more frequently than anti-HMG2 antibody. In sera from
      patients with RA, the positivity for anti-HMG1 and HMG2 antibodies was
      significantly correlated with the positivity for pANCA (p < 0.0001). Anti
      HMG1/HMG2 antibodies were associated with some disease activity variables, e.g.,
      erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, joint
      score and hand grip strength in RA, and CH50, C3, C4, and IgG in SLE. CONCLUSION:
      Anti-HMG1/HMG2 antibodies are detected commonly in systemic rheumatic diseases,
      particularly in RA, SLE, SS, and SSc. HMGI and HMG2 seem to be the significant
      target antigens of pANCA in RA. These antibodies are significantly associated
      with disease activity indices in RA and SLE.

PMID- 9558175
TI  - Increased frequency of Sjogren's syndrome in patients with spondyloarthropathy.
AB  - OBJECTIVE: To determine the prevalence of sicca symptoms and Sjogren's syndrome
      (SS) in spondyloarthropathy (SpA) patients with ankylosing spondylitis (AS) and
      undifferentiated SpA (uSpA). METHODS: Patients with SpA with inflammatory back
      pain and/or peripheral arthritis presenting to the university outpatient clinic
      were diagnosed as AS (n = 40) and uSpA (n = 65) according to established
      criteria. Patients with SpA with sicca symptoms and/or positive antinuclear
      antibody (ANA) were investigated for SS by minor salivary gland biopsy and/or
      sialography. To assess sicca symptoms in this cohort systematically we mailed a
      validated questionnaire with 6 questions on dryness of eyes and mouth to all 105
      SpA patients and 150 healthy controls, a positive answer to > or = 3 questions
      was taken as suggestive of SS. There was no significant difference in baseline
      characteristics between patients and controls. RESULTS: In 8/105 SpA patients (5
      uSpA, 3 AS; 6 female, 2 male) SS diagnosis by the European criteria indicated a
      frequency of 7.6%. Of 105 SpA patients, 12 were ANA+ (11.4%), of whom 7 had SS;
      thus, ANA were detected in 7/8 SpA patients with SS (88%). Of the 84 SpA patients
      responding to the questionnaire (80%), 10 gave a positive answer to > or = 3
      questions (11.9%) compared to 2 of 131 (1.5%) controls (87.3%) (odds ratio = 8.7,
      95% CI 2.3-32.5, p < 0.01). CONCLUSION: The data suggest increased prevalence of
      sicca symptoms and SS in SpA patients with AS and uSpA. The occurrence of a
      secondary SS in a variety of inflammatory diseases suggests that salivary gland
      involvement in these conditions results from as yet unidentified shared
      pathogenic mechanisms resulting in nonspecific inflammation in this location.

PMID- 9558176
TI  - Musculoskeletal surgery in psoriatic arthritis.
AB  - OBJECTIVE: To determine the probability that patients with psoriatic arthritis
      (PsA) will require musculoskeletal surgery. To identify factors predictive of
      surgery in patients with PsA. To determine the clinical outcome of patients with
      PsA who underwent surgery compared to patients who did not. METHODS: The database
      of the Psoriatic Arthritis Clinic was searched to identify individuals who had
      undergone musculoskeletal surgery. Biological and clinical data such as
      erythrocyte sedimentation rate (ESR), rheumatoid factor, clinical pattern, nail
      changes, functional class, number of inflamed joints, and radiological damage, as
      well as health scores such as Arthritis Impact Measurement Scale 2 (AIMS-2), SF
      36, and Health Assessment Questionnaire (HAQ) were available for these patients.
      Patients who had surgery were compared to those who did not. RESULTS: Out of 444
      patients with confirmed PsA, 31 had musculoskeletal surgery (6.98%). This
      probability increased with the duration of PsA. Surgery patients had their first
      operation at an average of 13.9 years (range 1-46) after onset of joint disease.
      Age at onset of PsA, clinical pattern, constancy of clinical pattern over time,
      rheumatoid factor, functional class, symmetry, nail changes, and the time
      separating the onset of skin disease and the onset of joint disease were not
      significantly different at the 0.05 confidence level. Patients who had surgery
      had significantly more radiological damage (p < 0.001) and more actively inflamed
      joints (p < 0.02) at first assessment than patients who did not. AIMS2, SF-36,
      and HAQ scores at final review were not statistically different across both
      groups. CONCLUSION: In our patients the probability of having musculoskeletal
      surgery for PsA was 7%. It increased with disease duration. Patients had their
      first surgery after an average of 13 years. The number of actively inflamed
      joints and the extent of radiological damage at first assessment were highly
      predictive of subsequent surgery: patients with the highest numbers of severely
      affected joints, both clinically and radiologically, were more likely to have
      surgery. "Baseline characteristics" such as ESR, rheumatoid factor, functional
      class, clinical pattern, nail changes, and symmetry were not predictive of
      subsequent orthopedic surgery.

PMID- 9558177
TI  - HLA markers and progression in psoriatic arthritis.
AB  - OBJECTIVE: To investigate whether the addition of all serologically defined HLA
      antigens to a baseline model further influences the predisposition to disease
      progression in psoriatic arthritis (PsA). METHODS: Patients with PsA followed
      prospectively over 19 years were studied. Clinical and laboratory assessments of
      both active inflammation and clinical damage were performed at 6 month intervals
      according to a standard protocol. Progression of damage was defined as transition
      to higher damage states defined by the number of damaged joints. A model that
      provides estimates of the ratio of transition rates for an individual with the
      antigen versus one without, and examines the antigen effect on each of the 3
      transition rates, was used. HLA antigens were examined in groups by loci under
      the assumption of common effects across transitions when added to the basic
      model. The significance levels were examined in comparison with Bonferroni type
      corrections. Likelihood ratio chi-squared statistics were used as a basis for the
      significance levels. In total, 292 patients with PsA were included in the study.
      RESULTS: Only HLA-B22 was added to the original model, which includes HLA-B39,
      providing risk for progression in early stages, HLA-B27 in the presence of HLA
      DR7 providing risk for progression through all states, and DQw3 providing
      increased risk in the absence of DR7, while in the presence of DR7 it provides
      "protection." HLA-B22 provides protection from disease progression through all
      states. CONCLUSION: This study extends our report that HLA antigens serve as
      markers for disease progression in PsA.

PMID- 9558178
TI  - Synovial Chlamydia trachomatis in patients with reactive arthritis/Reiter's
      syndrome are viable but show aberrant gene expression.
AB  - OBJECTIVE: We used reverse transcription-polymerase chain reaction (RT-PCR)
      assays to assess expression of genes from Chlamydia trachomatis in synovial
      tissues of patients with reactive arthritis (ReA)/Reiter's syndrome (RS) to
      determine viability/metabolic activity of the bacterium in joints of infected
      patients. METHODS: Synovial biopsies were obtained from 18 patients with ReA, RS,
      or other arthritides; nucleic acids from 16 samples were PCR positive for
      chlamydial chromosomal DNA. RT-PCR assays targeting primary transcripts from C.
      trachomatis rRNA operons, and mRNA from the bacterial omp1, hsp60, glyQS, and r
      protein S5 and L5 genes, were used to characterize viability/metabolic activity.
      Host actin mRNA was assessed as control in each sample preparation. RESULTS: RT
      PCR of host cell actin mRNA in the 18 patient samples confirmed the quality of
      all RNA preparations. RNA from 14/16 PCR positive samples was positive by RT-PCR
      for chlamydial rRNA primary transcripts. Each of these same 14 samples was also
      RT-PCR positive in assays targeting glyQS, r-protein S5 and L5, and hsp60 mRNA.
      However, none of the 14 samples showing chlamydial rRNA and mRNA was positive for
      omp1 transcripts. CONCLUSION: Synovial chlamydia are viable/metabolically active,
      since primary rRNA transcripts and mRNA from chlamydial genes specifying
      components of the bacterial protein synthetic system were present in most patient
      samples assayed. Expression of omp1, encoding the major outer membrane protein,
      is strongly attenuated in persistently infecting synovial chlamydia, while that
      of hsp60, specifying a highly immunogenic heat shock protein of the organism, is
      not downregulated.

PMID- 9558179
TI  - Antibodies to Klebsiella pneumoniae in Dutch patients with ankylosing spondylitis
      and acute anterior uveitis and to Proteus mirabilis in rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether the association between increased humoral
      reactivity against Klebsiella and HLA-B27 associated diseases could be confirmed
      in Dutch patients with ankylosing spondylitis (AS) and acute anterior uveitis
      (AAU). METHODS: Under coded conditions sera from Dutch patients with AS, AAU, and
      rheumatoid arthritis (RA) and from HLA-B27 positive and negative healthy controls
      were studied for IgA anti-Klebsiella (K54) and IgG anti-Proteus antibodies with
      the indirect immunofluorescence assay on whole bacteria fixed in suspension with
      paraformaldehyde. Each group consisted of at least 17 sera. RESULTS: IgA anti
      Klebsiella antibody titers were elevated in AS and HLA-B27 negative AAU compared
      to the HLA-B27 positive and negative controls or patients with active RA (p <
      0.001). Furthermore, patients with active RA had elevated levels of IgG
      antibodies against P. mirabilis compared to every other test or control group (p
      < 0.001). There was no significant difference between the AS and RA patients in
      terms of serum C-reactive protein levels, although these were significantly
      elevated in both compared to healthy controls (p < 0.001), suggesting that the
      antibody elevations were not due to a nonspecific inflammatory effect. The same
      sera were blindly tested with negative results by 2 other centers. The
      discrepancies are probably the result of differences in the methods used.
      CONCLUSION: Our data support the hypothesis that Klebsiella are involved in the
      pathogenesis of AS and AAU and that the same might be true for Proteus in RA.

PMID- 9558180
TI  - Polyarthritis and periostitis induced by Escherichia coli. Lipopolysaccharide
      injection in young male hamsters.
AB  - OBJECTIVE: To describe the clinicopathological manifestations of
      lipopolysaccharide (LPS) induced arthritis in the hamster and to compare its time
      of onset, duration, and severity with other forms of experimentally induced
      arthritis. METHODS: A preparation containing 30 microg LPS from Escherichia coli
      was injected subcutaneously for 5 to 21 days into young male hamsters
      (Mesocricetus auratus). Arthritis was quantified by measuring soft tissue
      swelling of affected joints with calipers. After decalcification, paraffin
      sections were cut and stained with hematoxylin and eosin, Giemsa, and azan. Acute
      phase reactant apolipoprotein serum amyloid A (apoSAA) levels were determined by
      ELISA. RESULTS: Symmetrical polyarthritis developed within 3 days and persisted
      for 14-21 days, provided the hamsters received daily LPS injections. Most
      prominent were lesions in the carpal-metacarpal joints of the front legs and in
      the tarsal-metatarsal joints of the hind legs. Animals in whom LPS injections
      were discontinued after 4 or 7 days recovered completely. Histological findings
      of exudative synovitis, periarticular soft tissue swelling, and juxtaarticular
      periostitis were associated with a sharp rise in serum titers of apoSAA.
      CONCLUSION: The unusually rapid onset of arthritis and periostitis in this
      experimental animal model suggests that its systemic manifestations were not
      mediated by a classical immune response, and may represent an "innate" response
      of targeted cells within the synovial membrane and periosteum to bacterial cell
      wall endotoxins.

PMID- 9558181
TI  - In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis
      factor-alpha systems in human osteoarthritic synovium and chondrocytes.
AB  - OBJECTIVE: To evaluate the in vitro effects of diacerhein, a new drug for the
      treatment of osteoarthritis (OA), and its active metabolite, rhein, on
      interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha)
      synthesis and expression in human OA synovial membrane, and on the IL-1beta and
      TNF-alpha receptors on human OA chondrocytes. METHODS: Levels of IL-1beta and TNF
      alpha were determined using specific ELISA in culture medium of human synovial
      membrane explants incubated in the presence of 1 microg/ml of lipopolysaccharide
      with or without therapeutic concentrations of diacerhein (1.4, 2.7, 5.4 x 10(-5)
      M) and rhein (1.7, 3.5, 7.0 x 10(-5) M). IL-1beta mRNA level was quantitated by
      Northern blotting. Using radioligand binding experiments, we determined the
      effects of these agents on the density and affinity of chondrocyte IL-1 and TNF
      receptors. RESULTS: IL-1beta synthesis was significantly inhibited by diacerhein
      and rhein, with maximum inhibition at 5.4 x 10(-5) M for diacerhein (p < 0.02)
      and 3.5 x 10(-5) M for rhein (p < 0.05). The effect of both agents on IL-1beta
      was found to be translational and/or post-translational, judging by the absence
      of effect on gene expression level. Both agents produced dose and time dependent
      decreases in the number of IL-1 receptors (IL-1R) on OA chondrocytes. This effect
      was mediated through a reduction in the level of the type I IL-1R as shown by
      experiments using a blocking monoclonal antibody against this receptor type. Both
      agents also markedly reduced the IL-1 induced synthesis and expression of
      stromelysin 1. Neither diacerhein nor rhein significantly affected the level of
      synthesis of TNF-alpha or the level of TNF-R. CONCLUSION: Diacerhein and rhein
      can effectively inhibit the synthesis of IL-1beta on human OA synovium, as well
      as the action of this cytokine at the cartilage level, by reducing the number of
      chondrocyte IL-1R. The effects of these agents seemed "selective" to the IL-1
      system.

PMID- 9558182
TI  - Gastric administration of recombinant 65 kDa heat shock protein delays the
      severity of type II collagen induced arthritis in mice.
AB  - OBJECTIVE: The 65 kDa heat shock protein (HSP) chaperonin is a highly conserved
      intracellular protein. HSP are involved in the pathogenesis of arthritis, but are
      not able to induce experimental arthritis. T cell clones recognizing the 180-188
      amino acid sequence of 65 kDa HSP are present in inflamed synovium of both
      adjuvant arthritis and rheumatoid arthritis (RA). Oral administration of bovine
      collagen II or co-chaperonin 10 kDa HSP has been shown to induce an immune
      tolerance state to collagen induced arthritis (CIA). We investigate the effect of
      oral gavage with 65 kDa HSP on CIA. METHODS: We immunized 6-8-week-old DBA1 male
      mice with bovine type II collagen. A group of 25 mice were given oral recombinant
      mycobacterial 65 kDa HSP before immunization (30 microg in 200 microl phosphate
      buffered saline (PBS) at Days -7, -5, -2) while PBS alone was administered in 27
      controls. A 3rd group was fed 65 kDa HSP according to the same protocol but was
      not immunized with collagen II (n = 8). The clinical arthritis score was recorded
      3 times/week until Day 60. Antibodies to collagen II were determined by ELISA.
      RESULTS: The incidence of arthritis was comparable in the 2 groups (72 vs 70%).
      The onset of arthritis was not delayed in mice fed HSP. However, the severity of
      arthritis was lower 10 days after arthritis onset in animals fed 65 kDa HSP
      (clinical score 1.83 +/- 0.79 vs 2.74 +/- 1.1; p < 0.0001). No animals in Group 3
      had arthritis. Serum IgG anti-type II collagen levels were decreased in HSP
      treated mice (optical density 0.33 +/- 0.21 vs 0.46 +/- 0.21; p < 0.0001).
      However, the ratio of IgG1/IgG2a antitype II collagen antibody response remained
      unchanged in the mice fed 65 kDa HSP. CONCLUSION: These results suggest that oral
      administration of 65 kDa HSP may diminish collagen induced arthritis.

PMID- 9558183
TI  - Ambulatory activity as an objective and quantifiable measure of nonsteroidal
      therapy.
AB  - OBJECTIVE: To quantify any increase in short term spontaneous ambulatory activity
      resulting from the use of nonsteroidal antiinflammatory drugs (NSAID) in patients
      with rheumatoid arthritis (RA). METHODS: Double blind placebo controlled
      crossover study of 8 women with RA using conventional assessments and the Numact
      activity monitor. RESULTS: Patients' ambulatory activity was 50% greater during
      NSAID treatment compared to placebo treatment. Effect size calculated at 0.62,
      suggesting good sensitivity to change. The increased activity occurred late
      morning. CONCLUSION: Spontaneous ambulatory activity is an objective and relevant
      measure of disability.

PMID- 9558184
TI  - A randomized double blind trial of verbal NSAID education compared to verbal and
      written education.
AB  - OBJECTIVE: We performed a double blind randomized controlled trial to investigate
      whether patients taking nonsteroidal antiinflammatory drugs (NSAID) knew more
      about these drugs at followup depending on whether they were randomized to
      receiving or not receiving an NSAID information sheet. The patients were unaware
      they were in a study. METHODS: All patients received verbal education on the side
      effects of NSAID that was standardized and always given by the same
      rheumatologist. Thirty patients randomly received an NSAID information sheet and
      26 patients did not. At next clinic followup, after reading a letter of
      explanation about the study and signing a consent form, patients completed a
      questionnaire asking about their knowledge of NSAID. RESULTS: Outcome variables
      assessed within the questionnaire included whether NSAID : (1) can decrease
      inflammation; (2) help with pain; (3) cause stomach upset and bleeding in the
      bowels. None of these variables were statistically significant. The only variable
      that was statistically significantly different between the groups was their
      report of whether they had received an information sheet about NSAID (p<0.00004).
      A greater proportion of patients who received the NSAID information sheet
      correctly reported they had received one compared to those who had not received
      one and who said they had not received one (85% in the former group, 70% in the
      latter group). The group who received the NSAID information sheet were more apt
      to say that NSAID can help with their pain (odds ratio 6.1, p<0.05). Education
      level was positively correlated with knowledge (p<0.04). However, level of
      education explained only 11% of the variance in overall knowledge scores (r=0.34)
      among all patients. CONCLUSION: An information sheet may not add educational
      value over verbal information by a physician in a clinic setting.

PMID- 9558185
TI  - Paleopathology in osseous remains from the 16th century. A survey of rheumatic
      diseases.
AB  - OBJECTIVE: To describe the rheumatic conditions found in skeletal remains of
      Amerindian ancestry disinterred from a 16th century Mexican cemetery. METHODS: A
      physical anthropologist and 2 rheumatologists surveyed the recovered skeletal
      remains. RESULTS: We examined the skeletal remains of 443 subjects. We found 19
      cases of Pott's disease, 17 of osteoarthrosis in various anatomical locations, 2
      spondyloarthropathies, probably ankylosing spondylitis or diffuse idiopathic
      skeletal hyperostosis, one probable septic arthritis in the stemoclavicular
      joint, and 2 compression fractures of the spine. We found no cases of gout or
      rheumatoid arthritis. CONCLUSION: This is the first report on the presence of
      rheumatic conditions in colonial Mexico. Studying the remains of these
      populations can provide useful information about the origin and evolution of
      different rheumatic conditions.

PMID- 9558186
TI  - Juvenile rheumatoid arthritis in a Canadian First Nations (aboriginal)
      population: onset subtypes and HLA associations.
AB  - OBJECTIVE: To determine onset subtypes and HLA associations of juvenile
      rheumatoid arthritis (JRA) in a First Nations (aboriginal) population; to
      determine whether population frequencies of HLA antigens may explain the
      distribution of subtypes of JRA in this population. METHODS: All patients were
      children from Manitoba and Northwestern Ontario seen in a single pediatric
      rheumatology clinic between 1975 and 1996. Patients were identified from a clinic
      registry. Controls were adults of Algonkian Cree and Ojibway heritage. Class I
      and II major histocompatibility (HLA) typing was performed for First Nations
      patients and controls. RESULTS: There were a total of 74 First Nations patients
      with JRA. The relative frequency of rheumatoid factor (RF) positive polyarticular
      JRA was higher and that of pauciarticular JRA was lower in First Nations compared
      with Caucasian patients (42 versus 3% and 22 versus 58%, respectively; p =
      0.00000). HLA-DRB1*04 (63%), 08 (43%), and 1402 (25%) were the most common DRB1
      antigens among controls. The main subtypes of DRB1*04 were 0404 (33% of controls)
      and 0407 (23%). HLA typing was performed for 39 First Nations patients; 27 were
      Cree or Ojibway, 4 were from other tribes, and 8 were part First Nations. Among
      Cree and Ojibway, 59% of controls and 63% of patients with RF positive
      polyarticular JRA (n = 16) had HLA-DRB1 antigens bearing the rheumatoid arthritis
      (RA) shared epitope (OR 1.16, 95% CI: 0.38, 3.48). The OR for polyarticular RF
      positive JRA in those with DRB1*0802 and 0901 were 0.15, 95% CI: 0.02; and 1.24
      and 5.83, 95% CI: 1.58, 28.38, respectively. CONCLUSION: There was a high
      frequency of the RA shared epitope represented by both HLA-DRB1*0404 and 1402 in
      this Algonkian population. This high frequency may explain the high frequency of
      RF positive polyarticular JRA. DRB1*0802 may be protective, whereas DRB1*0901 may
      increase the risk for this subtype of JRA.

PMID- 9558187
TI  - Cyclosporine in the treatment of an unusual case of juvenile systemic sclerosis.
AB  - We describe a child who initially presented with juvenile dermatomyositis (JDM).
      Four years after the complete remission of JDM she developed systemic sclerosis
      without internal organ involvement. She was unresponsive to a combination of
      systemic corticosteroid therapy and pencillamine. The institution of cyclosporine
      induced a complete remission.

PMID- 9558188
TI  - A case of multicentric reticulohistiocytosis in a 6-year-old child.
AB  - Multicentric reticulohistiocytosis (MR) is a rare disease in which an
      infiltration of histiocytic cells causes destructive polyarthritis and
      characteristic cutaneous lesions. It predominantly affects women between the ages
      of 40 and 50 years. Effective treatment has not been well established. We
      describe a case diagnosed in a 6-year-old girl. This is the youngest patient with
      MR reported to date.

PMID- 9558189
TI  - Antinuclear antibody negative systemic lupus erythematosus presenting as
      bilateral facial paralysis.
AB  - Cranial neuropathy, and particularly facial palsy, is a rare occurrence in
      patients with systemic lupus erythematosus (SLE). We describe a 16-year-old
      female who developed bilateral facial palsy concomitant with cutaneous bullous
      eruption, alopecia, mucosal ulcers, arthritis, lymphadenopathy, parotid
      enlargement, and proteinuria. The lack of positive antinuclear antibody (ANA) at
      presentation obscured the diagnosis. Her followup course clarified the diagnosis
      of SLE. We believe this is the first report of ANA negative SLE presenting as
      bilateral facial palsy.

PMID- 9558190
TI  - Corticosteroids and systemic lupus erythematosus pancreatitis: a case series.
AB  - OBJECTIVE: To determine whether (1) corticosteroids cause pancreatitis in
      patients with systemic lupus erythematosus (SLE); (2) SLE pancreatitis occurs in
      the setting of a generalized SLE flare; and (3) corticosteroids can be used to
      treat SLE pancreatitis. METHODS: A total of 8 patients over a 10 year period with
      pancreatitis and SLE were identified retrospectively from a hospital database at
      the University of California San Diego Medical Center. RESULTS: All 8 patients
      received therapeutic doses of corticosteroids as part of their treatment for SLE
      and pancreatitis. All patients manifested both clinical and biochemical
      resolution of their pancreatitis with the administration of corticosteroids. No
      patient in our study experienced immediate complications related to
      corticosteroids. Only 2 of the 8 patients manifested active concurrent systemic
      disease related to the SLE. CONCLUSION: Corticosteroids do not cause pancreatitis
      in patients with SLE, and they should be administered during episodes of acute
      pancreatitis if clinically necessary. Pancreatitis does not tend to occur in the
      setting of a generalized SLE flare.

PMID- 9558191
TI  - Unusual coronary artery ectasia and stenosis in a patient with systemic lupus
      erythematosus and acute myocardial infarction.
AB  - Acute myocardial infarction is an important and sometimes fatal complication of
      systemic lupus erythematosus (SLE). We describe a case of acute myocardial
      infarction in a 23-year-old woman with SLE. Angiography revealed coronary ectasia
      in the left main and proximal circumflex coronary arteries, as well as a stenotic
      lesion in the left anterior descending artery. The possible pathophysiology is
      discussed.

PMID- 9558192
TI  - Catastrophic antiphospholipid antibody syndrome in primary systemic sclerosis.
AB  - We describe the first case of catastrophic antiphospholipid antibody syndrome
      (APS) in a patient with progressive systemic sclerosis (SSc). After initial
      presentation with digital gangrene the patient developed rapidly progressive
      multiorgan failure and died within 19 hours. Postmortem examination revealed
      extensive multiorgan arterial microthrombi of days' to months' duration. This
      suggests that a subclinical state of thrombosis existed before onset of
      catastrophic APS. Given the poor prognosis of established catastrophic APS there
      is a need for a means to detect subclinical thrombosis and treat "at risk"
      patients before clinically apparent thrombosis occurs.

PMID- 9558193
TI  - Arterial obliteration in POEMS syndrome: possible role of vascular endothelial
      growth factor.
AB  - Acute arterial obliteration is a newly acknowledged manifestation of the POEMS
      syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
      endocrinopathy, M protein, skin changes), in which overproduction of
      proinflammatory cytokines has been implicated. We describe a case in which serum
      levels of proinflammatory cytokines were normal or slightly raised. In contrast,
      vascular endothelial growth factor (VEGF) was greatly increased. This angiogenic
      and vascular permeability factor is involved in the development of atheromatous
      and thrombotic lesions and may be responsible for the arterial complications of
      the disorder.

PMID- 9558194
TI  - Refractory hyperglycemia complicating an evolving connective tissue disease:
      response to cyclosporine.
AB  - A 33-year-old woman with longstanding rheumatoid arthritis and Sjogren's syndrome
      developed type B insulin resistance (diabetes mellitus due to anti-insulin
      receptor antibodies) simultaneous with the evolution of her rheumatic disease to
      mixed connective tissue disease. Cyclosporine therapy induced a remission of
      receptor antibody mediated insulin resistance and controlled clinical
      manifestations of her systemic lupus erythematosus and dermatomyositis, but had
      no effect on the sclerodermatous features of her illness.

PMID- 9558195
TI  - The pyramids of rheumatoid arthritis.

PMID- 9558196
TI  - Genotyping HLA-B27 in spondyloarthropathies.

PMID- 9558197
TI  - Assessment of sexual function in patients with rheumatic disorders.

PMID- 9558198
TI  - Giant cell (temporal) arteritis and secondary amyloid: a matter of disease
      duration?

PMID- 9558199
TI  - A case of empty sella after steroid pulse therapy for nephrotic syndrome.

PMID- 9558200
TI  - Orthostatic sympathetic derangement of baroreflex in patients with fibromyalgia.

PMID- 9558201
TI  - Antinuclear antibody negative lupus associated with dystrophic calcification.

PMID- 9558202
TI  - Septic arthritis caused by Neisseria sicca.

PMID- 9558204
TI  - Risk Assessment for Neurobehavioral Toxicity

PMID- 9558203
TI  - First report of giant cell arteritis--in the Talmud.

PMID- 9558229
TI  - preface

PMID- 9558274
TI  - A new source of cells contributing to the developing gastrointestinal tract
      demonstrated in chick embryos.
AB  - BACKGROUND & AIMS: Smooth muscle cells in the walls of the gastrointestinal tract
      are thought to derive solely from mesoderm surrounding the primitive gut. A
      population of neuroepithelial cells has recently been shown to migrate from the
      ventral part of the neural tube in the region joined by the vagus nerve. We
      sought to determine if these cells contributed to the development of the stomach
      and intestine. METHODS: Cells of the ventral hindbrain of chick embryos were
      tagged by replication-deficient retroviral vectors containing the lacZ gene,
      providing a permanent label that is transmitted without dilution as the cells
      divide. Embryos were processed for detection of labeled cells. Specific markers
      were used to determine differentiation of progeny in the gastrointestinal tract.
      RESULTS: Cells labeled in the ventral neural tube migrate in association with the
      vagus nerve. Labeled cells are found in the intestine and stomach after time for
      further migration and differentiation. Using a specific marker, they were clearly
      identified as smooth muscle cells. CONCLUSIONS: Some of the smooth muscle cells
      of the gastrointestinal tract are derived from precursor cells that originate in
      the ventral part of the hindbrain neural tube. Their developmental importance and
      functional significance remain to be determined.

PMID- 9558273
TI  - Chemoprevention of spontaneous intestinal adenomas in the adenomatous polyposis
      coli Min mouse model with aspirin.
AB  - BACKGROUND & AIMS: Colorectal cancer is a significant source of morbidity and
      mortality in the United States and other Western countries. Epidemiological and
      experimental data indicate that regular use of aspirin reduces colon cancer risk.
      This study was designed to determine if aspirin would significantly inhibit
      gastrointestinal tumor formation in a mouse model of familial adenomatous
      polyposis. METHODS: Six-week-old male and female C57BL/6J +/+ (control) and
      C57BL/6J ApcMin/+ (Min) mice were fed either a control AIN-76A diet or one
      supplemented with 250 or 500 parts per million (ppm) aspirin (n = 6 per group)
      for 7 weeks. RESULTS: All of the Min mice, but no control mice, developed
      gastrointestinal tumors. Aspirin significantly reduced tumor multiplicity (number
      of tumors per mouse) in the small intestine, but not the colon, from an average
      of 35.8 tumors per mouse (control diet) to 16 and 18.5 tumors per mouse with 250
      and 500 ppm aspirin, respectively. Total tumor load (sum of tumor diameters per
      mouse) was also significantly reduced, from 93.2 mm in total diameter to 40. 4
      and 45.0 mm with 250 and 500 ppm aspirin, respectively. Results were not
      significantly different because of sex or aspirin dose. CONCLUSIONS: High doses
      of aspirin are effective chemopreventive agents in a mouse model of spontaneous
      intestinal tumor formation.

PMID- 9558275
TI  - Intractable upper gastrointestinal ulceration due to aspirin in patients who have
      undergone surgery for peptic ulcer.
AB  - BACKGROUND & AIMS: Postsurgical ulcer recurrence is a challenging problem. The
      aim of this study was to define the role of aspirin in postsurgical ulcers.
      METHODS: We studied 30 patients with postsurgical ulcer and aspirin abuse.
      Preoperatively 13 had stenosis, 7 bleeding, and 7 perforation or penetration; 18
      had undergone vagotomy and 11 gastrectomy. RESULTS: Of 30 patients, 15 admitted
      long-term aspirin use (1-4 g/day), whereas 15 denied use but had positive
      salicylate blood levels (15.1 +/- 2.25 mg/100 mL; >1 mmol/L). Gastrin or gastric
      secretion was normal in the 24 patients tested. On follow-up, 3 (10%) healed
      after surgery (all stopped taking aspirin), whereas 27 continued and had new
      ulcers; 12 (44%) developed stenosis, and 6 (23%) developed bleeding. A second
      operation was required in 16 patients who had continued aspirin abuse, which was
      surreptitious in 10 (63%). Thirteen of these 16 had recurrent ulceration (7 [43%]
      with stenosis and 1 with bleeding); 1 died and 2 stopped taking aspirin and
      healed. A third operation was required in 8 patients. All had continued aspirin
      abuse (75% surreptitiously), and all again had relapses (3 with stenosis); 1
      underwent an unsuccessful fourth operation, and 3 died. CONCLUSIONS: With
      continued aspirin abuse, recurrent ulceration is the rule, and complications,
      especially stenosis, are common. Surreptitious aspirin abuse, if discovered, is a
      clear contraindication to elective ulcer surgery, because aspirin-abuse
      ulceration is incurable by gastric surgery.

PMID- 9558276
TI  - Cost analysis of alternative approaches to colorectal screening in familial
      adenomatous polyposis.
AB  - BACKGROUND & AIMS: The commercial availability of gene testing for familial
      adenomatous polyposis (FAP) represents an important advance in screening for
      inherited colon cancer. We investigated the financial impact of this diagnostic
      tool on colorectal screening for FAP. METHODS: Decision analysis was used to
      compare per-person costs with third-party payers of three colorectal screening
      strategies used to diagnose FAP in at-risk persons. The strategies included
      conventional serial flexible sigmoidoscopy and two different APC gene testing
      approaches. RESULTS: For 1 at-risk relative who begins screening at age 12 years,
      average screening costs are $2625 when genotyping the proband first, $2674 when
      genotyping the at-risk relative first, and $3208 for conventional sigmoidoscopy.
      The cost advantage of genotyping increases as the pedigree size increases. For a
      pedigree of 5 at-risk relatives, sigmoidoscopy would have to cost less than
      $85.60 (professional plus facility fee) for conventional screening to compete
      with genotyping. The cost advantage of genotyping is diminished for at-risk
      relatives who begin FAP screening at older ages. CONCLUSIONS: The choice of least
      expensive FAP screening strategy depends on the cost of flexible sigmoidoscopy,
      patient age when screening starts, and pedigree size. Genotyping can
      substantially reduce the cost of FAP screening and, when possible, should start
      with the proband.

PMID- 9558277
TI  - Curling of Curling's ulcer 

PMID- 9558278
TI  - Bone mineral density assessment in children with inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Children with inflammatory bowel disease (IBD) are at risk for
      osteoporosis because of undernutrition, delayed puberty, and prolonged
      corticosteroid use. The aim of this study was to compare bone mineral density
      (BMD) in children with IBD with that in normal children and to assess the effects
      of nutritional and hormonal factors and corticosteroid dosages on BMD. METHODS:
      One hundred sixty-two subjects (99 with IBD and 63 healthy sibling controls) were
      enrolled. Patients underwent anthropometric assessment, pubertal staging, bone
      age radiography, and BMD assessment by dual energy x-ray absorptiometry of the
      lumbar spine, femoral neck, and radius. Laboratory evaluations included serum
      calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, 1,25
      dihydroxyvitamin D, parathyroid hormone, osteocalcin, urinary N-telopeptides,
      albumin, insulin-like growth factor I, and testosterone or estradiol. Cumulative
      corticosteroid doses were calculated. RESULTS: BMD Z scores at the lumbar spine
      and femoral neck were lower in patients with IBD, and lower in those with Crohn's
      disease compared with those with ulcerative colitis. Low BMD persisted after
      correction for bone age in girls with Crohn's disease (lumbar spine, P = 0.004;
      femoral neck, P = 0.002). Cumulative corticosteroid dose was a significant
      predictor of reduced BMD. BMD did not correlate with measures of calcium
      homeostasis, except elevated serum phosphate and urine calcium levels in girls.
      CONCLUSIONS: Low BMD occurs in children with IBD (more in Crohn's disease than in
      ulcerative colitis), especially pubertal and postpubertal girls. Cumulative
      corticosteroid dose is a predictor of low BMD, but other factors in Crohn's
      disease remain undetermined.

PMID- 9558279
TI  - Tropomyosin isoforms in intestinal mucosa: production of autoantibodies to
      tropomyosin isoforms in ulcerative colitis.
AB  - BACKGROUND & AIMS: Autoantibodies against tropomyosins (TMs) have been reported
      in ulcerative colitis (UC). In this study the hTM isoforms (hTM1-5) present in
      intestinal epithelial cells and in smooth muscle were investigated, and the
      immunoreactivity against hTMs by immunoglobulin G (IgG) produced in vitro by
      colonic mucosal lymphocytes (LPMCs) from patients with UC, Crohn's disease (CD),
      and controls was examined. METHODS: TMs were extracted from colonic and jejunal
      epithelial cells and smooth muscle, and hTM isoforms were identified using
      isoform-specific monoclonal antibodies by enzyme-linked immunosorbent assay and
      transblot analysis. The immunoreactivity of IgG produced by colonic LPMCs was
      analyzed against the recombinant hTM isoforms. RESULTS: The major hTM isoforms
      present in colonic and jejunal epithelial cells are hTM5 and hTM4, whereas
      intestinal smooth muscle contains the hTM1-3 isoforms. The IgG synthesized in
      vitro by LPMCs from UC (n = 19) recognized hTM5 and hTM1, more significantly (P <
      0.04 to <0.001) when compared with CD (n = 12) and controls (n = 17). However,
      IgG produced by LPMCs from CD did not show such anti-hTM reactivity. Mucosal anti
      hTM IgG mainly belonged to the IgG1 subclass. CONCLUSIONS: Intestinal epithelial
      cells and smooth muscle have distinct hTM isoforms. Patients with UC, and not CD,
      show mucosal autoantibody response against hTM isoforms, particularly hTM5 and
      hTM1.

PMID- 9558280
TI  - Bismuth subsalicylate markedly decreases hydrogen sulfide release in the human
      colon.
AB  - BACKGROUND & AIMS: Hydrogen sulfide is one of the main malodorous compounds in
      human flatus. This toxic gas also has been implicated in the pathogenesis of
      ulcerative colitis. Therefore, a treatment that reduces colonic H2S levels could
      be clinically useful in the treatment of flatus odor and of ulcerative colitis.
      In this study the ability of bismuth subsalicylate, a compound that binds H2S, to
      reduce H2S release in the colon, was tested. METHODS: Homogenates made from human
      and rat feces were incubated with and without bismuth subsalicylate, and gas
      production was measured. Fecal samples from 10 healthy subjects were analyzed
      before and after ingestion of bismuth subsalicylate (524 mg four times a day) for
      3-7 days. RESULTS: Fecal homogenates showed a dose-dependent relationship between
      the concentration of bismuth subsalicylate and H2S release. Treatment of subjects
      with bismuth subsalicylate produced a >95% reduction in fecal H2S release.
      CONCLUSIONS: The ability of bismuth subsalicylate to dramatically reduce H2S
      could provide a clinically useful means of controlling fecal and/or flatus odor
      and of decreasing the putative injurious effects of H2S on the colonic mucosa.

PMID- 9558281
TI  - Inhibition of epidermal growth factor receptor kinase induces protease-dependent
      apoptosis in human colon cancer cells.
AB  - BACKGROUND & AIMS: The epidermal growth factor receptor (EGFR) is under
      investigation as a therapeutic target for cancers. Colon cancer cell lines are
      variably dependent on autocrine stimulation of EGFR. We therefore examined the
      effects of a selective EGFR tyrosine kinase inhibitor, PD 153035, on
      proliferation and survival of five colon cancer cell lines whose autonomous
      proliferation is either EGFR ligand dependent or EGFR ligand independent.
      METHODS: Effects of inhibitors were screened by MTS growth assays, [3H]thymidine
      incorporation, terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick-end labeling assay, fluorescence microscopy, immunoblotting,
      and in vitro protease assays. RESULTS: PD 153035 caused dose-dependent cytostasis
      (200 nmol/L to 1 micromol/L) and apoptosis (>10 micromol/L) in ligand-dependent
      cell lines and caused variable apoptosis (>10 micromol/L) but no cytostasis in
      ligand-independent cell lines. Apoptosis induced by 10 micromol/L PD 153035 was
      not associated with induction of p53 protein expression but was accompanied by
      activation of caspases that cleave poly(ADP-ribose) polymerase, lamin B1, and Bcl
      2. Inhibition of caspase 3-like protease activity by DEVD-fluoromethylketone
      significantly delayed the onset of PD 153035-induced apoptosis. CONCLUSIONS: The
      EGFR tyrosine kinase inhibitor PD 153035 induces cytostasis and caspase-dependent
      apoptosis in EGFR ligand-dependent colon cancer cell lines. These observations
      encourage further investigation of EGFR tyrosine kinase inhibitors for treatment
      of colorectal neoplasms.

PMID- 9558282
TI  - Short-chain fatty acids induce cell cycle inhibitors in colonocytes.
AB  - BACKGROUND & AIMS: We tested the hypothesis that short-chain organic acids in the
      colon derived from dietary pectin, wheat bran, and oat bran are protective
      against the development of colon cancer because they induce transforming growth
      factor (TGF)-beta1, which in turn inhibits cell growth by inducing cyclin
      directed kinase (cdk) inhibitors. METHODS: U4 human colon carcinoma cells
      differentiate into water- and salt-transporting columnar enterocytes and
      therefore model normal colonocytes. The composition and kinase activity of
      cdk/cyclin complexes were determined by immunoprecipitation and Western blotting
      studies in U4 cells treated in vitro with short-chain fatty acid (SCFA) mixtures
      that mimic the digestion products of wheat bran, oat bran, pectin, and cellulose
      (as control), which is largely unfermentable. RESULTS: Induction of the cdk
      inhibitors p21cip1 and p27kip1 by fiber-mimicking SCFA mixtures occurs much more
      rapidly and is many-fold greater than their induction by TGF-beta1. The SCFA
      mixtures most effective in causing growth inhibition and cdk inhibitor production
      mimicked those from wheat bran > oat bran > pectin. CONCLUSIONS: cdk inhibitor
      induction by SCFA mixtures is not mediated by TGF-beta1. The SCFA mixture
      mimicking digested wheat bran fiber was the most effective of all mixtures tested
      in inhibiting cell growth through induction of cdk inhibitors.

PMID- 9558284
TI  - Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced
      enteritis in mice.
AB  - BACKGROUND & AIMS: The pathogenesis of Clostridium difficile toxin A-induced
      intestinal inflammation is not completely understood. The aim of this study was
      to define the contribution of mast cells to the fluid secretion and neutrophil
      infiltration associated with toxin A-induced enteritis. METHODS: Fluid secretion
      and neutrophil infiltration in toxin A- or buffer-challenged ileal loops were
      assessed in normal, mast cell-deficient, and mast cell-deficient KitW/KitW-v mice
      that had undergone selective repair of their mast cell deficiency. The effect of
      a specific substance P-receptor antagonist was also studied. RESULTS: Intestinal
      fluid secretion and neutrophil recruitment were significantly diminished in mast
      cell-deficient KitW/KitW-v and mast cell-deficient MgfSl/MgfSl-d mice compared
      with the respective normal mice. Mast cell-reconstituted KitW/KitW-v mice showed
      responses similar to the normal congenic mice. Administration of a specific
      substance P-receptor antagonist (CP-96,345) reduced toxin A-induced intestinal
      fluid secretion and inhibited neutrophil infiltration in normal, mast cell
      deficient KitW/KitW-v, and mast cell-reconstituted KitW/KitW-v mice. CONCLUSIONS:
      C. difficile toxin A elicits intestinal fluid secretion and neutrophil
      infiltration by both mast cell-dependent and -independent pathways, and substance
      P participates in both pathways.

PMID- 9558283
TI  - Rotavirus infection of cultured intestinal epithelial cells induces secretion of
      CXC and CC chemokines.
AB  - BACKGROUND & AIMS: Rotaviruses are the major cause of pediatric gastroenteritis
      worldwide. The target cell of rotavirus infection is the mature enterocyte of the
      small intestine. Recently, intestinal epithelial cells have been shown to produce
      chemoattractant mediators in response to cytokine stimulation and bacterial
      infection, suggesting a potentially important role of epithelial cells in
      initiating immune responses. In this study, the production of chemokines by
      cultured intestinal epithelial cells after rotavirus infection was investigated.
      METHODS: Two human intestinal epithelial cell lines (HT29 and Caco-2) were
      infected with sucrose-purified rotavirus (strain SA114F) and assayed by reverse
      transcription polymerase chain reaction and enzyme-linked immunosorbent assay for
      chemokine expression. Virus-like particles and inactivated rotavirus were used to
      test the importance of viral attachment and replication. RESULTS: Increased
      messenger RNA expression and secretion of immunoreactive interleukin 8, growth
      related peptide alpha, and RANTES (regulated upon activation, normal T cell
      expressed and secreted) were detected in rotavirus-infected cells. Chemokine
      production was time and dose dependent and required viral replication.
      CONCLUSIONS: Rotavirus infection induces the expression of a subset of chemokines
      in intestinal epithelial cells. These data support the hypothesis that chemokine
      secretion by enterocytes may play a role in the initiation and modulation of the
      immune response to rotavirus infection.

PMID- 9558285
TI  - Regional differences in L-selectin expression in murine intestinal lymphocytes.
AB  - BACKGROUND & AIMS: The expression of the lymphocyte homing receptor and
      activation marker L-selectin is different in colon and small intestinal
      intraepithelial lymphocytes (IELs). In this study, the mechanism of this
      difference in L-selectin expression was investigated. METHODS: L-selectin
      expression on lymphocytes was measured by flow cytometry. L-selectin messenger
      RNA (mRNA) was detected by reverse-transcription polymerase chain reaction. L
      Selectin expression on peripheral lymphocytes was analyzed after incubation with
      cytokines, food and bacterial antigens, and homogenates of small and large bowel.
      RESULTS: L-selectin was expressed by none of the small intestinal IELs but by 30%
      of those in the colon and by 60% of splenocytes. mRNA for L-selectin was
      detectable in isolated lymphocytes of all three sites. L-Selectin was down
      regulated in colon IELs during colitis and up-regulated in small intestinal IELs
      after in vitro culture for 48 hours. Incubation of splenocytes with small
      intestinal homogenates led to a rapid down-regulation of L-selectin (1% vs. 60%
      untreated). Preincubation with a metalloproteinase inhibitor prevented L-selectin
      loss. CONCLUSIONS: The mechanism of the differential expression of L-selectin in
      mouse small intestine and colon appears to be an increased functional activity of
      a metalloproteinase (sheddase) in the small intestine compared with the colon.

PMID- 9558286
TI  - The inaccuracy of duplex ultrasonography in predicting patency of transjugular
      intrahepatic portosystemic shunts.
AB  - BACKGROUND & AIMS: A prospective double-blinded study with preset sonographic
      criteria has not been performed to assess the accuracy of duplex ultrasonography
      in determining the patency of transjugular intrahepatic portosystemic shunts
      (TIPS). The purpose of this study was to determine the sensitivity and
      specificity of duplex ultrasonography in predicting shunt malfunction using
      accepted preset sonographic criteria. METHODS: Sixty ultrasonographic and
      venographic follow-up comparisons were made on 38 cirrhotic patients who had
      undergone TIPS placement for variceal bleeding (n = 28) or intractable ascites (n
      = 10). Ultrasonographic results were analyzed by one of two board-certified
      ultrasonographers without knowledge of venographic findings. RESULTS: Of the 31
      occluded (n = 8) and stenotic (n = 23) shunts, ultrasonography accurately
      predicted a shunt malfunction (occlusion or stenosis) in only 11 studies and
      incorrectly predicted patency in 20. Compared with venography, ultrasonography
      had a sensitivity of 35% and a specificity of 83% in predicting TIPS stenosis or
      occlusion. CONCLUSIONS: These results suggest that duplex sonography is not a
      sensitive test in predicting the presence of a hemodynamically significant
      stenosis and that shunt status should be assessed by venography and direct portal
      pressure measurements until a more reliable and proven noninvasive
      ultrasonographic criterion is devised.

PMID- 9558287
TI  - "Salvage" transjugular intrahepatic portosystemic shunts: gastric fundal compared
      with esophageal variceal bleeding.
AB  - BACKGROUND & AIMS: The optimal emergency treatment for gastric fundal variceal
      bleeding is still unclear. In this study, the efficacy of transjugular
      intrahepatic portosystemic stent/shunt (TIPS) in patients with uncontrolled
      gastric fundal vs. esophageal variceal bleeding was compared. METHODS: One
      hundred twelve consecutive patients with uncontrolled variceal bleeding required
      emergency TIPS, 84 with esophageal varices (EV group) unresponsive to endoscopic
      and vasoconstrictor therapy and 28 with gastric fundal varices (GV group)
      unresponsive to vasoconstrictor therapy. Clinical and biochemical data were
      retrieved, and the two groups were compared. RESULTS: Variceal bleeding was
      controlled in all patients after TIPS except for 1 in each group. There were no
      significant differences between the two groups in terms of markers of disease
      severity, severity of bleeding, or portal hemodynamics. During a median follow-up
      period of 7 months, 20 in the EV group (24%) and 8 in the GV group (29%)
      developed clinical rebleeding. Most early rebleeding (within 7 days after TIPS)
      was related to esophageal ulceration secondary to previous sclerotherapy. Rates
      of mortality were similar in both groups. CONCLUSIONS: These results suggest that
      emergency TIPS is equally effective in the immediate short-term control of
      gastric fundal variceal bleeding compared with esophageal variceal bleeding.

PMID- 9558288
TI  - Interferon alfa therapy for chronic hepatitis B in children: a multinational
      randomized controlled trial.
AB  - BACKGROUND & AIMS: Treatment of chronic hepatitis B with interferon alfa is not
      approved in children. The aim of this study was to evaluate the safety and
      efficacy of interferon alfa (IFN-alpha) in children with chronic hepatitis B and
      increased transaminase levels. METHODS: Children were given either IFN-alpha2b (6
      megaunits/m2 thrice weekly for 24 weeks) or no treatment. Clearance of markers of
      viral replication was evaluated 24 weeks after therapy and after 48 weeks of
      observation in controls. RESULTS: Of 149 children enrolled, 144 were evaluable
      (70 treated and 74 controls). Serum hepatitis B e antigen and viral DNA became
      negative in 26% of treated children and 11% of controls (P < 0.05). Serum
      aminotransferase levels normalized and liver histology improved among responders.
      Hepatitis B surface antigen became undetectable in 10% of treated patients and 1%
      of controls. Female gender and interferon treatment were the only significant
      predictors of response. Ethnic origin, baseline aminotransferase level, initial
      DNA levels, and histology did not correlate with response. Most adverse reactions
      were mild or moderate, and dose was reduced in 24% of children. CONCLUSIONS: In
      children with chronic hepatitis B, INF-alpha promotes loss of viral replication
      markers and surface antigen and improves aminotransferases and histology.

PMID- 9558289
TI  - Heterogeneity of hemochromatosis in Italy.
AB  - BACKGROUND & AIMS: Patients with hemochromatosis show variable phenotype
      expression. We evaluated the frequency of hemochromatosis gene (HFE) mutations
      and the contribution of HFE genotype, ancestral haplotype, ethnic background, and
      additional factors (alcohol intake, hepatitis viruses, and beta-thalassemia
      trait) to the severity of iron overload in a large series of Italian patients
      with a hemochromatosis phenotype. METHODS: HFE genotype was studied in 188
      patients. Phenotype evaluation was available in 153 men and 20 women and was
      based mainly on iron removed. HFE genotype was determined by a polymerase chain
      reaction restriction assay and ancestral haplotype through D6S265 and D6S105
      microsatellite analysis. RESULTS: The frequency of C282Y homozygotes was 64%,
      with a decreasing gradient from north to south. C282Y homozygotes showed more
      severe iron overload than the other HFE genotypes. In the same group, ancestral
      haplotype was associated with a more severe phenotype. Additional factors may
      favor the development of a relatively mild hemochromatosis phenotype in patients
      nonhomozygous for the C282Y mutation. CONCLUSIONS: Hemochromatosis in Italy is a
      nonhomogenous disorder in which genetic and acquired factors are involved. In
      patients with a single or no HFE mutation, further studies will enable a
      differentiation between true genetic disorders and interactions between genetic
      and acquired factors.

PMID- 9558290
TI  - Expression of HLA-linked hemochromatosis in subjects homozygous or heterozygous
      for the C282Y mutation.
AB  - BACKGROUND & AIMS: In the absence of a genetic test, diagnostic criteria for
      hereditary hemochromatosis have been imprecise. The identification of the HFE
      gene and the C282Y mutation allow definition of expression of this disease and
      reassessment of diagnostic criteria. The aim of this study was to analyze the
      concordance between the genetic diagnosis and the previous clinical diagnosis in
      families with hemochromatosis. METHODS: Three hundred subjects were tested for
      the C282Y mutation and were grouped as homozygous, heterozygous, or homozygous
      normal. RESULTS: All adults previously diagnosed as homozygous or heterozygous
      for HLA-linked hereditary hemochromatosis carried at least one C282Y mutation.
      Two adolescents, previously thought to be homozygous, had no C282Y mutation. Of
      127 subjects homozygous for the mutation, 105 met criteria for diagnosis. Iron
      overload was not expressed in 6.7% of homozygous men and 32.7% of homozygous
      women. The iron indices in 8 of 171 subjects heterozygous for the C282Y mutation
      were within the range previously regarded as indicative of homozygosity. Seven of
      these 8 carried the H63D mutation. CONCLUSIONS: In Australia, 17.3% of subjects
      homozygous for the C282Y mutation do not express iron overload to meet current
      diagnostic criteria of hemochromatosis. In subjects heterozygous for the
      mutation, 4.8% have iron overload in the range previously diagnosed as
      homozygous. Nonexpression is common, particularly in women.

PMID- 9558291
TI  - Circulating xanthine oxidase and neutrophil activation during human liver
      transplantation.
AB  - BACKGROUND & AIMS: Oxygen free radicals, generated by xanthine oxidase (XO) and
      activated leukocytes, are involved in reperfusion injury in experimental liver
      transplantation. The roles of XO and neutrophil activation during reperfusion in
      clinical liver transplantation were studied. METHODS: In 10 patients undergoing
      liver transplantation, we assessed plasma concentrations of circulating XO by
      enzyme-linked immunosorbent assay (ELISA), the purine metabolites hypoxanthine,
      xanthine, and urate by high-performance liquid chromatography, lactoferrin by
      ELISA, and malondialdehyde fluorometrically up to 48 hours postoperatively.
      RESULTS: During reperfusion after portal vein declamping, elevated plasma
      concentrations of XO (52.1 ng/mL [range, 8.0-440.1]), hypoxanthine (81.62
      micromol/L [48.2-108.7]), xanthine (21.01 micromol/L [8.7-22.3]), and lactoferrin
      (532.6 ng/mL [370.4-1326.6]) were observed compared with the preoperative levels
      (0 ng/mL [0-12], 1.88 micromol/L [0.62-3.15], 0.95 micromol/L [0-0.41], and 164.3
      ng/mL [73.7-334.1], respectively; all P < 0.05). No changes occurred in urate or
      malondialdehyde. After portal vein declamping, XO, hypoxanthine, and xanthine
      levels were substantially greater in the hepatic than portal vein (all P < 0.05).
      Marginal transhepatic differences occurred in lactoferrin. CONCLUSIONS:
      Reperfusion during liver transplantation is associated with liberation of
      xanthine oxidase, hypoxanthine, and xanthine from the liver into the circulation.
      During reperfusion, intravascular neutrophil activation takes place in the
      hepatic circulation.

PMID- 9558292
TI  - Cholesterol saturation, not proteins or cholecystitis, is critical for crystal
      formation in human gallbladder bile.
AB  - BACKGROUND & AIMS: Biliary proteins are promoters of cholesterol crystallization
      in artificial model bile. However, their pathogenic importance for cholesterol
      precipitation in native gallbladder bile (GB) is uncertain. The aim of this study
      was to evaluate the significance of biliary lipids and proteins on cholesterol
      crystal detection time (ChCDT) of GB in patients with gallstones. METHODS: ChCDT
      and concentrations of lipids, albumin, mucins, aminopeptidase N, alpha1-acid
      glycoprotein, haptoglobin, and immunoglobulins (Igs) were measured in GB of 92
      patients, 52 of whom had cholesterol gallstones. RESULTS: ChCDT was markedly
      reduced in gallstone patients. Compared with patients without gallstones, they
      had a significant increase in cholesterol saturation and total protein, albumin,
      mucin, and IgG biliary concentrations. In univariate analysis, ChCDT of GB was
      significantly correlated with cholesterol saturation and total lipid, protein,
      Ig, aminopeptidase N, and alpha1-acid glycoprotein concentrations. However,
      stepwise logistic regression analysis showed that only cholesterol saturation
      independently correlated to ChCDT. Gallbladder inflammation correlated with the
      concentration of Igs, but subtraction of IgG from GB did not modify the ChCDT.
      CONCLUSIONS: Biliary cholesterol transport and saturation, but not proteins,
      appear critical for the cholesterol crystallization abnormality observed in
      native bile from patients with gallstones.

PMID- 9558293
TI  - Reduced plasma cholesterol and increased fecal sterol loss in multidrug
      resistance gene 2 P-glycoprotein-deficient mice.
AB  - BACKGROUND & AIMS: mdr2 P-glycoprotein (Pgp) deficiency in mice leads to the
      absence of biliary phospholipids and cholesterol in the presence of normal bile
      salt secretion. The aim of this study was to evaluate the importance of the
      biliary pathway in cholesterol homeostasis by determining the effects of mdr2 Pgp
      deficiency on hepatic and plasma lipid levels and cholesterol kinetics in chow
      fed mice. METHODS: Hepatic lipid content, enzyme activities, plasma lipoprotein
      levels, and fecal sterol excretion were measured in wild-type (+/+) and mdr2 Pgp
      deficient (-/-) mice. Cholesterol kinetics were determined using radiotracer
      techniques. RESULTS: No differences in hepatic lipid content were observed
      between (-/-) and (+/+) mice. Plasma high-density lipoprotein cholesterol and
      apolipoprotein A-I levels were strongly reduced in (-/-) mice compared with
      controls, whereas the apolipoprotein B contents of very-low-density lipoprotein
      and low-density lipoprotein were increased. Hepatic activity of 3-hydroxy-3
      methylglutaryl-coenzyme A reductase was threefold greater in (-/-) mice than in
      controls; however, compartmental analysis of plasma cholesterol decay showed no
      differences in cholesterol synthesis between (-/-) and (+/+) mice. A dual isotope
      approach for estimating cholesterol absorption yielded approximately 50% lower
      values in (-/-) mice than in controls. Surprisingly, (-/-) mice showed a fourfold
      increase in fecal neutral sterol secretion. CONCLUSIONS: This study unequivocally
      establishes the important direct role of biliary lipids in the regulation of
      plasma lipid levels in mice.

PMID- 9558295
TI  - Bumetanide-sensitive cell swelling mediates the inhibitory effect of ethanol on
      proteolysis in rat liver.
AB  - BACKGROUND & AIMS: Ethanol is known to inhibit proteolysis and to cause
      intracellular protein accumulation in the liver. The aim of this study was to
      investigate the mechanism underlying the antiproteolytic effect of ethanol.
      METHODS: The effects of ethanol on proteolysis and cell volume were assessed in
      the isolated perfused rat liver by established tracer techniques. RESULTS:
      Infusion of ethanol (20 mmol/L) led to an increase of the intracellular water
      space by 9.3% +/- 0.4% (n = 3), which was abolished by methylpyrazole and
      mimicked by acetaldehyde (5 mmol/L). Ethanol-induced cell swelling was completely
      abolished by bumetanide (5 micromol/L), an inhibitor of Na-K-2Cl cotransport.
      Ethanol (20 mmol/L) inhibited proteolysis by 18.6% +/- 2.0% (n = 4) in a
      colchicine-sensitive way. This antiproteolytic effect was quantitatively mimicked
      by equipotent hyposmotic hepatocyte swelling and by acetaldehyde. Ethanol-induced
      inhibition of proteolysis was abolished in the presence of methylpyrazole (100
      micromol/L), bumetanide (5 micromol/L), furosemide (100 micromol/L), and insulin
      (35 nmol/L), i.e., conditions that also prevented ethanol-induced cell swelling.
      CONCLUSIONS: Ethanol causes, via acetaldehyde, bumetanide-sensitive cell
      swelling, which in turn mediates the antiproteolytic effect of this alcohol. The
      data indicate the involvement of cell hydration changes in mediating metabolic
      ethanol effects and could suggest the activation of a putative Na-K-2Cl
      cotransport in liver by ethanol/acetaldehyde.

PMID- 9558294
TI  - Concanavalin A-induced liver cell damage: activation of intracellular pathways
      triggered by tumor necrosis factor in mice.
AB  - BACKGROUND & AIMS: Concanavalin A (con A) induces tumor necrosis factor (TNF)
      dependent hepatocyte apoptosis resembling immune-mediated fulminant hepatic
      failure in humans. Intracellular pathways originating at the TNF receptor are
      either linked to apoptosis, nuclear factor (NF)-kappaB translocation, or Jun
      kinase (JNK) activation. The aim of this study was to study TNF-dependent
      pathways after con A injection in vivo. METHODS: Con A, con A plus anti-TNF, and
      control buffer were injected into BALB/c mice. Immunofluorescence, Western blot,
      Northern blot, gel shift, Erk, and JNK activity and DNA fragmentation experiments
      were performed at different time points after injection. RESULTS: DNA
      fragmentation in hepatocytes was increased 4-24 hours after con A injection. JNK
      was activated maximally (>20-fold) directly after con A injection, whereas
      binding and nuclear translocation of NF-kappaB was maximal after 4 hours. All
      pathways were blocked by anti-TNF. JNK activation was specific because related
      ERK 1 + 2 were not activated after con A. High nuclear expression of c-Jun was
      already evident 1 hour after con A injection; however, in contrast to JNK, anti
      TNF treatment did not block c-Jun nuclear expression and DNA binding.
      CONCLUSIONS: In the con A model, activation of TNF-dependent pathways is
      associated with apoptosis of hepatocytes. Their modulation in vivo may have
      implications to develop new therapeutic strategies to prevent apoptosis.

PMID- 9558296
TI  - Pituitary adenylate cyclase-activating peptide stimulates rat pancreatic
      secretion via secretin and cholecystokinin releases.
AB  - BACKGROUND & AIMS: Pituitary adenylate cyclase-activating polypeptide (PACAP)
      stimulates protein and/or amylase secretion from isolated rat pancreatic acini.
      The effect of PACAP on pancreatic secretion in vivo and its mechanism of action
      were studied. METHODS: Rats were prepared with pancreatic duct cannulation,
      pyloric ligation, and bile diversion into duodenum, and 2.5, 5, and 10 nmol/kg
      PACAP-27 was administered intravenously while pancreatic juice was collected for
      30 minutes. In other groups of rats, the effect of 10 nmol/kg PACAP-27 was
      studied under the influence of either atropine; loxiglumide, an antisecretin
      serum; a combination of both loxiglumide and the antiserum; or a PACAP antagonist
      (PACAP 6-38). Plasma secretin and cholecystokinin concentrations were measured by
      radioimmunoassay. RESULTS: (1) PACAP dose-dependently increased pancreatic
      secretion of fluid, bicarbonate, and protein; (2) the increase in pancreatic
      secretion paralleled that of plasma secretin and cholecystokinin; (3) a
      combination of loxiglumide and antisecretin serum eliminated the PACAP-stimulated
      pancreatic secretion, whereas loxiglumide or antisecretin serum alone partially
      but significantly blocked pancreatic secretion; (4) atropine failed to influence
      PACAP-induced pancreatic secretion; and (5) PACAP antagonist profoundly
      suppressed the PACAP action. CONCLUSIONS: PACAP-27 dose-dependently stimulates
      pancreatic secretion of fluid, bicarbonate, and protein in rats. This effect is
      mediated by release of both secretin and cholecystokinin and is independent of
      cholinergic tone.

PMID- 9558298
TI  - Leukocyte-endothelial cell interactions: molecular mechanisms and implications in
      gastrointestinal disease.
AB  - Leukocyte-endothelial cell adhesion is now recognized to represent an early and
      rate-limiting step in the leukocyte infiltration and accompanying tissue injury
      that is associated with acute and chronic inflammatory diseases of the
      gastrointestinal tract. Adhesive interactions such as leukocyte rolling,
      adherence, and transendothelial migration are influenced by a variety of
      physical, chemical, and molecular factors that ultimately result in a net up
      regulation or down-regulation of the inflammatory response. Coordination of this
      process is made possible by the mediator-specific, time-sensitive expression of
      adhesion glycoproteins on the surface of leukocytes and/or vascular endothelial
      cells. In this review, the different families of relevant adhesion molecules that
      participate in the coordinated recruitment of leukocytes into inflamed tissue are
      described and then discussed in terms of the pathophysiological alterations
      observed in selected experimental models of gastrointestinal disease. These
      include ischemia/reperfusion injury, radiation enteritis, inflammatory bowel
      disease, and the inflammatory responses to substances liberated by Helicobacter
      pylori and Clostridium difficile.

PMID- 9558297
TI  - Hypercalcemia due to endogenous overproduction of 1,25-dihydroxyvitamin D in
      Crohn's disease.
AB  - Hypercalcemia may occur in various granulomatous diseases. Two patients with
      Crohn's disease who had hypercalcemia, hypercalciuria, and excessively high serum
      levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] are described. Both had numerous
      noncaseating, epithelioid granulomas in bowel biopsy samples. A direct
      correlation was observed between serum 1,25(OH)2D levels and both serum and
      urinary calcium concentrations. Also, calcium and 1,25(OH)2D levels strongly
      paralleled the clinical activity of disease. Prompt therapy with prednisone in
      the patient who had symptomatic hypercalcemia and with prednisone and mesalamine
      in the other patient without hypercalcemic symptoms led to normalization of
      calcium and serum 1,25(OH)2D levels, but 25-hydroxyvitamin D [25(OH)D] levels
      remained unchanged. Four months after discharge, recurrence of Crohn's disease
      symptomatology together with an increase in calcium and serum 1,25(OH)2D levels
      was observed in 1 patient; after increasing the prednisone dose, levels decreased
      and rapid clinical resolution was noted. These cases appear to be the first
      reported instances of hypercalcemia in patients with Crohn's disease. Excessive
      synthesis of 1,25(OH)2D may have been inhibited by an action of corticosteroids
      on the 1alpha-hydroxylation of 25(OH)D in the activated macrophage of Crohn's
      granulomas. Crohn's disease should be added to the list of granulomatous diseases
      responsible for 1,25(OH)2D-mediated hypercalcemia.

PMID- 9558299
TI  - Our new president--Donald O. Castell, M.D.

PMID- 9558300
TI  - Editorial 
AB  - As clinical dermatologists, we are all striving to achieve the highest possible
      accuracy in our clinical acumen and diagnostic skills. Over the past decade, one
      relatively simple advance, epiluminescence microscopy with the use of the
      dermatoscope, has significantly contributed to our diagnostic skills in the
      detection of benign versus pigmented lesions. In the paper by Kawabata and
      Tamaki, these authors delineate distinctive dermatoscopic features of acral
      lentiginous melanoma in situ, and contrast this with melanocytic nevi. The
      restructuring of healthcare delivery systems by third party payers and
      governmental programs is impacting on the pattern of our medical practices. In
      Canada, this has limited access to widespread use of techniques such as Mohs'
      micrographic surgery. The article by Arlette and colleagues has further supported
      the well-established studies indicating that Mohs' micrographic surgery for high
      risk skin cancers has a dramatic benefit. Healthcare restructuring has also led
      to a decreased number of trainees in a number of subspecialties, including
      dermatology. This decrease in manpower has been an impetus to look at alternative
      forms of care for underserviced areas. Telemedicine, the use of
      telecommunications technology to provide healthcare services over a distance, has
      been examined as one attempt at solving this problem. In the Point-Counterpoint
      articles, we have two distinct views on the future of telemedicine as it applies
      to dermatology. Over the past decade, there have been dramatic advances in our
      understanding at a molecular nature of various disease processes. This rapid
      development has translated into a large number of therapies. Regulatory agencies
      such as the Food and Drug Administration in the United States, or the Health
      Protection Branch in Canada, are caught between demands to bring effective
      therapies to the market in an expedited fashion, and yet establish efficacy and
      maintain safety of new therapeutic entities. This occurs by a multistaged
      approval process. During the early phases, exposure is limited in order to
      accumulate preliminary data on pharmacology and toxicity. In the Critical
      Appraisal CME series, Muglia and DiGiovanna describe early testing processes in
      Phase 1 clinical trials. Calciphylaxis is a severe disease associated with
      calcification of the skin, subcutaneous tissue and potentially, internal organs.
      While the disease itself is relatively uncommon, the manifestations are quite
      distinctive. In this issue of the Journal, we have a review of calciphylaxis from
      Richard Worth, as well as a preamble by Dr. Goodall and a case report by Kalaaji
      et al. illustrating the consequences of this rare but distinctive entity.

PMID- 9558301
TI  - Effect of occlusion on cell proliferation during epidermal healing.
AB  - BACKGROUND: Occlusive dressings influence epithelization of superficial wounds by
      some unknown mechanism(s). OBJECTIVE: The effects of occlusion on epidermal cell
      proliferation in two types of wounds were examined. METHODS: Partial-thickness
      wounds and tape-stripped skin wounds were compared. An immunohistochemical
      technique, employing PC10 - a monoclonal antibody against proliferating cell
      nuclear antigen (PCNA) - was applied to formalin-fixed, paraffin-embedded porcine
      tissue sections. RESULTS: The number of PC10-positive cells was low during the
      migratory phase, then increased to a peak of proliferation 2 to 3 days after
      resurfacing. An overall increased proliferative response (mean = 21%) was seen in
      occluded compared to control partial-thickness wounds (day 10 postoperatively);
      an opposite effect of occlusion on epidermal proliferation was seen in tape
      stripped skin. Occlusion decreased the proliferative response (mean = 42%)
      compared to air-exposure. CONCLUSION: Occlusion increased epidermal cell
      proliferation in wounds (where the entire surface epithelium and papillary dermis
      was removed), whereas an opposite effect was seen in tape-stripped skin from
      which only the stratum corneum had been removed.

PMID- 9558302
TI  - Distinctive dermatoscopic features of acral lentiginous melanoma in situ from
      plantar melanocytic nevi and their histopathologic correlation.
AB  - BACKGROUND: An acral lentiginous melanoma in situ on the sole is often difficult
      to differentiate with the naked eye from an acquired plantar melanocytic nevus.
      Recent technical advances in epiluminescence microscopy have contributed to the
      differentiation of these two pigmented skin lesions. OBJECTIVE: In this study,
      the correlation between dermatoscopic and histopathologic findings of acral
      lentiginous melanoma in situ on the sole are compared to those of acquired
      plantar melanocytic nevi. METHODS: Three acral lentiginous melanomas in situ on
      the sole, and two cases of acral lentiginous melanoma were compared with 50
      acquired plantar melanocytic nevi by means of dermatoscopy and histopathology.
      RESULTS: The dermatoscopic surface profiles of acquired melanocytic nevi were
      composed of linear pigmentation accentuated mainly on the sulcus superficialis.
      Histologically, some areas of the sulcus superficialis corresponded to rete
      ridges of the epidermis, and nests of nevus cells were also often located there.
      In contrast, the acral lentiginous melanomas in situ showed diffuse, irregularly
      shaped pigmentation distributed in a disorderly fashion over the entire surface.
      Histologically, isolated areas of proliferation and small nest formations of
      atypical melanocytes were irregularly distributed in the epidermis. CONCLUSION: A
      distinctive dermatoscopic feature of acral lentiginous melanoma in situ is
      diffuse and irregular pigmentation over the entire surface of the lesion. This
      feature is helpful for differentiating acral lentiginous melanoma in situ from
      acquired plantar melanocytic nevi.

PMID- 9558303
TI  - Basal cell carcinoma of the periocular region.
AB  - BACKGROUND: Basal cell carcinomas of the periocular area present a particular
      challenge because of the likelihood of damage to vital structures. OBJECTIVE:
      More than 10-years experience of treating basal cell carcinomas by Mohs
      micrographic surgery was reviewed. METHODS: Chart analysis of 233 periocular
      basal cell carcinomas was performed. All patients were contacted either in
      clinical follow-up or by telephone review. RESULTS: Two hundred and thirty-three
      periocular basal cell carcinomas were analyzed out of a total of 3, 192 basal
      cell carcinomas treated during this period (7.3%). Patients ranged in age from 17
      to 102 years with a mean age of 58.8 years and a median of 59.0 years. Of the
      patients, 54.5% were female. Mohs micrographic surgery was the prime therapy in
      177 patients (75. 9%). Of the lesions, 48.5% occurred in the medial canthal area,
      35. 2% on the lower eyelid, 10.7% on the upper eyelid, and 5.6% on the lateral
      canthus. There was no significant difference between the left/right distribution
      in males and females. The average follow-up time was 34 months (standard
      deviation 26.38 months). A cumulative rate of no recurrence tabulated by modified
      life table analysis was 0.9864. CONCLUSION: This study further documents the
      problems associated with basal cell carcinoma of the periocular area as well as
      the value of Mohs micrographic surgery as treatment.

PMID- 9558304
TI  - Direct immunofluorescence diagnosis of pemphigus without biopsy.
AB  - BACKGROUND: Direct immunofluorescence (DIF) is a necessary examination tool for
      the diagnosis of pemphigus. The suction-blister-method splits the skin at the
      lamina lucida and it is possible with a scalpel to separate the entire epidermis
      from the dermis. OBJECTIVE: The study was to determine whether DIF is reliable on
      epidermal sheets separated using a suction apparatus. METHODS: Thirteen patients
      were selected for this study: (nine with pemphigus vulgaris (PV), one with
      paraneoplastic pemphigus (PP), and three with pemphigus erythematosus (PE).
      Frozen epidermal sheets, separated from the dermis with a scalpel, were used as a
      substrate. Diagnosis with routine fluorescein isothiocyanate (FITC) antibodies
      was made. RESULTS: In all patients a pericellular deposition of IgG was evident
      and in eight of these patients a pericellular deposition of C3 was present. In
      two cases of PE and one of PP, the C3 deposits were also present in the lower
      part of basal keratinocytes. CONCLUSION: This diagnostic method without skin
      biopsy is easy to perform and, together with the histology and clinical aspects,
      could be a useful tool in the diagnosis of pemphigus. We recommend this method
      when the patient is allergic to local anaesthetics, the patient easily produces
      hypertrophic scars, or in follow-up of already biopsied patients.

PMID- 9558305
TI  - Lymphoid markers, activation markers, and adhesion molecules in cutaneous biopsy
      specimens from HIV+ patients with disease progression. The Military Medical
      Consortium for the Advancement of Retroviral Research.
AB  - BACKGROUND: One important factor in understanding the pathogenesis of human
      immune deficiency virus (HIV) disease is documenting the patterns of immune
      dysregulation present in HIV-positive patients. The cells which home to skin are
      mainly certain subsets of T cells and, as opposed to the peripheral blood, where
      circulating factors may inhibit terminal phenotypic differentiation, the
      cutaneous environment potentiates differentiation during cutaneous eruptions.
      OBJECTIVE: The authors' aim was to characterize the inflammatory dermatoses in
      biopsy specimens from HIV-positive patients with immunohistochemical stains for
      lymphoid markers, activation markers, and adhesion molecules and to determine if
      there was any correlation with the type of dermatosis and the HIV-disease stage.
      METHODS: Lymphoid and activation markers as well as adhesion molecules were
      studied on cutaneous biopsy specimens from 96 inflammatory dermatoses in HIV
      positive patients. The dermatoses included psoriasiform dermatoses with and
      without a lichenoid component, perivascular lymphoid dermatoses, perivascular and
      periadnexal inflammatory dermatoses, spongiotic dermatoses, granulomatous
      dermatoses, and neutrophilic dermatoses with and without vasculitis. RESULTS:
      Although there was a decrease in CD4/CD8 ratios in the cutaneous inflammatory
      dermatoses with progression of the disease, the ratios of CD4/CD8 cells were far
      higher than those in the peripheral blood. There were also increasing numbers of
      CD23+ cells and increased E-Selectin expression on endothelial cells from the
      early stages of disease, with no consistent pattern of ICAM-1 expression on
      epithelial cells with disease progression. CONCLUSIONS: The expression of
      lymphoid markers, activation markers, and adhesion molecules in the skin with
      progression of HIV disease, is consistent with a T helper (Th)1 to Th0/Th2
      cytokine pattern of immune dysregulation. This cytokine pattern may be modified
      by the cytopathic effects of HIV on lymphoid and dendritic populations and by
      effects of other concurrent infections. Significant numbers of CD4+ T cells in
      skin infiltrates, with low peripheral CD4 T-cell counts, suggest that the
      cutaneous T-cell populations may be distinctive.

PMID- 9558306
TI  - Undergraduate dermatology education in Canada: a survey.
AB  - BACKGROUND: Two reviews done in the 1980's showed that many Canadian medical
      schools scheduled relatively little time for dermatological teaching. Many
      students did not have a real clinical exposure to dermatology. OBJECTIVE: The
      purpose of this study was to obtain new data to reevaluate the undergraduate
      training in dermatology in Canada. METHODS: A survey was sent to the coordinators
      of undergraduate dermatology of all 16 Canadian medical schools. RESULTS: The
      survey of medical schools demonstrates the current status of dermatology
      undergraduate teaching across Canada. Although many improvements have been made
      in the way dermatology is taught to medical students, many of the problems
      noticed in the 1980s remain unresolved. CONCLUSION: Because dermatological care
      in Canada is often rendered by nondermatologists, the dermatologists should
      emphasize the importance of undergraduate training in their specialty.

PMID- 9558307
TI  - Phase 1 clinical trials.
AB  - BACKGROUND: In the United States, drug development and approval is a complex
      process regulated by the Food and Drug Administration under the authority
      outlined in the Code of Federal Regulation. The goal of this multi-step process
      is to determine safety and efficacy of new therapeutic entities. Initially,
      exposure of humans to new therapeutic agents is accomplished in a graded and
      limited fashion. This approach seeks to minimize risks to study participants from
      exposure to damaging agents. During early phases, limiting exposure to a few
      individuals results in the accumulation of preliminary data on pharmacology,
      short-term toxicity, and efficacy. The inherent limitations of this process
      necessitate careful critique and caution in extrapolation of phase 1 data.
      OBJECTIVES: The purpose of this article is to provide a review of the drug
      approval process focusing on phase 1 trials, which are the earliest human
      exposure to a new drug. The purpose, variations, and significance of phase 1
      trials are described, and a framework is provided to critically evaluate data
      published from these trials. CONCLUSIONS: Phase 1 trials are primarily designed
      to accumulate short-term safety (toxicity) and pharmacological data. Although
      preliminary efficacy may be addressed ("proof of concept" efficacy), it is a
      secondary endpoint. The numbers of patients are small, the numbers of patients
      receiving efficacious doses are very small, and controls are absent. Evaluation
      of efficacy and of long-term toxicity requires longer, larger, and controlled
      studies.

PMID- 9558308
TI  - Calciphylaxis: a cause of necrotic ulcers in renal failure.
AB  - BACKGROUND: Calciphylaxis is a rare and life-threatening condition occurring in
      patients with end-stage renal disease on dialysis. The diagnosis is frequently
      delayed or missed and therapy is often unsuccessful. OBJECTIVE: The clinical and
      pathological components of calciphylaxis are emphasized in a patient that may
      facilitate early diagnosis and initiation of therapy. RESULTS: Early recognition
      of the clinical signs and symptoms of calciphylaxis is crucial. The tissue
      diagnosis requires large elliptical biopsies because histological findings are
      segmental and often missed. CONCLUSION: Early diagnosis and intervention in
      calciphylaxis is critical. Parathyroidectomy should be considered in all cases.

PMID- 9558309
TI  - Calciphylaxis: pathogenesis and therapy.
AB  - BACKGROUND: Calciphylaxis is a rare, painful and debilitating disease in which
      calcification of the skin and subcutaneous tissues or of internal organs can lead
      to skin necrosis, discolouration, and other skin lesions. The typical patient has
      end-stage renal disease (ESRD) and hyperparathyroidism. Selye originally
      characterized this syndrome in rats and distinguished it from other syndromes of
      abnormal calcification by the following sequence: sensitizers, latent period, and
      challengers. There has been recent debate regarding misdiagnosis and failure to
      differentiate this category of patients even in clinical studies. OBJECTIVE: In
      this article the clinical manifestations of calciphylaxis are described; the
      importance of distinguishing this condition from other calcification syndromes is
      explained; risk factors, sensitizers, and challenges are reviewed; treatments of
      choice are discussed; and the merits of parathyroidectomy are evaluated.
      CONCLUSION: It is important to consider calciphylaxis in a differential diagnosis
      of calcification syndromes and in treating patients with ESRD and
      hyperparathyroidism, because early diagnosis and treatment can interrupt the
      progression of the disease process; the disease is painful and debilitating; and
      inappropriate treatment such as corticosteroid administration may aggravate the
      condition. Skin biopsy is an important diagnostic tool when the condition is
      suspected. Parathyroidectomy may be justified because the untreated disease
      itself has significant rates of morbidity and mortality and because this
      treatment occasionally leads to dramatic clinical improvement.

PMID- 9558310
TI  - Photoaffinity labeling of oxidosqualene cyclase and squalene cyclase by a
      benzophenone-containing inhibitor.
AB  - A new orally active oxidosqualene:lanosterol cyclase (OSLC) inhibitor (Ro48-8071;
      Morand, O. H. et al. (1997) J. Lipid Res. 38, 373-390) showed potent
      noncompetitive inhibition of bacterial squalene:hopene cyclase (SHC) from
      Alicyclobacillus acidocaldarius (IC50 = 9.0 nM, KI = 6.6 nM) and OSLC (IC50 = 40
      nM, KI = 22 nM for homogeneous rat liver OSLC). A tritium-labeled isotopomer
      (18.8 Ci/mmol) of this nonterpenoid inhibitor, which possesses a benzophenone
      (BP) photophore, was chemically synthesized as a photoaffinity label. Specific,
      efficient covalent modification of both OSLC and SHC enzymes was observed after
      UV irradiation at 360 nm. Labeling of both OSLC and SHC by [3H]Ro48-8071 was
      competitively displaced by coincubation with a 1000-fold molar excess of 18-thia
      2, 3-oxidosqualene or the nonterpenoid inhibitor BIBX79. Displacement of labeling
      of OSLC was also achieved with the suicide substrate (3S)-29-methylidene-2,3
      oxidosqualene. Thus, the nonsubstrate Ro48-8071 and both terpenoid and
      nonterpenoid inhibitors of these enzymes appear to share a common binding site.

PMID- 9558311
TI  - Pressure denaturation of proteins: evaluation of compressibility effects.
AB  - One of the key pieces of information from pressure denaturation experiments is
      the standard volume change for unfolding (Delta V(o)). The pressure dependence of
      the volume change, the standard compressibility change (Delta K(o)T), is
      typically assumed to be zero in the analysis of these experiments. We show here
      that this assumption can be incorrect and that the neglect of compressibility
      differences can skew the interpretation of experimental results. Analysis of
      experimental, variable-pressure NMR data for bovine pancreatic ribonuclease A in
      2H2O at pH 2.0 and 295 K yielded the following statistically significant, non
      zero values: Delta K(o) T = 0.015 +/- 0.002 mL mol-1 bar-1, Delta V(o) = -21 +/-
      2 mL mol-1, and Delta G(o) = 2.8 +/- 0.3 kcal mol-1. The experimental protein
      stability is in good agreement with one (Delta G(o) = 2.5 kcal mol-1) determined
      independently for the same protein by calorimetry at atmospheric pressure under
      equivalent conditions [Makhatadze, G. I., Clore, G. M., and Gronenborn, A. M.
      (1995) Nat. Struct. Biol. 2, 852-855]. The positive value for Delta K(o)T
      indicates that the denatured form of ribonuclease A is more compressible than the
      native form; this is explained in terms of an interplay between the intrinsic
      compressibility of the protein and solvation effects. When the same data were
      fitted to a model that assumes a zero compressibility change, the Delta G(o)
      value of 4. 0 +/- 0.1 kcal mol-1 returned by the model no longer agreed with the
      independent measurement, and the Delta V(o) returned by the model was a very
      different -59 +/- 1 mL mol-1. By contrast, it was not possible to carry out a
      similar thermodynamic analysis of fluorescence spectroscopic data for the
      denaturation of staphylococcal nuclease to yield well-defined values of Delta
      G(o), Delta V(o), and Delta K(o)T. This limitation was shown by evaluation of
      synthetic data to be intrinsic to spectroscopic data whose analysis requires
      fitting of the plateaus at either side of the transition. Because NMR data do not
      have this requirement, they can be analyzed more rigorously.

PMID- 9558312
TI  - Molecular basis of resistance to HIV-1 protease inhibition: a plausible
      hypothesis.
AB  - The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and
      the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the
      cleavage sites in the gag, gag-pol polyproteins, have been measured by direct
      microcalorimetric analysis. The results indicate that the binding of the peptide
      substrate or peptide inhibitor is entropically driven; i.e., it is characterized
      by an unfavorable enthalpy and a favorable entropy change, in agreement with a
      structure-based thermodynamic analysis based upon an empirical parameterization
      of the energetics. Dissection of the binding enthalpy indicates that the
      intrinsic interactions are favorable and that the unfavorable enthalpy originates
      from the energy cost of rearranging the flap region in the protease molecule. In
      addition, the binding is coupled to a negative heat capacity change. The dominant
      binding force is the increase in solvent entropy that accompanies the burial of a
      significant hydrophobic surface. Comparison of the binding energetics obtained
      for the substrate with that obtained for synthetic nonpeptide inhibitors
      indicates that the major difference is in the magnitude of the conformational
      entropy change. In solution, the peptide substrate has a higher flexibility than
      the synthetic inhibitors and therefore suffers a higher conformational entropy
      loss upon binding. This higher entropy loss accounts for the lower binding
      affinity of the substrate. On the other hand, due to its higher flexibility, the
      peptide substrate is more amenable to adapt to backbone rearrangements or subtle
      conformational changes induced by mutations in the protease. The synthetic
      inhibitors are less flexible, and their capacity to adapt is more restricted. The
      expected result is a more pronounced effect of mutations on the binding affinity
      of the synthetic inhibitors. On the basis of the thermodynamic differences in the
      mode of binding of substrate and synthetic inhibitors, it appears that a key
      factor to understanding resistance is given by the relative balance of the
      different forces that contribute to the binding free energy and, in particular,
      the balance between conformational and solvation entropy.

PMID- 9558313
TI  - Penetration and intracellular routing of nucleus-directed peptide-based shuttles
      (loligomers) in eukaryotic cells.
AB  - Loligomers are multitasking, peptide-based shuttles that are able to penetrate
      cells and self-localize into distinct cellular compartments. In particular,
      loligomer 4 incorporates internalization and nuclear import sequences as well as
      reporter groups. The intracellular routing of loligomer 4 was analyzed by
      microscopy and flow cytometry, to define and demonstrate localization events.
      Electron micrographs of CHO cells exposed to a biotinylated derivative of
      loligomer 4 as well as confocal images of CHO cells treated with rhodamine
      labeled loligomer 4 indicate their presence in the cytosol, endocytic vesicles,
      and the nucleus of CHO cells. Loligomer 4 accumulates irreversibly inside cells.
      Uptake of loligomer 4 by six mammalian cell lines (Daudi, EL4, CHO, COS-7, VERO,
      and HeLa) was proven by flow cytometry, establishing the generality of the
      principle. Cells presented as monolayers typically were less able to endocytose
      the construct than cells grown in suspension. Cellular accumulation of loligomer
      4 varied between cell lines with COS-7 and VERO cells showing the highest level
      of uptake. Plasmids harboring reporter genes could be transported efficiently
      inside CHO cells, suggesting that loligomer 4 either alone or noncovalently
      associated with large macromolecules can effectively reach the nucleus of cells.
      In summary, loligomer 4 constructs provide a simple synthetic platform for the
      design of guided intracellular agents.

PMID- 9558314
TI  - Solution structure of an intramolecular DNA triplex linked by hexakis(ethylene
      glycol) units: d(AGAGAGAA-(EG)6-TTCTCTCT-(EG)6-TCTCTCTT).
AB  - A DNA molecule was designed and synthesized with three octanucleotide stretches
      linked by two hexakis(ethylene glycol) chains to form an intramolecular triplex
      in solution. The structural data obtained from a series of NMR NOESY spectra
      yielded interproton distances, and COSY experiments provided dihedral angle
      information for analysis of deoxyribose ring pucker. Using distance geometry
      followed by simulated annealing with restrained molecular dynamics and relaxation
      matrix refinement, a well-refined ensemble of conformations was calculated.
      Although some NOE cross-peaks involving protons of the hexakis(ethylene glycol)
      linker could be identified, most could not be assigned and the conformations of
      the linkers were not determined. The deoxyribose conformations are predominantly
      of the S type, except for the protonated cytosine residues in the third strand
      which show hybrid N and S character. Overall, the duplex part of the molecule
      resembles a B-DNA double helix with the third strand bound in its major groove by
      Hoogsteen hydrogen bonds. This structure provides a basis for comparison with
      triplexes containing noncanonical or nonnatural nucleotides.

PMID- 9558315
TI  - Solution structure of an intramolecular DNA triplex containing 5-(1-propynyl)-2'
      deoxyuridine residues in the third strand.
AB  - Incorporation of the modified base 5-(1-propynl)-2'-deoxyuridine (propynylU) in
      the third strand of a triplex leads to enhanced triplex stabilization. To
      investigate effects of the propyne nucleotide on triplex structure and the
      factors underlying the increased stability, we have determined the solution
      structure of the intramolecular DNA pyrmidine-purine-pyrimdine d(AGAGAGAA-(EG)6
      TTCTCTCT-(EG)6-PCPCPCPP) (PDD-EG), which contains 5-(1-propynl)-2'-deoxyuridine
      (P) in the third strand and hexakis(ethylene glycol) linkers [(EG)6]. The
      structure was calculated using X-PLOR with distance and dihedral angle restraints
      obtained from two-dimensional NMR experiments and refined with the direct
      relaxation matrix method. The structures show that the extended aromatic electron
      cloud of the propynylU nucleotide stacks well over the 5'-neighboring
      nucleotides, resulting in increased stabilization. The propynylU nucleotides also
      affect the overall structure of the triple helix. A comparison of the structure
      to that of the nonmodified intramolecular DNA triplex of the same sequence,
      d(AGAGAGAA-(EG)6-TTCTCTCT-(EG)6-TCTCTCTT) (DDD-EG), shows that PDD-EG has a more
      A-DNA like X displacement and inclination than DDD-EG yet still maintains
      predominantly S-type sugar puckers as found in DDD-EG and other DNA triplexes.

PMID- 9558316
TI  - Fidelity of mutant HIV-1 reverse transcriptases: interaction with the single
      stranded template influences the accuracy of DNA synthesis.
AB  - We have used random sequence mutagenesis and complementation in a bacterial
      selection system to establish a large library of immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT) mutants with amino acid substitutions in the
      beta3-beta4 region of the fingers subdomain [Kim, B., Hathaway, T. R., and Loeb,
      L. A. (1996) J. Biol. Chem. 271, 4872-4878]. We show here that one of these
      mutants, D76V, exhibits increased accuracy of copying both DNA and RNA templates
      in a primer extension assay with biased dNTP pools. More detailed analysis of DNA
      dependent polymerization showed that the D76V mutation conferred an up to 14-fold
      increase in fidelity of nucleotide insertion and a 9-fold reduced mutation rate
      in an M13mp2 lacZalpha forward mutation assay. Substitution at D76 with
      positively charged (D76R) and nonpolar (D76V and D76I) residues increased
      replicational accuracy, while substitutions with negatively charged (D76E) and
      polar residues (D76S and D76C) had little effect on fidelity. We propose that D76
      affects replicational accuracy by mediating interaction between the fingers
      subdomain and the single-stranded template. Our work shows that the Escherichia
      coli complementation system can yield HIV RT mutants with increased fidelity that
      have not been isolated from the natural host and that are valuable in
      understanding the molecular bases of replicational accuracy.

PMID- 9558317
TI  - Characterization of Y122F R2 of Escherichia coli ribonucleotide reductase by time
      resolved physical biochemical methods and X-ray crystallography.
AB  - Ribonucleotide reductase (RNR) from Escherichia coli catalyzes the conversion of
      ribonucleotides to deoxyribonucleotides. It is composed of two homodimeric
      subunits, R1 and R2. R2 contains the diferric-tyrosyl radical cofactor essential
      for the nucleotide reduction process. The in vitro mechanism of assembly of this
      cluster starting with apo R2 or with a diferrous form of R2 has been examined by
      time-resolved physical biochemical methods. An intermediate, Fe3+/Fe4+ cluster
      (intermediate X), has been identified that is thought to be directly involved in
      the oxidation of Y122 to the tyrosyl radical (*Y122). An R2 mutant in which
      phenylalanine has replaced Y122 has been used to accumulate intermediate X at
      sufficient levels that it can be studied using a variety of spectroscopic
      methods. The details of the reconstitution of the apo and diferrous forms of
      Y122F R2 have been examined by stopped-flow UV/vis spectroscopy and by rapid
      freeze quench electron paramagnetic resonance, and Mossbauer spectroscopies. In
      addition the structure of this mutant, crystallized at pH 7.6 in the absence of
      mercury, at 2.46 A resolution has been determined. These studies suggest that
      Y122F R2 is an appropriate model for the examination of intermediate X in the
      assembly process. Studies with two mutants, Y356F and double mutant Y356F and
      Y122F R2, are interpreted in terms of the possible role of Y356 in the putative
      electron transfer reaction between the R1 and R2 subunits of this RNR.

PMID- 9558318
TI  - Preparation, characterization, and complete heteronuclear NMR resonance
      assignments of the glutaredoxin (C14S)-ribonucleotide reductase B1 737-761
      (C754S) mixed disulfide.
AB  - The first committed step in de novo DNA biosynthesis involves the conversion of
      ribonucleotides to the corresponding deoxyribonucleotides catalyzed by the enzyme
      ribonucleotide reductase. Reduction of disulfides in ribonucleotide reductase is
      essential and is catalyzed by the protein disulfide reductants glutaredoxin or
      thioredoxin. The interaction region between Escherichia coli glutaredoxin-1 and
      E. coli ribonucleotide reductase has been localized to the C-terminal end of the
      B1 subunit of ribonucleotide reductase. We have demonstrated that a 25-residue
      peptide corresponding to this C-terminal sequence is a very good substrate for
      glutaredoxin via a fluorescence assay and that this peptide binds in a specific
      manner via isothermal titration calorimetric measurements. By selectively
      mutating the two cysteines in the peptide, we have identified the electrophilic
      cysteine as C759 (B1 numbering) and prepared a mixed disulfide between E. coli
      glutaredoxin-1 (C14 --> S) and the C759 monothiol form of the peptide. The
      peptide and the protein have been labeled with 13C and 15N, and complete
      heteronuclear NMR resonance assignments have been completed for both the peptide
      and the protein in the complex. By using half-filtered NOESY spectra,
      intermolecular NOEs between the protein and the peptide have been identified and
      the binding site on glutaredoxin has been mapped. The electrostatic charge
      distribution of the protein in this region is very positive, thus providing an
      excellent match for the highly negatively charged peptide. In addition, the
      electrostatic potential of the peptide provides a rationale for the observed
      cysteine selectivity in the reaction between glutaredoxin and the B1 peptide.

PMID- 9558319
TI  - Transcriptional activator-coactivator recognition: nascent folding of a kinase
      inducible transactivation domain predicts its structure on coactivator binding.
AB  - A model of transcriptional activator-coactivator recognition is provided by the
      mammalian CREB activation domain and the KIX domain of coactivator CBP. The CREB
      kinase-inducible activation domain (pKID, 60 residues) is disordered in solution
      and undergoes an alpha-helical folding transition on binding to CBP
      [Radhakrishan, I., Perez-Alvarado, G. C., Parker, D., Dyson, H. J., Montminy, M.
      R., and Wright, P. E. (1997) Cell 91, 741-752]. Binding requires phosphorylation
      of a conserved serine (RPpSYR) in pKID associated in vivo with the biological
      activation of CREB signaling pathways. The CBP-bound structure of CREB contains
      two alpha-helices (designated alphaA and alphaB) flanking the phosphoserine; the
      bound structure is stabilized by specific interactions with CBP. Here, the
      nascent structure of an unbound pKID domain is characterized by multidimensional
      NMR spectroscopy. The solubility of the phosphopeptide (46 residues) was enhanced
      by truncation of N- and C-terminal residues not involved in pKID-CBP
      interactions. Although disordered under physiologic conditions, the pKID fragment
      and its unphosphorylated parent peptide exhibit partial folding at low
      temperatures. One recognition helix (alphaA) is well-defined at 4 degreesC,
      whereas the other (alphaB) is disordered but inducible in 40% trifluoroethanol
      (TFE). Such nascent structure is independent of serine phosphorylation and
      correlates with the relative extent of engagement of the two alpha-helices in the
      pKID-KIX complex; whereas alphaA occupies a peripheral binding site with few
      intermolecular contacts, the TFE-inducible alphaB motif is deeply engaged in a
      hydrophobic groove. Our results support the use of TFE as an empirical probe of
      hidden structural propensities and define a correspondence between induced fit
      and the nascent structure of peptide fragments.

PMID- 9558320
TI  - Thermodynamics of bovine spleen galectin-1 binding to disaccharides: correlation
      with structure and its effect on oligomerization at the denaturation temperature.
AB  - Isothermal titration calorimetry (ITC) measurements of the binding 1-beta
      carbohydrate-substituted galactopyranoside derivatives to galectin-1 from bovine
      spleen, a dimer with one binding site per subunit, were performed at 283-285 and
      298 K. The disaccharides were lactose, methyl beta-lactoside, lactulose, 4-O-beta
      D-galactopyranosyl-D-mannopyranoside, 3-O-beta-D-galactopyranosyl-D-arabinose, 2'
      O-methyllactose, lacto-N-biose, N-acetyllactosamine, and thiodigalactopyranoside.
      The site binding enthalpies, DeltaHb, are the same at both temperatures and range
      from -42.2 +/- 3.3 kJ mol-1 for thiodigalactopyranoside to -24.5 +/- 0.5 kJ mol-1
      for lacto-N-biose, and the site binding constants range from 4.86 +/- 0.78 x
      10(3) M-1 for methyl beta-lactoside at 297.8 K to 6.54 +/- 0.97 x 10(4) M-1 for N
      acetyllactosamine at 281.3 K. The binding reactions are enthalpically driven,
      exhibit enthalpy-entropy compensation, and, with the exception of N
      acetyllactosamine, follow a van't Hoff dependence of the binding constant on
      temperature. The number of contacts at distances <4.0 A between the disaccharide
      and galectin was determined from the energy-minimized conformation of the complex
      derived from the X-ray crystallographic structure of the galectin-N
      acetyllactosamine complex determined by Liao et al. [Liao, D. I., Kapadia, G.,
      Ahmed, H., Vasta, G. R., and Herzberg, O. (1994) Proc. Natl. Acad. Sci. U.S.A.
      91, 1428-1432]. The binding enthalpies calculated from changes in the solvent
      accessible surface areas of the galectin binding site upon binding of the
      disaccharide were in close agreement with the experimental values for lactose,
      lactulose, lacto-N-biose, and N-acetyllactosamine, all of which exhibit binding
      enthalpies >-36 kJ mol-1. Differential scanning calorimetry measurements on
      solutions of galectin and its disaccharide complexes show that the galectin dimer
      does not dissociate upon denaturation in contrast to the legume lectins. At the
      denaturation temperature, the galectin in the absence of sugar exists as a
      tetramer, and the extent of this association is substantially reduced in the
      presence of a disaccharide.

PMID- 9558321
TI  - Pressure dependence of amide hydrogen-deuterium exchange rates for individual
      sites in T4 lysozyme.
AB  - We report measurements of the pressure dependence of rate constants for the
      exchange of amide residue protons with solvent deuterium for T4 lysozyme. Data
      obtained at nine pressures from 0.1 to 200 MPa are analyzed using an elementary
      kinetic model and the formalism of transition state theory which yield activation
      volumes for the exchange process. Resolution of individual amide sites was
      accomplished using the HSQC two-dimensional (2D) NMR experiment on uniformly
      (15)N-labeled protein. The observed activation volumes span the range from 2.75
      to -25.1 mL/mol at 22 degreesC and pH* 7.5. When corrected for the pressure
      dependence of the ionic product for water and for the reported activation volume
      for the amide exchange reaction in model compounds, the portion of the activation
      volume associated with the accessibility of the solvent or catalyst to the amide
      sites ranges from -15.1 to 12.8 mL/mol. There is no simple correlation between
      the activation volumes and the protection factors for amide hydrogen exchange.
      The activation volumes for residues in close proximity in either the primary
      sequence or the folded structure may differ considerably. There is no trivial
      correlation between the activation volume and the secondary structural unit in
      which a residue is located, and activation volumes for residues that are
      apparently structurally coupled may be very different. The modest sizes of the
      activation volumes obtained under these conditions are in contrast to large
      values reported for bovine pancreatic trypsin inhibitor at more extreme
      conditions of 60 degreesC and pH* 8 where major unfolding events or structural
      rearrangements may dominate the mechanism [Wagner, G. (1983) Q. Rev. Biophys. 16,
      1-57].

PMID- 9558322
TI  - Structural examination of the influence of phosphorylation on the binding of
      fibrinopeptide A to bovine thrombin.
AB  - Upon addition of thrombin, fibrinopeptides A and B are cleaved off from the N
      termini of four chains of fibrinogen (Aalpha Bbeta gamma)2, and sites of
      polymerization are exposed, resulting in formation of a fibrin clot. For the
      fibrinogen Aalpha chain, cleavage occurs most prevalently at the Arg16-Gly17
      peptide bond. About 25-30% of the human fibrinogen Aalpha chains are
      phosphorylated in nature at the position of Ser3, but the function for this
      modification is not understood. Previous NMR studies indicated that the N
      terminal portion (1ADSGE5) of unphosphorylated fibrinopeptide A does not interact
      with the surface of bovine thrombin. Kinetic and NMR studies have now been
      carried out to assess whether phosphorylation at Ser3 allows the N-terminal
      segment (1ADSGEGDFLAEGGGVR16) to become anchored on the thrombin surface, leading
      to formation of a catalytically more efficient enzyme-substrate complex. Kinetic
      results indicate that phosphorylation leads to an approximately 65% increase in
      substrate specificity (kcat/Km) toward hydrolysis of fibrinogen Aalpha(1-20). 31P
      NMR studies reveal that the phosphorylated group does interact with thrombin, and
      1H line broadening studies suggest that phosphorylation does promote binding of
      amino acids 1-5. Two-dimensional transferred nuclear Overhauser effect
      spectroscopy studies of bound fibrinopeptide A(1-16 Ser3P) indicate that
      phosphorylation allows new through-space interactions involving amino acid
      residues 1ADSGE5 to be observed. Computational docking of the peptide onto the X
      ray structure of thrombin suggests that the phosphate may interact with basic
      residues at the rim of the heparin binding site of thrombin. As a result, the
      phosphate may serve as an anionic linker between the fibrinopeptide and the
      enzyme thrombin.

PMID- 9558323
TI  - The p51 subunit of human immunodeficiency virus type 1 reverse transcriptase is
      essential in loading the p66 subunit on the template primer.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a
      dimeric enzyme consisting of p66 and p51 subunits. The functional role of the p51
      subunit remains elusive since all the catalytic functions appear to be executed
      through the p66 subunit. We report here that the p51 subunit, in addition to
      providing structural support to the p66 subunit, may be involved in facilitating
      the loading of the p66 subunit on to the template-primer (TP). This possibility
      is supported by following observations: (i) Upon binding to the TP, the p51
      subunit can be dissociated by acetonitrile treatment and the template-primer
      bound p66 monomer alone is capable of catalyzing DNA synthesis. (ii) Photo-cross
      linking of template-primer to HIV-1 RT is abolished by dissociation of the p51
      subunit prior to the TP binding but remains unaffected after the TP binding step.
      (iii) The p66-TP covalent complex selectively generated by UV irradiation and
      separated by gel electrophoresis can incorporate a single nucleotide in situ upon
      its renaturation in the gel. (iv) Treatment of HIV-1 RT with (tert
      butyldimethylsilyl)spiroaminooxathioledioside (TSAO), an inhibitor that
      specifically binds to the beta7 beta8 loop of p51, destabilizes the heterodimeric
      enzyme, resulting in the subsequent loss of DNA binding.

PMID- 9558324
TI  - Structure of cyclodextrin glycosyltransferase complexed with a derivative of its
      main product beta-cyclodextrin.
AB  - Crystals of the inactive mutant Glu257-->Ala of cyclodextrin glycosyltransferase
      were soaked with the cyclodextrin (CD) derivative S-(alpha-D-glucopyranosyl)-6
      thio-beta-CD. The structural analysis showed its beta-CD moiety with no density
      indication for the exocyclic glucosyl unit. For steric reasons, however, the
      position of this unit is restricted to be at only two of the seven glucosyl
      groups of beta-CD. The analysis indicated that the enzyme can cyclize branched
      alpha-glucans. The ligated beta-CD moiety revealed how the enzyme binds its
      predominant cyclic product. The conformation of the ligated beta-CD was
      intermediate between the more symmetrical conformation in beta-CD dodecahydrate
      crystals and the conformation of a bound linear alpha-glucan chain. Its scissile
      bond was displaced by 2.8 A from the position in linear alpha-glucans.
      Accordingly, the complex represents the situation after the cyclization reaction
      but before diffusion into the solvent, where a more symmetrical conformation is
      assumed, or the equivalent state in the reverse reaction. Furthermore, a unifying
      nomenclature for oligosaccharide-binding subsites in proteins is proposed.

PMID- 9558325
TI  - Diradylglycerols alter fatty acid inhibition of monoacylglycerol acyltransferase
      activity in Triton X-100 mixed micelles.
AB  - The activity of hepatic monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22), a
      developmentally expressed microsomal enzyme, is inhibited by long-chain fatty
      acids, and stimulated by its product 1, 2-diacyl-sn-glycerol. Because the
      quantities of fatty acids and diacylglycerols are likely to vary in membranes
      during different physiological conditions and could thereby alter MGAT activity,
      we examined their combined effects on MGAT in Triton X-100/phospholipid mixed
      micelles. MGAT's product, 1,2-diC18:1-sn-glycerol, which is also normally a
      cooperative activator of the activity, reversed the 50% inhibition caused by 10
      mol % oleic acid. The presence of oleic acid also allowed low concentrations (<10
      mol %) of 1, 2-diC18:1-sn-glycerol to stimulate MGAT activity without the lag
      that is observed in the absence of fatty acid. At 12.6 mol %, 1, 2-monoC18:1-sn
      glycerol ether, which alone has no effect on MGAT activity, became an activator
      in the presence of 10 mol % oleic acid. Kinetic studies revealed that in the
      presence of 15 mol % oleic acid, 1,2-diC18:1-sn-glycerol ether increased the
      apparent Vmax by 3. 8-fold while minimally altering the apparent Km for palmitoyl
      CoA. Other neutral lipids including tri-C18:1-glycerol, ceramide, and cholesterol
      oleate did not stimulate MGAT in either the presence or the absence of fatty
      acid. Assay conditions altered MGAT's apparent relative preferences for potential
      monoradylglycerol substrates. The presence of phospholipids and of MGAT's 1,2
      diacyl-sn-glycerol product increased the enzyme's apparent preference for its 2
      monoacyl-sn-glycerol substrate by selectively increasing the apparent Vmax 2.7
      fold only when 2-monoC18:1-sn-glycerol was the substrate. Thus, in addition to
      previously reported regulation of MGAT by phospholipids and intracellular lipid
      second messengers, these studies lend additional support to the hypothesis that
      changes in other membrane-associated lipids, such as long-chain fatty acids and
      diradylglycerols, may also profoundly alter the activity of MGAT.

PMID- 9558326
TI  - Site-directed mutagenesis probing the catalytic role of arginines 165 and 166 of
      human cytomegalovirus protease.
AB  - Human cytomegalovirus (CMV) is a member of the Herpesviridae family of viruses
      that also includes herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster
      virus (VZV), human herpes virus-6, 7, and 8 (HHV-6, HHV-7, and HHV-8), and
      Epstein-Barr virus (EBV). Each member of this family encodes a serine protease
      that is a potential target for antiviral therapeutic intervention. We recently
      reported the crystal structure of CMV proteases [Qiu, X., Culp, J. S., DiLella,
      A. G., Hellmig, B., Hoog, S. S., Janson, C. A., Smith, W. W., and Abdel-Meguid,
      S. S. (1996) Nature 383, 275-279] and proposed that the highly conserved Arg165
      and Arg166 residues are involved in stabilizing the oxyanion intermediate in
      human herpes protease catalyzed reactions through the backbone NH and side chain,
      respectively. In the current study, site-directed mutagenesis was carried out to
      probe the catalytic function of these two amino acid residues. Substitution of
      Arg166 with an alanine has led to ablation of enzymatic activity without
      detectable change in CMV protease conformation, supporting suggestions from the
      crystal structure that Arg166 side chain plays a major role in catalysis. The
      wild-type has a Km = 138 +/- 17 microM and kcat = 19.9 +/- 1.1 min-1, while R166A
      has only residual activity, with a kcat = 0.012 +/- 0.001 min-1 and an unaltered
      Km = 145 +/- 18 microM. In the crystal structure, the side chain of Arg166 was
      shown previously to hold a water molecule that can act as a hydrogen-bond donor
      to the oxyanion and was thus proposed to stabilize the oxyanion intermediate.
      However, kinetic characterization of the mutant R165A only reveals a 2.7-fold
      lower activity than wild-type, with a Km = 166 +/- 19 microM and a kcat = 7.4 +/-
      0.4 min-1. These results confirm that Arg165 side chain is not involved in the
      stabilization of the oxyanion. It is likely that Arg165 only utilizes the
      backbone NH for catalysis as suggested by the crystal structure.

PMID- 9558328
TI  - Electrostatic stabilization in methionine aminopeptidase from hyperthermophile
      Pyrococcus furiosus.
AB  - The thermostability of methionine aminopeptidase from a hyperthermophile P.
      furiosus (PfMAP) was extremely high: the denaturation temperature was 106.2
      degreesC at pH 10.2. To explore the contribution of electrostatic interaction to
      the superior thermostability of PfMAP, the thermostability of PfMAP was examined
      by differential scanning calorimetry (DSC) in various salt concentrations in the
      acidic region far from the isoelectric point of PfMAP. (1) In 20 mM glycine
      buffer, the DSC curve of PfMAP exhibited a single peak. Transition temperatures
      (Tm) were lowered with decreasing pH from 4 to 3. The heat denaturation of PfMAP
      was not reversible. (2) Denaturation enthalpy (DeltaH) measured at different pHs
      linearly correlated with Tm up to 102 degreesC, suggesting that the denaturation
      heat capacity (DeltaCp) for PfMAP is constant up to 100 degreesC. DeltaCp was
      estimated to be 0.82 J K-1 g-1. (3) In the presence of 10-100 mM KCl at pH 3.2,
      two peaks appeared on the DSC curves. The first peak shifted to lower
      temperatures with increasing concentration of KCl and, oppositely, the second one
      to higher temperatures. It was found that the first and second peaks originated
      from the heat denaturation of the native form of PfMAP and the melting of the non
      native associated form having molten globule-like structure, respectively, judged
      from the CD spectra and ultracentrifugation analyses. This indicates the
      following: first, the attractive electrostatic interaction is an important factor
      in stabilizing the native form of PfMAP; second, the presence of KCl stimulates
      the formation of the molten globule-like state of PfMAP and stabilizes it. (4) In
      a comparison of the sequence and crystal structure of PfMAP, which has been
      recently determined (1xgs.pdb), with those of MAP from Escherichia coli (EcMAP),
      it was predicted that the extra four short-range ion pairs less than 3 A involved
      in PfMAP are crucial candidates as determinants for the superior thermostability
      of PfMAP.

PMID- 9558327
TI  - Identification of amino acid residues associated with modulation of flavin
      containing monooxygenase (FMO) activity by imipramine: structure/function studies
      with FMO1 from pig and rabbit.
AB  - The activity of the flavin-containing monooxygenase (FMO) can be modulated by a
      number of nitrogen-containing compounds in a manner that is both isoform and
      modulator-dependent. We now show that the direction (activation or inhibition)
      and extent of modulation can also be dependent on substrate concentration.
      Imipramine activates methimazole metabolism catalyzed by rabbit FMO1 or FMO2 at
      methimazole concentrations greater than 50 or 100 microM, respectively, and
      inhibits at lower methimazole concentrations. The extent of the activation
      increases as the substrate concentration increases, and the extent of inhibition
      increases as the substrate concentration decreases. With either inhibition or
      activation, the magnitude of the effect shows a similar, direct dependency on
      imipramine concentration. In contrast, imipramine inhibits the metabolism of
      methimazole catalyzed by pig FMO1 at all substrate concentrations. The structural
      basis for this unique ortholog difference between the responses of rabbit and pig
      FMO1 to imipramine was studied by random chimeragenesis and site-directed
      mutagenesis. Results with chimeras indicated that modulation of FMO1 activity by
      imipramine is controlled to a great extent by two areas of the FMO primary
      structure (residues 381-432 and 433-465). Four amino acids in these regions
      (positions 381, 400, 420 and 433) and one additional residue (position 186) were
      identified by site-directed mutagenesis as primary determinants of the imipramine
      response. When the residues at these positions in rabbit FMO1 are exchanged for
      the corresponding residues of pig FMO1, a mutant with the functional properties
      of pig FMO1 is produced. Our results suggest that the response of FMO1 to
      imipramine involves a distribution between two sites that is regulated by
      structural features that do not alter the overall binding. The inhibition
      observed, although it appears to be competitive, likely does not involve
      competition for a binding site since alteration of imipramine metabolism has no
      effect on the parameters of methimazole metabolism.

PMID- 9558329
TI  - Penicillin biosynthesis: energy requirement for tripeptide precursor formation by
      delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Acremonium
      chrysogenum.
AB  - In nonribosomal peptide formation by multifunctional enzymes, peptide synthetases
      catalyze the activation and directed condensation of amino acids. The peptide
      synthetase involved in penicillin biosynthesis (ACV synthetase) forms the
      tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine from the respective L
      amino acids and ATP. So far, the energy requirements for the nonribosomal process
      have not been clearly established. For ACV synthetase we show that ATP
      consumption depends on the reaction conditions employed. By simultaneously
      estimating peptide and AMP production by employing fluorescence detection and UV
      spectroscopy, respectively, we have determined the energy consumption with high
      accuracy. Under unfavorable reaction conditions more than 20 mol of ATP are
      consumed/mol of tripeptide formed, while optimal conditions permit the expected
      energy requirement of one ATP for each carboxyl group activation, corresponding
      to three ATP for tripeptide formation. The third ATP is required for the
      activation of L-valine to maintain the valyl-thioester stage for epimerization
      and peptide bond formation, and this high-energy bond is sacrificed by hydrolytic
      removal of the product. No extra energy is required for the directed transport in
      peptide elongation. Additional energy consumed has been traced to hydrolytic loss
      of activated intermediates, as has been shown by the analysis of incomplete
      reaction mixtures.

PMID- 9558331
TI  - Proteolytic fragments of the Alzheimer's disease associated presenilins-1 and -2
      are phosphorylated in vivo by distinct cellular mechanisms.
AB  - The majority of familial Alzheimer's disease mutations are linked to the recently
      cloned presenilin (PS) genes, which encode two highly homologous proteins (PS-1
      and PS-2). Full-length PS proteins undergo endoproteolytic cleavage within their
      hydrophilic loop domain resulting in the formation of C-terminal (CTF) and N
      terminal fragments (NTF). PS-2 was found to be phosphorylated as a full-length
      protein within its N-terminal domain. In contrast, PS-1 is phosphorylated
      selectively after proteolytic processing within its approximately 20 kDa CTF
      involving protein kinase C (PKC) and/or protein kinase A (PKA). We now have found
      that the CTF of the highly homologous PS-2 is also phosphorylated. Surprisingly,
      the PS-2 CTF is not phosphorylated by PKC or PKA. Instead, the PS-2 CTF is
      constitutively phosphorylated in vivo by serine/threonine protein kinases, which
      are independent of phorbol ester and intracellular cAMP. In vitro the large
      hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be
      phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC.
      Quantitative analysis of in vitro phosphorylation demonstrates the presence of
      two phosphorylation sites for CK-1 and a single site for CK-2. A deletion
      analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic
      sequence containing three potential phosphorylation sites for CKs (serines 327,
      330, and 335). These data suggest that CK type protein kinases phosphorylate the
      CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the
      potential phosphorylation sites are located directly adjacent to the recently
      identified caspase cleavage sites.

PMID- 9558330
TI  - Selective inactivation of parvulin-like peptidyl-prolyl cis/trans isomerases by
      juglone.
AB  - In contrast to FK506 binding proteins and cyclophilins, the parvulin family of
      peptidyl-prolyl cis/trans isomerases (PPIases; E.C. 5.2.1.8) cannot be inhibited
      by either FK506 or cyclosporin A. We have found that juglone, 5-hydroxy-1,4
      naphthoquinone, irreversibly inhibits the enzymatic activity of several
      parvulins, like the E. coli parvulin, the yeast Ess1/Ptf1, and human Pin1, in a
      specific manner, thus allowing selective inactivation of these enzymes in the
      presence of other PPIases. The mode of action was studied by analyzing the
      inactivation kinetics and the nature of products of the reaction of E. coli
      parvulin and its Cys69Ala variant with juglone. For all parvulins investigated,
      complete inactivation was obtained by a slow process that is characterized by
      pseudo-first-order rate constants in the range of 5.3 x 10(-)4 to 4. 5 x 10(-)3 s
      1. The inactivated parvulin contains two juglone molecules that are covalently
      bound to the side chains of Cys41 and Cys69 because of a Michael addition of the
      thiol groups to juglone. Redox reactions did not contribute to the inactivation
      process. Because thiol group modification was shown to proceed 5-fold faster than
      the rate of enzyme inactivation, it was considered as a necessary but not
      sufficient condition for inactivation. When measured by far-UV circular dichroism
      (CD), the rate of structural alterations following thiol group modification
      parallels exactly the rate of inactivation. Thus, partial unfolding of the active
      site of the parvulins was thought to be the cause of the deterioration of PPIase
      activity.

PMID- 9558332
TI  - Site-directed mutagenesis combined with chemical modification as a strategy for
      altering the specificity of the S1 and S1' pockets of subtilisin Bacillus lentus.
AB  - By combining site-directed mutagenesis with chemical modification, we have
      altered the S1 and S1' pocket specificity of subtilisin Bacillus lentus (SBL)
      through the incorporation of unnatural amino acid moieties, in the following
      manner: WT --> Cysmutant + H3CSO2SR --> Cys-SR, where R may be infinitely
      variable. A paradigm between extent of activity changes and surface exposure of
      the modified residue has emerged. Modification of M222C, a buried residue in the
      S1' pocket of SBL, caused dramatic changes in kcat/KM, of an up to 122-fold
      decrease, while modification of S166C, which is located at the bottom of the S1
      pocket and is partially surface exposed, effected more modest activity changes.
      Introduction of a positive charge at S166C does not alter kcat/KM, whereas the
      introduction of a negative charge results in lowered activity, possibly due to
      electrostatic interference with oxyanion stabilization. Activity is virtually
      unaltered upon modification of S156C, which is located toward the bottom of the
      S1 pocket and surface exposed and whose side chain is solvated. An unexpected
      structure-activity relationship was revealed for S166C-SR enzymes in that the
      pattern of activity changes observed with increasing steric size of R was not
      monotonic. Molecular modeling analysis was used to analyze this unprecedented
      structure-activity relationship and revealed that the position of the beta-carbon
      of Cys166 modulates binding of the P1 residue of the AAPF product inhibitor.

PMID- 9558333
TI  - Identification of a new all-trans-retinol metabolite produced through a new
      retinol metabolic pathway.
AB  - In vitro incubation of all-trans-retinol (atROL) with kidney homogenate from
      vitamin A-deficient and retinoic acid-supplemented (VAD-RAS) female rats produces
      a new retinol metabolite. Reverse-phase (RP) and normal-phase (NP) high
      performance liquid chromatography (HPLC) analysis showed that this metabolite
      coelutes with the unknown all-trans-retinol (atROL) metabolite previously found
      in the day 10 conceptus and kidneys of vitamin A-deficient rats maintained on all
      trans-retinoic acid (VAD-RA) and given 2 microg of [3H]atROL. Normal-phase (NP)
      HPLC purification of the metabolite collected from a RP HPLC column further
      separated the radiolabeled material into two components. The two isolated
      compounds have identical or very similar spectroscopic properties. Their nuclear
      magnetic resonance (1H NMR) and mass spectra (MS) indicated that they are
      isomers. Spectroscopic studies of the metabolites and their derivatives showed
      that they are nine-carbon fragments resulting from an oxidative cleavage of the
      side chain of atROL. The cleavage occurs at C-9, and the product is then oxidized
      to a keto group. The primary hydroxy group from atROL is preserved in the
      metabolite. A sulfide bridge is formed between C-11 and C-14, which interrupts
      the conjugation. The formation of the new metabolites, possessing a 2,5
      dihydrothiophene ring, is catalyzed by an enzyme(s) located in the cytosolic
      fraction of kidneys. The process represents a new retinol metabolic pathway;
      however, its biological significance is unknown.

PMID- 9558334
TI  - Inhibition kinetics and affinity labeling of bacterial squalene:hopene cyclase by
      thia-substituted analogues of 2, 3-oxidosqualene.
AB  - Five sulfur-containing analogues of 2,3-oxidosqualene (OS) were evaluated as
      inhibitors of squalene:hopene cyclase (SHC) from Alicyclobacillus acidocaldarius.
      In these analogues, sulfur replaces carbons at C-6, C-10, C-14, C-18, or C-19 of
      OS. Each analogue was a submicromolar inhibitor of SHC with IC50 values ranging
      from 60 to 570 nM. Enzyme inhibition kinetic analysis was performed using
      homogeneous recombinant A. acidocaldarius SHC. While analogues 9 (S-14, Ki = 109
      nM, kinact = 0.058 min-1) and 11 (S-19, Ki = 83 nM, kinact = 0.054 min-1) were
      time-dependent inhibitors of SHC, analogues 7 (S-6, Ki = 127 nM) and 8 (S-10, Ki
      = 971 nM) showed no time dependency with SHC. Analogue 10 (S-18) was the most
      potent inhibitor and showed time-dependent irreversible inhibition (Ki = 31 nM,
      kinact = 0.071 min-1). Kinetic analysis for the five analogues with purified rat
      liver OSLC was conducted to compare the vertebrate and prokaryotic enzymes.
      Affinity labeling experiments, using either [17-3H]10 or [22-3H]10 with crude and
      with pure recombinant SHC, clearly showed specific labeling. A single major
      radioactive band at 72 kDa on SDS-PAGE indicated that irreversible covalent
      modification of SHC had occurred. These results suggest that the presence of
      sulfur at C-18 of OS can interrupt the cyclization and that an intermediate
      partially cyclized cation may be captured by a nucleophilic residue of the SHC
      active site.

PMID- 9558335
TI  - An AP-1 site in the nerve growth factor promoter is essential for 1, 25
      dihydroxyvitamin D3-mediated nerve growth factor expression in osteoblasts.
AB  - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D,
      induces nerve growth factor (NGF) synthesis in a variety of different cell lines.
      The mechanism by which 1,25(OH)2D3 induces NGF, however, is poorly understood. We
      used a series of full-length and truncated NGF promoter-human growth hormone
      (hGH) reporter gene plasmids to investigate the mechanism of 1,25(OH)2D3-induced
      NGF expression in osteoblasts. Untransfected rat osteosarcoma cells (ROS 17/2.8)
      treated with 1,25(OH)2D3 showed a 2-fold increase in NGF expression compared to
      control cells. ROS 17/2.8 osteosarcoma cells were transfected with the NGF-hGH
      reporter plasmids and treated with 10(-)8 M 1,25(OH)2D3. The full-length NGF
      promoter (-1800 to +120)-hGH reporter construct showed an approximately 2-fold
      increase in hGH release. Plasmids with successive 5'-deletions showed enhanced
      hGH expression in treated cells and control cells. A similar series of NGF
      promoter-hGH reporter gene constructs, lacking the AP-1 site located within the
      first intron of the NGF gene, were also transiently transfected into ROS 17/2.8
      cells. When these cells were treated with the same dose of 1,25(OH)2D3, no
      increase in hGH expression was seen compared to control cells, demonstrating that
      this AP-1 site is essential for 1,25(OH)2D3-mediated NGF up-regulation. Since
      1,25(OH)2D3 is known to activate the transcription of several genes through its
      interaction with the vitamin D receptor (VDR), we performed a series of gel
      electrophoretic mobility shift assays to determine if the VDR binds directly to
      the AP-1 sequence. No evidence of VDR binding, either as a homodimer or as a
      heterodimer, to the AP-1 sequence was observed. Treatment of ROS 17/2.8 cells
      with 1,25(OH)2D3, however, resulted in an increase in AP-1 binding activity;
      however, no significant changes in c-jun and c-fos levels were observed. Our data
      show that in osteoblasts, 1,25(OH)2D3 induces NGF expression indirectly by
      increasing AP-1 binding activity.

PMID- 9558336
TI  - Ligand binding and covalent structure of an oxygen-binding heme protein from
      Rhodobacter sphaeroides, a representative of a new structural family of c-type
      cytochromes.
AB  - The amino acid sequence of an oxygen-binding heme protein (SHP) from Rhodobacter
      sphaeroides has been determined. The cysteines, which bind the single heme group
      in the 112-residue protein, are located at positions 43 and 46. SHP is similar in
      size to the large membrane-bound form of the class I cytochrome c5 of Azotobacter
      vinelandii (116 residues) and in the location of the heme binding site at
      positions 48 and 51. Two extra cysteines in SHP (residues 89 and 97) are located
      in positions similar to those of cytochrome c5 (residues 98 and 101) and form a
      disulfide bridge in both proteins. In total, four regions of alpha-helix are
      predicted, covering 46% of the protein, which is comparable to that in other
      small cytochromes. SHP is thus distantly related to small class I c-type
      cytochromes but is representative of a distinct family by virtue of its high-spin
      nature, the lack of a strong sixth ligand, and its capacity to bind oxygen.
      Potentially, the most important characteristic of SHP is its ability to
      transiently bind oxygen during autoxidation, which occurs with a half-life of 3
      min with a 4-fold excess of O2. SHP also binds carbon monoxide, azide, and
      cyanide. The kinetics of reduction by free flavins indicate that SHP is less
      reactive than other class I cytochromes c and that the heme is less accessible to
      solvent. There is localized positive charge (+3) at the site of reduction of SHP,
      although the overall protein charge is -2. This may account in part for the
      ability of SHP to bind anions.

PMID- 9558337
TI  - Hepatocyte growth factor/scatter factor has distinct classes of binding site in
      heparan sulfate from mammary cells.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a heparan sulfate (HS)
      binding growth factor and morphogen for mammary epithelial cells that is produced
      by mammary stromal fibroblasts. HS chains, purified as peptidoglycans from a
      panel of cell lines representative of the ductal epithelial cell (Huma 123), the
      myoepithelial cell (Huma 109), the stromal fibroblast (Rama 27), and malignant
      mammary epithelial cells (MCF-7 and ZR-75), were used in a biosensor-based assay
      to identify the classes of HGF/SF-binding sites in the polysaccharide chains. At
      least three distinct binding sites were identified. One site exhibits fast
      association and fast dissociation kinetics [kass (1.4-7.7) x 10(6) M-1 s-1; kdiss
      0. 0032-0.0096 s-1] and is present on the HS from benign Huma 123 epithelial
      cells, Huma 109 myoepithelial-like cells, and ZR-75 malignant cells. The second
      binding site, found on HS from the malignant MCF-7 cells, has slower HGF/SF
      binding kinetics (kass 0.20 x 10(6) M-1 s-1; kdiss 0.00055 s-1). The third
      binding site possesses fast association and slow dissociation kinetics (kass 1.1
      x 10(6) M-1 s-1; kdiss 0.00020 s-1) and was found on the HS isolated from the
      culture medium of the Huma 123 benign epithelial cells. The first and second
      binding sites have a similar Kd, 1-3 nM, while the third binding site has a
      considerably higher affinity for HGF/SF (Kd 200 pM). The three binding sites seem
      to be mutually exclusive, since each sample of HS possessed just one of the
      sites.

PMID- 9558338
TI  - Nonproteolytic incorporation of protein ligands into human alpha 2-macroglobulin:
      implications for the binding mechanism of alpha 2-macroglobulin.
AB  - alpha 2-Macroglobulin (alpha 2M) is a complex tetrameric protein of 718 kDa. In
      native alpha 2M, each of the four subunits contains a thiol ester between the
      side chains of Cys949 and Gln952. Cleavage of the thiol ester with small
      nucleophiles destabilizes the native conformation and causes a major
      conformational change in alpha 2M, which leads to exposure of receptor binding
      sites and a change in electrophoretic mobility. Recently it has been shown that
      nucleophilic cleavage of the four thiol esters in alpha 2M is a reversible
      process with energy requirements dependent on the nucleophile [Gron, H.,
      Thogersen, I. B., Enghild, J. J., and Pizzo, S. V. (1996) Biochem. J. 318, 539
      545]. The present study is a further investigation of the properties of alpha 2M
      with cleaved thiol esters and the potential for incorporation of protein ligands
      at the site of the thiol ester. The thiol ester in alpha 2M was cleaved by NH3.
      After removal of excess NH3, the alpha 2M derivative was incubated with excess
      protein ligand (hen egg lysozyme or bovine insulin) at 23, 37, or 50 degreesC,
      leading to covalent incorporation of the ligands in alpha 2M as analyzed by SDS
      PAGE, gel filtration, and centrifugal microfiltration. Receptor binding studies
      and native pore-limit PAGE confirmed that the alpha 2M derivatives with ligand
      incorporated remained in the receptor-recognized, "fast" migrating conformation.
      This is the first demonstration of nonproteolytic, covalent incorporation of
      protein ligands into receptor-recognized alpha 2M.

PMID- 9558339
TI  - Recognition properties of a sequence-specific DNA binding antibody.
AB  - A sequence-specific DNA-binding antibody was previously generated by
      incorporating a 17 amino acid alpha-helix from the DNA-binding domain of the
      transcription factor TFEB into the HCDR3 site of a recombinant human Fab
      fragment. The recombinant DNA-binding antibody, called Fab-E box, binds the TFEB
      recognition sequence CACGTG (an E box site) with a 5-10-fold lower affinity than
      TFEB. Here, we have determined the precise kinetics of interaction of Fab-E box
      with DNA and show that the lower affinity of Fab-E box relative to TFEB for E box
      DNA is due to a higher dissociation rate. DNase I protection assays show Fab-E
      box physically interacts with one half-site of the E box. Additional DNA target
      sites of Fab-E box were identified by DNase I protection assays. A compilation of
      these binding sites indicates that the recognition elements for Fab-E box binding
      include a half-site of the E box, CAW, with an 8 bp consensus sequence identified
      as YNYYCAWW. Thus, the DNA determinants for Fab-E box recognition extend beyond
      one-half site of the E box sequence, with preferences for pyrimidines and A+T
      rich sequences in the 5' and 3' outer regions of the binding site, respectively.
      Apparent dissociation constants of Fab-E box for a subset of these target DNA
      sequences are 5-10-fold greater than the DNA-binding affinity of the antibody
      with the E box site. Therefore, these results identify important DNA specificity
      determinants for high-affinity binding by Fab-E box.

PMID- 9558340
TI  - Properties of overlapping EREs: synergistic activation of transcription and
      cooperative binding of ER.
AB  - We have designed a novel estrogen-responsive unit, overERE, which consists of two
      overlapping ERE separated by 5 bp (center-to-center). In gel retardation assays,
      this sequence forms a low-mobility complex that migrates like an estrogen
      receptor tetramer. The receptor-overERE complex was specific and was supershifted
      by anti-ER H222 antibodies. Dose response studies showed that the formation of
      the receptor tetramer-overERE complex was cooperative. Truncated receptors were
      used to assess the contribution of the receptor domains. Deletion of the E domain
      of the ER prevented the formation of an ER-tetramer complex, which reflects a
      novel function of this receptor domain. In transfection experiments, 17-beta
      estradiol activated transcription from an overERE-containing promoter 4-6 times
      better than from an ERE-containing promoter. This synergistic effect was observed
      using either the natural hormone (17-beta-estradiol) or xenoestrogens (phenol
      red, chlordane). We conclude that two overlapping estrogen-responsive elements
      can elicit synergistic induction of transcription.

PMID- 9558341
TI  - Saccharomyces cerevisiae possesses two functional homologues of Escherichia coli
      endonuclease III.
AB  - We previously identified two distinct genes of Saccharomyces cerevisiae
      redoxyendonuclease (SCR1 and SCR2) which possess a high degree of sequence
      similarity to Escherichia coli endonuclease III [Augeri, L., Lee, Y. M., Barton,
      A. B., and Doetsch, P. W. (1997) Biochemistry 36, 721-729]. The proteins encoded
      by SCR1 and SCR2 were overexpressed in E. coli and purified to apparent
      homogeneity. Both proteins recognized and cleaved DNA substrates containing
      dihydrouracil, 2,6-diamino-4-hydroxy-5N-methylformamidopyrimidine (FaPy-7-MeGua),
      and abasic sites but not DNA substrates containing uracil or 8-oxoguanine.
      Purified Scr2, but not Scr1, possesses spectral properties which indicate the
      presence of an iron-sulfur center. Kinetic parameters for Scr1 and Scr2 were
      determined by using an oligonucleotide containing a single dihydrouracil.
      Analysis of the deduced amino acid sequences of Scr1 and Scr2 suggests that Scr2
      bears an iron-sulfur motif, while Scr1 does not have this motif. However, Scr1
      has a long, positively charged N-terminus that could be a mitochondrial transit
      sequence. Targeted gene disruption of SCR1 and SCR2 produced a double mutant that
      had no detectable enzymatic activity against the dihydrouracil-containing
      substrate. Northern blot analysis showed that SCR1 was induced by menadione, but
      SCR2 was not. These results indicate that although Scr1 and Scr2 are both
      functional homologues of E. coli endonuclease III, they differ from each other
      with respect to their amino acid sequences and inducibility by DNA damaging
      agents, suggesting that their precise biological roles may be different.

PMID- 9558342
TI  - Role of base G-2 of pre-tRNAfMet in cleavage site selection by Escherichia coli
      RNase P in vitro.
AB  - In this study, a protocol for the purification of fully active Escherichia coli
      RNase P holoenzyme from a strain overproducing both the C5 protein and the M1 RNA
      components is described. A total of 0. 8 mg of homogeneous enzyme, with a 1:1
      protein/RNA subunit stoichiometry, was recovered from a 1 L bacterial culture. In
      addition, a convenient and reliable method based on capillary gel electrophoresis
      was developed to measure initial rates of pre-tRNA maturation by RNase P. Using
      these tools, the kinetic parameters of cleavage by RNase P of various mutants of
      pre-tRNAfMet showing maturation defects in vivo [Meinnel and Blanquet (1995) J.
      Biol. Chem. 270, 15906-15914] were investigated in vitro and the locations of
      cleavage sites were determined from the length of the various products of the
      reaction. The nucleotide at position -2 of pre-tRNAfMet is shown to be important
      only in the selection of the cleavage site, whereas it has no role in the
      efficiency of the reaction. It is concluded that base G-2 acts as an
      antideterminant by preventing an alternative cleavage by RNase P. In addition,
      the presence of G-2 alone is enough to fully compensate for the lack of a G at
      position +1 of pre-tRNAfMet.

PMID- 9558344
TI  - Unexpected electrophoretic migration of RNA with different 3' termini causes a
      RNA sizing ambiguity that can be resolved using nuclease P1-generated sequencing
      ladders.
AB  - It has been widely believed that the electrophoretic migration difference of
      otherwise identical RNAs with a P versus OH terminus would be the same as occurs
      for DNA, a fairly reproducible approximately 1/2 nucleotide (nt) offset. RNA with
      a 5'-OH indeed migrates </=1 nt slower than if it had a 5'-P. Surprisingly,
      however, RNA with a 3'-OH terminus (generated by many cellular RNases of
      interest) migrates anywhere from approximately 1/4 to approximately 2 nts slower
      than the otherwise identical molecule with a 3'-P or 2', 3'-cyclic-P terminus (as
      present on standard RNase-generated sequencing ladders). This previously
      unrecognized variability in electrophoretic migration offset causes a 1-2 nt
      ambiguity in a commonly used method of RNA size determination. We also show two
      ways to overcome this problem and enable rigorous sizing of 3'-OH terminating
      RNAs. Most convenient is to use sequencing standards generated by nuclease P1,
      which is generally sequence-nonspecific but we show becomes G-specific or A
      preferential under certain reaction conditions.

PMID- 9558343
TI  - Expression, purification, and initial kinetic characterization of the large
      subunit of the human mitochondrial DNA polymerase.
AB  - Faulty replication of the human mitochondrial genome is thought to be the cause
      of many diseases; moreover, the low selectivity of the mitochondrial DNA
      polymerase has been implicated as the cause of many side effects observed in the
      treatment of viral infections such as HIV. To better understand how the
      mitochondrial genome is replicated, we cloned a cDNA encoding the large subunit
      of human DNA polymerase gamma, the enzyme that replicates the mitochondrial
      genome. The large subunit was recombinantly expressed and purified to near
      homogeneity. The purified enzyme demonstrated both polymerase and 3'-5'
      exonuclease activity. The purified protein was examined in single nucleotide
      incorporation assays, demonstrating that the enzyme had a maximum polymerization
      rate of 3.5 s-1 and a dissociation rate from the DNA substrate of 0.03 s-1,
      affording a calculated processivity of 116. The dissociation constants for the
      enzyme binding to DNA and nucleoside triphosphate were 39 nM and 14 microM,
      respectively. The 3'-5' exonuclease rate was measured at 0. 18 s-1. Though the
      slow rate of polymerization suggests that the large subunit of human DNA
      polymerase gamma may require accessory factors to increase its processivity of
      polymerization, the kinetic parameters indicate that the large subunit of DNA
      polymerase gamma could replicate the mitochondrial genome in a physiologically
      relevant time frame. This study provides the initial characterization of the
      large subunit of DNA polymerase gamma and establishes the baseline for
      examination of the effects of accessory proteins such as the putative small
      subunit.

PMID- 9558345
TI  - The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to
      DNA sequences containing an AAC motif and to distorted DNA structures.
AB  - The c-Abl tyrosine kinase protein is implicated in the signaling pathway as well
      as in transcription, DNA repair, apoptosis, and several other vital biological
      processes essential for cell proliferation or differentiation. The interaction of
      c-Abl with DNA is important for some of these functions, but the exact nature of
      this interaction is still a matter of controversy. The present study addresses
      the DNA-binding properties of the human c-Abl protein. Using CASTing experiments,
      the consensus binding site 5'-AA/CAACAAA/C was determined. The central highly
      conserved AAC triplet appears to constitute the crucial core element in the
      binding sequences of the c-Abl protein. The c-Abl DNA-binding domain recognizes
      specific sequences and interacts with deformed DNA structures such as four-way
      junctions and bubble DNA containing a large single-stranded loop, as determined
      by electromobility shift assay, melting temperature studies, and binding to
      specific oligonucleotides covalently linked to beads. Additional competition
      experiments suggest that the interaction mainly involves contacts within the
      minor groove of the double helix. The DNA-binding properties of c-Abl are
      reminiscent of those of high-mobility group (HMG)-like proteins such as LEF-1 and
      SRY. However, the circular permutation and ring closure assays and DNA unwinding
      experiments reveal that, unlike HMGs, c-Abl does not bend its target sequence. In
      addition, it is shown that the protein potentiates the DNA relaxation activity of
      topoisomerase I. These findings indicate that the interaction of c-Abl with DNA
      is both sequence-selective and structure-dependent.

PMID- 9558346
TI  - Dimerization of MoMuLV genomic RNA: redefinition of the role of the palindromic
      stem-loop H1 (278-303) and new roles for stem-loops H2 (310-352) and H3 (355
      374).
AB  - Genomic RNAs from retroviruses are packaged as dimers of two identical RNA
      molecules. In Moloney murine leukemia virus, a stem-loop structure (H1) located
      in the encapsidation domain Psi (nucleotides 215-564) was postulated to trigger
      RNA dimerization through base pairing between auto complementary sequences. The
      Psi domain also contains two other stem-loop structures (H2 and H3) that are
      essential for RNA packaging. Since it was suspected than H1 is not the only
      element involved in RNA dimerization, we systematically investigated the
      dimerization capacity of several subdomains of the first 725 nucleotides of
      genomic RNA. The efficiency of dimerization of the various RNAs was estimated by
      measuring their apparent dissociation constants, and the specificity was tested
      by competition experiments. Our results indicate that the specificity of
      dimerization of RNA nucleotides 1-725 is driven by motifs H1-H3 in domain Psi. To
      define the relative contributions of these elements, RNA deletion mutants
      containing different combinations of H1-H3 were constructed and further analyzed
      in competition and kinetic experiments. Our results confirm the importance of H1
      in triggering dimerization and shed new light on the mechanism of dimerization.
      H1 is required to provide a stable dimer, probably through the formation of
      extended intermolecular interactions. However, H1-mediated association is a slow
      process that is kinetically enhanced by H3, and to a lesser extent by H2. We
      suggest that they facilitate the recognition between the two RNAs, most likely
      through their conserved GACG loops. Our results reinforce the idea that
      dimerization and packaging are two closely related processes.

PMID- 9558347
TI  - Spectroscopic, kinetic, and electrochemical characterization of heterologously
      expressed wild-type and mutant forms of copper-containing nitrite reductase from
      Rhodobacter sphaeroides 2.4.3.
AB  - We report the development of a high-yield heterologous expression system for the
      copper-containing nitrite reductase from a denitrifying variant of Rhodobacter
      sphaeroides. Typical yields of wild-type protein are 20 mg L-1, which can be
      fully loaded with copper. Nitrite reductase contains an unusual blue-green Type 1
      copper center with a redox/electron transfer function and a nearby Type 2 center
      where nitrite binds and is reduced to nitric oxide. The wild-type enzyme was
      characterized by: (1) its blue-green Type 1 optical spectrum; (2) its EPR
      spectrum showing rhombic character to its Type 1 center and nitrite perturbation
      to its Type 2 center; (3) its 247-mV Type 1 midpoint potential which is low
      relative to other Type 1 centers; and (4) its kinetics as measured by both steady
      state and stopped-flow methods. The Type 2 copper reduction potential as
      monitored by EPR in the absence of nitrite was below 200 mV so that reduction of
      the Type 2 center by the Type 1 center in the absence of nitrite is not
      energetically favored. The mutation M182T in which the methionine ligand of Type
      1 copper was changed to a threonine resulted in a blue rather than blue-green
      Type 1 center, a midpoint potential that increased by more than 100 mV above that
      of the wild-type Type 1 center, and a somewhat reduced nitrite reductase
      activity. The blue color and midpoint potential of M182T are reminiscent of
      plastocyanin, but the Type 1 cupric HOMO ground-state electronic g value and
      copper hyperfine properties of M182T (as well as cysteine and histidine ENDOR
      hyperfine properties; see next paper) were unchanged from those of the blue-green
      native Type 1 center. His287 is a residue in the Type 2 region whose imidazole
      ring was thought to hydrogen bond to the Type 2 axial ligand but not directly to
      Type 2 copper. The mutation H287E resulted in a 100-fold loss of enzyme activity
      and a Type 2 EPR spectrum (as well as ENDOR spectra; see next paper) which were
      no longer sensitive to the presence of nitrite.

PMID- 9558348
TI  - Electronic structural information from Q-band ENDOR on the type 1 and type 2
      copper liganding environment in wild-type and mutant forms of copper-containing
      nitrite reductase.
AB  - Q-band ENDOR elucidated proton and nitrogen hyperfine features to provide spin
      density information at ligands of blue-green Type 1 and catalytic Type 2 copper
      centers in nitrite reductase. The blue-green Type 1 center of nitrite reductase
      has a redox, electron-transfer role, and compared to the blue center of
      plastocyanin, it has the following structural differences: a shortened Cu-Smet
      bond length, a longer Cu-Scys bond length, and altered ligand-copper-ligand bond
      angles (Adman, E. T., Godden, J. W., and Turley, S. (1995) J. Biol. Chem. 270,
      27458-27474). The hyperfine couplings of the two Type 1 histidine (N delta)
      ligands showed a larger percentage difference from each other in electron spin
      density than previously reported for other blue Type 1 proteins, while the
      cysteine beta-proton hyperfine couplings, a measure of unpaired p pi spin density
      on the liganding cysteine sulfur, showed a smaller electron spin density. A
      mutation of the Type 1 center, M182T, having the copper-liganding Met182
      transformed to Thr182, caused the center to revert to an optically "blue" center,
      raised its redox potential by approximately 100 mV, and led to the loss of
      activity (prior paper). Surprisingly, in M182T there was no change from native
      Type 1 copper either in the histidine or cysteine hyperfine couplings or in g
      values and Cu nuclear hyperfine couplings. The conclusion is that the optical and
      redox alterations due to changed Type 1 methionine ligation need not be
      concurrent with electron spin delocalization changes in the HOMO as reported from
      its essential cysteine and histidines. A detailed picture of the nitrogen
      couplings from the three histidine (N epsilon) ligands of the Type 2 center
      indicated a substantial ( approximately 200%) electronic hyperfine inequivalence
      of one of the histidine nitrogens from the other two within the Type 2 HOMO and
      thus provided evidence for electronic distortion of the Type 2 site. In the
      presence of the nitrite substrate, hyperfine couplings of all histidines
      diminished. We suggest that this nitrite-induced decreased covalency would
      correlate with an increased Type 2 redox potential to assist electron transfer to
      the Type 2 center. Dipole-coupled, angle-selected exchangeable proton features,
      observed over a range of g values, predicted a ligand-water proton distance of
      2.80 A from copper, and these water protons were eliminated by nitrite. His287 is
      not a Type 2 ligand but is positioned to perturb an axial water or a nitrite of
      Type 2 copper. In the presence of nitrite the mutant H287E showed no evidence for
      the loss of water protons and no diminished ligand histidine covalency. H287E has
      vastly diminished activity (prior paper), and the ENDOR information is that NO2-
      does not bind to Type 2 copper of H287E. In summary, the electronic information
      from this study of native and suitably chosen mutants provided a test of the
      highest occupied molecular orbital (HOMO) wave function at Type 1 and Type 2
      coppers and an intimate electronic insight into functional enzymatic properties.

PMID- 9558349
TI  - NADPH-flavodoxin reductase and flavodoxin from Escherichia coli: characteristics
      as a soluble microsomal P450 reductase.
AB  - In addition to their endogenous roles as an activation system for various
      Escherichia coli metabolic pathways, the soluble flavoproteins flavodoxin (Fld)
      and NADPH-flavodoxin (ferredoxin) reductase (Fpr) can serve as an electron
      transfer system for microsomal cytochrome P450s. Furthermore, since Fld and Fpr
      are structurally similar to the functional domains (FMN binding and NADPH/FAD
      binding domains, respectively) of NADPH-cytochrome P450 reductases (P450
      reductases), these bacterial proteins represent a potentially useful model system
      for eukaryotic P450 reductases. Here we delineate similarities and differences
      between the E. coli Fpr-Fld system and rat P450 reductase as electron donors to
      bovine 17alpha-hydroxylase/17,20-lyase P450 (P450c17). Importantly, recombinant
      Fpr, in combination with recombinant Fld, supports both the hydroxylase and lyase
      activities of P450c17 to the same proportional extent (hydroxylase-to-lyase
      ratio) as does P450 reductase. Maximum P450c17 turnover [5-6 mol of 17alpha-OH
      progesterone (mol of P450c17)-1 min-1] was achieved using a large molar excess
      (50-100-fold over P450c17) of a 1:1 ratio of Fpr-Fld, although this rate was an
      order of magnitude less than the maximal P450 reductase-supported activity. Using
      these conditions, we have examined the effects of increasing ionic strength and
      the presence of cytochrome b5 (b5) on these two systems. Critical Fld-P450c17
      electrostatic interactions are disrupted at moderate ionic strength (>100 mM
      NaCl) as evidenced by significant inhibition (>50%) of Fpr-Fld-supported P450c17
      activity while much higher ionic strength (300 mM NaCl) is required to disrupt
      P450 reductase-P450c17 interactions to the same extent. Interestingly, cytochrome
      b5 was found to dramatically inhibit both P450 reductase- and Fpr-Fld-supported
      P450c17 progesterone 17alpha-hydroxylase activity while in contrast 17alpha-OH
      pregnenolone lyase activity was stimulated by b5. Investigation of the fate of
      reducing equivalents from NADPH added to Fpr under aerobic conditions revealed
      that the majority of the protein-bound FAD of Fpr is converted to the
      hydroquinone form. In constrast, the FMN of Fld is reduced by Fpr to a stable
      blue, neutral semiquinone which serves as the predominant electron donor to
      P450c17 in reconstitution assays. Thus, while the Fpr-Fld system and P450
      reductase are fundamentally different with respect to their electrostatic
      interactions with P450c17, their ability to support maximal P450c17 turnover, and
      the FMN redox states (one-electron-reduced for Fld and two-electron-reduced for
      P450 reductase) capable of transferring electrons to microsomal cytochrome P450s,
      these differences do not appear to influence the relative catalytic efficiency of
      the P450c17 hydroxylase and lyase reactions.

PMID- 9558350
TI  - The flavoprotein component of the Escherichia coli sulfite reductase: expression,
      purification, and spectral and catalytic properties of a monomeric form
      containing both the flavin adenine dinucleotide and the flavin mononucleotide
      cofactors.
AB  - The flavoprotein component (SiR-FP) of the sulfite reductase from Escherichia
      coli is an octamer containing one FAD and one FMN per polypeptide chain. SiR
      FP60, a SiR-FP fragment starting with alanine-52, was overexpressed in E. coli
      and purified as a monomer. The N-terminal part of the native protein contains
      thus all the determinants required for the polymerization. SiR-FP60 retains both
      FAD and FMN with comparable contributions of the two flavins and the catalytic
      properties of SiR-FP. Thus, SiR-FP60 can be considered as a reliable simplified
      model of the sulfite reductase flavoprotein component. The formation and the
      stabilization of the neutral FMN semiquinone is thermodynamically favorable in
      SiR-FP60 upon reduction with photoreduced deazaflavin, dithionite, or NADPH.
      Generation of FMNH* is explained from a disproportionation of electrons between
      the reduced and oxidized FMN moieties during an intermolecular reaction, as shown
      with SiR-FP23, the FMN-binding domain of SiR-FP. The neutral FAD semiquinone can
      be observed only within SiR-FP43, the isolated FAD-binding domain. NADPH was used
      as a titrant or in excess to demonstrate that electron transfer is possible only
      because the FMN cofactor is coupled to FAD as an electron acceptor in the
      protein. The electron distribution within the various reduced forms of SiR-FP60
      has been compared with that of the reduced forms of cytochrome P450 reductase,
      bacterial cytochrome P450, and nitric-oxide synthase. Despite the conservation of
      the bi-flavin-domain structure between these proteins over evolutionary time,
      each of them provides significantly different flavin reactivities.

PMID- 9558352
TI  - High hydrostatic pressure can reverse aggregation of protein folding
      intermediates and facilitate acquisition of native structure.
AB  - The present work demonstrates that high hydrostatic pressure can increase protein
      folding by reducing nonspecific aggregation. Protein aggregation is one of the
      main side reactions that competes with protein folding, and it typically results
      from interactions among partially folded intermediates. It is known that
      oligomeric proteins can be dissociated by the application of high hydrostatic
      pressure. Since protein aggregates can be described as nonspecific protein
      oligomers, it can be predicted that they can be completely or partially
      dissociated by pressure. The enzyme rhodanese is prone to slow aggregation in 3.9
      M urea, and it is widely used as a model for the folding of a protein which
      readily aggregates. In the present study, it was demonstrated that this
      aggregation process could be completely reversed under high hydrostatic pressure.
      Release of the pressure led to renewed protein aggregation. In addition, it was
      demonstrated that refolding of urea-denatured rhodanese at 2 kbar pressure led to
      an increased yield of the native enzyme. The final recovery was increased up to
      approximately 25% in contrast to approximately 5% recovery observed under ambient
      pressure. The recovery can be further increased in the presence of 4 M glycerol,
      where 56% of the protein was recovered by treatment with high pressure. These
      observations suggest that some protein aggregation can be limited without the use
      of chemical additives, and they show that the pressures needed to maintain
      solubility are considerably less than those typically required for dissociation
      of specific oligomers and unfolding of polypeptide chains.

PMID- 9558351
TI  - Bacterial expression of a mitochondrial cytochrome c. Trimethylation of lys72 in
      yeast iso-1-cytochrome c and the alkaline conformational transition.
AB  - Saccharomyces cerevisiae iso-1-cytochrome c has been expressed in Escherichia
      coli by coexpression of the genes encoding the cytochrome (CYC1) and yeast
      cytochrome c heme lyase (CYC3). Construction of this expression system involved
      cloning the two genes in parallel into the vector pUC18 to give the plasmid
      pBPCYC1(wt)/3. Transcription was directed by two promoters, Lac and Trc, that
      were located upstream from CYC1. Both proteins were expressed in the cytoplasm of
      E. coli cells harboring the plasmid. Semianaerobic cultures grown in a fermentor
      produced 15 mg of recombinant iso-1-cytochrome c per liter of culture. Attempts
      to increase production by addition of IPTG suppressed the number of copies of the
      CYC1 gene within the population. Wild-type iso-1-cytochrome c expressed with
      pBPCYC1(wt)/3 in E. coli was compared to the same protein expressed in yeast. At
      neutral pH, the two proteins exhibit indistinguishable spectroscopic and physical
      (Tm, Em') characteristics. However, electrospray mass spectrometry revealed that
      the lysyl residue at position 72 is not trimethylated by E. coli as it is by S.
      cerevisiae. Interestingly, the pKa of the alkaline transition of the protein
      expressed in E. coli is approximately 0.6 pKa unit lower than that observed for
      the cytochrome expressed in yeast (8.5-8.7). 1H NMR spectroscopy of the
      bacterially expressed cytochrome collected at high pH revealed the presence of a
      third alkaline conformer that is not observed in the corresponding spectrum of
      the cytochrome expressed in yeast. These observations suggest that Lys72 can
      serve as an axial ligand to the heme iron of alkaline iso-1-ferricytochrome c if
      it is not modified posttranscriptionally to trimethyllysine.

PMID- 9558353
TI  - Effects of various imidazole ligands on heme conformation in endothelial nitric
      oxide synthase.
AB  - We have evaluated the influence of a series of substituted imidazoles on the heme
      structure of endothelial nitric oxide synthase (eNOS). Optical, MCD, and EPR
      spectra reveal widely differing effects on heme spin state and geometry. 1
      Substituted imidazoles always yield low-spin heme complexes, but the size of the
      2- and 4-substituent influences their structural effects on the heme. Methyl
      substituents lead to low-spin complexes while the bulky phenyl group yields high
      spin complexes. The only exception to this behavior is provided by 2
      aminoimidazole. Although this compound has three functional groups which can
      serve as an axial ligand to the heme, its binding to eNOS leads to a pure high
      spin complex. This result can only be interpreted as due to a direct binding of 2
      aminoimidazole to the guanidine binding subdomain of L-arginine. MCD spectra also
      imply that an O-ligand is present in the low-spin resting eNOS, while EPR data
      reveal the presence of two low-spin heme complexes in resting eNOS and its
      imidazole complexes. EPR also distinguishes four different high-spin forms of
      eNOS generated by different imidazole analogues. This series of ligands promises
      to be useful in probing the subtle structural difference among the active sites
      of three NOS isozymes and in developing selective inhibitors to these important
      enzymes.

PMID- 9558354
TI  - Context-dependent nature of destabilizing mutations on the stability of FKBP12.
AB  - The context-dependent nature in which mutations affect protein stability was
      investigated using the FK506-binding protein, FKBP12. Thirty-four mutations were
      made at sites throughout the protein, including residues located in the
      hydrophobic core, the beta-sheet, and the solvent-exposed face of the alpha
      helix. Urea-induced denaturation experiments were used to measure the change in
      stability of the mutants relative to that of the wild type (Delta DeltaGU-F). The
      results clearly show that the extent of destabilization, or stabilization, is
      highly context-dependent. Correlations were sought in order to link Delta DeltaGU
      F to various structural parameters. The strongest correlation found was between
      Delta DeltaGU-F and N, the number of methyl(ene) groups within a 6 A radius of
      the group(s) deleted. For mutations of buried hydrophobic residues, a correlation
      coefficient of 0.73 (n = 16,where n is the number of points) was obtained. This
      increased to 0.81 (n = 24) on inclusion of mutations of partially buried
      hydrophobic residues. These data could be superimposed on data obtained for other
      proteins for which similarly detailed studies have been performed. Thus, the
      contribution to stability from hydrophobic side chains, independent of the extent
      to which a side chain is buried, can be estimated quantitatively using N. This
      correlation appears to be a general feature of all globular proteins. The effect
      on stability of mutating polar and charged residues in the alpha-helix and beta
      sheet was also found to be highly context-dependent. Previous experimental and
      statistical studies have shown that specific side chains can stabilize the N-caps
      of alpha-helices in proteins. Substitutions of Ile56 to Thr and Asp at the N-cap
      of the alpha-helix of FKBP12, however, were found to be highly destabilizing.
      Thus, the intrinsic propensities of an amino acid for a particular element of
      secondary structure can easily be outweighed by tertiary packing factors. This
      study highlights the importance of packing density in determining the
      contribution of a residue to protein stability. This is the most important factor
      that should be taken into consideration in protein design.

PMID- 9558355
TI  - Biochemical and physical characterization of the active FAD-containing form of
      nitroalkane oxidase from Fusarium oxysporum.
AB  - Nitroalkane oxidase from Fusarium oxysporum catalyzes the oxidation of
      nitroalkanes to aldehydes with production of nitrite and hydrogen peroxide. The
      enzyme has a molecular weight of 47 955 +/- 39, as determined by MALDI-TOF mass
      spectrometry; under nondenaturing conditions, the aggregation state of the enzyme
      is best described by a tetramer-dimer self-associating model, with an association
      constant of (8.5 +/- 4.4) x 10(6) M-1 (pH 7.0 and 4 degreesC). The amino acid
      composition and the N-terminal amino acid sequence do not match any known protein
      or open reading frame. The inactive 5-nitrobutyl-1,5-dihydroflavin found in the
      enzyme as purified was converted to FAD, allowing characterization of the active
      FAD-containing enzyme. With nitroethane as substrate, the Vmax and Km values are
      655 +/- 45 min-1 and 2.9 +/- 0.5 mM at pH 8.0 and 30 degreesC, respectively. One
      mole of FAD per mole of monomer enzyme is required for catalysis. No activity can
      be detected with amino acids or alpha-hydroxy acids as substrates. Reversible
      removal of the FAD cofactor yields inactive enzyme. The properties of the FAD
      cofactor in nitroalkane oxidase are within the range described for other
      oxidases. The UV-visible absorbance spectrum of the active enzyme shows maxima at
      446, 384, and 274 nm; the extinction coefficient at 446 nm is 11.7 mM-1 cm-1. The
      neutral form of the flavin semiquinone, with maxima at 536 and 342 nm, is
      kinetically stabilized. The UV-visible absorbance spectrum of the reduced enzyme
      is typical of the anionic form of a flavin, with a peak centered at 335 nm. The
      affinity of the enzyme for sulfite is low (Kd value of 13.8 +/- 0.9 mM at pH 7.0
      and 25 degreesC); this result, along with the stabilization of the neutral flavin
      semiquinone, suggests the presence of a weak positive charge near the N(1)-C(2)=O
      of FAD. The reduction potential of the enzyme is -367 mV. Benzoate and
      phenylacetic acid are competitive inhibitors, with Kis values of 5.1 +/- 0.6 and
      13.1 +/- 2.3 mM, respectively. Binding of benzoate to nitroalkane oxidase results
      in spectral changes similar to those observed with d-amino acid oxidase. The
      absorbance spectrum of the flavin bound to nitroalkane oxidase is pH-dependent,
      with a pKa value of 8.4.

PMID- 9558356
TI  - Joint molecular modeling and spectroscopic studies of DNA complexes of a
      bis(arginyl) conjugate of a tricationic porphyrin designed to target the major
      groove.
AB  - To target selectively the major groove of double-stranded B DNA, we have designed
      and synthesized a bis(arginyl) conjugate of a tricationic porphyrin (BAP). Its
      binding energies with a series of double-stranded dodecanucleotides, having in
      common a central d(CpG)2 intercalation site were compared. The theoretical
      results indicated a significant energy preference favoring major groove over
      minor groove binding and a preferential binding to a sequence encompassing the
      palindrome GGCGCC encountered in the Primary Binding Site of the HIV-1
      retrovirus. Spectroscopic studies were carried out on the complexes of BAP with
      poly(dG-dC) and poly(dA-dT) and a series of oligonucleotide duplexes having
      either a GGCGCC, CCCGGG, or TACGTA sequence. The results of UV-visible and
      circular dichroism spectroscopies indicated that intercalation of the porphyrin
      takes place in poly(dG-dC) and all the oligonucleotides. Thermal denaturation
      studies showed that BAP increased significantly the melting temperature of the
      oligonucleotides having the GGCGCC sequence, whereas it produced only a
      negligible stabilization of sequences having CCCGGG or TACGTA in place of GGCGCC.
      This indicates a preferential binding of BAP to GGCGCC, fully consistent with the
      theoretical predictions. IR spectroscopy on d(GGCGCC)2 indicated that the guanine
      absorption bands, C6=O6 and N7-C8-H, were shifted by the binding of BAP,
      indicative of the interactions of the arginine arms in the major groove. Thus,
      the de novo designed compound BAP constitutes one of the very rare intercalators
      which, similar to the antitumor drugs mitoxantrone and ditercalinium, binds DNA
      in the major groove rather than in the minor groove.

PMID- 9558357
TI  - Sequence specific collective motions in a winged helix DNA binding domain
      detected by 15N relaxation NMR.
AB  - The recognition between transcription factors and their DNA binding sites is a
      highly dynamic process. During transcriptional regulation, transcription factors
      must bind to or dissociate from their cognate DNA binding sites. The winged helix
      DNA binding motif is one of many highly conserved DNA binding motifs identified
      in transcription factors. Backbone dynamics has been studied on the 15N- and 2H
      enriched winged helix family member Genesis. Our data show that the overall
      motions of the single domain Genesis are better described by more than two
      autocorrelation times (taum). Our data also demonstrate that Genesis shows
      structure specific conformation exchange characterized by Rex. Therefore, our
      results indicate that the structure of Genesis is highly dynamic and that
      secondary structure elements in Genesis have collective motions in the nanosecond
      to millisecond time scale. Since the winged helix DNA binding motif is highly
      conserved, this unique dynamic property observed in Genesis is also likely to be
      conserved in other winged helix family members and important in DNA binding.

PMID- 9558358
TI  - Inhibition of calmodulin-activated smooth-muscle myosin light-chain kinase by
      calmodulin-binding peptides and fluorescent (phosphodiesterase-activating)
      calmodulin derivatives.
AB  - Aspects of the biochemistry of calmodulin have been addressed that bear on its
      cell biological role as a mediator of Ca2+ regulation. Calmodulin-binding
      peptides derived from the amino acid sequence of smooth-muscle myosin light-chain
      kinase (MLCK) were characterized as inhibitors of calmodulin activation of MLCK
      catalyzed phosphorylation of the smooth-muscle regulatory light chain (MLC). MLCK
      activity was determined by measuring the rate of formation of one of the reaction
      products, ADP, in a coupled enzymatic assay by continuous fluorimetric monitoring
      of NADH removal in 100 microM CaCl2 at ionic strength 0.15 M, pH 7.0 and 21
      degreesC. The Km value of calmodulin was 3.5 nM, a value 16-35-fold greater than
      the Kd value of calmodulin for MLCK [Torok, K., and Trentham D. R. (1994)
      Biochemistry 33, 12807-12820]. The different Km and Kd values are most likely
      associated with the rate-limiting step in MLC phosphorylation being associated
      with product release from MLCK. The values of the inhibition constants, Ki, were
      the following: Ac-R-R-K-W-Q-K-T-G-H-A-V-R-A-I-G-R-L-CONH2 (Trp peptide), 8.6 (+/
      1. 4 sd) pM; Y4-analogue of Trp peptide (Tyr peptide), 7.3 (+/-0.1) nM; and A-R-R
      K-W-Q-K-T-G-H-A-V-R-A-I-G-R-L-S-S (RS20-like peptide), 0. 11-0.39 nM. The Ki
      values were consistent with kinetically determined Kd values of the peptides to
      calmodulin. Kinetic determination of Kd values required the use of a
      fluorescently labeled calmodulin, 2-chloro-(epsilon-amino-Lys75)-[6-(4-N, N
      diethylamino-phenyl)-1,3,5-triazin-4-yl]-calmodulin (TA-calmodulin).1 Since, as
      here, Lys75 is a convenient labeling site on calmodulin for the introduction of
      fluorescent probes, the biological activity of the Lys-modified calmodulins was
      evaluated. TA-calmodulin and calmodulin selectively modified by 1-N, N
      dimethylaminonaphthalene-5-sulfonyl chloride (dansyl-C1) at Lys75 (dansyl
      calmodulin) were characterized as activators of cyclic AMP phosphodiesterase
      (PDE) and inhibitors of MLCK. The Km value for dansyl-calmodulin was equal to
      that of calmodulin, and that of TA-calmodulin was 3.5-fold greater. TA-calmodulin
      and Lys75-labeled dansyl-calmodulin thus distinguish between PDE and MLCK being
      agonists to the former and antagonists to the latter.

PMID- 9558359
TI  - Inhibition of type I and type II phospholipase A2 by phosphatidyl-ethanolamine
      linked to polymeric carriers.
AB  - We have previously shown that cell surface proteoglycans protect the cell
      membrane from the action of extracellular phospholipase A2 (PLA2) enzymes [Dan,
      P., Nitzan, D. W., Dagan, A., Ginsburg, I., and Yedgar, S. (1996) FEBS Lett. 383,
      75-78]. Cell-impermeable PLA2 inhibitors (ExPLIs) were prepared by linking
      phosphatidylethanolamine (PE) to polymeric carriers, specifically,
      carboxymethylcellulose, heparin, or hyaluronic acid. The structure of these
      inhibitors enables the incorporation of their PE moiety into the membrane while
      the polymer remains at the membrane surface. In the present study, we show that
      the ExPLIs are effective inhibitors of the hydrolysis of different phospholipids
      in biological (Escherichia coli) and model (phospholipid vesicle) membranes, by
      diverse types of PLA2 enzymes, specifically human recombinant synovial fluid and
      C. atrox (type II), as well as Naja mocambique and porcine pancreatic (type I)
      PLA2. It is proposed that the external polymers of the ExPLIs, which are anchored
      to the membrane by the PE, mimic the naturally occurring cell surface
      proteoglycans and similarly protect membranes from the action of exogenous PLA2.

PMID- 9558360
TI  - Phosphorylation of the gamma subunit of the retinal photoreceptor cGMP
      phosphodiesterase by the cAMP-dependent protein kinase and its effect on the
      gamma subunit interaction with other proteins.
AB  - Cyclic GMP phosphodiesterase, a key enzyme in phototransduction, is composed of P
      alpha beta and two P gamma subunits. Interaction of P gamma with P alpha beta or
      with the alpha subunit (T alpha) of transducin is crucial for the regulation of
      cGMP phosphodiesterase in retinal photoreceptors. Here we have investigated
      phosphorylation of P gamma by cAMP-dependent protein kinase and its functional
      effect on the P gamma interaction with P alpha beta or T alpha in vitro. P gamma,
      but not P gamma complexed with T alpha (both GTP and GDP forms), is
      phosphorylated. Measurement of 32P radioactivity in phosphorylated P gamma,
      analysis of phosphorylated P gamma by laser mass spectrometry, identification of
      phosphoamino acid, and phosphorylation of mutant forms of P gamma indicate that
      only threonine 35 in P gamma is phosphorylated. Phosphorylation of P gamma
      mutants also reveals that the C and N terminals of P gamma which are required for
      the regulation of P alpha beta functions are not involved in the P gamma
      phosphorylation but that arginine 33, which is ADP-ribosylated by an endogenous
      ADP-ribosyltransferase, is required for the phosphorylation. Phosphorylated P
      gamma has a higher inhibitory activity for trypsin-activated cGMP
      phosphodiesterase than nonphosphorylated P gamma, indicating that the P gamma-P
      alpha beta interaction is affected by P gamma phosphorylation. Nonphosphorylated
      P gamma inhibits both the GTPase activity of T alpha and the binding of a
      hydrolysis-resistant GTP analogue to T alpha, while P gamma phosphorylation
      reduces these inhibitory activities. These observations suggest that a P gamma
      domain containing threonine 35 is involved in the P gamma-T alpha interaction,
      and P gamma phosphorylation regulates the P gamma-T alpha interaction. Our
      observation suggests that P gamma phosphorylation by cAMP-dependent protein
      kinase may function for the regulation of phototransduction in vertebrate rod
      photoreceptors.

PMID- 9558361
TI  - Chemical rescue of Klebsiella aerogenes urease variants lacking the carbamylated
      lysine nickel ligand.
AB  - Klebsiella aerogenes urease possesses a dinuclear metallocenter in which two
      nickel atoms are bridged by carbamylated Lys217. To assess whether carbamate
      specific chemistry is required for urease activity, site-directed mutagenesis and
      chemical rescue strategies were combined in efforts to place a carboxylate group
      at the location of this metal ligand. Urease variants with Lys217 replaced by
      Glu, Cys, and Ala (K217E, K217C/C319A, and K217A proteins) were purified, shown
      to be activated by incubation with small organic acids plus Ni(II), and
      structurally characterized. K217C/C319A urease possessed a second change in which
      Cys319 was replaced by Ala in order to facilitate efforts to chemically modify
      Cys217; however, this covalent modification approach did not produce active
      urease. Chemical rescue of the K217E, K217C/C319A, and K217A variants required 2,
      2, and 10 h, respectively, to reach maximal activity levels. The highest activity
      generated [224 micromol of urea degraded.min-1.(mg of protein)-1, for K217C/C319A
      urease incubated with 500 mM formic acid and 10 mM Ni at pH 6.5] corresponded to
      56% of that measured for in vitro activation of the wild-type apoprotein. While
      the K217E apoprotein showed minimal structural perturbations, the K217C/C319A
      apoprotein showed a disordering of some active site residues, and the K217A
      apoprotein revealed a repositioning of His219 to allow the formation of a
      hydrogen bond with Thr169, thus replacing the hydrogen bond between the amino
      group of Lys217 and Thr169 in the native enzyme. Importantly, these structures
      allow rationalization of the relative rates and yields of chemical rescue
      experiments. The crystal structures of chemically rescued K217A and K217C/C319A
      ureases revealed a return of the active site residues to their wild-type
      positions. In both cases, noncovalently bound formate was structurally equivalent
      to the Lys-carbamate as the bridging metallocenter ligand. We conclude that
      carbamate-specific chemistry is not required for urease catalysis.

PMID- 9558362
TI  - The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic
      leukemia.

PMID- 9558363
TI  - Detection of infectious simian immunodeficiency virus in B- and T-cell lymphomas
      of experimentally infected macaques.
AB  - An increasing frequency of malignant lymphomas occurs among patients infected by
      human immunodeficiency virus. Because of the close similarities to human
      malignancies, we used a nonhuman primate model to study the pathogenesis of
      simian immunodeficiency virus (SIV)-associated malignancies. Specifically, we
      investigated (1) the presence of the SIV genome in tumor cells, (2) the presence
      of coinfecting viruses, and (3) the presence of a rearrangement of the
      immunoglobulin and c-myc genes. We observed 5 cases of non-Hodgkin's lymphomas (4
      of B- and 1 of T-cell origin) among 14 SIV-infected cynomolgus monkeys. No c-myc
      translocation was observed in the tumors, whereas B-cell lymphomas were
      characterized either by a monoclonal (in 2 of 4) or by an oligoclonal (in 2 of 4)
      VDJ rearrangements of the immunoglobulin heavy chain gene. Molecular, biological,
      and immunological analyses did show the presence of infectious SIV in the tumor
      cells of 1 T-cell and 2 oligoclonal B-cell lymphomas. Neither Simian T
      lymphotropic nor Epstein-Barr viruses were detectable, whereas Simian herpes
      virus Macaca fascicularis-1 was detectable at a very low copy number in 3 of 4 B
      cell lymphomas; however, only 1 of these also harbored the SIV genome. These
      results support the possibility that SIV may be directly involved in the process
      of B or T lymphomagenesis occurring in simian acquired immunodeficiency syndrome.

PMID- 9558364
TI  - Differential deactivation of human dendritic cells by endotoxin desensitization:
      role of tumor necrosis factor-alpha and prostaglandin E2.
AB  - The endotoxin (lipopolysaccharide)-induced cytokine response is followed by a
      state of unresponsiveness to lipopolysaccharide (LPS) referred to as LPS
      tolerance or endotoxin desensitization. LPS tolerance, which can be
      experimentally induced in vitro and in vivo, is also known to occur in septic
      disease. Here, we evaluated whether dendritic cells (DC), the most potent antigen
      presenting cells, are also subject to this phenomenon. Single doses of LPS added
      at the initiation of DC culture inhibited in a dose-dependent fashion the
      production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10),
      and IL-12, but not the production of IL-8, in response to a second LPS challenge
      in day-5 DC. In addition, the LPS-induced expression of the CD83 maturation
      antigen was inhibited in these cells. Moreover, the endocytic activity of DC
      generated in the presence of LPS was dramatically reduced. DC desensitized with
      LPS were potent stimulators of T-cell proliferation but poor inducers of
      interferon-gamma (IFN-gamma) production in the allogeneic mixed leukocyte
      reaction. TNF-alpha and prostaglandin E2, two major products of LPS stimulation,
      could replace LPS for the induction of tolerance to LPS. Moreover, treatment of
      desensitized DC with TNF-alpha plus prostaglandin E2 fully restored CD83
      expression and partially restored IL-12 production as well as the IFN-gamma
      inducing activity of DC in the mixed leukocyte reaction. Our data show that human
      DC are highly susceptible to the induction of LPS tolerance, which seems to be a
      state of differential deactivation in which some functions are impaired whereas
      others are retained. Tolerization at the level of the professional antigen
      presenting cell by inflammatory mediators may play an important role in septic
      disease and in the origin of cancers associated with chronic inflammation.

PMID- 9558365
TI  - Characterization of CKbeta8 and CKbeta8-1: two alternatively spliced forms of
      human beta-chemokine, chemoattractants for neutrophils, monocytes, and
      lymphocytes, and potent agonists at CC chemokine receptor 1.
AB  - Two new members of human beta-chemokine cDNA were isolated based on structural
      and functional similarities to human leukotactin-1. One of these clones was
      identical to the previously isolated human beta-chemokine, CKbeta8, whereas the
      other is a splicing variant of CKbeta8, therefore named CKbeta8-1. CKbeta8 was
      short in 51 nucleotides (17 amino acids) compared with CKbeta8-1. The mature
      proteins of CKbeta8-1 and CKbeta8 consisted of 116 and 99 amino acids with
      calculated molecular weights of 12,500 and 10,950, respectively. Both CKbeta8-1
      and CKbeta8 were potent agonists at CCR1. These chemokines chemoattracted
      neutrophils, monocytes, and lymphocytes. They also significantly suppressed
      colony formation by human bone marrow, granulocyte-macrophage, erythroid, and
      multipotential progenitor cells stimulated by combinations of growth factors. To
      our knowledge, this is the first example that an alternative splicing produces
      two active beta-chemokines from a single gene.

PMID- 9558366
TI  - A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute
      myeloid leukemia.
AB  - Chromosomal abnormalities of band 8p11 are associated with a distinct subtype of
      acute myeloid leukemia with French-American-British M4/5 morphology and prominent
      erythrophagocytosis by the blast cells. This subtype is usually associated with
      the t(8;16)(p11;p13), a translocation that has recently been shown to result in a
      fusion between the MOZ and CBP genes. We have cloned the inv(8)(p11q13), an
      abnormality associated with the same leukemia phenotype, and found a novel fusion
      between MOZ and the nuclear receptor transcriptional coactivator TIF2/GRIP-1/NCoA
      2. This gene has not previously been implicated in the pathogenesis of leukemia
      or other malignancies. MOZ-TIF2 retains the histone acetyltransferase homology
      domains of both proteins and also the CBP binding domain of TIF2. We speculate
      that the apparently identical leukemia cell phenotype observed in cases with the
      t(8;16) and the inv(8) arises by recruitment of CBP by MOZ-TIF2, resulting in
      modulation of the transcriptional activity of target genes by a mechanism
      involving abnormal histone acetylation.

PMID- 9558368
TI  - Loss of imprinting in disease progression in chronic myelogenous leukemia.
AB  - The pathophysiologic role of the Philadelphia chromosome translocation in chronic
      myelogenous leukemia (CML) has been known for nearly 20 years. However, the most
      significant morbidity and mortality in CML are caused by progression to blast
      crisis, about which comparatively little is known at the molecular level. Genomic
      imprinting is a chromosomal modification leading to parental-origin-specific gene
      expression in somatic cells. Recently, we and others have described loss of
      imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to
      biallelic rather than monoallelic expression in a wide variety of solid tumors.
      We have now examined the imprinting status of IGF2 in samples from CML patients
      in stable phase, accelerated phase, and blast crisis. Five of six stable-phase
      patients showed normal imprinting, but LOI was found in all six cases of advanced
      disease (three accelerated phase, three blast crisis), which was statistically
      highly significant (P < .01). Thus, LOI represents a novel type of genetic
      alteration in CML that appears to be specifically associated with disease
      progression.

PMID- 9558367
TI  - Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of
      normal definitive hematopoiesis and directly generates dysplastic hematopoietic
      progenitors.
AB  - The t(8;21)-encoded AML1-ETO chimeric product is believed to be causally involved
      in up to 15% of acute myelogenous leukemias through an as yet unknown mechanism.
      To directly investigate the role of AML1-ETO in leukemogenesis, we used gene
      targeting to create an AML1-ETO "knock-in" allele that mimics the t(8;21).
      Unexpectedly, embryos heterozygous for AML1-ETO (AML1-ETO/+) died around E13.5
      from a complete absence of normal fetal liver-derived definitive hematopoiesis
      and lethal hemorrhages. This phenotype was similar to that seen following
      homozygous disruption of either AML1 or CBFbeta. However, in contrast to AML1- or
      CBFbeta-deficient embryos, fetal livers from AML1-ETO/+ embryos contained
      dysplastic multilineage hematopoietic progenitors that had an abnormally high
      self-renewal capacity in vitro. To further document the role of AML1-ETO in these
      growth abnormalities, we used retroviral transduction to express AML1-ETO in
      murine adult bone marrow-derived hematopoietic progenitors. AML1-ETO-expressing
      cells were again found to have an increased self-renewal capacity and could be
      readily established into immortalized cell lines in vitro. Taken together, these
      studies suggest that AML1-ETO not only neutralizes the normal biologic activity
      of AML1 but also directly induces aberrant hematopoietic cell proliferation.

PMID- 9558369
TI  - High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral
      blood progenitor cell transplantation.
AB  - Optimal numbers of CD34(+) cells to be reinfused in patients undergoing
      peripheral blood progenitor cell (PBPC) transplantation after high-dose
      chemotherapy are still unknown. Hematologic reconstitution of 168
      transplantations performed in patients with lymphoproliferative diseases was
      analyzed according to the number of CD34(+) cells reinfused. The number of days
      from PBPC reinfusion until neutrophil recovery (>1.0 x 10(9)/L) and unsustained
      platelet recovery (>50 x 10(9)/L) were analyzed in three groups defined by the
      number of CD34(+) cells reinfused: a low group with less than or equal to 2.5 x
      10(6) CD34(+) cells/kg, a high group with greater than 15 x 10(6) CD34(+)
      cells/kg, and an intermediate group to which the former two groups were compared.
      The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and
      platelet recovery (P < .0001). The 41 high-group patients experienced
      significantly shorter engraftment compared with the intermediate group with a
      median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil
      recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to
      180+) days for platelet recovery (P < .0001). These patients required
      significantly less platelet transfusions (P = .002). In a multivariate analysis,
      the amount of CD34(+) cells reinfused was the only variable showing significance
      for neutrophil and platelet recovery. High-group patients had a shorter hospital
      stay (P = .01) and tended to need fewer days of antibotic administration (P =
      .12). In conclusion, these results suggest that reinfusion of greater than 15 x
      10(6) CD34(+) cells/kg after high-dose chemotherapy for lymphoproliferative
      diseases further shortens hematopoietic reconstitution, reduces platelet
      requirements, and may improve patients' quality of life.

PMID- 9558370
TI  - BCR-ABL antisense oligodeoxynucleotide in vitro purging and autologous bone
      marrow transplantation for patients with chronic myelogenous leukemia in advanced
      phase.
AB  - BCR-ABL antisense oligodeoxynucleotides (ODN) have provided evidence of
      antileukemia effect when tested in vitro against Philadelphia-positive (Ph-pos)
      cells and in vivo when injected into leukemic mice. On the basis of the results
      obtained in vitro at diagnosis, eight patients with chronic myelogenous leukemia
      (CML) were selected and submitted to autologous bone marrow transplantation
      (ABMT) with bone marrow (BM) cells purged in vitro with junction-specific (J-sp)
      BCR-ABL antisense ODN at the time of transformation in accelerated phase or
      during second chronic phase. Mononuclear BM cells were treated in vitro for 24 or
      72 hours with 150 micro/mL of antisense ODN yielding a median recovery of 47.6%
      mononuclear cells, 48.8% CD34(+) cells, and 20.3% clonogenic cells. After a
      conditioning regimen including busulphan and etoposide, the reinfused treated
      cells allowed engraftment and hematologic reconstitution in all patients.
      Evaluation of the antileukemic effect by standard cytogenetic analysis and
      fluorescence in situ hybridization showed a complete karyotypic response in two
      cases and a minimal or no response in the other six. The patient autografted in
      second chronic phase died in blast crisis 7 months after ABMT; of the seven
      patients autografted in transformation, three developed blast crisis 21 to 39
      months after reinfusion, one died from unrelated BMT complications 30 months
      after ABMT, and three are in persistent second chronic phase 14 to 26 months
      after autograft. The low toxicity of the protocol and the hemopoietic
      reconstitution observed in all patients make this approach feasible; the marked
      karyotypic response observed in some patients and the duration of the second
      chronic phase show that ODN-mediated BM purging and autograft is a promising
      treatment for this high-risk group of CML.

PMID- 9558371
TI  - Inhibition of P-glycoprotein and recovery of drug sensitivity of human acute
      leukemic blast cells by multidrug resistance gene (mdr1) antisense
      oligonucleotides.
AB  - To overcome the problem of multidrug resistance, we investigated the
      effectiveness of phosphrothioate antisense oligonucleotides (MDR1-AS) in
      suppressing multidrug resistance gene (mdr1) expression in drug-resistant acute
      myelogenous leukemia (AML) blast cells and the K562 adriamycin-resistant cell
      line K562/ADM. The percentage of cells with the mdr1 gene product P-glycoprotein
      (P-gp) was decreased from 100% to 26% by 20 micromol/L MDR1-AS in the K562/ADM
      cells, and from 48.1% to 10.2% by 2.5 micromol/L MDR1-AS in the AML blast cells.
      Western blot analysis also showed a decrease in the amount of P-gp in the MDR1-AS
      treated K562/ADM cells. This effect was specific to MDR1-AS, and not observed
      with sense or random control oligonucleotides. The expression of mdr1 mRNA in
      K562/ADM and AML blast cells treated with MDR1-AS was decreased compared with the
      random control. Intracellular rhodamine retention and [3H]daunorubicin also
      increased after antisense treatment. Chemosensitivity to daunorubicin increased
      in MDR1-AS-treated blast cells up to 5.9-fold in the K562/ADM cells and 3.0- to
      6.4-fold in the AML blast cells. The expression of mdr1 mRNA derived from colony
      cells decreased in the MDR1-AS-treated groups. No inhibitory effect of the
      oligonucleotides on normal bone marrow progenitors was observed. These findings
      suggest that MDR1-AS is useful to overcome multidrug resistance in the treatment
      of leukemia.

PMID- 9558372
TI  - The P2X1 receptor, an adenosine triphosphate-gated cation channel, is expressed
      in human platelets but not in human blood leukocytes.
AB  - Extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP)
      activate multiple types of P2-nucleotide receptors expressed in platelets or
      leukocytes. Electrophysiological and biochemical studies have indicated
      expression of the P2X1 receptor, an ATP-gated cation channel, in human and rat
      platelets, rat basophilic leukemia (RBL) cells, and phorbol myristate acetate
      (PMA)-differentiated HL-60 myeloid cells. Although these findings suggest that
      P2X1 receptors are present in both blood leukocytes and blood platelets, the
      relative levels of P2X1 receptor expression and function in human blood
      leukocytes and platelets have not been directly characterized. On the basis of
      both immunoblot analysis and functional assays of P2X1 receptor-mediated ionic
      fluxes, we report that there is significant expression of P2X1 receptors in human
      platelets, but not in neutrophils, monocytes, or blood lymphocytes. Thus, unlike
      platelets and myeloid progenitor cell lines, fully differentiated human blood
      leukocytes do not express functionally significant numbers of P2X1 receptors,
      suggesting the downregulation of P2X1 receptor gene expression during the
      differentiation of phagocytic leukocytes. By contrast, P2X1 receptor expression
      is strongly maintained during megakaryocytic differentiation and platelet
      release. Immunoblot analysis indicated that the platelet P2X1 receptor migrates
      as an approximately 60-kD protein during SDS-electrophoresis under reducing or
      nonreducing conditions. Treatment of platelet membranes with endoglycosidase-F
      causes the P2X1 receptor band to migrate as a 46-kD protein, verifying the highly
      glycosylated nature of the mature receptor protein. Additional studies of
      nucleotide-induced changes in Ca2+ influx/mobilization demonstrated that the
      platelet P2X1 receptors are pharmacologically distinct from the well
      characterized ADP receptors of these cells. This finding suggests a unique role
      for these ATP-gated ion channels during hemostasis or thrombosis.

PMID- 9558373
TI  - Interleukin-3-induced activation of the JAK/STAT pathway is prolonged by
      proteasome inhibitors.
AB  - One facet of cytokine receptor signaling involves the activation of signal
      transducers and activators of transcription (STATs). STATs are rapidly activated
      via tyrosine phosphorylation by Janus kinase (JAK) family members and
      subsequently inactivated within a short period. We investigated the effect of
      proteasome inhibition on interleukin-3 (IL-3) activation of the JAK/STAT pathway
      following stimulation of Ba/F3 cells. Treatment of Ba/F3 cells with the
      proteasome inhibitor, N-acetyl-L-leucinyl-L-leucinyl-norleucinal (LLnL), led to
      stable tyrosine phosphorylation of the IL-3 receptor, beta common (betac), and
      STAT5 following stimulation. The effects of LLnL were not restricted to the
      JAK/STAT pathway, as Shc and mitogen-activated protein kinase (MAPK)
      phosphorylation were also prolonged in LLnL-treated cells. Further investigation
      showed these stable phosphorylation events were the result of prolonged
      activation of JAK2 and JAK1. These observations were confirmed using
      pharmacologic inhibitors. In the presence of LLnL, stable phosphorylation of
      STAT5 and betac was abrogated if the tyrosine kinase inhibitor, staurosporine,
      was added. The effect of staurosporine on STAT5 phosphorylation could be overcome
      if the phosphatase inhibitor, vanadate, was also added, suggesting phosphorylated
      STAT5 could be stabilized by phosphatase, but not by proteasome inhibition per
      se. These observations are consistent with the hypothesis that proteasome
      mediated protein degradation can modulate the activity of the JAK/STAT pathway by
      regulating the deactivation of JAK.

PMID- 9558374
TI  - Regulation of the erythroid transcription factor NF-E2 by cyclic adenosine
      monophosphate-dependent protein kinase.
AB  - Activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (A
      kinase) promotes hemoglobin synthesis in several erythropoietin-dependent cell
      lines, whereas A-kinase-deficient murine erythroleukemia (MEL) cells show
      impaired hemoglobin production; A-kinase may regulate the erythroid transcription
      factor NF-E2 by directly phosphorylating its p45 subunit or by changing p45
      interactions with other proteins. We have mapped the major A-kinase
      phosphorylation site of p45 to Ser(169); Ala substitution for Ser(169) resulted
      in a protein that was no longer phosphorylated by A-kinase in vitro or in vivo.
      The mutant protein formed NF-E2 complexes that bound to DNA with the same
      affinity as wild-type p45 and functioned normally to restore beta-globin gene
      expression in a p45-deficient MEL cell line. Transactivation properties of the
      (Ser (169)--> Ala) mutant p45 were also indistinguishable from wild-type p45 when
      Gal4-p45 fusion constructs were tested with a Gal4-dependent reporter gene.
      Transactivation of the reporter by both mutant and wild-type p45 was
      significantly enhanced when A-kinase was activated by membrane-permeable cAMP
      analogs or when cells were cotransfected with the catalytic subunit of A-kinase.
      Stimulation of p45 transactivation by A-kinase required only the N-terminal
      transactivation domain of p45, suggesting that A-kinase regulates the interaction
      of p45 with downstream effectors.

PMID- 9558375
TI  - Generation of a primitive erythroid cell line and promotion of its growth by
      basic fibroblast growth factor.
AB  - An immortalized cell line representing the primitive erythroid (EryP) lineage was
      established from in vitro-differentiated progeny (embryoid bodies [EBs]) of
      embryonic stem (ES) cells using a retroviral insertional mutation, and has been
      termed EB-PE for embryoid body-derived primitive erythroid. Even though EB-PE
      cells are immortalized, they show characteristics of normal EryP cells, such as
      gene expression and growth factor dependency. In addition, EB-PE cells can
      differentiate further in culture. Investigation of growth factor requirements of
      EB-PE cells showed that basic fibroblast growth factor (bFGF) and erythropoietin
      (Epo) play unique roles in EB-PE proliferation and differentiation. While bFGF
      was a strong mitogen, Epo was required for both proliferation and
      differentiation. The unique proliferative response to bFGF coincided with
      upregulation of its receptor, fibroblast growth factor receptor (fgfr-1), and
      downregulation of erythropoietin receptor (EpoR) gene expression. Studies of
      primary EryP cells derived from early EBs, when tested in a colony-formation
      assay, also provided evidence for the mitogenic role of bFGF in concert with Epo.

PMID- 9558376
TI  - Systematic method to obtain novel genes that are regulated by mi transcription
      factor: impaired expression of granzyme B and tryptophan hydroxylase in mi/mi
      cultured mast cells.
AB  - The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper
      protein family of transcription factors (hereafter called MITF). We have reported
      that the expression of several genes was impaired in cultured mast cells (CMCs)
      of mi/mi genotype, and demonstrated the involvement of MITF in the transcription
      of these genes. To obtain new genes whose transcription may be regulated by MITF,
      we prepared a subtracted cDNA library using +/+ and mi/mi CMCs. We found two
      clones carrying the granzyme (Gr) B and tryptophan hydroxylase (TPH) cDNAs in the
      subtracted library. The expression of the Gr B and TPH genes decreased in mi/mi
      CMCs, and recovered to nearly normal level by the overexpression of normal (+)
      MITF but not of mutant (mi) MITF. The +-MITF bound three and one CANNTG motifs in
      the Gr B and TPH promoters, respectively, and transactivated these two genes,
      indicating the involvement of +-MITF in their expression. Because TPH is the rate
      limiting enzyme for serotonin synthesis, we examined the serotonin content of +/+
      and mi/mi CMCs. The serotonin content was significantly smaller in mi/mi CMCs
      than in +/+ CMCs. The introduction of +-MITF but not of mi-MITF normalized the
      serotonin content in mi/mi CMCs.

PMID- 9558377
TI  - Interactions of erythropoietin, granulocyte colony-stimulating factor, stem cell
      factor, and interleukin-11 on murine hematopoiesis during simultaneous
      administration.
AB  - We investigated how in vivo effects of single hematopoietic cytokines change if
      given in combination for a prolonged time. Mice were treated with every
      combination of recombinant human (rh) erythropoietin (EPO), rh granulocyte colony
      stimulating factor (G-CSF), recombinant rat (rr) stem cell factor (SCF), and rh
      interleukin (IL)-11 by continuous infusion over 7 days (full factorial design
      with three dose levels for each cytokine). Burst-forming unit-erythroid (BFU-E),
      colony-forming unit-erythroid (CFU-E), and colony-forming unit-granulocyte
      macrophage (CFU-GM) were determined in bone marrow and spleen, reticulocytes,
      hematocrit, granulocytes, and thrombocytes in the peripheral blood. An analysis
      of variance (ANOVA) and multiple comparison of means was used to evaluate the
      data. For several cell types, cytokine effects superimposed in an additive way if
      combined. However, in a large number of circumstances, nonadditive pairwise
      interactions were found. They differed in type and magnitude involving high-dose
      saturation, high-dose antagonistic effects, and even effect reversals
      (qualitative interactions). Hence, in general, it was not possible to foresee the
      combination effects on the basis of existing knowledge of single effects. On the
      other hand, the cytokine network was robust and no system hazards were observed
      under multiple cytokine combinations. The results illustrate that the cytokine
      network has nonlinear dynamic properties in vivo with dose-response
      characteristics of one cytokine being continuously modified by other cytokines.

PMID- 9558378
TI  - The effect of alpha4 beta1-integrin binding sequences of fibronectin on growth of
      cells from human hematopoietic progenitors.
AB  - Highly regulated interactions between adhesion receptors on progenitor cells and
      their extracellular matrix ligands are essential for the control of hematopoiesis
      in bone marrow stroma. We have examined the relationship between alpha4beta1
      integrin-mediated adhesion and growth of CD34(+) cells by assessing their
      adhesive and migratory patterns of proliferation in a mixture of hematopoietic
      growth factors in the presence of different recombinant fragments of the
      HepII/IIICS region of fibronectin. CD34(+) cells were isolated from cord blood
      and placed in culture wells containing serum-free medium and growth factors.
      Wells were precoated with either the H120 fragment of fibronectin, which contains
      three alpha4beta1-integrin binding sites, or the H0 fragment, which lacks the two
      highest affinity alpha4beta1 binding sequences. Proliferation of single cells of
      CD34(+)38(+)DR+ and CD34(+)38(-)DR+ phenotypes occurred in contact with the H120
      substrate and was associated with migration. Larger numbers of cells were used to
      quantitate proliferative responses. Cells growing in wells coated with H120
      formed attachments to the base of the wells throughout the culture period. Higher
      total cell counts were consistently found in wells coated with H120 compared with
      H0 and bovine serum albumin controls. The difference was first apparent at day 8
      of culture and reached a maximum at days 11 through 13, when expansion with H120
      was a mean of 1.8-fold higher than that seen with H0 (P</= .0001). The greatest
      expansion (2.25-fold) with H120 compared with H0 was seen when the growth factor
      concentrations were reduced to 1/16 of the standard levels (P </= .001). The
      increase in total cell numbers was not at the expense of CD34(+) cells as numbers
      of these were similar in H120 and control cultures. These results provide
      evidence for synergy between growth factors and integrins that may be relevant to
      understanding hematopoiesis in marrow stroma.

PMID- 9558379
TI  - Ineffective platelet production in thrombocytopenic human immunodeficiency virus
      infected patients.
AB  - Thrombocytopenia has been characterized in six patients infected with human
      immunodeficiency virus (HIV) with respect to the delivery of viable platelets
      into the peripheral circulation (peripheral platelet mass turnover), marrow
      megakaryocyte mass (product of megakaryocyte number and volume), megakaryocyte
      progenitor cells, circulating levels of endogenous thrombopoietin (TPO) and
      platelet TPO receptor number, and serum antiplatelet glycoprotein (GP) IIIa49-66
      antibody (GPIIIa49-66Ab), an antibody associated with thrombocytopenia in HIV
      infected patients. Peripheral platelet counts in these patients averaged 46 +/-
      43 x 10(3)/microL (P = . 0001 compared to normal controls of 250 +/- 40x
      10(3)/microL), and the mean platelet volume (MPV) was 10.5 +/- 2.0 fL (P > 0.3
      compared with normal control of 9.5 +/- 1.7 fL). The mean life span of autologous
      111In-platelets was 87 +/- 39 hours (P = .0001 compared with 232 +/- 38 hours in
      20 normal controls), and immediate mean recovery of 111In-platelets injected into
      the systemic circulation was 33% +/- 16% (P = .0001 compared with 65% +/- 5% in
      20 normal controls). The resultant mean peripheral platelet mass turnover was 3.8
      +/- 1.5 x 10(5) fL/microL/d versus 3.8 +/- 0.4 x 10(5) fL/microL/d in 20 normal
      controls (P > .5). The mean endogenous TPO level was 596 +/- 471 pg/mL (P = .0001
      compared with 95 +/- 6 pg/mL in 98 normal control subjects), and mean platelet
      TPO receptor number was 461 +/- 259 receptors/platelet (P = .05 compared with 207
      +/- 99 receptors/platelet in nine normal controls). Antiplatelet GPIIIa49-66Ab
      levels in sera were uniformly increased in HIV thrombocytopenic patients (P <
      .001). In this cohort of thrombocytopenic HIV patients, marrow megakaryocyte
      number was increased to 30 +/- 15 x 10(6)/kg (P = .02 compared with 11 +/- 2.1 x
      10(6)/kg in 20 normal controls), and marrow megakaryocyte volume was 32 +/- 0.9 x
      10(3) fL (P = .05 compared with 28 +/- 4.5 x 10(3) fL in normal controls). Marrow
      megakaryocyte mass was expanded to 93 +/- 47 x 10(10) fL/kg (P = .007 compared
      with normal control of 31 +/- 5.3 x 10(10) fL/kg). Marrow megakaryocyte
      progenitor cells averaged 3.3 (range, 0.4 to 7.3) CFU-Meg/1,000 CD34(+) cells
      compared with 27 (range, 0.1 to 84) CFU-Meg/1,000 CD34(+) cells in seven normal
      subjects (P = .02). Thus, thrombocytopenia in these HIV patients was caused by a
      combination of shortening of platelet life span by two thirds and doubling of
      splenic platelet sequestration, coupled with ineffective delivery of viable
      platelets to the peripheral blood, despite a threefold TPO-driven expansion in
      marrow megakaryocyte mass. We postulate that this disparity between circulating
      platelet product and marrow platelet substrate results from direct impairment in
      platelet formation by HIV-infected marrow megakaryocytes.

PMID- 9558380
TI  - Identification of human and mouse hematopoietic stem cell populations expressing
      high levels of mRNA encoding retrovirus receptors.
AB  - One obstacle to retrovirus-mediated gene therapy for human hematopoietic
      disorders is the low efficiency of gene transfer into pluripotent hematopoietic
      stem cells (HSC). We have previously shown a direct correlation between
      retrovirus receptor mRNA levels in mouse HSC and the efficiency with which they
      are transduced. In the present study, we assayed retrovirus receptor mRNA levels
      in a variety of mouse and human HSC populations to identify HSC which may be more
      competent for retrovirus transduction. The highest levels of amphotropic
      retrovirus receptor (amphoR) mRNA were found in cryopreserved human cord blood
      HSC. The level of amphoR mRNA in Lin- CD34(+) CD38(-) cells isolated from frozen
      cord blood was 12-fold higher than the level in fresh cord blood Lin- CD34(+)
      CD38(-) cells. In mice, the level of amphoR mRNA in HSC from the bone marrow (BM)
      of mice treated with stem cell factor and granulocyte-colony stimulating factor
      was 2.8- to 7.8-fold higher than in HSC from the BM of untreated mice. These
      findings suggest that HSC from frozen cord blood and cytokine-mobilized BM may be
      superior targets for amphotropic retrovirus transduction compared with HSC from
      untreated adult BM.

PMID- 9558381
TI  - Telomerase activity in candidate stem cells from fetal liver and adult bone
      marrow.
AB  - Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric repeats
      onto the 3' ends of eukaryotic chromosomes. Activation of telomerase may prevent
      telomeric shortening and correlates with cell immortality in the germline and
      certain tumor cells. Candidate hematopoietic stem cells (HSC) from adult bone
      marrow express low levels of telomerase, which is upregulated with proliferation
      and/or differentiation. To address this issue, we stimulated purified candidate
      HSC from human adult bone marrow with stem cell factor (SCF), interleukin-3 (IL
      3), and Flt3-ligand (FL). After 5 days in culture, activity was detected in total
      cell extracts from IL-3-, SCF + FL-, SCF + IL-3-, FL + IL-3-, and SCF + IL-3 + FL
      stimulated cultures, but not from cells cultured in SCF or FL alone. Within the
      CD34(+) fraction of the cultured cells, significant activity was found in the
      CD34(+)CD71(+) fraction. In addition, PKH26 staining confirmed that detectable
      telomerase activity was present in dividing PKH26(lo) cells, whereas nondividing
      PKH26(hi) cells were telomerase negative. Because in these experiments no
      distinction could be made between cycling "candidate" stem cells that had
      retained or had lost self-renewal properties, fetal liver cells with a
      CD34(+)CD38(-) phenotype, highly enriched for cycling stem cells, were also
      examined and found to express readily detectable levels of telomerase activity.
      Given the replication-dependent loss of telomeric DNA in hematopoietic cells,
      these observations suggest that the observed telomerase activity in candidate
      stem cells is either expressed in a minor subset of stem cells or, more likely,
      is not sufficient to prevent telomere shortening.

PMID- 9558382
TI  - Growth-supporting activities of fibronectin on hematopoietic stem/progenitor
      cells in vitro and in vivo: structural requirement for fibronectin activities of
      CS1 and cell-binding domains.
AB  - Fibronectin (FN) is supposed to play important roles in various aspects of
      hematopoiesis through binding to very late antigen 4 (VLA4) and VLA5. However,
      effects of FN on hematopoietic stem cells are largely unknown. In an effort to
      determine if FN had a growth-supporting activity on hematopoietic stem cells,
      human CD34(+)/VLA4(bright)/VLA5(dull) hematopoietic stem cells and a murine stem
      cell factor (SCF)-dependent multipotent cell line, EML-C1, were treated with or
      without FN in a serum and growth-factor-deprived medium, and then subjected to
      clonogenic assay in the presence of hematopoietic growth factors. The
      pretreatment of the CD34(+) cells with FN gave rise to significantly increased
      numbers of granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst
      colony-forming units, and mixed erythroid-myeloid colony-forming units. In
      addition, the numbers of blast colony-forming units and CFU-GM that developed
      after culture of EML-C1 cells with SCF and the combination of SCF and interleukin
      3, respectively, were augmented by the pretreatment with FN. The augmented colony
      formation by FN was completely abrogated by the addition of CS1 fragment, but not
      of GRGDSP peptide, suggesting an essential role of FN-VLA4 interaction in the FN
      effects. Furthermore, the effects of various FN fragments consisting of RGDS
      containing cell-binding domain (CBD), heparin-binding domain (HBD), and/or CS1
      portion were tested on clonogenic growth of CD34(+) cells. Increased colony
      formation was induced by CBD-CS1 and CBD-HBD-CS1 fragments, but not with other
      fragments lacking CBD or CS1 domains, suggesting that both CS1 and CBD of FN were
      required for the augmentation of clonogenic growth of hematopoietic
      stem/progenitor cells in vitro. In addition to the in vitro effects, the in vivo
      administration of CBD-CS1 fragment into mice was found to increase the numbers of
      hematopoietic progenitor cells in bone marrow and spleen in a dose-dependent
      manner. Thus, FN may function on hematopoietic stem/progenitor cells as a growth
      supporting factor in vitro and in vivo.

PMID- 9558383
TI  - Sustained phenotypic correction of murine hemophilia A by in vivo gene therapy.
AB  - Hemophilia A is caused by a deficiency of blood coagulation factor VIII (FVIII)
      and has been widely discussed as a candidate for gene therapy. While the natural
      canine model of hemophilia A has been valuable for the development of FVIII
      pharmaceutical products, the use of hemophiliac dogs for gene therapy studies has
      several limitations such as expense and the long canine generation time. The
      recent creation of two strains of FVIII-deficient mice provides the first small
      animal model of hemophilia A. Treatment of hemophiliac mice of both genotypes
      with potent, human FVIII-encoding adenoviral vectors resulted in expression of
      biologically active human FVIII at levels, which declined, but remained above the
      human therapeutic range for over 9 months. The duration of expression and FVIII
      plasma levels achieved were similar in both hemophiliac mouse strains. Treated
      mice readily survived tail clipping with minimal blood loss, thus showing
      phenotypic correction of murine hemophilia A by in vivo gene therapy.

PMID- 9558385
TI  - Platelet factor 4 modulates fibroblast growth factor 2 (FGF-2) activity and
      inhibits FGF-2 dimerization.
AB  - Platelet factor 4 (PF-4) inhibits angiogenesis in vitro and in vivo. The
      mechanism of inhibition is poorly understood. We have investigated the mechanism
      of inhibition by examining the interaction of PF-4 and the fibroblast growth
      factor-2 (FGF-2)/fibroblast growth factor receptor (FGFR) system. PF-4 inhibited
      the binding of FGF-2 to high-affinity and low-affinity binding sites in murine
      microvascular endothelial cells (LEII cells) and proliferation. Maximum
      inhibition of binding to endothelial FGF receptors was observed at PF-4
      concentrations between 5 and 10 microg/mL (half maximum inhibition at 0.6
      micro/mL), and proliferation was completely inhibited at 2 microg/mL. At this
      concentration, PF-4 reduced internalization of 125I-FGF-2 by threefold and
      delayed degradation. To gain insight into the mechanism of inhibition, we have
      analyzed the interaction of PF-4 with FGF-2/FGFR by using mutant heparan sulfate
      deficient Chinese hamster ovary (CHO) cells transfected with the FGFR-1 cDNA
      (CHOm-FGFR-1) and by examining the direct interaction with FGF-2. In the absence
      of heparin, PF-4 inhibited binding of 125I-FGF-2 to CHOm-FGFR-1 cells in a
      concentration-dependent manner, although not completely. In the presence of
      heparin, PF-4 abolished totally the stimulatory effect of heparin. Furthermore,
      PF-4 complexed to FGF-2 and inhibited endogenous or heparin-induced FGF-2
      dimerization. These results indicate that PF-4 interacts with FGF-2 by complex
      formation, inhibiting FGF-2 dimerization, binding to FGF receptors, and
      internalization. This mechanism most likely contributes to the antiangiogenic
      properties of PF-4.

PMID- 9558384
TI  - Factor XIIIa cross-linking of the Marburg fibrin: formation of alpham.gamman
      heteromultimers and the alpha-chain-linked albumin. gamma complex, and disturbed
      protofibril assembly resulting in acquisition of plasmin resistance relevant to
      thrombophila.
AB  - The truncated Aalpha-chain of fibrinogen Marburg is partly linked with albumin by
      a disulfide bond. Based on the recovery of the first six amino acid residues
      assigned to the subunit polypeptides of fibrinogen (the Aalpha-and gamma-chains)
      and albumin, 0.33 mol of albumin was estimated to be linked to 1 mol of the
      Marburg fibrinogen. When the Marburg fibrinogen was clotted with thrombin-factor
      XIIIa-Ca2+, various alpham gamman heteromultimers were produced, and part of the
      albumin was cross-linked to the gamma-chain. Acid-solubilized Marburg fibrin
      monomer failed to form large aggregates that could be detected by monitoring
      turbidity at A350, but it was able to enhance tissue-type plasminogen-activator
      catalyzed plasmin generation, though not as avidly as the normal control,
      indicating that the double-stranded protofibrils had, to some extent, been
      constructed. This idea seems to be supported by normal factor XIIIa-catalyzed
      cross-linking of the fibrin gamma-chains. However, the cross-linked Marburg
      fibrin, being apparently fragile and translucent, was highly resistant against
      plasmin, and its subunit components were considerably retained for 48 hours as
      noted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Although the
      exact mechanisms are still unclear, the albumin-incorporated factor XIIIa-cross
      linked Marburg fibrin seems to have undergone a critical structural alteration(s)
      to acquire resistance against plasmin. This aquisition of plasmin resistance may
      be contributed to the postoperative pelvic vein thrombosis and recurrent
      pulmonary embolisms in the patient after caesarian section for her first delivery
      at the age of 20 years.

PMID- 9558386
TI  - Hypoxia stimulates urokinase receptor expression through a heme protein-dependent
      pathway.
AB  - Hypoxia underlies a number of biologic processes in which cellular migration and
      invasion occur. Because earlier studies have shown that the receptor for
      urokinase-type plasminogen activator (uPAR) may facilitate such events, we
      studied the effect of hypoxia on the expression of uPAR by first trimester human
      trophoblasts (HTR-8/SVneo) and human umbilical vein endothelial cells (HUVEC).
      Compared with control cells cultured under standard conditions (20% O2), HTR
      8/SVneo cells and HUVEC cultured in 1% O2 expressed more uPAR, as determined by
      flow cytometric and [125I]-prourokinase ligand binding analyses. Increased uPAR
      expression paralleled increases in uPAR mRNA. The involvement of a heme protein
      in the hypoxia-induced expression of uPAR was suggested by the observations that
      culture of cells with cobalt chloride, or sodium 4, 5-dihydroxybenzene-1,3
      disulfonate (Tiron), an iron-chelating agent, also stimulated uPAR expression,
      and that the hypoxia-induced uPAR expression was inhibited by adding carbon
      monoxide to the hypoxic atmosphere. Culture of HTR-8/SVneo cells with vascular
      endothelial growth factor (VEGF) did not increase uPAR mRNA levels, suggesting
      that the hypoxia-mediated effect on uPAR expression by these cells did not occur
      through a VEGF-dependent mechanism. The functional importance of these findings
      is suggested by the fact that HTR-8/SVneo cells cultured under hypoxia displayed
      higher levels of cell surface plasminogen activator activity and greater invasion
      through a reconstituted basement membrane. These results suggest that hypoxia may
      promote cellular invasion by stimulating the expression of uPAR through a heme
      protein-dependent pathway.

PMID- 9558387
TI  - gp130, the cytokine common signal-transducer of interleukin-6 cytokine family, is
      downregulated in T cells in vivo by interleukin-6.
AB  - gp130 is a common signal-transducing receptor component for the interleukin-6 (IL
      6) family of cytokines. To investigate the expression of gp130 in T-cell subsets
      and its regulation, anti-murine gp130 monoclonal antibody (MoAb) was used for
      flow cytometric analysis. In normal mice, gp130 was differentially expressed in
      thymocyte and splenic T-cell subpopulations defined by CD4/CD8 expression. In
      aged MRL/lpr mice, although gp130 expression was detectable in splenic CD4(+) or
      CD8(+) T cells, gp130 expression was significantly downregulated. Because serum
      levels of IL-6 and soluble IL-6 receptor (sIL-6R) are elevated in these mice, we
      examined the possibility that the downregulation of gp130 expression on splenic T
      cells might be produced in response to continuous activation of gp130 by high
      levels of serum IL-6. In transgenic mice overexpressing IL-6, gp130 expression in
      the splenic T cells was significantly decreased. After stimulation with IL-6 in
      vitro, the level of gp130 on CD4(+) or CD8(+) splenic T cells from normal mice
      was significantly decreased. These results suggest that the expression of gp130
      in splenic T cells could be downregulated by the IL-6 stimulation under
      physiological or pathological circumstances.

PMID- 9558388
TI  - Interleukin-12 inhibits graft-versus-host disease through an Fas-mediated
      mechanism associated with alterations in donor T-cell activation and expansion.
AB  - We have recently made the paradoxical observation that a single injection of
      recombinant murine interleukin-12 (IL-12) on the day of bone marrow
      transplantation (BMT) inhibits graft-versus-host disease (GVHD) in lethally
      irradiated mice receiving fully major histocompatability complex (MHC)-mismatched
      bone marrow and spleen cells. We have now examined the mechanism of this effect
      of IL-12 on acute GVHD. By day 4 post-BMT, IL-12-treated mice showed marked
      reductions in splenic donor CD4(+) and CD8(+) T cells compared with GVHD
      controls. Expression of the early activation markers IL-2R alpha chain (CD25) and
      CD69 on splenic donor CD4(+) cells was considerably higher at early time points
      (36 and 72 hours post-BMT) in IL-12-treated mice compared with GVHD controls.
      However, the later, GVHD-associated increase in CD25 and very late antigen-4 (VLA
      4) expression on donor T cells was greatly depressed in IL-12-protected mice
      compared with GVHD controls. The marked GVHD-associated expansion of host
      reactive T helper cells by day 4 was also completely inhibited in the IL-12
      treated group. Expression of Fas was increased on donor CD4 cells of IL-12
      treated mice compared with those of controls on days 3 through 7 post-BMT.
      Furthermore, the ability of IL-12 to protect against GVHD was at least partially
      dependent on the ability of donor cells to express functional Fas molecules. We
      conclude that IL-12 treatment at the time of BMT markedly perturbs the activation
      of alloreactive donor CD4(+) T cells that play a critical role in the
      pathogenesis of acute GVHD. We hypothesize that these perturbations culminate in
      Fas-dependent apoptosis of donor T cells, thus impeding their expansion and their
      GVHD-promoting activity.

PMID- 9558389
TI  - High CD30 ligand expression by epithelial cells and Hassal's corpuscles in the
      medulla of human thymus.
AB  - CD30 is a member of tumor necrosis factor (TNF) receptor superfamily that is
      expressed by activated T cells in the presence of interleukin-4 (IL-4). Although
      CD30 can mediate a variety of signals, CD30-deficient mice have impaired negative
      selection of T cells, suggesting that at least in the context of murine thymus,
      CD30 is a cell death-mediating molecule. The ligand for CD30 (CD30L) is a
      membrane-associated glycoprotein related to TNF, which is known to be expressed
      mainly by activated T cells and other leukocytes. However, the nature of CD30L
      expressing cells involved in the interaction with CD30+ thymocytes is unclear. We
      report here that in postnatal human thymus the great majority of CD30+ cells are
      double positive (CD4+CD8+), activated, IL-4 receptor-expressing T cells which
      selectively localize in the medullary areas. Moreover, many medullary epithelial
      cells and Hassal's corpuscles in the same thymus specimens showed unusually high
      expression of CD30L in comparison with other lymphoid or nonlymphoid tissues.
      These findings provide additional information on the nature and localization of
      CD30+ thymocytes and show that epithelial cells are the major holder of CD30L in
      the thymic medulla.

PMID- 9558390
TI  - Myc is essential for transformation by TEL/platelet-derived growth factor
      receptor beta (PDGFRbeta).
AB  - The t(5;12) translocation identified in patients with chronic myelomonocytic
      leukemia (CMML) encodes a TEL/platelet-derived growth factor receptor beta
      (PDGFRbeta) fusion protein. A key hypothesis for how the TEL/PDGFRbeta fusion
      protein would function as an oncogene is that it represents a constitutively
      active version of the normal PDGFRbeta. A link between the function of the
      t(5;12)-encoded TEL/PDGFRbeta fusion protein and Myc expression is suggested by
      the fact that Myc is induced by PDGF and is essential for entry of cells into the
      S phase of the cell cycle. We here show that the kinase activity of TEL/PDGFRbeta
      is necessary for Ba/F3 cells to acquire interleukin-3 (IL-3) independence and
      that, in contrast to their untransfected counterpart, Ba/F3 cells stably
      transfected with TEL/PDGFRbeta maintain a high level of Myc expression after
      removal of IL-3. Using dominant negative mutants of Myc, we show that a threshold
      of active Myc is essential for TEL/PDGFRbeta to transform Ba/F3 and Rat-1 cells.
      The findings that the kinase activity of TEL/PDGFRbeta and a threshold of active
      Myc are involved in TEL/PDGFRbeta transformation may allow for the development of
      therapeutic strategies in patients with t(5;12)+ CMML using specific inhibitors
      of the PDGFRbeta kinase as well as compounds designed to interfere specifically
      with Myc.

PMID- 9558391
TI  - Detection of lymphoma in bone marrow by whole-body positron emission tomography.
AB  - Positron emission tomography (PET) is a whole-body imaging technique using 18
      fluorine-fluorodeoxyglucose (FDG), whose uptake is increased in tumor cells.
      Published studies have shown PET to be an effective method of staging lymphoma
      and to be more sensitive than CT at detecting extranodal disease. The purpose of
      this study was to determine whether the increased marrow uptake of FDG observed
      in some lymphoma patients during routine staging PET scans represented marrow
      involvement by disease. PET scans of 50 patients with Hodgkin's (12) and non
      Hodgkin's (38) lymphoma were analyzed by three independent observers and the
      marrow graded as normal or abnormal using a visual grading system. Unilateral
      iliac crest marrow aspirates and biopsies were performed on all patients. The PET
      scan and marrow histology agreed in 39 patients (78%), being concordant positive
      in 13 and concordant negative in 26 patients. In 8 patients the PET scan showed
      increased FDG uptake but staging biopsy was negative; in 4 of these 8 patients
      the PET scan showed a normal marrow background with focal FDG "hot spots" distant
      from the site biopsied. In 3 patients the marrow biopsy specimen was positive but
      the PET scan normal; 2 of these 3 patients had non-Hodgkin's lymphoma whose
      malignant cells did not take up FDG at lymph node or marrow disease sites.
      Therefore, there were only 5 patients (10%) in whom there was a difference
      between the PET scan and biopsy result which could not be fully explained. Visual
      interpretation of marrow FDG uptake during whole-body staging PET scans can
      correctly assess marrow disease status in a high proportion of lymphoma patients.
      PET has the potential to reduce the need for staging marrow biopsy.

PMID- 9558392
TI  - Constitutive expression of the promyelocytic leukemia-associated oncogene PML
      RARalpha in TF1 cells: isoform-specific and retinoic acid-dependent effects on
      growth, bcl-2 expression, and apoptosis.
AB  - Two major isoforms of PML-RARalpha are associated with (15;17)-positive acute
      promyelocytic leukemia (APL); however, functional differences between these
      isoforms have been difficult to define, and the molecular mechanism by which each
      isoform contributes to the pathogenesis of APL is not fully understood. To
      address these issues, the 'short' (S) and 'long' (L) isoforms of PML-RARalpha
      were constitutively expressed in the factor-dependent human erythroleukemia cell
      line, TF1. Expression of the L, but not the S, isoform inhibited growth of these
      cells in the presence of granulocyte-macrophage colony-stimulating factor (GM
      CSF). In the absence of GM-CSF, the S isoform partially protected against
      apoptosis, while the L isoform accelerated cell death. Treatment with all-trans
      retinoic acid (ATRA) inhibited cell growth and caused apoptosis only in PML
      RARalpha-expressing cells, and these effects of ATRA were more marked in cells
      expressing the L isoform. ATRA treatment also led to downregulation of bcl-2 and
      endogenous RARalpha in PML-RARalpha-expressing cells, but had little effect on
      the level of exogenously expressed PML-RARalpha. We conclude that (1) subtle
      differences exist in the biologic activities of the L and S isoforms of PML
      RARalpha, and (2) both isoforms are capable of transducing an ATRA-mediated
      signal that leads to downregulation of bcl-2 and induction of programmed cell
      death.

PMID- 9558393
TI  - Highly sensitive fluorescence in situ hybridization method to detect double
      BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia.
AB  - We investigated a new method using fluorescence in situ hybridization and DNA
      probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect
      double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one
      on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph
      chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic,
      simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30
      normal specimens, the mean percentage of false-positive cells was 0.25 +/- 0.39.
      Thirty-seven specimens from 10 patients were studied before treatment and two or
      more times at 4-month intervals after treatment with interferon-alpha2b (IFN
      alpha2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in
      these specimens correlated closely with quantitative cytogenetics and accurately
      quantified disease within a few percent. We studied 6, 000 nuclei for each of six
      specimens, three normal and three from patients with chronic myeloid leukemia
      (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and
      patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to
      53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph
      chromosome and its variant translocations and accurately quantify disease in CML
      at diagnosis and at all times after treatment, including cytogenetic remission.

PMID- 9558394
TI  - Prognostic value of numerical chromosome aberrations in multiple myeloma: A FISH
      analysis of 15 different chromosomes.
AB  - Recent observations indicate that chromosome aberrations are important prognostic
      factors in patients with multiple myeloma (MM) treated with high-dose
      chemotherapy. Nevertheless, the inherent problems of conventional cytogenetics
      have hampered the systematic evaluation of this parameter in series of patients
      treated with conventional chemotherapy. Fluorescence in situ hybridization (FISH)
      analysis is an attractive alternative for evaluation of numerical chromosomal
      changes. In the present study, we analyze the relationship between aneuploidies
      of 15 different chromosomes assessed by FISH and prognosis in a series of 63
      patients with MM treated with conventional chemotherapy. After a median follow-up
      of 61 months (range, 6 to 109), 49% of patients are still alive with a median
      survival of 33 months. The overall incidence of numerical chromosome
      abnormalities was 70%. This incidence significantly increased when seven or more
      chromosomes were analyzed (53 patients), reaching 81%. Trisomies of chromosomes
      6, 9, and 17 were associated with prolonged survival (P = .033, P = .035, and P =
      .026, respectively); by contrast, overall survival (OS) was lower in cases with
      monosomy 13 (as assessed by deletion of Rb gene, P = .0012). From the clinical
      point of view, loss of Rb gene was associated with a poor performance status; low
      hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase
      serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone
      lytic lesions; and advanced clinical stage. Other chromosome abnormalities such
      as trisomy of chromosome 9 and 17 were associated with good prognostic features
      including high hemoglobin levels, early clinical stage, beta2microglobulin less
      than 6 micro/mL, and low percentage of BMPC. A multivariate analysis for OS
      showed that S-phase PC greater than 3% (P = .010) and beta2microglobulin serum
      levels greater than 6 micro/mL (P = .024), together with monosomy of chromosome
      13 (P = .031) and nontrisomy of chromosome 6 (P = .048) was the best combination
      of independent parameters for predicting survival in patients with MM. According
      to these results, chromosomal analysis is of great use in patients with MM at
      diagnosis to have a correct prognostic evaluation for clinical decision making.

PMID- 9558395
TI  - Neutropenia associated with T-cell large granular lymphocyte leukemia: long-term
      response to cyclosporine therapy despite persistence of abnormal cells.
AB  - T-cell large granular lymphocyte (T-LGL) leukemia is clinically indolent, but is
      associated with severe neutropenia in approximately 50% of cases. The
      pathogenesis of the neutropenia is unclear. We report reversal of severe
      neutropenia associated with T-LGL leukemia in five patients treated with
      cyclosporine (CSA). All five had persistent neutrophil counts below 0.5 x
      10(9)/L, two had agranulocytosis, and four had recurrent infections. Increased
      populations of LGL were present in blood and marrow, with a T-LGL immunophenotype
      (CD3(+)CD8(+)CD16(+/-)CD56(+/-)CD57(+)) shown by multiparameter flow cytometry,
      and clonal T-cell receptor (TCR) gene rearrangements in two of two pretreatment
      blood samples studied. CSA was initiated at doses of 1 to 1.5 mg/kg orally every
      12 hours, with subsequent dose adjustments based on trough serum levels. Four
      patients attained normal neutrophil counts with CSA alone; one required addition
      of low-dose granulocyte-macrophage colony-stimulating factor. Time to attainment
      of 1.5 x 10(9)/L neutrophils ranged from 21 to 75 days. Attempts to taper and
      withdraw CSA resulted in recurrent neutropenia. Three patients have maintained
      normal neutrophil counts on continued CSA therapy for 2, 8, and 8.5 years. Two
      patients died 1.7 and 4.6 years after initiation of CSA despite normal neutrophil
      counts-one of metastatic melanoma and one of complications after aortofemoral
      bypass surgery. Despite resolution of neutropenia, increased populations of T-LGL
      cells have persisted in all patients during CSA therapy, as shown by morphology
      and flow cytometry and by the presence of clonal TCR gene rearrangements in four
      patients' posttreatment blood samples. We conclude that CSA is an effective
      therapy for neutropenia associated with T-LGL leukemia, and that resolution of
      neutropenia despite persistence of abnormal cells implies that CSA may inhibit T
      LGL secretion of yet unidentified mediators of neutropenia.

PMID- 9558397
TI  - Expression of the T-cell-specific tyrosine kinase Lck in normal B-1 cells and in
      chronic lymphocytic leukemia B cells.
AB  - Src family kinases play a key role in mitogenesis. The exquisitely tissue
      specific distribution of different Src family members suggests that a fine tuning
      of their expression might be a key prerequisite for cell homeostasis. We tested B
      cells from patients affected by B-cell chronic lymphocytic leukemia (B-CLL) for
      expression of Src family kinases. The T-cell-specific tyrosine kinase Lck was
      found to be expressed at significant levels in CLL B-cells. This finding could be
      accounted for either by ectopic expression of Lck in B-CLL or by specific
      expression of this kinase in normal B-1 cells, which are believed to be the
      normal counterpart of CLL B cells. To answer this question B cells from different
      sources, characterized by a different size of the B-1 subpopulation, were tested
      for Lck expression. The results show that Lck expression is a feature of CD5(+),
      B-1 cells, suggesting a potential role for Lck in the self-renewal capacity of
      this B-cell subpopulation and supporting the notion that B-1 cells are the subset
      undergoing oncogenic transformation in B-CLL. Furthermore, we show that the CD5(
      ), B-2 subpopulation, while normally lacking Lck expression, acquires the
      capacity to express Lck ectopically upon transformation by EBV.

PMID- 9558396
TI  - Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia:
      correlations with In vitro and In vivo chemoresponses.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) represents a neoplastic disorder
      caused primarily by defective programmed cell death (PCD), as opposed to
      increased cell proliferation. Defects in the PCD pathway also contribute to
      chemoresistance. The expression of several apoptosis-regulating proteins,
      including the Bcl-2 family proteins Bcl-2, Bcl-XL, Mcl-1, Bax, Bak, and BAD; the
      Bcl-2-binding protein BAG-1; and the cell death protease Caspase-3 (CPP32), was
      evaluated by immunoblotting using 58 peripheral blood B-CLL specimens from
      previously untreated patients. Expression of Bcl-2, Mcl-1, BAG-1, Bax, Bak, and
      Caspase-3 was commonly found in circulating B-CLL cells, whereas the Bcl-XL and
      BAD proteins were not present. Higher levels of the anti-apoptotic protein Mcl-1
      were strongly correlated with failure to achieve complete remission (CR) after
      single-agent therapy (fludarabine or chlorambucil) (P = .001), but the presence
      of only seven CRs among the 42 patients for whom follow-up data were available
      necessitates cautious interpretation of these observations. Higher levels of the
      anti-apoptotic protein BAG-1 were also marginally associated with failure to
      achieve CR (P = .04). Apoptosis-regulating proteins were not associated with
      patient age, sex, Rai stage, platelet count, hemoglobin (Hb) concentration, or
      lymph node involvement, although higher levels of Bcl-2 and a high Bcl-2:Bax
      ratio were correlated with high numbers (>10(5)/microL) of white blood cells
      (WBC) (P = .01; .007) and higher levels of Bak were weakly associated with loss
      of allelic heterozygosity at 13q14 (P = .04). On the basis of measurements of
      apoptosis induction by fludarabine using cultured B-CLL specimens, in vitro
      chemosensitivity data failed to correlate with in vivo clinical response rates (n
      = 42) and expression of the various apoptosis-regulating proteins. Although
      larger prospective studies are required before firm conclusions can be reached,
      these studies show the expression in B-CLLs of multiple apoptosis-regulating
      proteins and suggest that the relative levels of some of these, such as Mcl-1,
      may provide information about in vivo responses to chemotherapy. In vitro
      chemosensitivity data, however, do not appear to be particularly useful in
      predicting responses in B-CLL.

PMID- 9558398
TI  - 6q deletions in acute lymphoblastic leukemia and non-Hodgkin's lymphomas.
AB  - Deletions on the long arm of chromosome 6 are frequently found in acute
      lymphoblastic leukemia (ALL) and non-Hodgkin's lymphomas (NHL). We have used
      polymerase chain reaction analysis to study loss of heterozygosity of 16
      microsatellite markers on chromosome 6 in 74 ALL and 54 NHL patients. Our results
      show that deletions of 6q in ALL are more frequent than what has been reported in
      previous studies, occurring in at least 32% of the patients. The corresponding
      figure for NHL patients is 7%. Our results define a region of minimal deletion in
      ALL of less than 500 kb between markers D6S1709 and D6S434. The common region of
      deletion in NHL is located telomeric of this region. Thus, two different tumor
      suppressor genes on chromosome 6q seem to be relevant for the development of
      lymphoid malignancies.

PMID- 9558399
TI  - A strong expression of CD44-6v correlates with shorter survival of patients with
      acute myeloid leukemia.
AB  - CD44 is a ubiquitous cell-surface glycoprotein that displays many variant
      isoforms (CD44v) generated by alternative splicing of exons 2v to 10v. The
      expression of variant isoforms is highly restricted and correlated with specific
      processes, such as leukocyte activation and malignant transformation. We have
      herein studied CD44v expression in acute myeloid leukemia (AML) and, for
      comparison, in normal myelopoiesis. Protein expression of total CD44 and of CD44
      3v, -6v, and -9v isoforms has been measured using specific monoclonal antibodies
      and flow cytometry. The composition of variant exon transcripts has been analyzed
      by semi-quantitative reverse transcriptase-polymerase chain reaction followed by
      Southern hybridization with exon-specific probes. Our data show that (1) CD44-6v
      isoforms are expressed on 12.0% +/- 2.5% of normal CD34(+) cells; this expression
      is sharply upregulated through monopoiesis and, inversely, downregulated during
      granulopoiesis. Also, CD44-3v and CD44-9v isoforms are detected on 10% and 14% of
      normal monocytes, respectively. (2) Sixty-nine from a total of 95 AML patients
      display a variable proportion (range, 5% to 80%) of CD44-6v+ leukemic cells. (3)
      A shorter overall survival characterizes the group of AML patients displaying
      more than 20% of CD44-6v+ leukemic cells (8 months v 18 months, P < .02). These
      data suggest, for the first time, that the protein expression of CD44-6v
      containing isoforms may serve as a new prognostic factor in AML.

PMID- 9558400
TI  - Inhibition of BCR-ABL expression with antisense oligodeoxynucleotides restores
      beta1 integrin-mediated adhesion and proliferation inhibition in chronic
      myelogenous leukemia hematopoietic progenitors.
AB  - Chronic myelogenous leukemia (CML) is characterized by the continuous
      proliferation and abnormal circulation of malignant hematopoietic progenitors.
      This may be related to the unresponsiveness of CML progenitors to beta1 integrin
      adhesion receptor-mediated inhibition of progenitor proliferation by the marrow
      microenvironment. In hematopoietic cell lines, the BCR-ABL oncogene product,
      p210(BCR-ABL), interacts with a variety of cytoskeletal elements important for
      normal integrin signaling. We studied the role of p210(BCR-ABL) in abnormal
      integrin function in CML by evaluating the effect of inhibition of BCR-ABL
      expression with antisense oligodeoxynucleotides (AS-ODNs) on integrin-mediated
      adhesion and proliferation inhibition of malignant primary progenitors from CML
      marrow. Preincubation of CML CD34(+)HLA-DR+ (DR+) cells with breakpoint-specific
      AS-ODNs significantly increased adhesion of CML progenitors to stroma and
      fibronectin (FN). Pretreatment with breakpoint-specific ODNs also resulted in
      significant inhibition of CML progenitor proliferation after ligand or antibody
      mediated beta1 integrin engagement. Breakpoint-specific ODNs were significantly
      more effective in restoring CML progenitor adhesion and proliferation inhibition
      than control ODNs. BCR-ABL mRNA and p210(BCR-ABL) levels in CML CD34(+) cells
      were significantly reduced after incubation with breakpoint-specific AS-ODN.
      These studies indicate a role for BCR-ABL in abnormal circulation and defective
      integrin-dependent microenvironmental regulation of proliferation of CML
      hematopoietic progenitors.

PMID- 9558401
TI  - Raised neutrophil phospholipase A2 activity and defective priming of NADPH
      oxidase and phospholipase A2 in sickle cell disease.
AB  - Intermittent painful crises due to vasoocclusion are the major clinical
      manifestation of sickle cell disease (SCD), but subclinical episodes may also
      occur. There is sparse evidence for the involvement of neutrophils in the
      pathophysiology of SCD, but production of cytokines by the damaged endothelium
      might influence neutrophil function and modulate responses to subsequent cytokine
      exposure. In addition, the activation of neutrophils in the microcirculation
      could itself exacerbate vasoocclusion. To test whether neutrophil inflammatory
      responses were altered in SCD, neutrophil phospholipase A2 and NADPH oxidase
      activity in response to in vitro priming by granulocyte-macrophage colony
      stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) were
      measured both during and between painful crises. Resting levels of neutrophil
      phospholipase A2 activity in steady-state SCD (4.0% +/- 0. 5% of total cell
      radioactivity) were raised relative to control values (2.0% +/- 0.2%, n = 10, P =
      .008). There was no defect of agonist-stimulated phospholipase A2 or NADPH
      oxidase activity in steady-state SCD; however, the ability of phospholipase A2 to
      respond to priming with GM-CSF was attenuated to 63% +/- 17% of control values (n
      = 10, P = .04). Similarly, neutrophil NADPH oxidase activity after priming with
      GM-CSF and TNF-alpha was, respectively, 65% +/- 11% (n = 7, P = .03) and 57% +/-
      7% of control (n = 10, P = .007) in steady-state disease, and was further reduced
      during painful vasoocclusive crises to 34% +/- 9% and 25% +/- 3% of control for
      GM-CSF and TNF-alpha, respectively. These data were not explained by poor splenic
      function or any racial factor, as normal cytokine responses were seen in
      splenectomized patients in remission from Hodgkin's disease and in healthy Afro
      Caribbean subjects. Abnormal neutrophil cytokine priming responses were not
      observed in either patients with rheumatoid arthritis or iron-deficiency anemia.
      Our findings are indicative of an ongoing inflammatory state in SCD between
      painful crises involving neutrophil activation and an abnormality of cytokine
      regulated neutrophil function, which may compromise the host defenses against
      certain microorganisms.

PMID- 9558402
TI  - Galectin-3 activates the NADPH-oxidase in exudated but not peripheral blood
      neutrophils.
AB  - Galectin-3, a lactose-binding mammalian lectin that is secreted from activated
      macrophages, basophils, and mast cells, was investigated with respect to its
      ability to activate the human neutrophil NADPH-oxidase. The galectin-3-induced
      activity was determined with in vivo exudated cells (obtained from a skin
      chamber) and compared with that of peripheral blood neutrophils. Galectin-3 was
      found to be a potent activator of the NADPH-oxidase only in exudated neutrophils
      and the binding of galectin-3 to the surface of these cells was increased
      compared with peripheral blood cells. Different in vitro priming protocols
      resulting in degranulation were used to mimic the exudation process in terms of
      increasing the receptor exposure on the cell surface. Galectin-3 could induce an
      oxidative response similar to that in exudated cells only after a significant
      amount of the intracellular organelles had been mobilized. This increase in
      oxidative response was paralleled by an increased binding of galectin-3 to the
      surface of the cells. The major conclusion of the study is that galectin-3 is a
      potent stimulus of the neutrophil respiratory burst, provided that the cells have
      first experienced an extravasation process. The results also imply that the
      neutrophil response to galectin-3 could be mediated through receptors mobilized
      from intracellular granules, and we report the presence of galectin-3-binding
      proteins in such organelles.

PMID- 9558403
TI  - Reduced ex vivo interleukin-8 production by neutrophils in septic and nonseptic
      systemic inflammatory response syndrome.
AB  - Ex vivo cytokine production by circulating lymphocytes and monocytes is reduced
      in patients with infectious or noninfectious systemic inflammatory response
      syndrome. Very few studies have addressed the reactivity of polymorphonuclear
      cells (PMN). To analyze further the relative contribution of systemic
      inflammatory response syndrome alone or in combination with infection we studied
      the interleukin-8 (IL-8) production by PMN isolated from patients who had
      undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with
      sepsis. Cells were activated with either lipopolysaccharide (LPS) or heat-killed
      streptococci. Compared with healthy controls, the release of IL-8 by PMN in both
      groups of patients was significantly reduced whether activated by LPS,
      independently of its concentration and origin, or by heat-killed streptococci.
      These observations suggest that stressful conditions related to inflammation,
      independently of infection, rapidly dampened the reactivity of circulating PMN.
      We investigated whether the observed diminished reactivity of PMN might reflect
      an endotoxin tolerance phenomenon. Our in vitro experiments with PMN from healthy
      controls indicated that PMN could not be rendered tolerant stricto sensu.
      However, our data suggested that LPS-induced mediators such as IL-10 may be
      responsible for the observed anergy in patients.

PMID- 9558404
TI  - Mechanisms of transcription in eosinophils: GATA-1, but not GATA-2,
      transactivates the promoter of the eosinophil granule major basic protein gene.
AB  - Granule major basic protein (MBP) is expressed exclusively in eosinophils,
      basophils, and placental trophoblasts. To identify the cis-elements and
      transcription factors involved in regulating MBP expression, we subcloned 3.2 kb
      of sequence upstream of the exon 9 transcriptional start site (P2 promoter) and
      serial 5' deletions into the pXP2 luciferase reporter vector. An 80% decrement in
      promoter activity was obtained when MBP sequences between bp -117 to -67 were
      deleted. To identify transcription factors that bind to and transactivate through
      the bp -117 to -67 region, we first compared the upstream genomic sequences of
      human and murine MBP; a potential GATA binding consensus site was conserved in
      the 50-bp region between the two genes. To determine which GATA proteins bind
      this consensus site, we performed electrophoretic mobility shift assays (EMSAs),
      which showed that both GATA-1 and GATA-2 can bind to this consensus site. To
      determine the functionality of this site, we tested whether GATA-1 and GATA-2,
      either individually or in combination, can transactivate the MBP promoter in the
      Jurkat T cell line. Cotransfection with a GATA-1 expression vector produced 20
      fold augmentation of MBP promoter activity, whereas GATA-2 had no activity. In
      contrast, combined cotransfection of GATA-1 and GATA-2 decreased the ability of
      GATA-1 to transactivate the MBP promoter by approximately 50%. Our results
      provide the first evidence for a GATA-1 target gene in eosinophils, a negative
      regulatory role for GATA-2 in MBP expression, and possibly eosinophil gene
      transcription in general during myelopoiesis.

PMID- 9558405
TI  - Erythroid maturation and globin gene expression in mice with combined deficiency
      of NF-E2 and nrf-2.
AB  - NF-E2 binding sites, located in distant regulatory sequences, may be important
      for high level alpha- and beta-globin gene expression. Surprisingly, targeted
      disruption of each subunit of NF-E2 has either little or no effect on erythroid
      maturation in mice. For p18 NF-E2, this lack of effect is due, at least in part,
      to the presence of redundant proteins. For p45 NF-E2, one possibility is that NF
      E2-related factors, Nrf-1 or Nrf-2, activate globin gene expression in the
      absence of NF-E2. To test this hypothesis for Nrf-2, we disrupted the Nrf-2 gene
      by homologous recombination. Nrf-2-deficient mice had no detectable hematopoietic
      defect. In addition, no evidence was found for reciprocal upregulation of NF-E2
      or Nrf-2 protein in fetal liver cells deficient for either factor. Fetal liver
      cells deficient for both NF-E2 and Nrf-2 expressed normal levels of alpha- and
      beta-globin. Mature mice with combined deficiency of NF-E2 and Nrf-2 did not
      exhibit a defect in erythroid maturation beyond that seen with loss of NF-E2
      alone. Thus, the presence of a mild erythroid defect in NF-E2-deficient mice is
      not the result of compensation by Nrf-2.

PMID- 9558406
TI  - Comparative oxidation of hemoglobins A and S.
AB  - The mutant hemoglobin S (HbS) previously was reported to undergo accelerated
      autooxidation during incubation in vitro. However, subsequent observations have
      raised the possibility that this might be explained by adventitious association
      of molecular iron with HbS, rather than reflecting an inherent property of HbS.
      Using purified HbA and HbS obtained from genotypic HbAS donors, we found that the
      observed oxidation rate of HbS, but not of HbA, is indeed exaggerated by
      adventitious iron. This result suggests a preferential partitioning of molecular
      iron to HbS over HbA, which was further supported by experimentation. However,
      after elimination of this effect, there still remains a significant increase in
      inherent autooxidation rate for HbS. Physiologic oxidants (superoxide, peroxide,
      hydroxyl radical) and various Fe(III) chelates all stimulate oxidation of oxyHb,
      but they do so equivalently for HbA and HbS. Nevertheless, these mechanisms also
      would contribute to excessive biologic oxidation of HbS because the cytoplasm of
      sickle red blood cells, unlike that of normal cells, would be exposed to abnormal
      amounts of oxidants and low-molecular-weight iron compounds.

PMID- 9558407
TI  - Mouse hypoxia-inducible factor-1alpha is encoded by two different mRNA isoforms:
      expression from a tissue-specific and a housekeeping-type promoter.
AB  - Hypoxic induction of erythropoietin (Epo) and other oxygen-dependent genes is
      mediated by the hypoxia-inducible factor-1 (HIF-1), a heterodimeric
      transactivator consisting of an alpha and a beta subunit. We previously found
      that the mouse gene encoding HIF-1alpha harbors two alternative first exons (I.1
      and I.2), giving rise to two different HIF-1alpha mRNA isoforms. Here, we show by
      RNase protection analysis that the exon I.1-derived mRNA isoform is
      differentially expressed in mouse tissues, being highest in kidney, tongue,
      stomach, and testis, but undetectable in liver, whereas the exon I.2 mRNA isoform
      is ubiquitously expressed. Sequence and methylation analysis showed that, in
      contrast to exon I.1, exon I.2 resides within a region showing typical features
      of a CpG island, known to be associated with the 5' end of housekeeping genes. We
      identified a 232-bp minimal exon I.2 promoter that strongly induced reporter gene
      expression in mouse L929 fibroblasts and Hepa1 hepatoma cells. In contrast to
      L929 cells, the exon I.1 promoter was inactive in Hepa1 cells and hypoxic
      exposure (1% O2) markedly reduced exon I.2 promoter activity in Hepa1 cells.
      Prolonged exposure of mice to hypoxia (7.5% O2 for up to 72 hours) also caused a
      decrease in liver HIF-1alpha mRNA, whereas aldolase mRNA levels increased. These
      findings might be related to the relatively low Epo levels in the adult liver.

PMID- 9558408
TI  - Identification of patients who may benefit from prophylactic immunotherapy after
      bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte
      recovery early after transplantation.
AB  - Two hundred and one patients (median age, 29 years) with acute myeloid leukemia
      (AML) underwent bone marrow transplantation (BMT) from HLA-identical sibling
      donors after conditioning with melphalan-total-body irradiation (TBI) (57%),
      cyclophosphamide-TBI (35%), or chemotherapy alone (8%). Graft-versus-host disease
      (GVHD) prophylaxis included cyclosporine alone (68%), cyclosporine-methotrexate
      (26%), or T-cell depletion (6%). The probability of relapse was calculated as a
      function of the absolute lymphocyte count (10(9)/L) on days 27 to 30
      posttransplant (<0.1 v >/=0.1, <0.2 v >/=0.2, and <0.3 v >/=0.3). In each of
      these 12 comparisons, the probability of relapse was higher for the group with
      the lower lymphocyte count. Because the difference was most significant (P =
      .004) for an absolute lymphocyte count of <0.2 on day 29 (3-year relapse
      probability, 42%) versus >/= 0.2 (16%), this variable was included in a Cox model
      to determine factors independently affecting relapse. Multivariate analysis
      showed that conditioning regimens other than melphalan-TBI, a low lymphocyte
      count on day 29, French-American-British (FAB) subtypes M4-7, and a nucleated
      cell dose of > 2.42 x 10(8)/kg was associated with a higher risk of relapse. We
      conclude that slow lymphocyte recovery after allogeneic BMT, to < 0.2 x 10(9)/L
      29 days in this analysis, appears to be associated with a higher risk of relapse
      in patients with AML. This group of patients may benefit from posttransplant
      immune manipulations such as abbreviated GVHD prophylaxis, or donor cell or
      cytokine administration to enhance graft-versus-leukemia reactions to reduce
      relapse.

PMID- 9558409
TI  - Efficient retroviral-mediated gene transfer to human cord blood stem cells with
      in vivo repopulating potential.
AB  - Recent studies have shown efficient gene transfer to primitive progenitors in
      human cord blood (CB) when the cells are incubated in retrovirus-containing
      supernatants on fibronectin-coated dishes. We have now used this approach to
      achieve efficient gene transfer to human CB cells with the capacity to regenerate
      lymphoid and myeloid progeny in nonobese diabetic (NOD)/severe combined
      immunodeficiency (SCID) mice. CD34(+) cell-enriched populations were first
      cultured for 3 days in serum-free medium containing interleukin-3 (IL-3), IL-6,
      granulocyte colony-stimulating factor, Flt3-ligand, and Steel factor followed by
      two 24-hour incubations with a MSCV-NEO virus-containing medium obtained under
      either serum-free or serum-replete conditions. The presence of serum during the
      latter 2 days made no consistent difference to the total number of cells, colony
      forming cells (CFC), or long-term culture-initiating cells (LTC-IC) recovered at
      the end of the 5-day culture period, and the cells infected under either
      condition regenerated similar numbers of human CD34(+) (myeloid) CFC and human
      CD19(+) (B lymphoid) cells for up to 20 weeks in NOD/SCID recipients. However,
      the presence of serum increased the viral titer in the producer cell-conditioned
      medium and this was correlated with a twofold to threefold higher efficiency of
      gene transfer to all progenitor types. With the higher titer viral supernatant,
      17% +/- 3% and 17% +/- 8%, G418-resistant in vivo repopulating cells and LTC-IC
      were obtained. As expected, the proportion of NEO + repopulating cells determined
      by polymerase chain reaction analysis of in vivo generated CFC was even higher
      (32% +/- 10%). There was no correlation between the frequency of gene transfer to
      LTC-IC and colony-forming unit-granulocyte-macrophage (CFU-GM), or to NOD/SCID
      repopulating cells and CFU-GM (r2 = 0.16 and 0.17, respectively), whereas values
      for LTC-IC and NOD/SCID repopulating cells were highly and significantly
      correlated (r2 = 0.85). These findings provide further evidence of a close
      relationship between human LTC-IC and NOD/SCID repopulating cells (assessed using
      a >/= 6-week CFC output endpoint) and indicate the predictive value of gene
      transfer measurements to such LTC-IC for the design of clinical gene therapy
      protocols.

PMID- 9558410
TI  - Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of
      marrow engraftment in a canine model.
AB  - Primary graft rejection after marrow transplantation occurs more frequently in
      patients receiving HLA-haploidentical compared with HLA-identical sibling
      transplants. Both human and experimental animal data suggest that the cells
      responsible for this phenomenon are either host natural killer (NK) cells, T
      cells, or both. To investigate the mechanisms of graft rejection, we have
      developed a canine model of marrow transplantation, which uses DLA-nonidentical
      unrelated donors in the absence of postgrafting immunosuppression. In this model
      most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy
      total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can
      be facilitated when the recipients are pretreated with monoclonal antibody (MoAb)
      S5, which recognizes CD44. In this report, we extended these observations by
      first cloning the canine CD44 and, next, mapping the epitope recognized by S5,
      which was located in a region conserved among human and canine CD44 and was
      distinct from the hyaluronan binding domain. However, in vitro binding of S5
      caused a conformational change in CD44, which allowed increased hyaluronan
      binding. Then, we reexamined the in vivo model of marrow transplantation and
      compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and
      S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical
      unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The
      enhanced in vivo effect was not related to differences in the MoAbs' avidities,
      since both S5 and IM7 had equivalent binding to CD44, but most likely related to
      the specific epitope that S5 recognizes. Thus, this study shows that the effect
      of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if
      one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one
      cannot assume that any anti-CD44 would work.

PMID- 9558411
TI  - Low transplant mortality in allogeneic bone marrow transplantation for acute
      myeloid leukemia: a randomized study of low-dose cyclosporin versus low-dose
      cyclosporin and low-dose methotrexate.
AB  - Sixty patients undergoing allogeneic bone marrow transplant for acute myeloid
      leukemia (AML) in first remission (CR1; n = 49) or more advanced phase (n = 11)
      were entered in a prospective trial of graft-versus-host disease (GvHD)
      prophylaxis: low-dose cyclosporin A (IdCSA; 1 mg/kg/d from day -1 to +20 day; n =
      28) or IdCSA plus low-dose methotrexate (IdMTX; 10 mg/m2 for day +1, 8 mg/m2 for
      days +3, +6, and +11; n = 32). Primary end points were acute GvHD (aGvHD) and
      transplant-related mortality (TRM); secondary end points were relapse and
      survival. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and
      fractionated total body irradiation (3.3 Gy/d for 3 consecutive days). The
      actuarial risk of developing aGvHD grade II-III was 61% for IdCSA alone and 34%
      for IdCSA + IdMTX (P = .02). The actuarial risk of TRM at 1 year was 11% versus
      13%, respectively, and older patients (>/= 29 years) had higher TRM than younger
      patients (22% v 5%, P = .01). The age effect was significant in the IdCSA group
      (P = .04) but not in the IdCSA + IdMTX group (P = .1). The median follow-up is
      4.4 years, with an overall actuarial survival of 78% for CR1 patients and 36% for
      patients with advanced disease. For patients in CR1 the outcome of the two
      regimens was as follows: survival 77% versus 80% (P = .6), relapse 20% versus 9%
      (P = .1), and TRM 13% versus 17% (P = .6). This study suggests that TRM can be
      reduced in AML patients undergoing allogeneic marrow transplants with a mild
      conditioning regimen and low-dose immunosuppression, and this translates in a 78%
      5-year survival for CR1 patients. Beyond CR1 the major obstacle remains leukemia
      relapse, which is not prevented by low-dose in vivo immunosuppression.

PMID- 9558412
TI  - A multicenter study of platelet recovery and utilization in patients after
      myeloablative therapy and hematopoietic stem cell transplantation.
AB  - An observational study was conducted at 18 transplant centers in the United
      States and Canada to characterize the platelet recovery of patients receiving
      myeloablative therapy and stem cell transplantation and to determine the clinical
      variables influencing recovery, determine platelet utilization and cost, and
      incidence of hemorrhagic events. The study included 789 evaluable patients
      transplanted in 1995. Clinical, laboratory, and outcome data were obtained from
      the medical records. Variables associated with accelerated recovery in
      multivariate models included (1) higher CD34 count; (2) higher platelet count at
      the start of myeloablative therapy; (3) graft from an HLA-identical sibling
      donor; and (4) prior stem cell transplant. Variables associated with delayed
      recovery were (1) prior radiation therapy; (2) posttransplant fever; (3) hepatic
      veno-occlusive disease; and (4) use of posttransplant growth factors. Disease
      type also influenced recovery. Recipients of peripheral blood stem cells (PBSC)
      had faster recovery and fewer platelet transfusion days than recipients of bone
      marrow (BM). The estimated average 60-day platelet transfusion cost per patient
      was $4,000 for autologous PBSC and $11,000 for allogeneic BM transplants. It was
      found that 11% of all patients had a significant hemorrhagic event during the
      first 60 days posttransplant, contributing to death in 2% of patients. In
      conclusion, clinical variables influencing platelet recovery should be considered
      in the design and interpretation of clinical strategies to accelerate recovery.
      Enhancing platelet recovery is not likely to have a significant impact on 60-day
      mortality but could significantly decrease health care costs and potentially
      improve patient quality of life.

PMID- 9558413
TI  - Oligoclonal protein bands and Ig isotype switching in multiple myeloma treated
      with high-dose therapy and hematopoietic cell transplantation.
AB  - Multiple myeloma (MM) is usually characterized by production of a single serum
      monoclonal protein of constant isotype and light-chain restriction. Multiple Ig
      isotypes and isotype switches, which are rare in untreated patients, are reported
      to be more common in patients undergoing myeloablative therapy. These additional
      protein bands, detected by immunofixation electrophoresis (IFE), could be due to
      altered paraprotein production by the malignant plasma cell clone or oligoclonal
      Ig production during recovery of B-cell function after myeloablative therapy. We
      analyzed abnormal protein bands (APB), distinct from the presenting paraprotein,
      in 550 patients receiving high-dose therapy with autologous hematopoietic cell
      transplantation at a single institution. Fifty-five patients (10%) had APB, 48
      had oligoclonal bands (OB), and 23 had an apparent isotype switch (IS) on IFE (16
      had both OB and IS). Morphologic and flow cytometric examination of bone marrow
      in 17 patients with IS showed no evidence of a clonal plasma cell isotype switch.
      Patients with APB had significantly higher complete response to therapy (67% v
      37%, P = .001). To assess the independent prognostic relevance of APB, a
      multivariate analysis was performed among 471 patients surviving at least 12
      months from first transplant (all patients developing APB had done so by 12
      months from first transplant). APB (in 50 patients) was a favorable feature for
      both event-free (rank 3, P = .004) and overall survival (rank 3, P = .0005). We
      propose that OB and IS are likely to be due to recovery of Ig production rather
      than alterations in the biology of the malignant plasma cell clone.

PMID- 9558414
TI  - Congenital anhaptoglobinemia versus acquired hypohaptoglobinemia.

PMID- 9558415
TI  - Community pharmacy strives for continuity of care.

PMID- 9558416
TI  - Oral naratriptan approved for migraine attacks.

PMID- 9558417
TI  - Spike in managed care enrollment curbed employer health costs in 1997, survey
      shows.

PMID- 9558418
TI  - Report identifies research priorities for improving end-of-life care.

PMID- 9558419
TI  - Accessing investigational anticancer agents outside of clinical trials.

PMID- 9558420
TI  - Helping HIV-infected patients at the clinic.

PMID- 9558421
TI  - Change of perspective.

PMID- 9558422
TI  - The vertically integrated pharmacy department.
AB  - Pharmacy's challenges and opportunities during a transition from a traditional
      hospital to an integrated health system are discussed with reference to the
      experience of a medical center in Vancouver, Washington. When a traditional
      hospital makes the transition to an integrated health system, pharmacy directors
      must consider how the core business will be affected, how pharmacy can add value,
      and how to best apply the skills of the pharmacy department. A well-trained staff
      that shares a view of the new organization and that can think outside the
      traditional hospital paradigm is required. New health systems will focus on
      quality-related outcomes at low cost and on disease management. Partnerships
      between providers and health care staff will be beneficial. To compete for
      capitated contracts, health systems will need to deliver services other than
      acute care to a broad geographic area, and primary care will be more prominent.
      There will be a shift toward outpatient services, and pharmacy departments will
      be under increasing pressure to develop outpatient pharmaceutical services.
      Pharmacy departments will also need to develop treatment guidelines for
      outpatients and to better manage drug costs by working with new business clients,
      improving continuity of care, increasing patients' access to care, having
      pharmacists provide hospice care, and implementing remote prescription-order
      entry. New health systems will need to have a clear understanding of how their
      core business is changing; the organizational strategy of a health system must
      include effective communication of change to staff members with the goal of
      overcoming traditional thinking.

PMID- 9558423
TI  - Catecholamines and their blockade in congestive heart failure.
AB  - The hemodynamic effects of sympathetic nervous system stimulation and the
      benefits of catecholamine blockade in patients with congestive heart failure
      (CHF) are discussed. Prolonged stimulation of the sympathetic nervous system
      promotes disease progression in patients with CHF. The level of circulating
      norepinephrine is the factor most closely correlated with prognosis. Long-term
      catecholamine stimulation of beta-receptors in the myocardium reduces the ability
      of catecholamines to improve cardiac contractility. CHF patients have higher
      vascular resistance (afterload) than healthy persons, increasing the strain on
      the heart. Also, beta 1-adrenergic activity stimulates renin release, which is
      deleterious in CHF. Clinical trials suggest that long-term (greater than one
      month), carefully dose-adjusted therapy with beta-blockers improves symptoms,
      ventricular ejection fraction, exercise time, and quality of life in patients
      with CHF, but it is unclear whether beta-blockers reduce mortality. Some patients
      cannot tolerate even the lowest starting dosages of beta-blockers, and withdrawal
      of these agents may result in clinical and hemodynamic deterioration. Carvedilol,
      which has beta-blocking, alpha-blocking, and antioxidant properties, is
      associated with a reduction in hospitalizations and symptoms and improvements in
      ejection fraction it also appears to reduce mortality, although confirmatory
      studies are needed. Initiation of carvedilol therapy can cause symptomatic and
      hemodynamic worsening in the short term, and some patients cannot tolerate it.
      Adrenergic blocking agents are important components of therapy for CHF.
      Carvedilol may prove useful in reducing symptoms and improving survival in these
      patients.

PMID- 9558424
TI  - Drug stability and pyridine generation in ceftazidime injection stored in an
      elastomeric infusion device.

PMID- 9558425
TI  - FDA comments on activities in states concerning narrow-therapeutic-index drugs.

PMID- 9558426
TI  - In favor of Coumadin over generic warfarin.

PMID- 9558427
TI  - Reflections on generic warfarin.

PMID- 9558428
TI  - Somatropin administration by three drug-delivery systems.

PMID- 9558429
TI  - Oral syringe for extemporaneously preparing doses.

PMID- 9558430
TI  - [The central vein catheter--a (simple) routine measure?].

PMID- 9558431
TI  - [Pharmacologic aspects of polyunsaturated fatty acids in parenteral nutrition].
AB  - Despite immense progress in intensive-care medicine, mortality rates of 30-70% in
      sepsis and SIRS are still an unresolved problem. Particularly the failure of
      respiratory and other vital functions is a major cause of death. Besides
      infectious stimuli (viruses, bacteria, fungi) a variety of non-infectious
      triggers (tissue damage, immune complexes, complement activation, etc.) can
      initiate the development of organ failure. These inflammatory reactions aim
      physiologically towards inactivation and removal of the stimulating agents as
      well as the induction of reparative processes. In states of prolonged activation
      of humoral and cellular mediator systems the natural host defence mechanisms
      react in an uncontrolled manner causing tissue damage and organ failure. So far
      there are no efficient therapeutic strategies to influence these complex
      inflammatory reactions. In the development of SIRS and sepsis, pro-inflammatory
      lipid mediators play a crucial role. Omega-3-fatty acids (omega-3-PUFAs) have
      shown anti-inflammatory and antithrombotic properties in a great number of
      experimental and clinical studies. These effects seem to be related to the uptake
      of eicosapentaenoic acid (EPA) into cellular membrane lipid pools and its
      subsequent metabolisation. After inflammatory activation EPA is released besides
      arachidonic acid (AA) and competes with AA for metabolisation via the cyclo- and
      lipoxygenase pathway. Compared to AA the derivatives of EPA have less pro
      inflammatory and chemotactic characteristics. With regard to prophylactic and
      therapeutic consequences it appears reasonable to supplement omega-3-PUFAs to
      attenuate the inflammatory response by modulating the generation of lipid
      mediators during inflammation.

PMID- 9558433
TI  - [Aloys Martin and the Society of German Physicians in Paris].
AB  - The news about the discovery of the anaesthetic properties of ether swept rapidly
      from America to Europe. The first informations concerning this topic reached
      England in late fall of 1846 and after that came to France and especially Paris.
      The German physician Aloys Martin from Munich who was living in Paris at that
      time was largely responsible for conveying the news about these new findings in
      medical science to the German-speaking nations. Controversial discussions
      concerning the anaesthetic properties of ether developed among the members of
      various scientific circles right after the news from America had reached the city
      -and many members of the "Verein Deutscher Aerzte in Paris" (Association of
      German Physicians in Paris) took part in them, Martin then was one of the club's
      most active members and repeatedly reported on the new method as a correspondent
      for the widely read "Augsburger Allgemeine Zeitung": Documents discovered
      recently at the archives of the "Leopoldinisch-Carolinischen Akademie" of Halle
      provide an interesting insight into this association, whose members tried to find
      out more about the anaesthetic properties and side effects of ether carrying out
      a series of well appreciated self-experiments in the spring of 1847. The
      following text reports on the history of the "Verein Deutscher Aerzte in Paris"
      which has largely fallen into oblivion and emphasizes the importance of Aloys
      Martin whose name is strongly attached to the spread of the use of ether
      throughout the German-speaking countries.

PMID- 9558432
TI  - [Electrophysiologic arousal reactions during sufentanil-/isoflurane anesthesia].
AB  - PURPOSE: There is controversy about relevant EEG signal changes indicating
      adequate or inadequate anaesthesia. Differences of drug-induced and nociceptive
      mediated signal changes have not been studied in detail. The present study
      investigates whether signal changes during decreases of depth of anaesthesia due
      to surgical stimulation depend on different isoflurane concentrations during
      sufentanil anaesthesia. METHODS: Following IRB approval and written informed
      consent 28 patients (ASA: I; age 43 +/- 11 y) scheduled for elective abdominal
      surgery were included in the study. Anaesthesia: propofol (2.0 mg/kg) and
      sufentanil (1.0 micrograms/kg). Following endotracheal intubation (vecuronium 0.1
      mg/kg) patients were normoventilated (P(ET)CO2: 36-38 mmHg). Randomly assigned to
      steady-state anaesthesia (group 1: P(ET)Isoflurane 0.2%, (14n); group 2:
      P(ET)Isoflurane 0.6%, (14n) during the start of surgery. Monitoring: heart rate
      (HF), mean arterial blood pressure (MAP), P(ET)CO2, arterial oxygen saturation
      and rectal temperature. EEG (16 channels referenced to Cz; CATEEM, Medisyst,
      Linden) recorded 5 min before until 10 min after the start of surgery. EEG
      analysis (FFT: 4s, 256/s, 0.45-35.0 Hz): topographical distribution of power
      spectral densities (delta, theta, alpha 1, and alpha 2). Artifact control: ECG
      and EOG. RESULTS: Surgical stimulation resulted in increases of MAP in both
      groups (p < 0.05 vs BL), whereas HR was only slightly affected in group 2 when
      compared with BL. Other variables except of EEG data did not change over time. In
      group 1 (0.2% isoflurane) surgical stimulation resulted in decreases of delta
      over the whole cortex (F2, C3, P3, O1) and in marked increases of alpha
      predominantly at central leads (C3)(p < 0.05 vs BL). In group 2 (0.6% isoflurane)
      nociceptive stimulation was associated with decreases of faster waves (alpha:
      F3)(p < 0.05 vs BL) and increases in delta at fronto-central areas (F3, C3)(p <
      0.05 vs BL). CONCLUSIONS: EEG recordings are useful in assessing pharmacodynamic
      drug effects. In contrast, intraoperative EEG recordings have a low correlation
      to clinical signs of changes in the anaesthetic state. Previous studies
      demonstrate paradoxical EEG-arousal reactions during isoflurane anaesthesia. The
      present data suggest that classical or even paradoxical EEG arousal due to
      nociceptive stimulation may depend on the isoflurane concentration. It seems
      reasonable that the ascending reticular formation is functionally blocked by
      isoflurane in a dose-dependent manner.

PMID- 9558434
TI  - [Control of the position of the central venous catheter--problems in choice of
      methods].

PMID- 9558435
TI  - [Development and current status of electrocardiographic position control of the
      central venous catheter].

PMID- 9558436
TI  - [Control of central venous catheter position by ECG recording with the guide
      wire].

PMID- 9558437
TI  - [ECG control of the position of the central venous catheter using the Seldinger
      guide wire: clinical and economic aspects].

PMID- 9558438
TI  - [The cava-catheter from the medico-legal viewpoint].

PMID- 9558439
TI  - [Is the laryngeal mask a device for preclinical resuscitation?--Pro].

PMID- 9558440
TI  - [Is the laryngeal mask a device for preclinical resuscitation?--Contra].

PMID- 9558441
TI  - [Successful resuscitation after bolus injection of tissue-type plasminogen
      activator in emergency admission].
AB  - We report on a 30-year old female patient with suspected fulminant pulmonary
      embolism and cardiac arrest following ambulatory arthroscopy nine days before the
      event. After 15 minutes of unsuccessful cardiopulmonary resuscitation (CPR) on
      the ambulance the patient was transferred to the emergency unit of a hospital and
      was treated with bolus injection of 50 mg t-PA initially and 50 mg over the next
      two hours. Five minutes after the initial bolus the circulation could be
      stabilised and the patient could be extubated the next morning. The patient did
      not present any neurological deficit on the day of discharge nor did she show any
      bleeding complications. The time elapsing from notice to emergency service to
      arrival at hospital was about 35 minutes. DISCUSSION: In patients with massive
      and life-threatening pulmonary embolism thrombolysis offers an opportunity to
      manage this critical situation. Due to the serious prognosis of these patients
      the potential benefit of thrombolysis outweighs the lack of preceding diagnostic
      procedures and the risk of potential side-effects. CONCLUSION: In the light of an
      excellent outcome of this patient thrombolytic therapy with t-PA appears to be
      justified under continued CPR if fulminant pulmonary embolism is suspected.

PMID- 9558442
TI  - Neither castration nor steroid-replacement change the apparent molecular size of
      FSH in the sheep pituitary.
AB  - Gonadal steroids alter the apparent molecular size of intrapituitary Follicle
      Stimulating Hormone (FSH) in rats and monkeys as well as increase the percentage
      of acidic FSH isohormones in sheep. Hence, we hypothesized that the molecular
      size of ovine (o) FSH would be increased by gonadal steroids. Extracts of
      pituitaries from rams and wethers, as well as, from wethers which had been
      implanted with dihydrotestosterone (DHT), 17 beta-estradiol (E2) or both steroids
      (n = 4-6 per treatment group) were subjected to analytical gel permeation
      chromatography using Sephadex g-100 Superfine. FSH concentrations in
      chromatographic fractions were determined by radioimmunoassays. Although FSH in
      pituitaries of non-implanted wethers eluted slightly earlier (i.e. larger) than
      FSH in pituitaries from E2-implanted wethers as evaluated by distribution
      coefficients (Kds) during chromatography (P < 0.05), gonadal steroids did not
      consistently increase Kds but tended to decrease them. When Kds were extrapolated
      to apparent molecular weights using a series of standard proteins (bovine serum
      albumin (bSA), ovalbumin (OA), carbonic anhydrase (CA) and cytochrome c (CC))
      that were included in each chromatogram, the differences between treatment groups
      were not statistically significant (P > 0.05). Thus, in contrast to rats and
      monkeys, neither castration nor steroid-replacement appears to alter the
      molecular size of FSH in the sheep pituitary as evaluated by analytical gel
      permeation chromatography.

PMID- 9558443
TI  - Unilateral spontaneous abdominal cryptorchidism: structural and ultrastructural
      study of sperm morphology.
AB  - Sperm morphology of three healthy boars and three boars with spontaneous
      abdominal cryptorchidism in the right testis has been evaluated by light
      microscopy. For each boar, two ejaculates have been analysed, corresponding to
      semen collections at the ages of 6.5 months (first collection) and 8 months
      (seventh collection). A comparative study of the sperm malformations present in
      the seventh semen collection between the healthy boars and the unilateral
      abdominal cryptorchid boars has also been performed by light microscopy. Sperm
      malformations of the seventh semen collection from the unilateral abdominal
      cryptorchid boars have been examined by scanning and transmission electron
      microscopy. The frequency of mature spermatozoa, immature spermatozoa, aberrant
      spermatozoa and detached heads maintained normals values in the first and the
      seventh semen collection from the unilateral abdominal cryptorchid boars. The
      comparative study of sperm abnormalities in the seventh semen collection between
      the cryptorchid boars and the healthy boars indicated that the unilateral
      abdominal cryptorchid boars had a significantly higher frequency of primary
      abnormalities, and a significantly lower frequency of secondary abnormalities.
      Some primary abnormalities, such as crater defect, knobbed acrosome defect,
      nuclear crests and abaxial tails were only observed in the unilateral abdominal
      cryptorchid boars. It was concluded that unilateral abdominal cryptorchidism
      provokes disturbances in the late stages of spermiogenesis, at testicular level.
      Alterations in the sperm maturation process at epididymal level were not found.

PMID- 9558445
TI  - Adverse effects of nonsteroidal anti-inflammatory drugs on the gastrointestinal
      system.
AB  - Two enzymes, cyclo-oxygenase (COX) and 5-lipoxygenase, act upon arachidonic acids
      to produce prostaglandins and leukotrienes. Inhibition of COX-2 by non-steroidal
      anti-inflammatory drugs (NSAIDs) lowers synthesis of proinflammatory
      prostaglandins and produces analgesia. COX-2 is highly inducible by endotoxin, IL
      1, hypoxia, epidermal growth factor (EGF), benzo[a]pyrene, and transforming
      growth factor beta 1(TGF-beta 1). COX-1 in constitutively expressed. Conventional
      NSAIDs also inhibit the synthesis of cytoprotective prostaglandins by COX-1 in
      the gastrointestinal tract. Surplus arachidonic acids accumulate and enhance the
      generation of leukotrienes via the lipoxygenase pathway inducing neutrophil
      adhesion to endothelium and vasoconstriction. The NSAIDs harboring a carboxyl
      group also inhibit oxidative phosphorylation (OXPHOS) lowering adenosine
      triphosphate (ATP) generation leading to loss of mucosal cell tight junctions and
      increased mucosal permeability. Administration of NSAIDs that do not interfere
      with OXPHOS, and concomitant use of prostaglandin analogues to restore
      cytoprotection reduces complications of NSAID use. However, no NSAID that lacks
      potential for serious gastrointestinal toxicity is currently available. Selective
      inhibitors of COX-2 and 5-lipoxygenase are newer, promising drugs. Surprisingly,
      COX-2 null mice are able to mount an inflammatory response, suffering however,
      from kidney dysfunction and a shortened life span. Results of clinical studies on
      the long-term use of NSAID drugs such as selective inhibitors are still pending.

PMID- 9558444
TI  - A role for lipoxygenase metabolites of arachidonic acid in porcine ovulation.
AB  - Prostaglandins, products of arachidonic acid via the cyclooxygenase pathway, are
      essential to the porcine ovulatory process in that inhibition of their synthesis
      results in ovulation failure. Studies in the rat have shown that ovulation is
      also preceded by a rise in three ovarian hydroxyeicosatetraenoic acids, products
      of the lipoxygenase pathway, and inhibition of this pathway also inhibits
      ovulation. Experiments were designed, using a pregnant mare serum
      gonadotropin/human chorionic gonadotropin (hCG)-treated prepuberal gilt model, to
      measure pre-ovulatory changes in follicular fluid concentrations of 15
      hydroxyeicosatetraenoic acid (15-HETE), and to compare the effects of
      indomethacin and nordihydroguaiaretic acid (NDGA) on ovulation in the pig and on
      15-HETE and prostaglandin F2 alpha synthesis both in vivo and in vitro.
      Follicular fluid concentrations of 15-HETE were elevated significantly just prior
      to the expected time of ovulation (40 h after hCG). When indomethacin (10 mg) was
      injected into the ovarian stalk at 24 h after hCG, follicular fluid
      concentrations of both 15-HETE and prostaglandin F2 alpha were lower (P < 0.01)
      than controls at 40 h and ovulation rate was suppressed (P < 0.01). When NDGA (5
      mg) was administered in the same manner, ovulation rate was suppressed (P <
      0.01), but the levels of 15-HETE and prostaglandin F2 alpha were not altered.
      Synthesis of 15-HETE by cultured granulosa and theca interna cells was reduced by
      the presence of NDGA (1 mg/ml), whereas indomethacin (100 ng/ml) lowered 15-HETE
      production in theca interna cells only. These results clearly demonstrate that
      indomethacin can block the lipoxygenase as well as the cyclooxygenase pathways,
      depending on the dose used, and suggest that lipoxygenase metabolites of
      arachidonic acid are involved in the ovulatory process in the pig.

PMID- 9558446
TI  - Abnormal proinsulin levels in thyroid dysfunction measured by a sensitive
      proinsulin immunochemiluminoassay.
AB  - Abnormalities of carbohydrate metabolism in hyperthyroid patients have been long
      noted. Elevated proinsulin level is considered as an early marker of B-cell
      impairment. Proinsulin levels in hyperthyroid patients decreased after
      antithyroid drug therapy. However, proinsulin in hypothyroid patients was only
      rarely reported, and the difference was only demonstrated after glucose
      stimulation-there was a greater response of proinsulin secretion after thyroxine
      therapy-and the basal fasting proinsulin level was not different after therapy.
      One of the reasons might be that the assay was not sensitive enough to detect the
      change of basal proinsulin levels in patients with hypothyroidism after therapy.
      A newly developed immunochemiluminometric assay of proinsulin was used to
      demonstrate that the suppressed proinsulin level increased after thyroxine
      therapy in hypothyroid patients (4.2 +/- 2.4 vs. 10.0 +/- 5.6 pmol/L, p < 0.05; n
      = 7). On the other hand, our study also confirmed that the proinsulin levels
      decreased in hyperthyroid patients after antithyroid therapy by methimazole (27.8
      +/- 26.0 vs. 15.8 +/- 15.7 pmol/L, p < 0.05; n = 12). In conclusion, proinsulin
      increased in hypothyroid patients after thyroxine therapy and decreased in
      hyperthyroid patients after methimazole therapy. The results demonstrated there
      is a high correlation between thyroid function and B-cell function in hypothyroid
      as well as hyperthyroid patients.

PMID- 9558447
TI  - Two sensitive immunometric assays for serum thyroid stimulating hormone
      evaluated.
AB  - This study was conducted to evaluate the analytical performance (functional
      sensitivity, reproducibility, parallelism, and accuracy) of two recent commercial
      kits marketed as third generation immunometric assays for measuring serum thyroid
      stimulating hormone (TSH). One assay is automated; the other is manual. Accuracy
      by method comparisons was evaluated using 86 patient samples assayed by an
      established third generation immunometric assay as the comparative method. The
      new assays met the third generation criterion for functional sensitivity (CV < or
      = 20 percent at TSH < or = 0.02 mIU/L), were reproducible (CVs < 11 percent), and
      measured serum TSH in parallel with the calibrator curves. Linear regression
      analysis of the intermethod comparison data showed highly correlated (R > .095)
      results; however, the regression slopes were non-unity, indicating patient sample
      results were not transferable between methods. Clinical laboratories choosing a
      third generation TSH assay should validate the performance characteristics of the
      selected method to ensure reliable results for patient care.

PMID- 9558448
TI  - Pneumocystis carinii pneumonia diagnosed by non-induced sputum stained with a
      direct fluorescent antibody.
AB  - Non-induced expectorated sputum (NIS) stained with tinctorial stains is not
      considered useful in the diagnosis of Pneumocystis carinii pneumonia (PCP). The
      diagnostic yield of NIS was evaluated in human immunodeficiency virus (HIV)
      infected patients, when stained with a more sensitive direct fluorescent antibody
      for PCP-direct fluorescent antibody (PC-DFA). A retrospective analysis was
      carried out on fifty-five HIV-infected patients with PCP, who had NIS submitted
      for staining with PC-DFA. Thirty had positive NIS with PC-DFA and all had
      clinical courses consistent with PCP. Twenty-five had negative NIS with PC-DFA
      and were diagnosed as having PCP, by autopsy (n = 2), by a positive
      bronchoalveolar lavage (n = 10), or by having a clinical course consistent with
      PCP (n = 13). Thus, the sensitivity of NIS stained with PC-DFA was 55 percent
      (30/55). This is within the range reported in the literature for induced sputum
      for the diagnosis of PCP. Non-induced sputum stained with PC-DFA can be useful
      for the diagnosis of PCP in HIV-infected patients.

PMID- 9558449
TI  - Mechanism of Hoechst 33342-induced apoptosis in BC3H-1 myocytes.
AB  - Hoechst 33342, a bisbenzimidazole dye, binds to adenine/thymine rich regions in
      the minor groove of deoxyribonucleic acid (DNA). This dye induces apoptosis in
      BC3H-1 myocytes. The mechanism of Hoechst 33342-induced apoptosis was
      investigated. Inhibitors of ribonucleic acid (RNA) synthesis, protein synthesis,
      and serine or cysteine proteases failed to prevent BC3H-1 myocyte death induced
      by Hoechst 33342. Apoptosis may be dependent on increased p53 expression. Hoechst
      33342 had no effect on p53 expression in BC3H-1 myocytes. Lactate oxidation, a
      monitor of mitochondrial function, was altered by Hoechst 33342 in dose dependent
      manner. Also, nuclear extracts were used to assay endogenous topoisomerase I
      activity which was inhibited by Hoechst 33342 treatment of BC3H-1 myocytes.
      Therefore, Hoechst 33342 appears to initiate apoptosis in BC3H-1 myocytes by a
      pathway which is independent of de novo RNA and protein synthesis. However, the
      dye does initiate mitochondrial dysfunction and inhibition of nuclear
      topoisomerase I as two important steps in the apoptotic pathway.

PMID- 9558450
TI  - A laboratorian's view on the College of American Pathologists' Laboratory
      Accreditation Program for Clinical Laboratories.

PMID- 9558451
TI  - By choice or by chance: factors that influenced my life and career.

PMID- 9558452
TI  - The physiological basis of diving to depth: birds and mammals.
AB  - There is wide diversity in the animals that dive to depth and in the distribution
      of their body oxygen stores. A hallmark of animals diving to depth is a
      substantial elevation of muscle myoglobin concentration. In deep divers, more
      than 80% of the oxygen store is in the blood and muscles. How these oxygen stores
      are managed, particularly within muscle, is unclear. The aerobic endurance of
      four species has now been measured. These measurements provide a standard for
      other species in which the limits cannot be measured. Diving to depth requires
      several adaptations to the effects of pressure. In mammals, one adaptation is
      lung collapse at shallow depths, which limits absorption of nitrogen. Blood N2
      levels remain below the threshold for decompression sickness. No such adaptive
      model is known for birds. There appear to be two diving strategies used by
      animals that dive to depth. Seals, for example, seldom rely on anaerobic
      metabolism. Birds, on the other hand, frequently rely on anaerobic metabolism to
      exploit prey-rich depths otherwise unavailable to them.

PMID- 9558453
TI  - Animal adaptations for tolerance and exploitation of poisonous sulfide.
AB  - Many aquatic animal species can survive sulfide exposure to some extent through
      oxidation of the sulfide, which results mainly in thiosulfate. In several
      species, sulfide oxidation is localized in the mitochondria and is accompanied by
      ATP synthesis. In addition, blood-based and intracellular compounds can augment
      sulfide oxidation. The formation of thiosulfate requires oxygen, which results in
      an increase in oxygen consumption of some species. If not all sulfide is
      detoxified, cytochrome C oxidase is inhibited. Under these conditions, a sulfide
      dependent anaerobic energy metabolism commences.

PMID- 9558454
TI  - Biological ice nucleation and ice distribution in cold-hardy ectothermic animals.
AB  - For many ectotherms, overwintering survival depends on the avoidance or
      regulation of ice nucleation and growth within their body fluids. Freeze
      avoidance via supercooling plays an important role in the cold hardiness of many
      small species, particularly terrestrial arthropods, that do not survive the
      freezing of their body fluids. In contrast, mechanisms that limit supercooling
      and initiate freezing at relatively high temperatures promote survival of the few
      invertebrates and vertebrates that tolerate freezing. These mechanisms include
      inoculative freezing, which results from contact with ice in the environment, and
      various ice nucleating proteins, microbes, and crystalloid compounds. In freeze
      tolerant ectotherms, cold hardiness is influenced by complex, seasonally changing
      interactions among physiological factors, ice nucleators, and the physical
      microenvironment. Extraorgan sequestration of ice is a major adaptation of freeze
      tolerance. For most freeze-tolerant species, ice growth is primarily restricted
      to extracellular compartments; however, intracellular freezing also occurs in
      some species.

PMID- 9558455
TI  - The role of vitrification in anhydrobiosis.
AB  - Numerous organisms are capable of surviving more or less complete dehydration. A
      common feature in their biochemistry is that they accumulate large amounts of
      disaccharides, the most common of which are sucrose and trehalose. Over the past
      20 years, we have provided evidence that these sugars stabilize membranes and
      proteins in the dry state, most likely by hydrogen bonding to polar residues in
      the dry macromolecular assemblages. This direct interaction results in
      maintenance of dry proteins and membranes in a physical state similar to that
      seen in the presence of excess water. An alternative viewpoint has been proposed,
      based on the fact that both sucrose and trehalose form glasses in the dry state.
      It has been suggested that glass formation (vitrification) is in itself
      sufficient to stabilize dry biomaterials. In this review we present evidence
      that, although vitrification is indeed required, it is not in itself sufficient.
      Instead, both direct interaction and vitrification are required. Special
      properties have often been claimed for trehalose in this regard. In fact,
      trehalose has been shown by many workers to be remarkably (and sometimes
      uniquely) effective in stabilizing dry or frozen biomolecules, cells, and
      tissues. Others have not observed any such special properties. We review evidence
      here showing that trehalose has a remarkably high glass-transition temperature
      (Tg). It is not anomalous in this regard because it lies at the end of a
      continuum of sugars with increasing Tg. However, it is unusual in that addition
      of small amounts of water does not depress Tg, as in other sugars. Instead, a
      dihydrate crystal of trehalose forms, thereby shielding the remaining glassy
      trehalose from effects of the added water. Thus under less than ideal conditions
      such as high humidity and temperature, trehalose does indeed have special
      properties, which may explain the stability and longevity of anhydrobiotes that
      contain it. Further, it makes this sugar useful in stabilization of biomolecules
      of use in human welfare.

PMID- 9558456
TI  - Routes and mechanism of fluid transport by epithelia.
AB  - The mechanism of fluid transport by leaky epithelia and the route taken by the
      transported fluid are in dispute. A consideration of current mathematical models
      for coupling of solutes and water, as well as the methodologies for the study of
      fluid transport, shows that local osmosis best accounts for water movement.
      Although it seems virtually certain that the tight junctions are water permeable,
      the fraction of absorbed fluid that crosses the tight junction cannot yet be
      determined with confidence.

PMID- 9558457
TI  - Molecular architecture of tight junctions.
AB  - The tight junction creates a regulated barrier in the paracellular pathway and,
      together with the actin-rich adherens junction, forms a functional unit called
      the apical junction complex. A growing number of tight junction-associated
      proteins have been identified, but functions are defined for only a few. The
      intercellular barrier is formed by rows of the transmembrane protein occludin,
      which is bound on the cytoplasmic surface to ZO-1 and ZO-2. These proteins are
      members of the membrane-associated guanylate kinase (MAGUK) protein family and
      are likely to have both structural and signaling roles. Junctional plaque
      proteins without known functions include cingulin, p130, and 7H6; single reports
      describe ZA-1TJ and symplekin. Many cellular signaling pathways affect assembly
      and sealing of junctions. Transducing proteins, which localize within the
      junction, include both heterotrimeric and rho-related GTP-binding proteins, PKC
      zeta and nonreceptor tyrosine kinases. Control of perijunctional actin may be the
      unifying mechanism for regulating paracellular permeability.

PMID- 9558458
TI  - Regulation of the movement of solutes across tight junctions.
AB  - The intercellular tight junction is the rate-limiting barrier in the paracellular
      pathway for permeation by ions and larger solutes. A variety of widely used
      electrical and flux approaches are used in the analyses of solute permeation
      through this pathway; however, each has limitations in practice. It is now clear
      that solute permeation across tight junctions is dynamically regulated by
      intracellular events with a common effector mechanism apparently tied to the
      cytoskeleton. These pathways, which regulate tight junction solute permeability,
      are targets that produce epithelial barrier dysfunction in a variety of disease
      states. However, regulation of solute permeation across the junctional barrier
      may also represent a potential means to improve bioavailability of orally
      administered bioactive solutes.

PMID- 9558459
TI  - Role of tight junctions in establishing and maintaining cell polarity.
AB  - The tight junction (TJ) is not randomly located on the cell membrane, but
      occupies a precise position at the outermost edge of the intercellular space and,
      therefore, is itself considered a polarized structure. This article reviews the
      most common experimental approaches for studying this relationship. We then
      discuss three main topics. (a) The mechanisms of polarization that operate
      regardless of the presence of TJs: We explore a variety of polarization
      mechanisms that operate at stages of the cell cycle in which TJs may be already
      established. (b) TJs and polarity as partners in highly dynamic processes:
      Polarity and TJs are steady state situations that may be drastically changed by a
      variety of signaling events. (c) Polarized distribution of membrane molecules
      that depend on TJs: This refers to molecules (mainly lipids) whose polarized
      distribution, although not the direct result of TJs, depends on these structures
      to maintain such distribution.

PMID- 9558460
TI  - Codependence of renal calcium and sodium transport.
AB  - Calcium and sodium absorption by the kidney normally proceed in parallel.
      However, a number of physiological, pharmacological, pathological, and genetic
      conditions dissociate this relation. In each instance, the dissociation can be
      traced to the distal convoluted tubule, where calcium and sodium transport are
      inversely related. Based on the identification of the relevant sodium
      transporters in these cells and on analysis of the mechanism of calcium
      transport, an explanation for this inverse relation can be developed. Apical
      membrane calcium entry is mediated by voltage-sensitive calcium channels that are
      activated upon membrane hyperpolarization. Basolateral calcium efflux is effected
      primarily by Na+/Ca2+ exchange. According to the model, inhibition of sodium
      entry through either the Na-Cl cotransporter or the Na+ channel hyperpolarizes
      the cell, as does parathyroid hormone, thereby activating the calcium entry
      channel and increasing the driving force for diffusional entry. Membrane
      hyperpolarization also increases the driving force of calcium efflux through the
      Na+/Ca2+ exchanger. Thus sodium-dependent changes of calcium transport are
      indirect and occur secondarily through effects on membrane voltage.

PMID- 9558461
TI  - Aquaporin-2 and -3: representatives of two subgroups of the aquaporin family
      colocalized in the kidney collecting duct.
AB  - Since the molecular identification of the first aquaporin in 1992, the number of
      proteins known to belong to this family has been rapidly increasing. These
      members may be separated into two subgroups based on gene structure, sequence
      homology, and function. Regulation of the water permeability of the collecting
      ducts of the kidney is essential for urinary concentration. Aquaporin-2 and -3,
      which are representative of these subgroups, are colocalized in the collecting
      ducts. Understanding these subgroups will elucidate the differences between
      aquaporin-2 and -3. Aquaporin-2 is a vasopressin-regulated water channel located
      in the apical membrane, and aquaporin-3 is a constitutive water channel located
      in the basolateral membrane. In contrast to aquaporin-3, which appears to be less
      well regulated, many studies have now identified multiple regulational mechanisms
      at the gene, protein, and cell levels for aquaporin-2, thus reflecting its
      physiological importance. Evidence of the participation of aquaporin-2 in the
      pathophysiology of water-balance disorders is accumulating.

PMID- 9558462
TI  - Molecular mechanisms of prostaglandin transport.
AB  - Despite the fact that prostaglandins (PGs) have low intrinsic permeabilities
      across the plasma membrane, they must cross it twice: first upon release from the
      cytosol into the blood, and again upon cellular uptake prior to oxidation. Until
      recently, there were no cloned carriers that transported PGs. PGT is a broadly
      expressed, 12-membrane-spanning domain integral membrane protein. When
      heterologously expressed in HeLa cells or Xenopus oocytes, it catalyzes the
      rapid, specific, and high-affinity uptake of PGE2, PGF2 alpha, PGD2, 8-iso-PGF2
      alpha, and thromboxane B2. Functional studies indicate that PGT transports its
      substrate as the charged anion. The PGT substrate specificity and inhibitor
      profile match remarkably well with earlier in situ studies on the metabolic
      clearance of PGs by rat lung. Because PGT expression is especially high in this
      tissue, it is likely that PGT mediates the membrane step in PG clearance by the
      pulmonary circulation. Evidence is presented that PGT may play additional roles
      in other tissues and that there may be additional PG transporters yet to be
      identified molecularly.

PMID- 9558463
TI  - Organic cation transporters in intestine, kidney, liver, and brain.
AB  - This review focuses on sodium-independent transport systems for organic cations
      in small intestine, liver, kidney, and brain. The roles of P-glycoproteins (MDR)
      and anion transporters (OATP) in organic cation transport are reported, and two
      members of the new transporter family OCT are described. The OCT transporters
      belong to a superfamily that includes multidrug-resistance proteins, facilitative
      diffusion systems, and proton antiporters. They mediate electrogenic transport of
      small organic cations with different molecular structures, independently of
      sodium and proton gradients. The current knowledge of the distribution and
      functional properties of cloned cation transport systems and of cation transport
      measured in intact plasma membranes is used to postulate identical or homologous
      transporters in intestine, liver, kidney, and brain.

PMID- 9558464
TI  - Role of cardiac neural crest cells in cardiovascular development.
AB  - The discovery in the chick embryo that a specific region of the neural crest,
      termed the cardiac neural crest, is essential for septation of the cardiac
      outflow tract and for aortic arch artery development has led to the
      classification of a whole series of human cardiac defects as neural crest
      associated. Recently, several mouse genetic models have been effectively employed
      to yield new insights into the relationship between cardiac neural crest and
      structural heart development. In all the animal models of neural crest-related
      heart defects, prenatal mortality is too high to be attributed to structural
      defects of the heart alone, and there are obvious signs of severe cardiac
      dysfunction. The evidence indicates that poor viability is from impaired cardiac
      excitation-contraction coupling and contractile function at the myocyte level.
      The continued study of experimental and genetically defined models with neural
      crest-associated heart defects will prove useful in identifying the common
      pathways by which the neural crest contributes to normal heart development.

PMID- 9558465
TI  - Molecular insights into cardiac development.
AB  - Recent discoveries have led to a greater appreciation of the diverse mechanisms
      that underlie cardiac morphogenesis. Genetic strategies (primarily gene targeting
      approaches in mice) have significantly broadened research in cardiovascular
      developmental biology by illuminating new pathways involved in heart development
      and by allowing the genetic evaluation of pathways that have previously been
      implicated in these events. Advances have also been made using biochemical and
      cell- and tissue-based approaches. This review summarizes the author's
      interpretation of current trends in the effort to understand the molecular basis
      of cardiac-development, with an emphasis on insights obtained from genetic
      models.

PMID- 9558466
TI  - Normal and abnormal consequences of apoptosis in the human heart.
AB  - Knowledge about apoptosis has become essential for understanding many aspects of
      cardiac structure and function. In the human heart there are major periods of
      morphogenesis that begin only after birth, and some of these processes recur
      intermittently for many years. Although the exact mechanisms by which these
      events are initiated or terminated remain poorly understood, it is clear that
      their benefits may be mirrored in destructive effects. In this review, selected
      examples include normal morphogenesis of the cardiac conduction system and the
      normal postnatal involution of the right ventricle, both of which are mediated by
      apoptosis. Destructive counterparts include familial heart block ending in fatal
      arrhythmias, similar results in the long QT syndrome, and the pathogenesis of
      both Uhl's anomaly and arrhythmogenic right ventricular dysplasia; in each
      apoptosis is an important factor.

PMID- 9558467
TI  - Electrical and calcium signaling in dendrites of hippocampal pyramidal neurons.
AB  - This review discusses recent data regarding the different types of voltage-gated
      Na+, Ca2+, and K+ channels in dendrites of CA1 pyramidal neurons and their
      function for synaptic integration and plasticity. Na+ and Ca2+ channels are
      uniformly distributed throughout the dendrites, although Na+ channels in the soma
      and proximal dendrites differ in their inactivation properties from Na+ channels
      in more distal regions. Also, different regions of the neuron express different
      subtypes of Ca2+ channels. K+ channels are unevenly distributed, with the distal
      dendrites expressing a more than fivefold greater density of a transient A-type
      K+ channel than proximal regions. These K+ channels exert profound control over
      the excitability of the pyramidal neurons and the spread of synaptic potentials
      throughout the dendrites. The ways in which the active properties of dendrites
      may contribute toward the induction and maintenance of long-term synaptic
      plasticity are discussed.

PMID- 9558468
TI  - The synaptic vesicle cycle.
AB  - The ins and outs of the synaptic vesicle cycle are being examined in increasing
      detail with diverse investigative tools in a variety of cell types, particularly
      those with large granules. The cycle begins with the opening of a fusion pore
      that connects the vesicle lumen to the extracellular fluid. Sensitive
      electrophysiological techniques reveal the often-stuttering behavior of single
      pores in non-neuronal cells, through which small molecules trickle until the
      fusion pore expands and the remaining contents erupt from the vesicle. The
      granule membranes are then retrieved by multiple processes that appear to act in
      parallel and that are distinguished from each other kinetically and
      ultrastructurally. Following endocytosis, synaptic vesicles are then shuttled
      back into the vesicle pool, where they briefly mix with other vesicles, become
      immobilized, and remain gelled with their neighbors, even while moving en masse
      again to the presynaptic membrane as a prelude for another round of exocytosis.

PMID- 9558469
TI  - Surfactant proteins: molecular genetics of neonatal pulmonary diseases.
AB  - Genetic and phenotypic complexity has been described for diseases of varied
      etiology. Groups of patients with varied phenotype can be used in association
      studies as an initial approach to identify contributing loci. Although
      association studies have limitations, their value is enhanced by using candidate
      genes with functions related to disease. Surfactant proteins have been studied in
      the etiopathogenesis of neonatal pulmonary diseases. SP-A and SP-B polymorphisms
      are found at a higher frequency in certain groups of patients with respiratory
      distress syndrome (RDS), and SP-B mutations are linked to the pathogenesis of
      congenital alveolar proteinosis (CAP). Phenotypic heterogeneity is observed for
      both CAP and RDS. The available data suggest that a number of factors contribute
      to the etiology of CAP and RDS and, therefore, a multidisciplinary approach of
      clinical, genetic, epidemiologic, and statistical considerations is necessary for
      an in-depth understanding of the pathophysiology of these and other pulmonary
      diseases.

PMID- 9558470
TI  - PreBotzinger complex and pacemaker neurons: hypothesized site and kernel for
      respiratory rhythm generation.
AB  - Identification of the sites and mechanisms underlying the generation of
      respiratory rhythm is of longstanding interest to physiologists and
      neurobiologists. Recently, with the development of novel experimental
      preparations, especially in vitro en bloc and slice preparations of rodent
      brainstem, progress has been made In particular, a site in the ventrolateral
      medulla, the preBotzinger Complex, is hypothesized to contain neuronal circuits
      generating respiratory rhythm. Lesions or disruption of synaptic transmission
      within the preBotzinger Complex, either in vivo or in vitro, can abolish
      respiratory activity. Furthermore, the persistence of respiratory rhythm
      following interference with postsynaptic inhibition and the subsequent discovery
      of neurons with endogenous bursting properties within the preBotzinger Complex
      have led to the hypothesis that rhythmogenesis results from synchronized activity
      of pacemaker or group-pacemaker neurons.

PMID- 9558471
TI  - Sexual differentiation of avian brain and behavior: current views on gonadal
      hormone-dependent and independent mechanisms.
AB  - Gonadal hormones are known to act during development to establish permanent sex
      differences in the anatomy and function of the vertebrate brain. They also act on
      the adult brain to activate reproductive behaviors. However, there are wide gaps
      in our understanding of how sexually dimorphic neural circuits translate into sex
      differences in behavior and other CNS functions. Moreover, not all sexually
      dimorphic properties of the adult brain can be attributed to known effects of
      gonadal hormones during development or adulthood, and factors other than gonadal
      steroids may contribute to these sex differences. This paper reviews sexual
      differentiation and the role of gonadal steroids and non-gonadal factors on
      sexually dimorphic development of the avian brain.

PMID- 9558473
TI  - The luteinizing hormone receptor.
AB  - The luteinizing hormone receptor (LHR) is a member of the subfamily of
      glycoprotein hormone receptors within the superfamily of G protein-coupled
      receptor (GPCR)/seven-transmembrane domain receptors. Over the past eight years,
      major advances have been made in determining the structure and function of the
      LHR and its gene. The hormone-binding domain has been localized to exons 1-7 in
      the extracellular (EC) domain/region of the receptor, which contains several
      leucine-rich repeats. High-affinity binding of LH and human chorionic
      gonadotrophin (hCG) causes secondary hormone or receptor contacts to be
      established with regions of the EC loop/transmembrane module that initiate signal
      transduction. Models of hormone-receptor interaction have been derived from the
      crystal structures of hCG and of the ribonuclease inhibitor, which also contains
      leucine-rich repeats. Such models provide a framework for the interpretation of
      mutational studies and for further experiments. The extracellular domain of the
      receptor has been overexpressed in vitro, which will facilitate crystallographic
      resolution of the structure of the receptor-binding site. The transmembrane
      domain/loop/cytoplasmic module transduces the signal for coupling to G proteins.
      Several constitutive, activating mutations that cause human disease have been
      found in helix VI and adjacent structures. These mutations have provided valuable
      information about mechanisms of signal transfer and G protein coupling. The
      structure of the LHR gene has been elucidated, and the regulation of its
      transcription is beginning to be understood. Valuable insights into receptor
      evolution have been derived from analysis of sequence homologies, the gene
      structure of glycoprotein hormone receptors and other members of the GPCR family,
      and the glycoprotein hormone receptor-like precursors identified in several
      invertebrate species.

PMID- 9558472
TI  - The physiology of parathyroid hormone-related protein: an emerging role as a
      developmental factor.
AB  - Parathyroid hormone-related protein (PTHrP) is the agent responsible for humoral
      hypercalcemia of malignancy. Its pathogenic role in this syndrome is well
      established and attention has focused in recent years on the elucidation of the
      roles played by PTHrP in normal developmental and adult physiology. This review
      focuses on studies of the past two years: (a) elucidation of the
      posttranslational processing pattern of PTHrP, the mechanisms of action of the
      various secretory forms of PTHrP, the role of PTHrP as an intracrine regulator of
      cell growth and cell death; (b) the emergence of PTHrP as a critical
      developmental factor in the mammary gland, epidermis, and the skeleton; and (c)
      the advances in understanding of the roles of PTHrP in the regulation of
      pancreatic islet mass, vascular smooth muscle tone and proliferation, and materno
      fetal calcium transfer across the placenta.

PMID- 9558474
TI  - Sex in the 90s: SRY and the switch to the male pathway.
AB  - In mammals the male sex determination switch is controlled by a single gene on
      the Y chromosome, SRY. SRY encodes a protein with an HMG-like DNA-binding domain,
      which probably acts as a local organizer of chromatin structure. It is believed
      to regulate downstream genes in the sex determination cascade, although no direct
      targets of SRY are clearly known. More genes in the pathway have been isolated
      through mutation approaches in mouse and human. At least three genes, SRY itself,
      SOX9, and DAX1, are dosage sensitive, providing molecular evidence that the sex
      determination step operates at a critical threshold. SRY initiates development of
      a testis from the bipotential cells of the early gonad. The dimorphic male and
      female pathways present a rare opportunity to link a pivotal gene in development
      with morphogenetic mechanisms that operate to pattern an organ and the
      differentiation of its cells. Mechanisms of testis organogenesis triggered
      downstream of SRY include pathways of cell signaling controlling cell
      reorganization, cell proliferation, cell migration, and vascularization.

PMID- 9558475
TI  - Special topic: apoptosis.

PMID- 9558476
TI  - Proteolytic activities that mediate apoptosis.
AB  - Since the discovery that cells can activate their own suicide program,
      investigators have attempted to determine whether the events that are associated
      with this form of cell death are genetically determined. The discovery that the
      ced-3 gene of Caenorhabditis elegans encodes a cysteine protease essential for
      developmentally regulated apoptosis ignited interest in this area of research. As
      a result, we now know that cell death is specified by a number of genes and that
      this biologic process contributes significantly to development, tumorigenesis,
      and autoimmune disease. In this review I summarize what is currently known about
      signaling pathways involved in apoptosis, with particular emphasis on the
      function of the cysteine proteases known as caspases. However, there is also
      evidence that protease-independent cell death pathways exist. Is there a
      relationship between these two distinct mechanisms? If so, how do they
      communicate? Finally, even though the involvement of tumor necrosis factor/nerve
      growth factor family of receptors and cysteine proteases has been elegantly
      established as a component of many apoptotic signaling pathways, what happens
      downstream of these initial events? Why are only a selected group of cellular
      proteins--many nuclear--the targets of these proteases? Are nuclear events
      essential for apoptosis in vivo? Are the cellular genes that encode products
      involved in apoptotic signaling frequent targets of mutation/alteration during
      tumorigenesis? These are only a few questions that may be answered in the next
      ten years.

PMID- 9558477
TI  - The many roles of c-Myc in apoptosis.
AB  - The proto-oncogene c-myc encodes a transcription factor c-Myc, which is of great
      importance in controlling cell growth and vitality. The quantity of c-Myc is
      carefully controlled by many mechanisms, and its actions to induce and repress
      genes are modulated by interactions with other regulatory proteins. Understanding
      the kinetic and quantitative relationships that determine how and what genes c
      Myc regulates is essential to understanding how Myc is involved in apoptosis.
      Reduction of c-myc expression and its inappropriate expression can be associated
      with cellular apoptosis. This review outlines the nature and regulation of the c
      myc gene and of c-Myc and presents the systems and conditions in which Myc
      related apoptotic events occur. Hypotheses of the mechanisms by which expression
      and repression of c-myc lead to apoptosis are discussed.

PMID- 9558478
TI  - Cell cycle regulation and apoptosis.
AB  - Tissue homeostasis requires a balance between cell proliferation and death.
      Apoptosis and proliferation are linked by cell cycle regulators, and apoptotic
      stimuli affect both cell proliferation and death. Glucocorticoids induce G1
      arrest and apoptosis in transformed lymphoid cells. Decreased expression of the
      cell cycle components c-myc and cyclin D3 is essential for glucocorticoid-induced
      growth arrest and death in dividing cells. Other G1 regulators, such as p53, pRb,
      and E2F, have also been implicated in apoptosis. Mice lacking either p53 or E2F
      display aberrant cell proliferation and tumor formation, suggesting that these
      proteins are involved in the elimination of abnormal cells through apoptosis. In
      contrast, pRb induces G1 arrest and suppresses apoptosis in cultured cells. Mice
      that lack pRb are nonviable and show ectopic mitosis and massive cell death,
      suggesting that pRb is an apoptotic suppressor. Further analysis of common
      components of apoptotic and cell cycle machinery may provide insight into the
      coordinated regulation of these antagonistic processes.

PMID- 9558479
TI  - The mitochondrial death/life regulator in apoptosis and necrosis.
AB  - Both physiological cell death (apoptosis) and, in some cases, accidental cell
      death (necrosis) involve a two-step process. At a first level, numerous
      physiological and some pathological stimuli trigger an increase in mitochondrial
      membrane permeability. The mitochondria release apoptogenic factors through the
      outer membrane and dissipate the electrochemical gradient of the inner membrane.
      Mitochondrial permeability transition (PT) involves a dynamic multiprotein
      complex formed in the contact site between the inner and outer mitochondrial
      membranes. The PT complex can function as a sensor for stress and damage, as well
      as for certain signals connected to receptors. Inhibition of PT by
      pharmacological intervention on mitochondrial structures or mitochondrial
      expression of the apoptosis-inhibitory oncoprotein Bcl-2 prevents cell death,
      suggesting that PT is a rate-limiting event of the death process. At a second
      level, the consequences of mitochondrial dysfunction (collapse of the
      mitochondrial inner transmembrane potential, uncoupling of the respiratory chain,
      hyperproduction of superoxide anions, disruption of mitochondrial biogenesis,
      outflow of matrix calcium and glutathione, and release of soluble intermembrane
      proteins) entails a bioenergetic catastrophe culminating in the disruption of
      plasma membrane integrity (necrosis) and/or the activation of specific
      apoptogenic proteases (caspases) by mitochondrial proteins that leak into the
      cytosol (cytochrome c, apoptosis-inducing factor) with secondary endonuclease
      activation (apoptosis). The relative rate of these two processes (bioenergetic
      catastrophe versus protease and endonuclease activation) determines whether a
      cell will undergo primary necrosis or apoptosis. The acquisition of the
      biochemical and ultrastructural features of apoptosis critically relies on the
      liberation of apoptogenic proteases or protease activators from mitochondria. The
      fact that mitochondrial events control cell death has major implications for the
      development of cytoprotective and cytotoxic drugs.

PMID- 9558480
TI  - Regulation of ceramide production and apoptosis.
AB  - Ceramide is a sphingosine-based lipid signaling molecule that regulates cellular
      differentiation, proliferation, and apoptosis. The emerging picture suggests that
      coupling of ceramide to specific signaling cascades is both stimulus and cell
      type specific. Ceramide action is determined within the context of other stimuli
      and by the subcellular topology of its production. Here, we discuss the pathways
      of ceramide generation and the interaction of ceramide with caspases and other
      apoptotic signaling cascades.

PMID- 9558481
TI  - A view of sur/KIR6.X, KATP channels.
AB  - ATP-sensitive potassium channels, termed KATP channels, link the electrical
      activity of cell membranes to cellular metabolism. These channels are
      heteromultimers of sulfonylurea receptor (SUR) and KIR6.X subunits associated
      with a 1:1 stoichiometry as a tetramer (SUR/KIR6.X forms the pores, whereas SUR
      regulates their activity. Changes in [ATP]i and [ADP]i gate the channel. The
      diversity of KATP channels results from the assembly of SUR and KIR6.X subtypes
      KIR6.1-based channels differ from KIR6.2 channels mainly by their smaller unitary
      conductance. SUR1- and SUR2-based channels are distinguished by their
      differential sensitivity to sulfonylureas, whereas SUR2A-based channels are
      distinguished from SUR2B channels by their differential sensitivity to diazoxide.
      Mutations that result in the loss of KATP channels in pancreatic beta-cells have
      been identified in SUR1 and KIR6.2. These mutations lead to familial
      hyperinsulinism. Understanding the mutations in SUR and KIR6.X is allowing
      insight into how these channels respond to nucleotides, sulfonylureas, and
      potassium channel openers, KCOs.

PMID- 9558482
TI  - ClC and CFTR chloride channel gating.
AB  - Chloride channels are widely expressed and play important roles in cell volume
      regulation, transepithelial transport, intracellular pH regulation, and membrane
      excitability. Most chloride channels have yet to be identified at a molecular
      level. The ClC gene family and the cystic fibrosis transmembrane conductance
      regulator (CFTR) are distinct chloride channels expressed in many cell types, and
      mutations in their genes are the cause of several diseases including myotonias,
      cystic fibrosis, and kidney stones. Because of their molecular definition and
      roles in disease, these channels have been studied intensively over the past
      several years. The focus of this review is on recent studies that have provided
      new insights into the mechanisms governing the opening and closing, i.e. gating,
      of the ClC and CFTR chloride channels.

PMID- 9558483
TI  - Functional properties and physiological roles of organic solute channels.
AB  - Membrane channels provide routes for the rapid, passive movement of solutes
      across plasma and intracellular membranes. It is generally assumed that the major
      physiological role of membrane channels is to transport inorganic ions for
      processes such as transepithelial salt absorption and secretion, cell volume
      regulation, signal transduction, and control of membrane electrical properties.
      Increasing evidence indicates, however, that channels play an important role in
      organic solute transport in a wide variety of cell types and organisms. Some of
      the major physiological roles of organic solute channels include uptake of
      nutrients, excretion of metabolic waste products, volume-regulatory organic
      osmolyte transport, and control of mitochondrial metabolism. This article reviews
      the functions and characteristics of channels that participate in the transport
      and regulation of both charged and electroneutral organic solutes.

PMID- 9558484
TI  - Assessment of microsatellite instability in a cell line from a patient with
      xeroderma pigmentosum variant.
AB  - Cells from patients with xeroderma pigmentosum (XP) variant are thought to be
      defective in postreplication repair. This DNA repair pathway is not well defined
      in human cells and the exact genetic defect of XP variant is unknown. In another
      cancer-prone hereditary disorder, hereditary nonpolyposis colon cancer, tumors
      are characterized by a DNA mismatch repair defect with microsatellite
      instability. Since there are some similarities between postreplication repair and
      mismatch repair, we investigated microsatellite instability, the hallmark of a
      DNA mismatch repair defect, in a lymphoblastoid cell line from a patient with XP
      variant. Two normal lines and one nucleotide excision repair-defective XP group A
      line were used as controls. In a host cell microsatellite instability assay, the
      recently developed shuttle vector pZCA29 was transfected into these cells and
      replicated plasmid recovered after 3 days. The plasmid contains two CA repeat
      tracts that interrupt the reading frame of the lacZ gene. Reversion to active
      beta-galactosidase, detectable by a color reaction of bacterial transformants,
      represents the frequency of frameshift mutations in the CA repeat tracts during
      replication of the plasmid, and thereby the host cells' microsatellite
      instability. We did not find any significant differences in the mutation
      frequencies of the plasmids after passage through either cell line. This
      indicates that there is no microsatellite instability in the examined XP variant
      cell line.

PMID- 9558485
TI  - Differential role of catalase and glutathione peroxidase in cultured human
      fibroblasts under exposure of H2O2 or ultraviolet B light.
AB  - The purpose of this study was to elucidate the differential contribution of
      catalase and glutathione peroxidase (GSH-Px) to H2O2 scavenging in cultured human
      dermal fibroblasts. Responses of the cells in terms of both enzyme activities
      were examined by using two sorts of inhibitors, 3-amino-1H-1,2,4-triazole (AT)
      for catalase and DL-buthionine-[S,R]-sulfoximine (BSO) for GSH-Px, under exposure
      to H2O2 or ultraviolet (UV) B radiation. AT treatment resulted in a decrease in
      H2O2 scavenging activity, while BSO treatment did not affect H2O2 scavenging.
      When fibroblasts were exposed to a low concentration of H2O2 (100 microM). AT
      treatment resulted in a significant decrease in cell survival, but BSO treatment
      did not affect survival. At higher concentrations of H2O2 ranging from 500 microM
      to 1 mM, BSO-treated fibroblasts showed reduced survival. In addition, AT
      treatment was much more cytotoxic in the presence of UVB than BSO treatment. The
      intracellular levels of H2O2 in fibroblasts treated with AT or BSO were also
      determined. BSO-treated cells showed similar H2O2 levels to control cells, but
      the intracellular H2O2 levels of AT-treated fibroblasts were 1.4-fold higher than
      found in control cells. These results with human dermal fibroblasts indicate that
      catalase acts as a primary defence against oxidative stress from exogenous or
      endogenous H2O2 at low concentrations. In contrast, GSH-Px helps protect the cell
      from damage during exposure to high concentrations of H2O2.

PMID- 9558486
TI  - Flow cytometric and microscopic characterization of the uptake and distribution
      of phosphorothioate oligonucleotides in human keratinocytes.
AB  - Gene-specific inhibition by antisense oligonucleotides has been successful in a
      large number of systems. In an attempt to use this strategy for the modulation of
      skin disease-specific gene expression, we studied oligonucleotide uptake in
      cultured human keratinocytes. This study revealed a heterogeneous uptake of
      fluorescently labeled phosphorothioate oligonucleotides. Flow cytometric and
      microscopic analysis showed two fluorescent cell populations with differences in
      intensity: a 'bright' population of highly fluorescent small cells and a 'dim'
      population of less fluorescent but larger cells. The heterogeneity in uptake
      between these two populations was not a result of differences in cell cycle
      phases of the keratinocytes, as shown by flow cytometric sorting and measurements
      of relative DNA content. In both populations the oligonucleotides were
      transported intracellularly and were mainly located in the cytoplasm. A typically
      speckled localization pattern was demonstrated by confocal laser scanning
      microscopy. We used propidium iodide (PI) to assess viability, and showed that in
      nonviable (PI-permeable) keratinocytes the oligonucleotides accumulated in the
      nucleus. The use of a lipidfection reagent also changed the intracellular
      distribution of oligonucleotides from a punctate cytoplasmic pattern to an
      intense nuclear localization. The process of uptake by the viable keratinocytes
      was dependent on oligonucleotide concentration, incubation time and temperature.
      This study underlines the importance of kinetic studies on oligonucleotide uptake
      in human keratinocytes which must be considered when specific oligonucleotides
      are used against skin disease-specific genes.

PMID- 9558487
TI  - 5 alpha-reductase activity in the human hair follicle concentrates in the dermal
      papilla.
AB  - Hair growth depends on a close interaction of different cell populations of the
      hair follicle. In certain regions of the body, androgens interfere with this
      highly regulated cooperation in a yet poorly understood manner. The response of
      hair follicles to androgens can be categorized as androgen-dependent, e.g. in the
      beard, androgen-sensitive, e.g. in the frontal scalp of affected individuals, or
      androgen-independent, e.g. in the occipital scalp. At the target cell level, the
      balance between 5 alpha-reductase, 17 beta-hydroxysteroid-dehydrogenase (17 beta
      HSD) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) yields metabolites
      with different androgenic potential. We examined this target cell-specific
      androgen metabolism in microdissected intact sub-units of dermal papillae,
      connective tissue sheaths (CTS) and root sheaths. In dermal papillae, 5 alpha
      reductase predominated with an accumulation of the strong androgen 5 alpha
      dihydrotestosterone. The specific activity of 5 alpha-reductase in the papillae
      exceeded those in the other hair follicle compartments by a factor of at least 14
      in the scalp (5.4, 0.4 and 0.1 pmol/h per mm3 in the papilla, CTS and root
      respectively and at least 80 in the beard (16.0, 0.2 and 0.4 pmol/h per mm3 in
      the papilla, CTS and root respectively). The root sheath keratinocytes expressed
      low 5 alpha-reductase levels, but high 17 beta-HSD levels, with androstenedione
      as the major metabolite. The CTS expressed both 5 alpha-reductase and 17 beta
      HSD, resulting in androstenedione, 5 alpha-androsterone and 5 alpha
      androstanedione. In the CTS and the root sheath, only minor amounts of 5 alpha
      DHT were found. In beard papillae, the 5 alpha-reductase activity was three times
      that in the occipital scalp papillae. These results indicate that the androgen
      response of hair follicles depends on a differentiated intrafollicular androgen
      metabolism and that the dermal papilla might be a primary target in this process.

PMID- 9558488
TI  - Apoptosis in murine hair follicles during catagen regression.
AB  - Catagen hair follicle involution has been reported to involve apoptosis, although
      the precise mechanism has not been satisfactorily resolved. Previous studies have
      involved solely morphological or electron microscopical methods. We report here
      studies on murine hair follicles during the first postnatal hair cycle conducted
      using the terminal deoxy-nucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) method. Electrophoresis of DNA isolated from the hair follicles of the
      same animals was carried out in order to confirm the systematic fragmentation of
      DNA that typifies apoptosis. On day 10, when all the follicles were growing,
      there was no evidence of staining with TUNEL in the hair bulbs. Electrophoresis
      similarly did not show characteristic DNA ladders. By day 15, a few positive
      cells were observed in the hair bulbs and the numbers had increased by day 17
      when many positive cells were seen, especially in the lower portions of the
      follicles. Electrophoresis demonstrated DNA ladders on days 15, 16 and 17,
      although the DNA ladder on day 15 was less prominent than that on day 17. These
      studies confirmed that apoptosis, as identified by techniques that measure DNA
      fragmentation, occurs in the lower regions of hair follicles towards the end of
      catagen.

PMID- 9558489
TI  - Ultraviolet B radiation increases steady-state mRNA levels for cytokines and
      integrins in hairless mouse skin: modulation by topical tretinoin.
AB  - Chronically sun-damaged human skin has a wrinkled, aged appearance as a result of
      alterations in the dermal extracellular matrix. Secondary effectors such as
      cytokines and integrins may mediate the effects of UV radiation on the skin by
      regulating the synthesis of metalloproteinases and structural proteins including
      collagen. The aim of this study was to semi-quantify the steady-state mRNA levels
      of interleukin-1 alpha, tumor necrosis factor alpha, transforming growth factor
      beta, collagenase, stromelysin, collagen, and integrins (alpha, and alpha2) in
      the skin of hairless mice that were either treated with UV or concurrently
      treated with UV and topical tretinoin for 5 weeks. Total RNA was extracted from
      the skin of the mice, reverse transcribed to cDNA, and amplified by the
      polymerase chain reaction in the presence of 32P-dCTP using gene-specific
      primers. Results were normalized relative to glyceraldehyde-3-phosphate
      dehydrogenase levels. Steady-state mRNA levels of the cytokines and integrins
      were increased by UV radiation. Concurrent UV and topical tretinoin treatment
      superinduced the expression of interleukin-1, increased alpha 1, and decreased
      alpha 2 integrin expression. Immunofluorescence analysis showed increased dermal
      localization of beta 1 integrin in UV and tretinoin treated skin. These results
      suggest that cytokines and integrins may be involved in the mechanism of photo
      damage.

PMID- 9558490
TI  - The morphologic changes in lamellar bodies and intercorneocyte lipids after tape
      stripping and occlusion with a water vapor-impermeable membrane.
AB  - It has been reported that artificial restoration of barrier function by a water
      vapor-impermeable membrane after tape stripping induces barrier abrogation in
      hairless mice, impeding rather than enhancing barrier recovery. To address this
      issue, we examined the morphologic changes in the epidermis after tape stripping
      and occlusion with a water vapor-impermeable membrane in murine skin. Male
      hairless mice were used for all studies of barrier perturbation and occlusion.
      Barrier disruption was achieved by repeated application of cellophane tape.
      Immediately after tape stripping the animals were wrapped in a tightly fitting
      water vapor-impermeable membrane. Transepidermal water loss (TEWL) was measured
      20 min after tape stripping and 14, 24, 36, 48 and 60 h after occlusion. For
      electron microscopy the samples were treated with osmium tetroxide (OsO4) or
      ruthenium tetroxide (RuO4). When tape-stripped animals were wrapped in a water
      vapor-impermeable membrane, thereby preventing water flux, barrier function did
      not recover normally. These results demonstrate that an artificial block to TEWL
      with an impermeable membrane did not enhance barrier recovery. By electron
      microscopy many transitional cells and lacunae of various sizes were seen within
      the intercellular spaces of the stratum corneum after occlusion following tape
      stripping. Occlusion also caused alterations in both lipid lamellar membrane
      structures in the stratum corneum interstices and the lamellar bodies in the
      cytosol of granulocytes and transitional cells. Secreted lamellar body contents
      also appeared to be abnormal in the stratum corneum-stratum granulosum junction.

PMID- 9558491
TI  - Quantitative and objective evaluation of wound debriding properties of
      collagenase and fibrinolysin/desoxyribonuclease in a necrotic ulcer animal model.
AB  - Proteolytic enzymes have been used for wound debridement for many years. The two
      enzymes most widely used in Europe are fibrinolysin/desoxyribonuclease and
      collagenase. Despite their frequent use, very few placebo-controlled studies
      comparing the enzymes with vehiculum only, or with each other, are available. In
      a specially developed necrotic ulcer animal model, combined with a computer image
      analysis technique to measure necrotic and total wound surface areas
      quantitatively, we assessed the wound-cleansing properties of fibrinolysin/DNase
      oleogel, collagenase ointment, saline-soaked gauze control treatment, and new
      galenic formulations of collagenase, including placebos. The average relative
      area of necrotic tissue present in the wound after 1 week was 31% for collagenase
      ointment and 56% for fibrinolysin/DNAse oleogel (P = 0.0037). Collagenase gel was
      significantly (P = 0.0007) better in removing necrosis than placebo (gel only).
      Fibrinolysin/DNAse was not significantly more effective than the three placebo or
      control treatments (placebo film, placebo gel, saline-soaked gauzes). We conclude
      that collagenase is a suitable enzyme for wound debridement, but we were not able
      to detect clinical efficacy of fibrinolysin/DNAse in this model.

PMID- 9558492
TI  - Reduced expression of mRNA for transforming growth factor beta (TGF beta) and TGF
      beta receptors I and II and decreased TGF beta binding to the receptors in in
      vitro-aged fibroblasts.
AB  - Previous studies have demonstrated that the expression of type I collagen, the
      most abundant protein in the dermis, is reduced in in vitro-aging fibroblast
      cultures, but the mechanism controlling the reduction of type I collagen
      expression is not understood. Recent studies, however, have demonstrated that
      transforming growth factor beta (TGF beta) plays an important role in the
      regulation of type I collagen expression. The purpose of this study was to
      investigate the role of TGF beta in downregulation of type I collagen expression
      in in vitro-aged fibroblasts. We compared the expression of mRNA for alpha 1 (I)
      collagen, TGF beta, TGF beta type I receptor and TGF beta type II receptor in
      early and late-passage fibroblasts by Northern blot hybridizations. The mRNA
      levels of alpha 1(I) collagen, TGF beta, and TGF beta receptors I and II in late
      passage fibroblasts were reduced to 62%, 62%, 59% and 59%, respectively, of those
      in early-passage fibroblasts. We also compared TGF beta receptor binding in early
      and late-passage fibroblasts using receptor binding assays. The affinity of 125I
      TGF beta in late-passage fibroblasts was lower than that in early-passage
      fibroblasts. These results suggest that the reduction of type I collagen
      expression in in vitro-aged fibroblasts is regulated by reduced expression of TGF
      beta and TGF beta receptors I and II and by decreased TGF beta receptor binding
      ability of the fibroblasts.

PMID- 9558493
TI  - Morphological alterations and cell blebbing in UV-irradiated human epidermis.

PMID- 9558494
TI  - Relationship between keratinocyte proliferative activity, HMB-45 reactivity, and
      the presence of suprabasal melanocytes in acral nevi.

PMID- 9558495
TI  - Inhibitory effects of basic fibroblast growth antisense oligodeoxynucleotide on
      in vitro proliferation of mouse 3T3 fibroblasts.

PMID- 9558496
TI  - Dental unit waterlines: taking the high road ... now.

PMID- 9558497
TI  - Effectively using current sterilization systems.

PMID- 9558498
TI  - Restoration of the aesthetically demanding patient.

PMID- 9558499
TI  - Bleaching tetracycline-stained teeth. A combined approach.

PMID- 9558500
TI  - Specialty endodontics: diagnostic challenges, Part 1.

PMID- 9558501
TI  - Forecasting growth: high-tech breakthroughs open a new era in orthodontics.

PMID- 9558502
TI  - Allergenic materials: a dental office concern. Interview by Phillip Bonner.

PMID- 9558503
TI  - Exploring dental practice growth.

PMID- 9558504
TI  - Computer literacy can save big bucks.

PMID- 9558505
TI  - Hemisection and vital treatment of a fused tooth--literature review and case
      report.
AB  - Fusion and gemination of permanent teeth are developmental anomalies of the
      dental hard tissues which may require endodontic and surgical treatment for
      functional, orthodontic or aesthetic reasons. Following a review of the dental
      literature on tooth fusion and gemination, a case of fusion of a maxillary
      central incisor and a supernumerary tooth and its endodontic and surgical
      treatment is presented.

PMID- 9558506
TI  - Evaluation of technical quality of endodontic treatment--reliability of intraoral
      radiographs.
AB  - The purpose of this study was to evaluate: 1) the use of the conventional
      buccolingual radiographic projection for estimating the technical quality of
      endodontic treatment and 2) the effect of the surrounding tissues on these
      evaluations. The material consisted of three radiographs of each of 108 extracted
      roots: a clinical radiograph, an in vitro radiograph taken in the buccolingual
      projection, and an in vitro radiograph taken in the mesiodistal projection. The
      radiographs were analysed by two observers and consensus was reached and used in
      the analyses. The agreement between the two observers was good, but statistically
      significant differences were found between recordings of the seal in the clinical
      radiographs and the in vitro radiographs taken in the buccolingual projection.
      The length of the root filling in each of the three projections was interpreted
      to be the same, while both inadequate seal and visible lumen apical to the root
      filling were recorded less frequently in the clinical radiographs than in either
      of the two in vitro projections. This difference was most pronounced in molar
      teeth. It was concluded that the lengths of root fillings could be measured
      correctly in clinical radiographs. Due to the anatomy of root canals in incisors
      and canines, there was a risk of misinterpreting an inadequate seal as adequate
      in these teeth. The large amount of tissue surrounding molar teeth tended to
      cause an underregistration of both inadequate seal and lumen apical to the root
      fillings in these regions.

PMID- 9558507
TI  - Comparison of three instruments in the preparation of curved root canals.
AB  - The transportation produced in the apical and middle areas of 30 mesiobuccal root
      canals of human mandibular molars was evaluated after circumferential
      instrumentation using stainless steel K-files (group A), nickel-titanium K-files
      (group B), and clockwise/counterclockwise file rotation using Flexogates (group
      C). The canals were instrumented with files #15 to #35 in size. Apical
      transportation was assessed radiographically while that occurring in the middle
      area was studied microscopically in cross-sections. Although apical
      transportation was greatest in the canals of group A, this difference was not
      statistically significant (P > 0.05). With respect to the middle area of the root
      canal, considerable transportation was observed in 7 of the 30 instrumented
      roots. Of these, five belonged to group A and two to group B, a difference which
      was not statistically significant (P > 0.05). The best results for transportation
      in the middle area of the canal were obtained in group C, in which no
      transportation occurred. This difference was significant when compared with the
      transportation observed in group A (P = 0.02) but not with that in group B (P >
      0.05).

PMID- 9558508
TI  - Survival of avulsed permanent maxillary incisors in children following delayed
      replantation.
AB  - The purpose of this study was to identify the variables that significantly
      influenced the survival of incisors replanted after extended extra-alveolar
      duration at The Hospital for Sick Children, Toronto, Canada, between June 1988
      and December 1993. Survival analysis was used to identify variables that
      significantly influence the retention of replanted incisor teeth. Survival was
      defined as the time that elapsed between the replantation of an avulsed incisor
      and the time it was finally lost. Information on 9 variables was collected for 38
      patients (25 males; 13 females) and 52 replanted permanent maxillary incisors.
      The mean extra-alveolar duration for the sample was 123 min. The mean follow-up
      interval was 942 days (range: 364-2126 days). Incisors replanted with open apices
      had a significantly decreased survival compared with teeth with mature apices (P
      = 0.04; relative risk 4.2). There was also a significant association between
      increased survival and obturation of the root canal with gutta-percha and sealer
      (P = 0.006; relative risk 10.0). A trend towards improved survival of replanted
      incisors was found for children older than 11 years old at the time of
      replantation (P = 0.09; relative risk 2.8). These results are consistent with
      previous studies and may assist clinicians and parents in the decision-making
      process associated with the management of avulsed teeth in children.

PMID- 9558509
TI  - Traumatic dental injuries in a cohort of 16-year-olds in northern Sweden.
AB  - The prevalence and yearly incidence of traumatic tooth injury between 1 and 16
      years of age were studied in a cohort of 16-year-olds, born in 1975, and residing
      in the County of Vasterbotten, northern Sweden. The study comprised 3007 dental
      records from the public dental health service. The general distribution was 50.3%
      girls and 49.7% boys. The records showed that 35% of the children on one or more
      occasions had sustained injury to their primary or permanent dentition. The
      frequency was nearly twice as high for boys (64%) as for girls (36%). Twenty-five
      percent of the 16-year-olds had met with tooth injury more than once and this
      group consisted predominantly of boys. The incidence of injury episodes to
      primary and permanent teeth was 28 per 1000 per year. The boys had sustained
      trauma to their teeth most frequently when they were 4 years of age and between
      the ages of 8 and 11. This was also true for girls at 4 and at 9 years of age,
      although less evidently so. In the primary dentition, the majority of dental
      injuries had affected the supporting tissue of the maxillary incisors. In the
      permanent dentition, 75% of the traumatised teeth were upper incisors. Fractures
      of varying severity constituted 60% of all registered diagnoses in this
      dentition, followed by subluxation (19%) and concussion (11%).

PMID- 9558511
TI  - Childhood obesity: a risk factor for traumatic injuries to anterior teeth.
AB  - The relationship between obesity and traumatic dental injuries was evaluated in a
      study population of 938 6- to 11-year-old schoolchildren from Rome, Italy, and it
      was suggested by the lifestyle and the physical activity of obese children,
      which, according to many authors, is different from the lifestyle of other
      children. The subjects were examined at school: presence and type of dental
      injury, overjet, incisor protrusion, upper lip incompetence and presence of
      obesity were recorded. Trauma predisposition was evaluated with a questionnaire
      investigating the behaviour which may predispose to impacts. Six out of eight
      questions in this questionnaire concerned the children's lifestyle and the trauma
      predisposition score was therefore also considered an estimate of lifestyle and
      physical activity. The dental injury prevalence of the study population was 21.3%
      and obesity prevalence was 11.4%. Of the obese children 30.8% had dental injuries
      vs. only 20.0% of non-obese subjects (P = 0.007). Obese children had only enamel
      and enamel-dentine fractures and the main reported trauma cause was indoor play;
      conversely, lean children also had other types of injuries and the most
      frequently reported cause was outdoor play. The main predisposing factors
      significantly affecting the probability of dental injury, evaluated with multiple
      logistic regression, were upper lip uncoverage (OR: 1.23; P = 0.02), overjet
      larger than 3 mm (OR: 1.68; P = 0.001) and obesity (OR: 1.45; P = 0.01).
      Surprisingly, trauma predisposition was a protective factor (OR: 0.50; P =
      0.00001). The results of this study were explained by the significant inverse
      correlation between obesity and trauma-predisposing behaviour, thus suggesting
      that subjects frequently playing sports and lively games were not only less obese
      but also more skillful and, for this reason, less prone to trauma when they fell
      or sustained impacts.

PMID- 9558510
TI  - Effect of calcium hydroxide dressing on seal of permanent root filling.
AB  - Low apical leakage along root fillings following an application of calcium
      hydroxide was reported in a few methylene blue dye penetration studies. It has
      been found recently that methylene blue is decolored by calcium hydroxide,
      indicating that the short penetration of methylene blue may not be due to a tight
      seal only. Of the 80 roots of human maxillary central incisors used in this
      study, 40 roots (group 1) received calcium hydroxide root canal dressing whereas
      another 40 roots (group 2) did not. All the roots were then obturated with gutta
      percha and Tubli-Seal sealer. Leakage along 20 filled roots in each group was
      measured using a modified fluid transport model at 48 h, 2, 4, 8 and 16 weeks
      after obturation; whereas leakage of another 20 filled roots in each group was
      measured using dye penetration with 1% methylene blue. Using the fluid transport
      model, no significant difference was found between the two groups at any time
      interval (P = 0.4847, 0.3875, 0.9490, 0.4786, 0.9148 respectively after 48 h, 2,
      4, 8 and 16 weeks); using the methylene blue penetration method, leakage in group
      1 (with root canal dressing) was significantly less than that in group 2 (without
      root canal dressing) (P = 0.0374). The contradiction in results from the
      different models indicated that problems existed with the models.

PMID- 9558512
TI  - Apical leakage in canals filled with glass ionomer sealer and gutta-percha after
      dentin conditioning.
AB  - This study assessed in vitro apical leakage in root canals filled with gutta
      percha and Ketac-Endo using different dentin conditioning and filling techniques.
      The root canals of 63 single-rooted teeth were instrumented and randomly divided
      into the following four groups: group A--canals were irrigated with 25% tannic
      acid and filled with Ketac-Endo and a standardized gutta-percha cone; group B-
      canals were irrigated with 1% NaOCl and filled as in group A; group C--canals
      were irrigated with 25% tannic acid and filled with Ketac-Endo and a chloroform
      softened gutta-percha cone adapted to the canal walls; group D--canals were
      irrigated with 1% NaOCl and filled with Grossman's sealer and laterally condensed
      gutta-percha. After storage for 72 hours at 37 degrees C and 100% humidity, the
      gutta-percha was removed to a level 4 mm short of the working length, using a
      Peeso reamer. Teeth were immersed in India ink for 48 hours and cleared, and the
      coronal extent of dye penetration examined under a binocular dissecting
      microscope at x 15 magnification. The mean value of leakage for group A was 0.86
      mm, for group B 2.23 mm, for group C 2.34 mm, and for group D 0.56 mm. Tukey's
      multiple comparison test disclosed significant differences (P < 0.05) between
      group A and groups B and C, and between group D and groups B and C. Differences
      between groups A and D, as well as between groups B and C, were not significant.

PMID- 9558513
TI  - Delayed endodontic and orthodontic treatment of cross-bite occurring after
      luxation injury in permanent incisor teeth.
AB  - A case is presented in which combined endodontic and orthodontic therapy was
      performed in traumatically injured teeth 12 months after an accident. Calcium
      hydroxide treatment was used to halt any possible resorption during orthodontic
      treatment. The teeth were repositioned in a desirable manner without any
      complication by orthodontic treatment. Root canal obturation was accomplished
      after the completion of active orthodontic treatment. Recall examination 12
      months after completion of root canal treatment showed clinical and radiographic
      evidence of healing.

PMID- 9558515
TI  - Are posts mandatory for the restoration of endodontically treated teeth?
AB  - In this era of fiscal and professional accountability, variations in the
      utilization of posts to improve the retention of crowns or other restorations on
      endodontically treated teeth are no longer acceptable. This practice ignores not
      only the potential for root perforations during post space preparations, but also
      the adhesive properties of modern resin-based materials. Since the retention of
      restorations hinges on many other factors, the placement of posts does not
      necessarily assure service quality and may even lead to deleterious changes. The
      need to reappraise the utilization of posts in the restoration of endodontically
      treated teeth cannot be overstated.

PMID- 9558514
TI  - Cyst-like lesion of a developing tooth induced by mandibular fracture.
AB  - A dentigerous cyst-like formation in the lower canine region caused by mandibular
      fracture in a 10-year-old boy is reported. His medical history revealed that he
      had been unconscious for about 2 weeks after traumatic head injuries sustained in
      a traffic accident, and a complicated mandibular fracture had been left untreated
      until his dentist diagnosed the lesion. Eleven months after trauma, a dentigerous
      cyst measuring 20 mm in diameter was found in the fracture area. The lesion was
      enucleated and the boy's postoperative recovery was uneventful. The mass
      completely enveloped the developing canine, and epithelial cells proliferated
      into the connective tissue. However, there was no distinct epithelial lining.
      Small round cell infiltrations and several vessels with thrombosis were noted in
      the cyst wall. The cause of cyst formation was considered to be infection of the
      canine tooth bud and the surrounding soft tissue.

PMID- 9558516
TI  - A quantitative comparison of traditional and non-peroxide bleaching agents.
AB  - Single-rooted premolar teeth, stained with blood utilizing the technique devised
      by Freccia & Peters (1981), were subjected to traditional and non-peroxide
      bleaching agents. Colour changes were recorded over a period of 7 days using a
      Speedmaster R75-CP Reflection Densitometer. The most efficient removal of
      staining occurred after the application of 30% hydrogen peroxide, with sodium
      perborate being 75% as effective. All bleaching agents realized their optimum
      efficacy within the first 3 days. A combination of three enzymes (amylase, lipase
      and trypsin) with disodium edetate was not as effective as the routine bleaching
      agents; however, the combination did have a modifying effect on the blood stains.
      It is suggested that other non-peroxide agents should be investigated to
      determine their efficacy in removing staining from experimentally induced blood
      stained teeth.

PMID- 9558518
TI  - Effect of eugenol on macrophage adhesion in vitro to plastic surfaces.
AB  - This study was performed to investigate the in vitro effect of eugenol on
      substrate adherence capacity of macrophages. Macrophages were obtained from
      Wistar rats. The adherence capacity of macrophages to the plastic surface of
      Eppendorf tubes was determined. Assays were carried out in these tubes for 15 min
      of incubation at 37 degrees C in a humidified atmosphere of 5% CO2 in air.
      Control peritoneal macrophages showed an adherence index = 52.5%. Eugenol
      decreased the adherence index of macrophages in a dose-dependent manner. A 1:1000
      dilution of eugenol decreased the adherence index of macrophages by 16.6% (P <
      0.05). Lower dilutions (1:100 and 1:10) greatly decreased the adherence index by
      51% and 96.2% respectively (P < 0.01). Taking into account that substrate
      adherence is the first step in the phagocytic process of macrophages and in
      antigen presentation, eugenol could inhibit macrophage function and modulate
      immune and inflammatory reactions in dental pulp and periapical tissues.

PMID- 9558517
TI  - Sealing capacity in vitro of thermoplasticized gutta-percha with a solid core
      endodontic filling technique.
AB  - This study assessed the sealing capacity of two endodontic gutta-percha filling
      techniques. Thirty-four single-rooted fully developed teeth were endodontically
      accessed, instrumented and randomly divided into two experimental groups (n = 12)
      and two control groups (n = 5). In Group A, root canals were obturated using a
      solid core thermoplastic technique (Densfil), in Group B and Group C (negative
      control) canals were obturated with laterally condensed gutta-percha, and in
      Group D (positive control) canals were left unobturated. AH-26 was used as the
      sealer. Two days later, the teeth were conventionally prepared for testing apical
      and coronal leakage, immersed in india ink for 5 days and subsequently cleared.
      The linear coronal and apical extent of dye penetration was measured under a
      light dissecting microscope. The mean apical leakage for Group A was 1.39 mm, and
      for Group B 2.76 mm, whereas the mean coronal leakage for Group A was 2.87 mm,
      and for Group B 4.03 mm. The differences between the groups were not
      statistically significant (P > 0.05).

PMID- 9558519
TI  - Prospective study of two retrograde endodontic apical preparations with and
      without the use of CO2 laser.
AB  - This article covers a 4-year study that reports 320 cases in which endodontic
      surgery was performed for residual apical lesions or lesions that could not be
      treated in a conventional way. Four groups of 80 teeth each were formed and they
      were followed up after a 12-month interval. The first group comprised cases
      treated with a micro bur, retrograde filling and IRM; the second, cases treated
      at the apical and radicular portions with a CO2 laser; the third, cases in which
      the retrograde cavity was prepared with an ultrasonic device instead of a micro
      bur; and the fourth group comprised cases treated in a similar way to the second
      group, i.e., cases treated at the apical and radicular portions, but with a CO2
      laser instead of a micro bur. After 12 months, the results showed a better
      prognosis with ultrasonic treatment. Regardless of technique, the CO2 laser did
      not improve the healing process.

PMID- 9558520
TI  - Periodontal ligament vitality and histologic healing of teeth stored for extended
      periods before transplantation.
AB  - A previous study evaluated the viability of dog periodontal ligament cells as
      indicated by tritiated thymidine uptake after extended storage in Hank's balanced
      salt solution and Conditioned Medium. The purpose of this study was to evaluate
      histologic healing following the identical storage parameters established in the
      earlier study. Additionally, for Conditioned Medium, matched pairs (teeth
      evaluated for tritiated thymidine uptake and transplanted teeth) were examined in
      an attempt to correlate periodontal ligament vitality and healing. Forty-six
      extracted endodontically treated dogs' teeth were randomly grouped and stored in
      Hank's balanced salt solution or Conditioned Medium for 6, 48, and 96 h and then
      transplanted into 6-, 48-, and 96-h sockets. The control group teeth were
      transplanted without storage into 6-, 48-, or 96-h sockets. After 6 months the
      dogs were killed and the teeth were prepared for histologic evaluation according
      to Andreasen. Complete healing, inflammatory root resorption, and replacement
      resorption were evaluated and compared. Overall, significantly better healing was
      observed for teeth stored in Conditioned Medium than for teeth stored in Hank's
      balanced salt solution. Conditioned Medium was not significantly different from
      controls. Additionally, there was a positive correlation between periodontal
      ligament viability and healing for Conditioned Medium. These results confirmed
      the importance of periodontal ligament viability in successful replantation and
      the potential of Conditioned Medium as a storage medium for avulsed teeth.

PMID- 9558521
TI  - Oral injury and mouthguard usage by athletes in Japan.
AB  - The use of mouthguards in contact sports effectively prevents oral injury and
      preserves oral structures. We investigated oral injuries and awareness concerning
      mouthguards among Japanese high school soccer and rugby players. Athletes were
      asked a series of questions concerning their history of oral injury while
      participating in sports, and their pattern of mouthguard use was determined. The
      data were evaluated statistically using chi-square analysis. The incidence of
      oral injuries was 32.3% for soccer athletes and 56.5% for rugby athletes, with
      0.8% and 24.1% of the respective groups having mouthguards. There were
      significant differences between the soccer and rugby groups (P < 0.001). Although
      81.8% of soccer athletes thought mouthguards were unnecessary, only 26.2% of
      rugby athletes shared this opinion and there was a significant difference between
      the soccer and rugby groups. Many soccer athletes had insufficient knowledge
      about mouthguards and were not concerned about preventing oral injury, although
      it was in fact a common problem in their sport. Athletes as well as coaches must
      be made aware of the high risk of oral injury when playing soccer, rugby, and
      other contact sports.

PMID- 9558522
TI  - The external and internal anatomy of human mandibular canine teeth with two
      roots.
AB  - This study investigated the internal anatomy of 65 human mandibular canines with
      two well-defined roots. The teeth were decalcified and injected with gelatin
      coloured with india ink. Diaphanization was carried out using clear resin to
      allow permanent preservation. It was found that all mandibular canines with two
      roots had two root canals. Lateral canals were found in 68.9% of teeth and 19.7%
      had lateral canals at the bifurcation. The results of the external measurements
      (cusp tip to root apex) showed that the average buccal root length was 23.0 mm
      and the average lingual root length was 22.7 mm. The maximum and minimum buccal
      lengths were 26.7 mm and 17.9 mm respectively and the maximum and minimum lingual
      lengths were 27.2 mm and 17.1 mm respectively. The buccal root was the larger of
      the two in 47.7% of teeth and 43.1% had roots of equal size. The lingual root was
      larger than the buccal root in 9.2% of cases. Clinicians should be aware of the
      anatomical variation that exists for mandibular canines.

PMID- 9558523
TI  - Transplantation of displaced and dilacerated anterior teeth.
AB  - The therapy of dilacerated permanent anterior teeth usually involves surgically
      removing the tooth. Subsequently, orthodontic methods for closing the space or
      keeping it open are preferred until the patient reaches an age when definitive
      implantological or prosthetic treatments may be used. Anterior tooth
      transplantation should be considered as an alternative to surgically extracting
      the tooth. This study describes a period of investigation covering 3 years during
      which neither replacement resorption nor inflammatory resorption was diagnosed in
      the five transplanted teeth. The clinical tooth mobility was similar to that of
      the adjacent teeth. In spite of the vertical loss of bone shown radiographically
      no pathologically enlarged pockets or recessions have been found. It is not yet
      possible to make any comments on the prognosis for the long term.

PMID- 9558525
TI  - A procedure to raise the tip during correction of the unilateral cleft lip nasal
      deformity.
AB  - A method is reported for the correction of the depressed nasal tip in the cleft
      lip deformities. Open exposure of the nasal frame, septal chondral anterior
      reinsertion, and lipocutaneous composite graft taken from the submastoid or
      retroauricular region and positioned at the basis of the columella are the main
      points of the method. The first results, in 22 patients, are discussed and seem
      promising.

PMID- 9558524
TI  - A case of combined dental development abnormalities: importance of a thorough
      examination.
AB  - This report describes a case of combined dental development abnormalities. A
      patient with a previous ectopically erupted supernumerary maxillary canine
      presented a new ectopically erupted supernumerary premaxillary tooth with dens
      invaginatus (Oehlers' type 2) and an aberrant coronal morphology, including a pit
      in the distal portion of the palatal surface. This tooth would have been
      diagnosed earlier if a panoramic radiograph had been taken at the first visit 5
      months before. This case represents a good example of combined dental development
      abnormalities, i.e., a numerical anomaly (the supernumerary tooth), an alteration
      of dental position (the ectopic eruption), an alteration of dental morphology
      (the aberrant coronal shape), and the invagination. This case highlights the
      importance of a thorough examination, including complementary radiography, of
      patients with a dental anomaly.

PMID- 9558526
TI  - Secondary rhinoplasty: analysis of the deformity and guidelines for management.
AB  - Secondary rhinoplasty aims at modifying the functional and cosmetic defects
      caused by an improperly performed a primary procedure. Correction follows a
      logical sequence from which there is no reason to deviate if one wishes to
      achieve sure results. The sequence includes analysis of the deformity, accurate
      photographic documentation, functional and diagnostic examination, consultation
      with the patient, and precise planning of the different steps of surgery.
      Deformities are grouped in four different sectors depending on the
      characteristics of the repair: upper, intermediate, lower, and inner. However,
      defects may involve more than one sector, making it difficult or impossible to
      establish a precise boundary between them. The surgical technique requires a wide
      exposure of the operating field so that the surgeon can clearly evaluate the
      anatomical deformities and carry out the necessary corrections. For this reason,
      the open approach is the solution of choice. Two types of grafts are commonly
      used in revision rhinoplasty, cartilage and bone. They become necessary to
      reestablish function and to restore volume and/or contour. We strongly believe
      that only autologous grafts can be used. Grafting materials, their sources, and
      applications in different clinical cases are described here.

PMID- 9558527
TI  - Double interdomal suture in nasal tip sculpturing.
AB  - The authors stress that conservative correction should be the main goal in
      rhinoplasty in general and in the surgical treatment of the nasal tip in
      particular. After outlining contemporary concepts and criteria relating to the
      modeling of an aesthetically pleasing nasal tip and the consequent surgical
      planning for its achievement as well as the specific indications for tip plasty,
      they go on discuss the technical aspects of tip projection and rotation. A
      personal technique is proposed for reshaping and sculpturing the tip, completed
      by a double interdomal suture with different application points during closed
      rhinoplasty. The technique also involves ancillary procedures consisting in the
      execution of a series of incisions with a radial pattern at the domal level and,
      when necessary, in the undersurface of the lateral crus. The procedure is
      explained in detail and the results are illustrated and discussed.

PMID- 9558528
TI  - Technical devices in otoplasty to obtain a natural appearance.
AB  - This article outlines the importance given by plastic surgeons to correcting the
      external ear malformations. The objective is to create ears with a normal
      appearance. Despite more than 200 methods proposed by different authors, a
      procedure for otoplasty that gives constant and lasting surgical results has not
      yet been found. Following some critical remarks, both anatomical and surgical,
      the author proposes a method that, in his experience, gives good results, more
      natural and reliable, and is free from failures.

PMID- 9558529
TI  - Refinements in microvascular repair of extended oromaxillofacial defects with
      radial forearm free flap.
AB  - The radial forearm free flap (RFFF) is one of the most widely used and versatile
      fasciocutaneous free flaps in head and neck reconstruction because of its
      qualities--the consistent vascular anatomy; the thin and pliable nature; the
      minimal hair presence; and the possibility of harvesting and transferring it as a
      composite tissue flap, with bone, tendon, and nerve. The RFFF provides a method
      of single-stage reconstruction of wide residual defects after excision of
      advanced cancer (T3-T4) in the head and neck region. We present our ten-year
      experience with RFFF and the good results obtained with some refinements, which
      allowed us to verify the efficacy of the oral competence using the palmaris
      gracilis tendon as a sling. We also present the possibility of harvesting long
      segments of radius (up to 18 cm), and the discovery that use of antithrombotic or
      anticoagulant therapy is not necessary for the flap survival. This treatment does
      not guarantee a complete recovery, but it can improve the quality of the
      patient's life.

PMID- 9558530
TI  - The auriculoparotid region (APR): resection and reconstruction.

PMID- 9558531
TI  - Managed care: effect on future practice.

PMID- 9558532
TI  - Stability of transverse maxillary dental arch dimensions following orthodontic
      surgical correction of anterior open bites.
AB  - A sample of 130 patients with vertical maxillary hyperplasia; mandibular
      hypoplasia with a high mandibular plane angle; narrow, tapered maxillary dental
      arch form; and anterior vertical open bite were collected from three different
      institutions to evaluate the stability of transverse maxillary arch dimensions
      after correction of the open bite. Surgical treatment consisted of Le Fort I or
      bimaxillary osteotomies. Intermolar, interpremolar, and anterior arch widths were
      measured three-dimensionally on dental casts using a Reflex microscope, and
      transverse stability after orthodontic or surgical maxillary expansion was
      analyzed. Orthodontic expansion followed by a one-piece Le Fort I intrusion
      osteotomy was performed in 77 patients, and surgical maxillary expansion by a
      multisegment Le Fort I intrusion osteotomy was performed in 53 patients. The
      increase of transverse arch width and the relapse after orthodontic or surgical
      expansion were not significantly different. The transverse arch width in these
      two groups did not relapse in 20% of the patients after a mean follow-up of 69
      months. An additional bilateral sagittal split osteotomy had no detectable effect
      on stability. Patients who underwent a multisegment Le Fort I osteotomy
      stabilized with rigid internal fixation showed better transverse stability than
      those with intraosseous wire fixation and maxillomandibular fixation. Maxillary
      intermolar and interpremolar arch width relapses were not correlated with tongue
      interposition or loss of interdigitation. The relapse of these arch widths showed
      significant correlations with clockwise rotation of the mandible but not with
      changes of overbite or overjet.

PMID- 9558533
TI  - Effect of presurgical incisor extrusion on stability of anterior open bite
      malocclusion treated with orthognathic surgery.
AB  - The records of 40 nongrowing open bite patients treated with orthodontics and
      maxillary surgery were divided into two groups and evaluated. The extrusion group
      (n = 19) included those patients who had presurgical maxillary incisor extrusion
      of at least 1.5 mm. In the nonextrusion group (n = 21), the maxillary incisors
      were maintained or intruded prior to surgery. Statistical analysis showed no
      relationship between presurgical extrusion of the maxillary incisors and the
      stability of open bite correction; the maxillary incisors were generally stable
      long term in both groups. Overbite decreased a mean of -0.97 mm in the extrusion
      group and -0.67 mm in the nonextrusion group during the mean 5-year 10-month
      follow-up period after appliance removal. Twenty-five percent (10 of 40, 5 from
      each group) of the sample had no incisal overlap long term. These findings
      suggest that a moderate amount of presurgical incisor extrusion or lack of
      extrusion are stable long term and have little influence on posttreatment
      stability of open bites. The decrease in overbite observed after treatment may
      result from the influence of various dental, skeletal, and soft tissue factors
      rather than from any single factor.

PMID- 9558534
TI  - Surgical Class III treatment: long-term stability and patient perceptions of
      treatment outcome.
AB  - To evaluate long-term changes after surgical correction of skeletal Class III
      deformity, postoperative cephalometric radiographs at 1 year and 2 or more years
      postsurgery were digitized for 92 patients who had received either a bilateral
      sagittal split osteotomy for mandibular setback, Le Fort I maxillary advancement,
      or a combination of the two procedures. Patients' perceptions of treatment were
      determined by four self-administered questionnaires: satisfaction, postsurgical
      perception of occlusion and function, problems with facial sensation, and
      postsurgical perceptions. From 1 year to longest follow-up, there were almost no
      mean changes in landmark positions for the maxillary advancement group and
      minimal mean changes in the mandibular setback and two-jaw groups. In all three
      groups, more than 90% of the patients showed no clinically significant long-term
      changes, which suggests that long-term changes are less likely after Class III
      than Class II treatment. At long-term recall, 89% of the patients expressed
      satisfaction with their treatment and would recommend it to others, 74% reported
      improved social interaction, and 63% said their appearance changed as they
      expected. The predominant problems reported were altered facial sensation for 67%
      of the patients and surprise at the length of recovery for 52%.

PMID- 9558535
TI  - Binder syndrome: literature review and long-term follow-up on two cases.
AB  - Binder syndrome has a characteristic clinical appearance including midface
      hypoplasia, flattened nose, convex upper lip, broad philtrum, crescent-shaped
      nostrils, and a deep fold or fossa between nose and upper lip. The incisors may
      be in crossbite with overangulation of the maxillary incisors, and a Class III
      occlusion is common. Radiographic features include small or absent anterior nasal
      spine, thin labial plate over incisor roots, nasomaxillary hypoplasia, and
      skeletal Class III relation. This article reviews the literature in reference to
      Binder syndrome and presents two patients treated by two different techniques
      with long-term follow-up. The first patient was treated with traditional
      orthognathic procedures, whereas the second was treated with a growth-center
      implant to the nose and orthodontics to treat the occlusion.

PMID- 9558536
TI  - Horizontal anchorage in the ascending ramus--a technical note.
AB  - The ascending ramus provides a volume of bone that can receive horizontal screws
      of large sizes in the retromolar area, between the internal and external oblique
      lines. This area is not prone to disuse resorption and the only vital structure
      to consider is the neurovascular bundle. In this article two systems that make
      use of this anatomic opportunity are presented. One is an intraoral distractor,
      used for mandibular lengthening by gradual distraction. The other is a screw
      anchor that provides absolute anchorage for orthodontic tooth movement.

PMID- 9558537
TI  - Health-related quality of life following orthognathic surgery.
AB  - A randomized controlled trial was conducted to compare the effects of rigid and
      wire fixation on health-related quality of life following surgical mandibular
      advancement in patients with Class II malocclusions. Sixty-four patients randomly
      selected to receive rigid fixation with bicortical position screws were compared
      with 63 patients randomly selected to receive nonrigid fixation with inferior
      border wires. Quality of life was measured using the Sickness Impact Profile, a
      generic measure of health-related quality of life, and the Oral Health Status
      Questionnaire, a specific measure of oral health and function designed for use
      with orthognathic surgery patients. Patients were evaluated prior to application
      of orthodontic appliances, approximately 2 weeks before surgery, and 1 week, 8
      weeks, 6 months, 1 year, and 2 years following surgery. Neither instrument
      revealed a statistically significant difference in quality of life between wire
      and rigid fixation at any time period. The health-related disability associated
      with Class II malocclusion is modest compared to many other medical conditions.
      Nonetheless, orthognathic surgery patients exhibit progressive and statistically
      significant improvement in health-related quality of life across a wide variety
      of functional domains, regardless of the fixation method used.

PMID- 9558539
TI  - Paediatric dentistry in Hong Kong.

PMID- 9558538
TI  - A simple classification of orthognathic surgery complications.
AB  - Although orthognathic surgery has now become a routine part of oral and
      maxillofacial surgery practice, the complexity of such surgery together with the
      detailed planning involved makes it a difficult area of surgery to follow in the
      literature. The plethora of literature on the subject of complications in
      orthognathic surgery makes it essential to devise a simple classification of
      complications so that comparative studies can be identified and grouped together
      for more meaningful interpretation. The aim of this article is to present a brief
      and coherent overview of the main complications associated with orthognathic
      surgery for the purpose of establishing a simple classification of complications
      for future reference.

PMID- 9558540
TI  - The management of drooling in children and patients with mental and physical
      disabilities: a literature review.
AB  - Amongst the duties of the paediatric dentist is the provision of oral care to
      patients with the problem of drooling. Many, but certainly not all, of these
      patients have physical and/or learning disabilities. Various methods have been
      advocated for the management of drooling in the paediatric patient and older
      patients with disabilities, including behavioural programmes, biofeedback
      techniques, physiotherapy, biofunctional oral appliances, medication and surgery.
      It is of paramount importance that the patients and/or carers understand the
      advantages and disadvantages of any treatment method being considered. The
      paediatric dentist has an important role to play in explaining the different
      options to the patients and carers, and in implementing some treatment
      modalities, particularly non-surgical approaches. Referral to surgical
      specialists should be seen as 'a last resort' and suggested only if other
      treatment methods have been exhausted. If pharmacological or surgical treatment
      is carried out, careful monitoring for the development of dental caries and other
      problems is essential. The aim of this paper is to provide the paediatric dentist
      with concise overall knowledge of the causes of drooling and treatment options
      available.

PMID- 9558541
TI  - Oral health advice: reported experience of mothers of children aged 5 years and
      under referred for extraction of teeth under general anaesthesia.
AB  - AIMS: To examine the reported receipt of oral health education among mothers of
      children who required the extraction of teeth under general anaesthesia. DESIGN:
      Cross-sectional study using questionnaires completed at interview. SAMPLE: 150
      mothers of children aged 5 or younger who had been referred for extraction of
      teeth under general anaesthesia. SETTING: Dental School, University of Wales
      College of Medicine. RESULTS: 27% of mothers recalled receiving advice from their
      dentist about dental care during their pregnancy. With regard to their child's
      oral health, 48% had received dietary advice and 31% oral hygiene advice from the
      same source. All children lived in areas with suboptimal water fluoride levels;
      27% of mothers had been advised by their dentist to give their child fluoride
      supplements. Few of the mothers recalled receiving advice about oral health from
      their health visitor.

PMID- 9558542
TI  - Dental problems associated with hypophosphataemic vitamin D resistant rickets.
AB  - OBJECTIVE: To review a series of cases of hypophosphataemic vitamin D resistant
      rickets. SUBJECTS INCLUDED: Seventeen cases, aged between 2 years 1 month and 15
      years 9 months at first referral, and with an established diagnosis of vitamin D
      resistant rickets from twelve families were included in the review. Information
      was drawn from patient records for follow-up periods between 9 months and 20
      years 4 months. SETTING: All subjects had been referred to the Eastman Dental
      Hospital between 1973 and 1997. FINDINGS: Abscessed non-carious primary and/or
      permanent teeth were a presenting feature in eleven of the seventeen cases.
      Although attrition and exposure of the abnormally formed dentine accounted for
      the route of infection in primary teeth, the route for microbial invasion of
      pulpal tissues in permanent teeth remained unexplained in a number of patients.
      The possible part played by infractures of the enamel as a portal of entry for
      infection is discussed. Enamel defects were observed in only six patients, in
      three of whom these changes were limited to the primary dentition. Taurodontism
      of permanent molar teeth was confirmed as a feature of the condition in the more
      severely affected male subjects.

PMID- 9558543
TI  - Salivary alterations in insulin-dependent diabetes mellitus.
AB  - OBJECTIVES: To examine the flow rate and composition of unstimulated whole saliva
      and of serum in children with newly diagnosed insulin-dependent diabetes mellitus
      (IDDM) and to compare these with values for a group of healthy controls. DESIGN:
      Cross-sectional. SETTING: Diabetic Department of a University Hospital in
      Thessaloniki, Greece. SUBJECTS AND METHODS: The test group was made up of 10
      recently diagnosed child patients with IDDM, aged 4-15 years and free of other
      systemic disease. Ten healthy children aged 5-17 years served as controls.
      Children were clinically examined before unstimulated saliva was collected over a
      5 minute period and blood samples taken. Saliva and serum measurements included
      glucose, total proteins, albumin and immunoglobulins (IgA, IgG). RESULTS: No
      significant difference was seen in salivary flow rate between the two groups.
      Significantly greater concentrations of glucose were seen in saliva and serum in
      children with IDDM. Neither total protein nor albumin differed significantly
      between the two groups. Salivary IgA concentration was higher in the test group
      as was serum IgG. CONCLUSIONS: Findings in this sample suggest that changes in
      salivary composition may, together with estimated glucose levels, play a helpful
      diagnostic role in the early stages of IDDM in some children.

PMID- 9558544
TI  - Restoration of permanent teeth in young rural children in Cambodia using the
      atraumatic restorative treatment (ART) technique and Fuji II glass ionomer
      cement.
AB  - Several recent studies have demonstrated the success of the ART (atraumatic
      restorative treatment) technique under field conditions in developing countries.
      The ART technique involves removal of caries using only hand instruments, and
      placing a glass ionomer cement (GIC) restoration. OBJECTIVES: To estimate the
      longevity of Fuji II GIC ART restorations placed in permanent teeth by dental
      nurse students under field conditions in rural Cambodia. DESIGN: Clinical field
      trial. SETTING: One high school in rural Cambodia. SAMPLE AND METHODS: 53
      subjects between the ages of 12 and 17 who had dental caries were selected to
      participate. Subjects were randomly assigned to a dental nurse student for cavity
      preparation and placement of ART restorations (without cavity conditioning).
      RESULTS: 92.1% of the carious lesions required class I or class V restorations,
      and 85.4% were in the lower molars. 89 teeth were filled. At 1 and 3 years 86.4%
      and 79.5% of restorations were still present. Restorations were assessed by one
      dentist according to standard criteria. 76.3% of the restorations were judged to
      be successful at 1 year, and 57.9% at 3 years. CONCLUSIONS: Factors which may
      have affected the success rates included: the material used, technical factors,
      failure to condition the cavity prior to restoration, and inexperience of the
      operators. The results suggest that ART restorations in permanent teeth using
      Fuji II GIC are only moderately successful after 3 years. Better results could be
      expected by using a dentine conditioner in conjunction with one of the newer
      stronger glass ionomer cements.

PMID- 9558545
TI  - Root abnormalities, talon cusps, dentes invaginati with reduced alveolar bone
      levels: case report.
AB  - This is a case report of a Caucasian female who presented with an unusual
      combination of dental anomalies: short roots on the maxillary central incisors
      and premolars, talon cusps, dentes invaginati, low alveolar bone heights,
      tubercles of Carabelli on the maxillary first and second permanent molars, with
      pyramidal root morphology in three of the second permanent molars. None of the
      anomalies alone are particularly uncommon but they have not previously been
      reported together. The occurrence of the anomalies is probably incidental as the
      conditions are aetiologically unrelated.

PMID- 9558546
TI  - The dental problems and management of a patient suffering from congenital
      insensitivity to pain.
AB  - Congenital insensitivity to pain is a rare condition usually manifested in
      childhood by a history of unrecognized trauma, indifference to painful stimuli or
      self-mutilation. This paper describes the management of a 13-month-old male who
      had severely lacerated his tongue by habitually chewing it, using soft polyvinyl
      mouthguards retained with a minimal amount of denture fixative.

PMID- 9558547
TI  - A case report of an unusual mandibular swelling in a 4-year-old child possibly
      caused by a jellyfish sting.
AB  - Animal bites and stings may not figure highly in the differential diagnosis of
      facial swelling in the United Kingdom but should be considered in those who have
      been in a tropical area. This case report documents details of the presentation
      and investigation of a case of jellyfish sting that appeared as a facial swelling
      in a 4-year-old girl who had recently been on holiday in Greece. The report
      emphasizes the requirement to consider unusual aetiological factors in cases of
      facial swelling.

PMID- 9558548
TI  - Multiple endocrine neoplasia syndrome type IIb: a case report.
AB  - Multiple endocrine neoplasia type IIb (MEN IIb) is a syndrome, part of which can
      involve neoplastic change in the thyroid and adrenal glands. It has unusual oro
      facial manifestations including mucosal neuromata on the lips, cheeks and tongue.
      A child aged 3 years and 10 months presented with mucosal tags at the corners of
      the mouth, early eruption of permanent teeth, malocclusion and facial asymmetry.
      Biopsy of the excess mucosal tissue suggested a diagnosis of either MEN type IIb
      or neurofibromatosis. Genetic testing eventually confirmed MEN type IIb. The
      patient has been followed up regularly for 9 years. He has developed modular
      lesions on his tongue and irregular enlargement of his lower lip, but to date
      there have been no signs of tumour development. This report emphasizes the
      importance of thorough examination of the oral mucosa and follow-up of any
      abnormalities.

PMID- 9558549
TI  - Dens invaginatus in a primary canine: a case report.
AB  - This article describes an unusual case of dens invaginatus in a primary canine. A
      5-year-old boy presented with an infected mandibular primary canine. A periapical
      radiograph showed a developmental disturbance in the crown diagnosed as dens
      invaginatus. A necrotic pulp has been removed from the tooth and the root canal
      obturated with a resorbable paste. Six weeks later the tooth was found to be
      asymptomatic. A composite restoration replaced the temporary filling material.
      Dens invaginatus may appear in the primary dentition, and early diagnosis is
      important for preventative treatment.

PMID- 9558550
TI  - Implant-supported prosthesis in a child with hereditary mandibular anodontia: the
      use of ball attachments.
AB  - This report describes the provision of an implant-supported hybrid overdenture in
      an 8-year-old child with mandibular anodontia. An interdisciplinary approach to
      treatment planning was employed. Two implant fixtures were placed in the canine
      regions and ball attachments connected to provide support and retention for the
      prosthesis. There was only one implant-related complication during the first
      follow-up year. Close follow-up during the child's growing years is essential for
      the maintenance of the peri-implant tissues and to replace the prosthesis as
      mandibular growth occurs.

PMID- 9558551
TI  - Treatment of avulsed permanent teeth in children. UK National Guidelines in
      Paediatric Dentistry. Royal College of Surgeons, Faculty of Dental Surgery.

PMID- 9558552
TI  - Standards, parameters, and taking care of people.

PMID- 9558553
TI  - Vertical ridge augmentation around dental implants using a membrane technique and
      autogenous bone or allografts in humans.
AB  - This study investigated the effect on vertical bone regeneration of the addition
      of demineralized freeze-dried bone allograft or autogenous bone chips to a
      membrane technique. Twenty partially edentulous patients with vertical jawbone
      deficiencies were selected for this study. The patients were divided into two
      groups of 10 individuals. The 10 patients of Group A received 26 Branemark
      implants in 10 surgical sites. The 10 patients of Group B received 32 implants in
      12 surgical sites. Fifty-two out of 58 implants (22 in Group A and 30 in Group B)
      extended 1.5 to 7.5 mm superior to the bone crest. Titanium-reinforced expanded
      polytetrafluoroethylene membranes were used to cover the implants and, before
      complete membrane fixation, demineralized freeze-dried bone allograft particles
      were condensed under the membrane in Group A, and autogenous bone chips were used
      in Group B. At the reentry after 7 to 11 months the membranes were removed and a
      small biopsy was collected from 11 sites comprehending the miniscrews. The
      clinical measurements from Group A demonstrated a mean vertical bone gain of 3.1
      mm (SD = 0.9 mm, range 1 to 5 mm) with a mean percentage of bone gain of 124% (SD
      = 46.6%). The measurements from Group B showed a mean vertical bone gain of 5.02
      mm (SD = 2.3 mm, range 1 to 8.5 mm) with a mean percentage of bone gain of 95%
      (SD = 26.8%). Histomorphometric analysis of the present study clearly
      demonstrated a direct correlation between the density of the pre-existing bone
      and the density of the regenerated bone. The mean percentage of new bone-titanium
      contact was from 39.1% to 63.2%, depending on the quality of the pre-existing
      bone. Both the clinical and histologic results indicate a beneficial effect of
      the addition of demineralized freeze-dried bone allograft or autogenous bone
      particles to vertical ridge augmentation procedures in humans.

PMID- 9558554
TI  - Guided tissue regeneration using a resorbable membrane in gingival recession-type
      defects: a histologic case report in humans.
AB  - This case report clinically and histologically evaluated the regeneration of
      gingival tissues with the use of resorbable membranes. The study was performed on
      a premolar for which extraction was planned. The exposed root surface was
      thoroughly cleaned and planed with curettes and rotary instruments, and two
      notches were created on the facial aspect of the exposed root surface. A
      resorbable Resolute membrane (WL Gore) was applied above the defect to allow for
      gingival regeneration. After a 6-month healing period, a block section containing
      the root and the regenerated tissues was removed. The biopsy specimen was
      processed to obtain thin ground sections. The histologic analysis demonstrated
      the formation of a newly generated periodontal tissue from the deepest notch
      toward the coronal gingiva. The newly formed tissue was composed of a coronal
      area of connective tissue attachment and an apical area of bone fibers and
      cementum. The present report histologically demonstrates the ability of a
      resorbable membrane to allow complete regeneration of the periodontal ligament in
      the coverage of gingival recessions.

PMID- 9558555
TI  - Implants in regenerated bone: long-term survival.
AB  - This retrospective multicenter study analyzed 526 implants placed and loaded in
      regenerated bone. Both autogenous and allogeneic bone grafts were used in
      combination with a barrier membrane to reconstruct bone using either a
      simultaneous or staged approach. Implants were followed from 6 to more than 74
      months postloading. Eight of the implants were lost, for a success rate of 97.5%.
      The type of graft material did not affect the clinical success of the implants,
      nor did the use of submerged versus nonsubmerged implants or a staged versus a
      simultaneous approach. In conclusion, regenerated bone reacted to implant
      placement in a manner that was clinically similar to native bone.

PMID- 9558556
TI  - Restoration of the severely worn dentition using a systematized approach for a
      predictable prognosis.
AB  - Dental literature supports the concept that vertical dimension of occlusion is
      normally not lost in severely worn dentition, and the bite should generally not
      be opened to facilitate dental reconstruction. However, restoration of a
      periodontally sound but severely worn dentition, at existing vertical dimension,
      frequently presents unique challenges in patient management, diagnosis, treatment
      planning, and restorative methodology. This report reviews and demonstrates an
      integrated and planned approach to this complex treatment situation that can lead
      to a favorable and predictable prognosis. The approach also allows a practitioner
      free use of various techniques if certain goals of occlusion are followed.

PMID- 9558557
TI  - Volumetric changes following barrier regeneration procedures for the surgical
      management of grade II molar furcation defects in baboons: II. Bone, cementum,
      epithelium, and connective tissue.
AB  - In Part I, a computer imaging technique was used to measure the volumetric fill
      that occurred in surgically created grade II molar furcation defects after they
      had been treated using the principles of guided tissue regeneration. In Part II,
      the volumetric fill for each of the specific tissues comprising the defect fill
      (epithelium, connective tissue, bone, and cementum) was compared. The histologic
      material consisted of defects treated using one of three types of surgical
      treatment as well as untreated control sites. All volumetric measurements were
      expressed as a percentage of the original surgically created defect size, with
      100% indicating complete healing of the defect. The results indicate that none of
      the defects achieved complete healing. Teeth receiving flap debridement had the
      most overall defect fill (79.50% comprised of 17.13% bone, 35.81% connective
      tissue, 37.35% epithelium, and 9.71% cementum). Teeth that received a
      biodegradable barrier showed a mean overall defect fill of 74.98% (7.41% bone,
      47.13% connective tissue, 36.20% epithelium, and 9.26% cementum. Sites treated
      with an exclusion barrier showed 70.75% overall fill (9.63% bone, 40.89%
      connective tissue, 39.00% epithelium, and 10.48% cementum). The untreated control
      teeth showed a mean overall fill of 78.70% (5.56% bone, 59.11% connective tissue,
      31.06% epithelium, and 4.27% cementum). No significant differences were found
      among teeth within the same animal and between treatment and controls. The
      following conclusions were drawn: (1) connective tissue comprised nearly one half
      of the total fill of the surgically created defects; (2) the percentage of new
      bone growth was significantly lower than anticipated; and (3) no significant
      differences were found among the treatment modalities and the untreated control
      sites for each of the specific tissue types.

PMID- 9558558
TI  - An integrated approach to optimizing orofacial health, function, and esthetics: a
      5-year retrospective study.
AB  - The restorative dentist treats patients with needs that often transcend dental
      disciplines. This dentist will be responsible for long-term dental maintenance
      and should logically oversee interdisciplinary reconstruction. This case report
      demonstrates an integrated treatment approach and 5-year retrospective study
      involving a patient with maxillary anterior excess, pronounced overjet, and
      advanced periodontitis. Extraction and radical alveolectomy with removable
      prosthesis is often considered in such cases; however, results are often less
      than optimum function, esthetics, and general oral health. In this case, a
      previously undescribed anterior maxillary rotating segmental ostectomy was
      integrated with restorative, periodontal, and removable full and partial denture
      procedures.

PMID- 9558559
TI  - Effect of treatment on cyclosporine- and nifedipine-induced gingival enlargement:
      clinical and histologic results.
AB  - The clinical and histologic responses to periodontal treatment of gingival
      enlargements, induced when cyclosporine and nifedipine were administered singly
      or in combination, were evaluated. A significant correlation was noted between
      plaque, gingivitis, and gingival overgrowth. Severity of enlargement appeared to
      be greater in patients on combined therapy. All treatment approaches such as
      scaling, root planning, gingivectomy, and periodontal flaps, and a combination of
      therapies, were effective in the management of gingival overgrowth up to 1 year
      after completion of treatment. Adjunctive use of chlorhexidine was found to be
      beneficial.

PMID- 9558560
TI  - Biocompatibility of Optibond and XR-Bond adhesive systems in nonhuman primate
      teeth.
AB  - This study evaluated the histologic responses of two different adhesive systems
      on the teeth of seven healthy adult monkeys. Class V cavities in 128 teeth were
      observed at 7,21 to 27, and 90 to 97 days. Statistical data showed no significant
      differences in pulp inflammation between the Optibond (Kerr), XR-Bond (Kerr), and
      IRM (Caulk) groups in pulps at the three time intervals. Some odontoblastic
      disruption and inflammation was seen in pulps restored with XR-Primer at the
      three time intervals. Pulp healing was similar in teeth treated with both direct
      capped Optibond and calcium hydroxide, and there was no significant increase in
      pulpal inflammation with time. No abscesses or necrotic pulps were seen in any
      teeth. Optibond and XR-Bond adhesive systems are biologically acceptable in
      nonhuman primate pulp tissues.

PMID- 9558561
TI  - Sinus pericranii.
AB  - Sinus pericranii is an anomalous extracranial vascular malformation that is in
      continuity with the intracranial dural venous sinuses. Five case reports, three
      congenital and two traumatic, are described. Clinical management, including
      evaluation, diagnosis, and treatment, is discussed. Awareness of this entity by
      plastic surgeons will allow for earlier diagnosis and appropriate surgical
      management, resulting in decreased risk of complications.

PMID- 9558562
TI  - Treatment of craniofacial asymmetry with dynamic orthotic cranioplasty.
AB  - Dynamic Orthotic Cranioplasty (DOC) was developed to treat craniofacial
      deformities associated with positional plagiocephaly. This investigation
      describes the treatment of more than 750 patients with the DOC Band since 1988.
      All patients undergoing DOC treatment were fit with a custom fabricated orthosis
      made from a plaster impression taken from the infant's head. When the orthosis
      was applied, the corrective pressure was directed to hold growth at the calvarial
      prominences and redirect symmetrical growth. A detailed medical history was
      obtained and anthropometric measurements were taken at start, exit, 12, 18, and
      24 months follow-up. This information was recorded in a database created in
      Microsoft Excel. Mean length of treatment was 4.3 months with an average entrance
      age of 6.9 months. Analysis of anthropometric data showed significant reduction
      in mean cranial vault, skull base, and facial asymmetries. Correction of the more
      difficult skull base was documented with computed tomography. Our anthropometric
      and clinical observations document complete or near complete correction of
      asymmetry for a wide variety of head shapes. Based on the results of this
      investigation, we are able to support the earlier claims of our pilot study,
      which concluded that DOC is effective in the treatment of positional
      plagiocephaly.

PMID- 9558563
TI  - Surgical correction of unilateral cleft lip nasal deformity.
AB  - Fifty-five patients with unilateral cleft lip nasal deformities were operated on
      from March 1992 to June 1996. Thirty-one patients were male and 24 were female.
      Three patients were 2 to 5 years of age, 7 patients were 6 to 10 years old, 12
      patients were 11 to 15 years old, 13 were 16 to 20 years old, and 20 were greater
      than 21 years of age. The average follow-up period was 16 months. Combined
      operative procedures, depending on the severity of the cleft lip nasal deformity,
      were the following: (1) a reverse-U incision and Z-plasty for a mild vestibular
      web, (2) a reverse-U incision and V-Y plasty for a moderate vestibular web, (3)
      open rhinoplasty incision combined with a reverse-U incision and V-Y plasty for
      severe flattening or buckling of the cleft lower lateral cartilage, (4) lower
      lateral cartilage suspension or repositioning with or without an onlay cartilage
      graft, (5) alar base advancement, (6) bone graft on the piriform aperture, (7)
      septoplasty and corrective rhinoplasty, and (8) columella lengthening with an
      auricular composite graft. A nasal splint was applied for 3 to 6 months in every
      patient to maintain the corrected nostril contour. Most patients were satisfied
      with their surgical results. We suggest that to achieve a good contour of the
      nose, bony and cartilaginous deformities should be corrected simultaneously with
      correction of the soft tissue.

PMID- 9558564
TI  - Use of scanning electron microscopy in the evaluation of craniosynostosis.
AB  - The cause of craniosynostosis continues to elude researchers. Although several
      studies have looked at the ultrastructure of normal suture closure, no previous
      studies have examined the microarchitecture of the synostotic suture. Our goal
      was to assess the scanning electron microscope (SEM) as a viable and useful tool
      in examining craniosynostosis. Our hypothesis is that the SEM is a powerful
      analytical tool that can evaluate nonsynostotic, partial synostotic, and complete
      synostotic cranial sutures. We analyzed the cranial suture of 3 human infants
      with nonsyndromic sagittal craniosynostosis. The specimens were separated into
      three groups, which included regions of partial and complete synostosis and a
      region of open suture. Histological examination provided cellular and tissue data
      about craniosynostosis, whereas the SEM provided detailed information regarding
      the trabecular microarchitecture of the synostosed suture. The SEM produced
      quality images of complete and partially synostotic sutures and open sutures. At
      low magnification, the SEM characterized the general bony microarchitecture of
      cranial sutures in a manner different from, but complementary to, standard
      histological sections. At higher magnification, the SEM allowed us a look at the
      cellular population of craniosynostotic sutures in a way that surpasses standard
      light microscopy. The SEM is an excellent tool for the study of craniosynostosis
      and has proved invaluable in our ability to evaluate the microarchitecture and
      cellular population of the fusing suture. We believe we have proven our
      hypothesis by demonstrating the SEM to be a powerful analytical tool that can
      evaluate nonsynostotic, partial synostotic, and complete synostotic cranial
      sutures.

PMID- 9558566
TI  - Surgical and implantation reconstruction in a patient with giant-cell central
      reparative granuloma.
AB  - The giant-cell central reparative granuloma, unlike other giant-cell neoplasias,
      is mainly found in maxillary bones, particularly in the mandible. We report a
      patient study of giant-cell central reparative granuloma in the mandible
      extending from dental elements 34 to 44. The patient underwent excision of a
      neoplasm and reconstruction of the mandible via an autologous bone graft of the
      iliac crest. To restore fully, functionally, and aesthetically the masticatory
      apparatus after verification of graft stability, four osseointegrated implants
      were fixed, and an "overdenture" prosthesis was then applied, thus finally
      solving the problem.

PMID- 9558565
TI  - Reasons for removal of rigid internal fixation devices in craniofacial surgery.
AB  - Despite the widespread use of rigid fixation techniques in craniofacial surgery,
      there is a paucity of studies in the literature that serve to better define the
      reasons for the subsequent removal of plates and screws. The current study
      appears to be the first to attempt to assess these issues among a broad range of
      craniofacial surgery patients. Fifty-five patients who underwent hardware removal
      following craniofacial surgery at the University of Michigan Medical Center
      between 1989 and 1995 were retrospectively studied via an in-depth chart review.
      Common reasons for hardware removal included palpable/prominent hardware in 19
      patients (34.5%), loosening of plates and screws in 14 patients (25.5%), pain in
      14 patients (25.5%), infection in 13 patients (23.6%), wound dehiscence/exposure
      of hardware in 11 patients (20%), and removal at the time of secondary procedures
      in 5 patients (9.1%). It is hoped that this study will serve as a tool to define
      more completely the risk of needing subsequent hardware removal among
      craniofacial surgery patients treated with rigid internal fixation.

PMID- 9558567
TI  - Use of microcomputed tomography scanning as a new technique for the evaluation of
      membranous bone.
AB  - Previous basic bone studies in cranial bone biology and bone grafting have used
      calipers, volume displacement, and cephalometric tracings to measure membranous
      bone and to infer fundamental properties of cranial bone. These tools have
      limited accuracy and reproducibility. Histomorphometry has also been used in the
      quantitative analysis of cranial bone; however, two-dimensional histology is
      unable to capture a precise representation of the three-dimensional structure of
      bone. For the first time, we have used the advanced technology of three
      dimensional microcomputed tomographic (micro-CT) scanning as a highly accurate
      and automated tool to precisely measure changes in bone stereology, volume and
      projection, and microarchitecture in the evaluation of membranous bone. The
      advantages of this technology are numerous and include the rapid and
      nondestructive three-dimensional analysis of bone microstructure at resolutions
      between 10 and 75 microns. Measures of "connectivity" in three dimensions and the
      architectural parameter of "anisotropy" are available through micro-CT imaging
      but can only be inferred through two-dimensional histological series. We
      successfully imaged two full-thickness cranial bone specimens and one cancellous
      iliac bone graft. The images demonstrate a similarity between the two membranous
      specimens and a marked difference in comparison with the endochondral graft.
      These differences are borne out by mathematical analysis, and their significance
      is discussed. The utility of micro-CT in the evaluation of membranous bone was
      displayed by its ability to rapidly calculate differences in bone stereology and
      to quantitatively measure morphological changes at an ultrastructural level. We
      believe the benefits of this system will prove to be extremely useful for
      investigations into the basic biology of membranous bone, bone grafts, and
      craniofacial interfaces, and we encourage its use by other scientific
      investigators in the field of craniofacial surgery as they strive for more
      scientifically rigorous tools to understand the basic biology of membranous bone.

PMID- 9558568
TI  - Orbital hemangiopericytoma: case report of a long-term recurrency.
AB  - Among tumors concerning the orbit, hemangiopericytoma is one of the most unusual
      forms. This tumor has a vascular origin and usually appears as a fleshy, well
      circumscribed mass, characterized by slow growth and lack of soreness. Its
      biological traits include a mostly benign nature, a potential malignancy, and,
      most of all, a highly frequent recidivation. This study of double recidivation
      shows this can occur even after a long lapse of time and the new tissue can
      acquire malignant traits. Finally, we describe the modes of the surgical
      approach, which aims at intervening the most radical cases to reduce recidivation
      to a minimum.

PMID- 9558569
TI  - Intracranial migration of microplates versus wires in neonatal pigs after frontal
      advancement.
AB  - Several case reports have demonstrated that microplates migrate intracranially
      when used in the reconstruction of the neonatal craniofacial skeleton. We
      conducted a study to analyze the validity of this finding, to calculate the rate
      of intracranial plate migration, and to compare the migration of microplates to
      standard surgical wire. We hypothesized that, because of constant bone generation
      and resorption in the developing cranial skeleton, both microplates and wires
      would migrate and resorption in the developing cranial skeleton, both microplates
      and wires would migrate intracranially. Bilateral supraorbital osteotomies were
      performed in five 6-week-old Yucatan minipigs. The right side was repaired by
      fixating the bone segment with 32-gauge stainless steel wire. The left side was
      fixed with two microplates (Leibinger Corp, Dallas, TX). The pigs were monitored
      for 6 months. During this time each pig was injected with a fluorescent bone dye
      on the first day of each month. One pig was killed at 3 months and used for
      midpoint comparison. We found that both microplates and wires migrated
      intracranially in these neonatal pigs. None of the plates or wires penetrated the
      dura, but several pieces of hardware from each group migrated far enough to rest
      directly on the dural surface. The rate of plate and wire migration also varied
      slightly among animals, but the mean rate remained relatively constant at 0.91
      mm/month. Computed tomographic scans and morphometric analysis revealed no
      significant difference between the fracture healing and facial growth of the
      microplate and wire sides. We conclude that the biology of bone deposition in the
      calvarium causes any stationary foreign body on the surface of the skull to
      migrate intracranially in the neonate.

PMID- 9558570
TI  - Growing skull fractures: strategies for repair and reconstruction.
AB  - Most skull fractures in growing children heal rapidly and without significant
      contour irregularity. Skull fractures in infants associated with dural injuries,
      however, may progressively enlarge as a result of bone erosion by leptomeningeal
      herniation at the dural tear sites and are known as "growing skull fractures."
      Over a 6-year period, seven growing skull fractures occurred in a population of
      592 consecutive pediatric head injuries at Cardinal Glennon Children's Hospital
      (prevalence, 1.2%). Prompt recognition of growing skull fractures, repair by
      regional craniectomy and pericranial dural inlay graft, and immediate contour
      reconstruction with rigidly fixed cranial bone graft ensure reliable aesthetic
      and functional restoration of the growing neurocranium.

PMID- 9558571
TI  - Growing skull fracture after cranial vault reshaping in infancy.
AB  - Growing skull fractures are reported in three infants undergoing cranial vault
      surgery for craniosynostosis. Although primary dural injury was overt in only one
      patient, an extensive dural defect with spatially coincident bony absence was
      identified in all patients at late exploration. The coincidence of dural injury,
      deficient overlying bone, and a pulsatile growing brain are necessary conditions
      for the development of growing skull fractures. With the advent of increasingly
      radical cranial vault procedures during infancy, the potential for this
      complication to arise may increase. Definitive correction requires autogenous
      tissue reconstruction of the dural and bony defect.

PMID- 9558572
TI  - Use of free composite graft for a large defect in the anterior skull base.
AB  - Until recently, most skull base tumors, particularly those extending into the
      orbit or anterior or middle cranial fossa base, were excised incompletely because
      of the technical difficulty in performing en bloc resections. However, improved
      craniofacial surgical techniques, recent developments in technology and
      equipment, improved imaging techniques, interdisciplinary collaboration, and
      improved anesthetic techniques have enabled a wide range of attempts resulting in
      successful clinical outcome. We present a case of recurrent meningioma with
      intracranial and extracranial extension in which three previous operations left a
      large craniectomy defect in the frontal area as well as a frontal lobe defect.
      After removal of the tumor, we reconstructed the large defect using composite
      graft (free bone and fascia lata).

PMID- 9558573
TI  - McCune-Albright syndrome progressing with severe fibrous dysplasia.
AB  - We present the case of an 11-year-old girl with McCune-Albright syndrome
      associated with severe fibrous dysplasia. In addition to bone lesions, she has
      apparent manifestations of precocious puberty. In examination, a mass at the
      mentum spreading to mandibular corpus bilaterally was seen. This mass has
      affected the mandibular teeth. It was nearly 20 x 20 x 15 cm in size and had
      local necrotic regions on it. The lower lip was expanded too much by the mass.
      Another mass filled the left maxillary sinus, expanding the left zygomatic region
      outwardly and closing the left nasal fossa completely. A rectangular skull shape
      was related to the involvement of cranial bones. After stainless steel, custom
      made mandibular prosthesis was prepared, the patient underwent surgery. A partial
      mandibulectomy was performed, and resulting mandibular bone defect was
      reconstructed by steel prosthesis. Craniofacial involvement occurs in 100% of
      disseminated cases. In the dental literature, mandibular involvement was found in
      20% of cases. However, in studied literature, we did not find a dramatic
      mandibular lesion as severe as that presented here.

PMID- 9558574
TI  - The feet in Pfeiffer's syndrome.
AB  - Broad toes are the classic clinical finding occurring in the feet in Pfeiffer's
      syndrome patients, but few cases undergo formal radiological assessment. However,
      the feet in other craniosynostosis syndromes resulting from mutations of the
      fibroblast growth factor receptor 2 gene have anomalies at many other sites
      within the feet, which raised the possibility that there may also be a wider
      range of anomalies other than broad big toes in the feet of those with Pfeiffer's
      syndrome. The object of this study was to assess prospectively the incidence and
      pattern of clinical and radiographic anomalies of the feet of patients with a
      confirmed diagnosis of Pfeiffer's syndrome. Twenty-two Pfeiffer's syndrome
      patients were examined both clinically and radiologically for anomalies of the
      feet. Clinical examination revealed broad big toes in 12 patients and syndactyly
      in 2. Radiographs of the feet were evaluated by a radiologist with an interest in
      skeletal dysplasia as well as by members of the Craniofacial team. A wider range
      of radiological than clinical anomalies involving the phalanges, metatarsals, and
      tarsals was seen. The severity of the anomalies observed ranged from normal to
      those resembling the feet of Apert's syndrome patients. Only 4 patients had
      radiologically normal feet. These radiographic findings suggest that there is a
      range of foot anomalies more extensive than the broad big toes, which are
      classically associated with Pfeiffer's syndrome.

PMID- 9558575
TI  - Correction of posterior sagittal craniosynostosis.
AB  - Craniosynostosis involving the posterior sagittal suture results in a
      characteristic skull deformity known as bathrocephaly. Surgical correction of
      this deformity using the reverse pi procedure has yielded inconsistent results.
      We present a new method for expanding the transverse posterior skull while
      simultaneously reducing the longitudinal dimension. An absorbable microplate
      reinforced bone strut is used as a framework on which the remainder of the skull
      is reconfigured; its stability prevents relapse. The posterior skull squeeze is
      produced using absorbable mesh plates. Use of rigid fixation is limited to
      absorbable hardware in the growing craniofacial skeleton.

PMID- 9558576
TI  - Apert's syndrome correlates with low fibroblast growth factor receptor activity
      in stenosed cranial sutures.
AB  - Recent genetic studies have shown that Apert's syndrome results from mutations of
      the fibroblast growth factor (FGF) receptor 2 gene. We were interested in
      investigating the expression of FGF receptor 2 at the tissue level in children
      with Apert's syndrome. We studied FGF receptor activity in cranial sutures of
      children with Apert's syndrome and nonsyndromic, isolated craniosynostosis.
      Fourteen children between the ages of 6 months and 12 months were studied. Five
      of these children had Apert's syndrome with coronal suture stenosis. Nine
      children had an isolated, nonsyndromic coronal stenosis. Stenosed and nonstenosed
      cranial sutures were removed at the time of cranioplasty, fixed, decalcified, and
      paraffinized. Immunohistochemistry was performed with labeled, specific anti-FGR
      receptor 2 antibodies. We found lower levels of FGF receptor 2 staining in both
      stenosed and unstenosed sutures of children with Apert's syndrome compared with
      those from children with a nonsyndromic suture stenosis. Furthermore, fused
      sutures from children with Apert's syndrome demonstrated lower levels of FGF
      receptor 2 staining than unfused sutures from the same sample. The findings
      suggest that Apert's syndrome correlates with low FGF receptor 2 activity in
      cranial sutures. These results are consistent with and similar to our findings in
      Crouzon's syndrome, and support genetic studies showing localized mutational
      changes occurring at the FGF receptor 2 gene for both Apert's and Crouzon's
      syndromes. Furthermore, the findings suggest the possibility that variable
      expression of FGF receptor 2 occurs at the tissue level in patients with Apert's
      syndrome.

PMID- 9558577
TI  - Production of human-inducible nitric oxide synthase in radicular cysts.
AB  - To examine if nitric oxide (NO) is produced in radicular cysts, NO synthase (NOS)
      production was analyzed. Periapical tissues were removed from patients at the
      time of endodontic surgery. Frozen tissue sections were histologically evaluated
      with hematoxylin-eosin staining. Production of human-inducible NOS (iNOS) in
      apical cysts was then immunohistochemically examined. Immunoreactive human iNOS
      was widely distributed in epithelial cells, endothelial cells, fibroblasts,
      macrophages, or polymorphonuclear leukocytes. Remarkably, iNOS-positive cells
      were significantly present around blood vessels, and cells residing apart from
      the blood vessels showed weak or no iNOS production, suggesting that only cells
      around blood vessels could be stimulated for iNOS synthesis. These data
      demonstrated the possibility that several, but not all, cells could be stimulated
      to synthesize iNOS in inflamed tissues. In the presence of iNOS, NO can be
      produced spontaneously in periapical lesions and may play a crucial role in the
      regulation of chronic infection.

PMID- 9558578
TI  - Apical leakage of a new glass ionomer root canal sealer.
AB  - A new glass ionomer root canal sealer (Ketac-Endo) has been developed. The
      purpose of this study was to compare the apical leakage of Ketac-Endo and AH26
      using two different filling techniques and a controlled vacuum procedure. Sixty
      four extracted human maxillary anterior teeth were instrumented and divided into
      four groups of 15 roots each. The groups were obturated as follows: group 1, a
      single cone technique and Ketac-Endo; group 2, a lateral condensation technique
      and Ketac-Endo; group 3, a single cone technique and AH26; and group 4, a lateral
      condensation technique and AH26. After storage in 100% humidity at 37 degrees C
      for 1 wk, the root surfaces were coated with two layers of nail polish and sticky
      wax. All specimens were immersed in a vacuum flask containing 2% methylene blue
      dye solution. The air was evacuated with a vacuum pump. The roots were sectioned
      longitudinally, and the linear extent of dye penetration was measured.
      Statistical analysis revealed that there were no significant differences between
      any of the groups.

PMID- 9558579
TI  - Relative distribution of plasma cells expressing immunoglobulin G subclass mRNA
      in human dental periapical lesions using in situ hybridization.
AB  - Immunoglobulin G (IgG)-producing plasma cells are the predominant immunoglobulin
      secreting plasma cells in human dental periapical lesions, compared with
      immunoglobulin A- and immunoglobulin M-producing plasma cells. In this study, the
      cells expressing mRNA, that encoded the distinct IgG subclasses, were detected
      using an in situ hybridization technique in 25 periapical lesions. These lesions
      consisted of 14 periapical granulomas and 11 radicular cysts. Four
      oligonucleotide probes were chemically synthesized from IgG subclass-specific
      hinge region genes to ensure specificity of the probes. Plasma cells expressing
      mRNA, which coded for the IgG subclasses, were detected in formalin
      fixed/paraffin wax-embedded sections. Background staining was negligible in all
      of the sections tested. The in situ hybridization method used in this study was
      both specific and sensitive for the detection of mRNA encoding each of the four
      distinct IgG subclasses, whereas the cells retained good morphology. The relative
      proportions of plasma cells expressing each of the IgG subclass-specific mRNAs in
      both granulomas and cysts were as follows: IgG1 (57.4 and 55.5%); IgG2 (34.1 and
      34.6%); IgG3 (4.0 and 4.3%); and IgG4 (4.0 and 5.5%). There were no significant
      differences between the percentages of plasma cells expressing each of the IgG
      subclass mRNAs between the two types of lesions. IgG1 producing plasma cells
      comprised the highest proportion of IgG-producing plasma cells in both types of
      periapical lesion. IgG2-producing plasma cells were next in abundance, followed
      by plasma cells for either IgG3 or IgG4, which were in roughly equivalent
      numbers.

PMID- 9558580
TI  - Dense-cored vesicles in human dental macrophage-like pulpal cells.
AB  - In the human dental pulp of five healthy premolars, we detected the presence of
      vesicles in the cytoplasm of macrophage-like cells. There were, in general, two
      types of vesicles, with regard to their size and content. The first was of
      smaller size (35 to 55 nm), and they were electron optically empty. The second
      type included larger vesicles (100 to 150 nm) presenting a heavily and
      homogeneously osmiophilic dense core. Their overall morphology was strikingly
      similar to the well-known, dense-cored vesicles of the sympathetic and
      neuroendocrine systems. This morphological evidence may be considered as an
      adjunctive support for the neural crest derivation of the dental pulp.

PMID- 9558581
TI  - Transformation and preliminary characterization of primary human pulp cells.
AB  - The odontoblast is the cell responsible for dentin formation and mineralization
      during tooth development. A number of primary pulp cell culture systems have been
      used to study the mechanism of dentinogenesis in vitro. One of the difficulties
      in using primary cells is the limited number of cell divisions they will undergo.
      In this study, this problem was addressed by transfecting primary cultures of
      human pulp cells with an SV40-adenovirus construct. This resulted in the
      establishment of transformed human pulp cells, which were named HPC-T. A series
      of preliminary experiments were performed to characterize these cells, including
      their morphology, cell proliferation, alkaline phosphatase production, and
      cytogenetic make-up. The results demonstrate that SV40-transformed human pulp
      cells retain many of the characteristics of the parent primary cells and may be
      useful in the study of pulp cell function in vitro.

PMID- 9558582
TI  - Bacterial leakage of mineral trioxide aggregate as compared with zinc-free
      amalgam, intermediate restorative material, and Super-EBA as a root-end filling
      material.
AB  - Several dye leakage studies have demonstrated the fact that mineral trioxide
      aggregate (MTA) leaks significantly less than other root-end filling materials.
      The purpose of this study was to determine the time needed for Serratia
      marcescens to penetrate a 3 mm thickness of zinc-free amalgam, Intermediate
      Restorative Material (IRM), Super-EBA, and MTA when these materials were used as
      root-end filling materials. Fifty-six, single-rooted extracted human teeth were
      cleaned and shaped with a series of .04 Taper rotary instruments (Pro-series 29
      files). Once the canals were prepared in a crown down approach, the ends were
      resected and 48 root-end cavities were ultrasonically prepared to a 3 mm depth.
      The teeth were then steam sterilized. Using an aseptic technique, under a laminar
      air flow hood, the root-end cavities were filled with amalgam, IRM, Super-EBA,
      and MTA. Four root-end cavities were filled with thermoplasticized gutta-percha
      without a root canal sealer and served as positive controls. Another four root
      end cavities were filled with sticky wax covered with two layers of nail polish
      and served as negative controls. The teeth were attached to presterilized
      (ethylene oxide gas) plastic caps, and the root ends were placed into 12-ml vials
      of phenol red broth. Using a micropipette, a tenth of a milliliter of S.
      marcescens was placed into the root canal of each tooth. To test the sterility of
      the apparatus set-up, the root canals of two teeth with test root-end filling
      materials and one tooth from the positive and negative control groups were filled
      with sterile saline. The number of days required for S. marcescens to penetrate
      the four root-end filling materials and grow in the phenol red broth was recorded
      and analyzed. Most of the samples filled with zinc-free amalgam leaked bacteria
      in 10 to 63 days. IRM began leaking 28 to 91 days. Super-EBA began leaking 42 to
      101 days. MTA did not begin leaking until day 49. At the end of the study, four
      of the MTA samples had not exhibited any leakage. Statistical analysis of the
      data indicated Mineral Trioxide Aggregate to be a most effective root-end filling
      material against penetration of S. marcescens.

PMID- 9558583
TI  - Apical extrusion of debris using two hand and two rotary instrumentation
      techniques.
AB  - The purpose of this study was to investigate the quantity of apical debris
      produced in vitro using two hand and two rotary instrumentation techniques. Sixty
      minimally curved, mature human mandibular premolars with single canals were
      divided into 4 groups of 15 teeth each and prepared using step-back
      instrumentation with K-files, balanced force with Flex-R files, Lightspeed nickel
      titanium instruments, or .04 taper ProFile Series 29 rotary nickel-titanium
      files. Debris extruded through the apical foramen during instrumentation was
      collected on preweighed filters. The mean weight of extruded debris for each
      group was statistically analyzed using a Kruskal Wallis one-way analysis of
      variance and a Mann-Whitney U rank sum tested. Although all instrumentation
      techniques produced apically extruded debris, step-back instrumentation produced
      significantly more debris than the other methods (p < 0.0001). There was no
      difference between balanced force hand instrumentation and the two rotary nickel
      titanium instrumentation methods (p > 0.05). Hand or engine-driven
      instrumentation that uses rotation seems to reduce significantly the amount of
      debris extruded apically when compared with a push-pull (filing) technique.
      Decreased apical extrusion of debris has strong implications for a decreased
      incidence of postoperative inflammation and pain.

PMID- 9558584
TI  - Perforation repair comparing mineral trioxide aggregate and amalgam using an
      anaerobic bacterial leakage model.
AB  - The purpose of this study was to evaluate the ability of mineral trioxide
      aggregate (MTA) and amalgam to seal furcal perforations in extracted human molars
      using an anaerobic bacterial leakage model. Furcal perforations were made in 39
      maxillary and mandibular human molars with a high-speed bur. These were randomly
      divided into two experimental groups of 18, with the remaining three teeth used
      as positive controls. Experimental group 1 was repaired with MTA and group 2 with
      amalgam. Three additional teeth without perforations served as negative controls.
      A dual chamber anaerobic bacterial leakage model was assembled. Brain heart
      infusion broth with yeast extract, hemin, menadione, and the chromogenic
      indicator bromcresol purple was used as the culture broth for Fusobacterium
      nucleatum. Eight of 18 amalgam samples leaked, whereas none of the 18 MTA samples
      leaked. MTA was significantly better than amalgam in preventing leakage of F.
      nucleatum past furcal perforation repairs.

PMID- 9558585
TI  - A histopathological study of the effects of low-power laser irradiation on wound
      healing of exposed dental pulp tissues in dogs, with special reference to lectins
      and collagens.
AB  - This study investigated the effects of low-power laser irradiation on exposed
      pulp tissue in dogs. Gallium-aluminium-arsenide diode laser (300 mW) irradiation
      was applied to the exposed surface of the pulp, and histopathological changes
      were observed at 1, 3, and 7 wk after the operation. In addition, the lectin
      (concanavalin A, Dolichos biflorus agglutinin, peanut agglutinin, Ricinus
      communis agglutinin I, soybean agglutinin, Ulex europeus agglutinin I, and wheat
      germ agglutinin) binding pattern and distribution of collagens (type I, III, and
      V) were examined to determine the histochemical and immunohistochemical nature of
      wound healing. The fibrous matrix formation and the continuing changes in the
      dentin bridge formation of the irradiation group were observed earlier (1 wk
      after the operation) than in the nonirradiation control group. Lectin
      histochemistry and collagen immunohistochemistry showed that concanavalin A,
      peanut agglutinin, wheat germ agglutinin, and collagens (types I, III, and V)
      were distributed in the fibrous matrix and dentin bridge. The expression of these
      lectins and collagens occurred earlier in the laser irradiation group than in the
      control group. These results suggest that laser irradiation accelerates wound
      healing of the pulp and the expression of the lectins and collagens. Furthermore,
      D-glucose-, D-mannose-, N-acetyl-D-galactosamine-, and N-acetyl-neuraminic acid
      binding sugars and type I, III, and V collagens play an important role in the
      healing of pulp wounds.

PMID- 9558586
TI  - Histopathological evaluation of the tissue reactions to Endo-Fill root canal
      sealant and filling material in rats.
AB  - In this in vivo study, the tissue reactions to silicone-based Endo-Fill root
      canal filling material were histopathologically evaluated. The reaction of rat
      connective tissue to polyethylene tube implants that were filled with Endo-Fill
      were evaluated at 2 days, at 1, 2, 4, and 8 weeks. Four tube were implanted in
      each rat subcutaneously, and a total of 15 rats were used. Rats were killed, and
      the specimens were examined under the light microscope (x115 and x230). At the
      end of 8 wk, a thin fibrous wall with an almost completed advanced healing
      process was observed around the implant material, but no capsule formation or any
      inflammatory infiltration was seen.

PMID- 9558587
TI  - Dowel space preparation in root canals filled with glass ionomer cement.
AB  - The aim of this study was to evaluate post space preparation difficulties in
      canals filled with Ketac Endo and with Grossman's sealer. Sixty-three single
      rooted teeth were prepared using a step-back technique and were divided into four
      groups: group 1--canals were irrigated with 25% tannic acid and filled with Ketac
      Endo and a single-cone technique; group 2--canals were irrigated with 1% sodium
      hypochlorite and fillings done as in the previous group; group 3--canals were
      irrigated with 25% tannic acid and filled with Ketac Endo and one gutta-percha
      cone previously adapted with chloroform; and group 4--canals were irrigated with
      1% sodium hypochlorite and filled with Grossman's sealer and a lateral
      condensation technique. After 72 h, canals post space were prepared using Peeso
      drills. The time required was measured in seconds and analyzed by Tukey multiple
      comparison test (level 5%). Post space preparation time for groups 1 to 3 was
      longer than for group 4 and longer for group 1 than for groups 2 to 4.

PMID- 9558588
TI  - Demonstration of a possible source of error with an electric pulp tester.
AB  - The purpose of this study was to determine whether electrical current can travel
      between adjacent teeth through contacting interproximal amalgam restorations.
      Twenty-two extracted human premolars were restored with class II amalgam
      restorations. They were then mounted in pairs in self-curing resin, simulating
      adjacent teeth. Only their restorations were allowed to contact. An electrical
      multimeter was used to supply electrical current and to measure any current
      passing through the mounted teeth. One current measurement was made from the
      buccal enamel of a tooth to the occlusal surface of the filling in that tooth. A
      second measurement was made from the buccal enamel of the same tooth to the
      occlusal surface of the adjacent filling. These two measurements were made for
      all 11 trials. Statistically, all current that entered the first tooth passed to
      the adjacent tooth. This finding suggests a potential source of error when using
      an electric pulp tester.

PMID- 9558589
TI  - Topical anesthetic as an adjunct to local anesthesia during pulpectomies.
AB  - A technique is described using topical anesthetic to supplement local anesthesia.
      It is the author's opinion that it enhances patient comfort during pulpectomies
      on teeth with irreversible pulpitis.

PMID- 9558591
TI  - Bleaching teeth: report of a survey, 1997.
AB  - Vital tooth bleaching is here--it is a viable, predictable concept providing
      great patient acceptance and satisfaction. Practitioners are advised to educate
      patients routinely about bleaching and to upgrade themselves and their auxiliary
      staff to be able to accomplish all aspects of bleaching.

PMID- 9558590
TI  - Two-stage pontic retainer fabrication: a case report of a new technique for an
      immediate provisional bridge.

PMID- 9558592
TI  - Esthetic correction for teeth with fluorosis and fluorosis-like enamel
      dysmineralization.

PMID- 9558593
TI  - Surgical tooth lengthening: biologic variables and esthetic concerns.

PMID- 9558594
TI  - Case report: in-office tooth whitening procedure with 35% carbamide peroxide
      evaluated by the Minolta CR-321 Chroma Meter.

PMID- 9558595
TI  - Chewing tobacco and cancer: a growing threat.

PMID- 9558596
TI  - Chewing tobacco and oral cancer: Part Two.

PMID- 9558597
TI  - Spit tobacco: not a safe alternative.
AB  - Contrary to popular belief spread by misleading advertisements, spit tobacco is
      not a safe alternative to cigarettes. An abundance of evidence indicates that
      these products are not only dangerous to health, but often lethal. In Michigan, a
      statewide educational campaign is now underway to alert the public to the facts
      about spit tobacco. The National Institute of Health recommends that dentists ask
      all patients, beginning at age 5, about their tobacco use. The use of nationally
      known celebrities seems a critically important ingredient in this anti-tobacco
      campaign, in order to offset the glamorous advertisements from the tobacco
      industry. Ultimately, however, it is steady, sure, ever-serious reminders by
      health professionals of the dangers of spit tobacco that will carry the most
      weight. Above all, it is the dentist who has this opportunity and this
      responsibility.

PMID- 9558598
TI  - The crash of Comair flight 3272.

PMID- 9558599
TI  - Lack of communication limits your dental practice.

PMID- 9558600
TI  - Washtenaw Community College's Alternative Dental Assistant Education Project.

PMID- 9558601
TI  - [Bacteremia: a Spanish multicenter study with 5000 cases. The Hospital Infection
      Study Group (GEIH)].
AB  - INTRODUCTION: Bacteremia is one of the most common nosocomial infections and is
      still a severe condition that frequently represents a life-threatening problem
      for the patient. MATERIAL AND METHODS: SEPSIS DATA is a software programme
      developed by the SEIMC (Spanish Society of Infectious Diseases and Clinical
      Microbiology) nosocomial infection study group, and it has been designed to
      collect under common criteria bacteremia cases from Spanish hospitals. In this
      study, we analyse the results from the first 5,000 cases prospectively collected
      from 34 hospitals with the following distribution by number of beds: 8 hospitals
      with less than 200, 15 between 200 and 499.6 between 500 and 999 and 5 with more
      than 1,000 beds. RESULTS: Male patients (60%), older than 61 years (52%) are the
      predominant group. Bacteremia acquisition was extra-hospital in 58% of the cases.
      Most frequent underlying disease was neoplasm (22%) and 9% of the patients had
      HIV infection. Most frequent bacteremia sources were urinary tract (19.6%),
      primary (16%) and respiratory tract (15%). Most commonly isolated micro-organisms
      were E. coli (23%). S. aureus (13%), coagulase-negative Staphylococci (12%) and
      S. pneumoniae (8%). Microorganisms average time to grow in laboratory was 1.95
      days. Origin focus of bacteremia was reported in 30% of the cases. Antibiotic
      therapy used was active against pathogen isolate in 96% of the cases. Adequate
      treatment was started empirically from the first day in 76% of the cases. Third
      generation cephalosporines were the antibiotic group most used (28%). Among the
      observed complications, 7.68% of the episodes occurred with shock and 2.68% with
      septic metastasis. Crude mortality until the end of episode was 16.64%.

PMID- 9558602
TI  - [Community-acquired bacteremias].

PMID- 9558603
TI  - [Hospital-acquired bacteremias].

PMID- 9558604
TI  - [Bacteremias of urinary origin in patients with a bladder catheter].

PMID- 9558605
TI  - [Community-acquired bacteremias of respiratory origin].

PMID- 9558606
TI  - [Hospital-acquired bacteremias of respiratory origin].

PMID- 9558607
TI  - [Bacteremias of gastrointestinal origin].

PMID- 9558608
TI  - [Catheter-associated bacteremia].

PMID- 9558610
TI  - [Bacteremia in bronchopathy patients].

PMID- 9558609
TI  - [Primary bacteremia].

PMID- 9558611
TI  - [Bacteremia in patients with tumor diseases. The Hospital Infection Study Group
      (GEIH)].

PMID- 9558612
TI  - [Bacteremia in HIV-infected and IVDA patients].

PMID- 9558613
TI  - [Nosocomial bacterial infection. Spanish reality in the '90-s].

PMID- 9558614
TI  - [Treatment and course of meningitis caused by penicillin-resistant pneumococcus].

PMID- 9558615
TI  - [Nosocomial pneumonia. Etiologic spectrum, diagnostic methods and treatment].

PMID- 9558616
TI  - [New concepts of sepsis and septic syndrome. Etiologic correlations].

PMID- 9558617
TI  - [Infectious arthritis: current etiologic profile].

PMID- 9558618
TI  - [Severe infections of the skin and soft tissues].

PMID- 9558619
TI  - [Spontaneous bacterial peritonitis in liver cirrhosis. Physiopathology, treatment
      and prevention].

PMID- 9558620
TI  - [New bacteria causing infectious diseases].

PMID- 9558621
TI  - [Cefotaxime: current status and future prospectives after 15 years of
      experience].

PMID- 9558622
TI  - Methods in dental public health research and practice: a new feature for the
      JPHD.

PMID- 9558623
TI  - Establishing maternal and child health data collection priorities for state and
      local oral health programs.
AB  - OBJECTIVE: This paper identifies specific data items for use by state and local
      agencies in a maternal and child oral health needs assessment model. METHODS: A
      modified Delphi approach was used to develop consensus on items for inclusion in
      the data set and their relative importance. Initially, 31 data items were chosen
      from several national sources. All state dental directors, along with other
      selected administrators and advisory committee members for this process, were
      asked to categorize each of the data items as core (essential), important but
      optional, or of lesser importance. Short comments about each data item were
      accepted, as were additions to the list of data items. Two rounds of comments
      were held. RESULTS: Eleven data items/types of information were selected as core
      items to be included in all needs assessments. All but one of these items were
      determined by the scores of the respondents. The advisory committee strongly
      recommended that at least one core item relate to the public's perception of oral
      health. Some differences in perceived importance of several items existed among
      the state dental directors, local dental directors, and the advisory committee.
      Twenty-one items were identified as being important, but optional, and seven were
      considered less than important and not included in the model data set.
      CONCLUSIONS: A modified Delphi approach facilitated the development of core and
      optional data items for a model oral health needs assessment. This model has
      potential for a common reporting mechanism so that states and local dental
      programs can share data.

PMID- 9558624
TI  - Validity of two methods for assessing oral health status of populations.
AB  - OBJECTIVE: This investigation assessed two methods for estimating epidemiologic
      indicators of oral health status among children: (1) a visual-only screening,
      performed independently by a dental hygienist and a registered nurse; and (2) a
      parent- or guardian-completed questionnaire. The indicators included dichotomous
      variables measuring dental caries and treatment needs, presence of sealants,
      injuries to the anterior teeth, and dental fluorosis. METHODS: Following training
      and calibration, data were collected over an eight-day period in April 1994 among
      632 elementary schoolchildren (aged 5 to 12 years) in Monticello, Georgia. Both
      screening and questionnaire findings were compared pairwise with results from
      visual-tactile examinations done by a dentist. Validity, represented by
      sensitivity, specificity, and predictive values, was assessed for screening
      results from the dental hygienist, the nurse, and the parent-completed
      questionnaire. RESULTS: Validity was high for screening for caries and treatment
      needs (> 90% for sensitivity, specificity, and predictive values in a sample
      having 30% to 40% prevalence). Less valid data--mainly an effect of false
      negatives--were obtained for fluorosis, injuries, and presence of sealants. No
      significant difference in validity was observed between the nurse and the dental
      hygienist. One-third of respondents to the questionnaire did not know if their
      children needed fillings (a proxy for untreated decay) or had received sealants;
      only knowledge of restorations was comparable to results from screening.
      Intraexaminer reliability for the two screeners ranged from 85 to 100 for percent
      agreement and 0.70 to 0.93 for kappa scores. CONCLUSIONS: Screening by dental
      hygienists or nurses can provide valid data for surveillance of dental caries and
      treatment needs. Training for visual assessment of fluorosis and injuries must be
      improved to diminish the proportion of false negatives. A parent-completed
      questionnaire is less effective than visual screening for evaluating oral health
      status in children.

PMID- 9558625
TI  - Measuring beliefs about orthodontic treatment: a questionnaire approach.
AB  - OBJECTIVES: Few studies have examined what parents and orthodontists expect from
      and value about orthodontic treatment. In this study, we designed and tested a
      questionnaire to outline what drives consumer demand for children's orthodontic
      care. Further, we present data from the questionnaire to illustrate how
      expectations and values pertaining to orthodontic treatment relate to
      sociodemographic variables. METHODS: Subjects were 220 Pennsylvania orthodontists
      and 220 parents at a university orthodontic clinic who were administered a
      questionnaire designed to assess what parents and orthodontists value about and
      expect from orthodontic treatment. Items for the questionnaire were developed via
      a qualitative, telephone interview process. Data were analyzed using factor
      analysis and reliability analysis for scale development, and analysis of variance
      for preliminary validity assessment. RESULTS: Through factor analysis, the
      questionnaire was reduced from 84 to 52 items, and eight scales were examined:
      expected treatment benefits, expected treatment risks (short- and long-term),
      expected treatment inconveniences, value of treatment benefits, value of risks
      (short- and long-term), and value of treatment inconveniences. For parents, the
      reliability for all scales was in the acceptable range. For orthodontists, only
      the "short-term risks" scale failed to attain an acceptable reliability.
      Preliminary validity was assessed through examining relationships between
      demographic variables and subscale scores. For parents, income, father's
      education level, and sex of respondent were related to treatment expectations and
      values. For orthodontists, age, sex, and patient volume were related to treatment
      values. CONCLUSIONS: The questionnaire developed in the present study was found
      to be practical and reliable for use with providers and consumers of orthodontic
      care and can be used to explore factors affecting the demand for orthodontic
      care. Implications of possible unrealistic treatment expectations on the part of
      orthodontists and parents also are discussed.

PMID- 9558626
TI  - Comparing the impact of oral disease in two populations of older adults:
      application of the geriatric oral health assessment index.
AB  - OBJECTIVES: This study compares the distributional and psychometric properties of
      the Geriatric Oral Health Assessment Index (GOHAI) in two samples of older
      adults, and examines how the self-perceived impact of oral disease, as measured
      by the GOHAI, varies in accordance with sample sociodemographic and health
      characteristics. METHODS: Results are based on survey data from two samples of
      older men: a Medicare sample of patients using community physicians (n = 799;
      mean age = 74) and users of VA ambulatory health care (n = 542; mean age = 72).
      RESULTS: The findings indicate significant differences between samples in mean
      GOHAI scores, with the VA sample exhibiting worse scores. A number of
      similarities in psychometric properties of the instrument across the two samples
      were found: high internal consistency reliability and similar inter-item and item
      scale correlations. Factors analyses revealed somewhat different structures
      between the two samples, but explained similar amounts of variance; regression
      analyses indicated that income and self-rated oral health were significant
      predictors of GOHAI scores in both samples. CONCLUSIONS: The GOHAI exhibits
      satisfactory psychometric properties in both samples of older men. Results
      suggest continued use of the GOHAI as an indicator of the impact of oral
      conditions on functioning and well-being in a variety of samples.

PMID- 9558628
TI  - Restorative certainty and varying perceptions of dental caries depth among
      dentists.
AB  - OBJECTIVE: The question of whether dentists who most frequently identify tooth
      surfaces for definite restoration perceive dental caries as significantly deeper
      than other dentists is assessed. METHODS: One group of 20 dentists independently
      examined 145 unrestored approximal tooth surfaces on 16 bitewing radiographs and
      recorded their restorative and depth decisions. Another group of 15 dentists
      similarly scored 304 unrestored surfaces on 30 bitewing radiographs. Each group
      of dentists was later divided into four subgroups according to the number of
      surfaces designated for definite restoration by each dentist. RESULTS: As the
      number of tooth surfaces designated for definite restoration increased, mean
      caries depth (P < .05 for the high vs low subgroups) and the percent of
      dentinally carious surfaces increased, while the percent of surfaces assessed as
      sound decreased. Dentists with the lower numbers of surfaces designated for
      definite restoration came closest to the true histologic mean caries depth of the
      examined tooth surfaces. CONCLUSIONS: Dentists who designated high numbers of
      approximal tooth surfaces for definite restoration assessed caries as deeper than
      other dentists, and deeper than was proven histologically.

PMID- 9558627
TI  - Evaluation and use of an index of oral health status.
AB  - OBJECTIVES: The goals of this investigation were (1) to evaluate the Oral Health
      Status Index in relation to demographic characteristics, socioeconomic status,
      and preventive behaviors of an adult population; and (2) to understand how
      individual index components performed as indicators of oral health status
      compared to the composite index. METHODS: The Oral Health Status Index (OHSI) was
      used on a probability sample of adults, aged 18-93 years, living in the Detroit
      tricounty area. Data were collected on 509 subjects via in-home dental
      examinations. Bivariate and multivariate analyses were used to compare the OHSI
      and its components, including decayed, missing, and replaced teeth, free ends,
      and moderate and severe periodontal disease measures. RESULTS: The mean OHSI
      score for subjects was 77.3 (SE = 1.83) with a range of -8.0 to 100.0. In
      regression analyses, OHSI scores were positively correlated with subjects'
      education level, self-rated oral health scores, and frequency of dental checkups
      and negatively correlated with age, nonwhite race, and smoking. Of the index
      components, missing teeth performed well as an indicator of oral health status.
      Missing teeth were positively correlated with age, nonwhite race, and smoking and
      negatively correlated with education level, self-rated oral health, and use of
      Medicaid. About 53 percent of variance in OHSI scores was explained by the
      multivariate models, compared to 46 percent for missing teeth. CONCLUSIONS:
      Choosing an indicator of oral health status likely will depend upon the
      characteristics of the population to be studied. As a composite measure of oral
      health status, the OHSI performed acceptably; however, missing teeth, an index
      component, also worked well. Continued evaluation of the OHSI is warranted.

PMID- 9558629
TI  - [Is otoacoustic emission useful in the differential diagnosis of occupational
      noise-induced hearing loss?].
AB  - It is very difficult to distinguish between occupational noise-induced hearing
      loss and other diseases with cochlear hearing loss by the means of conventional
      audiometric tests. Otoacoustic emission measurement is a relatively new tool for
      assessing the inner ear function. It gives an opportunity of monitoring the
      status of the outer hair cells, the elements which are the most sensitive to
      noise-induced damage. In this study the results of distortion product otoacoustic
      emission (DPOAE) measurement in subjects with industrial noise-induced hearing
      loss, presbycusis and hearing impairment caused by gentamycin, are presented. In
      all these cases pure-tone audiometry revealed similar shape of the audiograms
      with cochlear hearing loss mainly at high frequencies. In the cases of industrial
      noise-induced hearing loss, DPOAE measurements demonstrated a very typical shape
      of DP-gram with the decrease (notch) in otoacoustic primarily at the frequencies
      of 3-4 kHz. Such a notch in DP-grams was not observed in the cochlear hearing
      loss caused by factors other than noise. The data indicate that otoacoustic
      emissions may be useful in the differential diagnosis of occupational noise
      induced hearing loss.

PMID- 9558630
TI  - [Evaluation of dynamic changes in hearing impairment in subjects exposed to noise
      while testing for transient evoked otoacoustic emission].
AB  - A group of 74 miners, aged 19-35 years, exposed to industrial noise at average
      level of 82-88 dBA for 1.5 to 15 years were examined by means of otoacoustic
      emission (TEOAE). The group was divided into three subgroups, depending on the
      duration of noise exposure. The results obtained in miners were compared to the
      results of the control group nonexposed to noise at the workplace. Otoacoustic
      emission was weaker in subjects exposed to noise. Significant differences in
      responses were found in subgroups II and III as compared to controls. The results
      were compared to the data reported by other authors. The role of otoacoustic
      emission in providing information about dynamics changes in hearing impairment,
      depending on the duration of noise exposure, in subjects exposed to industrial
      noise, was emphasised.

PMID- 9558631
TI  - [Analysis of accidents in selected occupations in the Szczecin shipyard S.A. in
      the years 1989-93].
AB  - In a five-year follow-up study (1989-93), 1317 work-related accidents and their
      relation to occupational exposure among male workers employed at the Szczecin
      Shipyard were analysed. The highest rates of accidents were found among welders,
      fitters, electrical mechanics and platers. The role of the age, duration of
      employment, type of the job performed and its contribution to the rate and
      pattern of accidents, were also investigated.

PMID- 9558632
TI  - [Evaluation of patient exposure to radiation during x-ray diagnostic examinations
      (in selected health service centers in the city of Wroclaw and in the province of
      Wroclaw)].
AB  - In 35 x-ray laboratories, randomly selected, in the city of Wroclaw an in the
      voivodship, the following measurements were performed: -exposure doses (mGy) for
      different kinds of x-ray examinations, -exposure doses (mGy) for examinations
      employing conventional intensifying cassettes and cassettes equipped with
      intensifying screens of rare earths, -basic exposure parameters, ie high voltage
      (kV), anodic current intensity (mA), and exposure duration. An average number of
      exposure per one examination was also defined. The values of standard deviation
      (SD) for doses measured and for exposure parameters were identified. The doses
      were compared with the values recommended in "Basic Safety Standards for
      Protection Against Ionizing Radiation" (IAEA, Safety Series No 115). Two
      differences were discussed between the values measured and those recommended,
      particularly in exposures when conventional cassettes were used. The assessment
      of exposure parameters for the same x-ray examinations performed in different
      laboratories pointed to a lack of any analogy between the results. It bears
      witness to the fact that x-ray equipment is very much diversified, and that
      subjective factors play a significant role.

PMID- 9558634
TI  - [Evaluation of the carcinogenic effect of ceramic fibers in experiments on rats
      and mice].
AB  - The carcinogenic effect of Kaowoll raw and thermally used ceramic fibres was
      assessed in experiments on rats and mice. The fibers were applied
      intraperitoneally in doses by 25 and 5 mg, and the animals were observed over
      their life-span. It was found that Kaowoll fibers were carcinogenic and that high
      temperature did not change these properties.

PMID- 9558633
TI  - [A quantitative assessment of health risk induced by occupational exposure to
      inorganic arsenic].
AB  - The risk of neoplastic disease, primarily lung cancer, induced by occupational,
      inhalation exposure to nonorganic arsenic was assessed. In order to identify
      individual risk in the linear dose-response relationship which would serve as a
      basis for the risk assessment among persons exposed occupationally, the author
      also analysed the latest epidemiological studies performed in Sweden, as well as
      repeated analyses of American studies. This allowed to diminish individual risk
      by several times. It is thought that a diminished value of individual risk is, in
      the light of the most up-to-date epidemiological studies, closer to the reality
      than the value proposed by the Environmental Protection Agency (EPA). Having the
      value of individual risk related to occupational exposure, equal 1.79 x 10(-4),
      lung cancer risk after forty years of employment under the exposure level within
      the range of currently binding MAC values for arsenic (0.05 mg/m3) accounts for
      8.95 x 10(-3), thus slightly exceeding the adopted value of 1 x 10(3). Whereas a
      new value, proposed by the Expert Group for Chemical Factors of the International
      Commission for Updating the list of MAC and MAI values in 1996, equals 0.01, so
      the risk for a forty-year employment accounts for 1.79 x 10(-3), in fact the
      value corresponding to that already approved. In addition, the assessment
      indicated that smoking increases by 4-6 times the risk of lung cancer induced by
      exposure to arsenic.

PMID- 9558635
TI  - [The effect of stress in the workplace on the risk of ischemic heart diseases-
      the role of epidemiologic studies].
AB  - Among numerous areas of occupational medicine, the studies of the impact of
      psychosocial factors on the development of cardiovascular diseases have been
      progressing most rapidly. The role of epidemiological studies in analysing the
      effect of this group of stressors on the incidence of ischaemic heart disease is
      discussed. The most significant outcome of the studies regarding selected
      psychological reactions referred to Karasek and Theorell's model of psychic
      burden/control, the role of life events, A type behavior and other selected
      personality changes. The authors stress that issues such as so called 'selection
      phenomenon', adequate size of the populations investigated, accurate selection of
      measurement methods, control of confounding factors and the cause-effect
      inference based on cross-sectional studies, are the major limitations in
      epidemiological studies of the effect of occupational stress on the state of
      health. Further progress in this area depends on how far these limitations could
      be overcome.

PMID- 9558636
TI  - [Allergic conditions for diseases of the respiratory tract from occupational
      exposure to acid anhydrides].
AB  - Acid anhydrides are highly reactive, low molecular weight compounds that are used
      widely in industry. Work-related exposure to this group of substances may cause
      occupational asthma. Because of low molecular weight, these compounds are not
      able to induce antibody responses without conjugating with human proteins. Acid
      anhydrides may act as haptens when conjugated with human serum albumin (HSA). The
      induction mechanism of immediate and late bronchial hyperresponsiveness to acid
      anhydrides appears to be at least partly mediated by IgE antibodies. Other
      clinical syndromes, which may be caused by acid anhydrides such as pulmonary
      disease-anemia (PDA), and late respiratory systemic syndrome (LRSS) associated
      with TMA exposure, appear to be associated with IgG antibodies to TMA as well as
      with IgE. Significant cross-reaction occurs between different compounds of this
      group, particularly regarding IgE antibodies. As inhalational exposure to acid
      anhydrides may result in serious pulmonary disease, adequate protection of
      potentially exposed workers or their removal, if affected, from exposure is
      essential.

PMID- 9558637
TI  - [Some issues regarding the use of electroencephalography and brain evoked
      potentials in occupational medicine].
AB  - On the basis of the literature data, the practical value of
      electroencephalography (EEG) and tests of brain evoked potentials, particularly
      visual evoked potentials (VEP) and somatosensory evoked potentials (SSEP) in the
      diagnosis of occupational diseases of the nervous system is discussed.
      Electroencephalographic changes and the results of the evoked potential tests
      performed in persons exposed to organic solvents and heavy metals are analysed.
      The author postulates how the research in this field should be oriented and
      stresses the need to incorporate the method of evoked potentials into diagnostic
      procedures, especially in the case early symptoms of the nervous system
      dysfunction induced by occupational factors.

PMID- 9558638
TI  - [Actual and perspective activities of the European Union concerning protection
      against noise].
AB  - In most industrialised countries exposure to noise is one of major health
      problems which, because of its social and economic dimension has been given
      priority in the area of preventive activities. It is estimated that only in
      Europe about 25-30 million people are employed in conditions under exposure to
      noise at excessive levels, harmful to the hearing organ, generating the risk of
      hearing loss (disability), and in consequence limiting the possibility of active
      life. Acknowledging the significance of the problem and its consequences the
      World Health Organization (WHO) in cooperation with the International (ISA) and
      European Federation of Audiological Society (EFAS) has developed the programme
      for the protection against noise. The prime aims of the programme are to
      establish the cooperation between scientists, health services and technicians in
      order to promote knowledge and exchange of experience, to improve workers'
      health, and to identify the biological, neuropsychological and psycho-social
      effect of noise exposure on the hearing ability. The authors discuss basic
      objectives and adopted strategies of experimental and clinical studies carried
      out in countries of the European Union, participating in the implementation of
      the programme. The WHO guidelines for the reduction in noise exposure in the
      working, municipal and recreation environments are also presented.

PMID- 9558639
TI  - [Individual autonomy and the principles of occupational health care].
AB  - The effect of work-related diseases on the health condition of the population at
      large has increased the interest in etiology and epidemiology of these diseases
      and intensified activities aimed at providing effective treatment of occupational
      diseases, but first of all at preventing their occurrence. That is why workers
      are now recognised as the largest population group subjected to active
      counselling. In order to meet the recommendations of the International Labour
      Organization, Polish labour law has been modified so that every worker is
      guaranteed an opportunity to benefit from medical prevention within the range
      required by his/her working conditions. This concern for workers' health
      contributed to the fact that health has now become a supreme value to which all
      other values and human needs are submitted. The author discusses the issues of
      compulsory prophylactic examinations and protection against employment at a
      workplace that is inadmissible because of health reasons, in the perspective of
      the human right to keep his/her own ailments in secret and the right to freedom
      of choice concerning his/her own health and living and conditions.

PMID- 9558640
TI  - [Costs and benefits of medical prevention in small enterprises].
AB  - The current transformation of Polish economy towards free market compels a
      rational management of resources and more effective instruments for the cost
      benefit control in small enterprises. One of the most important areas of
      activities in small enterprises is the promotion of medical prevention at the
      workplace. Employers are committed to ensure that all workers have access and
      benefit from medical prevention, as well as to bear all costs involved in
      prevention programmes, periodical prophylactic examinations, and actions aimed at
      promoting workers' health and improving working conditions. Planning these
      improvements, health certificates and recommendations resulting from the
      evaluation of working conditions should be taken into consideration. New legal
      regulations create the ground for employers to choose the most effective and
      appropriate measures for providing preventive care. The aim of the study was to
      elaborate and implement the cost-benefit analysis of medical prevention
      activities in enterprises, thought as one of decision-making tools to be used by
      employers. The principles of the cost-benefit analysis in enterprises algorithm
      of proceedings and the instructions how the analysis should be implemented, were
      elaborated. In addition, a supportive computer system was developed. The cost
      benefit analysis was already implemented as a pilot project in several
      enterprises what helped to modify the method and collect numerical data necessary
      to perform the analysis and to define the scope of its application.

PMID- 9558641
TI  - Speed-dependent motion-sensitive responses in V5: an fMRI study.
AB  - This fMRI study examined motion-sensitive responses in human area V5 as a
      function of stimulus speed. Consistent with electrophysiological findings, we
      observed optimal responses at intermediate speeds of around 7 degrees/s to 30
      degrees/s. The results are consistent with a nonlinear (inverted "U") dependency
      on speed that was also observed in V3a. V1 activation was observed to decrease
      linearly as speed increased. This is consistent with the fact that speed
      sensitive cells in V1 have been shown to be tuned to much slower speeds than in
      V5.

PMID- 9558642
TI  - Mapping voxel-based statistical power on parametric images.
AB  - Using a classic technique based on the noncentral F-distribution method for
      computing statistical power, we developed a general approach to the estimation of
      voxel-based power in functional brain image data analysis. We applied this method
      to PET data from a large sample (N = 40) of subjects performing the Wisconsin
      Card Sorting (WCST) paradigm analyzed with SPM95, produced statistical power maps
      for a range of samples sizes and smoothing filter widths, and examined the
      effects of sample size and image smoothing on the expected reliability of
      activation findings. At an uncorrected alpha of 0.01, a fixed filter size of 10
      mm3, and a range of power thresholds, maps revealed that the power to reject the
      null hypothesis in brain regions implicated in the task at Ns of 5 and 10 may not
      be sufficient to ensure reliable replication of significant findings and so
      should be interpreted with caution. At sample sizes approaching 20 subjects,
      sufficient power was found in the right dorsolateral prefrontal cortex (BA 46/9),
      right and left inferior parietal lobule (BA 40), and left inferior temporal lobe
      (BA 37), comprising the cortical network typically observed during the WCST.
      Filter size needed to maximize power varied widely, but systematically, across
      the brain, tending to follow known neuroanatomical landmarks. Statistical power
      considerations in brain imaging studies are critical for controlling the rate of
      false negatives and assuring reliable detection of cognitive activation. The
      variation of filter size for maximizing power across the brain suggests that the
      underlying neuroanatomy of functional units is an important consideration in the
      a priori selection of filter size.

PMID- 9558643
TI  - Nonlinear aspects of the BOLD response in functional MRI.
AB  - Functional magnetic resonance imaging (fMRI) using blood oxygenation level
      dependent (BOLD) contrast has progressed rapidly and is commonly used to study
      function in many regions of the human brain. This paper introduces a method for
      characterizing the linear and nonlinear properties of the hemodynamic response.
      Such characterization is essential for accurate prediction of time-course
      behavior. Linearity of the BOLD response was examined in the primary visual
      cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2,
      4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s
      duration) were used to test the hemodynamic response. Superposition of the
      obtained responses was performed to determine if the BOLD response is nonlinear.
      The nonlinear characteristics of the BOLD response were assessed using a
      Laplacian linear system model cascaded with a broadening function. Discrepancies
      between the model and the observed response provide an indirect measure of the
      nonlinearity of the response. The Laplacian linear system remained constant
      within subjects so the broadening function can be used to absorb nonlinearities
      in the response. The results show that visual stimulation under 4 s in duration
      and less than 40% contrast yield strong nonlinear responses.

PMID- 9558644
TI  - Functional connectivity in single and multislice echoplanar imaging using resting
      state fluctuations.
AB  - A previous report of correlations in low-frequency resting-state fluctuations
      between right and left hemisphere motor cortices in rapidly sampled single-slice
      echoplanar data is confirmed using a whole-body echoplanar MRI scanner at 1.5 T.
      These correlations are extended to lower sampling rate multislice echoplanar
      acquisitions and other right/left hemisphere-symmetric functional cortices. The
      specificity of the correlations in the lower sampling-rate acquisitions is lower
      due to cardiac and respiratory-cycle effects which are aliased into the pass-band
      of the low-pass filter. Data are combined for three normal right-handed male
      subjects. Correlations to left hemisphere motor cortex, visual cortex, and
      amygdala are measured in long resting-state scans.

PMID- 9558645
TI  - Functional clustering: identifying strongly interactive brain regions in
      neuroimaging data.
AB  - Brain imaging data are generally used to determine which brain regions are most
      active in an experimental paradigm or in a group of subjects. Theoretical
      considerations suggest that it would also be of interest to know which set of
      brain regions are most interactive in a given task or group of subjects. A subset
      of regions that are much more strongly interactive among themselves than with the
      rest of the brain is called here a functional cluster. Functional clustering can
      be assessed by calculating for each subset of brain regions a measure, the
      cluster index, obtained by dividing the statistical dependence within the subset
      by that between the subset and rest of the brain. A cluster index value near 1
      indicates a homogeneous system, while a high cluster index indicates that a
      subset of brain regions forms a distinct functional cluster. Within a functional
      cluster, individual brain regions are ranked at the center or at the periphery
      according to their statistical dependence with the rest of that cluster. The
      applicability of this approach has been tested on PET data obtained from normal
      and schizophrenic subjects performing a set of cognitive tasks. Analysis of the
      data reveals evidence of functional clustering. A comparative evaluation of which
      regions are more peripheral or more central suggests distinct differences between
      the two groups of subjects. We consider the applicability of this analysis to
      data obtained with imaging modalities offering higher temporal resolution than
      PET.

PMID- 9558646
TI  - [Mechanism of cellular cholesterol removal: a communication system between
      extracellular cholesterol transport and intracellular cholesterol homeostasis].
AB  - Cholesterol efflux is one of the essential events in cellular cholesterol
      homeostasis since peripheral cells do not catabolize the cholesterol molecule.
      There are two distinct mechanisms for the efflux. One is the non-specific
      classical pathway mediated by physicochemical diffusion of cholesterol through
      the aqueous phase and its esterification on high density lipoprotein (HDL) by
      lecithin: cholesterol acyltransferase (LCAT). The other is the specific and
      biological pathway in which new HDL particles are generated from cellular lipid
      by the direct interaction of cell membrane and amphiphilic apolipoproteins that
      have dissociated from HDL. The latter reaction consists of binding of
      apolipoprotein to the specific binding site of the cellular surface and
      subsequent mobilization of intracellular cholesterol for the HDL generation
      mediated by intracellular signal transduction. This reaction seems to be a major
      source of plasma HDL.

PMID- 9558647
TI  - [Role of nitric oxide in learning and memory processes].
AB  - Nitric oxide (NO) is a free radical gas that is synthesized from L-arginine by NO
      synthase (NOS). Activation of NMDA, non-NMDA or metabotropic glutamate receptors
      causes NO formation through NOS activation. From data obtained in experiments
      performed by microdialysis together with nitrate assay, we have proposed that NO
      production in the cerebellum following non-NMDA and metabotropic glutamate
      receptor activation may be independent of NOS activity, while NMDA receptor
      mediated NO production depends on its activity. Glial cells appear to play a role
      in modulating NO production by regulating L-arginine availability. Activation of
      NMDA receptors and the increase in intracellular calcium concentration is a
      trigger for the long-term potentiation (LTP). NO acts as a retrograde messenger
      in the hippocampal LTP to enhance glutamate release from presynaptic nerve
      terminal, in which cyclic GMP may be involved. Behavioral studies demonstrate
      that NO is involved in some forms of learning and memory. Our studies suggest
      that NMDA/NO/cyclic GMP signaling plays a role in spatial working memory.
      Further, it is suggested that NO production in the brain is altered by aging.
      These results support the hypothesis that NO plays a role in mechanism of
      synaptic plasticity.

PMID- 9558648
TI  - [Techniques for evaluating neuronal death of the retina in vitro and in vivo].
AB  - This review describes the techniques to evaluate retinal neurodegeneration
      induced by excitatory amino acids and transient ischemia. Glutamate-induced
      neurotoxicity was examined in cultured rat cortical cells. Cultures obtained from
      the retinas of fetal rats were incubated in Eagle's minimal essential medium
      supplemented with 10% fetal calf serum or 10% horse serum at 37 degrees C in a
      humidified 5% CO2 atmosphere for 10-14 days. The neurotoxicity induced by
      glutamate was quantified by trypan blue exclusion. The viability of cultures was
      markedly reduced by a 10-min exposure to glutamate followed by incubation with
      glutamate-free medium for 1 hr. N-methyl-D-aspartate (NMDA)-induced retinal
      damage was examined in adult rats. Transverse sections of the retinas through the
      optic disk were stained with hematoxylin and eosin. A single intravitreal
      injection of NMDA damaged the ganglion cell layer and the inner plexiform layer
      without affecting the other retinal layers 7 days after injection. Retinal
      ischemia was induced by elevating the intraocular pressure for 45 min through the
      needle which was placed in the anterior chamber. Ischemia-induced retinal damage
      was inhibited by MK-801. These results indicate that the techniques described in
      this review can be employed to develop new drugs possessing neuroprotective
      action against neurodegeneration that occurs during retinal ischemia.

PMID- 9558649
TI  - [Effects of KB-R7943, a novel Na+/Ca2+ exchange inhibitor, on myocardial
      ischemia/reperfusion injury].
AB  - The effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea
      methanesulfonate) on major ion transporters were studied in canine cardiac
      sarcolemmal and sarcoplasmic reticular vesicles. KB-R7943 inhibited the Na+/Ca2+
      exchange more potently than the Na+/H+ exchange, the Na+/K(+)-ATPase and the
      Ca2(+)-ATPase. The effects of KB-R7943 on ischemia/reperfusion-induced injury
      were studied in isolated rat perfused hearts in comparison with those of
      diltiazem and lidocaine. In normal hearts, diltiazem (10 microM) and lidocaine
      (100 microM) markedly reduced contractile function, but KB-R7943 (1, 10 microM)
      had no such effect. In the hearts subjected to 25-min ischemia and 30-min
      reperfusion, KB-R7943 concentration-dependently and significantly improved post
      ischemic recovery of left ventricular developed pressure, left ventricular
      dP/dtmax and left ventricular end-diastolic pressure by pre-ischemic treatment (5
      min) or post-ischemic treatment (10 min). Diltiazem and lidocaine showed similar
      improvement of recovery by pre-ischemic treatment, but they had no effect by post
      ischemic treatment. Furthermore, the effect of KB-R7943 on arrhythmia was studied
      in anesthetized rats subjected to 5-min cardiac ischmeia and 10-min reperfusion.
      KB-R7943 (1, 10 mg/kg, i.v.) dose-dependently reduced the incidence and the
      duration of ventricular fibrillation. These results indicate that KB-R7943, a
      selective Na+/Ca2+ exchange inhibitor, has beneficial effects against myocardial
      ischemia/reperfusion injury and suggest that activation of the Na+/Ca2+ exchange
      mainly occurs immediately after reperfusion in the pathophysiological process of
      myocardial ischemia/reperfusion injury.

PMID- 9558650
TI  - [Effect of liver hydrolysate on ethanol- and acetaldehyde-induced deficiencies].
AB  - Since it has been reported that amino acids have alleviating effects on ethanol-
      and acetaldehyde-induced toxicity, we investigated the effect of liver
      hydrolysate derived from bovine liver on ethanol- or acetaldehyde-induced
      toxicity and deficiency models of mice and rats in the present study. Liver
      hydrolysate improved the deficiencies of beam walking and food intake of mice in
      a dose-dependent fashion when challenged with ethanol at the dose of 5 ml/kg,
      p.o. According to the analysis using selective inhibitors for alcohol
      dehydrogenase and acetaldehyde dehydrogenase, it has been suggested that this
      improvement effect of liver hydrolysate is mainly due to the reduction of
      acetaldehyde toxicity. No effect of liver hydrolysate was found in coma and death
      produced by orally treated ethanol at 10 ml/kg. In contrast, liver hydrolysate
      dose-dependently decreased the coma and death of mice administered acetaldehyde
      at 1.8 ml/kg, p.o. Furthermore, an increase in serum GPT activity, which was
      caused by twice oral administration of acetaldehyde at 1.2 ml/kg at interval of 1
      hr, was inhibited by liver hydrolysate. These results suggest that liver
      hydrolysate has a protective effect against ethanol- and acetaldehyde-induced
      toxicity.

PMID- 9558651
TI  - [Neurosurgery and molecular biology: (series 1) basic knowledge for understanding
      molecular biology of the cell].

PMID- 9558652
TI  - [Carotid endarterectomy: recent controversies].

PMID- 9558653
TI  - [Usefulness of multiple burr-hole operation for child Moyamoya disease].
AB  - Excellent results of multiple burr-hole operation (MBHO) for child moyamoya
      disease are reported in this study. Three patients of moyamoya disease had MBHO.
      After MBHO, transient, ischemic attacks disappeared in a patient despite
      progressing stenosis of the major cerebral arteries, and remarkable neurological
      improvement was recognized in a patient who had encephaloduroarteriosynangiosis.
      Another patient slowly improved and became able to go to junior high school. N
      isopropyl-p-[123I] iodoamphetamine (IMPSPECT) findings also improved in all
      patients. There was no mortality or morbidity, and no new neurological deficits
      or bleedings developed during the follow up period. The authors recommend the
      MBHO as the surgical treatment of choice for not only adult but also child
      moyamoya disease because of its safety and effectiveness, and also report the
      usefulness of MBHO for the patients who have already received other bypass
      operations.

PMID- 9558654
TI  - [Subarachnoid hemorrhage in 'Vital Statistics of Japan', 1993-1995: variability
      with age and sex].
AB  - The incidence and death rate of subarachnoid hemorrhage (SAH) varies with age and
      sex. Female preponderance in the incidence of SAH is a well-known fact. However,
      the degree varies with age. Autopsy data, records of natural history of
      unruptured aneurysms, epidemiological and clinical cooperative studies have
      provided a great amount of information regarding the statistics of subarachnoid
      hemorrhage. But, each individual study has its own limitation, such as a bias in
      case selection in autopsy or clinical studies, predominance of aged population in
      the epidemiological cohort studies, limited frequency in the detection of
      unruptured aneurysms in the entire population. These shortcomings are reflected
      in the variability in the statistical data of these studies. Death records in
      'Vital Statistics of Japan', published annually by Ministry of Health and Welfare
      of Japan, exhibit the numbers of deaths by cause (according to ICD-9 or 10 code),
      sex and age. In this study, we calculated the death rates of SAH (per 100,000) in
      1993-1995 for each age group of both sexes based on the published data. Deaths
      from breast cancers and automobile accidents (AMA) were assessed in the same
      manner and compared with the results of SAH. The annual death rate of SAH for all
      people in Japan is 10.7 per 100,000 population and the average age of death is
      65.6 y.o. The death rate is 8.2 for men, and 13.1 for women. Average age at the
      death is 60.2 y.o. in men, and 68.8 y.o. in women (p < 0.001). The age-adjusted
      death rate to 1985 Japanese population was 7.3 for men and 9.2 for women. Below
      age 60, rate of death caused by SAH is higher for men than women, but the ratio
      reverses in the population over 60. For men, the death rates after the age of 40,
      50, 60 and 70 were 16.4, 20.4, 24.1 and 29.2 respectively. For women, the rates
      were 25.0, 32.8, 44.1 and 62.4. The female-to-male ratio of the death rates
      increases with age. Female sex should be considered as a risk factor for death
      from SAH. Number of deaths from breast cancers was about 90% of those from SAH in
      women. There was a difference in the age distribution; deaths caused by breast
      cancer tend to occur in younger age than those caused by SAHs. Mean age of death
      was 59.3 for breast cancer and 68.8 for SAH. Deaths caused by SAH is 1.4 times
      more likely to occur than those by breast cancer for a 50 year-old woman for the
      rest of her life, 1.9 times for a 60 y.o. woman, and 2.7 times for a 70 y.o.
      woman. Regular examination to detect breast cancer is widely performed in Japan
      among elderly women. We believe that a similar screening effort should be
      targeted for unruptured aneurysms from the standpoint of the medico-social cost.
      Automobile accidents (AMA) victimize as many people as SAH in Japan, about 13,000
      per year. For males over the age of forty, AMA victims are more than those from
      SAH. However, conversely females' deaths from SAH occur three times frequently as
      those from AMAs. The fact should be taken into consideration when screening for
      unruptured aneurysms.

PMID- 9558655
TI  - [Treatment of tuberculous meningitis: marker of cure].
AB  - A 49-year-old male with tuberculous meningitis was reported. When admitted to our
      hospital with mild right hemiparesis, he was alert but he developed
      disorientation 7 days later. A diagnosis of tuberculous meningitis was reached
      because of elevated levels of adenosine-deaminase at 19.6U/liter in the
      cerebrospinal fluid. MRI showed a marked enhancement in the basal cisterns and an
      enhanced intraparenchymal lesion in the brainstem. Chronological changes of MRI
      findings did not closely correlate with the clinical course. Slight meningeal
      enhancement on MRI seems to remain for a long time without active tuberculous
      meningitis, and absence of the meningeal enhancement on MRI is not necessarily
      appropriate as a marker of cure of tuberculous meningitis.

PMID- 9558656
TI  - [A case of hemangiopericytoma with multiple extracranial metastasis: a case
      report].
AB  - A case of a patient with hemangiopericytoma with multiple extracranial
      metastasis, who has survived for more than twenty years is reported. A fifty-five
      year-old male presented brain tumor twenty years ago. He underwent total removal
      of the tumors, but recurrences occurred each time. Liver metastasis was found
      seven years ago. After that multiple metastases extended to the lung, vertebra
      and pancreas and operations and irradiations were performed. At present, there is
      no progression of the tumors and he enjoyed a high quality of life. We concluded
      that, to ensure long time survival, a patient with hemangiopericytoma must be
      monitored carefully for local recurrence and systemic metastases.

PMID- 9558657
TI  - [Intratumoral hemorrhage associated with cystic meningioma under observation: a
      case report].
AB  - Cystic meningiomas are not commonly encountered and are said to account for only
      1 to 2% of all types of meningioma. There have been several reports on them and
      most of them were discussed under the aspect of the mechanism of cystic
      formation. Though few reports present the process of cystic formation, here we
      were able to present the process of cystic formation with intratumoral
      hemorrhage. The case was a 56-year-old man who presented with urinary
      incontinence. MRI revealed a large cystic tumor in the right frontal lobe and he
      was admitted to another hospital. After 20 days, MRI incidentally revealed
      hematoma near the intratumoral cyst. Two weeks later, MRI revealed that the
      hematoma flowed out the cyst and the cavity of the hematoma communicated with the
      cyst. Angiography showed that the tumor was fed by the left anterior ethmoid
      artery. After surgical removal of the tumor, histopathological diagnosis was that
      the tumor was a transitional meningioma and there were no findings of malignancy.
      Commonly, intratumoral hemorrhage is unusual for a meningioma but we suspect that
      there are not a few cases in which small hemorrhage occurred without symptoms and
      the hematoma cavity joined the intratumoral cyst while the cyst grew gradually.

PMID- 9558658
TI  - [Superior sagittal sinus occlusion due to calvarial metastasis of renal cell
      carcinoma: 2 cases report].
AB  - We report two cases of superior sagittal sinus (SSS) occlusion due to calvarial
      metastasis of renal cell carcinoma. Both cases were presented with bulging of the
      skull. No stigmata of increased intracranial pressure was detected. Cerebral
      angiogram showed the occlusion of the SSS. Tumor cells did not penetrate into the
      dura mater nor the galea and the tumors were able to be removed easily in both
      cases. One case without collateral circulation showed recanalization of the SSS
      on the postoperative angiography. Another case with development of collateral
      circulation did not show recanalization of SSS on the postoperative magnetic
      resonance angiography. In the latter case, cortical veins flowed into the
      occluded portion. We consider that SSS should be preserved to prevent venous
      congestion in the cases where collateral circulation has not developed.

PMID- 9558659
TI  - [Neurinoma arising from the first branch of the trigeminal nerve: a case report].
AB  - A case of a neurinoma arising from the first branch of the trigeminal nerve in a
      40-year-old female is reported. The patient was admitted with the chief complaint
      of loss of Lt. visual acuity and mild hypoesthesia in the area of the first
      branch of the trigeminal nerve. A CT scan and MRI revealed a tumor extending
      through the superior orbital fissure into the orbita. Subtotal resection of the
      tumor was performed by a fronto-orbito-zigomatic approach and a histological
      diagnosis of neurinoma was made. Although the hypoesthesia remained, the visual
      acuity was markedly improved postoperatively. A neurinoma arising from the first
      branch of the trigeminal nerve is very rare. To our knowledge, including our
      case, only five cases which were described for clinical and diagnostic features
      and surgical management have been reported. There were three males and two
      females, and the age ranged from 1 to 57 years. Neurologically, all cases
      presented hypoesthesia in the area of the first branch of the trigeminal nerve
      and exophthalmus on admission. Visual disturbance was found in three cases.
      Radiologically, the enlargement of the superior orbital fissure was revealed in
      two cases. Angiography performed in three cases demonstrated the avascular mass.
      Three patients received CT scan and only the present case used MR imaging.
      Surgical resection was performed in all cases through various approaches. The
      fronto-orbito-zygomatic approach which was chosen in our case was useful for
      obtaining a sufficient operative view. As in our case, excellent outcome was
      achieved in three other cases due to successful tumor resection.

PMID- 9558660
TI  - [A case of clear cell meningioma originating from the cerebellar tentorium].
AB  - We report herein on a case of clear cell meningioma originating from the
      cerebellar tentorium, surgically treated by occipital transtentorial approach
      (OTT). A 67-year-old woman was admitted to our hospital in September, 1996,
      complaining of gait disturbance. MRI revealed an isointense mass on T1 and T2 WI,
      clearly enhanced with gadolinium in the right upper cerebellum originating from
      the tentorium. A left vertebral angiogram showed tumor stain from the right
      superior cerebellar artery. The tumor was subtotally removed by OTT on September
      24, 1996. Gamma knife radiosurgery was performed for regrowing tumor 6 months
      after surgery. Histological examination revealed that the tumors were composed of
      sheets of clear, glycogen-rich cells and lobulated by thin connective tissues.
      There were no malignant findings, but some tumor cells had infiltrated into the
      cerebellar cortex. Immunohistochemistry showed that tumor cells were positive for
      EMA and vimentin, but negative for keratin. MIB-1 staining index was 7.02%. From
      these findings, this case was diagnosed as a typical clear cell meningioma
      originating from the cerebellar tentorium. From a review of the literature
      including our case, clear cell meningioma may be clinicopathologically malignant,
      so careful follow-up will be necessary.

PMID- 9558661
TI  - [Transsphenoidal surgery and gamma-knife radiosurgery for a treatment of
      recurrent craniopharyngioma with moyamoya vessels].
AB  - A recurrent craniopharyngioma associated with moyamoya vessels was successfully
      treated by partial removal of the tumor via the transsphenoidal approach followed
      by gamma-knife radiosurgery. This 19-year-old man was first treated by partial
      tumor removal and radiotherapy (54Gy) at the age of 6 years. Growth hormone and
      human chorionic gonadotropin were given from the ages of 13 to 18 years. At ag 17
      years, follow-up magnetic resonance imaging (MRI) revealed regrowth of the tumor.
      At the age of 19 years, he was readmitted for treatment of the enlarging remnant
      tumor. Neurological examination revealed bilateral blindness. MRI showed marked
      suprasellar, sphenoidal and bilateral cavernous sinus extension of the tumor.
      Angiography revealed stenosis of the right internal carotid artery and the M1 and
      A1 segments of the right cerebral arteries, as well as occlusion of the C3
      segment of the left internal carotid artery. There were vault and ethmoidal
      moyamoya vessels. The patient underwent tumor removal via the transsphenoidal
      approach, instead of craniotomy, to avoid injury to the transdural anastomosis.
      The intrasellar solid tumor was partially removed. The tumor was then irradiated
      by the gamma knife. MRI 15 months after the treatment showed marked reduction of
      the tumor. The pathogenesis of the moyamoya phenomenon and the choice of the
      treatment in this patient are discussed.

PMID- 9558663
TI  - Unilateral dermis-fat graft implantation in the pediatric orbit.
AB  - The purpose of this study was to evaluate the role of the dermis-fat graft (DFG)
      as an orbital implant in the pediatric age group. A retrospective study was made
      of a series of 16 patients who had undergone unilateral orbital implantation of a
      DFG. The ages of the patients at the time of surgery ranged from 2 months to 17
      years, with followup ranging from 2 to 15 years. Growth of the graft was
      clinically apparent in the younger children. Increasing proptosis required
      surgical debulking of the graft in six of eight children who were 4 years old or
      younger at the time of DFG implantation. None of the eight children who were 9
      years or older at the time of DFG implantation required surgical debulking.
      Indeed, five of the older patients demonstrated some degree of graft atrophy.
      Dermis-fat grafts placed in the orbits of young children appear to grow after
      implantation. This growth of the implant may help stimulate orbital growth,
      potentially leading to more symmetry between the involved and uninvolved sides.

PMID- 9558662
TI  - Rate of vascularization of coralline hydroxyapatite spherical implants pretreated
      with saline/gentamicin, rTGF-beta 2, and autogenous plasma.
AB  - Several authors have reported significant exposure rates using the hydroxyapatite
      orbital implant in the treatment of the anophthalmic socket. Histologic studies
      by ourselves and others have suggested that lack of fibrovascular ingrowth into
      the implants may contribute to conjunctival breakdown and exposure. Recently,
      much attention has been given to angiogenic factors, such as rTGF-beta 2 and
      those found in plasma, in accelerating wound healing and fibrovascular ingrowth.
      This pilot study compares the rate of vascularization of hydroxyapatite orbital
      implants pretreated with plasma, rTGF-beta 2, and a saline/gentamicin solution
      with that in untreated controls ina population of New Zealand albino rabbits.
      Hydroxyapatite orbital spheres were implanted subcutaneously and in enucleated
      orbits. Untreated implants were used as a control. Implants pretreated with
      plasma, rTGF-beta 2, and a saline/gentamicin solution were removed and examined
      histologically at weekly intervals for the first 3 weeks after implantation.
      Histologic studies demonstrated that the rate of vascularization significantly
      increased between 2 and 3 weeks postoperatively in all study groups. Pretreating
      the implants with rTGF-beta 2 in phosphate buffered solution (PBS) or autogenous
      plasma did not significantly increase the rate of vascularization in comparison
      with controls at weeks 1 and 2. However, pretreating the implants with a
      saline/gentamicin solution or PBS alone was associated with an increased rate of
      vascularization at weeks 2 and 3. No statistically significant difference in
      vascularization was noted between the subcutaneous and orbital implants at any
      week. Hydroxyapatite implants pretreated with saline/gentamicin or phosphate
      buffered solutions underwent more rapid vascularization at weeks 2 and 3 in
      comparison with controls. Additionally, all groups were noted to have a more
      rapid rate of ingrowth between weeks 2 and 3 than between weeks 1 and 2. Plasma
      and rTGF-beta 2 (at the dose used) did not significantly alter the rate of
      vascularization of hydroxyapatite implants during the first 2 to 3 weeks. The
      significance of these findings is discussed.

PMID- 9558664
TI  - Paralytic ectropion: a complication of malar implant surgery.
AB  - The use of the malar implant to augment the malar-zygomatic eminence is rapidly
      becoming a popular aesthetic procedure; however, this surgery can lead to
      paralysis or paresis of the facial nerve. Paralytic ectropion may result from
      orbicularis oculi dysfunction. We report two cases of paralytic ectropion as a
      result of malar implant placement. Conservative management for mild orbicularis
      oculi dysfunction consisted of topical lubricants and observation, whereas
      persistent ectropion required surgical repair. Paralytic ectropion and secondary
      exposure keratopathy are possible complications of malar implant surgery.

PMID- 9558665
TI  - A modified surgical technique in the treatment of facial nerve palsies.
AB  - The ophthalmic complications associated with facial nerve palsy present a
      challenging problem to the treating ophthalmologist. Over the last hundred years,
      a wide variety of techniques have been used to rehabilitate patients with facial
      nerve palsy. Each of these techniques is associated with unique complications. We
      describe a significantly modified surgical technique for the rehabilitation of
      patients with facial nerve palsy that has not, to our knowledge, previously
      appeared in the literature.

PMID- 9558666
TI  - Effectiveness of homologous cadaveric fascia lata and role of suture fixation to
      tarsus in frontalis suspension.
AB  - The results of frontalis suspension (double rhomboid technique with preserved
      homologous cadaver fascia) were compared in two surgical groups: 1) patients in
      whom the fascia was sutured to the tarsus and 2) patients in whom the fascia was
      not sutured to the tarsus. The study was performed to determine the optimum
      surgical technique and to determine whether preserved cadaver fascia is a
      suitable suspensory material. All data retrospectively reviewed included 1)
      predisposing cause of severe blepharoptosis, 2) results in the two groups of
      patients, suture fixation and nonsuture fixation, and 3) surgical complications.
      Of the 27 patients (36 eyelids), the fascia was sutured to the tarsus in 15
      patients (20 eyelids) and not sutured to the tarsus in 12 patients (16 eyelids).
      In the suture fixation group, no undercorrections occurred, but four of 20
      eyelids had lower than expected eyelid creases and six had residual
      dermatochalasis. Six patients had lagophthalmos with corneal exposure that
      required intense corneal lubrication, and three such patients required temporary
      tarsorrhaphy for 3 weeks. In the group without suture fixation, two patients had
      undercorrection (one with ocular cicatricial pemphigoid and the other with
      myotonic dystrophy). The mean followup period was 44 months. We conclude that
      preserved fascia provides excellent results with or without fixation of the
      fascia to the tarsus. In patients with suture fixation, the eyelid crease may
      form just above the point at which the fascia is sutured to tarsus and result in
      a low eyelid crease. Excision of excess skin should be considered at the time of
      frontalis suspension in selected patients in whom the fascia is fixated to the
      tarsus or who have preexisting dermatochalasis. Patients with suture fixation may
      have significant temporary postoperative lagophthalmos.

PMID- 9558667
TI  - Hering's law and eyebrow position.
AB  - A patient with bilateral but asymmetrical brow ptosis is presented in whom the
      frontalis action on the relative position of the eyebrows could be demonstrated
      to obey Hering's law of equal innervation. The neurological basis for this
      finding is discussed, along with the implications for the surgical management of
      brow ptosis.

PMID- 9558668
TI  - The endoscopic forehead lift.
AB  - Endoscopic techniques are being successfully applied to address eyebrow and
      forehead ptosis. The methods rely on extensive subperiosteal and subgaleal
      release of the forehead and scalp flap, allowing the elevation of soft tissues.
      Ablation of the depressor supercilli and procerus can be performed to address
      skin folding in the glabellar region. The mobilized frontotemporal flap is then
      elevated to the desired level and fixated with microscrews to the outer table of
      the skull. Laterally, the flap is fixed to the deep temporalis fascia. The
      technique relies upon a solid knowledge of the regional anatomy and the use of
      specialized instruments now available for dissecting under the flap. The
      endoscopic forehead lift can achieve results comparable to those obtained by the
      open coronal forehead lift while minimizing the incidence and extent of
      postoperative cutaneous anesthesia and telogenic hair loss, which frequently
      follows open coronal forehead surgery. In addition, the endoscopic technique is
      able to address eyebrow ptosis in the balding male without causing disfiguring
      scarring.

PMID- 9558669
TI  - Interleukin-8 and monocyte chemotactic protein-1 gene expression and protein
      production by human orbital fibroblasts.
AB  - Orbital inflammation is common, but the mechanisms underlying leukocytic
      infiltration of orbital tissue are poorly understood. We studied resident human
      orbital fibroblasts (OF) interleukin-8 (IL-8), and monocyte chemotactic protein-1
      (MCP-1) mRNA expression and protein secretion in response to lipopolysaccharide
      (LPS) or recombinant human cytokines that are present during inflammation. Third
      passaged cultured human OF were left unstimulated or incubated with varying
      concentrations of LPS, recombinant interleukin-1-beta (rIL-1 beta), recombinant
      tumor necrosis factor-alpha (rTNF-alpha), or recombinant interferon-gamma (rIFN
      gamma) for 2, 4, 8, or 24 h. Northern blot analysis and ELISA were performed to
      determine OFIL-8 and MCP-1 mRNA expression and protein secretion, respectively.
      Experiments were performed in triplicate and repeated four times on different
      cell lines. OF lacked constitutive IL-8 or MCP-1 gene expression, but produced
      substantial dose-dependent increases in steady-state IL-8 and MCP-1 mRNA
      expression by 2 h of LPS or cytokine stimulation (rIL-1 beta > fTNF-alpha > LPS >
      rIFN-gamma), maintained at 24 h ELISA for IL-8 and MCP-1 proteins showed
      significant time- and dose-dependent OF secretion after exposure to recombinant
      cytokine or LPS (rIL-1 beta > rTNF-alpha > LPS), measured after 4 h of exposure
      (p < 0.01). This increased in the media over the next 20 h. rIFN-gamma was a
      potent stimulant of OF MCP-1, significant by 2 h (p < 0.05), but only a weak
      stimulant of IL-8 at 24 h. OF secreted IL-8 and MCP-1 in response to LPS and
      proinflammatory cytokines, indicating that these resident cells within the orbit
      have the capacity to actively participate in the initiation and propagation of
      orbital inflammation. Strategies aimed at modulating local mediators may be
      helpful in the management of orbital inflammatory disease.

PMID- 9558670
TI  - The "dural tail sign": not always a meningioma.
AB  - Periorbital masses are often referred to oculoplastic surgeons. We report a 20
      year-old patient presenting with a tender supertemporal mass that on gadolinium
      enhanced magnetic resonance imaging (MRI) demonstrated a prominent dural
      enhancement adjacent to the mass, the so-called "dural tail sign." This sign has
      been reported to be highly specific for a meningioma; however recent literature
      challenges this view. In this case as well, the "dural tail sign" was not
      produced by a meningioma.

PMID- 9558672
TI  - Cystic basal cell carcinoma of the orbit and eyelids.
AB  - When basal cell carcinoma develops cystic change, its clinical and radiological
      features vary, leading to confusion in differential diagnosis We report four
      cases with cystic formation of 62 patients with orbital and adnexal basal cell
      carcinoma encountered during the last 12 years. The salient clinical,
      radiological, and histopathological features of these cases are presented and
      differential diagnosis of large cystic lesions in the orbit is discussed. When
      the basal cell carcinoma develops cystic changes it mimics other orbital cysts,
      including inclusion cysts due to penetrating injury, mucoceles, and necrotic
      metastatic tumors.

PMID- 9558671
TI  - Carcinoma of the male breast metastatic to both orbits.
AB  - We report the case of a 43-year-old man who presented with painless proptosis of
      the right eye of 6 weeks' duration. Examination demonstrated a tense right orbit
      and decreased vision and extraocular motility bilaterally. Diagnostic evaluation
      included computed tomographic imaging of the head and orbits, a therapeutic trial
      of high-dose systemic corticosteroids, and orbital biopsy, which revealed the
      presence of metastatic adenocarcinoma. The primary tumor was found to be an
      estrogen-receptor-positive, infiltrating ductal adenocarcinoma of the right
      breast. Therapy included lumpectomy of the breast mass, orbital irradiation, and
      hormonal therapy. Metastatic carcinoma of the breast should be considered in the
      differential diagnosis of orbital neoplastic disease in the male patient.

PMID- 9558673
TI  - Rounding of the inferior rectus muscle: a helpful radiologic findings in the
      management of orbital floor fractures.
AB  - The authors describe a patient with an orbital floor fracture that did not
      demonstrate a distinct fracture on computed tomography (CT) imaging. The key
      radiologic finding was rounding of the inferior rectus muscle.

PMID- 9558674
TI  - Standardized range of conformers and symblepharon rings.
AB  - Conformers and symblepharon rings are routinely used to keep fornices formed
      after socket surgery or in the presence of conjunctival cicatricial disease.
      However, there is no accepted standard size or shape of conformers or
      symblepharon rings. We measured the ideal conformer and symblepharon sizes in
      patients undergoing socket surgery and designed six conformer and symblepharon
      sizes. The full set of six conformers and symblepharon rings is available to the
      surgeon at the end of surgery. We have successfully used these conformers and
      symblepharon rings in over 600 cases during the last 7 years. These standardized
      sizes allow more accurate fitting of conformers and symblepharon rings.

PMID- 9558675
TI  - Incision site tissue necrosis after dacryocystorhinostomy.
AB  - Incision site tissue necrosis (ISTN) after surgical procedures of the facial area
      is rare. In this article, two patients who have suffered from ISTN after
      dacryocystorhinostomy (DCR) are reported. No known causes have been found for
      this complication; however, over-cauterization could be considered a contributing
      factor in at least one of our cases.

PMID- 9558676
TI  - Primary herniation of the lacrimal gland.

PMID- 9558677
TI  - Pacemaker event counters: possible sources of error in calculation of AV
      synchrony in VDD single lead systems as an example for present limitations.

PMID- 9558678
TI  - Tilt table testing of young adult patients: improved speed and sensitivity using
      an isoproterenol bolus and a continuous 60 degrees tilt.
AB  - The tilt table is a diagnostic device used to induce vagal syncope and determine
      etiology. Sensitivity enhancing techniques, such as the administration of
      isoproterenol, can be applied to children and young adults to compensate for the
      otherwise low sensitivity (20%-30%) observed in that population. This study
      describes an improved test that offers a simplified approach while decreasing the
      amount of time involved by up to 50%, without compromising sensitivity. This 45
      minute procedure relies on sensitization with isoproterenol administered as a 2-
      to 80 micrograms bolus instead of a continuous infusion. The isoproterenol is
      injected at the 30th minute of a 45-minute 60 degrees tilt test without returning
      the patient to the supine position. In this study, the isoproterenol bolus tilt
      test was found to be "positive" in 24 of 30 patients reporting unexplained
      syncope: 10 cases before the 30th minute (11.2 +/- 8.4 min) and 14 cases after
      administration of 5.1 +/- 1.9 micrograms of isoproterenol.

PMID- 9558679
TI  - Subclavian venogram as a guide to lead implantation.
AB  - Recent reports have raised doubts regarding the safety and efficacy of the blind
      subclavian venipuncture technique for intracardiac lead implantation. To permit a
      more lateral entry, we used a simple subclavian venogram performed through the
      brachial vein of the ipsilateral arm of 22 consecutive unselected patients
      undergoing lead implantation (19 permanent pacemakers and 3 intracardiac
      defibrillators). A total of 35 leads were implanted (31 left pectoral and 4 right
      pectoral). Lead insertion by venogram technique was used successfully in all
      patients. Two inconsequential arterial punctures occurred. There were no
      pneumothoraces infections, or other complications. Lateral placement should
      facilitate lead manipulation and minimize "subclavian crush." The method of
      ipsilateral venogram guided lead insertion appears to be safe and reliable and
      deserves consideration in patients who require permanent lead placement via the
      subclavian vein approach.

PMID- 9558680
TI  - "In-line" bipolar, steroid-eluting, high impedance, epimyocardial pacing lead.
AB  - Recent advances in electrode surface designs have eliminated traditional
      threshold differences between endo- and epicardial pacing leads. Since the
      epicardial approach offers the potential of direct left ventricular pacing and
      the transvenous approach may not be feasible or warranted in all instances, more
      advanced leads are being designed to optimize epicardial pacing capabilities.
      This study was conducted to evaluate a bipolar epimyocardial lead. Six immature
      canines (age 3 months) were instrumented. The lead (Medtronic model 10389) is a
      single-pass, "in-line" bipolar electrode with low current drain and high
      impedance, with an intramyocardial steroid-eluting cathode and nonsteroid
      epicardial anode. Twelve ventricular leads were implanted (two per animal) and
      the animals followed for 6 months with weekly analysis of pacing and sensing
      capabilities. Results at explant were compared with implant values and showed no
      significant differences between sensed R waves or in R wave slew rates in
      unipolar or bipolar modes. Explant lead impedances remained high in both modes:
      bipolar, 1658 +/- 331; and unipolar, 1327 +/- 308 omega (P < 0.05). Chronic
      voltage (V) threshold at 0.5 ms showed no significant change from implant values
      during the study: unipolar, 0.3 +/- 0.06 versus 1.0 +/- 0.8; and bipolar, 0.4 +/-
      0.06 versus 1.6 +/- 1.2. Histologic review showed negligible fibrous reaction at
      the electrode-tissue interface. This study introduces a high impedance, low
      threshold, "in-line" bipolar pacing lead design capable of stable chronic pacing
      with implant facilitated by a single suture technique.

PMID- 9558681
TI  - Scoring method for assessing rate adaptive pacemakers: application to two
      different activity sensors.
AB  - To optimize programming of rate adaptive pacemakers (RAPs), we explored a new
      mathematical method to assess the performance of RAPs during daily-life tests,
      using customized Windows-based software. By stepwise discriminant analysis and
      linear regression, this method allows calculation of the acceleration and
      deceleration capacity of pacemakers and their general behavior during effort and
      recovery phases. Twenty-three patients (10 females and 13 males; 68 +/- 8 years)
      with chronic atrial fibrillation and a slow ventricular response were evaluated.
      They randomly received an accelerometer-controlled VVIR Dash Intermedics
      pacemaker (10 patients) or a vibration piezoelectric-controlled VVIR Sensolog III
      Siemens pacemaker (13 patients). All patients underwent the same test protocol: 6
      minutes walking, 1.5 minutes climbing stairs, 1.5 minutes descending stairs, and
      0.5 minutes sit-ups. By definition, the pacemaker responsiveness slope was
      programmed so that the heart rate response of paced patients during the walking
      test corresponded best to that of healthy controls. The slope was left unchanged
      for the other tests. We considered four scores: an acceleration score (EA score),
      an effort rate score (ER score), a deceleration score (RD score), and a recovery
      rate score (RR score). Scores ranged from -10 (hypochronotropic behavior of the
      pacemaker) to +10 (hyperchronotropic behavior), based on daily-life tests of 15
      healthy controls (7 females and 8 males, 65 +/- 9 years). A score of 0
      represented exact concordance with healthy controls. During stair descent, the
      Sensolog III produced excessive acceleration (EA score = +2.9 +/- 1.1) compared
      to: (1) stair climbing (EA score = -4.0 +/- 1.9; P = 0.01, with the same
      pacemakers); and (2) the Dash (+1.8 +/- 1.9; P = 0.04) and healthy controls (P =
      0.02). The sit-up tests revealed a hypochronotropic response of both pacemakers
      compared to healthy controls, with a larger difference for the Sensolog III (EA
      score = -2.0 +/- 5.8; P = 0.04; RD score = -6.8 +/- 3.8' P = 0.02). We conclude
      that activity-driven pacemakers can accommodate brief activities, except for
      isovolumetric exercise such as sit-ups. During daily activities, accelerometer
      driven pacemakers seem to provide a heart rate resoibse closer to that of healthy
      controls. Our new mathematical analysis is a simple and reproducible method for
      evaluating and quantifying the efficacy of any sensor-driven pacemaker.

PMID- 9558682
TI  - Venous dysfunction and the change of blood viscosity during head-up tilt.
AB  - The precise stimulus that induces vasovagal syncope is still unclear. We have
      previously demonstrated that the peripheral distribution of blood volume (venous
      pooling) is a strong predictor of tilt induced vasovagal reaction. We
      hypothesized that an increase in venous pooling during tilt accentuates the
      measured increase in blood viscosity. This hypothesis is based on the previously
      demonstrated increase in venous pressure and subsequent increase in
      transcapillary fluid transudation during tilt. The increased blood viscosity, in
      turn, increases vascular shear rate, which may alter the vasoconstrictive and
      other cardiovascular responses to decreased preload. We measured blood viscosity
      (supine and tilt) in 56 patients with a history of orthostatic intolerance (37
      with venous pooling [VP] and 19 without venous pooling [non-VP]). VP and non-VP
      were separated into subgroups based on blood pressure and heart rate response to
      tilt. There was a positive correlation between blood viscosity and plasma
      aldosterone in the supine. In the group as a whole, neither supine blood
      viscosity nor its increase during tilt differed between VP and non-VP. However,
      the tilt induced increase of blood viscosity was significant only in patients
      with tilt provoked tachycardia plus normal blood pressure response in VP group.
      We suggest that the increase of blood viscosity in this group led to the normal
      blood pressure response. The positive correlation between supine blood viscosity
      and supine plasma aldosterone indicates that the normal blood pressure response
      in this group possibly was via stimulation of the renin-angiotensin-aldosterone
      system.

PMID- 9558683
TI  - Effects of procainamide on the excitable gap composition in common human atrial
      flutter.
AB  - The composition of the excitable gap (EG) in common atrial flutter (AF1) was
      determined before and during infusion of procainamide (PA) in 9 patients (6 men
      and 3 women; age 70 +/- 7 years). The EG was determined by introducing a
      premature stimulus after every 20th AF1 complex detected using a quadripolar
      electrode catheter placed just above the tricuspid valve. Diastole was scanned in
      2- to 4-ms decrements to the atrial effective refractory period (ERP). The
      relationship between the coupling interval and the return cycle length (CL)
      determined a reset-response curve (RRC), which described the EG. PA (15 mg/kg)
      was administered during AF1 over 30 minutes and RRC was repeated at maximum AF1
      CL. PA prolonged AF1 CL from 227 +/- 29 to 296 +/- 62 ms (P < 0.01) but did not
      terminate AF1. ERP during AF1 prolonged from 169 +/- 24 to 219 +/- 41 ms (P <
      0.01). Control EG was 57 +/- 16 ms or 25% +/- 6% of AF1 CL and on PA EG was 77 +/
      30 ms (P = 0.01), which was still 26% +/- 7% of the CL. Without drug, RRC was
      mixed in eight cases demonstrating an EG composed of fully excitable tissue (10
      +/- 4 ms or 19% +/- 10% of the EG) and partially refractory tissue (48 +/- 18
      ms). PA did not change the duration of the fully excitable region (13 +/- 10 ms
      or 19% +/- 15% of EG). Peak PA plasma concentration was 47 +/- 20 mumol/L. PA
      prolonged AF1 CL, ERP, and EG duration but did not change the proportion of AF1
      CL occupied by the EG. The persistance of fully excitable tissue at the head of
      the wavefront in the presence of PA may largely explain its inefficacy in the
      acute termination of common AF1.

PMID- 9558684
TI  - Hemodynamic benefits of right ventricular outflow tract pacing: comparison with
      right ventricular apex pacing.
AB  - To assess optimal hemodynamics in relation to stimulation site during right
      ventricular pacing, 17 consecutive patients who underwent cardiac catheterization
      were studied. In all patients, right ventricular apex and right ventricular
      outflow tract stimulation was performed at 85, 100, and 120 beats/min. Cardiac
      index at both pacing sites was compared using the left ventricular outflow tract
      continuous wave Doppler technique. Comparison of the two stimulation sites
      demonstrated that right ventricular outflow tract pacing resulted in a higher
      cardiac index at 85 beats/min (2.42 +/- 1.2 vs 2.04 +/- 1.0 L/min per m2, P <
      0.002) at 100 beats/min (2.78 +/- 1.4 vs 2.35 +/- 1.1 L/min per m2, P < 0.001)
      and 120 beats/min (3.00 +/- 1.5 vs 2.61 +/- 0.9 L/min per m2, P < 0.001). From a
      total of 51 paired observations, 45 showed an increase in cardiac index during
      outflow tract pacing as compared to apex pacing. Right ventricular outflow tract
      pacing at 120 beats/min resulted in a lower cardiac index than right ventricular
      apex pacing in patients with significant coronary artery disease and/or impaired
      left ventricular function (ejection fraction < or = 50%), whereas right
      ventricular outflow tract pacing produced higher cardiac indices in the absence
      of these abnormalities. Right ventricular outflow tract pacing resulted in higher
      cardiac indices as compared to apex pacing in all other subgroups at all other
      pacing sites tested. It is concluded that stimulation of the right ventricular
      outflow tract offers a significant hemodynamic benefit during single chamber
      pacing as compared to conventional apex pacing, particularly in the absence of
      significant coronary artery disease and/or left ventricular dysfunction.

PMID- 9558685
TI  - Efficacy of ventricular rate stabilization by right ventricular pacing during
      atrial fibrillation.
AB  - To assess the effect of right ventricular pacing on rate regularity during
      exercise and daily life activities, 16 patients with sinoatrial disease and
      chronic atrial fibrillation (AF) were studied. Incremental ventricular pacing was
      commenced at 40 beats/min until > 95% of ventricular pacing were achieved during
      supine, sitting, and standing. Thirteen patients also underwent randomized paired
      submaximal exercise tests in either a fixed rate mode. (VVI) or a ventricular
      rate stabilization (VRS) mode in which the pacing rate was set manually at 10
      beats/min above the average AF rate during the last minute of each exercise
      stage. The pacing interval for rate regularization was shortest during standing
      (692 +/- 26 ms) compared with either supine or sitting (757 +/- 30 and 705 +/- 26
      ms, respectively, P < 0.05). During exercise VRS pacing significantly increased
      the maximum rate (119 +/- 5.2 vs 106 +/- 4.2 ms, P < 0.05), percent of
      ventricular pacing (85% +/- 5% vs 23% +/- 7%, P < 0.05), rate regularity index
      (5.8% +/- 1.6% vs 13.4% +/- 1.9%, P < 0.05), and maximum level of oxygen
      consumption (12.4 +/- 0.5 vs 11.3 +/- 0.5 mL/kg, P < 0.05) compared with VVI
      pacing. There was no change in oxygen pulse or difference in symptom scores in
      this acute study between the two pacing modes. It is concluded that right
      ventricular pacing may significantly improve rate regularity and cardiopulmonary
      performance in patients with chronic AF. This may be incorporated in a pacing
      device for rate regularization of AF using an algorithm that is rate adaptive to
      postural and exercise stresses.

PMID- 9558686
TI  - Experience with a lead fixation/suture sleeve.
AB  - Current anchoring systems on pacemaker leads are crude in comparison to the lead
      technology. Poor anchoring technique may cause damage to the lead or early
      displacement from incorrect suture tension. We describe experience with a locking
      anchoring sleeve that applies a constant gripping force to the lead body. This
      can be locked and unlocked to allow optimal positioning after fixation of the
      sleeve to underlying tissues. The sleeve was fitted to a 55D polyurethane lead
      (Medtronic 4024, 7 Fr, bipolar, steroid eluting) implanted in the ventricular
      position in 22 patients at four European centers. All implants were
      uncomplicated; data were collected on handling and ease of use. Assessments were
      made using a scale of 1-10 (10 = excellent, 5 = equivalent to conventional
      sleeve). Overall ease of use compared to conventional sleeve was 7.79 +/- 0.62
      (mean +/- SD). Mean scoring of flexibility of the lead at the transition points
      was 7.92 +/- 0.72; ability to lock/unlock the sleeve scored 6.28 +/- 1.78. Ease
      of suturing around the sleeve scored 8.07 +/- 0.77, and ability to slide the
      sleeve along the lead body scored 6.48 +/- 1.99. Chest X rays at 6 weeks showed
      no change in lead position with respect to postimplant films, and all leads
      showed a straight path on either side of the sleeve with no evidence of conductor
      distortion. Follow-up to 3 years has been without problem. All leads remain
      intact and in place, with stable thresholds and no evidence of erosion. There
      have been no complaints of patient discomfort. We conclude that this device is
      safe and effective and offers a significant advance in lead fixation.

PMID- 9558687
TI  - Thoracoscopic radiofrequency ablation of the myocardium.
AB  - Radiofrequency (RF) catheter ablation has been used for the treatment of
      ventricular tachycardia (VT), however, in some patients VT might result from
      subepicardial macroreentry that could be successfully terminated by epicardial
      approach. This study examined the feasibility of thoracoscopic RF ablation of
      myocardium from epicardium using a custom made electrode. In five mongrel dogs,
      the thoracoscope was introduced through the 7th intercostal space. A 500-KHz
      continuous wave RF energy was connected to a custom made multiple electrode
      probe. Under thoracoscopic guidance, the heart was exposed and the RF probe was
      introduced. RF ablation was performed on the nonvascular ventricular wall of the
      beating heart. The left ventricular free wall and right ventricular outflow tract
      were satisfactorily visualized and ablated. The total dose of RF energy ranged
      from 50 to 500 J, and the estimated volume of ablated lesions ranged from 41.0
      799 mm3. There were significant correlations between the RF discharge output and
      the irradiated lesion volume (P < 0.01), and the depth of the lesions (P < 0.01).
      Grossly, after RF ablation the ventricular myocardium demonstrated a circular,
      well-demarcated area of thermal injury. Volume and depth of the lesion depended
      upon the total dose of delivered RF energy. Thoracoscopic RF ablation appears to
      be a minimally invasive and useful method for creating irradiated myocardial
      lesions from epicardial surface. This method could be technically feasible for
      the treatment of Vts for which endocardial RF ablation is ineffective.

PMID- 9558689
TI  - Cardiac rehabilitation in patients with rate responsive pacemakers.
AB  - This study investigated the suitability of our oxygen pulse reserve (OPR) method
      for tailoring parameters of rate responsive pacemakers and planning aerobic
      rehabilitation programs. We selected 11 patients, NYHA Classes I-III (7 males and
      4 females; mean age 60 years, range 18-83), with rate responsive pacemakers
      implanted for high degree AV block and chronotropic incompetence. Five pacemakers
      had activity sensors, 4 had temperature sensors, and 2 had dual sensors. All
      patients underwent a cardiopulmonary stress test (CPX). We determined anaerobic
      threshold time (ATT), VO2/AT, total exercise time (TET), VO2 Max, and VO2 AT/VO2
      Max. OPR (mL-O2/beat) was calculated for each patient using the formula OPR =
      (VO2 Max - VO2 resting)/(HR Max - HR resting). During CPX, this slope was used as
      the rate response tailoring guideline by comparing the mL-O2/beat equation and
      the pacing rate. Rate response settings were modified until the optimal
      relationship between theoretical and paced rate was obtained. The work protocol
      yielded rate response settings capable of providing pacing rates within +/- 10
      beats of the theoretical values. Data relating to theoretical and measured rates
      have been analyzed statistically. Patients underwent an aerobic rehabilitation
      program that followed the American College of Sports Medicine guidelines. Pacing
      rate at the anaerobic threshold was considered the border for an aerobic
      workload. After 2-7 months, all patients showed an evident improvement in ATT
      (92%), VO2/AT (48%), TET (49%), VO2 Max (23%), and VO2 AT/VO2 (21%).
      Particularly, two patients improved from Weber Class C to A, and three improved
      from C to B. At each CPX step, the mean values of pacing rate and theoretical
      rate almost overlap, and the relevant coefficients suggest an excellent
      correlation (P < 0.001). Our OPR method for tailoring rate response provides the
      basis for an effective rehabilitation program with functional advantages for
      patients.

PMID- 9558688
TI  - Effects of hydrophilic and lipophilic beta-blockers on heart rate variability and
      baroreflex sensitivity in normal subjects.
AB  - To evaluate the effect of a hydrophilic and a lipophilic beta-blocker on the
      autonomic nervous system, 20 normal subjects were studied under baseline
      conditions and 7 days after being randomly assigned to metoprolol (200 mg/day),
      nadolol (80 mg/day), and placebo. Under each condition, the time-domain
      parameters were analyzed by means of 24-hour ECG monitoring and the frequency
      domain parameters by means of the autoregressive method using 10-minute ECGs
      during rest, controlled respiration, and after a head-up tilt test. The alpha
      index (the gain in the relationship between the RR period and systolic arterial
      pressure variability) was also calculated. Both nadolol and metoprolol
      significantly increased all of the time-domain parameters except the standard
      deviation of the RH intervals; they also modified the frequency-domain
      parameters. Both blunted the significant reduction in the high frequency (HF)
      component and alpha index during tilt. In normal subjects, hydrophilic and
      lipophilic beta-blockers similarly modify the time- and frequency-domain
      parameters that are particularly evident when high sympathetic tone is present
      (during daytime and tilt). The value of the alpha index was increased by both
      beta-blockers in the HF, but not in the low frequency band; this difference might
      be due to the fact that the former is a measure of the vagal component of the
      baroreflex control and the latter a measure of the sympathetic component. The
      effects of hydrophilic and lipophilic beta-blockers on the time- and frequency
      domain parameters of heart rate variability are similar.

PMID- 9558690
TI  - JT dispersion in Wolff-Parkinson-White syndrome: effect of eccentric ventricular
      depolarization on the dispersion of repolarization.
AB  - There is much interest in QT dispersion for noninvasive risk stratification of
      patients at risk of arrhythmias. However, little is known about the genesis of
      abnormal QT dispersion. In particular, whether eccentric ventricular
      depolarization, as seen in preexcitation, can lead to abnormal dispersion of
      repolarization is unknown. We studied 24 children aged 1-19 years (mean +/- SD,
      11 +/- 5 years) with manifest preexcitation due to Wolff-Parkinson-White syndrome
      who had successful catheter ablation. Standard ECGs done preablation, early
      postablation (< 1 week), mid postablation (> 1 week, < 2 months), and late
      postablation (> 2 months) were reviewed. The QRS duration prior to ablation
      ranged from 90-160 ms (mean +/- SD, 123 +/- 21 ms). On the preablation ECG, the
      JT and JTc dispersions showed no relationship to the QRS duration (r = 0.04 and
      0.07, respectively). There was no change in JT dispersion when the preablation
      (42 +/- 15 ms) ECG was compared to early (43 +/- 15 ms), mid (44 +/- 13 ms), and
      late postablation (48 +/- 19 ms) ECGs. There was no significant change in JTc
      dispersion as well. Thus, JT dispersion is unrelated to QRS duration and
      unaffected by catheter ablation in patients with Wolff-Parkinson-White syndrome.
      Eccentric ventricular depolarization does not lead to abnormal dispersion of
      repolarization.

PMID- 9558691
TI  - Transvenous single lead atrial defibrillation: efficacy and risk of ventricular
      fibrillation in an ischemic canine model.
AB  - Transvenous atrial defibrillation with multiple atrial lead systems has been
      shown to be effective in models without the potential for ventricular
      arrhythmias. The specific aim of this study was to evaluate the efficacy and
      safety of transvenous single lead atrial defibrillation in a canine model of
      ischemic cardiomyopathy. Ten dogs had ischemic cardiomyopathy induced by repeated
      intracoronary microsphere injections. The mean LV ejection fraction decreased
      from 71% +/- 9% to 38% +/- 14% (P = 0.003). Spontaneous atrial fibrillation (AF)
      developed in four dogs, and in six AF was induced electrically. Atrial
      defibrillation thresholds (ADFTs) were determined with synchronous low energy
      shocks using a transvenous tripolar lead with two defibrillation coils (right
      ventricle, superior vena cava) and an integrated sensing lead (RV coil vs
      electrode tip). The ADFTs derived by logistic regression were compared at 50% and
      90% probability of success (ED50, ED90): ED50 was 2.4 +/- 1.7 J and 2.9 +/- 2.1
      J, respectively, for 5- and 10-ms monophasic shocks, and 1.8 +/- 0.9 J,
      respectively, for 5- and 10-ms biphasic shocks. Immediately after 3 of 2,179
      (0.1%) synchronized shocks, ventricular fibrillation (VF) developed. VF was
      induced in 3 of 1,062 (0.3%) shocks with integrated sensing (RV coil vs electrode
      tip) compared to 0 of 1,117 shocks when a separate bipolar RV sensing electrode
      was used for synchronization. In our canine model of ischemic cardiomyopathy, low
      energy atrial defibrillation via a transvenous single lead system was highly
      effective. However, there was a small but definite risk of VF induction, which
      seemed to be greater when an integrated as opposed to a true bipolar RV sensing
      was used.

PMID- 9558692
TI  - Rhythm management in atrial fibrillation--with a primary emphasis on
      pharmacological therapy: Part 1.
AB  - Atrial fibrillation (AF) is the most common, sustained, symptomatic
      tachyarrhythmia that clinicians are called upon to manage. Management strategies
      include ventricular rate control coupled with anticoagulation, versus restoration
      and maintenance of sinus rhythm. Rate control may be achieved pharmacologically,
      with agents that impair AV nodal conduction directly and/or by increasing
      parasympathetic/sympathetic balance, or by modifying or ablating the AV nodal
      region anatomically. Rhythm control may be achieved by electrical or
      pharmacological conversion followed by maintenance of sinus rhythm by
      pharmacological (or occasionally ablative) therapies. This article will present
      current approaches to rate and rhythm control issues in AF. Part 1, the current
      manuscript, details approaches to rate control and includes a drug selection
      algorithmic conclusion. It also introduces the subject of the pursuit of sinus
      rhythm. Parts 2 and 3, to be published in subsequent editions of PACE, will deal
      with therapeutic measures to restore and maintain sinus rhythm.

PMID- 9558693
TI  - Stepwise strategy on the cost of risk stratification after acute myocardial
      infarction: a retrospective simulation study.
AB  - Stratification of postinfarction patients at high risk of mortality and/or other
      adverse events can be improved by combining several prognostic markers. As the
      clinical impact of risk stratification has only recently emerged in prospective
      trials, there are a lack of data regarding the cost-effectiveness of multimarker
      strategies. This study performed a comprehensive search of a postinfarction
      database and simulated different risk stratification strategies involving left
      ventricular ejection fraction, signal-averaged electrocardiography, Holter
      monitoring, and heart rate variability, The parameters were assessed before
      discharge in 417 survivors of acute myocardial infarction followed-up for 1 year.
      Cardiac mortality was used as the clinical endpoint. A statistical computer model
      of a stepwise strategy using every feasible sequence of the four tests was used
      and, based on prices derived from European and American centers, the cost
      estimates of all possible combinations were compared. During the 1 year after
      myocardial infarction there were 24 cardiac deaths (5.8%). In all the population,
      6% had all four tests positive (cardiac mortality 20%); 25% had at least three
      tests positive (cardiac mortality 12.5%); 58% had at least two tests positive
      (cardiac mortality 8.3%); and 92% presented with at least one test positive
      (cardiac mortality 6.3%). The cost of performing all the tests ranged between
      $398 and $1,887 for each patient. However, by selecting patients according to a
      step wise strategy, the costs ranged from $96 (> or = 1 test positive) to $510
      (for the least expensive sequences of four tests positive). For each of the
      centers considered, the costs resulting from the risk stratification protocol
      were determined by the number of variables combined and sequences of tests
      adopted. Thus, a step wise strategy using the combination of all four parameters,
      starting with analysis of Holter variables and finishing with signal-averaged
      electrocardiography, appears to be the most appropriate and the least expensive
      approach for selecting patients at high risk of cardiac death.

PMID- 9558694
TI  - FDA reform: new law to impact EP and pacing services at home and abroad.

PMID- 9558695
TI  - Possible involvement of cerebral hypoperfusion as trigger of neurally-mediated
      vasovagal syncope.
AB  - It is well known that some patients with neurally mediated syncope have a feeling
      of aura before the onset of syncope. A case is reported in which cerebral
      dysfunction recorded by EEG was present before the onset of a vasovagal reaction.
      The vasovagal reaction, bradycardia and/or asystole, was preceded by abnormal EEG
      findings when the patient complained of feeling a headache, photophobia, and
      nausea. These findings suggest that cerebral hypoperfusion, such as with cerebral
      vasospasms, before the onset of bradycardia might be involved in the mechanism of
      neurally mediated syncope in patients with an aura.

PMID- 9558696
TI  - Accidental entry of an implantable cardioverter defibrillator lead into the left
      hepatic vein detected by transesophageal echocardiography.
AB  - We report a case of accidental entry of an implantable cardioverter defibrillator
      lead into the hepatic vein, which was not noted on fluoroscopy but was apparent
      when transesophageal echocardiography (TEE) was used incidentally. The lead was
      depicted in the hepatic vein as strongly echogenic, accompanied by an acoustic
      shadow. Additional bending of the stylet was helpful for successful advancement
      of the lead. TEE provides additional information in such cases, although
      indications for its use should be explored because of its possible complications.

PMID- 9558697
TI  - Transcoronary ethanol ablation of the atrioventricular node in a young patient
      with tricuspid atresia.
AB  - Catheter ablation of AV conduction with radiofrequency energy can be challenging
      in the presence of structural abnormalities of the AV junction, either
      congenitally or after reconstructive surgery. We used transcoronary ethanol to
      ablate the AV node in a patient with classic tricuspid atresia and refractory
      intraatrial reentry tachycardia. This approach provides an alternative means of
      creating complete heart block with catheter-based techniques, when radiofrequency
      catheter ablation is technically impossible or ineffective.

PMID- 9558698
TI  - Lipoinjection as a treatment of pacemaker pocket neuralgia.
AB  - Chronic severe pacemaker pocket neuralgia secondary to inadequate subcutaneous
      tissue between the pacemaker and overlying skin typically is treated by surgical
      pocket revision or relocation of the system. A case of this complication
      successfully treated by lipoinjection is reported. Additional experience is
      needed to confirm the usefulness of the technique as a means of providing
      symptomatic relief without the risks associated with more invasive procedures.

PMID- 9558699
TI  - Reposition of an implantable cardioverter defibrillator generator from an
      abdominal pocket to a subpectoral location using the existing electrode.
AB  - The size of today's implantable cardioverter defibrillator generators makes a
      subpectoral position feasible even when an existing generator is located
      abdominally. Elective replacement with reposition of the generator from an
      abdominal to a subpectoral pocket without implantation of another electrode is
      described.

PMID- 9558701
TI  - 11 patients in whom atrial fibrillation was converted by a right atrial electrode
      and a left pectoral patch.

PMID- 9558700
TI  - Cerebral embolism due to a retained pacemaker lead: a case report.
AB  - There are only a few reported cases of a pacemaker lead migrating inadvertently
      into the left atrium or ventricle. An unusual complication of unremoved, unwanted
      pacemaker lead is presented. The free tip of the lead caused cerebral embolism
      after perforating the interatrial septum.

PMID- 9558702
TI  - [How myosin works].

PMID- 9558703
TI  - [The influence of myosin light chains and their function].

PMID- 9558705
TI  - [Proteoglycans--structure and functions].

PMID- 9558704
TI  - [Myotonic dystrophy--dynamic mutation and disease pathogenesis].

PMID- 9558706
TI  - [Obesity genes].

PMID- 9558707
TI  - [Bacterial transcription termination].

PMID- 9558708
TI  - [CpG islands--the only unmethylated fragments of DNA in the vertebrate genome].

PMID- 9558709
TI  - [Metabolism of phosphorylated derivatives of 8-oxo-2'-deoxyguanosine].

PMID- 9558710
TI  - [Capillary electrophoresis: a new tool for biomolecule separation].

PMID- 9558711
TI  - Stable isotope methodology for kinetic studies of interconversion of cortisol and
      cortisone in a human subject.
AB  - Oral administration of 5 mg each of deuterium-labeled cortisol ([1,1,19,19,19
      2H5]cortisol, cortisol-d5) and cortisone-d5 ([1,1,19,19,19-2H5]cortisone) to a
      human subject on two different occasions four weeks apart provided a useful means
      of characterizing the kinetics of the interconversion of cortisol and cortisone.
      From the data on plasma concentration measurements of cortisol-d5, cortisone-d5,
      cortisone-5, endogenous cortisol and endogenous cortisone by gas chromatography
      mass spectrometry, it was demonstrated that (1) the plasma concentration ratio of
      cortisone-d5 to cortisol-d5 approached a plateau 4-5 h following either the
      cortisol-d5 or cortisone-d5 administration and the plateau values for the
      cortisone-d5 and cortisol-d5 administration were almost identical (about 0.43)
      and (2) dosing with only 5 mg of the deuterium-labeled steroids suppressed the
      plasma concentrations of endogenous cortisol and cortisone.

PMID- 9558712
TI  - Synthesis of 6 beta-aminoestradiol and its biotin, acridinium, and fluorescein
      conjugates.
AB  - Amination of 3,17 beta-Bis[(2-trimethylsilylethoxy) methoxy]-1,3,5(10)
      estratriene-6-one (2) using NaCNBH4 and NH4OAc afforded 3,17-bis(SEM)-6
      aminoestradiol (3) as a mixture of alpha and beta-isomers in 60:40 ratio.
      Hydrolysis of the mixture of 3 using HF and separation by preparative high
      performance liquid chromatography afforded pure 6 beta-aminoestradiol (4) in good
      yield. The relative stereochemistry of the amino group in 4 was established by
      NMR. The biotinylated estradiol probe (7), chemiluminescent probe (9), and
      fluorescent probe (11), were prepared from 6 beta-aminoestradiol (4) and the
      corresponding biotin, 10-(3-sulfopropyl)-N-tosyl-N-(3-carboxypropyl)acridinium-9
      carboxamide, and 5-carboxyfluorescein N-succinimidyl esters in 43-63% yields and
      > 99% purity.

PMID- 9558713
TI  - An unusual dienone-phenol rearrangement product formed during the synthesis of
      mometasone furoate (Sch 32088).
AB  - The structure of an unusual dienone-phenol rearrangement product 4 obtained
      during the synthesis of mometasone furoate (Sch 32088) was assigned on the basis
      of NMR and x-ray crystallographic data. The mechanism of formation is discussed.

PMID- 9558714
TI  - Synthesis of new immunogens for estrone and estradiol-17 beta and antisera
      evaluation.
AB  - Syntheses of the 6 alpha-O-carboxymethyl ether derivatives of estrone and
      estradiol-17 beta and the preparation of their bovine serum albumin conjugates
      are described. The generation and evaluation of antisera produced from these
      conjugates is discussed.

PMID- 9558715
TI  - DNA polymorphism in B-domain of the estrogen receptor-alpha among Japanese women.
AB  - A silent mutation in B-domain of the estrogen receptor-alpha (ER B) change codon
      87 (from GCG to GCC) is clinically correlated with frequent spontaneous abortion
      and familial history of breast cancer among Caucasian patients. However, none of
      the 167 Japanese female patients and 46 Japanese female healthy volunteers showed
      ER B variant. Therefore, this DNA polymorphism might involve a genetic racial
      difference, and appears not to be correlated with frequent spontaneous abortion
      or familial history of breast cancer at least among Japanese women.

PMID- 9558717
TI  - Ergosteroids. II: Biologically active metabolites and synthetic derivatives of
      dehydroepiandrosterone.
AB  - An improved procedure for the synthesis of 3 beta-hydroxyandrost-5-ene-7,17
      dione, a natural metabolite of dehydroepiandrosterone (DHEA) is described. The
      synthesis and magnetic resonance spectra of several other related steroids are
      presented. Feeding dehydroepiandrosterone to rats induces enhanced formation of
      several liver enzymes among which are mitochondrial sn-glycerol 3-phosphate
      dehydrogenase (GPDH) and cytosolic malic enzyme. The induction of these two
      enzymes, that complete a thermogenic system in rat liver, was used as an assay to
      search for derivatives of DHEA that might be more active than the parent steroid.
      Activity is retained in steroids that are reduced to the corresponding 17 beta
      hydroxy derivative, or hydroxylated at 7 alpha or 7 beta, and is considerably
      enhanced when the 17-hydroxy or 17-carbonyl steroid is converted to the 7-oxo
      derivative. Several derivatives of DHEA did not induce the thermogenic enzymes
      whereas the corresponding 7-oxo compounds did. Both short and long chain acyl
      esters of DHEA and of 7-oxo-DHEA are active inducers of the liver enzymes when
      fed to rats. 7-Oxo-DHEA-3-sulfate is as active as 7-oxo-DHEA or its 3-acetyl
      ester, whereas DHEA-3-sulfate is much less active than DHEA. Among many steroids
      tested, those possessing a carbonyl group at position 3, a methyl group at 7, a
      hydroxyl group at positions 1, 2, 4, 11, or 19, or a saturated B ring, with or
      without a 4-5 double bond, were inactive.

PMID- 9558716
TI  - Estrogen-dependent gene regulation by an oxidative metabolite of
      diethylstilbestrol, diethylstilbestrol-4',4"-quinone.
AB  - Diethylstilbestrol (DES) is a well-characterized carcinogen in humans and animals
      although its mechanisms of carcinogenicity are not yet known. While the
      estrogenic activity of DES is important, there is evidence that oxidative
      metabolism also plays an important role for its toxicity. DES is oxidatively
      metabolized in vivo and in vitro to a number of compounds including
      diethylstilbestrol-4',4"-quinone (DQ), an unstable and reactive intermediate, and
      Z,Z-dienestrol (ZZ-DIEN). Estrogen receptor (ER) binding assays with mouse
      uterine cytosol indicate that DES, DQ and ZZ-DIEN have relative binding
      affinities of 286, 3.6 and 0.3, respectively, relative to estradiol as 100. In
      addition, DQ binds irreversibly and specifically to ER suggesting that DQ may be
      biologically active despite its rapid metabolism and lower binding affinity
      compared to DES. To test this, COS-1 cells were transfected with an estrogen
      responsive reporter construct containing of VitA2 estrogen response element (ERE)
      with or without an ER expression vector. In the presence of ER, treatments with
      DES, DQ and ZZ-DIEN resulted in 11, 10, and 2-fold induction of chloramphenicol
      acetyltransferase (CAT) activity, respectively. This induction was mediated by
      estrogen receptor since it was suppressed by pretreatment with a 10-fold excess
      of the pure antiestrogen ICI 182,780. These data indicate that DQ is a
      biologically active intermediate that is capable of transactivation of estrogen
      responsive genes through the ER. Furthermore, the data suggest that the ability
      of DQ to irreversibly bind ER may result in persistent stimulation of ER. This
      persistent stimulation may be related to the carcinogenicity of DES.

PMID- 9558718
TI  - Synthesis and biological activity of 11,19-bridged progestins.
AB  - A synthetic approach to 11,19-bridged progestins is described. The key step in
      the synthesis is a 6-endo-trig radical cyclisation. The new progestins were
      tested for their biological activities in vitro and in vivo and compared to those
      of known progestins.

PMID- 9558719
TI  - Integrating advanced laparoscopy into surgical residency training. Society of
      American Gastrointestinal Endoscopic Surgeons (SAGES).
AB  - SAGES was founded to further the advancement of surgeons performing
      gastrointestinal endoscopy. In part due to the society's previous efforts,
      training in flexible endoscopy is now recognized as a mandatory component of
      training in general surgery. SAGES has more recently promoted the safe practice
      of laparoscopic surgery, which since 1991 has evolved to be a standard component
      of the practice of most general surgeons. Consistent with the goal of continuing
      to provide the public with surgeons competent in performing all varieties of
      appropriate laparoscopic procedures, SAGES joins other major surgical
      organizations in addressing the concern that, while basic laparoscopic procedures
      are mastered during residency training in general surgery, advanced procedures
      and the skills required to initiate safely an experience in them often are not.
      Incorporation of advanced laparoscopic surgical skills into surgical residency
      and the safe incorporation and performance of advanced laparoscopic operations
      into surgical practice are dynamic processes. With the above proposals, SAGES
      hopes to facilitate both processes. We have, herein, set forth suggested
      curriculum guidelines for resident training in laparoscopic surgery. We have
      outlined measures by which resident and faculty training in advanced laparoscopic
      surgical skills may be realized. Focusing on adequately training the trainers is
      essential in order to facilitate residency training in the future. As practice
      patterns evolve and the frequency of laparoscopic operations increases, the
      opportunities for residents to learn required skills will increase. As a result,
      they will be able to accomplish safely such procedures. In that setting, the
      proposed special efforts outlined above may no longer be necessary.

PMID- 9558720
TI  - Guidelines for granting of privileges for laparoscopic and/or thoracoscopic
      general surgery. Society of American Gastrointestinal Endoscopic Surgeons
      (SAGES).

PMID- 9558721
TI  - Granting of privileges for gastrointestinal endoscopy by surgeons. Society of
      American Gastrointestinal Endoscopic Surgeons (SAGES).

PMID- 9558722
TI  - Obesity after genetic ablation of brown adipose tissue.
AB  - Brown adipose tissue (BAT) has been proposed to play an important role in the
      regulation of energy balance. The unique presence of uncoupling protein (UCP)
      permits BAT to expend calories unrelated to the performance of work with the net
      result being the generation of heat. The role of BAT in mediating diet-induced
      thermogenesis had led to the suggestion that BAT activity contributes to
      metabolic inefficiency and, as such, might provide a cellular and molecular
      explanation for protection from obesity. In order to directly test this
      hypothesis, we recently created mice with isolated BAT deficiency by using a
      suicide DNA transgenic vector in which regulatory elements of the UCP gene were
      used to drive brown fat specific expression of diptheria toxin A-chain (DTA).
      Transgenic mice are characterized by reduced energy expenditure and marked
      obesity, associated with insulin resistance and NIDDM with both receptor and post
      receptor components. Feeding of a "Western diet" which derives 41% of its
      calories from fat leads to a synergistic effect on the development of obesity and
      its accompanying disorders in transgenics. The results of our studies support a
      critical role for BAT in the nutritional homeostasis of mice and suggest that the
      intact thermogenic function of BAT is required for protection from diet induced
      obesity. Obese UCP-DTA mice have many features in common with obesity as it
      appears in most humans, and should therefore be a useful model that may aid
      studies of the pathogenesis and treatment of human obesity, NIDDM and their
      complications.

PMID- 9558723
TI  - Nutritional and hormonal regulation of the gene for malic enzyme.
AB  - In vivo, refeeding starved chickens stimulates transcription of the avian gene
      for malic enzyme in liver; in hepatocytes in culture, triiodothyronine (T3) and
      insulin stimulate transcription of this gene. In vivo, starvation, and in
      hepatocytes in culture, glucagon, medium-chain fatty acids (MCFA) and long-chain
      fatty acids (LCFA) inhibit transcription of the malic enzyme gene. We have
      defined a T3-response unit in the 5'-flanking DNA of the malic enzyme gene; it
      contains one major T3 response element and several minor ones; maximum
      responsiveness is dependent on the presence of all of these elements. LCFA
      probably act by inhibiting binding of T3 to its nuclear receptor. MCFA appear to
      act by a different mechanism. Inhibitory MCFA have chain lengths of six, seven or
      eight carbons; a common feature of other inhibitory compounds is that they can be
      metabolized to MCFA. Eight-carbon fatty acids with a hydroxyl on the 2- or 3
      carbon are more potent inhibitors than octanoate, whereas 2-bromo-fatty acids and
      2-hydroxy hexanoate are not inhibitory. In transfection experiments with a large
      variety of constructs derived from the malic enzyme 5'-flanking DNA, the ability
      of fatty acids to inhibit promoter function localizes to regions of DNA that
      contain T3REs. Promoter function of artificial T3REs also is inhibited by MCFA.
      Inhibition of promoter function using malic enzyme DNA is relatively constant in
      magnitude irrespective of the size of the T3 response. We postulate that MCFA
      directly regulates one of the functions of the T3 receptor.

PMID- 9558724
TI  - Polyunsaturated fatty acid inhibition of fatty acid synthase transcription is
      independent of PPAR activation.
AB  - Polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families inhibit the
      rate of gene transcription for a number of hepatic lipogenic and glycolytic
      genes, e.g., fatty acid synthase (FAS). In contrast, saturated and
      monounsaturated fatty acids have no inhibitory capability. The suppression of
      gene transcription resulting from the addition of PUFA to a high carbohydrate
      diet: occurs quickly (< 3 h) after its addition to a high glucose diet; can be
      recreated with hepatocytes cultured in a serum-free medium containing insulin and
      glucocorticoids; can be demonstrated in diabetic rats fed fructose; and is
      independent of glucagon. While the nature of the intracellular PUFA inhibitor is
      unclear, it appears that delta-6 desaturation is a required step in the process.
      Recently, the fatty acid activated nuclear factor, peroxisome-proliferator
      activated receptor (PPAR) was suggested to be the PUFA-response factor. However,
      the potent PPAR activators ETYA and Wy-14643 did not suppress hepatic expression
      of FAS, but did induce the PPAR-responsive gene, acyl-CoA oxidase (AOX).
      Similarly, treating rat hepatocytes with 20:4 (n-6) suppressed FAS expression but
      had no effect on AOX. Thus, it appears that the PUFA regulation of gene
      transcription involves a PUFA-response factor that is independent from PPAR.

PMID- 9558725
TI  - RRR-alpha-tocopherol regulation of gene transcription in response to the cell
      oxidant status.
AB  - RRR-alpha-Tocopherol, but not RRR-beta-tocopherol, negative regulates
      proliferation of vascular smooth muscle cells at physiological concentrations. At
      the same concentrations RRR-alpha-tocopherol inhibits protein kinase C activity,
      whereas RRR-beta-tocopherol is ineffective. Furthermore, RRR-beta-tocopherol
      prevents the inhibition of cell growth and of protein kinase C activity caused by
      RRR-alpha-tocopherol. The negative regulation by RRR-alpha-tocopherol of protein
      kinase C activity appears to be the cause of smooth muscle cell growth
      inhibition. RRR-alpha-Tocopherol does not act by binding to protein kinase C
      directly but presumably by preventing protein kinase C activation. A second RRR
      alpha-tocopherol effect has been found at the level of AP 1, the latter becoming
      activated by RRR-alpha-tocopherol under condition of protein kinase C inhibition
      or down regulation. AP-1 inhibition by RRR-alpha-tocopherol is seen, however,
      under condition of protein kinase C stimulation. Compositional changes of AP-1
      have been found to be at the basis of the RRR-alpha-tocopherol effects. RRR-beta
      tocopherol, provided with similar antioxidant properties, not only it does not
      affect AP 1 but it prevents the effects of RRR-alpha-tocopherol. Moreover, it has
      been observed that RRR-alpha-tocopherol is able to affect TRE regulated gene
      transcription. It is concluded that RRR-alpha-tocopherol acts specifically in
      vascular smooth muscle cells, by controlling a signal transduction pathway
      leading to cell proliferation by a non-antioxidant mechanism.

PMID- 9558726
TI  - Effects of retinoids on gene expression in different epithelial models in vivo
      and in vitro.
AB  - We have previously reported that the induction of Vitamin A deficiency results in
      a threefold decrease in the hepatic expression of cellular retinol binding
      protein I (CRBP I) mRNA in vivo and that the treatment of intestinal cell lines
      in vitro with retinoids leads to the induction of CRBP I transcription. In the
      present paper we extend the analysis to retinoid-dependent gene expression in the
      testicular epithelium in vivo and in the intestinal cell line FRIC B. In rat
      testis excess Vitamin A results in the reduced production of mature spermatozoa
      and in the premature release of immature germ cells in the lumen, while Vitamin A
      deficiency leads to almost complete degeneration of the germinal epithelium. We
      show reduced level of expression of CRBP I mRNA in vitamin A deficient testis.
      Retinoid treatment of cultured intestinal cells, which induces a reorganization
      of the actin cytoskeleton, has no effect on the expression of the differentiation
      induced gene Dri 42. The results show that even though unable to trigger by
      themselves the differentiation process, retinoids exert a direct effect on the
      expression of specific genes.

PMID- 9558727
TI  - Antioxidant modulation of cytokines and their biologic function in the aged.
AB  - The oxidant/antioxidant balance is an important determinant of immune cell
      function, including maintaining integrity and functionality of membrane lipids,
      cellular proteins, nucleic acids, and for control of signal transduction and gene
      expression in immune cells. Optimal levels of antioxidants are needed for
      maintenance of the immune response across all age groups. This need might be more
      critical, however, in the aged. Age-associated dysregulation of immune response,
      particularly of cytokine production and T-cell-mediated function, is well
      documented. The well-known age-related increase in free radical formation and
      lipid peroxidation contributes, at least in part, to this phenomenon. This review
      will summarize animal and human studies undertaken by the authors as well as
      those by other investigators on the effect of antioxidants, vitamin E, beta
      carotene, and glutathione on cytokine production and T-cell-mediated function in
      the aged.

PMID- 9558728
TI  - Interleukin-6 and related cytokines: effect on the acute phase reaction.
AB  - The acute phase response is the answer of the organism to disturbances of its
      physiological homeostasis. It consists of a local and a systemic reaction. The
      latter is characterized by dramatic changes in the concentration of some plasma
      proteins called acute phase proteins. Interleukin-6 (IL-6) has been identified in
      vitro and in vivo as the major hepatocyte stimulating factor. Subsequently,
      additional hepatocyte stimulating factors, such as leukemia inhibitory factor,
      oncostatin-M, interleukin-11 and ciliary neurotrophic factor have been
      discovered. IL-t and related cytokines belong to the so-called alpha-helical
      cytokine family characterized by four antiparallel helices. IL-6 and IL-6-type
      cytokines exert their action via plasma membrane receptor complexes consisting of
      specific cytokine binding subunits and a common signal transducing protein gp130.
      In this presentation we focus on structure/function studies of IL-6, its receptor
      subunits gp80 and gp130, the internalization of the ligand/receptor complex and a
      recently elucidated signal transduction pathway. We have shown that protein
      tyrosine kinases of the JAK family are associated with the cytoplasmic domain of
      gp130 and are activated in response to IL-6. Subsequently, the transcription
      factors--named STATs (signal transducers and activators of transcription)--STAT1
      alpha and STAT3 are transiently recruited to the cytoplasmic domain of gp130,
      where they become tyrosine phosphorylated by JAK kinases. In addition to the
      tyrosine phosphorylation we have observed that IL-6 also induces a serine
      phosphorylation of STAT3. This modification occurs with a delayed time-course as
      compared to the tyrosine phosphorylation and is inhibited by the protein kinase
      inhibitor H7. We propose that the STAT3 serine phosphorylation is required for
      transactivation of IL-6 target genes which is also inhibited by H7.

PMID- 9558729
TI  - Selenium and immune function.
AB  - Selenium (Se), an essential nutrient required for optimal growth of mammalian
      cells, affects the immune functions of a host in vivo. Utilizing a mouse model
      system and healthy human volunteers, we have shown that Se enhances the capacity
      of lymphocytes to respond to stimulation with mitogen or alloantigen, to
      proliferate, and to differentiate into cytotoxic effector cells. Supplementation
      with Se resulted in a significant increase in the tumor cytotoxicity of mouse
      cytotoxic lymphocytes, lymphokine activated killer cells and macrophages, and
      human cytotoxic lymphocytes and natural killer (NK) cells. Se also appears to
      abrogate the age-related deficiency of lymphocytes from an aged host to respond
      to stimulation by proliferation and differentiation into cytotoxic effector
      cells. These effects occurred in the absence of changes in the endogenous levels
      of interleukin-1, interleukin-2, or interferon-gamma, and were related to the
      ability of Se to enhance the expression of the alpha (p55) and/or beta (p70/75)
      subunits of the interleukin-2 receptor (IL-2R) on the surface of activated
      lymphocytes and NK cells. This resulted in a greater number of functional IL
      2R/cell and in enhanced proliferation and clonal expansion of cytotoxic precursor
      cells. The molecular mechanism that mediates the effects of Se on immune cell
      function does not appear to be related to the function of Se as an antioxidant or
      to gene activation.

PMID- 9558730
TI  - Modulation of pro-inflammatory cytokine biology by unsaturated fatty acids.
AB  - The production of pro-inflammatory cytokines, such as interleukins 1 and 6 and
      tumour necrosis factors, occurs rapidly following trauma or invasion of the body
      by pathogenic organisms. The cytokines mediate the wide range of symptoms
      associated with trauma and infection, such as fever, anorexia, tissue wasting,
      acute phase protein production and immunomodulation. In part, the symptoms result
      from a co-ordinated response, in which the immune system is activated and
      nutrients released, from endogenous sources, to provide substrate for the immune
      system. Although the cytokine mediated response is an essential part of the
      response to trauma and infection, excessive production of pro-inflammatory
      cytokines, or production of cytokines in the wrong biological context, are
      associated with mortality and pathology in a wide range of diseases, such as
      malaria, sepsis, rheumatoid arthritis, inflammatory bowel disease, cancer and
      AIDS. Cytokine biology can be modulated by antiinflammatory drugs, recombinant
      cytokine receptor antagonists and nutrients. Among the nutrients, fats have a
      large potential for modulating cytokine biology. A number of trials have
      demonstrated the anti-inflammatory effects of fish oils, which are rich in n-3
      polyunsaturated fatty acids, in rheumatoid arthritis, inflammatory bowel disease,
      psoriasis and asthma. Animal studies, conducted by ourselves and others, indicate
      that a range of fats can modulate pro-inflammatory cytokine production and
      actions. In summary fats rich in n-6 polyunsaturated fatty acids enhance IL1
      production and tissue responsiveness to cytokines, fats rich in n-3
      polyunsaturated fatty acids have the opposite effect, monounsaturated fatty acids
      decrease tissue responsiveness to cytokines and IL6 production is enhanced by
      total unsaturated fatty acid intake. There are a large number of potential
      cellular mechanisms which may mediate the effects observed. The majority relate
      to the ability of fats to alter the composition of membrane phospholipids. As a
      consequence of alterations in phospholipid composition, membrane fluidity may
      change, altering binding of cytokines to receptors and G protein activity. The
      nature of substrate for various signalling pathways associated with cytokine
      production and actions may also be changed. Consequently, alterations in
      eicosanoid production and activation of protein kinase C may occur. We have
      examined a number of these potential mechanisms in peritoneal macrophages of rats
      fed fats with a wide range of fatty acid composition. We have found that the
      total C18:2 and 20:4 diacyl species of phosphatidylethanolamine in peritoneal
      macrophages relates in a positive curvilinear fashion with dietary linoleic acid
      intake; that TNF induced IL1 and IL6 production relate in a positive curvilinear
      fashion to linoleic acid intake; that leukotriene B4 production relates
      positively with dietary linoleic acid intake over a range of moderate intakes and
      is suppressed at high intakes, while PGE2 production is enhanced. There was no
      clear relationship between linoleic acid intake and membrane fluidity, however
      fluidity was influenced in a complex manner by the type of fat in the diet, the
      period over which the fat was fed and the presence of absence of TNF stimulation.
      None of the proposed mechanisms, acting alone, can explain the positive effect of
      dietary linoleic acid intake on pro-inflammatory cytokine production. However
      each may be involved, in part, in the modulatory effects observed.

PMID- 9558731
TI  - Beneficial effects of cytokine induced hyperlipidemia.
AB  - Infection, inflammation and trauma induce marked changes in the plasma levels of
      a wide variety of proteins (acute phase response), and these changes are mediated
      by cytokines. The acute phase response is thought to be beneficial to the host.
      The host's response to injury also results in dramatic alterations in lipid
      metabolism and circulating lipoprotein levels which are mediated by cytokines. A
      large number of cytokines including TNF, the interleukins, and the interferons
      increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly
      due to an increase in hepatic VLDL secretion while the late increase may be due
      to a variety of factors including increased hepatic production of VLDL or delayed
      clearance secondary to a decrease in lipoprotein lipase activity and/or
      apolipoprotein E levels on VLDL. In animals other than primates, cytokines also
      increase serum cholesterol levels, most likely by increasing hepatic cholesterol.
      Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase
      gene expression and decrease hepatic cholesterol catabolism by inhibiting
      cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury
      and/or cytokines also decrease HDL cholesterol levels and induce alterations in
      the composition of HDL. The content of SAA and apolipoprotein J increase,
      apolipoprotein A1 may decrease, and the cholesterol ester content decreases while
      free cholesterol increases. Additionally, key proteins involved in HDL metabolism
      are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels
      decrease. These changes in lipid and lipoprotein metabolism may be beneficial in
      a number of ways including: lipoproteins competing with viruses for cellular
      receptors, apolipoproteins neutralizing viruses, lipoproteins binding and
      targeting parasites for destruction, apolipoproteins lysing parasites,
      redistribution of nutrients to cells involved in the immune response and/or
      tissue repair, and lipoproteins binding toxic agents and neutralizing their
      harmful effects. Thus, cytokines induce marked changes in lipid metabolism that
      lead to hyperlipidemia which represents part of the innate immune response and
      may be beneficial to the host.

PMID- 9558732
TI  - Localization of somatostatin receptor subtype mRNA in the rat gastrointestinal
      tract and regulation of SSTR1 gene expression.
AB  - Somatostatin and its receptors are widely distributed in the central nervous
      system and peripheral tissues including those of the gastrointestinal tract (GI
      tract). The expression patterns of the five known SSTR genes have been analysed
      in detail by reverse transcription polymerase chain reaction amplifications and
      in situ hybridizations using tissues dissected from different parts of rat
      stomach and gut. While SSTR1 mRNA is present at relatively high amounts
      throughout the gastrointestinal tract, the levels of SSTR2, 3 and 4 mRNAs vary in
      different regions and SSTR5 mRNA has not been detected. In situ hybridizations
      revealed the presence of SSTR3 mRNA in enterocytes and in neurons of the
      myenteric and submucous plexus. These findings are consistent with a role of
      SSTR3 in the observed somatostatin-mediated inhibition of acetylcholine release
      from myenteric neurons and of secretomotor neuron activity in the submucous
      plexus. Sequence analyses of the SSTR1 gene promoter revealed the absence of the
      canonical TATA and CAAT motifs and the presence of a variety of potential binding
      sites for transcriptional regulators. Among these are binding sites for GCF, AP
      2, AP-4, response elements for somatostatin (SOM-RE), epidermal growth factor
      (EGF-RE) and cytocines (GAS and NFIL) as well as for tissue-specific factors such
      as Pit-1 (pituitary) and IDX-1 (pancreatic cells). Mobility shift assays have
      confirmed that nuclear proteins of pancreatic RIN1046-38 and pituitary GH3 tumour
      cells bind to oligonucleotides containing the overlapping Pit-1 and IDX-1 binding
      sites. Thus, the Pit-1/IDX-1 sites may be critical for the activation of the
      SSTR1 gene in these cell-types.

PMID- 9558733
TI  - Potential influence of increased sub-lethal UV-A irradiation on aquatic food
      production (Aquaculture).
AB  - In the tropics organisms have permanently adapted to deal with extremely high
      intensities of light, temperature and other environmental factors. Especially in
      coastal environments and fish farmings conditions can easily reach and exceed the
      tolerance limits of an organism. The UV-A band has been shown to be a potent
      modulator of light induced effects and general physiological functions in
      organisms. The biological endpoints and underlying mechanisms still have to be
      investigated. Our experiments were carried out with the easy to handle sub
      tropical Convict-Cichlid fish (Cichlasoma nigrofasciatum) as a model organism. In
      our studies we observed that constant sub-lethal UV-A irradiation had a
      significant effect on the general metabolism and on the sensitivity towards other
      environmental stress factors in this fish. We found that, in addition to the
      depression of the general metabolism, sub-lethal UV-A irradiation in combination
      with elevated environmental temperature had a deleterious effect on the
      population. The threshold temperature for a sudden increase in mortality of the
      fish receiving the additional sub-lethal UV-A irradiation was 32 degree C. The
      fish were grown and adapted at 27-29 degrees C. A total of 78% of the fish
      receiving an additional UV-A irradiation died by high temperature stress while
      the reference population remained at a normal level (3%). The metabolic rate (MR)
      of the UV-A survivors during temperature stress was less than half the average
      value obtained in the reference population. After the environmental temperature
      returned below the apparent upper tolerance limit for this fish, the MR of UV-A
      population gradually increased to normal. Apparently a constant elevated sub
      lethal dose of UV-A leads to the destabilization of an organism, making it more
      sensitive for other environmental stress factors. These observations seem to be
      important considerations in fish farming in the tropical and subtropical regions.

PMID- 9558734
TI  - Regulation of the LDL receptor gene expression by hormones.
AB  - Promoter activity of the LDL receptor gene is stimulated by insulin and estradiol
      and mediated by SRE-1, which acts as a hormone sensitive cis-elemente. Using the
      antisense technique we reveal that SREBP-1 is selectively involved in the signal
      transduction pathway of insulin and IGF-I.

PMID- 9558735
TI  - Influence of dietary fiber on DNA adduct formation in rat tissues.
AB  - The occurrence of DNA-adduct-like indigenous compounds (I-compounds) was examined
      in tissue samples of rats differing in their microbial state and diet with or
      without pectins of different degrees of esterification (DE). For 21 days groups
      of six germfree and ten conventional rats were each fed either pectin-free or
      with diets containing 7.5% of three differently esterified pectin preparations
      (pectin A: DE 92.6%; pectin B: DE 70.8%; pectin C: DE 34.5%). DNA was isolated
      from colonic mucosa, liver, lung, kidney and measured by the highly sensitive 32P
      postlabelling assay for DNA adduct analysis. In germfree animals I-compounds were
      detected in all tissue samples after feeding the low-esterified pectin C. Under
      the higher-esterified pectins, A and B, a weak adduct formation could be
      demonstrated only in the liver, but not in the colonic mucosa, lung, and kidney.
      In conventional animals DNA adducts were found in all samples of colonic mucosa
      with the highest intensity in the control group, followed by the low-esterified
      pectin C group, and a weak intensity under the higher-esterified pectins A and B.
      The experiments show a tendency to a higher number and intensity of spots in the
      germfree compared with the conventional rats, in rats with a pectin-free compared
      with the pectin diet, and under the low-esterified compared with the higher
      esterified pectins.

PMID- 9558736
TI  - Pathobiochemical effects of graded magnesium deficiency in rats.
AB  - Severe Mg deficiency changed mineral homeostasis, induced membrane damage,
      increased lipid peroxidation and cytokine concentrations, and reduced
      immunocompetence. In order to investigate whether the pathobiochemical effects
      correlate directly with the degree of Mg deficiency or whether there might be a
      threshold with no detectable effects above, diets with 70, 110, 208, 330 and 850
      ppm Mg were fed to growing Wistar rats. After feeding the diets for 0, 10, 20 and
      30 days parameters of free radical action (malondialdehyde and vitamin E
      content), mineral content (Mg, Ca, Fe) in various tissues (liver, spleen, heart,
      kidney, muscle) and plasma parameters (Mg, Ca, Fe, alanine- and aspartate
      aminotransferase) were measured. After 30 days 6-keto-prostaglandin F1 alpha,
      thromboxane B2, tumor necrosis factor-alpha, and immunoglobulins (IgG, IgM, IgA)
      were additionally analyzed. Tissue Mg content was either unchanged or only
      slightly reduced in severe Mg deficiency. Tissue Fe content rose when the
      extracellular Mg concentration was below 0.25 mM. There was a close positive
      correlation between tissue Fe and malondialdehyde content, and malondialdehyde
      was negatively correlated with vitamin E content. Below a threshold of about 0.25
      mM plasma Mg concentration, transaminases increased in plasma. The same threshold
      could be observed for the increase of tissue Ca content, except in the kidney
      where calcifications were found already in mild Mg deficiency. Tumor necrosis
      factor-alpha and 6-keto-prostaglandin F1 alpha were increased when the plasma Mg
      concentration was below 0.15 mM, and thromboxane B2 was increased when plasma was
      lower than 0.25 mM. IgG and IgA were significantly reduced below 0.25 mM plasma
      Mg and IgM below 0.4 mM plasma Mg. Mild Mg deficiency, therefore, can be
      compensated and might not lead to pathological symptoms if not combined with
      other pathobiological conditions.

PMID- 9558737
TI  - Cosinor analysis of circadian oscillations of amino acid catabolizing enzymes in
      temporal pattern of nutrient input.
AB  - Circadian oscillations of liver tyrosine aminotransferase (TAT) tryptophan
      oxygenase (TO), alanine aminotransferase (ALAT), aspartate aminotransferase
      (ASAT), and glutamate dehydrogenase (GLDH) in temporal pattern of protein input
      have been investigated. Cosinor analysis of oscillations parameters revealed the
      glucocorticoid induction of TO activity and protein induction of TAT activity
      rhythm. ALAT, ASAT, and GLDH activities showed 24 h fluctuations, but the
      regulation mechanisms remain unclear.

PMID- 9558738
TI  - Anti-gliadin and anti-endomysium antibodies in children with celiac disease
      consuming a gluten free diet.
AB  - A group of 26 children (13 boys and 13 girls; average age 12.2 years) with CD who
      had been on a gluten free diet for 5-15 years was examined in order to find out
      how effectively they could manage their diet. The diagnosis of CD was established
      on the basis of ESPGAN criteria (1969). 5-15 years ago. Antigliadin antibodies,
      IgG-, and IgA-AGA (by fluorescence enzyme immunoassay), Gliastick by ELISA
      technique, and Anti-endomysium antibodies (by indirect immunofluorescence on
      sections of monkey esophagus) were examined in the serum. Only 5 patients had no
      antigliadin or anti-endomysium antibodies. In 21 cases the IgG-AGA showed
      positive results; the IgA-AGA was positive in 6, the Gliastick in 19, and the
      anti-endomysium antibodies in 8 cases. The main cause of the mismanagement of the
      diet was inadequate food labeling; so it seems to be important to also establish
      a Food Intolerance Data Bank in Hungary. The 5 sero-negative children volunteered
      for a gluten challenge; 3 of them became positive in a few weeks or months. Two
      patients remained negative even after 1 year. Their gluten sensitivity may not
      prove to be permanent.

PMID- 9558740
TI  - Attempt to differentiate between individual glutathione peroxidases in biological
      samples.
AB  - Routine determinations of glutathione peroxidases (GPx) still suffer from poor
      standardization and usually from lack of specification. The different types of
      glutathione peroxidases present in cellular homogenates may be differentially
      estimated by their distinct substrate specificities. Complex lipid hydroperoxides
      required for this approach, however, are not generally available nor easily
      standardized due to their molecular heterogeneity and tendency to form micelles.
      We therefore developed a simple procedure for the differential estimation of the
      major cellular types of GPx, the cytosolic GPx (cGPx) and the phospholipid
      hydroperoxide glutathione peroxidase (PHGPx) taking advantage of the peculiar
      susceptibility of PHGPx to deoxycholate. It proved to reliably determine the
      activities of both purified cGPx and PHGPx, in mixtures thereof, and in
      homogenates of tissue samples (e.g., testes), and some (e.g. ECV 304) but not all
      (e.g. THP-1) cultured cell lines. The method allows the differential estimation
      of cGPx and PHGPx, if the samples do not contain further types of GPx.

PMID- 9558739
TI  - Parenteral selenium supplementation in critically ill patients--effects on
      antioxidant metabolism.
AB  - Decreased plasma selenium (Se) levels are common in critically ill patients.
      Oxidative stress is regarded as one possible cause of the Se deficiency. We
      investigated in 20 critically ill patients with decreased plasma selenium
      concentrations the antioxidant metabolism during parenteral selenium
      supplementation (week 1: 2 x 500 micrograms; week 2:1 x 500 micrograms, week 3:3
      x 100 micrograms sodium selenite). As marker of oxidative stress we measured the
      plasma malondialdehyde levels on days 0, 1, 3, 7, 14, and 21. The content of
      reduced and oxidized glutathione as well as the leucocyte activity marker
      elastase were estimated on the same days. Initial plasma Se levels were
      considerably decreased (0.44 +/- 0.1 mumol/l, mean +/- SEM). After one day of
      supplementation Se concentrations were in the reference range. Plasma
      malondialdehyde levels and the ratio of oxidized and reduced glutathione were
      initially elevated and decreased beginning on day 3 of supplementation. The mean
      elastase level was 113 +/- 10 micrograms/l on day 0. On day 3 elastase values
      decreased significantly (85 +/- 13 micrograms/l, p < 0.05; day 21, 19 +/- 7
      micrograms/l, p < 0.001). Antioxidant metabolism showed significant changes
      beginning after 72 hours of therapy. This latency may be explained with the
      induction of the enzyme glutathione peroxidase. The lowered plasma Se
      concentrations measured in the critically ill patients and the significant
      effects on antioxidant metabolism during supplementation emphasized the
      importance of selenium administration in these patients.

PMID- 9558741
TI  - Test system for quantification of stop codon suppression by selenocysteine
      insertion in mammalian cell lines.
AB  - A convenient test system was designed to investigate the efficiencies of
      selenocysteine inserting sequences (SECIS) responsible for the cotranslational
      incorporation of selenocysteine into selenoproteins of mammals. It comprises an
      expression vector in which the lacZ and luc genes are separated by an in-frame
      TGA stop codon. The coding regions are followed by a multicloning region allowing
      exchange of putative SECIS elements. Stop codon suppression associated with
      selenocysteine incorporation is readily estimated on the basis of relative
      luciferase activity measurements, thus providing a measure of SECIS efficiency.

PMID- 9558742
TI  - Probing the presumed catalytic triad of a selenium-containing peroxidase by
      mutational analysis.
AB  - Glutathione peroxidases (GPx) are characterized by a catalytically active
      selenium which forms the center of a strictly conserved triad composed of
      selenocysteine, glutamine, and tryptophan. In order to check the functional
      relevance of this structural peculiarity, six molecular mutants of phospholipid
      hydroperoxide glutathione peroxidase (PHGPx) were designed, isolated, and
      investigated kinetically. Replacement of the selenocysteine in position 46 by
      cysteine decreased k + 1, i.e., the reaction rate of reduced enzyme with
      hydroperoxide, by three orders of magnitude. The rate of regeneration of the
      reduced enzyme by glutathione (k' + 2) was similarly affected. Additional
      substitution of Gln81 or Trp136 by acid residues resulted in a further decrease
      of k + 1 by three orders of magnitude, whereas histidine or neutral residues in
      these positions proved to be less deleterious. The data support the hypothesis
      that the typical triad of selenocysteine, glutamine, and tryptophan is indeed a
      novel catalytic center in which the reactivity of selenium is optimized by
      hydrogen bonding provided by the adjacent glutamine and tryptophan residues.

PMID- 9558743
TI  - Plasma arachidonic acid and serum thromboxane B2 concentrations in
      phenylketonuric children are correlated with dietary compliance.
AB  - Phenylketonurics display lower arachidonic acid levels in plasma lipids,
      reflecting the lower intake due to the dietary treatment poor in phenylalanine
      rich animal foods. Plasma arachidonic acid levels and serum thromboxane B2
      concentrations have been measured in 13 treated phenylketonuric children and
      compared with those of 12 healthy controls. A direct relationship between plasma
      arachidonic acid and thromboxane B2 concentrations has been observed only in
      phenylketonurics, whose plasma arachidonic acid status correlated negatively with
      their dietary compliance. These results suggest that the low consumption of
      animal fats may contribute to modulate the production of arachidonic acid-derived
      platelet eicosanoids.

PMID- 9558745
TI  - Fruit: comparisons of attitudes knowledge and preferences of primary school
      children in England and Germany.
AB  - Primary school children's fruit consumption and attitudes, knowledge and
      preferences towards fruit were investigated using interview techniques in schools
      in England (Nottinghamshire) and Germany (North East) and analysed on the basis
      of culture, sex and social class. Children from both countries had strong
      positive attitudes to increase fruit consumption and differed little in their
      ability to correctly identify five fruits (including tropical fruits). Fruit
      preferences also showed many similarities with more than 95% of children from
      both Germany and England choosing apples as fruits they liked, followed closely
      by strawberries, oranges, pears, grapes, and bananas. Fruit consumption by German
      children was, however, higher than English children both at breakfast and during
      the school break. Strategies for increasing fruit consumption in English children
      are discussed in relation to the findings obtained.

PMID- 9558744
TI  - Clinical application of the polyunsaturated n-3 fatty acids usage in pediatric
      practice.
AB  - The investigation of the effectiveness of a diet supplemented with n-3 PUFA in
      children with glomerulonephritis was done. Patients receiving "Polyen" achieved
      better clinical remission, more rapid decrease of hypercholesterolemia, and
      hypercoagulation than the patients from the control group. We can recommend
      "Polyen" usage in the treatment of glomerulonephritis in children.

PMID- 9558746
TI  - Lipid status in adolescents born with low birth weight.
AB  - The study compared anthropometric parameters and lipid status of adolescent boys
      and girls (14-16 y) born with LBW or ABW. Values for body weight and height of
      LBW adolescents were lower than those for ABW's. BMI differed significantly
      between LBW and ABW boys. In LBW boys, serum LDL-C level was somewhat lower, and
      the ApoA1 concentration was higher than in ABW's. Other lipid parameters did not
      differ among the corresponding groups. These data suggest that
      hypercholesterolemia, which is seen in LBW adults, must develop in older ages,
      and the irregular lifestyle including improper nutritional habits may promote its
      occurrence in this vulnerable group.

PMID- 9558747
TI  - Some data on the prevalence of obesity in Hungarian adult population between 1985
      88 and 1992-94.

PMID- 9558748
TI  - Study of nutritional behavior in a group of Lithuanian men.
AB  - Nutritional status of men, aged 50, which is considered as a high risk group for
      noncommunicable heart diseases was investigated. The study showed that the
      chemical composition of diet could be considered as a risk factor for
      cardiovascular diseases. This diet is too rich in simple sugars and fats,
      especially of animal origin, and poor in complex sugars and antioxidants.

PMID- 9558749
TI  - Effect of dietary fish oil on fecal bile acid and neutral sterol excretion in
      healthy volunteers.
AB  - Diet-induced increases in fecal excretion of secondary bile acids (deoxy- and
      lithocholic acid) and certain neutral sterols (4-cholesten-3-one and 5a-cholestan
      3-one) play a role in colon cancer development, whereas dietary fish oil (FO) has
      been implicated as a protective agent. In the present study the effects of FO and
      corn oil (CO) on these fecal parameters were investigated in 12 healthy
      volunteers consuming a low fat (30% of energy) controlled basal diet. After 4
      weeks of FO supplementation (4.4 g omega-3 fatty acids/day), daily excretion of
      lithocholic acid showed a trend to lower values compared to CO consumption (p =
      0.2), whereas other bile acids were not different during both study periods.
      Daily excretion of the putative colon carcinogen 4-cholesten-3-one was
      significantly lower in the FO compared to the CO period. This may be another
      biochemical mechanism by which FO exerts its protective effect on colon cancer
      development.

PMID- 9558750
TI  - The changes of lymphocyte membrane receptors in bronchial asthma and atopic
      dermatitis in pediatric patients receiving treatment with polyenic fatty acids.
AB  - The influence of a diet supplemented with n-3 PUFA on the immune status of
      children with atopic dermatitis and asthma was investigated. The results of the
      investigation have shown the improvement of cell immunity along with a decrease
      in the clinical manifestation of the disease. n-3 PUFA could be used as
      immunocorrectors in combination with pathogenic treatment of children with
      allergic diseases.

PMID- 9558751
TI  - Coexistence of multiple periodic and chaotic regimes in biochemical oscillations
      with phase shifts.
AB  - The numerical study of a glycolytic model formed by a system of three delay
      differential equations reveals a multiplicity of stable coexisting states:
      birhythmicity, trirhythmicity, hard excitation and quasiperiodic with chaotic
      regimes. For different initial functions in the phase space one may observe the
      coexistence of two different quasiperiodic motions, the existence of a stable
      steady state with a stable torus, and the existence of a strange attractor with
      different stable regimes (chaos with torus, chaos with bursting motion, and chaos
      with different periodic regimes). For a single range of the control parameter
      values our system may exhibit different bifurcation diagrams: in one case a
      Feigenbaum route to chaos coexists with a finite number of successive periodic
      bifurcations, in other conditions it is possible to observe the coexistence of
      two quasiperiodicity routes to chaos. These studies were obtained both at
      constant input flux and under forcing conditions.

PMID- 9558752
TI  - Do MTS have the function of message transmission?
AB  - Structurally, microtubules (MTs) are composed of protofilaments of the subunit
      protein. They are prominent components of the cytoplasmic matrix and perform
      important functions as cytoskeletal elements for the determination of cell shape
      and as key elements in intracellular motility such as mitosis and the
      translocation of cell organelles. These functions are thought to depend on the
      controlled assembly and disassembly of MTs in the cytoplasm and on the
      interaction of MTs with each other and with other cytoplasmic components. I think
      that apart from these cellular functions. MTs have the function of message
      transmission. Although no direct evidence is available to explain this point at
      present, a number of indirect evidences have been obtained by many scientists
      e.g.: brain tissue has circumstantial the highest tubulin concentration, MTs have
      the property of self-assembly and disassembly, microtubule(MT) network is a key
      factor in differentiation of plant cells.

PMID- 9558753
TI  - Community perception on OPD performance of a teaching hospital in Gondar town.
AB  - Among 2605 heads of households interviewed in Gondar Town, 1,099 (42%) had
      visited the Out Patient Department of the Gondar College of Medical Sciences
      Hospital during the past one year. Of these, 856 (78%) were dissatisfied with the
      services. The pharmacy was perceived as the worst unit of the Department. Among
      the 1,042 visitors who had gone to the pharmacy, 76% were unable to buy all the
      drugs prescribed by the physicians. The outcome of treatment as perceived by the
      visitors were 671 (61%) improved and 71 (7%) died at home after seeking
      consultation at the OPD. Mechanisms of improving hospital performances such as
      greater community participation and improved management system are suggested.

PMID- 9558754
TI  - Persistent diarrhoea: socio-demographic and clinical profile of 264 children seen
      at a referral hospital in Addis Ababa.
AB  - Acute diarrhoea is a major public health problem in Ethiopian children under five
      years of age. Reports for other developing countries indicate that persistent
      diarrhoea is emerging as an important cause of mortality and morbidity in this
      age group. Little is, however, known about the extent of the condition in our
      setting. The socio-demographic and clinical characteristics of children with
      persistent diarrhoea seen at a teaching hospital in Addis Ababa over an 18-month
      period is presented. Of 5,762 children with all forms of diarrhoea seen during
      the study period 264 (5%) had persistent diarrhoea. Most of the children (83%)
      were below 18 months of age and the peak occurrence was between the ages of seven
      and 12 months. The majority (86%) of the patients had associated malnutrition and
      83% of the infants under four months of age were either fully or partially
      weaned. Watery diarrhoea with no dehydration was the main clinical feature.
      Nearly 7% of the patients had dysentery. Average family income was low and
      parental literacy level seem to have had no effect. It is suggested that
      breastfeeding and appropriate weaning practices be strongly promoted. Further
      work is proposed in order to determine the magnitude of the problem and identify
      the risk factors associated with the disease, including the unfavourable child
      and family unit characteristics and care seeking behaviours.

PMID- 9558755
TI  - Neonatal sepsis in Addis Ababa, Ethiopia: a review of 151 bacteremic neonates.
AB  - A retrospective study of 542 neonatal sepsis cases was undertaken. Bacteremia was
      confirmed in 151 cases. There were a total of 195 (36%) deaths. Fifty nine (39%)
      of the deaths were from the bacteremia cases. The incidence of sepsis was 11 per
      1000 live births. Klebsiella was the leading etiologic agent (38%), with a
      mortality rate of 54%. Low birth weight was found to be a predisposing factor for
      the development of sepsis and mortality. The high incidence of sepsis, the
      increase in mortality rate and the spread of nosocomial infection is discussed.

PMID- 9558756
TI  - Klebsiella oxytoca outbreak at the Ethio-Swedish Children's Hospital (ESCH).
AB  - Klebsiella oxytoca outbreak at the Ethio-Swedish Children's Hospital, is
      described. The organism was isolated for the first time on Oct. 1992 at the
      emergency room and subsequently spread to all wards including the neonatal unit
      of the hospital. The isolates were resistant to Ampicillin, Amoxicillin,
      Chloramphenicol, Co-trimoxazole and Gentamicin, but sensitive to Amikacin and
      ceftriaxone. Eighty six percent (182) of the isolates were from blood specimen.
      Nine out of ten suspected intravenous infusion bags were positive for Klebsiella
      oxytoca. The source of this nosocomial infection and possible control measures
      are discussed.

PMID- 9558757
TI  - AIDS related knowledge and behaviours among college students, Gondar, Ethiopia: a
      comparative study.
AB  - AIDS-related knowledge and behaviours among students at the Gondar College of
      Medical Sciences, Gondar, Ethiopia were evaluated based on identical surveys
      conducted in 1990 and 1992. One hundred three second year students provided
      information in 1992. Analysis indicated that 49% were engaged in sexual
      intercourse and only a third of these group used condom despite their improved
      knowledge and belief on condom compared to their previous position in 1990 (p <
      0.004). On the other hand, their sexual behaviours regarding sexual contact with
      high risk individuals decreased compared to 1990 (p < 0.0005). Their general
      level of AIDS-related preventive knowledge increased over time (p < 0.002),
      although there was no significant difference in knowledge observed among
      different sexes and departments. Among the sexually active, a large proportion of
      students (22%) still had sexual contact with high risk individuals and only 33%
      of them were using safer methods. Continuing efforts, including peer education,
      specific health education interventions are still crucially needed to bring a
      positive change in sexual behaviour.

PMID- 9558758
TI  - Behcets' disease: a case report.
AB  - A 20 year old male patient presented with recurrent panuveitis associated with
      painful buccal and genital ulcers, subcutaneous nodules and pustules
      (dermatographia) on the trunk, and positive pathergy (skin hypersensitivity to
      needle pricks) test. Laboratory examinations were nonrevealing except for a
      minimal rise in ESR. This patient meets the criteria set by James and Spiteri for
      Bechets' Disease. This disease and its prognosis is discussed. Early recognition
      and treatment of this blinding and potentially fatal disorder is emphasised.

PMID- 9558759
TI  - The importance of the maxillary sinuses in facial development: a case report.
AB  - A case of mandibular asymmetry is presented. It appears that in this patient the
      mandible was adapted to changes in the maxillary sinus area. Abnormal bone growth
      of unknown aetiology inside the sinus most likely caused complete remodelling in
      the maxillary sinuses and asymmetry of the mandible. Special tests used for
      detailed assessment of the patient supported the definitive diagnosis.

PMID- 9558760
TI  - Treatment changes in Class I and mild Class II malocclusions using the en masse
      removable appliance.
AB  - The aim of this retrospective study was to examine the dental changes which
      occurred during buccal segment retraction in 39 subjects considered suitable for
      treatment with headgear to the maxillary dentition. Initially, a removable en
      masse appliance was fitted to distalize the buccal segments. Once the molar
      relationship was corrected, fixed appliances were placed for upper arch
      consolidation and/or alignment. Only five subjects required lower appliance
      therapy. Twenty-nine individuals had upper second molars extracted as an adjunct
      to treatment: in the remaining 10 patients these teeth were left in situ.
      Corresponding lower second molars were extracted in 19 children, whilst 20 pairs
      of teeth were not removed. Measurements were made at the start of treatment, the
      completion of buccal segment retraction, and when active treatment was complete.
      After the first stage, molars and premolars had been retracted nearly 4 mm,
      whilst the canines showed 2 mm spontaneous distal drift. The inter-molar width
      had increased by 4 mm and arch perimeter by 5 mm. There was a 5 per cent
      reduction in crowding. Spontaneous changes were also seen in the lower arch,
      despite the absence of any therapy. Crowding was slightly improved and inter
      molar width increased, apparently as a response to the expansion in the opposing
      jaw. At the end of treatment, upper arch retraction and expansion were reduced as
      the teeth were integrated with the lower dentition: the canines required less
      than 1 mm further retraction. In the lower arch, the expansion of the molars was
      essentially stable. The extraction of upper second molars did not appear to
      influence the outcome of treatment. Although slightly more movement appeared to
      occur in the extraction group, few measurements showed statistical significance.

PMID- 9558761
TI  - Dental changes in the mandible during initial Bass appliance therapy.
AB  - The aim of this study was to analyse movements of lower molars and incisors
      during 6 months of Bass appliance therapy and to evaluate the dental arch space
      attained. The sample consisted of 53 patients with severe Class II, division 1
      malocclusions. The analyses were performed on lateral cephalograms and dental
      casts. Sixteen of the patients were followed for 6 months before treatment.
      Dental space in the lower jaw decreased 0.7 mm (n = 16) during the observation
      period and increased 1.8 mm (n = 53) during the 6 months of treatment. The molars
      moved posteriorly a total of 0.7 and tipped distally 2.4 degrees during
      treatment. The incisors moved anteriorly 0.3 mm and tipped mesially 0.5 degree.

PMID- 9558762
TI  - Soft and hard tissue changes in Class III patients treated by bimaxillary
      surgery.
AB  - A cephalometric study of 17 non-growing dentate Class III subjects treated by
      bimaxillary surgery was undertaken to assess the results of treatment and to
      evaluate the correlation between soft and hard tissue change. It was concluded
      that: (i) the orthognathic profiles achieved were brought about by a combination
      of maxillary advancement and mandibular setback; (ii) a strong correlation in the
      horizontal direction occurred between all the selected landmarks of the lower lip
      and chin, but only between superior labial sulcus and point A in the upper lip;
      highest intra-group correlations were seen between corresponding soft and hard
      tissue points; the ratios of soft tissue to corresponding hard tissue movements
      in lower lip and chin approached 1:1; (iii) in the vertical direction, a strong
      correlation occurred in the lower lip and chin; highest intra-group correlations
      were not necessarily with corresponding landmarks; and (iv) vertical movement of
      landmarks on the nasal base and upper lip generally showed poor or weak
      correlation with corresponding soft tissue points. The most reliable hard tissue
      predictors of horizontal and vertical soft tissue change are tabulated for
      application in bimaxillary surgery for the Class III patient.

PMID- 9558763
TI  - A proportional analysis of some facial height and depth variables in 10 to 16
      year old children.
AB  - A method for analysing the horizontal and vertical proportions of the face is
      described, based on natural head orientation (NHO). It demonstrates how
      individual deviations from the mean proportions can be quantified both
      horizontally and vertically. Correlation between facial depth to height (index 1)
      and the mandibular plane angle was determined and found to be fairly strong and
      highly significant (r = 0.5, P < 0.001). Facial depth to height and lower facial
      height to total facial height (index 2) relationships were found to be strongly
      correlated at each age between 10 and 16 years, with only small mean differences.
      For this reason the norm values presented for 12-year-old children for indices 1
      and 2 should be applicable to orthodontic patients within this age range. The
      relationship between mandible and maxilla (index 3) increases continually between
      10 and 16 years in boys, and between 10 and 14 years in girls, about 0.3 units a
      year. It can provide supplementary information for individual case analysis. For
      boys the increase was 2.2 units per year between 14 and 16 years of age.

PMID- 9558764
TI  - Eruption of premolars subsequent to autotransplantation. A longitudinal
      radiographic study.
AB  - One-hundred-and-eighteen premolars transplanted at a stage with 3/4 to 4/4 root
      development with an open apical foramen were followed using a standardized
      clinical and radiographic technique for signs of periodontal ligament healing,
      root development, and tooth eruption. Root growth was unimpeded in 26 per cent,
      impaired in 55 per cent, and arrested in 19 per cent. Eruption of transplants
      occurred at the time of periodontal and alveolar healing, and before any
      significant root growth. Furthermore, autotransplanted premolars created growth
      of the alveolar process along with the eruption process.

PMID- 9558765
TI  - Early radiographic diagnosis of apical root resorption during orthodontic
      treatment: a study of maxillary incisors.
AB  - The purpose of this study was to evaluate the sensitivity of digital radiographs
      for detection of (i) simulated root resorption cavities in an experimental model
      and (ii) orthodontically-induced apical root resorption in vivo. The severity of
      root resorption after 3 and 6 months treatment was studied in relation to root
      form. The experimental study cavities, drilled in mandibular roots in a dry
      skull, were recorded in conventional and digital radiographs. In vivo root
      resorption was evaluated on digital radiographs of 92 maxillary incisors after 3
      and 6 months treatment with fixed appliances. The results showed a similar
      sensitivity for the two methods. Sensitivity increased significantly with cavity
      size. After 3 months apical root resorption was detected in only a few teeth. The
      number had increased significantly after 6 months. There was a higher degree of
      root resorption in teeth with blunt and pipette-shaped apices. In such teeth a 3
      month radiographic control is recommended.

PMID- 9558766
TI  - The relationship between irregularity of the incisor teeth, plaque, and
      gingivitis: a study in a group of schoolchildren aged 11-14 years.
AB  - The relationship between irregularity of teeth and periodontal disease was
      investigated in 201 children aged 11-14 years. The upper and lower incisor teeth
      were assessed for spacing, labio-lingual displacement, and mesiodistal overlap at
      each of the six contact areas. Plaque and gingivitis were assessed at six sites
      on each of the four upper and four lower incisor teeth. There was evidence for a
      direct relationship between the number of contact areas with tooth displacement
      combined with overlap and the number of sites with gingival redness (R = 0.25, P
      < 0.001), bleeding (R = 0.18, P < 0.01), and profuse bleeding (R = 0.25, P <
      0.001). There was no evidence for a relationship between labio-lingual
      displacement alone and gingivitis. One-hundred-and-twenty-eight subjects without
      tooth displacement combined with incisor overlap had, respectively, 34, 15, and
      35 per cent fewer sites with redness (P < 0.01), bleeding (P < 0.05), or profuse
      bleeding (P < 0.01) than the 73 subjects with overlap. The statistical
      significance of these differences was unaffected by covariate adjustment to take
      account of the effect on gingivitis of variation in the number of sites with
      plaque. There was no evidence of a relationship between incisor overlap and
      amount of plaque in these subjects. The results indicate that overlapping of
      incisor teeth is directly related to gingivitis and this relationship cannot be
      explained simply by an effect on oral hygiene.

PMID- 9558767
TI  - Dental maturation in subjects with extreme vertical facial types.
AB  - The purpose of this research was to investigate whether there is a difference in
      dental maturation between skeletal open bite and skeletal deep bite subjects of
      the same chronological age. The material consisted of 40 lateral headfilms and 40
      panoramic radiographs of 20 male and 20 female white subjects, with a mean
      chronological age of 9 years and 2 months (range: 7 years 6 months to 10 years 11
      months). These subjects were selected on the basis of lower anterior face height
      as a percentage of total face height and on the amount of open or deep-bite from
      a total sample of 400 subjects. The persons exhibiting the most extreme values at
      both ends of the distribution were selected to create two groups with 20 subjects
      in each (10 males and 10 females). Thus, the groups represented subjects with
      either a large lower anterior face height associated with an open bite or a small
      lower anterior face height associated with a deep bite. A double blind
      determination of dental maturation, expressed by dental age, for each subject was
      performed on the panoramic radiographs using the system of Demirjian et al.
      (1973). A covariance analysis was used to eliminate variability introduced by the
      large age range of the sample. The skeletal open bite and deep bite groups
      presented mean dental ages of 120.48 and 114.00 months, respectively. Statistical
      analysis demonstrated that this difference was statistically significant at P <
      0.05. Therefore, it seems that skeletal open bite subjects presented a slight
      tendency to have an advanced dental maturation, expressed by dental age, as
      compared with skeletal deep bite subjects.

PMID- 9558768
TI  - Surface roughness of orthodontic wires via atomic force microscopy, laser
      specular reflectance, and profilometry.
AB  - The surface roughness of orthodontic archwires is an essential factor that
      determines the effectiveness of arch-guided tooth movement. Using the non
      destructive techniques of atomic force microscopy (AFM) and of laser specular
      reflectance, the surface roughness of 11 nickel-titanium orthodontic wires, a
      stainless steel and a beta-titanium wire was measured. The results were compared
      with those obtained using surface profilometry. The smoothest wire, stainless
      steel, had an optical roughness of 0.10 micron, compared with 0.09 micron from
      AFM and 0.06 from profilometry. The surface roughness for the beta-titanium wire
      measured by all three methods was approximately 0.21 micron, while that of the
      NiTi wires ranged from 0.10 to 1.30 microns. As the surface roughness not only
      affects the effectiveness of sliding mechanics, but also the corrosion behaviour
      and the aesthetics of orthodontic components, the manufacturers of orthodontic
      wires should make an effort to improve the surface quality of their products.

PMID- 9558769
TI  - Morphological aspects of the mid-palatal suture in the human foetus: a light and
      scanning electron microscopy study.
AB  - Morphological features of the mid-palatal suture were studied in human foetuses
      from 4 to 9 months of intra-uterine life. The foetuses were divided into three
      age groups, GI (16-23 weeks), GII (24-31 weeks) and GIII (32-39 weeks). The mid
      palatal suture in GI foetuses is rectilineal in form with a wide space between
      the palatal processes of the maxilla. The suture has a sinuous nature in GII and
      GIII foetuses due to growth of the bone processes crossing the mid-line. A wide
      zone of cellular proliferation observed in GI narrows in GII and GIII foetuses.
      The imbricating nature of the suture in GII and GIII is caused by bone growth
      adjacent to the mid-palatal suture. Sharpey's fibres, emerging from the bone
      processes, run to the median region of the mid-palatal suture and are observed
      from GI foetuses onwards. The collagen fibres of the mid-palatal suture are
      orientated transversely under the oral epithelium and exhibit a regular meshwork
      with a predominance of sagittal fibres in the median region of the suture. These
      fibres are orientated transversely and obliquely at the junction with the nasal
      septum.

PMID- 9558770
TI  - Helicobacter-related diseases today.

PMID- 9558771
TI  - Seat-belt injuries to the supra-aortic trunks.
AB  - Five seat-belt related injuries to the supra-aortic and cervical vessels
      occurring in four patients are reported. All patients but one were symptomatic,
      none presented with stroke, and in one case arterial lesion was revealed by
      delayed onset of symptoms. Outcome of surgical treatment was overall good.
      Systematic search of such injuries and surgical repair of those without major
      neurological signs might be advisable.

PMID- 9558772
TI  - Immediate TRAM flap breast reconstruction in an obese patient with relapsing
      benign phyllodes tumor: report of a case.
AB  - The authors present a case of relapsing benign phyllodes cystosarcoma of the
      breast in an obese female treated with a simple mastectomy and an immediate
      reconstruction using a bipedicled transverse rectus abdominis musculocutaneous
      (TRAM) flap. After a brief review of treatment options for phyllodes tumors, they
      discuss the advantages of TRAM flap breast reconstruction, suggesting that it may
      also be applied in obese patients.

PMID- 9558773
TI  - A case of pediatric systemic lupus erythematosus with early onset and unusual
      serologic and clinical findings.
AB  - The authors report on a case of Pediatric Systemic Lupus Erythematosus (SLE) in a
      female child aged 3 1/2 with a set of peculiar clinical and serologic
      characteristics; early onset of the disease, non-specific clinical signs, high
      serum levels of IgG and a clinical course characterized by the absence of renal
      neurological and articular involvement.

PMID- 9558774
TI  - Rifaximin and Helicobacter pylori eradication.
AB  - In this study, we tested the effectiveness of Rifaximin, a surface antibiotic
      which is not absorbed when given orally, in the eradication of Helicobacter
      pylori (HP). The drug was combined in triple therapy either with Amoxicillin and
      Omeprazole or with Erythromycin-ethylsuccinate and Omeprazole. Twenty-three
      patients complaining of dyspeptic symptoms and gastric infection due to HP were
      evaluated. The patients were randomly given one of the following therapeutic
      protocols: Rifaximin susp. 600 mg/day x 3/day (at least two hours after meals:
      10:00 am, 2:00 pm, 9:00 pm), Amoxicillin tab. 1 g x 2/day (at least two hours
      after meals: 10:00 am, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before
      breakfast) (protocol A) and Rifaximin susp. 600 mg/day x 3/day and Erythromycin
      ethylsuccinate tab. 600 mg x 3/day (at least two hours after meals: 10:00 am,
      2:00 pm, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast)
      (protocol B). Both therapeutic protocols were prescribed for two weeks. At least
      one month after the end of the treatment the patients were controlled to
      ascertain eradication of the infection. The follow-up carried out after treatment
      showed that HP infection was eradicated in 6 of 10 patients in the first group
      (protocol A) and in 1 of 10 in the second group (protocol B). These patients were
      HP-negative in all the tests performed: histological, CP-TEST, culture test. The
      data collected showed a reasonable level of effectiveness of the protocol using
      the combination Rifaximin-Amoxicillin and Omeprazole. However, they do not differ
      from the reported data in the literature which show a similar effectiveness of
      the combination Omeprazole-Amoxicillin at the same doses. Different formulations
      that makes it possible for the drug to reach these "protected areas" would
      probably be more effective.

PMID- 9558775
TI  - Anti-TNF-alpha antibodies are not associated with Helicobacter pylori induced
      gastritis.
AB  - Over the past few years, it has been suggested that increased gastric production
      of some cytokines, including tumor factor-alpha (TNF-alpha), play a crucial role
      in the pathogenesis of H. pylori associated gastroduodenal diseases. On the other
      hand, it has been postulated that the presence of autoantibodies directed against
      several cytokines could represent or a down-regulatory response of the host to
      limit the damage associated with chronic bacterial infection or a specific
      cytokine inhibitor. The aim of this study was to evaluate whether serum anti-TNF
      alpha antibodies are produced in response to H. pylori infection. The anti-TNF
      alpha antibody titer among H. pylori positive and H. pylori negative patients
      showed no statistically significant difference. Interestingly, after eradication
      of H. pylori, no significant modification in anti-TNF-alpha antibody levels was
      found. In H. pylori positive patients, no correlations (either positive or
      negative) was demonstrated between anti-TNF-alpha antibody and activity of
      gastritis, nor between these antibodies levels and presence of duodenal ulcer.
      The lack of correlation between anti-TNF-alpha antibody levels and activity of
      gastritis indicates that these autoantibodies do not affect the clinical course
      of the H. pylori associated gastroduodenal diseases. Therefore, the biological
      and clinical relevance (if any) of anti-TNF-alpha antibodies in H. pylori
      associated gastritis remains to be better elucidated.

PMID- 9558776
TI  - Evaluation of cardiovascular parameters by continuous 24 hour monitoring in
      diabetic hypertensive patients with autonomic neuropathies.
AB  - Correlations between scores of autonomic neuropathy severity in diabetic
      hypertensive subjects and behaviour of cardiovascular parameters detected by
      continuous 24 hour monitoring were investigated in order to reveal any
      alterations hat indicated onset and progression of disautonomy. R-R and Q-T
      patterns, circadian pressure rhythm and ECG Holter over 24 hours were analysed in
      30 patients divided into various groups (age, duration of disease, treatment) and
      10 controls. Three autonomic tests (deep breathing, postural hypotension, lying
      to standing) were performed and the relative Ewing scores recorded. Data obtained
      were analysed using Pearson's correlation test and simple linear regression. The
      results not only confirm circadian rhythm demodulation of arterial pressure, but
      also show progressive correlation between the scores obtained and modified
      cardiovascular parameters. According to the authors, detection of these
      intermediate alterations may be useful in forecasting possible onset or evolution
      of dysautonomic pathologies.

PMID- 9558777
TI  - A diary model for monitoring blood pressure in the elderly.
AB  - Activity can significantly change blood pressure. Twenty four hour ambulatory
      blood pressure monitoring (Holter method) was introduced to optimize diagnosis
      and the changes in blood pressure. It was flanked by the purpose to use diaries
      to correlate symptoms and pressure changes, pressure changes and psychophysical
      activity, life style and drugs. The diary model adopted by us for 380 elderly
      subjects between 65 and 85 years old is divided into four main sections: 1.
      general activities (8 items); 2. situational variations (7 items); 3. correlation
      between symptoms and pressure changes; 4. drug treatment and pressure changes.
      The aim of our study was to assess the compliance of the elderly to keeping a
      diary. Our results showed that compliance was satisfactory in 352/380 subjects
      (93%).

PMID- 9558778
TI  - Calcified retroperitoneal fibroma.
AB  - A case of 31-year-old male with a retroperitoneal tumor is described. Abdominal
      ultrasound revealed a left para-aortic calcific mass, adjacent to the left lobe
      of the liver and to the upper pole of the left kidney. A CT-scan of the abdomen
      showed the mass to originate from the left adrenal gland. At operation, a large,
      retroperitoneal mass, adherent to the left kidney and the spleen, but not
      infiltrating, was excised. Histologically the tumor was diagnosed as a calcified
      osteo-producing fibroma. Benign retroperitoneal tumors represent about 25% of all
      retroperitoneal neoplasm. This reported case represents a retroperitoneal tumor
      of slow growth and benign clinical course whose characteristic consists of the
      heavy calcifications which are normally absent in a fibroma type mass.

PMID- 9558779
TI  - Pursuing health care fraud and abuse.

PMID- 9558780
TI  - Deconstructing the Columbia/HCA investigation.
AB  - Every issue raised by the current investigation into the business practices of
      Columbia/HCA serves as a signpost for the progress and problems inherent in
      market-driven health care reform. Actions against Columbia/HCA by regulators
      reveal deeply rooted resistance to the profit-motivated reforms embodied in the
      company's philosophy: the public's reluctance to accept necessary reductions in
      excess hospital capacity; the legal and cultural obstacles to the overdue
      alignment of physician and hospital economic interests; and the myriad
      reimbursement and accounting problems involved in the vertical integration of
      health care delivery. The investigation also underscores the antiquation of the
      reimbursement mechanisms and control systems in place for financing the delivery
      of care to Medicare beneficiaries.

PMID- 9558781
TI  - Columbia/HCA: a failure of leadership.

PMID- 9558782
TI  - Columbia/HCA: villain or victim?

PMID- 9558783
TI  - Market realities meet balanced government: another look at Columbia/HCA.

PMID- 9558784
TI  - Costs and use of mental health services before and after managed care.
AB  - This paper tracks access, utilization, and costs of mental health care for a
      private employer over nine years during which mental health benefits were carved
      out of the medical plan and managed care was introduced. Prior to the carve-out,
      mental health costs increased by around 30 percent annually; in the first year
      after the change, costs dropped by more than 40 percent; in the six follow-up
      years, costs continued to decline slowly. This cost reduction was not
      attributable to decreased initial access, as the number of persons using any
      mental health care increased following the change. Instead, the cost reduction
      was the result of (1) fewer outpatient sessions per user, (2) reduced probability
      of an inpatient admission, (3) reduced length-of-stay for an inpatient episode,
      and (4) substantially lower costs per unit of service.

PMID- 9558785
TI  - Costs and incentives in a behavioral health carve-out.
AB  - A carve-out of mental health and substance abuse services initiated in 1993 by
      the Group Insurance Commission (GIC) of the Commonwealth of Massachusetts
      resulted in changes in the costs of those services. Those changes were related to
      incentives in the contract between the GIC and its managed behavioral health
      vendor. Total and plan costs were reduced by 30-40 percent after adjusting for
      trends. Incentives to produce savings of this magnitude not only were a
      consequence of the payer/vendor contract but, we speculate, derive from the
      growth potential facing companies in the managed behavioral health care market.

PMID- 9558786
TI  - Beyond health promotion: reducing need and demand for medical care.
AB  - A population's medical need represents its illness burden. Medical demand
      represents the service level requested for a particular need. Medical care costs
      are, in large part, a function of need and demand. Our review of health education
      programs designed to reduce health risks and reduce costs identified thirty-two
      programs with documented effectiveness, generally achieving claims reductions of
      20 percent. Specific program features including chronic disease self-management,
      risk reduction, and increased self-efficacy appear important. A broadened
      definition of health promotion focused on increased personal responsibility for
      health-related actions and directed at improvement of long-term health outcomes
      also could reduce health care costs.

PMID- 9558787
TI  - Analyzing the evidence on European health care reforms.
AB  - Health system reform, in Europe as elsewhere, has often been influenced as much
      by theory and conjecture as by fact and experience. In a study published in
      September 1997, the Regional Office for Europe of the World Health Organization
      (WHO) drew together the available evidence about the health care systems in the
      fifty-one countries of the European region. This paper focuses on western
      European countries. It reviews a variety of policy strategies and then explores
      implications from this European experience for the formulation of U.S. health
      care policy.

PMID- 9558788
TI  - Courts as gatekeepers in managed care settings.

PMID- 9558789
TI  - The 'Mona Lisa' of health policy: primary care at home and abroad.

PMID- 9558790
TI  - Children's health insurance, access to care, and health status: new findings.
AB  - Despite various policy initiatives, a substantial number of children in the
      United States remain uninsured, have problems with access to health care, or are
      in fair or poor health. These difficulties are not evenly distributed across the
      population. Hispanic children, those whose parents have little education, and
      those who live in families without an employed parent are at disproportionately
      high risk of encountering these problems. Although multivariate analyses would be
      required to disentangle the complex relationships among these factors, these
      descriptive data reveal the segments of the population to which new health
      related programs, such as CHIP-funded state plans, might most productively be
      directed. Issues concerning children's health are likely to remain on the
      national policy agenda for some time to come. Because MEPS is a continuing data
      collection effort, it will enable researchers and policymakers to follow trends
      in these issues over time. For example, MEPS data will support evaluations at the
      national level to determine whether children who lack health insurance or a usual
      source of care will actually face fewer barriers after CHIP-funded programs are
      implemented. This paper provides a baseline against which to evaluate the impact
      of CHIP and other policy changes on the health and well-being of America's
      children.

PMID- 9558791
TI  - Insurance agents: ignored players in health insurance reform.
AB  - In this paper we use the reforms to the individual health insurance market in New
      Jersey to illustrate the intricate interaction between insurance agents and
      insurance reform initiatives. Until recently, policymakers who designed reforms
      to the health insurance market largely ignored the role of agents in selling
      individual health insurance policies. These reforms have the potential to
      overturn the agent's traditional role, and agents can influence how the reforms
      are implemented.

PMID- 9558792
TI  - Addressing the needs of chronically ill persons under Medicare.

PMID- 9558793
TI  - Health plan accountability and reporting: issues and challenges.

PMID- 9558794
TI  - Potential effects of raising Medicare's eligibility age.
AB  - Recent fiscal pressures on Medicare and an already enacted increase in Social
      Security's normal retirement age have generated discussion of raising Medicare's
      age of entitlement. This DataWatch examines potential impacts of raising
      Medicare's eligibility age to sixty-seven on public-sector health spending and
      individual insurance coverage. The proposed increase would affect a substantial
      fraction of beneficiaries without having a commensurate effect on expenditures,
      even in the long run. It is estimated that if the eligibility age were sixty
      seven, upwards of 500,000 persons ages sixty-five and sixty-six would be left
      without any insurance, and even more would not be able to afford coverage with
      benefits similar to those of Medicare.

PMID- 9558795
TI  - Satisfaction with care: do Medicare HMOs make a difference?
AB  - Differences in satisfaction with care and perceptions of doctor/patient
      interactions were compared for Medicare beneficiaries enrolled in health
      maintenance organizations (HMOs) and beneficiaries in the fee-for-service (FFS)
      sector (nonenrollees). After controlling for covariates, beneficiaries expressed
      satisfaction with their care, regardless of where they received it. However, HMO
      enrollees were more likely than nonenrollees were to be very satisfied with the
      costs of care and with getting care at one location. In contrast, for every
      components-of-care measure, nonenrollees were more likely than HMO enrollees were
      to indicate high satisfaction with the quality of interaction with their
      physicians.

PMID- 9558796
TI  - Preventable hospitalizations and socioeconomic status.
AB  - "Preventable" hospitalizations have been proposed as indicators of poor health
      plan performance. In this study of elderly Medicare beneficiaries, however, we
      found that preventable hospitalizations are also more common among elders of
      lower socioeconomic status (SES). The relationship persisted even when an up-to
      date severity-of-illness adjustment system was used. To the extent that
      indicators of health plan "performance" reflect enrollees' characteristics, plans
      will be rewarded for marketing their services to wealthier, healthier, and better
      educated patients. Further work is needed to clarify issues of accountability for
      preventable hospitalizations and other putative indices of health plan
      performance.

PMID- 9558797
TI  - State regulation, payment policies, and nurse-midwife services.
AB  - State regulatory and reimbursement policies continue to exert a strong influence
      on health workforce policy. Surveys conducted in 1991 and 1995 for the purpose of
      examining the impact of state regulation on the supply and practice of certified
      nurse-midwives (CNMs) showed that the single best predictor of the distribution
      and practice activities of CNMs was the degree to which state policies
      facilitated or restricted CNM practice.

PMID- 9558798
TI  - Foundations today: finding a new role in the changing health care system.

PMID- 9558799
TI  - A U.S. Senator on government regulation.

PMID- 9558800
TI  - Medicare: still looking for solutions.

PMID- 9558801
TI  - Evils of cost shifting.

PMID- 9558802
TI  - A new commission to guide the managed care revolution.

PMID- 9558803
TI  - A combination approach to children's health insurance.

PMID- 9558804
TI  - Scope of hypnosis education in academia: results of a national survey.
AB  - The present article examines the current status of hypnosis training and the
      attitudes of program chairs toward inclusion of such training in doctoral
      education. A brief survey on hypnosis training was sent to all psychology
      doctoral programs accredited by the American Psychological Association (n = 218)
      as well as 24 nonaccredited doctoral programs. Twenty-six percent of responding
      programs (n = 44/170) report offering either required or elective coursework in
      hypnosis. Of those programs offering a course in hypnosis, the mean semester
      credit hours earned was 3. Although many program directors support opportunities
      for hypnosis education in doctoral education, other constraints (e.g., available
      faculty, required coursework) limit its availability.

PMID- 9558805
TI  - When hypnosis causes trouble.
AB  - Like any other effective intervention, hypnotic treatment can occasionally cause
      harmful effects as well as beneficial ones. The first step in avoiding clinical
      complications is recognizing that they can occur. A review of the literature,
      however, suggests a long-standing inattention to the potential harmfulness of
      hypnotic interventions, including patients' unexpected reactions, leading to
      clinical complications, including amnesia, catharsis, paralysis, disorientation,
      literalness of response, accelerated transference, and memory contamination. In
      addition to these unexpected reactions by patients, complications can also arise
      from a practitioner's need for power and by the inappropriately narrow focus on
      the hypnotic process itself, leading to distraction from the more fundamental
      clinical process.

PMID- 9558806
TI  - The inpatient treatment of patients suffering from (motor) conversion symptoms: a
      description of eight cases.
AB  - This article presents a preliminary study that used two controlled randomized
      trials to study the effect of hypnosis in the treatment of eight patients with
      (motor) conversion symptoms. Controlled research into the treatment of conversion
      symptoms is scarce and can often be criticized on methodological grounds. It
      would appear, however, that both the use of suggestive and behavioral therapeutic
      techniques and eclectic treatment programs yield good results in the treatment of
      conversion symptoms. The results of the study suggest that comprehensive clinical
      treatment including hypnosis has enough promise to be studied in clinical trials.
      In the interpretation of the results, special attention is given to primary
      diagnosis, duration of complaints, traumatic experiences in childhood,
      dissociative capacity, and hypnotizability.

PMID- 9558807
TI  - Surreptitious observation of responses to hypnotically suggested hallucinations:
      a test of the compliance hypothesis.
AB  - Suggestions for arm levitation and for visual, auditory, tactile, and taste
      hallucinations were administered twice via audiotape to a group of high
      suggestible students and low suggestible simulators. During one of the
      administrations, participants were led to believe they were alone, but their
      behavior was surreptitiously recorded on videotape and observed on a video
      monitor. During the other administration, they were observed openly by an
      experimenter who had not been informed about group assignment. When unaware that
      they were being observed, simulators were significantly less responsive to
      suggestion and engaged in substantially more role-inappropriate behavior. In
      contrast, the responsiveness of nonsimulating students was not affected by the
      presence of an experimenter, and they exhibited little role-inappropriate
      behavior even when alone. These data indicate that the responses of suggestible
      individuals reflect internally generated changes in experience and are not due to
      simple intentional compliance (i.e., faking).

PMID- 9558808
TI  - Posthypnotic responding: knowing when to stop helps to keep it going.
AB  - The authors examined the effect of specifying (cue) or not specifying (no cue)
      the cancellation cue for posthypnotic suggestion. Responding was indexed on
      formal, embedded, informal, and postexperimental tests. Thirty-six real,
      hypnotized participants and 20 simulating participants took part in an
      application of the real-simulating paradigm. Responding declined across the four
      tests. Real participants in the cue condition maintained responding longer than
      simulators in the cue condition, and they also maintained responding longer than
      reals and simulators in the no cue condition. The findings highlight the
      interactional influence of individual, interpersonal, and situational factors in
      posthypnotic responding and underscore the active involvement of individuals in
      hypnotically initiated events.

PMID- 9558809
TI  - If we build it, they will come.

PMID- 9558810
TI  - Personal problems? The Members' Assistance Program can help.

PMID- 9558811
TI  - Giving time to your profession can make a difference.

PMID- 9558812
TI  - Dementia's impact on pain sensation: a serious clinical dilemma for dental
      geriatric care givers.
AB  - Dementia's impact on pain sensation is not well understood. Very little research
      has been done in this area, our clinical knowledge is poor, and there is no
      published information available to practitioners. This article reviews the
      current literature and discusses the need for further research. The number of
      patients with dementia is growing. This patient group will require dental
      diagnosis and treatment, and cannot be ignored by dentists. A humane approach to
      treatment must be adopted.

PMID- 9558814
TI  - Dental practice review in Ontario.

PMID- 9558815
TI  - Patient satisfaction with dentures made by dentists and denturologists.
AB  - BACKGROUND: Within Quebec and elsewhere in Canada, patients requiring removable
      prostheses consult either dentists or denturologists. In this article, we
      describe the socioeconomic characteristics of 410 edentulous individuals seeking
      replacement of their dentures, and compare the levels of satisfaction experienced
      by the patient groups provided with conventional dentures by dentists and by
      denturologists. METHODS: All subjects responded to announcements seeking
      participants in a clinical trial. The announcements indicated that all
      participants would receive new prostheses. Data were collected via telephone
      interviews. Sociodemographic variables included sex, age, education level and
      family income. Subjects were asked to evaluate their present maxillary and
      mandibular prostheses for general satisfaction, stability, comfort, ability to
      chew, ability to clean and appearance. Age, cost and the provider (dentist or
      denturologist) of the original prostheses were also recorded, and responses were
      then compared between the groups of subjects treated by dentists (N = 91) and
      denturologists (N = 319). RESULTS: There were no significant differences in the
      sociodemographic characteristics of the two groups, except for a small difference
      in mean age (two years). Both groups had paid approximately the same amount for
      their complete prostheses. As expected, most individuals were satisfied with
      their maxillary prostheses, but dissatisfied with their mandibular prostheses.
      Significantly more subjects in the denturologist treatment group than the dentist
      treatment group gave their mandibular prostheses a poor rating for general
      satisfaction (p = 0.003), comfort (p = 0.04) and stability (p = 0.016).
      CONCLUSIONS: These results suggest that the edentulous patients treated by
      dentists and denturologists share similar sociodemographic characteristics, and
      pay a similar cost for treatment. However, those treated by denturologists seem
      to be more dissatisfied with their mandibular prostheses than those treated by
      dentists.

PMID- 9558813
TI  - The forgotten discipline of dentistry.

PMID- 9558816
TI  - Determinants of positive and negative attitudes toward dentistry.
AB  - Previous studies have primarily investigated the determinants of negative
      attitudes toward dentistry. Little is known about the reasons for positive
      attitudes. Using a group of university students who were surveyed during 1996,
      this study therefore examined both positive and negative attitudes to dentistry.
      It was initially predicted that dentally anxious individuals would be more likely
      to have negative feelings about dentistry than non-dentally anxious individuals,
      and would attribute this attitude to specific experiences. The study found that
      the majority of participating students had a positive attitude toward dentistry,
      and that participants with low levels of dental anxiety were more likely to have
      a positive attitude than those with a high level of anxiety. However, highly
      dentally anxious individuals were just as likely to feel positive toward
      dentistry as they were to feel negative. A substantial proportion of students
      claimed to have had painful or distressing experiences at the dentist during
      their adolescence. However, experiencing a painful or distressing incident was
      not related to having a negative attitude. The majority of the students who felt
      negative toward dentistry attributed this attitude to an unspecific experience,
      although dentally anxious individuals were likely to be more specific than non
      dentally anxious individuals. Women participants appeared to have experienced
      painful or distressing incidents at a younger age than the men. The authors
      concluded that the factors involved in the development and maintenance of an
      individual's attitude toward dentistry are complex, and that dentists should be
      concerned with the promotion of positive attitudes rather than attempting to
      resolve negative ones.

PMID- 9558817
TI  - Posterior composite resin simplification--what of scientific validation?

PMID- 9558818
TI  - Eating disorders among college women: prevention, education, and treatment
      responses.
AB  - Eating-related problems, particularly among college women, represent a
      significant health concern on university campuses. Body image dissatisfaction,
      weight preoccupation, and unhealthy weight management are prevalent among even
      normal-weight students, but discussions of broad college health interventions in
      this area have been limited. Two conceptual tools that are useful in developing a
      comprehensive health center response to eating disorders in the college setting
      are described. The diagnosis of Eating Disorders Not Otherwise Specified is
      suggested as a framework for defining target populations and eating problems
      requiring intervention, and a picture of the prototypical eating problem
      candidate is developed. A multiple-level model of intervention that includes
      preventive, intermediate, and remedial responses to varied forms of eating
      related concerns is described. The intervention model is illustrated with
      examples, and limitations of the method are discussed.

PMID- 9558819
TI  - Vitamin C status of a campus population: college students get a C minus.
AB  - Diet and the vitamin C status of two samples of college students were examined.
      Nonsmoking participants were recruited from a campus population during the fall
      and winter months. The prevalence of vitamin C deficiency (plasma vitamin C
      concentrations less than 11 mumol/L) ranged from 1% to 2% in the sampled campus
      populations. Marginal vitamin C status (plasma vitamin C concentrations from 11
      to less than 28 mumol/L) was observed in 12% of the fall sample and 16% in the
      winter sample. Participants with marginal vitamin C status consumed significantly
      fewer servings of fruits and vegetables daily than participants with adequate
      vitamin C status. Marginal vitamin C status, which is even more pronounced in
      smokers, has been associated with fatigue and increased severity of respiratory
      tract infections. Because the vitamin C status of many college students, both
      smokers and nonsmokers, may be inadequate, health promotion or wellness programs
      for all students should emphasize the importance of adequate fruit and vegetable
      consumption.

PMID- 9558821
TI  - Pregnancy testing and counseling: a university health center's 5-year experience.
AB  - Profiles and related sexual histories of 2,029 women who sought pregnancy tests
      at a university health center over a 5-year period were examined. Rates of
      pregnancy (30%) were consistent over the 5 years. The highest rates of testing
      were among seniors and juniors, with graduate students reporting the highest
      levels of unintended pregnancy. More than 37% of the women indicated they had not
      used any method of contraception at the time of risk; 29% of the women who had
      used condoms reported that the device had either torn or slipped off. The women
      with previous pregnancies were more likely to test positive and to terminate the
      pregnancy than were the women who had never been pregnant. The findings are
      discussed with reference to sexually education programs and pregnancy counseling.

PMID- 9558820
TI  - Obstacles to condom use: the combination of other forms of birth control and
      short-term monogamy.
AB  - Two hundred thirty-seven college students involved in heterosexual relationships
      were surveyed to determine the effects of relationship type and use of forms of
      contraception other than condoms on condom use. Findings indicated that in the
      context of a short-term, monogamous relationship, the use of another form of
      birth control was associated with decreased condom use. In addition, 20% of the
      participants reported that they had wanted to use a condom for disease prevention
      on at least one occasion but had decided not to do so because they were using
      another form of contraception. Implications for preventive health are discussed.

PMID- 9558823
TI  - The medical excuse game as it is played at Duke University.

PMID- 9558822
TI  - Alcohol consumption, strength of religious beliefs, and risky sexual behavior in
      college students.
AB  - Relationships among alcohol use, strength of religious convictions, and unsafe
      sexual practices of 210 students at a large public university in the "bible belt"
      were examined. The women with strong religious beliefs consumed less alcohol and
      were less likely to engage in risky sexual behavior than were female participants
      with weaker religious convictions. Among the men, religious conviction was not
      significantly correlated with alcohol consumption or risky sexual behavior, but
      alcohol consumption and inconsistent use of condoms and multiple sexual partners
      were significantly correlated. Men had higher rates of alcohol consumption and
      unprotected sexual activity than women did, yet the two groups did not differ in
      overall frequency of sexual activity. Future research is needed to (a) provide
      greater understanding of gender differences in alcohol use, risky sexual
      behavior, and religious beliefs of college students in the region and (b)
      determine whether similar correlations exist in other areas of the country.

PMID- 9558824
TI  - Multitracer studies on the accumulation of radionuclides in mushrooms.
AB  - We used the multitracer technique to study the transfer of several radionuclides
      to two mushroom species. Radionuclides accumulated in the fruiting bodies of the
      mushrooms in the order of 83Rb > 65Zn > 54Mn > 22Na > 75Se and 85Sr > 60Co > 88Y,
      102Rh, 139Ce, 143.144Pm, 146.153Gd and 173Lu > 175Hf. The concentration ratio
      values for 83Rb, 65Zn and 54Mn in the fruiting bodies were more than 10, whereas
      those for 60Co, 88Y, 102Rh, 121mTe, 175Hf and the rare earth elements were less
      than 1. There were major differences in the accumulations of the alkali elements.

PMID- 9558825
TI  - Chromosome aberrations in bone marrow cells of C3H/He mice at an early stage
      after whole-body irradiation.
AB  - Murine acute myeloid leukemia is characterized by chromosome 2 aberrations, and
      genesis of the marker chromosome 2 by radiation is suspected to be an initiating
      event of radiation leukemogenesis. A detailed analysis of the type and frequency
      of chromosome 2 aberrations in murine bone marrow cells at an early stage after
      irradiation is provided here. A total of 40 male C3H/He mice was exposed to 137Cs
      gamma-ray at a dose of 1, 2 or 3 Gy, and sacrificed 24 hours after irradiation.
      Metaphase samples prepared from bone marrow cells were Q-banded for karyotyping
      or painted with DNA probes specific to chromosome 2. In 5 mice analyzed by
      karyotyping, one mouse showed high frequency of the marker aberrations as well as
      other chromosome 2 aberrations. Chromosome painting analysis for the rest of the
      mice also detected 3 animals showing significantly high frequencies of chromosome
      2 aberrations. Dose-dependence of the frequencies was observed even among those
      mice that tended to be sensitive. The results indicated that there was a subgroup
      of mice carrying hypersensitive chromosome 2. The subgroup could be leukemia
      sensitive if radiation-induced chromosome aberrations are responsible for an
      early change in myeloid leukemogenesis.

PMID- 9558826
TI  - Single dose radiocurability of four murine solid tumors and a predictive assay
      for the curability in situ.
AB  - Correlations between radiocurability and kinetic parameters were investigated in
      four transplantable tumor types in WHT/Ht mice. The radiation dose to achieve 50%
      tumor control at 120 days after irradiation, i.e., TCD50/120, was 30 Gy for
      squamous cell carcinoma H, 32 Gy for squamous cell carcinoma NOS, 46 Gy for
      rhabdomyosarcoma KAS, and 63 Gy for fibrosarcoma YAS. The tumor cell kinetic
      parameters investigated were specific growth delay, volume doubling time, 125I
      iododeoxyuridine (IUdR) uptake rate, and specific cell loss rate. The specific
      cell loss rate was defined as the ratio of cell loss rate in non-irradiated
      tumors to the rate in irradiated tumors, and was obtained by measuring the
      retention rate of radioactivity in the tumors. No correlations were found between
      specific growth delay, volume doubling time, 125I-IUdR uptake rate, and TCD50.
      However, the specific cell loss rate correlated with the TCD50. Therefore, the
      125I-IUdR labeling method may be useful as an in situ predictive assay for tumor
      radiocurability.

PMID- 9558827
TI  - Single-strand breaks in oligodeoxyribonucleotides induced by fission neutrons and
      gamma radiation and measured by gel electrophoresis: protective effects of
      aminothiols.
AB  - The technique of high-resolution gel electrophoresis using
      oligodeoxyribonucleotides of known composition as model systems, offers a simple
      quantitative estimate of DNA damage in aqueous solution induced by ionizing
      radiation. The fraction of damaged DNA can be quantitatively defined in terms of
      the increased electrophoretic mobilities of the damaged oligonucleotides,
      relative to the mobility of the unirradiated and intact oligonucleotides. The
      usual direct strand breaks can be observed at gamma-ray dosages of 200 Gy.
      However, at a gamma-ray dosage of 400 Gy, only a broad background, attributed to
      heterogeneously and multiply damaged oligonucleotide fragments with overlapping
      and varying electrophoretic mobilities, can be distinguished. On the other hand,
      individual bands due to resolvable DNA fragments are evident even at dosages as
      high as 400 Gy for fission neutrons. When double-stranded oligonucleotides are
      exposed to gamma-ray dosages of 200 Gy, the fraction of damaged DNA approaches 30
      40%. This damage can be almost completely suppressed (> 99%) if the irradiations
      are conducted in aqueous solutions in the presence of 0.5-1.0 mM concentrations
      of the thiols cysteamine or 3-(3-methylaminopropylamino)propanethiol (WR-151326).
      The rate constant of reaction of OH radicals with small double stranded
      oligonucleotides 16 base pairs long, KDNA, is found to be closer to the diffusion
      controlled value (> 3 x 10(9) M-1 s-1) than the magnitudes of KDNA for the higher
      molecular weight, native DNA reported in the literature. These observations
      suggest that oligonucleotides represent more simple model systems than native DNA
      in solutions for studying the mechanisms of radioprotection exerted by thiols of
      different structures.

PMID- 9558828
TI  - Conversion of cycles per minute to hertz incorrect.

PMID- 9558829
TI  - Infection with the human immunodeficiency virus (HIV) may have occurred as early
      as the late 1940s.

PMID- 9558830
TI  - Partners for two decades: AOA and the National High Blood Pressure Education
      Program.

PMID- 9558831
TI  - Effect of lymphatic and splenic pump techniques on the antibody response to
      hepatitis B vaccine: a pilot study.
AB  - Osteopathic manipulative treatment (OMT) facilitates the movement of lymphatic
      fluid and may enhance the immunologic response to infection or injected antigen.
      In this investigation, two groups of volunteers were vaccinated with recombinant
      hepatitis B vaccine, given at 0, 5, and 25 weeks. The experimental group (n = 20)
      received OMT (lymphatic and splenic pump) three times per week for 2 weeks after
      each vaccination. Control subjects (n = 19) received vaccine but no OMT.
      Resultant serum antibody levels were measured by enzyme immunoassay. Fifty
      percent of subjects in the treatment group achieved protective antibody titers (>
      or = 10 mIU/mL) on the 13th week with an average titer of 374 mIU/mL. Only 16% of
      the control subjects had positive antibody responses, with average titers of 96
      mIU/mL. At all time points from week 6 on, the average anti-hepatitis B titer was
      higher in the treatment group than in the control group. These data suggest an
      enhanced immunologic response in subjects who received OMT.

PMID- 9558832
TI  - Utilization of nicotine nasal spray in smoking cessation.
AB  - It is widely accepted that nicotine replacement therapy can help patients to quit
      smoking. Recent approval by the US Food and Drug Administration of a nicotine
      nasal spray gives clinicians greater flexibility in choosing the best replacement
      therapy for a particular patient. Four types of smoking cessation therapy are
      currently available (gum, patch, nasal spray, and bupropion). These differ with
      respect to their onset and duration of action, adverse effects, and cost. This
      article focuses on which patients may benefit most from the use of nicotine nasal
      spray. Instructions for proper administration and dosing of the nicotine nasal
      spray are discussed as well as how to taper it appropriately, and how to avoid-
      and manage--adverse effects. Additionally, the cost of the nicotine nasal spray
      is reviewed and compared with over-the-counter products and bupropion. Resources
      for behavioral support are provided as well.

PMID- 9558833
TI  - Communication for osteopathic manipulative treatment (OMT): the language of lived
      experience in OMT pedagogy.
AB  - Questions about the scientific merits of osteopathic manipulative treatment (OMT)
      and the search for consistent, effective teaching methods for OMT persist in the
      discourse of the osteopathic medical curriculum. Although grounded on scientific
      principles, the philosophy of osteopathic medicine in the words of Andrew Taylor
      Still, William G. Sutherland, and other prominent osteopathic medical scholars
      advances concepts in metaphoric language that may seem obscure and dated to many
      of today's students. Evidence in the literature of osteopathic medicine supports
      the congruence of phenomenology with the philosophy and methods used to teach
      OMT. Phenomenology offers an alternative paradigm to address questions of
      scientific merit and could provide a consistent language to a rigorous,
      scientific approach to communication for OMT pedagogy. The authors propose a
      solution for the tactical adaptation of a communication strategy based on an
      interpretation of osteopathic medical methodology and phenomenology.

PMID- 9558834
TI  - Neuroleptic malignant syndrome related to use of clozapine.
AB  - A 19-year-old man presented to a community hospital with a sudden change in level
      of consciousness, fever, and muscle rigidity. The patient had a history of
      schizophrenia and was being treated with clozapine. Despite a high index of
      suspicion for neuroleptic malignant syndrome, definitive care was delayed for
      more than 24 hours after the patient was transferred to a tertiary care center.
      This case illustrates the importance of primary care physicians being able to
      recognize and diagnose this syndrome, particularly as the use of atypical
      antipsychotic agents increases.

PMID- 9558835
TI  - Nebulized lidocaine in the treatment of refractory tussive syncope.
AB  - Tussive syncope is a rare condition that often responds to treatment of the
      underlying cause of coughing. Therefore, the workup and diagnosis of the cause is
      essential. However, at times, the cough is refractory to conventional treatment.
      The use of nebulized lidocaine in such instances may be an important adjunctive
      therapy.

PMID- 9558836
TI  - [Retinal light damage].

PMID- 9558837
TI  - [Method and evaluation of experimental retinal reattachment].
AB  - An animal model of retinal reattachment is needed to study experimental macular
      relocation and recovery of reattached retina. The purpose of this study was to
      develop and evaluate a simple technique of retinal reattachment. We used the
      right eye of 13 pigmented rabbits for this experiment. 3 weeks before the
      operation, the eyes underwent a gas induced vitreous compression with sulfur
      hexafluoride gas. Transcleral subretinal hydrodissecction was used to create a
      partial (60-70% of the whole retina) retinal detachment. Retinal reattachment was
      observed in ten eyes 18 hours after the operation. The dark-adapted
      electroretinograms (ERGs) were recorded in 3 rabbits from 3 days to 3 months
      after the surgery. Selected eyes were enucleated for histology. The amplitude of
      ERGs (a-wave and b-wave) were reduced to 30% and 40% of the control eyes on day
      3. These waves were restored up to 70% and 80% of normal at 2 weeks and showed no
      significant changes thereafter. Degeneration and loss of photoreceptors in the
      early days after surgery as seen by light microscopy were almost completely
      restored to normal at 3 months after surgery. This model provides large retinal
      detachment and reattachment with minimized inflammatory response.

PMID- 9558838
TI  - [Effect of ultraviolet-filtering contact lens on rabbit eyes after exposure to
      ultraviolet light].
AB  - We evaluated the protective effect of a newly designed soft contact lens (SCL) on
      rabbit eyes. This SCL absorbs the ultraviolet B light of wavelengths between 280
      nm and 320 nm. Three weeks after resecting the nictitating membrane, the rabbit
      corneas were covered either by the new SCL or a conventional SCL. The eyes were
      exposed to ultraviolet light from two 15 W lamps placed 20 cm anteriorly for 3
      hours. Another three hours after the exposure, the cornea was examined first with
      a slitlamp biomicroscope after staining with fluorescein and then by
      histopathological means after enucleation. Six eyes wearing the new SCL showed
      moderate superficial punctate keratopathy. Six eyes wearing conventional SCL
      showed severe superficial keratopathy or corneal erosion. These findings were in
      good agreement with the histopathological findings. The new ultraviolet-filtering
      SCL was thus effective in protecting the rabbit cornea under our experimental
      conditions.

PMID- 9558839
TI  - [Clinical features of 10 cases with phlyctenular keratitis].
AB  - We investigated 15 eyes of 10 patients with phlyctenular keratitis. The patients
      were 6 men and 4 women, and their ages ranged between 3 and 56 years (mean, 17.8
      years). The follow-up periods ranged from 0.5 to 48 months (mean, 14 months).
      Clinically, complications in many cases were papillary hyperplasia in palpebral
      conjunctiva, meibomian gland infarct, chalazion, and blepharitis. Microbial
      examination from the lid margin before treatment revealed bacteria in 4 eyes of 4
      patients out of 9 eyes of 8 patients. The level of serum specific IgE antibody
      was high in only 1 patient out of 6. We classified the clinical course into 3
      stages, namely, infiltrative, nodule, and cicatricial stages. We also
      investigated the transition of the disease among the stages. All the cases of the
      infiltrative stage progressed to the nodule stage, and 92% of the nodule stage
      went on to the cicatricial stage. However 14% of the cicatricial stage cases
      reverted to the infiltrative stage and 7% to the nodule stage.

PMID- 9558840
TI  - [Correlation of pathological features of surgically excised choroidal neovascular
      membranes with age-related macular degeneration and indocyanine green
      videoangiographic findings].
AB  - We surgically excised subfoveal neovascular membranes from eight patients with
      age-related macular degeneration. The correlation of the histopathological
      features of choroidal neovascularization and preoperative indocyanine green (ICG)
      videoangiographic findings were studied. Neovascular membranes which demonstrated
      hyperfluorescence at an early phase of ICG videoangiography had many vascular
      channels and a large lumen without enclosure of retinal pigment epithelium (RPE).
      Fibrovascular tissues contained small vessels with fibrotic stroma that showed
      hyperfluorescence only at a late phase of ICG videoangiography. In contrast, the
      membrane which showed hypofluorescence of ICG videoangiography was composed of
      paucivascular fibrotic tissue covered extensively with RPE. Moreover, newly
      formed vessels with proliferative endothelium could be observed in the
      neovascular membranes that showed weak fluorescence or hypofluorescence. These
      results could provide a morphological basis for the interpretation of ICG
      videoangiographic features of choroidal neovascularization. It also may be useful
      in planning the treatment for subfoveal neovascular membranes.

PMID- 9558842
TI  - [Mobility of orbital implant covered by own sclera].
AB  - We evaluated in 7 eyes the mobility of a newly designed orbital implant made of
      hydroxyapatite. This orbital implant has a screw peg and is covered with a piece
      of sclera from the enucleated eye of the patient. The implant was well tolerated
      and there were no cases of proptosis during the follow-up of 1.8 +/- 0.6 years.
      Assuming the mobility of a healthy eye as 100%, photographic analysis showed the
      mobility of the anterior orbit to be 92.6% in adduction, 85.9% in abduction,
      84.9% in supraduction, and 90.9% in infraduction. The mean tugging weight of the
      implant was, when measured by a strain gauge, 344.2 +/- 29.2 g in adduction and
      327.6 +/- 33.4 g in abduction. These values corresponded to 90.4 +/- 4.4% and
      89.5 +/- 5.3% respectively of those in a healthy eye. The presence of the orbital
      implant did not affect the electrooculogram as compared to a healthy eye.
      Cinematic studies using magnetic resonance imaging (MRI) showed that the
      constriction and extension of the extraocular muscles, which were sewn onto the
      orbital implant, matched that of a healthy eye.

PMID- 9558841
TI  - [Aqueous levels of eosinophil cationic protein and major basic protein in
      patients with retinal detachment associated with atopic dermatitis].
AB  - We measured the aqueous levels of eosinophil cationic protein (ECP) and major
      basic protein (MBP) to investigate a possible relationship between cytotoxic
      eosinophil granule proteins and retinal detachment (RD) in patients with atopic
      dermatitis. While aqueous ECP was detected in only 1 of 15 cases of RD associated
      with atopic dermatitis, aqueous MBP was detected in 6 of 14 cases (42.9%). 11
      cases of RD without atopic dermatitis were also studied, but neither ECP nor MBP
      was detected. Although the role of aqueous ECP and MBP was not elucidated, the
      results indicate that cytotoxic eosinophil granule proteins, especially MBP, are
      present in aqueous humor in certain cases of RD associated with atopic
      dermatitis.

PMID- 9558843
TI  - [Neovascularization from the scleral wound as the cause of vitreous rebleeding
      after vitrectomy for proliferative diabetic retinopathy].
AB  - Vitreous hemorrhage recurred in 11 eyes out of a series of 120 eyes treated by
      vitrectomy for proliferative diabetic retinopathy during a 10-month period.
      Neovascularization from the scleral wound, or fibrovascular proliferation, was
      identified as the cause of rebleeding in 4 eyes from findings during
      revitrectomy. None of the 4 eyes showed retinal disorders attributable as the
      cause of rebleeding. Rebleeding in these 4 eyes developed after an average of 9.0
      weeks after initial surgery. The proliferative membrane was oval in shape and
      expanded from the residual vitreous which had been incarcerated in the scleral
      wound. The proliferative membrane obtained during revitrectomy was poor in
      cellular components and contained extracellular matrix. Blood vessels of various
      sizes were also present. Electron microscopically, the membrane was rich in
      extracellular components. It contained two types of cells, i.e., high and low
      electron density cells. These cells often had microvilli and seemed to be of
      epithelial origin. The findings show that vitreous rebleeding may develop from
      fibrovascular proliferation from the scleral wound after diabetic vitrectomy. The
      proliferated membrane showed histological similarities with the fibrovascular
      proliferation usually seen in the diabetic retina and may represent a type of
      anterior proliferation secondary to retinal ischemia.

PMID- 9558844
TI  - [Characteristics of retinal detachment in eyes with choroidal colobomas].
AB  - We reviewed 6 eyes of 6 patients (1 male and 5 females) with retinal detachment
      associated with choroidal coloboma. Three of these 6 eyes had visible retinal
      breaks within or at the margin of the coloboma. In one eye, no retinal breaks
      were noted before or during vitreous surgery, and shallow retinal detachment was
      localized in the posterior fundus. One eye with bullous retinal detachment with
      retinal breaks within the coloboma had been having serous retinal detachment
      localized in the nasal area close to the optic nerve head. In all of these five
      eyes; vitrectomy, relaxing retinotomy inside the coloboma close to its edges, and
      cyanoacrylate retinopexy resulted in successful reattachment of the retina.
      Schisis-like separation similar to that in pit-macular syndrome was noted in the
      posterior retinal in one eye which had no visible retinal break. Non
      rhegmatogenous retinal detachment may exist in association with choroidal
      colobomas.

PMID- 9558845
TI  - [Chorioretinal malformation in vascular loop formation on the optic disc].
AB  - We have studied the eyes of a 57 year-old man, with good visual acuity, who was
      found to have an unusual prepapillary vascular loop formation in both eyes.
      Ophthalmoscopic examination revealed that the central retinal vein ran a course
      beneath the retinal pigment epithelium in right eye. Fluorescein angiography
      showed the prepapillary vascular loops to originate from the central retinal
      artery in both eyes. We also noted arterial, but not arteriovenous, shunt
      formation in the retina of both eyes. By indocyanine green angiography we
      demonstrated the presence of a drainage system, the so called posterior ciliary
      vein, which was connected directly to the central retinal vein temporal to the
      optic disc in the right eye. We believe this to be a new type of chorioretinal
      vascular formation which is different from the chorio-vaginal vein and the optico
      ciliary vein.

PMID- 9558846
TI  - [Studies on utility of MR T2-weighted images using multishot echo-planar imaging
      for hepatic mass lesions].
AB  - MR T2-weighted images using multishot echo-planar imaging (EPI) and fast spin
      echo (FSE) sequences were obtained in 22 patients with hepatic masses. Multishot
      EPI sequences included eight-shot breath-hold EPI and 16-shot EPI without breath
      hold, while FSE sequences included nonfat-suppressed respiratory-triggered FSE,
      fat-suppressed respiratory-triggered FSE, and nonfat-suppressed breath-hold FSE.
      Signal-to-noise ratio, contrast-to-noise ratio and artifacts were compared
      between EPI and FSE images of 47 hepatic masses. In evaluating solid tumors, EPI
      provided image quality equal or superior to that of FSE, whereas in the
      evaluation of nonsolid tumors FSE showed better image quality than EPI. In
      conclusion, it was demonstrated that in the evaluation of hepatic solid tumors T2
      weighted eight-shot breath-hold EPI can replace both nonfat-suppressed
      respiratory-triggered FSE and breath-hold FSE, and it was suggested that eight
      shot breath-hold EPI can replace fat-suppressed respiratory-triggered FSE to
      reduce patient discomfort and increase examination throughput.

PMID- 9558847
TI  - [Results of radiation therapy for limited small-cell lung cancer].
AB  - Results of radiotherapy were reviewed in 68 patients with limited small-cell lung
      cancer from the aspect of local control. Thirty-one patients achieved CR (46%),
      while the other 31 remained at PR. The 1-, 2-, 3-, and 5-year cumulative survival
      rates were 57%, 28%, 21%, and 16%, respectively, for 15 months in MST. Thirty-six
      patients developed local recurrence (53%) and 46 had distant metastasis (68%).
      The thirty-one patients with CR had a 43% 2-year-survival rate and 23 months in
      MST. The remaining 37 patients (PR + NC) had respective figures of 13% and 13
      months (p < 0.025). There was no statistically significant difference between
      radiation dose and local thoracic failure among the patients. Of the 31 patients
      with CR, 28 had achieved CR at 45Gy (17 received 55Gy or more, and 11 less than
      55Gy). In the former, the local control rate, 2-year-survival and MST were 94%,
      53% and 44 months, while in the latter these were 45%, 27% and 17 months,
      respectively. Thirty-five patients were irradiated by the shrinking field
      technique according to tumor reduction; however, this technique did not influence
      the treatment results. To obtain better results, it is first necessary to achieve
      CR at initial chemo-radiotherapy. As to irradiation, randomized trials between
      50Gy and 60Gy would require patients with CR at 45Gy.

PMID- 9558848
TI  - [C-MOS flat-panel sensor for real time X-ray imaging].
AB  - Flat-panel, self-scanning, solid state diagnostic x-ray imaging devices using
      complementary metal-oxide-semiconductor (C-MOS) arrays are under investigation. A
      unit device with a 5 cm by 5 cm sensor area was developed and tested. The device
      consists of a CsI scintillator and C-MOS detector arrays. The detector arrays are
      composed of a regular arrangement of pixels (256 x 256), each of which is made of
      a C-MOS photodiode sensor coupled to a C-MOS FET (field effect transistor). A
      common FET gate line is connected to all the FET gates along each column. A
      common date line is connected to all the FET drains of each row. The source
      contact of each FET is connected to that of its corresponding photodiode. A
      positive gate pulse applied to a gate turns on all FETs connected to the date
      lines. The readout continues column by column. Correlated double sampling
      circuits and an offset variance compensation circuit were installed to reduce
      noise. A sampling speed of 15 frames per second and spatial resolution of 2.5
      line per mm were achieved. Noise level and maximum signal were 1.5 mV rms and 1.8
      V, respectively. Image quality was considered acceptable for clinical use. It is
      also discussed how to fabricate a large area sensor with the unit device.

PMID- 9558849
TI  - [Is medical linac suitable for high-precision stereotactic irradiation?:
      investigations in geometrical accuracies of gantry and couch].
AB  - Linac-based radiosurgery has many advantages over the gamma knife, including low
      initial cost and no need of source replacement. On the other hand, most of the
      medical linacs currently in use were not originally designed to be applied for
      radiosurgery, and, therefore, careful quality assurance programs are required. In
      the gantry-head of a linac, a small CCD video camera is mounted in a position
      optically identical to that of the x-ray source. The video signal from the camera
      was digitalized to be evaluated for geometrical errors. A metal ball fixed to the
      stereotactic base frame via XYZ-sliding rods was used as a simulated target.
      Displacements of the target from the isocenter were measured during rotation of
      the gantry. Displacements in the gantry-rotation plane were satisfactorily small,
      while those perpendicular to it were maximal at gantry position angles of 0
      degree and 180 degrees. This error night be caused by gravitational vending of
      the heavy gantry head. Although other major errors of the linac were within one
      millimeter, the center of coach rotation around the isocenter did not coincide
      with the center of gantry rotation, probably owing to gravitational vending.
      Special care should be taken when very small collimators are employed.

PMID- 9558850
TI  - [Placing two parallel catheters by Seldinger's approach through the femoral
      artery for CT angiography and CT during arterioportography: evaluation of
      efficacy and safety].
AB  - The purpose of this study was to evaluate the efficacy and safety of placing two
      parallel catheters by Seldinger's approach through the femoral artery for CT
      angiography (CTA) and CT during arterioportography (CTAP). We performed an
      analysis of 30 patients. Two introducers were successfully placed in all cases.
      Only one minor complication was observed, a localized inguinal hematoma. The
      CTA/CTAP procedures were successful in all patients except six who had anatomical
      variations of the hepatic arterial supply. Our methods proved to be useful and
      safe for patients with standard hepatic arterial supply.

PMID- 9558851
TI  - [New methods for measuring atlanto-axial vertical subluxation in rheumatoid
      arthritis by MR imaging].
AB  - We proposed two new methods of measuring atlanto-axial vertical dislocation in
      rheumatoid arthritis by MR imaging. One is the distance from the subdental
      synchondrosis of the axis to the diameter of the ring of the atlas. The other is
      the distance from the midpoint of the anteroposterior ends of the inferior margin
      of the axis to the diameter of the ring of the atlas. Values were also determined
      by the Ranawat method and the Redlund-Johnell method. There was good correlation
      between values determined by the new methods and those determined by the Ranawat
      method and Redlund-Johnell method.

PMID- 9558852
TI  - [Three-dimensional MR angiography of HCC and portal and hepatic veins using
      superparamagnetic iron oxide].
AB  - We examined a new MR technique for obtaining 3D-MRA images of the liver that
      simultaneously depicts HCC and the portal and hepatic veins. Five patients with
      clinically suspected HCC were studied with superparamagnetic iron oxide (SHU
      555A) used as a negative contrast medium for the liver. In our study, a 3D
      rotational display was provided on the CTR monitor from 2D-TOF images by computed
      reconstruction, clearly showing HCC and portal and hepatic veins on the same
      image. Our method was found to be of great value in planning surgery of the
      liver.

PMID- 9558853
TI  - [Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using
      spectrally selected enhanced fast gradient recall sequence].
AB  - Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using the
      spectrally selected enhanced fast gradient recall sequence (spec IR-efgre3d) was
      performed in five patients with HCC. Ten HCC nodules were confirmed by CTA, CTAP
      and Lipiodol CT, and all of them were detected with dynamic MRI. MIP images
      reconstructed from 3D gadolinium-enhanced dynamic MR studies clearly showed the
      main portal vein and its branches in all cases. Portal vein thrombosis was also
      demonstrated with the MIP images.

PMID- 9558854
TI  - Obstruction of the right ventricle outflow tract during right cardiac prolapse.
AB  - We observed cardiac prolapse following right pneumonectomy in which the patient
      experienced a 90 degree rotation of the heart and compression of right
      ventricular outflow tract from behind by the aorta, which led to an increase in
      right atrial pressure and a decrease of pulmonary artery pressure and cardiac
      output. Compression of the right ventricular outflow tract by the base of the
      aorta was observed as an additional shock inducing factor in right cardiac
      prolapse.

PMID- 9558855
TI  - The double fold free radial forearm flap for skin large fistule closure after
      pharyngoesophageal operation.
AB  - Reported herein is a case who underwent a one-stage closure of pharyngostome
      utilizing a double fold free radial forearm flap (FRF) was performed. By use of a
      thin and large FRF, this operative method permits the closure of a large fistula
      and thus satisfies cosmetic requirements.

PMID- 9558856
TI  - [Open heart surgery without blood transfusion for cyanotic congenital cardiac
      defects].
AB  - Between November 1994 and January 1997, 42 cases of cyanotic congenital cardiac
      defects underwent definitive surgery at Matsudo Municipal Hospital. We evaluated
      30 cases, each weighing from 7 to 20 kg. The procedures were performed at the age
      of 9 months to 6 years (mean age-2.4 years). The body weights were 7.7 to 20 kg
      (mean weight-11.4 kg). The preoperative diagnoses were Tetralogy of Fallot (TOF)
      in 19 cases, Fontan candidates in 6 and the others in 5. We classified them into
      3 groups; Group A--15 cases were completed with non-blood transfusion, Group B--8
      cases used only plasma protein fraction and Group C--7 cases used blood
      transfusion. Cardiopulmonary bypass (CPB) system is a semi-closed circuit and
      priming volume is 400 to 600 ml. There is no difference among the 3 groups in
      operative age, body weight, operation time, CPB time, aortic cross clamp time,
      bleeding and postoperative state. The same results were obtained in minimum base
      excess and urine output during CPB and the changes of hematocrit and total
      protein. In Groups A and B, CPB blood was returned to the patient as soon as
      possible after CPB was weaned, but in Group C, blood transfusion was performed
      without the return of CPB blood. In all groups, hemodynamics were stable.
      Retrospectively, it is thought that blood transfusion was not necessary in Group
      C and the use of the plasma protein fraction was not needed in Group B. In
      conclusion, the open heart surgery can be performed safely without blood
      transfusion for cyanotic congenital cardiac defects.

PMID- 9558857
TI  - [Postoperative complications after coronary bypass operations in patients with
      pulmonary impairment].
AB  - The postoperative courses of 112 patients with pulmonary disease (59 with
      obstructive disease = Group 0, 38 with restrictive disease = Group R and 15 with
      mixed disease = Group M) who underwent elective coronary artery bypass grafting
      were retrospectively reviewed. Preoperative pulmonary function test (percentage
      of vital capacity = %VC and percentage of forced expiratory volume at 1 second =
      FEV1.0%) of these group showed typical abnormal values, and velocity ratio of 50%
      and 25% of maximum expiratory flow volume (V50/V25) of each groups were measured
      abnormal values (3.99 +/- 1.44 of Group O, 4.26 +/- 1.42 of Group R and 3.74 +/-
      1.82 of Group M). The our strategy for these groups were a). Using
      skeletonization method for harvesting internal mammary artery (IMA) b) Take care
      not to injure the phrenic nerve and open the pleural cavity as surgical
      techniques (Harvesting IMA) and c) Administration of theophylline derivatives and
      corticosteroids to prevent bronchospasm d) Administration of concentrated serum
      albumin and diuretics to prevent pulmonary edema as therapeutic measures. The
      length of stay in the intensive care unit and ventilation time of each groups
      were not significantly longer. Patients of group M had more respiratory
      complications (atelectasis, pleural effusion, pneumothrax, bronchospasm, and
      pneumonia) than did patients of group R (p < 0.05), but did not more nonpulmonary
      complications and hospital deaths. The four in hospital deaths (2 with group O, 1
      with group R and 1 with group M) were not directly related to pulmonary
      complications. Thus, result of CABG in patients with pulmonary impairment
      definitely proved to be satisfactory by our strategy, but mixed pulmonary
      diseased significantly had more pulmonary complications.

PMID- 9558858
TI  - [Mid-term evaluation of cryopreserved aortic allograft].
AB  - Recently aortic root replacement and free-hand aortic valve replacement with
      cryopreserved allograft are accepted and established as useful procedures in USA
      and Europe. Otherwise allograft aortic valve failure due to structural valve
      degeneration, progressive loss of leaflet extensibility or progressive aortic
      root dilatation are reported. Aortic root replacement and free-hand aortic valve
      replacement with cryopreserved allograft were performed on three patients in the
      Department of Cardiovascular Surgery, NCVC between March of 1992 and March of
      1994. We evaluated the mid-term function of implanted allograft. Case 1, 2, 58
      year-old male and 42-year-old male with aortic regurgitation due to Aortitis had
      modified Bentall procedures with composite graft and had redo surgery for aortic
      regurgitation due to graft detachment with cryopreserved allograft using "aortic
      root replacement". Case 3: 54-year-old male received a cryopreserved allograft
      for aortic stenosis/regurgitation using "free-hand technique". Postoperative
      echocardiogram showed excellent valve function without regurgitation any
      calcification in all cases. However chest computed tomography suggested the new
      calcification of allograft wall at 15 months after operation in Case 1 who was
      administered steroid agents, despite no calcification in Case 2 during 17 months
      follow-up.

PMID- 9558859
TI  - [An analysis of the mechanism of postoperative hyperbilirubinemia following
      resection of thoracic esophageal cancer in terms of hepatic venous oxygen
      saturation and excessive systemic reactions].
AB  - Hepatic venous oxygen saturation (ShvO2), parameters of systemic circulation and
      cytokine (Interleukin 6) (IL-6)) level were measured in 21 patients with thoracic
      esophageal cancer in order to analyze the mechanism of occurrence of
      postoperative hyperbilirubinemia (PHB). ShvO2 fell during operation, especially
      during intrathoracic procedures, and a significant correlation was noted between
      the total time during which ShvO2 was below 60% and the postoperative peak serum
      bilirubin level (peak-Bil) (r = 0.595, p = 0.0037). Patients with PHB (group H)
      had worse systemic circulation and a lower oxygen supply postoperatively than
      patients without PHB (group N). Body weight and water balance recovered earlier
      in group N. Postoperatively, numbers of peripheral lymphocytes and platelets
      changed lower in group H, while CRP and IL-6 changed higher in group H.
      Furthermore, a significant correlation was noted between the IL-6 level just
      after operation and peak-Bil (r = 0.669, p = 0.0006). These results suggests PHB
      results from intraoperative liver hypoxia and poor postoperative systemic
      circulation. Individual severeness of reactions to the operative stress,
      excessive or adequate, plays a role in the occurrence of PHB as well.

PMID- 9558860
TI  - [Clinical benefits of normothermic cardiopulmonary bypass on postoperative
      systemic metabolism].
AB  - To evaluate the influence of body temperature during cardiopulmonary bypass (CPB)
      on postoperative systemic metabolism, 32 patients undergoing elective cardiac
      surgery were randomly assigned to either hypothermia (n = 16) or normothermia (n
      = 16). Serial hemodynamic parameters and blood samples were obtained after
      surgery. CPB and operation times were significantly shorter and the platelet
      reduction ratio during CPB [ = (platelets before CPB-platelets after
      CPB)/platelets before CPB] was significantly lower in normothermic patients than
      in hypothermic patients. The platelet reduction ratio was dependent on the
      minimum rectal temperature during CPB, the operation time, and the CPB time. In
      the early postoperative period, hypothermic patients had abnormally high systemic
      vascular resistance and a reduced cardiac index compared with the normothermic
      patients. There were no differences between 2 groups in postoperative hepatic and
      renal functions, changes in oxygen consumption, arterial-venous PCO2 or arterial
      venous pH gradient. This study suggested a beneficial influence of normothermic
      CPB on postoperative hemodynamics. Normothermic CPB was not associated with
      adverse effects on postoperative metabolic recovery.

PMID- 9558861
TI  - [Postoperative infections related to pacing wires, pulmonary arterial catheters,
      and drainage tubes temporarily inserted during open-heart surgery].
AB  - Bacterial examinations of temporary pacing wires (P-wires), pulmonary arterial (P
      A) catheters, and drainage tubes temporarily inserted during open-heart surgery
      were performed in 213 patients. Bacteria were detected in 19 (2.8%) of 672
      specimens gathered from the subject patients, with coagulase-negative
      Staphylococcus (CNS) being most frequently observed. P-wires accounted for 17 out
      of 19 of the culture-positive specimens, and 7 of the P-wires remained in place
      for more than two weeks. The frequency of infection with the P-wires was
      significantly higher than with the P-A catheters or drainage tubes. The period of
      time that the P-wire was left in place significantly longer than for P-A catheter
      or drainage tube. There was, however, no statistically significant difference
      between the culture-positive and negative groups in respect to age, detention
      periods, operation times, CPB times, or length of ICU stay. As a result of these
      findings, we have concluded that P-wires should be removed as soon as possible
      following surgery, and in any case, a meticulous care should be taken to prevent
      transcutaneous infection.

PMID- 9558862
TI  - [Mediastinoscopic drainage for descending necrotizing mediastinitis].
AB  - A case of descending necrotizing mediastinitis that was treated by
      mediastinoscopic drainage is reported. The patient was a 56-year-old diabetic
      woman. A hypopharyngeal abscess extended to the mediastinum through the neck. No
      septic condition was noted. Chest CT showed that the abscess reached 4 cm below
      the tracheal bifurcation. Pus was drained under direct observation by
      mediastinoscopy, and a drain was placed in an appropriate position. After
      operation, lavage was performed through the drain, and cure was achieved on the
      42nd postoperative day. This technique should be considered as surgical treatment
      for descending necrotizing mediastinitis in the absence of serious complication
      such as sepsis, because it has a more reliable drainage effect than the
      conventional transcervical method, and because it is less invasive than
      thoracotomy.

PMID- 9558863
TI  - [Transcatheter stent-graft implantation for the treatment of acute aortic
      dissection--rupture of aneurysm because of perigraft leakage].
AB  - An 82-year-old woman was diagnosed as having acute type B aortic dissection. At
      bed rest, her systolic blood pressure was kept less than 120 mmHg. Four days
      later the aneurysm threatened to rupture. Because she presented a high operative
      risk for open-chest surgery, a stent-graft was implanted across the dissection
      site via transcatheter. The entry site to the aneurysm was closed by the stent
      graft, and postoperative aortograph demonstrated that contrast medium did not
      enter the false lumen except for a trivial projection. A CT scan 6 days after the
      stent-graft implantation unexpectedly demonstrated the false lumen not only had
      not thrombosed, but had expanded. As a result, 8 days after the operation the
      aneurysm ruptured into the left pleural cavity, and the patient died. An autopsy
      revealed the stent-graft was exactly implanted across the entry site, but that
      the diameter of the graft was slightly larger than that of the aorta.
      Consequently, a portion of the rim of the graft had been wraped after
      implantation, causing perigraft leakage. Leakage is one of the gravest
      complications of the stent-graft implantation, to prevent it, a new design for
      stent-graft device is essential.

PMID- 9558864
TI  - [The usefulness of thoracoscopic surgery for pleuritis carcinomatosa].
AB  - We performed thoracoscopic surgery for pleuritis carcinomatosa, in which re
      expansion of the collapsed lung was impossible, by employing tube thoracostomy.
      One of the treatments used for pleuritis carcinomatosa was drainage of the
      pleural effusion followed by re-expansion of the collapsed lung. The
      decortication and biopsy of the pleura and the pleural effusion drainage with the
      thoracoscopic procedure were performed, allowing control of the pleural effusion
      and re-expansion of the collapsed lung to be accomplished. We conclude that
      thoracoscopic surgery is useful for the thoracic treatment of pleuritis
      carcinomatosa.

PMID- 9558866
TI  - [A case of Pryce type I intrapulmonary sequestration].
AB  - A twenty-year-old asymptomatic man hospitalized because of a vascular murmur and
      abnormal shadow in the left lower lung on X-ray film. An aortogram revealed an
      abnormal artery arising from the descending thoracic aorta and supplying the left
      basal segment, which had no other pulmonary arteries. Although lung ventilation
      scintigraphy demonstrated reduced ventilation to the left lower lobe, bronchogram
      showed an almost normal bronchial tree except that peripheral branches were
      slightly thin. A clinical diagnosis of Pryce type I intrapulmonary sequestration
      was made, and left lower lobectomy was performed successfully. We have analyzed
      31 cases of Pryce type I intrapulmonary sequestration in Japan. A vascular murmur
      is often heard, and a chest X-ray usually shows either a mass shadow or increased
      vascular markings. In most of those cases, an abnormal artery arises from the
      descending thoracic aorta and it supplies the left basal segment. Because this
      type of sequestration causes hemoptysis and infections, surgical intervention is
      indicated.

PMID- 9558865
TI  - [A case of graft replacement of the ascending aorta to the aortic arch and the
      partial descending aorta in a single stage for thrombosed aortic dissection
      (DeBakey type II + IIIb)].
AB  - We report here a case of graft replacement of the ascending aorta to the aortic
      arch and the middle portion of the descending aorta in a single stage for
      thrombosed aortic dissection. The patient was a 53-year-old male who was
      transferred to our hospital with a diagnosis of thrombosed aortic dissection.
      Conservative therapy was continued but three weeks after the onset, chest
      enhanced CT scan and digital subtraction angiography revealed an opacified false
      lumen in the ascending aorta and a ulcer like projection in the middle portion of
      the descending aorta. He was therefore diagnosed as having redissecction in
      DeBakey type II + IIIb thrombosed aortic dissection. Graft replacement of the
      ascending aorta, the aortic arch, and a part of the descending aorta was
      performed in a single stage via median stenotomy with the aid of extracorporeal
      circulation and selective cerebral perfusion. Postoperative digital subtraction
      angiography showed satisfactory reconstruction of the thoracic aorta. The patient
      is still leading a normal life two years after the operation.

PMID- 9558867
TI  - [An emergent operation for metastatic cardiac tumor of malignant cystosarcoma
      phyllodes].
AB  - A 47-year-old woman was transferred to our hospital under endotracheal intubation
      with severe hemodynamic deterioration. A left mastectomy had been performed 8
      months earlier and histology of the specimen showed malignant cystosarcoma
      phyllodes. An angiography and echocardiography suggested massive mass of the
      right ventricle extending to the pulmonary artery. An emergent life-saving
      operation was required using cardiopulmonary bypass. A huge multilobular tumor
      was resected from the right ventricle through the pulmonary artery as much as
      possible and a tricuspid valvuloplasty was also performed. The patient was weaned
      from cardiopulmonary bypass, then satisfactorily recovered from hemodynamic
      disturbances. Nevertheless, she died 15 days later due to multiple organ failure.
      Microscopic examination of resected specimen showed the neoplastic stromal cells
      that increase mitotic activity and have sarcomatous characteristics, consistent
      with a metastatic cystosarcoma phyllodes. This is a second case of operation for
      cardiac metastasis of cystosarcoma phyllodes using cardiopulmonary bypass, so far
      presented in the literature of the world reviewed by the authors.

PMID- 9558868
TI  - [Cystic thymoma without solid mass lesions on diagnostic imaging--a case report].
AB  - A 68-year-old man was referred to our hospital because of an abnormal shadow on a
      chest X-ray film. A chest CT scan and MRI demonstrated a cystic mass without
      solid lesions on the anterior mediastinum. The CT scan also showed that it was a
      well-defined and homogenous mass without contrast enhancement effect. 67Ga and
      201T1 scintigrams showed no uptake in the mass. Needle aspiration cytology was
      performed, and there was no evidence of neoplasms. A thymic cyst was diagnosed,
      and then an operation was performed. At the operation, the cystic tumor was
      removed along with thymic tissues by a median sternotomy. On the cut section of
      the resected specimen, the tumor was found to be a cyst with small solid nodules
      on the wall. Pathologic examination revealed that the tumor was a cystic thymoma.
      We consider that patients with cystic tumors on the anterior mediastinum should
      obtain histopathologic diagnosis because of the difficulty in excluding neoplasms
      such as thymoma.

PMID- 9558869
TI  - [Malignant fibrous histiocytoma of the diaphragm--a case report].
AB  - A 56-year-old woman was admitted to our hospital with the chief complaint of left
      back pain. We detected left pleural effusion on chest X-ray and performed chest
      drainage. No malignant cells were detected in the effusion. Chest CT demonstrated
      a tumor shadow over the left diaphragm and left pleural effusion 6 months later.
      She underwent en bloc resection of the tumor and left diaphragm. Histological
      evaluation revealed malignant fibrous histiocytoma (MFH). Recurrent tumors were
      found in the abdomen 8 months after the operation, and she underwent resection of
      the abdominal recurrent tumors. Histological evaluation of the recurrent tumors
      also showed MFH. The patient died 28 months after the first operation.

PMID- 9558870
TI  - [Combined rupture of trachea and esophagus following blunt trauma--a case
      report].
AB  - A 49-year-old man was involved in a motor vehicle crash and was admitted to a
      local hospital. The following day, he was transferred to our hospital because of
      worsening dyspnea. Initial examination revealed no subcutaneous emphysema, and
      chest computed tomography (CT) demonstrated no mediastinal air. A left
      thoracentesis tube was placed for pneumothorax, which reduced the patient's
      respiratory distress. He had a persistent, productive cough, which worsened when
      he drank water. A repeat chest CT on the fifth hospital day revealed a tracheo
      esophageal fistula. Bronchoscopy and esophagoscopy confirmed the diagnosis. He
      underwent repair of the trachea and esophagus. The ruptured membraneous portion
      of the trachea was closed with interrupted sutures and covered with pedicled
      pericardial flap. The perforated anterior esophageal wall was sutured in layers
      and reinforced with a fifth intercostal muscle flap. A gastrostomy tuve was
      placed for feeding access. Within 6 weeks, the patient recovered completely.

PMID- 9558871
TI  - [Left atrial isolation for chronic atrial fibrillation associated with aortic
      arch dissection and aortic valve disease in a 70-year-old man].
AB  - A 70-year-old male with aortic regurgitation, chronic atrial fibrillation (Af)
      and chronic aortic dissection of the aortic arch was treated simultaneously. We
      found a limited dissection in front of aortic arch during operation. We performed
      total arch replacement using a branched prosthesis and aortic valve replacement
      in addition to a modified left atrial isolation for chronic Af under the aid of
      extracorporeal circulation, and selective cerebral perfusion. Left atrial
      isolation is a simpler procedure than maze procedure and left side maze procedure
      for eliminating Af. This simple procedure makes possible a simultaneous extended
      operation for complicated aortic and cardiac disease even in an elderly patient.

PMID- 9558872
TI  - [Huge localized mesothelioma of the diaphragm in a 17-year-old female--a case
      report with calculated tumor volume doubling time].
AB  - An operative case of localized mesothelioma of the pleura developed in a 17-year
      old female was reported. She was admitted to our hospital complaining of right
      chest pain. A chest X-ray film showed a huge mass in the right lower field of the
      lung. After the embolization of the right inferior phrenic artery, which was the
      main feeder to the tumor, it was then successfully resected combined with the
      right diaphragm and the right lower lobe of the lung. Histologically, the tumor
      was diagnosed as benign localized mesothelioma (solitary fibrous tumor of the
      pleura). Further histological and immunohistochemical study revealed that it had
      developed from the connective tissue under the parietal mesothelium of the
      diaphragm. As chest roentgenograms had been undertaken during past two years, the
      tumor volume doubling time was calculated at 153 days. Despite the short tumor
      volume doubling time as like primary lung cancer, she is alive without recurrence
      5 years after the operation.

PMID- 9558873
TI  - [A case of ruptured descending thoracic aortic aneurysm due to Salmonella
      infection].
AB  - A 66-year-old male was admitted to our hospital because of pyrexia, chest pain
      and hemosptum. Inflammatory findings were made and salmonella enteritidis was
      detected by bacterial examination of sputum and stool. Enhanced chest CT
      examination disclosed a descending thoracic aortic aneurysm which had ruptured
      into the left lower lobe of the lung. Under a diagnosis of ruptured mycotic
      descending thoracic aortic aneurysm, an emergency operation was performed. A left
      posterolateral thoracotomy carried out after axillo-bilateral femoral bypass
      grafting. A pseudoaneurysm of the descending thoracic aorta had ruptured into the
      left lower lobe of the lung. After resection of the aneurysm, closure of both
      ends of the intact descending thoracic aorta and a left lower lobectomy were
      carried out. An ascending aorta-infrarenal abdominal aorta bypass was performed
      because of insufficient visceral arterial blood flow through the axillo-bilateral
      femoral bypass. The patient's immediate postoperative recovery was complicated by
      paraplegia. Chloramphenicol and levofloxacin were administered for three months,
      after which his recovery followed a good course.

PMID- 9558874
TI  - [Initial clinical experiences of the ABIOMED BVS SYSTEM 5000 in Japan].
AB  - The initial clinical experience of the ABIOMED BVS SYSTEM 5000 in Japan is
      reported. The system is a paracorporeal pulsatile assist device intended for
      temporary ventricular support. It consists of a pneumatic drive console, a blood
      pump, and the atrial and arterial cannulas. The pump is of a dual chamber design,
      with the upper chamber as a passive, gravity filled resevoir and the lower
      chamber as a pumping chamber. Since the system is designed to be simple, safe and
      automatically controlled, no additional personnel is required to control
      perfusion. This report describes our initial clinical experiences with the
      ABIOMED BVS SYSTEM 5000 in Japan. This device was used in three patients with
      post cardiotomy cardiogenic shock and fulminant myocarditis. The first patient
      developed acute occlusion of left main coronary artery who required emergent
      surgical revascularization following PTCA and stent implantation. He couldn't
      wean from CPB and required the insertion of an LVAD. The second case suffered
      from a cardiac arrest after CABG and could not be resuscitated. The ABIOMED BVS
      5000 was inserted and the patient successfully weaned from support. The third
      patient developed fulminant myocarditis and was supported with the system for 269
      hours and was successfully weaned after near complete myocardial recovery. Our
      initial experience with the ABIOMED BVS SYSTEM 5000 indicates that the system can
      provide complete cardiac support allowing full recovery from a cardiac variety of
      causes of dysfunction. The device has the potential to improve the survival rate
      of patients with severe acute recoverable myocardial damage. It is expected that
      this device can be a viable tool for treatment of intractable heart diseases.

PMID- 9558875
TI  - [Two surgical cases of right parasternal minimal incision for aortic valve
      replacement].
AB  - Although median sternotomy has been used as a good approach to all cardiac valves
      and coronary arteries, advantages of the minimal invasive cardiac operation have
      been reported recently. We employed the right parasternal minial incision,
      reported by Cosgrove et al. for two cases of aortic valve replacement. In the
      first case, we were able to get a good operation field and easily implanted a
      mechanical prosthesis. In contrast, we had some difficulties with the second case
      where in addition to the third and fourth cartilages, a second cartilage
      resection was necessary because the aortic root lay at a cephalic level.
      Moreover, the operation field was restricted because we left several rib
      cartilages to preserve the right internal thoracic artery. The cannula had to be
      inserted via the right atrium as we failed to insert it in the right femoral
      vein, and the aortic root deviated more medially than usual. From these
      experiences, it is important to check the position of aortic root, and if the
      cannula cannot be inserted in the femoral vein, cannulation via the right atrium
      can ve utilized in the minimal invasive cardiac operation.

PMID- 9558876
TI  - [Clinical significance of hepatitis G virus (GBV-C/HGV)].

PMID- 9558877
TI  - [The clinical significance of plasma tissue plasminogen activator (t-PA) levels
      in severe acute or fulminant hepatitis].
AB  - We studied the tissue plasminogen activator (t-PA) levels in the plasma of
      patients with acute hepatitis (AH), severe acute hepatitis (AHs) and fulminant
      hepatitis (FH). Plasma t-PA levels were measured consecutively on the first,
      third and seventh days of hospitalization. Plasma t-PA levels were markedly
      higher in AHs and FH than in AH (p < 0.05, p < 0.01, respectively) on the first
      day, but did not differ significantly between AHs and FH on this day. The t-PA
      levels decreased markedly on the third and seventh days in AHs (both p < 0.05),
      but did not change from the first day to the third and seventh days in FH. The t
      PA levels on the third and seventh days were higher in FH than in AHs (both p <
      0.05). There was a significant increase in the plasma t-PA level before an
      episode of encephalopathy in FH compared with levels in AHs. These observations
      suggest that t-PA level may be useful as a prognostic parameter in patients with
      acute hepatic injury.

PMID- 9558878
TI  - [Transjugular intrahepatic portosystemic shunt for the treatment of refractory
      ascites].
AB  - Five cirrhotic patients with refractory ascites were treated with transjugular
      intrahepatic portosystemic shunt (TIPS). Before TIPS, although patients were
      received salt restriction (5 g/day), diuretic therapy (furosemide 112 mg/day,
      spironolactone 140 mg/day), albumin infusion and paracentesis, ascites did not
      show improvement. After TIPS, urine volume and urinary sodium excretion increased
      significantly. Mean body weight decreased significantly from 73 kg before TIPS to
      63 kg a month after TIPS. Improvement of ascites after TIPS were associated with
      a significant reduction in the dose of diuretics. On discharge, complete
      resolution of ascites was found in 2 patients and mild ascites remained in 3
      other patients. Four patients presented 6 episodes of shunt stenosis in the
      follow-up period, and were treated with balloon dilatation. Ascites increased on
      shunt dysfunction and showed improvement after balloon dilatation. Post-TIPS
      encephalopathy was seen in 2 patients and one of 2 was disabled. In conclusion,
      although post-TIPS shunt dysfunction and encephalopathy are common. TIPS is an
      effective therapy for refractory ascites in patients with cirrhosis.

PMID- 9558879
TI  - [A case of pyogenic granuloma in the cervical esophagus].

PMID- 9558880
TI  - [A case report of gastric leiomyosarcoma developed at the fornix prolapsed into
      the duodenum].

PMID- 9558881
TI  - [Effect of drainage and injection factor XIII with fibrinogen for hepatic biloma
      resulting from transcatheter arterial embolization in patients with
      hepatocellular carcinoma--report of two cases].

PMID- 9558883
TI  - [Two cases of Castleman's disease originated in the retroperitoneum].

PMID- 9558882
TI  - [A case of anticonvulsive drug-induced liver injury accompanied by a transient
      appearance of antimitochondrial antibody, M2].

PMID- 9558884
TI  - Alternative medicine: readers have their say.

PMID- 9558885
TI  - Alternative medicine: readers have their say.

PMID- 9558886
TI  - Alternative medicine: readers have their say.

PMID- 9558887
TI  - Alternative medicine: readers have their say.

PMID- 9558888
TI  - Psoas abscess: an uncommon disease.

PMID- 9558889
TI  - Hogs and health.

PMID- 9558890
TI  - An open letter to North Carolina doctors: Wall Street mentality and health care-
      a poison pill?

PMID- 9558891
TI  - Coccidioidomycosis in a patient with atopic dermatitis.

PMID- 9558892
TI  - Colocutaneous fistula. A rare complication of percutaneous gastrostomy.

PMID- 9558893
TI  - Bloody diarrhea caused by Escherichia coli O157:H7.

PMID- 9558894
TI  - Niacin. Help for your cholesterol--harm for your liver.

PMID- 9558895
TI  - How does North Carolina law enforcement limit youth access to tobacco products? A
      study of officers' attitudes and behaviors.

PMID- 9558896
TI  - The role of the medical profession in a managed care environment. Statement of
      the Bioethics Committee of the North Carolina Medical Society.

PMID- 9558897
TI  - "Cage" technology revolutionizes approach to spinal fusion surgery.

PMID- 9558899
TI  - A program to control breast and cervical cancer in North Carolina.

PMID- 9558898
TI  - How do North Carolina prenatal care providers counsel and test pregnant women for
      HIV? Survey measures knowledge of HIV testing benefits.

PMID- 9558900
TI  - Response to a high infant mortality rate. The Guilford County Adopt-A-Mom
      Program.

PMID- 9558901
TI  - Isolated extremity soft tissue injury. An occupational hazard in rural eastern
      North Carolina.

PMID- 9558902
TI  - Emergency events involving hazardous substances in North Carolina, 1993-1994.

PMID- 9558903
TI  - Shortening hospitalization after appendectomy in children.

PMID- 9558904
TI  - Management of lower extremity venous stasis ulcers in a comprehensive wound care
      clinic.

PMID- 9558905
TI  - [Quality of life in medicine].

PMID- 9558906
TI  - [DRG's and cost/efficacy indicators in nephrology and dialysis. Results at a
      hospital division].
AB  - The Diagnosis Related Groups (DRGs) classification system correlates hospital
      performance with their relative costs and encourages more efficient productive
      processes. We report the following parameters: a) the distribution of hospital
      discharges according to the Major Diagnostic Categories (MDCs) and DRGs; b) the
      relationship between mean length of stay and threshold values; c) economic
      analysis of the cost-reimbursement pay-off. The results showed that 71.3% of DRGs
      belonged to nephro-urological MDC 11 and 28.7% in other internal MDCs (mainly
      involving cardiac and respiratory system). Of the latter, 67.7% were utilized for
      dialysis and transplant patients and kidney donors. In MDC 11 the most common
      DRGs were: the surgical DRG 315, produced by the vascular accesses for
      hemodialysis and by insertion of Tenckoff catheter for peritoneal dialysis, DRG
      316 by cases of acute and chronic renal failure, DRG 332 by biopsy-proven
      glomerulonephritides. The length of stay was most commonly within range of one
      third of threshold value for specific DRG; there was a low percentage of one-day
      stays and outlier cases. The economic analysis demonstrated that mean daily
      reimbursement sum was 590,714 ITL. Analysis of the overall costs yielded a mean
      daily cost of 455,838 ITL. In conclusion, quality indicators show that,
      appropriately, our specialist activity is largely devoted to the diagnosis and
      treatment of acute and chronic nephropathies and complications following dialysis
      and renal transplant.

PMID- 9558907
TI  - [High prevalence of hepatitis C virus infection in patients with non-Hodgkin's
      lymphoma at the onset. Preliminary results of an Italian multicenter study].
AB  - 143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this
      perspective study on NHL-associated risk factors. They were 87 males and 56
      females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis
      C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5
      17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated
      (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low
      grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was
      B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection
      was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset
      in the other 10 patients. In these 10 patients the median time between HCV
      infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data
      confirm that in Italy the prevalence of HCV infection in patients with NHL
      (11.2%) is significantly higher than expected in the general population (1.3
      3.2%). The finding that, in most cases, HCV infection was definitely antecedent
      to NHL onset, usually by years, adds evidence to the possible causative role of
      the HCV in lymphomagenesis.

PMID- 9558909
TI  - [Chronic lymphatic leukemia and large granular lymphocytes].
AB  - Chronic large granular lymphocyte leukemia is a rather rare disorder (less than
      5% of LLC). Its subtype CD3+/CD8+ is often a clonal disease and without malignant
      characteristics. This kind of disease shows a clinical and laboratory
      heterogeneity, probably due to the immunological and functional variety of
      granular lymphocytes. In some cases of LGL leukemia an associated pathology,
      especially rheumatoid arthritis and chronic infections, has been reported. On the
      contrary, the relationship with neoplasms has been rarely proved in literature:
      only occasional studies have been reported and anyway they are not supported by a
      sufficient number of cases. Two cases of LGL leukemia are here delineated: a
      woman with advanced breast adenocarcinoma and another one with Sjogren disease.
      The first one had a rapidly fatal course, while the other one had a prolonged
      clinical course with chronic neutropenia (13 years follow-up). The association
      between carcinoma and LGL leukemia may be just a casual finding but the
      hypothesis of a possible relationship is however very interesting on account of
      the important role of granular lymphocytes in controlling tumoral growth.
      Moreover, both patients had concomitant chronic HCV-correlated infection: maybe
      it will worth making a prevalence study with a greater number of cases, in order
      to evaluate a probable relationship between these pathologies. The growth factor
      G-CSF may be useful in the treatment of infections that often occur in patients
      with severe neutropenia.

PMID- 9558908
TI  - Five day intermittent vs seven day continuous 2-chlorodeoxyadenosine infusion for
      the treatment of hairy cell leukemia. A study by Italian Group for the Hairy Cell
      Leukemia.
AB  - The new purine-analogue 2-chlorodeoxyadenosine (2-CdA) has proved to induce an
      high CR rate and a long lasting disease free survival. In this study we compare
      the efficacy and toxicity of 2-CdA employed in two different schedules (A and B).
      Forty-one patients have been enrolled from 1994: 22 p. (group A) were treated
      with a single cycle of 2-CdA given as two hour i.v. infusion on 5 consecutive
      days (0.15 mg/kg/die); while 19 p. (group B) with continuous i.v. infusion for 7
      consecutive days (0.10 mg/kg/die). Response criteria were those proposed by NCI.
      The Hairy Cell Index (HCI) was calculated using DBA44 MoAb. At three months, the
      responses in group A (19/22) were: 5 CR (26.3%), 6 GPR (31.5%), 5 PR and 3 NR.;
      in group B (17/19): 6 CR (35.3%), 3 GPR (17.6%), 4 PR and 4 NR. Overall response
      at six months was respectively 84.2% and 76.5%. At six months the responses were:
      in group A (18/22): 9 CR (50%), 4 GPR (22.2%), 3 PR, 2 NR; in group B (16/19): 4
      CR (25%), 6 GPR (37.5%), 3 PR, 3 NR. Overall response at 6 months was
      respectively 88.8% (group A) and 81.2% (group B). The 5 day intermittent schedule
      appears efficient, well tolerated and suitable for out-patient treatment. DBA44
      MoAb appears useful to better define the HCI and to distinguish CR from GPR.

PMID- 9558910
TI  - [MALT lymphoma of the left lacrimal and mammary glands, liver cirrhosis caused by
      HCV and type II cryoglobulinemia].
AB  - We describe a case of MALT (mucosa-associated lymphoid tissue) lymphoma
      associated to post-hepatitis C liver cirrhosis, type II cryoglobulinaemia,
      gastrointestinal bleedings and thromboses. HCV infection justified the
      association between the first three pathologies, while gastrointestinal bleedings
      and thromboses were respectively attributed to portal hypertension secondary to
      liver cirrhosis and to some thrombophilic conditions. Among the latter there was
      also an antithrombin III deficiency. The singularity of the case and some
      difficulties met in its treatment, justify the report.

PMID- 9558911
TI  - [Clinical spectrum of extrapulmonary sarcoidosis. From the onset to organ
      transplantation].

PMID- 9558912
TI  - [Role of autologous stem cell transplantation in the treatment of Hodgkin's
      lymphoma].
AB  - Among lymphomas, treatment of Hodgkin's disease (HD) allows the highest cure
      rate. Radiotherapy (RT) represents first choice therapy in early stages,
      providing complete remission (CR) rate even superior to 90%. Chemotherapy (CHT)
      or, when indicated, the combined modality treatment (CHT + RT) is successful, in
      terms of long overall survival (> 10 yrs) in more than 60% of patients with
      advanced stage disease at onset. Considering all stages of disease at onset,
      about 75% of patients can be cured. However, the remaining 25% results resistant
      to the conventional approach (CHT +/- RT) or, mainly, relapses after first CR.
      For these poor prognosis patients, it has been assessed the possibility of
      inducing (or reinducing) a CR by using high dose CHT with stem cells rescue.
      Autologous stem cell transplantation (ASCT) consists in the administration of
      antiblastic drugs at so high dosages to require the consequent reinfusion of stem
      cells, preventively harvested and cryopreserved, thus dramatically decreasing the
      risk of a prolonged bone marrow aplasia. This procedure is currently performed as
      intensification treatment in selected cases of patients with advanced stage at
      onset, once in CR after first-line therapy. Therefore, the development of
      prognostic models aimed to define with higher sensibility and specificity
      patients at high risk of relapse and to be submitted to ASCT as consolidation
      therapy, is becoming of increasing interest.

PMID- 9558913
TI  - Mechanosensitive ion channels in nonspecialized cells.

PMID- 9558915
TI  - [Treatment of hypothyroidism].

PMID- 9558914
TI  - Calcium and neuronal death.

PMID- 9558916
TI  - [The importance of HIV in the Spanish woman].

PMID- 9558917
TI  - [Results of treatment of Graves-Basedow disease with 131I at low calculated
      doses].
AB  - OBJECTIVE: To evaluate the results of treatment of Graves' disease with 131I at
      low calculated doses. METHODS: A total of 333 patients with Graves' disease were
      treated with low calculated doses of 131I on the basis of thyroid size and 131I
      uptake (mean doses = 6.6 +/- 1.9 mCi). The mean follow-up was 24.4 months (range
      12-145). RESULTS: The accumulated likelihood of hypothyroidism at 145 months of
      follow-up was 89.8% (Kaplan-Meier method) and relapse 26%. Pretreatment levels of
      T3 above 9 nmol/l were associated with a lower incidence of hypothyroidism (p =
      0.049, Mantel-Cox method). Pretreatment levels of T4 above 300 nmol/l were
      associated with a higher risk of therapy failure (odds ratio 3.27; 95% confidence
      interval = 1.3-8.2, Cox method). Age, sex, previous therapy with anti-thyroid
      agents or surgery, 131I uptake, initial and total dose of 131I, number of
      administered doses and development of transient hypothyroidism were not
      predictive of the evolution of thyroid function. CONCLUSION: Therapy of
      hyperthyroidism (Graves' disease) with low calculated doses of 131I shows a high
      incidence of hypothyroidism, also increasing the cost involved in estimating the
      dose and long-term follow-up.

PMID- 9558918
TI  - [Prevalence of psychiatric disturbances and psychopathologic status in patients
      with systemic lupus erythematosus].
AB  - BACKGROUND: Psychiatric disorders are commonly associated with systemic lupus
      erythematosus (SLE). Some authors consider that these disorders can be associated
      with cognitive impairment. OBJECTIVES: The objectives of this study were to
      establish the particular prevalence of psychiatric disorders in these patients
      and to investigate the relationship between psychiatric disorders, cognitive
      impairment, life quality, psychological status and adjustment to illness.
      MATERIAL AND METHODS: A cross-sectional study is reported of 46 spanish patients
      with systemic lupus erythematosus (SLE) attending the outpatients clinics of the
      Internal Medicine and Rheumatology Departments at a University Hospital. The
      following instruments were used: a Structured Clinical Interview for DSM-III-R,
      the Nottingham Health Profile, the Symptom Check-List 90-Revised, the
      Psychological Adjustment to Illness Scale and the Integrated Program of
      Neuropsychological Assessment Test-Barcelona. RESULTS: The prevalence of
      psychiatric disorders at interview was 33%. The most common diagnoses were
      affective disorders and psycho-organic syndrome. Affective disorders were
      associated with a poorer life quality, number of hospitalizations and psychiatric
      background. Adjustment to illness accounted for the psychologic status of the
      patients.

PMID- 9558919
TI  - [Epidemiology of Paget's disease. Peculiarities in the province of Zamora].
AB  - BACKGROUND: Some paramyxovirus (measles, respiratory syncytial virus, and dog's
      distemper virus) are currently considered to be responsible for Paget's disease
      of the bone. A relevant role is also given to inheritance as predisposing factor.
      Some authors have found an association between HLA antigens with this disease,
      but without unanimous agreement. Although this hypothesis of an interaction
      between a genetic factor and a viral infectious agent is the most accepted
      universally, there is not yet a definitive cause for the disease. The
      participation of some other environmental factors has not been ruled out.
      METHODS: One hundred and forty patients in the Zamora province were studied. The
      geographic distribution in the different areas of the province was analyzed and
      also whether there was family aggregation all cases. HLA-I was determined in 59
      patients and HLA-II in cases with aggregation. The mineral composition (calcium,
      fluorine, magnesium, nitrates, and chlorine) analysis of public running water was
      carried out in all population centers in the province. RESULTS: Aggregation was
      found in four families (four, two, four, and three siblings, respectively).
      Although HLA-I antigens were determined in 59 patients, no association was found.
      HLA-II antigens were also determined in the involved patients with family links
      and no association was found between these antigens and the disease. A much
      higher aggregation was found in some particular areas in our province and these
      foci coincided with some characteristics of mineral composition of public running
      waters. CONCLUSIONS: There is a genetic factor predisposing to the disease, as
      family aggregation occurs with a higher frequency than would otherwise be
      expected. Nevertheless, no association with HLA antigens was found. This disease
      is more common in some particular geographic areas, thus supporting the
      hypothesis of an environmental factor as trigger. An association was found
      between mineral composition of public running waters and patient geographic
      distribution.

PMID- 9558920
TI  - [Primary adrenal failure and AIDS: report of 11 cases and review of the
      literature].
AB  - OBJECTIVE: To know the prevalence of adrenal insufficiency (AI) in our patients
      with acquired immunodeficiency syndrome (AIDS) and to compare the clinical
      manifestations with those reported in previous series in the literature. PATIENTS
      AND METHODS: Retrospective study with review of clinical records of patients with
      AIDS diagnosed of AI (plasma cortisol after synthetic ACTH < 18 micrograms/dl) in
      our hospital for a period of 6 and a half years. RESULTS: Eleven out of 65
      patients (17%) with the hormonal study performed were diagnosed of AI. The
      prevalence of AI in our patients with AIDS was 1.66%. The response of plasma
      cortisol to synthetic ACTH was abnormal in the 11 patients (mean increase: 1.89
      micrograms/dl). Nine out of the 11 patients had a decreased basal plasma cortisol
      level (mean: 4.75 micrograms/dl). Basal plasma ACTH levels were increased (mean:
      638.9 pg/ml) in seven out of nine patients. Patients were severely
      immunosuppressed (mean CD4: 21/microliter). While the clinical course was
      subacute (mean: 5.1 weeks), nine out of the eleven patients developed an adrenal
      crisis which required emergency therapy. Ten patients had an opportunist
      infection--M. tuberculosis (3), M. avium-intracellulare (3), Cytomegalovirus (3),
      histoplasmosis (1)--which could involve the adrenal glands in ten patients. All
      patients responded to treatment but their mean survival was 5.6 weeks.
      CONCLUSIONS: Although the prevalence of AI in our patients with AIDS was low
      (1.66%), it is important to be aware of the disease and to order a basal plasma
      cortisol value after synthetic ACTH, as treatment improves the life quality of
      patients if AI is confirmed, despite a short survival time.

PMID- 9558921
TI  - [Casual fall, pain, and abdominal distension].

PMID- 9558922
TI  - [Skin rash and pulmonary nodule].

PMID- 9558923
TI  - [William's syndrome. Report of a case with family involvement].
AB  - Williams' syndrome (WS) is a rare genetic condition of autosomal dominant
      inheritance with varying penetrance, which consists of supravalvular aortic
      stenosis, a characteristic dysmorphic facies named "elf face", mental retardation
      and other clinical manifestations including transient infantile idiopathic
      hypercalcemia, growth retardation, and frequent dental problems. It usually
      presents sporadically, and there are only a few cases of family involvement
      reported in the literature. Recent studies show that mutations in the elastin
      gene at chromosome 7q11.23, which occur approximately in 90% of cases, could be
      the cause of the different clinical manifestations in this syndrome. In this
      paper we report a case of family involvement with five family members involved
      with WS (three siblings, the mother, and the siblings' maternal uncle) and all
      had cardiac structural disorders (supravalvular aortic stenosis being the most
      frequent), a characteristic face and a low intellectual coefficient. The
      complementary tests included blood chemistry, chest X-ray, and echocardiogram,
      which led to the diagnosis of the associated valve pathology. Three patients
      required therapeutic catheterism with Stent valve implant and valve prosthetic
      replacement to control cardiac manifestations.

PMID- 9558924
TI  - [Classical Kaposi sarcoma of aggressive course].
AB  - The aggressive variant of the classical Kaposi sarcoma (KS), though uncommon, has
      an utmost relevance because its evolutive characteristics entail a great
      morbidity and mortality. Three classical KS cases are reported which manifested
      an unusually aggressive course, with extensive cutaneous and visceral
      involvement. One of the patients was diagnosed of a non-Hodgkin lymphoma 12
      months later. None of the three patients responded to the different therapeutic
      regimens used: polychemotherapy, monochemotherapy and interferon-alfa,
      respectively. The three patients died within two years after diagnosis. In KS
      patients with pulmonary involvement, working in coal mines was recorded as
      occupational antecedent. These three cases illustrate the different clinical and
      therapeutic characteristics of an uncommon subtype in the KS spectrum in general
      and of its classical variant in particular. Likewise, the possible role of
      occupational exposure in the etiopathogenesis of KS is discussed.

PMID- 9558925
TI  - [Factors modifying alcoholemia].

PMID- 9558926
TI  - [New antiviral agents in chronic viral hepatitis].

PMID- 9558927
TI  - [Perforation of vena cava inferior as a late complication of an Antheor type
      filter].

PMID- 9558928
TI  - [Subacute lupus erythematosus and psoriasis].

PMID- 9558929
TI  - [Inaccuracy of bibliographic references: are non-read articles cited?].

PMID- 9558930
TI  - [Prevalence of hepatitis C virus infection in patients with lichen planus in
      Badajoz province].

PMID- 9558931
TI  - [Os odontoideum: an entity to be considered in every acute bulbospinal
      involvement].

PMID- 9558932
TI  - [Personality and anesthesiology. An area to explore].

PMID- 9558933
TI  - [Anatomical description of a natural perforation present in the human lumbar pia
      mater].
AB  - OBJECTIVE: The pia mater has always been considered more permeable than other
      meningeal membranes. Natural pia mater perforations found in some animals at-test
      to this membrane's permeability. Such perforations, however, have never been
      demonstrated in human tissue. Our objective was to study human pia mater from the
      dorsal lumbar region, looking for perforations that facilitate the diffusion of
      substances to the spinal cord following subarachnoid administration. MATERIAL AND
      METHOD: The specimens were removed from four human cadavers aged 70, 72, 77 and
      78 years between 8 and 12 hours after death. The specimens were fixed in a
      phosphate glutaraldehyde buffer solution, followed by desiccation in acetone and
      critical point elimination of acetone, treatment with carbon and metallization
      with gold. RESULTS: The pia mater was composed of a smooth surfaced, thin layer
      of cells and underlying connective tissue formed mainly of collagen fibers and
      fundamental amorphous matter. The collagen fibers were oriented in various
      directions. Throughout the surface of the pia mater, natural circular, elliptical
      and ovoid perforations were distributed irregularly. Size varied. Most measured
      over 10 to 15 micrometers in diameter or less than 5 to 8 micrometers. Inside the
      openings, fibers similar to collagen fibers could be seen at the point where they
      would normally be found beneath the cell layer. CONCLUSION: The total thickness
      of the pia mater varies in different zones of the spine, as a result of
      variations in the thickness of the cell layer and in the underlying extracellular
      layer. The existence of natural fenestrations in all the analyzed specimens of
      human dorsal lumbar pia mater accounts for the high permeability of this
      membrane, which permits substances administered in spinal fluid to reach the
      spinal cord. These natural fenestrations are areas where the cell surface in
      absent, with underlying collagen fibers usually visible. The pia mater is
      generally believed to be composed of a complete cell layer that forms a barrier
      between the central nervous system and the subarachnoid space; however, the
      presence of fenestrations would indicate that such a barrier does not exist, the
      base membrane being placed under the connective fibers, the only intact structure
      prior to medullary glial cells.

PMID- 9558934
TI  - [Is crystalloid cardioplegia still a valid technique for myocardial myocardial
      protection?].
AB  - OBJECTIVES: The routine use of a cardioplegic solution for myocardial protection
      during the ischemic phase of cardiac surgery represents a great therapeutic
      advance. Two cardioplegic solutions are currently in use: crystalloid and blood
      solutions. As blood cardioplegia has been shown to offer superior myocardial
      protection, its use at present is widespread. We did a retrospective study to
      assess whether crystalloid cardioplegia might nevertheless continue to be useful.
      PATIENTS AND METHODS: Forty patients with heart disease underwent surgery between
      March 1994 and March 1995, with the use of crystalloid cardioplegia (group A).
      Blood cardioplegia was used in 72 patients during the same period (group B).
      RESULTS: There were no significant differences in clinical (age, arterial
      hypertension, diabetes, chronic bronchial disease, severity of angina, severity
      of heart disease) or surgical (emergency, percent use of the internal thoracic
      artery, duration of extracorporeal circulation) variables. The percentage of
      patients with low ejection fraction was higher in group B as a result of
      preoperative selection. The mean number of grafts was higher in group B than in
      group A (3.5% and 2.5, respectively) (p < 0.01). Postoperative results (use of
      inotropics, counterpulsation balloon, creatine phosphokinase, perioperative
      myocardial infarction or hospital mortality) were not significantly different.
      The percent of supraventricular arrhythmias after surgery was higher in group A
      than in group B (20% and 5%, respectively) (p < 0.05) and lactic dehydrogenase
      level was lower in group A than in group B (472 and 572 mu/l, respectively) (p <
      0.05). CONCLUSIONS: We believe that crystalloid cardioplegia continues to be a
      valid and effective myocardial protection technique in heart patients with
      preserved left ventricular systolic function.

PMID- 9558935
TI  - [Changes in therapeutic attitude based on transesophageal echocardiography in
      cardiac surgery].
AB  - Transesophageal echocardiography is a monitoring system that is changing the
      practice of cardiovascular anesthesia and surgery by providing real time images
      of cardiovascular anatomy and pathophysiology. Our hospital's anesthesiology and
      postoperative intensive care departments, in particular the cardiac anesthesia
      team, initiated a joint project in June 1993 with the echocardiography laboratory
      team to incorporate this surgical monitoring system. Here we report the wealth of
      information we obtained and describe the possibility of modifying a therapeutic
      approach based on the images visualized, even when conventional monitoring gives
      contradictory information. Two illustrative case reports are included.

PMID- 9558936
TI  - [Asystole after intravenous administration of ranitidine].

PMID- 9558937
TI  - [Voluntary intoxication with isoniazid].

PMID- 9558938
TI  - [Accidental intra-arterial diazepam injection].

PMID- 9558939
TI  - [Spanish anesthesiologist in European scientific forums: The European Society of
      Anesthesiologists and The European Society of Regional Anesthesia].

PMID- 9558940
TI  - [Tracheal rupture after endotracheal intubation: clinical developments in two
      cases].

PMID- 9558941
TI  - [Acute myocardial infarction during catheterization of the left subclavian vein].

PMID- 9558942
TI  - [Age limit for liver transplantation].

PMID- 9558943
TI  - Thyroid function in acute pancreatitis.
AB  - OBJECTIVES: To analyze changes in the thyroid function in patients with acute
      pancreatitis. METHODS: Admission serum levels of triiodothyronine (T3), reverse
      triiodothyronine (rT3), thyroxine (T4) and thyrotropin (TSH) were determined in
      20 patients with pancreatitis and 20 healthy control patients. Another group of
      20 patients with upper digestive haemorrhage was included to study possible
      changes in the pattern of thyroid function in hemodynamic alterations. In
      addition, laboratory indicators of liver, renal and pancreatic functions were
      measured in all groups. RESULTS: Our results demonstrated low levels of T3 in 20%
      of patients with pancreatitis and increased rT3 levels in 75% of them.
      Thyrotropin was always among reference ranges and only one case presented a low
      level of T4. No significant alterations were detected in patients with upper
      digestive haemorrhage. CONCLUSIONS: These results suggest that pancreatitis may
      play a role in the genesis of these changes, since other factors such as diet and
      cellular hepatic alteration appear to have had no effect on the levels of thyroid
      hormones in these patients. In other studies those changes in the thyroid
      function can be relationed with the prognosis in acute pancreatitis.

PMID- 9558944
TI  - Endoscopic pancreatic stent drainage improves pain in chronic pancreatitis.
AB  - Pain in chronic pancreatitis is due to intraglandular neural affection and to
      pancreatic duct drainage obstruction with an increased intraductal pressure. To
      achieve pain relief, medical, surgical and endoscopic procedures have been
      developed. AIM: To evaluate the efficacy of pancreatic duct stenting in patients
      with narcotic-dependent pain due to chronic pancreatitis. PATIENTS AND METHOD:
      From May-1994 to May-1996, ten patients (medium age: 47.5 yr) with alcoholic
      chronic pancreatitis were selected for this procedure. Pancreatography showed
      single or multiple Wirsung strictures in all cases. Papillotomy and pancreatic
      duct sphincterotomy were performed before stenting. Strictures were negotiated
      with a 7F dilating catheter over a guide wire, and intraductal calculi were
      removed as well. We used 7F plastic stents with variable lengths (5-10 cm), that
      were exchanged when the patient presented pain recurrence. Stent survival time
      was defined as the patient's pain-free time. RESULTS: In 6 of the 10 patients
      stent placement was carried out successfully. A single distal Wirsung stricture
      was diagnosed in 3 patients while in the remaining 3 there were several
      strictures associated to ductal lithiasis in two of them. Mean time to achieve
      pain relief was 3 days and mean stent survival time was 166.5 days. There were no
      complications due to the procedure. CONCLUSIONS: When placed through the
      stricture, endoscopic pancreatic stent drainage is effective in achieving pain
      relief. It is a safe procedure with no complications in our short series.

PMID- 9558945
TI  - Acute biliary pancreatitis: sphincter of Oddi and choledochal pressure.
AB  - Twenty four patients with biliary pancreatitis were divided into three groups: A
      (18 subjects underwent surgery on the biliary tract seven days after admission to
      hospital when acute signs disappeared); B (3 cases were operated two months
      later), and C (3 patients underwent emergency surgery for acute cholescistitis
      with simultaneous acute pancreatitis). A cholecistectomy-choledochostomy through
      a Kehr tube was performed in all patients. Pressure in the main biliary duct
      (MBD) was measured. Only group A was significant (18 cases). As a control,
      another group, group D was considered (52 biliary cholecysto-choledochal
      lithiasis patients without pancreatitis and without transduodenal
      sphincterotomy). Group A: 1) The mean pressure in MBD on the fourth postoperative
      day (11 days after onset of pancreatitis) was low (p < 0.0001) in relation to
      that of group D with Oddi's sphincter (SO) normal; 2) in group A, no significant
      differences (p-NS) were found in relation to positions: during fasting, 4.4 +/- 4
      cm H2O in the upright position, and 5.3 +/- 2 when lying (in group D, 9.9 +/- 4.1
      cm H2O upright, and 7.76 +/- 3.6 lying with p = 0.0001), and 3) a slow
      improvement of pressure was observed and, on the 25th day after operation, it was
      nearly normal (9 cm H2O upright and 7 cm lying with p < 0.001). Group B: biliary
      surgery at 2 months; mean pressure in MBD meartly normal. Group C: 1) 4 days
      after emergency surgery, the pressure in MBF (15 cm H2O upright and 11.7 lying)
      was higher than in subjects with normal SO, probably due to compression of the
      distal part of MBD by the inflamed pancreas, and 2) from the 11th day the
      pressure followed the same evolution as that of group A. In conclusion, in
      patients with acute biliary pancreatitis, operated on the biliary tract when
      acute signs disappeared, MBD pressure is low (p < 0.0001) in reference to normal
      on the fourth post-operatory day (11 days after onset of pancreatitis) and no
      significant differences were found in relation to positions (upright and lying).
      The pressure changes are transient (4-5 weeks) and most probably due to the
      lesions and malfunction of the SO related to pancreatitis.

PMID- 9558946
TI  - [Hepatocellular carcinoma associated to porphyria cutanea tarda and hepatitis C
      virus infection without cirrhosis].
AB  - The molecular basis of porphyria cutanea tarda is defective activity of hepatic
      uroporphyrinogen decarboxylase. A common characteristic is liver dysfunction than
      goes from cirrhosis to hepatocellular carcinoma. A high prevalence of hepatitis C
      virus markers has been demonstrated. We study a patient with PCT and hepatitis C
      virus markers that finally develops to hepatocellular carcinoma without previous
      cirrhosis. Previous studies with association of PCT and hepatitis C virus
      markers, have found liver diseases ranging from cirrhosis to hepatocellular
      carcinoma. The importance of this study is the absence of cirrhosis.

PMID- 9558947
TI  - [Surgical treatment of hepatolithiasis. Presentation of a case].

PMID- 9558948
TI  - [Massive lower intestinal hemorrhage in Wegener's disease].

PMID- 9558949
TI  - [Blocking of T-type calcium channels: new horizons in the therapeutic potential
      of calcium antagonists].

PMID- 9558950
TI  - [Nocturnal arterial hypertension and cardiovascular risk].

PMID- 9558951
TI  - [Left ventricular filling in young patients with systemic lupus erythematosus in
      stable phase].
AB  - OBJECTIVE: The aim of this study was to evaluate the left ventricle filling
      pattern in patients with stable systemic lupus erythematosus (SLE). METHODS: This
      prospective study was performed in 22 healthy controls and in 24 patients with
      stable SLE. These two groups were submitted to a clinical, electrocardiographic
      and echocardiographic evaluation. RESULTS: Gender distribution and mean age were
      similar in both groups (p = NS). Patients with SLE were more symptomatic (21%)
      than control patients (0%) (p < 0.01). Left ventricular dimensions, wall
      thickness, and systolic function were not significantly different between the two
      groups. However, pericardial effusion was more frequently found in patients with
      SLE (21%) when compared to the control group (0%) (p < 0.05). When compared to
      the control group, patients with SLE showed an abnormal left ventricular filling
      pattern. Peak late mitral flow velocity was 0.45 +/- 0.2 m/sec in SLE patients
      and 0.36 +/- 0.1 m/sec in the control group (p = 0.001). CONCLUSION: These
      results demonstrate that patients with stable SLE, when compared to healthy
      controls, are frequently associated with cardiovascular symptoms, asymptomatic
      pericardial effusion, and an abnormal left ventricular filling pattern.

PMID- 9558952
TI  - [Partial pericardectomy using videothoracoscopy].
AB  - OBJECTIVE: The aim of this study is to assess the validity of videothoracoscopy
      in the treatment of chronic pericardial effusions. STUDY PATIENTS: We studied 13
      consecutive patients with chronic pericardial effusions and an indication for
      surgical treatment. The patients, 10 female and 3 male, had a mean age of 48
      years (21-72 years). Eleven patients had recurrent pericardial effusion and two
      patients had anterior mediastinal masses of unknown etiology and a large
      pericardial effusion. METHODS: A videothoracoscopy was performed in every
      patient, under general anesthesia with a double-lumen endotracheal tube. The
      thoracic cavity was inspected, the pericardial effusion was drained and a partial
      pericardectomy was performed. RESULTS: There was no postoperative mortality or
      morbidity. Average duration of postoperative thoracic drain and postoperative
      stay were, 1.2 and 2.4 days respectively. Follow-up ranged from 1 to 48 months
      (mean 23.3 months). One patient died due to progression of his malignant disease.
      There were no cases of recurrent pericardial effusions. CONCLUSIONS: Video
      assisted pericardectomy is a safe technique that should be considered in the
      treatment of chronic pericardial effusions.

PMID- 9558953
TI  - [New parameter for explaining the "natural protection" of the female sex in
      cardiovascular risk (the value of arterial baroreceptors)].

PMID- 9558954
TI  - [Association of nutritional status, body composition, serum lipids and
      apolipoproteins, and haptoglobin phenotype in a population of 9- to 12-year
      olds].

PMID- 9558955
TI  - [Coronary disease in patients undergoing heart transplantation: are there
      predisposing factors?].

PMID- 9558956
TI  - [Evaluation of myocardial viability using overload echocardiography in coronary
      disease with severe left ventricular dysfunction: influence on the therapeutic
      decision and results of revascularization].

PMID- 9558957
TI  - [Diagnosis of coronary disease in patients having undergone a heart transplant:
      does myocardial perfusion tomoscintigraphy allow to exclude heart
      catheterization?].

PMID- 9558959
TI  - [Variation in the calculation of the left ventricular mass using three
      dimensional echocardiography].

PMID- 9558958
TI  - [Elevation of the ST segment in derivations with Q wave in early exertion test
      after acute myocardial infarct: a marker for ischemia/viability].

PMID- 9558960
TI  - [Value of echocardiography and heart Doppler in the diagnosis and therapeutic
      orientation of congestive heart failure--the importance of diastolic
      dysfunction].
AB  - Echocardiography and cardiac-Doppler are very useful techniques to achieve
      etiologic diagnosis and evaluate therapeutic strategies for heart failure, and
      left ventricular hypertrophy is known as a serious risk factor for cardiovascular
      disease morbidity and mortality. Echocardiography establishes, in an easy and
      noninvasive way, the etiologic diagnosis of heart failure and is a very sensitive
      technique for the diagnosis and follow-up of patients with left ventricular
      hypertrophy. On the other hand, diastolic dysfunction is an early manifestation
      of several conditions associated with heart failure emerging from the diastolic
      mechanism. The author emphasizes the role of cardiac Doppler in the early
      diagnosis of diastolic dysfunction and how findings provided by this procedure
      can lead to more adequate therapeutic measures and assess accurate prognostic
      information.

PMID- 9558961
TI  - Optimizing timing of surgical correction in patients with severe aortic
      regurgitation: the role of symptoms.

PMID- 9558962
TI  - Laser and serum opsonic activity.
AB  - The purpose of this study was to investigate the effects of low level laser (LLL:
      GaA1As diode laser; 830 nm) on serum opsonic activity, which was assessed by
      neutrophil-associated chemiluminescence (CL) response to zymosan opsonized with
      sera irradiated in vitro with various doses of LLL. We used both lucigenin
      dependent CL (LgCL) for superoxide (O2-) detection and luminol-dependent CL
      (LmCL) which detects myeloperoxidase (MPO)-dependent formation of hypochlorous
      acid in combination with MPO inhibitor, sodium azide (NaN3). When serum opsonic
      activity was assessed by LgCl, NaN3, markedly enhanced the responses, suggesting
      that O2- is accumulated due to the MPO blockade, leading to the excitation of
      LgCl. However, LLL-irradiation had no effects on serum opsonic activity. On the
      other hand, when serum opsonic activity was assessed by LmCl, NaN3, strongly
      inhibited the response. The effects of LLL at different output powers were
      characterized by similar values, but significantly higher values were observed at
      the highest dose tested (60 mW for 1 min) in the absence of NaN3. Since this
      enhancement effect disappeared with NaN3, it was suggested that high dose LLL
      irradiation probably activated the opsonic activity by facilitating neutrophils
      to degranulate MPO. However, lower doses used for therapeutic purposes had no
      effects at any output powers tested.

PMID- 9558963
TI  - Inhibitory capacity of some fractions isolated from a green barley extract upon
      TNF alpha production by the cells of the THP-1 human monocytes line.
AB  - A green barley extract commercialized as an antiinflammatory product under the
      name of "Natural SOD" was fractionated based on the molecular weights principle.
      Knowing that the TNF alpha cytokine plays an important role in inducing
      inflammatory phenomena, by the use of two determination methods (ELISA and
      cytotoxicity), the fractions obtained were analysed for their capacity to
      modulate TNF alpha production/release by an LPS-activated human monocytes line
      (THP-1). The results pointed to the existence of 3 groups of substances
      (fractions 3, 4 and 9) apt to modulate TNF alpha production, fraction 4 being the
      most active. Of the TNF alpha determination methods, ELISA proved to be more
      sensitive as it detected not only free TNF alpha identified also by the
      cytotoxicity test, but also TNF alpha complexed with its soluble receptors. The
      presence of these substances in Natural SOD, fractions with modulatory action
      upon TNF alpha production, might partly account for the clinical efficiency of
      this product in the treatment of inflammatory affections reported in humans.

PMID- 9558964
TI  - Antidiphtheria and antitetanus immunity of recruits in Romania.
AB  - The concern for maintaining a high antidiphtheria and antitetanus immunity level
      is permanent. The paper approaches the study of antidiphtheria and antitetanus
      immunity levels in a group of young recruits (who had been administered a DT
      booster 5-7 yrs before). The titres of antibodies were determined concomitantly
      by the neutralization test (NT) in vivo and by the passive hemagglutination assay
      (PHA) in vitro. The results obtained by the neutralization tests revealed (by the
      estimations shown by the geometrical means) a high antidiphtheria and antitetanus
      immunity level proved by an exceeding of the protection limits (0.03 IU/ml and
      0.01 IU/ml) of 89 x and 953 x, respectively. The analysis of individual titres
      obtained by NT showed that of 540 subjects in whom diphtheria antitoxin was
      determined, 93.52% had protective titres, while of 619 subjects in whom the
      tetanus antitoxin was evaluated, 97.26% were immune. The results obtained by PHA
      were comparable with those obtained using the reference methods.

PMID- 9558965
TI  - Plasmid profile analysis and restriction enzyme analysis in characterizing
      Shigella flexneri isolates from an outbreak.
AB  - Shigella flexneri strains which are multiply resistant to antimicrobial agents
      were isolated from 11 children from an orphanage in Cluj-Napoca during an
      epidemiological investigation initiated by the Department of Epidemiology.
      Plasmid profile analysis and restriction endonuclease analysis were used in
      conjunction with biotyping, serotyping and antimicrobial susceptibility testing
      for identifying epidemiological related isolates. All strains were serotype 2a
      and with one exception all of them showed the same resistotype. Plasmid profile
      analysis differentiated S. flexneri isolate into four patterns, with two common
      plasmids of 3.5 and 1.9 kb. This study indicates that this outbreak was caused by
      at least two different strains of S. flexneri which were not differentiated by
      the classical technique-biotyping, serotyping and antimicrobial susceptibility
      pattern.

PMID- 9558966
TI  - Incidence of Chlamydia trachomatis genital infections in Bucharest (1988-1996).
AB  - 2230 patients from Bucharest with genital infections were investigated (1988
      1996) to identify the chlamydial etiology. The rate of isolation of Chlamydia
      trachomatis was of 33.8%. The highest percentages were reported in patients
      clinically diagnosed with cervicitis (56.2%) and non-gonococcal urethritis (36%);
      as well as in patients aged 31-35 years, single, who had genital urinary
      infections in history.

PMID- 9558967
TI  - Rapid test for the detection of methicillin-resistance of staphylococci by ATP
      dependent bioluminescence.
AB  - Methicillin resistance of staphylococci is a marker of multiple resistance to
      antimicrobial drugs. The authors present their own variant of applying ATP
      dependent bioluminescence for the rapid testing of methicillin resistance. It
      consists in the measurements of the total bacterial ATP obtained by extraction.
      The authors test the method on 23 Staphylococcus strains and compare the results
      with those obtained by the diffusion method, the screening method with the
      antibiotic included in the agar and the broth dilutions method. The results
      obtained by ATP-dependent bioluminescence were in agreement with those obtained
      by broth dilutions method.

PMID- 9558968
TI  - Viral etiology of acute respiratory infections in infants and young children.
AB  - 114 children with acute respiratory infections were investigated to detect the
      viral etiological agents. The following methods were used: the direct
      immunofluorescence technique for the rapid diagnosis from tracheobronchial
      aspirates and the serological reactions--hemaglutinoinhibition and complement
      fixation reaction--to determine the increase of antibodies titres. Of 55.2%
      respiratory infections with a viral etiology, 60.3% represent acute infections of
      the lower respiratory tract. Due to the influenza epidemic reported between
      October 1996 and February 1997 (with a higher number of cases than in the last 5
      years), most viral respiratory infections were caused by influenza viruses
      (57.14%). The direct immunofluorescence technique proved to be sensitive and
      specific in detecting the viral etiological agents which caused respiratory
      infections. Thus, using this technique, a positive diagnosis was made in 68.2% of
      cases, of which 49.2% were positive by the hemagglutination and complement
      fixation reactions, too. The test specificity could have been higher if the
      pathological products had been prelevated within the first three days after the
      onset of the disease.

PMID- 9558969
TI  - Prevalence of tsetse fly and ruminant trypanosomosis in Katsina-Ala Local
      Government Area, Nigeria.
AB  - The prevalence of ruminant trypanosomosis and tsetse flies was investigated in
      Katsina-Ala Local Government Area--a sleeping sickness endemic area--between the
      valleys of River Benue, Katsina-Ala and Donga in Central Nigeria. Analysis of
      three hundred and twenty blood samples showed that among semi-nomadic animals,
      about one cattle (21.3%; 0.213, confidence interval C1 +/- 0.06) and two sheep
      (38.0%; 0.380, C1 +/- 0.10) out of five carried mature trypanosome infections.
      Significantly lower (P < 0.05) values (12.5%; 0.125, C1 +/- 0.08) were recorded
      among peri-domestic West African Cross Red Sokoto (WAD x RS) goats. Trypanosoma
      vivax was the most prevalent species encountered; it was diagnosed in 10.3% of
      the ruminant population and responsible for 42.8% of the infections in all
      animals. Corresponding figures for T. congolense were 5.9% and 24.6%,
      respectively. T. brucei infections were low in cattle (1.8%) and absent in goats.
      Males and young stock had lower infection but the difference was not significant
      (P > 0.05) except between the ages in cattle. Glossina tachinoides was the only
      tsetse species encountered and responded to acetone odour attractant in biconical
      traps.

PMID- 9558970
TI  - [Cytological observations on the protozoan Pneumocystis carinii].

PMID- 9558971
TI  - Modulation of cell adhesion by tyrosine kinases and phosphatases inhibitors.
AB  - Integrin-mediated activation of monocytes is an important aspect involved in the
      increase of proinflammatory cytokine messages. Tyrosine phosphorylation of
      proteins is one of the earliest events involved in these processes: Therefore, we
      selected two inhibitors, one for tyrosine kinases (quercitin) and another for
      tyrosine phosphatases (sodium orthovanadate) and we studied their capacity to
      modulate monocyte adhesion to fibronectin. Our results showed that quercitin
      strongly inhibits both tyrosine phosphorylation and cell adhesion. Sodium
      orthovanadate induces a modest increase of tyrosine phosphorylation and a weak
      enhancement of cell adhesion. When a combination of the two inhibitors was used,
      the tyrosine phosphorylation level displayed a strong enhancement. In contrast,
      cell adhesion was inhibited, but to the same degree. These observations indicate
      that tyrosine kinases may be more important than tyrosine phosphatases in the
      modulation of cell adhesion by flavonoid compounds.

PMID- 9558972
TI  - Experimental studies on bacterial product CANTASTIM derived from Pseudomonas
      aeruginosa. II. Protective effect in Salmonella typhimurium infection.
AB  - Stimulation of the host defense system in a nonspecific way may provide effective
      treatment of recurrent infections. CANTASTIM is a bacterial product that has been
      successfully used in cancer immunotherapy as well as in chronic infections
      treatment. The nonspecific protective effect of CANTASTIM was investigated in two
      models of experimental infection with Salmonella typhimurium in mice.
      Prophylactic administration of CANTASTIM (three days before challenge) enhanced
      peritoneal macrophages bactericidal activity and significantly increased survival
      of treated mice. When CANTASTIM was administered 72 h after bacterial challenge,
      in a sublethal infection model with Salmonella typhimurium, by activating
      macrophages, NK and T cells, it increased the survival rate. The cell populations
      and molecular mechanisms involved in the prophylactic and therapeutic protective
      effect CANTASTIM seem to be partially different.

PMID- 9558973
TI  - Experimental studies on the bacterial product CANTASTIM derived from Pseudomonas
      aeruginosa. III. Suppression of lipopolysaccharide-induced tumor necrosis factor
      alpha: are the lipid components involved?
AB  - We previously reported that the bacterial immunomodulator CANTASTIM inhibited the
      LPS-induced TNF-alpha production in murine macrophages both in vivo and in vitro.
      In this report, we compared the activity of CANTASTIM with that of two
      phospholipids (cardiolipin and phosphatidylethanolamine) which are among the
      components of its lipid fraction. We noticed a significant reduction in the
      production of TNF-alpha upon stimulation with LPS in murine peritoneal
      macrophages pretreated for at least 3 h with CANTASTIM or cardiolipin. CANTASTIM
      was active at much lower concentrations than cardiolipin. Preliminary experiments
      with partially deacylated CANTASTIM indicated some decrease of TNF-alpha
      secretion. However, further studies are necessary to clarify this matter. Also,
      while CANTASTIM and its partially deacylated derivative could trigger the TNF
      alpha secretion in murine macrophages, individual phospholipids did not. Based on
      these results, we concluded that CANTASTIM could induce the TNF-alpha suppression
      by multiple mechanisms, including the induction of regulatory cytokines such as
      IL-10 and CD14 receptor blockade/downregulation.

PMID- 9558974
TI  - Experimental studies on bacterial product CANTASTIM derived from Pseudomonas
      aeruginosa with immunomodulatory properties. IV. Tyrosine phosphorylation as an
      effect of stimulation on different cell populations.
AB  - The bacterial product derived from Pseudomonas aeruginosa (trade mark-CANTASTIM)
      proved immunomodulatory effects in different systems, both in vitro and in vivo
      experimental animal models, as well as in clinical trials. Among the results
      obtained regarding CANTASTIM, the following immunomodulatory properties could be
      mentioned: an increase of the activated T cell subpopulations and humoral
      mediated immune processes, facilitation of phagocytic processes, stimulation of
      cytotoxic activity reflected in the improvement of the capacity of defense in
      several tumoral and infectious diseases. To better elucidate the intimate
      mechanisms by which CANTASTIM modulates the cellular functions on different
      cellular populations, we used tyrosine phosphorylation as an estimate of cell
      activation on peripheral blood lymphocytes (PBL) and a monocyte cell line (THP
      1). In PBL, the treatment with CANTASTIM renders them more susceptible to CD3
      stimulation than non-treated cells. In monocytes, CANTASTIM and two phospholipid
      components of CANTASTIM modulated in a different manner the cellular adhesion on
      fibronectin and tyrosine phosphorylation leading to the conclusion that these
      phospholipid components do not fully explain CANTASTIM modulatory properties on
      cell adhesion processes.

PMID- 9558975
TI  - Modulation of CD14 expression on human granulocytes by a bacterial product
      "Cantastim" derived from Pseudomonas aeruginosa.
AB  - Pathophysiological effects of infection with Gram-negative bacteria depend on
      recognition by host cells of LPS, a major component of the outer membrane of
      these microorganisms. CD14 is an immunological marker and also the receptor for
      LPS on phagocytic cells. The aim of the present study was to investigate the
      capacity of a bacterial immunomodulator, named Cantastim, which is used as a
      therapeutical agent in neoplasic diseases and chronic infections, to modulate the
      CD14 expression on human granulocytes. Our preliminary results showed that
      Cantastim can not influence the expression of CD14 on granulocytes obtained from
      healthy donors, but on the other hand Cantastim was able in vitro and in vivo to
      down-regulate the expression of this marker on granulocytes from a patient with
      neoplasic disease.

PMID- 9558976
TI  - Application of ELISA with antigenic glycolipids in early diagnosis of pulmonary
      tuberculosis.
AB  - Antibodies against M. tuberculosis antigenic glycolipids were determined by
      enzyme-linked immunosorbent assay (ELISA) in 80 sera from patients suspected of
      pulmonary tuberculosis, with suggestive clinical signs and radiological
      abnormalities, but smears negative. The test was also performed on 68 control
      sera from patients with bacteriologically confirmed pulmonary tuberculosis, in
      different stages of disease. We obtained the test sensitivity of 89.5% for the
      confirmed tuberculosis patient sera. Low levels of specific antibodies and the
      sensitivity of 75% were found when using ELISA in smears negative patients at the
      onset of clinical tuberculosis. The experimental results showed that ELISA could
      be used as a supporting test in early diagnosis of pulmonary tuberculosis.

PMID- 9558977
TI  - Interactions between Borrelia burgdorferi and eukaryote cells: comparative
      ultrastructural aspects.
AB  - In the present study, mammalian VERO cells, human polymorphonuclear leukocytes
      (PMN) and mouse peritoneal macrophages (MPM) were coincubated with B31 Borrelia
      burgdorferi strain (Bb) and examined by transmission electron microscopy. The
      results indicate that the spirochete adheres to the mammalian cells mainly by the
      apical pole and less frequently by the lateral wall. In VERO cells and MPM cell
      penetration is accomplished especially by cytoplasmic membrane destruction, the
      spirochete appearing free in the cytoplasm, but also by phagocytosis. In this
      latter case the pathogen is seen in phagosome. In PMN the internalization takes
      place exclusively by phagocytosis, the spirochete undergoing destruction in
      phagosomes. Sometimes an alteration of the phagosomal membrane is observable,
      probably produced by the pathogen as a mechanism to avoid fusion with the
      lysosome. Other aspects indicate the contribution of the parasitized cell
      cytoskeleton to the spreading of Borrelia to adjacent cells. MPM does not
      represent a very efficient barrier against Bb, as can be seen from the cellular
      behaviour of the spirochetes in this study, PMN seems to a more efficient
      barrier, by its unique capacity to destroy the microorganism after phagocytosis.

PMID- 9558978
TI  - Macromolecular synthesis and ultrastructural changes induced in human larynx
      carcinoma cells following photodynamic therapy in vitro.
AB  - Human larynx carcinoma cells (HEp2) were sensitized with different concentrations
      of Hematoporphyrin and irradiated with a He-Ne laser at different fluences. The
      degree of PDT-effects were estimated by two parameters: a) macromolecular
      synthesis and b) observations using electron microscopy. All experiments were
      evaluated after 68 hr at 37 degrees C. The results showed that PDT exposure of
      HEp2 cells is characterized by: 1) inhibition of macromolecular synthesis and 2)
      different cellular and subcellular lesions. Summing up, these studies indicate
      the existence of a strong correlation between different PDT exposures and the
      degree of biochemical and ultrastructural changes in human larynx carcinoma cells
      in vitro.

PMID- 9558979
TI  - Freeze-drying of some strains of biotechnological interest (Aureobasidium
      pullulans).
AB  - Optimal freeze-drying conditions for Aureobasidium pullulans were investigated.
      Protective substances were used to compensate for the stress reported during
      freezing (gelatin, calf serum) and desiccation (saccharose, raffinose,
      trehalose), used in different combinations.

PMID- 9558980
TI  - Prevalence of hepatitis B and C virus markers among the members of the medical
      sanitary staff from the Faculty of Dentistry "Carol Davila" University of
      Medicine and Pharmacy, Bucharest.
AB  - This study was developed in an attempt to estimate the prevalence of hepatitis B
      and C virus markers in the sanitary personnel from dentistry clinics which
      represents a high risk group concerning both contamination and transmission of
      the infection. The results of the study showed a higher contamination by virus B
      than virus C. The distribution of contamination depending upon the position held
      by the staff members revealed a higher contamination incidence among medium level
      personnel than among high level personnel. The need to initiate this study is due
      to the high incidence of contamination with hepatitis B virus which calls for the
      implementation of prophylaxis measures to protect both the medical personnel and
      the patients.

PMID- 9558981
TI  - A hypertension treatment update

PMID- 9558982
TI  - New ways to protect your vision

PMID- 9558983
TI  - Does dietary fat still matter?

PMID- 9558984
TI  - Coping with cancer fatigue

PMID- 9558985
TI  - Aspirin and NSAIDs. Is aspirin safe to take with another nonsteroidal anti
      inflammatory?

PMID- 9558986
TI  - Treating a seizure. What follow-up do I need after a first seizure?

PMID- 9558987
TI  - Stiff neck. Recently, I've had several bouts with a stiff neck. Should I be
      worried?

PMID- 9558988
TI  - US sees first legal case of physician assisted suicide.

PMID- 9558989
TI  - BMA calls for smoking to be banned in public places.

PMID- 9558991
TI  - Rapid HIV testing urged in the US.

PMID- 9558990
TI  - German doctors vote to prescribe heroin to misusers.

PMID- 9558992
TI  - Florida doctor is investigated over experimental treatment.

PMID- 9558994
TI  - Commentary: grounded theory and the constant comparative method.

PMID- 9558995
TI  - Intravascular volume optimisation during repair of proximal femoral fracture.
      Intravascular volume was depleted perioperatively in control group.

PMID- 9558996
TI  - Intravascular volume optimisation during repair of proximal femoral fracture.
      Differences in outcome were probably due to chance.

PMID- 9558997
TI  - Working in management. Doctors do better financially than managers do.

PMID- 9558998
TI  - Working in management. Having public health doctors as managers is not the
      solution.

PMID- 9558999
TI  - Drug and Therapeutics Bulletin defends its stance over donepezil.

PMID- 9559001
TI  - Breast feeding does not always work. All mothers should be offered help and
      support to breast feed.

PMID- 9559000
TI  - Rationing health care. Patients need to be prioritised.

PMID- 9559002
TI  - Breast feeding does not always work. Various supplements to breast feeding are
      possible.

PMID- 9559003
TI  - The disorganized state of primary care.

PMID- 9559004
TI  - Cross-disciplinary training: time to remove the blinders.

PMID- 9559005
TI  - Princess Diana's tragic legacy.

PMID- 9559006
TI  - Familial abuse: a multifaceted problem.

PMID- 9559007
TI  - Familial abuse: a multifaceted problem.

PMID- 9559008
TI  - Overpopulation and Rwanda.

PMID- 9559009
TI  - Helicobacter pylori.

PMID- 9559010
TI  - Breast self-examination techniques.

PMID- 9559011
TI  - Fluoridation and fracture.

PMID- 9559012
TI  - Trends and variations in length of hospital stay for childbirth in Canada.
AB  - BACKGROUND: Early discharge after childbirth is widely reported. In this study
      the authors examined trends in maternal length of hospital stay in Canada from
      fiscal year 1984-85 through fiscal year 1994-95. They also examined variations in
      length of stay in 1994-95 in most of the Canadian provinces and the territories.
      METHODS: Epidemiologic analyses of the temporal and geographic variations in
      maternal length of hospital stay in Canada from 1984-85 to 1994-95 (even years
      only), based on hospital discharge data collected by the Canadian Institute for
      Health Information, with a total of 1,456,800 women for the 6 study years.
      RESULTS: Mean length of hospital stay decreased during the decade, from 5.3 days
      in 1984-85 to 3.0 days in 1994-95, with similar trends for both cesarean and
      vaginal delivery. The decrease resulted from both increasing rates of short stay
      (less than 2 days) and decreasing rates of long stay (more than 4 days).
      Substantial temporal and interprovincial variations in several medical and
      obstetric complications were also observed but did not explain the corresponding
      variations in length of stay. The reduction in length of hospital stay was not
      restricted to uncomplicated cases: there was an equivalent decrease in cases with
      complications. In 1994-95 the average length of hospital stay in Alberta was 2.6
      days, 0.3 to 1.7 days shorter than in the other provinces and the territories.
      INTERPRETATION: Length of hospital stay for childbirth has decreased
      substantially in Canada in recent years, but there remain important
      interprovincial variations. These trends and variations are not likely due to
      changes or differences in patient-specific factors.

PMID- 9559014
TI  - Safe motherhood: can we make a difference?

PMID- 9559013
TI  - Surviving social assistance: 12-month prevalence of depression in sole-support
      parents receiving social assistance.
AB  - BACKGROUND: Although it is generally recognized that poverty and depression can
      coexist among single parents receiving social assistance, there is insufficient
      research on this topic. The goals of this study therefore were to investigate the
      prevalence, correlates and health care expenditures associated with depression
      among sole-support parents receiving social assistance. METHODS: Sole-support
      parents who had applied for social assistance in 2 regions of southwestern
      Ontario were included in the study. Depression was diagnosed with the 1994
      University of Michigan Composite International Diagnostic Interview short forms.
      RESULTS: The 12-month prevalence rate of depressive disorder among the parents
      interviewed was 45.4% (345/760). A total of 247 (32.5%) had major depressive
      disorder alone, 19 (2.5%) had dysthymia, and 79 (10.4%) had both major depressive
      disorder and dysthymia ("double depression"). Those with major depressive
      disorder, particularly double depression, had significantly higher rates of
      coexisting psychiatric disorder than those without depressive disorders. Parents
      with depression reported higher rates of developmental delay and behaviour
      problems in their children than parents without depression. Expenditures for
      health care services were higher for parents with depression and for their
      children than for parents without depressive disorder and their children.
      INTERPRETATION: Single parents receiving social assistance have high rates of
      depression. Such parents with depression also have higher rates of other
      psychiatric disorders and higher expenditures for health care services, and their
      children have higher rates of developmental delay and behaviour problems.

PMID- 9559015
TI  - Society's interest in protection for the fetus.

PMID- 9559016
TI  - Unconventional therapies for cancer: 1. Essiac. The Task Force on Alternative
      Therapies of the Canadian Breast Cancer Research Initiative.
AB  - Physicians and patients have been frustrated by the lack of reliable information
      on unconventional therapies. To help fill this gap in the area of breast cancer
      therapy, the Canadian Breast Cancer Research Initiative formed a task force to
      advise it on how best to promote research into unconventional therapies. As part
      of the work of the task force, a review of the available literature was carried
      out for each of the following products: Essiac, green tea, Iscador, hydrazine
      sulfate, vitamins A, C and E, and 714-X. The first article in this series on
      unconventional therapies for cancer describes the methodology used to obtain and
      evaluate the information and provides a summary of the findings on Essiac.
      Subsequent articles will cover the other products. For most of the products
      reviewed, there has been some indication of possible benefit but no definitive
      evidence. Innovative and collaborative research needed to meet the information
      needs of growing numbers of patients and their physicians is now being sponsored
      by the Canadian Breast Cancer Research Initiative. Open communication between
      patients and physicians is also necessary for the maintenance of an appropriate
      therapeutic partnership and for the identification and control of side effects.
      The Ontario Division of the Canadian Cancer Society, a partner in the Canadian
      Breast Cancer Research Initiative, supported the preparation of a patient
      information piece on unconventional therapies to accompany the series. This item
      will assist patients who are considering such therapies and will promote open
      communication between patients and their physicians.

PMID- 9559017
TI  - [The physician's professional competence and ethics education].

PMID- 9559019
TI  - MDs aiming for hospital boardroom may face humbling experience, CEO warns.
      Interview by Patrick Sullivan.

PMID- 9559018
TI  - Of mice and mostly men--hantavirus pulmonary syndrome.

PMID- 9559020
TI  - The brutal politics of health care.
AB  - The 1998 federal budget received less than glowing reviews for its provisions
      regarding health care, but Charlotte Gray says this lack of health care
      initiatives should surprise no one. After all, there won't be a federal election
      for another 3 years.

PMID- 9559021
TI  - Malpractice concerns lead to unprecedented cooperation as CMPA, CMA seek answers.

PMID- 9559022
TI  - Alendronate-induced esophagitis.

PMID- 9559023
TI  - Alzheimer's disease.

PMID- 9559024
TI  - Geriatrics photo quiz. Horner's syndrome.

PMID- 9559025
TI  - Red lesion on chest wall.

PMID- 9559026
TI  - Thyroid dysfunction: how to manage overt and subclinical disease in older
      patients.
AB  - Thyroid dysfunction is relatively common in older patients, but its clinical
      presentation varies. It may be obvious from the classic presenting symptoms, or
      it may be asymptomatic and discovered incidentally during routine testing. The
      clinical diagnosis of hypothyroidism and hyperthyroidism can be difficult in
      older patients, because many of the usual symptoms may be mistaken for the
      effects of aging or other medical conditions. Even so, these diseases in their
      overt forms are always significant and require treatment. On the other hand,
      subclinical hypo- and hyperthyroidism are often incidental biochemical
      abnormalities that may or may not require intervention.

PMID- 9559027
TI  - Type 2 diabetes: treatment goals and pharmaceutical therapies. 2.
AB  - The most important treatments for type 2 diabetes remain weight reduction and
      physical activity, but an increasing armamentarium of drug therapies has much
      improved our ability to control blood glucose levels. Each of the known metabolic
      defects in type 2 diabetes can now be treated by different classes of drugs.
      Although the side effects of these drug therapies are relatively mild and
      infrequent, physicians need to be on guard for possible problems. Primary care
      physicians can manage most patients with type 2 diabetes. Specialists in
      endocrinology, ophthalmology, and podiatry are valuable resources.

PMID- 9559028
TI  - Management strategies for problem behaviors in the patient with dementia.
AB  - Psychiatric and behavioral problems are present in most patients with dementia
      and are usually the clinician's main focus of management. Differential diagnosis
      of these problems can be challenging, but the effort is essential for planning
      appropriate therapy. Pharmacologic interventions are available for treatment of
      depression, agitation, aggression, psychotic symptoms, wandering, and sleep
      disorders. Given the less than favorable risk-benefit ratio of most psychotropic
      drugs in the population of older patients with dementia, the importance of
      nonpharmacologic strategies and limiting treatment goals should not be
      overlooked.

PMID- 9559029
TI  - How the principles of geriatric assessment are shaping managed care.
AB  - In traditional geriatric medicine, comprehensive assessment is considered crucial
      to the care of frail older patients. The principles of geriatric assessment-
      identifying high-risk patients and targeting them for preventive interventions-
      are also practiced by managed care organizations (MCOs). Self-reported health
      surveys and administrative data are two methods used by MCOs to identify members
      at high risk for adverse health outcomes and functional decline who may benefit
      from geriatric case management. For a successful partnership with primary care
      physicians, it is very important that geriatric care managers should be
      knowledgeable in the principles of geriatric medicine.

PMID- 9559030
TI  - Ramsay Hunt syndrome: a challenging herpes zoster virus infection.

PMID- 9559031
TI  - Mayo Committee Governance System.

PMID- 9559032
TI  - Barriers to cancer screening in Mexican-American women.
AB  - OBJECTIVE: To test the simultaneous effect of various established predictors of
      breast and cervical cancer screening (breast self-examination, clinical breast
      examination by a physician, Papanicolaou [Pap] smear, and pelvic examination) in
      a low-income, Mexican-American sample. MATERIAL AND METHODS: A total of 188
      Mexican-American women participated in a face-to-face structured interview in
      their preferred language. We tested a model with four established predictors of
      breast and cervical cancer screening--communication skills, knowledge of cancer,
      access to health care (finances and availability of care), and anxiety about
      cancer. Simultaneous structural equations analysis was used to form latent
      variables and to control for the effect of all predictors concurrently. RESULTS:
      Screening behavior was inversely associated with anxiety about cancer when all
      other predictors were statistically controlled. In addition, anxiety
      substantially affected the relationship between communication skills and
      screening behavior. Unexpectedly, knowledge of cancer was positively, rather than
      negatively, associated with anxiety about cancer. Predictors in the model
      demonstrated an excellent fit of the proposed model to the data. CONCLUSION:
      Successful cancer screening programs for Mexican-American women must address not
      only access barriers but also communication skills, knowledge, and, perhaps most
      importantly, anxiety.

PMID- 9559033
TI  - Long-term outcome of patients who undergo tonometry as part of a general physical
      examination.
AB  - OBJECTIVE: To determine the value of including tonometry as part of a general
      physical examination. MATERIAL AND METHODS: Between Feb. 14, 1977, and Dec. 31,
      1980, 849 residents of Rochester, Minnesota, underwent measurement of intraocular
      pressure by trained ophthalmic technicians at the request of a nonophthalmologist
      physician as part of a general physical examination. In 1995 and 1996, these
      cases were reviewed to determine how many patients in this study cohort had
      subsequently been diagnosed as having glaucoma. The outcome was derived from the
      examination of medical records and from the responses to mailed questionnaires
      and telephone interviews with study patients and their physicians. RESULTS: In
      patients whose intraocular pressures were less than 16 mmHg at baseline, the risk
      of being diagnosed as having glaucoma within 10 years was 1% (95% confidence
      interval [CI], 0 to 2%) and within 15 years was 2% (95% CI, 0 to 4%). In patients
      whose pressure in the higher-pressure eye was 16 to 21 mmHg at baseline, the risk
      of having glaucoma in 10 years was 3% (95% CI, 2 to 5%) and in 15 years was 5%
      (95% CI, 3 to 7%). Twenty-four patients were found at baseline to have an
      intraocular pressure of 22 mmHg or higher in at least one eye or a difference of
      5 mmHg or more between the two eyes. In this group, the risk of having glaucoma
      in 10 years was 17% (95% CI, 0 to 31%) and in 15 years was 26% (95% CI, 6 to
      43%). CONCLUSION: When included as part of a general physical examination of
      older persons, tonometry and a few simple questions provide information that can
      be used to help the clinician determine the advisability of more detailed
      ophthalmic examinations.

PMID- 9559034
TI  - Clinical determinants of hemodynamic and symptomatic responses in 2,000 patients
      during adenosine scintigraphy.
AB  - OBJECTIVE: To determine whether subsets of patients referred for a clinically
      indicated radionuclide adenosine stress study respond differently to a standard
      infusion of adenosine. MATERIAL AND METHODS: We assessed multiple clinical and
      hemodynamic variables in the first 2,000 patients who underwent adenosine
      perfusion studies in our laboratory. A relevant clinical variable was defined as
      one that was significantly associated with changes in heart rate and blood
      pressure during adenosine infusion. Relevant clinical variables that were most
      significantly related to hemodynamic variables included age, gender, rhythm
      (atrial fibrillation), diabetes, and left ventricular function. These variables
      were then related to symptomatic responses (adverse effects) to adenosine
      infusion. To determine whether the different peripheral responses to adenosine
      reflected clinically important differences in coronary vasodilatation, we
      compared perfusion imaging with coronary angiographic findings in the 408
      patients who underwent both studies within 6 months of each other. RESULTS: The
      decrease in systolic blood pressure was greater and the reflex tachycardia was
      less in patients 70 years of age or older and in those with insulin-dependent
      diabetes in comparison with younger patients and those without type 1 diabetes.
      Men had smaller decreases in blood pressure and smaller increases in heart rate
      than did women. Patients with atrial fibrillation and those with left ventricular
      ejection fraction less than 40% had smaller decreases in blood pressure and
      smaller increases in heart rate than did those in sinus rhythm or those with an
      ejection fraction of 40% or more. Age 70 years or older, male gender, atrial
      fibrillation, and left ventricular ejection fraction less than 40% were
      associated with fewer symptoms and less severe chest pain in comparison with
      patients without these variables. For patients with coronary angiograms, the
      relationship between coronary artery disease evident on angiography and perfusion
      abnormalities noted on scintigraphy was not different for any of the relevant
      clinical variables. CONCLUSION: Common clinical patient subsets are associated
      with different peripheral hemodynamic and symptomatic responses to infusion of
      adenosine. Despite these observations, however, the ability to detect coronary
      artery disease with perfusion imaging is not obviously altered.

PMID- 9559035
TI  - Hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, codon 143
      CAC-->TAC--a variant with altered oxygen affinity that compromises measurement of
      glycated hemoglobin in diabetes mellitus: structure, function, and DNA sequence.
AB  - OBJECTIVE: To determine the nature and characteristics of a unique hemoglobin
      variant that causes a spurious increase in glycated hemoglobin (HbA1c). MATERIAL
      AND METHODS: Blood specimens from four unrelated persons with this hemoglobin
      variant were examined by conventional laboratory methods, including
      electrophoresis, high-performance ion-exchange chromatography, and isoelectric
      focusing; by amino acid sequence analysis, polymerase chain reaction-based DNA
      sequence analysis, and electrospray ionization mass spectrometry, to establish
      the molecular structure; and by studies of oxygen affinity under varied
      conditions, to define the functional characteristics of the hemoglobin variant.
      RESULTS: The unique hemoglobin variant observed in these four cases is due to the
      mutation CAC-->TAC, at beta-globin gene codon 143, corresponding to beta 143
      (H21) His-->Tyr. This amino acid substitution affects an important 2,3
      diphosphoglycerate binding site and slightly increases the oxygen affinity of the
      hemoglobin variant. CONCLUSION: A hitherto unrecognized hemoglobin variant,
      encountered in four unrelated persons of Irish or Scots-Irish ancestry,
      hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, has now been
      characterized at the molecular, structural, and functional levels. Although it is
      associated with a slight increase in oxygen affinity, it is without hematologic
      effect, and its only clinical significance is that it coelutes with HbA1c on ion
      exchange chromatography and thereby causes a spurious increase in HbA1c and
      compromises the use of this analyte to monitor the treatment of diabetes
      mellitus.

PMID- 9559036
TI  - Major depression in medically ill patients.
AB  - Major depression is one of the most common psychiatric problems complicating the
      treatment and prognosis of patients with active medical illness. Recognizing and
      treating major depressive conditions in this population can often be challenging,
      even for the most seasoned clinicians. This article reviews the medical and
      neurologic conditions that have been associated with the high prevalence rates of
      major depression. Highlights of the evaluation process that help confirm this
      suspected diagnosis are addressed, and management issues are discussed. Brief
      reviews of supportive psychotherapeutic tools that the clinician may find helpful
      are included, as well as current advances in pharmacologic interventions.

PMID- 9559037
TI  - Coinfection with Babesia microti and Borrelia burgdorferi in a western Wisconsin
      resident.
AB  - A 68-year-old woman, who had not traveled outside of western Wisconsin, was
      hospitalized after 4 weeks of chills, fevers, myalgias, neuralgias in her right
      arm, and pain in the right upper quadrant of her abdomen. Physical examination
      revealed hepatosplenomegaly, and laboratory studies showed anemia,
      thrombocytopenia, increased aspartate transaminase level, and microscopic
      hematuria. Wright's stain of a blood smear revealed intraerythrocytic organisms
      consistent with Babesia species. A polymerase chain reaction of whole blood
      specimens along with an increased serologic titer confirmed the diagnosis of
      Babesia microti. Indirect immunofluorescent antibody serology and Western blot
      analysis revealed a simultaneous infection with Borrelia burgdorferi. Coinfection
      with B. microti and B. burgdorferi may occur in endemic areas where both
      organisms are carried by the same tick vector, Ixodes scapularis. The intensity
      and duration of illness seem to be greatest in patients with concurrent
      infection.

PMID- 9559038
TI  - Esophagogastric hematoma mimicking a malignant neoplasm: clinical manifestations,
      diagnosis, and treatment.
AB  - Esophagogastric hematoma is a rare condition occurring spontaneously or after
      esophageal instrumentation. In this report, we describe a patient with acute
      dysphagia in whom a lower esophageal mass was detected radiographically. Upper
      endoscopy revealed an esophageal mass that extended from the mid-esophagus to the
      gastroesophageal junction and was associated with a malignant-appearing ulcerated
      mass (5 to 6 cm) in the cardia. Gastric cancer with esophageal extension was the
      presumptive diagnosis. Computed tomography showed that the esophageal mass had a
      density similar to blood, a finding suggesting the presence of an esophageal
      hematoma. Biopsy specimens of the ulcer revealed acute inflammation but no
      malignant involvement. The patient was treated conservatively, and the initial
      symptoms resolved. Esophagogastric hematomas can mimic a neoplasm; thus,
      establishing the correct diagnosis is important because this condition has a
      favorable prognosis, and only conservative treatment is needed.

PMID- 9559040
TI  - Clinician's guide to hepatitis C.
AB  - Hepatitis C virus infection is common, often silent, and almost always chronic
      and can lead to cirrhosis and hepatocellular cancer. Deaths related to chronic
      hepatitis C are expected to increase dramatically in the future. Many cases of
      infection are asymptomatic and are undiagnosed because of a lack of recognition
      by patients and physicians. All patients currently or previously at risk of
      infection should undergo screening, including those who received blood
      transfusions before 1992. Interferon is the only effective therapy, but
      disappearance of virus is sustained in only 10 to 15% of patients. The
      combination of interferon and oral ribavirin therapy may increase the sustained
      response rate to about 40%. New agents such as hepatitis C virus-specific
      protease inhibitors may be available in the next 5 to 10 years, and treatment is
      evolving toward multiple-drug regimens analogous to those used for human
      immunodeficiency virus (HIV) infection. In contrast to public funding for drug
      development in HIV, such funding for hepatitis C has been limited.

PMID- 9559041
TI  - Wilkins, Crick, and Watson: Nobel Prize for work on the structure of DNA.

PMID- 9559039
TI  - Theophylline: recent advances in the understanding of its mode of action and uses
      in clinical practice.
AB  - Theophylline, a drug that has been used for several decades, has several
      different actions at a cellular level, including inhibition of phosphodiesterase
      isoenzymes, antagonism of adenosine, enhancement of catecholamine secretion, and
      modulation of calcium fluxes. Recently, theophylline was found to have several
      immunomodulatory and anti-inflammatory properties, and thus interest in its use
      in patients with asthma has been renewed. The use of theophylline in the
      treatment of asthma and chronic obstructive pulmonary disease has diminished with
      the advent of new medications, but theophylline remains beneficial, especially in
      the patient with difficult refractory symptoms. In the future, theophylline may
      be used as treatment for bradyarrhythmias after cardiac transplantation,
      prophylactic medication to reduce the severity of nephropathy associated with
      intravenous administration of contrast material, therapy for breathing problems
      during sleep, and treatment for leukemias.

PMID- 9559042
TI  - A 31-year-old man with fever, dyspnea, and pulmonary infiltrates.

PMID- 9559043
TI  - Immune cholangitis: liver allograft rejection and graft-versus-host disease.
AB  - A pronounced similarity exists between liver allograft rejection and graft-versus
      host disease (GVHD) in the damage and eventual destruction of small intrahepatic
      bile ducts. Although an immunologic reaction has an important role, precisely
      identifying the target antigens or reason for persistence of the immune response
      has been difficult. An important difference between GVHD and liver rejection is
      the development of obliterative arteriopathy only in rejection. The three main
      histopathologic features of acute rejection are a predominantly mononuclear but
      mixed portal inflammation, subendothelial inflammation of portal or terminal
      hepatic veins (or both), and bile duct inflammation and damage. In acute
      rejection, a controversial issue is determining when therapeutic intervention is
      needed. The recommended approach is to base treatment on a combination of
      histopathologic changes and liver injury or dysfunction. Chronic rejection, which
      usually does not occur before 2 months after transplantation, is characterized by
      two main histopathologic features: (1) damage and loss of small bile ducts and
      (2) obliterative arteriopathy. Acute GVHD begins within the first month after
      transplantation and most commonly involves the skin, gastrointestinal tract, and
      liver, whereas chronic GVHD usually develops more than 80 to 100 days after liver
      transplantation and affects 30 to 50% of long-term survivors. Recognition of the
      early, cellular stages of chronic GVHD is important in preventing irreversible
      damage.

PMID- 9559044
TI  - Ischemic cholangitis.
AB  - Ischemia-induced bile duct lesions have been collectively labeled as ischemic
      cholangitis. The biliary epithelium is dependent on arterial blood flow, unlike
      the hepatic parenchyma with its dual arterial and portal venous blood supply. As
      such, the biliary epithelium is susceptible to injury when arterial blood flow is
      compromised. This compromise can occur at the level of the major, named hepatic
      artery branches or at the microscopic, peribiliary capillary plexus level.
      Typically, ischemic cholangitis manifests as segmental strictures and
      cholangiectases with resultant mechanical impairment of bile flow and,
      occasionally, secondary infection of the biliary system. Ischemic cholangitis
      after liver transplantation is becoming an important problem and likely is
      attributable to numerous factors. Hepatic arterial infusion of chemotherapy and
      systemic vasculitis are other causes of ischemic cholangitis. The role of
      ischemia in other chronic biliary and ductopenic diseases remains speculative.

PMID- 9559045
TI  - Overcoming the barriers to cancer screening.

PMID- 9559046
TI  - Malignant pyoderma and Wegener's granulomatosis.

PMID- 9559047
TI  - Granulomatous vasculitis associated with herpes virus.

PMID- 9559048
TI  - Diabetic retinopathy. Screening and prevention of blindness. A doctoral thesis.
AB  - Diabetic eye disease is a major cause of blindness in the Western World and
      remains one of the most serious complications of diabetes mellitus. Retinopathy
      is the ocular complication of diabetes that most often leads to impaired vision.
      In recent years laser treatment has been introduced that can significantly
      decrease the likelihood of blindness in diabetic patients, if the eyes are
      treated at the appropriate stage of the disease. It remains a public health
      problem to make sure that each patient is treated at the optimal time in the
      development of the eye disease. Several types of screening programs have been
      designed throughout the world to meet this problem. We now report on our active
      screening program for diabetic eye disease and describe the sight and eye
      condition of the diabetic patients who have been involved in this program. In
      1980, regular eye screening for diabetic retinopathy was initiated at Department
      of Ophthalmology, Landakot Hospital. The number of diabetic patients seen
      regularly has increased considerably since then, with 70-80% of type 1 diabetic
      patients in the country participating in the program in 1990, increasing to over
      90% in 1994. About a fifth of type 2 diabetics in the country participated in the
      program in 1990. The patients have undergone annual eye examinations and fundus
      photography. Laser treatment is administered for proliferative retinopathy and
      diabetic macular edema according to the Diabetic Retinopathy Study and Early
      Treatment Diabetic Retinopathy Study criteria. In 1990, we embarked on a cross
      sectional study to evaluate the prevalence of retinopathy and visual impairment
      of the type 1 and type 2 patients participating in our program. At the time of
      study, 205 insulin-taking patients, with age at diagnosis of less than 30 years,
      participated in our screening program. Out of those, retinopathy was present in
      106 (52%), patients proliferative retinopathy in 26 (13%) and macular edema in 19
      (9%). Visual acuity of 196 patients (96%) was equal or better than 6/12 in their
      better eye, 6 patients (3%) had 6/18-6/36 in their better eye, and 2 patients
      (1%) had equal or worse than 6/60 in their better eye, or legally blind. We
      concluded that the prevalence of retinopathy and visual impairment in type 1
      diabetic patients in the country was low compared with other countries. In 1990,
      out of 245 diabetic patients with Type 2 diabetes, retinopathy was present in 100
      patients (41%), proliferative retinopathy had been present in 17 (7%) and 24
      (10%) had diabetic macular edema. A total of 224 patients (91%) had visual acuity
      equal or better than 6/12 in their better eye, 17 patients (7%) with 6/18-6/36 in
      their better eye, and 4 patients (1.6%) equal or worse than 6/60 in their better
      eye, or legally blind. We concluded that the prevalence of visual impairment of
      those type 2 diabetic patients participating in our screening program at the time
      of study was low compared with population-based studies from other countries. In
      1992 we examined ways to make the screening program more efficient by identifying
      subgroups at low risk for developing eye disease that required treatment and
      therefore needed less frequent screening. We studied whether diabetic eye disease
      screening programs could be trimmed by excluding children and examining diabetic
      patients without retinopathy every other year. We examined all children under the
      age of 15 at the time of study and went through the files of all patients under
      age 15 examined from 1980 to 1992 at our diabetic eye screening program. We also
      followed for two years the type 1 and type 2 diabetic patients found to have no
      retinopathy in 1990, establishing their retinopathy stage two years later. Our
      results indicated that diabetic children under the age of 12 do not need regular
      screening for eye disease. Biannual examinations seemed to suffice in type 1 and
      2 diabetic patients without retinopathy. (ABSTRACT TRUNCATED)

PMID- 9559049
TI  - Activated glutamate intermediate in the enzymatic synthesis of glutamine. 1960.

PMID- 9559050
TI  - Advances in the enzymology of glutamine synthesis.
AB  - Meister's proposal of a gamma-glutamyl-P intermediate in the glutamine synthetase
      reaction set the scene for understanding how the stepwise activation of the
      carboxyl group greatly increased its susceptibility toward nucleophilic attack
      and amide bond synthesis. Topics covered in this review include: the discovery of
      the enzymatic synthesis of glutamine; the role of glutamine synthetase in
      defining the thermodynamics of ATPases; early isotopic tracer studies of the
      synthetase reaction; the proposed intermediacy of gamma-glutamyl-phosphate; the
      mechanism of methionine sulfoximine inhibition; stereochemical mapping of the
      enzyme's active site; detection of enzyme reaction cycle intermediates;
      borohydride trapping of gamma-glutamyl-P; positional isotope exchanges catalyzed
      by glutamine synthetase; regulation of bacterial enzyme; and a brief account of
      how knowledge of the atomic structure of bacterial glutamine synthetase has
      clarified ligand binding interactions. Concluding remarks also address how the so
      called "Protein Ligase Problem" may be solved by extending the catalytic
      versatility of carboxyl-group activating enzymes.

PMID- 9559051
TI  - Hepatic glutamine transport and metabolism.
AB  - Although the liver was long known to play a major role in the uptake, synthesis,
      and disposition of glutamine, metabolite balance studies across the whole liver
      yielded apparently contradictory findings suggesting that little or no net
      turnover of glutamine occurred in this organ. Efforts to understand the unique
      regulatory properties of hepatic glutaminase culminated in the conceptual
      reformulation of the pathway for glutamine synthesis and turnover, especially as
      regards the role of sub-acinar distribution of glutamine synthetase and
      glutaminase. This chapter describes these processes as well as the role of
      glutamine in hepatocellular hydration, a process that is the consequence of
      cumulative, osmotically active uptake of glutamine into cells. This topic is also
      examined in terms of the effects of cell swelling on the selective stimulation or
      inhibition of other far-ranging cellular processes. The pathophysiology of the
      intercellular glutamine cycle in cirrhosis is also considered.

PMID- 9559052
TI  - Enzymes utilizing glutamine as an amide donor.
AB  - Amide nitrogen from glutamine is a major source of nitrogen atoms incorporated
      biosynthetically into other amino acids, purine and pyrimidine bases, amino
      sugars, and coenzymes. A family comprised of at least sixteen amidotransferases
      are known to catalyze amide nitrogen transfer from glutamine to their acceptor
      substrates. Recent fine structural advances, largely as a result of X-ray
      crystallography, now provide structure-based mechanisms that help to explain
      fundamental aspects of the catalytic and regulatory interactions of several of
      these aminotransferases. This chapter provides an overview of this recent
      progress made on the characterization of amidotransferase structure and
      mechanism.

PMID- 9559053
TI  - Mechanistic issues in asparagine synthetase catalysis.
AB  - The enzymatic synthesis of asparagine is an ATP-dependent process that utilizes
      the nitrogen atom derived from either glutamine or ammonia. Despite a long
      history of kinetic and mechanistic investigation, there is no universally
      accepted catalytic mechanism for this seemingly straightforward carboxyl group
      activating enzyme, especially as regards those steps immediately preceding amide
      bond formation. This chapter considers four issues dealing with the mechanism:
      (a) the structural organization of the active site(s) partaking in glutamine
      utilization and aspartate activation; (b) the relationship of asparagine
      synthetase to other amidotransferases; (c) the way in which ATP is used to
      activate the beta-carboxyl group; and (d) the detailed mechanism by which
      nitrogen is transferred.

PMID- 9559054
TI  - Mechanisms of cysteine S-conjugate beta-lyases.
AB  - Mercapturic acids are conjugates of S-(N-acetyl)-L-cysteine formed during the
      detoxification of xenobiotics and during the metabolism of such endogenous agents
      as estrogens and leukotrienes. Many mercaturates are formed from the
      corresponding glutathione S-conjugates. This chapter focuses on (a) the discovery
      of the cysteine S-conjugate beta-lyases; (b) the involvement of pyridoxal-5
      phosphate; (c) the influence of the electron-withdrawing properties of the group
      attached to the sulfur atom; and (d) the potential of cysteine S-conjugates as
      pro-drugs.

PMID- 9559055
TI  - gamma-Glutamyl transpeptidase: catalytic mechanism and gene expression.
AB  - The gamma-glutamyl transpeptidases are key enzymes in the so-called gamma
      glutamyl cycle involving glutathione synthesis, the recovery of its constituents,
      and in the transport of amino acids. This membrane-bound ectoenzyme thus serves
      to regulate glutathione synthesis. This chapter deals with the active site
      chemistry of gamma-glutamyl transpeptidase, including the role of side-chain
      groups on the light subunit as well as several serine residues in the catalytic
      process. Also considered are genomic studies indicating (a) the presence of a
      single gene in mouse and rat; (b) the occurrence of multiple genes in humans; (c)
      the involvement of multiple promoters for gene expression; and (d) how these
      multiple promoters may play a role in the tissue-specific expression of gamma
      glutamyl transpeptidases.

PMID- 9559056
TI  - Enzymology of bacterial lysine biosynthesis.
AB  - Bacteria have evolved three strategies for the synthesis of lysine from aspartate
      via formation of the intermediate diaminopimelate (DAP), a metabolite that is
      also involved in peptidoglycan formation. The objectives of this chapter are
      descriptions of mechanistic studies on the reactions catalyzed by
      dihydrodipicolinate synthase, dihydrodopicolinate reductase,
      tetrahydrodipicolinate N-succinyl-transferase, N-succinyl-L,L-DAP
      aminotransferase, N-succinyl-L,L-DAP desuccinylase, L,L-DAP epimerase, L,L-DAP
      decarboxylase, and DAP dehydrogenase. These enzymes are discussed in terms of
      kinetic, isotopic, and X-ray crystallographic data that allow one to infer the
      nature of interactions of each of these enzymes with its substrate(s), coenzymes,
      and inhibitors.

PMID- 9559057
TI  - Collagen hydroxylases and the protein disulfide isomerase subunit of prolyl 4
      hydroxylases.
AB  - Prolyl 4-hydroxylases catalyze the formation of 4-hydroxyproline in collagens and
      other proteins with an appropriate collagen-like stretch of amino acid residues.
      The enzyme requires Fe(II), 2-oxoglutarate, molecular oxygen, and ascorbate. This
      review concentrates on recent progress toward understanding the detailed
      mechanism of 4-hydroxylase action, including: (a) occurrence and function of the
      enzyme in animals; (b) general molecular properties; (c) intracellular sites of
      hydroxylation; (d) peptide substrates and mechanistic roles of the cosubstrates;
      (e) insights into the development of antifibrotic drugs; (f) studies of the
      enzyme's subunits and their catalytic function; and (g) mutations that lead to
      Ehlers-Danlos Syndrome. An account of the regulation of collagen hydroxylase
      activities is also provided.

PMID- 9559058
TI  - [The medical responsibility of an allergist].
AB  - The professional civil responsibility of an allergy physician should be restored
      to the more general framework of medical responsibility. This is at present the
      objective of considerable public debate. From now on it is known that the
      developments at present and to come for the most part go beyond the strict
      requirement of the juridical process. They take up fully a real choice of
      society. What place do we wish to give to physicians in the future? What new
      outlines relating to care should be adopted? What must be done for the victims of
      medical accidents? These are the fundamental questions that we ask ourselves
      today. The choices that apply, influence, must persuade our society, its made of
      action and the relationships between the various' components. It must be said
      that the stakes are enormous. It must also be said that all of this will not be
      achieved without clashes.

PMID- 9559059
TI  - [Masked and labelled food allergens].
AB  - Several food proteins are used as food additives or may be contained in foods as
      contaminants. These masked allergens are at high risk of inducing severe clinical
      reactions: acute asthma, laryngeal angioedema, anaphylactic shock or even death.
      The present regulation requires labelling only if the level of food ingredients
      is superior to 25% of the final product. Several immunologic methods can detect
      low levels of proteins, equal or inferior to 2%. However a level of 1% or less
      may be noxious, suggesting a need for a specific line of food products which
      could be guaranteed free of ... and which might be recommended to patients with
      food allergy.

PMID- 9559060
TI  - [Application of flow cytometry to the analysis of activation of human basophils.
      Immunologic validation of the method].
AB  - Among the different methods used for the analysis of human basophil activation as
      histamine and leukotriene release, flow cytometry presents several methodological
      advantages. Moreover, preliminary results obtained for a wide allergen panel have
      demonstrated its high sensitivity and specificity. We present here the results of
      the methods used to validate the flow cytometric analysis of human basophil
      activation by double anti-IgE FITC/anti-CD63 PE labelling of human leucocytes.
      The use of multiple labelling by monoclonals having different specificities have
      shown that the selected cells express the phenotype CD14-, CD19-, CD41- or +/-,
      CD45+, CD63- or +. This phenotype is related to human basophils. We have also
      demonstrated that the expression of CD63 is related to basophil activation and
      not to aggregated platelets which are also able to express this marker.

PMID- 9559061
TI  - [Testing basophil activation by flow cytometry in the diagnosis of allergy to
      hymenopteran venom].
AB  - Diagnosis of allergy to hymenoptera venom must be precise and depends on
      indisputable bio-clinical criteria, because of specific immunotherapy for
      indications such as systemic and/or anaphylactic reactions. Until nowadays,
      diagnosis was by specific IgE, histamine release and skin tests, most often done
      for the venoms of wasp, honey bee and hornet at the same time since, in 7-8 cases
      in 10 the patients had not identified the responsible insect. Basophil activation
      test (TAB) by Flux cytometry and measurement of leukotriene C4 (LTC4) are new
      techniques of great reliability. The work shows the correlations between the
      different immunobiological parameters by reference to TAB by CAF and measurement
      of LTC4. When the overall results for mixed venoms or those for single venoms are
      considered, the correlations between TAB, LTC4 and the other parameters are
      highly significant. It can now be considered objectively that TAB by CTF and
      measurement of LCT4 are the two highest-performing techniques for diagnosis of
      hymenoptera venom allergy and so validates them.

PMID- 9559063
TI  - [Contact eczema by proxy to benzoyl peroxide].

PMID- 9559062
TI  - [Antibiotic tolerance. Clinical and biological evaluation methods. Preliminary
      study of 42 patients].

PMID- 9559064
TI  - [Contact eczema to 17 beta estradiol].

PMID- 9559065
TI  - Female dispersal, social organization, and infanticide in langurs: are they
      linked to human disturbance?
AB  - Female dispersal in gregarious animals can involve the desertion of a site,
      desertion of a social group, or both. Group desertion may be related to
      inbreeding avoidance. Group fidelity may result from cooperation among females in
      a group. Site fidelity will be more likely when food can be monopolized and when
      the population density is close to habitat saturation. The degree of habitat
      saturation was approximated with a measure of human disturbance. The influence of
      these various factors on the incidence of female dispersal was investigated for
      langur populations using data from the literature. The results suggest that
      female dispersal in langurs involved site desertion, not group desertion. The
      incidence of female dispersal may affect the social organization of langurs. I
      propose that when females do not disperse, male takeovers prevail, whereas in
      populations where female dispersal regularly occurs bisexual groups are disbanded
      or new groups are formed, a process I call female split-merger. Male takeover is
      thought to occur when site fidelity is high, female split-merger when site
      fidelity is low. These processes were indeed found to occur in these
      circumstances. The dispersal of females might prevent infanticide, whereas male
      takeover might promote it. Indeed, in studies with male takeover, more infants
      fell victim to infanticide than in studies with female split-merger. Therefore,
      female dispersal in langurs is an effective female counterstrategy to
      infanticide. The factor that had the most profound effect on female dispersal,
      social organization, and infanticide was habitat saturation. Habitat saturation
      was measured as the degree of human disturbance, and its influence on the
      behavior of langurs is probably of relatively recent date. This may lead to an
      evolutionary transient situation and may explain the discrepancy between current
      socioecological theories and the behavior of langurs in populations lacking
      female dispersal.

PMID- 9559066
TI  - Chromosome diversity of the genus Aotus from Colombia.
AB  - Description of six Colombian karyomorphs is completed through an extensive
      cytogenetic characterization of 35 Aotus (owl monkeys) specimens. The description
      of a new karyomorph for Colombian Aotus by chromosome on Q, G, R, and C,
      sequential banding is included. Pairs of karyomorphs 2 and 3 and 6 and 9 with 2n
      of 54, and 50, respectively, as well as karyomorphs 7 and 8 with 46 and 58
      chromosomes were strongly suspected to represent different species on the grounds
      of large karyotypic differences. A proposal for a chromosome nomenclature of
      Aotus karyomorphs that aims to clarify Aotus taxonomy is presented which achieves
      a precise correspondence of different banding patterns, based on Q, G, R, and C
      sequential banding and chromosome measurements. Although our contribution is not
      a universal nomenclature system, unique criteria for chromosome denomination
      within Aotus karyomorphs are established. Previous systems of chromosome
      nomenclature have not successfully addressed the nomenclature of chromosomes of
      the same karyotype.

PMID- 9559067
TI  - [Spontaneous hematoma of the kidney. Apropos of 3 cases].
AB  - The objective of this study was to illustrate the diagnostic and therapeutic
      aspects of renal haematomas based on 3 cases observed in the Casablanca urology
      department and a review of the literature. In 50% of cases, the haematoma is
      secondary to adenocarcinoma or angiomyolipoma, requiring specific treatment.

PMID- 9559068
TI  - [Acute obstructive renal insufficiency and pregnancy. Apropos of a case].
AB  - Acute renal failure caused by obstruction by the gravid uterus is a rare
      complication of pregnancy. We report a case of obstructive acute renal failure in
      a patient at 28 weeks of gestation. Serum creatinine was 65 mg/l. Ultrasound
      examination showed a solitary right kidney. The course was marked by premature
      delivery. Renal function spontaneously returned to normal. This case suggests
      that acute obstructive uropathy should be considered to be a physiological
      phenomenon, especially on the right side.

PMID- 9559069
TI  - [Peritonitis due to spontaneous rupture of pyonephrosis. Apropos of a case].
AB  - Description of a case of peritonitis in a 60-year-old diabetic woman. Emergency
      laparotomy revealed a purulent effusion derived from a pyonephrotic and calculous
      left kidney. The patient was cured by left nephrectomy.

PMID- 9559070
TI  - [Enterococci as uropathogens. Frequency of isolation and sensitivity to
      antibacterial agents].
AB  - 221 clinically significant enterococcal strains (191: E. faecalis, 27: E.
      faecium, 3 others) were isolated from the urine of patients hospitalised with UTI
      over an 18-month period (1995-1996). The susceptibility of the isolates to 8
      antimicrobial agents was determined by agar dilution method (NCCLS). All
      enterococci were sensitive to vancomycin and most of them (over 92%) to
      penicillin and ampicillin. Only 3.14% of E. faecalis and 3.70% of E. faecium were
      resistant to ciprofloxacin. A relatively high incidence of resistance of
      enterococci to aminoglycosides was observed: 46.07% and 51.85% to streptomycin,
      42.41% and 44.44% to gentamicin, 70.68% and 77.78% to amikacin for E. faecalis
      and E. faecium, respectively. Among the resistant to penicillin and amino
      glycosides enterococci of the two species was found a great percent "high level"
      resistance. There were no beta-lactamase producers among our strains. The
      established multiresistance accompanied by "high level" resistance requires
      careful consideration of antimicrobial therapy of enterococcal UTI.

PMID- 9559071
TI  - [Retroperitoneal ganglioneuroma. Apropos of a case].
AB  - Ganglioneuroma is a rare tumour in adults. We report the case of a 26-year-old
      woman admitted in our department with right renal colic. Ultrasonography and
      computed tomography showed a heterogeneous retroperitoneal mass measuring 8 x 7
      cm in diameter and displacing the ureteropelvic junction and right kidney
      anteriorly and laterally. The preoperative diagnosis was retroperitoneal tumour.
      Surgical exploration revealed a totally resectable retroperitoneal tumour with a
      histological diagnosis of ganglioneuroma.

PMID- 9559072
TI  - [The treatment of prune-belly syndrome at the University Hospital Center at
      Abidjan (Treichville)].
AB  - Over the past 10 years, we have seen sixteen children (15 males and 1 female)
      with the prune-belly syndrome. We have managed 12 of these children, but 4 of
      them were never reviewed. Abdominal wall reconstruction was performed in 11
      children by dissection of spermatic vessels and fixing the testis in the scrotum.
      Because of our conservative approach to the management of urinary tract
      dilatation, we performed only one nephrostomy and 3 unilateral nephro
      ureterectomies. Seven children were reviewed. The result of abdominal wall
      reconstruction was good in terms of cosmetic appearance and psychologic effect
      for the parents; we have observed no atrophic testes after orchidopexy. One of
      these children suffers from chronic renal failure, while the other children have
      good renal function. Prune-belly syndrome is a disease with a broad spectrum. The
      prognosis depends on the degree of renal dysplasia. These children require long
      term follow-up.

PMID- 9559073
TI  - [Appendiceal mucocele disclosed by a psoas tumor. Apropos of a case].
AB  - Mucocele of the appendix is a rare lesion. Rupture of appendicular mucocele into
      the psoas is uncommon. We report a case of a 77-year-old man, with psoas tumor on
      abdominopelvic ultrasonography and computed tomography. The preoperative
      diagnosis was type III hydatid cyst of the psoas, psoas tumor or retroperitoneal
      mass. Surgical exploration revealed an appendicular mucocele ruptured into the
      psoas. Appendicectomy was performed with an uneventful postoperative course after
      3 years. The authors discuss the diagnostic and therapeutic problems raised by
      this rare lesion.

PMID- 9559074
TI  - [Rigid ureteroscopy. Apropos of 88 cases].
AB  - Rigid ureteroscopy has become a common tool for the diagnosis and management of
      several diseases of the upper urinary tract. Between April 1990 and April 1996,
      92 ureteroscopy procedures were performed in 88 patients in the B Urology
      Department of Avicennes hospital for diagnostic or therapeutic purposes. The
      commonest therapeutic procedure was stone manipulation (72 cases). The overall
      success rate was 90.8% (Distal ureter: 89.6%, mid ureter: 80%, lumbar ureter:
      100%) and the complication rate was 4%. Therapeutic ureteroscopy was also used to
      dry ureterovaginal fistula (4 cases) and ureteral fistula with retroperitoneal
      urinoma (2 cases), and to remove a double J stent which had migrated into the
      pelvic ureter (3 cases). Diagnostic ureteroscopy was performed for 7 ureteral
      strictures including 3 extrinsic compressions and 4 ureteral strictures all
      treated with dilatations after biopsy. One false passage was observed among
      diagnostic ureteroscopy procedures. Rigid ureteroscopy is a minimally invasive
      and reliable technique for the management of ureteric calculi and for the
      diagnosis and treatment of other ureteric lesions.

PMID- 9559076
TI  - [Primary urothelial carcinoma of the urethra. Apropos of a case].
AB  - We report an unusual case of primary transitional cell carcinoma in the bulbar
      urethra. The patient was a 52-year-old man with a history of sexually transmitted
      disease. The clinical presentation was bladder retention with urethral bleeding.
      Radiological examination and cystoscopy showed a bulbar urethral tumor. The
      pathological diagnosis was Grade III transitional cell carcinoma with invasion of
      the corpus spongiosum (T2). Partial resection of the urethra was performed and
      the patient has been without evidence of disease for two years.

PMID- 9559075
TI  - [ST52 treatment of cancer of the prostate during the hormonal resistance phase].
AB  - OBJECTIVE: Stilboestrol phosphate (ST 52) was evaluated on pain, general status,
      life expectancy and PSA, in a retrospective study of patients with prostatic
      carcinoma and relapse to hormonal treatment. MATERIAL AND METHODS: 32 patients
      were treated by infusion of Stilboestrol phosphate at a daily escalating dose
      from 1.2 to 3 g over a period of 10 days, then subsequently oral administration.
      RESULTS: Minor complications, especially nausea were observed in 12 cases but no
      major complication or interruption of treatment. Improvement for pain alone or
      with general status was obtained in 50% (16 cases) at 3 months, but at one year
      only 10% were still improved. Median survival was 8 months, with 19.4 months for
      responders at the end of infusions and 4.2 months for non-responders
      respectively. CONCLUSION: Stilboestrol phosphate can obtain a clinical response
      with low morbidity when relapse to hormonal treatment occurs. Infusion responders
      have a better life expectancy.

PMID- 9559077
TI  - [Torsion of an undescended testis. Apropos of a case].
AB  - The authors report an uncommon case of torsion of an inguinal undescended testis
      occurring in a 15-year-old child. He consulted seven days later for isolated left
      inguinal pain. Physical examination showed a left inguinal mass, and only the
      right testis was palpable within the scrotum. Sonography revealed left inguinal
      mass with echogenic and heterogeneous contents in keeping with undescended
      testis. The diagnoses of testis tumor or testis torsion were suggested. Surgical
      exploration revealed a mass suggesting a testis tumor. Orchidectomy was
      performed. Histological examination showed that the mass corresponded to a
      necrotic ischemic testis without tumor cells. In the light of this case, the
      authors analyse the diagnostic aspects and management of torsion of an
      undescended testis.

PMID- 9559078
TI  - Learning to talk about it.

PMID- 9559079
TI  - Risk factors as determinants of dental neglect in children.
AB  - Although neglect represents over a half of both reported and substantiated cases
      of child maltreatment each year, it is misunderstood and under-reported. Dental
      neglect, a form of physical neglect, is ignored to an even greater degree.
      Certain families appear to be more at risk for neglect, in some form, than
      others. Predisposing risk factors that may increase the incidence of neglect
      include characteristics of parents and children, family situations, socioeconomic
      and demographic circumstances, and parental beliefs and practices. Dentists,
      particularly pediatric dentists, are in unique positions to evaluate not only the
      dental needs of children, but also family situations and circumstances that might
      affect their dental well-being. Knowledge and understanding of the various risk
      factors discussed will enable dentists to address the problem of dental neglect
      from a preventive approach, rather than strictly treating is results. Further
      research is needed to develop effective methods for both the evaluation and, if
      necessary, the education of at-risk individuals on the importance of good oral
      hygiene and professional care.

PMID- 9559080
TI  - Child abuse and neglect: assessment of dental students' attitudes and knowledge.
AB  - Although many North American dental schools have increased their curriculum hours
      dedicated to the issue of child maltreatment, the majority of schools still
      allocate only one to two clock hours for this subject. The purpose of this study
      was to evaluate the self-perceived knowledge of and attitude toward child abuse
      and neglect, of undergraduate dental students at the University of Texas Dental
      Branch at Houston, as well as the effectiveness of the various educational
      methods used in the instruction of this material. Students in general, recognized
      a need for improvement of both the quality and quantity of this aspect of their
      undergraduate curriculum. The results indicate, however, that the child
      maltreatment curriculum at this institution had minimal effect on the acquisition
      and retention of information related to this subject. Dental educators have the
      responsibility to see that their students are competent, not only in the
      technical aspects of dentistry, but in their social responsibilities, as well.
      The ability to recognize suspected cases of child maltreatment is such a
      responsibility.

PMID- 9559081
TI  - Severe bone loss caused by orthodontic rubber bands; management and nine-year
      follow-up: report of case.
AB  - This case reports the early diagnosis and treatment of an iatrogenic acute
      localized periodontitis arising from the incorrect use of orthodontic elastic
      rubber bands to close a maxillary midline diastema in an eight-year-old girl. The
      case illustrates the misdiagnosis and mismanagement of a transitional diastema in
      the "ugly duckling" stage of the mixed dentition. The nine-year follow-up shows
      that thorough periodontal and orthodontic management has allowed successful
      retention of both maxillary permanent central incisors, which had initially
      pathological grade 3 vertical mobility, little remaining alveolar bone, and a
      hopeless prognosis.

PMID- 9559082
TI  - A comparison of the bond strength to enamel and dentin of two compomers: an in
      vitro study.
AB  - The aim of this study was to evaluate the bond strength of two resin-reinforced
      glass ionomer cements to etched and unetched enamel and to dentin. Thirty-six
      noncarious human premolar teeth were used. Flat buccal and lingual surfaces were
      prepared. Dyract and Compoglass were used. The teeth were distributed at random
      into six groups of six teeth each. The materials were handled according to
      manufacturers' instructions. In groups 1 and 3 the enamel was etched with 37
      percent phosphoric acid. All samples were sheared with an Autograph AG5 machine
      at a crosshead speed of 0.5 mm/min. Two way ANOVA and comparison with the Tukey
      test were used to evaluate the results. These showed that on etched enamel Dyract
      had a significantly higher bond strength (p = 0.02); on unetched enamel
      Compoglass had a statistically higher bond strength (p = 0.003), and on dentin
      the materials provided the same bond strength. Overall, disregarding surfaces,
      there was no difference between the two materials.

PMID- 9559084
TI  - Preeruptive intracoronal radiolucencies: review and report of case.
AB  - Intracoronal radiolucencies in unerupted teeth are an uncommon radiographic
      finding; but their early detection and classification allow the most appropriate
      management protocol to be developed. Early separation of lesions into those that
      are developmental and remain static and those that are reactive and aggressive is
      necessary for a controlled outcome. The current paper reviews possible formative
      mechanisms and describes a case of severe intracoronal resorption resulting in
      loss of the tooth.

PMID- 9559083
TI  - A retrospective radiographic survey of embedded primary molar roots in Saudi
      adult patients.
AB  - This retrospective study reports the radiographic prevalence of embedded primary
      molar roots within Saudi adult dentulous patients. Embedded roots of primary
      molars were viewed radiographically by evaluation of the records of 300 patients.
      Embedded primary molar roots were detected in 7 percent of the viewed patient
      radiographs. Fifty-five percent of the embedded roots demonstrated the
      concomitant existence of partial bony ankylosis. The remaining 45 percent of the
      embedded roots were surrounded by an intact lamina dura and periodontal ligament
      space. The frequency of occurrence demonstrated an age-based relationship,
      showing 9 percent prevalence in the older age-group (41-50 yr.) as compared to a
      45 percent occurrence seen in the younger (15-20 yr.) group. Seventy-seven
      percent of the embedded roots were found within the mandible as compared with a
      23 percent occurrence in the maxilla.

PMID- 9559085
TI  - Early treatment of posterior and anterior crossbite in a child with bilaterally
      constricted maxilla: report of case.
AB  - A case report of a young patient with anterior and bilateral posterior crossbite
      was presented. She was severely brachyfacial with a mild Class III malocclusion
      due to slight maxillary retrusion. Early orthodontic therapy using a simple,
      removable, maxillary expansion appliance provided the patient with a stable,
      functional occlusion and good esthetics.

PMID- 9559086
TI  - Infraclusion of primary molars: reports of cases.
AB  - A review of twenty-five patients (nine boys and sixteen girls with a mean age of
      13.6 years) with infraclusion of primary molars is reported. There were thirty
      two infracluded teeth, twenty-one (65.6 percent) maxillary primary molars and
      eleven (34.4 percent) mandibular primary molars. The primary first molar was
      found to be in infraclusion in four (12.5 percent) cases and the primary second
      molar in twenty-eight (87.5 percent) cases. Submergence was mild in fifteen
      cases, moderate in five, and severe in twelve. The permanent successor was
      lacking in four (12.5 percent) infracluded teeth. Aplasia of a nonsuccedaneous
      tooth was observed in four patients (more than one aplasia in three of them).
      Sixty-five percent of the teeth distal to the infracluded tooth had some degree
      of mesioversion, and 34.4 percent showed a distoversion of the mesial tooth.
      Twenty-one patients underwent orthodontic therapy because of malocclusion induced
      by the submerged tooth or for other reasons. A total of twenty-five (78.1
      percent) teeth had to be extracted (surgical extraction in seventeen cases). An
      alveolotomy made to help the succedaneous tooth to erupt was necessary in ten
      cases.

PMID- 9559087
TI  - Is your next young patient pre-anorexic or pre-bulimic?
AB  - Eating disorders often have their roots in the preteen years. Pediatric dentists
      may provide the initial warning for the care of these youngsters. An introduction
      is provided to the demographics, diagnosis, and treatment of anorexic and bulimic
      young females (primarily) and males.

PMID- 9559088
TI  - Profile of primary teeth with pulpal involvement secondary to caries.
AB  - The objective of this retrospective study was to determine the profile of primary
      teeth with pulpal involvement secondary to caries that required pulp therapy or
      extractions. Three hundred and ninety teeth were selected in 215 children (twelve
      years old and under) at an inner-city clinic in the United States over an
      eighteen-month period. An analysis of frequency distribution was done. Molar
      teeth were most affected by this stage of caries with morbidity increasing with
      age. In the under-six-year-olds, however, maxillary incisors were most affected.
      Extraction was the predominant treatment selected for the incisors with this
      degree of caries. Pulp therapy was the treatment of choice for molar teeth in the
      under-six-year-olds, but this trend was reversed with the number of extractions
      increasing in the six-to-twelve-year-old children.

PMID- 9559089
TI  - Sexually transmitted diseases and children: there is good news, but....
AB  - A review is provided of a series of federal agency reports on sexually
      transmitted diseases among children and young adults. While there have been
      marked decreases in the number of reports of disease, continued infection of
      youngsters less than fifteen years of age is a continuing reality.

PMID- 9559091
TI  - Temporal variation of allozyme frequencies in Aedes albifasciatus (Diptera:
      Culicidae) from Argentina.
AB  - Aedes albifasciatus is a floodwater mosquito widely distributed in Argentina. It
      is important from economic and medical points of view. A 4-year survey of
      seasonal variation in allele frequencies in a population of this species was
      undertaken to determine possible changes in the genetic structure and their
      correlation with environmental conditions. Significant temporal variation was
      detected at most of the loci, but it did not follow a cyclic or seasonal pattern.
      Multivariate analysis of principal components showed a remarkable homogeneity of
      samples collected from December 1993 to April 1995 and a clear differentiation of
      the November 1991, March 1992, and November 1993 samples. This variation could be
      correlated with the magnitude of rainfall occurring in the area. Passive
      transport of larvae by water streams and river freshets produced by floods would
      have mixed larvae from breeding sites with different allele frequencies, causing
      the genetic differentiation observed.

PMID- 9559090
TI  - Dental caries prevalence and dental health care of Mexican-American workers'
      children.
AB  - The purpose of this study was to determine the prevalence of dental caries and
      the use of dental services in a pediatric population of Mexican-American migrant
      workers. The results were compared with the Mexican-American child population
      from the Hispanic Health and Nutrition Examination Survey (HHANES). One hundred
      thirty three-to-sixteen-year-old children participated in the study. The children
      who were born in Mexico and those who spoke Spanish had seen the dentist less
      often and had a higher incidence of decayed teeth than those who were born in the
      US and than those who spoke English (p < 0.05). The children from low-income
      families had visited the dentist less frequently and did so at an older age than
      those from high income families (p < 0.05). When compared with HHANES, the
      children in this study visited the dentist at an older age, had been to the
      dentist less often, were less likely to have dental insurance, and had a higher
      incidence of dental caries than the children from HHANES (p > 0.05). This study
      demonstrated a general lack of dental health knowledge, a disproportionate
      prevalence of decayed teeth and unmet dental need in the Mexican-American migrant
      workers' children.

PMID- 9559092
TI  - Genetic specificity of stress-induced anemia in rats.
AB  - There is a genetic difference in rat hemoglobin (Hb) beta-chain structure, with
      alternate alleles, A and B, at a single locus. This study was designed to find
      out whether marrow sensitivity due to gamma exposure and experimentally induced
      anemia in age-matched adult rats is entirely strain specific or is a combination
      of both strain and Hb genotype. Eight strains of inbred and outbred rats
      comprising AA and BB types were examined. The data indicate that there is a
      relationship between marrow sensitivity and Hb genotypes in response to
      erythropoietic stress caused by three techniques.

PMID- 9559093
TI  - Comparison of mtDNA variants among Mediterranean and New World introductions of
      the Mediterranean fruit fly Ceratitis capitata (Wied.).
AB  - Restriction enzyme cleavage sites of mitochondrial DNA (mtDNA) from the
      Mediterranean fruit fly (Ceratitis capitata) were found to vary among
      Mediterranean and New World populations. A restriction map for six populations
      (one from Greece and five from the New World) is constructed for the
      Mediterranean fruit fly. Six diagnostic restriction enzymes (EcoRI, EcoRV,
      HaeIII, HindIII, SstI, XbaI) are assigned three geographically distinct main
      types, CI, CII, and CIII.

PMID- 9559095
TI  - Allozyme polymorphism and geographic variation in the small brown planthopper,
      Laodelphax striatellus (Homoptera: Delphacidae).
AB  - The small brown planthopper, Laodelphax striatellus, immigrates annually into
      Japan over the East China Sea from the Asian mainland. It is not known whether
      this long-distance dispersal has any effect on the genetic structure of Japanese
      L. striatellus populations. The dispersal of L. striatellus is suspected to be
      relevant to the population dynamics of infection with the parasitic bacterium
      Wolbachia, which causes cytoplasmic incompatibility in L. striatellus. Wolbachia
      infection has spread within and among Japanese L. striatellus populations due to
      this cytoplasmic incompatibility. In the present study, the geographic
      differences among II L. striatellus populations from Japan and Taiwan was
      investigated using allozyme polymorphism. FST values on three enzyme loci (GPI,
      PGM, and AK) indicated a geographically differentiated population structure.
      Significant differentiation was found even among populations located along the
      course of the long-distance dispersal. The results indicated that long-range
      dispersal of L. striatellus does not occur regularly over the main islands of
      Japan and that it does not have a large effect on the population structure of L.
      striatellus. This conclusion is in agreement with the geographically variable
      life history of L. striatellus adapted to local climates. The short-term rice
      stripe epidemic, which is vectored by L. striatellus, in northwestern Kyushu,
      Japan, during 1985 and 1986 corresponds to these results. Based on the present
      findings, short-distance dispersal was considered to drive the spatial spread of
      Wolbachia infection among L. striatellus populations.

PMID- 9559094
TI  - Genetic variation in some populations of the golden-striped salamander,
      Chioglossa lusitanica (Amphibia: Urodela), in Portugal.
AB  - Genetic variation in the golden-striped salamander (Chioglossa lusitanica) was
      assessed in 231 individuals from four Portuguese populations by means of
      horizontal starch gel electrophoresis and isoelectric focusing. Three of 19
      enzyme systems, representing 21 presumptive loci, were found to be polymorphic:
      phosphoglucomutase 1 (PGM1), peptidase B (PEPB), and peptidase D (PEPD). The
      observed average heterozygosity in Chioglossa lusitanica (0.027) is significantly
      lower than that observed for other amphibians, either urodeles or salamandrids.
      Differences in allele frequencies and the presence of private alleles are
      indicative of a high degree of population differentiation. PEPD, in particular,
      seems to be a diagnostic locus separating the southernmost population studied
      from the others.

PMID- 9559096
TI  - Sequences of exon 6 and the adjacent intron boundaries of the rat platelet
      derived growth factor A-chain gene: implications for alternative splicing.
AB  - Platelet-derived growth factor (PDGF) is a potent stimulator of vascular smooth
      muscle cell growth. Two isoforms of PDGF A-chain mRNA that either include (long
      form) or exclude (short form) exon 6 are produced as a result of alternative
      splicing in mouse, rabbit, and human. The short form of PDGF A-chain is expressed
      in both resting and activated cells, while the long form is present predominantly
      in activated cells. Reverse transcription-polymerase chain reaction analysis with
      primers encompassing exon 6 revealed the presence of both long- and short-form
      PDGF A-chain transcripts in rat vascular smooth muscle cells. The nucleotide
      sequences of exon 6 and its intron boundaries were determined from rat vascular
      smooth muscle cell cDNA and rat leukocyte genomic DNA. Translation of the long
      form of PDGF A-chain mRNA was shown to terminate in the 70-base pair exon 6.
      Conserved sequences that may contribute to the regulation of alternative RNA
      splicing were identified in intron 5.

PMID- 9559097
TI  - Actions of sodium fluoride on acetylcholinesterase activities in rats.
AB  - This study was carried out to observe the effects of sodium fluoride on
      acetylcholinesterase (AChE) activities in the cerebral synaptic membranes (SPM)
      and the peripheral red blood cells (RBC) of rats by in vivo and in vitro
      experiments. In the in vivo study, pregnant rats ingested ad libitum fluorinated
      drinking water (5, 15, 50 ppm F-) during their gestation and lactation. It was
      shown that the AChE activities of the SPM and peripheral RBCs in maternal rats
      exposed 5-50 ppm F- for 60 days were elevated significantly by 30.0-67.6% and
      12.5-31.9% in a dose-dependent manner, respectively. The AChE activities of their
      offspring 80 days after birth were also increased (8.7-28.7% for SPM and 20.6
      32.4% for RBC). In contrast, the AChE activities of SPM in vitro were inhibited
      by 5.0-50.0 mmol F-/L treatment in a time- and dose-dependent manner. Analysis
      with the Hanes plots suggested that the enzymesubstrate kinetics are consistent
      with a mixed type of inhibition.

PMID- 9559098
TI  - Lead induced disorders in hematopoietic and drug metabolizing enzyme system and
      their protection by ascorbic acid supplementation.
AB  - Effect of vitamin C supplementation in restoring lead induced alterations in
      hematopoietic system and drug metabolizing enzymes were investigated in male
      rats. Intraperitoneal administration of 20 mg/kg lead produced a significant
      inhibition of heme synthesis in blood and liver and drug metabolism in liver.
      Toxic insult by lead also resulted into a marked decline in tissue thiols and
      vitamin C levels. Oral supplementation of vitamin C (100 mg/kg for 3 days)
      completely restored blood delta aminolevulinic acid dehydratase, uroporphyrinogen
      I synthetase and a few drug metabolizing enzymes. Level of vitamin C and
      sulfhydryl contents too recovered to a great extent. A marked reduction in blood
      and liver lead concentration occurred on vitamin C supplementation although renal
      lead contents were marginally reduced in lead exposed animals. The results, thus,
      indicate a significant protective action of vitamin C against toxic effects of
      lead on heme synthesis and drug metabolism.

PMID- 9559099
TI  - Hematomas and limb skeletal malformations in chicken embryos following exposure
      to 5-fluoro-2-deoxyuridine.
AB  - Vascular injury or interruption may play a role in vertebrate limb teratogenesis.
      Since 5-fluoro-2'-deoxyuridine (FdU) can cause vascular injury in the murine limb
      and skull prior to the appearance of skeletal malformations in these structures,
      we studied the effects of this chemical on skeletal development in the chick
      embryo and noted any vascular injury. The yolk sacs of day three chick embryos
      (Hamburger and Hamilton states 17-19) were injected with solutions of vary
      concentrations of FdU in saline. The embryos developed until the 10th day of
      incubation when they were fixed for study. Uninjected, saline injected, and sham
      injected control embryos were similarly fixed. Upon gross inspection, frequent
      diffuse and saccular hematomas, as well as fluid-filled blisters, were noted in
      the limbs of embryos treated with FdU. After the embryos were fixed and cleared,
      and the skeletons stained, significant skeletal malformations were observed in
      these limbs. Bony elements of both the upper and lower limbs were affected in at
      least some of the embryos. The combination of FdU-induced hematomas and blisters
      with associated skeletal malformations in the same regions of some embryos
      suggests a relationship between these phenomena.

PMID- 9559100
TI  - Infectious disease surveillance in China.
AB  - A national system of infectious disease surveillance was established in 1959 in
      China. Now it consists of three subunits, namely, national disease reporting
      system (NDRS), nationwide disease surveillance points (DSPs), and surveillance
      network for specific infectious diseases. There are 35 notifiable infectious
      diseases, which are divided into Classes A, B, and C. The functions of the
      surveillance include explaining the natural history of infectious diseases,
      describing the distribution of case occurrence, triggering disease-control
      effort, monitoring epidemic of infectious diseases during natural disasters,
      predicting and controlling epidemics and providing the base of policy adjustment.

PMID- 9559101
TI  - Effects of some thiol chelators on enzymatic activities in blood, liver and
      kidneys of acute arsenic (III) exposed mice.
AB  - The effects of meso 2, 3-dimercaptosuccinic acid (DMSA), sodium 2, 3
      dimercaptopropane 1-sulfonate (DMPS) and S-adenosyl L-methionine (SAM) on the
      enzymatic activities of mice were studied. The mice were given intraperitoneal
      (i.p.) injections of these chelating agents (1 mmol/kg) and 3 h later the
      activity of delta-aminolevulinic acid dehydratase (ALAD) in the blood, and
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma
      glutamyltranspeptidase (gamma-GT), alkaline phosphatase (ALP) in the liver and
      kidney were determined. The activity of blood ALAD was significantly increased by
      the administration of DMSA and SAM while DMPS had only a moderate effect. The
      activities of other hepatic enzymes changed little when the mice were treated
      with these chelating agents, except for a significant reduction in hepatic ALP
      activity following DMPS administration. Arsenic (III) administration markedly
      increased the activities of ALT and ALP in the liver and kidneys. The changes in
      the enzymatic activities by treatment with arsenic were prevented by injection of
      DMSA, DMPS and SAM, DMSA being the most effective. These results indicate that
      DMSA, DMPS and SAM were not toxic to the liver or kidneys of mice and that
      treatment with DMSA is more effective than DMPS or SAM in protecting mice from
      acute hepatic or renal toxicity caused by arsenic.

PMID- 9559102
TI  - A new concept in the control of iron deficiency: community-based preventive
      supplementation of at-risk groups by the weekly intake of iron supplements.
AB  - Iron deficiency (ID), defined as an insufficient supply of iron to the cells of
      the body after iron reserves have been exhausted, is the most prevalent single
      nutritional deficiency, affecting over 2,000 million people, mostly in the
      developing world. Infants, small children, adolescents and pregnant and fertile
      age women are most vulnerable. Only about 50% of people with ID develop iron
      deficiency anemia (IDA), since this is a late manifestation of chronic ID. Based
      on the average daily iron requirement and on the rate of iron reutilization from
      red cell hemoglobin destruction, it can be estimated that after iron stores have
      been depleted, it takes about 4 months of ID erythropoiesis for adult women to
      have a drop in hemoglobin concentration [Hb] of 10 g/l, if the iron intake is
      only 70% of requirement. IDA can be defined by a [Hb] below an appropriate cut
      off point for age, sex, physiological condition and altitude above sea level, or
      by a [Hb] increment of more than 10 g/l to the administration of adequate doses
      of iron. More than 85% of the nutritional anemias are IDA alone, or of iron
      combined with folate or other nutrient deficiencies.

PMID- 9559103
TI  - Developmental lead exposure alters the distribution of protein kinase C activity
      in the rat hippocampus.
AB  - Chronic low-level lead (Pb) exposure in children is known to cause a deficit in
      learning and memory. In vitro studies have demonstrated that Pb altered protein
      kinase C (PKC) activity. Especially, hippocampal PKC has been correlated with
      performance in several learning tasks. The effects of Pb exposure on hippocampal
      PKC were investigated during development at various postnatal ages: postnatal day
      (PN) 7, 14, 28, and 56. Two-tenth % Pb acetate was administered to pregnant and
      lactating dams and then administered to weanling rats in drinking water. PKC
      activity was measured in both membrane and cytosolic fractions from the
      hippocampi of the controls and Pb-exposed animals. Pb-induced increase in PKC
      activity in the cytosolic fraction was observed in the PN56 rats. In contrast,
      PKC activity was decreased by Pb at PN7 in the membrane fraction. Furthermore, a
      significant decrease in the ratio of membrane to cytosolic PKC activity which is
      representative of PKC distribution was observed in the PN28 and PN56 Pb-exposed
      rats relative to the same-age controls. This study indicates that chronic Pb
      exposure during development influences hippocampal PKC activity and distribution.
      These changes may be involved in the subclinical neurotoxicity of chronic Pb
      exposure in young children.

PMID- 9559104
TI  - Hematological parameters in Bufo arenarum injected with sublethal dose of lead
      acetate.
AB  - Lead has been recognized as a high risk toxic for most organisms including human.
      The effects of Pb in non-mammalian vertebrates are poorly known, particularly in
      anuran amphibians. The purpose of this study was to determine the effect of this
      metal on some hematological parameters of adult Bufo arenarum. It was found that
      all parameters remained unaltered within normal ranges, with the exception of
      reticulocyte counts which was significantly increased compared to the in controls
      (3.7% vs. 0.2%). It is suggested that the selective change found in reticulocyte
      count might be considered as an early response of a biomarker to sublethal
      exposition of Bufo arenarum to lead.

PMID- 9559105
TI  - Comparative study on 4 EIA kits for screening antibody to hepatitis C virus in
      pooled sera.
AB  - Four enzyme immunoassay (EIA) test kits, 1 Canadian product and 3 Chinese
      products, were used in the comparative study. Each pool consisted of 5 sera, and
      the 5 single sera were tested as controls. The tests were carried out according
      to the instructions, keeping the same dilution of each serum in single and pool
      samples. It was found that with the Canadian kit, the positive and negative
      results of pooled sera had no difference from that of the controls (P > 0.10). In
      the case of Chinese Yali and Kehua kits, the positive results of pooled sera
      showed no difference from the controls (P > 0.10), but the optical density (OD)
      of negative pools were increased (P < 0.01), though quite distant from the cut
      off values. In the case of Changzheng kit, the OD of positive pools were
      significantly lower than those of the controls (P < 0.05), and weak positive
      samples missed the detection. However this problem could be overcome by blocking
      the microwells beforehand. Our experiment demonstrate that not all EIA test kits
      are suitable for screening pools for antibody to hepatitis C virus, and that it
      is important to assess the sensitivity of the EIA kit to be used for this
      purpose.

PMID- 9559106
TI  - Inhibition of the specific 3H-DL-Glu binding in the hippocampus of rat brain by
      lead.
AB  - The effect of Pb2+ on 3H-DL-Glutamate (3H-DL-Glu) binding in the membrane
      preparations from the hippocampus of rat brain was investigated with a view to
      explaining the cognitive and learning deficits produced by the heavy metal. The
      results indicated that Pb2+ (3.1-25.0 mumol.L-1) inhibited 3H-DL-Glu binding in a
      concentration-dependent manner. Scatchard analysis further revealed that at a
      concentration of 6.3 mumol.L-1 Pb2+ interfered with binding mainly through
      significantly decreasing the density of binding sites. This finding provided an
      important insight into Pb2(+)-induced impairments in learning and memory
      previously documented in children and in experimental animals chronically exposed
      to Pb2+.

PMID- 9559107
TI  - Detection of cytogenetic effects in peripheral lymphocytes of students exposed to
      formaldehyde with cytokinesis-blocked micronucleus assay.
AB  - Cytokinesis-blocked micronucleus assay was applied as a biological dosimeter to
      detect abnormalities in human peripheral lymphocytes of thirteen students exposed
      to formaldehyde (FA) during a 12-week (10 h per week) anatomy class. Breathing
      zone air samples collected during dissection procedures showed a mean
      concentration of 2.37 ppm (3.17 mg/m3). Ten students from the same school but
      without FA exposure served as controls. Chromosome aberrations (CA) and sister
      chromatid exchanges (SCE) were detected in both groups. The micronuclei (MN) rate
      (6.38 +/- 2.50 /1000) and CA rate (5.92 +/- 2.40%) in the FA-exposed group showed
      a significant increase (P < 0.01) when compared with those of the controls (3.15
      +/- 1.46 /1000 and 3.40 +/- 1.57% respectively). A correlation between MN and CA
      in individuals was observed. SCE in the exposed group were also increased (P <
      0.05), but not so greatly as MN or CA. The results indicated that FA might damage
      the chromosomes of human lymphocytes.

PMID- 9559108
TI  - Informatics: transforming raw data into real medical information.

PMID- 9559109
TI  - A PC-based workstation for real-time acquisition, processing, and display of
      electromyogram signals.
AB  - A system for real-time acquisition, processing, display, and logging of multiple
      channels of the EMG waveform has been described. By designing this system around
      the configuration of a standard PC, custom hardware was avoided. Similarly,
      software was designed in a higher-level language (C), simplifying the programming
      burden and minimizing custom software development. Components of the software are
      available off the shelf. The computational capacity of generic PCs facilitates
      very high rates of numeric calculation, as required by some advanced EMG
      amplitude estimation algorithms. Computational capacity is expected to increase,
      facilitating ever more numerically intensive EMG algorithms that are likely to be
      developed in the future. The system described here has been used in the
      development of an adaptive window EMG amplitude-estimation algorithm. The system
      is extensible and can be altered for many uses related to EMG and biosignal
      processing.

PMID- 9559110
TI  - Validating medical equipment repair and maintenance metrics, Part II: Results of
      the 1997 survey.

PMID- 9559111
TI  - A new approach to acoustical evaluation of human respiratory sounds.
AB  - The authors developed a method for more precise detection and analysis of the
      physical features of respiratory and voice sound transmission to the chest wall.
      Based on their findings using this method, they designed several devices for
      acoustic examination and evaluation of components of human respiratory sounds.
      These devices analyze forced expiratory sounds, distinguish between air-borne and
      structure-borne sounds, and distinguish abnormalities in voice transmission to
      the chest wall. Tests of the devices on human subjects confirmed the validity of
      the authors' theoretical models, which offer promise for the development of a new
      class of medical diagnostic instruments.

PMID- 9559113
TI  - Skin-temperature distribution under a new type of defibrillating electrode.
AB  - The temperature rises under a new type of x-ray-transparent, improved current
      density-distribution defibrillation electrode applied to pig skin were measured
      at four sites with fiberoptic thermal probes. Three anesthetized pigs, ranging in
      weight from 79 to 92 lb, were used. Temperature-time curves were obtained and the
      maximum temperature was identified. For 17 measurements at each site, the maximum
      temperature rise for a 360-joule shock was 317.3 +/- 53.0 millidegrees Celsius.

PMID- 9559112
TI  - An electronic circuit simulating T-type calcium-channel current from the
      sinoatrial node.
AB  - A circuit that simulates T-type calcium-channel current characteristics of the
      sinoatrial (SA) node was developed from discrete electronic components and tested
      at physiologic membrane voltage ranges. The circuit design was based on the T
      type calcium-channel current dynamics obtained from a mathematical model of the
      SA node membrane, which, in turn, is based on physiologic data. The design was
      held at a resting membrane potential and then stepped to new voltages over the
      entire operating range of the T-type calcium channel. The circuit was validated
      by comparing its transient response current with the predicted current from the
      mathematical model. In addition, the peak currents of the circuit were compared
      with plots of peak current obtained from the mathematical model and physiologic
      data. By showing that the electronic circuit mimics the T-type calcium-channel
      current dynamics found within the SA node, the results may provide a foundation
      for developing a novel cardiac pacemaker that is based on the ion-channel
      characteristics of excitable tissue.

PMID- 9559114
TI  - Bioimpedance measurements.

PMID- 9559116
TI  - Human factors usability test and evaluation.

PMID- 9559115
TI  - The clinical engineer: a ghost hunter or manager of EMI.
AB  - The management of EMI and risk control in the clinical environment presents the
      clinical engineer with new challenges and responsibilities. The keys to
      successfully meeting these challenges and responsibilities are education,
      cooperation, and the ability to be creative in the quest for solutions to
      problems of ever-increasing complexity. Experience in detecting and analyzing
      test results, which is gained over time, enhances the skills that clinical
      engineering professionals bring to this challenge. Attention to EMI risks has
      been influenced by a number of factors, including a spirit of cooperation between
      manufacturers and users, concerns over patient care and perceived product
      efficacy, and an increasing number of regulations by European and U.S. regulatory
      agencies. As a result, device emissions are being reduced and device immunity to
      EMI is improving. Further improvements in device immunity are still needed. The
      radio spectrum with regard to intentional radiators is in a continual state of
      flux. As industry attempts to improve labor efficiency through the use of radio
      communications, new and higher-powered sources of RF--both internal and external
      to the physical plant--appear each day in the clinical environment. Since the
      distance between intentional radiators and potentially susceptible devices is
      usually beyond the control of an institution, industry must continue to reduce
      device susceptibility. There should be a stronger dialogue between institutions
      (even if they do not have proactive EMI reduction programs) and manufacturers to
      identify ways to improve device immunity to EMI and to increase product
      designers' and users' awareness of potential problems.

PMID- 9559117
TI  - [Immunologic aspects of cellular therapy].

PMID- 9559118
TI  - [Effect of hemorrhagic shock on learning processes in late posthemorrhagic
      period].

PMID- 9559119
TI  - [Modification with corticosteroids of behavioral effects of corticoliberin
      administered into the neostriatum].

PMID- 9559120
TI  - [Urokinase receptors in human monocytes during angina].

PMID- 9559121
TI  - [Effect of serotonin antibodies on the functional activity of T-, B-lymphocytes,
      and peritoneal macrophages].

PMID- 9559122
TI  - [The role of saliva in supplying of esophageal and gastric mucosa with
      catecholamines in rats].

PMID- 9559123
TI  - [Modifying effect of hypokinesia on reparation regeneration of the liver].

PMID- 9559124
TI  - [Generation of 5alpha-androstan-3beta,17beta-diol in the rat hypophysis].

PMID- 9559126
TI  - [Characteristics of effect of fibrinolysis system on ADP- and serotonin-dependent
      human thrombocyte aggregation].

PMID- 9559125
TI  - [Comparative analysis of neurotropic activity exorphins--derivatives of dietary
      proteins].

PMID- 9559127
TI  - [Receptor mechanism of the neuroprotective effect of GABAergic agents].

PMID- 9559128
TI  - [Steroid hormones--modulators of the lipid composition of lysosomal membranes of
      skin fibroblasts].

PMID- 9559130
TI  - [Study of the restorative effect of various pharmacologic preparations during
      acute sublethal thermal stress induced by microwaves].

PMID- 9559129
TI  - [Effect of subchronic administration of tolcapone on release of striatum dopamine
      and its metabolites induced by L-DOPA and carbidopa].

PMID- 9559131
TI  - [Comparative analysis of effects of adapromine, midantan, and bromantane on the
      bioelectric activity of the rat brain].

PMID- 9559132
TI  - [Effect of nicotinamide on development of experimental allergic
      encephalomyelitis].

PMID- 9559133
TI  - [Effect of various lipopolysaccharides of gram-negative bacteria on the
      macrophage activity, oxidative metabolism, and liver microsomal activity].

PMID- 9559134
TI  - [Changes in alpha-B-crystalline in heart transplants].

PMID- 9559135
TI  - [Effect of duration and number of cell cycles after mutagenic exposure on the
      frequency of sister chromatid exchange].

PMID- 9559136
TI  - [Regulation of expression of human fibroblast interferon gene by human leukocyte
      interferon and cytopathogenic alpha-virus].

PMID- 9559138
TI  - [Effect of biliary stasis on lipid peroxidation and bile composition in in vitro
      experiment].

PMID- 9559137
TI  - [Effect of the novel antineoplastic agent cycloplatam on the structure and
      synthesis of DNA].

PMID- 9559139
TI  - [Effect of administration to mice of cytokines (G-CSF and stem cell factor) on
      hematopoietic progenitor cells mice].

PMID- 9559140
TI  - [Activity of growth hormone-releasing peptide-2 in cultured cells of human
      pituitary adenoma and its interaction with growth hormone-releasing hormone and
      somatostatin].

PMID- 9559141
TI  - [Characteristics of development of oxidative stress in blood plasma of patients
      with familial hypercholesterolemia].

PMID- 9559142
TI  - [Suppressor activity of bone marrow cells in patients with stomach neoplasms.
      Effect of prostaglandins, growth transforming factor-beta, and nitric oxide].

PMID- 9559143
TI  - [Effect of morphine and antipain on synthesis of RNA in neurons and hepatocytes
      of WAG and F344 rats].

PMID- 9559144
TI  - [Effect of chalone and antichalone on free radical processes in the rat liver].

PMID- 9559145
TI  - [Study of blood ultrastructure in pathological pregnancy].

PMID- 9559146
TI  - [Morphologic evaluation of growth ability of central axons in the peripheral
      nerve].

PMID- 9559147
TI  - [Morphologic evaluation of occlusion of arteries by hydrogel with enhanced
      hemostatic effect].

PMID- 9559148
TI  - [Incidence of cancer in Mauritius in 1989-1993].
AB  - Systematic registration of cases of cancer was introduced in Mauritius as of
      1989. This article analyzes the data concerning the incidence and mortality of
      the disease from 1989 to 1993. At the end of each year, the archives of the
      Central Laboratory of Hospitals, the admissions register at the only center for
      radiotherapy, the discharge resumes of patients classified as suffering from
      cancer of all the regional hospitals and the archives of the Medical Assistance
      Service regarding treatment abroad were examined and information drawn from them
      in order to fill out the information form of the cancer register (10 items per
      case). For the period studied, 4293 new cases of cancer were detected of which
      1784 (41.6%) among men. The main organs affected were, for men: the lungs (12%),
      the mouth/pharynx (10%), and the stomach (8%); for women: the breast (24%), the
      cervix (21%), and the ovaries (6%). The incidence of cancer has increased at an
      annual average of 8% for both sexes, reaching in 1993 the standard (world)
      incidence of respectively 106 and 122 cases per 100,000. Over the same period,
      cancer rose to 2nd to 3rd place in causes of death, accounting for approximately
      8 to 9% of deaths. The ratio of mortality/incidence is 0.85 among men and 0.58
      among women. The distribution of cancer according to age, location and ethnic
      group points to interesting and significant results which can be subsequently
      compared to that of other countries in the region. The second phase of
      registering cancer in Mauritius is presently being undertaken.

PMID- 9559149
TI  - [Registry of cancer in Reunion: data of the first five years of registration
      (1988-1992)].
AB  - After explaining the purposes of a general cancer register in Reunion Island and
      describing objectives and running, main results from 1988 to 1992 are introduced.
      Comparison with EUROCIM network shows that cancer standardized incidence (all
      sites) in Reunion Island is at the same level as in Martinique and lower than in
      other registers. Nevertheless some cancers are particularly frequent. For men, as
      for most European registers, lung cancer (15%) is the most frequent diagnosed
      cancer, followed by esophagus and stomach cancers. Reunion Island belongs to
      areas with highest incidence rates for esophagus cancer. Breast cancer (21%),
      despite a lower incidence than in Europe, is still the first female cancer,
      followed by cervix cancer (18%) which incidence, as in Martinique, is very high.
      We don't notice high discrepancies between mortality rates and incidence rates in
      Reunion Island during that period.

PMID- 9559150
TI  - [Cancer in Madagascar. Experience of the Institut Pasteur de Madagascar from
      September 1992 to June 1996].
AB  - The Unit of the anatomo-pathology in the "Institut Pasteur de Madagascar" (IPM)
      examined in the period from September 1992 to June 1996 tissue specimens from
      10,275 patients. Tumorous pathology presented 40% of the tissues and half of
      which were of malign etiology. 64% of the cancer diagnosed were in females.
      Cervical cancer was most frequently observed (17%), followed by breast cancer
      (16%). Cancer in the gastro-intestinal tract (15%) was most often located in the
      colon without sex difference. Stomach cancer occurring predominantly in males
      presented 25% of the total cases of cancer in the gastro-intestinal tract. Cancer
      of liver is rarely diagnosed despite the high prevalence of infection with
      hepatitis B virus. Skin cancer constituted 9% of the malign diagnosis and was
      mainly found in males. Children under 15 years old presented 7.4% of the total
      cases of malignancy with the haematopoietic tissues (30%) and the eyes (17%) as
      the most frequent topic locations. Due to a very low seroprevalence of the HIV in
      Madagascar, malign tumours associated to AIDS were only seen in a few rare cases.
      The review of cancer cases in the IPM may not be representative for the cancer
      epidemiology of Madagascar because of a general very low level of health care
      coverage, especially in the rural areas. Furthermore, a major part of the
      specimens originates from easily accessible organsystems, whereas other organs
      seem less investigated due to lack of appropriate available technique. Therefore,
      it is not feasible for the moment to establish a cancer register in Madagascar,
      although the Unit of Pathology in the IPM can offer a valid cancer diagnostical
      service.

PMID- 9559151
TI  - [Prevalence of thyroid cancer in Reunion from scintigraphic data].
AB  - This work is a retrospective two years study of thyroid cancer, diagnosed in
      Reunion Island, using scintigraphic cold regions. Between April 1993 and April
      1995, 1,364 thyroid scintigraphic studies were performed in the CHD F. Guyon at
      Saint Denis, Reunion). These studies resulted from all types of indication and of
      them 691 had cold regions, with 22 thyroid cancers among them, (i.e. a prevalence
      of 3.20% of cold areas). Analysis of these cancers allowed recognition of various
      characteristics. A large majority (82%) were in females, whose median age at the
      time of diagnosis was 49 years (as opposed to 48 years for the male patients).
      The associated cold zones were usually isolated cold nodules. Anatomical
      pathology investigation indicated six were papillary, five mixed, three vesicular
      nodule, four microcarcinoma, one each of anaplastic, one follicullar thyroid
      carcinoma, and two were metastases. Their geographical distribution was
      superposed on their medical demography. Treatment was surgical, but a variety of
      procedures was used. Generally the diagnostical, therapeutical and follow up
      procedures were not standardised. Needle cell biopsy was virtually excluded from
      the decision-making trees and a variety of protocols was used. In addition there
      are no local epidemiological data available concerning thyroid cancers. An
      improved method for dealing with these cancers appears to be essential for
      Reunion. It must be associated with a greater awareness from medical
      practitioners, agreement on procedures for diagnosis, treatment and follow up and
      the setting up of a register for thyroid cancer in the "Department". Some thought
      before detailed involvement should be given to the setting up of a team, trained
      in needle cell biopsy, and an associated metabolic radiotherapy facility, so
      allowing appropriate procedures and follow up for thyroid cancers in this
      "Department".

PMID- 9559154
TI  - [Genomic subtypes of hepatitis C virus: epidemiology, diagnosis and clinical
      consequences].
AB  - Hepatitis C virus demonstrates a high degree of variability HCV isolates have
      been classified into at least six genotypes, according to the percentage of
      nucleotide sequence homology. Geographical differences in the distribution of
      virus genotypes are well documented. Types 1, 2 and 3 are the major types
      observed in Japan, Western Europe and North America; type 4 has been found in
      Central and Northern Africa and in the Middle East; type 5 has been described in
      South Africa, type 6 in South-East Asia. The relative prevalence of these
      genotypes varies between different regions. In the Indian subcontinent, subtype
      1b seems to be the most prevalent type, but many isolates have been described,
      related to genotype 3, in Northern and Southern India, Pakistan and Nepal. HCV
      genotypes may have potential clinical implications: a) the association with the
      severity of liver disease is still controversial; b) the association between some
      genotypes, particularly 1b, and a poor response to interferon alpha therapy has
      been well established; c) genotyping may be useful for identifying some unusual
      modes of transmission of the virus. Finally, the variability of HCV virus has
      major implications for the design of new vaccines strategies since there is no
      cross-protection between different HCV types.

PMID- 9559155
TI  - [Hepatitis G virus: a new agent responsible for viral hepatitis].
AB  - Modern biology has allowed to detect a new hepatitis virus called G (HGV),
      joining an already important member of hepatitis viruses. Thus the share of viral
      hepatitis non A-non D decreases. The HGV belongs to the Flaviviridae and is
      similar to the HCV. Transmission occurs essentially by contaminated blood. There
      are still some open questions, particularly concerning the real pathogenic
      responsibility of the virus, which is far from clear considering latest
      publications. Further studies are necessary to precise epidemiologic data, ways
      of transmission, and pathogenic properties.

PMID- 9559156
TI  - [Vaccination against hepatitis B in France in 1996].
AB  - A national campain aimed at promoting immunization against hepatitis B was
      launched in 1994. Two years later, a survey was designed to estimate the
      situation of the hepatitis B vaccination in France. Around ninety per cent of
      physicians were hepatitis B vaccinated. The rate of vaccinated population among
      public hospitals personnel were more than 90% and lower in private hospitals
      (79%). A quarter of the general population was vaccinated and the higher rate
      (69%) was observed in the 13-20 years young people. Progressively the
      contribution of the physicians to the vaccination was increasing (89% in 1996).
      After a selective vaccination of risk groups and the instauration of the
      prevention of mother/infant transmission, the French programme was extended to
      cover adolescents and children. The success of the hepatitis B vaccination
      campain was obtained by the promotion message toward population and physicians.

PMID- 9559162
TI  - [The island of Mauritius: insularity, tropicality, modernity, a dialogue in the
      form of a lesson].
AB  - Mauritius, a lost volcanic island in the indian ocean situated at the 20th degree
      of latitude, is a tiny state which got its independence in 1968. The isolation,
      the tropicality, the demographic boom, the ethnic diversity and the absence of
      raw materials could funnel this peaceful beauty to become a hot-bed of
      desperation and violence. This place which is one of the most densely populated
      areas, is an example of modern democracy and cultural coexistence. Owing to a
      skillful and pragmatic politic, its leaders have transformed handicaps into trump
      cards. The allocation of a part of the GNP for social and hygienic investments
      had been the locomotive pulling the train of improvements and raising the
      standard of living for the inhabitants. The ageing population, the rapidity of
      evolution the demographic and health transitions are expression of this skillful
      politic. In less than twenty years, this island conquered underdevelopment and
      proved that there is no tropical fatality when a programme of health accompanies
      development.

PMID- 9559163
TI  - [Insularity and epidemic risks in Reunion].
AB  - The risks of epidemics in Reunion island depend on determining or favourable
      factors. The determining factors, links in the epidemic chain, may or may not
      exist but they can be introduced from the outside. The risk of importing these
      factors is especially important when the exchanges with the epidemic zones are
      easy and frequent. Reunion island, at the moment exempt from certain pathologies
      such as malaria, dengue-fever and urinary Schistosomiasis, is a good example.
      However, if the presence of these determining factors is necessary, that is not
      enough in itself. Other factors come into play; in particular physical
      (leptospirosis) or socio-economic conditions (cysticercosis, intestinal parasitic
      diseases). The latter play a major role in the hygienic conditions and also in
      the research and prevention which are easier on an island.

PMID- 9559164
TI  - [Dengue, arbovirus and migrations in the Indian Ocean].
AB  - An arbovirus requires a competent haematophagous arthropod for transmission from
      one vertebrate to another susceptible host. Air transportations allow quick
      transfers from place to place and the diffusion of potential vectors or
      infectious hosts. The merchandise transportation by containers allowed the
      diffusion of Ae. albopictus from Asia through Africa and America. Emerging
      arbovirusis may occur in zones where they do not exist. Dengue which originally
      was located in southeastern Asia, is the most important arbovirusis in the world.
      The occurrence of dengue haemorrhagic fever (DHF) in Asia and America, mostly in
      urban areas, increased the global concern about dengue. Likewise, cases of DHF
      are not reported in Africa and in the Indian Ocean southwestern islands. The
      principal vector of dengue, Aedes aegypti, was present during the dengue 1
      outbreak in Comoros, in 1993. In the other islands, only few specimens of Ae.
      aegypti are observed, and described mostly as none anthropophilic forms. The role
      of Ae. albopictus as vector of dengue was suspected and reported during outbreaks
      in Seychelles and Reunion island in 1977-1978. Yellow fever, present in Africa
      mostly in restricted areas, is absent in Asia. Japanese encephalitis considered
      as an emerging disease in India could expand through the islands. Rift valley
      fever, with periodic epizootics in domestic ungulates in Africa, was described as
      a new disease in Madagascar in 1990-1991. Crimean-Congo haemorrhagic fever is
      also present in Madagascar. Humans can be infected by vector bite or by handling
      infectious animal products. The distribution of other viruses (West Nile,
      Sindbis, Wesselsbron or Chikungunya) is discussed.

PMID- 9559165
TI  - [Epidemiological surveillance of grippe and dengue. Reunion, 1996].
AB  - The local Welfare and Health Authorities together with the country council of
      Reunion Island set up a medical supervision network for influenza and dengue
      fever in March 1996. Influenza of which the spreading over the island has never
      been well-researched is anticipated by a vaccination campaign organised in an
      empirical way after a model from the mother country (France). Dengue fever of
      which one of the vectors is omnipresent on the island ranged in an epidemic way
      in 1978. The aim of this network based on watching doctors, the laboratories of
      the island as well as the Pasteur Institute of Madagascar, is to adapt the
      prevention (Flu) and alert the Health Authorities in case of epidemic (Dengue).
      The article shows the results of 1996 observation and touches on the future of
      this type of supervision in a tropical environment.

PMID- 9559166
TI  - [Origin of malaria epidemics on the plateaus of Madagascar and the mountains of
      east and south Africa].
AB  - The Highlands of Madagascar were malaria free until 1878, when a severe epidemic
      occurred, following the development of irrigated rice farming. Then, the disease
      became endemic. Between 1949 and 1962, malaria was "eradicated" on the Highlands
      by joint house spraying and chemoprophylaxis measures. The main vector An.
      funestus disappeared. In 1986-1988, a very severe epidemic with high lethality
      rate devastated the Highlands. It is now under control. Thanks to the data of a
      religious dispensary, we could follow the evolution of malaria on the Highlands
      from 1971 to 1995. The number of cases begin to grow in 1975 when the
      surveillance was neglected. A second step was observed in 1979, when
      chemoprophylaxis/chemotherapy centres were closed. Then, the increase of malaria
      became exponential up to 1988. At the time, the prevalence had became similar to
      that of 1948, before the eradication. The epidemic is not due to global warming
      because the temperature has been stable for the last 30 years. The malaria rise
      was due the cancellation of control measures. When control was reactivated, the
      epidemic ceased. In Swaziland, Zimbabwe and South Africa, malaria epidemics were
      also due to control failure. In Uganda Highlands, above 1500 m, malaria rise
      seems linked to the environmental changes, e.g. the cultures which replace
      papyrus swamp in the valley. But malaria did not overcame the altitude of 1900
      which it had already reached in 1960. Rainfall should also be considered as a key
      factor in the epidemics. In the Sahel West Africa, temperature increased from 0.5
      degree C to 01 degree C degree in the last 25 years, but rainfall decreased from
      30%. As a result, one of the vector, Anopheles funestus disappeared and malaria
      prevalence dropped by 60 to 80%. It is not acceptable to predict the future
      evolution of malaria in taking in account only one parameter: the temperature.
      The whole factors involved in the epidemiology should be taken into account. The
      predictions based only on the temperature increase (global warming) can be
      totally wrong if the rainfall, for example, decreases.

PMID- 9559168
TI  - [AIDS in Madagascar. I. Epidemiology, projections, socioeconomic impact,
      interventions].
AB  - Madagascar is still among the rare states of low prevalence of HIV. The
      seroprevalence rate is nevertheless rising. The aim of this study is to show the
      current view of the epidemic, its future tendency, its economical and social
      impact on people and what measures to be taken at the national scale. In
      Madagascar, we can state by 1995 20 cases of notified AIDS and probably 130 cases
      of non-notified AIDS. Seroprevalence data are collected every year by the
      National Reference Laboratory STD/AIDS. But, they are insufficient to estimate
      the number of infected people. So, they had been completed by a serosurveillance
      study of AIDS and syphilis in middle of 1995 and at the beginning of 1996.
      Pregnant women, persons with STDs and prostitutes are been screened in the six
      biggest cities of the Island. Results show, not only a high prevalence of
      syphilis, but also indicate that now, we have about 5,000 seropositive people in
      the country. Besides, by the number of people with STDs, it is estimated that one
      million Malgasy adults risk to be infected. Based on estimates of the epidemic,
      be it the cases of a high scenario, (Kenya) or of a low one (Thailand) by the
      year 2015, the seroprevalence rate could represent 3% or 15% of adults.
      Demographic consequences of the epidemic will be serious, particularly if HIV
      spreads quickly. Nevertheless, it does not stop the increase of population.
      Therefore, there will be more infected people with the disease, especially young
      people between 15 and 49 years old. The increase of dead people will be serious.
      Social consequences of the epidemic (case of high scenario) will be gravely felt,
      in particular by the rise of the number of AIDS orphans. Tuberculosis outbreak
      can be observed too. This disease is already a serious problem in Madagascar. At
      last, the epidemic will bring with it a high increase of money spent on health
      and will have grave consequences on agriculture, industry and commerce.
      Nevertheless, Madagascar still benefit a big luck which is the prevention of the
      epidemic not to be exploded in a near future. For this, struggle against it is
      particularly effective on its start. In addition to counselling given to infected
      people and care-given to patients, means of prevention of AIDS contamination in
      all target groups must be set up quickly. It is about broadcasting information on
      AIDS, community education, controlling other STDs e.g. (importance of
      medicaments' program), promoting the use of condoms and screening HIV new cases.
      Only an urgent coordination of everyone's efforts can control the epidemic of
      AIDS.

PMID- 9559169
TI  - [Aids in Madagascar. II. Intervention policy for maintaining low HIV infection
      prevalence].
AB  - The HIV seroprevalence per 100,000 adults Malagasy rose from 20 in 1989, to 30 in
      1992, and to 70 in 1995. In that year, the total number of HIV infected people in
      the Big Island was estimated at 5,000, the number of people sick with AIDS at
      130, and the people at risk at more than 1,000,000. The latter are the persons
      infected with other STDs and individuals (or their partners) with risky sexual
      behaviour (e.g. numerous sexual partners, occasional sexual partners, and/or
      sexual contacts with commercial sex workers). The HIV prevalence rate is low as
      compared with those of other countries. Nevertheless, the spread of the HIV
      infection is alarming in some parts of the country and the risk factors are also
      present, namely: the high prevalence of STDs, numerous sexual partners, the low
      use of condoms in all groups, the development of tourism, the development of
      prostitution associated with social and economical problems, and internal and
      international migrations (with risky sexual contacts). Therefore, the still low
      but rising HIV prevalence in 1995 does not warrant complacency. To estimate the
      trend of HIV prevalence within the population, it is useful to know two different
      assumptions, as follows: firstly, a controlled evolution of the epidemic (low
      epidemic) and secondly, a very fast spread of the epidemic (high epidemic). If we
      consider the 5,000 individuals seropositive in July 1995, the Aids Impact Model
      (AIM) projection model shows that HIV seroprevalence rates among adults in 2015
      might be between 3% (when the progression course of HIV epidemic is low) and 15%
      (when the progression course of HIV epidemic is high). By 2015 AIDS could have
      severe demographic, social, and economic impacts. Then, it is necessary to take
      measures to prevent contamination. Five major interventions are required: public
      information about AIDS, HIV transmission mechanism, and its prevention,
      communities education via the respected people and the notabilities to promote
      moral values, reduce the number of sexual partners, delay visit of sexual
      activity, and advice for infected couples; screening of blood donors and the
      supposed high risk group; control of STDs; reduction of the number of sexual
      partners; promotion of condom use, abstinence, and fidelity. To sum up, the fight
      against AIDS is not only the health professional workers' problem. It concerns
      all Malagasy people. Therefore, successfullness in prevention efforts to slow the
      epidemic needs concerted, collective, and long lasting actions from all sectors
      of the society for the nation's future and the well-being of the rising
      generations.

PMID- 9559170
TI  - [Epidemiologic study of the main human intestinal nematodes in the middle west of
      Madagascar].
AB  - An epidemiological study of human intestinal helminthiasis was conducted during
      July and August 1995, in the middle west of Madagascar, with 4571 adults and
      children ranging from six months to 90 years, in 61 communities between Betafo
      and Miandrivazo. Faecal examination utilising the MIF concentration method
      revealed that ascariasis was the dominant nematodosis in the middle west with
      high prevalences in the high-altitude communities. Ascaris lumbricoides
      prevalences increase among children and women. Interesting more than 50% of the
      pattern, ascariasis is a public health problem and its association with infant
      malnutrition is statistically significant. Hookworm infection prevalence is
      higher in low-altitude communities, it increases among adults. The Trichuris
      trichiura prevalences were lower than the prevalences of ascariasis and hookworm
      infection in all of the communities. Important variations of the prevalences of
      intestinal helminthiasis are observed essentially in relation with climatic
      conditions.

PMID- 9559175
TI  - [Impact of antivectorial control on malarial morbidity and mortality in a health
      district of the Madagascar highlands].
AB  - After the dramatic increase of malaria infections from 1985 to 1988 in the
      Highlands of Madagascar, the vector control programme was reactivated. In order
      to evaluate the impact of this strategy in the district of Arivonimamo, we have
      analysed the morbidity and the mortality data collected in all the health care
      centers of this district. Since 1988, extensive residual house spraying has been
      carried out on a yearly basis in the eastern part of this district whereas the
      western part was not included in this spraying programme. Data from each area
      were compared. In the eastern part, a dramatic decrease of morbitity and
      mortality related to malaria was observed, the benefit was 69% of expected simple
      cases, 87% of expected serious cases and 40% of expected deaths due to malaria.
      It has to be noted that only presumptive cases have been reported since no
      laboratory facilities are available in these health centers. Nevertheless such
      findings provide strong support to the continuation of the spraying programme,
      maybe in a less intensive way, together with an accurate epidemiological
      surveillance.

PMID- 9559179
TI  - [Importation of Plasmodium falciparum malaria, in Reunion Island, from 1993 to
      1996: epidemiology and clinical aspects of severe forms].
AB  - Located in the Indian ocean, Reunion island, a French overseas territory, is free
      of malaria since the 1960's. As malaria is still highly endemic in the
      neighbouring countries, imported cases are averaging 130 to 150 cases per year.
      From 1993 to 1996, about 483 cases of imported malaria were admitted in Reunion.
      Five severe complicated Plasmodium falciparum malaria cases occurring in non
      immune persons, required further treatment in the intensive care unit (age 40 +/-
      8 years, duration: 14.8 +/- 7.4, SAPS: 21 +/- 10). Three patients died. As short
      stay travellers, patients were contaminated in Madagascar (4) and in Malawi (1)
      and presented with an associated pathology: alcohol and tobacco abuses (2 cases),
      AIDS (1 case). In all cases, chemoprophylaxis was either inadequate (chloroquine
      alone, 3 cases) or absent (2 cases) and the diagnosis and the appropriate
      treatment were delayed. Moreover, patients were either self-treating themselves,
      or initially refused to be admitted. Parasitemia was very high. Two patients died
      within an hour following their admission before diagnosis could be made and
      quinine treatment be initiated (rupture of the spleen, multiple organ failure).
      One patient died at day 7 (acute respiratory distress syndrome, renal failure).
      Two survived under respiratory assistance and hemodialysis and presented the
      usual intensive care complications (respiratory nosocomial infection, acute
      cholecystitis). In Reunion island, imported P. falciparum still accounts for a
      high rate of morbidity and few fatalities, despite a sophisticated curative
      health system. Delay in diagnosis and institution of an appropriate treatment is
      frequent in non-immune persons who develop fever and non-specific symptoms. It
      markedly increases the risk of complications and death from falciparum malaria as
      well as morbidity cofactors. Emphasis must be placed on appropriate information
      of health personnel and travellers.

PMID- 9559180
TI  - [Human diseases transmitted by Culicidae in southwest Indian Ocean islands].
AB  - South-West Indian Ocean islands were inhabited at the beginning and free from all
      kind of vector. In Madagascar, Mayotte, Moheli and Anjouan, malaria vectors were
      carried by the first settlements. According to epidemics, the anopheles arrived
      in 1867 in Mauritius, 1869 in La Reunion and 1920 in Grande Comore. Rodrigues,
      Saint-Brandon and the Seychelles are still free from malaria vectors in the
      coastal part of Madagascarcar and in Comores archipelago, malaria is stable with
      a permanent transmission. Unstable malaria is seasonaly transmitted in the high
      territories of Madagascar; it was the same in Mauritius and Reunion island before
      the eradication campaign. Lymphatic filariasis is quoted in Madagascar, but
      Comores archipelago is an area with high transmission. The incidence of the
      disease is moderate in La Reunion and Mauritius and very low in Chagos and
      Seychelles archipelagos. There is no transmission in Rodrigues and St Brandon.
      Epidemics of dengue were described during the second part of the XIXth century in
      Mauritius and La Reunion, then in 1943 in Mayotte. But the disease was controlled
      in the fifties by the antimalaria campaign. A new epidemy appeared in Seychelles
      by the end of 1976 and then in Reunion and Mauritius next year. An isolated
      outbreak was described in Grande Comore only in 1994.

PMID- 9559181
TI  - [A great Franco-Mauritian epidemiologist: Joseph Desire Tholozan (1820-18970].
AB  - Born in 1820 from French parents in Diego Garcia, an islet then linked to
      Mauritius where he started in Port-Louis his school years, Joseph Desire Tholozan
      was an original personality. He undertook medical studies in France (M. D.
      thesis, Paris, 1843) after having joined the military Health Service (1841) as a
      surgeon serving in various garrisons in the country and later at the Hospital of
      the Valde-Grace in Paris (1849). Successful at the "agregation" of Medicine in
      1853, he later participated to the Crimean War (1854-1855) where he performed
      interesting medical observations. In 1858, he was appointed personal physician to
      Nasreddin Shah and remained in Persia until his death in Teheran (1897) where he
      is buried. Tholozan published between 1847 and 1892 over fifty articles and books
      dealing chiefly with infectious pathology and epidemiology, written at a time
      when microbial etiology and specificity of such diseases were wholly unknown. He
      considered chiefly bubonic plague, studying as soon as 1871 the focus of the
      Iranian Kurdistan, a research which will be resumed by M. Baltazard and his
      collaborators between 1947 and 1971, i.e. a century later. He was also deeply
      interested by the "oriental" cholera of which he recalled masterly the history
      and geography in the Near and Middle East. He also performed, while in Crimea and
      Persia, personal observations on tuberculosis, diptheria, remittent fever,
      acrodynia and had studied in France in his early years various other diseases
      such as cutaneous staphylococcic infections, glanders, pulmonary haemorrhagies,
      etc. In Persia, he reorganized Public Health and medical teaching and educated
      many local physicians and surgeons. Being assured of the unlimited confidence of
      the Shah, he played an important cultural role, promoting French influence in
      Persia. Holder of many French and foreign decorations, Tholozan was Fellow of the
      French Academies of Sciences and Medicine. His name was given by Laboulbene to
      Ornithodoros tholozani, a tick vector of a recurrent fever (spirochetosis due to
      Borrelia persica), of which he had described both the symptoms and the vector in
      1882.

PMID- 9559182
TI  - Surgical skills for family physicians. Do family physicians make the cut?

PMID- 9559183
TI  - Well-baby care in the new millennium. Evidence-based care and the new Rourke Baby
      Record.

PMID- 9559184
TI  - Flaws in critical appraisal.

PMID- 9559185
TI  - Protecting patients against "quackery".

PMID- 9559186
TI  - Opportunity for change.

PMID- 9559187
TI  - Is topical tretinoin safe during the first trimester?
AB  - QUESTIONOne of my patients conceived while using a topical tretinoin preparation
      for acne. I know this drug is related to Accutane, which is teratogenic. How
      should I advise her?ANSWERAvailable evidence suggests that topical tretinoin does
      not increase teratogenic risk in humans.

PMID- 9559188
TI  - Ophthaproblem. Macular hole.

PMID- 9559189
TI  - Dermacase. Phytophotodermatitis.

PMID- 9559190
TI  - Strategy to prevent recurrent homelessness among the mentally ill.

PMID- 9559191
TI  - Cost-effective management of patients with dyspepsia.

PMID- 9559193
TI  - Practice choices of graduating family medicine residents.
AB  - OBJECTIVE: To examine the types of practices family medicine residents chose
      during the first 2 years after residency, and how these choices have changed over
      a 15-year period. DESIGN: Mailed survey. SETTING: Areas served by graduates of
      the Queen's University family medicine residency program. PARTICIPANTS: Two
      hundred thirty (76%) of the 303 graduates from 1977 to 1991 of the Queen's
      University family medicine residency program responded to the questionnaire. MAIN
      OUTCOME MEASURES: Type of practices residents entered immediately out of
      residency: whether they began full-time, part-time, locum tenens, or other type
      of practice; length of time spent in the first practice situation; and proportion
      of residents who had settled into a full-time practice within 2 years of
      completing residency. RESULTS: Residents who graduated before 1985 were
      significantly more likely to go into full-time practice immediately out of
      residency (P = .0001). The earlier residents had graduated from the program, the
      more likely they were to go immediately into full-time practice. This finding was
      not affected by residents' age, sex, size of community of origin, exposure to
      rural teaching sites, marital status, or how well prepared for practice they
      felt. Residents graduating before 1985 were also more likely to be in full-time
      practice within 2 years of completing their residency program (P = .003).
      CONCLUSIONS: Recent family medicine residents did not enter full-time practice
      immediately out of residency as often as those who had graduated earlier, nor did
      they commit to full-time practice within 2 years of graduating as often as
      residents graduating before 1985 did.

PMID- 9559192
TI  - Procedures in ambulatory care. Which family physicians do what in southwestern
      Ontario?
AB  - OBJECTIVE: To determine how often family physicians perform 12 ambulatory care
      procedures and factors associated with procedure performance. DESIGN: Mailed,
      self-administered survey. The survey was conducted according to the Dillman Total
      Design method. SETTING: Family physicians' offices in London, Ont, and in
      surrounding communities. PARTICIPANTS: A total of 395 family physicians
      practising within the London area were mailed surveys, 237 in London and 158
      outside London. Response rates were 80.6% and 75.9%, respectively. Nonresponders
      did not differ significantly from responders in sex but included more solo
      practitioners. MAIN OUTCOME MEASURES: Performance of ambulatory care procedures,
      sex, and practice characteristics of participant family physicians. RESULTS: For
      all responders, activities significantly associated with procedure performance
      were delivering babies, managing psychological problems, working emergency, and
      teaching. Mean total procedure scores ranged from 6.55 for managing psychological
      problems to 7.68 for working emergency. Sex-specific analysis showed that
      practice location and years in practice were significant factors for female but
      not for male family physicians. Mean total procedure scores for female physicians
      were 7.06 (outside London) and 4.74 (in London). CONCLUSIONS: Factors associated
      with procedure performance for family physicians in and around London included
      delivering babies, working in emergency, managing psychological problems, and
      teaching. Practice location was a significant factor for only female family
      physicians; those practising outside London performed procedures more than their
      urban counterparts and at similar rates to male physicians.

PMID- 9559194
TI  - Participation in CME activities.
AB  - OBJECTIVE: To compare the continuing medical education (CME) activities of family
      physicians in the province of Quebec with more than 25 years in practice with
      those with less than 25 years in practice. DESIGN: Mailed questionnaire survey.
      SETTING: Family practices in the province of Quebec. PARTICIPANTS: All physicians
      (n = 722) with more than 25 years in practice (expressed as older) and a matched
      sample of 721 physicians with less than 25 years in practice (expressed as
      younger). MAIN OUTCOME MEASURES: Types of CME activities and time spent on them,
      participant characteristics. RESULTS: Older physicians spent more time in
      individual CME activities than younger ones (21 hours vs 18 hours monthly).
      Younger physicians, however, spent more time in group CME activities than older
      ones did (100 hours vs 80 hours yearly). Excluding physicians who devoted no time
      to CME activities, only two activities differentiated between the two groups:
      older physicians spent more time than their younger colleagues reading and
      listening to audiocassettes. CONCLUSIONS: Older physicians maintained their
      clinical competence by participating in different CME activities from younger
      physicians. They participated in as many CME activities as their younger
      colleagues.

PMID- 9559195
TI  - Trends in vasectomy. Analysis of one teaching practice.
AB  - PROBLEM BEING ADDRESSED: How can a teaching practice develop a referral service
      and incorporate educational opportunities for family medicine residents, clinical
      clerks, and community family physicians? OBJECTIVE OF PROGRAM: To develop a high
      quality vasectomy service within a teaching practice to change the surgical
      procedure to the no-scalpel vasectomy (NSV) technique; to educate family medicine
      residents, clinical clerks, and community family physicians about vasectomy and
      the NSV technique; and to monitor outcomes and compare them with published
      results. MAIN COMPONENTS OF PROGRAM: The program took place in an urban family
      medicine residency program. Data on number of procedures, types of patients
      choosing vasectomy, and outcomes are presented, along with information on number
      of learners who viewed, assisted with, or became competent to perform NSV.
      CONCLUSIONS: A few family medicine residents and some interested community
      physicians could be trained to perform NSV competently. Involving learners in the
      procedure does not seem to change the rate of complications.

PMID- 9559196
TI  - Evidence-based well-baby care. Part 1: Overview of the next generation of the
      Rourke Baby Record.
AB  - PROBLEM BEING ADDRESSED: Well baby and child care in the primary care setting has
      not always been based on evidence that has been shown to be effective in
      preventing and detecting disease and injury. OBJECTIVE OF THE PROGRAM: To help
      physicians and nurses provide care that is more effective than a routine complete
      examination, the Rourke Baby Record has been revised to include evidence-based
      recommendations for preventive care for infants and young children. The revision
      incorporates the approach and recommendations of the Canadian Task Force on the
      Periodic Health Examination. The updated record is now called the Rourke Baby
      Record: Evidence-Based Infant/Child Health Maintenance Guide (Rourke Baby Record:
      EB). MAIN COMPONENTS OF PROGRAM: Part 1 of this two-part article briefly
      describes the background for development and presents an overview of the revised
      record. Part 2 discusses in detail the evidence that exists for maneuvers
      included in the education and advice section of the revised record. CONCLUSION:
      Using the Rourke Baby Record: EB and incorporating it into their office record
      systems as a working guide will help increase the effectiveness of the primary
      preventive care physicians provide to infants and young children.

PMID- 9559197
TI  - Evidence-based well-baby care. Part 2: Education and advice section of the next
      generation of the Rourke Baby Record.
AB  - PROBLEM BEING ADDRESSED: Well baby and child care in the primary care setting has
      not always been based on evidence that has been shown to be effective in
      preventing and detecting disease and injury. OBJECTIVE OF THE PROGRAM: To help
      physicians and nurses provide care that is more effective than a routine complete
      examination, the Rourke Baby Record has been revised to include evidence-based
      recommendations for preventive care for infants and young children. The revision
      incorporates the approach and recommendations of the Canadian Task Force on the
      Periodic Health Examination. The updated record is now called the Rourke Baby
      Record: Evidence-Based Infant/Child Health Maintenance Guide (Rourke Baby Record:
      EB). MAIN COMPONENT OF PROGRAM: Part 2 of this two-part article discusses the
      maneuvers included in the education and advice section of the record. These
      maneuvers are discussed under the subheadings safety, behaviour, family coping,
      high-risk children, and other. CONCLUSION: Using the Rourke Baby Record: EB and
      incorporating it into their office record systems as a working guide will help
      increase the effectiveness of the primary preventive care physicians provide to
      infants and young children.

PMID- 9559198
TI  - Case report: retinal detachment associated with atopic dermatitis.

PMID- 9559199
TI  - Canadian breast cancer initiative. One way to help women living with breast
      cancer.

PMID- 9559200
TI  - Canadian Perinatal Surveillance System.

PMID- 9559201
TI  - Eat well, live well. Time to promote healthy eating.

PMID- 9559202
TI  - Articulating a message. Presentation skills for family physicians.

PMID- 9559203
TI  - Our strength for tomorrow: valuing our children. Part 8: Addressing the
      determinants of health. CFPC's task force on child health.

PMID- 9559204
TI  - Preventing another blood scandal. How can family physicians help?

PMID- 9559205
TI  - Gastroesophageal reflux disease.
AB  - Chronic GERD is an unremitting, incurable disorder that recurs rapidly upon
      discontinuation of therapy. Primary complications of GERD include esophagitis,
      esophageal stricture and Barrett esophagus. Current therapy focuses on modifying
      risk factors, inhibiting the production of acid and enhancing esophageal gastric
      motility. In patients with uncomplicated heartburn, nondrug therapy should be the
      initial therapeutic approach, with patient education a major step in promoting
      lifestyle changes and improving the outcome. Maintenance therapy is central to
      the management of GERD. If symptoms persist to suggest complicated disease,
      further diagnostic tests (endoscopy) are indicated. H2 receptor antagonists
      usually resolve symptoms in 50% to 70% of patients, and PPIs in 74% to 96% of
      patients. Agents that improve esophageal motility, such as cisapride, may provide
      symptomatic relief of heartburn, but healing effects are inconsistent. In
      refractory disease, therapy is individualized to the patient, and may include
      combination therapy, more aggressive single line therapy or an appropriate
      surgical approach.

PMID- 9559206
TI  - Utility of serology in determining Helicobacter pylori eradication after therapy.
AB  - OBJECTIVE: To determine the usefulness of four serological tests in confirming
      cure of H pylori infection before the previously reported six-month post
      treatment delay. PATIENTS AND METHODS: As part of a prospective, blinded,
      controlled trial, in which patients with duodenal ulcers were randomized to
      receive different combinations of antibiotics, serum samples were obtained in 89
      patients before treatment, as well as on several occasions after treatment.
      Antibody titres were determined by ELISA with Bio-Rad immunoglobulin (Ig) A, Bio
      Rad IgG, Pyloriset EIA-A for IgA and Pyloriset EIA-G for IgG. Eradication was
      confirmed with antral biopsy three months after therapy. RESULTS: The percentage
      drop in titre following treatment was significantly larger for the group of
      patients who were treated successfully with all four kits. Optimal cut-offs for
      identifying successful therapy were determined, and accuracy improved as the
      interval between testing and therapy was prolonged. Six months after therapy, the
      IgG test from Bio-Rad achieved 100% sensitivity and 80% specificity, and that
      from Pyloriset achieved 88% sensitivity and 100% specificity. At three months,
      however, test performance was quite good, with 90% sensitivity and 80%
      specificity when using a Pyloriset IgA titre drop of 20% or greater to predict
      successful eradication. CONCLUSION: Serology is a simple, easily available,
      noninvasive method that exhibits good positive predictive value in the
      confirmation of successful cure of H pylori infection three or six months after
      treatment.

PMID- 9559207
TI  - Postliver transplant allograft reinfection with a lamivudine-resistant strain of
      hepatitis B virus: long-term follow-up.
AB  - Lamivudine is a nucleoside analogue with efficacy in the suppression of hepatitis
      B viral (HBV) replication. In a previously reported study, lamivudine was
      administered to patients with chronic, actively replicating HBV infection who
      subsequently underwent liver transplantation. Patients became serum HBV DNA
      negative in response to lamivudine before transplantation, which was continued in
      the post-transplant period. Two of four patients surviving the immediate
      postoperative period developed allograft reinfection 240 and 409 days post
      transplant. The strain of the reinfecting virus was analyzed, and a mutation in
      the YMDD region of the viral polymerase conferring resistance to lamivudine was
      discovered. The long term follow-up of these two patients is reported. The first
      patient developed ascites 16.5 months after allograft reinfection. A transjugular
      liver biopsy performed 18 months after the emergence of the lamivudine-resistant
      strain revealed cirrhosis and lobular hepatitis without rejection. The gradient
      between hepatic vein wedged and free pressures was 13 mmHg, consistent with
      portal hypertension. The second patient, 16 months after allograft reinfection
      with the lamivudine-resistant strain, is without clinical evidence of portal
      hypertension, although liver enzymes remain elevated. Both patients were given a
      trial of famciclovir, which did not significantly suppress HBV viremia. In
      conclusion, lamivudine-resistant HBV strains with the YMDD mutation may have an
      aggressive clinical course with rapid progression to cirrhosis. Famciclovir did
      not appear to be an effective rescue agent in these two patients.

PMID- 9559209
TI  - Survey of gastroenterologists on the diagnosis and treatment of adult patients
      with celiac disease in British Columbia.
AB  - A recent survey of physician specialists from New York City suggested that few
      patients with celiac disease are seen and that management experience is limited.
      The present study, using a survey similar to that of the New York City
      investigation, evaluated the diagnostic and management experience of specialists
      for adult celiac disease patients in British Columbia. Four hundred and four
      patients were reported in the combined clinical practice experience of the
      responding physicians. Of these, 59, or 15%, were diagnosed in the prior year.
      Although each physician diagnosed an average of 2.4 new celiac disease patients
      per year in their entire practice experience, an average of over 4.0 new celiac
      disease patients were detected in the past year. Most patients presented with
      diarrhea, weight loss, anemia or nutrient deficiency, but about 14% were
      asymptomatic or diagnosed by an incidental small intestinal biopsy done at upper
      gastrointestinal endoscopy. Specialist physicians in British Columbia usually
      refer patients to their family physicians, dietitians and patient support groups
      for continued care and appear to rarely rely on serological assays, including
      antibody tests, for detection of celiac disease in adults. An associated or
      complicating lymphoma was detected in 16 of 404 patients (4%). Recognition of
      biopsy-defined celiac disease appears to be increasing in British Columbia.

PMID- 9559210
TI  - Setting the stage for the new graduate.

PMID- 9559211
TI  - An ethicist's commentary on the dog being used to carry drugs.

PMID- 9559208
TI  - Altered colonic environment, a possible predisposition to colorectal cancer and
      colonic inflammatory bowel disease: rationale of dietary manipulation with
      emphasis on disaccharides.
AB  - A recurrent theme in the schema of pathogenetic mechanisms attributed to
      colorectal cancer (CRC) and inflammatory bowel disease (IBD) is the interaction
      between genes and environment. Dietary and other environmental factors, and lower
      intestinal flora and their chemical interactions occur in the pathogenesis of
      both. Events at the mucosal surface may be influenced by factors in the luminal
      environment and by contributions of the host. In addition, both forms of IBD-
      Crohn's disease (CD) and ulcerative colitis (UC)--have distinctive associated
      host events. Even within CD and UC, different clinical patterns and prognoses may
      have different specific host mechanisms. Some of the current putative
      pathogenetic processes in CRC and IBD are reviewed. Particular attention is given
      to hypotheses relating to the role of dietetic substances, mainly fibre and dairy
      products, and how they may affect disease formation. It is argued that within the
      context of hypotheses proposed for possible beneficial effects of these two
      dietetic factors, CRC and IBD may be considered together. Further support is lent
      to arguments that similar and additional hypothetical features ascribed to
      beneficial effects of fibre may be attributed to disaccharides, lactose and its
      derivatives, lactulose and lactitol.

PMID- 9559212
TI  - The Canadian Animal Health Network: Canada's response to the World Trade
      Organization.

PMID- 9559213
TI  - Comparison of 3 methods of selenium assessment in cattle.
AB  - Three tests are routinely done to assess blood status of selenium in cattle:
      serum selenium, whole blood selenium, and glutathione peroxidase. The objective
      of this study was to compare the various analytical methods for determining blood
      selenium status in groups of mature cows and beef calves. Twenty to 30 blood
      samples per herd were collected from 8 beef herds in central Alberta and 1 dairy
      in Alberta herd twice a year from the spring of 1992 through the fall of 1995,
      and once from 185 spring calves in 2 beef herds in Saskatchewan. Serum and whole
      blood samples were submitted to 1 laboratory and whole blood samples were
      submitted to a 2nd laboratory. Samples for glutathione peroxidase determinations
      were submitted to a 3rd laboratory. Pearson's correlation coefficients and
      Cohen's kappa were calculated for each possible comparison among the different
      measures. The best agreement was observed between serum and whole blood analysis
      within Laboratory A. The remaining comparisons reflected poor agreement.
      Comparison of herd-level assessment resulted in better agreement than comparison
      of individual sample results among laboratories and procedures for all
      combinations tested. Serum selenium analysis was the only laboratory procedure
      for which external reference material was utilized. Serum selenium, whole blood
      selenium, and glutathione peroxidase measure different compartments of the blood
      selenium pool. The time frame of interest, supplementation practices, and the
      stability of recent dietary intake determine the optimum assessment method for
      individual animals or herds. Determination of the serum status or of blood
      selenium is more consistently measured at the herd-level than for individual
      samples.

PMID- 9559214
TI  - Reproductive consequences of an X-autosome translocation in a swine herd.
AB  - A survey was conducted on the chromosome makeup and breeding data of pigs housed
      at the Arkell Research Station, University of Guelph, to determine the
      reproductive impact of a reciprocal translocation previously identified as
      t(Xp+;14q-). Blood samples were cultured and chromosome spreads were examined to
      identify carriers in the herd. Gonadal features of carrier boars and piglets and
      their age-matched normal counterparts were studied, and the reproductive history
      of carrier sows, including the number of breedings required for conception, mean
      litter size, prevalence of still births and malformations, and sex distribution
      among the piglets, was compared with that of normal (noncarrier) sows. Our
      observations on testicular histology confirmed that X-autosome translocation
      carrier boars are sterile, and the analysis of reproductive data showed that the
      most striking effects of t(Xp+;14q-) on sows are the 50% increase in the number
      of breedings required for conception and the over 25% reduction in litter size
      compared with that of normal sows. The reproductive impact of this and similar
      translocations on the herd and on the swine industry in general is discussed.

PMID- 9559215
TI  - Oslerus osleri tracheobronchitis: treatment with ivermectin in 4 dogs.
AB  - Oslerus osleri tracheobronchitis was diagnosed in 4 young dogs following
      endoscopic visualization of tracheal nodules and identification of larvae in
      airway cytologic samples. All dogs improved when ivermectin was administered (200
      400 micrograms/kg body weight); however, most (3/4) required serial treatments in
      order to achieve long-term resolution of clinical signs.

PMID- 9559216
TI  - A different approach to controlling the cat population.

PMID- 9559217
TI  - History and clinical signs.

PMID- 9559218
TI  - Bioluminescence-based assays for detection and characterization of bacteria and
      chemicals in clinical laboratories.
AB  - OBJECTIVES: To survey recent advances in the application of bioluminescence to
      public health problems. The usefulness of bacterial (lux) and eucaryotic (luc)
      luciferase genes is presented, along with several examples that demonstrate their
      value as "reporters" of many endpoints of clinical concern. CONCLUSIONS: The
      development of new technologies for monitoring biological and chemical
      contaminants is in continuous progress. Recent excitement in this area has come
      from the use of genes encoding enzymes for bioluminescence as reporter systems.
      Applications of the recombinant luciferase reporter phage concept now provide a
      sensitive approach for bacterial detection, their viability, and sensitivity to
      antimicrobial agents. Moreover, a number of fusions of the lux and luc genes to
      stress inducible genes in different bacteria can allow a real-time measurement of
      gene expression and determination of cellular viability, and also constitute a
      new tool to detect toxic chemicals and their bioavailability.

PMID- 9559219
TI  - Establishing reference intervals for DPC's free testosterone radioimmunoassay.
AB  - OBJECTIVE: To establish reference intervals for serum free testosterone for DPC's
      Free Testosterone assay. METHODS: We used data from healthy subjects and patients
      to determine reference intervals by parametric and non-parametric methods after
      partitioning by sex and age. RESULTS: In males, there was a significant decrease
      in free testosterone concentrations with age. Reference intervals derived from a
      combination of 2075 "healthy" and patients' results gave similar values by
      parametric and nonparametric methods. However, the subgroups failed the test for
      Gaussian distribution. For each decade from 20 years on and > or = 60 years, the
      intervals based on 2.5th and 97.5th percentiles were: 24.1-94.8, 25.0-89.3, 23.4
      81.7, 22.5-80.4, and 21.5-74.3 pmol/L respectively, in females, there was little
      change with age. The frequency distribution of 1915 patients was positively
      skewed, and showed a wider range than "healthy." Using square roots of values
      gave a Gaussian distribution. The central 95% intervals based on 187 "healthy"
      subjects were: 0.5-8.1 and 0.0-6.4 pmol/L for 20-59 and > or = 60 years,
      respectively. CONCLUSION: Developing reference intervals for free testosterone
      was complicated by the need to partition data by gender and age, difficulty in
      establishing disease in subjects and presence of physiological and other factors
      which can affect concentration in health and disease.

PMID- 9559220
TI  - Analytical evaluation of the testosterone assay on the Bayer Immuno 1 system.
AB  - OBJECTIVES: To evaluate the analytical performance of the testosterone assay
      performed on the Bayer immuno 1 system from Bayer Corporation. DESIGN AND
      METHODS: The precision was measured using three Bayer TESTpoint Ligand controls,
      three Medical Decision Pools and the Bayer SETpoint Testosterone calibrators. The
      linearity was verified by diluting two serum samples containing high testosterone
      concentrations with the zero calibrator and the minimum detectable concentration
      determined by repetitive analysis of the zero calibrator. The assay was
      correlated with the Diagnostic Products Corporation (DPC) Total Testosterone
      assay using 342 serum samples. The reference values were determined using serum
      samples from 75 women and 60 men. RESULTS: The assay showed within-run
      coefficients of variation (CVs) varying from 1.1-8.4% and between-day CVs from
      1.5-4.9% for testosterone concentrations varying from 1.77 to 66.96 nmol/L. The
      minimum detectable concentration was estimated at 0.11 nmol/L. The assay
      linearity proved excellent. A good correlation between the Bayer Immuno 1 and the
      DPC assays was observed with different categories of serum samples (Immuno 1 =
      1.11 x DPC-0.32, r = 0.989, Sy[symbol: see text]x = 2.07 nmol/L). The reference
      values were estimated at 0.3-3.2 nmol/L for females and 9.3-35.6 nmol/L for
      males. CONCLUSIONS: The Bayer Immuno 1 Testosterone assay demonstrates the
      analytical characteristics required for its utilization in the clinical
      laboratory.

PMID- 9559221
TI  - A simple spectrophotometric enzyme assay with absolute specificity for
      arylsulfatase A.

PMID- 9559222
TI  - Correlation of sweat chloride concentration with genotypes in cystic fibrosis
      patients in Saguenay Lac-Saint-Jean, Quebec, Canada.
AB  - OBJECTIVES: Saguenay Lac-Saint-Jean, a geographically isolated region of
      northeastern Quebec has a high incidence of cystic fibrosis (CF) and three
      mutations only account for 94% of the CF chromosomes. The objective of the
      present study was to determine whether different mutations in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene had different effects upon the
      sweat chloride concentration. DESIGN AND METHODS: The sweat chloride
      concentration of 114 patients was measured by quantitative pilocarpine
      iontophoresis. RESULTS: CF patients carrying the A455E mutation, usually
      associated with pancreatic sufficiency, had lower sweat chloride concentrations
      than those carrying mutations associated with pancreatic insufficiency (delta
      F508 and 621 + 1G-->T). CONCLUSIONS: Our results confirm that mutations resulting
      in a reduction of the chloride current at the apical membrane of epithelial cells
      induce lower sweat chloride values. However, there are differences in the
      chloride current between genotypes, even if they are composed of mutations
      apparently having the same functional effect.

PMID- 9559223
TI  - Effects of antihypertensive drugs on cholesterol metabolism of human mononuclear
      leukocytes and hepatoma cells.
AB  - OBJECTIVES: Primary prevention trials of antihypertensive therapy have shown
      conflicting results on coronary events. Potential interference of
      antihypertensive agents with cellular lipid metabolism may alter the
      atherosclerotic risk of individuals. DESIGN AND METHODS: The effects of the
      calcium antagonist's verapamil, diltiazem, and nifedipine and of the beta
      blockers propranolol and metoprolol on low density lipoprotein (LDL) receptor
      activity, cholesterol esterification rate, oleate incorporation in triglycerides
      and sterol synthesis were studied in freshly isolated human leukocytes and HEP G2
      cells. RESULTS: Up to a concentration of 3-10 mumol/L, verapamil, propranolol,
      and metoprolol led to an increased cellular content of 125I-LDL by an inhibition
      of degradation. In mononuclear cells verapamil stimulated accumulation and
      degradation. No effect on binding was observed. Diltiazem was only stimulatory on
      125I-LDL processing in leukocytes. Beta blockers and verapamil significantly
      reduced the LDL mediated 14C-oleate incorporation in cholesterol esters. In the
      presence of 25-hydroxycholesterol the esterification was not diminished, which
      suggests that cholesterolacyltransferase (ACAT) was not affected per se. Whereas
      all the agents induced the synthesis of lanosterol, metoprolol inhibited
      cholesterol synthesis. None of the agents had a significant influence on 14C
      oleate incorporation in triglycerides, suggesting a specific influence on
      cholesterol metabolism. CONCLUSIONS: Antihypertensive drugs affect the
      cholesterol metabolism on a cellular level. Mechanisms are an interference with
      degradation of LDL and consequent alterations of cholesterol esterification.
      Using leukocytes as peripheral cells and HEP G2 as a model of human liver, these
      results may have importance when antihypertensive long-term therapy is conducted
      for primary or secondary prevention of atherosclerotic complications.

PMID- 9559224
TI  - Laboratory survey of prostate specific antigen testing in Ontario.

PMID- 9559225
TI  - Patients with suspicious digoxin levels: evaluation of the potential contribution
      of crossreactive digoxin metabolites.

PMID- 9559226
TI  - Multicenter evaluation of the Abbott AxSYM procainamide and N-acetylprocainamide
      assays: comparison with Abbott TDx/TDxFLx, Syva EMIT 2000, DuPont ACA, and HPLC
      methods.

PMID- 9559227
TI  - US and CT findings of secondary neoplasms of the thyroid--a pictorial essay.
AB  - Although clinical series report a low (3%) incidence of metastases to the thyroid
      gland, autoptic studies have showed occurrences as high as 17%, probably because
      of the high vascularization of the thyroid. We selected 9 patients who had
      pathologically proven thyroid metastases at CT and US, during follow-up for a
      known primary neoplasm. The most common originating neoplastic primaries include
      mostly those that generally give rise to blood-borne metastases such as breast
      and lung cancers, mucoid adenocarcinoma of the stomach, colon cancer and renal
      cancer, as well as melanoma and leiomyosarcoma. Because of its diffusion,
      sensitivity, and noninvasiveness, ultrasonography can justifiably be introduced
      in the staging protocols of those neoplasm that more frequently give blood-borne
      metastases to the thyroid, but a US-guided biopsy is warranted for hypoechoic or
      otherwise suspicious nodules. This holds particularly true in disease-free
      patients or previously diagnosed with generally slow-growing malignancies (breast
      or kidney), since the secondary localization, often metachronous in our
      experience, may be effectively managed surgically. CT features, on the other
      hand, are extremely variable and are directly dependent on the histology of the
      primary lesion, as well as the size of the secondary lesions.

PMID- 9559228
TI  - Contrast-enhanced breast MRI for cancer detection using a commercially available
      system--a perspective.
AB  - The diagnosis and treatment of breast cancer are dependent upon early detection
      of the disease by physical examination and mammography. Although mammography is a
      relatively good and cost-effective method of early breast cancer detection, there
      are some inherent weaknesses associated with this imaging modality that limit its
      sensitivity and specificity. Contrast-enhanced MRI of the breasts provides the
      additional capability to answer questions raised or unanswered with conventional
      imaging methods. This paper reviews contrast-enhanced breast MRI interpretation
      guidelines and patient preselection criteria for diagnostic problem cases.
      Technical aspects using a commercially available three-dimensional (3D) spoiled
      gradient-echo technique are discussed.

PMID- 9559229
TI  - Differential diagnosis of hepatic tumors with delayed enhancement at gadolinium
      enhanced MRI: a pictorial essay.
AB  - Hepatic lesions with delayed enhancement are sometimes encountered on gadolinium
      enhanced MRI of the liver. This study illustrates the varied appearances of
      several pathologic entities with delayed enhancement, including hepatic
      hemangioma, hepatic metastases, intrahepatic cholangiocarcinoma, focal nodular
      hyperplasia, hepatic abscess, hepatocellular carcinoma, and hepatocellular
      carcinoma after transcatheter arterial chemoembolization, and presents the
      utility of arterial-phase dynamic MRI in the differential diagnosis of these
      lesions. Possible causes of these delayed enhancements are also discussed.

PMID- 9559230
TI  - Neuroimaging on delayed postanoxic encephalopathy with lesions localized in basal
      ganglia.
AB  - A 59-year-old woman suffered from prolonged hypotension with myocardial
      infarction. Sixteen days after the episode, she showed bradykinesia, gait
      disturbance, and postural tremor. MRI revealed low signa intensities in the
      bilateral caudate nuclei and putamen on the T1-weighted image and high signal
      intensities on the T2-weighted image. PET with 18F-FDG revealed a severe decrease
      in glucose metabolism in bilateral basal ganglia. It is concluded that prolonged
      hypotension may induce localized delayed anoxic lesions in basal ganglia.

PMID- 9559231
TI  - Primary malignant pulmonary hemangiopericytoma.
AB  - A primary malignant pulmonary hemangiopericytoma was diagnosed in a 45-year-old
      woman who complained of 10 months of cough and exertional dyspnea. One year after
      resection of the mass, a metastatic lesion was removed from the contralateral
      lung. The literature on this unusual pulmonary lesion is reviewed.

PMID- 9559232
TI  - Direct duodenal invasion of hepatocellular carcinoma. Intestinal hemorrhage
      treated by transcatheter arterial embolization.
AB  - This report describes a case of direct duodenal invasion of hepatocellular
      carcinoma with massive intermittent gastrointestinal (GI) bleeding. Progressive
      anemia was intractable by supportive therapy alone, and repeated blood
      transfusion was necessary. Transcatheter arterial embolization was finally
      carried out, which dramatically reduced the amount of transfusion. Owing to
      severe blood loss, patients with GI tract involvement generally have a poor
      prognosis.

PMID- 9559233
TI  - Differentiation between hepatic cavernous hemangioma and malignant tumor with T2
      weighted MRI: comparison of fast spin-echo and breathhold fast spin-echo pulse
      sequences.
AB  - PURPOSE: The goal of our study was to compare a T2-weighted breathhold fast spin
      echo (BHFSE) technique with T2-weighted nonbreathhold fast spin-echo (FSE)
      technique for characterizing cavernous hemangioma of the liver and
      differentiating this entity from malignant tumor. MATERIALS AND METHODS: Eighteen
      patients with cavernous hemangiomas and 18 patients with malignant hepatic tumors
      were studied with T2-weighted MRI with a nonbreathhold FSE technique with and
      without fat suppression and with a BHFSE technique without fat suppression.
      Hepatic lesions were analyzed quantitatively using signal intensity (SI) and
      contrast-to-noise (C/N) ratio. In addition, images were qualitatively compared
      for accuracy in characterizing hepatic lesion. RESULTS: Quantitatively,
      hemangioma had significantly higher SI and C/N ratios than did the malignant
      tumor on every pulse sequence (P < 0.01). Qualitatively, all malignant tumors
      were correctly categorized; differentiation between cavernous hemangioma and
      malignant tumor was impossible in three cases of cavernous hemangioma with the
      three pulse sequences (92% accuracy, 100% sensitivity, and 83% specificity).
      CONCLUSION: T2-weighted FSE and BHFSE MRI shows comparable levels of accuracy for
      differentiating between hepatic cavernous hemangioma and malignant tumor. Because
      overlap may exist using quantitative measurement, morphologic patterns must be
      carefully analyzed, supporting that quantitative analysis and morphologic
      evaluation are complementary.

PMID- 9559234
TI  - Hepatic adenoma and focal nodular hyperplasia: MR findings with superparamagnetic
      iron oxide-enhanced MRI.
AB  - Two cases are presented in which the MRI findings following superparamagnetic
      iron oxide (SPIO) enhancement of hepatic adenoma and focal nodular hyperplasia
      (FNH) are described. Benign liver lesions show uptake of iron oxide particles,
      which allows differentiation from malignant liver lesions and tumors of other
      cell origin. There have been several publications in the literature, but the SPIO
      enhanced MR findings of hemorrhage in a hepatic adenoma have not been previously
      described. To illustrate the role of SPIO-enhanced MRI in the differential
      diagnosis of adenoma from FNH, the SPIO-enhanced MR features of FNH are
      presented.

PMID- 9559235
TI  - Rheumatoid nodules: MRI characteristics.
AB  - Rheumatoid nodules are not uncommon in patients with rheumatoid arthritis. Two
      patients with rheumatoid arthritis and rheumatoid nodules are described. The MRI
      characteristics and enhancement patterns of five nodules are examined.

PMID- 9559236
TI  - Criminal behavior and mental disorder: impediments to assigning moral
      responsibility.

PMID- 9559237
TI  - A capitated model for a cross-section of severely mentally ill clients:
      hospitalization.
AB  - Hospitalization outcomes are examined in a three year random assignment
      controlled study of two capitated Integrated Service Agencies (ISAs) in
      California. Study participants were a cross-section of severely mentally ill
      clients. Using the flexibility of capitated funding, the urban ISA reduced
      inpatient length of stay and days, but not admissions. Elements of the capitated
      ISA model worked together to produce clinically appropriate and less costly use
      of inpatient services. At the rural ISA, admissions were reduced substantially
      during the first two years of the demonstration but not costs.

PMID- 9559238
TI  - Computerized depression screening and awareness.
AB  - The DEPRESSION Awareness, Recognition and Treatment (D/ART) program under the
      sponsorship of the National Institutes of Health has made consistent efforts to
      help educate many communities around the nation about depression. One important
      aspect of this effort includes offering free screening for depression to the
      general public. Since new technology often promotes curiosity and interest, a
      computerized depression screening and awareness program was created to use at
      fairs and other local events. Individuals who participated completed a
      computerized version of the Center for Epidemiological Studies Depressed Mood
      Scale (CES-D) and then received a one page printout that described the common
      symptoms of depression, a score indicative of their level of depressed mood, a
      brief explanation of the score, and a telephone number where additional
      information could be obtained. This paper details the construction of the
      computerized version of the CES-D including an evaluation of psychometric
      properties and consumer satisfaction with the program.

PMID- 9559239
TI  - An empirical assessment of rural community support networks for individuals with
      severe mental disorders.
AB  - The community support network has been well-established as a requirement for
      community treatment of individuals with severe mental disorders. This network
      generally consists of a multidisciplinary set of organizations that interrelate
      in some manner with individuals in the community. The question of coordination
      within this network has been much discussed; however little published research
      has empirically examined the types and extent of coordination among network
      organizations. In particular, little attention has been given to community
      support networks in rural communities. In each of seven rural counties,
      information was obtained on inter-actions among organizations in the community
      support network. These networks were analyzed to yield information on network
      density and centralization. Using measures of centrality, the most central
      organizations in each network were identified. Exchanges of information were the
      most common type of interaction among organizations in each network. Client
      referrals occurred less frequently, and sharing of resources was an even rarer
      phenomenon. Network analysis of community support networks provides an objective
      perspective on the structure of community support networks. An understanding of
      exchange among organizations within these networks is of value to administrators,
      clinicians, and planners interested in achieving greater effectiveness, as well
      as to patients, their families, and advocacy groups concerned with access and
      quality of care.

PMID- 9559240
TI  - The relationship between housing characteristics, emotional well-being and the
      personal empowerment of psychiatric consumer/survivors.
AB  - In this research, we examine the relationships between the housing
      characteristics and dimensions of community adaptation for 107 psychiatric
      consumer/survivors. Hypotheses about which housing characteristics best predict
      which dimensions of adaptation were made based on previous research and theory.
      Using a longitudinal research design, we found, after controlling for demographic
      variables and prior adaptation, that the number of living companions, housing
      concerns, and having a private room all significantly predicted different
      dimensions of community adaptation. The findings partially support our
      theoretical expectations and illuminate the relationship between physical, social
      and organizational aspects of community-based housing and the adaptation of
      psychiatric consumer/survivors. We discuss the implications of the results for
      policy and practice in providing housing for this population.

PMID- 9559241
TI  - Job terminations among persons with severe mental illness participating in
      supported employment.
AB  - For persons with psychiatric disabilities, maintaining a job is often more
      difficult than acquiring a job. A large proportion of jobs end unsatisfactorily.
      This study explored job terminations among 63 persons with severe mental illness
      who participated in competitive jobs through supported employment programs. More
      than half of the job terminations were unsatisfactory, defined as the client
      quitting without having other job plans or being fired. Baseline ratings of
      demographic and clinical characteristics, preemployment skills training, and
      early ratings of job satisfaction and work environment did not predict
      unsatisfactory terminations. Clients with better work histories were less likely
      to experience unsatisfactory terminations. In addition, unsatisfactory
      terminations were associated retrospectively with multiple problems on the job
      that were related to interpersonal functioning, mental illness, dissatisfaction
      with jobs, quality of work, medical illnesses, dependability, and substance
      abuse. These results suggest that supported employment programs need to address
      job maintenance with interventions that identify and address different types of
      difficulties as they arise on the job.

PMID- 9559242
TI  - A mental health program report card: a multidimensional approach to performance
      monitoring in public sector programs.
AB  - This report presents a comprehensive, multi-dimensional mental health program
      performance monitoring system that has recently been implemented in the
      Department of Veterans Affairs. Principles underlying the development of the
      system are reviewed and 68 specific monitors are described addressing four major
      performance domains: access, inpatient care, outpatient care, and economic
      performance. Simple methods are presented for identifying outliers, for
      generating summary performance scores across series' of related monitors, and for
      adjusting results for differences in patient characteristics across locales.
      Although still technically imperfect, and therefore requiring continuous
      improvement, monitoring systems such as the one presented can be useful tools
      guiding and improving service delivery and mental health system performance, and
      providing a medium of accountability to consumers and other stakeholders.

PMID- 9559243
TI  - Management approaches for mental health program report cards.

PMID- 9559244
TI  - Response to Rosenheck and Cicchetti's "a mental health program report card: a
      multidimensional approach to performance monitoring in public sector programs".

PMID- 9559245
TI  - T-cell technology in the diagnosis & management of cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) is a malignancy of mature, clonal, helper (CD4+)
      T-cells that have a propensity for localizing in the skin. This article discusses
      the new immunologic and molecular advances and their practical application in the
      management of CTCL.

PMID- 9559246
TI  - Systemic lupus erythematosus in pregnancy.
AB  - Systemic lupus erythematosus is an inflammatory autoimmune disease that can
      affect multiple organ systems. The most popular theory regarding the origin of
      its clinical manifestations is that autoantibodies and circulating immune
      complexes become trapped in the capillaries of visceral structures.

PMID- 9559247
TI  - Benign prostatic hyperplasia.
AB  - Insight into the dysfunctional physiology of benign prostatic hyperplasia has
      expanded appropriate therapies. As the proportion of the population to whom BPH
      will be a problem increases our attention is directed to evolution in clinical
      management.

PMID- 9559248
TI  - Management of impotence in primary care.
AB  - A diversity of successful new therapies for men with impotence dysfunction offers
      renewed optimism about restoration for erectile dysfunction. A minimum of basic
      laboratory investigation, history, and physical is necessary before embarking on
      therapy.

PMID- 9559249
TI  - Lyme disease: diagnosis & management.
AB  - Lyme disease is the most common vector borne illness occurring in the United
      States. Most cases occur in the East. Prompt recognition of typical features and
      understanding the limitations of laboratory testing are essential in order to
      provide appropriate management. Outcome in cases treated early is uniformly good.

PMID- 9559250
TI  - Market consolidation--the key to the future.
AB  - Widespread market consolidation, ongoing changes in Medicare and reimbursement
      schedules, the evolution of managed care. These megatrends have created a
      revolution in the eyecare industry with much instability in the marketplace.
      Practice consolidation on a local level allows practitioners to take charge of
      their destiny.

PMID- 9559251
TI  - A review of the implantable cardioverter defibrillator trials.
AB  - Clinical ventricular tachycardia and ventricular fibrillation are associated with
      a high recurrence rate, and through the 1980s and the early 1990s a variety of
      therapies have been proposed including the implantable cardioverter defibrillator
      (ICD). Over the past decade it has been recognized that prospective randomized
      trials are imperative if the proper role for any therapy is to be defined. The
      Antiarrhythmic Versus Implantable Defibrillator (AVID) trial recently was
      concluded and helped define the role of the ICD in high-risk patients. Other
      trials are studying patients at high risk for sudden death who have not yet had a
      clinical event. The recently concluded Multicenter Automatic Defibrillator
      Implantation Trial and CABG Patch Trial helped determine the proper role of the
      ICD in various pre-event high-risk subsets. These trials are summarized in
      detail.

PMID- 9559252
TI  - Ventricular tachycardia and fibrillation in normal hearts.
AB  - Although ventricular tachyarrhythmias usually occur in the setting of definable
      heart disease, up to 15% of ventricular tachycardias and 10% of ventricular
      fibrillation occur in patients without heart disease. Of the various clinical
      entities comprising these idiopathic ventricular tachyarrhythmias, a few well
      defined clinical syndromes have been described, such as idiopathic right
      ventricular outflow tract tachycardia, idiopathic left posterior fascicular
      ventricular tachycardia, and the right bundle branch block and ST segment
      elevation syndrome of idiopathic ventricular fibrillation. Many advances have
      been made in the past few years in our understanding and treatment of idiopathic
      ventricular tachyarrhythmias, and these advances are the subject of this review.

PMID- 9559253
TI  - Implications and treatment of atrial fibrillation after cardiothoracic surgery.
AB  - Atrial fibrillation (AF) is the most commonly encountered arrhythmia that occurs
      after cardiothoracic surgery. It develops in up to 40% of patients, most
      frequently in the first few postoperative days. The strongest risk factors for AF
      are age and male gender. The pathogenesis of this arrhythmia probably involves
      increased sympathetic activity in the setting of slowed atrial conduction. The
      development of postoperative AF is associated with an increased morbidity, higher
      costs, and prolonged hospitalization. The use of prophylactic beta-blockers and
      procainamide reduces the incidence of AF whereas digoxin, verapamil, and
      amiodarone appear less effective. Once AF occurs, the mainstay of treatment
      remains rate control, anticoagulation, and restoration of sinus rhythm.

PMID- 9559254
TI  - Diagnosis and management of neurocardiogenic syncope.
AB  - The medical term syncope is derived from the Greek word "synkoptein," the
      original meaning of which was "to cut short". Because it is both a symptom and a
      sign, the physician may often find the evaluation of syncope a difficult and
      frustrating endeavor. Over the course of the past decade it has become apparent
      that transient alterations in autonomic nervous system activity, resulting in
      hypotension and bradycardia, are common causes of syncope. At the same time it
      has become apparent that these are a heterogenous group of disorders which, while
      sharing some characteristics, are nonetheless distinct maladies. This article
      attempts to briefly review our current understanding of these disorders and
      suggests guidelines on their diagnosis and management.

PMID- 9559255
TI  - Heart rate variability.
AB  - Heart rate variability is a recognized tool for the estimation of cardiac
      autonomic modulations. Recently, several studies have advanced the field of heart
      rate variability in three areas: 1) in technical modes of electrocardiogram
      processing and heart rate variability assessment, 2) in physiologic understanding
      and interpretation, and 3) in clinical and practical use. The most recent
      technical studies concentrate on the analysis of nonlinear aspects of heart
      period variations and on coherence between electrocardiogram variability and
      other physiologic factors such as respiration. Principal physiologic
      investigations studied the components of heart rate variability attributable to
      the individual limbs of the autonomic nervous system. It is becoming recognized
      that behavior and responses to the environment, including the psychosocial
      environment, play an important role in long-term heart rate variability.
      Established clinical applications of heart rate variability are presently
      restricted to the assessment of risk after myocardial infarction and to the early
      diagnosis of diabetic neuropathy. Nevertheless, recent studies indicate that
      heart rate variability might soon become a similarly powerful tool for risk
      prediction and monitoring of disease progression in congestive heart failure and
      for monitoring or reinnervation after heart transplantation.

PMID- 9559256
TI  - Cardiac pacing in children.
AB  - Indications for cardiac pacing in pediatric patients continue to expand. In
      addition to its traditional use in sinus and atrioventricular nodal disease,
      applications for cardiac pacing now include treatment of tachyarrhythmias after
      repair of congenital heart disease, reduction of left ventricular outflow tract
      obstruction in hypertrophic cardiomyopathy, and prevention of sudden death in the
      congenital long QT syndrome. Whereas many benefits have been well documented in
      adults, they remain anecdotal in children. Programmable features such as rate
      response and antitachycardia pacing contribute to pacemaker versatility and
      facilitate the achievement of normal hemodynamics in children requiring long-term
      pacing therapy.

PMID- 9559257
TI  - New Doppler techniques for the evaluation of regurgitant and shunt volumes.
AB  - The aim of this review is to highlight some relatively new applications of
      Doppler echocardiography in children. Recent observations of flow dynamics
      through a restricted orifice have revealed that flow through an opening converges
      toward the orifice in a series of proximal isovelocity hemispheric surfaces. The
      flow convergence region can be demonstrated by Doppler echocardiography as a
      color mosaic on the ventricular side of the mitral valve in the presence of
      mitral regurgitation and on the left-ventricular side of a ventricular septal
      defect with left-to-right shunting. The continuity principle dictates that
      regurgitant flow rate can be calculated as the product of the hemispheric surface
      area of the flow convergence region and the velocity at that hemispheric surface.
      Using this principle, investigators have made quantitative flow measurements of
      mitral regurgitation, ventricular septal defect flow and aortic regurgitation.
      These studies demonstrate that this new technique of noninvasive quantification
      has the potential of providing direct measures of regurgitant and shunt flow.
      However, further validation in the pediatric population is needed before it can
      be incorporated into routine clinical practice.

PMID- 9559258
TI  - Current therapy of the patent ductus arteriosus.
AB  - The patent ductus arteriosus (PDA) was the first congenital heart lesion to be
      treated surgically and also the first to be treated with nonsurgical catheter
      intervention. Surgical ligation and division of the ductus remains the gold
      standard for consistently achieving complete occlusion. Transaxillary muscle
      sparing thoracotomy and video-assisted thoracoscopic ligation, however, have
      evolved as surgical alternatives with reduced trauma, shorter hospitalization,
      and excellent cosmetic result but are associated with a significant rate of
      residual or recurrent duct patency. With aggressive application of critical
      pathway methods, significant reduction in cost has been achieved for surgical PDA
      closure. Nonsurgical transcatheter closure nevertheless has gained widespread
      acceptance, mostly employing detachable or nondetachable stainless steel coils.
      Coils have superseded the previously popular Rashkind PDA occluder (USCI/Bard,
      Tewksbury, MA) because of significantly lower cost, less cumbersome handling,
      smaller delivery catheters, and superior occlusion rates. Various coil
      implantation techniques and detachment mechanisms have been devised. Large PDAs
      with smallest diameter greater than 5 mm, however, still are better treated
      surgically until appropriate devices become available.

PMID- 9559259
TI  - Interventional therapy for coarctation of the aorta.
AB  - The optimal interventional management of coarctation of the aorta (CoA) remains
      controversial. Although some are strong advocates for surgery, the timing of
      operation in elective cases has been a matter of debate. Among those who advocate
      balloon angioplasty, some recommend dilation only of recurrent CoA. Others
      recommend dilation of native CoA, but only beyond a certain age. Finally, some
      are strong proponents of balloon angioplasty, even in the neonatal period,
      recognizing the need for reintervention (balloon dilation or surgery) in a
      significant proportion of patients. Recent reports suggest similar or slightly
      superior acute results of balloon dilation for native compared with recurrent
      CoA. Balloon-expandable stents are being used increasingly in complex CoAs and in
      failed dilations. A large multicenter study is required to determine the
      respective clinical roles of surgery and balloon dilation in the management of
      CoA.

PMID- 9559261
TI  - Arrhythmias.

PMID- 9559260
TI  - Lung transplantation in children.
AB  - Fewer than 50 pediatric lung transplants are performed each year. Surgical
      advances in the field have resulted in improved operative outcomes and in
      technical innovations that have broadened both the target population and the
      donor pool. At the same time, late referral of critically ill patients and
      shortage of donor organs result in death prior to transplantation for many
      children, and substantial biological barriers exist that prevent achievement of
      satisfactory long-term outcomes for the many who do undergo a successful surgical
      procedure. Until we can better understand and overcome these barriers, lung
      transplantation must be considered a palliative rather than curative procedure.
      In this article, a brief overview of pediatric lung transplantation is offered,
      and contributions to the recent literature are summarized.

PMID- 9559262
TI  - Pediatrics.

PMID- 9559263
TI  - A molecular approach to understanding human sterol metabolism using yeast
      genetics.
AB  - The availability of the sequenced genome of Saccharomyces cerevisiae (yeast) has
      culminated in the use of this model eukaryote to study human diseases at a basic
      level. This article describes the advantages of studying lipid metabolism in this
      genetically facile organism, including examples of conserved functions and
      genetic approaches to identifying new components of cholesterol homeostasis.

PMID- 9559264
TI  - Genetic analysis of hydroxymethylglutaryl-coenzyme A reductase regulated
      degradation.
AB  - Hydroxymethylglutaryl-coenzyme A reductase degradation occurs in the endoplasmic
      reticulum, and is regulated by the mevalonate pathway. In order to discover the
      molecules that mediate the degradation process and its control, we conducted a
      genetic analysis of the degradation of the yeast Hmg2p isozyme of
      hydroxymethylglutaryl-coenzyme A reductase. Hmg2p degradation occurs by the
      action of HRD genes that direct Hmg2p to the ubiquitin-proteasome pathway.
      Regulation of HRD-dependent Hmg2p degradation appears to occur by the action of a
      separate set of CRD genes.

PMID- 9559265
TI  - CaaX converting enzymes.
AB  - Proteins that contain a carboxyl-terminal CaaX motif undergo post-translational
      processing involving prenylation, endoproteolysis and methylesterification. Two
      yeast genes, AFC1 and RCE1, which are candidates for genes encoding CaaX
      converting enzymes, were recently identified. Rce1p is required for the full
      penetrance of the activated Ras2pval19 phenotype in yeast, indicating its
      possible utility as a new target in Ras-based malignancies. Advances in our
      current understanding of CaaX convertases and the functional importance of CaaX
      proteolysis are discussed.

PMID- 9559266
TI  - Expression of large genomic clones in transgenic mice: new insights into
      apolipoprotein B structure, function and regulation.
AB  - Extensive manipulation of the apolipoprotein B gene in yeast and bacterial
      artificial chromosome clones and subsequent expression of these clones in
      transgenic mice have provided fresh insights into several aspects of
      apolipoprotein B biology, including the identification of sequences important for
      lipoprotein (a) assembly, the demonstration that intestinal expression of
      apolipoprotein B is controlled by DNA sequences > 50 kb from the gene, and the
      extraordinary finding that apolipoprotein B is expressed in the heart.

PMID- 9559267
TI  - Two 7 alpha-hydroxylase enzymes in bile acid biosynthesis.
AB  - The addition of a 7-hydroxyl group is an early and often rate-limiting step in
      the synthesis of bile acids. This reaction is catalysed by two cytochrome P450
      enzymes known as cholesterol 7 alpha-hydroxylase and oxysterol 7 alpha
      hydroxylase. cDNAs encoding these proteins have been isolated and used to define
      two evolutionarily conserved pathways that produce 7 alpha-hydroxylated bile
      acids.

PMID- 9559268
TI  - Acyl CoA:cholesterol acyltransferase genes and knockout mice.
AB  - Acyl coenzyme A:cholesterol acyltransferase (ACAT) (EC 2.3.1.26) is an enzyme,
      located in the endoplasmic reticulum of many types of cells, that catalyzes
      cholesterol ester formation from cholesterol and fatty acyl CoA substrates.
      Sterol esterification by ACAT or homologous enzymes is conserved in evolution
      dating back to yeast. The recent cloning of a human cDNA for ACAT, together with
      genome sequencing projects, has led to the identification of an ACAT gene family
      and provided molecular tools for determining ACAT's functions in vivo. Summarized
      here is the current knowledge concerning the molecular genetics of ACAT.

PMID- 9559269
TI  - Roles for the methylation of phosphatidylethanolamine.
AB  - The methylation of phosphatidylethanolamine is an auxiliary pathway for
      phosphatidylcholine biosynthesis in liver. Two forms of the enzyme,
      phosphatidylethanolamine N-methyltransferase, which catalyses this reaction, are
      located on the endoplasmic reticulum and mitochondria-associated membranes. Both
      forms are encoded by a single murine gene, Pempt, located on chromosome 11. The
      expression of the gene begins at birth. An inverse relationship exists between
      the rate of liver growth and the expression of phosphatidylethanolamine N
      methyltransferase. However, disruption of the Pempt gene does not alter liver
      growth in mice or cause any other obvious phenotype.

PMID- 9559270
TI  - Niemann-Pick disease type C.
AB  - Niemann-Pick type C (NPC) is an autosomal recessive lysosomal storage disease.
      Fibroblasts from individuals with Niemann-Pick type C exhibit defective
      intracellular cholesterol transport. Linkage analysis has led to the recent
      cloning of the NPC1 gene on human chromosome 18, which is the major disease
      locus. Analysis of NPC1 reveals homologies with key regulators of cholesterol
      homeostasis and a Drosophila morphogen receptor.

PMID- 9559272
TI  - Update on low density lipoprotein receptor mutations.
AB  - Recent research has focused on the rapid detection of new LDL receptor gene
      variants and large scale screening for known mutations. Whether the nature of the
      mutation in the LDL receptor gene in familial hypercholesterolaemia determines
      clinical variability has been examined, as well as the potential value of
      detecting mutation carriers for clinical practice. There is also evidence that
      some patients with clinical familial hypercholesterolaemia do not have detectable
      defects in the LDL receptor or apolipoprotein B.

PMID- 9559271
TI  - Related membrane domains in proteins of sterol sensing and cell signaling provide
      a glimpse of treasures still buried within the dynamic realm of intracellular
      metabolic regulation.
AB  - Recent discoveries in the regulation of cholesterol metabolism have documented a
      two step proteolytic pathway that regulates nuclear targeting of the sterol
      regulatory element binding proteins. Sterol regulatory element binding protein
      cleavage activating protein is a newly identified protein that modulates the
      proteolytic maturation of the sterol regulatory element binding proteins. It
      contains a domain that is quite similar in sequence to the membrane spanning
      region of the rate controlling enzyme of cholesterol biosynthesis, 3-hydroxy-3
      methylglutaryl coenzyme A reductase. The membrane domain of the reductase is
      involved in its post-translational regulation by cholesterol. The molecular
      defect in the intracellular cholesterol storage disease, Niemann-Pick type C, has
      also recently been identified. Surprisingly, the affected gene encodes a protein
      with similarity to the membrane domains that are conserved in 3-hydroxy-3
      methylglutaryl reductase and sterol regulatory element binding protein cleavage
      activating protein. Furthermore, the cell surface receptor for the sterol
      modified hedgehog morphogen, Patched, also contains a membrane domain with
      significant similarity to this putative sterol monitoring domain. These recent
      developments suggest a common mechanism for sensing intracellular sterol levels
      and cell signaling, which is based on the function of related membrane domains
      that are contained in key regulatory proteins.

PMID- 9559273
TI  - Receptor-associated protein: a specialized chaperone and antagonist for members
      of the LDL receptor gene family.
AB  - Members of the LDL receptor gene family mediate cellular uptake of various
      extracellular ligands, including lipoprotein particles. Ligand interactions with
      these receptors can be antagonized by a 39 kDa receptor-associated protein.
      Recent biochemical, cellular, and genetic studies have shown that receptor
      associated protein is a molecular chaperone/escort protein for LDL receptor
      related protein, a member of the LDL receptor gene family that binds multiple
      ligands. These studies indicate that receptor-associated protein interacts with
      LDL receptor-related protein at multiple sites and assists the proper folding and
      disulfide bond formation of LDL receptor-related protein within the endoplasmic
      reticulum. Following the completion of folding, receptor-associated protein
      remains associated with the receptor during its subsequent trafficking along the
      early secretory pathway, thereby preventing premature ligand interaction with the
      receptor. The ability of receptor-associated protein to universally inhibit
      ligand interactions with members of the LDL receptor gene family underscores the
      use of this protein as a tool in the study of ligand-receptor interactions.

PMID- 9559275
TI  - Nutrition and therapeutics.

PMID- 9559274
TI  - Genetics and molecular biology.

PMID- 9559276
TI  - Genetics and molecular biology.

PMID- 9559277
TI  - Lipid metabolism.

PMID- 9559278
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 9559279
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 9559280
TI  - Therapy and clinical trials.

PMID- 9559281
TI  - Current indications and techniques in evaluating inflammatory disease and
      neoplasia of the sinonasal cavities.
AB  - Imaging strategies of the sinonasal cavities have undergone extensive revision
      over the last 5-year period. The traditional imaging examination of the paranasal
      sinuses, plain film radiography, does reasonably well in diagnosing maxillary,
      frontal, and sphenoid sinusitis. However, it less reliable in depicting
      abnormalities in the ethmoid sinuses, the most common area first affected with
      inflammatory disease. Compared with sinus computed tomography (CT), plain films
      prove to be less specific and sensitive in depicting the extent of sinus
      abnormalities. One series plainly concluded that sinus radiographs were not
      reliable enough to be an integral part of the clinical decision process. The use
      of plain radiographs of the sinuses has clearly been reduced by medical cost
      containment concerns, replacement by superior techniques, and by clear weaknesses
      of the modality. Although it is inexpensive and easily accessible, the low
      sensitivities and inaccuracies of plain film radiography have resulted in the
      current use of CT and high-field-strength (1.5 Tesla) magnetic resonance imaging
      (MRI). By using this cross-sectional imaging, we now visualize directly the
      pathologic conditions within the sinuses, as well as the normal anatomy. We
      discuss current use of diagnostic imaging in the evaluation of patients with
      nasosinusoidal complaints (most commonly resulting from acute and chronic
      inflammatory disease), with complications of sinonasal inflammatory disease, and
      with suspected/documented neoplasia. In addition to developing an imaging
      algorithm to provide the information affecting clinical decision making, we
      detail the specific imaging techniques necessary accurately to obtain that
      information. We also review the specific concerns about imaging patients in the
      intensive care unit and touch on several emerging imaging techniques. The imaging
      workup in pediatric patients and patients with congenital anomalies is beyond the
      scope of this review.

PMID- 9559282
TI  - Measurement of panic disorder by a modified panic diary.
AB  - The psychometric characteristics of panic diary measures were investigated in a
      sample of 37 patients suffering from panic disorder with agoraphobia. Following
      recommendations made in the recent consensus development conference on the
      assessment of panic disorder, daily ratings included not only the occurrence of
      panic attacks but also fear of panic, expectancy of panic, and expected
      aversiveness of panic. These new measures were reliable and, on the whole,
      demonstrated good divergent and convergent validity. Further, adding such
      measures increased the incremental validity of panic disorder assessment.

PMID- 9559283
TI  - Convergent and divergent validity of the Beck Anxiety Inventory for patients with
      panic disorder and agoraphobia.
AB  - Psychometric properties of the Beck Anxiety Inventory (BAI) (Beck and Steer,
      1990) were investigated in a sample of 82 patients suffering from panic disorder
      with agoraphobia. Before and after brief treatment, patients completed a battery
      of questionnaires and, for 2-week periods, kept a daily panic diary in which they
      recorded panic attacks, fear of panic, and average anxiety. The BAI demonstrated
      excellent internal consistency and good test-retest reliability over a 5-week
      interval. A partial multitrait, multimethod correlation matrix provided evidence
      of convergent validity with other measures of anxiety and of divergent validity
      vis a vis measures of depression. Factor analyses of pretest scores and residual
      gain scores used to address criticism that the BAI is excessively panic-centric
      yielded mixed results. In one analysis, the BAI was loaded with multimethod
      measures of panic and anxiety and, in the other, with questionnaire methods of
      assessing anxiety and depression. However, the BAI was clearly distinguished from
      measures of fear of fear, a central construct in panic disorder, and agoraphobic
      avoidance. Finally, the BAI proved sensitive to change with treatment, yielding
      effect sizes for improvement comparable to those of other anxiety measures.

PMID- 9559284
TI  - Panic disorder with smothering symptoms: evidence for increased risk in first
      degree relatives.
AB  - Klein's (1993: Arch Gen Psychiatry 50:306-317) "false suffocation alarm" theory
      of spontaneous panic attacks posits that central receptors compare CO2, O2, and
      lactate levels and trigger panic when an impending "false" state of suffocation
      is detected. Several investigators have found abnormalities of respiratory
      physiology in subjects with panic disorder. Twin and family studies have
      suggested that both panic disorder and tidal volume response to CO2 are
      inherited. We hypothesized that, if smothering symptoms are a marker for a
      hypersensitive suffocation detector and if this hypersensitivity is familial,
      then relatives of panic subjects with smothering symptoms would have higher rates
      of panic with smothering than relatives of panic subjects without smothering. We
      conducted a family study involving 104 panic disorder probands and 247 of their
      interviewed first-degree relatives. Probands and their relatives were interviewed
      using the Schedule for Affective Disorders and Schizophrenia--Lifetime Version
      for Anxiety Disorders to determine their panic disorder and smothering symptom
      status. Relatives of panic probands with smothering symptoms had an almost
      threefold higher risk for panic and an almost sixfold higher risk for panic with
      smothering symptoms when compared with relatives of panic probands without
      smothering. We conclude that panic disorder with smothering symptoms may be a
      subtype of panic disorder associated with increased familial risk and may be a
      group of interest to genetic investigators. These findings provide the first
      empiric evidence from a family study in support of Klein's false suffocation
      alarm theory of spontaneous panics.

PMID- 9559285
TI  - Episodic and chronic obsessive-compulsive disorder.
AB  - Several lines of evidence support the concept of obsessive-compulsive disorder
      (OCD) as a heterogeneous illness. Using a range of factors such as demographic,
      psychosocial, and clinical variables, we compared OCD patients with chronic (n =
      55) versus episodic (n = 46) courses of illness. Patients were evaluated monthly
      for 1 year while receiving no treatment. Significant differences in sex ratio,
      age at onset of the disorder, illness duration, type of symptoms, and familial
      history were found between the two groups. These findings are consistent with the
      concept of OCD as a heterogeneous disorder. Patients with an episodic course of
      the disorder may be a distinct subgroup within the whole group of obsessive
      compulsive patients.

PMID- 9559286
TI  - Cardiovascular and catecholamine response to orthostasis in panic and obsessive
      compulsive disorder and normal controls: effects of anxiety and novelty.
AB  - OBJECTIVE: Studies of the cardiovascular and catecholamine response to
      orthostatic challenge in panic disorder patients have yielded conflicting
      results. Failure to control for the effects of both anxiety and novelty, which
      contribute to subjects' response to orthostatic challenge in control patients,
      could possibly account for this. METHODS: The blood pressure, pulse, plasma
      norepinephrine and epinephrine responses to orthostasis were examined in patients
      with panic disorder, obsessive-compulsive disorder (to control for nonspecific
      anxiety effects), and controls, on two separate days a week apart (to control for
      novelty). RESULTS: All measures showed robust and significant increases with
      orthostatic challenge that were generally similar across groups. Pressure
      responses were greater on average on the first compared with the second day and
      panic disorder patients had higher plasma norepinephrine levels throughout the
      study and a diminished diastolic blood pressure response on the first day.
      CONCLUSIONS: These findings in general support the absence of consistent
      peripheral autonomic nervous system differences in response to orthostatic
      challenge in panic disorder patients.

PMID- 9559287
TI  - Course of obsessive-compulsive symptoms in Tourette's syndrome.

PMID- 9559288
TI  - Open-label pilot study of tramadol hydrochloride in treatment-refractory
      obsessive-compulsive disorder.

PMID- 9559289
TI  - Intratumoral genetic heterogeneity in primary head and neck squamous carcinoma
      using microsatellite markers.
AB  - We investigated intratumoral genetic variability using 13 of the most frequently
      altered microsatellite loci in primary head and neck squamous carcinoma to
      determine the extent and the implication of this feature on the interpretation of
      the genetic analysis of these tumors. DNA extracted from four spatially different
      samples of 17 prospectively resected specimens, in addition to matching normal
      mucosa, was tested. Overall, the highest incidence of loss of heterozygosity was
      noted at chromosomes 3p and 9p loci (70% in each). Chromosomes 8p and 17p loci
      showed 35% and 40% loss of heterozygosity, respectively. Loss of heterozygosity
      was homogeneously manifested in all different samples of tumors with these
      alterations. Microsatellite instability was noted in two (17%) tumors, one of
      which showed intratumoral heterogeneity. Our study indicates that single sample
      analysis may reflect the genetic alterations in a given primary head and neck
      squamous carcinoma using these markers.

PMID- 9559290
TI  - Renal primitive neuroectodermal tumor: a morphologic, cytogenetic, and molecular
      analysis with the establishment of two cultured cell lines.
AB  - We report two patients with renal primitive neuroectodermal tumor (PNET) in whom
      the diagnosis was established by both a cytogenetic and a molecular analysis.
      Histologically, both renal tumors were composed of uniform immature round cells
      with a positive immunoreactivity for O13 (p30/32 MIC2). The cytogenetic analysis
      with in situ hybridization (chromosome painting) demonstrated reciprocal
      translocation t(11;22)(q24;q12) specific to PNET in the cultured cells derived
      from each tumor. The reverse transcriptase-polymerase chain reaction (RT-PCR) in
      both tumors demonstrated EWS/ FLI-1 fusion transcripts, representing the
      molecular equivalent of t(11;22). A Southern blot analysis also confirmed EWS
      gene rearrangement in both renal tumors. In addition, the authors also
      established two new cell lines (designated as FU-RPNT-1 and FU-RPNT-2) from renal
      PNETs. When transplanted into athymic mice, FU-RPNT-1 and FU-RPNT-2 reproduced
      and maintained the morphologic and molecular characteristics of the original
      tumors. In conclusion, the detection of t(11;22) and EWS/FLI-1 fusion transcripts
      is considered to provide a novel adjunctive method for diagnosing renal PNET.
      These newly established cell lines thus may be used to investigate the biologic
      behavior related to renal PNETs.

PMID- 9559291
TI  - Comparison of genetic changes in frozen biopsies and microdissected archival
      material from the same colorectal liver metastases.
AB  - Microdissection of tissue sections from formalin-fixed, paraffin-embedded tumor
      material allows separation of microscopic sites within a sample. DNA can easily
      be extracted, and polymerase chain reaction (PCR) technology makes it possible to
      perform different molecular biologic analyses on small cell populations. The
      presence of normal cells or tumor heterogeneity may cause false negatives in
      allelic imbalance (AI) studies. Microdissected well-defined cell populations from
      a tumor section are assumed to increase the sensitivity of AI analyses. The
      present study has evaluated this in colorectal liver metastases by comparing
      genotypes in frozen biopsies with genotypes in microdissected archival samples
      from the same patients. Constitutional genotypes were obtained from corresponding
      peripheral blood leukocytes as well as normal liver tissue. Archival samples (n =
      43) from 16 patients were analyzed after microdissection with 2-5 of 10 selected
      microsatellite markers. Frozen biopsies from one metastasis of each patient had
      previously been investigated at numerous microsatellite loci. From those results
      we selected, for the comparable analysis of archival samples, 41 tumor genotypes
      at 10 loci representing 11 heterozygotes, 13 AI, 7 losses of heterozygosity
      (LOHs), 8 homozygotes, and 2 microsatellite unstable cases. The microdissected
      samples revealed AI or a complete loss of one allele (LOH) in 5 of 11 (45%)
      genotypes that were previously evaluated as unchanged (retained heterozygosity)
      in the frozen biopsies, and LOH in 8 of 13 (62%) genotypes at loci known to
      exhibit AI in the frozen biopsies. Microsatellite instability, LOH, and
      homozygosity found in the frozen samples were all confirmed by analyses of the
      archival material. Intertumoral genetic heterogeneity was found in samples from
      two patients. The same allelic intensities were seen in DNA from tumor-close
      liver tissue as in blood DNA from the same patient except in one sample. The
      present study shows a 54% increase in sensitivity of genetic alterations if pure
      tumor cell components are used (five "new" AIs and LOHs and eight "new" LOHs
      among previously scored heterozygotes [n = 11] and AI [n = 13], respectively). In
      total, a 93% success rate (108/115 analyses) was obtained using standard PCR
      conditions for the 10 selected markers. The fact that standard PCR conditions and
      5-micron tumor sections are used shows how easy these analyses are to perform,
      and that only minor amounts of valuable archival material is used.

PMID- 9559292
TI  - Gene expression of malignant rhabdoid tumor cell lines by reverse transcriptase
      polymerase chain reaction.
AB  - Malignant rhabdoid tumors (MRT) are characterized by unique neoplastic cells
      demonstrating phenotypic diversity. By using the reverse transcriptase-polymerase
      chain reaction, we have detected expression of various genes before and after
      differentiation induction with four different agents in four established MRT cell
      lines (TM87-16, STM91-01, TTC642, and TTC549). The agents used in this study were
      all-trans retinoic acid (RA), 12-O-tetradecanoylphorbol-13-acetate (TPA),
      interleukin-3, or interferon-gamma. Before and after induction, c-myc, IGF-II,
      IGF-I receptor, and IGF-II receptor were constitutively expressed by all four
      cell lines. The neurofilament medium-size (NF-M) was constitutively expressed by
      the TM87-16 and TTC642, and the S100 protein alpha subunit was expressed by TM87
      16, TTC642, and TTC549. Chromogranin A was expressed by TM87-16 only after
      treatment with either TPA or RA. MyoD, N-myc, tyrosine hydroxylase, N-CAM, trkA,
      and the S100 protein beta subunit were not expressed by any cell line before or
      after induction with these agents. All the MRT cell lines in this study except
      TM87-16 were highly resistant to differentiation induction. The proliferating
      cells in TM87-16 and TTC642 expressed mRNA profiles characteristic of
      neuroectoderm.

PMID- 9559294
TI  - DNA extraction from formalin-fixed, paraffin-embedded tissues: protein digestion
      as a limiting step for retrieval of high-quality DNA.
AB  - Several DNA extraction methods have been used for formalin-fixed, paraffin
      embedded tissues, with variable results being reported regarding the suitability
      of DNA obtained from such sources to serve as template in polymerase chain
      reaction (PCR)-based genetic analyses. We present a method routinely used for
      archival material in our laboratory that reliably yields DNA of sufficient
      quality for PCR studies. This method is based on extended proteinase K digestion
      (250 micrograms/ml in an EDTA-free calcium-containing buffer supplemented with
      mussel glycogen) followed by phenol-chloroform extraction. Agarose gel
      electrophoresis of both digestion buffer aliquots and PCR amplification of the
      beta-globin gene tested the suitability of the retrieved DNA for PCR
      amplification.

PMID- 9559293
TI  - Molecular alterations of the RB1, TP53, and MDM2 genes in primary and xenografted
      human osteosarcomas.
AB  - We report the status of the RB1, TP53, and MDM2 genes in human osteosarcomas and
      cell lines established from surgical specimens and transplanted into athymic
      naked mice. By using reverse transcriptase-polymerase chain reaction (RT-PCR) as
      a prescreening technique and posterior sequencing, we observe new mutations in
      the RB1 gene, notably a duplication in tandem of exons 3 through 6. TP53
      mutations appear in codons most frequently mutated in osteosarcomas. We have not
      seen MDM2 gene amplification in any reported case. These molecular alterations
      appear in different osteosarcomas not simultaneously present in the same tumor
      sample. A link has been described between these three genes in the pathways that
      control the cell cycle and the tumoral progression, but their functions are
      probably independent in the development of osteosarcomas. TP53 mutations appear
      in adult patients, whereas RB1 alterations occur mostly in younger patients.

PMID- 9559295
TI  - A microplate allele-specific oligonucleotide hybridization assay for detection of
      factor V Leiden.
AB  - Factor V Leiden is the most common genetic risk factor for thrombosis. Currently,
      the determination of factor V Leiden genotype is limited to laboratories with
      expertise in molecular methods to develop "home brew" assays using polymerase
      chain reaction (PCR) to amplify genomic DNA, followed by analysis of Mnl I
      restriction fragments. These methods are not standardized, are labor intensive,
      and have low throughput. We describe a method for determination of factor V
      Leiden genotype using allele-specific oligonucleotide capture probes coated onto
      96 well plates, requiring only a thermal cycler and a microplate
      spectrophotometer to perform. With an automated strip washer and plate reader,
      genotypes could be determined in 80 min from completion of PCR. Within-run and
      between-run coefficients of variation for the assay were < 10%. In all 160 cases
      studied, the microplate assay correctly identified the factor V genotype. The
      microplate oligonucleotide hybridization assay is a simple and reliable system
      for determination of factor V Leiden genotype. The assay offers an automatable,
      high-throughput alternative to current testing methodologies.

PMID- 9559296
TI  - A method to monitor mRNA levels in human breast tumor cells obtained by fine
      needle aspiration.
AB  - A method based on the reverse transcriptase-polymerase chain reaction (RT-PCR)
      was developed that allows the determination of relative mRNA expression levels in
      fine-needle aspirates from human tumors. The method was developed for the c-erbB
      2 gene, using the porphobilinogen deaminase (PBGD) gene as an internal standard.
      It was validated for mRNA isolated from cell lines and for material obtained by
      fine-needle aspiration from human breast cancer. Gene expression levels were
      determined by measuring the activity of radiolabeled RT-PCR-amplified gene
      specific bands with a phosphor imager. At least four points are measured on the
      log-linear part of the amplification cycle versus signal intensity curves, and
      subsequently the distance between the curves of the gene of interest and that of
      an internal standard gene is used to calculate the relative expression levels.
      The method worked equally well with the BRCA1 gene, illustrating that it can be
      generalized to other genes. The method is suitable to measure or monitor
      semiquantitively gene expression levels in accessible human tumors in situ.

PMID- 9559297
TI  - [Adverse seizure reactions after electroconvulsive therapy. Study of personal
      cases and review of the literature].
AB  - OBJECTIVE: To determine what are the risk factors for the occurrence of unwanted
      seizures after an ECT session, and what is the best attitude regarding future
      ECT. METHOD: We have reviewed all the case reports published in the literature
      between 1946 and 1995 and have carried out a prospective case-control study of
      all incidental seizure type side effects among a group of 43 patients treated
      consecutively using the same procedure within the same institution in 1993.
      RESULTS: Results from the literature are presented in tables I to IV and results
      from our case-control study in tables V to VIII. Twenty seven seizure type side
      effects are reported in 22 published papers reporting the case of 24 patients.
      Most accidents occur during the first ECT and the occurrence of non convulsive
      seizures is greatly increased in case of coexisting EEG-monitoring. In our own
      study the overall incidence is 0.95%. Risk factors are neurologic disease,
      psychotropic medication, history of prolonged seizure during previous ECT.
      CONCLUSION: It appears that no unique risk factor but a summation of several
      risks (personal or family history of seizure, psychotropic medications, high
      energy level of electric stimuli) for specific subjects increases the risk for
      seizures after ECT. ECT can be resumed if necessary after occurrence of a post
      ECT seizure with addition of anti-epileptic medication.

PMID- 9559298
TI  - [Evaluation of the quality of life of chronic psychotic patients living in
      supportive housing].
AB  - This study concerns 46 chronically mentally ill patients living in community
      support systems. Their quality of life was measured with a validated
      questionnaire: the "Subjective Quality of Life Questionnaire" ("SQLP"). Both
      patients and their care givers separately completed the same version of the
      questionnaire. This study first shows the feasibility of such inquiries with
      chronically mentally ill patients. It gives a description of the patient's
      feeling which is different from the usual medical point of view. The life domains
      the patient is very satisfied with are mostly restricted to food, material
      conditions, and relationship with the care-givers, but exclude the other
      relationships. Our data also allow to estimate the degree of agreement and
      disagreement between the care-givers and their patients.

PMID- 9559299
TI  - [Psychiatric emergency department of the Pinel hospital center].
AB  - According to objective expressed by 1992's decree about psychiatric's emergency,
      Philippe Pinel's hospital in Amiens have emergency ward since march 1994.
      Computing activity within hospital allow to surround characteristics of patients
      who come to psychiatric's hospital emergency, 2,122 patients have been examined
      in 1995, either 6 a day. 220 were consultations, 1,920 were admittance to
      hospital. Among these 2,122 patients, 20.5% don't know mental hospital, 19% don't
      know psychiatry, 40% have a relapse and 20% where hospitalized but without met
      again a doctor. On the average, one hour was dedicated to patient in 1995. On a
      level with sociocultural, men are 59%, which 26% between 30 and 39 years, and 25%
      between 40 and 49 years. Among the patients, 69% live alone, and 12% have social
      difficulty. Patients are sent by General Hospital (27%), general practitioners
      (24%, but this number grow in 1996), and various psychiatric institutions (10%).
      The main symptoms are: sadness and depression (40%), anxiety (37%), sleep
      disruption (31%), alcoholism (23%), bodily symptoms (16%), attempt to suicide
      (15%), social problems (14%). After observation, diagnosis are: psychosis (30%),
      neurosis (23%), alcoholism (19%), "anti-social" personality (10%), and drug
      addiction (7%). Among these 2,122 patients in 1995, 90.5% (1920) are sent to
      hospital, which 72% with their assent, and 28% under constraint. Consultations
      (9.5%) are sent to psychiatric's institution (43%), general hospital (35%), and
      psychiatrist (6%). In conclusion, computing activity within psychiatric's
      emergency could enable best reception, guidance, and collaboration with social or
      medical colleague.

PMID- 9559300
TI  - [Is the functioning of our brain of an addictive nature?].
AB  - The concept of addiction is increasingly bound to a general model of
      heterogeneous and polymorphous dependences. In this paper we examine upstream
      what could found this universal addictive principle, asking the question of the
      neurobiological root of addictivity. In other words, is the root of our brain
      working in an addictive way? To answer affirmatively to this question we gather
      two sets of datas: firstly, the conditions of the brain addictivity and secondly,
      the brain mechanisms that suggest this kind of addictive working. These datas are
      common if we consider them one by one, but their synthesis in a bundle of
      heuristic clues could be interesting to examine and to submit to thought. The
      model we suggest proposes that the architecture of our brain and the type of
      functioning of our neurones, imply the presence of a natural addictive set of
      problems in all human beings, between a fight against cerebral background noise-
      a dysphoric source--and a stimulation need. Finally, considering some
      neurobiological data in the last five years, we propose a triangular model of the
      addict brain, that involves three associated systems: "arousal" system, "liking"
      system and "wanting" system. This model, supported by the sensation seeking one,
      will allow us to suggest an explanation of the processes that lead to
      pathological addictions, according to the principles of a natural and universal
      addictivity.

PMID- 9559301
TI  - [Validation of the French version of the revised Personal Style Inventory
      (revised Personal Style Inventory, PSI-II, Robins et al., 1994)].
AB  - The aim of the present study is to determine the validity and reliability of the
      French version of the PSI-II. The PSI-II is a self-rating scale divided into two
      subscales containing each 24 items and rating sociotropy and autonomy. 202
      university students (170 females, 32 males) with a mean age of 21.54 years (sd =
      4.16) were included. They filled out the PSI-II and the Interpersonal Dependency
      Inventory (IDI). The construct validity was explored using an exploratory
      principal components analysis followed by an orthogonal varimax rotation. The
      results had shown a three-factor solution with a "sociotropy" factor and two
      "autonomy" factors. The Cronbach alpha coefficients were respectively 0.83 and
      0.72 for the sociotropy and autonomy subscales. The Pearson correlations between
      the PSI-II and IDI subscales showed significant correlation first between the
      sociotropy subscale and the two subscales of the IDI rating dependency, the
      values were respectively 0.67 (p < 0.001) and 0.44 (p < 0.001), and secondly
      between the autonomy subscales of the PSI-II and IDI, the value was 0.39 (p <
      0.001). The sociotropy subscale items correlated significantly with the total
      score of the subscale with a mean of 0.46. 23 items of the autonomy subscale
      correlated with the total score with a mean of 0.36. The sociotropy and autonomy
      scores were respectively 93.98 (sd = 14.22) and 84.55 (sd = 11.69). The French
      version of the PSI-II had satisfactory metrological parameters and allows to
      study sociotropy and autonomy in French population.

PMID- 9559302
TI  - [Tridimensional Personality Questionnaire (TPQ): validation in a French-speaking
      control population].
AB  - Among the dimensional scales that measure personality, Cloninger's TPQ
      (Tridimensional Personality Questionnaire) holds a place apart in the literature,
      because the hypotheses it relies on are partially biological. The questionnaire
      (100 forced binary items) includes three axes: "Novelty Seeking", "Harm
      Avoidance" and "Reward Dependence", each theoretically bound to a preferential
      neuromediator, respectively dopamine, serotonin and norepinephrine. Each axis
      includes four minor subscales. The study presented here is the analysis of 104
      control volunteers from both genders (59 males). This database is the first to be
      published with a French-speaking population. The comparison with Cloninger's
      normative database shows many similarities: the mean values for the 3 axes are
      relatively close. The population studied here is younger and this factor could
      play a role in the somewhat higher mean novelty seeking scores found here. The
      three axes show a normal distribution. Skewness and kurtosis are between -1 and
      +1 for all the subscales, except here for NS2. Factorial structure is quite
      similar to Cloninger's results. The three first axes correspond to the variables
      isolated in the first studies and the fourth one includes the same subscales as
      in the large American database. Inverse correlation between age and novelty
      seeking, positive correlation between female gender and harm avoidance and reward
      dependence were also found. However, no correlation was found between novelty
      seeking and male gender. A correlation was found between level of instruction and
      NS1 only, not with the whole NS axis. Eighty-seven % of volunteers presented with
      at least one standard deviation on at least one axis and 68% on at least two.
      This does not seem to have been described previously. It can be a sign of the
      difficulty of human beings to show a balanced personality. In conclusion, the
      database presented here shows many similarities with Cloninger's normative
      database. This underscores its value for comparisons in clinical trials in the
      future.

PMID- 9559303
TI  - [Bulimia and autoimmunity].
AB  - In the first part of this study, we investigated the rate of natural
      autoantibodies, in a sample of 31 female inpatients with bulimia nervosa
      according to DSM III-R criteria. The control (age and sex matched) group
      consisted in high school students including 10 females without eating disorders,
      depressive disorder or immunological disease. We investigated especially natural
      autoantibodies reacting with compounds of the central nervous system (Dopamine,
      Dopamine beta Hydroxylase, Serotonin). Our first conclusion is that there is a
      lower level of these natural auto-antibodies among female patients with bulimia
      nervosa. In the second part of the study, we have especially investigated the
      correlation between impulsivity in bulimia nervosa and the rate of natural
      autoantibodies against serotonin.

PMID- 9559305
TI  - [Fluoxetine: relations between plasma concentration and therapeutic effects in 32
      patients with major depression and treated with 20 mg/day].
AB  - The aim of this clinical study was to investigate 32 melancholic patients treated
      by fluoxetine (20 mg/day). The clinical examination to evaluate the
      antidepressant effect of fluoxetine was realized by using the HDS/MES criteria.
      The patients were divided into three groups (responders, partial responders with
      or without a relapse, non responders) according to their clinical evolution
      during treatment. Fluoxetine and norfluoxetine were evaluated by HPLC after 3
      weeks of treatment. In the present study, 53% of the patients have a positively
      reaction to the 21 day's treatment. Our results showed no correlation between the
      psychiatric scores and the plasma concentrations of fluoxetine and norfluoxetine.

PMID- 9559304
TI  - [Absence of frontal lobe dysfunction and working memory deficits in young
      schizophrenic patients].
AB  - The impairment in tasks requiring intact frontal lobe functions has been
      repeatedly shown in schizophrenics. However, the relative roles of confounding
      factors, like duration of the disease, social withdrawal, or antidopaminergic
      medication, are not clearly demonstrated. We studied the performance of 12 young
      active patients, with chronic residual schizophrenia that had recent onset, and
      12 control subjects, with frontal lobe tests and with a battery designed to
      explore working memory. The results show normal performance in schizophrenia. The
      small number of patients does not allow definitive conclusions, but this study
      suggests that a frontal dysfunction may not be present early in the evolution of
      schizophrenia in active patients.

PMID- 9559306
TI  - [Secondary dermatologic effects of serotonin reuptake inhibitor antidepressants:
      hypothesis of cross-reacting allergy. Apropos of 2 cases].
AB  - Toxidermia is a well-known complication of antidepressant therapy. The authors
      report two cases of adverse cutaneous reactions after treatment by several
      serotonin uptake blockers. The first case concerns a 38-year-old woman, who
      suffered from depressive disorder. She has been treated with fluoxetine. After
      eight days, a cutaneous reaction appeared. This reaction subsided when fluoxetine
      was stopped. Two months later, she had a prescription of paroxetine, and the same
      skin adverse effect appeared. The cutaneous lesion decreased with the suppression
      of paroxetine. The chronology of the eruption suggests that it was caused by an
      adverse reaction to the both serotonin uptake blockers. The second case concerns
      a 40-year-old man who had several prescriptions of antidepressant treatment in a
      period of one year: fluoxetine, fluvoxamine, paroxetine and sertraline. Each time
      a cutaneous reaction appeared. It is advisable to substitute after an adverse
      effect a medication from one of the other classes of antidepressants. But what we
      saw in these cases is that the serotonin uptake blockers could be involved in the
      same allergic reaction while these drugs have different chemistry structures.
      Only three of them have the same excipient. These cases ask the question of cross
      reactivity between the serotonin uptake blockers.

PMID- 9559307
TI  - [Psychiatric manifestations as the only clinical sign of hypothyroidism. Apropos
      of a case].
AB  - This article intends to demonstrate, by presenting a clinical case, the
      importance of the thyroid examination in psychiatric practice. After a brief
      presentation of the evolution of the conceptions regarding the relation between
      thyroid insufficiency and psychiatric pathology, a clinical case is reported.
      This 63 years old man was admitted in a psychiatric ward because of his
      persecutive delusions and behavioral disorders (agitation, agressivity).
      Cognitive (namely memory) impairment was also present at the time of admission.
      The endocrine investigation has documented, in spite of the absence of any
      suggestive physical signs, a thyroid insufficiency. After the replacement
      treatment, all symptoms but the cognitive dysfunction disappeared. The patient's
      evolution is presented clinically, also rated on MMSE and MADRS scales, and
      biologically (TSH and T4 determination) for a 4 months period. The absence of any
      pathognomonical psychiatric finding, the possibility of the absence of other
      signs and symptoms (namely physical) in the hypothyroid state, the presence of
      potentially irreversible cognitive deterioration, as well as the inocuity and
      sensibility of thyroid hormones examination justify the systematic thyroid
      evaluation for all new psychiatric patients.

PMID- 9559308
TI  - [Apropos of specific psychiatric disorders in men].

PMID- 9559309
TI  - Regulation of keratinocyte proliferation.
AB  - 1. In physiological situations the proliferation of epidermal cells
      (keratinocytes) in the skin is a tightly controlled process. 2. However, in many
      common skin diseases, such as in psoriasis, the control mechanisms go awry
      resulting in pathological epidermal hyperplasia (thickening). 3. In those
      situations the keratinocytes enter the alternative pathway of proliferation
      characterized by excessive growth rate, aberrant responses to growth factors,
      faulty differentiation, and increased migratory capacity. 4. The participation of
      different growth factors in enhancing or inhibiting keratinocyte growth, both in
      physiological and pathological conditions, has been reviewed. 5. The regulatory
      processes governing epidermal growth have relevance for the understanding of the
      mechanism of action of the drugs used in the treatment of skin diseases
      associated with epidermal hyperplasia.

PMID- 9559310
TI  - Tumor resistance to antimetabolites.
AB  - 1. The inherent or acquired resistance of certain tumors to cytotoxic drug
      therapy is a major clinical problem. 2. Resistance to the chemotherapeutic
      antimetabolites (e.g., methotrexate, 5-fluorouracil, tomudex and gemcitabine) is
      no exception. 3. Mechanisms of resistance include mutations, amplification of
      target genes, altered drug transport, differences in nucleoside and nucleobase
      salvage pathways, DNA damage-response pathways and cell cycle control pathways.

PMID- 9559311
TI  - Antioxidant and pharmacodynamic effects of pyridoindole stobadine.
AB  - 1. The review summarizes the most important data known so far on chemistry,
      pharmacodynamics, toxicology and clinics of the investigational agent,
      pyridoindole stobadine. 2. Stobadine was shown to be able to scavenge hydroxyl,
      peroxyl and alkoxyl radicals, to quench singlet oxygen, to repair oxidized amino
      acids and to preserve oxidation of SH groups by one-electron donation. These
      effects originated from its ability to form a stable nitrogen-centered radical on
      indole nitrogen. Consequently, it was able to diminish lipid peroxidation and
      protein impairment under oxidative stress. 3. In various in vitro and in vivo
      animal models, stobadine was shown to diminish the impairment of the myocardium
      induced by mechanisms involving reactive oxygen species (e.g., myocardial
      infarction, hypoxia/ reoxygenation, catecholamine overexposure). 4. The
      neuroprotective effect of stobadine was demonstrated in a series of in vivo and
      in vitro models (brain in situ, brain slices, spinal cord, autonomic ganglia,
      etc.) during ischemia/reperfusion and hypoxia/ reoxygenation or in the presence
      of chemical systems generating free oxygen radicals, and so forth. Stobadine
      improved animal survival rate and synaptic transmission recovery, maintained SH
      tissue level and diminished lipid peroxidation as well as impairment of Ca
      sequestering intracellular systems. 5. Oxidation of low-density lipoproteins
      (LDLs), which plays a major role in the development of atherosclerosis, was
      decreased by stobadine in vitro. Both lipid and protein (apo B) components of LDL
      were protected against Cu(2+)-induced oxidation by this agent. 6. Stobadine
      proved to be an effective protectant in models of free radical pathology in vivo,
      such as cyclophosphamide-, MNNG- or 60Co-induced mutagenesis and alloxan-induced
      hyperglycemia. 7. Besides other remarkable pharmacodynamic effects, stobadine
      exerts antidysrhythmic, local anesthetic, alpha-adrenolytic, antihistaminic,
      myorelaxant and antiulcerogenic actions. 8. Pharmacokinetic analyses demonstrated
      that stobadine was readily absorbed from the gastrointestinal tract. Thanks to
      its balanced lipo-hydrophilic properties, it was distributed over both water and
      lipid phases in biological tissues. It was shown to easily penetrate the blood
      brain barrier. 9. Acute, subchronic and chronic toxicity studies in several
      animal species, as well as numerous analyses of embryotoxicity, teratogenicity,
      mutagenicity and genotoxicity, revealed only a negligible toxic potential of this
      agent. 10. Phase-one clinical study demonstrated safety of the compound. Only
      slight side effects--namely, a slight hypotension and a slight sedative effect-
      were observed subsequent to the highest dose used. In phase-two clinical study,
      the patients with angina pectoris treated for 4 weeks with stobadine showed a
      significant decrease in the frequency of anginal attacks, in the number of self
      administrations of sublingual nitroglycerine and in plasma lipoprotein,
      cholesterol and triglyceride levels. A slight decrease in systolic and diastolic
      blood pressure also was observed. 11. It is suggested that stobadine may be
      considered a contribution to the search for new effective cardio- and
      neuroprotectants based on antioxidant or free radical scavenging mechanisms of
      action.

PMID- 9559312
TI  - Ranolazine: a novel metabolic modulator for the treatment of angina.
AB  - 1. Ranolazine shifts ATP production away from fatty acid oxidation toward glucose
      oxidation. 2. Because more oxygen is required to phosphorylate a given amount of
      ATP during fatty acid oxidation than during carbohydrate oxidation, the
      ranolazine-induced shift in substrate selection reduces the cell's demand for
      oxygen without decreasing its ability to do work. The shift also maintains
      coupling of glycolysis to glucose oxidation during ischemia, thus reducing tissue
      acidosis. 3. This unique, non-hemodynamic mechanism offers the potential to treat
      angina without reducing blood pressure, heart rate or myocardial contractility.
      4. At least three double-blind, randomized, placebo-controlled clinical trials
      have yielded data consistent with this hypothesis.

PMID- 9559313
TI  - Fetal digoxin treatment enhances the binding capacity of thymic glucocorticoid
      receptors in adult female rats.
AB  - 1. Hormonal imprinting is provoked in the perinatal critical period in the
      presence of the appropriate hormone or molecules similar to it. As a consequence
      of hormonal imprinting, the developing receptor finishes its maturation normally
      (in the presence of the adequate hormone) or abnormally (under the effect of
      foreign molecules that are able to bind to the receptor). 2. Digoxin--which has a
      steroid character--caused faulty imprinting by treatments at the 15th, 17th and
      20th days of pregnancy. In the adult (3-month-old) animals, the density of thymic
      glucocorticoid receptors was significantly elevated, whereas the density of
      uterine estrogen receptors was not, without any change in receptor affinity. 3.
      The experiments call attention to the steroid receptor imprinting effect of fetal
      digoxin treatment that must be considered in regard to this treatment at this
      period and later in regard steroid treatments.

PMID- 9559314
TI  - Vasodilatation induced by nicotine in the isolated perfused rat kidney.
AB  - 1. In isolated perfused rat kidney, under a constant flow of 8-10 ml/min, mean
      basal perfusion pressure was found to be 82.57 +/- 8.96 mm Hg (n = 70). 2. After
      a bolus injection of 10 micrograms/0.1 ml phenylephrine (PE) which causes maximum
      vasopressor response, a 93.27 +/- 0.56 mm Hg increase in basal perfusion pressure
      was recorded (n = 70). In control experiments, a submaximum dose of PE (3 x 10(
      6) M) caused a 68.37 +/- 0.47 mm Hg (n = 5) increase in perfusion pressure. 3.
      Nicotine, at a dose of 100 micrograms/0.1 ml, decreased the perfusion pressure
      raised by submaximum dose of PE. This nicotine-induced dilatation was 24.97 +/-
      3.27% of maximum PE constriction (n = 5). 4. Nicotine-induced dilatation was not
      affected by atropine, guanethidine, hexamethonium, tetrodotoxin, capsaicin,
      indomethacin, quinacrine, NG-nitro-L-arginine, methylene blue, glibenclamide,
      tetraethylammonium, 4-aminopyridine and ouabain (n = 5).

PMID- 9559315
TI  - The influence of Ca2+ on the effects of glucagon on hepatic glycolysis.
AB  - 1. The influence of Ca2+ on the effects of glucagon on glycolysis was
      investigated in the isolated perfused rat liver. Livers from fed rats were
      perfused in an open system with Krebs/Henseleit-bicarbonate buffer (pH 7.4).
      Glucose release, lactate plus pyruvate production (glycolysis) and oxygen uptake
      were measured. The following results were obtained: 2. In livers perfused with
      Ca(2+)-free Krebs/Henseleit-bicarbonate buffer and after depletion of the
      intracellular pools, the initial and transient stimulation of glycolysis, which
      is normally observed shortly after the onset of glucagon infusion, was more
      pronounced when compared to livers perfused with normal perfusion fluid (2.5 mM
      Ca2+) and without previous depletion of the intracellular pools (controls); the
      subsequent inhibition of glycolysis was delayed in Ca(2+)-free perfused livers
      and was less pronounced in comparison with the controls at the end of the
      glucagon infusion period (20 min). 3. Perfusion with a Ca(2+)-free medium
      supplemented with EDTA, without previous depletion of the intracellular pools,
      also produced a substantial reduction in the effects of glucagon on glycolysis.
      4. Ca(2+)-free perfusion did not affect the stimulative action of glucagon on
      glucose release (glycogenolysis) and oxygen uptake. 5. Glycolysis inhibition by
      cAMP also was abolished in Ca(2+)-free perfused livers, and the initial
      stimulation was enhanced. 6. Mn2+, a metal ion known as a competitor of Ca2+,
      considerably reduced the action of glucagon on glycolysis; Mn2+ did not affect
      the basal rates of glycolysis. 7. Sr2+, a metal ion that is often recognized as
      Ca2+ by several biological structures and processes, increased the inhibitory
      action of glucagon on glycolysis. 8. Several organic compounds, which directly or
      indirectly take part in Ca2+ fluxes, were also able to diminish (e.g., verapamil)
      or even to abolish (carbenoxolone) the inhibitory action of glucagon on
      glycolysis. 9. It was concluded that, under the conditions of the living cell,
      Ca2+ is important for glycolysis inhibition by glucagon. In principle at least,
      the results can be explained in terms of the known Ca2+ dependencies of several
      protein kinases and protein phosphatases.

PMID- 9559316
TI  - Acute and chronic effect of ethanol on (Na + K)-ATPase activity and cyclic AMP
      response to vasopressin in rat papillary collecting duct cells.
AB  - 1. We evaluated the effects of ethanol on (Na + K)-ATPase activity and cAMP
      response to vasopressin in native and cultured rat papillary collecting duct
      (PCD) cells. 2. A significant increase in (Na + K)-ATPase and Mg(2+)-ATPase
      activities was found in PCD cells either isolated from chronic ethanol-fed rats
      or cultured in the presence of ethanol. 3. Acute treatment with ethanol resulted
      in a biphasic effect on the activity of (Na + K)-ATPase, which was enhanced below
      1% ethanol and inhibited at higher concentrations. 4. Chronic ethanol treatment
      did not change the cAMP response of PCD cells to vasopressin. Acutely, in turn,
      this response was enhanced by ethanol per se. 5. It is suggested that the
      antinatriuretic effect of ethanol could be at least in part mediated by a (Na +
      K)-ATPase enhancement in PCD cells. Acutely, ethanol could normalize water
      balance by its peripheral effects on distal nephron.

PMID- 9559317
TI  - Effects of d-amphetamine on the frequency of the spontaneous contraction of the
      portal vein in rat.
AB  - 1. Effects of d-amphetamine on the frequency of spontaneous contraction of the
      longitudinal muscle of the portal vein were studied in Wistar rats. Its effects
      on the circular muscles of the pulmonary artery and stomach also were tested. 2.
      d-Amphetamine increased the frequency of the spontaneous contraction of the
      portal vein. The ratio of the frequency of the spontaneous contraction of the
      portal vein before and after d-amphetamine treatment also was increased. The
      effect was not affected in the presence of prazocin, (+)-lysergic acid
      diethylamide, atropine and haloperidol. These results that the d-amphetamine
      elicited response was not due mainly to the activation of adrenergic,
      serotoninergic (5-HT), cholinergic or dopaminergic receptors. 3. Increasing
      extracellular calcium or sodium ion concentrations decreased the frequency of the
      spontaneous contraction of the portal vein. However, the ratios of the frequency
      of the spontaneous contraction of the rat portal vein before and after d
      amphetamine treatment in media containing different extracellular calcium or
      sodium concentrations were not significantly altered. Tetrodotoxin did not alter
      the effect of d-amphetamine on the frequency of spontaneous contractions. It
      appeared that calcium and sodium ions may not take part in the effects of d
      amphetamine on the frequency of the portal vein. 4. An increase in extracellular
      potassium ion concentrations increased the frequency of the spontaneous
      contractions of the portal vein. In addition, the ratios of the frequency of the
      spontaneous contractions of the rat portal vein before and after d-amphetamine
      treatment in media containing different extracellular potassium ion
      concentrations were significantly altered. Tetraethylammonium chloride (TEA) and
      4-aminopyridine (4-AP) increased the spontaneous contractions of the portal vein.
      However, TEA and 4-AP did not increase the d-amphetamine-elicited increasing
      effect on the frequency of spontaneous muscle contractions. 5. Levochromakalim, a
      potassium channel opener, decreased the frequency of the spontaneous contractions
      of the portal vein. Levochromakalim also decreased the effect of d-amphetamine on
      the frequency of spontaneous contractions of the muscle. It appeared that
      potassium ion may be associated with the effects of d-amphetamine on the activity
      of the portal vein. 6. d-Amphetamine potentiated, whereas prazosin decreased, the
      noradrenaline-elicited contracture of the rat pulmonary artery in a dose
      dependent manner. 7. d-Amphetamine elicited contracture of the circular muscle of
      rat stomach, whereas it did not alter the frequency of the spontaneous
      contraction of the muscle. 8. Both 5-HT and d-amphetamine elicited the
      contracture of the circular muscle of rat stomach. Ketanserin decreased the 5-HT
      elicited response, whereas it did not alter the d-amphetamine-elicited response
      in the muscle. d-Amphetamine did not alter the frequency of the spontaneous
      contraction of the stomach. 9. It is concluded that d-amphetamine has different
      effects on the frequency of spontaneous smooth muscle contractions. It increased
      the frequency in the portal vein, but it did not alter the frequency in stomach
      circular muscle.

PMID- 9559318
TI  - Imprinting of thymic glucocorticoid receptor and uterine estrogen receptor by a
      synthetic steroid hormone at different times after birth.
AB  - 1. Single allylestrenol treatment (hormonal imprinting) of 3-day old rats reduced
      the density of thymus glucocorticoid receptors and increased the density of
      uterus estrogen receptors at adult age. 2. Similar treatment of 7-, 14-, or 28
      day old animals did not alter the binding capacity of the receptors of the adult
      animals at all. 3. In 3-day-old animals, the direction of imprinting was similar
      to the prenatal imprinting of the thymus glucocorticoid receptor (reduction),
      whereas neonatal treatment of uterine estrogen receptors decreased receptor
      density, and imprinting on the 4th day increased it. This means that the
      imprintability persists only to the 4th day; its consequence can be changed. 4.
      The experiments demonstrate that hormonal imprinting can be provoked by
      allylestrenol not only pre- or neonatally, as was done in previous experiments,
      but also a few days later. The imprintability was lost between the 4th and 8th
      day of life.

PMID- 9559319
TI  - Contractile responses of proximal and distal trachea segments isolated from rats
      subjected to immunological stimulation: role of connective tissue mast cells.
AB  - 1. Anaphylaxis-induced contractions of proximal and distal tracheal segments
      isolated from 14-day ovalbumin (OA)-sensitized rats were studied. 2. OA-induced
      contractions in distal segments were significantly greater than those observed in
      proximal segments. 3. Pretreatment of the rats with compound 48/80 or with sodium
      cromoglycate (SCG) aerosolization significantly reduced OA-induced contractions
      of trachea distal segments, whereas the contractions of proximal segments were
      reduced only by compound 48/80. 4. Mepacrine reduced and indomethacin increased
      the OA-induced contractions in all tracheal segments. Nor-dihydroguaiaretic acid
      increased the OA-induced contractions in distal tracheal segments, whereas
      dazoxiben inhibited the contractions in these same segments; neither of these
      drugs had any effect on the contractions in proximal tracheal segments. 5. The
      depletion of connective tissue mast cells and subsequent in vitro treatment with
      indomethacin increased the OA-induced contractions in both segments. 6. We
      conclude that the contractions of tracheal muscle from OA-sensitized rats depends
      on the topographic and anatomical origin of the airway tissue. 7. Mediators
      released by connective tissue mast cells in proximal and distal segments play a
      pivotal role in this response and may account for variations in the intensity of
      contraction seen after the addition of OA.

PMID- 9559320
TI  - Attempts to classify dependence-liable drugs by using a simple drug
      discrimination test in mice.
AB  - 1. In a simple discrimination test using a two-compartment shuttle box with mice,
      we examined the action properties of dependence-liable drugs. In mice trained to
      discriminate morphine from saline, neither methamphetamine (MAP) nor cocaine
      (COCA) was generalized to the discriminative stimulus effects of morphine. 2.
      Similarly, in mice trained to discriminate MAP from saline, COCA, which is known
      to have neuronal mechanisms in common with MAP, was generalized to the stimulus
      effects of MAP, but morphine was not. 3. Dihydroetorphine (DHE), which has
      receptor mechanisms in common with morphine, was generalized to the
      discriminative stimulus effects of morphine, whereas it was not generalized to
      the effects of MAP. Thus, the present discrimination test might be useful for the
      first screening of compounds with unknown neuronal mechanisms, particularly for
      classification into groups having separate neuropharmacological mechanisms in
      common.

PMID- 9559321
TI  - The effects of captopril and naloxone on restraint-cold-stress- and ethanol
      induced gastric lesions in rats.
AB  - 1. This study was undertaken to investigate the effect of captopril (1
      microgram/kg or 1 mg/kg, i.p.) on the actions of naloxone (5 mg/kg, i.p. in
      gastric ulceration induced by ethanol and restraint-cold-stress. 2. Neither
      naloxone (5 mg/kg, i.p.) nor captopril (1 mg/kg, i.p.) alone induced any change
      in the indices of the ulcer in either group. 3. Captopril at a lower dose (1
      microgram/kg, i.p.), when combined with naloxone (5 mg/kg, i.p.), significantly
      reduced cumulative ulcer length only in the ethanol-treated group (from 54.9 +/-
      7.2 mm to 22.5 +/- 6.2 mm). 4. However, a high dose of captopril (1 mg/kg) plus
      naloxone pretreatment caused a significant reduction in both ethanol (from 54.9
      +/- 7.2 mm to 24.9 +/- 6.5 mm) and restraint-cold-stress (from 19.0 +/- 3.0 mm to
      5.3 +/- 1.0 mm)-induced ulcer formation. 5. Acetylsalycilic acid, when used
      together with captopril, increased the ulcer formation induced by stress. 6.
      Naloxone, by increasing the release of prostaglandins, has been shown to prevent
      ulcer formation induced by several noxious stimuli. 7. Therefore, the effect of
      the combination might be due to the synergistic interaction of both drugs on
      prostaglandin synthesis.

PMID- 9559322
TI  - In vitro studies of the ultrastructural changes induced by guanidine in the
      nerves, muscle fibers and neuromuscular junction of the mouse diaphragm.
AB  - 1. The incubation of mouse isolated diaphragm with guanidine for 60 min produced
      ultrastructural changes in the neuromuscular junction, the intramuscular
      fascicles of the phrenic nerve and the skeletal muscle fibers. 2. The main
      morphological characteristics of both the end terminals and the nerve fibers were
      a swollen appearance and an electron-lucent axoplasm. In addition, the
      mitochondria in these regions were markedly swollen and showed a rarefaction of
      their cristae as well as a "washed aspect" of their matrix. Occasional periaxonal
      vacuoles were present in the myelinated axons. There was a reduction in the
      number of synaptic vesicles, which was accentuated by the enlarged areas of the
      majority of the terminals. 3. Muscle cells underwent a range of morphological
      alterations in the myofibrils and mitochondria. The most drastic type of necrosis
      affecting these cells was complete dissolution of the myofibrils, which resulted
      in an apparently "empty" cell with only the sarcolemma and a few mitochondria
      remaining intact. 4. Tetrodotoxin was unable to provide total protection against
      these guanidine-induced changes. 5. We conclude that the ultrastructural effects
      evoked by guanidine may be associated with modifications in the permeability of
      the axolemmal and sarcolemmal membranes as a result of changes in ionic
      conductance. Such ionic disturbances also interfere with the metabolism of
      mitochondria and the sarcoplasmic reticulum and may account for the well-known
      inhibitory effect of guanidine on K+ channels and consequently on Ca2+ and Na+
      conductances. 6. It is also suggested that the guanidine-induced alterations in
      the presynaptic and postsynaptic sites could have independent mechanisms of
      action.

PMID- 9559323
TI  - Calcium dobesilate increased endothelium-dependent relaxation in isolated rabbit
      aorta.
AB  - 1. The aim of this study was to investigate the effects of calcium dobesilate on
      relaxant and contractile responses in the isolated rabbit aorta. 2. Calcium
      dobesilate (10(-6) and 10(-4) M) shifted the concentration-response curve induced
      by noradrenaline (10(-8)-10(-4) M) downward and to the right, the IC50 being 5.1
      +/- 1.1 x 10(-7) M in the control and 7.5 +/- 1.2 x 10(-6) M and 3.1 +/- 1.9 x
      10(-6) M in the presence of calcium dobesilate, 10(-6) M and 10(-4) M
      respectively. 3. Calcium dobesilate, 10(-5) M, increased the endothelium
      dependent relaxation induced by acetylcholine (10(-8)-10(-5) M) but had no
      actions in the absence of endothelium.

PMID- 9559324
TI  - Effects of chronic ethanol consumption on extramitochondrial fatty acid oxidation
      and ethanol metabolism by rat kidney.
AB  - 1. We evaluated the effects of chronic ethanol consumption on microsomal and
      peroxisomal fatty acid oxidation and on ethanol oxidation by the kidney. 2. When
      mature rats were fed 20% ethanol for 10 weeks, an increase in alcohol
      dehydrogenase and catalase activities were observed in the kidney. 3. Renal
      microsomal and peroxisomal oxidation of fatty acids also increased by the
      treatment, but total cytochrome P450 content did not. 4. We concluded that
      chronic ethanol consumption results in an increased extramitochondrial
      disposition of fatty acids and ethanol oxidation by the kidney.

PMID- 9559326
TI  - Effect of YM435, a novel dopamine DA1 receptor agonist, in a canine model of
      acute congestive heart failure.
AB  - 1. The effects of YM435, a dopamine DA1 receptor agonist, were evaluated in a
      canine model of acute congestive heart failure. 2. The model was induced in open
      chest anesthetized dogs by left anterior descending coronary artery ligation,
      volume loading, and intravenous infusion of angiotensin II. This resulted in a
      moderate and stable congestive heart failure characterized by reduction in
      cardiac output and increases in left ventricular end-diastolic pressure and total
      peripheral vascular resistance. 3. Intravenous infusion of YM435 (1
      microgram/kg/min) significantly decreased left ventricular end-diastolic
      pressure, total peripheral vascular resistance and mean blood pressure and
      significantly increased cardiac output and renal blood flow in this model. 4.
      These results indicate that intravenous infusion of YM435 can improve
      hemodynamics and cardiac function in a canine model of acute congestive heart
      failure. YM435 may be a useful therapeutic agent for the treatment of congestive
      heart failure.

PMID- 9559325
TI  - Effect of hydroxypropyl-beta-cyclodextrin on the central stimulant activity of (
      )-ephedrine and an oxazolidine prodrug in rats.
AB  - 1. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) increases the stability of the
      oxazolidine prodrug toward hydrolysis. 2. The binding constant (Kb) and rate
      constant (Kc) for the hydrolysis of the prodrug-HP-beta-CD complex were
      calculated from the kinetic data. 3. Ion-spray mass spectra confirmed prodrug-HP
      beta-CD complexation. 4. Mass spectral and kinetic data indicated 1:1
      stoichiometry for the complex. 5. A significant elevation of locomotor activity
      in rats was observed when either (-)-ephedrine or the prodrug was administered by
      either the intraperitoneal or the oral route. 6. Addition of HP-beta-CD
      potentiated the central nervous system effect of both (-)-ephedrine and the
      prodrug when administered intraperitoneally. However, when the drugs were
      administered orally, HP-beta-CD caused a decrease in activity.

PMID- 9559327
TI  - Stimulation of duodenal bicarbonate secretion by carbenoxolone in rats: a
      comparative study with prostaglandin E2.
AB  - 1. The effects of carbenoxolone on duodenal HCO3- secretion were examined in
      anesthetized rats and compared with those of prostaglandin E2 (PGE2). 2. After 18
      hr fasting, the duodenal loop (1.7 cm) that was made between the pyloric ring and
      the area just proximal to the outlet of the common bile duct was perfused with
      saline (pH 4.5), the pH of perfusate and the transmucosal potential difference
      (PD) were continuously monitored and HCO3- output was determined by titration
      with 10 mM HCl. 3. Under these conditions, duodenal pH, PD, and HCO3- secretion
      were increased in response to PGE2 (0.3 and 1.0 mg/kg) given intravenously as a
      single injection. Carbenoxolone (0.1-1.0 mg/kg, intravenously) also caused an
      increase in duodenal pH and HCO3- output in a dose-dependent manner, with a
      concomitant rise in PD; at 1 mg/kg, the magnitude of HCO3- output was almost
      equivalent to that induced by PGE2 at 0.3 mg/kg. 4. Prior administration of
      indomethacin, a cyclooxygenase inhibitor (5 mg/kg, subcutaneously), did not
      affect the HCO3- stimulatory action of carbenoxolone or PGE2. 5. Duodenal HCO3-
      secretion was also increased by intravenous injection of dibutylyl adenosine
      3',5'-cyclic monophosphate (dbcAMP) but not by isobutylmethyl xanthine (IBMX; 10
      mg/kg), an inhibitor of phosphodiesterase, but the former action was
      significantly potentiated in the presence of IBMX. Likewise, the pretreatment of
      IBMX significantly enhanced the HCO3- stimulatory action of PGE2 but had no
      effect on the HCO3- response induced by carbenoxolone. 6. These results suggest
      that carbenoxolone stimulates duodenal HCO3- secretion in rats, similar to PGE2
      and this mechanism does not involve endogenous prostaglandins and is not
      associated with the intracellular accumulation of cAMP.

PMID- 9559328
TI  - Effects of ryanodine and cyclopiazonic acid on skinned fibers of ventricular
      myocardium from neonatal and adult rats.
AB  - 1. We examined the effects of ryanodine and cyclopiazonic acid (CPA) on Ca2+
      release from myocardial sarcoplasmic reticulum (SR) with skinned fibers of
      neonatal rat ventricular myocardium. 2. Both ryanodine and CPA concentration
      dependently reduced the caffeine-induced tension in skinned fibers with
      functional SR preserved; 1 microM ryanodine and 20 microM CPA reduced the
      caffeine-induced tension to less than 20% of control values. 3. Both agents had
      no effect on the Ca(2+)-tension relation of skinned fibers without functional SR.
      4. These results suggest that ryanodine and CPA inhibit Ca2+ release from the SR
      and Ca2+ uptake into it in neonatal myocardia. 5. Thus, less-negative inotropic
      effects of ryanodine and CPA on neonatal myocardia compared with those on adult
      myocardia (Agata et al., 1993; Tanaka and Shigenobu, 1989) could not be ascribed
      to lack of drug effects on the SR per se.

PMID- 9559329
TI  - Effects of the antihypertensive drug efonidipine hydrochloride on albuminuria and
      renal histopathology in young spontaneously hypertensive rats with diabetes.
AB  - 1. We investigated the renal protective effect of efonidipine hydrochloride
      (efonidipine, NZ-105) in STZ-induced spontaneously hypertensive rats (SHRs, 8
      weeks of age). Diabetic SHRs were treated with 15 mg/kg/day of efonidipine for 12
      weeks. 2. The dosage of efonidipine was chosen after preliminary studies
      demonstrated that it showed mild antihypertensive action (within 20% decrease of
      systemic blood pressure). 3. In the diabetic SHRs, the excretion of urinary
      albumin was increased (1.78 +/- 0.09 mg/day) at 4 weeks and reached 4.41 +/- 0.12
      mg/day at 12 weeks. The levels of urinary albumin in the diabetic SHRs after
      treatment with efonidipine were significantly less than those in the diabetic
      SHRs at 8 and 12 weeks (P < 0.01). 4. Levels of creatinine clearance were
      decreased in the diabetic SHRs after treatment with efonidipine. 5. In light
      microscopy, the ratio of glomerular tuft to Bowman's areas was significantly
      decreased compared with those in the diabetic SHRs (P < 0.05). 6. These findings
      suggest that efonidipine inhibits the development of albuminuria and glomerular
      enlargement in the streptozotocin-induced diabetic SHRs and may become a useful
      antihypertensive drug with a renal protective effect.

PMID- 9559330
TI  - Effect of chronic administration of L-arginine, NG-nitro-L-arginine or their
      combination on morphine concentration in peripheral tissues and urine of the
      mouse.
AB  - 1. Chronic administration of L-arginine (200 mg/kg, i.p) twice a day for 4 days
      decreased the antinociceptive response to subcutaneously, but not to
      intracerebroventricularly, administered morphine in male Swiss-Webster mice, as
      measured by the tail-flick test. 2. The decreased antinociceptive response to
      morphine was reversed by concurrent administration of NG-nitro-L-arginine (L-NNA)
      (5 mg/kg, IP), an inhibitor of nitric oxide synthase. 3. The concentrations of
      morphine in mice treated chronically with L-arginine and then given morphine (10
      mg/kg, SC) were determined in the peripheral tissues. L-Arginine treatment
      significantly increased the concentration of morphine in spleen and lungs, did
      not modify it in liver, kidneys and urine. L-NNA by itself had no effect on the
      distribution of morphine in peripheral tissues but reversed the changes induced
      by chronic treatment with L-arginine. 4. Acute administration of L-arginine (200
      mg/kg, IP) did not modify either the morphine antinociception or the morphine
      distribution in peripheral tissues. 5. Previous studies from this laboratory
      indicated that chronic treatment with L-arginine decreases the concentration of
      morphine in several brain regions and spinal cord of mice. 6. The facts that
      chronic treatment with L-arginine does not alter antinociception induced by ICV
      administered morphine and it increases the concentration of morphine in
      peripheral tissues while decreasing it in brain regions after peripheral
      administration of morphine suggest that the decreased antinociception induced by
      subcutaneously administered morphine may be related to its decreased entry into
      the brain.

PMID- 9559331
TI  - Effect of the administration of fish oil by gavage on activities of antioxidant
      enzymes of rat lymphoid organs.
AB  - 1. The effect of administration of fish oil by gavage on catalase (CAT),
      glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities of the
      lymphoid organs and liver was compared with those of soybean oil and cocoa
      butter. 2. Fish oil did not affect the activities of SOD and CAT but reduced that
      of GSH-Px in the spleen. In contrast, cocoa butter reduced the CAT activity in
      the thymus and liver, and soybean oil decreased CAT activity in the thymus. 3.
      The content of thiobarbituric acid reactive substances of the lymphoid organs was
      not modified but was increased in plasma.

PMID- 9559332
TI  - The cardiovascular effects of the administration of L-NAME during the early
      posthemorrhagic period.
AB  - 1. The effects of the various doses of NG-nitro-L-arginine methyl ester (L-NAME,
      10 and 30 mg/kg) on some cardiovascular and biochemical parameters during the
      early posthemorrhagic period were studied in anesthetized rabbits subjected to
      hemorrhagic hypovolemia. 2. Hemorrhagic shock was produced by intermittent
      bleeding of 40% of the estimated blood volume for 15 min. Blood samples were
      taken before and after bleeding (0, 15 and 60 min). Simultaneously, the mean
      arterial pressure (MAP) and the heart rate (HR) were measured. Hemorrhaged
      rabbits were treated by L-NAME10 or L-NAME30 (10 or 30 mg/kg, i.v. bolus
      injection, respectively) or the corresponding volumes of saline (0.6 ml, i.v.
      bolus) immediately after the end of bleeding. 3. The observed cardiovascular
      parameters (MAP, HR) were significantly reduced after the end of bleeding in all
      rabbits. 4. The rise of the MAP was significantly more pronounced 30 min after
      the injection of L-NAME30 in comparison with the corresponding values in the
      saline (S) group. In contrast, L-NAME10 produced only a small, insignificant
      increase in the MAP in hemorrhaged rabbits. 5. The L-NAME30-induced rise of the
      MAP was accompanied by a severe bradycardia, hyperkalemia and an aggravated
      metabolic acidosis, more severe than the corresponding disturbance of the acid
      base status in the S group. The changes in the acid-base parameters were observed
      both in arterial (pH, excess base) and in venous blood (pH) of hemorrhaged
      rabbits. 6. In conclusion, the i.v. bolus injection of L-NAME30 (immediately
      after the end of bleeding) produced a significant increase in the MAP during the
      first hour after the injury, but the presumable inhibition of the endothelial
      constitutive nitric oxide synthase during the early posthemorrhagic period
      resulted in severe cardiovascular and metabolic disturbances.

PMID- 9559333
TI  - Protective effects of grape seed proanthocyanidins and selected antioxidants
      against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation,
      and peritoneal macrophage activation in mice.
AB  - 1. The comparative protective abilities of a grape seed proanthocyanidin extract
      (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100
      mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced lipid peroxidation and DNA fragmentation in the hepatic and brain
      tissues, as well as production of reactive oxygen species by peritoneal
      macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin
      C, VES and beta-carotene decreased TPA-induced production of reactive oxygen
      species, as evidenced by decreases in the chemiluminescence response in
      peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and
      cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively,
      compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA
      induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively,
      in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain
      tissues, at the doses that were used. Similar results were observed with respect
      to lipid peroxidation in hepatic mitochondria and microsomes and in brain
      homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA-induced lipid
      peroxidation and DNA fragmentation in liver and brain, as well as a dose
      dependent inhibition of TPA-induced reactive oxygen species production in
      peritoneal macrophages. 5. GSPE and other antioxidants provided significant
      protection against TPA-induced oxidative damage, with GSPE providing better
      protection than did other antioxidants at the doses that were employed.

PMID- 9559334
TI  - Cyclosporin A and FK-506 inhibit development of superantigen-potentiated collagen
      induced arthritis in mice.
AB  - 1. Staphylococcal enterotoxine B (SEB; superantigen) accelerated the onset of
      arthritis in mice preimmunized with type II collagen (SEB-potentiated collagen
      induced arthritis). Cyclosporin A and FK-506 inhibited the induction and
      development of clinical signs and histopathological changes of SEB-potentiated
      collagen-induced arthritis in mice. 2. Simultaneously, both cyclosporin A and FK
      506 inhibited the development of humoral and cellular immunity to type II
      collagen. 3. The expression of IL-2 receptor (CD25) by SEB on splenocyte T cells
      from collagen-preimmunized mice was inhibited by both agents in ex vivo
      experimentation.

PMID- 9559335
TI  - Inhibition by ginsenosides Rb1 and Rg1 of methamphetamine-induced hyperactivity,
      conditioned place preference and postsynaptic dopamine receptor supersensitivity
      in mice.
AB  - The ginsenosides Rb1 and Rg1, the major components of ginseng saponin, inhibited
      not only methamphetamine-induced hyperactivity but also conditioned place
      preference (CPP) in mice following a single or repeated administration. Dopamine
      (DA) receptor supersensitivity, which developed in methamphetamine-induced CPP
      mice, was also inhibited by both Rb1 and Rg1. Therefore, the present results
      suggest that Rb1 and Rg1 may be the active components of ginseng saponin in the
      modulation of methamphetamine-induced dopaminergic behaviors such as
      hyperactivity and CPP, supporting our previous conclusion that ginseng saponin
      might modulate methamphetamine-induced dysfunction at both the pre- and
      postsynaptic DA receptors.

PMID- 9559336
TI  - Miconazole as inflammatory agent. II: Time course of pleurisy and drug
      interference.
AB  - 1. Miconazole-induced pleurisy was characterized by edema development and
      leukocyte infiltration. 2. This response was inhibited by chlorpheniramine,
      methysergide and steroidal and nonsteroidal anti-inflammatory drugs. 3. After
      miconazole injection, no mast cells were found in the pleural cavity. 4. Our
      results support the concept that biogenic amines released from mast cells and
      cyclooxygenase-derived mediators may contribute to the pathogenesis and evolution
      of miconazole inflammation.

PMID- 9559337
TI  - Adhesins of immunoglobulin-like superfamily from earthworm Eisenia foetida.
AB  - 1. From the biologically active extract (G-90) isolated from the tissue
      homogenate of Eisenia foetida immunoglobulin-like structures were isolated and
      named G-90/4. 2. G-90/4 in nanogram concentrations stimulated cell proliferation
      more than did the original G-90. It lyses cells in microgram concentrations. 3. G
      90/4 acts as an adhesion molecule between the receptors of adjacent cells. 4. The
      increase in proliferative activity was accompanied by the elevation of
      cytoplasmic protein containing tyrosine. 5. Immunohistochemical analyses confirm
      immunoglobulin-like transmembrane structures in the connective and muscular
      tissues of E. foetida.

PMID- 9559338
TI  - 6-OHDA lesions to amygdala and hippocampus attenuate memory-enhancing effect of
      the 3-7 fragment of angiotensin II.
AB  - We have previously shown that facilitatory effect of angiotensin II (AII) on the
      retrieval of memory is mediated by the dopaminergic system. In the present study,
      we searched for the influence of the 3-7 fragment of angiotensin II [AII(3-7)] on
      the retrieval processes in a passive avoidance situation after bilateral 6-OHDA
      lesions to the central amygdala (CA) and the CA4 field of the hippocampus (HI).
      AII(3-7) given 15 min before the retention testing, at the
      intracerebroventricular dose of 1 nmol, significantly prolonged avoidance
      latencies in sham-operated rats (i.e. improved retrieval of memory for the
      electric footshock experienced during the learning trial). Bilateral lesions to
      CA totally abolished, and to HI significantly diminished, this facilitatory
      effect. An increase of spontaneous locomotor activity in rats lesioned to CA and
      a decrease in rats lesioned to HI were unlikely to interfere with the cognitive
      effect of AII (3-7). These results suggest that the anatomical substrate of
      facilitating retrieval of information activity of AII(3-7) is closely related to
      the dopaminergic projection from the ventral tegmental area and substantia nigra
      to CA and HI.

PMID- 9559339
TI  - An FHIT tumor suppressor gene?
AB  - The FRA3B at 3p14.2 is the most common of the constitutive aphidicolin-inducible
      fragile sites. Using independent approaches, four groups of investigators have
      cloned and characterized this fragile site. The results of these studies have
      revealed that the FRA3B differs from other heretofore cloned rare fragile sites.
      First, instability as manifested by chromosome breakage occurs over a large
      region of DNA, encompassing at least 500 kb. Second, sequence analysis has not
      revealed trinucleotide repeat motifs, characteristic of the rare fragile sites.
      In addition to containing the FRA3B, band 3p14 is also likely to contain a tumor
      suppressor gene, as evidenced by the presence of deletions, rearrangements, and
      allele loss in a variety of human tumors, including lung, renal, nasopharyngeal,
      cervical, and breast carcinomas. The recently cloned FHIT gene in 3p14.2 is a
      promising candidate tumor suppressor gene, since aberrant FHIT transcripts have
      been found in a significant proportion of cancer-derived cell lines and primary
      tumors of the digestive and respiratory tracts. Nonetheless, several lines of
      evidence garnered over the past year have called into question the role of FHIT
      as a classical tumor suppressor gene, and raised the question of whether its
      apparent involvement simply reflects its location within an unstable region of
      the genome. In the following study, we have summarized the evidence in support of
      FHIT as a tumor suppressor gene as well as evidence against such a role, and the
      experimental evidence needed to demonstrate that FHIT functions as a tumor
      suppressor gene in the pathogenesis of human tumors. The paradigm of FHIT
      emphasizes that confirming the role of a candidate tumor suppressor gene may
      prove difficult, particularly for those genes that are located in genetically
      unstable regions.

PMID- 9559340
TI  - Detection of APC mutations by a yeast-based protein truncation test (YPTT).
AB  - APC gene mutations play a role in the initiation step of colorectal
      carcinogenesis in both familial adenomatous polyposis (FAP) and non-FAP patients.
      Almost all of the APC mutations are nonsense or frameshift mutations, which
      truncate the APC protein and are thought to inactivate normal APC function. We
      show a novel method for detecting nonsense and frameshift APC gene mutations by
      using Saccharomyces cerevisiae. Polymerase chain reaction (PCR)-amplified APC
      fragments are cloned directly into yeast expression vectors in vivo, and the
      yeast expresses a hemagglutinin epitope (HA)-tagged APC peptide. When an APC
      fragment contains a nonsense or frameshift mutation, HA-tagged truncating APC
      peptide can be detected by Western blotting using an anti-HA antibody. We
      identified both germ-line and somatic APC mutations in patients with FAP and non
      FAP colorectal tumors, respectively. This method, called the yeast-based protein
      truncation test (YPTT), is simple and fairly cheap, and it can be applied to any
      genes that are inactivated by protein truncating mutations.

PMID- 9559341
TI  - Gain of 3q and deletion of 11q22 are frequent aberrations in mantle cell
      lymphoma.
AB  - We used comparative genomic hybridization (CGH) to screen for DNA copy number
      changes in 34 specimens from 27 cases of mantle cell lymphoma (MCL). The most
      common gains were detected at 3q (52%), 8q (30%), and 15q (26%), whereas the most
      frequent losses involved 13q (41%), 1p (33%), 6q (30%), 9p (30%), and 11q (30%).
      The gain of 3q, with a minimal common region at 3q26.1-27, appeared in more than
      half of the lymphomas, suggesting the location of an important oncogene here. A
      common deleted region at 11q22 was found in one-third of the patients, which
      suggests that this region may harbor a tumor suppressor gene important in the
      tumorigenesis of MCL. The mean number of changes was higher in more aggressive
      blastoid variants of MCL than in lymphomas with typical morphology. Our results
      show that the chromosomal regions affected in MCL are highly consistent and are
      different from those seen in other types of non-Hodgkin's lymphoma.

PMID- 9559342
TI  - Allelotyping demonstrates common and distinct patterns of chromosomal loss in
      human lung cancer types.
AB  - Allelic loss is a hallmark of tumor suppressor gene (TSG) inactivation. We have
      allelotyped 29 paired lymphoblastoid and lung cancer cell lines derived from 11
      patients with small cell (SCLC) and 18 patients with non-small cell lung
      carcinomas (NSCLC). Statistical analysis indicated that a threshold of 30%
      separated non-random allelic loss from the random genetic deletions of
      malignancy. We have identified non-random allelic loss at 42 of 54 (78%) specific
      chromosomal regions examined, with 22 regions (52%) common between the two major
      lung cancer histologic types. There were 3 regions (7%) with allelic loss
      specific for SCLC and 17 regions (41%) specific for NSCLC. Furthermore, there
      were significant differences in loss of heterozygosity (LOH) frequencies between
      NSCLC and SCLC at 13 regions on eight chromosome arms (3p, 5q, 6q, 9p, 10q, 11p,
      13q, and 19p). Eight homozygous deletions were present in seven cell lines at
      four regions, 3p12, 3p14.2, 9p21, and 10q23-25. We have also identified novel
      sites of chromosomal deletions. In particular, there was frequent loss at 11p13
      in SCLC and loss at 6p21.3 and 13q12.3 in NSCLC. In this study, we demonstrate
      that a) non-random allelic losses in lung cancer involve multiple regions; b)
      some losses are common to both NSCLC and SCLC subtypes, whereas others are
      subtype specific; c) there are genetic deletions at novel chromosomal regions;
      and d) several homozygous deletions have been noted. Our studies demonstrate the
      usefulness of continuous cell lines for detailed allelotyping, for comparing
      genetic abnormalities between SCLC and NSCLC, and for identifying homozygous
      deletions.

PMID- 9559343
TI  - Mutational inactivation of aminoacylase-I in a small cell lung cancer cell line.
AB  - Small cell lung cancer (SCLC) cell lines and tumors invariably exhibit loss of
      heterozygosity (LOH) or, in rare cases, homozygous deletions involving part or
      all of chromosome arm 3p, suggesting the presence of 1 or more tumor-suppressor
      genes in this region. The gene encoding aminoacylase-I (ACYl) is localized on
      chromosome segment 3p21.1. ACYl enzymatic activity, protein, and mRNA have been
      demonstrated to be expressed at either undetectable or very low levels in a group
      of SCLC cell lines and tumors. The demonstration of mutational inactivation of
      ACYl would support the hypothesis that ACYl inactivation in SCLC confers a
      selective growth advantage. One of four SCLC cell lines with undetectable Acyl
      enzymatic activity and protein exhibited a compound mutation: nonconservative
      missense point mutations at codons 195 and 254. No wildtype sequence transcripts
      were identified in the cell line. Although nonmutational mechanisms for low or
      undetectable ACYl enzymatic activity, protein, and mRNA expression are most
      frequently operant in SCLC, the demonstration of a mutation supports selection
      for ACYl inactivation. Analysis of normal liver and a liver metastasis from the
      same patient from whom the NCI-H711 cell line was derived demonstrated that the
      mutation was neither germline nor an early event in the development of SCLC. It
      is of interest that several genes involved in the regulation of intracellular
      protein degradation are encoded by chromosome band 3p21 and display unusual
      expression in SCLC. The presence of other loci involved in protein degradation on
      chromosome band 3p21 and their aberrant expression in SCLC suggest that a variety
      of mechanisms involved in the normal degradation of intracellular proteins may be
      perturbed in this neoplasm.

PMID- 9559344
TI  - Investigation of the genes for RET and its ligand complex, GDNF/GFR alpha-I, in
      small cell lung carcinoma.
AB  - RET is a receptor tyrosine kinase expressed in neuroendocrine cells and in tumors
      of these cell types. RET activation may be mediated by a ligand complex
      comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF family
      receptor alpha-1 (GFR alpha-1). Activating RET mutations are found in the
      inherited cancer syndrome multiple endocrine neoplasia type 2 and in a subset of
      the related sporadic tumors, medullary thyroid carcinoma and pheochromocytoma,
      both being derived from neuroendocrine tissues. In one small study, mutations
      were identified in another tumor with neuroendocrine features, small cell lung
      carcinoma (SCLC). To determine whether RET mutations contribute to the
      pathogenesis of SCLC, we examined a panel of 54 SCLC cell lines. No mutations
      were identified in RET exons 10, 11, and 13-16, regions previously implicated in
      SCLC or other neuroendocrine tumors. We further examined the expression pattern
      of RET and the genes encoding the components of its ligand complex GDNF and GFR
      alpha-1, in 21 SCLC lines by using RT-PCR. Although we found no consistent
      pattern of expression for these three genes, RET was expressed in 57% of SCLC
      lines. Thus, although RET mutations appear unlikely to be an important step in
      the tumorigenesis of SCLC, the frequent expression of this gene suggests that RET
      may have a mitogenic role in a subset of SCLC cell lines.

PMID- 9559345
TI  - Loss of 18q predicts poor survival of patients with squamous cell carcinoma of
      the head and neck.
AB  - Tumor suppressor genes play an important role in normal growth regulation. Loss
      or inactivation of these genes has been implicated in the development of squamous
      cell cancer and progression of neoplasia. Previous studies in our laboratories
      have implicated chromosome 18 long-arm deletions as a possible marker of
      progression in head and neck squamous cell cancer (HNSCC). To test this
      hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity
      (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA
      were extracted from fresh tissue and paraffin blocks and were amplified by PCR
      using primers for three microsatellite repeat polymorphisms in 18q (D18S336,
      D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients
      had a statistically significantly poorer two-year survival compared to those
      without 18q LOH (30% vs. 63%; P = 0.008). In a Cox proportional hazards model in
      which time from diagnosis to death was the outcome variable, patients with 18q
      LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q
      LOH was placed in a multivariate model controlling for possible confounders in
      the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The
      observation of a prognostic association between 18q LOH and poor patient survival
      suggests that loss of an 18q tumor suppressor gene or genes is important in the
      progression of HNSCC.

PMID- 9559346
TI  - Investigation of genetic alterations associated with the grade of astrocytic
      tumor by comparative genomic hybridization.
AB  - Comparative genomic hybridization (CGH) is a technique that allows the detection
      of losses and gains in DNA copy number across the entire genome. We used CGH to
      study the genetic alterations that occur in primary astrocytomas, including 14
      glioblastomas (GBM), 12 anaplastic astrocytomas (AA), and 7 low-grade
      astrocytomas (LGA). The average numbers of total aberrations in GBM, AA, and LGA
      were 9.7, 5.4, and 4.0, respectively. The average number of DNA sequence losses
      in GBM was significantly higher than that in AA or LGA (P < 0.01). Frequently
      altered regions (> eight cases) observed in all grades of astrocytoma were 7p13
      p12 (gain), 7q31 (gain), 8q24.1-q24.2 (gain), 9p21 (loss), 10p12-p11 (loss),
      10q22-qter (loss), 13q21-q22 (loss), and 20q13.1-q13.2 (gain). Loss of 9p, 10p,
      or 10q, and the gain or amplification of 7p, were observed frequently in GBM
      (64%, 57%, 64%, and 50% of cases, respectively). Frequent alterations found in AA
      were losses of 9p, 10q, and 13q, and gains of 1q, chromosome 7, 11q, and Xq.
      Whereas 7p13-p11 amplification occurred exclusively in cases with the loss of all
      or part of chromosome 10, this change never occurred in cases having an increase
      in copy number of 8q, which was the most frequent change observed in LGA (four of
      seven cases). These results may indicate that an increase in copy number of 8q is
      an important event in GBM, with a genetic pathway, which is distinct from that in
      GBM with 7p amplification.

PMID- 9559347
TI  - Novel WT1 mutation, 11p LOH, and t(7;12) (p22;q22) chromosomal translocation
      identified in a Wilms' tumor case.
AB  - About 5-10% of sporadic Wilms' tumors (WT) are associated with mutations in the
      Wilms' tumor 1 gene (WT1). More than 90% of patients with Denys-Drash syndrome
      (DDS; characterized by renal nephropathy, gonadal anomaly, and predisposition to
      WT) show constitutional intragenic WT1 mutations. We describe a novel WT1 stop
      mutation in exon 2. This heterozygous germline mutation was detected in a one
      year-old girl who was bilaterally affected with Wilms' tumor but without any
      other clinical manifestations of DDS. The C-to-A transversion is predicted to
      result in a polypeptide comprising only the first 165 amino acids of the WT1
      protein. Loss of heterozygosity (LOH) studies comparing tumor DNA with lymphocyte
      DNA revealed LOH for the entire short arm of chromosome 11 in tumor tissue. In
      addition to the chromosome 11 lesions, the tumor showed a seemingly balanced
      chromosomal translocation t(7;12) (p22;q22) as the only visible cytogenetic
      aberration.

PMID- 9559348
TI  - Discontinuing antidepressant treatment in major depression.
AB  - Maintenance treatments in bipolar disorders and schizophrenia are securely
      established, and their discontinuation is associated with high but modifiable
      risk of early relapse. The benefits of long-term antidepressant treatment in
      major depression and the risks of discontinuing medication at various times after
      clinical recovery from acute depression are not as well defined. Computerized
      searching found 27 studies with data on depression risk over time including a
      total of 3037 depressive patients treated for 5.78 (0-48) months and then
      followed for 16.6 (5-66) months with antidepressants continued or discontinued.
      Compared with patients whose antidepressants were discontinued, those with
      continued treatment showed much lower relapse rates (1.85 vs. 6.24%/month),
      longer time to 50% relapse (48.0 vs. 14.2 months), and lower 12-month relapse
      risk (19.5 vs. 44.8%) (all p < 0.001). However, longer prior treatment did not
      yield lower postdiscontinuation relapse risk, and differences in relapses off
      versus on antidepressants fell markedly with longer follow-up. Contrary to
      prediction, gradual discontinuation (dose-tapering or use of long-acting agents)
      did not yield lower relapse rates. Relapse risk was not associated with
      diagnostic criteria. More previous illness (particularly three or more prior
      episodes or a chronic course) was strongly associated with higher relapse risk
      after discontinuation of antidepressants but had no effect on response to
      continued treatment; patients with infrequent prior illness showed only minor
      relapse differences between drug and placebo treatment.

PMID- 9559349
TI  - A glutamatergic model of ECT-induced memory dysfunction.
AB  - Electroconvulsive therapy (ECT) is an efficacious treatment for a variety of
      neuropsychiatric conditions including major depression, mania, catatonia,
      Parkinson's disease, and neuroleptic malignant syndrome. However, ECT-induced
      memory dysfunction complicates the treatment and is a major concern for both
      patients and providers. We briefly review ECT-induced memory dysfunction and
      propose a glutamatergic model for it. (Articles examined were retrieved by a
      Medline search on the terms electroconvulsion and glutamate, with language
      limited to English.) Specifically, we hypothesize that ECT-induced memory
      dysfunction results from neuronal insults due to excessive release of excitatory
      amino acids and activation of their receptors, which produce cation and water
      flux and reversible oxidative stress. This model offers multiple testable
      hypotheses; exploring them may help to identify the risk factors for this
      significant side effect of ECT treatment and may thus yield effective agents for
      its prevention and treatment.

PMID- 9559350
TI  - Enactment and the treatment of abuse survivors.
AB  - Regardless of the approach employed, treatment of patients with histories of
      sexual or other abuse is a formidable challenge. One reason for this is the
      vulnerability to "enactment" inherent in therapeutic work with such patients.
      Enactment is a recently elaborated psychoanalytic notion, defined as a pattern of
      nonverbal interactional behavior between the two parties in a therapeutic
      situation, with unconscious meaning for both. It involves mutual projective
      identification between therapist and patient. This paper clarifies the nature of
      enactment (conceptualized here as involving either refusal or actualization of
      the transference by the therapist) and its treatment implications. Transference
      countertransference enactment paradigms encountered in work with survivors of
      abuse are presented. The therapeutic consequences of failing to recognize and
      respond to such enactments in work with these patients are explored. Unrecognized
      enactments may lead therapists unwittingly to abdicate the therapeutic role by
      becoming abusive, abused or vicariously traumatized, excessively guilty,
      seductive, overinvolved, and/or exhortatory or to implant false memories. Ways of
      utilizing enactment to advance treatment are also described and illustrated.

PMID- 9559352
TI  - St. John's wort.

PMID- 9559351
TI  - When the patient asks the doctor's help in ending life: a request for assisted
      suicide by a man with AIDS.

PMID- 9559353
TI  - Impulsive aggression: a behavior in search of clinical definition.

PMID- 9559354
TI  - Gender and health policy.

PMID- 9559355
TI  - Trends in the evaluation of managed mental health care.

PMID- 9559356
TI  - Effect of gamma irradiation on unsporulated and sporulated Toxoplasma gondii
      oocysts.
AB  - The effect of 137Cs irradiation on unsporulated and sporulated Toxoplasma gondii
      oocysts was investigated as a model system for sterilisation of fruit
      contaminated with other coccidia such as Cyclospora or Cryptosporidium.
      Unsporulated oocysts irradiated at > or = 0.4 to 0.8 kGy sporulated but were not
      infective to mice. Sporulated oocysts irradiated at > or = 0.4 kGy were able to
      excyst, and sporozoites were infective but not capable of inducing a viable
      infection in mice. Toxoplasma gondii was detected in histologic sections of mice
      up to 5 days but not at 7 days after feeding oocysts irradiated at 0.5 kGy.
      Transmission electron microscopy revealed that sporozoites from irradiated
      oocysts penetrated enterocytes and all cells in the lamina propria except for red
      blood cells. Sporozoites appeared normal ultrastructurally and formed a typical
      parasitophorous vacuole containing a well-developed tubulovesicular membrane
      network. Raspberries inoculated with sporulated T. gondii oocysts were rendered
      innocuous after irradiation at 0.4 kGy. Results indicate that irradiation at 0.5
      kGy is effective in "killing" coccidian oocysts on fruits and vegetables.

PMID- 9559357
TI  - Multiparasite communities in animals and humans: frequency, structure and
      pathogenic significance.
AB  - Individual humans and animals are subject to infection by a variety of parasites
      (broadly defined to include viruses, bacteria and other non-protozoan
      microparasites) at any one time. Multiple parasite infections occur frequently in
      populations of wild animals as well as in humans from developing countries. In
      some species and regions, hosts with multiple infections are more common than
      hosts with either no infection or a single infection. Studies, predominantly on
      animals, show that a wide variety of environmental and host-dependent factors can
      influence the structure and dynamics of the communities of parasites that make up
      these multiple infections. In addition, synergistic and competitive interactions
      can occur between parasite species, which can influence the likelihood of their
      successful transmission to other hosts and increase or decrease their overall
      pathogenic impact. This review summarises aspects of our current knowledge on the
      frequency of multiparasite infections, the factors which influence them, and
      their pathogenic significance.

PMID- 9559358
TI  - Caenorhabditis elegans as a model for parasitic nematodes.
AB  - Caenorhabditis elegans has become a popular model system for genetic and
      molecular research, since it is easy to maintain and has a very fast life-cycle.
      Its genome is small and a virtually complete physical map in the form of cosmids
      and YAC clones exists. Thus it was chosen as a model system by the Genome Project
      for sequencing, and it is expected that by 1998 the complete sequence (100
      million bp) will be available. The accumulated wealth of information about C.
      elegans should be a boon for nematode parasitologists, as many aspects of gene
      regulation and function can be studied in this simple model system. A large array
      of techniques is available to study many aspects of C. elegans biology. In
      combination with genome projects for parasitic nematodes, conserved genes can be
      identified rapidly. We expect many new areas of fertile research that will lead
      to new insights in helminth parasitology, which are based not only on the
      information gained from C. elegans per se, but also from its use as a
      heterologous system to study parasitic genes.

PMID- 9559359
TI  - Levamisole binding sites in Haemonchus contortus.
AB  - Larval and adult extracts from isolates of Haemonchus contortus were assayed for
      specific [3H]levamisole binding activity. All of the tissue preparations
      displayed [3H]levamisole binding sites. The sensitive isolate SE and resistant
      isolate RJ showed no differences in larval and adult binding data. Larval SE
      extracts had higher receptor density (Bmax = 648 fmol mg-1) and dissociation
      constant (Kd = 1.28 microM) for [3H]levamisole than larval extracts of the
      American isolate RUSA (Bmax = 87 fmol mg-1 and Kd = 0.15 microM). Extracts of
      adult SE and RUSA isolates contain as much as 327 fmol mg-1 of protein and 205
      fmol mg-1 of protein, respectively, and similar dissociation constants (Kd = 0.77
      microM and Kd = 0.81 microM, respectively). There was a good correlation between
      specific binding activity of larval and adult extracts in both SE and RUSA
      isolates. The nicotinic cholinergic antagonist alpha-bungarotoxin had no effects
      in either isolate on [3H]levamisole binding activity. The results confirm that
      levamisole acts at a cholinergic receptor in H. contortus, and suggest that
      target site modification could be involved in the development of levamisole
      resistance.

PMID- 9559360
TI  - Pruritus and dermal response to insect antigens in sheep infested with Bovicola
      ovis.
AB  - This study examined the relationships among louse density, pruritus and dermal
      response to insect antigens in sheep infested with Bovicola ovis. Polypay and
      Columbia ewes were allocated to two groups, infested and naive, and louse
      densities and pruritus were monitored for 15 months. Ten months after the initial
      infestation, all sheep were tested for hypersensitivity on the midside and ears
      by intradermal injection of soluble extracts of B. ovis, Stomoxys calcitrans and
      Musca autumnalis. The areas of skin reactions were measured at 20 min, 1, 3 and
      24 h after injection and skin thickness was measured at 24 h. Louse densities on
      Polypays were approximately 10 times greater than on Columbias, and pruritus was
      correlated with louse numbers at most inspections. Most pruritic behaviour was
      directed to the sides of infested sheep. Wheal and flare reactions developed
      rapidly to all extracts in both infested and naive ewes. Reactions to louse
      extract were larger in infested than naive sheep at all four times after
      injection. In the infested Polypays, reactions to louse extract were greater than
      to the fly extracts, but in naive sheep there was little difference among
      extracts. Reactions in naive Columbias were larger than in naive Polypays at 20
      min, 1 and 3 h, but had almost completely abated in both groups at 24 h.
      Reactions in infested Columbias were greater than in infested Polypays at 20 min,
      but at 24 h reactions in the Polypays were larger. Louse numbers and pruritus
      were correlated with wheal areas and skin thickness at 24 h, but there was little
      relationship with the size of reactions at earlier times. These findings are
      consistent with the development of a hypersensitive response to B. ovis and
      suggest that dermal reactions to lice may influence sheep susceptibility.

PMID- 9559361
TI  - Identification and characterisation of a dense granule-associated protein in
      Neospora caninum tachyzoites.
AB  - Neospora caninum is an apicomplexan parasite which is morphologically and
      ultrastructurally very similar to Toxoplasma gondii. In order to identify
      molecules involved in host cell entry and subsequent modification of the
      parasitophorous vacuole, a polyclonal antiserum directed against N. caninum
      tachyzoites was raised in a rabbit. Subcellular fractionation of tachyzoites was
      performed using the non-ionic detergent Triton-X-114. Membrane fractions were
      analysed by immunoblotting using the polyclonal antiserum. One of the
      immunoreactive protein bands had a mol. wt of 33,000 and was subsequently named
      Nc-p33. Affinity-purified anti-Nc-p33 antibodies were used to characterise this
      polypeptide using SDS-PAGE, isoelectric focusing, Western blot analysis and
      immuno-EM. Nc-p33 was found in two isolates of N. caninum (NC-1 and Liverpool),
      but could not be detected in T. gondii tachyzoites. Immunogold EM revealed that
      Nc-p33 constituted a dense granule-associated protein, and Western blotting
      demonstrated that Nc-p33 was most likely identical to the recently described
      antigen NCDG1. Shortly after invasion, this dense granule protein was targeted to
      the parasitophorous vacuole membrane, and, at later timepoints after infection,
      was also found on the parasitophorous vacuolar network. This suggested that Nc
      p33 could play a functional role in the modification of the parasitophorous
      vacuole and its membrane.

PMID- 9559362
TI  - Inhibition of growth of Lucilia cuprina larvae using serum from sheep vaccinated
      with first-instar larval antigens.
AB  - Whole first-instar Lucilia cuprina larvae were homogenised and sequentially
      extracted with a series of buffers of progressively more severe solubilising
      power. The final extract, using a buffer containing 6 M-urea, was fractionated by
      preparative isoelectric focussing. At each step in this process, protein
      fractions were tested in sheep vaccination trials for their ability to induce
      immune responses affecting the growth of L. cuprina larvae which fed on the sera
      from vaccinated sheep. One isoelectric focussing fraction (pH 5.9-6.7) containing
      a number of larval proteins induced an immune response which inhibited the growth
      of larvae by a mean of 84 +/- 7% in an in vitro feeding bioassay. The recovery of
      larvae after feeding on sera from sheep vaccinated with this fraction was
      significantly reduced by 35 +/- 13%. This antilarval effect was shown to be
      mediated by ingested ovine antibodies. Immunofluorescence and immunogold
      localisations showed that the immune response was directed at proteins from the
      larval peritrophic membrane, larval cuticle and, to lesser extent, basement
      membranes and microvilli of digestive epithelial cells. Electron microscopic
      examination of larvae feeding on sera from sheep vaccinated with this fraction
      showed that the normally semi-permeable peritrophic membrane was blocked on the
      luminal side by an electron-lucent layer of undefined composition. It is
      postulated that this layer prevents nutrients from moving from the gut to the
      underlying digestive epithelial cells, thereby starving the larvae. The sera from
      sheep vaccinated with another isoelectric focussing fraction (pH 3.4-5.5) reduced
      the mean larval weight by 56 +/- 13% without significant effects on larval
      survival.

PMID- 9559363
TI  - The effects of excretions/secretions of Ostertagia circumcincta on ovine abomasal
      tissues in vitro.
AB  - Products excreted/secreted by Ostertagia circumcincta stimulated the in vitro
      release of pepsinogen from intact abomasal mucosal sheets and caused the
      contraction of strips of abomasal smooth muscle, also in vitro. However,
      responses occurred only when tissues had been derived from animals that were
      assumed to have experienced prior exposure to the parasite. The overall median
      responses for pepsinogen secretion in response to ES, expressed as the ratio of
      stimulated secretion to basal secretion, were 1.8 for previously exposed animals
      and 0.9 for parasite-naive animals. For the smooth muscle from the previously
      exposed animals, the overall median response to ES, expressed as a percentage of
      the maximal response to carbachol in the same tissues, was 27.0. No responses
      were seen in muscle from any parasite-naive animal. These results suggest that
      the responses obtained were hypersensitivity reactions to antigens released by
      the worms during in vitro culture, and occurring in tissues from animals
      sensitised by exposure to O. circumcincta in the natural environment.

PMID- 9559364
TI  - Latitudinal differences in species and community richness and in community
      structure of metazoan endo- and ectoparasites of marine teleost fish.
AB  - Relative species diversity of gastrointestinal helminths of 55 teleost fish
      species did not differ significantly at different latitudes, whereas relative
      species diversity of metazoan ectoparasites on the heads and gills of 108 teleost
      fish species showed a significant increase with decreasing latitude and from deep
      to surface waters. Abundance of endoparasites also was the same at all latitudes,
      whereas abundance of ectoparasites increased with decreasing latitude and from
      deep to shallow waters. A comparative analysis using phylogenetically independent
      contrasts supported these conclusions. Possible reasons for the differences
      between endo- and ectoparasites are discussed. A detailed analysis of the
      community structure of gastrointestinal helminths of five Antarctic and three
      tropical teleosts and of metazoan ectoparasites on the heads and gills of five
      Antarctic and seven tropical fish species showed the following: abundance and
      prevalence of infection of endoparasites are similar in Antarctic and tropical
      fish, but are much greater for tropical than for Antarctic ectoparasites.
      Relative species diversity of endoparasites is similar for Antarctic and tropical
      endoparasites, but much greater for tropical than Antarctic ectoparasites. In
      both Antarctic and tropical fish, different fish of the same species may have
      different dominant species of endo- and ectoparasites, although there is a
      greater range of dominant species of tropical ectoparasites, a consequence of the
      greater species pool available. The most dominant parasite (irrespective of
      species) represented 80-99% of all endoparasites of Antarctic, and about 50-80%
      of all endoparasites of tropical fish. The most dominant parasites (irrespective
      of species) represented about 90-100% of all ectoparasites of Antarctic, and
      about 20-70% of all ectoparasites of tropical fish, the difference a consequence
      of the greater species pool of tropical ectoparasites available. The data suggest
      that both endo- and ectoparasites live in assemblages not structured by
      interspecific competition.

PMID- 9559365
TI  - The development and persistence of phanerozoites in experimental infections of
      Plasmodium sasai.
AB  - Phanerozoites of Plasmodium sasai parasitised virtually all tissues of Takydromus
      tachydromoides infected by inoculation of blood, and persisted until each lizard
      died, 2-296 days postinoculation. At 4 days postinoculation, phanerozoites were
      larger than at 2 and 6 days; many were observed rupturing, suggesing a maturation
      time of approximately 4 days. The proliferation of phanerozoites decreased after
      2 months postinoculation, but small phanerozoites were still present at 296 days.
      A few encysted phanerozoites (chronozoites) appeared at 2 days postinoculation,
      but from 75 days comprised over half of parasites present in most tissues. Some
      differences in mean size and shape were evident among various organs.
      Phanerozoites occurred in connective tissue and endothelium in all organs, but
      were most plentiful in the heart in every infection, often occurring in clusters
      of > 30 schizonts, with up to 105 found in single sections at 4 days.
      Phanerozoites did not parasitise reticular cells of the spleen and bone marrow,
      in contrast to Plasmodium mexicanum as described in unnatural host species.
      Little difference was seen between two strains of P. sasai in its natural host T.
      tachydromoides and a strain isolated from Takydromus smaragdinus.

PMID- 9559366
TI  - Analysis of infraspecific variation among five strains of Eimeria maxima from
      North America.
AB  - Two laboratory strains from the eastern shore of Maryland 15 years ago and from
      an Ontario broiler house 23 years ago and three recent field strains of Eimeria
      maxima (isolated in Maryland, North Carolina and Florida) were examined for
      phenotypic and genotypic variation using protein profiles, random amplified
      polymorphic DNA-PCR analysis and DNA sequences obtained from the internal
      transcribed spacer regions of the rRNA genes. Staining profiles obtained by one
      dimensional SDS-PAGE of sporozoite proteins were identical in all five strains.
      Using random amplified polymorphic DNA-PCR analysis with high %G-C content
      decamers as primers, we were able to confirm that the five strains are all E.
      maxima, but were unable to discern any relationships among them because of the
      limited number of shared polymorphisms identified. In contrast, cloning and
      sequencing of the internal transcribed spacer-1, 5.8S rDNA and internal
      transcribed spacer-2 regions of the rRNA genes provided sufficient sequence
      information to infer phylogenetic relationships among the strains. Almost all of
      the infraspecific variation was located in the internal transcribed spacer
      regions. Only two base changes were identified within the 5.8S rRNA gene.
      Evolutionary relationships among the strains inferred using parsimony analysis of
      the aligned internal transcribed spacer sequences were well supported, but the
      hypothesised relationships did not correlate well with the demonstrated
      immunological cross-reactivities of these strains.

PMID- 9559367
TI  - Mitochondrial ND1 gene sequences used to identify echinostome isolates from
      Australia and New Zealand.
AB  - Echinostomes were collected in Australia and New Zealand as cercariae,
      metacercariae or adults. Using DNA sequences from the mitochondrial ND1 gene
      Echinostoma revolutum and Echinostoma paraensei were discovered in Australia. The
      presence of a further five, as yet unidentified, echinostome species was inferred
      in Northern Australia and a further isolate, closely allied to E. revolutum,
      occurs in New Zealand. ND1 sequences of species within the genus diverge from
      each other by 9.6-30.8%. Sequence divergence levels among strains within a single
      species are 0-3.6%. The phylogenetic tree produced from the Australasian
      isolates, in addition to species described previously, identifies the 37-collar
      spine species as a well supported monophyletic group. The five unidentified
      Australian species cluster away from the 37-collar-spine group. These
      unidentified species appear to divide further into > 37-collar-spine and < 37
      collar-spine clusters. Three strains of E. revolutum, collected as metacercariae
      from snails, were identified from two ponds located 6 km apart. Two of these
      strains may be cycling through a planorbid snail, Glyptophysa sp., as first
      intermediate host; however, this hypothesis could not be confirmed as specimens
      could not be obtained to match sequences between larvae and adults.

PMID- 9559368
TI  - Inheritance of levamisole and benzimidazole resistance in an isolate of
      Haemonchus contortus.
AB  - Reciprocal crosses between an isolate of Haemonchus contortus resistant to both
      benzimidazole and levamisole anthelmintics and a susceptible isolate were
      performed in order to determine the mode of inheritance of these resistances. F1
      and F2 generations and parent isolates were assayed for susceptibility to
      thiabendazole and levamisole in vitro. For each drug all of the filial
      generations were intermediate in susceptibility between the parent isolates, and
      analysis indicated that resistance was inherited as an incompletely recessive
      character determined by more than one gene in each case. There was no evidence of
      maternal inheritance. Results of both the in vitro assays and in vitro selection,
      followed by determination of sex ratio in the survivors, as well as studies on
      adult worms, provided no evidence for sex-linkage. This work illustrates that in
      vitro assays coupled with minimal studies in sheep are useful for determining
      inheritance of resistance, yet use fewer experimental animals than traditional
      studies.

PMID- 9559369
TI  - Chemo-orientation of echinostome cercariae towards their snail hosts: amino acids
      signal a low host-specificity.
AB  - The cercariae of Pseudechinoparyphium echinatum and Echinostoma revolutum
      approach their intermediate host snails by turning back when swimming in
      decreasing concentration gradients of snail conditioned water. Host stimuli are
      small molecular amino compounds, probably amino acids. This response was
      inhibited reversibly when the cercariae were treated with 0.45 microM-silver
      nitrate. As silver nitrate binds to the ciliated papillae of the cercarial
      surface, papillar chemoreceptors may be involved. Snail conditioned water from
      different snail species stimulated different intensities of chemo-orientation in
      both species of digeneans. However, when the samples of water conditioned with
      different snail species or even fish, tadpoles and leeches were diluted to the
      same total amino acid concentrations, the intensities of cercarial responses were
      similar. Therefore, some specificity of the chemo-orientation seemed to be
      achieved only by the total concentration of amino acids and not by particular
      mixtures of amino acids. In fact, amino acid spectra released by freshwater
      snails varied not only among different snail species, but also within the same
      species.

PMID- 9559370
TI  - Chemo-orientation of echinostome cercariae towards their snail hosts: the
      stimulating structure of amino acids and other attractants.
AB  - The cercariae of Pseudechinoparyphium echinatum and Echinostoma revolutum locate
      their host snails by turning back when swimming in decreasing gradients of the
      small molecular weight fraction (< 500) of snail conditioned water. Fractionation
      and chemical modifications of snail conditioned water from Lymnaea stagnalis
      showed that amino acids are necessary for the stimulating activity of snail
      conditioned water. A complete mixture of amino acids in concentrations determined
      from snail conditioned water had a high attraction. However, differently composed
      mixtures of amino acids and even single amino acids also had the same attraction
      as this complete mixture when used in concentrations corresponding to the total
      concentration of amino acids in snail conditioned water. Experiments with
      analogues and derivatives of amino acids showed that the primary alpha-amino
      group and the alpha-carboxyl group are necessary for the full effectiveness of
      amino acids. The highest effect was elicited by L-amino acids with a primary
      alpha-amino group, whereas the amino acid type and the chain length seemed to be
      unimportant. However, the full attraction of snail conditioned water was not
      achieved by amino acids alone. Chemical modifications of snail conditioned water
      suggested that the additional stimuli were neither inorganic ions nor organic
      acids or lipids. As the full attraction of snail conditioned water was obtained
      when the amino acid mixture of snail conditioned water was combined with its
      content of urea and ammonia, we conclude that the cercariae use only these
      excretory products as additional signals for their chemo-orientation. Chemo
      orientation to amino acids, urea and ammonia seems to reflect a strategy to
      locate a broad spectrum of aquatic hosts.

PMID- 9559371
TI  - Seroprevalence of antibodies to Neospora caninum and Toxoplasma gondii in water
      buffaloes (Bubalus bubalis) from Egypt.
AB  - Sera from 75 water buffaloes from Egypt were examined using a direct
      agglutination test incorporating mercaptoethanol for antibodies to Neospora
      caninum and Toxoplasma gondii. Antibodies to N. caninum were found in 51 (68%) of
      75 buffaloes in titres of 1:20 (six buffaloes), 1:40 (15 buffaloes), 1:160 (one
      buffalo), 1:320 (one buffalo) and > or = 1:640 (28 buffaloes), using N. caninum
      formalin-preserved whole tachyzoites as antigen. Antibodies to T. gondii were not
      found in a 1:100 dilution of serum of any of the 75 buffaloes, using T. gondii as
      antigen, indicating specificity in the detection of antibodies to N. caninum.
      This is the first report of N. caninum prevalence in water buffaloes, which are
      economically very important domestic animals in developing countries.

PMID- 9559372
TI  - An evolutionary definition of parasitism.

PMID- 9559373
TI  - Comparison of vessel diameters in electron beam tomography and quantitative
      coronary angiography.
AB  - Electron beam tomography (EBT) has been shown to permit non-invasive imaging of
      the coronary arteries after intravenous injection of contrast agent and 3
      dimensional reconstruction. We compared the vessel diameters in EBT
      reconstructions to quantitative coronary angiography (QCA). 10 patients were
      investigated by EBT and QCA. 3-dimensional EBT reconstructions (shaded surface
      display) were performed after acquisition of 40 axial cross-sections of the heart
      with 3 mm slice thickness (1 mm overlap) which were obtained triggered to the ECG
      in breathhold following intravenous injection of 120-160 ml of contrast agent. A
      fixed lower reconstruction threshold of 80 HU was used to selectively visualize
      the contrast-enhanced coronary artery lumen. At 60 sites in the coronary artery
      system, the vessel diameters measured in the EBT reconstructions were compared to
      the diameters found in quantitative analysis of the patients' coronary
      angiograms. The correlation coefficient of the vessel diameters in EBT and QCA
      was 0.83. Mean vessel diameters were not significantly different in EBT and QCA
      (3.06 +/- 0.93 vs. 2.97 +/- 0.94 mm). However, very small vessel diameters tended
      to be underestimated in the EBT reconstructions, which was due to the partial
      volume effect. It only vessel diameters measured in the left main or left
      anterior descending coronary artery were compared to QCA, the correlation
      increased to 0.87, since these vessel segments are less prone to artifacts in the
      EBT investigation. Vessel diameters in EBT and QCA correlated reasonably well.
      Due to partial volume effects, the diameter of very small vessels and stenotic
      segments tends to be underestimated by EBT.

PMID- 9559374
TI  - Smoking correlates with flow-mediated brachial artery vasoactivity but not cold
      pressor vasoactivity in men with coronary artery disease.
AB  - Impaired endothelial function is observed as altered vasomotion in both the
      peripheral and coronary circulation in the presence of cardiovascular risk
      factors and early atherogenesis. An improvement in endothelium-dependent
      vasoactivity has been reported with both cholesterol reduction and smoking
      cessation. This study was performed to determine whether smoking status in
      coronary artery disease (CAD) effects both flow-mediated and cold pressor
      vasoactivity. We studied 25 men (ages 30-59), 12 smokers and 13 nonsmokers with
      angiographically documented coronary artery disease and cardiac risk factors who
      were grouped as smokers and nonsmokers. Using 7.5 MHz ultrasound, we measured
      brachial artery diameter and Doppler flow velocity at baseline, following 5 mins
      of ipsilateral blood pressure cuff occlusion and release (flow-mediated), during
      contralateral ice water hand immersion (cold pressor test) and after sublinqual
      nitroglycerin administration (an endothelium-independent vasodilator). Flow
      mediated percent diameter change was significantly less in the smokers than
      nonsmokers (1.9 +/- 5.7% vs 11.4 +/- 7.2%, p < 0.001). Both smokers and
      nonsmokers responded similarly to the cold pressor test (-3.9 +/- 2.3 vs -1.2 +/-
      0.2%) and nitroglycerin (15.1 +/- 7.6 vs 17.5 +/- 8.3%). Cholesterol level did
      not appear to be an independent determinant of flow-mediated vasoactivity when
      smoking status was taken into account. Flow-mediated vasoactivity is associated
      with smoking status in the presence of coronary artery disease but cold pressor
      induced vasoactivity is not.

PMID- 9559375
TI  - An analogue laser optical disc in comparison with cinefilm for visual analysis of
      coronary narrowings before and after coronary angioplasty.
AB  - This study evaluated an analogue laser optical disc (MVP) as an alternative for
      cinefilm angiography in the visual analysis of coronary angiograms. Visual
      analysis was performed independently by 5 observers using cinefilm and MVP before
      and after PTCA (194 coronary lesions in 88 patients) and the outcomes were
      compared with QCA. The mean percentage diameter stenosis on cinefilm and MVP
      yielded similar results compared to QCA. Regression analysis showed a good
      correlation between the mean cinefilm and MVP values per diameter stenosis (p <
      0.001). Bland-Altman plots confirmed these findings. Qualitative analysis for
      detection of coronary dissections after PTCA showed an incidence of 31.3%
      (cinefilm) and 21.8% (MVP) (p < 0.05). The results of this study indicate that
      the visual analysis of the coronary angiograms using the analogue laser optical
      disc (MVP) yields similar results compared to the cinefilm concerning coronary
      lesion severity, although there is an underestimation of coronary dissections.

PMID- 9559376
TI  - Normal left ventricular volumes and ejection fraction: assessment with
      quantitative digital cardioangiography.
AB  - The aim of this study was to assess the accuracy and precision of a digital
      angiography system, the General Electric DX system, as compared to conventional
      left ventricular cineangiography. After a phantom study, sixty patients with
      normal coronary arteries and normal left ventricles (LV) were studied. The LV
      contours were manually traced from raw or subtracted digital runs and from the
      cine films in an independent manner. A regression formula was used to adjust the
      DX derived data to the cine film results (Vcorrected = 0.693 Vmeasured +8.65 ml).
      There was an excellent correlation between the two methods in the end-diastolic
      volume index (r = 0.97, sd = 4.2 ml/m2), the end-systolic volume index (r = 0.95,
      sd = 2.7 ml/m2), the stroke volume index (r = 0.93, sd = 4.1 ml/m2), and the
      ejection fraction (r = 0.85, sd = 3.45%). We conclude that manual tracing of LV
      contours from either raw or subtracted digital images provides reliable and
      accurate measurement of LV volume and ejection fraction.

PMID- 9559377
TI  - Contribution of long axis motion of left ventricular outflow to calculation of
      left ventricular stroke volume.
AB  - Stroke volume can be calculated by using noninvasive Doppler techniques. The
      products of pulsed Doppler stroke distance of left ventricular outflow and left
      ventricular outflow area can often be used to calculate stroke volume. However,
      left ventricular outflow also moves longitudinally toward the apex of the
      ventricle during systole, so that zero velocity flow cannot be detected by the
      usual pulsed Doppler studies. We evaluated the contribution of these zero
      velocity flow to the noninvasive estimation of left ventricular stroke volume in
      20 patients with left ventricular disease and in 20 age matched healthy controls.
      Left ventricular stroke distance was calculated by summing the Doppler stroke
      distance and the outflow long axis motion. The percentage of zero velocity flow
      for total stroke volume was calculated in each group. Cardiac output was also
      measured by thermo-dilution technique. The percentage of zero velocity flow for
      total noninvasive stroke volume in patients with left ventricular disease was 2.5
      +/- 1.1 ml (4.0 +/- 1.5%), significantly lower than in normal subjects, 3.6 +/-
      1.0 ml (5.5 +/- 1.5%) (p < 0.05). These long axis motions are significantly
      reduced, especially in left ventricular disease. Amplitudes of the left
      ventricular outflow long axis motion were correlated with Doppler stroke distance
      in all (r = 0.54, p < 0.01). In patients with myocardial infarction, stroke
      volume by thermo-dilution methods and calculated stroke volume showed good
      correlation both only by Doppler stroke distance (y = 1.044x + 0.547, r = 0.968)
      and by Doppler and long axis motion (y = 0.989x + 0.521, r = 0.974). Compared
      with stroke volume measured by thermodilution method, stroke volume calculated
      only by Doppler stroke distance was underestimated. We thus demonstrated the
      influence of zero velocity flow on left ventricular outflow both in patients with
      left ventricular disease and in normal subjects.

PMID- 9559378
TI  - Left atrial function in congestive heart failure: assessment by transmitral and
      pulmonary vein Doppler.
AB  - The relation of transmitral flow patterns and pulmonary venous velocities was
      analyzed from 50 heart failure patients (28 men, 22 women; mean [+/- SD] age 61
      +/- 9 years) with a left ventricular ejection fraction < 40%. Doppler
      echocardiography was performed in all patients. Transmitral flow measurements
      included early (E) and atrial (A) velocities and deceleration time of E wave
      (DT). Patients were assigned to two groups according to E/A ratio, DT, or both:
      20 patients in the restrictive group, and 30 patients in the nonrestrictive
      group. Pulmonary venous flow was obtained by the transthoracic approach. Systolic
      (S), diastolic (D) and atrial reversal (Ar) velocities were measured. Of the
      study population, 13 patients had simultaneously determined pulmonary capillary
      wedge pressure (PCWP). The results showed a lower S (28 +/- 11 vs. 51 +/- 10
      cm/sec, p < 0.01), a higher D (66 +/- 13 vs. 44 +/- 10 cm/sec, p < 0.01) and a
      smaller Ar (12 +/- 10 vs. 24 +/- 9 cm/sec, p < 0.01) in the restrictive group
      compared with those in nonrestrictive group. In the subgroup of patients
      undergoing invasive hemodynamic studies, there was no relationship between PCWP
      and atrial reversal velocity. However, a significant correlation was observed for
      pulmonary systolic (r = -0.70, p < 0.01) and diastolic (r = 0.76, p < 0.01)
      velocities to PCWP. These findings suggest a reduction in left atrial compliance
      and atrial systolic function and both play important roles in heart failure
      patients with the restrictive transmitral flow pattern.

PMID- 9559379
TI  - Left ventricular volumes assessed by different new three-dimensional
      echocardiographic methods and ordinary biplane technique.
AB  - Three-dimensional (3D) echocardiography may overcome the problems with inadequate
      accuracy and reproducibility of 2D volume measurements of the left ventricle.
      AIMS: To establish the in vitro accuracy and reproducibility of two new methods
      for 3D echocardiographic volume determination as compared to biplane
      measurements. METHODS: Validation of volume measurements by a multiplane 3D
      method was performed on asymmetric latex phantoms (n = 8, true volumes 45-304 ml)
      using rotational acquisition of 90 image planes. Porcine agarose-filled
      asymmetrical left ventricles (n = 7, true volumes 34-280 ml) were measured by the
      same multiplane 3D method based on images acquired by probe rotation axis
      perpendicular (A) and parallel (B) to the ventricular long axis. Ventricular
      volumes were also obtained by a simplified 3D system using only the three
      standard apical views (C) and by the ordinary biplane Simpson's method (D).
      RESULTS: On latex phantoms systematic deviation from true volumes by multiplane
      3D was less than 2%, and 95% variability of individual measurements from this
      mean was +/- 4.9%. For accuracy on left ventricles, systematic bias was small
      with all the methods (< 5%), but 95% variability of individual measurements was
      +/- 9.0%, 15.4%, 18.8% and 41.3% of true volumes for methods A-D respectively.
      Corresponding results in the same range were obtained for inter- and
      intraobserver variability. CONCLUSION: Individual in vitro volume estimates of
      left ventricles are of similar quality using apical multiplane or apical triplane
      3D echocardiography. Both methods were superior to the ordinary apical biplane
      method, but inferior to multiplane 3D method with the probe directed
      perpendicular to the ventricular long axis.

PMID- 9559380
TI  - In vitro examination of the coronary artery wall after balloon angioplasty using
      intracoronary ultrasound.
AB  - After autopsy 12 human coronary arteries were investigated by intracoronary
      ultrasound in order to measure the vessel wall dimensions and to detect damage on
      the vessel wall architecture after balloon angioplasty. Histology revealed
      artherosclerosis in 11/12 arteries. A total of 41 representative coronary
      segments were selected for further off-line ultrasound and histological analysis.
      Intracoronary ultrasound and histological measurements of the vessel wall
      thickness after balloon dilatation demonstrated a good correlation between the
      maximum thickness of the intima (histology 0.62 mm vs. intracoronary ultrasound
      0.65 mm, r = 0.87) and the intima-media complex (0.80 mm vs. 0.83 mm, r = 0.87),
      in contrast to a weak one between the minimum thickness (r = 0.46 and r = 0.37).
      A total of 21 cases of damage occurred during angioplasty; intracoronary
      ultrasound detected 17. Further analysis showed that it imaged 10 of 11 cases of
      damage involving more than 30 degrees of the vessel circumference and 7 of 10
      cases of damage involving less than 30 degrees of the vessel circumference. After
      balloon angioplasty of diseased coronary arteries, intracoronary ultrasound is
      therefore reliable in measuring the maximum wall thickness and in imaging damage
      involving more than 30 degrees of the vessel wall circumference.

PMID- 9559381
TI  - Differences in pain assessment and decisions regarding the administration of
      analgesics between novices, intermediates and experts in pediatric nursing.
AB  - This article describes a study examining the influence of expertise on nurses'
      pain assessments and decisions regarding pharmacological interventions in
      children. In an experimental design, novices (n = 271), intermediates (n = 222),
      and experts (n = 202) in pediatric nursing, various cases were presented. Each
      case consisted of a combination of a vignette and a video. Subjects were asked
      (1) to assess the child's pain intensity, (2) to specify their confidence in the
      assessment, and (3) to state whether or not they would administer a non-narcotic
      analgesic. The results indicated that expertise did not influence assessments of
      pain intensity. However, expertise did have a distinct impact on both the
      subjects' confidence in their decisions, and the decision to administer
      analgesics. Experienced nurses were most confident and were most inclined to
      administer analgesics. The findings of this study are placed in the context of a
      general theory on the development of expertise, which assumes that experts'
      decision-making is based on cognitive structures that describe features of
      prototypical or even actual patients, so called "illness scripts". From this
      theory it can be deduced that mainly practical experience is responsible for the
      (lack of) differences in decision-making between novices, intermediates and
      experts.

PMID- 9559382
TI  - Student nurses perceptions of their interpersonal skills: a re-examination of
      Burnard and Morrison's findings.
AB  - Heron's six category intervention analysis is a component of many counselling
      courses and is used extensively by teachers of interpersonal skills within
      nursing curricula. The popularity of this framework has generated a number of
      studies which have attempted to offer empirical support for the theory. The aim
      of this study was to re-evaluate some of these findings. Utilising an earlier
      research instrument, a set of findings are offered and comparisons made with
      previous work. Our findings suggest that student nurses perceive themselves to be
      most skilled in the use of supportive, prescriptive and cathartic interventions
      and least skilled in the use of informative, catalytic and confronting
      interventions. A discussion of the new findings and their implications is
      offered.

PMID- 9559383
TI  - Humor in nursing practice: a phenomenological study.
AB  - Humor is an important but underutilized resource in nurse-patient interaction.
      The multidimensional value of humor in providing nursing care has recently begun
      to receive attention. The purpose of this phenomenological study was to describe
      the meaning of nurses' use of humor in their nursing practice. Twenty-one
      registered nurses enrolled in a graduate nursing program described in detail an
      experience they had using humor in providing nursing care. The 21 written
      descriptions were analyzed using Colaizzi's phenomenological method. Five themes
      emerged in which humor was found to (a) help nurses deal effectively with
      difficult situations and difficult patients, (b) create a sense of cohesiveness
      between nurses and their patients and also among the nurses themselves, (c) be an
      effective therapeutic communication technique that helped to decrease patients'
      anxiety, depression, and embarrassment, (d) be planned and routine or be
      unexpected and spontaneous, and (e) create lasting effects beyond the immediate
      moment for both nurses and patients.

PMID- 9559384
TI  - Quality of STD care in an urban Zambian setting: the providers' perspective.
AB  - The aim of this paper is to analyse obstacles to optimal STD care in an urban
      setting in Zambia. Eight-two health professionals answered a questionnaire with
      closed and open-ended questions. More than 50% were not satisfied with their
      working conditions, due to heavy workload, lack of equipment/drugs, poor salary,
      and lack of continuing education. Negative opinions about STD patients were
      common. Treatment and preventive activities were considered important but most
      respondents found patient compliance poor--especially for partner notification.
      To improve the quality of STD care, training in STD management should be combined
      with improved working conditions.

PMID- 9559385
TI  - Coping strategies of enrolled nurses in nursing homes: shifting between
      organizational imperatives and residents' needs.
AB  - In today's nursing homes, which can be considered modern versions of "total
      institutions", enrolled nurses expend much energy coping with problems which
      arise from the day-to-day care of seriously impaired patients. The problems they
      encounter include the burden of never ending work, having to cope with deviant
      and problematic behaviour, handling emotional disturbance and, on a more abstract
      level, balancing self-interest and power with love and affection. The grounded
      theory approach was used to discover the coping strategies employed by enrolled
      nurses. On the criterium of favouring either organizational imperatives or
      residents' needs, six strategies were differentiated, and placed into one of two
      categories. The discovery during research of two distinct nursing teams, each
      inclining towards the strategies available within one of these two categories,
      not only has important theoretical implications, but also practical consequences
      for the training of student nurses, the labour market and the quality of care.

PMID- 9559386
TI  - Pharmacist and nurse: a team approach towards primary health care or a convenient
      "therapeutic alliance"?
AB  - This paper explores the nature of the therapeutic alliance between nurses and
      community pharmacists in the South African context. To gain a better insight into
      the relatively new phenomenon, a combination of qualitative and quantitative
      methods was employed. The partnership developed in S.A. between the nurse and the
      pharmacist allows the pharmacists to "expand" their professional activities
      without "invading" the nurses' professional domain, and reaping substantial
      benefits in the process. These include potential increases in profits, enlarging
      the clientele base and improving the image of the pharmacy, by shifting the focus
      from a place of disease to a place of health, as well as creating the vision of
      the pharmacist as a team member in providing primary health care. As far as the
      nurses are concerned, it grants them the possibility to practice their profession
      in a very convenient set-up and affords them greater professional autonomy.

PMID- 9559387
TI  - Testing a model of absence and intent to stay in employment: a study of
      registered nurses in Malta.
AB  - This study used a cross-sectional, correlational design to test a model of
      absence and turnover of registered nurses developed from a review of the research
      literature (Gauci Borda and Norman, 1997). Testing the model involved comparing
      the relationship between job satisfaction, kinship responsibility, pay,
      employment opportunity, intent to stay in employment and absence for male and
      female registered nurses. All registered nurses (n = 254) working in clinical
      areas on a full-time shift basis, in one large general hospital in Malta were
      surveyed by questionnaire and their absence data were obtained from the hospital
      personnel records. A response rate of 67% (n = 171) was achieved. The results
      showed that nurses were satisfied with their job and intended to stay in their
      present employment for the next 12 months. Relationships between variables
      differed between male and female nurses, with job satisfaction being associated
      with intent to stay for male nurses but not for females and kinship
      responsibility and intent to stay being associated with absence in female but not
      male nurses. In contrast to many previous studies of nurses, an association was
      found between job satisfaction and absence. Several variables, including fear of
      change, which may influence intent to stay of Maltese nurses, were identified.
      The proposed model of absence and turnover stood up reasonably well to testing,
      but the results for the whole sample, and the sub-samples of male and female
      nurses supported different parts of the model. The main implication for future
      research is that male and female nurses should be studied separately due to
      differences found between the two groups.

PMID- 9559388
TI  - Factors influencing turnover and absence of nurses: a research review.
AB  - This review of the nursing literature aims to identify the factors with the
      greatest influence on turnover and absence of qualified nurses, possible common
      factors influencing both, and the relationship between absence and turnover. A
      hypothetical model grounded in the literature which depicts the expected
      relationships between these variables is presented for testing in an empirical
      study. The review identifies intent to stay in current employment as the variable
      with the greatest influence on turnover. Intent to stay is in turn most strongly
      associated with job satisfaction. Other variables are identified by single
      studies as having an influence on intent to stay, but are not supported by the
      results of other studies; exceptions are pay, opportunity for alternative
      employment and kinship responsibility, which are supported by the results of two
      studies. The relationship between job satisfaction and absence is unclear and
      requires further investigation. However, job satisfaction is identified as
      possibly influencing both absence and intent to stay and kinship responsibility
      is identified as a common antecedent of absence and intent to stay. Similarly,
      absence is identified as an antecedent to turnover. Thus, it is expected that
      absence would be positively related to turnover and negatively related to intent
      to stay. Understanding such relationships should allow identification of
      management strategies to reduce both turnover and absence.

PMID- 9559389
TI  - Fishing for understanding: nurses knowledge and attitudes in relation to
      nutritional care.
AB  - Many studies have demonstrated that malnutrition is a significant problem amongst
      hospital patients, but little is known about what nurses actually do, and what
      factors influence this. This study aimed to explore the nutritional attitudes,
      knowledge base and nursing care of qualified nurses in an acute hospital. A
      survey of nurses' records for documented nutrition related activities was carried
      out for all (141) patients from five wards for two weeks, followed by a
      questionnaire, focused on nutrition-related attitudes, activities and knowledge,
      to all qualified nurses of these and a further four wards (110 nurses). Results
      revealed evidence of some knowledgeable and pro-active attitudes and nursing
      care; however, there was little association between knowledge, stated attitudes
      and behaviour and discrepancies were observed between questionnaire responses and
      documented activities. Ajzen and Fishbein's (1980) theory relating beliefs,
      attitudes, intentions and behaviour was not supported although this might be
      attributed, in part at least, to nurses not regarding weighing patients as
      nutritional assessment. Behaviour appeared to have been influenced by a variety
      of factors and relationships between attitudes, knowledge and activities seemed
      far from straightforward.

PMID- 9559390
TI  - Feeding difficulty in elderly patients with dementia: confirmatory factor
      analysis.
AB  - The latent structure of feeding difficulty in elderly patients with dementia was
      investigated using multivariate statistical techniques including exploratory and
      confirmatory factor analysis. A survey design of 345 elderly patients with the
      diagnosis of dementia using a questionnaire completed by key workers and primary
      nurses, was used in local psychogeriatric and continuing care of the elderly
      facilities. Feeding difficulty and nursing intervention were estimated followed
      by fitting of latent variable models of feeding difficulty to the data using
      structural equation modelling. Three models of feeding difficulty in elderly
      patients with dementia, with 2, 3 and 4 factor structures respectively were
      compared. All three models showed a good fit to the data as assessed by several
      standard criteria. The 3 and 4 factor models, however, showed significantly
      better fit than the 2 factor model. The 4 factor model introduced a latent
      variable of "oral difficulty" with feeding which merits further investigation.
      This study demonstrates the possibility of developing reliable and validated
      scales for the assessment of feeding difficulty in elderly patients with
      dementia.

PMID- 9559391
TI  - The helping relationship in the community setting: the relevance of Rogerian
      theory to the supervision of Project 2000 students.
AB  - A series of twenty-six interviews, fourteen with district nursing sisters and
      twelve with students they supervised, was conducted in 1992 in one Project 2000
      demonstration district in England. The data were collected as part of an English
      National Board funded research study; data were reinterpreted in 1994 and formed
      one element in the author's PhD thesis. Participants described the ways in which
      a supervisor might enable a student to learn during a community placement. One of
      the most important means by which supervisors could provide assistance was by
      creating an environment in which the students felt supported. Students described
      how supervisors demonstrated concern, acceptance and understanding, attributes
      which bore striking resemblance to the qualities of congruence, unconditional
      positive regard and empathic understanding identified by Carl Rogers as enabling
      learning.

PMID- 9559392
TI  - Support and coping of male hemodialysis-dependent patients.
AB  - The purpose of this descriptive-correlational study was to describe coping
      strategies used by males with chronic renal failure who are dependent on
      hemodialysis; to describe their social networks; to describe the perceived
      support, conflict, and reciprocity within their interpersonal relationships; and
      to examine the relationships among the variables support, conflict, reciprocity,
      social networks, and coping strategies. Social support was conceptualized as a
      coping resource or source of assistance in coping with the renal illness- or
      hemodialysis-related stressor. The Ways of Coping questionnaire and the
      Interpersonal Relationship Inventory were administered to 30 participants while
      in hospital. Although, both problem-focused and emotion-focused forms of coping
      were used, participants primarily used problem-focused coping, in particular,
      "seeking social support". Overall, the participants perceived relatively high
      levels of support and moderate to high levels of reciprocity with members of
      their social networks. Participants experienced a moderate level of conflict in
      their interpersonal relationships. Both escape-avoidance and conflict were
      positively associated with the number of people in the household. Positive
      reappraisal was negatively associated with the number of close relatives. The
      small sample size prohibits generalizability of the results. Longitudinal studies
      with a larger randomly selected sample would yield insights into the long-term
      psychological outcomes of different coping strategies and into the bi-directional
      relationship of support from social network and coping in this population.
      Implications for nurses are discussed.

PMID- 9559393
TI  - Theory and research: a linkage to benefit practice.
AB  - This paper begins with a critical overview of what the extant literature sees as
      the relationship between research, theory and practice. Most scholars maintain
      that there are two main viewpoints: research exists to build theory from practice
      and/or research exists to test existing theory in practice. It will be argued
      that is too simplistic a view and four specific linkages will be proffered:
      Theory Testing Research, Theory Generating Research, Theory Evaluating Research
      and Theory Framed Research. All four will be discussed and their contribution to
      the knowledge base of nursing practice explored. In concluding, an argument will
      be put forward proposing the view that undertaking research without considering
      theory is an empty and non-productive exercise.

PMID- 9559394
TI  - Attitudes of Asian and American graduate nursing students towards death and
      dying.
AB  - This study compared the difference in attitudes towards death and dying between
      17 Asian and 11 American graduate nursing students. Asian and American students
      did not significantly differ in attitudes related to fear of death, of self, or
      others, but Asian students were significantly more afraid than American students
      of their own process of dying. Asian students were more averse than American
      students to interacting and discussing death with dying patients. Talking about
      death with dying patients was the most difficult aspect of care for both groups.
      However, Asian students gained more personal satisfaction than American students
      in caring for dying patients. The findings provoke discussion regarding
      differences in nursing practice by Asian and American graduate nursing students.

PMID- 9559395
TI  - Tuberculin surveys--why?

PMID- 9559396
TI  - Fluoroquinolones: a new treatment for tuberculosis?
AB  - The fluoroquinolones have secured an important place in the management of
      bacterial infection, they are well absorbed orally, are found in respiratory
      secretions in higher concentrations than in serum and are concentrated inside
      macrophages. The agents are well tolerated and have an excellent safety record in
      long-term therapy. No new antituberculosis agents have been developed since the
      introduction of rifampicin into clinical use, so fluoroquinolones have been
      investigated for potential efficacy in tuberculosis. In vitro studies have shown
      that they are active against Mycobacterium tuberculosis at achievable
      concentrations. Treatment studies in mice have demonstrated efficacy. Few
      clinical studies have been performed in humans, but ciprofloxacin has
      demonstrated significant early bactericidal activity. Regimens including a
      fluoroquinolone have been comparable to other standard regimens, although the
      outcome in human immunodeficiency virus (HIV) seropositive patients was
      significantly poorer. There is still insufficient clinical data to use
      fluoroquinolones in first-line treatment of tuberculosis, but they may find a
      role in the management of multidrug-resistant infections or in patients with
      adverse reactions to other agents.

PMID- 9559397
TI  - National tuberculin survey of Kenya, 1986-1990.
AB  - SETTING: The first tuberculin survey conducted in Kenya by the World Health
      Organisation in 1958-1959 found an annual risk of tuberculosis infection (ARTI)
      of 2.5%. OBJECTIVE: To estimate the ARTI and its trend in recent years and to
      compare the estimated incidence rates with the notification rates. DESIGN: A
      tuberculin survey was held in 12 randomly selected districts in the period 1986
      1990. Tuberculin testing with 2TU PPD RT 23 + Tween 80 was performed in 40,365
      primary schoolchildren aged 6-13. RESULTS: Of 14,984 non BCG-vaccinated children,
      1,380 (9.2%) had indurations of > or = 10 mm. Double testing with PPD RT 23 and
      PPD-scrofulaceum in 980 non BCG-vaccinated children revealed a high level of
      infections due to mycobacteria other than tuberculosis (MOTT). Therefore, the
      prevalence of tuberculous infection was based on the sum of 50% of the
      indurations of 17 mm and all indurations of 18 mm or more multiplied by two. The
      prevalence of tuberculous infection in schoolchildren aged on average 8.4 years,
      'weighted' for the population size according to the provisional results of the
      1989 census, was calculated at 5.5%. The corresponding ARTI is 0.6%. CONCLUSION:
      The ARTI has declined by an average 4.6% per year. The tuberculosis problem
      differs from one area to the next, with the highest prevalences of infection on
      the coast and in Eastern Kenya, and the lowest in Western Kenya. Although the
      average ratio of observed and estimated incidences indicate that 70% of incident
      cases are notified, considerable inter-district variations are observed.

PMID- 9559398
TI  - The molecular epidemiology of tuberculosis in Zaragoza, Spain: a retrospective
      epidemiological study in 1993.
AB  - SETTING: The incidence of tuberculosis (TB) in Spain is one of the highest in
      Europe. In Zaragoza region the incidence rate of tuberculosis and the acquired
      immune deficiency syndrome (AIDS) are close to the national average. OBJECTIVE:
      To better define the molecular epidemiology of tuberculosis in an area of Europe
      where this has not been previously studied. DESIGN: A retrospective
      epidemiological study on tuberculosis was conducted in Zaragoza, a region of
      Spain, in 1993. The study population consisted of 226 patients from whom positive
      culture and complete clinical and demographic data were available. Mycobacterium
      tuberculosis strains were typed by standard restriction fragment length
      polymorphism (RFLP). A cluster was defined as two or more isolates with identical
      RFLP patterns when five or more copies of IS6110 are present. The 137 non
      clustered patients were compared with the 89 clustered patients and studied by
      using univariate analysis. RESULTS: Thirty-nine percent of the patients were
      clustered, suggesting possible recent transmission. Infection with drug-resistant
      M. tuberculosis was associated with a decreased risk of being in a cluster. The
      strains isolated from human immunodeficiency virus (HIV)-positive patients were
      not associated with clustering. We found that immigration was not a major
      determinant in the total number of TB cases. CONCLUSION: Immigration, HIV and
      drug resistance were not associated with recent transmission. More than 50% of
      the clusters contained two or three patients, indicating that small outbreaks
      were responsible for most of the tuberculosis cases. Our RFLP typing results
      indicate that a TB control programme should be implemented in Spain in order to
      lower transmission of TB.

PMID- 9559399
TI  - Nationwide surveillance of drug-resistant tuberculosis in The Netherlands: rates,
      risk factors and treatment outcome.
AB  - SETTING: The Netherlands, 1993 and 1994. OBJECTIVE: To determine 1) rates of drug
      resistance in relation to nationality and country of birth, 2) risk factors for
      drug resistance, 3) treatment outcome of drug-resistant cases, and 4) rates of
      primary and acquired drug resistance. DESIGN: Retrospective study of all cases
      notified with bacillary tuberculosis in The Netherlands in 1993 and 1994.
      RESULTS: Drug resistance to one or more drugs was reported in 268 (14.6%) of all
      1836 cases, of whom 203 (76%) were foreign born. In Dutch patients rates of
      isoniazid (H) (2.9%) and streptomycin resistance (3.6%) were lower than in
      foreign patients (8.6% and 10.6% respectively, P < 0.001). Multidrug (H and
      rifampicin [R]) resistance was reported in 0.5% of Dutch-born and 1.4% of foreign
      cases (P = 0.055). Rates of acquired resistance to H (11.4%) and HR (5.7%) were
      higher than rates of primary resistance to these drugs (5.2% and 0.7%
      respectively, P < 0.05), but the number of retreatment cases was low (6.8% of all
      cases). Drug resistance was associated with immigration but not with drug use,
      homelessness or human immunodeficiency virus (HIV) co-infection. One fifth (20%)
      of drug-resistant cases was diagnosed by active case finding. Treatment outcome
      in sensitive and resistant cases was compared. CONCLUSION: These findings suggest
      that drug resistance is imported, but it is unclear to what extent drug
      resistance among foreigners has been transmitted or created in The Netherlands.
      Drug resistance data should be monitored in Dutch and foreign patients
      separately.

PMID- 9559400
TI  - Origin and management of primary and acquired drug-resistant tuberculosis in The
      Netherlands: the truth behind the rates.
AB  - SETTING: The Netherlands, May 1994 to May 1996. OBJECTIVE: 1) To estimate to what
      extent drug-resistant tuberculosis was acquired or recently transmitted in The
      Netherlands, 2) to assess the relevance of drug resistance data as routinely
      collected, and 3) to describe case management. DESIGN: Prospective descriptive
      study. Patients diagnosed with drug-resistant tuberculosis were interviewed.
      Information on patient management and contact tracing was collected. IS6110
      restriction fragment length polymorphism (RFLP) patterns of all strains were
      compared with those of the National RFLP library and clusters were analyzed.
      RESULTS: In total 193 cases were included in the study. Acquired drug resistance
      (ADR) was rare. Dutch ADR patients reported receiving treatment a long time
      previously (mean age 58, mean treatment interval 23 years). Most foreign ADR
      patients had been treated recently in their country of origin. Of 151 primary
      drug-resistant (PDR) cases, 129 (85%) were foreign-born, of whom few (8%-19%) had
      been infected in The Netherlands. Few Dutch PDR cases had been infected recently
      (mean age 49 years). Rifampicin resistance was more frequently observed in
      foreign ADR cases than in foreign PDR cases (28% vs 5%; P < 0.001). One third of
      cases had not been treated according to treatment guidelines. CONCLUSION: Only a
      small proportion of drug-resistant cases resulted from recent infection or
      treatment in The Netherlands. General rates of ADR and PDR do not reflect current
      Dutch programme performance. For programme monitoring, ADR/PDR rates and their
      trends must be reported and evaluated in Dutch and foreign patients separately.

PMID- 9559401
TI  - Drug-resistant tuberculosis in human immunodeficiency virus infected persons in
      Italy. The Italian Drug-Resistant Tuberculosis Study Group.
AB  - OBJECTIVE: To describe the prevalence and epidemiological-clinical
      characteristics of tuberculosis (TB) resistance to first-line drugs in Italian
      human immunodeficiency virus (HIV)-infected subjects. DESIGN: Prospective,
      observational multicenter (25 Centers of Infectious Diseases) study.
      Mycobacterium tuberculosis strains from 167 HIV co-infected subjects with TB (149
      new cases, 18 relapses) were tested at a central laboratory for susceptibility to
      rifampin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E) and streptomycin
      (S) and for DNA fingerprint type. Drug susceptibility results were related to
      patients' epidemiological, clinical and laboratory features. RESULTS: Drug
      resistance patterns among new TB cases were as follows: R = 1%, Z = 6%, S = 8%, H
      + S = 3%, S + Z = 4%. TB resistant to at least R + H (MDR-TB) was detected in 36%
      of new cases due to an MDR-TB outbreak which was the largest thus far in Europe,
      involving 7/25 participating institutions, and was demonstrated by conventional
      and molecular epidemiology evidence. With multivariate analysis, MDR-TB was
      associated with hospital exposure to MDR-TB (OR = 39.3, P < 0.001) and previous
      use of anti-TB drugs (OR = 9.8, P = 0.008). CONCLUSION: As drug-resistant
      tuberculosis in Italy is thus far relatively scarce, detection of a large MDR-TB
      epidemic among HIV-infected subjects was alarming. Aggressive control measures
      are urgently needed to prevent the spread of MDR-TB throughout the country and
      among the general population.

PMID- 9559402
TI  - The bacteriology of pulmonary tuberculosis in a population with high human
      immunodeficiency virus seroprevalence.
AB  - SETTING: A public sector urban university hospital in Soweto, South Africa.
      OBJECTIVE: To describe the utility of sputum smear microscopy and the prevalence
      of Mycobacterium tuberculosis resistance to antituberculosis drugs according to
      human immunodeficiency virus (HIV) serostatus in adults. DESIGN: A retrospective
      descriptive study of consecutive cases using a record review. RESULTS: We studied
      412 adults with culture-proven pulmonary tuberculosis, of whom 185 (44.9%) were
      HIV-seropositive and had a significantly lower sputum smear positivity than HIV
      seronegatives (68% versus 79%, P < 0.05). Smear positivity was significantly
      higher in HIV-infected patients with CD4 counts < or = 50/mm3 compared to those
      with CD4 counts of 201-300/mm3 (P < 0.05). In patients with and those without a
      history of previous treatment for tuberculosis, resistance to one or more
      antituberculosis drugs was found in 32.2% and 13.6% of cases, respectively, while
      resistance to both isoniazid and rifampicin (multidrug-resistant tuberculosis
      [MDR]) was found in 15.3% and 4.5% of patients, respectively. There was no
      significant difference in resistance between HIV-positive and seronegative
      patients. CONCLUSION: A strong tuberculosis control programme and good
      surveillance will be required to prevent the further spread of MDR tuberculosis.
      Surveys such as these are useful for monitoring control programmes.

PMID- 9559403
TI  - Lack of direct correlation between CD4 T-lymphocyte counts and induration sizes
      of the tuberculin skin test in human immunodeficiency virus type 1 seropositive
      patients.
AB  - SETTING: The study was conducted in Bobo-Dioulasso, Burkina Faso, where
      Mycobacterium tuberculosis infection and human immunodeficiency virus type 1 (HIV
      1) infection are prevalent. OBJECTIVE: To identify proportions of representative
      (test) populations who are reactive to the tuberculin skin test, and to study the
      relationship between CD4 T-lymphocyte counts and the induration size of the
      tuberculin skin test in these groups. DESIGN: A group of 435 healthy students was
      tuberculin skin tested in order to evaluate the intensity of skin testing in a
      'normal' population. The study group consisted of 195 subjects with or without
      tuberculosis, and with or without HIV-1 infection, who received a tuberculin skin
      test and a CD4 T lymphocyte count on the same day. RESULTS: In total, 90% of the
      control (nontuberculous, HIV negative) subjects, 32% of the HIV-1 seropositive
      subjects, 76.5% of the tuberculous patients and 57% of the tuberculous HIV-1
      seropositive patients were tuberculin positive. There was no direct correlation
      between the induration size of reactions to the tuberculin skin test and CD4 T
      lymphocyte count in these study groups using linear regression analysis.
      CONCLUSION: In vivo skin testing using tuberculin yields clinically significant
      information on the degree of immunodeficiency which is different from that of CD4
      T-lymphocyte counts. The tuberculin skin test should therefore be used as an
      independent marker of the weakened immunological status of HIV-1 seropositive
      subjects.

PMID- 9559404
TI  - Tuberculosis patients and practitioners in private clinics in India.
AB  - SETTING: Rural and urban areas of Maharashtra, a large state in Western India.
      OBJECTIVE: To understand tuberculosis (TB) management practices among private
      medical practitioners (PPs) and the treatment behaviour of the patients they
      manage. DESIGN: Prospective study of help-seeking patterns and treatment
      behaviour among 173 pulmonary TB patients diagnosed in private clinics, and the
      TB management practices of 122 PPs treating these patients. RESULTS: The first
      source of help for 86% of patients was a PP. The diagnostic and treatment
      practices of PPs were inadequate; 15% did not consider sputum examination to be
      necessary, and 79 different treatment regimens were prescribed by 105 reporting
      PPs. Sixty-seven percent of the patients diagnosed in private clinics remained
      with the private sector, and the rest shifted to public health services within
      six months of treatment. The treatment adherence rate among the patients in
      private clinics was 59%. There were discrepancies between the reported management
      practices of the PPs and what their patients actually followed. CONCLUSION: The
      study identifies and highlights the need to educate PPs and their TB patients,
      and indicates ways in which PPs could be meaningfully involved in efforts to
      revitalize the national TB control programme.

PMID- 9559405
TI  - Bronchial asthma in two chemical fertilizer producing factories in eastern Saudi
      Arabia.
AB  - SETTING: Two urea fertilizer producing factories in Saudi Arabia. OBJECTIVE: To
      determine the prevalence of respiratory symptoms and diseases in employees
      exposed to ammonia gas. DESIGN: A cross-sectional study involving 161 exposed
      subjects and 355 controls. All completed a respiratory symptoms questionnaire,
      with additional questions on present and past occupations. Ammonia concentrations
      were measured in the different sections of the factories. RESULTS: The ammonia
      levels in factory B were well below the threshold limit value (TLV) (range 0.02
      7.0 mg/m3 of air). In factory A the range was 2.0-130.4 mg/m3. The control and
      exposed groups were comparable with respect to their smoking habits. The exposed
      subjects in factory A had significantly higher relative risks (RR) for all
      respiratory symptoms; the same was true for haemoptysis (RR: 4.1, 95% confidence
      interval: 1.63-10.28). Bronchial asthma, chronic bronchitis, and a combined
      diagnosis were significantly higher among those exposed to high cumulative
      ammonia levels. However, in the logistic regression analysis ammonia
      concentration was significantly related to cough, phlegm, shortness of breath
      with wheezing and bronchial asthma. CONCLUSION: Exposure to ammonia gas in the
      workplace is significantly associated with increase in respiratory symptoms and
      bronchial asthma. Re-engineering measures to lower the levels of ammonia in
      factory A are strongly recommended. The affected employees should be removed from
      further exposure and followed up.

PMID- 9559406
TI  - Implementing tuberculosis control programmes in Kaduna State, Nigeria.
AB  - This paper discusses the impact of pre-payment versus free drug therapy on case
      finding and treatment of tuberculosis patients. While the Kaduna State
      tuberculosis pilot project introduced fees mainly as a cost-recovery measure,
      evaluation of several cohorts revealed that while it led to a reduction in the
      proportion of diagnosed smear-positive patients that could afford treatment, it
      markedly enhanced compliance in those willing to pay. Ways to balance this trade
      off are suggested.

PMID- 9559408
TI  - Tuberculosis due to drug-resistant Mycobacterium bovis in pregnancy.
AB  - We describe the management practices adopted in a case of pulmonary and extra
      pulmonary tuberculosis caused by an isoniazid/pyrazinamide resistant strain of
      Mycobacterium bovis in a 26-week pregnant woman. She was initially treated with
      rifampin, isoniazid and ethambutol, pre-term delivery was induced and
      streptomycin was then added to the regimen. Screening of the new-born revealed no
      signs of either disease or infection. Isoniazid prophylaxis was not administered
      and the new-born was vaccinated and isolated from the mother for two months;
      however she continued to be fed with her mother's milk for the whole period.

PMID- 9559407
TI  - Polymerase chain reaction of pleural biopsy specimens for rapid diagnosis of
      tuberculous pleuritis.
AB  - SETTING: Government-administered regional teaching hospital. OBJECTIVE: To
      improve timeliness and sensitivity of laboratory diagnosis of tuberculous
      pleuritis. DESIGN: We applied polymerase chain reaction (PCR) to detect DNA
      (IS6110) specific for Mycobacterium tuberculosis complex in pleural biopsy
      specimens. RESULTS: Of 28 patients with pleural disease, 11 were diagnosed by
      microbiology (smear/culture of sputum or pleural fluid) with tuberculous
      pleuritis, eight were diagnosed with tuberculous pleuritis by histology (of
      pleural biopsies) and/or clinical presentation, and nine were diagnosed with
      carcinomatous pleuritis. Seventeen of the patients' pleural biopsies were PCR
      positive. Based on microbiological results, the sensitivity of the PCR assay was
      100% (11/11). On the other hand, based on the results of the histological and
      clinical data, sensitivity and specificity of the PCR results were 89% (17/19)
      and 100% (9/9), respectively. CONCLUSION: PCR of pleural biopsy specimens can be
      a useful method when employed in combination with microbiological and
      histological examinations of pleural biopsy for rapid diagnosis of tuberculous
      pleuritis.

PMID- 9559409
TI  - The effect of ranitidine on the tuberculin skin test.

PMID- 9559410
TI  - Missed opportunities for prevention of tuberculosis.

PMID- 9559411
TI  - Comparison of coronary hemodynamics during infusions of dobutamine and adenosine
      in patients with angina pectoris.
AB  - Pharmacologic stress tests are used to evaluate the significance of coronary
      arterial stenosis, and adenosine and dobutamine are often used for this purpose.
      The aim of this study was to examine coronary hemodynamics in 16 patients with
      stable exertional angina who had organic stenosis (> 90%) in the left anterior
      descending coronary arteries and in 13 control subjects at baseline and during
      separate intravenous infusions of dobutamine (20 micrograms/kg per min
      [corrected]) and adenosine (140 micrograms/kg per min [corrected]). Measurements
      of great cardiac vein blood flow and lactate and oxygen contents in the blood
      from the aortic root and great cardiac vein were analyzed in patients with
      ischemic signs of myocardial ischemia (ST-segment depression in the precordial
      ECG leads and/or myocardial lactate production) during the infusions (in 11
      patients during adenosine infusion and in 12 patients during dobutamine infusion)
      and in control subjects. Myocardial oxygen consumption during adenosine infusion
      did not change compared with the baseline in both groups, whereas it increased
      during dobutamine infusion in both groups (p < 0.01 compared with the baseline in
      each case). However, great cardiac vein blood flow was significantly increased
      compared with the baseline during both infusions in both groups (p < 0.01
      compared with baseline in each case), and the oxygen contents of great cardiac
      vein blood, which contains effluent from the ischemic region, showed no decrease
      but increased significantly during both infusions in the patients in comparison
      with control subjects. Although the global oxygen supply was excessive,
      myocardial ischemia occurred during dobutamine and adenosine infusions in the
      patients. As myocardial oxygen consumption remained unchanged during adenosine
      infusion, regional myocardial flow reduction, possibly as a result of flow
      maldistribution, may contribute, at least partly, to adenosine-induced myocardial
      ischemia. An increase in myocardial oxygen consumption may be the principal cause
      of myocardial ischemia during dobutamine infusion, but an inappropriate flow
      increase in normal myocardium may occur during dobutamine-induced ischemia.

PMID- 9559412
TI  - Relationship between serum cholesterol and the risk of acute myocardial
      infarction in a screened cohort in Okinawa, Japan.
AB  - Coronary heart disease (CHD) is rare in Japanese subjects and serum cholesterol
      levels are low. However, no data have been published relating the effect of serum
      cholesterol levels to the incidence of acute myocardial infarction (AMI) in
      Japan. Data from a large community-based mass screening registry are available
      for the geographically isolated island of Okinawa, Japan (1980 census, 1.11
      million). A total of 38,053 participants (17,859 men and 20,194 women) whose
      serum cholesterol levels were determined in the 1983 mass screening were examined
      to determine whether they had experienced AMI. Every case of AMI that occurred
      during a 3-year period (1 April 1988 to March 1991) throughout Okinawa was
      recorded in a separate registry. The total number of cases of AMI was 1,021 (674
      men and 347 women). Of these, 65 patients (41 men and 24 women) were identified
      by name, sex, birth date, and zip code in the mass screening registry. The
      cumulative incidence of AMI increased with the serum level of cholesterol: 42.1
      (serum cholesterol < or = 167 mg/dl), 133.5 (serum cholesterol 168-191 mg/dl),
      188.9 (serum cholesterol 192-217 mg/dl), and 323.0 (serum cholesterol > or = 218
      mg/dl) per 100,000 screened subjects. Multiple logistic analysis was conducted to
      examine the effect of serum cholesterol on the risk of AMI with adjustment for
      other variables such as sex, age, systolic and diastolic blood pressure, and
      proteinuria. The adjusted odds ratio (95% confidence interval) of the observed
      serum levels of cholesterol was 1.66 (1.29-2.15) with a reference serum
      cholesterol level of < or = 167 mg/dl. The risk of AMI increased in proportion to
      the serum level of cholesterol. Serum cholesterol is an independent predictor of
      AMI in Okinawa, Japan.

PMID- 9559413
TI  - Impaired atrial contraction in patients with atrial flutter and gradual recovery
      after cardioversion.
AB  - The risk of thromboembolism after cardioversion of atrial flutter is
      controversial. The present study provides evidence for blood stasis in the atria
      of patients with atrial flutter and for gradual recovery of atrial contraction
      after cardioversion, which justifies prophylactic treatment at cardioversion, as
      for atrial fibrillation. We examined atrial thrombi and peak flow velocity in the
      left atrial appendage as an index of blood stasis in 5 consecutive patients with
      atrial flutter. Transesophageal echocardiography revealed a thrombus in 1
      patient, and peak flow velocity in the left atrial appendage was inversely
      correlated with left atrial dimension (r = -0.90, p < 0.05). After restoration of
      sinus rhythm, transmitral flow velocity in late diastole was also examined to
      evaluate the recovery of atrial contraction. The recovery of transmitral flow
      velocity the next day and 1 week after cardioversion was correlated with flow
      velocity in the left atrial appendage before cardioversion (r = 0.89, p < 0.05; r
      = 0.97, p < 0.01, respectively). These findings suggest that some patients with
      atrial flutter have impaired atrial contraction and that prolonged impairment
      after cardioversion is also possible. Atrial enlargement and low flow velocity in
      the atrial appendage were predictive factors for such patients.

PMID- 9559414
TI  - Relationship between calcium channel antagonists and nocturnal hypotension and
      autonomic imbalance in patients with a previous myocardial infarction.
AB  - The present study was conducted to evaluate the effect of calcium channel
      antagonists on diurnal changes in blood pressure and on autonomic function in 71
      patients who were receiving a calcium channel antagonist because they had
      previously suffered a myocardial infarction. Ambulatory blood pressures and
      Holter ECGs were recorded simultaneously for 24 h. Autonomic function was
      assessed by heart rate variability. Nocturnal systolic pressure was > or = 90
      mmHg in 63 patients (group I) and < 90 mmHg in 8 patients (group II). Significant
      day to night changes in high-frequency power (from 4.3 +/- 1.2 to 4.5 +/- 1.0/m2)
      as well as in the ratio of low-frequency power to high-frequency power (from 1.3
      +/- 0.1 to 1.1 +/- 0.2) were observed in group I. whereas such changes were
      blunted in group II. When the calcium antagonist was discontinued or the dose was
      reduced in group II, the autonomic imbalance improved along with elevation of
      nocturnal systolic blood pressure. Thus, nocturnal blood pressure should be
      monitored when such drugs are administered for the treatment of ischemic heart
      disease to a patient with a previous myocardial infarction. If nocturnal
      hypotension occurs, the dose should be reduced or the drug should be
      discontinued.

PMID- 9559415
TI  - Hormonal and cardiorenal responses to acute saline loading in mild congestive
      heart failure--the effect of angiotensin converting enzyme inhibition.
AB  - We investigated cardiorenal responses to acute saline loading in patients with
      mild congestive heart failure (CHF) with and without angiotensin-converting
      enzyme (ACE) inhibition. Saline loading (infusion of 250 ml of normal saline) was
      performed on 10 patients with mild CHF and 10 control subjects. Although saline
      loading reduced plasma renin activity and plasma angiotensin II to a similar
      extent in both groups, it increased cardiac output, renal blood flow, and the
      ratio of renal blood flow to cardiac output in the mild CHF group but not in the
      control group. After saline loading, urinary sodium excretion was higher in the
      control than in the mild CHF group. In the mild CHF group, saline loading was
      performed again after an ACE inhibitor (delapril) had been administered for 5
      days. Although delapril increased cardiac output and renal blood flow under basal
      conditions, saline loading did not affect these variables. Delapril improved
      urinary sodium excretion after saline loading. Thus, the renin-angiotensin
      aldosterone axis may contribute to cardiorenal hemodynamics and renal sodium
      handling in patients with mild CHF. This effect may attenuate the natriuretic
      response to acute saline loading, and administration of an ACE inhibitor improves
      this attenuation.

PMID- 9559416
TI  - Altered calcium handling in compensated hypertrophied rat cardiomyocytes induced
      by pressure overload.
AB  - To investigate Ca2+ handling in compensated hypertrophied cardiomyocytes, we
      measured Ca2+ transients and contraction of hypertrophied rat left ventricular
      myocytes induced by aortic constriction (AC). The fluorescence ratio (I405/I480)
      after indo-1/AM loading and circumferential length were simultaneously measured
      in isolated myocytes. The amplitude of Ca2+ transients (Ca-Amp) was higher in
      rats with AC than in sham-operated rats (Sham) (0.25 +/- 0.08 vs 0.17 +/- 0.05).
      There was a positive correlation between Ca-Amp and fractional shortening (FS) in
      both AC and Sham rats, whereas the ratio of FS/Ca-Amp was smaller in AC rats.
      These observations suggest that compensated hypertrophied cardiomyocytes exhibit
      an adaptive increase in Ca-Amp, associated with reduced myofilament
      responsiveness to an increase in Ca2+. Isoproterenol and forskolin increased Ca
      Amp and FS, and decreased time to 50% decline of Ca2+ transients. Although
      myocytes from AC rats exhibited reduced responsiveness to isoproterenol,
      responses to forskolin did not differ between the 2 groups. The reduced beta
      adrenergic response in Ca2+ handling was probably due to altered beta
      adrenoceptor numbers, G-protein function and/or their coupling process.

PMID- 9559417
TI  - Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol
      induced left ventricular hypertrophy.
AB  - We examined the effect of a calcium antagonist, manidipine hydrochloride, on
      cardiac hypertrophy and the expression of the atrial natriuretic peptide (ANP),
      transforming growth factor beta 1 (TGF-beta 1), and extracellular matrix protein
      genes in rats with isoproterenol-induced cardiac hypertrophy. Rats were
      continuously infused with saline or isoproterenol (0.5 mg/kg per day) for 7 days
      using an osmotic minipump. Treatment with manidipine hydrochloride (once a day at
      3 mg/kg) began 1 day before minipump implantation and continued until the end of
      the experiments (each group; n = 6). After treatment, left ventricular weight was
      measured and mRNA was extracted and analyzed by Northern blot hybridization.
      Isoproterenol increased left ventricular weight (2.40 +/- 0.04 g/kg; p < 0.01)
      without increasing blood pressure. ANP, collagen type I and type III, and
      fibronectin mRNAs were increased 1.5-(p < 0.01), 1.9- (p < 0.01), 2.7- (p <
      0.01), and 3.2-fold (p < 0.01), respectively, by isoproterenol infusion. However,
      TGF-beta 1, collagen type IV, and laminin B1 and B2 mRNA levels were unchanged by
      isoproterenol. Manidipine hydrochloride prevented isoproterenol-induced left
      ventricular hypertrophy (2.26 +/- 0.02 g/kg; p < 0.01) and expression of mRNA of
      ANP (0.9-fold of the control value; p < 0.01), collagen types I (1.1-fold; p <
      0.01) and type III (1.6-fold; p < 0.01), and fibronectin (1.1-fold; p < 0.01).
      Thus, manidipine hydrochloride prevented cardiac hypertrophy and changes in the
      expression of genes for ANP and interstitial components of extracellular matrix
      induced by isoproterenol.

PMID- 9559418
TI  - Limitations of angiotensin-converting enzyme inhibitor in restenosis of a deep
      arterial injury model.
AB  - Cilazapril (CLZ) has been reported to reduce intimal hyperplasia in a rat carotid
      model of restenosis. The purpose of this study was to determine whether CLZ
      inhibits restenosis after deep arterial injury in lathyritic rats. The lathyritic
      rat was used as a model of deep arterial injury; in this model the internal
      elastic lamina is easily broken by balloon injury because of the fragility of the
      connective tissue. Deep arterial injury is defined as rupture of the internal
      elastic lamina with damage to both the intima and the media. The rats were
      divided into 4 groups (n = 40): mild injury (intimal damage with intact internal
      elastic lamina), mild injury +CLZ, deep injury, and deep injury +CLZ. In the CLZ
      treated groups, the drug was administered orally (10 mg/day) from 7 days before
      balloon injury until the time of sacrifice 21 days after balloon injury. The
      intimal hyperplasia was determined histologically using a computerized
      morphometry program. At sacrifice, blood pressure was lower in the CLZ-treated
      groups than in the untreated (control) rats (p < 0.05). In the mild injury model,
      CLZ decreased intimal hyperplasia markedly. In contrast, CLZ failed to reduce
      intimal hyperplasia in the rats with deep injury. CLZ markedly decreased
      neointimal hyperplasia in mild injury. In contrast, CLZ failed to reduce intimal
      area in deep injury. The type of arterial injury seems to determine the
      effectiveness of CLZ.

PMID- 9559419
TI  - A case of pulmonary embolism caused by paroxysmal nocturnal hemoglobinuria.
AB  - A patient with pulmonary embolism caused by paroxysmal nocturnal hemoglobinuria
      (PNH) is described. PNH sometimes causes venous thrombosis in the extremities,
      hepatic vein, or cerebral vein, but pulmonary embolism rarely occurs.

PMID- 9559420
TI  - Aortic root replacement for Takayasu arteritis associated with ulcerative colitis
      and ankylosing spondylitis--report of a case.
AB  - A 26-year-old man was admitted for treatment of congestive heart failure
      resulting from aortic regurgitation. The patient had been on medical treatment
      for ulcerative colitis (UC) since he was 14 years old and for ankylosing
      spondylitis (AS) since he was 20 years old. On admission, gradients of blood
      pressure among the extremities were observed. Echocardiography revealed marked
      dilation of the left ventricle (LV), hypokinetic wall motion of the LV, slightly
      prolapsed aortic cusps with annular dilatation, and severe aortic regurgitation.
      Computed tomographic scans demonstrated an aneurysmal dilation of the ascending
      aorta and thickening of the descending and abdominal aortic wall. Digital
      subtraction angiography demonstrated an aneurysmal dilation of the ascending
      aorta; however, there was no clear evidence of steno-occlusive lesions in the
      brachiocephalic vessels. Blood studies showed positive inflammatory signs and
      negative rheumatoid factor. HLA typing showed A2, 24(9), B27, 67, Cw1, 7, and
      DR1, 2. Based on these data, the diagnosis of Takayasu arteritis associated with
      UC and AS was made. Aortic root replacement was performed. Steroid therapy was
      restarted immediately after surgery. Histologic studies of the aortic wall showed
      findings compatible with Takayasu arteritis. The combination of these rare
      diseases suggests that they have a common pathophysiologic background.

PMID- 9559421
TI  - Surgical treatment of discrete subaortic stenosis in an adult.
AB  - We report on an adult patient with discrete-type subaortic stenosis. A 48-year
      old man who had progressed asymptomatically since childhood despite heart murmur
      was transferred to our hospital. The patient was diagnosed as having severe
      aortic stenosis with a pressure gradient of 100 mmHg across the aortic valve,
      associated with a grade II aortic regurgitation. A conventional aortic valve
      replacement was scheduled. During surgery, the aortic valve was found to be
      tricuspid but incompetent as a result of shrinking and thickening of the left
      coronary cusp. A circumferential fibromuscular ridge was observed under the
      cusps, which corresponded to Kelly's type II discrete subaortic stenosis. Because
      of the small subaortic area and deformity of the cusp, we performed aortic valve
      replacement after excision of all cusps and the fibromuscular ridge. Early
      corrective surgery is recommended for discrete subaortic stenosis to prevention
      regurgitation progression.

PMID- 9559422
TI  - A case of severe verapamil overdose.
AB  - We report here on a 73-year-old woman who ingested 3.6 g (40 mg x 90 tablets) of
      verapamil in a suicide attempt. On arrival, the patient was awake and well
      oriented. Two and a half hours after ingestion, she lost consciousness, as her
      heart rate and blood pressure began to decrease. Cardiac monitoring showed
      atrioventricular dissociation. Although she suffered from extreme hypotension, an
      echocardiogram revealed that the wall motion of the heart was almost normal, and
      cardiac output measured with a Swan-Ganz catheter was well preserved. The plasma
      verapamil concentration in this patient was 1499 ng/ml 4 h after ingestion.
      Hyperglycemia and hypokalemia, laboratory data revealed, continued for 18 h after
      admission. The patient was successfully resuscitated with intravenous saline,
      dopamine, and norepinephrine. Besides reporting on this case, we also report on a
      treatment for severe verapamil overdose.

PMID- 9559423
TI  - Ischemic and non-ischemic myocyte damage and antimyosin monoclonal imaging.
AB  - Antimyosin monoclonal antibody is a specific marker of impaired sarcolemmal
      integrity resulting not only from ischemia but also from non-ischemic myocardial
      injury, such as infection, inflammatory, or immunologic reactions, and alcohol or
      drug intoxication. In addition, antimyosin accumulation has been demonstrated in
      some forms of cardiomyopathy with unknown as well as known etiologies. Antimyosin
      positivity appears to indicate precisely the extent of myocardial necrosis and to
      reflect cardiac dysfunction in an acute stage of active myocardial damage caused
      by ischemia and inflammation. However, the correlation is not necessarily good in
      the chronic stages of the disease or in idiopathic cardiomyopathic hearts; in
      other words, cardiac antimyosin uptake can be detected even in myocardial tissue
      with a normal histologic appearance independent of the presence of inflammatory
      responses, myocyte necrosis, or functional or morphologic deterioration. Thus,
      antimyosin is useful not only for detecting and quantifying acute myocardial
      necrosis but also for specifically identifying ongoing or latently progressing
      myocardial degeneration and sarcolemmal disruption, which will certainly lead to
      myocardial necrosis. These characteristics may contribute to the early detection
      of myocardial damage and lead to the investigation of pathophysiologic
      mechanisms. Further progress in immunologic and radiolabeling techniques is
      necessary for better specificity and less antigenicity against humans in
      antimyosin monoclonal antibody imaging.

PMID- 9559424
TI  - Comparative study of dobutamine stress electron-beam computed tomography and
      exercise thallium scintigraphy in the diagnosis of patients with suspected
      coronary artery disease.
AB  - To evaluate the diagnostic value of dobutamine stress electron-beam computed
      tomography (EBCT) as compared with exercise stress thallium-201 single-photon
      emission computed tomography (201T1-SPECT) for the detection of myocardial
      ischemia, 10 patients with proven or suspected coronary artery disease underwent
      both tests. Nine of the 10 patients also underwent coronary angiography. EBCT
      images were analyzed objectively to evaluate systolic wall thickening and
      analyzed segmentally to determine the distribution of the coronary arteries.
      Dobutamine stress EBCT revealed the presence of ischemia in 59 segments, whereas
      exercise stress 201T1-SPECT revealed ischemia in 51 segments (agreement = 73%).
      The advantage of dobutamine stress EBCT was demonstrated in the
      inferior/posterior segments as compared with the results of exercise stress 201T1
      SPECT. The overall sensitivity for detecting ischemic regions supplied by
      coronary arteries with significant stenosis (diameter stenosis > 50%) was 83% for
      dobutamine stress EBCT and 79% for exercise stress 201T1-SPECT (p = NS), with
      specificities of 75% and 82% (p = NS). Thus, dobutamine stress EBCT presents a
      reasonable alternative to exercise stress 201T1-SPECT for the objective
      assessment of patients with suspected coronary artery disease.

PMID- 9559425
TI  - Characterization of left ventricular opacification using sonicated serum albumin
      in patients with dilated cardiomyopathy and myocardial infarction.
AB  - To elucidate whether the mode of left ventricular opacification using sonicated
      serum albumin (SSA) is dependent upon the severity of left ventricular
      dysfunction, SSA was administered intravenously to 26 patients with dilated
      cardiomyopathy, 24 patients with anteroseptal myocardial infarction, and 9 normal
      control subjects. The left ventricular inflow pattern in echocardiograms on the
      apical 4-chamber view was classified into 2 types: straight or whirling. The
      ratio of left ventricular opacified area to left ventricular end-diastolic area,
      called the percent left ventricular effective fraction (%LVEF), was also
      calculated. The inflow pattern was straight in all normal control subjects and 9
      myocardial infarction patients, whereas 15 myocardial infarction and all dilated
      cardiomyopathy patients showed the whirling pattern. Percent LVEF was
      significantly smaller in patients with dilated cardiomyopathy (45 +/- 22%, p <
      0.0001) and myocardial infarction (65 +/- 14%, p < 0.001) than in normal control
      subjects (84 +/- 7%). The area that was not opacified was observed only in the
      infarcted area in cases of myocardial infarction, and over wide regions in cases
      of dilated cardiomyopathy. In addition, there were significant correlations
      between %LVEF and ejection fraction or peak filling rate. These findings indicate
      that contrast echocardiography using SSA can reflect sensitively the severity of
      left ventricular dysfunctions and detect the regions involved in patients with
      dilated cardiomyopathy and myocardial infarction.

PMID- 9559426
TI  - Assessment of the Bjork-Shiley prosthetic valve orifice area in the aortic
      position.
AB  - The actual orifice area of a valve is still considered to be a valuable index for
      assessing prosthetic valve function. Valve orifice area as calculated by Gorlin's
      formula is, however, not constant but changes in proportion to the transvalvular
      flow rate. The purpose of the present study was to examine the relationship
      between orifice area and flow rate across the Bjork-Shiley prosthetic valve as
      calculated by Gorlin's formula, and to modify the formula in a series of patients
      with the Bjork-Shiley prosthetic valve in the aortic position. Fifty-six patients
      who had received aortic valve replacement with a Bjork-Shiley prosthetic valve
      underwent cardiac catheterization. Prosthetic valve orifice area was calculated
      by Gorlin's formula and then plotted against flow rate across the valve with
      respect to valve size. The relationship between orifice area and flow was linear.
      The discharge coefficient of Gorlin's formula was plotted against flow rate, and
      a linear correlation was obtained. By substituting Gorlin's formula for an
      empiric coefficient into the function for transvalvular flow rate, a modified
      formula that can predict the actual orifice area of the prosthetic valve is
      obtained.

PMID- 9559427
TI  - Outcome of medically treated Stanford type B aortic dissection.
AB  - Optimal treatment for patients with uncomplicated type B dissection remains a
      matter of debate. From January, 1987, through June, 1996, 43 patients with acute
      type B dissection were treated exclusively by medical therapy according to our
      management guidelines. After discharge, aortography and enhanced computed
      tomography were performed every 6 months to evaluate the diameter of the
      dissected aorta. All 43 patients survived the acute phase and were discharged
      alive from the hospital. There was no death related to aortic dissection. Three
      patients underwent surgical treatment in the chronic phase because of aortic
      enlargement. Aortic enlargement in 3 additional patients was managed medically.
      The values for freedom from aortic enlargement for 43 patients at 1, 3, and 5
      years were 100%, 91%, and 86%, respectively. The long-term survival rates of
      patients treated medically and discharged from the hospital are acceptable.

PMID- 9559428
TI  - Deep hypothermic intermittent circulatory arrest--an adjunct technique for
      operations on aneurysms involving the aortic arch.
AB  - Aneurysms involving the aortic arch were repaired in 12 patients using a
      technique known as deep hypothermic intermittent circulatory arrest (DHICA). This
      technique consists of repeated cycles of 20 min of circulatory arrest and 10 min
      of cerebral and systemic reperfusion. Aneurysms were of the following types: 2
      true atherosclerotic aneurysm, 8 aortic dissections, and 2 traumatic aneurysm.
      There were 2 operative deaths caused by coagulopathy as a result of hepatic
      failure and difficulty with left ventricular venting. The frequency of
      circulatory arrest ranged from 2 to 5 cycles, and total circulatory arrest ranged
      from 20 to 71 min (mean 43.6 min). The lowest tympanic temperature ranged from
      17.7 to 19.2 degrees C. No permanent cerebral complications occurred in 10
      patients. We believe that this adjunct technique offers excellent results in the
      surgical treatment of aneurysms involving the aortic arch.

PMID- 9559429
TI  - Angiographic study of mutant tissue-type plasminogen activator versus urokinase
      for acute myocardial infarction.
AB  - The effects and problems of intravenous thrombolytic therapy with a bolus
      injection of mutant tissue plasminogen activator (t-PA) were investigated in 34
      patients with first acute myocardial infarction (AMI). In contrast, 114 patients
      were selected from 1,003 patients with AMI for treatment using intravenous
      infusion urokinase (UK). Angiography of these 148 patients revealed a complete
      occlusion of infarct-related artery with no clear contraindications to the study
      treatment. With the exception of thrombolysis in myocardial infarction (TIMI-3)
      recanalization 60 min after a bolus injection of mutant t-PA, the patients were
      given intracoronary UK in addition to mutant t-PA. The study comparisons were
      assessed using the following criteria: (1) 60-min assessment of recanalization
      rates, mutant t-PA vs UK; (2) time interval from initiation of thrombolysis to
      recanalization, mutant t-PA vs UK; (3) angiographic reocclusion rates within 1
      month, mutant t-PA alone vs UK vs mutant t-PA plus UK; and (4) intracerebral
      hemorrhage rates, mutant t-PA alone vs UK vs mutant t-PA plus UK. There were no
      significant differences in the recanalization rates between mutant t-PA and UK,
      but there was a significant reduction in the time to recanalization with mutant t
      PA (31.8 +/- 12.7 min) compared with UK (56.5 +/- 6.3 min). There was a
      significant difference in the reocclusion rates among the 3 treatment groups (20%
      mutant t-PA alone vs 4% UK vs 0% mutant t-PA plus UK). On the other hand, no
      significant differences in intracerebral hemorrhage rates among the 3 treatments
      were observed. In conclusion, thrombolytic therapy with a bolus injection of
      mutant t-PA achieved more rapid recanalization, but treatment with mutant t-PA
      led to a high rate of reocclusion.

PMID- 9559430
TI  - Evaluation of an automatic intraluminal edge detection technique for
      intravascular ultrasound images.
AB  - Intravascular ultrasound (IVUS) imaging enables detailed analysis and precise
      measurements of vascular cross-sections. However, to achieve a reduction in the
      existing level of observer variability requires the development of quantitative
      IVUS. We have developed a fully automatic intraluminal edge detection technique,
      based on adaptive active contour models and called ADDER (adaptive damping
      dependent on echographic regions) that allows the quantitation of the
      intraluminal cross-sectional area (ICSA). Using a 30-MHz mechanically rotated
      transducer mounted at the tip of a 3.5-F catheter, 58 normal and pathologic
      arterial segments (from coronary, renal, splenic, iliac, and carotid arteries)
      were imaged in vitro. These images were analyzed by 2 experts, E1 and E2, who
      manually traced the intraluminal contour twice for each image, as well as with
      ADDER. Intra-observer variabilities for ICSAs were found to be excellent (-1.454
      +/- 3.51% for E1, 0.96 +/- 5.4% for E2). The inter-observer variability was 2.1
      +/- 4.3%. The success factor for ADDER was 89%. Its intra-observer variability
      was null, as the method always finds a unique contour. The correlation between
      the automatically detected ICSA and the manual ICSA was: r = 0.99 (y = 1.03x +
      0.89 mm2). Morphometric variations between manually and automatically traced
      contours, analyzed by the centerline method, were 100 +/- 140 mm on average. In
      conclusion, the ADDER automatic contour detection applied to IVUS images is
      robust and characterized by small systematic and random errors; therefore,
      quantitative IVUS is a useful tool in clinical research trials.

PMID- 9559431
TI  - Comparison of the effects of enoximone and isoproterenol on protamine
      cardiotoxicity in anesthetized dogs.
AB  - In this study we investigated the effects of isoproterenol and enoximone on
      protamine cardiotoxicity because administration of protamine for heparin reversal
      during open heart surgery depresses left ventricular function. Eighteen mongrel
      dogs were entered into this study. After induction of general anesthesia and a
      stabilization period, a thermodilution catheter was inserted via the jugular
      vein. Another 2 catheters were inserted into the left ventricle and femoral
      artery. Heparin and protamine were used in all animals. Heparin dosage was 300
      U/kg, and protamine dosage was 4.5 mg/kg. The animals were divided into 3 groups.
      Six animals received enoximone (5 micrograms/kg per min), 6 animals received
      isoproterenol (0.05 microgram/kg per min), and 6 animals received no inotropic
      agent. Measurements were performed before treatment, 5 min after protamine
      administration, and at 15-min intervals for 1 h. Cardiac output (CO), mean
      arterial pressure, pulmonary capillary wedge pressure, first derivative of left
      ventricular pressure (1 +/-) left ventricular systolic pressure, and heart rate
      were measured. CO was 1582 +/- 34 ml/min in the isoproterenol group (I + P), 1684
      +/- 61 ml/min in the enoximone group (E + P), and 1471 +/- 37 ml/min in the
      protamine group (P) (p < 0.05 E + P vs I + P and P) 60 min after protamine
      administration. The first derivative of left ventricular pressure (dP/dt) was
      1995 +/- 61 mmHg/sec in the I + P group, 2320 +/- 85 mmHg/sec in the E + P group,
      and 1816 +/- 48 mmHg/sec in the P group (p < 0.05 E + P vs I + P and P). In our
      experimental study, the isoproterenol and protamine combination did not increase
      hemodynamic activity. However, isoproterenol alone significantly increased
      hemodynamic activity as determined by dP/dt values. Protamine administration
      impairs the effects of beta agonists on the myocardium. In the protamine group,
      CO and pressure-dependent values were significantly reduced. Isoproterenol
      administration did not reverse this deterioration because of the loss of the beta
      receptor activity. Inotropic agents acting through the beta-adrenergic system
      have partial effects on myocardium. Enoximone, a phosphodiesterase inhibitor,
      reverses deterioration of cardiac function after protamine administration because
      it increases myocardial function via the phosphodiesterase system.

PMID- 9559432
TI  - Hypertrophic cardiomyopathy with apical left ventricular aneurysm.
AB  - We report a case of hypertrophic cardiomyopathy (HCM) with apical left
      ventricular aneurysm, which is difficult to review because cases are so rare. A
      54-year-old Japanese man was first found to have an electrocardiographic
      abnormality (T-wave inversion at rest) 19 years ago, and non-obstructive apical
      HCM without identifiable cause was diagnosed by echocardiography, left
      ventriculography, and clinical findings. After 19 years, he was admitted because
      of repeated episodes of palpitation and chest oppression at rest. Widespread left
      ventricular hypertrophy from the anteroseptal wall to the apex with an apical
      left ventricular aneurysm was detected by echocardiography, left
      ventriculography, and cardiac magnetic resonance imaging. Histologic examination
      of the hypertrophic apical myocardium surrounding the aneurysm showed that the
      myocardial tissue had been extensively replaced by fibrous tissue containing
      hypertrophic myocardial fibers, and uptakes of [123I]-metaiodobenzyl guanidine
      (MIBG) and [123I-] beta-methyliodophenyl pentadecanoic acid (BMIPP) in single
      photon emission photography images were reduced despite high myocardial
      perfusion. On the other hand, histologic examination of the hypertrophic anterior
      wall revealed myocardial hypertrophy with disorganization; myocardial perfusion
      and the uptakes of MIBG and BMIPP were preserved. Abnormalities of myocardial
      fatty acid metabolism and sympathetic neuron activity with preserved perfusion
      flow and histologic changes such as fibrosis in the apical wall are indicative of
      apical myocardial injury or ischemia (infarction) without coronary artery
      stenosis; apical aneurysm may have occurred in severe apical HCM with cavity
      obliteration up to the midventricular level.

PMID- 9559433
TI  - Eosinophilic myocarditis associated with toxicodermia caused by phenobarbital.
AB  - We report on a 37-year-old man with congestive heart failure caused by
      eosinophilic myocarditis associated with toxicodermia. He developed many annular
      skin eruptions and peripheral eosinophilia due to reactions against
      phenobarbital. Right ventricular endomyocardial biopsy revealed extensive
      infiltration of eosinophils in the myocardium. A drug lymphocyte-stimulating test
      (DLST) for phenobarbital was positive. His symptoms, cardiomegaly, and cardiac
      function were improved by discontinuing phenobarbital followed by oral
      administration of prednisolone. We conclude that this eosinophilic myocarditis
      must have been induced by an allergic reaction to phenobarbital and that long
      term eosinophilia contributed to the myocardial injury.

PMID- 9559434
TI  - Asymptomatic moyamoya disease associated with coronary and renal artery stenoses-
      a case report.
AB  - Moyamoya disease is an occlusive intracranial arteriopathy with abnormal cerebral
      vascular collateral networks. Although this disease is known to be associated
      with stenosis of extracranial arteries, such as the renal artery, a case
      associated with stenoses of the coronary and renal arteries has not been
      reported. We described here a 23-year-old man who had effort angina, renovascular
      hypertension, and asymptomatic moyamoya disease. Arterioangiography revealed
      bilateral occlusion of the intracranial carotid arteries and stenoses in the left
      coronary artery and the left renal artery.

PMID- 9559435
TI  - Purulent pericarditis with tamponade caused by Salmonella enteritidis.
AB  - The incidence of purulent pericarditis has declined. However, mortality remains
      high. We describe a case of purulent pericarditis with tamponade caused by
      Salmonella enteritidis, and emphasize the importance of early recognition, prompt
      institution of appropriate antibiotic therapy, and early surgical drainage for
      survival.

PMID- 9559436
TI  - Ischemic change on electrocardiogram induced by hypoglycemia in a diabetic
      patient.
AB  - A 34-year-old female patient who presented to our hospital had been treated with
      insulin for diabetes since she was 25 year old. For the previous year she had
      experienced chest pain on exertion and during hypoglycemia. During both chest
      pain and exercise tests, ST depression and flattening of the T wave were
      recognized in leads II, III, aVF, and V2-V6 on the electrocardiogram, and thus
      ischemic heart disease was suspected. Cardiac catheterization was performed, but
      no organic stenosis or spasms were found. Hypoglycemia (41 mg/dl) was induced by
      intravenous injection of rapid insulin (total 18 U, 0.4 U/kg). However, no
      coronary change was seen, although she felt chest pain and the same ischemic
      electrocardiographic changes occurred. We hypothesized the causes of the ischemic
      change to be both the effects of insulin on the cardiovascular system and the
      physiologic stress induced by the existence of microvascular abnormality. Special
      care should therefore be taken with diabetic patients being treated with insulin
      or hypoglycemic agents.

PMID- 9559437
TI  - Transient left bundle branch block induced by left-sided cardiac catheterization
      in patients without pre-existing conduction abnormalities.
AB  - A traumatic left bundle branch block (LBBB) is uncommon in a patient with intact
      atrioventricular conduction. Three of our patients developed LBBB during a left
      sided catheterization. Two patients suffered from angina pectoris and the other
      had an abdominal aneurysm. Two of them had a history of hypertension. None of the
      patients had ever shown any conduction abnormalities before the catheterization.
      The electrocardiogram just before the examination was normal in all 3 patients.
      LBBB was observed when a catheter was introduced into the left ventricle, and
      lasted 2--4 min without significant change in heart rates. Examination revealed
      no significant stenosis proximal to the first septal perforator and normal left
      ventricular contraction in all patients. One patient developed permanent LBBB 14
      months later. Catheter-induced LBBB may occur easily with certain anatomical
      characteristics of the left bundle branch or the distal His bundle, with or
      without some concealed damage to the conduction system. It is important to keep
      this complication in mind and to pay adequate attention to patients'
      electrocardiograms as well as their angiographical findings, especially in those
      with pre-existing right bundle branch block.

PMID- 9559438
TI  - A case of dobutamine-induced coronary arterial spasm with ST-segment elevation.
AB  - A 55-year-old Japanese woman demonstrated ST-segment elevation in leads I, aVL,
      and V3-V6 with chest pain both in an ergometer exercise test and on dobutamine
      stress echocardiography. Although the baseline coronary arteriogram revealed no
      organic stenosis, total occlusion of the distal portion of the posterolateral
      branch of the left circumflex artery was observed during dobutamine infusion with
      ST-segment elevation and chest pain. This is a rare case of documented dobutamine
      induced coronary arterial spasm.

PMID- 9559439
TI  - Effects of thymosin alpha-1 on erythrocyte lipid levels and erythrocyte membrane
      (Na(+)-K+)-ATPase activity in experimental hypercholesterolemia.
AB  - Thymosin alpha-1 is an active polypeptide isolated from thymus. This polypeptide
      is widely used in the diagnosis and treatment of many diseases, especially immune
      diseases. In this present study, we examined the effects of thymosin alpha-1 on
      plasma and erythrocyte lipid levels and the changes in erythrocyte membrane (Na+,
      K+)ATPase activity in hypercholesterolemic rabbits. The erythrocyte lipid levels
      decreased, whereas the erythrocyte membrane (Na+, K+)ATPase activity increased
      significantly in these rabbits after thymosin alpha-1 injection. These findings
      suggest that thymosin alpha-1 is effective on both the lipid level and
      erythrocyte membrane (Na+, K+)ATPase activity.

PMID- 9559440
TI  - Evaluation of culture, histological examination, serology and the rapid urease
      test for diagnosis of Helicobacter pylori in patients with dyspepsia in
      Bangladesh.
AB  - Helicobacter pylori, a gram-negative, microaerophilic bacterium, has been
      established to have a causal association with chronic gastritis, peptic ulcer,
      gastric adenocarcinoma, and low-grade lymphoma. The present study was undertaken
      to evaluate the efficacy of culture, histological examination, the rapid urease
      test, and serology for the diagnosis of H. pylori infection. A total of 45
      consecutive subjects with various upper gastrointestinal symptoms were included
      in this study. The rates of diagnosis of H. pylori infection were 51.1%, 55.6%,
      82.2%, and 93.3%, by culture, rapid urease test (RUT), histological examination,
      and serology, respectively. The sensitivity, specificity, and positive and
      negative predictive values were 95.5%, 82.6%, 84.0%, and 95.0%, respectively for
      RUT; 95.5%, 30.4%, 56.8%, and 87.5% for histological examination; 100%, 13.6%,
      54.8% and 100% for serology.

PMID- 9559441
TI  - Discrimination of Listeria monocytogenes strains of serotype 4b by restriction
      enzyme analysis of chromosomal DNA.
AB  - Epidemiologically related cheese and environmental strains and epidemiologically
      unrelated strains of Listeria monocytogenes serotype 4b were examined by
      restriction enzyme analysis of chromosomal DNA with a total of 10 restriction
      enzymes. The DNA fingerprint patterns generated from each restriction enzyme
      digest of total DNA of all strains were classified. The restriction enzyme
      patterns of seven strains recovered from cheese and environmental samples in the
      same plant were identical to each other, but differed from those of seven
      epidemiologically unrelated strains. Two, originating from sporadic human
      patients, of eight epidemiologically unrelated strains exhibited the identical
      restriction enzyme patterns. Excepting these two strains, restriction enzyme
      analysis of the chromosomal DNA of L. monocytogenes serotype 4b can discriminate
      serologically indistinguishable strains.

PMID- 9559442
TI  - Distribution of Rift Valley fever among cattle in Zambia.
AB  - In the present study, 1,421 cattle in 32 herds within nine districts, which are
      important cattle-producing centers in the nine provinces of Zambia, were tested
      for Rift Valley fever by the indirect immunofluorescence assay. One hundred and
      forty-seven cattle (10.5%) in 28 herds (88.9%) in the nine districts tested were
      positive for Rift Valley fever implying a country-wide distribution. In districts
      associated with flood plains and/or "dambos" (low lying areas of perpetual
      flooding), high herd and individual positive rates (100% and > 10%, respectively)
      were found, suggesting a significance of these features in the distribution of
      the disease.

PMID- 9559443
TI  - The effects of cyclosporin A on the polykaryocyte formation induced by measles
      virus in a monkey kidney cell line.
AB  - The effects of cyclosporin A (CsA) on the polykaryocyte formation induced by
      measles virus (MV) in a monkey kidney cell line (BSC-1) were studied. CsA
      inhibited virus-induced polykaryocyte formation as well as the production of
      infectious MV. The development of polykaryocyte formation in the presence of the
      CsA varied with virus strains, while pretreatment of the cells with 5 microM CsA
      for 24 hr before the virus infection enhanced polykaryocyte formation. These data
      demonstrated that CsA not only inhibits but also enhances virus-induced
      polykaryocyte formation depending on the conditions of its use.

PMID- 9559444
TI  - A comparison of young and aged populations for the diphtheria and tetanus
      antitoxin titers in Japan.
AB  - The antitoxin levels for diphtheria and tetanus were measured with samples of a
      young group immunized with diphtheria-tetanus-acellular pertussis combined
      vaccine and those of an aged group, members of which had not received vaccination
      in their youth. In the young group members of which had already received basic
      immunization with diphtheria-tetanus-acellular pertussis combined vaccine, the
      levels of both antitoxins rose well after injection at 11 to 12 years old with
      diphtheria-tetanus combined toxoids and remained high until 20 years of age. In
      the aged group, more than 80% showed antitoxin levels above 0.01 u/ml for
      diphtheria, while all had levels below that for tetanus, except three persons
      with confirmed tetanus immunization history. Maintenance of the protective
      antitoxin levels in the population by vaccination is necessary to prevent
      outbreaks of infection among unvaccinated or only partially immunized persons.

PMID- 9559445
TI  - Pulmonary manifestations of chronic heart failure.
AB  - These findings underscore the importance of understanding the complex
      interactions of multiple-organ systems in a chronic systemic disease state like
      congestive heart failure. The exaggerated ventilatory response in patients with
      heart failure is clearly multifactorial and it remains difficult to decipher
      whether this response results from or contributes to the sensation of dyspnea.
      Pulmonary dysfunction including ventilation-perfusion mismatching, decreased lung
      compliance, restriction, airway obstruction, decreased diffusion capacity, and
      decreases in respiratory muscle strength and endurance contribute to an
      inefficient breathing pattern and increased work of breathing. This is further
      compounded by the limited ability of the failing heart to meet the metabolic
      demands of the respiratory muscles, leading to under-perfusion and ischemia. This
      imbalance contributes to perceived dyspnea and exercise limitations.
      Understanding these physiologic cardiopulmonary interactions may lead to
      therapeutic modalities, such as respiratory muscle training, aimed at disrupting
      this intertwined cycle of events and improving functional capacity in patients
      with heart failure.

PMID- 9559446
TI  - Predictors of health-related quality of life with cardiac rehabilitation after
      acute myocardial infarction.
AB  - BACKGROUND: Health-related quality of life (HRQL) instruments provide valid and
      responsive outcome measures to assess the impact of disease and the response to
      interventions. However, they have not been applied widely to studies of
      rehabilitation after myocardial infarction. PURPOSE: To examine the extent to
      which baseline sociodemographic and clinical characteristics predict baseline and
      change in generic and specific HRQL. METHODS: A randomized controlled trial of an
      8-week cardiac rehabilitation intervention or usual care, with follow-up for 12
      months, in 201 patients with acute myocardial infarction (MI). Multiple
      regression analysis was used to identify predictors of HRQL. RESULTS: Specific
      HRQL scores and exercise tolerance improved significantly more in rehabilitation
      patients than usual care patients by the end of the 8-week intervention. All HRQL
      measures and exercise tolerance in both groups improved significantly during the
      12 month follow-up period but the differences between the groups were trivial. A
      poor baseline HRQL was the predominant predictor of improved generic and specific
      HRQL. Furthermore, greater improvement in HRQL consistently was associated with
      lower levels of cardiovascular risks such as absence of a previous MI or coronary
      artery bypass surgery, absence of angina, less smoking, and higher exercise
      tolerance. CONCLUSIONS: Improved generic and specific HRQL was associated with
      poorer baseline HRQL and less baseline cardiovascular risk. This reinforces the
      importance of addressing health behavior changes as soon as possible after MI and
      the usefulness of assessing both generic and specific HRQL in evaluating
      treatment effectiveness.

PMID- 9559447
TI  - The development and psychometric evaluation of the Pulmonary Functional Status
      Scale: an instrument to assess functional status in pulmonary disease.
AB  - BACKGROUND: This article describes the development and psychometric evaluation of
      the Pulmonary Functional Status Scale (PFSS). The PFSS was developed to address
      the need for a self-administered, disease-specific, functional status outcome
      measure that was conceptually based, relatively short, and comprehensively
      assessed the psychosocial domains affected by chronic pulmonary disease. METHODS:
      Content validity of the PFSS was established by a panel of experts. Construct
      validity was determined by principal components factor analysis using data from
      365 subjects derived from several studies that used the PFSS. The sample was
      predominantly white (80%), married (36%), and male (56%) with a mean age of 68.1
      years, mean forced expiratory volume in one second of 1.18 L and mean forced
      vital capacity of 2.31 L. Test-retest reliability was evaluated in 17 outpatients
      with chronic obstructive pulmonary disease. Concurrent validity was assessed by
      correlating responses on the total PFSS with the Sickness Impact Profile (SIP)
      score (n = 39), and the 12-minute walk test (n = 104). RESULTS: The factor
      structure solution used 35 of the 50 submitted items, explained 48.7% of the
      variance, and yielded three factors: Daily Activities/Social Functioning,
      Psychological Functioning, and Sexual Functioning. Cronbach's alpha coefficients
      for the total PFSS was 0.93 and the test-retest correlation coefficient was rho =
      0.75 (P = 0.001). The correlation between the total PFSS score and the SIP and 12
      minute walk test were r = -0.54 (P < 0.001) and r = 0.62 (P < 0.001),
      respectively. CONCLUSION: The PFSS has solid psychometric properties that make it
      acceptable for use in clinical practice as well as research.

PMID- 9559448
TI  - A new model for risk stratification and delivery of cardiovascular rehabilitation
      services in the long-term clinical management of patients with coronary artery
      disease.
AB  - This model for risk stratification includes variables that classify patients for
      Risk of Event similar to current models of risk stratification, as well as
      variables that stratify patients for Risk of Progression of Atherosclerosis by
      established risk factors. Categories of risk are established using accepted data
      from the literature for each risk factor that targets regression or plaque
      stabilization as the goal for Low Risk. A case-rate charging system and the
      proposed removal of time restrictions for length of cardiovascular rehabilitation
      fit neatly into the present climate for health care. Health maintenance
      organizations will be seeking programs that use similar models to address cost
      issues inherent in cardiovascular rehabilitation programs under current fee-for
      service models. Improved outcomes will also be targets for these programs and
      case-management lends itself to disease management, thus, improved outcomes.
      Tracking outcomes becomes even more important to both the provider and the
      insurer because results drive referrals. Likewise, removal of the time
      restriction for cardiovascular rehabilitation allows programs to individualize
      care and to target risk factors that are not only most deleterious, but also
      where patients show readiness for change. The changing environment of health care
      virtually mandates change in cardiovascular rehabilitation. It is imperative that
      programs manage the disease process, are effective in achieving outcomes that
      affect both patient function and the disease process, and are cost effective.
      This model for risk stratification and delivery of services addresses these
      requirements and provides a beginning for implementing these changes in
      cardiovascular rehabilitation.

PMID- 9559449
TI  - Helping older patients to cope with cardiac and pulmonary disease.
AB  - Family challenges, depression, and age-related developmental and psychological
      issues must be considered when structuring interventions for elder
      cardiopulmonary patients. Elderly patients tend to have difficulty coping when
      they face novel, unpredictable circumstances and are left to flounder in
      suspenseful anticipation. Furthermore, if support is not forthcoming during such
      times--or if they are treated in ways that strip them of control rather than in
      ways that bolster their sense of control--elderly patients are at great risk of
      quickly developing a passive, learned helplessness that can significantly
      complicate their rehabilitation. The overall well-being of elderly
      cardiopulmonary patients is affected by more than the actions of health-care
      providers. Poverty, pension and health-care plans, institutionalization,
      concomitant diseases, family issues, and other factors have a profound and,
      frequently, an overriding effect on the functional status of the elderly
      population. However, it is also true that the provision of spirit-enhancing care
      can make a tremendous difference in quality of life for elderly patients,
      independent of factors such as residential circumstance or health status. The
      most valued and valuable sources of social support for elderly patients come from
      family, church, and health-care providers. Our interventions either enhance or
      diminish an elderly patient's sense of autonomy and control. Our task-driven
      health-care system, replete with its growing emphasis on brevity of treatments
      and cost-effectiveness, can create a style and pace of delivering care that
      demoralizes an elderly patient. The results can be devastating: "When the spirit
      is broken, one has no will to marshall coping skills". But health-care providers
      who are attuned to the psychosocial issues relevant to the later life stages can
      make a profound difference in enhancing both rehabilitation and quality of life
      for elderly cardiopulmonary patients and their loved ones.

PMID- 9559450
TI  - Impact of steady-state and exercise modality on estimating oxygen consumption in
      men with and without coronary artery disease.
AB  - PURPOSE: This study examined the effect of steady-state on the ability of 15 men
      with coronary artery disease (CAD) and 13 men without CAD disease (non-CAD) to
      reach a rate of oxygen consumption (VO2) relative to population norms during
      treadmill and cycle ergometry exercise testing. METHODS: Subjects completed a
      maximal graded exercise test on the treadmill and cycle ergometry involving 3
      minute stages and a submaximal exercise test involving 6-minute stages to 80% of
      maximal effort. Estimates of VO2 were derived from commonly cited clinical
      estimation equations. RESULTS: Only the Foster equation accurately estimated
      maximal VO2 during a treadmill graded exercise test in patients with CAD.
      However, each of cited clinical equations accurately estimated maximal VO2 during
      a treadmill graded exercise test in the non-CAD group. No equation accurately
      estimated VO2 at submaximal efforts during treadmill exercise for either group.
      Cycle ergometry estimation equations accurately estimated VO2 in both groups at
      maximal effort, but were inconsistent at submaximal efforts. Both the CAD and the
      non-CAD group reached steady-state VO2 within 3 minutes, at submaximal workloads.
      CONCLUSIONS: The inability to attain an expected VO2 during exercise did not seem
      related to steady-state VO2 because both CAD and non-CAD groups readily reached
      steady-state VO2, though the estimation of VO2 remained inaccurate for most
      treadmill estimation equations. Because VO2 was accurately estimated for cycle
      ergometry exercise, estimation accuracy seems to be influenced by exercise
      modality.

PMID- 9559451
TI  - The assessment of recovery in patients after myocardial infarction using three
      generic quality-of-life measures.
AB  - BACKGROUND: To evaluate the sensitivity to change of three generic quality-of
      life measures in patients after myocardial infarction (MI). METHODS: Patients
      admitted to the Coronary Care Unit of Royal Devon and Exeter Healthcare Trust
      over a 9-month period were selected on the basis of a first MI and under 80 years
      of age. Quality of life was assessed 6 weeks and 6 months after MI using the
      Sickness Impact Profile (SIP), Nottingham Health Profile (NHP), and McMaster
      Health Inventory Questionnaire (MHIQ). An index of whether these measures are
      sensitive to change over time was determined by dividing the mean change from 6
      weeks to 6 months of each instrument subscale by the baseline standard deviation
      of that subscale. Values of 0.2, 0.5, and 0.8 and above represent modest,
      moderate, and good sensitivity, respectively. RESULTS: Eighty-eight patients
      completed and returned the quality-of-life measures at both 6 weeks and 6 months.
      Four SIP subscales achieved a sensitivity to change index of 0.20 to 0.50: body
      care and movement, emotional behavior, work, and eating. Other SIP, NHP, and MHIQ
      subscales showed sensitivity index values of less than 0.20. No sensitivity index
      values of 0.50 or more were observed. CONCLUSIONS: During the period of this
      study, all three generic quality-of-life measures displayed only modest levels of
      sensitivity to change. Other quality-of-life measures need to be developed for
      the assessment of cardiac patients. This is particularly important when choosing
      suitable quality-of-life measures to assess cardiac rehabilitation.

PMID- 9559453
TI  - Format for reporting refractive surgical data.

PMID- 9559452
TI  - Circuit weight training in cardiac patients: determining optimal workloads for
      safety and energy expenditure.
AB  - BACKGROUND: While most studies suggest circuit weight training (CWT) to be safe
      in cardiac rehabilitation populations, few investigators have controlled
      variables known to impact CWT intensity. Therefore, the purposes of this study
      were to determine the energy cost and evaluate safety of cardiac patients while
      varying rest interval duration and lifting load in a CWT format. METHODS: Nine
      male subjects with documented coronary artery disease had maximal oxygen uptake
      (VO2max), one-repetition maximum (1-RM), and body composition tested. In random
      order and on separate days, 4 CWT sessions using either 40% or 60% of the 1-RM,
      and either 30 or 60 seconds of rest between stations were completed. Energy cost,
      heart rate (HR), blood pressure (BP), and rate-pressure product (RPP) were
      measured. Data were analyzed with a repeated measures analysis of variance, and
      Tukey's post-hoc test was performed when significant results were found. The
      alpha level was set at < .05. RESULTS: Subjects exercised at 25% to 32% of VO2max
      (58%-67% of HRmax) during CWT. The HR and RPP responses were lower during all CWT
      protocols than at 85% of the treadmill VO2max. No subject displayed any ST
      segment depression or angina during CWT. The 40%-60-second protocol had an energy
      cost (2.98 kcal/min) that was lower (P < .05) than the other protocols (3.48-3.81
      kcal/min). Increasing the lifting load resulted in increases (P < .05) in energy
      cost, and decreasing the rest interval increased energy cost only during the 40%
      1-RM protocols. CONCLUSIONS: Results indicate that CWT protocols of varied
      intensity are safe for cardiac patients when compared to treadmill exercise, and
      changes in rest interval duration and load can impact the energy cost.

PMID- 9559454
TI  - Ophthalmologic biocompatibility: anachronism or oxymoron?

PMID- 9559455
TI  - Screening for pupil size in prospective refractive surgery patients.

PMID- 9559456
TI  - Screening for pupil size in prospective refractive surgery patients.

PMID- 9559457
TI  - Screening for pupil size in prospective refractive surgery patients.

PMID- 9559458
TI  - Screening for pupil size in prospective refractive surgery patients.

PMID- 9559459
TI  - Screening for pupil size in prospective refractive surgery patients.

PMID- 9559460
TI  - Screening for pupil size in prospective refractive surgery patients.

PMID- 9559461
TI  - Consultation section. Refractive surgical problem.

PMID- 9559462
TI  - Managing inferior zonule tears during manual extracapsular cataract extraction.
AB  - We describe a new technique for safely concluding manual extracapsular cataract
      extraction in the presence of a rupture of the interior zonules. A lens glide is
      inserted in the anterior chamber. The tip of the glide is placed in the inferior
      part of the capsular bag, pushing it toward the ciliary sulcus at 6 o'clock. The
      extraocular part of the glide is sutured to the sclera to prevent its
      displacement during manipulation of the eye. The glide spreads the rolled
      inferior capsule, allowing aspiration of retained cortical material and in-the
      bag intraocular lens implantation. The glide is then removed. This technique was
      used in 12 eyes with pseudoexfoliation in which the complication occurred. No
      vitreous loss, lens displacement, or other intraoperative or postoperative
      complications were observed.

PMID- 9559463
TI  - Photorefractive keratectomy for residual myopia after radial keratotomy. PRK
      After RK Study Group.
AB  - PURPOSE: To evaluate the visual outcomes in patients having photorefractive
      keratectomy (PRK) to correct residual myopia after radial keratotomy (RK).
      SETTING: Nine refractive surgery centers in the United States and one in South
      Korea. METHODS: This retrospective analysis comprised 38 eyes of 32 patients
      treated with PRK after RK and followed for 12 months. Analysis was based on pre
      RK and pre-PRK refraction as well as response to RK (pre-RK minus pre-PRK
      refractions). RESULTS: Mean pre-RK and pre-PRK refractions were -8.11 diopters
      (D) +/- 2.92 (SD) and -4.28 +/- 2.08 D, respectively. One month after PRK, mean
      refraction was +0.42 +/- 1.56 D and regressed to -0.95 +/- 1.24 D at 12 months.
      At 12 months, 65% of eyes had an uncorrected visual acuity of 20/40 or worse, and
      11.1% lost 2 or more lines of best corrected acuity. Of eyes with an original
      erro of -6.00 or less, 81.8% were within +/- 1.00 D of intended correction at 12
      months and of those with an original error of -9.12 to -20.00 D 50.0% (P = .004).
      All eyes with residual (pre-PRK) errors of -3.00 D or less and 42.9% with a
      residual error of -6.12 to -9.00 D were within +/- 1.00 D of intended correction
      (P = .07). There were no statistically significant differences in the response to
      PRK between eyes that had an RK response of 0 to 3.00, 3.12 to 6.00, or 6.12 to
      12.00 D. CONCLUSION: Patients with lower original and residual myopia achieved
      better visual outcomes after PRK than those with higher myopia. The amount of
      myopic correction achieved using RK was not predictive of the amount of myopic
      correction using PRK.

PMID- 9559464
TI  - Predictability of radial keratotomy after excimer laser photorefractive
      keratectomy.
AB  - PURPOSE: To evaluate the results of radial keratotomy (RK) after photorefractive
      keratectomy (PRK). SETTING: London Centre for Refractive Surgery. METHODS: This
      study comprised six eyes having RK enhancement after PRK. Outcome measures were
      the effect of the incisions on post-PRK haze and best corrected visual acuity
      (BCVA), predictability of the result on already flattened corneas, and the
      validity of standard radial keratotomy (RK) nomograms. All PRKs were done when
      refraction was stable with one of two VISX lasers: the Twenty-Twenty or Star.
      Mean follow-up was 14 months. RESULTS: All eyes had further corneal flattening.
      The standard RK nomograms were deemed appropriate. There was no loss of BCVA
      because of aggravated haze of irregular astigmatism. CONCLUSION: Radial
      keratotomy after PRK proved safe, economical, and effective after PRK in six
      eyes.

PMID- 9559465
TI  - Radial keratotomy for residual myopia after photorefractive keratectomy.
AB  - PURPOSE: To evaluate the safety, efficacy, and complications of radial keratotomy
      (RK) after photorefractive keratectomy (PRK) for myopia. SETTING: Laser
      Ultravision Institute. Montreal, Canada. METHODS: Surgically induced refractive
      and visual acuity changes were retrospectively evaluated in 14 eyes of 10
      patients treated with RK after PRK. All patients had simple myopia or compound
      myopic astigmatism. Minimum follow-up was 6 months. RESULTS: Three eyes (21%) had
      one PRK, 7 (50%) had two treatments, and 4 (29%) had three. Eleven eyes (79%)
      required four-incision RK and 3 (21%), eight-incision RK. All patients had
      improved uncorrected visual acuity. Six months after the RK retreatment, there
      was a significant reduction in spherical equivalent of 2.93 diopters +/- 1.53
      (SD) (P < .05). No intraoperative or postoperative complications occurred except
      overcorrection (two cases). CONCLUSION: Radial keratotomy is an effective, safe
      method for treating undercorrected myopia after PRK. Further study and analysis
      of this series of patients are planned.

PMID- 9559466
TI  - Prompt re-treatment after photorefractive keratectomy.
AB  - PURPOSE: To study eyes that received a photorefractive keratectomy (PRK)
      retreatment 1 to 4 months after the first treatment and describe refractive
      stability and complications. SETTING: Michael Pop CLinics, Montreal, Canada.
      METHODS: Twenty-six eyes of 20 patients were re-treated for undercorrection and,
      regression with or without haze. Postoperative refractions were performed at 1,
      2, 3, and 6 months. Haze was evaluated on a scale of 0 to 4. RESULTS: Ninety
      percent of the 21 eyes followed for 6 months after re-treatment achieved an
      uncorrected visual acuity of 20/40. At 6 months, 67 and 95% of eyes were within
      +/- 0.50 diopter (D) and +/- 1.00 D, respectively. Regression between 1 and 6
      months after re-treatment was 0.71 D, which represented less than one half that
      observed after the initial treatment. Six months after re-treatment, haze
      decreased by half, and no eye had haze above 1. Best corrected visual acuity
      (BCVA) before treatment was well correlated with values 6 months after re
      treatment (P < .001). At 6 months, 1 eye lost two lines of BCVA but had an acuity
      of 20/30 and 2 eyes lost one line of BCVA. CONCLUSION: Prompt re-treatment after
      PRK for myopia allowed management of undercorrections and regressions with low
      morbidity and high refractive stability. By re-treating promptly, no additional
      complications were created and patients avoided long periods of unsatisfactory
      vision.

PMID- 9559467
TI  - Photorefractive keratectomy for pediatric myopic anisometropia.
AB  - PURPOSE: To evaluate the visual results of excimer laser photorefractive
      keratectomy (PRK) to treat pediatric patients with amblyopic myopic anisometropia
      in whom conventional amblyopia treatments have failed. SETTING: Instituto
      Oftalmologico de Alicante, University of Alicante, Spain. METHODS: Six patients
      aged 5 to 7 years with amblyopic myopic anisometropia were treated by PRK in the
      more myopic eye using a VISX Twenty-Twenty excimer laser. Minimum preoperative
      refraction in the amblyopic eyes ranged from -4.00 to -13.00 diopters and best
      corrected visual acuity (BCVA), from 20/40 to 20/400. All cases completed a
      minimum of 2 years follow-up of antiamblyopic treatment. RESULTS: After PRK,
      preoperative BCVA was maintained without optical correction and complementary
      refraction resulted in increased BCVA in every case. One patient with high myopia
      developed severe haze. There were no other significant complications. CONCLUSION:
      Our results indicate that PRK may be an alternative for the correction of
      pediatric myopic anisometropia and an important aid in treating amblyopia. When
      other therapies have failed, using PRK in children of the ages in this study must
      be carefully evaluated; however, our results suggest a beneficial effect.

PMID- 9559468
TI  - Corneal infection after radial keratotomy.
AB  - PURPOSE: To evaluate nine eyes that developed corneal infection after radial
      keratotomy (RK) and their subsequent management. SETTING: Dr. Rajendra Prasad
      Centre for Ophthalmic Sciences, New Delhi, India. METHOD: The parameters
      evaluated were interval between RK and development of the ulcer, number of
      keratotomy incisions, nature of surgery (primary or secondary), status at
      presentation, and best corrected visual acuity (BCVA). Corneal scrapings were
      taken from all eyes for microbiological evaluation. Initial therapy was based on
      clinical impression and subsequent therapy, on the microbiological report.
      RESULTS: Staphylococcus species were the most frequently isolated bacteria
      followed by Pseudomonas aeruginosa. Two eyes had fungal growth, and no organisms
      were isolated from one. All but one eye responded to medical therapy; healing
      took 23 to 26 days. Therapeutic penetrating keratoplasty (PKP) was done in one
      eye. Presenting BCVA of hand movement to 6/36 improved to hand movement to 6/18
      after the ulcer healed. Final BCVA was 6/36 to 6/9 after lamellar keratoplasty or
      PKP or with contact lens of spectacle correction. CONCLUSION: Our study shows
      that corneal infection is a potential complication of RK. Therefore, persistent
      postoperative irritation should be carefully observed to ensure early diagnosis
      and prompt therapy.

PMID- 9559469
TI  - Factors that influence patient choice of an excimer laser treatment center.
AB  - PURPOSE: To identify the factors that most influenced patient choice of an
      excimer laser treatment center and those most likely to deter patients from
      selecting a particular center. SETTING: A National Health Service (NHS) excimer
      laser unit in the northeast of England. METHODS: An anonymous 24-item
      questionnaire was constructed. Each question had a visual analogue scale,
      anchored at each end with an adjectival description. Patients were asked to mark
      their response to the related question on the scale. Using the database of over
      300 patients treated by excimer laser photorefractive keratectomy (PRK) at
      Sunderland Eye infirmary between May 1993 and December 1995, the first 140
      consecutive patients were identified. Questionnaires were sent to them and
      returned between August 1 and October 31, 1995. RESULTS: A 64.3% reply rate (90
      patients) was achieved. Overall, the results suggest that patients considered
      many factors to be important in their selection of a treatment center for PRK
      correction of myopia. Over 95% said that treatment and review by a consultant
      ophthalmologist, comprehensive follow-up appointments, professional attitude by
      staff, and reputation of the hospital were important factors in their selection
      of the center. Ninety to 95% said confidence in the clinical reputation and
      skills of the ophthalmic surgeons performing the treatment was important, as was
      having follow-up by only one or two staff members. Slightly more than 50% said
      that being treated in an NHS hospital setting (51.7%) or that expense of the
      treatment (50.5%) were important factors in their decision. CONCLUSION: Patients
      who chose to have excimer laser PRK based their choice of a unit on reputation of
      the staff and hospital but also on having care and follow-up by a consultant
      ophthalmic surgeon, high standards of equipment, continuity of care, and a
      comprehensive review system backed up by ready accessibility to staff members.
      Although proximity of a unit was important, cost appeared less important than the
      other factors.

PMID- 9559470
TI  - Contact-angle analysis of intraocular lenses.
AB  - PURPOSE: To present contact-angle measurements of commercially available
      intraocular lenses (IOLs) in air and in water to facilitate the understanding of
      how various IOLs might interact in different environments. SETTING: Laboratory.
      METHODS: Five commercially available IOLs were studied: AMO DuraLens PS-59NB. AMO
      PhacoFlex SI-26NB, AMO PhacoFlex II SI-30NB, Chiron ChiroFlex C10UB, and Alcon
      AcrySof MA60BM. The AMO soft acrylic model AR40, currently under clinical study,
      was also evaluated. Contact-angle measurements were made in air and in water
      using sessile drop and captive bubble methods. RESULTS: The sessile drop method
      indicated that all materials were hydrophobic in air. The captive bubble method
      differentiated materials based on their polar and dispersive forces. CONCLUSION:
      Contact-angle measurements differed depending on the test conditions. Proper
      choice of contact-angle measurement method can generate useful information about
      a material surface and its potential biomaterial interactions.

PMID- 9559471
TI  - Relationship between intraocular lens biomaterials and posterior capsule
      opacification.
AB  - PURPOSE: To determine whether posterior capsule opacification (PCO) is influenced
      by intraocular lens (IOL) material. SETTING: A British teaching hospital eye
      department. METHODS: Ninety eyes were prospectively randomized to receive a
      poly(methyl methacrylate) (PMMA), silicone, or AcrySof IOL. All lenses had 6.0 mm
      optics and PMMA haptics. A standardized surgical protocol was performed by a
      single surgeon using an extracapsular technique with capsulorhexis. Patients
      having surgical complications were excluded and all patients had standardized
      medication and follow-up. Posterior capsule opacification was assessed by a
      digital retroillumination camera using a dedicated software program based on the
      analysis of texture in the image and calculated as the percentage area of
      opacified capsule. Data were analyzed 2 years postoperatively. RESULTS: There was
      a significant difference in percentage of PCO at 2 years among the three lens
      types (P < .0001). The AcrySof lenses were associated with less PCO (median
      11.75%) than PMMA (43.65%) and silicone (33.50%) lenses (P < .001 and P = .025,
      respectively). The difference between PMMA and silicone lenses was not
      statistically significant. CONCLUSION: Intraocular lenses made from AcrySof were
      associated with a significantly reduced degree of PCO.

PMID- 9559473
TI  - Adhesiveness of AcrySof to a collagen film.
AB  - PURPOSE: To measure the adhesiveness of the AcrySof intraocular lens (IOL) to a
      collagen film to ascertain its capacity to adhere to the lens capsule. SETTING:
      Haibara General Hospital, Haibara, and Hamamatsu University School of Medicine,
      Hamamatsu, Shizuoka, Japan. METHODS: Each of five AcrySof IOLs was attached to a
      collagen film, slightly pressed in intraocular irrigating solution, and then
      pulled up and off the film with a DuNouy's surface balance. The force recorded by
      the surface balance at the moment it detached from the film was defined as the
      lens' adhesiveness. A control experiment was performed using five conventional
      poly(methyl methacrylate) (PMMA) IOLs. RESULTS: Mean adhesiveness was 2.76 gram
      weight (gw) +/- 0.55 (SD) for AcrySof and 0.81 +/- 0.20 gw for PMMA. The
      difference was statistically significant (P < .0001, t-test). CONCLUSION: AcrySof
      may have a strong tendency to adhere to the lens capsule, contributing to
      posterior and anterior capsule clarity and preventing lens decentration in vivo.

PMID- 9559472
TI  - Biocompatibility of poly(methyl methacrylate), silicone, and AcrySof intraocular
      lenses: randomized comparison of the cellular reaction on the anterior lens
      surface.
AB  - PURPOSE: To determine the foreign-body response to three intraocular lens (IOL)
      biomaterials (poly[methyl methacrylate] [PMMA], silicone, and AcrySof) and use
      this as an indicator of their comparative biocompatibility postoperatively within
      the eye. SETTING: A British teaching hospital eye department. METHODS: Ninety
      eyes were prospectively randomized to receive a PMMA, silicone, or AcrySof IOL.
      All lenses had 6.0 mm optics with PMMA haptics. A standardized surgical protocol
      was performed by a single surgeon using an extracapsular technique with
      capsulorhexis; eyes that experienced a surgical complication were excluded. All
      patients had standardized postoperative medication and follow-up. Specular
      microscopy of the anterior IOL surface was carried out after pupil dilation on
      days 1, 7, 30, 90, 180, 360, and 720 to assess small cell and giant cell
      reactions. RESULTS: All three IOL types produced a mild degree of nonspecific
      foreign-body response, which resolved over the study period without detrimental
      effect. The silicone group had significantly higher small cell counts than the
      PMMA and AcrySof groups (P = .02); the AcrySof group had significantly lower
      giant cell counts than the other two groups (P = .003). CONCLUSION: The three IOL
      types were sufficiently biocompatible to function in normal eyes with age-related
      cataracts. However, AcrySof IOLs were associated with lower giant cell counts
      than PMMA and silicone IOLs and might produce better results in eyes with pre
      existing blood-aqueous barrier damage.

PMID- 9559474
TI  - In vivo study of a fluorocarbon polymer-coated intraocular lens in a rabbit
      model.
AB  - PURPOSE: To evaluate the biocompatibility in rabbit eyes of poly(methyl
      methacrylate) (PMMA) intraocular lenses (IOLs) that were surface modified using
      Teflon AF. SETTING: Hotel-Dieu Hospital, Paris Cedex, France. METHODS: The IOLs
      were coated with Teflon AF, an amorphous, transparent, and highly hydrophobic
      fluorocarbon polymer, by immersing them in Teflon AF 5% and evaporating the
      solvent (C8F18). The surface quality of the Teflon-coated IOLs was evaluated by
      scanning electron microscopy (SEM). Teflon-coated (n = 20) and control PMMA (n =
      10) IOLs were implanted in rabbit eyes. The presence of iris-IOL synechias and
      the number of deposits on the IOL surfaces were clinically evaluated in both
      groups to assess the antiadhesive effect of Teflon AF. The Teflon-coated IOLs
      were removed, their surfaces were evaluated by SEM, and their elemental
      composition was checked by EDXA and Raman spectrometry. RESULTS: The PMMA IOLs
      were completely coated with Teflon AF. The Teflon group had no iris-IOL synechias
      and the control group, two extensive synechias. There were significantly fewer
      deposits on the surfaces of Teflon-coated IOLs than on the control IOLs 30 and 60
      days postoperatively (P < .0001). Scanning electron microscopy showed lens
      epithelium proliferation and spindle-shaped cells on the surfaces of the PMMA
      IOLs and cell deposits on the irregular regions of the Teflon-coated IOLs. White
      yellow spots were present on the surfaces of both IOL types. The elemental
      composition of Teflon-coated IOLs was stable. CONCLUSION: Teflon AF had an
      antiadhesive effect that increased the biocompatibility of PMMA IOLs in vivo.

PMID- 9559475
TI  - Biocompatibility and blood-aqueous barrier impairment in at-risk eyes with
      heparin-surface-modified or unmodified lenses.
AB  - PURPOSE: To evaluated the influence of heparin-surface-modified (HSM) versus
      unmodified poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) on the
      blood-aqueous barrier (BAB) in at-risk eyes. SETTING: Department of
      Ophthalmology, Bundesknappschaft's Hospital, Sulzbach Germany. METHODS: This
      study comprised 100 patients with predisposing risk factors for BAB
      destabilization (e.g., diabetes mellitus with or without retinopathy, glaucoma,
      pseudoexfoliation, uveitis). One eye in each patient received an HSM IOL and the
      fellow eye, a conventional unmodified PMMA IOL after phacoemulsification by the
      same surgeon. Anterior chamber flare was measured with the Kowa 500 laser flare
      meter 1 day before and 1 day, 1 and 6 weeks, and 3 months after surgery. RESULTS:
      For most risk factors, mean flare was lower in the HSM group than in the PMMA
      group at most follow-ups. Significantly lower flare values (difference between
      postoperative and preoperative mean values) were seen in eyes with the HSM IOL at
      6 weeks (P < .004) and 3 months (P < .003; Student's t-test). In the group with
      preoperative elevated flare values, the eyes with the HSM IOL had significantly
      better results 6 weeks (P < .0006) and 3 months (P < .01) postoperatively. The
      values in the HSM IOL eyes were also significantly higher in the diabetic with
      retinopathy group at 3 months (P < .003). CONCLUSION: The results confirm the
      efficacy of IOL surface modification in reducing postoperative intraocular
      reaction in at-risk eyes.

PMID- 9559476
TI  - Low-vacuum, low-voltage scanning electron microscopy of poly(methyl methacrylate)
      intraocular lenses.
AB  - PURPOSE: To evaluate the usefulness of low-vacuum, low-voltage scanning electron
      microscopy (LVSEM) in examining the surfaces of intraocular lenses (IOLs) without
      preparation. SETTING: In vitro laboratory experiment. METHODS: Six commercially
      available IOLs made of poly(methyl methacrylate) (PMMA) and one explanted PMMA
      IOL were evaluated with LVSEM without sputter coating. Sham surgical maneuvers
      were performed on some IOLs and the surface changes observed. RESULTS: Smooth
      surfaces of IOL optics and haptics, relatively sharp edges of optic holes, and
      irregularities at the optic/haptic junction were clearly observed. Crystalline
      deposits were seen on the surfaces after the IOLs were dipped and dried in saline
      solution. Scratches and marks were observed after they were grasped with a
      forceps. CONCLUSIONS: Low-vacuum, low-voltage scanning electron microscopy is a
      time-saving procedure that can be used by inexperienced investigators. The
      resolution under relatively low magnification appeared to be satisfactory for
      evaluating the IOL surface.

PMID- 9559477
TI  - Analysis of zonular-free zone and lens size in relation to axial length of eye
      with age.
AB  - PURPOSE: To evaluate the anatomical relationships of the zonular-free zone (ZFZ)
      of the anterior capsule and crystalline lens diameter in relation to the axial
      length of the eye with age. SETTING: Department of Ophthalmology, Yonsei
      University College of Medicine, Seoul, Korea, and Storm Eye Institute, Medical
      University of South Carolina, Charleston, South Carolina, USA. METHOD: Various
      ocular structures in 122 eyes obtained post-mortem were measured without prior
      preparation. The correlation between age, anterior-posterior (A-P) length and
      globe size, and diameters of the cornea, crystalline lens, and ZFZ were analyzed.
      RESULTS: The average A-P globe length, and corneal, lens, and ZFZ diameters were
      24.48, 11.67, 9.65, and 6.93 mm, respectively. There was no significant
      relationship between A-P length and globe size and corneal diameter in different
      age groups. The ZFZ size varied negligibly among age groups. There was a
      statistically significant correlation between lens diameter and age (correlation
      coefficient = 0.2647; P < .01) and lens diameter and A-P globe length
      (correlation coefficient = 0.3183; P < .001). CONCLUSIONS: When choosing an
      intraocular lens, one should consider the patient's age and the A-P globe length.
      Six eyes (5%) showed unusual anterior insertion of zonular attachment, which
      reminds us to be prudent with a large paracentral capsulorhexis.

PMID- 9559478
TI  - Ideal size of an intraocular lens for capsular bag fixation.
AB  - PURPOSE: To determine the ideal size of an intraocular lens (IOL) for proper
      capsular bag fixation in different sizes of evacuated capsular bags. SETTING:
      Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea,
      and Storm Eye Institute Medical University of South Carolina, Charleston, South
      Carolina, USA. METHODS: Fifteen eyes obtained post-mortem were divided by
      crystalline lens size into three groups. Intraocular lenses of five different
      sizes were implanted in each capsular bag. The arc of contact between the haptics
      and capsular equator and the capsular bag distortion with each IOL were measured
      and compared using posterior-view analysis. RESULTS: The arc of contact was
      directly proportional to the IOL size and inversely related to the lens size. The
      smallest arc of contact was 2.0 mm with the smallest IOL implanted in the largest
      lens group. The maximum capsular bag distortion was 2.6 mm in the case of the
      largest IOL implantation in the smallest lens group. CONCLUSION: Implanting an
      IOL smaller than 12.5 mm in a large capsular bag can result in unstable fixation,
      while implanting an IOL larger than 12.5 mm in a small capsular bag can result in
      excessive stretching and distortion of the capsular bag and surrounding zonules.

PMID- 9559479
TI  - Topical versus peribulbar anesthesia, without sedation, for clear corneal
      phacoemulsification.
AB  - PURPOSE: To investigate patient and surgeon acceptance of topical anesthesia as
      an alternative to peribulbar anesthesia for clear corneal phacoemulsification.
      SETTING: Department of Ophthalmology, Whipps Cross Hospital, London, England.
      METHODS: All cataract surgery was performed using a temporal clear corneal
      approach, bimanual phacoemulsification, and in-the-bag intraocular lens
      implantation. The results of 51 patients having surgery under topical anesthesia
      (amethocaine) were compared with those of 30 patients having peribulbar
      anesthesia (50:50 mixture of lignocaine 2% and bupivacaine 0.5% with
      hyaluronidase). No sedation was used in either group. Pain perception on
      administration of the anesthetic, perioperatively (period immediately surrounding
      and during surgery), and postoperatively was assessed using a visual analog scale
      from 0 to 10 (0 = no pain: 10 = worst pain imaginable). A questionnaire was used
      to assess the degree of patient and surgeon satisfaction. RESULTS: Administration
      of topical amethocaine was significantly less painful than peribulbar bupivacaine
      (P = .03). Perioperative pain showed a trend toward being worse in the topical
      anesthesia group but did not reach statistical significance. There was no
      difference in the postoperative pain scores of the two groups. The surgical
      experience was rated very satisfactory by 67% in the topical group and 73% in the
      peribulbar group. The surgeons reported no difficulties or complications.
      CONCLUSION: Topical anesthesia was safe and effective for clear corneal
      phacoemulsification and was well tolerated by patients. The slightly greater
      awareness of ocular discomfort in the topical group perioperatively did not alter
      patient satisfaction with the surgical experience when compared with the
      peribulbar group.

PMID- 9559480
TI  - Validation of a handheld automated keratometer in adults.
AB  - PURPOSE: To evaluate the Nidek handheld automated keratometer and compare it with
      the manual Zeiss keratometer. SETTING: St. Paul's Eye Unit, Royal Liverpool
      University Hospital, Liverpool, United Kingdom. METHODS: Forty-five normal adult
      volunteers were included in the study. Three sets of randomized keratometry
      measurements were taken from both eyes of each adult, with both instruments by
      two independent observers. Readings included powers of the steep and flat
      meridians and axis of the flat meridian. The mean difference between the two
      instruments was calculated. The variance of each instrument was calculated for
      the axis, the steep and flat meridians, and the mean of the two meridians.
      RESULTS: There was no significant difference between the mean Nidek and Zeiss
      keratometry readings for the steep (0.015 mm; P = .167) or flat (0.054 mm; P =
      .069) meridian or axis measurements (P = .172). On repeated measurements, the
      within-subject and within-group variabilities, calculated separately for each
      instrument, were significantly less for the Nidek automated keratometer than the
      Zeiss keratometer (P < .01) when measuring the steep and flat meridians. There
      was however, a significant increase in axis variability using the Nidek
      keratometer (range 20 degrees; P < .01). CONCLUSION: The Nidek automated
      keratometer was accurate, reliable, and easy to use and compared favorably with
      the manual Zeiss keratometer when measuring corneal curvature. In the handheld
      mode, the Nidek is not suitable for axis measurements. It has the additional
      advantage of portability.

PMID- 9559481
TI  - Compression forces of haptics of freely rotating posterior chamber intraocular
      lenses.
AB  - PURPOSE: To measure the compressive forces of the haptics of 28 intraocular lens
      (IOL) models for different modes of compression and compare the results of two
      types of measurements. SETTING: Department of Ophthalmology, Central Hospital of
      Central Finland, Jyvaskyla, Finland. METHODS: The haptics of 28 types of IOLs
      were compressed to a diameter of 9.0 mm between curved anvils. The compression
      forces in the plane of compression (i.e., in the plane of the optics) were
      measured at 0.5 mm intervals. During compression, the optics and the haptics were
      free to rotate with respect to the anvils. The results were compared with those
      of earlier measurements in which the optics were held fixed during compression.
      Perpendicular forces were measured at 0.4 mm intervals. RESULTS: The measured
      forces in the plane of the optics varied between 114 and 659 mg at a diameter of
      10.0 mm and 192 and 1047 mg at a diameter of 9.0 mm. When compressed to 10.0 mm
      in diameter, the forces were 1 to 75% lower than when lens rotation was not
      possible. The forces perpendicular to the optic varied between 0 and 96 mg at a
      10.0 mm diameter and correlated with the forces in the plane of the optic.
      CONCLUSION: The compression forces of the lens haptics were generally lower when
      the lenses were allowed to rotate during compression. The orders of stiffness of
      the haptics in these two measurements were similar. The perpendicular forces were
      generally small and correlated significantly with the forces measured in the
      plane of the optic.

PMID- 9559482
TI  - Effects of a large supper on glucose levels the following morning in patients
      with type 2 diabetes.
AB  - Seventeen patients were studied to test the hypothesis that a large evening meal
      influences the fasting glucose level and glucose tolerance the following morning
      in patients with type 2 diabetes. Oral hypoglycemic agents were discontinued for
      2 weeks. The baseline fasting plasma glucose levels were 12.3 +/- 0.9 mmol/L.
      Fasting and postprandial (post-Sustacal) glucose, insulin, and C-peptide
      measurements were performed the morning after the patients received three
      separate meal protocols spaced 1 week apart. The caloric distribution of the meal
      protocols was (1) 7 kcal/kg of ideal body weight breakfast and lunch and 14
      kcal/kg supper (small supper); (2) 7 kcal/kg breakfast and lunch and 28 kcal/kg
      for supper (large supper); and (3) 14 kcal/kg breakfast and lunch (no supper).
      Fasting glucose level were higher the morning after the large supper compared to
      no supper (13.6 +/- 0.7 versus 12.3 +/- 0.5 mmol/L, p < 0.05) and also to the
      small supper (13.6 +/- 0.7 versus 12.5 +/- 0.6 mmol/L, p = 0.05). No difference
      was observed in the fasting glucose levels between the small supper and no supper
      (p > 0.2). The fasting insulin and C-peptide levels, and the post-Sustacal areas
      under the curve of glucose, insulin, and C-peptide did not differ among the
      meals. In patients with type 2 diabetes, a large evening meal is associated with
      a modest elevation in fasting glucose the following morning.

PMID- 9559483
TI  - Cilazapril and dietary gamma-linolenic acid prevent the deficit in sciatic nerve
      conduction velocity in the streptozotocin diabetic rat.
AB  - Young adult male Hooded Wistar rats were rendered diabetic by administration of
      streptozotocin and maintained for 5 weeks on a diet containing either 6% olive
      oil as the total source of fat (OO diet), or purified gamma-linolenic acid (GLA)
      at a concentration of 0.5% with the remaining 5.5% provided by olive oil (GLA
      diet). Rats were treated with the angiotensin converting inhibitor, cilazapril,
      administered in the drinking water at a dose of 20 mg kg-1 body weight day-1. For
      the OO diet groups, sciatic nerve conduction velocity (NCV) in diabetic rats was
      reduced by 32% (p < 0.01) in comparison with nondiabetic (vehicle-treated) rats
      and 27.5% (p < 0.05) in comparison with diabetic rats treated with cilazapril.
      Diabetic, cilazapril-treated rats showed no reduction in NCV. For the
      nondiabetic, diabetic, and diabetic plus cilazapril groups fed GLA, the NCV was
      not significantly different, indicating that dietary GLA also prevented the
      deficit in the NCV induced by the diabetic state. Analysis of the sciatic nerve
      endoneurial phospholipid fatty acids revealed a significant reduction in the
      proportion of GLA and an elevation in the proportion of linoleic acid in the
      diabetic groups compared with the nondiabetic groups and this was independent of
      the cilazapril treatment or the dietary lipid supplement. Sciatic nerve myo
      inositol content was unaltered while mannose, fructose, glucose, and sorbitol
      levels were elevated in the diabetic groups and these changes were independent of
      the cilazapril treatment or the dietary lipid supplement. These results indicate
      that in the rat, cilazapril treatment or dietary GLA, at the doses tested, are
      effective in preventing the deficit in the NCV induced by diabetes.

PMID- 9559485
TI  - Calcaneal fractures in diabetic patients.
AB  - We would like to present 23 calcaneal fractures in 22 patients of whom 21 had
      type I diabetes mellitus. There appear to be three basic fracture types: (1) a
      superiorly displaced extra-articular avulsion fracture of the posterior calcaneus
      (or Iowa fracture), which occurred in 12 patients (five men, seven women); (2) a
      mid-calcaneal compression fracture in six patients (four men, two women), and (3)
      a cleavage or "wedge" type fracture in four patients extending from the calcaneal
      tubercle (one man, 3 women). All four of this last group of patients had a
      history of a chronic penetrating ulcer, and this is noteworthy since only one
      other patient out of the remaining 18 in groups 1 and 2 had a similar history.
      Most patients had decreased bone mineralization: 15 patients were on long-term,
      high-dose steroids, and 18 patients had either poor renal function or complete
      renal failure (11 of 12). Fourteen patients had received either renal or pancreas
      transplants. Eight patients were on restricted weight bearing prior to their
      fractures. We believe that diabetic patients are more prone to calcaneal
      fractures than the general population, and early diagnosis is imperative,
      followed by early treatment to prevent significant bony deformity.

PMID- 9559484
TI  - Pregnancy does not induce or worsen retinal and peripheral nerve dysfunction in
      insulin-dependent diabetic women.
AB  - In order to verify whether pregnancy induces or worsens diabetic retinopathy or
      somatic and autonomic neuropathy, 16 insulin-dependent diabetic (IDDM) pregnant
      women, 14 age-matched nondiabetic pregnant women, and 12 IDDM nonpregnant women
      matched for age and disease duration were studied. Plasma glucose, HbA1c, and
      fructosamine were repeatedly assayed during pregnancy. Retinopathic and
      neuropathic endpoints were evaluated through ophthalmoscopy, electrophysiology of
      left peroneal and sural nerves (motor and sensory conduction velocities), and
      cardiovascular autonomic tests (deep breathing, cough test, lying-to-standing).
      In the IDDM pregnant women, evaluations were performed three times during
      pregnancy and 6 months after delivery. Good metabolic control was achieved during
      pregnancy. At baseline, nine IDDM pregnant women did not show signs of
      retinopathy, and seven had nonproliferative retinopathy. Only one patient showed
      worsening during pregnancy, but she improved after delivery. Motor conduction
      velocity, significantly lower in IDDM pregnant women, progressively improved,
      and, in the third trimester, was not significantly different from that of
      nondiabetic pregnant women. At baseline, none of the IDDM pregnant women had
      abnormal responses to cardiovascular autonomic tests. During pregnancy, the
      response to deep breathing appeared temporarily reduced in all pregnant women,
      possibly due to lowered ventilatory excursion at the end of pregnancy. In IDDM
      women with minimal or no retinopathy, and subclinical or no peripheral
      neuropathy, pregnancy does not appear to induce or worsen these complications.

PMID- 9559486
TI  - Low prevalence of long-term complications in non-insulin-dependent diabetes
      mellitus in France: a multicenter study. CODIAB-INSERM-ZENECA Pharma Study Group.
AB  - The aim of this study was to assess the prevalence of long-term complications in
      a large sample of French NIDDM patients. Therefore, 427 NIDDM patients 35-74
      years old were recruited in ten centers. Standardized clinical criteria and
      central reading for retinal and electrocardiographic changes were used to assess
      the presence of complications. The prevalence rates of complications were 29.7%
      and 3.3% for background and proliferative retinopathy; 21.8%, 6.1%, and 2.8% for
      microalbuminuria, proteinuria, and renal insufficiency; 19.9 and 11.7% for
      asymptomatic and symptomatic pheripheral neuropathy; 8.2% for orthostatic
      hypotension; 10.1% and 8.4% for angina pectoris and myocardial infarction; and
      13.1% and 6.3% for mild and moderate to severe peripheral vascular disease,
      respectively. In conclusion, prevalence rates in this study were lower than in
      most studies from other countries.

PMID- 9559487
TI  - Change in major amputation rate in a center dedicated to diabetic foot care
      during the 1980s: prognostic determinants for major amputation.
AB  - From 1990 to 1993, 115 diabetic patients were consecutively hospitalized in our
      diabetologic unit for foot ulcer and 27 (23.5%) major amputations were carried
      out. The major amputation rate of this series of cases was compared with that
      occurring in diabetic subjects taken into our hospital for foot ulcer in two
      previous periods: 1979-1981 (17 major amputations in 42 inpatients or 40.5%) and
      1986-1989 (26 major amputations in 78 inpatients or 33.3%). The comparison shows
      a progressive reduction in major amputation rate [Odds ratio 0.66, 95% confidence
      interval (CI) 0.46-0.96]. Univariate and multivariate analysis, carried out in
      the population of the 1990-1993 period, in order to detect the independent
      factors associated with major amputation show the following prognostic
      determinants of major amputation: Wagner grade (odds ratio 7.69, CI 1.58-37.53),
      prior stroke (odds ratio 35.05, CI 3.14-390.53), prior major amputation (odds
      ratio 3.49, CI 1.26-9.38), transcutaneous oxygen level (odds ratio 1.06, CI 1.01
      1.12), and ankle-brachial blood pressure index (odds ratio 4.35, CI 1.58-12.05),
      while an independent protective role was attributed to hyperbaric oxygen
      treatment (odds ratio 0.15, CI 0.03-0.64). In accordance with other studies, we,
      therefore, conclude that a comprehensive protocol as well as a multidisciplinary
      approach in a dedicated center can assure a decrease in major amputation rate.
      The parameters of limb perfusion were the modifiable prognostic determinants most
      strongly predictive for amputation.

PMID- 9559488
TI  - Morbidity in 565 type 2 diabetic patients according to stage of nephropathy.
AB  - Between 1988 and 1992, 565 type 2 diabetic patients were examined for nephropathy
      and diabetes-associated diseases during hospital treatment. Stages of nephropathy
      were defined as no clinical sign of nephropathy (N = 280), microalbuminuria (N =
      38), overt proteinuria (N = 105), impaired renal function (N = 55), and chronic
      dialysis therapy (N = 87). In dialyzed patients, HbA1c averaged 6.8%, and, in the
      other groups, HbA1c was between 7.6% and 8.3% (normal range, 3.8%-6.1%). Cataract
      was not associated with the severity of nephropathy. Stroke was most common in
      the stage of renal insufficiency (34%). The following complications, as found in
      medical history or as current event, showed a significant association with the
      stage of nephropathy and occurred most frequently in dialysis patients
      (percentage is displayed for patients with nephropathy in comparison to diabetic
      dialysis patients): hypertension (53%-89%), left ventricular hypertrophy (39%
      81%), myocardial infarction (14%-36%), peripheral vascular disease (27%-77%),
      foot lesions (7%-75%), minor or major amputations (3%-23%), proliferative
      retinopathy (6%-46%), blindness (2.9%-16.1%), and internal carotid artery
      stenosis (15%-36%). In this preselected cohort of diabetic patients, a high
      morbidity was found already without nephropathy that increased several-fold in
      the course of the development of nephropathy. Our data identify patients with
      diabetic nephropathy as a high-risk group for excess morbidity.

PMID- 9559490
TI  - Bolstering Sisyphus.

PMID- 9559489
TI  - Metformin: effects on cardiovascular risk factors in patients with non-insulin
      dependent diabetes mellitus.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) affects approximately 12 million
      people in the United States. NIDDM is frequently found to coexist with other
      conditions, such as obesity, dyslipidemia, atherosclerotic vascular disease, and
      hypertension, which contribute to morbidity and mortality. Although the major
      clinical objective in the management of NIDDM is to control hyperglycemia, the
      long-term objective is to prevent microvascular and macrovascular complications.
      Cardiovascular disease is the major cause of death in NIDDM patients. Although
      hyperglycemia may be adequately controlled, risk factors for coronary heart
      disease may remain unchanged. Treatment with metformin controls hyperglycemia and
      may have positive effects on cardiovascular risk factors. When used alone or in
      combination with sulfonylureas, metformin tends to stabilize or decrease weight,
      maintains or reduces insulin levels, has beneficial effects on plasma lipid
      profiles, and may also have beneficial effects on blood pressure and the
      fibrinolytic system.

PMID- 9559491
TI  - Late removal of releasable sutures after trabeculectomy or combined
      trabeculectomy with cataract extraction supplemented with antifibrotics.
AB  - PURPOSE: Releasable scleral flap sutures have been effectively used in
      trabeculectomy. The suggested time for suture removal is within the first two
      postoperative weeks. The authors wished to determine whether the use of
      intraoperative antifibrotics alters the time of suture removal and the results of
      surgery. METHODS: The charts of 324 patients (388 eyes) undergoing trabeculectomy
      and 141 patients (174 eyes) undergoing combined trabeculectomy with cataract
      extraction with a minimum follow-up of 12 months were retrospectively reviewed.
      All eyes received intraoperative antifibrotics; mitomycin C in 534 eyes and 5
      fluorouracil in 29 eyes. Two releasable scleral flap sutures were used in all of
      the eyes. RESULTS: The removal time of at least one of the two releasable sutures
      was later than 21 days postoperatively in 89 eyes of 83 patients with
      trabeculectomy (22.9%) and in 58 eyes of 55 patients with combined surgery
      (33.3%). The suture removal was deferred in 39 eyes because of an early
      complication such as hypotony (intraocular pressure (IOP) < or = 5 mm Hg), bleb
      leak, or shallow or flat anterior chamber. There was no complication in the other
      108 eyes, but suture removal was delayed until the IOP was more than 10 mm Hg.
      Immediate IOP reduction was (mean +/- standard deviation) 6.3 +/- 2.8 mm Hg when
      suture removal was performed beyond 3 weeks. There was a decreased response as
      the postoperative time until suture removal increases (r = -0.57). No serious
      complication associated with late suture removal was noted during the follow-up
      period (mean +/- standard deviation, 19.8 +/- 10.1 months). CONCLUSION:
      Intraoperative pharmacologic modulation of wound healing in trabeculectomy and
      combined trabeculectomy with cataract extraction extends the period that
      releasable suture removal is clinically effective. However the response decreases
      with a longer interval to releasable suture removal.

PMID- 9559492
TI  - Risk of hypotony after primary trabeculectomy with antifibrotic agents in a black
      west African population.
AB  - PURPOSE: To evaluate the risk of hypotony and hypotony maculopathy following
      trabeculectomy with 5-fluorouracil (5-FU) and mitomycin C (MMC) in a black West
      African population. METHODS: One hundred and one eyes of black Ghanaian patients
      with advanced primary open-angle glaucoma received intraoperative antifibrotic
      therapy with trabeculectomy as part of two randomized clinical trials. Overall,
      57 patients received 5-FU (50.0 mg/ml for 5 minutes) and 44 received MMC (0.5
      mg/ml for 3.5 minutes). All cases were performed by one of five surgeons at a
      single outpatient surgery center. RESULTS: Two of 101 eyes had a final
      intraocular pressure (IOP) of less than 5 mm Hg and were thus classified as
      having hypotony. No patient in either group was noted to develop hypotony-related
      maculopathy. Overall mean pre- and postoperative IOPs were 30.1 and 15.9 mm Hg,
      respectively. The patients receiving intraoperative MMC had a lower mean
      postoperative IOP (14.7 mm Hg) than those receiving 5-FU (first study, 17.1 mm
      Hg; second study, 16.7 mm Hg; p = 0.05). Mean overall follow-up was 17.7 months
      and did not differ significantly between the MMC and combined 5-FU groups.
      CONCLUSION: Hypotony following trabeculectomy supplemented with antifibrotic
      agents is a rare complication in this population. No eyes in either clinical
      trial developed hypotony maculopathy, suggesting that the prevalence of this
      condition is substantially lower in black West Africans than in whites.

PMID- 9559493
TI  - Molteno implant with mitomycin C: intermediate-term results.
AB  - PURPOSE: The authors examine the intermediate-term effects of adjunctive
      intraoperative mitomycin C (MMC) in a cohort of patients who received double
      plate Molteno implants for complicated glaucomas. METHODS: A consecutive series
      of 21 patients who received MMC 0.5 mg/ml for 5 minutes as an adjunct to a double
      plate Molteno implant was compared by life-table analysis to a historical control
      group of 18 patients who received either no adjunct or 5-fluorouracil (5-FU) but
      no MMC. RESULTS: At three years follow-up, 35% (95% confidence interval (CI), 15
      57%) of patients who received MMC avoided failure criteria of intraocular
      pressure (IOP) less than 6 mm Hg or more than 21 mm Hg, addition of glaucoma
      medication, reoperation for glaucoma, or tube removal. Seventeen percent (95% CI,
      4-37%) of patients in the control group at three years follow-up met similar
      criteria (p = 0.039). No late complications of tube erosion were seen in the MMC
      group. CONCLUSION: Intraoperative MMC offers an increased likelihood of a two- to
      three-year period of medication-free IOP control in patients undergoing double
      plate Molteno implants, compared to similar patients receiving 5-FU or no
      adjunctive antimetabolite therapy.

PMID- 9559494
TI  - The use of the consensual light reflex as an aid to performing laser peripheral
      iridectomy in patients with pigment dispersion syndrome and pigmentary glaucoma.
AB  - PURPOSE: The authors explore an alternative method of performing laser peripheral
      iridectomy (LPI) in patients with pigment dispersion syndrome and pigmentary
      glaucoma (PDS/PG) who are high myopes and therefore at increased risk of
      developing retinal detachment. METHODS: Four myopic patients with PDS/PG had LPI
      performed in one eye. A transilluminator was held up to the opposite eye to
      provide pupillary constriction via the consensual light reflex. No miotics were
      used. RESULTS: All LPIs were easily performed without complications. CONCLUSION:
      The authors present an alternative method to the standard use of pilocarpine for
      LPI theoretically to decrease further the incidence of retinal detachment in
      populations predisposed to it.

PMID- 9559495
TI  - Costs of treating primary open-angle glaucoma and ocular hypertension: a
      retrospective, observational two-year chart review of newly diagnosed patients in
      Sweden and the United States.
AB  - PURPOSE: The objective of this study was to investigate what treatment strategies
      prevail in different countries for patients newly diagnosed with primary open
      angle glaucoma (POAG) or ocular hypertension (OH) only and initiated on treatment
      with beta-blockers, and to estimate the total direct cost of treatment for two
      years. In addition, differences in costs between and within the countries and the
      determinants of variations in costs across patients were examined. MATERIALS AND
      METHODS: The authors performed a retrospective medical record analysis in several
      academic and office-based study centers in Sweden and the United States. Standard
      costs for each resource item were determined and applied to all centers within
      the country. Differences in treatment costs within the countries are thus the
      effect of differences in treatment strategies, not of differences in prices.
      RESULTS: There was considerable variation between the centers of each country.
      Sweden had a higher number of surgical interventions, which may be explained by
      the fact that the Swedish cohort had a higher mean intraocular pressure (IOP) at
      baseline and a higher proportion of patients with definite POAG and exfoliation
      glaucoma. However, in both countries the mean IOP at study end was approximately
      18 mm Hg. Total direct costs for two years were 15,119 SEK (US$2,160; $1US = 7
      SEK) and $2,109, respectively. In a multiple regression analysis, the estimated
      effects of baseline IOP and of IOP change after treatment initiation on treatment
      costs were positively and negatively significant, respectively, in both
      countries. CONCLUSION: Despite differences in baseline diagnosis and in treatment
      strategies, mean IOP was decreased to 18 mm Hg in both countries. Baseline IOP
      was positively correlated with treatment costs, while the initial IOP-lowering
      effect of treatment was negatively correlated with two-year costs.

PMID- 9559496
TI  - Cold pressor test and plasma endothelin-1 concentration in primary open-angle and
      capsular glaucoma.
AB  - PURPOSE: The authors investigate cutaneous capillary blood flow using the cold
      pressor test and plasma endothelin-1 (ET-1) concentration in primary open-angle
      glaucoma (POAG) and capsular glaucoma (CG), and evaluate the connection between
      the two factors, which reflect vasoconstrictive mechanisms with a potential role
      in the pathogenesis of glaucoma. METHODS: The ET-1 concentration of venous blood
      plasma samples from 20 patients with POAG, 22 patients with CG, and 44 healthy
      volunteers was measured using a radioimmunoassay kit. On a separate occasion, the
      right hand was subjected to the cold pressor test (hand immersed in 4 degrees C
      water for 30 seconds, then in 30 degrees C water for 2 minutes), during which
      cutaneous capillary blood flow of the left middle finger was measured using a
      Periflux 4001 Master Laser Doppler Flowmeter (Perimed AB, Jarfalla, Sweden).
      RESULTS: In the CG group, baseline cutaneous capillary blood flow was
      significantly lower than either that of POAG (p = 0.001) or that of the healthy
      group (p = 0.046). In the CG group, time to maximal cold-induced flow reduction
      was significantly longer than in the POAG group (p = 0.028) or in the healthy
      group (p = 0.025). Also, recovery time was significantly longer in CG than in the
      healthy group (p = 0.008) and tended to be longer than in the POAG group. No
      statistically significant difference between the groups was found either in the
      frequency of increased vasospastic response (cold-induced flow reduction higher
      than 70% of the baseline value) or in ET-1 concentration. No correlation was seen
      between ET-1 concentration and the findings of the cold pressor test. CONCLUSION:
      The results suggest that in CG, which is a systemic disease with vascular
      abnormalities, baseline cutaneous capillary perfusion and its response to cold
      and warmth are altered, without any alteration of plasma ET-1 level. The authors
      found that both plasma ET-1 level and the response to the cold pressor test are
      normal in patients with POAG. These findings suggest that regulation of cutaneous
      capillary perfusion and the concentration of plasma ET-1 are not related to each
      other in patients with glaucoma.

PMID- 9559497
TI  - Comparison between high-pass resolution perimetry and differential light
      sensitivity perimetry in patients with glaucoma.
AB  - PURPOSE: High-pass resolution perimeters such as the Ophthimus (High Tech Vision,
      Malmo, Sweden) may provide an easier, faster assessment of the visual field than
      conventional perimeters such as the Humphrey (Humphrey Instruments Inc., San
      Leandro, CA, U.S.A.), which is based on differential light sensitivity. The
      Ophthimus provides global indices and statistical analyses conceptually similar
      to those produced by the Humphrey. In addition, the Ophthimus provides, as a
      unique parameter, the estimated neural capacity. PATIENTS AND METHODS: Twenty-one
      patients with chronic open-angle glaucoma and reliable fields on both Humphrey
      and Ophthimus testing were evaluated. The results from the two different
      techniques were compared. RESULTS: The estimated neural capacity was correlated
      to global deviation and mean deviation at a statistically significant level.
      There were also correlations between mean deviation and global deviation and
      between pattern standard deviation and local deviation, but not between retest
      standard deviation and short-term fluctuation. CONCLUSION: It is not clear at
      this point if the neural capacity of the Ophthimus provides any clinically useful
      information over and above global deviation. Mean test time was shorter with the
      Ophthimus system than the Humphrey. Performance on the reliability indices was
      better for the Ophthimus. The Ophthimus may prove useful in following patients
      with glaucoma.

PMID- 9559498
TI  - Incidence of elevation of intraocular pressure over time and associated factors
      in normal-tension glaucoma.
AB  - PURPOSE: The authors determine whether intraocular pressure (IOP) increases to
      levels that challenge the diagnosis of normal-tension glaucoma (NTG) and
      determine clinical factors associated with the IOP elevation. METHODS: Forty
      patients with NTG who met the following enrollment criteria were selected: IOPs
      less than 21 mm Hg during initial 24-hour pressure curve and throughout the
      subsequent 12 months; examined every 1 to 4 months for at least 4 years; and no
      ocular hypotensive treatment. The eye with the higher mean IOP during the initial
      24-hour pressure curve was selected from each patient. The observation period
      ranged from 4.0 years to 7.8 years (mean, 5.2 years). Significant IOP elevation
      was defined as a significant increase (p < 0.05) of IOP over time, determined by
      Spearman rank correlation coefficient method. The IOP elevation was correlated to
      clinical factors by means of a logistic multiple regression analysis (LOGIST
      procedure using PC-SAS, SAS Institute, Inc. Cary, NC, U.S.A.). RESULTS: Eleven
      eyes were rated positive for IOP elevation. The regression model demonstrated
      that maximum IOP during the initial 24-hour pressure curve and the development of
      disc hemorrhage (DH) were significantly correlated with IOP elevation (p = 0.006
      and p = 0.049, respectively). The odds ratios calculated were 1.98 per 1 mm Hg
      rise of maximum IOP during the initial 24-hour pressure curve and 6.54 for
      positive DH. CONCLUSIONS: Intraocular pressure might increase in NTG eyes
      following the initial diagnosis. A higher maximum IOP during initial 24-hour
      pressure curve and the development of DH during follow-up was significantly
      associated with subsequent IOP elevation in NTG patients.

PMID- 9559500
TI  - Diurnal intraocular pressure curves in healthy rhesus macaques (Macaca mulatta)
      and rhesus macaques with normotensive and hypertensive primary open-angle
      glaucoma.
AB  - PURPOSE: The authors identify any diurnal intraocular pressure (IOP) variation in
      healthy Cayo Santiago macaques, as well as Cayo Santiago macaques with
      normotensive and hypertensive primary open-angle glaucoma (POAG), to further
      evaluate their potential value as a model for human POAG. METHODS: Twenty-four
      monkeys (eight animals each of the healthy control, normotensive glaucoma, and
      hypertensive glaucoma groups) were sedated with ketamine hydrochloride and the
      IOP measured hourly from 8:00 AM until 3:00 PM with a Tonopen XL applanation
      tonometer (Mentor, Norwell, MA, U.S.A.). Mean IOP time profiles, mean IOPs at
      each observation time, and linear trends in mean IOP over time were compared
      among groups. Intraocular pressure rate-of-change over time and residual
      variation about the regression line for each individual eye were analyzed.
      Cup/disc ratio (C/D) was compared with baseline IOP, IOP profile mean and slope,
      and IOP residual variation. RESULTS: A significant group and time effect on mean
      IOP (p = 0.0001 and 0.011, respectively), with highest values at 2:00 PM or 3:00
      PM, and a significant increasing linear trend in mean IOP over time in the
      hypertensive group were observed (p = 0.012). Intermediate readings between
      control and hypertensive mean IOPs were identified for the normotensive glaucoma
      group. The biggest range of IOP variation was found in the hypertensive glaucoma
      monkeys. Higher variations in IOP did not lead to an increase in C/D.
      CONCLUSIONS: This study provides evidence that the Cayo Santiago macaques are a
      valuable model for human normotensive and hypertensive POAG.

PMID- 9559499
TI  - Detection of early glaucomatous structural damage with confocal scanning laser
      tomography.
AB  - PURPOSE: The authors determine which optic disc topographic parameters obtained
      by the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg,
      Germany) are most useful in detecting individuals with early glaucomatous visual
      field loss. METHODS: Ninety-nine eyes of 49 healthy individuals and 50 age
      matched individuals with early glaucomatous visual field loss were included.
      Three images were obtained and the mean topography image was created and used in
      the analyses. The HRT discriminant analysis function (software version 2.01) was
      applied and compared to the Fisher linear discriminant function developed in this
      population. Analysis was repeated after stratifying by disc area (< 2 mm2 or 2-3
      mm2). RESULTS: There were statistically significant differences between the
      healthy and glaucomatous groups for all optic disc topographic parameters (p <
      0.05) measured. These differences remained after the analysis was repeated
      controlling for disc size, except for height variation contour. Applying the HRT
      discriminant function to this study population resulted in sensitivity and
      specificity of 62% and 94%, respectively. The sensitivity was 83% while
      specificity remained high (91%) for larger disc sizes. Using this data,
      additional discriminant functions that differentiated similarly between the two
      groups were found. The best formula used cup-shape measure (third moment), rim
      area, height variation contour, and retinal nerve fiber layer thickness and had a
      sensitivity and specificity of 78% and 88%, respectively. CONCLUSIONS: Several
      different discriminant analysis formulas are capable of detecting early
      glaucomatous visual field loss in a comparable manner. The characteristics of the
      study population are likely to influence the discriminating power of these
      various formulas.

PMID- 9559501
TI  - Bleb-related ocular infection.

PMID- 9559502
TI  - Initial treatment of exfoliative glaucoma.

PMID- 9559503
TI  - Circadian rhythm of intraocular pressure.
AB  - Although it is well known that intraocular pressure (IOP) in humans varies
      throughout day and night, no consistent circadian pattern has been established.
      In laboratory rabbits, however, a consistent circadian rhythm of IOP has been
      confirmed and further characterized in recent years. The current knowledge about
      the nocturnal IOP elevation in rabbits is reviewed and the implications for the
      study of human circadian IOP pattern is discussed.

PMID- 9559504
TI  - Managing orbital cellulitis.

PMID- 9559505
TI  - Clinical practice guidelines for the management of orbital cellulitis.
AB  - PURPOSE: A retrospective study was performed to review the management of
      periorbital and orbital cellulitis at Miami Children's Hospital, between January
      1, 1993 and February 15, 1996. RESULTS: One hundred and one patients were
      included in this study. The variables analyzed in this study included age, sex,
      length of hospital stay, imaging studies, laboratory tests, and microbiology
      specimens collected. Patients were classified according to the modified Chandler
      classification. Average length of stay for our patient population was 4.5 days.
      Data regarding the radiologic studies, laboratory tests, and microbiology yield
      of specimens were analyzed. CONCLUSIONS: The incidence of orbital infection,
      manifested by lid swelling alone is much more common (stages I and II) than
      orbital infection involving postseptal findings (stages III, IV, and V); 84.16%
      compared with 15.84%, respectively. An updated approach and a general guideline
      for the management of periorbital and orbital cellulitis according to the
      clinical staging of the process is presented.

PMID- 9559506
TI  - Can congenital nasolacrimal-duct obstruction interfere with visual development? A
      cohort case control study.
AB  - PURPOSE: To ascertain if tear film disturbance in congenital nasolacrimal-duct
      obstruction (CNLDO) interferes with visual maturation. METHODS: Review of a
      cohort of children in which the occurrence and duration of CNLDO had been
      previously documented. Information obtained included acuity, refractive data, and
      presence or absence of strabismus. The incidence of abnormality in the CNLDO
      group was compared with that in controls, which were fellow eyes in those
      children with unilateral obstruction, and all children with no history of CNLDO.
      RESULTS: Of 4792 children, visual acuity data were obtained on 2249. There was no
      difference in the incidence of amblyopia in CNLDO children compared with controls
      (p < 0.89) nor in the watering eye compared with the fellow eye (p < 0.58). No
      correlation between refractive error or astigmatism and CNLDO (p < 0.26 and p <
      0.32 respectively) was found. Strabismus was no more common in CNLDO than in
      controls (p < 0.89). CONCLUSIONS: This study found no evidence to suggest that
      visual maturation is adversely affected by allowing spontaneous resolution of
      CNLDO.

PMID- 9559507
TI  - The accommodative convergence/accommodation (AC/A) and near convergence/distance
      (NC/D) ratios in esotropia.
AB  - INTRODUCTION: In esotropias, measurement of AC/A and NC/D ratios are important
      for exact classification and adequate therapy. We devised a table for the
      calculation of AC/A and NC/D ratios to facilitate their estimation. METHOD: For
      the assessment of AC/A ratio, we used the gradient method range 6 Dsph and for
      the NC/D ratio we used the heterophoria method. For the calculation of both
      ratios, we used our own table. A series of 102 children were examined. RESULTS:
      The mean value of AC/A ratio for esotropias was 4.86 +/- 2.05. The mean value of
      AC/A ratio for the control group was 3.9 +/- 1.92. The difference was 0.96 and
      was statistically significant at the level of 5% (Student's t test). The AC/A
      ratio is high in esotropia ranging from 1 to 10. At 58% of esotropias, the AC/A
      ratio is higher than the mean value of AC/A ratio of the control group. The mean
      value of the NC/D ratio for esotropia was 5.9 +/- 1.51. The mean value of the
      NC/D ratio for the control group was 5.1 +/- 1.5. The difference of 0.8 was
      statistically significant at a level of 5%. Thus, in esotropia the NC/D ratio is
      high. The NC/D ratio in esotropia ranges from 1 to 10. The NC/D ratio is low in
      16% of esotropias. CONCLUSION: Our own table for calculating the AC/A and NC/D
      ratios was useful because it facilitates their determination. The mean values of
      AC/A and NC/D ratios in esotropia are high and range from 1 to 10. In 58% of
      cases the AC/A ratio is high and in 84% of cases the NC/D ratio is high and can
      be responsible for the oculomotor imbalance.

PMID- 9559508
TI  - Lenz syndrome in two sisters: clinicopathologic correlations of the ocular
      anomalies.
AB  - BACKGROUND: The Lenz syndrome (Mendelian inheritance in Man catalog number
      309,800) is a presumed X-linked recessive disorder. Major diagnostic criteria
      include ocular, skeletal, and urogenital manifestations. We describe two sisters
      and the two sons of one of them with Lenz syndrome. The eye from one boy was
      removed because of pain and total loss of vision, allowing histopathologic
      documentation of the ocular malformations. METHODS: Clinicopathologic case
      report. RESULTS: Two sisters in this family displayed several of the major
      diagnostic criteria of the Lenz syndrome. The stunted growth of the eye, and the
      ocular and non-ocular anomalies defines the microphthalmos as monogenic, complex,
      and colobomatous. CONCLUSION: The pattern of inheritance of Lenz syndrome is best
      explained by X-linked dominant transmission. Future reports of familial cases
      with an excess of affected females are needed to confirm this hypothesis.

PMID- 9559509
TI  - CHARGE association: histopathological report of two cases and a review.
AB  - BACKGROUND: The CHARGE association (C = coloboma, H = heart disease, A = atresia
      or stenosis of the choanae, R = retarded growth and development or CNS anomalies,
      G = genital hypoplasia, and E = ear anomalies or deafness) is a rare, recently
      well-recognized clinical study. The ophthalmic abnormalities have been described
      in numerous reports, but the ocular histopathologic findings have not been
      presented in detail. METHODS: We conducted gross and microscopic studies of eyes
      of two patients with the CHARGE association obtained postmortem. RESULTS: The
      eyes in one case had a small, symmetrical, inferior nasal coloboma of the
      choroid. In the other case, extensive inferior nasal colobomas of the iris,
      ciliary body, and choroid with retinal dysplasia, ectopic retinal/glial tissue in
      the sclera and hypoplasia of the optic nerve head were present. CONCLUSION: We
      document the histopathological features of eyes of two subjects with the CHARGE
      association. The abnormalities of these eyes were typical ocular colobomas
      presumably resulting from the failure of complete closure of the optic fissure.

PMID- 9559510
TI  - Evaluation of a hand-held autorefractor in children younger than 6.
AB  - PURPOSE: To evaluate a hand-held portable autorefractor in a pediatric population
      and compare results with those found on retinoscopy by experienced pediatric
      retinoscopists. METHODS: One-hundred and two children aged 5 to 72 months were
      examined with and without cycloplegia using an autorefractor, and the results
      compared with those found on standard retinoscopy by two ophthalmologists masked
      as to the autorefractor findings. Results were converted from conventional
      notation using plus cylinder to the h-space notation and compared in three
      dimensional h-space. RESULTS: There was remarkable agreement between the results
      found by autorefraction and manual retinoscopy using loose lenses or a phoropter.
      The findings were similar both for sphere and cylinder across the age ranges
      studied. CONCLUSIONS: The Nikon Retinomax is an accurate instrument to estimate
      refractive error in children younger than 6 and could prove useful in the office,
      the operating room, or as a screening device.

PMID- 9559511
TI  - Bilateral Peter's anomaly in an infant with 49,XXXXY syndrome.

PMID- 9559512
TI  - Prominent ocular findings as an early manifestation of systemic lupus
      erythematosus.

PMID- 9559513
TI  - Acquired combined hamartoma of the retina and pigment epithelium following
      parainfectious meningoencephalitis with optic neuritis.

PMID- 9559514
TI  - Panuveitis associated with rifabutin prophylaxis in a pediatric HIV-positive
      patient.

PMID- 9559515
TI  - An XX male with microphthalmos and sclerocornea.

PMID- 9559516
TI  - Congenital microcoria: case report and histological study.

PMID- 9559517
TI  - [Epidemiologic markers of Salmonella].
AB  - Salmonellae are enterobacteria responsible for outbreaks of human and animal
      clinical diseases, with important hygienic and economic consequences. Accurate
      epidemiological studies require the use of efficient markers, which make it
      possible to trace the establishment and diffusion of different bacterial strains
      and also to evaluate the similarities between different isolates. Numerous
      phenotypic and genotypic markers applicable to Salmonella are available for these
      epidemiological studies. Nevertheless, the relative interest of those markers
      depends on the serotypes, and a different hierarchy can be achieved for the
      Typhimurium and Enteritidis serotypes.

PMID- 9559518
TI  - Comparative efficacy of different insecticides in the treatment of cattle
      hypodermosis in north-eastern Algeria.
AB  - The efficacy of different drugs (microdose of ivermectin, doramectin and
      moxidectin at the recommended doses and topically applied rotenone) against the
      first, second and third instar larvae of Hypoderma bovis and H. lineatum was
      studied in cattle in the El Tarf area (northeastern Algeria). Before performing
      the efficacy trials, the life cycle of the warble fly was studied at the
      slaughterhouse between July 1993 and June 1994. This survey revealed that both
      species of warble fly were present in this area: L1 larvae of H. lineatum were
      found around the oesophagus between August and January, whereas L1 larvae of H.
      bovis were observed around the spine from November until March. Warbles were
      present under the skin from the end of October until May. The nymphal phase took
      place between February and May. As a result of this study the authors recommend
      applying chemoprophylaxis (treatment against L1) in September. This work also
      confirmed the excellent efficacy of avermectins and milbemycins against the three
      instar larvae of Hypoderma sp. under the field conditions prevailing in Algeria.
      Rotenone has a lower efficacy (95%) which is limited to the second and third
      instar larvae. However, this drug appears useful in dairy cattle.

PMID- 9559519
TI  - Relationship between individual-cow udder health status in early lactation and
      dairy cow characteristics in Brittany, France.
AB  - Data from a 4-year ecopathological survey involving 47 dairy farms in Brittany
      (France) were used to determine the individual animal characteristics associated
      with the udder health profiles of clinical and subclinical mastitis, and the
      presence of minor or major pathogens in milk during early lactation. Herd effect
      was taken into account and a within-herd analysis using factorial correspondence
      analysis and a decomposition of chi-square distance was performed. In primiparous
      cows, the main association observed was between milk production and intramammary
      infections with major pathogens. The dirtiness score showed contradictory
      relationships with udder health profiles. The indoor/outdoor transition period
      was unfavourable for udder health status; since the frequency rate of subclinical
      and clinical mastitis increased during this period. In multiparous cows,
      intramammary infections by minor or major pathogens were closely associated with
      non-infectious udder diseases, but the main effect was due to parity. Old cows
      were generally affected by higher somatic cell counts than younger cows
      regardless of whether the SCC were associated with clinical mastitis or not.

PMID- 9559520
TI  - In vivo studies on lysosubtilin. 2. Efficacy for treatment of post-partum
      endometritis in cows.
AB  - Lysosubtilin is a broad-spectrum preparation of lytic enzymes from Bacillus
      subtilis designed for veterinary medicine. This study demonstrates its efficacy
      for the treatment of post-partum endometritis in cows. Prior to the determination
      of optimal therapeutic doses, samples taken from the uterus of sick animals were
      examined microbiologically. The examinations revealed a high incidence of
      polymicrobial infections (65.0%) caused by various mixtures of bacteria (both
      Gram-positive and Gram-negative) and fungi/yeasts. Dose-determination studies
      involved 160 cows with clinical signs of post-partum endometritis. For treatment
      both aqueous and oil-based formulations were tested and the optimal dose was
      found to be 2 x 10(6) U lysosubtilin dissolved in 100 mL of distilled water. When
      administered intrauterinarily twice a week until recovery this dose resulted in a
      100% clinical recovery rate (versus 90%) and a statistically significant decrease
      (73 +/- 5 d), when compared with cows treated with neofur (92 +/- 9 d, P < 0.05)
      in the calving-to-conception interval. These findings were confirmed by results
      of field trials performed in four Former Soviet Union republics (Byelarus,
      Estonia, Lithuania, Russia) on 932 cows. Increases in clinical recovery (93.7
      versus 80.2%, P < 0.05) and conception rates (64.4 versus 45.8%, P < 0.01) were
      found to be statistically significant when compared with cows treated with neofur
      or uterosan. We therefore conclude that lytic enzyme preparations are prospective
      antimicrobial drugs and when used to combat animal diseases they may serve as a
      possible alternative to common antibiotics.

PMID- 9559521
TI  - Small intestinal motility disorders in preruminant calves chronically fed a diet
      based on antigenic soya: characterization and possible mediators.
AB  - Intestinal motility disorders and some mediators implicated in these disorders
      were studied in preruminant calves that had been chronically fed a diet
      containing an antigenic heated soyabean flour (HSF) for 3 months. The calves in
      the present study had previously been shown to present strong immune reactions
      against soyabean proteins, as assessed through plasma antibody titres, direct
      skin tests and in vitro lymphoproliferation. Four of these calves sensitive to
      soya were fitted with an abomasal catheter and wire electrodes on the jejunum.
      Myoelectric activity was recorded over 7 h following test meals containing skim
      milk powder (SMP), HSF or a non-antigenic hydrolysed soya protein isolate (HSPI).
      The pattern of myoelectric complexes migrating to the jejunum was regular with
      SMP (mean durations of phases I, II and III: 26, 38 and 5.28 min, respectively).
      With HSF, diarrhoea appeared, and the total duration of phase I decreased from
      149 to 68 min (P < 0.01) while that of phase II increased from 239 to 328 min (P
      < 0.01). The mean duration of phase III decreased from 5.3 to 3.9 min (P < 0.01).
      These changes, including diarrhoea, were substantially reversed by feeding HSPI.
      When promethazine, a H-1 histamine receptor antagonist, was administered i.v.
      prior to feeding HSF the number of phases I tended to decrease and diarrhoea
      virtually disappeared. In contrast, indomethacin, a cyclooxygenase inhibitor, had
      limited effects on motility patterns and diarrhoea. These disorders were
      partially reproduced by i.p. administration of platelet-activating factor (PAF)
      prior to feeding with SMP. These findings suggest that calves chronically fed
      antigenic soya suffer from immune-mediated motility disorders which are linked to
      histamine action via H-1 receptors, and possibly with PAF. The role of
      arachidonic acid catabolites of the cyclooxygenase pathway is probably minor.

PMID- 9559522
TI  - Quantification of C5a/C5a(desArg) in bovine plasma, serum and milk.
AB  - Complement activation generates two potent inflammatory mediators from C5, C5a
      and its derivative C5a(desArg), which results from the removal of the C-terminal
      arginine by ubiquitous carboxypeptidases. In this paper we describe the
      purification of milligram amounts of bovine C5a(desArg) by a simplified
      procedure, and the preparation of mouse monoclonal antibodies (MAbs) to
      C5a/C5a(desArg) which do not recognize native C5. A MAb was used to develop a
      sandwich ELISA which made it possible to quantify levels of C5a/C5adesArg in
      bovine biological fluids. Small amounts (means +/- SEM) of C5a/C5a(desArg) were
      found in EDTA-plasma (0.58 +/- 0.06 ng.mL-1). The anticoagulant EDTA was more
      efficient than citrate or heparin in inhibiting in vitro activation of the
      complement system. Complement activation occurred during coagulation since the
      baseline concentration of C5a/C5a(desArg) (15.4 +/- 4.1 ng.mL-1) was higher than
      in plasma. Zymosan, a potent activator of the complement cascade, was used to
      generate C5a/C5a(desArg). The time-course of the reaction and the dose-effect of
      zymosan were investigated. Optimal conditions were incubation at 39 degrees C for
      1 or 2 h with 2 mg of zymosan per mL of serum. The maximal concentration of
      C5a/C5a desArg attained in zymosan-activated serum was 4.28 +/- 0.14
      micrograms.mL-1. Normal milk (from healthy, uninflamed mammary glands) contained
      on average 0.12 ng of C5a/C5a(desArg).mL-1 (range 0.02-0.19 ng.mL-1). The maximal
      amount of C5a/C5a(desArg) which was generated in milk with zymosan was 1.1 ng.mL
      1 (range 0.68-2.17 ng.mL-1). In milk from quarters with subclinical infections by
      coagulase-negative staphylococci, values were 0.18 ng.mL-1 and 2.37 ng.mL-1 for
      spontaneous and zymosan-generated C5a/C5a(desArg) concentrations, respectively.
      In milk from Escherichia coli endotoxin-induced mastitis, C5a/C5a(desArg)
      concentrations (means of four cows) before and after zymosan activation reached
      6.5 ng.mL-1 and 55 ng.mL-1, respectively. These results indicate that a C5
      convertase can operate in normal milk, that only minute amounts of
      C5a/C5a(desArg) can be generated (less than 1/1,000 of plasma potential), but
      that much higher concentrations are reached in milk during endotoxin-induced
      inflammation. The ELISA made it possible to determine normal ranges of
      C5a/C5a(desArg) in bovine blood plasma and in milk, and is a valuable tool to
      define the variations of its concentrations in exudates during inflammatory
      reactions.

PMID- 9559523
TI  - Combined effect of ampicillin, colistin and dexamethasone administered
      intramuscularly to dairy cows on the clinico-pathological course of E. coli
      endotoxin mastitis.
AB  - The effects of a single intramuscular injection of a drug product containing
      ampicillin, colistin and dexamethasone, as a suspension in a diester of propylene
      glycol of medium-chain fatty acids, on the clinico-pathological course of
      experimental Escherichia coli-endotoxin mastitis was examined in 30 dairy cows.
      Cows were divided into five groups, six cows per group, and 24 of them were
      infused with E. coli endotoxin into two quarters of their udders. The drug
      product was injected at 25,000 IU colistin sulphate, 10.0 mg ampicillin anhydrate
      and 0.025 mg dexamethasone acetate.kg-1 body weight as follows: Group 2 cows,
      immediately post-endotoxin infusion (PEI); Group 3 cows, 2 h PEI and, Group 4
      cows, 4 h PEI. Group 1 cows were not treated with the product and served as a
      positive (endotoxin only) control while Group 5 cows were not challenged with
      endotoxin and were not treated with the product. A clinical mastitis score (CMS)
      was developed to quantitatively assess the degree of inflammation. Blood
      biochemistry and hematological parameters were used to monitor the immediate
      effects of treatment on several conventional inflammatory markers. Milk somatic
      cell counts (MSCC), milk electrical conductivity and daily milk production were
      among the parameters used to monitor systemic and local inflammatory reactions.
      Administration of the drug product immediately PEI and 2 h PEI clearly nullified
      some of the most severe early systemic reactions to inflammation but the effect
      of therapy on the local inflammatory markers was not as obvious. Notewhorthy,
      however, were the effects of the treatment on reducing the duration of elevated
      quarter MSCC and the increase in the speed of return to pre-endotoxin challenge
      daily milk production levels.

PMID- 9559524
TI  - Micropuncture study on urea movements in the kidney cortical tubules of low
      protein fed sheep.
AB  - Micropuncture studies of late proximal, early and late distal cortical tubules
      were carried out on kidneys of normal (NP) and low (LP) protein fed sheep in
      order to investigate the participation of these segments in the urea sparing
      induced by protein restriction in the diet. A low protein diet induced
      significant reductions in the fractional (-54%) and total (-84%) urea excretion,
      revealing an enhanced capacity for urea conservation. Micropuncture data did not
      show any difference in the proximal tubule functions between both groups of
      sheep. In distal cortical tubules the fractional delivery of urea (early distal,
      0.61 +/- 0.06 for NP and 0.77 +/- 0.06 for LP sheep, not significant (NS); late
      distal, 0.45 +/- 0.07 for NP and 0.71 +/- 0.09 for LP sheep, P < 0.05) showed a
      relatively larger amount of urea present in the late distal tubule of protein
      restricted sheep. The tubular fluid-to-plasma inulin ratio in the late distal
      tubule was found to be lower in LP sheep (4.33 +/- 0.23 versus 8.58 +/- 0.9 in NP
      sheep, P < 0.01). The tubular flow rate, reduced in the early distal tubules of
      LP sheep (10.87 +/- 0.99 versus 18.92 +/- 2.58 nL.min-1 in NP sheep, P < 0.05),
      was not different in the late distal tubules from values in normally fed animals
      (6.65 +/- 0.90 versus 7.73 +/- 0.94 nL.min-1 in NP sheep, NS). These findings
      suggest a decreased distal water reabsorption coincident with the relatively
      larger amounts of intraluminal urea in LP sheep. This relatively larger urea
      delivery to the initial collecting duct could increase the subsequent urea
      reabsorption in protein restricted sheep.

PMID- 9559526
TI  - [Viral hepatitis G (HGV)].

PMID- 9559525
TI  - Purification of a leucine aminopeptidase from Eimeria falciformis.
AB  - A leucine aminopeptidase was purified from the oocysts of Eimeria falciformis
      using affinity chromatography and gel filtration techniques. It had a molecular
      weight of 45-50 kDa. Its maximal activity against leucyl-p-nitro anilide was at
      pH 8.6. It is a metallo-enzyme highly inhibited by bestatin.

PMID- 9559527
TI  - [Immunoadjuvant and antiviral properties of saponins].

PMID- 9559528
TI  - [Circulation of viruses of the California serocomplex (Bunyaviridae, Bunyavirus)
      in the central and southern parts of the Russian plain].
AB  - Seventy strains of California group viruses were isolated in the Central and
      Southern territories of the Russian plain situated in the Southern taiga, mixed
      forest, broad-leaved forest, forest-steppe, steppe, and semiarid zones. Sixty
      three of these were isolated from 873,300 mosquitoes, 4 from patients, and 3 from
      rodents. 57.1% of strains were isolated from Aedes communis and the associated
      species, 28.5% from Aedes excrucians and associated species, and rarely from
      other mosquito species. The mosquito infection rate was the highest in the
      Southern taiga zone: 0.0103%, this value decreasing towards the Southern areas.
      Out of 70 isolated strains 42.3% were identified as the Inkoo virus, 47.2% wer
      ejust referred to the California group, and only 2.8% were Tahyna and snowshoe
      hare viruses. The findings of serological screening of the population correlate
      with the results of virological studies of mosquitoes. Population morbidity is
      mainly caused by the Inkoo virus in the Southern taiga and mixed and broad-leaved
      forest, by Inkoo and Tahyna viruses in the steppe and forest-steppe zones, and by
      Tahyna virus in semiarid zone.

PMID- 9559529
TI  - [Diseases associated with viruses of the California encephalitis serogroup, in
      Russia].
AB  - Studies of 1986-1995 revealed diseases etiologically connected with California
      serogroup viruses (Bunyaviridae, Bunyavirus) all over the country. Highly endemic
      zones are the tundra, taiga, and leafy forest. The disease occurs mainly in
      summer, the patients are mostly young: under 30 years of age. Analysis of 183
      cases confirmed by laboratory findings enabled us to distinguish the following
      forms: influenza-like (70.9%) with the predominant involvement of the
      bronchopulmonary system (bronchitis and pneumonia) and neuroinfection (20.2%)
      (serous meningitis and meningoencephalitis).

PMID- 9559530
TI  - [A mechanism for limiting reproduction influenza A virus reassortants with
      incomplete functional compatibility of hemagglutinin and neuraminidase gene
      products].
AB  - The mechanism of decrease in the level of virus accumulation in reassortants with
      hemagglutinin (HA) and neuraminidase (NA) genes from different parents is
      studied. The reassortant viruses and their passage variants do not differ by the
      rate of virus protein production or their stability in infected cells. Electron
      microscopy and titration of infectious virus in culture fluid and cell-associated
      virus showed that the variants selected by serial passages accumulated mainly in
      the culture fluid, whereas the initial reassortant virions were predominantly
      cell-associated. These data suggest that incomplete removal of sialic acid
      residues by viral neuraminidase N1 in some reassortants results in re-attachment
      of virions to the infected cells and thus impairs the virus dissemination, which
      may be regarded as a reassortant-limiting factor probably significant for virus
      evolution.

PMID- 9559531
TI  - [Formation of humoral and secretory immunity in elderly persons with different
      schemes of immunization with flu vaccines].
AB  - The immunological efficacy of 5 protocols of immunization with two influenza
      vaccines are compared in 168 elderly subjects aged 64 to 87 years. Russian live
      cold-adapted reassortant trivalent (LCIV) and American inactivated cleaved
      trivalent (ICIV) influenza vaccines were used. The protocols of vaccination were
      as follows: 1) simultaneous vaccination with LCIV and ICIV and revaccination with
      LCIV after 1 months; 2) simultaneous vaccination with LCIV and ICIV and
      revaccination with placebo after 1 month; 3) vaccination and revaccination with
      LCIV; 4) vaccination with ICIV and revaccination with placebo; 5) vaccination and
      revaccination with placebo preparation (control); 6) vaccination with ICIV and
      revaccination with LCIV after 1 month. The incidence of significant increments
      and intensity of accumulation of serum (assessed by the hemagglutination
      inhibition test) and secretory (IgA) antibodies (assessed by enzyme immunoassay)
      was evaluated. For elderly subjects, simultancous vaccination with LCIV and ICIV
      followed by revaccination with LCIV is the most effective. After such
      vaccinations both secretory and humoral immune responses are characterized by the
      highest production of secretory IgA and serum antibodies. The quantitative
      parameters of both types of immune response in elderly subjects thus immunized
      are much higher than in young subjects vaccinated traditionally, that is, by LCIV
      or ICIV alone.

PMID- 9559532
TI  - [Role of certain factors in intracellular oligomerization of influenza virus
      nucleoproteins].
AB  - Oligomerization of influenza virus nucleoprotein (NP) depends on the virus
      strain. NP monomers of viruses A/Duck/Ukraine/63 (H3N8) and
      A/Seal/Massachusets/1/80/ (H7N7) are oligomerized completely. The A/USSR/90/77
      virus (H1N1) NP is characterized by just partial oligomerization, similarly as a
      reassortant containing surface protein genes of virus A/Duck/Ukraine and internal
      protein genes of A/USSR/90 virus. Hence, it is probable that NP gene controls the
      type of NP oligomerization. NP oligomerization is shown to depend on the
      temperature, the optimal t = 37 degrees C, but not on the type of cells or
      intracellular concentration of total NP. NP oligomers forming in vivo are
      believed to differ from NP oligomers formed in vitro described previously.

PMID- 9559533
TI  - [Comparative analysis of distribution of mutant alleles of the gene coding for
      the CCR-5 chemokine receptor, among people in Russia, infected and not infected
      with HIV-1].
AB  - Comparative analysis of the distribution of deletion mutations of CC-chemokine
      receptor 5 (CCR-5) gene among HIV-1 infected and not infected subjects in Russia
      showed the incidence of the heterozygous genotype to be 17.8% among both HIV
      infected and seronegative subjects. The incidence of the homozygous genotype for
      the deletion among seronegative individuals was 0.6%, but no homozygotes were
      found among HIV-1 infected patients. Study of the incidence of the mutant CCR-5
      allele among patients infected with different HIV-1 subtypes showed that the
      susceptibility of heterozygotes to HIV-1 infection was not associated with any
      special genetic subtype.

PMID- 9559534
TI  - [Characteristics of the LTR of endogenous retrovirus in the human T-lymphocyte
      CD4 receptor gene].
AB  - The nucleotide sequence of the long terminal repeat (LTR) of human endogenous
      retrovirus element (HERV), localized in the first introne of the CD4 gene in the
      antisense direction, is determined. This new retrotransposon is highly homologous
      with different LTR HERV and belongs to HERV-K family. A peculiar feature of this
      element is an insertion of the Alu repeated sequence inside LTR. This Alu repeat
      has the same orientation as LTR HERV and contains two short open frames with a
      high level of homology with DAF (decay accelerating factor) proteins and the
      fifth complement component. In addition, this Alu repeat of LTR HERV contains
      regulatory elements: enhancer, TATAA box, poly A site, etc. Preservation of
      putative regulatory elements in the LTR suggests that they can render distinct
      regulatory properties to CD4 receptor gene.

PMID- 9559535
TI  - [Isolation of a complex of tick-borne encephalitis viral proteins by affinity
      chromatography using monoclonal antibodies to proteins NS5 and NS3].
AB  - Affinity chromatography of lysates of continuous porcine embryo cells infected
      with tick-borne encephalitis (TBE) virus on sepharose with immobilized monoclonal
      antibodies to TBE virus proteins NS5 and NS3 results in isolation of a stable
      protein complex. This complex contains viral proteins NS5, NS3, p49, and,
      probably, two more cell proteins. This complex is not detected at the early stage
      of infection, and 24 h after infection its structure does not depend on the
      specificity of immobilized monoclonal antibodies used in affinity chromatography
      and on the time elapsed after the infection. Immunoprecipitates of infected cells
      phosphorylated TBE virus protein NS5 in vitro, but possessed no RNA-polymerase
      activity. Elution of the complex with buffers with pH 3.5 or 11.1 or with 2M urea
      failed to purify the active replicase. The complex of viral and cellular proteins
      isolated by affinity chromatography on different immunoadsorbents did not possess
      RNA-polymerase activity because of inactivation or absence of additional
      subunit(s).

PMID- 9559537
TI  - [Influenza pandemic: can we fight it?].

PMID- 9559536
TI  - [Some mechanisms of the action of oligonucleotides: stimulation of the immune
      system and decreased infection of the brain in tickborne encephalitis].
AB  - Morphological changes in the thymus, spleen, and brain are analyzed in white mice
      injected 16-component oligonucleotide (ON) pE16 complementary to the NS3 protein
      gene sequences of tickborne encephalitis (TBE) virus in doses of 1 to 0.001 nM.
      ON stimulated thymic and splenic cells. Besides the stimulating effect, injection
      of ON to mice infected with TBE enhanced the destruction of lymphocytes and
      boosted the macrophagal activity, which was paralleled by a decrease in the
      intensity of virus-specific injuries in the brain. Thus, the antiviral activity
      of ON may be due to not only the fact that it is complementary to the TBE virus
      genome, but to stimulation of the immune system, specifically, the thymus and T
      related elements, as well.

PMID- 9559538
TI  - [Epizootic situation with regard to rabies in the Moscow area and a way to
      improve it].

PMID- 9559539
TI  - Mam33p, an oligomeric, acidic protein in the mitochondrial matrix of
      Saccharomyces cerevisiae is related to the human complement receptor gC1q-R.
AB  - Mam33p (mitochondrial acidic matrix protein) is a soluble protein, located in
      mitochondria of Saccharomyces cerevisiae. It is synthesized as a precursor with
      an N-terminal mitochondrial targeting sequence that is processed on import.
      Mam33p assembles to a homo-oligomeric complex in the mitochondrial matrix. It can
      bind to the sorting signal of cytochrome b2 that directs this protein into the
      intermembrane space. Mam33p is encoded by an 801 bp open reading frame. Gene
      disruption did not result in a significant growth defect. Mam33p exhibits
      sequence similarity to gC1q-R, a human protein that has been implicated in the
      binding of complement factor C1q and kininogen.

PMID- 9559540
TI  - Synthesis of monohydroxylated inositolphosphorylceramide (IPC-C) in Saccharomyces
      cerevisiae requires Scs7p, a protein with both a cytochrome b5-like domain and a
      hydroxylase/desaturase domain.
AB  - Saccharomyces cerevisiae mutants lacking Scs7p fail to accumulate the
      inositolphosphorylceramide (IPC) species. IPC-C, which is the predominant form
      found in wild-type cells. Instead scs7 mutants accumulate an IPC-B species
      believed to be unhydroxylated on the amide-linked C26-fatty acid. Elimination of
      the SCS7 gene suppresses the Ca(2+)-sensitive phenotype of csg1 and csg2 mutants.
      The CSG1 and CSG2 genes are required for mannosylation of IPC-C and accumulation
      of IPC-C by the csg mutants renders them Ca(2+)-sensitive. The SCS7 gene encodes
      a protein that contains both a cytochrome b5-like domain and a domain that
      resembles the family of cytochrome b5-dependent enzymes that use iron and oxygen
      to catalyse desaturation or hydroxylation of fatty acids and sterols. Scs7p is
      therefore likely to be the enzyme that hydroxylates the C26-fatty acid of IPC-C.

PMID- 9559541
TI  - Assembly of phosphofructokinase-1 from Saccharomyces cerevisiae in extracts of
      single-deletion mutants.
AB  - Phosphofructokinase-1 from Saccharomyces cerevisiae is an octameric enzyme
      comprising two non-identical subunits, alpha and beta, which are encoded by the
      unlinked genes PFK1 and PFK2. In this paper, assembly and reactivation of the
      enzyme have been studied in cell-free extracts of single-deletion mutants. In
      contrast to the previously described lack of phosphofructokinase-1 activity in
      cell-free extracts of these mutants, we could measure a temporary enzyme activity
      immediately after lysis of protoplasts. This result supports the assumption that
      each of the subunits forms an enzyme structure which is active in vivo but not
      stable after cell disruption. Upon mixing of separately prepared cell-free
      extracts of both deletion mutants very low activity could be measured. About 40%
      of the wild-type activity was regained when both mutants were mixed prior to
      disruption. The reactivation rate could be slightly increased by addition of ATP
      and fructose 6-phosphate and was found to be a function of the growth state,
      particularly of the beta-subunit-carrying cells. The individual subunits did not
      interact with Cibacron Blue F3G-A, a biomimetic ligand of phosphofructokinase-1.
      After reassembly of both subunits in vitro a strong affinity of the reconstituted
      phosphofructokinase-1 to the dye-ligand was observed. The inability of the
      subunits to reconstitute under certain conditions seems to result from
      alterations of the intracellular environment following disruption. These changes
      give rise to induce an unproductive side reaction like self-aggregation of the
      subunits. Because reconstitution of phosphofructokinase-1 from S. cerevisiae
      behaves in a similar way to that of hemoglobin and luciferase, we would speculate
      a general mechanism for assembly of oligomeric proteins in vivo.

PMID- 9559542
TI  - Purified arginine permease of Candida albicans is functionally active in a
      reconstituted system.
AB  - We have for the first time purified arginine permease from a pathogenic yeast,
      Candida albicans, to homogeneity by affinity chromatography using L-arginine
      linked agarose matrix as affinity column. The purified protein (PP) was of 66 kDa
      with no subunit structure. Two kinetically distinct binding affinities of PP were
      evident where high affinity binding (S1) revealed a dependence on acidic pH while
      pH did not have dramatic effect on low affinity (S2) binding. The specificity of
      L-arginine binding to PP with regard to other amino acids, structural analogues
      and inhibitors, was essentially similar to arginine transport observed in the
      intact cells of C. albicans (Rao et al., 1986). The purified arginine permease
      was reconstituted into proteoliposomes and its functionality was tested by
      imposing a valinomycin-induced membrane potential. All the characteristic
      features of L-arginine transport displayed by the reconstituted system were
      similar to those observed in intact cells. Thus homogeneous purified arginine
      permease was also functionally active.

PMID- 9559543
TI  - The importance of the glycerol 3-phosphate shuttle during aerobic growth of
      Saccharomyces cerevisiae.
AB  - Maintenance of a cytoplasmic redox balance is a necessity for sustained cellular
      metabolism. Glycerol formation is the only way by which Saccharomyces cerevisiae
      can maintain this balance under anaerobic conditions. Aerobically, on the other
      hand, several different redox adjustment mechanisms exist, one of these being the
      glycerol 3-phosphate (G3P) shuttle. We have studied the importance of this
      shuttle under aerobic conditions by comparing growth properties and glycerol
      formation of a wild-type strain with that of gut2 delta mutants, lacking the FAD
      dependent glycerol 3-phosphate dehydrogenase, assuming that the consequent
      blocking of G3P oxidation is forcing the cells to produce glycerol from G3P. To
      impose different demands on the redox adjustment capability we used various
      carbon sources having different degrees of reduction. The results showed that the
      shuttle was used extensively with reduced substrate such as ethanol, whereas the
      more oxidized substrates lactate and pyruvate, did not provoke any activity of
      the shuttle. However, the absence of a functional G3P shuttle did not affect the
      growth rate or growth yield of the cells, not even during growth on ethanol.
      Presumably, there must be alternative systems for maintaining a cytoplasmic redox
      balance, e.g. the so-called external NADH dehydrogenase, located on the outer
      side of the inner mitochondrial membrane. By comparing the performance of the
      external NADH dehydrogenase and the G3P shuttle in isolated mitochondria, it was
      found that the former resulted in high respiratory rates but a comparably low P/O
      ratio of 1.2, whereas the shuttle gave low rates but a high P/O ratio of 1.7. Our
      results also demonstrated that of the two isoforms of NAD-dependent glycerol 3
      phosphate dehydrogenase, only the enzyme encoded by GPD1 appeared important for
      the shuttle, since the enhanced glycerol production that occurs in a gut2 delta
      strain proved dependent on GPD1 but not on GPD2.

PMID- 9559544
TI  - The SKS1 gene of Saccharomyces cerevisiae is required for long-term adaptation of
      snf3 null strains to low glucose.
AB  - The SKS1 gene was originally identified as a multicopy suppressor of the growth
      defect of snf3 null mutations on low glucose concentrations. Snf3p is required
      for the rapid induction of HXT2 during growth on low substrate concentrations.
      Loss of Snf3p leads to a dramatic delay in expression of HXT2. Adaptation to low
      substrate concentrations does not occur in snf3 sks1 double null mutant strains,
      suggesting that SKS1 is required for the glucose-dependent expression of HXT2 in
      the absence of Snf3p activity. Over-expression of SKS1 leads to over-expression
      of Hxt2p, thus explaining the mechanism of suppression of the snf3 defect. SKS1
      defines a novel, Snf3p-independent pathway for the expression of Hxt2p. Under
      certain growth conditions, over-expression of SKS1 itself leads to a growth
      defect which is diminished in snf3 hxt2 double mutants. This suggests that over
      expression of Hxt2p at physiologically inappropriate times is detrimental to the
      cells.

PMID- 9559545
TI  - Glycosylation of human alpha 1-antitrypsin in Saccharomyces cerevisiae and
      methylotrophic yeasts.
AB  - Human alpha 1-antitrypsin (alpha 1-AT) is a major serine protease inhibitor in
      plasma, secreted as a glycoprotein with a complex type of carbohydrate at three
      asparagine residues. To study glycosylation of heterologous proteins in yeast, we
      investigated the glycosylation pattern of the human alpha 1-AT secreted in the
      baker's yeast Saccharomyces cerevisiae and in the methylotrophic yeasts,
      Hansenula polymorpha and Pichia pastoris. The partial digestion of the
      recombinant alpha 1-AT with endoglycosidase H and the expression in the mnn9
      deletion mutant of S. cerevisiae showed that the recombinant alpha 1-AT secreted
      in S. cerevisiae was heterogeneous, consisting of molecules containing core
      carbohydrates on either two or all three asparagine residues. Besides the core
      carbohydrates, variable numbers of mannose outer chains were also added to some
      of the secreted alpha 1-AT. The human alpha 1-AT secreted in both methylotrophic
      yeasts was also heterogeneous and hypermannosylated as observed in S. cerevisiae,
      although the overall length of mannose outer chains of alpha 1-AT in the
      methylotrophic yeasts appeared to be relatively shorter than those of alpha 1-AT
      in S. cerevisiae. The alpha 1-AT secreted from both methylotrophic yeasts
      retained its biological activity as an elastase inhibitor comparable to that of
      alpha 1-AT from S. cerevisiae, suggesting that the different glycosylation
      profile does not affect the in vitro activity of the protein.

PMID- 9559546
TI  - Purification and properties of polyphosphatase from Saccharomyces cerevisiae
      cytosol.
AB  - A homogenous polyphosphatase preparation was obtained from Saccharomyces
      cerevisiae cytosol with a 3.8% yield and 3540-fold purification. The enzyme
      hydrolysed polyphosphate (polyP) with various chain lengths, including polyP3,
      and split Pi off the end of the chain. It was inactive with respect to ATP, PPi,
      and p-nitrophenylphosphate. Its specific activity with polyP15 was 283 U/mg
      protein. The polyphosphatase was a monomeric protein with a molecular mass of 40
      kDa. This enzyme was inactive without divalent cations and with Cu2+ and Ca2+.
      The ability of other divalent cations to activate the enzyme decreased in the
      following order; Co2+ > Mn2+ > Mg2+ > Zn2+. A kinetic model of the hydrolysis of
      polyP3 and action of Mg2+ is proposed.

PMID- 9559547
TI  - Construction of PCR-ligated long flanking homology cassettes for use in the
      functional analysis of six unknown open reading frames from the left and right
      arms of Saccharomyces cerevisiae chromosome XV.
AB  - Six open reading frames (ORFs) of unknown function from Saccharomyces cerevisiae
      chromosome XV, three from the left and three from the right arm, were deleted in
      two diploid strains by the short flanking homology method (Wach et al., 1994).
      Transformants were selected as Geneticin (G418)-resistant colonies and correct
      integration of the kanMX4 cassette was checked by colony PCR. Following
      sporulation of the diploids, tetrads were dissected and scored for the
      segregation of the G418-resistant marker. We have developed a widely applicable
      method for the construction of gap repair plasmids to obtain the cognate clones
      for each of the disrupted ORFs. The 5'- and 3'-flanks of the ORF in question are
      linked by a unique restriction endonuclease. When the plasmid is cut at this site
      it can be used to obtain, by selection for the appropriate antibiotic resistance,
      long flanking homology (LFH) cassettes containing the cognate clone or the
      disrupted allele. The LFH cassette containing the cognate clone or the disrupted
      allele can be released from the gap-repaired plasmid by cutting at the inserted
      flanking restriction sites. One of the six ORFs (YOR319w) corresponds to an
      essential gene whose product is part of the spliceosome complex. Haploid as well
      as homozygous and heterozygous diploid disruptant strains for each of the five
      non-essential ORFs were subjected to growth test on different media at 15 degrees
      C, 30 degrees C and 37 degrees C. Disruption of YOR322c causes osmotically
      sensitive growth on YEPD at 37 degrees C and the product of YOL091w appears to
      play a role in sporulation since the homozygous diploid disruptant has lost the
      ability to sporulate.

PMID- 9559548
TI  - Isolation and characterization of Kluyveromyces marxianus mutants deficient in
      malate transport.
AB  - In malic acid-grown cells of the strains ATCC 10022 and KMS3 of Kluyveromyces
      marxianus the transport of malic acid occurred by a malate-proton symport, which
      accepted L-malic, D-malic, succinic and fumaric acids, but not tartaric, malonic
      or maleic acids. The system was inducible and subjected to glucose repression.
      Mutants of the strain KMS3, unable to grow in a medium with malic acid, were
      isolated and checked for their capacity to utilize several carbon sources and to
      transport dicarboxylic acids by the malate-proton symport. Two distinct clones
      affected on malate transport were obtained. Both were able to grow on a medium
      with glycerol or ethanol but not with DL-malic, succinic, oxoglutaric and
      oxaloacetic acids as the sole carbon and energy sources. However, while one of
      the mutants (Mal7) displayed activity levels for the enzymes malate
      dehydrogenase, isocitrate lyase, and phosphoenolpyruvate carboxykinase similar to
      those of the wild strain, in the other mutant type (Mal6) the activities for the
      same enzymes were significantly reduced. Plasma membranes from derepressed cells
      of the wild strain and of the mutants Mal6 and Mal7 were isolated and the protein
      analysed by SDS-PAGE. The electrophoretic patterns of these preparations differed
      in a polypeptide with an apparent molecular mass of about 28 kDa, which was
      absent only in the mutant Mal7. The results indicated that Mal7 can be affected
      in a gene that encodes a malate carrier in K. marxianus.

PMID- 9559549
TI  - Identification and analysis of homologues of Saccharomyces cerevisiae Spt3
      suggest conserved functional domains.
AB  - Spt3 of Saccharomyces cerevisiae is a factor required for normal transcription
      from particular RNA polymerase II-dependent promoters. As a step towards
      analysing Spt3 structure-function relationships, we have identified and studied
      Spt3 homologues from three other yeasts: Kluyveromyces lactis, Clavispora
      opuntiae and Schizosaccharomyces pombe. Alignment of their predicted amino acid
      sequences shows an overall identity of 30% between all four homologues and
      suggests that three conserved domains are present in Spt3. When tested for
      function in S. cerevisiae, K. lactis SPT3 was shown to fully complement and S.
      pombe SPT3 to partially complement an spt3 delta mutation. These data demonstrate
      that Spt3 is functionally conserved among distantly related yeasts.

PMID- 9559550
TI  - Heat shock transiently enhances the synthesis rate of Sis1p, a ribosome
      associated DnaJ protein in the oleagenous yeast Apiotrichum curvatum.
AB  - DnaJ proteins have been localized in different intracellular compartments of
      eukaryotes. In Apiotrichum curvatum, a fat-storing yeast, we found a DnaJ homolog
      associated with ribosomes and large cytosolic complexes as well. Using a plant
      DnaJ probe and a cDNA library constructed from poly(A)(+)-RNA of A. curvatum
      grown on oleate we isolated a SIS1 cDNA coding for a 39.5 kDa protein. The
      putative protein contains neither a zinc finger motif nor a CAAX motif but is
      characterized by a J-domain at the N-terminal region and a large G-rich region in
      the middle part of the molecule. Heat shock applied for 1 h resulted in a
      pronounced but transient increase of the SIS1 mRNA. An antiserum was raised
      against the bacterially expressed protein. Cell fractions from A. curvatum were
      further separated by sedimentation centrifugation on sucrose gradients. Analysing
      the sub-fractions, we detected Sis1p mainly associated with ribosomes, and with
      particles sedimenting at approximately 200S. Hsp70 was found to be associated
      with the 200S fraction. The respective cytosolic A. curvatum Hsp70 cDNA was
      cloned and sequenced. High salt conditions caused the removal of Hsp70 and Sis1p
      from the 200S complexes. Mild RNase treatment of the 200S fraction afforded
      monosomes and 200S complexes unaffected by RNase. Heat shock led to a pronounced
      increase in the rate of de novo synthesis. However, due to the large pools of
      Sis1p on ribosomes and large cytosolic complexes, the increase in gene activation
      did not lead to a significant change of the total amount of Sis1p.

PMID- 9559551
TI  - Application of mRNA differential display to investigate gene expression in
      thermotolerant cells of Saccharomyces cerevisiae.
AB  - We have described the use of differential display of PCR-amplified reverse
      transcribed mRNA (DDRT-PCR) to survey changes in gene expression profiles induced
      by heat shock and carbon catabolite derepression in Saccharomyces cerevisiae. It
      is well established that either of these states elicits thermotolerant
      phenotypes. An initial analysis conducted on cells of an inherently
      thermosensitive strain (Ysen) indicated that approximately 10% of the total
      number of cDNAs detected were either up or down regulated following heat shock at
      37 degrees C (30 min) in comparison to control cells (25 degrees C). In addition,
      whereas 7% of all PCR products were preferentially expressed during derepressive
      growth, approximately 2% were found to be common to both heat-shocked and
      derepressed cells. A repeat analysis, performed on all three cell types of Ysen
      as well as cells of a relatively thermoresistant strain (Yres) yielded 30
      differentially displayed cDNA fragments common to heat-shocked and derepressed
      cells of both strains. Eighteen of these generated signals on Northern blots, of
      which three were confirmed as regulated. Five amplicons, including one not
      detected by Northern analysis and another from the derepressed state, were cloned
      and sequenced. Three of these exhibited homology to S. cerevisiae genes with well
      characterized protein products: HSP 90, HXK1 and STA1. The remaining two
      applicons showed nucleotide identity to YTIS11, a homolog of the mammalian TIS11
      and putative transcriptional activator, and an orphan gene encoding a
      hypothetical transmembrane protein belonging to the multi-drug resistance
      translocase family. Our novel application of DDRT-PCR has identified new and
      known genes that may be further evaluated as factors involved in stress
      regulation and has demonstrated the potential of the technique to systematically
      analyse gene expression in yeast.

PMID- 9559552
TI  - Evolution of gene order and chromosome number in Saccharomyces, Kluyveromyces and
      related fungi.
AB  - The extent to which the order of genes along chromosomes is conserved between
      Saccharomyces cerevisiae and related species was studied by analysing data from
      DNA sequence database. As expected, the extent of gene order conservation
      decreases with increasing evolutionary distance. About 59% of adjacent gene pairs
      in Kluyveromyces lactis or K. marxianus are also adjacent in S. cerevisiae, and a
      further 16% of Kluyveromyces neighbours can be explained in terms of the inferred
      ancestral gene order in Saccharomyces prior to the occurrence of an ancient whole
      genome duplication. Only 13% of Candida albicans linkages, and no
      Schizosaccharomyces pombe linkages, are conserved. Analysis of gene order
      arrangements, chromosome numbers, and ribosomal RNA sequences suggests that
      genome duplication occurred before the divergence of the four species in
      Saccharomyces sensu stricto (all of which have 16 chromosomes), but after this
      lineage had diverged from Saccharomyces kluyveri and the Kluyveromyces
      lactislmarxianus species assemblage.

PMID- 9559553
TI  - Regulation of alcoholic fermentation in batch and chemostat cultures of
      Kluyveromyces lactis CBS 2359.
AB  - Kluyveromyces lactis is an important industrial yeast, as well as a popular
      laboratory model. There is currently no consensus in the literature on the
      physiology of this yeast, in particular with respect to aerobic alcoholic
      fermentation ('Crabtree effect'). This study deals with regulation of alcoholic
      fermentation in K. lactis CBS 2359, a proposed reference strain for molecular
      studies. In aerobic, glucose-limited chemostate cultures (D = 0.05-0.40 h-1)
      growth was entirely respiratory, without significant accumulation of ethanol or
      other metabolities. Alcoholic fermentation occurred in glucose-grown shake-flask
      cultures, but was absent during batch cultivation on glucose in fermenters under
      strictly aerobic conditions. This indicated that ethanol formation in the shake
      flask cultures resulted from oxygen limitation. Indeed, when the oxygen feed to
      steady-state chemostat cultures (D = 0.10 h-1) was lowered, a mixed
      respirofermentative metabolism only occurred at very low dissolved oxygen
      concentrations (less than 1% of air saturation). The onset of respirofermentative
      metabolism as a result of oxygen limitation was accompanied by an increase of the
      levels of pyruvate decarboxylase and alcohol dehydrogenase. When aerobic, glucose
      limited chemostat cultures (D = 0.10 h-1) were pulsed with excess glucose,
      ethanol production did not occur during the first 40 min after the pulse.
      However, a slow aerobic ethanol formation was invariably observed after this
      period. Since alcoholic fermentation did not occur in aerobic batch cultures this
      is probably a transient response, caused by an imbalanced adjustment of enzyme
      levels during the transition from steady-state growth at mu = 0.10 h to growth at
      mu max. It is concluded that in K. lactis, as in other Crabtree-negative yeasts,
      the primary environmental trigger for occurrence of alcoholic fermentation is
      oxygen limitation.

PMID- 9559554
TI  - The list of cytoplasmic ribosomal proteins of Saccharomyces cerevisiae.
AB  - Screening of the complete genome sequence from the yeast Saccharomyces cerevisiae
      has enabled us to compile a complete list of the genes encoding cytoplasmic
      ribosomal proteins in this organism. Putative ribosomal protein genes were
      selected primarily on the basis of the sequence similarity of their products with
      ribosomal proteins from other eukaryotic organisms, in particular the rat. These
      genes were subsequently screened for typical yeast rp-gene characteristics, viz.
      (1) a high codon adaptation index; (2) their promoter structure and (3) their
      responses to changes in growth conditions. The yeast genome appears to carry 78
      different genes, of which 59 are duplicated, encoding 32 different small-subunit
      and 46 large-subunit proteins. A new nomenclature for these ribosomal proteins is
      proposed.

PMID- 9559555
TI  - Nucleotide sequence of the Schizosaccharomyces pombe lys1+ gene and similarities
      of the lys1+ protein to peptide antibiotic synthetases.
AB  - The 4.2 kbp lys1+ gene of Schizosaccharomyces pombe encoding the large subunit of
      alpha-aminoadipate reductase (EC1.2.1.31), an enzyme specific to lysine synthesis
      in higher fungi, was completely sequenced at the nucleotide level from pLYS1H.
      The S. pombe lys1+ gene product consists of 1415 amino acid residues and has a
      putative molecular weight of 155.8 kDa. The encoded protein converts alpha
      aminoadipic acid to alpha-aminoadipate-delta-semialdehyde by an ATP-mediated
      adenylation. Analysis of the sequence showed that the putative protein encoded by
      lys1+ shares strong homology with the peptide antibiotic synthetases which also
      use in adenylation step.

PMID- 9559556
TI  - Characterization of the Prk1 protein kinase from Schizosaccharomyces pombe.
AB  - We report the isolation and characterization of a protein kinase from the fission
      yeast Schizosaccharomyces pombe. The proposed Prk1 protein contains 352 amino
      acids and has significant homology to the Ume5p kinase (also known as Srb10p,
      Ssn3p and Are1p) of the budding yeast Saccharomyces cerevisiae, a cyclin
      dependent kinase involved in regulating the transcription of a diverse set of
      genes. Disruption of the prk1 gene increases flocculation but does not appear to
      have any other significant effect on cell behaviour. This defect can be overcome
      by expressing the UME5 gene, indicating that Prk1 is the fission yeast homologue
      of Ume5p.

PMID- 9559557
TI  - Current awareness on yeast.

PMID- 9559558
TI  - Cloning and characterization of high-CO2-specific cDNAs from a marine microalga,
      Chlorococcum littorale, and effect of CO2 concentration and iron deficiency on
      the gene expression.
AB  - Two cDNA clones exclusively induced under an extremely high-CO2 concentration
      (20%) were isolated from Chlorococcum littorale by differential screening and
      named HCR (high-CO2 response) 1 and 2, respectively. The amino acid sequence of
      the protein encoded by HCR2 exhibited homology to the gp91-phox protein, a
      critical component of a human phagocyte oxidoreductase, and to the yeast ferric
      reductases, Saccharomyces cerevisiae FRE1 and FRE2 and Schizosaccharomyces pombe
      Frp1. The induction of both HCR mRNAs required extremely high-CO2 conditions and
      iron deficiency, being suppressed under air conditions and by iron sufficiency,
      suggesting that the expression of these two HCR genes required extremely high-CO2
      conditions and iron deficiency in combination. The HCR2 protein was detected in
      the membrane fractions of cells grown under conditions which would favor the
      induction of HCR2-mRNA and the protein level was lowered when the cells were
      transferred from iron deficient to 10 microM FeSO4 conditions (with 20% CO2).

PMID- 9559559
TI  - A protein encoded by din1, a dark-inducible and senescence-associated gene of
      radish, can be imported by isolated chloroplasts and has sequence similarity to
      sulfide dehydrogenase and other small stress proteins.
AB  - In an attempt to isolate cDNA clones for dark-inducible chloroplast proteins, we
      screened a cDNA library which was prepared from radish cotyledons by a two-step
      method. The source plants were grown under continuous light for 14 d and kept in
      darkness for 24 h. One of the selected clones, S2D12, corresponded to the din1
      gene which we previously reported as a dark-inducible, senescence-associated gene
      [Azumi and Watanabe (1991) Plant Physiol. 95:577]. A 22 kDa polypeptide was
      produced from the cDNA in an in vitro expression system in the presence of
      [35S]methionine. This polypeptide was capable of being imported by isolated
      chloroplasts, processed to a smaller mature form and localized in the stromal
      fraction. As the amino acid sequence of the putative mature protein has no
      homology to any known chloroplast protein, din1 was suggested to be the first
      gene for a chloroplast protein which is negatively controlled by light. The
      putative mature protein has similarity to sulfide dehydrogenase from Wolinella
      succinogenes and other small stress proteins; glpE and pspE from Escherichia coli
      and hsp67B2 from Drosophila melanogaster.

PMID- 9559560
TI  - Identification of a novel triterpenoid saponin from Pisum sativum as a specific
      inhibitor of the diguanylate cyclase of Acetobacter xylinum.
AB  - A specific and highly potent inhibitor of diguanylate cyclase, the key regulatory
      enzyme of the cellulose synthesizing apparatus in the bacterium Acetobacter
      xylinum, was isolated from extracts of etiolated pea shoots (Pisum sativum). The
      inhibitor has been purified by a multistep procedure, and sufficient amounts of
      highly purified compound (3-8 mg) for spectral analysis were obtained. The
      structure of this compound was established as 3-O-alpha-L-rhamnopyranosyl-(1-->2)
      beta-D-galactopyranosyl-(1--> 2)-beta-D-glucuronopyranosyl soyasapogenol B 22-O
      alpha-D-glucopyranoside. The structure was elucidated on the basis of
      susceptibility to various enzymes, chemical and spectral methods, such as GC-MS,
      FAB-MS, and the following types of 2D-NMR: COSY, ROESY, TOCSEY, HMQC, HMBC
      analyses. An identical or a very similar compound with identical biological
      activity was also isolated from A. xylinum, strongly suggesting that at least
      certain aspects of cellulose synthesis in the bacteria and in higher plants may
      be regulated in a similar manner. The content of this saponin in etiolated plants
      was about 0.04 mumol (g fresh tissue)-1.

PMID- 9559561
TI  - Cloning of the gene encoding a protochlorophyllide reductase: the physiological
      significance of the co-existence of light-dependent and -independent
      protochlorophyllide reduction systems in the cyanobacterium Plectonema boryanum.
AB  - Cyanobacteria have two protochlorophyllide (Pchlide) reductases catalyzing the
      conversion of Pchlide to chlorophyllide, a key step in the biosynthetic pathway
      of chlorophylls (Chls); a light-dependent (LPOR) and a light-independent (DPOR)
      reductase. We found an open reading frame (ORF322) in a 2,131-bp EcoRI fragment
      from the genomic DNA of the cyanobacterium Plectonema boryanum. Because the
      deduced amino acid sequence showed a high similarity to those of various plant
      LPORs and the LPOR activity was detected in the soluble fraction of Escherichia
      coli cells over-expressing the ORF322 protein, ORF322 was defined as the por gene
      encoding LPOR in P. boryanum. A por-disrupted mutant, YFP12, was isolated by
      targeted mutagenesis to investigate the physiological importance of LPOR. YFP12
      grew as well as wild type under low light conditions (10-25 muE m-2 s-1).
      However, its growth was significantly retarded as a result of a significant
      decrease in its Chl content under higher light conditions (85-130 muE m-2 s-1).
      Furthermore, YFP12 stopped growing and suffered from photobleaching under the
      highest light intensity (170 muE m-2 s-1). In contrast, a chlL-disrupted (DPOR
      less) mutant YFC2 grew as well as wild type irrespective of light intensity. From
      these phenotypic characteristics, we concluded that, although both LPOR and DPOR
      contribute to Chl synthesis in the cells growing in the light, the extent of the
      contribution by LPOR increases with increasing light intensity; without it, the
      cells are unable to grow under light intensities of more than 130 muE m-2 s-1.

PMID- 9559562
TI  - Glyoxysomal malate dehydrogenase in pumpkin: cloning of a cDNA and functional
      analysis of its presequence.
AB  - Glyoxysomal malate dehydrogenase (gMDH) is an enzyme of the glyoxylate cycle that
      participates in degradation of storage oil. We have cloned a cDNA for gMDH from
      etiolated pumpkin cotyledons that encodes a polypeptide consisting of 356 amino
      acid residues. The nucleotide and N-terminal amino acid sequences revealed that
      gMDH is synthesized as a precursor with an N-terminal extrapeptide. The N
      terminal presequence of 36 amino acid residues contains two regions homologous to
      those of other microbody proteins, which are also synthesized as large
      precursors. To investigate the functions of the N-terminal presequence of gMDH,
      we generated transgenic Arabidopsis that expressed a chimeric protein consisting
      of beta-glucuronidase and the N-terminal region of gMDH. Immunological and
      immunocytochemical studies revealed that the chimeric protein was imported into
      microbodies such as glyoxysomes and leaf peroxisomes and was then subsequently
      processed. Site-directed mutagenesis studies showed that the conserved amino
      acids in the N-terminal presequence, Arg-10 and His-17, function as recognition
      sites for the targeting to plant microbodies, and Cys-36 in the presequence is
      responsible for its processing. These results correspond to those from the
      analyses of glyoxysomal citrate synthase (gCS), which was also synthesized as a
      large precursor, suggesting that common mechanisms that can recognize the
      targeting or the processing of gMDH and gCS function in higher plant cells.

PMID- 9559563
TI  - An mRNA of tobacco cell, which is rapidly inducible by methyl jasmonate in the
      presence of cycloheximide, codes for a putative glycosyltransferase.
AB  - Two-dimensional gel electrophoretic display of polypeptides labeled in vivo and
      those synthesized in vitro from poly(A)(+)-RNA indicated that treatment of
      cultured cells of tobacco (Nicotiana tabacum) BY-2 with methyl jasmonate (MeJA)
      induces accumulation of a limited number of specific mRNAs within a few hours.
      The MeJA-induction of most of these mRNAs was inhibited by cycloheximide (CHX).
      Six MeJA-inducible cDNAs identified by differential screening were classified
      into three groups based on the sensitivity of their induction to CHX. Induction
      of group I mRNAs by MeJA occurred earlier than the induction of other mRNAs and
      it was not inhibited by CHX. The induction of group II mRNAs by MeJA was blocked
      by CHX, while group III mRNAs were induced by CHX alone. One group I cDNA was
      found to encode a putative protein, JIGT, homologous to UDP-sugar
      glycosyltransferases previously characterized from several plant species. JIGT
      was structurally different from a putative glycosyltransferase that is rapidly
      inducible by salycylic acid (SA) in BY-2 cells. JIGT mRNA was not induced by SA.
      In addition to MeJA, as little as 10(-9) M coronatine induced JIGT mRNA. A
      sequence highly homologous to JIGT is present as a single copy in the genomes of
      Nicotiana sylvestris and N. tomentosiformis. The MeJA-inducible production of
      JIGT may be involved in sugar-conjugation of an unknown substrate in a defensive
      response and expression of the gene for JIGT in BY-2 cells might serve as a good
      model system for disecting molecular events occurring in JA-inducible gene
      expression.

PMID- 9559564
TI  - Distribution of fallover in the carboxylase reaction and fallover-inducible sites
      among ribulose 1,5-bisphosphate carboxylase/oxygenases of photosynthetic
      organisms.
AB  - The biphasic reaction course, fallover, of carboxylation catalysed by ribulose
      1,5-bisphosphate carboxylase/oxygenase (RuBisCO) has been known as a
      characteristic of the enzyme from higher land plants. Fallover consists of
      hysteresis in the reaction seen during the initial several minutes and a very
      slow suicide inhibition by inhibitors formed from the substrate ribulose-1,5
      bisphosphate (RuBP). This study examined the relationship between occurrence of
      fallover and non-catalytic RuBP-binding sites, and the putative hysteresis
      inducible sites (Lys-21 and Lys-305 of the large subunit in spinach RuBisCO)
      amongst RuBisCOs of a wide variety of photosynthetic organisms. Fallover could be
      detected by following the course of the carboxylase reaction at 1 mM RuBP and the
      non-catalytic binding sites by alleviation of fallover at 5 mM RuBP. RuBisCO from
      Euglena gracilis showed the same linear reaction course at both RuBP
      concentrations, indicating an association between an absence of fallover and an
      absence of the non-catalytic binding sites. This was supported by the results of
      an equilibrium binding assay for this enzyme with a transition state analogue.
      Green macroalgae and non-green algae contained the plant-type, fallover enzyme.
      RuBisCOs from Conjugatae, Closterium ehrenbergii, Gonatozygon monotaenium and
      Netrium digitus, showed a much smaller decrease in activity at 1 mM RuBP than the
      spinach enzyme and the reaction courses of these enzymes at 5 mM RuBP were almost
      linear. RuBisCO of a primitive type Conjugatae, Mesotaenium caldariorum, showed
      the same linear course at both RuBP concentrations. Sequencing of rbcL of these
      organisms indicated that Lys-305 was changed into arginine with Lys-21 conserved.

PMID- 9559566
TI  - Characterization of delta 9 acyl-lipid desaturase homologues from Arabidopsis
      thaliana.
AB  - Two cDNAs, ADS1 and ADS2, were isolated from Arabidopsis. These cDNAs encoded
      proteins homologous to delta 9 acyl-lipid desaturases of cyanobacteria and acyl
      CoA desaturases of yeast and mammals. The expression of ADS1 and ADS2 was organ
      dependent. Cold temperature up-regulated the ADS2 expression, whereas it down
      regulated the ADS1 expression.

PMID- 9559567
TI  - Assessment of particle size distributions of health-relevant aerosol exposures of
      primary lead smelter workers.
AB  - Experiments were conducted at a primary lead smelter to investigate the particle
      size distributions of lead-containing aerosol to which workers were exposed,
      using personal inhalable dust spectrometers (PIDS) in specific smelter process
      areas. A total of 46 PIDS samples were evaluated, taken from the ore
      storage/mill, sinter plant, blast furnace and dross furnace process areas.
      Continuous particle size distributions were derived from the raw PIDS data
      employing a recently-developed optimisation routine, enabling determination of
      the percentages of inhalable, thoracic and respirable aerosol (in terms of lead
      content) as fractions of total lead aerosol. In addition, the mass ratios
      thoracic/inhalable and respirable/inhalable were also determined. Although the
      parameters of the measured particle size distributions ranged widely, some clear
      trends emerged. Firstly, the aerosols were coarser than had been expected based
      on measurements of previously reported workplace particle size distributions.
      This is thought to be due to the fact that the PIDS collects larger particles
      more efficiently than other instruments which have been used for such
      measurements. Secondly, there were significant differences in particle size
      distribution between process areas, in particular that the aerosol in the blast
      furnace area was generally finer than in the sinter plant. Such results may be
      used to support the results of workplace studies (reported elsewhere) into the
      differences between exposures to inhalable and 'total' aerosol as measured using
      different sampling instruments, especially when they are used together with
      knowledge of the physical processes governing the performances of such
      instruments.

PMID- 9559565
TI  - Characterization of a cDNA encoding CuZn-superoxide dismutase from the liverwort
      Marchantia paleacea var. diptera.
AB  - Suspension-cultured cells of the liverwort Marchantia paleacea var. diptera
      contain a cytosolic CuZn-superoxide dismutase (SOD) whose N-terminal amino acid
      sequence is similar to those of the isozymes found in chloroplasts of higher
      plants [Tanaka et al. (1996) Plant Cell Physiol. 37: 523]. A cDNA (MSODCc)
      encoding the cytosolic CuZn-SOD was isolated from cDNA library constructed from a
      liverwort cell suspension culture. The deduced amino acid sequence showed a
      higher degree of homology with the sequences of CuZn-SODs in chloroplasts than
      those in the cytosol of higher plants and an unique additional peptide in the C
      terminal region, but no plastid transit sequence. Northern blotting using MSODCc
      as a probe and immunoblot analysis with antiserum against the enzyme revealed
      that the steady state level of transcript was not affected by copper, but both
      CuZn-SOD protein and its activity increased.

PMID- 9559568
TI  - Historical exposure to inorganic mercury at the smelter works of Abbadia San
      Salvatore, Italy.
AB  - Metallic mercury production from cinnabar ore may result in high exposures to
      inorganic mercury, that are difficult to assess separately from the exposures
      originating from underground extraction, and previously have only been scantily
      described. We retrieved and analysed the air and biological mercury
      determinations on workers involved in the smelting process of the Abbadia San
      Salvatore mine (Monte Amiata, Italy). Native mercury was not present in the ore,
      and the exposure in the underground extraction was low. The smelter operated from
      1897 to 1983. Blood and urine (24/h urine collections and concentration samples)
      had been sampled in 1968 to 1982, and analysed for mercury by atomic absorption
      spectrophotometry, and relate to all subjects. Exposure to mercury in air had
      been determined in a small set of personal samples in 1982. The data relate to
      all jobs in the smelter process, and all jobs entailed substantial exposure to
      mercury. The overall distribution of breathing zone air, blood and urinary levels
      is right-skewed and similar to the log-normal distribution (air, median 48
      micrograms/m3, n = 49; blood, arithmetic mean AM 49 micrograms/L; geometric mean
      GM 26 micrograms/L, n = 192; urinary excretion, AM 140 micrograms/24 h, GM 78
      micrograms/24 h, n = 839; and urinary concentration, AM 160 micrograms/L, GM 83
      micrograms/L, n = 632). Air, blood and urinary values show a high ratio of the
      between- and within-job variance, indicating differences in exposure by job.
      Cinnabar pigment production, of which the exposure has not been characterised
      previously, was the job with the highest air (AM 160 micrograms/m3) and urinary
      levels (excretion AM 690 micrograms/24 h; concentration AM 1100 micrograms/L).
      Other jobs with high urinary levels were soot purification, laboratory work, and
      bottling. Cleaning of condensers showed the highest blood level (AM 280
      micrograms/L). There is a downwards time trend in mercury concentration in blood
      and in urine. The corresponding trend is not seen for urinary excretion levels,
      the reason for this being unclear. Roasters, which is the most frequently
      monitored group, show however a decreasing trend in all sets of data (e.g. the
      mean of urinary excretion decreased from 300 micrograms/24 h in 1968/69 to 50
      micrograms/24 h in 1980/81). The mercury exposure experienced by the smelters of
      Abbadia San Salvatore is in line with the few available data on workers from
      other mercury mines and smelters, and our data confirm the high exposure levels
      in this occupational group, in particular at cinnabar pigment production, soot
      purification, and condenser cleaning.

PMID- 9559569
TI  - Selecting an adequate respiratory protective device: the choice between a
      respirator and breathing apparatus.
AB  - An adequate respiratory protective device should keep the concentration of the
      pollutant inside the facepiece below the appropriate occupational exposure limit.
      Filtering respirators will not provide adequate protection if the device fails in
      an atmosphere which is immediately dangerous to life or health (IDLH). It has
      therefore been suggested that in contaminant concentrations above an IDLH level
      it is more appropriate to select breathing apparatus with an emergency breathing
      facility. In this paper IDLH levels published by the US National Institute of
      Occupational Safety and Health have been compared with UK occupational exposure
      limits. For some substances there was a relatively small difference between the
      IDLH level and the short-term occupational exposure limit (STEL). The median
      ratio of the IDLH level to the STEL was 10 for gases and vapours and 50 for
      aerosols. For almost half the substances with UK occupational exposure limits
      there is no IDLH value. It is concluded that the published IDLH concentrations
      are, on their own, an insufficient basis for selecting breathing apparatus over a
      filtering respirator. It is equally important to consider the likelihood that a
      filtering device may fail catastrophically since this determines the risk from
      wearing a respirator in an IDLH atmosphere. More emphasis should be placed on the
      control of potentially high exposure levels by means other than respiratory
      protection.

PMID- 9559570
TI  - Monitoring of occupational exposure to polycyclic aromatic hydrocarbons in a
      carbon-electrode manufacturing plant.
AB  - An investigation is presented of occupational exposure to polycyclic aromatic
      hydrocarbons (PAH) in a carbon-electrode manufacturing plant, as assessed by
      three monitoring methods, viz. environmental monitoring of the external dose by
      analysis of personal air samples, biological monitoring of the internal dose by
      analysis of urinary 1-hydroxypyrene (1-OHpyrene), and biological effect
      monitoring by dosimetry of PAH-DNA adducts in blood lymphocytes. On the basis of
      job conditions, workers at the plant were divided into three groups with presumed
      low, intermediate and high exposure to air-borne PAH, respectively. All air
      samples showed levels of total PAH below the current MAC-value in the
      Netherlands, which is 200 micrograms/m3, whereas the benzo[a]pyrene level was
      occasionally higher than the recommended concentration of 2 micrograms/m3. The
      values of 1-OHpyrene in urine from the intermediate and high exposure groups were
      significantly higher than those of the low exposure group, namely 3.6- and 8.2
      fold, respectively. Clear external and internal exposure was thus demonstrated
      for workers of the high and intermediate exposure groups, but this did not result
      in a measurable effect at the DNA level in blood lymphocytes. Tobacco smoking, on
      the other hand, caused a significant increase of the levels of PAH-DNA adducts
      but did not affect 1-OHpyrene values. These data suggest that smoking is a more
      important risk factor for adverse health effects, i.e. cancer, than occupational
      exposure to PAH in this plant.

PMID- 9559571
TI  - Individual-based and group-based occupational exposure assessment: some equations
      to evaluate different strategies.
AB  - Basically, two strategies can be considered for the analysis of hazardous
      pollutants in the work environment: group-based and individual-based strategies.
      This paper provides existing and recently derived equations for both strategies
      describing the influence of several factors on attenuation and on the standard
      error of an estimated linear regression coefficient relating a continuous
      exposure variable and a continuous health outcome via a simple linear regression
      model. We applied these equations using exposure variability information from
      industry-wide surveys over the past decade in order to gain more insight into the
      effects of various sources of exposure variability on choices among different
      analysis strategies. In general, for the modeling scenario considered here, there
      is not a straightforward criterion for choosing an optimal analysis strategy.
      Researchers have to decide between individual-based strategies generating
      precise, though biased, estimates or group-based strategies generating less
      precise but essentially unbiased estimates. For most exposure variability
      scenarios evaluated, an individual-based strategy yielded substantial
      attenuation. It is the authors' contention that the choice between individual
      based and group-based strategies should be based on validity, rather than on
      precision, of the estimated exposure-response coefficient.

PMID- 9559572
TI  - Temporary threshold shift of the vibration perception threshold following a short
      duration exposure to vibration.
AB  - The objective of this study is to analyze the evolution of the vibration
      perception threshold (VPT) following a short duration exposure to vibration. The
      literature reports experiments with 3 to 10 min exposure to vibration after which
      a steady state is not necessarily reached. The temporary threshold shift (TTS) of
      the VPT is extrapolated from data recorded during the recovery period. The
      assumption of a linear decrease with the logarithm of time gives erroneous
      results for the TTS extrapolated at the end of the exposure. 81 experiments were
      conducted on 9 young subjects without any neurological problem, exposed to
      acceleration amplitudes of 5, 20 and 80 ms-2 at frequencies of 31.5 (conditions 1
      to 3), 125 (conditions 4 to 6) and 500 Hz (conditions 7 to 9). The exposure to
      vibration lasted 32 min and was interrupted shortly at time 2, 4, 8, 16 to record
      the VPT at 31.5 and 125 Hz. The VPT was also recorded before the exposure and
      several times during the recovery. The evolution of the VPT appears to follow a
      first order model characterized by a maximum amplitude TTS, a time constant (tau)
      and a residual value (r, as a fraction of the TTS). The correlation coefficients
      between observed and predicted values in the 81 experiments are 0.881 at 31.5 Hz
      and 0.885 at 125 Hz. The TTS is influenced by the exposure amplitude and
      frequency and is different at the two test frequencies. It varies also
      significantly between the subjects and with their initial VPT value. The time
      constant is about 3 minutes at both test frequencies, while the residual fraction
      is of the order of 0.14 at 31.5 Hz and 0.07 at 125 Hz. Both parameters appear to
      be independent of the exposure parameters.

PMID- 9559573
TI  - Measurement and analysis of nicotine and other VOCs in indoor air as an indicator
      of passive smoking.
AB  - In Finland the Tobacco Act was amended in 1994 to include workplaces. The
      developed method for estimating passive smoking, or environmental tobacco smoke
      utilised the widely used measurement of volatile organic compounds in indoor air
      quality surveys. The method is based on active sorbent sampling, thermal
      desorption and gas chromatography/mass selective detection (GC/MS) analysis and
      it has been tested in a chamber and in field conditions. The method can be used
      simultaneously to measure volatile organic compounds and exposure to tobacco
      smoke. We recommend nicotine, collected by active sampling, as an indicator for
      the evaluation of the exposure to environmental tobacco smoke spreading from
      smoking areas.

PMID- 9559574
TI  - The effect of dust-protective respirator mask and the relevance of work category
      on urinary 1-hydroxypyrene concentration in PAH exposed electrode paste plant
      workers.
AB  - Large amounts of polycyclic-aromatic hydrocarbons (PAH) are found in the work
      environment of electrode paste workers. Inhalation and skin uptake are both
      important routes for PAH exposure. We have studied the effect of dust-protective
      respirator masks by measuring urinary 1-hydroxypyrene as a biomarker for PAH
      exposure. Eighteen workers divided into work categories at the factory were
      monitored by personal air sampling and urinary 1-hydroxypyrene every work shift
      for two consecutive weeks. In the second week of the study, the workers were
      encouraged to wear respirator masks persistently, which resulted in a significant
      reduction in urinary 1-hydroxypyrene in end-of-shift samples (paired t-test, P =
      0.009). When correcting urinary 1-hydroxypyrene for ambient air pyrene we found
      on average 41% reduction in urinary 1-hydroxypyrene concentration in the second
      week of the intervention study. There was a work-category dependent variation in
      the correlation between end-of-shift urinary 1-hydroxypyrene samples and pyrene
      measured in the breathing zone of the workers, most likely due to variable skin
      uptake of pyrene; the overall correlation coefficient was 0.26 (P = 0.015). The 1
      hydroxypyrene concentration in pre- and post-shift urine samples varied between
      0.7 and 69.6 mumol/mol creatinine in the normal work week, and depended on the
      work category. The particulate PAH exposure ranged from 0.6 to 21.4
      micrograms/m3. The ratio of particulate pyrene to benzo[a]pyrene varied from 1.6
      to 8.0 amongst the various work categories within the same plant. Multiple
      regression analysis showed that smoking and work day are explanatory variables
      for the concentration of 1-hydroxypyrene in urine. Thirty-nine percent of the
      variation in the urinary 1-hydroxypyrene level at the end of shift could be
      explained by the independent variables pyrene concentration in air, smoking
      habits, work day, use of respiratory mask, work category and age.

PMID- 9559575
TI  - Parallel dose-response curves in combination experiments.
AB  - A possible experimental design for combination experiments is to compare the dose
      response curve of a single agent with the corresponding curve of the same agent
      using either a fixed amount of a second one or a fixed dose ratio. No interaction
      is then often defined by a parallel shift of these curves. We have performed a
      systematic study for various types of dose-response relations both for the dose
      additivity (Loewe additivity) and for the independence (Bliss independence)
      criteria for defining zero interaction. Parallelism between dose-response curves
      of a single agent and those of the same agent in the presence of a fixed amount
      of another one is found for the Loewe-additivity criterion for linear dose
      response relations. For nonlinear relations, one has to differentiate between
      effect parallelism (parallel shift on the effect scale) and dose parallelism
      (parallel shift on the dose scale). In the case of Loewe additivity, zero
      interaction dose parallelism is found for power, Weibull, median-effect and
      logistic dose-response relations, given that special parameter relationships are
      fulfilled. The mechanistic model of competitive interaction exhibits dose
      parallelism but not effect parallelism for Loewe additivity. Bliss independence
      and Loewe additivity lead to identical results for exponential dose-response
      curves. This is the only case for which dose parallelism was found for Bliss
      independence. Parallelism between single-agent dose-response relations and Loewe
      additivity mixture relations is found for examples with a fixed dose-ratio
      design. However, this is again not a general property of the design adopted but
      holds only if special conditions are fulfilled. The comparison of combination
      dose-response curves with single-agent relations has to be performed taking into
      account both potency and shape parameters. The results of this analysis lead to
      the conclusion that parallelism between zero interaction combination and single
      agent dose-response relations is found only for special cases and cannot be used
      as a general criterion for defining zero-interaction in combined-action
      assessment even if the correct potency shift is taken into account.

PMID- 9559576
TI  - Extinction times and phase transitions for spatially structured closed epidemics.
AB  - This paper considers the time to extinction for a stochastic epidemic model of
      SEIR form without replacement of susceptibles. It first shows how previous
      rigorous results can be heuristically explained in terms of the more transparent
      dynamics of an approximating deterministic system. The model is then extended to
      include a host population structured into patches, with weak nearest-neighbour
      mixing of infection. It is shown, by considering the approximating deterministic
      system, that the expected time to extinction in a population of n + 1 patches
      each of size N is of the form a log N + bn, provided that N > Nc where Nc is a
      critical patch size below which transits are unlikely to occur. This corresponds
      to the simple decomposition of the time of an epidemic into the time it takes to
      spread through one patch plus the time it takes to transit to each of n
      successive patches. Expressions for this threshold and the coefficients of the
      time to extinction are given in terms of the transmission parameters of infection
      and the coupling strength between patches. These expressions are compared with
      numerical results using parameters relevant to a study of phocine distemper virus
      in North Sea seals, and the agreement is found to be good for large and small N.
      In the region when N approximately Nc, where transits may or may not occur,
      interesting transitional behaviour is seen, leading to a non-monotonicity of the
      extinction time as a function of N.

PMID- 9559577
TI  - Resonant population cycles in temporally fluctuating habitats.
AB  - Experiments with the flour beetle Tribolium have revealed that animal numbers
      were larger in cultures grown in a periodically fluctuating volume of medium than
      in cultures grown in a constant volume of the same average size. In this paper we
      derive and analyze a discrete stage-structured mathematical model that explains
      this phenomenon as a kind of resonance effect. Habitat volume is incorporated
      into the model by the assumption that all rates of cannibalism (larvae on eggs,
      adults on eggs and pupae) are inversely proportional to the volume of the culture
      medium. We tested this modeling assumption by conducting and statistically
      analyzing laboratory experiments. For parameter estimates derived from
      experimental data, our model indeed predicts, under certain circumstances, a
      larger (cycle-average) total population abundance when the habitat volume
      periodically fluctuates than when the habitat volume is held constant at the
      average volume. The model also correctly predicts certain phase relationships and
      transient dynamics observed in data. The analyses involve a thorough integration
      of mathematics, statistical methods, biological details and experimental data.

PMID- 9559578
TI  - Testing a model for the dynamics of actin structures with biological parameter
      values.
AB  - A simple mathematical model for the dynamics of network-bundle transitions in
      actin filaments has been previously proposed and some of its mathematical
      properties have been described. Other models in this class have since been
      considered and investigated mathematically. In this paper, we have made the first
      steps in connecting parameters in the model with biologically measurable
      quantities such as published values of rate constants for filament-crosslinker
      association. We describe how this connection was made, and give some preliminary
      numerical simulation results for the behavior of the model under biologically
      realistic parameter regimes. A key result is that filament length influences the
      bundle-network transition.

PMID- 9559579
TI  - The loss of immunity in directly transmitted infections modeling: effects on the
      epidemiological parameters.
AB  - When directly transmitted infectious diseases are modeled assuming an everlasting
      induced immunity (and constant contact rate), there are well-established formulas
      to deal with, which is not true if we include the loss of induced immunity. In
      general, the immunity induced by the disease is everlasting. We propose a model
      considering the loss of immunity and present methods for the estimation of two
      epidemiological parameters: the force of infection and the basic reproduction
      ratio. We also analyze the effects of the loss of immunity on these parameters.
      Based on these results, we concluded that reinfection can play an important role
      in highly vaccinated populations.

PMID- 9559580
TI  - Computational experiments support a competitive function in the CA3 region of the
      hippocampus.
AB  - The comprehension of activities and functions of complex brain structures
      requires, among other things, information on simultaneous activities in several
      regions. Results reported in the literature using multi(micro/macro)electrode
      recordings or imaging techniques provide incomplete information due either to the
      small size and/or small number of investigated regions or to the poor
      spatiotemporal resolution, respectively. This is particularly true for the
      hippocampus and its subfields, and mathematical modeling and computer simulation
      have been used with the aim of obtaining information when this is lacking. Global
      activities in the CA3 field of the hippocampus, and in particular the genesis of
      theta rhythm and sharp waves, have been investigated here by a mathematical model
      formulated within the frame of a kinetic theory of neural systems. The model has
      taken into account data of experimental results both on different PSPs recorded
      in hippocampal neurons and on recurrent pyramidal collateral geometries. The
      computational 'experiments' to which the model was subjected suggest that the
      sharp waves arise through a selective and short block of the fast inhibitory
      neurons of CA3, produced by a medial septum inhibitory input, whereas the theta
      activity is produced by a durable, continuous inhibition of the slow inhibitory
      neurons. Information obtained also suggests that the recurrent pyramidal
      collaterals subserve a competitive, rather than a cooperative, organization.
      Based on these results a hypothesis on the possible functional organization of
      the CA3 field and of the entire hippocampus has been formulated. According to
      this hypothesis, the CA3 imposes a serial order on the flow of activity arriving
      at the hippocampus from the entorhinal cortex and from its connected polymodal
      cortical regions. This ordering permits cortical activities, arriving at CA3 on
      appropriate time intervals, to produce effects in regions of brain to which the
      CA3 projects. The competing cortical activities are lost.

PMID- 9559581
TI  - Sulfonated chloroaluminum phthalocyanine incorporates into human plasma
      lipoproteins: photooxidation of low-density lipoproteins.
AB  - The interactions of sulfonated chloroaluminum phthalocyanine (AlPcSn) with human
      low-density lipoproteins (LDL) were studied in vitro in human plasma and in an
      isolated LDL fraction, in order to understand the potential effects of the
      sensitizer against LDL. The AlPcSn added to plasma distributes in all
      lipoproteins as observed by the drastic color changes of the separated fractions
      by ultracentrifugation. In isolated LDL, incubation with AlPcSn causes
      fluorescence quenching of the apoprotein tryptophan residues. Furthermore, AlPcSn
      incorporates in liposomes, with a lipid composition similar to the external
      monolayer of human LDL, as indicated by absorbance spectroscopy. The
      photosensitizing properties of AlPcSn in LDL particles were studied on the basis
      of the fluorescence quenching of previously incorporated cis-parinaric acid
      (PnA), used as an oxidation probe, and of O2 consumption. The photooxidation of
      either PnA or LDL lipids is highly dependent on irradiation time and on the dye
      concentration. Moreover, photooxidation of LDL proceeds only during the
      illumination period. After stopping the illumination and upon addition of Cu2+ to
      the LDL solution, the oxidative rate is resumed, probably due to hydroperoxide
      cleavage and formation of species able to propagate the oxidative reaction. Thus,
      our data indicate that AlPcSn distributes in human plasma lipoproteins and, in
      isolated LDL, it can interact either with the lipid phase or the apoprotein. The
      photooxidation of LDL induced by AlPcSn seems to involve singlet oxygen as the
      main reactive species in the degradative process.

PMID- 9559582
TI  - UV light-induced duplex-to-duplex crosslinking of DNA molecules in aqueous
      ethanol solutions.
AB  - Ultraviolet light is known to generate crosslinks between the complementary
      strands of DNA and between DNA and proteins. Here we demonstrate that the UV
      light also crosslinks DNA duplexes to other DNA duplexes. However, the duplex-to
      duplex crosslinks only appear in the presence of about 75% (vol/vol) ethanol plus
      a millimolar or submillimolar concentration of monovalent or divalent cations,
      e.g. 2 mM Na+. Methanol or formamide are ineffective. The present observations
      provide a direct means to detect physical contacts of DNA molecules or their
      parts, e.g. during recombination. It is remarkable that the solution conditions
      leading to the duplex-to-duplex UV light-induced crosslink formation are the same
      as those inducing the B-to-A conformational transition of DNA.

PMID- 9559583
TI  - Comparison of the time-resolved absorption and phosphorescence from the
      tryptophan triplet state in proteins in solution.
AB  - Measurement of the room temperature Trp triplet state lifetime in proteins by
      time-resolved phosphorescence can provide valuable information on the structure
      and dynamics of proteins in solution. Our time-resolved absorption measurements
      on the long-lived states resulting from electronic excitation of the chromophore
      demonstrate the presence of more complex behavior than revealed by time-resolved
      phosphorescence. To provide additional insight into this behavior, a comparative
      study of time-resolved transient absorption and time-resolved phosphorescence of
      proteins in solution was carried out. The results show that the time evolution of
      the long-lived states observed through transient absorption often differs
      considerably from that observed in time-resolved phosphorescence. In some
      proteins, the presence of competing reactions complicates the interpretation of
      the transient absorption measurements (which may affect the phosphorescence
      yield). A more complete characterization of these processes will likely prove
      useful in the study of protein structure and dynamics in solution.

PMID- 9559584
TI  - Fluoroquinolone antimicrobials: singlet oxygen, superoxide and phototoxicity.
AB  - The fluoroquinolone antibacterial agents possess photosensitizing properties that
      lead to phototoxic responses in both human and animal subjects. The phototoxicity
      order reported in humans is: fleroxacin > lomefloxacin, pefloxacin >>
      ciprofloxacin > enoxacin, norfloxacin and ofloxacin. Studies both in vivo and in
      vitro have related this phototoxicity to the generation of reactive oxygen
      species including hydrogen peroxide and the hydroxyl radical. We determined the
      quantum yields of singlet oxygen generation (phi delta) by detection of the
      singlet oxygen (1O2) luminescence at 1270 nm for several fluoroquinolones,
      naphthyridines and other structurally related compounds. All the fluoroquinolones
      examined have low phi delta values ranging from 0.06 to 0.09 in phosphate buffer
      at pD 7.5. We also determined the 1O2 quenching constants for these compounds and
      their values were on the order of 10(6) M-1 s-1, except for lomefloxacin whose
      rate constant was 1.8 x 10(7) M-1 s-1. The phi delta values were significantly
      decreased in a solvent of lower polarity such as methanol (0.007 < or = phi delta
      < or = 0.02). The production of 1O2 by these antibiotics did not correlate with
      the order reported for their phototoxicity. We also measured the photogeneration
      (lambda > 300 nm) of superoxide by these antibacterials in dimethylsulfoxide
      using electron paramagnetic resonance and the spin trap 5,5-dimethyl-1-pyrroline
      N-oxide. Although there is not a one-to-one correspondence between the relative
      rates of superoxide generation and the phototoxicity ranking of the
      fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a
      faster rate. Nevertheless, the magnitudes of the observed differences do not
      appear sufficient to explain the range of fluoroquinolone phototoxicity potencies
      in human and animal subjects in general and the high activity of fleroxacin and
      lomefloxacin in particular. For these latter drugs the photoinduced loss of the
      F8 atom as fluoride and the concomitant generation of a highly reactive carbene
      at C-8 provide a more plausible mechanism for their potent phototoxic and
      photocarcinogenic properties.

PMID- 9559585
TI  - Triplet photoreactivity of the diaryl ketone tiaprofenic acid and its
      decarboxylated photoproduct. Photobiological implications.
AB  - The 2-benzoylthiophene chromophore of the photosensitizing drug tiaprofenic acid
      and of its decarboxylated derivative is characterized by a unusually high energy
      gap between the T1 (pi, pi*) and T2 (n, pi*) excited states, which makes this a
      unique system to study the intrinsic photoreactivity of the two states. Weak
      fluorescence and phosporescence emission were detected at room temperature.
      Tiaprofenic acid undergoes photodecarboxylation from the triplet manifold as the
      main reaction. The photoprocess is temperature dependent with activation energy
      of 7-10 kcal/mol, close to the energy gap between T1 and T2. The decarboxylated
      product abstracts hydrogen in type I reactions. The involvement of T2 in the
      above processes is proposed. Moreover the decarboxylated derivative exhibits
      reactivity toward phenols, consistent with a participation of the T1 state as
      electron acceptor. The observed photoprocesses can account for biological
      photosensitization reactions, like membrane damage and protein modification.

PMID- 9559586
TI  - The induction and analysis of micronuclei and cell killing by ultraviolet-B
      radiation in human peripheral blood lymphocytes.
AB  - The DNA-damaging potential of ultraviolet-B (UVB) radiation was investigated by
      analyzing the frequency and origin of micronuclei (MN) in cytokinesis-blocked,
      binucleated (BN) peripheral blood lymphocytes (PBL) and cloning efficiencies (CE)
      of PBL after exposure to different fluences of UVB. In total, PBL obtained from
      five normal donors were investigated. The PBL from all donors showed a dose
      related, linear-quadratic increase in the frequency of MN per 1000 BN cells and
      in the frequency of micronucleated BN cells. In two experiments the origin of UVB
      induced MN was studied by analyzing MN for the presence or absence of centromeres
      by applying the MN assay in combination with a centromeric probe and fluorescence
      in situ hybridization. This revealed, for the first time, that UVB-induced MN
      were centromere negative, indicating that UVB acted exclusively as a clastogenic
      agent in the tested dose range. The PBL from all donors showed a clear dose
      dependent decrease in CE, after UVB exposure. The UVB-exposed PBL from all donors
      showed an inverse relationship between the induction of MN and the decrease in
      CE, but regression analysis revealed no correlation between the induction of MN
      and the decrease in cell survival. It is concluded that UVB has a clastogenic and
      cytotoxic effect on PBL.

PMID- 9559587
TI  - Ultraviolet B irradiation modulates the immune system of fish (Rutilus rutilus,
      Cyprinidae). I. Phagocytes.
AB  - Roach (Rutilus rutilus) were irradiated with a single dose of ultraviolet B (UVB)
      radiation (0.4 J/cm2) in order to study the effects of UVB on the nonspecific
      immune defense mechanisms of fish. Neutrophils and macrophages were isolated from
      the head kidney of fish on days 1-14 postirradiation. Both random and directed
      migration of neutrophils, studied by migration under agarose assay, were
      suppressed on day 1 after UVB irradiation. The respiratory burst of phorbol 12
      myristate 13-acetate-stimulated neutrophils and macrophages was also suppressed
      at days 1 and 2 after UVB irradiation. The suppression of migration and
      respiratory burst were restored or the responses were even enhanced later, but on
      the other hand spontaneous cytotoxicity of neutrophils toward 51chromium-labeled
      K562 target cells stayed suppressed throughout the 14 day follow-up. This study
      indicates that UVB radiation has the potential to suppress the functioning of
      phagocytes and to compromise the immune system of fish.

PMID- 9559588
TI  - Light regulation of phytochrome content in wild-type and aphototropic mutants of
      the moss Ceratodon purpureus.
AB  - In filaments of the moss Ceratodon purpureus, phototropism is controlled by the
      photoreceptor phytochrome. Thirty-three aphototropic mutants with a proposed
      defect in phytochrome-chromophore biosynthesis were isolated and analyzed. The
      phototropic response of those mutants was rescued with the precursor of the
      phytochrome chromophore, biliverdin. Phytochrome spectral activity was measured
      in 19 arbitrarily chosen mutants. All contained low but still measurable
      quantities of photoactive phytochrome; the highest level was around 15% of the
      wild-type. The level of total phytochrome (apophytochrome and holophytochrome) as
      assayed by immunoblotting was indistinguishable from wild-type. The content of
      photoactive phytochrome in Ceratodon is light-regulated. Phytochrome of wild-type
      kept for 24 h in red light was reduced to 50% as compared to dark controls but
      was unaffected by blue. The red-light-induced decrease was partially reversible
      by far-red light, indicating that phytochrome itself is the photoreceptor for
      this response. This regulation was further analyzed with the mutant ptr114, which
      contains 15% photoactive phytochrome as compared to the wild-type. In this
      mutant, continuous red light given for 6 days decreased the level of spectrally
      active phytochrome down to 25% of dark controls, whereas the amount of
      phytochrome found on immunoblots was hardly reduced. This indicates that the loss
      of phytochrome affects only the holoprotein and implies that Ceratodon
      phytochrome is specifically degraded as a far-red-absorbing phytochrome.

PMID- 9559589
TI  - Protection of UV-induced suppression of skin contact hypersensitivity: a common
      feature of flavonoids after oral administration?
AB  - In this study we investigated the effect of the dietary ingredients fruit and
      vegetable, green tea phenol extract (GTP) and the specific flavonoid components
      quercetin and chrysin on the UV-induced suppression of the contact
      hypersensitivity (CHS) response to picryl chloride (PCl). The SKH-1 mice were fed
      with test diet from 2 or 4 weeks before and during the UV irradiation (daily, 95
      mJ/cm2) and tested for the CHS ear-swelling response 10 weeks after the onset of
      the irradiation. For the CHS, mice were immunized with PCl by epicutaneous
      application on nonirradiated sites. Four days after sensitization all mice were
      challenged on both sides of each ear by topical application of one drop PCl. In
      addition, from mice fed with the fruit and vegetable mixture the number of
      Langerhans cells (LC) were scored in the skin and from mice fed with quercetin,
      quercetin levels in plasma were measured at week 11 after the start of UV
      irradiation. It was found that fruit and vegetable (19% in the diet), GTP (0.1%
      and 0.01% in the drinking water), quercetin (1% in the diet) and chrysin (1% and
      0.1% in the diet), prevented statistically significantly the UV-induced
      suppression of CHS to PCl. In the skin of mice fed with fruit and vegetables
      combined with UV irradiation the number of LC were comparable to the control
      mice, whereas the number of LC were significantly diminished in mice treated with
      UV only. This protective effect on the presence of LC in the epidermis after UV
      irradiation, which was also observed in a previous study with quercetin, may play
      a role in the prevention of UV-induced immunosuppression by the flavonoids
      tested. In conclusion, we found protection of flavonoids against UV-induced
      effects on CHS, which may be a common feature of most flavonoids.

PMID- 9559590
TI  - The effect of fluence rate on tumor and normal tissue responses to photodynamic
      therapy.
AB  - Photodynamic therapy (PDT), carried out at low fluence rates, may enhance tumor
      response as well as affect treatment selectivity. We have studied the effects of
      fluence rate on the response of the murine radiation-induced fibrosarcoma (RIF)
      to PDT using Photofrin (5 mg/kg). Tumor response was tested over a large range of
      fluence rates (10-200 mW/cm2) and fluences (25-378 J/cm2). Low fluence rates were
      more efficient; approximately 60 J/cm2 at 10 mW/cm2 was needed to achieve the
      same tumor growth delay as approximately 100 J/cm2 at 150 mW/cm2 and
      approximately 150 J/cm2 at 200 mW/cm2. Despite this increased efficiency, lower
      fluence rates still required longer treatment times for equivalent anti-tumor
      effects: 95 min for 57 J/cm2 at 10 mW/cm2 versus 11 min for 100 J/cm2 at 150
      mW/cm2. Effects of fluence rate on the PDT toxicity to normal tissue were
      examined through the response of the murine (C3H) foot to Photofrin PDT.
      Treatment with conditions that produced equivalent tumor responses, i.e. 57 J/cm2
      at 10 mW/cm2 and 100 J/cm2 at 150 mW/cm2, resulted in a more severe foot response
      at the higher fluence rate (median peak response: 0.9 at 10 mW/cm2, 1.5 at 150
      mW/cm2) with more time required for tissue to return to normal (8 days at 10
      mW/cm2, at least 30 days at 150 mW/cm2). However, when feet were treated with an
      equal fluence of 100 J/cm2 at various fluence rates, longer healing times
      accompanied the lower fluence rate treatments. Overall, this paper demonstrates
      that lower PDT fluence rates are associated with increased efficiency of tumor
      response. If this increased efficiency is accounted for by lowering treatment
      fluence, lower fluence rates also may result in a more favorable normal tissue
      response to treatment.

PMID- 9559591
TI  - Clinical trial networks: a unique opportunity for critical care.

PMID- 9559592
TI  - Corticosteroids in septic shock: resurrection of the last rites?

PMID- 9559593
TI  - Glucocorticoid treatment of sepsis and acute respiratory distress syndrome: time
      for a critical reappraisal.

PMID- 9559594
TI  - Survivors, beware of posttraumatic stress disorder: What shall we tell the Men in
      Black?

PMID- 9559595
TI  - Prophylactic granulocyte colony-stimulating factor in critically ill patients:
      not time yet.

PMID- 9559596
TI  - Inhibition of nitric oxide synthesis in sepsis: a promising strategy?

PMID- 9559597
TI  - Pneumocystis pneumonia in the intensive care unit: location, location, location?

PMID- 9559598
TI  - Unintended consequences.

PMID- 9559599
TI  - Tracheobronchography: old is not necessarily outdated--especially for the young.

PMID- 9559600
TI  - Reversal of late septic shock with supraphysiologic doses of hydrocortisone.
AB  - OBJECTIVES: Preliminary studies have suggested that low doses of corticosteroids
      might rapidly improve hemodynamics in late septic shock treated with
      catecholamines. We examined the effect of hydrocortisone on shock reversal,
      hemodynamics, and survival in this particular setting. DESIGN: Prospective,
      randomized, double-blind, placebo-controlled study. SETTING: Two intensive care
      units of a University hospital. PATIENTS: Forty-one patients with septic shock
      requiring catecholamine for >48 hrs. INTERVENTIONS: Patients were randomly
      assigned either hydrocortisone (100 mg i.v. three times daily for 5 days) or
      matching placebo. MEASUREMENTS AND MAIN RESULTS: Reversal of shock was defined by
      a stable systolic arterial pressure (>90 mm Hg) for > or =24 hrs without
      catecholamine or fluid infusion. Of the 22 hydrocortisone-treated patients and 19
      placebo-treated patients, 15 (68%) and 4 (21%) achieved 7-day shock reversal,
      respectively, a difference of 47% (95% confidence interval 17% to 77%; p = .007).
      Serial invasive hemodynamic measurements for 5 days did not show significant
      differences between both groups. At 28-day follow-up, reversal of shock was
      higher in the hydrocortisone group (p = .005). Crude 28-day mortality was 7 (32%)
      of 22 treated patients and 12 (63%) of 19 placebo patients, a difference of 31%
      (95% confidence interval 1% to 61%; p = .091). Shock reversal within 7 days after
      the onset of corticosteroid therapy was a very strong predictor of survival.
      There were no significant differences in outcome in responders and nonresponders
      to a short corticotropin test. The respective rates of gastrointestinal bleeding
      and secondary infections did not differ between both groups. CONCLUSIONS:
      Administration of modest doses of hydrocortisone in the setting of pressor
      dependent septic shock for a mean of >96 hrs resulted in a significant
      improvement in hemodynamics and a beneficial effect on survival. These beneficial
      effects do not appear related to adrenocortical insufficiency.

PMID- 9559601
TI  - Health-related quality of life and posttraumatic stress disorder in survivors of
      the acute respiratory distress syndrome.
AB  - OBJECTIVES: Despite considerable progress in intensive care management of the
      acute respiratory distress syndrome (ARDS), little is known about health-related
      quality of life in long-term survivors. In addition, intensive care treatment can
      be extremely stressful, and many survivors of ARDS report adverse experiences
      such as respiratory distress, anxiety, or pain during intensive care unit (ICU)
      treatment. This study was performed to assess health-related quality of life in
      survivors of ARDS and to test the hypothesis that adverse experiences during ICU
      treatment result in posttraumatic stress disorder (PTSD) and negative effects on
      health-related quality of life. DESIGN: Retrospective, cohort, case-controlled
      analyses. SETTING: A 12-bed multidisciplinary ICU of a tertiary care university
      hospital, capable of providing extracorporeal life support for adults with severe
      ARDS. PATIENTS: We studied 80 patients who were admitted to our hospital from
      1985 to 1995 and who survived an episode of ARDS. ARDS was defined according to
      the criteria of the American-European Consensus Conference on ARDS.
      INTERVENTIONS: Health-related quality of life was measured using the Health
      Status Questionnaire of the self-administered Medical Outcomes Study Short Form
      Survey that consists of 36 questions (SF-36) and the German version of the Post
      Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10), a self-report scale
      for the diagnosis of posttraumatic stress disorder based on the Diagnostic and
      Statistical Manual (Third Edition) criteria (American Psychiatric Association).
      The number of adverse experiences (anxiety, respiratory distress, pain, and
      nightmares) during intensive care was evaluated by means of a structured
      questionnaire. For each patient with ARDS, three age- and gender-comparable
      controls were randomly selected from databases providing normal values for the SF
      36 and PTSS-10 scores in populations at risk for posttraumatic stress disorder.
      MEASUREMENTS AND MAIN RESULTS: Survivors of ARDS showed statistically significant
      impairments in all eight health dimensions of the SF-36 when compared with normal
      controls (median reduction 21.3%, p < .006) with maximal impairments in physical
      function (median reduction 28.9%, p = .000) and a 38% higher frequency of chronic
      pain (p = .0001). Three of 34 patients reporting none, or one, adverse experience
      had evidence of posttraumatic stress disorder vs. 19 of 46 patients remembering
      multiple traumatic episodes (p = .007). Patients reporting multiple adverse
      experiences described the lowest health-related quality of life, with maximal
      impairments in psychosocial functioning (p < .005) and only small limitations in
      physical function. CONCLUSIONS: Long-term survivors of ARDS describe a good
      overall health-related quality of life. Major impairments in mental health
      domains of health-related quality of life are associated with the development of
      posttraumatic stress disorder and are a possible result of traumatic experiences
      during ICU therapy.

PMID- 9559602
TI  - Prolonged inhibition of nitric oxide synthesis in severe septic shock: a clinical
      study.
AB  - OBJECTIVES: Inhibitors of nitric oxide synthesis have been suggested to be of
      value in the treatment of hypotension during sepsis. However, earlier clinical
      reports only describe the initial effects of these nitric oxide inhibitors. This
      study was designed to examine the effects of the prolonged inhibition of nitric
      oxide synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) in patients
      with severe septic shock. DESIGN: Prospective, nonrandomized, clinical study.
      SETTING: Medical-surgical intensive care unit in a university hospital. PATIENTS:
      Eleven consecutive patients with ongoing hyperdynamic septic shock that was
      unresponsive to fluid resuscitation and vasopressor therapy. INTERVENTIONS:
      Measurements of hemodynamic, hematologic, and biochemical variables were made
      before, during, and after the start of a continuous intravenous infusion of 1
      mg/kg/hr of L-NAME, an inhibitor of nitric oxide synthesis, for a period of 12
      hrs. MEASUREMENTS AND MAIN RESULTS: Continuous infusion of L-NAME resulted in a
      direct increase in mean arterial pressure from 65 +/- 3 (SEM) to 93 +/- 4 mm Hg
      and an increase in systemic vascular resistance from 426 +/- 54 to 700 +/- 75
      dyne x sec/cm5, reaching a maximum at 0.5 hr. Pulmonary arterial pressure was
      increased from 31 +/- 2 to a maximum of 36 +/- 2 mm Hg at 1 hr, and pulmonary
      vascular resistance increased from 146 +/- 13 to a maximum of 210 +/- 23 dyne x
      sec/cm5 at 3 hrs. Paralleling these changes, cardiac output decreased from 10.8
      +/- 0.8 to 8.7 +/- 0.7 L/min and oxygen delivery decreased from 1600 +/- 160 to
      1370 +/- 130 mL/min (for all changes p < .05 as compared with the baseline
      value). Heart rate, cardiac filling pressures, oxygen consumption, urine
      production, arterial lactate concentration, and other biochemical parameters were
      not significantly changed by L-NAME administration (all p > .05). Arterial
      oxygenation was improved during L-NAME infusion, and the dosage of catecholamines
      could be reduced (both p< .05). Although sustained hemodynamic effects were seen,
      L-NAME was most effective during the early stages of administration, and the
      effect of L-NAME on blood pressure and vascular resistance tended to diminish
      throughout the continuous infusion of L-NAME. Seven of 11 patients ultimately
      died, with survival time ranging from 2 to 34 days. CONCLUSIONS: Nitric oxide
      appears to play a role in cardiovascular derangements during human sepsis. The
      increased blood pressure and vascular resistance values are sustained during
      prolonged inhibition of nitric oxide synthesis with L-NAME in patients with
      severe septic shock, although the hemodynamic changes are most significant in the
      early stages of L-NAME infusion. The high mortality rate in these patients may
      suggest that L-NAME has only limited effects on outcome.

PMID- 9559603
TI  - Variations in intensive care unit utilization for patients with human
      immunodeficiency virus-related Pneumocystis carinii pneumonia: importance of
      hospital characteristics and geographic location.
AB  - OBJECTIVE: To determine whether intensive care unit (ICU) use and outcomes for
      patients with human immunodeficiency virus (HIV)-related Pneumocystis carinii
      pneumonia vary by hospital characteristics and geographic location. DESIGN:
      Retrospective review of the medical records of 2,174 patients with HIV-related P.
      carinii pneumonia. SETTING: Random sample of 73 private, nine public, and 14
      Veterans Affairs hospitals in five cities (Chicago, New York, Los Angeles, Miami,
      and Durham, NC). PATIENTS: Stratified random sample of patients hospitalized with
      HIV-related P. carinii pneumonia from 1987 to 1990. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Among the 2,174 patients with P. carinii
      pneumonia, 398 (18%) patients received care in an ICU. ICU utilization varied
      significantly by patient and hospital characteristics, as well by as geographic
      location. Non-Hispanic whites, patients with Medicaid, and patients with a prior
      acquired immunodeficiency syndrome-defining illness were the least likely to
      receive care in an ICU. Patients in county- or state-owned hospitals and patients
      in hospitals with more P. carinii pneumonia-experience were also less likely to
      be cared for in an ICU. These differences in ICU utilization persisted when
      controlling for severity of illness, as well as other patient characteristics.
      Significant geographic variation in ICU utilization persisted after controlling
      for patient and hospital characteristics. Survival to hospital discharge after an
      ICU stay was significantly higher for patients without a prior acquired
      immunodeficiency syndrome-defining illness and for patients in hospitals with
      more P. carinii pneumonia experience. CONCLUSIONS: We found significant
      variations in ICU utilization by hospital characteristics and geographic location
      that remained significant after controlling for severity of illness and patient
      sociodemographic characteristics. Hospital and geographic variations in ICU
      utilization may make it difficult to generalize ICU outcomes across different
      hospitals.

PMID- 9559604
TI  - Acute withdrawal syndrome related to the administration of analgesic and sedative
      medications in adult intensive care unit patients.
AB  - OBJECTIVES: To estimate the frequency of acute withdrawal syndrome related to the
      administration of analgesic and sedative medications in mechanically ventilated
      adult intensive care unit (ICU) patients; to identify associated clinical
      factors. DESIGN: Retrospective review of medical records. SETTING: An adult
      trauma/surgical ICU in an urban Level I trauma center. PATIENTS: Twenty-eight
      mechanically ventilated adult trauma/ surgical ICU patients requiring >7 days of
      ICU care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily doses of all
      opioid, sedative, hypnotic, and major tranquilizer drugs administered to each
      patient were measured, as was duration of ICU stay, duration of mechanical
      ventilation, and duration of the administration of analgesic, sedative, and
      neuromuscular blocking agents (NMBAs) for each patient. All opioids and
      benzodiazepines were converted to their respective fentanyl and lorazepam
      equivalent units based on potency and bioavailability. Calculation of the weaning
      rate for each patient during tapering from opioid and benzodiazepine medications
      was performed. The presence or absence of acute withdrawal syndrome was
      identified for each patient. Nine (32.1%) patients developed acute withdrawal
      syndrome potentially related to the administration of analgesic or sedative
      medications. Patients in the withdrawal group received significantly higher mean
      daily (p = .049) and peak (p = .032) doses of fentanyl equivalents, as well as
      higher mean daily lorazepam equivalents (p = .049) compared with patients not
      experiencing withdrawal. Patients in the withdrawal group were also significantly
      more likely to have received neuromuscular blocking agents (p = .004) or propofol
      (p =.026) for >1 day during ICU admission compared with patients not experiencing
      withdrawal. Duration of mechanical ventilation (p = .049), benzodiazepine therapy
      (p = .048), and propofol therapy (p = .049) was also significantly longer in the
      group experiencing withdrawal. Withdrawal patients received a significantly lower
      mean daily dose of haloperidol (p = .026). There was a significant association
      between the development of withdrawal syndrome and the presence of ARDS (p =
      .017). Finally, the slopes of the lines representing opioid and benzodiazepine
      drug weaning were more steep for the withdrawal group, although these results did
      not achieve statistical significance. CONCLUSIONS: These results suggest that
      mechanically ventilated adult patients with extended ICU care (> or =7 days) who
      receive large doses of analgesic and sedative medications are at risk for acute
      withdrawal syndromes during drug weaning. The association between ARDS and
      withdrawal syndrome, combined with the observation that withdrawal syndromes were
      also associated with the use of neuromuscular blocking agents and prolonged
      mechanical ventilation, suggests that patients with ARDS may be more likely to
      receive high doses of analgesic and sedative medications, and are therefore at
      increased risk for withdrawal syndrome.

PMID- 9559606
TI  - How to use a review article: prophylactic endoscopic sclerotherapy for esophageal
      varices. Evidence Based Critical Care Medicine Group.
AB  - OBJECTIVE: To assess the validity of a meta-analysis about sclerotherapy for the
      primary prevention of bleeding from esophageal varices, to interpret the results,
      and discuss whether they apply in practice. DATA SOURCES: Critical appraisal
      techniques for systematic reviews. DATA EXTRACTION: Systematic reviews are
      distinct from narrative reviews in that they answer specific clinical questions,
      and have explicit and reproducible methods for searching, selecting, and
      appraising the primary studies, to create the most valid synthesis of the
      evidence. DATA SYNTHESIS: Meta-analyses are systematic reviews containing a
      critical appraisal and statistical summary of individual study results and their
      confidence limits, whereas qualitative systematic reviews provide a narrative
      executive summary of study results. CONCLUSIONS: High-quality systematic reviews
      are being used increasingly to guide practice, strengthening the link between
      research results and improved health outcomes. Understanding their strengths and
      limitations helps us to use them appropriately in practice.

PMID- 9559605
TI  - The 67gallium-transferrin pulmonary leak index in patients at risk for the acute
      respiratory distress syndrome.
AB  - OBJECTIVE: To determine the occurrence and clinical importance of increased
      pulmonary microvascular permeability in patients at risk for acute respiratory
      distress syndrome (ARDS). DESIGN: Prospective, cohort study. SETTING: Medical and
      surgical intensive care unit (ICU) and department of nuclear medicine of a
      university hospital. PATIENTS: Thirteen consecutive patients at risk for ARDS
      with sepsis (n = 4), multiple trauma (n = 3), hemorrhagic pancreatitis (n = 5),
      and near-drowning (n = 1), admitted into the ICU. All patients were intubated and
      mechanically ventilated in the course of the study. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The 67gallium-transferrin pulmonary leak index
      (PLI) (upper limit of normal in patients scheduled for major surgery 14.7 x 10(
      3)/min) was measured within 24 hrs of admission. In addition, radiographic, gas
      exchange, and ventilatory variables allowing calculation of the Lung Injury
      Score, were obtained on the day of the PLI (day 0) and from days 1 to 7. Patients
      were followed until discharge or death in the ICU. No patient developed ARDS
      (Lung Injury Score of >2.5 in the absence of congestive heart failure) and all
      but four patients survived. The PLI (median [range]) was 18.5 (7.0 to 81.9) x 10(
      3)/min and was supranormal in 8 of 13 patients (p < .001 vs. normal). The PLI
      correlated with the Simplified Acute Physiology Score (SAPS) II (r[s] = .79, p <
      .01) and was higher in nonsurvivors than in survivors (p < .05), with a tendency
      for a higher SAPS II in the nonsurvivors. On day 0, the chest radiographic score
      of alveolar abnormalities was 0 (0 to 4), indicating absence of radiographic
      abnormalities in most patients. Also, on day 0, the median PaO2/FIO2 ratio was
      257 (range 119 to 460). The Lung Injury Score on day 0 was 1.0 (0 to 2.0), which
      is consistent with mild acute lung injury in all but one patient. In the course
      of time, the oxygenation ratio was lower and the Lung Injury Score was higher in
      nonsurvivors than in survivors, particularly for the Lung Injury Score on days 1
      and 2. The PLI correlated directly with the Lung Injury Score on days 0 and 1. On
      day 0, the PLI correlated inversely with the oxygenation ratio. On the last
      evaluable day of the first ICU week, the PLI correlated directly with the Lung
      Injury Score and the positive end-expiratory pressure level. The duration of
      mechanical ventilation tended to be longer in patients with a supranormal PLI.
      CONCLUSIONS: In this small population, 61% of patients at risk for ARDS and with
      only mild respiratory changes exhibited increased microvascular permeability in
      the lungs at ICU admission. Increased permeability may be an early marker of
      acute lung injury and its clinical features, and may be associated with a
      relatively complicated respiratory course during the first week after admission,
      even in the absence of progression to ARDS. Finally, increased pulmonary
      microvascular permeability may be associated with severe underlying disease and
      ultimate mortality in the ICU.

PMID- 9559607
TI  - Effect of advance directives on the management of elderly critically ill
      patients.
AB  - OBJECTIVE: To evaluate the effects of advance directives on the management of
      elderly, critically ill patients. DESIGN: Retrospective chart review. SETTING:
      Teaching hospital medical/surgical, noncardiac intensive care unit (ICU).
      PATIENTS: The medical records of 401 patients, > or =65 yrs of age, admitted to
      the ICU between 1992 and 1995 were reviewed. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Advance directive statements included refusal of
      cardiopulmonary resuscitation (CPR), nutrition, intravenous medications,
      antibiotics, mechanical ventilation, and blood products. Nineteen (5%) patients
      had advance directives (study group). These patients were compared with 28 case
      matched (age, Acute Physiology and Chronic Health Evaluation II score, and
      diagnosis) critically ill patients without advance directives (control group). We
      compared the following data: cost per day; number of surgical procedures; number
      of radiographic studies; number of central venous and pulmonary artery catheter
      insertions; number of complete blood counts, electrolytes, and cultures sent for
      laboratory testing; number of days in the ICU/hospital; and mortality rates.
      Statistical analysis was performed using the Student's t-test for independent
      means and the chi-square equation. For all observed parameters, quantitative and
      dichotomous differences between study and control groups were not statistically
      significant. Two patients received CPR, despite advance directive statements
      refusing this treatment. CONCLUSIONS: Few critically ill seniors have advance
      directives. As assessed by objectively documented information, the level of care
      delivered to elderly ICU patients is not affected by the presence or absence of
      advance directive statements. Medical personnel need to be aware of whether or
      not patients have advance directive statements, as unauthorized CPR was
      administered to 11% of the patients who died with advance directives.

PMID- 9559608
TI  - Total plasma antioxidant capacity is not always decreased in sepsis.
AB  - OBJECTIVE: To compare total plasma antioxidant capacity and selected individual
      antioxidants in patients with varying degrees of severity of sepsis. DESIGN: A
      prospective, observational, consecutive case study. SETTING: A 16-bed intensive
      care unit (ICU) in a university teaching hospital. INTERVENTIONS: None. PATIENTS:
      Forty-six healthy controls, ten ICU patients, nine patients with systemic
      inflammatory response syndrome (SIRS), 11 septic patients, and 14 septic shock
      patients. Plasma was obtained in healthy patients scheduled for minor surgery
      immediately before anesthesia and in ICU patients within 24 hrs of admittance to
      the unit or diagnosis of SIRS, sepsis, or septic shock. MEASUREMENTS AND MAIN
      RESULTS: Using the total peroxyl radical trapping method, we found plasma
      antioxidant capacity to be lower in septic patients but higher in septic shock
      patients, as compared with controls. Bilirubin was the greatest contributor to
      the increase with shock, followed by uric acid. Neopterin also correlated with
      the peroxyl radical trapping antioxidant parameter values. CONCLUSION: Although
      total plasma antioxidant capacity is decreased from normal levels in septic
      patients, an increase in some oxidants contributes to an increased total
      antioxidant capacity in septic shock patients.

PMID- 9559609
TI  - Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary
      vascular mechanics and cardiac output in a pediatric swine model.
AB  - OBJECTIVES: In a pediatric swine model, the effects of increasing tidal volumes
      and the subsequent development of pulmonary overdistention on cardiopulmonary
      interactions were studied. The objective was to test the hypothesis that
      increasing tidal volumes adversely affect pulmonary vascular mechanics and
      cardiac output. An additional goal was to determine whether the effects of
      pulmonary overdistention are dependent on delivered tidal volume and/or positive
      end-expiratory pressure (PEEP, end-expiratory lung volume). DESIGN: Prospective,
      randomized, controlled laboratory trial. SETTING: University research laboratory.
      SUBJECTS: Eleven 4- to 6-wk-old swine, weighing 8 to 12 kg. INTERVENTIONS:
      Piglets with normal lungs were anesthetized, intubated, and paralyzed. After
      median sternotomy, pressure transducers were placed in the right ventricle,
      pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the
      pulmonary artery. MEASUREMENTS AND MAIN RESULTS: The swine were ventilated and
      data were collected with delivered tidal volumes of 10, 15, 20, and 25 mL/kg and
      PEEP settings of 5 and 10 cm H2O in a random order. Pulmonary overdistention was
      defined as a decrease in dynamic compliance of > or =20% when compared with a
      compliance measured at a baseline tidal volume of 10 mL/kg. At this baseline
      tidal volume, airway pressure-volume curves did not demonstrate pulmonary
      overdistention. Tidal volumes and airway pressures were measured by a
      pneumotachometer and the Pediatric Pulmonary Function Workstation. Inspiratory
      time (0.75 sec), FIO2 (0.3), and minute ventilation were held constant. We
      evaluated the pulmonary vascular and cardiac effects of the various tidal volume
      and PEEP settings by measuring pulmonary vascular resistance, pulmonary
      characteristic impedance, and cardiac output. When compared with a tidal volume
      of 10 mL/kg, a tidal volume of 20 mL/kg resulted in a significant decrease in
      dynamic compliance from 10.5 +/- 0.9 to 8.4 +/- 0.6 mL/cm H2O (p = .02) at a
      constant PEEP of 5 cm H2O. The decrease in dynamic compliance of 20% indicated
      the presence of pulmonary overdistention by definition. As the tidal volume was
      increased from 10 to 20 mL/kg, pulmonary vascular resistance (1351 +/- 94 vs.
      2266 +/- 233 dyne x sec/cm5; p = .004) and characteristic impedance (167 +/- 12
      vs. 219 +/- 22 dyne x sec/cm5; p = .02) significantly increased, while cardiac
      output significantly decreased (951 +/- 61 vs. 708 +/- 48 mL/min; p = .001). Each
      of these effects of pulmonary overdistention were further magnified when the
      tidal volume was increased to 25 mL/kg. The tidal volume-induced alterations in
      pulmonary vascular mechanics, characteristic impedance, and cardiac output
      occurred to a greater degree when the PEEP was increased to 10 cm H2O. Pulmonary
      vascular resistance and characteristic impedance were significantly increased and
      cardiac output significantly decreased for all tidal volumes studied at a PEEP of
      10 cm H2O as compared with 5 cm H2O. CONCLUSIONS: Increasing tidal volumes,
      increasing PEEP levels, and the development of pulmonary overdistention had
      detrimental effects on the cardiovascular system by increasing pulmonary vascular
      resistance and characteristic impedance while significantly decreasing cardiac
      output. Delivered tidal volumes of >15 mL/kg should be utilized cautiously.
      Careful monitoring of respiratory mechanics and cardiac function, especially in
      neonatal and pediatric patients, is warranted.

PMID- 9559610
TI  - Changes in the brain monoamine metabolism in acute liver failure produced by
      ischemia-reperfusion injury in rats.
AB  - OBJECTIVE: To investigate the relationship between behavioral alterations and
      changes in monoaminergic systems provoked by ischemia-reperfusion liver injury in
      rats. DESIGN: Prospective, randomized, controlled animal study. SETTING:
      University animal laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute
      liver failure was induced by occlusion of the left portal vein and the hepatic
      artery for 90 mins. Twenty animals were subjected to the behavioral examination.
      The brain water content was measured in 12 animals. Forty-two animals were used
      for the evaluation of brain monoamine turnover. Half of animals in each
      experiment were subjected to the ischemic operation. MEASUREMENTS AND MAIN
      RESULTS: A step-through passive avoidance test was used for the behavioral
      evaluation 48 hrs after the ischemic operation. Then, plasma concentrations of
      amino acids were determined. The brain water content was measured with the dry
      weight method. The brain monoamine turnover was evaluated by the depletion of
      norepinephrine and dopamine induced by alpha-methyl-p-tyrosine, or the
      accumulation of 5-hydroxyindoleacetic acid induced by probenecid. In the plasma
      analysis performed 48 hrs after the operation, marked damage was found in animals
      subjected to liver ischemia. Injured rats demonstrated impairment in the passive
      avoidance test. The plasma concentrations of branch-chain amino acids were
      decreased, and the plasma concentrations of aromatic amino acids were increased.
      However, the brain water content was not changed by liver ischemia. The turnover
      of both norepinephrine in the cerebral cortex and dopamine in the striatum was
      decreased. The turnover of 5-hydroxytryptamine in the cerebral cortex was
      increased markedly. CONCLUSION: In liver injury caused by liver ischemia, the
      excitatory neurotransmission by norepinephrine and dopamine is depressed and the
      inhibitory neurotransmission mediated by 5-hydroxytryptamine is facilitated,
      especially in the telencephalon.

PMID- 9559611
TI  - Prophylaxis against lipopolysaccharide-induced acute lung injury by alpha
      tocopherol liposomes.
AB  - OBJECTIVE: To investigate whether intravenously administered liposomal alpha
      tocopherol can protect the lung from the injurious action of Escherichia coli
      lipopolysaccharide (LPS). DESIGN: Prospective, randomized animal study. SETTING:
      Government research laboratory. SUBJECTS: Twenty adult male Sprague-Dawley rats.
      INTERVENTIONS: Animals were intravenously pretreated with alpha-tocopherol
      liposomes (20 mg alpha-tocopherol/kg body weight), plain liposomes, or saline.
      Twenty-four hours later, pretreated animals were challenged with an intravenous
      injection of LPS (E. coli 0111:B4, 1 mg/kg body weight), and killed 2 hrs after
      LPS challenge. MEASUREMENTS AND MAIN RESULTS: Challenge of saline-pretreated
      animals with LPS resulted in lung injuries as evidenced by an increase in wet
      lung weight and a reduction in pulmonary angiotensin converting enzyme (25%) and
      alkaline phosphatase (28%), injury markers of lung endothelial and epithelial
      type II cells, respectively. Also, LPS administration resulted in an increase in
      pulmonary myeloperoxidase and protease activities, indicative of a neutrophilic
      inflammatory response. Pretreatment of animals with liposomal alpha-tocopherol
      significantly attenuated the LPS-induced edematous lung weight response, and
      reduced the extent of injuries to the pulmonary endothelial and epithelial cells,
      demonstrated by a significantly smaller reduction in the corresponding enzyme
      marker activities. CONCLUSION: These results suggest that augmentation of the
      pulmonary antioxidant status can ameliorate LPS-induced lung injuries mediated by
      oxidative stress mechanisms.

PMID- 9559612
TI  - Effects of filter pore size on efficacy of continuous arteriovenous
      hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature
      swine.
AB  - OBJECTIVE: To evaluate the effect of hemofilter pore size on the efficacy of
      continuous arteriovenous hemofiltration (CAVH) in improving morbidity and
      mortality in an immature swine model of Staphylococcus aureus-induced septicemia.
      DESIGN: Prospective, randomized study with age-matched controls. SETTING:
      Biomedical research facility. SUBJECTS: Fourteen 4 to 8-wk-old, weaned Poland
      China swine, weighing 5 to 10 kg. INTERVENTIONS: Spontaneously breathing,
      ketamine-sedated swine (4 to 8 wks of age) were given an intravenous lethal dose
      of live S. aureus. Animals were then filtered with either a 50-kilodalton (kD)
      pore size filter (control) or a 100-kD pore size filter (experimental). No
      animals received antibiotics. MEASUREMENTS AND MAIN RESULTS: Physiologic,
      biochemical, and hematologic parameters were measured in all animals every 1 to 3
      hrs. Animals were monitored continuously and survival time (hr) was recorded
      (permanent survival = 168 hrs/7 days). Animals filtered with the 100-kD filter
      survived significantly longer than control animals (103 +/- 18 [SEM] vs. 56 +/- 9
      hrs). The 100-kD-filtered group had one permanent survivor (168 hrs). Protein
      concentration of the ultrafiltrate obtained from the 100-kD-filtered animals was
      eight-fold higher than control ultrafiltrate. The protein removed did not contain
      a high percentage of albumin (as determined by autoanalyzer methods). No
      significant differences were seen in any of the other measured parameters.
      CONCLUSIONS: CAVH significantly improved survival in swine with S. aureus-induced
      sepsis. The superior performance of the 100-kD filter vs. the 50-kD filter
      suggests that higher molecular weight mediators that are not removed efficiently
      by the 50-kD filter may be responsible for the morbidity and mortality seen in
      this model of sepsis. These mediators may be removed in greater proportion by our
      customized (100-kD pore size) filter.

PMID- 9559613
TI  - Right ventricular overload causes the decrease in cardiac output after nitric
      oxide synthesis inhibition in endotoxemia.
AB  - OBJECTIVE: To determine whether the decrease in cardiac output after nitric oxide
      synthase inhibition in endotoxemia is due to increased left ventricular afterload
      or right ventricular afterload. DESIGN: Prospective, randomized, unblinded study.
      SETTING: Research laboratory at an academic, university medical center. SUBJECTS:
      Nonanesthetized, sedated, mechanically ventilated pigs. INTERVENTIONS: Pigs were
      infused with 250 microg/kg of endotoxin over 30 mins. Normal saline was infused
      to maintain pulmonary artery occlusion pressure (PAOP) at a value not exceeding
      1.5 times the baseline value. Left ventricular dimensions and function were
      studied using echocardiography. Right ventricular volumes and ejection fraction
      were determined via a rapid thermistor pulmonary artery catheter. We also
      measured mean arterial pressure (MAP), cardiac output, pulmonary arterial
      pressure, and calculated pulmonary and systemic resistances. Gastric tonometry
      was used as an index of gastric mucosal oxygenation and peripheral oxygenation.
      When MAP had decreased to < or =60 mm Hg or had decreased 30 mm Hg from baseline,
      nine animals received NG-nitro-L-arginine methyl ester (L-NAME) at 15 mg/kg to
      restore MAP to baseline. A second group of animals (n = 6) continued to receive
      normal saline, ensuring that PAOP did not exceed 1.5 times its baseline value. A
      third group of pigs (n = 5) did not receive endotoxin and served as the time
      control. In this group, a balloon was used to occlude the descending thoracic
      aorta and to increase MAP by approximately the same amount as in the L-NAME
      group. MEASUREMENTS AND MAIN RESULTS: Endotoxin caused an increase in pulmonary
      arterial pressure and right ventricular volumes, and a decrease in gastric
      mucosal pH. Cardiac output was maintained in the animals receiving the saline
      infusion. By 2 hrs, pulmonary arterial pressure had decreased but was still
      notably higher than baseline. However, by this time, MAP had decreased to < or
      =60 mm Hg. L-NAME administration restored MAP to its baseline value but resulted
      in worsening pulmonary hypertension, increased right ventricular volumes, and
      decreased cardiac output, compared with the saline group. Three animals that
      received L-NAME died of right ventricular failure. We did not observe any
      evidence of left ventricular dysfunction with increased left ventricular
      afterload. Moreover, the restoration of MAP with L-NAME infusion did not correct
      gastric mucosal acidosis. No changes were noted in the time-control group.
      Occlusion of the thoracic aorta increased MAP but did not change cardiac output.
      This finding demonstrates that increases in left ventricular afterload of the
      magnitude seen with the infusion of L-NAME do not lead to decreases in cardiac
      output. CONCLUSION: The decrease in cardiac output after nitric oxide synthase
      inhibition in endotoxemia is due to increased right ventricular afterload and not
      to left ventricular afterload.

PMID- 9559615
TI  - Use of tracheobronchography as a diagnostic tool in ventilator-dependent infants.
AB  - OBJECTIVE: Comparison of investigations of the airway in ventilator-dependent
      infants. DESIGN: Consecutive infants with suspected upper airway abnormalities
      were investigated using rigid bronchoscopy and tracheobronchography. SETTING:
      Tertiary pediatric and neonatal intensive care units. PATIENTS: Eight infants
      with suspected airway abnormalities. INTERVENTIONS: Rigid bronchoscopy and
      tracheobronchography. MEASUREMENTS AND MAIN RESULTS: Structural abnormalities,
      segmental narrowing of the airways and the effect of various levels of positive
      end expiratory pressures on the narrowings were documented. In six of the eight
      cases, additional airway abnormalities were diagnosed with tracheobronchography
      compared with rigid bronchoscopy. CONCLUSIONS: In cases of suspected
      abnormalities of the upper airway in small infants unable to be weaned from
      ventilatory support, tracheobronchography may be a more reliable investigation
      method than rigid bronchoscopy. The ability to assess the structural and dynamic
      components of the airway accurately and safely allows a correct and long-term
      treatment plan to be established in this group of patients.

PMID- 9559614
TI  - Effect of prophylactic administration of recombinant human granulocyte colony
      stimulating factor (filgrastim) on the frequency of nosocomial infections in
      patients with acute traumatic brain injury or cerebral hemorrhage. The Filgrastim
      Study Group.
AB  - OBJECTIVE: To determine whether the use of prophylactic recombinant human
      granulocyte colony-stimulating factor (filgrastim) reduces the frequency of
      nosocomial infections in patients with either acute traumatic brain injury or
      cerebral hemorrhage. DESIGN: Randomized, placebo-controlled, double-blind,
      multicenter phase II study. SETTING: Intensive care units of seven medical
      centers. PATIENTS: Patients with either acute traumatic brain injury or cerebral
      hemorrhage who were intubated within 6 hrs of admission and who were expected to
      be ventilated for >72 hrs. INTERVENTIONS: Patients were randomized to receive
      daily subcutaneous injections of placebo (n = 21) or one of two doses of
      filgrastim (75 microg [n = 20] or 300 microg [n = 20]) for 10 days or until the
      absolute neutrophil count was >75,000 cells/mm3 or until extubation. MEASUREMENTS
      AND MAIN RESULTS: End points included increase in absolute neutrophil count,
      safety of filgrastim, and frequency of nosocomial infections (pneumonia,
      bacteremia, and urinary tract infection). Filgrastim caused a dose-dependent
      increase in absolute neutrophil count. There were no differences in the frequency
      of pneumonia or urinary tract infection; however, there was a dose-dependent
      decrease in the frequency of bacteremias (p < .05). Adverse events were similar
      among the three groups. There was one case of acute respiratory distress syndrome
      in the placebo group. CONCLUSION: In this patient population, use of filgrastim
      was safe and the agent appeared to reduce the risk of primary bacteremias but had
      no beneficial effects on mortality, length of stay, or other nosocomial
      infections.

PMID- 9559616
TI  - Accuracy of physiologic deadspace measurement in intubated pediatric patients
      using a metabolic monitor: comparison with the Douglas bag method.
AB  - OBJECTIVE: To evaluate the accuracy of physiologic deadspace (VD/VT) measurement,
      using a metabolic monitor. DESIGN: Prospective collection of data. SETTING:
      University-affiliated children's hospital with a 51-bed critical care area.
      PATIENTS: Infants and children who were sedated and paralyzed and were receiving
      mechanical ventilation through a cuffed endotracheal tube. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Mixed expired carbon dioxide tension (PECO2) was
      measured. With the Douglas bag method, mixed expired gas was collected over 15
      mins and was analyzed. With the metabolic monitor, FECO2 was measured for 15 mins
      and the results were averaged. The PECO2 was calculated by multiplying FECO2 by
      the barometric pressure. The PaCO2 was measured simultaneously. The PECO2 was
      corrected for the compressible volume in the ventilator circuit. All gas volumes
      were corrected for body temperature, pressure, and water vapor pressure. The
      physiologic deadspace/tidal volume ratio (VD/VT) was calculated for both
      techniques using the Enghoff modification of the Bohr equation. The accuracy of
      the VD/VT measured, by using the metabolic monitor, was assessed by comparing
      this measurement against the VD/VT measured by the Douglas bag method. This
      comparison was done by simple linear regression and correlation and by bias
      analysis (Bland and Altman method). The magnitude of compressible volume
      expressed as a fraction of the tidal volume delivered by the ventilator was
      compared with the error in VD/VT expressed as the difference between the
      uncorrected and corrected VD/VT. Sixteen paired measurements were made in 12
      children. The VD/VT measured by the metabolic monitor correlated well with the
      VD/VT measured by the Douglas bag method (r2 = .99; p < .0001). There was no
      correlation between the bias of VD/VT and the average VD/VT. As the magnitude of
      compressible volume increased, the error in VD/VT increased (r2 =.61; p < .001).
      CONCLUSIONS: The VD/VT can be measured reliably and accurately in intubated
      pediatric patients using a metabolic monitor. The metabolic monitor method is a
      convenient and simple alternative to the standard Douglas bag method.

PMID- 9559617
TI  - Programs, partnerships, and patient care: moving Society of Critical Care
      Medicine and critical care forward. The Presidential Address from the 27th
      Educational and Scientific Symposium of the Society of Critical Care Medicine.

PMID- 9559618
TI  - Prognosis in the intensive care unit: finding accurate and useful estimates for
      counseling patients.
AB  - OBJECTIVES: Counseling critically ill patients and their families about what the
      future is likely to hold requires accurate prognostic information. Our goal is to
      teach clinicians how to find and critically appraise prognostic studies that
      examine homogeneous populations. CLINICAL EXAMPLE: An article describing the
      outcomes of a group of children who are in a prolonged, persistent vegetative
      state. RECOMMENDATIONS: The validity of prognostic studies is increased when: a)
      the sample of patients is representative; b) patients are homogeneous with
      respect to prognostic risk; c) follow-up is sufficient to minimize the
      possibility that the missing patients could alter the interpretation of the
      results; and d) health outcomes are evaluated, using objective and unbiased
      criteria. The likelihood of these outcomes over time and the precision around
      these probability estimates should be easily understandable. Before using the
      results of these studies to counsel patients and families, practitioners should
      ensure that the patients in the study and their management are similar to the
      patient in question, and that follow-up of the subjects is sufficiently long.
      CONCLUSIONS: The criteria outlined in this article may assist clinicians in
      interpreting articles describing the prognosis of patients with similar clinical
      conditions.

PMID- 9559619
TI  - Understanding articles comparing outcomes among intensive care units to rate
      quality of care. Evidence Based Medicine in Critical Care Group.
AB  - OBJECTIVES: Comparisons of risk-adjusted outcomes among intensive care units
      (ICUs) is a relatively new but rapidly expanding area of ICU health services
      research. By investigating those factors that lead ICUs to have patient outcomes
      that differ from the average, the overall quality of care across ICUs may be
      improved. Our goal is to teach clinicians how to evaluate these types of
      articles. CLINICAL EXAMPLE: An article describing the development and application
      of an index used to assess the clinical performance and cost-effectiveness of 25
      ICUs. RECOMMENDATIONS: Valid comparisons of the outcomes among ICUs are made
      when: a) the outcome measures are accurate and comprehensive; b) the ICUs being
      compared serve similar patients; c) the sampling of patients is sufficient and
      unbiased; d) appropriate risk adjustment is undertaken by applying a valid model
      to reliably collected data; and e) the comparisons focus on care delivered in the
      ICU. To evaluate the results of the study, clinicians must evaluate how confident
      they are that the outcome differences being described are clinically important.
      Before changes in ICU policy are made based on these outcome differences, it is
      important to clarify which factors might have resulted in these extreme outcomes
      and whether these results are applicable in the ICU population that will see the
      impact of the changes. CONCLUSION: The potential for misinterpretation of outcome
      performance ratings may decrease if articles describing outcome differences are
      evaluated, using the criteria outlined in this article.

PMID- 9559620
TI  - Inhaled nitric oxide: technical aspects of administration and monitoring.
AB  - OBJECTIVES: Clinical applications of inhaled nitric oxide (NO) therapy resulted
      in the development of delivery systems and monitoring devices applicable to
      routine clinical care. This article presents the various components necessary for
      an adequate clinical use of inhaled NO, and discusses the NO gas mixture
      cylinders, inhaled NO delivery techniques and specifications, monitoring devices,
      and ending with an exhaustive description of the scavengers of nitrogen oxides
      (NOx). DATA SOURCES: Computerized search (CURRENT CONTENTS, MEDLINE) of published
      original research and review articles (approximately 200), conference abstracts
      and compendiums up to May 1997 (approximately 50), personal files, and contact
      with expert informants. STUDY SELECTION: Technical, experimental, and clinical
      reports were selected from the recent English, French, German, and Spanish
      literature, if pertinent to the administration or monitoring of inhaled NO. DATA
      EXTRACTION: The authors extracted all applicable data. DATA SYNTHESIS: The
      production of NO gas mixture cylinders must be certified with respect to gas
      purity, stability, and concentration (limits between 100 and 1000 ppm),
      guaranteed calibration, and specific color. An ideal inhaled NO delivery device
      requires a synchronized delivery, a minimal production of nitrogen dioxide (NO2),
      and should be simple to use (verification, calibration, convenient flushing,
      cylinder change possible while in use and a simple alarm setting) with full
      information (high and low alarms and available precision monitoring of NO, NO2,
      and O2). Emergency and transport systems must be readily available. The choice of
      the monitoring device (chemiluminescence or electrochemistry) should be made
      based on the knowledge of their strength and weakness for a particular clinical
      application. Finally, scavengers of NOx should be used with caution until
      specific filters are proven safe and effective. CONCLUSIONS: The great
      expectancies generated by inhaled NO action have led researchers to design
      personal inhaled NO delivery systems, but only with mitigated results. At
      present, medical companies are finding a financial interest in designing a
      delivery system which will suit the needs of clinicians and this, along with
      official governmental approval, will only then permit the use of inhaled NO
      safely and on a larger scale.

PMID- 9559621
TI  - Functional and ultrastructural evidence of myocardial stunning after acute carbon
      monoxide poisoning.
AB  - OBJECTIVE: To study human myocardial ultrastructural changes after carbon
      monoxide (CO) poisoning inducing reversible cardiac failure. DESIGN:  CASE
      REPORT: clinical, functional and morphologic findings. SETTINGS: Public
      university-affiliated hospital and electron microscopy laboratory. PATIENT: A 25
      yr-old woman with functional evidence of cardiac failure after acute CO
      poisoning. INTERVENTIONS: Hyperbaric and intensive care treatment over 10 days.
      Scintigraphic and cardiac angiography with endomyocardial biopsy. MEASUREMENTS
      AND MAIN RESULTS: Scintigraphy with 99mTc hexakis 2-methoxy-2-isobutyl isonitrile
      (sestaMIBI) showed an uptake defect in the left anterior descending artery
      territory. The cardiac angiography demonstrated a slight hypokinesis of the
      superior two thirds of the anterior wall and of the septal region with completely
      normal coronary angiograms. Electron microscopy of left ventricular biopsies
      showed slight ultrastructural changes in the myocytes. In addition, large
      glycogen deposits were mostly associated with swollen mitochondria. The patient
      was discharged in good clinical condition on day 10. CONCLUSIONS: Presence of
      glycogen deposits associated with abnormal mitochondria may be signs of the
      incapability of myocardial cells in utilizing energy substrata. In the presence
      of normal myocardial perfusion, our findings are consistent with the presence of
      a stunned myocardium-like syndrome. Early recognition and treatment of this
      clinical syndrome allow the prevention of myocardial infarction.

PMID- 9559622
TI  - Atrioventricular nodal reentrant tachycardia.

PMID- 9559623
TI  - Peripheral nerve stimulation and clinical assessment for dosing of neuromuscular
      blocking agents in critically ill patients.

PMID- 9559624
TI  - Abdominal incision tumor implantation following pneumoperitoneum laparoscopic
      procedure vs. standard open incision in a syngeneic rat model.
AB  - INTRODUCTION: A recent hamster model study suggests that the abdominal wall wound
      implantation rate increases following laparoscopic colon cancer surgery compared
      with the traditional open technique. However, results of that study were
      confounded by several factors, including a midline incision in the laparoscopy
      group, an unclear definition of wound implantation, significant age variations in
      study subjects, and cell line use with low viability. The aim of this study was
      to compare the abdominal incision implantation rates following a pneumoperitoneum
      laparoscopic-type procedure with a standard open incision using a syngeneic
      host/colon cancer rat model. METHODS: Viable DHD/K12 rat colon carcinoma cells (2
      x 10(5) cells/rat) were injected intraperitoneally via 18G angiocath into
      anesthetized, immunocompetent BD-IX rats (syngeneic host rats). Rats were then
      randomly divided into open incision and laparoscopy groups. At three weeks post
      operatively, tumor growth at the injection, incision, and port sites was
      measured. RESULTS: Following standard midline incision, 50 percent of rats (26/50
      rats) developed wound implantations, whereas only 25 percent of rats (14/57 rats)
      developed at least one trocar site wound implantation after laparoscopy with
      pneumoperitoneum. Fourteen percent of trocar sites (16/114 port sites) developed
      wound implantations. No tumor growth was noted on the peritoneal surfaces other
      than in the incisional sites. CONCLUSION: Laparoscopic-type procedure with
      pneumoperitoneum did not increase wound implantation in a syngeneic host/colon
      carcinoma rat model compared with the standard open incision technique.

PMID- 9559625
TI  - Incontinence after lateral internal sphincterotomy: anatomic and functional
      evaluation.
AB  - PURPOSE: This study was designed to evaluate the anatomic and functional
      consequences of lateral internal sphincterotomy in patients who developed anal
      incontinence and in matched controls. METHODS: The study includes 13 patients
      with anal incontinence after lateral internal sphincterotomy and 13 controls who
      underwent the same operation and were continent and satisfied with the results of
      the procedure. Patients underwent clinical evaluation, anorectal manometry,
      pudendal nerve terminal motor latency testing, and endoanal ultrasonography.
      RESULTS: Sphincterotomies were longer in incontinent patients (75 vs. 57
      percent), but the resting pressure and length of the high-pressure zone were not
      different between groups. Surprisingly, maximum voluntary contraction was higher
      in incontinent patients than in continent controls (136 vs. 100 mmHg). Rectal
      sensation and pudendal nerve terminal motor latency were similar in both groups.
      The defect in the internal sphincter was wider in incontinent patients than in
      continent controls (17.3 vs. 14.4 mm), but these differences were not
      statistically significant. The thickness of the internal sphincter measured by
      endoanal ultrasound was identical in both groups, but the external sphincter was
      thinner in incontinent patients both at the site of the sphincterotomy (6.8 vs.
      8.1 mm) and in the posterior midline (7.1 vs. 8.6 mm). CONCLUSIONS: Anal
      incontinence after lateral internal sphincterotomy is directly related to the
      length of the sphincterotomy. Whether secondary to preoperative sphincter
      abnormality or the result of lateral internal sphincterotomy, the external
      sphincter is thinner in incontinent patients than in continent controls.

PMID- 9559627
TI  - Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary
      nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer.
AB  - PURPOSE: The present study was designed to determine the frequency of germline
      mutations in the hMLH1 and hMSH2 genes in 31 families suspected of having
      hereditary nonpolyposis colorectal cancer who do not fulfill the criteria of the
      International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer
      but in whom a genetic basis for colon cancer is strongly suspected and 45
      patients with sporadic early-onset colorectal cancer who developed colorectal
      cancer before the age of 40 years without any family history of colorectal
      cancer. METHODS: Genomic DNAs were prepared from peripheral blood samples of
      patients who were tested. All coding exons and exon-intron borders of these two
      genes were screened, first with the polymerase chain reaction-single-strand
      conformation polymorphism method, followed by sequencing of the DNA fragments
      displaying an abnormal single-strand conformation polymorphism pattern. RESULTS:
      In 31 families with suspected hereditary nonpolyposis colorectal cancer, we found
      six different germline mutations in seven unrelated families, including one
      missense mutation and three frame-shift mutations in the hMLH1 gene and one
      missense mutation and one frame-shift mutation in the hMSH2 gene. Totally,
      frequency of mutation was 23 percent, 16 percent and 7 percent in the hMLH1 and
      hMSH2, respectively. Only one missense mutation of the hMSH2 gene was identified
      in 45 patients (2 percent) with sporadic early-onset colorectal cancer. The
      mutation detection rate in families with suspected hereditary nonpolyposis
      colorectal cancer was significantly higher than that of patients with sporadic
      early-onset colorectal cancer (P < 0.05). CONCLUSION: Our definition of suspected
      hereditary nonpolyposis colorectal cancer is useful in the diagnosis of
      hereditary nonpolyposis colorectal cancer and for identifying those families who
      need genetic presymptomatic diagnosis. Our results indicate that it may be
      important to perform DNA testing in families suspected of having hereditary
      nonpolyposis colorectal cancer. On the other hand, we only detected a low
      mutation rate (2 percent) in 45 patients with sporadic early-onset colorectal
      cancer.

PMID- 9559626
TI  - Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary
      nonpolyposis colorectal cancer kindreds and the general population.
AB  - PURPOSE: This clinical case review aimed to identify phenotypic variations in
      colorectal and extracolonic cancer expression between hereditary nonpolyposis
      colorectal cancer (HNPCC) families with MLH1 and MSH2 germline mutations and the
      general population. METHODS: Colorectal cancer onset and site distribution were
      compared among 67 members of MLH1 kindreds, 45 members of MSH2 kindreds, and
      1,189 patients from the general population. Synchronous and metachronous cancer
      rates, tumor stage, extracolonic cancer incidence, and survival were also
      compared. RESULTS: Mean ages of colorectal cancer onset were 44, 46, and 69 years
      for MLH1, MSH2, and the general population, respectively (P < 0.001). More
      proximal and fewer distal colon cancers were noted in HNPCC than the general
      population (P < 0.001, P = 0.04). Site distribution showed disparity of rectal
      cancers (8 percent MLH1 vs. 28 percent MSH2; P = 0.01) based on genotypes.
      Overall, synchronous colorectal cancer rates were 7.4, 6.7, and 2.4 percent for
      MLH1, MSH2, and the general population, respectively (P = 0.016). Annual
      metachronous colorectal cancer rates were 2.1, 1.7, and 0.33 percent for MLH1,
      MSH2, and the general population, respectively (P = 0.041). Colorectal cancer
      stage presentation was lower in HNPCC than the general population (P = 0.0028).
      Extracolonic cancers were noted in 33 percent of MSH2 patients, compared with 12
      percent of MLH1 patients and 7.3 percent of the general population with
      colorectal cancers (P < 0.001). Combined MLH1 and MSH2 ten-year survival was 68.7
      percent compared with 47.8 percent for the general population (P = 0.009 stage
      stratified, hazard ratio 0.57). CONCLUSION: The presence of rectal cancer should
      not preclude the diagnosis of HNPCC, because the incidence of rectal cancer in
      MSH2 was comparable with that in the general population. Phenotypic variations,
      including the preponderance of extracolonic cancers in MSH2 patients, did not
      result in survival differences between genotypic subgroups. These phenotypic
      features of HNPCC genotypes may have clinical significance in the design of
      specific screening, surveillance, and follow-up for affected individuals.

PMID- 9559628
TI  - Sphincter preservation with chemoradiation in anal canal carcinoma:
      abdominoperineal resection in selected cases?
AB  - PURPOSE: This study contained herein assessed long-term results, toxicity, and
      prognostic variables following combined modality therapy of patients with
      International Union Against (Cancer Classification T1-4, N0-3, M0 squamous-cell
      carcinoma of the anal canal. PATIENTS AND METHODS: Between 1985 and 1996, 62
      patients completed treatment with combined modality therapy. A median total dose
      of 50 Gy was given to the primary, perirectal, presacral, and inguinal nodes
      followed by a local boost in selected cases. 5-Fluorouracil was scheduled as a
      continuous infusion of 1,000 mg/m2 per 24 hours on days 1 to 5 and 29 to 33 and
      mitomycin C as a bolus of 10 mg/m2 on days 1 and 29. Routinely processed paraffin
      embedded sections were stained using monoclonal antibodies for detection of
      proliferating cell nuclear antigen and MIB1 (Ki-67) antigen to determine the
      labeling index. In addition, DNA ploidy was assessed after Feulgen staining.
      RESULTS: Actuarial cancer-related survival, no evidence of disease survival, and
      colostomy-free survival rates at five years were 81, 76, and 86 percent,
      respectively. In univariate analysis, T category (T1/2 vs. T3/4) was predictive
      for no evidence of disease survival (87 vs. 59 percent; P = 0.03) and colostomy
      free survival (94 vs. 73 percent; P = 0.05). N category (N0 vs. N1-3) influenced
      actuarial cancer-related survival (85 vs. 58 percent; P = 0.002) and no evidence
      of disease survival (80 vs. 53 percent; P = 0.02). A higher proliferative
      potential as measured by the MIB1 labeling index was associated with a better
      colostomy-free survival (90 vs. 50 percent; P = 0.04). In multivariate analysis,
      actuarial cancer-related survival was only influenced by the N category (P =
      0.03) and no evidence of disease survival by N category (P = 0.03) and mitomycin
      C dose (P = 0.04). Salvage abdominoperineal resection achieved long-term control
      in only four of seven patients with local failures. CONCLUSION: Treatment with a
      combination of radiotherapy and chemotherapy is safe and effective for patients
      with anal canal carcinoma. Abdominoperineal resection is indicated as a salvage
      procedure in nonresponding and recurrent lesions and may be of benefit in a small
      subgroup of patients with poor prognostic factors.

PMID- 9559629
TI  - Perioperative blood transfusions reduce long-term survival following surgery for
      colorectal cancer.
AB  - PURPOSE: The aim of the study contained herein was to investigate the association
      between blood transfusion and long-term outcome for patients treated for
      colorectal cancer, controlling for the effect of other prognostic factors. We
      also wanted to study whether blood storage time influenced the prognosis.
      METHODS: Cox's proportional hazards regression analysis was used to analyze data
      from 336 patients who survived resection with curative intent. Median follow-up
      was 5.8 (2-16.8) years or until death. RESULTS: Local recurrences and distant
      metastases were significantly more frequent when more than two units of blood had
      been transfused. In the multivariate Cox's analysis, with backward elimination of
      nonsignificant factors at the 10 percent level, the following risk factors were
      significantly related to death by colorectal cancer: tumor stage (T stage and N
      stage), perforation of tumor, age, and the need for a blood transfusion.
      Transfusions of more than two units of blood were independently and significantly
      associated with death from colorectal cancer (relative hazard, 2.7; 95 percent
      confidence intervals, 1.4-5.2). Time of blood storage had no effect on the
      prognoses. In patients dying from diseases unrelated to colorectal cancer, age
      and American Society of Anesthesiologists group were significantly related to
      death, whereas blood transfusion was not. CONCLUSION: We found an independent and
      significant association between perioperative blood transfusion and poor
      prognosis in colorectal cancer patients. Blood storage time was not a prognostic
      factor.

PMID- 9559630
TI  - Impaired interleukin-12 production is associated with a defective anti-tumor
      response in colorectal cancer.
AB  - INTRODUCTION: Despite development of many chemotherapeutic regimens, colorectal
      cancer continues to have a high mortality. One of the major new potential
      therapies is interleukin-12, a heterodimeric cytokine produced by antigen
      presenting cells. In vitro and in vivo studies have demonstrated the role of
      interleukin-12 in stimulating a cell-mediated anti-tumor response against a
      number of colon adenocarcinoma tumor models. However, it is unknown whether
      patients with colorectal cancer have impaired interleukin-12 production. A study
      was performed to investigate production of interleukin-12 preoperatively and the
      relationship between these levels and disease stage at surgery. METHODS:
      Preoperative peripheral blood mononuclear cells from colorectal cancer patients
      and age-matched controls were stimulated by Staphylococcus aureus Cowan's Strain
      1 (0.0075 percent wt/vol) in vitro for 24 hours. Expression of interleukin-12 was
      then assessed by enzyme-linked immunosorbent assay. A single pathologist assessed
      the tumors for stage according to TNM and Dukes classifications. RESULTS: Twenty
      eight patients with colorectal cancer and 14 controls were recruited for the
      study. Interleukin-12 production was significantly impaired in patients with
      colorectal cancer compared with controls (P = 0.014), especially those with
      advanced disease: Dukes C, P = 0.001 and T4, P < 0.05. CONCLUSION: Interleukin-12
      production is impaired in patients with colorectal cancer, especially those with
      advanced disease, suggesting a defective Thl-mediated anti-tumor response. These
      patients may well benefit from exogenous interleukin-12 treatment.

PMID- 9559631
TI  - Metronidazole may inhibit intestinal colonization with Clostridium difficile.
AB  - PURPOSE: Antibiotics suppress normal gut flora, allowing overgrowth of acquired
      or native Clostridium difficile, with release of toxins that cause mucosal
      inflammation. Oral metronidazole is used to treat antibiotic-associated colitis
      (pseudomembranous colitis). This study was designed to determine whether oral
      metronidazole, as part of preoperative bowel preparation, prevents or decreases
      incidence of antibiotic-associated colitis after elective colonic and rectal
      procedures. METHODS: Eighty-two patients (40 men) were prospectively, randomly
      assigned to receive one of two oral antibiotic regimens before colorectal
      surgery. All patients underwent mechanical bowel preparation with polyethylene
      glycol-electrolyte lavage solution before administration of oral antibiotics.
      Group 1 (n = 42) patients received three doses (1 g/dose) of neomycin and
      erythromycin. Group 2 (n = 40) patients received three doses (1 g/dose) of
      neomycin and metronidazole. Both groups received one preoperative and three
      postoperative doses of intravenous cefotetan (2 g/dose). Both groups had stool
      samples tested for C. difficile toxin in the preoperative and postoperative
      periods by enzyme-linked immunoabsorbent assay or by tissue culture cytotoxicity.
      Patients with preoperative stool studies positive for C. difficile were excluded
      from the study. RESULTS: Treatment groups were not different for age, gender, or
      surgical procedure. Mean age +/- 1 standard deviation was 67.6 +/- 13.6 (range,
      34-94) years in Group 1 and 62.1 +/- 13.5 (range, 35-84) years in Group 2 (P =
      0.069). Mean length of hospital stay +/- 1 standard deviation was 9.76 +/- 4.9
      (range, 4-28) days for Group 1 and 8.05 +/- 2.6 (range, 3-14) days for Group 2 (P
      = 0.053). Five patients in Group 1 (neomycin and erythromycin) and one patient in
      Group 2 (neomycin and metronidazole) had positive stool studies for C. difficile.
      Relative risk of colonization with C. difficile in Group 1 was 4.76 times that in
      Group 2 (95 percent confidence interval, 0.581, 39). This difference was not
      statistically significant (P = 0.202). There were no significant differences in
      C. difficile colonization rates with respect to age, length of stay, or gender.
      CONCLUSIONS: This study suggests that there may be a clinical association between
      use of metronidazole preoperatively and inhibition of intestinal colonization by
      C. difficile in this patient population undergoing colonic and rectal surgery.

PMID- 9559632
TI  - Bursting pressure in anastomotic healing in experimentally induced colitis in
      rats.
AB  - BACKGROUND: Experimental studies on healing of colonic anastomosis have been
      thoroughly investigated. However, clinical parameters of the healing process of
      anastomosis in the inflamed colon has not yet been reported. METHODS: In the
      present study, healing of anastomosis in trinitrobenzene-sulfonic acid-induced
      colitis in rats was assessed by measuring the bursting pressure and bursting wall
      tension. RESULTS: On postoperative day 4, bursting pressure and bursting wall
      tension were significantly lower (P < 0.001) in rats with colitis with or without
      anastomosis and normal colon with anastomosis, compared with normal colon without
      anastomosis. On postoperative day 7, bursting pressure and bursting wall tension
      of normal colon with anastomosis approached that of normal colon without
      anastomosis. However, bursting pressure and bursting wall tension of rats with
      colitis with or without anastomosis remained significantly lower (P < 0.001) than
      the latter. Furthermore, unlike rats without colitis in which perforation
      occurred mostly at the anastomotic line, the bursting site in colitic rats was
      predominantly away from the anastomotic line. CONCLUSIONS: These results suggest
      that in surgery for inflammatory bowel disease, it is the adjoining inflamed
      bowel wall that is vulnerable to be perforated in response to increasing
      intraluminal pressure rather than the anastomosis that is braced by the sutures.

PMID- 9559633
TI  - Rectal wall contractility in response to an evoked urge to defecate in patients
      with obstructed defecation.
AB  - PURPOSE: The aim of this study was to examine rectal sensory perception and
      rectal wall contractility in response to an evoked urge to defecate and to
      identify differences between control subjects and patients with obstructed
      defecation. METHODS: Twenty control patients (10 men; median age, 47 (range, 17
      78) years) and 29 female patients with disabling obstructed defecation (median
      age, 48 (range, 18-70) years) entered the study. Under radiologic control, an
      infinitely compliant barostat balloon was inserted over a guide wire into the
      proximal part of the rectum. Additionally, a latex balloon was introduced into
      the distal part of the rectum. This latex balloon was inflated until an urge to
      defecate was experienced. Simultaneously, rectal wall contractility was assessed
      by measuring the variations in barostat balloon volume. These variations were
      expressed as percentage changes from baseline volume. RESULTS: By comparing
      controls and patients with obstructed defecation, a significant difference was
      found regarding mean distending volume required to elicit an urge to defecate
      (135 +/- 38 vs. 214 +/- 87 ml of air; P < 0.001, Mann-Whitney U-test). In all
      controls, the evocation of an urge to defecate induced a pronounced increase in
      rectal tone, proximal to the distal stimulating balloon. By comparing controls
      and patients, the increase in rectal tone was found to be significantly higher in
      control subjects (35 +/- 10 vs. 9 +/- 10 percent; P < 0.001). Twenty-five
      patients (86 percent) showed no or only minimum (<20 percent) increase in rectal
      tone during the perception of an urge to defecate. In 14 of these patients, the
      threshold for this perception was increased. Only four patients (14 percent)
      showed a relatively normal increase (>20 percent) in rectal tone. However, their
      threshold for perception was greatly increased. CONCLUSION: The assembly used in
      this study provides a useful tool for investigation of rectal evacuation. In all
      of our patients, obstructed defecation was associated with abnormal rectal
      sensory perception and/or altered rectal wall contractility.

PMID- 9559634
TI  - Patterns of colonic motility as recorded by a sham fecaloma reveal differences
      among patients with idiopathic chronic constipation.
AB  - BACKGROUND: By using a technique designated sham fecaloma, we were able to
      identify two types of segmentary motor phenomenon: displacement motor phenomena
      and nondisplacement motor phenomena. The aim of the study contained herein was to
      evaluate for identification of patients with different types of slow-transit
      constipation. METHODS: Studies were performed in healthy subjects (n = 5; colonic
      transit time <30 hours) and in constipated patients (n = 6; colonic transit time
      >125 hours; normal rectoanal manometry). A Foley-type recording probe with two
      perfused catheters (proximal and distal) was used. A rigid sigmoidoscope was used
      to place the probe at the sigmoid colon. Values recorded by the distal catheter
      were subtracted (point by point) from the values recorded by the proximal
      catheter. Subtraction curves were analyzed to quantify characteristics of
      displacement motor phenomena (an anally directed pressure gradient) and
      nondisplacement motor phenomena (an orally directed pressure gradient). RESULTS:
      All healthy subjects had contractions during the recording session. Displacement
      motor phenomena were predominant (displacement motor phenomena/30 minutes = 21.2
      +/- 13.2; range, 3-39). Constipated patients yielded two different patterns:
      three patients had a very small number of contractions, and three patients had a
      prevalence of nondisplacement motor phenomena, with numbers similar to numbers of
      displacement motor phenomena in healthy subjects. A comparison of the patterns of
      constipated patients revealed a statistically significant difference (P = 0.039).
      CONCLUSION: Sham fecaloma is a simple and safe test. Constipated patients in this
      study had two different patterns of colonic motility: scarce activity without
      haustration and normal activity without displacement motor phenomena. This method
      might be useful as a diagnostic tool for clarification of the pathophysiology of
      severe colonic motor disorders.

PMID- 9559635
TI  - Experimental models of colorectal cancer.
AB  - PURPOSE: A review of in vivo and in vitro models of colorectal cancer is
      presented. METHODS: A retrospective literature review was performed with
      reference to CD-ROM Medline and Index Medicus. RESULTS: A comparison of the
      advantages and disadvantages of the models is presented in addition to a summary
      of individual model methodology and applications. CONCLUSIONS: Such models are a
      useful adjunct for surgical research in colorectal oncology.

PMID- 9559636
TI  - Observations on the treatment of painful cancer of the rectum, without
      obstruction, by establishing an anus in the left loin: with cases. 1811-1888.

PMID- 9559637
TI  - Foley catheter-assisted endoscopic treatment of severe anastomotic stenosis
      following anterior resection of the rectum.
AB  - Rectal stenosis following low anterior resection is common. Several methods of
      treatment have been described. We introduce a simple method for the treatment of
      anastomotic stenosis using a conventional proctoscope and an electric knife with
      a Foley catheter as an anvil. Under direct vision, this technique can afford
      accurate and safe incision of stenosis.

PMID- 9559638
TI  - Large aggressive angiomyxoma of the perineum and pelvis: an alternative approach.
      Report of a case.
AB  - Aggressive angiomyxomas are rare soft tissue tumors found mainly in the female
      reproductive mesenchyme and pelvis. They are low-grade sarcomas that have a
      propensity to recur locally. These tumors are encapsulated and have the same
      consistency as normal connective tissue, thus making wide excision difficult. We
      report a case of a large aggressive angiomyxoma in the perirectal tissues treated
      with preoperative angiographic embolization, causing ischemia of the tumor and,
      thus, improved visualization of the lesion. In addition, preoperative external
      beam irradiation and intraoperative electron beam radiotherapy were used to
      decrease the chances of local recurrence.

PMID- 9559639
TI  - Peutz-Jeghers syndrome manifesting complete intussusception of the appendix and
      associated with a focal cancer of the duodenum and a cystadenocarcinoma of the
      pancreas: report of a case.
AB  - The unusual occurrence of an "inside-out" appendix reported here is a case of
      complete intussusception of the appendix of a 45-year-old woman with Peutz
      Jeghers syndrome in whom the diagnosis of intussusception was made
      preoperatively. At laparotomy, the lead point of intussusceptum was revealed to
      be a Peutz-Jeghers syndrome polyp of the appendix. There was also a cystic lesion
      in the pancreas, and subsequent distal pancreatectomy revealed a
      cystadenocarcinoma of the pancreas. Two jejunal Peutz-Jeghers syndrome polyps and
      two duodenal Peutz-Jeghers syndrome polyps were found via intraoperative
      endoscopies. The duodenal polyps were endoscopically removed, whereas a jejunal
      wedge resection was performed for the adjoining jejunal polyps. One of the two
      duodenal polyps possessed an adenocarcinoma focus. To our knowledge, this is the
      first report of complete intussusception of the appendix caused by a Peutz
      Jeghers syndrome polyp.

PMID- 9559640
TI  - Pursestring mucosal closure after diverting stoma creation.

PMID- 9559641
TI  - Outcome following transanal endoscopic microsurgery.

PMID- 9559642
TI  - Advanced rectal cancer in a young pregnant Bedouin woman.

PMID- 9559643
TI  - Self-assessment quiz.

PMID- 9559644
TI  - High expression of uncoupling protein 2 in foetal liver.
AB  - To assess the putative role of mitochondrial uncoupling protein 2 (UCP2) during
      perinatal development, its expression was analysed in mice and rats. Expression
      was detected in a large range of foetal tissues. A unique developmental pattern
      of UCP2 expression was found in liver, where the level of UCP2 mRNA was about 30
      fold higher in foetuses than in adults (mice data), and started to decline
      immediately after birth. Neither UCP1 nor UCP3 mRNA was expressed in foetal
      liver. As in adult liver, immunohistochemical analysis suggested exclusive
      localisation of UCP2 in the monocyte/macrophage cells. Our results indicate a
      role of UCP2 in haematopoietic system development.

PMID- 9559645
TI  - Female sterility in mice lacking the basigin gene, which encodes a transmembrane
      glycoprotein belonging to the immunoglobulin superfamily.
AB  - Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin
      superfamily. Bsg knock-out mice exhibit infertility of both sexes. Based on
      limited results, defective implantation has been considered to be the cause of
      the female infertility. We demonstrate here that disruption of the Bsg gene
      produces the failure of female reproductive processes including not only
      implantation but also fertilization. Bsg mRNA expression in cumulus cells and
      basolateral localization of the Bsg protein in the endometrial epithelium further
      support the importance of Bsg in these processes.

PMID- 9559646
TI  - TRAF2 plays a dual role in NF-kappaB-dependent gene activation by mediating the
      TNF-induced activation of p38 MAPK and IkappaB kinase pathways.
AB  - We previously demonstrated that p38 MAPK is a crucial mediator in the NF-kappaB
      dependent gene activation induced by TNF. Here, we have studied the role of
      several TNF receptor-associated proteins and caspases in p38 MAPK activation by
      TNF. The latter appears to be dependent on TRAF2, but independent of FADD or
      caspases. Remarkably, p38 MAPK activation by TNF proceeds independently of the
      TRAF2-associated NF-kappaB-inducing kinase NIK, which is known to bind and
      activate two recently identified IkappaB kinases. These results demonstrate that
      two kinase pathways involved in NF-kappaB regulation, viz. NIK and p38 MAPK
      mediated, diverge at the level of TRAF2.

PMID- 9559647
TI  - Expression and regulation of phospholipase D in the human keratinocyte cell line
      HaCaT.
AB  - The generation of lipid second messengers via phosphatidylcholine (PC)-specific
      phospholipase D (PLD) has emerged as an important step leading to transduction of
      extracellular signals. In the present investigation the expression of human
      cytosolic PLD isoenzymes in the immortalized human keratinocyte cell line HaCat
      was determined. At the mRNA level we found the expression of hPLD1b and for the
      first time in human cells also the expression of hPLD2. For further analysis of
      enzyme expression at the protein level, hPLD1 peptide fragments were synthesized
      and specific antibodies were generated (rabbit) to be used for detection of hPLD1
      in Western blot experiments. Furthermore, small G-proteins were found to be
      involved in the regulation of PLD activity in HaCaT cells using the guanine
      nucleotide analogue GTPgammaS.

PMID- 9559648
TI  - Cloning, sequencing and expression of the genes encoding the sodium translocating
      N5-methyltetrahydromethanopterin : coenzyme M methyltransferase of the
      methylotrophic archaeon Methanosarcina mazei Go1.
AB  - The N5-methyltetrahydromethanopterin:coenzyme M methyltransferase of
      Methanosarcina mazei Go1 is a membrane-associated, corrinoid-containing protein
      that uses a transmethylation reaction to drive an energy-conserving sodium ion
      pump. The eight open reading frames encoding the eight different subunits of the
      methyltransferase were identified and sequenced. All of these subunits are shown
      to be heterologously expressed in minicells of the Escherichia coli mutant DK6.
      Sequence comparisons with the methyltransferases of thermophilic and
      hypothermophilic methanogenic archaea are presented. The participation of the
      gene product of mtrD in sodium ion translocation as well as a consensus sequence
      of a corrinoid binding motif in MtrA are discussed.

PMID- 9559649
TI  - Rapid and specific reactive oxygen species generation via NADPH oxidase
      activation during Fas-mediated apoptosis.
AB  - To determine Fas-induced reactive oxygen species (ROS) generation in cells
      sensitive to Fas-mediated apoptosis, chemiluminescence, a strong indicator of ROS
      generation, was monitored after stimulation with agonistic anti-Fas. Fas ligation
      resulted in a rapid and sustained ROS generation. The generation reached a
      maximum within 5 min and was still observed at least 40 min after the
      stimulation. No significant ROS generation was observed under conditions where
      apoptosis was absent. Furthermore, an NADPH oxidase inhibitor, diphenylene
      iodonium, prevented Fas-mediated ROS generation, suggesting that Fas induces ROS
      generation via stimulation of the oxidase system.

PMID- 9559650
TI  - Activation of the potato plant uncoupling mitochondrial protein inhibits reactive
      oxygen species generation by the respiratory chain.
AB  - A variety of plant tissues contain an uncoupling mitochondrial protein (PUMP),
      recently described and characterized by our group. In this study we show that the
      inhibition of PUMP activity in potato tuber mitochondria significantly increases
      mitochondrial H2O2 generation, while PUMP substrates, such as linoleic acid,
      reduce mitochondrial H2O2 generation. This H2O2 generation occurred mainly by the
      dismutation of superoxide radicals formed through monoelectronic reduction of O2
      by semiquinone forms of coenzyme Q. The results presented suggest that protection
      against mitochondrial oxidative stress may be a physiological role of PUMP.

PMID- 9559651
TI  - Atomic force microscopy examination of tobacco mosaic virus and virion RNA.
AB  - Atomic force microscopy (AFM) was applied to study uncoated virus particles and
      RNA prepared by stripping of tobacco mosaic virions (TMV) with mild alkali or
      urea and dimethylsulfoxide. We found that AFM is an appropriate method to study
      ribonucleoprotein and free RNA structures. Images of entire tobacco mosaic
      virions, partially uncoated TMV particles with protruding RNA molecule from one
      or both ends and individual RNA molecules are presented.

PMID- 9559652
TI  - Increase of local hydrogen ion gradient near bilayer lipid membrane under the
      conditions of catalysis of proton transfer across the interface.
AB  - The measurements of pH profiles in the unstirred layers (USLs) near planar
      bilayer lipid membranes (BLM) were applied for the evaluation of the hydrogen ion
      fluxes which were induced by nigericin in the presence of potassium ion
      gradients. It was shown that at high concentrations of KCl the increase in the
      concentration of citrate buffer caused an anomalous effect, namely, an increase
      in the local pH shifts in the USLs. The hydrogen ion flux rose 50 times upon the
      increase in the citrate concentration from 1 mM to 20 mM. Phosphate stimulated
      the flux 7 times under these conditions. In agreement with our previous results,
      at low KCl concentrations, when the process is limited by the K+-nigericin
      interaction, an increase in the buffer concentration led to a reduction of the
      local pH shifts, under these conditions the usual concentration dependence was
      observed. The data obtained favor the model implying the existence of the kinetic
      barrier for proton transfer at the membrane-water interface.

PMID- 9559653
TI  - Apolipoprotein E, transthyretin and actin in the CSF of Alzheimer's patients:
      relation with the senile plaques and cytoskeleton biochemistry.
AB  - We measured the levels of two beta-amyloid (Abeta)-sequestering proteins,
      apolipoprotein (Apo) E and transthyretin (TTR), in ventricular human
      cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients and controls in
      relation to brain histological findings. We also studied actin levels in CSF as a
      marker of the biochemical role of these two proteins in the cytoskeleton. We show
      that TTR levels in CSF were significantly decreased in AD patients compared to
      controls and negatively correlated with the senile plaque (SP) abundance.
      Moreover, actin levels were positively linked to TTR levels and increased in CSF
      samples of patients homozygous for the ApoE epsilon4-allele. We propose that TTR
      and ApoE4 may have competition in the aggregation of Abeta and its deposition in
      the SP of AD brain. The relationships between ApoE, TTR and actin could suggest a
      metabolic implication of ApoE genetics and TTR levels in cytoskeletal
      biochemistry which may be relevant to the pathogenesis of AD.

PMID- 9559654
TI  - X-ray and spectrophotometric studies of the binding of proflavin to the S1
      specificity pocket of human alpha-thrombin.
AB  - Proflavin can be used to study the interactions of inhibitors and substrates with
      thrombin by monitoring the changes in the visible absorption spectrum that occur
      on dye displacement. We have used microspectrophotometric methods to investigate
      the binding of proflavin to crystals of an alpha-thrombin-hirugen complex and
      have determined the structure by X-ray crystallography. The proflavin molecule
      binds in the S1 pocket of the enzyme with one of the amino groups hydrogen bonded
      to the carboxylate of Asp-189 while the protonated ring nitrogen is hydrogen
      bonded to the carbonyl of Gly-219. This result indicates that the proflavin
      displacement assay can be used to specifically monitor the binding of inhibitors
      to the S1 pocket.

PMID- 9559655
TI  - Solution conformation of an ET(B) selective agonist, ET
      1[Cys(Acm)1,15,Ala3,Leu7,Aib11], in CD3OH/H2O by 1H NMR and molecular modelling.
AB  - To understand the basic structural requirements for the biological activity of
      endothelin peptides, the solution structure of an ETB selective agonist, ET-1[Cys
      (Acm)1,15, Ala3,Leu7,Aib11, was investigated by 1H NMR spectroscopy and molecular
      modelling. The structure is characterised by an alpha-helical conformation
      between residues Ser5-His16 but is undefined at both the N and C termini. To
      date, neither the solution structures of linear modified peptides nor the effects
      of a methanol/water solvent system have been examined for endothelin or
      endothelin-like peptides. This structure plays an important role towards the
      design of endothelin receptor selective agonists and antagonists.

PMID- 9559656
TI  - Ectopic expression of Nramp1 in COS-1 cells modulates iron accumulation.
AB  - Nramp1 (natural resistance-associated macrophage protein) controls innate
      immunity and encodes a transporter of unknown function. Here we describe an
      antibody to Nramp1 displaying immunoreactivity towards a mature heavily
      glycosylated polypeptide of 90-100 kDa and a precursor form of 45 kDa in
      macrophages. Ectopic expression of the Nramp1 cDNA in COS-1 cells demonstrates
      that Nramp1 modulates cellular iron levels following loading with low molecular
      weight iron chelates. Surprisingly, Nramp1 does not enhance iron uptake, but
      expression is associated with reduced cellular iron loads. We propose Nramp1 may
      play a role in a salvage pathway of iron recycling.

PMID- 9559657
TI  - Contribution of NO synthases to neutrophil infiltration in the gastric mucosal
      lesions in rats with water immersion restraint stress.
AB  - A decrease in constitutive NO synthase (cNOS) activity and an increase in
      inducible NO synthase (iNOS) activity occurred with an increase in
      myeloperoxidase (MPO) activity, an index of neutrophil infiltration, in the
      gastric mucosa of rats with water immersion restraint (WIR) stress. This increase
      in gastric mucosal MPO activity was enhanced by pretreatment with NG-monomethyl L
      arginine, a non-selective NOS inhibitor, but was prevented with maintenance of
      gastric mucosal cNOS activity by pretreatment with aminoguanidine, a selective
      iNOS inhibitor. The MPO activity was negatively correlated with the cNOS activity
      in all WIR-stressed rats used (r=-0.723). These results suggest that a decrease
      in cNOS activity could contribute to an increase in neutrophil infiltration in
      the gastric mucosa of WIR-stressed rats.

PMID- 9559658
TI  - Substitution of Asn for Ser543 in the large fragment of Taq DNA polymerase
      increases the efficiency of synthesis of long DNA molecules.
AB  - Substitution of Asn for Ser543 in the large fragment of Taq DNA polymerase
      (Klentaq) increases several times the efficiency of synthesis of long (over 2
      kbp) DNA molecules. The difference in the DNA synthesis efficiencies by the
      mutant and native enzymes increased with the increase in the DNA fragment length.

PMID- 9559659
TI  - Plant profilin induces actin polymerization from actin : beta-thymosin complexes
      and competes directly with beta-thymosins and with negative co-operativity with
      DNase I for binding to actin.
AB  - Recombinant plant (birch) profilin was analyzed for its ability to promote actin
      polymerization from the actin:thymosin beta4 and beta9 complex. Depending on the
      nature of the divalent cation, recombinant plant (birch) profilin exhibited two
      different modes of interaction with actin, like mammalian profilin. In the
      presence of magnesium ions birch profilin promoted the polymerization of actin
      from A:Tbeta4. In contrast, in the presence of calcium but absence of magnesium
      ions birch profilin was unable to initiate the polymerization of actin from the
      complex with Tbeta4. However, under these conditions profilin formed a stable
      stoichiometric complex with skeletal muscle alpha-actin, as verified by its
      ability to increase the critical concentration of actin polymerization. Chemical
      cross-linking indicated that birch profilin competes with Tbeta4 for actin
      binding. Ternary complex formation of birch profilin with actin:DNase I complex
      was suggested by chemical cross-linking. However, the determination of the
      critical concentrations of actin polymerization in the simultaneous presence of
      birch profilin and DNase I indicated that profilin and DNase I did not form a
      ternary complex. These data indicated a negative co-operativity between the
      profilin and DNase I binding sites on actin.

PMID- 9559660
TI  - Effect of rutin and its copper complex on superoxide formation and lipid
      peroxidation in rat liver microsomes.
AB  - Two free radical scavengers, bioflavonoid rutin and the copper-rutin complex
      Cu(Rut)Cl2, inhibited lucigenin-amplified chemiluminescence and lipid
      peroxidation in rat liver microsomes, Cu(Rut)Cl2 being a 5-9 times more efficient
      inhibitor than rutin. The enhanced inhibitory activity of Cu(Rut)Cl2 was due to
      the presence of the additional superoxide-dismutating center (Cu), as follows
      from the comparison of its effects on microsomal chemiluminescence and cytochrome
      c reduction by xanthine oxidase. Similar effects of both inhibitors on superoxide
      production and lipid peroxidation as well as the elevated activity of Cu(Rut)Cl2
      indicate an important role of superoxide ion in the initiation of microsomal
      lipid peroxidation.

PMID- 9559661
TI  - Two high conductance channels of the mitochondrial inner membrane are independent
      of the human mitochondrial genome.
AB  - Patch-clamp techniques were used to characterize the channel activity of
      mitochondrial inner membranes of two human osteosarcoma cell lines: a
      mitochondrial genome-deficient (rho0) line and its corresponding parental (rho+)
      line. Previously, two high conductance channels, mitochondrial Centum picoSiemen
      (mCS) and multiple conductance channels (MCC), were detected in murine
      mitochondria. While MCC was assigned to the protein import in yeast mitochondria,
      the role of mCS is unknown. This study demonstrates that mCs and MCC activities
      from mouse mitochondria are indistinguishable from those of human mitochondria.
      The channel activities and their functional expression levels are not altered in
      cells lacking mtDNA. Hence, rho0 cells may provide a model system for elucidating
      the role of mitochondrial channels in disease processes and apoptosis.

PMID- 9559662
TI  - Molecular diversity of sterol 14alpha-demethylase substrates in plants, fungi and
      humans.
AB  - Metabolism of lanosterol (LAN), 24-methylene-24,25-dihydrolanosterol (24
      methyleneDHL), dihydrolanosterol (DHL) and obtusifoliol (OBT) by purified human,
      plant (Sorghum bicolor) and fungal (Candida albicans) sterol 14alpha-demethylase
      (CYP51; P450(14DM)) reconstituted with NADPH cytochrome P450 reductases was
      studied in order to elucidate the substrate specificity and sterol stereo- and
      regio-structural requirements for optimal CYP51 activity. Both human and C.
      albicans CYP51 could catalyse 14alpha-demethylation of each substrate with
      varying levels of activity, but having slightly higher activity for their
      respective endogenous substrates in vivo, dihydrolanosterol for human CYP51 (Vmax
      = 0.5 nmol/min/nmol CYP51) and 24-methylene-24,25-dihydrolanosterol for C.
      albicans CYP51 (Vmax = 0.3 nmol/min/nmol CYP51). In contrast, S. bicolor CYP51
      showed strict substrate specificity and selectivity towards its own endogenous
      substrate, obtusifoliol (Vmax = 5.5 nmol/min/nmol CYP51) and was inactive towards
      14alpha-demethylation of lanosterol, 24-methylene-24,25-dihydrolanosterol and
      dihydrolanosterol. These findings confirm that the presence of the 4beta-methyl
      group in the sterol molecule renders the plant CYP51 incapable of 14alpha
      demethylation thus revealing the strict active site conservation of plant CYP51
      during evolution.

PMID- 9559663
TI  - Inhibition of caspase activity induces a switch from apoptosis to necrosis.
AB  - The role of caspases in B lymphocyte cell death was investigated by using two
      broad spectrum inhibitors of the caspase family, Z-Asp-cmk and Z-VAD-fmk. They
      totally prevented spontaneous and drug-induced apoptosis and inhibited the
      CPP32/caspase-3-like activity exhibited by apoptotic cells. However, the
      suppression of apoptosis was not associated with a long-term increase of cell
      survival, but conversely, with a switch from apoptotic death to the necrotic
      form. These results strongly suggest that apoptosis and necrosis share common
      initiation pathways, the final issue being determined by the presence of an
      active caspase.

PMID- 9559664
TI  - Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve
      growth factor in differentiating PC12.
AB  - In PC12 sympathetic neurons activation and nuclear translocation of ERK family
      MAP kinases plays an essential role in processes underlying nerve growth factor
      (NGF)-dependent differentiation. We have recently cloned MKP-3 as a novel dual
      specificity phosphatase displaying selectivity towards inactivation of the ERK1
      and ERK2 MAP kinases. Here we report that in PC12 cells, MKP-3 undergoes powerful
      and specific up-regulation by NGF while a number of mitogens and cellular
      stresses are ineffective. NGF-stimulated MKP-3 expression appears after 1 h, is
      maximal at 3 h, and is sustained for 5 days. This coincides with a critical
      period of neurite outgrowth and terminal differentiation. Consistent with a role
      mediating inhibition of PC12 cell MAP kinases, NGF-stimulated ERK2 activation was
      suppressed considerably following pretreatment with fibroblast growth factor and
      9-cis-retinal, two additional differentiation factors found to induce powerfully
      MKP-3 expression. Given the clear cytosolic localization of MKP3 in PC12 cells
      and sympathetic neurons, these results suggest a critical role for inactivating
      ERK MAP kinases in non-nuclear compartments during essential stages of NGF
      mediated PC12 differentiation.

PMID- 9559665
TI  - Glucagon-like peptide-1 receptor expression in Xenopus oocytes stimulates
      inositol trisphosphate-dependent intracellular Ca2+ mobilization.
AB  - The signal transduction pathway of the cloned human glucagon-like peptide-1 (GLP
      1) receptor was studied in voltage-clamped Xenopus oocytes. Binding of GLP-1(7
      36)amide was associated with cAMP production, increased [Ca2+]i and activation of
      Ca2+-dependent Cl- current. The effect of GLP-1(7-36)amide reflects intracellular
      Ca2+ mobilization and was suppressed by injection of the Ca2+ chelator BAPTA and
      the inositol trisphosphate receptor antagonist heparin. The responses were not
      mimicked by the adenylate cyclase activator forskolin and unaffected by the
      protein kinase A (PKA) inhibitor Rp-cAMPS. We conclude that GLP-1 receptor
      expression in Xenopus oocytes evokes inositol trisphosphate-dependent
      intracellular Ca2+ mobilization independent of the cAMP/PKA signaling pathway.

PMID- 9559666
TI  - Loss of a consensus heparin binding site by alternative splicing of latent
      transforming growth factor-beta binding protein-1.
AB  - Latent transforming growth factor-beta binding protein-1 (LTBP-1), plays an
      important role in controlling localisation and activation of transforming growth
      factor-beta (TGF-beta). We show that alternative splicing generates a form of
      mRNA which lacks bases 1277-1435 (termed LTBP-1delta53). The 53 amino acids
      encoded by these bases include the eighth cysteine of the first cysteine repeat
      and a consensus heparin binding sequence. Sequencing of genomic clones showed
      that alternative splicing resulted from the use of an intra-exonic 3' splice
      acceptor site. The loss of the heparin binding site implies that LTBP-1delta53
      will bind to the extracellular matrix less efficiently than LTBP-1.

PMID- 9559667
TI  - Amino acid sequence, glycan structure, and proteolytic processing of the lectin
      of Vatairea macrocarpa seeds.
AB  - VML is a galactose-binding lectin isolated from Vatairea macrocarpa seeds. By SDS
      polyacrylamide gel electrophoresis, VML is a glycoprotein composed of a major 32
      34 kDa double band (alpha-chain) and minor 22 kDa and 13 kDa bands. N-terminal
      sequencing of electroblotted samples showed that the 22 and 13 kDa bands
      corresponded to C-(beta) and N-(gamma) terminal fragments of the alpha-chain,
      respectively. The primary structure of VML displays similarity with other
      leguminous lectins, particularly with Erythrina variegata, Robinia pseudoacacia
      and Sophora japonica lectins. VML is N-glycosylated at asparagine residues at
      positions 111 and 183 with one major glycan structure. Tandem mass spectrometry
      and methylation analysis indicated the presence of Manalpha1-6[(Manalpha1
      3)(Xylbeta1-2)]Manbeta1-4 -GlcNAcbeta1-4(Fucalpha1-3)GlcNAc, a typical plant
      Nglycan. Equilibrium sedimentation analysis by analytical centrifugation showed
      that VML had a mass of 122-130 kDa, which did not change within the pH range 2.5
      8.5. These data indicated that VML is a pH-independent homotetrameric protein and
      that a small proportion of the alpha-subunits is cleaved into noncovalently
      associated N- and C-terminal fragments. Mass spectrometric analysis suggested a
      mechanism for the proteolytic processing of VML. V. macrocarpa lectin contains a
      mixture of doubly (28,525 Da) and singly (27,354 Da) glycosylated alpha-chains.
      Deglycosylation of Asn-111 correlates with proteolytic cleavage of the Asn-114
      Lys-115 bond yielding glycosylated gamma (residues 1-114, 12,304 Da) and
      nonglycosylated beta-(residues 115-239, 14,957 Da) chains. Some beta-chain
      molecules are further deglycosylated and N-terminally processed yielding products
      of molecular masses of 13,783 Da and 13,670 Da.

PMID- 9559668
TI  - Phenobarbital induces cytochrome P4501A2 hnRNA, mRNA and protein in the liver of
      C57BL/6J wild type and aryl hydrocarbon receptor knock-out mice.
AB  - The aryl hydrocarbon receptor mediates the transcriptional response to a variety
      of hydrocarbons of members of the aryl hydrocarbon gene battery. Phenobarbital
      does not bind the aryl hydrocarbon receptor with high affinity but induces, in
      liver cells, expression of cytochrome P4501A. Using both wild type and aryl
      hydrocarbon receptor knock out C57BL/6J mice, we demonstrate that phenobarbital
      induced hnRNA, mRNA and protein for the cytochrome P-4501A2 gene in the presence
      or absence of the aryl hydrocarbon receptor. Using the DNA binding site for the
      aryl hydrocarbon receptor as a probe, gel retardation analyses showed that
      phenobarbital treatment induced protein binding, regardless of the presence of
      the aryl hydrocarbon receptor.

PMID- 9559669
TI  - Vanadate fully stimulates insulin receptor substrate-1 associated phosphatidyl
      inositol 3-kinase activity in adipocytes from young and old rats.
AB  - Vanadate stimulates adipocyte 2-deoxyglucose transport and GLUT-4 translocation
      to the membrane through an insulin receptor-independent but wortmannin
      inhibitable pathway. Vanadate stimulates PI 3-kinase in anti-IRS-1
      immunoprecipitates and the binding between IRS-1 and the p85alpha subunit of PI 3
      kinase. In insulin-resistant adipocytes from old rats vanadate fully stimulates
      IRS-1-associated PI 3-kinase, but partially activates glucose uptake. We conclude
      that: (a) vanadate stimulates 2-deoxyglucose uptake using a pathway that
      converges with that of insulin at the level of PI 3-kinase; and (b) adipocytes
      from old rats are defective in the insulin pathway at steps located both upstream
      and downstream of PI 3-kinase.

PMID- 9559670
TI  - cDNA cloning and mRNA distribution of a mouse very long-chain acyl-CoA
      synthetase.
AB  - The interaction of the adrenoleukodystrophy protein (ALDP), mutated in the
      peroxisomal disorder X-linked adrenoleukodystrophy, and the very long-chain acyl
      CoA synthetase (VLACS), the enzyme whose function is missing in this disease,
      remains obscure. As a first step to studying this interaction in wild type versus
      ALDP-deficient mice, we have cloned a VLACS cDNA from mouse liver. The 1860 bp
      open reading frame encodes a 620 amino acid protein with a predicted molecular
      mass of 70.3 kDa. By Northern blot analysis, a 2.6 kbp VLACS mRNA was highly
      abundant in liver and kidney and present at low levels in brain and testes. By RT
      PCR VLACS mRNA was also detected in heart and lung but remained undetectable in
      skeletal muscle and spleen. In contrast to the peroxisomal beta-oxidation marker
      acyl-CoA oxidase, whose mRNA level steadily increases during brain development,
      the VLACS transcript was found at a constant low level from embryo through
      adulthood, suggesting that additional isoforms may exist in brain.

PMID- 9559671
TI  - Structure, chromosome localization, and tissue distribution of the mouse twik K+
      channel gene.
AB  - We have recently discovered a new class of potassium channels with two pore
      forming domains and four membrane-spanning domains. When heterologously
      expressed, these channels produce time- and voltage-independent currents that
      classify them as background or leak channels. TWIK (for tandem of P domains in a
      weak inwardly rectifying K+ channel) was the first member of this family to be
      cloned. Here, we describe the genomic organization of TWIK in the mouse. The
      coding sequence as well as the untranslated sequences are contained in three
      exons. The twik gene (or KCNK1) has been mapped to chromosome 8, consistent with
      its localization to 1q42-43 in human. The twik gene is expressed in virtually all
      mouse tissues. It is most abundantly expressed in brain and moderately in other
      organs such as kidney. The level of expression is increased in brain and kidney
      from neonate to adult animals, but the TWIK message is also detected during
      embryogenesis, as early as day 7 post conception.

PMID- 9559672
TI  - The TRP Ca2+ channel assembled in a signaling complex by the PDZ domain protein
      INAD is phosphorylated through the interaction with protein kinase C (ePKC).
AB  - Photoreceptors which use a phospholipase C-mediated signal transduction cascade
      harbor a signaling complex in which the phospholipase Cbeta (PLCbeta), the light
      activated Ca2+ channel TRP, and an eye-specific protein kinase C (ePKC) are
      clustered by the PDZ domain protein INAD. Here we investigated the function of
      ePKC by cloning the Calliphora homolog of Drosophila ePKC, by precipitating the
      TRP signaling complex with anti-ePKC antibodies, and by performing
      phosphorylation assays in isolated signaling complexes and in intact
      photoreceptor cells. The deduced amino acid sequence of Calliphora ePKC comprises
      685 amino acids (MW = 78 036) and displays 80.4% sequence identity with
      Drosophila ePKC. Immunoprecipitations with anti-ePKC antibodies led to the
      coprecipitation of PLCbeta, TRP, INAD and ePKC but not of rhodopsin. Phorbolester
      and Ca2+-dependent protein phosphorylation revealed that, apart from the PDZ
      domain protein INAD, the Ca2+ channel TRP is a substrate of ePKC. TRP becomes
      phosphorylated in isolated signaling complexes. TRP phosphorylation in intact
      photoreceptor cells requires the presence of extracellular Ca2+ in micromolar
      concentrations. It is proposed that ePKC-mediated phosphorylation of TRP is part
      of a negative feedback loop which regulates Ca2+ influx through the TRP channel.

PMID- 9559673
TI  - Yeast putative transcription factors involved in salt tolerance.
AB  - Four putative yeast transcription factors (Hal6-9p) have been identified which
      upon overexpression in multicopy plasmids increase sodium and lithium tolerance.
      This effect is mediated, at least in part, by increased expression of the Enalp
      Na+/Li+ extrusion pump. Hal6p and Hal7p are bZIP proteins and their gene
      disruptions affected neither salt tolerance nor ENA1 expression. Hal8p and Hal9p
      are putative zinc fingers and their gene disruptions decreased both salt
      tolerance and ENA1 expression. Therefore, Hal8p and Hal9p, but not Hal6p and
      Hal7p, qualify as transcriptional activators of ENA1 under physiological
      conditions. Hal8p seems to mediate the calcineurin-dependent part of ENA1
      expression.

PMID- 9559674
TI  - Effective restoration of dystrophin-associated proteins in vivo by adenovirus
      mediated transfer of truncated dystrophin cDNAs.
AB  - A series of truncated dystrophin cDNAs (3.1-4.2 kbp) containing only three,
      three, two or one rod repeats with hinge 1 and 4 (named deltaDysAX2, AX11, AH3,
      M3, respectively) or no rod repeat retaining either hinge 1 or 4 (named
      deltaDysH1, H4, respectively) were constructed. These cDNAs were introduced into
      skeletal muscle of adult mdx mice using the adenovirus vector with a strong CAG
      promoter. deltaDysAX2, AX11, AH3 and deltaDysM3 expressed themselves successfully
      and recovered dystrophin-associated proteins effectively. Especially 3.7 kbp cDNA
      for deltaDysM3 offers the possibility of an approach utilizing newly developed
      virus vectors, such as an adeno-associated virus vector, toward gene therapy of
      Duchenne muscular dystrophy.

PMID- 9559675
TI  - Substitution of 5-methylcytosines for cytosines enhances the stability of
      topoisomerase I-DNA complexes and modulates the sequence selectivity of
      camptothecin-induced DNA cleavage.
AB  - We have investigated the binding and cleavage of DNA by human topoisomerase I
      using a 160 bp restriction fragment containing either natural bases or 5
      methylcytosine residues in place of cytosines. Experiments were performed in the
      presence and absence of the antitumour drug camptothecin which specifically
      inhibits topoisomerase I. Replacement of all cytosines with 5-methylcytosine
      residues (i) reinforces the enzyme-DNA interaction, (ii) enhances the stability
      of topoisomerase I-DNA complexes and (iii) modulates the sequence selectivity of
      camptothecin-induced DNA cleavage. The methyl group exposed in the major groove
      of the double helix is identified as a critical element for the interaction
      between topoisomerase I and DNA.

PMID- 9559676
TI  - Lipid membrane binding of NK-lysin.
AB  - The membrane-binding properties and pore-forming potential of the tumor-lysing
      and antibacterial polypeptide NK-lysin were investigated. Fluorescence quenching
      experiments show a drastic change of accessibility to Trp58 in solution and in
      association with a lipid membrane. Calcein release from large unilamellar
      vesicles and fluctuating conductivity observed across a planar lipid bilayer of
      asolectin show that NK-lysin renders lipid bilayers permeable in a transient
      fashion, indicating a nonspecific lipid interaction as the mechanism underlying
      the biological activity. FTIR experiments show the same amount and type of
      regular secondary structure of NK-lysin in the membrane as in aqueous solution
      and exclude a structural rearrangement into a set of parallel or antiparallel
      alpha-helices as the predominant conformation. The molecular mechanism of the
      membrane-destabilizing effect of NK-lysin is discussed.

PMID- 9559677
TI  - Further assignment of resonances in 1H NMR spectra of cerebrospinal fluid (CSF).
AB  - A number of previously unidentified 1H NMR signals detected in CSF spectra of
      patients with various neurological and metabolic diseases are assigned to
      metabolites, drugs and drug excipients. Two-dimensional 1H NMR spectroscopy (COSY
      and J-resolved) is employed to resolve resonances which are hidden by
      superimposed peaks in one-dimensional spectra. Assignments obtained by making use
      of 2-D techniques, and of a 1-D 1H NMR data base created for ca. 150 authentic
      compounds, enable us to clarify the nature of complex signal patterns found in
      crowded spectral regions of CSF such as the aliphatic methyl region at ca. 1.0
      ppm.

PMID- 9559678
TI  - A scheme for designating enzymes that hydrolyse the polysaccharides in the cell
      walls of plants.
AB  - A scheme is proposed for designating enzymes that hydrolyse the polysaccharides
      in the cell walls of plants. These enzymes are predominantly beta-1,4-glycanases.
      The scheme is based on the classification of the catalytic domains of glycoside
      hydrolases into families of related amino acid sequences. The new designation for
      an enzyme indicates its family and, because all members of a family have these
      characteristics in common, its three-dimensional fold and stereospecificity of
      hydrolysis. The scheme is intended to simplify comparison of the systems of
      enzymes produced by different microorganisms for the hydrolysis of plant cell
      walls.

PMID- 9559679
TI  - Conversion of Amadori product of Maillard reaction to Nepsilon
      (carboxymethyl)lysine in alkaline condition.
AB  - Nepsilon-(carboxymethyl)lysine (CML) is known to be formed by oxidative cleavage
      of Amadori products between C-2 and C-3 of the carbohydrate chain. We report here
      that CML formation from Amadori compounds is highly accelerated under alkaline
      conditions. Incubation of glycated human serum albumin (HSA) in 0.1 N NaOH led to
      the formation of CML whereas glycated HSA reduced by NaCNBH3 or non-glycated HSA
      did not generate CML. Nalpha-t-butyloxycarbonyl-Nepsilon-fructoselysine (Boc-FL),
      a model compound of Amadori product, was converted to CML under alkaline
      conditions. CML level of human sera (n=224) preincubated with 0.1 N NaOH
      correlated well with glycated albumin value (r=0.912) and hemoglobin A1c
      (r=0.797).

PMID- 9559680
TI  - The X-ray structure of a divergent cyclophilin from the nematode parasite Brugia
      malayi.
AB  - A structure of residues 1-177 of the cyclophilin domain of a large divergent
      cyclophilin from the filarial nematode parasite Brugia malayi has been
      crystallised and solved in two different crystal forms. The active site has a
      similar structure to that of human cyclophilin A. Two of the 13 residues
      important in forming the human cyclophilin A/cyclosporin A complex are altered in
      the B. malayi cyclophilin and explain the relatively poor inhibition of peptidyl
      prolyl isomerase activity by cyclosporin A.

PMID- 9559681
TI  - Human L-ficolin: plasma levels, sugar specificity, and assignment of its lectin
      activity to the fibrinogen-like (FBG) domain.
AB  - Ficolins are characterised by the presence of collagen-like and fibrinogen-like
      (FBG) sequences. Human L-ficolin is synthesised in the liver and secreted into
      blood circulation. In previous studies, it was shown to bind to N-acetyl-D
      glucosamine (GlcNAc). In the present study, its detailed sugar specificity and
      binding site have been investigated. It was found to bind to GlcNAc and GalNAc (N
      acetyl-D-galactosamine) while showing no significant affinity for the precursor
      sugars. The structure in these molecules which is recognised by L.-ficolin has
      been deduced to include an amide (-CO-NH-) or similar group. L-Ficolin was
      digested with collagenase and the collagenase resistant FBG domain was shown to
      bind to GlcNAc. Its levels in adult and cord blood-derived human plasma were also
      determined and showed that adult plasma contains approximately three times more L
      ficolin than that of newborn babies.

PMID- 9559682
TI  - A possible involvement of endogenous polyamines in the TNF-alpha cellular
      sensitivity.
AB  - A critical step in the cytotoxic action mechanism of tumor necrosis factor-alpha
      (TNF-alpha) involves, among mitochondrial dysfunctions, an early change of the
      inner membrane permeability displaying the characteristics of permeability
      transition. Cytosolic polyamines, especially spermine, are known to inhibit it.
      Our results show that spermine is only detectable in the TNF-alpha resistant C6
      cells while N1-acetylspermidine is present in the TNF-alpha sensitive WEHI-164
      cells, and putrescine and spermidine are found in both. TNF-alpha treatment does
      not change this distribution but only induces a quantitative alteration in TNF
      alpha sensitive cells. Omission of glutamine (energetic substrate) from the
      culture media alters neither the TNF-alpha responsiveness of both cell lines nor
      their polyamine distributions, only their quantitative polyamine contents.

PMID- 9559683
TI  - Cable grafting of the spinal accessory nerve after radical neck dissection.
AB  - BACKGROUND: From January 1981 through March 1996, 20 patients with head and neck
      cancer underwent radical neck dissection with sacrifice of the spinal accessory
      nerve and immediate reconstruction of the nerve using a microsurgical technique
      and a cable graft of the great auricular nerve. METHODS: Postoperative shoulder
      function was assessed via a subjective questionnaire, objective strength testing,
      and/or postoperative electromyography. The latter was used to evaluate for the
      presence and amplitude of voluntary motor potentials, the presence of
      fibrillation potentials, and nerve conduction latency. The group of patients who
      underwent cable grafting of the spinal accessory nerve was compared with a group
      of patients who underwent modified radical neck dissection with preservation of
      the spinal accessory nerve and with another group of patients who underwent a
      classic neck dissection with sacrifice of the spinal accessory nerve and no
      reconstruction. RESULTS: In terms of shoulder function, the group of patients in
      whom the spinal accessory nerve was reconstructed occupied an intermediate
      position; ie, their postoperative shoulder function was better than that of the
      patients who underwent radical neck dissection without reconstruction but not as
      good as that of the patients who underwent modified neck dissection with
      preservation of the spinal accessory nerve. CONCLUSION: Cable grafting of the
      spinal accessory nerve that has been sacrificed during radical neck dissection
      results in improved shoulder function in the postoperative period.

PMID- 9559684
TI  - Effect of pulsed electromagnetic stimulation on facial nerve regeneration.
AB  - OBJECTIVE: To determine if exposure to electromagnetic fields influences
      regeneration of the transected facial nerve in the rat. DESIGN AND METHODS: The
      left facial nerve was transected in the tympanic section of the fallopian canal
      in 24 rats randomly assigned to 2 groups. The cut ends of the facial nerve were
      reapproximated without sutures within the fallopian canal to maximize the
      potential for regeneration. Rats in the experimental group (n= 12) were then
      exposed to pulsed electromagnetic stimulation (0.4 millitesla at 120 Hz) for 4
      hours per day, 5 days per week, for 8 weeks. Rats in the control group (n=12)
      were handled in an identical manner without pulsed electromagnetic stimulation.
      Four other rats were given sham operations in which all surgical procedures were
      carried out except for the actual nerve transection. Two of these rats were
      placed in each group. Nerve regeneration was evaluated using electroneurography
      (compound action potentials), force of whisker and eyelid movements, and
      voluntary facial movements before and at 2-week intervals after transection.
      Histological evaluation was performed at 10 weeks after transection. Each
      dependent variable was analyzed using a 2-way analysis of variance with 1 between
      variable (groups) and 1 within repeated measures variable (days after
      transection). RESULTS: Statistical analysis indicated that N1 (the negative
      deflection of depolarization phase of the muscle and/or nerve fibers) area, N1
      amplitude, and N1 duration, as well as absolute amplitude of the compound action
      potentials, were all significantly greater 2 weeks after transection in the
      experimental than in the control group of rats. The force of eye and whisker
      movements after electrical stimulation was statistically greater in the
      experimental group of rats 4 weeks after transection. Voluntary eye movements in
      the experimental group were significantly better at 5 and 10 weeks, while whisker
      movements were better at 3 and 10 weeks. There was no statistical difference
      between the 2 groups for any histological variable. CONCLUSION: Results of this
      study indicate that pulsed electromagnetic stimulation enhances early
      regeneration of the transected facial nerve in rats.

PMID- 9559685
TI  - Laryngeal abductor reinnervation with a phrenic nerve transfer after a 9-month
      delay.
AB  - BACKGROUND: Successful restoration of laryngeal abductor function, using the
      phrenic nerve, has been described in the cat model in the acute phase. However,
      in clinical practice there is usually a considerable delay between injury to the
      RLN and presentation for treatment. Delayed reinnervation therefore would be more
      suitable in clinical practice. OBJECTIVE: To test the feasibility of delayed
      selective abductor reinnervation following transection of the recurrent laryngeal
      nerve (RLN). MATERIALS AND METHODS: In 12 cats, the right RLN was severed. Nine
      months later, the phrenic nerve was anastomosed to the distal RLN stump with all
      its branches directed toward the posterior cricoarytenoid muscle. For 10 weeks
      after the reconstruction, electromyography and videolaryngoscopy were performed
      weekly. Finally, histological analysis of the RLN was performed. RESULTS:
      Evaluation was possible in 11 cats. Reinnervation of the right posterior
      cricoarytenoid muscle with the phrenic nerve occurred in 10 cats following nerve
      anastomosis, but results of videolaryngoscopy showed adequate to good abduction
      in only 4 cats. The main limiting factor was reduced mobility of the
      cricoarytenoid joint. Evidence of spontaneous subclinical reinnervation after the
      delay was observed in 7 cats but apparently did not impede the surgical
      reinnervation. CONCLUSIONS: Delayed selective laryngeal abductor reinnervation
      was feasible, but function recovery was less successful than if performed
      immediately. Future investigations should concentrate on early determinants of
      spontaneous restoration of function to allow early selection of patients who are
      eligible for reinnervation surgery.

PMID- 9559686
TI  - Comparison of surgical complications after organ-preservation therapy in patients
      with stage III or IV squamous cell head and neck cancer.
AB  - OBJECTIVE: To determine the incidence of minor and major complications in
      patients with squamous cell carcinoma of the upper aerodigestive tract who
      require surgical salvage or planned neck dissection after an initial treatment
      regimen with radiotherapy or concurrent chemoradiotherapy for organ preservation.
      DESIGN: The medical records of 100 patients treated in a phase 3 trial comparing
      radiotherapy alone with concurrent chemoradiotherapy for stage III and IV head
      and neck squamous cell carcinoma were reviewed. Fifty-four patients underwent 59
      surgical procedures. Twenty-nine planned neck dissections were performed for
      persistent neck disease or initial stage N2 or greater. For persistent or
      recurrent disease at the primary site, 30 salvage operations were performed.
      SETTING: Academic tertiary care referral center. RESULTS: Complications occurred
      in 15 (46%) of the 33 procedures in the radiation-only group and 12 (46%) of the
      26 procedures in the chemoradiotherapy group. Major complications occurred in 4
      (12%) of the procedures in the radiation-only group and 3 (12%) of the procedures
      in the chemoradiotherapy group. The incidence of minor complications was 33% and
      35% in the radiation-only and chemoradiotherapy groups, respectively. The major
      complication rate for salvage operations did not differ between the radiation
      only and chemoradiotherapy groups (16% and 27%, respectively; P=.79 by chi2
      test). The incidence of major complications in planned neck dissections was 7% of
      the radiation-only group and 0% of the chemoradiotherapy group. CONCLUSIONS:
      After radiation or concurrent chemoradiotherapy, surgery can be performed with an
      acceptable rate of major complications. Adding chemotherapy did not increase the
      incidence of surgical complications. These results differ from other reports in
      the literature.

PMID- 9559687
TI  - Complications of microvascular head and neck surgery in the elderly.
AB  - OBJECTIVES: To evaluate the complications of head and neck reconstruction using
      microvascular free tissue transfers (MFTTs) performed in an elderly population
      and to determine whether these complications are more common than in a younger
      population. SETTING: Tertiary referral center. PATIENTS AND DESIGN:
      Retrospective, consecutive chart review of patients older than 70 years who
      underwent MFTT in the past 5 years (group 1). The complications in this
      population were compared with those in a second group (group 2) of consecutive
      patients younger than 70 years who were matched according to the site of the
      primary tumor. MAIN OUTCOME MEASURES: Surgical and medical complications.
      RESULTS: The median age for group 1 was 74 years and for group 2, 55 years. The
      overall complication rate for group 1 was 48%, compared with 57% for group 2. In
      group 1, surgical morbidity was less common and medical morbidity was more common
      than in group 2. Mortality rate was 6% for group 1 and 0% for group 2. The types
      of complications were similar for both groups. There was no difference in
      complication rates when complications were classified by site of the defect,
      patient status determined by American Society of Anesthesiologists
      classification, or use of preoperative radiation. The overall success rate of
      MFTT was 100% for group 1 and 94% for group 2. CONCLUSIONS: Microvascular free
      tissue transfers for head and neck reconstruction can be safely performed in the
      elderly. An age older than 70 years does not increase the rate of surgical
      complications following head and neck reconstruction with MFTT. Medical
      complications, however, are more common and are equally divided between
      bronchopulmonary and cardiovascular effects.

PMID- 9559688
TI  - The effects of more conservative neck dissections and radiotherapy on nodal
      yields from the neck.
AB  - OBJECTIVE: To determine the effects of conservative neck dissections (NDs) and
      preoperative radiotherapy on the quantitative recovery of lymph nodes from the
      neck. DESIGN: Retrospective review of case series. Data were obtained for age,
      preoperative TNM staging, type of ND, preoperative radiotherapy, total nodal
      yield (tNY), and positive nodal yield (pNY). The tNY and pNY were analyzed with
      factorial analysis of variance (ANOVA) to determine differences among types of ND
      and the effect of radiotherapy. SETTING: Tertiary care center for head and neck
      cancer. PATIENTS: Consecutive sample of 135 NDs in 110 patients with cancer of
      the head and neck. RESULTS: A significant difference in tNY was found among
      dissections (P<.001, ANOVA). Supraomohyoid ND had a significantly lower mean tNY
      (9.9 nodes) than both radical ND and modified radical ND (21.8 and 26.3 nodes,
      respectively; P<.05). Functional ND also had a significantly lower tNY (16.1
      nodes) than modified radical ND (P<.05); the differences between radical ND and
      both functional ND and modified radical ND were not statistically significant.
      Positive nodal yield was not different among the types of dissections (P=.62).
      Preoperative radiotherapy significantly decreased mean tNY from 22.0 to 17.1
      nodes (P=.02) over all types of dissections. Differences in tNY among dissection
      types were independent of the effect of radiotherapy. The presence or absence of
      preoperative radiotherapy had no significant effect on pNY (P=.18). CONCLUSIONS:
      Conservative modifications of the classic radical ND differ with respect to the
      quantity of cervical lymph nodes excised, but survival may not be altered since
      the pNY is not significantly different. When compared with the radical ND, the
      modified radical ND and functional ND do not compromise the quantity of cervical
      nodes excised. Radiotherapy significantly reduces the quantity of cervical nodes,
      but a significant number of nodes will still remain.

PMID- 9559689
TI  - Relationship between tympanic membrane perforations and retained ventilation
      tubes.
AB  - OBJECTIVES: To determine the effects of prolonged ventilation tube retention on
      tympanic membrane healing and the efficacy of patching procedures used
      concomitantly at the time of tube removal. DESIGN: Retrospective chart review.
      SETTING: Tertiary referral academic institution. PATIENTS: Seventy-six patients
      aged 12 years and younger, with a total of 99 ears identified from January 1989
      to December 1994. All patients underwent ventilation tube removal for prolonged
      tube retention or infection unresponsive to medical management. A minimum of 6
      months of follow-up was required for inclusion. INTERVENTION: Ventilation tube
      removal under general anesthesia, with or without concomitant patching. OUTCOME
      MEASURES: All medical charts were reviewed for age, sex, indications for tube
      removal, tube retention time, type of patch used (if any), type of tube, outcome
      after removal, other medical problems, and previous surgical history. RESULTS:
      The perforation rate was significantly higher in children with tubes retained
      beyond 36 months (P=.02). History of previous adenoidectomy predicted poor
      outcome, with a rate of 47% vs 17% in patients with no such history (P=.002).
      Patching did not improve healing. No other patient factors significantly
      influenced the perforation rate. CONCLUSIONS: Ventilation tube retention longer
      than 36 months resulted in an increased perforation rate after surgical removal.
      Paper patching at the time of tube removal does not improve healing. Prospective
      studies are needed to confirm these findings and to determine the efficacy of
      other patching techniques.

PMID- 9559690
TI  - Hearing loss due to myringotomy and tube placement and the role of preoperative
      audiograms.
AB  - BACKGROUND: Postoperative complications of myringotomy and tube placement often
      include otorrhea, tympanosclerosis, and tympanic membrane perforation. However,
      the incidence of sensorineural or conductive hearing loss has not been
      documented. Recent efforts to curb the use of preoperative audiometric testing
      requires documentation of this incidence. OBJECTIVE: To define the incidence of
      conductive and sensorineural hearing loss associated with myringotomy and tube
      placement. MATERIALS AND METHODS: A retrospective chart review of 550 patients
      undergoing myringotomy and tube placement was performed. A total of 520 patients
      undergoing 602 procedures (1204 ears), including myringotomy and tube placement,
      were assessed for preoperative and postoperative sensorineural and conductive
      hearing loss. RESULTS: No patient developed a postoperative sensorineural or
      conductive hearing loss. All patients resolved their conductive hearing loss
      after myringotomy and tube placement. There was a 1.3% incidence of preexisting
      sensorineural hearing loss. CONCLUSIONS: The incidence of sensorineural or
      conductive hearing loss after myringotomy and tube placement is negligible and
      the use of preoperative audiometric evaluation may be unnecessary in selected
      patients, but further studies need to be done to corroborate this small data set.

PMID- 9559691
TI  - The role of second-look nasal endoscopy after pediatric functional endoscopic
      sinus surgery.
AB  - OBJECTIVE: To determine if second-look nasal endoscopy (SLE) improves clinical
      outcome after pediatric functional endoscopic sinus surgery (FESS). DESIGN: A
      retrospective review was performed for all patients who had undergone FESS
      between January 1993 and December 1994. The patients were divided into 2 groups:
      those who underwent SLE 2 to 3 weeks after FESS (n=94) and those who did not
      undergo SLE after FESS (n=53). Patients with a history of cystic fibrosis, bone
      marrow transplantation, or isolated sphenoidal sinus disease were excluded from
      the study. SETTING: Pediatric tertiary care hospital. PATIENTS: All patients had
      a diagnosis of chronic rhinosinusitis, had failed medical therapy, and had
      subsequently undergone FESS. MAIN OUTCOME MEASURES: The need for revision sinus
      surgery was used as the definition for poor clinical outcome, indicating that
      sinus disease recurred or was persistent. The number of patients requiring
      revision sinus surgery in each group was compared. RESULTS: Revision surgery was
      performed in 20 of the 94 patients who underwent SLE after FESS. Revision surgery
      was performed in 10 of the 53 patients who did not undergo SLE after FESS. Six
      patients in the "no-second-look group" underwent follow-up nasal endoscopy at
      some time after the initial FESS. There was no significant difference in terms of
      clinical outcome between the 2 groups. CONCLUSIONS: The rate of revision sinus
      surgery was comparable in those patients who underwent SLE after FESS and those
      who did not. The usefulness and application of SLE need to be considered
      carefully.

PMID- 9559692
TI  - Interstitial Nd:YAG photocoagulation for vascular malformations and hemangiomas
      in childhood.
AB  - BACKGROUND: Vascular malformations and cavernous hemangiomas are common in
      childhood. Although cavernous hemangiomas may resolve spontaneously, aggressive
      intervention is required when their growth could damage vital adjacent
      structures, such as the orbit, nose, or tongue. OBJECTIVE: To evaluate the
      efficacy of interstitial Nd:YAG photocoagulation as an adjunct to intralesional
      and systemic corticosteroids for treatment of hemangiomas and vascular
      malformations that had failed to respond to other therapies. DESIGN: Prospective,
      nonrandomized trial. SETTING: Two referral practices of facial plastic and
      reconstructive surgery in tertiary care, academic medical centers. PATIENTS: Ten
      consecutive pediatric patients with either hemangioma or vascular malformation of
      the head and neck. INTERVENTION: Laser photocoagulation with an interstitial
      technique. The Nd:YAG fiber was introduced into the lesion via a 14-gauge
      angiocatheter needle, and the laser fiber was advanced as coagulation proceeded
      within the tissue. MAIN OUTCOME MEASURES: Decrease in the area of the target
      lesion, amount of energy applied, and number of treatments required to achieve
      reduction in size. RESULTS: Long-term follow-up demonstrated regression of the
      lesion in all 10 patients with good cosmetic results. The range of reduction in
      size was 20% to 98%. No reexpansion of the lesions was noted after a mean follow
      up of 13 months. CONCLUSIONS: Interstitial photocoagulation of hemangiomas and
      vascular malformations is an effective treatment for carefully selected patients.
      When properly applied, this technique can achieve reduction in the size of these
      lesions without compromising cosmesis.

PMID- 9559693
TI  - Serum level of placental growth hormone is raised in pregnancy rhinitis.
AB  - OBJECTIVE: To describe any relationship between pregnancy rhinitis and weight
      gain or serum levels of estradiol, progesterone, placental growth hormone, or
      insulinlike growth factor I. PATIENTS: Twenty-seven nonsmoking healthy pregnant
      women aged 22 to 38 years (mean age, 28 years) who had no history of respiratory
      allergy or chronic nasal or sinus problems volunteered to enter the study. They
      had no nasal complaints at entry. METHODS: Nasal patency was registered daily
      from early pregnancy until 1 month after delivery. Nasal and oral peak expiratory
      flow rates were established, and the subjective blockage was scored from 0 to 4,
      with 0 indicating no blockage. Serum samples were collected and weight was
      measured on 4 occasions during pregnancy and again at the end of the study.
      Pregnancy rhinitis was diagnosed if the subjective nasal obstruction score was 1
      or higher every morning for at least 6 weeks immediately preceding delivery, then
      returned to 0 within 2 weeks and remained at 0 until the end of the study. If on
      any day other signs of respiratory tract infection occurred, that day was
      excluded. RESULTS: Pregnancy rhinitis was diagnosed in 5 women. These 5 women
      showed significantly higher levels of placental growth hormone than the women
      without the diagnosis. No significant difference was found between the 2 groups
      regarding body weight or any of the other serum levels studied. CONCLUSIONS:
      Serum level of placental growth hormone is raised in pregnancy rhinitis and may
      be involved in its pathogeny. Pregnancy rhinitis does not significantly raise
      weight gain or serum levels of estradiol, progesterone, or insulinlike growth
      factor I.

PMID- 9559694
TI  - Effects of rigid plate fixation and subsequent removal on craniofacial growth in
      rabbits.
AB  - OBJECTIVE: To examine the effects of rigid plate fixation (RPF) and subsequent
      removal on craniofacial growth in rabbits. DESIGN: Randomized controlled
      experiment. SUBJECTS: Thirty-two 6-week-old male New Zealand white rabbits.
      INTERVENTIONS: Group 1 underwent exposure of the left nasofrontal suture and
      midzygomatic arch; group 2, RPF of the left nasofrontal suture and midzygomatic
      arch areas; group 3, single osteotomy at left nasofrontal suture and double
      osteotomies at midzygomatic arch with RPF of osteotomies; and group 4, controls.
      At 11 weeks of age, the RPF was removed. Animals were killed at 20 weeks of age.
      Linear and 3-dimensional measurements (euclidean distance matrix analysis) were
      used to evaluate craniofacial regions. RESULTS: In comparison with control
      animals, linear data showed shortening of the left nasal bone in group 3. Groups
      1 through 3 also exhibited shortening of the left zygomatic arch, orbital
      diameter, and anterior midfacial height. Euclidean distance matrix analysis
      showed significant restrictive shape alterations on both the ipsilateral and
      contralateral sides in groups 1 through 3. In comparison with animals in which
      RPF was left in place, linear data showed significant shortening of the orbital
      diameter in groups 1 through 3 and of anterior midface height in groups 2 and 3.
      Euclidean distance matrix analysis showed significant restrictive shape
      alterations on both contralateral and ipsilateral sides. CONCLUSION: Rather than
      preventing restrictive growth disturbances to the growing midface in rabbits, RPF
      with subsequent removal produces a greater amount of restrictive shape alteration
      than RPF that is left in place.

PMID- 9559695
TI  - The tension wire method: a simple, effective means of mandibular fixation.
AB  - OBJECTIVE: To investigate the use of a tension wire band secured to monocortical
      screws for open reduction and internal fixation of simple, displaced, and/or
      unstable mandibular fractures. DESIGN: Retrospective review with follow-up
      duration of at least 6 weeks. SETTING: Level I university trauma center.
      PATIENTS: Twenty-nine patients (27 males and 2 females), aged 7 to 46 years. Ten
      patients had unilateral fractures (1 patient had 3 separate unilateral fractures)
      and 19 had bilateral fractures; 34 of 50 fractures were displaced; 19 were open
      intraorally. The location of fractures and the number (number repaired) were as
      follows: symphysis or parasymphysis, 13 (10); body, 9 (8); angle, 18 (14); ramus,
      6 (4); and subcondylar, 4 (0). Two fractures were each comminuted into 3
      fragments, and 1 patient had unilateral parasymphysial, body, and ramus
      fractures. INTERVENTION: Intermaxillary fixation was done in all patients except
      1 child. Intraoral approaches were used exclusively. A pair of monocortical 2.0
      mm screws were placed perpendicular to fracture lines, with 24-gauge wire loops
      passed around the screws and tightened to bring the fracture into reduction and
      provide stable fixation. A percutaneous trocar system was used to insert screws
      at the body, angle, and ramus sites. RESULTS: There were no instances of
      infection, malunion, or malocclusion in the 33 fractures repaired with this
      technique. A typical intermaxillary fixation with open reduction and internal
      fixation of a posterior fracture was done in less than 2 hours. CONCLUSION: Open
      reduction and internal fixation of simple mandibular fractures with tension wire
      bands around monocortical screws is a simple, quick, and effective technique.

PMID- 9559696
TI  - Gamma probe-directed biopsy of the sentinel node in oral squamous cell carcinoma.
AB  - OBJECTIVE: Management of the N0 neck in head and neck squamous cell carcinoma is
      an important issue for the head and neck surgeon. Experience with radionuclide
      labeled colloid injection to identify a sentinel node in malignant melanoma
      suggests a high level of accuracy for this approach to identify microscopic
      metastasis when present. We set out to explore the feasibility of using the
      handheld gamma probe to identify radiolabeled sentinel nodes in oral squamous
      cell carcinoma. PATIENT POPULATION: Five individuals with N0 necks and accessible
      oral or oropharyngeal primary sites from a major tertiary referral center.
      METHODS: Radiolabel with unfiltered technetium Tc 99m sulfur colloid was injected
      in quadrants around the primary site followed by immediate dynamic
      lymphoscintigraphy. Open biopsy of the sentinel node was accomplished within 2
      hours of injection after extirpation of the primary site. Regional or complete
      neck dissection was performed after sentinel node biopsy. RESULTS: Sentinel node
      biopsy accurately identified one or several nodes in 2 cases, including nodes
      containing metastatic cancer in 1. In the other 3 cases, the radiolabel failed to
      identify the sentinel node despite the presence of metastatic disease in the
      nodes at final pathologic study in 2. CONCLUSIONS: Detection and biopsy of the
      sentinel node are feasible for selected patients with oral head and neck squamous
      cell carcinoma with N0 necks. There is a potential savings of time, cost, and
      morbidity with this approach. However, several substantial problems were
      encountered with the technique in this limited series of patients. Establishing
      the reliability of lymphoscintigraphy in this setting would require testing in a
      much larger patient cohort. Our experience suggests that such an investment may
      not be warranted.

PMID- 9559697
TI  - Pulsatile tinnitus cured by angioplasty and stenting of petrous carotid artery
      stenosis.
AB  - Pulsatile tinnitus may result from turbulent flow within the ipsilateral internal
      carotid artery. Surgical endarterectomy and carotid artery ligation have been
      used to treat atherosclerotic stenosis with or without associated pulsatile
      tinnitus. To our knowledge, this is the first reported case of pulsatile
      tinnitus, attributable to internal carotid artery stenosis, successfully treated
      by angioplasty and stenting.

PMID- 9559699
TI  - Pathologic quiz case 1. Nevus sebaceus.

PMID- 9559698
TI  - Histopathological features of a cochlear implant and otogenic meningitis in
      Mondini dysplasia.
AB  - The temporal bones of a 6-year-old boy with a cochlear implant for profound
      hearing loss associated with Mondini dysplasia were studied histopathologically.
      Despite having severe Mondini dysplasia, he was able to detect sound with the
      implant. On histological examination of the temporal bone, he had more than 10000
      spiral ganglion cells. Histopathological changes in the inner ear associated with
      the cochlear implant were minimal. Patients with severe Mondini dysplasia and
      profound hearing loss may, therefore, benefit from cochlear implantation. In the
      contralateral ear, the patient had suppurative labyrinthitis and meningitis
      associated with chronic otitis media. Histopathological evidence of inflammatory
      necrosis of the round window membrane was consistent with suppurative
      labyrinthitis secondary to otitis media.

PMID- 9559700
TI  - Pathologic quiz case 2. Tracheal tuberculosis (TB).

PMID- 9559701
TI  - Laryngeal electromyography is a cost-effective clinically useful tool in the
      evaluation of vocal fold function.

PMID- 9559702
TI  - Clinical value of laryngeal EMG is dependent on experience of the clinician.

PMID- 9559703
TI  - Laryngeal EMG in clinical neurolaryngology [.

PMID- 9559704
TI  - Methodological difficulties in assessing contributions by community-based
      organizations to improving child health.

PMID- 9559705
TI  - Supporting child psychiatric services using current managed care approaches: you
      can't get there from here.
AB  - For-profit behavioral health care companies have transformed the way mental
      health services are provided for children. Using marketplace approaches,
      companies have "carved out" mental health services for many patients receiving
      care from pediatricians. This report details specific approaches used by these
      firms to maximize profits, minimize the role of child and adolescent
      psychiatrists, and limit clinical services. Understanding for-profit carveouts
      will help primary care pediatricians appreciate the likely consequences of such
      reimbursement incentives for the care of children and their families.

PMID- 9559706
TI  - The impact of interventions by a community-based organization on inner-city
      vaccination coverage: Fulton County, Georgia, 1992-1993.
AB  - OBJECTIVE: To evaluate the impact of interventions by a community-based
      organization on immunization rates. DESIGN: Controlled community intervention
      trial. SETTING AND PARTICIPANTS: Children aged 3 to 59 months in Fulton County,
      Georgia, who were patients of 1 of 4 public clinics (clinic based), or residents
      of 1 of 9 inner-city communities (residence based). INTERVENTIONS: (1) Clinic
      based intervention included monthly review of clinic vaccination records to
      identify undervaccinated children followed by contact with family (reminder
      recall strategy); (2) residence-based intervention included door-to-door
      assessment and education campaigns followed by mobile van vaccinations, temporary
      on-site vaccination stations, free child care and transportation to providers,
      incentives of food and baby products, focus groups, and coalitions with local
      organizations (community saturation with vaccination messages and opportunities).
      OUTCOME MEASURES: Change in vaccination rates after 1 year based on clinic record
      reviews and population surveys. RESULTS: For clinic-based intervention, series
      completion rates improved from 43% (87/204) to 58% (99/170) in intervention
      clinics (P=.003), while rates in control clinics did not change from the baseline
      of 52% (81/157 to 78/150), for a net difference between intervention and control
      arms of +15 percentage points (P=.046). For residence-based intervention, age
      appropriate vaccination rates improved from 44% (154/347) to 61% (260/429) in
      intervention communities (+17 percentage points; P<.001) compared with
      improvement of 44% (78/178) to 58% (129/221) for control communities (+14
      percentage points; P=.004), but the difference between arms was not significant
      (+3 percentage points, P=.78). CONCLUSIONS: Reminder-recall activities by the
      community-based organization improved vaccination rates in intervention clinics
      compared with control clinics. A statistically significant impact on vaccination
      rates could not be detected for residence-based interventions by the community
      based organization.

PMID- 9559707
TI  - Reported difficulties in access to quality care for children with asthma in the
      inner city.
AB  - OBJECTIVE: To characterize perceived access and barriers to quality health care
      for asthma among the caregivers of children in the inner city. DESIGN:
      Multicenter, cross-sectional survey. SETTING: Eight sites in 7 major metropolitan
      US inner cities. PARTICIPANTS: A systematic sample of children with asthma, aged
      4 to 9 years, and their caregivers who resided in census tracts in which at least
      30% of the households were below the 1990 federal poverty guidelines, recruited
      from 25 primary care clinics and 13 emergency departments (EDs) from November 1,
      1992, through October 31, 1993. RESULTS: Of the 1528 children enrolled, 1376 had
      physician-diagnosed asthma and form the basis of this report. This group was
      further divided into 284 children (20.6%) who met all recruitment criteria for
      severe asthma and 207 (15.0%) with mild asthma who met none. Of parents in the
      total sample, 95.6% reported a usual place for short-term asthma care for their
      child; 75.4% used the ED. Children with severe asthma were significantly more
      likely to use the ED than those with mild asthma (84.3% vs 63.0%; P<.01). A usual
      place for follow-up asthma care was reported by 96.7% of subjects. There were no
      differences in access or type of facility used by asthma severity. More than half
      the study group reported difficulty in accessing care for acute asthma attacks
      and for follow-up care with no differences by asthma severity. Among those with
      severe asthma, 47.5% used inhaled steroids or cromolyn, 52.8% used a spacer
      device if they had been prescribed a metered dose inhaler, and 21.2% of children
      older than 6 years were prescribed a peak flowmeter. Patients with mild asthma
      were significantly less likely to report use of all 3 items (steroids or
      cromolyn, 1.4%; spacer device, 15.4%; and peak flowmeter, 3.1%, respectively;
      P<.01). CONCLUSION: Although access to asthma care among children in US inner
      cities appears adequate as determined by the traditional measure of reporting a
      regular source of care, barriers are frequently reported, as are deficiencies in
      the quality of medical care.

PMID- 9559708
TI  - Errors in the use of medication dosage equations.
AB  - BACKGROUND: Calculation errors in prescribing are a well-recognized problem;
      however, no systematic studies of actual errors involving calculation or other
      errors in the use of drug dosage equations are available. OBJECTIVE: To
      characterize the nature and potential adverse consequences of actual prescribing
      errors involving dosage equations. DESIGN: Analysis of the characteristics of 200
      consecutive prescribing errors with potentially adverse outcomes involving dosage
      equations. SETTING: Tertiary care teaching hospital. MEASUREMENTS: Potential
      adverse outcomes, prescribing service, medication class, and the process point at
      which the error was made. RESULTS: Errors most commonly involved children (69.5%)
      and antibiotics (53.5%). Forty-two percent of errors were considered to put the
      patient at risk for a serious or severe preventable adverse outcome. Errors in
      decimal point placement, mathematical calculation, or expression of dosage
      regimen accounted for 59.5% of dosage errors. The dosage equation was wrong in
      29.5% of dosage errors. CONCLUSIONS: The use of equations to determine medication
      dosages presents considerable risk to patients for errant dosing and subsequent
      adverse events or therapeutic failure. Errors may occur in any component of a
      dosage equation. Health care organizations should implement procedures to reduce
      the risk for errors resulting from the use of dosage equations.

PMID- 9559709
TI  - Is bone marrow aspiration needed in acute childhood idiopathic thrombocytopenic
      purpura to rule out leukemia?
AB  - OBJECTIVE: To assess the prevalence of leukemia in a series of bone marrow
      aspiration (BMA) samples collected to confirm provisional diagnoses of acute
      idiopathic thrombocytopenic purpura (ITP) in children. DESIGN: A retrospective
      cohort. SETTING: All BMA reports at The Hospital for Sick Children, Toronto,
      Ontario (a tertiary care pediatric hospital), from January 1, 1984, to May 31,
      1996, were reviewed. PATIENTS: Included were BMAs performed to confirm
      provisional diagnoses of ITP in children (6 months to 18 years of age) with
      "typical" contemporaneous hematologic features of ITP (platelet count, < or =50 x
      10(9)/L; hemoglobin level, > or =100 g/L [6-12 months of age] or > or =110 g/L [>
      1 year of age]; white blood cell count, > or =5 x 10(9)/L [6 months to 6 years of
      age] or > or =4 x 10(9)/L [> 6 years of age]; and neutrophil count, > or =1.5 x
      10(9)/L [6 months to 6 years of age] or > or =2 x 10(9)/L [> 6 years of age]).
      Children with chronic ITP, thrombocytopenia-related chronic conditions, or
      leukemic blasts on peripheral smears were excluded. MAIN OUTCOME MEASURE: The
      finding of leukemia in the BMA report was chosen a priori as the primary outcome
      for the yield of BMA. RESULTS: Four hundred eighty-four BMAs were performed to
      confirm provisional diagnoses of acute childhood ITP. No diagnoses of leukemia
      were revealed in the 332 children with typical hematologic features of ITP. The
      risk of missing the diagnosis of leukemia in this setting is less than 1%.
      CONCLUSIONS: The yield of BMA for leukemia in this setting is low. Routine BMA is
      not necessary for children with typical acute ITP.

PMID- 9559710
TI  - Antibiotics for colds in children: who are the high prescribers?
AB  - OBJECTIVE: To examine physician characteristics associated with being a high
      prescriber of antibiotics for pediatric upper respiratory tract infections
      (URIs). DESIGN AND SETTING: Analysis of 34624 episodes of care for URIs in
      children (younger than 18 years) in the Kentucky Medicaid program from July 1,
      1995, to June 30, 1996. PARTICIPANTS: Primary care physicians with at least 25
      episodes of care (n=205). The proportion of patients with URIs receiving
      antibiotics stratified the sample into low (< or =25th percentile) and high (> or
      =75th percentile) antibiotic prescribers. MAIN OUTCOME MEASURES: Bivariate
      analyses were computed comparing the high and low prescribers. A logistic
      regression model was computed for likelihood of being a high prescriber by number
      of URI episodes, proportion of patients receiving antibiotics that were broad
      spectrum, years since medical school graduation, physician gender, rural/urban
      practice, and specialty. RESULTS: The high prescriber group (n=52) included data
      from 11899 episodes of care, with a mean prescribing rate of 80%. The low
      prescriber group (n=55) included data from 5396 episodes, with a mean prescribing
      rate of 16%. High prescribers were significantly more years away from medical
      school graduation (27 vs 19 years; P<.001) and had managed significantly more URI
      episodes than low prescribers (229 vs 98; P=.001). In the logistic regression,
      compared with pediatricians, the odds ratios of being a high prescriber were 409
      (95% confidence interval [CI], 29-7276) for family practitioners and 318 (95% CI,
      17-6125) for other primary care physicians. CONCLUSION: With the rise of
      antibiotic-resistant bacteria, more focused training regarding treatment of URIs
      is warranted in residency and in continuing medical education forums.

PMID- 9559711
TI  - Contribution of long-bone radiographs to the management of congenital syphilis in
      the newborn infant.
AB  - OBJECTIVE: To determine the contribution of long-bone radiographs to the
      diagnosis and management of newborn infants at risk for congenital syphilis.
      DESIGN: Historical cohort. SETTING: Three large hospitals in Houston, Tex.
      PATIENTS: Eight hundred fifty-three live born infants who were evaluated for the
      presence of congenital syphilis. INTERVENTION: Long-bone radiographs done as part
      of the diagnostic evaluation for the presence of congenital syphilis. MAIN
      OUTCOME MEASURE: Changes in diagnostic classification or management decisions
      that were based on radiographic findings in the long bones. RESULTS: For 450
      infants, radiographic results did not affect management because clinical or
      historical factors were present that dictated treatment: 26 infants had clinical
      symptoms of congenital syphilis (65% [17] had abnormalities on radiographs); and
      424 infants were born to mothers who were untreated or reinfected (5.9% [25] had
      abnormalities on radiographs). All of these infants required a full course of
      therapy regardless of radiologic findings. Born to mothers with possibly
      inadequate therapy (according to 1993 Centers for Disease Control and Prevention
      guidelines), 237 asymptomatic newborn infants were candidates for a single
      injection of penicillin G benzathine if the results of their evaluations were
      normal; of these, 2 (0.8%) had abnormal radiographic findings. Of the 166 infants
      born to adequately treated mothers with appropriately falling serologic titer
      levels, 1 (0.6%) had abnormal radiographic findings (P=.99 between groups). The
      results of the long-bone radiographs did not alter management for any of the 853
      infants who were evaluated for congenital syphilis. CONCLUSIONS: Long-bone
      radiographic findings, often abnormal in symptomatic infants, do not
      differentiate between active infection and past infection. The use of long-bone
      radiographs should be reconsidered in the routine evaluation of infants for
      congenital syphilis.

PMID- 9559712
TI  - A number-needed-to-treat analysis of the use of respiratory syncytial virus
      immune globulin to prevent hospitalization.
AB  - OBJECTIVES: To estimate how many infants in selected high-risk subgroups would
      require treatment with respiratory syncytial virus immune globulin (RSV-IG) to
      avoid 1 hospital admission and to determine whether this is economically
      justified. DESIGN: Cost-benefit analysis. Data from 3 randomized controlled
      trials of RSV-IG are used to estimate the number needed to treat to prevent 1
      hospital admission for respiratory syncytial virus infection. The threshold
      number needed to treat is computed according to a formula incorporating costs and
      benefits of RSV-IG prophylaxis. Estimates of the willingness to pay were obtained
      from a sample of 39 health care providers (35 physicians and 4 nurses). MAIN
      OUTCOME MEASURES: The number needed to treat to prevent 1 hospital admission for
      respiratory syncytial virus infection. The threshold number needed to treat that
      would balance costs with benefits. RESULTS: More than 16 (95% confidence
      interval, 12.5-23.8) infants would need to be treated with RSV-IG to avoid 1
      hospital admission for respiratory syncytial virus infection, ranging from 63 for
      premature infants without chronic lung disease to 12 (confidence interval, 6.3
      100.0) for infants with bronchopulmonary dysplasia. A sensitivity analysis of the
      costs and values of hospital admission for respiratory syncytial virus infection
      and RSV-IG treatment resulted in a weak recommendation against the treatment of
      infants with bronchopulmonary dysplasia and strong recommendations that the costs
      and risks of RSV-IG treatment outweigh the benefits for the combined sample of
      infants and premature infants without lung disease. CONCLUSIONS: The number
      needed-to-treat procedures offer a method to assess evidence of treatment effects
      and decision rules for whether to accept treatment recommendations. Under
      plausible assumptions, treatment with RSV-IG is not recommended for infants
      without lung disease. Institutions can examine cost and benefit assumptions that
      best fit their own practice setting.

PMID- 9559713
TI  - Identification of psychosocial problems in pediatric primary care: do family
      attitudes make a difference?
AB  - OBJECTIVE: To evaluate the affect of families' attitudes about the
      appropriateness of discussing psychosocial concerns on pediatric providers'
      identification of psychosocial problems. DESIGN: These data were collected as
      part of the Greater New Haven Child Health Study, New Haven, Conn. The study
      design was a prospective cohort. SETTING: Families were recruited from a
      stratified random sample of all primary care practices in the greater New Haven
      area. Nineteen of 23 invited practices agreed to participate including 2 prepaid
      practices, 2 neighborhood health centers, and 7 fee-for-service group and 8 fee
      for-service solo practices. PARTICIPANTS: All families of children aged 4 to 8
      years who attended these practices during 2 separate 3-week periods (1 in fall
      1987 and 1 in spring 1988) were invited to participate in the study. Families
      were invited to participate only once, on the first contact with any eligible
      child, using approved procedures. Of 2006 eligible families, 1886 (94%) chose to
      participate. MAIN OUTCOME MEASURE: The outcome variable for these analyses is the
      identification of any behavioral, emotional, or developmental problem by the
      pediatrician on the 13-category checklist. Overall, pediatric clinicians
      identified 27.5% of children with 1 or more psychosocial problems. RESULTS: Our
      data suggest that there is a great deal of discrepancy between what parents
      report is appropriate to do when their children have psychosocial problems and
      what they actually do when they recognize such problems in their children. Most
      (81.1%) believed it was appropriate to discuss 4 or more of the 6 hypothetical
      situations with their children's physician, while only 40.9% actually did discuss
      any of these problems with a physician when a problem occurred. Given the
      correlates of parents who intended to discuss such problems (higher education,
      older age, Euro-American ethnicity, higher income, married, availability of
      medical insurance) the possibility that parents are providing socially acceptable
      responses to such questions seems likely. Further, our data indicate that
      parents' actual reports of discussions of psychosocial problems is unrelated to
      whether physicians identified those problems in children. CONCLUSIONS:
      Pediatricians'judgments about the presence of psychosocial problems in their
      young patients seem to be based on their own observations rather than on what
      parents report. Physician-parent communication about psychosocial problems will
      be increasingly important as primary care physicians assume their role as
      gatekeepers to more expensive services such as mental health interventions.

PMID- 9559714
TI  - Do pediatricians counsel families about sun protection?: a Massachusetts survey.
AB  - BACKGROUND: Pediatric visits during summer months may be especially opportune
      times for sun protection counseling for children and their parents. Few data
      exist on the extent of such counseling. OBJECTIVE: To begin to assess this, we
      surveyed practicing Massachusetts pediatricians to examine current attitudes and
      practices of sun protection counseling. DESIGN AND SETTING: Surveys mailed to
      Massachusetts pediatricians. RESULTS: We received surveys from 756 (60%) of 1263
      eligible Massachusetts pediatricians. Almost 70% indicated that they recommended
      safe sun practices to more than 50% of their patients and their parents during
      the summer months. Counseling regarding seat belt use, bicycle helmet use, and
      smoking prevention were ranked higher in priority than sun protection counseling
      by pediatricians; nutritional guidelines were noted by pediatricians to be a
      parent's most frequent concern. Four variables were independently associated with
      a practitioner's providing safe sun recommendations to more than 50% of parents
      and children: (1) private setting and health maintenance organization
      practitioners as opposed to academic physicians, (2) high ranking of patients'
      safe sun knowledge, (3) high priorities of both parents and physicians for sun
      protection counseling and parental knowledge of safe sun practices relative to
      other recommendations, and (4) pediatrician interest in receiving instructional
      materials. CONCLUSIONS: For the most part, summer sun protection counseling among
      Massachusetts pediatricians seems well integrated into standard practice. Most
      pediatricians rated their confidence level as high for discussing sun protection
      and only a few cited inadequate training or poor reimbursement as barriers toward
      improved counseling. Small steps, such as providing more instructional materials
      to patients and using office-based reminder systems, may improve the quality of
      sun protection counseling practices. Incorporating sunburn prevention into the
      list of routinely recommended injury prevention guidelines for pediatricians
      should be considered.

PMID- 9559716
TI  - Effects of pediatrician characteristics on management decisions in simulated
      cases involving apparent life-threatening events.
AB  - OBJECTIVES: To study variations in the way pediatricians would evaluate and
      manage an infant with an apparent life-threatening event. SUBJECTS AND METHODS: A
      survey was mailed to the chief residents of all pediatric residency training
      programs in the United States in which respondents were presented with a
      simulated case and asked how they would manage an infant who had experienced an
      apparent life-threatening event that did not require resuscitation. The survey
      also explored each physician's tolerance of uncertainty, knowledge of apparent
      life-threatening events, experience, fear of litigation, responsiveness to
      parental demands, and propensity to order tests. MAIN OUTCOME MEASURES: Presumed
      decisions to prescribe antibiotics and/or order home apnea monitoring in a
      simulated case of an infant who had experienced an apparent life-threatening
      event not requiring resuscitation. RESULTS: Logistic regression analysis revealed
      2 characteristics that made significant and independent contributions to
      respondents' presumed decision to prescribe antibiotics: (1) experience with an
      adverse outcome, and (2) propensity to order diagnostic tests. Presumed decisions
      to order a home apnea monitor were notably affected by fear of litigation.
      CONCLUSIONS: These findings suggest that differences in pediatricians'
      characteristics contribute to variations in care. Efforts to make management more
      uniform must consider that decisions are influenced by a host of different
      characteristics and experiences.

PMID- 9559715
TI  - Environmental stressors and emotional status of adolescents who have been in
      special education classes.
AB  - OBJECTIVE: To identify environmental and psychosocial factors associated with
      receiving special education services. DESIGN: The 1992 Minnesota Student Survey,
      an anonymous, self-report survey. SETTING: Minnesota public schools.
      PARTICIPANTS: A total of 121848 adolescents in the 6th, 9th, and 12th grades.
      MAIN OUTCOME MEASURES: Emotional status and potential environmental risk factors
      including family structure, family substance use problems, family violence, and
      sexual abuse were compared between adolescents reporting a history of having been
      in classes for learning problems and a grade- and race-matched comparison group
      of adolescents who had never been in classes for learning problems. Comparisons
      were conducted separately for male and female respondents. RESULTS: Compared with
      adolescents who had never been in classes for learning problems, a significantly
      greater proportion of male and female students who had been in special education
      classes lived in single-parent and nontraditional households, indicated that a
      family member had an alcohol or other drug problem, had witnessed or experienced
      physical abuse, and reported a history of sexual abuse and poor emotional health.
      Most of these associations remained significant when simultaneously controlling
      for the other factors in logistic regression. Significant factors showed modest
      odds ratios in the multivariate analyses (<1.6), except for the emotional status
      variable. Students with a history of receiving special education services had
      from 6 to 14 times the odds of reporting poor emotional health. This association
      was strongest among the youngest adolescents. CONCLUSION: Several environmental
      stressors and psychosocial factors, most notably poor emotional health, are
      associated with a history of special class placement for learning problems.

PMID- 9559718
TI  - Cat-scratch disease in a child with unique magnetic resonance imaging findings.
AB  - OBJECTIVE: To report a patient with cat-scratch disease and the associated
      radiological findings. PATIENT: A previously health 10-year-old boy presenting
      with fever and joint pain. RESULTS: The presence of multiple abnormal foci in the
      bone marrow were noted by magnetic resonance imaging. There was no correlation
      with either radionuclide or conventional radiographic imaging findings. The
      patient's condition was diagnosed as cat-scratch disease by the demonstration of
      elevated antibody titers to the causative organism, Bartonella (formerly
      Rochalimaea) henselae. CONCLUSION: Magnetic resonance imaging may be more
      sensitive to the early bone marrow changes that can occur with cat-scratch
      disease than either radionuclide bone scan or computed tomography.

PMID- 9559717
TI  - Predictors of smoking cessation in adolescents.
AB  - OBJECTIVE: To examine factors associated with cessation of smoking in adolescents
      12 to 18 years of age who smoke cigarettes. DESIGN AND SETTING: Prospective
      school-based cohort study of 1384 New Hampshire high school students surveyed at
      baseline and annually up to 3 subsequent years regarding their substance abuse
      behaviors, including adolescents who smoked 1 or more cigarettes within the past
      30 days at baseline. OUTCOME MEASURES: Cessation behavior was defined by a
      subsequent response indicating nonsmoking status. We examined associations
      between smoking cessation and baseline measurements of the level of addiction
      (cigarette consumption pattern), experience with quitting, intent to quit now and
      in the future, opinion of adults smoking more than 1 pack of cigarettes per day,
      social influences to smoke, sex, and psychological attributes. RESULTS: Of 276
      adolescents who qualified as cigarette smokers at baseline, 123 (44.6%) were
      occasional smokers, 65 (23.6%) were daily smokers of 1 to 9 cigarettes, and 88
      (31.9%) were daily smokers of 10 or more cigarettes. While 39 (14.1%) had smoked
      for 1 year or less, 62 (22.5%) had smoked for 6 or more years. Seventy-five
      (27.2%) reported failed past attempts to quit smoking, 71 (25.7%) reported
      wanting to quit now, and 50 (18.1%) reported definitely intending to be a
      nonsmoker in the future. Seventy-nine smokers (28.6%) described themselves as
      nonsmokers in follow-up surveys. The smoking cessation rate was 46.3% among
      occasional smokers, 12.3% among daily smokers of 1 to 9 cigarettes, and 6.8%
      among daily smokers of 10 or more cigarettes. Smoking cessation was associated
      with occasional smoking status (adjusted odds ratio 6.67 compared with daily
      smokers of 10 or more cigarettes [95% confidence intervals, 2.26-19.69]), and
      definite intentions to quit in the future (2.67 [95% confidence intervals, 1.2
      5.7]). Most of those with definite intentions to quit in the future were
      occasional smokers (92.0%). CONCLUSIONS: This study documents cessation of
      smoking in nearly one third of the adolescent smokers. The cessation rate among
      daily smokers of 10 or more cigarettes per day is comparable with adult cessation
      rates. Adolescents who are less addicted, measured by low frequency of cigarette
      use, are more likely than daily users to quit. In addition, definite intent to
      quit in the future predicts cessation, but only among occasional smokers. In
      contrast with adults, experience with quitting was not associated with a higher
      likelihood of cessation. Pediatricians should focus on keeping occasional smokers
      from moving into daily smoking status, where nicotine addiction begins to play a
      prominent role in maintaining the behavior. Further study is needed to guide
      enhancement of the recruitment of adolescents into cessation, assessment of
      nicotine dependence in daily adolescent smokers, and appropriate use of nicotine
      replacement therapy in this group.

PMID- 9559719
TI  - A comparison of performance between third-year students completing a pediatric
      ambulatory rotation on campus vs in the community.
AB  - OBJECTIVE: To compare the performance of third-year medical students who
      completed the ambulatory component of their pediatric rotation in a community
      setting with the performance of third-year medical students who had their
      ambulatory experience on campus. METHODS: As part of a pilot project to implement
      a third-year Multidisciplinary Ambulatory Clerkship, 61 third-year medical
      students spent 12 weeks rotating through the primary care disciplines of family
      medicine, internal medicine, and pediatric practitioners' offices at sites
      distant from the university campus while 127 students remained on campus for
      their ambulatory experiences in these disciplines. The components of the overall
      pediatric grade consisted of a clinical performance evaluation in the ambulatory
      setting (4 weeks), a clinical performance evaluation on a 4-week inpatient
      rotation, and a grade from a multiple-choice final examination. RESULTS: The
      overall mean+/-SD final pediatric grade of students receiving their ambulatory
      pediatrics experience in the Multidisciplinary Ambulatory Clerkship was 86.5+/
      3.4 compared with 88.0+/-3.4 for students receiving their ambulatory experience
      on campus (P<.007). This difference was accounted for by performance on the
      written final examination. Multidisciplinary Ambulatory Clerkship students had a
      mean+/-SD score of 78.9+/-8.3 and a failure rate of 18% compared with a mean
      score of 83.7+/-8.1 and failure rate of 3.9% for students who remained on campus
      for their ambulatory experience (P<.001 for both comparisons). No differences
      were noted between the 2 groups on their clinical performance evaluations for
      their ambulatory or inpatient experiences. CONCLUSIONS: These data suggest a
      difference in the learning experience between students receiving their pediatric
      ambulatory experience in the community vs on campus. Differences in exposure to
      structured learning experiences that occurred more frequently on campus might
      account for some of the difference in final examination results. Development of a
      standardized, structured learning experience across community sites would seem to
      be an appropriate means of enhancing learning in the community setting.

PMID- 9559720
TI  - Radiological case of the month. Jejunojejunal intussusception caused by a
      trichobezoar with a tail.

PMID- 9559721
TI  - Picture of the month. Generalized lipodystrophy.

PMID- 9559722
TI  - Pathological case of the month. Recurrent respiratory papillomatosis.

PMID- 9559723
TI  - Two unusual pediatric presentations of sarcoidosis.

PMID- 9559724
TI  - Postpartum length of stay.

PMID- 9559725
TI  - The physics of bicycle falls revisited.

PMID- 9559726
TI  - Circumcision and endocarditis prophylaxis.

PMID- 9559727
TI  - Liquefied aftercataract: a complication of continuous curvilinear capsulorhexis
      and intraocular lens implantation in the lens capsule.
AB  - PURPOSE: To describe a new type of aftercataract that contains a liquefied, milky
      white substance between the lens optic and the posterior lens capsule. METHOD: We
      reviewed the medical records of 41 patients identified as having this type of
      aftercataract. RESULTS: All 41 eyes (41 patients) underwent uneventful
      phacoemulsification after continuous curvilinear capsulorhexis and implantation
      of a posterior chamber intraocular lens made from polymethylmethacrylate. Two
      months to 6 years after surgery (average+/-SD, 3.8+/-1.7 years), fibrosis was
      noted evenly along the entire circumference and between the anterior surface of
      the intraocular lens optic and the edge of the capsular opening created by
      continuous curvilinear capsulorhexis. This led to formation of a closed chamber
      between the intraocular lens and the posterior lens capsule, which then
      accumulated a liquefied, milky white substance. Twenty-three of the 41 eyes
      showed liquefied aftercataract in conjunction with other types of aftercataract:
      in 12 eyes with fibrosis, in 11 eyes with Elschnig pearls, and in one eye with a
      Soemmering ring. None of the eyes had any signs of inflammation; six of the 41
      eyes had reduced visual acuity caused exclusively by the liquefied aftercataract.
      Before cataract surgery, 14 eyes were diagnosed with diabetic retinopathy, four
      with glaucoma, and two with uveitis. CONCLUSION: We report a new type of
      aftercataract characterized by a liquefied, milky white substance that
      accumulates between the lens optic and the posterior lens capsule when the
      anterior capsular opening, originally created by continuous curvilinear
      capsulorhexis, becomes occluded with the lens optic.

PMID- 9559728
TI  - Mapping structural to functional damage in glaucoma with standard automated
      perimetry and confocal scanning laser ophthalmoscopy.
AB  - PURPOSE: To develop a quantitative method for analysis of the topographic
      relationship between structural and functional damage in patients with glaucoma.
      METHODS: We studied 26 patients with primary open-angle glaucoma, focal optic
      disk damage, and focal visual field loss. The visual field was evaluated with
      automated perimetry, and the optic disk topography was assessed with a confocal
      scanning laser ophthalmoscope. Topographic measurements were calculated in 10
      degree sectors and compared with a normative database (n=52). The topographic
      relationship of structural damage and functional loss was analyzed. RESULTS: Rim
      area ratio was defined as the ratio of rim area in each 10-degree sector divided
      by the total rim area. This ratio resulted in the identification of one (46%) or
      more (54%) clusters of optic disk sectors as outside normal limits in all 26
      patients (12 and 14 patients, respectively). Twenty-two patients (84%) with
      superior hemifield sensitivity loss tended to have inferior rim defects, and vice
      versa. Nasal visual field defects close to the horizontal midline were matched
      with damaged rim areas close to the vertical midline. CONCLUSIONS: This mapping
      method allows an objective and quantitative evaluation of the optic disk and
      visual field in patients with glaucoma and focal damage. Although the topographic
      relationship between structure and function is characterized by considerable
      interindividual variability, the identification of certain patterns may be useful
      to aid in the evaluation of glaucomatous damage.

PMID- 9559729
TI  - Confocal tomographic angiography of the optic nerve head in patients with
      glaucoma.
AB  - PURPOSE: To demonstrate the superficial and deep blood supply of the optic nerve
      using a new method, confocal tomographic angiography, which combines two new
      techniques, confocal laser scanning ophthalmoscopy and indocyanine green
      angiography, into one system. METHODS: In a prospective study using confocal
      tomographic angiography, we evaluated the correlation between the vascular supply
      of the optic nerve and that of the visual field in 90 eyes of 49 subjects (25
      eyes of 20 subjects with normal visual field and 65 glaucomatous eyes of 39
      subjects with visual field defects; 10 subjects each had one eye with normal
      visual field and one with visual field defects). RESULTS: In 22 of 25 eyes with a
      normal visual field, a diffuse microvascular filling pattern of the optic disk
      area was apparent with no filling defects. The confocal tomographic angiography
      of 49 of 65 glaucomatous eyes had good correlation with their visual field defect
      location. In 20 of 27 eyes with superior visual field loss, an inferior vascular
      filling defect was detected. In 10 of 13 eyes with inferior visual field loss, a
      superior vascular filling defect was detected. In 10 of 15 eyes with superior and
      inferior visual field loss, inferior and superior vascular filling defects were
      detected. Finally, in nine of 10 eyes with total visual field loss, no
      vascularity of the optic disk could be detected. CONCLUSION: Confocal tomographic
      angiography is a new imaging technology that may be applied for the evaluation of
      the vascular supply of the optic nerve head.

PMID- 9559730
TI  - Acquired pit of the optic nerve: a risk factor for progression of glaucoma.
AB  - PURPOSE: To examine acquired pit of the optic nerve as a risk factor for
      progression of glaucoma. METHODS: In a retrospective longitudinal study, 25 open
      angle glaucoma patients with acquired pit of the optic nerve were compared with a
      group of 24 open-angle glaucoma patients without acquired pit of the optic nerve.
      The patients were matched for age, mean intraocular pressure, baseline ratio of
      neuroretinal rim area to disk area, visual field damage, and duration of follow
      up. Serial optic disk photographs and visual fields of both groups were evaluated
      by three independent observers for glaucomatous progression. RESULTS: Of 46
      acquired pits of the optic nerve in 37 eyes of 25 patients, 36 pits were located
      inferiorly (76%) and 11 superiorly (24%; P < .001). Progression of optic disk
      damage occurred in 16 patients (64%) in the group with acquired pit and in three
      patients (12.5%) in the group without acquired pit (P < .001). Progression of
      visual field loss occurred in 14 patients (56%) in the group with acquired pit
      and in six (25%) in the group without pit (P=.04). Bilateral acquired pit of the
      optic nerve was present in 12 patients (48%). Disk hemorrhages were observed more
      frequently in the group with acquired pit (10 eyes, 40%) compared with the group
      without pit (two eyes, 8%; P=.02). CONCLUSION: Among patients with glaucoma,
      patients with acquired pit of the optic nerve represent a subgroup who are at
      increased risk for progressive optic disk damage and visual field loss.

PMID- 9559731
TI  - Effects of laser in situ keratomileusis (LASIK) on the corneal endothelium.
AB  - PURPOSE: To assess the effects of laser in situ keratomileusis (LASIK) on the
      corneal endothelium. METHODS: In a prospective study, the corneal endothelium of
      98 eyes of 65 consecutive patients (mean age, 41 years; range, 22 to 66 years)
      was photographed before, 2 weeks after, and 12 weeks after LASIK for the
      correction of 2.75 to 14.5 diopters of myopia. Theoretical ablation depths were
      200 to 330 microm below the corneal surface. Cell density, coefficient of
      variation, and percent of hexagonal cells were determined using 150 to 200 cells
      from each image. Eighty-eight eyes (91%) of 59 patients had a history of contact
      lens wear. RESULTS: The mean+/-SD preoperative endothelial cell density was
      2,549+/-365 cells per mm2, and the mean coefficient of variation was 0.35+/-0.06.
      There was no statistically significant change in the mean endothelial cell
      density or mean coefficient of variation of cell size at the 2-week (2,561+/-360
      cells per mm2 and 0.35+/-0.06) or 12-week (2,541+/-364 cells per mm2 and 0.35+/
      0.05) postoperative examinations. The percent of hexagonal cells was not
      significantly changed 2 weeks postoperatively; however, 12 weeks postoperatively
      (P=.0413, two-tailed t test), the percent of hexagonal cells was decreased by 1%.
      CONCLUSIONS: Corneal endothelial cell density and morphology were unchanged 2 and
      12 weeks after LASIK for the correction of up to 14.5 diopters of myopia. In this
      LASIK study, the correction of up to 14.5 diopters of myopia appears to cause no
      clinically significant effect on corneal endothelial cell density or morphology.

PMID- 9559732
TI  - Analgesic efficacy and safety of nonpreserved ketorolac tromethamine ophthalmic
      solution following radial keratotomy. Ketorolac Radial Keratotomy Study Group.
AB  - PURPOSE: To compare the analgesic efficacy and safety of nonpreserved ketorolac
      tromethamine 0.5% with those of its vehicle in the treatment of postsurgical
      ocular pain following radial keratotomy. METHODS: This study employed a
      multicenter, double-masked, randomized, parallel-group design. Radial keratotomy
      patients were treated with either nonpreserved ketorolac tromethamine 0.5% or its
      vehicle four times daily for up to 3 days following surgery. Patients were
      provided with an escape medication (acetaminophen) for use only as needed for
      intolerable pain. RESULTS: Patients treated with ketorolac reported significantly
      greater pain relief (P < or =.023), less pain intensity (P < or =.047), less use
      of escape medication (P < or =.001), fewer symptoms of ocular discomfort
      (P=.024), and fewer sleep disturbances (P < or =.013) than did patients treated
      with vehicle. No treatment-related adverse events were reported in the ketorolac
      group, and only one treatment-related adverse event was reported in the vehicle
      group. Most other safety findings were equivalent in the two treatment groups
      except that there were significantly less eyelid erythema (P=.026) and eyelid
      edema (P < or =.001) in the ketorolac group. CONCLUSIONS: Nonpreserved ketorolac
      tromethamine 0.5% ophthalmic solution was significantly more effective than, and
      as safe as, vehicle in the treatment of postoperative pain associated with radial
      keratotomy. Therefore, topical ketorolac may be a valuable treatment option for
      the maintenance of patient comfort following refractive surgery.

PMID- 9559733
TI  - Experimental study of tetrodotoxin, a long-acting topical anesthetic.
AB  - PURPOSE: To determine the effectiveness and toxicity of tetrodotoxin for use as a
      long-acting topical anesthetic. METHODS: Four groups of six rabbits each received
      a 40-microl aliquot of either tetrodotoxin in one of three concentrations (10 mM,
      1 mM, or 0.1 mM) or proparacaine 0.5% into the inferior conjunctival cul-de-sac
      of one eye, with the fellow eye of each rabbit receiving 40 microl of a 60-mM, pH
      4.3 sodium citrate vehicle as a control. Corneal sensation was tested for up to 8
      hours after administration of drugs, and response was noted by no blink, partial
      blink without full eyelid closure, and full blink. Slit-lamp examination at 12
      and 24 hours after administration and pachymetry before and 24 hours after
      administration were performed to detect corneal toxicity. RESULTS: Rabbits
      receiving all three concentrations of tetrodotoxin did not demonstrate any ocular
      irritation, corneal thickening, or signs of systemic toxicity. At a dose of 10
      mM, tetrodotoxin produced an anesthetic effect lasting up to 8 hours. At 1 mM,
      tetrodotoxin was an effective but shorter-acting anesthetic. At 0.1 mM,
      tetrodotoxin had no significant anesthetic effect. Proparacaine-treated rabbits
      initially were anesthetic, but this effect was largely gone by 1 hour and
      completely gone by 3 hours. CONCLUSIONS: Tetrodotoxin is a long-acting topical
      anesthetic in the rabbit cornea. Although additional toxicity studies are
      required, tetrodotoxin may provide an effective, long-lasting topical anesthetic
      for use in pain control after corneal procedures such as photorefractive
      keratectomy.

PMID- 9559734
TI  - Efficient reactivation of latent herpes simplex virus type 1 infection by excimer
      laser keratectomy in the experimental rabbit ocular model.
AB  - PURPOSE: To investigate the role of excimer laser keratectomy as a trigger for
      the reactivation of latent HSV type 1 (HSV-1) in the New Zealand rabbit ocular
      model. There are conflicting reports in the current literature about reactivation
      of HSV-1 after excimer laser photoablation. METHODS: New Zealand rabbits were
      inoculated topically with HSV-1 McKrae or W strain in each eye, and culture
      positive dendritic keratitis was documented on day 7. After the establishment of
      latency (21+ days), animals were divided into three groups: group I animals
      underwent excimer laser photoablation in each eye; group II animals received
      intrastromal injections of sterile water to act as positive controls (a standard
      method); and group III animals received no treatment and represented spontaneous
      shedders. All eyes were swabbed daily from days 1 through 10 and plated on A549
      cells. Recovery of HSV-1 on days 1 through 10 postinduction was analyzed to
      compare the efficiency of the different methods of viral reactivation. RESULTS:
      Reactivation of latent HSV-1 after excimer treatment was observed in nine (45%)
      of 20 eyes and was equivalent to the rate of reactivation seen in the positive
      control animals (eight [44.4%] of 18 eyes) (P=.99). Both of these rates were
      significantly greater than those of the untreated animals (one [5.6%] of 18 eyes)
      (P=.018). CONCLUSION: Excimer laser keratectomy appears to be an efficient
      trigger for the reactivation of latent HSV-1 in the New Zealand rabbit ocular
      model.

PMID- 9559735
TI  - Long-term tamoxifen citrate use and potential ocular toxicity.
AB  - PURPOSE: To estimate the prevalence of abnormalities in visual function and
      ocular structures associated with the long-term use of tamoxifen citrate.
      METHODS: A single-masked, cross-sectional study involving multiple community and
      institutional ophthalmologic departments was conducted with a volunteer sample of
      303 women with breast cancer currently taking part in a randomized clinical trial
      to determine the efficacy of tamoxifen (20 mg/day) in preventing recurrences.
      Participants included women who had never been on drug (n=85); women who had
      taken tamoxifen for an average of 4.8 years, then been off the drug for an
      average of 2.7 years (n=140); and women who had been on tamoxifen continuously
      for an average of 7.8 years (n=78). Women were evaluated by questionnaire,
      psychophysical testing, and clinical examination to determine any abnormalities
      in visual function and the comparative prevalences of corneal, lens, retinal, and
      optic nerve pathology. RESULTS: There were no cases of vision-threatening ocular
      toxicity among the tamoxifen-treated participants. Compared with nontreated
      participants, the tamoxifen-treated women had no differences in the activities of
      daily vision, visual acuity measurements, or other tests of visual function
      except for color screening. Intraretinal crystals (odds ratio [OR]=3.58, P=.178)
      and posterior subcapsular opacities (OR=4.03, P=.034) were more frequent in the
      tamoxifen-treated group. CONCLUSIONS: Women should have a thorough baseline
      ophthalmic evaluation within the first year of initiating tamoxifen therapy and
      receive appropriate follow-up evaluations.

PMID- 9559736
TI  - A North Carolina macular dystrophy phenotype in a Belizean family maps to the
      MCDR1 locus.
AB  - PURPOSE: To describe the clinical findings of an autosomal dominant macular
      dystrophy in a family of Mayan Indian ancestry in Belize, Central America, and to
      determine its molecular genetic relationship with the original North Carolinian
      family. METHODS: We performed comprehensive ophthalmic examinations on 56 members
      of a single family living in Chicago, Illinois, and Belize, Central America.
      Fundus photography and fluorescein angiography were performed on 17 affected
      subjects and six affected family members were serially examined over a 12-year
      period. Blood was collected from 26 individuals, and DNA was extracted for
      genotyping. Two-point linkage, multipoint linkage, and haplotype analysis was
      performed. RESULTS: In 17 affected individuals, the clinical features were
      consistent with the diagnosis of North Carolina macular dystrophy. Multipoint
      linkage analysis generated a peak lod score of 5.6 in the MCDR1 region. The
      haplotype associated with the disease was, however, different from that of the
      original North Carolinian family. CONCLUSIONS: This family has an autosomal
      dominant macular dystrophy that is clinically indistinguishable from North
      Carolina macular dystrophy (MCDR1). Our findings indicate that the mutated gene
      in this Belizean family maps precisely to the same region as that of the North
      Carolina macular dystrophy (MCDR1) locus. This study provides evidence that MCDR1
      occurs in various ethnic groups and that there is no evidence of genetic
      heterogeneity.

PMID- 9559737
TI  - Ocular manifestations of giant cell arteritis.
AB  - PURPOSE: To report the ocular manifestations of giant cell arteritis using the
      strict criterion of a positive temporal artery biopsy for diagnosis of giant cell
      arteritis. METHODS: In a prospective study from 1973 to 1995, we investigated 170
      patients whose diagnosis of giant cell arteritis was confirmed on temporal artery
      biopsy. At the initial visit, all patients were questioned regarding systemic and
      ocular signs and symptoms of giant cell arteritis and underwent ophthalmic,
      erythrocyte sedimentation rate (Westergren), and C-reactive protein evaluations.
      Any patient with a high index of suspicion of giant cell arteritis was
      immediately started on systemic corticosteroid therapy and had temporal artery
      biopsy performed as soon as possible. RESULTS: Eighty-five (50.0%) of the 170
      patients with giant cell arteritis proven by temporal artery biopsy presented
      with ocular involvement. Ocular symptoms in patients with ocular involvement were
      visual loss of varying severity in 83 (97.7%), amaurosis fugax in 26 (30.6%),
      diplopia in five (5.9%), and eye pain in seven (8.2%); ocular ischemic lesions
      consisted of arteritic anterior ischemic optic neuropathy in 69 (81.2%), central
      retinal artery occlusion in 12 (14.1%), cilioretinal artery occlusion in 12 (of
      55 patients with satisfactory fluorescein angiography [21.8%]), posterior
      ischemic optic neuropathy in six (7.1%), and ocular ischemia in one (1.2%). In
      almost every patient with giant cell arteritis, fluorescein fundus angiography
      disclosed occlusive disease of the posterior ciliary arteries. CONCLUSION:
      Because giant cell arteritis is a potentially blinding disease and its early
      diagnosis is the key to preventing blindness, it is important to recognize its
      various ocular manifestations.

PMID- 9559738
TI  - Occult giant cell arteritis: ocular manifestations.
AB  - PURPOSE: To report the incidence, visual symptoms, and ocular signs of occult
      giant cell arteritis in patients who initially presented with visual symptoms and
      ocular signs of giant cell arteritis. Occult giant cell arteritis was defined as
      ocular involvement by giant cell arteritis without any systemic symptoms and
      signs of giant cell arteritis. METHODS: In a prospective study from 1973 to 1995,
      we investigated 85 patients who had ocular involvement caused by giant cell
      arteritis and whose diagnosis of giant cell arteritis was confirmed on temporal
      artery biopsy. At the initial visit, patients were questioned specifically on
      systemic and ocular symptoms and signs of giant cell arteritis at or before the
      onset of visual disturbance. Erythrocyte sedimentation rate (Westergren) and C
      reactive protein level were evaluated before the start of systemic corticosteroid
      therapy. RESULTS: Eighteen (21.2%) of 85 patients had occult giant cell
      arteritis. There was no significant difference in age and sex distribution
      between patients with and without systemic symptoms of giant cell arteritis.
      Although both groups of patients had abnormal erythrocyte sedimentation rate and
      C-reactive protein level, there was a significant difference in erythrocyte
      sedimentation rate (P < .0001) and C-reactive protein level (P=.0133), these
      being relatively lower in patients with occult giant cell arteritis. The ocular
      symptoms in the 18 patients with occult giant cell arteritis were visual loss of
      varying severity in 18 (100%), amaurosis fugax in six (33.3%), diplopia in two
      (11.1%), and eye pain in one (5.6%). Ocular ischemic lesions consisted of
      anterior ischemic optic neuropathy in 17 (94.4%), central retinal artery
      occlusion in two (11.1%), and cilioretinal artery occlusion in two (of 11
      patients with satisfactory fluorescein angiography [18.2%]). The ocular symptoms
      and ischemic lesions were seen in a variety of combinations. CONCLUSIONS: Because
      occult giant cell arteritis is a potential cause of blindness, its early
      diagnosis is the key to preventing blindness; it is important to recognize that
      21.2% of patients with giant cell arteritis and visual loss do not have any
      systemic symptoms of giant cell arteritis. Thus, in persons older than 55 years,
      amaurosis fugax or visual loss, development of an acute ocular ischemic lesion
      (particularly arteritic anterior ischemic optic neuropathy), and abnormal C
      reactive protein level, with or without elevated erythrocyte sedimentation rate
      and systemic symptoms, should raise a high index of suspicion for giant cell
      arteritis.

PMID- 9559739
TI  - The ophthalmology of intracranial vascular abnormalities.
AB  - PURPOSE: To provide a practical review of the ophthalmologic manifestations of
      intracranial vascular abnormalities. METHODS: We reviewed ocular manifestations
      of the most common intracranial vascular abnormalities: intracranial aneurysms,
      carotid-cavernous fistulas, arteriovenous malformations, and cavernous
      malformations. RESULTS: Unruptured aneurysms can compress the third cranial nerve
      and the anterior visual pathways. Ruptured aneurysms and subarachnoid hemorrhage
      can result in Terson syndrome and papilledema. Direct and indirect carotid
      cavernous fistulas most commonly cause the classic triad of proptosis,
      conjunctival chemosis, and cranial bruit but can masquerade as chronic
      conjunctivitis. Arteriovenous malformations, with or without hemorrhage, may
      compress portions of the retrochiasmal pathways, causing visual field loss.
      Cavernous malformations, when in the brainstem, commonly cause abnormalities of
      supranuclear, nuclear, and fascicular ocular motility. CONCLUSIONS: The
      ophthalmologist may be the first physician to encounter clinical manifestations
      of intracranial vascular abnormalities that may herald devastating neurologic
      complications. Prompt diagnosis facilitates appropriate management and therapy.

PMID- 9559740
TI  - Capsular bag distention syndrome noted 5 years after intraocular lens
      implantation.
AB  - PURPOSE: To describe a case of capsular bag distention syndrome with opaque
      contents noted 5 years after intraocular lens implantation. METHODS: A 66-year
      old man underwent phacoemulsification after circular capsulorhexis and
      intraocular lens implantation in the left eye. Five years later, the posterior
      capsule was vaulted far posteriorly, the capsular opening was apparently sealed
      by the lens optic, and the bag contents were slightly opacified. Two years later,
      the contents of the hyperdistended capsular bag showed intensified opacity,
      causing definite blurred vision. RESULTS: The opacified medium was emptied from
      the capsular bag posteriorly into the vitreous after Nd:YAG laser capsulotomy,
      and the distended capsule was restored. CONCLUSIONS: Our findings suggest that
      the contents were collagens produced by residual lens epithelial cells or
      necrotic and/or apoptotic autolyzed lens epithelial cells.

PMID- 9559741
TI  - Lattice corneal dystrophy type 1 in a Canadian kindred is associated with the
      Arg124 --> Cys mutation in the kerato-epithelin gene. sgupta@ogh.on.ca.
AB  - PURPOSE: To identify the mutation responsible for lattice corneal dystrophy type
      1 in an extended Canadian kindred. METHODS: A search for a mutation in the
      candidate gene, kerato-epithelin, was carried out by single-strand conformation
      polymorphism and sequencing analyses. RESULTS: AC --> T mutation at position 417
      was detected in exon 4 of the kerato-epithelin gene, which is expected to cause
      an Arg124 --> Cys change. This is the same nucleotide change described previously
      in two Swiss families with lattice corneal dystrophy type 1. CONCLUSION: Although
      the possibility that the three families (two previously described Swiss families
      and this Canadian kindred) are related has not been excluded, it appears that the
      unique phenotype of lattice corneal dystrophy type 1 is caused by this particular
      amino acid change.

PMID- 9559742
TI  - The use of processed pericardial tissue in anterior ocular segment
      reconstruction.
AB  - PURPOSE: To report the use of processed pericardial tissue in reconstructing the
      anterior ocular segment. METHOD: Three case reports. RESULT: Processed
      pericardial tissue was found to be a helpful adjunct in providing tectonic
      support and promoting epithelialization in the cases described. CONCLUSION:
      Processed pericardial tissue has potential application to a variety of anterior
      ocular segment conditions.

PMID- 9559743
TI  - Aerobic and anaerobic microbiology of dacryocystitis.
AB  - PURPOSE: To investigate the aerobic and anaerobic microbiology of dacryocystitis.
      METHOD: Retrospective review of the 62 clinical and microbiologic records
      collected between 1980 and 1990. RESULTS: Aerobic or facultative bacteria were
      recovered in 32 cases (52%), anaerobic bacteria only in 20 cases (32%), mixed
      aerobic and anaerobic bacteria in seven cases (11%), and fungi in three cases
      (5%). A total of 94 organisms (1.5 per specimen), which included 56 aerobic or
      facultative anaerobic organisms, 35 anaerobic organisms, and three fungi, were
      recovered. The predominant aerobic and facultative bacteria were Staphylococcus
      aureus (15 isolates), Staphylococcus epidermidis (13 isolates), and Pseudomonas
      species (seven isolates). The most frequently recovered anaerobes were
      Peptostreptococcus species (13 isolates), Propionibacterium species (12
      isolates), Prevotella species (four isolates), and Fusobacterium species (three
      isolates). The predominant fungus was Candida albicans (two isolates).
      Polymicrobial infection was present in 28 cases (45%). CONCLUSION: These data
      highlight the potential importance of anaerobic bacteria in dacryocystitis.

PMID- 9559744
TI  - Unilateral peripapillary myelinated retinal nerve fibers associated with
      strabismus, amblyopia, and myopia.
AB  - PURPOSE: To describe the association of unilateral peripapillary myelinated
      retinal nerve fibers with myopia, strabismus, and amblyopia and to propose a
      possible pathologic mechanism. METHODS: Four patients who have the findings
      associated with unilateral peripapillary myelinated nerve fibers are described
      and reviewed. RESULT: All patients had poor visual outcomes despite treatment
      with full cycloplegic refraction and appropriate patching. CONCLUSIONS: Although
      the origin of this association is unknown, we believe that peripapillary
      myelinated nerve fibers in a unilateral myopic eye may be secondary to an
      imbalance between the process of myelination and the formation of the lamina
      cribrosa. Good results have been reported with amblyopic therapy; however, it is
      our experience that these patients are somewhat refractory to amblyopia therapy.

PMID- 9559745
TI  - Acute posterior multifocal placoid pigment epitheliopathy with corneal stromal
      infiltrates.
AB  - PURPOSE: To report the association of perilimbal corneal stromal infiltrates with
      acute posterior multifocal placoid pigment epitheliopathy. METHOD: Case report.
      RESULTS: A 29-year-old woman with bilateral fundus lesions typical of acute
      posterior multifocal placoid pigment epitheliopathy presented with peripheral
      corneal stromal infiltrates that resolved with fundus lesions. CONCLUSION:
      Corneal stromal infiltrates may be associated with characteristic fundus lesions
      of acute posterior multifocal placoid pigment epitheliopathy.

PMID- 9559746
TI  - Osseous metaplasia in proliferative vitreoretinopathy.
AB  - PURPOSE: To report the clinicopathologic features of intraocular osseous
      production in association with proliferative vitreoretinopathy. METHOD: The
      clinical and histopathologic features of two patients with proliferative
      vitreoretinopathy and intraocular bone formation are reviewed. RESULTS:
      Preretinal osseous tissue incorporated in the proliferative vitreoretinopathy was
      surgically removed in one patient, and osseous tissue was present in the
      proliferative vitreoretinopathy in the enucleated eye of the other patient.
      CONCLUSIONS: Bone formation, presumably from metaplastic retinal pigment
      epithelium, may be present in proliferative vitreoretinopathy tissue. The
      intraocular bone is present internal rather than external to the neurosensory
      retina.

PMID- 9559747
TI  - Systemic small noncleaved cell lymphoma presenting as a posterior choroidal mass.
AB  - PURPOSE: To describe a patient with intraocular involvement by systemic, small
      noncleaved cell lymphoma. METHODS: Case report and review of the literature.
      RESULTS: A patient presented with a diffusely elevated choroidal mass. Systemic
      evaluation led to the diagnosis of unsuspected disseminated lymphoma. CONCLUSION:
      Small noncleaved cell lymphoma should be included in the differential diagnosis
      of a choroidal mass.

PMID- 9559748
TI  - Recognizing structural damage to the optic nerve head and nerve fiber layer in
      glaucoma.

PMID- 9559749
TI  - Recognizing structural damage to the optic nerve head and nerve fiber layer in
      glaucoma.

PMID- 9559750
TI  - A system for classifying mechanical injuries of the eye (globe)

PMID- 9559751
TI  - The relationship between progression of visual field defects and retrobulbar
      circulation in patients with glaucoma.

PMID- 9559752
TI  - Regression of cytomegalovirus retinitis associated with protease-inhibitor
      treatment in patients with AIDS.

PMID- 9559753
TI  - Can depression be managed appropriately in primary care?
AB  - This review considers the necessary conditions for appropriate management of
      depression in primary care. While discussion of primary care management has often
      focused on the recognition of depression, recognition alone is not sufficient.
      Recent research demonstrates that primary care management of depression
      frequently fails to meet recommended standards for intensity of treatment and
      follow-up. Several recent randomized trials show that effective treatment of
      depression in primary care is possible but will require significant changes in
      current practice. Prerequisites for more effective management of depression in
      primary care include appropriate patient education, systematic monitoring of care
      processes and outcomes, and easy access to the full range of psychiatric
      consultation services.

PMID- 9559754
TI  - Managing behavioral health care: an employer's perspective.
AB  - Employee life cycle events and behavioral health disorders impact productivity
      and well-being. Employers use wellness initiatives and employee assistance or
      work-family programs to help manage those factors that can distract employees
      from performing optimally. Employer-sponsored health benefits are designed to
      protect employees from the catastrophic costs of illness. However, today's plan
      designers struggle with employee and employer affordability that does not
      compromise quality or effectiveness. In 1990, Digital Equipment Corporation,
      Maynard, Mass., shifted its strategy from an indemnity model to a managed care
      model that uses health maintenance organizations. Comprehensive standards are
      used to ensure the delivery of quality behavioral health care that is cost
      effective, is delivered at the clinically appropriate levels, and uses a broad
      continuum of treatment approaches with measurable outcomes.

PMID- 9559755
TI  - Economic outcomes with antidepressant pharmacotherapy: a retrospective intent-to
      treat analysis.
AB  - Herein we describe a retrospective intent-to-treat evaluation designed to compare
      the natural course of antidepressant utilization and direct health service
      expenditures for the treatment of a single episode of major depression among
      patients enrolled in a multistate network-model health maintenance organization
      and initially prescribed either a tricyclic antidepressant (amitriptyline or
      nortriptyline) or the serotonin selective reuptake inhibitor (SSRI) fluoxetine.
      Patient-level paid-claims data for the period July 1, 1988, through December 31,
      1991, were abstracted. During the above time frame, fluoxetine was the only SSRI
      available in the United States. Patients prescribed amitriptyline were more than
      three times as likely to require a change in antidepressant pharmacotherapy (OR =
      3.27, 95% CI = 2.31 to 5.49), while patients prescribed nortriptyline were nearly
      four times more likely to change medication (OR = 3.82, 95% CI = 2.74 to 6.83)
      relative to patients initially prescribed fluoxetine. Consistent with our intent
      to-treat design, all accrued health service expenditures were assigned to the
      pharmacotherapeutic option initially prescribed. Multivariate analyses revealed
      that initiation of antidepressant pharmacotherapy with amitriptyline resulted in
      a 25.7% increase in per capita depression-related health service expenditures per
      year, while initiation of antidepressant pharmacotherapy with nortriptyline
      resulted in a 28.1% increase in per capita depression-related health service
      expenditures per year relative to patients initially prescribed fluoxetine. A
      financial break-even point was achieved at the conclusion of Month 5, at which
      time all three intent-to-treat cohorts had comparable health service expenditures
      in total. From a financial perspective, results stemming from this inquiry
      suggest that the initiation of antidepressant pharmacotherapy with an SSRI is
      warranted.

PMID- 9559756
TI  - Psychotropic drug use during pregnancy: weighing the risks.
AB  - Although psychotropic drugs have not been tested or approved by the Food and Drug
      Administration for use during pregnancy, some women continue to take these
      medications while they are pregnant, particularly since mood and anxiety
      disorders cluster in women during childbearing years. The relative risks and
      benefits of drug therapy for these women must be weighed with each patient and
      treatment limited to those situations in which risks to mother and fetus from the
      disorder are presumed to exceed the risk of drug treatment. Risks of psychotropic
      drug use during pregnancy include teratogenic effects, direct neonatal toxicity,
      and the potential for longer term neurobehavioral sequelae. Of growing concern is
      the risk of untreated psychiatric disorder as it may potentially affect
      fetoplacental integrity and fetal central nervous system development.
      Coordination of care with the patient, her husband or partner, and the
      obstetrician is essential, as is careful medical record documentation when
      treating pregnant patients with psychiatric disorders.

PMID- 9559757
TI  - Course of mood and anxiety disorders during pregnancy and the postpartum period.
AB  - Because the onset of mood and anxiety disorders often occurs during the
      childbearing years, many women may be taking psychotropic medications for these
      disorders when they conceive. These medications easily diffuse across the
      placenta, and their impact on the fetus is of concern. But discontinuation may
      lead to relapse, in which case psychiatric symptoms may affect the fetus.
      Thoughtful treatment planning presents a dilemma to the clinician. Limited data
      suggest heightened vulnerability to relapse of mood and anxiety disorders in
      women during the postpartum period. Pregnancy appears to exacerbate symptoms of
      obsessive-compulsive disorder, while panic disorder patients may remain well
      after discontinuing medication. Future studies should address the prevalence and
      relapse rates of mood and anxiety disorders, particularly after medication
      discontinuation, among pregnant women.

PMID- 9559758
TI  - Postpartum mood disorders: diagnosis and treatment guidelines.
AB  - Mood disturbance occurs commonly during the postpartum period. The symptoms may
      be transient and relatively mild (as in postpartum blues) or may be associated
      with significant impairment of functioning (as in postpartum depression and
      puerperal psychosis). Despite the prevalence of postpartum mood disorders,
      depressive symptoms that emerge during the puerperium are often overlooked.
      Puerperal affective illness places the mother at risk for the development of
      recurrent depression and has also been associated with significant long-term
      effects on child development and behavior. Therefore, the prompt recognition and
      efficacious treatment of puerperal mood disorders are essential in order to avoid
      adverse outcomes for both mother and infant. This article discusses the
      evaluation of postpartum mood disturbance and offers guidelines for the treatment
      of affective illness during the puerperium.

PMID- 9559759
TI  - Psychotropic medications in lactation.
AB  - The use of psychotropic medications during lactation has not been investigated in
      a controlled and systematic fashion. The literature is laden with case reports
      and small case series containing numerous confounds that render the establishment
      of definitive treatment guidelines tenuous. The increasing number of women who
      plan to breast-feed and the high rate of psychiatric illness during the
      postpartum period underscore the need to develop such guidelines. A MEDLINE
      search was conducted for key words either in the titles or abstracts of
      publications citing the use of psychotropic medications in lactating women and
      describing the pharmacokinetics of medication excretion into breast milk. The
      publications identified span over three decades. The largest single study by one
      group of investigators examined 12 mother-infant pairs. The majority of studies
      report their results as a ratio of the breast milk concentration to the maternal
      serum concentration (milk/plasma [M/P]) ratio. Estimations that use the M/P ratio
      of the infant daily dose range from 0.1% to 6.2% of the maternal dose. Few
      studies attempt to account for the complex variations in the maternal, breast
      milk, and infant physiologic environments. The major confounds of the studies
      reviewed include (1) failure to document portion of breast milk assayed (foremilk
      versus hindmilk), (2) limited metabolite assay, (3) limited assay sensitivity (1
      25 ng/mL), not of research quality, (4) concomitant maternal and/or infant
      medications, and (5) medication exposure during pregnancy. Despite these
      confounds, there are remarkably few reports of adverse effects on nursing infants
      exposed to psychotropic medications in breast milk. The limited data confirm that
      psychotropic medications are excreted into breast milk and that the infant is
      exposed to these medications. The ideal breast milk study that accounts for the
      confounds identified has not been completed. The complex matrix of breast milk
      and the changing infant metabolic capacity will require a more detailed analysis
      with assays of improved sensitivity. Despite the limited reports of adverse
      effects on nursing infants, the limitations of the available literature and
      minimal sample sizes make it premature to recommend specific medications from a
      given class. There is inadequate data on nursing infant exposure to multiple
      medications to support changing medication to a different agent in an otherwise
      stable patient. An individualized risk/benefit assessment with the empirical goal
      of minimizing infant exposure while maintaining maternal emotional health is the
      ideal approach.

PMID- 9559760
TI  - The impact of maternal psychiatric illness on infant development.
AB  - Maternal depression and anxiety are associated with compromises in infant and
      maternal social and emotional functioning. In this paper, we briefly review the
      literature on this topic and present some preliminary findings on a group of
      mothers in treatment for major depressive disorder, panic disorder, or obsessive
      compulsive disorder. The findings suggest that the symptom reports of treated
      mothers with established DSM diagnoses were similar overall to those of control
      mothers. However, the mothers' psychiatric illness had a compromising effect on
      their interactions with their infants and on their infants' social and emotional
      functioning. The implications of these results are discussed.

PMID- 9559761
TI  - Managed care versus managed money.

PMID- 9559762
TI  - Role of medication in managed care for depression.

PMID- 9559763
TI  - Role of psychiatrists in managed care systems.

PMID- 9559764
TI  - Cerebral CO2 vasoreactivity evaluation with and without changes in intrathoracic
      pressure in comatose patients.
AB  - It is well established that cerebral blood flow (CBF) is sensitive to variations
      in arterial PCO2 (PaCO2) and can be influenced by changes in jugular venous
      return due to elevated intrathoracic pressure. Therefore, we compared cerebral
      CO2 vasoreactivity when PaCO2 was altered either by changing inspired PCO2 or
      tidal volume. In addition, we sought to determine if noninvasive transcranial
      Doppler ultrasonography can be used instead of invasive CBF measurement to
      determine cerebral CO2 vasoreactivity. In 36 mechanically ventilated patients in
      coma due to acute brain lesion, we evaluated CBF by continuous jugular
      thermodilution, middle cerebral artery flow velocity (Vm) by transcranial Doppler
      ultrasonography, intracranial pressure (ICP; in only 23 of them) by
      intraventricular catheter, systemic and pulmonary hemodynamic variables, and
      arterial and jugular bulb blood gases. Measurements were taken at four levels of
      PaCO2 (25, 30, 35, and 40 mmHg) by modifying in a random order either tidal
      volume or inspired PCO2. Cerebral, pulmonary, and systemic hemodynamic changes
      were similar in magnitude during both methods of altering PaCO2. From the highest
      to the lowest PaCO2, CBF decreased from 61+/-7 to 36+/-4 ml/min/100 g (p < 0.001,
      mean +/- SE), Vm from 89+/-7 to 65+/-5 cm/s (p < 0.001), and ICP from 29+/-2 to
      12+/-2 mmHg (p < 0.001), but cerebral perfusion pressure remained constant,
      ranging from 65+/-3 to 67+/-4 mmHg (p = NS). Arteriojugular oxygen content
      difference increased from 3.2+/-0.2 to 5.7+/-0.4 ml/dl (p < 0.001). Eleven of the
      20 patients with a preserved CBF response to CO2 survived to 6 months, whereas
      only two of the 16 patients with an altered response were alive at 6 months (p <
      0.05). When compared with CBF by jugular thermodilution, the rates of sensitivity
      and specificity of transcranial Doppler ultrasonography to detect impaired
      cerebral CO2 vasoreactivity were 69% and 65%, respectively. In conclusion, the
      reduction of PaCO2 from 40 to 25 mmHg by modifying either tidal volume or
      inspired PCO2 resulted in similar effects on cerebral, pulmonary, and systemic
      circulations. Cerebral CO2 vasoreactivity is of prognostic value in brain-injured
      patients when determined using CBF but may be misleading when evaluated using
      velocities measured by transcranial Doppler ultrasonography.

PMID- 9559765
TI  - Correlation of transcranial Doppler sonography mean flow velocity with cerebral
      blood flow in patients with intracranial pathology.
AB  - Several studies suggest that relative changes in cerebral blood flow (CBF) may be
      assessed via transcranial Doppler sonography (TCD). The present study
      investigates the correlation between changes in TCD-mean flow velocity (Vm) and
      changes in CBF in patients with a variety of types of intracranial pathology
      undergoing cerebrovascular reactivity tests. After informed consent was obtained,
      32 patients presenting with stenoses of brain-supplying arteries (n = 13),
      cerebral vascular malformations (n = 6), surgical decompression for subarachnoid
      hemorrhage (n = 2), brain edema after closed head injury (n = 8), or hepatic
      encephalopathy (n = 3) were studied. The patients were divided into two groups
      for different reactivity tests. Patients in group 1 (awake or sedated, n = 18)
      received a 1-g dose of acetazolamide intravenously. In group 2 (n = 14),
      mechanical ventilation was adjusted to produce a 20% decrease in arterial CO2
      tension compared with baseline. Regional CBF was measured using xenon-enhanced
      computed tomography (Xe-CT). Xe-CT scans at the levels of the basal ganglia and
      the lateral ventricles were performed during a 4.5-min xenon wash-in period.
      Bilateral flow velocity was measured in the middle cerebral artery using a 2-MHz
      pulsed TCD system. Mean arterial blood pressure, heart rate, and end-tidal CO2
      were continuously recorded during the procedure. After baseline measurements and
      either alteration of CO2 or application of acetazolamide, the cerebrovascular
      reactivity was assessed at 20 min by a second measurement of CBF, TCD, and all
      other physiologic variables. The correlation coefficient for relative changes of
      MCA territory CBF versus Vm and for the overall population was r = 0.82. In
      groups 1 and 2, the r values were 0.39 and 0.5, respectively. Correlation
      coefficients did not exceed r = 0.4 in any subgroup-classification based on
      diagnosis. The close correlation between changes in CBF and Vm (r = 0.82) in
      patients with heterogeneous intracranial pathology seems to show that TCD is a
      measure of CBF. However, in groups 1 and 2 and in subgroups formed of patients
      classified according to diagnoses, data dispersion suggests that the actual
      correlation is weaker. Relation of changes in Vm to those in CBF may depend on
      the underlying diagnosis. These data indicate that the correlation between Vm and
      CBF may vary with intracranial pathology.

PMID- 9559766
TI  - Effect of mild hypothermia and the 21-aminosteroid U-74389G on neurologic and
      histopathologic outcome after transient spinal cord ischemia in the rabbit.
AB  - Mild hypothermia and the 21-aminosteroids have both been neuroprotective in
      several models of cerebral ischemia. In this study we compared the effects of
      mild hypothermia and the 21-aminosteroid U-74389G, alone and in combination on
      neurologic and histopathologic outcome after temporary spinal cord ischemia.
      Forty male anesthetized New Zealand white rabbits were randomized to four groups
      (n = 10): (a) normothermia (control); (b) U-74389G (3 mg/kg intravenously [i.v.]
      before aortic occlusion, 1.5 mg/kg i.v. and 10 mg/kg intraperitoneally after
      occlusion); (c) mild hypothermia (4 degrees C epidural temperature decrease); and
      (d) mild hypothermia combined with U-74389G. Spinal cord ischemia was produced by
      40 min of infrarenal aortic balloon occlusion. Forty-eight hours after the
      procedure, the neurologic status of the animals was assessed (Tarlov score) and
      the animals were killed for histologic evaluation. In the normothermic control
      group, eight of 10 animals became paraplegic. There was a significant reduction
      of the incidence of paraplegia and overall neurologic deficits and a significant
      improved Tarlov score in the mild hypothermic group (one animal paraplegic) and
      in the group with both mild hypothermia and U-74389G (two animals with a mild
      paraparesis). The histopathologic scores showed significantly less damage in both
      hypothermic groups. In group 2, U-74389G administration did not improve
      neurologic or histopathologic outcomes. The results of the current study
      demonstrate that a slight decrease of intraischemic spinal cord temperature
      significantly improved neurologic and histopathologic outcomes after experimental
      spinal cord ischemia. Protection by the 21-aminosteroid at normothermic
      conditions, or additional protection when U-74389G was added to mild hypothermia,
      could not be demonstrated.

PMID- 9559767
TI  - Effects of closed head trauma and lipopolysaccharide on body temperature, brain
      tissue water content, and PGE2 production in rats.
AB  - Closed head trauma (CHT) increases brain tissue prostaglandin E2 (PGE2)
      concentration, and that increase is associated with cerebral edema formation and
      worsening of the neurologic severity score (NSS). Injection of the bacterial
      endotoxin lipopolysacharride (LPS) increases cerebral and hypothalamic PGE2, and
      the hypothalamic increase is associated with increased body temperature. The
      present study determined (a) whether LPS-induced increase of PGE2 causes brain
      edema or worsens NSS and (b) whether CHT increases hypothalamic PGE2 and thereby
      increases body temperature. Halothane-anesthetized rats were divided into four
      groups: group 1 = surgery with no CHT and no LPS (n = 8); group 2 = surgery with
      LPS and no CHT (n = 8); group 3 = surgery with CHT and no LPS (n = 8); and group
      4 = surgery with CHT plus LPS (n = 8). NSS was determined at 1 and 24 h after
      injury, and brain tissue PGE2 and edema were determined when animals were killed
      24 h after injury. As compared with group 1, LPS alone, but not CHT or CHT plus
      LPS, increased rectal temperature. CHT and CHT plus LPS, but not LPS alone
      increased brain water content and worsened NSS. LPS, CHT, and CHT plus LPS all
      increased hypothalamic and cerebral PGE2 production. We conclude that although
      LPS and CHT increased PGE2 levels, LPS alone did not affect neurologic status or
      brain edema, CHT did not increase rectal temperature, and addition of LPS to CHT
      did not aggravate the sequelae of CHT.

PMID- 9559768
TI  - A case of severe cerebral trauma in a patient under chronic treatment with
      cyclosporine A.
AB  - A case of severe cerebral head injury in a child, chronically treated with
      cyclosporine A after orthotopic liver transplantation, is presented. The initial
      Glasgow Coma Scale score after the motor vehicle accident was 3, and computed
      tomography showed multiple sites of intracerebral bleeding, an epidural hematoma,
      and signs of perifocal edema. Although these lesions are normally associated with
      a poor outcome, the child recovered unexpectedly well. In brain injury, a lucid
      interval can be followed by secondary neurologic deterioration due to a loss of
      high-energy metabolites, a release of neurotransmitters, and an increase in
      intracellular Ca2+. These events finally led to cell damage in the penumbra of an
      ischemic infarction. Among other drugs, immunosuppressants such as cyclosporine A
      have been shown to exhibit neuroprotective properties in experimental models if
      given during this time interval of secondary neurologic deterioration. Although
      human data on these effects are still lacking, we conclude that neuroprotective
      actions of cyclosporine A may have been involved in the favorable outcome in this
      14-year-old boy.

PMID- 9559769
TI  - The upper limit of cerebral blood flow autoregulation in acute intracranial
      hypertension.
AB  - The present series of experiments was performed to investigate the influence of
      acute intracranial hypertension on the upper limit (UL) of cerebral blood flow
      (CBF) autoregulation. Three groups of eight rats each--one with normal
      intracranial pressure (ICP) (2 mmHg), one with ICP = 30 mmHg, and one with ICP =
      50 mmHg--were investigated. Intracranial hypertension was maintained by
      continuous infusion of lactated Ringer's solution into the cisterna magna, where
      the pressure was used as ICP. Cerebral perfusion pressure (CPP), calculated as
      mean arterial blood pressure (MABP)-ICP, was increased stepwise by continuous
      intravenous infusion of norepinephrine. CBF was calculated by the intracarotid
      133Xe method. In all three groups the corresponding CBF/CPP curve included a
      plateau where CBF was independent of changes in CPP, showing intact
      autoregulation. At normal ICP the UL was found at a CPP of 141 +/-2 mmHg, at ICP
      = 30 mmHg the UL was 103+/-5 mmHg, and at ICP = 50 mmHg the UL was found at 88+/
      7 mmHg. This shift of the UL was more pronounced than the shift of the lower
      limit (LL) of the CBF autoregulation found previously. We conclude that
      intracranial hypertension is followed by both a shift toward lower CPP values and
      a narrowing of the autoregulated interval between the LL and the UL.

PMID- 9559770
TI  - A case of shock subsequent to treatment of intracranial hypertension by mannitol
      injection combined with hyperventilation.
AB  - This report describes a sudden decrease in blood pressure after conservative
      treatment of acute intracranial hypertension. A 63-year-old woman with acute
      hydrocephalus after undergoing clipping of an aneurysm of the right
      supracerebellar artery developed increased intracranial pressure, necessitating
      surgical management. On the operating table, the patient developed Cushing's
      reflex. Mannitol injection combined with hyperventilation was begun immediately
      to reduce her intracranial pressure. Fifteen minutes later, a sudden and
      prolonged suppression of circulation was observed (blood pressure 65/35-85/40
      mmHg, heart rate 90-100 beats/min). Postoperatively, computed tomography of the
      head showed compression of the brain stem. We believe that this patient's blood
      pressure decrease was related to a sudden reduction of intracranial pressure and
      that mannitol injection was principally responsible for this occurrence.

PMID- 9559771
TI  - A multifunctional helmet for noninvasive neuromonitoring.
AB  - Simultaneous and continuous recording and processing of different noninvasive
      neuromonitoring parameters were carried out, including spontaneous and evoked
      bioelectrical brain activities obtained by new "active electrodes," transcranial
      Doppler sonographic measurements using robotic probes, a multiscan principle for
      three-dimensional transcranial Doppler imaging, and recording of near-infrared
      spectroscopic data. The recording and processing were carried out over periods of
      some hours with a new recording technique integrated in a helmet construction.

PMID- 9559772
TI  - Response to "Statistics and hypothermia".

PMID- 9559773
TI  - Cefepime versus ceftriaxone for empiric treatment of hospitalized patients with
      community-acquired pneumonia. The Cefepime Study Group.
AB  - Effective empiric treatment of pneumonia requires antibiotic coverage against
      gram-negative and gram-positive pathogens, including drug-resistant isolates. We
      compared the safety and efficacy of intravenous (i.v.) cefepime (2 g administered
      every 12 h) to those of i.v. ceftriaxone (1 g administered every 12 h) for the
      empiric treatment of hospitalized patients with community-acquired pneumonia. Of
      the 115 patients randomized to the study, 86 (cefepime recipients, n = 40;
      ceftriaxone recipients, n = 46) were evaluated for clinical efficacy (clinically
      evaluated patients). Favorable clinical outcomes (cure or improvement) were
      comparable among clinically evaluated patients in the cefepime and ceftriaxone
      treatment arms (95.0 versus 97.8%, respectively; 95% confidence interval for
      treatment difference [data for ceftriaxone group minus data for cefepime group], 
      5.1 to +10.8%). The most common bacteria isolated from patients in both treatment
      groups were Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus
      aureus. In clinically evaluated patients with a microbiologic response, all
      (100%) of the 32 pathogens from cefepime-treated patients and 97.4% (38 of 39) of
      the pathogens from ceftriaxone-treated patients were eradicated (documented or
      presumed eradication). The one persistent infection in the ceftriaxone group was
      caused by Pseudomonas fluorescens. Both treatments were well tolerated. Our data
      thus suggest that cefepime and ceftriaxone have comparable safety and efficacy
      for the treatment of pneumonia in hospitalized patients.

PMID- 9559774
TI  - Thirteen-year evolution of azole resistance in yeast isolates and prevalence of
      resistant strains carried by cancer patients at a large medical center.
AB  - Drug resistance is emerging in many important microbial pathogens, including
      Candida albicans. We performed fungal susceptibility tests with archived isolates
      obtained from 1984 through 1993 and fresh clinical isolates obtained from 1994
      through 1997 by testing their susceptibilities to fluconazole, ketoconazole, and
      miconazole and compared the results to the rate of fluconazole use. All isolates
      recovered prior to 1993 were susceptible to fluconazole. Within 3 years of
      widespread azole use, we detected resistance to all agents in this class. In
      order to assess the current prevalence of resistant isolates in our hematologic
      malignancy and transplant patients, we obtained rectal swabs from hospitalized,
      non-AIDS, immunocompromised patients between June 1995 and January 1996. The
      swabs were inoculated onto sheep's blood agar plates containing 10 microg of
      vancomycin and 20 microg of gentamicin/ml of agar. One hundred one yeasts were
      recovered from 97 patients and were tested for their susceptibilities to
      amphotericin B, fluconazole, flucytosine, ketoconazole, and miconazole. The
      susceptibility pattern was then compared to those for all clinical isolates
      obtained throughout the medical center. The antifungal drug histories for each
      patient were also assessed. The yeasts from this surveillance study were at least
      as susceptible as the overall hospital strains. There did not appear to be a
      direct linkage between prior receipt of antifungal agent therapy and carriage of
      a new, drug-resistant isolate. Increased resistance to newer antifungal agents
      has occurred at our medical center, but it is not focal to any high-risk patient
      population that we studied. Monitoring of susceptibility to antifungal agents
      appears to be necessary for optimizing clinical therapeutic decision making.

PMID- 9559775
TI  - Antibiotic-induced lipopolysaccharide (LPS) release from Salmonella typhi: delay
      between killing by ceftazidime and imipenem and release of LPS.
AB  - It has been suggested that the antibiotic-induced release of lipopolysaccharide
      (LPS) is an important cause of the development of septic shock in patients
      treated for severe infections caused by gram-negative bacteria. Beta-lactam
      antibiotics change the integrity of the bacterial cell envelope by binding to
      penicillin-binding proteins (PBP) in the membrane and thus may affect the amount
      of LPS that is released and the kinetics of that release. In this respect,
      ceftazidime at intermediate concentrations binds with a high affinity to PBP 3
      and PBP 1a and thus can induce filament formation in addition to killing, whereas
      imipenem preferentially binds to PBP 2 and PBP 1b, leading to spheroplast
      formation and rapid cell lysis. We investigated the effects of these antibiotics
      on the killing and the release of the radioactively labelled LPS of Salmonella
      typhi Ty 21A. A mathematical model was developed to calculate the delay between
      bacterial killing and LPS release, designated the lag time. At antibiotic
      concentrations inducing equal killing, the amount of LPS released was the same
      for both antibiotics. Only after 6 h of incubation at antibiotic concentrations
      above 0.5 microg/ml, the amount of 3H-LPS released was slightly higher
      (approximately 1.2-fold) in incubations with ceftazidime than in those with
      imipenem, and the maximum releases of the total label were 33.2% +/- 0.89% and
      27.1% +/- 0.45%, respectively. Despite the clear concentration-dependent effect
      on the bacterial killing and subsequent LPS release, the lag time was independent
      of the antibiotic concentration. For ceftazidime as well as imipenem the lag time
      amounted to approximately 60 min. In conclusion, our findings imply that the
      mechanism of antibiotic-induced LPS release is independent of the PBP affinities
      for these beta-lactam antibiotics. Furthermore, once the organism is killed by
      either imipenem or ceftazidime, the rate of LPS release from S. typhi does not
      differ according to the antibiotic with which the organism is killed, and there
      is little difference in the relative amount of LPS released.

PMID- 9559776
TI  - Use of pharmacodynamic parameters to predict efficacy of combination therapy by
      using fractional inhibitory concentration kinetics.
AB  - Combination therapy with antimicrobial agents can be used against bacteria that
      have reduced susceptibilities to single agents. We studied various tobramycin and
      ceftazidime dosing regimens against four resistant Pseudomonas aeruginosa strains
      in an in vitro pharmacokinetic model to determine the usability of combination
      therapy for the treatment of infections due to resistant bacterial strains. For
      the selection of an optimal dosing regimen it is necessary to determine which
      pharmacodynamic parameter best predicts efficacy during combination therapy and
      to find a simple method for susceptibility testing. An easy-to-use, previously
      described E-test method was evaluated as a test for susceptibility to combination
      therapy. That test resulted in a MICcombi, which is the MIC of, for example,
      tobramycin in the presence of ceftazidime. By dividing the tobramycin and
      ceftazidime concentration by the MICcombi at each time point during the dosing
      interval, fractional inhibitory concentration (FIC) curves were constructed, and
      from these curves new pharmacodynamic parameters for combination therapy were
      calculated (i.e., AUCcombi, Cmax-combi, T>MIC-combi, and T>FICi, where AUCcombi,
      Cmax-combi, T>MIC-combi, and T>FICi are the area under the FICcombi curve, the
      peak concentration of FICcombi, the time that the concentration of the
      combination is above the MICcombi, and the time above the FIC index,
      respectively). By stepwise multilinear regression analysis, the pharmacodynamic
      parameter T>FICi proved to be the best predictor of therapeutic efficacy during
      combination therapy with tobramycin and ceftazidime (R2 = 0.6821; P < 0.01). We
      conclude that for combination therapy with tobramycin and ceftazidime the T>FICi
      is the parameter best predictive of efficacy and that the E-test for
      susceptibility testing of combination therapy gives promising results. These new
      pharmacodynamic parameters for combination therapy promise to provide better
      insight into the rationale behind combination therapy.

PMID- 9559777
TI  - Duration and clinical relevance of postantibiotic effect in relation to the
      dosing interval.
AB  - The influence of half-life on the postantibiotic effect (PAE) of tobramycin
      against Pseudomonas aeruginosa and Staphylococcus aureus was investigated during
      one dosing interval. Tobramycin half-lives of 0.5 to 2.5 h were simulated in an
      in vitro model, and the PAE was determined by an enzymatic inactivation method at
      different time points, i.e., when the tobramycin concentrations were 20x, 5x, and
      1x the MIC. At the time point during therapy when the tobramycin concentrations
      had declined to 1x the MIC, at a tobramycin half-life of 0.5 h, the times of the
      PAEs were approximately 0.7 and 1.7 h for P. aeruginosa and S. aureus,
      respectively, and the PAE disappeared completely at half-lives corresponding to
      those found in humans (i.e., 2 to 2.5 h). The PAE itself cannot be fully
      explained by the presence of free intrabacterial tobramycin or the emergence of
      resistant subpopulations. The explanation for the disappearance of the PAE during
      the dosing interval may therefore be explained by the repair of sublethal damage.
      Since the standard method of determining the PAE in animal models is somewhat
      different from the method used for measurement of the PAE in vitro, the
      conditions under which the PAE is measured in vivo were also simulated in the in
      vitro model. This resulted in PAEs longer than those found by the standard method
      of obtaining in vitro PAE measurements. We conclude that the PAE of tobramycin,
      as determined by conventional in vitro methods, has virtually no clinical
      importance. PAEs determined in vivo may have some clinical relevance, but they
      are probably primarily caused by sub-MIC effects.

PMID- 9559778
TI  - Role of ABC transporters in aureobasidin A resistance.
AB  - Aureobasidin A (AbA) has strong antifungal effects arising from an unusual
      mechanism. We show that AbA interacts with ATP-binding cassette (ABC)
      transporters in yeast and mammalian cells. We isolated a gene of Saccharomyces
      cerevisiae that conferred resistance to AbA when the gene was present in multiple
      copies. The gene was identical to YOR1/YRS1, which confers resistance to
      oligomycin, reveromycin, and organic anions, none of which have structures
      similar to that of AbA. We also isolated an aur3R recessive mutant of S.
      cerevisiae with increased resistance to AbA. Northern hybridization showed that
      the aur3R mutant expressed not only YOR1 but also the ABC transporter-encoding
      gene PDR5 at high levels. Genetic studies showed that the aur3R mutant had a
      mutation in the PDR1 gene, which encodes a transcriptional regulator of PDR5 and
      YOR1. Analysis of a yor1 disruptant of the aur3/pdr1 mutant showed that both the
      functional YOR1 gene and the mutation in PDR1 were necessary for AbA resistance.
      These results suggest that YOR1 is more important than PDR5 for AbA resistance.
      We found in Candida albicans a novel gene whose sequence was similar to the
      sequence of YOR1 in S. cerevisiae. The amino acid sequence of the C. albicans
      YOR1 homolog showed no significant similarity to the sequences of CDR1 and CDR2,
      which are ABC transporters of C. albicans. Furthermore, AbA inhibited the efflux
      of the anticancer agent vincristine through P glycoproteins in cancer cells with
      multidrug resistance.

PMID- 9559779
TI  - Amphotericin B in lipid emulsion: stability, compatibility, and in vitro
      antifungal activity.
AB  - Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid
      suspensions have been developed. Preliminary studies have suggested that AmB in
      Intralipid (IL) may be as effective as, but less toxic than, conventional
      formulations of AmB, but few data are available regarding its stability,
      compatibility, or in vitro antifungal activity. A compatibility study was done to
      evaluate the effects of AmB concentrations in IL containing either 10 or 20%
      soybean oil. The effects of temperature, shaking, and AmB and IL concentrations
      on the stability of AmB-IL suspensions were analyzed by visual inspection and
      liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to
      that of AmB alone against reference strains of Candida species was determined by
      using a broth macrodilution method in accordance with National Committee for
      Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were
      lightly shaken retained more than 90% of the AmB concentration over 21 days when
      stored at either 4 or 23 degrees C. Varying the AmB concentration did not appear
      to affect the stability of AmB-IL. However, a precipitate was formed when
      mixtures with more than 30% lipid as a proportion of the total volume were
      centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities
      against reference strains of yeasts. Further pharmacologic and clinical studies
      with AmB-IL are warranted, although AmB should not be combined with IL in
      concentrations capable of producing a precipitate.

PMID- 9559780
TI  - In vitro and in vivo antifungal activity of amphotericin B lipid complex: are
      phospholipases important?
AB  - Amphotericin B lipid complex for injection (ABLC) is a suspension of amphotericin
      B complexed with the lipids L-alpha-dimyristoylphosphatidylcholine (DMPC) and L
      alpha-dimyristoylphosphatidylglycerol. ABLC is less toxic than amphotericin B
      deoxycholate (AmB-d), while it maintains the antifungal activity of AmB-d. Active
      amphotericin B can be released from ABLC by exogenously added (snake venom,
      bacteria, or Candida-derived) phospholipases or by phospholipases derived from
      activated mammalian vascular tissue (rat arteries). Such extracellular
      phospholipases are capable of hydrolyzing the major lipid in ABLC. Mutants of C.
      albicans that were resistant to ABLC but not AmB-d in vitro were deficient in
      extracellular phospholipase activity, as measured on egg yolk agar or as measured
      by their ability to hydrolyze DMPC in ABLC. ABLC was nevertheless effective in
      the treatment of experimental murine infections produced by these mutants.
      Isolates of Aspergillus species, apparently resistant to ABLC in vitro (but
      susceptible to AmB-d), were also susceptible to ABLC in vivo. We suggest that
      routine in vitro susceptibility tests with ABLC itself as the test material may
      not accurately predict the in vivo activity of ABLC and that the enhanced
      therapeutic index of ABLC relative to that of AmB-d in vivo may be due, in part,
      to the selective release of active amphotericin B from the complex at sites of
      fungal infection through the action of fungal or host cell-derived
      phospholipases.

PMID- 9559782
TI  - Antiproliferative and apoptotic activities of ketonucleosides and keto-C
      glycosides against non-small-cell lung cancer cells with intrinsic drug
      resistance.
AB  - We compared the biological activity of a new group of keto-C-glycosides to that
      of a narrow spectrum of unsaturated ketonucleosides in a panel of non-small-cell
      lung cancer (NSCLC) cells with various levels of intrinsic resistance to standard
      chemotherapy drugs. Unlike cisplatin, etoposide, adriamycin, or taxol, for which
      a significant difference in the cytotoxic effect was observed between sensitive
      cell lines (H460, H125, and MGH4) and drug-resistant cell lines (H661, MGH7, and
      FADU), nucleoside analogs were equally cytotoxic in NSCLC cell lines, with
      compound 92 being 10-fold more active than compound 43, 44, 81, or 161, while
      compound 3 was the least active. Apoptotic measurements with flow cytometric
      analysis of terminal uridine deoxynucleotide nick end-labeled cells revealed that
      the cytotoxic activity of these nucleosides correlated with their potency to
      induce apoptosis. Compound 92 triggered death in cells with wild-type p53,
      mutated p53, or p53 gene deletion. Our findings suggest that keto-C-glycosides
      may be promising alternative anticancer agents which merit further studies in in
      vivo cancer models refractory to standard chemotherapy drugs.

PMID- 9559781
TI  - Effect of dirithromycin on Haemophilus influenzae infection of the respiratory
      mucosa.
AB  - Macrolides have properties other than their antibiotic action which may benefit
      patients with airway infections. We have investigated the effect of dirithromycin
      (0.125 to 8.0 microg/ml) on the interaction of Haemophilus influenzae with
      respiratory mucosa in vitro using human nasal epithelium, adenoid tissue, and
      bovine trachea. Dirithromycin did not affect the ciliary beat frequency of the
      nasal epithelium or the transport of mucus on bovine trachea, but dirithromycin
      (1 microg/ml) did reduce the slowing of the ciliary beat frequency and the damage
      to the nasal epithelium caused by H. influenzae broth culture filtrate.
      Amoxicillin (2 microg/ml) did not reduce the effects of the H. influenzae broth
      culture filtrate. H. influenzae infection of the organ cultures for 24 h caused
      mucosal damage and the loss of ciliated cells. Bacteria adhered to damaged
      epithelium and to a lesser extent to mucus and unciliated cells. Incubation of H.
      influenzae with dirithromycin at sub-MICs (0.125 and 0.5 microg/ml) prior to
      infection of the organ cultures did not reduce the mucosal damage caused by
      bacterial infection. By contrast, incubation of adenoid tissue with dirithromycin
      (0.125 to 1.0 microg/ml) for 4 h prior to assembling the organ culture reduced
      the mucosal damage caused by subsequent H. influenzae infection by as much as
      50%. The number of bacteria adherent to the mucosa was reduced, although the
      tissue that had been incubated with dirithromycin (0.125 and 0.5 microg/ml) did
      not inhibit bacterial growth. This was achieved by a reduction in the amount of
      damaged epithelium to which H. influenzae adhered and a reduction in the density
      of bacteria adhering to mucus. We conclude that dirithromycin at concentrations
      achievable in vivo markedly reduces the mucosal damage caused by H. influenzae
      infection due to a cytoprotective effect.

PMID- 9559783
TI  - In vivo activity of HSR-903, a new fluoroquinolone, against respiratory
      pathogens.
AB  - The in vivo activity of HSR-903, a new fluoroquinolone, against major bacteria
      which cause respiratory tract infections was evaluated. HSR-903 was active
      against experimental respiratory tract infections in mice challenged with
      penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae and
      Haemophilus influenzae strains. Treatment with HSR-903 reduced the bacterial
      numbers in infected murine lungs. In accord with the pulmonary clearance results,
      the rates of survival for mice treated with HSR-903, sparfloxacin, levofloxacin,
      ciprofloxacin, and benzylpenicillin were 50, 30, 10, 0, and 0%, respectively, 14
      days after being infected with penicillin-resistant S. pneumoniae. A
      pharmacokinetic study with pneumonic mice showed that the levels of HSR-903 in
      the lungs were seven to eight times higher than those in the plasma. These
      results indicate that clinical studies of HSR-903 against respiratory tract
      infections may be warranted.

PMID- 9559784
TI  - Imiquimod, a patient-applied immune-response modifier for treatment of external
      genital warts.
AB  - Genital human papillomavirus infection is one of the most common sexually
      transmitted diseases. Imiquimod is a new agent, an immune-response modifier, that
      has been demonstrated to have potent in vivo antiviral and antitumor effects in
      animal models. The present prospective, multicenter, double-blind, randomized,
      vehicle-controlled trial evaluated the efficacy and safety of daily patient
      applied imiquimod for up to 16 weeks for the treatment of external genital warts.
      Wart recurrence was investigated during a 12-week treatment-free follow-up
      period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94
      (52%) patients treated with 5% imiquimod cream, 13 of 90 (14%) patients treated
      with 1% imiquimod cream, and 3 of 95 (4%) vehicle-treated patients; the
      differences between the groups treated with vehicle and imiquimod were
      significant (P < 0.0001). For subjects who completed the follow-up period,
      recurrence rates after a complete response were 19% (9 of 48 patients) in the 5%
      imiquimod cream group, 17% (2 of 12) in the 1% imiquimod cream group, and 0% (0
      of 3) in the vehicle-treated group. There were no systemic reactions, although
      local skin reactions (generally of mild or moderate severity) were common,
      particularly in the 5% imiquimod cream group. Local reactions caused two patients
      to discontinue treatment. The most frequently reported local skin reactions were
      erythema, excoriation or flaking, and erosion. Patient-applied 5% imiquimod cream
      is effective for the treatment of external genital warts and has a favorable
      safety profile.

PMID- 9559786
TI  - Generation and characterization of a mutant of influenza A virus selected with
      the neuraminidase inhibitor BCX-140.
AB  - Influenza neuraminidase (NA) plays an important role in viral replication, and
      characterization of viruses resistant to NA inhibitors will help elucidate the
      role of active-site residues. This information will assist in designing better
      inhibitors targeted to essential active-site residues that cannot generate drug
      resistant mutations. In the present study we used the benzoic acid-based
      inhibitor BCX-140 to select and characterize resistant viruses. BCX-140 binds to
      the NA active site in an orientation that is opposite that of a sialic acid-based
      compound, 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid (GANA).
      Thus, the guanidino group of BCX-140 binds to Glu-276, whereas in GANA the
      guanidino group binds to Glu-119. We passaged influenza A/Singapore/1/57 (H2N2)
      in Madin-Darby canine kidney cells in the presence of BCX-140, and virus
      resistant to this inhibitor was selected after six passages. The NA of this
      mutant was still sensitive to inhibition by BCX-140. However, the mutant virus
      was resistant to BCX-140 in plaque and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays. Sequence analysis of hemagglutinin (HA)
      and NA genes revealed changes in both, although none were in the active site of
      the NA. Depending on the method of selection of the resistant virus, two types of
      changes associated with the sialic acid binding site were seen in the HA. One is
      a change in HA1 of Ala-133 to Thr, a residue close to the binding site, while the
      other change was Arg-132 of HA1 to Gln, which in HA1 of serotype H3 is a sialic
      acid contact (Asn-137). Binding studies revealed that both types of resistant
      viruses had reduced receptor binding affinity compared to that of the wild type.
      Thus, resistance to BCX-140 was generated by modifying the HA. NA active-site
      residue 276 may be essential for activity, and thus, it cannot be changed to
      generate resistance. However, drug-induced changes in the HA can result in a
      virus that is less dependent on NA activity for growth in cells and, hence,
      resistant to NA inhibitors.

PMID- 9559785
TI  - Accumulation of norfloxacin by Mycobacterium aurum and Mycobacterium smegmatis.
AB  - The modified fluorescence method was used to determine the accumulation of
      norfloxacin by Mycobacterium aurum A+ and Mycobacterium smegmatis mc(2)155. By
      using an exogenous norfloxacin concentration of 10 microg/ml, a steady-state
      concentration (SSC) of 160 to 180 ng of norfloxacin/mg of cells was obtained for
      M. aurum, and an SSC of 120 to 140 ng of norfloxacin/mg of cells obtained for M.
      smegmatis. For both species of mycobacteria, the SSC was achieved within 5 min.
      The silicon oil method was investigated and gave higher SSCs than the modified
      fluorescence method. Further studies on the mechanism of norfloxacin accumulation
      by M. aurum were performed. An increase in the pH of the wash buffer from 7.0 to
      9.0 did not significantly affect the final SSC obtained. Accumulation was
      nonsaturated over a norfloxacin concentration range of 0 to 100 microg/ml, and
      the proton motive force inhibitor 2,4-dinitrophenol (1 and 2 mM), whether it was
      added before or after norfloxacin was added, had no effect on the final SSC
      obtained. 2,4-Dinitrophenol also had no effect on norfloxacin accumulation by M.
      smegmatis. Furthermore, norfloxacin accumulation by M. aurum was unaffected by
      the presence of either Tween 80 or subinhibitory concentrations of ethambutol in
      the growth medium. Therefore, it is proposed that norfloxacin accumulation by
      mycobacteria occurs by simple, energy-independent diffusion.

PMID- 9559788
TI  - Activity of amoxicillin-clavulanate against penicillin-resistant Streptococcus
      pneumoniae in an experimental respiratory infection model in rats.
AB  - High doses of amoxicillin, equivalent to those produced by 500- and 750-mg oral
      doses in humans (area under the plasma concentration-time curve), were effective
      against a penicillin-resistant strain of Streptococcus pneumoniae in an
      experimental respiratory tract infection in immunocompromised rats; this superior
      activity confirms the results of previous studies. An unexpected enhancement of
      amoxicillin's antibacterial activity in vivo against penicillin-resistant and 
      susceptible S. pneumoniae strains was observed when subtherapeutic doses of
      amoxicillin were coadministered with the beta-lactamase inhibitor potassium
      clavulanate. The reason for this enhancement was unclear since these organisms do
      not produce beta-lactamase. The differential binding of clavulanic acid and
      amoxicillin to penicillin-binding proteins may have contributed to the observed
      effects.

PMID- 9559787
TI  - Zidovudine pharmacokinetics in premature infants exposed to human
      immunodeficiency virus.
AB  - We used population analysis techniques to determine zidovudine (ZDV)
      pharmacokinetic parameters in 15 preterm neonates (mean gestational age, 29.4
      weeks; mean birth weight, 1,230 g) at a mean age of 5.5 days. The values of the
      pharmacokinetic parameters were as follows: clearance, 2.53 +/- 0.44 ml/min/kg;
      volume of distribution, 1.59 +/- 0.51 liters/kg; and half-life, 7.2 +/- 1.5 h.
      For seven infants studied a second time, at a mean age of 17.7 days, an increase
      in the mean clearance (2.33 versus 4.35 ml/min/kg; P = 0.024) and a decrease in
      the half-life (7.3 versus 4.4 h; P = 0.003) were found. The ZDV clearance is low
      and the half-life is prolonged in premature neonates, but the clearance increases
      and the half-life decreases with postnatal age. Potentially toxic concentrations
      may accumulate in serum if the standard dosage for full-term infants is used. We
      suggest that initial ZDV dosing should be reduced to 1.5 mg every 12 h for
      preterm neonates.

PMID- 9559789
TI  - In vitro evaluation of drug susceptibilities of Babesia divergens isolates.
AB  - The susceptibilities of three bovine and two human Babesia divergens isolates to
      antimicrobial agents were evaluated in vitro by a tritiated hypoxanthine
      incorporation assay. The MICs at which 50% of isolates are inhibited (MIC50s) for
      mefloquine (chlorhydrate), chloroquine (sulfate), quinine (chlorhydrate),
      clindamycin (phosphate), pentamidine (isethionate), phenamidine (isethionate)
      plus oxomemazine (chlorhydrate), lincomycin (chlorhydrate monohydrate), and
      imidocarb (dipropionate) were determined. Except for imidocarb, the MIC50s
      observed for the different isolates were close. Imidocarb and the combination of
      phenamidine plus oxomemazine exhibited the highest in vitro activity, while
      antimalarial agents such as mefloquine, choroquine, and quinine were inactive.
      Other drugs had intermediate activities. The data support further in vitro
      evaluation of antimicrobial agents active against B. divergens for the
      improvement of therapeutic strategies.

PMID- 9559791
TI  - Cefotaxime-resistant Enterobacteriaceae isolates from a hospital in Warsaw,
      Poland: identification of a new CTX-M-3 cefotaxime-hydrolyzing beta-lactamase
      that is closely related to the CTX-M-1/MEN-1 enzyme.
AB  - A group of cefotaxime-resistant Citrobacter freundii and Escherichia coli
      isolates were collected by a clinical laboratory in a hospital in Warsaw, Poland,
      in July 1996. Detailed analysis has shown that all of these produced a beta
      lactamase (pI, 8.4) belonging to the CTX-M family, one of the minor extended
      spectrum beta-lactamase families with a strong cefotaxime-hydrolyzing activity.
      Sequencing has revealed that C. freundii isolates produced a new CTX-M-3 enzyme
      which is very closely related to the CTX-M-1/MEN-1 beta-lactamase, sporadically
      identified in Europe over a period of 6 years. Amino acid sequences of these two
      beta-lactamases differ at four positions: Val77Ala, Asp114Asn, Ser140Ala, and
      Asn288Asp (the first amino acid of each pair refers to CTX-M-1/MEN-1 and second
      refers to CTX-M-3). The partial sequence of the E. coli CTX-M gene was identical
      to the corresponding region of bla(CTX-M-3), but a transconjugant of the E. coli
      isolate expressed higher levels of resistance to beta-lactams than did C.
      freundii transconjugants. These resistance differences correlated with
      differences in plasmid DNA restriction patterns. Our results suggest that CTX-M
      genes have been spread among different species of the family Enterobacteriaceae
      in the hospital and that the CTX-M-3-expressing C. freundii strain causing
      routine urinary tract infections has been maintained for a relatively long time
      in the hospital environment.

PMID- 9559790
TI  - Relationship between didanosine exposure and surrogate marker response in human
      immunodeficiency virus-infected outpatients.
AB  - We used information available from routine clinic visits to characterize the
      pharmacokinetics of didanosine in 82 human immunodeficiency virus-infected
      patients. A total of 271 blood samples were collected for the measurement of
      didanosine concentrations in plasma (mean +/- standard deviation [SD], 3.30 +/-
      2.21 samples/patient). Bayesian estimates of didanosine oral clearance (CL[oral])
      were obtained for these patients by the POSTHOC option within the NONMEM software
      package. Population priors from a previous NONMEM analysis of didanosine
      pharmacokinetics were used. The mean +/- SD CL(oral) was 132 +/- 27.7 liters/h,
      which agrees reasonably well with estimates obtained from previous
      pharmacokinetic studies of didanosine. Estimates of individual didanosine
      exposure were then used to consider potential relationships between drug exposure
      and surrogate marker response over a 6-month period. No correlations were found
      between the didanosine area under the concentration-time curve from 0 to 6 months
      and the absolute CD4 cell count (r = 0.305; 0.1 < P < 0.2), weight response (r =
      0.0857; P > 0.4), or percentage of CD4 lymphocytes (r = 0.0559; P > 0.4). Future
      efforts to characterize didanosine exposure in outpatients by random sampling
      methods should involve more directed efforts to limit residual variability in the
      data.

PMID- 9559793
TI  - Prophylaxis of acute osteomyelitis with absorbable ofloxacin-impregnated beads.
AB  - We investigated the use of an ofloxacin-impregnated bioabsorbable composite for
      the prevention of acute Staphylococcus aureus osteomyelitis. New Zealand White
      rabbits were anesthetized, the femur was exposed, and a cortical hole was
      drilled. Animals were randomly given drug-free composites or ofloxacin
      impregnated composites; the composites were placed at the site of injury, and the
      incision was closed. One hour later, all animals were intravenously inoculated
      with 5 x 10(4) CFU of S. aureus and observed for 28 days. Bone culture data
      revealed that S. aureus was isolated from 3 of 12 rabbits in the ofloxacin
      composite group and 9 of 11 animals in the control group (P = 0.02). Radiographic
      evaluation revealed that the drug-free group had a significantly (P = 0.01)
      greater degree of radiographic evidence of infection than the group given
      ofloxacin composites. Although a limited number of histologic samples were
      available, these data also paralleled the radiographic and culture data. This
      study demonstrates the effectiveness of the implantable ofloxacin bioabsorbable
      composites to prevent the development of acute osteomyelitis.

PMID- 9559792
TI  - Unique metabolism of a novel antiviral L-nucleoside analog, 2'-fluoro-5-methyl
      beta-L-arabinofuranosyluracil: a substrate for both thymidine kinase and
      deoxycytidine kinase.
AB  - 2'-Fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU) is the first L
      nucleoside analog with low cytotoxicity discovered to have potent antiviral
      activities against both hepatitis B virus and Epstein-Barr virus but not human
      immunodeficiency virus. This spectrum of activity is different from those of the
      other L-nucleoside analogs examined. L-FMAU enters cells through equilibrative
      sensitive and -insensitive nucleoside transport as well as through nonfacilitated
      passive diffusion. L-FMAU is phosphorylated stepwise in cells to its mono-, di-,
      and triphosphate forms. In the present study the enzymes responsible for the
      first step of L-FMAU phosphorylation were identified. This is the first thymidine
      analog shown to be a substrate not only for cytosolic thymidine kinase and
      mitochondrial deoxypyrimidine kinase but also for deoxycytidine kinase. This
      finding suggests that the antiviral activity of L-FMAU will not be limited by the
      loss or alteration of any of these deoxynucleoside kinases.

PMID- 9559794
TI  - Cyclosporin analogs inhibit in vitro growth of Cryptosporidium parvum.
AB  - Cyclosporine and nonimmunosuppressive cyclosporin (CS) analogs were demonstrated
      to be potent inhibitors of the growth of the intracellular parasite
      Cryptosporidium parvum in short-term (48-h) in vitro cultures. Fifty-percent
      inhibitory concentrations (IC50s) were 0.4 microM for SDZ 033-243, 1.0 microM for
      SDZ PSC-833, and 1.5 microM for cyclosporine. Two other analogs were less
      effective than cyclosporine: the IC50 of SDZ 205-549 was 5 microM, and that of
      SDZ 209-313 was 7 microM. These were much lower than the IC50 of 85 microM of
      paromomycin, a standard positive control for in vitro drug assays for this
      parasite. In addition, intracellular growth of excysted sporozoites that had been
      incubated for 1 h in cyclosporine was significantly reduced, suggesting that the
      drug can inhibit sporozoite invasion. The cellular activities of the CS analogs
      used have been characterized for mammalian cells and protozoa. The two analogs
      that were most active in inhibiting C. parvum, SDZ PSC-833 and SDZ 033-243, bind
      weakly to cyclophilin, a peptidyl proline isomerase which is the primary target
      of cyclosporine and CS analogs. However, they are potent modifiers of the
      activity of the P glycoproteins/ multidrug resistance (MDR) transporters, members
      of the ATP-binding cassette (ABC) superfamily. Hence, both cyclophilin and some
      ABC transporters may be targets for this class of drugs, although drugs that
      preferentially interact with the latter are more potent. Cyclosporine (0.5
      microM) had no significant chemosensitizing activity. That is, it did not
      significantly increase sensitivity to paromomycin, suggesting that an ABC
      transporter is not critical in the efflux of this drug. Cyclosporine at
      concentrations up to 50 microM was not toxic to host Caco-2 cells in the
      CellTiter 96 assay. The results of this study complement those of studies of the
      inhibitory effect of cyclosporine and CS analogs on other apicomplexan parasites,
      Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii.

PMID- 9559795
TI  - Population pharmacokinetic study of amikacin administered once or twice daily to
      febrile, severely neutropenic adults.
AB  - Once-daily (o.d.) administration of 20 mg of amikacin per kg of body weight to
      neutropenic patients has been validated by clinical studies, but amikacin
      pharmacokinetics have been documented only for the 7.5-mg/kg twice-daily (b.i.d.)
      regimen in this population. In order to determine in neutropenic patients (i) the
      influence of the dosing regimen on the kinetics of amikacin, (ii) the linearity
      of kinetics of amikacin in the range of 7.5 to 20 mg/kg, and (iii) the influence
      of patient characteristics on the disposition of amikacin and (iv) to provide a
      rationale for dosing recommendations, we evaluated the population
      pharmacokinetics of amikacin administered to 57 febrile neutropenic adults
      (neutrophil count, <500/mm3) being treated for a hematological disorder and
      receiving amikacin at 7.5 mg/kg b.i.d. (n = 29) or 20 mg/kg o.d. (n = 28) and
      administered intravenously over 0.5 h. A total of 278 blood samples were obtained
      (1 to 14 samples per patient) during one or several administration intervals (1
      to 47). Serum amikacin levels were measured by the enzyme-multiplied immunoassay
      technique. A mixed-effect modeling approach was used to fit a bicompartmental
      model to the data (NONMEM software). The influences of the dosing regimen and the
      demographic and biological indices on the pharmacokinetic parameters of amikacin
      were evaluated by the maximum-likelihood ratio test on the population model. The
      dosing regimen had no influence on amikacin pharmacokinetic parameters, i.e., the
      kinetics of amikacin were linear over the range of 7.5 to 20 mg/kg. Amikacin
      elimination clearance (CL) was only correlated with creatinine clearance or its
      covariates, namely, sex, age, body weight, and serum creatinine level. The
      interindividual variability of CL was 21%, while those of the central volume of
      distribution, the distribution clearance, and the tissue volume of distribution
      were 15, 30, and 25%, respectively. On the basis of the expected distribution of
      amikacin concentrations in this population, dosing recommendations as a function
      of creatinine clearance (CL[CR]) are proposed: for patients with normal renal
      function (CL[CR] of 80 to 130 ml/min), 20 mg/kg o.d. is recommended, whereas for
      patients with severe renal impairment (CL[CR], 10 to 20 ml/min), a dosage of 17
      mg/kg every 48 h is recommended.

PMID- 9559796
TI  - Activities and time-kill studies of selected penicillins, beta-lactamase
      inhibitor combinations, and glycopeptides against Enterococcus faecalis.
AB  - The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin
      clavulanate, ampicillin, ampicillin-sulbactam, vancomycin, and teicoplanin were
      tested against 212 Enterococcus faecalis strains (9 beta-lactamase producers) by
      standard agar dilution MIC testing (10[4] CFU/spot). The MICs at which 50 and 90%
      of the isolates were inhibited (MIC50s and MIC90s, respectively) were as follows
      (microg/ml): piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8;
      ticarcillin, 64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and
      2; ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin, 0.5 and
      1. Agar dilution MIC testing of the nine beta-lactamase-positive strains with an
      inoculum of 10(6) CFU/spot revealed higher beta-lactam MICs (piperacillin, 64 to
      >256 microg/ml; ticarcillin, 128 to >256 microg/ml; and ampicillin, 16 to 128
      microg/ml); however, MICs with the addition of inhibitors were similar to those
      obtained with the lower inoculum. Time-kill studies of 15 strains showed that
      piperacillin-tazobactam was bactericidal (99.9% killing) for 14 strains after 24
      h at four times the MIC, with 90% killing of all 15 strains at two times the MIC.
      After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at
      two times the MIC. Ampicillin gave 99.9% killing of 14 beta-lactamase-negative
      strains after 24 h at eight times the MIC, with 90% killing of all 15 strains at
      two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains,
      respectively, was found at two times the MIC. Killing by ticarcillin-clavulanate
      was slower than that observed for piperacillin-tazobactam, relative to the MIC.
      For the one beta-lactamase-producing strain tested by time-kill analysis with a
      higher inoculum, addition of the three inhibitors (including sulbactam) to each
      of the beta-lactams resulted in bactericidal activity at 24 h at two times the
      MIC. For an enzyme-negative strain, addition of inhibitors did not influence
      kinetics. Kinetics of vancomycin and teicoplanin were significantly slower than
      those of the beta-lactams, with bactericidal activity against 6 strains after 24
      h at eight times the MIC, with 90% killing of 12 and 14 strains, respectively, at
      four times the MIC. Slower-kill kinetics by both glycopeptides were observed at
      earlier periods.

PMID- 9559797
TI  - Efficacy of trovafloxacin against penicillin-susceptible and multiresistant
      strains of Streptococcus pneumoniae in a mouse pneumonia model.
AB  - The increasing emergence of penicillin-resistant and multidrug-resistant strains
      of Streptococcus pneumoniae will create a serious therapeutic problem in coming
      years. Trovafloxacin is a novel naphthyridone quinolone with promising activity
      against S. pneumoniae, including penicillin-resistant strains (MIC for 90% of the
      isolates tested, 0.25 microg/ml). We compared its in vivo efficacy with that of
      other fluoroquinolones (ciprofloxacin, temafloxacin, and sparfloxacin) and a
      reference beta-lactam (amoxicillin) in a model of acute experimental pneumonia.
      Immunocompetent Swiss mice were infected by peroral tracheal delivery of a
      virulent, penicillin-susceptible strain (MIC, 0.03 microg/ml); leukopenic Swiss
      mice were infected with three poorly virulent, penicillin-resistant strains
      (MICs, 4 to 8 microg/ml) and a ciprofloxacin-resistant strain (MIC, 32
      microg/ml). Treatments were started 6 h (immunocompetent mice) or 3 h (leukopenic
      mice) after infection. Doses ranging from 12.5 to 300 mg/kg were given at 12- or
      8-h intervals for 3 days. Trovafloxacin (25 mg/kg) was the most effective agent
      in vivo against penicillin-susceptible and -resistant strains. Corresponding
      survival rates were 2- to 4-fold higher than with 50-mg/kg sparfloxacin or
      temafloxacin and 8- to 16-fold higher than with 100-mg/kg ciprofloxacin. The
      ratios of the area under the concentration-time curve to the MIC in serum and
      lung tissue were more favorable with trovafloxacin than with the other
      quinolones. Efficacy in vivo correlated with pharmacokinetic parameters.
      Trovafloxacin shows potential for the treatment of infections due to penicillin
      susceptible and -resistant S. pneumoniae but appears to be ineffective against a
      ciprofloxacin-resistant strain.

PMID- 9559798
TI  - Survey of resistance of herpes simplex virus to acyclovir in northwest England.
AB  - Acyclovir (ACV) has been used for more than 15 years in the management of herpes
      simplex virus (HSV) and varicella-zoster virus (VZV) disease. The present survey
      was undertaken to assess the level of ACV resistance in the population. More than
      2,000 HSV isolates from both immunocompetent and immunocompromised patients in
      northwest England were collected over a 2-year period and tested for sensitivity
      to ACV. These studies suggested a prevalence of resistance of approximately 0.1
      to 0.6% in immunocompetent individuals, with no apparent difference in prevalence
      between treated and untreated groups. In line with previous studies, the
      prevalence of resistance in treated immunocompromised individuals was
      approximately 6%.

PMID- 9559799
TI  - Efficacy of LY303366 against amphotericin B-susceptible and -resistant
      Aspergillus fumigatus in a murine model of invasive aspergillosis.
AB  - LY303366 is a novel antifungal echinocandin with excellent in vitro activity
      against Aspergillus spp. We compared four doses (1, 2.5, 10, and 25 mg/kg of body
      weight) of LY303366 with amphotericin B (0.5 to 5 mg/kg) in a temporarily
      neutropenic murine model of invasive aspergillosis against an amphotericin B
      susceptible (AF210) and an amphotericin B-resistant (AF65) Aspergillus fumigatus
      isolate based on in vivo response. Mice were immunosuppressed with
      cyclophosphamide (200 mg/kg) and infected 3 days later. Treatment started 18 h
      after infection and lasted for 10 days. LY303366 was given once daily
      intravenously for 10 days, and amphotericin B (at 0.5, 2, and 5 mg/kg) was given
      once daily intraperitoneally for 10 days, or only on days 1, 2, 4, and 7 (at 5
      mg/kg). Kidneys and lungs from survivors were cultured on day 11. Control mice in
      both experiments had 90 to 100% mortality. Amphotericin B at 0.5 mg/kg and
      LY303366 at 1 mg/kg yielded 10 to 20% survival rates for mice infected with
      either AF210 or AF65. Amphotericin B at 2 and 5 (both regimens) mg/kg yielded a
      70 to 100% survival rate for mice infected with AF210 but a 10 to 30% survival
      rate for mice infected with AF65 (P = 0.01 to 0.04 compared with AF210). Against
      AF210 and AF65, LY303366 at 2.5, 10, and 25 mg/kg produced a survival rate of 70
      to 80%, which was as effective as amphotericin B for AF210, but superior to
      amphotericin B for AF65 (P < 0.03 to 0.0006). For AF65, LY303366 at 10 and 25
      mg/kg/day was superior to amphotericin B at 2 and 5 mg/kg/day in reducing tissue
      colony counts (P = 0.01 to 0.003), and for AF210, amphotericin B at 5 mg/kg/day
      and at 5 mg/kg in four doses was more effective than all four regimens of
      LY303366 in reducing renal culture counts (P = 0.01 to 0.0001). The present study
      shows, for the first time, that in vivo resistance of A. fumigatus to
      amphotericin B exists, although this could not be detected by in vitro
      susceptibility assays. Furthermore, LY303366 appears to be effective against
      amphotericin B-susceptible and -resistant A. fumigatus infection in this model
      and should be further evaluated clinically.

PMID- 9559800
TI  - Discriminatory detection of inhibitor-resistant beta-lactamases in Escherichia
      coli by single-strand conformation polymorphism-PCR.
AB  - Plasmid-mediated mechanisms, comprising TEM hyperproduction, TEM derivative
      production, and OXA production, lead to amoxicillin-clavulanic acid resistance in
      enterobacteria. The ability of the single-strand conformation polymorphism (SSCP)
      PCR method to differentiate the genes encoding inhibitor-resistant beta
      lactamases was evaluated with three bla(TEM) primer pairs. The bla(TEM) genes,
      which were known to be different on the basis of their nucleotide sequences
      (bla[TEM-1A], bla[TEM-1B], bla[TEM-2], bla[TEM-30], bla[TEM-32], and bla[TEM
      35]), were identified as different by their electrophoretic mobilities. The
      bla(TEM-33), bla(TEM-34), bla(TEM-36), bla(TEM-37), bla(TEM-38), and bla(TEM-39)
      genes, whose sequence differences have been established by oligotyping, displayed
      different SSCP profiles for different fragments, suggesting genetic differences
      in addition to those defined by oligotyping. Confirmed by sequencing, these
      additional genetic events concerned silent mutations at certain positions and,
      notably, a G-->T transversion at position 1 of the -10 consensus sequence in
      bla(TEM-34), bla(TEM-36), bla(TEM-37), and bla(TEM-39). Applied to eight clinical
      isolates of Escherichia coli resistant to amoxicillin-clavulanic acid, the SSCP
      method detected TEM-1 in three strains and TEM-30, TEM-32, and TEM-35 in three
      other strains, respectively. A novel TEM derivative (TEM-58) was detected in
      another strain, and the deduced amino acid sequence showed two substitutions:
      Arg244Ser, which is known to confer amoxicillin-clavulanic acid resistance in TEM
      30, and Val261Ile, which has not been described previously. The eighth strain
      produced an OXA beta-lactamase. Given the discriminatory power and the
      applicability of SSCP-PCR, this method can be proposed as a means of following
      the evolution of the frequencies of the different inhibitor-resistant beta
      lactamases.

PMID- 9559801
TI  - Double-blind evaluation of the safety and pharmacokinetics of multiple oral once
      daily 750-milligram and 1-gram doses of levofloxacin in healthy volunteers.
AB  - The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy
      male volunteers were investigated in a randomized, double-blind, placebo
      controlled study. Subjects were randomly assigned to the treatment (n = 10) or
      placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was
      administered orally as a single dose on day 1, followed by a washout period on
      days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period,
      1 g of levofloxacin or a placebo was administered in a similar fashion in period
      2. Plasma and urine levofloxacin concentrations were measured by high-pressure
      liquid chromatography. Pharmacokinetic parameters were estimated by model
      independent methods. Levofloxacin was rapidly absorbed after single and multiple
      once-daily 750-mg and 1-g doses with an apparently large volume of distribution.
      Peak plasma levofloxacin concentration (Cmax) values were generally attained
      within 2 h postdose. The mean values of Cmax and area under the concentration
      time curve from 0 to 24 h (AUC0-24) following a single 750-mg dose were 7.1
      microg/ml and 71.3 microg x h/ml, respectively, compared to 8.6 microg/ml and
      90.7 microg x h/ml, respectively, at steady state. Following the single 1-g dose,
      mean Cmax and AUC0-24 values were 8.9 microg/ml and 95.4 microg x h/ml,
      respectively; corresponding values at steady state were 11.8 microg/ml and 118
      microg x h/ml. These Cmax and AUC0-24 values indicate modest and similar degrees
      of accumulation upon multiple dosing at the two dose levels. Values of apparent
      total body clearance (CL/F), apparent volume of distribution (Vss/F), half-life
      (t1/2), and renal clearance (CL[R]) were similar for the two dose levels and did
      not vary from single to multiple dosing. Mean steady-state values for CL/F,
      Vss/F, t1/2, and CL(R) following 750 mg of levofloxacin were 143 ml/min, 100
      liters, 8.8 h, and 116 ml/min, respectively; corresponding values for the 1-g
      dose were 146 ml/min, 105 liters, 8.9 h, and 105 ml/min. In general, the
      pharmacokinetics of levofloxacin in healthy subjects following 750-mg and 1-g
      single and multiple once-daily oral doses appear to be consistent with those
      found in previous studies of healthy volunteers given 500-mg doses. Levofloxacin
      was well tolerated at either high dose level. The most frequently reported drug
      related adverse events were nausea and headache.

PMID- 9559802
TI  - Use of a rapid throughput in vivo screen to investigate inhibitors of eukaryotic
      topoisomerase II enzymes.
AB  - Topoisomerase II catalyzes the passage of one DNA helix through another via a
      transient double-stranded break. The essential nature of this enzyme in cell
      proliferation and its mechanism of action make it an ideal target for cytotoxic
      agents. Saccharomyces cerevisiae topoisomerase II has been frequently used as a
      model for testing potential inhibitors of eukaryotic topoisomerase II as
      antitumor agents. The standard in vivo method of estimating the sensitivity of S.
      cerevisiae to the antitopoisomerase drugs is via inhibition or kill curves which
      rely on viable-cell counts and is labor intensive. We present an alternative to
      this, a high-throughput in vivo screen. This method makes use of a drug-permeable
      S. cerevisiae strain lacking endogenous topoisomerase II, which is modified to
      express either human topoisomerase IIalpha or IIbeta or S. cerevisiae
      topoisomerase II carried on plasmids. Each modified strain expresses a full
      length topoisomerase II enzyme, as opposed to the more commonly used temperature
      sensitive S. cerevisiae mutant expressing yeast or yeast/human hybrid enzymes. A
      comparison of this new method with a plating-and-counting method gave similar
      drug sensitivity results, with increased accuracy and reduced manual input for
      the new method. The information generated has highlighted the sensitivities of
      different topoisomerase II enzymes and isoenzymes to several different classes of
      topoisomerase II inhibitor.

PMID- 9559803
TI  - Impact of bacterial biofilm formation on in vitro and in vivo activities of
      antibiotics.
AB  - The impact of bacterial adherence on antibiotic activity was analyzed with two
      isogenic strains of Staphylococcus epidermidis that differ in the features of
      their in vitro biofilm formation. The eradication of bacteria adhering to glass
      beads by amikacin, levofloxacin, rifampin, or teicoplanin was studied in an
      animal model and in a pharmacokinetically matched in vitro model. The features of
      S. epidermidis RP62A that allowed it to grow on surfaces in multiple layers
      promoted phenotypic resistance to antibiotic treatment, whereas strain M7 failed
      to accumulate, despite initial adherence on surfaces and growth in suspension
      similar to those for RP62A. Biofilms of S. epidermidis M7 were better eradicated
      than those of strain RP62A in vitro (46 versus 31%; P < 0.05) as well as in the
      animal model (39 versus 9%; P < 0.01).

PMID- 9559804
TI  - Comparison of fungizone, Amphotec, AmBisome, and Abelcet for treatment of
      systemic murine cryptococcosis.
AB  - Three lipid-based formulations of amphotericin B have been approved for use in
      various countries. The aim of this study was to compare Amphotec (ABCD; Sequus),
      AmBisome (AmBi; Nexstar), Abelcet (ABLC; The Liposome Co.), and conventional
      deoxycholate amphotericin B (Fungizone; Bristol Meyers Squibb) for the treatment
      of experimental systemic cryptococcosis. A model was established in 10-week-old
      female CD-1 mice by intravenous (i.v.) injection of 6.25 x 10(5) viable
      Cryptococcus neoformans yeast cells. Therapy began 4 days later, with i.v.
      administration three times per week for 2 weeks. Mice received either no
      treatment, 1 mg of Fungizone per kg of body weight, or 1, 5, or 10 mg of ABCD,
      AmBi, or ABLC per kg. Ninety percent of control mice died between days 15 and 34.
      All treatment regimens except ABLC at 1 mg/kg prolonged survival compared with no
      treatment (P < 0.01 to 0.001). All mice receiving 5 or 10 mg of ABCD or AmBi per
      kg and 90% of mice given 10 mg of ABLC per kg survived, whereas < or =50% of
      those given other treatment regimens survived. Fungizone was the least effective
      of the four formulations, with 5 or 10 mg of ABCD, AmBi, or ABLC per kg resulting
      in a significantly better outcome than Fungizone (P < 0.001). Among the three
      formulations, ABCD and AmBi were equally effective, both being better than ABLC
      at equal 5- or 10-mg/kg doses (P < 0.001). Comparison of residual infectious
      burdens in various organs showed that each drug had some dose-responsive efficacy
      in three or more organs at escalating doses. In the brain, ABCD or AmBi at 5 or
      10 mg/kg or ABLC at 10 mg/kg was more effective than Fungizone at 1 mg/kg or no
      treatment, while ABCD or AmBi at 1 mg/kg was as effective as ABLC at 10 mg/kg.
      Similar results were obtained for the kidneys and lungs. In the spleen, ABCD at
      10 mg/kg cured all mice of infection and was superior to all other regimens. In
      the liver, AmBi at 5 mg/kg was superior to an equal dose of ABCD or ABLC.
      Overall, the efficacies of ABCD and AmBi were equal to that of Fungizone at 1
      mg/kg and were about 10-fold better than that of ABLC, particularly in the brain;
      a comparative rank order of efficacies was ABCD approximately equal to AmBi >
      ABLC >> Fungizone. This is the first study that compared all four amphotericin B
      formulations.

PMID- 9559805
TI  - Pharmacokinetics of two multiple-dosing regimens of D0870 in human
      immunodeficiency virus-positive patients: a phase I study.
AB  - D0870 is a triazole with a broad antifungal spectrum, and it has been shown to
      have both in vitro and in vivo activities against wild-type and fluconazole
      resistant strains of Candida albicans. Twenty-two human immunodeficiency virus
      (HIV)-positive male subjects were enrolled in an open, nonrandomized trial
      investigating the pharmacokinetics of two different dosing regimens of D0870 and
      assessing the safety of multiple oral doses of D0870 in HIV-positive subjects and
      their ability to tolerate multiple oral doses. Nine subjects received an initial
      loading dose of 50 mg, followed by four once-daily maintenance doses of 10 mg. A
      further nine subjects received an initial 200-mg loading dose followed by four
      daily maintenance doses of 25 mg. All subjects were fasting. A single loading
      dose of 50 mg of D0870 resulted in a mean maximum concentration in serum (Cmax)
      of 107 +/- 32 ng/ml. Concentrations in plasma were maintained by the 10-mg once
      daily dosing regimen as seen by the similar values of the area under the
      concentration-time curve from 0 to 24 h following dosing on days 1 and 5 and a
      mean accumulation ratio close to unity (0.90). The terminal plasma half-life of
      D0870 in plasma following dosing on day 5 ranged from 23 to 85 h (mean, 49 h). A
      single loading dose of 200 mg of D0870 resulted in a Cmax of 431 +/- 186 ng/ml.
      Concentrations in plasma were again maintained by the 25-mg daily dosing regimen,
      with the mean accumulation ratio being close to unity (1.17). The terminal half
      life of D0870 in plasma following dosing on day 5 of phase II of the study ranged
      from 34 to 137 h (mean, 71 h). In addition, the concentrations achieved in the
      plasma of these HIV-positive subjects were similar to the values predicted from
      simulations based on data derived from normal, healthy subjects. D0870 was well
      tolerated. No serious adverse events were experienced during the course of the
      study, and all volunteers completed the trial. A total of 15 adverse events were
      reported, but none were considered to be related to the administration of D0870
      and all had resolved by the end of the trial. No changes in the hematology,
      clinical chemistry, or urinalysis parameters were considered to be related to
      dosing with D0870. No clinically significant changes in the electrocardiogram
      parameters were noted during the trial. The data generated in this trial support
      further investigation of these regimens with HIV-positive subjects with
      fluconazole-susceptible or -resistant oropharyngeal candidosis.

PMID- 9559807
TI  - Synthesis and antibacterial evaluation of novel water-soluble organic peroxides.
AB  - A set of new water-soluble organic peroxides has been synthesized and evaluated
      for in vitro antibacterial activity as part of an effort to develop new
      antibacterial agents for the treatment of acne vulgaris. The water solubility of
      these new dialkyl peroxides and peroxyesters was achieved by incorporating either
      a quaternary ammonium group or a polyethylene glycol moiety. These peroxides are
      effective against both gram-positive and gram-negative bacteria and have a
      prolonged activity compared to that of benzoyl peroxide and other peroxide-type
      antiseptic agents. Among them 4-[[(tert
      butylperoxy)carbonyl]benzyl]triethylammonium chloride and [10-(tert
      butylperoxy)decyl]trimethylammonium bromide have the broadest antimicrobial
      spectrums. We have shown that the oxidizing properties of the dioxy group of
      these compounds are responsible for their antibacterial activities.

PMID- 9559806
TI  - Activity of voriconazole, a new triazole, combined with neutrophils or monocytes
      against Candida albicans: effect of granulocyte colony-stimulating factor and
      granulocyte-macrophage colony-stimulating factor.
AB  - The antifungal activity of voriconazole (VCZ) was tested against Candida albicans
      in the absence or presence of polymorphonuclear neutrophils (PMN) or monocytes.
      In some experiments, VCZ was compared to fluconazole (FCZ). On a weight basis,
      VCZ was 10-fold more efficacious than FCZ against C. albicans Sh27. Against an
      FCZ-resistant isolate, VCZ at 1 microg/ml produced the same fungistasis as FCZ at
      20 microg/ml. VCZ at 0.1 microg/ml collaborated with PMN for enhanced killing to
      the same extent as FCZ at 1.0 microg/ml. Granulocyte-colony-stimulating factor (G
      CSF) enhanced the candidacidal activity of PMN, and it increased the
      collaboration of PMN with VCZ for killing. Granulocyte-macrophage (GM)-CSF also
      significantly enhanced both the killing by PMN and the collaboration of PMN with
      VCZ for killing. VCZ collaborated with GM-CSF-activated monocytes [corrected] for
      enhanced killing of C. albicans Sh27, and GM-CSF increased this collaboration.
      Taken together, these data show that VCZ is more potent than FCZ against C.
      albicans isolates, alone and in collaboration with PMN or monocytes for enhanced
      killing. In addition, G-CSF- or GM-CSF-activated PMN and monocytes have enhanced
      collaboration with VCZ compared to that of unstimulated phagocytes with VCZ.

PMID- 9559808
TI  - Dual inhibition of human rhinovirus 2A and 3C proteases by homophthalimides.
AB  - The 2A and 3C proteases encoded by human rhinoviruses (HRVs) are attractive
      targets for antiviral drug development due to their important roles in viral
      replication. Homophthalimides were originally identified as inhibitors of
      rhinovirus 3C protease through our screening effort. Previous studies have
      indicated that the antiviral activity of certain homophthalimides exceeded their
      in vitro inhibitory activity against the viral 3C protease, suggesting that an
      additional mechanism might be involved. Reported here is the identification of
      homophthalimides as potent inhibitors for another rhinovirus protease, designated
      2A. Several homophthalimides exhibit time-dependent inhibition of the 2A protease
      in the low-micromolar range, and enzyme-inhibitor complexes were identified by
      mass spectrometry. Compound LY343814, one of the most potent inhibitors against
      HRV14 2A protease, had an antiviral 50% inhibitory concentration of 4.2 microM in
      the cell-based assay. Our data reveal that homophthalimides are not only 3C but
      also 2A protease inhibitors in vitro, implying that the antiviral activity
      associated with these compounds might result from inactivation of both 2A and 3C
      proteases in vivo. Since the processing of the viral polyprotein is hierarchical,
      dual inhibition of the two enzymes may result in cooperative inhibition of viral
      replication. On the basis of the current understanding of their enzyme inhibitory
      mechanism, homophthalimides, as a group of novel nonpeptidic antirhinovirus
      agents, merit further structure-action relationship studies.

PMID- 9559809
TI  - Overexpression, purification, and characterization of the cloned metallo-beta
      lactamase L1 from Stenotrophomonas maltophilia.
AB  - The metallo-beta-lactamase L1 from Stenotrophomonas maltophilia was cloned,
      overexpressed, and characterized by spectrometric and biochemical techniques.
      Results of metal analyses were consistent with the cloned enzyme having 2 mol of
      tightly bound Zn(II) per monomer. Gel filtration chromatography demonstrated that
      the cloned enzyme exists as a tightly held tetramer with a molecular mass of ca.
      115 kDa, and matrix-assisted laser desorption ionization and time-of-flight mass
      spectrometry indicated a monomeric molecular mass of 28.8 kDa. Steady-state
      kinetic studies with a number of diverse penicillin and cephalosporin antibiotics
      demonstrated that L1 effectively hydrolyzes all tested compounds, with k(cat)/Km
      values ranging between 0.002 and 5.5 microM(-1) s(-1). These characteristics of
      the recombinant enzyme are contrasted to those previously reported for metallo
      beta-lactamases isolated directly from S. maltophilia.

PMID- 9559810
TI  - Effect of grapefruit juice on clarithromycin pharmacokinetics.
AB  - To investigate whether grapefruit juice inhibits the metabolism of
      clarithromycin, 12 healthy subjects were given water or grapefruit juice before
      and after a clarithromycin dose of 500 mg in a randomized crossover study.
      Administration of grapefruit juice increased the time to peak concentration of
      both clarithromycin (82 +/- 35 versus 148 +/- 83 min; P = 0.02) and 14
      hydroxyclarithromycin (84 +/- 38 min versus 173 +/- 85; P = 0.01) but did not
      affect other pharmacokinetic parameters.

PMID- 9559811
TI  - Fluconazole pharmacokinetics in burn patients.
AB  - The pharmacokinetics of fluconazole in nine adult patients with severe (30 to 95%
      total body surface area) burns were studied. There was no significant difference
      in half-life (t1/2), clearance (CL), or volume of distribution (V) over time in
      five patients on days 3 and 8 of the study (P > 0.05). Combined parameter
      estimates (means +/- standard deviations) for all nine patients for the two study
      periods were as follows: t1/2, 24.4 +/- 5.8 h; CL, 0.36 +/- 0.09 ml/min/kg; and
      V, 0.72 +/- 0.12 liters/kg. These estimates of t1/2 and CL in burn patients were
      approximately 13% shorter and 30% more rapid, respectively, than the most extreme
      estimates reported for other populations.

PMID- 9559812
TI  - Efficacy of sulfamethoxypyridazine in a murine model of Pneumocystis carinii
      pneumonia.
AB  - Sulfamethoxazole is the component of co-trimoxazole responsible for its efficacy
      against Pneumocystis carinii pneumonia, but this drug is associated with frequent
      adverse effects. Sulfamethoxypyridazine is significantly more effective than
      sulfamethoxazole against a murine model of P. carinii and might be a candidate
      for testing in infected patients.

PMID- 9559813
TI  - Increased overall antibiotic susceptibility in Staphylococcus aureus femAB null
      mutants.
AB  - The staphylococcal pentaglycine side chain of the peptidoglycan is reduced to one
      glycine in femAB null mutants. This is associated with increased susceptibility
      to methicillin and to a whole range of unrelated antibiotics as well. Genetic
      evidence suggests that femAB null mutants are only viable because of a
      compensatory mutation in an unlinked site.

PMID- 9559814
TI  - Effects of slime produced by clinical isolates of coagulase-negative
      staphylococci on activities of various antimicrobial agents.
AB  - A novel in vitro semiquantitative method was developed to investigate the
      influence of staphylococcal slime on the activities of 22 antimicrobial agents.
      Pefloxacin, teicoplanin, and vancomycin demonstrated remarkable decreases in
      efficacy: 30, 52, and 63%, respectively. The activity of rifampin was not
      significantly reduced (0.99%), whereas all other agents tested were modestly
      affected (<15% decrease). These data could be influential in the treatment of
      implant-associated infections caused by slime-producing staphylococci.

PMID- 9559815
TI  - Comparative in vitro killing activities of meropenem, imipenem, ceftriaxone, and
      ceftriaxone plus vancomycin at clinically achievable cerebrospinal fluid
      concentrations against penicillin-resistant Streptococcus pneumoniae isolates
      from children with meningitis.
AB  - The activities of meropenem, imipenem, ceftriaxone, and vancomycin were evaluated
      against 80 penicillin-susceptible and -resistant Streptococcus pneumoniae
      strains. Meropenem, imipenem, ceftriaxone, and vancomycin MICs at which 90% of
      the isolates are inhibited were 0.5, 0.25, 1, and 0.25 microg/ml, respectively.
      Against penicillin-resistant strains, the best killing activity at cerebrospinal
      fluid concentrations was obtained with imipenem and ceftriaxone-vancomycin.
      However, while the killing activity of imipenem was significantly greater than
      that of meropenem, no significant difference was observed between the activities
      of meropenem and ceftriaxone-vancomycin.

PMID- 9559816
TI  - Antipneumococcal activities of a ketolide (HMR 3647), a streptogramin
      (quinupristin-dalfopristin), a macrolide (erythromycin), and a lincosamide
      (clindamycin).
AB  - Four different compounds belonging to the macrolide-lincosamide-streptogramin B
      (MLSb) class of antimicrobial agents were tested against 611 Streptococcus
      pneumoniae strains. The ketolide (HMR 3647, previously RU66647) and the
      streptogramin (quinupristin-dalfopristin) were both active against pneumococci
      with high-level MLSb resistance (clindamycin-resistant strains) as well as those
      with low-level macrolide resistance (clindamycin-susceptible strains).

PMID- 9559817
TI  - Ribosomes from an oxazolidinone-resistant mutant confer resistance to eperezolid
      in a Staphylococcus aureus cell-free transcription-translation assay.
AB  - Oxazolidinone-resistant mutants of Staphylococcus aureus, isolated with a spiral
      plating technique, had a 16-fold higher MIC (2 versus 32 microg/ml) of eperezolid
      when compared to the parental sensitive strain. Eperezolid inhibited in vitro
      protein translation with 50% inhibitory concentrations of 30 microM for the
      oxazolidinone-sensitive S30 extract and 75 microM for the resistant extract.
      Experiments mixing various combinations of S100 and crude ribosome preparations
      from oxazolidinone-sensitive and -resistant S. aureus strains in a transcription
      translation assay demonstrated that the resistant determinant resided within the
      ribosomal fraction. Ribosomes from the oxazolidinone-resistant strain bound less
      drug than ribosomes from the sensitive strain, indicating that the ribosome is
      the site of action for the oxazolidinones. These experiments demonstrate that an
      alteration of the ribosome is responsible for some or all of the oxazolidinone
      resistance observed in the S. aureus mutant.

PMID- 9559818
TI  - In vitro activity of a new 8-methoxyquinolone, BAY 12-8039, against Chlamydia
      pneumoniae.
AB  - The in vitro susceptibilities of 10 strains of Chlamydia pneumoniae to a new 8
      methoxyquinolone, BAY 12-8039, and to ofloxacin, doxycycline, and erythromycin
      were determined. The activity of BAY 12-8039 was similar to that of ofloxacin,
      with a MIC at which 90% of the isolates had no inclusions and a minimal
      chlamydicidal concentration at which 90% of the isolates had no inclusions after
      passage of 1.0 microg/ml, but this activity was less than those of doxycycline
      and erythromycin.

PMID- 9559819
TI  - Determination of activities of levofloxacin, alone and combined with gentamicin,
      ceftazidime, cefpirome, and meropenem, against 124 strains of Pseudomonas
      aeruginosa by checkerboard and time-kill methodology.
AB  - A total of 124 Pseudomonas aeruginosa strains were tested for synergy between
      levofloxacin and cefpirome, ceftazidime, gentamicin, and meropenem. Checkerboards
      yielded synergistic fractional inhibitory concentration (FIC) indices (< or =0.5)
      with 25 of 496 possible combinations. All other FIC indices were >0.5 to 2
      (additive or indifferent), with no antagonism. Time-kill studies with 12 strains
      showed that levofloxacin (0.06 to 0.5 microg/ml) was synergistic with cefpirome,
      ceftazidime, gentamicin, and meropenem in 10, 9, 4, and 11 strains, respectively.

PMID- 9559820
TI  - Killing of Staphylococcus aureus by C-8-methoxy fluoroquinolones.
AB  - C-8-methoxy fluoroquinolones were more lethal than C-8-bromine, C-8-ethoxy, and C
      8-H derivatives for Staphylococcus aureus, especially when topoisomerase IV was
      resistant. The methoxy group also increased lethality against wild-type cells
      when protein synthesis was inhibited. These properties encourage refinement of C
      8-methoxy fluoroquinolones to kill staphylococci.

PMID- 9559822
TI  - Transferable, plasmid-mediated vanB-type glycopeptide resistance in Enterococcus
      faecium.
AB  - An approximately 60-kb transferable, vanB-carrying plasmid has been identified in
      a clinical Enterococcus faecium strain. A similar plasmid has been observed in an
      unrelated E. faecium strain, suggesting that plasmid transfer of vanB operons
      occurs in nature and plays a role in the dissemination of VanB-type resistance
      among strains of E. faecium.

PMID- 9559821
TI  - Mutations in aarE, the ubiA homolog of Providencia stuartii, result in high-level
      aminoglycoside resistance and reduced expression of the chromosomal
      aminoglycoside 2'-N-acetyltransferase.
AB  - The aarE1 allele was identified on the basis of the resulting phenotype of
      increased aminoglycoside resistance. The aarE1 mutation also resulted in a small
      colony phenotype and decreased levels of aac(2')-Ia mRNA. The deduced AarE gene
      product displayed 61% amino acid identity to the Escherichia coli UbiA protein,
      an octaprenyltransferase required for the second step of ubiquinone biosynthesis.
      Complementation experiments in both Providencia stuartii and E. coli demonstrated
      that aarE and ubiA are functionally equivalent.

PMID- 9559824
TI  - In vitro and in vivo antidermatophyte activities of NND-502, a novel optically
      active imidazole antimycotic agent.
AB  - In vitro and in vivo antidermatophyte activities of NND-502, a new imidazole
      antimycotic agent, were compared with those of two existing antifungal agents,
      lanoconazole and terbinafine. NND-502 exhibited strong in vitro antifungal
      activity against Trichophyton spp.; its MIC was 1 to 4 times lower than that of
      lanoconazole or terbinafine. In an in vivo study with a guinea pig model of tinea
      pedis, 7-day topical treatment with a 0.5% solution of NND-502 (dissolved in
      polyethylene glycol 400) was more effective than that with a 0.5% solution of
      either lanoconazole or terbinafine for eradicating fungi from the infected feet.
      When the duration of treatment was shortened to 3 days, a topical 1% solution of
      NND-502 achieved a complete mycological cure, while topical 1% solutions of
      lanoconazole and terbinafine did not.

PMID- 9559823
TI  - In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to
      two ketolides (HMR 3004 and HMR 3647), four macrolides (azithromycin,
      clarithromycin, erythromycin A, and roxithromycin), and two ansamycins (rifampin
      and rifapentine).
AB  - When tested by agar dilution on Mueller-Hinton agar supplemented with 5% horse
      blood, the ketolides HMR 3004 and HMR 3647 were slightly more active (MIC at
      which 90% of the isolates were inhibited [MIC90], 0.03 microg/ml) against
      Bordetella pertussis than azithromycin, clarithromycin, erythromycin A, and
      roxithromycin. Azithromycin (MIC90, 0.06 microg/ml) was the most active compound
      against B. parapertussis. Rifampin and rifapentine were considerably less active.

PMID- 9559825
TI  - Human cytomegalovirus mutant with sequence-dependent resistance to the
      phosphorothioate oligonucleotide fomivirsen (ISIS 2922).
AB  - A human cytomegalovirus mutant that was isolated for resistance (10-fold) to the
      antisense oligonucleotide fomivirsen (ISIS 2922) exhibited cross-resistance to a
      modified derivative of fomivirsen with an identical base sequence but little or
      no resistance to an oligonucleotide with an unrelated sequence. No changes in the
      mutant's DNA corresponding to the fomivirsen target sequence were found.

PMID- 9559826
TI  - Alginate lyase promotes diffusion of aminoglycosides through the extracellular
      polysaccharide of mucoid Pseudomonas aeruginosa.
AB  - We demonstrated that a 2% suspension of Pseudomonas aeruginosa alginate
      completely blocked the diffusion of gentamicin and tobramycin, but not that of
      carbenicillin, illustrating how alginate production can help protect P.
      aeruginosa growing within alginate microcolonies in patients with cystic fibrosis
      (CF) from the effects of aminoglycosides. This aminoglycoside diffusion barrier
      was degraded with a semipurified preparation of P. aeruginosa alginate lyase,
      suggesting that this enzyme deserves consideration as an adjunctive agent for CF
      patients colonized by mucoid strains of P. aeruginosa.

PMID- 9559827
TI  - Susceptibilities of clinical and laboratory isolates of Blastomyces dermatitidis
      to ketoconazole, itraconazole, and fluconazole.
AB  - Eighteen isolates of Blastomyces dermatitidis were evaluated for their in vitro
      susceptibilities to ketoconazole, itraconazole, and fluconazole. The MIC ranges
      were 0.1 to 0.4 microg/ml for ketoconazole, < or =0.018 to 0.07 microg/ml for
      itraconazole, and 2.5 to 4.0 microg/ml for fluconazole. The ranges for the
      minimal lethal concentrations were 0.2 to 0.8 microg/ml for ketoconazole, < or
      =0.018 to 0.07 microg/ml for itraconazole, and 10 to 40 microg/ml for
      fluconazole. Itraconazole was the most active agent against B. dermatitidis in
      vitro, while fluconazole was the least active. These results correlate with the
      clinical efficacies noted to date with doses of these agents used to treat
      blastomycosis.

PMID- 9559828
TI  - Efficacy of LY333328 against experimental methicillin-resistant Staphylococcus
      aureus endocarditis.
AB  - The in vivo efficacy of LY333328, a new glycopeptide antibiotic, was compared
      with that of vancomycin by using the rabbit model of left-sided methicillin
      resistant Staphylococcus aureus endocarditis. Animals received LY333328 or
      vancomycin (25 mg/kg of body weight every 24 or 8 h, respectively) for 4 days.
      These drugs were equally effective in clearing bacteremia and in reducing
      bacterial counts in vegetations and tissues. We conclude that in this model,
      LY333328 was microbiologically effective and may be a therapeutic alternative to
      vancomycin.

PMID- 9559829
TI  - In vitro activity of levofloxacin against a selected group of anaerobic bacteria
      isolated from skin and soft tissue infections.
AB  - The in vitro activity of levofloxacin was compared to the activities of
      ofloxacin, ciprofloxacin, ampicillin-sulbactam (2:1), cefoxitin, and
      metronidazole for a selected group of anaerobes (n = 175) isolated from skin and
      soft tissue infections by using the National Committee for Clinical Laboratory
      Standards-approved Wadsworth method. Ampicillin-sulbactam and cefoxitin inhibited
      99% of the strains of this select group, levofloxacin and ofloxacin inhibited 73
      and 50%, respectively, at 2 microg/ml, and ciprofloxacin inhibited 51% at 1
      microg/ml. The geometric mean MIC of levofloxacin was lower than those of
      ofloxacin and ciprofloxacin for every group except Veillonella.

PMID- 9559830
TI  - New antimicrobial agents approved by the U.S. Food and Drug Administration in
      1997 and new indications for previously approved agents.

PMID- 9559831
TI  - Emergence of erythromycin-resistant, clindamycin-susceptible Streptococcus
      pyogenes isolates in Madrid, Spain.

PMID- 9559832
TI  - Synergistic activity of trovafloxacin and ceftriaxone or vancomycin against
      Streptococcus pneumoniae with various penicillin susceptibilities.

PMID- 9559833
TI  - Pathophysiology of clinical varicoceles in infertile men.
AB  - In infertile men, clinical varicoceles most often occur bilaterally. In our
      experience with these patients, both testicles are smaller than normal. We find
      more than 25% to 35% immature and tapered sperm in in the ejaculum of these men,
      and the motility of the sperm is usually low. We have found serotonin in the
      plasma of the varicoceles, and believe this biogenic amine is responsible for the
      poor sperm motility. We now agree that a subset of neuroendocrine cells in the
      prostate secrete serotonin. Bilateral varicocele surgery can improve the
      patient's fertility potential, and we advocate surgical treatment.

PMID- 9559834
TI  - Preliminary report of a modified continent appendix stoma in a sigmoid urinary
      reservoir pouch.
AB  - BACKGROUND: The application of an appendix stoma in a Mainz urinary reservoir
      pouch is an established procedure and assures good continence. We modified this
      method for use with a sigmoid pouch. METHODS: In each of 3 men with bladder
      carcinoma, an appendix with a blood supply was prepared and anastomosed to the
      detubularized sigmoid pouch with a 3-cm submucosal tunnel. RESULTS: In all 3
      patients, this procedure was performed successfully, and the pouch was completely
      continent. Self-catheterization could be performed without difficulty by 2
      patients, and with slight resistance in the remaining patient. The patients are
      satisfied with their quality of life. CONCLUSIONS: We conclude, based on our
      findings and these preliminary observations, that this procedure is a potentially
      good alternative for the placement of continent stoma in continent urinary
      reservoir surgery.

PMID- 9559835
TI  - Evaluation of the prognostic significance of microvessel count and tumor size in
      renal cell carcinoma.
AB  - BACKGROUND: We analyzed the significance of tumor microvessel count and tumor
      size as prognostic factors for renal cell carcinoma (RCC). METHODS: T criteria
      (local invasion), M criteria (distant metastasis), macrovenous invasion,
      histological grade, cell type, tumor size, and tumor microvessel count were
      investigated as prognostic factors in 62 patients with RCC. Microvessel density
      was evaluated by immunohistochemical staining of the endothelial cells. RESULTS:
      No significant correlation was found between tumor size and the other prognostic
      factors. Analysis of the survival rate based on tumor size revealed that patients
      with a small tumor tended to show a good prognosis, but no significant difference
      was found in the prognosis between medium-sized and large-sized tumor groups.
      Analysis of all patients revealed that M criteria, macrovenous invasion, cell
      type and microvessel count were significant factors and that in 37 patients with
      low-stage tumors, the only significant prognostic factor was microvessel count
      (P=0.003). CONCLUSION: Tumor size cannot be readily justified as a determinant of
      prognosis in patients with medium- or large-sized tumors. In patients with low
      stage tumors, microvessel count served as the only significant determinant for
      prognosis. When the patients were considered as a whole, microvessel count, M
      criteria, macrovenous invasion and histological grade were significant prognostic
      factors.

PMID- 9559836
TI  - Clinical study of renal cell carcinoma with brain metastasis.
AB  - BACKGROUND: The clinical outcome of patients with renal cell carcinoma with brain
      metastasis was analyzed. METHODS: Nine patients (median age, 60 years) with
      primary renal cell carcinoma and distant metastasis, including brain metastasis,
      were treated. The median time to the development of brain metastasis was 15
      months after the initial visit. Patients with poor performance status or
      progressive disease were treated with interferon or conservative therapy alone.
      Patients with good performance status and other well-controlled metastatic foci
      were treated either with radiotherapy, or by tumorectomy of brain metastasis, or
      both. The median follow-up was 26 months after the initial visit. RESULTS: The 1
      year, cause-specific survival rate was 17%. Of the 5 patients treated with alpha
      interferon alone, all died of disease after the treatments, without improvement
      of performance status, 1 to 4 months after the diagnosis of brain metastasis. Two
      of 4 patients who underwent radiotherapy were treated with a combination of gamma
      knife and tumorectomy of brain metastasis. They remained alive 10 and 22 months
      after diagnosis of brain metastasis. The 2 patients who underwent the combination
      treatment of gamma-knife and tumorectomy showed improvement of their performance
      status after these treatments for brain metastasis. CONCLUSION: Brain metastasis
      is an unfavorable prognostic factor in renal cell carcinoma. Although a larger
      number of patients would be necessary to demonstrate the definitive effects of
      gamma-knife treatment, our results suggest that the combination of gamma-knife
      and tumorectomy of brain metastases may be recommended for selected patients with
      good performance status and other well-controlled metastatic foci.

PMID- 9559837
TI  - Combined treatment of staghorn calculi by fiberoptic transurethral
      nephrolithotripsy and extracorporeal shock wave lithotripsy.
AB  - BACKGROUND: Although various strategies have been proposed, the treatment of
      staghorn calculi is still controversial. We report on the treatment of 27
      staghorn calculi using fiberoptic transurethral nephrolithotripsy (f-TUL)
      combined with extracorporeal shock wave lithotripsy (ESWL). METHODS: Stones were
      initially disintegrated by f-TUL as an inpatient procedure. For stone
      fragmentation, we originally used an electrohydraulic lithotriptor (EHL) but
      changed to a pulsed-dye laser in 1993. After the stones were disintegrated as
      much as possible, a double-J ureteral stent was inserted and the patient was
      discharged. ESWL for the residual fragments was begun on an outpatient basis at 1
      or 2 weeks after f-TUL and repeated until the residual fragments were smaller
      than 4 mm. RESULTS: Since 1989, 27 staghorn calculi in 26 patients have been
      treated. Among them, 21 were successfully fragmented using this combined
      treatment regimen. From 3 to 26 ESWL sessions (mean, 8.4 sessions) were required
      to disintegrate the staghorn calculi. Auxiliary percutaneous endourological
      procedures were necessary in 2 cases due to ureteral obstruction. The other 4
      patients are still receiving ESWL for residual fragments. Urinary tract injury
      occurred in 2 patients early in this series when an EHL was used, but was managed
      without any surgical procedures. A fever greater than 38 degrees C developed in 9
      patients. CONCLUSION: Combining f-TUL with ESWL provides an alternative treatment
      option for staghorn calculi. The use of a small caliber fiberscope (2.6 mm in
      diameter) and a laser for fragmentation decreased the risk of complications.

PMID- 9559838
TI  - Smoking and obesity in relation to the etiology and disease progression of
      prostate cancer in Japan.
AB  - BACKGROUND: Various risk factors have been investigated concerning the etiology
      of prostate carcinoma, but many questions about the significance of the risk
      factors remain unanswered. To evaluate the relationship between smoking and
      obesity in prostate cancer, a case-control study was performed. METHODS: Between
      1986 and 1995, 329 patients with untreated prostate cancer and 188 patients with
      benign prostate hyperplasia (control patients) were evaluated according to their
      smoking habits and the degree of obesity. Also, the progression of prostate
      cancer in relationship to smoking and obesity was examined. RESULTS: Smoking and
      obesity were not risk factors for the development of prostate cancer (odds ratio,
      0.986, 0.836; 95% confidence interval, 0.69-1.41, 0.57-1.24, respectively). Nor
      were smoking or obesity a risk factor for survival in stage D2 patients, however,
      in stage B1-D1 patients, obese men had a tendency for disease progression.
      CONCLUSION: This study demonstrated that neither smoking nor obesity increase the
      risk of developing prostate cancer, or the risk of disease progression in
      prostate cancer patients. However, obese men have a tendency for progression of
      stage B1-D1 prostate cancer although further studies are necessary to confirm
      this finding.

PMID- 9559839
TI  - Familial prostate cancer in Japan.
AB  - BACKGROUND: Familial prostate cancer has been studied in Europe and the United
      States. This study was conducted to clarify the clinical features and incidence
      of the human leukocyte antigen (HLA) in familial prostate cancer in patients seen
      at hospitals in Japan. METHODS: The age at diagnosis, clinical stage, histologic
      differentiation, prognosis, cause of death and family history were compiled from
      43 patients from 20 families with familial prostate cancer (group F) and compared
      in patients with sporadic prostate cancer (group S). In addition, HLA class II
      gene typing was performed in 17 patients from 11 families with familial prostate
      cancer (group F') and their healthy family members (15 males and 25 females).
      RESULTS: The age at diagnosis was significantly lower in group F patients (P<
      0.001), but neither clinical stage nor prognosis differed between group F and
      group S, yet the incidence of moderately differentiated adenocarcinoma was
      significantly higher in group F (P< 0.01 ). There were no historical factors that
      were specific for group F patients. The frequency of HLA-DRB1 *0901 and *1201
      alleles was significantly higher in group F' patients than in group J (the
      frequency of alleles in 1216 Japanese people attending the 11th Japan HLA
      Workshop), but not between group F' and their healthy male family members.
      CONCLUSION: There were no significant differences in clinical parameters between
      group F and group S, except that the age at diagnosis was lower in group F
      patients, and that the frequency of several HLA class 11 alleles was
      significantly higher in patients with prostate cancer. In men with a family
      history of prostate cancer, examinations for early detection of prostate cancer
      should begin at a young age.

PMID- 9559840
TI  - Public awareness and knowledge of prostate cancer in Japan: results of a survey
      at short-stay examination facilities.
AB  - BACKGROUND: This study was undertaken to determine public awareness and knowledge
      of prostate cancer, which has not been adequately studied in Japan. METHODS:
      Assessment was made of public awareness and perception of prostate cancer in
      Japan, based on health examination data for participants in a short-stay physical
      examination program ("human dry dock"). A multiple-choice, thirty-point
      questionnaire survey was conducted at 3 "human dry dock" medical facilities
      situated in urban areas. RESULTS: Many Japanese adults appeared to be
      inadequately aware of prostate cancer and of the means available for its early
      detection. One third of the participants were unfamiliar with this malignancy.
      Logistic regression analysis indicated smoking to be the only covariate
      associated with lack of knowledge of prostate cancer (P< 0.05). Seventy-one
      percent of the subjects had heard of digital rectal examination, but only 16% and
      8%, respectively, were familiar with the terms transrectal ultrasonography and
      PSA testing. Japanese people may possibly be less informed about prostate cancer
      than African-American males. Both "human dry dock" facilities and subject gender
      were significantly associated with knowledge of digital rectal examination (P<
      0.05). Knowledge of transrectal ultrasonography was found to depend on
      participation in "human dry dock" programs and level of education (P< 0.05).
      Smoking, participation in "human dry dock" programs under employer direction, and
      health status were all identified as determinants for knowledge of PSA testing
      (P< 0.05). CONCLUSION: Educational programs should be established and put into
      effect to instill adequate awareness of prostate cancer in Japan. In a better
      informed society, more effort would be directed toward prevention and thus early
      stage prostate cancer would be detected more often.

PMID- 9559841
TI  - Holmium:YAG laser resection of the prostate versus visual laser ablation of the
      prostate and transurethral ultrasound-guided laser induced prostatectomy: a
      retrospective comparative study.
AB  - BACKGROUND: Transurethral resection of the prostate (TUR-P) is the gold standard
      for treating symptomatic benign prostatic hyperplasia (BPH) despite some
      perioperative morbidity. As a minimally-invasive alternative to TUR-P, a
      neodymium:YAG laser, and more recently a holmium:YAG laser, have been used in
      transurethral surgery for BPH. In order to assess the safety and efficacy of
      various BPH treatments, the outcome in patients treated with transurethral
      ultrasound-guided laser induced prostatectomy (TULIP), visual laser ablation of
      the prostate (VLAP) and holmium:YAG laser resection of the prostate (HoLRP) were
      retrospectively compared. METHODS: From May 1995 to August 1996, 60 patients with
      symptomatic BPH underwent TULIP (n=20), VLAP (n=20), and HoLRP (n=20). All
      patients were evaluated preoperatively and at 1 and 3 months postoperatively by
      the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score
      (QOL), maximum flow rate (MFR), prostate volume, and residual urine volume.
      RESULTS: The preoperative mean IPSS was 18.5, 19.3, and 19.6 and the mean MFR was
      6.3, 6.9, and 6.1 mL/sec in the TULIP, VLAP, and HoLRP groups, respectively. At 1
      month after surgery, the mean IPSS was 10.2, 9.5, and 4.7 and the mean MFR was
      9.6, 13.4, and 18.7 mL/sec while at 3 months the mean IPSS was 6.2, 6.1, and 3.6
      and the mean MFR was 14.1, 16.0, and 21.5 mL/sec in patients treated with TULIP,
      VLAP, and HoLRP, respectively. No serious complication occurred in any patient.
      CONCLUSION: Although HoLRP requires expertise, it appears to be a promising
      treatment modality for BPH.

PMID- 9559842
TI  - Transrectal microwave hyperthermia for patients with benign prostatic
      hyperplasia.
AB  - BACKGROUND: A randomized study evaluated the efficacy of treatment with
      transrectal microwave hyperthermia (TMH) treatment in patients with benign
      prostatic hyperplasia (BPH). METHODS: Eighty BPH patients received TMH therapy
      and 20 patients were given a sham treatment. TMH was achieved using a
      prostathermer which includes a microwave transrectal heat generator, a cooling
      system and a transurethral sensor probe. Patients that received TMH had 5 to 6
      sessions of 1 hour each where the prostate was heated to 42 degrees C to 43.5
      degrees C. The sham treatment consisted of a single session where the temperature
      was maintained at 37 degrees C. All patients were evaluated at 3 and 12 months
      after treatment. RESULTS: There was an improvement of subjective obstructive
      symptoms in 54 patients (75%) after TMH. An evaluation of urodynamic parameters
      revealed an increase in the maximum flow rate and a decrease of the detrusor
      opening pressure as well as the detrusor pressure at maximum flow in patients
      treated with TMH. A significant improvement in the amount of residual urine was
      seen in all TMH-treated patients (P < 0.0001). CONCLUSION: Although TMH cannot be
      considered a superior alternative to open surgical or transurethral excision of
      the prostate, it is a valid option for patients who have indwelling urethral
      catheters and for those at high surgical risk.

PMID- 9559843
TI  - Role of the transition zone for elevating serum prostate-specific antigen in
      benign prostatic hyperplasia.
AB  - BACKGROUND: Patients with benign prostatic hyperplasia (BPH) have a wide range of
      concentrations of PSA. However, it is not known what factors influence the
      concentration of serum PSA other than the prostate volume. BPH is composed of an
      enlarged transition zone (TZ) and other zones (nonTZ). The TZ is thought to play
      a more important role than the nonTZ in determining the concentration of serum
      PSA in BPH patients. METHODS: We investigated the individual glandular zone
      volume, the amount of PSA produced by each zone and the PSA density in each zone
      in 23 patients with histologically-confirmed BPH. The PSA density in the TZ was
      calculated by dividing the difference between the serum PSA before and after
      surgical resection by the specimen weight. We examined the influence of these
      parameters on the concentration of serum PSA in BPH patients. RESULTS: The serum
      PSA concentration correlated with the amount of PSA produced by the TZ (r=0.90,
      P< 0.0 1), but not the nonTZ (r=0.25, P=0.29). The concentration of serum PSA
      also showed a significant correlation with the TZ volume (r=0.67, P< 0.01) and
      the PSA density in the TZ (r=0.51, P< 0.05), but not with the PSA density in the
      nonTZ (r=-0.06, P=0.81). Also, age was inversely correlated with the PSA density
      in the TZ (r=-0.69, P< 0.01). CONCLUSION: The hypertrophic prostate cell volume
      (TZ volume) and activity (PSA density in the TZ) significantly correlated with
      the concentration of serum PSA in BPH patients, and the TZ cell activity
      decreased inversely with age in these BPH patients.

PMID- 9559844
TI  - Results of closure of urethrocutaneous fistulas after hypospadias repair.
AB  - BACKGROUND: Urethrocutaneous fistulas are one of the major causes of morbidity
      after hypospadias repair. METHODS: During the last 2.5 years, 26 patients
      underwent repair of 41 urethrocutaneous fistulas. These fistulas were repaired by
      a 3-layered closure method, by using meticulous surgical techniques aided by
      optical magnification. In large fistulas, a dermal subcutaneous flap was created
      and brought over the surgically repaired urethral fistula. RESULTS: Twenty-four
      of the 26 patients with urethrocutaneous fistulas after hypospadias repair had
      fistula closure, with a 92% success rate. CONCLUSION: A high success rate was
      obtained with a multilayered closure using meticulous techniques to repair
      urethrocutaneous fistulas.

PMID- 9559845
TI  - Nonfunctioning adrenal cortical cancer and analysis of the steroidogenic activity
      of the tumor: a case report.
AB  - An adrenocortical cancer was detected by a CT scan in a 37-year-old woman, which
      did not have an excessive secretion of steroids or catecholamines. The tumor was
      enhanced inhomogeneously by the bolus injection of contrast medium, and magnetic
      resonance imaging (MRI) showed that the tumor was hypointense compared to the
      liver on a T1-weighted image and was diffusely hyperintense on a T2-weighted
      image. Histologically, the tumor consisted predominantly of compact cells with
      marked cellular and nuclear pleomorphism, but no capsular or vascular invasion
      were observed. An analysis of the steroidogenic activity of the tumor revealed
      that the activity of mitochondrial P450c11beta was extremely reduced in the
      tumor.

PMID- 9559846
TI  - Right paranephric abscess as a rare late complication of laparoscopic
      cholecystectomy.
AB  - A laparoscopic cholecystectomy on a 63-year-old woman was uneventful. Twenty-one
      months after the operation she complained of dull right flank pain, loss of
      appetite, weight loss, and cough. CT of the abdomen showed an 8.5 cm mass
      adjacent to the posterior aspect of the upper pole of the right kidney. CT also
      demonstrated a small calcification (5 mm diameter) posterior to the upper pole of
      the right kidney. The patient underwent exploratory laparotomy 2 months after the
      presentation with flank pain. Examination of the mass showed a thick abscess wall
      and 250 mL of pus. The patient's symptoms improved after the abscess was drained.

PMID- 9559847
TI  - Renal cell carcinoma of extraordinarily large size: a case report.
AB  - One of our patients was a 66-year-old woman with a T2 renal cell carcinoma
      weighing 3900 g. Two years after radical nephrectomy the woman was alive and
      well. A survey of Japanese medical literature revealed that patients with renal
      cell carcinomas weighing more than 2000 g have an unexpectedly favorable
      prognosis with a 5-year survival rate of 76.9%.

PMID- 9559848
TI  - Successful treatment with polymyxin B immobilized fiber of septic shock
      complicated by renal stone.
AB  - We describe a patient with septic shock that was spontaneously complicated by
      calyceal diverticular calculus. The patient recovered from shock within a few
      days with treatment by extracorporeal elimination of endotoxin using a blood
      purification cartridge consisting of polymyxin B immobilized fiber. Standard open
      nephrolithotomy was performed, and the patient was discharged from the hospital 2
      months after admission.

PMID- 9559849
TI  - Laparoscopic nephrectomy in children: two case reports.
AB  - We successfully performed a laparoscopic nephrectomy on 2 young girls in March
      1994 and August 1994. The first patient was a 9-year-old girl with a hypoplastic
      kidney associated with an ectopic ureterocele, and the other was a 3-year-old
      girl with a nonfunctioning hydronephrotic kidney caused by stricture of the
      pyeloureteral junction. The operating times were 153 and 183 minutes,
      respectively. No complications occurred intraoperatively or postoperatively in
      either patient. The 9-year-old girl resumed normal daily activities by
      postoperative day 2, and the 3-year-old girl by postoperative day 3. Both girls
      were discharged on day 4.

PMID- 9559850
TI  - Nephrogenic adenoma in a patient with transitional cell carcinoma of the bladder
      receiving intravesical bacillus Calmette-Guerin.
AB  - A 76-year-old-man was admitted to our hospital for a recurrent bladder tumor. He
      had received intravesical bacillus Calmette-Guerin (BCG) treatment for a
      transitional cell carcinoma of the bladder. A follow-up cystoscopy revealed a
      solitary papillary tumor in the left bladder wall. A transurethral cold cup
      biopsy revealed a nephrogenic adenoma without any evidence of malignant cells. We
      discuss the pathogenesis of nephrogenic adenoma and suggest that prolonged
      cystitis caused by intravesical BCG may play an etiological role.

PMID- 9559851
TI  - Detrusor areflexia in a patient with myasthenia gravis.
AB  - Myasthenia gravis (MG) is a common neuromuscular disorder, however, voiding
      dysfunction in conjunction with MG is rare. A review of the literature yielded
      only 7 prior reports of such a combination. Most of the reported cases involved
      incontinence in males which developed after a transurethral resection of the
      prostate. Only 3 cases described de novo voiding dysfunction. We report a fourth
      patient. In all 4 cases of de novo dysfunction, the voiding problem either
      heralded a new diagnosis of MG or an exacerbation of the disease process. It is
      hypothesized that autonomic dysfunction in patients with MG might indicate a
      unique subset with a worse prognosis.

PMID- 9559852
TI  - Congenital megalourethra: a case report.
AB  - We describe a case of a male infant with a scaphoid megalourethra. A physical
      examination showed a large, flabby phallus with bilateral undescended testes. The
      corpus spongiosum was absent with normal corpora cavernosa. Urethrography showed
      a crescent-shaped dilatation of the anterior urethra. Further examination
      revealed an association with concomitant urogenital anomalies, right renal
      hypoplasia-dysplasia, bilateral vesicoureteral reflux and the prune-belly
      syndrome. A urethroplasty with resection of the excess urethral tissue and
      reconstruction of the urethra was performed. There was a satisfactory surgical
      result and the patient now voids without difficulty.

PMID- 9559853
TI  - Minireview: on the structure and gating mechanism of the mitochondrial channel,
      VDAC.
AB  - There is considerable evidence that the voltage-gated mitochondrial channel VDAC
      forms a beta-barrel pore. Inferences about the number and tilt of beta-strands
      can be drawn from comparisons with bacterial beta-barrel pores whose structures
      have been determined by x-ray crystallography. A structural model for VDAC is
      proposed (based on sequence analysis and electron crystallography) in which the
      open state is like that of bacterial porins with several important differences.
      Because VDAC does not occur as close-packed trimers, there are probably fewer
      interpore contacts than in the bacterial porins. VDAC also appears to lack a
      large, fixed intraluminal segment and may not have as extensive a region of
      uniformly 35 degrees -tilted beta-strands as do the bacterial porins. These
      structural differences would be expected to render VDAC's beta-barrel less stable
      than its bacterial counterparts, making major conformational changes like those
      associated with gating more energetically feasible. A possible gating mechanism
      is suggested in which movement of the N-terminal alpha-helix out of the lumen
      wall triggers larger-scale structural changes.

PMID- 9559854
TI  - The intriguing evolution of the "b" and "G" subunits in F-type and V-type
      ATPases: isolation of the vma-10 gene from Neurospora crassa.
AB  - We have characterized the vma-10 gene which encodes the G subunit of the vacuolar
      ATPase in Neurospora crassa. The gene is somewhat unusual in filamentous fungi
      because it contains five introns, comprising 71% of the region between the
      translation start and stop codons. The 5' untranslated region of the gene
      contains several elements that have been identified in other genes that encode
      subunits of the vacuolar ATPase in N. crassa. A comparison of G subunits from N.
      crassa, S. cerevisiae, and animal cells showed that the N-terminal half of the
      polypeptide shows the highest degree of sequence conservation. Most striking is
      the observation that this region could form an alpha helix in which all of the
      conserved residues are clustered on one face. Subunit G appears to be homologous
      to the b subunit found in F-type ATPases. The major difference between the b and
      G subunits is the lack of a membrane-spanning region in the G subunit. We have
      also identified homologous subunits in the operons which encode V-type ATPases in
      a eubacterium, Enterrococcus hirae, and an archaebacterium, Methanococcus
      jannaschii. As in eukaryotic vacuolar ATPases the G subunit homologs lack a
      membrane-spanning region. Although the b and G subunits appear to be derived from
      a common ancestor, significant changes have evolved. In F-type and V-type ATPases
      these subunits can have zero, one, or two membrane-spanning regions and can also
      differ significantly in the number of copies per enzyme.

PMID- 9559855
TI  - Bacterial overexpression of putative yeast mitochondrial transport proteins.
AB  - Thirty-two genes have been identified within the genome of the yeast
      Saccharomyces cerevisiae which putatively encode mitochondrial transport
      proteins. We have attempted to overexpress a subset of these genes, namely those
      which encode mitochondrial transporters of unknown function, and have succeeded
      in overexpressing 19 of these genes. The overexpressed proteins were then
      isolated and tested for five well-characterized reconstituted transport
      activities (i.e., the transport of citrate, dicarboxylates, pyruvate, camitine,
      and aspartate). Utilizing this approach, we have clearly identified the yeast
      mitochondrial dicarboxylate transport protein, as well as two additional lower
      magnitude transport functions (i.e., tricarboxylate and dicarboxylate transport
      activities). The implications of these results and the considerations relevant to
      this approach are discussed.

PMID- 9559856
TI  - Localized firefly luciferase probes ATP at the surface of mitochondria.
AB  - The concentration of ATP generated by yeast mitochondria and consumed by yeast
      hexokinase was monitored using native firefly luciferase in solution, or
      recombinant luciferase localized at the surface of mitochondria. In the absence
      of hexokinase, both probes perform similarly in detecting exogenous or
      mitochondrially-generated ATP. The steady-state concentrations of ATP can be
      reduced in a dose-dependent manner by hexokinase. With hexokinase added in large
      excess, the localized probe reports substantial ATP concentrations while none is
      detectable by soluble luciferase. Thus, ATP accumulates near the membrane where
      it appears, relatively to solution, and vice versa for ADP. The extent of
      nucleotide gradients is shown to be correlated with the specific activity of
      oxidative phosphorylation and with the viscosity of the medium, but independent
      of the concentration of the organelles. A simple model involving diffusional
      restrictions is presented to describe this behavior. The metabolic and
      evolutionary implications of cellular catalysis limitation by physical processes
      are discussed.

PMID- 9559857
TI  - Oscillating Ca2+-induced channel activity obtained in BLM with a mitochondrial
      membrane component.
AB  - Oscillations in ion fluxes and membrane potential may be observed in cells and in
      mitochondria as well. We obtained Ca2+-induced oscillations in channel activity
      in black-lipid membranes reconstituted with hydrophobic components extracted from
      mitochondria. Mitoplasts prepared from purified rat liver mitochondria were
      extracted with ethanol followed by Folch extraction and further partial
      purification by silicic acid chromatography. Channel activity was measured in
      lipid bilayers formed from bovine brain lipids and 10% cardiolipin with addition
      of the purified fractions. The conductance with 10 mM Ca2+ was 100 pS or its
      multiples. Ca2+ gradients of 4: 1 induced oscillating channel activity for
      several hours, with initial open states of 40 s and closed states of 56 s; the
      open times gradually decreasing to 8.6 s. No channel activity was seen without
      added fractions. The channel activity was associated with a Ca2+-binding lipid,
      nonpolar, low-molecular-weight fraction that in gel electrophoresis was not
      stained with Coomassie Blue and did not contain carbohydrate-staining material.
      1H-Nuclear magnetic resonance spectra of the substance showed the presence of
      aliphatic chains and carbonyls, but the detailed structure remains to be
      elucidated.

PMID- 9559858
TI  - On the protection by inorganic phosphate of calcium-induced membrane permeability
      transition.
AB  - The role of inorganic phosphate as inhibitor of mitochondrial membrane
      permeability transition was studied. It is shown that in mitochondria containing
      a high phosphate concentration, i.e., 68 nmo/mg, Ca2+ did not activate the pore
      opening. Conversely, at lower levels of matrix phosphate, i.e., 38 nmol/mg, Ca2+
      was able to induce subsequent pore opening. The inhibitory effect of phosphate
      was apparent in sucrose-based media, but it was not achieved in KCI media. The
      matrix free Ca2+ concentration and matrix pH were lowered by phosphate, but they
      were always higher in K+-media. In the absence of ADP, phosphate strengthened the
      inhibitory effect of cyclosporin A on carboxyatractyloside-induced Ca2+ efflux.
      Acetate was unable to replace phosphate in the induction of the aforementioned
      effects. It is concluded that phosphate preserves selective membrane permeability
      by diminishing the matrix free Ca2+ concentration.

PMID- 9559859
TI  - Response of isolated rat liver mitochondria to variation of external osmolarity
      in KCl medium: regulation of matrix volume and oxidative phosphorylation.
AB  - When isolated rat liver mitochondria are incubated in KCI medium, matrix volume,
      flux, and forces in both hypo- and hyperosmolarity are time-dependent. In
      hypoosmotic KCl medium, matrix volume is regulated via the K+/H+ exchanger. In
      hyperosmotic medium, the volume is regulated in such a manner that at steady
      state, which is reached within 4 min, it is maintained whatever the
      hyperosmolarity. This regulation is Pi- and deltamuH+-dependent, indicating Pi-K
      salt entry into the matrix. Under steady state, hyperosmolarity has no effect on
      isolated rat liver mitochondria energetic parameters such as respiratory rate,
      proton electrochemical potential difference, and oxidative phosphorylation yield.
      Hypoosmolarity decreases the NADH/NAD+ ratio, state 3 respiratory rate, and
      deltamuH+, while oxidative phosphorylation yield is not significantly modified.
      This indicates kinetic control upstream the respiratory chain. This study points
      out the key role of potassium on the regulation of matrix volume, flux, and
      forces. Indeed, while matrix volume is regulated in NaCl hyperosmotic medium,
      flux and force restoration in hyperosmotic medium occurs only in the presence of
      external potassium.

PMID- 9559861
TI  - Estimation of membrane potential deltapsi in reconstituted plasma membrane
      vesicles using a numerical model of oxonol VI distribution.
AB  - A model of membrane potential-dependent distribution of oxonol VI to estimate the
      electrical potential difference deltapsi across Schizosaccharomyces pombe plasma
      membrane vesicles (PMV) has been developed. deltapsi was generated by the H+
      ATPase reconstituted in the PMV. The model treatment was necessary since the
      usual calibration of the dye fluorescence changes by diffusion potentials (K+ +
      valinomycin) failed. The model allows for fitting of fluorescence changes at
      different vesicle and dye concentrations, yielding deltapsi in ATP-energized PMV
      of 80 mV. The described model treatment to estimate deltapsi may be applicable
      for other reconstituted membrane systems.

PMID- 9559860
TI  - Energetics of isolated hepatocyte swelling induced by sodium co-transported amino
      acids.
AB  - This study was designed to investigate the energetics of isolated rat hepatocyte
      swelling due to sodium-cotransported amino acid accumulation in a medium
      containing either glucose or octanoate as basal substrate. We show that the size
      of the increase in cytosolic volume is directly correlated with the total amino
      acid accumulation, which depends on the difference of electrical potential across
      the plasma membrane. Such a change in cell volume, with either glucose or
      octanoate, does not modify the mitochondrial volume. Addition of sodium
      cotransported amino acids for which the metabolism was avoided showed that the
      rise in cell volume, per se, did not change the respiratory rate, deltap, or
      phosphate potential in either mitochondrial or cytosolic compartments.
      Conversely, the large increase in oxidative phosphorylation flux was due to the
      metabolism of amino acids as a consequence of a rise in electron supply for the
      respiratory chain rather than an increase in cellular ATP demand, as indicated by
      the increase in cytosolic phosphate potential. Moreover, although we confirm that
      octanoate addition largely increases the respiratory rate by a process different
      from uncoupling, we observed that the same overall thermodynamic driving force
      through the respiratory chain and the same mitochondrial or cytosolic phosphate
      potential were maintained for much higher oxygen consumption when octanoate was
      present. We propose that these octanoate effects are due to a decrease in the
      actual protons/2 electrons stoichiometry as a consequence of a shift in electron
      supply toward a two-coupling site instead of a three-coupling site. The change in
      the FADH2/NADH formation flux ratio in either fatty acid or carbohydrate
      oxidation explains such results.

PMID- 9559862
TI  - Direct measurement of nitrite transport across erythrocyte membrane vesicles
      using the fluorescent probe, 6-methoxy-N-(3-sulfopropyl) quinolinium.
AB  - Nitrite was shown to quench the fluorescence of 6-methoxy-N-(3-sulfopropyl)
      quinolinium (SPQ) almost twofold more than chloride. SPQ loaded inside vesicles
      prepared from asolectin and isolated erythrocyte ghosts allowed for the direct
      measurement of nitrite movement across these membranes. Movement of nitrite
      across asolectin occurred by diffusion as HNO2 in a pH-dependent manner. By
      contrast, erythrocyte ghosts had very low diffusion rates for nitrous acid.
      Erythrocyte ghosts preloaded with 50 mM nitrite to quench SPQ fluorescence were
      utilized to study heteroexchange with externally added anions. SPQ fluorescence
      increases (becomes unquenched) with added bicarbonate and nitrate, indicating
      that nitrite is moving out of the preloaded vesicles. The pH optimum for this
      exchange was approximately 7.6 and exchange was inhibited by N-ethylmaleimide
      (NEM) and dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). These
      data indicate that nitrite moves across erythrocyte plasma membranes as NO2- by a
      heteroexchange mechanism with other monovalent anions.

PMID- 9559863
TI  - The critical role of Hepes in SIN-1 cytotoxicity, peroxynitrite versus hydrogen
      peroxide.
AB  - The cytotoxicity of the superoxide anion radical- and nitric oxide-releasing
      compound SIN-1 to L929 cells was studied in Krebs-Henseleit buffer. pH 7.4, in
      the presence and absence of Hepes. SIN-1 cytotoxicity was significantly higher in
      the presence of Hepes than in the absence of Hepes. The available amount of
      peroxynitrite formed from SIN-1, however, was significantly decreased by Hepes as
      indicated by decreased oxidation of dihydrorhodamine 123. On the other hand,
      Hepes largely increased the formation of H2O2 from SIN-1. Catalase protected the
      L929 cells from SIN-1 cytotoxicity in the buffer with Hepes. In the buffer
      without Hepes catalase did not have any protective effect. In contrast, tyrosine
      and tryptophan provided significant protection against SIN-1 cytotoxicity
      independent of the presence of Hepes. These results demonstrate that the
      immediate toxic agent formed from SIN-1 decisively depends on the presence of
      Hepes. In its absence cytotoxicity is most likely mediated by peroxynitrite while
      in the presence of Hepes, cytotoxicity is conveyed by co-operative action of
      hydrogen peroxide and reactive nitrogen species.

PMID- 9559864
TI  - Antioxidant activity of lazaroid (U-75412E) and its protective effects against
      crystalline silica-induced cytotoxicity.
AB  - Lazaroids (21-amino steroids) are believed to be powerful scavengers of reactive
      oxygen species (ROS) and inhibitors of lipid peroxidation. Crystalline silica, a
      potent cytotoxic agent, causes pulmonary fibrosis in experimental animals and
      humans. ROS have been previously shown to be involved in crystalline silica
      induced pulmonary injury and inflammation. In the present study, the reaction
      rate of lazaroid (U-75412E) with hydroxyl radical (.OH) generated by Fenton
      reaction (Fe(II) + H2O2 --> Fe(III) + OH- + .OH) was investigated using ESR spin
      trapping competition reactions. The reaction rate constant was found to be 1.0 x
      10(10) M(-1)s(-1), which was comparable with those of other efficient .OH radical
      scavengers. As indicators of crystalline silica-induced cytotoxicity and its
      protection by this antioxidant lazaroid (U-75412E) we measured lactate
      dehydrogenase, N-acetyl-beta-glucosaminidase, superoxide dismutase, glutathione
      peroxidase, and hydrogen peroxide released from rat alveolar macrophages. Lipid
      peroxidation, a prominent manifestation of .OH radical-induced cell injury, was
      also measured to evaluate the protective value of lazaroid. Alveolar macrophages
      treated with lazaroid (U-75412E) before crystalline silica exposure were
      protected against cell injury and lipid peroxidation as demonstrated by those
      indicators. Lazaroid (U-75412E) scavenges .OH radicals generated by crystalline
      silica-mediated reaction from H2O2 and inhibits lipid peroxidation in macrophages
      induced by these particles.

PMID- 9559865
TI  - One- and two-electron oxidations of luminol by peroxidase systems.
AB  - The kinetics of luminol oxidation catalyzed by horseradish peroxidase (HRP),
      Arthromyces ramosus peroxidase (ARP) and lactoperoxidase (LPO) at pH 7.0 was
      investigated. One-electron oxidation of luminol by peroxidase systems was
      inferred from the detection of luminol radicals, luminol-mediated formation of
      ascorbate radicals, and the trapping of luminol-mediated GSH radicals. The
      catalytic intermediate of peroxidases in the steady state was Compound II and the
      rate constants of HRP, ARP, and LPO Compound II with luminol were 3.6 x 10(4),
      1.1 x 10(7), and 2.5 x 10(4) M(-1)s(-1), respectively. The intensity of luminol
      chemiluminescence (CL) generated by the peroxidases depended on the rate
      constants of the rate-determining step. The luminol CL catalyzed by peroxidases
      increased with an increase in the concentration of H2O2 and was inhibited in the
      presence of catalase. Neither oxygen consumption during the reaction under
      aerobic conditions nor a change of light intensity under anaerobic conditions was
      observed. The light emission and oxidation of luminol catalyzed by LPO was
      increased by trace amounts of iodide. LPO catalyzes two-electron oxidations of
      iodide to form iodinating intermediate (Nakamura, M.; et al. J. Biol. Chem.
      260:13546-13552, 1985), which subsequently oxidizes luminol. The results lead us
      to conclude that CL of luminol was initiated by peroxidase systems irrespective
      of one- or two-electron oxidations of luminol.

PMID- 9559866
TI  - Enhanced gamma-glutamyl transpeptidase expression and selective loss of CuZn
      superoxide dismutase in hepatic iron overload.
AB  - Liver injury caused by iron overload is presumed to involve lipid peroxidation
      and the formation of products such as 4-hydroxynonenal (4HNE), which has been
      implicated in hepatic fibrogenesis. Cellular antioxidants that modulate the
      formation and detoxification of compounds such as 4HNE may represent important
      protective mechanisms involved in the response to iron overload. This study
      examines the relationship between 4HNE, collagen content, and antioxidant
      defenses in the livers of rats fed carbonyl iron for 10 weeks. Iron-loading
      resulted in significant increases in iron (8.8-fold), 4HNE (1.7-fold), and
      hydroxyproline (1.5-fold). Total glutathione content was unchanged by iron, but
      gamma-glutamyl transpeptidase activity (GGT) increased sixfold and CuZn
      superoxide dismutase (CuZnSOD) activity decreased >9%. GGT colocalized with iron
      deposition and was associated with increased GGT mRNA. Decreased CuZnSOD activity
      was paralleled by a reduction in CuZnSOD protein on Western blot and
      immunohistochemistry, but no decrease in CuZnSOD mRNA. Glutathione S-transferase
      (GST) and Mn superoxide dismutase (MnSOD) activities were also significantly
      increased by iron loading. These results demonstrate that iron overload
      significantly alters the expression of antioxidant enzymes associated with
      glutathione (GGT and GST) and superoxide metabolism (CuZnSOD and MnSOD).
      Furthermore, the localized induction of GGT may enhance detoxification of lipid
      peroxidation-derived aldehydes via glutathione-dependent pathways in iron-loaded
      hepatocytes. These alterations in antioxidant defenses may represent an adaptive
      response, limiting accumulation 4HNE, and thus, stimulation of collagen
      synthesis, accounting for the mild fibrogenic response seen in this model of iron
      overload.

PMID- 9559867
TI  - Different mechanisms of thioredoxin in its reduced and oxidized forms in defense
      against hydrogen peroxide in Escherichia coli.
AB  - The present experiments were done to elucidate the roles of thioredoxin and
      thioredoxin reductase system in defense against hydrogen peroxide (H2O2) in
      Escherichia coli. The thioredoxin-deficient mutant (trxA) was more sensitive to
      H2O2 than was the wild-type strain, when challenged in the stationary and
      exponentially growing phase. Thioredoxin reductase-deficient mutant (trxB) in the
      stationary phase also exhibited increased sensitivity, compared with the wild
      type strain. These results indicated that reduced form of thioredoxin is required
      for defense against H2O2, possibly by scavenging radicals generated in the cells.
      In contrast, the trxB mutant in the growing phase had higher survival after
      exposure to H2O2 than the wild-type strain. The acquirement of resistance related
      to increased capacity for removing H2O2 in the trxB mutant and was not observed
      in a catalase-negative background. Furthermore, enhanced expression of the katG
      :: lacZ gene occurred in the mutant. Therefore, it was concluded that oxidized
      form of thioredoxin confers H2O2 resistance on E. coli cells by increasing
      activity to remove H2O2, which was brought about by enhanced induction of the
      katG-coded catalase/hydroperoxidase I at the transcriptional level. In addition,
      this resistance to H2O2 correlated well with reduced amount of DNA damage caused
      by H2O2, determined by the induction level of the recA :: lacZ fusion gene after
      treatment with H2O2.

PMID- 9559868
TI  - Hydroxyl radical as a potential intracellular mediator of polymorphonuclear
      neutrophil apoptosis.
AB  - We investigated reactive oxygen species (ROS) involvement in polymorphonuclear
      neutrophilic leukocyte (neutrophil) apoptosis triggering. Neutrophils were
      incubated with xanthine oxidase (XO), which produces superoxide anion (O2.-) and
      hydrogen peroxide (H2O2) or glucose oxidase (GO), which produces only H2O2. Both
      XO and GO accelerated apoptosis when compared to spontaneously aged neutrophils.
      Catalase inhibited both spontaneous apoptosis and XO- or GO-accelerated
      apoptosis, but superoxide dismutase did not. Hydrogen peroxide can enter the
      cell, thus generating intracellular oxidation, which was observed by flow
      cytometry. Furthermore, the intracellular reduced glutathione content fell in the
      presence of XO or GO; however, apoptosis was not accelerated in the presence of
      buthionine sulfoximine (BSO), suggesting that the fall in glutathione in the
      presence of XO or GO is a consequence of oxidative stress but not a trigger of
      apoptosis. Hydrogen peroxide can react with iron to form hydroxyl radicals (HO.);
      we observed that two iron chelators, deferoxamine and hydroxybenzyl
      ethylenediamine (HBED), both inhibited spontaneous and accelerated apoptosis,
      suggesting that HO. may mediate neutrophil apoptosis.

PMID- 9559869
TI  - Demonstration of the production of oxygen-centered free radicals during
      electrolysis using E.S.R. spin-trapping techniques: effects on cardiac function
      in the isolated rat heart.
AB  - The present study was designed to identify the free radicals generated during the
      electrolysis of the solution used to perfuse isolated rat heart Langendorff
      preparations. The high reactivity and very short half-life of oxygen free
      radicals make their detection and identification difficult. A diamagnetic organic
      molecule (spin trap) can be used to react with a specific radical to produce a
      more stable secondary radical or "spin adduct" detected by electron spin
      resonance (ESR). Isovolumic left ventricular systolic pressure (LVSP) and left
      ventricular end diastolic pressure (LVEDP) were measured by a fluid-filled latex
      balloon inserted into the left ventricle. The coronary flow was measured by
      effluent collection. Electrolysis was performed with constant currents of 0.5, 1,
      1.5, 3, 5, 7.5, and 10 mA generated by a Grass stimulator and applied to the
      perfusion solution for 1 min. A group of experiments was done using a 1.5 mA
      current and a Krebs-Henseleit (K-H) solution containing free radical scavengers
      (superoxide dismutase (SOD): 100 IU/ml or mannitol: 50 mM). Heart function
      rapidly declined in hearts perfused with K-H buffer that had been electrolyzed
      for 1 min. The addition of mannitol (50 mM) to the perfusion solution had no
      effect on baseline cardiac function before electrolysis while SOD (100 IU/ml)
      increased the coronary flow. However, SOD was more effective than the mannitol in
      protecting the heart against decreased of cardiac function, 5 min after the end
      of electrolysis. Samples of the K-H medium subjected to electrolysis were
      collected in cuvettes containing a final concentration of 125 mM 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO) and analyzed by spectroscopy. The ESR spectrum consisted
      of a quartet signal (hyperfine couplings aN = aH = 14.9 G) originating from the
      hydroxyl adduct signal, DMPO-OH. The intensity of the DMPO-OH signal remained
      stable during the 60 s of electrolysis and the quantity of free radicals induced
      by electrolysis was directly proportional to the intensity of the current. The
      addition of mannitol and SOD to the perfusate scavenged the hydroxyl radicals
      present in the solution, suggesting that both hydroxyl and superoxide radicals
      were formed during electrolysis.

PMID- 9559870
TI  - Oxidative damage, plasma antioxidant capacity, and glucemic control in elderly
      NIDDM patients.
AB  - A study of oxidative damage was made in elderly noninsulin-dependent diabetes
      mellitus (NIDDM) patients. A statistically significant increase in glucose and
      fructosamine was found in fasting NIDDM patients, as well as an increase in the
      oxidation induced by tert-butyl hydroperoxide. The Total Reactive Antioxidant
      Potential (TRAP) of the plasma was much reduced (p < .02) and the uricemia was
      unchanged. The erythrocytes of diabetic patients show greater basal oxidation
      products (p < .05), and the susceptibility of the diabetic erythrocytes to
      oxidation injury was also shown to increase in the oxidation induced by t-BOOH (p
      < .05). Linear regression studies showed that TRAP was associated directly with
      uric acid (p < .05) and inversely with fructosamine and with glucose (p < .03 and
      p < .05 respectively) in patients with NIDDM, but not in the controls. The levels
      of fructosamine were found to be related to the basal damage of the red blood
      cells (direct correlation, p < .001). This study suggest an useful approach to
      diabetic oxidative stress for clinical settings.

PMID- 9559871
TI  - Role of antioxidant enzymes on ionizing radiation resistance.
AB  - Exposure of cells to ionizing radiation leads to formation of reactive oxygen
      species (ROS) that are associated with radiation-induced cytotoxicity. The
      antioxidant enzymes manganese superoxide dismutase (MnSOD), copper-zinc
      superoxide dismutase (CuZnSOD), and glutathione peroxidase (GPx), are key
      intracellular antioxidants in the metabolism of ROS. We investigated the
      potential role of the three antioxidant enzymes in radioresistance by analyzing
      cell morphology, cell viability, and cellular radioresistance in stably
      transfected CHO cell lines overexpressing MnSOD, CuZnSOD, and GPx, respectively.
      We found that overexpression of human MnSOD substantially protected cells from
      ionizing radiation injury. Relative to MnSOD, GPx could slightly reduce the
      radiation sensitivity while the radioresistance in CuZnSOD expressing cells did
      not change significantly. The results suggested that MnSOD may play a central
      role in protecting cells against reactive oxygen species injury during ionizing
      radiation exposure among MnSOD, CuZnSOD, and GPx.

PMID- 9559872
TI  - Inhibition of peroxynitrite dependent tyrosine nitration by hydroxycinnamates:
      nitration or electron donation?
AB  - Peroxynitrite is a cytotoxic species generated by the reaction between superoxide
      and nitric oxide. In this study the ability of hydroxycinnamate antioxidants to
      decrease peroxynitrite-mediated nitration of tyrosine was investigated. The
      results obtained show that all compounds were able to inhibit nitration of
      tyrosine. The potency of inhibitory activity was in the order; caffeic acid > or
      = chlorogenic acid > or = ferulic acid > p-coumaric acid > ocoumaric acid > m
      coumaric acid. Trolox, which was included in the study for comparative purposes,
      had an activity between that of ferulic acid and p-coumaric acid. The data
      obtained suggest that hydroxycinnamates can act by one of two possible
      mechanisms: preferential nitration for monophenolates and electron donation by
      catecholates.

PMID- 9559873
TI  - Copper can promote oxidation of LDL by markedly different mechanisms.
AB  - Oxidation of LDL (0.1 microM) in PBS with copper concentrations ranging from 0.03
      to 10 microM, equal to 0.3-100 Cu2+/LDL, was investigated by monitoring the
      formation of conjugated dienes at 234 nm. With all 8 LDL samples examined, the
      kinetics changed strongly at submicromolar Cu2+ concentrations. Based on time
      course of the formation of conjugated dienes, cholesteryl linoleate hydroxides
      and hydroperoxides as well as the antioxidant consumption, two oxidation types
      were distinguished. Type A oxidations, observed at relatively high Cu2+
      concentrations of 10-100 Cu2+/ LDL, represented the conventional kinetics of LDL
      oxidation with an inhibition period (= lag-time) followed by a propagation phase.
      In contrast, type C oxidations proceeded after a negligibly short lag time
      followed by a distinct propagation phase. The rate of this propagation increased
      rapidly to 0.5 mol diene/mol LDL and then slowed down in the presence of alpha
      ,gamma-tocopherols and carotenoids, which were consumed faster than tocopherols.
      The increase in diene absorption was due to the formation of both hydroxides and
      hydroperoxides suggesting a high initial decomposition of hydroperoxides. At
      submicromolar concentrations of about 0.1 to 0.5 microM, type C and type A
      oxidation can be combined resulting in 4 consecutive oxidation phases, i.e. 1st
      inhibition and 1st propagation (belonging to type C), followed by 2nd inhibition
      and 2nd propagation (belonging to type A). Increasing copper concentrations
      lowered the 1st propagation and shortened the 2nd inhibition periods until they
      melted into one apparent kinetic phase. Decreasing [Cu2+] increased the 1st
      propagation and 2nd inhibition but lowered the 2nd propagation phase until it
      completely disappeared. A threshold copper concentration, denoted as Cu(lim), can
      be calculated as a kinetic constant based on the Cu2+-dependence for the rate of
      2nd propagation. Below Cu(lim), LDL oxidation proceeds only via type C kinetics.
      The Cu2+-dependence of the oxidation kinetics suggests that LDL contains two
      different Cu2+ biding sites. Cu2+ at the low-affinity binding sites, with half
      saturation at 5-50 Cu2+/LDL, initiates and accelerates the 2nd propagation by
      decomposing lipid hydroperoxides. Cu2+ bound to the high-affinity binding sites,
      with half-saturation at 0.3-2.0 Cu2+/LDL, is responsible for the 1st propagation.
      Arguments in favor and against this propagation being due to tocopherol mediated
      peroxidation (TMP) are discussed. If the lag-time concept is extended to the
      conjugated diene curves seen for combined oxidation profiles, then a true
      inhibition phase does not apply to this time interval, but instead represents the
      time elapsed before the onset of the 2nd propagation phase.

PMID- 9559874
TI  - Induction of the mitochondrial permeability transition causes release of the
      apoptogenic factor cytochrome c.
AB  - It was recently reported that the mitochondrial protein cytochrome c is required
      for the induction of apoptosis, and that the overexpression of Bcl-2 caused
      increased retention of this apoptogenic factor by mitochondria. Several cellular
      toxins, including H2O2, tBOOH and Ca++, induce the Mitochondrial Permeability
      Transition (MPT); we tested the possibility that MPT is an intracellular sensor
      of toxicity that results in the release of cytochrome c. We observe that the
      release of cytochrome c from purified mitochondria is stimulated by the classical
      inducers of MPT, and is inhibited by the classical inhibitor of MPT, cyclosporin
      A (CsA). After induction of MPT, mitochondrial supernatants gained the activity
      to induce cleavage of caspase 3 (CPP32) in cytosolic extracts, and this gain of
      activity was inhibited by CsA pretreatment of mitochondria, and was cancelled by
      immunodepletion of cytochrome c from the supernatants. After induction of MPT,
      mitochondrial supernatants mixed with or without cytosolic extract gained the
      activity to ladder nuclei, and this gain of activity was inhibited by CsA
      pretreatment of mitochondria, and cancelled by immunodepletion of cytochrome c
      from the supernatants. These results demonstrate that the induction of MPT causes
      release of cytochrome c from mitochondria, which is required for the hallmarks of
      cytosolic and nuclear apoptosis, caspase 3 activation and nuclear laddering, and
      identify the MPT as a potential intracellular sensor of oxidants and other
      toxins, and as a target for the pharmacological inhibition of apoptosis.

PMID- 9559875
TI  - GRP78, HSP72/73, and cJun stress protein levels in lung epithelial cells exposed
      to asbestos, cadmium, or H2O2.
AB  - Occupational exposure to crocidolite asbestos is associated with the development
      of nonmalignant and malignant pulmonary disease. Considerable evidence indicates
      that the mechanisms of asbestos-induced toxicity involve the production of active
      oxygen species (AOS). Production of AOS in excess of cellular defenses creates an
      environment of oxidative stress and stimulates the expression of a number of
      different genes whose products may be involved in mediating responses from
      oxidant injury. To further investigate the mechanisms of asbestos-induced
      pathogenicity, we have examined by Western blot analyses the induction of the
      stress response proteins GRP78 and HSP72/73 in rat lung epithelial cells (RLE)
      exposed to crocidolite asbestos. In comparative studies, we also examined GRP78,
      HSP72/73, and cJun expression in RLE cells exposed to equitoxic concentrations of
      cadmium chloride (CdCl2) and hydrogen peroxide (H2O2). Our results demonstrate
      that asbestos and H2O2 do not alter GRP78 or HSP72/73 protein levels in RLE
      cells, but do increase levels of cJun protein. Increases by asbestos and H2O2
      were not accompanied by alterations in cellular glutathione levels in this cell
      type, but asbestos caused elevations in protein levels of manganese-containing
      superoxide dismutase (MnSOD), an indirect indicator of oxidant stress. In
      contrast, exposure of cells to CdCl2 led to no changes in MnSOD protein levels,
      but increases in GRP78, HSP72/73, and cJun proteins as well as significant
      increases in oxidized and reduced thiol pools. Results suggest that environmental
      agents causing oxidative injury to lung epithelium elicit different patterns of
      stress responses.

PMID- 9559876
TI  - Cutaneous tolerance to nitroxide free radicals in human skin.
AB  - No data are available on the irritant effect of nitroxide free radicals in human
      skin. Nitroxides are important biomedical skin probes used in Electron
      Paramagnetic Resonance spectroscopy and imaging. Our purpose was to study the
      skin irritation potential of different nitroxide free radical structures in skin
      of healthy human subjects. We investigated the following nitroxides: Tempo
      (2,2,6,6-tetramethyl-1-piperidinoxy), Doxo (2,2,5,5-tetramethyl-3-oxazolidinoxy),
      Proxo (2,2,5,5-tetramethyl- -dihydro-pyrrolinoxy), and Imidazo (2,2,3,4,5,5
      hexamethyl-imidazoline-1-yloxyl). Cutaneous irritation was determined in human
      skin following a single application and after repetitive applications in
      comparison to the standardized irritant sodium lauryl sulfate (SLS). The response
      was evaluated clinically as well as by a bioengineering method analyzing
      transepidermal water loss (TEWL) and skin hydration (capacitance). The nitroxides
      were classified clinically from nonirritant (Imidazo, Proxo), to slightly
      irritant (Doxo, 100 mM), or moderately irritant (Tempo 100 mM) after a single
      application. The TEWL values were significantly increased by Doxo and Tempo, but
      capacitance values were not changed significantly. In the cumulative irritation
      test Tempo was scored as a slight irritant (10 mM). TOLH (2,2,6,6-tetramethyl-1
      hydroxypiperidin), the hydroxylamine of Tempo, which is the major skin
      metabolite, did not cause skin irritation after a single or repetitive
      applications. This may indicate that a loss of cellular reducing equivalents may
      be involved in the inflammation process caused by Tempo. The order of nitroxide
      irritation potency (Tempo > Doxo >> Imidazo = Proxo) is inverse to the order of
      nitroxide biostability in human skin (Imidazo = Proxo >> Doxo > Tempo). In
      conclusion, nitroxide free radicals are classified as nonirritant to moderately
      irritant in human skin. Particularly, the pyrrolidine and imidazoline type
      nitroxides have a low potential to cause acute or subacute skin toxicity.

PMID- 9559877
TI  - Double (fluorescent and spin) sensors for detection of reactive oxygen species in
      the thylakoid membrane.
AB  - A series of dansylated sterically hindered amines designed to trapping reactive
      oxygen species, were synthesized. Compounds were tested in isolated thylakoid
      membranes subjected to photoinhibition by excess photosynthetically active
      radiation (400-700 nm). DanePy showed good selectivity for singlet oxygen and the
      formation of nitroxide was detected by appearance of ESR signal and quenching
      fluorescence.

PMID- 9559878
TI  - Determination of optimal conditions for synthesis of peroxynitrite by mixing
      acidified hydrogen peroxide with nitrite.
AB  - The measured parameters for the formation of peroxynitrous acid via the reaction
      of acidified hydrogen peroxide with nitrous acid and its self-decomposition
      corroborate with an earlier suggested mechanism in which H2NO2+ nitrosates H2O2.
      The activation energies for the formation and decay of peroxynitrous acid have
      been determined to be 15 and 19 kcal/mol, respectively. We found that
      perchlorate, nitrate, sulfate and phosphate ions have no effect on the formation
      and decay rates, whereas chloride ions enhance the rate of the formation of
      peroxynitrous acid at low peroxide concentrations, and have no effect at high
      peroxide concentrations. This suggests that at relatively low concentration of
      H2O2, Cl- competes with H2O2 for H2NO+ to yield NOCl, which may also nitrosate
      H2O2. Simulation of the experimentally observed parameters for the decay and
      formation rates suggests that it is not possible to obtain 100% yield of
      peroxynitrite under any condition. High yields of peroxynitrite were obtained at
      room temperature using an efficient double mixer where acidified peroxide was
      mixed with nitrite; after an appropriate delay, the reaction was quenched with
      strong alkali. An excess of more than 10% of H2O2 over nitrite, or vice versa, is
      sufficient to get ca. 85-90% of peroxynitrite, almost free from nitrite or H2O2,
      respectively. The results also suggest that conventional use of ice-cold
      solutions of the reactants and the alkali solutions is not required if an
      efficient mixer and appropriate quenching times are available.

PMID- 9559879
TI  - Involvement of hydrogen peroxide in topoisomerase inhibitor beta-lapachone
      induced apoptosis and differentiation in human leukemia cells.
AB  - Beta-Lapachone a novel topoisomerase inhibitor, has been found to induce
      apoptosis in various human cancer cells. In this study we report that a dramatic
      elevation of hydrogen peroxide (H2O2) in human leukemia HL-60 cells following 1
      microM beta-lapachone treatment and that this increase was effectively inhibited
      by treatment with antioxidant N-acetyl-L-cysteine (NAC), ascorbic acid, alpha
      tocopherol. NAC strongly prevented beta-lapachone-induced apoptotic
      characteristics such as DNA fragmentation and apoptotic morphology. However,
      treatment of HL-60 cells with another topoisomerase inhibitor camptothecin (CPT)
      did not induce H2O2 production as compared to untreated cells. NAC also failed to
      block CPT-induced apoptosis. Correlated with these findings, we found that cancer
      cell lines K562, MCF-7, and SW620, contained high level of intracellular
      glutathione (GSH), were not elevated in H2O2 and were resistant to apoptosis
      after treatment with beta-lapachone. In contrast, cancer cell lines such as, HL
      60, U937, and Molt-4 which have lower level of GSH, were readily increased of
      H2O2 and were sensitive to this drug. Furthermore, ectopic overexpression of Bcl
      2 in HL-60 cells also attenuated beta-lapachone-induced H2O2 and conferred
      resistance to beta-lapachone-induced cell death. Beta-Lapachone at the
      concentration as low as 0.25 microM effectively induced HL-60 cells to undergo
      monocytic differentiation, as evidenced by CD14 antigenicity and alpha-naphthyl
      acetate esterase activity. Again, the beta-lapachone-induced monocytic
      differentiation was suppressed by NAC. These results suggest that intracellular
      H2O2 generation plays a crucial role in beta-lapachone-induced cell death and
      differentiation.

PMID- 9559880
TI  - Intramolecular electron transfer in the dipeptide, histidyltyrosine: a pulse
      radiolysis study.
AB  - The technique of pulse radiolysis has been used to investigate the possibility of
      intramolecular charge transfer in the dipeptide histidyltyrosine, following one
      electron oxidation of one of its amino acid residues. The radical anion, Br2.-
      was found to react with the dipeptide at pH 6.0 with a bimolecular rate constant
      of 2.3+/-0.2 x 10(7) dm3 mol(-1)s(-1) suggesting that it reacts very selectively
      with the histidine moiety. Spectral observations at, or close to the end of this
      reaction show only the presence of a tyrosinyl free radical (TyrO.), however,
      indicating that fast (>10(6) s(-1) intramolecular charge transfer has taken place
      between histidine radicals (His+.) and tyrosine (TyrOH). This finding was
      supported by the direct observation of the rate of formation of TyrO. in
      experiments with the free amino acids, histidine and tyrosine, under conditions
      where Br2.- reacted selectively with histidine. The bimolecular rate constant for
      the reaction between His+. and TyrOH was found to be 2.4+/-0.5 x 10(6) dm3 mol(
      1)s(-1). Taken together, the results of the study indicate that His+. is a
      relatively strong oxidising agent where (E (His+./His) > 770 mV at pH 6.0.

PMID- 9559881
TI  - Does acute exercise affect the susceptibility of low density lipoprotein to
      oxidation?
AB  - This study describes the effect of an acute exercise bout on the susceptibility
      of isolated low density lipoprotein (LDL) to in vitro oxidation. LDL was isolated
      from 23 subjects (exercisers, n = 11; sedentary, n = 12) immediately before and
      after a single bout of exercise (30 min of treadmill work at 55% & 70% peak
      oxygen consumption (VO2 peak) for exercisers and sedentary, respectively). A
      statistically significant decrease in lag time for LDL oxidation was observed
      following exercise compared to baseline (96.1+/-23.5 min vs. 92.1+/-23.3 minutes;
      n = 23, p < or = .03) using a 5 microM copper system. There was a statistically
      significant increase in plasma myeloperoxidase (MPO) levels following exercise
      compared to baseline values ( 1.58+/-.91 ng/dl versus 2.08+/-1.2 ng/dl; n = 12, p
      < or = .03). These results suggest that the 30 min exercise bout at a moderate
      intensity and duration was a sufficient oxidative stress to increase the
      susceptibility of LDL to in vitro oxidation. Additionally, the exercise bout
      appeared to activate neutrophils, subsequently releasing MPO protein.

PMID- 9559882
TI  - Interaction of N-benzoyl-D-phenylalanine and related compounds with the
      sulphonylurea receptor of beta-cells.
AB  - 1. The structure activity relationships for the insulin secretagogues N-benzoyl-D
      phenylalanine (NBDP) and related compounds were examined at the sulphonylurea
      receptor level by use of cultured HIT-T15 and mouse pancreatic beta-cells. The
      affinities of these compounds for the sulphonylurea receptor were compared with
      their potencies for K(ATP)-channel inhibition. In addition, the effects of
      cytosolic nucleotides on K(ATP)-channel inhibition by NBDP were investigated. 2.
      NBDP displayed a dissociation constant for binding to the sulphonylurea receptor
      (K(D) value) of 11 microM and half-maximally effective concentrations of K(ATP)
      channel inhibition (EC50 values) between 2 and 4 microM (in the absence of
      cytosolic nucleotides or presence of 0.1 mM GDP or 1 mM ADP). 3. In the absence
      of cytosolic nucleotides or presence of GDP (0.1 mM) maximally effective
      concentrations of NBDP (0.1-1 mM) reduced K(ATP)-channel activity to 47% and 44%
      of control, respectively. In the presence of ADP (1 mM), K(ATP)-channel activity
      was completely suppressed by 0.1 mM NBDP. 4. The L-isomer of N-benzoyl
      phenylalanine displayed a 20 fold lower affinity and an 80 fold lower potency
      than the D-isomer. 5. Introduction of a p-nitro substituent in the D
      phenylalanine moiety of NBDP did not decrease lipophilicity but lowered affinity
      and potency by more than 30 fold. 6. Introduction of a p-amino substituent in the
      D-phenylalanine moiety of NBDP (N-benzoyl-p-amino-D-phenylalanine, NBADP) reduced
      lipophilicity and lowered affinity and potency by about 10 fold. This loss of
      affinity and potency was compensated for by formation of the phenylpropionic acid
      derivative of NBADP. A similar difference in affinity was observed for the
      sulphonylurea carbutamide and its phenylpropionic acid derivative. 7. Replacing
      the benzene ring in the D-phenylalanine moiety of NBDP by a cyclohexyl ring
      increased lipophilicity, and the K(D) and EC50 values were slightly lower than
      for NBDP. Exchange of both benzene rings in NBDP by cyclohexyl rings further
      increased lipophilicity without altering affinity and potency. 8. This study
      shows that N-acylphenylalanines interact with the sulphonylurea receptor of
      pancreatic beta-cells in a stereospecific manner. Their potency depends on
      lipophilic but not aromatic properties of their benzene rings. As observed for
      sulphonylureas, interaction of N-acylphenylalanines with the sulphonylurea
      receptor does not induce complete inhibition of K(ATP)-channel activity in the
      absence of inhibitory cytosolic nucleotides.

PMID- 9559883
TI  - Phosphodiesterase profile of human B lymphocytes from normal and atopic donors
      and the effects of PDE inhibition on B cell proliferation.
AB  - 1. CD19+ B lymphocytes were purified from the peripheral blood of normal and
      atopic subjects to analyse and compare the phosphodiesterase (PDE) activity
      profile, PDE mRNA expression and the importance of PDE activity for the
      regulation of B cell function. 2. The majority of cyclic AMP hydrolyzing activity
      of human B cells was cytosolic PDE4, followed by cytosolic PDE7-like activity;
      marginal PDE3 activity was found only in the particulate B cell fraction. PDE1,
      PDE2 and PDE5 activities were not detected. 3. By cDNA-PCR analysis mRNA of the
      PDE4 subtypes A, B (splice variant PDE4B2) and D were detected. In addition, a
      weak signal for PDE3A was found. 4. No differences in PDE activities or mRNA
      expression of PDE subtypes were found in B cells from either normal or atopic
      subjects. 5. Stimulation of B lymphocytes with the polyclonal stimulus
      lipopolysaccharide (LPS) induced a proliferative response in a time- and
      concentration-dependent manner, which was increased in the presence of
      interleukin-4 (IL-4). PDE4 inhibitors (rolipram, piclamilast) led to an increase
      in the cellular cyclic AMP concentration and to an augmentation of proliferation,
      whereas a PDE3 inhibitor (motapizone) was ineffective, which is in accordance
      with the PDE profile found. The proliferation enhancing effect of the PDE4
      inhibitors was partly mimicked by the cyclic AMP analogues dibutyryl (db) cyclic
      AMP and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'-cyclic
      monophosphorothioate, Sp-isomer (dcl-cBIMPS), respectively. However, at
      concentrations exceeding 100 microM db-cyclic AMP suppressed B lymphocyte
      proliferation, probably as a result of cytotoxicity. Prostaglandin E2 (PGE2, 1
      microM) and forskolin (10 microM) did not affect B cell proliferation, even when
      given in combination with rolipram. 6. Inhibition of protein kinase A (PKA) by
      differentially acting selective inhibitors (KT 5720, Rp-8-Br-cyclic AMPS)
      decreased the proliferative response of control cells and reversed the
      proliferation enhancing effects of rolipram. 7. Importantly, PDE4 activity in
      LPS/IL-4-activated B lymphocytes decreased by about 50% compared to unstimulated
      control values. 8. We conclude that an increase in cyclic AMP, mediated by down
      regulation of PDE4 activity, is involved in the stimulation of B cell
      proliferation in response to LPS/IL-4. B cell proliferation in response to a
      mitogenic stimulus can be further enhanced by pharmacological elevation of cyclic
      AMP.

PMID- 9559884
TI  - S-nitrosothiols and the nitrergic neurotransmitter in the rat gastric fundus:
      effect of antioxidants and metal chelation.
AB  - 1. The effects of the antioxidants ascorbic acid and alpha-tocopherol and of the
      metal chelator ethylenediaminetetraacetic acid (EDTA) were studied on relaxations
      in response to S-nitrosothiols, authentic nitric oxide (NO) and nitrergic non
      adrenergic non-cholinergic stimulation of the rat gastric fundus. 2. The S
      nitrosothiols S-nitrosocysteine (1-100 nM), S-nitrosoglutathione (0.01-3 microM)
      and S-nitroso-N-acetylpenicillamine (0.01-3 microM) induced concentration
      dependent relaxations of the rat gastric fundus muscle strips, which were
      precontracted with prostaglandin F2alpha. The relaxations to all S-nitrosothiols
      were concentration-dependently enhanced by the antioxidants ascorbic acid (0.1-3
      microM) and alpha-tocopherol (3-30 microM) and inhibited by the metal chelator
      EDTA (26 microM). 3. Ascorbic acid and alpha-tocopherol alone did not induce a
      relaxation of the precontracted rat gastric fundus muscle strip. However, when
      ascorbic acid (1 microM) or alpha-tocopherol (1 microM) were injected in the
      organ bath 1 minute after S-nitrosoglutathione (0.1 microM) or after S-nitroso-N
      acetylpenicillamine (0.1 microM), they induced an immediate, sharp and transient
      relaxation. This relaxation was inhibited by the superoxide generator pyrogallol
      (2 microM). Such a relaxation to ascorbic acid or alpha-tocopherol was not
      observed in the presence of S-nitrosocysteine (10 nM). 4. Electrical field
      stimulation (0.5-4 Hz) of the precontracted rat gastric fundus strips induced
      frequency-dependent nitrergic relaxations which were mimicked by authentic NO (3
      300 nM) and by acidified sodium nitrite NaNO2 (0.3-10 microM). Ascorbic acid
      (0.33-3 microM), alpha-tocopherol (3-30 microM) or EDTA (26 microM) did not
      affect the relaxations to nitrergic stimulation, NO or NaNO2. 5. In summary,
      relaxations to S-nitrosothiols in the rat gastric fundus are enhanced by the
      antioxidants ascorbic acid and alpha-tocopherol and inhibited by the metal
      chelator EDTA. However, relaxations to nitrergic stimulation of the rat gastric
      fundus or those to authentic NO were not affected by the antioxidants or by the
      metal chelator. These results indicate that antioxidants and metal chelators have
      a different effect on the biological activity of S-nitrosothiols and on that of
      the nitrergic neurotransmitter. Therefore, our results suggest that S
      nitrosothiols do not act as intermediate compounds in nitrergic neurotransmission
      in the rat gastric fundus.

PMID- 9559885
TI  - Functional and biochemical evidence for diazepam as a cyclic nucleotide
      phosphodiesterase type 4 inhibitor.
AB  - 1. The responses of the electrically-driven right ventricle strip of the guinea
      pig heart to diazepam were recorded in the absence and in the presence of
      different selective cyclic nucleotide phosphodiesterase (PDE) inhibitors. 2.
      Diazepam, at concentrations ranging from 1 microM to 100 microM, was devoid of
      effect on the contractile force in this preparation. 3. Conversely, diazepam (5
      microM-100 microM) produced a consistent positive inotropic response in the
      presence of a concentration (1 microM), that was without effect in the absence of
      diazepam, of either of the selective PDE 3 inhibitors milrinone or SK&F 94120,
      but not in the presence of the selective PDE 4 inhibitor rolipram. 4. This effect
      of diazepam was not gamma-aminobutyric acid (GABA)-dependent, since it was
      neither mimicked nor potentiated by GABA, and was not affected by either a high
      concentration (5 microM) of the antagonists of the benzodiazepine/GABA/channel
      chloride receptor complex, picrotoxin, flumazenil and beta-carboline-3-carboxylic
      acid methyl ester (betaCCMe), or by the inverse agonists, beta-carboline-3
      carboxylic acid N-methylamide (betaCCMa) and methyl 6,7-dimethoxy-4-ethyl-beta
      carboline-3-carboxylate (DMCM, 0.1 microM). Furthermore, a specific antagonist of
      the peripheral benzodiazepine receptors, PK 11195 (5 microM), did not influence
      the effect of diazepam. 5. Biochemical studies with isolated PDEs, confirmed that
      diazepam selectively inhibits type 4 PDE from guinea-pig right ventricle rather
      than the other PDEs present in that tissue. The compound inhibited this enzyme in
      a non-competitive manner. Diazepam was also able to inhibit PDE 5, the cyclic GMP
      specific PDE absent from cardiac muscle, with a potency close to that shown for
      PDE 4. 6. Diazepam displaced the selective type 4 PDE inhibitor, rolipram from
      its high affinity binding site in rat brain cortex membranes, and also
      potentiated the rise in cyclic AMP levels induced by isoprenaline in guinea-pig
      eosinophils, where only type 4 PDE is present. 7. The PDE inhibitory properties
      of diazepam were shared, although with lower potency, by other structurally
      related benzodiazepines, that also displaced [3H]-rolipram from its high affinity
      binding site. The order of potency found for these compounds in these assays was
      not related to their potencies as modulators of the GABA receptor through its
      benzodiazepine binding site. 8. The pharmacological and biochemical data
      presented in this study indicate that diazepam behaves as a selective type 4 PDE
      inhibitor in cardiac tissue and this effect seems neither to be mediated by the
      benzodiazepine/GABA/channel chloride receptor complex nor by peripheral type
      benzodiazepine receptors.

PMID- 9559886
TI  - Myogenic nitric oxide synthase activity in canine lower oesophageal sphincter:
      morphological and functional evidence.
AB  - 1. Studies on canine lower oesophageal sphincter (LOS) evaluated the existence
      and function of a myogenic, nitric oxide synthase (NOS) by use of
      immunocytochemistry for NOS isozymes, NADPH-d histochemistry, [3H]-L-arginine to
      [3H]-L-citrulline transformation. In addition, functional studies in the muscle
      bath were performed. 2. Smooth muscle bundles or freshly isolated smooth muscle
      cells of LOS were NADPH-d reactive but did not recognize some antibodies against
      neural, endothelial or inducible NOS. NADPH-d reactivity and immunoreactivity to
      a neural NOS antibody were colocalized in LOS enteric nerves. Muscle plasma
      membrane-enriched fractions from fresh and cultured LOS cells converted [3H]-L
      arginine to [3H]-L-citrulline; activity was mostly Ca2+/calmodulin-dependent. 3.
      N-Nitro-L-arginine (L-NOARG) persistently increased tone (blocked by L-arginine)
      in muscle strips despite blockade of nerve function. Nifedipine prevented or
      abolished L-NOARG-induced, but not carbachol-induced, contraction showing that
      tone increase by L-NOARG required functional L-Ca channels. 4. Membrane-bound,
      myogenic NOS in canine LOS may release NO continuously when Ca2+ entry through L
      Ca channels occurs under physiological conditions and thereby modulate tone in
      LOS.

PMID- 9559887
TI  - Elevated plasma endothelin-1 level in streptozotocin-induced diabetic rats and
      responsiveness of the mesenteric arterial bed to endothelin-1.
AB  - 1. Both the plasma endothelin-1 (ET-1) levels and the plasma glucose levels were
      markedly elevated in streptozotocin (STZ)-induced diabetic rats. 2. The maximum
      contractile response of the mesenteric arterial bed to ET-1 was significantly
      reduced, and the vasodilatation induced by the ET(B)-receptor agonist IRL-1620 in
      the mesenteric arterial bed was significantly reduced in STZ-induced diabetic
      rats. 3. ET-1 (10(-8) M) caused a transient vasodilatation followed by a marked
      vasoconstriction in methoxamine-preconstricted mesenteric arterial beds. The ET-1
      induced vasodilatation was significantly larger in beds from diabetic rats than
      in those from age-matched controls. By contrast, the ET-1-induced
      vasoconstriction was significantly smaller in STZ-induced diabetic rats than in
      the controls. 4. Both removal of the endothelium with Triton X-100 and
      preincubation with BQ-788 (10(-6) M) (ET(B)-receptor antagonist) abolished the ET
      1-induced vasodilatation. Preincubation with BQ-485 (10(-6) M) or BQ-123 (3 x 10(
      6)) (ET(A)-receptor antagonist) significantly augmented the ET-1-induced
      vasodilatation in control mesenteric arterial beds, but not that in beds from
      diabetic rats. 5. These results demonstrate that marked increases not only in
      plasma glucose, but also in plasma ET-1 occur in STZ-induced diabetic rats. We
      suggest that the decreased contractile response and the increased vasodilator
      response of the mesenteric arterial bed to ET-1 may both be due to
      desensitization of ET(A) receptors, though ET(B) receptors may also be
      desensitized. This desensitization may result from the elevation of the plasma ET
      1 levels seen in STZ-induced diabetic rats.

PMID- 9559889
TI  - Influence of potassium channel modulators on cognitive processes in mice.
AB  - 1. The effect of i.c.v. administration of different potassium channel openers
      (minoxidil, pinacidil, cromakalim) and potassium channel blockers
      (tetraethylammonium, apamin, charybdotoxin, gliquidone, glibenclamide) on memory
      processes was evaluated in the mouse passive avoidance test. 2. The
      administration of minoxidil (10 microg per mouse i.c.v.), pinacidil (5-25 microg
      per mouse i.c.v.) and cromakalim (10-25 microg per mouse i.c.v.) immediately
      after the training session produced an amnesic effect. 3. Tetraethylammonium
      (TEA; 1-5 microg per mouse i.c.v.), apamin (10 ng per mouse i.c.v.),
      charybdotoxin (1 microg per mouse i.c.v.), gliquidone (3 microg per mouse i.c.v.)
      and glibenclamide (1 microg per mouse i.c.v.), administered 20 min before the
      training session, prevented the potassium channel opener-induced amnesia. 4. At
      the highest effective doses, none of the drugs impaired motor coordination, as
      revealed by the rota rod test, or modified spontaneous motility and inspection
      activity, as revealed by the hole board test. 5. These results suggest that the
      modulation of potassium channels plays an important role in the regulation of
      memory processes. On this basis, the potassium channel blockers could be useful
      in the treatment of cognitive deficits.

PMID- 9559888
TI  - Induction of nitric oxide synthase in vivo and cell injury in rat duodenal
      epithelium by a water soluble extract of Helicobacter pylori.
AB  - 1. Helicobacter pylori (Hp) infection, which involves the gastric antrum and
      duodenal mucosa, may be involved in peptic ulceration by stimulating the local
      release of cytoxic or pro-inflammatory factors. 2. Nitric oxide (NO) is known to
      be cytotoxic at high concentration. The aim of the present study was therefore to
      investigate the ability of a water soluble extract of Hp to induce NO synthase in
      duodenal mucosa and epithelial cells following its administration in vivo in rats
      and determine its association with cell damage. 3. Administration of Hp water
      extract (4 ml kg(-1)) led to the expression of the calcium-independent inducible
      nitric oxide synthase (iNOS) after 4 h in the duodenum, determined as [14C]
      arginine conversion to citrulline. 4. This iNOS activity was not reduced by
      pretreatment with anti-neutrophil serum (0.4 ml kg(-1), i.p., 3 h before
      challenge). However, dexamethasone pretreatment (1 mg kg(-1), i.v., 2 h before
      the extract), or administration of the NO synthase inhibitor N(G)-nitro-L
      arginine methyl ester (L-NAME, 5 mg kg(-1), i.v., 2.5 h after the extract)
      reduced this activity. 5. Furthermore, iNOS was expressed in duodenal isolated
      epithelial cells 4 h after the i.v. challenge with the extract, at a time when
      the cellular viability was also reduced, as assessed by trypan blue exclusion. 6.
      Dexamethasone pretreatment, administration of L-NAME, or pretreatment with
      polymyxin B (1 mg kg(-1), i.v.) which binds endotoxin, reduced both the iNOS
      activity and epithelial cell damage. 7. The induction of NO synthase by the Hp
      extract thus results in duodenal epithelial cell injury and such actions could
      play a role in pathogenesis of peptic ulcer disease.

PMID- 9559890
TI  - Resistance to myocardial infarction induced by heat stress and the effect of ATP
      sensitive potassium channel blockade in the rat isolated heart.
AB  - 1. Heat stress (HS) is known to protect against myocardial ischaemia-reperfusion
      injury by improving mechanical dysfunction and decreasing necrosis. However, the
      mechanisms responsible for this form of cardioprotection remain to be elucidated.
      ATP-sensitive potassium (K(ATP)) channels have been shown to be involved in the
      delayed phase of protection following ischaemic preconditioning, a phenomenon
      closely resembling the HS-induced cardioprotection. The aim of this study was
      thus to investigate the role of K(ATP) channels in HS-induced protection of the
      isolated rat heart. 2. Twenty four hours after whole body heat stress (at 42
      degrees C for 15 min) or sham anaesthesia, isolated perfused hearts were
      subjected to a 15 min stabilization period followed by a 15 min infusion of
      either 10 microM glibenclamide (Glib), 100 microM sodium 5-hydroxydecanoate (5HD)
      or vehicle (0.04% DMSO). Regional ischaemia (35 min) and reperfusion (120 min)
      were then performed. 3. Prior heat stress significantly reduced infarct-to-risk
      ratio (from 42.4+/-2.4% to 19.4+/-2.9, P<0.001). This resistance to myocardial
      infarction was abolished in both Glib-treated (40.1+/-1.8% vs 42.3+/-1.8%) and
      5HD-treated (41.2+/-1.8% vs 41.8+/-1.2%) groups. 4. The results of this study
      suggest that K(ATP) channel activation contributes to the cytoprotective response
      induced by heat stress.

PMID- 9559891
TI  - Effect of 17beta-oestradiol on cytokine-induced nitric oxide production in rat
      isolated aorta.
AB  - 1. Studies were performed on isolated aortic rings without endothelium to
      investigate the effect of 17beta-oestradiol on cytokine-induced nitric oxide
      production by the inducible nitric oxide synthase (iNOS). 2. Treatment of the
      isolated aortic rings with interleukin-1beta (IL-1beta, 20 micro ml(-1)) led to
      the expression of iNOS mRNA and protein, as well as significant nitrite
      accumulation in the incubation media and suppression of phenylephrine (1 nM-10
      microM)-evoked contraction. 3. Cycloheximide (1 microM), a protein synthesis
      inhibitor, prevented iNOS protein expression, nitrite accumulation and the
      suppression of contractility by IL-1beta on the isolated aortic rings. 17Beta
      oestradiol (1 nM-10 microM) and the partial oestrogen receptor agonist 4-OH
      tamoxifen (1 nM-10 microM) produced concentration-dependent inhibition of IL
      1beta-induced nitrite accumulation and restored vasoconstrictor responsiveness to
      phenylephrine, similar to the iNOS inhibitor aminoguanidine (100 microM). 4.
      Semiquantitative PCR demonstrated decreased iNOS mRNA in the IL-1beta-induced and
      17beta-oestradiol-treated rings. Western blot analysis of rat aorta homogenates
      revealed that 17beta-oestradiol treatment resulted in a reduction in IL-1beta
      induced iNOS protein level. 5. Incubation with tumour necrosis factor alpha (TNF
      alpha, 1 ng ml(-1)) resulted in significant nitrite accumulation in the
      incubation media and suppression of the smooth muscle contractile response to
      phenylephrine, similar to IL-1beta. The effects of TNF alpha were also inhibited
      by co-incubation of the rings with 17beta-oestradiol and 4-OH-tamoxifen (1
      microM). 6. The anti-transforming growth factor-beta1 (TGF-beta1) antibody, which
      inhibited TGF-beta1-induced suppression of nitrite production from IL-1beta
      treated vascular rings, did not affect the inhibitory action of 17beta
      oestradiol, suggesting that the effect of oestrogen on iNOS inhibition was not
      mediated by TGF-beta1. 7. These results show that the ovarian sex steroid, 17beta
      oestradiol is a modulator of cytokine-induced iNOS activity in rat vascular
      smooth muscle and its mechanism of action involves decrease of iNOS mRNA and
      protein.

PMID- 9559892
TI  - The possible mechanisms of the antiproliferative effect of fullerenol,
      polyhydroxylated C60, on vascular smooth muscle cells.
AB  - 1. The possible mechanisms of the antiproliferative effect of polyhydroxylated
      fullerene (fullerenol), a novel free radical trapper, were studied in rat
      vascular smooth muscle cells (A7r5 cells) and compared with the effect of
      ascorbic acid. 2. Fullerenol-1 and ascorbic acid inhibited the proliferative
      responses in a number of cells, including rat aortic smooth muscle cells (A7r5
      cells), human coronary artery smooth muscle cells, and human CEM lymphocytes (CEM
      cells) in a concentration dependent manner. 3. At the concentration range of 10(
      6) to 10(-2) M, fullerenol-1 and ascorbic acid concentration-dependently
      inhibited the proliferative responses stimulated by serum in A7r5 cells.
      Fullerenol-1 was more potent than ascorbic acid. 4. The production of O2- induced
      by alloxan, a diabetogenic compound, was reduced by fullerenol-1 (10(-4) M) in
      the presence of A7r5 cells. 5. The cytosolic protein kinase C activity of A7r5
      cells stimulated by phorbol ester was reduced by 10(-3) M fullerenol-1, but not
      ascorbic acid (10(-4)-10(-2) M) and fullerenol-1 at lower concentrations (10(-6)
      10(-4) M). 6. In contrast, the membraneous protein tyrosine kinase activity of
      A7r5 cells stimulated by foetal calf serum was significantly reduced by
      fullerenol-1 (10(-6)-10(-3) M) and ascorbic acid (10(-4)-10(-2) M). Again, the
      inhibitory activity of fullerenol-1 was greater than that of ascorbic acid. 7.
      Our results demonstrate that fullerenol-1 and ascorbic acid exhibit inhibitory
      effects on transduction signals in addition to their antioxidative property. It
      is suggested that the antiproliferative effect of fullerenol-1 on vascular smooth
      muscle cells may partly be mediated through the inhibition of protein tyrosine
      kinase.

PMID- 9559893
TI  - Characterization of K(ATP) channels in intact mammalian skeletal muscle fibres.
AB  - 1. The aim of this study was to characterize the K(ATP) channel of intact rat
      skeletal muscle (rat flexor digitorum brevis muscle). Changes in membrane
      currents were recorded with two-electrode voltage-clamp of whole fibres. 2. The
      K(ATP) channel openers, levcromakalim and pinacidil (10-400 microM), caused a
      concentration-dependent increase in whole-cell chord conductance (up to
      approximately 1.5 mScm(-2)). The activated current had a weak inwardly rectifying
      current-voltage relation, a reversal potential near E(K) and nanomolar
      sensitivity to glibenclamide--characteristic of a K(ATP) channel current.
      Concentration-effect analysis revealed that levcromakalim and pinacidil were not
      particularly potent (EC50 approximately 186 microM, approximately 30 microM,
      respectively), but diazoxide was completely inactive. 3. The ability of both
      classical K(ATP) channel inhibitors (glibenclamide, tolbutamide, glipizide and 5
      hydroxydecanoic acid) and a number of structurally related glibenclamide
      analogues to antagonize the levcromakalim-induced current was determined.
      Glibenclamide was the most potent compound with an IC50 of approximately 5 nM.
      However, the non-sulphonylurea (but cardioactive) compound 5-hydroxydecanoic acid
      was inactive in this preparation. 4. Regression analysis showed that the
      glibenclamide analogues used have a similar rank order of potency to that
      observed previously in vascular smooth muscle and cerebral tissue. However, two
      compounds (glipizide and DK13) were found to have unexpectedly low potency in
      skeletal muscle. 5. These experiments revealed K(ATP) channels of skeletal muscle
      to be at least 10x more sensitive to glibenclamide than previously found; this
      may be because of the requirement for an intact intracellular environment for the
      full effect of sulphonylureas to be realised. Pharmacologically, K(ATP) channels
      of mammalian skeletal muscle appear to resemble most closely K(ATP) channels of
      cardiac myocytes.

PMID- 9559894
TI  - Desensitization and resensitization of delta-opioid receptor-mediated Ca2+
      channel inhibition in NG108-15 cells.
AB  - 1. To approach the mechanisms underlying desensitization of the opioid receptor
      mediated Ca2+ channel inhibition, the effects of prolonged application of [D
      Ala2, D-Leu5]enkephalin (DADLE) on Ba2+ currents (I(Ba)) through Ca2+ channels
      were analysed in NG108-15 neuroblastoma x glioma hybrid cells. 2. Inhibition of
      I(Ba) by 100 nM DADLE desensitized by 57% with a time constant of 4.4 min. 3.
      Maximal desensitization of the delta-opioid receptor-Ca2+ channel coupling was
      attained by 1 microM DADLE. The EC50 value for desensitization was estimated to
      be 78 nM. 4. RNA blot hybridization analysis and immunoblot analysis revealed the
      expression of beta-adrenoceptor kinase-1 (betaARK1) in NG108-15 cells. 5.
      Heparin, an inhibitor of betaARK, significantly reduced the magnitude and rate of
      desensitization, whereas Rp-cyclic AMPS and PKI (14-24)amide, inhibitors of
      cyclic AMP-dependent protein kinase (PKA), or long-term treatment with phorbol 12
      myristate 13-acetate to induce down-regulation of protein kinase C (PKC) had no
      significant effect. 6. Recovery from desensitization (resensitization) proceeded
      with a time constant of 6.7 min. Okadaic acid, an inhibitor of serine/threonine
      phosphatases 1 and 2A, significantly attenuated the degree of resensitization. 7.
      In summary, we have characterized the time course and concentration-dependence of
      the desensitization of DADLE-induced I(Ba) inhibition in NG108-15 cells. This
      desensitization was reversible after removal of DADLE. It is suggested that
      betaARK, but neither PKA nor PKC, is involved in desensitization, while
      serine/threonine phosphatases mediate resensitization.

PMID- 9559895
TI  - A comparison of the effects of L-NAME, 7-NI and L-NIL on carrageenan-induced
      hindpaw oedema and NOS activity.
AB  - 1. Intraplantar injection of carrageenan (150 microl, 1-3% w/v) in the rat
      resulted in a dose-related increase in hindpaw weight (oedema) characterized by a
      rapid 'early' phase (up to 2.5 h) response followed by a more sustained 'late'
      phase (2-6 h) response. No change in weight of either the contralateral (i.e.
      noninjected) hindpaw or hindpaws injected with saline was observed. 2. Six hours
      after intraplantar injection of carrageenan (1-3% w/v) hindpaw constitutive (i.e.
      calcium-dependent) nitric oxide synthase (cNOS) activity (determined ex vivo as
      the conversion of radiolabelled L-arginine to radiolabelled citrulline) was
      increased (e.g. 2% w/v; 0.64+/-0.08 pmol citrulline mg(-1) protein 15 min(-1)
      c.f. 0.08+/-0.04 pmol citrulline mg(-1) protein 15 min(-1) in saline-injected,
      control animals, n=4, P<0.05). Carrageenan injection also resulted in the
      appearance in hindpaw homogenates of inducible (i.e. calcium-independent) nitric
      oxide synthase (iNOS, e.g. 2% w/v; 0.67+/-0.14 pmol citrulline mg(-1) protein 15
      min(-1), n=4). Hindpaw cyclic GMP concentration was also significantly increased
      6 h after intraplantar injection of carrageenan (e.g. 2% w/v; 379.6+/-26.8 fmol
      mg(-1) protein c.f. 261.8+/-42.2 fmol mg(-1) protein, in saline-injected, control
      animals, n=4, P<0.05). 3. Pretreatment (5-25 mg kg(-1), i.p., 30 min before
      carrageenan, 2% w/v) of animals with L-N(G) nitro arginine methyl ester (L-NAME;
      isoform nonselective inhibitor of NOS) or 7-nitro indazole (7-NI; inhibitor of
      neuronal NOS, nNOS) caused dose-related inhibition of both the early (2 h) and
      late (6 h) phase hindpaw oedema, associated with reduced hindpaw iNOS and cNOS
      activity and cyclic GMP concentration in animals killed at 6 h. Administration of
      7-NI (5-25 mg kg(-1), i.p.) to animals 2.5 h after intraplantar carrageenan (2%
      w/v) injection (i.e. at the end of the early phase oedema response) produced dose
      related inhibition of the late phase response. 4. Pretreatment (5-25 mg kg(-1),
      i.p., 30 min before carrageenan, 2% w/v) of animals with L-N6-iminoethyllysine (L
      NIL, selective inhibitor of iNOS) (5-25 mg kg(-1)) failed to affect the early
      phase hindpaw oedema response but did produce a dose-related inhibition of the
      late phase oedema. L-NIL pretreatment also inhibited the carrageenan-induced
      increase in both hindpaw iNOS and cNOS activity as well as the rise in hindpaw
      cyclic GMP concentration. 5. The present experiments demonstrate an anti
      inflammatory effect of 7-NI as evidenced by inhibition of carrageenan-induced
      hindpaw oedema in the rat. Inhibition of nNOS (early phase) and iNOS (late phase)
      at the site of inflammation most probably accounts for the anti-inflammatory
      activity observed. These data suggest a role for nitric oxide synthesized by the
      nNOS isoform (most probably within sensory nerves) in this model of inflammation.

PMID- 9559896
TI  - Effects of bradykinin on signal transduction, cell proliferation, and cytokine,
      prostaglandin E2 and collagenase-1 release from human corneal epithelial cells.
AB  - 1. We recently demonstrated the presence of phospholipase C-coupled bradykinin
      (BK) B2-receptors in human primary and SV40 virus-immortalized corneal epithelial
      (CEPI) cells. 2. The aims of the present studies were to demonstrate the specific
      binding of [3H]-BK to CEPI cell membranes and to study its pharmacological
      characteristics. In addition, we wished to study the functional coupling of the
      BK receptors to various physiological and pathological mechanisms in the CEPI
      cells, including phosphoinositide (PI) turnover, intracellular Ca2+-mobilization
      ([Ca2+]i), cell proliferation (via [3H]-thymidine incorporation), and the release
      of various cytokines, collagenase-1 (matrix metalloproteinase-1) and
      prostaglandin E2 (PGE2). 3. Specific [3H]-BK binding comprised 83 +/- 2% of the
      total binding, and was of high affinity (Kd = 1.66 +/- 0.52 nM, n = 5), saturable
      (Bmax = 640 +/- 154 fmol g(-1) wet weight) and reversible. Competition studies
      yielded the following affinity values for BK and a number of BK-related peptides:
      Hoe-140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]BK; icatibant): Ki = 0.17 +/- 0.07 nM; BK:
      Ki = 1.0 +/- 0.11 nM; [Tyr8]-BK: Ki = 12.9 +/- 2.3 nM; [des-Arg9]-BK: Ki > 9,200
      nM (all n = 3-5)). 4. BK potently stimulated PI turnover (EC50 = 2.3 +/- 0.3 nM;
      n = 7) and [Ca2+]i mobilization (EC50 = 8-20 nM) in CEPI cells and both responses
      were inhibited in a concentration-dependent manner by 100 nM-10 microM Hoe-140, a
      selective B2-receptor antagonist, and also inhibited by the selective
      phospholipase C (PLC) inhibitor, U73122 (1-(6-((17beta-3-methoxyestra-1,3,5(10)
      trien-17-yl)amino)hexyl)-1 H-pyrrole-2,5-dione) (IC50 = 3.0 +/- 1.6 microM). BK
      induced [Ca2+]i mobilization was reduced by about 30% in the presence of 4 mM
      EGTA, but was not significantly affected by 100 nM nifedipine. 5. BK (0.1 nM-10
      microM) significantly (P<0.05-0.001) stimulated [3H]-thymidine incorporation into
      CEPI cellular DNA. However, while interleukin-1alpha (IL-1alpha; 10 ng ml(-1))
      potently stimulated the release of IL-6, IL-8 and granulocyte macrophage colony
      stimulating factor from CEPI cells, BK (0.1 nM-10 microM) was without effect. 6.
      Whilst phorbol-12-myristate-13-acetate (PMA; 3 microg ml(-1)) and 10% foetal
      bovine serum (positive control agents) significantly stimulated the release of
      both MMP-1 and PGE2 from CEPI cells, BK (0.1 nM-10 microM) was without any
      significant effect under these conditions. 7. In conclusion, these data indicate
      that the CEPI cells express high-affinity [3H]-BK binding sites representing B2
      subtype BK receptors coupled to PI turnover and [Ca2+]i mobilization which appear
      to stimulate [3H]-thymidine incorporation into cellular DNA. In contrast, BK
      failed to elicit the release of PGE2, various cytokines and MMP-1 from CEPI
      cells. These results suggest that BK may have a potential role in corneal
      epithelium wound healing by stimulating cell proliferation.

PMID- 9559897
TI  - Effect of RX 821002 at 5-HT1A-receptors in rabbit spinal cord in vivo.
AB  - 1. The activity of RX 821002 (2-methoxy idazoxan) at 5-HT1A-receptors in the
      spinal cord has been investigated in decerebrated, spinalized rabbits. Reflexes
      evoked in medial gastrocnemius motoneurones by electrical stimulation of the
      sural nerve were unaffected by intrathecal (i.th.) administration of RX 821002
      (111 and 664 nmol cumulative, n = 7), although the highest dose of this drug did
      produce a significant increase in heart rate of 28 +/- 7 beats min(-1).
      Subsequent administration of the 5-HT1A-receptor agonist (+/-)-8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) at 300 nmol, i.th., facilitated reflexes to a
      median of 144% of pre-drug controls, an effect that was partially reversed (to a
      median value of 120% of pre-drug values) by subsequent administration of the 5
      HT1A-receptor antagonist WAY-100635, at 185 nmol i.th. 2. In a separate set of
      experiments, 8-OH-DPAT was given at 30 nmol i.th. and potentiated reflexes to a
      median of 170% of pre-drug levels (n = 8). Subsequent administration of RX 821002
      (at a cumulative dose of 1.11 micromol, i.th., n = 5) significantly reduced
      gastrocnemius responses to a median of 154% of control values. 3. After a 3 h
      recovery period, 8-OH-DPAT was re-administered at 30 nmol, i.th., and increased
      reflexes to a median value of 151% of pre-drug levels, an effect not
      significantly different from when it was given alone. WAY-100635 dose-dependently
      antagonized this effect, causing significant reductions in reflexes at a
      cumulative dose of 0.55 nmol, i.th., and complete reversal of the effects of 8-OH
      DPAT at a cumulative dose of 5.5 nmol. 4. These data show that, at intrathecal
      doses up to 664 nmol, RX 821002 is devoid of agonist activity at 5-HT1A
      receptors. It appears to be a very weak antagonist at these sites in vivo, being
      some 2000 times less potent than WAY-100635. The inability of WAY-100635 to block
      completely the effects of high doses of 8-OH-DPAT has been noted previously and
      can be explained by non-selective actions of the agonist. However, it would
      appear that a 30 nmol i.th. dose of 8-OH-DPAT is selective for 5-HT1A receptors
      in this preparation.

PMID- 9559898
TI  - Stretch-evoked inhibition of spontaneous migrating contractions in a whole mount
      preparation of the guinea-pig upper urinary tract.
AB  - 1. The effects of circumferentially-applied stretch on the spontaneous
      contractility of a whole mount preparation of the guinea-pig upper urinary tract
      (UUT) (renal pelvis and ureter) were investigated by use of standard isometric
      tension recording techniques. 2. Simultaneous tension recordings of the proximal
      and distal portions of the renal pelvis (RP) and ureter revealed that spontaneous
      contractions, in 79% (n = 66) of preparations, originated in the proximal RP (at
      a frequency of 4.5 min(-1)) and propagated to the distal RP and ureter at a
      velocity of 1-3 cm s(-1). Pretreatment with tetrodotoxin (TTX) (3-10 microM) or
      N(G)-nitro-L-arginine (100 microM) had little effect on the spontaneous
      contractility of the UUT, motility indexes (MIs) (contraction amplitude x
      contraction frequency) calculated after 20 min exposure were little affected by
      TTX or N(G)-nitro-L-arginine (L-NOARG). Omega-conotoxin GVIA (100 nM)
      significantly reduced MI values in both the proximal RP and ureter. 3. Exposure
      of the spontaneously-active UUT to capsaicin (10 microM for 15 min) induced a
      transient increase in UUT contractility, followed by a prolonged negative
      inotropic effect. The MI values, calculated 60 min after the washout of
      capsaicin, for the proximal and distal RP and ureter were reduced to 56%, 53% (n
      = 18) and 61% (n = 16), respectively, of their control values. This capsaicin
      pretreatment blocked the positive inotropic effects of transmural electrical
      nerve stimulation on UUT contractility to reveal a small inhibitory effect which
      was readily blocked by tetrodotoxin (3 microM) (n = 3). The excitatory and
      inhibitory actions of nerve stimulation were both blocked by TTX (3 microM). 4. A
      second exposure to capsaicin (10 microM for 15 min), further reduced the MI
      values (calculated 60 min after washout) in the proximal and distal RP to 41% and
      31%, respectively (n = 6; P<0.05), of the initial control values. 5. In 61% (n =
      99) of preparations, the application of stretch to the proximal RP (0.5 to 2 mm)
      evoked a decrease in the amplitude of the contractions recorded in the distal RP,
      but not in the ureter. Stretch applied to the distal RP or ureter had no effect
      on the contractions recorded in the other regions of the UUT. 6. In 5 out of 6
      preparations, a single application of capsaicin (10 microM for 15 min) had little
      effect on the change in contractile force of the distal RP evoked upon stretch of
      the proximal RP. 7. The inhibition of the distal RP upon stretch of the proximal
      RP was partially reduced (P<0.05) when the UUT was pretreated with the calcitonin
      gene-related peptide (CGRP) receptor antagonist, hCGRP (8-37) (1 microM). 8. The
      application of the CGRP receptor agonist, hCGRP (100 nM) inhibited contractility
      in the UUT in a region dependent manner. The MI of the proximal RP was decreased
      32% after 6 min; while the MIs of the distal RP and ureter were reduced 83% and
      63%, respectively, within 5 min of the application of hCGRP. 9. Glibenclamide (1
      microM) had little effect on the spontaneous contractility of the UUT, but
      significantly reduced the inhibition of the distal RP evoked upon stretch (0.5 to
      2 mm) of the proximal RP. TTX (3-10 microM), L-NOARG (100 microM) or omega
      conotoxin GVIA (100 nM) had little effect on the stretch-evoked inhibition of the
      distal RP. 10. It was concluded that circumferential stretch of the proximal RP
      inhibits the contractility of the distal RP and that a component of this
      inhibition involves the activation of a glibenclamide-sensitive mechanism via the
      release of endogenous CGRP, possibly from the varicosities of intramural sensory
      nerves.

PMID- 9559900
TI  - Effect of nitrovasodilators and inhibitors of nitric oxide synthase on ischaemic
      and reperfusion function of rat isolated hearts.
AB  - 1. The functional role of the nitric oxide (NO)/guanosine 3':5'-cyclic
      monophosphate (cyclic GMP) pathway in experimental myocardial ischaemia and
      reperfusion was studied in rat isolated hearts. 2. Rat isolated hearts were
      perfused at constant pressure with Krebs-Henseleit buffer for 25 min (baseline),
      then made ischaemic by reducing coronary flow to 0.2 ml min(-1) for 25 or 40 min,
      and reperfused at constant pressure for 25 min. Drugs inhibiting or stimulating
      the NO/cyclic GMP pathway were infused during the ischaemic phase only. Ischaemic
      contracture, myocardial cyclic GMP and cyclic AMP levels during ischaemia, and
      recovery of reperfusion mechanical function were monitored. 3. At baseline, heart
      rate was 287+/-12 beats min(-1), coronary flow was 12.8+/-0.6 ml min(-1), left
      ventricular developed pressure (LVDevP) was 105+/-4 mmHg and left ventricular end
      diastolic pressure 4.6+/-0.2 mmHg in vehicle-treated hearts (control; n=12).
      Baseline values were similar in all treatment groups (P>0.05). 4. In normoxic
      perfused hearts, 1 microM N(G)-nitro-L-arginine (L-NOARG) significantly reduced
      coronary flow from 13.5+/-0.2 to 12.1+/-0.1 ml min(-1) (10%) and LVDevP from 97+/
      1 to 92+/-1 mmHg (5%; P<0.05, n=5). 5. Ischaemic contracture was 46+/-2 mmHg,
      i.e. 44% of LVDevP in control hearts (n=12), unaffected by low concentrations of
      nitroprusside (1 and 10 microM) but reduced to approximately 30 mmHg
      (approximately 25%) at higher concentrations (100 or 1000 microM; P<0.05 vs
      control, n=6). Conversely, the NO synthase inhibitor L-NOARG reduced contracture
      at 1 microM to 26+/-3 mmHg (23%), but increased it to 63+/-4 mmHg (59%) at 1000
      microM (n=6). Dobutamine (10 microM) exacerbated ischaemic contracture (81+/-3
      mmHg; n = 7) and the cyclic GMP analogue Sp-8-(4-p-chlorophenylthio)-3',5'
      monophosphorothioate (Sp-8-pCPT-cGMPS; 10 microM) blocked this effect (63+/-11
      mmHg; P<0.05 vs dobutamine alone, n=5). 6. At the end of reperfusion, LVDevP was
      58+/-5 mmHg, i.e. 55% of pre-ischaemic value in control hearts, significantly
      increased to approximately 80% by high concentrations of nitroprusside (100 or
      1000 microM) or L-NOARG at 1 microM, while a high concentration of L-NOARG (1000
      microM) reduced LVDevP to approximately 35% (P<0.05 vs control; n=6). 7.
      Ischaemia increased tissue cyclic GMP levels 1.8 fold in control hearts (P<0.05;
      n=12); nitroprusside at 1 microM had no sustained effect, but increased cyclic
      GMP approximately 6 fold at 1000 microM; L-NOARG (1 or 1000 microM) was without
      effect (n=6). Nitroprusside (1 or 1000 microM) marginally increased cyclic AMP
      levels whereas NO synthase inhibitors had no effect (n=6). 8. In conclusion, the
      cardioprotective effect of NO donors, but not of low concentrations of NO
      synthase inhibitors may be due to their ability to elevate cyclic GMP levels.
      Because myocardial cyclic GMP levels were not affected by low concentrations of
      NO synthase inhibitors, their beneficial effect on ischaemic and reperfusion
      function is probably not accompanied by reduced formation of NO and peroxynitrite
      in this model.

PMID- 9559899
TI  - Effect of the triaminopyridine flupirtine on calcium uptake, membrane potential
      and ATP synthesis in rat heart mitochondria.
AB  - 1. Flupirtine is an analgesic agent which exhibits neuronal cytoprotective
      activity and may have value in the treatment of conditions involving cell injury
      and apoptosis. Since flupirtine has no action on known receptor sites we have
      investigated the effect of this drug on mitochondrial membrane potential, and the
      changes in intramitochondrial calcium concentration in particular. 2. The
      findings show that flupirtine increases Ca2+ uptake in mitochondria in vitro. At
      clinically relevant flupirtine concentrations, corresponding to flupirtine levels
      in vitro of 0.2 to 10 nmol mg(-1) mitochondrial protein, there was a 2 to 3 fold
      increase in mitochondrial calcium levels (P<0.01). At supra-physiological
      flupirtine concentrations of 20 nmol mg(-1) mitochondrial protein and above, the
      mitochondrial calcium concentrations were indistinguishable from those in
      untreated mitochondria. 3. Mitochondrial membrane potential closely paralleled
      the changes in mitochondrial calcium levels showing a 20% (P<0.01) increase when
      the flupirtine concentration was raised from 0.2 nmol to 10 nmol mg(-1)
      mitochondrial protein and a return to control values at 20 nmol mg(-1) protein.
      4. The increase in mitochondrial calcium uptake and membrane potential were
      accompanied by an increase in mitochondrial ATP synthesis (30%; P<0.05) and a
      similar percentage reduction in mitochondrial volume. 5. Calcium at 80 and 160
      nmol mg(-1) mitochondrial protein decreased ATP synthesis by 20-25% (P<0.001).
      This decrease was prevented or diminished if flupirtine at 10 nmol mg(-1) protein
      was added before the addition of calcium. 6. Since intracellular levels of
      flupirtine in intact cells never exceeded 10 nmol mg(-1) mitochondrial protein,
      these findings are supportive evidence for an in vivo cytoprotective action of
      flupirtine at the mitochondrial level.

PMID- 9559901
TI  - Early effects of acute gamma-radiation on vascular arterial tone.
AB  - 1. To determine the acute effects of irradiation on the functionality of vessel,
      rat aortic rings were mounted in an organ bath for isometric tension measurements
      and irradiated (60Co, 1 Gy min(-1), 15 min). 2. Irradiation, which is without
      effect on non-contracted or endothelium-denuded vessels, led to an immediate and
      reversible increase in vascular tone on (-)-phenylephrine (1 microM)
      precontracted aortic rings. The tension reached a plateau about 5 min after the
      beginning of irradiation. 3. The maximal radiation-induced contraction occurred
      on aortic rings relaxed by acetylcholine (ACh) (1 microM). In this condition, the
      addition of catalase (1000 u ml(-1)), which reduces hydrogen peroxide, and DMSO
      (0.1% v/v), which scavenges hydroxyl radical, had no influence on tension level
      while superoxide dismutase (SOD) (100 u ml(-1)), a superoxide anion scavenger,
      reduced the observed contraction. A similar result was obtained in the presence
      of indomethacin (10 microM), a cyclo-oxygenase blocker. 4. Pretreatment of rings
      with the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester
      (L-NAME) (10-100 microM) inhibited the radiation-induced contraction. 5. This
      effect was dose rate-dependent and even occurred for a very low dose rate (0.06
      Gy min(-1)). 6. The present results indicate that gamma-radiation induces an
      instantaneous vascular tone increase that is endothelium and dose rate-dependent.
      This effect is (i) maximal when nitric oxide (NO) is produced, (ii) greatly
      reduced by SOD and (iii) inhibited by L-NAME, suggesting a major involvement of
      complexes between NO and superoxide anion.

PMID- 9559902
TI  - Pharmacological comparison of UTP- and thapsigargin-induced arachidonic acid
      release in mouse RAW 264.7 macrophages.
AB  - 1. Although stimulation of mouse RAW 264.7 macrophages by UTP elicits a rapid
      increase in intracellular free Ca2+ ([Ca2+]i), phosphoinositide (PI) turnover,
      and arachidonic acid (AA) release, the causal relationship between these
      signalling pathways is still unclear. In the present study, we investigated the
      involvement of phosphoinositide-dependent phospholipase C (PI-PLC) activation,
      Ca2+ increase and protein kinase activation in UTP-induced AA release. The
      effects of stimulating RAW 264.7 cells with thapsigargin, which cannot activate
      the inositol phosphate (IP) cascade, but results in the release of sequestered
      Ca2+ and an influx of extracellular Ca2+, was compared with the effects of UTP
      stimulation to elucidate the multiple regulatory pathways for cPLA2 activation.
      2. In RAW 264.7 cells UTP (100 microM) and thapsigargin (1 microM) caused 2 and
      1.2 fold increases, respectively, in [3H]-AA release. The release of [3H]-AA
      following treatment with UTP and thapsigargin were non-additive, totally
      abolished in the Ca2+-free buffer, BAPTA (30 microM)-containing buffer or in the
      presence of the cPLA2 inhibitor MAFP (50 microM), and inhibited by pretreatment
      of cells with pertussis toxin (100 ng ml(-1)) or 4-bromophenacyl bromide (100
      microM). By contrast, aristolochic acid (an inhibitor of sPLA2) had no effect on
      UTP and thapsigargin responses. 3. U73122 (10 microM) and neomycin (3 mM),
      inhibitors of PI-PLC, inhibited UTP-induced IP formation (88% and 83% inhibition,
      respectively) and AA release (76% and 58%, respectively), accompanied by a
      decrease in the [Ca2+]i rise. 4. Wortmannin attenuated the IP response of UTP in
      a concentration-dependent manner (over the range 10 nM-3 microM), and reduced the
      UTP-induced AA release in parallel. RHC 80267 (30 microM), a specific
      diacylglycerol lipase inhibitor, had no effect on UTP-induced AA release. 5.
      Short-term treatment with PMA (1 microM) inhibited the UTP-stimulated
      accumulation of IP and increase in [Ca2+]i, but had no effect on the release of
      AA. In contrast, the AA release caused by thapsigargin was increased by PMA. 6.
      The role of PKC in UTP- and thapsigargin-mediated AA release was shown by the
      blockade of these effects by staurosporine (1 microM), Ro 31-8220 (10 microM), Go
      6976 (1 microM) and the down-regulation of PKC. 7. Following treatment of cells
      with SK&F 96365 (30 microM), thapsigargin-, but not UTP-, induced Ca2+ influx,
      and the accompanying AA release, were down-regulated. 8. Neither PD 98059 (100
      microM), MEK a inhibitor, nor genistein (100 microM), a tyrosine kinase
      inhibitor, had any effect on the AA responses induced by UTP and thapsigargin. 9.
      We conclude that UTP-induced cPLA2 activity depends on the activation of PI-PLC
      and the sustained elevation of intracellular Ca2+, which is essential for the
      activation of cPLA2 by UTP and thapsigargin. The [Ca2+]i-dependent AA release
      that follows treatment with both stimuli was potentiated by the activity of
      protein kinase C (PKC). A pertussis toxin-sensitive pathway downstream of the
      increase in [Ca2+]i was also shown to be involved in AA release.

PMID- 9559903
TI  - Receptor mechanisms involved in the 5-HT-induced inotropic action in the rat
      isolated atrium.
AB  - 1. The effects of 5-hydroxytryptamine (5-HT) in rat cardiac preparations were
      studied. 5-HT up to 10 microM failed to affect contractility in papillary
      muscles. However, in electrically driven (1 Hz) left atria 5-HT exerted a
      positive inotropic effect that started at 1 microM and attained its maximum at 10
      microM (312+/-50% of predrug value, n=8). 2. 5-HT 10 microM stimulated the
      content of inositol-1,4,5-trisphosphate but not of cyclic AMP in rat left atria.
      3. Plasma and serum levels of 5-HT amounted to about 0.3 microM and 15 microM,
      respectively. 4. The selective 5-HT4 receptor antagonists GR 125487 (10 nM and 1
      microM) and SB 203186 (1 microM) did not attenuate the positive inotropic effect
      of 5-HT in rat left atria. In contrast, the 5-HT2 receptor antagonist ketanserin
      (5 nM, 50 nM, 1 microM) resulted in a concentration-dependent diminution of the
      positive inotropic effect of 5-HT in rat left atria. 5. Reverse transcriptase
      polymerase chain reaction with specific primers detected mRNA of the 5-HT2A
      receptor in rat atria and ventricles, while expression of the 5-HT4 receptor was
      confined to atria. 6. It is suggested that the positive inotropic effect of 5-HT
      in electrically driven rat left atria is mediated by ketanserin-sensitive 5-HT2A
      receptors and not through 5-HT4 receptors.

PMID- 9559904
TI  - Protein kinase C-mediated inhibition of transmembrane signalling through CCK(A)
      and CCK(B) receptors.
AB  - 1. The rat CCK(A) and CCK(B) receptors were stably expressed in Chinese hamster
      ovary (CHO-09) cells in order to compare modes of signal transduction and effects
      of protein kinase C (PKC) thereupon. 2. Spectrofluorophotometry of Fura-2-loaded
      cells revealed that both receptors retained their pharmacological characteristics
      following expression in CHO cells. Sulphated cholecystokinin-(26-33)-peptide
      amide (CCK-8-S) increased the cytosolic Ca2+ concentration ([Ca2+]i) in CCK(A)
      cells, measured as an increase in Fura-2 fluorescence emission ratio, 1000 fold
      more potently than its non-sulphated form (CCK-8-NS) (EC50 values of 0.19 nM and
      0.18 microM, respectively). By contrast, CCK-8-S and CCK-8-NS were equally potent
      in CCK(B) cells (EC50 values of 0.86 nM and 1.18 nM, respectively). The CCK(A)
      receptor agonist JMV-180 increased [Ca2+]i only in CCK(A) cells. Likewise,
      pentagastrin increased [Ca2+]i only in CCK(B) cells. Finally, CCK-8-S-induced
      Ca2+ signalling through the CCK(A) receptor was most potently inhibited by the
      CCK(A) receptor antagonist L364,718, whereas the CCK(B) receptor antagonist
      L365,260 was more potent in CCK(B) cells. 3. Receptor-mediated activation of
      adenylyl cyclase was measured in the presence of the inhibitor of cyclic
      nucleotide phosphodiesterase activity, 3-isobutyl-1-methylxanthine. CCK-8-S and,
      to a lesser extent, CCK-8-NS, but not JMV-180 or pentagastrin, stimulated the
      accumulation of cyclicAMP in CCK(A) cells. By contrast, none of these agonists
      increased cyclicAMP in CCK(B) cells. 4. Short-term (3 min) pretreatment with the
      PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA) evoked a rightward shift
      of the dose-response curve for the Ca2+ mobilizing effect of CCK-8-S in both cell
      lines. In addition, short-term TPA pretreatment markedly reduced CCK-8-S-induced
      cyclicAMP accumulation in CCK(A) cells. In both cases, the inhibitory effect of
      TPA was abolished by the PKC inhibitors, GF-109203X and staurosporine, whereas no
      inhibition was observed with the inactive phorbol ester, 4-alpha-phorbol 12
      myristate 13-acetate. 5. During prolonged TPA treatment, the cells gradually
      recovered from phorbol ester inhibition and in the case of CCK-8-S-induced Ca2+
      mobilization complete recovery was achieved after 24 h of TPA treatment. Western
      blot analysis revealed that this recovery was paralleled by down-regulation of
      PKC-alpha, suggesting the involvement of this PKC isotype in the inhibitory
      action of TPA. 6. This study demonstrates that following expression in CHO cells
      (i) both CCK(A) and CCK(B) receptors are coupled to Ca2+ mobilization, (ii) only
      CCK(A) receptors are coupled to cyclicAMP formation and (iii) with both receptors
      signalling is inhibited by PKC.

PMID- 9559905
TI  - Differential effects of cyclosporine A after acute antigen challenge in
      sensitized cats in vivo and ex vivo.
AB  - 1. We determined the effect of cyclosporine A (CsA) treatment on mast cell
      degranulation and lung resistance (R(L)) in vivo, and tracheal smooth muscle
      (TSM) contraction ex vivo after antigen challenge in sensitized cats. We also
      determined the direct effects of addition of CsA to the tissue bath on antigen
      induced responses of TSM in vitro. 2. Cats (n=10) were sensitized by i.m.
      injection of Ascaris suum antigen (AA); 5 cats (CsA+) received CsA twice daily
      for 2 weeks before acute antigen challenge in doses sufficient to suppress
      interleukin-2 secretion from feline peripheral blood mononuclear cells ex vivo.
      3. Lung resistance increased comparably within 10 min of exposure to AA (P<0.03).
      Histamine content in bronchoalveolar lavage fluid from both groups increased
      comparably within 30 min of antigen challenge, from undetectable levels to 542+/
      74 pg ml(-1) post AA for CsA+ and from 74+/-19 pg ml(-1) at baseline, to 970+/
      180 pg ml(-1) post AA CsA- (P<0.05; P=NS vs CsA+). 4. In excised TSM, active
      tension elicited by exposure to AA in vitro was 107+/-38% KCl in the CsA+ group
      vs 144+/-56% KCl in the CsA- group (P=NS). However, contraction of TSM (n=4)
      harvested from both groups was abolished or greatly diminished after AA challenge
      when tissues were pre-incubated with 1 microM CsA in vitro (8+/-8% KCl, P<0.05 vs
      CsA+ and CsA-). This was associated with inhibited release of 5-hydroxytryptamine
      into the organ bath fluid of tissues treated with CsA in vitro only. 5. We
      demonstrated that CsA treatment in vivo does not inhibit the early phase
      asthmatic response or mast cell degranulation following antigen challenge in
      sensitized cats. Additionally, the effects of CsA on mast cell function ex vivo
      do not reflect lack of effects of CsA on mast cell function in vivo in this
      animal model of atopic asthma.

PMID- 9559907
TI  - Zn2+ modulation of ATP-responses at recombinant P2X2 receptors and its dependence
      on extracellular pH.
AB  - 1. Using recombinant P2X2 receptors expressed in Xenopus oocytes, the modulatory
      effects of zinc (Zn2+) on ATP-responses were studied under voltage-clamp
      conditions and at different levels of extracellular pH. 2. Zn2+ (0.3-300 microM)
      added to the bathing medium potentiated ATP-activated membrane currents,
      increasing ATP-responses by up to 20 fold. This potentiating effect was reversed
      on washout. Zn2+-potentiation was reduced in an exponential manner (decaying 1/e
      in 42 s) as the interval was lengthened between adding Zn2+ then ATP to the
      superfusate. 3. The potentiating effect of Zn2+ was progressively diminished by
      acidic shifts in extracellular pH (pHe) which, of itself, also potentiated ATP
      responses at P2X2 receptors. The maximal potentiating effects of Zn2+ and H+ were
      not additive. 4. Neither Zn2+ nor H+ potentiation of ATP-responses was abolished
      by diethylpyrocarbonate (DEPC, 0.3-3 mM), which irreversibly denatures histidyl
      residues. Nine histidyl residues are present in the extracellular loop of P2X2
      receptors. 5. Zn2+ also enhanced the blocking activity of the P2 receptor
      antagonist suramin at P2X2 receptors. Therefore, Zn2+ also mimics H+ in
      increasing suramin-activity at P2X2 receptors. 6. In summary, Zn2+ and H+
      potentiate agonist and antagonist activity at P2X2 receptors but their effects
      are not wholly alike for receptor agonism. There, the potentiating effects of
      Zn2+ are time-dependent and gradually convert to inhibition while those of H+ are
      time-independent, persistent and more potent, suggesting that either these
      modulators interact in a different way with a single allosteric site or with
      different allosteric sites.

PMID- 9559906
TI  - Characterization of prejunctional 5-HT1 receptors that mediate the inhibition of
      pressor effects elicited by sympathetic stimulation in the pithed rat.
AB  - 1. A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor
      responses induced in vivo by electrical stimulation of the sympathetic outflow
      from the spinal cord of pithed rats. All animals had been pretreated with
      atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequency
      dependent increases in blood pressure. Intravenous infusion of 5-CT at doses of
      0.01, 0.1 and 1 mg kg(-1) min(-1) reduced the pressor effects obtained by
      electrical stimulation. The inhibitory effect of 5-CT was significantly more
      pronounced at lower frequencies of stimulation. In the present study we
      characterized the pharmacological profile of the receptors mediating the above
      inhibitory effect of 5-CT. 2. The inhibition induced by 0.01 microg kg(-1) min(
      1) of 5-CT on sympathetically-induced pressor responses was partially blocked
      after i.v. treatment with methiothepin (10 microg kg(-1)), WAY-100,635 (100
      microg kg(-1)) or GR127935T (250 microg kg(-1)), but was not affected by
      cyanopindolol (100 microg kg(-1)). 3. The selective 5-HT1A receptor agonist 8-OH
      DPAT and the selective 5-HT(1B/1D) receptor agonists sumatriptan and L-694,247
      inhibited the pressor response, whereas the 5-HT1B receptor agonists CGS-12066B
      and CP-93,129 and the 5-HT2C receptor agonist m-CPP did not modify the pressor
      sympathetic responses. 4. The selective 5-HT1A receptor antagonist WAY-100,635
      (100 microg kg(-1)) blocked the inhibition induced by 8-OH-DPAT and the selective
      5-HT(1B/1D) receptor antagonist GR127935T (250 microg kg(-1)) abolished the
      inhibition induced either by L-694,247 or sumatriptan. 5. None of the 5-HT
      receptor agonists used in our experiments modified the pressor responses induced
      by exogenous noradrenaline (NA). 6. These results suggest that the presynaptic
      inhibitory action of 5-CT on the electrically-induced pressor response is
      mediated by both r-5-HT1D and 5-HT1A receptors.

PMID- 9559908
TI  - Nitric oxide-related cyclic GMP-independent relaxing effect of N-acetylcysteine
      in lipopolysaccharide-treated rat aorta.
AB  - 1. We have recently demonstrated the formation of protein-bound dinitrosyl-iron
      complexes (DNIC) in rat aortic rings exposed to lipopolysaccharide (LPS) and
      shown that N-acetylcysteine (NAC) can promote vasorelaxation in these arteries,
      possibly via the release of nitric oxide (NO) as low molecular weight DNIC from
      these storage sites. The aim of the present study was to investigate further the
      mechanism of the relaxation induced by NAC in LPS-treated vessels. 2. In rings
      incubated with LPS (10 microg ml(-1) for 18 h) and precontracted with
      noradrenaline (NA, 3 microM) plus N(omega)-nitro-L-arginine methylester (L-NAME,
      3 mM), the relaxation evoked by NAC (0.1 to 10 mM) was abolished by 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM, a selective inhibitor of
      soluble guanylyl cyclase) but not affected by Rp-8-bromoguanosine 3'5'-cyclic
      monophosphorothioate (Rp-8BrcGMPS, 60 microM a selective inhibitor of cyclic GMP
      dependent protein kinase). Tetrabutylammonium (TBA, 3 mM, as a non selective K+
      channels blocker) or elevated concentration of external KCl (25 or 50 mM)
      significantly attenuated the NAC-induced relaxation. Selective K+ channels
      blockers (10 microM glibenclamide, 0.1 microM charybdotoxin, 0.5 microM apamin or
      3 mM 4-aminopyridine) did not affect the NAC-induced relaxation. The relaxing
      effect of NAC (10 mM) was not associated with an elevation of guanosine 3':5'
      cyclic monophosphate (cyclic GMP) in LPS-treated rings. 3. In aortic rings
      precontracted with NA (0.1 microM), low molecular weight DNIC (with thiosulphate
      as ligand, 1 nM to 10 microM) evoked a concentration-dependent relaxation which
      was antagonized by ODQ (1 microM) and Rp-8BrcGMPS (150 microM) but not
      significantly affected by TBA (3 mM) or by the use of KCl (50 mM) as
      preconstricting agent. The relaxation produced by DNIC (0.1 microM) was
      associated with an 11 fold increase in aortic cyclic GMP content, which was
      completely abolished by ODQ (1 microM). 4. Taken together with our previous data,
      the main finding of the present study is that the vascular relaxation induced by
      NAC in LPS-treated aorta, although probably related to NO through an interaction
      via preformed NO stores, was not mediated by activation of the cyclic GMP
      pathway. It may involve the activation of TBA-sensitive K+ channels. The
      differences in the mechanism of relaxation induced by NAC and by exogenous DNIC
      suggest that the generation of low molecular weight DNIC from protein-bound
      species does not play a major role in the NAC-induced relaxation observed in LPS
      treated rat aorta. In addition, it is suggested that ODQ may display other
      properties than the inhibition of soluble guanylyl cyclase.

PMID- 9559909
TI  - Cholecystokinin-8 regulation of NGF concentrations in adult mouse brain through a
      mechanism involving CCK(A) and CCK(B) receptors.
AB  - 1. Nerve growth factor (NGF), a powerful agent for the growth, differentiation
      and regeneration of lesioned cells of the central and peripheral nervous systems,
      has in recent years been indicated as a potential therapeutic agent capable of
      reversing the processes of cell damage in neurodegenerative events in man. Since
      NGF does not cross the blood-brain barrier and central NGF administration
      requires invasive surgical procedures, the discovery of substances modulating in
      vivo NGF synthesis in the brain will be extremely useful for a possible clinical
      use of NGF. 2. The aim of the present study to analyse if the content of NGF in
      the brain of adult mice can be affected by peripheral administration of
      cholecystokinin-8 (CCK-8), a well known neuropeptide which has stimulant actions
      on neurons in the brain and promotes a variety of neurobehavioural effects both
      in man and rodents. 3. The dose-response and time course effects of an i.p.
      injection of CCK-8 on the NGF concentrations in the hippocampus, cortex,
      hypothalamus and pituitary of adult male mice were analysed by use of a sensitive
      immunoenzymatic assay for NGF. The effects of pretreatment with selective CCK(A)
      and CCK(B) receptor antagonists and atropine on the NGF response to CCK injection
      were also studied. 4. The effects of CCK-8 were dose- and time-dependent and the
      injection of 8 nmol kg(-1) resulted in a 3 fold increase of NGF levels in the
      hypothalamus and pituitary, and about a 60% increase in the hippocampus. No
      effects were observed in the cortex. Pretreatment with a selective CCK(A)
      receptor antagonist blocked the CCK-induced NGF increase in the hypothalamus and
      pituitary. In the hippocampus the same effect was obtained with a CCK(B) receptor
      antagonist. Pretreatment with atropine suppressed the CCK-induced effects on NGF
      levels in all the brain regions examined. 5. Our results showing that i.p.
      injection with CCK-8 can modulate NGF levels in the brain through a mechanism
      which seems, in part, to be mediated via the vagal afferents, indicate that this
      neuropeptide may represent a useful pharmacological approach to enhance
      endogenous NGF levels in neuropathologies associated with a neurotrophin deficit.

PMID- 9559911
TI  - Prostaglandin E2 suppression of acetylcholine release from parasympathetic nerves
      innervating guinea-pig trachea by interacting with prostanoid receptors of the
      EP3-subtype.
AB  - 1. We have demonstrated recently that exogenous prostaglandin E2 (PGE2) inhibits
      electrical field stimulation (EFS)-induced acetylcholine (ACh) release from
      parasympathetic nerve terminals innervating guinea-pig trachea. In the present
      study, we have attempted to characterize the pre-junctional prostanoid
      receptor(s) responsible for the inhibitory action of PGE2 and to assess whether
      other prostanoids modulate, at a prejunctional level, cholinergic
      neurotransmission in guinea-pig trachea. To this end, we have investigated the
      effect of a range of both natural and synthetic prostanoid agonists and
      antagonists on EFS-evoked [3H]-ACh release. 2. In epithelium-denuded tracheal
      strips pretreated with indomethacin (10 microM), PGE2 (0.1 nM-1 microM) inhibited
      EFS-evoked [3H]-ACh release in a concentration-dependent manner with an EC50 and
      maximal effect of 7.62 nM and 74% inhibition, respectively. Cicaprost, an IP
      receptor agonist, PGF2alpha and the stable thromboxane mimetic, U46619 (each at 1
      microM), also inhibited [3H]-ACh release by 48%, 41% and 35%, respectively. PGD2
      (1 microM) had no significant effect on [3H]-ACh release. 3. The selective TP
      receptor antagonist, ICI 192,605 (0.1 microM), completely reversed the inhibition
      of cholinergic neurotransmission induced by U-46619, but had no significant
      effect on similar responses effected by PGE2 and PGF2alpha. 4. A number of EP
      receptor agonists mimicked the ability of PGE2 to inhibit [3H]-ACh release with a
      rank order of potency: GR63799X (EP3-selective) > PGE2 > M&B 28,767 (EP3
      selective) > 17-phenyl-omega-trinor PGE2 (EP1-selective). The EP2-selective
      agonist, AH 13205 (1 microM), did not affect EFS-induced [3H]-ACh release. 5.
      AH6809 (10 microM), at a concentration 10 to 100 times greater than its pA2 at DP
      , EP1- and EP2-receptors, failed to reverse the inhibitory effect of PGE2 or 17
      phenyl-omega-trinor PGE2 on [3H]-ACh release. 6. These results suggest that PGE2
      inhibits [3H]-ACh release from parasympathetic nerves supplying guinea-pig
      trachea via an interaction with prejunctional prostanoid receptors of the EP3
      receptor subtype. Evidence for inhibitory prejunctional TP- and, possibly, IP
      receptors was also obtained although these receptors may play only a minor role
      in suppressing [3H]-ACh release when compared to receptors of the EP3-subtype.
      However, the relative importance of the different receptors will depend not only
      on the sensitivity of guinea-pig trachea to prostanoids but on the nature of the
      endogenous ligands released locally that have activity on parasympathetic nerves.

PMID- 9559910
TI  - The expression of functional postsynaptic alpha2-adrenoceptors in the corpus
      cavernosum smooth muscle.
AB  - 1. The purpose of this study was to determine if corpus cavernosum smooth muscle
      expresses functional postsynaptic alpha2-adrenoceptors (AR). 2. The alpha2
      adrenoceptor agonist UK 14,304 elicited concentration-dependent contractions in
      rabbit corpus cavernosum smooth muscle (CCSM). The half-maximal response occurred
      at 0.32+/-0.03 microM and the maximum contraction at 10 microM UK 14,304. 3.
      Pretreatment of CCSM strips with selective alpha2-adrenoceptor antagonists,
      rauwolscine and RS-15385, produced rightward shifts in the dose-response curves
      to UK 14,304 (pA2 values 7.1 and 8.5, respectively). In contrast, these
      antagonists did not alter contraction induced by the alpha1-adrenoceptor agonist
      phenylephrine (PE) or oxymetazoline. UK 14,304-induced contractions were also
      inhibited by prazosin (pA2 = 9.08). 4. UK 14,304-induced contractions, unlike
      those to PE, were highly dependent on the presence of extracellular Ca2+. 5. [3H]
      rauwolscine bound to CCSM membranes with high affinity (Kd = 1.5 nM). [3H]
      rauwolscine binding was displaced by unlabelled rauwolscine, RS-15385, UK 14,304
      and prazosin, but not by PE. 6. UK 14,304 inhibited forskolin and prostaglandin
      E1 (PGE1)-induced increases in intracellular cyclic AMP concentration in primary
      cultures of rabbit CCSM cells. 7. These results demonstrate that CCSM expresses
      Gi-coupled postsynaptic alpha2-adrenoceptors, and activation of these receptors
      causes contraction of trabecular smooth muscle.

PMID- 9559912
TI  - SB-205384: a GABA(A) receptor modulator with novel mechanism of action that shows
      subunit selectivity.
AB  - 1. SB-205384, and its (+) enantiomer (+)-SB-205384 were tested for their
      modulatory effects on human GABA(A) receptor subunit combinations expressed in
      Xenopus oocytes by electrophysiological methods. 2. The slowing of the decay rate
      induced by SB-205384 on native GABA-activated currents in rat neurones was also
      seen on GABA(A) currents in oocytes expressing human GABA(A) subunits. This
      temporal effect was observed for the alpha3beta2gamma2 subunit combination with
      little effect in subunit combinations containing either alpha1 or alpha2. 3.
      Potentiation of the peak amplitude of the GABA-activated currents by SB-205384 or
      (+)-SB-205384 was less specific for a particular subunit combination, although
      the greatest effect at 10 microM drug was seen on the alpha3beta2gamma2 subunit
      combination. 4. In contrast, zolpidem, a benzodiazepine site modulator, did not
      significantly slow decay rates of GABA(A) currents in oocytes expressing the
      alpha3beta2gamma2 subunit combination. Zolpidem, as expected, did selectively
      potentiate GABA-activated currents on oocytes expressing the gamma2 subunit
      compared to those containing the gamma1. 5. The results show that the novel
      kinetic modulatory profile of SB-205384 is selective for the alpha3beta2gamma2
      subunit combination. This suggests that the compound is binding to a novel
      regulatory site on the subunit complex.

PMID- 9559914
TI  - Role of serine esterases in mast cell activation.
AB  - 1. A variety of chymotryptic substrates and inhibitors prevented the release of
      histamine and prostaglandin D2 from rat peritoneal mast cells stimulated with
      anti-IgE but not the calcium ionophore A23187 or a variety of polyamines. 2. The
      activity of the compounds was strikingly increased in cells reversibly
      permeabilized with ATP, indicating the importance of their effective
      incorporation into the cytosol. 3. The compounds produced a comparable inhibition
      of immunological, but not pharmacological, histamine release from human mast
      cells and basophils. 4. Treatment of rat mast cells with anti-IgE led to a marked
      increase in the total chymotryptic activity expressed by the cells. 5.
      Immunological, but not pharmacological, stimulation of permeabilized rat mast
      cells loaded with a fluorescent chymotryptic substrate led to a pronounced and
      rapid increase in fluorescence, indicating activation of the enzyme and
      hydrolysis of the substrate. These changes were attenuated by chymotryptic
      inhibitors. 6. In total, these data provide compelling evidence for the direct
      involvement of a serine protease in IgE-mediated histamine release from mast
      cells.

PMID- 9559913
TI  - Effect of PDE4 inhibitors on zymosan-induced IL-8 release from human neutrophils:
      synergism with prostanoids and salbutamol.
AB  - 1. The activation of neutrophils with particulate stimuli such as zymosan induces
      the generation of the C-X-C chemokine interleukin (IL)-8. There is evidence that
      neutrophil derived IL-8 plays an important role in human diseases such as the
      adult respiratory distress syndrome. In the present study, we examined the
      effects of cyclic AMP elevating agents on the ability of human neutrophils to
      generate IL-8 in response to zymosan particles. 2. The PDE4 inhibitor rolipram
      had limited effect on zymosan-induced IL-8 generation. In contrast, the PDE4
      inhibitors RP 73401 and SB 207499 concentration-dependently suppressed IL-8
      generation. The potency of these inhibitors was RP 73401 > SB 207499 > rolipram
      which is correlated with their rank order of potency at inhibiting the catalytic
      site of purified neutrophil PDE4. Pretreatment of neutrophils with the PDE3
      inhibitor ORG 9935 or the PDE5 inhibitor zaprinast had no effect on IL-8
      generation. 3. The prostanoids prostaglandin E1 (PGE1) and PGE2 inhibited zymosan
      induced IL-8 release from neutrophils in a dose-dependent manner, in response to
      10(-5) M PGE1 and PGE2 inhibiting IL-8 generation by 89% and 75%, respectively.
      Similarly, the beta2-adrenoceptor agonist salbutamol also inhibited IL-8
      generation, but it was less effective than the prostanoids. 4. Significant
      synergism between prostanoids or salbutamol and the PDE4 inhibitors to inhibit IL
      8 generation was observed. In contrast, there was no significant synergism
      between PGE2 and the PDE3 inhibitor ORG 9935 or the PDE5 inhibitor zaprinast. 5.
      In order to evaluate the potential role of protein kinase A in mediating the
      inhibitory effects of cyclic AMP-elevating agents, we used the protein kinase A
      inhibitors, H 89 and KT 5720. Pretreatment of neutrophils with these drugs
      completely reversed the inhibitory effects of a combination treatment with
      rolipram and PGE2 on zymosan-induced IL-8 release. 6. Microscopic examination
      revealed that most neutrophils contained one or more zymosan particles and that
      combination treatment with rolipram and PGE2 noticeably reduced the number of
      ingested particles. Moreover, there was a significant reduction in the percentage
      of neutrophils which ingested three or more zymosan particles. 7. Thus, our
      results demonstrate that cyclic AMP-elevating agents modulate the ability of
      neutrophils to generate IL-8 in response to a particulate stimulus. However,
      these agents also modulate the ability of neutrophils to phagocytose zymosan
      particles. Whether this effect will translate into inhibition of the ability of
      neutrophils to deal with infectious agents needs to be investigated further.

PMID- 9559915
TI  - Comparison of anaesthetic and non-anaesthetic effects on depolarization-evoked
      glutamate and GABA release from mouse cerebrocortical slices.
AB  - 1. Investigation with substances that are similar in structure, but different in
      anaesthetic properties, may lead to further understanding of the mechanisms of
      general anaesthesia. 2. We have studied the effects of two cyclobutane
      derivatives, the anaesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F3), and the
      non-anaesthetic, 1,2-dichlorohexafluorocyclobutane (F6), on K+-evoked glutamate
      and gamma-aminobutyric acid (GABA) release from isolated, superfused,
      cerebrocortical slices from mice, by use of h.p.l.c. with fluorescence detection
      for quantitative analysis. 3. At clinically relevant concentrations, the
      anaesthetic, F3, inhibited 40 mM K+-evoked glutamate and GABA release by 72% and
      47%, respectively, whereas the structurally similar non-anaesthetic, F6,
      suppressed evoked glutamate release by 70% but had no significant effects on
      evoked GABA release. A second exposure to 40 mM KCl after a approximately 30 min
      washout of F3 or F6 showed recovery of K+-evoked release, suggesting that F3 and
      F6 did not cause any non-specific or irreversible changes in the brain slices. 4.
      Our findings suggest that suppression of excitatory neurotransmitter release may
      not be directly relevant to the primary action of general anaesthetics. A
      mechanism involving inhibitory postsynaptic action is implicated, in which a
      moderate suppression of depolarization-evoked GABA release by the anaesthetic may
      be consistent with the enhancement of postsynaptic GABAergic activities.

PMID- 9559916
TI  - Neurogenic and non-neurogenic responses in the urinary bladder of hibernating
      hamster.
AB  - 1. Purinergic and cholinergic components of parasympathetic neurotransmission and
      contractile responses to exogenous alpha,beta-methylene ATP, acetylcholine,
      substance K, substance P, calcitonin gene-related peptide, vasoactive intestinal
      polypeptide and capsaicin have been investigated in the urinary bladder of
      hibernating hamsters (4 weeks), cold exposed (4 weeks) and age-matched controls.
      2. Electrical field stimulation (EFS) evoked increased frequency-dependent
      contractions in the detrusor strips from hibernating hamsters compared with those
      obtained from cold-exposed and age-matched animals. Tetrodotoxin (10(-6) M)
      completely blocked the frequency-dependent contractions in all groups. 3. The
      purinergic component of the parasympathetic neurotransmission was not affected in
      hibernating and cold-exposed animals while the cholinergic component was
      increased with respect to age-matched animals. The neurogenic response to EFS,
      still present after incubation with atropine (10(-6) M) and suramin (10(-4) M),
      was attenuated by indomethacin (10(-6) M) and blocked by tetrodotoxin (10(-6) M).
      4. Exogenous administration of alpha,beta-methylene ATP elicited a significantly
      reduced contraction in strips from hibernating and cold-exposed hamsters relative
      to age-matched animals. The contractile response to exogenous acetylcholine was
      greater in the detrusors from hibernating hamsters than in cold-exposed and age
      matched animals. Substance K elicited reduced contractions in preparations from
      hibernating animals compared with cold-exposed and control animals. Calcitonin
      gene-related peptide, vasoactive intestinal polypeptide, substance P and
      capsaicin did not elicit any relaxant or contractile response either at resting
      tone or in carbachol (5 x 10(-7) M)-precontracted tissues. 5. In summary, our
      findings indicate that 4 weeks of hibernation can significantly increase
      neurogenic responses in the hamster urinary bladder. This appears to be due to an
      increase in postjunctional responses to acetylcholine. In contrast, there was a
      decrease of the postjunctional responses to the parasympathetic cotransmitter ATP
      and also to the sensory-motor neurotransmitter substance K.

PMID- 9559917
TI  - Active sleep-related depolarization of feline trigemino-thalamic afferent
      terminals.
AB  - Presynaptic depolarization of trigemino-thalamic (TGT) terminals may contribute
      to modulation of ascending oro-facial somatosensory information during active (or
      rapid eye movement) sleep. The relative excitability of TGT terminals was
      inferred from changes in the current required to maintain an antidromic firing
      probability of 50% (EC50) during quiet wakefulness as compared to active sleep.
      Depolarization or hyperpolarization of TGT terminals was defined as a decrease or
      increase, respectively, in the EC50. Overall, the EC50 of 8 TGT terminals was
      reduced by a mean 8.8+/-3.6 microA during active sleep relative to quiet
      wakefulness. This result suggests that depolarization of TGT terminals, which may
      act to suppress the transfer of sensory information from the trigeminal nucleus
      to the thalamus, occurs during active sleep.

PMID- 9559918
TI  - Nitric oxide synthase activity in the dorsal periaqueductal gray of rats
      expressing innate fear responses.
AB  - Immunohistochemical studies have shown nitric oxide synthase (NOS)-positive
      neurons in the dorsolateral sector of periaqueductal gray (PAG), a neural site
      known to be critical for the expression of defensive responses. In the present
      study, we first characterized the dorsal PAG (dPAG) NOS, and then examined NOS
      activity and cyclic GMP (cGMP) accumulation in the dPAG of rats exposed to a
      predator (cat) for 15 min. NOS activity evaluated by enzymatic conversion of
      [3H]arginine to [3H]citrulline in dPAG of exposed rats increased 14.6% and the
      cGMP radioimmunoassay showed an increase of 30.6% in relation to non-exposed
      rats. These results suggest an involvement of the NO/cGMP pathway in the dPAG
      during defensive responses.

PMID- 9559919
TI  - Does glutamate mediate brain damage in acute encephalitis?
AB  - Cerebrospinal fluid (CSF) amino acid neurotransmitter concentrations in 23
      patients with acute encephalitis were compared with those in patients with acute
      brain infarction, multiple sclerosis and controls. The concentration of glutamate
      was significantly higher in encephalitis (5.2+/-6.7 micromol/l) and stroke
      patients (9.6+/-14.2 micromol/l) than in MS patients (1.6+/-0.9 micromol/l) and
      controls (1.7+/-0.8 micromol/l; p < 0.001). The concentration of glycine was
      significantly higher in encephalitis (11.0+/-4.7 micromol/l) than in stroke
      (7.6+/-3.2 micromol/l) and MS patients (6.3+/-2.1 micromol/l) or controls (5.6+/
      1.8 micromol/l; p < 0.002). Taurine levels were significantly lower in
      encephalitis patients than in the other groups (p = 0.04). The correlation of
      high glutamate levels with poor outcome was almost significant (Kendall tau 0.63,
      p = 0.06). Our observations suggest that exicitotoxic neurotransmission may play
      an important role in the series of events that lead to neuronal damage in
      encephalitis.

PMID- 9559920
TI  - Activation of inwardly rectifying K+ channels by GABA-B receptors expressed in
      Xenopus oocytes.
AB  - In Xenopus oocytes coinjected with poly(A)+ RNA derived from the rat cerebellum
      and cRNAs for the cloned G protein-gated inwardly rectifying K+ channel (GIRK),
      GIRK1 and GIRK2, the GABA-B agonist baclofen elicited inwardly rectifying K+
      currents. The inward K+ currents elicited by baclofen were inhibited by the
      selective GABA-B antagonists 2-OH saclofen and CGP 35348, and by the GIRK
      inhibitor Ba2+. In contrast, baclofen caused no currents in oocytes injected with
      the cerebellar poly(A)+ RNA alone, the poly(A)+ RNA and cRNA for GIRK1 or GIRK2,
      or only cRNAs for GIRK1 and GIRK2. These findings indicate that GABA-B receptors
      in the rat cerebellum were functionally expressed in Xenopus oocytes and
      activated the cloned GIRKs composed of GIRK1 and GIRK2 as heteromultimers.

PMID- 9559921
TI  - Nitric oxide contributes to central sensitization following intradermal injection
      of capsaicin.
AB  - This study provides direct evidence from measurements of its metabolites, NO2-
      and NO3-, that NO is released in the spinal cord during central sensitization. A
      microdialysis fiber was implanted in the dorsal horn at L5 for collecting
      dialysate and administering drugs. Dialysate was pumped through a cadminum
      reducing column, a post-column derivatizing unit, and then a u.v. detector. After
      injection of capsaicin into one hind foot, NO2-increased in the dialysate.
      Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) significantly reduced
      NO release induced by a second injection of capsaicin into the opposite foot.
      This supports the ideas that NO is involved in central sensitization in the
      spinal cord and contributes to hyperalgesia and allodynia following capsaicin
      injection.

PMID- 9559922
TI  - Estradiol upregulates Bcl-2 expression in adult brain neurons.
AB  - Bcl-2, a protein which negatively modulates apoptosis, is up-regulated by
      estrogen in several tissues. To determine the effect of estradiol on Bcl-2 in the
      adult brain, its immunoreactive distribution was examined in the hypothalamic
      arcuate nucleus of female rats under different endocrine conditions. The number
      of Bcl-2-immunoreactive neurons was significantly increased (p < 0.001) on the
      day of estrus compared with proestrus, diestrus and metestrus, was decreased by
      ovariectomy and showed a dose-response increase after estradiol administration to
      ovariectomized rats. Progesterone, when injected simultaneously with estradiol,
      reduced the effect of estradiol. These findings indicate that ovarian hormones
      regulate Bcl-2 in hypothalamic neurons and suggest that this protein may be
      involved in the neuroprotective effects of estrogen.

PMID- 9559923
TI  - Direct detection of uncaged glutamate and the laser photostimulation of cultured
      rat cortex.
AB  - The photostimulation of nerve cells using a caged compound is very useful because
      it is non-invasive and non-destructive compared with standard
      electrophysiological techniques. There are no methods, however, for continuously
      measuring the photo-uncaged 'free' compound concentration at high temporal and
      spatial resolutions which can detect how much uncaged compound has been applied
      to cells. Here, we used an electrochemical detection method for the real-time
      measurement of photo-uncaged glutamate. In this way, we were able to determine
      the amount of uncaged glutamate and investigate neural activities by tracing
      [Ca]i while simultaneously employing photostimulation and on-line glutamate
      measurement. The combination of an on-line sensor and laser-photostimulation with
      [Ca]i measurement could be a powerful tool with which to investigate synaptic
      connections and activities.

PMID- 9559924
TI  - Somatotopy of the human arm using fMRI.
AB  - We describe a technique for mapping out human somatosensory cortex using
      functional magnetic resonance imaging (fMRI). To produce cortical activation, a
      pneumatic apparatus presented subjects with a periodic series of air puffs in
      which a sliding window of five locations moved along the ventral surface of the
      left arm in a proximal-to-distal or distal-to-proximal direction. This approach,
      in which the phase-delay of the stimulus can be used to produce somatotopic maps
      of somatosensory cortex, is based on a method used to generate retinotopic maps
      of visual cortex. Functional images were acquired using an echoplanar 1.5T
      scanner and a T2*-weighted spiral acquisition pulse sequence. The periodic series
      of air puffs created phase-related activation in two cortical regions of the
      contralateral parietal lobe, the posterior bank of the central sulcus and a more
      posterior and lateral region.

PMID- 9559925
TI  - Selective activation of human cortical area V5A by a rotating visual stimulus in
      fMRI; implication of attentional mechanisms.
AB  - The human homologue of area V5A of rotation-selective cells in the monkey medial
      superior temporal area (MST) was identified using functional magnetic resonance
      imaging (fMRI). It was located within the border region of occipito-temporo
      parietal cortex, in four of 10 subjects on both sides, and on the right or left
      side in three subjects each. The stimulus was a black-and-white sine-modulated
      windmill presented either stationary or in rotation phases of 1 s duration. Areas
      V1-V3 did not show up with this paradigm. Focusing attention by mentally counting
      the number of rotation phases ensured high signal intensity in V5A, whereas
      moving attention away by counting electric stimuli to the wrist diminished it
      despite persistent fixation of gaze to the centre of the windmill.

PMID- 9559926
TI  - Endogenous apolipoprotein E suppresses LPS-stimulated microglial nitric oxide
      production.
AB  - The human apolipoprotein (apo) E4 isoform is associated with an increased risk
      for Alzheimer's disease (AD) and poor prognosis after acute CNS injury. Addition
      of human apoE inhibits murine microglial activation in culture, suggesting that
      microglia might be an important physiological target of apoE. In the present
      study, we examined the role of endogenous murine apoE in modulating microglial
      nitric oxide (NO) production following lipopolysaccharide (LPS) stimulation.
      Brain cultures from apoE-deficient mouse pups showed enhanced NO production
      relative to cultures from wild-type mice and from transgenic mice expressing the
      human apoE3 isoform, demonstrating that endogenous apoE produced by glial
      cultures is capable of inhibiting microglial function. ApoE produced within the
      brain may suppress microglial reactivity and thus alter the CNS response to acute
      and chronic injury.

PMID- 9559927
TI  - The uterine environment enhances cognitive competence.
AB  - Genetically identical mouse embryos were transferred into same-strain uteri
      (transfer controls) or into hybrid uteri. A third group was not transferred. When
      adult, the mice were given a series of behavioral tests. In-strain transfer
      controls differed from non-transfer mice only on two activity measures, and did
      not differ on any cognitive variable. In contrast, mice reared in hybrid uteri
      were found to be superior to in-strain transfer mice on discrimination learning,
      Lashley maze learning and Morris maze learning; they also showed better
      adaptation in an avoidance learning shuttlebox. To our knowledge this is the
      first study showing that the uterine environment can have a general enhancing
      effect upon cognitive competence across a broad range of behaviors.

PMID- 9559928
TI  - [K+]out accelerates inactivation of Shal-channels responsible for A-current in
      rat CA1 neurons.
AB  - Somato-dendritic subthreshold transient potassium current [I(SA)] was measured in
      acutely isolated rat hippocampal CA1 pyramidal neurons. The inactivation of this
      current was insensitive to externally applied H2O2 (20 mM) which causes cysteine
      oxidation. This result suggests that Shal-channels not Shaker Kv1.4 channels
      underlie the somato-dendritic I(SA) in rat CA1 pyramidal neurons. The kinetics of
      the I(SA) inactivation was measured at various [K+]out. Increase in [K+]out leads
      to acceleration of Shal-channel inactivation. Thus, the shift in [K+]out from 1
      to 50 mM results in decreased inactivation time constant from 37 to 19 ms. This
      effect of [K+]out on the I(SA) is opposite to the previously described action of
      [K+]out on the inactivation of Shaker K+ channels.

PMID- 9559929
TI  - Attenuation of nociceptin/orphanin FQ-induced signaling by N-methyl-D-aspartate
      in neuronal cells.
AB  - Acute incubation of NMDA with neuroblastoma x glioma hybrid (NG108-15) cells or
      neuroblastoma SK-N-SH cells produced significant attenuation of
      nociceptin/orphanin FQ (N/OFQ)-induced activation of G protein and inhibition of
      adenylyl cyclase. The attenuation of N/OFQ signaling by NMDA was dose-dependent,
      blockable by NMDA antagonists, and not observed in cells lacking NMDA receptors,
      indicating that the effect of NMDA is mediated by the NMDA receptor. Furthermore,
      NMDA antagonist pretreatment greatly attenuated N/OFQ-induced acute homologous
      desensitization of ORL1. Interestingly, the signaling induced by etorphine, an
      opioid agonist of wide spectrum, was sensitive to NMDA treatment in NG108-15 but
      insensitive in SK-N-SH cells, suggesting differential modulation of opioid
      signaling by NMDA. The attenuation effects of NMDA on mu opioid receptor-mediated
      signaling were also observed.

PMID- 9559930
TI  - MK-801 reinstates drug-seeking behaviour in cocaine-trained rats.
AB  - We evaluated the incentive motivational properties of MK-801 by determining its
      priming effect on drug-seeking behaviour following extinction of cocaine self
      administration, an animal model for drug craving. Rats were allowed to self
      administrate cocaine (0.5 mg/kg) or saline during 10 daily sessions. MK-801 (0.1
      0.25 mg/kg, i.p.) dose-dependently reinstated responding for cocaine following an
      extinction period of 3 weeks. Responding was selectively enhanced in the
      previously drug-paired hole and was completely absent in rats with a history of
      saline self-administration. These data provide evidence for a possible role of
      NMDA receptors in the incentive motivation underlying cocaine-seeking behaviour.
      In addition, the ability of MK-801 to elicit drug-seeking behaviour may prove to
      be a serious drawback for the proposed use of NMDA antagonists in the treatment
      of drug addiction.

PMID- 9559931
TI  - 5HT1B and 5HT1D receptor mRNA differential co-localization with peptide mRNA in
      the guinea pig trigeminal ganglion.
AB  - To investigate the possible role of 5HT1B and/or 5HT1D receptors in controlling
      neurogenic inflammation, we performed a co-localization study of the mRNA for
      5HT1B and 5HT1D receptors and of substance P or calcitonin gene-related peptide
      (CGRP) mRNA in the guinea pig trigeminal ganglion using double labelling in situ
      hybridization techniques. The 5HT1D receptor mRNA is abundant whereas 5HT1B
      receptor mRNA is scarce. The vast majority of cells containing substance P mRNA
      also contained 5HT1B receptor mRNA, but very few cells expressed substance P mRNA
      and 5HT1D receptor mRNA. Both receptor mRNAs were co-localized with CGRP mRNA.
      Hence, 5HT1D receptors may control the release of CGRP only, whereas 5HT1B
      receptors may control the release of both substance P and CGRP. The question
      remains whether selective 5HT1D agonists will have migraine abortive properties.

PMID- 9559932
TI  - Central antinociceptive effects of meloxicam on rat spinal cord in vitro.
AB  - Non-steroidal anti-inflammatory drugs inhibit constitutive (COX-1) and induced
      cyclooxygenase (COX-2), blocking prostaglandin production. We have compared the
      effects on nociceptive reflexes of meloxicam, which is COX-2 selective, with
      indomethacin, which is non-selective, using an in vitro spinal cord preparation.
      Cords were taken from naive rats, and from rats with carrageenan-induced
      hyperalgesia of one hindpaw. Reflex thresholds were lower in carrageenan
      preparations. Superfusion with meloxicam (10-100 microM) dose-dependently
      inhibited baseline reflexes and wind-up in normal and carrageenan preparations,
      whereas indomethacin (100-300 microM) had no effect. Thus meloxicam inhibits
      spinal reflexes, whereas indomethacin does not, despite its high affinity for
      both COX isoforms. We conclude that meloxicam has spinal antinociceptive actions
      which cannot be explained by the current concept of COX inhibition.

PMID- 9559933
TI  - Enhanced visual responses in cat dLGN--potentiation by priming with excitatory
      amino acids.
AB  - Sustained iontophoresis of NMDA potentiated visual responses for minutes after
      the application in 16 of 38 cells (42%), peaking 3 min after the end of the
      application and declining to control levels within 12 min. Potentiation was also
      seen after application of ACPD (36%, n = 14) and AMPA (29%, n = 14), but not
      after application of ACh (n = 20). ACh also excites dLGN cells, but does not
      interact with amino acid receptors, and ACh receptors are not directly involved
      in the transmission of visual information. We suggest that this modulation is a
      form of visually induced potentiation which permits dynamic modification of the
      strength of visual information to be relayed to the cortex depending upon the
      history of previous activity levels.

PMID- 9559934
TI  - Abeta-fiber mediated activation of cingulate cortex as correlate of central post
      stroke pain.
AB  - A patient is presented who suffered a lateral brainstem infarction which
      selectively abolished pain and temperature sensitivity in the lower right limb.
      One year later central post-stroke pain had developed in the affected limb with
      touch and cold allodynia. P40m dipoles calculated from magnetoencephalographic
      fields after electrical stimulation of both tibial nerves were localized in SI as
      is seen in normal subjects. However, stimulation of the affected side caused deep
      pain sensations and elicited a large N80m component, best explained by an
      additionally active dipole in cingulate cortex. This early co-activation in a
      limbic structure suggests peripheral Abeta-fiber mediation and lemniscal
      projection. Abnormal link to the pain system may be due to sensitization and
      reorganization above the level of nociceptive deafferentation.

PMID- 9559935
TI  - Actin cytoskeleton regulates ion channel activity in retinal neurons.
AB  - The actin cytoskeleton is an important contributor to the integrity of cellular
      shape and responses in neurons. However, the molecular mechanisms associated with
      functional interactions between the actin cytoskeleton and neuronal ion channels
      are largely unknown. Whole-cell and single channel recording techniques were thus
      applied to identified retinal bipolar neurons of the tiger salamander (Ambystoma
      tigrinum) to assess the role of acute changes in actin-based cytoskeleton
      dynamics in the regulation of voltage-gated ion channels. Disruption of
      endogenous actin filaments after brief treatment (20-30 min) with cytochalasin D
      (CD) activated voltage-gated K+ currents in bipolar cells, which were largely
      prevented by intracellular perfusion with the actin filament-stabilizer agent,
      phalloidin. Either CD treatment under cell-attached conditions or direct addition
      of actin to excised, inside-out patches of bipolar cells activated and/or
      increased single K+ channels. Thus, acute changes in actin-based cytoskeleton
      dynamics regulate voltage-gated ion channel activity in bipolar cells.

PMID- 9559936
TI  - Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars
      reticulata neurones by a cannabinoid agonist.
AB  - Whole-cell patch-clamp recordings were made from substantia nigra pars reticulata
      (SNR) neurones in rat midbrain slices to investigate the electrophysiological
      effects of cannabinoids. The cannabinoid receptor agonist WIN 55212-2 (10 microM)
      significantly reduced intranigrally evoked and spontaneous inhibitory post
      synaptic currents (IPSCs) which were mediated by GABA(A) receptors. The
      postsynaptic current induced by bath application of GABA was not affected by the
      presence of WIN 55212-2. The actions of WIN 55212-2 were not mimicked by the
      inactive enantiomer WIN 55212-3. WIN 55212-2 also hyperpolarized the membrane of
      SNR neurones in a tetrodotoxin/0-Ca2+-insensitive manner. These data suggest that
      cannabinoids modulate the activity of SNR neurones by presynaptic inhibition of
      GABA inputs. They may also exert a direct post-synaptic inhibition on these
      neurones.

PMID- 9559937
TI  - Anticonvulsant effects of intra-hippocampal injection of TRH in amygdala kindled
      rats.
AB  - The anticonvulsant effects of intra-hippocampal thyrotropin-release hormone (TRH)
      were examined in amygdala kindled rats. Subjects were implanted unilaterally with
      an electrode in the amygdala and bilaterally with guide cannulae in the
      hippocampus, aimed at the dorsal and ventral dentate gyri. Rats were kindled
      daily with suprathreshold electrical stimulation (800 microA, 1 ms pulse width,
      100 Hz, duration 0.5 s) until seizures were reliably elicited. The afterdischarge
      (AD) duration, seizure duration, and seizure stage were recorded daily, and AD
      thresholds were determined after kindling was completed. TRH was infused into
      each of the four cannulae of freely moving rats at doses of 0 (vehicle), 1.25,
      2.5 and 5 microg/site. Five minutes after the last infusion, the rats received
      electrical stimulation at their AD threshold (mean = 135 microA) + 50 microA. TRH
      reduced the AD and seizure duration in a dose-dependent manner. At the dose of
      2.5 microg/site, TRH also reduced AD and seizure duration in rats stimulated with
      suprathreshold current (800 microA). However, TRH had minimal effects on seizure
      stage irrespective of the stimulation intensity. These results suggest that the
      seizure-induced elevations of TRH in the hippocampus, as demonstrated in previous
      studies, may be part of an endogenous anticonvulsant compensatory mechanism and
      that further elevations of TRH in the hippocampus can produce anticonvulsant
      effects mainly by reducing the AD and seizure duration.

PMID- 9559938
TI  - Human chromosomal localization of a gene for inositol monophosphatase by
      fluorescence in situ hybridization.
AB  - Inhibition of the enzyme inositol monophosphatase (IMPase) (E.C. 3.1.3.25) has
      been linked to the therapeutic action of lithium in the treatment of manic
      depression (bipolar) disorder. Because of the link between bipolar and IMPase, we
      felt it would be of considerable importance to determine the human chromosomal
      localization of the IMPase gene. Fluorescence in situ hybridization analysis
      using a human cDNA clone, which included the 5'-UTR and the complete coding
      region, mapped the human IMPase gene to chromosome 8q21.2-21.3. No gene locus for
      manic-depressive disorder has yet been identified. Further studies on this IMPase
      gene, and other potential gene variants and mutations, should help to determine
      if specific subgroups of patients with manic-depressive disorder can be
      determined on a molecular basis, with regard to the IMPase gene.

PMID- 9559939
TI  - Nerve growth factor potentiates the oxidative necrosis of striatal cholinergic
      neurons.
AB  - We examined the effects of nerve growth factor (NGF) on free radical
      neurotoxicity in striatal cell cultures. Following exposure to 30 microM Fe2+ or
      1 mM L-buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine
      synthetase, striatal neurons underwent cell body swelling and then widespread
      death over the next 24 h. The degeneration was prevented by addition of 100
      microM trolox, an antioxidant. Addition of 100 ng/ml BDNF beginning 12 h before
      Fe2+ or BSO potentiated necrosis of most striatal neurons after exposure to 10
      microM Fe2+ or 1 mM BSO. In contrast, treatment with 100 ng/ml NGF selectively
      potentiated the oxidative degeneration of striatal cholinergic neurons. The
      present findings provide additional evidence that NGF, like other neurotrophins,
      can potentiate oxidative neuronal cell necrosis.

PMID- 9559940
TI  - Computer model of antiepileptic effects mediated by alterations in GABA(A)
      mediated inhibition.
AB  - Results from a computer model of a thalamic network predict that agents
      augmenting GABA(A)-mediated inhibition in the reticular thalamic (RE) nucleus
      will be antiepileptic or desynchronizing. This provides support for the
      hypothesis that antiepileptics like benzodiazepines may exert their effects
      through an isolated increase of inhibition in the RE nucleus. When
      desynchronized, the model thalamocortical neurons showed a decreased probability
      of firing a low threshold spike, a decreased secondary inhibitory postsynaptic
      potential and a higher frequency of oscillations. The transition to desynchrony
      was also accompanied by an increased frequency in the firing of the model RE
      neurons.

PMID- 9559941
TI  - Dp116, talin, vinculin and vimentin immunoreactivities following nerve
      transection.
AB  - The time course of the expression of Dp116, talin, vinculin and vimentin in rat
      sciatic nerve was investigated after experimental transection. Dp116 was still
      found at 5 days after experiment in some degenerating myelinated fibers of both
      proximal and distal stumps. The findings are consistent with the known
      preservation of electrical excitability of the distal nerve in the first days
      after injury. Some regenerating nerve fibers into the neuroma also expressed
      Dp116 at 25 and 40 days after nerve transection. Talin and vinculin markedly and
      diffusely immunostained the neuroma. Talin in the distal stump and vimentin in
      both proximal and distal stumps were found decreased during the time course of
      the experiment. Vinculin binding increased in the distal stump, due to a real
      overexpression or simply to a cross-reaction to degeneration products.

PMID- 9559942
TI  - Increased survival of dopaminergic neurons by rasagiline, a monoamine oxidase B
      inhibitor.
AB  - Both deprenyl and rasagiline (R(+)-N-propargyl-1-aminoindane mesylate), at a
      concentration of 1-10 microM, increased survival in vitro of rat E14
      mesencephalic dopaminergic neurons that had been primed with 10% serum for 12 h
      (p < 0.05). Rasagiline, but not deprenyl, also increased total neuronal (MAP2
      positive) survival (p < 0.05) Under serum-free conditions, rasagiline, but not
      deprenyl, retained its neuroprotective action on dopaminergic neurones. GABAergic
      neurons were not affected by either deprenyl or rasagiline. Clorgyline, an MAO-A
      inhibitor, did not exert any of these effects. The protective action of
      rasagiline on dopaminergic neurons, even under stringent serum-free conditions,
      is striking, and warrants further investigation for a role in the treatment of
      Parkinson's disease.

PMID- 9559943
TI  - Functional thrombin receptor PAR1 in primary cultures of human glioblastoma
      cells.
AB  - In this study we investigated primary cultures obtained from two glioblastomas
      surgically removed from a 64-year-old man and a 50-year-old woman, respectively.
      The presence of the tethered ligand thrombin receptor PAR1 (protease-activated
      receptor 1) in these cells was demonstrated at the level of receptor binding by
      using immunofluorescence studies with the monoclonal anti-PAR1 antibody Mab 31-2.
      Stimulation of human glioblastoma cells both with alpha-thrombin and the thrombin
      receptor activating peptide TRAP-6 resulted in a series of [Ca+]i spikes as shown
      by confocal laser fluorescence microscopy with fluo-3 as calcium sensitive
      fluorescence indicator. This effect was completely blocked with the thrombin
      receptor antagonist peptide T1. Our results demonstrate functional thrombin
      receptors (PAR1) in primary cultures of human glioblastomas for the first time.

PMID- 9559944
TI  - Functional imaging of mirror and inverse reading reveals separate coactivated
      networks for oculomotion and spatial transformations.
AB  - Echoplanar functional magnetic resonance imaging (fMRI) was used to localize the
      cortical areas involved in the analysis of spatially transformed letter strings.
      Significant increases of the blood oxygen level-dependent (BOLD) signal for
      transformed vs normal reading were observed in the superior parietal lobule
      (SPL), along the intraparietal sulcus (IPS), in the frontal eye fields (FEF), and
      in the latero-occipital area LO. The respective contributions of oculomotor and
      spatial transformation areas to this activation pattern were separated by means
      of a control condition involving the execution and suppression of eye movements.
      Areas activated in association with the control of eye movements included the
      superior parietal lobule and the frontal eye fields. The cooperation of different
      brain areas was analysed by correlating the time course of task-dependent BOLD
      signal changes in these areas. This correlation analysis revealed coactivation of
      occipitotemporal object recognition areas and a spatial transformation area in
      the intraparietal sulcus during the reading of transformed letter strings. We
      suggest that cortical systems that are coactivated during complex cognitive tasks
      can be differentiated by the correlation analysis of BOLD signal time courses in
      spatially separate brain areas.

PMID- 9559945
TI  - Spectral components of cytosolic [Ca2+] spiking in neurons.
AB  - We show here, by means of evolutionary spectral analysis and synthesis of
      cytosolic Ca2+ ([Ca2+]c) spiking observed at the single cell level using digital
      imaging fluorescence microscopy of fura-2-loaded mouse cerebellar granule cells
      in culture, that [Ca2+]c spiking can be resolved into evolutionary spectra of a
      characteristic set of frequencies. Non-delayed small spikes on top of sustained
      [Ca2+]c were synthesized by a main component frequency, 0.132+/-0.012 Hz, showing
      its maximal amplitude in phase with the start of depolarization (25 mM KCI)
      combined with caffeine (10 mM) application. Delayed complex responses of large
      [Ca2+]c spiking observed in cells from a different set of cultures were
      synthesized by a set of frequencies within the range 0.018-0.117 Hz. Differential
      frequency patterns are suggested as characteristics of the [Ca2+]c spiking
      responses of neurons under different conditions.

PMID- 9559946
TI  - Cytosolic hippocampal PKC and aging: correlation with discrimination performance.
AB  - Adult and aged mice were submitted to a discrimination task in a radial maze
      (regular trials), and then to probe trials requiring them to form relational
      representations. Three weeks later, animals were again tested for regular and
      probe trials. Following another interval of 3 weeks, individual hippocampal
      cytosolic calcium-dependent and -independent PKC activities were measured.
      Performance of aged animals was impaired on probe but not regular trials and aged
      mice had lower hippocampal cytosolic calcium-dependent and -independent PKC
      activities than adults. Performance on probe trials was specifically correlated
      with calcium-dependent PKC activity. This suggests a specific relationship
      between the ability to form relational representations and hippocampal cytosolic
      calcium-dependent PKC activity.

PMID- 9559947
TI  - In vivo antinociceptive activity of anti-rat mGluR1 and mGluR5 antibodies in
      rats.
AB  - To examine the specific roles of group I metabotropic glutamate receptors
      (mGluRs) in nociceptive processing, we examined the effects of intrathecal (i.t.)
      treatment with antibodies raised against the C-terminals of mGluR1 and mGluR5 in
      various rat pain models. The effects of anti-mGluR1 IgG and anti-mGluR5 IgG were
      assessed in a model of persistent pain induced by intrathecal administration of
      the mGluR1/5 agonist DHPG, as well as in models of heat pain (plantar test),
      chemical pain (formalin test) and neuropathic pain. DHPG-induced spontaneous
      nociceptive behaviours (SNB) were significantly attenuated by i.t. treatment with
      either anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (10 and 30 microg). Neither
      anti-mGluR1 IgG (30 microg) nor anti-mGluR5 IgG (30 microg) significantly
      increased response latencies to noxious heat in the plantar test, compared with
      anti-rat IgG (control IgG). Moreover, neither antibody (30 microg) significantly
      reduced formalin pain scores as compared to control IgG. However, i.t. treatment
      with anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (30 microg) significantly
      reduced cold hypersensitivity exhibited 8 days after constriction injury of the
      sciatic nerve, supporting the contention that group I mGluRs play a role in the
      development of neuropathic pain. Because these antibodies were effective against
      neuropathic pain, and not acute heat or chemical noxious stimuli, these results
      suggest that mGluRs are involved in nociceptive processing in chronic pain states
      rather than signaling acute noxious stimuli, and that DHPG-induced pain may be
      mediated by similar mechanisms as neuropathic pain.

PMID- 9559948
TI  - Down-regulated NPY receptor subtype-5 mRNA expression in genetically obese mouse
      brain.
AB  - Brain neuropeptide Y (NPY) subtype-5 (Y5 receptor) mRNA expression in lean (+/+)
      and obese (ob/ob) C57Bl/6 mice was examined using a non-radioactive in situ
      hybridization detection method. Significant decreases in Y5 receptor mRNA
      expression were found in the ventromedial, dorsomedial and arcuate hypothalamic
      nuclei, midline thalamic nuclei, piriform, cingulate and retrosplenial granular
      cortices of the obese mouse brain. There were minor changes in the amount of Y5
      receptor mRNA expression in the hippocampal formation and medial habenular
      nucleus. Results indicated that Y5 receptor mRNA expression is downregulated in
      hereditary obese (ob/ob) mice. This is possibly due to over-expression of
      hypothalamic NPY which occurs in this phenotype.

PMID- 9559949
TI  - Possible synaptic connections of expiratory neurons in the medulla of newborn rat
      in vitro.
AB  - To elucidate synaptic interactions between expiratory (Exp) and other respiratory
      neurons in the ventrolateral medulla of brain stem-spinal cord preparations from
      newborn rats, we analyzed postsynaptic potentials in Exp and a subclass of
      inspiratory (Insp) neurons using whole-cell recordings. About 72% of the Exp
      neurons (Exp-p-i) showed Cl--dependent synaptic inhibition during the Insp and
      pre/post-Insp phases, corresponding to the active phase of the Insp and pre
      inspiratory (Pre-I) neurons, respectively. The other 28% neurons (Exp-i) received
      Cl--dependent inhibition during the Insp phase only. Some Insp neurons showed
      reversed IPSPs during the active phase of Exp-p-i after Cl-loading. We suggest
      the existence of inhibitory connections from Pre-I and Insp to Exp and from Exp
      to Insp neurons. Basic synaptic connections among respiratory neurons similar to
      those in intact adult mammals may already exist in newborn rats.

PMID- 9559950
TI  - Non-frontal P3b-like activity evoked by the Wisconsin Card Sorting Test.
AB  - Event related potentials (ERP) were recorded from 29 electrode positions in 10
      normal subjects while they performed a simplified version of the Wisconsin Card
      Sorting Test (WCST). The design focused on ERP differences between early and late
      trials within each WCST series. Topographic and dipole analyses confirmed the
      reliability of two ERP signs: one conspicuous mid-parietal P3b wave and one
      asymmetrical frontal-temporal component. A three-dipole model accounted for these
      ERP signs with > 90% accuracy even in individual subjects, and suggests a sub
      second activation of temporal-parietal and medial temporal association areas
      during card sorting. The WCST-related P3b wave is proposed to reflect working
      memory operations such as template matching and template formation during card
      sorting.

PMID- 9559951
TI  - Neuroanatomical correlates of the assessment of facial attractiveness.
AB  - Frontal cortical damage can lead to changes in affective aspects of personality.
      However, the difficulty of dissociating such abnormalities from cognitive
      disorders has overshadowed most previous findings. Regional cerebral blood flow
      (rCBF) was measured with positron emission tomography (PET) while normal subjects
      were assessing facial attractiveness. Two left frontal regions showed a
      significant increase in rCBF while assessing facial attractiveness. The increased
      rCBF in the left anterior frontal cortex correlated with the overall percentage
      of assessments of a face as unattractive, while that in the left fronto-temporal
      junction correlated with the percentage of assessments of a face as attractive.
      These findings provide direct evidence that the left frontal regions are engaged
      in the assessment of facial attractiveness.

PMID- 9559952
TI  - Neuroprotection by dehydroepiandrosterone-sulfate: role of an NFkappaB-like
      factor.
AB  - Levels of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S)
      decline during aging and reach even lower levels in Alzheimer's disease (AD).
      Previously published effects of DHEA and DHEA-S on unchallenged neuronal survival
      led us to test them in an excitotoxicity paradigm. While DHEA-S protected
      hippocampal neurons against glutamate, little protection was observed with
      equivalent doses of DHEA itself. This differential neuroprotection was consistent
      with the ability of DHEA-S (but not DHEA) to elevate a kappaB-dependent
      transcription factor activity, a phenomenon we previously have connected with
      neuroprotection. Furthermore, suppression of kappaB DNA-binding by 'decoy'
      oligonucleotides blocked the neuroprotective activity of DHEA-S. These findings
      imply that age-related declines in the availability of DHEA-S could exacerbate
      neurotoxicity, and the data suggest that therapeutic gains may be obtained with
      pharmacological manipulation of kappaB-dependent transcription in neurons.

PMID- 9559953
TI  - The time course of brain activations during response inhibition: evidence from
      event-related potentials in a go/no go task.
AB  - The cortical organization of executive control was investigated using event
      related potentials (ERPs). ERPs were collected while subjects performed a go/no
      go task that required response inhibition. First, around 260 ms after stimulus
      onset, an effect of response inhibition on ERPs was observed over inferior
      prefrontal areas. Generators in these regions were confirmed by source analysis.
      Later, between 300-600 ms after stimulus onset, a left lateralized fronto-central
      ERP effect was found which differed in topography from a non-specific effect of
      task difficulty. Source analysis indicated that generators in anterior cingulate
      and left premotor areas also contributed to this effect. Orchestrated activation
      of prefrontal areas and the anterior cingulate subserves executive function
      whereas relatively late activity of the left premotor cortex is involved in motor
      control.

PMID- 9559954
TI  - Does the cortical representation of body parts follow both injury to the related
      sensory peripheral nerve and its regeneration?
AB  - A study was made of the borderline between the physiological representations of
      the digits (D2, D3 and D4) and sinus whiskers in the rat primary somatosensory
      cortex after a contralateral infraorbital nerve crush. Following the injury, the
      physiological representation of the digits of the contralateral forepaw extended
      posterolaterally, occupying the anterolateral part of the whisker region
      (posteromedial barrel subfield). The extended physiological representation of the
      digits, though somewhat shrunken, remained after the reappearance of whisker
      evoked responses, forming an overlapping area between the obligate digit and
      whisker representations. The findings emphasize the importance of afferent inputs
      in modulating cortical organization, but show that a reversible change in a
      sensory input (nerve damage) does not result in a perfectly reversible change in
      cortical representation.

PMID- 9559955
TI  - Calculating internal dose by convolution from SPECT/MR fusion images.
AB  - A new computer program was developed to calculate the absorbed dose. The program
      is based on the use of the convolution method and abdominal SPECT/MR fusion
      images. The applicability of the method was demonstrated by using data from
      (111)In-labeled thrombocyte and 99mTc-labeled colloid studies of three healthy
      volunteers. Dose distributions in the volunteers and the average absorbed doses
      in liver and spleen were calculated. The average doses for 99mTc-labeled colloid
      study were 0.07 +/- 0.02 (liver) and 0.046 +/- 0.005 mGy/MBq (spleen). The
      results are in good agreement with a Monte Carlo (MC) based method (0.074 for
      liver and 0.077 mGy/MBq for spleen) used by the International Commission on
      Radiological Protection (ICRP). For (111)In-labeled thrombocyte study the doses
      were 0.33 +/- 0.05 (liver) and 8.9 +/- 1.2 mGy/MBq (spleen) versus 0.730 and
      7.50, respectively. The differences in dose estimates in the (111)In-labeled
      thrombocyte study are mainly due to the approximation used in activity
      quantitation. Convolution of the activity distribution with a point dose kernel
      is an effective method for calculating absorbed dose distribution in a
      homogeneous media. Activity distribution must be aligned to anatomical data in
      order to utilize the calculated dose distribution. The program developed is
      applicable to and practical for clinical use provided that the input data needed
      are available.

PMID- 9559957
TI  - Relationship between skeletal uptake of 99mTc-HMDP and bone mineral density in
      elderly women.
AB  - The relationship between bone mineral density in elderly women and the pattern of
      skeletal uptake of 99mTc-HMDP, especially in regard to skull uptake, was
      investigated. The whole-body skeletal uptake (WBSU) and whole-body skeletal
      tracer distribution patterns were studied in 86 disease-free women on bone
      scintigraphy with 99mTc-hydroxy-methylene-diphosphonate (HMDP). Bone scans were
      quantified by setting regions of interest (ROI) and bone mineral density (BMD)
      was assessed by dual-energy X-ray absorptiometry in all patients. WBSU and the
      skeletal distribution pattern were compared with bone mineral densities of the
      entire skeleton as well as selected regions. WBSU was high in the elderly and
      negatively correlated with regional bone mineral densities (r = -0.403 to 
      0.534). Among the regions, uptake by the skull increased with age more than in
      other regions in women and had the highest negative correlation with the bone
      mineral density. The skull uptake correlated negatively with total body BMD (r = 
      0.583) and with lumbar BMD (r = -0.561, p < 0.0001). Our results show that
      increased radionuclide uptake in bone scintigraphy, especially skull uptake was
      associated with decreased bone mineral density in elderly women, so that,
      increased skull uptake in elderly women would be a scintigraphic sign of post
      menopausal or senile osteopenia.

PMID- 9559956
TI  - Application of a beta microprobe for quantification of regional cerebral blood
      flow with (15)O-water and PET in rhesus monkeys.
AB  - A beta microprobe was successfully applied to monitor arterial input function for
      quantification of regional cerebral blood flow (rCBF) in the monkey brain with
      (15)O-water and positron emission tomography (PET). The sensitivity of the probe
      was approximately 0.83 to 1.67 cps/kBq/ml depending on the studies. A preliminary
      study was performed to find a suitable use and to evaluate the performance of the
      system and data analysis procedure. The results showed that dispersion correction
      of measured input function was unnecessary if microprobes were connected directly
      to the arterial catheter. Then multiple CBF measurements were done in three
      monkeys under anesthesia. Identical regions of interest were placed with the aid
      of magnetic resonance imaging (MRI) of each monkey and rCBF values were
      estimated. Estimated rCBFs were reproducible for several measurements. The mean
      CBF value for a pentobarbital anesthetized monkey was 46.0 ml/min/100 g (PaCO2 =
      46.3 mmHg). This shows that the use of the beta microprobe for quantification of
      rCBF with PET was validated. The lack of a need for dispersion correction of
      observed input function is an advantage with the beta microprobe system because
      the probes are small enough to be placed near the arterial sampling site.

PMID- 9559958
TI  - Acetazolamide induced myocardial ischemia in patients with severe coronary artery
      disease.
AB  - Acetazolamide (ACZ)-augmented brain SPECT is commonly used for evaluating
      cerebral vascular reserve in patients with cerebrovascular disease. ACZ may cause
      myocardial ischemia in patients with coronary artery disease. To evaluate the
      risk of induction of myocardial ischemia with ACZ-augmented myocardial SPECT, we
      performed combined ACZ-augmented Tl-201 myocardial SPECT (ACZ-myo SPECT) with Tc
      99m HMPAO brain SPECT in patients with severe coronary artery disease. METHODS:
      Nine patients underwent combined ACZ-myo SPECT with Tc-99m HMPAO brain SPECT. (1)
      For qualitative analysis, SPECT images were divided into 13 segments to calculate
      the total defect scores. (2) Six ROIs were placed on the slices in the myocardial
      SPECT short-axis images and the regional uptake ratio was obtained as the ratio
      of the mean counts in the myocardium to the maximal count in the slice. The total
      defect score and regional uptake ratio of ACZ-myo SPECT were compared with those
      of early and delayed dipyridamole Tl-201 myocardial SPECT (DP-Tl SPECT) images.
      RESULTS: (1) In the 21 coronary artery territories with coronary stenosis > or =
      75%, the total defect score in ACZ-myo SPECT, early and delayed DP-Tl SPECT
      images were 3.52 +/- 4.14*, 4.19 +/- 4.65* and 2.25 +/- 3.34, respectively (*: p
      < 0.05 vs. delayed DP-Tl SPECT images). (2) In 44 of 54 ROIs with coronary
      stenosis > or = 75%, the regional uptake ratio of ACZ-myo SPECT, early and
      delayed DP-Tl SPECT images were 0.670 +/- 0.166**, 0.677 +/- 0.194**, 0.721 +/-
      0.178, respectively (**: p < 0.01 vs. delayed DP-Tl SPECT images). Systolic blood
      pressure fell at 11 min after ACZ infusion without electrocardiographic ST-T
      changes or chest pain. CONCLUSION: As ACZ has the potential to cause myocardial
      ischemia, ACZ-augmented brain SPECT should be performed with caution in patients
      with severe coronary artery disease associated with cerebrovascular disease.

PMID- 9559959
TI  - Cerebral blood flow changes in the primary motor and premotor cortices during
      hyperventilation.
AB  - The aim of this study was to clarify the regional differences in cerebral blood
      flow (CBF) change during hyperventilation by using H2(15)O and positron emission
      tomography (PET). Eight healthy volunteers (age: 63.0 +/- 8.9 yr.) were studied.
      Regional CBF was measured by the H2(15)O autoradiographic method and PET.
      Statistical parametric maps (SPM) and conventional regions of interest (ROI)
      analysis were used for estimating regional CBF differences in the normocapnic
      state with normal breathing and the hypocapnic state induced by hyperventilation.
      Total CBF decreased during the hypocapnic state. The SPM revealed that primary
      motor and premotor cortices were significantly activated by hyperventilation. In
      these areas absolute CBF values were significantly higher than those in the
      temporal, occipital and parietal lobes in the hypocapnic state, but there were no
      significant regional differences in the normocapnic state. In the hypocapnic
      state induced by hyperventilation, the primary motor and premotor CBF shows
      combined changes with vasoreaction to hypocapnia and increase in activation due
      to hyperventilation.

PMID- 9559960
TI  - Cerebral muscarinic acetylcholinergic receptor measurement in Alzheimer's disease
      patients on 11C-N-methyl-4-piperidyl benzilate--comparison with cerebral blood
      flow and cerebral glucose metabolism.
AB  - We studied the cerebral muscarinic acetylcholinergic receptor (mACh-R) by means
      of 11C-N-methyl-4-piperidyl benzilate (11C-NMPB) and positron emission tomography
      (PET) in Alzheimer's disease (AD) cases, and the findings were compared with the
      cerebral blood flow (CBF) and the glucose metabolism (CMRGlc) to evaluate the
      relationship between the mACh-R and the CBF or the CMRGlc. The subjects consisted
      of 18 patients with AD and 18 age and sex matched normal volunteers. The patients
      were clinically diagnosed according to the criteria of the NINDS-ADRDA as having
      "probable AD" and were thus classified into two groups (mild and moderate AD)
      according to the severity of dementia determined by DSM-III-R. The CBF was
      measured by 99mTc-HMPAO SPECT, and the CMRGlc was measured by 18FDG PET. The 11C
      NMPB uptake was evaluated by the graphical method and the ratio method
      (ROIs/Cerebellum). A significant mACh-R decrease and more severe CMRGlc decrease
      in the cortical region was seen in mild and moderate AD. The decrease in the CBF
      was not as obvious as that in the mACh-R and the CMRGlc. Our study thus suggested
      that the mACh-R decreased in patients with AD, and that the 18FDG PET was the
      most sensitive method for detecting the degenerative regions in patients with AD.

PMID- 9559961
TI  - Absent myocardial accumulation of two different radioiodinated pentadecanoic
      acids.
AB  - This article presents two cases with preserved myocardial 201Tl uptake and absent
      uptake of two kinds of radioiodinated fatty acids: iodine-123-labeled 15-(p
      iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and iodine-123-labeled 15-(p
      iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA). Although coronary
      angiography showed no stenotic lesion and left ventriculography revealed no wall
      motion abnormality, no myocardial uptake of BMIPP and 9MPA was observed in the
      first case. In the second case, no myocardial accumulation was recognized even in
      the initial phase of dynamic SPECT acquired soon after the injection of 9MPA. The
      results suggest that the non-visualized myocardium was not specific for BMIPP
      imaging and that rather than the early back diffusion of the tracers from the
      myocardium, abnormality of the myocardial cell membrane was a possible mechanism
      accounting for the phenomenon.

PMID- 9559962
TI  - Four cases of Warthin's tumor of the parotid gland detected with FDG PET.
AB  - In the cancer screening with FDG PET for 1,872 medical health club members, high
      FDG accumulation in the parotid gland was found in four males (age, 57-70 years).
      Warthin's tumor was confirmed by surgical pathology. The exact mechanism of high
      FDG accumulation in Warthin's tumor is not yet known. This tumor may be found
      incidentally during FDG PET studies. When high FDG accumulation is found in the
      parotid gland, integrated consideration of the results of the physical
      examination, medical history and 99mTc-pertechnetate scintigraphy makes it
      possible to differentiate Warthin's tumor from other lesions.

PMID- 9559963
TI  - Gallium-67-citrate scintigraphy of primary renal lymphoma.
AB  - We present a case of primary renal lymphoma, which is a rare entity and poses
      diagnostic challenge. Ultrasound and CT scan demonstrated a nonspecific solid
      tumor in the left kidney. 67Ga-citrate scintigraphy demonstrated an intense
      uptake in the tumor, which led to a correct diagnosis, so that we could spare
      unnecessary laparotomy and possible nephrectomy.

PMID- 9559964
TI  - Metabolite analysis of [11C]flumazenil in human plasma: assessment as the
      standardized value for quantitative PET studies.
AB  - Analysis of carbon-11 labeled metabolites in plasma was carried out during
      positron emission tomography (PET) studies with a central benzodiazepine receptor
      ligand [11C]flumazenil ([11C]FMZ) in 24 human subjects (14-76 y.o.) including
      five normal volunteers and 19 patients with neurological disorders. Arterial
      plasma samples were obtained at 3, 5, 10, 15, 20, 30 and 60 min after i.v.
      injection of the tracer, and were analyzed by high-performance liquid
      chromatography. The rate of plasma [11C]FMZ degradation was associated with a
      large individual variation, but no significant difference was found in the
      degradation of [11C]FMZ either between male and female, young and old, or between
      normal subjects and patient groups. When the mean fraction of unchanged [11C]FMZ
      at each time point was used instead of individually measured metabolite data for
      the arterial input function, as much as a 30% error occurred in the distribution
      volume of the [11C]FMZ binding in the brain. These results indicate that the mean
      percentage of unchanged [11C]FMZ fraction in subjects cannot be used as the
      standardized value, and that the analysis of metabolites in plasma is necessary
      to determine the exact arterial input function for quantitative PET measurement.

PMID- 9559965
TI  - Acute cellular damage in medial smooth muscle cells following experimental
      coronary angioplasty in dog. Damage of cytoskeleton and apoptosis.
AB  - The purpose of the present study was to investigate the responses of the
      cytoskeleton and the presence of apoptosis following acute damage of medial
      smooth muscle cells after percutaneous transluminal coronary angioplasty (PTCA).
      We killed 20 dogs, 4h and 4 days after PTCA (n=10 in each group). Ten dogs
      without PTCA were used as controls. PTCA was achieved by inflating balloon
      catheters two times, for 60s each time, to 150 PSI, followed by a 60-s deflation.
      The coronary artery obtained from each dog was fixed in 10% formalin neutral
      buffer solution. The response of the cytoskeleton was studied
      immunohistochemically. using monoclonal antibodies against alpha-smooth muscle
      actin, vimentin, and beta-tubulin. Proliferation was determined by proliferating
      cell nuclear antigen (PCNA), and DNA fragmentation indicating apoptosis was
      determined by in situ nick end labeling. Four h after PTCA, endothelial
      denudation, microscopic mural thrombi, rupture of the internal elastic membrane,
      medial tear, and stretched smooth muscle cells with nuclei were found at the PTCA
      site. An immunohistochemical study revealed diffuse reduction or defective
      immunoreactivity in each cytoskeleton of medial smooth muscle cells, 4h after
      PTCA. The extent of positive immunoreactivity in the media decreased to 45+/-11%
      in alpha-smooth muscle actin (control value, 80+/-10%), 9+/-8% in vimentin
      (control value, 83+/-9%), and 10+/-7% in beta-tubulin (control value, 75+/-8%).
      The decrease was more significant in vimentin and beta-tubulin than in alpha
      smooth muscle actin. Four days after PTCA, the features were diffuse cell death
      and the focal proliferation of medial cells, as well as macroscopic intramural
      thrombi. The extent of positive immunoreactivity in the media was 15+/-9% in
      alpha-smooth muscle actin, 13+/-7% in vimentin, and 14+/-11% in beta-tubulin.
      There were no smooth muscle cells with positive PCNA (0%) in the control and 4-h
      groups, but 4 days after PTCA the percentage was 19+/-4%. In situ nick end
      labeling showed DNA fragmentation in the nuclei of medial smooth muscle cells at
      a rate of 15+/-5% 4h after PTCA and at 8+/-6% 4 days after PTCA, compared with 0%
      in the control. We concluded that severe damage of the cytoskeleton and medial
      smooth muscle cell death were induced immediately after PTCA, followed by
      proliferation of smooth muscle cells. Apoptosis may be partially involved in the
      death of smooth muscle cells, in addition to necrosis. Damage to the cytoskeleton
      and apoptosis may play an important role in the pathogenesis of acute lesions and
      the proliferation of smooth muscle cells after PTCA.

PMID- 9559966
TI  - Feasibility of diagnosing chronic myocarditis by endomyocardial biopsy.
AB  - In studies of all the layers of autopsied hearts from patients with chronic
      myocarditis, local clusters of lymphocytes are frequently noted, in contrast with
      hearts obtained from patients with acute myocarditis. Myocardial biopsy
      specimens, however are no larger than about 2mm x 3mm. With this in mind, the
      present study was undertaken to determine whether chronic myocarditis can be
      diagnosed by endomyocardial biopsy. Specimens were obtained from seven patients
      in whom chronic myocarditis was confirmed by the clinical course and by autopsy
      findings. In H&E stained specimens, sites corresponding to the biopsy sites in
      both ventricles (right ventricular free wall, right ventricular side of the
      ventricular septum, left ventricular lateral wall) were selected at random (five
      sites each from the right and left ventricles in each patient) and examined under
      a light microscope. A mean of 5 or more lymphocytes per visual field (by light
      microscopy at 400-fold magnification), a proposed quantitative diagnostic
      criterion of myocarditis, was noted in the right ventricle in three patients (5
      lymphocytes in two patients and 6 in one patient) and in the left ventricle in
      one patient (5 lymphocytes). Also, when the presence of lymphocyte clusters,
      considered to be a characteristic feature of chronic myocarditis, was determined,
      clusters of 20 or more lymphocytes per visual field were found in the same
      patients as those mentioned above, namely, in three patients (42.8%) in the right
      ventricle, as mentioned above, and in one patient (14.3%) in the left ventricle.
      At the sites of these lymphocyte clusters. findings such as degenerative changes
      of the myocardial cells and interstitial fibrosis were also associated, making
      possible a diagnosis of myocarditis. Therefore, in chronic myocarditis, even if
      five specimens are obtained by right ventricular biopsy, in approximately one
      half of patients the diagnosis of chronic myocarditis will be missed because of
      sampling errors.

PMID- 9559967
TI  - Altered distribution of collagen type I and hyaluronic acid in the cardiac
      outflow tract of mouse embryos destined to develop transposition of the great
      arteries.
AB  - Complete transposition of the great arteries (TGA) is inducible by treatment with
      all-trans retinoic acid in the ICR mouse. In this model, hypoplasia and dysplasia
      of the proximal outflow tract cushion tissue lead to non-spiral septation. In
      order to evaluate the effect of retinoic acid on the extracellular matrix of the
      cardiac outflow tract, we examined the distribution of collagen type I and
      hyaluronic acid, immunohistochemically, on days 8-9 of gestation. In controls,
      collagen type I fibrils ran mainly in a radial direction, extending towards the
      endocardium in the cardiac jelly of the proximal outflow tract. Also, a pair of
      longitudinal fiber bundles were formed stretching to the distal outflow tract. As
      for hyaluronic acid, intense staining was observed in the submyocardial and
      intermyocardial space of the outer curvature of the heart. On the other hand, in
      retinoic acid-treated embryos, the submyocardial radial fibrils or longitudinal
      fiber bundles of collagen type I were diminished, and irregular and dense
      deposits of collagen type I were observed along the endocardium. Furthermore,
      hyaluronic acid showed a loss of differential localization between the outer and
      inner curvature. Instead, irregular and intense staining was observed uniformly
      along the outflow myocardium. Thus, retinoic acid appeared to have perturbed the
      differentiation in the proximal outflow tract causing an altered organization of
      multiple extracellular matrix molecules, including collagen type I and hyaluronic
      acid, which led to an abnormal molecular network of the cardiac jelly in the
      cardiac outflow tract, abnormal septation and, further, to TGA or TGA-type
      anomalies.

PMID- 9559968
TI  - Acetylcholine-induced vasoconstrictor response of coronary vessels in rats: a
      possible contribution of M2 muscarinic receptor activation.
AB  - A mechanism by which acetylcholine (ACh) may elicit vasoconstrictor response in
      coronary vessels was studied in rat hearts perfused at a constant flow rate. In
      spontaneously beating hearts, bolus injections of ACh and carbachol (CCh)
      produced biphasic changes in coronary perfusion pressure (CPP): a transient
      increase at the initial period followed by a sustained decrease. In KCl-arrested
      hearts, ACh and CCh produced a monophasic increase in CPP, which was attenuated
      by either removal of endothelial cells by saponin or cyclooxygenase inhibition by
      diclofenac sodium. In the spontaneously beating heart, ACh-induced
      vasoconstriction was almost abolished by atropine (0.1 microM) and was markedly
      attenuated by an M2 antagonist, methoctramine (0.1 microM), but not by an M1
      antagonist, pirenzepine (1 microM). Arecaidine propargyl ester (APE), an M2
      agonist, produced coronary artery constriction which was attenuated by
      methoctramine (0.1 microM) but not by pirenzepine (0.1 microM) in both
      spontaneously beating and KCl-arrested hearts. McN-A-343, an M1 agonist,
      increased CPP in both beating and KCl-arrested hearts, but to a lesser degree
      than APE. These results suggest that the release of vasoconstrictor
      prostaglandins from endothelial cells contributes to the vasoconstrictor response
      to ACh in perfused rat coronary vessels, and the response to ACh appears to be
      mediated, in part, via the M2 subtype of muscarinic receptors.

PMID- 9559969
TI  - Effect of regional myocardial perfusion abnormalities on regional myocardial
      early diastolic function in patients with hypertrophic cardiomyopathy.
AB  - Nonuniform hypertrophy of the left ventricle is an important factor in regional
      diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM).
      However, the effect of myocardial perfusion abnormalities on regional diastolic
      dysfunction has not been established in patients with HCM. We investigated the
      relationship between regional myocardial perfusion abnormalities and regional
      early diastolic function in 31 patients with HCM and 8 control patients. Short
      axis images of the left ventricle recorded by cine magnetic resonance imaging
      were divided into ten blocks. The time-to-peak-wall-thickness-thinning rate
      (TPWR) and the wall thickness were measured in each block. Of the 310 blocks from
      the patients with HCM, 242 (78%) showed normal thallium-201 uptake (group 1), 40
      (13%) showed slightly decreased uptake (group 2), and 28 (9%) showed markedly
      decreased uptake (group 3). There was no difference in the regional wall
      thickness among the three groups. The TPWR was longer in patients with HCM than
      in control patients. It was significantly longer in group 3 (190+/-45ms) than in
      group 1 (167+/-36 ms) and group 2 (160+/-31 ms). (P < 0.01). The linear
      regression slope of the relationship between the TPWR and the regional wall
      thickness was significantly steeper in group 3 than in groups 1 and 2 (P < 0.05).
      In conclusion, abnormalities in regional myocardial perfusion, in addition to
      regional hypertrophy, contributed to the regional early diastolic dysfunction in
      patients with HCM.

PMID- 9559970
TI  - Successful treatment of intraoperative pulmonary tumor embolism from renal cell
      carcinoma.
AB  - During left nephrectomy in a 35-year-old woman with a left renal cell carcinoma
      extending into the inferior vena cava (IVC) and right atrium, cardiac arrest
      occurred. Immediate transesophageal echocardiography demonstrated that the event
      was caused by a pulmonary tumor embolism. Emergent cardiopulmonary bypass (CPB)
      was established and the tumors in the pulmonary arteries were successfully
      removed. The left nephrectomy was completed. The patient recovered in the
      intensive care unit without any neurological deficit. A postoperative pulmonary
      perfusion scintigram showed no defect in the pulmonary circulation.
      Transesophageal echocardiography was useful for making a rapid diagnosis of an
      intraoperative pulmonary embolism originating from a tumor of the IVC or right
      atrium.

PMID- 9559971
TI  - Syncope at sleep onset in a patient with nasopharyngeal carcinoma.
AB  - A patient with nasopharyngeal carcinoma developed atypical parapharyngeal-lesion
      syncope syndrome associated with stereotypical cycles of heart rate variation,
      which occurred only when he was drowsy before falling asleep. Vagal tone
      fluctuation is implicated.

PMID- 9559972
TI  - Immune responses to stress proteins: applications to infectious disease and
      cancer.
AB  - Heat shock proteins, or stress proteins have been identified as part of a highly
      conserved cellular defence mechanism mediated by multiple, distinct gene families
      and corresponding gene products. As intracellular chaperones, stress proteins
      participate in many essential biochemical pathways of protein maturation and
      function active during times of stress and during normal cellular homeostasis. In
      addition to their well-characterized role as protein chaperones, stress proteins
      are now realized to possess another important biological property:
      immunogenicity. Stress proteins are now understood to play a fundamental role in
      immune surveillance of infection and malignancy and this body of basic research
      has provided a framework for their clinical application. As key targets of both
      humoral and cellular immunity during infection, stress proteins have accordingly
      received considerable research interest as prophylactic vaccines for infectious
      disease applications. The unique and potent immunostimulatory properties of
      stress proteins have similarly been applied to the development of new approaches
      to cancer therapy, including both protein and gene-based modalities.

PMID- 9559973
TI  - HLA-DR/DQ transgenic, class II deficient mice as a novel model to select for HSP
      T cell epitopes with immunotherapeutic or preventative vaccine potential.
AB  - Protective immunity against mycobacteria is dependent on antigen/MHC class II
      specific, CD4+ Th1 cells. HLA-DR3-restricted Th1 cells respond to a subset of
      mycobacterial antigens, including the immunodominant hsp65, and recognize a
      single epitope in hsp65, notably p1-20. Altered peptide ligands (APL) of p1-20
      can inhibit p1-20/hsp65-induced proliferation of DR3-restricted T cells in an
      allele specific manner in vitro. In order to develop a preclinical model in which
      p1-20 APL can be tested in vivo in the context of HLA, we have used murine class
      II deficient, HLA transgenic (Ab0) mice, in which all CD4+ T cells are restricted
      by the tg HLA molecule. BCG-immunized DR3.Ab0 and DQ8.Ab0 mice both responded
      well to hsp65. Furthermore, DR3.Ab0 mice recognized precisely the same p1-20
      epitope as DR3-restricted human T cells, whereas DQ8.Ab0 mice responded to a
      different set of hsp65 peptides. This shows that (i) the same immunodominant
      protein and peptide epitope are recognized by T cells from DR3.Ab0 mice and DR3+
      humans and (ii) indicates the major role of HLA-polymorphism in controlling the
      human T cell response to mycobacterial antigens. Thus, HLA-transgenic, Ab0 mice
      provide a novel, preclinical model system to analyze APL and vaccines in the
      context of HLA polymorphism.

PMID- 9559974
TI  - Heat shock proteins as potential targets in the therapy of inflammatory
      arthritis.
AB  - Whether heat shock proteins (hsp) will be therapeutic targets in arthritis
      depends on their role in pathogenesis. In this article, three possibilities are
      considered. Firstly, an excessive immune response to bacterial hsp could be
      arthritogenic - as may occur in reactive arthritis. In these circumstances
      therapy would be directed to down-regulating this immune response, or altering
      the nature of the immune response e.g. by changing cytokine production from
      interferon-g to IL-4. However this approach depends on the immune response to
      bacterial hsp not being critical for control of the bacterial infection.
      Secondly, an immune response to bacterial hsp may induce autoimmunity by cross
      reactivity, e.g. with the homologous human. This could also be modulated in the
      same way with a lower likelihood of interfering with control of the infectious
      agent, since only a component of the immune response against the bacterial hsp
      will be cross-reactive with self. Thirdly, recent experiments raise the
      possibility that joint inflammation might be controlled by T cells which
      recognizes self hsp, particularly hsp60. Therapies might enhance this response;
      protection from experimental arthritis by prior immunization with hsp60 is well
      established. Whether similar approaches will be viable after arthritis is
      established remains to be seen.

PMID- 9559975
TI  - Nasal administration of arthritis-related T cell epitopes of heat shock protein
      60 as a promising way for immunotherapy in chronic arthritis.
AB  - Adjuvant Arthritis (AA) can be induced in Lewis rats by immunisation with
      mycobacterial antigens. The disease can be passively transferred with T cell
      clone A2b, which recognises the 180-188 amino acid sequence in mycobacterial heat
      shock protein 60 (hsp60) and which crossreacts with crude cartilage
      proteoglycans. We succeeded to induce peripheral tolerance to this AA-associated
      T cell epitope following nasal administration of a peptide containing this
      epitope (mycobacterial hsp60 176-190). In rats treated nasally with 176-190 and
      immunised with mycobacterial hsp60, proliferative responses to 176-190 were
      reduced. AA was inhibited nasally with 176-190 treated rats and not in rats
      nasally treated with a control mycobacterial hsp60 peptide (211-225). Moreover,
      nasal 176-190 led to similar arthritis protective effects in a non-microbially
      induced experimental arthritis (avridine induced arthritis). In a subsequent
      study we tried to prevent and to treat AA through nasal administration of
      mycobacterial hsp60 peptide 180-188 and a peptide analogue of 180-188, 180
      188(L183->A) (Alanine 183), which has been shown to have an increased MHC-binding
      affinity for rat RT1 Bl and an increased capacity to inhibit the proliferative
      A2b response in vitro. We found that nasal administration of 180-188 had a
      moderate arthritis suppressive effect in AA, whereas its analogue peptide Alanine
      183, had a strong suppressive effect. This strong arthritis suppressive effect
      was only partly due to the higher MHC-binding affinity for rat RT1 Bl.
      Furthermore, it was possible to passively transfer nasal Alanine 183 induced
      disease protection. The present findings may in our view offer novel prospects
      for immunotherapy through nasal administration of (analogue) peptides, with a
      mimicry relationship with joint specific cartilage proteoglycan epitopes.

PMID- 9559976
TI  - Mucosal modulation of immune responses to heat shock proteins in autoimmune
      arthritis.
AB  - Induction of oral tolerance to antigens that are targets of self-reactive immune
      responses is an attractive approach to antigen-specific immune therapy of
      autoimmune diseases. Oral tolerization has indeed proven to be safe and effective
      in amelioration of autoimmune diseases in animal models. In humans, results have
      been somewhat controversial. The emphasis given to clinical outcome rather than
      to immunomodulation, and the difficulty in identifying appropriate candidate
      antigens contribute to the controversy. Heat shock proteins are promising targets
      for immune intervention. Immune reactivity to heat shock proteins has indeed been
      correlated with autoimmune arthritis in animal models, and abnormal immune
      responses to heat shock proteins have been described in human arthritis as well.
      Despite significant recent progress, little is known at a molecular level
      regarding the mechanisms which are responsible for a switch from autoimmunity to
      tolerance in humans. This is particularly true with respect to sequential
      analysis of several molecular and immunologic markers during both the course and
      treatment of disease. Novel approaches are currently under way to fill the gaps.
      We will briefly detail here the experience gained to date, and identify some of
      the avenues which future research will explore.

PMID- 9559978
TI  - Heat shock proteins and the antitumor T cell response.
AB  - Heat shock proteins (HSP) have been shown to participate in the antitumor T cell
      response. First, HSP play a crucial role in the intracellular pathway for antigen
      processing where HSP can make complexes with a broad spectrum of cellular
      proteins and peptides through their chaperone functions. In this pathway,
      macrophages are required for processing the chaperoned peptides to make stable
      molecules with the major histocompatibility complex (MHC) class I molecules, even
      when HSP-peptide complexes are exogenously administered. Through this pathway,
      vaccination with HSP-peptide complexes is thus able to elicit the response of
      CD8+ T cells specific for the chaperoned peptides. These findings suggest an
      essential role of HSP in 'cross-priming' and their usefulness for antitumor
      vaccination with tumor peptides. Second, HSP have been suggested to be expressed
      on the cell surface by transformation and, in addition, to function as antigen
      presenting molecules for double negative T cells. Third, HSP derived from tumor
      cells have reportedly been recognized by T cells with either T cell receptor
      (TCR)-alphabeta or TCR-gammadelta. These lines of evidence therefore indicate
      that HSP may be potentially promising target molecules for antitumor T cell
      immunotherapy.

PMID- 9559977
TI  - Oral administration of HSP-containing E. coli extract OM-89 has suppressive
      effects in autoimmunity. Regulation of autoimmune processes by modulating
      peripheral immunity towards hsp's?
AB  - OM-89 (Subreum) is an E. coli extract used for oral administration in the
      treatment of rheumatoid arthritis. It contains bacterial heat shock proteins,
      namely hsp60 and hsp70, which were shown to be major immunogenic constituents of
      the drug. Immunity to bacterial heat-shock antigens was shown to be a means of
      immunomodulation of (experimental) autoimmune disease and possibly inflammation
      in general. This was demonstrated for mycobacterial hsp60 respectively hsp70 in
      autoimmune disease models for arthritis, diabetes and encephalitis. Parallel to
      the effects displayed by immunisation with hsp, oral administration of hsp
      containing OM-89 was found to modify autoimmune disease in a number of animal
      models, such as for arthritis, diabetes and SLE. In rats immunisation with OM-89
      was found to lead to proliferative T cell responses to hsp60 and hsp70 of both E.
      coli and mycobacterial origin. Conversely, immunisation with hsp antigens could
      induce T cell reactivity specific for OM-89. Given this and the autoimmune
      disease modulating properties of both hsp and OM-89 it is argued that OM-89 acts
      via the same mechanism as proposed for hsp: that peripheral tolerance is induced
      at the level of regulatory T cells with specificity for heat-shock proteins. This
      may constitute one mode of action for OM-89 as an arthritis suppressive oral drug
      in man.

PMID- 9559979
TI  - Antigen-specific therapies in multiple sclerosis.
AB  - Multiple sclerosis is the major neurological disease of young adults in the
      western world, affecting about 1 per 1,000. It is characterised by chronic or
      recurrent lesions of inflammatory damage in the white matter of the central
      nervous system. Within such lesions, the protective myelin sheath is stripped off
      axons by infiltrated macrophages which leads to impaired conductivity. The
      inflammatory process most likely starts by activation of helper T cells directed
      against local myelin antigens. Currently, efforts are directed at specifically
      blocking such myelin-reactive helper T cells in order to control the disease. In
      this chapter, immunological features of multiple sclerosis and the experimental
      animal model for the disease, experimental allergic encephalomyelitis, are
      discussed. Next, an overview is presented on myelin antigens that have been
      suggested to play a role as target antigens in MS. Finally, strategies are
      discussed that are currently employed to selectively block the activation of T
      cells reactive against myelin antigens.

PMID- 9559980
TI  - Muscle fiber type compartmentalization and expression of an immature myosin
      isoform in the sternocleidomastoid muscle of rabbits and primates.
AB  - The sternocleidomastoid muscle is located in the neck and is both a neck rotator
      and flexor. Cervical dystonia, a focal dystonia disorder, is characterized by
      forceful involuntary contraction of a group of neck muscles, usually including
      the sternocleidomastoid. Little is known about the fiber type composition, fiber
      type compartmentalization and innervation patterns in this muscle in rabbit and
      primates. Sternocleidomastoid muscles from rabbit and monkey were analyzed for
      muscle fiber type composition and number, muscle fiber cross-sectional area and
      patterns of innervation. The sternocleidomastoid muscle was composed of two
      distinct regions, or compartments, with different fiber type compositions: an
      outer or superficial region composed of mostly type 2 myofibers and an inner deep
      region composed of both type 2 and type 1 myofibers. Neonatal myosin heavy chain
      isoform was detected in approximately 25% of the myofibers in both regions of the
      muscle. Neuromuscular junctions were located in seven endplate bands
      approximately 1-3 cm apart throughout the length of the muscle. There is clear
      evidence of anatomical subdivisions within this muscle. Not only is there
      variation in fiber type composition between superficial and deep regions of the
      muscle, but unlike most other mature skeletal muscles, it continues to express
      neonatal myosin heavy chain isoform in the adult. The motor program for neck
      movements is extremely complex, and the histological complexity plays a role in
      allowing for a continuum of movements of the head and neck, from maintenance of
      posture to rapid head movements.

PMID- 9559981
TI  - Selective involvement of large motor neurons in the spinal cord of rats treated
      with methylmercury.
AB  - Mercury is thought to be a possible epidemiological factor for the pathogenesis
      of motor neuron disease, since it has been reported that metallic, inorganic and
      organic mercury causes a syndrome clinically resembling amyotrophic lateral
      sclerosis. We administered 10 mg/kg/day methylmercury chloride to adult rats for
      10 consecutive days. The hind-limbs became flaccid and atrophic, and 14 out of
      the 34 rats had died by the 18th day after methylmercury treatment began. Light
      microscopical examination of the large motor neurons in the spinal anterior horn
      revealed cytoplasmic vacuolation and loss of Nissl substance on the 14th day, and
      neuronophagia appeared on the 16th day. On the 18th day, the loss of large motor
      neurons was almost complete, whereas small to medium-sized neurons were
      preserved. Silver acetate autometallography to detect mercury revealed the
      selective accumulation of mercury in the large motor neurons. These findings
      suggest that although a high dose is required, organic mercury can cause the
      definite loss of large spinal motor neurons in rats.

PMID- 9559982
TI  - Polyneuropathy due to cobalamin deficiency in the rat.
AB  - In the present study, we investigated the peripheral nervous system (PNS) (both
      in terms of its ultrastructure and in terms of its function) of rats made
      cobalamin (Cbl)-deficient either through total gastrectomy or through prolonged
      feeding on a Cbl-deficient diet. In both these types of Cbl-deficient
      neuropathies we found: (a) ultrastructurally, intramyelin and endoneural edema,
      with no or minimal axonal damage in the PNS, in dorsal root ganglia, and the
      ventral and dorsal rootlets of the spinal cord; (b) electrophysiologically, a
      significant reduction in the nerve conduction velocity, consistent with that
      reported in (a); (c) morphometrically, a significant reduction in the density of
      myelinated fibers both in the sciatic nerve and in the peroneal nerve. All these
      pathological changes were reversed by chronic postoperative administration of Cbl
      into totally gastrectomized (TGX)-rats, hinting at the specificity of the damage
      itself in relation to the permanent Cbl-deficient status of the TGX-rats. No
      signs of segmental demyelination or remyelination were found. We also observed a
      turning of type I fibers into type II fibers in the soleus muscle of all our Cbl
      deficient rats, however the Cbl deficiency had been induced. This muscular change
      was still present in TGX- and Cbl-treated rats, and it cannot be related to a
      malnutrition status, since it has been observed also in rats fed a Cbl-deficient
      diet. All these results demonstrate that Cbl deficiency strongly affects rat PNS
      within different parameters.

PMID- 9559983
TI  - A novel splicing mutation in the ceruloplasmin gene responsible for hereditary
      ceruloplasmin deficiency with hemosiderosis.
AB  - Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a
      newly recognized autosomal recessive disorder of copper-iron metabolism due to
      mutations in the ceruloplasmin (Cp) gene. We report here a novel mutation in the
      Cp gene in a 54-year-old Japanese woman with this disease. She showed clinical
      triad; diabetes mellitus, retinal degeneration and neurological disorder in her
      middle age. Laboratory findings were characteristic for no detectable serum
      ceruloplasmin and increased serum ferritin. Liver biopsy revealed excessive
      storage of iron in hepatocytes and magnetic resonance imaging of the brain was
      indicative of increased iron content in the basal ganglia, thalamus and dentate
      nucleus. The a-->g substitution at the splice acceptor site of the intron 6 (1209
      2) caused a 8-bp deletion in Cp mRNA by defective splicing, resulting in a
      premature termination codon at the amino acid position 388. Truncation of Cp,
      even if effectively translated, may cause loss of its normal function because of
      drastic change in its triangular structure.

PMID- 9559984
TI  - Intravenous immunoglobulin preparation increases myoplasmic calcium concentration
      by activating the dihydropyridine-ryanodine receptor complex.
AB  - A human intravenous immunoglobulin preparation (IVIg) released Ca2+ from the
      sarcoplasmic reticulum of cultured human skeletal muscle cells in a dose
      dependent manner. Blocking the dihydropyridine-ryanodine receptor complex
      abrogated the IVIg-mediated Ca2+ response, whereas inhibition of the voltage
      operated Na+-channels or acetylcholine receptors did not. This effect of IVIg was
      not mediated by its main component, the IgG molecules, and differed between
      preparations from different manufacturers. Heating destroyed the activity. Data
      shows that an unidentified serum protein present in IVIg can influence human
      muscle cells by an effect on the dihydropyridine receptor. This phenomenon may be
      important in interpreting the (side) effects of IVIg in neuromuscular diseases.

PMID- 9559985
TI  - A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10
      deficiency.
AB  - We report severe coenzyme Q10 deficiency of muscle in a 4-year-old boy presenting
      with progressive muscle weakness, seizures, cerebellar syndrome, and a raised
      cerebro-spinal fluid lactate concentration. State-3 respiratory rates of muscle
      mitochondria with glutamate, pyruvate, palmitoylcarnitine, and succinate as
      respiratory substrates were markedly reduced, whereas ascorbate/N,N,N',N'
      tetramethyl-p-phenylenediamine were oxidized normally. The activities of
      complexes I, II, III and IV of the electron transport chain were normal, but the
      activities of complexes I+III and II+III, both systems requiring coenzyme Q10 as
      an electron carrier, were dramatically decreased. These results suggested a
      defect in the mitochondrial coenzyme Q10 content. This was confirmed by the
      direct assessment of coenzyme Q10 level by high-performance liquid chromatography
      in patient's muscle homogenate and isolated mitochondria, revealing levels of 16%
      and 6% of the control values, respectively. We did not find any impairment of the
      respiratory chain either in a lymphoblastoid cell line or in skin cultured
      fibroblasts from the patient, suggesting that the coenzyme Q10 depletion was
      tissue-specific. This is a new case of a muscle deficiency of mitochondrial
      coenzyme Q in a patient suffering from an encephalomyopathy.

PMID- 9559986
TI  - Evolution of brain tuberculomas under standard antituberculous treatment.
AB  - The treatment of brain tuberculomas is primarily medical. Surgery, excision or
      biopsy, is generally performed when the diagnosis is in doubt or there is no
      response to medical therapy. The aim of this study was to determine the
      radiological evolution of intracranial tuberculomas under standard anti
      tuberculous drug therapy and to establish guidelines for better management of
      these patients. Eighteen patients were studied retrospectively. None of them had
      surgical intervention and all were treated by standard antituberculous drugs and
      had serial computed tomography (CT) scans until disappearance or stabilization of
      brain lesions. The regression of lesions' size and number was slow in the first
      month (mean -7.3%) then became rapid after this (-15% to -20% per month). A
      paradoxical increase in size was noted in three patients in the first month. All
      three had associated meningitis. All tuberculomas disappeared on CT scan after 12
      months of therapy. Most of the edema images disappeared by 6 months. This study
      would suggest that a long treatment regimen of 15-18 months may not be necessary
      in most intracranial tuberculomas occurring in non-immunocompromised patients. It
      also demonstrates that medical trial in well tolerated suspected cases should
      last for at least 2 months before considering other etiologies or surgical
      exploration.

PMID- 9559987
TI  - Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients
      with central nervous system complications of HIV-1 infection: a correlation with
      blood-brain-barrier dysfunction.
AB  - As nitric oxide (.NO) is hypothesised to play a role in the immunopathogenesis of
      neurological complications associated with inflammation, we compared levels of
      cerebrospinal fluid (CSF) and serum .NO metabolites in 24 patients with HIV-1
      infection, to those in 58 non-HIV infected patients with neurological disorders.
      Levels of .NO metabolites were correlated with blood-brain-barrier dysfunction.
      CSF and serum nitrate and nitrite levels were measured by the nitrate reductase
      and Griess reaction methods. The .NO metabolites, nitrate and nitrite, were
      raised in the CSF and serum of patients with AIDS and central nervous system
      complications, when compared to non-HIV infected patients with inflammatory and
      non-inflammatory neurological disorders (median nitrate and nitrite: CSF=18.3
      microM vs. 11.1 microM vs. 7.0 microM, P<0.001, and serum=53.8 microM vs. 50.3
      microM vs. 41.4 microM, P=0.04, respectively). CSF nitrate and nitrite levels
      correlated with the albumin quotient. This study supports the evidence that .NO
      is a potential mediator of blood-brain-barrier breakdown in inflammatory diseases
      of the central nervous system.

PMID- 9559988
TI  - Alzheimer's disease: patterns of cognitive impairment at different levels of
      disease severity.
AB  - The aim of this study was to establish the presence and the consistency of
      different cognitive profiles in AD patients taking into consideration the
      severity of mental impairment. Therefore we stratified 679 neuropsychological
      observations on 119 probable AD patients followed longitudinally on the basis of
      overall degree of cognitive impairment. To compare performance on tests with
      different score ranges we transformed raw test scores into coefficients; to
      summarize our results in terms of language versus visuo-spatial performance we
      computed indices of prevalent impairment of performance (IPIP) by subtracting the
      coefficients for constructional praxis from coefficients for language-related
      tests. Finally, we converted these indices into z-scores for each level of mental
      decline to identify patients with generalized, language (L) or visuo-spatial (V)
      prevalent impairment. The latter, 30% of the sample, can be detected at all
      stages of dementia. There was a higher percentage of males among language
      impaired patients (P<0.05). Approximately half of patients with L/V prevalent
      impairment continued to show such a focality when followed longitudinally. The
      groups did not differ in the annual rate of cognitive decline.

PMID- 9559989
TI  - Impairment of mitochondrial function in skeletal muscle of patients with
      amyotrophic lateral sclerosis.
AB  - In skeletal muscle homogenates of 14 patients with sporadic amyotrophic lateral
      sclerosis, an approximately twofold lower specific activity of NADH:CoQ
      oxidoreductase in comparison to an age matched control group (n=28) was detected.
      This finding was confirmed by a detailed analysis of mitochondrial oxidative
      phosphorylation in skeletal muscle using saponin-permeabilized muscle fibers. (i)
      A significantly lowered maximal glutamate+malate and pyruvate+malate supported
      respiration of saponin-permeabilized fibers was detected in the patients group.
      (ii) Titrations with the specific inhibitor of NADH:CoQ oxidoreductase amytal
      revealed a higher sensitivity of respiration to this inhibitor indicating an
      elevated flux control coefficient of this enzyme. (iii) Applying functional
      imaging of mitochondria using ratios of NAD(P)H and flavoprotein autofluorescence
      images of saponin-permeabilized fibers we detected the presence of partially
      respiratory chain inhibited mitochondria on the single fiber level. A secondary
      defect of mitochondrial function due to the neurogenic changes in muscle seems to
      be unlikely since no mitochondrial abnormalities were detectable in biopsies of
      patients with spinal muscular atrophy. These results support the viewpoint that
      an impairment of mitochondria may be of pathophysiological significance in the
      etiology of amyotrophic lateral sclerosis.

PMID- 9559990
TI  - Crossed cerebellar diaschisis and brain tumor biochemistry studied with positron
      emission tomography, [18F]fluorodeoxyglucose and [11C]methionine.
AB  - Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum
      contralateral to the tumor side (crossed cerebellar diaschisis, CCD). We
      investigated whether CCD is related to tumor localization, histological grade,
      size and tumor biochemistry. Cerebellar glucose metabolism was measured in 44
      glioma patients and 15 healthy subjects using positron emission tomography and
      [18F]fluorodeoxyglucose (FDG). CCD was determined by calculating an asymmetry
      index of cerebellar glucose metabolism. Further, the tumor uptake of FDG and
      [11C]methionine (MET) was also assessed, and was expressed as ratio of normalized
      tracer uptake in tumor over contralateral cortex (T/C). Frontal lobe tumors were
      associated with highest CCD values. For these tumors, CCD was higher in malignant
      (-11.8+/-9.9%) than in low-grade (-4.3+/-4.1%) gliomas (P=0.010). In addition,
      frontal lobe tumors showed increasing CCD values with increasing size. In tumors
      of the parietal or temporal lobe, CCD was less marked or absent. T/C ratios of
      tumor tracer uptake were higher in malignant than in low-grade gliomas, but were
      not correlated with CCD. Our data indicate that the magnitude of CCD is mainly
      determined by tumor localization and size, the latter being associated with tumor
      grade. These findings raise the question whether CCD provides a measure of
      expansion or progression particularly in low-grade tumors of the frontal lobe.

PMID- 9559991
TI  - Proton magnetic resonance spectroscopy during transient global amnesia.
AB  - There is uncertainty about the etiology of transient global amnesia and none of
      the pathogenetic hypotheses proposed so far, i.e. transient ischemia, epileptic
      discharge and spreading depression of cortical electrical activity, is completely
      satisfactory. Using water suppressed proton magnetic resonance spectroscopy we
      studied one patient during a typical episode of transient global amnesia and 2
      weeks thereafter in order to investigate the metabolic changes in the hippocampal
      region. In both hippocampi, spectra of N-acetyl-aspartate, creatine
      phosphocreatine, compounds containing choline and lactate failed to show changes
      consistent with cerebral ischemia, both in the acute phase and in the follow-up.
      Spreading depression in response to emotional stress seems a likely explanation
      in this patient, who suffered from migraine in the past.

PMID- 9559992
TI  - Auditory and visual event-related potentials and flash visual evoked potentials
      in Alzheimer's disease: correlations with Mini-Mental State Examination and
      Raven's Coloured Progressive Matrices.
AB  - We investigated possible correlations among neurophysiological examinations
      [auditory and visual event-related potentials (A-ERPs, V-ERPs), and flash visual
      evoked potentials (F-VEPs)] and neuropsychological tests [Mini-Mental State
      Examination (MMSE) and Raven's Coloured Progressive Matrices (RCPM)] in 15
      subjects with probable or possible Alzheimer's disease (AD) according to the
      National Institute of Neurological and Communicative Disorders and Stroke and the
      Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
      The P300 latency of A-ERPs was correlated with the scores of MMSE but not with
      those of RCPM. The P300 latency of V-ERPs was more significantly correlated with
      the scores of RCPM than with those of MMSE. The P2 latency of F-VEPs was more
      significantly correlated with the scores of RCPM than with those of MMSE. The P2
      latency of F-VEPs was not correlated with the P300 latency of A-ERPs but was
      correlated with the P300 latency of V-ERPs. The close relationship among V-ERPs,
      F-VEPs and RCPM suggests that these examinations at least partly reflect the
      functions of visual association areas in AD. Furthermore, discrepancy between
      P300 latency by A-ERPs and V-ERPs suggests that the mechanism responsible for
      P300 generation is not identical between these two stimulus modalities.

PMID- 9559993
TI  - SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset
      pure cerebellar ataxia.
AB  - Spinocerebellar ataxia type 6 (SCA6) is caused by small CAG repeat expansion in
      the gene encoding the alpha1A-voltage-dependent-calcium channel subunit
      (CACNLIA4) on chromosome 19p13, and is a subgroup of the late-onset pure
      cerebellar ataxia (ADCA III). To investigate the prevalence of SCA6 in the
      Japanese, we analyzed this mutation in 23 families and 12 probands with ADCA III.
      The specificity and stability of the CAG repeat were examined in additional
      individuals and families with other miscellaneous dominant SCAs. The CAG
      expansion of SCA6 gene was exclusively observed in 12 of 23 families (52%) and 12
      proband cases with ADCA III, but not in others. The CAG repeat was 21-33 in the
      disease-associated alleles (n=56), and 4-18 in normal alleles (n=1148). Expanded
      alleles were stable during transmission, and a significant inverse correlation
      for CAG repeat number with age at onset was noted. Our results indicate that SCA6
      shares approximately half of the ADCA III in the Japanese, and that gene
      mutations causing the remaining, have yet to be identified.

PMID- 9559994
TI  - Transient tonic pupils in botulism type B.
AB  - We report a 29-year-old woman who developed unilateral unreactive mydriasis and
      cycloplegia after 5 days of persistent constipation. During the next hours the
      patient complained of dry mouth and difficulties in swallowing food; iris and
      ciliary muscle palsies spread over the second eye. Ocular motility was normal and
      there were no clinical signs of neuromuscular involvement. Conventional
      electromyography and evoked muscle action potentials following repetitive nerve
      stimulation were normal; single-fiber electromyography showed normal jitter and
      absence of blocking. The diagnosis of botulism was considered as most likely, and
      the patient was given botulinum antitoxin. The post-treatment course was
      characterized by bilateral tonic pupillary reaction to near, sectoral iris
      contractions to light and pupillary constriction to 2 mm in 40 min following
      topical instillation of 0.1% pilocarpine. Ocular manifestations completely
      disappeared within 5 weeks. Botulism type B toxin was demonstrated in the
      pretreatment stool of the patient but not the serum.

PMID- 9559995
TI  - Guillain-Barre syndrome associated with IgG anti-GM1b antibody subsequent to
      Mycoplasma pneumoniae infection.
AB  - Sera from patients with Guillain-Barre syndrome (GBS) frequently have antibodies
      to various gangliosides. We report a girl with GBS after Mycoplasma pneumoniae
      infection who had serum IgG antibody to GM1b ganglioside as well as the cold
      agglutinins. The cold agglutinins are polyclonal IgM autoantibodies to 'I'
      antigen on erythrocytes. Ganglioside GM1b contains the terminal moiety shared
      with sialylated I antigen, a main receptor for M. pneumoniae. In this patient,
      the anti-GM1b antibody may be elicited in a similar mechanism producing anti-I
      antibody, and functioned in the development of GBS.

PMID- 9559996
TI  - Plasma levels of neuroexcitatory amino acids in patients with migraine or tension
      headache.
AB  - Plasma amino acids were analysed in patients with migraine with (9) and without
      (80) aura, in patients with tension headache (14) and in controls (62). The
      neuroexcitatory amino acids glutamic acid, glutamine, glycine, cysteic acid and
      homocysteic acid were elevated in migraine patients while total thiols
      (cysteine/cystine) were reduced. Patients with tension headache had values which
      were similar to those of controls. Tryptophan was elevated in migraine patients
      without aura only. Studies on two patients showed that the raised resting
      excitatory amino acid levels became still further elevated during a migraine
      attack. These results show that high concentrations of neurotransmitter amino
      acids occur normally in migraine patients and suggest that this profile may be a
      contributory factor in migraine attacks. Tension headache, however, has different
      biochemical parameters.

PMID- 9559997
TI  - Exacerbation of myasthenia gravis during the menstrual period.
AB  - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder mediated by
      antiacetylcholine receptor antibodies. It has long been suspected to exacerbate
      during the menstrual period but this has never been adequately documented.
      SUBJECTS AND METHODS: We questioned 120 female myasthenic patients of different
      ages, about their myasthenic symptoms before and during the menstrual period. We
      also evaluated the effect of medications, pain and stress during or before the
      menstrual period on the exacerbation rate. Exclusion criteria were postmenopausal
      age and incomplete information available in the questionnaire. RESULTS: Forty two
      premenopausal women with generalized disease were included in the study. Twenty
      eight (67%) of the patients reported exacerbation of their myasthenic symptoms 2
      to 3 days prior to the menstrual period. This exacerbation persisted in 22 of
      them to the third day of the menstrual period. In nine of the women this clinical
      worsening necessitated an increased intake of medications during the days prior
      to menstruation. No correlation could be found between the presence of
      antiacetylcholine receptor antibodies, pain, stress, use of oral contraceptives
      or the type of antimyasthenic therapy and the rate of exacerbation before and
      during the menstrual period. CONCLUSIONS: (1) MG frequently exacerbates before
      and during the menstrual period in 67% of MG patients. (2) The rate of
      exacerbation is unrelated to the presence of stress or pain prior to or during
      the menstrual period. (3) Different therapies directed against MG, as well as
      oral contraceptives do not influence the clinical course. (4) Menstrual
      exacerbations occur in both seronegative and seropositive patients. (5) These
      exacerbations may frequently necessitate therapeutic changes.

PMID- 9559998
TI  - Multiple sclerosis presenting with a Brown-Sequard syndrome.
AB  - The Brown-Sequard syndrome as spinal hemiplegia with contralateral sensory
      deficits has been related to a variety of underlying diseases. We describe the
      case of a 35-year-old right-handed white female presenting with a Brown-Sequard
      syndrome as the first and sole symptom of multiple sclerosis, underscoring the
      importance of multiple sclerosis as a rare condition for the Brown-Sequard
      syndrome.

PMID- 9559999
TI  - Multiple system atrophy with severe involvement of the motor cortical areas and
      cerebral white matter.
AB  - We report multiple system atrophy (MSA) of 14 years' duration in a 75-year-old
      woman. Postmortem examination revealed pathological changes typical of MSA.
      Furthermore, neuronal loss with astrocytosis in the primary motor and premotor
      cortices, especially in the fifth and sixth layers, and extensive myelin and
      axonal loss in the frontal and parietal white matter were evident. There were
      numerous ubiquitin-positive oligodendroglial inclusions, which are characteristic
      of MSA, in these cortical and white matter lesions. These findings suggest that
      the motor cortical areas and cerebral white matter are sites of significant
      involvement in the MSA disease process and that inclusion-bearing
      oligodendroglial alterations contribute to the white matter degeneration.

PMID- 9560000
TI  - Comparative conformational studies on cyclic hexapeptides corresponding to
      message sequence His-Phe-Arg-Trp of alpha-melanotropin by NMR.
AB  - Solution conformation of cyclo(Gly1-His2-Phe3-Arg4-Trp5-Gly6) and its D-Phe
      analog corresponding to the message sequence [Gly-alpha-MSH5-10] of alpha-MSH has
      been studied by 1D and 2D proton magnetic resonance spectroscopy in dimethyl
      sulfoxide (DMSO)-d6 solution and in a DMSO-d6/H2O cryoprotective mixture. The NMR
      data for both the analogs in solution at 300 K cannot be interpreted based on a
      single ordered conformation, as evidenced by the broadening of only -NH
      resonances as well as the temperature coefficients of the amide protons. An
      analysis of the nuclear Overhauser effect (NOE) cross-peaks in conjunction with
      temperature coefficient data indicates an equilibrium of multiple conformers with
      a substantial population of particular conformational states at least in the D
      analog. The molecular dynamics simulations without and with NOE constraints also
      reveal numerous low-energy conformers with two gamma-turns, a gamma-turn and a
      beta-turn, two beta-turns, etc. for both the analogs. The observed NMR spectra
      can be rationalized by a dynamic equilibrium of conformers characterized by a
      gamma-bend at Gly6, two gamma-bends at Phe3 and Gly6 and a conformer with a
      single beta-turn and a gamma-bend for the L-Phe analog. On the other hand, a
      conformation with two fused beta-turns around the two tetrads His2-D-Phe3-Arg4
      Trp5 and Trp5-Gly6-Gly1-His2 dominates the equilibrium mixture for the D-Phe
      analog. For the D-Phe analog, the experimentally observed average conformation is
      corroborated by molecular dynamics simulations as well as by studies in
      cryoprotective solvent.

PMID- 9560001
TI  - Crystal and molecular structure of L-histidyl-L-serine trihydrate: occurrence of
      C(alpha)-H...O=C hydrogen bond motif similar to the motif in collagen triple
      helix and beta-sheets.
AB  - L-Histidyl-L-serine (HSN) trihydrate, C9H14N4O4-H2O, crystallizes in the
      orthorhombic space group P2(1)2(1)2(1) with a = 4.865(4), b = 15.604(4), c =
      18.918(5) and Z = 4. The crystal structure was solved by direct methods and
      refined to R1 = 0.070 by a full-matrix least-squares method. The peptide exists
      in a zwitterionic form, with the N-terminus in a protonated form and the C
      terminus in an ionized form. The imidazole ring of histidine in its neutral
      His(epsilon) tautomeric state has conformational angles chi(1)2 of -53.5(7)
      degrees and chi(21)1 of -55.4(8) degrees and the serine hydroxyl group has
      chi(1)2 of 68.2(7) degrees. The conformational angles deviate significantly from
      those of the dipeptide complexed with glycyl-L-glutamic acid in which the
      histidine is protonated. A noteworthy feature of the crystal packing is the
      occurrence of a C(alpha)-H O=C hydrogen bond motif similar to that observed in
      collagen triple helix and beta-sheets.

PMID- 9560002
TI  - The design, synthesis and activity of pentapeptide pp60c-src inhibitors
      containing L-phosphotyrosine mimics.
AB  - Efficient syntheses of 4-(R,S-hydroxyphosphonomethyl)-L-phenylalanine and 4
      carboxy-L-phenylalanine within the context of the pentapeptide Ac-Ile-X-Gly-Glu
      Phe-NH2 (wherein X = the unnatural amino acid) illustrate the use of a divergent
      synthetic strategy from an advanced common peptide intermediate to more readily
      access peptide-based tyrosine kinase inhibitors. The key intermediate, Ac-Ile
      Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2, was synthesized by a facile palladium
      catalyzed carbonylation of Ac-Ile-Phe(4-iodo)-Gly-Glu(O-tBu)-Phe-NH2. Oxidation
      of Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2 with tetrabutylammonium
      permanganate or addition of di-t-butylphosphite, both followed by trifluoroacetic
      acid deprotection, gave the target pentapeptide inhibitors wherein X = 4-carboxy
      L-phenylalanine or 4-(R,S-hydroxyphosphonomethyl)-L-phenylalanine, respectively.
      These two peptides gave somewhat more potent inhibition of the tyrosine kinase
      pp60c-src than the corresponding pentapeptide wherein X = L-phenylalanine,
      demonstrating that appended functionalities at the 4-position are accepted and
      can enhance binding through added interactions within the catalytic region of the
      active site.

PMID- 9560003
TI  - Peptides derived from human C-reactive protein inhibit the enzymatic activities
      of human leukocyte elastase and cathepsin G: use of overlapping peptide sequences
      to identify a unique inhibitor.
AB  - Ten overlapping 15-mer peptides, spanning the entire inner disulfide loop of
      human C-reactive protein (residues 36-97), were used to isolate a potent
      inhibitor of the enzymes human leukocyte elastase and human leukocyte cathepsin
      G, which are associated with chronic inflammatory tissue damage. In contrast to
      the inability of intact C-reactive protein to inhibit both enzymes, the synthetic
      peptide E62ILIFWSKDIGYSFT76 inhibited leukocyte elastase (Ki = 0.18 microM) and
      cathepsin G (Ki = 0.25 microM) at concentrations far lower than the acute-phase
      concentration of C-reactive protein. Several peptide-enzyme binding motifs were
      elucidated by structure-function studies, with the Glu62 residue being crucial in
      establishing long-range subsite interactions. Peptides derived from C-reactive
      protein, which may be generated in vivo by neutrophil-mediated proteolysis as
      part of a complex regulatory homeostatic mechanism, may play an important role in
      regulating the activity of matrix-degrading enzymes, specifically at sites of
      inflammation. The present results thus may shed additional insight on the
      physiological functions of the major acute-phase reactant C-reactive protein, and
      perhaps be used as a basis for the design of novel therapeutic substances.

PMID- 9560004
TI  - Preparations of Boc-Cys(S-Pyr)-OH and Z-Cys(S-Pyr)-OH and their applications in
      orthogonal coupling of unprotected peptide segments.
AB  - Boc-Cys(S-Pyr)-OH and Z-Cys(S-Pyr)-OH were prepared by addition of their cysteine
      derivatives to 3 equiv of 2,2'-dipyridyldisulfide in one portion. 2
      Mercaptopyridine was removed by addition of 0.1 M Cu(NO3)2 to the solution. Both
      derivatives are white solids and can be used to facilitate the formations of
      heterodisulfide bonds. Two methods of synthesizing peptides with N-terminal Cys(S
      Pyr) were also provided. Two peptide thiocarboxylic acids H-Tyr-Ser-Ala-Glu-Leu
      Val-SH and H-Tyr-Ser-Ala-Glu-Leu-Gly-SH were prepared on the thioester benzhydryl
      resin with the cleavage condition of 1.0 M TFMSA/TFA instead of HF. From the
      orthogonal couplings of these peptides with H-Cys(S-Pyr)-Tyr-Ser-Glu-Leu-Ala-NH2,
      both intramolecular acyl transfers finished at pH 7 at about 15 to 20 min. The
      intermediate acyl disulfide peptide was collected by high-performance liquid
      chromatography and identified by liquid chromatography-mass spectrometry.

PMID- 9560005
TI  - Self-assembling bis-dendritic peptides: design, synthesis and characterization of
      oxalyl-linked bis-glutamyl peptides [Glu(n)(CO2Me)n + 1-CO-]2; n = 1,3,7.
AB  - Three generations of glutamic acid dendrons [Glu(n),(CO2Me)n + 1; n = 1, 3, 7]
      have been joined together head-to-head by an oxalyl unit to form highly
      sterically congested bis-Glu-dendritic peptides with gelling properties. The
      single crystal X-ray structure of the first generation bis-dendritic peptide
      showed an extended hydrogen-bonded chiral tape with modest nonlinear optical
      activity.

PMID- 9560006
TI  - Chemical ligation of unprotected peptides directly from a solid support.
AB  - In this article we describe a new, convenient procedure to carry out
      intramolecular (cyclization) and intermolecular native chemical ligations of
      unprotected peptides directly from a solid support. Our solid-phase ligation
      approach eliminates the need to manipulate peptide (alpha)thioacid and peptide
      (alpha)thioester intermediates in aqueous solution before the ligation step,
      thereby leading to a reduction in handling losses and significantly increasing
      the overall efficiency of the chemical ligation strategy. A key step in our
      ligation scheme is the ability to generate fully unprotected peptides tethered to
      a solid support through an (alpha)thioester linkage. This can be achieved
      efficiently using optimized Boc-solid-phase peptide synthesis on a 3
      mercaptopropionamide-polyethylene glycol-poly-(N,N-dimethylacrylamide) copolymer
      support (HS-PEGA). Once the synthesis is complete, the fully protected peptide
      (alpha)thioester resin is treated with HF to give the corresponding fully
      unprotected peptide (alpha)thioester resin. Using this procedure several
      polypeptides ranging from 15 to 47 residues were synthesized successfully. These
      peptide-resins were then used to perform both intramolecular (head-to-tail
      cyclizations) and intermolecular solid-phase ligations. The intramolecular solid
      phase ligations proceeded much faster than their intermolecular counterparts, but
      in both cases the reactions were observed to be remarkably clean. The presence of
      aromatic thiol cofactors significantly accelerated the relatively slow
      intermolecular ligations. This novel methodology was then extended to provide a
      general method for performing sequential intermolecular ligations, allowing easy
      access to much larger polypeptide and protein systems.

PMID- 9560007
TI  - Three-dimensional structure of the Y1 receptor agonist [Leu31, Pro34]NPY as
      determined by NMR and molecular modeling.
AB  - The solution structure of the Y1 receptor agonist, porcine [Leu31, Pro34]NPY, has
      been investigated by two-dimensional NMR and molecular modeling. A complete
      assignment of the NMR resonances was achieved and 201 inter-residue nuclear
      Overhauser enhancement spectroscopy (NOESY) connectivities could be identified,
      comprising several connectivities between the N- and C-terminal segments. A
      molecular model was calculated by distance geometry, simulated annealing and
      conjugate gradients energy minimization using the NOE constraints. The results
      indicate that, like NPY and other peptides of the family, [Leu31, Pro34]NPY
      adopts a folded hairpin structure with the terminal segments in close proximity.
      Analysis of the secondary chemical shifts for the CH(alpha)'s and of the
      temperature dependence of the NH chemical shifts combined with the NOE
      constraints indicates a tendency toward helix structure for the segment 18-30 and
      the presence of turn structure for the C-terminal segment (residues 31-36).
      Native NPY and [Leu31, Pro34]NPY have most of their structures in common but
      differ slightly in their C-terminal portion. Based on the structures of NPY and
      of its specific agonists, [Leu31, Pro34]NPY and NPY 13-36, conclusions can be
      drawn about the structural requirements for binding to the Y1 and Y2 receptor
      subtypes.

PMID- 9560008
TI  - Neurotrophins and neuronal versus glial differentiation in medulloblastomas and
      other pediatric brain tumors.
AB  - Medulloblastomas are highly malignant and poorly understood childhood neoplasms.
      To determine if neurotrophins might influence the phenotypic properties of
      medulloblastoma in a paracrine or autocrine manner, 51 pediatric brain tumors
      including 20 biopsy specimens of these primitive neuroectodermal tumors (PNETs)
      and 31 other pediatric brain tumors were studied. Immunohistochemistry was used
      with antibodies to nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF), and NT-3, their cognate high affinity receptors as well as to neuronal
      and glial markers. TrkA, TrkB, and TrkC were observed in 5 (25%), 8 (40%), and 17
      (85%), respectively, of these medulloblastomas while NGF, BDNF, and NT-3 were
      observed in 6 (30%), 8 (40%), and 3 (15%), respectively, and antibodies to
      neurofilament (NF) and glial fibrillary acidic proteins (GFAP) stained 16 (80%)
      and 11 (55%), respectively. TrkA and NGF were not observed in the same biopsy
      samples, while TrkB and BDNF were co-distributed in 6 of the cases, all of which
      expressed NF proteins. TrkC and NT-3 were co-distributed in 3 of the
      medulloblastomas, and these areas overlapped with NF protein-positive tumor cells
      in all 3 cases. In contrast to medulloblastomas, TrkA and NGF co-distributed in
      other pediatric brain tumors, and both Trk receptors and their neurotrophins co
      distributed with GFAP-positive tumor cells in 13 (42%) of the non-PNET pediatric
      brain tumors. The absence of medulloblastomas that contain NGF and TrkA is
      consistent with in vitro data demonstrating that NGF-mediated TrkA signaling
      induces apoptosis. Finally, this study also suggests that BDNF and NT-3 may act
      in a paracrine or autocrine manner through TrkB and TrkC receptors, respectively,
      to induce neuronal differentiation in medulloblastomas.

PMID- 9560009
TI  - Autosomal dominant cerebellar ataxia (SCA6): clinical, genetic and
      neuropathological study in a family.
AB  - We describe a family with dominantly inherited ataxia of late adult onset.
      Expansion of a CAG repeat in the gene encoding the alpha1A voltage-dependent
      calcium channel was identified at autopsy in one patient, a 65-year-old woman
      with a disease duration of 11 years. In this patient, pathological changes were
      confined to the cerebellar cortex and inferior olivary complex. The cerebellar
      cortex showed severe loss of Purkinje cells with proliferation of Bergmann's
      glia, being more pronounced in the superior parts of the vermis and hemispheres.
      In the inferior olivary complex, a reduced neuronal cell population, which could
      be interpreted as a change secondary to the cerebellar cortical lesion, was
      evident. We conclude that the pathological phenotype of this newly classified
      autosomal dominant cerebellar ataxia, SCA6, is cerebello-olivary atrophy, or more
      strictly cerebellar cortical atrophy.

PMID- 9560010
TI  - Inducible nitric oxide synthase (iNOS)-like immunoreactivity in argyrophilic, tau
      positive astrocytes in progressive supranuclear palsy.
AB  - The immunoreactivity to the free radical-related enzymes, nitric oxide synthase
      (NOS) and superoxide dismutase (SOD), was examined in brain tissue in progressive
      supranuclear palsy (PSP). To determine the relationship between the
      immunoexpression of these enzymes and tau-positive, argyrophilic cytoplasmic
      inclusions, which are constantly present in PSP brains, double-label
      immunohistochemistry was applied. We demonstrated for the first time that strong
      inducible NOS-like immunoreactivity (iNOS-ir) was detected in tau-positive
      astrocytes that bore tufts of abnormal fibers (TAF), but not in oligodendrocytes
      containing argyrophilic/tau-positive coiled bodies nor in microglia. No brain NOS
      ir was detected in neurons with neurofibrillary tangles. MnSOD-ir was also
      detected in tau-positive astrocytes and oligodendrocytes. Nitrotyrosine-ir of
      variable intensity was observed in astrocytes, oligodendrocytes and neurons. Our
      results indicate: (1) that TAF-bearing astrocytes may be a major source of
      excessive NO in PSP brains; (2) that after the induction of iNOS by unknown
      stimulating factors, TAF-bearing astrocytes produce an excessive amount of NO
      that exceeds the detoxification capability of SOD; and (3) that peroxynitrite and
      excessive NO, both cytotoxic, may be present in astrocytes, oligodendrocytes and
      neurons. Although the precise relationship between NO production and neuronal
      cell death in PSP remained uncertain, based on the specificity of TAF for PSP
      brains, our results indicated a possible mechanism of NO-mediated cytotoxicity
      that may contribute to the neuronal and glial cell damage followed by abnormal
      tau accumulation in this disease.

PMID- 9560011
TI  - Immunohistochemical examination of c-Met protein expression in astrocytic tumors.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF), which has various physiological
      functions, and its receptor c-Met, the human c-met proto-oncogene product, are
      thought to be determinant in the pathological processes of various malignancies.
      To investigate the possible role of HGF/SF in the progression of development of
      astrocytic tumors, we examined the expression of c-Met in these tumors.
      Immunohistochemistry using the streptavidin-biotin peroxidase complex method and
      immunofluorescence double staining with anti-c-Met polyclonal and anti-glial
      fibrillary acidic protein monoclonal antibodies were performed. Positive c-Met
      expression was detected in 31 of the 42 astrocytic tumors and some of the control
      cases analyzed. c-Met-positive cells showed morphological characteristics of
      astrocytes. Especially in the cases of high-grade tumors, c-Met positivity was
      abundant in cells in both vascular-rich and peripheral regions of the tumors but
      not in the cells with distinctly malignant features. Immunofluorescence double
      staining revealed that the c-Met-positive cells were in part of astrocytic
      origin. We suggest that c-Met-positive cells are affected by some factors in the
      lesions where the pathological processes are in a state of development. Our
      studies indicated that c-Met expression might take part in glioma invasion but
      not in the development of malignancy.

PMID- 9560012
TI  - Structural changes in male trapezius muscle with work-related myalgia.
AB  - Muscular changes in male forest machine operators with work-related neck and
      shoulder myalgia were studied. Enzyme cyto- and immunohistochemical analysis was
      carried on muscle biopsies obtained from ten myalgic subjects (M), nine non
      myalgic selected in the same work place (NM) and six healthy young men (C). The M
      group displayed a significant increase in type IIA fibres in comparison to the C
      group. This hypertrophy was accompanied by a parallel increase in the capillary
      bed. Both the M and NM groups exhibited an increase in fibres with a disorganised
      mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase
      occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a
      mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were
      also more frequent in the M group. These changes are probably related to injury
      regeneration cycles. These data support the association between the work
      conditions and muscle changes in work-related trapezius myalgia.

PMID- 9560013
TI  - Tick-borne encephalitis in dogs: neuropathological findings and distribution of
      antigen.
AB  - Eight dogs originating from different regions of Austria [all of them known as
      tick-borne encephalitis (TBE) areas] with severe neurological signs were either
      euthanatized or died spontaneously. Tick-borne encephalitis virus (TBEV) antigen
      was detected in the brains of five of these dogs by immunohistology, but not in
      the others. All of the dogs, however, had identical neuropathological changes.
      There were moderate lymphohistiocytic meningitis, widespread neuronal necroses,
      karyorrhexis of glial cells, numerous neuronophagic nodules, and extensive
      microgliosis. In the cerebellum, loss of Purkinje cells and proliferation of
      microglial cells in the molecular layer were found. All brain regions showed
      numerous perivascular cuffs consisting of lymphocytes, macrophages, plasma cells
      and, occasionally, red blood cells. The blood-derived cells were not restricted
      to the perivascular spaces but diffusely infiltrated the neuropil. The most
      severe changes were localized in the neuroparenchyma surrounding the fourth
      ventricle. Lesions were less severe in basal ganglia, thalamus, mesencephalon,
      nuclei of pons and medulla oblongata. Moderate lesions were found in the gray
      matter of neocortex and allocortex, hippocampus and molecular and Purkinje cell
      layers of the cerebellum. White matter was slightly to moderately affected. The
      choroid plexus was free of inflammation. Due to rapid virus clearance mechanisms
      in this disease, antigen was not detectable in all cases. Neuropathological
      changes identical with those of immunohistologically proven cases justified the
      diagnosis TBE in these cases. In addition, the neuropathological diagnosis was
      supported by the origin of the affected dogs from endemic areas, the seasonal
      occurrence of the disease and a clinical history of a highly febrile neurological
      disease with short duration.

PMID- 9560014
TI  - Characterizations of heterotopic neurons in the spinal cord of amyotrophic
      lateral sclerosis patients.
AB  - This report concerns a comparative immunocytochemical, ultrastructural and
      morphometric investigation on heterotopic neurons in the white matter of the
      spinal cords of 19 patients with amyotrophic lateral sclerosis (ALS) and 18 age
      matched neurologically normal individuals. The study revealed that the
      heterotopic neurons were scattered in the white matter, often adjacent to gray
      matter, that they immunoreacted with the antibody to synaptophysin, and that
      there were synaptic apparatuses on the surface of their somata and their neuronal
      processes. Bunina bodies and ubiquitin-positive inclusions such as Lewy body-like
      inclusions and skein-like inclusions, characteristic of anterior horn neurons of
      ALS, were present in the cytoplasm of the patients' heterotopic neurons in the
      anterior or lateral column of the white matter. These findings suggest that
      heterotopic neurons in the anterior or lateral column have the characteristics of
      alpha motor neurons. The average number of heterotopic neurons observed in ALS
      patients was generally less than in normal subjects. This reduction was
      correlated with the severity of neuronal loss. The heterotopic neurons in ALS
      were less susceptible to the degenerative process as compared with spinal cord
      anterior horn cells. We assume that in this disease the heterotopic neurons may
      be degenerated and their number diminished after or concomitantly with the
      depletion of anterior horn neurons.

PMID- 9560015
TI  - Identification of macrophage populations expressing tumor necrosis factor-alpha
      mRNA in acute multiple sclerosis.
AB  - Macrophages are involved in central nervous system (CNS) demyelination in
      multiple sclerosis (MS) and other demyelinating diseases. Macrophages seen in MS
      lesions form a heterogeneous population with respect to their stage of activation
      and differentiation. We have analyzed macrophages from active demyelinating
      lesions of a patient who died from fulminant MS of Marburg's type to define the
      functional heterogeneity of different macrophage populations in acute
      demyelination. We examined tumor necrosis factor-alpha (TNF-alpha) mRNA
      expression in macrophages defined by different activation markers. The majority
      of TNF-alpha mRNA-positive cells were macrophages positive for the pan-macrophage
      marker KiM1P. A subgroup of TNF-alpha mRNA-positive macrophages was stained by
      the early activation marker MRP14. In contrast, macrophages positive for the
      acute activation marker 27E10 were entirely negative for TNF-alpha mRNA. In
      conclusion, macrophages in acute demyelinating CNS lesions are heterogeneous as
      shown by staining for different activation markers. This heterogeneity is also of
      functional relevance as certain subpopulations are involved in TNF-alpha mRNA
      expression, while others are not. This may be important for directing therapeutic
      strategies against well-defined pathogenic macrophage populations.

PMID- 9560016
TI  - Distribution of B-50(GAP-43) mRNA and protein in the normal adult human spinal
      cord.
AB  - B-50(GAP-43) is a phosphoprotein mainly found in the nervous system which plays a
      major role in neurite growth during development and regeneration as well as in
      synaptic remodelling. In the mature intact central nervous system, intense B-50
      immunoreactivity (B-50-IR) can still be detected in regions which maintain
      residual capacity for structural re-organization. B-50 expression has been
      studied extensively in laboratory animals; however, its distribution and
      regulation in the human spinal cord is largely unknown. As a first step to
      analyze lesion-induced structural alterations, we investigated the distribution
      of B-50 protein and mRNA in the normal adult human spinal cord and dorsal root
      ganglia. Intense B-50-IR was localized to the superficial laminae of the dorsal
      horn at all segmental levels, the intermediolateral nucleus at thoracic levels
      and Onuf's nucleus at sacral levels. Scattered neurons, particularly in the
      ventral horn of lumbar and sacral segmental levels (and occasionally also in
      Clarke's nucleus) displayed intense B-50-IR in close apposition to the perikaryal
      and proximal dendritic surfaces. Nonradioactive in situ hybridization indicated
      that B-50 mRNA could also be detected in neurons of the ventral horn and also in
      the intermediolateral nucleus. The distribution of B-50 mRNA and protein in the
      normal human spinal cord shows a marked similarity to that reported in
      experimental animals, including the selective labelling of Onuf's nucleus.
      However, the strong B-50-IR on the surface of some large anterior horn motor
      neurons has not been observed in other mammals. This finding might reflect a
      particular state of readiness for synaptic plasticity.

PMID- 9560017
TI  - Possible neuroprotective role of clusterin in Alzheimer's disease: a quantitative
      immunocytochemical study.
AB  - Clusterin is a secreted glycoprotein that is expressed in response to tissue
      injury both in peripheral organs and in the brain. Recent studies have shown a
      substantial increase in clusterin mRNA in pyramidal neurons of the hippocampus
      and the entorhinal cortex in Alzheimer's disease (AD), with clusterin
      immunoreactivity occurring in neuropil threads, neurofibrillary tangles (NFT),
      and senile plaques. To elucidate further the role of this protein in the
      degenerative process, a quantitative study of its distribution in the cerebral
      cortex of non-demented and AD patients, all older than 85 years of age, was
      performed using immunocytochemistry. Using a stereological approach, we found
      that in cortical areas affected in AD, such as the entorhinal, inferior temporal
      and superior frontal cortices, the percentage of NFT-free neurons displaying
      clusterin immunoreactivity was significantly higher than that in non-demented
      cases. No such increase in the density of clusterin-immunoreactive neurons was
      seen in cortical areas that were less affected in the disease process.
      Furthermore, clusterin immunoreactivity was rarely observed in NFT-containing
      neurons. In conjunction with previous observations in peripheral tissues, these
      data suggest that clusterin may have a neuroprotective role, and that in AD, low
      cellular expression of this protein may be associated with neuronal degeneration
      and death.

PMID- 9560018
TI  - Cytoarchitectonic alterations in the supramarginal gyrus of late onset
      Alzheimer's disease.
AB  - The intellectual status of 28 women of over 75 years of age had been
      prospectively assessed by the Blessed test score. It ranged from nearly normal to
      deeply altered by dementia. After autopsy, the supramarginal gyrus was marked at
      the surface of the brain. Sections, 1 cm thick, were cut with a specially devised
      macrotome. The volume of the parietal lobe was measured by a point counting
      method, using Cavalieri principle. A sample from the supramarginal gyrus was
      taken from the previously marked area and the shrinkage due to the histological
      procedures was measured (it averaged 12%). More than 500 nucleolated neuronal
      profiles per case were mapped with a semi-automatic system. Density maps of the
      neuronal profiles were drawn and mean density was calculated using Dirichlet
      tessellation. The thickness of the cortical ribbon was standardized on the maps.
      The density of the neurons per unit volume was calculated, taking into account
      the section thickness measured for each sample with a length gauge fastened to
      the Z axis of the microscope. Statistical correlations were sought between the
      mean and laminar densities of the neurons on one hand, and Blessed test score,
      the densities of neurofibrillary tangles (NFT) and of senile plaques profiles, on
      the other hand. Finally, the total number of neurons present in the parietal lobe
      was estimated in each case. Neuronal loss appeared to be linked with the density
      of the NFT (r = -0.52; P < 0.004). The correlation was mainly due to a severe
      drop in neuronal number observed in the cases with more than 5 NFT/mm2. An
      average difference of 98 x 10(6) neurons per parietal lobe was found between the
      cases with less than 5 NFT/mm2 and those with more. The neuronal loss
      predominated in layers II and III (upper part). A multivariate analysis showed
      that the intellectual status was better correlated with the density of the
      tangles than with the neuronal loss.

PMID- 9560020
TI  - Laminar spongiosis of the dentate gyrus: a sign of disconnection, present in
      cases of severe Alzheimer's disease.
AB  - An extensive laminar spongiosis was found in the outer part of the dentate gyrus
      in an 84-year-old patient. An old cavitary infarct in the parahippocampal gyrus
      disconnected the dentate gyrus from the entorhinal area. This finding prompted us
      to seek laminar spongiosis in Alzheimer's disease, where the neuronal loss in the
      entorhinal cortex might be severe. The dentate gyrus was systematically examined
      in a series of prospectively assessed cases either intellectually normal or
      affected by mental impairment of graded severity. Laminar spongiosis was present
      in the most severely affected patients. The neuritic crown of the senile plaques
      seen in the laminar band of spongiosis contained only a few tau- and Bodian
      positive fibers, a sign that was taken as evidence of "plaque denervation". By
      contrast, deposits of Abeta peptide remained abundant but lacked a dense core.
      These data suggest that dendritic and axonal processes are intermingled in the
      senile plaque and that the amyloid core is at least partially dependent on the
      presence of the axonal component.

PMID- 9560019
TI  - Bcl-2 and Bax protein expression in Alzheimer's disease.
AB  - Beta-amyloid deposition and neurofibrillary degeneration are important
      pathological findings in the brains of patients with Alzheimer's disease (AD). In
      the present study, we have examined Bcl-2 and Bax immunoreactivity in the
      hippocampus of AD cases, with special attention to the possible relationship
      between Bcl-2 and Bax immunoreactivity, and neurofibrillary degeneration and
      senile plaques. Different antibodies were used, including Bcl-2 (N-19), Bcl-2
      (BioGenex), Bax (P-19) and Bax (N-20), and their specificity was tested on
      Western blots of brain homogenates. No differences between Bcl-2 and Bax
      immunoreactivity in tangle-bearing and non-tangle-bearing neurons were observed,
      thus suggesting that Bcl-2 and Bax do not participate in tangle formation.
      Overexpression of Bcl-2 protein in reactive glial cells surrounding senile
      plaques suggests that Bcl-2 may play a role in the survival of reactive glia. On
      the other hand, overexpression of Bax immunoreactivity in dystrophic neurites of
      senile plaques suggests that Bax is associated with neurite degeneration in
      senile plaques. Finally, Bax (P-19), but not Bax (N-20), immunoreactivity was
      localized in amyloid fibrils of senile plaques. Since Western blots to Bax (P-19)
      recognize multiple bands in addition to the expected band of about 21 kDa, it is
      suggested that Bax (P-19) immunoreactivity of amyloid fibrils is not specific.

PMID- 9560021
TI  - Lipidized (foamy) tumor cells in a spinal cord ependymoma with collagenous
      metaplasia.
AB  - We report a 49-year-old woman with a spinal cord ependymoma located in the
      thoracolumbar region. At surgery, a soft dark-grayish tumor, which contained a
      hard whitish area, was removed. The specimen was a moderately cellular tumor with
      a central core made up of collagen nodules poor in cellular elements. Many of the
      tumor cells possessed ground glass-like eosinophilic cytoplasm, and frequently
      foamy tumor cells were evident. Perivascular pseudorosettes, ependymal rosettes
      and canals were present, the latter being rare. Many tumor cells, including those
      with foamy cytoplasm, were positive for glial fibrillary acidic protein. Similar
      tumor cells were also seen among, and even within, the collagen nodules. The MIB
      1 labeling index was 0.66%. Ultrastructurally, the frequent lipidized tumor cells
      were ependymal in nature; cytoplasmic 10-nm-wide filaments, and intracytoplasmic
      lumina and intercellular microrosettes lined by microvilli were evident. Cilia
      were very rare. We considered the present case to be an unusual, lipidized
      variant of ependymoma. The collagen nodules appeared to be produced by the tumor
      cells themselves.

PMID- 9560022
TI  - Sporadic motor neuron disease with severe sensory neuronopathy.
AB  - We report a 62-year-old man with sporadic motor neuron disease (MND) of 52
      months' duration with progressive sensory disturbance and high cerebrospinal
      fluid protein content. Neuropathologically, both the upper and lower motor neuron
      systems were severely affected, and light and electron microscopy revealed Bunina
      bodies and skein-like inclusions, which are characteristic of amyotrophic lateral
      sclerosis, in the remaining anterior horn cells. Moreover, there was severe
      degeneration without inflammatory infiltrates in the spinal posterior columns,
      spinal ganglia, and peripheral sensory nerves. These findings suggest that this
      case may be an unusual variant of sporadic MND with severe somatic sensory system
      involvement.

PMID- 9560023
TI  - Megalencephaly, hydrocephalus and cortical dysplasia in severe dwarfism mimicking
      leprechaunism.
AB  - This report concerns an autopsy case of megalencephaly exhibiting a unique
      combination of physical and brain malformations. A 4-year-old boy had a peculiar
      face, a severe reduction of subcutaneous adipose tissue, severe growth failure
      and frequent hypoglycemic episodes. These clinical features were compatible with
      leprechaunism; however, the absence of hyperinsulinemia and insulin resistance
      prevented the diagnosis of leprechaunism. The autopsy disclosed complex cardiac
      and brain malformations. Although hydrocephalus coexisted, the brain weight after
      complete removal of the cerebrospinal fluid was 2260 g, which was greater than
      the average brain weight of normal Japanese children of the same age. The
      neuronal density in the cerebral cortex was decreased, while the surface area of
      the cerebral cortex and white matter were greater than those in an age-matched
      control. There was cortical dysplasia in the frontal and parietal lobes.
      Endocrine tests and immunohistochemical analysis of the brain did not demonstrate
      any abnormalities in the hypothalamus-pituitary system. Megalencephaly can be
      associated with dwarfism, and this case is important for consideration of the
      interrelationship between neuronal proliferation and physical growth.

PMID- 9560024
TI  - Sarcoid neuromyopathy with selective involvement of the intramuscular nerves.
AB  - A 35-year-old man affected with pulmonary sarcoidosis had a 12-year history of
      fatigue and pain in the limbs, with normal neurological examination, except for
      diffusely absent deep tendon reflexes. Muscle biopsy samples showed multiple
      noncaseating granulomas, most prominent around the intramuscular nerves, with
      predominance of CD4+ cells. Intramuscular nerve bundles surrounded by granulomas
      were immunolabelled with laminin alpha1, alpha2, beta1 and gamma1 chain, and
      collagen IV. Sural nerve biopsy samples were normal. This patient showed a unique
      histopathological pattern of sarcoid neuromyopathy characterized by distribution
      of granulomas or infiltrating cells around intramuscular nerve fibers. The
      clinical picture, restricted to nonspecific symptoms of fatigue and myalgia, and
      loss of deep tendon reflexes, correlated well with the selective localization of
      sarcoid lesions in contiguity with the intramuscular nerves. To our knowledge,
      this peculiar clinico-pathological correlation has not been reported previously.

PMID- 9560025
TI  - Quality of general movements in preterm infants with transient periventricular
      echodensities: a commentary.

PMID- 9560026
TI  - Adrenomedullin: its role in perinatal adaptation.

PMID- 9560027
TI  - Risk factors for impaired length growth in early life viewed in terms of the
      infancy-childhood-puberty (ICP) growth model.
AB  - A difference in length or height growth is observed between populations in
      developing and developed countries and, within a country, between well-off and
      poor subpopulations. The aim of this community-based study was to identify
      possible risk factors for growth stunting in early life using the infancy
      childhood-puberty (ICP) growth model. A periurban slum, a village and an urban
      slum, plus a local control group in Lahore, Pakistan, were investigated. In
      total, there were 425 infants born from September 1984 to March 1987 in the
      study. Children were followed from birth to 24 months and anthropometric data
      were recorded at each examination. A well-designed questionnaire was used to
      collect background information to identify risk factors for growth faltering over
      this period. The age at onset of the childhood component was determined
      individually using the ICP growth model. A late onset was defined as onset after
      12 months. Univariate odds ratio analysis identified 20 significant risk factors
      for a delayed childhood onset in the total sample. Backward logistical analysis
      showed that only six variables were significant, i.e. small number of rooms in a
      household, episode(s) of diarrhoeal diseases, poor house structure, low body mass
      index, early end of breastfeeding and birth in warm season. Stratified analysis
      showed that episode(s) of diarrhoeal diseases and birth in warm season were the
      only significant risk factors in the two poor areas. This study also found that
      the impact of diarrhoeal diseases on length growth persisted after allowing for
      birth season. Seasonal variation in length growth was seen in the age at onset of
      the childhood component. General socioeconomic status was found to be a risk
      factor for growth faltering in early life. Diarrhoeal diseases and being born in
      a warm season are particular risk factors for growth faltering in early life.

PMID- 9560028
TI  - Measured and predicted bone mineral content in healthy boys and girls aged 6-18
      years: adjustment for body size and puberty.
AB  - Dual-energy X-ray absorptiometry (DEXA) is a rapid and precise technique for the
      assessment of bone mineralization in children. Interpretation of the results in
      growing children is complex as results are influenced by age, body size (height
      and weight) and puberty. Conventionally, bone mineral data derived from DEXA have
      been presented as an areal density [BMD; bone mineral content (BMC, g)/projected
      bone area (BA, cm2)], yet this fails to account for changes in BMC that result
      from changes in age, body size or pubertal development. Measurement of BMC and BA
      of the whole body, lumbar spine and left hip were made in 58 healthy boys and
      girls using DEXA. The relationship between BMC and BA was curvilinear, with the
      best fit being that of a power model (BMD = BMC/BAlambda, where lambda is the
      exponent to which BA is raised in order to remove its influence on BMC). The
      value of lambda changed when measures of body size and puberty were taken into
      account (e.g. for lumbar spine from 1.66 to 1.49). Predictive formulae for BMC
      were produced using regression analysis and based on the variables of age, body
      size and pubertal development. This provides a method for interpreting the
      measured BMC which is independent of such variables and a constant reference
      range for children aged 6-18 y.

PMID- 9560029
TI  - Early childhood feeding practices in southern Italy: is the Mediterranean diet
      becoming obsolete? Study of 450 children aged 6-32 months in Campania, Italy.
      Cultural Paediatric Association.
AB  - With increasing affluence, the traditional food choices of Mediterranean
      populations are changing. The changes appear to begin in early infancy, with
      increased consumption of processed foods. To determine current consumption
      patterns of the diets of 450 toddlers, 6-32 months old, enrolled from 17
      paediatric practices in the Campania region of Italy, quantitative data were
      collected for 7 d, using calibrated feeding bottles, cups and dishes. Automated
      food analysis was employed and quality control was performed on a sub-sample. The
      average daily intake was 373 kJ/kg. Forty-three percent of energy was provided by
      carbohydrates, while fats supplied 39%, 45% of fats were saturated and 46.7% were
      monosaturated (primarily olive oil). Proteins provided 18% of daily energy; most
      (81.4%) were of animal origin. Fibre was virtually absent from the study
      children's diet. Total daily cholesterol reached an average value of 191 mg/d,
      corresponding to 201 mg/4.2 mJ. The intake per kg of cholesterol increased with
      age in the first year, while proteins and fats decreased. Dairy products were the
      main source of energy, fats and cholesterol. Vegetables and legumes were a minor
      source of energy at all ages: the consumption of fruit decreased with age.
      Although the overall pattern of feeding of this cohort remains favourable
      compared with other children groups in developed countries, consumption of whole
      milk and full fat dairy products may be reduced to equilibrate the diet.

PMID- 9560030
TI  - Growth hormone treatment of short children born small-for-gestational-age: the
      Nordic Multicentre Trial.
AB  - The aims of this study were to evaluate the efficacy and safety of different
      doses of growth hormone (GH) treatment in prepubertal short children born small
      for-gestational-age (SGA). Forty-eight children born SGA from Sweden, Finland,
      Denmark and Norway were randomly allocated to three groups: a control group of 12
      children received no treatment for 2 y, one group was treated with GH at 0.1
      IU/kg/d (n=16), and one group was treated with GH at 0.2 IU/kg/d (n=20). In total
      42 children completed 2 y of follow-up, and 24 children from the treated groups
      completed 3 y of treatment. Their mean (SD) age at the start of the study was
      4.69 (1.61) y and their mean (SD) height was -3.16 (0.70) standard deviation
      scores (SDS). The children remained prepubertal during the course of the study.
      No catch-up growth was observed in the untreated group, but a clear dose
      dependent growth response was found in the treated children. After the third year
      of treatment, the group receiving the higher dose of GH, achieved their target
      height. The major determinants of the growth response were the dose of GH used,
      the age at the start of treatment (the younger the child, the better the growth
      response) and the family-corrected individual height deficit (the higher the
      deficit, the better the growth response). Concentration of insulin-like growth
      factor-I (IGF-I) and IGF-binding protein-3 increased during treatment. An
      increase in insulin levels was found without negative effects on fasting glucose
      levels or glycosylated haemoglobin levels. GH treatment was well tolerated. In
      conclusion, short prepubertal children born SGA show a dose-dependent growth
      response to GH therapy, and their target height SDS can be achieved within 3 y of
      treatment given GH at 0.2 IU/kg/d. However, the long-term benefit of different
      regimens of GH treatment in children born SGA remains to be established.

PMID- 9560032
TI  - Chronic non-specific diarrhoea in childhood: how often is it iatrogenic?
AB  - Epidemiological data, the appropriateness of the medical approach, the
      effectiveness of unrestricted diet and the subsequent course of chronic non
      specific diarrhoea (CNSD) were evaluated in 20 children, mean age at diagnosis
      4.7 y, and mean duration of diarrhoea 24 months. A mean of 2.4 previous hospital
      admissions and a mean of 2.5 diagnoses other than CNSD were recorded per child
      before admission. On admission, 14/20 were following an elimination diet and 8/20
      had an inadequate caloric intake; 16/20 had a weight/height ratio below the 50th
      percentile. In all cases a normal diet prescribed during hospitalization improved
      the diarrhoea and increased weight. A telephone interview performed 5.6 y after
      discharge revealed that in 10/20 of the cases, the parents were disappointed with
      the unrestricted diet prescribed during hospitalization. Nevertheless they
      reported that CNSD stopped spontaneously in a mean time of 1.7 y.

PMID- 9560031
TI  - Rotaviral antibodies in the treatment of acute rotaviral gastroenteritis.
AB  - The efficacy of hyperimmune bovine colostrum received from cows immunized with
      simian rotavirus SA11 in the treatment of rotavirus gastroenteritis was compared
      in a randomized double-blind trial to colostrum and ordinary milk preparations.
      One hundred and thirty-five children aged 6-30 months with rotaviral
      gastroenteritis received either hyperimmune bovine colostrum (n=42), ordinary
      colostrum (n=42) or milk (n=41) as a 100 ml solution four times/d for 4 d. Even
      though the differences were in favour of hyperimmune bovine colostrum in all the
      variables evaluated [greater weight gain (403 vs 343 g), shorter duration of
      diarrhoea (3.1 vs 3.6 d), fewer stools during 6 d (11.5 vs 13.6) and fewer stools
      during the first 3 d (9.3 vs 11.3)], all the differences were statistically
      insignificant. Differences of this size are clinically unimportant in well
      nourished immunocompetent children, but we suggest that the hyperimmune bovine
      colostrum tested in our trial had some effects in the treatment of acute
      rotaviral gastroenteritis and should be evaluated further.

PMID- 9560033
TI  - Precipitants and aetiology of cyclic vomiting syndrome.
AB  - Thirty-two patients aged 2-22 y with cyclic vomiting syndrome (CVS), and 64 age-
      and gender-matched controls were assessed to determine the nature, severity,
      precipitants and associated features of attacks and the incidence of potential
      aetiological factors. The mean age of onset was 3.5 y. Patients experienced a
      mean of nine attacks per year, of average duration 2.4 d, and two-thirds missed
      more than 10 d of school per year. Patients were more likely to have migraine and
      co-ordination difficulties, a past history of forceps delivery and
      gastroesophageal reflux than controls. Compared with controls, subjects had a
      higher incidence of psychological symptoms (38% compared with 19%) and migraine
      (37% compared with 9%). CVS is a chronic, disabling condition and is a migraine
      variant, with attacks usually precipitated by stress and intercurrent infections.

PMID- 9560034
TI  - Essential fatty acid metabolism in infants with cholestasis.
AB  - Long-chain polyunsaturated fatty acids are important for the growth and early
      development of the central nervous system. Cholestatic infants suffer from fat
      malabsorption and disturbed lipid metabolism and therefore may be at risk of
      developing polyunsaturated fatty acid depletion. The aims of this study were to
      determine essential fatty acid status in cholestatic infants and to study the
      relationship to disease severity, degree of undernutrition, antioxidant status
      and mode of feeding. Twenty-four-hour dietary records were obtained in 34
      cholestatic infants, and measurements were taken of skin fold thicknesses,
      bilirubin levels, activities of serum alanine aminotransferase, alkaline
      phosphatase, gamma-glutamyl transpeptidase, prothrombin time, serum
      concentrations of albumin, bile acids, total lipids, phospholipids, cholesterol,
      vitamins A and E, the fatty acid composition of plasma phospholipids and plasma
      lipid peroxides expressed as thiobarbiturate reactive substance (TBARS). Plasma
      phospholipid fatty acids and TBARS were also determined in 12 age-matched healthy
      control infants. The cholestatic patients had very low percentage values of
      phospholipid essential fatty acids, particularly linoleic acid ( 18:2omega-6,
      median 14.74% vs 20.76% in controls, p < 0.001) and its major metabolite
      arachidonic acid (20:4omega-6, 6.80 vs 7.87%, p=0.04). The patients' essential
      fatty acid depletion was reflected by increased levels of the non-essential fatty
      acids, Mead acid (20:3omega-9, 0.74 vs 0.21%, p < 0.001) and palmitoleic acid
      (16:1omega-7, 2.20 vs 0.43%, p < 0.001). Polyunsaturated fatty acid profiles did
      not differ between infants with biliary atresia (n=13) and those with
      intrahepatic cholestasis (n=21), or between 17 infants with severe malnutrition
      (all skin folds < 10th percentile) and mild malnutrition (at least two skin folds
      > 10th percentile). TBARS were significantly higher in cholestatic patients than
      in controls (2.74 vs 0.85 nmol ml(-1), p < 0.001) and correlated with direct
      (r=0.41, p=0.02) and total bilirubin. The daily dietary intake of linoleic acid
      (per 100 kcal) correlated with plasma phospholipid linoleic acid (r=0.38,p=0.037)
      and total omega-6 fatty acids (r=0.38,p=0.036). Breastfed cholestatic infants
      (n=6) had higher values of the omega-3 long-chain polyunsaturated fatty acids
      docosapentanoic acid (22:5omega-3, 0.47 vs 0.28%, p=0.0006) and docosahexanoic
      acid (22:6omega-3, 2.39 vs 1.73%, p=0.01) than formula-fed infants, while disease
      severity was similar in the two groups. In conclusion, cholestatic infants are at
      high risk of essential fatty acid depletion, which appears to be related to fat
      malabsorption, hepatic essential fatty metabolism, enhanced lipid peroxidation
      and dietary intake.

PMID- 9560035
TI  - Sociodemographic risk factors for sudden infant death syndrome: associations with
      other risk factors. The Nordic Epidemiological SIDS Study.
AB  - The aim of this study was to investigate associations between sudden infant death
      syndrome (SIDS) and social factors in the Nordic countries. A case-control study
      was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS
      Study. Parents of 244 SIDS infants and 869 control infants matched on gender, age
      at death and place of birth filled in questionnaires. The dataset was analysed by
      conditional logistic regression. In univariate analysis, the following
      sociodemographic factors were associated with an increased risk of SIDS: low
      maternal age [odds ratio (OR) 7.8; 2.8-21.5], high birth order (OR 4.4; 2.5-7.5),
      single motherhood (OR 2.9; 1.7-5.0), low maternal education (OR 4.5; 2.8-7.1),
      low paternal education (OR 3.0; 1.9-4.7), maternal unemployment (OR 2.4; 1.8-3.4)
      and paternal unemployment (OR 4.0; 2.7-5.9). In a multivariate analysis where
      maternal smoking was also included, only paternal unemployment, young maternal
      age and high birth order remained significantly associated with SIDS. Housing
      conditions were not associated with SIDS. However, the risk of SIDS was high if
      the family had lived in their present home for only a few years (OR 2.3; 1.3
      4.1). Sociodemographic differences remain a major concern in SIDS in a low
      incidence situation and even in an affluent population with adequate health
      services.

PMID- 9560036
TI  - Mental retardation in Norway: prevalence and sub-classification in a cohort of
      30037 children born between 1980 and 1985.
AB  - OBJECTIVES: We wanted to determine the prevalence and subcategories of mental
      retardation (MR) defined as IQ < or = 70 in Akershus county, which rated by
      average yearly income, had the second highest socioeconomic status (SES) in
      Norway. METHODS: The study population consisted of 30 037 children born between
      1980 and 1985. Cases were ascertained from multiple sources and psychometrically
      assessed, predominantly with the Wechsler tests, which were standardized in
      Norway in 1978. The cases were divided into four groups: profound (IQ < 20),
      severe (IQ 20-34), moderate (IQ 35-49), and mild (IQ 50-70) MR, according to the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). The
      median age was 10.8 y. The frequency and degree of parental consanguinity were
      registered, and the average inbreeding coefficient was calculated. RESULTS:
      Altogether, 185 had IQ < or = 70, giving a prevalence of MR of 6.2/1000.
      Prevalences for profound, severe, moderate, and mild MR were 0.8, 0.4, 1.5 and
      3.5/1000, respectively. In two, possibly three, cases the parents were second
      cousins, giving an average inbreeding coefficient of 20-30 x 10(-5). CONCLUSIONS:
      The low prevalence of MR, particularly mild MR, could partly be explained by high
      SES, old standardization of IQ-test, and low inbreeding coefficient. The
      proportion of profound MR was considerably higher than estimated by DSM-IV.

PMID- 9560038
TI  - Risk factors for low birthweight in Japanese infants.
AB  - The purpose of our study was to identify risk factors for low birthweight (LBW;
      birthweight < 2500 g) in Japanese infants. The data was collected from
      questionnaires completed by the parents of 23132 infants who underwent a
      standardized well baby check-up for 1-month-old infants, conducted by the Fukuoka
      City Medical Association from 1987 to 1995. The following eight factors and their
      second-order interaction terms were examined as potential risk factors for LBW:
      maternal age at delivery, history of live-born LBW infant, history of abortion in
      previous pregnancies, maternal smoking, coffee and alcohol consumption during
      pregnancy, prenatal training and live birth order. The results of multiple
      logistic regression analysis showed that the following three factors and one
      interaction term significantly contributed to LBW: history of live born LBW
      infant, maternal smoking, live birth order and the interaction between maternal
      smoking and live birth order. The smoker-related risk for LBW was quite different
      in each of the three groups stratified by live birth order. Efforts should be
      made, for example, to increase the accessibility of early, high-quality prenatal
      care for the high-risk groups with previous LBW babies and to implement smoking
      intervention, ranging from specific medical procedures to broad-scale public
      health and health-related educational programs in schools.

PMID- 9560037
TI  - Acute effects on systemic circulation after intratracheal instillation of
      Curosurf or Survanta in surfactant-depleted newborn piglets.
AB  - Systemic vasodilatation in surfactant-depleted newborn piglets is induced by 200
      mg/kg of modified porcine lung surfactant (Curosurf). The aim of this
      investigation was to study whether this effect is dependent on dose and could
      further be induced by instillation of a bovine surfactant preparation (Survanta).
      Twenty-two 3-5-d old piglets were subjected to repeated saline lung lavage and
      then randomized to one of three groups. Instillation of either Curosurf l00 mg/kg
      (n=8), Survanta l00 mg/kg (n=7) or Curosurf 200 mg/kg (n=7) was performed through
      the endotracheal tube. Systemic vascular resistance decreased 7 (+/-4)%, 15 (+/
      12)% and 18 (+/-6)% in the three groups, respectively (p < 0.05 in all three
      groups). A significant difference between the high and low dose Curosurf groups
      was found (p < 0.05), whereas no significant difference was seen between the
      Curosurf 100 mg group and the Survanta group. The decrease in vascular resistance
      was compensated by an increase in cardiac output, resulting in a stable mean
      arterial blood pressure. In conclusion, both Curosurf and Survanta induce a
      significant decrease in systemic vascular resistance in surfactant-depleted
      newborn piglets. A more pronounced effect was observed after 200 mg/kg than after
      100mg/kg of Curosurf.

PMID- 9560039
TI  - Capillary refilling time in newborns--optimal pressing time, sites of testing and
      normal values.
AB  - Aspects of capillary refilling time (CRT) in newborns, such as pressing time,
      sites of testing, normal values and difference between observers were assessed.
      CRT was measured in 280 term newborns, divided into 7 groups of 40 each, varying
      pressing time (from 1 to 7 s) was applied. CRT was measured in midpoints of
      forehead and sternum and plantar surface of heel (defined as head, chest and
      heel). No statistically significant difference was found between 3 and 7 s
      pressing time groups. The data points of the CRT of the head and chest approached
      normality, whilst those of the heel were widely scattered. Normal CRT in newborns
      is <3 s. No significant difference between two observers in head and chest CRT
      values was found.

PMID- 9560040
TI  - The hypothalamic-pituitary-adrenal axis in preterm infants weighing < or = 1250
      g: association with perinatal data and chronic lung disease.
AB  - The hypothalamic-pituitary-adrenal axis (HPA) was examined in 34 ventilated
      preterm infants weighing < or = 1250 g during the first week of life to evaluate
      the association between adrenal suppression and subsequent chronic lung disease.
      The second aim of the study was to detect perinatal and clinical differences
      between the infants with and without persistent suppression of the HPA after
      completion of dexamethasone treatment for chronic lung disease. To evaluate the
      HPA, the corticotropin-releasing hormone stimulation test was performed, and the
      cortisol and adrenocorticotropic hormone (ACTH) levels were measured by
      radioimmunoassay. No association could be found between the synthesis of cortisol
      and ACTH at the end of the first week of life and the development of chronic lung
      disease. After treatment with dexamethasone, baseline cortisol levels < 138 nmol
      l(-1) were found in 12 infants (46.2%), 8 of whom (30.8%) had cortisol values
      below 83 nmol l(-1). The perinatal data of these patients did not differ from
      infants without HPA suppression. However, the infants with cortisol levels < 83
      nmol l(-1) after dexamethasone showed a significantly shorter need for mechanical
      ventilation and supplemental oxygen (p < 0.01) and a lower incidence of chronic
      lung disease (p < 0.05).

PMID- 9560041
TI  - Fatty acid balance studies in preterm infants fed formula milk containing long
      chain polyunsaturated fatty acids (LCP) II.
AB  - A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids
      (LCP) and with a fatty acid profile closely resembling breast milk has recently
      been introduced for preterm infants. A double-blind randomized controlled trial
      was performed comparing fatty acid absorption from Prematil-LCP (n=10) and
      standard Prematil (n=10). Formula-fed preterm infants underwent 3 d fat balances
      (once full enteral feeds were established) along with a parallel human milk fed
      group (n=11). Plasma samples were taken on the last day. Median total fat
      excretion (absorption, %) was 2.34g kg(-1) (82.0), 2.64g kg(-1) (82.9) and 1.65g
      kg(-1) (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively.
      This reflected differences in the excretion and absorption of long-chain
      saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was
      higher in infants fed human milk than in those fed Prematil-LCP, particularly for
      n-6 LCP (p < 0.01). Nevertheless, excreted LCP equated to < 30% dietary intake,
      with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected
      differences in dietary LCP intake.

PMID- 9560042
TI  - Infant Flow Driver or single prong nasal continuous positive airway pressure:
      short-term physiological effects.
AB  - The effectiveness of single prong nasal continuous positive airway pressure
      (CPAP) was compared with the Infant Flow Driver (IFD) in a crossover study in 20
      neonates treated with > or = 30% oxygen by nasal CPAP. They were randomized to
      the device used at the start of the study. Each infant was studied for four
      consecutive 2-h periods alternating between single prong nasal CPAP and the IFD.
      The FiO2 from the IFD read 0.02 higher than the same setting on the ventilators
      used for single prong nasal CPAP. The IFD improved the mean (95% CI) of the FiO2
      by 0.05 (0.02-0.08), p = 0.008. Taking into account the systematic error in the
      FiO2 between the devices the real mean improvement in FiO2 produced by the IFD
      was 0.03 (-0.005 to 0.06), p=0.09. There were no significant differences in
      respiratory rate, heart rate, blood pressure or comfort score of infants during
      periods of single nasal prong CPAP compared with periods on the IFD.

PMID- 9560043
TI  - Quality of general movements in preterm infants with transient periventricular
      echodensities.
AB  - By means of sequential videotape recordings, the relevance of the quality of
      general movements for neurological outcome was determined in a group of 21
      appropriate-for-gestational-age preterm infants with transient periventricular
      echodensities of variable localization and duration and in 6 infants without
      echodensities. Echodensities, especially in the parieto-occipital area, affected
      the quality of general movements. Echodensities persisting beyond 14d were
      associated with abnormal general movements; infants with echodensities up to 14 d
      had either normal or abnormal general movements. The developmental course of
      movement quality was correlated to neurological outcome (p < 0.005): normal
      outcomes were found in 11/12 infants with normal general movements throughout and
      in 9/11 infants with transient abnormal general movements; all 4 infants with
      persistent abnormal general movements had impaired outcomes. In infants with
      transient echodensities, longitudinal assessment of the quality of general
      movements helps to determine if there is brain dysfunction, either transient or
      persistent, and identifies infants at risk for impaired neurological outcomes.

PMID- 9560044
TI  - Immunogenicity of hepatitis B vaccine in term and preterm infants.
AB  - Some studies have suggested that decreased seroconversion rates might be found in
      premature infants with low birthweight (< 2000g) following administration of
      hepatitis B vaccine at birth. The aim of the present investigation was to
      evaluate possible differences in seropositive rates between full-term and preterm
      infants after primary vaccination, in particular when gestational age or
      birthweight is very low. Two-thousand and nine neonates born to HBsAg-negative
      mothers were vaccinated with 10 microg of recombinant hepatitis B virus (HBV)
      vaccine, from May 1991 to October 1994. Children with infections, congenital
      malformations or serious illnesses were excluded. HBV vaccine was administered
      intramuscularly, on the fourth day of life and again at 1 and 6 months of age. A
      1-ml blood sample was drawn from each infant 1 month after the third vaccine dose
      for determination of the level of anti-HBs antibody. The response to HBV
      vaccination was evaluated in 241 preterm (gestational age <38 weeks) infants and
      1727 term neonates. No statistical difference was observed in the distribution of
      anti-HBs antibody level, either between preterm infants (<38 weeks) and newborns
      of normal gestational age, or between low birthweight (<2500 g) and normal weight
      infants. The results suggest that preterm and low birthweight infants (<2500g)
      respond to HBV vaccine in the same measure as normal-term infants.

PMID- 9560045
TI  - Usefulness of short-term urine collection in the nutritional monitoring of low
      birthweight infants.
AB  - To establish adequacy of urine collection times shorter than 24h in the metabolic
      monitoring of low birthweight infants, we collected urine for 24 h in 39 LBW
      infants during the third and fourth week of life. All urine voidings over the 24
      h period were separately collected, the volume of each sampling and the time of
      voiding were recorded, and 20% of the volume was removed for pooling. All
      individual and pooled samples were analysed for total nitrogen, urea and ammonia,
      alpha-amino nitrogen, creatinine, sodium, potassium, calcium and phosphorus, and
      for each compound the ratio to 1 mol creatinine was established. Individual
      sample results were "pooled" to obtain 3-, 6- and 12-h period excretion and than
      related to the 24-h excretion as measured in the pooled 24-h sample. As the
      volume of urine obtained in any 6-h collecting period depended on the time of
      sampling (06:00-12:00 h, 17.5+/-3.1% of total; 12:00-18:00 h, 31.6+/-5.1% of
      total; 18:00-24:00 h, 25.6+/-3.1% of total; and 0:00-06:00h, 25.3+/-2.9% of
      total), calculations were based on samples obtained from 18:00 to 06:00 h. The
      correlation between results of 3- and 24 h-collection periods was weakest, while
      results of the 6-h collection correlated highly with the total daily excretion (r
      = between 0.82 and 0.93 for the different compounds) and the correlation was only
      slightly better when the 12-h collection period was considered. The correlation
      between the mean molar substrate/creatinine ratio of all individual samples of a
      24-h collecting period and the and total daily excretion of the respective
      substrate was weaker (r = between 0.46 and 0.76 for the different compounds) than
      the correlation between the results of a 6-h collecting period and the daily
      excretion is not as stable than in later life. The data indicate that 6-h urine
      sampling may be sufficient for metabolic monitoring of LBW infants. By contrast,
      urinary substrate/creatinine ratios are not good markers of the daily excretions
      of the respective substrate during the first weeks of life.

PMID- 9560046
TI  - Early detection of necrotizing enterocolitis by gastrointestinal tonometry.
AB  - The diagnosis of necrotizing enterocolitis (NEC) in neonates has traditionally
      depended on a combination of clinical signs, biochemical parameters and
      radiological changes. The measurement of intramucosal pH by gastrointestinal
      tonometry provides a simple means of long-term monitoring which may detect the
      development of NEC before conventional techniques. We present our experience of
      tonometry in two 'at risk' term neonates with Hypoplastic Left Heart Syndrome.

PMID- 9560047
TI  - Tension pneumopericardium in a preterm infant without mechanical ventilation: a
      rare cause of cardiac arrest.
AB  - A preterm infant with a gestational age of 32 weeks developed a tension
      pneumopericardium during the second day of life. The infant was treated with
      nasal continuous positive airway pressure and was not mechanically ventilated
      before pneumopericardium occurred. After emergency pericardiocentesis, two
      recurrences of pneumopericardium without clinical deterioration were diagnosed by
      X-ray during a 2-d observation period. A continuous pericardial drainage was
      positioned and was successfully removed on the seventh day of life after weaning
      from the ventilator. Tension pneumopericardium may occur even in non-ventilated
      newborns and should be considered as a rare but important differential diagnosis
      of cardiac arrest.

PMID- 9560048
TI  - Coexistence of acquired protein S and protein C deficiency and the Arg506Gln
      mutation in factor Va in a child with severe thromboembolic disease.
AB  - An 11-y-old girl who presented with cellulitis and clinical signs of deep vein
      thrombosis (DVT) is reported here. She developed staphylococcal sepsis, recurrent
      septic emboli and a large vegetation on the tricuspid valve. The patient was
      found to be heterozygous for the Arg506Gln mutation in factor Va and had low
      levels of protein C and protein S during the sepsis. The coexistence of the two
      thrombophilic states may explain the severe thromboembolic manifestations.

PMID- 9560049
TI  - Cutaneous polyarteritis nodosa in a child and a review of the literature.
AB  - The cutaneous form of polyarteritis nodosa in children is extremely rare.
      Findings are usually limited to the skin, muscles and joints. It has a benign but
      often chronic course. We describe an 8-y-old girl with cutaneous PAN, with
      extensive livedo reticularis on lower and upper extremities, tender subcutaneous
      nodules, arthralgia and right ankle swelling. Skin biopsy revealed vasculitis of
      small and medium-sized blood vessels characterized by fibrinoid necrosis. The use
      of prednisolone resulted in clinical improvement initially, but recurrence
      occurred during tapering. She showed marked improvement with additional high dose
      methyl prednisolone monthly.

PMID- 9560050
TI  - Breastfeeding and catch-up growth in SGA infants.

PMID- 9560051
TI  - Breastfeeding and catch-up growth in SGA infants: further comments.

PMID- 9560052
TI  - Current trends in chemotherapy for metastatic nonseminomatous testicular germ
      cell tumors.
AB  - With the introduction of cisplatin-based chemotherapy, metastatic testicular
      cancer represents a model for a highly curable malignant disease. Approximately
      70-80% of patients achieve a durable remission following chemotherapy +/-
      secondary surgery of residual tumors. With the development of prognostic
      classifications based on clinically available parameters, the aims of
      chemotherapy have been twofold: on the one hand, the reduction of toxicity in
      patients with 'low-risk' metastatic disease without a concomitant reduction in
      treatment efficacy and, on the other hand, the improvement of treatment results
      in patients with 'poor-prognosis' criteria who achieve a long-term cure rate of
      less than 50% with standard chemotherapy regimens. Despite a number of large
      randomized studies attempting either to avoid the toxicity of bleomycin or to
      reduce cisplatin-associated side-effects through the substitution with
      carboplatin, the combination of cisplatin, etoposide and bleomycin (PEB) given at
      3-week intervals still remains the standard treatment for metastatic disease. The
      role of high-dose chemotherapy with autologous stem cell support is currently
      being investigated in order to improve the outcome of patients with relapse after
      previous chemotherapy and of patients initially exhibiting advanced metastatic
      disease. For patients with relapsed disease receiving high-dose chemotherapy, a
      prognostic score has recently been developed: cisplatin-refractory disease, beta
      human gonadotropin values > 1,000 U/l or primary mediastinal germ cell tumors are
      factors characterizing patients which will profit less from high-dose
      chemotherapy treatment than patients with chemosensitive disease at relapse.
      Standard dose salvage regimens only result in a 20% long-term survival rate. In
      contrast, high-dose salvage chemotherapy may yield a cure rate of approximately
      40%. However, the only randomized study comparing high-dose versus conventional
      dose therapy in patients with relapsed disease is still ongoing. The
      investigation of dose-intensive approaches as first-line treatment is currently
      being studied by several institutions. Despite preliminary favorable results,
      this approach still cannot be considered standard treatment. A randomized study
      comparing high-dose chemotherapy with 4 cycles of standard PEB was initiated in
      the USA in 1996. The evaluation of new drugs in testicular cancer patients with
      absolute cisplatin-refractory disease has demonstrated that paclitaxel is one of
      the few agents with antitumor activity in these patients. Paclitaxel has
      therefore been included in combination regimens--such as cisplatin, ifosfamide
      and paclitaxel--for the treatment of patients with first and second relapse of
      testicular cancer. These combinations are used as induction therapy prior to high
      dose salvage treatment. Due to the large group of patients with metastatic
      disease being cured nowadays, the long-term side effects of treatment have become
      even more important. One of the major risk factors for the development of late
      toxicities such as oto-, neuro-, nephro-, gonadal and cardiovascular toxicity is
      the cumulative dose of cisplatin applied during therapy. The development of new
      treatment strategies, such as the use of adjuvant chemotherapy for stage I
      disease, the widespread application of high-dose chemotherapy with peripheral
      stem cell rescue and the use of new cytotoxic agents, makes the evaluation of the
      late effects of treatment for testicular cancer within controlled clinical trials
      mandatory.

PMID- 9560053
TI  - Prognosis and management strategies of lymphatic neoplasias in the elderly. I.
      Aggressive non-Hodgkin's lymphomas.
AB  - Lymphomas belong to the class of malignant diseases with the fastest increasing
      incidence. High-grade non-Hodgkin's lymphomas (NHL) display a peak of incidence
      in the age group above 65. In the last few years, age has been recognized as a
      major risk factor for overall survival of high-grade NHL patients, and numerous
      attempts have been made to analyze the contribution of factors to the age-related
      worsening of prognosis in this disease, e.g. the biology of the disease on the
      one hand, and age-specific comorbidity or degree of cytotoxicity, reluctance in
      diagnosis and treatment and socioeconomic factors on the other. Furthermore, age
      adapted treatment protocols have been designed and tested for their
      practicability and efficacy in the elderly. Very recently, large randomized
      prospective clinical trials have been carried out which support the idea that
      treatment with a curative intent is warranted even in the very elderly and that a
      successful attempt to cure requires the use of full-dose anthracycline-containing
      regimens closely similar to CHOP (cyclophosphamide, doxorubicin, vincristine,
      prednisone). In addition, progress has been made in systematically defining
      maximally tolerated doses of the cytotoxic drugs and in specifically testing
      anthracyclines with reduced cardiotoxicity with an efficacy similar to that of
      doxorubicin, and further in investigating the advantage of applying hematopoietic
      growth factors and/or cardioprotective drugs in this older population. In limited
      stages of disease, three cycles of CHOP chemotherapy followed by involved field
      irradiation may be superior to radiotherapy and prolonged chemotherapy and may
      produce highly satisfying cure rates.

PMID- 9560054
TI  - Management of stage III breast cancer.
AB  - Stage III breast cancer encompasses a heterogeneous group of patients. According
      to the American Joint Committee on Cancer (AJCC) these tumors include stage IIIA
      and stage IIIB disease, the first generally being operable but the second
      inoperable. Patients with inflammatory breast cancer are also included in stage
      IIIB disease, and these patients have the worst prognosis. Multidisciplinary
      therapy has become the treatment of choice for these patients. Primary or
      neoadjuvant chemotherapy, followed by locoregional therapy, either surgery,
      radiotherapy or both, is now an accepted strategy. Most patients achieve a
      response to chemotherapy, resulting in downstaging of the tumor, and 5-year
      survival rates have improved from 10-20% with local therapy alone to 30-60% with
      the multidisciplinary approach. Although many prospective, mainly phase II trials
      have been performed in stage III breast cancer, the optimal treatment scheme
      still has to be established. The role of new therapeutic strategies such as high
      dose chemotherapy with hematopoietic stem cell rescue and higher dose intensity
      regimens with hematopoietic growth factors is currently under investigation. This
      article will review the literature and discuss our own research in this area.

PMID- 9560055
TI  - Paclitaxel in cisplatin or carboplatin-pretreated ovarian cancer. Phase II study.
AB  - A phase II trial was conducted in order to assess the efficacy and toxicity of
      paclitaxel given at a dose of 175 mg/m2 in a 3-hour infusion every 3 weeks in
      patients with recurrent or cisplatin (CDDP) carboplatin-refractory ovarian
      cancer. Forty-two patients with a median age of 61 years (range 34-76 years)
      entered the study. Most patients had bulky disease. Thirty-three patients (78.5
      %) presented with stage III and IV diseases. Twenty-two patients (52.3%) had
      previously been treated with only 1 regimen and 20 patients (47.7%) with > or = 2
      regimens. The median treatment interval from the last previous therapy was 4.5
      months (range 2-26 months). From 41 patients evaluable for response, 3 (7.3%)
      achieved a complete and 4 (9.8%) a partial response. All 3 complete and 2 out of
      the 4 partial responders had previously received > or = 2 chemotherapeutic
      regimens. Grade 3-4 toxicities included granulocytopenia (35%), which was of
      short duration, neurotoxicity (9.75%) and alopecia (60.9%). Two patients with
      grade 4 neutropenia were hospitalized due to pneumonia, which was successfully
      treated by broad-spectrum antibiotics and administration of G-CSF. A severe
      hypersensitivity reaction occurred in 1 patient early during the first cycle,
      resulting in discontinuation of treatment. Median relapse-free survival was 6.9
      months, median time to progression 6.2 months and median survival 13.2 months. In
      conclusion, paclitaxel given at a dose of 175 mg/m2 as a 3-hour infusion every 3
      weeks appears to be an efficacious and well-tolerated treatment in patients with
      recurrent or CDDP/carboplatin-refractory ovarian cancer.

PMID- 9560056
TI  - Mucosal squamous cell carcinoma of the esophagus: a clinicopathologic study of 30
      cases.
AB  - A clinicopathologic study was carried out on 30 patients with mucosal esophageal
      cancer (MEC). The depth of cancer invasion was subdivided histologically into
      three categories: m1 = carcinoma in situ (intraepithelial carcinoma) or carcinoma
      with questionable invasion beyond the basal membrane; m2 = cancer invasion
      confined to the lamina propria, and m3 = cancer reaching to or infiltrating into
      the muscularis mucosae. Lymph node metastases and lymphatic invasion were found
      only in the tumors reaching or infiltrating the muscularis mucosae (m3). The
      maximum histologic vertical extent of the tumors was more than 1 mm in 4 of 5
      patients with lymph node metastasis or lymphatic invasion. None of the patients
      died of recurrent esophageal disease, and 3 of the 6 patients who had a second
      primary tumor died of this other malignancy. It is critical to distinguish
      between m1, m2 and m3 tumors to plan a treatment strategy, including an
      endoscopic mucosal resection.

PMID- 9560057
TI  - Expression of insulin-like growth factor-2 can predict the prognosis of human
      colorectal cancer patients: correlation with tumor progression, proliferative
      activity and survival.
AB  - Expression of insulin-like growth factor-2 (IGF-2) has been reported in tissue
      specimens and cell lines of human colorectal cancers. However, the effects of IGF
      2 in colorectal cancer patients are not well known. In this study, IGF-2 staining
      was performed on tissue samples from 92 patients with colorectal cancer, and the
      relationship of IGF-2 staining to clinicopathological variables, proliferating
      cell nuclear antigen (PCNA) staining and patient survival was analyzed. IGF-2
      staining was correlated with tumor progression, PCNA staining and patient
      survival. Our results suggest that IGF-2 plays an important role in tumor
      progression and that IGF-2 staining is useful as a prognostic factor in
      colorectal cancer patients.

PMID- 9560059
TI  - Correlation between telomerase activity and DNA ploidy in gastric cancer.
AB  - Telomerase has been reported to be activated in most immortal cells and human
      cancers. In the present study, we assessed the correlation between telomerase
      activity and cellular DNA ploidy level in gastric cancer. Telomerase activity was
      determined semiquantitatively using the telomeric repeat amplification protocol
      assay, a polymerase-chain-reaction-based assay, in surgical specimens of primary
      tumors obtained from 36 patients with gastric cancer. No correlation was observed
      between telomerase activity and the proliferating cell nuclear antigen labeling
      index. In contrast, a positive linear correlation was observed between telomerase
      activity and the DNA index (r = 0.59; p < 0.01). Tumor cells with aneuploid
      patterns showed higher telomerase activity than those with diploid patterns
      (27.6+/-5.8 vs. 5.8+/-1.1%; p < 0.01). Telomerase activity of tumors with liver
      metastases was significantly higher than activity of those without metastases
      (34.5+/-16.6 vs. 11.8+/-2.4; p < 0.05). There was a trend toward a lower survival
      rate in 9 patients with a telomerase activity of 20% or higher compared to 27
      patients with telomerase activity lower than 20%. These results suggest that the
      telomerase activity of gastric cancer tissue may reflect the malignant potential
      of the tumor.

PMID- 9560058
TI  - Comparative survival analysis of p53 gene mutations and protein accumulation in
      colorectal cancer.
AB  - Immunohistochemical reactivity for p53 protein is common in various human
      malignancies. Increased intracellular concentration of p53, which is frequently,
      but not systematically, related to p53 mutation, has been proposed to be
      associated with poor prognosis in some tumor types. In colorectal cancer, this
      significance is still a matter of debate. To directly investigate the
      relationship between prognosis and p53 alterations, we screened a series of 72
      colorectal carcinomas for overexpression and mutation of the p53 gene. Mutations
      in exons 5-9 of the p53 gene were assayed by single-strand conformation
      polymorphism and direct DNA sequencing, whereas p53 protein accumulation was
      detected in 10-microm frozen tissue by immunostaining using 2 different
      monoclonal antibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53
      overexpression. Nineteen of the 36 tumors which contained high levels of p53
      protein were found to have missense point mutations. Using a multivariate
      survival analysis, stage, differentiation, p53 immunoreactivity and p53 mutation
      emerged as risk factors, but only the stage was significant. In univariate
      analysis, stage, differentiation and p53 immunoreactivity were significant
      prognostic indicators, while p53 mutation was at the borderline of significance.

PMID- 9560060
TI  - Undertreatment of hypertension in older Mexican Americans.
AB  - OBJECTIVE: To identify the prevalence of hypertension and factors associated with
      nontreatment and poor control of hypertension in Mexican Americans aged 65 years
      and older. DESIGN: A population-based survey of older Mexican Americans conducted
      in 1993-1994. SETTING: Subjects residing in five Southwestern states: Texas, New
      Mexico, Colorado, Arizona, and California. PARTICIPANTS: An area probability
      sample of 3050 noninstitutionalized Mexican American men and women aged 65 and
      older took part in a 90-minute in-home interview, which included review of all
      medications taken and two sitting blood pressure measurements. OUTCOME MEASURES:
      Measured were previous diagnoses of hypertension, current medication for
      hypertension, and current blood pressure RESULTS: Sixty-one percent of older
      Mexican-Americans were hypertensive, and 51% of those with hypertension were
      taking antihypertensive medications. Only 25% of hypertensive subjects (18% of
      males and 30% of females) were in good blood pressure control (i.e., systolic
      blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg). In
      multivariate analyses, factors associated with increased likelihood of treatment
      included female gender (OR = 1.9), history of heart disease (OR = 2.4),
      possessing a regular source of health care (OR = 2.7), and having seen a
      physician two or more times in the previous year (OR = 3.8). These were also
      independent predictors of good blood pressure control. CONCLUSION: Nontreatment
      of hypertension is still a major public health concern in older Mexican
      Americans. We estimate that adequate blood pressure control in this population
      would prevent approximately 30,000 adverse cardiovascular events over 10 years,
      affecting approximately 6% of the entire Mexican American older population.

PMID- 9560061
TI  - Lower-extremity functioning in older Mexican Americans and its association with
      medical problems.
AB  - OBJECTIVE: To describe lower-extremity functioning in community-dwelling older
      Mexican Americans and to examine its relationship with medical problems. DESIGN:
      Cross-sectional analyses of survey and performance-based data obtained in a
      population-based study employing area probability sampling. SETTING: Households
      within selected census tracts of five Southwestern states: Arizona, California,
      Colorado, New Mexico, and Texas. PARTICIPANTS: A total of 2873 Mexican Americans
      aged 65 years and older. MEASUREMENTS: A multidimensional questionnaire assessing
      demographic, sociocultural, and health variables. Standardized tests of lower
      extremity physical functioning included measures of standing balance, repeated
      chair stands, walking, and an overall summary measure. RESULTS: Regression
      analyses revealed that being more than age 75 and female, having arthritis
      diabetes, visual impairments, or being obese or underweight were all
      significantly associated with performance on both individual and summary tests of
      lower-extremity functioning. In separate regression analyses, the total number of
      medical conditions was also associated with performance. CONCLUSIONS: The
      likelihood of predicting performance or inability to complete tests of lower
      extremity functioning was greatest for those aged 80 and older, those with
      arthritis or diabetes, and those with three or more medical conditions. Because
      of the high prevalence of diabetes in Mexican Americans, documentation of the
      association of diabetes with performance-based tests of lower-extremity
      functioning may help guide early interventions targeted to prevent progression to
      more severe limitations or disability.

PMID- 9560062
TI  - Predicting hospitalization and functional decline in older health plan enrollees:
      are administrative data as accurate as self-report?
AB  - OBJECTIVE: To compare the predictive accuracy of two validated indices, one that
      uses self-reported variables and a second that uses variables derived from
      administrative data sources, to predict future hospitalization. To compare the
      predictive accuracy of these same two indices for predicting future functional
      decline. DESIGN: A longitudinal cohort study with 4 years of follow-up. SETTING:
      A large staff model HMO in western Washington State. PARTICIPANTS: HMO Enrollees
      65 years and older (n = 2174) selected at random to participate in a health
      promotion trial and who completed a baseline questionnaire. MEASUREMENT:
      Predicted probabilities from the two indices were determined for study
      participants for each of two outcomes: hospitalization two or more times in 4
      years and functional decline in 4 years, measured by Restricted Activity Days.
      The two indices included similar demographic characteristics, diagnoses, and
      utilization predictors. The probabilities from each index were entered into a
      Receiver Operating Characteristic (ROC) curve program to obtain the Area Under
      the Curve (AUC) for comparison of predictive accuracy. RESULTS: For
      hospitalization, the AUC of the self-report and administrative indices were .696
      and .694, respectively (difference between curves, P = .828). For functional
      decline, the AUC of the two indices were .714 and .691, respectively (difference
      between curves, P = .144). CONCLUSIONS: Compared with a self-report index, the
      administrative index affords wider population coverage, freedom from nonresponse
      bias, lower cost, and similar predictive accuracy. A screening strategy utilizing
      administrative data sources may thus prove more valuable for identifying high
      risk older health plan enrollees for population-based interventions designed to
      improve their health status.

PMID- 9560063
TI  - Detecting balance deficits in frequent fallers using clinical and quantitative
      evaluation tools.
AB  - OBJECTIVE: This investigation sought to determine whether older idiopathic
      frequent fallers could be distinguished from healthy older adults on the basis of
      balance and movement coordination tests. A secondary objective was to determine
      the relationships among clinical balance test scores, balance performance data
      obtained by accelerometry, and quantitative motor coordination tests. DESIGN: Two
      group comparison designs. SETTING: A motor control research laboratory in a
      university setting. PARTICIPANTS: The 16 subjects recruited for this study
      included eight healthy older subjects and eight age-matched idiopathic fallers.
      MEASUREMENTS: Each participant's balance performance was assessed by
      accelerometry, as well as by coordination and clinical tests. Accelerometry
      scores, obtained by 1g accelerometers placed at the hip and on the head, were
      made with eyes open or closed, either standing on the floor or on a wedge of
      compliant foam. Clinical balance scores were obtained using variants of Romberg's
      test and the functional reach test. Motor coordination tests obtained included
      the heel-to-toe transition and rapid stepping tests. MAIN RESULTS: Statistically
      significant differences were obtained between groups for all accelerometry
      variables except root mean square. All accelerometry variables were successful in
      discriminating between head and hip sites. Moreover, the amplitude of sway
      obtained from accelerometry data identified significant differences among the
      four test conditions. The Romberg test, using right leg alone with eyes open,
      showed a significant difference between fallers and healthy older subjects.
      Walking velocity was significantly faster for normal older subjects than for
      fallers (1.10 m/sec vs 0.80 m/sec). No significant between-group differences were
      obtained using the functional reach test. Coordination skills yielded significant
      between-group differences using the rapid stepping test but no significant
      differences between groups with the heel-toe transition test. CONCLUSION:
      Accelerometry is an inexpensive and clinically useful technique that can
      distinguish between healthy older people and idiopathic frequent fallers. In
      conjunction with clinical procedures and commercially available tests to assess
      motor coordination, these techniques can identify older individuals susceptible
      to frequent falls.

PMID- 9560064
TI  - Thioridazine dose-related effects on biomechanical force platform measures of
      sway in young and old men.
AB  - OBJECTIVE: Thioridazine (TDZ) is associated with an increased risk of falls. The
      purpose of this study was to determine whether (1) thioridazine increases
      Biomechanics Force Platform (BFP) measures of sway in a dose-related manner, (2)
      there is a difference in sway between young and old men, (3) there is a
      correlation between sway and orthostatic changes in BP and HR. DESIGN: Seven
      younger (aged 20-42) and five older (aged 70-76) healthy male volunteers
      received, in a randomized order double-blind design, a single oral dose of 0, 25,
      and 50 mg of TDZ on three separate days at least 7 days apart and 75 mg on the
      fourth day of the study. Sway and blood pressure were measured for 24 hours.
      SETTING: A general clinical research center. MEASUREMENTS: Biomechanics force
      platform measures of postural sway were measured as the movement of the center of
      pressure. The elliptical area (EA) and average velocity (AV) were calculated with
      eyes open and eyes closed. Blood pressure and heart rate were measured for 5
      minutes supine and 5 minutes standing. RESULTS: Thioridazine increases BFP sway
      in a dose-dependent manner. EA increased from 0.56 (SD = .51) cm2 for placebo to
      0.88 (SD = 1.09) cm2 for 75 mg TDZ. AV increased from 1.07 (SD = .27) cm/sec,
      placebo, to 1.43 (SD = .55) cm/sec, 75 mg TDZ. Older men swayed more than younger
      men. Changes followed the expected time course for TDZ. EA and AV were associated
      with HR and BP, e.g., SBP versus ln(EA) and ln(AV) (r = -0.21 and r = -0.22,
      respectively; P < .0001). CONCLUSIONS: Thioridazine increases validated measures
      of fall risk dose dependently in young and old men. This may explain the effects
      of neuroleptic drugs on fall risk in older people.

PMID- 9560065
TI  - A prospective study of posturography in normal older people.
AB  - OBJECTIVE: To follow posturographic measurements over time in a group of normal
      older subjects to see if sway increases with aging and if sway is greater in
      those with deteriorating balance and falls. SUBJECTS: Seventy-two community
      dwelling older people (age range 79-91 years), who initially had normal
      neurological evaluations, were followed with three yearly follow-up examinations.
      MEASUREMENTS: Amplitude and velocity of sway on static and dynamic posturography,
      Tinetti gait and balance score, reports of falls. RESULTS: Velocity of sway on
      dynamic tests increased significantly during the 3 years of follow-up. The
      percentage increase in sway was about the same in the anterior-posterior and
      medial-lateral directions and with eyes open and eyes closed. Subjects with low
      Tinetti scores had higher sway amplitude and velocity, particularly on dynamic
      tests, but no measure of sway was significantly different in those who reported
      falls compared with those who did not report falls. CONCLUSIONS: Sway increases
      in normal subjects over time, and sway is greater in older subjects with
      deteriorating balance compared with those with normal balance. Sway was not
      greater in those who fell compared with those who did not fall, probably because
      falls are highly dependent on individual behavior.

PMID- 9560066
TI  - Prognostic factors in very old demented adults: a seven-year follow-up from a
      population-based survey in Stockholm.
AB  - OBJECTIVE: To detect prognostic factors in very old demented subjects with
      Alzheimer's disease (AD), vascular dementia (VaD), and other types of dementia
      (OD). DESIGN: Follow-up clinical examinations of dementia patients from a
      population-based study after 3- and 7-year intervals. SETTING AND PARTICIPANTS:
      In an established population aged 75 years and older in Stockholm, Sweden, there
      were 133 cases of AD, 52 of VaD, and 38 of OD. MAIN OUTCOME MEASURES: Predictors
      of survival at 3- and 7-year follow-up examinations were evaluated by Cox
      proportional hazard models. Progression was measured as the annual rate of change
      in Mini-Mental State Examination (MMSE) scores. Linear models were used to
      evaluate predictors of progression. RESULTS: Older age, male gender, low
      education, comorbidity, and functional disability predicted shorter 7-year
      survival in the 223 prevalent dementia cases. Other factors, including type of
      dementia, dementia severity, and duration of the disease were not significant.
      The average rate of cognitive decline in the 81 mild to moderate demented
      subjects who survived 3 years was 2.4 MMSE points per year. Type of dementia (AD
      vs OD), higher baseline cognitive function, and greater functional disability
      predicted faster decline. Despite similar survival probability, predictors of
      death varied as a function of dementia type: Older age (for AD and VaD),
      comorbidity (for AD and OD), and functional dependency (for VaD). In AD,
      prognostic factors were similar to those described for the combined dementia
      groups, with the exception of an accelerated cognitive decline among women.
      CONCLUSIONS: Although methodological difficulties exist, it is possible to
      identify demented subjects with worse prognoses (shorter survival and faster
      cognitive decline) by using clinical and demographic data. Clinicians and
      healthcare planners should be aware of the potential usefulness of functional
      dependence as a prognostic indicator. Finally, the need for careful clinical
      examinations of demented subjects is stressed by the increased mortality found
      among those demented who are also affected by other chronic conditions.

PMID- 9560067
TI  - Atrial natriuretic peptide level contributes to a model of future mortality in
      the oldest old.
AB  - OBJECTIVES: To determine if atrial natriuretic peptide (ANP) level is associated
      with mortality in the oldest old and to develop a comprehensive model of
      mortality in the oldest old using clinical and laboratory parameters. DESIGN:
      Prospective cohort study with 7 years of follow-up. SETTING: A 725-bed life care
      facility. PARTICIPANTS: 282 frail older individuals (mean age 88, range 70-102).
      MEASUREMENTS: Variables measured included age, gender, Charlson Comorbidity
      Index, functional measurements, weight, blood pressure, and multiple laboratory
      variables, including ANP. Main outcome measurement was death. RESULTS: Eighty
      four percent (237/282) of subjects died during the 7-year follow-up period. On
      univariate analysis, the risk ratio (RR) for ANP tertile was 1.28. On bivariate
      analysis, adjusting for the development of congestive heart failure, the RR was
      1.22. On multivariate analysis, the following variables were associated with
      mortality: ANP tertile (RR 1.24), age (RR 1.04), female gender (RR 0.43),
      Charlson Comorbidity Index score (RR 1.13), mentation score (RR 1.27), BUN/Cr
      ratio (RR 1.04), albumin level (RR 0.63), and hemoglobin level (RR 0.84).
      CONCLUSIONS: ANP level and other variables are independent risk factors for
      mortality in frail individuals. ANP level may indicate homeostatic failure to
      adapt to fluid volume changes or may reflect subclinical heart disease. ANP level
      contributes to a multivariate model of mortality in frail older individuals.

PMID- 9560068
TI  - Relationships between sleep and body temperature in middle-aged and older
      subjects.
AB  - OBJECTIVES: Although changes in the circadian timing system are thought to be a
      major factor in the decline of sleep quality that often accompanies aging, few
      reports have actually examined this relationship in detail. Because some
      treatments for age-related insomnia are based on putative circadian changes, it
      is important to expand the limited database that specifically addresses this
      issue. This study examined age-related changes in sleep, and relationships
      between those sleep changes and alterations in the circadian timing system, in a
      group of middle-aged and older subjects. DESIGN: Sixty healthy men and women
      between the ages of 40 and 84 were studied. A subset of older subjects (< 65
      years) had reported sleep disturbance for at least 1 year before participation.
      Polysomnography was obtained, and body core temperature was recorded continuously
      for 24 hours. All recordings took place in the Laboratory of Human Chronobiology,
      Department of Psychiatry, Cornell University Medical College. RESULTS: There were
      no differences in sleep quality between middle-aged and non-sleep-disturbed older
      subjects. However, timing of the minimum body temperature was earlier in the
      older non-sleep-disturbed subjects than in the middle-aged group. In contrast,
      sleep-disturbed older people had shorter total sleep times, reduced sleep
      efficiency, more waking time after sleep onset, and a reduced proportion of REM
      sleep compared with non-sleep-disturbed older subjects. Yet, there were no
      differences between the two older groups in the rhythm of body temperature. For
      the entire group, age was correlated negatively with total sleep time, sleep
      efficiency, percentage of stage 2 sleep, and the timing of the temperature
      minimum. CONCLUSION: The results support the widely held notion that sleep and
      circadian rhythm changes occur with aging. However, the hypothesis that age
      related changes in sleep may be associated with aging of the circadian system was
      supported only to a limited degree, suggesting that age-related sleep disturbance
      is likely to have multiple causes. Thus, treatment strategies that incorporate a
      combination of interventions may be the most effective.

PMID- 9560069
TI  - Nighttime urinary incontinence and sleep disruption among nursing home residents.
AB  - OBJECTIVE: To examine the relationship of urinary incontinence episodes to sleep
      disruption in a sample of nursing home residents. DESIGN: Descriptive, case
      series. SETTING: Three community nursing homes. PARTICIPANTS: Seventy-three
      incontinent residents of three nursing homes participating in a trial of a
      behavioral intervention for nighttime urinary incontinence. MEASUREMENTS: Data
      were collected during a baseline and repeat baseline period about 2 months later
      in nursing homes serving as controls for the intervention homes. Incontinence
      episodes were identified by incontinence pads, which were wired to detect wetness
      of 10 mL or more. Sleep was monitored by wireless wrist actigraphs. Noise and
      light changes were monitored by bedside recording devices. MAIN RESULTS:
      Recordings covered 403 nights, during which 1715 awakenings from 10 consecutive
      minutes of sleep were detected as were 1168 incontinent episodes. Only 4% of the
      awakenings were associated with an incontinence episode, and only 23% of the
      incontinence episodes occurred during periods of at least 10 consecutive minutes
      of sleep. Of the latter episodes, only 12% appeared to awaken the resident.
      CONCLUSIONS: Our data raise questions about the relevance of incontinence
      episodes to sleep disruption among chronically incontinent nursing home
      residents. Our findings must be interpreted cautiously because of limitations in
      the technologies and definitions we used to identify sleep, awakenings, and
      incontinence episodes. Although logistically and technically difficult to
      perform, studies using polysomnographic recordings of sleep are needed to examine
      further these important associations.

PMID- 9560070
TI  - Urinary incontinence in a community-based cohort: prevalence and healthcare
      seeking.
AB  - OBJECTIVE: To estimate the prevalence of urinary incontinence and to assess care
      seeking behavior for urinary symptoms among community-dwelling people. DESIGN: A
      community-based cross-sectional study. SETTING: Randomly selected men and women
      from Olmsted County, Minnesota. PARTICIPANTS: Two cohorts, one comprised of both
      men (n = 778) and women (n = 762) 50 years of age or older and a second comprised
      of men aged 40 years or older (n = 2150). MEASUREMENTS: Participants completed
      questionnaires assessing urinary incontinence in the previous 12 months, the
      number of days leaked, the amount leaked, and healthcare-seeking measures for
      urinary symptoms. RESULTS: In the first cohort, the prevalence of incontinence
      was 24% in men and 49% in women; 29% of men and 13% of women with incontinence
      had sought care for urinary symptoms. Urinary incontinence was more strongly
      associated with care-seeking measures for urinary symptoms in men (Odds Ratio
      (OR) = 4.3, 95% Confidence Interval (CI) = 2.4, 8.0) than in women (OR = 2.1, 95%
      CI = 1.2, 3.9). Moderate or severe urinary incontinence was associated
      significantly with care-seeking for urinary symptoms (OR = 10.5, 95% CI = 5.6,
      19.8). In the second cohort, the prevalence of urinary incontinence was 17.3%;
      8.5% of men with incontinence had sought care for urinary symptoms. Men with
      incontinence were 1.2 times (95% CI = .8, 1.9) as likely to seek care for urinary
      symptoms as men without incontinence. CONCLUSION: Our findings indicate that
      although urinary incontinence is relatively common in the community, care-seeking
      for urinary symptoms among persons with urinary incontinence is low, particularly
      among women, for whom the prevalence exceeds 40% between the ages of 50 and 70
      years. These findings suggest that strategies to promote care-seeking for
      incontinence need to be investigated and employed in the community.

PMID- 9560071
TI  - Variation in estimates of urinary incontinence prevalence in the community:
      effects of differences in definition, population characteristics, and study type.
AB  - OBJECTIVES: Prevalence estimates for urinary incontinence among community
      dwelling adults vary from 2 to 55%. A review of the literature was undertaken to
      investigate the degree to which differences in definitions of incontinence, age,
      and gender of the populations studied, response rates, measurement techniques, or
      location could explain differences in reported prevalences. DESIGN: A literature
      search was conducted to locate all studies published in English reporting the
      prevalence of urinary incontinence in a population-based sample of adults.
      MEASUREMENT: Information was abstracted for study size, response rate, type of
      survey, definition of urinary incontinence, and prevalence of incontinence by age
      group and gender. Prevalence by type of incontinence was also abstracted where
      available. Stratification was used to obtain prevalence estimates specific for
      age, gender, and frequency of incontinence. Data were examined for associations
      between prevalence and survey type, response rate, year, and location of survey.
      RESULTS: A total of 21 studies met inclusion criteria. Stratification of reported
      prevalence by frequency, gender, and age substantially reduced the variation in
      prevalence estimates. For older women, the estimated prevalence of urinary
      incontinence ranged from 17 to 55% (median = 35%, pooled mean = 34%), and for
      daily incontinence it ranged from 3 to 17% (median = 14%, pooled mean = 12%). For
      older men, incontinence prevalence was estimated to be 11 to 34% (median = 17%,
      pooled mean = 22%), and 2 to 11% reported daily incontinence (median = 4%, pooled
      mean = 5%). Within studies, the prevalence of any incontinence was 1.3 to 2.0
      times greater for older women than for older men. Among middle-aged and younger
      adults, prevalence of incontinence ranged from 12 to 42% (median = 28%, pooled
      mean = 25%) for women and from 3 to 5% (median = 4%, pooled mean = 5%) for men.
      The ratio of prevalence of any incontinence for women to men in this age group
      ranged from 4.1 to 4.5. Stress incontinence predominated in younger women,
      whereas urge and mixed incontinence predominated in older women. There was a
      tendency for studies using in-person interviews to report higher prevalences.
      CONCLUSIONS: An accurate estimate of the prevalence of urinary incontinence
      depends on specifying the definition of incontinence and the age and gender
      groups of interest.

PMID- 9560072
TI  - Prevalence of coronary artery disease, atherothrombotic brain infarction, and
      peripheral arterial disease: associated risk factors in older Hispanics in an
      academic hospital-based geriatrics practice.
AB  - OBJECTIVE: To investigate the prevalence of coronary artery disease (CAD),
      atherothrombotic brain infarction (ABI), and peripheral arterial disease (PAD) in
      older Hispanics and the association with risk factors in this population. DESIGN:
      A retrospective analysis of charts from all Hispanics seen during January 1996
      through July 1997 at an academic hospital-based geriatrics practice. SETTING: An
      academic, hospital-based, primary care geriatrics practice staffed by fellows in
      a geriatrics training program and by full-time faculty geriatricians. PATIENTS:
      One hundred sixty women and 53 men, mean age 80 +/- 8 years (range 64 to 100),
      were included in the study. MEASUREMENTS AND MAIN RESULTS: Of 213 Hispanics in
      the study, 59 (28%) had documented CAD, 43 (20%) had ABI, 34 (16%) had PAD, and
      90 (42%) had either CAD, ABI, or PAD. Serum total cholesterol and triglycerides
      were measured in 202 of 213 subjects (95%). Serum high-density lipoprotein
      cholesterol was measured in 137 of 213 patients (64%). Other risk factor data
      were documented in all patients. Multiple logistic regression analysis performed
      in 202 patients using the variables age, gender, cigarette smoking, hypertension,
      diabetes mellitus, obesity, serum total cholesterol, and serum triglycerides
      showed statistically significant associations between prevalent CAD, ABI, or PAD
      and age (P = .002, odds ratio (OR) = 1.083), cigarette smoking (P = .002, (OR) =
      3.865), hypertension (P = .007, (OR) = 2.749), diabetes mellitus (P = .028, (OR)
      = 2.386), obesity (P = .014, (OR) = 2.608), serum total cholesterol (P < 0.001,
      (OR) = 1.025), and serum triglycerides (P = .017, (OR) = .993). CONCLUSIONS:
      Either CAD, ABI, or PAD was present in 42% of 213 older Hispanics. There were
      statistically significant associations between prevalent CAD, ABI, or PAD in
      older Hispanics and risk factors, including age, cigarette smoking, hypertension,
      diabetes mellitus, obesity, and serum total cholesterol.

PMID- 9560073
TI  - Age dependence of choroidal blood flow.
AB  - OBJECTIVE: To investigate the age dependence of choroidal blood flow. DESIGN: A
      cross-sectional study. SETTING: Department of Clinical Pharmacology, Vienna
      University. PARTICIPANTS: A total of 130 healthy volunteers between the ages of
      19 and 83 years. MEASUREMENTS: Fundus pulsation amplitude (FPA) with a recently
      developed laser interferometric method, mean arterial pressure (MAP) with an
      automated oscillometric device, intraocular pressure (IOP) with an applanation
      tonometer, and ocular perfusion pressure (OPP) as calculated from MAP and IOP.
      RESULTS: There was a significant correlation of FPA with age r = -0.242 (P =
      .005). MAP, IOP, and OPP showed a significant positive correlation with age.
      Multiple regression analysis showed that FPA is associated with age but not with
      MAP, IOP, or OPP. CONCLUSION: Choroidal blood flow is reduced in older subjects,
      which argues in favor of an increase in ocular vascular resistance with age. This
      may be a risk factor in the development of common ocular diseases such as age
      related macular degeneration or glaucoma.

PMID- 9560074
TI  - A census-based comparison of centenarians in New Zealand with those in the United
      States.
AB  - OBJECTIVE: To describe the characteristics of New Zealand's centenarians, as
      given in the 1991 census, and to compare these characteristics with those of
      centenarians from the United States. DESIGN: A census-based descriptive study.
      SETTING: The complete national population as defined by the 1991 New Zealand
      census. RESULTS: In 1991, there were 246 female and 51 male centenarians in New
      Zealand. Fifty-one percent of the men and 29% of the women lived at home; 16%
      lived at home with someone else (55% with children). People who were widowed were
      more likely to be living in a residential institution (69%) than people who were
      married (40%). Forty-three percent of men and 39% of women earned less than
      NZ$10,000 per year. Most had no formal educational qualification. Fourteen
      percent of men and 35% of women living at home did housework in the previous
      week. Compared with the United States, there are fewer New Zealand centenarians
      per number of population. People of European race were overrepresented in the New
      Zealand centenarian population, whereas African Americans were overrepresented in
      the United States centenarian population. CONCLUSIONS: Our data have shown the
      heterogeneity associated with extreme ageing and can be used as a basis for
      comparison with other countries.

PMID- 9560075
TI  - Cross-cultural adaptation of the hearing handicap inventory for the Elderly
      Screening Version (HHIE-S) for use with Spanish-speaking Mexican Americans.
AB  - OBJECTIVE: To cross-culturally adapt the Hearing Handicap Inventory for the
      Elderly-Screening Version (HHIE-S) for use with older Spanish-speaking Mexican
      Americans. SUBJECTS AND SETTING: Two different samples were used. First, a
      convenience sample of 100 older community-dwelling Mexican American men and women
      in San Antonio, Texas, was used to test technical equivalence of the Spanish and
      English language versions of the HHIE-S. Second, a neighborhood-based sample of
      older Mexican Americans was used to establish conceptual (n = 433) and criterion
      equivalence (n = 381) of the two HHIE-S language versions. METHODS: Independent
      forward and back translations were done to create a Spanish language version of
      the HHIE-S. In the convenience sample, subjects were administered the English and
      Spanish HHIE-S in random order on separate days. In the neighborhood sample, the
      HHIE-S was given on one occasion in the language of the subject's preference.
      Depressive symptoms were assessed using the Geriatric Depression scale to see if
      the two language versions of the HHIE-S were similarly associated with depression
      (conceptual equivalence). Hearing impairment was assessed using the Welch-Allyn
      Audioscope to see if the two language versions were similarly associated with an
      audiometric measure for hearing loss (criterion equivalence). RESULTS: In the
      convenience sample, the overall mean (SD) Spanish and English HHIE-S scores were
      6.2 (8.7) and 6.2 (9.3), respectively (P = 1.00). Total scores of the English and
      Spanish versions were highly correlated (r = .89), and regression analysis
      indicated that the two language versions gave nearly identical results. In the
      neighborhood-based sample, men had higher HHIE-S scores than women (OR 2.0, 95%
      CI = 1.3-3.5). Having depressive symptoms (OR 3.2, 95% CI = 1.9-5.5) or hearing
      impairment (OR 6.1, 95% CI = 3.5-10.5) was associated with higher HHIE-S scores.
      After adjustment for gender, depressive symptoms, and/or hearing impairment, the
      language of interview was not associated with HHIE-S score. CONCLUSION: We have
      developed and tested a Spanish translation of the HHIE-S that yields equivalent
      results to those obtained with the English version in bilingual Mexican
      Americans. The Spanish HHIE-S presented here is suitable for clinical use and
      research studies involving older Mexican Americans.

PMID- 9560076
TI  - Systems of care for older populations of the future.

PMID- 9560077
TI  - Geriatric nurse practitioners in long-term care: demonstration of effectiveness
      in managed care.
AB  - OBJECTIVE: This study was undertaken to review the impact of utilizing geriatric
      nurse practitioner/physician (GNP/ MD) teams on cost and utilization for a cohort
      of Medicare HMO enrollees residing in long-term care facilities. The results
      would be used by the organization for further development of the GNP Program.
      DESIGN: A 1-year retrospective data analysis on revenues and cost for 1077 HMO
      enrollees residing in 45 long term-care facilities. SETTING: Proprietary and not
      for-profit, licensed long term care facilities in the HMO's service area of
      central Massachusetts. Facilities in the study had both skilled (Medicare
      certified) and custodial beds. MEASUREMENTS: Data were collected retrospectively
      on overall cost, revenues, emergency department (ED) transfers, hospital, and
      subacute days. RESULTS: Of 1077 residents, 414 were cared for by GNP/MD teams
      compared with 663 by physicians alone. Acute care and ED costs were significantly
      lower for the GNP/MD-covered patients. There was a gain of $72 per resident per
      month (PRPM) with the GNP/MD-covered patients compared with a loss of $197 PRPM
      for physicians alone. There were no significant differences in ancillary services
      or prescriptions. CONCLUSION: The use of GNPs in collaboration with physicians
      reduced ED and acute care utilization costs as well as overall costs for a cohort
      of HMO enrollees in long-term care. This encouraged the HMO to support the
      concept that all long-term care HMO residents should be covered by GNP/MD teams.

PMID- 9560078
TI  - Preparing Canadian physicians for health care of older adults.

PMID- 9560079
TI  - Getting meaningful informed consent from older adults: a structured literature
      review of empirical research.
AB  - OBJECTIVES: To perform a structured literature review of the published empirical
      research on informed consent with older adults in order to make recommendations
      to improve the informed consent process and to highlight areas needing further
      examination. DESIGN: Relevant literature was identified by searching electronic
      databases (AGELINE, BIOETHICSLINE, CancerLit, Ethics Index, Health, LegalTrac,
      MEDLINE, PAIS International, PsycInfo, and Sociofile). Studies were included if
      they were reports of primary research data about informed consent and, if
      patients or other subjects were used, older subjects were included in the sample.
      Data related to the aspect of informed consent under study (recruitment, decision
      making capacity, voluntariness, disclosure of information, understanding of
      information, consent forms, authorization, and policies and procedures) were
      abstracted and entered into a specially designed database. MEASUREMENTS:
      Characterization of the population, age of subjects, setting, whether informed
      consent was being studied in the context of research or treatment, study design,
      the nature of outcome or dependent variables, independent variables (e.g.,
      experimental conditions in a randomized controlled trial or patient/subject
      characteristics in a nonrandomized comparison), and results according to the
      aspect of informed consent under study. RESULTS: A total of 99 articles met all
      the inclusion criteria and posed 289 unique research questions covering a wide
      range of aspects of informed consent: recruitment (60); decision making capacity
      (21); voluntariness (6); disclosure (30); understanding (139); consent forms (7);
      authorization (11); policies (13); and other (2). In the secondary analyses of
      numerous studies, diminished understanding of informed consent information was
      associated with older age and fewer years of education. Older age was also
      sometimes associated with decreased participation in research. Studies of
      disclosure of informed consent information suggest strategies to improve
      understanding and include a variety of novel formats (e.g., simplified,
      storybook, video) and procedures (e.g., use of health educators, quizzing
      subjects, multiple disclosure sessions). CONCLUSIONS: A systematic review of the
      published literature on informed consent reveals evidence for impaired
      understanding of informed consent information in older subjects and those with
      less formal education. Effective strategies to improve the understanding of
      informed consent information should be considered when designing materials,
      forms, policies, and procedures for obtaining informed consent. Other than
      empirical research that has investigated disclosure and understanding of informed
      consent information, little systematic research has examined other aspects of the
      informed consent process. This deficit should be rectified to ensure that the
      rights and interests of patients and of human subjects who participate in
      research are adequately protected.

PMID- 9560080
TI  - Heart failure: evaluation and treatment of patient's with left ventricular
      systolic dysfunction. Agency for Health Care Policy and Research (AHCPR).

PMID- 9560081
TI  - The Balanced Budget Act of 1997: implications for the practice of geriatric
      medicine.

PMID- 9560082
TI  - Outcomes-based quality improvement: reducing the data collection burden.

PMID- 9560083
TI  - On clinical diagnosis of congestive heart failure in older patients.

PMID- 9560084
TI  - Prescribing less than recommended doses may be acceptable for geriatric patients.

PMID- 9560085
TI  - Urinary incontinence in nursing home residents.

PMID- 9560086
TI  - After a major earthquake, stroke death occurs more frequently than coronary heart
      disease death in very old subjects.

PMID- 9560087
TI  - Risk factors determining mortality in older diabetics: a pilot study in Japanese
      patients.

PMID- 9560088
TI  - Weight loss precedes Alzheimer's disease symptoms: a case study.

PMID- 9560089
TI  - Patent ductus arteriosus in older people.

PMID- 9560090
TI  - Rescuing the doctor: swimming lessons for physician-educators.

PMID- 9560091
TI  - Intracranial tumors mimicking benign paroxysmal positional vertigo.
AB  - Benign paroxysmal positional vertigo is a common type of vertigo seen by the
      otolaryngologist; however, intracranial tumors can mimic benign paroxysmal
      positional vertigo in their presentation. A review of patients seen in the
      Department of Otolaryngology at The Ohio State University between July 1992 and
      August 1996 identified five patients with intracranial pathologic conditions
      mimicking benign paroxysmal positional vertigo. These patients were first seen
      with episodic vertigo associated with positional change. Failure of the symptoms
      to respond to the particle repositioning maneuver or the finding of associated
      auditory or neurologic symptoms prompted further evaluation by magnetic resonance
      imaging of the brain, which revealed intracranial pathologic conditions including
      two meningiomas, a vestibular schwannoma, a glioma, and a lipoma. These findings
      suggest that patients seen with symptoms like those of benign paroxysmal
      positional vertigo who do not show improvement after undergoing the particle
      repositioning maneuver or those who describe associated auditory or neurologic
      symptoms should have magnetic resonance imaging done to rule out intracranial
      pathologic conditions. Additionally, benign paroxysmal positional vertigo and
      intracranial tumors may coexist.

PMID- 9560092
TI  - Management of otitis media using Agency for Health Care Policy and Research
      guidelines. The Agency for Health Care Policy and Research.
AB  - Increased costs of managing otitis media and its complications may result from
      delays in diagnosis and treatment. The Agency for Health Care Policy and Research
      developed guidelines to assist in the management of chronic otitis media with
      effusion. We examined the medical care adherence to Agency for Health Care Policy
      and Research guidelines in 59 consecutive patients referred because of chronic
      otitis media with effusion and recurrent acute otitis media. Patient history and
      examination data were collected prospectively. In the group with chronic otitis
      media with effusion, the rate of adherence to Agency for Health Care Policy and
      Research guidelines was 0%; in those with recurrent acute otitis media, adherence
      was 5%. Delayed referral occurred in 34% of patients; 25% of patients were
      referred early. The average duration of effusion in patients with chronic otitis
      media with effusion was 5.2 months; the duration of recurrent acute otitis media
      immediately before referral was 9.3 months. Eighteen patients (47%) in the
      chronic otitis media with effusion group had a history of recurrent chronic
      otitis media with effusion spanning an average of 22.7 months. On referral,
      hearing loss was discovered in 92% of all patients, and in 69% the tympanogram
      was flat. The complication and sequelae rate was 49.1%, and speech delay was the
      most frequent at 16.9%. We conclude that in our study patients there is a
      significant referral delay, long history of chronic otitis media with effusion in
      patients before referral, high rate of hearing loss, and high complication rate.
      Continued efforts should be directed toward improving education of all clinicians
      so that diagnostic tools and timely otolaryngologic referral are better used.

PMID- 9560093
TI  - Resistance to biofilm formation on otologic implant materials.
AB  - New materials and coatings are now being developed to resist permanent bacterial
      contamination of implanted medical devices. This study exposed several styles of
      middle ear ventilation tube materials and coatings to high concentrations of
      Pseudomonas and Staphylococcus. Electron microscopy was then used to evaluate
      these tubes' resistance to bacterial biofilm formations. Ionized, processed
      silicone tubes were the only tubes resistant to Pseudomonas adhesion. Tubes that
      were made of fluoroplastic or that were ionized processed were very resistant to
      Staphylococcus contamination when compared with untreated silicone or silver
      oxide-treated silicone. This study suggests that ionized, coated fluoroplastic
      would be a highly effective tube material in preventing bacterial biofilm
      contamination of implanted ventilation tubes.

PMID- 9560094
TI  - Botulinum toxin decreases salivation from canine submandibular glands.
AB  - The objective of this study was to determine whether botulinum toxin types A and
      D reduced the production of saliva from the submandibular glands of 18 dogs. The
      left submandibular glands of 8 dogs were injected with increasing doses of
      botulinum type A toxin (range 10 to 70 units), and the left glands of 10 dogs
      were injected with botulinum type D toxin (50 or 100 units). The right gland of
      each dog was injected with equivalent volumes of saline solution to serve as
      control. Six days after the injection, the lingual nerve was electrically
      stimulated for 10 minutes (3 mAmp, 20 Hz). The resulting volume of saliva was
      collected and weighed. Overall, the glands injected with types A or D toxin
      produced significantly less saliva than comparable glands injected with saline
      solution. Six of 8 dogs injected with type A toxin showed a significant decrease
      in saliva production (range 10.1% to 19.2%, one-sided p value = 0.0375) when
      compared with the controls. Nine of 10 dogs injected with type D toxin
      demonstrated a highly significant reduction in saliva production (total average
      decrease = 60%, two-sided pvalue = 0.001) when compared with the controls. We
      concluded that intraglandular injections of botulinum toxin types A and D
      significantly reduced the production of saliva from canine submandibular glands.
      The potential applications of intraglandular injections of botulinum toxin are
      discussed.

PMID- 9560095
TI  - Current trends in laryngectomy rehabilitation: a survey of speech-language
      pathologists.
AB  - This study determined the perceptions of experienced speech-language pathologists
      regarding current practices in the speech rehabilitation of laryngectomy patients
      since the introduction of the tracheoesophageal puncture-voice prosthesis
      technique in 1980. The sample population consisted of 151 experienced speech
      language pathologists, or 43% of those who were sent questionnaires. The speech
      language pathologists ranked tracheoesophageal puncture-voice prosthesis as their
      most preferred speech rehabilitation method and the electrolarynx as their least
      preferred, even though the electrolarynx continues to be the most frequently used
      method. Variable use of the tracheoesophageal puncture procedure by
      otolaryngologists was reported, with only a small portion perceived as using it
      routinely. About 65% of the speech-language pathologists reported that more than
      half of the laryngectomy patients were being given choices among speech
      rehabilitation methods. Nearly 50% of the speech-language pathologists reported
      that fewer than six speech therapy sessions were necessary with tracheoesophageal
      puncture patients, whereas more than 20% reported the need for 10 sessions or
      more. Use of manual closure of the tracheostoma by tracheoesophageal puncture
      patients far outweighed their use of automatic speaking valves. Most speech
      language pathologists reported that they were involved in teams with
      otolaryngologists to determine patient suitability for tracheoesophageal puncture
      and to troubleshoot problems. Eighteen different categories of medical and speech
      production problems were reported.

PMID- 9560096
TI  - Fenretinide-induced apoptosis of human head and neck squamous carcinoma cell
      lines.
AB  - BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) has a high
      incidence of recurrence and associated second primary malignancy. The retinoid 13
      cis-retinoic acid has been shown to be effective as both a chemopreventive and
      chemotherapeutic agent for HNSCC, but often with treatment-limiting toxicity. The
      synthetic retinoid fenretinide (N-(4-hydroxyphenyl)retinamide) (HPR) has
      significant antiproliferative activity against a number of animal and human
      malignancies and has been used in clinical trials as a chemopreventive agent in
      patients with breast and prostate cancer and oral leukoplakia. HPR has been shown
      to have a toxicity profile lower than that for other retinoids used in clinical
      trials. PURPOSE: The aim of this study was to investigate the effect of HPR on
      the growth of HNSCC cell lines in vitro. METHODS: Four HNSCC cell lines (JHU-011
      SCC, JHU-020-SCC, JHU-022-SCC, and FaDu) were treated with a range of
      concentrations of HPR for various times. After HPR exposure, cell viability was
      determined by tetrazolium dye (MTT) colorimetric assay, comparing cell survival
      with that of untreated control cells. HPR-induced apoptosis was determined by
      flow-cytometric deoxyribonucleic acid cell-cycle analysis, ultrastructural
      analysis with electron microscopy, and deoxyribonucleic acid fragmentation
      detected by gel electrophoresis. RESULTS: HPR caused significant growth
      inhibition in three of the four HNSCC cell lines in a dose- and time-dependent
      fashion. In two cell lines (JHU-011-SCC, JHU-020-SCC) a significant
      antiproliferative effect was achieved between 1 and 2.5 micromol/L HPR after 72
      hours of treatment. By deoxyribonucleic acid cell-cycle analysis, electron
      microscopy, and gel electrophoresis, HPR was shown to induce apoptosis in the JHU
      011-SCC and JHU-020-SCC cell lines, but not in the FaDu cell line, which was
      insensitive to the growth inhibitory effect of HPR. CONCLUSIONS: This study has
      demonstrated that HPR reduces cell viability in HNSCC cells in vitro at
      clinically relevant doses, with the growth inhibition occurring through the
      induction of apoptosis.

PMID- 9560097
TI  - Leukotrienes C4 and D4 increase the ciliary beat frequency in human upper airway
      mucosa in vitro.
AB  - It has been suggested that leukotrienes C4 (LTC4) and D4 (LTD4) released from
      upper respiratory mucosa influence mucociliary transport during allergic
      reactions. We studied the in vitro effects of leukotrienes C4 and D4 on the
      ciliary beat frequency (CBF) of human adenoid explants over a 5-hour period.
      Tissue explants were cultured at 35 degrees C in Minimum Essential Medium Eagle
      (MEM). The CBF was measured using phase contrast microscopy and microphotometry.
      Measurements of CBF were recorded in medium alone and in medium containing LTC4
      or LTD4 at concentrations of 10(-8) and 10(-6) M. LTC4 and LTD4 increased CBF at
      concentrations of 10(-8) and 10(-6) M with increases of 20.51% +/- 2.69% and
      29.84% +/- 4.06%, respectively. To determine the specificity of the LTC4 and LTD4
      effects, the ciliated epithelium was treated with the specific leukotriene
      receptor antagonist LY-171,883 before administration of LTC4 and LTD4. LY-171,883
      (10(-6) M) significantly inhibited the ciliostimulatory effects of both
      leukotrienes. Our findings indicate that LTC4 and LTD4 increase CBF in vitro by
      activation of the LTD4 receptor.

PMID- 9560098
TI  - Analysis of short-term outcome after office-based laser-assisted
      uvulopalatoplasty.
AB  - To determine the short-term effectiveness and outcome of office-based laser
      assisted uvulopalatoplasty, a prospective statistically controlled study was done
      at the Department of Otolaryngology, Cleveland Clinic Florida. Thirty-eight
      consecutive snoring patients underwent a total of 98 laser-assisted
      uvulopalatoplasties, and data were gathered through examination, interview, and
      analog scales of snoring, pain, and other morbidity. In addition, a failure
      analysis was performed. Data were analyzed by descriptive statistics, confidence
      intervals, and adjusted analysis of variance (p < 0.008). Our results suggest
      that snoring decreased significantly around each laser-assisted uvulopalatoplasty
      treatment performed (4 to 8 weeks apart). Postoperative pain diminished after the
      first two laser-assisted uvulopalatoplasty treatments. The only morbidity in the
      series was the result of significant pain, causing 77% of laser-assisted
      uvulopalatoplasty failures.

PMID- 9560099
TI  - Cause of hoarseness in elderly patients.
AB  - Hoarseness is a common symptom in older individuals and may reflect a wide
      variety of pathologic, medical, physiologic, and/or functional causes. Although
      vocal fold atrophy is one of the more common reported findings in the elderly,
      inconclusive information is known about the differential diagnosis and cause of
      dysphonia in older individuals. The purpose of this investigation was to review
      the cause of hoarseness in all patients older than 65 years and to determine any
      correlation with advancing age and other demographic factors. Additionally, we
      wanted to determine the effect vocal pathology has on objective voice measures
      with advancing age. The two most common causes of hoarseness found in 393
      patients older than 65 years were vocal fold bowing and unilateral vocal fold
      paralysis, followed by benign vocal fold lesions, voice tremor, and spasmodic
      dysphonia. Although objective measures of vocal function were abnormal compared
      with reported normative data, they did not increase in severity with advancing
      age. Apparently, the compounding effect of age on underlying vocal pathology does
      not increase the severity of the vocal disturbance, at least as represented by
      objective voice measures. The high incidence of medical illnesses seen in this
      population also needs to be kept in mind because it may further affect the
      underlying voice disturbance. It might be interesting to compare data on the
      patients' perceptions of their vocal disturbance for each disorder as a function
      of age. It would also be helpful to know whether patients responded to treatment
      differentially based on age.

PMID- 9560100
TI  - Carbon dioxide laser surgery for snoring: results in 192 patients.
AB  - Laser-assisted uvulopalatoplasty has been introduced as an alternative to
      uvulopalatopharyngoplasty for treatment of snoring and potentially of obstructive
      sleep apnea syndrome. Between July 1994 and June 1996, 192 patients underwent 227
      laser-assisted uvulopalatoplasty procedures. Loud habitual snoring was evaluated
      in 42 women (21.8%) and 150 men (78.2%), who were then treated with laser
      assisted uvulopalatoplasty. Among the 192 patients (227 procedures), with ages
      from 18 to 81 years (mean 42.6 years), 15.6% (30 patients) had more than one
      laser-assisted uvulopalatoplasty treatment. In our series, 80 patients (42.1%)
      had a history of obstructive sleep apnea syndrome in addition to snoring. Laser
      assisted uvulopalatoplasty treatment in patients with loud snoring resulted in
      elimination of snoring in 61%, partial improvement of snoring in 26%, and no
      improvement in 13%. The overall success rate was 87%. The mean body mass index
      was significantly higher in the patients with no response after the operation
      (27.9 kg/m2) compared with that in the patients with a good response (25.9
      kg/m2). Obese (body mass index >30 kg/m2) patients were more likely to have no
      response to laser-assisted uvulopalatoplasty treatment of snoring than patients
      with an ideal body weight (body mass index <25 kg/m2) (p < 0.01). We conclude
      that the body mass index may be of significant value in the postoperative success
      rate of laser-assisted uvulopalatoplasty for the treatment of snoring.

PMID- 9560101
TI  - Interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating
      factor receptor expression in chronic sinusitis and response to topical steroids.
AB  - Chronic sinusitis and its associated eosinophilic infiltrate are believed to be
      mediated, at least in part, by the upregulation of Th-2 cytokines, including
      interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating
      factor (GM-CSF). Interleukin-4 is involved in IgE production and in eosinophil
      recruitment through upregulation of vascular cell adhesion molecule-1.
      Interleukin-5 and GM-CSF are involved in eosinophil growth and survival. The aim
      of this study was to investigate the expression of receptors for these cytokines
      in the sinus mucosa of subjects with chronic sinusitis. Using the technique of in
      situ hybridization to detect specific cytokine receptor messenger RNA, we studied
      the sinus mucosa of subjects with nonallergic chronic sinusitis, subjects with
      allergic chronic sinusitis, subjects with allergic chronic sinusitis treated with
      topical steroids, and normal controls. Our data demonstrate higher expression of
      interleukin-4 receptor in subjects with allergic chronic sinusitis than in
      controls (p < 0.001) and higher expression of interleukin-5 receptor in both
      subjects with nonallergic chronic sinusitis and subjects with allergic chronic
      sinusitis than in controls (p < 0.001, p < 0.001). The expression of interleukin
      4 receptor and interleukin-5 receptor was higher in subjects with allergic
      chronic sinusitis than in subjects with nonallergic chronic sinusitis (p <
      0.001). GM-CSF receptor expression was also found to be higher in subjects with
      allergic chronic sinusitis and subjects with nonallergic chronic sinusitis than
      in controls (p < 0.001, p < 0.001). In contrast to interleukin-4 receptor and
      interleukin-5 receptor, however, expression of GM-CSF receptor was higher in
      subjects with nonallergic chronic sinusitis than in subjects with allergic
      chronic sinusitis (p < 0.001). In subjects with allergic chronic sinusitis
      treated with topical corticosteroids, the expression of interleukin-4 receptor
      and interleukin-5 receptor messenger RNA levels was significantly lower than
      levels in patients with allergic chronic sinusitis who were not taking topical
      steroids (p < 0.001, p < 0.001). Steroid treatment had no effect on GM-CSF
      receptor messenger RNA expression. In conclusion, our data support a role for Th
      2 cytokine receptors in the pathophysiology of chronic sinusitis. Further, our
      data lend support to the theory that differential activation of distinct cytokine
      pathways mediates inflammation in chronic sinusitis depending on whether there is
      associated allergy. Finally, treatment with topical corticosteroids has been
      demonstrated in chronic sinusitis to downregulate receptors for interleukin-4 and
      interleukin-5.

PMID- 9560102
TI  - Intratumoral cisplatin/epinephrine-injectable gel as a palliative treatment for
      accessible solid tumors: a multicenter pilot study.
AB  - Intratumoral injections of cisplatin/epinephrine-injectable gel were administered
      weekly for 4 weeks in 45 patients with malignant tumors of various histologic
      types. Tumors were located on the skin and subcutaneous tissue primarily of the
      head, neck, and trunk, and on the tongue, oral pharynx, and esophagus. Patients
      were not candidates for surgery, radiation, or systemic chemotherapy. Each of the
      treated tumors (n = 82) was evaluated 2, 4, 8, and 12 weeks after the final
      injection. The initial dose of cisplatin was 1 mg/cm3 tumor volume, with
      escalation to 6 mg/cm3 allowed, depending on observed toxicities. The mean
      cumulative dose per patient for the four treatments ranged from 0.56 to 380 mg
      cisplatin. No dose-limiting cisplatin-related toxicities, such as nephrotoxicity,
      neurotoxicity, or ototoxicity, were observed. The overall objective tumor
      response rate was 50% (41 of 82), with 40% (33 of 82) complete responses and a
      median response duration of 160 days. Complete responses for adenocarcinoma and
      squamous cell carcinoma were 58% (21 of 36) and 38% (12 of 32), respectively.
      These results justified further clinical trials to evaluate the role of local
      chemotherapy with intratumoral cisplatin/epinephrine-injectable gel in the
      palliative treatment of patients with selected accessible solid tumors.

PMID- 9560103
TI  - Interleukin-6 expression in chronic sinusitis: colocalization of gene transcripts
      to eosinophils, macrophages, T lymphocytes, and mast cells.
AB  - Chronic sinusitis in allergic (ACS) and nonallergic (NCS) patients is
      characterized by persistent inflammation and subepithelial fibrosis of the sinus
      mucosa. The inflammatory infiltrate is rich in T lymphocytes,
      monocyte/macrophages, plasma cells, and eosinophils. Th2-type cytokines are
      thought to regulate inflammatory cell recruitment, activation, survival, and the
      release of tissue-damaging mediators. Interleukin-6 is a proinflammatory Th2-type
      cytokine that stimulates fibroblast proliferation and collagen synthesis.
      Expression of interleukin-6 has been reported in pulmonary fibrosis and a number
      of other conditions associated with fibrotic tissue changes. In vitro studies
      have indicated that interleukin-6 is produced by macrophages, T cells,
      eosinophils, mast cells, and other cell types. Here we examined interleukin-6
      messenger RNA and immunoreactivity in the sinus epithelium and subepithelium of
      subjects with ACS and NCS by in situ hybridization and immunocytochemistry,
      performed on sinus biopsy and polyp sections obtained from patients. Nasal
      turbinate biopsy specimens from normal volunteers were used as controls.
      Interleukin-6 messenger RNA and immunoreactivity were expressed by a
      significantly greater proportion of epithelial and subepithelial cells in ACS and
      NCS subjects than in normal controls. There was no difference in epithelial or
      subepithelial interleukin-6 expression between ACS and NCS patients.
      Colocalization studies revealed that macrophages, T cells, eosinophils, and mast
      cells are sources of interleukin-6 messenger RNA in ACS and NCS. The numbers of
      interleukin-6 messenger RNA-positive cells coexpressing immunoreactivity for the
      mast-cell marker were significantly greater in ACS than in NCS subjects. The
      results of this study suggest a role for interleukin-6 in the inflammatory
      response of chronic sinusitis.

PMID- 9560104
TI  - Long-term model of induced canine phonation.
AB  - Experimental induced phonation in the dog has been used in short-term studies by
      several investigators and has proved quite useful in laryngeal research. In this
      study a long-term canine phonation model is described that uses permanently
      implanted electrodes on the superior and recurrent laryngeal nerves. A serial
      induced phonation model has not been previously reported and is needed for
      laryngeal research in which voice results are a primary end point. Inexpensive,
      reliable, nontoxic electrodes were designed and fabricated. The laryngeal nerves
      were found to be quite susceptible to injury, necessitating a series of changes
      in electrode design. Electrode durability and laryngeal nerve viability improved
      with each design modification; the final design gave a recurrent laryngeal nerve
      viability rate of 100% at 6 weeks, 83% at 9 weeks, and 73% at 12 weeks. Induced
      phonation was successfully produced on a repeated basis by stimulating the
      recurrent laryngeal nerves while passing air through the larynx, in 22 (95.6%) of
      23 animals. Stimulation of the superior laryngeal nerves increased vocal fold
      length and tension but was not required for phonation. Technical aspects of
      chronic implantation and stimulation of the laryngeal nerves are discussed. The
      development and successful long-term implantation of electrodes on the laryngeal
      nerves and their use in repeated induced phonation have not been reported
      previously.

PMID- 9560105
TI  - Squamous cell carcinoma of the supraglottic larynx in a patient with Fanconi's
      anemia.

PMID- 9560106
TI  - Giant cell reparative granuloma of the temporal bone: case report and review of
      the literature.

PMID- 9560107
TI  - Radiation-induced malignant fibrous histiocytoma of the head and neck.

PMID- 9560108
TI  - The cochlear aqueduct: an important landmark in lateral skull base surgery.
AB  - The cochlear aqueduct (CA) is used as a landmark in lateral skull base surgery.
      In this study anatomic relationships between the CA and adjacent neurovascular
      structures were examined by dissecting 32 temporal bones. Observations of the
      relationship of the external opening (EO) of the CA with the ninth, tenth, and
      eleventh cranial nerves, inferior petrosal sinus (IPS), and intrapetrous carotid
      artery (ICA) were noted. In addition to the distance of the EO of the CA to the
      vertical portion of the ICA, the entire length of the CA and the width of the EO
      were also measured. The ninth nerve was the only structure lodged at the EO of
      the CA in 34.4% of bones. However, in 40.6% of bones only the IPS crossed the EO
      of the CA, although the ninth nerve was situated just anteroinferiorly in the
      vicinity of the EO. In 15.6% of bones it was possible to observe both the ninth
      nerve and the IPS crossing the EO. In 9.4% of bones the EO of the CA was found to
      be occupied by the tenth and eleventh nerves. It was also observed that the ICA
      was located anteriorly on the same sagittal plane with the EO in 15.6% of bones.
      It was concluded that although in 90% of cases the EO of the CA was in close
      relation with the ninth nerve, other structures such as the IPS, the tenth and
      eleventh cranial nerves, and the ICA were also at risk during drilling in this
      area because of their intimate relationships with the EO of the CA.

PMID- 9560109
TI  - Changes in laryngeal muscle activities during hypercapnia in the cat.
AB  - The larynx has three functions: phonation, airway protection, and respiration.
      Few studies have dealt with laryngeal respiratory function. To elucidate
      respiratory regulation by the larynx, we studied the changes in the activity of
      the intrinsic laryngeal muscles during hypercapnia in decerebrated cats. The
      electromyographic activities of the posterior cricoarytenoid (PCA) and
      thyroarytenoid (TA) muscles were recorded simultaneously with an electromyogram
      of the diaphragm, endotracheal pressure, and concentrations of O2 and CO2. The
      activity of the intrinsic laryngeal muscles during hypercapnia (end-tidal CO2, 8%
      to 10%) was analyzed in comparison with that during eucapnia. In hypercapnia,
      both the PCA and TA muscles increased their activities, and the endotracheal
      pressure during expiration was elevated to a higher level than that in eucapnia.
      TA muscle activities returned to the level during eucapnia after ligation of the
      common carotid arteries. These findings suggest that hypercapnia causes a further
      widening of the glottis during inspiration to decrease inspiratory resistance and
      a further narrowing of the glottis during expiration to prevent alveolar
      collapse. Thus it may be concluded that the larynx actively participates in
      respiratory regulation under the control of the brain stem through a process of
      peripheral inputs from the carotid receptors.

PMID- 9560110
TI  - Objective scaling of facial nerve function based on area analysis (OSCAR).
AB  - An objective scaling of facial nerve function based on area analysis (OSCAR) was
      developed using the variations of luminance produced by changes of facial
      expression. The presented method of scaling facial motions has the advantage of
      being continuous, objective, and reproducible. It is fast and simple to use.

PMID- 9560111
TI  - Vancomycin administration in continuous ambulatory peritoneal dialysis: the risk
      of ototoxicity.
AB  - A prospective study was undertaken in 16 patients with chronic renal failure on
      continuous ambulatory peritoneal dialysis, with 22 episodes of peritonitis
      treated with vancomycin, a known ototoxic agent. Twelve patients had one episode
      each, and four had recurrent peritonitis. Each treatment course consisted of two
      infusions of vancomycin (30 mg/kg body weight) in 2 L of peritoneal dialysate
      administered at 6-day intervals. Serum vancomycin analyzed by enzyme immunoassay
      showed a mean trough level of 11.00 microg/ml on day 6 and mean serum levels of
      33.8 and 38.6 microg/ml about 12 hours after administration on days 1 and 7,
      respectively. Similar levels, well within the therapeutic range, were encountered
      with repeated vancomycin therapy for recurrent episodes of peritonitis,
      suggesting that no changes occurred in the pharmacokinetic profile of the drug.
      Pure-tone audiometry, electronystagmography, and clinical assessment performed
      during each course of treatment showed no evidence of ototoxicity even on
      repeated courses of vancomycin therapy. The results suggest that vancomycin
      therapy when given in appropriate concentrations as a single therapeutic agent is
      both effective and safe. We believe, however, that vancomycin administered in
      combination with an aminoglycoside may produce ototoxic effects that may be
      greatly aggravated, possibly because of synergism.

PMID- 9560112
TI  - Tension pneumocephalus after frontal sinus gunshot wound.

PMID- 9560113
TI  - Dermoid cyst of the floor of the mouth.

PMID- 9560114
TI  - Healing of complex tracheostomy wounds.

PMID- 9560115
TI  - The inflammatory response to open tension-free inguinal hernioplasty versus
      conventional repairs.
AB  - BACKGROUND: The tension-free inguinal hernioplasty is now a popular method
      because of less postoperative disability and low recurrence rate. The laboratory
      evaluation of the inflammatory response to the injury is an objective approach to
      determine the stress status of a surgical procedure. The aim of this study is to
      evaluate and to compare inflammatory responses to open tension-free and
      conventional repairs of inguinal hernias. METHODS: Forty-eight male patients with
      primary indirect inguinal hernias were treated with elective operations, and
      separated into three groups according to surgical procedure: 12 pediatric
      patients treated with dissection of hernia sac in group 1, 16 adult patients with
      open tension-free hernioplasty in group 2, and 20 adult patients with
      conventional repairs in group 3. Ten healthy adult volunteers formed group 4 as
      control. The repair was performed with polypropylene mesh and suture as the
      Lichtenstein technique in group 2, and with polypropylene suture as one of
      Bassini, McVay, or Shouldice techniques in group 3. The inflammatory response was
      evaluated with serum interleukin-6 (IL-6) levels at 12 hours and serum C-reactive
      protein (CRP) levels at 48 hours postoperatively. Serum levels of IL-6 and CRP
      were measured in group 4 as control. Patient characteristics, operating time, and
      IL-6 and CRP levels were compared among the four groups. RESULTS: There were no
      significant differences in mean age and operating time between the two groups of
      adult patients with hernia repair. Mean serum IL-6 levels of 12.1 +/- 5.2 and 8.2
      +/- 2.7 pg/mL, and CRP levels of 34.3 +/- 13.8 and 7.5 +/- 4 mg/L in pediatric
      and control groups, respectively, were significantly lower than in the other two
      hernia groups. Mean serum IL-6 levels were 58.9 +/- 25.4 pg/mL in group 2
      (tension-free repair) and 44.3 +/- 18.1 pg/mL in group 3 (conventional repair) (P
      > 0.05). Mean serum CRP levels were 111.3 +/- 41.3 and 83 +/- 43.2 mg/L in groups
      2 and 3, respectively (P > 0.05). The differences not being statistically
      significant, a similar and considerable inflammatory response was noted in
      patients with either prosthetic mesh repair or with conventional repairs of
      indirect inguinal hernias. CONCLUSIONS: The reinforcement of the posterior wall
      of the inguinal canal induces significant cytokine response regardless of tension
      free or conventional repair. Open tension-free hernioplasty offered no advantages
      over conventional repairs from the standpoint of the inflammatory and acute phase
      response.

PMID- 9560116
TI  - A comparison of adrenalectomy with other resections for metastatic cancers.
AB  - BACKGROUND: Although adrenal metastases were once considered incurable, recent
      anecdotal reports recommend adrenalectomy for isolated metastases. METHODS:
      Computerized files of all US Department of Veterans Affairs (DVA) hospital
      admissions and deaths from 1988 to 1994 identified patients undergoing isolated
      adrenal resections, and hospitalization records were obtained. Patients without a
      death record were assumed to be alive. RESULTS: In 47 patients with adrenalectomy
      for metastases, only 5 patients did not die within 3 years: 2 each had
      metachronous renal or colorectal metastases, and 1 had a pulmonary primary.
      Thirteen patients with other primary sites all expired within 3 years. Operative
      mortality was 4% in these 47 patients and also in 706 other adrenalectomies
      without metastases. CONCLUSIONS: Adrenalectomy for metastatic carcinoma in the
      DVA was safe, with a projected 5-year survival rate (13%) that is significantly
      inferior (P < or = 0.05) to resections for colorectal metastases to lung (36%) or
      liver (26%), but superior to brain (none).

PMID- 9560117
TI  - Restoration of anal sphincter function by single-stage dynamic graciloplasty with
      a modified (split sling) technique.
AB  - BACKGROUND: Controlled muscle fiber conversion by electrostimulation makes
      transformation of fast twitching type II muscle fibers to slow twitching type I
      fibers possible, which gives skeletal muscles the capacity for tetanic
      contraction. This phenomenon has been recently applied in the so-called "dynamic
      graciloplasty" to restore function of an insufficient or excised anal sphincter.
      This paper describes our results with this method in patients with fecal
      incontinence or following an abdomino-perineal resection (APR) of the anorectum.
      METHODS: From April 1992 through April 1997, 28 patients (12 women and 16 men)
      were treated by dynamic graciloplasty. The median age was 53.5 years (range 16 to
      79). Indications were as follows: APR + synchronous restoration of the excised
      sphincter by graciloplasty (n = 12); total anorectal reconstruction (TAR)
      following APR in the past (n = 6); Patients with acquired fecal incontinence (n =
      4); and Congenital atresia (n = 6). Muscle transposition, implantation of
      stimulation electrodes and pulse generator were done as a single-stage procedure,
      the "neosphincter" was wrapped in a modified technique (split-sling technique).
      Muscle transformation was performed by controlled neuromuscular stimulation
      during 8 weeks (from 1992 to 1995) and 4 weeks (since 1996), respectively.
      RESULTS: No postoperative mortality (90 days) was observed in either group. In
      our early experience, rectal injury occurred in 4 patients as the most prominent
      complication. Evaluation of the functional outcome showed the best results in
      patients operated either for congenital of acquired incontinence who achieved a
      continence for solids and liquids or solids alone, respectively (1 or 2 according
      to Williams' score) in 90%, while patients following APR showed a satisfying
      outcome (continence for solids and liquids, solids alone or with occasional
      episodes for liquids) in only 55.5%. In patients following APR, defecation
      disorders turned out to be the most prominent functional problem and had to be
      treated by enemas. CONCLUSION: In this series, we have been able to perform
      dynamic graciloplasty as a one-stage procedure using a modified muscle wrap
      (split-sling-technique) thus reducing the time period until continence could be
      achieved to 7 weeks. We found the appropriate tension of the muscle wrap
      essential to prevent direct injury to the rectum as it was seen in our early
      experience. For this reason, we have introduced a modified device to perform
      intraoperative anal manometry and to measure pressures created by the
      neosphincter objectively.

PMID- 9560118
TI  - Initial clinical experience with colonic stent placement.
AB  - BACKGROUND: The purpose of this study is to review initial experience with a
      colonic stent as an alternative to colostomy in patients with colonic
      obstruction. METHODS: Ten patients diagnosed with acute colonic obstructions from
      both benign and malignant causes underwent stent placement. Self-expandable
      metallic stents were deployed using fluoroscopic guidance. Patients were followed
      up clinically until removal of the stent or death. RESULTS: Nine of the 10
      patients who underwent colonic stent placement achieved clinical decompression
      within 6 hours. Six patients underwent standard mechanical bowel preparation and
      elective resection of obstructing lesions. The other 4 patients received stent
      placement for palliative purposes. Complications included 4 cases of migration
      and 1 death. Migrated stents in the rectum were easily retrieved and replaced
      using fluoroscopic techniques. There were no perforations. CONCLUSION: Placement
      of self-expandable metallic stents for acute colonic obstructions may allow
      patients to undergo elective surgical resection avoiding possible colostomy.

PMID- 9560119
TI  - The type of K-ras mutation determines prognosis in colorectal cancer.
AB  - BACKGROUND: Mutations involving the oncogene K-ras in colorectal cancer may be
      related to tumor aggressiveness. However, the value of K-ras gene determination
      as a prognostic marker has not been clearly established. PATIENTS AND METHODS:
      The results from 98 patients recruited in a prospective study analyzing the
      effect of a K-ras mutation as a prognostic factor in colorectal cancer are
      reported. RESULTS: Disease-free (P = 0.02) and overall survival (P = 0.03) were
      significantly reduced for patients harboring a K-ras mutation. Two specific
      mutations demonstrated a significantly increased risk of disease recurrence,
      namely, 12-TGT (P = 0.04) and 13-GAC substitutions (P = 0.002). Patients with
      either of these substitutions had a 2-year disease-free survival rate of 37%
      compared with that of 67% for the group of patients harboring any other mutation
      type or a wild-type status (P = 0.01). CONCLUSIONS: The results herein presented
      suggest that K-ras acts as a prognostic factor in colorectal cancer and that this
      effect is probably related to a limited number of defined mutations.

PMID- 9560120
TI  - Comparison of endoscopic retrograde and magnetic resonance
      cholangiopancreatography in the surgical diagnosis of pancreatic diseases.
AB  - BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is a newly
      developing noninvasive examination of the biliopancreatic trees. Roles of MRCP in
      the diagnosis of pancreatic diseases have not been scrutinized. METHODS:
      Endoscopic retrograde cholangiopancreatography (ERCP) and MRCP were reviewed in
      52 Japanese patients with various pancreatic diseases and 6 patients with normal
      pancreas to compare their diagnostic usefulness and limitation. RESULTS: In those
      with normal pancreas, only the main pancreatic duct was visualized by MRCP, while
      both the main pancreatic and branch ducts were clearly delineated by ERCP. In 3
      patients with serous cystadenoma, the tumor was not visualized by ERCP, whereas
      it was visible as a high-intensity mass on MRCP. Of 18 patients with a "mucin
      hypersecreting" tumor of the branch type, MRCP demonstrated cystically dilated
      branch ducts in all, while ERCP failed to visualize the dilated ducts in 6
      patients. However, the details of the cystic lesions (mural nodule, communication
      with the main pancreatic duct) were more exactly demonstrated by ERCP than MRCP.
      In 5 patients with a mucin hypersecreting tumor of the main pancreatic duct type,
      the dilated main pancreatic duct and the presence of mural nodules were similarly
      demonstrated both by ERCP and MRCP. In 12 patients with pancreatic
      adenocarcinoma, indirect findings were similarly demonstrated both by ERCP and
      MRCP, ie, stenosis (4 patients) and obstruction (8) together with dilation of the
      main pancreatic duct (9). In 3 patients, the center of the mass showed high
      intensity on MRCP, suggesting the secondary change of pancreatic carcinoma. In 8
      patients with obstruction of the main pancreatic duct due to carcinoma, the
      distal pancreatic duct was visualized by MRCP but not by ERCP. In 9 patients who
      had undergone pylorus-preserving or standard pancreatoduodenectomy, follow-up
      MRCP was obtainable in all examined and displayed the main pancreatic duct.
      CONCLUSIONS: MRCP plays a complementary role in the surgical diagnosis of
      pancreatic disorders and is especially useful to examine the pancreatic duct
      after pancreatoduodenectomy.

PMID- 9560122
TI  - Limb salvage for streptococcal gangrene of the extremity.
AB  - BACKGROUND: Extremity soft tissue infections from group A, beta-hemolytic
      streptococcus frequently culminate in amputation. This study compares our
      protocol for limb salvage with expected results. METHODS: Patients with extremity
      streptococcal gangrene treated from 1989 to 1995 were reviewed. The management
      protocol mandated immediate, radical excision of involved skin and subcutaneous
      tissue, with preservation of fascia. Patients were managed in the burn unit, and
      wounds were covered with split-thickness skin grafts. Amputation rate and
      mortality were measured. RESULTS: Fourteen cases of extremity streptococcal
      gangrene were identified. Delay to surgical referral was 5 days. Eleven (79%)
      patients were septic. Ten (71%) were managed with a single debridement before
      grafting. Limb salvage was 93% (13 of 14). One patient (7%) died on day 150 from
      acute myelogenous leukemia. CONCLUSIONS: Delay in referral of extremity
      streptococcal gangrene is common, contributing to a high incidence of sepsis. Our
      management protocol of a single, radical debridement with preservation of fascia
      maximizes limb salvage and survival.

PMID- 9560121
TI  - Effects of aging on the functional outcome of coloanal anastomosis with colonic J
      pouch.
AB  - BACKGROUND: Many low rectal cancers can be treated radically by proctectomy with
      total mesorectal excision followed by colonic J-pouch anal anastomosis (CPAA). In
      elderly patients, the fear of poor function might reduce indications for CPAA in
      favor of abdomino-perineal excision with end stoma. METHODS: Among 198 patients
      with CPAA operated on for low rectal cancer between 1984 and 1992, 20 patients
      over 75 years old were alive without recurrence at the time of telephone
      interview (July 1995). Minimal follow-up was 3 years (mean 8) for all patients.
      Their functional results were compared with those of 37 younger patients operated
      consecutively during the last 5 years of the study period. RESULTS: The two
      groups were well matched for gender, tumor distance from the anal verge,
      histologic staging, and use of adjuvant radiotherapy. Follow-up was longer in the
      elderly group than in the young group (96 versus 63 months, respectively). The
      elderly group had a median of 1 bowel movement per day and the young group a
      median of 1.5 (P = 0.13). The presence of irregular intestinal transit was
      reported in 48% of the aged and in 35% of the young group (P = 0.6), but
      fragmented defecation was less frequent (25% versus 47%, respectively; P = 0.15).
      Urgency was noted, respectively, in 15% and 22% of elderly and young patients (P
      = 0.7) and constipation in 40% and 22% (P = 0.2). Incontinence for feces (15%)
      and for flatus (40%) in elderly were not significantly different from the younger
      group (14% and 46%, P = 1.0 and P = 0.8, respectively). Laxatives were used in
      32% of elderly and 17% of young patients (P = 0.3). CONCLUSION: Functional
      outcome may be good to excellent in elderly patients after CPAA and compares well
      with that obtained in younger patients. Constipation, however, may be more
      frequent in the elderly. Age is not a contraindication for CPAA if the sphincter
      tone is clinically normal.

PMID- 9560123
TI  - Biliary tract cancer accompanied by anomalous junction of pancreaticobiliary
      ductal system in adults.
AB  - BACKGROUND: Anomalous junction of the pancreaticobiliary ductal system (AJPBDS)
      is a congenital anomaly in which the junction is located outside the duodenal
      wall. Recently, attention has been focused on the high incidence of malignancy in
      this anomaly. The purpose of this study was to clarify the clinicopathological
      features of this anomaly and to determine the appropriate surgical approach for
      biliary tract cancer associated with AJPBDS. METHODS: The data for 38 patients
      with AJPBDS, including 14 who had been treated for biliary tract cancer (2 with
      bile duct cancer and 12 with gallbladder cancer), were retrospectively reviewed.
      We assessed the clinical features, characteristics of the tumor, operative
      procedure, and outcome for each patient. RESULTS: The incidence of malignancy in
      AJPBDS was 17.8% (2 patients with bile duct cancer and 3 with gallbladder cancer)
      in the bile duct dilatation group (n = 28) and 90% (9 patients with gallbladder
      cancer) in the no-dilatation group (n = 10) . The mean length of the common
      channel was 24.7 mm (range 20 to 35 mm) . Resection with lymphadenectomy was
      performed in 9 (64.3%) of 14 patients, and curative resection in 5 of these 9
      patients. Ten (71%) of the 14 patients had lymph node involvement noted either at
      the time of initial diagnosis or at surgery. The incidence of lymph node
      metastasis was closely related to the depth of tumor involvement. Ten patients
      died of recurrence or primary cancer, from 3 to 30 months after operation. Four
      patients are still alive without recurrent disease from 2.5 to 13 years after
      operation. CONCLUSION: For patients with AJPBDS without bile duct dilatation,
      prophylactic cholecystectomy is recommended even if no malignant lesion is found
      in the gallbladder because of the high incidence of gallbladder cancer and the
      poor prognosis. Both early detection and curative resection of the tumor are
      essential for successful treatment of biliary tract cancer.

PMID- 9560124
TI  - Regulation of albumin mRNA and its promoter-binding nuclear factors under
      different perioperative nutritional methods in hepatectomized rats.
AB  - BACKGROUND: Regulation of perioperative albumin synthesis under parenteral (PN)
      and enteral (EN) nutrition was investigated. METHODS: Rats were divided into PN
      and EN groups. Both groups received the same regimen of artificial nutrition for
      7 days and then underwent 70% hepatectomy. Serum albumin and mRNA levels of
      albumin and its promoter-binding nuclear factors (C/EBPalpha, beta, and DBP) were
      measured. RESULTS: Serum albumin and albumin mRNA in the PN group were
      significantly lower than those in the EN group at 72 hours after hepatectomy.
      Preoperative and postoperative DBP and C/EBPalpha mRNA levels in the EN group
      were significantly higher than those in the PN group. CONCLUSION: Serum albumin
      was well maintained by EN after hepatectomy owing to an early recovery of albumin
      mRNA level and its nuclear factor mRNA levels (C/EBPalpha and DBP). Compared with
      PN, EN is a more advantageous from of perioperative nutrition as pertains to
      albumin synthesis.

PMID- 9560125
TI  - Litmus paper helps detect potential pancreatoenterostomy leakage.
AB  - BACKGROUND: Leakage of pancreatoenterostomy remains as a serious and fatal
      complication after pancreatectomy. Several risk factors have been reported, ie,
      normal pancreatic parenchyma, small pancreatic duct, a large amount of
      intraoperative blood loss, management of the cut surface of the pancreas, and the
      presence of preoperative jaundice. Transected pancreatic ductules on the cut
      surface of the pancreas that are not drained into the main pancreatic duct after
      pancreatectomy are one of the risks. The pancreatic juice is alkaline and turns
      red litmus to blue. METHODS: In order to detect the transected pancreatic
      ductules on the cut surface of the pancreas, red litmus paper is applied to the
      cutting surface of the pancreas after stimulation of secretin. RESULTS:
      Nondrained, transected pancreatic ductules on the cut surface of the pancreas can
      be detected as blue spots on the red litmus paper. The corresponding areas to the
      blue spots can be transfixed with sutures to close the nondrained and transected
      pancreatic ductules. CONCLUSION: Litmus paper can be expected to detect
      pancreatoenterostomy leakage after pancreatectomy.

PMID- 9560126
TI  - Segments I and IV resection as a new approach for hepatic hilar
      cholangiocarcinoma.
AB  - Major hepatic resection for biliary tract carcinoma with obstructive jaundice has
      been reported on as bringing about high surgical morbidity and mortality rates.
      It has been also revealed that the extent of hepatic resection is closely
      associated with the occurrence of postoperative complications. Therefore, hepatic
      resection, limited as much as possible to what is necessary for curative
      resection, should be performed according to cancer extent. We performed a new
      surgical approach in 3 patients with hepatic hilar cholangiocarcinoma that
      included total resection of hepatic segments I and IV (by Couinaud's
      classification) and bile duct resection with hepaticojejunostomy of 4 to 6
      intrahepatic bile duct stumps. All patients underwent curative surgical
      resections and were discharged within 6 weeks after surgery, without any serious
      complications. This limited resection of hepatic segments I and IV could be an
      effective radical surgical procedure for hepatic hilar cholangiocarcinoma, to
      avoid the occurrence of postoperative liver failure.

PMID- 9560127
TI  - Laparoscopic appendectomy does not change the incidence of postoperative
      infectious complications.
AB  - BACKGROUND: It is not clear whether the laparoscopic approach does decrease the
      incidence of postoperative infectious complications after appendectomy. METHODS:
      One hundred sixty-nine patients were randomized, 87 with laparoscopic (LA) and 82
      with open appendectomy (OA). Patients in the OA group had a McBurney incision; LA
      was performed in the lithotomy position. RESULTS: Acute appendicitis was
      confirmed in 75% of patients. The appendix was perforated in 5 patients of the LA
      versus 2 patients of the OA group. No conversion to the open procedure was
      necessary. The median operating time was 35 minutes in the LA group and 31
      minutes in the open group (P = 0.58). The median postoperative hospital stay was
      shorter after laparoscopic than after open surgery (3 days versus 4 days, P =
      0.026), whereas the time required for return to work was not significantly
      different (14 versus 15 days). There were 5 (6%) patients with superficial wound
      infection following LA and 6 (7%) after OA (P = 0.67). Intra-abdominal fluid
      collections were found in 2 (2%) patients following LA and 3 (4%) patients
      following OA (P = 0.60). In the LA group, 3 patients presented with intra
      abdominal hemorrhage and another 3 developed a paralytic ileus that was treated
      conservatively. CONCLUSIONS: Laparoscopic appendectomy is as safe and as
      effective as the open procedure; however, it does not decrease the rate of
      postoperative infectious complications.

PMID- 9560128
TI  - The nature and fate of categorical surgical residents who "drop out".
AB  - BACKGROUND: Little is known about the fate of categorical surgical residents who
      leave a program or if they differ from those who successfully complete a program.
      METHODS: Matching into separate categorical and preliminary categories with
      elimination of the pyramid began in 1982. The files of all categorical residents
      matched between 1982 and 1995 were reviewed for demographic and scholastic data.
      Drop-outs were compared with the residents who completed the program and with the
      current house staff. All residents have been followed up to the present. RESULTS:
      Between 1982 and 1996, 19 of 88 (22%) categorical residents who matched into the
      program left voluntarily. Eleven of 63 (17%) were male and 8 of 25 (32%) female
      (P = 0.12; test of proportions-Z = -1.55). They entered both surgical and
      nonsurgical fields. The major reasons for leaving were related to life-style
      issues. Their academic credentials are very similar to those who remained.
      CONCLUSIONS: The drop-out rate of categorical surgical residents is significant,
      and replacing them is not easy. We have not identified any characteristics that
      might predict attrition.

PMID- 9560129
TI  - Cytotoxicity of electro-surgical smoke produced in an anoxic environment.
AB  - BACKGROUND: The effect on cell viability of smoke produced during high-frequency
      electro-surgery has not been previously reported. The aim of this study was to
      produce smoke in vitro, in a closed environment similar to that encountered in
      minimal access surgery, and to test its cytotoxic effects on cultured cells.
      METHODS: Pig liver was cut repeatedly with an electro-surgical hook knife, and
      the smoke generated was collected and equilibrated with cell culture medium. MCF
      7 human breast carcinoma cells were exposed briefly to various dilutions of this
      medium and tested for clonogenicity. RESULTS: Electro-surgical smoke produced in
      a helium environment reduced the clonogenicity of the MCF-7 human breast
      carcinoma cells in a dose-dependent manner, falling to 30% when the cells were
      exposed to undiluted medium for 15 minutes. CONCLUSIONS: We conclude that electro
      surgical smoke is cytotoxic. The sublethal effects at lower dilutions are
      currently being investigated.

PMID- 9560130
TI  - Clinicopathological analysis of local spread of carcinoma of the tongue.
AB  - BACKGROUND: The aims of the study are three-dimensional analysis of mode and
      distance of local spread of oral tongue carcinoma. METHODS: The glossectomy
      specimens were examined in the coronal plane in 3 mm thickness section. RESULTS:
      There were 50 glossectomy specimens. The maximum spread was 1.8 cm. Ninety-six
      percent of specimens had local spread within 1.2 cm. The distance of spread was
      not correlated with tumor size, including the diameter, depth, and volume. The
      incidence of local recurrence was 27% with positive histological margin.
      Perineural infiltration was the most important prognostic factor for local
      recurrence and survival. CONCLUSIONS: A minimum of 1.5-cm surgical resection
      margin is recommended. A smaller margin is not recommended as it has significant
      risk of local recurrence. A maximum of 2-cm surgical resection margin is
      recommended; larger margins will increase the surgical morbidity without a
      significant advantage of local control.

PMID- 9560131
TI  - Menstrual timing of breast cancer surgery.
AB  - PURPOSE AND DESIGN: This is a critical review of the growing body of data, 32
      retrospective studies of the outcomes of 9,665 women published since 1989,
      relevant to the possibility that the timing of primary breast cancer resection
      within the menstrual cycle impacts breast cancer recurrence and/or spread and
      patient survival. This article evaluates and contrasts the adequacy of
      information and data analysis presented in each publication. The overall purpose
      of this exercise is to rigorously determine the relative strength of the
      hypothesis that the menstrual cycle timing of operation impacts outcome and,
      thereby, to determine whether or not a specific change in the practice of breast
      surgical oncology can be recommended. RESULTS: The single most completely
      reported and thoroughly analyzed series, involving 1,175 young women, indicates
      that surgical resection timing is likely to be relevant to outcome. Seven
      additional high-quality studies involving 2,864 women have been most completely
      reported. While two of these eight find no impact, six (75%) of these studies
      find that breast cancer outcome is affected by operative timing. Nine of the
      remaining 24 less-complete studies report a statistically significant effect of
      operative timing. Among these 15 studies of the fates of more than 5,000 women,
      the opportune menstrual cycle phase almost invariably includes the putative
      luteal phase. A large number of retrospective studies of widely varying quality
      find no outcome difference as a function of resection timing. The adequacy of
      design of each of four ongoing prospective studies is found lacking. CONCLUSIONS:
      Although it is likely that the menstrual cycle phase of operation is relevant to
      outcome, the nature of the available data cannot allow a clear recommendation of
      precisely when to operate. It is, therefore, concluded that current retrospective
      data are inadequate to recommend an immediate change in practice. Prospective
      studies of this potentially important question are essential. The prospective
      trials initiated to date will not be able to definitively answer this question
      because of inadequate chronobiological design. The minimal requirements for
      adequate prospective study are delineated.

PMID- 9560132
TI  - The complex realities of sharing genetic assets.

PMID- 9560133
TI  - Ex-UN AIDS chief is blasted for remarks on vaccine strategy.

PMID- 9560134
TI  - South African drugs agency to be replaced.

PMID- 9560135
TI  - Peer review cuts power of Italy's 'barons'.

PMID- 9560136
TI  - British BSE reckoning tells a dismal tale.

PMID- 9560137
TI  - When rhetoric hits reality in debate on bioprospecting.

PMID- 9560138
TI  - India seeks tighter controls on germplasm.

PMID- 9560139
TI  - Social equity versus private property: striking the right balance.

PMID- 9560140
TI  - Brazil's scientists warn against 'nationalistic' restrictions.

PMID- 9560141
TI  - A formula for indigenous involvement.

PMID- 9560142
TI  - Old scores surface as African states face new opportunities.

PMID- 9560143
TI  - Numbers of lab animals questioned.

PMID- 9560144
TI  - The centenarian Golgi apparatus.

PMID- 9560145
TI  - Putting the parkin into Parkinson's.

PMID- 9560146
TI  - Worlds in common through NF-kappaB.

PMID- 9560147
TI  - Computing. Parallel thinking.

PMID- 9560148
TI  - Signal transduction. Taking the Rap.

PMID- 9560149
TI  - Hesse-Honegger's hand-work.

PMID- 9560150
TI  - Vitamin C exhibits pro-oxidant properties.

PMID- 9560151
TI  - Regulatory factor linked to late-onset diabetes?

PMID- 9560152
TI  - Chemokines and leukocyte traffic.
AB  - Over the past ten years, numerous chemokines have been identified as attractants
      of different types of blood leukocytes to sites of infection and inflammation.
      They are produced locally in the tissues and act on leukocytes through selective
      receptors. Chemokines are now known to also function as regulatory molecules in
      leukocyte maturation, traffic and homing of lymphocytes, and the development of
      lymphoid tissues.

PMID- 9560153
TI  - Essential role of mouse telomerase in highly proliferative organs.
AB  - We have investigated the role of the enzyme telomerase in highly proliferative
      organs in successive generations of mice lacking telomerase RNA. Late-generation
      animals exhibited defective spermatogenesis, with increased programmed cell death
      (apoptosis) and decreased proliferation in the testis. The proliferative capacity
      of haematopoietic cells in the bone marrow and spleen was also compromised. These
      progressively adverse effects coincided with substantial erosion of telomeres
      (the termini of eukaryotic chromosomes) and fusion and loss of chromosomes. These
      findings indicate an essential role for telomerase, and hence telomeres, in the
      maintenance of genomic integrity and in the long-term viability of high-renewal
      organ systems.

PMID- 9560154
TI  - Dissociation of the neural correlates of implicit and explicit memory.
AB  - One presentation of a word to a subject is enough to change the way in which the
      word is processed subsequently, even when there is no conscious (explicit) memory
      of the original presentation. This phenomenon is known as implicit memory. The
      neural correlates of implicit memory have been studied previously, but they have
      never been compared with the correlates of explicit memory while holding task
      conditions constant or while using a procedure that ensured that the neural
      correlates were not 'contaminated' by explicit memory. Here we use scalp-recorded
      event-related brain potentials to identify neural activity associated with
      implicit and explicit memory during the performance of a recognition memory task.
      Relative to new words, recently studied words produced activity in three
      neuroanatomically and functionally dissociable neural populations. One of these
      populations was activated whether or not the word was consciously recognized, and
      its activity therefore represents a neural correlate of implicit memory. Thus,
      when task and memory contamination effects are eliminated, the neural correlates
      of explicit and implicit memory differ qualitatively.

PMID- 9560155
TI  - A cortical representation of the local visual environment.
AB  - Medial temporal brain regions such as the hippocampal formation and
      parahippocampal cortex have been generally implicated in navigation and visual
      memory. However, the specific function of each of these regions is not yet clear.
      Here we present evidence that a particular area within human parahippocampal
      cortex is involved in a critical component of navigation: perceiving the local
      visual environment. This region, which we name the 'parahippocampal place area'
      (PPA), responds selectively and automatically in functional magnetic resonance
      imaging (fMRI) to passively viewed scenes, but only weakly to single objects and
      not at all to faces. The critical factor for this activation appears to be the
      presence in the stimulus of information about the layout of local space. The
      response in the PPA to scenes with spatial layout but no discrete objects (empty
      rooms) is as strong as the response to complex meaningful scenes containing
      multiple objects (the same rooms furnished) and over twice as strong as the
      response to arrays of multiple objects without three-dimensional spatial context
      (the furniture from these rooms on a blank background). This response is reduced
      if the surfaces in the scene are rearranged so that they no longer define a
      coherent space. We propose that the PPA represents places by encoding the
      geometry of the local environment.

PMID- 9560156
TI  - Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
AB  - Parkinson's disease is a common neurodegenerative disease with complex clinical
      features. Autosomal recessive juvenile parkinsonism (AR-JP) maps to the long arm
      of chromosome 6 (6q25.2-q27) and is linked strongly to the markers D6S305 and
      D6S253; the former is deleted in one Japanese AR-JP patient. By positional
      cloning within this microdeletion, we have now isolated a complementary DNA done
      of 2,960 base pairs with a 1,395-base-pair open reading frame, encoding a protein
      of 465 amino acids with moderate similarity to ubiquitin at the amino terminus
      and a RING-finger motif at the carboxy terminus. The gene spans more than 500
      kilobases and has 12 exons, five of which (exons 3-7) are deleted in the patient.
      Four other AR-JP patients from three unrelated families have a deletion affecting
      exon 4 alone. A 4.5-kilobase transcript that is expressed in many human tissues
      but is abundant in the brain, including the substantia nigra, is shorter in brain
      tissue from one of the groups of exon-4-deleted patients. Mutations in the newly
      identified gene appear to be responsible for the pathogenesis of AR-JP, and we
      have therefore named the protein product 'Parkin'.

PMID- 9560157
TI  - Disruption and sequence identification of 2,000 genes in mouse embryonic stem
      cells.
AB  - The dramatic increase in sequence information in the form of expressed sequence
      tags (ESTs) and genomic sequence has created a 'gene function gap' with the
      identification of new genes far outpacing the rate at which their function can be
      identified. The ability to create mutations in embryonic stem (ES) cells on a
      large scale by tagged random mutagenesis provides a powerful approach for
      determining gene function in a mammalian system; this approach is well
      established in lower organisms. Here we describe a high-throughput mutagenesis
      method based on gene trapping that allows the automated identification of
      sequence tags from the mutated genes. This method traps and mutates genes
      regardless of their expression status in ES cells. To facilitate the study of
      gene function on a large scale, we are using these techniques to create a library
      of ES cells called Omnibank, from which sequence-tagged mutations in 2,000 genes
      are described.

PMID- 9560158
TI  - Role of Rel/NF-kappaB transcription factors during the outgrowth of the
      vertebrate limb.
AB  - The development of the vertebrate limb serves as an amenable system for studying
      signaling pathways that lead to tissue patterning and proliferation. Limbs
      originate as a consequence of a differential growth of cells from the lateral
      plate mesoderm at specific axial levels. At the tip of the limb primordia the
      progress zone, a proliferating group of mesenchymal cells, induces the overlying
      ectoderm to differentiate into a specialized structure termed the apical
      ectodermal ridge. Subsequent limb outgrowth requires reciprocal signalling
      between the ridge and the progress zone. The Rel/NF-kappaB family of
      transcription factors is induced in response to several signals that lead to cell
      growth, differentiation, inflammatory responses, apoptosis and neoplastic
      transformation. In unstimulated cells, NF-kappaB is associated in the cytoplasm
      with an inhibitory protein, I-kappaB. In response to an external signal, I-kappaB
      is phosphorylated, ubiquitinated and degraded, releasing NF-kappaB to enter the
      nucleus and activate transcription. Here we show that Rel/NF-kappaB genes are
      expressed in the progress zone of the developing chick limb bud. When the
      activity of Rel/NF-kappaB proteins is blocked by infection with viral vectors
      that produce transdominant-negative I-kappaBalpha proteins, limb outgrowth is
      arrested. Our results indicate that Rel/NF-kappaB transcription factors play a
      role in vertebrate limb development.

PMID- 9560159
TI  - Inhibition of NF-kappaB activity results in disruption of the apical ectodermal
      ridge and aberrant limb morphogenesis.
AB  - In Drosophila, the Dorsal protein establishes the embryonic dorso-ventral axis
      during development. Here we show that the vertebrate homologue of Dorsal, nuclear
      factor-kappa B (NF-kappaB), is vital for the formation of the proximo-distal
      organizer of the developing limb bud, the apical ectodermal ridge (AER).
      Transcription of the NF-kappaB proto-oncogene c-rel is regulated, in part, during
      morphogenesis of the limb bud by AER-derived signals such as fibroblast growth
      factors. Interruption of NF-kappaB activity using viral-mediated delivery of an
      inhibitor results in a highly dysmorphic AER, reduction in overall limb size,
      loss of distal elements and reversal in the direction of limb outgrowth.
      Furthermore, inhibition of NF-kappaB activity in limb mesenchyme leads to a
      reduction in expression of Sonic hedgehog and Twist but derepresses expression of
      the bone morphogenetic protein-4 gene. These results are the first evidence that
      vertebrate NF-kappaB proteins act to transmit growth factor signals between the
      ectoderm and the underlying mesenchyme during embryonic limb formation.

PMID- 9560160
TI  - A proteolytic system that compensates for loss of proteasome function.
AB  - Proteolysis is essential for the execution of many cellular functions. These
      include removal of incorrectly folded or damaged proteins, the activation of
      transcription factors, the ordered degradation of proteins involved in cell cycle
      control, and the generation of peptides destined for presentation by class I
      molecules of the major histocompatibility complex. A multisubunit protease
      complex, the proteasome, accomplishes these tasks. Here we show that in mammalian
      cells inactivation of the proteasome by covalent inhibitors allows the outgrowth
      of inhibitor-resistant cells. The growth of such adapted cells is apparently
      maintained by the induction of other proteolytic systems that compensate for the
      loss of proteasomal activity.

PMID- 9560161
TI  - Rap1 mediates sustained MAP kinase activation induced by nerve growth factor.
AB  - Activation of mitogen-activated protein (MAP) kinase (also known as extracellular
      signal-regulated kinase, or ERK) by growth factors can trigger either cell growth
      or differentiation. The intracellular signals that couple growth factors to MAP
      kinase may determine the different effects of growth factors: for example,
      transient activation of MAP kinase by epidermal growth factor stimulates
      proliferation of PC12 cells, whereas they differentiate in response to nerve
      growth factor, which acts partly by inducing a sustained activation of MAP
      kinase. Here we show that activation of MAP kinase by nerve growth factor
      involves two distinct pathways: the initial activation of MAP kinase requires the
      small G protein Ras, but its activation is sustained by the small G protein Rap1.
      Rap1 is activated by CRK adaptor proteins and the guanine-nucleotide-exchange
      factor C3G, and forms a stable complex with B-Raf, an activator of MAP kinase.
      Rap1 is required for at least two indices of neuronal differentiation by nerve
      growth factor: electrical excitability and the induction of neuron-specific
      genes. We propose that the activation of Rap1 by C3G represents a common
      mechanism to induce sustained activation of the MAP kinase cascade in cells that
      express B-Raf.

PMID- 9560162
TI  - The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory
      factor to control Na+/H+ exchange.
AB  - Stimulation of beta2-adrenergic receptors on the cell surface by adrenaline or
      noradrenaline leads to alterations in the metabolism, excitability,
      differentiation and growth of many cell types. These effects have traditionally
      been thought to be mediated exclusively by receptor activation of intracellular G
      proteins. However, certain physiological effects of beta2-adrenergic receptor
      stimulation, notably the regulation of cellular pH by modulation of Na+/H+
      exchanger (NHE) function, do not seem to be entirely dependent on G-protein
      activation. We report here a direct agonist-promoted association of the beta2
      adrenergic receptor with the Na+/H+ exchanger regulatory factor (NHERF), a
      protein that regulates the activity of the Na+/H+ exchanger type 3 (NHE3). NHERF
      binds to the beta2-adrenergic receptor by means of a PDZ-domain-mediated
      interaction with the last few residues of the carboxy-terminal cytoplasmic domain
      of the receptor. Mutation of the final residue of the beta2-adrenergic receptor
      from leucine to alanine abolishes the receptor's interaction with NHERF and also
      markedly alters beta2-adrenergic receptor regulation of NHE3 in cells without
      altering receptor-mediated activation of adenylyl cyclase. Our findings indicate
      that agonist-dependent beta2-adrenergic receptor binding of NHERF plays a role in
      beta2-adrenergic receptor-mediated regulation of Na+/H+ exchange.

PMID- 9560163
TI  - The gender paradox in suicide.
AB  - In most Western countries females have higher rates of suicidal ideation and
      behavior than males, yet mortality from suicide is typically lower for females
      than for males. This article explores the gender paradox of suicidal behavior,
      examines its validity, and critically examines some of the explanations,
      concluding that the gender paradox of suicidal behavior is a real phenomenon and
      not a mere artifact of data collection. At the same time, the gender paradox in
      suicide is a more culture-bound phenomenon than has been traditionally assumed;
      cultural expectations about gender and suicidal behavior strongly determine its
      existence. Evidence from the United States and Canada suggests that the gender
      gap may be more prominent in communities where different suicidal behaviors are
      expected of females and males. These divergent expectations may affect the
      scenarios chosen by females and males, once suicide becomes a possibility, as
      well as the interpretations of those who are charged with determining whether a
      particular behavior is suicidal (e.g., coroners). The realization that cultural
      influences play an important role in the gender paradox of suicidal behaviors
      holds important implications for research and for public policy.

PMID- 9560164
TI  - Gender, culture, and suicidal behavior: a feminist critique of theories and
      research.
AB  - Suicide research has developed historically from philosophical roots in logical
      positivism and structural determinism. Thus, much suicide research has been based
      on assumptions of cause-and-effect relationships, reductionistic analysis, and
      the individual as the primary unit of analysis. In counterpoint, six guiding
      themes define feminist research (Worell & Etaugh, 1994). The present manuscript
      traces these six themes, illustrating them with suicide research projects. By
      challenging scientific tradition, focusing on women, considering power,
      recognizing gender constructs, maintaining awareness of the power of language,
      and promoting active, practical applications, researchers can combine traditional
      and alternative methodologies to make suicide research more robust.

PMID- 9560165
TI  - Gender and the cultural construction of good and bad suicides.
AB  - Some cultures distinguish two or more types of suicide which are evaluated
      differently. The more acceptable or esteemed ones are often not equally
      accessible to everyone within the same society. This article focuses on gender
      differences in the cultural construction of suicide options, and on the exclusion
      of women from superior options. The analysis is based on ethnographic and
      historical data from Native Americans of the Great Plains, Muslim societies in
      Southeast Asia, and tribal societies in the Amazon area of South America.

PMID- 9560166
TI  - Gender and suicide in India: a multiperspective approach.
AB  - The gap between male and female suicide rates in India is relatively small.
      However, society's views on female and male motives are quite different. In order
      to investigate the perceptions of male and female suicide, we interviewed a focus
      group of university professors as well as police inspectors, crime reporters, and
      hospital nurses in Bangalore. We also obtained four narratives of suicide. Women
      tended to be blamed for their own or their husband's suicide, although they were
      also viewed more often as victims of life adversities than men. A historical
      review illustrates that both men and women have been associated with culturally
      sanctioned suicides. One known form is sati, and we discuss the recent case of
      sati-murder of Roop Kanwar in 1987. The social sciences and the media also pay a
      lot of attention to the typical female suicides, symbolizing their role as
      martyrs of society, which seems to compensate for attribution of blame.

PMID- 9560167
TI  - Gender differences in nonfatal suicidal behavior in Pakistan: significance of
      sociocultural factors.
AB  - Suicidal behavior is an understudied subject in Pakistan. A variety of social,
      legal, and religious factors make reporting and data collection on suicide and
      nonfatal suicidal behavior difficult. To study the problem, a retrospective case
      note analysis was carried out in which the sociodemographic and clinical
      characteristics of 262 female and 185 male suicidal individuals admitted to a
      university hospital in Karachi, Pakistan, are compared. Three quarters of the
      suicidal persons were under the age of 30 years. Compared to men, women were
      younger and more often married. Both women and men tended to use self-poisoning
      with benzodiazepines, but more women used organophosphate insecticides. In
      Pakistani society, legal, social, and economic discrimination predisposes women
      to psychological distress and subsequent suicidal behavior. The study highlights
      the need for culture-specific research on suicidal behavior in Pakistan.

PMID- 9560168
TI  - Culture, gender, and suicidal behavior in Sri Lanka.
AB  - In less than 50 years, the rate of suicide among Sri Lankans has risen from a
      modest level to one of the highest in the world. This article describes the
      current pattern of suicides, including sex differences and similarities, and
      reviews some of the institutional practices, material conditions, and social
      norms that may figure in the increases. A study is reported, which asked how
      ordinary Sri Lankans account for suicidal behavior and what practices they
      recommend for assisting suicidal individuals. Gender inflected these accounts,
      with essentialist accounts associated with women's suicides and contextual
      accounts associated with men's suicides.

PMID- 9560169
TI  - Women in cultural transition: suicidal behavior in South African Indian women.
AB  - Young South African Indian women are a population with relatively high rates of
      suicidal behavior. This article presents three illustrative case studies of
      nonfatal suicidal behavior by South African Indian women. The cases are discussed
      in relation to a review of epidemiological, historical, and sociocultural
      perspectives on South African Indian women. It is argued that suicidal behaviors
      in this group can be understood in the context of sociocultural transition.
      Transitional tensions between traditional Indian culture and Westernization have
      an impact on traditional gendered power relations and generate conflicts that
      have intrapsychic and interpersonal consequences for women and for men. These in
      turn may have adverse effects on marital functioning, quality of life, and
      specific aspects of emotional functioning, which have been identified as
      precursors of suicidal behavior. The case studies are discussed with reference to
      gender narratives. Implications for prevention, intervention, and future research
      are discussed.

PMID- 9560171
TI  - Effects of sexual victimization on suicidal ideation and behavior in U.S. college
      women.
AB  - This study examines the relationship between suicidal ideation and behavior and
      five types of sexual victimization in a sample of 393 female undergraduate
      students. Participants completed self-report measures of sexual victimization,
      hopelessness, suicidal ideation, and suicidal behavior. Adult sexual
      victimization, but not childhood sexual abuse, predicted current hopelessness and
      suicidal ideation. Both childhood sexual abuse and adult sexual victimization
      predicted suicidal behavior. One in four rape victims, in contrast to
      approximately 1 in 20 nonvictimized women, had engaged in a suicidal act. Vaginal
      penetration following the threat or use of physical force was a stronger
      predictor of suicidal behavior than penetration without the use of force and/or
      force without penetration. The findings point to the importance of inquiring
      about experiences of sexual victimization when conducting research or treatment
      with suicidal women as well as the need for suicide risk assessment in programs
      for victims of sexual violence.

PMID- 9560170
TI  - Suicidal behavior in a bicultural society: a review of gender and cultural
      differences in adolescents and young persons of Aotearoa/New Zealand.
AB  - During the 1990s, Aotearoa/New Zealand has experienced an alarming increase in
      youth suicide in the Maori and non-Maori populations. Among 23 Organization for
      Economic Cooperation and Development countries surveyed by the World Health
      Organization's (1995) World Health Statistics Annual, New Zealand ranks first for
      fatal suicidal behavior, in males 15-24 years of age, and third for fatal
      suicidal behavior in females. A United Nations Children's Fund (UNICEF, 1996)
      survey of 32 countries places New Zealand males as third highest for fatal
      suicidal behavior, and females as eighth highest in the age group 15-24 years.
      New Zealand has recently undergone a number of social and economic changes that
      have created dramatic social and cultural shifts. Given the rapidity of these
      changes, the shock on such a small country has been difficult to absorb. These
      shifts have placed tremendous pressures on families and service support systems,
      such as health and mental health services, to develop programs that are relevant
      and acceptable for a bicultural society. This article focuses on these changes
      and the effect they have had on cultural narratives of gender and suicidal
      behavior, the different cultural etiologies that underlie these statistics, and
      recommendations for intervention and prevention program development.

PMID- 9560172
TI  - Gender and history of suicidality: are these factors related to U.S. college
      students' current suicidal thoughts, feelings, and actions?
AB  - Gender and history of suicidality (HS vs. NoHS) were related to current symptoms
      of depression, reasons for living, and reports of self-destructive and life
      threatening behavior in a college student sample. Overall, college men reported
      engaging in more life-threatening and potentially suicidal behavior than college
      women on the Life Attitudes Schedule (LAS). No gender effects were obtained on
      the symptoms of depression and reasons for living measures. Results suggest that
      the LAS may be a particularly effective way to identify college students at risk
      for self-destructive and suicidal behavior. As expected, HS individuals were more
      depressed, had fewer reasons for living, and reported engaging in more current
      suicidal and life-threatening behavior than NoHS participants. However, gender
      and history of suicidality were found to interact. NoHS women reported avoiding a
      variety of injury-producing and health-diminishing behaviors that were common for
      all other groups of college students. Meanwhile, HS women endorsed fewer current
      reasons for living than did NoHS women, NoHS men, and NoHS men. These findings
      were interpreted both with regard to cultural and gender-specific expectations
      for the expression of self-destructive, suicidal, and life-threatening behavior.
      Implications for the prevention of college women's and men's suicidal behavior
      were also noted.

PMID- 9560173
TI  - A critical review of pharmacotherapy for youth with anxiety disorders: things are
      not as they seem.
AB  - Given the increasing trend in clinical child psychology and psychiatry toward
      cost-effective and pharmacological treatment, a review of key factors that
      influence treatment outcomes in this area seems warranted. This is especially
      important for the rapidly changing area of childhood anxiety disorders. In this
      article, we look at different change producing procedures to illustrate the claim
      that pharmacological studies are not necessarily what they seem. Specifically,
      pharmacological outcome studies are classified and reviewed on the basis of
      varying "secondary" treatments described in method sections. Three groups and
      efficacy rates were determined: (a) pharmacotherapy only (42.83%), (b)
      pharmacotherapy plus general/supportive psychotherapy (27.74%), and (c)
      pharmacotherapy plus a behavior therapy component (65.28%). We also discuss the
      implications of these findings for research as well as other methodological and
      theoretical concerns regarding the reviewed articles. These concerns include (a)
      methods used to diagnose participants, (b) methods used to assess improvement,
      (c) emphasis on diagnostic categories, (d) exclusionary criteria and comorbidity,
      (e) participant attrition and follow-up, and (f) key developmental and social
      contextual variables.

PMID- 9560174
TI  - Anxiety sensitivity and response to hyperventilation challenge: physiologic
      arousal, interoceptive acuity, and subjective distress.
AB  - Twenty-four female undergraduates, 12 high on anxiety sensitivity and 12 low on
      anxiety sensitivity, were subjected to a hyperventilation challenge task.
      Physiologic and subjective measures of arousal and distress were obtained before,
      during, and after the hyperventilation challenge. Alternating between the eight
      15-second intervals of hyperventilation, participants engaged in a heartbeat
      tracking task for eight 10-second intervals to assess interoceptive acuity.
      Although the hyperventilation challenge produced phase main effects for
      physiologic arousal, and group and time main effects for subjective distress,
      there were no significant interaction effects. Results revealed no significant
      interoceptive acuity differences across the low and high anxiety sensitivity
      groups. However, subjective ratings of physiological sensations during
      hyperventilation were significantly greater for the high anxiety sensitivity
      group. Hierarchical multiple regression analyses revealed that anxiety
      sensitivity accounted for additional variance beyond trait anxiety in explaining
      subjective ratings of arousal and distress in this nonclinical sample in response
      to a hyperventilation challenge.

PMID- 9560175
TI  - The role of self-directed in vivo exposure in combination with cognitive therapy,
      relaxation training, or therapist-assisted exposure in the treatment of panic
      disorder with agoraphobia.
AB  - The effects of self-directed in vivo exposure in the treatment of panic disorder
      with agoraphobia were examined. Seventy-four chronic and severe agoraphobic
      subjects were randomly assigned to Cognitive Therapy plus graded exposure.
      Relaxation Training plus graded exposure, or therapist-assisted graded exposure
      alone. Treatment consisted of 16 weekly 2.5-hour sessions. All subjects received
      programmed practice instructions for engaging in self-directed exposure as a
      concomitant strategy to their primary treatment. All subjects were instructed to
      keep systematic behavioral diary recordings of all self-directed exposure
      practice. The diary data were analyzed across and within treatments and
      assessment phases. Statistically significant findings were obtained across all
      diary measure domains with powerful repeated measures effects observed across all
      treatments. Significant between group effects and treatment x repeated measures
      interactions were obtained across the diary measure domains. Multiple linear
      regressions of in vivo anxiety levels and, to a lesser extent, frequency of self
      directed exposure practice were found to be significantly associated with global
      assessment of severity at posttreatment and 3-month follow-up assessments.
      Furthermore, depression and marital satisfaction were significantly associated
      with in vivo anxiety. These and other findings are discussed with regard to their
      conceptual and clinical implications.

PMID- 9560176
TI  - Problem solving and problem orientation in generalized anxiety disorder.
AB  - The present study's main objective is to examine whether problem orientation and
      problem-solving skills differ according to generalized anxiety disorder (GAD)
      symptom level or clinical status (seeking help for GAD). Its secondary goal is to
      examine whether two cognitive variables (intolerance of uncertainty and beliefs
      about worry) vary according to GAD symptom level or clinical status. Three groups
      of subjects participated in the study: (a) nonclinical moderate worriers (N =
      15), (b) nonclinical subjects meeting GAD criteria by questionnaire (N = 14), and
      (c) GAD patients (N = 14). Problem orientation and problem-solving skills were
      measured with the Social Problem-Solving Inventory (D'Zurilla & Nezu, 1990) and
      the Problem-Solving Inventory (Heppner & Petersen, 1982), whereas the cognitive
      variables were assessed with the Intolerance of Uncertainty questionnaire
      (Freeston, Rheaume, Letarte, Dugas, & Ladouceur, 1994) and the Why Worry?
      questionnaire (Freeston, Rheaume et al., 1994). The results show that problem
      orientation, intolerance of uncertainty, and beliefs about worry were similar in
      subjects meeting GAD criteria by questionnaire and GAD patients, whereas moderate
      worriers had different scores on these variables. Thus, these variables are more
      highly affected by GAD symptom level than by clinical status. The results also
      show that problem-solving skills were unaffected by symptom level and clinical
      status, thereby indicating that knowledge of problem-solving skills is unrelated
      to both GAD symptom level and GAD clinical status. The findings are discussed in
      terms of their theoretical and clinical implications.

PMID- 9560177
TI  - Children's self-talk under conditions of mild anxiety.
AB  - Two studies are described which used think-aloud (Study 1) and verbal thought
      listing (Studies 1 and 2) procedures to assess preadolescent children's self-talk
      under conditions of mild anxiety. The self-talk reported was coded into six
      theoretically meaningful categories and the relationship between self-talk type
      and anxiety (state and trait) examined. Increased levels of anxiety were
      associated with higher rates of negative self-talk, but not clearly associated
      with other types of self-talk. These results suggest negative self-talk plays a
      role in the generation or maintenance of anxiety in normal children. From the
      data, it is unclear to what extent perceived task difficulty contributes to the
      relationship between trait anxiety and negative self-talk. Assessment of self
      regulation (Study 1) identified higher levels of anxiety in children reporting
      awareness of strategies for managing their anxiety.

PMID- 9560178
TI  - Plant parasitic nematodes: digesting a page from the microbe book.

PMID- 9560181
TI  - Line spectral analysis for harmonizable processes.
AB  - Harmonizable processes with spectral mass concentrated on a number of straight
      lines are considered. The asymptotic behavior of the bias and covariance of a
      number of spectral estimates is described. The results generalize those obtained
      for periodic and almost periodic processes.

PMID- 9560180
TI  - Dynamics and function of proteins: the search for general concepts.

PMID- 9560179
TI  - HLA class I specificity for natural killer cell receptor CD94/NKG2A: two for one
      in more ways than one.

PMID- 9560182
TI  - Cosmological implications of a large complete quasar sample.
AB  - Objective and reproducible determinations of the probabilistic significance
      levels of the deviations between theoretical cosmological prediction and direct
      model-independent observation are made for the Large Bright Quasar Sample [Foltz,
      C., Chaffee, F. H., Hewett, P. C., MacAlpine, G. M., Turnshek, D. A., et al.
      (1987) Astron. J. 94, 1423-1460]. The Expanding Universe model as represented by
      the Friedman-Lemaitre cosmology with parameters qo = 0, Lambda = 0 denoted as C1
      and chronometric cosmology (no relevant adjustable parameters) denoted as C2 are
      the cosmologies considered. The mean and the dispersion of the apparent
      magnitudes and the slope of the apparent magnitude-redshift relation are the
      directly observed statistics predicted. The C1 predictions of these cosmology
      independent quantities are deviant by as much as 11sigma from direct observation;
      none of the C2 predictions deviate by >2sigma. The C1 deviations may be
      reconciled with theory by the hypothesis of quasar "evolution," which, however,
      appears incapable of being substantiated through direct observation. The
      excellent quantitative agreement of the C1 deviations with those predicted by C2
      without adjustable parameters for the results of analysis predicated on C1
      indicates that the evolution hypothesis may well be a theoretical artifact.

PMID- 9560183
TI  - Second-order correction to the Bigeleisen-Mayer equation due to the nuclear field
      shift.
AB  - The nuclear field shift affects the electronic, rotational, and vibrational
      energies of polyatomic molecules. The theory of the shifts in molecular spectra
      has been studied by Schlembach and Tiemann [Schlembach, J. & Tiemann, E. (1982)
      Chem. Phys. 68, 21]; measurements of the electronic and rotational shifts of the
      diatomic halides of Pb and Tl have been made by Tiemann et al. [Tiemann, E.,
      Knockel, H. & Schlembach, J. (1982) Ber. Bunsenges. Phys. Chem. 86, 821]. These
      authors have estimated the relative shifts in the harmonic frequencies of these
      compounds due to the nuclear field shift to be of the order of 10(-6). I have
      used this estimate of the relative shift in vibrational frequency to calculate
      the correction to the harmonic oscillator approximation to the isotopic reduced
      partition-function ratio (208)Pb(32)S/(207)Pb(32)S. The correction is 0.3% of the
      harmonic oscillator value at 300 K. In the absence of compelling evidence to the
      contrary, it suffices to calculate the nuclear field effect on the total isotopic
      partition-function ratio from its shift of the electronic zero point energy and
      the unperturbed molecular vibration.

PMID- 9560184
TI  - Chemical requirements for inhibition of gap junction communication by the
      biologically active lipid oleamide.
AB  - Oleamide is an endogenous fatty acid primary amide that possesses sleep-inducing
      properties in animals and has been shown to effect serotonergic systems and block
      gap junction communication in a structurally specific manner. Herein, the
      structural features of oleamide required for inhibition of the gap junction
      mediated chemical and electrical transmission in rat glial cells are defined. The
      effective inhibitors fall into two classes of fatty acid primary amides of which
      oleamide and arachidonamide are the prototypical members. Of these two, oleamide
      constitutes the most effective, and its structural requirements for inhibition of
      the gap junction are well defined. It requires a chain length of 16-24 carbons of
      which 16-18 carbons appears optimal, a polarized terminal carbonyl group capable
      of accepting but not necessarily donating a hydrogen bond, a Delta9 cis double
      bond, and a hydrophobic methyl terminus. Within these constraints, a range of
      modifications are possible, many of which may be expected to improve in vivo
      properties. A select set of agents has been identified that serves both as
      oleamide agonists and as inhibitors of fatty acid amide hydrolase, which is
      responsible for the rapid inactivation of oleamide.

PMID- 9560185
TI  - Engineering analysis of biological variables: an example of blood pressure over 1
      day.
AB  - Almost all variables in biology are nonstationarily stochastic. For these
      variables, the conventional tools leave us a feeling that some valuable
      information is thrown away and that a complex phenomenon is presented
      imprecisely. Here, we apply recent advances initially made in the study of ocean
      waves to study the blood pressure waves in the lung. We note first that, in a
      long wave train, the handling of the local mean is of predominant importance. It
      is shown that a signal can be described by a sum of a series of intrinsic mode
      functions, each of which has zero local mean at all times. The process of
      deriving this series is called the "empirical mode decomposition method."
      Conventionally, Fourier analysis represents the data by sine and cosine
      functions, but no instantaneous frequency can be defined. In the new way, the
      data are represented by intrinsic mode functions, to which Hilbert transform can
      be used. Titchmarsh [Titchmarsh, E. C. (1948) Introduction to the Theory of
      Fourier Integrals (Oxford Univ. Press, Oxford)] has shown that a signal and i
      times its Hilbert transform together define a complex variable. From that complex
      variable, the instantaneous frequency, instantaneous amplitude, Hilbert spectrum,
      and marginal Hilbert spectrum have been defined. In addition, the Gumbel extreme
      value statistics are applied. We present all of these features of the blood
      pressure records here for the reader to see how they look. In the future, we have
      to learn how these features change with disease or interventions.

PMID- 9560186
TI  - The helium paradoxes.
AB  - The ratio 3He/4He (R) plays a central role in models of mantle evolution that
      propose an undegassed lower mantle, rich in the primordial isotope 3He. A large
      primordial volatile-rich reservoir, a feature of recent models, is inconsistent
      with high-temperature accretion and with estimates of crustal and bulk Earth
      chemistry. High R can alternatively reflect high integrated 3He/(U+Th) ratios or
      low 4He abundances, as expected in refractory portions of the upper mantle. I
      show that high R materials are gas-poor and are deficient in radiogenic 4He
      compared with midocean ridge basalts. The seemingly primitive (i.e., high R)
      signatures in "hotspot" magmas may be secondary, derived from CO2-rich gases, or
      residual peridotite, a result of differential partitioning of U and He into
      magmas. A shallow and low 3He source explains the spatial variability and the
      temporal trends of R in ocean islands and is consistent with a volatile-poor
      planet. A shallow origin for the "primitive" He signature in ocean island
      basalts, such as at Loihi, reconciles the paradoxical juxtaposition of crustal,
      seawater, and atmospheric signatures with inferred "primitive" characteristics.
      High 238U/204Pb components in ocean island basalts are generally attributed to
      recycled altered oceanic crust. The low 238U/3He component may be in the
      associated depleted refractory mantle. High 3He/4He ratios are due to low 4He,
      not excess 3He, and do not imply or require a deep or primordial or undegassed
      reservoir. 40Ar in the atmosphere also argues against such models.

PMID- 9560187
TI  - On Calderon's conjecture for the bilinear Hilbert transform.
AB  - We show that the bilinear Hilbert transform defined by maps Lp x Lq into Lr for 1
      < p, q </= infinity, 1/p + 1/q = 1/r, and 2/3 < r < infinity.

PMID- 9560189
TI  - Highly resolved chemical imaging of living cells by using synchrotron infrared
      microspectrometry.
AB  - Using synchrotron radiation as an ultra-bright infrared source, we have been able
      to map the distributions of functional groups such as proteins, lipids, and
      nucleic acids inside a single living cell with a spatial resolution of a few
      microns. In particular, we have mapped the changes in the lipid and protein
      distributions in both the final stages of cell division and also during necrosis.

PMID- 9560188
TI  - Structure of the catalytic domain of avian sarcoma virus integrase with a bound
      HIV-1 integrase-targeted inhibitor.
AB  - The x-ray structures of an inhibitor complex of the catalytic core domain of
      avian sarcoma virus integrase (ASV IN) were solved at 1.9- to 2.0-A resolution at
      two pH values, with and without Mn2+ cations. This inhibitor (Y-3), originally
      identified in a screen for inhibitors of the catalytic activity of HIV type 1
      integrase (HIV-1 IN), was found in the present study to be active against ASV IN
      as well as HIV-1 IN. The Y-3 molecule is located in close proximity to the enzyme
      active site, interacts with the flexible loop, alters loop conformation, and
      affects the conformations of active site residues. As crystallized, a Y-3
      molecule stacks against its symmetry-related mate. Preincubation of IN with metal
      cations does not prevent inhibition, and Y-3 binding does not prevent binding of
      divalent cations to IN. Three compounds chemically related to Y-3 also were
      investigated, but no binding was observed in the crystals. Our results identify
      the structural elements of the inhibitor that likely determine its binding
      properties.

PMID- 9560190
TI  - Regulation of the zinc transporter ZnT-1 by dietary zinc.
AB  - The understanding of mechanisms controlling zinc absorption and metabolism at the
      molecular level has advanced recently. Kinetics of zinc transport have been
      investigated for many years, but only recently have genes coding for proteins
      thought to be involved in the transport process been cloned. Four putative zinc
      transporters, known as ZnT-1 through ZnT-4, have now been described. Among these
      transporters, only ZnT-1 is ubiquitously expressed. In this report, we examine
      the pattern of ZnT-1 expression in the intestine and analyze the regulation of
      ZnT-1 by dietary zinc in both the intestine and liver. Immunofluorescence
      demonstrated that intestinal ZnT-1 was most abundant at the basolateral surface
      of enterocytes lining the villi of the duodenum and jejunum. By Western blot
      analysis, intestinal and liver ZnT-1 protein migrated as a 42- and 36-kDa
      protein, respectively. Dietary zinc supplementation elevated the level of
      intestinal ZnT-1 mRNA and protein approximately 50% and 10%, respectively, but
      had no effect in the liver. In response to an acute oral zinc dose, the level of
      intestinal ZnT-1 mRNA was up-regulated 8-fold, without a corresponding increase
      in ZnT-1 protein. Conversely, the acute oral dose did not affect liver ZnT-1
      mRNA, but resulted in a 5-fold increase in liver ZnT-1 protein. These results
      represent studies on the expression of intestinal and hepatic ZnT-1 in an intact
      animal model. The data suggest that ZnT-1 is at least part of the mechanism by
      which dietary zinc is absorbed and that, despite the zinc responsiveness of the
      ZnT-1 gene, additional factors may be regulating the steady-state level of ZnT-1
      transporter protein.

PMID- 9560191
TI  - Crystal structure of troponin C in complex with troponin I fragment at 2.3-A
      resolution.
AB  - Troponin (Tn), the complex of three subunits (TnC, TnI, and TnT), plays a key
      role in Ca2+-dependent regulation of muscle contraction. To elucidate the
      interactions between the Tn subunits and the conformation of TnC in the Tn
      complex, we have determined the crystal structure of TnC (two Ca2+ bound state)
      in complex with the N-terminal fragment of TnI (TnI1-47). The structure was
      solved by the single isomorphous replacement method in combination with multiple
      wavelength anomalous dispersion data. The refinement converged to a
      crystallographic R factor of 22.2% (Rfree = 32.6%). The central, connecting alpha
      helix observed in the structure of uncomplexed TnC (TnCfree) is unwound at the
      center (residues Ala-87, Lys-88, Gly-89, Lys-90, and Ser-91) and bent by 90
      degrees. As a result, TnC in the complex has a compact globular shape with direct
      interactions between the N- and C-terminal lobes, in contrast to the elongated
      dumb-bell shaped molecule of uncomplexed TnC. The 31-residue long TnI1-47 alpha
      helix stretches on the surface of TnC and stabilizes its compact conformation by
      multiple contacts with both TnC lobes. The amphiphilic C-end of the TnI1-47 alpha
      helix is bound in the hydrophobic pocket of the TnC C-lobe through 38 van der
      Waals interactions. The results indicate the major difference between Ca2+
      receptors integrated with the other proteins (TnC in Tn) and isolated in the
      cytosol (calmodulin). The TnC/TnI1-47 structure implies a mechanism of how Tn
      regulates the muscle contraction and suggests a unique alpha-helical regulatory
      TnI segment, which binds to the N-lobe of TnC in its Ca2+ bound conformation.

PMID- 9560192
TI  - A primitive pathway of porphyrin biosynthesis and enzymology in Desulfovibrio
      vulgaris.
AB  - Culture of Desulfovibrio vulgaris in a medium supplemented with 5-aminolevulinic
      acid and L-methionine-methyl-d3 resulted in the formation of porphyrins
      (sirohydrochlorin, coproporphyrin III, and protoporphyrin IX) in which the methyl
      groups at the C-2 and C-7 positions were deuterated. A previously unknown
      hexacarboxylic acid was also isolated, and its structure was determined to be 12,
      18-didecarboxysirohydrochlorin by mass spectrometry and 1H NMR. These results
      indicate a primitive pathway of heme biosynthesis in D. vulgaris consisting of
      the following enzymatic steps: (i) methylation of the C-2 and C-7 positions of
      uroporphyrinogen III to form precorrin-2 (dihydrosirohydrochlorin); (ii)
      decarboxylation of acetate groups at the C-12 and C-18 positions of precorrin-2
      to form 12,18-didecarboxyprecorrin-2; (iii) elimination of acetate groups of the
      C-2 and C-7 positions of 12,18-didecarboxyprecorrin-2 to form coproporphyrinogen
      III; and (iv) conversion of coproporphyrinogen III to protoporphyrin IX via
      protoporphyrinogen IX. We isolated the following three enzymatic activities
      involved in steps i-iii from the soluble fraction of the cells by anion-exchange
      chromatography: S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase,
      precorrin-2 12,18-acetate decarboxylase, and 12, 18-didecarboxyprecorrin-2 2,7
      decarboxymethylase; all enzymic products were converted into autooxidized methyl
      esters and analyzed by thin-layer chromatography, UV-visible (UV-VIS) absorption,
      and mass spectrometry. The enzymatic reactions in D. vulgaris shed new light on
      porphyrin biosynthesis at an early stage in the evolution of prokaryotes.

PMID- 9560193
TI  - Leukotriene D4 and cystinyl-bis-glycine metabolism in membrane-bound dipeptidase
      deficient mice.
AB  - We have developed mice deficient in membrane-bound dipeptidase (MBD, EC
      3.4.13.19), the enzyme believed to be responsible for the conversion of
      leukotriene D4 (LTD4) to leukotriene E4 (LTE4). The MBD mutation generated by us
      was demonstrated to be a null mutation by Northern blot analysis and the absence
      of beta-lactamase activity in lung, kidney, small intestine, and heart. MBD gene
      deletion had no effect on viability or fertility. The mutant mice retain partial
      ability to convert LTD4 to LTE4, ranging from 80-90% of the wild-type values in
      small intestine and liver to 16% in kidney and 40% in lung, heart, and pancreas.
      MBD is also believed to function consecutively after gamma-glutamyl
      transpeptidase to cleave cystinyl-bis-glycine (cys-bis-gly) generated from
      glutathione cleavage. Our data indicate that kidney homogenates from MBD
      deficient mice retain approximately 40% of their ability to cleave cys-bis-gly,
      consistent with only modest elevations (3-5-fold) of cys-bis-gly in urine from
      MBD-deficient mice. These observations demonstrate that the conversion of LTD4 to
      LTE4 and the degradation of cys-bis-gly are catalyzed by at least two alternative
      pathways (one of which is MBD) that complement each other to varying extents in
      different tissues.

PMID- 9560194
TI  - Regulation of a nuclear export signal by an adjacent inhibitory sequence: the
      effector domain of the influenza virus NS1 protein.
AB  - In the cell nucleus the NS1 protein of influenza A virus inhibits both pre-mRNA
      splicing and the nuclear export of mRNAs. Both the RNA-binding and effector
      domains of the protein are required for these nuclear functions. Here we
      demonstrate that the NS1 protein has a latent nuclear export signal (NES) that is
      located at the amino end of the effector domain. In uninfected, transfected cells
      the NS1 protein is localized in the nucleus because the NES is specifically
      inhibited by the adjacent amino acid sequence in the effector domain.
      Substitution of alanine residues for specific amino acids in the adjacent
      sequence abrogates its inhibitory activity, thereby unmasking the NES and causing
      the full-length NS1 protein to be localized to the cytoplasm. In contrast to
      uninfected cells, a substantial amount of the NS1 protein in influenza virus
      infected cells is located in the cytoplasm. Consequently, the NES of these NS1
      protein molecules is unmasked in infected cells, indicating that the NS1 protein
      most likely carries out functions in the cytoplasm as well as the nucleus. A
      dramatically different localization of the NS1 protein occurs in cells that are
      infected by a virus encoding an NS1 protein lacking the NES: the shortened NS1
      protein molecules are almost totally in the nucleus. Because the NES of the full
      length NS1 protein is unmasked in infected but not uninfected cells, it is likely
      that this unmasking results from a specific interaction of another virus-specific
      protein with the NS1 protein.

PMID- 9560195
TI  - Experimental support for a beta-propeller domain in integrin alpha-subunits and a
      calcium binding site on its lower surface.
AB  - Integrins are large, heterodimeric surface molecules of wide importance in cell
      adhesion. The N-terminal half of all integrin alpha-subunits contains seven weak
      sequence repeats of approximately 60 amino acids that are important in ligand
      binding and have been predicted to fold cooperatively into a single beta
      propeller domain with seven beta-sheets. We provide evidence supporting this
      model with a mouse mAb to human Mac-1 (alphaM beta2, CD11b/CD18). This antibody,
      CBRM1/20, binds to amino acid residues that are in different repeats and are 94
      residues apart in the primary structure in the loop between strands 1 and 2 of
      beta-sheet 5 and in the loop between strands 3 and 4 of beta-sheet 6. The 1-2
      loops of beta-sheets 5-7 in integrins have EF hand-like Ca2+-binding motifs.
      CBRM1/20 binds to Mac-1 in the presence of Ca2+ or Sr2+ with an EC50 of 0.2 mM.
      Mg2+ or Mn2+ cannot substitute. Antibodies to other epitopes on the Mac-1 beta
      propeller domain bind in the absence of calcium. mAb CBRM1/20 does not block
      ligand binding. Thus, the region on the lower surface of the beta-propeller
      domain to which mAb CBRM1/20 binds does not bind ligand and, furthermore, cannot
      bind other integrin domains, such as those of the beta-subunit.

PMID- 9560196
TI  - Crystal structures of two tropinone reductases: different reaction
      stereospecificities in the same protein fold.
AB  - A pair of tropinone reductases (TRs) share 64% of the same amino acid residues
      and belong to the short-chain dehydrogenase/reductase family. In the synthesis of
      tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of
      an alkaloid intermediate, tropinone, to hydroxy groups with different
      diastereomeric configurations. To clarify the structural basis for their
      different reaction stereospecificities, we determined the crystal structures of
      the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two
      enzymes was almost identical. The conservation was not confined within the core
      domains that are conserved within the protein family but extended outside the
      core domain where each family member has its characteristic structure. The
      binding sites for the cofactor and the positions of the active site residues were
      well conserved between the two TRs. The substrate binding site was composed
      mostly of hydrophobic amino acids in both TRs, but the presence of different
      charged residues conferred different electrostatic environments on the two
      enzymes. A modeling study indicated that these charged residues play a major role
      in controlling the binding orientation of tropinone within the substrate binding
      site, thereby determining the stereospecificity of the reaction product. The
      results obtained herein raise the possibility that in certain cases different
      stereospecificities can be acquired in enzymes by changing a few amino acid
      residues within substrate binding sites.

PMID- 9560197
TI  - Protein-bound acrolein: potential markers for oxidative stress.
AB  - Acrolein (CH2==CH---CHO) is known as a ubiquitous pollutant in the environment.
      Here we show that this notorious aldehyde is not just a pollutant, but also a
      lipid peroxidation product that could be ubiquitously generated in biological
      systems. Upon incubation with BSA, acrolein was rapidly incorporated into the
      protein and generated the protein-linked carbonyl derivative, a putative marker
      of oxidatively modified proteins under oxidative stress. To verify the presence
      of protein-bound acrolein in vivo, the mAb (mAb5F6) against the acrolein-modified
      keyhole limpet hemocyanin was raised. It was found that the acrolein-lysine
      adduct, Nepsilon-(3-formyl-3, 4-dehydropiperidino)lysine, constitutes an epitope
      of the antibody. Immunohistochemical analysis of atherosclerotic lesions from a
      human aorta demonstrated that antigenic materials recognized by mAb5F6 indeed
      constituted the lesions, in which intense positivity was associated primarily
      with macrophage-derived foam cells and the thickening neointima of arterial
      walls. The observations that (i) oxidative modification of low-density
      lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts and
      (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein
      resulted in the formation of antigenic materials suggested that polyunsaturated
      fatty acids are sources of acrolein that cause the production of protein-bound
      acrolein. These data suggest that the protein-bound acrolein represents potential
      markers of oxidative stress and long-term damage to protein in aging,
      atherosclerosis, and diabetes.

PMID- 9560198
TI  - Mechanism of platelet inhibition by nitric oxide: in vivo phosphorylation of
      thromboxane receptor by cyclic GMP-dependent protein kinase.
AB  - Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet activation.
      NO stimulates production of cGMP and activates cGMP-dependent protein kinase (G
      kinase), which by an unknown mechanism leads to inhibition of Galphaq
      phospholipase C-inositol 1, 4,5-triphosphate signaling and intracellular calcium
      mobilization for several important agonists, including thromboxane A2 (TXA2). To
      explore the mechanism of platelet inhibition by NO, activation of platelet TXA2
      receptors in the presence of cGMP was studied. The nonhydrolyzable analog 8-bromo
      cyclic GMP (8-Br-cGMP) potently inhibited activation of the TXA2-specific GTPase
      in platelet membranes in a concentration-dependent fashion, suggesting that G
      kinase catalyzes the phosphorylation of some proximal component of the receptor-G
      protein signaling pathway. Nanomolar concentrations of G kinase were found to
      catalyze the phosphorylation of platelet TXA2 receptors in vitro, but not Galphaq
      copurifying with the TXA2 receptors in these experiments. Using immunoaffinity
      methods, in vivo phosphorylation of TXA2 receptors by cyclic GMP was demonstrated
      from 32P-labeled cells treated with 8-Br-cGMP. Peptide mapping studies of in vivo
      phosphorylated TXA2 receptors demonstrated cGMP mediates phosphorylation of the
      carboxyl terminus of the TXA2 receptor. G kinase also catalyzed the
      phosphorylation of peptides corresponding to the cytoplasmic tails of both alpha
      and beta forms of the receptor but not control peptide or a peptide corresponding
      to the third intracytoplasmic loop of the TXA2 receptor. These data identify TXA2
      receptors as cGMP-dependent protein kinase substrates and support a novel
      mechanism for the inhibition of cell function by NO in which activation of G
      kinase inhibits signaling by G protein-coupled receptors by catalyzing their
      phosphorylation.

PMID- 9560199
TI  - Epstein-Barr virus growth-transformed cells are converted to malignancy following
      transfection of a 1.3-kb CATR1 antisense construct independent of a change in the
      level of c-myc expression followed by a 8;14 chromosomal translocation.
AB  - The AGLCL Epstein-Barr virus (EBV) growth-transformed cell line is incapable of
      inducing tumors in nude mice. When the cells were transfected with a 1.3-kb CATR1
      antisense cDNA construct, progressively growing lymphomas could be induced in
      nude mice. Chromosome analysis of the parental, transfected, and tumor cells
      revealed that a chromosomal translocation t(8;14)(q24.1;q32) had occurred in the
      transfected cells and was retained in cells derived from tumors. Moreover,
      enhanced c-myc expression, usually associated with this translocation, was either
      unchanged or under-expressed. These data suggest that the malignant
      transformation of the EBV growth-transformed cells was independent of c-myc
      expression and suggest that the CATR1 gene may act synergistically with the
      chromosomal translocation facilitating the conversion of AGLCL cells from a
      growth-transformed state to a malignant phenotype.

PMID- 9560201
TI  - Endogenous cellulases in animals: isolation of beta-1, 4-endoglucanase genes from
      two species of plant-parasitic cyst nematodes.
AB  - beta-1,4-Endoglucanases (EGases, EC 3.2.1.4) degrade polysaccharides possessing
      beta-1,4-glucan backbones such as cellulose and xyloglucan and have been found
      among extremely variegated taxonomic groups. Although many animal species depend
      on cellulose as their main energy source, most omnivores and herbivores are
      unable to produce EGases endogenously. So far, all previously identified EGase
      genes involved in the digestive system of animals originate from symbiotic
      microorganisms. Here we report on the synthesis of EGases in the esophageal
      glands of the cyst nematodes Globodera rostochiensis and Heterodera glycines.
      From each of the nematode species, two cDNAs were characterized and hydrophobic
      cluster analysis revealed that the four catalytic domains belong to family 5 of
      the glycosyl hydrolases (EC 3.2.1, 3.2.2, and 3.2.3). These domains show 37-44%
      overall amino acid identity with EGases from the bacteria Erwinia chrysanthemi,
      Clostridium acetobutylicum, and Bacillus subtilis. One EGase with a bacterial
      type of cellulose-binding domain was identified for each nematode species. The
      leucine-rich hydrophobic core of the signal peptide and the presence of a
      polyadenylated 3' end precluded the EGases from being of bacterial origin. Cyst
      nematodes are obligatory plant parasites and the identified EGases presumably
      facilitate the intracellular migration through plant roots by partial cell wall
      degradation.

PMID- 9560200
TI  - Escherichia coli rho factor induces release of yeast RNA polymerase II but not
      polymerase I or III.
AB  - Purified RNA polymerase II (pol II) from the yeast Saccharomyces cerevisiae
      pauses without releasing at many locations during in vitro transcription. Pausing
      can be induced by intrinsic DNA sequence as well as by specific DNA bound
      proteins such as the RNA pol I termination factor, Reb1p, or lac repressor.
      Addition of rho termination factor from E. coli induces RNA pol II to release at
      all of these pause sites. Rho-induced release of pol II requires both a rho
      binding site in the transcript upstream of the pause sites as well as hydrolysis
      of ATP. In contrast, rho factor has no effect on either pausing or release by RNA
      pol I or III. When combined with previous observations, these results suggest
      that RNA pol II may terminate by a mechanism closely related to the rho-dependent
      mechanism of prokaryotes. In contrast, pol I and III appear to utilize a
      mechanism more related to the rho-independent terminators of prokaryotes.

PMID- 9560202
TI  - The Rhizobium meliloti ExoK and ExsH glycanases specifically depolymerize nascent
      succinoglycan chains.
AB  - The Rhizobium meliloti ExoK and ExsH glycanases have been proposed to contribute
      to production of low molecular weight (LMW) succinoglycan by depolymerizing high
      molecular weight succinoglycan chains in R. meliloti cultures. We expressed and
      purified ExoK and ExsH and determined that neither enzyme can extensively cleave
      succinoglycan prepared from R. meliloti cultures, although neutral/heat treatment
      and acid/heat treatment convert succinoglycan to forms that can be cleaved
      efficiently by both enzymes. These results were somewhat surprising, given that
      the exoK+ and exsH+ genes play a crucial role in production of LMW succinoglycan
      in R. meliloti cultures. We demonstrated by Western blot analyses that R.
      meliloti expresses ExoK and ExsH, that both proteins can be detected
      extracellularly, and that ExsH secretion depends on the prsD+/prsE+ genes,
      consistent with previous predictions based on mutant analyses. Furthermore, we
      determined that the depolymerization activities associated with purified ExoK and
      ExsH are comparable with exoK+ and exsH+-dependent depolymerization activities
      expressed in R. meliloti cultures. We resolved the apparent contradiction between
      the results of our previous genetic analyses and depolymerization assays by
      determining that ExoK and ExsH can cleave high molecular weight succinoglycan
      that is being produced actively by R. meliloti, but not succinoglycan that has
      accumulated in cultures, to yield LMW succinoglycan. We propose that ExoK and
      ExsH dynamically regulate the molecular weight distribution of succinoglycan by
      cleaving nascent succinoglycan only during a limited period after its synthesis,
      perhaps before it undergoes a time-dependent change in its conformation or
      aggregation state.

PMID- 9560203
TI  - Acetylation at Lys-92 enhances signaling by the chemotaxis response regulator
      protein CheY.
AB  - When Escherichia coli cells lacking all chemotaxis proteins except the response
      regulator CheY are exposed to acetate, clockwise flagellar rotation results,
      indicating the acetate stimulus has activated signaling by CheY. Acetate can be
      converted to acetyl-CoA by either of two different metabolic pathways, which
      proceed through acetyl phosphate or acetyl-AMP intermediates. In turn, CheY can
      be covalently modified by either intermediate in vitro, leading to
      phosphorylation or acetylation, respectively. Either pathway is sufficient to
      support the CheY-mediated response to acetate in vivo. Whereas phosphorylation of
      Asp-57 is a recognized mechanism for activation of CheY to stimulate clockwise
      flagellar rotation, acetylation of CheY is less well characterized. We found
      evidence for multiple CheY acetylation sites by mass spectrometry and directly
      identified Lys-92 and Lys-109 as acetylation sites by Edman degradation of
      peptides from [14C]acetate-labeled CheY. Replacement of CheY Lys-92, the
      preferred acetylation site, with Arg has little effect on chemotaxis but
      completely prevents the response to acetate via the acetyl-AMP pathway. Thus
      acetylation of Lys-92 activates clockwise signaling by CheY in vivo. The
      mechanism by which acetylation activates CheY apparently is not simple charge
      neutralization, nor does it involve enhanced binding to the FliM flagellar switch
      protein. Thus acetylation probably affects signal generation by CheY at a step
      after switch binding.

PMID- 9560204
TI  - Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory
      protein 2: implications for degradation of oxidized proteins.
AB  - The ability of iron to catalyze formation of reactive oxygen species
      significantly contributes to its toxicity in cells and animals. Iron uptake and
      distribution is regulated tightly in mammalian cells, in part by iron regulatory
      protein 2 (IRP2), a protein that is degraded efficiently by the proteasome in
      iron-replete cells. Here, we demonstrate that IRP2 is oxidized and ubiquitinated
      in cells before degradation. Moreover, iron-dependent oxidation converts IRP2
      into a substrate for ubiquitination in vitro. A regulatory pathway is described
      in which excess iron is sensed by its ability to catalyze site-specific
      oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated IRP2
      subsequently is degraded by the proteasome. Selective targeting and removal of
      oxidatively modified proteins may contribute to the turnover of many proteins
      that are degraded by the proteasome.

PMID- 9560205
TI  - Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear
      RNAs.
AB  - In several forms of beta-thalassemia, mutations in the second intron of the beta
      globin gene create aberrant 5' splice sites and activate a common cryptic 3'
      splice site upstream. As a result, the thalassemic beta-globin pre-mRNAs are
      spliced almost exclusively via the aberrant splice sites leading to a deficiency
      of correctly spliced beta-globin mRNA and, consequently, beta-globin. We have
      designed a series of vectors that express modified U7 snRNAs containing sequences
      antisense to either the aberrant 5' or 3' splice sites in the IVS2-705
      thalassemic pre-mRNA. Transient expression of modified U7 snRNAs in a HeLa cell
      line stably expressing the IVS2-705 beta-globin gene restored up to 65% of
      correct splicing in a sequence-specific and dose-dependent manner. Cell lines
      that stably coexpressed IVS2-705 pre-mRNA and appropriately modified U7 snRNA
      exhibited up to 55% of permanent restoration of correct splicing and expression
      of full-length beta-globin protein. This novel approach provides a potential
      alternative to gene replacement therapies.

PMID- 9560206
TI  - Specificity in cholesterol regulation of gene expression by coevolution of sterol
      regulatory DNA element and its binding protein.
AB  - When demand for cholesterol rises in mammalian cells, the sterol regulatory
      element (SRE) binding proteins (SREBPs) are released from their membrane anchor
      through proteolysis. Then, the N-terminal region enters the nucleus and activates
      genes of cholesterol uptake and biosynthesis. Basic helix-loop-helix (bHLH)
      proteins such as SREBPs bind to a palindromic DNA sequence called the E-box (5'
      CANNTG-3'). However, SREBPs are special because they also bind direct repeat
      elements called SREs. Importantly, sterol regulation of all promoters studied
      thus far is mediated by SREBP binding only to SREs. To study the reason for this
      we converted the direct repeat SRE from the sterol-regulated low-density
      lipoprotein receptor promoter into an E-box. In this report we show that SREBPs
      are still able to bind and activate this promoter however, sterol regulation is
      lost. The results are consistent with the mutant promoter being a target for
      promiscuous activation by constitutively expressed E-box binding bHLH proteins
      that are not regulated by cholesterol. Kim and coworkers [Kim, J. B., Spotts, G.
      D., Halvorsen, Y.-D., Shih, H.-M., Ellenberger, T., Towle, H. C. & Spiegelman, B.
      M. (1995) Mol. Cell. Biol. 15, 2582-2588] demonstrated that the dual DNA binding
      specificity of SREBPs is caused by a specific tyrosine in the conserved basic
      region of the DNA binding domain that corresponds to an arginine in all other
      bHLH proteins that recognize only E-boxes. Taken together the data suggest an
      evolutionary mechanism where a DNA binding protein along with its recognition
      site have coevolved to ensure maximal specificity and sensitivity in a crucial
      nutritional regulatory response.

PMID- 9560207
TI  - Mapping of the ligand-selective domain of the Xenopus laevis corticotropin
      releasing factor receptor 1: implications for the ligand-binding site.
AB  - The nonselective human corticotropin-releasing factor receptor 1 (hCRF-R1) and
      the ligand-selective Xenopus CRF-R1 (xCRF-R1) were compared. To understand the
      interactions of sauvagine and ovine CRF, both high-affinity ligands for hCRF-R1
      but surprisingly weak ligands for xCRF-R1, chimeric receptors of hCRF-R1 and xCRF
      R1 followed by double or multiple point mutations were constructed. Binding
      studies and cAMP assays demonstrated that the N-terminal domain exhibited the
      complete ligand selectivity of xCRF-R1. The important region was mapped between
      amino acids 70 and 89; replacement of amino acids Arg76, Asn81, Gly83, Leu88, and
      Ala89 in hCRF-R1 with the corresponding amino acids of xCRF-R1 (Gln76, Gly81,
      Val83, His88, and Leu89) resulted in a receptor that had approximately 30-fold
      higher affinity for human/rat CRF than for sauvagine. Mutagenesis of these amino
      acids in xCRF-R1 to the human sequence completely abolished the ligand
      selectivity of xCRF-R1. Mutagenesis of amino acids 88 and 89 in hCRF-R1 or xCRF
      R1 had only a minor (approximately 2.5-fold) effect on the ligand selectivity of
      the mutant receptor. Substitution of Arg76, Asn81, and Gly83 in hCRF-R1 with the
      corresponding sequence of xCRF-R1 (Gln76, Gly81, and Val83) resulted in a
      receptor with approximately 11-fold higher affinity for human/rat CRF compared
      with ovine CRF or sauvagine. When only two of these three amino acids were
      mutated, no effect on the ligand selectivity was observed. On the basis of these
      data, it is suggested that amino acids 70-89 of CRF-R1 are important for the
      ligand binding site.

PMID- 9560208
TI  - Perturbation of nucleosome core structure by the SWI/SNF complex persists after
      its detachment, enhancing subsequent transcription factor binding.
AB  - To investigate the mechanism of SWI/SNF action, we have analyzed the pathway by
      which SWI/SNF stimulates formation of transcription factor-bound nucleosome core
      complexes. We report here that the SWI/SNF complex binds directly to nucleosome
      cores and uses the energy of ATP hydrolysis to disrupt histone/DNA interactions,
      altering the preferred path of DNA bending around the histone octamer. This
      disruption occurs without dissociating the DNA from the surface of the histone
      octamer. ATP-dependent disruption of nucleosomal DNA by SWI/SNF generates an
      altered nucleosome core conformation that can persist for an extended period
      after detachment of the SWI/SNF complex. This disrupted conformation retains an
      enhanced affinity for the transcription factor GAL4-AH. Thus, ATP-dependent
      nucleosome core disruption and enhanced binding of the transcription factor can
      be temporally separated. These results indicate that SWI/SNF can act transiently
      in the remodeling of chromatin structure, even before interactions of
      transcription factors.

PMID- 9560210
TI  - Evidence that HetR protein is an unusual serine-type protease.
AB  - The hetR gene plays a very important role in cell differentiation of
      heterocystous cyanobacteria. To understand the mechanism of the hetR gene product
      in regulation of heterocyst differentiation, the recombinant HetR protein (rHetR)
      was overproduced in Escherichia coli. Purified rHetR was unstable and degraded
      easily in solution. Phenylmethanesulfonyl fluoride, a serine-type protease
      inhibitor, prevented the degradation and was shown to modify covalently rHetR.
      Dansyl fluoride (DnsF), another serine-type protease inhibitor, also covalently
      modifies rHetR as shown by electrophoresis and electroblotting of the labeled
      rHetR and by MS. The labeling of rHetR with phenylmethanesulfonyl fluoride and
      DnsF was at the same site of rHetR and required Ca2+. S179N-rHetR, a mutant
      protein from strain 216 of Anabaena PCC 7120, which cannot differentiate
      heterocysts because of the mutation, was also overproduced and characterized.
      Although S170N-rHetR still can be labeled with DnsF, no proteolysis was observed,
      suggesting that Ser179 is involved in proteolytic activity. DnsF-labeled rHetR
      was digested with trypsin, and the labeled peptide was isolated and sequenced.
      The labeled peptide matches a sequence from HetR. These results show that HetR is
      a protease.

PMID- 9560209
TI  - A stationary phase protein in Escherichia coli with binding activity to the major
      sigma subunit of RNA polymerase.
AB  - Switching of the transcription pattern in Escherichia coli during the growth
      transition from exponential to stationary phase is accompanied by the replacement
      of the RNA polymerase-associated sigma70 subunit (sigmaD) with sigma38 (sigmaS).
      A fraction of the sigma70 subunit in stationary phase cell extracts was found to
      exist as a complex with a novel protein, designated Rsd (Regulator of sigma D).
      The intracellular level of Rsd starts to increase during the transition from
      growing to stationary phase. The rsd gene was identified at 90 min on the E. coli
      chromosome. Overexpressed and purified Rsd protein formed complexes in vitro with
      sigma70 but not with other sigma subunits, sigmaN, sigmaS, sigmaH, sigmaF, and
      sigmaE. Analysis of proteolytic fragments of sigma70 indicated that Rsd binds at
      or downstream of region 4, the promoter -35 recognition domain. The isolated Rsd
      inhibited transcription in vitro to various extents depending on the promoters
      used. We propose that Rsd is a stationary phase E. coli protein with regulatory
      activity of the sigma70 function.

PMID- 9560211
TI  - Phospholipid composition of the mammalian red cell membrane can be rationalized
      by a superlattice model.
AB  - Although the phospholipid composition of the erythrocyte membrane has been
      studied extensively, it remains an enigma as to how the observed composition
      arises and is maintained. We show here that the phospholipid composition of the
      human erythrocyte membrane as a whole, as well as the composition of its
      individual leaflets, is closely predicted by a model proposing that phospholipid
      head groups tend to adopt regular, superlattice-like lateral distributions. The
      phospholipid composition of the erythrocyte membrane from most other mammalian
      species, as well as of the platelet plasma membrane, also agrees closely with the
      predictions of the superlattice model. Statistical analyses indicate that the
      agreement between the observed and predicted compositions is highly significant,
      thus suggesting that head group superlattices may indeed play a central role in
      the maintenance of the phospholipid composition of the erythrocyte membrane.

PMID- 9560213
TI  - How evolution makes proteins fold quickly.
AB  - Sequences of fast-folding model proteins (48 residues long on a cubic lattice)
      were generated by an evolution-like selection toward fast folding. We find that
      fast-folding proteins exhibit a specific folding mechanism in which all
      transition state conformations share a smaller subset of common contacts (folding
      nucleus). Acceleration of folding was accompanied by dramatic strengthening of
      interactions in the folding nucleus whereas average energy of nonnucleus
      interactions remained largely unchanged. Furthermore, the residues involved in
      the nucleus are the most conserved ones within families of evolved sequences. Our
      results imply that for each protein structure there is a small number of
      conserved positions that are key determinants of fast folding into that
      structure. This conjecture was tested on two protein superfamilies: the first
      having the classical monophosphate binding fold (CMBF; 98 families) and the
      second having type-III repeat fold (47 families). For each superfamily, we
      discovered a few positions that exhibit very strong and statistically significant
      "conservatism of conservatism"-amino acids in those positions are conserved
      within every family whereas the actual types of amino acids varied from family to
      family. Those amino acids are in spatial contact with each other. The
      experimental data of Serrano and coworkers [Lopez-Hernandez, E. & Serrano, L.
      (1996) Fold. Des. (London) 1, 43-55]. for one of the proteins of the CMBF
      superfamily (CheY) show that residues identified this way indeed belong to the
      folding nucleus. Further analysis revealed deep connections between nucleation in
      CMBF proteins and their function.

PMID- 9560212
TI  - Dynamics of different functional parts of bacteriorhodopsin: H-2H labeling and
      neutron scattering.
AB  - We show that dynamics of specific amino acids within a protein can be
      characterized by neutron spectroscopy and hydrogen-deuterium labeling, and we
      present data on the motions of a selected set of groups within bacteriorhodopsin
      (BR), the retinal-based proton pump in the purple membrane of halophilic Archaea.
      Elastic incoherent neutron scattering experiments allow the definition of motions
      in the nano- to picosecond time scale and have revealed a dynamical transition
      from a harmonic to a softer, anharmonic atomic fluctuation regime in the global
      behavior of proteins. Biological activity in proteins is correlated with this
      transition, suggesting that flexibility is required for function. Elastic
      incoherent neutron scattering is dominated by H atom scattering, and to study the
      dynamics of a selected part of BR, fully deuterated purple membrane with BR
      containing H-retinal, H-tryptophan, and H-methionine was prepared
      biosynthetically in Halobacterium salinarum. These amino acids cluster in the
      functional center of the protein. In contrast to the protein globally, the
      thermal motions of the labeled atoms were found to be shielded from solvent
      melting effects at 260 K. Above this temperature, the labeled groups appear as
      more rigid than the rest of the protein, with a significantly smaller mean square
      amplitude of motion. These experimental results quantify the dynamical
      heterogeneity of BR (which meets the functional requirements of global
      flexibility), on the one hand, to allow large conformational changes in the
      molecule and of a more rigid region in the protein, on the other, to control
      stereo-specific selection of retinal conformations.

PMID- 9560214
TI  - The sequences of small proteins are not extensively optimized for rapid folding
      by natural selection.
AB  - The thermodynamic stabilities of small protein domains are clearly subject to
      natural selection, but it is less clear whether the rapid folding rates typically
      observed for such proteins are consequences of direct evolutionary optimization
      or reflect intrinsic physical properties of the polypeptide chain. This issue can
      be investigated by comparing the folding rates of laboratory-generated protein
      sequences to those of naturally occurring sequences provided that the method by
      which the sequences are generated has no kinetic bias. Herein we report the
      folding thermodynamics and kinetics of 12 heavily mutated variants of the small
      IgG binding domain of protein L retrieved from high-complexity combinatorial
      libraries by using a phage-display selection for proper folding that does not
      discriminate between rapidly and slowly folding proteins. Although the
      stabilities of all variants were decreased, many of the variants fold faster than
      wild type. Taken together with similar results for the src homology 3 domain,
      this observation suggests that the sequences of small proteins have not been
      extensively optimized for rapid folding; instead, rapid folding appears to be a
      consequence of selection for stability.

PMID- 9560215
TI  - Are protein folds atypical?
AB  - Protein structures are a very special class among all possible structures. It has
      been suggested that a "designability principle" plays a crucial role in nature's
      selection of protein sequences and structures. Here, we provide a theoretical
      base for such a selection principle, using a simple model of protein folding
      based on hydrophobic interactions. A structure is reduced to a string of 0s and
      1s, which represent the surface and core sites, respectively, as the backbone is
      traced. Each structure is therefore associated with one point in a high
      dimensional space. Sequences are represented by strings of their hydrophobicities
      and thus can be mapped into the same space. A sequence that lies closer to a
      particular structure in this space than to any other structures will have that
      structure as its ground state. Atypical structures, namely those far away from
      other structures in the high dimensional space, have more sequences that fold
      into them and are thermodynamically more stable. We argue that the most common
      folds of proteins are the most atypical in the space of possible structures.

PMID- 9560216
TI  - Localization of nascent RNA and CREB binding protein with the PML-containing
      nuclear body.
AB  - The cellular role of the PML-containing nuclear bodies also known as ND10 or PODs
      remains elusive despite links to oncogenesis and viral replication. Although a
      potential role in transcription has been considered, direct evidence has been
      lacking. By developing a novel in vivo nucleic acid labeling approach, we
      demonstrate the existence of nascent RNA polymerase II transcripts within this
      nuclear body. In addition, PML and the transactivation cofactor, CREB binding
      protein (CBP), colocalize within the nucleus. Furthermore, we show that CBP in
      contrast to PML is distributed throughout the internal core of the structure.
      Collectively, these findings support a role for this nuclear body in
      transcriptional regulation.

PMID- 9560217
TI  - Bax directly induces release of cytochrome c from isolated mitochondria.
AB  - Bax is a pro-apoptotic member of the Bcl-2 protein family that resides in the
      outer mitochondrial membrane. It is controversial whether Bax promotes cell death
      directly through its putative function as a channel protein versus indirectly by
      inhibiting cellular regulators of the cell death proteases (caspases). We show
      here that addition of submicromolar amounts of recombinant Bax protein to
      isolated mitochondria can induce cytochrome c (Cyt c) release, whereas a peptide
      representing the Bax BH3 domain was inactive. When placed into purified cytosol,
      neither mitochondria nor Bax individually induced proteolytic processing and
      activation of caspases. In contrast, the combination of Bax and mitochondria
      triggered release of Cyt c from mitochondria and induced caspase activation in
      cytosols. Supernatants from Bax-treated mitochondria also induced caspase
      processing and activation. Recombinant Bcl-XL protein abrogated Bax-induced
      release of Cyt c from isolated mitochondria and prevented caspase activation. In
      contrast, the broad-specificity caspase inhibitor benzyloxycarbonyl-valinyl
      alaninyl-aspartyl-(0-methyl)- fluoromethylketone (zVAD-fmk) and the caspase
      inhibiting protein X-IAP had no effect on Bax-induced release of Cyt c from
      mitochondria in vitro but prevented the subsequent activation of caspases in
      cytosolic extracts. Unlike Ca2+, a classical inducer of mitochondrial
      permeability transition, Bax did not induce swelling of mitochondria in vitro.
      Because the organellar swelling caused by permeability transition causes outer
      membrane rupture, the findings, therefore, dissociate these two events, implying
      that Bax uses an alternative mechanism for triggering release of Cyt c from
      mitochondria.

PMID- 9560218
TI  - Transmembrane heme delivery systems.
AB  - Heme proteins play pivotal roles in a wealth of biological processes. Despite
      this, the molecular mechanisms by which heme traverses bilayer membranes for use
      in biosynthetic reactions are unknown. The biosynthesis of c-type cytochromes
      requires that heme is transported to the bacterial periplasm or mitochondrial
      intermembrane space where it is covalently ligated to two reduced cysteinyl
      residues of the apocytochrome. Results herein suggest that a family of integral
      membrane proteins in prokaryotes, protozoans, and plants act as transmembrane
      heme delivery systems for the biogenesis of c-type cytochromes. The complete
      topology of a representative from each of the three subfamilies was
      experimentally determined. Key histidinyl residues and a conserved tryptophan
      rich region (designated the WWD domain) are positioned at the site of cytochrome
      c assembly for all three subfamilies. These histidinyl residues were shown to be
      essential for function in one of the subfamilies, an ABC transporter encoded by
      helABCD. We believe that a directed heme delivery pathway is vital for the
      synthesis of cytochromes c, whereby heme iron is protected from oxidation via
      ligation to histidinyl residues within the delivery proteins.

PMID- 9560219
TI  - Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich
      cell edges.
AB  - Stimulation of endothelial cells (ECs) with ATP evoked an increase in
      intracellular Ca2+ concentration ([Ca2+]i). In a single bovine aortic EC, the
      [Ca2+]i rise started at a specific peripheral locus and propagated throughout the
      entire cell as a Ca2+ wave. The initiation locus was constant upon repeated
      stimulation with ATP or other agonists (bradykinin and thrombin). The Ca2+ wave
      was unaffected by the removal of extracellular Ca2+, demonstrating its dependence
      on intracellular Ca2+ release. Microinjection of heparin into the cell inhibited
      the ATP-induced Ca2+ responses, indicating that the Ca2+ wave is at least partly
      mediated by the inositol 1,4, 5-trisphosphate receptor. Immunofluorescence
      staining revealed that caveolin, a marker protein for caveolae, is distributed
      heterogeneously in the cell and that Ca2+ waves preferentially originate at
      caveolin-rich cell edges. In contrast to caveolin, internalized transferrin and
      subunits of the clathrin-associated adaptor complexes such as adaptor protein-1
      and -2 were diffusely distributed. Disruption of microtubules by Colcemid led to
      redistribution of caveolin away from the edges into the perinuclear center of the
      cell, and the ATP-induced [Ca2+]i increase was initiated on the rim of the
      centralized caveolin. Thus, caveolae may be involved in the initiation of ATP
      induced Ca2+ waves in ECs.

PMID- 9560220
TI  - Association of calcium channel alpha1S and beta1a subunits is required for the
      targeting of beta1a but not of alpha1S into skeletal muscle triads.
AB  - The skeletal muscle L-type Ca2+ channel is a complex of five subunits that is
      specifically localized in the triad. Its primary function is the rapid activation
      of Ca2+ release from cytoplasmic stores in a process called excitation
      contraction coupling. To study the role of alpha1S-beta1a interactions in the
      incorporation of the functional channel complex into the triad, alpha1S and
      beta1a [or a beta1a-green fluorescent protein (GFP) fusion protein] were
      expressed alone and in combination in myotubes of the dysgenic cell line GLT.
      betaGFP expressed in dysgenic myotubes that lack the skeletal muscle alpha1S
      subunit was diffusely distributed in the cytoplasm. On coexpression with the
      alpha1S subunit betaGFP distribution became clustered and colocalized with
      alpha1S immunofluorescence. Based on the colocalization of betaGFP and alpha1S
      with the ryanodine receptor the clusters were identified as T-tubule/sarcoplasmic
      reticulum junctions. Expression of alpha1S with and without beta1a restored Ca2+
      currents and depolarization-induced Ca2+ release. The translocation of betaGFP
      from the cytoplasm into the junctions failed when betaGFP was coexpressed with
      alpha1S mutants in which the beta interaction domain had been altered (alpha1S
      Y366S) or deleted (alpha1S-Delta351-380). Although alpha1S-Y366S did not
      associate with betaGFP it was incorporated into the junctions, and it restored
      Ca2+ currents and depolarization-induced Ca2+ release. Thus, beta1a requires the
      association with the beta interaction domain in the I-II cytoplasmic loop of
      alpha1S for its own incorporation into triad junctions, but stable alpha1S-beta1a
      association is not necessary for the targeting of alpha1S into the triads or for
      its normal function in Ca2+ conductance and excitation-contraction coupling.

PMID- 9560221
TI  - A distinct cyclin-dependent kinase-activating kinase of Arabidopsis thaliana.
AB  - The activation of cyclin-dependent kinases (CDKs) requires phosphorylation of a
      threonine residue within the T-loop catalyzed by CDK-activating kinases (CAKs).
      Thus far no functional CAK homologue has been reported in plants. We screened an
      Arabidopsis cDNA expression library for complementation of a budding yeast CAK
      mutant. A cDNA, cak1At, was isolated that suppressed the CAK mutation in budding
      yeast, and it also complemented a fission yeast CAK mutant. cak1At encodes a
      protein related to animal CAKs. The CAK similarity was restricted to the
      conserved kinase domains, leading to classification of Cak1At as a distinct CDK
      in the phylogenetic tree. Immunoprecipitates with the anti-Cak1At antibody
      phosphorylated human CDK2 at the threonine residue (T160) within the T-loop and
      activated its activity to phosphorylate histone H1. Whereas CAKs in animals and
      fission yeast are involved in regulation of the cell cycle and basal
      transcription by phosphorylating the carboxyl-terminal domain (CTD) of the
      largest subunit of RNA polymerase II, Cak1At did not phosphorylate the CTD. An
      Arabidopsis CTD-kinase isolated separately from Cak1At was shown to interact with
      the yeast protein p13(suc1), but it had no CDK2-kinase activity. Therefore, the
      CTD of RNA polymerase II is probably phosphorylated by a Cdc2-related kinase
      distinct from Cak1At. cak1At is a single-copy gene in Arabidopsis and is highly
      expressed in proliferating cells of suspension cultures.

PMID- 9560222
TI  - A cytoplasmic protein, bystin, interacts with trophinin, tastin, and cytokeratin
      and may be involved in trophinin-mediated cell adhesion between trophoblast and
      endometrial epithelial cells.
AB  - Trophinin and tastin form a cell adhesion molecule complex that potentially
      mediates an initial attachment of the blastocyst to uterine epithelial cells at
      the time of implantation. Trophinin and tastin, however, do not directly bind to
      each other, suggesting the presence of an intermediary protein. The present study
      identifies a cytoplasmic protein, named bystin, that directly binds trophinin and
      tastin. Bystin consists of 306 amino acid residues and is predicted to contain
      tyrosine, serine, and threonine residues in contexts conforming to motifs for
      phosphorylation by protein kinases. Database searches revealed a 53% identity of
      the predicted peptide sequence with the Drosophila bys (mrr) gene. Direct protein
      protein interactions of trophinin, tastin, and bystin analyzed by yeast two
      hybrid assays and by in vitro protein binding assays indicated that binding
      between bystin and trophinin and between bystin and tastin is enhanced when
      cytokeratin 8 and 18 are present as the third molecule. Immunocytochemistry of
      bystin showed that bystin colocalizes with trophinin, tastin, and cytokeratins in
      a human trophoblastic teratocarcinoma cell, HT-H. It is therefore possible that
      these molecules form a complex and thus are involved in the process of embryo
      implantation.

PMID- 9560223
TI  - Targeted disruption of p70(s6k) defines its role in protein synthesis and
      rapamycin sensitivity.
AB  - Here, we disrupted the p70 S6 kinase (p70(s6k)) gene in murine embryonic stem
      cells to determine the role of this kinase in cell growth, protein synthesis, and
      rapamycin sensitivity. p70(s6k-/-) cells proliferated at a slower rate than
      parental cells, suggesting that p70(s6k) has a positive influence on cell
      proliferation but is not essential. In addition, rapamycin inhibited
      proliferation of p70(s6k-/-) cells, indicating that other events inhibited by the
      drug, independent of p70(s6k), also are important for both cell proliferation and
      the action of rapamycin. In p70(s6k-/-) cells, which exhibited no ribosomal S6
      phosphorylation, translation of mRNA encoding ribosomal proteins was not
      increased by serum nor specifically inhibited by rapamycin. In contrast,
      rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E
      BP1), general mRNA translation, and overall protein synthesis in p70(s6k-/-)
      cells, indicating that these events proceed independently of p70(s6k) activity.
      This study localizes the function of p70(s6k) to ribosomal biogenesis by
      regulating ribosomal protein synthesis at the level of mRNA translation.

PMID- 9560224
TI  - Cellular memory: neutrophil orientation reverses during temporally decreasing
      chemoattractant concentrations.
AB  - Cell directional orientation or shape polarization is the first cellular step in
      neutrophil locomotion. To better understand how chemoattractants interact with
      cells, we studied neutrophil polarization (or shape changes) during exposure to a
      temporally decreasing chemoattractant signal of N-formyl-methionyl-leucyl
      phenylalanine (FMLP) in the absence of a spatial concentration gradient. To
      accomplish this objective, we used a manifold of differing FMLP concentrations
      attached to a stopped-flow microscope chamber. Spatial gradients of a fluorescent
      chemotactic peptide could not be detected in the chamber by using
      microfluorometry. When FMLP was injected at continually increasing concentrations
      at 10-s intervals, the shape and relative direction of the neutrophil persisted.
      However, when temporally decreasing FMLP concentrations were injected,
      approximately 80% of the cells changed their direction with 44% of the total
      cells swinging about to 180 degrees +/- 15 degrees. Most of these directional
      changes involved dissolution of both the lamellipodium and uropod and reformation
      of these structures 180 degrees from their original positions. This research
      suggests that neutrophils reverse their morphological polarity when exposed to
      temporally decreasing ligand concentrations by "remembering" their ligand
      exposure history and relative direction.

PMID- 9560225
TI  - Macrophages resistant to endogenously generated nitric oxide-mediated apoptosis
      are hypersensitive to exogenously added nitric oxide donors: dichotomous
      apoptotic response independent of caspase 3 and reversal by the mitogen-activated
      protein kinase kinase (MEK) inhibitor PD 098059.
AB  - Nitric oxide (NO) induction through the inducible NO synthase has been
      demonstrated to cause cell death in macrophages. We demonstrate that, in
      macrophages that have been rendered resistant to apoptosis induced by inducible
      NO synthase (RES cells), exposure to exogenous NO donors results in a
      hypersensitive apoptosis reaction when compared with the parental RAW 264.7
      cells. The apoptosis induced via exogenous NO donors was found to be caspase 3
      independent. Although caspase 3 activity was stimulated in the apoptotic
      macrophages, inhibition of caspase 3 by the inhibitor DEVD-CHO (N-acetyl-Asp-Glu
      Val-Asp-aldehyde) did not reverse the apoptosis induced by the NO donor S
      nitrosoglutathione (GSNO). This suggests that although caspase 3 activity is
      stimulated during apoptosis in macrophages, this signal is not sufficient to
      induce apoptosis. Cleavage of the enzyme poly(ADP ribose) polymerase mirrors our
      results of the caspase activity. Interestingly, we show that exogenous NO
      donation results in an accumulation of cells at the G2/M-phase border. Here, we
      demonstrate that the mitogen activated protein kinase kinase (MEK) inhibitor PD
      098059 can be used to reverse the G2/M-phase block and show that this treatment
      also inhibits the observed apoptosis in RES macrophages. Treatment with the MEK
      inhibitor also reversed both the caspase 3 activity and poly(ADP ribose)
      polymerase cleavage in cells treated with GSNO. This result indicates that the
      mitogen-activated protein kinase pathway may be involved in regulation of the
      caspase cascade. Alternatively, it may suggest an activity for the MEK inhibitor
      heretofore not observed, that of a cyclin kinase inhibitor. Our results suggest
      that selection of macrophages by resistance to endogenously generated NO may
      cause hypersensitivity to exogenous NO donors. These findings have relevant
      implications for the treatment of apoptotic-resistant cell populations that may
      occur in both cancer and atheroma.

PMID- 9560226
TI  - Activation of protein tyrosine kinase PYK2 by the m1 muscarinic acetylcholine
      receptor.
AB  - Several G protein-coupled receptors are known to direct the tyrosine
      phosphorylation, and in some cases the activation, of diverse tyrosine kinases.
      Using a stable cell line approach, we characterize the activation of PYK2, a
      tyrosine kinase structurally related to focal adhesion kinase, by the G protein
      coupled m1 muscarinic acetylcholine receptor. We find that PYK2 tyrosine kinase
      activity is critical for the m1 receptor-stimulated tyrosine phosphorylation of
      PYK2. Furthermore, we identify two tyrosine residues that are subject to
      phosphorylation in response to muscarinic signaling and show that this
      phosphorylation induces two cytosolic proteins, c-Src and Grb2, to bind to PYK2.
      This is the first demonstration of the significance played by distinct PYK2
      tyrosine residues in G protein-coupled signaling to this kinase. By comparison,
      though m1 receptors induce the tyrosine phosphorylation of the cytoskeletal
      protein paxillin, the association of paxillin with PYK2 is unaffected by
      muscarinic signaling. We also provide evidence that PYK2 specifically
      phosphorylates the carboxyl-terminal cytosolic portion of the potassium channel
      Kv1.2 in a manner regulated by the m1 receptor. These results delineate molecular
      events attending the m1 muscarinic receptor stimulation of this tyrosine kinase
      and establish PYK2 as an effector of the m1 muscarinic receptor in the regulation
      of multiple cell functions.

PMID- 9560227
TI  - Sequestration of the G protein beta gamma subunit complex inhibits receptor
      mediated endocytosis.
AB  - Cell surface receptors that mediate endocytosis cluster into clathrin-coated
      pits, which pinch off to form vesicles that transport the receptors and their
      ligands. This multi-step process requires the coordinated action of many factors,
      including GTP-hydrolyzing proteins such as dynamin and regulators of actin
      cytoskeleton assembly. We note herein that sequestration of heterotrimeric G
      protein beta gamma subunits in intact cells strongly inhibits clathrin-coated pit
      mediated endocytosis and causes rearrangement of the actin cytoskeleton. Our
      results suggest that cells contain a pool of free beta gamma and that it
      functions constitutively to permit endocytosis.

PMID- 9560229
TI  - Solution structure of SpoIIAA, a phosphorylatable component of the system that
      regulates transcription factor sigmaF of Bacillus subtilis.
AB  - The establishment of differential gene expression in sporulating Bacillus
      subtilis involves four protein components, one of which, SpoIIAA, undergoes
      phosphorylation and dephosphorylation. We have used NMR spectroscopy to determine
      the solution structure of the nonphosphorylated form of SpoIIAA. The structure
      shows a fold consisting of a four-stranded beta-sheet and four alpha-helices.
      Knowledge of the structure helps to account for the phenotype of several strains
      of B. subtilis that carry known spoIIAA mutations and should facilitate
      investigations of the conformational consequences of phosphorylation.

PMID- 9560228
TI  - Activation of apurinic/apyrimidinic endonuclease in human cells by reactive
      oxygen species and its correlation with their adaptive response to genotoxicity
      of free radicals.
AB  - Apurinic/apyrimidinic (AP) endonuclease (APE; EC 4.2.99.18) plays a central role
      in repair of DNA damage due to reactive oxygen species (ROS) because its DNA 3'
      phosphoesterase activity removes 3' blocking groups in DNA that are generated by
      DNA glycosylase/AP-lyases during removal of oxidized bases and by direct ROS
      reaction with DNA. The major human APE (APE-1) gene is activated selectively by
      sublethal levels of a variety of ROS and ROS generators, including ionizing
      radiation, but not by other genotoxicants-e.g., UV light and alkylating agents.
      Increased expression of APE mRNA and protein was observed both in the HeLa S3
      tumor line and in WI 38 primary fibroblasts, and it was accompanied by
      translocation of the endonuclease to the nucleus. ROS-treated cells showed a
      significant increase in resistance to the cytotoxicity of such ROS generators as
      H2O2 and bleomycin, but not to UV light. This "adaptive response" appears to
      result from enhanced repair of cytotoxic DNA lesions due to an increased activity
      of APE-1, which may be limiting in the base excision repair process for ROS
      induced toxic lesions.

PMID- 9560230
TI  - Rescue of Caenorhabditis elegans pharyngeal development by a vertebrate heart
      specification gene.
AB  - Development of pharyngeal muscle in nematodes and cardiac muscle in vertebrates
      and insects involves the related homeobox genes ceh-22, nkx2.5, and tinman,
      respectively. To determine whether the nematode and vertebrate genes perform
      similar functions, we examined activity of the zebrafish nkx2.5 gene in
      transgenic Caenorhabditis elegans. Here, we report that ectopic expression of
      nkx2.5 in C. elegans body wall muscle can directly activate expression of both
      the endogenous myo-2 gene, a ceh-22 target normally expressed only in pharyngeal
      muscle, and a synthetic reporter construct controlled by a multimerized CEH-22
      binding site. nkx2.5 also efficiently rescues a ceh-22 mutant when expressed in
      pharyngeal muscle. Together, these results indicate that nkx2.5 and ceh-22
      provide a single conserved molecular function. Further, they suggest that an
      evolutionarily conserved mechanism underlies heart development in vertebrates and
      insects and pharyngeal development in nematodes.

PMID- 9560231
TI  - A paracrine role for the epithelial progesterone receptor in mammary gland
      development.
AB  - Recently generated progesterone receptor (PR)-negative (PR-/-) mice provide an
      excellent model for dissecting the role of progesterone in the development of the
      mammary gland during puberty and pregnancy. However, the full extent of the
      mammary gland defect in these mice caused by the absence of the PR cannot be
      assessed, because PR-/- mice do not exhibit estrous cycles and fail to become
      pregnant. To circumvent this difficulty, we have transplanted PR-/- breasts into
      wild-type mice, and we have demonstrated that the development of the mammary
      gland in the absence of the PR is arrested at the stage of the simple ductal
      system found in the young virgin mouse. Mammary transplants lacking the PR in the
      stromal compartment give rise to normal alveolar growth, whereas transplants
      containing PR-/- epithelium conserve the abnormal phenotype. Chimeric epithelia
      in which PR-/- cells are in close vicinity to PR wild-type cells go through
      complete alveolar development to which the PR-/- cells contribute. Together,
      these results indicate that progesterone acts by a paracrine mechanism on a
      subset of mammary epithelial cells to allow for alveolar growth and that
      expression of the PR is not required in all the cells of the mammary epithelium
      in order for alveolar development to proceed normally.

PMID- 9560232
TI  - Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role
      for FGF signaling in pregastrulation mammalian development.
AB  - We disrupted the fibroblast growth factor (FGF) receptor 2 (FGFR2) gene by
      introducing a neo cassette into the IIIc ligand binding exon and by deleting a
      genomic DNA fragment encoding its transmembrane domain and part of its kinase I
      domain. A recessive embryonic lethal mutation was obtained. Preimplantation
      development was normal until the blastocyst stage. Homozygous mutant embryos died
      a few hours after implantation at a random position in the uterine crypt, with
      collapsed yolk cavity. Mutant blastocysts hatched, adhered, and formed a layer of
      trophoblast giant cells in vitro, but after prolonged culture, the growth of the
      inner cell mass stopped, no visceral endoderm formed, and finally the egg
      cylinder disintegrated. It follows that FGFR2 is required for early
      postimplantation development between implantation and the formation of the egg
      cylinder. We suggest that FGFR2 contributes to the outgrowth, differentiation,
      and maintenance of the inner cell mass and raise the possibility that this
      activity is mediated by FGF4 signals transmitted by FGFR2. The role of early FGF
      signaling in pregastrulation development as a possible adaptation to mammalian
      (amniote) embryogenesis is discussed.

PMID- 9560233
TI  - The role of robustness and changeability on the origin and evolution of genetic
      codes.
AB  - We propose that an essential factor on the origin of genetic codes is a balanced
      accomplishment of robustness and changeability, two antithetical, but
      fundamental, properties for the survival and evolution of organisms. These
      measures are defined as the intrinsic properties of genetic codes. An evaluation
      of these properties explains the structural regularity of genetic codes,
      estimates the order of codon reassignment in deviant codes, and predicts the most
      probable deviant codes that exist. The enumeration of genetic codes that could
      have evolved from the standard genetic code under the selection pressure on
      robustness and changeability strongly limits the freedom of codon reassignments.
      The codon reassignments of all currently known deviant genetic codes belong to
      this predicted evolutionary path, and they generally give the highest
      improvements on robustness and changeability.

PMID- 9560234
TI  - Toward a resolution of the introns early/late debate: only phase zero introns are
      correlated with the structure of ancient proteins.
AB  - We present evidence that a well defined subset of intron positions shows a non
      random distribution in ancient genes. We analyze a database of ancient conserved
      regions drawn from GenBank 101 to retest two predictions of the theory that the
      first genes were constructed by exon shuffling. These predictions are that there
      should be an excess of symmetric exons (and sets of exons) flanked by introns of
      the same phase (positions within the codon) and that intron positions in ancient
      proteins should correlate with the boundaries of compact protein modules. Both
      these predictions are supported by the data, with considerable statistical force
      (P values < 0.0001). Intron positions correlate to modules of diameters around
      21, 27, and 33 A, and this correlation is due to phase zero introns. We suggest
      that 30-40% of present day intron positions in ancient genes correspond to phase
      zero introns originally present in the progenote, while almost all of the
      remaining intron positions correspond to introns added, or moved, appearing
      equally in all three intron phases. This proposal provides a resolution for many
      of the arguments of the introns-early/introns-late debate.

PMID- 9560235
TI  - Signaling among relatives. III. Talk is cheap.
AB  - The Sir Philip Sidney game has been used by numerous authors to show how signal
      cost can facilitate honest signaling among relatives. Here, we demonstrate that,
      in this game, honest cost-free signals are possible as well, under very general
      conditions. Moreover, these cost-free signals are better for all participants
      than the previously explored alternatives. Recent empirical evidence suggests
      that begging is energetically inexpensive for nestling birds; this finding led
      some researchers to question the applicability of the costly signaling framework
      to nestling begging. Our results show that cost-free or inexpensive signals, as
      observed empirically, fall within the framework of signaling theory.

PMID- 9560236
TI  - Runaway ornament diversity caused by Fisherian sexual selection.
AB  - Fisher's runaway process of sexual selection is potentially an important force
      generating character divergence between closely related populations. We
      investigated the evolution of multiple female preferences by Fisher's runaway
      process. There are two outcomes of runaway. The first is the evolution of mate
      preference to a stable equilibrium. This evolution occurs if the benefits of mate
      choice are sufficiently large relative to the cost of choice. Alternatively, mate
      preferences evolve cyclically. The rate and pattern of cyclic evolution depends
      primarily on the individual cost of choice and epistasis in the joint cost of
      choice. If there are small differences in natural selection (e.g., predation
      risk) between populations, cyclic evolution quickly leads to divergence in mate
      preferences and sexual ornaments and so to sexual isolation.

PMID- 9560237
TI  - Diploid hybrid speciation in Penstemon (Scrophulariaceae).
AB  - Hybrid speciation has played a significant role in the evolution of angiosperms
      at the polyploid level. However, relatively little is known about the importance
      of hybrid speciation at the diploid level. Two species of Penstemon have been
      proposed as diploid hybrid derivatives based on morphological data, artificial
      crossing studies, and pollinator behavior observations: Penstemon spectabilis
      (derived from hybridization between Penstemon centranthifolius and Penstemon
      grinnellii) and Penstemon clevelandii (derived from hybridization between P.
      centranthifolius and P. spectabilis). Previous studies were inconclusive
      regarding the purported hybrid nature of these species because of a lack of
      molecular markers sufficient to differentiate the parental taxa in the hybrid
      complex. We developed hypervariable nuclear markers using inter-simple sequence
      repeat banding patterns to test these classic hypotheses of diploid hybrid
      speciation in Penstemon. Each species in the hybrid complex was genetically
      distinct, separated by 10-42 species-specific inter-simple sequence repeat
      markers. Our data do not support the hybrid origin of P. spectabilis but clearly
      support the diploid hybrid origin of P. clevelandii. Our results further suggest
      that the primary reason diploid hybrid speciation is so difficult to detect is
      the lack of molecular markers able to differentiate parental taxa from one
      another, particularly with recently diverged species.

PMID- 9560238
TI  - Separation of killing and tumorigenic effects of an alkylating agent in mice
      defective in two of the DNA repair genes.
AB  - Alkylation of DNA at the O6-position of guanine is one of the most critical
      events leading to mutation, cancer, and cell death. The enzyme O6-methylguanine
      DNA methyltransferase repairs O6-methylguanine as well as a minor methylated
      base, O4-methylthymine, in DNA. Mouse lines deficient in the methyltransferase
      (MGMT) gene are hypersensitive to both the killing and to the tumorigenic effects
      of alkylating agents. We now show that these dual effects of an alkylating agent
      can be dissociated by introduction of an additional defect in mismatch repair.
      Mice with mutations in both alleles of the MGMT gene and one of the mismatch
      repair genes, MLH1, are as resistant to methylnitrosourea (MNU) as are wild-type
      mice, in terms of survival, but do have numerous tumors after receiving MNU. In
      contrast to MGMT-/- MLH1(+/+) mice with decrease in size of the thymus and
      hypocellular bone marrow after MNU administration, no conspicuous change was
      found in MGMT-/- MLH1(-/-) mice treated in the same manner. Thus, killing and
      tumorigenic effects of an alkylating agent can be dissociated by preventing
      mismatch repair pathways.

PMID- 9560239
TI  - Modification of bacterial artificial chromosomes through chi-stimulated
      homologous recombination and its application in zebrafish transgenesis.
AB  - The modification of yeast artificial chromosomes through homologous recombination
      has become a useful genetic tool for studying gene function and enhancer/promoter
      activity. However, it is difficult to purify intact yeast artificial chromosome
      DNA at a concentration sufficient for many applications. Bacterial artificial
      chromosomes (BACs) are vectors that can accommodate large DNA fragments and can
      easily be purified as plasmid DNA. We report herein a simple procedure for
      modifying BACs through homologous recombination using a targeting construct
      containing properly situated Chi sites. To demonstrate a usage for this
      technique, we modified BAC clones containing the zebrafish GATA-2 genomic locus
      by replacing the first coding exon with the green fluorescent protein (GFP)
      reporter gene. Molecular analyses confirmed that the modification occurred
      without additional deletions or rearrangements of the BACs. Microinjection
      demonstrated that GATA-2 expression patterns can be recapitulated in living
      zebrafish embryos by using these GFP-modified GATA-2 BACs. Embryos microinjected
      with the modified BAC clones were less mosaic and had improved GFP expression in
      hematopoietic progenitor cells compared with smaller plasmid constructs. The
      precise modification of BACs through Chi-stimulated homologous recombination
      should be useful for studying gene function and regulation in cultured cells or
      organisms where gene transfer is applicable.

PMID- 9560240
TI  - Tight clustering and hemizygosity of apomixis-linked molecular markers in
      Pennisetum squamulatum implies genetic control of apospory by a divergent locus
      that may have no allelic form in sexual genotypes.
AB  - Apomixis is a naturally occurring mode of reproduction that results in embryo
      formation without the involvement of meiosis or fertilization of the egg. Seed
      derived progeny of an apomictic plant are genetically identical to the maternal
      parent. We are studying a form of apomixis called apospory that occurs in the
      genus Pennisetum, a taxon in the grass family. A cultivated member of this genus,
      pearl millet (Pennisetum glaucum), reproduces sexually. A wild relative of pearl
      millet, Pennisetum squamulatum, that is an obligate aposporous species, is cross
      compatible with pearl millet when used as a pollen donor in the interspecific
      cross. We present herein the genetic mapping of 13 molecular markers in an
      interspecific hybrid population of 397 individuals that segregates for apomixis
      and sexuality. Surprisingly, 12 of the 13 markers strictly cosegregated with
      aposporous embryo sac development, clearly defining a contiguous apospory
      specific genomic region in which no genetic recombination was detected. Lack of
      or suppression of recombination may be coincidentally associated with the
      chromosomal context of the apomixis locus or it may be a consequence of its
      evolution that is essential for preservation of gene function as has been
      previously shown in studies of complex loci in both plant and animal species.

PMID- 9560241
TI  - Reactivation of XIST in normal fibroblasts and a somatic cell hybrid: abnormal
      localization of XIST RNA in hybrid cells.
AB  - The XIST gene, expressed only from the inactive X chromosome, is a critical
      component of X inactivation. Although apparently unnecessary for maintenance of
      inactivation, XIST expression is thought to be sufficient for inactivation of
      genes in cis even when XIST is located abnormally on another chromosome. This
      repression appears to involve the association of XIST RNA with the chromosome
      from which it is expressed. Reactivated genes on the inactive X chromosome,
      however, maintain expression in several somatic cell hybrid lines with stable
      expression of XIST. We describe here another example of an XIST-expressing human
      hamster hybrid that lacks X-linked gene repression in which the human XIST gene
      present on an active X chromosome was reactivated by treatment with 5-aza-2'
      deoxycytidine. These data raise the possibility that human XIST RNA does not
      function properly in human-rodent somatic cell hybrids. As part of our approach
      to address this question, we reactivated the XIST gene in normal male fibroblasts
      and then compared their patterns of XIST RNA localization by subcellular
      fractionation and in situ hybridization with those of hybrid cells. Although XIST
      RNA is nuclear in all cell types, we found that the in situ signals are much more
      diffuse in hybrids than in human cells. These data suggest that hybrids lack
      components needed for XIST localization and, presumably, XIST-mediated gene
      repression.

PMID- 9560242
TI  - A role for Pak protein kinases in Schwann cell transformation.
AB  - Neurofibromatosis type 1 (NF1), a common autosomal dominant disorder caused by
      loss of the NF1 gene, is characterized clinically by neurofibromas and more
      rarely by neurofibrosarcomas. Neurofibromin, the protein encoded by NF1,
      possesses an intrinsic GTPase accelerating activity for the Ras proto-oncogene.
      Through this activity, it is a negative regulator of Ras. The Pak protein kinase
      is a candidate for a downstream signaling protein that may mediate Ras signals
      because it is activated by Rac and Cdc42, two small G proteins required for Ras
      signaling. Here, we use Pak mutants to explore the role of Pak in Ras signaling
      in Schwann cells, the cells affected in NF1. Whereas an activated Pak mutant does
      not transform cells, dominant negative Pak mutants are potent inhibitors of Ras
      transformation of rat Schwann cells and of a neurofibrosarcoma cell line from an
      NF1 patient. Although activated Pak stimulated jun-N-terminal kinase, inhibition
      of Ras transformation by dominant negative Pak did not require inhibition of jun
      N-terminal kinase. Instead, the Pak mutants appeared to inhibit transformation by
      preventing Ras activation of the ERK/mitogen-activated protein kinase cascade.
      These results have implications for our understanding of NF1 because a
      neurofibrosarcoma cell line derived from a patient with NF1 was reverted by
      stable expression of the Pak dominant negative mutants.

PMID- 9560243
TI  - Evolution of rhizobia by acquisition of a 500-kb symbiosis island that integrates
      into a phe-tRNA gene.
AB  - Nodulation and nitrogen fixation genes of Mesorhizobium loti are encoded on the
      chromosome of the bacterium. Nevertheless, there is strong evidence that these
      genes can be transferred from an inoculant strain to nonsymbiotic mesorhizobia in
      the field environment. Here we report that the chromosomal symbiotic element of
      M. loti strain ICMP3153 is transmissible in laboratory matings to at least three
      genomic species of nonsymbiotic mesorhizobia. The element is 500 kb in size,
      integrates into a phe-tRNA gene, and encodes an integrase of the phage P4 family
      just within its left end. The entire phe-tRNA gene is reconstructed at the left
      end of the element upon integration, whereas the 3' 17 nucleotides of the tRNA
      gene are present as a direct repeat at the right end. We termed the element a
      symbiosis island on the basis of its many similarities to pathogenicity islands.
      It may represent a class of genetic element that contributes to microbial
      evolution by acquisition.

PMID- 9560244
TI  - Monosomy of a specific chromosome determines L-sorbose utilization: a novel
      regulatory mechanism in Candida albicans.
AB  - We report the identification of the gene, SOU1, required for L-sorbose
      assimilation in Candida albicans. The level of the expression of SOU1 is
      determined by the copy number of chromosome III (also denoted chromosome 5), such
      that monosomic strains assimilate L-sorbose, whereas disomic strains do not, in
      spite of the fact that SOU1 is not on this chromosome. We suggest that C.
      albicans contains a resource of potentially beneficial genes that are activated
      by changes in chromosome number, and that this elaborate mechanism regulates the
      utilization of food supplies and possibly other important functions, thus
      representing a novel general means for regulating gene expression in microbes.

PMID- 9560245
TI  - ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that
      interacts selectively with caspases.
AB  - We have identified and characterized ARC, apoptosis repressor with caspase
      recruitment domain (CARD). Sequence analysis revealed that ARC contains an N
      terminal CARD fused to a C-terminal region rich in proline/glutamic acid
      residues. The CARD domain of ARC exhibited significant homology to the prodomains
      of apical caspases and the CARDs present in the cell death regulators Apaf-1 and
      RAIDD. Immunoprecipitation analysis revealed that ARC interacts with caspase-2, 
      8, and Caenorhabditis elegans CED-3, but not with caspase-1, -3, or -9. ARC
      inhibited apoptosis induced by caspase-8 and CED-3 but not that mediated by
      caspase-9. Further analysis showed that the enzymatic activity of caspase-8 was
      inhibited by ARC in 293T cells. Consistent with the inhibition of caspase-8, ARC
      attenuated apoptosis induced by FADD and TRADD and that triggered by stimulation
      of death receptors coupled to caspase-8, including CD95/Fas, tumor necrosis
      factor-R1, and TRAMP/DR3. Remarkably, the expression of human ARC was primarily
      restricted to skeletal muscle and cardiac tissue. Thus, ARC represents an
      inhibitor of apoptosis expressed in muscle that appears to selectively target
      caspases. Delivery of ARC by gene transfer or enhancement of its endogenous
      activity may provide a strategy for the treatment of diseases that are
      characterized by inappropriately increased cell death in muscle tissue.

PMID- 9560246
TI  - Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for
      human Hirschsprung disease.
AB  - The spontaneous mouse mutant Dominant megacolon (Dom) is a valuable model for the
      study of human congenital megacolon (Hirschsprung disease). Here we report that
      the defect in the Dom mouse is caused by mutation of the gene encoding the Sry
      related transcription factor Sox10. This assignment is based on (i)
      colocalization of the Sox10 gene with the Dom mutation on chromosome 15; (ii)
      altered Sox10 expression in the gut and in neural-crest derived structures of
      cranial ganglia of Dom mice; (iii) presence of a frameshift in the Sox10 coding
      region, and (iv) functional inactivation of the resulting truncated protein.
      These results identify the transcriptional regulator Sox10 as an essential factor
      in mouse neural crest development and as a further candidate gene for human
      Hirschsprung disease, especially in cases where it is associated with features of
      Waardenburg syndrome.

PMID- 9560247
TI  - An oncogenic form of p53 confers a dominant, gain-of-function phenotype that
      disrupts spindle checkpoint control.
AB  - Although it is well-established that p53 functions as a tumor suppressor gene,
      certain mutations exhibit gain-of-function activities that increase oncogenic
      transformation. We have found a common class of p53 missense mutation that
      exhibits a dominant, gain-of-function activity that generates genomic
      instability. Fibroblasts from Li-Fraumeni syndrome heterozygotes with such
      mutations generate polyploid cells when exposed to spindle depolymerizing agents.
      Expression of such mutant alleles in normal fibroblasts yields the same
      phenotype. This class of dominant, gain-of-function p53 mutation (p53(RSC),
      relaxed spindle checkpoint allele) does not require the transcriptional
      activation function of p53 for this behavior. Thus p53 mutations can contribute
      to progression of a cancer cell not only by absence of p53 tumor suppressor
      activity but also by the presence of an activity that promotes genetic
      instability.

PMID- 9560248
TI  - Homology-directed repair is a major double-strand break repair pathway in
      mammalian cells.
AB  - Mammalian cells have been presumed to repair potentially lethal chromosomal
      double-strand breaks (DSBs) in large part by processes that do not require
      homology to the break site. This contrasts with Saccharomyces cerevisiae where
      the major DSB repair pathway is homologous recombination. Recently, it has been
      determined that DSBs in genomic DNA in mammalian cells can stimulate homologous
      recombination as much as 3 or 4 orders of magnitude, suggesting that homology
      directed repair may play an important role in the repair of chromosomal breaks.
      To determine whether mammalian cells use recombinational repair at a significant
      level, we have analyzed the spectrum of repair events at a defined chromosomal
      break by using direct physical analysis of repair products. When an endonuclease
      generated DSB is introduced into one of two direct repeats, homologous repair is
      found to account for 30-50% of observed repair events. Both noncrossover and
      deletional homologous repair products are detected, at approximately a 1:3 ratio.
      These results demonstrate the importance of homologous recombination in the
      repair of DSBs in mammalian cells. In the remaining observed repair events, DSBs
      are repaired by nonhomologous processes. The nonhomologous repair events
      generally result in small deletions or insertions at the break site, although a
      small fraction of events result in larger chromosomal rearrangements.
      Interestingly, in two insertions, GT repeats were integrated at one of the broken
      chromosome ends, suggesting that DSB repair can contribute to the spread of
      microsatellite sequences in mammalian genomes.

PMID- 9560249
TI  - Putative pheromone receptors related to the Ca2+-sensing receptor in Fugu.
AB  - By a combination of PCR with degenerate primers and low stringency probing, we
      have isolated a large family of genes related to the Ca2+-sensing receptor from
      the genome of Fugu rubripes. One of the genes (type I) is the Fugu homologue of
      the Ca2+-sensing receptor. The remaining genes can be divided into five classes
      (type II-VI) on the bases of gene structure. In several types, the genes occur in
      clusters as tandem arrays. These genes appear to be the homologues of the
      vomeronasal pheromone receptors recently described in rodents. The Fugu genes are
      expressed in the tissues of the nose, suggesting that they may have a similar
      physiological role.

PMID- 9560250
TI  - Transposition of the mariner element from Drosophila mauritiana in zebrafish.
AB  - With the increased popularity of zebrafish (Danio rerio) for mutagenesis studies,
      efficient methods for manipulation of its genome are needed. One approach is the
      use of a transposable element as a vector for gene transfer in this species. We
      report here the transformation of zebrafish and germ-line transmission of the
      mariner element from Drosophila mauritiana. The mariner element was selected
      because its transposition is independent of host-specific factors. One- to two
      cell-stage zebrafish embryos were coinjected with a supercoiled plasmid carrying
      the nonautonomous mariner element peach and mRNA encoding the transposase.
      Surviving larvae were reared to adulthood, and the transmission of peach to the
      F1 generation was tested by PCR. Four of the 12 founders, following plasmid
      injections on 2 different days, transmitted the element to their progeny.
      Inheritance of the transgene from the F1 to the F2 generation showed a Mendelian
      pattern. No plasmid sequences were detected by PCR or Southern blot analysis,
      indicating transposition of peach rather than random integration of the plasmid
      DNA. These data provide evidence of transformation of a vertebrate with a
      transposable element and support the host-independent mechanism for transposition
      of the mariner element. We suggest this system could be used for insertional
      mutagenesis or for identifying active regions of the genome in the zebrafish.

PMID- 9560251
TI  - A genetic system based on split-ubiquitin for the analysis of interactions
      between membrane proteins in vivo.
AB  - A detection system for interactions between membrane proteins in vivo is
      described. The system is based on split-ubiquitin [Johnsson, N. & Varshavsky, A.
      (1994) Proc. Natl. Acad. Sci. USA 91, 10340-10344]. Interaction between two
      membrane proteins is detected by proteolytic cleavage of a protein fusion. The
      cleavage releases a transcription factor, which activates reporter genes in the
      nucleus. As a result, interaction between membrane proteins can be analyzed by
      the means of a colorimetric assay. We use membrane proteins of the endoplasmic
      reticulum as a model system. Wbp1p and Ost1p are both subunits of the
      oligosaccharyl transferase membrane protein complex. The Alg5 protein also
      localizes to the membrane of the endoplasmic reticulum, but does not interact
      with the oligosaccharyltransferase. Specific interactions are detected between
      Wbp1p and Ost1p, but not between Wbp1p and Alg5p. The new system might be useful
      as a genetic and biochemical tool for the analysis of interactions between
      membrane proteins in vivo.

PMID- 9560252
TI  - Predicting amino acid sequences of the antibody human VH chains from its first
      several residues.
AB  - A new method for classification of Ig sequences is suggested. The defining
      characteristic of a class is presence of particular residues at several class
      determining positions. Sequences within a class follow the same amino acid
      pattern, i.e., residues at identical positions are, in an overwhelming majority
      of sequences of that class, identical or chemically related. Thus, once the class
      of a sequence is determined, one can predict the residue(s) at almost any
      position in the sequence. In this paper, results of analysis of 1,172 human heavy
      chains are presented. It was shown that a sequence can be assigned to one of six
      classes depending on which residues are found at its positions 1, 3, 5, 6, 7, 9,
      10, 12, and 13. It is important to note that it is possible to achieve same six
      class classification of the human heavy chains on the basis of a different set of
      positions found not at the beginning but near the end of the sequence (around
      position 80). For every class, an amino acid pattern of an entire sequence
      (complementarity determining regions excepting) has been determined. Our approach
      allowed us to reconstruct the incomplete human heavy chains in which residues at
      certain positions at the beginning or end of the chain are known. We developed a
      software tool for analysis, classification, and prediction of residues in
      sequences of the Ig family.

PMID- 9560253
TI  - HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A.
AB  - We previously showed that the availability of a nonamer peptide derived from
      certain HLA class I signal sequences is a necessary requirement for the
      stabilization of endogenous HLA-E expression on the surface of 721.221 cells.
      This led us to examine the ability of HLA-E to protect HLA class I transfectants
      from natural killer (NK) cell-mediated lysis. It was possible to implicate the
      CD94/NKG2A complex as an inhibitory receptor recognizing this class Ib molecule
      by using as target a .221 transfectant selectively expressing surface HLA-E. HLA
      E had no apparent inhibitory effect mediated through the identified Ig
      superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1. Further
      studies of CD94/NKG2+ NK cell-mediated recognition of .221 cells transfected with
      different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) confirmed that the
      inhibitory interaction was mediated by CD94/NKG2A recognizing the surface HLA-E
      molecule, because only antibodies directed against either HLA-E, CD94, or
      CD94/NKG2A specifically restored lysis. Surface stabilization of HLA-E in cold
      treated .221 cells loaded with appropriate peptides was sufficient to confer
      protection, resulting from recognition of the HLA class Ib molecule by the
      CD94/NKG2A inhibitory receptor. Consistent with the prediction that the ligand
      for CD94/NKG2A is expressed ubiquitously, our examination of HLA-E antigen
      distribution indicated that it is detectable on the surface of a wide variety of
      cell types.

PMID- 9560254
TI  - CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive beta
      chemokines.
AB  - beta-chemokines play an important role in the development of immunologic
      reactions. Macrophages are major beta-chemokine-producing cells during T-cell
      directed, delayed-type hypersensitivity reactions in tissues, and have been
      reported to be important producers of beta-chemokines in the lymph nodes of HIV-1
      infected individuals. However, the physiological signals responsible for inducing
      macrophages to produce beta-chemokines have not been established. Two soluble T
      cell products, interferon-gamma and granulocyte-macrophage colony stimulating
      factor, were added to cultured macrophages, but failed to stimulate the
      production of macrophage inflammatory protein-1alpha and -1beta; regulated upon
      activation, normal T cell expressed and secreted (RANTES); or monocyte
      chemoattractant protein-1. Instead, direct cell-cell contact between macrophages
      and cells engineered to express CD40L (also known as CD154) resulted in the
      production of large amounts of macrophage inflammatory protein-1alpha and -1beta,
      and RANTES (all ligands for CCR5), and monocyte chemoattractant protein-1 (a
      ligand for CCR2). Supernatants from CD40L-stimulated macrophages protected CD4(+)
      T cells from infection by a nonsyncytium-inducing strain of HIV-1 (which uses
      CCR5 as a coreceptor). These results have implications for granulomatous
      diseases, and conditions such as atherosclerosis and multiple sclerosis, where
      CD40L-bearing cells have been found in the macrophage-rich lesions where beta
      chemokines are being produced. Overall, these findings define a pathway linking
      the specific recognition of antigen by T cells to the production of beta
      chemokines by macrophages. This pathway may play a role in anti-HIV-1 immunity
      and the development of immunologic reactions or lesions.

PMID- 9560255
TI  - Identification of a meiosis-specific protein as a member of the class of
      cancer/testis antigens.
AB  - Little is known about the function of human cancer/testis antigens (CTAs), such
      as MAGE, BAGE, GAGE, HOM-MEL-40, and NY-ESO-1, the expression of which is
      restricted to human malignancies and testis. When screening a cDNA expression
      library enriched for testis-specific representative long transcripts for
      reactivity with high-titered IgG antibodies from the serum of a patient with
      renal cell carcinoma, one repeatedly detected antigen, designated HOM-TES-14,
      turned out to be encoded by the synaptonemal complex protein 1 (SCP-1) gene. SCP
      1 is known to be selectively expressed during the meiotic prophase of
      spermatocytes and is involved in the pairing of homologous chromosomes, an
      essential step for the generation of haploid cells in meiosis I. Investigation of
      a broad spectrum of normal and malignant tissues revealed expression of SCP-1
      transcripts and antigen selectively in a variety of neoplastic tissues and tumor
      cell lines. Immunofluorescence microscopy analysis with specific antiserum showed
      a cell cycle phase-independent nuclear expression of SCP-1 protein in cancer
      cells. SCP-1 differs from other members of the class of CTA by its localization
      on chromosome 1 and its frequent expression in malignant gliomas, breast, renal
      cell, and ovarian cancer. The aberrant expression of SCP-1 in tumors might
      contribute to their genomic instability and suggests that the functional role of
      other CTA might also relate to meiosis.

PMID- 9560256
TI  - On defining the rules for interactions between the T cell receptor and its
      ligand: a critical role for a specific amino acid residue of the T cell receptor
      beta chain.
AB  - The specificity of T cell-mediated immune responses is primarily determined by
      the interaction between the T cell receptor (TCR) and the antigenic peptide
      presented by the major histocompatibility complex (MHC) molecules. To refine our
      understanding of interactions between the TCR and the antigenic peptide of
      vesicular stomatitis virus (VSV) presented by the class I MHC molecule H-2Kb, we
      constructed a TCR alpha chain transgenic mouse in a TCR alpha-deficient
      background to define specific structural features in the TCR beta chain that are
      important for the recognition of the VSV/H-2Kb complex. We found that for a given
      peptide, a peptide-specific, highly conserved amino acid could always be
      identified at position 98 of the complementarity-determining region 3 (CDR3) loop
      of TCR beta chains. Further, we demonstrated that substitutions at position 6,
      but not position 1, of the VSV peptide induced compensatory changes in the TCR in
      both the amino acid residue at position 98 and the length of the CDR3beta loop.
      We conclude that the amino acid residue at position 98 of the CDR3beta loop is a
      key residue that plays a critical role in determining the specificity of TCR
      VSV/H-2Kb interactions and that a specific length of the CDR3beta loop is
      required to facilitate such interactions. Further, these findings suggest that
      the alpha and beta chains of TCRs interact with amino acid residue(s) toward the
      N and C termini of the VSV peptide, respectively, providing functional evidence
      for the orientation of a TCR with its peptide/MHC ligand as observed in the
      crystal structures of TCR/peptide/MHC complexes.

PMID- 9560257
TI  - Generation of CD8 suppressor factor and beta chemokines, induced by xenogeneic
      immunization, in the prevention of simian immunodeficiency virus infection in
      macaques.
AB  - Previous xenogeneic immunization experiments in rhesus macaques with simian
      immunodeficiency virus (SIV) grown in human CD4(+) T cells consistently elicited
      protection from challenge with live SIV. However, the mechanism of protection has
      not been established. We present evidence that xenogeneic immunization induced
      significant CD8 suppressor factor, RANTES (regulated upon activation, normal T
      cell expressed and secreted), macrophage inflammatory protein (MIP) 1alpha, and
      MIP-1beta (P < 0.001 - P < 0.02). The concentrations of these increased
      significantly in protected as compared with infected macaques (P < 0.001).
      Xenogeneic stimulation in vitro also up-regulated CD8 suppressor factors (SF; P <
      0.001) and the beta chemokines which were neutralized by antibodies to the 3 beta
      chemokines. Recombinant human RANTES, MIP-1alpha and MIP-1beta which bind to
      simian CCR5, suppressed SIV replication in a dose-dependent manner, with RANTES
      being more effective than the other two chemokines. The results suggest that
      immunization with SIV grown in human CD4(+) T cells induces CD8-suppressor
      factor, RANTES, MIP-1alpha and MIP-1beta which may block CCR5 receptors and
      prevent the virus from binding and fusion to CD4(+) cells.

PMID- 9560258
TI  - Bacteria-induced neo-biosynthesis, stabilization, and surface expression of
      functional class I molecules in mouse dendritic cells.
AB  - Here, we show that bacteria induce de novo synthesis of both major
      histocompatability complex (MHC) class I and II molecules in a mouse dendritic
      cell culture system. The neo-biosynthesis of MHC class I molecules is delayed as
      compared with that of MHC class II. Furthermore, bacteria stabilize MHC class I
      molecules by a 3-fold increase of their half-life. This has important
      consequences for the capacity of dendritic cells to present bacterial antigens in
      the draining lymph nodes. In addition, a model antigen, ovalbumin, expressed on
      the surface of recombinant Streptococcus gordonii is processed and presented on
      MHC class I molecules. This presentation is 10(6) times more efficient than that
      of soluble OVA protein. This exogenous pathway of MHC class I presentation is
      transporter associated with antigen processing (TAP)-dependent, indicating that
      there is a transport from phagolysosome to cytosol in dendritic cells. Thus,
      bacteria are shown to be a potentially useful mean for the correct delivery of
      exogenous antigens to be presented efficiently on MHC class I molecules.

PMID- 9560260
TI  - The CCR5 receptor acts as an alloantigen in CCR5Delta32 homozygous individuals:
      identification of chemokineand HIV-1-blocking human antibodies.
AB  - The chemokine receptor CCR5 is the major coreceptor for infection by macrophage
      tropic R5 HIV-1. A 32-bp deletion in the gene coding for CCR5 (CCR5Delta32)
      occurs with a frequency of 10% in the Caucasian population and results in a
      receptor protein that is truncated and not expressed at the cell surface.
      CCR5Delta32 homozygous individuals are apparently normal but resistant to
      infection with R5 HIV-1. In two individuals homozygous for CCR5Delta32, who had
      been repeatedly exposed to CCR5-expressing blood cells through sexual activity,
      we have identified antibodies to CCR5 that bound specifically to the surface of
      CCR5-expressing cell lines. Serum from these individuals, in contrast to serum
      from CCR5(+/+) individuals, competed with radiolabeled RANTES for binding to the
      CCR5 receptor and inhibited infection of peripheral blood mononuclear cells with
      R5, but not X4, primary isolates of HIV-1. The identified human antibodies to
      CCR5 define an alloantigen that may cause allograft rejection in a mismatch
      situation even in individuals with no history of blood transfusions or i.v. drug
      abuse.

PMID- 9560259
TI  - Differences in the level of expression of class I major histocompatibility
      complex proteins on thymic epithelial and dendritic cells influence the decision
      of immature thymocytes between positive and negative selection.
AB  - Both positive and negative selection of immature T cells rely on engagement of
      their antigen-specific receptors (TCR) by peptide in association with proteins
      encoded in the major histocompatibility complex (MHC) protein. The decision made
      between these two outcomes seems to be determined by the number of TCR engaged by
      peptide-MHC complexes. It has been unclear how such a mechanism can be reconciled
      with evidence that positive and negative selection occur in different thymic
      compartments and are mediated by different antigen-presenting cells (APCs). In
      this study we demonstrate that the level of class I MHC protein is 10-fold higher
      on thymic dendritic cells, which mediate the negative selection of immature T
      cells, than on thymic epithelial cells, which mediate for positive selection. We
      also demonstrate that as little as a 3-fold increase in the level of a particular
      cognate peptide-MHC ligand is sufficient to result in negative rather than
      positive selection. The results suggest that quantitative differences in the
      level of expression of class I MHC proteins on thymic epithelial and dendritic
      cells contribute to the opposing roles these cells play in forming the repertoire
      of mature class I MHC restricted (CD8+) T cells.

PMID- 9560261
TI  - Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer
      through loss of expression.
AB  - The recently identified PTEN/MMAC1 gene is a candidate tumor suppressor
      implicated in multiple tumor types based on mutations or homozygous deletions of
      the gene in certain human cancers. No studies of PTEN/MMAC1 mRNA or protein
      expression in cancer cells have been reported, primarily because of significant
      numbers of normal cells contaminating most tumor samples and because of the lack
      of antibody reagents. We examined PTEN/MMAC1 in advanced prostate cancer for gene
      mutations or abnormalities in expression by using a series of recently derived
      xenografts free of normal human cells and a PTEN/MMAC1-specific antibody. Only 1
      of 10 tumors contained a homozygous deletion of PTEN/MMAC1, and no mutations were
      detected in the entire coding region of the remaining nine xenografts. However,
      five of these showed reduced or absent PTEN/MMAC1 expression by Northern analysis
      and reverse transcription-PCR of mRNA. PTEN/MMAC1 mRNA expression was restored in
      nonexpressing prostate cancer cells by in vitro treatment with the demethylating
      agent 5-azadeoxycytidine. Alterations in PTEN/MMAC1 expression were confirmed at
      the protein level by immunoblot analysis, and immunohistochemical studies show
      that the endogenous wild-type PTEN/MMAC1 protein is localized exclusively in the
      cytoplasm. These results demonstrate that loss of PTEN/MMAC1 expression occurs
      frequently in advanced prostate cancer.

PMID- 9560262
TI  - Modulation of ventricular function through gene transfer in vivo.
AB  - We used a catheter-based technique to achieve generalized cardiac gene transfer
      in vivo and to alter cardiac function by overexpressing phospholamban (PL) which
      regulates the activity of the sarcoplasmic reticulum Ca2+ ATPase (SERCA2a). By
      using this approach, rat hearts were transduced in vivo with 5 x 10(9) pfu of
      recombinant adenoviral vectors carrying cDNA for either PL, beta-galactosidase
      (beta-gal), or modified green fluorescent protein (EGFP). Western blot analysis
      of ventricles obtained from rats transduced by Ad.PL showed a 2.8-fold increase
      in PL compared with hearts transduced by Ad.betagal. Two days after infection,
      rat hearts transduced with Ad.PL had lower peak left ventricular pressure (58.3
      +/- 12.9 mmHg, n = 8) compared with uninfected hearts (92.5 +/- 3.5 mmHg, n = 6)
      or hearts infected with Ad.betagal (92.6 +/- 5.9 mmHg, n = 6). Both peak rate of
      pressure rise and pressure fall (+3, 210 +/- 298 mmHg/s, -2, 117 +/- 178 mmHg/s,
      n = 8) were decreased in hearts overexpressing PL compared with uninfected hearts
      (+5, 225 +/- 136 mmHg/s, -3, 805 +/- 97 mmHg/s, n = 6) or hearts infected with
      Ad.betagal (+5, 108 +/- 167 mmHg/s, -3, 765 +/- 121 mmHg/s, n = 6). The time
      constant of left ventricular relaxation increased significantly in hearts
      overexpressing PL (33.4 +/- 3.2 ms, n = 8) compared with uninfected hearts (18.5
      +/- 1.0 ms, n = 6) or hearts infected with Ad.betagal (20.8 +/- 2.1 ms, n = 6).
      These differences in ventricular function were maintained 7 days after infection.
      These studies open the prospect of using somatic gene transfer to modulate
      overall cardiac function in vivo for either experimental or therapeutic
      applications.

PMID- 9560263
TI  - Autologously up-regulated Fc receptor expression and action in airway smooth
      muscle mediates its altered responsiveness in the atopic asthmatic sensitized
      state.
AB  - To elucidate the role of IgE-dependent mechanisms in inducing altered airway
      responsiveness in the atopic asthmatic state, the expression and actions of Fc
      receptor activation were examined in isolated rabbit tracheal smooth muscle (TSM)
      tissue and cultured cells passively sensitized with sera from atopic asthmatic
      patients or nonatopic/nonasthmatic (control) subjects. Relative to control
      tissues, the atopic asthmatic-sensitized TSM exhibited significantly increased
      maximal isometric contractility to acetylcholine (P < 0. 01) and attenuated
      maximal relaxation responses and sensitivity (i.e.,-log ED50) to isoproterenol (P
      < 0.005). These changes in agonist responsiveness in atopic sensitized TSM were
      ablated by pretreating the tissues with a blocking mAb to the low affinity
      receptor for IgE, FcepsilonRII (i.e., CD23) or by depleting the sensitizing serum
      of its immune complexes. Moreover, in complimentary experiments, exogenous
      administration of IgE immune complexes to naive TSM produced changes in agonist
      responsiveness that were qualitatively similar to those obtained in the atopic
      asthmatic-sensitized state. Extended studies further demonstrated that, in
      contrast to their respective controls, atopic asthmatic serum-sensitized human
      and rabbit TSM tissue and cultured cells exhibited markedly induced mRNA and cell
      surface expression of FcepsilonRII, whereas constitutive expression of the IgG
      receptor subtype, FcgammaRIII, was unaltered. Finally, the up-regulated mRNA
      expression of FcepsilonRII observed following exposure of TSM to atopic asthmatic
      serum or to exogenously administered IgE immune complexes was significantly
      inhibited by pretreating the tissues or cells with anti-CD23 mAb. Collectively,
      these observations provide evidence demonstrating that the altered agonist
      responsiveness in atopic asthmatic sensitized airway smooth muscle is largely
      attributed to IgE-mediated induction of the autologous expression and activation
      of FcepsilonRII receptors in the airway smooth muscle itself.

PMID- 9560264
TI  - Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion
      injury.
AB  - Reperfusion injury, which occurs upon the reintroduction of blood flow to an
      ischemic organ, is responsible for considerable damage in heart attacks and
      strokes. However, no treatment for reperfusion injury is currently available. A
      major cause of reperfusion injury is the iron-mediated generation of hydroxyl
      radical (.OH). In this study we have explored the capacity of novel iron
      chelators called "exochelins" to prevent reperfusion injury. Exochelins,
      siderophores of Mycobacterium tuberculosis, are unique iron chelators because
      they are lipid soluble, and hence able to enter cells rapidly. In the iron-free
      state, exochelins prevented .OH formation. Desferri-exochelins prevented
      oxidative injury to cultured cardiac myocytes, and did so more rapidly and
      effectively than the nonlipid soluble iron chelator deferoxamine. The capacity of
      various desferri-exochelins to protect myocytes from oxidative injury varied
      directly with their solubility in lipid. Infused into isolated rabbit hearts
      during reperfusion after a period of ischemia, desferri-exochelins dramatically
      improved systolic and diastolic left ventricular function, preserved coronary
      flow, reduced release of the cardiac enzyme lactic dehydrogenase, and reduced
      myocardial concentrations of .OH metabolites. Thus, highly diffusible desferri
      exochelins block injury caused by .OH production and have potential for the
      treatment of reperfusion injury.

PMID- 9560265
TI  - Targeted expression of a multifunctional chimeric neurotrophin in the lesioned
      sciatic nerve accelerates regeneration of sensory and motor axons.
AB  - Peripheral nerve injury markedly regulates expression of neurotrophins and their
      receptors in the lesioned nerve. However, the role of endogenously produced
      neurotrophins in the process of nerve regeneration is unclear. Expression of a
      multifunctional neurotrophin, pan-neurotrophin-1 (PNT-1), was targeted to the
      peripheral nerves of transgenic mice by using a gene promoter that is
      specifically activated after nerve lesion but that is otherwise silent in all
      other tissues and during development. PNT-1 is a chimeric neurotrophin that
      combines the active sites of the neurotrophins nerve growth factor, brain-derived
      neurotrophic factor, and neurotrophin-3 and binds and activates all known
      neurotrophin receptors. In adult transgenic mice, PNT-1 was highly expressed in
      transected but not in intact sciatic nerve. Morphometric analyses at the electron
      microscopy level showed increased and accelerated recovery of axon diameter of
      myelinated fibers in crushed peripheral nerves of transgenic mice compared with
      wild type. Examination of nerve bundles in target tissues indicated accelerated
      reinnervation of foot pad dermis and flexor plantaris muscle in transgenic mice.
      Moreover, transected sensory and motor axons of transgenic mice showed faster and
      increased return of neurophysiological responses, suggesting an accelerated rate
      of axonal elongation. Importantly, transgenic mice also showed a markedly
      ameliorated loss of skeletal muscle weight, indicating functional regeneration of
      motor axons. Together, these data provide evidence, at both the anatomical and
      functional levels, that neurotrophins endogenously produced by the lesioned nerve
      are capable of significantly accelerating the regeneration of both sensory and
      motor axons after peripheral nerve damage. In addition, our results indicate that
      exogenous PNT-1 administration may be an effective therapeutic treatment of
      peripheral nerve injuries.

PMID- 9560266
TI  - Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases.
AB  - The activity of chemical carcinogens is a complex balance between metabolic
      activation by cytochrome P450 monooxygenases and detoxification by enzymes such
      as glutathione S-transferase (GST). Regulation of these proteins may have
      profound effects on carcinogenic activity, although it has proved impossible to
      ascribe the observed effects to the activity of a single protein. GstP appears to
      play a very important role in carcinogenesis, although the precise nature of its
      involvement is unclear. We have deleted the murine GstP gene cluster and
      established the effects on skin tumorigenesis induced by the polycyclic aromatic
      hydrocarbon 7, 12-dimethylbenz anthracene and the tumor promoting agent 12-O
      tetradecanoylphorbol-13-acetate. After 20 weeks, a highly significant increase in
      the number of papillomas was found in the GstP1/P2 null mice [GstP1/P2(-/-) mice,
      179 papillomas, mean 9.94 per animal vs. GstP1/P2(+/+) mice, 55 papillomas, mean
      2.89 per animal, (P < 0.001)]. This difference in tumor incidence provides direct
      evidence that a single gene involved in drug metabolism can have a profound
      effect on tumorigenicity, and demonstrates that GstP may be an important
      determinant in cancer susceptibility, particularly in diseases where exposure to
      polycyclic aromatic hydrocarbons is involved, for instance in cigarette smoke
      induced lung cancer.

PMID- 9560267
TI  - HIV transcriptional activation by the accessory protein, VPR, is mediated by the
      p300 co-activator.
AB  - The accessory protein, Vpr, is a virion-associated protein that is required for
      HIV-1 replication in macrophages and regulates viral gene expression in T cells.
      Vpr causes arrest of cell cycle progression at G2/M, presumably through its
      effect on cyclin B1.Cdc2 activity. Here, we show that the ability of Vpr to
      activate HIV transcription correlates with its ability to induce G2/M growth
      arrest, and this effect is mediated by the p300 transcriptional co-activator,
      which promotes cooperative interactions between the Rel A subunit of NF-kappaB
      and cyclin B1.Cdc2. Vpr cooperates with p300, which regulates NF-kappaB and the
      basal transcriptional machinery, to increase HIV gene expression. Similar effects
      are seen in the absence of Vpr with a kinase-deficient Cdc2, and overexpression
      of p300 increases levels of HIV Vpr+ replication. Taken together, these data
      suggest that p300, through its interactions with NF-kappaB, basal transcriptional
      components, and Cdks, is modulated by Vpr and regulates HIV replication. The
      regulation of p300 by Vpr provides a mechanism to enhance viral replication in
      proliferating cells after growth arrest by increasing viral transcription.

PMID- 9560268
TI  - The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl
      methanesulfonate treatment.
AB  - The BRCA2 gene was identified based on its involvement in familial breast cancer.
      The analysis of its sequence predicts that the gene encodes a protein with 3,418
      amino acids but provides very few clues pointing to its biological function. In
      an attempt to address this question, specific antibodies were prepared that
      identified the gene product of BRCA2 as a 390-kDa nuclear protein. Furthermore,
      direct binding of human RAD51 to each of the four single 30-amino acid BRC
      repeats located at the 5' portion of exon 11 of BRCA2 was demonstrated. Such an
      interaction is significant, as BRCA2 and RAD51 can be reciprocally
      coimmunoprecipitated by each of the individual, specific antibodies and form
      complexes in vivo. Inferring from the function of RAD51 in DNA repair, human
      pancreatic cancer cells, Capan-1, expressing truncated BRCA2 were shown to be
      hypersensitive to methyl methanesulfonate (MMS) treatment. Exogenous expression
      of wild-type BRCA2, but not BRC-deleted mutants, in Capan-1 cells confers
      resistance to MMS treatment. These results suggest that the interaction between
      the BRC repeats of BRCA2 and RAD51 is critical for cellular response to DNA
      damage caused by MMS.

PMID- 9560269
TI  - Agrobacterium transcriptional regulator Ros is a prokaryotic zinc finger protein
      that regulates the plant oncogene ipt.
AB  - Virulence genes of Agrobacterium tumefaciens are under the control of positive
      and negative transcriptional regulators. We found that the transcriptional
      regulator Ros controls expression of the plant oncogene ipt, which encodes
      isopentenyl transferase, in A. tumefaciens. This enzyme is involved in
      biosynthesis of the plant growth hormone cytokinin in the host plant. An ipt
      promoter::cat reporter gene fusion showed a 10-fold increase in ipt promoter
      activity in A. tumefaciens ros mutant strains when compared with wild type. Also,
      increased levels (10- to 20-fold) of isopentenyl adenosine, the product of the
      reaction catalyzed by isopentenyl transferase, were detected in ros mutant
      strains. In vitro studies using purified Ros showed it binds directly to the ipt
      promoter. Analysis of the deduced Ros amino acid sequence identified a novel type
      of C2H2 zinc finger. In Ros the peptide loop spacing of the zinc finger is 9
      amino acids as opposed to the invariant 12 amino acids in the classical C2H2
      motif. Site-directed mutagenesis of Cys-82 and His-92 in this motif showed that
      these residues are essential for Zn2+ and DNA binding activities of Ros. The
      existence of such a regulator in Agrobacterium may be due to horizontal
      interkingdom retrotransfer of the ros gene from plant to bacteria.

PMID- 9560270
TI  - Mycobacterium bovis Bacille Calmette-Guerin strains secreting listeriolysin of
      Listeria monocytogenes.
AB  - Recombinant (r) Mycobacterium bovis strains were constructed that secrete
      biologically active listeriolysin (Hly) fusion protein of Listeria monocytogenes.
      The r-BCG strains pAT261:Hly or pMV306:Hly expressed plasmid multicopies or
      chromosomal single copies of the hly gene, respectively. Human and murine
      macrophage-like cell lines were infected with r-BCG pAT261:Hly and pMV306:Hly
      strains. Interestingly, intracellular persistence of both r-BCG strains was
      reduced in macrophages as compared with the parental BCG strain. By immunogold
      labeling Hly was detected in membrane structures and within the phagosomal space
      of macrophages. In addition, Hly was localized within cytoplasmic vacuoles
      outside the mycobacteria-containing phagosome of host cells infected with r-BCG
      pAT261:Hly or r-BCG pMV306:Hly. Hly fusions consistently colocalized with a
      lysosome-associated membrane glycoprotein, suggesting that membrane-attack
      conformation of Hly was not altered. Although r-BCG pAT261:Hly and r-BCG
      pMV306:Hly microorganims apparently did not egress into the cytoplasmic
      compartment of host cells, they both improved major histocompatibility complex
      class I presentation of cophagocytosed soluble protein as compared with wild-type
      BCG microbes. These data suggest that Hly secretion endows BCG with an improved
      capacity to stimulate CD8 T cells. Because CD8 T cells play a major role in
      protection against tuberculosis such Hly secreting r-BCG constructs are
      antituberculosis vaccine candidates.

PMID- 9560272
TI  - Down-regulation of Leishmania donovani trypanothione reductase by heterologous
      expression of a trans-dominant mutant homologue: effect on parasite intracellular
      survival.
AB  - A trans-dominant mutational strategy was used to down-regulate trypanothione
      reductase (TR) activity levels in Leishmania donovani, the causative agent of
      visceral leishmaniasis in humans. TR, regarded as an ideal drug target against
      trypanosomatid infections, is a homodimeric flavoprotein oxidoreductase unique to
      these organisms that plays a central role in the enzymatic regeneration of the
      thiol pool. Extrachromosomal, heterologous expression of a trans-dominant mutant
      version of the Trypanosoma cruzi enzyme in L. donovani resulted in the formation
      of inactive cross-species heterodimers and in a dramatic decrease of endogenous
      TR activity levels. Recombinant cells depleted of up to 85% of TR activity were
      significantly impaired in their ability to regenerate dihydrotrypanothione from
      trypanothione disulfide following oxidation with diamide. Nonetheless trans
      dominant mutant recombinants were still capable of maintaining a reduced
      intracellular environment during cell growth in culture and were able to
      metabolize hydrogen peroxide at wild-type rates in vitro. Importantly, however,
      cells expressing the trans-dominant mutant enzyme displayed a decreased ability
      to survive inside activated macrophages in a murine model of Leishmania
      infection. The apparent inability of Leishmania to modulate the expression of
      active TR homodimers in response to the expression of trans-dominant mutant
      protein suggests that specific inhibitors of this enzyme should be useful anti
      leishmanial agents.

PMID- 9560271
TI  - DNA strand separation during activation of a developmental promoter by the
      Bacillus subtilis response regulator Spo0A.
AB  - Spo0A is the central regulator of commitment to sporulation in Bacillus subtilis.
      Spo0A is a member of the response regulator family of proteins and both represses
      and stimulates transcription from promoters when activated. In vivo Spo0A
      activation takes place by phosphorylation and in vitro activation can be
      accomplished by phosphorylation or removal of the N-terminal domain of the
      protein. We have examined the mechanism of Spo0A stimulation of transcription
      from the promoter of the spoIIG operon. This operon encodes one of the first
      compartment specific sigma factors whose appearance regulates sporulation
      development. When activated Spo0A was incubated with RNA polymerase and a DNA
      fragment containing the spoIIG promoter, bases between -13 and -3, relative to
      the start site of transcription, were denatured. Addition of activated Spo0A or
      RNA polymerase alone did not induce denaturation. Heteroduplex templates that
      contained the nontemplate sequence of the wild-type promoter on both strands
      between positions -3 and -13 were efficiently transcribed without activated
      Spo0A. These data suggest that DNA strand separation is a two-step process and
      that the activation of Spo0A creates a form that interacts with the polymerase to
      induce the first of the two steps.

PMID- 9560273
TI  - Antibacterial agents that inhibit two-component signal transduction systems.
AB  - A class of antibacterials has been discovered that inhibits the growth of Gram
      positive pathogenic bacteria. RWJ-49815, a representative of a family of
      hydrophobic tyramines, in addition to being a potent bactericidal Gram-positive
      antibacterial, inhibits the autophosphorylation of kinase A of the KinA::Spo0F
      two-component signal transduction system in vitro. Analogs of RWJ-49815 vary
      greatly in their ability to inhibit growth of bacteria and this ability
      correlates directly with their activity as kinase A inhibitors. Compared with the
      potent quinolone, ciprofloxacin, RWJ-49815 exhibits reduced resistance emergence
      in a laboratory passage experiment. Inhibition of the histidine protein
      kinase::response regulator two-component signal transduction pathways may present
      an opportunity to depress chromosomal resistance emergence by targeting multiple
      proteins with a single inhibitor in a single bacterium. Such inhibitors may
      represent a class of antibacterials that potentially may represent a breakthrough
      in antibacterial therapy.

PMID- 9560274
TI  - Differential signaling via the same axon of neocortical pyramidal neurons.
AB  - The nature of information stemming from a single neuron and conveyed
      simultaneously to several hundred target neurons is not known. Triple and
      quadruple neuron recordings revealed that each synaptic connection established by
      neocortical pyramidal neurons is potentially unique. Specifically, synaptic
      connections onto the same morphological class differed in the numbers and
      dendritic locations of synaptic contacts, their absolute synaptic strengths, as
      well as their rates of synaptic depression and recovery from depression. The same
      axon of a pyramidal neuron innervating another pyramidal neuron and an
      interneuron mediated frequency-dependent depression and facilitation,
      respectively, during high frequency discharges of presynaptic action potentials,
      suggesting that the different natures of the target neurons underlie qualitative
      differences in synaptic properties. Facilitating-type synaptic connections
      established by three pyramidal neurons of the same class onto a single
      interneuron, were all qualitatively similar with a combination of facilitation
      and depression mechanisms. The time courses of facilitation and depression,
      however, differed for these convergent connections, suggesting that different pre
      postsynaptic interactions underlie quantitative differences in synaptic
      properties. Mathematical analysis of the transfer functions of frequency
      dependent synapses revealed supra-linear, linear, and sub-linear signaling
      regimes in which mixtures of presynaptic rates, integrals of rates, and
      derivatives of rates are transferred to targets depending on the precise values
      of the synaptic parameters and the history of presynaptic action potential
      activity. Heterogeneity of synaptic transfer functions therefore allows multiple
      synaptic representations of the same presynaptic action potential train and
      suggests that these synaptic representations are regulated in a complex manner.
      It is therefore proposed that differential signaling is a key mechanism in
      neocortical information processing, which can be regulated by selective synaptic
      modifications.

PMID- 9560275
TI  - Regulation of thalamic neurite outgrowth by the Eph ligand ephrin-A5:
      implications in the development of thalamocortical projections.
AB  - The cerebral cortex is parcellated into different functional domains that receive
      distinct inputs from other cortical and subcortical regions. The molecular
      mechanisms underlying the specificity of connections of cortical afferents remain
      unclear. We report here that the Eph family tyrosine kinase receptor EphA5 and
      the ligand ephrin-A5 may play a key role in the exclusion of the limbic thalamic
      afferents from the sensorimotor cortex by mediating repulsive interactions. In
      situ hybridization shows that the EphA5 transcript is expressed at high levels in
      both cortical and subcortical limbic regions, including the frontal cortex, the
      subiculum, and the medial thalamic nuclei. In contrast, ephrin-A5 is transcribed
      abundantly in the sensorimotor cortex. Consistent with the complementary
      expression, the ligand inhibited dramatically the growth of neurites from neurons
      isolated from the medial thalamus but was permissive for the growth of neurites
      from lateral thalamic neurons, which is primarily nonlimbic. Similarly, the
      growth of neurites from Eph-A5-expressing neurons isolated from the subiculum was
      inhibited by ephrin-A5. Our studies suggest that the Eph family ligand ephrin-A5
      serves as a general inhibitor of axonal growth from limbic neurons, which may
      serve to prevent innervation of inappropriate primary sensorimotor regions, thus
      contributing to the generation of specificity of thalamic cortical afferents.

PMID- 9560276
TI  - Maternal care during infancy regulates the development of neural systems
      mediating the expression of fearfulness in the rat.
AB  - The mothers of infant rats show individual differences in the frequency of
      licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the
      development of individual differences in behavioral responses to stress. As
      adults, the offspring of mothers that exhibited high levels of LG-ABN showed
      substantially reduced behavioral fearfulness in response to novelty compared with
      the offspring of low LG-ABN mothers. In addition, the adult offspring of the high
      LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor
      density in the central, lateral, and basolateral nuclei of the amygdala as well
      as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the
      locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH)
      receptor density in the locus ceruleus. The expression of fear and anxiety is
      regulated by a neural circuitry that includes the activation of ascending
      noradrenergic projections from the locus ceruleus to the forebrain structures.
      Considering the importance of the amygdala, notably the anxiogenic influence of
      CRH projections from the amygdala to the locus ceruleus, as well as the
      anxiolytic actions of benzodiazepines, for the expression of behavioral responses
      to stress, these findings suggest that maternal care during infancy serves to
      "program" behavioral responses to stress in the offspring by altering the
      development of the neural systems that mediate fearfulness.

PMID- 9560278
TI  - Reinnervation of cross-regenerated gustatory nerve fibers into amiloride
      sensitive and amiloride-insensitive taste receptor cells.
AB  - Single nerve fiber responses to NaCl and their inhibition by amiloride were
      compared among the chorda tympani (CT) and glossopharyngeal (IXth), and their
      cross-regenerated nerves in the C57BL/KsJ mice. The CT nerve innervating the
      anterior part of the tongue contained approximately equal numbers of two types of
      NaCl-responsive neurons; one type showed strong suppression of NaCl responses by
      amiloride [amiloride-sensitive (AS) type], and the other type showed only weak or
      no suppression of NaCl responses by amiloride [amiloride-insensitive (AI) type].
      In contrast, the IXth nerve innervating the posterior part of the tongue has
      almost exclusively the AI type. This relative abundance of the AS and AI types of
      fibers was not altered by cross-regeneration of the two gustatory nerves into the
      reverse tongue regions. This suggests that regenerated taste axons selectively
      recouple with the appropriate type of receptor cell whether they innervate the
      front or the back of the tongue. Such selective synapse reformation may help
      explain the stability of response profiles of taste neurons during continual
      receptor cell turnover.

PMID- 9560277
TI  - A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively
      altered in schizophrenia.
AB  - In the primate cerebral cortex, morphologically and functionally diverse classes
      of local circuit neurons containing the inhibitory neurotransmitter gamma
      aminobutyric acid (GABA) differentially regulate the activity of pyramidal cells,
      the principal type of excitatory output neurons. In schizophrenia, GABA
      neurotransmission in the prefrontal cortex (PFC) appears to be disturbed but
      whether specific populations of GABA neurons are affected is not known. The
      chandelier class of GABA neurons are of particular interest because their axon
      terminals, which form distinctive arrays termed "cartridges," provide inhibitory
      input exclusively to the axon initial segment of pyramidal cells. Thus,
      chandelier cells are positioned to powerfully regulate the excitatory output of
      pyramidal neurons and, consequently, to substantially affect the patterns of
      neuronal activity within the PFC. In this study, an antibody directed against the
      GABA membrane transporter GAT-1 was used to label GABA axon terminals in
      postmortem human brains. The relative density of GAT-1-immunoreactive axon
      cartridges furnished by chandelier neurons was decreased by 40% in the PFC of
      schizophrenic subjects compared with matched groups of normal control and
      nonschizophrenic psychiatric subjects. In contrast, markers of the axon terminals
      of other populations of GABA neurons were not altered in the schizophrenic
      subjects. Furthermore, the density of GAT-1-immunoreactive axon cartridges was
      not altered in psychiatric subjects who had been treated with antipsychotic
      medications. The changes in GAT-1-immunoreactive axon cartridges of chandelier
      neurons in schizophrenia are likely to reflect altered information processing
      within the PFC and in its output connections to other brain regions and could
      contribute to the cognitive impairments seen in this disorder.

PMID- 9560279
TI  - High expression levels in cones of RGS9, the predominant GTPase accelerating
      protein of rods.
AB  - RGS9 is a member of the RGS family of GTPase accelerating proteins (GAPs) for
      heterotrimeric G proteins. We have explored its contribution to GTPase
      acceleration in mammalian rod and cone photoreceptors. When RGS9 was specifically
      removed from detergent extracts of rod outer segments by immunodepletion, the
      extracts lost nearly all of their GAP activity stimulatable by the inhibitory
      subunit of cGMP phosphodiesterase. Immunolocalization using monoclonal antibodies
      and confocal microscopy revealed that RGS9 is present in cones at significantly
      higher levels than in rods. Thus, RGS9 is the predominant source of GAP activity
      in rod outer segments, and RGS9 concentration emerges as a potentially important
      determinant of the faster response kinetics and lower sensitivity of mammalian
      cones, as compared with rods.

PMID- 9560280
TI  - Effect of intravenous infusions of 12-O-tetradecanoylphorbol-13-acetate (TPA) in
      patients with myelocytic leukemia: preliminary studies on therapeutic efficacy
      and toxicity.
AB  - Studies by several investigators have shown that 12-0-tetradecanoylphorbol-13
      acetate (TPA) is an extraordinarily potent stimulator of differentiation of
      cultured human promyelocytic leukemia cells in vitro. In the present study, TPA
      was administered to humans by i.v. infusion without irreversible toxicity, and it
      was shown to have pharmacological activity for the treatment of myelocytic
      leukemia in patients refractory to cytosine arabinoside (Ara C), retinoic acid,
      and other antileukemic drugs. Marked decreases in bone marrow myeloblasts as well
      as temporary remission of disease symptoms were observed when TPA was
      administered alone or in combination with vitamin D3 and Ara C. Additional
      studies with TPA after the determination of optimum dosing regimens are needed to
      determine whether long-lasting or permanent remissions of myelocytic leukemia can
      be achieved. Transient and reversible side effects were observed after a 1-mg
      i.v. dose of TPA, but these adverse effects became less intense or disappeared
      when a lower dose of TPA was used. The results of this study indicate a
      therapeutic effect of TPA in patients with myelocytic leukemia.

PMID- 9560281
TI  - 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced increase in depressed white
      blood cell counts in patients treated with cytotoxic cancer chemotherapeutic
      drugs.
AB  - Fifty-two patients with solid tumors had depressed white blood cell and
      neutrophil counts because of prior treatment with cytotoxic cancer
      chemotherapeutic drugs. These patients were given one or more i.v. infusions of
      0.125-0.25 mg of 12-O-tetradecanoylphorbol-13-acetate (TPA), and this treatment
      increased the low white blood cell and neutrophil counts toward the normal range.
      The average white blood cell and neutrophil counts were 2.55 x 10(9)/liter and
      1.76 x 10(9)/liter, respectively, before treatment with TPA. After one or more
      i.v. infusions of TPA, the white blood cell and neutrophil counts increased to
      peak values of 5. 92 x 10(9)/liter and 4.76 x 10(9)/liter, respectively, within a
      few days. Most patients had increased levels of white blood cells and neutrophils
      by 24 hr after a single i.v. infusion of 0.25 mg TPA. Elevated levels were
      observed for at least 3 days. This study demonstrates that treatment with
      parenteral TPA is feasible with useful biological activity. Only mild and
      reversible side effects were observed.

PMID- 9560282
TI  - Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer
      cell lines.
AB  - Nerve growth factor (NGF) has antiproliferative and differentiating effects on
      adenomas of neuroendocrine origin. Cell lines derived from small-cell lung
      carcinoma (SCLC), a very aggressive neuroendocrine tumor, express NGF receptors.
      The role of NGF in the control of proliferation and progression of this
      carcinoma, however, has never been investigated. Chronic exposure of NCI-N-592
      and GLC8 SCLC cell lines to NGF remarkably inhibited their proliferation rate
      both in vitro and in vivo, prevented their anchorage-independent clonal growth in
      soft agar, impaired their invasive capacity in vitro, and abolished their
      tumorigenic potential in nude mice. The proliferative response of SCLC cell lines
      to nicotine was also remarkably impaired by in vitro NGF treatment. Furthermore,
      NGF treatment activates in SCLC cell lines the expression and secretion of NGF.
      NGF thus reverts SCLC cell lines to a noninvasive, nontumorigenic phenotype that
      does not respond to nicotine and produces NGF.

PMID- 9560284
TI  - Migrating transformed MDCK cells are able to structurally polarize a voltage
      activated K+ channel.
AB  - Cell migration of transformed renal epithelial cells (MDCK-F) depends-in addition
      to cytoskeletal mechanisms-on the polarized activity of a Ca2+-sensitive K+
      channel in the rear part of the cells. However, because of the lack of specific
      markers for this channel we are not able to determine whether a polarized
      distribution of the channel protein underlies its functional polarization. To
      determine whether the migrating MDCK-F cells have retained the ability to target
      K+ channels to distinct membrane areas we stably transfected the cells with the
      voltage-dependent K+ channel Kv1.4. Stable expression and insertion into the
      plasma membrane could be shown by reverse transcription-PCR, genomic PCR, Western
      blot, and patch-clamp techniques, respectively. The distribution of Kv1.4 was
      assessed with indirect immunofluorescence by using conventional and confocal
      microscopy. These experiments revealed that Kv1.4 is expressed only in
      transfected cells where it elicits the typical voltage-dependent, rapidly
      inactivating K+ current. The Kv1.4 protein is clustered at the leading edge of
      protruding lamellipodia of migrating MDCK-F cells. This characteristic
      distribution of Kv1.4 provides strong evidence that migrating MDCK-F cells are
      able to insert ion channels into the plasma membrane in an asymmetric way, which
      reflects the polarization of migrating cells in the plane of movement. These
      findings suggest that not only epithelial cells and nerve cells, but also
      migrating cells, can create functionally distinct plasma membrane areas.

PMID- 9560283
TI  - Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting,
      hypercalciuria, and skeletal abnormalities.
AB  - Npt2 encodes a renal-specific, brush-border membrane Na+-phosphate (Pi)
      cotransporter that is expressed in the proximal tubule where the bulk of filtered
      Pi is reabsorbed. Mice deficient in the Npt2 gene were generated by targeted
      mutagenesis to define the role of Npt2 in the overall maintenance of Pi
      homeostasis, determine its impact on skeletal development, and clarify its
      relationship to autosomal disorders of renal Pi reabsorption in humans.
      Homozygous mutants (Npt2(-/-)) exhibit increased urinary Pi excretion,
      hypophosphatemia, an appropriate elevation in the serum concentration of 1,25
      dihydroxyvitamin D with attendant hypercalcemia, hypercalciuria and decreased
      serum parathyroid hormone levels, and increased serum alkaline phosphatase
      activity. These biochemical features are typical of patients with hereditary
      hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian disorder of
      renal Pi reabsorption. However, unlike HHRH patients, Npt2(-/-) mice do not have
      rickets or osteomalacia. At weaning, Npt2(-/-) mice have poorly developed
      trabecular bone and retarded secondary ossification, but, with increasing age,
      there is a dramatic reversal and eventual overcompensation of the skeletal
      phenotype. Our findings demonstrate that Npt2 is a major regulator of Pi
      homeostasis and necessary for normal skeletal development.

PMID- 9560285
TI  - Phosphorylation of a twitchin-related protein controls catch and calcium
      sensitivity of force production in invertebrate smooth muscle.
AB  - "Catch" is a condition of prolonged, high-force maintenance at resting
      intracellular Ca2+ concentration ([Ca2+]) and very low energy usage, occurring in
      invertebrate smooth muscles, including the anterior byssus retractor muscle
      (ABRM) of Mytilus edulis. Relaxation from catch is rapid on serotonergic nerve
      stimulation in intact muscles and application of cAMP in permeabilized muscles.
      This release of catch occurs by protein kinase A-mediated phosphorylation of a
      high (approximately 600 kDa) molecular mass protein, the regulator of catch.
      Here, we identify the catch-regulating protein as a homologue of the mini-titin,
      twitchin, based on (i) a partial cDNA of the purified isolated protein showing
      77% amino acid sequence identity to the kinase domain of Aplysia californica
      twitchin; (ii) a polyclonal antibody to a synthetic peptide in this sequence
      reacting with the phosphorylated catch-regulating protein band from permeabilized
      ABRM; and (iii) the similarity of the amino acid composition and molecular weight
      of the protein to twitchin. In permeabilized ABRM, at all but maximum [Ca2+],
      phosphorylation of twitchin results in a decreased calcium sensitivity of force
      production (half-maximum at 2.5 vs. 1.3 microM calcium). At a given submaximal
      force, with equal numbers of force generators, twitchin phosphorylation increased
      unloaded shortening velocity approximately 2-fold. These data suggest that
      aspects of the catch state exist not only at resting [Ca2+], but also at higher
      submaximal [Ca2+]. The mechanism that gives rise to force maintenance in catch
      probably operates together, to some extent, with that of cycling myosin
      crossbridges.

PMID- 9560286
TI  - Expression of the Na+/Ca2+ exchanger emerges in hepatic stellate cells after
      activation in association with liver fibrosis.
AB  - Activation of hepatic stellate (Ito) cells is a final common pathway of liver
      fibrosis. The findings presented in this paper indicate that expression of
      Na+/Ca2+ exchanger (NCX) emerges in rat hepatic stellate cells after activation
      in vitro during primary culture or in vivo in response to intoxication with CCl4.
      NCX mRNA became detectable by Northern blot analysis in cultured stellate cells
      on day 3, as was alpha-smooth muscle actin, an indicator not only of smooth
      muscle differentiation but also of stellate cell activation. Western blot
      analysis showed expression of the exchanger protein in the activated stellate
      cells. Functional expression of the exchanger, monitored by Ni2+-sensitive,
      verapamil-insensitive intracellular free Ca2+ increases in response to reduction
      of extracellular Na+ concentration, became sizable by using Fura-2 in stellate
      cells by 7 days in culture. Furthermore, increased expression of the exchanger
      mRNA was found predominantly in stellate cells freshly isolated from the CCl4
      model rat of hepatic fibrosis. Thus, it is concluded that NCX expression is
      closely associated with activation of hepatic stellate cells in vitro and in
      vivo. Because, even at the whole liver level, increased expression of NCX mRNA
      became observable after induction of liver fibrosis, it is suggested that NCX
      expression serves a useful diagnostic marker of liver fibrosis or cirrhosis.

PMID- 9560287
TI  - Cloning and characterization of a potassium-coupled amino acid transporter.
AB  - Active solute uptake in bacteria, fungi, plants, and animals is known to be
      mediated by cotransporters that are driven by Na+ or H+ gradients. The present
      work extends the Na+ and H+ dogma by including the H+ and K+ paradigm.
      Lepidopteran insect larvae have a high K+ and a low Na+ content, and their midgut
      cells lack Na+/K+ ATPase. Instead, an H+ translocating, vacuolar-type ATPase
      generates a voltage of approximately -240 mV across the apical plasma membrane of
      so-called goblet cells, which drives H+ back into the cells in exchange for K+,
      resulting in net K+ secretion into the lumen. The resulting inwardly directed K+
      electrochemical gradient serves as a driving force for active amino acid uptake
      into adjacent columnar cells. By using expression cloning with Xenopus laevis
      oocytes, we have isolated a cDNA that encodes a K+-coupled amino acid transporter
      (KAAT1). We have cloned this protein from a larval lepidopteran midgut (Manduca
      sexta) cDNA library. KAAT1 is expressed in absorptive columnar cells of the
      midgut and in labial glands. When expressed in Xenopus oocytes, KAAT1 induced
      electrogenic transport of neutral amino acids but excludes alpha
      (methylamino)isobutyric acid and charged amino acids resembling the mammalian
      system B. K+, Na+, and to a lesser extent Li+ were accepted as cotransported
      ions, but K+ is the principal cation, by far, in living caterpillars. Moreover,
      uptake was Cl(-)-dependent, and the K+/Na+ selectivity increased with
      hyperpolarization of oocytes, reflecting the increased K+/Na+ selectivity with
      hyperpolarization observed in midgut tissue. KAAT1 has 634 amino acid residues
      with 12 putative membrane spanning domains and shows a low level of identity with
      members of the Na+ and Cl(-)-coupled neurotransmitter transporter family.

PMID- 9560289
TI  - Compartmentalized expression of two structurally and functionally distinct 4
      coumarate:CoA ligase genes in aspen (Populus tremuloides).
AB  - 4-Coumarate:CoA ligases (4CLs, EC 6.2.1.12) are a group of enzymes necessary for
      maintaining a continuous metabolic flux for the biosynthesis of plant
      phenylpropanoids, such as lignin and flavonoids, that are essential to the
      survival of plants. So far, various biochemical and molecular studies of plant
      4CLs seem to suggest that 4CL isoforms in plants are functionally
      indistinguishable in mediating the biosynthesis of these phenolics. However, we
      have discovered two functionally and structurally distinct 4CL genes, Pt4CL1 and
      Pt4CL2 (63% protein sequence identity), that are differentially expressed in
      aspen (Populus tremuloides). The Escherichia coli-expressed and purified Pt4CL1
      and Pt4CL2 proteins exhibited highly divergent substrate preference as well as
      specificity that reveal the association of Pt4CL1 with the biosynthesis of
      guaiacyl-syringyl lignin and the involvement of Pt4CL2 with other phenylpropanoid
      formation. Northern hybridization analysis demonstrated that Pt4CL1 mRNA is
      specifically expressed in lignifying xylem tissues and Pt4CL2 mRNA is
      specifically expressed in epidermal layers in the stem and the leaf, consistent
      with the promoter activities of Pt4CL1 and Pt4CL2 genes based on the heterologous
      promoter-beta-glucouronidase fusion analysis. Thus, the expression of Pt4CL1 and
      Pt4CL2 genes is compartmentalized to regulate the differential formation of
      phenylpropanoids that confer different physiological functions in aspen; Pt4CL1
      is devoted to lignin biosynthesis in developing xylem tissues, whereas Pt4CL2 is
      involved in the biosynthesis of other phenolics, such as flavonoids, in epidermal
      cells.

PMID- 9560288
TI  - Association of the Arabidopsis CTR1 Raf-like kinase with the ETR1 and ERS
      ethylene receptors.
AB  - In Arabidopsis thaliana, signal transduction of the hormone ethylene involves at
      least two receptors, ETR1 and ERS, both of which are members of the two-component
      histidine protein kinase family that is prevalent in prokaryotes. The pathway
      also contains a negative regulator of ethylene responses, CTR1, which closely
      resembles members of the Raf protein kinase family. CTR1 is thought to act at or
      downstream of ETR1 and ERS based on double mutant analysis; however, the
      signaling mechanisms leading from ethylene perception to the regulation of CTR1
      are unknown. By using the yeast two-hybrid assay, we detected a specific
      interaction between the CTR1 amino-terminal domain and the predicted histidine
      kinase domain of ETR1 and ERS. We subsequently verified these interactions by
      using an in vitro protein association assay(s). In addition, we determined that
      the amino-terminal domain of CTR1 can associate with the predicted receiver
      domain of ETR1 in vitro. Based on deletion analysis, the portion of CTR1 that
      interacts with ETR1 roughly aligns with the regulatory region of Raf kinases.
      These physical associations support the genetic evidence that CTR1 acts in the
      pathway of ETR1 and ERS and suggest that these interactions could be involved in
      the regulation of CTR1 activity.

PMID- 9560290
TI  - Visual memory-deficit amnesia: a distinct amnesic presentation and etiology.
AB  - We describe a form of amnesia, which we have called visual memory-deficit
      amnesia, that is caused by damage to areas of the visual system that store visual
      information. Because it is caused by a deficit in access to stored visual
      material and not by an impaired ability to encode or retrieve new material, it
      has the otherwise infrequent properties of a more severe retrograde than
      anterograde amnesia with no temporal gradient in the retrograde amnesia. Of the
      11 cases of long-term visual memory loss found in the literature, all had amnesia
      extending beyond a loss of visual memory, often including a near total loss of
      pretraumatic episodic memory. Of the 6 cases in which both the severity of
      retrograde and anterograde amnesia and the temporal gradient of the retrograde
      amnesia were noted, 4 had a more severe retrograde amnesia with no temporal
      gradient and 2 had a less severe retrograde amnesia with a temporal gradient.

PMID- 9560291
TI  - The hypoglossal canal and the origin of human vocal behavior.
AB  - The mammalian hypoglossal canal transmits the nerve that supplies the muscles of
      the tongue. This canal is absolutely and relatively larger in modern humans than
      it is in the African apes (Pan and Gorilla). We hypothesize that the human tongue
      is supplied more richly with motor nerves than are those of living apes and
      propose that canal size in fossil hominids may provide an indication about the
      motor coordination of the tongue and reflect the evolution of speech and
      language. Canals of gracile Australopithecus, and possibly Homo habilis, fall
      within the range of extant Pan and are significantly smaller than those of modern
      Homo. The canals of Neanderthals and an early "modern" Homo sapiens (Skhul 5), as
      well as of African and European middle Pleistocene Homo (Kabwe and Swanscombe),
      fall within the range of extant Homo and are significantly larger than those of
      Pan troglodytes. These anatomical findings suggest that the vocal capabilities of
      Neanderthals were the same as those of humans today. Furthermore, the vocal
      abilities of Australopithecus were not advanced significantly over those of
      chimpanzees whereas those of Homo may have been essentially modern by at least
      400,000 years ago. Thus, human vocal abilities may have appeared much earlier in
      time than the first archaeological evidence for symbolic behavior.

PMID- 9560292
TI  - The periodontopathogen Porphyromonas gingivalis binds iron protoporphyrin IX in
      the mu-oxo dimeric form: an oxidative buffer and possible pathogenic mechanism.
AB  - Mossbauer spectroscopy was used to re-evaluate iron protoporphyrin IX, FePPIX,
      binding and the chemical nature of the black iron porphyrin pigment of
      Porphyromonas gingivalis. We demonstrate that FePPIX is bound to the cell in the
      mu-oxo dimeric form, [Fe(III)PPIX]2O, and that the iron porphyrin pigment is also
      composed of this material. P. gingivalis also assimilated monomeric Fe(II)- and
      Fe(III)PPIX into mu-oxo dimers in vitro. Scatchard analysis revealed a greater
      binding maximum of cells for mu-oxo dimers than for monomeric Fe(III)-or
      Fe(II)PPIX, although the relative affinity constant for the dimers was lower.
      Formation of [Fe(III)PPIX]2O via reactions of Fe(II)PPIX with oxygen, and its
      toxic derivatives, would serve as an oxidative buffer and permit P. gingivalis
      and other black-pigmenting anaerobes to engender and maintain a local anaerobic
      environment. Tying up of free oxygen species with iron protoporphyrin IX would
      also reduce and limit Fe(II)PPIX-mediated oxygen-radical cell damage. More
      importantly, formation of a cell-surface mu-oxo dimer layer may function as a
      protective barrier against assault by reactive oxidants generated by neutrophils.
      Selective interference with these mechanisms would offer the possibility of
      attenuating the pathogenicity of P. gingivalis and other iron protoporphyrin IX
      binding pathogens whose virulence is regulated by this reactive molecule.

PMID- 9560293
TI  - Mucus glycoproteins from pig gastric mucosa: different mucins are produced by the
      surface epithelium and the glands.
AB  - An antibody (PGM2B) recognizing a pig gastric-mucin apoprotein reacts with the
      surface epithelium of pig gastric mucosa. Virtually no reactivity was observed
      over the mucin-producing cells in the glands, which were recognized by the GlcNAc
      selective Griffonia simplicifolia II (GSA-II) lectin. Mucins from the glandular
      tissue of the cardiac region, corpus and antrum were purified using isopycnic
      density-gradient centrifugation in CsCl/guanidinium chloride. In the cardiac
      region, two major mucin populations at 1.5 and 1.4 g/ml were identified. The high
      density population reacted preferentially with the PGM2B antibody and resembled
      mucins from the surface epithelium of this region, whereas the low-density
      population reacted strongly with the GSA-II lectin and appeared to originate from
      the glands. In the glandular tissue of corpus, a component with strong GSA-II
      lectin reactivity, which was distinctly different from the surface mucins from
      this region, was found at 1.4 g/ml, thus resembling the gland component from the
      cardiac region. Mucins from antrum glandular tissue contained at least two GSA-II
      lectin-reactive populations banding at 1.5 and 1.4 g/ml, respectively. Gland
      mucins from all regions were large oligomeric glycoproteins and heterogeneous
      with respect to charge properties, as shown by using rate-zonal centrifugation
      and ion-exchange HPLC, respectively. Gel chromatography of mucin glycopeptides
      showed that gland mucins from antrum and corpus contained significantly longer
      glycosylated domains than those from the surface mucosa. Thus, mucins from pig
      gastric glandular tissue comprise a number of large and oligomeric glycoproteins
      that differ from those from the surface epithelium in buoyant density, apoprotein
      structure and carbohydrate substitution.

PMID- 9560295
TI  - The mechanism of catalysis and the inhibition of the Bacillus cereus zinc
      dependent beta-lactamase.
AB  - The plot of kcat/Km against pH for the Bacillus cereus 569/H beta-lactamase class
      B catalysed hydrolysis of benzylpenicillin and cephalosporin indicates that there
      are three catalytically important groups, two of pKa 5.6+/-0.2 and one of pKa
      9.5+/-0.2. Below pH 5 there is an inverse second-order dependence of reactivity
      upon hydrogen ion concentration, indicative of the requirement of two basic
      residues for catalysis. These are assigned to zinc(II)-bound water and Asp-90,
      both with a pKa of 5.6+/-0.2. A thiol, N-(2'-mercaptoethyl)-2-phenylacetamide, is
      an inhibitor of the class B enzyme with a Ki of 70 microM. The pH-dependence of
      Ki shows similar pH inflections to those observed in the catalysed hydrolysis of
      substrates. The pH-independence of Ki between pH 6 and 9 indicates that the pKa
      of zinc(II)-bound water must be 5.6 and not the higher pKa of 9.5. The kinetic
      solvent isotope effect on kcat/Km is 1.3+/-0.5 and that on kcat is 1.5. There is
      no effect on reactivity by either added zinc(II) or methanol. The possible
      mechanisms of action for the class B beta-lactamase are discussed, and it is
      concluded that zinc(II) acts as a Lewis acid to stabilize the dianionic form of
      the tetrahedral intermediate and to provide a hydroxide-ion bound nucleophile,
      whereas the carboxylate anion of Asp-90 acts as a general base to form the
      dianion and also, presumably, as a general acid catalyst facilitating C-N bond
      fission.

PMID- 9560294
TI  - Activation of the signal transducer gp130 by interleukin-11 and interleukin-6 is
      mediated by similar molecular interactions.
AB  - The transmembrane glycoprotein gp130 is involved in many cytokine-mediated
      cellular responses and acts therein as the signal transducing receptor subunit.
      Interleukin-6 (IL-6) and interleukin-11 (IL-11), in complex with their specific
      alpha-receptors, homodimerize gp130 and, as a consequence, activate the Janus
      kinase (Jak)/signal transducer and activator of transcription (STAT) signalling
      pathway in their target cells. So far, it is not clear whether gp130 is bound to
      these cytokines and their specific alpha-receptor subunits through identical or
      different epitopes. In order to study the interaction of IL-11 and IL-11R with
      human gp130 the soluble form of the recently cloned human IL-11R was expressed in
      baculovirus-infected insect cells. By a coprecipitation binding-assay it is
      demonstrated that IL-11 and IL-6 compete for binding to gp130. Using deletion and
      point mutants of gp130 it is shown that IL-11-IL-11R and IL-6-IL-6R recognize
      overlapping binding motifs on gp130. Moreover, using well-established Jak
      deficient cell lines we demonstrate that STAT activation by IL-11 requires Jak1.
      Taken together, our data support the concept that IL-6 and IL-11 activate gp130
      by very similar molecular mechanisms.

PMID- 9560296
TI  - Control of growth and differentiation of normal human epithelial cells through
      the manipulation of reactive nitrogen species.
AB  - In this work, we addressed the issue of whether exogenous NO and ONOO-
      (peroxynitrite) are able to alter growth, viability and/or differentiation of
      normal epithelial cells using cultured normal human keratinocytes as a model. 3
      Morpholino-sydnonimine (SIN-1), a donor of both NO and O2(-)., leading to the
      production of ONOO-, dose-dependently inhibited growth of human keratinocytes
      without loss of viability. This inhibitory effect was lowered when SIN-1 was
      transformed into a pure NO donor by scavenging O2(-). with superoxide
      dismutase/catalase. Finally, scavenging NO release from SIN-1 with carboxy-1H
      imidazol-1-yloxy,2-(4-carboxyp henyl)-4,5-dihydro-4,4,5,5 -tetramethyl-3-oxide
      (PTIO) resulted in a loss of the inhibitory effect of SIN-1. Together these
      findings suggest that both ONOO- and NO exert a growth inhibitory effect on human
      keratinocytes without cytotoxicity. Further support for this conclusion came from
      the treatment of human keratinocytes with the NO. donor propanamine 3-(2-hydroxy
      2-nitroso-1-propyl hydrazino) or with authentic peroxynitrite. Moreover, only SIN
      1 or peroxynitrite, and not NO, was able to trigger the expression of markers of
      terminal differentiation in human keratinocytes. From a physiological
      perspective, the ability of peroxynitrite, a known genotoxic and potentially
      carcinogenic agent, to direct proliferating keratinocytes towards terminal
      differentiation may be crucial to protect the genomic stability of this barrier
      epithelium.

PMID- 9560298
TI  - Human cathepsin K cleaves native type I and II collagens at the N-terminal end of
      the triple helix.
AB  - Cathepsin K (EC 3.4.22.38) is a recently described enzyme that has been shown to
      cleave type I collagen in its triple helix. The aim of this study was to
      determine if it also cleaves type II collagen in the triple helix and to identify
      the helical cleavage site(s) in types I and II collagens. Soluble human and
      bovine type II collagen, and rat type I collagen, were incubated with cathepsin K
      before the reaction was stopped with trans-epoxysuccinyl-l-leucylamido-(4
      guanidino)butane (E-64). Analysis by SDS/PAGE of the collagen digests showed that
      optimal activity of cathepsin K against native type II collagen was between pH
      5.0 and 5.5 and against denatured collagen between pH 4.0 and 7.0. The enzyme
      cleaved telopeptides as well as the alpha1(II) chains, generating multiple
      fragments in the range 90-120 kDa. The collagenolytic activity was not due to a
      contaminating metalloenzyme or serine proteinase as it was not inhibited by 1,10
      phenanthroline, EDTA or 3,4-dichloroisocoumarin. Western blotting with anti
      peptide antibodies to different regions of the alpha1(II) chain suggested that
      cathepsin K cleaved native alpha1(II) chains in the N-terminal region of the
      helical domain rather than at the well-defined collagenase cleavage site. This
      was confirmed by N-terminal sequencing of one of the fragments, revealing
      cleavage at a Gly-Lys bond, 58 residues from the N-terminus of the helical
      domain. By using a similar approach, cathepsin K was found to cleave native type
      I collagen close to the N-terminus of its triple helix. These results indicate
      that cathepsin K could have a role in the turnover of type II collagen, as well
      as type I collagen.

PMID- 9560297
TI  - Iron loading of isolated rat hepatocytes inhibits asialoglycoprotein receptor
      dynamics and induces formation of rat hepatic lectin-1 [correction of leptin-1]
      (RHL-1) oligomers.
AB  - The major subunit [rat hepatic lectin-1 (RHL-1)] of the asialoglycoprotein (ASGP)
      receptor mediates endocytosis of the iron-binding protein lactoferrin (Lf) by
      isolated rat hepatocytes, yet iron loading of cultured adult rat hepatocytes
      increases the binding and endocytosis of Lf while greatly inhibiting the uptake
      of desialylated ligand. In the present study, we determined whether the iron
      induced Lf-binding site is RHL-1 and examined the nature of the iron-induced
      block in ASGP receptor endocytic function. Isolated rat hepatocytes increased
      their non-haem iron content from 70 to 470 p.p. b. following incubation with
      ferric ammonium citrate (<=100 microgram/ml). These conditions blocked
      internalization of 125I-asialo-orosomucoid (ASOR) by approximately 90% but
      increased 125I-Lf endocytosis by 40%. ASOR and anti-RHL-1 sera blocked the
      binding and endocytosis of 125I-Lf on control cells but not on iron-loaded cells,
      indicating that the iron-induced Lf-binding site on hepatocytes is not RHL-1.
      Iron-loading of hepatocytes in the presence or absence of excess ASOR did not
      significantly alter the number of active ASGP receptors on the cell surface. In
      contrast, iron-loading decreased the number of active intracellular receptors by
      40% and blocked the uptake of 125I-ASOR prebound to the cells by approximately
      80%. Under these conditions, we found an iron-dependent evolution of 88 and 140
      kDa RHL-1-containing, beta-mercaptoethanol-sensitive multimers that constituted
      up to 34 and 23%, respectively, of total immunodetectable RHL-1. We propose that
      iron-induced formation of cystinyl-linked RHL-1-containing multimers inhibits
      ASGP receptor movement between cell surface and interior and disrupts acylation
      of intracellular receptors.

PMID- 9560299
TI  - Bisecting GlcNAc structure is implicated in suppression of stroma-dependent
      haemopoiesis in transgenic mice expressing N-acetylglucosaminyltransferase III.
AB  - Several sugar structures have been reported to be necessary for haemopoiesis. We
      analysed the haematological phenotypes of transgenic mice expressing beta-1,4 N
      acetylglucosaminyltransferase III (GnT-III), which forms bisecting N
      acetylglucosamine on asparagine-linked oligosaccharides. In the transgenic mice,
      the GnT-III activity was elevated in bone marrow, spleen and peripheral blood and
      in isolated mononuclear cells from these tissues, whereas no activity was found
      in these tissues of wild-type mice. Stromal cells after long-term cultures of
      transgenic-derived bone marrow and spleen cells also showed elevated GnT-III
      activity, compared with an undetectable activity in wild-type stromal cells. As
      judged by HPLC analysis, lectin blotting and lectin cytotoxicity assay, bisecting
      GlcNAc residues were increased on both blood cells and stromal cells from bone
      marrow and spleen in transgenic mice. The transgenic mice displayed spleen
      atrophy, hypocellular bone marrow and pancytopenia. Bone marrow cells and spleen
      cells from transgenic mice produced fewer haemopoietic colonies. After lethal
      irradiation followed by bone marrow transplantation, transgenic recipient mice
      showed pancytopenia compared with wild-type recipient mice. Bone marrow cells
      from transgenic donors gave haematological reconstitution at the same level as
      wild-type donor cells. In addition, non-adherent cell production was decreased in
      long-term bone marrow cell cultures of transgenic mice. Collectively these
      results indicate that the stroma-supported haemopoiesis is compromised in
      transgenic mice expressing GnT-III, providing the first demonstration that the N
      glycans have some significant roles in stroma-dependent haemopoiesis.

PMID- 9560301
TI  - Overexpression of prothymosin alpha accelerates proliferation and retards
      differentiation in HL-60 cells.
AB  - Prothymosin alpha (ProTalpha) is an acidic nuclear protein the expression of
      which is related to the proliferation and differentiation processes in mammalian
      cells. In the present study we have stably transfected HL-60 cells, a biological
      system that allows the study of both proliferation and differentiation, with
      recombinant vectors encoding sense and antisense ProTalpha mRNA. In the HL-60
      cell clones overexpressing ProTalpha we observed an acceleration in the growth
      rate, whereas expression of the antisense orientation showed the opposite effect.
      Moreover, cell-cycle analysis demonstrated that the G1-phase was shortened in the
      cells expressing the sense construct. Before studying how ProTalpha affects
      differentiation, we showed that the down-regulation of ProTalpha gene during
      differentiation occurs in all mammalian cell lines (HL-60, K562, U937, MEL C88,
      N2A and PC12) analysed. The biological effect evoked by the induction of the
      ProTalpha sense vector was the retardation of cell differentiation, although
      expression of the antisense construct showed no effect on differentiation. In
      conclusion, our findings provide evidence that ProTalpha is directly implicated
      in cellular proliferation and that the maintenance of high levels of ProTalpha
      inside HL-60 cells is incompatible with their ability to differentiate.

PMID- 9560302
TI  - Functional consequences of relocating the C-terminal calmodulin-binding
      autoinhibitory domains of the plasma membrane Ca2+ pump near the N-terminus.
AB  - A mutant of the plasma membrane Ca2+ pump (PMCA) called (nCI)hPMCA4b(ct120), in
      which the C-terminal regulatory segment including the calmodulin-binding
      autoinhibitory domains C and I had been relocated near the N-terminus, has been
      expressed in COS-1 cells. The measurements of Ca2+ transport in microsomal
      preparations showed that the rearranged enzyme was functional. The activity of
      the (nCI)hPMCA4b(ct120) mutant was compared with those of the wild-type hPMCA4b
      and the fully active calmodulin-insensitive mutant hPMCA4b(ct120). In the absence
      of calmodulin the activity of (nCI)hPMCA4b(ct120) was higher than that of hPMCA4b
      but only 45% of that of hPMCA4b(ct120). Mutant (nCI)hPMCA4b(ct120) exhibited an
      apparent affinity for Ca2+ similar to that of hPMCA4b, typical of the inhibited
      state of the enzyme. Calmodulin at concentrations that fully activated hPMCA4b
      increased the activity of (nCI)hPMCA4b(ct120) to 68% of that of hPMCA4b(ct120).
      The lower maximal activity of (nCI)hPMCA4b(ct120) was not due to a lower affinity
      for calmodulin because the concentration of calmodulin required for half-maximal
      activation of (nCI)hPMCA4b(ct120) was equal to that of the wild-type hPMCA4b.
      These results indicate that (1) the disturbance of the N-terminal region of the
      PMCA by the insertion of the C-terminal segment decreased the ability of the pump
      to transport Ca2+, and (2) the calmodulin-binding autoinhibitory domain was still
      able to access its acceptor site from the N-terminal end of the molecule.
      However, although the calmodulin-binding and inhibitory functions of the C-domain
      were fully preserved, the I domain at its new position seemed less effective at
      inhibiting the pump.

PMID- 9560300
TI  - Proteoglycans in macrophages: characterization and possible role in the cellular
      uptake of lipoproteins.
AB  - The murine macrophage cell line J774 was incubated with [35S]sulphate. The cell
      associated 35S-labelled macromolecules were shown to be proteoglycans and
      glycosaminoglycans in similar amounts. The possible presence of cell-surface
      proteoglycans was investigated by incubating [35S]sulphate-labelled cells with
      trypsin for 15 min. The released material contained approx. 70% free
      glycosaminoglycan chains and 30% proteoglycans. The latter component was
      demonstrated by HNO2 treatment to contain heparan sulphate. In the total cell
      fraction not treated with trypsin a small but significant portion was shown to be
      chondroitin sulphate proteoglycan. The cell-associated glycosaminoglycans
      contained both chondroitin sulphate and heparan sulphate. To investigate possible
      biological functions of cell-surface proteoglycans in macrophages, cells were
      incubated with NaClO3 to inhibit sulphation of proteoglycans and beta-d-xyloside
      to abrogate proteoglycan expression. The uptake of oxidized 125I
      tyraminylcellobiose-labelled low-density lipoprotein (125I-TC-LDL) was typically
      two to three times higher than that of native 125I-TC-LDL in untreated J774
      cells. The cellular uptake at 37 degreesC of native 125I-TC-LDL was decreased 25%
      after both NaClO3 and xyloside treatment, whereas the uptake of oxidized 125I-TC
      LDL was decreased 35% after both types of treatment. The mRNA levels for the
      scavenger receptor A-II and the LDL receptor were not affected by NaClO3 or
      xyloside treatment. Furthermore, fluid-phase endocytosis, measured as uptake of
      horseradish peroxidase, and receptor-mediated endocytosis, measured as uptake of
      125I-TC-ovalbumin, were not affected by NaClO3 treatment of J774 cells. Removal
      of cell-surface chondroitin sulphate with chondroitinase ABC decreased only the
      binding of native 125I-TC-LDL, whereas removal of heparan sulphate with
      heparitinase decreased the binding of both oxidized and native 125I-TC-LDL.
      Addition of lipoprotein lipase increased the uptake of oxidized 125I-TC-LDL 1.7
      times and the uptake of native 125I-TC-LDL 2.1 times. The binding of the former
      was more sensitive to NaClO3 treatment than the latter. The results presented
      support the notion that some of the uptake pathways for lipoproteins in the foam
      cell-forming macrophages depend on the presence of cell-surface heparan sulphate
      and chondroitin sulphate.

PMID- 9560303
TI  - Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis
      retinoic acid is mediated via retinoic acid receptor alpha.
AB  - Thymocytes can be induced to undergo apoptotic cell death by activation through
      the T-cell receptor (TCR). This process requires macromolecular synthesis and has
      been shown to be inhibited by retinoic acids (RAs). Two groups of nuclear
      receptors for RAs have been identified: retinoic acid receptors (RARs) and
      retinoid X receptors (RXRs). All-trans-RA is the high-affinity ligand for RARs,
      and 9-cis-RA additionally binds to RXRs with high affinity. Because 9-cis-RA is
      much more potent in inhibiting TCR-mediated death than all-trans-RA, it was
      suggested that RXRs participate in the process. In the present study various
      synthetic retinoid analogues were used to address this question further. The
      results presented suggest that the inhibitory effect of RAs on activation-induced
      death of thymocytes is mediated via RARalpha, because (1) it can be reproduced by
      various RARalpha analogues both in vitro and in vivo, (2) the effect of RAs can
      be inhibited by the addition of an RARalpha antagonist, (3) CD4+CD8+thymocytes,
      which die on TCR stimulation, express RARalpha. Stimulation of RARgamma, in
      contrast, enhances the activation-induced death of thymocytes and inhibits its
      prevention by RARalpha stimulation. RXR co-stimulation suspends this inhibitory
      effect of RARgamma and permits the preventive function of RARalpha on activation
      induced death. Our results suggest a complex interaction between the various
      isoforms of retinoid receptors and demonstrate that low (physiological)
      concentrations of all-trans-RA do not affect the activation-induced death of
      thymocytes because the RARalpha-mediated inhibitory and the RARgamma-mediated
      enhancing pathways are in balance, whereas if 9-cis-RA is formed, additional
      stimulation of RXRs permits the inhibitory action of RARalpha.

PMID- 9560304
TI  - Pseudomonas cellulose-binding domains mediate their effects by increasing enzyme
      substrate proximity.
AB  - To investigate the mode of action of cellulose-binding domains (CBDs), the Type
      II CBD from Pseudomonas fluorescens subsp. cellulosa xylanase A (XYLACBD) and
      cellulase E (CELECBD) were expressed as individual entities or fused to the
      catalytic domain of a Clostridium thermocellum endoglucanase (EGE). The two CBDs
      exhibited similar Ka values for bacterial microcrystalline cellulose (CELECBD,
      1.62x10(6) M-1; XYLACBD, 1.83x10(6) M-1) and acid-swollen cellulose (CELECBD,
      1.66x10(6) M-1; XYLACBD, 1.73x10(6) M-1). NMR spectra of XYLACBD titrated with
      cello-oligosaccharides showed that the environment of three tryptophan residues
      was affected when the CBD bound cellohexaose, cellopentaose or cellotetraose. The
      Ka values of the XYLACBD for C6, C5 and C4 cello-oligosaccharides were estimated
      to be 3.3x10(2), 1.4x10(2) and 4.0x10(1) M-1 respectively, suggesting that the
      CBD can accommodate at least six glucose molecules and has a much higher affinity
      for insoluble cellulose than soluble oligosaccharides. Fusion of either the
      CELECBD or XYLACBD to the catalytic domain of EGE potentiated the activity of the
      enzyme against insoluble forms of cellulose but not against
      carboxymethylcellulose. The increase in cellulase activity was not observed when
      the CBDs were incubated with the catalytic domain of either EGE or XYLA, with
      insoluble cellulose and a cellulose/hemicellulose complex respectively as the
      substrates. Pseudomonas CBDs did not induce the extension of isolated plant cell
      walls nor weaken cellulose paper strips in the same way as a class of plant cell
      wall proteins called expansins. The XYLACBD and CELECBD did not release small
      particles from the surface of cotton. The significance of these results in
      relation to the mode of action of Type II CBDs is discussed.

PMID- 9560306
TI  - Thiol-independent interaction of protein disulphide isomerase with type X
      collagen during intra-cellular folding and assembly.
AB  - Protein disulphide isomerase (PDI) has been shown to be a multifunctional protein
      capable of catalysing disulphide-bond formation and isomerization, and of
      participating as a non-catalytic subunit of prolyl 4-hydroxylase (P4-H) and
      microsomal triacylglycerol transfer protein. It has also been proposed to
      function as a molecular chaperone during the refolding of denatured proteins in
      vitro. To investigate its potential role as a molecular chaperone within a
      cellular context, we studied the folding, modification and assembly of type X
      collagen in semi-permeabilized cells. Using this approach, we demonstrate that
      depletion of ATP has no effect on the rate or extent of helix formation,
      indicating that the individual triple helical regions do not interact with the
      molecular chaperone immunoglobulin heavy-chain binding protein (BiP). However,
      PDI was shown to interact transiently with type X during helix formation in a
      role related to its function as the beta subunit of P4-H. Once the collagen
      triple helix was formed, PDI re-associated, indicating a role in preventing the
      premature assembly of this molecule into higher-order structures. This
      interaction was not thiol dependent, as a type X polypeptide that did not contain
      any cysteine residues was able to fold correctly and interact with PDI. Both PDI
      and the collagen-binding protein hsp47 showed a similar pH-dependent interaction
      with folded collagen, dissociating when the pH was lowered to pH 6.0. These
      results suggest a role for PDI in chaperoning type X collagen during its
      transport through the cell.

PMID- 9560307
TI  - Effects of pH on the structure and function of neuronal nitric oxide synthase.
AB  - We investigated how pH affects rat brain neuronal nitric oxide synthase (nNOS)
      with regard to spin-state equilibrium and the thiolate ligand bond of the haem
      group, catalytic activity, and monomerleft and right arrow dimer equilibrium. At
      neutral pH, nNOS containing 1 equiv. of (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4)
      per dimer was mostly high-spin (lambdamax at 398 nm), whereas the BH4-free enzyme
      consisted of a mixture of the high-spin and two low-spin forms (lambdamax at 418
      nm, and at 376 and 456 nm respectively). With BH4-free nNOS, an appreciable high
      spin fraction was only observed between pH 7 and 8; at pH 6 and 9, the 418 and
      376/456 nm low-spin forms predominated respectively. With nNOS containing 1
      equiv. of BH4 per dimer, similar observations were made, but these involved only
      half of the enzyme; the other half, presumably the BH4-containing subunits,
      remained high-spin. Since the spin state in the BH4-free subunit appeared little
      affected by the state of the other subunit, we conclude that, in dimeric nNOS,
      the two haem groups function independently. Low pH destabilized thiolate binding
      and the interaction between NOS subunits, as indicated by CO-binding studies and
      gel electrophoresis respectively. Formation of l-citrulline was optimal between
      pH 7.0 and 7.5; the decrease in NOS activity at lower pH proved to be due to
      uncoupling of NADPH oxidation, resulting in increased formation of H2O2. At high
      pH strict coupling of l-arginine and NADPH oxidation was maintained, even in the
      absence of exogenous BH4. The possible pathophysiological implications of the
      uncoupling at low pH are discussed.

PMID- 9560305
TI  - Determinants of the substrate specificity of human cytochrome P-450 CYP2D6:
      design and construction of a mutant with testosterone hydroxylase activity.
AB  - Cytochrome P-450 CYP2D6, human debrisoquine hydroxylase, metabolizes more than 30
      prescribed drugs, the vast majority of which are small molecules containing a
      basic nitrogen atom. In contrast, the similar mouse protein Cyp2d-9 was first
      characterized as a testosterone 16alpha-hydroxylase. No common substrates have
      been reported for the two enzymes. Here we investigate the structural basis of
      this difference in substrate specificity. We have earlier used a combination of
      NMR data and homology modelling to generate a three-dimensional model of CYP2D6
      [Modi, Paine, Sutcliffe, Lian, Primrose, Wolf, C.R. and Roberts (1996)
      Biochemistry 35, 4541-4550]. We have now generated a homology model of Cyp2d-9
      and compared the two models to identify specific amino acid residues that we
      believe form the substrate-binding site in each protein and therefore influence
      catalytic selectivity. Although there are many similarities in active site
      structure, the most notable difference is a phenylalanine residue (Phe-483) in
      CYP2D6, which in the model is located such that the bulky phenyl ring is
      positioned across the channel mouth, thus limiting the size of substrate that can
      access the active site. In Cyp2d-9, the corresponding position is occupied by an
      isoleucine residue, which imposes fewer steric restraints on the size of
      substrate that can access the active site. To investigate whether the amino acid
      residue at this position does indeed influence the catalytic selectivity of these
      enzymes, site-directed mutagenesis was used to change Phe-483 in CYP2D6 to
      isoleucine and also to tryptophan. CYP2D6, Cyp2d-9 and both mutant CYP2D6
      proteins were co-expressed with NADPH cytochrome P-450 reductase as a functional
      mono-oxygenase system in Escherichia coli and their relative catalytic activities
      towards bufuralol and testosterone were determined. All four proteins exhibited
      catalytic activity towards bufuralol but only Cyp2d-9 catalysed the formation of
      16alpha-hydroxytesterone. Uniquely, the CYP2D6F483I mutant acquired the ability
      to metabolize testosterone to a novel product, which was identified by MS and
      proton NMR spectroscopy as 15alpha-hydroxytestosterone. NMR spin relaxation
      experiments were used to measure distances between the haem iron and protons of
      testosterone bound to the CYP2D6F483I mutant. These experiments demonstrate that
      very minor modifications to the active site structure of CYP2D6 can have a
      profound influence on the substrate specificity of the enzyme.

PMID- 9560309
TI  - Somatotropin-dependent decrease in fatty acid synthase mRNA abundance in 3T3
      F442A adipocytes is the result of a decrease in both gene transcription and mRNA
      stability.
AB  - Somatotropin (ST) markedly decreases lipogenesis, fatty acid synthase (FAS)
      enzyme activity and mRNA abundance in pig adipocytes. The present study was
      conducted to determine whether the decrease in FAS mRNA in 3T3-F442A adipocytes
      was the result of a decrease in transcription of the FAS gene and/or a change in
      FAS mRNA stability. Insulin increased the abundance of FAS mRNA 2-13-fold and
      fatty acid synthesis 3-7-fold. Somatotropin decreased the stimulatory effect of
      insulin on the abundance of FAS mRNA and lipogenesis by 40-70% and 20-60%
      respectively. Subsequent run-on analyses demonstrated that the decrease observed
      in FAS mRNA in response to ST was associated with an 82% decrease in
      transcription; ST significantly shortened the half-life of FAS mRNA from 35 to 11
      h. To corroborate the run-on analyses, cells were stably transfected with a pFAS
      CAT5 (in which CAT stands for chloramphenicol acetyltransferase) reporter
      construct that contained 2195 bp of the 5' flanking region of the rat FAS gene.
      Insulin treatment increased FAS-CAT activity 4.7-fold. When ST was added to the
      insulin-containing medium there was an approx. 60% reduction in FAS-CAT activity.
      In summary, our results indicate that ST decreases FAS mRNA levels and that this
      is the result of a marked decrease in both transcription of the FAS gene and
      stability of the FAS mRNA.

PMID- 9560308
TI  - A novel assay in vitro of human islet amyloid polypeptide amyloidogenesis and
      effects of insulin secretory vesicle peptides on amyloid formation.
AB  - Human islet amyloid polypeptide (IAPP) is a 37-residue peptide that is co
      secreted with insulin by the beta-cell and might be involved in the pathogenesis
      of non-insulin-dependent diabetes mellitus. We developed an improved assay in
      vitro based on the fluorescence of bound thioflavin T to study factors affecting
      amyloidogenesis. Monomeric IAPP formed amyloid fibrils, as detected by increased
      fluorescence and by electron microscopy. Fluorimetric analysis revealed that the
      initial rate of amyloid formation was: (1) proportional to the peptide monomer
      concentration, (2) maximal at pH 9.5, (3) maximal at 200 mMKCl, and (4)
      proportional to temperature from 4 to 37 degreesC. We found that 5-fold and 10
      fold molar excesses of proinsulin inhibited fibril formation by 39% and 59%
      respectively. Insulin was somewhat more potent with 5-fold and 10-fold molar
      excesses inhibiting fibril formation by 69% and 73% respectively, whereas C
      peptide had no effect at these concentrations. Thus at physiological ratios of
      IAPP to insulin, insulin and proinsulin, but not C-peptide, can retard
      amyloidogenesis. Because insulin resistance or hyperglycaemia increase the IAPP
      to-insulin ratio, increased intracellular IAPP compared with insulin expression
      in genetically predisposed individuals might contribute to intracellular amyloid
      formation, beta-cell death and the genesis of non-insulin-dependent diabetes
      mellitus.

PMID- 9560310
TI  - Regulation of integrin function: evidence that bivalent-cation-induced
      conformational changes lead to the unmasking of ligand-binding sites within
      integrin alpha5 beta1.
AB  - The molecular mechanisms that regulate integrin-ligand binding are unknown;
      however, bivalent cations are essential for integrin activity. According to
      recent models of integrin tertiary structure, sites involved in ligand
      recognition are located on the upper face of the seven-bladed beta-propeller
      formed by the N-terminal repeats of the alpha subunit and on the von Willebrand
      factor A-domain-like region of the beta subunit. The epitopes of function
      altering monoclonal antibodies (mAbs) cluster in these regions of the alpha and
      beta subunits; hence these mAbs can be used as probes to detect changes in the
      exposure or shape of the ligand-binding sites. Bivalent cations were found to
      alter the apparent affinity of binding of the inhibitory anti-alpha5 mAbs JBS5
      and 16, the inhibitory anti-beta1 mAb 13, and the stimulatory anti-beta1 mAb
      12G10 to alpha5 beta1. Analysis of the binding of these mAbs to alpha5beta1 over
      a range of Mn2+, Mg2+ or Ca2+ concentrations demonstrated that there was a
      concordance between the ability of cations to elicit conformational changes and
      the ligand-binding potential of alpha5 beta1. Competitive ELISA experiments
      provided evidence that the domains of the alpha5 and beta1 subunits recognized by
      mAbs JBS5/16 and 13/12G10 are spatially close, and that the distance between
      these two domains is increased when alpha5 beta1 is occupied by bivalent cations.
      Taken together, our findings suggest that bivalent cations induce a
      conformational relaxation in the integrin that results in exposure of ligand
      binding sites, and that these sites lie near an interface between the alpha
      subunit beta-propeller and the beta subunit putative A-domain.

PMID- 9560312
TI  - Differential regulation of nicotinic acid-adenine dinucleotide phosphate and cADP
      ribose production by cAMP and cGMP.
AB  - The sea urchin egg has been used as a system to study calcium-release mechanisms
      induced by inositol 1,4,5-trisphosphate (IP3), cADP-ribose (cADPR), and more
      recently, nicotinic acid-adenine dinucleotide phosphate (NAADP). In order that
      cADPR and NAADP may be established as endogenous messengers for calcium release,
      the existence of intracellular enzymes capable of metabolizing these molecules
      must be demonstrated. In addition, intracellular levels of cADPR and NAADP should
      be under the control of extracellular stimuli. It has been shown that cGMP
      stimulates the synthesis of cADPR in the sea urchin egg. The present study shows
      that the sea urchin egg is capable of synthesizing and degrading NAADP. cADPR and
      NAADP synthetic activities appear to be separate, with different cellular
      localizations, pH and temperature optima. We suggest that in the sea urchin egg,
      cADPR and NAADP production may be differentially regulated by receptor-coupled
      second messengers, with cADPR production being regulated by cGMP and NAADP
      production modulated by cAMP.

PMID- 9560313
TI  - Organization and alternative splicing of the murine phospholipase D2 gene.
AB  - Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine, generating
      phosphatidic acid and choline. Mammalian PLD activity derives from a family of
      membrane-associated enzymes that are activated by a wide variety of signal
      transduction events. cDNA species encoding human, mouse and rat PLD1 and PLD2
      have recently been reported. In this study we undertook to determine the
      organization of the mouse PLD2 gene. We report that the gene spans 17.1 kb and
      contains 25 exons. Mouse PLD2 is notable for a relatively GC-rich and large 5'
      untranslated region. Proximal promoter sequences upstream of the first exon
      contain several consensus SP1 sequences (GGGCGG) but lack TATA and CAAT boxes.
      Finally, alternatively spliced cDNA species identified for PLD1 and PLD2 are
      discussed in the context of the PLD2 genomic organization.

PMID- 9560311
TI  - Multiple endosomal recycling pathways in rat adipose cells.
AB  - Adipose and skeletal-muscle cells can translocate several membrane proteins from
      intracellular compartment(s) to the cell surface in an insulin-dependent fashion.
      Among these proteins is Glut4, a physiologically important glucose transporter
      which mediates insulin's effect on blood glucose clearance. Under basal
      conditions, Glut4 is localized in uniform, intracellular membrane vesicles with
      an average diameter of 50-70 nm and a sedimentation coefficient of 100-120 S. The
      nature of this compartment and its trafficking pathway to the plasma membrane is
      still unresolved. We show here that, in addition to Glut4, the aminopeptidase
      gp160 or insulin-responsive aminopeptidase ('IRAP'), sortilin, and an acutely
      recycling population of the insulin-like growth factor-II/mannose 6-phosphate
      receptor, this compartment includes 60% of the intracellular population of the
      transferrin receptor. We used subcellular fractionation, cell-surface
      biotinylation, and radioactive-ligand (125I-transferrin) uptake to demonstrate
      that the transferrin receptor recycles between this compartment and the plasma
      membrane in response to insulin along with Glut4 and other protein components of
      these vesicles. The co-localization of Glut4 and several endosomal markers in the
      terminally differentiated fat-cells during several stages of their cycling
      pathways suggests that the 'Glut4 pathway' may derive from the hormone
      insensitive endosomes of undifferentiated preadipocytes. The insulin receptor is
      excluded from Glut4-containing vesicles in both insulin-stimulated and
      unstimulated adipocytes, and thus it is likely to traffic independently from
      Glut4 through different intracellular compartments. Our data show that, in
      adipose cells, the ligand-dependent recycling pathway of the insulin receptor is
      structurally separated from the ligand-independent pathway of the transferrin
      receptor, and that Glut4 is specifically targetted to the latter.

PMID- 9560314
TI  - Ambient but not incremental oxidant generation effects intercellular adhesion
      molecule 1 induction by tumour necrosis factor alpha in endothelium.
AB  - Proinflammatory cytokines upregulate endothelial adhesion molecule expression,
      thereby initiating the microvascular inflammatory response. We re-evaluated the
      reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of
      intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour
      necrosis factor alpha (TNF-alpha) in vitro. TNF-alpha upregulation of endothelial
      cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by
      the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide
      dismutase, but not by the exogenous (extracellular) administration of the cell
      impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1
      upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome
      bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM
      generation in response to TNF-alpha was not seen using four disparate sensitive
      ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation
      did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-alpha. These
      findings suggest that an ambient background flux of ROMs, generated
      intracellularly, but not their net incremental generation, is necessary for TNF
      alpha to induce ICAM-1 expression in endothelium in vitro.

PMID- 9560315
TI  - Osmotic swelling-induced activation of the extracellular-signal-regulated protein
      kinases Erk-1 and Erk-2 in intestine 407 cells involves the Ras/Raf-signalling
      pathway.
AB  - Human Intestine 407 cells respond to hypo-osmotic stress with a rapid stimulation
      of compensatory ionic conductances accompanied by a transient increase in the
      activity of the extracellular-signal-regulated protein kinases Erk-1 and Erk-2.
      In this study, we examined the upstream regulators of hypotonicity-induced Erk
      1/Erk-2 activation and their possible role in cell-volume regulation. The
      hypotonicity-provoked Erk-1/Erk-2 activation was greatly reduced in cells
      pretreated with the specific mitogen-activated/Erk-activating kinase inhibitor
      PD098059 and was preceded by a transient stimulation of Raf-1. Pretreatment of
      the cells with PMA, GF109203X, wortmannin or Clostridium botulinum C3 exoenzyme
      did not appreciably affect the hypotonicity-provoked Erk-1/Erk-2 stimulation,
      suggesting the osmosensitive signalling pathway to be largely independent of
      protein kinase C and p21(rho). In contrast, expression of dominant negative
      RasN17 completely abolished the hypotonicity-induced Erk-1/Erk-2 activation.
      Stimulation of the swelling-induced ion efflux was independent of activation of
      these mitogen-activated protein kinases, as revealed by hypotonicity-provoked
      isotope efflux from 125I-- and 86Rb+-loaded cells after pretreatment with
      PD098059 and after expression of RasN17. In addition, the epidermal-growth-factor
      induced potentiation of the hypotonicity-provoked anionic response did not depend
      on the increase in Erk-1/Erk-2 activity but, instead, was found to depend on Ca2+
      influx. Taken together, these results indicate that hypotonic stress induces Erk
      1/Erk-2 activation through the Ras/Raf-signalling pathway, and argue against a
      direct role for this pathway in cell-volume control.

PMID- 9560316
TI  - Cloning and expression of a cDNA encoding a new neurocalcin isoform (neurocalcin
      alpha) from bovine brain.
AB  - Neurocalcin (NC), a neuron-specific EF-hand Ca2+-binding protein, purified from
      bovine brain [Terasawa, Nakano, Kobayashi and Hidaka (1992) J. Biol. Chem. 267,
      19596-19599] contains multiple isoforms. We previously cloned NCdelta from bovine
      brain and showed high expression in neuronal tissues [Okazaki, Watanabe, Ando,
      Hagiwara, Terasawa and Hidaka (1992) Biochem. Biophys. Res. Commun. 185, 147
      153]. We report here the molecular cloning and expression of a cDNA encoding
      bovine brain NCalpha. The translated bovine protein is 191 amino acids long and
      shares 69.1% of its amino acid sequence with NCdelta. Recombinant NCalpha
      migrates as a single 23 kDa band and exhibits a Ca2+-dependent mobility shift on
      SDS/PAGE. Analysis of fluorescence emission spectra showed the Ca2+-induced peak
      at 337 nm. Interestingly, the mobility shift and the fluorescence intensity at
      337 nm were larger for NCalpha than for NCdelta. In Ca2+-overlay experiments,
      however, the apparent affinity of NCalpha for 45Ca2+ was similar to that of
      NCdelta. Immunohistochemical analysis revealed NCalpha expression in the granular
      layer of the rat cerebellar cortex whereas NCdelta was found in the Purkinje cell
      layer. In the rat olfactory bulb, NCalpha was located in external tufted cells,
      and NCdelta was found in the periglomerular cells. These data demonstrate that NC
      isoforms differ in their tissue distribution and conformational changes induced
      by Ca2+ binding. Thus differential regulation of the two NC isoforms may be
      involved in control of neuron function.

PMID- 9560317
TI  - Metabolic control analysis of the bc1 complex of Saccharomyces cerevisiae: effect
      on cytochrome c oxidase, respiration and growth rate.
AB  - A number of strains varying in steady-state level of assembled bc1 complex were
      used to test the conclusions from inhibitor titration experiments with isolated
      mitochondria that, in cells of Saccharomyces cerevisiae grown on non-fermentable
      carbon sources, the control coefficient of the bc1 complex on the mitochondrial
      respiratory capacity equals 1 and the respiratory chain consists of
      supermolecular respiratory units [Boumans, Grivell and Berden (1998) J. Biol.
      Chem. 273, 4872-4877]. In addition, the control coefficient of mitochondrial
      respiration on the growth rate was determined. It was found that a reduced level
      of bc1 complex is accompanied by an almost parallel decrease in steady-state
      level of cytochrome c oxidase. Since the linear relationship between level of
      active bc1 complex and respiratory capacity still holds, it is concluded that
      cytochrome c oxidase has disappeared from respiratory units that are already
      deficient in the bc1 complex and that the cytochrome c oxidase in a respiratory
      unit is destabilized when the bc1 complex is deficient. The control coefficient
      of the bc1 complex, and thus of mitochondrial electron-transfer capacity, on
      respiration of intact cells (without uncoupler added) is 0.20. Addition of
      uncoupler results in an increase in the coefficient to 0.36. Thus changing the
      respiratory state changes the distribution of control, increasing the control
      coefficient of electron-transfer activity as the respiratory state goes towards
      State 3u. Rates of growth of the strains on different carbon sources were
      determined and subsequently fitted to calculate control coefficients of the bc1
      complex (and therefore of the respiratory capacity) on growth. Little variation
      was found between lactate-, ethanol- and glycerol-containing media, control
      coefficients being around 0.18 at pH 5. At pH 7 the control coefficient increased
      to 0.57, indicative of a higher dependence of the cell on ATP derived from
      oxidative phosphorylation. During growth on glucose-containing medium, the bc1
      complex has no control on the growth rate, as indicated by the fact that all
      strains, including a respiratory-deficient strain, grow as fast as the wild-type.
      However, the presence of respiratory capacity in the wild-type does result in a
      higher growth yield compared with the respiratory-deficient strain, indicating
      that, in contrast with what is generally assumed, in S. cerevisiae the 'Pasteur
      effect' is not restricted to special experimental conditions.

PMID- 9560318
TI  - LIM domains of cysteine-rich protein 1 (CRP1) are essential for its zyxin-binding
      function.
AB  - Previous studies have demonstrated that the adhesion-plaque protein, zyxin,
      interacts specifically with a 23 kDa protein, called the cysteine-rich protein 1
      (CRP1), which has been implicated in myogenesis. Primary sequence analyses have
      revealed that both zyxin and CRP1 exhibit multiple copies of a structural motif
      called the LIM domain. LIM domains, which are defined by the consensus CX2CX16
      23HX2CX2CX2CX16-23CX2-3(C,H,D), are found in a variety of proteins that are
      involved in cell growth and differentiation. Recent studies have established that
      LIM domains are zinc-binding structures that mediate specific protein-protein
      interactions. For example, in the case of the zyxin-CRP1 interaction, one of
      zyxin's three LIM domains is necessary and sufficient for binding to CRP1.
      Because the CRP1 molecule is comprised primarily of two LIM domains, we were
      interested in the possibility that the binding site for zyxin on CRP1 might also
      be contained within a single LIM domain. Consistent with the hypothesis that the
      LIM domains of CRP1 are critical for the protein's zyxin-binding function, zinc
      depleted CRP1 displays a reduced zyxin-binding activity. However, domain mapping
      analyses have revealed that neither of the two individual LIM domains of CRP1 can
      support a wild-type interaction with zyxin. Collectively, our results suggest
      that the binding site for zyxin on CRP1 is not contained within a single
      contiguous sequence of amino acids. Instead, the interaction appears to rely on
      the co-ordinate action of a number of residues that are displayed in both of
      CRP1's LIM domains.

PMID- 9560319
TI  - Alanine-261 in intracellular loop III of the human gonadotropin-releasing hormone
      receptor is crucial for G-protein coupling and receptor internalization.
AB  - Gonadotropin-releasing hormone (GnRH) is a decapeptide that regulates
      reproductive function via binding to the GnRH receptor, which is a G-protein
      coupled receptor (GPCR). For several members of this family, the C-terminal
      domain of intracellular loop III is important in ligand-mediated coupling to G
      proteins; mutations in that region can lead to constitutive activity. A specific
      alanine residue is involved in certain GPCRs, the equivalent of which is Ala-261
      in the GnRH receptor. Mutation of this residue to Leu, Ile, Lys, Glu or Phe in
      the human GnRH receptor did not result in constitutive activity and instead led
      to complete uncoupling of the receptor (failure to support GnRH-stimulated
      inositol phosphate production). When this residue was mutated to Gly, Pro, Ser or
      Val, inositol phosphate production was still supported. All the mutants retained
      the ability to bind ligand, and the affinity for ligand, where measured, was
      unchanged. These results show that Ala-261 cannot be involved in ligand binding
      but is critical for coupling of the receptor to its cognate G-protein. Coupling
      is also dependent on the size of the residue in position 261. When the amino acid
      side chain has a molecular mass of less than 40 Da efficient coupling is still
      possible, but when its molecular mass exceeds 50 Da the receptor is uncoupled.
      Internalization studies on the Ala261-->Lys mutant showed a marked decrease in
      receptor internalization compared with the wild type, indicating that coupling is
      necessary for effective receptor internalization in the GnRH receptor system.
      Activation of protein kinase C (with PMA), but not protein kinase A (with
      forskolin) markedly increased the internalization of the mutant receptor while
      having a small effect on the wild-type receptor.

PMID- 9560320
TI  - Periplasmic nitrate-reducing system of the phototrophic bacterium Rhodobacter
      sphaeroides DSM 158: transcriptional and mutational analysis of the napKEFDABC
      gene cluster.
AB  - The phototrophic bacterium Rhodobacter sphaeroides DSM 158 is able to reduce
      nitrate to nitrite by means of a periplasmic nitrate reductase which is induced
      by nitrate and is not repressed by ammonium or oxygen. Recently, a 6.8 kb PstI
      DNA fragment carrying the napABC genes coding for this periplasmic nitrate
      reducing system was cloned [Reyes, Roldan, Klipp, Castillo and Moreno-Vivian
      (1996) Mol. Microbiol. 19, 1307-1318]. Further sequence and genetic analyses of
      the DNA region upstream from the napABC genes reveal the presence of four
      additional nap genes. All these R. sphaeroides genes seem to be organized into a
      napKEFDABC transcriptional unit. In addition, a partial open reading frame
      similar to the Azorhizobium caulinodans yntC gene and the Escherichia coli yjcC
      and yhjK genes is present upstream from this nap gene cluster. The R. sphaeroides
      napK gene codes for a putative 6.3 kDa transmembrane protein which is not similar
      to known proteins and the napE gene codes for a 6.7 kDa transmembrane protein
      similar to the Thiosphaera pantotropha NapE. The R. sphaeroides napF gene product
      is a 16.4 kDa protein with four cysteine clusters that probably bind four [4Fe
      4S] centres. This iron-sulphur protein shows similarity to the NapF and NapG
      proteins of E. coli and Haemophilus influenzae. Finally, the napD gene product is
      a 9.4 kDa soluble protein which is also found in E. coli and T. pantotropha. The
      5' end of the nap transcript has been determined by primer extension, and a
      sigma70-like promoter has been identified upstream from the napK gene. The same
      transcriptional start site is found for cells growing aerobically or
      anaerobically with nitrate. Different mutant strains carrying defined polar and
      non-polar insertions in each nap gene were constructed. Characterization of these
      mutant strains demonstrates the participation of the nap gene products in the
      periplasmic nitrate reduction in R. sphaeroides.

PMID- 9560321
TI  - Interaction of macrophage-migration-inhibitory factor with haematin.
AB  - Macrophage-migration-inhibitory factor (MIF) is retained by S-hexylglutathione
      agarose but is not specifically eluted in high yield. Human liver MIF was
      purified in high yield using retention by phenyl-agarose at low ionic strength
      and cation-exchange FPLC as described for bovine lens MIF [Rosengren, Bucala,
      Aman, Jacobsson, Odh, Metz and Rorsman (1996) Mol. Med. 2, 143-149]. The l
      dopachrome methyl ester tautomerase activity of human liver MIF was not inhibited
      by a variety of glutathione S-conjugates, eicosanoids or glucocorticoids but was
      very sensitive to inhibition by haematin (IC50 100-200 nM). The inhibition was
      non-competitive and showed positive co-operativity (h=5.8). Similar sensitivity
      to haematin was obtained with purified recombinant human MIF. The sensitivity of
      MIF to haematin is approx. 1000-fold greater than for any previously described
      ligands, and is within its physiological range. Therefore the interaction is
      likely to be important in modulating the function of MIF in the initiation of
      immune responses.

PMID- 9560322
TI  - Synergistic transcriptional activation of the mouse urokinase plasminogen
      activator (uPA) gene and of its enhancer activator protein 1 (AP1) site by cAMP
      and retinoic acid.
AB  - We have investigated the mechanism whereby all-trans retinoic acid (tRA)
      potentiates the 8-bromo-cAMP (8-BrcAMP)-dependent transcription of the urokinase
      plasminogen activator (uPA) gene in SC115 mouse mammary carcinoma cells.
      Photoaffinity labelling experiments showed that tRA did not alter the cellular
      content of cAMP-dependent protein kinase regulatory subunits I and II. In
      agreement with this, nuclear run-on analysis in the presence of the translational
      inhibitor puromycin demonstrated that the effect of 8-BrcAMP and its potentiation
      by tRA were independent of protein synthesis. A transiently transfected 6.6 kb
      uPA 5'-flanking region-chloramphenicol acetyltransferase (CAT) fusion gene
      mimicked the response of the endogenous uPA gene. Thus 1 mM 8-BrcAMP induced a
      100-200% increase in CAT content, 100 nM tRA had no effect and 100 nM tRA+1 mM 8
      BrcAMP induced a 300-500% increase in cells co-transfected with tRA receptor
      and/or 9-cis-RA receptor. Analysis of 5'-deleted constructs showed that the tRA
      effect required at least two cis regions: -2657 to -2186, encompassing the 100 bp
      uPA enhancer, and -709 to -324, which exhibited silencing activity. Neither
      region contained a tRA-response element-like motif. Because tRA receptor and 9
      cis-RA receptor interact with activator protein 1 (AP1), we tested whether tRA
      regulated the uPA enhancer AP1 site in the presence of 8-BrcAMP. We found that a
      dimer of this site fused to a minimal uPA-CAT fusion gene was responsive to 1 mM
      8-BrcAMP (100% CAT increase), not responsive to 100 nM tRA, and synergistically
      responsive to 100 nM tRA+1 mM 8-BrcAMP (240% CAT increase) in cells co
      transfected with Fos and Jun. Synergistic activation of the same construct and of
      the 6.6 kb uPA-CAT fusion gene was also obtained using tRA and 100 nM PMA. We
      conclude that multiple cis elements, probably including the uPA enhancer AP1
      site, mediate the tRA potentiation of uPA transcription.

PMID- 9560324
TI  - Protein heterogeneity of spinach pullulanase results from the coexistence of
      interconvertible isomeric forms of the monomeric enzyme.
AB  - Purified pullulanase (starch-debranching enzyme, R-enzyme, EC 3.2.1. 41) from
      spinach (Spinacia oleracea L.) chloroplasts separated into at least seven
      individual enzymically active proteins (isomers, numbered 1-7) on isoelectric
      focusing or column chromatofocusing. At their isoelectric points (between pH 4.7
      and 5.2) these forms were rather stable. At slightly alkaline pH, each converted
      into the whole set of isomers. PAGE of the purified enzyme under denaturing or
      non-denaturing conditions resulted in one protein band. When substrate
      (amylopectin or pullulan) was included in the gel, the native enzyme as well as
      any of the individual isomers separated into two (sometimes three) bands
      ('substrate-induced forms', numbered I-III) with different specific activities,
      dissociation constants of the enzyme-substrate complexes and activation energies.
      Each substrate-induced form produced the whole set of seven isomers on
      isoelectric focusing. The specific activity of the total enzyme reflected the
      relative proportions of the substrate-induced forms. To some extent the relative
      proportions, as determined by crossed immunoelectrophoresis, could be shifted in
      favour of the more or the less active forms by reduction with dithiothreitol, and
      gentle oxidation respectively. Activation by dithiothreitol did not alter the
      mode of action of the enzyme but only increased the velocity of substrate
      degradation and extended its activity into the pH range of the chloroplast. As a
      consequence of isomer interconversion, microheterogeneity could serve to regulate
      pullulanase activity in a biochemical manner that shares some features with
      allosteric regulation.

PMID- 9560325
TI  - cDNA sequence and heterologous expression of monomeric spinach pullulanase:
      multiple isomeric forms arise from the same polypeptide.
AB  - The spinach pullulanase gene was cloned and sequenced using peptide sequences of
      the purified enzyme as a starting point and employing PCR techniques and cDNA
      library screening. Its open reading frame codes for a protein of 964 amino acids
      which represents a precursor of the pullulanase. The N-terminal transit peptide
      consists of 65 amino acids, and the mature protein, comprising 899 amino acids,
      has a calculated molecular mass of 99kDa. Pullulanase is a member of the alpha
      amylase family. In addition to a characteristic catalytic (beta/alpha)8-barrel
      domain, it contains a domain, F, that is specific for branching and debranching
      enzymes. Pullulanase cDNA was expressed in Escherichia coli, and the purified
      protein was compared with the enzyme from spinach leaves. Identity of the two
      proteins was confirmed in terms of catalytic properties, N-terminal amino acid
      sequences and molecular masses. The pullulanase produced by E. coli showed the
      same microheterogeneity as the spinach leaf enzyme: it could be resolved into two
      substrate-induced forms by electrophoresis in amylopectin-containing
      polyacrylamide gels, and, in the absence of substrate, into several free forms
      (charge isomers) by isoelectric focusing or chromatofocusing. Rechromatofocusing
      of single free forms resulted in the originally observed pattern of molecular
      forms. However, heterogeneity of the protein disappeared on isoelectric focusing
      under completely denaturing conditions when only one protein band was observed.
      Post-translational modifications such as glycosylation and phosphorylation could
      be excluded as potential explanations for the protein heterogeneity. Therefore
      the microheterogeneity of spinach leaf pullulanase results from neither genetic
      variation nor post-translational modifications, but is a property of the single
      unmodified gene product. The different interconvertible forms of the pullulanase
      represent protein populations of different tertiary structure of the same
      polypeptide.

PMID- 9560323
TI  - Actin filaments participate in the relocalization of phosphatidylinositol3-kinase
      to glucose transporter-containing compartments and in the stimulation of glucose
      uptake in 3T3-L1 adipocytes.
AB  - Insulin stimulates the rate of glucose uptake into muscle and adipose cells by
      translocation of glucose transporters from an intracellular storage pool to the
      plasma membrane. This event requires the prior activation of phosphatidylinositol
      3-kinase (PI 3-kinase). Here we report that insulin causes an increase in
      wortmannin-sensitive PI 3-kinase activity and a gain in the enzyme's regulatory
      and catalytic subunits p85alpha and p110beta (but not p110alpha) in the
      intracellular compartments containing glucose transporters. The hormone also
      caused a marked reorganization of actin filaments, which was prevented by
      cytochalasin D. Cytochalasin D also decreased significantly the insulin-dependent
      association of PI 3-kinase activity and the levels of insulin receptor substrate
      (IRS)-1, p85alpha and p110beta with immunopurified GLUT4-containing compartments.
      In contrast, the drug did not alter the insulin-induced tyrosine phosphorylation
      of IRS-1, the association of PI 3-kinase with IRS-1, or the stimulation of PI 3
      kinase by insulin in anti-(IRS-1) or anti-p85 immunoprecipitates from whole cell
      lysates. Cytochalasin D, and the chemically unrelated latrunculin B, which also
      inhibits actin filament reassembly, prevented the insulin stimulation of glucose
      transport by approx. 50%. Cytochalasin D decreased by about one-half the insulin
      dependent translocation to the plasma membrane of the GLUT1 and GLUT4 glucose
      transporters. The results suggest that the existence of intact actin filament is
      correlated with the full recruitment of glucose transporters by insulin. The
      underlying function of the actin filaments might be to facilitate the insulin
      mediated association of the p85-p110 PI 3-kinase with glucose-transporter
      containing compartments.

PMID- 9560327
TI  - Molecular cloning and expression of a cDNA encoding an olfactory-specific mouse
      phenol sulphotransferase.
AB  - Previously we demonstrated the presence of phenol sulphotransferase (P-ST) in
      mouse nasal cytosols and identified its zonal location in mouse nasal cavity by
      staining with an antiserum raised against a rat liver P-ST isoenzyme, PSTg. In
      the present study a cDNA was isolated from a mouse olfactory cDNA library by
      immunological screening with the antiserum. The isolated cDNA consisted of 1347
      bp with a 912 bp open reading frame encoding a 304-residue polypeptide. Both the
      nucleotide and deduced amino acid sequences of the cDNA were 94% identical with
      those of a rat liver P-ST isoenzyme, ST1C1. The expressed enzyme in Escherichia
      coli displayed high P-ST activity towards phenolic odorants such as eugenol and
      guaiacol, and it showed a high N-hydroxy-2-acetylaminofluorene sulphation
      activity in comparison with the rat ST1C1 enzyme. These results indicate that the
      olfactory P-ST encoded by the cDNA is a mouse orthologue of rat ST1C1; however,
      expression of the olfactory P-ST mRNA is specific for nasal tissues as revealed
      by reverse transcriptase-mediated PCR (RT-PCR).

PMID- 9560326
TI  - Modulation of Ins(2,4,5)P3-stimulated Ca2+ mobilization by ins(1,3,4, 5)P4:
      enhancement by activated G-proteins, and evidence for the involvement of a GAP1
      protein, a putative Ins(1,3,4,5)P4 receptor.
AB  - We have previously shown that addition of Ins(1,3,4,5)P4 to permeabilized L1210
      cells increases the amount of Ca2+ mobilized by a submaximal concentration of
      Ins(2,4,5)P3, and we suggested that, in doing this, Ins(1,3,4,5)P4 is not working
      via an InsP3 receptor but indirectly via an InsP4 receptor [Loomis-Husselbee,
      Cullen, Dreikhausen, Irvine and Dawson (1996) Biochem. J. 314, 811-816]. Here we
      have investigated whether this effect might be mediated by GAP1(IP4BP), recently
      identified as a putative receptor for Ins(1,3, 4,5)P4. GAP1(IP4BP) is a protein
      that interacts with one or more monomeric G-proteins, so we sought evidence for
      involvement of monomeric G-proteins in the effects of Ins(1,3,4,5)P4 in
      permeabilized L1210 cells. Guanosine 5'-[gamma-thio]triphosphate (GTP[S])
      enhanced the effect of Ins(1,3,4,5)P4 on Ins(2,4, 5)P3-stimulated Ca2+
      mobilization, but had no effect on the action of Ins(2,4,5)P3 alone. A specific
      enhancement of only the action of Ins(1,3,4,5)P4 was also seen with GTP[S]-loaded
      R-Ras or Rap1a (two G-proteins known to interact with GAP1(IP4BP)), whereas H-Ras
      was inactive at similar concentrations. Guanosine 5'-[beta-thio]diphosphate
      (GDP[S]) did not alter the action of either Ins(2,4,5)P3 or Ins(1,3,4,5)P4.
      Finally, the addition of exogenous GAP1(IP4BP), purified from platelets, markedly
      enhanced the effect of Ins(1,3,4,5)P4, and again, the amount of Ca2+ mobilized by
      Ins(2,4,5)P3 alone was unaltered. We conclude that the increase in Ins(2,4,5)P3
      stimulated Ca2+ mobilization by Ins(1,3,4, 5)P4 may be mediated by GAP1(IP4BP) or
      a closely related protein (such as GAP1(m)), and if so, the action of the GAP1 is
      not solely to regulate GTP loading of a G-protein, but rather it acts with a G
      protein to cause its effect.

PMID- 9560328
TI  - The gene structure and organization of mouse PG-Lb, a small chondroitin/dermatan
      sulphate proteoglycan.
AB  - PG-Lb was originally characterized as a small chondroitin/dermatan sulphate
      proteoglycan expressed preferentially in the zones of flattened chondrocytes in
      developing chick limb cartilage. The occurrence of this proteoglycan in mammalian
      cartilage has been shown by the isolation of a cDNA clone from mouse cartilage
      cDNA library [Kurita, Shinomura,Ujita, Zako, Kida, Iwata and Kimata (1996)
      Biochem. J. 318, 909-914]. To understand the regulation mechanisms for such a
      unique expression, we have investigated a genomic DNA structure of the PG-Lb
      gene. The gene is composed of seven exons and six introns spanning more than 50
      kb. The leucine-rich repeats are encoded from exon V to exon VII. The
      transcription initiation site has been determined by rapid amplification of the
      cDNA ends ('5'-RACE'). The possible TATA box was detected about 90 bp upstream of
      the adenosine residue that was numbered as position +1. Further analyses of 1.5
      kb of the 5' flanking region and 2.2 kb of the first intron have revealed several
      potential binding motifs for transcription factors such as Sox 5 and 9. The
      presence of those sequences in the PG-Lb gene was discussed in relation to the
      unique expression of this proteoglycan. The chromosomal localization of the
      murine PG-Lb gene was determined to be on the mouse chromosome 10 by the
      fluorescence-in-situ-hybridization ('FISH') method.

PMID- 9560330
TI  - Visual memory: what do you know about what you saw?
AB  - Recent studies of visual perception are bringing us closer to an understanding of
      what we remember - and what we forget - when we recall a scene.

PMID- 9560331
TI  - Face processing: getting by with a little help from its friends.
AB  - Functional imaging identified a putative face-specific area within the fusiform
      gyrus of human visual cortex; the precise role of this area is still in question,
      however, and recent imaging studies have implicated other cortical areas in face
      processing. These studies show the dangers of considering a single cortical area
      in isolation.

PMID- 9560329
TI  - Activation of gelatinase-tissue-inhibitors-of-metalloproteinase complexes by
      matrilysin.
AB  - Matrilysin, gelatinase A and gelatinase B are matrix metalloproteinases (MMPs)
      implicated in normal and pathological processes that require remodelling of the
      extracellular matrix. In human prostate tissue, matrilysin is synthesized in
      ducts surrounded by inflammatory cells, and focally in prostate carcinoma, but
      not in normal glands. Gelatinase B expression is restricted to inflammatory
      cells. Gelatinase A can be found in both benign and malignant prostate tissue.
      MMP activities are regulated by their transition from latent to activated forms,
      as well as by the presence of tissue inhibitors of metalloproteinases (TIMPs). We
      investigated whether matrilysin can activate progelatinases A and B in the
      presence of their bound inhibitors TIMP2 and TIMP1 respectively. Incubation of
      progelatinase B-TIMP1 complex with active matrilysin resulted in 78 and 68 kDa
      active forms, as measured by SDS-PAGE and enzyme activity assays. TIMP-free
      gelatinase B was also activated by matrilysin. In addition, activation of
      progelatinase B by matrilysin was demonstrated in the conditioned medium of
      phorbol ester-treated HT1080 cells, confirming the results obtained in the in
      vitro experiments. In contrast, matrilysin did not proteolytically cleave
      gelatinase A-TIMP2 complex, but led to a transient increase in gelatinolytic
      activity of the proenzyme. Matrilysin did not enhance the autocatalytic
      conversion of its own proform. The data presented here suggest that matrilysin
      participates in a proteolytic cascade and can activate gelatinases in the
      presence of TIMPs.

PMID- 9560332
TI  - Cell nucleus: chromosome dynamics in nuclei of living cells.
AB  - Unraveling chromosome movements in vivo is indispensable for understanding the
      functional architecture of the nucleus and its relationship to the functional
      state of the cell. New experimental approaches have now made it possible to
      monitor chromosome dynamics within the nuclei of living cells.

PMID- 9560333
TI  - Neuronal regeneration: extending axons from bench to brain.
AB  - Many studies have shown that myelin in the central nervous system strongly
      inhibits the regeneration of axons, so it comes as a surprise to discover that
      adult neurons transplanted into the brain rapidly extend their axons through
      myelinated pathways.

PMID- 9560334
TI  - G-protein signaling: fine-tuning signaling kinetics.
AB  - Mammalian 'regulators of G protein signaling' (RGS proteins) help shut off G
      protein-mediated signaling by GTPase activation. But new evidence shows that RGS
      proteins can also speed up the activation of signaling. The combined effect is a
      change in signaling kinetics without a decrease in signaling intensity.

PMID- 9560335
TI  - Peroxisome biogenesis: back to the endoplasmic reticulum?
AB  - Proteins are targeted to the membrane and matrix of peroxisomes by distinct
      pathways. Recent observations suggest a further route: a subset of peroxisomal
      membrane proteins might be targeted first to the endoplasmic reticulum, and from
      there to peroxisomes by vesicle-mediated transport.

PMID- 9560336
TI  - Protein folding: think globally, (inter)act locally.
AB  - Protein folding appears to be almost too complex for a complete description or
      for accurate structure prediction from sequence data. A simple way of analysing
      local interactions, however, bears promise of linking theory with experiment and
      cutting through some of the complexities.

PMID- 9560337
TI  - Auxin signalling: protein stability as a versatile control target.
AB  - Two components of an auxin signalling pathway in Arabidopsis have been found to
      be homologous to budding yeast enzymes that are known to be involved in
      regulating the stability of key cell-cycle regulatory proteins, such as the
      cyclin-dependent kinase inhibitor Sic1p.

PMID- 9560338
TI  - The malignant capacity of skin tumours induced by expression of a mutant H-ras
      transgene depends on the cell type targeted.
AB  - BACKGROUND: . Pinpointing the cells from which tumours arise is a major challenge
      n tumour biology. Previous work has shown that the targeted expression of a
      mutant ras gene within the interfollicular cell compartment of mouse skin induces
      the formation of benign papillomas, but these do not spontaneously progress to
      malignancy. We have investigated the carcinogenic effects of expressing the same
      oncogene in a different population of epidermal cells. RESULTS: Expression of
      mutant ras from a truncated keratin 5 gene promoter, which directs expression to
      the follicular and interfollicular cells of newborn mice and the hair follicle
      cells of adults, stimulated the development of acanthotic areas in newborn mice.
      Within one week of birth, the acanthotic skin developed areas of carcinoma in
      situ and adult mice developed papillomas and keratoacanthomas, the latter having
      a high frequency of spontaneous malignant transformation to squamous and
      occasionally spindle carcinomas. The benign tumours that arose had several
      hallmarks of tumours at a high risk of malignant progression, including
      suprabasal cell proliferation and heterogeneous expression of keratin 13. In
      contrast to tumours induced by expressing mutant ras under the control of the
      keratin 10 or keratin 1 gene promoters, the formation of these lesions was not
      dependent on wounding or a tumour promoter. CONCLUSIONS: Benign tumours that are
      at a risk of malignant conversion are primarily derived from cells located within
      the hair follicle, and the nature of the cell in which tumour initiation occurs
      is a major determinant of malignant potential.

PMID- 9560339
TI  - Helios, a novel dimerization partner of Ikaros expressed in the earliest
      hematopoietic progenitors.
AB  - BACKGROUND: Normal hematopoietic development depends on the activity of the
      Ikaros transcription factor, which contains distinct zinc-finger domains that
      mediate DNA binding and protein dimerization. Mice homozygous for a transgene
      encoding a dominant-negative version of Ikaros that lacks the DNA-binding domain
      but not the dimerization domain have a more severe phenotype than Ikaros null
      mice. This observation suggests the presence of factor(s) that can dimerize with
      Ikaros and partially complement its function. One previously identified factor,
      Aiolos, probably serves this role in the lymphoid system; a related factor
      involved in hematopoietic progenitors remains unknown, however. RESULTS: Here, we
      describe the cloning of an Ikaros-related gene, Helios. Analysis of the primary
      sequences of Helios, Ikaros and Aiolos revealed that the DNA-binding,
      transcriptional activation and dimerization domains are functionally conserved.
      Helios activated transcription from Ikaros DNA-binding sites and could dimerize
      with itself, Ikaros or Aiolos. Expression of Helios was detected in the earliest
      hematopoietic sites of the embryo, in hematopoietic stem cells in the adult and
      was subsequently restricted to a subset of cells in the T cell lineage. Helios co
      localized with Ikaros and Aiolos proteins in macromolecular nuclear structures
      and formed stable complexes in vivo with the dominant-negative version of Ikaros.
      CONCLUSIONS: Distinct but overlapping expression patterns of members of the
      Ikaros gene family during hematopoiesis might result in the formation of
      different multimeric complexes that have specific roles in lineage progression.
      The preferential expression of Helios in the earliest stages of hematopoiesis
      suggests that this gene functions predominantly in early progenitors.

PMID- 9560340
TI  - The interaction of the cell-contact proteins VASP and vinculin is regulated by
      phosphatidylinositol-4,5-bisphosphate.
AB  - BACKGROUND: Focal adhesion sites are cell-matrix contacts that are regulated by
      phosphatidylinositol-4,5-bisphosphate (PIP2)-dependent pathways. Vinculin is a
      major structural component of these sites and is thought to be engaged in
      multiple ligand interactions at the cytoplasmic face of these contacts.
      Cytoplasmic vinculin is considered to be inactive due to its closed conformation
      involving intramolecular head-tail interactions. Recently, the vasodilator
      stimulated phosphoprotein (VASP), a substrate of cyclic AMP-dependent or cyclic
      GMP-dependent kinases and a component of focal adhesion sites, was shown to bind
      to vinculin. RESULTS: VASP-vinculin complexes could be immunoprecipitated from
      cell lysates and, using immunofluorescence, both proteins were found to
      colocalize in nascent focal adhesions. Consistent with the view that vinculin
      must be activated at these sites, we found that PIP2, levels of which are
      elevated during the early stages of adhesion, bound to two discrete regions in
      the vinculin tail, disrupting the intramolecular head-tail interaction and
      inducing vinculin oligomerization. Vinculin-VASP complex formation was greatly
      enhanced by PIP2 and both the EVH1 and EVH2 domains of VASP participated in
      vinculin binding. CONCLUSIONS: Focal contact assembly involves interaction
      between VASP and vinculin, which is enhanced by PIP2-induced vinculin activation
      and oligomerization. Given that vinculin and VASP both bind to F-actin, vinculin
      VASP complexes might bundle the distal ends of actin filaments in focal contacts.
      We propose that PIP2-dependent signalling modulates microfilament organization at
      cellular adhesion sites by regulating vinculin-VASP complexes.

PMID- 9560341
TI  - A highly conserved RNA-binding protein for cytoplasmic mRNA localization in
      vertebrates.
AB  - BACKGROUND: Cytoplasmic mRNA localization is a widespread mechanism for
      restricting the translation of specific mRNAs to distinct regions of eucaryotic
      cells. This process involves specific interactions between cellular factors and
      localization signals in the 3' untranslated regions of the localized mRNA.
      Because only a few of these cellular factors have been identified, it is not
      known whether common factors are utilized for the localization of different
      mRNAs. We recently discovered Vera, a protein that binds specifically to the Vg1
      localization element and is involved in the localization of Vg1 mRNA in Xenopus
      oocytes. RESULTS: To characterize further the role of Vera in the localization of
      Vg1 mRNA, we have purified the Vera protein and cloned its gene. Vera is
      homologous to chicken zip-code-binding protein (ZBP), which binds to a short RNA
      sequence required for localization of beta-actin mRNA in chick embryo
      fibroblasts. The predicted amino-acid sequences of Vera and ZBP contain five RNA
      binding domains and putative signals for nuclear localization and export. Like
      the binding of ZBP to beta-actin mRNA, Vera specifically binds to a repeated
      sequence motif in the Vg1 localization element that is required for Vg1 mRNA
      localization in Xenopus oocytes. CONCLUSIONS: Vera, a highly conserved component
      of the mRNA localization machinery, participates in localizing different mRNAs in
      different cell types. Thus, Vera appears to be a general factor for mRNA
      localization, and additional factors may be required to specify diverse patterns
      of RNA localization.

PMID- 9560342
TI  - The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin
      destruction machinery in S. cerevisiae.
AB  - BACKGROUND: Following chromosome segregation in anaphase, ubiquitin-dependent
      degradation of mitotic cyclins contributes to the exit from mitosis. A key step
      in this process is catalyzed by a ubiquitin-protein ligase known as the anaphase
      promoting complex (APC), the regulation of which is poorly understood. The Polo
      related protein kinase Cdc5 in Saccharomyces cerevisiae might encode a regulator
      of the APC, because cdc5 mutant cells arrest with a late mitotic phenotype
      similar to that observed in cells with defective cyclin destruction. RESULTS: We
      investigated the role of Cdc5 in the regulation of mitotic cyclin degradation. In
      cdc5-1 mutant cells, we observed a defect in the destruction of cyclins and a
      reduction in the cyclin-ubiquitin ligase activity of the APC. Overexpression of
      CDC5 resulted in increased APC activity and mitotic cyclin destruction in
      asynchronous cells or in cells arrested in metaphase. CDC5 mutation or
      overexpression did not affect the degradation of the APC substrate Pds 1, which
      is normally degraded at the metaphase-to-anaphase transition. Cyclin-specific APC
      activity in cells overexpressing CDC5 was reduced in the absence of the APC
      regulatory proteins Hct 1 and Cdc20. In G1, Cdc5 itself was degraded by an APC
      dependent and Hct1-dependent mechanism. CONCLUSIONS: We conclude that Cdc5 is a
      positive regulator of cyclin-specific APC activity in late mitosis. Degradation
      of Cdc5 in G1 might provide a feedback mechanism by which the APC destroys its
      activator at the onset of the next cell cycle.

PMID- 9560343
TI  - Identification of a ligand for the death-domain-containing receptor Apo3.
AB  - The tumor necrosis factor (TNF) cytokine family regulates development and
      function of the immune system [1]. TNF is expressed primarily by activated
      lymphocytes and macrophages and induces gene transcription or apoptosis in target
      cells [2,3]. We have identified a novel relative of TNF that binds to the
      recently discovered, death-domain-containing receptor called Apo3 [4] (also known
      as DR3, WSL-1, TRAMP or LARD [5-9]). The Apo3 ligand (Apo3L) is a 249 amino-acid,
      type II transmembrane protein. The extracellular sequence of Apo3L shows highest
      identity to that of TNF. We detected Apo3L mRNA in many human tissues and mapped
      its encoding gene to chromosome 17p13, near the p53 tumor-suppressor gene.
      Soluble Apo3L induced apoptosis and nuclear factor kappaB (NF-kappaB) activation
      in human cell lines. Caspase inhibitors blocked apoptosis induction by Apo3L, as
      did a dominant-negative mutant of the cell death adaptor protein Fas-associated
      death domain protein (FADD/MORT1), which is critical for apoptosis induction by
      TNF [3]. Dominant-negative mutants of several factors that play a key role in NF
      kappaB induction by TNF [10] inhibited NF-kappaB activation by Apo3L. Thus, Apo3L
      has overlapping signaling functions with TNF, but displays a much wider tissue
      distribution.

PMID- 9560344
TI  - Angiopoietin-1 induces sprouting angiogenesis in vitro.
AB  - Sprouting of new capillaries from pre-existing blood vessels is a hallmark of
      angiogenesis during embryonic development and solid tumor growth [1]. In addition
      to the vascular endothelial growth factor (VEGF) and its receptors, the Tie
      receptors and their newly identified ligands, the angiopoietins, have been
      implicated in the control of blood vessel formation [2,3]. Although 'knockouts'
      of the gene encoding the Tie2 receptor, or its activating ligand angiopoietin-1
      (Ang1), result in embryonic lethality in mice due to an absence of remodeling and
      sprouting of blood vessels [4,5], biological activity in vitro has not yet been
      described for this receptor-ligand system. In an assay in which a monolayer of
      endothelial cells were cultured on microcarrier beads and embedded in three
      dimensional fibrin gels, recombinant Ang1 (0.5-10 nM) induced the formation of
      capillary sprouts in a dose-dependent manner that was completely inhibited by
      soluble Tie2 receptor extracellular domains. In contrast with VEGF, which also
      induced sprouting of capillaries, Ang1 was only very weakly mitogenic for
      endothelial cells. Suboptimal concentrations of VEGF and Ang1 acted
      synergistically to induce sprout formation. Thus, the biological activity of Ang1
      in vitro is consistent with the specific phenotype of mice deficient in Tie2 or
      Ang1. The data suggest that, like in other developmental systems, blood vessel
      formation requires a hierarchy of master-control genes in which VEGF and
      angiopoietins, along with their receptors, are amongst the most important
      regulators.

PMID- 9560345
TI  - The globular domain of histone H1 is sufficient to direct specific gene
      repression in early Xenopus embryos.
AB  - One molecule of a linker histone such as histone H1 is incorporated into every
      metazoan nucleosome [1]. Histone H1 has three distinct structural domains: the
      positively charged amino-terminal and carboxy-terminal tails are separated by a
      globular domain that is similar to the winged-helix motif found in sequence
      specific DNA-binding proteins [2]. The globular domain interacts with DNA
      immediately contiguous to that wrapped around the core histones [3,4], whereas
      the tail domains are important for the compaction of nucleosomal arrays [5].
      Experiments in vivo indicate that histone H1 does not function as a global
      transcriptional repressor, but instead has more specific regulatory roles [6-9].
      In Xenopus, maternal stores of the B4 linker histone that are assembled into
      chromatin during the early cleavage divisions are replaced by somatic histone H1
      during gastrulation [10]. This transition in chromatin composition causes the
      repression of genes encoding oocyte-type 5S rRNAs, and restricts the competence
      of ectodermal cells to differentiate into mesoderm [6,9-11]. Here, we demonstrate
      that the globular domain of histone H1 is sufficient for directing gene-specific
      transcriptional repression and for restricting the mesodermal competence of
      embryonic ectoderm. We discuss our results in the context of specific structural
      roles for this domain in the nucleosome.

PMID- 9560346
TI  - CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45.
AB  - Induction of apoptosis by death receptors such as Fas or tumour necrosis factor
      (TNF) R1 leads to distinct changes in cell morphology, activation of the caspase
      protease cascade, and the degradation of nuclear chromatin by activated
      nucleases. Here, we describe the purification and cDNA cloning of a novel 40 kDa
      endonuclease from Jurkat cells that is activated by caspases. This protein,
      designated caspase-activated nuclease (CPAN), is sufficient to degrade naked DNA
      and to induce apoptotic morphology and DNA fragmentation in naive nuclei. CPAN is
      highly homologous to a recently described mouse nuclease, CAD [1], and may
      represent the human homologue. Our data on the human cDNA as well as additional
      data on the mouse homologue suggest that a 30 amino-acid portion of the recently
      published mouse sequence [1] is incorrect. We show that the activity of human
      CPAN is regulated by DFF45 [2], an inhibitor necessary for CPAN expression and
      stabilization in an inactive state in living cells. Proteolytic cleavage of DFF45
      by caspases in vitro leads to dissociation of DFF45 fragments from CPAN and
      activation of CPAN as an endonuclease. CPAN is a tightly regulated endonuclease
      with unique characteristics that might represent a distinctive family of
      endonucleases.

PMID- 9560347
TI  - Dynein and dynactin are localized to astral microtubules and at cortical sites in
      mitotic epithelial cells.
AB  - The mitotic spindle is often positioned in a characteristic location during
      development, for example to enable the proper segregation of developmental
      determinants [1,2]. When epithelial cells divide, the mitotic spindle is often
      positioned parallel to the plane of the epithelium, so that both daughter cells
      contribute to the epithelium [3]. The mechanisms by which mitotic spindles are
      positioned have not been characterized in great detail, but evidence is
      accumulating that in some systems the dynein-dynactin microtubule motor complex
      plays a role [4-6]. Dynein has yet not been localized to cortical sites where it
      could bind to microtubules and exert a force that might orient the mitotic
      spindle, however [7,8]. Here, we report that in mitotic polarized epithelial
      cells, the dynein-dynactin complex accumulates, from prometaphase onwards, along
      astral microtubules and at cortical spots, into which many of the astral
      microtubules dock. The spots are assembled at the lateral plasma membrane, in the
      region below the tight junctions. Their formation is inhibited by cytochalasin D,
      and under these conditions the spindles do not orient properly. This novel
      localization of the dynein-dynactin complex is consistent with a role for the
      complex in the positioning of the mitotic spindle. We also show that, during
      prophase, the motor complex colocalizes with the nuclear envelope, consistent
      with it having a role in separating the centrosomes that are associated with the
      nuclear envelope.

PMID- 9560348
TI  - Following comets 

PMID- 9560349
TI  - Sperm and scrambled eggs 

PMID- 9560350
TI  - Web sequence gazing 

PMID- 9560351
TI  - For yew and me 

PMID- 9560352
TI  - Tap water tempest 

PMID- 9560353
TI  - Of human bandage 

PMID- 9560354
TI  - Profiles of Great Lakes critical pollutants: a sentinel analysis of human blood
      and urine. The Great Lakes Consortium.
AB  - To determine the contaminants that should be studied further in the subsequent
      population-based study, a profile of Great Lakes (GL) sport fish contaminant
      residues were studied in human blood and urine specimens from 32 sport fish
      consumers from three Great Lakes: Lake Michigan (n = 10), Lake Huron (n = 11),
      and Lake Erie (n = 11). Serum was analyzed for 8 polychlorinated dioxin
      congeners, 10 polychlorinated furan congeners, 4 coplanar and 32 other
      polychlorinated biphenyl (PCB) congeners, and 11 persistent chlorinated
      pesticides. Whole blood was analyzed for mercury and lead. Urine samples were
      analyzed for 10 nonpersistent pesticides (or their metabolites) and 5 metals. One
      individual was excluded from statistical analysis because of an unusual exposure
      to selected analytes. Overall, the sample (n = 31) consumed, on average, 49 GL
      sport fish meals per year for a mean of 33 years. On average, the general
      population in the GL basin consume 6 meals of GL sport fish per year. The mean
      tissue levels of most persistent, bioaccumulative compounds also found in GL
      sport fish ranged from less than a twofold increase to that of PCB 126, which was
      eight times the selected background levels found in the general population. The
      overall mean total toxic equivalent for dioxins, furans, and coplanar PCBs were
      greater than selected background levels in the general population (dioxins, 1.8
      times; furans, 2.4 times; and coplanar PCBs, 9.6 times). The nonpersistent
      pesticides and most metals were not identified in unusual concentrations. A
      contaminant pattern among lake subgroups was evident. Lake Erie sport fish
      consumers had consistently lower contaminant concentrations than consumers of
      sport fish from Lake Michigan and Huron. These interlake differences are
      consistent with contaminant patterns seen in sport fish tissue from the
      respective lakes; GL sport fish consumption was the most likely explanation for
      observed contaminant levels among this sample. Frequent consumers of sport fish
      proved to be effective sentinels for identifying sport fish contaminants of
      concern. In the larger study to follow, serum samples will be tested for PCBs
      (congener specific and coplanar), DDE, dioxin, and furans.

PMID- 9560355
TI  - Indoor air quality and acute lower respiratory infection in Indian urban slums.
AB  - The present prospective study was conducted at two urban slums of Delhi, Kusumpur
      Pahari and Kathputly Colony, in the peak winter season from November 1994 through
      February 1995. We studied 642 infants to determine the incidence of acute lower
      respiratory infection (ALRI) and its relationship to indoor air pollution due to
      fuel used for cooking (wood or kerosene). In Kusumpur Pahari, there were 317
      children (142 wood and 175 kerosene), including 64 controls and 78 cases of ALRI
      in the wood fuel group and 81 controls and 94 ALRI cases in the kerosene group (p
      > 0.05). Out of 316 children in Kathputly Colony (174 wood and 142 kerosene),
      there were 33 and 45 ALRI cases in the wood and kerosene groups, respectively (p
      < 0.05). Controls were children without ALRI and were used as controls in
      different groups. The demographic data and risk factors, namely, nutritional and
      immunization status, were comparable in ALRI cases and controls in both study
      areas. Pneumonia was the most common ailment in all the groups. Bronchiolitis was
      reported in 22.5% of the wood group and 27.1% of the kerosene group in Kathputly
      Colony versus 13.7% in the wood group and 12.1% in the kerosene group in Kusumpur
      Colony. Only one case of croup was reported from Kusumpur Pahari among wood
      users. The duration of illness was longer in the Kusumpur Pahari due to poor
      compliance, feeding, and child rearing habits. In conclusion, a higher incidence
      of ALRI was reported in kerosene users in Kathputly Colony, a high pollution
      area; however, the reasons for the differences observed need further elucidation.

PMID- 9560356
TI  - No safe harbor.

PMID- 9560357
TI  - Tackling the big three.

PMID- 9560359
TI  - Testis-specific proteins and their role in contraceptive vaccine development.
AB  - Development of a vaccine(s) based on sperm antigens represents a promising
      approach for contraception. The utility of an antigen in immunocontraception is
      contingent upon its testis/sperm specificity and involvement in spermatogenesis
      and/or fertilization. The aim of the present article is to review the information
      regarding the proteins that have been reported to be testis/sperm-specific and
      may have an important function in spermatogenesis and/or fertilization. The
      potential role of these proteins in the development an antisperm contraceptive
      vaccine(s) is discussed.

PMID- 9560358
TI  - Cellular activation mechanisms in septic shock.
AB  - Septic shock is an increasingly important clinical condition, characterized by
      systemic hypotension, ischemia, and ultimately organ failure. In Gram negative
      infection, the bacterial cell wall component, lipopolysaccharide (endotoxin,
      LPS), has been strongly linked to the pathophysiological responses that result in
      septic shock. LPS is bound in plasma to a protein called LPS-binding protein
      (LBP), which facilitates the binding of LPS to a cell surface receptor, CD14.
      Binding to CD14 stimulates cell signaling mechanisms that result in the
      production of inflammatory cytokines. However, the events which follow LPS
      binding to CD14 and which lead to the production of cytokines remain unclear. It
      has recently become evident that a number of phosphorylation cascades including
      MAP kinase pathways and NF-kappaB activation pathway are initiated by exposure of
      cells to LPS. These cascades act at both the transcriptional and translational
      levels to regulate cytokine production. This review will focus on the signaling
      pathways that are initiated by LPS and the cellular effects of the signaling
      pathways.

PMID- 9560360
TI  - The Mom and Pop Editorial Shop.

PMID- 9560361
TI  - Young Jan.

PMID- 9560362
TI  - Some recollections and reflections on mutation rates.

PMID- 9560363
TI  - Mutation and cancer: the antecedents to our studies of adaptive mutation.

PMID- 9560364
TI  - The lacI gene as a target for mutation in transgenic rodents and Escherichia
      coli.
AB  - The lacI gene has been used extensively for the recovery and analysis of
      mutations in bacteria with various DNA repair backgrounds and after exposure to a
      wide variety of mutagens. This has resulted in a large database of information on
      mutational mechanisms and specificity of many mutagens, as well as the effect of
      DNA repair background on mutagenicity. Most importantly, knowledge about the
      mutational sensitivity of the lacI gene is now available, yielding information
      about mutable nucleotides. This popularity and available knowledge resulted in
      the use of the lacI gene in transgenic rodents for the study of mutagenesis in
      mammals, where it resides in approximately 40 repeated copies. As the number of
      sequenced mutations recovered from these animals increases, we are able to
      analyze the sites at which mutations have been recovered in great detail and to
      compare the recovered sites between bacteria and transgenic animals. The
      nucleotides that code for the DNA-binding domain are nearly saturated with base
      substitutions. Even after determining the sequences of approximately 10,000
      mutations recovered from the animals, however, new sites and new changes are
      still being recovered. In addition, we compare the nature of deletion mutations
      between bacteria and animals. Based on the nature of deletions in the animals, we
      conclude that each deletion occurs in a single copy of the gene.

PMID- 9560365
TI  - Adaptive mutation: has the unicorn landed?
AB  - Reversion of an episomal Lac- allele during lactose selection has been studied as
      a model for adaptive mutation. Although recent results show that the mutations
      that arise during selection are not "adaptive" in the original sense, the
      mutagenic mechanism that produces these mutations may nonetheless be of
      evolutionary significance. In addition, a transient mutational state induced in a
      subpopulation of starving cells could provide a species with a mechanism for
      adaptive evolution.

PMID- 9560366
TI  - A species barrier between bacteriophages T2 and T4: exclusion, join-copy and join
      cut-copy recombination and mutagenesis in the dCTPase genes.
AB  - Bacteriophage T2 alleles are excluded in crosses between T2 and T4 because of
      genetic isolation between these two virus species. The severity of exclusion
      varies in different genes, with gene 56, encoding an essential
      dCT(D)Pase/dUT(D)Pase of these phages, being most strongly affected. To
      investigate reasons for such strong exclusion, we have (1) sequenced the T2 gene
      56 and an adjacent region, (2) compared the sequence with the corresponding T4
      DNA, (3) constructed chimeric phages in which T2 and T4 sequences of this region
      are recombined, and (4) tested complementation, recombination, and exclusion with
      gene 56 cloned in a plasmid and in the chimeric phages in Escherichia coli CR63,
      in which growth of wild-type T2 is not restricted by T4. Our results argue
      against a role of the dCTPase protein in this exclusion and implicate instead DNA
      sequence differences as major contributors to the apparent species barrier. This
      sequence divergence exhibits a remarkable pattern: a major heterologous sequence
      counter-clockwise from gene 56 (and downstream of the gene 56 transcripts)
      replaces in T2 DNA the T4 gene 69. Gene 56 base sequences bordering this
      substituted region are significantly different, whereas sequences of the dam
      genes, adjacent in the clockwise direction, are similar in T2 and in T4. The gene
      56 sequence differences can best be explained by multiple compensating
      frameshifts and base substitutions, which result in T2 and T4 dCTPases whose
      amino acid sequences and functions remain similar. Based on these findings we
      propose a model for the evolution of multiple sequence differences concomitant
      with the substitution of an adjacent gene by foreign DNA: invasion by the single
      stranded segments of foreign DNA, nucleated from a short DNA sequence that was
      complementary by chance, has triggered recombination-dependent replication by
      "join-copy" and "join-cut-copy" pathways that are known to operate in the T-even
      phages and are implicated in other organisms as well. This invasion, accompanied
      by heteroduplex formation between partially similar sequences, and perhaps
      subsequent partial heteroduplex repair, simultaneously substituted T4 gene 69 for
      foreign sequences and scrambled the sequence of the dCTPase gene 56. We suggest
      that similar mechanisms can mobilize DNA segments for horizontal transfer without
      necessarily requiring transposase or site-specific recombination functions.

PMID- 9560367
TI  - DNA polymerase fidelity: from genetics toward a biochemical understanding.
AB  - This review summarizes mutagenesis studies, emphasizing the use of bacteriophage
      T4 mutator and antimutator strains. Early genetic studies on T4 identified
      mutator and antimutator variants of DNA polymerase that, in turn, stimulated the
      development of model systems for the study of DNA polymerase fidelity in vitro.
      Later enzymatic studies using purified T4 mutator and antimutator polymerases
      were essential in elucidating mechanisms of base selection and exonuclease
      proofreading. In both cases, the base analogue 2-aminopurine (2AP) proved
      tremendously useful-first as a mutagen in vivo and then as a probe of DNA
      polymerase fidelity in vitro. Investigations into mechanisms of DNA polymerase
      fidelity inspired theoretical models that, in turn, called for kinetic and
      thermodynamic analyses. Thus, the field of DNA synthesis fidelity has grown from
      many directions: genetics, enzymology, kinetics, physical biochemistry, and
      thermodynamics, and today the interplay continues. The relative contributions of
      hydrogen bonding and base stacking to the accuracy of DNA synthesis are beginning
      to be deciphered. For the future, the main challenges lie in understanding the
      origins of mutational hot and cold spots.

PMID- 9560368
TI  - The mutation rate and cancer.
AB  - The stability of the human genome requires that mutations in the germ line be
      exceptionally rare events. While most mutations are neutral or have deleterious
      effects, a limited number of mutations are required for adaptation to
      environmental changes. Drake has provided evidence that DNA-based microbes have
      evolved a mechanism to yield a common spontaneous mutation rate of approximately
      0.003 mutations per genome per replication (Drake 1991). In contrast, mutation
      rates of RNA viruses are much larger (Holland et al. 1982) and can approach the
      maximum tolerable deleterious mutation rate of one per genome (Eigen and Schuster
      1977; Eigen 1993). Drake calculates that lytic RNA viruses display spontaneous
      mutation rates of approximately one per genome while most have mutation rates
      that are approximately 0.1 per genome (Drake 1993). This constancy of germline
      mutation rates among microbial species need not necessarily mean constancy of the
      somatic mutation rates. Furthermore, there need not be a constant rate for
      somatic mutations during development. In this review, we consider mutations in
      cancer, a pathology in which there appears to be an increase in the rate of
      somatic mutations throughout the genome. Moreover, within the eukaryotic genome,
      as in microbes, there are "hot-spots" that exhibit unusually high mutation
      frequencies. It seems conceivable to us that many tumors contain thousands of
      changes in DNA sequence. The major question is: how do these mutations arise, and
      how many are rate-limiting for tumor progression?

PMID- 9560369
TI  - DNA sequence analysis of spontaneous mutagenesis in Saccharomyces cerevisiae.
AB  - To help elucidate the mechanisms involved in spontaneous mutagenesis, DNA
      sequencing has been applied to characterize the types of mutation whose rates are
      increased or decreased in mutator or antimutator strains, respectively. Increased
      spontaneous mutation rates point to malfunctions in genes that normally act to
      reduce spontaneous mutation, whereas decreased rates are associated with defects
      in genes whose products are necessary for spontaneous mutagenesis. In this
      article, we survey and discuss the mutational specificities conferred by mutator
      and antimutator genes in the budding yeast Saccharomyces cerevisiae. The
      implications of selected aspects of the data are considered with respect to the
      mechanisms of spontaneous mutagenesis.

PMID- 9560370
TI  - Factors affecting inverted repeat stimulation of recombination and deletion in
      Saccharomyces cerevisiae.
AB  - Inverted DNA repeats are an at-risk motif for genetic instability that can induce
      both deletions and recombination in yeast. We investigated the role of the length
      of inverted repeats and size of the DNA separating the repeats for deletion and
      recombination. Stimulation of both deletion and recombination was directly
      related to the size of inverted repeats and inversely related to the size of
      intervening spacers. A perfect palindrome, formed by two 1.0-kb URA3-inverted
      repeats, increased intra- and interchromosomal recombination in the adjacent
      region 2,400-fold and 17,000-fold, respectively. The presence of a strong origin
      of replication in the spacer reduced both rates of deletion and recombination.
      These results support a model in which the stimulation of deletion and
      recombination by inverted repeats is initiated by a secondary structure formed
      between single-stranded DNA of inverted repeats during replication.

PMID- 9560372
TI  - A new look at old mutants of T4 DNA polymerase.

PMID- 9560371
TI  - The chromosome bias of misincorporations during double-strand break repair is not
      altered in mismatch repair-defective strains of Saccharomyces cerevisiae.
AB  - Recombinational repair of a site-specific, double-strand DNA break (DSB) results
      in increased reversion frequency for nearby mutations. Although some models for
      DSB repair predict that newly synthesized DNA will be inherited equally by both
      the originally broken chromosome and the chromosome that served as a template,
      the DNA synthesis errors are almost exclusively found on the chromosome that had
      the original DSB (introduced by the HO endonuclease). To determine whether
      mismatch repair acts on the template chromosome in a directed fashion to restore
      mismatches to the initial sequence, these experiments were repeated in mismatch
      repair-defective (pms1, mlh1, and msh2) backgrounds. The results suggest that
      mismatch repair is not responsible for the observed bias.

PMID- 9560373
TI  - The roles of the bacteriophage T4 r genes in lysis inhibition and fine-structure
      genetics: a new perspective.
AB  - Seldom has the study of a set of genes contributed more to our understanding of
      molecular genetics than has the characterization of the rapid-lysis genes of
      bacteriophage T4. For example, T4 rII mutants were used to define gene structure
      and mutagen effects at the molecular level and to help unravel the genetic code.
      The large-plaque morphology of these mutants reflects a block in expressing lysis
      inhibition (LIN), the ability to delay lysis for several hours in response to
      sensing external related phages attacking the cell, which is a unique and highly
      adaptive attribute of the T4 family of phages. However, surprisingly little is
      known about the mechanism of LIN, or how the various r genes affect its
      expression. Here, we review the extensive old literature about the r genes and
      the lysis process and try to sort out the major players affecting lysis
      inhibition. We confirm that superinfection can induce lysis inhibition even while
      infected cells are lysing, suggesting that the signal response is virtually
      instantaneous and thus probably the result of post-translational regulation. We
      identify the rI gene as ORF tk.-2, based on sequence analysis of canonical rI
      mutants. The rI gene encodes a peptide of 97 amino acids (Mr = 11.1 kD; pI = 4.8)
      that probably is secreted into the periplasmic space. This gene is widely
      conserved among T-even phage. We then present a model for LIN, postulating that
      rI is largely responsible for regulating the gpt holin protein in response to
      superinfection. The evidence suggests that the rIIA and B genes are not directly
      involved in lysis inhibition; rather, when they are absent, an alternate pathway
      for lysis develops which depends on the presence of genes from any of several
      possible prophages and is not sensitive to lysis inhibition.

PMID- 9560374
TI  - Regulation of DNA polymerase exonucleolytic proofreading activity: studies of
      bacteriophage T4 "antimutator" DNA polymerases.

PMID- 9560376
TI  - Differential response of mouse male germ-cell stages to radiation-induced
      specific-locus and dominant mutations.
AB  - In an attempt to provide a systematic assessment of the frequency and nature of
      mutations induced in successive stages of spermato- and spermiogenesis, X
      irradiated male mice were re-mated at weekly intervals, and large samples of
      progeny, observed from birth onward, were scored and genetically tested for
      recessive mutations at seven specific loci and for externally recognizable
      dominant mutations. Productivity findings provided a rough measure of induced
      dominant-lethal frequencies. A qualitative assessment of specific-locus mutations
      (which include deletions and other rearrangements) was made on the basis of
      homozygosity test results, as well as from information derived from more recent
      complementation studies and molecular analyses. Both recessive and dominant
      visibles revealed clear distinctions between spermatogonia and postspermatogonial
      stages. In addition, differences for both of these endpoints, as well as for
      presumed dominant lethals, were found among various postspermatogonial stages. It
      may be concluded that radiation produces its maximum rates of genetic damage in
      germ-cell stages ranging from midpachytene spermatocytes through early
      spermatids, a pattern unlike any of those that have been defined for chemicals;
      further, the frequency peaks for radiation are lower and broader. The difference
      between post-stem-cell stages overall and stem-cell spermatogonia was smaller
      than is generally found with chemicals, not only with respect to the frequency
      but also the nature of mutations.

PMID- 9560375
TI  - Transient and heritable mutators in adaptive evolution in the lab and in nature.
AB  - Major advances in understanding the molecular mechanism of recombination
      dependent stationary-phase mutation in Escherichia coli occurred this past year.
      These advances are reviewed here, and we also present new evidence that the
      mutagenic state responsible is transient. We find that most stationary-phase
      mutants do not possess a heritable stationary-phase mutator phenotype, although a
      small proportion of heritable mutators was found previously. We outline
      similarities between this well-studied system and several recent examples of
      adaptive evolution associated with heritable mutator phenotype in a similarly
      small proportion of survivors of selection in nature and in the lab. We suggest
      the following: (1) Transient mutator states may also be a predominant source of
      adaptive mutations in these latter systems, the heritable mutators being a
      minority (Rosenberg 1997); (2) heritable mutators may sometimes be a product of,
      rather than the cause of, hypermutation that gives rise to adaptive mutations.

PMID- 9560377
TI  - Antimutator mutants in bacteriophage T4 and Escherichia coli.
AB  - Antimutators are mutant strains that have reduced mutation rates compared to the
      corresponding wild-type strain. Their existence, along with mutator mutants that
      have higher mutation rates compared to the wild-type strain, are powerful
      evidence that mutation rates are genetically controlled. Compared to mutator
      mutants, antimutators have a very distinguishing property. Because they prevent
      normally occurring mutations, they, uniquely, are capable of providing insight
      into the mechanisms of spontaneous mutations. In this review, antimutator mutants
      are discussed in bacteriophage T4 and the bacterium Escherichia coli, with regard
      to their properties, possible mechanisms, and implications for the sources of
      spontaneous mutations in these two organisms.

PMID- 9560378
TI  - Damage control: the pleiotropy of DNA repair genes in Drosophila melanogaster.

PMID- 9560380
TI  - Aspects of the ultraviolet photobiology of some T-even bacteriophages.
AB  - Bacteriophage T4 DNA metabolism is largely insulated from that of its host,
      although some host functions assist in the repair of T4 DNA damage. Environmental
      factors sometimes affect survival and mutagenesis after ultraviolet (UV)
      irradiation of T4, and can affect mutagenesis in many organisms. We therefore
      tested the effect of certain environmental factors and host genetic defects upon
      spontaneous and UV-induced mutagenesis and survival in T4 and some related T-even
      phages. Plating at pH 9 enhances UV resistance in T4 by about 14% compared to pH
      7. The host cAMP regulatory system affects host survival after UV irradiation but
      does not affect T4 survival. Thermal rescue, the increasing survival of
      irradiated T4 with increasing plating temperature, occurs also in phage T6, but
      only weakly in phages T2 and RB69; this temperature effect is not altered by
      supplementing infected cells with additional Holliday resolvase (gp49) early in
      infection. Phage RB69 turns out to have almost 50% greater UV resistance than T4,
      but has a genome of about the same size; RB69 is UV-mutable but does not produce
      r mutants, which are easily seen in T2, T4, and T6. Spontaneous mutagenesis in T4
      shows no dependence on medium and little dependence on temperature overall, but
      mutation rates can increase and probably decrease with temperature at specific
      sites. UV mutagenesis is not affected by incubating irradiated particles under
      various conditions before plating, in contrast to phage S13.

PMID- 9560379
TI  - Mutagenesis and more: umuDC and the Escherichia coli SOS response.
AB  - The cellular response to DNA damage that has been most extensively studied is the
      SOS response of Escherichia coli. Analyses of the SOS response have led to new
      insights into the transcriptional and post-translational regulation of processes
      that increase cell survival after DNA damage as well as insights into DNA-damage
      induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and
      umuDC gene products and has as its mechanistic basis the alteration of DNA
      polymerase III such that it becomes capable of replicating DNA containing
      miscoding and noncoding lesions. Ongoing investigations of the mechanisms
      underlying SOS mutagenesis, as well as recent observations suggesting that the
      umuDC operon may have a role in the regulation of the E. coli cell cycle after
      DNA damage has occurred, are discussed.

PMID- 9560382
TI  - Reversion of the tyrosine ochre strain Escherichia coli WU3610 under starvation
      conditions depends on a new gene tas.
AB  - When 3 x 10(8) bacteria of the Escherichia coli tyrA14(oc) leu308(am) strain
      WU3610 are plated on glucose salts agar supplemented with leucine only, colonies
      of slow-growing Tyr+ suppressor mutants begin to appear after about a week and
      increase in numbers roughly linearly with time thereafter (stationary phase or
      starvation-associated mutation). From a library constructed from two of these
      mutants, a clone was obtained that suppressed the tyrosine requirement of WU3610
      when present on a multicopy plasmid. The activity was identified to an open
      reading frame we call tas, the sequence for which has homology with a variety of
      known genes with aldo-keto reductase activity. The activity of tas complements
      the prephenate dehydrogenase dysfunction of tyrA14 (the chorismate mutase
      activity of tyrA possibly being still functional). A strain deleted for tas
      showed no spontaneous mutation under starvation conditions. Whereas neither tas+
      nor tas bacteria showed any increase in viable or total count when plated under
      conditions of tyrosine starvation at 3 x 10(8) cells per plate, at lower density
      (approximately 10(7) per plate) tas+ but not tas bacteria showed considerable
      residual growth. We suggest that the single copy of tas present in WU3610 allows
      cryptic cell or DNA turnover under conditions of tyrosine starvation and that
      this is an essential prerequisite for starvation-associated mutation in this
      system. The target gene for mutation is not tas, although an increase in the
      expression of this gene, for example, resulting from a suppressor mutation
      affecting supercoiling, could be responsible for the slow-growing Tyr+ phenotype.

PMID- 9560381
TI  - Hypermutability in carcinogenesis.
AB  - The presence of numerous chromosomal changes and point mutations in tumors is
      well established. At least some of these changes play a role in the development
      of the tumors. It has been suggested that the number of these genetic changes
      requires that tumorigenesis involves an increase in mutation rate. However, the
      presence of numerous changes can also be accounted for by efficient selection.
      What is required to settle the issue is some measure of nonselected mutations in
      tumors. In order to determine whether the tumor suppressor TP53 (coding for the
      protein p53) is hypermutable at some stage of carcinogenesis, the frequency of
      silent and multiple mutations in this gene has been examined. Silent mutations
      make up approximately 3% of the total recorded but constitute 9.5% of the
      mutations found in tumors with multiple mutations. Multiple closely linked
      mutations are also observed. Such multiple mutations suggest the operation of an
      error-prone replication process in a subclass of cells. The published data
      indicate that TP53 is hypermutable at some stage of tumor development. It is not
      yet clear whether TP53 is unique or whether other genes display a similar pattern
      of silent and multiple mutations.

PMID- 9560383
TI  - Functional overlap in mismatch repair by human MSH3 and MSH6.
AB  - Three human genes, hMSH2, hMSH3, and hMSH6, are homologues of the bacterial MutS
      gene whose products bind DNA mismatches to initiate strand-specific repair of DNA
      replication errors. Several studies suggest that a complex of hMSH2 x hMSH6
      (hMutSalpha) functions primarily in repair of base x base mismatches or single
      extra bases, whereas a hMSH2 x hMSH3 complex (hMutSbeta) functions chiefly in
      repair of heteroduplexes containing two to four extra bases. In the present
      study, we compare results with a tumor cell line (HHUA) that is mutant in both
      hMSH3 and hMSH6 to results with derivative clones containing either wild-type
      hMSH3 or wild-type hMSH6, introduced by microcell-mediated transfer of chromosome
      5 or 2, respectively. HHUA cells exhibit marked instability at 12 different
      microsatellite loci composed of repeat units of 1 to 4 base pairs. Compared to
      normal cells, HHUA cells have mutation rates at the HPRT locus that are elevated
      500-fold for base substitutions and 2400-fold for single-base frameshifts.
      Extracts of HHUA cells are defective in strand-specific repair of substrates
      containing base x base mismatches or 1-4 extra bases. Transfer of either
      chromosome 5 (hMSH3) or 2 (hMSH6) into HHUA cells partially corrects instability
      at the microsatellite loci and also the substitution and frameshift mutator
      phenotypes at the HPRT locus. Extracts of these lines can repair some, but not
      all, heteroduplexes. The combined mutation rate and mismatch repair specificity
      data suggest that both hMSH3 and hMSH6 can independently participate in repair of
      replication errors containing base x base mismatches or 1-4 extra bases. Thus,
      these two gene products share redundant roles in controlling mutation rates in
      human cells.

PMID- 9560384
TI  - Topical reversion at the HIS1 locus of Saccharomyces cerevisiae. A tale of three
      mutants.
AB  - Mutants of the HIS1 locus of the yeast Saccharomyces cerevisiae are suitable
      reporters for spontaneous reversion events because most reversions are topical,
      that is, within the locus itself. Thirteen mutations of his1-1 now have been
      identified with respect to base sequence. Revertants of three mutants and their
      spontaneous reversion rates are presented: (1) a chain termination mutation (his1
      208, nee his1-1) that does not revert by mutations of tRNA loci and reverts only
      by intracodonic suppression; (2) a missense mutation (his1-798, nee his1-7) that
      can revert by intragenic suppression by base substitutions of any sort, including
      a back mutation as well as one three-base deletion; and (3) a -1 frameshift
      mutation (his1-434, nee his1-19) that only reverts topically by +1 back mutation,
      +1 intragenic suppression, or a -2 deletion. Often the +1 insertion is
      accompanied by base substitution events at one or both ends of a run of A's.
      Missense suppressors of his1-798 are either feeders or nonfeeders, and at four
      different locations within the locus, a single base substitution encoding an
      amino acid alteration will suffice to turn the nonfeeder phenotype into a feeder
      phenotype. Late-appearing revertants of his1-798 were found to be slowly growing
      leaky mutants rather than a manifestation of adaptive mutagenesis. Spontaneous
      revertants of his1-208 and his1-434 produced no late-arising colonies.

PMID- 9560385
TI  - The spectrum of acridine resistant mutants of bacteriophage T4 reveals cryptic
      effects of the tsL141 DNA polymerase allele on spontaneous mutagenesis.
AB  - Mutations in the ac gene of bacteriophage T4 confer resistance to acridine
      inhibition of phage development. Previous studies had localized the ac gene
      region; we show that inactivation of T4 Open Reading Frame 52.2 confers the Acr
      phenotype. Thus, 52.2 is ac. The resistance mechanism is unknown. The ac gene
      provides a convenient forward mutagenesis assay. Its compact size (156 bp)
      simplifies mutant sequencing and diverse mutant types are found: base
      substitutions leading to missense or nonsense codons, in-frame deletions or
      duplications within the coding sequence, deletion or duplication frameshifts,
      insertions, complex mutations, and large deletions extending into neighboring
      sequences. Comparisons of spontaneous mutagenesis between phages bearing the wild
      type or tsL141 alleles of DNA polymerase demonstrate that the impact of the
      mutant polymerase is cryptic when total spontaneous mutant frequencies are
      compared, but the DNA sequences of the ac mutants reveal a substantial alteration
      of fidelity by the mutant polymerase. The patterns of base substitution
      mutagenesis suggest that some site-specific mutation rate effects may reflect
      hotspots for mutagenesis arising by different mechanisms. A new class of
      spontaneous duplication mutations, having sequences inconsistent with misaligned
      pairing models, but consistent with nick-processing errors, has been identified
      at a hotspot in ac.

PMID- 9560386
TI  - Rates of spontaneous mutation.
AB  - Rates of spontaneous mutation per genome as measured in the laboratory are
      remarkably similar within broad groups of organisms but differ strikingly among
      groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are
      roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome
      per replication for retroviruses and a retrotransposon. Mutation rates in
      microbes with DNA-based chromosomes are close to 1/300 per genome per
      replication; in this group, therefore, rates per base pair vary inversely and
      hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs.
      Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual
      generation but are currently indistinguishable from 1/300 per cell division per
      effective genome (which excludes the fraction of the genome in which most
      mutations are neutral). It is now possible to specify some of the evolutionary
      forces that shape these diverse mutation rates.

PMID- 9560387
TI  - Regulation of phosphate assimilation in Rhizobium (Sinorhizobium) meliloti.
AB  - We report the isolation of phoB and phoU mutants of the bacterium Rhizobium
      (Sinorhizobium) meliloti. These mutants form N2-fixing nodules on the roots of
      alfalfa plants. R. meliloti mutants defective in the phoCDET (ndvF) encoded
      phosphate transport system grow slowly in media containing 2 mM Pi, and form
      nodules which fail to fix nitrogen (Fix-). We show that the transfer of phoB or
      phoU insertion mutations into phoC mutant strains restores the ability of these
      mutants to: (i) form normal N2-fixing root-nodules, and (ii) grow like the wild
      type in media containing 2 mM Pi. We also show that expression of the alternate
      orfA pit encoded Pi transport system is negatively regulated by the phoB gene
      product, whereas phoB is required for phoCDET expression. We suggest that in R.
      meliloti cells growing under Pi limiting conditions, PhoB protein activates
      phoCDET transcription and represses orfA pit transcription. Our results suggest
      that there are major differences between the Escherichia coli and R. meliloti
      phosphate regulatory systems.

PMID- 9560388
TI  - Cell cycle arrest in cdc20 mutants of Saccharomyces cerevisiae is independent of
      Ndc10p and kinetochore function but requires a subset of spindle checkpoint
      genes.
AB  - The spindle checkpoint ensures accurate chromosome segregation by inhibiting
      anaphase onset in response to altered microtubule function and impaired
      kinetochore function. In this study, we report that the ability of the anti
      microtubule drug nocodazole to inhibit cell cycle progression in Saccharomyces
      cerevisiae depends on the function of the kinetochore protein encoded by NDC10.
      We examined the role of the spindle checkpoint in the arrest in cdc20 mutants
      that arrest prior to anaphase with an aberrant spindle. The arrest in cdc20
      defective cells is dependent on the BUB2 checkpoint and independent of the BUB1,
      BUB3, and MAD spindle checkpoint genes. We show that the lesion recognized by
      Bub2p is not excess microtubules, and the cdc20 arrest is independent of
      kinetochore function. We show that Cdc20p is not required for cyclin proteolysis
      at two points in the cell cycle, suggesting that CDC20 is distinct from genes
      encoding integral proteins of the anaphase promoting complex.

PMID- 9560389
TI  - Identification and characterization of an essential family of inositol
      polyphosphate 5-phosphatases (INP51, INP52 and INP53 gene products) in the yeast
      Saccharomyces cerevisiae.
AB  - We recently demonstrated that the S. cerevisiae INP51 locus (YIL002c) encodes an
      inositol polyphosphate 5-phosphatase. Here we describe two related yeast loci,
      INP52 (YNL106c) and INP53 (YOR109w). Like Inp51p, the primary structures of
      Inp52p and Inp53p resemble the mammalian synaptic vesicle-associated protein,
      synaptojanin, and contain a carboxy-terminal catalytic domain and an amino
      terminal SAC1-like segment. Inp51p (108 kD), Inp52p (136 kD) and Inp53p (124 kD)
      are membrane-associated. Single null mutants (inp51, inp52, or inp53) are viable.
      Both inp51 inp52 and inp52 inp53 double mutants display compromised cell growth,
      whereas an inp51 inp53 double mutant does not. An inp51 inp52 inp53 triple mutant
      is inviable on standard medium, but can grow weakly on media supplemented with an
      osmotic stabilizer (1 M sorbitol). An inp51 mutation, and to a lesser degree an
      inp52 mutation, confers cold-resistant growth in a strain background that cannot
      grow at temperatures below 15 degrees. Analysis of inositol metabolites in vivo
      showed measurable accumulation of phosphatidylinositol 4,5-bisphosphate in the
      inp51 mutant. Electron microscopy revealed plasma membrane invaginations and cell
      wall thickening in double mutants and the triple mutant grown in sorbitol
      containing medium. A fluorescent dye that detects endocytic and vacuolar
      membranes suggests that the vacuole is highly fragmented in inp51 inp52 double
      mutants. Our observations indicate that Inp51p, Inp52p, and Inp53p have distinct
      functions and that substrates and/or products of inositol polyphosphate 5
      phosphatases may have roles in vesicle trafficking, membrane structure, and/or
      cell wall formation.

PMID- 9560390
TI  - Sum1, a highly conserved WD-repeat protein, suppresses S-M checkpoint mutants and
      inhibits the osmotic stress cell cycle response in fission yeast.
AB  - The S-M checkpoint ensures that entry into mitosis is dependent on completion of
      DNA replication. In the fission yeast Schizosaccharomyces pombe, the SM
      checkpoint mutant cdc2-3w is thought to be defective in receiving the checkpoint
      signal. To isolate genes that function in the checkpoint pathway, we screened an
      S. pombe cDNA library for genes that, when overexpressed, could suppress the
      checkpoint defect of cdc2-3w. Using this approach, we have identified a novel
      gene, sum1+ (suppressor of uncontrolled mitosis). sum1+ encodes a highly
      conserved WD-transducin repeat protein with striking sequence similarity to the
      human transforming growth factor (TGF)-beta-receptor interacting protein TRIP-1
      and to the translation initiation factor 3 subunit eIF3-p39, encoded by the TIF34
      gene in Saccharomyces cerevisiae. S. pombe sum1+ is an essential gene, required
      for normal cell growth and division. In addition to restoring checkpoint control,
      overexpression of sum1+ inhibits the normal cell cycle response to osmotic
      stress. Furthermore, we demonstrate that inactivation of the stress-activated MAP
      kinase pathway, required for cell cycle stress response, restores the S-M
      checkpoint in cdc2-3w cells. These results suggest that Suml interacts with the
      stress-activated MAP kinase pathway and raise the possibility that environmental
      conditions may influence the checkpoint response in fission yeast.

PMID- 9560392
TI  - Cdc1 is required for growth and Mn2+ regulation in Saccharomyces cerevisiae.
AB  - Cdc1 function was initially implicated in bud formation and nuclear division
      because cdc1(Ts) cells arrested with a small bud, duplicated DNA, and undivided
      nucleus. Our studies show that Cdc1 is necessary for cell growth at several
      stages of the cell cycle, as well as in pheromone-treated cells. Thus, Cdc1
      depletion might affect bud formation and nuclear division, as well as other
      cellular processes, by blocking a process involved in general cell growth. Cells
      depleted of intracellular Mn2+ also exhibit a cdc1-like phenotype and recent
      results suggested Cdc1 might be a Mn2+-dependent protein. We show that all of the
      conditional Cdc1(Ts) alleles tested cause cells to become sensitive to Mn2+
      depletion. In addition, Cdc1 overproduction alleviates the chelator sensitivity
      of several Mn2+ homeostasis mutants. These findings are compatible with a model
      in which Cdc1 regulates intracellular, and in particular cytosolic, Mn2+ levels
      which, in turn, are necessary for cell growth.

PMID- 9560391
TI  - Posttranslational inhibition of Ty1 retrotransposition by nucleotide excision
      repair/transcription factor TFIIH subunits Ssl2p and Rad3p.
AB  - rtt4-1 (regulator of Ty transposition) is a cellular mutation that permits a high
      level of spontaneous Ty1 retrotransposition in Saccharomyces cerevisiae. The RTT4
      gene is allelic with SSL2 (RAD25), which encodes a DNA helicase present in basal
      transcription (TFIIH) and nucleotide excision repair (NER) complexes. The ssl2
      rtt (rtt4-1) mutation stimulates Ty1 retrotransposition, but does not alter Ty1
      target site preferences, or increase cDNA or mitotic recombination. In addition
      to ssl2-rtt, the ssl2-dead and SSL2-1 mutations stimulate Ty1 transposition
      without altering the level of Ty1 RNA or proteins. However, the level of Ty1 cDNA
      markedly increases in the ssl2 mutants. Like SSL2, certain mutations in another
      NER/TFIIH DNA helicase encoded by RAD3 stimulate Ty1 transposition. Although
      Ssl2p and Rad3p are required for NER, inhibition of Ty1 transposition is
      independent of Ssl2p and Rad3p NER functions. Our work suggests that NER/TFIIH
      subunits antagonize Ty1 transposition posttranslationally by inhibiting reverse
      transcription or destabilizing Ty1 cDNA.

PMID- 9560393
TI  - Cdc1 and the vacuole coordinately regulate Mn2+ homeostasis in the yeast
      Saccharomyces cerevisiae.
AB  - The yeast CDC1 gene encodes an essential protein that has been implicated in the
      regulation of cytosolic [Mn2+]. To identify factors that impinge upon Cdc1 or the
      Cdc1-dependent process, we isolated second-site suppressors of the conditional
      cdc1-1(Ts) growth defect. Recessive suppressors define 15 COS (CdcOne Suppressor)
      genes. Seven of the fifteen COS genes are required for biogenesis of the vacuole,
      an organelle known to sequester intracellular Mn2+. An eighth gene, COS16,
      encodes a vacuolar membrane protein that seems to be involved in Mn2+
      homeostasis. These results suggest mutations that block vacuolar Mn2+
      sequestration compensate for defects in Cdc1 function. Interestingly, Cdc1 is
      dispensable in a cos16delta deletion strain, and a cdc1delta cos16delta double
      mutant exhibits robust growth on medium supplemented with Mn2+. Thus, the single,
      essential function of Cdc1 is to regulate intracellular, probably cytosolic,
      Mn2+.

PMID- 9560394
TI  - Isolation and characterization of fission yeast sns mutants defective at the
      mitosis-to-interphase transition.
AB  - pim1-d1ts was previously identified in a visual screen for fission yeast mutants
      unable to complete the mitosis-to-interphase transition. pim1+ encodes the
      guanine nucleotide exchange factor (GEF) for the spi1 GTPase. Perturbations of
      this GTPase system by either mutation or overproduction of its regulatory
      proteins cause cells to arrest with postmitotic condensed chromosomes, an
      unreplicated genome, and a wide medial septum. The septation phenotype of pim1
      d1ts was used as the basis for a more extensive screen for this novel class of
      sns (septated, not in S-phase) mutants. Seventeen mutants representing 14
      complementation groups were isolated. Three strains, sns-A3, sns-A5, and sns-A6,
      representing two different alleles, are mutated in the pim1+ gene. Of the 13 non
      pim1ts sns complementation groups, 11 showed genetic interactions with the spi1
      GTPase system. The genes mutated in 10 sns strains were synthetically lethal with
      pim1-d1, and six sns strains were hypersensitive to overexpression of one or more
      of the known components of the spil GTPase system. Epistasis analysis places the
      action of the genes mutated in nine of these strains downstream of pim1+ and the
      action of one gene upstream of pim1+. Three strains, sns-A2, sns-B1, and sns-B9,
      showed genetic interaction with the spil GTPase system in every test performed.
      sns-B1 and sns-B9 are likely to identify downstream targets, whereas sns-A2 is
      likely to identify upstream regulators of the spi1 GTPase system that are
      required for the mitosis-to-interphase transition.

PMID- 9560395
TI  - The fluffy gene of Neurospora crassa encodes a Gal4p-type C6 zinc cluster protein
      required for conidial development.
AB  - Neurospora crassa fluffy (fl) mutants are unable to produce macroconidia. We
      cloned the fl gene to determine its role in regulating conidiation. A cosmid
      clone containing fl was identified by complementation. The sequence of fl
      revealed that it encodes a Gal4p-type C6 zinc cluster protein with greatest
      similarity to the N. crassa NIT4 protein that regulates genes required for
      nitrate utilization. Analysis of several fl mutant alleles demonstrated that null
      mutants are blocked in the budding phase of development required to produce
      conidiophores. fl mRNA is transiently induced just prior to the developmental
      commitment to budding growth. This timing of fl expression is consistent with a
      role for FL protein in activation of the previously characterized conidiation
      specific (con) genes, con-6 and con-10. These data suggest that FL acts as a
      developmentally regulated transcription factor required for conidiophore
      morphogenesis.

PMID- 9560396
TI  - High-efficiency transformation of Chlamydomonas reinhardtii by electroporation.
AB  - We have established a high-efficiency method for transforming the unicellular,
      green alga Chlamydomonas reinhardtii by electroporation. Electroporation of
      strains CC3395 and CC425, cell wall-less mutants devoid of argininosuccinate
      lyase (encoded by ARG7), in the presence of the plasmid pJD67 (which contains
      ARG7) was used to optimize conditions for the introduction of exogenous DNA. The
      conditions that were varied included osmolarity, temperature, concentration of
      exogenous DNA, voltage and capacitance. Following optimization, the maximum
      transformation frequency obtained was 2 x 10(5) transformants per microg of DNA;
      this frequency is two orders of magnitude higher than obtained with the current
      standard method using glass beads to introduce exogenous DNA. The electroporation
      procedure described in this article is of general utility, and makes it feasible
      to isolate genes by direct complementation of Chlamydomonas reinhardtii mutants.

PMID- 9560397
TI  - High frequency recombination during the sexual cycle of Dictyostelium discoideum.
AB  - Analysis of Dictyostelium development and cell biology has suffered from the lack
      of an ordinary genetic system whereby genes can be arranged in new combinations.
      Genetic exchange between two long ignored strains, A2Cycr and WS205 is here
      reexamined. Alleles which differ in size or restriction sites between these two
      strains were found for seven genes. Six of these are in two clusters on
      chromosome 2. Frequencies of recombinant progeny indicate that the genetic map of
      the two mating strains is colinear with the physical map recently worked out for
      the standard nonsexual strain, NC4. The rate of recombination is high, about 0.1%
      per kilobase in three different regions of chromosome 2. This value is comparable
      to rates found in yeast, and will permit fine dissection of the genome.

PMID- 9560398
TI  - Effects of A and B Wolbachia and host genotype on interspecies cytoplasmic
      incompatibility in Nasonia.
AB  - Wolbachia endosymbionts cause postmating reproductive isolation between the
      sibling species Nasonia vitripennis and N. giraulti. Most Nasonia are doubly
      infected with a representative from each of the two major Wolbachia groups (A and
      B). This study investigates the role of single (A or B) and double (A and B)
      Wolbachia infections in interspecies cytoplasmic incompatibility (CI) and host
      genomic influences on the incompatibility phenotype. Results show that the single
      A Wolbachia harbored in N. vitripennis (wAv) is bidirectionally incompatible with
      the single A Wolbachia harbored in N. giraulti (wAg). Results also indirectly
      show that the N. vitripennis wBv is bidirectionally incompatible with the N.
      giraulti wBg. The findings support current phylogenetic evidence that suggests
      these single infections have independent origins and were acquired via horizontal
      transfer. The wAv Wolbachia expresses partial CI in the N. vitripennis nuclear
      background. However, following genomic replacement by introgression, wAv
      expresses complete CI in the N. giraulti background and remains bidirectionally
      incompatible with wAg. Results show that double infections can reinforce
      interspecies reproductive isolation through the addition of incompatibility types
      and indicate that the host genome can influence incompatibility levels. This
      study has implications for host-symbiont coevolution and the role of Wolbachia in
      speciation.

PMID- 9560399
TI  - Second-site noncomplementation identifies genomic regions required for Drosophila
      nonmuscle myosin function during morphogenesis.
AB  - Drosophila is an ideal metazoan model system for analyzing the role of nonmuscle
      myosin-II (henceforth, myosin) during development. In Drosophila, myosin function
      is required for cytokinesis and morphogenesis driven by cell migration and/or
      cell shape changes during oogenesis, embryogenesis, larval development and pupal
      metamorphosis. The mechanisms that regulate myosin function and the
      supramolecular structures into which myosin incorporates have not been
      systematically characterized. The genetic screens described here identify genomic
      regions that uncover loci that facilitate myosin function. The nonmuscle myosin
      heavy chain is encoded by a single locus, zipper. Contiguous chromosomal
      deficiencies that represent approximately 70% of the euchromatic genome were
      screened for genetic interactions with two recessive lethal alleles of zipper in
      a second-site noncomplementation assay for the malformed phenotype. Malformation
      in the adult leg reflects aberrations in cell shape changes driven by myosin
      based contraction during leg morphogenesis. Of the 158 deficiencies tested, 47
      behaved as second-site noncomplementors of zipper. Two of the deficiencies are
      strong interactors, 17 are intermediate and 28 are weak. Finer genetic mapping
      reveals that mutations in cytoplasmic tropomyosin and viking (collagen IV) behave
      as second-site noncomplementors of zipper during leg morphogenesis and that
      zipper function requires a previously uncharacterized locus, E3.10/J3.8, for leg
      morphogenesis and viability.

PMID- 9560400
TI  - A proline-rich region in the Zeste protein essential for transvection and white
      repression by Zeste.
AB  - The DNA-binding protein encoded by the zeste gene of Drosophila activates
      transcription and mediates interchromosomal interactions such as transvection.
      The mutant protein encoded by the zeste1 (z1) allele retains the ability to
      support transvection, but represses white. Similar to transvection, repression
      requires Zeste-Zeste protein interactions and a second copy of white, either on
      the homologous chromosome or adjacent on the same chromosome. We characterized
      two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c)
      that represses white. The z1 lesion alters a lysine residue located between the N
      terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in
      Zeste self-interactions. The z78c mutation alters a histidine near the site of
      the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different
      prolines in a proline-rich region located between the z1 lesion and the self
      interaction domain. The pseudorevertants retain the ability to self-interact, but
      fail to repress white or support transvection at Ultrabithorax. To account for
      these observations and evidence indicating that Zeste affects gene expression
      through Polycomb group (Pc-G) protein complexes that epigenetically maintain
      chromatin states, we suggest that the regions affected by the z1, z78c, and
      pseudorevertant lesions mediate interactions between Zeste and the maintenance
      complexes.

PMID- 9560401
TI  - Evidence for a multistep control in transposition of I factor in Drosophila
      melanogaster.
AB  - Drosophila melanogaster strains belong to one of two interactive categories,
      inducer (I) or reactive (R), with respect to the I-R system of hybrid dysgenesis.
      The dysgenic interaction results from the presence of several transposition
      competent copies of a LINE-like element, the I factor, only in the genome of I
      strains. When a cross is performed between I males and R females, I factor
      transposes at high frequency in the germ line of F1 daughters, known as SF
      females. This transposition burst results in the sterility of SF females. I
      factor transposes by reverse transcription of a full-length transcript. Specific
      RT-PCR experiments were done to compare the amount of I factor transcript in
      samples corresponding to various transposition frequencies. The sensitivity of
      the method allowed the ready detection of the I factor RNA in every tissue and
      genetic background examined. Comparison of amplification signals suggests that I
      factor activity in ovaries is regulated at different levels. First, the amount of
      I factor RNA subjected to negative and positive regulation. Whereas the negative
      control, which limits transposition in nonpermissive contexts, may be exerted by
      an I factor encoded repressor function, the positive control is linked to
      reactivity level, a cellular state maternally inherited from R mothers.
      Additionally, negative regulation is also exerted downstream of I factor RNA.
      This differs notably from previous conclusions in which transcription was
      envisaged as the main level of regulation of the I factor transposition.

PMID- 9560402
TI  - Epistatic interactions between smell-impaired loci in Drosophila melanogaster.
AB  - Odor-guided behavior is a polygenic trait determined by the concerted expression
      of multiple loci. Previously, P-element mutagenesis was used to identify single
      P[lArB] insertions, in a common isogenic background, with homozygous effects on
      olfactory behavior. Here, we have crossed 12 lines with these smell impaired
      (smi) mutations in a half-diallel design (excluding homozygous parental genotypes
      and reciprocal crosses) to produce all possible 66 doubly heterozygous hybrids
      with P[lArB] insertions at two distinct locations. The olfactory behavior of the
      transheterozygous progeny was measured using an assay that quantified the
      avoidance response to the repellent odorant benzaldehyde. There was significant
      variation in general combining abilities of avoidance scores among the smi
      mutants, indicating variation in heterozygous effects. Further, there was
      significant variation among specific combining abilities of each cross,
      indicating dependencies of heterozygous effects on the smi locus genotypes, i.e.,
      epistasis. Significant epistatic interactions were identified for nine
      transheterozygote genotypes, involving 10 of the 12 smi loci. Eight of these loci
      form an interacting ensemble of genes that modulate expression of the behavioral
      phenotype. These observations illustrate the power of quantitative genetic
      analyses to detect subtle phenotypic effects and point to an extensive network of
      epistatic interactions among genes in the olfactory subgenome.

PMID- 9560403
TI  - Early effect of inbreeding as revealed by microsatellite analyses on Ostrea
      edulis larvae.
AB  - This paper reports new experimental evidence on the effect of inbreeding on
      growth and survival in the early developmental phase of a marine bivalve, the
      flat oyster Ostrea edulis. Two crosses between full sibs were analyzed using four
      microsatellite markers. Samples of 96 individuals were taken just after spawning
      (day 1), at the end of the larval stage before metamorphosis (day 10) and at the
      postlarval stage (day 70). Significant departure from Mendelian expectation was
      observed at two loci in the first cross and two loci in the second. Departure
      from 1:1 segregation occurred in one parent of the first cross at three loci and
      genotypic selection, which resulted in highly significant heterozygote excesses,
      was recorded at three out of four loci in cross C1 and at two out of three loci
      in cross C2. Across the four markers, there were similar significant excesses of
      multilocus heterozygosity, and significant multilocus heterozygosity-growth
      correlations were recorded for both crosses at all stages. These results suggest
      that microsatellite markers, often assumed to be neutral, cosegregated with
      fitness-associated genes, the number of which is estimated to be between 15 and
      38 in the whole genome, and that there is a potentially high genetic load in
      Ostrea edulis genome. This load provides a genetic basis for heterosis in marine
      bivalves.

PMID- 9560404
TI  - Heteroplasmy, length and sequence variation in the mtDNA control regions of three
      percid fish species (Perca fluviatilis, Acerina cernua, Stizostedion lucioperca).
AB  - The nucleotide sequence of the control region and flanking tRNA genes of perch
      (Perca fluviatilis) mtDNA was determined. The organization of this region is
      similar to that of other vertebrates. A tandem array of 10-bp repeats, associated
      with length variation and heteroplasmy was observed in the 5' end. While the
      location of the array corresponds to that reported in other species, the length
      of the repeated unit is shorter than previously observed for tandem repeats in
      this region. The repeated sequence was highly similar to the Mt5 element which
      has been shown to specifically bind a putative D-loop DNA termination protein. Of
      149 perch analyzed, 74% showed length variation heteroplasmy. Single-cell PCR on
      oocytes suggested that the high level of heteroplasmy is passively maintained by
      maternal transmission. The array was also observed in the two other percid
      species, ruffe (Acerina cernua) and zander (Stizostedion lucioperca). The array
      and the associated length variation heteroplasmy are therefore likely to be
      general features of percid mtDNAs. Among the perch repeats, the mutation pattern
      is consistent with unidirectional slippage, and statistical analyses supported
      the notion that the various haplotypes are associated with different levels of
      heteroplasmy. The variation in array length among and within species is ascribed
      to differences in predicted stability of secondary structures made between repeat
      units.

PMID- 9560405
TI  - Signatures of population expansion in microsatellite repeat data.
AB  - To examine the signature of population expansion on genetic variability at
      microsatellite loci, we consider a population that evolves according to the time
      continuous Moran model, with growing population size and mutations that follow a
      general asymmetric stepwise mutation model. We present calculations of expected
      allele-size variance and homozygosity at a locus in such a model for several
      variants of growth, including stepwise, exponential, and logistic growth. These
      calculations in particular prove that population bottleneck followed by growth in
      size causes an imbalance between allele size variance and heterozygosity,
      characterized by the variance being transiently higher than expected under
      equilibrium conditions. This effect is, in a sense, analogous to that
      demonstrated before for the infinite allele model, where the number of alleles
      transiently increases after a stepwise growth of population. We analyze a set of
      data on tetranucleotide repeats that reveals the imbalance expected under the
      assumption of bottleneck followed by population growth in two out of three major
      racial groups. The imbalance is strongest in Asians, intermediate in Europeans,
      and absent in Africans. This finding is consistent with previous findings by
      others concerning the population expansion of modern humans, with the bottleneck
      event being most ancient in Africans, most recent in Asians, and intermediate in
      Europeans. Nevertheless, the imbalance index alone cannot reliably estimate the
      time of initiation of population expansion.

PMID- 9560406
TI  - Genetic basis of response to 50 generations of selection on body weight in inbred
      mice.
AB  - A long-established inbred strain of mice was divergently selected for body weight
      for 50 generations. Selection of new mutations affecting the trait eventually led
      to a divergence of approximately three phenotypic standard deviations between the
      high and low lines. Heritability for body weight increased at a rate between
      0.23% and 0.57% per generation from new mutations, depending on the genetic model
      assumed. About two-thirds of the selection response was in the upward direction.
      The response was episodic, suggesting a substantial contribution from the
      selection of mutations with large effects on the trait. A maximum likelihood
      procedure was used to estimate the number of factors contributing to the response
      using data from line crosses, with models of n equivalent gene effects (i.e., to
      estimate the Wright-Castle index), or n genes with variable effects. The results
      of the analysis of data from a cross between the selected high line and an
      unselected control line indicated that two major factors were involved, with the
      suggestion of an additional minor factor.

PMID- 9560407
TI  - Chromosome 14 contains determinants that regulate susceptibility to Theiler's
      virus-induced demyelination in the mouse.
AB  - Theiler's murine encephalomyelitis virus causes a chronic demyelinating disease
      in susceptible strains of mice that is similar to human multiple sclerosis.
      Several nonmajor histocompatibility complex-linked genes have been implicated as
      determinants of susceptibility or resistance to either demyelination or virus
      persistence. In this study, we used linkage analysis of major histocompatibility
      complex identical H-2d (DBA/2J x B10.D2) F2 intercross mice to identify loci
      associated with susceptibility to virus-induced demyelinating disease. In a 20-cM
      region on chromosome 14, we identified four markers, D14Mit54, D14Mit60,
      D14Mit61, and D14Mit90 that are significantly associated with demyelination.
      Because two peaks were identified, one near D14Mit54 and one near D14Mit90, it is
      possible that two loci in this region are involved in controlling demyelination.

PMID- 9560408
TI  - Molecular genetic dissection of mouse unconventional myosin-VA: head region
      mutations.
AB  - The mouse dilute (d) locus encodes unconventional myosin-VA (MyoVA). Mice
      carrying null alleles of dilute have a lightened coat color and die from a
      neurological disorder resembling ataxia and opisthotonus within three weeks of
      birth. Immunological and ultrastructural studies suggest that MyoVA is involved
      in the transport of melanosomes in melanocytes and smooth endoplasmic reticulum
      in cerebellar Purkinje cells. In studies described here, we have used an RT-PCR
      based sequencing approach to identify the mutations responsible for 17 viable
      dilute alleles that vary in their effects on coat color and the nervous system.
      Seven of these mutations mapped to the MyoVA motor domain and are reported here.
      Crystallographic modeling and mutant expression studies were used to predict how
      these mutations might affect motor domain function and to attempt to correlate
      these effects with the mutant phenotype.

PMID- 9560409
TI  - Molecular genetic dissection of mouse unconventional myosin-VA: tail region
      mutations.
AB  - We used an RT-PCR-based sequencing approach to identify the mutations responsible
      for 17 viable dilute alleles, a mouse-coat-color locus encoding unconventional
      myosin-VA. Ten of the mutations mapped to the MyoVA tail and are reported here.
      These mutations represent the first extensive collection of tail mutations
      reported for any unconventional mammalian myosin. They identify sequences
      important for tail function and identify domains potentially involved in cargo
      binding and/or proper folding of the MyoVA tail. Our results also provide support
      for the notion that different myosin tail isoforms produced by alternative
      splicing encode important cell-type-specific functions.

PMID- 9560410
TI  - Paramutation of the r1 locus of maize is associated with increased cytosine
      methylation.
AB  - In paramutation two alleles of a gene interact so that one of the alleles is
      epigenetically silenced. The silenced state is then genetically transmissible for
      many generations. The large (220 kbp) multigenic complex R-r is paramutable: its
      level of expression is changed during paramutation. R-r was found to exhibit
      increases in its level of cytosine methylation (C-methylation) following
      paramutation. These C-methylation changes are localized to the 5' portions of the
      two genes in the complex that are most sensitive to paramutation. These
      methylation changes flank a small region called sigma that is thought to have
      been derived from a transposon named doppia. A mutant derivative of R-r that has
      a deletion of the sigma region fails to become methylated under conditions in
      which R-r is heavily methylated. This suggests that the presence of sigma
      sequences at the locus is required for the methylation changes that are observed
      following paramutation.

PMID- 9560411
TI  - Physical mapping of the liguleless linkage group in Sorghum bicolor using rice
      RFLP-selected sorghum BACs.
AB  - Physical mapping of BACs by fluorescent in situ hybridization (FISH) was used to
      analyze the liguleless (lg-1) linkage group in sorghum and compare it to the
      conserved region in rice and maize. Six liguleless-associated rice restriction
      fragment length polymorphism (RFLP) markers were used to select 16 homeologous
      sorghum BACs, which were in turn used to physically map the liguleless linkage
      group in sorghum. Results show a basic conservation of the liguleless region in
      sorghum relative to the linkage map of rice. One marker which is distal in rice
      is more medial in sorghum, and another marker which is found within the linkage
      group in rice is on a different chromosome in sorghum. BACs associated with
      linkage group I hybridize to chromosome It, which was identified by using FISH in
      a sorghum cytogenetic stock trisomic for chromosome I (denoted It), and a BAC
      associated with linkage group E hybridized to an unidentified chromosome.
      Selected BACs, representing RFLP loci, were end-cloned for RFLP mapping, and the
      relative linkage order of these clones was in full agreement with the physical
      data. Similarities in locus order and the association of RFLP-selected BAC
      markers with two different chromosomes were found to exist between the linkage
      map of the liguleless region in maize and the physical map of the liguleless
      region in sorghum.

PMID- 9560412
TI  - High apparent rate of simultaneous compensatory base-pair substitutions in
      ribosomal RNA.
AB  - We present a model for the evolution of paired bases in RNA sequences. The new
      model allows for the instantaneous rate of substitution of both members of a base
      pair in a compensatory substitution (e.g., A-U-->G-C) and expands our previous
      work by allowing for unpaired bases or noncanonical pairs. We implemented the
      model with distance and maximum likelihood methods to estimate the rates of
      simultaneous substitution of both bases, alphad, vs. rates of substitution of
      individual bases, alphas in rRNA. In the rapidly evolving D2 expansion segments
      of Drosophila large subunit rRNA, we estimate a low ratio of alphad/alphas,
      indicating that most compensatory substitutions involve a G-U intermediate. In
      contrast, we find a surprisingly high ratio of alphad/alphas in the core small
      subunit rRNA, indicating that the evolution of the slowly evolving rRNA sequences
      is modeled much more accurately if simultaneous substitution of both members of a
      base pair is allowed to occur approximately as often as substitution of
      individual bases. Using simulations, we have ruled out several potential sources
      of error in the estimation of alphad/alphas. We conclude that in the core rRNA
      sequences compensatory substitutions can be fixed so rapidly as to appear to be
      instantaneous.

PMID- 9560413
TI  - Estimating within-locus nonadditive coefficient and discriminating dominance
      versus overdominance as the genetic cause of heterosis.
AB  - Testing (over)dominance as the genetic cause of heterosis and estimating the
      (over)dominance coefficient (h) are related. Using simulations, we investigate
      the statistical properties of Mukai's approach, which is intended to estimate the
      average (h) of hi across loci by regression of outcrossed progeny on the sum of
      the two corresponding homozygous parents. A new approach for estimating h is also
      developed, utilizing data on families formed by multiple selfed genotypes from
      each outcrossed parent, thus not requiring constructing homozygotes. Assuming
      constant mutation effects, h can be estimated accurately by both approaches under
      dominance. When rare alleles have low frequencies at any polymorphic locus,
      Mukai's approach can estimate h accurately under over(under)dominance. Therefore,
      the (over)dominance hypothesis for heterosis can be tested by estimating h, under
      either dominance or overdominance at all genomic loci. However, this is invalid
      with more plausible mixed dominance and overdominance at different loci.
      Estimating the variance of hi across loci is also investigated. In self
      compatible outcrossing populations with mutations of variable effects and
      lethals, our new approach is better than Mukai's, not only because of not
      requiring homozygotes but also because of the better statistical performance
      reflected by the smaller mean square errors of the estimates.

PMID- 9560414
TI  - Approximate analysis of QTL-environment interaction with no limits on the number
      of environments.
AB  - An approach is presented here for quantitative trait loci (QTL) mapping analysis
      that allows for QTL x environment (E) interaction across multiple environments,
      without necessarily increasing the number of parameters. The main distinction of
      the proposed model is in the chosen way of approximation of the dependence of
      putative QTL effects on environmental states. We hypothesize that environmental
      dependence of a putative QTL effect can be represented as a function of
      environmental mean value of the trait. Such a description can be applied to take
      into account the effects of any cosegregating QTLs from other genomic regions
      that also may vary across environments. The conducted Monte-Carlo simulations and
      the example of barley multiple environments experiment demonstrate a high
      potential of the proposed approach for analyzing QTL x E interaction, although
      the results are only approximated by definition. However, this drawback is
      compensated by the possibility to utilize information from a potentially
      unlimited number of environments with a remarkable reduction in the number of
      parameters, as compared to previously proposed mapping models with QTL x E
      interactions.

PMID- 9560415
TI  - Genetic diversity at a single locus under viability selection and facultative
      apomixis: equilibrium structure and deviations from Hardy-Weinberg frequencies.
AB  - We extensively analyze the maintenance of genetic variation and deviations from
      Hardy-Weinberg frequencies at a diallelic locus under mixed mating with apomixis
      and constant viability selection. Analytical proofs show that: (1) at most one
      polymorphic equilibrium exists, (2) polymorphism requires overdominant or
      underdominant selection, and (3) a simple, modified overdominance condition is
      sufficient to maintain genetic variation. In numerical analyses, only
      overdominant polymorphic equilibria are stable, and these are stable whenever
      they exist, which happens for approximately 78% of random fitness and mating
      parameters. The potential for maintaining both alleles increases with increasing
      apomixis or outcrossing and decreasing selfing. Simulations also indicate that
      equilibrium levels of heterozygosity will often be statistically
      indistinguishable from Hardy-Weinberg frequencies and that adults, not seeds,
      should usually be censused to maximize detecting deviations. Furthermore,
      although both censuses more often have an excess rather than a deficit of
      heterozygotes, analytical sign analyses of the fixation indices prove that,
      overall, adults are more likely to have an excess and seeds a deficit at
      equilibrium.

PMID- 9560416
TI  - The oxygen-responsive NIFL-NIFA complex: a novel two-component regulatory system
      controlling nitrogenase synthesis in gamma-proteobacteria.
AB  - The high energetic requirements for nitrogen fixation and the extreme oxygen
      sensitivity of the nitrogenase enzyme impose physiological constraints on
      diazotrophy that necessitate stringent control of nitrogen fixation (nif) gene
      expression at the transcriptional level. In the gamma-subdivision of the
      Proteobacteria, this control is maintained by a regulatory complex comprising an
      enhancer-binding protein (NIFA), which activates transcription at sigmaN
      dependent nif (nitrogen fixation) promoters, and a sensor protein (NIFL), which
      inhibits NIFA activity in response to fixed nitrogen and external concentrations
      of molecular oxygen. Inhibition of NIFA activity by NIFL apparently requires
      stoichiometric amounts of the two proteins, implying direct protein-protein
      interaction rather than catalytic modulation of NIFA activity. NIFL contains FAD
      as a prosthetic group and is a novel type of flavoprotein in which the oxidation
      state of the bound flavin acts as a molecular switch to control transcriptional
      activation by NIFA. The FAD-binding domain of NIFL contains a motif common to a
      large family of redox sensory proteins. In addition to its ability to act as a
      redox sensor, the activity of NIFL is also responsive to adenosine nucleotides,
      particularly ADP, suggesting that formation of the inhibitory complex might be
      regulated by the ATP/ ADP ratio. Proposed mechanisms for the inhibition of NIFA
      activity by NIFL are beginning to emerge.

PMID- 9560417
TI  - Characterization of a new Agrobacterium tumefaciens strain from alfalfa.
AB  - Agrobacterium tumefaciens strain 1D1609 is reported here as the first field
      isolate from alfalfa (Medicago sativa L.). Unlike well-characterized A.
      tumefaciens strains such as C58 and Ach5, strain 1D1609 is highly virulent on
      alfalfa and has a distinctive host range. Interestingly, strain 1D1609 is
      naturally resistant to kanamycin and spectinomycin. The Ti plasmid in strain
      1D1609 is an octopine-type; thus, tumors formed by strain 1D1609 synthesize
      octopine, which is utilized by the bacterium as a sole carbon source. Reciprocal
      exchange of Ti plasmids between strains 1D1609 and C58 showed that both
      chromosomal and Ti plasmid genes in strain 1D1609 contribute specifically to
      tumor formation on alfalfa. In addition, the nondormant CUF101 alfalfa cultivar
      from which strain 1D1609 was isolated was significantly more susceptible to all
      Agrobacterium strains tested than was the dormant Agate cultivar.

PMID- 9560418
TI  - Rapid identification of wine yeast species based on RFLP analysis of the
      ribosomal internal transcribed spacer (ITS) region.
AB  - In this study, we identified a total of 33 wine yeast species and strains using
      the restriction patterns generated from the region spanning the internal
      transcribed spacers (ITS 1 and 2) and the 5.8S rRNA gene. Polymerase chain
      reaction (PCR) products of this rDNA region showed a high length variation for
      the different species. The size of the PCR products and the restriction analyses
      with three restriction endonucleases (HinfI, CfoI, and HaeIII) yielded a specific
      restriction pattern for each species with the exception of the corresponding
      anamorph and teleomorph states, which presented identical patterns. This method
      was applied to analyze the diversity of wine yeast species during spontaneous
      wine fermentation.

PMID- 9560419
TI  - The Helicobacter felis ftsH gene encoding an ATP-dependent metalloprotease can
      replace the Escherichia coli homologue for growth and phage lambda
      lysogenization.
AB  - Cloning and sequencing of an approximately 6.0-kb chromosomal DNA fragment from
      Helicobacter felis revealed five complete open reading frames. The deduced amino
      acid sequence of one ORF exhibited sequence similarity to the FtsH protein, an
      ATP-dependent metalloprotease, from various bacterial species. The encoded
      protein consists of 638 amino acid residues with a molecular mass of 70.2 kDa.
      The hydropathy profile of the FtsH protein predicted two N-terminal transmembrane
      regions that were confirmed experimentally. Insertion of ftsH into a new
      versatile expression vector resulted in overexpression of FtsH protein in
      Escherichia coli. In addition, the E. coli ftsH gene could be replaced by the H.
      felis homologue to allow reduced growth and tenfold increased lysogenization by
      temperate phage lambda.

PMID- 9560420
TI  - Phylogenetic analysis of Methanobrevibacter isolated from feces of humans and
      other animals.
AB  - Comparative 16S rRNA gene sequence and genomic DNA reassociation analyses were
      used to assess the phylogenetic relationships of Methanobrevibacter fecal
      isolates. The 16S rRNA gene sequences of Methanobrevibacter smithii strain PS and
      the human fecal isolates B181 and ALI were essentially identical, and their
      genomic DNA reassociated at values greater than 94%. The analysis of 16S rRNA
      sequences of the horse, pig, cow, rat, and goose fecal isolates confirm that they
      are members of the genus Methanobrevibacter. They had a high degree of sequence
      similarity (97-98%) with the 16S rRNA gene of M. smithii, indicating that they
      share a common line of descent. The 16S rRNA genes of the horse and pig isolates
      had 99.3% sequence similarity. Sequence analysis of the 16S rRNA gene of the
      sheep fecal isolate showed that it formed a separate line of descent in the genus
      Methanobrevibacter. Genomic DNA reassociation studies indicate that the horse,
      pig, cow, and goose fecal isolates represent at least three new species. The
      horse and pig isolates were the only animal isolates that had > 70% genomic DNA
      reassociation and represent strains of a single species. The cow, goose, and
      sheep isolates had little or no genomic DNA reassociation with M. smithii or with
      each other. The relationship of the rat isolate to the other animal isolates was
      not determined. An evaluation of the relationship of 16S rRNA gene sequence
      similarity and genomic DNA reassociation of Methanobrevibacter and other
      methanogenic archaea indicated that genomic DNA reassociation studies are
      necessary to establish that two methanogenic organisms belong to the same
      species.

PMID- 9560421
TI  - Genetic evidence for a role of thioesterase domains, integrated in or associated
      with peptide synthetases, in non-ribosomal peptide biosynthesis in Bacillus
      subtilis.
AB  - Next to almost all prokaryotic operons encoding peptide synthetases, which are
      involved in the nonribosomal synthesis of peptide antibiotics, distinct genes
      have been detected that encode proteins with strong sequence similarity to type
      II fatty acid thioesterases of vertebrate origin. Furthermore, sequence analysis
      of bacterial and fungal peptide synthetases has revealed a region at the C
      terminal end of modules that are responsible for adding the last amino acid to
      the peptide antibiotics; that region also exhibits significant similarities to
      thioesterases. In order to investigate the function of these putative
      thioesterases in non-ribosomal peptide synthesis of the lipopeptide antibiotic
      surfactin in Bacillus subtilis, srfA fragments encoding the thioesterase domain
      of the surfactin synthetase 3 and the thioesterase-like protein SrfA-TE were
      deleted. This led to a 97 and 84% reduction of the in vivo surfactin production,
      respectively. In the double mutant, however, no surfaction production was
      detectable. These findings demonstrate for the first time that the C-terminal
      thioesterase domains and the SrfA-TE protein are directly involved in
      nonribosomal peptide biosynthesis.

PMID- 9560422
TI  - Urea uptake and urease activity in Corynebacterium glutamicum.
AB  - When Corynebacterium glutamicum is grown with a sufficient nitrogen supply, urea
      crosses the cytoplasmic membrane by passive diffusion. A permeability coefficient
      for urea diffusion of 9 x 10(-7) cm s-1 was determined. Under conditions of
      nitrogen starvation, an energy-dependent urea uptake system was synthesized.
      Carrier-mediated urea transport was catalyzed by a secondary transport system
      linked with proton motive force. With a Km for urea of 9 microM, the affinity of
      this uptake system was much higher than the affinity of urease towards its
      substrate (Km approximately 55 mM urea). The maximum uptake velocity depended on
      the expression level and was relatively low [2-3.5 nmol min-1 (mg dry wt.)-1].

PMID- 9560423
TI  - Characterization of HetR protein turnover in Anabaena sp. PCC 7120.
AB  - The hetR gene plays an important role in heterocyst development and pattern
      formation in heterocystous cyanobacteria. The hetR gene from Anabaena sp. PCC
      7120 was overexpressed in Escherichia coli. Antibodies raised against the
      recombinant HetR protein (rHetR) were used to characterize metabolism of the HetR
      of Anabaena sp. PCC 7120 in vivo. HetR was present at a low level when Anabaena
      sp. PCC 7120 was grown in the presence of combined nitrogen. Shifting from
      nitrogen repletion conditions to nitrogen depletion conditions led to a two fold
      increase of HetR in total cell extracts, and most of HetR was located in
      heterocysts. The amount of HetR in total cellular extracts increased rapidly
      after shifting to nitrogen depletion conditions and reached a maximum level 3 h
      after the shift. Isoelectrofocusing electrophoresis revealed that the native HetR
      had a more acidic isoelectric point than did rHetR. After combined nitrogen was
      added to the nitrogen-depleted cultures, the degradation of HetR depended on
      culture conditions: before heterocysts were fully developed, HetR was rapidly
      degraded; after heterocysts were fully developed, HetR was degraded much more
      slowly. The distribution of HetR in other species of cyanobacteria was also
      studied.

PMID- 9560424
TI  - A periplasmic flavoprotein in Wolinella succinogenes that resembles the fumarate
      reductase of Shewanella putrefaciens.
AB  - During growth with fumarate as the terminal electron transport acceptor and
      either formate or sulfide as the electron donor, Wolinella succinogenes induced a
      peri-plasmic protein (54 kDa) that reacted with an antiserum raised against the
      periplasmic fumarate reductase (Fcc) of Shewanella putrefaciens. However, the
      periplasmic cell fraction of W. succinogenes did not catalyze fumarate reduction
      with viologen radicals. W. succinogenes grown with polysulfide instead of
      fumarate contained much less (< 10%) of the 54-kDa antigen, and the antigen was
      not detectable in nitrate-grown bacteria. The antigen was most likely encoded by
      the fccA gene of W. succinogenes. The antigen was absent from a DeltafccABC
      mutant, and its size is close to that of the protein predicted by fccA. The fccA
      gene probably encodes a pre-protein carrying an N-terminal signal peptide. The
      sequence of the mature FccA (481 residues, 52.4 kDa) is similar (31% identity) to
      that of the C-terminal part (450 residues) of S. putrefaciens fumarate reductase.
      As indicated by Northern blot analysis, fccA is cotranscribed with fccB and fccC.
      The proteins predicted from the fccB and fccC gene sequences represent tetraheme
      cytochromes c. FccB is similar to the N-terminal part (150 residues) of S.
      putrefaciens fumarate reductase, while FccC resembles the tetraheme cytochromes c
      of the NirT/NapC family. The DeltafccABC mutant of W. succinogenes grew with
      fumarate and formate or sulfide, suggesting that the deleted proteins were not
      required for fumarate respiration with either electron donor.

PMID- 9560427
TI  - Two new motile phototrophic consortia: "Chlorochromatium lunatum" and
      "Pelochromatium selenoides" 
AB  - Two new phototrophic consortia, "Chlorochromatium lunatum" and "Pelochromatium
      selenoides", were observed and collected in the hypolimnion of several dimictic
      lakes in Wisconsin and Michigan (USA). The two consortia had the same morphology
      but different pigment composition. The cells of the photosynthetic components of
      the consortia were half-moon-shaped. This morphology was used to differentiate
      them from the previously described motile phototrophic consortia
      "Chlorochromatium aggregatum" and "Pelochromatium roseum". These phototrophic
      cells did not resemble any described unicellular green sulfur bacteria. The
      predominant pigments detected were bacteriochlorophyll d and chlorobactene for
      the green-colored "Clc. lunatum", and bacteriochlorophyll e and isorenieratene
      for the brown-colored "Plc. selenoides". Their pigment compositions and the
      presence of chlorosomes attached to the inner face of the cytoplasmic membrane in
      both kinds of photosynthetic cells confirmed this new half-moon-shaped morphotype
      as a green sulfur bacterium. Both consortia were found thriving in lakes with low
      concentrations of sulfide (< 60 &mgr;M), below the layers of "Clc. aggregatum"
      and "Plc. roseum". The green consortia were observed in lakes where the oxic
      anoxic interface was located at shallow depths (2-7 m), while the brown consortia
      were found at greater depths (8-16 m). The two newly described consortia were
      never detected together at the same depth in any lake.

PMID- 9560426
TI  - Isocitrate dehydrogenase and glyoxylate cycle enzyme activities in Bradyrhizobium
      japonicum under various growth conditions.
AB  - Bradyrhizobium japonicum, the nitrogen-fixing symbiotic partner of soybean, was
      grown on various carbon substrates and assayed for the presence of the glyoxylate
      cycle enzymes, isocitrate lyase and malate synthase. The highest levels of
      isocitrate lyase [165-170 nmol min-1 (mg protein)-1] were found in cells grown on
      acetate or beta-hydroxybutyrate, intermediate activity was found after growth on
      pyruvate or galactose, and very little activity was found in cells grown on
      arabinose, malate, or glycerol. Malate synthase activity was present in arabinose
      and malate-grown cultures and increased by only 50-80% when cells were grown on
      acetate. B. japonicum bacteroids, harvested at four different nodule ages, showed
      very little isocitrate lyase activity, implying that a complete glyoxylate cycle
      is not functional during symbiosis. The apparent Km of isocitrate lyase for D,L
      isocitrate was fourfold higher than that of isocitrate dehydrogenase (61.5 and
      15.5 microM, respectively) in desalted crude extracts from acetate-grown B.
      japonicum. When isocitrate lyase was induced, neither the Vmax nor the D,L
      isocitrate Km of isocitrate dehydrogenase changed, implying that isocitrate
      dehydrogenase is not inhibited by covalent modification to facilitate operation
      of the glyoxylate cycle in B. japonicum.

PMID- 9560425
TI  - Molecular genetic evidence for extracytoplasmic localization of sulfur globules
      in Chromatium vinosum.
AB  - Purple sulfur bacteria store sulfur as intracellular globules enclosed by a
      protein envelope. We cloned the genes sgpA, sgpB, and sgpC, which encode the
      three different proteins that constitute the sulfur globule envelope of
      Chromatium vinosum D (DSMZ 180(T)). Southern hybridization analyses and
      nucleotide sequencing showed that these three genes are not clustered in the same
      operon. All three genes are preceded by sequences resembling sigma70-dependent
      promoters, and hairpin structures typical for rho-independent terminators are
      found immediately downstream of the translational stop codons of sgpA, sgpB, and
      sgpC. Insertional inactivation of sgpA in Chr. vinosum showed that the presence
      of only one of the homologous proteins SgpA and SgpB suffices for formation of
      intact sulfur globules. All three sgp genes encode translation products which -
      when compared to the isolated proteins - carry amino-terminal extensions. These
      extensions meet all requirements for typical signal peptides indicating an
      extracytoplasmic localization of the sulfur globule proteins. A fusion of the
      phoA gene to the sequence encoding the proposed signal peptide of sgpA led to
      high specific alkaline phosphatase activities in Escherichia coli, further
      supporting the envisaged targeting process. Together with electron microscopic
      evidence these results provide strong indication for an extracytoplasmic
      localization of the sulfur globules in Chr. vinosum and probably in other
      Chromatiaceae. Extracytoplasmic formation of stored sulfur could contribute to
      the transmembranous Deltap that drives ATP synthesis and reverse electron flow in
      Chr. vinosum.

PMID- 9560428
TI  - Fractionation of sulfur isotopes during thiosulfate reduction by desulfovibrio
      desulfuricans 
AB  - Sulfur isotope fractionation during reduction of thiosulfate was investigated
      with growing batch cultures of Desulfovibrio desulfuricans CSN (DSM 9104) at 30
      degreesC. The sulfide produced was depleted in 34S by 10 per thousand as compared
      to total thiosulfate sulfur. The depletion was equal to that during sulfate
      reduction under similar conditions. The two sulfur atoms of the thiosulfate
      molecule were affected differently by fractionation. Sulfide produced from
      sulfonate sulfur was depleted by 15.4 per thousand, sulfide produced from sulfane
      sulfur by 5.0 per thousand.

PMID- 9560429
TI  - The rnf gene products in rhodobacter capsulatus play an essential role in
      nitrogen fixation during anaerobic DMSO-dependent growth in the dark 
AB  - The rnf genes in Rhodobacter capsulatus are essential for nitrogen fixation in
      the light. Because R. capsulatus grows readily on N2 in the dark by anaerobic
      respiration with dimethylsulfoxide, the diazotrophic capacities of various
      strains in the dark were examined. No rnf mutants tested grew diazotrophically,
      and a nonpolar fdxN-null mutant showed decreased diazotrophic growth in the dark,
      suggesting that the Rnf and FdxN proteins form the primary electron donor pathway
      to nitrogenase in the dark as well as in the light. Nonphotosynthetic mutants
      lacking the component of cyclic electron transport grew diazotrophically and the
      levels of Rnf proteins were similar to those of the wild-type. These results
      indicate that rnf gene products play an essential role in nitrogen fixation
      without any functional link to the cyclic electron transport system.

PMID- 9560430
TI  - The Tup1-Ssn6 general repressor is involved in repression of IME1 encoding a
      transcriptional activator of meiosis in Saccharomyces cerevisiae.
AB  - Ime1 plays a pivotal role in the initiation of meiosis in a/alpha diploid cells
      of Saccharomyces cerevisiae. In the absence of glucose and nitrogen, IME1
      expression is greater in a/alpha cells than in either a or alpha cells and
      therefore only a/alpha, but not a/a or alpha/alpha, cells are committed to
      sporulation. It is known that IME1 expression is positively regulated by Mck1,
      Rim1, Ime4 and the Swi-Snf complex but other factors may also be involved. In
      addition, Rme1 is assumed to repress IME1 expression. To provide more details of
      the repression of expression of IME1, we have isolated mutants in which the IME1p
      PHO5 fusion gene integrated at the ura3 locus is expressed in alpha cells under
      nutritionally rich conditions. We found that mutations occurred in TUP1, SSN6,
      SIN4 and RGR1, among which TUP1 and SSN6 were identified for the first time as
      negative regulators of IME1 expression. Deletion of the Rme1-binding site from
      the IME1 promoter did not result in activation of the expression of IME1 under
      nutritionally rich conditions, suggesting that Rme1 does not function as a DNA
      binding protein with the Tup1-Ssn6 repression complex. We also demonstrated that
      the 294-bp fragment from nucleotide position -914 to -621 and the 301-bp fragment
      from nucleotide position -1215 to -915 of the IME1 promoter region contain
      elements acting as URS and UAS in TUP1+ and tup1 mutant cells, respectively.
      These findings indicate that IME1 is negatively regulated by the Tup1-Ssn6
      repressor complex through two distinct upstream regions in conjunction with
      unidentified DNA-binding proteins.

PMID- 9560431
TI  - S. pombe sck2+, a second homologue of S. cerevisiae SCH9 in fission yeast,
      encodes a putative protein kinase closely related to PKA in function.
AB  - The Schizosaccharomyces pombe sck2 gene, originally identified as SPAC22E12.14c
      in the genome-sequencing project, encodes a putative protein kinase highly
      similar to Saccharomyces cerevisiae Sch9p and S. pombe Sck1p, both of which can
      suppress loss of cAMP-dependent protein kinase (PKA) if over-produced. Over
      expression of sck2 suppressed typical phenotypes of PKA-defective cells,
      including ectopic mating, slow growth and short cell morphology. Wild-type cells
      over-expressing sck2 behaved like the PKA-hyperactive mutant. Disruption of sck2
      caused no obvious phenotype, but it intensified de-repression for sexual
      development when combined with the disruption of sck1. The pka1 sck1 sck2 triple
      disruptant could grow but only very slowly. Whereas disruption of sck1 enhanced
      the inefficiency of Deltapka1 spores in germination, disruption of sck2 did not.
      These results suggest that the molecular function of Sck2p largely overlaps with
      that of Sck1p, but also that they differ somewhat either quantitatively or
      qualitatively.

PMID- 9560432
TI  - Exogenous inositol and genes responsible for inositol transport are required for
      mating and sporulation in Shizosaccharomyces pombe.
AB  - Fission yeast, Schizosaccharomyces pombe, is a natural inositol auxotroph. We
      show here that the amount of exogenous inositol added to the medium is critical
      for the control of its life cycle. Above growth-limiting concentrations inositol
      stimulates mating and sporulation in minimal medium. The effect of inositol is
      also observed on yeast-extract-medium plates. We selected a mutant, IM49, which
      mates and sporulates only poorly and show that it is defective in inositol
      transport. Its defect is in a gene (itr2) coding for a putative 12 membrane
      spanning protein. The polypeptide contains the two sugar-transport motifs typical
      for hexose transporters and shows good homology to the two Saccharomyces
      cerevisiae inositol transporters. The itr2 gene is essential for cell growth and
      its mRNA level is repressed by glucose. Mutant IM49 is also complemented by a
      multicopy suppressor gene (itr1) which codes for a putative hexose transporter
      with unknown substrate specifity.

PMID- 9560433
TI  - The Kluyveromyces lactis gene KLGSK-3 combines functions which in Saccharomyces
      cerevisiae are performed by MCK1 and MSD1.
AB  - The sequence and characterization of the KlGSK-3 gene in chromosome VI
      [corrected] from Kluyveromyces lactis is presented. The deduced amino-acid
      sequence predicts a protein of 415 amino acids and an Mr of 47 kDa. A computer
      search reveals significant homology to serine/threonine protein kinases closely
      related to members of the GSK-3 subfamily. The Klgsk-3::URA3 disrupted strain is
      unable to grow in glucose at 37 C but KlGSK-3 is not essential for vegetative
      growth at 30 C or 14 C. The KlGSK-3 gene presents the highest homology with the
      Saccharomyces cerevisiae MDS1 gene. Expression studies show an increase of mRNA
      levels caused both by carbon starvation and when diploids are shifted from rich
      to sporulation media. The data reported show that KlGSK-3, like MCK1 from S.
      cerevisiae, is related to glycogen storage.

PMID- 9560434
TI  - Molecular analysis of the LYS2 gene of Candida albicans: homology to peptide
      antibiotic synthetases and the regulation of the alpha-aminoadipate reductase.
AB  - The unique alpha-aminoadipate pathway for lysine biosynthesis is present only in
      fungi and involves eight enzyme steps. alpha-Aminoadipate semialdehyde
      dehydrogenase, commonly called alpha-aminoadipate reductase (AAR), catalyzes the
      conversion of alpha-aminoadipic acid to alpha-aminoadipic semialdehyde by a novel
      mechanism. Two genes, LYS2 and LYS5, encode the heterodimeric enzyme in
      Saccharomyces cerevisiae. The LYS2 gene of Candida albicans was shown to be
      contained in the 4.8-kb insert of the plasmid pCaLYS2. This plasmid complemented
      lys2 mutants of both S. cerevisiae and C. albicans. The S. cerevisiae and C.
      albicans Lys2(+) transformants exhibited 138% and 160% of wild-type AAR activity,
      respectively. The DNA-sequence analysis of the 4.8-kb region in plasmid pCaLYS2
      and a PCR product from genomic DNA which overlapped with the 4.8-kb insert
      revealed a continuous ORF of 4173 nucleotides encoding 1391 amino-acid residues.
      The C. albicans LYS2 ORF exhibited 63.0% identity at the nucleotide level and
      56.2% identity at the amino-acid level to the LYS2 gene of S. cerevisiae. The ORF
      is preceded by consensus sequences for the TATA-, CAAT- and GCN4-box elements. An
      S. cerevesiae-type transcription termination signal is seen in the 3' flanking
      region. The deduced amino-acid sequence revealed a motif for an AMP-binding site
      and also the highly conserved core sequences common to peptide antibiotic
      synthetases. The LYS2 mRNA and alpha-aminoadipate reductase activity were
      repressed to a higher level in YEPD-grown cells than in cells grown in the
      presence of lysine or minimal medium. Additionally, AAR was shown to be feedback
      inhibited by lysine and the lysine analog, thialysine. The results of the present
      report reveal the molecular characteristics of the LYS2 gene of C. albicans, its
      homology to peptide antibiotic synthetases, its divergence from the LYS2 gene of
      S. cerevisiae, and the regulation of AAR in C. albicans.

PMID- 9560435
TI  - Cloning and characterization of the yeast RAD1 homolog gene (mus-38) from
      Neurospora crassa: evidence for involvement in nucleotide excision repair.
AB  - A Neurospora crassa gene encoding a product with homology to the Saccharomyces
      cerevisiae Rad1 nucleotide excision repair (NER) protein was isolated by
      degenerate PCR. The predicted protein consists of 892 amino acids with a
      molecular weight of 100.4 kDa, and 32-37% identity to the XPF/ERCC4 protein
      family. The homolog was mapped to the left arm of linkage group I, the location
      of the mus-38 gene. Subsequently, gene inactivation and complementation studies
      identified the RAD1 homolog as mus-38. Immunological assays showed that the mus
      18 (UV-specific endonuclease) and mus-38 strains have partial and normal UV
      damage excision activities, respectively, but removal of thymine dimers and TC (6
      4) photoproducts is abolished in the mus-18 mus-38 double mutant. The double
      mutant also was synergistically more sensitive to UV than either single mutant.
      The data suggest that mus-38 may participate in a different NER pathway from that
      involving the mus-18 gene.

PMID- 9560437
TI  - Variation in genome organization of the plant pathogenic fungus Colletotrichum
      lindemuthianum.
AB  - The genome structure of Colletotrichum lindemuthianum in a set of diverse
      isolates was investigated using a combination of physical and molecular
      approaches. Flow cytometric measurement of genome size revealed significant
      variation between strains, with the smallest genome representing 59% of the
      largest. Southern-blot profiles of a cloned fungal telomere revealed a total
      chromosome number varying from 9 to 12. Chromosome separations using pulsed-field
      gel electrophoresis (PFGE) showed that these chromosomes belong to two distinct
      size classes: a variable number of small (< 2.5 Mb) polymorphic chromosomes and a
      set of unresolved chromosomes larger than 7 Mb. Two dispersed repeat elements
      were shown to cluster on distinct polymorphic minichromosomes. Single-copy
      flanking sequences from these repeat-containing clones specifically marked
      distinct small chromosomes. These markers were absent in some strains, indicating
      that part of the observed variability in genome organization may be explained by
      the presence or absence, in a given strain, of dispensable genomic regions and/or
      chromosomes.

PMID- 9560436
TI  - Trichoderma reesei prs12 encodes a stress- and unfolded-protein-response
      inducible regulatory subunit of the fungal 26S proteasome.
AB  - We have cloned a gene, prs12, from the filamentous fungus Trichoderma reesei
      which encodes a fungal homologue of the mouse and Drosophila regulatory subunit
      12 of the 26S proteasome (mov34). Sequencing of both a genomic and a cDNA-clone
      predicts a 342-aa protein with high overall identity (56-68 %) to the homologous
      counterparts from human, mammals, Drosophila and Saccharomyces cerevisiae. The
      predicted protein contains several consensus sequences for phosphorylation, three
      of which are conserved in all published Prs12p homologues. Its C-terminus is rich
      in alternating K and E/D, and resembles a potential KEKE-motif. Prs12 exhibits a
      basal level of transcription during normal growth, but its expression is
      significantly increased over 60-120 min under conditions of stress evoked by the
      addition of cadmium ions and hygromycin B. It is also stimulated by the addition
      of tunicamycin and 2-mercaptoethanol, suggesting its regulation by the presence
      of unfolded proteins in the endoplasmic reticulum and by hygromycin B. Consistent
      with this behaviour, motifs in the prs12 5'-upstream sequences show sequence
      homology with the consensus sequences for general stress response, and for an ER
      traffic-response element.

PMID- 9560438
TI  - Inducing the loss of conditionally dispensable chromosomes in Nectria
      haematococca during vegetative growth.
AB  - A procedure for inducing and detecting the loss of conditionally dispensable (CD)
      chromosomes in filamentous fungi during vegetative growth was developed using
      Nectria haematococca mating population VI as a model. CD chromosomes in two
      different isolates of N. haematococca were tagged via integrative transformation
      with a gene conferring resistance to hygromycin B. In each case the
      transformation vector included chromosome-specific DNA in order to direct its
      homologous recombination with the desired chromosome. Chromosome loss was induced
      by exposing tagged isolates to inhibitory concentrations of benomyl either for
      protracted periods of time on solid medium or for short periods of time in liquid
      medium. After exposure to benomyl, isolates that lost the tagged chromosome were
      identified by their loss of resistance to hygromycin B. Electrophoretic
      karyotyping was used to verify that isolates which failed to grow on hygromycin B
      lacked an intact CD chromosome. Ten other chemicals known to interfere with
      mitotic events or cell development in other organisms did not induce CD
      chromosome loss in N. haematococca.

PMID- 9560439
TI  - A ribosomal protein gene cluster is encoded in the mitochondrial DNA of
      Dictyostelium discoideum: UGA termination codons and similarity of gene order to
      Acanthamoeba castellanii.
AB  - We sequenced a region of about 14.5 kb downstream from the ribosomal protein L11
      gene (rpl11) in the mitochondrial DNA (54+/-2 kb) of the cellular slime mold
      Dictyostelium discoideum. Sequence analysis revealed that eleven ribosomal
      protein genes and six open reading frames (ORFs) formed a cluster arranged in the
      order: rpl11-orf189-rps12-rps7-rpl2-rps19-+ ++orf425-orf1740-rpl16-rpl14-orf188-
      rps14-rps8-rpl6-rps13-orf127-orf796. This order was very similar to that of
      homologous genes in Acanthamoeba castellanii mitochondrial DNA. The N-terminal
      region of ORF425 and the C-terminal region of ORF1740 had partial similarities to
      the S3 ribosomal protein of other organisms. The termination codons of rpl16 and
      orf188 were UGA, which has not hitherto been found in genes encoded in D.
      discoideum mitochondrial DNA.

PMID- 9560440
TI  - Protein kinase C mediates the desensitization of CCh-activated nonselective
      cationic current in guinea-pig gastric myocytes.
AB  - The possibility of the protein kinase C (PKC) pathway being a mechanism
      underlying the desensitization of carbachol- (CCh-)activated nonselective
      cationic current (ICCh) was investigated in a study of guinea-pig gastric
      myocytes. Using the conventional whole-cell patch-clamp technique with
      symmetrical CsCl-rich solution in pipette and bath, ICCh was induced by bath
      application of 50 microM CCh. With 0.5 mM EGTA [ethyleneglycol-bis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid] in the pipette solution (0.5 mM
      [EGTA]i), ICCh decayed spontaneously (desensitization of ICCh) to around 20%
      within 10 min. Desensitization of ICCh was significantly attenuated with 2 mM
      [EGTA]i. At a concentration of 20 microM OAG (1-oleoyl-2-acetyl-sn-glycerol), a
      PKC activator, inhibited ICCh at 0.5 mM [EGTA]i but far less at 2 mM [EGTA]i (18%
      and 81% of control, respectively). The same cationic current induced by
      intracellular guanosine-5'-O-(3-thiotriphosphate) (GTP[gamma-S]) was not
      inhibited by OAG with 0.5 mM [EGTA]i. The pretreatment of gastric myocytes with
      PKC inhibitors, either 1 microM chelerythrine or 1 microM peptide inhibitor,
      attenuated the desensitization of ICCh. [Ca2+]i was also measured by single cell
      microfluorometry using fura-2. Under CCh stimulation with 2 mM [EGTA]i, [Ca2+]i
      did not increase above 100 nM while it increased to around 260 nM with 0.5 mM
      [EGTA]i. These results suggest that the desensitization of ICCh is partly due to
      the Ca2+-dependent PKC pathway in guinea-pig gastric myocytes.

PMID- 9560441
TI  - Axial and transverse stiffness measures of cochlear outer hair cells suggest a
      common mechanical basis.
AB  - The function of the hearing organ is based on mechanical processes occurring at
      the cellular level. The mechanical properties of guinea-pig isolated sensory
      cells were investigated using two different techniques. The stiffness of the
      outer hair cells along the longitudinal axis was measured by compressing the cell
      body using stiffness-calibrated quartz fibres. For cells with a mean length of 69
      micron, the mean axial compression stiffness was 1. 1+/-0.8 mN/m (+/-SD). There
      was an inverse relation between stiffness and cell length. The stiffness of the
      cell membrane perpendicular to the longitudinal axis of the sensory cell was
      measured by indenting the cell membrane with a known force. The mean lateral
      indentation stiffness was 3.3+/-1.5 mN/m (+/-SD) for cells with a mean length of
      64 microm. Longer cells were less stiff than short cells. Modelling the hair cell
      as a shell with bending resistance, finite element calculations demonstrated that
      the axial compression stiffness correlated well with the lateral indentation
      stiffness, and that a simple isotropic model is sufficient to explain the
      experimental observations despite the different stress strain states produced by
      the two techniques. The results imply that the two different stiffness properties
      may originate from the same cytoskeletal structures. It is suggested that the
      mechanical properties of the outer hair cells are designed to influence the sound
      induced motion of the reticular lamina. In such a system, stiffness changes of
      the outer hair cell bodies could actively control the efficiency of the
      mechanical coupling between the basilar membrane and the important
      mechanoelectrical transduction sites at the surface of the hearing organ.

PMID- 9560442
TI  - Internalization of urinary trypsin inhibitor in human uterine fibroblasts.
AB  - We have characterized the molecular species and internalization of urinary
      trypsin inhibitor (UTI) in human uterine fibroblasts. Link protein (LP) has
      previously been identified as one of the cell-associated UTI binding proteins.
      The truncated forms of UTI were readily detectable in the cells after incubating
      the cells with purified UTI. Immunoblotting analysis with a panel of domain
      specific antibodies revealed that the UTI species lacked the amino-terminal
      domain of UTI, but contained the carboxyl-terminal domain. We have examined
      whether LP is involved in the UTI internalization in the cells. Internalization
      of 125I-labelled UTI was blocked by the intact UTI, but not by the carboxyl
      terminal domain of UTI. Treatment with a polyclonal antibody to the UTI binding
      domain of LP partially inhibited UTI binding to the cells, but did not
      significantly prevent UTI internalization. In addition, preincubation of the
      cells with hyaluronidase reduced the UTI binding to the cells, but had no effect
      on the rate with which UTI was internalized. These data allow us to conclude that
      there are at least two different mechanisms for internalization of UTI. The major
      one is via unknown UTI receptors in a Ca2+, Mg2+-sensitive manner and another is
      via LP.

PMID- 9560443
TI  - alpha1-adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate
      the Kv1.5 K+ channel expression differentially in cultured newborn rat
      ventricular cells.
AB  - Interest has arisen concerning the importance of alpha-adrenergic function and
      insulin-like growth factor-1 (IGF-1) in cardiac remodelling. The hypothesis that
      these two factors may underlie the regulation of voltage-gated K+ channel
      expression in hypertrophied cardiomyocytes was tested by performing Western blot
      analysis of the Kv1.5 K+ channel alpha-subunit in cultured newborn rat
      ventricular cells. Myocyte size was quantified by surface area and total cell
      protein concentration. Cell exposure to the alpha1-adrenoceptor agonist
      phenylephrine (PE, 20 microM) and IGF-1 (60 ng/ml) for 72 h both induced a
      significant increase of cell size indicating myocyte hypertrophy, which could be
      separately blocked by the protein kinase C inhibitor staurosporine (20 nM) and
      the tyrosine kinase inhibitor genistein (15 microM). Western blots of cell
      proteins prepared from myocyte cultures showed a single protein band at 75 kD
      recognized by the anti-Kv1.5 antibody, and demonstrated a 56% reduction in the
      Kv1. 5 immunoreactive protein level in the PE-treated cell preparations. This
      suppression was not affected by staurosporine, but was remarkably attenuated by
      W7 (20 microM), a selective calmodulin antagonist. In contrast to PE, a 48%
      enhancement of the protein expression of Kv1.5 channel was induced by IGF-1 and
      this stimulation was specifically blocked by genistein. Our findings suggest that
      the differential regulation of cardiac Kv1.5 K+ channel expression can be
      produced by alpha1-adrenoceptor activation and IGF-1 via distinctive signalling
      pathways. Calmodulin-dependent kinase and tyrosine kinase contribute importantly
      to the alpha1-adrenoceptor-mediated decrease and the IGF-1-mediated increase in
      cardiac Kv1.5 K+ channel expression, respectively.

PMID- 9560444
TI  - Different purinergic receptors lead to intracellular calcium increases in
      pancreatic ducts.
AB  - Extracellular adenosine 5'-triphosphate (ATP) has been described to act as a
      regulator in many cells and tissues, including epithelia, and in the
      gastrointestinal tract ATP is one of the substances involved in non-cholinergic
      non-adrenergic control. However, very little is known about the effect of ATP on
      pancreatic ducts, which normally secrete bicarbonate-rich fluid in response to
      secretin. Hence, the aim of our present study was to test the effect of ATP and
      other nucleotides on intracellular Ca2+ activity ([Ca2+]i) of pancreatic ducts,
      and thereby get information about purinergic receptors that might play a role in
      the regulation of pancreatic bicarbonate transport. Native intralobular ducts
      were obtained from rat pancreas and [Ca2+]i in 10-20 cells was measured using the
      fura-2 method. ATP (10(-4) mol/l) evoked a characteristic biphasic Ca2+ transient
      in duct cells. Nucleotides, used to classify the P2 receptors, acted with the
      following potency on the peak Ca2+ in many ducts: uridine 5'-triphosphate (UTP)
      >/= ATP >inosine 5'-triphosphate >/= 2-methylthio-ATP > beta,gamma-methyl-ATP >
      adenosine. However, although the peak [Ca2+]i responses to ATP and UTP were
      similar, the plateau [Ca2+]i was nearly doubled with UTP. Moreover, in about one
      third of the ducts studied, UTP had no effect on cell Ca2+, while the response to
      ATP was normal. In further experiments we found that removal of extracellular
      Mg2+ increased the peak [Ca2+]i evoked in response to ATP. 2'&3'-O-(4
      benzoylbenzoyl) ATP (BzATP) evoked a monophasic and slower increase in [Ca2+]i,
      which was inhibited by removal of extracellular Ca2+, or by addition of 4,4'
      diisothiocyanatostilbene-2, 2'-disulphonic acid (DIDS). Taken together, our data
      indicate that there are two types of purinergic receptors on pancreatic ducts
      through which ATP can act. These are pharmacologically known as P2U and P2Z
      receptors and may correspond to P2Y2 and P2X7 receptors.

PMID- 9560446
TI  - Characterization of ion currents elicited by a stream of fluid during spontaneous
      and ligand-induced chloride current oscillation in Xenopus laevis oocytes.
AB  - During Ca2+-activated C- current oscillations a mechanical deformation of the
      Xenopus laevis oocyte by a fluid stream evokes transient inward currents of high
      amplitude (stream evoked inward current, Ii,st). This current can be observed
      either in native or RNA-injected oocytes expressing ligand-controlled ion
      channels from rat brain. Ii,st reversed at the equilibrium potential of chloride
      and was blocked by 9-anthracene carboxylic acid (2 mM). Power spectral analysis
      of the oscillations did not reveal a correlation between the features of the
      oscillations and the amplitude of Ii,st. Antagonists of stretch-activated cation
      channels [gadolinium (100 microM) and lanthanum (1mM)] did not block Ii,st.
      Calcium channel blockers [cobalt and manganese (10 mM)] did not inhibited Ii,st
      and Ii,st could also be elicited in calcium-free medium. Preloading oocytes with
      pertussis toxin (PTX) for 17 h prevented current oscillations and Ii,st caffeine
      (10 mM), an antagonist of the liberation of calcium from intracellular stores,
      inhibited Ii,st. Our results proride evidence for modulation of the
      mechanosensitivity of chloride currents by activation of intracellular second
      messenger cascades.

PMID- 9560445
TI  - ATP-induced Ca2+ signals in bronchial epithelial cells.
AB  - Ca2+-dependent Cl- secretion in the respiratory tract occurs physiologically or
      under pathophysiological conditions when inflammatory mediators are released. The
      mechanism of intracellular Ca2+ release was investigated in the immortalized
      bronchial epithelial cell line 16HBE14o-. Experiments on both intact and
      permeabilized cells revealed that only inositol 1,4,5-trisphosphate (InsP3)
      receptors and not ryanodine receptors are involved in intracellular Ca2+ release.
      The expression pattern of the three InsP3 receptor isoforms was assessed both at
      the mRNA and at the protein level. The level of expression at the mRNA level was
      type 3 (92.5%) >> type 2 (5.4%) > type 1 (2.1%) and this rank order was also
      observed at the protein level. The ATP-induced Ca2+ signals in the intact cell,
      consisting of abortive Ca2+ spikes or fully developed [Ca2+] rises and
      intracellular Ca2+ waves, were indicative of positive feedback of Ca2+ on the
      InsP3 receptors. Low Ca2+ concentrations stimulated and high Ca2+ concentrations
      inhibited InsP3-induced Ca2+ release in permeabilized 16HBE14o- cells. We
      localized a cytosolic Ca2+-binding site between amino acid residues 2077 and 2101
      in the type-2 InsP3 receptor and between amino acids 2030 and 2050 in the type-3
      InsP3 receptor by expressing the respective parts of these receptors as
      glutathione S-transferase fusion proteins in bacteria. We conclude that the InsP3
      receptor isoforms expressed in 16HBE14o- cells (mainly type-3 and type-2) are
      stimulated by Ca2+ and that this phenomenon contributes to the ATP-induced Ca2+
      signals in intact 16HBE14o- cells.

PMID- 9560447
TI  - Agonist-independent inactivation and agonist-induced desensitization of the G
      protein-activated K+ channel (GIRK) in Xenopus oocytes.
AB  - The G-protein-activated K+ channels of the GIRK (Kir 3) family are activated by
      Gbetagamma subunits of heterotrimeric Gi/Go proteins. Atrial GIRK currents evoked
      by acetylcholine (ACh)1 via muscarinic m2 receptors (m2R) display prominent
      desensitization. We studied desensitization of basal and ACh-evoked whole-cell
      GIRK currents in Xenopus oocytes. In the absence of receptor and/or agonist, the
      basal GIRK activity showed inactivation which was prominent when the preparation
      was bathed in a low-Na+, high-K+ extracellular solution (96 mM [K+]out and 2 mM
      [Na+]out) but did not occur in a normal physiological solution. Ion substitution
      experiments showed that this basal, agonist-independent inactivation was caused
      by the decrease in [Na+]out rather than by the increased [K+]out. We hypothesize
      that it reflects a depletion of intracellular Na+. ACh-evoked GIRK currents
      desensitized faster than the basal ones. The agonist-induced desensitization was
      present when the preparation was bathed in all solutions tested, independently of
      [Na+]out. A protein kinase C (PKC) activator inhibited the GIRK currents both in
      high and low [Na+]out, apparently mimicking agonist-induced desensitization;
      however, a potent serine/threonine protein kinase blocker, staurosporine, blocked
      only a minor part of desensitization. We conclude that basal inactivation and
      agonist-induced desensitization are separate processes, the former caused by
      changes in Na+ concentrations, and the latter by unknown factor(s) with only a
      minor contribution of PKC.

PMID- 9560448
TI  - Store depletion triggers the calcium release-activated calcium current (ICRAC) in
      macrovascular endothelial cells: a comparison with Jurkat and embryonic kidney
      cell lines.
AB  - In endothelial cells, different types of Ca2+ conductances have been described,
      but none of them has been clearly identified as ICRAC, the Ca2+ release-activated
      Ca2+ current originally described in mast and lymphoma cells. Here we show that
      in bovine pulmonary artery endothelial cells (CPAE) depletion of intracellular
      Ca2+ stores by inositol 1,4,5-trisphosphate (InsP3), Ca2+ ionophores and Ca2+
      pump inhibitors activates a Ca2+-selective conductance in the presence of the
      Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid (BAPTA).
      The current shows inward rectification, a highly positive reversal potential and
      is blocked by micromolar concentrations of La3+. The conditions used in studies
      of endothelial cells were also employed in those of HEK-293, an embryonic kidney
      cell line commonly used to express putative store-operated channels, and Jurkat
      cells, the reference cell model. Similar to CPAE, HEK cells also have an ICRAC
      like current. At 0 mV holding potential the estimated current density is -0.1 and
      -0.2 pA/pF in CPAE and HEK cells respectively, i.e. 15 and 30% of that measured
      in Jurkat cells. As shown in studies of Jurkat cells, larger Na+ currents are
      detectable in CPAE and HEK cells following store depletion in Ca2+- and Mg2+-free
      medium. The current carried by Na+ ions is similarly blocked by micromolar La3+,
      is inwardly rectifying and has a positive reversal potential.

PMID- 9560449
TI  - Separation of calcium channel current components in mouse chromaffin cells
      superfused with low- and high-barium solutions.
AB  - This study was carried out to characterize the set of voltage-dependent Ca2+
      channel subtypes expressed by mouse adrenal chromaffin cells superfused with
      solutions containing low (2 mM) or high (10 mM) Ba2+ concentrations. Using 50-ms
      test pulses at 0 mV from a holding potential of -80 mV, averaged peak current in
      10 mM Ba2+ was around 1 nA, and in 2 mM Ba2+ 0.36 nA. When using 2 mM Ba2+ as the
      charge carrier, nifedipine (3 microM) blocked IBa by 40-45%. omega-Conotoxin GVIA
      (1 microM) caused 26% inhibition, while omega-conotoxin MVIIC (3 microM) produced
      a 48% blockade. At low concentrations (20 nM), omega-agatoxin IVA caused 5-15% of
      current inhibition, while 2 microM gave rise to a 35-40% blockade. In 10 mM Ba2+,
      the blocking effects of nifedipine (40%) and omega-conotoxin GVIA (25%) were
      similar to those seen in 2 mM Ba2+. In contrast, blockade by omega-conotoxin
      MVIIC was markedly reduced in 10 mM Ba2+ (20-25%) as compared to 10 mM Ba2+
      (48%). The blocking actions of omega-agatoxin IVA (2 microM) were also slowed
      down in 10 mM Ba2+, though the final blockade was unaffected. In 2 mM Ba2+, IBa
      was quickly inhibited by over 94% with combined nifedipine + omega-conotoxin
      MVIIC + omega-conotoxin GVIA; in 10 mM Ba2+, IBa was blocked by 70% with this
      combination. The data suggest that mouse chromaffin cells express L-type (40%) as
      well as non-L-type (60%) high-threshold voltage-dependent Ca2+ channels. The
      current carried by non-L-type Ca2+ channels consists of about 25% N-type and 35%
      P/Q-type; P-type channels, if anything, are poorly expressed. The data also
      indicate that the fraction of current blocked by omega-conotoxin MVIIC and omega
      agatoxin IVA might considerably change as a function of the Ba2+ concentration of
      the extracellular solution; taking this fact into consideration, it seems that a
      residual R-type current is not expressed in mouse chromaffin cells.

PMID- 9560450
TI  - No evidence for cell-to-cell coupling in rat colonic crypts: studies with Lucifer
      Yellow and with photobleaching.
AB  - Epithelial cells of exocrine glands (pancreas, lacrimal glands, salivary glands,
      sweat glands and gastric glands) are intimately linked together by gap junctions.
      Due to this close junctional coupling exocrine secretion occurs as the well
      concerted effort of a cell population. Colonic crypts have, on the one hand,
      anatomical and functional properties resembling those of exocrine glands (mostly
      crypt base cells) and, on the other hand, properties of absorbing cells (mostly
      surface cells). In the mid-crypt, depending on the functional status, absorption
      and secretion can occur. The present study was aimed at examining whether rat
      distal colonic crypt cells co-ordinate their functional status by cell-to-cell
      coupling. Two types of measurements were performed: as an independent assessment
      of cell viability the membrane voltage (Vm) was measured with the fast whole-cell
      patch-clamp technique; to investigate cellular coupling simultaneously Lucifer
      Yellow (LY) (mol. wt. 443) distribution was visualized using digital video
      imaging. LY (500 micromol/l) was included into the patch pipette filling
      solution. The recorded Vm was -73.4+/-2.3 mV in crypt base cells (n=15), -63.7+/
      2.1 mV in mid-crypt cells (n=17) and -52.3+/-2. 9 mV in crypt surface cells. All
      cells tested reversibly responded to carbachol (100 micromol/l) with a persistent
      hyperpolarization, as previously shown. Activation of Cl- secretion by elevation
      of the cAMP concentration with forskolin (5 micromol/l) led to a reversible
      depolarization. Throughout the duration of each individual experiment [mean
      experimental time in basal cells: 18.3+/-2.5 min (n=15), in mid-crypt cells:
      19.6+/-3.4 min (n=17) and in crypt surface cells: 11.7+/-3.4 min (n=13)] LY dye
      distribution was solely confined to the patched cell. In addition bleaching of
      calcein fluorescence in laser scan microscopy was not followed by dye back
      diffusion, whereas this was clearly the case in pancreatic acini (n=5). These
      data indicate that colonic crypt cells are not coupled by gap junctions under
      resting conditions or in the presence of secretagogues.

PMID- 9560451
TI  - Acetylcholine-activated chloride current in the T-84 colonic cell line.
AB  - The stimulation of epithelial chloride secretion by hormones and
      neurotransmitters involves the activation of apical membrane chloride channels.
      The regulation of chloride current by acetylcholine in the T-84 colonic cell line
      was investigated using single-channel patch-clamp techniques. Treatment with
      carbachol resulted in the stimulation of transient chloride currents in 18 of 32
      previously quiescent patches. Lack of resolvable single-channel openings suggests
      that single-channel conductance is less than 5-pS. Of 18 responsive patches, 4
      showed multiple current oscillations. Treatment of the cells with AlF4- activated
      sustained chloride currents, suggesting that G proteins are involved. In excised
      patches, chloride current was markedly sensitive to free Ca2+ concentrations
      between 500 and 1000 nM. Time-dependent activation and inactivation of chloride
      current occurred at +60 and -60 mV. These results indicate that the chloride
      channels responsible for cholinergic activation of chloride conductance in the T
      84 colonic cell line are members of the very low conductance family of chloride
      channels.

PMID- 9560452
TI  - Single-channel analysis of fast transient outward K+ currents in frog skeletal
      muscle.
AB  - The patch-clamp method was employed to examine the voltage-dependent gating
      mechanism of A-type K+ channels, which generate the transient outward K+ currents
      described previously in a study of vesicles derived from the sarcolemma of frog
      skeletal muscle. Channels were activated by depolarizing pulses. There is
      evidence for non-random grouping of records with channel openings and blank
      records when depolarizations were repeated at brief intervals, suggesting a slow
      process similar to slow inactivation. Binomial analysis was consistent with
      independent behaviour of the channels. Ensemble average currents obtained from
      multichannel patches had kinetics similar to those of the macroscopic A-type K+
      current, IA. The rate of activation, fitted to n4 kinetics, was fast and voltage
      dependent. The rate of inactivation had an exponential time course with a voltage
      independent time constant. The mean open time and the probability of a channel
      being open increased with depolarization. The histograms of latency to first
      opening revealed the presence of more than two voltage-dependent closed states.
      Channel openings occurred in bursts and the closed-time histograms could be
      fitted by the sum of two or three exponentials. These results suggest a gating
      scheme with at least three closed states, probably two open states, and two
      inactivated states.

PMID- 9560453
TI  - Effects of cyclopiazonic acid on Ca2+ regulation by the sarcoplasmic reticulum in
      saponin-permeabilized skeletal muscle fibres.
AB  - The effects of the sarcoplasmic reticulum (SR) Ca2+ pump inhibitor cyclopiazonic
      acid (CPA) were studied in saponin-permeabilized frog skeletal muscle fibres.
      Release of Ca2+ from the SR was triggered by brief (2 s) applications of 40 mM
      caffeine at 2-min intervals. Changes in [Ca2+] within the fibre were monitored
      continuously using Fura-2 fluorescence. At a bathing [Ca2+] of 100 nM,
      introduction of 20 microM CPA induced a slow release of Ca2+ from the SR. The
      following one to two caffeine-induced Ca2+ transients were markedly increased in
      amplitude and duration. Thereafter, the caffeine-induced Ca2+ transients
      decreased progressively and were barely detectable 6-7 min after introduction of
      CPA. However, increasing the bathing [Ca2+] or increasing the Ca2+ loading period
      resulted in a partial recovery of the caffeine-induced Ca2+ transients,
      suggesting that pump inhibition is incomplete, even in the presence of 100 microM
      CPA. The slow Ca2+ efflux induced by CPA was insensitive to ryanodine, but absent
      following abolition of SR Ca2+ pump activity by ATP withdrawal. These results
      suggest that the caffeine-induced Ca2+ transient reflects a balance between
      efflux via the SR Ca2+ channel and reuptake by the Ca pump. Ca2+ release upon
      addition of CPA may result from inhibition of SR Ca2+ uptake, which reveals a
      tonic Ca2+ efflux that is independent of the Ca2+ release channels.

PMID- 9560454
TI  - Effect of dehydration on apical Na+-H+ exchange activity and Na+-dependent sugar
      transport in brush-border membrane vesicles isolated from chick intestine.
AB  - The current work examines the effect of 4 days of water deprivation on Na+-H+
      exchange and Na+-sugar cotransport systems in brush-border membrane vesicles
      isolated from either the jejunum, ileum or the colon of the chick. Apical Na+-H+
      exchange activity was evaluated by measuring the pH-gradient-dependent Na+
      uptake. The contribution of the Na+-H+ exchangers NHE2 and NHE3 to total Na+-H+
      exchange activity was evaluated from their sensitivity to the amiloride-related
      drug HOE694. Dehydration increased plasma aldosterone levels from 12 to 70 pg/ml
      and also the activities of both Na+-H+ exchange and Na+-dependent sugar transport
      in the three intestinal regions tested. Na+-independent sugar transport was not
      modified by 4 days of water deprivation. In the ileum and colon the increase in
      Na+-H+ exchange activity was due to an increase in NHE2 activity, whereas in the
      jejunum it was due to an increase in both NHE2 and NHE3. Since we have previously
      reported that chronic Na+ depletion increases plasma aldosterone levels and NHE2
      activity in ileum and colon, decreased small and large intestine Na+-sugar
      cotransport activity and had no effect on jejunal apical Na+-H+ exchange
      activity, it can be concluded that: (1) aldosterone does not regulate intestinal
      Na+-dependent sugar transport, and (2) the regulation of jejunal Na+-H+ exchange
      activity differs from that of either the ileum or the colon.

PMID- 9560455
TI  - Characterisation of the effects of robustoxin, the lethal neurotoxin from the
      Sydney funnel-web spider Atrax robustus, on sodium channel activation and
      inactivation.
AB  - The present study investigates the actions of robustoxin (atracotoxin-Ar1)
      purified from the venom of the male Sydney funnel-web spider Atrax robustus on
      sodium channel gating. Using whole-cell patch-clamp techniques the study assessed
      the actions of robustoxin on tetrodotoxin-resistant (TTX-R) and tetrodotoxin
      sensitive (TTX-S) sodium currents in rat dorsal root ganglion cells. Similar to
      the closely related funnel-web spider toxin versutoxin (delta-atracotoxin-Hv1)
      from Hadronyche versuta, robustoxin had no effect on TTX-R sodium currents but
      exerted potent effects on TTX-S sodium currents. The main action of robustoxin
      was a concentration-dependent slowing or removal of TTX-S sodium current
      inactivation. This steady-state current was maintained during long-lasting
      depolarisations at all test potentials. Robustoxin (30 nM) also caused a 13-mV
      hyperpolarising shift in the voltage midpoint of steady-state sodium channel
      inactivation (h infinity) leading to a reduced peak current at a holding
      potential of -80 mV. Moreover there was a steady-state or non-inactivating
      component present (18% of maximal sodium current) at prepulse potentials that
      normally inactivate all TTX-S sodium channels (more depolarised than -40 mV). In
      addition robustoxin produced a significant increase in the repriming kinetics of
      the sodium channel when channels returned to the resting state following
      activation. This increase in the rate of recovery of sodium current appears to
      explain the use-dependent effects on peak sodium current amplitude at high
      stimulation frequencies. Finally 30 nM robustoxin caused an 11-mV hyperpolarising
      shift in the voltage dependence of the channel but did not markedly modify tail
      current kinetics. These actions suggest that robustoxin inhibits conversion of
      the open state to the inactivated state of TTX-S sodium channels, thus allowing a
      fraction of the sodium current to remain at membrane potentials at which
      inactivation is normally complete. Given the recent reclassification of funnel
      web spider toxins as atracotoxins, robustoxin should henceforth be known as delta
      atracotoxin-Ar1 to reflect this main action on sodium channel inactivation. These
      present results further support the hypothesis that funnel-web spider toxins
      interact with neurotoxin receptor site 3 to slow channel inactivation in a manner
      similar to that of alpha-scorpion and sea anemone toxins.

PMID- 9560457
TI  - The role of cytosolic Ca2+ in the secretion of NaCl in isolated in vitro perfused
      rectal gland tubules of Squalus acanthias.
AB  - In many exocrine glands cytosolic Ca2+ ([Ca2+]i) plays a pivotal role in
      stimulation-secretion coupling. In the rectal gland of the dogfish Squalus
      acanthias this appears not to be the case and it is believed that secretion is
      mainly controlled by the Cl- conductance of the luminal membrane. We have
      examined this question in a study of isolated in vitro perfused rectal gland
      tubules (RGT). Three types of measurements were performed: (1) measurements of
      [Ca2+]i by the fura-2 technique; (2) measurements of transepithelial electrical
      parameters, i.e. transepithelial voltage (Vte), transepithelial resistance (Rte),
      the equivalent short-circuit current (Isc) and the voltage across the basolateral
      membrane (Vbl), and (3) whole-cell patch-clamp measurements of cellular voltage
      (Vm), conductance (Gm) and membrane capacitance (Cm). The data indicates that
      carbachol (CCH) increases [Ca2+]i by increasing store release and Ca2+ influx.
      Other agonists, producing cytosolic cAMP, also increased [Ca2+] by enhancing Ca2+
      influx. CCH hyperpolarized these cells and enhanced Gm significantly. The effect
      of CCH on Vte and Isc was most marked under control conditions and disappeared in
      RGT otherwise stimulated by agonists that lead to cAMP production. It is
      concluded that [Ca2+]i plays a major role in the stimulation of NaCl secretion in
      RGT by enhancing the basolateral K+ conductance. cAMP-producing agonists enhance
      [Ca2+]i by increased Ca2+ influx. CCH releases Ca2+ from respective stores. CCH,
      unlike the cAMP-producing agonists, only increases basolateral K+ conductance. It
      modulates secretion especially under conditions in which the cAMP pathway is not
      fully activated.

PMID- 9560456
TI  - Tyrosine kinase inhibitors suppress N-type and T-type Ca2+ channel currents in
      NG108-15 cells.
AB  - Modulation of Ca2+ channel activity by protein kinases constitutes one of the
      major mechanisms regulating neuronal functions. Here, we explored the possible
      modulation of neuronal Ca2+ channels by protein tyrosine kinases (PTKs). To this
      end, the effects of PTK inhibitors on whole-cell Ba2+ currents (IBa) through
      voltage-gated Ca2+ channels were analysed in differentiated NG108-15
      neuroblastoma x glioma hybrid cells. Genistein suppressed IBa in a concentration
      dependent fashion (IC50 = 22 microM). Although daidzein, an analogue of genistein
      that is devoid of PTK inhibitory activity, also suppressed IBa, we estimated that
      specific PTK inhibition by genistein reduced IBa amplitude by 30%. In addition,
      lavendustin A (20 microM) and herbimycin A (20 microM), two other distinct PTK
      inhibitors, depressed IBa by 22% and 20%, respectively. Genistein suppressed N
      type and T-type currents, sparing L-type current, and its effect was independent
      of G protein activation. The results suggest that the activity of neuronal Ca2+
      channels can be modulated by PTKs, opening the possibility that some of the
      functions of PTKs in the nervous system are mediated by Ca2+ channel modulation.

PMID- 9560458
TI  - Quantitative analysis of dual whole-cell voltage-clamp determination of gap
      junctional conductance.
AB  - The dual whole-cell voltage-clamp technique is used widely for determination of
      kinetics and conductance of gap junctions. The use of this technique may,
      however, occasion to considerable errors. We have analysed the errors in steady
      state junctional conductance measurements under different experimental
      conditions. The errors in measured junctional conductance induced by series
      resistance alone, and by series resistance in combination with membrane
      resistance, were quantified both theoretically and experimentally, on equivalent
      resistive circuits with known resistance values in a dual voltage-clamp setup. We
      present and analyse a method that accounts for series resistance and membrane
      resistance in the determination of true junctional conductance. This method
      requires that series resistance is determined during the experiment, and involves
      some calculations to determine membrane resistance. We demonstrate that
      correction for both membrane and series resistance reduces the error in measured
      junctional conductance to near zero, even when membrane resistances on both sides
      of the gap junction are as low as 20 MOmega and the (true) junctional conductance
      is as high as 100 nS.

PMID- 9560460
TI  - Investigating the relaxation, following diazo-2 laser flash photolysis, of a
      skinned trabecular preparation from SHR hypertrophied left ventricle.
AB  - Rat models of cardiac hypertrophy are characterised by a shift in left
      ventricular myosin isoform from V1 (adult) to V3 (foetal), the latter being
      associated with a slowing of the acto-myosin ATPase rate. The aim of this study
      was to examine hypertrophy effects on relaxation by investigating a chemically
      skinned cardiac preparation from the SHR, where all the cellular membranes are
      rendered non-functional allowing the myofibrils to be studied in isolation. On
      comparison, following photolysis of the photolabile caged Ca2+ chelator diazo-2,
      it can be seen that the SHR fibres relax at a slower rate than their age-matched
      WKY counterparts. We suggest that, since the thin filament regulatory proteins
      seem not to be affected by cardiac hypertrophy in the rat, this result can be
      attributed to the shift in left ventricular myosin isoforms. The reduced
      relaxation rate in the SHR could be the result of a slowing of the dissociation
      of actin and myosin during the cross-bridge cycle. These results have previously
      been published in abstract form [1].

PMID- 9560459
TI  - Modulation by extracellular and intracellular iodide of volume-activated Cl-
      current in HeLa cells.
AB  - The patch-clamp technique was used to study the effect of extracellular and
      intracellular iodide on the properties of the volume-activated anion current in
      HeLa cells. Upon hypotonic challenge, HeLa cells responded by activating an
      outwardly rectifying Cl- current. Replacement of extracellular Cl- by I-, a more
      permeable anion, increased the peak outward and inward current, reduced the
      magnitude of deactivation observed at depolarized potentials and shifted the half
      maximal (V0.5) deactivation voltage towards more positive values. On the other
      hand, when internal Cl- was replaced by I- the volume-activated current was not
      observed in normal, Cl--rich hypotonic extracellular solution. However, switching
      to a hypotonic extracellular solution containing a mixture of Cl- and I- resulted
      in the activation of the volume-sensitive current. Furthermore, once the current
      was activated, I- could be excluded from the external solution without
      significantly affecting the current properties. These results suggest that the
      permeant anion plays a crucial role in the gating mechanism of the volume
      activated Cl- current, influencing the swelling-dependent activation and the
      voltage-dependent deactivation processes.

PMID- 9560461
TI  - Cytoskeletal mechanisms of axon outgrowth and pathfinding.
AB  - The use of modern techniques involving gene transfer and functional knock-out
      strategies has lead to new concepts of the way in which cytoskeletal elements
      interact to produce the unique morphologies of neurons. This review presents
      these concepts and discusses their implications for neuronal development,
      especially with respect to the role of microtubules, microfilaments, and
      neurofilaments.

PMID- 9560462
TI  - The significance of the isoforms of plasma membrane calcium ATPase.
AB  - The plasma membrane calcium ATPase (PMCA) or Ca2+ pump transports Ca2+ ions out
      of the cells, by using the energy stored in ATP. It is essential in the control
      of Ca2+ concentration in the cytosol. The plasma membrane Ca2+ pump has been
      found in all mammalian cells and is encoded by four independent genes. The number
      of possible isoforms is further increased by alternative splicing at two
      independent sites; transcripts for more than 20 isoforms have been detected. The
      PMCA isoforms, in particular some of their alternatively spliced isoforms, have
      been shown to bind calmodulin with different affinity. The activity of these
      alternatively spliced pumps is possibly differently regulated by kinase-mediated
      phosphorylation. A short summary of recent work on the properties of the PMCA
      isoforms is presented here.

PMID- 9560463
TI  - Galactosphingolipids and axono-glial interaction in myelin of the central nervous
      system.
AB  - The myelin of central and peripheral nervous system of UDP-galactose-ceramide
      galactosyltransferase deficient mice (cgt-/-) is completely depleted of its major
      lipid constituents, galactocerebrosides and sulfatides. The deficiency of these
      glycolipids affects the biophysical properties of the myelin sheath and causes
      the loss of the rapid saltatory conduction velocity of myelinated axons. With the
      onset of myelination, null mutant cgt-/- mice develop fatal neurological defects.
      CNS and PNS analysis of cgt-/- mice revealed (1) hypomyelination of axons of the
      spinal cord and optic nerves, but no apoptosis of oligodendrocytes, (2) redundant
      myelin in younger mice leading to vacuolated nerve fibers in cgt-/- mice, (3) the
      occurrence of multiple myelinated CNS axons, and (4) severely distorted lateral
      loops in CNS paranodes. The loss of saltatory conduction is not associated with a
      randomization of voltage-gated sodium channels in the axolemma of PNS fibers. We
      conclude that cerebrosides (GalC) and sulfatides (sGalC) play a major role in CNS
      axono-glial interaction. A close axono-glial contact is not a prerequisite for
      the spiraling and compaction process of myelin. Axonal sodium channels remain
      clustered at the nodes of Ranvier independent of the change in the physical
      properties of myelin membrane devoid of galactosphingolipids. Increased
      intracellular concentrations of free ceramides do not trigger apoptosis of
      oligodendrocytes.

PMID- 9560464
TI  - Calcium-binding proteins in the retina of a calbindin-null mutant mouse.
AB  - Calcium-binding proteins are abundantly expressed in many neurons of mammalian
      retinae. Their physiological roles are, however, largely unknown. This is
      particularly true for calcium-modulating proteins ("calcium buffers") such as
      calbindin D28k. Here, we have studied retinae of wildtype (+/+) and calbindin
      null mutant (-/-) mice by using immunocytochemical methods. Although calbindin
      immunoreactivity was completely absent in the calbindin (-/-) retinae, those
      cells that express the protein in wildtype retinae, such as horizontal cells,
      were still present and appeared normal. This was verified by immunostaining
      horizontal cells for various neurofilament proteins. In order to assess whether
      other calcium-binding proteins are upregulated in the mutant mouse and may thus
      compensate for the loss of calbindin, mouse retinae were also immunolabeled for
      parvalbumin, calretinin, and a calmodulin-like protein (CALP). In no instance
      could a change in the expression pattern of these proteins be detected by
      immunocytochemical methods. Thus, our results show that calbindin is not required
      for the maintenance of the light-microscopic structure of the differentiated
      retina and suggest roles for this protein in retinal function.

PMID- 9560465
TI  - Immunolocalization of a putative unconventional myosin on the surface of motile
      mitochondria in locust photoreceptors.
AB  - Light stimulation of locust (Schistocerca gregaria) photoreceptors results in an
      actin-dependent translocation of mitochondria towards the photoreceptive
      microvilli and an antagonistic movement of endoplasmic reticulum towards the cell
      body. Using immunocytochemical techniques, we have tried to identify myosin-like
      motors that may drive the light-induced organelle motility. A monoclonal antibody
      against the motor domain of Acanthamoeba myosin identifies a prominent 110-kDa
      protein on Western blots of locust retina. Cross-reactivity with two polyclonal
      anti-myosin antibodies and a monoclonal anti-myosin-I-antibody, together with ATP
      dependent binding to actin filaments, provides evidence that the 110-kDa protein
      is an unconventional myosin. By indirect immunofluorescence, the 110-kDa protein
      has been localized to both photoreceptors and pigment cells within the retina. In
      the photoreceptor cells, the 110-kDa protein is bound to the surface of
      mitochondria. This putative unconventional myosin may thus be a motor protein
      involved in the light-induced translocation of mitochondria in photoreceptors.

PMID- 9560466
TI  - Neuronal differentiation is accompanied by NSP-C expression.
AB  - Neuroendocrine-specific protein (NSP) reticulons are expressed in neural and
      neuroendocrine tissues and cell cultures derived therefrom, while most other cell
      types lack NSP-reticulons. Three major subtypes have been identified so far,
      designated NSP-A, NSP-B, and NSP-C. We have investigated the correlation between
      the degree of neuronal differentiation, determined by morphological and
      biochemical criteria, and NSP-reticulon subtype expression. For this purpose,
      several human neuroblastoma cell lines, exhibiting different degrees of neuronal
      differentiation, were examined immuno(cyto)chemically. It became obvious that the
      expression of NSP-C, as detected by immunofluorescence microscopy and Western
      blotting, is most prominent in cell lines with a high degree of neuronal
      differentiation, such as LA-N-5. Such highly differentiated cells also express
      other neural and neuroendocrine markers, such as neural cell adhesion molecule
      (NCAM), neurofilament proteins, synaptophysin, and chromogranin. NSP-A was
      observed in all cell lines to a different extent. However, no clear correlation
      was observed with the degree of neuronal differentiation as defined by other
      neuronal and neuroendocrine markers or morphology. NSP-B could not be detected.
      The induction of neuronal differentiation with nerve growth factor, dbcAMP, and
      retinoic acid in the rat pheochromocytoma cell line PC12 and the human
      teratocarcinoma cell line hNT2, respectively, induced the expression of NSP-A and
      NSP-C in these cell lines parallel to the induction of neurofilament protein
      expression. It is concluded that NSP-C expression, in particular, is strongly
      correlated with neuronal differentiation.

PMID- 9560467
TI  - Partial sequencing of Reissner's fiber glycoprotein I (RF-Gly I).
AB  - The bulk of the secretion of the subcommissural organ is formed by glycoproteins
      that appear to be derived from two precursor forms of 540 and 320 kDa. Upon
      release into the ventricle, these glycoproteins aggregate to form Reissner's
      fiber. We report the isolation of three cDNA clones from a cDNA library prepared
      from bovine subcommissural organ RNA, by using an anti-Reissner's fiber serum for
      immunoscreening. Inserts of 0.7, 1.2, and 2.5 kb were amplified by the polymerase
      chain reaction, subcloned into pUC18 vector, and sequenced. Although restriction
      mapping of the three inserts initially suggested that all of them were derived
      from the same mRNA, sequence analysis showed that a short non-homologous region
      was present in the 0.7-kb insert when compared with the 1. 2-kb and 2.5-kb
      inserts, suggesting that they corresponded to two different, although highly
      homologous, mRNAs. Northern analyses showed a single mRNA species of
      approximately 9.5 kb present in the subcommissural organ and missing in the
      choroid plexus, brain cortex, and liver. In situ hybridization confirmed that the
      expression of the RNA was restricted to cells of the bovine subcommissural organ.
      Polyclonal antibodies raised against a synthetic peptide, whose amino-acid
      sequence was deduced from the 2.5-kb cDNA, reacted specifically with the bovine
      and rat subcommissural organ-Reissner's fiber complex. In immunoblots of bovine
      subcommissural organ, this antibody revealed the precursor 540-kDa form and its
      putative processed form of 450 kDa. It is concluded that the cloned cDNA encodes
      for the major constitutive glycoprotein of Reissner's fiber, here designated as
      RF-Gly I. The sequenced region of RF-Gly I displays a high degree of homology
      with some regions of the von Willebrand factor and certain mucins; it also
      displays two motifs homologous with repeats present in proteins of the spondin
      family and other proteins. A core sequence of the RF-Gly I repeats suggests that
      this molecule displays protein-binding properties.

PMID- 9560468
TI  - Distribution of pro-opiomelanocortin and its peptide end products in the brain
      and hypophysis of the aquatic toad, Xenopus laevis.
AB  - Using in situ hybridization with a pro-opiomelanocortin (POMC)-mRNA probe and
      immunocytochemistry with antisera to POMC and to various POMC-derived peptides,
      it is shown that melanotrope cells in the pars intermedia of the hypophysis of
      the South African aquatic toad Xenopus laevis contain POMC, alpha-melanophore
      stimulating hormone (alpha-MSH), gamma-MSH, acetylated and non-acetylated
      endorphins and adrenocorticotropic hormone (ACTH). With the exception of gamma
      MSH, these peptides are also found in the corticotrope cells in the rostral pars
      distalis. In the Xenopus brain, neuronal cell bodies in the ventral hypothalamic
      nucleus express POMC, alpha-MSH, gamma-MSH, non-acetylated endorphins and ACTH,
      neurones in the anterior preoptic area reveal POMC, alpha-MSH, gamma-MSH and non
      acetylated endorphin, neurones in the suprachiasmatic nucleus contain alpha-MSH,
      non-acetylated endorphin and ACTH and neurones in the posterior tubercle show
      alpha-MSH, non-acetylated endorphin and ACTH immunoreactivities. In the locus
      coeruleus POMC and ACTH coexist, whereas alpha-MSH and non-acetylated endorphin
      occur together in the nucleus accumbens, the striatum and the nucleus of the
      paraventricular organ. Finally, alpha-MSH alone is present in the olfactory bulb,
      the medial septum, the medial and lateral parts of the amygdala, the ventromedial
      and posterior thalamic nuclei, the optic tectum and the anteroventral tegmental
      nucleus, and non-acetylated endorphin alone appears in the epiphysis. It is
      suggested that neurones that form POMC-derived peptides may play a direct or
      indirect role in the control of POMC-producing hypophyseal cells and/or in the
      physiological processes these endocrine cells regulate. This idea is supported by
      the fact that the suprachiasmatic nucleus and the locus coeruleus, both involved
      in melanotrope cell control, show POMC and POMC-peptide expression. A possible
      involvement in melanotrope and/or corticotrope control of the anterior preoptic
      and ventral hypothalamic nuclei, which both express POMC and various POMC-derived
      peptides, deserves future attention.

PMID- 9560470
TI  - Visualization of interstitial cells of Cajal in the mouse colon by vital
      staining.
AB  - Interstitial cells of Cajal (ICCs) are believed to be a major element in
      generating the spontaneous rhythm of the gastrointestinal tract. A prominent
      problem in the study of these cells has been the difficulty in observing them in
      intact tissues. We used the lipophilic dye DiI to stain ICCs in the submucosal
      circular muscle border of freshly dissected mouse colon. The placement of small
      DiI crystals in this area resulted in the labeling of ICC-like cells. Two main
      morphological cell types, viz., bipolar and multipolar, were noted. Bipolar cells
      had two primary processes emerging from the poles of an elongated soma. The mean
      length of these processes was 78.7 microm. These cells constituted 42.3% of the
      sample (n=105). Multipolar cells (54.3% of total) had a less elongated soma and
      extended 3-6 main processes whose mean length was 56.3 microm. These processes
      showed no preferred direction. The length of the primary processes of bipolar
      cells was 40% greater than that of multipolar cells (P<0.02). Three cells (2.9%)
      had only one primary process. The DiI stain could be converted into a stable
      electron-opaque product. Electron-microscopic observations showed that these
      cells had the typical appearance of ICCs reported in previous studies. This
      staining method should be useful for physiological investigations of ICCs in
      gastrointestinal tissues.

PMID- 9560469
TI  - Two differing salmon GnRH precursor mRNAs are co-expressed in the brain of
      sockeye salmon.
AB  - The localization of two salmon-type gonadotropin-releasing hormone (sGnRH)
      precursors, pro-sGnRH-I (short type) and pro-sGnRH-II (long type), was
      investigated by using in situ hybridization techniques in the brain of the
      landlocked sockeye salmon, Oncorhynchus nerka. We used 30-mer oligonucleotide
      probes complementary to pro-sGnRH-I and pro-sGnRH-II cDNA. No significant
      differences were observed in the localization of sGnRH neurons expressing pro
      sGnRH-I and pro-sGnRH-II mRNAs; both were expressed in the olfactory nerve, the
      olfactory bulbs, the regions between the olfactory bulb and telencephalon, the
      ventral telencephalon, the preoptic area, and the hypothalamus. Almost all sGnRH
      neurons examined co-expressed both precursors. The expression of two sGnRH
      precursors in the same neuron and the wide distribution of such neurons in the
      brain suggest that there are no functional differences between the two
      precursors.

PMID- 9560471
TI  - Some neurohistochemical properties of nerve elements in myenteric plexus of
      rabbit ileum: similarities and dissimilarities to the rodent pattern.
AB  - Enteric neurons have distinct neurochemical codings in each species. The basal
      tone of the gastrointestinal tract of the rabbit is low and produces neurally
      evoked pendular movements. Therefore, it might have an innervation pattern
      different from that of other laboratory animals. We have characterised myenteric
      neuron populations in rabbit ileum with neurochemical markers that are known to
      be associated with distinct cell types and/or fibre systems in the myenteric
      plexus. The density of nerve cells estimated with the NADH-diaphorase technique
      was about 2500 cells/cm2 and most, if not all, neurons contained microtubule
      associated protein 2. NADPH-diaphorase-positive cells were numerous. One cell
      type was large and emitted long straight processes, whereas small cells bore thin
      filamentous dendrites. Neurons immunoreactive for 28-kDa calcium-binding protein
      were rare. Over 70% of them had very strongly labelled lamellar dendrites. Their
      axons were beaded and formed pericellular baskets around unstained somata. We
      found very few small tyrosine-hydroxylase-positive cells. The fibre network in
      the plexus was very strong; the axons formed many pericellular baskets. In double
      labelling studies, no co-localisation was revealed between the 28-kDa calcium
      binding protein and NADPH-diaphorase. Some fibres containing 28-kDa calcium
      binding protein formed only a few contacts on somata of NADPH-diaphorase-positive
      cells. None of the NADPH-diaphorase-labelled cells were found to be stained for
      tyrosine hydroxylase. Tyrosine-hydroxylase-positive fibres rarely made
      pericellular baskets on the surface of NADPH-diaphorase-positive somata. Strongly
      immunolabelled pericellular baskets were never observed around NADPH-diaphorase
      positive cell somata. The results suggest that myenteric neurons in rabbit
      comprise distinct and characteristic neurochemical properties that are different
      from the rodent pattern. Therefore, the explanation of the motility pattern of
      rabbit intestine can be approached on a chemical neuroanatomical basis.

PMID- 9560472
TI  - Nitric oxide synthase (NOS) in mouse skeletal muscle development and
      differentiated myoblasts.
AB  - The neuronal isoform of nitric oxide synthase (nNOS, termed also NOS-I) is
      expressed in normal adult skeletal muscle, suggesting important functions for NO
      in muscle biology. However, the expression and subcellular localization of NOS in
      muscle development and myoblast differentiation are largely unknown. In the
      present study, NOS was immunolocalized with isoform-specific antibodies in
      developing muscle and in differentiated myoblast cultures (mouse C2C12) together
      with histochemical NADPH-dependent diaphorase activity that is blocked by
      specific NOS inhibitors and therefore designated as NOS-associated diaphorase
      activity (NOSaD). Western blot analysis revealed immunoreactive bands for NOS-I
      III in lysates from perinatal and adult muscle tissue and C2C12-myotubes that
      comigrated with prototypical proteins. In embryonic skeletal muscle, but not in
      adult myofibers, diffuse cytosolic staining and lack of sarcolemmal NOSaD
      activity and NOS-I immunoreaction were evident. In both myoblasts and fusioned
      myotubes, NOSaD and NOS isoforms I-III colocalize in the cytosol. Additionally,
      members of the sarcolemmal dystrophin-glycoprotein complex (i.e., dystrophin,
      adhalin, beta1-dystroglycan) immunolocalize in the cytosol of differentiating
      myoblasts, whereas anti-dystrophin and anti-beta1-dystroglycan clearly delineate
      the sarcolemma in myotubes. Thus, expression of NOS isoforms I-III and NOSaD is
      cytosolic in fusion-competent myoblasts during myotube formation in vitro.
      Interaction of NOSaD/NOS-I with the sarcolemmal dystrophin-complex known from
      mature myofibers is apparently lacking in prenatal muscle development and
      differentiating myoblasts. Localization of NOS isoforms thus characterized in
      myogenic cultures may help further to investigate regulated NO formation in
      muscle cells in vitro.

PMID- 9560473
TI  - Human and hamster procathepsin D, although equally tagged with mannose-6
      phosphate, are differentially targeted to lysosomes in transfected BHK cells.
AB  - BHK cells transfected with human cathepsin D (CD) cDNA normally segregate the
      autologous hamster cathepsin D while secreting a large proportion of the human
      proenzyme. In the present work, we have utilized these transfectants to examine
      to what extent the mannose-6-phosphate-dependent pathway for lysosomal enzyme
      segregation contributes to the differential sorting of human and hamster CD. We
      report that, in recipient control BHK cells, the rate of mannose-6-phosphate
      dependent endocytosis of human procathepsin D secreted by transfected BHK cells
      is lower than that of hamster procathepsin D and much lower than that of human
      arylsulphatase A. The missorted human enzyme bears phosphorylated
      oligosaccharides and most of its phosphate residues are "uncovered", like the
      autologous enzyme. Thus, despite both the Golgi-associated modifications of
      oligosaccharides, i.e. the phosphorylation of mannose and the uncovering of
      mannose-6-phosphate residues, which proceed on human and hamster procathepsin D
      with comparable efficiency, only the latter is accurately packaged into
      lysosomes. Ammonium chloride partially affects the lysosomal targeting of
      cathepsin D in control BHK cells, whereas in transfected cells, this drug
      strongly inhibits the maturation of human procathepsin D and slightly enhances
      its secretion. These data indicate that: (1) over-expression of a lysosomal
      protein does not saturate the Golgi-associated reactions leading to the synthesis
      of mannose-6-phosphate; (2) a portion of cathepsin D is targeted independently of
      mannose-6-phosphate receptors in the transfected BHK cells; and (3) whichever
      mechanism for lysosomal delivery of autologous procathepsin D is involved, this
      is not saturated by the high rate of expression of human cathepsin D.

PMID- 9560475
TI  - Differential in situ expression of alpha2(XI) collagen mRNA isoforms in the
      developing mouse.
AB  - Type XI collagen is an essential structural component of the extracellular matrix
      of cartilage and plays a role in collagen fibril formation and skeletal
      morphogenesis. The expression of all three type XI collagen genes is not
      restricted to cartilage. In addition, alternative exon usage seems to increase
      the structural diversity and functional potential of type XI collagen during
      development. In order to investigate type XI collagen expression during
      development, we have examined alpha2(XI) and alpha1(XI) collagen genes by in situ
      hybridization in mice. Transcripts of the alpha2(XI) collagen gene were first
      detected in the notochord of mouse embryos after 11.5 days of gestation.
      Subsequently, alpha2(XI) mRNA was mainly found in the cartilaginous tissues of
      the developing limbs and axial skeleton together with transcripts of the
      alpha1(XI) gene. The alpha2(XI) transcripts seemed to be alternatively spliced
      isoforms lacking exons 6-8, which code for an acidic domain. Expression of
      alpha2(XI) outside the cartilage was relatively restricted, whereas expression of
      the alpha1(XI) gene was widespread. However, expression of alpha2(XI) transcripts
      containing exons 6-8 was found in non-chondrogenic tissues, including the
      calvarium and periosteum where intramembranous ossification occurs. These results
      indicate that alpha2(XI) mRNA isoforms are differentially expressed in various
      tissues during development. In addition, alpha2(XI) mRNA isoforms containing
      alternative exons are present in osteogenic cells, and their expression may be
      closely related to the formation of bone or cartilage.

PMID- 9560474
TI  - Distribution of murine mannose receptor expression from early embryogenesis
      through to adulthood.
AB  - The mannose receptor is a 175-kDa transmembrane glycoprotein that appears to be
      expressed on the surface of terminally differentiated macrophages and Langerhans
      cells. The ectodomain of the mannose receptor has eight carbohydrate recognition
      domains. The receptor recognizes the patterns of sugars that adorn a wide array
      of bacteria, parasites, yeast, fungi, and mannosylated ligands. Clearance studies
      in whole animals have localized radiolabeled ligands, such as mannosylated bovine
      serum albumen, not only to macrophages, but also to liver sinusoidal endothelial
      cells. Hitherto, there has been no comprehensive analysis of expression of the
      mannose receptor in embryonic and adult mouse tissues. In this study, we have
      undertaken a systematic survey of the expression of the mannose receptor from
      early embryogenesis through to adulthood. The mannose receptor is expressed on
      tissue macrophages throughout the adult mouse as expected. However, the mannose
      receptor is first observed on embryonic day 9 on cells that line blood island
      vessel walls in the yolk sac. The mannose receptor is localized on sinusoidal
      endothelial cells in embryonic liver by embryonic day 11 and in bone marrow at
      embryonic day 17. This pattern persists in these organs throughout embryogenesis
      into adulthood when sinusoidal endothelial cells of lymph nodes also express the
      mannose receptor. The receptor is also found on lymphatic endothelial cells of
      small intestine. In contrast, sinusoids of spleen and thymus do not express
      mannose receptor antigen. This study demonstrates that the mannose receptor is
      expressed on tissue macrophages and on subsets of vascular and lymphatic
      endothelial cells. Thus, the mannose receptor maybe a marker of the so-called
      reticuloendothelial system.

PMID- 9560477
TI  - Chymotrypsin gene expression in rat peripheral organs.
AB  - Prior studies have revealed the presence of chymotrypsinlike protease in
      peripheral organs, although no definitive evidence for the synthesis of this
      enzyme in tissue other than the pancreas is available. In an attempt to detect
      chymotrypsinogen mRNA in peripheral organs, a fragment of the pancreatic
      chymotrypsin mRNA from rat was amplified using PCR. The sequence was identified
      as a portion of the rat chymotrypsin B gene overlapping exon 5 through exon 7. It
      was subcloned into the pGEM-4Z vector and used as a template for the vitro
      transcription of an antisense riboprobe. Using ribonuclease protection and
      Northern blot analyses, chymotrypsin mRNA was detected in the rat pancreas,
      stomach, duodenum, ovary, and spleen. Monoclonal and polyclonal antisera against
      chymotrypsin detected chymotrypsinlike immunoreactivity in rat and human
      pancreas, rat stomach, duodenum and jejunum. Electrophoresis and immunoblotting
      revealed chymotrypsin-chymotrypsinogen bands (25-29 kDa) in the stomach and
      duodenum. Synthesis of a potent protease such as chymotrypsin in tissue other
      than pancreas is significant, suggesting a potential physiological and/or
      pathological role in these tissues.

PMID- 9560476
TI  - Distribution of endoglin in early human development reveals high levels on
      endocardial cushion tissue mesenchyme during valve formation.
AB  - Endoglin is a component of the receptor complex for transforming growth factor
      (TGF)-beta1 and TGF-beta3. We analysed its expression by immunohistochemistry in
      human embryos at 4-8 weeks of gestation and in hearts ranging from 4-13 weeks
      old. We compared endoglin distribution with that of TGF-beta receptors type I
      (TbetaR-I), type II (TbetaR-II) and betaglycan. Endoglin was found on endothelial
      cells in all tissues examined, consistent with its expression in adult blood
      vessels. TbetaR-I, TbetaR-II and betaglycan were observed on most cell types and
      had an overall similar pattern of distribution. Endoglin was detected on the
      endocardium as early as 4 weeks, but was absent from myocardium. It was present
      at high levels on the endocardial cushion tissue mesenchyme from 5-8 weeks'
      gestation, during heart septation and valve formation, and subsequently decreased
      as the valves matured. Endoglin expression in heart extracts was confirmed by
      Western blot analysis. TbetaR-I, TbetaR-II and betaglycan were mostly found on
      cardiac myocytes, but were detectable at low levels on endocardium. They were
      expressed transiently on cushion mesenchyme, albeit at much lower levels than
      endoglin. All four components of the TGF-beta receptor complex were detected by
      RT-PCR in embryonic heart. Thus transient up-regulation of the components of the
      TGF-beta receptor complex, and particulartly of endoglin, is associated with
      heart septation and valve formation during early human development.

PMID- 9560478
TI  - Establishment of oral mucosa phenotype in vitro in correlation to epithelial
      anchorage.
AB  - Cell-matrix interactions and the ordered deposition of basement membrane (BM)
      components are of major importance for the maintenance of tissue homeostasis in
      complex epithelia. This aspect was studied in vitro in a coculture system
      designed as an oral mucosa model. As crucial epithelial features the kinetics of
      proliferation, expression of site-specific keratins as well as integrin patterns
      in correlation to synthesis of BM components were assessed by
      immunohistochemistry and in situ hybridization. Comparison with non-cornified
      gingiva as tissue of origin revealed different stages of epithelial development,
      eventually leading to complete reconstruction within a time frame of 1-3 weeks.
      First, the initial activated stage up to 1 week was characterized by (a) high
      keratinocyte proliferation, (b) extended expression of the basal cell-specific
      keratin K5 and (c) a patchy pattern of the differentiation-specific keratins K4
      and K13. Second, after 2 weeks the improvement of histoarchitecture correlated to
      (a) predominant K5 expression in the basal and (b) extension of K4 and K13 within
      the suprabasal cell compartment, (c) high expression of integrins alpha3 beta1
      and alpha6 beta4 including their ligand laminin-5 and (d) accumulating deposition
      of basement membrane components. Third, virtually complete tissue normalization
      at 3 weeks was indicated by (a) restriction of K5 to the basal cell area, (b)
      regular suprabasal localization of K4 and K13, (c) polarization of integrins to
      basal and parabasal cells and (d) linear codistribution of collagen IV,
      "classical" laminin (-1 or -10) and laminin-5 underneath the basal cells. Thus,
      these organotypic cocultures represent relevant equivalents for non-keratinized
      oral mucosa with typical gingival differentiation features and in addition
      suitable models for preclinical trials such as prospective dental material
      testing.

PMID- 9560479
TI  - Edema formation in the rat larynx.
AB  - In the rat larynx, plasma exudation and edema formation were studied by light and
      electron microscopy after i.v. injections of the mast cell activator compound
      48/80, substance P, and capsaicin. The morphological effects of substance P and
      capsaicin on connective tissue mast cells in vivo were also examined. Of the
      drugs tested, only compound 48/80 degranulated the connective tissue mast cells.
      All drugs induced a subepithelial plasma exudation in the subglottic region, with
      edema in the lamina propria and widened intraepithelial intercellular spaces,
      though the tight junction regions seemed intact. In the epiglottis, 10 min after
      compound 48/80 injection, there was edema in the lamina propria on the lingual
      side, with an intact and tight epithelial lining. No morphological sign of edema
      was found in the epiglottis after injection of substance P or capsaicin. The
      pronounced effect found in the epiglottic region after compound 48/80 injection
      was due to the release of mediators such as histamine and 5-hydroxytryptamine
      from the connective tissue mast cells. This study supports the belief that
      substance P in vivo mediates an increased vascular permeability by a direct
      effect on the blood vessels - a mechanism distinct from mast cell degranulation.

PMID- 9560480
TI  - Cutaneous glands of male and female impalas (Aepyceros melampus): seasonal
      activity changes and secretory mechanisms.
AB  - The cutaneous glands of the forehead and the metatarsus were studied by
      histological and histochemical methods and electron microscopy in adult male and
      female impalas in various seasons of the year. All glandular areas consist of
      apocrine and holocrine glands, which, however, occur in different proportions.
      Our findings in the apocrine gland cells suggest (1) the synthesis and exocytosis
      of a glycoproteinaceous secretory product stored in secretory granules, (2)
      typical apocrine secretion of the transformed apical cytoplasm, and (3)
      transepithelial fluid transport. The Golgi apparatus and apical membrane have
      binding sites for several lectins (PNA, HPA, RCA I, WGA). Cytokeratins 7, 14 and
      19 are expressed at various intracellular localizations, suggesting an active
      role in the secretory mechanisms. The glands of the male forehead show marked
      seasonal changes in activity that are correlated with the main phases of the
      reproductive cycle, with the highest cellular activity occurring during the rut
      in April/May. The female forehead glands are only moderately developed and do not
      undergo seasonal changes. The metatarsal glands are of equal size in males and
      females and show no seasonal changes in activity. This study supports the
      hypothesis that (1) forehead glands in the male have a signaling role in the rut
      and (2) the metatarsal glands have a more general, probably social role
      maintaining and restoring contact between herd members.

PMID- 9560481
TI  - Uptake of lithium carmine by sinusoidal endothelial and Kupffer cells of the rat
      liver: new insights into the classical vital staining and the reticulo
      endothelial system.
AB  - Sinusoidal cells in the rat liver were studied in vivo and in vitro using the
      original vital staining with lithium carmine, which has contributed much to the
      development of the concept of the reticulo-endothelial system.
      Immunohistochemical and electron-microscopic studies revealed that the dye
      incorporating cells were sinusoidal endothelial cells, Kupffer cells, and
      monocytes. The endothelial cells took up much more dye than did the Kupffer cells
      and bulged largely into the sinusoidal lumen. Electron microscopy revealed that
      small particles of lithium carmine were associated with coated vesicles of
      endothelial cells and ruffled membranes of Kupffer cells. In the endothelial
      cells, these particles were present in various concentrations within vacuolated
      structures and condensed in the lysosomes forming large aggregates of lithium
      carmine lumps. These lumps showed crystalline structures, within which the size
      of the individual particle was up to 30 nm in width and 50 nm in length. A few
      endothelial cells containing abundant dye underwent degeneration, and some were
      taken up by Kupffer cells. Liver endothelial cells isolated from lithium carmine
      administered rats endocytosed fluorescence-labeled collagen. Isolated endothelial
      cells from normal rat liver, when cultured with lithium carmine, did not take up
      any dye, and their endocytosis of formaldehyde-treated albumin was inhibited dose
      dependently. We conclude that in the liver, endothelial cells, but not Kupffer
      cells, predominantly take up lithium carmine. Furthermore, we propose the
      existence of a generalized cell system based on its vital staining capacity.

PMID- 9560482
TI  - Increased functional load on mouse kidney proximal tubule epithelial cells causes
      changes in nucleolar 3-D architecture.
AB  - Ultrastructural 3-D analysis of nucleolar architecture and Ag-NOR protein
      distribution in mouse kidney-cortex proximal-tubule epithelium has been
      performed. A principal scheme of structural changes of the nucleolus and
      organization of its components during the intensification of pre-rRNA synthesis
      (dynamic model of a nucleolus) based on computer spatial modelling has been
      advanced. According to the nucleolar composition, three groups of cells, which
      differ from each other by rRNA synthesis, are defined in normal kidney. Most
      nephron proximal-section cells (about 52%) are characterized by lower activity of
      RNA synthesis. Such kind of cells are defined as group I (nucleolar diameter 0.7
      1.5 microm) and always contain resting, ring-shaped or close to ring-shaped dense
      nucleoli, which have 2 or 3 fibrillar centers. Nucleoli of group II cells (about
      37%, nucleolar diameter 1.5-2.5 microm) have a higher level of activity, contain
      4-7 fibrillar centers, and their structural organization is close to reticulated
      forms due to the first indications of vacuolar network (identified as
      prereticulated nucleoli). The most active cells of group III (about 11%,
      nucleolar diameter 2.5-3.5 microm) include cells with typical reticulated
      nucleoli with a well expressed vacuolar network and numerous fibrillar centers
      (18-22). Increased functional load of the epithelium caused by unilateral
      nephrectomy and diuretic (4-chlor-H [2-furylmethyl] 5-sulphamyl-antranic acid)
      injection changed the proportion of the different cell groups: group I decreased
      (about 25%), whereas groups II and III increased (about 8% and 17%,
      respectively). The increase of nucleolar activity first causes a deformation of
      the individual fibrillar centers as well as complication and growth of their
      surface. Further, a progressive fragmentation of the fibrillar centers and the
      growth of their total volume is observed. The complication and growth of the
      total volume of Ag-positive zones is another indication of the nucleolar
      activation. The vacuolar system develops by a gradual fusion of small isolated
      cavities into a united vacuolar network. Nucleoli with 2-7 fibrillar centers are
      considered to be intermediate forms reflecting successive stages of its
      activation or inactivation: from the resting ring-shaped nucleolus via transient
      stages of increasing functional activity to the active reticulated nucleoli and
      vice versa. The observed differences in the nucleolar ultrastructure are regarded
      as evidence of the functional heterogeneity of cell populations within one
      functional segment of nephron.

PMID- 9560484
TI  - MR angiography: basic principles and theory.
AB  - The most commonly used MR angiography techniques are categorized as time-of
      flight, phase-contrast, or contrast-enhanced methods. When the basic principles
      of the various MR angiographic methods are understood, the techniques can be used
      to achieve high-quality angiograms. This article describes the physical
      principles and theory of some of the most widely used MR angiographic methods.

PMID- 9560483
TI  - Immunocytochemical alterations in the intra-acrosomal antigen MN7 during
      epididymal maturation of guinea pig spermatozoa.
AB  - We have previously shown that a 90-kDa intra-acrosomal antigen, MN7, is
      restricted to the anterior acrosomal region of mouse, rat, and hamster
      spermatozoa. The present study has examined the localization and the behavior of
      MN7 during sperm maturation in the epididymis of the guinea pig by immunoelectron
      microscopy. MN7 showed not only a specific localization in the apical segment of
      the guinea pig sperm acrosome, but also a distinct alteration during maturation,
      as follows. MN7 was exclusively found both at the dorsal matrix and on the outer
      acrosome membrane (OAM)/matrix-associated materials in the apical segment. MN7
      was initially distributed throughout the electron-lucent dorsal matrix in
      immature sperm but, during maturation, became more restricted to the spherical
      bodies within the electron-lucent area. MN7 on OAM/matrix-associated materials
      was first distributed along the ventral margin and the small area posterior to
      the dorsal matrix but, during maturation, disappeared from the ventral margin and
      became restricted to the dorsal region. These results indicate that MN7 is a good
      tool for studying the stepwise maturation of epididymal spermatozoa.

PMID- 9560485
TI  - Contrast-enhanced MR angiography: theory and optimization.
AB  - It is now possible to perform contrast arteriography safely and rapidly by taking
      advantage of gadolinium contrast agents and three-dimensional MR imaging.
      Although the development of this approach to arteriography is in its infancy, the
      image quality already rivals conventional arteriography. As we continue to
      develop this technique by taking advantage of more pulse sequence tricks,
      improving hardware, and improving contrast agents, the field of vascular imaging
      will undoubtedly be transformed. This article discusses the fundamental concepts
      underlying this approach to angiography.

PMID- 9560486
TI  - MR angiography of the aortic arch vessels and upper extremities.
AB  - MR angiography of the aortic arch vessels and upper extremities is a noninvasive
      alternative to conventional catheter angiography without the risks of stroke or
      the potential toxicity of iodinated contrast. The use of optimized, breath hold
      gadolinium-enhanced three-dimensional MR angiography provides excellent image
      quality with the capability of display options not available with conventional
      angiography. This article demonstrates the utility of this new technique in the
      diagnosis of congenital and acquired conditions of the supraaortic vascular
      system.

PMID- 9560487
TI  - MR angiography of the thoracic aorta.
AB  - MR angiography is a powerful tool in evaluating the complete spectrum of
      congenital and acquired diseases of the thoracic aorta. The use of gadolinium
      chelates in conjunction with rapid three-dimensional sequences performed with
      breath holding provides robust image quality with multiple display options. As a
      result of technological advances in hardware, software, and pulse sequence
      implementation combined with innovative use of contrast agents, MR angiography is
      poised to replace conventional catheter angiography of the thoracic aorta for
      many indications.

PMID- 9560488
TI  - MR angiography of the abdominal aorta.
AB  - MR angiography has become a powerful tool for the examination of abdominal aortic
      pathology, including aortic aneurysm, dissection, and occlusion. This article
      reviews the techniques, indications, and imaging findings obtained from MR
      angiography of the abdominal aorta. In addition, the role of MR angiography
      relative to existing modalities is discussed.

PMID- 9560489
TI  - Mesenteric occlusive disease.
AB  - Using contrast-enhanced MR angiography, cine phase contrast MR imaging, and flow
      independent T2 measurements, MR imaging can provide both morphologic information
      about the degree of stenosis of the mesenteric vessels and quantitative
      functional information about blood flow and blood oxygen saturation in these
      vessels. The combination of these techniques can potentially revolutionize the
      diagnosis and post-treatment assessments of both acute and chronic mesenteric
      occlusive disease.

PMID- 9560490
TI  - Renal MR angiography.
AB  - Three-dimensional gadolinium MR angiography (3D-Gd-MRA) accurately visualizes the
      renal arteries with almost no degradation from inplane saturation or motion
      artifacts. The diagnostic accuracy for detecting and grading of renal artery
      stenosis, as well as the assessment of other vascular pathology, approaches that
      of conventional x-ray angiography. For the renovascular system, this technique
      requires precise contrast media bolus timing since multiple successively
      enhancing structures are present. Details on performing renal MR angiography,
      strategies for image analysis, and examples of common renal vascular pathology
      are reviewed. The 3D-Gd-MRA protocol can be easily combined with other MR imaging
      techniques to provide a comprehensive assessment of the hemodynamic and
      functional significance of renal artery stenosis.

PMID- 9560491
TI  - MR angiography of the aortoiliac and femoropopliteal vessels.
AB  - The variety of MR angiography strategies can be applied to the evaluation of
      vascular disease in the aortoiliac and femoropopliteal vessels. When used
      appropriately, a combination of these strategies can be offered to patients with
      peripheral vascular disease as a safe and effective alternative to conventional
      angiography for planning treatment options. This article presents the clinical
      issues, MR techniques, and the results of relevant studies in a detailed manner
      pertinent to accomplishing diagnostic MR angiography in the aortoiliac and
      femoropopliteal segments.

PMID- 9560492
TI  - MR angiography of the peripheral vessels.
AB  - MR angiography of the inflow vessels has undergone dramatic change in the past
      few years; the advent of ultra fast gradient echo pulse sequences combined with
      the gadolinium chelate bolus technique has supplanted earlier methods. However,
      owing to the highly variable flow velocities and inconsistent rate of vessel
      opacification encountered in the outflow vessels, two-dimensional time-of-flight
      MR angiography remains the workhorse of the distal vasculature.

PMID- 9560493
TI  - Body MR angiography: a surgeon's perspective.
AB  - This article addresses the indications for surgical procedures and the anatomic
      relationships that must be imaged to effectively plan surgical intervention.
      Treatment and imaging of aortic aneurysm, aortic dissection, splanchnic artery
      aneurysms, renal artery disease, and arterial disease of the lower extremities
      are reviewed.

PMID- 9560494
TI  - MR angiography of the thoracic, abdominal, and extremity venous system.
AB  - MR angiography is a useful clinical tool for noninvasive evaluation of the
      abdominal, thoracic, and peripheral venous system. A variety of MR techniques are
      available, although two-dimensional time-of-flight is used most commonly. MR
      imaging of the venous system is less hindered by technical limitations and
      artifacts commonly encountered with imaging of the arterial system. This article
      reviews the most commonly used techniques and their clinical application.

PMID- 9560495
TI  - Branchiogenic carcinomas: do they exist?
AB  - The existence of branchiogenic carcinomas is questioned in this review, which
      also discusses the different possibilities in an adult patient who presents with
      a cystic swelling in the upper lateral aspect of the neck. Most cases of
      branchiogenic carcinomas reported in the literature may actually have been
      secondary metastatic lesions from an occult tonsillar carcinoma. We will also
      discuss the different features of cystic metastasis that distinguish them from
      solid metastasis, and explain why oropharyngeal carcinomas with cystic neck
      metastasis should be in a separate category from other head and neck cancers.

PMID- 9560496
TI  - Minimizing the risk of penetrating injury to surgical staff in the operating
      theatre: towards sharp-free surgery.
AB  - Conventional surgery carries a significant risk of inadvertent injury to members
      of the scrub team. Although minor injury is common and usually no more than
      unpleasant, serious consequences may occur. Modifications in technique together
      with the application of modern instrumentation may reduce the risks of sharp
      injury substantially. The techniques and technology available in the conventional
      open surgery setting are reviewed.

PMID- 9560497
TI  - A randomized controlled trial of double-versus single-gloving in vascular
      surgery.
AB  - With the increasing incidence of hepatitis B and HIV, and the increasing
      awareness of the risk and prevalence of hepatitis C, it is becoming even more
      necessary to adopt stricter policies to safeguard personnel and to reduce the
      risk of transmission. Previous studies have shown a need for eye protection,
      protective clothing and the use of double-gloving during operative or
      interventional procedures. The risk of infection is much less with unbroken skin
      and conversely more likely when hollow needles are used. Arguments against the
      routine use of double-gloving include the loss of dexterity and the discomfort
      incurred, and the potential loss of dexterity that might theoretically result in
      more rather than fewer needle-stick injuries.

PMID- 9560498
TI  - Screening for diabetes on a vascular ward: lessons from an audit.
AB  - Owing to the high prevalence of diabetes mellitus in patients with peripheral
      arterial disease, screening for this disorder is necessary on a vascular ward.
      Our current practice of random plasma glucose (RPG) testing on every admission
      was reviewed. This test, although crude, excludes diabetes if the cutoff level is
      set as low as 6.0 mmol/L. A total of 36% of our patients had an abnormal result,
      but this was not further acted upon. A further 19% had no test result recorded at
      all. This practice is inadequate and has resulted in the following
      implementations: (1) every patient with clinical evidence of arterial disease
      should have their RPG level measured; (2) patients with a level > 6.0 mmol/L
      should have a fasting plasma glucose level estimated; and (3) patients with an
      abnormal fasting plasma glucose level should be referred to the diabetic clinic.

PMID- 9560499
TI  - Prospective audit of 200 patients undergoing laparoscopic inguinal hernia repair
      with follow-up from 1 to 4 years.
AB  - The results of 215 laparoscopic transabdominal pre-peritoneal inguinal hernia
      repairs are reported with a follow-up of 1-4 years (median 2.5 years). The
      patients" age range was 17-85 (median 59 years). Three recurrences occurred in
      the first 75 repairs, where a 12 x 7 cm mesh was used. There has been no
      recurrence in the subsequent 140 repairs where a larger 15 x 10 cm mesh was used
      for the repair. A total of 5% of patients developed urinary retention after the
      operation and a further 13% developed minor complications. The procedure was
      remarkably pain-free, with 25% requiring no analgesia after the operation and 67%
      requiring no analgesia after discharge from hospital. There was a rapid return to
      normal activity, with 55% driving within 1 week of the operation and 85% within 2
      weeks. Sixty per cent returned to work within 2 weeks of the operation and 69%
      within 3 weeks. Forty-two of the patients had undergone a previous open hernia
      repair and 93% of these preferred the laparoscopic repair as there was less post
      operative pain and a quicker recovery. The results show that laparoscopic hernia
      repair is remarkably pain-free, allows a rapid return to normal activity and has
      a low recurrence rate when a 15 x 10 cm mesh is used.

PMID- 9560500
TI  - The effect of a dedicated emergency theatre facility on emergency operating
      patterns.
AB  - Following the introduction of a dedicated 24-hour emergency theatre facility in a
      500-bed district general hospital, the total amount of emergency general surgery
      performed after 22.00 hours has been reduced from 37.2 to 13.1%, with a
      concomitant increase in emergency day-time operating from 22.1 to 51.2%. The
      majority of the workload was previously performed by the junior grades, and this
      has remained unchanged. Operative experience has not been diminished with the
      reduction in night-time surgery, and senior supervision has been enhanced. There
      has been no significant difference in mortality or morbidity with the changes in
      operating patterns. Utilization of the theatre staff and time during the night
      has been improved.

PMID- 9560501
TI  - Variants of papillary carcinoma of the thyroid: experience at Asir Central
      Hospital.
AB  - Papillary carcinoma of the thyroid is now further subclassifiable into its
      different variants. We report incidence, clinical behaviour and outcome of rare
      variants of papillary thyroid cancers at Asir Central Hospital, Saudi Arabia.
      These variants differ from each other not only on a morphometric basis, but also
      in clinical behaviour. Accordingly, we report our experience of different
      variants in a series of 35 papillary carcinomas. These cases were received in the
      surgical pathology laboratory of Asir Central Hospital from January 1987 to
      December 1994. We have reviewed clinical charts, microscopic slides and
      pathological reports of these carcinomas. The following results have been
      obtained: 20 cases were classical (usual) papillary thyroid carcinomas: seven
      were follicular variants; three were tall cell/ columnar variants; two were
      oxyphilic variants; and one was a diffuse sclerosing variant. There were two de
      differentiated papillary carcinomas (anaplastic carcinomas with foci of well
      differentiated papillary carcinomas). These variants were also correlated with
      clinical parameters such as age, sex and nationality of the patients,
      aggressiveness of the tumours, types of surgery required, and follow-up when
      available.

PMID- 9560502
TI  - Effect of mangan-desferrioxamin in the prevention of peritoneal adhesions.
AB  - An experimental study was carried out using mangan-desferrioxamin chelate, an
      effective iron-chelating and free oxygen radical scavenging agent, to prevent
      post-operative peritoneal adhesions in 40 Wistar albino rats. The density of
      adhesions was evaluated and group scores obtained. The means score (2.5 +/- 0.87)
      for the group of rats treated with mangan-desferrioxamin was significantly
      different (P < 0.001) (95% confidence interval 0.6 to 1.6) from that of the
      control group(mean score 3.9 +/- 0.3). This favourable effect of mangan
      desferrioxamin in the prevention of post-operative adhesions should encourage
      further research to determine the mechanisms of action.

PMID- 9560503
TI  - Combined fascia and mesh closure of large incisional hernias.
AB  - Large incisional hernias of the abdominal wall represent substantial defects of
      supportive tissues. The repair of these requires the mobilization of fascia or
      the use of a prosthetic mesh. A method for closing large midline incisional
      hernias using both the fascia and a mesh was described in 1979. This repair was
      used for six midline hernias and four large incisional hernias in the right
      subcostal region. No wound complications and no recurrences (median follow-up 1
      year 5 months) were seen. The combined fascia and mesh repair can be successfully
      used for large incisional hernias of the anterior abdominal wall in areas other
      than the midline.

PMID- 9560504
TI  - Stapler failure in pharyngeal diverticulectomy: a suggested modification in
      surgical technique.
AB  - The use of a mechanical stapling device during excision of a pharyngeal pouch is
      now becoming more common, and has many advantages including less contamination of
      the wound by pharyngeal contents and a shorter operating time. The manufacturers
      recommend dividing the neck of the pouch flush with the stapler before removing
      the stapler. We report a case where the stapler failed, leaving a larger defect
      in the pharyngeal wall necessitating a hand sutured closure. We recommend a
      change in practice: an artery forcep is applied across the pouch distal to the
      stapler, the stapler is then removed and the staple line inspected before
      dividing the pouch.

PMID- 9560505
TI  - Obturator hernia: a new technique for repair.
AB  - An obturator hernia is exceedingly rare and the diagnosis is usually made at
      laparotomy for small bowel obstruction. Several methods of dealing with the
      hernial defect have been described. Two cases of obturator hernias in
      nonagenarians are reported and a new, simple and effective method of repairing
      the hernia by suturing a polypropylene (Prolene) mesh to Cooper's ligament is
      proposed.

PMID- 9560506
TI  - Tarsal tunnel syndrome: a study of the clinical and neurophysiological results of
      decompression.
AB  - The neurophysiological and clinical outcomes of surgical decompression of 22
      cases of tarsal tunnel syndrome are analysed. Recent work by Pfeiffer &
      Cracchiolo has suggested a successful outcome in only 44% of cases. We have
      reviewed the outcome of surgery both clinically and with the use of nerve
      conduction studies. Pre- and post-operative motor conduction delays in the
      plantar nerves are compared with clinical results found both in the clinic and
      later by a postal questionnaire. Despite careful clinical and neurophysiological
      assessment prior to a full surgical release, only 42% of patients had a
      satisfactory outcome. A larger reduction in plantar nerve conduction delay post
      operatively corresponded well to an improvement in symptoms. However, we were
      unable to predict which cases would respond to decompression using clinical or
      electrophysiological methods. We question the use of nerve conduction studies in
      the diagnosis of tarsal tunnel syndrome, and also the role of surgery in the
      management of this condition.

PMID- 9560507
TI  - Further uses of polymethylmethacrylate in orthopaedic surgery.
AB  - For over 30 years polymethylmethacrylate (PMMA) has been used in orthopaedic
      surgery to fix prosthetic components. Two additional uses, relying on the
      moulding properties previously utilized in dentistry, are described here: the use
      of PMMA as a bone graft template and as a femoral window plug in total hip
      replacement.

PMID- 9560508
TI  - Quadriceps pull test: an outcome predictor for lateral retinacular release in
      recurrent patellar dislocation.
AB  - Recurrent dislocation of the patella is a disorder with a complex aetiology.
      Several surgical procedures have been recommended for its correction, but there
      are few clinical or radiological guidelines to facilitate the selection of a
      particular procedure. The results of treating a series of 29 knees are presented
      with a follow-up of at least 2 years. A significant correlation has been found
      between the horizontal movement of the centre of the patella on quadriceps
      contraction (quadriceps pull test) and surgical outcome when lateral release
      alone is selected for the correction of recurrent patellar dislocation.

PMID- 9560509
TI  - Does early wound infection after elective orthopaedic surgery lead on to chronic
      sepsis?
AB  - Infection is an uncommon, but occasionally devastating, complication of
      orthopaedic surgery. The definition of post-operative infection remains
      problematic. A high rate of early post-operative sepsis has previously been
      reported using a clinical definition of wound infection as recommended by the
      Surgical Infection Study Group. The purposes of this study is to determine the
      rate of ongoing wound problems and deep sepsis 1 year after these early wound
      infections. Of 1131 consecutive orthopaedic procedures, there were 70 wound
      infections occurring within 30 days of surgery. Adequate follow-up data were
      obtained in 67 (97%) of the 69 patients alive at 1 year. Of these 67, three had
      definite evidence and two possible evidence of ongoing wound problems and/or deep
      sepsis. It is concluded that early post-operative wound infection as defined by
      the Surgical Infection Study Group is a poor predictor (4-10%) of ongoing wound
      problems and deep sepsis at 1 year. All of the confirmed cases of late sepsis
      were found to be associated with revision arthroplasty and/or pin tract sepsis.

PMID- 9560510
TI  - Profile of the first four years of the Regional Burn Unit based at St. John's
      Hospital, West Lothian (1992-1996).
AB  - In March 1992, the Regional Adult Burn Unit for the South East of Scotland in
      Bangour was transferred to the new District General Hospital in West Lothian.
      With the change in site and with changes in NHS policies and staff, it was
      expected that some difficulties would occur. An analysis of the initial situation
      was considered to be educational as well as of practical value. Parameters of
      mortality and infection were looked at in particular. The number of admissions of
      patients with burns (and notably those of 15% total body surface area or more)
      appears to be reducing annually; the mortality of 4.7% is comparable with
      Bangour, but the 42% mortality of patients with burns of 15% or more of the total
      body surface area is a cause for concern. Although the most common infectious
      organism in the Burn Unit remains Staphylococcus aureus, the advent of MRSA is
      worrying. The new unit has been closed twice because of bacterial infection. It
      is concluded that it is essential that patients with burns are managed in a
      separate Burn Unit within the District General Hospital and not amalgamated with
      other areas such as Intensive Care.

PMID- 9560511
TI  - A preliminary report: the changes in the neuropeptide containing epidermal
      innervation in response to inflammatory reactions elicited in human breast skin.
AB  - A pilot study was performed to demonstrate the involvement of the epidermal
      innervation in cutaneous neurogenic inflammation following injury or skin
      incision. Scratching human skin is known to evoke an inflammatory reaction
      dependent in part on sensory nerves (neurogenic inflammation) in the dermis.
      Human breast skin from four patients was scratched using a blunt metal ruler to
      elicit an inflammatory reaction. Samples of skin along the scratch line were then
      removed before and up to 5 min after scratching. Tissue samples were then stained
      using immunocytochemical techniques for the neuropeptides PGP 9.5, SP, CGRP and
      VIP. Quantitative assessment using image analysis demonstrated a marked variation
      between patients in the levels of epidermal PGP 9.5 innervation prior to
      scratching of the skin. In addition both increases and decreases in the epidermal
      innervation of PGP 9.5 were observed in different patients immediately after
      scratching. It is considered that epidermal innervation may have an important
      role in the inflammatory reaction to trauma and surgical operations and that a
      more extensive study is merited.

PMID- 9560512
TI  - Spontaneous retroperitoneal haemorrhage associated with renal disease.
AB  - Spontaneous retroperitoneal haemorrhage is an uncommon entity. It is even rarer
      when the underlying cause is associated with renal disease. In most cases the non
      traumatic rupture of a kidney requires an emergency surgical intervention as the
      underlying disease only becomes clear intra-operatively. Most patients with a
      spontaneous kidney rupture have a renal tumour. Of these renal tumours,
      angiomyolipomas show a particular tendency to rupture. The cases are reported of
      five patients who presented with an acute onset of spontaneous retroperitoneal
      haemorrhage from different kidney disorders. The importance of considering the
      possibility of spontaneous kidney rupture in the evaluation of patients
      presenting with spontaneous retroperitoneal haemorrhage is stressed.

PMID- 9560513
TI  - Conservative management of splenic rupture in a haemophiliac adult.
AB  - The recognition of the grave risk of overwhelming sepsis in splenectomized
      individuals has led to the search for alternatives to splenectomy. Conservative
      management, first tried successfully in children and later extended to adult
      patients, has become the accepted form of treatment and has also been tried with
      success in haemophiliac children. The case presented here is important because
      this is the first report of a successful outcome of non-operative treatment of a
      ruptured spleen in a haemophiliac adult.

PMID- 9560514
TI  - A lump in the groin: an unusual presentation of loose hip prosthesis.
AB  - We describe the loose hip prosthesis presenting as a mass in the groin, with a
      collection of titanium and polyethylene debris within the ileopsoas bursa.
      Titanium tissue staining has been noted, at the time of revision of titanium
      prostheses, but frank ileopsoas bursitis presenting as a groin mass, after hip
      replacement has not previously been described.

PMID- 9560515
TI  - Selective arterial embolization in the treatment of arterial priapism.
AB  - Arterial or 'high-flow' priapism is a rare complication of penile or perineal
      trauma. The case is reported of a patient with a more than 2-week history of
      priapism who was successfully treated by selective arterial embolization, with
      maintenance of potency.

PMID- 9560516
TI  - Non-iatrogenic perforation of the stomach by a chest tube in a patient with
      traumatic diaphragmatic hernia.
AB  - A 40-year-old Libyan male was admitted to the intensive therapy unit of Zliten
      Central Hospital, Libya after a road traffic accident in which he had been the
      driver. On physical examination he was irritable, dyspnoeic, cyanotic, had
      contusions and abrasions on his chest and abdomen (mainly on the left side), a
      lacerated wound on the forehead, a large haematoma over the left thigh and
      tenderness over the left side of the chest and abdomen.

PMID- 9560517
TI  - Endoscopic sigmoidopexy: a safer way to treat sigmoid volvulus?
AB  - Sigmoid volvulus may be treated by sigmoidoscopic reduction and elective
      sigmoidopexy or resection at a later stage, provided there is no evidence of
      peritonitis, perforation or rectal bleeding. However, operative treatment,
      whether urgent or elective, is associated with a relatively high morbidity and
      mortality. An endoscopic technique of sigmoidopexy is reported which is
      relatively quick and straightforward to perform, and is likely to have a lower
      rate of morbidity and mortality than conventional techniques for the treatment of
      sigmoid volvulus.

PMID- 9560518
TI  - Pancreatic tuberculosis: case reports and review of the literature.
AB  - Tuberculosis affecting the pancreas is rare. Its occurrence may pose a diagnostic
      problem in differentiating it from carcinoma of the pancreas. Two cases of
      tuberculosis affecting the pancreas are reported, illustrating the value of fine
      needle aspiration in such a situation. The response of the disease to
      antituberculous drugs was slow, but sure.

PMID- 9560519
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9560520
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9560521
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9560522
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9560523
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9560525
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9560524
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9560526
TI  - The response of liver macrophages to inflammatory stimulation.
AB  - The gut is the major source of inflammatory agents that affect the liver. Of
      these compounds, the endotoxins are the most frequent and best studied intruders.
      The resident macrophages of the liver, the Kupffer cells, are among the first to
      respond to this complex. Following contact with the cluster of differentiation
      (CD) 14 protein, the complex triggers a signal cascade involving the nuclear
      factor kappa B. This factor enhances the expression of inflammation-related
      genes, e.g. those encoding cytokines. Tumor necrosis factor-alpha is responsible
      for nearly all of the effects ascribed to endotoxins (lipopolysaccharides).
      Interleukin (IL)-6, also a product of lipopolysaccharide-activated Kupffer cells,
      may be instrumental in eliciting the acute-phase response of hepatocytes, while
      transforming growth factor-beta promotes conversion of quiescent hepatic stellate
      cells into a collagen-producing myofibroblast-like form. A different signal
      pathway triggered by bound endotoxin involves a mitogen-activated protein kinase
      and leads to the activation of phospholipase A2 and the synthesis of the
      eicosanoids. Endotoxin also induces a nitric oxide synthase in Kupffer cells.
      This inorganic mediator may participate in the relaxation of the hepatic
      sinusoid, but may also, together with macrophage-derived superoxide, produce
      strong oxidants. Tumor necrosis factor-alpha and nitric oxide play a significant
      role during liver regeneration after partial hepatectomy. Of the various effects
      of eicosanoids, their regulatory role in cytokine production by Kupffer cells may
      be the most important. The regulation of Kupffer cell functions by cell volume
      change has very recently become apparent.

PMID- 9560527
TI  - Mucin glycoproteins in colonic neoplasia.
AB  - Mucins are high molecular weight glycoproteins which are heavily glycosylated
      with many carbohydrate side chains. In epithelial cancers such as colorectal
      cancer, both qualitative and quantitative alterations in carbohydrate and
      polypeptide moieties of mucin glycoproteins occur. These changes in mucin
      glycoproteins are one of the most common phenotypic markers of colorectal
      carcinogenesis and may play an important pathobiological role. The expression of
      some of the sialylated carbohydrate antigens appears to correlate with a poor
      prognosis and increased metastatic potential in colorectal cancer. The increased
      exposure of peptide epitopes of mucin glycoproteins in colorectal cancer appears
      to be due to either abnormal glycosylation and/or altered levels of mucin gene
      transcription. In addition, dysregulation of tissue specific mucin genes occurs
      in colorectal cancers. This information is currently being exploited for further
      elucidation of the molecular mechanisms involved in carcinogenesis, tumor
      progression and metastasis, and the development of novel methods of colorectal
      cancer diagnosis and therapy.

PMID- 9560528
TI  - Evaluation of systemic inflammatory response syndrome criteria as a predictor of
      mortality in emergency patients transported by ambulance.
AB  - Based on the concept of the systemic inflammatory response syndrome (SIRS), a one
      year retrospective study was carried out to examine SIRS criteria as a simple and
      rapid predictor of outcome for emergency patients. Among a total of 2,180
      patients transported to the emergency room by ambulance, 318 (14.8%) had primary
      SIRS and 389 (17.8%) met SIRS criteria at some point during the entire treatment
      period. The admission rate for primary SIRS increased sequentially as more SIRS
      criteria were met, rising from 15.4% in non-SIRS to 100% when all four criteria
      were met. The mortality of primary SIRS also increased sequentially as more SIRS
      criteria were met, rising from 1.4% in non-SIRS to 35.3% when all four criteria
      were met. Furthermore, heart rate, C-reactive protein and platelet count were
      considered to be potentially useful new criteria for a group of SIRS patients
      with a high risk of mortality (high-risk SIRS), based on a comparison of
      variables between SIRS patients who died and SIRS patients who survived. The
      mortality associated with primary SIRS increased sequentially as more high-risk
      SIRS criteria were met, rising from 7.6% when none were met to 50.0% when two
      criteria were met. Considering the high specificity of primary SIRS for admission
      (89.5%) and mortality (86.8%), SIRS criteria have clinical and prognostic
      importance in the management of emergency patients. Given the high mortality
      (29.9%), the new high-risk SIRS criteria may also be useful as entry criteria for
      clinical trials of innovative therapies for patients with SIRS.

PMID- 9560529
TI  - Vector autoregressive modeling analysis of frequently sampled oral glucose
      tolerance test results. 1. A new method for quantifying insulin resistance and
      secretion.
AB  - To elucidate abnormalities in the feedback relationships between plasma glucose
      and plasma insulin levels in diabetic patients, we have introduced the vector
      autoregressive modeling method as a new for tool feedback analysis. This
      technique was applied to plasma glucose and insulin level data from a series of
      977 frequently-sampled oral glucose tolerance tests (FS-OGTT). Neither special
      instruments nor medications were used in FS-OGTT. We were able to predict the
      degree of the plasma glucose response occurring after an impulse-like increase in
      plasma insulin at 1 mU/mL, as well as the plasma insulin response triggered by an
      impulse-like increase in plasma glucose at 1 mg/dL, in the form of "impulse
      response curves". The predicted impulse response curve of glucose to insulin
      gradually changed from negative to positive with incremental changes in the
      fasting plasma glucose level, reflecting increased insulin resistance.
      Furthermore, the response of insulin to glucose decreased in a stepwise fashion
      with the incremental changes in the fasting plasma glucose level. Our findings
      confirm the usefulness of impulse response curves as clinical indicators. In
      addition, analytical data point to a possible contribution of excessive hepatic
      glucose production to the pathogenesis of the insulin resistance in non-insulin
      dependent diabetes mellitus.

PMID- 9560530
TI  - Fluorometric measurement of intracellular pH in vivo in feline cerebral cortex
      during ischemia and reperfusion.
AB  - Intracellular acidosis has been considered to play an pivotal role in the
      progression of neuronal damage after cerebral ischemia. However, continuous
      measurement of the intracellular potential of hydrogen (pH) has not been done
      during and after ischemia. We measured temporal changes in intracellular pH in
      the feline cerebral cortex in vivo during and after ischemia using a novel
      fluorescent pH probe, 2',7'-biscarboxyethyl carboxyfluorescein (BCECF). A closed
      cranial window was installed in the left temporal skull. BCECF acetoxymethyl
      ester was superfused over the cortex, hydrolyzed and trapped in cortical cells.
      Intracellular pH was measured utilizing excitation light at 507 nm and
      fluorescent light at 550.5 nm. Focal cerebral ischemia for 60 minutes was induced
      by means of middle cerebral artery occlusion. Intracellular pH in the severely
      ischemic group became significantly acidic (p < 0.01) during ischemia and the
      acidosis persisted for at least 30 minutes after recirculation. The pH change was
      not significant in the mildly ischemic group. The severity of ischemia was
      determined based on the mean transit time, which was calculated from the
      hemodilution curve obtained by bolus injection of saline. The extent of ischemia
      was further confirmed pathologically (p < 0.01). The above results suggest that
      intracellular acidosis resulting from severe ischemia persists even after
      recirculation.

PMID- 9560531
TI  - Molecular approaches to the treatment of Fanconi anemia: recent advances.
AB  - Fanconi anemia (FA) is an autosomal recessive disorder that leads to aplastic
      anemia. Cells from FA patients are abnormally sensitive to DNA cross-linking
      agents such as mitomycin C. FA consists of at least five subgroups (FA-A through
      E). The genes defective in the FA-C and FA-A groups have recently been cloned.
      Transfection of the normal FA gene into mutant cells corrects the
      hypersensitivity to DNA cross-linking agents and improves cell viability in
      vitro. The function of the FA gene products is still unclear, however. For
      patients lacking a compatible bone marrow transplantation donor, an experimental
      trial of gene therapy for group C FA is ongoing at the National Institutes of
      Health.

PMID- 9560532
TI  - A case of rapidly progressing small cell lung cancer incidentally found during
      the course of renal failure.
AB  - A 65-year-old man with rapidly progressing small cell lung cancer found in the
      course of renal failure is reported. The patient had a medical history of
      hypertension, diabetes mellitus, and cardiovascular disease. Hemodialysis was
      introduced following renal failure, but pneumonia resulted in a transient
      exacerbation and his complaint of general fatigue did not improve. Examination
      for the fatigue revealed no apparent abnormalities. Three months later, he died
      of small cell lung cancer.

PMID- 9560535
TI  - [Assessment of the practicability of coronary risk index as a screening method
      for ischemic heart disease in preoperative evaluation].
AB  - Coronary risk index (CRI) is our newly developed screening method for ischemic
      heart disease in preoperative evaluation. In this study, we assessed the
      practicability of CRI examining coronary angiograms (CAG) obtained in 106
      patients scheduled for operations. CAG was rated with CAG score, then CRI and CAG
      score were statistically analyzed. These two parameters showed a significant
      positive relationship; the higher CRI, the higher CAG score (P < 0.0001). When
      the patients were divided into five groups by their CRI (0-9, 10-14, 15-19, 20
      24, and more than 25), the group with higher CRI contained significantly more
      patients with severe multivessel coronary lesion (P < 0.0001). Similar results
      were obtained even in the patient with minimal change in ECG or exercise ECG, or
      those with minimal chest symptoms (P < 0.001). These results suggests that CRI
      works effectively as a screening method for ischemic heart disease regardless of
      abnormalities in ECG or the chest symptoms. More cautious perioperative
      management should be carried out in patients with higher CRI.

PMID- 9560534
TI  - [Analysis of postoperative shivering following the deliberate mild hypothermia
      during neurosurgery].
AB  - We induced deliberate mild hypothermia in 96 patients who underwent intracranial
      operations using a water blanket and a convective device blanket. The lowest
      temperature measured at the tympanic membrane during mild hypothermia was
      adjusted to 34.5 degrees C. The patients were divided into two groups in respect
      to the occurrence of postoperative shivering, and the relationship between the
      perioperative parameters and the occurrence of postoperative shivering was
      evaluated. Shivering was observed postoperatively in 29 to 96 patients (30.2%).
      In the group with shivering (SV), age was significantly lower and body weight and
      body surface area were significantly larger than the group without shivering
      (NSV). Urinary output was significantly larger in SV than in NSV. Tympanic
      membrane, nasopharyngeal, and rectal temperatures at the end of surgery and
      nasopharyngeal, rectal, and peripheral temperatures just after the extubation
      were significantly lower in SV than in NSV. These results suggest that sufficient
      rewarming of both the core and peripheral temperatures is important to prevent
      the postoperative shivering following the mild hypothermic therapy in
      neurosurgical patients, especially in young patients.

PMID- 9560537
TI  - [Effect of temperature on Ca induced Ca release (CICR) rate].
AB  - The aim of this study is to assess the effect of temperature on CICR rate. The
      extensor digitorum longus muscles of male Hartley guinea pigs of about 450 g,
      were prepared for this study. According to Endo's method, CICR rates were
      measured using chemically skinned fibers. Two plates were prepared: one at 20
      degrees C and the other at 30, 35, 37, 40 degrees C controlled by circulating
      water at an appropriate temperature placed underneath each plate. The whole
      procedure was carried out at 20 degrees C except the step of CICR using a plate
      at a given temperature. An increase in temperature (20 to 40 degrees C)
      accelerated CICR rate in a logarithmic manner. These experimental findings
      suggest that cooling of the patient's body is important not only to control
      metabolism but also to reduce an accelerated CICR rate.

PMID- 9560536
TI  - [Pharmacokinetics of propofol and ketamine during and after total intravenous
      anesthesia with propofol, fentanyl and ketamine for pediatric patients].
AB  - Pharmacokinetics of propofol and ketamine during propofol-fentanyl-ketamine (PFK)
      anesthesia for pediatric surgery was studied. Plasma levels of propofol (Pp) were
      maintained approximately at 2.5 micrograms.ml-1 during surgery. Fifteen minutes
      after the cessation of propofol infusion, Pp decreased to 1.5 micrograms.ml-1.
      Plasma levels of ketamine (Pk) were maintained at 150-200 ng.ml-1 during the
      surgery. After the cessation of ketamine infusion, Pk decreased as quickly as Pp.
      Pk values at 15 minutes and 120 minutes after the cessation of the infusion were
      93 ng.ml-1, 24 ng.ml-1, respectively. On the other hand, plasma norketamine (Pn)
      levels increased gradually during surgery and stayed at 100-150 ng.ml-1 after the
      end of ketamine infusion to play an important role in post-operative sedation and
      pain relief. In conclusion, pharmacokinetics of propofol and ketamine in
      pediatric patients was similar to that in adult patients. PFK anesthesia can be
      used safely for pediatric as well as for adult patients.

PMID- 9560538
TI  - [A comparison of the incidence of postoperative nausea and vomiting after
      propofol-fentanyl anesthesia and that after nitrous oxide-isoflurane anesthesia].
AB  - We compared the incidence of postoperative nausea and vomiting after total
      intravenous propofol-fentanyl anesthesia (TIVA group) and that after thiamylal
      nitrous oxide-isoflurane anesthesia (GOI group) in 60 ASA physical I and II
      patients for elective abdominal simple total hysterectomy. When the patients
      returned to the ward, the incidence of nausea was lower in TIVA group than in GOI
      group (P < 0.05), but no difference was found in the incidence of vomiting
      between the two groups. There were no differences in the incidence of nausea and
      vomiting 6 hours after the operation and on the next morning between the two
      groups. Postoperative pain scores were similar between the two groups, while
      total postoperative evaluation scores (nausea, vomiting, pain, fever, and sleep
      disturbance) were lower in TIVA group (P < 0.05). We conclude that TIVA with
      propofol-fentanyl reduced the incidence of nausea and improved total evaluation
      scores in the immediate postoperative period.

PMID- 9560539
TI  - [A study of post-operative delirium in elderly patients].
AB  - We investigated the post-operative delirium in elderly patients of over 65 years
      of age. This investigation consisted of two studies, a prospective study and a
      retrospective study. In the prospective study, we evaluated the incidence of post
      operative delirium and the incidence of post-operative delirium was estimated pre
      operatively using State-Trait Anxiety Inventory (STAI) and Mini Mental State
      Examination (MMSE) in 24 patients scheduled for elective surgery under general
      anesthesia in the period from Nov. 1995 to Oct. 1996. In the retrospective study,
      we selected patients with post-operative delirium from 1600 patients who had
      undergone scheduled and emergency operation under general anesthesia in the same
      period as in the prospective study and analyzed the incidence of post-operative
      delirium and background of these patients. Twenty four patients in the
      prospective study were excluded from the retrospective study. In the prospective
      study, although post-operative delirium was observed in 2 cases (8.3%), no
      specific changes were observed in anxiety state and the ability of recognition.
      In the retrospective study, post-operative delirium was observed in 22 cases
      (1.37%). In these patients, several factors such as blood transfusion, emergency
      operation, dehydration, thrombosis of the superior mesenteric artery, history of
      ischemic heart disease, brain infarction and atrial fibrillation were thought to
      be major risk factors triggering post-operative delirium. In this study we could
      not conclude that STAI or MMSE are useful to estimate the incidence of post
      operative delirium preoperatively. However, our result suggests that we should be
      careful about the incidence of post-operative delirium in elderly patients with
      pre-operative risk factors as mentioned above.

PMID- 9560540
TI  - [A case report: inhaled nitric oxide improves respiratory function in an infant
      with pulmonary hypertension].
AB  - Nitric oxide (NO) was administered to an infant in a near fatal crisis of
      pulmonary hypertension after total correction of double outlet right ventricle.
      Inhaled NO of 4 parts per million reduced pulmonary arterial pressure (PAP) and
      increased tidal volume during pressure limit ventilation. Both respiratory system
      compliance and resistance were improved with NO inhalation. There was a
      significant negative correlation between mean PAP and respiratory system
      compliance. We speculated that a reduction in PAP with NO inhalation resulted in
      the improvement of respiratory function. He was successfully weaned from
      mechanical ventilation.

PMID- 9560541
TI  - [Anesthetic management of parturients with intracranial hemorrhage accompanied by
      seizure].
AB  - Two preeclamptic parturients, who presented with generalized seizure, underwent
      emergency cesarean section without confirmed diagnosis. They developed focal
      neurological signs postoperatively, and were subsequently diagnosed as
      subarachnoid hemorrhage due to rupture of an intracranial aneurysm and possibly
      of arteriovenous malformation. Diagnosis should be made at the earliest possible
      time for the optimal anesthetic as well as postoperative management of the
      mother.

PMID- 9560542
TI  - [Anesthetic management for microlaryngeal surgery with high frequency jet
      ventilation and intravenous application of pentazocine and propofol].
AB  - Microlaryngeal surgery was performed with total intravenous anesthesia using
      pentazocine and propofol in 20 patients. The patients were paralyzed by
      suxamethonium infusion and ventilated by high frequency jet ventilation via the
      laryngoscope. In place of the opioid analgesics commonly used in TIVA for
      microlaryngeal surgery, pentazocine was given. All but one of the patients
      received pentazocine 15 m.g. intramuscularly as a premedication and then another
      15 m.g. intravenously for induction of anesthesia. Average time of surgeries was
      33.6 minutes. Average doses of pentazocine and suxamethonium given during
      surgeries were 369 m.g. and 286 m.g., respectively. This technique allowed stable
      anesthesia to be achieved with rapid postoperative recovery, without serious
      complications like intraoperative return of awareness.

PMID- 9560543
TI  - [Clinical indication of propofol for pediatric patients--pharmacokinetics of
      propofol and ketamine during and after total intravenous anesthesia with
      propofol, fentanyl and ketamine (PFK) in a neonate].
AB  - A 60-day-old neonate boy received hepatic portojejunostomy for biliary atresia
      under PFK. Pharmacokinetics of propofol and ketamine during and after PFK was
      also studied. Plasma levels of propofol (Cp) and ketamine (Ck) were maintained at
      2 to 3 micrograms ml-1 and at 200 to 300 ng ml-1 during surgery, respectively.
      Both Cp and Ck decreased quickly after the end of infusions. From the
      pharmacokinetic point of view, PFK may be safely applied even for neonates.

PMID- 9560544
TI  - [The effect of scalp infiltration with bupivacaine on blood coagulability and
      fibrinolysis in neurovascular surgery].
AB  - We investigated the effect of scalp infiltration with bupivacaine on blood
      coagulability and fibrinolysis in neurovascular surgery. Patients were randomly
      divided into two groups: scalp infiltration group (who received scalp
      infiltration with 0.5% bupivacaine prior to surgical incision, n = 7) and control
      group (n = 6). The blood coagulability and fibrinolysis were measured before and
      after surgical incision using a thromboelastogram (Thromboelastograph C-3000,
      Haemoscope). In the control group, the reaction and coagulation times were
      significantly shortened (30% and 23%, respectively, P < 0.05) and the maximum
      amplitude, which reflects coagulability, increased significantly (21%, P < 0.01)
      compared to each presurgical value. The scalp infiltration prior to the surgical
      incision prevented these reactions (P < 0.05). The fibrinolytic rate did not
      change in either group. We conclude that scalp infiltration prior to surgical
      incision is beneficial for attenuating an increase in blood coagulability, which
      could induce perioperative complications due to associated systemic diseases
      (i.e. hypertension, diabetes, ischemic heart disease, etc.).

PMID- 9560545
TI  - [Activation of bradykinin formation cascade on receiving autologous blood
      transfusion through a white cell-reduction filter in a patient treated with an
      ACE inhibitor].
AB  - We have experienced a case of anaphylactoid reaction on receiving autologous
      blood transfusion through a WBC filter for packed red blood cell (PRBC). The
      patient was a 71-year-old man with a history of hypertension treated with oral
      antihypertensive drug; enalapril, an angiotensin converting enzyme (ACE)
      inhibitor, who received anesthesia for Y-graft replacement. Autologous blood was
      obtained after the induction of general anesthesia in the operating room. Upon
      starting to return the stored blood with an unintentional use of a WBC filter,
      arterial blood pressure (ABP) fell within the first minute of the transfusion. We
      obtained three blood samples; pre-filtered blood (PRE), postfiltered blood (POST)
      and arterial blood (CIRC) after the event, and analyzed concentrations of
      bradykinin (BK), high molecular weight kininogen (HMWK) and high molecular weight
      kininogen-light chain (HMWK-LC). BK was higher in POST than in PRE. HMWK was
      lower in POST than in PRE, while HMWK-LC was higher in POST than in PRE. HMWK in
      CIRC was lower than in PRE, and HMWK-LC was higher in CIRC than in PRE. HMWK and
      HMWK-LC changes after the event suggest that BK formation cascade in the patient
      was activated on receiving the transfusion. ACE inhibitors were reported to
      augment such activation. The WBC filter has the negatively charged surface on
      filteration material and may activate the cascade. While WBC filters can avoid
      transfusion related reactions, hemodynamic responses should be watched closely in
      patients treated with ACE inhibitors.

PMID- 9560546
TI  - [Anaphylactoid shock caused by chlorhexidine gluconate].
AB  - We report two cases of anaphylactoid shock caused by chlorhexidine gluconate.
      Both patients had skin flare, severe hypotension and increased airway pressure
      during cannulation of an antibacterial IVH catheter containing chlorhexidine
      gluconate after skin sterilization with chlorhexidine gluconate. In case 1, we
      did not identify the mechanism and causative drugs. In case 2, an intradermal
      test to chlorhexidine gluconate was positive 2 months later. Then we confirmed
      that the anaphylactoid shock was caused by chlorhexidine gluconate. We should
      bear in mind the risk of anaphylactoid shock when we use chlorhexidine gluconate
      or the IVH catheter containing the bactericide.

PMID- 9560548
TI  - [A successful perioperative anticoagulation therapy and monitoring of a patient
      with hereditary plasminogen abnormality undergoing aortic valve replacement].
AB  - During perioperative period, plasminogen abnormality can result in unusual or
      unexplained clotting that occurs spontaneously or after minor trauma. However,
      there has been no report on perioperative anticoagulation therapy and monitoring
      in patients with hereditary plasminogen abnormality undergoing cardiac surgery.
      We performed a successful perioperative anticoagulation therapy and monitoring of
      a patient with hereditary plasminogen abnormality undergoing cardiac surgery. A
      48-year-old male patient with severe aortic valve stenosis, who had had no
      episode of thrombosis, was scheduled for aortic valve replacement Preoperative
      laboratory screenings detected his abnormal plasminogen activity (7.6% normal),
      and he was diagnosed as hereditary plasminogen abnormality. Anesthetic course was
      uneventful until the initiation of cardiopulmonary bypass (CPB). During CPB,
      heparin level was monitored every 30 minutes by Hepcon/HMS (Medtronic Hemotec,
      Parker, CO). No thrombus was observed in the CPB circuit. Plasminogen activity,
      fibrin degradation products (FDP) and D-dimer were not elevated during
      perioperative period. Protamine dosage was determined by protamine titration
      method, and protamine was administrated after the termination of CPB. No major
      bleeding was observed after protamine administration. When the patient was
      admitted to ICU, anticoagulation therapy was started immediately. During
      perioperative period, no episode suggesting thrombosis was observed. In
      conclusion, we consider that this successful anticoagulation therapy and
      monitoring during CPB has been achieved by use of Hepcon/HMS.

PMID- 9560547
TI  - [Regional cerebral oxygen saturation as a monitor of cerebral oxygenation and
      perfusion during deep hypothermic circulatory arrest and selective cerebral
      perfusion].
AB  - In order to evaluate cerebral oxygenation and perfusion during deep hypothermic
      circulatory arrest (DHCA) and selective cerebral perfusion (SCP), continuous
      measurement of regional cerebral oxygen saturation (rSO2) by near-infrared
      spectroscopy (NIRS) was performed. Two patients undergoing aortic arch surgery
      performed under DHCA and SCP were studied. 1) Circulatory arrest produced a
      continuous decrease in rSO2. Introduction of SCP increased rSO2 to even above the
      pre-circulatory arrest level (reperfusion hyperoxia). 2) During SCP, changes in
      rSO2 correlated well with the naso-pharyngeal temperature, SCP flow rate, and
      level of carbon-dioxide insufflation to SCP. 3) These changes in rSO2 paralleled
      with those of jugular venous hemoglobin saturation (SjO2) measured
      simultaneously, although SjO2 frequently exhibited artifacts. We conclude that
      rSO2 measurement may be a non-invasive and continuous measure in the evaluation
      of cerebral oxygenation and perfusion during DHCA and SCP.

PMID- 9560549
TI  - [Two elderly patients with thoracic herpetic pain and post herpetic neuralgia
      treated with continuous thoracic sympathetic ganglion block through a placed
      catheter].
AB  - Epidural block is very useful in the treatment of herpetic pain and post herpetic
      neuralgia. However, in the elderly patients with cardiac disease or diabetes
      mellitus, severe cardiovascular changes may occur by epidural block. Epidural
      block caused severe hypotension in two elderly patients with herpetic pain and
      post herpetic neuralgia who had diabetes mellitus or hypertension. Continuous
      thoracic sympathetic ganglion block with local anesthetics through a placed
      catheter reduced their pain and caused almost no changes in cardiovascular
      system.

PMID- 9560550
TI  - [Recurrent nerve palsy after endotracheal intubation].
AB  - We encountered left recurrent nerve palsy in four patients who had undergone
      surgery unrelated to the course of the vagus nerve or recurrent nerve, during
      which they had received endotracheal anesthesia. They were intubated without
      difficulty and underwent surgery without trouble, but postoperatively they all
      complained of hoarseness. We used a disposable ENTRASOFT endotracheal tube with
      high volume, low-pressure cuff in three patients and a disposable PORTEX
      endotracheal tube with low volume, standard cuff in one patient. In three
      patients recurrent nerve palsy healed completely within two months after the
      operation, and one patient was recovering from the palsy on the twentieth day
      after the operation. We believe that the most plausible explanation of recurrent
      nerve palsy is the excessive pressure from the inflated endotracheal tube cuff on
      the intralaryngeal course of the anterior branch of the recurrent nerve.
      Monitoring cuff pressure is most important to prevent recurrent nerve palsy after
      endotracheal intubation.

PMID- 9560551
TI  - [Anesthesia for a child with congenital sensory neuropathy with anhydrosis].
AB  - We gave anesthesia twice to a 4-year-old boy with congenital sensory neuropathy
      with anhydrosis. At the first surgery, anesthesia was induced with midazolam and
      maintained with nitrous oxide, oxygen and sevoflurane 0.5-0.8% under mask
      breathing. Surgery was performed without any trouble but the patient vomited
      postoperatively for three days. Next time, anesthesia was induced and maintained
      with propofol under mask. The patient often moved during surgery, and therefore,
      we changed from propofol to oxygen and sevoflurane 1.0-1.5% anesthesia. Nitrous
      oxide was not used. After the surgery, no vomiting occurred.

PMID- 9560552
TI  - [Cerebral oxygen saturation and hemoglobin index under separate brain perfusion].
AB  - We monitored bilateral cerebral oxygen saturation and hemoglobin index while the
      brain received separate perfusion for major vascular surgery. Before surgery,
      left cerebral oxygen saturation and hemoglobin index were within normal limits
      but right cerebral oxygen saturation and right hemoglobin index were low. At the
      end of surgery, right cerebral oxygen saturation was elevated and almost equal to
      left cerebral oxygen saturation, and right hemoglobin index was elevated too but
      slightly lower than left hemoglobin index. We found that oxygen delivery to the
      right cerebral hemisphere improved in comparison with presurgical period. No
      paralysis or any other neurological complications occurred postoperatively. We
      conclude that such monitoring is useful during and after anesthesia under
      separate brain perfusion.

PMID- 9560553
TI  - Opportunities and dangers in the changing health care system.

PMID- 9560554
TI  - Speculations on the etiology of malaria.

PMID- 9560555
TI  - A pediatric perspective on the RIte Care Program.

PMID- 9560556
TI  - RIte Care.

PMID- 9560557
TI  - Implementing a computer-based mammography education project in a managed care
      setting.

PMID- 9560558
TI  - Geriatric assessment in an HMO.

PMID- 9560559
TI  - The impact of managed care on chronic care agency providers.

PMID- 9560560
TI  - The emergence of Medicare managed care: Implications for the post-acute sector.

PMID- 9560561
TI  - Rhode Island Health Plan Program summary.

PMID- 9560562
TI  - Health care quality improvement in Rhode Island.

PMID- 9560563
TI  - Enrollment in HMOs in Rhode Island.

PMID- 9560564
TI  - The Diagnosis and management of osteoporosis: current considerations.

PMID- 9560565
TI  - Physician unions: The wave of the future?

PMID- 9560566
TI  - A philatelist's history of smallpox variolation.

PMID- 9560568
TI  - Biomimetics: the next great revolution in dentistry. Interview by Phillip Bonner.

PMID- 9560567
TI  - Using laser technology on hard tissue.

PMID- 9560569
TI  - Dental implants and coronal bone loss: an evaluation of 350 implants.

PMID- 9560570
TI  - Integrating implants into the GP practice: innovative technology and simplified
      techniques.

PMID- 9560571
TI  - Metal-free full-posterior coverage.

PMID- 9560572
TI  - Nightguard vital bleaching.

PMID- 9560573
TI  - Microscope revolution.

PMID- 9560574
TI  - Electrosurgery for crown and bridge.

PMID- 9560575
TI  - Intentional composite lip on subgingival Class V restorations.

PMID- 9560576
TI  - Understanding networks.

PMID- 9560577
TI  - Proposed bill would treat HIV as infectious disease.

PMID- 9560578
TI  - Direct composite technique for a smile makeover.

PMID- 9560579
TI  - A team approach to a brighter smile.

PMID- 9560580
TI  - Indirect composite veneers.

PMID- 9560582
TI  - Polyethylene fiber reinforcement for interim restorations and postendodontic
      rehabilitation.

PMID- 9560581
TI  - Class III composite restorations.

PMID- 9560583
TI  - A look at the past and future. Interview with Gordon Christensen, DDS, PhD.
      Interview by Phillip Bonner.

PMID- 9560584
TI  - Dentistry 2000: meeting the global challenge of change. Interview by Cheryl Farr.

PMID- 9560585
TI  - Periodontal microsurgery.

PMID- 9560586
TI  - Current concepts in periapical surgery.

PMID- 9560587
TI  - Scheduling the new patient exam and prophy.

PMID- 9560588
TI  - Eliminating opportunistic infection is essential for AIDS patients.

PMID- 9560589
TI  - Enhancing precision through magnification.

PMID- 9560590
TI  - Simplifying single anterior crown aesthetics.

PMID- 9560591
TI  - Using noncasting technology as an alternative to traditional C&B techniques.

PMID- 9560592
TI  - Reconstructive endodontics.

PMID- 9560593
TI  - Dental lasers: have recent advances renewed interest?. Interview by Dan Marino.

PMID- 9560594
TI  - Aesthetic screw access openings for abutment retained fixed prostheses: one-stage
      implants.

PMID- 9560595
TI  - Dental unit waterlines: is this one of dentistry's compelling problems?

PMID- 9560596
TI  - Strategies for treating the dental phobic.

PMID- 9560597
TI  - First looks for '98: a guide to the newest clinical techniques and technology.

PMID- 9560598
TI  - Equipping the general practice: evaluating new technologies. Interview by Phillip
      Bonner.

PMID- 9560599
TI  - Stroke, Alzheimer's patients may benefit from AIDS dementia drug.

PMID- 9560600
TI  - Teledental network: dental education in a new millennium.

PMID- 9560601
TI  - Combining a philosophy with a plan for success. Interview by Phillip Bonner.

PMID- 9560602
TI  - A glance at gingiva.

PMID- 9560603
TI  - Micro-endodontic nonsurgical retreatment: silver point removal.

PMID- 9560604
TI  - Obturation with preheated multiphase gutta percha.

PMID- 9560605
TI  - Effective use of mixed media to correct aesthetic deficiencies.

PMID- 9560606
TI  - Nerve injuries following procedures in general practice.

PMID- 9560608
TI  - Dysfunction of the human mastication system.

PMID- 9560607
TI  - Stabilizing dentures on a severely resorbed mandible.

PMID- 9560609
TI  - Reducing stress in the operatory.
AB  - Dentists can minimize the levels of physical and mental stress in dental offices
      by selecting suitable equipment and maintaining proper posture. The specific
      positions and allowable movements require a vigilant attitude on the part of
      dentists until these habits become established and are practiced routinely.

PMID- 9560610
TI  - What the general practice will look like in 2001.

PMID- 9560611
TI  - The top 10 technologies.

PMID- 9560612
TI  - Porcelain laminate veneers to restore worn lower teeth.

PMID- 9560613
TI  - New applications for new materials.

PMID- 9560614
TI  - Midface collapse: an overlooked disease.
AB  - Midface collapse is a disease caused by occlusal interferences leading to
      excessive tooth attrition and loss of vertical dimension. Although it can cause
      premature aging, it can be prevented or treated.

PMID- 9560615
TI  - Air abrasion: the new "drill-less" dentistry. Interview by Phillip Bonner.

PMID- 9560616
TI  - Dentin and pulp simulation in ceramic restorations.

PMID- 9560617
TI  - The design of the clasped removable partial denture.

PMID- 9560618
TI  - The files of greater taper: report from the trenches.

PMID- 9560619
TI  - Orthopedics, oral surgery, and orthodontia: the past is always with us.

PMID- 9560620
TI  - Sealing caries out ... or in?

PMID- 9560621
TI  - Increase efficiency and decrease stress.
AB  - We have covered the benefits of using three key communication systems, including
      the lighting (or digital) system, placing patient's charts in a holding area at
      the front desk, and the importance of using and discarding your telephone slip.
      The more a practice can systematically organize operations, the more quality time
      is left for patient communication and service.

PMID- 9560622
TI  - It's live and it's through the Internet.

PMID- 9560623
TI  - Alternative approach to AIDS defense shows promise.

PMID- 9560624
TI  - Possible HIV vaccine stirs hope.

PMID- 9560625
TI  - Local anesthesia for pediatric patients.

PMID- 9560626
TI  - The art of endodontics: selected case histories, Part 2.

PMID- 9560627
TI  - Microendodontic analysis of failure: identifying missed canals.

PMID- 9560628
TI  - A new approach to implant-supported overdentures.

PMID- 9560630
TI  - Taking responsibility for occlusion: the perfect occlusion.
AB  - Patients free from occlusal dysfunction rarely have their teeth together. But,
      when occlusion does occur (i.e., swallowing), the contacts should be simultaneous
      and in such a manner as to direct the vector of force down the long axis of the
      tooth or implant. The incline planes should not touch.

PMID- 9560629
TI  - Xerostomia: managing a complex condition. Interview by Phillip Bonner.

PMID- 9560631
TI  - Immediate gratification with laser perio/prosthetic teamwork.

PMID- 9560632
TI  - A surgeon's diary: the wounded and ill children of Vietnam.

PMID- 9560633
TI  - Building a high-tech practice from the ground up.

PMID- 9560634
TI  - Office design: the treatment area.

PMID- 9560635
TI  - Ergo space-positioning.

PMID- 9560636
TI  - The bottom line: the business of dental hygiene.

PMID- 9560637
TI  - Update on dentin bonding. Interview by Phillip Bonner.

PMID- 9560638
TI  - Current dental chemotherapeutics, Part 2.
AB  - Periodontal diseases are the result of bacterial infections. Antimicrobial and
      other chemotherapeutic agents are effective adjuncts to mechanical therapy in
      helping practitioners limit the progression of disease. Topical antimicrobials
      used as mouthrinses can control supragingival plaque. Studies demonstrate that
      irrigation devices enhance the effectiveness of antimicrobials. Antibiotics have
      been shown to be of value in treating juvenile periodontitis, and rapidly
      advancing and refractory periodontitis. The use of tetracyclines to promote
      healing by stabilizing collagen and the use of nonsteroidal anti-inflammatory
      drugs and prostaglandin inhibitors offer promise for controlling periodontal
      disease.

PMID- 9560639
TI  - Periodontal disease monitoring.

PMID- 9560640
TI  - Fundamentally changing soft tissue grafting.

PMID- 9560641
TI  - A method for maximum clinical control of contacts, aesthetics, and longevity.

PMID- 9560642
TI  - The effects of a CO2 laser on the healing of a bone defect.
AB  - This case report illustrates a potentially valuable application of the CO2 laser
      in periodontal surgery. An intrabony defect was treated with a bone allograft.
      During the 28-day postsurgical period, epithelialization of the wound was delayed
      by lasing the soft tissue over the bony defect at weekly intervals for 4 weeks.
      This procedure resulted in complete regeneration of the bone defect in this case.
      Controlled studies need to be carried out to determine if the use of the laser to
      retard epithelial downgrowth has a clinically significant effect on bone
      regeneration.

PMID- 9560643
TI  - Practicing implant dentistry profitably.
AB  - The success of dental implants has opened up countless treatment possibilities
      for restorative dentists to offer to their patients. Just as our clinical
      paradigms have had to change because of this new technology, so too must our
      paradigms concerning the way we communicate with our patients change if we are to
      get them to say "yes" to treatment that we know that they need. Success in
      clinical treatment using implants requires a systematic approach. A systematic
      approach to communicating with your patients will allow you to have the same high
      degree of success with treatment acceptance that is possible with dental
      implants. The key to the systems we have discussed is Relationship Centered Care.
      A relationship is fostered and enhanced through a Comprehensive Examination
      Process, a structured Consultation Process utilizing the influencing process and
      Financial Arrangements that allow the patient to receive what they want while the
      office maintains the profitability that it needs. A system for calculating
      rational fees can be utilized that allows the practice to have control over an
      area that traditionally was controlled by anecdotal factors. The Pride Institute
      has developed this material and is presenting it to the profession so that
      restorative dentists can truly practice implant dentistry profitably.

PMID- 9560644
TI  - An alternative provisional implant for immediate functional loading.

PMID- 9560645
TI  - Using copy milling technology in restorative dentistry.
AB  - A technique for the fabrication of copy milled ceramic restorations has been
      presented. Both direct and indirect fabrication techniques of inlays, onlays,
      veneers, and crowns are possible. A copy milling machine can mill accurately
      fitting restorations with a marginal gap of 50 microns. The machine uses
      premanufactured porcelain blanks, which have improved physical properties over
      conventional porcelains used in standard techniques. Recently, the ability to
      mill In-Ceram crowns from presintered alumina blocks and Spinell crowns from
      alumina/magnesia blocks has been added to the system. The copings are veneered
      with aluminous porcelain as in the conventional In-Ceram technique.

PMID- 9560646
TI  - Preparation of porcelain veneers: a new approach.

PMID- 9560647
TI  - Controversy in TMD: putting the issues in perspective.

PMID- 9560648
TI  - Hygiene partnering, Part 1.

PMID- 9560649
TI  - Rightsizing right now.

PMID- 9560650
TI  - Who is responsible for the schedule?
AB  - The focus of this has been to increase communication between the team. We have
      covered ways to stay true to the ideal day concept, to effectively capture
      details about patients who come in on short notice, and to prepare and update the
      day's list in a timely manner.

PMID- 9560651
TI  - Researchers develop AIDS-destroying viruses.

PMID- 9560652
TI  - Clinton sets goal for AIDS vaccine.

PMID- 9560653
TI  - Successful management of the gingival tissues for aesthetic restorative
      procedures.
AB  - A sage advisor once said, "Why is it that we (dentists) never seem to have the
      time to do all steps the first time around, but then find the time when something
      goes amiss?" Many of us are caught up in a prison called time that directly
      dictates our every move. We must be released from this mindset and rediscover the
      importance of patience and devotion to technique. That same wise man added, "The
      definition of a short cut is the longest distance between two points." The moral
      is time spent to gain tissue health will be returned a thousand fold. Cases will
      be completed with greater patient comfort and doctor satisfaction.

PMID- 9560654
TI  - Placing porcelain laminate veneers for function and aesthetics.

PMID- 9560655
TI  - Advances in restorative dentistry. Interview by Phillip Bonner.

PMID- 9560657
TI  - Is patient confirmation an adequate indicator of occlusal adjustment completion?

PMID- 9560656
TI  - Resin-bonded margins in direct posterior composites.

PMID- 9560659
TI  - Simple, cost-effective, cosmetic periodontal stabilization.

PMID- 9560658
TI  - Specialty endodontics: diagnostic challenges, Part 2.
AB  - Endodontic diagnosis and treatment can range from simple to extremely complex.
      But no matter how simple a case may seem, a thorough examination by the treating
      endodontist is imperative before any treatment is done. Taking the time to
      perform an examination in a consistent and methodical approach can rescue the
      patient from unnecessary treatment, and the treating dentist from potential
      liability. The patient may be frustrated from repeating many of the same tests
      performed by the referring dentist, but this situation can be resolved with clear
      communication from the general dentist and the endodontist as to the benefits of
      the endodontist's exam. With proper communication, patients will recognize that
      their general dentist and endodontist are concerned that they receive the best of
      care.

PMID- 9560660
TI  - Biotech in periodontics: molecular engineering yields new therapies.

PMID- 9560661
TI  - Power scalers: the new boom in contemporary periodontics.
AB  - The choice of which type of instrumentation to use remains the decision of the
      practitioner. It all depends on what goal the clinician hopes to achieve, the
      resources, and the physical set up within which they work. While speed in
      debridement, coupled with ease of use and comfort to the patient and practitioner
      are all important, the primary goal must always remain the optimal healing and
      success of the dental procedure. With improved tip designs and efficiency, power
      scaling has the ability to improve dental hygiene and periodontal care in the
      future.

PMID- 9560663
TI  - Ensuring dental practice success, Part 1.

PMID- 9560662
TI  - Practice building with halitosis treatment.

PMID- 9560664
TI  - Nonconfrontational case presentation: the seven laws of patient communication
      response.

PMID- 9560665
TI  - In search of the fountain of youth.

PMID- 9560666
TI  - Instant gratification for patients from laminate veneers.

PMID- 9560667
TI  - Bioesthetic guided tips: a new method for creating a youthful smile.

PMID- 9560668
TI  - Into the fourth dimension: news from the front as the millennium approaches.

PMID- 9560669
TI  - Nonsurgical endodontic retreatment.

PMID- 9560670
TI  - Oral rehabilitation: restoring the triad of health, function, beauty.

PMID- 9560671
TI  - Conservative technique for replacement of existing posterior bridges.

PMID- 9560672
TI  - The integration of dentistry and medicine: is it on the horizon?. Interview by
      Phillip Bonner.

PMID- 9560673
TI  - Genetic susceptibility to periodontal disease.

PMID- 9560674
TI  - Anterior space maintenance: aesthetics and function.

PMID- 9560675
TI  - The key to success: maintaining the long-term health of implants.
AB  - During the infancy years of dental implantology, the emphasis for long-term
      success of osseointegrated implants was the surgical phase of dental
      implantology. In the years that followed, the emphasis for success had switched
      from a purely surgical influence to focusing more on the proper fixture placement
      which would be dictated by the prosthetic and aesthetic needs of each particular
      case. In more recent years, the dental profession has recognized professional
      implant maintenance and diligent patient home care as two critical factors for
      the long-term success of dental implants. The microbiota and clinical
      presentation of peri-implantitis is the same as periodontitis around a natural
      tooth.

PMID- 9560676
TI  - A new condensable composite for the restoration of posterior teeth.
AB  - Undoubtedly the greatest resistance of clinicians to use composite resins in
      posterior teeth relates to technique sensitivity, time consumption, and
      complexity. Placing conventional posterior composite resins does not take into
      account that composites differ considerably from amalgam. This is particularly
      true with respect to its physical characteristics, especially insertion and
      packing properties. The development of a posterior composite resin that can be
      placed by an amalgam carrier and subsequently packed or condensed as an amalgam,
      should assist clinicians greatly in their ability to successfully restore class
      II cavity preparations. Acknowledgment is expressed to Bruce Small, DMD, for the
      clinical dentistry and slides.

PMID- 9560677
TI  - Scheduling the new patient exam and prophy, Part 2.

PMID- 9560678
TI  - Gingival bleeding: why it's critical and how to stop it.

PMID- 9560679
TI  - The consolidation of dentistry. Interview by Phillip Bonner.

PMID- 9560680
TI  - Restorative endodontics: anatomy of a failure.

PMID- 9560681
TI  - Endodontic overfills: good? Bad? Ugly?

PMID- 9560682
TI  - The art of endodontics: selected case histories, Part 3.

PMID- 9560683
TI  - Porcelain laminate veneers to improve aesthetics.

PMID- 9560684
TI  - Making the blues go away.

PMID- 9560685
TI  - A combination technique for nonvital bleaching.

PMID- 9560686
TI  - A new dimension in temporization.

PMID- 9560687
TI  - The growth of nonsurgical treatment of periodontitis. Interview by Randall L.
      Valentine.

PMID- 9560688
TI  - Smarter and cheaper X-rays. Pushing the limits in digital radiography.

PMID- 9560689
TI  - Laser bleaching: a clinical survey.

PMID- 9560690
TI  - Occlusion and implants.

PMID- 9560692
TI  - Understanding the Internet.

PMID- 9560691
TI  - Current trends in dental benefits plans: 1997.

PMID- 9560693
TI  - Creating the ideal patient and chart flow structure.

PMID- 9560694
TI  - Math versus myth: dispelling legendary management precepts.

PMID- 9560695
TI  - Genetic defect wards off AIDS infection, say researchers.

PMID- 9560696
TI  - Thalidomide heals AIDS-related mouth ulcers.

PMID- 9560697
TI  - Fiber-reinforced restorative materials bring new treatment options. Interview by
      Phillip Bonner.

PMID- 9560699
TI  - Porcelain laminates: new insights from hindsight.

PMID- 9560698
TI  - Crown torquing severely worn incisors to gain clearance for crowns.

PMID- 9560700
TI  - To prep or not to prep.

PMID- 9560701
TI  - A no-metal, no-mercury, full-mouth smile recovery.

PMID- 9560702
TI  - Using flowable composites in direct posterior restorations.

PMID- 9560703
TI  - Clinical, radiographic indicators of a pending difficult extraction.

PMID- 9560704
TI  - A long-span, acid-etched, fixed partial denture.

PMID- 9560705
TI  - Salvaging of adjacent fixed partial dentures using an overcasting technique.
AB  - Occasionally, clinicians are faced with a situation in which a solitary tooth
      between two bridges requires extraction. When this type of situation occurs, we
      must ponder the dilemma of how to replace the missing tooth. Options include
      placing an implant where the tooth was extracted or remaking one large multiunit
      bridge. Implants are not always possible or practical, and remaking a multiunit
      bridge that involves the abutments of the two existing bridges can be challenging
      and becomes much more expensive to the patients. The overcasting technique is a
      treatment modality that offers a solution in these particular situations.

PMID- 9560706
TI  - Maximizing the practice potential of hygiene.

PMID- 9560707
TI  - The best marketing tool ever invented....

PMID- 9560708
TI  - Scheduling stress-free emergencies.

PMID- 9560709
TI  - 31 financial check-off points.

PMID- 9560710
TI  - Know your market and present the case.

PMID- 9560711
TI  - AIDS deaths decline in the US for first time.

PMID- 9560712
TI  - New developments in composite resins. Interview by Phillip Bonner.

PMID- 9560713
TI  - The art of tooth preparation and recontouring.

PMID- 9560714
TI  - Intraoral porcelain repairs with composite.

PMID- 9560715
TI  - Heated bleaching: a safe and rewarding method.

PMID- 9560716
TI  - Facial rehabilitation: maximizing aesthetics through a coordinated team approach.

PMID- 9560717
TI  - Cosmetic rehabilitation after dental trauma. A conservative approach.

PMID- 9560718
TI  - Benefit-driven treatment planning. Fiber-enhanced periodontal therapy.

PMID- 9560719
TI  - Calculus and coronary artery disease.

PMID- 9560720
TI  - TMJ disorders and their relationship to occlusion and dental compression
      syndrome.

PMID- 9560721
TI  - An alternative approach to bonding and pulpal protection.

PMID- 9560722
TI  - Conservative anterior reconstruction: a combined technique approach.

PMID- 9560723
TI  - Predicting bleaching results with computer imaging.
AB  - Vital bleaching can be a relatively unpredictable treatment. Photographs of
      previous cases and cosmetic imaging, although useful, may lead to unrealistic
      expectations on the part of the patient. The high-tech mystique of computer
      imaging and viewing one's own teeth has a significant impact on the dental
      patient. Whether imaged by the dentist or an auxiliary, patients must be aware of
      alternatives that may exist both before and during treatment. Cosmetic imaging
      should be used as an adjunct to, not as the prime motivator for, treatment
      planning in bleaching cases. Excellent communication between the practitioner and
      patient is the most important factor in assuring positive bleaching results and
      patient satisfaction.

PMID- 9560724
TI  - Intraoral cameras: dentistry's pursuit of wow.

PMID- 9560725
TI  - Revitalizing PFM restorations with porcelain veneers.

PMID- 9560726
TI  - Integrating computers: a front line perspective.

PMID- 9560727
TI  - Hygiene partnering, Part 2.
AB  - Today's technology is full of magic and delight in the hygiene arena. Throughout
      the years, dental hygiene has shifted into a thriving career, and hygienists have
      welcomed the new role with open arms. Innovation, technology, and partnering have
      also taken the concept of codiagnosis and comprehensive care to a higher level in
      the hygiene department. These benefits, combined with more sophisticated patient
      centered communication skills and team-centered management philosophies will,
      without doubt, secure the future of dental hygiene departments in practices
      worldwide. Moreover, smart practices remaining committed to attracting, training,
      and retaining only high-caliber staff with interdependent, overlapping talent
      will find the most reward in helping their patients achieve and maintain optimum
      oral health for a lifetime.

PMID- 9560728
TI  - Doctors plan to inject themselves with live AIDS vaccine.

PMID- 9560729
TI  - The bonded tooth-colored onlay.

PMID- 9560730
TI  - Enamel microabrasion: is it still a viable procedure?

PMID- 9560731
TI  - Two front teeth: a common cosmetic dilemma.

PMID- 9560732
TI  - Fiber-reinforced composite bridge. Inlay-to-inlay technique.

PMID- 9560733
TI  - Anhydrous glass technique.

PMID- 9560734
TI  - Update on pain management. Interview by Phillip Bonner.

PMID- 9560735
TI  - An analysis of dental pain for better oral health.

PMID- 9560736
TI  - Macrolide antibiotics.
AB  - The macrolides remain excellent antibiotics for many infections particularly
      those involving intracellular and/or respiratory pathogens. Erythromycin is still
      an effective drug for many acute orofacial infections. The newer macrolides,
      azithromycin and clarithromycin, should also prove efficacious although there is
      very little current data on their use in orofacial infections. They have the
      advantages over erythromycin of less GI toxicity, higher tissue concentrations,
      greater gram-negative spectrum, and once or twice daily dosing for better patient
      compliance. Macrolide concentration in inflammatory cells and transport to the
      site of infection is a distinct advantage over other antibiotics. Both
      erythromycin and clarithromycin are associated with significant drug interactions
      but azithromycin is devoid of such potential toxicity. Azithromycin is less
      effective against gram-negative cocci than erythromycin and clarithromycin and
      attains very high tissue concentrations for a very long time, but whether either
      of these characteristics is clinically significant for orofacial infections is
      presently unknown.

PMID- 9560737
TI  - Periodontal laser surgery.
AB  - A gingivectomy performed with a laser is a short, easy procedure that produces an
      immediately dramatic effect. Compared to a scalpel gingivectomy, there is
      excellent hemostasis, which improves visualization, requires less need for
      periodontal packing, and results in minimal postoperative discomfort. Tissue
      rebound also is minimal. Use of lasers requires specific training. The only
      approved function in periodontics at this time according to the American Academy
      of Periodontology is soft tissue surgery. Some periodontal applications include
      frenectomy, soft tissue crown lengthening, distal wedge procedures, soft tissue
      tuberosity reductions, gingivectomy, gingivoplasty, stage II of implants,
      operculectomies, biopsies, coagulation of graft donor sites, hemorrhage disorder
      patients, and stripping procedures for various leukoplakias.

PMID- 9560738
TI  - Endodontic re-treatment perspective: cone fit is key to unlocking the power of
      hydraulics.

PMID- 9560739
TI  - A surgeon's diary: Washington, DC of the '60s.

PMID- 9560740
TI  - Using cross-sectional tomography to perform exploratory radiography in lieu of
      exploratory surgery.
AB  - Preoperative treatment planning for dental implants is crucial to their
      integration and especially prosthetic rehabilitation. Exploratory radiography is
      an essential component of treatment planning. Radiographic examination using
      cross-sectional tomography as an adjunct to panoramic radiographs can
      significantly decrease the incidence of exploratory surgery that could result in
      unplanned bone augmentation procedures due to insufficiency in alveolar bone
      height, width, quantity, quality, and will not allow proper aesthetic prosthetic
      rehabilitation subsequent to improper implant placement.

PMID- 9560741
TI  - A week in the life of a type-A high-tech practice.

PMID- 9560742
TI  - Ten ways to ensure dental practice success, Part 2.

PMID- 9560743
TI  - Statistical monitoring of the dental practice.

PMID- 9560744
TI  - Effective use of tungsten carbides for restorative dentistry.

PMID- 9560745
TI  - Clinical application of power Doppler imaging to visualize coronary arteries in
      human beings.
AB  - Supplementation of angiographic information during bypass procedures is an
      attractive goal for the echocardiographic researcher. Compared with color flow
      mapping, power Doppler imaging is superior in terms of identifying small vessels
      and noise suppression because of the use of Doppler signal strength for imaging.
      Although power Doppler imaging does not provide information about flow velocity
      or its direction, it does show detailed vessel flow in a static organ. Our study
      was designed to obtain angiographic images of the coronary artery by the use of
      power Doppler imaging in 31 patients during open heart surgery. During cold
      cardioplegic infusion, the epicardial coronary artery and the coronary artery
      within myocardium, such as the septal perforator, could be well visualized by
      power Doppler imaging. There was good correlation between the diameters of
      coronary arteries measured from power Doppler imaging and those from quantitative
      coronary angiography (r = 0.964, p < 0.0001). We obtained clear and accurate
      images of the coronary artery by using power Doppler imaging during cardiac
      standstill. These images might provide meaningful supplemental information to the
      operator, such as confirming the target coronary artery during the cardioplegia
      and choosing the appropriate arterial portion for a bypass operation.

PMID- 9560746
TI  - Detection of myocardial perfusion defects by contrast echocardiography in the
      setting of acute myocardial ischemia with residual antegrade flow.
AB  - Although myocardial contrast echocardiography accurately demarcates area at risk
      during total coronary occlusion, the ability of MCE to delineate area at risk in
      the presence of residual antegrade flow is unknown. We hypothesized that
      perfusion defects in myocardial segments supplied by severe coronary stenoses
      with residual antegrade flow could be detected by MCE using intravenous FS069. We
      studied 13 open-chest dogs using an intravenous injection of FS069 during
      intermittent harmonic imaging. Images were collected at baseline, during acute
      ischemia with residual antegrade flow, physiologic hyperemia (release of
      stenosis), and total coronary occlusion. Regional myocardial blood flow was
      assessed using colored microspheres. MCE risk area during acute ischemia with
      residual antegrade flow and total occlusion was planimetered and compared with
      pathologic risk area (area unstained by monastral blue). Background-subtracted
      peak videointensity in the risk area was assessed for all flow states. Regional
      myocardial blood flow confirmed expected flow states, being significantly greater
      during physiologic hyperemia (4.16 +/- 1.22 ml/min/g) than at baseline (0.71 +/-
      0.19 ml/min/g) and significantly diminished during coronary stenosis with
      residual antegrade flow (0.20 +/- 0.16 ml/min/g) and total occlusion (0.09 +/-
      0.06 ml/min/g; p < 0.0001). Myocardial risk area by MCE during coronary stenosis
      with residual antegrade flow correlated well with pathologic risk area determined
      by monastral blue staining (r = 0.86). Peak videointensity during coronary
      stenosis (111 +/- 27) was significantly less than at baseline (157 +/- 50) but
      greater than during total occlusion (81 +/- 34; p < 0.0001). In conclusion,
      intravenous FS069 in conjunction with intermittent harmonic imaging delineates
      area at risk in ischemic myocardium supplied by a coronary stenoses with residual
      antegrade flow. The presence of a perfusion defect on MCE does not necessarily
      imply that the coronary artery is totally occluded.

PMID- 9560747
TI  - Reduced test time by early identification of patients requiring atropine during
      dobutamine stress echocardiography.
AB  - In a randomized, controlled clinical trial, we evaluated the ability of an
      algorithm to identify, before peak stress, patients who will ultimately require
      atropine during dobutamine stress echocardiography. The effects of early atropine
      administration on test duration, atropine dose, dobutamine dose, and heart rate
      response also were studied. Compared with conventional atropine administration at
      peak dobutamine infusion, early atropine administration reduced test duration 8%
      (1.1 minutes, p = 0.02) and total dobutamine use 11% (0.41 mg/kg, p = 0.02) but
      required 90% more atropine (0.36 mg, p < 0.001). Conventional atropine
      administration resulted in a late, rapid rise in both heart rate and rate
      pressure product. However, the heart rate and rate-pressure product curves for
      patients receiving early atropine paralleled those seen in patients not requiring
      atropine during dobutamine stress echocardiography. In conclusion, early atropine
      administration provides a more balanced stress and reduces test duration, thus
      decreasing total exposure to dobutamine and potentially increasing test
      efficiency.

PMID- 9560748
TI  - Three-dimensional imaging in aortic disease by lighthouse transesophageal
      echocardiography using intravascular ultrasound catheters. Comparison to three
      dimensional transesophageal echocardiography and three-dimensional intra-aortic
      ultrasound imaging.
AB  - Two-dimensional (2D) transesophageal echocardiography (TEE) and 2D intravascular
      ultrasound (IVUS) imaging face their greatest limitation in visualizing aortic
      disease in patients. With the aid of three-dimensional (3D) image reconstruction,
      TEE and IVUS can potentially overcome this limitation but still provide only
      limited spatial appreciation in aortic disease because 3D imaging of the thoracic
      aorta requires a broader spatial visualization of the mediastinum than provided
      by both techniques. Moreover, for timely decision making about aortic disease TEE
      is limited by a large probe, which requires sedation. Therefore, we developed an
      approach called 3D lighthouse transesophageal echocardiography (LTEE) using a
      thin intravascular ultrasound catheter, which provides a full circumferential
      (360 degree) image and requires no sedation. The purpose of this study was to
      compare the feasibility and accuracy of 3D TEE, 3D IVUS, and 3D LTEE for
      obtaining spatial visualization of the thoracic aorta to detect aortic diseases
      in patients. 3D image datasets were obtained for 3D LTEE by a manual pullback of
      a 3.3 mm thick, 10 MHz intravascular ultrasound catheter positioned in the
      esophagus; for 3D TEE using a conventional 15 mm thick probe; and for 3D IVUS
      using a 2.6 mm thick, 20 MHz intravascular ultrasound catheter. In 12 consecutive
      patients, three with aortic dissection (two with type III, one with type I) and
      11 with suspected artherosclerosis, we analyzed and compared spatial
      visualization of the thoracic aorta, 3D image quality, patient discomfort, and
      study time. Providing a 3D dataset of 360-degree tomographic images of the
      mediastinum, 3D LTEE was the only approach that allowed broad spatial
      visualization of the aortic arch (9 of 12 patients) with the detection of aortic
      dissection or atherosclerotic plaques. Spatial visualization of the aortic arch
      by 3D TEE was incomplete because of the relatively narrow 90-degree image sector.
      However, in other segments 3D image quality by 3D TEE was superior to 3D LTEE and
      3D IVUS. Because of the thin catheter, patient discomfort (p < 0.0001) and
      examination time (p = 0.015) were significantly less for 3D LTEE compared with 3D
      TEE. 3D LTEE is a promising new technique for 3D imaging of the thoracic aorta
      and detection of aortic disease with improved spatial visualization and reduced
      patient discomfort compared with 3D TEE and 3D IVUS.

PMID- 9560749
TI  - Progressive enlargement of the regurgitant orifice in patients with chronic
      aortic regurgitation.
AB  - The severity of aortic regurgitation is dependent on the size of the regurgitant
      orifice, the left ventricular response to volume overload, and the diastolic
      pressure difference across the aortic valve. The purpose of this study was to
      test the hypothesis that the aortic regurgitant orifice increases over time in
      patients with audible chronic aortic regurgitation. To assess serial changes in
      aortic regurgitant severity by the use of two-dimensional and Doppler
      echocardiography, 59 patients (29 men and 30 women) with audible chronic aortic
      regurgitation were prospectively identified and evaluated annually with two
      dimensional and Doppler echocardiograms. Patients were followed for a median of
      38 months. We measured two separate indicators of the size of the regurgitant
      orifice: the color Doppler regurgitant jet width and the Doppler-derived
      regurgitant orifice area. Jet width increased with time (0.5 +/- 0.4 cm at
      baseline, 0.04 +/- 0.01 cm/year slope, p < 0.001). The regurgitant orifice area
      also increased (0.12 +/- 0.14 cm2 at baseline, 0.01 +/- 0.01 cm2/year, p = 0.05).
      Changes in regurgitant orifice area were related to changes in left ventricular
      end-diastolic dimension (p < 0.001). There were no significant changes in left
      ventricular chamber dimensions, volumes, and regurgitant volume over time in this
      cohort. Increases in jet width and orifice area occurred in patients with all
      degrees of baseline disease severity, with bicuspid or tricuspid leaflet
      morphology, and with male or female sex. In this prospective study of chronic
      aortic regurgitation, both jet width and Doppler-derived regurgitant orifice area
      increased over time. These findings suggest that one factor in the progression of
      chronic aortic regurgitation is enlargement of the orifice.

PMID- 9560750
TI  - In vitro analysis of regurgitant fraction using Doppler power-weighted sum of
      velocities.
AB  - The power-weighted sum of velocities (PWS) is the sum of each velocity component
      of the Doppler signal multiplied by its power. The purpose of this study was to
      determine (1) whether PWS is linearly related to volume flow and (2) whether PWS
      can predict the regurgitant fraction in an in vitro pulsatile flow system
      simulating aortic regurgitation. Doppler analysis of aortic flow was performed
      with an intact valve and two regurgitant valves. For each valve a linear relation
      between the forward flow PWS and forward flow volume was demonstrated, with
      excellent correlation (r = 0.99). For the valves with regurgitant orifices, the
      values for the PWS-derived regurgitant fraction were compared with measured
      regurgitant fraction. A fair correlation was demonstrated (r = 0.59), with low
      accuracy in prediction (error 44% +/- 24%). The PWS was inaccurate in predicting
      flow ratios in our in vitro system despite the strong relation with forward flow
      volume. The error incurred may be due to effects of filters that remove low
      velocity and low amplitude information.

PMID- 9560751
TI  - Reversible left atrial dysfunction possibly due to afterload mismatch in patients
      with left ventricular dysfunction.
AB  - Limited data are available concerning the influence of altered loading conditions
      on left atrial (LA) function. In addition, the underlying mechanism of the
      augmentation of atrial filling (A) velocity (assessed by transmitral Doppler
      measurement) after treatment of heart failure has been less studied. Therefore,
      we examined various indexes of LA function during the depression of left
      ventricular (LV) filling pressure resulting from treatment of heart failure.
      Twelve patients with LV dysfunction (ejection fraction < 50%) underwent right
      heart catheterization and transthoracic echocardiography before and after optimal
      treatment of heart failure. LV/LA volume and ejection fraction and mitral and
      pulmonary venous flow velocities were measured. LV stiffness (substitute for LA
      afterload) was assessed by the ratio of LV filling pressure to LV end-diastolic
      volume. After treatment of heart failure, the mitral A velocity significantly
      increased (38 +/- 9 to 58 +/- 16 cm/sec, p < 0.005) and there was a distinct
      attenuation of the difference of the pulmonary venous and mitral A-wave duration
      (43 +/- 29 to -8 +/- 31 msec, p < 0.005). These findings were associated with a
      marked decrease in LV stiffness (0.12 +/- 0.04 to 0.05 +/- 0.02 mm Hg/ml, p =
      0.0001) and an increase in LA ejection fraction (27% +/- 7% to 38% +/- 8%, p <
      0.005). There was a significant curvilinear relation between LA ejection fraction
      and LV stiffness (r = 0.63, p < 0.01). The mitral A velocity correlated
      positively with LA ejection fraction (r = 0.77, p < 0.0001) and inversely with LV
      stiffness (r = -0.52, p < 0.01). The reversible LA dysfunction suggests that the
      initial LA dysfunction is due to LA afterload mismatch rather than intrinsic LA
      disease, which also contributes to the augmentation of the mitral A velocity
      after heart failure treatment.

PMID- 9560752
TI  - Effect of sample volume location on Doppler-derived transmitral inflow velocity
      values in 288 normal subjects 20 to 80 years old: an echocardiographic, two
      dimensional color Doppler cooperative study.
AB  - The aims of the study were to evaluate in a population of 288 normal subjects 20
      to 80 years old (1) the normal values of the indexes of the mitral flow velocity
      pattern measured either at the tips of the mitral leaflets or at the annulus; (2)
      whether there was a significant difference between the values obtained at the
      tips compared with those measured at the mitral annulus; (3) the correlation with
      aging between the indexes measured in the two different positions; and (4)
      whether certain physiological variables have different effects on diastolic
      function measured in the two different positions. The highest values were always
      measured at the tips of the mitral leaflets (p < 0.05); only atrial filling
      fraction, E acceleration time, and E deceleration velocity had higher values when
      measured at the level of the annulus (p < 0.05). The A-wave peak velocity had the
      same mean value when measured at both the tips and at the annulus. A significant
      difference in the correlation between parameters measured at the tips of the
      mitral leaflets with age and at the annulus (with age) was observed for the
      following parameters: (1) peak E velocity, E integral, total integral and E
      acceleration showed better correlation with age when measured at the annulus (p <
      0.02); (2) peak A velocity and A integral showed better correlation with age when
      measured at the tips of the mitral leaflets (p < 0.001). Multivariate analysis
      showed that age was the variable that had the most influence on diastolic
      function parameters; heart rate had less influence on the diastolic function
      indexes.

PMID- 9560753
TI  - Echocardiographic spectrum of supracardiac total anomalous pulmonary venous
      connection.
AB  - Although infracardiac total anomalous pulmonary venous connection (TAPVC) is
      almost always associated with venous obstruction, the incidence and location of
      obstruction in supracardiac TAPVC has not been completely delineated. This report
      summarizes our experience with 20 cases of supracardiac TAPVC diagnosed by
      transthoracic echocardiography from Jan. 1989 to Mar. 1997. Fifty percent were
      obstructed, and five different sites of narrowing were found. The most common
      sites of obstruction were at the level of the left pulmonary artery (left
      vertical vein) and at the insertion into the superior vena cava (right vertical
      vein). Because nonobstructed Doppler flow patterns are present proximal to the
      actual site of obstruction in the anomalous pathway, a thorough interrogation of
      the entire venous channel with two-dimensional and Doppler echocardiography is
      essential to provide complete preoperative anatomic and hemodynamic details to
      determine the nature and timing of surgery in this condition.

PMID- 9560754
TI  - Echocardiography in the diagnostic evaluation of syncope.
AB  - To assess the role of echocardiography in patients with syncope, we studied 439
      consecutive adults who were referred over a 7-year period. Of all patients, 251
      (57.2%) were women, who were generally younger than male referrals. All 439
      patients had interpretable echocardiographic studies. Results showed that of
      patients younger than 40 years of age, 72.8% had scans that were normal and 18.5%
      had mitral valve prolapse (MVP). All (other) patients in this age group with
      abnormal echocardiographic findings (8.7%) had either abnormal physical findings
      over the heart, an abnormal electrocardiogram, or an abnormal chest radiograph.
      In patients 60 years old and older, 29.6% had scans interpreted as normal and
      4.6% had MVP (approximately half of these patients had at least moderate mitral
      regurgitation). The study demonstrates that patients younger than 40 years of age
      with syncope are likely to have a normal Doppler echocardiography or MVP without
      significant mitral regurgitation. Thus additional abnormal findings (e.g., heart
      murmur, abnormal electrocardiogram, or abnormal chest radiograph) may be needed
      before the patient is referred to the echocardiography laboratory.

PMID- 9560755
TI  - Cerebrovascular emboli related to pulmonary venous thrombosis after lung
      transplantation.
AB  - We describe a case of cerebral emboli related to pulmonary venous thrombosis
      after bilateral lung transplantation in a young man with cystic fibrosis. The
      diagnosis was made by transesophageal echocardiography, leading to aggressive
      anticoagulation within 24 hours of surgery. Hemodynamic deterioration in the
      following hours was of concern for the development of obstructive thrombus but
      was found to be due to pericardial tamponade, which, remarkably, resolved during
      a repeat transesophageal echocardiography.

PMID- 9560756
TI  - Pseudoaneurysm of the ascending aorta after aortic valve replacement.
AB  - A 58-year-old man with fever and chest wall tenderness was seen 8 weeks after
      aortic valve replacement. His initial postoperative course had been complicated
      by mediastinitis, requiring antibiotics and surgical debridement. A transthoracic
      echocardiogram did not reveal the culprit lesion. Pseudoaneurysm of the ascending
      aorta was suspected, based on computerized tomographic and magnetic resonance
      images of the chest. Intraoperative transesophageal echocardiography confirmed
      the diagnosis of pseudoaneurysm and was a key component in the patient's
      operative management.

PMID- 9560757
TI  - Echocardiography allows early detection and long-term survival after infarct free
      wall rupture.
AB  - Approximately one third of free wall infarct ruptures are subacute and
      theoretically accessible for surgery. Two-dimensional echocardiography is an
      important tool in the early diagnosis of cardiac rupture. We report the
      successful treatment of a 74-year-old woman with subacute free wall rupture, who
      is still alive 3 years after surgery.

PMID- 9560758
TI  - Unusual structural abnormality in a biplane transesophageal transducer with
      normal imaging function.
AB  - We encountered a case of an unusual structural abnormality in a biplane
      transesophageal echocardiography transducer. One of the steel wires making up the
      flexion cable responsible for anterior flexion was ruptured with one end piercing
      through the sheath, and this defect did not affect the imaging function of the
      transducer. Measures to detect this defect should be incorporated into the
      routine care of the transesophageal transducer.

PMID- 9560759
TI  - Veterinary randomized clinical trial reporting: a review of the small animal
      literature.
AB  - The randomized clinical trial (RCT) is a valuable research method for the
      evaluation of new treatment and prevention regimens in veterinary medicine.
      Reporting of clinical trials in other disciplines has not been complete. Without
      complete information on the conduct and results of a clinical trial, readers
      cannot optimize their use of the information presented. This report represents an
      objective review of randomized clinical trials in the veterinary small animal
      literature from 1986 to 1990. Results indicate that RCT reports in the small
      animal veterinary literature are incomplete. The importance of reporting on
      particular aspects of RCT research is described.

PMID- 9560760
TI  - Granulocytic ehrlichiosis in dogs from North Carolina and Virginia.
AB  - Medical records of 3 dogs from North Carolina and 3 dogs from Virginia with
      ehrlichial morulae in circulating neutrophils were studied retrospectively. Two
      clinically distinct disease syndromes, including chronic, moderate to severe
      anemia (n = 3) and polyarthritis (n = 2) were associated with canine granulocytic
      ehrlichiosis (CGE) in these dogs. One dog was clinically healthy, and
      abnormalities were not detected during physical examination. Clinical signs were
      nonspecific and included fever, lethargy, anorexia, vomiting, and diarrhea. The
      most frequent laboratory abnormalities were normocytic normochromic
      nonregenerative anemia, moderate thrombocytopenia with large platelets,
      lymphopenia, and eosinopenia. Considerable variability was found in the serologic
      responses to Ehrlichia equi, Ehrlichia canis, and Ehrlichia chaffeensis antigens
      among the 5 dogs for which stored sera were available for indirect fluorescent
      antibody testing. Polymerase chain reaction amplification and sequencing of
      portions of the 16S rRNA gene from blood (collected in ethylenediaminetetraacetic
      acid) of 1 severely anemic dog (dog 3) and 1 polyarthritic dog (dog 4) resulted
      in DNA sequences nearly identical to the GenBank accessions for Ehrlichia
      ewingii. The DNA sequence from a 3rd dog (dog 5) was most similar to that of E.
      canis. Serologic or molecular results support the possibility of E. ewingii, E.
      equi, and E. canis coinfection or serologic cross-reactivity among canine
      granulocytic and monocytic Ehrlichia species in dogs from North Carolina and
      Virginia. Variability in response to tetracycline or doxycycline treatment was
      noted in these dogs, with more rapid resolution of signs in dogs with
      polyarthritis. We report the 1st cases of CGE in dogs from North Carolina and
      Virginia, including recognition of CGE in a healthy dog.

PMID- 9560761
TI  - Coagulation abnormalities in 22 cats with naturally occurring liver disease.
AB  - Twenty-two cats with liver disease were evaluated for coagulation abnormalities
      including alterations in prothrombin time, activated partial thromboplastin time,
      thrombin time, factor VII activity, and platelet count. The purpose of the study
      was to determine the prevalence of coagulation abnormalities in this population
      of cats, classify abnormalities according to underlying pathogenesis, and
      determine if serum biochemical parameters typically used as indicators of liver
      disease showed any correlation with the coagulation abnormalities present. Study
      results indicated that at least 1 coagulation abnormality was present in 82% of
      the cats. Prolongation of prothrombin time was most common (16/22 cats) and
      factor VII activity was below reference range (< 60%) in 15 cats. When classified
      according to underlying pathogenesis, vitamin K deficiency was the most common
      abnormality found (11/22). Other abnormalities were less common and included
      hepatic synthetic failure (3/22), indeterminate (3/22), and disseminated
      intravascular coagulation (1/22). Increase in alkaline phosphatase (ALP) activity
      was the only biochemical abnormality that showed statistically significant
      correlation with coagulation abnormalities (P = .023). Cats with marked increases
      in ALP activity were more likely to have coagulation abnormalities than those
      with only mild increases in ALP activity.

PMID- 9560762
TI  - Results of quantitative cultures of urine by free catch and catheterization from
      healthy adult horses.
AB  - Quantitative urine cultures were performed on 11 male and 11 female healthy adult
      horses. Urine was collected by free catch and catheterization using standard
      methods. Results showed that all samples collected by free catch contained less
      than 20,000 colony-forming units (CFU)/mL. All samples collected by
      catheterization contained 500 CFU/mL or less. A significant difference was found
      between collection methods (P < .005), with catheterization having less
      contamination. In samples collected by free catch, females had significantly
      greater contamination than did males (P < .03). Predominant bacterial species
      isolated included Streptococcus spp., Escherichia coli, Enterobacter sp.,
      Bacillus sp., Staphylococcus spp., Diptheroids sp., Proteus spp., and
      Enterococcus sp. Many samples contained multiple bacterial species. Bacterial
      isolates were representative of the normal bacterial flora of the equine
      urogenital tract. This paper establishes reference values for quantitative urine
      culture results in healthy adult horses to aid in the diagnosis of urinary tract
      infections.

PMID- 9560763
TI  - Use of serum protein concentration to predict mortality in mixed-source dairy
      replacement heifers.
AB  - The relationship between serum protein concentration in the 1st week of life and
      survival to 16 weeks of age was examined in 3,479 Holstein replacement heifers
      over a period of 10 years on a farm with endemic salmonellosis. Thirty-four
      percent of calves studied had serum protein concentrations < 5.0 g/dL and 60.5%
      of calves had serum protein concentrations < 5.5 g/dL. Cumulative mortality was
      7.9%, indicating that calves with marginal passive transfer status can be reared
      successfully under conditions of endemic salmonellosis. Optimal survival was
      observed in calves with serum protein concentrations > 5.5 g/dL. Calves with
      serum protein concentrations of 5.0-5.4 g/dL had only a slightly increased
      relative risk (RR) of mortality (RR = 1.3) compared to calves with serum protein
      concentrations > 5.5 g/dL. The highest RR was experienced by calves with serum
      protein concentrations < 4 g/dL (RR = 4.6) and 4.0-4.4 g/dL (RR = 3.1). Calves
      with inadequate passive transfer (serum protein concentration < 5.0 g/dL),
      experienced increased mortality until at least 10 weeks of age, indicating that
      failure of passive transfer has an effect on calf health that extends into the
      juvenile period. Models in which serum protein concentration was treated with as
      a continuous variable or as a categorical variable failed to demonstrate any
      significant interaction between baseline mortality and the RR of mortality. This
      finding suggests that the RR derived in the present study should be applicable to
      farms with dramatically different baseline mortality rates.

PMID- 9560764
TI  - Efficacy of fresh-frozen plasma and cryoprecipitate in dogs with von Willebrand's
      disease or hemophilia A.
AB  - Here we report the comparative efficacy of fresh-frozen plasma (FFP) and
      cryoprecipitate in the treatment of 2 inherited bleeding disorders in dogs. The
      dogs were divided into 3 groups, consisting of 4 Doberman Pinschers with type I
      von Willebrand's disease (vWD) (group 1), 1 Scottish Terrier with type III vWD
      (group 2), and 4 German Shepherd Dogs with hemophilia A (group 3). In vWD,
      therapeutic efficacy was determined by the ability of the products to increase
      von Willebrand factor antigen (vWf:Ag) concentrations above 35 canine units
      (CU)/dL and to correct the prolonged buccal mucosal bleeding time. Therapeutic
      efficacy in hemophilia A was assessed by the ability of the products to increase
      the factor VIII coagulant (FVIII:C) activity above 30 CU/dL. In both groups 1 and
      2, higher increases in vWf:Ag were achieved with cryoprecipitate than with FFP,
      despite a significantly smaller total amount of vWf:Ag (in CU) being infused with
      cryoprecipitate. The maximum vWf:Ag attained after infusion in group 1 was
      dependent on both the baseline vWf:Ag concentration and on the type of infusion
      product. The dogs with vWD in both groups also displayed a delayed increase in
      FVIII:C activity after infusion of both plasma products, which is characteristic
      of the disease. In group 3, cryoprecipitate achieved similar increases in FVIII:C
      activity compared to FFP, although a significantly lesser amount of FVIII:C (in
      CU) was delivered with cryoprecipitate. Six of the 9 dogs treated with FFP
      experienced adverse effects ranging from mild pruritus to pallor and weakness,
      whereas none of the 9 dogs treated with cryoprecipitate had any observable
      adverse reactions (P = .009). Based on its efficacy and safety, we recommend
      cryoprecipitate over FFP for treatment or prophylaxis of hemorrhagic episodes in
      dogs with vWD or hemophilia A.

PMID- 9560765
TI  - Comparison of some pharmacokinetic parameters of 5 angiotensin-converting enzyme
      inhibitors in normal beagles.
AB  - This study was designed to determine the degree of inhibition of the angiotensin
      converting enzyme (ACE) in 5 normal dogs given single doses of conventionally
      used ACE inhibitors (ACEis). In addition the time required for that inhibition to
      return to 50% of the difference between maximum and zero (control values) was
      measured as an estimate of duration of action. The 5 ACEis (with dosages given in
      parentheses) were benazapril (0.5 mg/kg), captopril (2.0 mg/kg), enalapril (0.5
      mg/kg), lisinopril (0.5 mg/kg), and ramipril (0.25 mg/kg). Blood samples for ACE
      activities were obtained before dosing and at 1.5, 3.0, 6.0, 12.0, and 24.0 hours
      after dosing. All ACEis except captopril decreased ACE activities to
      approximately 25% of control by the 1.5- to 3.0-hour sample, and ACE activities
      returned to 50% of the difference by the 12-hour sample. The value of AVE
      activity returned to normal by 24 hours for benazapril, whereas values for ACE
      activity remained below normal for enalapril, lisinopril, and ramipril at 24
      hours. For captopril, however, ACE levels decreased to approximately 80% of
      control by the 1.5-hour recording, and returned to levels not different from
      control by the 3-hour recording. Based upon this study performed on normal dogs
      given a single dose, no pharmacokinetic advantage or disadvantage is apparent for
      any ACEi except captopril, which, at the dosage used, decreased ACE levels to a
      much lesser degree and shorter time.

PMID- 9560766
TI  - Possible late potentials in 4 dogs with sustained ventricular tachycardia.
AB  - Signal-averaged electrocardiograms (SAEKGs) were performed on 4 dogs with
      sustained ventricular tachycardia. Quantitative and qualitative analyses of
      SAEKGs were consistent with the presence of late potentials. Two of the 4 dogs
      subsequently died suddenly, and ventricular tachycardia and ventricular
      fibrillation were observed in 1 dog. High-frequency QRS durations (75-90
      milliseconds), duration of low amplitude (less than 40 microV) signals during the
      terminal QRS complex (LAS40) (28-40 milliseconds), root mean square voltages of
      the terminal 40 milliseconds of the QRS complex (RMS40) (124-6.5 microV), and
      root mean square voltages of the terminal 30 milliseconds of the QRS complex
      (RMS30) (13-2.1 microV) differed from results obtained in 68 of 70 control dogs.
      Echocardiographic data suggested dilated cardiomyopathy in 2 dogs and the cause
      of the arrhythmia in 2 dogs was not determined. The SAEKG may be a useful adjunct
      in identifying a subset of dogs with ventricular tachyarrhythmias that are at
      high risk for sustained ventricular tachycardia and sudden death. The
      sensitivity, specificity, and predictive accuracies of the technique remain to be
      determined.

PMID- 9560767
TI  - Juvenile-onset distal myopathy in Rottweiler dogs.
AB  - Two juvenile Rottweiler siblings were presented with the complaint of decreased
      activity and various postural abnormalities, including plantigrade and palmigrade
      stance and splayed forepaw digits. The neurologic examinations were otherwise
      normal. Electromyography revealed rare fibrillation potentials and positive sharp
      waves. Motor nerve conduction velocities were normal, whereas compound muscle
      action potentials from the interosseous muscles were decreased. These findings
      were consistent with a primary myopathy. A 3rd pup from a different litter and a
      4th pup from a litter with 3 of 8 affected dogs had similar clinical
      presentations. Histopathologic changes in fresh-frozen muscle biopsy samples were
      similar in all pups and consisted of myofiber atrophy with mild myonecrosis,
      endomysial fibrosis and replacement of muscle with fatty tissue. These changes
      were more severe in distal muscles than in proximal muscles. Plasma carnitine
      concentrations (total and free) were decreased in all pups. Muscle carnitine
      concentrations (total and free) were decreased in 3 of 4 pups and the least
      affected pup had a borderline low free muscle carnitine concentration.
      Abnormalities involving major metabolic pathways were not found on quantification
      of organic and amino acids. Dystrophin immunocytochemistry was normal in 2 dogs
      tested. Distal myopathies in humans are classified under the dystrophic group of
      muscle disorders. These 4 cases represent a form of muscular dystrophy apparently
      not previously reported in dogs.

PMID- 9560768
TI  - Left atrial paraganglioma in a dog: echocardiography, surgery, and scintigraphy.

PMID- 9560769
TI  - Congenital myotonia in 2 domestic cats.

PMID- 9560770
TI  - Possible adult onset myotonic dystrophy in a boxer.

PMID- 9560771
TI  - Diazepam used to control cluster seizures in dogs.

PMID- 9560772
TI  - Effects of thyroidectomy or thiouracil treatment on copulatory behavior in adult
      male rats.
AB  - Male copulatory behavior and the function of the hypothalamo-hypophysial-gonadal
      axis in hypothyroid male rats were investigated in the present study.
      Hypothyroidism was induced by thyroidectomy or thiouracil. In male copulatory
      behavior test, intromission latencies in hypothyroid rats were significantly
      longer than those in euthyroid rats and ejaculation frequencies were reduced in
      hypothyroid male rats compared to control rats without reduction of plasma
      concentrations of testosterone. These changes in copulatory behavior in
      hypothyroid male rats were restored to control levels by administration of T4 (5
      micrograms/rat). Hypothyroidism decreased adrenal weights, and basal and peak
      concentrations of corticosterone during diurnal variation, whereas it increased
      peak concentrations of ACTH in adult male rats. These results indicate that
      hypothyroidism causes adrenal dysfunction directly and results in hypersecretion
      of ACTH. The adrenal disturbance observed in hypothyroid rats may affect male
      copulatory behavior.

PMID- 9560773
TI  - Distribution of uropathogenic virulence factors among Escherichia coli strains
      isolated from dogs and cats.
AB  - A variety of virulence factors (VFs) such as type 1 fimbriae, pilus associated
      with pyelonephritis, S fimbriae, afimbrial adhesin, alpha-hemolysin, aerobactin
      and cytotoxic necrotizing factor 1 are associated with uropathogenic Escherichia
      coli. In this study, 80 uropathogenic E. coli strains in 50 dogs and 30 cats
      suffering from UTI. In addition, 60 E. coli strains were isolated from fecal
      samples from 30 each of healthy dogs and cats. The distribution of VFs of
      uropathogenic E. coli strains isolated from dogs and cats suffering from urinary
      tract infections (UTI) were examined by the colony hybridization test with seven
      DNA probes specific for VFs, and the results were compared with those obtained in
      the studies on strains from humans with UTI. In uropathogenic E. coli strains
      isolated from dogs and cats suffering from UTI, VFs were detected as frequently
      as in the strains isolated from humans with UTI. Although less frequently, genes
      encoding these VFs especially pap, sfa, hly, and cnf 1 genes were also associated
      with E. coli strains isolated from feces of healthy cats, in contrast to the
      distribution pattern of uropathogenic E. coli observed in humans. Furthermore,
      all VFs except pil were significantly more frequently detected in strains
      isolated from urine of animals with cystitis than in those isolated from feces of
      healthy humans. These results indicate that VFs of E. coli contribute to the
      pathogenesis of UTI in dogs and cats.

PMID- 9560774
TI  - A monoclonal antibody against dolphin lymphocytes (6E9) which recognizes bovine
      MHC class II antigens.
AB  - A monoclonal antibody, 6E9 established from mice injected with dolphin peripheral
      blood lymphocytes (PBLs) was characterized. In addition to its reactivity against
      89.4% of dolphin PBLs, 6E9 reacted with 33.1% of bovine PBLs of which 22% were
      CD5+, 11.1% were CD5-. 6E9 recognized a 34 kD protein on the surface of dolphin
      and bovine PBLs. Analysis of the protein's N-terminal amino acid sequence
      indicated that 6E9 recognizes bovine major histocompatibility complex (MHC) class
      II antigens. These results suggested that 6E9 recognized MHC class II antigens on
      bovine PBLs. As we have already produced an anti-dolphin MHC class I monoclonal
      antibody, analysis of immune system using these monoclonal antibodies will
      advance our understanding of the evolution of the mammalian immune system.

PMID- 9560775
TI  - Experimental dual infection of cesarean-derived, colostrum-deprived pigs with
      Mycoplasma hyopneumoniae and pseudorabies virus.
AB  - To determine whether pseudorabies virus (PRV) infection increases the severity of
      pneumonia by Mycoplasma hyopneumoniae, 18, 10-week-old Cesarean-derived,
      colostrum-deprived pigs were randomly assigned to 3 groups of 6 pigs each. Pigs
      in groups A and C were inoculated intranasally with M. hyopneumoniae at 10-week
      old. At 11-week-old, pigs in groups B and C were inoculated intranasally with
      PRV. All pigs were initially seronegative for M. hyopneumoniae and PRV. Three
      pigs of each group were euthanized at 12-week-old, and remaining pigs at 14-week
      old. At necropsy, gross lesions in the lung were observed in the pigs of groups A
      and C. On post-inoculation-week (PIW) 2 with M. hyopneumoniae (at 12-week-old),
      lung lesions were recognized in one of the 3 pigs in group A and all the pigs in
      group C. The mean percentage of the lung lesions were 0.1% in group A and 9.8% in
      group C. M. hyopneumoniae was isolated from broncho-alveolar lavage fluids (BALF)
      of pigs in group A with titer of 10(2) to 10(3) CCU/0.2 ml and in group C with
      titer of 10(5) to 10(6) CCU/0.2 ml. On PIW 4 (at 14-week-old), lung lesions were
      observed in all the pigs in groups A and C, and the mean percentage of the lung
      lesions were 8.3% in group A and 17.2% in group C. M. hyopneumoniae was isolated
      from BALF in group A with titer of 10(4) to 10(7) CCU/0.2 ml and in group C with
      titer of 10(6) to 10(7) CCU/0.2 ml. PRVs were isolated from nasal swab and tissue
      samples in groups B and C. After inoculation, antibody against M. hyopneumoniae
      was detected in groups A and C, and against PRV in groups B and C. Under the
      present experimental conditions, PRV infection appear to have effect on the
      severity of experimentally induced acute mycoplasmal pneumonia in young pigs.

PMID- 9560777
TI  - Sarcocystis suihominis detected for the first time from pigs in Japan.
AB  - Sarcoystis suihominis was detected for the first time in Japan from the heart and
      diaphragm of 5 out 600 older culled breeding pigs slaughtered in Saitama
      Prefecture, Japan. Fresh cysts were 1,080-2,040 x 106-170 microns in size.
      Bradysoites measured 15 x 4 microns on average. The cyst wall was usually
      observed thick, 4-6 microns, and striated, but occasionally thin and smooth
      according to the difference in sectioning angle and in portion of cysts. Scanning
      electron microscopy showed that many palisade-like villar protrusions, 6-6 x 0.3
      0.5 microns in size, were closely folded onto the surface of cyst. A small number
      of microtubules were seen in the core of protrusion. No dogs nor domestic cats
      fed with 20 fresh cysts each excreted oocysts or sporocysts in the feces
      throughout the experimental period of 30 days.

PMID- 9560776
TI  - Pasteurella multocida toxin and Bordetella bronchiseptica dermonecrotizing toxin
      elicit similar effects on cultured cells by different mechanisms.
AB  - We compared the effects of Pasteurella multocida toxin (PMT) with Bordetella
      bronchiseptica dermonecrotizing toxin (DNT) at a cellular level under same
      conditions. Both PMT and DNT cause actin stress fiber formation in MC3T3-E1 cells
      which is known to be regulated by the small GTP-binding protein Rho. DNT induced
      mobility shifts of Rho on SDS-polyacrylamide gel electrophoresis, indicating
      direct modification as reported elsewhere. In contrast, no alternations in the
      electrophoretic mobility of Rho were found in lysates from PMT-treated cells. PMT
      but not DNT increased the intracellular level of inositol phosphates, indicating
      the elevation of phospholipase C (PLC) activity in the PMT-treated cells. These
      results indicate that PMT does not have Rho as a target but activates PLC. The
      formation of actin stress fiber by PMT seems to be stimulated through the
      indirect activation of Rho, which resides downstream of PLC, PMT and DNT seem to
      elicit similar toxic effects, at least in part, through the activation of Rho.

PMID- 9560778
TI  - Prevalence of Listeria species in raw milk from farm bulk tanks in Nagano
      prefecture.
AB  - Raw milk samples from bulk tanks of a total of 943 farms, which corresponded to
      approximately 60% of all dairy farms in Nagano Prefecture were examined for
      Listeria species between December 1990 and April 1991. Listeria spp. were
      isolated from 29 (3.1%) of 943 milk specimens. In the southern, central, eastern
      and northern areas of the prefecture, Listeria spp. were isolated from 6.1%
      (22/362), 1.5% (4/272), 1.4% (2/143) and 0.6% (1/166) of samples, respectively.
      Listeria monocytogenes was isolated from three (0.3%) bulk tanks in the southern
      area: two of the strains isolated from two different farm bulk tanks were serovar
      4b, and the other one was 1/2a. Besides, between February 1991 and January 1992,
      504 samples of raw milk from farm bulk tanks were collected nine times from 56
      farms in the southern area, where the prevalence of Listeria spp. was the
      highest, and examined for the seasonal variation in the presence of Listeria spp.
      The prevalence of Listeria spp. was higher in spring (14.3%) than in autumn
      (4.8%). The 56 farms were divided into three groups according to the prevalence
      of Listeria spp., namely, three farms in Group 1 gave a high contamination rate
      (50% < or =), 14 farms in Group 2 a low contamination rate and the remaining 39
      farms in Group 3 no recovering of Listeria spp. Sixteen strains of L.
      monocytogenes serovar 4b were isolated from four farms.

PMID- 9560779
TI  - Eight-year observation and comparative study of specific pathogen-free cats
      experimentally infected with feline immunodeficiency virus (FIV) subtypes A and
      B: terminal acquired immunodeficiency syndrome in a cat infected with FIV
      petaluma strain.
AB  - Three specific pathogen-free cats experimentally infected with feline
      immunodeficiency virus (FIV) strains Petaluma, TM1 and TM2, respectively were
      observed for over 8 years. Without showing any significant clinical signs of
      immunodeficiency syndrome (AIDS) for 8 years and 4 months of asymptomatic phase,
      the Petaluma-infected cat exhibited severe stomatitis/gingivitis, anorexia,
      emaciation, hematological and immunological disorders such as severe anemia,
      lymphopenia, thrombocytopenia, and decrease of CD4/CD8 ratio to 0.075, and
      finally died with hemoperitoneum at 8 years and 8 months post-infection.
      Histopathological studies revealed that the cat had systemic lymphoid atrophy and
      bone marrow disorders indicating acute myelocytic leukemia (aleukemic type).
      Plasma viral titer of the cat at AIDS phase was considerably high and anti-FIV
      antibody titer was slightly low as compared with the other FIV-infected cats. In
      addition, immunoblotting analysis using serially collected serum/plasma samples
      of these cats revealed that antibodies against FIV proteins were induced in all
      the infected cats, however in the Petaluma-infected cat anti-Gag antibodies
      disappeared during the asymptomatic period. These results suggested that plasma
      viral load and anti-FIV Gag antibody response correlated with disease
      progression, and supported FIV-infected cats as a suitable animal model of human
      AIDS.

PMID- 9560780
TI  - A histometrical study on the long bones of raccoon dogs, Nyctereutes procyonoides
      and badgers, Meles meles.
AB  - To obtain the data required for identification of skeletal remains excavated from
      archaeological sites, histometrical observations were made in the cross sections
      of the mid-shaft of humerus, radius, femur and tibia of raccoon dogs (Nyctereutes
      procyonoides) and badgers (Meles meles) captured in Kagoshima Prefecture. There
      were interspecific differences between both animals in the breadth, the depth and
      the area of medullary cavity at the mid-shaft of the bones, all measurements were
      greater in male than in female bones. The thickness and the area of compact bones
      in male raccoon dogs were larger than those of female. No differences in
      histological structure could be detected among the bones, but an interspecific
      difference was found in the shape of osteons; round and constant-sized osteons
      consisting of 3 to 5 lamellae in raccoon dogs, while round or elliptic osteons
      varying in size from 3 to 8 lamellae in badgers. The ratios, the osteon areas per
      unit compact bone areas, were higher in all the bones of raccoon dogs. The short
      diameters of osteons and the ratios were greater in males in both animals. In
      females, the short diameter of osteons was smaller, and the number of osteons was
      larger. The results revealed interspecific differences between both animals and
      sexual dimorphism in each species.

PMID- 9560781
TI  - Evaluation of single-injection method of inulin and creatinine as a renal
      function test in normal cats.
AB  - A single injection method for estimating glomerular filtration rate (GFR) by
      measuring plasma inulin and creatinine clearances was evaluated in 10 healthy
      cats. GFRs were estimated from the plasma clearance (PC) by dividing the injected
      dose of an indicator by the area under the plasma disappearance curve (AUC). AUC
      was determined by 2 common pharmacokinetic analyses, the two-compartment model
      and the trapezoidal rule. AUCs determined by these two methods were significantly
      correlated both in inulin (r = 0.993) and creatinine (r = 0.959). To minimize
      errors, GFR was estimated by PC only if AUC/10 was greater than the area under
      the curve from the final sampling time to infinitive (A2). GFRs determined by PC
      of inulin at final sampling time of 180 and 240 min were 3.61 +/- 0.64 and 3.63
      +/- 0.67 ml/min/kg of body weight (mean +/- SD), respectively. These values
      corresponded to the reference range reported for normal cats. In contrast, when
      creatinine was used as a maker, A2 was always greater than AUC/10 at any final
      sampling time and GFRs estimated using these AUCs of creatinine were
      significantly greater than those of inulin, suggesting creatinine may not be
      suitable indicator for the single injection method.

PMID- 9560782
TI  - Pulmonary venous flow in normal dogs recorded by transthoracic echocardiography:
      techniques, anatomic validations and flow characteristics.
AB  - To observe pulmonary venous flow in dogs, the echocardiographic imaging planes
      and the techniques for examination, and the validations of anatomic location were
      investigated. Then, the velocity pattern of pulmonary venous flow was recorded in
      normal conscious dogs. Six imaging planes were available for observing the right
      or left caudal lobe pulmonary venous flow with two-dimensional or pulsed Doppler
      echocardiography. Of these, the left lateral apical 4-chamber view can be applied
      as standard view, because the pulmonary venous flow and transmitral flow could be
      recorded in this view simultaneously with small sampling angle. The velocity
      pattern of pulmonary venous flow demonstrated two forward waves in 19 of 20 dogs
      examined, with one peak occurring during ventricular systole and another during
      ventricular diastole. A reversed flow during atrial contraction was also seen in
      11 dogs. In the two forward waves, the mean peak velocity and velocity-time
      integral of ventricular diastolic forward flow were significantly higher than
      those of systolic forward flow (46.49 +/- 6.79 vs. 31.13 +/- 4.92 cm/s, p <
      0.0001 and 8.18 +/- 1.84 vs. 5.14 +/- 0.82 cm, p < 0.0001, respectively). The
      deceleration time of diastolic forward flow shortened with the increase of heart
      rate (r = -0.87, p < 0.0001). Pulmonary venous flow in dogs can be observed under
      transthoracic two-dimensional or pulsed Doppler echocardiography.

PMID- 9560783
TI  - Distribution of attenuated goose parvoviruses in Muscovy ducklings.
AB  - With a polymerase chain reaction (PCR) method, goose parvovirus (GPV) DNA was
      detected in Muscovy ducklings inoculated with attenuated GPV strains, IH and IHC.
      Strain IH that had been passed 20 times in Muscovy duck embryos could be detected
      in ducklings at 2- to 28-days after oral inoculation by PCR, however, a cell
      culture adapted strain IHC that had been passed 15 times in Muscovy duck embryos
      and then successively 50 times in Muscovy duck embryo fibroblasts could not be
      detected by 6 days postinoculation by the oral route, but via intramuscular
      inoculation the virus was detected from 6 dpi. With both strains Muscovy
      ducklings produced neutralizing antibodies against GPV, but GPV could be
      recovered from heart muscles even in birds that had high titer of neutralizing
      antibody. This means that GPV remains in birds for a long period under the
      presence of high titer of neutralizing antibody in the serum. Recovery of the
      virus was consistent with PCR results with one exception in which the bird had a
      neutralizing antibody titer of more than 100,000. After inoculation of these
      strains, no clinical signs were detected in ducklings. These results suggest that
      strains IH and IHC can be candidates for live attenuated vaccine for GPV
      infection.

PMID- 9560784
TI  - Monoclonal antibody TSd-1 is specific to elongating and matured spermatids in
      testis of common tree shrew (Tupaia glis).
AB  - The monoclonal antibody (MAb), named TSd-1, specific to spermatogenic cells of
      the common tree shrew (Tupaia glis) was established and characterized using
      immunohistochemistry and immunoblotting. MAb TSd-1 reacted with elongating and
      matured spermatids in a stage-dependent manner. TSd-1 recognized a 94 kilodalton
      (kDa) peptide in the plasma membrane and cytosol. Additionally, an extremely weak
      107 kDa band was detected only in the cytosol. The reactions were not detected in
      round spermatids. In elongating Stage VI spermatids, the plasma membrane and the
      granular structure within the cytoplasm were intensely positive, and most intense
      after the appearance of new round spermatids in the lower layer (Stage I). The
      reactions were observed neither in the other organs of the common tree shrew nor
      in the testes of other animals, indicating that TSd-1 antigen is specific to the
      spermatogenic cells of the common tree shrew, and may act on elongating or
      matured spermatids.

PMID- 9560785
TI  - Localization of metallothionein-I and -II in hypertrophic astrocytes in brain
      lesions of dogs.
AB  - To study the neurophysiological functions of metallothioneins (MTs), localization
      of MT-I and -II was examined immunohistochemically in a variety of brain lesions
      in dogs, including infarct, laminar cortical necrosis, hemorrhage, invasive
      growth of tumour, inflammatory lesions in granulomatous meningoencephalitis and
      distemper encephalitis. MT-I and -II were demonstrated in both nucleus and
      cytoplasm of hypertrophic astrocytes in most brain lesions examined regardless of
      the type, size, localization and duration of the lesions. In addition, MT
      expression was stronger in a population of hypertrophic astrocytes localizing
      inside of the surviving brain tissue rather than those localizing at the boundary
      between the surviving brain tissue and necrotic area, where severe inflammatory
      changes were developing. These results suggest that MT-I and -II may play roles
      not only in protection of neurons from metals and free radicals ubiquitous in the
      inflammatory lesions but also in repair of injured neural tissues.

PMID- 9560786
TI  - Effects of the deleted form of hepatocyte growth factor on serum hyaluronate
      levels in rats with liver cirrhosis.
AB  - Effects of the deleted form of hepatocyte growth factor (dHGF) on serum
      hyaluronate levels, an index for liver cirrhosis, were studied in rats. The
      levels of serum hyaluronate increased in rats with dimethylnitrosamine- or
      carbontetrachloride-induced cirrhotic liver with prolongation of prothrombin
      time, which indicates disorder of liver function. Daily intravenous injection of
      dHGF reduced the elevated serum hyaluronate levels with improvement of the
      prolonged prothrombin time. These results suggest that the amelioration of
      hepatic function disorder by dHGF leads to a reduction of the increased serum
      hyaluronate levels.

PMID- 9560787
TI  - Rapid and progressive CD4+ decline in a monkey infected with an SIV+HIV-1
      chimeric virus.
AB  - We previously constructed a simian immunodeficiency virus+human immunodeficiency
      virus type 1 (HIV-1) chimeric virus, NM-3rN to generate a pathogenic HIV-1 in
      macaque monkeys. During the in vivo passage of this virus in several monkeys, a
      viral strain, R43-56 was obtained which acquired a better replication ability in
      vivo. MM121, one of the three monkeys inoculated with the R43-56, showed weight
      loss, diarrhea and a rapid and continuous decrease in CD4+ lymphocytes at the
      moribund stage. An autopsy revealed generalized lymphadenopathy, dehydration, and
      ileocecal intussusception. In situ hybridization showed that the virus infection
      was in systemic lymphoid organs. We are presently monitoring the survivors to
      obtain candidates for a more virulent virus. R43-56 may be a better challenge
      virus and useful tool for human acquired immunodeficiency syndrome research.

PMID- 9560788
TI  - Effect of oxygen concentration in the gas atmosphere during in vitro insemination
      of bovine oocytes on the subsequent embryonic development in vitro.
AB  - In vitro matured bovine oocytes were co-incubated with sperm for 18 hr in a
      droplet of fertilization medium under a gas atmosphere of 5% CO2 with 5 or 20%
      O2. After removing the cumulus cells, they were fixed to examine their
      fertilization rate, or cultured for another 154 hr in a chemically defined medium
      under 5% O2 to determine their development to the blastocyst stage. There was no
      difference between the 5 and 20% O2 groups in the fertilization rate. However,
      the percentage of inseminated oocytes which developed to the blastocyst stage was
      higher when in vitro insemination was conducted under 5% O2 compared with that
      under 20% O2 (34.4 vs. 24.7%, P < 0.05).

PMID- 9560789
TI  - Growth inhibitory effect of bovine lactoferrin to Toxoplasma gondii tachyzoites
      in murine macrophages: tyrosine phosphorylation in murine macrophages induced by
      bovine lactoferrin.
AB  - Previous studies have shown that lactoferrin induces growth inhibitory effects in
      mouse macrophages against intracellular Toxoplasma gondii, and these effects were
      not mediated by the oxygen-dependent and inorganic nitrogen-dependent pathway. To
      clarify the mechanism of anti-Toxoplasma gondii activity induced by lactoferrin,
      we examined whether lactoferrin promoted the phosphorylation of tyrosine residues
      in macrophage proteins. In immunoblotting assays using anti-[phosphorylated
      tyrosine] monoclonal antibody, phosphorylation of tyrosine residues was detected
      in protein(s) of approximately 30 kDa in macrophages incubated with lactoferrin.
      Inhibition of the lactoferrin-induced tyrosine-phosphorylation by genistein led
      to loss of the lactoferrin-induced growth inhibitory effect against the
      parasites. These findings suggest that lactoferrin induces tyrosine
      phosphorylation in macrophages, and the tyrosine-phosphorylation seems to be
      associated with the induction of the growth inhibitory activity exerted against
      intracellular Toxoplasma gondii.

PMID- 9560790
TI  - X-linked locus is responsible for non-insulin-dependent diabetes mellitus in the
      OLETF rat.
AB  - The Otsuka Long-Evans Tokushima Fatty (OLETF) rat has been recently established
      as the best model of non-insulin-dependent diabetes mellitus (NIDDM) with mild
      obesity. In this study, we found that the F1 progeny produced from the crosses of
      OLETF and F344 rats exhibit a reciprocal cross effect on NIDDM-relevant
      phenotypes, fasting and postprandial glucose levels and body weight, suggesting
      the existence of X-linked locus affecting susceptibility to NIDDM. We thus
      examined the linkage between 7 X-linked microsatellite markers and NIDDM-relevant
      phenotypes, using 160 (OLETF x F344)F2 progeny. Suggestive evidence for a X
      linked locus affecting glucose levels at 120 min after glucose administration was
      found in a region near X-linked marker, DXMgh4. The identified locus also showed
      significant effects on fasting glucose levels and body weight.

PMID- 9560791
TI  - Increased ductal responsiveness to PGE2 after maternal treatment with aspirin and
      ibuprofen.
AB  - This work was conducted to determine whether aspirin and ibuprofen, when
      administered prenatally may potentiate a reopening of the neonatal ductus
      arteriosus (DA) induced by PGE2 after postnatal closure. In the first experiment,
      a subcutaneous injection of PGE2 (4 microgram(s)) was administered to newborn
      rats 3 hr after a Cesarean delivery from pregnant females which had been orally
      given 100 or 300 mg/kg/day of aspirin and 10 or 30 mg/kg/day of ibuprofen on days
      18, 19 and 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was
      determined at intervals after the injection. The DA/PA ratio was significantly
      higher in newborn rats from mothers who were transplacentally administered these
      agents than the control. We also examined the hypothesis that maternal treatment
      with nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen,
      inhibits the catabolism of PGE2 and that the increased reopening of the DA was
      partly due to this inhibition. 15-hydroxy prostaglandin dehydrogenase (15-PGDH)
      in neonatal lungs, the key enzyme involved in catalyzing PGE2 to convert it to
      its inactive metabolite 15-keto-PGE2, was not affected by maternal treatment with
      aspirin and ibuprofen. These results suggest that the increased ductal
      responsiveness to PGE2 in newborn rats was a common response after maternal NSAID
      treatment, but the catabolism of PGE2 in the lungs did not always contribute to
      this response.

PMID- 9560792
TI  - The nucleotide and predicted amino acid sequence of the fusion protein of recent
      isolates of canine distemper virus in Japan.
AB  - Analysis of the molecular properties of fusion (F) proteins of field isolates of
      canine distemper virus (CDV) by immunoprecipitation analysis revealed an
      identical molecular mass of F protein of 3 field isolates as well as the
      Onderstepoort laboratory strain. Sequencing showed that the F gene of a field
      isolate (the Yanaka strain) shared 90.1% and 95.7% identities with the
      Onderstepoort strain at nucleotide and amino acid levels, respectively. All of
      the 13 cysteine residues and 4 potential asparagine-linked glycosylation sites
      were completely conserved amongst these strains. These results indicate that the
      F proteins is much less heterogeneous than that observed in the hemagglutinin
      proteins of CDV.

PMID- 9560793
TI  - C-cell adenoma containing variously sized thyroid follicles in a horse.
AB  - A thyroid gland tumor, showing unusual histology, was identified in a 13-year-old
      male Andalusian horse. Microscopically, the tumor consisted of neoplastic
      proliferation of C-cell (parafollicular cell) with cytoplasmic fine granules,
      containing diffusely distributed, variously sized colloid-containing follicles.
      Immunohistochemically, the neoplastic C-cell were positive for calcitonin and
      follicleforming epithelial cells showed a positive reaction for thyroglobulin.
      Ultrastructurally, membrane-bound secretory granules up to 250 nm in diameter
      were found in the cytoplasm of the parafollicular cells, whereas the follicular
      epithelial cells had microvilli, junctional complex, and well-developed
      endoplasmic reticulum.

PMID- 9560794
TI  - Histological changes in the endometrial arterioles during postpartum offthe
      Chinese hamster (Cricetulus griceus).
AB  - The morphology of the uterine wall in the postpartum Chinese hamster (Cricetulus
      griceus) was studied with particular reference to the changes in the arterioles
      in the mesometrial endometrium. At day 0 postpartum, the endometrial arterioles
      were characterized by the appearance of trophoblastic giant cells plugging
      ruptured arterioles. On days 1 to 3 postpartum, the giant cells were replaced by
      epitheloid cells. On days 4 to 5 postpartum, the epitheloid cell mass was invaded
      by fibroblasts to occlude the arterial lumens. On days 6 to 7 postpartum,
      endometrial regeneration was completed. The giant cell might play a role in
      hemostasis immediately after parturition.

PMID- 9560795
TI  - Rearrangement of c-myc gene in rapidly induced avian lymphoid leukosis tumors.
AB  - Southern blot hybridization of DNA samples from 9 primary tumors of avian
      lymphoid leukosis (LL) rapidly induced by ALV infection 27-74 days post
      inoculation was carried out to search for rearrangement of the c-myc gene with
      human c-myc gene exon III as a probe. Rearrangement of the c-myc gene was
      detected by appearance of new EcoRI fragments in 7 out of 9 tumors examined. The
      size of the fragments ranged from 3.1 to 4.0 kilobases (kb). In addition to these
      fragments, two fragments (9.0 kb and 13 kb) were observed in one tumor, and a
      faint fragment (3.5 kb) was observed in another tumor. Rearrangement of the c-myc
      gene was not detected in the remaining two tumors kept in unsuitable condition.
      These results suggest that rearrangement of c-myc gene was induced even in
      rapidly induced LL as well as that induced after long incubation period. This is
      the first report of involvement of c-myc gene in rapidly induced B-cell lymphoma
      (LL).

PMID- 9560796
TI  - Prevalence of antibodies of field pseudorabies virus in pigs of herd vaccinated
      with live vaccine.
AB  - This trial was performed in a 350-sow farrow-to-finish pig farm in which animals
      had been vaccinated against Aujeszky's disease with glycoprotein gC deletion (gC(
      )) vaccine. The prevalence of antibodies against field pseudorabies virus (PRV)
      in serum samples collected from sows and fattening pigs during the period March
      1995 to May 1997 was determined by using a commercial assay kit. The frequencies
      with which PRV-positive sows were found were 28.9% and 25.0% in March and October
      of 1995, 12.5% and 2.5% in April and October of 1996, and 0% in May of 1997. The
      fattening pigs tested at these times had no antibody to field PRV. These results
      thus indicate the probability that the PRV infection at the farm was eliminated
      by the gC(-) vaccine.

PMID- 9560797
TI  - Dietary methionine level affects linoleic acid metabolism through
      phosphatidylethanolamine N-methylation in rats.
AB  - The effects of dietary methionine level on the profiles of fatty acids and
      phospholipids and on the plasma cholesterol concentration were investigated to
      confirm whether the methionine content of dietary proteins is one of the major
      factors that cause differential effects on lipid metabolism. The effect of
      dietary supplementation with eritadenine, which is shown to be a potent inhibitor
      of phosphatidylethanolamine (PE) N-methylation, was also investigated. Rats were
      fed six diets containing casein (100 g/kg) and amino acid mixture (86.4 g/kg)
      differing in methionine content (2.5, 4.5, and 7.5 g/kg) and without or with
      eritadenine supplementation (30 mg/kg) for 14 d. The ratio of arachidonic to
      linoleic acid of liver microsomal and plasma phosphatidylcholine (PC) was
      significantly increased as the methionine level of diet was elevated, indicating
      that dietary methionine stimulates the metabolism of linoleic acid. The PC/PE
      ratio of liver microsomes and the plasma cholesterol concentration were also
      increased by dietary methionine. These effects of methionine were completely
      abolished by eritadenine supplementation The S-adenosylmethionine concentration
      in the liver reflected the methionine level of diet. These results support the
      idea that the differential effects of dietary proteins on lipid metabolism might
      be ascribed, at least in part, to their different methionine contents, and that
      methionine might exert its effects through alteration of PE N-methylation.

PMID- 9560798
TI  - Interaction of n-3 long-chain polyunsaturated fatty acids with n-6 fatty acids in
      suckled rat pups.
AB  - The addition of long-chain polyunsaturated fatty acids (LCP: C20, and C22) to
      infant formula may permit fatty acid accretion rates similar to breast-fed
      infants, and may have long-term outcome benefits, such as improved visual acuity
      and cognitive development. Although fish oil may provide a source of n-3 LCP,
      sources of n-6 LCP have been more difficult to identify. The present study
      evaluates the effects of n-3 and n-6 LCP derived from single-cell oils on liver,
      plasma, and brain fatty acid levels in a neonatal animal model. Newborn rat pups
      were suckled for 14 d by dams receiving diets containing n-3 LCP alone or
      combinations of n-3 LCP and increasing doses of linoleic acid (18:2n-6) or
      arachidonic acid (20:4n-6). Dietary groups received 2% n-3 LCP and 1, 2, or 5% of
      either 18:2n-6 or 20:4n-6. The 20:4n-6 source also contained modest levels of
      18:2n-6. At the termination of the study, liver, plasma, and brain were obtained
      from the rat pups and the phospholipid fatty acid profiles determined. The
      results indicate complex interactions of n-3 and n-6 fatty acids. Groups
      receiving dietary 20:4n-6 incorporated higher levels of n-6 LCP into tissues than
      did the groups receiving 18:2n-6. The brain was relatively resistant to changes
      in fatty acid composition compared with the liver and plasma. As expected, tissue
      n-3 LCP levels were reciprocally related to n-6 levels. The present results
      document that single-cell LCP oils are bioavailable in a neonatal animal model.
      The use of 20:4n-6 is a more effective means of supporting n-6 status than the
      use of 18:2n-6. These results may have implications for the addition of LCP to
      infant formula.

PMID- 9560799
TI  - Diabetes-induced and age-related changes in fatty acid proportions of plasma
      lipids in rats.
AB  - Diabetes-induced and age-related proportional changes in plasma fatty acids of
      triglycerides (TG), phospholipids (PL), and cholesteryl esters (CE) were
      investigated using streptozotocin-induced diabetic and control rats. Among n-6
      fatty acids from diabetic rat plasma, increased proportions of 18:2n-6 and 20:3n
      6 in all three lipid classes and of 18:3n-6 in PL at 1-3 months old and in TG at
      3-5 months old were observed. The proportions of 20:4n-6 decreased in both PL and
      CE, but were unchanged in diabetic TG. Among the n-3 fatty acids, in the early
      stage, diabetes caused increases in the proportions of 18:3n-3 in PL and CE and
      of 20:5n-3 and 22:6n-3 in TG, while 22:5n-3 was decreased later in the disease
      course. These results suggest reduced delta 5-desaturase activities on 20:3n-6
      but not on 20:4n-3, while delta 6-desaturase activity on 18:2n-6 was essentially
      unaffected. Furthermore, the reduction in delta 9-desaturase activity in diabetic
      rats may well explain the decreases in the proportions of 16:1n-7 and 18:1n-7.
      However, the proportion of 18:1n-9, another product of delta 9-desaturase, was
      significantly increased in CE and PL as compared to the controls. Thus, there was
      a discrepancy between our results and those of earlier studies with respect to
      the n-9, n-6, and n-3 fatty acid proportions of plasma lipids in diabetic rats.
      We also investigated age-related changes in the proportions of plasma fatty
      acids. Although rather small, age-related changes were evident in both diabetic
      and control rats.

PMID- 9560800
TI  - Effect of continuous enteral medium-chain fatty acid infusion on lipid metabolism
      in rats.
AB  - This study compared (i) the relative effects of long-chain triglycerides (LCT)
      and medium-chain triglycerides (MCT), (ii) the influence of amount of MCT, and
      (iii) the impact of medium-chain fatty acid position, on plasma and lymphatic
      triglycerides and portal vein free fatty acids. The animals were fed
      approximately at 250 kcal/kg.day for 20 h. The lymph from lymphatic duct and
      blood from portal vein and systemic circulation were collected. The results
      showed that feeding 100% MCT for 20 h was sufficiently long to reduce
      significantly the level of linoleic acid in portal vein fatty acids and plasma
      and lymph triglycerides. However, this alteration induced by MCT feeding was
      partially prevented by adding LCT to the diet. The level of arachidonic acid was
      significantly reduced in plasma triglycerides by any of the diets containing
      medium-chain fatty acids compared to 100% LCT. When feeding MCT only, palmitoleic
      acid, presumably reflecting de novo lipogenesis, was increased in lymphatic
      triglycerides and portal vein fatty acids. Total saturated fatty acids as a total
      percentage of total fatty acids were also significantly increased in plasma and
      lymphatic triglycerides and portal vein fatty acids. Thus, when linoleic acid is
      limiting, the conversion of MCT into long-chain fatty acids by de novo
      lipogenesis is likely to be an important metabolic route. Providing LCT with MCT
      or 2-monodecanoin appears to limit this pathway.

PMID- 9560801
TI  - Absorption, excretion, and distribution of plant sterols after proximal gut
      resection and autotransplantation of porcine ileum.
AB  - Contribution of different gut segments to plant sterol absorption, adaptation of
      plant sterol absorption after partial small bowel resection, and effects of gut
      transplantation (necessitates extrinsic autonomic denervation and lymphatic
      disruption) on plant sterol biodynamics are unclear. We studied the consequences
      of massive proximal small bowel resection and autotransplantation of the
      remaining ileum on the adaptive absorption and biodynamics of plant sterols.
      Dietary, fecal, biliary, hepatic and plasma plant sterols, fecal elimination and
      absorption of cholesterol, small bowel morphology, and intestinal transit were
      determined before (n = 5) and at 4, 8, and 14 wk after resection of the proximal
      75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum (n
      = 15) or transection (n = 5). Proximal gut resection significantly reduced
      cholesterol absorption efficiency; percentage absorption and biliary secretion of
      plant sterols; plasma, biliary and hepatic campesterol-to-cholesterol
      proportions; and sitosterol proportions in plasma and bile. Autotransplantation
      of the remaining ileum further significantly decreased cholesterol absorption
      efficiency; percentage absorption and biliary secretion of campesterol;
      campesterol proportions in plasma, bile and liver; and plasma proportions of
      sitosterol while increasing fecal excretion of neutral and acidic steroids.
      Plasma proportions of the two plant sterols, but absorption of just campesterol,
      were gradually improved with increasing cholesterol absorption and villus height
      after proximal gut resection; the same result was observed to a lesser degree
      after ileal autotransplantation. In addition, significant positive correlations
      were found between percentage cholesterol and campesterol absorption and the
      plasma plant sterol proportions in both proximal resection groups, between
      campesterol absorption and ileal villus height in the resection group, and
      between campesterol absorption and intestinal transit time in the
      autotransplantation group. In conclusion, plasma campesterol and sitosterol
      closely reflect absorption of cholesterol and plant sterols from intact and
      autotransplanted ileum during adaptation to proximal gut resection. A loss of
      proximal gut absorptive surface impairs cholesterol and campesterol absorption
      more than sitosterol absorption, the latter being apparently less dependent on
      available jejunal villus surface area.

PMID- 9560802
TI  - The effect of dietary vitamin E supply and a moderately oxidized oil on
      activities of hepatic lipogenic enzymes in rats.
AB  - Diets rich in polyunsaturated fatty acids (PUFA) are well known to suppress
      hepatic lipogenic enzymes compared to fat-free diets or diets rich in saturated
      fatty acids. However, the mechanism underlying suppression of lipogenic enzymes
      is not quite clear. The present study was undertaken to investigate whether lipid
      peroxidation products are involved in suppression of lipogenic enzymes.
      Therefore, an experiment with growing male rats assigned to six groups over a
      period of 40 d was carried out. Rats received semisynthetic diets containing 9.5%
      coconut oil and 0.5% fresh soybean oil (coconut oil diet, peroxide value 5.1 meq
      O2/kg oil), 10% fresh soybean oil (fresh soybean oil diet, peroxide value 9.5 meq
      O2/kg oil), or 10% thermally treated soybean oil (oxidized soybean oil diet,
      peroxide value 74 meq O2/kg oil). To modify the antioxidant state of the rats, we
      varied the vitamin E supply (11 and 511 mg alpha-tocopherol equivalents per kg of
      diet) according to a bi-factorial design. Food intake and body weight gain were
      not influenced by dietary fat and vitamin E supply. Activities of hepatic
      lipogenic enzymes were markedly influenced by the dietary fat. Feeding either
      fresh or oxidized soybean oil diets markedly reduced activities of fatty acid
      synthase, (FAS), acetyl CoA-carboxylase, (AcCX), glucose-6-phosphate
      dehydrogenase, (G6PDH), 6-phosphogluconate dehydrogenase, and ATP citrate lyase
      (ACL) relative to feeding the coconut oil diet. Moreover, feeding oxidized
      soybean oil slightly, but significantly, lowered activities of FAS, AcCX, and ACL
      compared to feeding fresh soybean oil. Activities of hepatic lipogenic enzymes
      were reflected by concentrations of triglycerides in liver and plasma. Rats fed
      the coconut oil diet had markedly higher triglyceride concentrations in liver and
      plasma than rats consuming fresh or oxidized soybean oil diets, and rats fed
      oxidized soybean oil had lower concentrations than rats fed fresh soybean oil.
      The vitamin E supply of the rats markedly influenced concentrations of
      thiobarbituric acid-reactive substances in liver, but it did not influence
      activities of hepatic lipogenic enzymes. Because the vitamin E supply had no
      effect, and ingestion of an oxidized oil had only a minor effect, on activities
      of hepatic lipogenic enzymes, it is strongly suggested that neither exogenous nor
      endogenous lipid peroxidation products play a significant role in the suppression
      of hepatic lipogenic enzymes by diets rich in PUFA. Therefore, we assumed that
      dietary PUFA themselves are involved in regulation of hepatic lipogenic enzymes.
      Nevertheless, the study shows that ingestion of oxidized oils, regardless of the
      vitamin E supply, also affects hepatic lipogenesis, and hence influences
      triglyceride levels in liver and plasma.

PMID- 9560803
TI  - Effects of polyunsaturated fatty acids and their n-6 hydroperoxides on growth of
      five malignant cell lines and the significance of culture media.
AB  - We examined effects of polyunsaturated fatty acids (PUFA), their corresponding
      hydroperoxy fatty acids (hp-PUFA), as well as various pro- and antioxidants on
      the growth of tumor cells in culture. When cultured in RPMI 1640 medium, A-427
      and WEHI clone 13 cells were both highly sensitive to hydroperoxy docosahexaenoic
      acid (hp-DHA), but they were far less sensitive in minimum essential medium
      (MEM). In contrast, A-427 cells were also sensitive to DHA in both culture media,
      while WEHI clone 13 cells, as well as other cell lines, tested in their
      respective media, were resistant. The lower sensitivity of the cell lines to hp
      DHA in MEM-medium was apparently due to a more rapid reduction of hp-DHA to the
      corresponding hydroxy-DHA in MEM-medium. Addition of glutathione (GSH) to the
      culture medium abolished the effects of hp-DHA, but not the effects of DHA, while
      depletion of intracellular GSH levels by L-buthionine-S,R-sulfoximine strongly
      enhanced the cytotoxic effect of hp-DHA, but not the cytotoxic effect of DHA.
      alpha-Tocopherol protected A-427 cells against the toxic effect of DHA and
      abolished the induced lipid peroxidation, while it did not protect against the
      toxic effects of hp-DHA in A-427 or WEHI clone 13 cells. Ascorbic acid reduced
      the cytotoxic effect of DHA, but potentiated the toxic effect of hp-DHA while
      selenite essentially abolished the toxicity of both DHA and hp-DHA. These results
      indicate that sensitivity of tumor cell lines to PUFA and their oxidation
      products depends on their antioxidant defense mechanisms, as well as culture
      conditions, and establishes hp-DHA as a major, but probably not the sole,
      metabolite responsible for cytotoxicity of DHA.

PMID- 9560804
TI  - Cytotoxicity of tocopherols and their quinones in drug-sensitive and multidrug
      resistant leukemia cells.
AB  - Cytotoxicities of tocopherols (alpha-T, gamma-T, delta-t), their para (alpha-TQ,
      gamma-TQ, delta-TQ)- and ortho (Tocored)-quinone oxidation products, the
      synthetic quinone analog of gamma-TQ containing a methyl group substituted for
      the phytyl side-chain (TMCQ) and the synthetic quinone analog of Tocored
      containing a methyl group substituted for the phytyl side-chain (PR) were
      measured in acute lymphoblastic leukemia cell lines that are drug-sensitive (CEM)
      and multidrug-resistant (CEM/VLB100). Among tocopherols, only delta-T exhibited
      cytotoxicity. Among para quinones, alpha-TQ showed no cytotoxicity, while gamma
      TQ and delta-TQ were highly cytotoxic in both CEM and CEM/VLB100 cell lines (LD50
      < 10 muM). delta-TQ and gamma-TQ were more cytotoxic than the widely studied
      chemotherapeutic agent doxorubicin, which also showed selective cytotoxicity to
      CEM cells. The orthoquinone Tocored was less cytotoxic than doxorubicin in drug
      sensitive cells but more cytotoxic than doxorubicin in multidrug-resistant cells.
      Cytotoxicity was not a function of the phytyl side-chain since both TMCQ and PR
      were cytotoxic in leukemia cells. Cytotoxic para and ortho quinones were
      electrophiles that formed adducts with nucleophilic thiol groups in glutathione
      and 2-mercaptoethanol. Cytotoxicity was enhanced when the glutathione pool was
      depleted by preincubation with buthionine-[S,R]-sulfoximine, but cytotoxicity was
      diminished by the addition of N-acetylcysteine to cultures. alpha-T also
      diminished the cytotoxicity of para- and orthoquinones. Buthionine-[S,R]
      sulfoximine did not block the inhibitory effect of either N-acetylcysteine or
      alpha-T, showing that these agents did not act solely by maintaining the
      glutathione pool as an essential antioxidant system. In conclusion,
      tocopherylquinones represent a new class of alkylating electrophilic quinones
      that function as highly cytotoxic agents and escape multidrug resistance in acute
      lymphoblastic leukemia cell lines.

PMID- 9560805
TI  - Conversion of palmitate to unsaturated fatty acids differs in a Neurospora crassa
      mutant with impaired fatty acid synthase activity.
AB  - The Neurospora crassa cel (fatty acid chain elongation) mutant has impaired fatty
      acid synthase activity. The cel mutant requires exogenous 16:0 for growth and
      converts 16:0 to other fatty acids. In contrast to wild-type N. crassa, which
      converted only 42% of the exogenous [7,7,8,8-(2)H4]16:0 that was incorporated
      into cell lipids to unsaturated fatty acids, cel converted 72%. In addition, cel
      contains higher levels of 18:3(delta 9,12,15) than wild-type, and synthesizes two
      fatty acids, 20:2(delta 11,14 and 20:3(delta 11,14,17, found at only trace levels
      in wild-type. Thus, the delta 15-desaturase activity and elongation activity on
      18-carbon polyunsaturated fatty acids are higher for cel than wild-type. This
      altered metabolism of exogenous 16:0 may be directly due to impaired flux through
      the endogenous fatty acid biosynthetic pathway, or may result from altered
      regulation of the synthesis of unsaturated fatty acids in the mutant.

PMID- 9560806
TI  - Identification of ceramide-phosphorylethanolamine in oomycete plant pathogens:
      Pythium ultimum, Phytophthora infestans, and Phytophthora capsici.
AB  - Cellular lipids were extracted from three species of Oomycete plant pathogens
      (Pythium ultimum, Phytophthora infestans, and Ph. capsici) and analyzed via
      normal-phase high-performance liquid chromatography with flame-ionization
      detection. The most abundant polar lipids in each of the three species were the
      polar membrane lipids, phosphatidylethanolamine (PE), phosphatidylcholine, and a
      phosphosphingolipid that eluted soon after PE. Structural analysis via mass
      spectrometry and nuclear magnetic resonance spectrometry revealed that the
      phosphosphingolipid was ceramide phosphorylethanolamine (Cer-PE). The most
      abundant molecular species of Cer-PE in P. ultimum had a molecular weight of
      670.5, contained an unusual 19-carbon branched triunsaturated sphingoid (C19
      delta 4, 8, 10, 9-methyl long-chain base) and palmitic acid as the amide-linked
      fatty acid. The most abundant molecular species of Cer-PE in Ph. infestans had a
      molecular weight of 714.5, contained a common 16-carbon 1,3 di-OH sphingoid, and
      erucic (cis 13-docosenoic, C22-delta 13) acid as the amide-linked fatty acid. The
      Cer-PE in Ph. capsici comprised a mixture of each of the two molecular species
      found in P. ultimum and Ph. infestans.

PMID- 9560807
TI  - Lipids of Thermococcus hydrothermalis, an archaea isolated from a deep-sea
      hydrothermal vent.
AB  - The membrane lipids of a deep-sea hydrothermal vent archaea, Thermococcus
      hydrothermalis, were isolated, purified, and structurally characterized. On the
      basis of acid methanolysis and spectroscopic studies, the polar lipids, amounting
      to 4.5% (w/w) of the dry cells, comprised diphytanyl glycerol diethers and
      dibiphytanyldiglycerol tetraethers, in a 45:55 ratio. No cyclopentane ring was
      present in the tetraethers. From the neutral lipids, accounting for 0.4% (w/w) of
      the dry cells, besides low amounts of di- and tetraethers occurring in a free
      form, four acyclic tetraterpenoid hydrocarbons, di- and tri-unsaturated were
      identified. All were structurally related to lycopane. The presence of these
      hydrocarbons provides some evidence that lycopane, widely distributed in oceans,
      could be derived, at least partially, from the hydrocarbons synthesized by some
      thermophilic Archaea. Finally, analysis of the uninoculated culture medium
      indicates that fatty acid derivatives and some steroid and triterpenoid compounds
      identified in the lipidic extract of the archaea originated from the culture
      medium.

PMID- 9560808
TI  - Fatty acid composition of the cellular slime mold Polysphondylium pallidum.
AB  - The cellular slime mold Polysphondylium pallidum was grown upon Escherichia coli
      B/r, and the fatty acid compositions of total lipids obtained from vegetative
      amebae and aggregation-competent cells were compared. Fatty acids isolated from
      vegetative cells included C-17 and C-19 cyclopropane fatty acids and also
      straight-chain, saturated fatty acids. The cyclopropane fatty acids were derived
      from the ingested bacteria. Development of amebae to aggregation-competent cells
      was accompanied by a substantial decrease in saturated cyclopropane fatty acids
      and a concomitant increase in unsaturated fatty acids and unsaturated
      cyclopropane fatty acids, mostly as 18:3 (5,9,12). We report here the fatty acid
      composition and identify the occurrence of delta 5 desaturation of cyclopropane
      fatty acids, namely, 9,10-methylene 5-hexadecenoic acid and 11,12-methylene 5
      octadecenoic acid. These fatty acids have not been reported previously in the
      related species Dictyostelium discoideum, which also feeds on E. coli B/r and has
      delta 5-desaturation activity.

PMID- 9560810
TI  - [Choice of electron equipment for x-ray diagnostic digital scanning system].
AB  - The paper deals with the choice of electron equipment for X-ray diagnostic
      devices with digital image processing which are intended for population-based
      mass prophylactic examinations of lung. Guidelines for the optimization of the
      package of electron devices for processing and storing of data and for obtaining
      hard copies of X-ray films.

PMID- 9560811
TI  - [Methodology of obtaining and digital processing of adhesive cells].
AB  - The paper deals with the methodological features of investigations of the
      interaction of cells and foreign material surfaces by scanning electron
      microscopy. The proposed technique for obtaining electron microscopic images
      results in their easy binarization and further treatment using computer software.
      The specificity of obtaining electron microphotographs permits detailed
      quantitative image analysis. This approach enables one to study both quantity of
      objects and their individual morphologies, as well as to define distributions of
      objects by their diameter, area, etc. Human platelet adhesion to glass and metal
      is considered as an example.

PMID- 9560809
TI  - Rapid hydrolysis of bile acid conjugates using microwaves: retention of absolute
      stereochemistry in the hydrolysis of (25R) 3 alpha,7 alpha,12 alpha-trihydroxy-5
      beta-cholestan-26-oyltaurine.
AB  - In recent years, defects of bile acid synthesis caused by disorders of peroxisome
      biogenesis have led to increased interest in C27 bile acids. In humans, while the
      majority of bile acids are C24 carboxylic acids, the presence of increased
      concentrations of C27 bile acids and their metabolites in hereditary diseases
      associated with peroxisomal dysfunction can serve as a useful marker for the
      intensity of the metabolic disorder. Our present studies describe an efficient
      method for the rapid hydrolysis of C27 and C24 bile acid conjugates using a
      commercial microwave oven. The advantages of this method include freedom from
      racemization, minimal activation, mild reaction conditions, and the highly
      stereocontrolled nature of the reaction, thus allowing for free bile acid
      recovery in high yield. For example, when (25R) 3 alpha,7 alpha,12 alpha
      trihydroxy-5 beta-cholestan-26-oyl taurine, a major compound present in the bile
      of Alligator mississippiensis, was deconjugated with 4% NaOH/diethylene glycol or
      1 M LiOH/propylene glycol in the microwave oven for 4-6 min, 3 alpha,7 alpha,12
      alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA) was obtained in 81% yield
      with retention of configuration at C-25. It is suggested that present studies
      will be helpful in delineating the absolute stereochemistry of 3 alpha,7 alpha,12
      alpha-trihydroxy-5 beta-cholestanoyl-CoA oxidase, the peroxisomal enzyme that
      catalyzes the first step in the oxidation of THCA.

PMID- 9560812
TI  - [Study of hydrodynamic characteristics of artificial heart valves by photochromic
      imaging].
AB  - The paper deals with the hydrodynamics of artificial heart valves (AHVs) used in
      clinical practice. It reviews and analyzes the studies of AHV hydrodynamics, as
      well as the hydrodynamic beds which stimulate physiological flow through the
      valve. Photochronic imaging (PCI) is proposed for examination of AHV hydrodynamic
      characteristics under model physiological flow. The hydrodynamics of different
      AHVs was tested on the beds simulating blood flow through AHVs by employing PCI.
      PCI involved preparation of model photochronic solution that simulates blood,
      colour labels by using laser radiation. In the model photochronic solution, 10(
      6)-10(-9)-sec laser radiation gave rise to linear colour labels whose movement
      was recorded by a speed camera in the flow behind the valve. The profiles of
      speed behind the valves, the dimensions of congestive areas, the positions of
      flow detachment and regurgitation flow were calculated by a speed shooting in
      different periods of valvular performance. PCI defined congestive areas behind
      the valves, the areas of closed circulations, the sizes of reversing flow areas
      and examined the time course of flow behind the valves as a whole. The paper is
      of interest for AHV designers and cardiac surgeons who apply various AHVs.

PMID- 9560813
TI  - [Medical technological equipment for correction of impaired homeostasis in
      humans].
AB  - The paper considers how to correct impaired human homeostasis and to maintain it
      at an adequate level, describes some correction methods, such as an original
      method of intracorporeal detoxification and technical means for the use of these
      methods, including a perfusion roller pump that has better operating
      characteristics.

PMID- 9560814
TI  - [Experimental evaluation of materials for electrodes in transcutaneous recording
      of bioelectric signals].
AB  - The authors examined electrodes made of stainless steel, graphitic and metalized
      polymeric materials for transcutaneous recording of biopotentials from the human
      services by the following parameters: electrode potential difference, noise
      voltage, phase difference-signal frequency relationships. If the phase is
      adequately corrected, the electrode made of graphitic cloth is effective in
      recording biopotentials at an amplitude of more than 20 microV over a wide
      frequency range.

PMID- 9560816
TI  - [Cane for the blind with a device for detecting and recognizing pedestrian
      obstacles].
AB  - The paper deals with the development of methods and a device for the blind to
      walk by orientating himself through remotely contacting study of what has
      happened and is happening on the road. An optoelectron method for detection of
      vertical obstacles and ground gaps has been proposed. The authors have drawn up
      the structural and functional diagrams of a device which is combined with a
      walking-stick and which makes it possible to detect 3 types of pedestrian
      obstacles with appropriate sound signalling.

PMID- 9560815
TI  - [Theoretical substantiation and experience in vibromechanical dilatation of
      hollow organs].
AB  - The paper analyzes the principle of operation of a dilatation catheter, a device
      designed for expanding hollow organs. The organs (blood vessels, esophagus,
      cervix uteri through the cervical canal, uterine tubes) were the subject of
      investigation. The effective energy of action on the hollow organ wall in
      different catheter operations and the safety index for dilatation of hollow
      organs were defined. The aim of the study was to theoretically substantiate the
      clinical potentialities of the vibromechanical hollow organ dilatation.

PMID- 9560817
TI  - [Assessment of tolerance doses in multifractionated irradiation of the lung using
      Ellis and LQ models].
AB  - Ellis and LQ models were used to examine the tolerance dose dependences in
      different schemes of multifractionated radiation of the lung. For
      characterization of multifractionated radiation, a tolerance dose increment
      coefficient (TDIC) was introduced, which showed how the tolerance dose increased
      during multifractionated radiation as compared to the conventional scheme of dose
      fractionation with radiation given once a day. The Ellis models were shown to
      yield the TDIC values which were associated with the number of daily radiations
      rather than with the number of active days of radiation while the LQ models
      provides the TDIC values which depend not only on the number of daily radiations,
      but also on the number of active days of radiation. As the number of active
      radiation days increased, TDIC reduced. The studies were made according to a
      package of specially elaborated programmes which calculated tolerance doses in
      relation to the volume of radiation and to the scheme of dose fractionation in
      time, by using the TDF and LQ models.

PMID- 9560818
TI  - [Diagnostic unit EKS-K1200].
AB  - The paper presents the block diagram of the unit, describes some assemblies and
      its operation as a whole, gives information on the software and technical data.
      The computer-based EKS-K 1200 unit integrates a pacemaker, a 12-channel
      electrocardiograph with a monitor, and a database.

PMID- 9560819
TI  - [Results of spectral determination of metals in human tissues adjacent to K.M.
      Sivash's endoprosthesis].
AB  - The paper presents the data of semiquantitative determination of metals in the
      tissues surrounding the total titanium-comochromium endoprosthesis of the Sivash
      system. The prostheses of this design which have a point of metal-metal friction
      have been used in the past 30 years. It has been shown that chromium and cobalt
      accumulate constantly and in great quantities, molybdenum and tin do less
      frequently and in lower quantities. Seventy tissue specimens were obtained from
      20 patients followed up for 3 weeks to 15-19 years. The fine, highly sensitive
      method, emission spectral analysis, used by procedure developed by the Moscow
      Forensic Bureau of Experts was chosen. The study was undertaken to determine the
      association of the severity of metallosis with the aseptic instability of
      prostheses. However, there was no strong evidence for this: commensurable
      quantities of metals were found when permanent and temporary prostheses had been
      used. The author considers that the patients have not survived yet to have
      metallic instability that could have developed in some of them in the later
      periods of endoprosthesis use. Based on this and early studies, it is concluded
      that instability in the given periods is a result of mechanical action of some
      parts of the prostheses on bony formations. The findings show that the severity
      of metallosis depends on the number of cycles of prosthesis loading, which can be
      calculated by the duration of prosthesis use and the number of kilometers covered
      by the patient every day. The ascertained number of cycles may be correlated with
      the severity of metallosis expressed in arbitrary units.

PMID- 9560820
TI  - [Development of technical bases of radiodiagnosis].

PMID- 9560821
TI  - [Screening for thyroid diseases by using ultrasound scanners].

PMID- 9560822
TI  - Prefrontal glucose deficits in murderers lacking psychosocial deprivation.
AB  - Previous research has suggested that links between autonomic nervous system
      functioning and violence are strongest in those who come from benign home
      backgrounds, but there appears to be no similar research using brain-imaging
      measures of central nervous system functioning. It was hypothesized that
      murderers who had no early psychosocial deprivation (e.g., no childhood abuse,
      family neglect) would demonstrate lower prefrontal glucose metabolism than
      murderers with early psychosocial deprivation and a group of normal controls.
      Murderers from a previous study, which showed prefrontal deficits in murderers,
      were assessed for psychosocial deprivation and divided into those with and
      without deprivation. Murderers without any clear psychosocial deficits were
      significantly lower on prefrontal glucose metabolism than murderers with
      psychosocial deficits and controls. These results suggest that murderers lacking
      psychosocial deficits are characterized by prefrontal deficits. It is argued that
      among violent offenders without deprived home backgrounds, the "social push" to
      violence is minimized, and consequently, brain abnormalities provide a relatively
      stronger predisposition to violence in this group.

PMID- 9560823
TI  - Interhemispheric memory transfer in the intracarotid amobarbital procedure.
AB  - The authors examined interhemispheric memory transfer in 32 patients with
      lateralized temporal lobe complex partial epilepsy (15 right onsets, 17 left
      onsets). Visually presented verbal, nonverbal, and two types of dually encodable
      stimuli were displayed during amobarbital anesthesia, and recognition memory was
      tested with verbal and nonverbal (pointing) response modalities. No relationship
      was found between the material specificity of stimuli and response modality. The
      only significant findings were for poorer recognition memory after injection of
      the hemisphere contralateral to the seizure focus. Visual information presented
      predominantly to one hemisphere during anesthesia is available to the other
      hemisphere for recognition memory on clearing.

PMID- 9560824
TI  - Hippocampal cell loss and gliosis: relationship to preoperative and postoperative
      memory function.
AB  - The authors examined the relationship between neuronal densities, glial cell
      densities, and the glial cell/neuron ratio in the CA1 and CA4 hippocampal
      subfields and preoperative and postoperative memory function in 47 patients who
      had undergone a temporal lobectomy (23 right, RTL; 24 left, LTL) for the relief
      of medically intractable epilepsy. The LTL group performed more poorly than the
      RTL group on a list learning and story recall task, preoperatively and
      postoperatively. Both the RTL and LTL groups performed more poorly on the story
      recall task postoperatively. In the LTL group, neuronal densities in the CA1
      subfield were significantly correlated with the preoperative scores on the
      immediate (r = 0.53, p < 0.01) and delayed (r = 0.53, p < 0.01) recall of the
      story. There were no significant correlations in the LTL group between the CA1
      and CA4 cell counts and Verbal IQ or scores on a measure of naming ability. None
      of the cell density measures in the CA1 and CA4 subfields were significantly
      correlated with the preoperative neuropsychological test scores in the RTL group.
      Postoperative decline in verbal recall was associated with the excision of a
      relatively intact left hippocampus, with high neuronal and low glial cell
      densities in the CA1 subfield. The excision of a relatively intact right
      hippocampus was also associated with a postoperative deterioration in verbal
      recall.

PMID- 9560825
TI  - Psychologic adjustment in patients after subarachnoid hemorrhage.
AB  - A series of 45 patients after subarachnoid hemorrhage (SAH) with no or only
      marginal neurologic impairment and 36 patients with chronic obstructive pulmonary
      disease (COPD) were examined with the German Freiburger Personality Inventory
      Revised. Both groups showed a comparable frequency of psychologic impairments,
      except that the patients with COPD had significantly higher scores in the FPI-R
      bodily complaints and bodily concern subscales (p < 0.05). In the patients after
      SAH, loss of motivation (42%), abnormal introversion (40%), increased emotional
      lability (38%), and strain (31%) were found predominantly. The patients after SAH
      of unknown origin exhibited psychologic disturbances comparable with patients
      after aneurysmal SAH. A ruptured aneurysm of the anterior communicating artery
      did not lead to more psychologic disorders than aneurysms at other locations.
      Right frontal and right parietal infarctions were associated with significantly
      less emotional sensitivity (p = 0.013) and bodily concern (p < 0.001). The
      results demonstrate a substantial discrepancy between the prevalence of
      psychologic maladjustment and the moderate degree of functional impairment in
      patients after SAH, which remains to be explained by future research.

PMID- 9560826
TI  - Autosomal dominant cerebral arteriopathy: neuropsychiatric syndrome in a family.
AB  - Though familial vascular leukoencephalopathy was described two decades ago,
      recent studies focus on a disorder termed Cerebral Autosomal Dominant
      Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a
      dominantly inherited disorder causing recurrent strokes and eventual dementia.
      The phenotypic boundaries of CADASIL remain indistinct and novel clinical
      features continue to arise in the literature. However, the associated
      histopathology is fairly consistent, typically demonstrating granular thickening
      of cerebral arterioles. The authors evaluated a 38-year-old man who suffered from
      progressive change in personality and intellect. His father, paternal aunt, and
      older sister had succumbed to a similar disorder. The authors examined relatives
      from three generations, including another sister with transient focal symptoms
      followed by persisting psychiatric disorder, and reviewed the radiographic
      studies from the propositus and his siblings. All the siblings showed diffuse
      white matter signal change on magnetic resonance imaging. Brain biopsy from the
      propositus revealed normal cortex and white matter but granular sclerosis of
      leptomeningeal arterioles. While the family's illness likely represents another
      instance of CADASIL, their presentation is unique because neuropsychiatric
      disorders predominate over focal ischemic symptoms.

PMID- 9560827
TI  - Persistent recurrence of hypomania and prosopoaffective agnosia in a patient with
      right thalamic infarct.
AB  - The authors report a 63-year-old man with a history of brief isolated manic
      episodes who became persistently hypomanic after a small right thalamic infarct.
      Detailed behavioral and neuropsychologic assessment were performed 18 months
      after the stroke and revealed a prosopoaffective agnosia as the foremost
      cognitive disorder, i.e., an impairment in the identification of emotional facial
      expressions with preserved discrimination of facial identity. Difficulties in
      reasoning on humorous material and other signs of mild right hemisphere
      dysfunction were present, but other perceptual, frontal and abstract-reasoning
      cognitive functions were unimpaired. Prosopoaffective agnosia has not been
      reported previously in thalamic lesions or in primary or secondary mania. The
      authors discuss the hypothetical relationships between a right hemisphere deficit
      in processing emotions and relapsing of the patient's hypomanic behavior.

PMID- 9560829
TI  - Managing patients with vulvovaginal candidiasis.
AB  - Epidemiologic studies have demonstrated a continuing increase in the prevalence
      of vulvovaginal candidiasis. Although in the past most of these infections were
      caused by Candida albicans, an increasing percentage are caused by non-albicans
      Candida species that are less sensitive to the most frequently used antifungal
      agents. An accurate diagnosis of these infections and the subsequent choice of
      the most appropriate therapy can only be made after a thorough evaluation of the
      patient. Successful treatment of vulvovaginal candidiasis is dependent on
      compliance with therapy; thus, the treatment regimen chosen should fit the
      patient's daily lifestyle. Newer single-dose regimens offer the option of
      completing therapy with a single treatment for most patients with uncomplicated
      vaginal candidiasis. Use of topical agents avoids the potential systemic adverse
      effects and drug interactions that have been noted with oral antifungals. Patient
      education and support can also enhance satisfaction with the treatment plan and
      promote compliance.

PMID- 9560828
TI  - Screening, diagnosis, and management of prostate cancer: improving primary care
      outcomes.
AB  - Prostate cancer (PC) resulted in more than 41,000 related deaths in 1996.
      However, much confusion exists about when and whom to screen and treat for PC.
      Guidelines opposing the early detection and treatment of PC are based on outcomes
      from diagnoses and treatments made prior to recent improvements in screening and
      treatment methods. More recently, prostate specific antigen has been shown to be
      both specific and sensitive in detecting PC at an early, curable stage. Several
      options for treating early PC now exist: anatomic radical prostatectomy, external
      beam radiation, implanted radiation seeds, and cryotherapy. Informed primary care
      providers have an opportunity to make individualized, rational decisions that
      will promote better outcomes for men with PC.

PMID- 9560830
TI  - A comprehensive approach to bereavement.
AB  - Bereavement is associated with significant mental and physical health
      consequences, and risk factors for illness associated with bereavement have been
      demonstrated. Although bereavement cannot be eliminated as a health risk, primary
      care providers can screen for it, facilitate the normal grief process, and
      mitigate risks for bereavement complications and health deterioration.
      Considering the time constraints in today's fast-paced health care environment,
      this article offers a clear and comprehensive framework for primary care of
      grieving people. The framework presented here includes (1) empirically shown risk
      factors for health deterioration in bereavement; (2) an assessment and screening
      patient history format suitable for primary bereavement care; (3) primary care
      guidelines for differential diagnosis of bereavement; and (4) principles of
      primary care for the bereaved. This article also addresses primary care for
      bereaved children, parents, and other specific bereaved populations, and
      discusses pharmacotherapy and multicultural considerations in bereavement.

PMID- 9560831
TI  - Diagnosing pediatric epilepsy: an update for the primary care clinician.
AB  - Epilepsy is a chronic disorder that first appears in childhood. Seizure types and
      presentation vary from dramatic and obvious to subtle and discrete. Accurate
      identification of the seizure type is imperative to ensure proper disease
      management. The International league Against Epilepsy has developed two
      classification systems--the classification of Epileptic Seizures and the
      classification of Epilepsies and Epileptic Syndromes--to assist in the provision
      of an International language of epilepsy, to improve the diagnosis and management
      of seizures, and to establish prognostic criteria. Knowledge of the
      classification systems of seizures, seizure types, and management of seizures is
      essential in the delivery of health promotion, disease prevention, and
      anticipatory guidance for the child with epilepsy. The primary care practitioner
      is often the first person consulted when medical questions or problems arise, and
      therefore is in a key position to detect seizures, monitor treatment, and educate
      the family. A comprehensive knowledge of pediatric epilepsy will allow the
      practitioner to provide the additional resources needed to coordinate the care of
      this special population.

PMID- 9560832
TI  - Low molecular weight heparins: the future of thromboembolic therapy.

PMID- 9560833
TI  - Pathogenesis of preeclampsia: a comprehensive model.
AB  - The objective of this review was to provide a comprehensive and practical concept
      on the pathogenesis of preeclampsia on the basis of the currently available
      scientific evidence. A MEDLINE search was performed of English-language articles
      published between 1966 and 1997, supplemented with references cited in relevant
      research articles. Using our data sources, we developed a scheme describing the
      sequence of events between implantation and the time of manifest clinical disease
      characterized by generalized endothelial cell dysfunction. A yet unidentified
      toxic circulating factor released by the ischemic placenta, is held responsible
      for the impaired endothelial cell function. Particularly, epidemiological studies
      point to a concept in which immune maladaptation to the fetal allograft plays a
      key role in causing defective placentation leading to placental ischaemia. The
      incidence of preeclampsia in sisters and daughters of women who had had
      preeclampsia is raised. Disease states with vascular involvement, like chronic
      hypertension and diabetes mellites, are associated with an increased risk for
      preeclampsia. Recently subclinical abnormalities in hemostasis, metabolism and
      volume homeostasis have been described in patients with a history of
      preeclampsia. Placental ischemia secondary to defective placentation, a
      prerequisite for the development of preeclampsia, has a multifactorial origin
      consisting of three major components: immune maladaptation, genetic
      predisposition, and vascular mediated factors. Probably, a summation of these
      factors will determine whether a pregnant woman is to develop the syndrome. The
      recently described subclinical abnormalities in hemostasis, metabolism, and
      vascular function in patients with a history of preeclampsia might give the
      clinician the opportunity to reduce the recurrence risk by pharmacotherapeutic
      intervention.

PMID- 9560834
TI  - Granulosa and theca cell tumors in children: a report of 17 cases and literature
      review.
AB  - The files of the Emil Novak Ovarian Tumor Registry (ENOTR) were searched for
      granulosa and theca cell tumors in children aged 12 years and less. In addition,
      an extensive literature search was done for English publications on children with
      these tumors aged 10 years or less. Of the 17 children from the ENOTR, 5 had
      adult-type granulosa cell tumors, 6 had juvenile granulosa cell tumors, and 1 had
      a luteinized granulosa cell tumor. In addition, there were three cases with
      gonadal stomal tumors, one theca cell tumor, and one granulosa-theca cell tumor.
      Precocious pseudopuberty was present in 70 percent of the children, abdominal
      pain in 24 percent, and ascites in 18 percent. The literature review revealed a
      tumor-related mortality rate of 9 percent (based on 163 cases with granulosa cell
      tumors, including the juvenile type). Some of these tumors are large with acute
      pain, but nevertheless, the prognosis is good, particularly in cases with
      precocious puberty. Treatment can be conservative.

PMID- 9560835
TI  - The genetics of ovarian cancer: molecular biology and clinical application.
AB  - Ovarian cancer is the fifth most common malignancy among American women and the
      fourth leading cause of cancer death. The rapid advances in molecular genetic
      analysis, presymptomatic detection, and treatment of ovarian cancer are
      staggering. In this review, both the genetic component and the molecular biology
      of ovarian cancer are discussed, as well as current recommendations for genetic
      counseling. It is important for the practicing obstetrician and gynecologist to
      become familiar with these concepts, for it is he or she who will likely serve as
      a primary resource of information for these patients.

PMID- 9560836
TI  - New insights into steroid resistant asthma.
AB  - The term "steroid resistant (SR) asthma" refers to a group of asthmatics who have
      persistent airway obstruction and immune activation despite treatment with high
      doses of systemic glucocorticoids. There are at least two forms of SR asthma,
      i.e. primary and acquired types. Type I SR asthma is acquired and is associated
      with abnormally reduced glucocorticoid receptor (GCR) ligand and DNA binding
      affinity. Type II SR asthma appears to be due to a constitutive defect and is
      associated with low numbers of GCRs. An important distinction between these two
      types of SR asthma is that the GCR defect in Type I, but not Type II, SR asthma
      is reversible in culture and is sustained by incubation with combination IL-2 and
      IL-4. Recent studies suggest that the abnormal GCR binding in Type I SR asthma
      may be due to cytokine-driven alternative splicing of the GCR pre-mRNA to a novel
      isoform called GCRbeta which does not bind glucocorticoids but antagonizes the
      transactivating activity of the classic GCR. These GCR changes along with recent
      evidence for increased transcription factor activation in SR asthma which may
      inhibit GCR/DNA interactions as well as the selective recruitment of neutrophils
      into the airways of certain patients with severe asthma contribute to the
      heterogeneity of mechanisms underlying steroid resistance.

PMID- 9560837
TI  - Randomised controlled trial of advice on an egg exclusion diet in young children
      with atopic eczema and sensitivity to eggs.
AB  - BACKGROUND: The role of exclusion diets in the management of atopic eczema in
      young children is uncertain. This randomised controlled trial evaluates the
      effect of excluding egg from the diet in young children with atopic eczema and
      sensitivity to eggs. Fifty-five such children were randomised either to a 4-week
      regimen, in which mothers were given general advice on care of eczema and
      additional specific advice from a dietician about an egg exclusion diet (diet
      group), or to a control group in which general advice only was given. Both groups
      continued conventional topical treatment. Disease activity was assessed by
      estimates of the surface area affected by eczema and by an arbitrary severity
      score. Possible egg sensitivity was identified by RAST before randomisation and
      after the trial by double-blind placebo-controlled egg challenge. RESULTS: The
      mean reduction in surface area affected by eczema was significantly greater (p =
      0.02) in the group receiving dietary advice (from 19.6% to 10.9% area affected)
      than in the control group (from 21.9% to 18.9%). A significant improvement also
      occurred in severity score (p = 0.04): from 33.9 to 24.0 units for the diet group
      compared with a decrease from 36.7 to 33.5 in the control group. The study
      suggests that advice on the dietary exclusion of eggs is useful as part of the
      overall management of young children with atopic eczema and sensitivity to eggs.

PMID- 9560839
TI  - Concentrations of cat (Fel d1), dog (Can f1) and mite (Der f1 and Der p1)
      allergens in the clothing and school environment of Swedish schoolchildren with
      and without pets at home.
AB  - To investigate whether our hypothesis that cat and dog owners bring allergens to
      public areas in their clothes was true or not, we studied the levels of Fel d1,
      Can f1, Der p1 and Der f1 in dust from the clothes and classrooms of children in
      a Swedish school. We also investigated the levels of allergen in different areas
      in the four classrooms used by the children. Thirty-one children were selected in
      four classes, forming three groups: cat owners, dog owners and children without a
      cat or dog at home. Furthermore, a group of children with asthma was included.
      Cat and dog allergens were detected in all 57 samples from clothes and
      classrooms. Mite allergen Der f1 was detected in low concentrations in 6 out of
      48 and Der p1 in 5 out of 46 samples investigated. The concentrations of Can f1
      were higher than those of Fel d1 in samples from clothes (geometric mean: 2676
      ng/g fine dust and 444 ng/g) and classrooms (Can f1: 1092 ng/g, Fel d1: 240
      ng/g). The dog owners had significantly higher concentrations of Can f1 (8434
      ng/g fine dust) in their clothes than cat owners (1629 ng/g, p < 0.01), children
      without cat or dog (2742 ng/g, p < 0.05) and children with asthma (1518 ng/g, p <
      0001). The cat owners did not have significantly higher levels of Fel d1 (1105
      ng/g) in their clothes compared to the other three groups. (D: 247 ng/g, nCnD:
      418 ng/g) but the levels were significantly higher than for all children without
      a cat at home (345 ng/g, p < 0.05). No concentrations of mite allergen and low
      concentrations of Fel d1 and Can f1 were found in the children's hair. There were
      significantly higher concentrations of Fel d1 and Can f1 in dust from curtains
      than in samples from floors and bookshelves (p < 0.05). There was no significant
      difference between the allergen concentrations in samples from curtains and from
      desks and chairs, including the teachers' chairs, the only upholstered furniture
      in the rooms. Our results support the hypothesis that cat and dog owners bring
      allergens to public areas in their clothes and support other studies showing that
      textiles and upholstered furniture function as reservoirs of cat and dog
      allergens. Thus, children with asthma and other allergic diseases will be exposed
      to cat and dog allergens at school and by contact with pet owners, even if they
      avoid animal allergens at home.

PMID- 9560838
TI  - Time course of changes in the intestinal permeability of food-sensitized rats
      after oral allergen challenge.
AB  - Rats were sensitized with ovalbumin (OVA) with a molecular weight of 45 kd,
      challenged with OVA orally, followed by orally administered beta-lactoglobulin
      (BLG) as an intestinal permeability marker. BLG is a macro-molecular protein with
      a molecular weight of 18 kd. Blood BLG concentrations were measured (by ELISA)
      serially over 4 hours following BLG administration, which in turn was given 1
      hour after OVA challenges. The maximum BLG concentration was at 2 hours. BLG was
      then administered orally 1, 3, 6, 12 and 24 hours after oral OVA challenge, and
      the serum BLG concentration at 2 hours after BLG administration was compared
      among the five groups. BLG appeared in the circulation of the animals 1, 6 and 24
      hours after allergen challenge, but not after 3 and 12 hours. The serum BLG
      concentration was not significantly different at 1, 6 and 24 hours.
      Histopathological examinations of the intestines showed mast cell infiltration of
      the intestinal mucosa at 1 hour, remarkable edema of villi at 3 hours, eosinophil
      infiltration at 6 hours, an increase of goblet cells at 12 hours and villous
      atrophy and lymphocyte infiltration at 24 hours. The appearance in the serum of
      three BLG peaks of comparable heights suggested that the intestinal absorption of
      BLG may be related to a late and delayed phase as well as the immediate IgE
      dependent phase response.

PMID- 9560840
TI  - Cat and dog allergen in mattresses and textile covered floors of homes which do
      or do not have pets, either in the past or currently.
AB  - The aim of this study was to measure the levels of cat and dog allergen in homes
      of families that had either never kept pets or kept or had kept cats or dogs.
      From a small residential area outside Stockholm consisting of 250 houses with
      similar exteriors 70 homes were included. Dust samples were collected from
      mattresses and textile-covered floors. The levels of cat and dog allergen were
      analysed by ELISA. Fel d1 was found in mattress dust in all 70 homes, median 0.5
      micrograms/g [0.24-8.89 micrograms/g (quartiles)] and textile-covered floors 0.7
      micrograms/g (0.20-2.52 micrograms/g). Can f1, was found in 98% of the collected
      samples, mattress dust 1.89 micrograms/g (0.70-9.20 micrograms/g) and textile
      covered floor dust 2.5 micrograms/g (1.04-2.72 micrograms/g). There was a
      positive correlation (p < 0.001) between allergen levels in dust from mattresses
      and textile-covered floors for both Fel d1 (r = 0.68) and Can f1 (r = 0.78). The
      highest levels of cat and dog allergen were found in homes with furred pets (p <
      0.001). A significant (p < 0.001) difference was seen in the levels of Fel d1 and
      Can f1 between the homes of former pet-owners and homes without pets. In summary;
      cat and dog allergens are present in homes regardless of whether such animals
      live in the house or not. Mattresses seem to be an underestimated reservoir for
      pet allergens even in homes without pets. It is important to note that the homes
      of former pet owners have much lower levels of allergen than current pet owners.

PMID- 9560841
TI  - Development of latex allergy in children up to 5 years of age--a retrospective
      analysis of risk factors.
AB  - The aim of the study was to investigate possible associations between the time
      course of early sensitization to latex and various life style factors. Of the 398
      children from a prospective birth cohort study, 20 (5%) showed specific serum IgE
      to latex at the age of 5 years. Sensitization started beyond the first year of
      life and 19 out of 20 sensitized children showed increasing specific IgE-values
      over time. All 20 sensitized children were atopic (p < 0.00000). Total IgE was
      significantly higher in the sensitized group (median 394.5 kU/I) than in the non
      sensitized group (median 39.2 kU/l) (p < 0.00001). Comparing the latex-sensitized
      group with the non-sensitized children, there were significantly more operations
      in the latex group (p < 0.05) during the first 5 years of life. Medical history,
      certain foods, the use of pacifiers, mattress composition and socio-economic data
      proved not to be significant risk factors. From our study we conclude that
      besides the number of operations and an atopic predisposition--no other definite
      risk factor for developing sensitization or allergy to latex (such as everyday
      household objects) can be identified in children up to 5 years of age.

PMID- 9560842
TI  - Longitudinal study on latex sensitization in children with spina bifida.
AB  - The course of latex sensitization is rarely documented, and only a few reports
      about the influence of prophylaxis in the occupational environment have been
      published concerning health care workers. Therefore we did a follow-up study in
      the high risk group of patients with spina bifida and evaluated the efficacy of
      latex prophylaxis. For this purpose we measured IgE antibodies (FEIA) against
      latex and inhalative allergens in the sera of 67 patients with spina bifida and
      reevaluated them 0.6 to 4.1 years later, having instructed the patients about
      prophylactic measures and established a latex-free environment for surgery of all
      spina bifida patients in our hospital. 37% of the patients did not develop latex
      antibodies during the follow-up period, 27% showed decreasing levels of
      antibodies (12% to non-detectable levels), 19% had an increase in latex
      sensitization (6% newly sensitized), and 9% showed no change in levels of latex
      antibodies. From our data it may be concluded that surgery without strict latex
      prophylaxis is the main cause of new sensitization and worsening of preexisting
      latex antibody levels. Mild sensitization can be reduced by prophylactic
      measurements to non-detectable antibody levels. With consistent prophylaxis, even
      symptomatic patients can be operated without risk of allergic complications or
      increasing antibodies.

PMID- 9560843
TI  - Lymphocyte subset reference ranges in healthy Saudi Arabian children.
AB  - In an attempt to establish the reference ranges for lymphocyte subsets in
      children, the distribution of lymphocyte population-bearing surface markers such
      as CD3 (T cells), CD19 (B cells), CD4 (T helper/inducer cells), CD8 (T
      suppressor/cytotoxic cells), and CD16 and/or CD56 on CD3- cells (NK cells) has
      been studied among healthy Saudi Arabian infants and children. Normal adult blood
      donors were used for comparison. Anticoagulated peripheral blood was stained with
      monoclonal antibodies and the lymphocytes were analyzed by flow cytometry for the
      expression of the above markers. Absolute and percentage values for most
      lymphocyte populations differed substantially not only between children and
      adults but also among children from different age groups. Absolute numbers of all
      the lymphocyte subsets decreased with age from 1 month to 13 years; the median
      value declined from 4.1 to 1.9 (T cells), 1.6 to 0.6 (B cells), 0.5 to 0.3 (NK
      cells), 2.7 to 1.0 (CD4+ T cells) and 1.5 to 0.8 x 10(3) cells/mm3 (CD8+ T
      cells). HLA-DR+ T cell counts changed significantly from 0.3 to 0.2 x 10 (3)
      cells/mm3 during the same age period. In contrast, the lymphocyte percentage
      increased in all the subsets except B cells and CD4+ T cells with time. The
      percentage values increased from 66 to 74 (T cells), 8 to 11 (NK cells), 23 to 39
      (CD8+ T cells) and 4 to 9 (HLA-DR+ T cells). The values changed from 24 to 12 and
      46 to 39 for B cells and CD4+ T cells, respectively, with age from 1 month to 13
      years. The variations in CD4+ and CD8+ T cells resulted in a decrease in
      CD4+/CD8+ ratio from 2.0 to 1.1 with age. These data should be useful as
      reference values for lymphocyte subsets in various diseases of infants and
      children.

PMID- 9560844
TI  - Thymoma and cellular immune deficiency in an adolescent.
AB  - Thymoma has been associated with both humoral immunodeficiency and cellular
      immunodeficiency, but the latter association has never been described in the
      pediatric age group. We report a 15-year-old female with thymoma, recalcitrant
      oropharyngeal candidiasis, recurrent generalized cutaneous herpes simplex virus
      type 2 infection, recurrent pneumonia and myasthenia gravis. Pathology of the
      thymic lesion showed a 10x5x6 cm extensively hyalinized mass with residual
      regions of spindle cell predominant and lymphocyte-rich thymoma. There was no
      evidence of humoral immunodeficiency but there was clinical and laboratory
      evidence of cellular immunodeficiency with cutaneous anergy and absence of T cell
      proliferation to Candida antigen. Six weeks after the thymoma was resected, she
      was no longer anergic and Candida proliferation was normal, although she
      continued to experience infections. This is the first reported pediatric patient
      with an association of cellular immunodeficiency with thymoma.

PMID- 9560845
TI  - Pathology of idiopathic dystonia: findings from genetic animal models.
AB  - Dystonia is a common movement disorder which is thought to represent a disease of
      the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e.
      the neuroanatomic and neurochemical basis, is still a mystery. Research in
      dystonia is complicated by the existence of various phenotypic and genotypic
      subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.
      In neurological diseases in which no obvious neuronal degeneration can be found,
      such as in idiopathic dystonia, the identification of a primary defect is
      difficult, because of the large number of chemically distinct, but functionally
      interrelated, neurotransmitter systems in the brain. The variable response to
      pharmacological agents in patients with idiopathic dystonia supports the notion
      that the underlying biochemical dysfunctions vary in the subtypes of idiopathic
      dystonia. Hence, in basic research it is important to clearly define the involved
      type of dystonia. Animal models of dystonias were described as limited. However,
      over the last years, there has been considerable progress in the evaluation of
      animal models for different types of dystonia. Apart from animal models of
      symptomatic dystonia, genetic animal models with inherited dystonia which occurs
      in the absence of pathomorphological alterations in brain and spinal cord are
      describe. This review will focus mainly on genetic animal models of different
      idiopathic dystonias and pathophysiological findings. In particular, in the case
      of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case
      of the genetically dystonic hamster (dt(sz)), a model of paroxysmal dystonic
      choreoathetosis has been used, as these show great promise in contributing to the
      identification of underlying mechanisms in idiopathic dystonias, although even a
      proper animal model will probably never be equivalent to a human disease. Several
      pathophysiological findings from animal models are in line with clinical
      observations in dystonic patients, indicating abnormalities not only in the basal
      ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through
      clinical studies and neurochemical data several similarities were found in the
      genetic animal models, although the current data indicates different defects in
      dystonic animals which is consistent with the notion that dystonia is a
      heterogenous disorder. Different supraspinal dysfunctions appear to lead to
      manifestation of dystonic movements and postures. In addition to increasing our
      understanding of the pathophysiology of idiopathic dystonia, animal models may
      help to improve therapeutic strategies for this movement disorder.

PMID- 9560846
TI  - The role of excitatory amino acids in behavioral sensitization to psychomotor
      stimulants.
AB  - Behavioral sensitization refers to the progressive augmentation of behavioral
      responses to psychomotor stimulants that develops during their repeated
      administration and persists even after long periods of withdrawal. It provides an
      animal model for the intensification of drug craving believed to underlie
      addiction in humans. Mechanistic similarities between sensitization and other
      forms of neuronal plasticity were first suggested on the basis of the ability of
      N-methyl-D-aspartate (NMDA) receptor antagonists to prevent the development of
      sensitization [Karler, R., Calder, L. D., Chaudhry, I. A. and Turkanis, S. A.
      (1989) Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801. Life
      Sci., 45, 599-606]. This article will review the large number of subsequent
      studies addressing: (1) the roles of NMDA, alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionate (AMPA) and metabotropic glutamate receptors in the
      development and expression of behavioral sensitization, (2) excitatory amino
      acids (EAAs) and the role of conditioning in sensitization, (3) controversies
      regarding EAA involvement in behavioral sensitization based on studies with MK
      801, (4) the effects of acute and repeated stimulant administration on EAA
      neurochemistry and EAA receptor expression, and (5) the neuroanatomy of EAA
      involvement in sensitization. To summarize, NMDA, AMPA metabotropic glutamate
      receptors all participate in the development of sensitization, while maintenance
      of the sensitized state involves alterations in neurochemical measures of EAA
      transmission as well as in the expression and sensitivity of AMPA and NMDA
      receptors. While behavioral sensitization likely involves complex neuronal
      circuits, with EAAs participating at several points within this circuitry, EAA
      projections originating in prefrontal cortex may play a particularly important
      role in the development of sensitization, perhaps via their regulatory effects on
      midbrain dopamine neurons. The review concludes by critically evaluating various
      hypotheses to account for EAA involvement in the development of behavioral
      sensitization, and considering the question of whether EAA receptors are involved
      in mediating the rewarding effects of psychomotor stimulants and sensitization of
      such rewarding effects.

PMID- 9560847
TI  - Pharmacology of glutamate receptor antagonists in the kindling model of epilepsy.
AB  - It is widely accepted that excitatory amino acid transmitters such as glutamate
      are involved in the initiation of seizures and their propagation. Most attention
      has been directed to synapses using NMDA receptors, but more recent evidence
      indicates potential roles for ionotropic non-NMDA (AMPA/kainate) and metabotropic
      glutamate receptors as well. Based on the role of glutamate in the development
      and expression of seizures, antagonism of glutamate receptors has long been
      thought to provide a rational strategy in the search for new, effective
      anticonvulsant drugs. Furthermore, because glutamate receptor antagonists,
      particularly those acting on NMDA receptors, protect effectively in the induction
      of kindling, it was suggested that they may have utility in epilepsy prophylaxis,
      for example, after head trauma. However, first clinical trials with competitive
      and uncompetitive NMDA receptor antagonists in patients with partial (focal)
      seizures, showed that these drugs lack convincing anticonvulsant activity but
      induce severe neurotoxic adverse effects in doses which were well tolerated in
      healthy volunteers. Interestingly, the only animal model which predicted the
      unfavorable clinical activity of competitive NMDA antagonists in patients with
      chronic epilepsy was the kindling model of temporal lobe epilepsy, indicating
      that this model should be used in the search for more effective and less toxic
      glutamate receptor antagonists. In this review, results from a large series of
      experiments on different categories of glutamate receptor antagonists in fully
      kindled rats are summarized and discussed. NMDA antagonists, irrespective whether
      they are competitive, high- or low-affinity uncompetitive, glycine site or
      polyamine site antagonists, do not counteract focal seizure activity and only
      weakly, if at all, attenuate propagation to secondarily generalized seizures in
      this model, indicating that once kindling is established, NMDA receptors are not
      critical for the expression of fully kindled seizures. In contrast, ionotropic
      non-NMDA receptor antagonists exert potent anticonvulsant effects on both
      initiation and propagation of kindled seizures. This effect can be markedly
      potentiated by combination with low doses of NMDA antagonists, suggesting that an
      optimal treatment of focal and secondarily generalized seizures may require
      combined use of both non-NMDA and NMDA antagonists. Given the promising results
      obtained with novel AMPA/kainate antagonists and glycine/NMDA partial agonists in
      the kindling model, the hope for soon having potentially useful glutamate
      antagonists for use in epileptic patients is increasing.

PMID- 9560848
TI  - An international look at adolescent health promotion.

PMID- 9560849
TI  - [The measure of the quality of life of adolescents: a new evaluation tool of
      their health needs for a new educational approach?].
AB  - Hundreds of studies carried out in the past 20 years have worked on youth and
      adolescent health indicators linked to general morbidity and mortality and to
      specific pathologies. The majority of research has focused on evaluating the
      impact of risk behaviours such as tobacco, alcohol and drug use, non-protected
      sexual intercourse, and unbalanced nutrition on the health of youth. The
      usefulness of medical care and health education programmes has thus traditionally
      been evaluated on the basis of their impact on mortality and morbidity. However,
      these measures have proven insufficient and the necessity to pay more attention
      to quality, and not only length of life is now apparent. This article focuses on
      the question of whether the tool for measuring quality of life linked to health,
      adapted from what now exists for "sick" adolescents, can constitute a new
      indicator allowing for evaluation of the unknown realm of adolescent health
      needs. The authors address the concept of measuring the quality of life by
      providing several of its definitions, noting the difficulties and insufficiencies
      of their measurement. The authors also wonder why the multiple professionals
      preoccupied with adolescent health have not yet imagined using a participative
      approach to developing these measures, i.e. an approach including the adolescents
      themselves, has not been used. The authors propose that to include adolescents in
      the development of evaluation tools would ensure that the adolescent's needs for
      expression and to be heard are fulfilled. The authors also maintain that
      education, both health and general, should enable individuals to understand what
      is positive within themselves, and thus develop these aspects to their fullest.
      It should not force models of behaviour onto individuals or groups. If this
      approach is taken in developing quality of life indicators for young people, a
      positive health promotion approach to enabling adolescents can be developed.

PMID- 9560850
TI  - Indicators of adolescent health: expanding the framework for assessing health
      status among young people.

PMID- 9560851
TI  - Community perceptions regarding critical adolescent sexual and reproductive
      health: needs and solutions.

PMID- 9560852
TI  - An investigation of adolescent health in Vietnam: sexual behaviour and attitudes
      of adolescents.

PMID- 9560853
TI  - Using the Internet to engage youth in health promotion.

PMID- 9560854
TI  - [Promotion of orodental health in adolescents in Africa].
AB  - Bad dental hygiene in adults is usually the result of bad care during childhood.
      Within the framework of Health for All, WHO and the International Dental
      Federation defined global objectives for dental health which allow for monitoring
      progress in different countries. The most common dental problems, such as dental
      cavities, can be prevented by simple and inexpensive methods. Dental health is
      based on dental hygiene, nutrition, fluoride intake and dental service
      utilisation. Dental health promotion aims to create an environment favourable to
      the adoption of these healthy behaviours. The principle recommended dental health
      measures are through fluoridation of water, salt, and milk, a low consumption of
      sweets, and modification of the amount of sugar in the diet; implementation of
      monitored dental hygiene activities in schools; the organisation of regular
      dental services in schools/workplaces; and adopting legislative texts or laws
      requiring certain measures of prevention. In the past several years, certain
      African countries have set up national dental health programmes (there were 12 in
      1993), However, the implementation of dental health promotion generally doesn't
      result from a national initiative, but from a regional or local scale. This is
      largely due to the lack of integration of dental health in activities of
      education and health promotion in general. Programmes planned at a national level
      and then implemented at a local level on a multisectoral base have had more
      success. This article presents examples of dental health promotion activities in
      several African countries, mainly focusing on programmes aimed at 12-13 year olds
      in primary school. Programmes from Morocco, Kenya, Madagascar, Cote d'Ivoire,
      Benin, and Tanzania are briefly presented and show that in Africa, dental health
      promotion has mostly consisted of the implementation of health education actions
      and that there are no consistent policies, unlike in other developing countries,
      for fluoridation of water, salt, and milk. In terms of dental health promotion,
      WHO recommends the promotion of traditional methods of dental hygiene (such as
      plants or sticks for cleaning), especially among adolescents living in rural and
      low income communities. In turn, the identification and promotion of the positive
      aspects of hygiene and traditional care will allow for the implementation of more
      culturally acceptable approaches.

PMID- 9560855
TI  - [Health promotion in adolescents in Latin America].
AB  - The First International Conference on Health Promotion (Ottawa 1996) consolidated
      and developed the interest of Latin American countries in the amelioration of the
      health of their populations. Initiatives such as the International Conference for
      Health Promotion in Columbia in 1992 and the adoption in 1993 of the Caribbean
      Charter for Health Promotion show the efforts that have been carried out by
      different American countries to work toward the principles of the Ottawa Charter
      and to adapt them to their realities. This article focuses on the state of health
      of adolescents in Latin America as well as different actions that have been, and
      continue to be, carried out. The authors first discuss the peer approach to
      health education, which has been used in many health promotion actions throughout
      Latin America because of its effectiveness. Often in developing countries, the
      oldest children care for the younger ones. This approach therefore provides a way
      to reach not only peers of the adolescent involved, but also other youth in
      his/her entourage. Also, the participation of youth in health education allows
      them to develop relations with adults outside of their families, to improve their
      self-perceptions and to acquire a sense of responsibility and belonging within a
      social group. Examples from several countries are provided by the authors. What
      the authors call "classic" approaches to health promotion and education are also
      still used in many countries of Latin America and many of these programmes are
      concerned with sexual education and managing adolescent parenthood. Also,
      programmes using in approach specific to problems such as alcoholism, drug abuse,
      and violence have been developed in many countries. Finally, training programmes
      for health personnel focusing on the specific health needs of adolescents have
      been developed in Brazil, Peru, Costa Rica, and Uruguay for a large range of
      health professionals (psychologists, social workers, etc.). In conclusion, the
      authors state that although there is an increasing number of health promotion
      actions for adolescents in Latin America, there is still much work to be done.
      One of the elements that is priority for managing the health of adolescents is
      the integral approach of the adolescent, considering the psychological, social,
      and environmental factors that influence his/her well-being. Multi-disciplinary
      and intersectoral approaches are also considered as important, as is the
      participation of adolescents in the development and implementation of actions
      concerning them.

PMID- 9560856
TI  - Frameworks to inform the development of U.S. adolescent health indicators for the
      21st century.

PMID- 9560857
TI  - Adolescent health today: contributions and limitations of epidemiology, facts,
      doubts and uncertainties.

PMID- 9560858
TI  - Improving the health of youth through a coordinated school health programme.

PMID- 9560859
TI  - Lessons derived from evaluating Gulf War syndrome: suggested guidelines for
      investigating possible outbreaks of new diseases.

PMID- 9560860
TI  - Reducing the need and demand for medical services.

PMID- 9560862
TI  - Gender differences in the reporting of physical and somatoform symptoms.
AB  - OBJECTIVE: Women have consistently been shown to report greater numbers of
      physical symptoms. Our aim in this study was to assess gender differences for
      specific symptoms and to assess how much of these differences were attributable
      to psychiatric comorbidity. METHOD: Data from the PRIME-MD 1000 study (1000
      patients from four primary case sites evaluated with the Primary Care Evaluation
      of Mental Disorders interview) were analyzed to determine gender differences in
      the reporting of 13 common physical symptoms. The effect of gender on symptom
      reporting was assessed by multivariate analysis, adjusting for depressive and
      anxiety disorders as well as age, race, education, and medical comorbidity.
      RESULTS: All symptoms except one were reported more commonly by women, with the
      adjusted odds ratios (typically in the 1.5-2.5 range) showing statistically
      significant differences for 10 of 13 symptoms. Somatoform (ie, physically
      unexplained) symptoms were also more frequent in women. Although depressive and
      anxiety disorders were the strongest correlate of symptom reporting, gender had
      an independent effect that persisted even after adjusting for psychiatric
      comorbidity. Gender was the most important demographic factor associated with
      symptom reporting, followed by education. CONCLUSIONS: Most physical symptoms are
      typically reported at least 50% more often by women than by men. Although mental
      disorders are also more prevalent in women, gender influences symptom reporting
      in patients whether or not there is psychiatric comorbidity.

PMID- 9560861
TI  - Treatment costs, cost offset, and cost-effectiveness of collaborative management
      of depression.
AB  - OBJECTIVE: The report estimates the treatment costs, cost-offset effects, and
      cost-effectiveness of Collaborative Care of depressive illness in primary care.
      STUDY DESIGN: Treatment costs, cost-offset effects, and cost-effectiveness were
      assessed in two randomized, controlled trials. In the first randomized trail (N =
      217), consulting psychiatrists provide enhanced management of pharmacotherapy and
      brief psychoeducational interventions to enhance adherence. In the second
      randomized trial (N = 153). Collaborative Care was implemented through brief
      cognitive-behavioral therapy and enhanced patient education. Consulting
      psychologist provided brief psychotherapy supplemented by educational materials
      and enhanced pharmacotherapy management. RESULTS: Collaborative Care increased
      the costs of treating depression largely because of the extra visits required to
      provide the interventions. There was a modest cost offset due to reduced use of
      specialty mental health services among Collaborative Care patients, but costs of
      ambulatory medical care services did not differ significantly between the
      intervention and control groups. Among patients with major depression there was a
      modest increase in cost-effectiveness. The cost per patient successfully treated
      was lower for Collaborative Care than for Usual Care patients. For patients with
      minor depression. Collaborative Care was more costly and not more cost-effective
      than Usual Care. CONCLUSIONS: Collaborative Care increased depression treatment
      costs and improved the cost-effectiveness of treatment for patients with major
      depression. A cost offset in specialty mental health costs, but not medical care
      costs, was observed. Collaborative Care may provide a means of increasing the
      value of treatment services for major depression.

PMID- 9560863
TI  - The stability of family decisions to consent or refuse organ donation: would you
      do it again?
AB  - OBJECTIVE: Past organ donation research has studied attitudes toward donation,
      predictors of signing donor cards, and distinguishing characteristics of donors
      vs. nondonors. The current study is the first to examine predictors of family
      members' satisfaction with the decision to consent or refuse donation of a dying
      loved one's organs or tissue. METHOD: This study surveyed 225 family members who
      had been approached to donate the organs or tissue of a dying loved one.
      Participants were surveyed about demographic characteristics, medical/hospital
      factors, previous knowledge of transplantation, the request process, religion,
      and characteristics of the deceased and of the recipient. Discriminant analyses
      were conducted to characterise four specific groups: a) donors who would donate
      again; b) donors who would not donate again; c) nondonors who would now donate;
      and d) nondonors who still would not donate. RESULTS: Three significant
      discriminant functions emerged discriminating donors from nondonors, those who
      were satisfied with their decision from those who were not, and people who would
      now donate from those who would not. Donation was predicated by formal education,
      being married, volunteerism, signing donor cards, and having personal
      conversations about donation. Subsequent satisfaction was predicted by comfort
      and confidence during the decision-making process, familiarity with medical
      center, and understanding of brain death. A willingness to now donate was
      predicted by personal discussions about donation. CONCLUSIONS: People should be
      encouraged not only to sign donor cards, but to have discussions with family
      about wishes. Individuals should be encouraged to seek the help of family and
      friends during the decision, and be aware of the need of social support from
      family and friends during and after the decision.

PMID- 9560864
TI  - A comparison of related and unrelated marrow donors.
AB  - OBJECTIVE: The purpose of this investigation is to test whether related bone
      marrow donors experience more distress from marrow donation than volunteer
      unrelated donors. METHOD: Participants in the study were 77 related and unrelated
      marrow donors who agreed to complete 11 pre- and 8 postdonation self report
      questionnaires. Related and unrelated donors were recruited from the Bone Marrow
      Transplant Programs at the Brigham and Women's Hospital and the Massachusetts
      General Hospital in Boston, MA. Additional unrelated donors were recruited from
      the American Red Cross-Carolinas and the Heart of America Bone Marrow Donor
      Registry in Kansas City, MO. RESULTS: The 41 unrelated and 36 related marrow
      donors who participated in this prospective study had similar demographic
      backgrounds and predonation questionnaire results, although related donors
      endorsed more items on the Beck Depression Inventory, both before and after
      narrow harvesting. After narrow donation, related donors reported significantly
      more pain than unrelated donors (p = .0001). CONCLUSIONS: It is unlikely that
      intraoperative events alone could account for the increased pain experienced by
      related donors. Related donors were more likely to experience moderate to severe
      physical pain after marrow donation than unrelated donors, on the basis of
      logistic regression analysis (odds ratio = 7.63; 95% confidence interval 2.74,
      23.01).

PMID- 9560865
TI  - Concern about aspects of body image and adjustment to early stage breast cancer.
AB  - OBJECTIVE: Several authors have suggested that patients adjust more poorly to
      breast cancer if they are heavily invested in body image as a source of their
      sense of self-worth. This prospective study examined this possibility, looking at
      two aspects of concern about body image as predictors of several indices of
      adjustment over the first postoperative year. METHODS: At diagnosis (and again a
      year later) 66 women with early stage breast cancer reported how much they valued
      a) a sense of body integrity (or intactness) and b) a good physical appearance.
      The day before surgery, a week afterward, and at 3-month, 6-month, and 12-month
      follow ups, they reported on their mood. At presurgery and at follow ups they
      also rated their attractiveness and sexual desirability and reported on frequency
      of sexual interaction. At follow-ups they also indicated how much their illness
      and treatment were interfering with social and recreational activities. RESULTS:
      Initial investment in appearance was related to distress across the postsurgical
      year. In contrast, investment in appearance made women more resilient against
      deterioration in their perceptions of attractiveness. Concern about body
      integrity did not strongly predict emotional distress, but it related to adverse
      impact on social and recreational activities in the follow-up period, to
      deterioration in feelings of sexual desirability, and to feelings of alienation
      from the self (feeling "not like yourself anymore"). CONCLUSIONS: Body image is
      often thought of in terms of physical appearance, but there is also a body image
      pertaining to integrity, wholeness, and normal functioning. People who are
      greatly concerned about either aspect of their body image are vulnerable to
      poorer psychosocial adjustment when confronting treatment for breast cancer. The
      poorer adjustment takes a different form, however, depending on the nature of the
      patient's body-image concern.

PMID- 9560866
TI  - How multiple types of stressors impact on health.
AB  - OBJECTIVE: Although many studies have focused on the relationship between stress
      and health, few have examined the impact of multiple types of stressors. The
      current study investigated the health impact of four stressors: sexual and
      physical abuse history, lifetime losses and traumas, turmoil in childhood family,
      and recent stressful life events. METHOD: The sample included 239 female patients
      from a referral-based gastroenterology clinic. RESULTS: We found that the four
      stressors (abuse history, lifetime traumas, turmoil in childhood family, and
      recent stressful life events) were related to poor health status (eg, more pain,
      symptoms, bed disability days, physician visits, functional disability, and
      psychological distress); together, these stressors accounted for 32% of the
      variance in overall current health. Furthermore, women who scored high on one
      type of stressor also tended to have experienced other types. Unlike many
      previous studies, we did not find that social support buffered the effects of
      stress. CONCLUSIONS: This study provides evidence that many different types of
      stressors independently contribute to poor health outcome. Such findings suggest
      that health practitioners and researchers should question patients about
      histories of traumatic events, in addition to the examination of the biological
      aspects of illness, inasmuch as both may have notable effects on health status.

PMID- 9560867
TI  - Stressful life events and smoking were associated with Graves' disease in women,
      but not in men.
AB  - OBJECTIVE: Although psychological stress and smoking have been proposed as
      contributing factors to Graves' disease, their independent roles in the
      pathogenesis of this disease have not been determined. We assessed the
      association between Graves' disease and psychological stress and smoking by using
      multivariate analysis. METHODS: By a matched case-control method, we investigated
      the association between Graves' disease and stressful life events, daily hassles,
      smoking, drinking habits, coping skills, and social support in 228 patients (182
      women and 46 men) with newly diagnosed Graves' disease; we used the conditional
      maximum likelihood method. RESULTS: After data were adjusted for daily hassles,
      smoking, drinking habits, social support, and coping skills, we found that
      stressful life events were significantly associated with the risk of Graves'
      disease in women. The relative risk was 7.7 for women with the highest stress
      score compared with women with the lowest stress score (95% confidence interval,
      2.2 to 27, p for trend < .001). Smoking was also independently associated with
      the risk of Graves' disease in women. The relative risk for women with the
      highest number group compared with women with the lowest number group for smoking
      cigarettes was 5.1 (95% confidence interval, 1.0 to 27; p for trend < .001).
      These factors were not significantly associated with Graves' disease in men.
      CONCLUSIONS: Psychological stress and smoking were associated with Graves'
      disease in women, but not in men.

PMID- 9560869
TI  - Obsessionality in anorexia nervosa: the moderating influence of exercise.
AB  - OBJECTIVE: Research has confirmed substantial links between OCD and AN. Not only
      are there psychopathological similarities between the two syndromes, but a marked
      neurochemical correspondence. Extensive exercising is a common feature of AN and
      also has relevance in its links with OCD. There is evidence from the exercise
      induced weight-loss syndrome in animals that exercise and caloric restriction, in
      combination, tend to increase serotonergic activity in a synergistic manner. This
      syndrome has been proposed as a valid model of OCD as well as for AN. To date,
      little research has directly tested this theory in the human condition. METHOD:
      Fifty-three AN patients were categorized as high-level exercisers (N = 22) or
      moderate/nonexercisers (N = 31) based on the frequency of their physical activity
      over the year before assessment. RESULTS: Exercisers scored significantly higher
      on a measure of OC personality characteristics, OC symptomatology, and
      perfectionism--a personality factor associated with the development of Obsessive
      Compulsive Personality Disorder. On the other hand, there were no group
      differences on other salient eating disorder characteristics such as body esteem,
      self-esteem, or weight preoccupation. There were also no differences in degree of
      emaciation as indicated by Body Mass Index. CONCLUSIONS: Findings suggest that
      among AN patients obsessional personality characteristics are linked to high
      level exercising, and that exercising is associated with a greater degree of OC
      symptomatology. Results are discussed in the context of current theories of AN,
      OCD, and some biological mechanisms.

PMID- 9560868
TI  - Cardiovascular reactivity to video game predicts subsequent blood pressure
      increases in young men: The CARDIA study.
AB  - OBJECTIVE: This study was undertaken to determine the relationship between
      heightened reactivity of blood pressure (BP) during stress and 5-year changes in
      blood pressure and hypertensive status, using the CARDIA study. METHOD: A total
      of 3364 participants (910 white men, 909 white women, 678 black men, and 867
      black women), initially 20 to 32 years old and normotensive, were included.
      Cardiovascular reactivity to psychological stressors (video game and star-tracing
      tasks for 3 minutes, cold pressor test for 1 minute) was measured in 1987-1988.
      We then examined reactivity as a predictor of significant BP change (> or = 8 mm
      Hg, thought to represent a clinically significant increase) over the next 5
      years. Logistic regression models were used to control for potential covariates.
      Significant BP change and the development of hypertension (BP greater than 140/90
      or taking medication for hypertension) over the 5-year follow-up were examined in
      separate analyses. RESULTS: Increased systolic blood pressure (SBP) reactivity to
      the video game was associated with a significant 5-year SBP increase among the
      entire cohort, independent of resting SBP (p < .0001). Subsequent analyses showed
      that this relationship held for men but not for women. Reactivity to the star
      tracing task or the cold pressor test did not predict significant BP change.
      Among black men only, new hypertensives (N = 36) had greater diastolic blood
      pressure (DBP) reactivity to the video game (p = .01). CONCLUSIONS: Although BP
      reactivity to all physical and mental stressors used in this study did not
      consistently predict 5-year change in BP in this young cohort, the results
      indicate that reactivity to a video game stressor predicts 5-year change in BP
      and early hypertension among young adult men. These findings are consistent with
      other studies showing the usefulness of stressors producing a primarily beta
      adrenergic response in predicting BP change and hypertension. The results may be
      limited by the shortened initial rest and recovery periods used in the CARDIA
      protocol.

PMID- 9560871
TI  - Changes in cognitive coping skills and social support during cognitive behavioral
      stress management intervention and distress outcomes in symptomatic human
      immunodeficiency virus (HIV)-seropositive gay men.
AB  - OBJECTIVE: We have previously reported decreases in dysphoria, anxiety, and total
      mood disturbance in symptomatic HIV seropositive gay men after a 10-week
      cognitive behavioral stress management (CBSM) group intervention. This structured
      intervention was designed a) to increase cognitive and behavioral coping skills
      related to managing the distress of symptomatic HIV, and b) to increase social
      support among group members. Here we examine the relative contribution of changes
      in coping skills and social support during the intervention period to reductions
      in dysphoria, anxiety, and distress-related symptoms in this sample. METHODS:
      Participants were randomized to a 10-week CBSM group intervention or to a wait
      list control condition. Coping, social supports, and mood were measured before
      and after the intervention period. RESULTS: Members of the CBSM group (N = 22)
      showed significant improvement in cognitive coping strategies involving positive
      reframing and acceptance, and in social supports involving attachment, alliances,
      and guidance at the end of the 10-week CBSM program compared with controls (N =
      18) who showed decrements in these coping abilities and no changes in social
      support. Improved cognitive coping, specifically acceptance of the HIV infection,
      was strongly related to lower dysphoria, anxiety, and total mood disturbance in
      both conditions. Changes in social support and in cognitive coping skills seem to
      mediate the effects of the experimental condition on the changes in distress
      noted during the intervention. CONCLUSIONS: These results suggest that cognitive
      coping and social support factors can be modified by psychosocial interventions
      and may be important determinants of the changes in psychological well-being and
      quality of life during symptomatic HIV infection that can be achieved through
      this form of intervention.

PMID- 9560870
TI  - Elevated levels of psychophysiological arousal and cortisol in patients with
      somatization syndrome.
AB  - OBJECTIVE: This study investigates psychological and psychobiological processes
      in patients with somatization syndrome. METHOD: We compared physiological
      measures (heart rate, finger pulse volume, electrodermal activity,
      electromyography), cortisol levels, and subjective well-being during rest and
      during a mental stress task as well as selective attention and memory for illness
      related words in 58 patients with somatization syndrome and 21 healthy controls.
      RESULTS: The somatization group had higher morning salivary cortisol
      concentrations, higher heart rates, and lower levels of finger pulse volume.
      During the mental stress task, patients with somatization syndrome felt more
      distressed and had higher heart rates, whereas controls showed habituation to the
      experimental situation. We were unable to demonstrate an attention or memory bias
      specific for somatization. CONCLUSIONS: The results point to several
      psychological, psychophysiological, and psychobiological mechanisms that might be
      involved in the maintenance of somatization syndrome. These results are discussed
      from a cognitive-psychobiological perspective.

PMID- 9560872
TI  - Depressive symptoms as an underlying factor of the sensation of dry mouth.
AB  - OBJECTIVE: The purpose of this survey was to study the sensation of oral dryness
      and its underlying factors in the 55-year-old population of Oulu (a medium-sized
      Finnish town), 780 of whom (77%) participated. METHOD: In addition to the
      examination of oral health status and salivary flow rate measurements, depressive
      symptoms were determined on the basis of the Zung Self-Rating Depression Scale
      (ZSDS). The participants were also interviewed about their health, medication,
      physical health, physical activity, smoking habits, alcohol consumption, and
      factors related to their work. RESULTS: The prevalence of subjective sensations
      of dry mouth was 25.8% among men and 33.3% among women (p = 0.025). A
      statistically significant association was found between a subjective sensation of
      dry mouth and a low unstimulated flow rate, regular smoking, xerogenic
      medication, and the presence of at least one illness connected with dry mouth.
      Those who had a sensation of dry mouth also thought their physical condition and
      their health to be poorer and more often had a high rate of depressive symptoms.
      After the confounding factors had been added stepwise into the logistic
      regression model, depressive symptoms were still significantly associated with
      the sensation of oral dryness. CONCLUSIONS: When evaluating the causes of the
      sensation of dry mouth, the possibility of depression as an underlying factor
      should be considered.

PMID- 9560873
TI  - Cardiovascular, endocrine, and receptor measures as related to sex and menstrual
      cycle phase.
AB  - OBJECTIVE: The present study was undertaken to elucidate possible mechanisms
      underlying sex differences in cardiovascular measures or reactivity to challenge.
      Because there is vastly diverging literature on the issue, we tried to control
      for endocrine and psychological factors, which might contribute to some of the
      apparent discrepancies. METHODS: Blood pressure, heart rate, adrenaline, and
      noradrenaline in women (N = 24) and men (N = 14) were examined during baseline
      and challenge (Stroop Test and Cold Face Test). Adrenoceptor density on
      lymphocytes (beta 2) and platelets (alpha 2) were determined to examine possible
      sex differences in underlying cardiovascular mechanisms. Gender effects were
      controlled by assessing gender role orientation and task appraisal. Women were
      tested during either the follicular (N = 12) or the luteal (N = 12) phase of the
      menstrual cycle (verified by estradiol, progesterone, and luteinizing hormone).
      RESULTS: Follicular and luteal phase women did not differ in any parameter except
      progesterone. We observed sex-related differences in absolute levels of
      physiological parameters, the male group having higher systolic blood pressure
      levels, higher adrenaline plasma concentrations, and significantly more alpha 2
      adrenergic receptors. Both challenges elicited pronounced cardiovascular and
      endocrine responses. Men and women did not differ in response magnitude, in task
      appraisal, or gender role orientation. CONCLUSIONS: The assumption that female
      sex hormones reduce reactivity to challenge is not supported by our data. The
      frequently reported male/female differences in reactivity may be caused by an
      interaction of gender and task characteristics.

PMID- 9560874
TI  - Endogenous opioids inhibit ambulatory blood pressure during naturally occurring
      stress.
AB  - OBJECTIVE: Laboratory experiments suggest that endogenous opioids inhibit blood
      pressure responses during psychological stress. Moreover, there seem to be
      considerable individual differences in the efficacy of opioid blood pressure
      inhibition, and these differences may be involved in the expression of risk for
      cardiovascular disease. To further evaluate the possible role of opioid
      mechanisms in cardiovascular control, the present study sought to document the
      effects of the long-lasting oral opioid antagonist naltrexone (ReVia, DuPont,
      Wilmington, DE) on ambulatory blood pressure responses during naturally occurring
      stress. METHOD: Thirty male volunteers participated in a laboratory stress study
      using naltrexone followed by ambulatory blood pressure under placebo and during
      the subsequent 24-hour period. Within-subject analyses were performed on
      ambulatory blood pressures under placebo and naltrexone conditions. RESULTS:
      Laboratory results indicate no significant group effects of naltrexone on blood
      pressure levels or reactivity. Ambulatory results indicate that during periods of
      low self-reported stress, no effect of opioid blockade was apparent. In contrast,
      during periods of high stress, opioid blockade increased ambulatory blood
      pressure. CONCLUSIONS: These findings suggest that naltrexone-sensitive opioid
      mechanisms inhibit ambulatory blood pressure responses during naturally occurring
      stress.

PMID- 9560875
TI  - Laterality in somatization.

PMID- 9560876
TI  - Evolution of pathology practice in the United States: current status and future
      trends.
AB  - This article traces the development of pathology practice from its origins in
      autopsy pathology to its current practice in the United States. The American
      model of practice differs markedly from that in continental European countries
      because of the extensive incorporation of "Clinical Pathology" with the
      traditional disciplines of anatomic pathology under the auspices of the Pathology
      Department. "Clinical Pathology" as it is now defined includes the laboratory
      testing disciplines of Chemistry, Hematology, Immunology, Medical Microbiology,
      and Transfusion Medicine. The increasing importance of computers and information
      management, DNA diagnostic techniques, and the multiple roles of the pathologist
      as a researcher and consultant in pathology practice in the United States is
      discussed.

PMID- 9560877
TI  - [Fetal pathology in Fabry's disease and mucopolysaccharidosis type I].
AB  - Fetal Fabry disease (defect of alfa galactosidase) and mucopolysaccharidosis I
      (defect of alfa iduronidase, family with IH phenotype) were diagnosed by
      biochemistry in two risk gravidities subsequently interrupted according to
      mother's demand. Fetus with Fabry disease (gestation age 19 weeks) had
      rudimentary storage in kidney and myenteric plexuses cells, cardiocytes were
      normal. Biopsy of chorionic villi showed a bit more conspicuous storage in single
      trophoblastic elements. Much more striking storage was observed in MPS I
      (gestational age 14-15 weeks) especially in liver (hepatocytes and sinus cells),
      spleen (sinus endothelial cells and pulp macrophages) and fibroblasts of skin and
      placenta. Skin peripheral nerves and cerebral cortical gangliocytes did not show
      any lysosomal storage. Different manifestation of storage in fetal age may reflex
      the speed of lysosomal storage development in both lysosomal enzymopathies.

PMID- 9560878
TI  - [The effect of two beta-2 sympathomimetic bronchospasmolytics on the ratio of
      sialylated and sulfated glycoconjugates in goblet cell secretions of the tracheal
      epithelium].
AB  - Rabbits were made to inhale two different beta 2 sympathomimetic
      bronchospasmolytics-salbutamol in Ventolin and phenoterolhydrobromid in Berotec.
      Changes of secretion contents in tracheal goblet cells were evaluated by
      classical and lectin histochemistry 30 minutes after administration of drugs.
      When comparing with control rabbits Ventolin completely suppressed the secretion
      of neutral glycoconjugates for the benefit of acidic glycoconjugates and
      completely suppressed sialylation. The administration of Berotec suppressed
      neutral glycoconjugates, either, but the suppression of sialylation was
      uncomplete. Berotec was found a less damaging agent.

PMID- 9560879
TI  - [Desmoplastic fibroblastoma].
AB  - We report a light microscopic and ultrastructural appearance, and
      immunohistochemical profile of two benign tumours of soft tissue recently
      designated as desmoplastic fibroblastoma (collagenous fibroma). The tumours were
      located in the foot and well demarcated. Microscopically, they were composed of
      stellate--or spindle--shaped cells embedded in a hypovascular fibrous of
      fibromyxoid stroma. Immunohistochemical examination showed that tumours were
      diffusely positive for vimentin and focaly positive for smooth muscle actin and
      muscle specific actin. Ultrastructurally, the neoplastic cells had features of
      fibroblasts and myofibroblasts.

PMID- 9560880
TI  - [Synovial metaplasia around breast implants].
AB  - Three cases of the periprosthetic breast capsules showing typical features of
      synovial metaplasia are presented. The histological picture is characterized by
      the presence of cellular layer mimicking synovial membrane. These elements are
      devoid of basement membrane, otherwise, nevertheless, they strongly resemble
      single- or multilayered epithelium. Focally, the differentiation towards giant
      multinucleated cells is noted. Immunohistochemical profile, as well as the
      ultrastructure of the cells, confirms their histiocytic origin with advanced
      differentiation towards elements of the synovial membrane. These histological
      features are referred to as synovial or synovial-like metaplasia. They are found
      in considerable fraction of textured breast implant capsules. The pathogenesis
      remains uncertain; however, similar picture was observed in other locations in
      association with prolonged or repeated action of mechanical forces. Thus,
      movement of the implant in situ is the most probable trigger of synovial
      metaplasia.

PMID- 9560881
TI  - [DNA image cytometry in urothelial carcinomas. A pilot study of a new application
      module of the Lucia G DNA analysis system].
AB  - OBJECTIVE: To introduce and test a standardized measurement protocol for DNA
      image cytometry into a newly developed LUCIA G system application program.
      Contribution to a discussion concerning the possibility of using the histology
      sections for DNA image cytometry. STUDY DESIGN: Routine biopsy material from 18
      urinary bladder cancer cases was analyzed (Grade 1: n = 6, Grade 2: n = 6, Grade
      3: n = 6), both in histological and in cytoseparated preparations. More than one
      hundred diagnostic and more than 30 reference cells were measured. DNA features
      (mean DNA value, 2cDI, Bocking's grade of malignancy) and histogram types in
      Auer's classification (AI-IV) were compared. RESULTS: Most carcinomas measured
      were aneuploid (two thirds G1, all G2, G3). The most common histogram type was A
      IV. Malignancy grade was mostly slightly higher in cytoseparated material, the
      shape of the histogram was analogous. Two carcinomas looking euploid in histology
      sections were proven aneuploid in cytoseparation. CONCLUSION: More convenient
      tissue section measurement provided useful DNA profile information in most cases.
      Those without proven aneuploidy should be additionally measured in
      cytoseparations. An experienced pathologist meeting strictly measurement protocol
      demands is an important part of the measurement system.

PMID- 9560882
TI  - [Detection of point mutations on the Ki-ras gene using the PCR technique].
AB  - Present study was undertaken to detect Ki-ras point mutation at codon 12 in
      pancreatic adenocarcinomas (CaP) using the polymerase chain reaction-restriction
      fragment lengths polymorphism (PCR-RFLP). Three modifications of PCR-RFLP were
      performed with a mismatched primers creating a recognition site with only one
      allelic from (wild or mutated). Using two-step PCR-RFLP and two modifications of
      one-step PCR-RFLP we examined 5 resected adenocarcinomas of pancreas, 6
      pancreatic juices and one DNA sample from peripheral blood of patient with
      generalized stadium of CaP. We compare all techniques and conclude, that the very
      sensitive two step PCR-RFLP is a suitable method for detection point mutations
      and eliminates the need for either oligonucleotide hybridization or DNA
      sequencing.

PMID- 9560883
TI  - [Detection of lorazepam and lormetazepam metabolites in urine using thin-layer
      chromatography].
AB  - The determination of benzodiazepine derivatives lorazepam and lormetazepam in
      urine is based on detection of their metabolites 2-amino-2',5
      dichlorobenzophenone and 2-methylamino-2'5-dichlorbenzophenone in hydrolyzed
      urine. Both substances are structurally very similar to the metabolites of
      diazepam 2-amino-5-chlorbenzophenone and 2-methylamino-5-chlorbenzophenone and
      their mobility on thin layer chromatograms is similar as well. This could cause
      their confusion and misinterpretation of the results. Therefore suitable
      combination of mobile phases and thin layer plates was sought in this study for
      the unambiguous identification of respective benzophenones by thin layer
      chromatography.

PMID- 9560884
TI  - [The concept of forensic medicine].

PMID- 9560886
TI  - [Present knowledge of human spleen function].
AB  - The human spleen is an important lymphoid organ participating in immune reactions
      against all types of circulating antigens. It also removes particles of
      nonantigenic nature from blood circulation. The structure of the spleen,
      containing specialized cells types, provides a microenvironment where various
      intercellular interactions occur and determines the course of development of
      immune and nonimmune reactions. Though the spleen significantly participates in
      host defense reactions it is not inevitable for life. However, removing of the
      spleen increases the risk of overwhelming infections by bacteria with
      polysaccharide capsules.

PMID- 9560887
TI  - [The spleen in hereditary spherocytosis].
AB  - Hereditary spherocytosis is the most common inherent, autosomal dominant
      hemolytic anemia. Mild splenomegaly, venostasis and common decrease of while pulp
      is characteristic for hereditary spherocytosis. Cords are filled with
      spherocytes, sinuses can be empty or squeezed. Both sinuses and veins include
      ghost erythrocytes that lost haemoglobin. They are seen light-microscopically in
      differential interferent contrast. Macrophages are numerous, sinus lining cells
      are hypertrophic. Erythrophagocytosis is hardly seen by electron microscope. Not
      all red blood cells are spherocytes. Spherocytes are seen well in
      electronmicroscopy. We did not observed transition of erythrocytes through sinus
      walls. In certain circumstances lots of ferritin is seen both intra and
      extracytoplasmically. Iron accumulation in cords can result in their fibrosis.

PMID- 9560888
TI  - [Chronic autoimmune thrombocytopenia in the spleen and microparticles as seen in
      scanning electron microscopy].
AB  - In chronic autoimmune thrombocytopenia numerous round formations in the sinus
      lining cells are observed by scanning electron microscopy. They occur sometimes
      on the surface of erythrocytes passing through the sinus wall. It is possible
      that they are not cytoplasmic processes but platelet microparticles sticking on
      the surfaces of various cells. These particles are too small in routine counting
      of blood platelets in the light microscopy and probably too fragile in examining
      in transmission electron microscopy.

PMID- 9560889
TI  - [Fibronectin and the human spleen].
AB  - Fibronectins are glycoproteins with a function of molecular glue. The aim of the
      study is to encourage interest in processes in extracellular matrix of the
      spleen. Undigested cryostat or formol-paraffin sections and commercially
      available antibodies were used. We were mostly successful in extracellular
      localization of fibronectin in trabeculae, vessel walls and lamellae of
      circumferent reticulum of periarterial lymphatic sheaths and in the ring fibres
      of the sinuses. Changes in the amount of fibronectin occurred, for example, in
      circulation disturbances. In hereditary spherocytosis the ring fibres were
      reduced. Increase of fibronectin can suggest the development of fibrosis.

PMID- 9560890
TI  - [Reactivity of antibodies to collagen types I to IV and antibodies to chondroitin
      sulfate in the spleen].
AB  - Antibodies to collagen type I and III reacted negatively, antibodies to collagen
      type IV positively with reticulin, trabeculae and circumferent reticulum of
      lymphatic sheaths, poorly positively with capsula, strongly positively with
      subcapsular zone. Antibodies to collagen type II reacted positively with capsula,
      poorly with subcapsular zone, strongly with sinus wall and poorly with
      trabeculae. They did not react with circumferent reticulum of periarterial
      lymphoid sheaths. Antibodies to collagen type II and IV reacted positively with
      central arteries. Antibodies to chondroitinsulphate C reacted poorly and
      antibodies to chondroitinsulphate B strongly positively with sinus walls and oval
      cells spread in the white and red pulpa. Antibodies to chondroitin sulphate A
      reacted similarly as antibodies to chondroitinsulphate B.

PMID- 9560891
TI  - [Morphometric analysis of the spleen].
AB  - Present possibilities of morphometric analysis of the spleen have been studied.
      We have compared possibilities provided by stereological calculation and by
      computer image analysators a) Telemet II (Tesla, Piestany) and b) CUE-2 GALAI
      (Israel). In both latter cases equidensitometric evaluation and image processing
      methods were used. Stereological calculations are not technically demanding but
      time consuming. Computer image processing on the base of equidensitometric
      measurements is more effective that stereological calculations. The difference
      between used equipments is based on access to appropriate microscopic and
      computer technique and software equipment.

PMID- 9560892
TI  - [Traumatic rupture of the spleen. Histopathologic findings].
AB  - The most common causes of splenic rupture are blunt injury and surgical
      intervention in abdominal cavity. Morphological investigation of the spleen often
      shows but a small capsular laceration as well as haemorrhage and granulocytic
      infiltration in microscopy of its margins. The laceration may be sometimes
      difficult to find. There are two types of microscopical haemorrhage. One in sinus
      lacking subcapsular tissue zone, the other in deeper layers. In this case the
      tissue haemorrhage is diffuse, sometimes within or around the marginal zone. The
      sinuses are neither collapsed nor obturated by any material even close to margins
      of the wound.

PMID- 9560893
TI  - [Dermoid cyst of the spleen].
AB  - The case report of a 14-year old girl is given. In her spleen of the weight of
      1580 g an irregular cyst of glossy inner surface and with striking trabeculation
      developed. It was filled with clear greenish liquid. The wall was formed by
      hyalinised collagen tissue which was covered by epidermoid and cuboidal
      epithelium on the inner surface. Vessel conglomerates were frequent, some
      bleeding or mononuclear infiltrates, foci of giant cell granulation tissue,
      lymphoid or fatty tissue were present.

PMID- 9560894
TI  - [Technical problems in the preparation of biopsy samples of the spleen].
AB  - Spleen tissue sampling for bioptical examination should be performed after mutual
      consultation of clinician and pathologist. Clinician should know what is expected
      from the pathologist. This can influence preparation and sampling method
      considerably. In a great amount of cases the whole organ is removed. A lab
      technician is sampling on her own and her contribution to a good result can be
      either positive or negative. Imprint preparations from the tissue sections can be
      useful. Specialized examination should be performed in the presence of a
      pathologist or his co-workers. The active approach of a lab technician can
      significantly contribute to the value of examined sample of the spleen, of the
      organ until recently considered to be not important or full of mysteries.

PMID- 9560895
TI  - Brown adipose tissue. I. Morphology. (Review).
AB  - Brown adipose tissue appeared in mammals with the development of homeothermy. In
      consequence of this, their organism became able to maintain constant body
      temperature independent on the thermal conditions of the surroundings. This
      tissue-contrary to the white adipose tissue-is distributed only in certain
      restricted portions of the body. The paper deals with actual literary data of
      morphology and function of brown adipose tissue.

PMID- 9560896
TI  - Brown adipose tissue. II. Effect of pathologic and environmental conditions
      (Review).
AB  - Brown adipose tissue is an important source of non-shivering thermogenesis. Its
      metabolic activity and development are regulated by adrenalin secretion. The
      greatest amount of brown adipose tissue in humans was observed during the first
      decade of life. Later it disappears from many sites, but is preserved in the neck
      and around the kidneys and the adrenal glands. Increased amounts of brown adipose
      tissue have been reported to occur in association with certain situations and
      diseases. A review of these literary data is presented.

PMID- 9560898
TI  - [Homicide and mutilation of the body--review of the literature].
AB  - In two hitherto not elucidated murders of two young women the bodies were
      devastated in a peculiar way and some organs were removed. The author presents a
      review of literature focused on manipulation with the human body and also with
      regard to the ability to commit such operations.

PMID- 9560899
TI  - [Drowning--characteristic signs and calculation of their diagnostic value].
AB  - In a group of 387 drowned subject and 50 controls typical signs of drowning were
      investigated. Paltaufs spots, aqueous emphysema of the lungs, liquid in the
      stomach, significant drop of chlorides, creatinine and urea in the left heart and
      presence of liquid in the paranasal sinuses. The author investigated the
      frequency of these signs and by comparison of data of these signs in the two
      groups the diagnostic importance of different diagnostic signs was calculated.

PMID- 9560901
TI  - [Sinus histiocytosis with massive lymphadenopathy--a disseminated form of the
      Rosai-Dorfman syndrome].
AB  - A 20 year-old black male presented with a generalized lymphadenopathy, skin
      papules with maximum involvement of the head and trunk region, and elevated
      temperature. Ultrasound, CT and bone scans revealed infiltration of the kidneys
      and bones. Surgical specimens of the cervical lymph nodes showed massive
      infiltration of sinuses by histiocytes with engulfed lymphocytes and granulocytes
      in their cytoplasm. A similar finding was found in the excised dermis and
      nasopharyngeal mucosa. Immunohistochemical investigations showed a strong
      positive reaction of sinusoidal macrophages with anti S100 protein, anti alpha-1
      antitrypsin and alpha-1 antichymotrypsin antibodies, negative CD1a. The engulfed
      granulocytes were positive with lysozyme and MAC387 antibodies; lymphocytes
      reacted with antilymphocytic antibodies L26, HLADR, UCHL-1 and OPD4 only rarely,
      possibly due to alterations of their cell membranes in the cytoplasmic
      environment of histiocytes. Occasional plasma cells were also entrapped in the
      macrophages. The best results were obtained with CD3 antibody which showed focal
      predominance of phagocytosed T cells. These findings confirm a nonselective
      nature of the emperipolesis. In situ hybridization with probes EBER and BHLF
      against Epstein-Barr virus sequences was negative. The pacient was treated by
      multidrug chemotherapy with a moderate regression of the infiltrates. The
      symptoms of the disease persisted for 10 months from the treatment start but
      further course of the disease is uncertain. The patients is lost to follow up.

PMID- 9560902
TI  - [Typing of malignant mantle zone lymphomas].
AB  - Principles derived from a group of 46 ML of the mantle zone are presented: Mantle
      pattern of a ML and its cytological structure are mostly sufficient for positive
      basic diagnosis. Diffuse mantle zone ML need detection of BCL-1 and CD5
      hyperexpression which are characteristic for small-cell and centrocytoid forms
      when compared with BCL-2 positive centrofollicular lymphomas. B monocytoid
      lymphomas from the parafollicular subgroup as well as plasmacytoid ML from the
      marginal subgroup retain faint BCL-1 positivity but lose CD5 positivity. That may
      results in attempt of problematic narrowing of mantle zone definition because of
      existence of the mixed cellularity forms of mantle zone ML. Nodular mantle zone
      ML are clinically recognized late and are unsensitive to treatment which is
      opposite to the original idea of their relative benignity. M-coding of mantle
      zone ML is very defective because the codes do not separate nodular
      (perifollicular) and diffuse variants.

PMID- 9560903
TI  - [PCR analysis of DNA in paraffin sections of malignant lymphomas].
AB  - The polymerase chain reaction was used to detect the clonal rearrangement of
      immunoglobulin heavy chain gene in paraffin embedded samples of human lymph
      nodes. We developed a sensitive and reliable method of the DNA isolation from 4-5
      tissue sections, which enabled us to perform 50-100 PCR reactions. We compared
      the reactive lymph nodes and non-Hodgkin's malignant lymphomas using framework 3
      and J region primers. PCR products were examined by agarose gel electrophoresis.
      The dominant 80-120 bp amplification product was found in all lymphoma samples.
      The samples of reactive nodes were negative.

PMID- 9560904
TI  - [Visceral and cutaneous leishmaniasis].
AB  - Two cases of kala azar and 5 cases of cutaneous leishmaniasis were found in
      bioptic files from previous 50 years in Hlava Institute of Pathology in Prague, 4
      of them were cumulated in 1994 and 1995. All cases followed short stays in
      Mediterranean or Caribbean area. The latest kala azar was identified from bone
      marrow trephine biopsy and subsequently, leishmanias were also found in an
      inapparent hepatopathy. In cutaneous cases, a fibrinoid vasculitis was observed
      in addition to accumulation of leishmanias laden macrophages and tuberculoid
      granulomas.

PMID- 9560905
TI  - Medulloepithelioma in a cat.
AB  - Castrated male of European cat, bastard, 16 month-old suffered from a grayish
      pink tumour in the anterior chamber of the right eyeball in the course of last
      six months. After enucleation, the eye was examined by histology,
      immunohistochemistry (NSE, NPF, S-100 protein) and electronmicroscopy. The tumour
      was classified as malignant medulloepithelioma. Existence of neuroblastoma in
      animals and frequency of neuroblastoma and medulloepithelioma in humans and
      animals is discussed.

PMID- 9560906
TI  - [Tumors in wildlife].
AB  - Wild animal tumours have not been much studied yet. Authors found six mostly
      benign cases in Czech Republic in checking hunts between the years 1988 and 1993:
      Mature differentiated ovarian teratoma and apocrine skin adenoma in field hare,
      intraductal mammary papillomatosis in a roe, complex odontoma and pleomorphic
      mammary carcinoma (single malignancy in the group) in fox. A soft tissue tumour
      in a fallow-buck's neck could not be histogenetically classified. A high
      structural equivalence of animal and human tumours allows using ICD-O
      classification as a whole.

PMID- 9560907
TI  - [Anniversary of the International Academy of Pathology].

PMID- 9560908
TI  - [Complications in catheterization of the subclavian vein].
AB  - The authors of the article inform about the complications of the infraclavicular
      subclavian vein catheterization, enclosing some practical cases. They suggest the
      applicable steps that should be taken in case of the death due to the
      catheterization not only for pathologists but also for the regular clinical
      staff.

PMID- 9560909
TI  - [Evaluation of the vital reaction in injuries].
AB  - Evidence of an early vital reaction after a skin injury is sometimes of decisive
      importance in forensic practice. Attention is devoted increasingly to
      immunohistochemical evidence of substances, the presence of which in the borders
      of the wounds signalizes an intravital origin of the injury. In this context
      evidence was focused on detection of glycophorine at sites of haematomas of the
      skin and subcutaneous layer and to fibronection in the borders of injuries and in
      haematomas. To visualize the two substances in paraffin tissue sections, the
      immunohistochemical method of indirect immunoperoxidase reaction was selected
      where in the first layer specific sera were used wither against glycophorine A, B
      or against fibronectin. Glycophorine is a sialoglycoprotein which is part of the
      red cell membrane. It can be detected at the site of haematomas and after the
      disintegration of erythrocytes during post-mortem autolysis. Conversely it is
      lacking where membrane structures were not present. This makes it possible even
      during advanced stages of post-mortem changes to differentiate actual haematomas
      from mere post-mortem inhibition of tissue by blood pigment (e.g. in hypostasis)
      where glycophorine cannot be detected. Fibronectin, another glycoprotein
      substance can, already in the early stage of injury, form the basis for a netlike
      structure in the shape of fine "strings". Detection of fibronectin suggests the
      intravital development of injury and in the authors cases it could be detected
      already within several minutes after the development of the injury.

PMID- 9560910
TI  - Brown adipose tissue. III. Effect of ethanol, nicotine and caffeine exposure.
AB  - Brown adipose tissue is known to be the most important organ for generating heat
      in non-shivering thermogenesis. Process of thermogenesis and thermoregulation may
      be affected by many drugs. The paper deals with actual literary data of effect of
      ethanol, nicotine and caffeine on brown adipose tissue, heat production and its
      regulation in experimental animals and in human.

PMID- 9560912
TI  - [Antiphospholipid syndrome and spontaneous abortions].

PMID- 9560913
TI  - [Drug interaction and oral contraception].

PMID- 9560914
TI  - [How to prescribe and interprete obstetric ultrasonography].

PMID- 9560915
TI  - [Preimplantation genetic diagnosis].

PMID- 9560916
TI  - [Chlamydia trachomatis: should it be systematically be screened or treated?
      Literature review and cost/benefit estimation in France].
AB  - Chlamydia trachomatis is a primary cause of acute or silent salpingitis leading
      to infertility and ectopic pregnancy. The C. trachomatis epidemic, undiscovered
      in most cases, spreads, mostly in adolescents, during the years following the
      onset of sexual activity. As opposed to gonococcal infection which has greatly
      decreased, C. trachomatis cervical and urethral infection is commun in young
      occidentals. More then 30 different studies covering 200-12000 subjects screened
      in family planning centers, college women and men, students and military recruits
      in different parts of the USA, in Scandinavian countries and France, indicate a
      prevalence of 5-20% (mean 10%) in apparently healthy young females < 25 years and
      5-10% in males. Female prevalence is strongly related to age, being highest (5
      20%) in women < 20 years old. Several cost-benefit analysis show that the total
      cost of the general screening in young populations, which can easily be carried
      out for women in family planning centers, could save twice the cost of treatment
      for pelvic inflammatory disease caused by C. trachomatis and six times the total
      cost of C. trachomatis epidemics if late sequelae are taken into account (tubal
      infertility treatment, ectopic pregnancy). In France, screening should save 12 to
      48 millions French francs each year, depending of the cost of detection. The
      final benefit of detection should be the eradication of the epidemic as obtained
      to date in Scandinavian countries.

PMID- 9560917
TI  - [Mixed endoscopic colposuspension (retroperitoneal and vaginal) for the treatment
      of female stress urinary incontinence: technique and preliminary results].
AB  - Preliminary results of a mixed technique of cervical bladder suspension by
      retroperitoneal laparoscopy and vaginal route. 35 patients, average age 55 years
      with stress incontinence. Every patients had positive Bonney test. Associated
      lesions were prolapse (72%). In this retrospective study, we give technique in
      details. Average operative time: 65 minutes. Average hospital stay: 5.4 days.
      Success rate: 89%. Retzius hematoma were treated by laparoscopy. Average lapse of
      time: 10.5 months. Interesting technique in associated prolapse.

PMID- 9560918
TI  - [Emergency obstetrical hysterectomy].
AB  - Hysterectomy on pregnant uterus is a mutilating procedure used by obstetrician
      only when he haven't choice in case of major complications of pregnancy or
      delivery. This retrospective study worked on 35 cases of obstetrical hysterectomy
      performed on 22 months period (January 94-October 95). The frequency of the
      procedure among all the in hospital deliveries was 0.45%. The mean age of the
      patients was 31 years, and the mean parity was 7. 77.5% of the women were
      referred from over surrounding hospitals where natural deliveries had failed. We
      performed the hysterectomy because of uncontrolled haemorrhage in 71.7%, and
      infection in 25.8%. Sub-total hysterectomy was performed in 82.8%. Maternal
      mortality was 20%. Hysterectomy is very mutilating, but is a life rescueing
      procedure behind a lifethreatening complication of pregnancy or delivery. The
      best strategy to prevent the necessity of hysterectomy, is to develop the early
      obstetrical reference program that unfortunately is not yet in practice in our
      health care system.

PMID- 9560919
TI  - [Ureteral endometriosis: three cases. Diagnostic and therapeutic management.
      Literature review].
AB  - Ureteral endometriosis is a rare but serious entity because of its insidious
      evolution which can lead to the loss of kidney function. Three cases are
      reported: two patients have received a medical and endoscopic management and the
      third one has undergone a surgical procedure. According to the literature, the
      authors suggest a diagnostic and therapeutic tree.

PMID- 9560920
TI  - [Screening high-risk pregnancies].

PMID- 9560921
TI  - [Birth control practices in Morocco. 200 laparoscopic Yoon ring tubal ligations].

PMID- 9560922
TI  - [Treatment of sexually transmitted diseases and pelvic infections in gynecology].

PMID- 9560923
TI  - [Fusarium toxins in grain: results of monitoring].

PMID- 9560924
TI  - [Hygienic certification of registering of biologically active food additives].

PMID- 9560925
TI  - [Occupational hygiene and physiology of miners extracting multimetal ore in the
      Far North].

PMID- 9560926
TI  - [Problems of occupational diseases in workers of nickel-cobalt industry].

PMID- 9560927
TI  - [Evaluation of preclinical signs due to exposure of workers to static magnetic
      fields].

PMID- 9560928
TI  - [Clinico-immunological characteristics of the state of upper airways in workers
      engaged in plasma technology].

PMID- 9560929
TI  - [Hygienic problems in the use of industrial waste in various branches of national
      economy].

PMID- 9560930
TI  - [Sanitary legislation: history, ways of improvement].

PMID- 9560932
TI  - [Problems of sanitary-epidemiological services in the Stavropol territory under
      present conditions].

PMID- 9560931
TI  - [Organizational, legal, methodical provisions and planning of the state sanitary
      epidemiological services in emergency situations].

PMID- 9560933
TI  - [Improvement of the state sanitary and epidemiological surveillance: experience
      and goals].

PMID- 9560934
TI  - [Experience in inspecting low-output food production industries].

PMID- 9560935
TI  - [Problems in assessing carcinogenic risk of exposure to chemical pollution of the
      environment].
AB  - The main stages of and principles of methodology of assessment of a carcinogenic
      risk from exposure to environmental factors are considered. The carcinogenic
      risks of exposure to MAC of in the ambient air of the populated areas, in the
      reservoir water, and in the air of a working zone were calculated by using the
      carcinogenic potential. Analyzing the data obtained has indicated that a great
      variety of potential carcinogens presents a high risk even if the hygienic
      standards approved now are followed. The methodological and organization aspects
      of the use of the procedure for assessing carcinogenic risks in Russia are
      discussed.

PMID- 9560936
TI  - [Health status of residents of ecologically unsound urban areas].

PMID- 9560937
TI  - [Hygienic assessment of alkaline coagulants and zeolites in obtaining drinking
      water].

PMID- 9560938
TI  - [Health status of workers engaged in metallurgy industry].

PMID- 9560939
TI  - [Quality of agricultural crops from lands irrigated with purified sewage].
AB  - Anionic surfactants (AS) not only can move from the soil to cereals, but can
      increase the translocation of some toxic agents (lead, copper, zinc). The
      tolerable anionic AS in the irrigation of soddy podzolic soils is 12 kg/ha.

PMID- 9560940
TI  - [Features of physical and sexual development of school children at different-type
      schools].
AB  - The results of examination of 932 schoolchildren who study at school of different
      types are presented. They show that the physical and sexual developments of
      children depend on the type of school. Harmonious development is observed in
      Lyceum schoolchildren while dysharmonious one is more common in children from
      general educational schools. Physical development is associated with
      socioeconomic and ethnic factors.

PMID- 9560941
TI  - [Characteristics of the radio-ecologic situation in the area of Totsk nuclear
      explosion and the immune status of schoolchildren residing in the vicinity].
AB  - Environmental pollution caused by radioactive and non-radioactive chemicals, and
      the immunity of schoolchildren who reside in the area exposed to the Totsk
      nuclear explosion (1954) are comparatively analyzed. The results indicate that
      the area under study has higher levels of 137Cs than that of a control area.
      There were immunological changes in children, which are obviously associated with
      the nuclear explosion.

PMID- 9560942
TI  - [Use of ultraviolet irradiation in the prevention of ecologically-induced immune
      diseases].

PMID- 9560943
TI  - [Characteristics of modifying effects of formaldehyde on carcinogenesis].

PMID- 9560944
TI  - [Evaluation of the quality of activities of state sanitary and epidemiological
      surveillance subdivisions under present-day conditions].

PMID- 9560945
TI  - [Comparative characteristics of research methods in congenital disorders of color
      vision].

PMID- 9560946
TI  - ["Information ecology" snd human health under present-day conditions].

PMID- 9560947
TI  - Mitochondrial disorders.
AB  - In this minireview, we attempt to survey the three main group of mitochondrial
      disorders, defects of nuclear DNA, defects of mitochondrial DNA, and defects of
      intergenomic signaling, with emphasis on recent contributions and pathogenetic
      mechanisms. In so doing, we have tried to point out some of the numerous unsolved
      problems in genotype/phenotype correlation and to indicate future directions of
      research.

PMID- 9560948
TI  - PCR-based genotyping of MNSs blood group: subtyping of M allele to MG and MT.
AB  - PCR-based genotyping of MNSs blood group system was investigated in combination
      with restriction fragment length polymorphism (RFLP), single-stand conformation
      polymorphism (SSCP) and allele-specific PCR amplification (ASPA) techniques. M
      and N alleles are based on three nucleotide substitutions in exon 2 and one base
      change (G or T) in an intron of glycophorin A locus. The latter single base
      change was also found among M alleles analyzed in this study, so that M allele
      appeared to be subdivided into MG and MT. All three alleles, MG, MT and N were
      identified clearly by RFLP or SSCP analysis following a single amplification. S
      and s alleles are based on one nucleotide substitution in exon 3 of glycophorin B
      gene. Genotyping of Ss blood group system was also explored by PCR-SSCP or ASPA
      analysis, and problems in the methods were discussed.

PMID- 9560949
TI  - DNA-based prenatal diagnosis of a Korean family with tyrosinase-related
      oculocutaneous albinism (OCA1).
AB  - Tyrosinase-related oculocutaneous albinism (OCA1), an autosomal recessive inborn
      error of pigmentation, is caused by the deficiency of tyrosinase. We had
      previously identified two different mutations of the TYR gene in a four year old
      Korean male with mild OCA; a P310insC frameshift in exon 2 and an IVS2-7t-->a,-10
      11deltt splice junction mutation in exon 3. Here we report a prenatal diagnostic
      study of a subsequent fetus of the above family that was at 25% risk of OCA1.
      SSCP/heteroduplex screening, restriction enzyme digestion, and allele-specific
      oligonucleotide hybridization analyses of DNA obtained by chorionic villus
      sampling indicated that the fetus was a compound heterozygote for the paternal
      P310insC and the maternal IVS2-7t-->a,-10-11deltt mutations. The diagnosis was
      later confirmed by observation of poorly pigmented irides of the abortus
      terminated at the 18th week of gestation. This approach provides a fast and
      reliable method for DNA-based prenatal diagnosis when specific mutations are
      known in families at high risk of OCA1.

PMID- 9560950
TI  - DNA typing of HLA in the patients with moyamoya disease.
AB  - Moyamoya disease is a clinical entity demonstrating a chronic occlusion of the
      cerebrovascular system. Although some possible etiological factors have been
      postulated, the etiology of this disease is still unknown. So far, some
      investigations have suggested the association between moyamoya disease and HLA in
      the serological typing. However, DNA typing of HLA have not been performed yet.
      Thus, we performed DNA-typing of HLA in the unrelated Japanese patients with
      definite moyamoya disease, using the polymerase chain reaction-sequence specific
      oligonucleotide probe (PCR-SSOP) technique. In the total patients, DQB1*0502 had
      a positive association with the disease. On the other hand, DRB1*0405 and
      DQB1*0401 showed a negative association. In comparing the early-onset and late
      onset groups, two groups did not share the same disease associated alleles at
      all. Thus, the etiology of moyamoya disease seem to have a genetic background.
      Furthermore, different genetic factors might also be involved in the difference
      between the early-onset and late-onset groups.

PMID- 9560951
TI  - Dual-color fish analysis of breakpoints on Robertsonian translocations.
AB  - We investigated six Robertsonian translocations, including two cases of
      rob(13q14q); one of rob(14q21q), one of rob (13q22q), and two of rob(21q21q), by
      means of fluorescence in situ hybridization (FISH) using five repetitive DNA
      probes: two alpha-satellite DNAs (D21Z1/D13Z1 and D14Z1/D22Z1), satellite III
      DNA, beta-satellite DNA, and ribosomal DNA. Single color FISH successfully
      defined the breakpoints in four cases of the six. Since the remaining two cases,
      rob(13q22q) and rob(21q21q), revealed to retain rDNA, we tried to define the
      breakpoints in detail by dual color FISH in these rare types. In the rob(13q22q)
      the chromosomal breakage on chromosome 22 was likely to have occurred within the
      rDNA region and that the chromosome 13 breakpoint was within the alpha-satellite
      region. In one rob(21q21q) case we defined the breakpoint on one chromosome
      distal to, or within, the beta-satellite region distal to the rDNA, and the other
      chromosome breakage had occurred within alpha-satellite DNA. Our results
      underscored the power of dual-color FISH for defining the precise locations of
      breakpoints in Robertsonian translocations.

PMID- 9560952
TI  - Fish mapping of a translocation breakpoint at 6q21 (or q22) in a patient with
      heterotaxia.
AB  - Heterotaxia is a congenital lateralization defect of visceral organs. As several
      single-genes that act on the formation of left-right asymmetry during
      embryogenesis have been identified in animals, a defect in the similar system may
      play a role in heterotaxia in man. We previously reported a Japanese girl with
      heterotaxia associated with a de novo balanced translocation (6;18)(q21 or
      q22;q21.3 or q22). In the present study, based on a hypothesis that one of the
      putative situs-determining genes is disrupted at a breakpoint of the
      translocation, we first isolated a yeast artificial chromosome (YAC) clone
      covering a breakpoint, 6q21 (or q22) of the translocation. Then, using STSs
      mapped on the YAC, we isolated bacterial artificial chromosome (BAC) clones
      spanning the breakpoint. FISH analysis using the BAC clones as probes revealed
      that the breakpoint is confined to a segment between two STS loci, WI-4066 and
      the CHLC.GATA6B06.192, within a genetic distance of 1.4 cM. The human connexin43
      gene was not disrupted in our patient, although mutations of this gene have been
      reported in patients with complex heart disease and heterotaxia. The molecular
      localization of the translocation breakpoint in our patient may contribute to the
      positional cloning of a putative heterotaxia gene.

PMID- 9560953
TI  - Allelic frequencies of twelve dinucleotide repeat marker loci on chromosome 13 in
      the normal Japanese population.
AB  - To establish a genotypic database for dinucleotide repeat marker loci in the
      Japanese population, we determined allelic frequencies of 12 such markers on
      chromosome 13 and compared them with data from Caucasians in the GDB archive. The
      average heterozygosity (79%) for the 12 loci was the same for the two
      populations. However, allelic distributions at two of the marker loci were quite
      different. These data will be useful for disease studies in the Japanese
      population that involve linkage or sibship-pair analyses, or association studies.

PMID- 9560954
TI  - Agenesis of corpus callosum in three sibs.

PMID- 9560955
TI  - Characterization of marker chromosomes by fish using microdissected probes from
      old Carnoy-fixed cells: report of two cases.
AB  - We reported on two patients with a de novo marker chromosome of which the origins
      were successfully identified by FISH using microdissected probes. These probes
      were established by microdissections of extra chromosomal segments from Carnoy
      fixed cells stored at -20 degrees C for several years. Using these probes, we
      could verify partial 1q32 trisomy in a patient with 17p+ as well as partial 16q2
      trisomy in another patient with 4p+.

PMID- 9560956
TI  - Direct insertion of euchromatic material from chromosome Y in the X-chromosome in
      hypogonadotropic hypogonadisms with Crohn's disease.
AB  - The relationship between chromosomal abnormalities and Crohn's disease has not
      been established. Crohn's disease is associated with inflammation of the bowel,
      severe abdominal pain and chronic diarrhea. Its etiology is not known at present.
      A recessive gene with incomplete penetrance is thought to be a factor which does
      not follow simple mendelian inheritance. We report a case, where the euchromatin
      material of Y chromosome (p11.1 p11.2) has been directly inserted into the long
      arm of the X chromosome (q21.2), and is assumed to be the most likely cause of
      hypogonadotropic hypogonadism in this patients. It could also be that the
      function of the testis-determining factor (SRY) has been disrupted due to the
      insertion, causing loss of testicular development.

PMID- 9560957
TI  - Met 235 Thr polymorphism of angiotensinogen in Indonesians.

PMID- 9560958
TI  - [Cancer in children does not have to be painful. Efficient analgesia provided by
      skilled personnel is a the children's right].

PMID- 9560960
TI  - [Increased patient participation requires new fees].

PMID- 9560959
TI  - [Fetal monitoring does not prevent growth retardation. Preparedness for
      unexpected complications is the most significant benefit].

PMID- 9560961
TI  - [Why does the time go faster?].

PMID- 9560962
TI  - [Must I prescribe over-the-counter drugs?].

PMID- 9560963
TI  - [Omega-3 fatty acids against schizophrenia?!].

PMID- 9560964
TI  - [Are famciclovir and valaciclovir truly effective in the treatment of shingles?].

PMID- 9560965
TI  - [Disability evaluation: "Society takes advantage of physicians--and physicians
      let it go"].

PMID- 9560966
TI  - [Pain in children with cancer is mostly caused by treatment and interventions.
      Personnel would like to have more time for analgesic care and more training].

PMID- 9560967
TI  - [Vaccination against cancer soon a therapeutic possibility. B-cell tumors,
      colonic cancer and melanoma may be suitable for this treatment].
AB  - The theoretical basis of cancer vaccination having been well established during
      the past two decades, the translation of this knowledge into clinically
      applicable immunisation procedures is now an urgent need. Numerous antigenic
      preparations are available that are capable of inducing specific anti-tumour
      immunity which can be augmented by appropriate cytokines. Promising tumour
      vaccination results have been obtained in B-cell malignancies, colorectal
      carcinoma, and melanoma; tumour regression has been noted in myeloma, non-Hodgkin
      lymphoma, colorectal carcinoma, and melanoma patients, and significantly
      prolonged disease-freed survival in non-Hodgkin lymphoma and colorectal carcinoma
      patients. The presence of only minimal residual disease would seem to be a
      clinical prerequisite for tumour vaccination.

PMID- 9560968
TI  - [Fetal growth retardation is difficult to detect. Quality criteria for obstetric
      care are not functioning in the clinical practice].
AB  - In a study of the practical efficacy of quality criteria for obstetric care, it
      was found that fetal growth disorders are difficult to detect, even when growth
      retardation is suspected. Examination of the quality indicator, unrecognised SGA
      (small for gestational age), showed barely half the cases of subnormal
      gestational age-related birthweight.

PMID- 9560969
TI  - [Traumatic stress in adult refugees: when ill-health is silent or speaks broken
      Swedish].
AB  - It is well established that a significant proportion of refugees in Sweden have
      had traumatic experiences prior to immigration, causing mental and psychosomatic
      disorders. The actual frequency is difficult to assess because of methodological
      problems. Of refugees resettled in Stockholm county in 1996, 13 per cent were
      immediately referred to specialised trauma centres, thus comprising half of all
      referrals. Moreover, it has to be borne in mind that underdiagnosis is common in
      clinical practice. In the article, the relevance of accessible data, the clinical
      picture and epidemiological issues are discussed with regard to the refugee
      population.

PMID- 9560970
TI  - [Now who was Asklepios?].

PMID- 9560971
TI  - [Drunken driver examinations. CD-transferrin is a valuable marker of alcohol
      consumption].
AB  - The article reports findings in a study of 198 subjects attending a psychiatric
      out-patient clinic, with known or suspected high alcohol consumption during a 12
      month period, about half of whom had had their driving licences revoked. The
      level of carbohydrate-deficient transferrin (CDT) was found to be a valuable
      marker of alcohol consumption, and a useful adjunct to the measurement of liver
      enzymes. Both GGT (gamma-glutamyltransferase) and CDT levels were significantly
      higher in high alcohol consumers than in low consumers. Alcohol the two markers
      did not differ from each other in statistical significance, CDT was associated
      with greater sensitivity and specificity; the sensitivity of CDT was 69% for men
      and 79% for women, as compared with 62% and 40%, respectively, for GGT; the
      specificity of CDT was 81% for men and 100% for women, as compared with 82% and
      72%, respectively, for GGT. Together, GGT and CDT detected 91% of the male and
      93% of the female high consumers. Among younger men, CDT values were higher in
      the subgroup with a history of traffic offences than in the subgroup without such
      a history, thus suggesting that CDT levels may be increased by heavy weekend beer
      consumption. A few cases of false-positive CDT results were found to be
      attributable to genetic anomalies of the transferrin molecule. Cases
      characterised by disparity between the CDT level and the clinical picture require
      further, more specific, analysis. Used in combination with GGT, CDT is thus a
      feasible marker for use in monitoring alcohol consumption in drivers needing to
      qualify for the restoration of their licences.

PMID- 9560972
TI  - [Time to break up "psychosomatic families"! The model is not empirically
      supported].

PMID- 9560973
TI  - [To compare clinics, a considerate handling].

PMID- 9560974
TI  - [Topic problems of gerontology in otorhinolaryngology].
AB  - The paper characterizes age-specific involution of the ENT tissues, acoustic and
      vestibular analyzers, hearing and equilibrium defects. Original investigations of
      the authors give wider possibilities of early detection of age-related failure of
      the internal ear functions. Relevant tests are proposed.

PMID- 9560975
TI  - [Problem of cochlear implantation: brief introduction].
AB  - The only method of hearing rehabilitation for patients with severe hypoacusis and
      peripheral deafness is cochlear implantation consisting of insertion of
      electrodes into the scala tympani and direct electric impulse stimulation of the
      auditory nerve adjusted to the input acoustic signal. Only few such operations
      have been performed in this country. Much effort should be devoted to training of
      specialists and advocating this method among practitioners.

PMID- 9560976
TI  - [Acoustic evoked potentials in patients with vocal problems in relation to their
      hearing in wide frequency range].
AB  - The function of different compartments of the acoustic analyser was assessed by
      the findings at tonal audiometry in standard and extended range of frequencies
      (10, 12, 14 and 16 kHz) as well as by characteristics of acoustic evoked
      potentials. A total of 62 patients with chronic vocal dysfunction (CVD) and 20
      subjects with normal hearing and voice were examined. CVD patients were found to
      have: normal hearing both in standard and extended range of frequencies (25.8%);
      normal hearing in standard but defective one in extended range of frequencies
      (51.6%); defective hearing sensitivity to tones both in standard (4, 6 and 8 kHz)
      and extended frequency range (22.58%). CVD patients with abnormal hearing in the
      extended frequency range exhibited affection of the brain stem and cortical
      compartments of the acoustic analyser. Acoustic evoked potentials were especially
      abnormal in patients with high hearing thresholds (17.4 +/- 1.6; 25.8 +/- 1.9,
      29.7 +/- 2.1 dB) in standard frequency range (4, 6 and 8 kHz), respectively. In
      such patients the disease ran a protracted course with frequent relapses. These
      findings can help in making decision on the treatment policy, occupational
      fitness expertise and selection of patients with vocal professions.

PMID- 9560977
TI  - [Transplantation of fetal tissues in otorhinolaryngology: current status and
      prospects for the future].
AB  - Insufficient efficacy of treatment of neurosensory hypoacusis makes investigators
      search for new methods. Transplantation of fetal tissue taken from healthy
      embryos of gestation stage II tried in various fields of medicine, such as
      neurology, endocrinology, surgery, etc., was also tested in management of various
      forms of neurosensory hypoacusis. Endonasal, endaural, endolumbal and
      intracochlear methods of the transplantation are detailed. Results of combined
      dynamic audiological control of these patients including tonal threshold
      audiometry in extended frequency range are presented. A 1-year follow-up provided
      evidence in favour of endolumbal and intracochlear transplantation. Further
      investigations are needed.

PMID- 9560978
TI  - [Validation of therapeutical policy choice in exudative otitis media].
AB  - 132 patients with diagnosis acute or subacute exudative otitis media were treated
      conservatively (n = 79) or surgically (n = 53). Conservative treatment was
      effective in 41% of the cases, surgical treatment produced positive results in
      62.3%. The operative treatment combined elements of endoscopic nasal surgery and
      methods used in tympanoplasty, plastic treatment of the auditory tube, surgery of
      the internal ear.

PMID- 9560979
TI  - [Plastic reconstruction of mastoid cavity in patients with chronic suppurative
      otitis media].
AB  - The authors describe a mastoidoplasty modification--repair of the retrotympanal
      cavity with a large osteomusculoperiosteal graft on the lower feeding pedicle.
      This intervention was conducted in 25 patients with otitis media purulenta
      chronica with cholesteatoma and in 6 patients with incomplete epidermization of
      the cavity after radical operation on the ear. Prior to and following the
      operation turundas containing mixed salts of acid ethers of cellulose, bound
      calcium ions and antibiotics were inserted into the external acoustic meatus and
      postoperative cavity. The treatment duration was shorter. The effect was achieved
      in 27 patients.

PMID- 9560980
TI  - [Congenital malformations of nose and paranasal sinuses].
AB  - 410 patients with malformations of the external ear or nasal cavity were
      examined. Basing on this evidence, clinical and diagnostic aspects of agenesias,
      hypogenesias, hypergenesia, dysgenesia, persistence and dystopias of the nose and
      intranasal structures are analyzed. Both severe and "minor" anomalies are
      considered. Endoscopic diagnosis of the malformations is described.

PMID- 9560981
TI  - [Current problems of temporary expert evaluation of disability due to ENT
      diseases].
AB  - The paper is concerned with problems of expert evaluation of disability due to
      ENT diseases including temporary disability, differentiation of temporary and
      persistent disability, indications for expert examination. Recommendations for
      experts making the decisions on temporary ENT disability are given. Medical and
      social factors of ENT disability, especially occupational risks, are analysed.

PMID- 9560982
TI  - [Application of polymeric endoprostheses in surgery of external ear].
AB  - Biocompatible polymeric endoprostheses EFOS are offered for endoprosthetic
      reconstruction of the external acoustic meatus in atresia. Such endoprostheses
      are safe for the adjacent tissues. Moreover, such prostheses contain
      antibacterial drugs (quinoxidine, dioxidin) and substances promoting tissue
      regeneration (orotic acid derivatives). This provides good epithelization of the
      walls of the newly established external acoustic meatus and sufficient lumen of
      the organ. The removal of the endoprosthesis is recommended on the postoperative
      day 90-120 in the outpatient setting.

PMID- 9560983
TI  - Postoperative use of gelecel sorbent in patients with chronic suppurative otitis
      media.
AB  - Local sorption therapy of postoperative wounds in patients with exacerbation of
      otitis media purulenta chronica with gelecel stimulates cleansing of the wounds
      from pyonecrotic substances on postoperative day 2-3. Regeneration in the
      trepanation or radical cavity starts on day 2-3. Intoxication ceased 2 days
      earlier compared to the procedure with the use of medical gauze. To prevent
      dehydration of the soft tissue gelecel should be applied on postoperative day 5
      6.

PMID- 9560984
TI  - [Congenital parotid fistula].
AB  - 21 cases of congenital parotid fistula are reported. The patients' age ranged
      from 7 to 50 years. Dissection of the fistula under local anesthesia was made in
      9 patients. A 7-year-old patient was operated under intravenous calipsol
      anesthesia. Four kinds of the fistula depending on its shape and size are
      described. Two of them cause no trouble, the other two manifest from early
      childhood with inflammation, recurrences with abscesses. In such cases the
      fistula should be radically removed.

PMID- 9560985
TI  - [An unusual complication of chronic suppurative otitis media].

PMID- 9560986
TI  - [A rare case of cyst from the skull base simulating recurrence of peritonsillar
      abscess].

PMID- 9560987
TI  - [Esthesioneuroepithelioma combination with choanal polyp].

PMID- 9560988
TI  - [Polypous rhinosinusitis].

PMID- 9560989
TI  - [Removal of palatine tonsils].

PMID- 9560990
TI  - [The use of human skin reflectance spectra for the quantitative assessment of
      individual sensitivity to ultraviolet radiation].
AB  - Reflection spectra of human skin of various ethnic types in the range of 370-790
      nm were measured and analyzed. Correlation between reflection coefficients and
      minimal erythemal doses was estimated. The formula has been devised which is
      suitable for defining minimal erythemal doses both for open and closed parts of
      the body irrespective of pre-exposition to sun radiation.

PMID- 9560991
TI  - [An analysis of the clinical effects of ion-parametric magnetotherapy].

PMID- 9560992
TI  - [The laser therapy of hypertension patients in the initial stages].
AB  - The effect of low-energy laser irradiation used as monotherapy was studied in 42
      patients with early essential hypertension. Hypotensive and antioxidant effects
      of laser therapy, its ability to decrease total peripheral resistance were more
      pronounced in patients with stage I hypertension.

PMID- 9560993
TI  - [The seasonal nature of the course of ischemic heart disease and the prophylactic
      correction of the lipid structure of the erythrocyte membrane using laser
      radiation].

PMID- 9560994
TI  - [The magnetic-laser therapy of patients with complicated forms of varicose
      veins].

PMID- 9560995
TI  - [A comparative evaluation of the effect of an extremely high-frequency
      electromagnetic field on cerebral hemodynamics in hypertension patients exposed
      in different reflexogenic areas].
AB  - A single session and multiple sinocarotid and temporal exposures to EHF
      electromagnetic field in patients with stage I and II hypertension had different
      effects on cerebral circulation Variants of the above treatment are proposed.

PMID- 9560996
TI  - [A unit setup and experience in using pulsed barotherapeutic conditioning in a
      regimen of atmospheric pressure fluctuations every other day in correcting the
      meteoropathic reactions of patients with diseases of the circulatory organs].

PMID- 9560997
TI  - [The mathematical aspects of constructing a system for choosing the treatment
      method at a health resort in chronic nonspecific lung diseases].
AB  - The paper presents the analysis of present-day approaches to solution of the
      problem of spa-treatment method choice. Principal mathematical means and
      methodological approaches consist of; formalization of the subject field;
      accumulation of sufficient clinical material; classification of the patients'
      condition, functional changes and methods of treatment, multivariate (cluster,
      factor), inductive formation of concepts, models of thinking, etc.

PMID- 9560999
TI  - [The combined use of dry-air carbon dioxide baths and applications of peloids at
      low temperatures in the rehabilitation of patients with psoriatic arthritis].
AB  - Low-temperature peloids and dry effervescent baths were tried in the treatment of
      106 patients with psoriatic arthritis. The response was achieved in 70% of
      patients. The articular index, psoriatic lesions of the skin, inflammation
      diminished for 6-9 months.

PMID- 9560998
TI  - [An SHF electromagnetic field (460 MHz) combined with the preparation Tribimol in
      treating duodenal peptic ulcer associated with Helicobacter pylori].
AB  - Epigastric exposure to EHF (460 MHz) electromagnetic field and administration of
      Tribimol were combined in the treatment of 103 patients with uncomplicated
      duodenal ulcer. As shown by clinical, endoscopic and morphological examinations,
      biochemical and imprint tests for Helicobacter pylori, intragastric pH-metry, the
      method is pathogenetically sound and can be recommended for combined treatment
      and rehabilitation of patients with duodenal ulcer associated with Helicobacter
      pylori.

PMID- 9561000
TI  - [An experimental rationale for the use of sulfide sludge in adjuvant arthritis].
AB  - The experiments on 176 Wistar rats were performed for the first time to clarify
      mechanisms underlying anti-inflammatory action of the Deshembinskoe Lake mud in
      experimental arthritis. The new data obtained gave evidence supporting
      application of Deshembinskoe Lake mud in inflammatory diseases of the joints.

PMID- 9561001
TI  - [The use of millimeter waves in neurosurgery under electrophysiological control].
AB  - Patients with organic CNS lesions including epileptic syndrome can be treated
      using indirect influence of millimetric waves upon major brain regulatory systems
      via specific peripheral receptor fields under control of adequate bioelectric
      criteria. 42 brain-affected patients were studied. The above method used as a
      part of combined surgical treatment resulted in stable functional restoration and
      normalization of bioelectric brain activity.

PMID- 9561002
TI  - [Microzonal physiotherapy of the neck and face area].

PMID- 9561003
TI  - [The effect of a single inhalation of mineral water on the blood hormonal status
      in healthy volunteers].
AB  - Concentrations of ACTH, TTH, STH, LH, PSH, hydrocortisone, insulin, glucagone,
      triiodthyronine, thyroxine, aldosterone, glucose and unesterified fatty acids
      (NEFA) were measured in the blood of 23 healthy male volunteers aged 18 to 35
      years 15, 30 and 60 min after a single nose inhalation and oral intake of mineral
      water Essentuki No. 17. Inhalation of Essentuki No. 17 stimulated secretion of
      the hormones and some parameters of metabolic reactions: the levels of glucose,
      NEFA, hydrocortisone, aldosterone, TTH, PSH and LH rose while those of insulin
      and growth hormone decreased. Oral intake of this water brought about the same
      changes in the hormone status except blood insulin the levels of which went up.

PMID- 9561004
TI  - [Magneto- and cryotherapy of diseases of the locomotor system].

PMID- 9561005
TI  - [The therapeutic use of Chokrak mud].

PMID- 9561006
TI  - [The catalytic activity of medicinal mineral waters].

PMID- 9561007
TI  - [The basic climate categories of western Siberia from the viewpoint of health
      resort and recreational development].

PMID- 9561008
TI  - [Traction of the extremities in patients with osteoarthritis (a review of the
      literature)].

PMID- 9561009
TI  - Radiologic versus surgical placement of vena cava filters: a comparative study of
      cost, time and complications.
AB  - OBJECTIVE: To compare the cost- and time-effectiveness of 2 methods of placement
      of vena cava filters for the prevention of pulmonary embolism: the radiologic
      percutaneous placement of the Vena Tech LGM filter and the surgical cutdown
      placement of the 24 Fr Greenfield filter. METHODS: Retrospective review of
      radiologic and clinical records for 15 consecutive patients who had the Vena Tech
      LGM filter placed radiologically and 15 consecutive patients who had the
      Greenfield filter placed surgically. Factors studied were cost, procedure time,
      waiting time and rates of immediate and delayed complications. The follow-up
      period ranged from 1 to 26 months (mean 7 months). RESULTS: The procedure cost
      for the radiologic method was $702 less than for the surgical method. The
      procedure time for the radiologic method was 30 minutes shorter, and the waiting
      time for placement was also shorter. There was no difference in the complication
      rates following each procedure. The higher cost of the Greenfield filter
      accounted for 80% of the total cost difference. CONCLUSION: The radiologic
      percutaneous method of filter placement is preferred over the surgical cutdown
      method because of its benefits in terms of cost and time with no increase in
      risk. However, when the difference in cost between filters is taken into account,
      there is little difference in overall costs for the 2 methods. Therefore,
      radiology and surgery departments can place a filter percutaneously at a similar
      cost. Other factors such as waiting times, complication rates, venography
      capabilities and physician interest in performing the procedure will dictate
      which department places the filter.

PMID- 9561010
TI  - Complications of radiologically placed central venous ports and Hickman catheters
      in patients with AIDS.
AB  - OBJECTIVE: To determine any differences in the complications following radiologic
      placement of 2 devices--Hickman catheters and central venous ports--to permit
      long-term central venous access in patients with AIDS. PATIENTS AND METHODS:
      Thirty-eight patients with AIDS received 52 long-term central venous access
      catheters. Seventeen received 23 Hickman catheters and 27 received 29 central
      venous ports (hence, 6 patients received both). Complications rates were
      determined retrospectively from clinical records and radiologic studies. RESULTS:
      The only acute complications were pneumothoraces--3 in the patients receiving
      Hickman catheters and 2 in the patients receiving central venous ports.
      Infections developed in 12 of the patients receiving Hickman catheters a median
      of 53 and a mean of 96 days after placement. Infection developed in 8 of the
      patients receiving central venous ports a median of 125 days and a mean of 184
      days after placement. This difference was statistically significant (p < 0.001).
      The most common organism in these infections was Staphylococcus aureus. The only
      other nonacute complication was 1 nonocclusive thrombosis of the superior vena
      cava, which occurred in a patient with a Hickman catheter 240 days after
      placement and resolved once the catheter was removed. CONCLUSION: Central venous
      ports are preferred over Hickman catheters for long-term central venous access in
      patients with AIDS.

PMID- 9561011
TI  - Osseous tumours of the foot: a pictorial essay.

PMID- 9561012
TI  - Focal osteolysis as a complication of therapy for Paget's disease: case report.

PMID- 9561013
TI  - Bone dysplasias: an introduction.
AB  - Although individual bone dysplasias are rare, as a group they are relatively
      common and have a significant effect on morbidity and mortality at all ages. In
      this brief introduction, radiologic classification, diagnosis and differential
      diagnosis are given. The radiologic diagnosis is emphasized, since distinction
      among the various bone dysplasias is based largely on radiographic findings.
      Prenatal diagnosis relies heavily on high-resolution real-time ultrasonography of
      the fetus. Precise antenatal ultrasonographic diagnosis of a bone dysplasia may
      be very difficult; however, accurate differentiation of a lethal versus a
      nonlethal anomaly is relatively easy. There has been a recent explosion of
      knowledge about the genetic basis of skeletal dysplasias. Collagen gene mutations
      have been found to be responsible for osteogenesis imperfecta and many other bone
      dysplasias. The locations of the genes implicated in achondroplasia and some
      other chondrodysplasias are now known. Histologic analysis of the growth plate
      may also provide specific diagnostic features in achondroplasia and other bone
      dysplasias. A team approach is mandatory for the diagnosis and management of this
      fascinating and challenging group of diseases.

PMID- 9561014
TI  - Osteogenesis imperfecta: a review.
AB  - The wide spectra of the clinical features, classification, genetics and imaging
      features of osteogenesis imperfecta (OI) are discussed, especially in the context
      of distinguishing the condition from child abuse. A broad general knowledge of
      the clinical and genetic aspects of the disease, as well as the imaging features
      of OI, is required for radiologists to knowledgeably provide the proper diagnosis
      and to participate responsibly in a team approach with geneticists, clinicians,
      lawyers and child protection services. There are 4 major types of OI, ranging
      from mild to severe. The diagnosis is made from clinical, genetic and
      radiographic features. The complications of OI and the use of bone mineral
      density measurements, collagen analysis and prenatal ultrasonography are
      presented. Their clinical relevance to the diagnosis of OI are discussed. Skin
      biopsy for collagen analysis may be needed to aid in the diagnosis in confusing
      or mild cases. It is important to distinguish OI from child abuse in order to
      protect an abused child or to avoid an improper accusation of child abuse in a
      child with obvious OI.

PMID- 9561015
TI  - Malignant suprasellar gliomas: 4 case reports.

PMID- 9561016
TI  - Residents' corner. Answer to case of the month #53. Beta-thalassemia intermedia
      with extramedullary hematopoiesis.

PMID- 9561017
TI  - Residents' corner. Answer to case of the month #54. Cecal lipoma with colocolic
      intussusception.

PMID- 9561018
TI  - [Circadian rhythm of melatonin in liver cirrhosis].
AB  - The liver plays an important role in the intermediate metabolism of numerous
      substances involved in hormonal action. Starting from the presupposition that the
      pineal has an inhibitory effect on the reproduction system through melatonin
      (aMT) and that hepatic cirrhosis can be included among the pathologies
      characterised by sexual disorders, the authors felt that it was interesting to
      evaluate the light/darkness rhythm of aMT in some patients suffering from hepatic
      cirrhosis in order to highlight the possible pathogenetic role of aMT in causing
      the altered sexual activity observed in this pathology. A total of 4 subjects (3
      males and 1 female), with a mean age of 60.5 years, suffering from hepatic
      cirrhosis and a matched group of healthy controls were included in the study.
      Circadian changes in aMT plasma levels and plasma levels before and after TRH
      stimulus (200 micrograms) of aMT and PRL were studied in all subjects. The
      results revealed the presence of a circadian rhythm of aMT with a nocturnal peak
      secretion in both groups; in patients with cirrhosis, however, the rhythm
      appeared to be "out of phase" and presented a late and prolonged increase in aMT
      compared to controls. Responses to TRH did not show any differences in aMT
      between the two groups, but the response to PRL was higher and longer than in
      hepatopathic patients. These findings showed an alteration in the secretory
      pattern of aMT in cirrhotic patients which can be attributed to reduced hormone
      metabolism at an hepatic level. The altered response to PRL is attributable to an
      altered neurotransmitter function at the central level.

PMID- 9561019
TI  - Prognostic significance of the estrogen-regulated proteins, cathepsin-D and pS2,
      in breast cancer.
AB  - The evaluation of prognostic factors for breast cancers is important for
      therapeutic decisions both at the time of surgery and during postoperative
      surveillance. Cathepsin-D (cath-D) is an estrogen inducible aspartyl protease.
      Studies have demonstrated two biological activities, at an acidic PH, of the
      protein: a mitogenic and a proteolytic activity; both the growth promoting
      activity and the extracellular proteolytic activity suggest that cathepsin D
      (cath-D) may have prognostic significance in breast cancer. Measurement of cath-D
      in breast tissue, in fact, is highly significant in predicting recurrence as well
      as disease free interval and overall survival. The pS2 is a small cysteine-rich
      protein specifically expressed under estrogen transcriptional control. Expression
      of the pS2 protein in breast carcinoma is a useful guide to prognosis and
      response to tamoxifen: appropriate adjuvant therapy can be selected on the pS2
      status of the tumor; patients with pS2 expression had better overall survival and
      a longer survival time after the first recurrence than those without pS2
      expression. For these reasons, these two new prognostic markers could be
      suggested as habit factors in breast cancer.

PMID- 9561020
TI  - [Differential diagnosis of fever of unknown origin. A case of adult onset Still
      disease].
AB  - BACKGROUND: A case of Still's disease in the adult, an uncommon seronegative
      rheumatoid arthritis-like disease with prominent systemic features is reported.
      This case did not show the typical clinical features and appeared like a fever of
      unknown origin. CASE REPORT: A 60 year-old female was admitted to the hospital
      for high fever occurred two months before without other important clinical
      symptoms and signs. Laboratory tests and morphologic images were negative for
      infectious diseases, tumours and immunological disorders. The course of the
      disease worsened and an hepatic failure threatened the patient life. The onset of
      many other typical clinical features, i.e. joints pain, characteristic skin rash,
      splenomegaly, throat pain, serositis and weight loss, led us to make a sure
      diagnosis and to save the patient with steroid therapy.

PMID- 9561021
TI  - [Correlation between pulmonary pharmacokinetics and pharmacodynamics support the
      hypothesis of the usefulness of ceftazidime at a single 1g daily dose in the
      treatment of bacterial exacerbation of chronic obstructive bronchopneumonia with
      moderate functional damage].
AB  - INTRODUCTION AND BACKGROUND: Experimental studies have shown that cephalosporins
      have an antibacterial effect in vivo even when their levels are above MIC for
      only 40-50% of dosing intervals, whereas maximum killing is obtained when
      concentrations are above MIC for 60-70% of the time. Since most patients treated
      with antibiotics have neutrophils and other natural defence mechanisms, it is
      likely that a bacteriostatic effect should be sufficient to induce an effective
      therapeutic response. METHODS: Given that in the potential sites of lung
      infection ceftazidime reaches significantly higher levels than the MIC of the
      most commonplace respiratory pathogens, even 8-12 hours after the administration
      of 1 g i.m., the authors evaluated the efficacy of treatment of renewed acute
      episodes of COPD using this antibiotic at a dose of 1 g once a day. In order to
      do this, 20 outpatients were enrolled in the study, half of whom presented
      moderate bronchial obstruction (FEV1 = 50-70% of theoretical) whereas the
      remainder presented marked bronchial obstruction (FEV1 = < 50% of theoretical).
      RESULTS: The 10 patients with moderate obstruction at the time of enrollment, who
      presented Haemophilus influenzae, Streptococcus pneumoniae or Moraxella
      catarrhalis as causal agents in the sputum (Escherichia coli was only isolated in
      one patient), showed a marked improvement following treatment with 1 g
      ceftazidime one a day. A real or presumed eradication of the causal microorganism
      was observed in all subjects. Treatment with ceftazidime at the dose of 1 g/die
      once a day was much less effective in patients with marked bronchial obstruction.
      Treatment was successful in 7 out of 10 subjects, but 2 of them relapsed within 2
      weeks. In this second group, Pseudomonas aeruginosa was found in the sputum of 3
      patients; one of the patients showed a persistence of the bacterium after
      ceftazidime treatment, and another presented reinfection 12 days after the end of
      treatment. The two patients in whom Staphylococcus aureus was isolated did not
      benefit from ceftazidime treatment at this dosage. One subject who initially
      presented Streptococcus pneumoniae in his sputum and was then thought to have
      recovered, underwent a new acute episode caused by Moraxella catarrhalis 2 weeks
      after the suspension of ceftazidime treatment. CONCLUSIONS: The therapeutic
      responses observed during this study suggest the possibility of using ceftazidime
      in a single daily dose of 1 g i.m. to treat those patients with exacerbations of
      COPD who only present moderately impaired functional symptoms. On the contrary,
      this type of therapeutic approach must be used with extreme caution in subjects
      with marked functional damage, although a satisfactory clinical response may be
      obtained in some cases. However, the small number of patients included in this
      study does not allow firm conclusions to be drawn. Only a study involving a
      larger group of patients could provide the necessary information to confirm the
      hypothesis for treatment put forward by the authors.

PMID- 9561023
TI  - [The new financing system in the Italian National Health Service. Implications
      for internal medicine].
AB  - Since 1995, the Italian National Health Service has begun to fund its hospitals
      on a DRG basis. This paper presents the main features of the DRG system as well
      as its likely implications for general internal medicine. The first part
      describes the introduction of DRGs in the US. The first paragraphs summarize the
      features of the US health-care system and particularly its private nature with
      two major exceptions: Medicare and Medicaid. The development of the DRG system
      and its adoption by Medicare are then described. Finally, the main effects of
      Medicare's DRG system are underlined: shorter hospital stays, fewer hospital
      admissions, several diagnostic and surgical procedures shifted from the inpatient
      to the outpatient setting, and apparently no negative quality implications. The
      second part focuses on Italy, in general and with specific reference to general
      internal medicine. For general internal medicine, the new funding system has two
      major implications. First, it may lead to the creation of larger medical
      departments including both the current general internal medicine divisions and
      the various specialties. Second, even under the current organisational structure,
      divisions will be increasingly required to produce positive financial margins. In
      this respect, general internal medicine divisions seem to be in a favourable
      position, especially in terms of costs (both per-diem and per-admission).

PMID- 9561022
TI  - [Laboratory diagnosis of intestinal micro-parasitosis in AIDS patients: state of
      the art].
AB  - BACKGROUND: The diarrhea, often associated with growing thin and weight loss, is
      important for nutritional state and quality of life in AIDS patients. It was
      demonstrated that patients with AIDS who present diarrhea have a greater degree
      of immunosuppression than those without diarrhea, predisposing the
      gastrointestinal tract to the action of protozoa, bacterial, viral, fungal
      pathogens which may cause morbidity and death. HIV-patients are particularly
      susceptible to protozoa infections. Cryptosporidium infection is among the most
      common causes of enteric disease but Microsporidium (Enterocytozon bieneusi) and
      Cyclospora are emerging as potentially important enteric pathogens in AIDS
      patients. In spite of frequent interest of gastrointestinal tract the knowledge
      of diarrhea syndromes AIDS-related are often greatly limited by diagnostic
      difficulties. OBJECTIVE: A review is made of the different laboratory methods
      employed in intestinal microparasitosis in the light of considerable
      dangerousness and aggressiveness of some protozoa on HIV-patients. METHODS: The
      methods for the diagnosis of intestinal microparasitosis are based particularly
      on direct diagnosis (macroscopic or microscopic examination at fresh or after
      concentration) or an immunological diagnosis. RESULTS: The laboratory methods
      available at present permit to evidence different protozoa not evidenced in the
      past and without invasive techniques. CONCLUSIONS: The etiological diagnosis of
      diarrhea in AIDS-patients is often difficult and/or disappointing.
      Epidemiological knowledge on protozoa pathology has been limited by diagnostic
      difficulties but their identification is important particularly because an
      increasing therapeutic regimens are now available to treat these infections.

PMID- 9561024
TI  - Differential responsiveness of murine T lymphomas to local growth and invasion
      factors may determine metastasis formation in the ovaries.
AB  - The murine T cell hybridomas BW-14 and BW-19, both derived from a fusion between
      the nonmetastatic BW 5147 lymphoma and a cytotoxic T cell line, differ in their
      capacity to metastasize to the ovaries. While ovary colonization by BW-19 cells
      is marginal and limited to the ovary follicles, BW-14 cells extensively colonize
      the complete ovary. The present study shows that the two T cell hybridomas
      respond differentially to ovary-derived migration and growth-modulating factors,
      in a way that correlates with their differential capacity to metastasize to the
      ovaries. More specifically, we observed that conditioned medium from cultured
      ovary fragments or from the ovary-derived granulosa cell line GRMO1V inhibited
      the migration of BW-19 cells in vitro, but stimulated the migration of BW-14
      cells. Likewise, the local hormone prostaglandin E2 (PGE2) and the steroid
      hormone progesterone, both known to be secreted by GRMO1V cells, stimulated the
      migration of BW-14 cells, indicating that the stimulatory effect of the
      conditioned medium can be at least partially ascribed to the action of these two
      hormones. In contrast, the migration of BW-19 cells was inhibited by PGE2. In
      addition to the modulatory effect on hybridoma cell migration, conditioned medium
      from the granulosa cell line GRMO1V inhibited the proliferation of BW-19 cells in
      vitro, an effect that is likely to be mediated at least partially by PGE2. The
      proliferation of BW-14 cells, on the other hand was, depending on the dilution
      used, stimulated or inhibited by GRMO1V-conditioned medium. Our findings indicate
      that the differential capacity of the T cell hybridomas BW-14 and BW-19 to
      metastasize to the ovaries is mediated by the differential action of granulosa
      cell-derived factors, in particular the sex hormone progesterone and the local
      hormone PGE2, on both the migration and proliferation of the T cell hybridomas.

PMID- 9561025
TI  - IL-10 inhibition of human prostate PC-3 ML cell metastases in SCID mice: IL-10
      stimulation of TIMP-1 and inhibition of MMP-2/MMP-9 expression.
AB  - The molecular mechanism by which IL-10 inhibits metastases was examined using a
      SCID mouse model. Human PC-3 ML subclones normally metastasize to the lumbar
      vertebrae (approximately 70% mice injected, n = 14/20) following intravenous
      injection in severe combined immunodeficient (SCID) mice. IL-10 treatment of the
      PC-3 ML cells (15 ng/ml for 36 h) and the SCID mice (0.03 mg/kg/day for 30 days)
      reduced the number of metastases to 5% of the mice (n = 1/20). More importantly,
      following discontinuation of IL-10 treatment on day 30, the mice remained tumor
      free and mouse survival rates increased dramatically (from < 30% in untreated
      mice) to about 85% in IL-10-treated mice. IL-10 did not appear to alter the
      growth rates or colony-forming ability of the PC-3 ML cells in vitro. Likewise,
      the growth of subcutaneous tumors and established bone marrow metastases was not
      inhibited by IL-10 treatment of the SCID mice. However IL-10 may inhibit the
      production of matrix metalloproteases (MMP) and prevent the establishment of
      metastasis. We therefore examined the influence of IL-10 on PC-3 ML production of
      MMP-2/MMP-9 and the tissue inhibitors of metalloproteinases (TIMP-1/2). Enzyme
      linked immunosandwich assays (ELISAs) revealed that IL-10 (15 ng/ml for 36 h)
      treatment of the PC-3 ML cells down-regulated MMP-2 and MMP-9 while up-regulating
      TIMP-1 (not TIMP-2) expression. Likewise, IL-10-treated mice exhibited similar
      changes in TIMP-1 and MMP-2/MMP-9 expression. The IL-10 effects were blocked by
      IL-10 receptor antibodies. In comparison to IL-10, IL-4 failed to influence
      metastasis or the expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 by PC-3 ML cells.
      We suggest that IL-10-regulated increases in the molar ratio of TIMP-1/MMP-9 and
      TIMP-2/MMP-2 might inhibit processes critical to the establishment of bone marrow
      metastasis.

PMID- 9561026
TI  - Immunophenotype of human HT29 colon cancer cell metastases in the lungs of scid
      mice: spontaneous versus artificial metastases.
AB  - The aim of this study was to compare the immunophenotype of the human colon
      cancer cell line HT29 tumour deposits in the lung which occurred spontaneously
      after subcutaneous implantation with those which arose after intravenous
      injection into severe combined immunodeficient (scid) mice. Irrespective of the
      route of implantation the colon cancer cells were readily observed in the lungs
      of the scid mice. Similar patterns of immunoreactivity for the proliferative
      markers (MiB-1, PCNA), and for the tumour suppressor gene (p53) were detected in
      both groups, and for carcinoembryonic antigen, with only minor quantitative
      differences in levels of marker expression. Whereas the marker CD44 variant 6
      gave very little reaction after either route, cytokeratin expression varied
      amongst the different cytokeratins (CK 7, 18 or 20), and with the route of
      implantation. CA125 and E-cadherin were weakly expressed after intravenous
      injection, but generally not after subcutaneous implantation. Vimentin was not
      demonstrated in any of the specimens examined. In general, the expression of
      proliferative markers, and of oncogenes, appears to be independent of the
      implantation route, whilst expression of cell adhesion molecules can be dependent
      on the route of implantation.

PMID- 9561027
TI  - Alpha-melanocyte-stimulating hormone blocks invasion of reconstituted basement
      membrane (Matrigel) by murine B16 melanoma cells.
AB  - We have examined the effect of alpha-melanocyte-stimulating hormone (alpha-MSH)
      on invasive ability of murine melanoma cell lines with different metastatic
      potential in a Matrigel invasion assay. alpha-MSH potently blocked the invasion
      of B16-BL6 cells with highly metastatic potential in a concentration-dependent
      manner, whereas it was less effective in inhibiting the invasion of weakly
      metastatic B16-F1 cells. Pretreatment of B16-BL6 cells with alpha-MSH resulted in
      a decrease of the adhesiveness to fibronectin and laminin substrates in a time
      dependent fashion. As assessed by zymographic analysis, alpha-MSH partially
      inhibited the production of matrix metalloproteinase (MMP)-2 and -9 from both
      cell lines to a similar degree without affecting the degradative activity of
      these MMPs. alpha-MSH was more potent in inhibiting the migration of B16-BL6
      cells towards both fibronectin- and laminin-coated substrates than that of B16-F1
      cells. The growth and morphology of B16-BL6 cells were not changed after a 7-day
      incubation with alpha-MSH. The number of lung tumor colonies markedly decreased
      when B16-BL6 cells were coinjected intravenously with 10(-6) M alpha-MSH.
      However, alpha-MSH had no effect on the experimental lung metastases by B16-F1
      cells. These results suggest that alpha-MSH suppressed the invasive and
      metastatic properties of B16 melanoma cells, and the degree of inhibition was
      associated with metastatic potential of B16 melanoma cells.

PMID- 9561028
TI  - Relationship of epidermal growth factor binding capacity to histopathologic
      features and prognosis in human renal cell carcinoma.
AB  - We studied the association between epidermal growth factor (EGF) binding capacity
      and histopathologic features or prognosis in human renal cell carcinoma (RCC) by
      Scatchard analysis in 67 patients. EGF binding capacity was significantly greater
      in metastatic than in nonmetastatic tumors, and in nuclear grade 3 than nuclear
      grade 1 tumors. Multivariate analysis revealed that tumor stage, nuclear grade,
      EGF binding capacity, and tumor size significantly correlated with overall
      survival. These results suggest that EGF binding may be an important determinant
      of prognosis in patients with RCC.

PMID- 9561030
TI  - Macromolecular contrast media-enhanced MRI estimates of microvascular
      permeability correlate with histopathologic tumor grade.

PMID- 9561029
TI  - Adhesion of human breast carcinoma to extracellular matrix proteins is modulated
      by galectin-3.
AB  - In this report, we have analyzed the adhesive interactions of a breast carcinoma
      cell line, BT-549, and its galectin-3-transfected subclone 11-9-1-4 with laminin,
      collagen IV and fibronectin. We determined that 11-9-1-4 cells adhered much more
      rapidly (within 1 h of plating) to laminin- and collagen IV-coated wells than the
      galectin-3 null expressing BT-549 cells. However, after 24 h, both cell lines
      fully adhered to laminin and collagen IV. Both cell lines also achieved maximum
      adhesion to fibronectin within 30 min. Not only did 11-9-1-4 express galectin-3
      in the usual punctate pattern on its cell surface, it demonstrated a higher
      surface expression of alpha 6 beta 1 integrin compared to BT-549. The 11-9-1-4
      cells were able to invade through matrigel-coated polycarbonate filters at
      approximately 3 times the rate of BT-549 parental cells. Our data suggest that
      galectin-3 is essential for adhesion to laminin and collagen IV but not
      fibronectin by breast carcinoma cells. In addition, galectin-3 expression may
      modulate the surface expression of some of the integrins specific for laminin and
      collagen IV adhesion and invasion of basement membrane by breast carcinoma cells.

PMID- 9561031
TI  - New liposomal liver-specific contrast agent for CT: first human phase I clinical
      trial assessing efficacy and safety.

PMID- 9561032
TI  - Contrast enhancement of the liver in healthy male volunteers following
      intravenous administration of FP 736-04.

PMID- 9561033
TI  - Efficacy of the hepatocyte-specific contrast medium FP 736-04 for CT in two
      models of experimental diffuse liver disease.

PMID- 9561034
TI  - Lipid-based blood-pool CT imaging of the liver.
AB  - RATIONALE AND OBJECTIVES: We have recently developed an iodinated lipid-based
      contrast agent capable of residing in the blood pool for extended periods of time
      relative to conventional water-soluble contrast agents. The purpose of this study
      was to examine the effects of combining this new blood-pool agent (ITG-PEG) with
      a hepatocyte-selective agent (ITG-LE; Molecular Biosystems) for accurate CT
      detection of small (< 10 mm) VX2 tumors in rabbit liver. MATERIALS AND METHODS:
      Preliminary pharmacokinetic analyses were conducted in SD rats (12) by injection
      of either I-125-labeled ITG-PEG or I-125-labeled ITG-LE followed by subsequent
      blood collection and quantification of radioactivity. Preliminary CT studies were
      conducted in both normal (3) and tumor-bearing NZW rabbits (2). Tumor-bearing
      rabbits were laparotomized and VX2 cells injected directly into the hepatic
      parenchyma to produce a total of eight focal lesions (2-10 mm diameter). Animals
      underwent CT scanning 10 days later with multiple techniques including
      noncontrast and helical i.v. enhanced (600 mg I/kg iohexol), and then 24 hours
      later using both ITG-PEG and ITG-LE (200 mg I/kg). Tissue density measurements
      (HU) of liver, tumor, and blood (descending aorta) were acquired in each case for
      comparison. Tumor morphology was verified by gross pathologic inspection.
      RESULTS: Pharmacokinetic analysis in rats as well as CT studies in normal rabbits
      revealed that ITG-PEG remains in the blood-pool phase for more than 2 hours
      following i.v. administration. In fact, blood density in normal rabbit obtained
      with ITG-PEG was 95.1 HU +/- 5.8 at 120 minutes compared to 90.7 HU +/- 6.1
      immediately after injection. Although liver enhancement was greater with iohexol
      (67 HU within 1 minute of injection), than for ITG-PEG/ITG-LE (32 HU, 60 minutes
      postinjection), liver to lesion ratios favored ITG-PEG/ITG-LE due to significant
      enhancement of tumor itself with iohexol (+40 HU). Tumor enhancement was minimal
      with ITG-PEG/ITG-LE. Lesions were subjectively much better defined with ITG
      PEG/ITG-LE with sharper edge definition. CONCLUSION: In these animal models, a
      new iodinated lipid-based contrast agent composed of both blood pool and
      hepatocyte-selective components afforded favorable CT imaging results compared to
      a conventional urographic agent, albeit at one-third the total iodine dose.

PMID- 9561035
TI  - Safety and pharmacokinetics of BR21, a liver-specific CT agent, in healthy
      volunteers.

PMID- 9561036
TI  - Evaluation of N,N'-bis-dimethyldiatrizoic acid analogs as liver imaging agents.

PMID- 9561037
TI  - Assessment of acute and reperfused myocardial ischemia using GdDTPA, GdDTPA
      cascade-24-polymer and albumin-GdDTPA.

PMID- 9561038
TI  - Investigation of MR contrast media utility with the VX-2 tumor model.

PMID- 9561039
TI  - Validation of intracoronary delivery of metalloporphyrin as an in vivo
      "histochemical staining" for myocardial infarction with MR imaging.

PMID- 9561040
TI  - Toward necrotic cell fraction measurement by contrast-enhanced MRI of reperfused
      ischemically injured myocardium.

PMID- 9561042
TI  - Selection of contrast medium for CT: what percentage of patients receiving CT
      needs nonionic contrast media (low-osmolarity contrast media)?

PMID- 9561041
TI  - Human pharmacokinetics and modeling of the concentration-attenuation relationship
      of a new liposomal liver-specific contrast agent for CT.

PMID- 9561043
TI  - Safety of carbon dioxide as a contrast medium in cerebral angiography.

PMID- 9561044
TI  - Clinical usefulness of iomeprol 400 mgl/ml in cardioangiography evaluation of
      patient discomfort and hemodynamic and ECG effects.

PMID- 9561045
TI  - Prospective randomized crossover pilot study of the safety and efficacy of carbon
      dioxide versus iodinated contrast for peripheral angiography.

PMID- 9561046
TI  - High-resolution harmonic gray-scale imaging of normal and abnormal vessels and
      tissues in animals.

PMID- 9561047
TI  - Phase II, placebo-controlled trial of MRX115 (Aerosomes) for left heart and
      myocardial perfusion imaging.

PMID- 9561048
TI  - Clinical experience with AF0150 (Imagent US), a new ultrasound contrast agent.

PMID- 9561049
TI  - Contrast-enhanced MRI of focal liver lesions: differentiation and detection of
      primary and secondary liver lesions using Resovist-enhanced versus gadolinium
      enhanced MRI in the same patient.

PMID- 9561050
TI  - Experimental hepatic dysfunction: evaluation by MR imaging with Gd-EOB-DTPA.

PMID- 9561051
TI  - Efficacy and safety of liver-specific MRI contrast agents in rats with hepatitis
      and cirrhosis.

PMID- 9561052
TI  - Multihance clinical pharmacology: biodistribution and MR enhancement of the
      liver.

PMID- 9561053
TI  - Dysprosium EOB DTPA: a new liver-specific contrast agent for computed tomography.

PMID- 9561054
TI  - Can contrast media Act as "pseudoantigens"?

PMID- 9561055
TI  - Effect of steroid pretreatment on contrast media-induced potassium release.

PMID- 9561056
TI  - Involvement of the lung in the histamine-releasing effects of iodinated contrast
      media.

PMID- 9561057
TI  - Contrast-enhanced magnetic resonance angiography in the coronary and peripheral
      arteries.

PMID- 9561058
TI  - Application of superparamagnetic iron oxide (AMI-227) for 3D phase-contrast MR
      angiography.

PMID- 9561059
TI  - Good resolution of contrast-enhanced MRA using USPIO on coronal plane
      acquisition: experimental evaluation of time-of-flight effect using flow phantom
      and animal study.

PMID- 9561060
TI  - Receptor-mediated mechanisms in contrast medium-induced renal vasoconstriction.

PMID- 9561061
TI  - Influence of iotrolan on renal cortical and outer medullary blood flow in the
      rat.

PMID- 9561063
TI  - Optimizing imaging techniques to reduce errors in microvascular quantitation with
      macromolecular MR contrast agents.

PMID- 9561062
TI  - Visualizing renal anatomy and function with 1-10,000-nm radiocontrast agents.

PMID- 9561064
TI  - T1 and T2 relaxometry of monocrystalline iron oxide nanoparticles (MION-46L):
      theory and experiment.

PMID- 9561065
TI  - Simultaneous use of Gd-DTPA and spin-lock imaging: a Phantom Study.

PMID- 9561066
TI  - Multisite study of the safety and efficacy of LumenHance, a new gastrointestinal
      contrast agent for MRI of the abdomen and pelvis.

PMID- 9561067
TI  - Pharmacokinetic and hemodynamic safety of two superparamagnetic agents, Endorem
      and Sinerem, in cirrhotic rats.

PMID- 9561068
TI  - Multicenter evaluation of the safety, tolerance, and efficacy of OptiMARK in
      magnetic resonance imaging of the brain and spine.

PMID- 9561069
TI  - Delayed adverse reaction of monomeric contrast media: comparison of plain CT and
      enhanced CT.

PMID- 9561070
TI  - Drug eruption caused by nonionic iodinated X-ray contrast media.

PMID- 9561071
TI  - Delayed hypersensitivity to X-ray CM: possible mechanisms and models.

PMID- 9561072
TI  - MR imaging of lymph nodes in patients with primary abdominal and pelvic
      malignancies using ultrasmall superparamagnetic iron oxide (Combidex).

PMID- 9561073
TI  - MR lymphography: evidence of extravasation of superparamagnetic nanoparticles
      into the lymph.

PMID- 9561074
TI  - Enhanced detection of thrombi with a novel fibrin-targeted magnetic resonance
      imaging agent.

PMID- 9561075
TI  - X-ray phototherapy for solid tumors.

PMID- 9561076
TI  - Contrast-enhancement properties of irradiated normal lymph nodes: initial
      experience with interstitially delivered iodinated nanoparticles.

PMID- 9561077
TI  - Diagnostic improvement of renal ultrasonography in humans after i.v. injection of
      perflenapent emulsion.

PMID- 9561078
TI  - Liver-tumor detection with ultrasound contrast: a blinded prospective study in
      rabbits.

PMID- 9561079
TI  - Safety of levovist injection in patients undergoing exercise stress
      echocardiography: a placebo-controlled study.

PMID- 9561080
TI  - Enhancement of power Doppler signals from breast lesions with the ultrasound
      contrast agent EchoGen emulsion: subjective and quantitative assessment.

PMID- 9561081
TI  - Blood-pool contrast agents for MRI: a critical evaluation.

PMID- 9561082
TI  - Kinetics of a novel blood pool agent (MP-2269) with persistent high relaxivity
      for MR angiography.

PMID- 9561083
TI  - Development of a novel nonaromatic small-molecule MR contrast agent for the blood
      pool.

PMID- 9561084
TI  - Evaluation of Gd-DOTA-labeled dextran polymer as an intravascular MR contrast
      agent for myocardial perfusion.

PMID- 9561085
TI  - Contrast-enhanced MR angiography and first-pass renal perfusion imaging using MS
      325, an intravascular contrast agent.

PMID- 9561086
TI  - Use of intravascular contrast agents in MRI.

PMID- 9561087
TI  - Factors determining tumor contrast enhancement-time curves.

PMID- 9561088
TI  - Dynamic susceptibility contrast MR imaging for the evaluation of probable
      Alzheimer disease: a cost-effectiveness analysis.

PMID- 9561089
TI  - Stimulated acoustic emission imaging ("sono-scintigraphy") with the ultrasound
      contrast agent Levovist: a reproducible Doppler ultrasound effect with potential
      clinical utility.

PMID- 9561090
TI  - Evaluation of new thrombus-specific ultrasound contrast agent.

PMID- 9561091
TI  - Targeting of ultrasound contrast material: selective imaging of microbubbles in
      vitro.

PMID- 9561092
TI  - MRX 501: a novel ultrasound contrast agent with therapeutic properties.

PMID- 9561093
TI  - Use of intravenous Optison contrast echocardiography reduces downstream resource
      use and enhances cost savings.

PMID- 9561094
TI  - Some recent advances in leukotriene research.

PMID- 9561095
TI  - Practical aspects of prostaglandin E1 before and after solid organ
      transplantation.

PMID- 9561096
TI  - Prostaglandins in liver transplantation.
AB  - This review summarizes experimental studies and clinical experiences with
      prostaglandins in liver transplantation emphasizing two randomized, double
      blinded placebo controlled clinical trials of prostaglandin E1 (PGE1) involving
      nearly 300 liver transplant recipients. Resource utilization and pharmacoeconomic
      aspects are also discussed. In the randomized trials, PGE1 did not affect patient
      and graft survival. Acute cellular rejection and primary allograft non-function
      were not reduced by PGE1. Postoperative renal failure was significantly less
      frequent among PGE1 patients in both trials and in one study perioperative blood
      product utilization was significantly lower. PGE1 treated patients had reduced
      intensive care unit length of stay, shorter hospitalization, and significantly
      lower total health care charges. Despite its failure to show improvements in
      patient and graft survival, rejection, or primary non-function, PGE1 use in
      hepatic allograft recipients reduces morbidity and results in notable reduction
      in the cost of liver transplantation.

PMID- 9561097
TI  - Prostaglandins in heart transplantation.

PMID- 9561098
TI  - Eicosanoids in periodontal diseases: potential for systemic involvement.
AB  - The potential application of gingival crevicular fluid (GCF) levels of
      prostaglandin E2 (PGE2) for predicting periodontal disease severity and
      reflecting disease activity has been described by several investigators. The
      potential application of GCF levels of PGE2 for predicting amniotic fluid levels
      of PGE2, and thereby estimating risk of preterm low birth weight, has not been
      explored until recently. The fact that intraamniotic levels of many inflammatory
      mediators, such as prostaglandin E2, increase during pregnancy and peak at
      delivery suggests that these mechanisms play an important role in normal
      physiologic parturition. There is increasing evidence to suggest that the
      presence of a subclinical endogenous Gram-negative infection of periodontal
      disease may present a systemic challenge sufficient to initiate the onset of
      premature labor, either as a source of lipopolysaccharide (LPS, endotoxin) and/or
      through stimulation of secondary inflammatory mediators such as PGE2 and
      interleukin 1 beta (IL-1 beta). This pilot investigation determines associations
      among the levels of PGE2 in gingival crevicular fluid, within serum, and within
      amniotic fluid of 18 women who were undergoing routine amniocentesis during early
      midtrimester, in an attempt to reveal new baseline data regarding the
      relationship between periodontal inflammatory mediators and intraamniotic
      mediators during normal parturition. Full-mouth periodontal examinations were
      performed and samples of GCF, serum and amniotic fluid were collected from each
      subject for the quantitative assessment of PGE2 by radioimmunoassay (RIA).
      Results of a pairwise regression analysis model reveal that PGE2 levels within
      the GCF are positively associated with intraamniotic PGE2 levels at the P = 0.018
      level of significance. Thus, gingival crevicular levels of PGE2 may be used to
      provide an indirect estimate of the amniotic fluid levels of PGE2.

PMID- 9561099
TI  - Mitogen-activated protein kinases and endothelial prostacyclin secretion.

PMID- 9561100
TI  - Crosstalk between elevation of [Ca2+]i, reactive oxygen species generation and
      phospholipase A2 stimulation in a human keratinocyte cell line.
AB  - The aim of the study was to explore the possible interrelationship between
      reactive oxygen species (ROS) formation and cPLA2 activation and the mediator
      role that [Ca2+]i may play in these processes in the human keratinocyte cell
      line, HaCaT. HaCaT cells can be invoked to transiently produce ROS by epidermal
      growth factor (EGF), thapsigargin (TPG) and the Ca(2+)-ionophore, A23187. These 3
      agonists transiently increase [Ca2+]i with characteristic kinetics and magnitude.
      TPG and A23187 each activates on its own [3H]AA release from prelabeled cells,
      whereas EGF on its own has no effect on [3H]AA release. However, EGF augments
      [3H]AA release invoked by TPG or A23187 several fold. EGF activates MAP kinase
      cascades in HaCaT cells, leads to ROS formation and induces relatively small (1.6
      fold) elevation in [Ca2+]i, whereas A23187 and TPG lead to a substantial
      elevation in [Ca2+]i (2.5 to 5 fold) and to ROS formation. Both have a minor
      effect on MAP kinase activation. The synergism in PLA2 activation by EGF and TPG
      or A23187, and the sensitivity of [3H]AA release to N-acetylcysteine (NAC) and
      dithiothreitol (DTT) (potent reducing agents) or to DPI (an inhibitor of FAD
      dependent oxidases) lead to the suggestion that ROS formation, elevation of
      [Ca2+]i and PLA2 activation are causally related. Since we show that elevation of
      [Ca2+]i is a prerequisite for both ROS and PLA2 activation, it is possible that
      these processes contribute to the toxicity (apoptosis) exerted by chronic
      elevation of [Ca2+]i.

PMID- 9561101
TI  - Cloning, tissue-specific expression and regulation of the bovine thromboxane A2
      receptor.

PMID- 9561102
TI  - Weak inhibitors of cyclooxygenases may exert their antinociceptive effect by
      modulation of transcription factors.

PMID- 9561104
TI  - Biosynthesis of novel divinyl ether oxylipins by enzyme from garlic (Allium
      sativum L.) bulbs.

PMID- 9561103
TI  - New group of lipid mediators containing omega-hydroxyarachadonic acid (20-HETE).

PMID- 9561105
TI  - Catalytic and spectroscopic properties of linoleate diol synthase of the fungus
      Gaumannomyces graminis.

PMID- 9561106
TI  - Avenoleic acid: a new oxylipin from oat seeds.

PMID- 9561107
TI  - Discovery of novel cannabinoid receptor ligands from diverse marine organisms.

PMID- 9561108
TI  - Accumulation of platelets as a key mechanism of human erection. A scintigraphic
      study in patients with erectile dysfunction receiving intracavernous injection of
      PGE1, papaverine/phentolamine.

PMID- 9561109
TI  - Can self-injection therapy cure impotence?

PMID- 9561110
TI  - Cytokine levels in five different fluid compartments during amniotic fluid
      infection and labour.

PMID- 9561111
TI  - Characterization of A-93178, an iminoxy-quinoline inhibitor of leukotriene
      biosynthesis.

PMID- 9561112
TI  - Transcellular synthesis of Cys-LT: from isolated cells to complex organ system.

PMID- 9561113
TI  - Leukotriene D4-induced signalling events in human epithelial cells: G alpha i3
      activation and translocation.
AB  - Our model of LTD4-induced signal transduction in epithelial cells is summarised
      in Figure 2. Extending what is already known about LTD4 signalling in epithelial
      cells, we identified the Gi3-protein as the crucial PTX sensitive G-protein and
      found that it is translocated to what might be a cytoskeletal fraction. This
      finding suggests a subtle response to LTD4, mediated via the bifurcation at the
      alpha/beta gamma junction. Although little is known about the role of epithelial
      cells in inflammation, it has been shown that such cells produce the potent
      chemoattractant LTB4 and the proinflammatory 5-HETE in response to intracellular
      accumulation of Ca2+ 24. The target protein(s) and the effect(s) of the
      translocation of the activated G alpha i3-proteins, as well as the possible role
      of the beta/gamma-subunits of Gi3, remain to be elucidated.

PMID- 9561114
TI  - Interactions of renal cytochrome P450 (CYP), angiotensin (AII) and tumor necrosis
      factor-alpha (TNF): implications for ion transport.

PMID- 9561115
TI  - Modulation of leukocyte-endothelial cell interaction and leukotriene dependent
      vasoconstriction by prostacyclin mimetics in the isolated rabbit heart.

PMID- 9561116
TI  - Improvement of renal function with selective thromboxane A2 synthetase inhibitor,
      DP-1904 in lupus nephritis.

PMID- 9561117
TI  - Characterization of the prostaglandin EP3-receptor from porcine heart.

PMID- 9561118
TI  - Bisallylic hydroxylation of linoleic and arachidonic acids by adult and fetal
      human liver microsomes and a comparison with human recombinant cytochromes P450.

PMID- 9561119
TI  - Organization of the human prostacyclin synthase gene and association analysis of
      a novel CA repeat in essential hypertension.

PMID- 9561120
TI  - Mechanism of action of anti-inflammatory drugs.

PMID- 9561122
TI  - In vivo measurement of interstitial TxB2-concentrations in skeletal muscle during
      ischemia and reperfusion.

PMID- 9561121
TI  - Differential effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of
      prostaglandin-H synthase isoenzymes in mouse tissues.

PMID- 9561123
TI  - Mutation of Tyr-383 in leukotriene A4 hydrolase: effects on enzyme activities.

PMID- 9561124
TI  - Prostaglandin receptors of the EP2 and EP4 subtypes regulate B lymphocyte
      activation and differentiation to IgE-secreting cells.

PMID- 9561125
TI  - Urinary 9 alpha, 11 beta-PGF2 as a marker of mast cell activation in allergic and
      aspirin-intolerant asthma.

PMID- 9561126
TI  - Induction of nitric oxide synthase (NOS) and vascular endothelial growth factor
      (VEGF) in experimental model of angioplasty and heart ischemia.

PMID- 9561127
TI  - CGP57698: a structurally simple, highly potent peptido-leukotriene (pLT)
      antagonist of the quinoline type.

PMID- 9561128
TI  - S 18886, a new thromboxane (TP)-receptor antagonist is the active isomer of S
      18204 in all species, except in the guinea-pig.

PMID- 9561130
TI  - Prostaglandin E2 downregulates inducible nitric oxide synthase expression in
      microglia by increasing cAMP levels.

PMID- 9561129
TI  - Glial and neuronal expression of cyclooxygenase-2: relevance to Alzheimer's
      disease.

PMID- 9561131
TI  - Formation of a novel class of F3-isoprostanes during peroxidation of
      eicosapentaenoic acid (EPA).

PMID- 9561132
TI  - Plasma 8-epi PGF2 alpha levels in health and disease.

PMID- 9561133
TI  - Regulation of MAP-kinase activation by 8-iso-prostaglandin F2a in cultured rat
      aortic smooth muscle cells.

PMID- 9561134
TI  - The effect of non-prostanoid prostacyclin mimetics on cyclic AMP production by
      neuronal SK-N-SH cells.

PMID- 9561135
TI  - Biosynthesis of 2-arachidonoyl-glycerol, a novel cannabimimetic eicosanoid, in
      mouse neuroblastoma cells.

PMID- 9561136
TI  - Hyperalgesia-associated spinal synthesis and release of prostaglandins.

PMID- 9561137
TI  - Functional consequences of the identification and localisation of cyclooxygenase
      isoforms in dorsal horn of rat spinal cord.

PMID- 9561138
TI  - Cyclooxygenase-2 in the spinal cord: localization and regulation after a
      peripheral inflammatory stimulus.
AB  - Prostaglandins are known as mediators in spinal nociceptive processing after
      peripheral inflammation. Cyclooxygenase isozymes Cox-1 and Cox-2 as enzymes
      essential for prostaglandin biosynthesis were therefore investigated in rat
      spinal cord. mRNA and protein of both enzymes was detected in cervical and lumbar
      sections of the spinal cord of normal animals. Enzyme activity of Cox-1 and Cox-2
      could be determined by the use of specific inhibitors. Cox-2-immunoreactivity
      (IR) was found in the spinal cord of untreated rats in neurons of laminae II-III,
      motoneurons of lamina IX and in glial cells. Most prominent staining was observed
      in the nuclear envelope. Under an acute peripheral inflammatory stimulus a
      transient 2-fold increase in Cox-2 mRNA was noticed bilaterally in the lumbar
      spinal cord by reverse transcription-polymerase chain reaction. This increase was
      reflected on a smaller scale at protein levels in Western blot analysis of spinal
      membrane preparations. In the chronic state of adjuvant-induced arthritis, Cox-2
      levels were raised again significantly. Cox-2 might therefore be regarded as the
      Cox isozyme responsible for increased spinal prostanoid release in nociceptive
      processing under peripheral stimulation.

PMID- 9561139
TI  - The production of biologically active eicosanoids by yeasts.

PMID- 9561140
TI  - Is lipoxygenation of pathogen-derived arachidonic acid involved in plant
      protection?

PMID- 9561141
TI  - The production of eicosanoid precursors by mucoralean fungi.

PMID- 9561142
TI  - Biotransformation of arachidonic acid and other eicosanoids by the yeast
      Dipodascopsis uninucleata, the oomycete fungi Saprolegnia diclina and Leptomitus
      lacteus and the zygomycete fungus Mortierella isabellina.

PMID- 9561143
TI  - Human prostacyclin receptor: cloning and co-expression with EP3 prostaglandin
      receptor.

PMID- 9561144
TI  - Three isoforms of the prostaglandin E receptor EP3 subtype different in agonist
      independent constitutive Gi activity and agonist-dependent Gs activity.

PMID- 9561145
TI  - Neurogenic inhibitory action through platelets of platelet activating factor
      (PAF) on vasoconstrictive responsiveness to pressor agents.

PMID- 9561146
TI  - High and low affinity mutants of platelet-activating factor receptor.

PMID- 9561147
TI  - Differential effect of corticotropin releasing factor on interleukin-1 alpha and
      interleukin-1 beta-induced prostaglandin synthesis in endothelial cells and
      fibroblasts.

PMID- 9561148
TI  - Brain and peripheral anandamide amidohydrolase and its inhibition by synthetic
      arachidonate analogues.

PMID- 9561149
TI  - Effects of 13-HODE and other momohydroxides on integrin/ligand binding:
      implications for cell cell interactions.

PMID- 9561150
TI  - Effect of linoleic acid supplements on vessel wall hyperplasia in rabbits.

PMID- 9561151
TI  - Effects of linoleic acid and/or marine fish oil supplements on vessel wall
      thromboresistance in patients undergoing cardiac surgery.

PMID- 9561152
TI  - 13-Hydroxyoctadecadienoic acid reverses epidermal hyperproliferation via
      selective inhibition of membrane protein kinase C-beta activity.

PMID- 9561154
TI  - The importance of linoleic acid metabolites in cancer metastasis and in the
      synthesis and actions of 13-HODE.
AB  - Large scale human epidemiological studies indicate that high intakes of linoleic
      acid protect against the development of cancer. One mechanism may be the
      generation of 13-HODE from linoleic acid. 13-HODE prevents cell adhesion to
      endothelial cells and can inhibit cancer metastasis. 13-HODE synthesis is
      enhanced by cyclic AMP. Gamma-linolenic acid, a desaturated metabolite of
      linoleic acid, causes substantial stimulation of 13-HODE synthesis. A fall in
      gamma-linolenic acid synthesis with age may be related to the age-related fall in
      13-HODE formation.

PMID- 9561153
TI  - Effects of linoleic acid supplements on atopic dermatitis.

PMID- 9561156
TI  - Mice lacking 5-lipoxygenase have increased cortical bone thickness.

PMID- 9561155
TI  - The role of prostaglandins and nitric oxide in the response of bone to mechanical
      stimulation.

PMID- 9561157
TI  - Parathyroid hormone induction of cyclooxygenase-2 expression in human osteoblasts
      depends on both cyclic AMP and calcium-dependent pathways.

PMID- 9561159
TI  - Mechanotransduction in bone cells: induction of nitric oxide and prostaglandin
      synthesis by fluid shear stress, but not by mechanical strain.

PMID- 9561158
TI  - Involvement of prostaglandin endoperoxide H synthase-2 in osteoclast formation
      induced by parathyroid hormone.
AB  - Prostaglandin (PG)E2 is one of the most important endogenous bone resorbing
      factors. In the previous study, we demonstrated that osteoclast formation induced
      by IL-1 beta was mediated by PGE2 produced by induced prostaglandin endoperoxide
      H synthase-2 (PGHS-2) in osteoclastic cells. In the same bone marrow culture
      system, indomethacin also suppressed the osteoclast formation induced by PTH. The
      inhibition was abolished by exogenously added PGE2 at dose as low as 3 x 10(-9)
      M, which was too low to elevate the intracellular cAMP and calcium levels and
      also it was too low to cause osteoclast formation by itself. In order to estimate
      what kind of cell produced such small amount of PGE2 in the PTH treatment, we
      carried out antibody staining of PGHS-1&PGHS-2 and PGHS activity in the intact
      bone marrow cells. PTH was found to induce PGHS activity in tartrate-resistant
      acid phosphatase (TRACP) positive mononuclear cells and the PGHS activity was
      inhibited by NS-398, a specific inhibitor of PGHS-2. Immunocytochemical staining
      supported the expression of PGHS-2 in TRACP-positive mononuclear cells. These
      findings suggest that PGHS-2 induced by PTH may regulate osteoclast formation by
      different mechanism from that induced by IL-1 beta.

PMID- 9561160
TI  - Histamine potentiates leukotriene B4-induced leukocyte adhesion: a potential role
      of histamine1-receptor antagonism in allergic leukocyte recruitment.

PMID- 9561161
TI  - Gastric prostacyclin (PGI2) prevents stress-induced gastric mucosal injury in
      rats by inhibiting leukocyte activation.

PMID- 9561162
TI  - Anti-P-selectin antibody exacerbated inflammatory responses in acetic acid
      induced colitis.

PMID- 9561163
TI  - Heterogeneous distribution of COX-2 over-expression in human colon carcinoma
      cells.

PMID- 9561164
TI  - Hsp70: a subunit of the cytosolic 12(S)-HETE binding complex.

PMID- 9561165
TI  - Apoptosis induction and inhibition of colon-26 tumour growth and angiogenesis:
      findings on COX-1 and COX-2 inhibitors in vitro & in vivo and topical diclofenac
      in hyaluronan.

PMID- 9561167
TI  - Prostaglandin D synthase, beta-trace and sleep.

PMID- 9561166
TI  - Phospholipase A2 inhibitory activity in lung cancer cell lines.

PMID- 9561168
TI  - Human beta-trace in normal and pathological CNS tissues, genital organs and body
      fluids.
AB  - The function of BTP is still unknown. In CNS, the high amount of BTP in the white
      CNS matter and the glial cells as well as in genital organs of the stroma of
      epididymis suggest that BTP has a supportive function. Slight evidence of a
      synthesis in patients with MS and slightly increased CSF values in stroke
      patients may suggest that BTP is involved in repair mechanism of damaged brain
      tissue, or may be related from destroyed brain tissue. In samples of CSF,
      determination of BTP could be of value as differentiating glial cell tumors from
      tumors of other kinds, as well as the recently suggested diagnostic value of the
      Creutzfeldt-Jakob disease (20). However, also other functions of BTP has been
      suggested. (21, 22).

PMID- 9561169
TI  - Effect of immunization with beta-trace protein on testosterone levels in animals.

PMID- 9561170
TI  - Eicosanoids mediate insect cellular immune reactions to bacterial infections.

PMID- 9561171
TI  - Arachidonic acid and eicosanoids in Hydra: possible endogenous signals involved
      in chemoreception and modulation of the feeding behaviour.

PMID- 9561172
TI  - Synthesis and action of eicosanoids in warm and cold-acclimated amphibians.

PMID- 9561173
TI  - Molecular and catalytic properties of mammalian lipoxygenases compared with
      soybean lipoxygenase-1.

PMID- 9561174
TI  - Leukotriene A4 hydrolase activity in Xenopus laevis.

PMID- 9561175
TI  - Monocyte binding to endothelial cells induced by oxidized phospholipids present
      in minimally oxidized low density lipoprotein is inhibited by a platelet
      activating factor receptor antagonist.
AB  - Our group has previously demonstrated that oxidized phospholipids derived from
      mildly oxidized low density lipoprotein (MM-LDL) or oxidized 1-palmitoyl-2
      arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) increase monocyte
      endothelial interactions. There are indications that the effects of these
      phospholipids are receptor mediated. Oxidized phospholipids have previously been
      shown to activate cells via the platelet activating factor (PAF) receptor,
      therefore, we pretreated human aortic endothelial cells (HAECs) with a PAF
      receptor antagonist (WEB 2086) prior to treatment with oxPAPC. WEB 2086 inhibited
      monocyte binding to endothelial cells induced by oxPAPC (200 micrograms/ml) at
      concentrations from 1 nM to 10 microM, but had no effect on the induction of
      monocyte binding induced by lipopolysaccharide (LPS). We were able to isolate and
      identify several active oxidized phospholipids by combined normal phase high
      performance liquid chromatography (HPLC) and electrospray mass spectrometry
      (LC/MS). The induction of monocyte binding to HAECs by two of these partially
      purified phospholipids was totally abolished by the pretreatment of HAECs with
      WEB 2086 (100 nM). PAF itself, however, when tested at concentrations from 10 nM
      to 10 microM had no effect on monocyte binding. These results suggest that
      several of the oxidized phospholipids present in MM-LDL and oxPAPC induce
      monocyte binding through a receptor which is perhaps distinct from the PAF
      receptor, but can be blocked by the PAF-receptor antagonist WEB 2086.

PMID- 9561176
TI  - Regulation of 5-lipoxygenase activity by selenium-dependent peroxidases-effects
      of transforming growth factor-beta and 1,25-dihydroxyvitamin D3.

PMID- 9561177
TI  - Thromboxane A2 potentiates thrombin-induced proliferation of coronary artery
      smooth muscle cells.
AB  - The activation of thrombin is the key event in clot formation after vascular
      injury. Thrombin itself, but also other clot-derived factors, such as thromboxane
      A2 (TXA2), are mitogenic for vascular smooth muscle cells. We have studied the
      possible interactions between thrombin and TXA2 in stimulation of coronary artery
      smooth muscle cell (SMC) proliferation. Thrombin (1 U/ml) caused a significant
      proliferatory response in SMC. U 46619, a stable TXA2 mimetic, had only a minor
      stimulating effect by its own but markedly potentiated the thrombin-induced
      mitogenesis. A possible mechanism for these potentiating effects is provided by
      the demonstration of a marked (6 fold) but transient (maximum after 20 min)
      increase in the expression of TXA2 receptor (TP receptor) mRNA in SMC by
      thrombin. Since a significant clot-related TXA2 generation was detected for at
      least 2 hours, the up-regulation of TP receptors by thrombin may represent a
      mechanism that is relevant for the in vivo situation of SMC proliferation after
      vessel injury.

PMID- 9561178
TI  - Isoforms of type-I 15-hydroxyprostaglandin dehydrogenase mRNA.

PMID- 9561179
TI  - Keratinocyte growth factor increases LTC4 synthesis and expression of flap in
      cultured rat alveolar type II cells.

PMID- 9561180
TI  - Type-I 15-hydroxyprostaglandin dehydrogenase: role in macrophage/osteoclast
      differentiation.

PMID- 9561181
TI  - PGE2 and TXA2 production by isolated macrophages from human placenta.

PMID- 9561182
TI  - Intrauterine eicosanoid production in uncomplicated and hypertensive pregnancies:
      alterations of placental 12-hydroxyeicosatetraenoic acid.

PMID- 9561183
TI  - Formation of cytochrome P450 metabolites of arachidonic acid by human placenta.

PMID- 9561184
TI  - Prostaglandin endoperoxide H synthase-2 expression in human amnion cells:
      involvement of tyrosine kinases in the regulation.

PMID- 9561186
TI  - The development of a highly specific, sensitive enzyme immunoassay for
      prostaglandin E1.

PMID- 9561185
TI  - Prostaglandin E2 production by endogenous secretion of interleukin-1 in decidual
      cells from term fetal membrane.

PMID- 9561187
TI  - The use of chemiluminescence to detect eicosanoids with greater speed and
      sensitivity.

PMID- 9561188
TI  - Vascular wall-rather than platelet PGE1-pretreatment in-vivo (but not in-vitro)
      decreases thrombogenicity.

PMID- 9561189
TI  - A model of arachidonic acid binding for 15-lipoxygenase.

PMID- 9561190
TI  - Changes in kinetic properties of cytosolic phospholipase A2 in activated rat
      neutrophils.

PMID- 9561191
TI  - Stimulation of PG I2-synthesis in the periodontal tissue by interleukin-1 alpha
      and -1 beta.

PMID- 9561192
TI  - Activation of cardiac EP3 receptors by PGE1 reduces beta-adrenergic inotropic
      effects.

PMID- 9561193
TI  - The aspartic proteinases. An historical overview.

PMID- 9561194
TI  - The regulation of sequential processing of HIV-1 Gag by the viral protease.

PMID- 9561195
TI  - A cellular anti-apoptosis protein is cleaved by the HIV-1 protease.
AB  - Cleavage of non-viral proteins is rarely observed with the HIV-1 protease (HIV
      pr). One such cleavage event occurs with bcl-2, an important cytoprotective
      protein. The loss of bcl-2 has biological consequences, leading to enhanced HIV
      replication and programmed death of the host cell. A strategy is proposed to
      suppress HIV with non-cleavable mutants of bcl-2.

PMID- 9561196
TI  - Engineering catalytically defective forms of HIV protease to modulate its
      activity.

PMID- 9561197
TI  - The aspartic proteinase from equine infectious anaemia virus.

PMID- 9561198
TI  - The effect of substrates on the kinetics and the in vivo threshold activity of
      mutant HIV-1 proteases.

PMID- 9561199
TI  - A comparison of gag-pol precursor cleavage in naturally arising HIV variants.

PMID- 9561200
TI  - X-ray crystallographic studies of the structure-function relationships of HIV-1
      protease.

PMID- 9561201
TI  - Optimization of a macromolecular inhibitor of HIV-1 protease.

PMID- 9561202
TI  - In vitro selection and characterization of VX-478 resistant HIV-1 variants.
AB  - VX-478 (141W94), a potent inhibitor of HIV protease, is in late stage clinical
      trials for the treatment of HIV infection and AIDS. Resistant viruses were raised
      in vitro by passage of HIV-1IIIB in the presence of increasing concentrations of
      VX-478 and the related hydroxyethylamino sulfonamide inhibitor VB-11,328. By
      direct PCR analysis of selected viruses, a number of mutations were identified
      (L10F, M46I, I47V, I50V and I84V) in the protease gene. These mutations were
      introduced into recombinant HIV-1 protease and the mutant enzymes assayed against
      a panel of inhibitors of diverse chemical structure. For VX-478, significant
      increases in IC90 and Ki were observed for virus or protease, respectively,
      containing I50V single mutation or an M46I/I47V/I50V triple mutation. The mutant
      proteases were also characterized for their kinetic competence to process
      substrates representing cleavage sites of gag-pol viral polypeptide. The kinetic
      data were interpreted with the aid of molecular modeling to understand the effect
      of mutations on inhibitor binding and processing of the gag-pol polypeptide to
      generate infective virions.

PMID- 9561203
TI  - Sensitivity to inhibition and catalytic efficiency of HIV proteinase mutants.

PMID- 9561205
TI  - Investigation of an allosteric site of HIV-1 proteinase involved in inhibition by
      Cu2+.

PMID- 9561204
TI  - Computer assisted evaluation of inhibitor sensitivity to HIV-1 PR mutants.

PMID- 9561206
TI  - Analysis of autoprocessing of Mason-Pfizer monkey virus proteinase in vitro.
      Three active forms of proteinase.

PMID- 9561207
TI  - Subsequent selfprocessing of bovine leukemia virus proteinase in vitro.

PMID- 9561208
TI  - Mechanism of action of aspartic proteases.

PMID- 9561209
TI  - Theory and method of a priori computation of catalytic acts of aspartic and
      serine proteinases.

PMID- 9561210
TI  - Comparison of the specificity of the aspartic proteinases towards internally
      consistent sets of oligopeptide substrates.

PMID- 9561211
TI  - Expression of chimeric human aspartic proteinases.

PMID- 9561212
TI  - Cathepsin E. The best laid plans of mice and men.

PMID- 9561214
TI  - An aspartic proteinase expressed in the equine placenta.
AB  - This manuscript describes the cloning of a novel aspartic proteinase expressed in
      the placenta of the horse (order Perrisodactyla). Evidence for similar genes in
      the cat (Carnivora) and ruminants (Artiodactyla), indicates that these molecules
      have been conserved within widely divergent species with distinct types of
      placentation. Since ePAG is produced by the outer cell layer (trophoblast) of the
      placenta, it can tentatively be grouped with the pregnancy-associated
      glycoproteins (PAG) of cattle, sheep, and pig. The high sequence identity that
      ePAG shares with pepsinogens as well as the PAG, indicates that ePAG may be the
      evolutionary bridge that links these two groups of aspartic proteinases.

PMID- 9561213
TI  - Biosynthesis and intracellular targeting of the lysosomal aspartic proteinase
      cathepsin D.

PMID- 9561215
TI  - Protein engineering aspartic proteinases. Site-directed mutagenesis, biochemical
      characterisation, and X-ray analysis of chymosins with substituted single amino
      acid substitutions and loop replacements.

PMID- 9561216
TI  - Post X-ray crystallographic studies of chymosin specificity. The role of
      histidine-proline cluster of kappa-casein in catalytic reactions.

PMID- 9561217
TI  - Epitope mapping of recombinant human procathepsin D.

PMID- 9561218
TI  - Construction of chimeric enzymes to probe subsite contributions to catalytic
      specificity.

PMID- 9561219
TI  - Expression of multiple genes for pregnancy-associated glycoproteins in the sheep
      placenta.
AB  - Together these experiments have showed that there are many PAG genes in the ovine
      genome and many of these are expressed in the placenta. These PAG genes vary as
      much as 40% in nucleotide sequence identity. Thus, a wide range of ovPAG
      molecules are secreted at the placental-uterine surface during pregnancy.

PMID- 9561220
TI  - Mass spectrometry as a tool for studying the action of human aspartic proteases
      on peptides and proteins.

PMID- 9561221
TI  - Skin surface proteolytic activity. Partial characterization and identification.
AB  - Skin surface proteolytic activity in the living animal was determined by a
      sensitive, non-invasive methodology developed in our laboratory. A non-leaky well
      was constructed on the shaved back of an anesthetized guinea pig. The well
      contained the reaction mixture including the substrate 125I-S-carboxymethylated
      insulin B-chain (ICMI). The proteolytic activity was shown to be time-dependent.
      The activity was strongly inhibited by pepstatin A, indicating the involvement of
      aspartic proteinase(s) such as cathepsin D and/or E. Pretreatment of the skin
      with propylene glycol blocked the proteolytic activity. The present study
      demonstrates the presence of proteolytic activity located on skin surface using a
      unique, non-invasive method for in situ proteinase determination in the living
      animal.

PMID- 9561222
TI  - Cathepsin E in the central nervous system.

PMID- 9561223
TI  - Detailed analysis of human cathepsin E prime region specificity.

PMID- 9561224
TI  - Proteolytic and non-proteolytic activation of prorenin.

PMID- 9561225
TI  - The roles of the basic residues in the prosegment of aspergillopepsinogen I.

PMID- 9561226
TI  - Activation mechanism of pepsinogen as compared to the processing of HIV protease
      gag-pol precursor protein.

PMID- 9561227
TI  - Cardosinogen A. The precursor form of the major aspartic proteinase from cardoon.

PMID- 9561228
TI  - Crystal structure of human pepsinogen A.

PMID- 9561229
TI  - Crystallographic studies of an activation intermediate of human gastricsin.

PMID- 9561230
TI  - Aspergillus niger acid proteinase A. Structure and function.

PMID- 9561231
TI  - Crystal structure of the Rhizomucor miehei aspartic proteinase.

PMID- 9561232
TI  - Rhizomucor miehei aspartic proteinases having improved properties.

PMID- 9561233
TI  - Structure of secreted aspartic proteinases from Candida. Implications for the
      design of antifungal agents.
AB  - Pathogens of the genus Candida can cause life threatening infections in immuno
      compromised patients. The three-dimensional structures of two closely related
      secreted aspartic proteinases from C. albicans complexed with a potent (Ki = 0.17
      nM) inhibitor, and an analogous enzyme from C. tropicalis reveal variations on
      the classical aspartic proteinase theme that dramatically alter the specificity
      of this class of enzymes. The novel fungal proteases present: i) an 8 residue
      insertion near the first disulfide (Cys45-Cys50, pepsin numbering) that results
      in a broad flap extending towards the active site; ii) a seven residue deletion
      replacing helix hN2 (Ser110-Tyr114), which enlarges the S3 pocket; iii) a short
      polar connection between the two rigid body domains that alters their relative
      orientation and provides certain specificity; and i.v.) an ordered 12 residue
      addition at the carboxy terminus. The same inhibitor (A-70450) binds in an
      extended conformation in the two variants of C. albicans protease, and presents a
      branched structure at the P3 position. However, the conformation of the terminal
      methylpiperazine ring is different in the two crystals structures. The
      implications of these findings for the design of potent antifungal agents are
      discussed.

PMID- 9561235
TI  - Bacterial aspartic proteinases as novel antibiotic targets.

PMID- 9561234
TI  - Yapsin1. Structure, biosynthesis, and specificity.

PMID- 9561236
TI  - Structural thermodynamic study of the binding of renin inhibitors to
      endothiapepsin.

PMID- 9561237
TI  - Development and testing of inhibitors of Candida aspartic proteinases.

PMID- 9561238
TI  - Primary substrate specificities of secreted aspartic proteases of Candida
      albicans.

PMID- 9561239
TI  - Functional aspects of secreted Candida proteinases.

PMID- 9561240
TI  - Substrate specificity of non-pepsin-type acid proteinase, Aspergillus niger
      proteinase A.

PMID- 9561241
TI  - Pepstatin-insensitive carboxyl proteinases from prokaryotes. Catalytic residues
      and substrate specificities.

PMID- 9561242
TI  - Overcoming the unfavourable entropic contribution of ligand binding with a
      macrocyclic inhibitor bound to penicillopepsin.

PMID- 9561243
TI  - Structural analysis of plasmepsin II. A comparison with human aspartic proteases.

PMID- 9561244
TI  - Screening aspartyl proteases with combinatorial libraries.
AB  - Large numbers of pharmaceutically relevant low-molecular weight compounds can now
      be synthesized using combinatorial methods. Screening these large libraries of
      compounds requires high throughput assays. These methods are utilized to search
      for inhibitors of the aspartyl proteases, plasmepsin II and cathepsin D.
      Plasmepsin II, a protease found in the malaria parasite, hydrolyzes human
      hemoglobin, the nutrient source for the parasite and is a new target for anti
      malaria therapy. Cathepsin D may be involved in many biological processes and
      inhibitors would help to clarify the role of cathepsin D in these processes.
      Plasmepsin II and cathepsin D are approximately 35% identical in amino acid
      sequence. Therefore, a comparison of the screening results of these two enzymes
      will be very useful in determining each enzyme's specificity and demonstrating
      the power of utilizing encoded combinatorial libraries.

PMID- 9561245
TI  - Thermodynamics and proton uptake for pepstatin binding to retroviral and
      eukaryotic aspartic proteases.

PMID- 9561246
TI  - Expression, purification, and characterization of the recombinant pepsin
      inhibitor from Ascaris suum.

PMID- 9561247
TI  - X-ray crystallographic studies of the complex between porcine pepsin and the
      aspartic proteinase inhibitor PI-3 from the nematode Ascaris suum.

PMID- 9561248
TI  - Studies on plasmepsins I and II from the malarial parasite Plasmodium falciparum
      and their exploitation as drug targets.

PMID- 9561249
TI  - Plasmepsins I and II from the malarial parasite Plasmodium falciparum.

PMID- 9561250
TI  - Molecular cloning of aspartic proteinases from flowers of Cynara cardunculus
      SUBSP. flavescens CV. cardoon and Centaurea calcitrapa.

PMID- 9561251
TI  - Aspartic proteinases and inhibitors in plant pathogenesis.

PMID- 9561252
TI  - Acid proteinase from Nepenthes distillatoria (Badura).

PMID- 9561253
TI  - A comparative study on the aspartic proteinases from different species of Cynara.

PMID- 9561254
TI  - An aspartic proteinase from flowers of Centaurea calcitrapa. Purification,
      characterization, molecular cloning, and modelling of its three-dimensional
      structure.

PMID- 9561255
TI  - Substrate specificity and molecular modelling of aspartic proteinases (cyprosins)
      from flowers of Cynara cardunculus subsp. flavescens cv. cardoon.

PMID- 9561256
TI  - Improved diagnosis of breast implant rupture with sonographic findings and
      artificial neural networks.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the use of sonographic findings
      combined with artificial neural networks as an aid to the diagnosis of breast
      implant rupture. MATERIALS AND METHODS: From a database of 78 breast implants
      that were evaluated prospectively with sonography and then surgically removed,
      sonographic findings and surgical results were used to train and test
      backpropagation and radial basis function artificial neural networks by using the
      leave-one-out method. Receiver operating characteristic (ROC) curve analysis was
      used to compare the performance of the different neural networks with that of the
      radiologists involved. RESULTS: By using the ROC area index as a measure of
      performance, the artificial neural network (Az = 0.8744) outperformed the
      radiologists (Az = 0.8057), although not by a statistically significant
      difference (P = .09). The best-performing network used, in addition to the
      sonographic findings, the diagnosis of the radiologist as an input. This network
      (Az = 0.9245) outperformed both the radiologists and the "unaided" networks by a
      statistically significant margin (P = .02 for radiologists, P = .04 for the
      unaided network). The network performed remarkably well in those cases in which
      the radiologists classified the implant as indeterminate, predicting the correct
      diagnosis in 23 of 25 cases (92%). CONCLUSION: The results suggest that
      artificial neural networks in tandem with the unaided radiologic diagnosis can
      improve the accuracy rate in the detection of implant rupture based on
      sonographic findings. This "team" approach provided the best results.

PMID- 9561257
TI  - Automated lung segmentation in digitized posteroanterior chest radiographs.
AB  - RATIONALE AND OBJECTIVES: The authors developed and tested a gray-level
      thresholding-based approach to automated lung segmentation in digitized
      posteroanterior chest radiographs. MATERIALS AND METHODS: Gray-level histogram
      analysis was initially performed to establish a range of thresholds for use
      during an iterative global gray-level thresholding technique. Local gray-level
      threshold analysis was then performed on the output of global thresholding. The
      resulting contours were subjected to several smoothing processes, including a
      rolling-ball technique. The final contours closely approximated the boundaries of
      the aerated lung regions. The method was applied to a database of 600
      posteroanterior chest images. Radiologists rated the accuracy and completeness of
      the contours with a five-point scale. RESULTS: Results of the subjective rating
      evaluation indicated that this method was accurate, with 79% of the assigned
      ratings reflecting moderately or highly accurate segmentation and only 8% of the
      ratings indicating moderately or highly inaccurate segmentation. CONCLUSION: This
      gray-level thresholding-based approach provides accurate automated lung
      segmentation in digital posteroanterior chest radiographs.

PMID- 9561258
TI  - Fine needle aspiration biopsy of the breast: importance of benign, nonspecific
      results.
AB  - RATIONALE AND OBJECTIVES: The authors attempted to determine the importance of
      benign but nonspecific findings from an adequate sample obtained with image
      guided, fine-needle aspiration biopsy (FNAB) of the breast. MATERIALS AND
      METHODS: Four hundred thirty-seven image-guided FNAB specimens obtained over a 4
      year period were reviewed. Pathologic results, mammograms, sonograms, and
      radiology reports were correlated for all cases described as benign but
      nonspecific on the basis of cytologic results. Lesion characterization, type of
      imaging, and targeting accuracy were assessed. Follow-up method (imaging and/or
      clinical follow-up, core biopsy, open biopsy) was determined. RESULTS: Of the 427
      lesions, 99 (23%) were designated benign but nonspecific. In 75 of the cases,
      biopsy (core or open) had been performed or there had been at least 2 years of
      follow-up at the time of this study. Of these, 32 lesions were benign on the
      basis of follow-up, 27 (36%) were benign at secondary biopsy, seven (9%) were
      malignant at final biopsy, and nine (12%) were lost to follow-up. Five of the
      seven cancers occurred in the 1st year of the study; these lesions were sampled
      for biopsy based on their mammographic appearance. The lesions in an additional
      24 patients were benign after at least 1 year of follow-up. CONCLUSIONS: Benign,
      nonspecific imaged-guided FNAB results are reliable if targeting is accurate and
      if the mammographic findings support a benign process.

PMID- 9561259
TI  - Pulsatile cycle-specific data acquisition in carotid MR angiography with
      segmented FLASH sequence: experimental and clinical investigation.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the usefulness of diastolic data
      acquisition in magnetic resonance (MR) angiography of the carotid artery.
      MATERIALS AND METHODS: MR angiographic images of phantom models of 30%, 40%, and
      50% stenosis were obtained at different pulsatile cycles by using variable delay
      times from the electrocardiogram triggering with segmented fast low-angle shot
      sequences (14/7.3 [repetition time msec/echo time msec]) with k-space
      segmentation. The degree of stenosis was measured on the MR angiographic images
      by three observers. Poststenotic signal intensity loss was analyzed by measuring
      the signal intensity on the axial image acquired 10 mm distal to the stenotic
      portion of the 50% stenosis phantom at variable delay time from triggering. Six
      patients with stenosis of the internal carotid artery also underwent conventional
      and MR angiography. The degree of stenosis depicted on diastolic- and systolic
      phase MR angiographic images was measured by three observers and compared with
      that shown on the conventional angiographic images. RESULTS: The diastolic-phase
      images more accurately depicted the degree of stenosis than did the systolic
      phase images in the phantom and all six patients, although the degree of stenosis
      tended to be overestimated on both images. The degree of stenosis was most
      overestimated with triggering that occurred at the time of peak flow velocity. In
      the phantom with 50% stenosis, the signal intensity 10 mm distal to the stenotic
      portion was decreased in the systolic phase. CONCLUSION: Diastolic data
      acquisition is a useful method of reducing intra- and poststenotic signal
      intensity loss in the carotid artery.

PMID- 9561260
TI  - Fast spectroscopic imaging of water and fat resonances to improve the quality of
      MR images.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated whether fast spectroscopic
      imaging of water and fat resonances can produce high-quality anatomic magnetic
      resonance (MR) images of rodent tumors and human breast. MATERIALS AND METHODS:
      Fast MR spectroscopic images of eight rats with mammary tumors were acquired by
      using a 4.7-T MR unit equipped with self-shielded gradient coils. MR
      spectroscopic images of four human breasts were acquired with a 1.5-T MR unit.
      RESULTS: Artifacts due to eddy currents were minimal. Images synthesized from MR
      spectroscopic data, in which intensity was proportional to water signal peak
      height, were similar to T2-weighted MR images. Boundaries of rodent mammary
      tumors are similar but not identical on peak height-weighted and T2-weighted
      images. MR spectroscopic images of human breast showed improved detail compared
      to gradient-echo MR images. CONCLUSION: Preliminary results suggest that
      incorporation of fast MR spectroscopic imaging methods into many standard
      clinical MR imaging procedures may substantially improve image quality.

PMID- 9561261
TI  - Tips for getting a position with an independent private practice radiology group.

PMID- 9561262
TI  - Virtual colonoscopy: current status and future implications.

PMID- 9561263
TI  - Magnetic resonance angiography: a review.

PMID- 9561264
TI  - Fragmentary window filtering for multiscale lung nodule detection: preliminary
      study.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated computer-assisted diagnostic
      (CAD) methods used to detect suspicious areas on lung radiographs. MATERIALS AND
      METHODS: The authors designed a fragmentary window filtering (FWF) algorithm for
      detecting lung nodule patterns, which generally appear as circular areas of high
      opacity on the chest radiograph. The FWF algorithm helps differentiate circular
      patterns from overlapping radiographic background. A multiscale analysis was
      performed to locate multiscale nodules. Receiver operating characteristic
      analysis was performed by using a lung nodule that was extracted from a chest
      radiograph. The nodule underwent scalings and subsequent superimposition onto 140
      normal regions of interest from six chest radiographs. RESULTS: The FWF method
      was superior to the matched filtering method in the detection of suspicious
      areas. CONCLUSION: The proposed FWF-based method should provide improved
      detection of lung nodules on chest radiographs.

PMID- 9561265
TI  - Key effectors of signal transduction and G1 progression.

PMID- 9561266
TI  - p53 in tumor progression: life, death, and everything.

PMID- 9561267
TI  - Signal transduction through MAP kinase cascades.

PMID- 9561268
TI  - FHIT in human cancer.

PMID- 9561269
TI  - Phosphoinositide 4- and 5-kinases and the cellular roles of phosphatidylinositol
      4,5-bisphosphate.

PMID- 9561270
TI  - A diet with the right ingredients.

PMID- 9561271
TI  - Adhesion reduction as a new treatment innovation.
AB  - A new treatment option, an antiadhesion device, has proved effective in the
      reduction of postoperative adhesion formation and is now approved for use in the
      United States. The device is a thin, filmy membrane composed of two organic
      substances that are resorbed by the body. The device is inserted intraoperatively
      between apposing tissue surfaces that are potentially adhesiogenic. It proved
      effective in reducing the incidence of adhesions after both abdominal and pelvic
      surgery.

PMID- 9561273
TI  - Should do-not-resuscitate orders be suspended during surgical procedures?
AB  - One of the most controversial ethical dilemmas faced by perioperative nurses,
      surgeons, and anesthesia care providers is the do-not-resuscitate (DNR) order for
      a surgical patient. This article discusses informed consent, decision makers,
      laws and policy, DNR orders, and ethical considerations.

PMID- 9561272
TI  - The continuing ethical dilemma of the do-not-resuscitate order.
AB  - The continued use of the do-not-resuscitate (DNR) order remains very confusing to
      health care workers, especially when surgical intervention is undertaken either
      by choice or necessity. Although ethics committees can aid in clarification, and
      the use of advance directives can further define patient wishes, patient and
      family member education is necessary to ascertain what a surgical patient really
      desires. As technology advances, perioperative nurses will continue to be
      bombarded with ethical issues surrounding the DNR order. This article addresses
      how nurses can be proactive in obtaining answers to these difficult questions and
      learn how to deal with this dilemma.

PMID- 9561274
TI  - Cardiac anatomy and physiology: a review.
AB  - This article reviews the normal anatomy and physiology of the heart.
      Understanding the normal anatomic and physiologic relationships described in this
      article will help perioperative nurses care for patients who are undergoing
      cardiac procedures. Such knowledge also assists nurses in educating patients
      about cardiac procedures and about activities that can prevent, reverse, or
      improve cardiac illness.

PMID- 9561275
TI  - Perioperative nursing care when sudden patient death occurs in the OR.
AB  - This article explores how nurses cope with sudden death in the OR. It reviews the
      literature on this topic and explores grief and bereavement models, as well as
      provides a discussion of clinical coping methods identified through nursing
      experience. An education model presents information about implementing nursing
      care for the patient and family members. Critical care nursing research has been
      used to develop the model with adaptation to the perioperative setting. The model
      discusses the value of support for perioperative nurses and peers experiencing
      sudden patient death.

PMID- 9561276
TI  - Ultraclean laminar airflow ORs.
AB  - To minimize postoperative infections, ultraclean laminar airflow (LAF) units
      equipped with high-efficiency particulate air filters developed for electronic
      and aerospace technology have been adapted for ORs. Traditionally, the airflow
      was either vertical or horizontal and, to function properly, encompassed extra
      side walls inside the OR. Recently, new airstream technology has provided zoned
      down-flow units that provide an exponential airflow (i.e., resembling an upside
      down trumpet mouth). The exponential airflow allows for omission of extra side
      walls, making them more versatile in clinical use. Each different type of LAF
      requires knowledge of airstream patterns and how OR team members need to dress
      and work to prevent contamination of the sterile air and the aseptic areas. This
      article discusses different LAF systems and related demands on OR clothing and
      behavior.

PMID- 9561277
TI  - Can providing paging devices relieve waiting room anxiety?
AB  - The purpose of this study was to evaluate the effect of providing individuals who
      are waiting for surgical patients with digital pagers. Twenty-eight subjects
      received routine waiting room procedures, and 29 subjects were given digital
      pagers during surgical procedures. Subjects completed questionnaires concerning
      activity, state anxiety, and their perceived threat while patients were
      undergoing surgical procedures. The group that received the paging devices
      reported significantly greater state anxiety (i.e., P < .03) and a greater
      percentage of time spent outside surgical waiting rooms (i.e., P < .00) than the
      group that did not receive paging devices.

PMID- 9561278
TI  - Improving patient positioning for laparoscopic procedures.

PMID- 9561279
TI  - An abrupt zero-preoxygenation altitude threshold for decompression sickness
      symptoms.
AB  - INTRODUCTION: The altitude threshold for decompression sickness (DCS) symptoms
      has been variously described as being 18,000 ft (5,487 m) to above 25,000 ft
      (7,620 m). Safety and efficiency of aerospace operations require more precise
      determination of the DCS threshold. METHODS: Subjects were 124 males who were
      exposed to simulated altitudes (11 at 11,500 ft; 10 at 15,000 ft; 8 at 16,500 ft;
      10 at 18,100 ft; 10 at 19,800 ft; 20 at 21,200 ft; 20 at 22,500 ft; 10 at 23,800
      ft, and 25 at 25,000 ft) for 4 to 8 h. All breathed 100% oxygen beginning with
      ascent. Subjects were monitored for precordial venous gas emboli (VGE) and DCS
      symptoms. Probit curves representing altitude vs. incidence of DCS symptoms and
      VGE allowed estimation of respective risk. RESULTS: VGE were first observed at
      15,000 ft with increasing incidence at higher altitudes; over 50% at 21,200 ft
      and 70% or higher at 22,500 ft and above. The lowest altitude occurrence of DCS
      was a 5% incidence at 21,200 ft. At 22,500 ft, the DCS incidence abruptly climbed
      to 55%. CONCLUSION: A 5% threshold for DCS symptoms was concluded to be 20,500 ft
      under the conditions of this study. The abrupt increase in DCS symptoms, with
      zero-preoxygenation exposure above 21,200 ft implies a need for reconsideration
      of current USAF and FAA altitude exposure guidance.

PMID- 9561280
TI  - Alterations in muscular performance and orthostatic tolerance during Ramadan.
AB  - BACKGROUND: During Ramadan, physiological changes are expected to result from
      both long-term dietary restriction and partial sleep loss. HYPOTHESIS: We
      speculated that Ramadan fasting has deleterious effects on muscle performances
      and on orthostatic tolerance. METHODS: There were 11 senior fighter pilots tested
      on three occasions during the first week of Ramadan (Beg-R), during the fourth
      week (End-R) and during a control period, 2 mo after Ramadan (C). Each test
      session consisted of an assessment of the strength and endurance performances of
      the knee extensors and elbow flexors and of an analysis of the HR and BP
      responses to the orthostatic stress imposed by a 80 degrees head-up tilt.
      RESULTS: Body weight decreased by 2.7% at End-R in comparison with C period (p <
      0.01). Maximum isometric strength (MVC) of elbow flexor muscles decreased
      immediately (by 10-12%; p < 0.05). Muscular endurance at both 35 and 70% MVC were
      lower at End-R in comparison with C period (-28%, -22%, respectively; p < 0.05).
      The head-up tilt test at End-R was accompanied by a higher increase in heart
      response than during orthostasis during C and Beg-R periods, and by a decrease in
      pulse pressures (p < 0.001). These alterations in responses to the head-up tilt
      were associated with a fall by about 7% in plasma volume. CONCLUSIONS: These data
      demonstrate that Ramadan fasting leads to an impairment in muscular performances
      and to a decrease in orthostatic tolerance. Further studies are needed to verify
      the impact of these changes on +Gz tolerance.

PMID- 9561281
TI  - Red cell volume and [erythropoietin] responses during exposure to simulated
      microgravity.
AB  - In order to test the hypothesis that normal gravity is an important influence on
      human serum [Erythropoietin] ([Epo]), the hematologic response to 16 d of 6
      degrees head-down tilt (HDT, n = 6 men) was compared with 16 d of normal gravity
      exposure (CON, n = 7 men). Prior to bed rest, CON and HDT subjects, respectively,
      were similar in the following characteristics (mean +/- SD): age = 40 +/- 3, 39
      +/- 6 yr; height = 181 +/- 5, 182 +/- 6 cm; weight = 88.5 +/- 11.3, 81.7 +/- 12.0
      kg; maximal oxygen consumption in supine 6 degrees head-down tilt position
      (VO2max) = 2.63 +/- 0.38, 2.67 +/- 0.52 L.min-1; hematocrit = (Hct) 41.6 +/- 2.4,
      43.0 +/- 3.4%; hemoglobin ([Hb]) = 15.1 +/- 1.0, 14.5 +/- 1.0 g.100 ml-1; plasma
      volume (PV) = 3829 +/- 857, 3768 +/- 512 ml; and [Epo] = 11.6 +/- 2.9, 10.0 +/-
      6.2 mU.ml-1. Calculated red cell volume (RCV) was greater in HDT than CON (2845
      +/- 410 vs. 2139 +/- 253 ml, p < 0.05) at baseline. Decreases in PV (-15%, 580
      ml, p < 0.05) and an insignificant decrease in RCV (-12%, 354 ml, p = 0.07) were
      observed in the HDT group, with a concurrent 6% increase in [Hb] (p < 0.05). PV,
      RCV and [Hb] remained unchanged in the CON group. [Epo] remained unchanged during
      HDT (12.2 +/- 3.2; 10.8 +/- 3.8; 11.2 +/- 3.1; 11.2 +/- 2.6 mU.ml-1 for HDT days
      1, 2, 8 and 16, respectively). There was no difference between CON and HDT groups
      in [Epo] before or during HDT. It was concluded that the insignificant change (
      12%) in RCV observed during HDT was insufficient to stimulate an increase in
      [Epo], probably because the content of oxygen in arterial blood remained
      unaffected. The observation that [Epo] remained unchanged despite this loss of
      RCV during HDT also suggests a possible decrease in the responsiveness of the
      erythropoietic system to [Epo].

PMID- 9561282
TI  - Evolved gas, pain, the power law, and probability of hypobaric decompression
      sickness.
AB  - The intensity of a pain-only decompression sickness (DCS) symptom with respect to
      time at altitude increases, peaks, and then declines in some cases. A similar
      pattern is also seen in a graph of the probability density function [f(t)] for
      DCS. The f(t) is the proportion of DCS per unit time with respect to time at
      altitude. The integration of f(t) with respect to time provides the cumulative
      probability of DCS [P(DCS)]. We suspect that the perceived intensity of pain with
      a given stimulus intensity is related to the P(DCS); it may be related to the
      intensity of the stimulus to a power (alpha). Our stimuli are defined as pressure
      ratio [PR = (phi P1N2/ P2)-11] or pressure difference [delta P = phi P1N2-P2],
      where phi P1N2 is the N2 partial pressure calculated in the 360 min half-time
      (t1/2) compartment or t1/2 is estimated with other parameters and P2 is ambient
      pressure after the ascent. Both stimuli represent a potential released volume of
      gas. We tested the null hypothesis that alpha > 1 was no better than alpha = 1 in
      PR alpha and delta P alpha in a log logistic survival analysis of 1085 exposures
      in hypobaric chambers. The log likelihood number increased from -1198 for alpha =
      0 for the null model to -724 for PR alpha when alpha = 3.52 with a 42 min t1/2
      and -714 for delta P alpha when alpha = 8.44 with a 91 min t1/2. We conclude that
      the improvement in our expressions for decompression dose with alpha > 1 is not
      by random chance and that alpha may link the physics of gas evolution to the
      biology of pain perception. Because of our empirical approach, we do not exclude
      other possible interpretations.

PMID- 9561283
TI  - A comparison of heart rate, eye activity, EEG and subjective measures of pilot
      mental workload during flight.
AB  - BACKGROUND: Mental workload is a major consideration in the design and operation
      of modern aircraft systems. Objective measures of mental workload that are
      sensitive and diagnostic are required to meet the needs of both pilots and
      designers. Due to the multifaceted nature of these complex mental demands
      multiple measures are required. HYPOTHESIS: Psychophysiological and subjective
      measures provide unique information about mental workload during flight. METHODS:
      Cardiac, eye, brain and subjective data were collected during an actual flight
      scenario designed to provide tasks which required different piloting skills at
      several levels of mental workload. RESULTS: Heart rate was sensitive to the
      demands of flight but not diagnostic with regard to determining the cause of the
      workload. Heart rates increased during take offs and landings and to an
      intermediate level during instrument flight rules (IFR) segments. By showing
      sensitivity to only the visual demands of the various segments of flight eye
      activity was more diagnostic. The theta band of the EEG demonstrated increased
      power during those flight segments which required inflight mental calculations.
      The subjective measures showed trends suggesting different levels of mental
      demand but demonstrated few statistically significant differences. CONCLUSIONS:
      Multiple measures, especially psychophysiological measures, provide a
      comprehensive picture of the mental demands of flight. The measures used in this
      study were shown to provide unique, non-overlapping information. Because of the
      continuous nature of the psychophysiological data it may be possible to develop
      systems which provide on-line monitoring of mental workload that can provide
      feedback to the pilot and aircraft systems.

PMID- 9561284
TI  - The effects of low levels of CO2 on ventilation during rest and exercise.
AB  - BACKGROUND: Measurements of pulmonary gas exchange are especially sensitive to
      low levels of CO2 in the environment; this is an important consideration in
      measurements in enclosed spaces. METHODS: In order to determine the responses to
      these low levels, subjects were exposed in five studies to partial pressures of
      inspired CO2 (PICO2) of 5.7 and 7.5 mmHg for 30 min during basal conditions at
      rest and to 5.4, 9.4 and 15 mmHg during a progressive exercise to VO2max on a
      cycle ergometer. RESULTS: In the two resting studies, total pulmonary ventilation
      and alveolar ventilation were increased by 19% at 7.5 mmHg (1.1% sea level
      equivalent) and 10% at 5.4 mmHg (0.8% equivalent), with clear evidence of CO2
      retention in both studies. During exercise at 15 mmHg the VO2max was reduced
      significantly by 13%, compared with air at about the same maximal ventilation,
      but VO2max was not reduced at 9.4 mmHg. A 6% decrease in VO2max at a PICO2 of 5.4
      mmHg may have resulted from these subjects being less fit. The maximal CO2 output
      and respiratory exchange ratio in the three exercise studies was always lower
      with CO2 than corresponding air measurements, indicating CO2 storage. Evaluation
      of submaximal measurements provided an equation for predicting ventilation as a
      function of PICO2 and VO2/VO2max and demonstrated that ventilation during
      submaximal exercise is increased significantly by the lowest CO2 level. BP and
      heart rate responses during submaximal and maximal work were not predictably
      altered by CO2 at these levels. CONCLUSION: These studies demonstrate that
      minimal CO2 levels have significant influences on pulmonary ventilation during
      rest and exercise and must be considered in acute studies in confined spaces such
      as space cabins. The inspired CO2 should be stated when ventilation measurements
      are reported under these conditions.

PMID- 9561285
TI  - Hypervolemia in men from fluid ingestion at rest and during exercise.
AB  - BACKGROUND: Plasma osmolality (Osm) is important for controlling and maintaining
      plasma volume (PV) and body water. The effect of oral rehydration fluids for
      ameliorating dehydration is well-established; but optimal composition and Osm of
      fluids for hyperhydrating normally hydrated subjects is less clear. METHODS: Six
      treatments were used without and with oral fluids of varying ionic and
      constituent concentrations for hyperhydrating six previously euhydrated men (30
      +/- SD 8 yr, 76.84 +/- 16.19 kg, 73 +/- 12 ml.kg-1 PV, 40 +/- 10 ml.min-1.kg-1
      peak VO2) sitting at rest for 90 min (VO2 = 0.39 +/- SE 0.02 L.min-1) and during
      subsequent 70 min of submaximal exercise (VO2 = 2.08 +/- SE 0.33 L.min-1, 70 +/-
      7% peak VO2). The hypothesis was that the fluid composition is more important
      than plasma Osm for increasing PV in euhydrated subjects at rest and maintaining
      it during exercise. Drink formulation compositions, given at 10 ml.kg-1 body wt,
      (mean = 768 ml), for the sitting period were: Performance 1 (P1; 55 mEq Na+, 365
      mOsm.kg H2O-1), P2 (97 mEq Na+, 791 mOsm.kg-1), P2G (113 mEq Na+, 4% glycerol,
      1382 mOsm.kg-1), AstroAde (AA; 164 mEq Na+, 253 mOsm.kg-1), and 01 and 02 (no
      drinking). The exercise drink (10 ml.kg-1, 768 ml) was P1 for all treatments
      except 02 (no drinking); thus, drink designations were: P1/P1, P2/P1, P2G/P1,
      AA/P1, 0/P1, and 0/0. RESULTS: PV at rest increased (p < 0.05) by 4.7% with P1
      and by 7.9% with AA. Percent change in PV during exercise was +1% to +3% (NS)
      with AA/P1; -6% to 0% (NS) with P1/P1, P2/P1, P2G/P1, and 0/P1; and -8% to -5% (p
      < 0.05) with 0/0. AA, with the lowest Osm of 253 mOsm.kg-1, increased PV at rest
      (as did P1) and maintained it during exercise, whereas the other drinks with
      lower Na+ and higher Osm of 365-1382 mOsm.kg-1 did not. CONCLUSION: Drink
      composition appears to be more important than its Osm for increasing PV at rest
      and for maintaining it during exercise in previously euhydrated subjects.

PMID- 9561286
TI  - Low level CO2 effects on pulmonary function in humans.
AB  - The purpose of the study was to determine whether chamber exposure to low levels
      of CO2 results in functional alterations in gas mixing and closing volume in
      humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2.
      Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for
      carbon monoxide (DLCO) by two methods, and cardiac output were measured in
      triplicate. Values were obtained over two non-consecutive days during the
      training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to
      each CO2 level. Measurements were made during the same time of day. There was one
      day of testing after exposure, while still in the chamber but off carbon dioxide.
      The order of testing, up until measurements of DLCO and cardiac output, were
      randomized to avoid presentation effects. The consistent findings were a
      reduction in diffusing capacity for carbon monoxide and a fall in cardiac output,
      occurring to a similar degree with both exposures. For the group as a whole,
      there was no indication of major effects on spirometry, lung volumes, gas mixing
      or dead space. We conclude that small changes may occur in the function of distal
      gas exchanging units; however, these effects were not associated with any adverse
      health effects. The likelihood of pathophysiologic changes in lung function or
      structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore,
      low.

PMID- 9561287
TI  - Hypercapnic ventilatory response in humans before, during, and after 23 days of
      low level CO2 exposure.
AB  - Alterations in ventilation and the chemoreceptor response to CO2 during 23 d of
      1.2% inspired CO2 were studied in four male subjects. Resting ventilation (VE),
      tidal volume (VT), respiratory frequency (fR), inspired and end tidal O2 and CO2
      and the hypercapnic ventilatory response (HCVR) measured by CO2 rebreathing were
      measured once before entering the chamber, on days 2, 5, 11, and 22 of CO2
      exposure, and one day after. Resting VE slightly increased (5%) on day 2 of
      exposure and significantly increased (22%) by day 5 followed by a progressive
      decrease to pre-chamber levels by day 22 and on the first day of recovery. Tidal
      volume and fR were not statistically different. During the exposure PetCO2 was
      significantly elevated with day 2 having the largest increase (19.6%). PetCO2
      returned to normal within 24 h post exposure. The HCVR was characterized by the
      slope (SHCVR), intercept at zero ventilation (B), and the ventilation at a PCO2 =
      60 mmHg (VE60). The SHCVR decreased (14%) on day 2, but was not significant; the
      SHCVR on the other exposure days were also not different. The SHCVR on the first
      recovery day significantly increased (37%). The HCVR B was shifted to the right
      on day 2 by 5.2 mmHg, then progressively returned to the pre-exposure position.
      On recovery the B significantly shifted 6.9 mmHg to the right of pre-exposure B.
      The VE60 decreased by approximately 32% and 16% on day 2 and 5, respectively,
      then returned within pre-exposure range for the remainder of the exposure and
      during recovery. During the early phase and one day after the exposure the HCVR
      was right shifted. One day after exposure chemoreceptor sensitivity to elevated
      CO2 was increased but, the B was right shifted resulting in a reduced HCVR below
      PCO2 of 60 mmHg and a greater HCVR above 60 mmHg.

PMID- 9561288
TI  - Effects of chronically increased ambient CO2 concentrations on aerobic capacity.
AB  - As part of a joint NASA-ESA-DARA study on the effects of chronically increased
      CO2 concentrations in ambient air, changes in parameters indicating aerobic
      capacity were investigated by cycle ergometry. Two potential sources for
      reductions of aerobic capacities were hypothesized: 1) the adaptations to CO2
      such as reduction in H(+)-buffer capacities which may influence muscle
      metabolism; 2) the reduced physical activities which may lead to a detraining
      effect. Four subjects were exposed to 0.7% and 1.2% CO2 concentration in a
      confined compartment for 23 d each with 3 mo in between the two campaigns. A
      combined exercise test was applied before, during (on days 5, 11, and 22) and
      after CO2 exposure. Comparing steady-states at 30 W and 80 W power, elevated
      ventilation was found increased during CO2 exposure with significant differences
      between the two campaigns. Peak oxygen uptake decreased over the period of CO2
      exposure, but was found not significantly different on day 5 compared to pre
      exposure measurements. This decrease was not dependent on the CO2 concentration.
      The lactate concentration at low exercise intensities was found elevated during
      CO2 exposure. A shift in reverse direction was observed after the CO2 exposure.
      Since peak oxygen uptake did not differ on day 5 and the lactate concentration
      was found increased, it was concluded that the potential changes in muscle
      metabolism by adaptation to elevated CO2 concentrations did not influence the
      aerobic capacities. Therefore, it was concluded that the changes in aerobic
      capacities are the result of the reduced physical activities of the subjects
      while living in the confined compartment.

PMID- 9561289
TI  - Towards new paradigms for the treatment of hypobaric decompression sickness.
AB  - Altitude induced (hypobaric) decompression sickness (DCS) has long been treated
      with ground level oxygen and U.S. Navy Treatment Tables 5 and 6. These treatment
      tables originate from surface excursion diving and, when implemented, require
      significant resource allocation. Although they are effective treatment regimens,
      these tables were not developed for treating hypobaric DCS which has an etiology
      similar to saturation diving DCS. In this review, different treatment options for
      hypobaric DCS are presented. These options include more aggressive use of ground
      level oxygen and treatment tables using a maximum pressure of 2 atmospheres
      (ATA). Specific attention is given to USAF Table VIII, an experimental hypobaric
      DCS treatment-table, and space suit overpressurization treatment. This paradigm
      shift for DCS treatment is based on a projected increase in hypobaric DCS
      treatment from exposure to low pressure during several operational conditions:
      cruise flight in the next generation aircraft (e.g., F-22); high altitude,
      unpressurized flight by special operations forces; and the extraordinary amount
      of extravehicular activity (EVA) required to construct the international space
      station. Anticipating the need to treat DCS encountered during these and other
      activities, it is proposed that 2 ATA or less hyperbaric oxygen (HBO) treatment
      conjoined with new collapsible chamber technology can be used to address these
      issues in a safe and cost effective fashion.

PMID- 9561290
TI  - An objective measure of seat comfort.
AB  - Uncomfortable aircrew seating is more than just a nuisance, it has the potential
      to produce a cumulative trauma which can significantly affect attention,
      information processing, and task performance to the extent of interfering with
      mission completion or contributing to mishaps. Yet, for decades uncomfortable
      seating has endured as an aircrew complaint with little progress made toward
      resolving it. Aircraft design techniques have steadily progressed, but the method
      for ascertaining seating pressure issues has remained, unfortunately, the same:
      simply ask aircrew where it hurts and hope some cushion changes work. Currently,
      there exist sensor technologies which potentially can economically and
      effectively address this problem by reducing the comfort analysis to the
      examination of an objective, quantitative pressure map. This technical note
      discusses the brief history of seat pressure measurement research, enumerates
      some of the technologies that are available that can be applied to the problem,
      and finally, describes a seated pressure measurement demonstration which shows
      the power of the approach for maximizing comfort.

PMID- 9561291
TI  - The 17th Andre Allard Memorial Lecture: to smoke or not to smoke in civil
      aviation.

PMID- 9561292
TI  - Protocol for the evaluation of coronary artery disease.

PMID- 9561293
TI  - Defence evaluation and research agency centre for human sciences.

PMID- 9561294
TI  - Report of the inflight emergency medical kit task force. Emergency Medical Kit Ad
      Hoc Task Force. Aerospace Medical Association.

PMID- 9561295
TI  - Mitochondria revisited. Alternative functions of mitochondria.
AB  - This review explores the alternative functions of mitochondria inside the cell.
      In a general picture of mitochondrial functioning, the importance and uniqueness
      of these intrinsic functions make them irreplaceable by other intracellular
      compartments. Among these are, participation in apoptosis and cellular
      proliferation, regulation of the cellular redox state and level of second
      messengers, heme and steroid syntheses, production and transmission of a
      transmembrane potential, detoxication and heat production. In most of the listed
      functions, reactive oxygen species modulate a number of non-destructive cellular
      activities. Some of the mitochondrial functions are reviewed in detail.

PMID- 9561296
TI  - An uncoupling of the processes of oxidation and phosphorylation in glycolysis.
AB  - Data on alterations of the properties of glyceraldehyde-3-phosphate dehydrogenase
      upon oxidation of its functional groups are reviewed; a mechanism of uncoupling
      of oxidation and phosphorylation in glycolysis is considered. Possible ways of
      regulating uncoupling, and the physiological importance of this process, are
      discussed.

PMID- 9561297
TI  - Mitochondrial dehydrogenases in different taxa of tetrahymena: effect of insulin.
AB  - Mitochondrial dehydrogenase activity was measured in seven taxa of Tetrahymena
      (T. pyriformis G1. T. hegewishi, T. malaccensis, T. pigmentosa, T. shapiro, T.
      thermophila CU-399, T. thermophila MS-1). Enzyme activity was different in the
      taxa investigated. Insulin reduced enzyme activity in six of the seven taxa
      studied. The duration of activity reduction was relatively long (5-10 min.) in
      most of the cases, and in T. hegewishi this lasted up to the end of the
      measurements (30 min.). There was no interrelation between the basic
      dehydrogenase activity of the taxon and the effect of insulin. There was also no
      correlation between the degree of relationship (of the taxa) and the
      dehydrogenase profile after insulin treatment.

PMID- 9561298
TI  - Imprinting effects of proline containing dipeptides (proline-glycine, proline
      leucine, proline-valine and their retro variants) in tetrahymena. Evolutionary
      conclusions.
AB  - Proline-glycine, proline-leucine and proline-valine dipeptides and their retro
      variants were used in the experiments to study the effects of pretreatment
      (imprinting) in Tetrahymena, by investigating fluorescein isothiocyanate (FITC)
      conjugated peptide binding. The protozoan organism could differentiate between
      the proline-dipeptides containing different partner amino-acids and between the
      dipeptides having the amino acids in reversed positions. The effect of imprinting
      was positive or negative and this was dependent on the type of the partner amino
      acid and on its position. Pro-Gly and Pro-Leu induced positive imprinting
      (elevated FITC-dipeptide binding) and Pro-Val induced negative imprinting
      (decrease of FITC-peptide binding). There was positive imprinting induction in
      two cases for the retro FITC-peptide and in one case for the FITC-conjugate of
      the imprinter peptide itself. The highest positive imprinting (almost 60%
      increase) was induced by Pro-Gly for FITC-Gly-Pro. Considering earlier-
      chemotaxis--experiments, the results of the present--binding--studies run
      parallel with the physiological effects. The experiments call attention to the
      sharp differentiating ability of small peptides at a unicellular level, that
      could have some role in the selection of molecules for hormone formation, during
      evolution.

PMID- 9561299
TI  - Sodium nitrite alone protects the brain microsomal Ca(2+)-ATPase against
      potassium cyanide-induced neurotoxicity in rats.
AB  - The effect of a short-term oral administration of potassium cyanide (KCN) (200
      ppm in diet) with or without sodium nitrite (NaNO2) pretreatment on rat brain
      microsomal Ca2 +/- ATPase was investigated. The specific activity value of the
      enzyme significantly decreased (p < 0.05) by 50% compared with control and by 63%
      for KCN-treated rats compared with KCN-treated rats pretreated with NaNO2. There
      was no significant difference at the h = 0.05 level between the values obtained
      for the control and KCN-treated rats pretreated with NaNO2. These results show
      both that feeding lowers brain microsomal Ca(2+)-ATPase activity and that NaNO2
      has a protective role (antidote function) in that respect.

PMID- 9561300
TI  - Apoptosis dependent decrease of the intramembrane ion traffic in cultured mouse
      fibroblasts shown by conductivity dispersion.
AB  - We have investigated the intramembranal ion traffic in apoptotic 3T6 cells in
      culture. Apoptosis was induced by various treatments, such as serum deprivation,
      high density growth and hydrogen peroxide at subnecrotic doses. Cell death was
      assessed by nucleosomal DNA fragmentation, single cell electrophoresis,
      immunofluorescence and histological staining. To study the modifications of
      membrane structure and function, we adopted a well established biophysical
      strategy based on the measurement of the electrical conductivity of cell
      suspensions, as a function of the frequency of the electrical field applied to
      the sample. A comparison between the conductivity of normal and apoptotic cell
      suspensions shows that programmed cell death causes a decrease of membrane
      conductivity which indicates a diminished intramembranal ion traffic. Our results
      strongly suggest that one of the early events in the triggering of apoptosis is
      represented by an overall reduction of plasma membrane function. Finally, our
      results are in agreement with the idea that the nucleus is not the sole target of
      the apoptotic process.

PMID- 9561301
TI  - Sensitivity of Ca2+ transport of mitochondria to reactive oxygen species.
AB  - The relationship between Ca2+ transport and energy transduction of myocardial
      mitochondria in the presence of reactive oxygen species was investigated.
      Following treatment with oxygen free radicals [superoxide(O2.-) or hydroxyl
      radical (.OH)], lipid free radicals in myocardial mitochondrial membrane could be
      detected by using the method of EPR spin trap. Simultaneously there were obvious
      alterations in the free Ca2+ ([Ca2+]m) in the mitochondrial matrix; the physical
      state of membrane lipid; the efficiency of oxidative phosphorylation (ADP/O); the
      value of the respiratory control ratio (RCR); and the membrane potential of the
      inner membrane of myocardial mitochondria. If the concentrations of reactive
      oxygen species were reduced by about 30%, the alterations in the physical state
      of the membrane lipid and energy transduction of myocardial mitochondria were not
      observed, but the changes in Ca2+ homeostasis remained. We conclude that Ca2+
      transport by myocardial mitochondria is more sensitive to agents such as O2.- or
      OH, etc. than are oxidation phosphorylation and the respiratory chain.

PMID- 9561302
TI  - Psychoanalytic psychotherapy with men with intellectual disabilities: a
      preliminary outcome study.
AB  - Psychotherapy has been demonstrated to be an effective form of treatment for
      people with psychological problems. However, there is considerable resistance to
      attempts to generalize these findings to people with intellectual disabilities.
      Such therapeutic disdain has a long history without any empirical foundation.
      Recently it has been argued on philosophical grounds that people with
      intellectual disabilities should have access to the same services as everyone
      else. Furthermore, that people with intellectual disabilities should be actively
      targeted as they are more likely to have psychological difficulties than non
      handicapped people. The therapeutic literature concerning people with
      intellectual disabilities is overwhelmingly behavioural. More recently various
      psychotherapeutic approaches have been explored as alternatives to behavioural
      interventions. Publication of several case studies in the late 1980s and early
      1990s has provided some evidence for the benefit of various psychotherapeutic
      approaches with people with intellectual disabilities. However, there are no
      outcome studies. This paper reports an outcome study of individual psychoanalytic
      psychotherapy provided in normal clinical practice for 25 men with intellectual
      disabilities who were referred for behaviour problems. Of the 25 participants in
      the study, 20 completed treatment. In most cases the problem behaviour was
      eliminated and this was maintained at six months follow-up.

PMID- 9561303
TI  - The role of personal therapy for therapists: a review.
AB  - This paper reviews the research literature on personal therapy and makes some
      recommendations for how future work in this area may be improved. Despite the
      general acceptance of the importance of personal therapy amongst therapists,
      there has been relatively little research to evaluate its effectiveness. The vast
      majority of studies have consisted of surveys of therapists' opinions and
      experiences of therapy or naturalistic comparisons across therapists who have or
      have not had therapy. The interpretation of most findings is compromised because
      of small sample sizes and confounding variables, nevertheless some conclusions
      can be made. Whilst the majority of therapists feel that they have benefited
      professionally from personal therapy there is very little empirical evidence that
      it has any measurable effect on client outcome. However, there is some evidence
      that personal therapy has a positive effect on those therapist qualities often
      cited as constructive to client change (e.g. empathy, warmth, genuineness). What
      is evident is that there is a need for more methodologically sound research as
      well as a more theoretical understanding of how personal therapy affects clinical
      practice, before any firm conclusions can be drawn about its usefulness. It is
      suggested that it may be more useful for future research in this area to focus on
      therapy process rather than client outcome.

PMID- 9561304
TI  - A current psychodynamic understanding of panic disorder.
AB  - While there has been burgeoning interest in the psychiatric literature about the
      phenomenology and biology of panic disorder, there is little new information
      about the psychodynamics of this condition. The reintroduction of a psychodynamic
      perspective could be useful in guiding research strategies to identify traits
      which predispose to panic and in designing treatments to address such traits. A
      psychodynamic model hypothesizes a relationship between current psychological
      functioning, early experiences, and ongoing psychological traits. Recent
      published reports about the nature of underlying psychodynamics and psychological
      characteristics of panic disorder are discussed.

PMID- 9561305
TI  - Asthma and menstruation: the relationship between psychological and bronchial
      hyperreactivity.
AB  - The aim of this study was to investigate a possible interrelation between
      bronchial hyperreactivity and psychological hyperreactivity. In order to record
      changes in both bronchial and psychological reactions throughout the menstrual
      cycle, 10 women out-patients with moderate asthma were followed up for six
      months, and their physical and psychological status as well as their reactions to
      life-events and environmental influences were assessed through self-reporting
      measures and weekly psychotherapeutic sessions. Psychotherapy was used both as a
      supplement to the medical treatment and as a method of data collection. A
      relationship between lowered resistance to stress, lowered resistance to
      infections and increased bronchial hyperreactivity is suggested as background
      aetiological factors for the exacerbation of asthma around menstruation.

PMID- 9561306
TI  - Attachment representations and representations of the self in relation to others:
      a study of preschool children in inner-city London.
AB  - The study examined the relationship between attachment representations and
      representations of the self in relation to others in a sample of 42 children aged
      between 4 and 5.9 years. The relationship between children's attachment
      representations and parents' style of regulating negative affect was also
      explored. The families were using local authority day-care facilities in a
      deprived inner-city area of London. The quality of attachment representations was
      assessed using a modified version of the Separation Anxiety Test. Assessments of
      the representation of the self in relation to others consisted of (a) assessment
      of the child's view of self within the relationship with the attachment figure,
      using an incomplete doll story procedure; and (b) assessment of the child's
      perceptions of the way others view them using a puppet interview. Significant
      connections between attachment representations, representations of self in
      relation to others, and parents' negative affect regulation were found. Children
      with secure attachment representations had a significantly more positive view of
      the self in the relationship with the attachment figure than children with
      disorganized attachment representations, and a significantly more positive
      perception of the way others view them than children with avoidant attachment
      representations. Children with secure attachment representations had parents with
      more adaptive ways of regulating their own negative affect than children with
      ambivalent or disorganized attachment representations.

PMID- 9561307
TI  - A group for the adult daughters of mentally ill mothers: looking backwards and
      forwards.
AB  - A closed time-limited therapy group was conducted for four women who had all been
      raised by mentally ill mothers. Themes recurring frequently included hatred of
      self and mother, current lack of extended family support, current parenting
      difficulties, ongoing stigma and isolation. All group members perceived
      themselves as troubled despite others' perceptions of them as resilient. The
      results for the individuals treated are outlined using clinical material, as
      statistical analysis was not undertaken. All were able to cease individual
      therapy. Conclusions focus on the benefits of such a group process of recognition
      and affirmation of the profound consequences of a mother's mental illness on her
      daughters and thence to grandchildren. The possibility of primary prevention
      using techniques from infant-parent and child-group therapy is discussed.

PMID- 9561308
TI  - The contribution of depression and denial towards understanding the unawareness
      of symptoms in schizophrenic out-patients.
AB  - OBJECTIVES: Unawareness of schizophrenic symptoms was postulated to be partially
      attributable to patients denying symptoms in order to avoid depression. METHOD:
      The 24-item version of the Brief Psychiatric Rating Scale (BPRS) was administered
      to 41 schizophrenic patients (chart diagnoses were validated by a DSM-III-R
      checklist). The first 14 of these items were then used to gather information
      about patients' symptomatology from 55 relatives of patients. Unawareness of
      symptoms was calculated by subtracting patients' total for these 14 items from
      parents' totals. Two measures of depression were obtained. Subjective depression
      was the score on the depression item based on patients responses to interview
      questions, objective depression was the score based on interviews with relatives
      about their ill family member. Family functioning was also assessed by
      administering patients' relatives the Camberwell Family Interview and the FACES
      III. RESULTS: Hierarchical regression analyses revealed that both subjective and
      objective measures of depression were significantly related to unawareness;
      subjective depression was negatively related, and objective depression was
      positively related. The employed measures of family functioning were unrelated to
      unawareness of symptomatology. CONCLUSION: This opposing pattern of subjective
      and objective depression was interpreted as evidence of the self-deception which
      characterizes all defence mechanisms including denial.

PMID- 9561309
TI  - Psychological functioning in primary progressive versus secondary progressive
      multiple sclerosis.
AB  - Psychological functioning in two types of multiple sclerosis (MS) patients is
      assessed: primary progressive (PP) and secondary progressive (SP) patients. On
      the basis of differences in clinical course and underlying pathology we
      hypothesized that primary progressive patients and secondary progressive patients
      might have different psychological functioning. Seventy patients treated in an MS
      centre were examined cross-sectionally. Forty had an SP course of MS and 30 a PP
      course. The 33 male and 37 female patients had a mean age of 48.4 years (SD 11.2)
      and mean age of onset of MS of 30.7 years (SD 11.1). Patients completed
      questionnaires measuring among others the following aspects of psychological
      functioning: depression (BDI, SCL-90), anxiety (STAI, SCL-90), agoraphobia (SCL
      90), somatic complaints (SCL-90), hostility (SCL-90) and attitude towards
      handicap (GHAS). Patients with a PP-MS scored significantly better on 5 out of 14
      subscales than patients with SP-MS (p < .05). On the basis of our
      operationalizations of psychological functioning, the findings support the
      conclusion that on average 18 years after diagnosis of MS, amongst patients
      attending an MS unit, primary progressive patients were found to have better
      psychological functioning.

PMID- 9561310
TI  - On facing facts: what kinds of information do pre-assessment psychotherapy
      questionnaires provide?
AB  - More than two-thirds of NHS psychotherapy departments now use questionnaires in
      assessment of new patients. Their content is described for the first time. Most
      are primarily designed to gather biographical information but salient questions
      are frequently omitted. These questionnaires have suffered from being designed
      and used in isolation. Psychotherapy service providers need to consider how
      collaboration will enable questionnaires to be more effective during their
      assessments and to assist research into which historical factors are of greatest
      prognostic significance among newly referred patients.

PMID- 9561311
TI  - Managing patients with personality disorders.

PMID- 9561312
TI  - Treatment outcome of personality disorders.
AB  - OBJECTIVE: To review the treatment outcome of personality disorders. METHOD: A
      literature search of studies pertaining to personality disorder and outcome was
      conducted, and studies that focused primarily on Axis II were retained. Of these,
      naturalistic outcome studies were distinguished from those that addressed
      treatment outcome specifically. The treatment outcome studies were examined in
      terms of type of treatment intervention, dependent variables, and outcome.
      RESULTS: Contrary to contemporary assumptions about Axis II, a substantial number
      of treatment outcome studies were identified. Trends in the assumptions
      underlying psychosocial and pharmacologic approaches were identified on the basis
      of dependent variables. CONCLUSION: There is evidence that effective treatments
      exist to alleviate symptoms and reduce symptomatic behaviours that accompany
      personality disorders. What these results hold for the idea of remission from
      personality disorder is considered.

PMID- 9561313
TI  - Developing effective services for patients with personality disorders.
AB  - OBJECTIVE: This review focused on empirical research that addressed the
      effectiveness of service models for the care of patients with personality
      disorders. METHOD: Services discussed included those delivering acute care, such
      as crisis and emergency services and acute psychiatric hospitalization;
      continuing care, such as outpatient services, day hospital treatment, and
      assertive community treatment programs; and other community programming, such as
      integrated treatment for comorbid substance abuse and psychoeducational
      interventions for families of patients with personality disorders. The review
      focused on studies that included patients with personality disorders, and it
      measured outcomes relevant to patients with personality disorders. Evidence from
      randomized controlled trials was highlighted. RESULTS: Few systematic studies of
      acute services were available. Community programming can decrease the risk of
      suicide attempts and reliance on inpatient admissions. Services must develop
      methods of ensuring compliance with treatment. Assertive community treatment for
      Axis II patients should be developed, implemented, and tested. Comprehensive
      programming for patients with personality disorders must include integrated
      treatment for substance abuse and family psychoeducational programs. CONCLUSION:
      Promising new models of care for patients with personality disorders are ready
      for testing and wider application.

PMID- 9561314
TI  - The first asylums in Canada: a response to neglectful community care and current
      trends.
AB  - OBJECTIVE: Humane treatment and care of mentally ill people can be viewed from a
      historical perspective. Intramural (the institution) and extramural (the
      community) initiatives are not mutually exclusive. METHOD: The evolution of the
      psychiatric institution in Canada as the primary method of care is presented from
      an historical perspective. A province-by-province review of provisions for
      mentally ill people prior to asylum construction reveals that humanitarian
      motives and a growing sensitivity to social and medical problems gave rise to
      institutional psychiatry. The influence of Great Britain, France, and, to a
      lesser extent, the United States in the construction of asylums in Canada is
      highlighted. The contemporary redirection of the Canadian mental health system
      toward "dehospitalization" is discussed and delineated. RESULTS: Early promoters
      of asylums were genuinely concerned with alleviating human suffering, which led
      to the separation of mental health services from the community and from those
      proffered to the criminal and indigent populations. While the results of the past
      institutional era were mixed, it is hoped that the "care" cycle will not repeat
      itself in the form of undesirable community alternatives. CONCLUSION: Severely
      psychiatrically disabled individuals can be cared for in the community if
      appropriate services exist.

PMID- 9561315
TI  - Prospective follow-up study of borderline personality disorder: prognosis,
      prediction of outcome, and Axis II comorbidity.
AB  - OBJECTIVE: To examine the rate of persistence of borderline personality disorder
      (BPD), the existence of concomitant personality disorders on follow-up, and the
      predictors of outcome in patients who met criteria for BPD compared with patients
      with borderline features who failed to meet all of the criteria. METHOD: This
      prospective cohort study reassessed subjects for BPD diagnosis and cooccurring
      personality pathology at 7 years follow-up. Initial measures of borderline and
      comorbid personality psychopathology were used to predict levels of borderline or
      other personality disorder psychopathology at follow-up. RESULTS: Of the 57
      subjects who initially met the criteria for BPD, 30 (52.6%) were found to have
      remitted BPD, and 27 (47.4%) were characterized as having persistent BPD. The
      remitted group met significantly fewer comorbid personality disorder diagnoses
      than the persistent group (mean = 0.8, mean = 3.5 respectively; P < 0.05).
      Results also indicated that the initial level of borderline psychopathology was
      predictive of borderline psychopathology at follow-up, which explained 17% of the
      variance. CONCLUSIONS: This prospective follow-up study found that almost 50% of
      former inpatients with BPD continue to test positive for BPD at 7 years follow
      up, and these persistent BPD patients also had significantly more comorbid
      personality psychopathology. Borderline psychopathology at follow-up was
      primarily predicted by the level of borderline psychopathology recorded at the
      initial assessment.

PMID- 9561316
TI  - Impairment of semantic categorization processes among thought-disordered
      schizophrenic patients.
AB  - OBJECTIVE: To explore semantic categorization strategies in patients with
      schizophrenia. METHOD: A short-term memory-recognition task that reveals the
      effects associated with categorization was created and applied to 2 groups of
      patients with schizophrenia and depression. RESULTS: Only the schizophrenic
      subgroup with formal thought disorder (measured using Andreasen's Thought,
      Language, and Communication [TLC] scale) exhibited a deficiency in semantic
      categorization strategies during the task. CONCLUSION: These results support the
      hypothesis of the impairment of the processes involved in the processing of
      contextual information in patients with schizophrenia who suffer from formal
      thought disorder.

PMID- 9561317
TI  - Neuroendocrine responses to inhibitors of steroid biosynthesis in patients with
      major depression resistant to antidepressant therapy.
AB  - OBJECTIVE: Patients with major depression frequently have high cortisol levels
      and resistance to dexamethasone. We sought to determine to what extent major
      depression might be influenced by inhibitors of steroid biosynthesis and to study
      the endocrine changes produced. METHOD: After drug washout, 20 treatment
      resistant patients with major depression were given aminoglutethimide,
      metyrapone, and/or ketoconazole, along with a small dose of cortisol for 8 weeks.
      Hamilton Depression Rating Scale (HDRS) ratings, 8:00 AM cortisol
      dehydroepiandrosterone sulfate (DHAS), adrenocorticotropin (ACTH), and
      testosterone levels were followed weekly or oftener. A dexamethasone suppression
      test (DST) was conducted before and after treatment. RESULTS: Seventeen patients
      (85%) completed the course of treatment, and a significant mean drop (P < or =
      0.0001) of 50% in the HDRS score occurred by 7 weeks of treatment. Cortisol
      levels fluctuated widely and were often still high after the patient had improved
      clinically. Dehydroepiandrosterone sulfate levels fell more uniformly and were
      found to be a useful indicator of compliance and, to some extent, efficacy with
      aminoglutethimide and ketoconazole therapy. The correlation between DHAS and HDRS
      (r = 0.94) was significant (P = 0.02). Testosterone levels in men fell with
      ketoconazole but returned promptly to normal at the end of treatment.
      Adrenocorticotropin levels were normal or elevated, depending on the assay used,
      and rose (P = 0.07; n = 13) in most subject during therapy. Of the 6 responders
      who had nonsuppressor DSTs before starting therapy, 5 had reverted to normal 1 to
      2 weeks following cessation of therapy (P = 0.0006). CONCLUSIONS: Abnormal
      metabolism of adrenocortical steroids may perpetuate depression, and alterations
      of synthesis or metabolism of these steroids may lead to a remission.

PMID- 9561318
TI  - Fitness to stand trial: characteristics of remands since the 1992 Criminal Code
      amendments.
AB  - OBJECTIVE: To examine the characteristics of a sample of remands after the
      introduction of the 1992 Criminal Code amendments, to compare those deemed fit
      with those deemed unfit as the result of an institution-based evaluation of
      fitness, and to determine the impact of the Code changes on one's detention
      period by investigating the length of time that individuals were held on remand.
      METHOD: File information was collected and analyzed for 180 males who were
      remanded for inpatient evaluations of their fitness to stand trial between
      October 1994 and July 1995. RESULTS: The results indicated that remanded
      defendants are more likely to be single, unemployed, and living alone and that
      unfit defendants are significantly more likely to have never been married. As
      well, individuals who were found to be unfit to stand trial were significantly
      less likely to have been diagnosed with a drug- or alcohol-use disorder and were
      4 times more likely to have been diagnosed with a psychotic disorder. The results
      also indicated that while the 1992 Criminal Code revisions called for a 5-day
      evaluation period, it appears that this is rarely accomplished, and, in fact, the
      average length of time for an assessment of fitness is 23 days. Finally, the
      majority of remanded individuals are certified and treated with psychotropic
      medications while on remand. CONCLUSION: The results of this study suggest that
      the fitness remand period is being used for purposes other than assessing
      fitness.

PMID- 9561319
TI  - Anxious attachment and self-reported depressive symptomatology in women.
AB  - OBJECTIVE: Lack of intimacy has been identified as an important provoking agent
      that increases the risk of depressive symptoms in women. This study precisely
      characterized lack of intimacy by assessing a woman's attachment style and
      investigated the specificity of association between depressive symptoms and an
      anxious attachment pattern. METHOD: Four hundred and twenty women participated in
      this cross-sectional study of depressive symptomatology and anxious attachment.
      All participants completed the following measures: a sociodemographic
      questionnaire, the Centre for Epidemiological Studies Depression Scale (CES-D),
      the Reciprocal Attachment Questionnaire, the Social Support Questionnaire, the
      Rosenberg Self-Esteem Scale, and the Global Assessment of Recent Stress Scale.
      RESULTS: A score of 16 or above on the CES-D, which indicates the presence of
      depressive symptoms, was used to divide the sample into 2 groups: a depressed
      group (N = 129) and a nondepressed group (N = 291). We found that women in the
      depressive symptomatology group were more likely than women in the nondepressive
      symptomatology group to exhibit anxious attachment and adverse social and
      cognitive characteristics. Lower levels of self-esteem and higher levels of
      recent stress were also predictive of depressive symptomatology. Feared loss of
      the attachment figure and a lack of use of the attachment figure were independent
      predictors of depressive symptomatology in the same model. CONCLUSION: The feared
      loss of security associated with an attachment figure seems to be related to an
      increased likelihood of depressive symptoms.

PMID- 9561320
TI  - Gabapentin: long-term antianxiety and hypnotic effects in psychiatric patients
      with comorbid anxiety-related disorders.

PMID- 9561321
TI  - ECT continuation and maintenance in a patient with psychosis and mental
      disability.

PMID- 9561322
TI  - All that seizes is not clozapine.

PMID- 9561323
TI  - Extrapyramidal reactions from concurrent SSRI and atypical antipsychotic use.

PMID- 9561324
TI  - Delusional physical misidentification in the syndrome of subjective doubles.

PMID- 9561326
TI  - Progressive cerebral degeneration of childhood with liver disease (Alpers
      Huttenlocher disease) with cytochrome oxidase deficiency presenting with
      epilepsia partialis continua as the first clinical manifestation.
AB  - A previously healthy and normally developed 17-year-old young female presented
      with a sudden onset of focal motor seizure status that proved to be refractory to
      anticonvulsive treatment. Severe encephalopathy with visual impairment leading to
      blindness, mental deterioration, and predominantly left spastic tetraparesis
      developed progressively. Hepatic disease evolved 4 months after onset of the
      first symptoms and led to death in hepatic failure 1 month later. Diagnostic
      studies revealed an elevated protein and lactate in the cerebrospinal fluid, slow
      wave and intermittently continuous spike-wave activity in the EEG, and a complex
      i.v. (cytochrome-C oxidase) deficiency in the muscle biopsy. MRI scans revealed
      signal abnormalities in the occipital lobe, thalamus, and basal ganglia only
      after 3 months. Histopathological findings in liver biopsy and in postmortem
      brain examination displaying widespread predominantly right cortical spongiosis,
      neuronal loss and astrocytosis were consistent with the clinically suspected
      diagnosis of progressive neuronal degeneration of childhood with liver disease
      (PNDC) or Alpers Huttenlocher disease. This rare disorder of unknown origin is
      usually seen in infants and young children and is rarely reported in adolescence.

PMID- 9561327
TI  - Association of oligodendroglioma-like cell proliferation and angiomatous
      vasculature--coincidence or pathogenetically related lesions?
AB  - We report a case of an oligodendroglioma associated with a cavernous angioma. The
      patient, a 20-year-old man with an 8-year history of epileptic seizures,
      presented an acute onset of headache, nausea, and vomiting. Computerized
      tomographic scan and angiogram revealed multiple vascular malformations in both
      hemispheres including a cystic hemorraghic lesion with a perifocal edema
      attributing to a mass effect. Repeated puncture of the cyst failed to give
      improvement of elevated intracranial pressure. At surgery, the cyst and the
      underlying lesion were excised and found to be oligodendrocyte-rich tissue with
      malformed vascular tissue. Final histological examination revealed an
      oligodendroglioma associated with a cavernous angioma. As concurrence of
      oligodendroglioma and vascular malformation is rare, this case raises a broad
      range of differential diagnoses such as reactive oligodendroglial gliosis due to
      a vascular malformation, unusual vascularity of an oligodendroglioma as well as
      other kinds of cerebral tumors or malformations. The diagnostic difficulties as
      well as the pathogenetic and pathological significance of the concurrence of an
      oligodendroglioma and cavernous angioma are discussed.

PMID- 9561329
TI  - Factor XIIIa-immunoreactivity in tumors of the central nervous system.
AB  - The clotting factor XIIIa (FXIIIa) has been shown to be present both in tumor
      cells and in tumor-associated macrophages of different neoplasms such as
      Hodgkin's disease, giant cell tumor of bone, malignant fibrous histiocytoma,
      meningeal tumors, and hemangiopericytoma. The biological significance of these
      findings, however, are still unclear. This study investigates the
      immunohistochemical distribution of FXIIIa in 186 tumors of the central nervous
      system (CNS) in order to evaluate its possible diagnostic or prognostic
      significance in neuro-oncology. High-grade gliomas such as glioblastoma,
      gliosarcoma, astrocytoma (grade III WHO), and ependymoma (III) as well as
      meningiomas and meningeal hemangiopericytomas consistently contained factor XIIIa
      positive cells, whereas low-grade glial tumors did not do so. One desmoplastic
      medulloblastoma and one anaplastic schwannoma also showed FXIIIa-positive cells.
      With the exception of hemangiopericytomas, however, the major source of FXIIIa
      expression in all these tumors consisted of a subpopulation of tumor-associated
      macrophages, the exact role of which still remains unclear. Because of its non
      discriminatory staining in a wide variety of CNS tumors, the differential
      diagnostic contribution of FXIIIa in neuro-oncology seems to be limited.

PMID- 9561328
TI  - Solitary fibrous tumor of the meninges.
AB  - The clinical, radiologic, and pathologic features of a case of solitary fibrous
      tumor of the meninges at the base of the brain are reported. The tumor caused
      clinical symptoms in a 42-year-old Caucasian male which were indicative of
      compression of hypothalamus, basal ganglia, and third ventricle. Radiologically
      it was a large extra-axial mass isointense to brain parenchyma on precontrast T1
      weighted images that filled the suprasellar cistern and deformed the left
      cerebral peduncle. At surgery, the tumor was firm to hard and attached to dura.
      Histologically the tumor was composed of spindle-cell proliferation in a collagen
      rich background but exhibited regional variations. CD34 immunoreactivity was a
      prominent histologic finding. Ultrastructural features of meningioma, such as
      complex interdigitation of cell processes and intercellular specialized junctions
      were absent. The cells showed the typical appearances of fibroblasts with
      proximity of banded collagen and precollagen and cytoplasmic rough-surfaced
      endoplasmic reticulum. DNA ploidy analysis showed diploid DNA content. Awareness
      of this neoplasm may lead to increasingly frequent recognition and the current
      WHO classification of brain neoplasms should be modified to include this new
      entity.

PMID- 9561330
TI  - Disseminated neocortical and subcortical encephalopathy (DNSE) with widespread
      activation of brain macrophages: a new dementia disorder? Autopsy reports of two
      postmenopausal women from families with mitochondrial DNA mutations.
AB  - In this study we present 2 postmenopausal women who showed clinical symptoms that
      resembled those of a rather well-defined group of vascular dementia disorders,
      termed subcortical dementia (Binswanger disease, CADASIL). Patient 1 exhibited
      mitochondrial DNA (mtDNA) variants in the ND5 gene at position 13,708 and the
      Cytb gene at position 15,257. These DNA variants have been described in a number
      of neurologic disorders, but their pathogenetic potential is unclear. Patient 2
      showed the same DNA alterations and an additional mtDNA variant at position
      15,812 in the Cytb gene. The principal neurohistologic features of the 2 atrophic
      brains presented here include: subtotal selective neuronal cell loss in the
      cortex and, to a lesser degree, in the basal ganglia (claustrum, putamen, globus
      pallidus), sparing palaeocortex and periarchaeocortex, and a very characteristic
      and diagnostic feature was detachment of astrocytic processes from capillary
      walls resulting in pericapillary space formation. These pericapillary spaces were
      partially filled with macrophages. The spaces were not associated with total
      breakdown of the blood vessel walls as demonstrated by the absence of
      erythrocytes, lymphocytes, or polymorphonuclear leukocytes outside the vascular
      bed of the brain; progressive subcortical encephalopathy, as it is seen in
      subcortical dementia (Binswanger), but lacking arterial lipohyalinosis. The
      cerebral grey and white matter revealed cuffing of arteries and arterioles by
      adventitial macrophages. The neocortical and subcortical changes were accompanied
      by myriads of activated macrophages filled with lipids. The pathology of our 2
      cases differs from that of other neurodegenerative disorders and we suggest the
      term of "disseminated neocortical and subcortical encephalopathy (DNSE) with
      widespread activation of brain macrophages".

PMID- 9561331
TI  - Brain HIV burden and length of survival after AIDS diagnosis.
AB  - Patients with AIDS in the late stages of disease can develop dementia. Previous
      studies have suggested HIV encephalitis is the pathological substrate of HIV
      associated dementia. We hypothesized that patients who survive longer after the
      initial diagnosis of AIDS would have a higher brain HIV burden and consequently
      manifest dementia. We examined the relationship between length of survival after
      AIDS diagnosis and the presence of HIV encephalitis or HIV-associated dementia.
      We studied retrospectively the following parameters in 74 consecutive AIDS
      autopsies: length of survival after AIDS diagnosis, clinical diagnosis of
      dementia, and neuropathologic findings (including HIV burden assessment).
      Multinucleated giant cells (MNGC) were identified in 20% of the brains studied.
      HIV gp41 was detected by immunocytochemistry in 54%, approximately half of which
      had abundant HIV burden. Brains from all 4 patients who were clinically diagnosed
      with dementia and had no opportunistic neuropathologic changes contained MNGC and
      abundant HIV burden. Survival after AIDS diagnosis was significantly longer in
      patients with MNGC (p = 0.03) or abundant HIV burden (p = 0.02). A trend toward
      longer survival after AIDS diagnosis was apparent in patients with dementia, but
      did not reach statistical significance. These findings suggest that prolonged
      survival with immunosuppression may be a prerequisite for the development of HIV
      encephalitis.

PMID- 9561332
TI  - Abnormal cytoarchitecture of cortical dysplasia verified by immunohistochemistry.
AB  - Cortical dysplasia is a broad category for an abnormal structure of the cerebrum
      due to a disorder of the normal developmental process for neocortex. We
      investigated the cortical dysplastic lesions which were surgically resected from
      4 patients with intractable epilepsy. All cases showed a derangement of the
      cortical laminar structure and dysplastic changes in the neurons. In addition, 3
      of them showed large round cells (balloon cells) in the deep cortex and
      subcortical white matter. Since each lesion showed slightly different features,
      we further examined the lesions immunohistochemically by using a panel of
      antibodies against cytoskeletal proteins to recognize and classify the cortical
      dysplastic lesions. An immunohistochemical study revealed marked abnormalities of
      the cytoskeletal structures of dysplastic neurons, bizarre glial cells and
      balloon cells. These cells showed an accumulation of either phosphorylated NF,
      MAP2 or GFAP in a distinct fashion. Ubiquitin immunoreactivity highlighted the
      extent of cortical dysplastic lesions. In a young patient, we also found the
      neuronal cytoplasmic lipofuscin deposition. It is thus considered that these
      diverse immunohistochemical appearances of cortical dysplasia may thus imply a
      different pathogenesis and they should therefore be classified based on the
      extent of histological abnormalities.

PMID- 9561333
TI  - Primary epithelioid hemangioendothelioma of the clivus.
AB  - We describe the clinical, radiologic, and pathologic features of a primary
      intracranial hemangioendothelioma arising in the clivus in a 38-year-old female,
      emphasizing the importance of including this rare entity in the differential
      diagnosis of tumors arising at the base of the skull. To our knowledge, this is
      the first reported case of a clival hemangioendothelioma. Aside from its unusual
      location, this case is also notable for its apparent rapid growth and mixed
      epithelioid-spindle cell morphology. Appropriate neuroimaging studies may offer
      crucial information, ensuring that this uncommon entity is included in the
      differential diagnosis of a clival mass.

PMID- 9561334
TI  - Malignant peripheral nerve sheath tumors developing multifocally in the central
      nervous system in a patient with neurofibromatosis type 2.
AB  - We describe autopsy findings of multifocal malignant peripheral nerve sheath
      tumors (MPNSTs) appearing in the central nervous system in a 45-year-old Japanese
      female with neurofibromatosis type 2. Multiple MPNSTs were detected in both III
      and VIII, left IV, and V cranial nerves, and a number of nerve roots of the
      spinal cord. Neurofibromata were on the other hand evident on some nerve roots of
      the spinal cord and femoral and sciatic nerves. Our results suggest that a
      mutation of p53 gene may have played a role in the malignant transformation of
      nerve tumors in this patient since p53 protein was immunohistochemically detected
      in MPNST cells but not in tumor cells of the neurofibromata.

PMID- 9561336
TI  - Physiology of the nose and paranasal sinuses.

PMID- 9561335
TI  - Immunity, infection, and nasal disease.

PMID- 9561337
TI  - The role of allergy in sinus disease. Children and adults.

PMID- 9561339
TI  - Lipid mediators in inflammatory disorders.
AB  - During the past few decades, intensive collaborative research in the fields of
      chronic and acute inflammatory disorders has resulted in a better understanding
      of the pathophysiology and diagnosis of these diseases. Modern therapeutic
      approaches are still not satisfactory and shock, sepsis and multiple organ
      failure remain the great challenge in intensive care medicine. However, the
      treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis
      or psoriasis also represents an unresolved problem. Many factors contribute to
      the complex course of inflammatory reactions. Microbiological, immunological and
      toxic agents can initiate the inflammatory response by activating a variety of
      humoral and cellular mediators. In the early phase of inflammation, excessive
      amounts of interleukins and lipid-mediators are released and play a crucial role
      in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother
      substance of the pro-inflammatory eicosanoids, is released from membrane
      phospholipids in the course of inflammatory activation and is metabolised to
      prostaglandins and leukotrienes. Various strategies have been evaluated to
      control the excessive production of lipid mediators on different levels of
      biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme
      for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the
      development of receptor antagonists against platelet activating factor and
      leukotrienes. Some of these agents exert protective effects in different
      inflammatory disorders such as septic organ failure, rheumatoid arthritis or
      asthma, whereas others fail to do so. Encouraging results have been obtained by
      dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic
      acid (EPA). In states of inflammation, EPA is released to compete with AA for
      enzymatic metabolism inducing the production of less inflammatory and chemotactic
      derivatives.

PMID- 9561338
TI  - Diagnosis and treatment of acute and subacute sinusitis in children and adults.

PMID- 9561340
TI  - Antiendotoxin strategies for the prevention and treatment of septic shock. New
      approaches and future directions.
AB  - Therapy for Gram-negative sepsis remains unsatisfactory despite a concerted
      effort to develop new treatments for this common, life-threatening syndrome.
      Current research continues on several fronts to improve the treatment options
      available to clinicians in the management of these critically ill patients.
      Recently, a greater understanding of the complex molecular basis of endotoxin
      mediated pathophysiological effects in humans has generated a number of novel
      therapeutic agents for sepsis. Several of these treatment strategies have already
      entered clinical trials and it is hoped that some of these therapies will become
      widely available in the near future. In this review, the current status of the
      most promising new antiendotoxin agents is summarised, and the major obstacles to
      the successful clinical development of these therapies are described. New
      antiendotoxin therapies include those which interrupt the synthesis of endotoxin,
      bind and neutralise its activity, prevent endotoxin interactions with host
      effector cells and interfere with endotoxin-mediated signal transduction
      pathways. Potential therapeutic strategies involving these agents consist of
      endotoxin analogues, antibodies, subunit vaccines, binding columns, recombinant
      human proteins and small molecule inhibitors of endotoxin synthesis and
      intracellular signalling. The pitfalls of previous antiendotoxin clinical
      investigations and the perils of future clinical trial designs are discussed in
      the context of unmet needs and realistic expectations for success. While
      considerable progress has been made, effective and new treatments for Gram
      negative bacterial sepsis continues to elude us at the present time. This has
      been to the detriment of patients, investigators and pharmaceutical companies
      alike. It will require focused efforts by basic scientists, continued support by
      industry and enlightened study designs by clinical investigators to successfully
      develop antiendotoxin in therapies for use in septic patients in the future.

PMID- 9561341
TI  - The classification of calcium antagonists and their selection in the treatment of
      hypertension. A reappraisal.
AB  - Calcium antagonists have become one of the most important advances in the
      treatment of hypertension since their introduction over 20 years ago. The
      increase in the number of available calcium antagonists (as new formulations of
      pre-existing drugs or new chemical entities) over recent years has contributed to
      an ever-changing scenario regarding their appropriate use compared with other
      antihypertensive agents. As a consequence of this evolving situation, several
      authors have proposed a 3-generation classification of calcium antagonists
      currently, or soon to be, marketed in several counties. The classification system
      is based among other variables, on chemical structure, tissue selectivity,
      administration frequency and duration of action. In this article, this
      classification is reviewed and updated on the basis of new information that is
      available. In addition, factors which influence the selection of calcium
      antagonists in the treatment of hypertension in specific patient populations are
      discussed. As well as pharmacodynamic and pharmacokinetic considerations, these
      factors also include previous experience with particular drugs in specific
      patient populations, cost of treatment and drug interactions. Among the
      dihydropyridine calcium antagonists, the first generation compounds have been
      clearly superseded and are not recommended for use in hypertensive patients.
      Whilst the second generation agents represent an adequate treatment, third
      generation calcium antagonists possess distinct advantages. Definitive
      confirmation of the role of calcium antagonists in hypertension lies in several
      ongoing large multicentre trials.

PMID- 9561343
TI  - Hyperthyroidism. Current treatment guidelines.
AB  - Hyperthyroidism is common and affects approximately 2% of women and 0.2% of men.
      The most common cause of hyperthyroidism is Graves' disease, an autoimmune
      disorder associated with circulating immunoglobulins that bind to and stimulate
      the thyrotropin (TSH) receptor, resulting in sustained thyroid overactivity.
      Toxic nodular goitres cause hyperthyroidism due to autonomous hyperfunctioning of
      localised areas of the thyroid. There are 3 recognised modalities of treatment
      for hyperthyroidism: antithyroid drugs, surgery and radioiodine. All are
      effective but no single method offers an absolute cure. Patients with Graves'
      disease may be prescribed antithyroid drugs over a period of 12 to 18 months with
      a view to inducing a long term remission. These drugs are also often given for a
      short period to render the patient euthyroid before definitive therapy with
      radioiodine or thyroidectomy. However, antithyroid drugs will not 'cure'
      hyperthyroidism associated with a toxic nodular goitre. The use of radioiodine as
      a first-line therapy for hyperthyroidism is growing. It is well tolerated, with
      the only long term sequelae being the risk of developing radioiodine-induced
      hypothyroidism. Radioiodine can be used in all age groups other than children,
      although it should also be avoided in pregnancy and during lactation. Pregnancy
      should be avoided for 4 months following its administration. Radioiodine may
      cause a deterioration in Graves' ophthalmopathy and corticosteroid cover may
      reduce the risk of this complication. The treatment of choice for toxic nodular
      goitre hyperthyroidism is radioiodine. Surgery, either subtotal or near-total
      thyroidectomy, has limited but specific roles to play in the treatment of
      hyperthyroidism: this approach is rarely used in patients with Graves' disease
      unless radioiodine has been refused or there is a large goitre causing symptoms
      of compression in the neck. The goal of surgery is to cure the underlying
      pathology while leaving residual thyroid tissue to maintain postoperative
      euthyroidism.

PMID- 9561342
TI  - A practical guide to the management of distal ulcerative colitis.
AB  - This article reviews the role of corticosteroids, sulfasalazine and mesalazine (5
      aminosalicylic acid, mesalamine), immunosuppressive agents and alternative novel
      drugs for the treatment of distal ulcerative colitis. Short cycles of
      traditional, rectally administered corticosteroids (methylprednisolone,
      betamethasone, hydrocortisone) are effective for the treatment of mild to
      moderately active distal ulcerative colitis. In this context, their systemic
      administration is limited to patients who are refractory to either oral 5-amino
      salicylates, topical mesalazine or topical corticosteroids. Of no value in
      maintaining remission, the long term use of either or topical corticosteroids may
      be hazardous. A new class of topically acting corticosteroids [budesonide,
      fluticasone, beclomethasone dipropionate, prednisolone-21-methasulphobenzoate,
      tixocortol (tixocortol pivalate)] represents a valid alternative for the
      treatment of active ulcerative colitis, and may be useful in the treatment of
      refractory distal ulcerative colitis. Although there is controversy concerning
      dosage or duration of therapy, oral and topical mesalazine is effective in the
      treatment of mild to moderately active distal ulcerative colitis. Sulfasalazine
      and mesalazine remain the first-choice drugs for the maintenance therapy of
      distal ulcerative colitis. Evidence exists showing a trend to a higher remission
      rate with higher doses of oral mesalazine. Topical mesalazine (suppositories or
      enemas) also is effective in maintenance treatment. For patients with chronically
      active or corticosteroid-dependent disease, azathioprine and mercaptopurine are
      effective in reducing either the need for corticosteroids or clinical relapses.
      Moreover, they are effective for long term maintenance remission. Cyclosporin may
      be useful in inducing remission in patients with acutely severe disease who do
      not achieve remission with an intensive intravenous regimen. Existing data
      suggest that azathioprine and mercaptopurine may be effective in prolonging
      remission in these patients. The role of alternative drugs for the treatment of
      distal ulcerative colitis and its different forms is reviewed. In particular data
      are reported concerning the effectiveness of 5-lipoxygenase inhibitors, topical
      use of short chain fatty acids, nicotine, local anaesthetics, bismuth
      subsalicylate enema, sucralfate, clonidine, free radical scavengers, heparin and
      hydroxychloroquine.

PMID- 9561344
TI  - Recognition and treatment of idiopathic pulmonary fibrosis.
AB  - The diagnosis of idiopathic pulmonary fibrosis can be made only after exclusion
      of other entities such as neoplasm, toxic treatments, collagen vascular diseases,
      occupational exposure or granulomatous diseases, such as sarcoidosis. The
      repercussions on gas exchanges are the most reliable indications of the severity
      of the disease, the measure of lung volume or chest x-rays alone often being
      misleading. Biopsies obtained during transbronchial procedures by thoracoscopies
      or thoracotomy are of great help, but mainly to rule out other diseases. In many
      cases, only a high resolution computerised tomography (CT) scan and
      bronchoalveolar lavage are performed to rule out infection or tumour and to
      assess the inflammatory state of the disease. Due to the fact that barely a
      quarter of patients respond to corticosteroids alone, cytostatics (in particular
      azathioprine) are often prescribed simultaneously with low dose corticosteroids,
      either initially or after an unsuccessful trial of corticosteroids. Cyclosporin
      has been useful for only a limited number of patients. Colchicine has been shown
      useful in an open trial but its role still needs to be assessed. Anticytokine
      therapy and the role of substances such as relaxin are still at the experimental
      stage. Lung transplantation is now a therapeutic option for selected patients.

PMID- 9561345
TI  - Glimepiride. A review of its use in the management of type 2 diabetes mellitus.
AB  - Glimepiride is a sulphonylurea agent that stimulates insulin release from
      pancreatic beta-cells and may act via extrapancreatic mechanisms. It is
      administered once daily to patients with type 2 (non-insulin-dependent) diabetes
      mellitus in whom glycaemia is not controlled by diet and exercise alone, and may
      be combined with insulin in patients with secondary sulphonylurea failure. The
      greatest blood glucose lowering effects of glimepiride occur in the first 4 hours
      after the dose. Glimepiride has fewer and less severe effects on cardiovascular
      variables than glibenclamide (glyburide). Pharmacokinetics are mainly unaltered
      in elderly patients or those with renal or liver disease. Few drug interactions
      with glimepiride have been documented. In patients with type 2 diabetes,
      glimepiride has an effective dosage range of 0.5 to 8 mg/day, although there is
      little difference in efficacy between dosages of 4 and 8 mg/day. Glimepiride was
      similar in efficacy to glibenclamide and glipizide in 1-year studies. However,
      glimepiride appears to reduce blood glucose more rapidly than glipizide over the
      first few weeks of treatment. Glimepiride and gliclazide were compared in
      patients with good glycaemic control at baseline in a 14-week study that noted no
      differences between their effects. Glimepiride plus insulin was as effective as
      insulin plus placebo in helping patients with secondary sulphonylurea failure to
      reach a fasting blood glucose target level of < or = 7.8 mmol/L, although lower
      insulin dosages and more rapid effects on glycaemia were seen with glimepiride.
      Although glimepiride monotherapy was generally well tolerated, hypoglycaemia
      occurred in 10 to 20% of patients treated for < or = 1 year and > or = 50% of
      patients receiving concomitant insulin for 6 months. Pooled clinical trial data
      suggest that glimepiride may have a lower incidence of hypoglycaemia than
      glibenclamide, particularly in the first month of treatment. Dosage is usually
      started at 1 mg/day, titrated to glycaemic control at 1- to 2-week intervals to a
      usual dosage range of 1 to 4 mg/day (maximum 6 mg/day in the UK or 8 mg/day in
      the US). CONCLUSIONS: Glimepiride is a conveniently administered alternative to
      other sulphonylureas in patients with type 2 diabetes mellitus not well
      controlled by diet alone. Its possible tolerability advantages and use in
      combination with other oral antidiabetic drugs require further study. Glimepiride
      is also reported to reduce exogenous insulin requirements in patients with
      secondary sulphonylurea failure when administered in combination with insulin.

PMID- 9561347
TI  - Adolescent psychiatry: its potential to reduce the burden of mental disorder.

PMID- 9561348
TI  - Stability and change in externalising behaviours.
AB  - This paper provides an overview of a series of issues relating to continuity and
      discontinuity in externalising disorders including conduct disorder, attention
      deficit disorder and substance use disorders in childhood and adolescence. These
      issues include: (a) the assessment of stability and change; (b) the origins of
      behavioural stability; (c) the origins of behavioural change; and (d) the
      preventive and clinical implications of research into behavioural stability and
      change. It is concluded that future research into this area should involve: (a)
      further research into the genetic factors underlying externalising disorders; (b)
      continued research into the developmental progressions; (c) refinement and
      revision of measurement methodologies; and (d) greater use of designed
      experimentation to examine the extent to which externalising behaviours are
      amenable to change through both public health and clinical interventions.

PMID- 9561346
TI  - Liposomal amphotericin B. Therapeutic use in the management of fungal infections
      and visceral leishmaniasis.
AB  - Incorporation of amphotericin B into small unilamellar liposomes (AmBisome)
      alters the pharmacokinetic properties of the drug, but allows it to retain
      significant in vitro and in vivo activity against fungal species, including
      Candida, Aspergillus and Cryptococcus, and parasites of the genus Leishmania.
      Used as prophylaxis against fungal infections in immunocompromised patients,
      liposomal amphotericin B appeared to reduce the incidence of both fungal
      colonisation and proven fungal infections, but did not affect overall survival.
      Empirical therapy with liposomal amphotericin B in immunocompromised adults or
      children with suspected fungal infections was at least as effective as therapy
      with conventional amphotericin B. In the largest noncomparative studies,
      liposomal amphotericin B produced mycological eradication in 40 and 83% of
      patients with proven Candida infections and 41 and 60% with proven Aspergillus
      infections; however, these studies included relatively few patients. Mycological
      eradication rates of 67 to 85% in patients with cryptococcal meningitis have been
      reported. Liposomal amphotericin B is an effective treatment for visceral
      leishmaniasis in immunocompetent adults and children, including those with severe
      or drug-resistant disease. The drug also produces good response rates in
      immunocompromised patients; however, relapse rates in these patients are high.
      Liposomal amphotericin B is generally well tolerated. Few patients require
      discontinuation or dose reduction of the drug because of adverse events. The most
      frequently reported adverse events are hypokalaemia, nephrotoxicity and infusion
      related reactions; however, these occur significantly less often after liposomal
      amphotericin B than after the conventional formulation of the drug. The
      acquisition cost of liposomal amphotericin B is higher than that of conventional
      amphotericin B. Cost-effectiveness analysis did not clearly show an economic
      benefit for empirical liposomal amphotericin B antifungal therapy in adults;
      however, one model suggested that initial empirical therapy with the liposomal
      formulation in children may cost less per cure than initial therapy with the
      conventional formulation. Liposomal amphotericin B appears to be an effective
      alternative to conventional amphotericin B in the management of immunocompromised
      patients with proven or suspected fungal infections. Use of the drug is
      facilitated by its greatly improved tolerability profile compared with
      conventional amphotericin B. Because of this, liposomal amphotericin should be
      preferred to conventional amphotericin B in the management of suspected or proven
      fungal infections in immunocompromised patients with pre-existing renal
      dysfunction, amphotericin B-induced toxicity or failure to respond to
      conventional amphotericin B. Liposomal amphotericin B may also be considered for
      first- or second-line treatment of immunocompetent patients with visceral
      leishmaniasis.

PMID- 9561349
TI  - Increased rates of psychosocial disorders in youth.
AB  - The evidence for an increased incidence of rates of psychosocial disorders
      including depression, suicide, delinquency, eating disorders, and drug and
      alcohol abuse is summarized. Findings from prospective studies, family genetic
      studies, community surveys, repeated cross-sectional surveys, and data from
      mortality and police statistics suggest that the increase over time of several of
      these disorders is supported by epidemiological evidence, particularly for
      suicide, delinquency, addictive behaviors, and depression. Several studies also
      indicate that an earlier age of onset for these disorders is seen in the most
      recent birth cohorts, with most of these disorders having their onset in
      adolescent years. The implications of these findings for child psychiatric
      treatment and services are discussed.

PMID- 9561350
TI  - "A stitch in time" ... the scope for preventive strategies in early psychosis.
AB  - Preventive endeavours in psychotic disorders have been hampered by many obstacles
      over the past century. One important barrier has been the corrosive pessimism
      which has attached to the treatment prospects for schizophrenia in particular
      since the time of Kraepelin, and the isolation of this disorder from progressive
      models of preventive intervention which operate in general health care. This
      paper outlines a rationale, logic and model for realistic preventive efforts in
      early psychosis, focusing on indicated prevention in the pre-psychotic phase and
      early intervention from the onset of frank psychotic symptoms through the early
      years of illness. The latter is discussed through a series of clinical challenges
      which will be familiar to clinicians during this phase of illness. The existing
      evidence is introduced and the gaps indicated. It is argued that the case for a
      preventive approach possesses more than face validity alone, and that momentum is
      building for a significant paradigm shift. If this to be securely based and
      durable, it will need to become increasingly evidence based and demonstrate cost
      effectiveness. The nature of the evidence and the strategy for its assembly are
      also considered.

PMID- 9561351
TI  - Prevention and early intervention for depression in adolescence and early adult
      life.
AB  - Over the past decade there has been increasing interest in the possibility that
      early intervention might prevent mental disorders later in life. Indeed, in the
      United Kingdom the Department of Health recommends that health promotion should
      be one of the main functions of child mental health services, a suggestion that
      has been endorsed by professional bodies. It is easy to see why both purchasers
      and providers of mental health services would be interested in prevention, but
      will preventive interventions work in practice? This paper discusses the
      possibility of preventing depressive disorder in late adolescence and early adult
      life by intervening in childhood and early adolescence. The paper begins with a
      description of the phenomenology of depression and its risk factors. It then goes
      on to describe a framework of prevention and within this framework explores
      whether there is an adequate knowledge base. The general perspective that is
      presented is one of cautious scepticism. It is argued that difficulties in
      defining depression and identifying risk factors that can easily be remedied make
      it unlikely that within the foreseeable future primary prevention programmes will
      prove to be more effective than treatment and rehabilitation of affected
      individuals. The possibility that preventive programmes could do harm will also
      be discussed. The paper concludes with some proposals about appropriate targets
      for prevention. It is suggested that apart from a few policy areas where there
      are some relatively harmless measures that could protect from later depression, a
      balanced preventive programme will give higher priority to treatment services
      than to those concerned with early intervention.

PMID- 9561352
TI  - Differentiation of autonomic nervous activity in different stages of coma
      displayed by power spectrum analysis of heart rate variability.
AB  - The analysis of heart rate (HR) variability offers a noninvasive method to
      investigate autonomic nervous system activity in comatose patients. We analyzed
      three components of the HR variability in a group of comatose patients: the low
      frequency band (LF), representing mainly sympathetic influence, the mid-frequency
      band (MF), representing sympathetic and parasympathetic influence, and the high
      frequency band (HF), representing the parasympathetic influence. A value for
      sympathovagal balance was defined as LF/HF and MF/HF ratio. Moreover, the skin
      conductance level (SCL) and the skin conductance resistance (SCR) variability
      were recorded. The patient group consisted of 22 patients with traumatic brain
      injuries. Coma depth was assessed by the Glacow Coma Scale and artifact-free HR,
      SCL, and SCR were measured 75 times in the patient group. The results documented
      a significant gain in sympathetic nervous system activity corresponding with the
      state of emerging from coma. This gain was most pronounced in the HF component of
      the HR and in the sympathovagal balance between LF/HF. The findings in SCL and
      SCR variability endorsed this result. It is concluded that emerging from coma is
      accompanied by an increasing influence of the sympathetic nervous system on HR
      control. This leads to a change in the sympathovagal balance, i.e., a
      reintegration of parasympathetic and sympathetic activity.

PMID- 9561353
TI  - Quantitative proton magnetic resonance spectroscopy of the basal ganglia in
      patients with affective disorders.
AB  - Proton magnetic resonance spectra were recorded from a subcortical region
      containing the basal ganglia in 40 patients with affective disorders (18 with
      bipolar disorder and 22 with major depression) and in 20 normal controls. The
      absolute concentration of the choline-containing compounds (Cho) in the patients
      with bipolar disorder in the depressive state was significantly higher than that
      in the normal controls. The patients with bipolar disorder had significantly
      higher levels of the Cho/creatine + phosphocreatine (Cr) and Cho/N-acetly-1
      aspartate (NAA) peak ratio compared with the normal controls in both the
      depressive and euthymic states, with a tendency to higher levels in the
      depressive state. The Cho/NAA peak ratio was also significantly higher in the
      patients with major depression compared with the normal controls. These results
      suggest that the membrane phospholipid metabolism in the basal ganglia is altered
      in affective disorders.

PMID- 9561354
TI  - Visual fields after removal of subretinal hemorrhages and neovascular membranes
      in age-related macular degeneration.
AB  - BACKGROUND: Surgical removal of subretinal hemorrhaging and membranes in eyes
      with age-related macular degeneration is feasible from a technical point of view,
      but no advantage over the spontaneous course of the disease has been proven.
      Visual acuity usually does not improve much. A realistic aim of surgical
      intervention may be diminution of the central scotoma size, which has not been
      studied. METHOD: In a prospective study visual fields were measured
      preoperatively and 6 weeks and 6 months postoperatively in eyes operated on for
      subretinal hemorrhages and membranes in exudative age-related macular
      degeneration. The OCTOPUS 1-2-3 program glx, which tests the visual field of 60
      degrees diameter at 59 points, was used. Changes in the total size of areas with
      sensitivity loss of 10-20 dB (= relative scotoma) and > 20 dB (= absolute
      scotoma) were interpreted as surgical effect. Patients with postoperative retinal
      detachment or neovascular recurrence were excluded. 30 eyes of 29 patients were
      enrolled (mean age 75.3 years, 11 male, 18 female) and divided into 3 groups: 14
      eyes with massive subretinal hemorrhage of diameters > 30 degrees; 12 eyes with
      hemorrhages of 10 degrees-30 degrees; 4 eyes with mere neovascular membranes < 10
      degrees. RESULTS: (1) The visible area of damage is diminished by surgery (P <
      0.01). The reduction for lesions > 30 degrees is 80%; for lesions between 10
      degrees and 30 degrees the improvement is 43%. For lesions < 10 degrees there is
      no significant change. (2) The absolute scotoma size diminishes in all three
      groups (P = 0.05). The reductions are 63%, 57% and 21%, respectively. (3) Areas
      of absolute scotoma do not regain full function but are converted to relative
      scotoma depth, at best. Therefore, in the > 30 degrees group an overall increase
      (P < 0.01) of the relative scotoma size is observed. (4) The mean sensitivity in
      the 60 degrees field enhances by 1.6 dB (average over 30 eyes, P = 0.04). (5)
      Mean preoperative visual acuities were 0.03, 0.12 and 0.17, respectively, with no
      significant change after surgery. The power of testing is sufficient (0.93) to
      reject an increase of acuity from 0.12 to 0.2 in group 2. CONCLUSIONS: For
      hemorrhagic subretinal lesions of diameter > 10 degrees a relevant reduction of
      central scotoma size is achieved by surgery. The final benefit for the patients
      depends on the frequency of surgical complications and neovascular recurrence.

PMID- 9561355
TI  - Ultrastructure of epiretinal membranes associated with macular holes.
AB  - BACKGROUND: The role of tangential traction exerted by epiretinal membranes in
      the pathogenesis of macular holes is not fully understood. Furthermore, the role
      of glial cells in the formation and/or closure of macular holes remains to be
      elucidated. METHODS: To better understand the pathogenesis of macular hole
      formation and to compare the ultrastructural features of epiretinal membranes
      associated with macular holes of primary and secondary etiology, we harvested 23
      translucent epiretinal membranes associated with macular holes stages III-IV at
      the time of pars plana vitrectomy and examined them electron microscopically.
      Eighteen membranes were obtained from patients with idiopathic macular holes. 3
      membranes from patients with myopic macular holes and 2 epiretinal membranes were
      associated with macular holes which had developed after retinal detachment
      surgery. RESULTS: Eighteen membranes contained a continuous undulating piece of
      inner limiting lamina (ILL). Sixteen of 18 epiretinal membranes at the margins of
      idiopathic macular holes, 2 of 3 membranes in myopic macular holes and both
      membranes associated with a macular hole after retinal detachment surgery
      demonstrated mono- or multilayers of fibrous astrocytes with single macrophage-
      or fibrocyte-like cells. Vitreous and newly formed collagen occupied the space
      between the ILL and the glial cells. Three macular holes were surrounded by
      rather firmly attached acellular ILL. CONCLUSIONS: Glial cells and newly formed
      collagen may play an important role in macular hole formation by exerting
      tangential traction regardless of the underlying disease process. Glial cells,
      however, may also be involved in healing of the retinal defect and pars plana
      vitrectomy with peeling of an epiretinal membrane, and/or the ILL may induce
      directed glial cell proliferation and migration. The similar ultrastructure of
      epiretinal membranes associated with macular holes and "simple epiretinal
      membranes" as described by Foos [8] suggests a common pathogenesis for macular
      holes and macular pucker.

PMID- 9561356
TI  - Results of penetrating keratoplasty in bullous silicone oil keratopathy.
AB  - BACKGROUND: To evaluate the results of penetrating keratoplasty (PK) in bullous
      silicone oil keratopathy (BSK). MATERIAL AND METHODS: PK for BSK was performed in
      13 patients, aged from 31 to 82 years. In all patients, pars plana vitrectomy
      (PPV) with silicone oil implantation (SOI) had been previously performed as the
      definitive surgery: for complicated retinal detachment with advanced
      proliferative vitreoretinopathy in 12 eyes and for diabetic traction detachment
      in one eye. Seven patients were monocular. All 13 eyes were aphakic and there was
      a long-lasting contact of silicone oil with the corneal endothelium. Before
      keratoplasty, each eye underwent between two and five operations, on average
      three, for retinal detachment or late complications of SOI. The interval between
      SOI and PK was from 11 to 79 months. The patients were followed up for 12-52
      months. RESULTS: At the last follow-up examination, a clear graft was found in 6
      out of 13 eyes (46%). The six clear grafts were found in the ten eyes where
      silicone oil had been removed before keratoplasty. The graft became opaque in all
      three eyes in which silicone oil had not been removed. Six out of seven eyes with
      failed grafts atrophied. Visual acuity improved in all six eyes with the clear
      graft from had movement preoperatively to 0.05-0.25. The decreased visual acuity
      was caused by irreparable damage to the macula, which resulted from high myopia,
      proliferative vitreoretinopathy or long-lasting detachment of the macula.
      CONCLUSIONS: PK in BSK was successful only in those eyes in which the attached
      retina enabled the removal of the silicone oil before the PK. The reattached
      retina and useful visual acuity before the development of BSK were the
      preconditions for functional success of the PK.

PMID- 9561357
TI  - Prognostic value of the pattern electroretinogram in cases of tumors affecting
      the optic pathway.
AB  - BACKGROUND: Tumors compressing the optic pathway may lead to irreversible loss of
      vision which may be detected by the pattern electroretinogram (PERG) because of
      its relation to ganglion cell function. METHODS: Eyes of 19 patients were tested
      shortly before and 5-10 days after tumor surgery. Visual acuity, the 30-deg
      visual field and the transient and steady-state pattern reversal ERG were
      measured. RESULTS: Using patterns of 1.5 x 1.2 deg there was a good correlation
      between the change of pre- and post-surgical visual performance and most of the
      pattern ERG amplitudes. For all variables tested--P50, N95- and steady-state
      amplitude--there was a critical value beyond which the visual outcome could be
      bad or favorable, whereas patients showing higher amplitudes always remained
      stable or improved after surgery. CONCLUSION: The positive correlation between
      pattern ERG amplitudes and the post-surgical outcome in the case of tumors
      affecting the optic pathway may be helpful in predicting the outcome for these
      patients.

PMID- 9561358
TI  - Progression of retinopathy and alteration of the blood-retinal barrier in
      patients with type 2 diabetes: a 7-year prospective follow-up study.
AB  - BACKGROUND: The study was carried out to evaluate the correlation between blood
      retinal barrier (BRB) permeability and the progression of diabetic retinopathy
      (DR), defined by development of "need for photocoagulation", over a 7-year period
      by means of vitreous fluorometry (VF). METHODS: Forty type 2 diabetic patients
      with minimal or no retinopathy, aged 40-65 years (mean 53.9 + 7.3 years), were
      followed up prospectively for 7 years. Investigations including standard
      ophthalmological examination, fundus photography, fluorescein angiography and VF
      were performed at entry and 1, 4, 5 and 7 years later. Only one eye per patient
      was included in the study. Need for photocoagulation was based on Early Treatment
      Diabetic Retinopathy Study protocols and decided by the attending
      ophthalmologist. RESULTS: After 7 years of follow-up a total of 22 of the 40 eyes
      had received photocoagulation. The eyes that needed photocoagulation were those
      that had higher VF values at the entry of the study and showed higher rates of
      deterioration (initial values 5.1 + 1.9 vs 2.8 + 1.5 x 10(-6) min-1, P < 0.001;
      annual increase in leakage for the first year, 1.5 + 0.8 vs 0.5 + 1.0 x 10(-6)
      min-1, P < 0.001,). The eyes that did not need photocoagulation during the 7
      years of follow-up showed stable VF readings (-0.1 + 1.2 x 10(-6) min-1,
      difference between initial values and 7 years later). CONCLUSIONS: Abnormally
      high VF values and their rapid increase over time are good indicators of
      progression and worsening of the retinopathy in diabetes type 2.

PMID- 9561359
TI  - Age-related deterioration of motion perception and detection.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of aging on motion
      detection and perception. METHODS: Forty-six subjects, ages 19-92 years, were
      asked to view a motion stimulus. Infrared oculography was used to objectively
      evaluate motion detection by documenting the presence of optokinetic nystagmus as
      the subjects viewed the stimulus. Subjective responses to motion perception were
      recorded using a computer joystick. RESULTS: Optokinetic nystagmus was clearly
      detectable in all 46 subjects. Motion detection and perception thresholds showed
      age-related deterioration. No relationship was found to gender or age-gender
      interaction. CONCLUSION: The results indicate motion detection and perception
      thresholds deteriorate with age. This may reflect a susceptibility to age-related
      degeneration in specific cortical areas responsible for motion perception as well
      as neurodegeneration in the retinogeniculate pathway.

PMID- 9561360
TI  - Reproducibility of measurements with a new slit lamp-mounted ocular blood flow
      tonograph.
AB  - PURPOSE: To assess the reliability of measurements of intraocular pressure
      (i.o.p.), pulse amplitude (PA), and pulsatile ocular blood flow (POBF) and the
      validity of measurements of IOP with a new ocular blood flow tonograph. METHODS:
      Intraocular pressure pulse was assessed with pneumatic tonometry. In this study,
      we used the OBF Labs ocular blood flow tonograph with two different pneumatic
      probes, a modified Langham probe and a newly developed probe. One ophthalmologist
      compared two machines, first with the modified Langham probe and secondly with
      the newly developed probe (40 volunteers). Additionally, two ophthalmologists
      performed measurements on different days and in different sequence (34
      volunteers). Furthermore, results of IOP measurements performed with this
      tonograph were compared to those of Goldmann applanation tonometry (213
      volunteers). RESULTS: Using the modified Langham probe, POBF and PA were
      associated with the machine used for the test. However, using the newly developed
      pobe, no relevant or statistically significant differences were found for any
      variables, and reliability coefficients were between 0.70 and 0.90. Linear
      regression analysis of the Goldmann applanation tonometer on the measurements of
      IOP with the tonograph showed a regression coefficient of 0.765. CONCLUSIONS:
      Results of measurements performed with this ocular blood flow tonograph and the
      newly developed probe are expected to be reliable and comparable.

PMID- 9561362
TI  - Retinal sensitivity measurement over drusen using scanning laser ophthalmoscope
      microperimetry.
AB  - BACKGROUND: Retinal sensitivity over drusen was examined using a scanning laser
      ophthalmoscope to confirm a previous report of no change in sensitivity over
      drusen. METHODS: Microperimetry was performed using a scanning laser
      ophthalmoscope in 23 eyes of 19 subjects. Subject age ranged from 42 to 86 years
      (mean 68.5 years). Fifty-four drusen bigger than the diameter of a major retinal
      vein at the optic disc rim were examined, and drusen were classified as soft
      drusen and other large drusen. RESULTS: Nine eyes of eight subjects showed a
      decrease in retinal sensitivity over drusen. The decrease in retinal sensitivity
      was more than 5 dB less than the sensitivity at a peripheral non-drusen area
      peripheral to the measurement point. The sensitivity decrease was noted over 15
      of 29 large drusen and the decrease was statistically significant (P < 0.02).
      However, no relationship between the size of the drusen and the amount by which
      sensitivity decreased was found. Nevertheless, a decrease in retinal sensitivity
      was not seen over any of 25 soft drusen. CONCLUSION: Large drusen may influence
      retinal sensitivity and function.

PMID- 9561361
TI  - Seroprevalence of anti-Borrelia antibodies among patients with confirmed
      sarcoidosis in a region of Japan where Lyme borreliosis is endemic.
AB  - BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease of unknown
      etiology, while Lyme borreliosis is a multisystemic disorder caused by Borrelia
      burgdorferi. The purpose of this study is to evaluate the relationship between
      sarcoidosis and Lyme borreliosis in a region of Japan where Lyme borreliosis is
      endemic. METHODS: We determined the seroprevalence of anti-Borrelia burgdorferi
      antibodies as well as antibodies three Japanese Borrelia strains by enzyme-linked
      immunosorbent assay and dotblot assay using purified Borrelia-specific proteins
      in 46 patients with confirmed sarcoidosis and 150 controls (50 disease controls
      and 100 healthy controls) in Hokkaido, the affected region. RESULTS: Fifteen
      patients with sarcoidosis (32.6%) tested positive for Borrelia spirochete in both
      assays, compared with two disease controls (4.0%) and two healthy controls
      (2.0%). The seroprevalence of anti-Borrelia antibodies in patients with
      sarcoidosis was much higher in the affected region than in the region in our
      previous study were Lyme borreliosis is non-endemic. CONCLUSION: In a region
      where Lyme borreliosis is endemic, Borrelia infection may be partially associated
      with sarcoidosis.

PMID- 9561363
TI  - Granular corneal dystrophy: treatment with soft contact lenses.
AB  - Perforating keratoplasty was performed in both eyes of two siblings (sister and
      brother) with typical granular corneal dystrophy. Three of the operated eyes
      showed a recurrence of the underlying disease. In one eye, a recurrence could not
      be detected 14 years after the operation. This eye had been fitted with a contact
      lens 16 months after keratoplasty because of aphakia. Thus a contact lens may
      have a therapeutic effect in this primary epithelial disease.

PMID- 9561364
TI  - Expression of basic fibroblast growth factor and its receptor mRNA in retinal
      tissue following ischemic injury in the rat.
AB  - BACKGROUND: Our purpose was to determine the time-dependent changes of expression
      of basic fibroblast growth factor (bFGF) and its receptor in pressure-induced
      retinal ischemia in rats. METHODS: Retinal ischemia was induced in Wistar rats by
      increasing the intraocular pressure to 110 mmHg for 45 min by cannulation into
      the eyes. At the end of the ischemic period, reperfusion of the retinal
      vasculature was confirmed. Localization of bFGF and FGF receptor-1 (FGF-R) mRNAs
      were evaluated by in situ hybridization at various times after reperfusion. The
      reverse-transcription polymerase chain reaction (RT-PCR) method was used to
      detect the expression of bFGF and FGF-R mRNA in the sensory retina. RESULTS: In
      normal sensory retina, bFGF and FGF-R mRNAs were observed in the ganglion cell
      layer and inner nuclear layer. bFGF gene expression in the sensory retina
      increased within 24 h, particularly at 6-12 h. FGF-R gene expression increased
      earlier than that of bFGF. By RT-PCR, expression of bFGF gene reached a peak at 6
      24 h, and FGF-R reached a peak at 3-12 h. These RT-PCR results are comparable to
      those of in situ hybridization. CONCLUSIONS: These results demonstrate that
      transient retinal ischemia leads to the induction of bFGF mRNA synthesis, and
      suggest that bFGF has a protective role, e.g., a defense mechanism for the
      sensory retina.

PMID- 9561365
TI  - The effect of intraocular pressure on the absorption of air from the vitreous
      cavity.
AB  - BACKGROUND: The duration of an intraocular gas bubble used in vitreoretinal
      surgery is an important determinant of the safety and effectiveness of
      intraocular gas use. Considerable variability impedes the clinical determination
      of this parameter. The aim of the study was to study experimentally the
      relationship between intraocular pressure (i.o.p.) and the absorption of an
      intravitreal air bubble. METHODS: We compared the rate of absorption of an
      intravitreal air bubble in rabbit eyes that had been treated with
      cyclocryotherapy (n = 17) to the absorption of air bubbles in untreated fellow
      eyes (n = 17). RESULTS: Intravitreal air bubble persisted longer in the
      cyclocryotherapy-treated rabbit eye (mean +/- SD 78 +/- 16 h) than in the control
      fellow eyes (43 +/- 15 h). This difference was statistically significant (P <
      0.001). The length of time an air bubble persisted could be predicted from the
      IOP. CONCLUSIONS: The reason for the increased length of time an air bubble
      remained in cyclocryotherapy-treated eyes is probably the result of several
      factors, including primarily reduced aqueous flow and reduced IOP. Our results
      show that the duration of air injected into the vitreous cavity correlated to
      IOP. In addition to other known factors, the IOP should be considered in
      predicting intravitreal gas persistence.

PMID- 9561366
TI  - The lens influences aqueous humor levels of transforming growth factor-beta 2.
AB  - BACKGROUND: Transforming growth factor-beta 2 (TGF-beta 2) is a pluripotent
      cytokine which has been suggested to play a number of roles in ocular physiologic
      and pathologic states. Intraocular fluid (i.o.f.) levels of TGF-beta 2 are quite
      high. Although the sources of ocular TGF-beta are not completely defined, the
      retinal pigment epithelium, the epithelium of the ciliary body and trabecular
      meshwork cells all secrete it. In this study we utilized canine lens and rabbit
      ciliary pigmented epithelial cell cultures to quantitate the in vitro secretion
      of TGF-beta 2. In addition, the effects of aphakia or the presence of cataractous
      lenses on IOF TGF-beta 2 levels were determined. METHODS: Lens and ciliary body
      epithelial cell culture supernatants and aqueous humors were assayed for total
      TGF-beta 2 levels by ELISA and bioassay. RESULTS: TGF-beta 2 accumulated in the
      media bathing lens epithelial cell cultures (0.7 +/- 0.03 ng/ml at day 2) and
      ciliary pigmented epithelial cell cultures (0.8 +/- 0.06 ng/ml at day 2) in a
      time-dependent manner. Surprisingly, aqueous humor from aphakic rabbit eyes
      contained significantly higher levels of TGF-beta 2 than their contralateral
      phakic controls. Furthermore, aqueous humor from canine eyes with cataracts also
      contained significantly higher levels of TGF-beta 2 than normal eyes.
      CONCLUSIONS: These results suggest that the lens secretes TGF-beta 2 and that the
      presence and status of the lens may influence IOF TGF-beta 2 levels.

PMID- 9561367
TI  - A sensitive method for testing the quality of organ culture media and of
      individual medium components in a cornea bank.
AB  - BACKGROUND: It has been suggested that variations in the quality of organ culture
      preservation media are responsible for variations in early postoperative graft
      morphology. Spates of such variations have been observed repeatedly for short
      periods. This paper reports the results of a series of grafts with low
      postoperative clearing observed during a period of 6 weeks. Simultaneously,
      preoperative phase-contrast microscopy evaluation of the corneal endothelium
      revealed that an unusually large proportion of donor corneae were unsuitable for
      transplantation. METHODS: The corneal storage media were therefore rigorously
      screened, paying particular attention to specific components and properties of
      the medium, including L-glutamine, amphotericin B, water quality, pH, and the
      glassware used. Possible toxic effects were identified by means of a sensitive
      growth assay performed using isolated human corneal endothelial cells. RESULTS:
      The evaluation demonstrated that both the water quality and the L-glutamine which
      had been used for preparation of the medium were substandard during the period in
      which poor clinical results were obtained. CONCLUSION: It is recommended that
      cornea banks undertaking long-term organ culture use standardized protocols and
      carefully monitored equipment. The quality of the basal media and supplements
      should be routinely checked.

PMID- 9561368
TI  - Mature dendritic cells respond to SDF-1, but not to several beta-chemokines.
AB  - Immature dendritic cells (DCs) are highly motile, but after differentiation they
      stop migration. Chemokines are chemotactic cytokines that direct leukocyte
      trafficking, therefore we looked for the expression and function of chemokine
      receptors in immature and mature DCs. As a model, we used the human DCs that
      develop from CD14+ peripheral blood monocytes cultured with GM-CSF and IL-4.
      After 6-7 days in culture, these cells have the characteristics of immature DCs,
      but can be induced to mature further by inflammatory stimuli or by monocyte
      conditioned medium (MCM). Immature DCs express mRNA for CXCR4, CCR3 and CCR5. The
      receptors are expressed on the cell surface, as assessed with monoclonal
      antibodies, and are functional (with the exception of CCR3) as assessed by CA++
      mobilization in response to specific chemokines. Further differentiation and
      maturation of DC in MCM causes a downregulation of expression and function of the
      beta-chemokine receptors, while CXCR4 still remains, and signals a calcium flux
      on mature DCs. We argue that the downregulation of beta-chemokine receptors
      during maturation helps to stop DC movement after T cells have been identified in
      lymphoid organs or at sites of delayed-type hypersensitivity.

PMID- 9561369
TI  - Comparative analysis of dendritic cells derived from blood monocytes or CD34+
      hematopoietic progenitor cells.
AB  - In human tissues different populations of dendritic cells (DC) emerge from
      hematopoietic progenitor cells (HPC) in the bone marrow, with the intermediate
      steps of differentiation not being completely understood. In vitro, DC can be
      directly obtained from HPC or from blood monocytes (MO) cultured in the presence
      of GM-CSF and additional cytokines. We compared the antigenic profile of DC
      derived from either MO or HPC and studied their capacity to stimulate naive
      lymphocytes (LY) in the allogeneic mixed lymphocyte reaction. Both types of DC
      expressed high levels of CD1a, MHC class II, CD80, CD86 and CD40 and were potent
      stimulators of LY proliferation. DC of HPC origin, though, induced a stronger
      mixed lymphocyte reaction than MO-derived DC and showed a slightly higher average
      expression of costimulatory antigens. Low-level expression of CD14 did not
      negatively correlate with DC function on DC stimulated with lipopolysaccharide
      and was even slightly higher expressed on DC differentiating from HPC than on DC
      from CD14+ MO.

PMID- 9561370
TI  - Human dendritic cells express functional interleukin-7.
AB  - Interleukin-7 (IL-7) supports the proliferation of mature T lymphocytes, however,
      the cellular source of IL-7 for T lymphocyte activation has not been well
      established. We therefore investigated whether human peripheral blood dendritic
      cells (DC) produce IL-7 as a contribution towards T lymphocyte activation. Human
      CMRF-44+/CD14-/CD19- low density DC, purified after overnight tissue culture,
      contained IL-7 transcripts, detected by direct cell reverse transcription
      polymerase chain reaction. Intracytoplasmic staining confirmed IL-7 protein in at
      least a subpopulation of cultured low density DC. In contrast, resting/immature
      DC, isolated directly by immunodepletion of lineage marker positive cells,
      contained no IL-7 mRNA. Thus, the expression of IL-7 by DC follows the pattern
      described previously for CD80, CD86 and CD40. However, tissue culture of purified
      resting/immature DC, in contrast to CD80, CD86 and CD40, failed to induce IL-7
      transcripts. The functional importance of DC IL-7 expression was demonstrated in
      an allogeneic mixed leukocyte reaction (MLR). Neutralising mAb to IL-7
      significantly inhibited T lymphocyte proliferation when low DC numbers were used,
      but at higher stimulator numbers, anti-IL-7 mAb failed to inhibit an allogeneic
      MLR. This suggests, that when DC are in excess, other co-stimulatory pathways can
      compensate for the lack of IL-7. Addition of IL-7 to a MLR caused a significant
      increase in the proliferative response stimulated by monocytes and B lymphocytes
      but not by DC. These data support the concept of an initial phase of antigen
      uptake by DC followed by the optimisation of DC co-stimulatory potential. The co
      stimulatory repertoire expressed, including IL-7, may be regulated by exogenous
      stimuli, thereby ensuring DC flexibility in mounting a response appropriate to
      the environmental changes.

PMID- 9561371
TI  - Specific autologous anti-melanoma T cell response in vitro using monocyte-derived
      dendritic cells.
AB  - Dendritic cells (DC) are antigen-presenting cells initiating primary and
      secondary immune responses. Since malignant tumors are able to escape immunologic
      control, DC might be prime candidates to activate the immune system against tumor
      cells. In an autologous system, a dynamic interaction among monocyte-derived DC
      (MoDC), T lymphocytes, and tumor cells obtained from melanoma patients could be
      noted. MoDC were generated from blood monocytes in the presence of GM-CSF, IL-4,
      and IFN-gamma. T cells were isolated either from peripheral blood or from lymph
      nodes. Melanoma cells were harvested from surgically removed tumor metastases.
      They were then gamma-irradiated and co-cultured with autologous MoDC and T
      lymphocytes. After 5 days, the lymphocytes showed a high proliferative activity
      and the majority of them were CD8-positive. In five cases tested, they revealed a
      high cytotoxic activity resulting in apoptosis of tumor cells. These findings
      suggest that MoDC are capable of initiating an effective specific anti-tumor
      response in a strictly autologous mixed lymphocyte tumor culture (MLTC), even
      though tumor-specific antigens had not been individually defined. Therefore (I)
      whole melanoma cells can serve as a source of antigen, (II) monocyte-derived
      dendritic cells may process and present melanoma-specific antigens resulting in a
      strong lymphocyte proliferation, (III) the majority of responding T lymphocytes
      are CD8-positive, and (IV) an acquired cytotoxic response eventually leads to
      apoptosis of the melanoma cells. The reaction demonstrated here permits to in
      vitro and quantitatively monitoring the effect of T cell directed immunotherapies
      such as the adoptive immunotherapy of tumors.

PMID- 9561372
TI  - Focussing human B cell specificity by immunoselection via antigen-presenting
      cells in vitro.
AB  - We present a protocol for in vitro immunization of B cells using monocyte-derived
      accessory cells (MoAC). MoAC are developed from human peripheral blood monocytes
      in culture and represent functionally competent inducers of antigen-specific
      immune responses. Using MoAC, we attempted to immunoselect TT-specific
      lymphocytes by rosetting. Adherent human MoAC were pulsed with tetanus toxoid
      (TT) and allowed to form clusters with autologous lymphocytes, followed by
      removal of non-adherent cells. After one week of culture, a specific anti-TT
      antibody response emerged on a low background of unspecific Ig. In comparison,
      cultures which had not been selected for adherent cells produced a high
      polyclonal background. Our results demonstrate that from peripheral blood cells,
      previously not a favourable source for in vitro immunization, in a majority of
      tests antigen-specific B cells could efficiently be immunoselected via adherence
      to autologous antigen-presenting cells, leading to a high-titre in vitro
      immunization.

PMID- 9561373
TI  - The distinctive features of influenza virus infection of dendritic cells.
AB  - CD8+ cytolytic T lymphocytes (CTLs) are considered to be critical mediators for
      resistance to influenza virus infection. We have previously demonstrated that
      dendritic cells are potent antigen presenting cells in the development of anti
      influenza CTLs. Here we identify distinctive features of the interaction of
      influenza virus with dendritic cells. Exposure of dendritic cells to influenza
      virus at MOIs of 2-4:1 leads to > 90% infection, as manifested by the expression
      of the viral proteins HA and NS1. The infection is non-toxic as viral protein
      expression is sustained for > 2 days with retention of viability, but little
      infectious virus is produced. Substantial induction of the anti-viral cytokine
      IFN-alpha also occurs. Influenza infection of macrophages also results in viral
      protein expression in a majority of cells, and synthesis of IFN-alpha. In
      contrast to dendritic cells, macrophages display evidence of apoptosis within 10
      12 hours, and the majority of cells die within 24-36 hours. During this interval
      macrophages synthesize > 10-fold higher levels of virus than dendritic cells.
      Infected dendritic cells but not macrophages, can induce substantial CTL
      responses from purified blood CD8+ T cells in the absence of exogenous cytokines
      such as IL-2. Low levels of infection (MOIs of 0.02) are sufficient to generate
      potent CTL responses. Influenza virus expressing non-cleaved HA does not elicit
      CTLs indicating that virus must access the cytoplasm of dendritic cells to
      utilize traditional class I processing pathways. These observations indicate that
      DCs are distinct in their handling of influenza virus and for the induction of
      anti-viral immunity.

PMID- 9561375
TI  - Epidermal Langerhans cell development and differentiation.
AB  - Epidermal Langerhans cells (LC) play a critical role in host defense. Still we
      know rather little about the development and functional specialization of these
      bone marrow-derived dendritic cells (DC) located in the most peripheral
      ectodermal tissue of the mammalian organism. How LC develop from their primitive
      progenitors in bone marrow and to what extent LC are related in their development
      to other lineages of the hemopoietic system is still under debate. There are
      currently 3 major areas of debate: 1) which are the signals required for LC
      development and differentiation to occur, 2) what are the (molecular)
      characteristics of the intermediate stages of LC differentiation, and 3) how are
      LC related in their development and/or function to other cells of the hemopoietic
      system? A better understanding of LC development and answers to these questions
      can be expected from recently developed technologies which allow the in vitro
      generation of DC with the typical molecular, morphological and functional
      features of LC from purified CD34+ progenitor cells under defined serum-free
      culture conditions. TGF-beta 1 was found to be an absolute requirement for in
      vitro LC development under serum-free conditions upon stimulation with the
      classical DC growth and differentiation factors GM-CSF, TNF-alpha and SCF. The
      recently identified cytokine FLT3 ligand further dramatically enhanced in vitro
      LC development and even allowed efficient in vitro generation of LC colonies from
      serum-free single cell cultures of CD34+ hemopoietic progenitor cells.

PMID- 9561374
TI  - Expression of maturation-/migration-related molecules on human dendritic cells
      from blood and skin.
AB  - Progress in dendritic cell research has been overwhelming in the past few years.
      This was made possible by the recent development of simple methods to generate
      large numbers of dendritic cells. These methods use as starting populations for
      culture either CD34+ progenitor cells from cord blood or bone marrow, or
      monocytes from peripheral blood. The latter approach is critically dependent on
      the combination of GM-CSF and interleukin 4. Such "priming cultures" yield
      populations of immature dendritic cells (CD83-/CD86 +/- /CD115+/antigen uptake
      high/antigen processing high/T cell sensitization low). In order to generate
      mature dendritic cells a subsequent "differentiation culture" has to be added
      whereby monocyte-conditioned medium appears to be the optimal stimulus for
      maturation. This results in terminally mature dendritic cells (CD83+/CD86++/CD115
      /antigen uptake low/antigen processing low/T cell sensitization high). We
      investigated the expression of some molecules involved in maturation and
      migration on human monocyte-derived dendritic cells from blood in comparison with
      dermal dendritic cells and epidermal Langerhans cells. We present a method to
      highly enrich epidermal Langerhans cells. Survival of purified Langerhans cells
      in culture is dependent on the presence of GM-CSF and TNF-alpha. During
      maturation a substantial part of the Langerhans cells loses expression of the
      cutaneous lymphocyte antigen (CLA); mature dendritic cells from the dermis are
      completely devoid of CLA. Similarly, CLA as well as CD15s (Sialyl Lewis x) and
      CD31 (PECAM-1) that can be readily detected on immature monocyte-derived
      dendritic cells are down-regulated upon maturation. CD68 expression is very low
      in cutaneous dendritic cells; in monocyte-derived dendritic cells this molecule
      is abundantly present. Subsets of monocyte-derived dendritic cells express E
      cadherin; CD87 (urokinase plasminogen activator receptor) is weakly expressed on
      both immature and mature monocyte-derived dendritic cells. Taken together, these
      data suggest that the phenotype of monocyte-derived dendritic cells (E-cadherin
      low to negative, CD68++) is not indicative for a cutaneous destiny. Furthermore,
      the downregulation upon maturation of molecules involved in migration through
      vessel walls (CD31, CLA, CD15s) indicates that the entry of mature dendritic
      cells into lymphatic vessels may not be as rigidly regulated by adhesion
      molecules as the process of extravasation from blood vessels.

PMID- 9561377
TI  - Positive blood cultures for coagulase-negative staphylococci in neonates: does
      highly selective vancomycin usage affect outcome?
AB  - The implication of highly-selective vancomycin usage on the outcome for infants
      with positive blood cultures for coagulase-negative staphylococci (CONS) was
      assessed retrospectively. The analysis was performed on partly prospective
      collected data from infants under 3 months of age with a least one CONS-positive
      blood culture in the neonatal intensive care unit at the Soroka University
      Medical Center between 1990 and 1996. During the study period, 239 episodes of
      CONS-positive blood cultures were identified from among 64,226 live births (3.7
      per 1,000). Vancomycin was administered in 22 (9%) episodes, in all cases only
      after identification of the bacteria. The remaining 217 episodes were managed
      either without antibiotics or with continuation or initiation of empiric
      antibiotic therapy (usually ceftazidime +/- ampicillin) for suspected sepsis.
      Severity of the initial illness, subsequent morbidity and mortality were low
      regardless of the treatment administered. Only a single case of a blood-borne
      vancomycin resistant gram-positive organism was observed during the study period.
      The approach to CONS-positive blood cultures in neonates used here was associated
      with low morbidity and mortality. These findings support a policy of highly
      selective vancomycin usage in an era of emerging vancomycin resistance.

PMID- 9561376
TI  - The significance of endotoxin release in experimental and clinical sepsis in
      surgical patients--evidence for antibiotic-induced endotoxin release?
AB  - Sepsis and peritonitis remain a serious challenge for surgical patients, despite
      improvement in surgical therapy and intensive care and the introduction of new
      powerful antibiotics. Recent in vitro studies revealed the potential of certain
      antibiotics, e.g. penicillin-binding protein (PBP) 3-specific antibiotics, to
      cause antibiotic-induced endotoxin release. Other types of antibiotics, e.g., PBP
      2-specific antibiotics, were associated with no or less endotoxin release.
      Further in vitro experiments and investigations in animals support the hypothesis
      of antibiotic-induced endotoxin release, but there is little clinical evidence.
      The clinical significance of endotoxin is subject of open dispute with many pro's
      and contra's. Endotoxin, although an important trigger, may not be the only
      factor to induce cytokine release, e.g., peptidoglycans were able to stimulate
      cells to release cytokines. Gram-positive pathogens have gained more importance
      in clinical sepsis and may not be sufficiently reflected in current clinical
      studies. The hypothesis that neutralization of endotoxin and pro-inflammatory
      cytokines is beneficial in sepsis was seriously challenged by the results of
      recent clinical and experimental studies. The better understanding of mechanisms
      in endotoxin-induced cell activation and cell, cell-receptor and soluble receptor
      interactions led to new treatment options. Recent reports on the complex
      pathogenesis of peritonitis and the detection of pathogen-related factors with
      intraperitoneal immune response may have implications on clinical studies
      investigating the potential of new compounds and the effect of antibiotics on
      endotoxin release. However, only few reports are available on the clinical
      significance of antibiotic-induced endotoxin release, and association of
      endotoxin release with pathogens, mortality or alteration of physiological
      parameters were not observed. With regard to the particulars of these studies,
      e.g., a small study population or low mortality rate, mortality may not be an
      ideal outcome parameter for these studies. There is clinical evidence for
      antibiotic-induced endotoxin release. However, the need for well-designed and
      performed studies using newly developed monitoring devices in intensive care
      therapy is obvious.

PMID- 9561378
TI  - Mediterranean leishmaniasis in HIV-infected patients: epidemiological, clinical,
      and diagnostic features of 22 cases.
AB  - Twenty-two Italian HIV-infected patients developed leishmaniasis, clinically
      manifested as visceral (13 cases), cutaneous (2 cases) and disseminated disease
      (7 cases). Twenty were males and two females (mean age: 32.8 years) with a mean
      CD4+ cell count of 46.8/microliter at diagnosis; risk factors were intravenous
      drug use (17 patients) and sexual behaviour (two bisexual, two homosexual, one
      heterosexual). All but one patient lived or travelled in hypoendemic Italian
      regions and other Mediterranean countries. Apart from the two patients with
      cutaneous leishmaniasis, the clinico-pathological and biological spectrum of the
      infection was often atypical, especially in patients with disseminated disease.
      The diagnosis was routinely made by direct recovery of parasites in biological
      specimens, mainly in bone marrow aspirate, whereas serology was negative or
      borderline in most of the patients. Among 17 in vitro isolates, Leishmania
      infantum was the only species involved with previously undescribed isoenzyme
      patterns in two cases. Treatment with antimonials and other drugs showed only
      temporary clinical improvement in some patients. Relapses were the rule.
      Leishmaniasis confirms itself as an opportunistic infection in HIV-positive
      persons. Secondary chemoprophylaxis should be considered in cases of relapsing
      disease.

PMID- 9561379
TI  - Correlation between plasma levels of cytokines and HIV-1 RNA copy number in HIV
      infected patients.
AB  - The plasma levels of HIV-1 RNA, tumor necrosis factor alpha (TNF-alpha), soluble
      receptors type II of TNF-alpha (sTNF-alpha RII), soluble receptors of interleukin
      4 (sR IL-4), interleukin-6 (IL-6), soluble receptors of interleukin-6 (sR IL-6),
      granulocyte macrophage colony stimulating factor (GM-CSF), soluble receptors of
      GM-CSF (sR GM-CSF), RANTES, MIP-1 alpha and MIP-1 beta were measured in 80 HIV
      infected patients. All patients had not been treated previously with
      antiretroviral drugs and did not present a recent history of opportunistic
      infection. A statistically significant correlation was found between HIV-1 RNA
      and TNF-alpha (p = 0.005) or sTNF-alpha RII levels (p < 0.001). RANTES and MIP-1
      alpha levels did not correlate with HIV-1 RNA. MIP-1 beta levels were correlated
      with plasma RNA titers in patients with CD4+ T cells < 200 x 10(6)/l (p = 0.03).
      MIP-1 alpha and sR IL-4 levels were significantly different according to the CD4+
      T cell range (p = 0.003 and p = 0.0002, respectively). GM-CSF and sR GM-CSF were
      undetectable in each case. These data confirm that HIV-1 replication in the
      plasma is correlated with TNF-alpha levels, but do not show a clear correlation
      with levels of the chemokines studied.

PMID- 9561380
TI  - Immune status against diphtheria among immigrants from the former USSR who
      arrived in Israel during 1990-1991.
AB  - Large outbreaks of diphtheria occurred recently in the former USSR. Between 1989
      and 1994, a total of about 600,000 Soviet immigrants arrived in Israel. The
      immune status against diphtheria in a sample of 992 men aged 17-49 and 195 women
      aged 17-19, who arrived in Israel during 1990-91, was studied in order to
      evaluate the need for vaccination. Participants completed a self-administered
      questionnaire and diphtheria antitoxin antibody levels were measured by means of
      ELISA. At age 17-19, the prevalence of antitoxin antibody levels below the
      protective level of 0.01 IU/ml was 4.8% in the men and 2.1% in the women. Among
      the men, the percentage lacking protection declined from 4.8% at age 17-19 years
      to 1.6% at age 20-24, and increased to 18.2% at age 35-49. In the oldest group,
      the prevalence of those lacking protection was considerably higher than for the
      general Israeli population. In the multivariate analysis, age, mother's education
      and republic of origin were significantly associated with the absence of
      protection. Immigrants from the former USSR appear to be more susceptible to
      diphtheria, thus increasing the possibility of clinical disease, and it is
      recommended that they receive booster doses of diphtheria toxoid.

PMID- 9561381
TI  - Imbalance in cytokine production by whole blood related to presence of
      cytopathogenic HIV-1 strains in HIV-1-infected patients.
AB  - The possible association between the emergence of cytopathogenic HIV-1 variants
      and disturbance of the cytokine production in the course of HIV-1 infection was
      studied in 18 infected patients. The cytopathogenicity of the isolates was
      studied in a microassay based on the use of HIV-1-infectible Hela-CD4 cells
      carrying the bacterial LacZ gene under the control of the HIV-LTR (P4 cells). In
      addition, the production of cytokines by heparinized whole blood (HWB) obtained
      the same day from HIV-1(+) patients was measured. TNF-alpha was determined in a
      one-step procedure combining HWB culture in the presence of LPS+PHA for 24 h and
      detection of cytokines in the same wells. In separate experiments HWB was
      cultured in the presence of LPS+PHA for 48 h, then the supernatants were
      collected and stored until assayed by ELISa for IFN-gamma and IL-4. Higher TNF
      alpha levels were found in activated HWB of patients with cytopathic strains (n =
      9) than in patients with non-cytopathic strains (n = 9, p = 0.02) assessed with
      P4 cells. A defective production of type 1 cytokine (IFN-gamma) and no increased
      secretion of type 2 cytokines (IL-4) was observed in patients with cytopathic
      strains. IFN-gamma/IL-4 ratios were significantly lower in patients with
      cytopathic strains (n = 9) than in other patients (n = 9, p = 0.009). The results
      show that the disarray of cytokine production, as assessed with whole blood
      culture, is associated with the cytopathogenicity of HIV-1 isolates in HIV-1
      infected individuals.

PMID- 9561382
TI  - Hepatitis G virus coinfection in chronic hepatitis B and C patients in Poland.
AB  - This study evaluated the epidemiology and impact of hepatitis G virus (HGV)
      infection in patients with chronic hepatitis B and C. Serum samples were obtained
      from 128 consecutive untreated patients with chronic hepatitis B (72 cases) or C
      (56 cases). The presence of HGV RNA was determined by PCR amplification of the
      5'untranslated region; the sensitivity of the assays was ten template copy
      equivalents. The prevalence of HGV RNA in hepatitis B and C was found to be 25%
      and 34%, respectively. HGV-positive and HGV-negative patients did not differ with
      respect to risk factors for infection, age, sex, or alanine aminotransferase
      activity. Similarly, there was no difference in the severity of liver disease, as
      assessed with HAI score. In conclusion, we found a very high prevalence of HGV
      infection in chronic hepatitis B and C patients in Poland. Nevertheless, no
      evidence was found that HGV coinfection has any impact on the severity of the
      underlying disease.

PMID- 9561383
TI  - IgA1 protease production by bacteria colonizing the upper respiratory tract.
AB  - Thirty-eight clinical isolates of Haemophilus influenzae and ten clinical
      isolates of Streptococcus pneumoniae were examined for IgA1 protease production.
      A suspension of surface material of each individual strain was incubated with
      human secretory IgA; IgA1 cleavage products were detected by SDS-PAGE and
      immunoblotting. The high incidence of IgA1 protease-positive strains (68.4% of
      the examined H. influenzae and 100% of the examined S. pneumoniae strains)
      confirms that IgA1 protease activity is a frequent characteristic of these two
      species. Yet the presence of this enzyme is, if at all, only a minor decisive
      factor for the induction of symptomatic infections of the upper respiratory tract
      by IgA1 protease-positive bacteria.

PMID- 9561385
TI  - Experimental genital tract infection with Chlamydia psittaci (GPIC agent) in male
      rats.
AB  - The course of experimental chlamydial infection of the male genital tract was
      studied. Inoculation of the Chlamydia psittaci agent of guinea pig inclusion
      conjunctivitis (GPIC agent) into the vas deferens of rats resulted in chlamydial
      infection of the epididymis, testis and the prostate gland. The inflammatory
      response was most prominent at 14 days after infection. Chlamydiae were recovered
      from the epididymides and the prostate glands for up to 90 and 60 days post
      inoculation, respectively. Histopathological changes associated with chlamydial
      infection of the epididymis or prostate gland were characterized by intratubular
      and interstitial purulent inflammation. Chlamydia-specific IgM- and IgG
      antibodies were found in sera of nearly all infected animals. Results of this
      study indicate that this animal model may be useful to study the pathogenesis,
      immune responses and sequelae of chlamydial infections of the male genital tract.

PMID- 9561386
TI  - Brucella-infected ovarian dermoid cyst causing initial treatment failure in a
      patient with acute brucellosis.
AB  - A 37-year-old woman was diagnosed with acute brucellosis. Despite appropriate
      antimicrobial therapy, high fever persisted. A contrast enhanced CT scan of the
      abdomen and pelvis revealed a left ovarian dermoid cyst. On the first
      postoperative day after left ovariectomy and right ovarian cystectomy were
      performed, the patient defervesced abruptly and continued to be completely
      afebrile. Cultures from bone marrow and dermoid cyst grew Brucella melitensis.
      The observation of a Brucella-infected ovarian dermoid cyst, which has not been
      previously reported, illustrates the importance of localized brucellosis as a
      cause of persistent infection despite appropriate antimicrobial therapy.

PMID- 9561387
TI  - Hepatitis A and B in persons with learning disabilities living in institutions:
      the need for vaccination.

PMID- 9561384
TI  - In vitro effect of cefodizime, imipenem/cilastatin and co-trimoxazole on
      dexamethasone and cyclosporin A depressed phagocytosis.
AB  - Phagocytosis is an important part of the host defense against infection.
      Antibiotics can influence phagocytic function. In the present study, leukocyte
      metabolic response to phagocytic challenge by latex was assessed in relation to
      in vitro addition of cotrimoxazole, imipenem/cilastatin, cefodizime,
      dexamethasone (DXM), and/or cyclosporin A (CsA). Using latex particles as
      phagocytic challenge, glucose-1-14C utilization and 14CO2 production were
      measured by liquid scintillation counting. The phagocytic response was impaired
      by in vitro addition of DXM or CsA and this setup was used as an experimental
      model of immunodepression. The addition of co-trimoxazole to control samples
      (without DXM or CsA) depressed the response to latex challenge, whereas imipenem
      and cefodizime had a neutral effect. In the presence of DXM, co-trimoxazole
      induced a further decrease. The depressive effect of DXM was partially
      neutralized in the presence of cefodizime. With CsA depression, co-trimoxazole
      also induced a further decrease, imipenem had a neutral effect, while cefodizime
      partially restored the CsA suppressed reaction. Co-trimoxazole depressed the
      phagocytic response, imipenem had a neutral effect, whereas cefodizime restored
      the experimentally induced immunosuppression.

PMID- 9561388
TI  - Prophylaxis of Pneumocystis carinii pneumonia in HIV-infected children one to
      five years old: a multicenter surveillance study in paediatric hospitals in
      Germany.

PMID- 9561389
TI  - Single-dose cefodizime as infection prophylaxis in abdominal surgery: a
      prospective multicenter study.
AB  - This prospective pilot study was performed to evaluate the efficacy, safety and
      tolerability of a single dose of cefodizime as infection prophylaxis in patients
      undergoing major abdominal surgery. One hundred forty-nine patients received 2g
      cefodizime, a third-generation cephalosporin, 30 min before abdominal surgery.
      The mean operation time was 116 +/- 66 min. Eighteen patients received
      metronidazole additionally. In 8/149 patients (5.4%) the final outcome was
      considered to be a treatment failure. 94.6% of the patients had no signs of
      infection. The long half-life of cefodizime allows a single-dose perioperative
      prophylaxis even in abdominal surgery lasting 3 to 4 h. Cefodizime can be
      regarded as a safe antibiotic prophylaxis with few side effects.

PMID- 9561390
TI  - Volatile organic compounds from the indoor mould Trichoderma viride cause
      histamine release from human bronchoalveolar cells.

PMID- 9561391
TI  - A regulatory role for carbon monoxide in mast cell function.

PMID- 9561392
TI  - Sick building syndrome: association of symptoms with serum IgE specific to fungi.

PMID- 9561393
TI  - Effects of permethrin on human basophils and lymphocytes in vitro.

PMID- 9561394
TI  - Current-voltage relationship in isolated mast cells during histamine liberation
      and membrane fluidisation.

PMID- 9561395
TI  - Ambroxol inhibits histamine release from human adenoidal mast cells.

PMID- 9561396
TI  - Effects of atrial natriuretic peptide, brain natriuretic peptide and urodilatin
      on histamine induced bronchoconstriction in the conscious guinea pig.

PMID- 9561397
TI  - Effects of prostanoid receptor agonists on immunologically-activated rat
      peritoneal mast cells.

PMID- 9561398
TI  - Effects of non-steroidal anti-inflammatory drugs and cyclooxygenase-2 specific
      inhibitors on mediator release from rat peritoneal mast cells.

PMID- 9561399
TI  - Role of phospholipase A2 and split lipid products in histamine release from mast
      cells.

PMID- 9561400
TI  - Tricyclic antidepressants change plasma histamine kinetics after its secretion
      induced by compound 48/80 in the rat.

PMID- 9561401
TI  - Imipramine inhibits histamine and serotonin secretion induced by various
      secretagogues.

PMID- 9561402
TI  - Motor behavioural function for histamine-dopamine interaction in brain.

PMID- 9561404
TI  - Histamine-induced synthesis and secretion of nerve growth factor from astrocytes.

PMID- 9561403
TI  - Increase of acetylcholine release from cortex of freely moving rats by
      administration of histamine into the nucleus basalis magnocellularis.

PMID- 9561405
TI  - Towards the optimal antihistamine: studies with ebastine.

PMID- 9561406
TI  - Mechanistic hypothesis concerning the unexpected suitable and undesirable effects
      of H1-antihistamines.

PMID- 9561408
TI  - Tiotidine, a classical H2-antagonist, presents characteristics of an inverse
      agonist in U937 cell line.

PMID- 9561407
TI  - Histamine receptors in human epithelial cells--characterization of the receptor G
      protein-effector system.

PMID- 9561409
TI  - Histamine synthesis by liver macrophages and its role in regeneration of the
      injured liver.

PMID- 9561410
TI  - Benzamidine-sensitive proteinase in activated cleavage of recombinant 74 kDa
      histidine decarboxylase into its 53 kDa form in mastocytoma cells.

PMID- 9561411
TI  - Induction of histidine decarboxylase in type 2 T helper lymphocytes treated with
      anti-CD3 antibody.

PMID- 9561412
TI  - Histamine receptors signalling in epidermal tumor cell lines with H-ras gene
      alterations.

PMID- 9561413
TI  - Day-to-day variation in urinary excretion of the histamine metabolite
      methylimidazoleacetic acid.

PMID- 9561414
TI  - The different effects of Helicobacter pylori strains on basal and histamine
      stimulated acid and pepsin production: an in vitro study.

PMID- 9561415
TI  - The relationship between mucosal histamine and fibrinolytic activity in duodenal
      ulcer disease.

PMID- 9561416
TI  - Identity of the diamine oxidase proteins in porcine kidney and intestine.

PMID- 9561417
TI  - Analysis of tissue and subcellular localization of mammalian diamine oxidase by
      confocal laser scanning fluorescence microscopy.

PMID- 9561418
TI  - Expression and cellular localisation of diamine oxidase in the gastrointestinal
      tract of pigs.

PMID- 9561419
TI  - Evidence for mast cell activation in collagenous colitis.

PMID- 9561420
TI  - Clinic modelling randomised trials (CMRT's) in animals as a new intermediate
      between biological experiments and randomised clinical trials: application to
      antihistamine prophylaxis in anaesthesia and surgery.

PMID- 9561421
TI  - Histamine release during rapid vancomycin administration.

PMID- 9561422
TI  - Causality-based diagnosis of histamine-related cardiorespiratory disturbances in
      surgical patients.

PMID- 9561424
TI  - Secular trends in the incidence of anorexia nervosa: integrative review of
      population-based studies.
AB  - OBJECTIVE AND METHOD: Aggregating across retrospective cohort samples, this
      integrative review synthesizes the findings of 12 cumulative incidence studies
      (45 hypotheses) on anorexia nervosa secular trends. RESULTS: (1) The female/male
      anorexia incidence rate ratio was estimated to be 8.20, 18.46 versus 2.25 cases
      per 100,000 per year, p < .05; (2) female teenagers experienced anorexia at a
      rate fivefold greater than other women, 50.82 versus 10.37 incident cases per
      100,000 per year, p < .001; (3) no secular trend or change in the incidence of
      anorexia was observed among teenagers, while a near threefold increase was
      observed over the past 40 years among women in their 20s and 30s, 6.28 (1950
      1964) versus 17.70 (1980-1992) cases per 100,000 per year, p < .05; and (4) the
      two cohort characteristics of age, and the age by year interaction accounted for
      nearly two thirds of the variability among anorexia incidence estimates, R2 =
      .614, F(2,27) = 21.49, p < .001. After the two factors of age and the Age x Year
      interaction were accounted for, none of the other study characteristics,
      including study year(s), were found to be significantly associated with anorexia
      incidence, that is, a main effect of time was not observed. DISCUSSION: The
      integrative evidence across the population-based epidemiologic studies covering
      40 years in this field suggests strongly that, overall, the incidence of anorexia
      nervosa, particularly among those very young women at greatest risk of
      experiencing it, has not increased significantly. However, the risk does seem to
      have increased significantly among women in their 20s and 30s.

PMID- 9561423
TI  - Can clinically relevant histamine release be accurately diagnosed in
      anaesthetised patients without plasma histamine measurements? Randomised study
      with nested sampling aimed to change paradigms.

PMID- 9561425
TI  - Food cravers: characteristics of those who binge.
AB  - OBJECTIVE: Food cravings are a frequently described antecedent to binge eating,
      yet not all of those who report food cravings also binge eat. The present study
      sought to determine the factors that distinguish cravers who binge versus those
      whose cravings are satisfied by a relatively "normal" amount of food. METHOD: A
      food craving questionnaire, a psychiatric diagnostic interview containing
      questions on binge eating, and a self-report booklet were completed by a group of
      cravers recruited by advertisement and a group of cravers from a randomly
      selected sample. RESULTS: In both groups, the cravers who binged were
      differentiated from those who did not binge by higher measures of body mass index
      (BMI), more frequent diagnoses of bulimia nervosa, a higher level of dietary
      restraint, and a by a temperament characterized by low self-directedness. In the
      recruited cravers, those who binged were also more likely to have had an episode
      of major depression, social phobia, to be cognitively controlled and harm
      avoidant. A comparison of recruited cravers with randomly selected cravers and
      control women suggests that greater rates of psychopathology and eating-related
      disturbances and lower levels of parental care may be found in recruited samples.
      DISCUSSION: In addition to elucidating factors associated with binge eating in
      cravers, this study highlights important differences between recruited and random
      samples.

PMID- 9561426
TI  - The initiation and the maintenance of dieting: structural models for large-scale
      longitudinal investigations.
AB  - OBJECTIVE: Female adolescents who engage in weight loss dieting often experience
      negative physical and psychological consequences. To reduce the occurrence of
      dieting, we need information about the factors associated with its initiation and
      maintenance. This paper outlines two separate structural models developed
      specifically for that purpose. METHOD: The theoretical rationale that informed
      the development of each of the models was derived from careful reviews of the
      literature on disordered eating, and from relevant psychological theoretical and
      empirical literature. RESULTS: Separate theoretical models are identified for the
      initiation of dieting, in which the core component is social influence, and for
      the maintenance of dieting, which assumes that differences in the persistence of
      dieting are best understood as motivational. Each model also incorporates
      individual differences and variables that are hypothesized to mediate the
      specific effects on dieting or to operate as moderators of the relationship.
      DISCUSSION: The operationalization of the components of the models and their
      application within large-scale longitudinal studies are discussed in relation to
      the need for systematic investigations of the way dieting begins and how it
      escalates or is maintained.

PMID- 9561427
TI  - The epidemiology of eating disorder behaviors: an Australian community-based
      survey.
AB  - OBJECTIVE: The study aims were to evaluate the prevalence and distribution of
      respective eating disorder behaviors (DSM-IV criteria) in a representative
      community-based sample. METHOD: Data were obtained from 3,001 interviews of a
      randomly selected sample of 4,200 individuals' (age > 15 years) households in
      South Australia. RESULTS: Ninety-six (3.2%) of respondents had regular current
      episodes of binge eating, 48 (1.6%) regularly fasted or used strict dieting, 24
      (0.8%) purged. An estimated 8 (0.3%) had bulimia nervosa and 30 (1%) had binge
      eating disorder. Binge eating and dieting were most common in people who were in
      their early to mid thirties. Dieting and purging, but not regular binge eating,
      were more common in women than in men. Purging was most common in the 35-44 year
      age range. The only behavior significantly associated with (increased) weight was
      binge eating. Unmarried subjects were less likely to diet than married subjects.
      No significant differences in rates of these behaviors were found for household
      income. DISCUSSION: Problematic eating disorder behaviors in older women and in
      men were more common than expected and merit further clinical and research
      attention.

PMID- 9561428
TI  - Patterns of interpersonal problems associated with binge eating disorder.
AB  - OBJECTIVE: To determine if interpersonal problems reported by individuals with
      binge eating disorder (BED) are distinct from psychiatric norms, and whether
      specific types of interpersonal problems are predictive of BED treatment outcome.
      METHOD: Subjects were 88 females with BED who completed a treatment trial for
      binge eating and weight loss. Pretreatment data on the Inventory of Interpersonal
      Problems (IIP) was compared (1) to that of psychiatric and nonpsychiatric norms
      and (2) for individuals with good versus poor outcome for eating disorder
      symptoms and weight loss. RESULTS: BED patients reported less distress for
      problems with being too vindictive (hostile dominance) than psychiatric norms.
      Patients with good eating disorder outcome reported less distress for problems
      with social avoidance; patients with good weight loss outcome reported greater
      distress over problems with vindictiveness. DISCUSSION: BED treatment may be
      enhanced by an initial focus on specific interpersonal difficulties.

PMID- 9561429
TI  - Variability in self-esteem, moods, shame, and guilt in women who binge.
AB  - Variability in self-esteem, moods, shame, and guilt was explored in a sample of
      78 women (37 who binge and 41 who do not binge) attending a large university.
      Results indicated that women who binge reported significantly greater
      fluctuations than women who do not binge in state self-esteem, negative affect,
      shame, and guilt. In addition, contrary to the hypotheses, self-esteem and
      positive affect increased prior to all eating episodes for women, including binge
      episodes for women who binge. Women who binge also reported lower levels of state
      self-esteem and positive affect, and higher levels of shame and guilt prior to
      binges than controls prior to their eating episodes. Theoretical implications of
      the differential role of shame and guilt are considered. In addition, results are
      discussed in terms of support for a self-nurturance explanation of binge eating
      in nonclinical samples of women.

PMID- 9561430
TI  - Personality disorders in patients with eating disorders in Japan.
AB  - We assessed the prevalence of personality disorders (PD) using the Structured
      Clinical Interview for DSM-III-R Personality Disorders (SCID-II) in 36 patients
      with restricting anorexia nervosa, 30 patients with anorexia nervosa and bulimia
      nervosa, and 42 patients with bulimia nervosa. Of the 108 patients, 51% met the
      criteria for at least one PD. The patients with PD had more severe clinical
      features in terms of bulimic behaviors, concurrent depressive, anxious, and
      obsessive-compulsive symptoms, and psychopathology related to eating disorders
      compared to the patients without any PD. The patients with PD, especially
      borderline PD, also had more severe global functioning and greater numbers of
      suicidal attempts and hospital admissions. We compare these results with those
      reported in the Western world and discuss them cross-culturally.

PMID- 9561431
TI  - An investigation of satiety in ageing, dementia, and hyperphagia.
AB  - OBJECTIVE: To investigate satiety in young, middle-aged, and elderly healthy
      adults, and in nonhyperphagic and hyperphagic elderly people with dementia.
      Previous work suggested hyperphagia in dementia was due to increased hunger and
      absence of satiation. METHODS: The primary measure of satiety was the amount of
      food eaten in an ad libitum meal, given 1 hr after a fixed preload. Three types
      of preload were used, high- and low-energy milkshakes and water. The effect of
      age was investigated by comparing the three groups of healthy adults. The effect
      of dementia was investigated by comparing the two demented groups with healthy
      elderly. RESULTS: Measurements suggested that accuracy of compensation for
      preload energy differences decreased with age and was absent in people with
      dementia. DISCUSSION: Lack of compensatory response in the elderly, particularly
      those with dementia, indicates the need for monitoring food intake to prevent
      over- or undereating.

PMID- 9561432
TI  - Emotional eating and eating psychopathology among non-eating-disordered women.
AB  - OBJECTIVE: A recent study (Arnow, Kenardy, & Agras, 1995, Journal of Behavioral
      Medicine, 15, 155-170) has reported on the development and preliminary validation
      of the Emotional Eating Scale (EES), a questionnaire measure of the tendency to
      eat in response to affective state. The EES showed high levels of validity among
      obese binge eaters, but there was no attempt to validate the measure among
      nonclinical groups. The present study assessed the validity of the EES among
      nonclinical women, in order to determine whether or not emotional eating is
      related to unhealthy eating characteristics among the general population.
      METHODS: The participants were 51 women with no current or past eating disorder.
      Each completed the EES and the Eating Disorders Inventory (EDI). Validity of the
      EES was tested using measures of internal consistency and correlations with EDI
      scales. RESULTS: The EES scales showed a high level of internal consistency and
      specific associations with EDI scales (particularly Bulimia, Ineffectiveness, and
      Interpersonal Distrust). The normative scores for this population were
      substantially lower than among binge eaters, but similar to those found among
      other clinical groups. CONCLUSIONS: The EES has good levels of validity. It
      demonstrates that emotional eating is related to bulimic eating attitudes in the
      broader population, although issues of causality need to be considered. The EES
      may have a role in the early identification of eating problems in nonclinical
      groups. Its utility with other eating-disordered groups remains to be
      established, but there are potential roles in the targeting and evaluation of
      treatment.

PMID- 9561433
TI  - Elevated total cholesterol in bulimia nervosa.
AB  - OBJECTIVE: It has been suggested that total serum cholesterol concentrations are
      elevated in bulimia nervosa. The objectives of this study were to compare
      cholesterol concentrations in women with bulimia nervosa with those of depressed
      women and population norms and to determine the dietary correlates of elevated
      cholesterol concentrations. METHODS: 126 women with bulimia nervosa and 57 women
      with major depression participating in clinical trials were studied. Total serum
      cholesterol concentrations were available for all participants. Prospective 2
      week dietary intake analysis was examined for 49 of the bulimic women. RESULTS:
      Bulimic women had markedly higher total cholesterol concentrations than depressed
      women and in comparison to consensus recommendations and population norms. This
      finding remained highly statistically significant after taking into account an
      array of potential physical and psychopathological covariates. Dietary analysis
      suggested that increased total cholesterol concentrations were related to
      cholesterol and fat intake during binge eating, but not during normal eating.
      DISCUSSION: Bulimic women have higher total cholesterol concentrations that are
      related to excess cholesterol and fat intake during binge eating.

PMID- 9561434
TI  - Smoking and bulimia nervosa.
AB  - OBJECTIVE: Little is known about the long-term physical consequences of bulimia
      nervosa. Some physical morbidity may result from high rates of cigarette smoking.
      The aim of the present study was to test three hypotheses regarding smoking among
      women with bulimia nervosa. METHOD: The subjects were 102 women with DSM-IV
      bulimia nervosa, 204 matched normal controls, and 102 matched controls with
      affective or anxiety disorders. All three groups were recruited from the same
      community sample. Interview measures were used for diagnosis and for information
      on smoking. RESULTS: A higher proportion of the bulimia nervosa cases were
      smokers than of either comparison group. Of those smokers who had achieved a
      period of abstinence, bulimia nervosa cases were more likely than normal control
      subjects to have resumed smoking, and more likely to attribute their resumption
      to concern about their weight. DISCUSSION: Smoking-related morbidity should be
      assessed in long-term follow-up studies of bulimia nervosa.

PMID- 9561435
TI  - Sociotropy, autonomy, and bulimic symptomatology.
AB  - OBJECTIVE: The cognitive-behavioral model of bulimia nervosa suggests that
      maladaptive cognitions are associated with the development and maintenance of
      bulimia nervosa. This study was conducted to evaluate (a) the relation between
      bulimic symptomatology and the cognitive-personality styles of sociotropy
      (reflecting themes of acceptance and approval) and autonomy (reflecting themes of
      independence and achievement), and (b) the specificity of the relation between
      these two cognitive-personality styles and bulimic versus depressive symptoms.
      METHOD: 105 undergraduate women were administered self-report measures of
      sociotropy and autonomy, as well as bulimic and depressive symptomatology.
      RESULTS: Whereas both sociotropy and autonomy were related to bulimic
      symptomatology, only sociotropy was uniquely associated with symptoms of bulimia
      when controlling for the effects of depressive symptoms. DISCUSSION: Themes of
      acceptance and approval may be important cognitive-personality features of
      bulimia nervosa.

PMID- 9561436
TI  - Perceptions of bed rest by anorexic patients.
AB  - OBJECTIVE: Few studies have investigated perceptions of operant conditioning
      programs by anorexic patients. This study examined patients' perceptions of the
      Bed Rest (BR) component which is employed in some operant conditioning programs.
      METHODS: A sample of 48 anorexic inpatients was administered a survey to elicit
      their attitudes towards BR. RESULTS: Results from the survey suggested that most
      patients perceived BR in a negative way. The main complaint, however, was not
      punishment or humiliation, as predicted, but isolation and boredom. A number of
      patients concluded that they wanted more individualization and distraction and
      less restriction while on BR. DISCUSSION: The findings justify the use of BR
      within a humane framework in the inpatient treatment of anorexia nervosa, but
      suggest that patients' perceptions of BR warrant systematic scrutiny.

PMID- 9561437
TI  - Secular changes in standards of bodily attractiveness in women: tests of a
      reproductive model.
AB  - OBJECTIVE: Since success at work is favored by a more slender body build while
      reproduction is favored by curvaceousness, standards of women's bodily
      attractiveness should be predictable from economic and reproductive variables.
      METHODS: This hypothesis was tested in a replication and extension of a study by
      Silverstein, Perdue, Peterson, Vogel, and Fantini (1986) which looked at
      correlates of curvaceousness of Vogue models over time. RESULTS: As economic
      prosperity increased, and as women's participation in the economy, and higher
      education, increased, curvaceousness of the standards declined. As the proportion
      of single women to men, both aged 20-24 years, increased, and as the birth rate
      declined, curvaceousness was reduced. DISCUSSION: Results suggest that cultural
      standards of attractiveness are influenced by an evolved psychology of mate
      selection.

PMID- 9561438
TI  - Reflections on prevention in dieting-induced disorders.
AB  - OBJECTIVE: The purpose of this article is to reflect on current approaches to the
      prevention of anorexia nervosa and bulimia nervosa. METHOD: The literature on
      preventing those disorders was examined within the context of the published
      literatures concerned with preventive interventions for adolescent drug-taking
      and alcohol-related behaviors. RESULTS: Our review revealed that those involved
      in preventing eating disorders maintain the traditional distinction between
      primary and secondary prevention, although the fruitfulness of that
      categorization is now uncertain. DISCUSSION: It is argued that interventions for
      dieting-induced disorders ought to be generic, and target the gamut of
      transitional risk behaviors among adolescents. Programs for dieting, cigarette
      smoking, alcohol use, and safe sex within the health and social development
      curricula in schools must be sustained by comprehensive efforts within the
      broader context of societal and systemic change.

PMID- 9561439
TI  - Plasma concentrations of leptin in a bulimic patient.
AB  - Recently, the obese gene in the ob/ob mouse was cloned, along with its human
      homologue. The gene product leptin is important in the regulation of body weight.
      Excessive food intake during a binge might affect leptin synthesis.
      Alternatively, fluctuations in leptin synthesis might induce binge eating.
      Therefore, plasma leptin levels of a patient with bulimia nervosa were determined
      over a period of 48 hr in a natural setting. Amount, type, time of food intake,
      and binging and purging episodes were concomitantly assessed. Although binging
      and purging episodes were quite frequent, leptin levels remained stable and were
      neither related to food intake nor to binge episodes.

PMID- 9561440
TI  - Seventh interscience world conference on inflammation, antirheumatic, analgesic
      immunomodulators, cardiovascular diseases and inflammation: WHO activities.

PMID- 9561441
TI  - Mechanism of action of antiinflammatory drugs.
AB  - In 1971, Vane showed that nonsteroid antiinflammatory drugs (NSAIDs) inhibited
      the biosynthesis of prostaglandins and proposed this as their mechanism of
      action. Much work around the world has followed. The aspirin-like drugs inhibit
      the binding of the prostaglandin substrate, arachidonic acid, to the active site
      of the enzyme. After characterization of the COX-1 enzyme in 1976, a second COX
      gene was discovered in 1991 encoding for the inducible COX-2. The constitutive
      isoform of COX, COX-1, has clear physiological functions. The inducible isoform,
      COX-2, is induced by pro-inflammatory stimuli in migratory cells and inflamed
      tissues. The range of activities of NSAIDs against COX-1 compared to COX-2
      explains the variations in the side effects of NSAIDs at their antiinflammatory
      doses. Drugs which have the highest potency on COX-2 and less effect on COX-1
      will have potent antiinflammatory activity with fewer side effects. All the
      results published so far support the hypothesis that the unwanted side effects of
      NSAIDs, such as damage to the gastric mucosa and kidneys, are due to their
      ability to inhibit COX-1, while their antiinflammatory (therapeutic effects) are
      due to inhibition of COX-2. Other roles for COX-2 inhibitors will surely be found
      in the next few years, for prostaglandin formation is under strong control in
      organs such as the kidney, lungs and uterus. COX-2 is also potently expressed in
      human colon cancer cells, and NSAIDs delay the progress of colon tumors possibly
      by causing apoptosis of the tumor cells. The risk of developing Alzheimer's
      disease, which may involve an inflammatory component, is lessened by chronic
      ingestion of NSAIDs. The new highly selective inhibitors of COX-2 will not only
      provide a means of delaying premature labor but will also lead to advances in
      cancer therapy and protection against Alzheimer's disease.

PMID- 9561442
TI  - Transcriptional regulation of fatty acid cyclooxygenases-1 and -2.
AB  - Transcriptional regulation of fatty acid cyclooxygenase isozymes (COX-1 and COX
      2) were studied using two cell lines. A rapid and transient induction of COX-2
      was observed by the addition of tumor necrosis factor alpha (TNF alpha) to murine
      osteoblastic cells MC3T3-E1. Possible involvement of NF kappa B and NF-IL6 as
      transcription factors was shown by deletion experiments using a luciferase
      reporter gene. COX-1 induction by a phorbol ester was demonstrated along with
      differentiation of human megakaryoblastic cells CMK to megakaryocytes.

PMID- 9561443
TI  - Stress and the hypothalamo-pituitary-immune axis.

PMID- 9561444
TI  - [Fibrogenesis. Pathophysiology and therapeutic approaches].

PMID- 9561446
TI  - [Diagnosis and therapy of ascites in liver cirrhosis].

PMID- 9561445
TI  - [Nutrition in liver cirrhosis].

PMID- 9561448
TI  - [Esophageal varices, hypertensive gastropathy. Diagnosis and therapy].

PMID- 9561447
TI  - [Spontaneous bacterial peritonitis].

PMID- 9561449
TI  - [Surgical therapy of portal hypertension].

PMID- 9561450
TI  - [Dysuria and urinary incontinence].

PMID- 9561451
TI  - [43-year-old patient with undulating fever of unknown origin and abdominal
      symptoms].

PMID- 9561452
TI  - [Unilateral giant extremity growth, naevus flammeus and chronic venous
      insufficiency in a 48-year-old patient].

PMID- 9561453
TI  - [Effects and risks of substituted amphetamines (Ecstasy)].

PMID- 9561454
TI  - [Lysis and central venous catheterization in myocardial infarct. Medical and
      legal problems].

PMID- 9561455
TI  - [Alternating dosage of bisoprolol?].

PMID- 9561456
TI  - [Intolerance reaction caused by biogenic amines. A separate disease entity?].

PMID- 9561457
TI  - [Cardiac tamponade in a 21-year-old body builder after abuse of anabolic drugs].

PMID- 9561458
TI  - [Diuretics in heart failure].

PMID- 9561459
TI  - Meeting the health care needs of adolescents in managed care. A position paper of
      the Society for Adolescent Medicine.

PMID- 9561460
TI  - Meeting the health care needs of adolescents in managed care: a background paper.

PMID- 9561461
TI  - Adolescents' knowledge of their health insurance coverage.
AB  - PURPOSE: To determine the accuracy of adolescents' self-report of health
      insurance coverage, using parents' report as a comparison standard. METHODS: Two
      separate samples of urban, school-based adolescents and their parents completed
      self-administered questionnaires about type of health insurance coverage. Sample
      1 included 123 and Sample 2 included 93 adolescent-parent pairs. Percent
      agreement and the kappa statistic were determined for each of the sample groups,
      and for males versus females and older (> 14 years) versus younger (< or = 14
      years) adolescents. RESULTS: In Sample 1, 33% of adolescent respondents responded
      "don't know" to the question about type of insurance coverage, and 4% left the
      question blank; in Sample 2, 3% answered "don't know," with none leaving the
      question blank. For Sample 1, we found a 57% rate of agreement of adolescents
      with their parents, and a corresponding kappa of .21. Females and older subjects
      demonstrated greater accuracy, with kappa's all in the range .13-.29. In Sample
      2, 73% of subjects agreed with parents' report, with a kappa of .48. Females and
      older subjects also demonstrated greater accuracy, with the highest kappa of .59
      demonstrated by older females. Excluding those responding with "don't know," we
      found overall percent agreement with parents of 87% in Sample 1 and 73% in Sample
      2; the corresponding kappas were .47 and .51. Females demonstrated higher
      agreement with parents in both samples. The results stratifying by age were
      inconsistent. In Sample 1, privately insured subjects were more accurate
      reporters than those either on medical assistance or uninsured. In Sample 2, no
      differences were seen by type of insurance. CONCLUSIONS: Many adolescents do not
      know their health insurance coverage status. However, for those who did claim to
      know, acceptable rates of accuracy using both percent agreement and the kappa
      statistic were demonstrated. Further research is needed to determine how
      information about insurance is communicated to adolescents and how this knowledge
      affects access to and use of health services.

PMID- 9561462
TI  - The REACH Project of the Adolescent Medicine HIV/AIDS Research Network: design,
      methods, and selected characteristics of participants.
AB  - PURPOSE: To describe the Reaching for Excellence in Adolescent Care and Health
      (REACH) Project of the Adolescent Medicine Human Immunodeficiency Virus/Acquired
      Immunodeficiency Syndrome (HIV/AIDS) Research Network, a unique collaborative
      effort to conceive and implement a research design intended to examine HIV
      pathogenesis, pubertal hormonal variation, and the effects of sexually
      transmitted disease comorbidity in HIV-infected youth to improve their health
      care. METHODS: This multidisciplinary team has drawn on basic science and
      clinical experience to produce a study design with relevant and feasible study
      aims and testable hypotheses. Particular attention has been paid to centralized
      training and quality control practices. Standardized measurements include direct
      and computer interviews, physical examination, laboratory analysis, and medical
      chart abstraction. The protocol has been approved by local institutional review
      boards. RESULTS: A highly standardized and quality control monitored protocol has
      been implemented at 16 sites throughout the United States collecting historical,
      observational, and laboratory data in a group of HIV-infected adolescents and HIV
      negative controls. Preliminary data collected on subjects are consistent with
      published reports of the sociodemographic and clinical characteristics of the HIV
      epidemic in sexually active youth, thus supporting the integrity of the protocol
      development process. The study population is, for the most part, in older
      adolescence, predominantly minority and female, and with publicly financed or no
      health insurance. CONCLUSIONS: The REACH Project is positioned to address
      questions about the clinical course, immunologic profile, and viral dynamics in
      HIV-positive youth, and thus is able to inform drug development and management
      strategies for this understudied population.

PMID- 9561463
TI  - Predictive model of weapon carrying among urban high school students: results and
      validation.
AB  - OBJECTIVES: The purpose of this study was to identify the behavioral,
      psychosocial, and demographic predictors of self-reported weapon carrying among
      secondary school students who attend urban public schools. METHODS: Self-reported
      weapon carrying was measured in a schoolwide anonymous health survey conducted in
      two demographically comparable high schools in 1992, in Boston, Massachusetts.
      Indicators of self-perception, depression, stressful life events, and adolescent
      risk behaviors of substance use and sexual behavior, along with self-reported
      weapon carrying, were measured. The students in both schools were racially
      heterogeneous, with the majority of about 80% from black or Hispanic backgrounds.
      A predictive model was developed using a forward stepwise logistic regression
      model in one inner-city high school, and tested in a second high school. RESULTS:
      Self-reported lifetime weapon carrying was 32% overall. The major predictors of
      weapon carrying among urban secondary school students are a combination of
      demographic, psychosocial, behavioral, and school-related factors. This analysis
      indicates consistency in eight markers predictive of weapon carrying: lower age,
      male gender, regular marijuana use, sexual experience, having witnessed a crime,
      having skipped school, suicidal ideation, and having hit or "beat up" someone.
      Race parental education, and family composition were not significant predictors.
      Significant predictors of weapon carrying were marijuana use and sexual
      experience, each of which was consistently high in both schools. CONCLUSIONS: The
      model-building and validation presented in this study provide empirical evidence
      for three important conclusions. First, weapon carrying is associated with
      multiple and interrelated factors which include demographic, psychosocial,
      behavioral, and school-related characteristics of high school-age adolescents.
      Second, students with more risk factors are more likely to carry a weapon,
      suggesting that the variables are independent markers. Third, this study
      identified marijuana use and being sexually experienced as both highly predictive
      of weapon carrying. Implications of this study for prevention point to the need
      for comprehensive multidisciplinary services in high school that include mental
      health counseling as well as health education efforts aimed at behavior change.

PMID- 9561464
TI  - Perceived virulence of germs from a liked versus disliked source: evidence of
      magical contagion.
AB  - PURPOSE: This research tested the hypothesis that adolescents perceive germs and
      resulting illness to be more virulent when contracted from a disliked source than
      from a liked source. METHODS: High school students rated their imagined illness
      from a disliked person and a friend. Independent judges rated students' drawings
      of germs from the disliked source and from the friend. RESULTS: Students imagined
      their illness as more serious when contracted from a disliked source, and judges
      rated the germs from a disliked source as angrier and more threatening.
      CONCLUSIONS: These results are discussed in terms of the role of "magical
      contagion" in reducing adolescents' perceived vulnerability to consequences of
      their risk-taking behavior.

PMID- 9561465
TI  - Silent dropouts in health surveys: are nonrespondent absent teenagers different
      from those who participate in school-based health surveys?
AB  - OBJECTIVE: To compare the health problems, needs and behavior of pupils absent
      from school with participants in the Swiss Multicenter Adolescent Survey on
      Health. METHODS: The present pupils' group (N = 3324; adolescents between 15 and
      20 years old, randomly selected from high schools and professional centers of
      French-speaking Switzerland) answered a self-administered anonymous
      questionnaire. The absent pupils group (N = 96) was questioned on the phone by
      means of a shorter but similar version of the questionnaire. RESULTS: The
      proportion of respondents reporting skin problems, weight concerns, sleep
      difficulties, headaches, stomach aches, as well as vision or dental problems was
      higher in the present pupils sample (p < 0.01). The percentages of teenagers
      reporting the need for help were higher in the present pupils sample than in the
      absent group: nutrition (21.8 vs. 9.4, p < 0.01) stress (44.2 vs. 31.3, p <
      0.05), depression (28.4 vs. 18.9, p < 0.05), sleep problems (21.3 vs. 12.1, p <
      0.05), sports (9.2 vs. 4.2, p < 0.05), and love life (31.5 vs. 14.5, p < 0.01).
      The rates of hospitalizations and injuries were lower among absent pupils (28.2
      vs. 40.1, p < 0.01). A higher proportion of absent students were sexually active
      (p < 0.05). They had a tendency to use tobacco, alcohol, and cannabis more
      frequently than did present pupils (p < 0.05). CONCLUSION: Within the Swiss
      context, nonparticipation owing to school absenteeism is probably related less to
      physical or chronic health problems that to lifestyles which predispose these
      students to truancy.

PMID- 9561466
TI  - Bibliography of journal articles (July to December 1996).

PMID- 9561467
TI  - Fungal infection in the intensive care unit.
AB  - Fungal infection in critically ill patients is an increasingly prevalent problem.
      Candida spp. cause the majority of these infections in ICU. They occur most
      commonly in patients with severe underlying illness, multiple courses of
      antibiotics and intravascular catheters. Clinical diagnosis is difficult due to
      nonspecific signs and the frequent occurrence of widespread superficial
      colonization with Candida spp. in ventilated patients. Most patients are
      diagnosed using inferential evidence of infection, such as persistent pyrexia
      despite antibiotics, raised serum C-reactive protein and the presence of
      individual risk factors. Amphotericin B and fluconazole are the most commonly
      used anti-fungals dependent on the identity of the fungus. Most of these
      infections are endogenous; however, a proportion may be caused via the hands of
      healthcare staff or contaminated medical equipment.

PMID- 9561468
TI  - Third International Conference on Sepsis in the ICU: Maastricht, 24-26 June,
      1997.

PMID- 9561469
TI  - Mycobacterium terrae: a potential surrogate for Mycobacterium tuberculosis in a
      standard disinfectant test.
AB  - The susceptibility of Mycobacterium tuberculosis and Mycobacterium avium
      intracellulare to the disinfections used for spillage and heat sensitive
      instruments has received much attention in recent years. The use of clinical
      isolates of M. tuberculosis and M. avium-intracellulare as test organisms is
      considered unsuitable for standard tests due to their hazardous nature (category
      3 pathogens and slow growth rates). This has led to much debate in standards
      committees on the selection and use of a possible surrogate which would be safer
      and more practical to use and yet mimic the susceptibility of clinical isolates.
      This study compared the susceptibility of one possible surrogate Mycobacterium
      terrae NCTC 10856, with that of clinical isolates of M. tuberculosis H37 Rv and
      M. avium-intracellulare using a quantitative suspension test. The instrument and
      environmental disinfectants tested were a chlorine-releasing agent, sodium
      dichloroisocyanyurate (NaDCC) at 1000 ppm and 10,000 ppm av. Cl, chlorine dioxide
      at 1100 ppm av. ClO2 (Tristel, HayMan MediChem), 0.35% peracetic acid (NuCidex,
      Johnson & Johnson), 70% industrial methylated spirit (IMS), 2% alkaline
      glutaraldehyde (Asep, Galen), 10% succine dialdehyde and formaldehyde mixture
      (Gigasept, Schulke and Mayr). Results showed that the clinical isolate of M.
      avium-intracellulare was the most resistant of the three test organisms. M.
      terrae, which is not a category 3 pathogen, was slightly more resistant than M.
      tuberculosis and this would appear to be a suitable surrogate for establishing
      tuberculocidal activity. However, with an increase in the clinical significance
      of M. avium-intracellulare, particularly in human immunodeficiency virus (HIV)
      and immunocompromised patients, a more resistant surrogate is required. In the
      absence of such a surrogate, testing with M. avium-intracellulare in a clinical
      laboratory equipped for handling category 3 pathogens is still advised to
      establish mycobactericidal activity.

PMID- 9561470
TI  - Community-acquired urinary tract infection in adults: a hospital viewpoint.
AB  - The clinical and epidemiologic spectrum of 175 cases of community-acquired
      urinary tract infection (UTI) were evaluated at a university hospital. Patients
      were grouped in five different categories of which complicated UTI was the most
      common (39%). Bacteraemia was detected in eight patients (18%) of this group and
      in five (12%) with acute uncomplicated pyelonephritis. A single organism was
      isolated in 166 cases (95%). The rate of Escherichia coli bacteriuria ranged from
      60% (asymptomatic bacteriuria) to 94% (uncomplicated cystitis). Of the 184
      isolates, 92% were susceptible to ciprofloxacin and significantly high rates of
      resistance were found for ampicillin, cefazolin, cefuroxime, and co-trimoxazole.
      Isolates causing uncomplicated UTI had significantly high rates of resistance to
      ampicillin, amoxycillin-clavulanate and co-trimoxazole and those causing
      complicated UTI, had significantly high rates of resistance to most oral
      antibiotics tested, except quinolones and nitrofurantoine. Community-acquired UTI
      requiring hospital evaluation occurs in a complex group of patients, and current
      patterns of antibiotic resistance make it difficult to suggest empiric oral
      treatments in this setting.

PMID- 9561471
TI  - Cohorting of infants with respiratory syncytial virus.
AB  - During two winter periods (1994-1995 and 1995-1996), nasopharyngeal aspirates
      were obtained from infants and young children with an acute respiratory illness,
      after initial assessment in an area with six cubicles which serves as an
      admissions unit. Aspirates were sent for rapid diagnostic testing. Respiratory
      syncytial virus (RSV) positive patients were cohorted into two six-bedded bays on
      the paediatric wards. Over the two successive winter periods studied, 347 RSV
      positive patients were assigned to the cohort. No nosocomial infections were
      identified during the first winter; in the second, two were identified. Cohorting
      at admission eased clinical management, with one area used for high-dependency
      care and cubicles being freed for children with other infectious diseases.
      Nosocomial infection was minimized.

PMID- 9561472
TI  - Random amplification of polymorphic DNA (RAPD), pulsed-field gel electrophoresis
      (PFGE) and phage-typing in the analysis of a hospital outbreak of Salmonella
      enteritidis.
AB  - Isolates of Salmonella Enteritidis from 81 patients from Herlev Hospital or from
      Copenhagen County were analysed by random amplification of polymorphic DNA
      (RAPD), pulsed-field gel electrophoresis (PFGE) and phage-typing. Fourteen
      polymorphic markers from five decamer primers unambiguously placed all isolates
      into six RAPD groups: 65 isolates of phagetype 6 (PFGE type I) were resolved into
      three RAPD groups constituting 86, 12, and 2%, respectively. A fourth RAPD group
      of 10 isolates was coincident with phage type 8 (PFGE type II) and two isolates,
      one phage-type 1, the other phage-type 4 (both PFGE type I) formed the fifth
      group. The sixth group of four isolates was not phage typeable and was PFGE type
      III. Forty outbreak-related isolates of phage-type 6 were resolved into three
      strains. No diversity of phage-type 6 was found among isolates unrelated to the
      outbreak. It is concluded that RAPD is useful as a tool in investigations of
      microbial outbreaks in its own right, or to supplement phage-typing and PFGE of
      Salmonella Enteritidis.

PMID- 9561473
TI  - Molecular markers for the investigation of Mycobacterium gordonae epidemics.
AB  - Mycobacterium gordonae was isolated as a light growth from bronchoalveolar
      aspirates from nine patients over 12 months. All patients were in one hospital,
      and had been bronchoscoped for suspected malignancy. None of the patients had
      symptoms or radiographic findings of mycobacterial infection. The isolates were
      characterized by biochemical tests and molecular hybridization. Random amplified
      polymorphic DNA analysis (RAPD) was used to test whether the strains had a common
      origin. All the isolates generated four to eight fragments, and almost all
      presented distinct RAPD patterns. Antimicrobial resistance patterns to six agents
      confirmed that the isolates were unrelated. Thus epidemiologically unrelated
      strains of M. gordonae can exist as contaminants in the same department over a
      relatively short time frame. RAPD analysis is easy to perform, gives rapid
      results, and can be used for epidemiological analysis of M. gordonae isolates.

PMID- 9561474
TI  - Comparison of three methods for the molecular typing of Singapore isolates of
      enterococci with high-level aminoglycoside resistances.
AB  - Enterococci are frequently isolated as nosocomial pathogens and have often
      acquired intrinsic drug resistances. Molecular typing techniques have been
      developed to assist in epidemological and infection control measures. This study
      investigates enterococci with high-level aminoglycoside resistance (HLAR) from
      the National University Hospital (NUH) of Singapore, and evaluates and compares
      three methods for typing: restriction enzyme analysis by conventional gel
      electrophoresis [restriction fragment length polymorphism (RFLP)], pulsed-field
      gel electrophoresis (PFGE), and polymerase chain reaction (PCR) using random
      amplified polymorphic DNA (RAPD). Fifty-two isolates of Enterococcus faecalis and
      13 isolates of Enterococcus faecium were used for the study. The numbers of
      patterns obtained for E. faecalis and E. faecium were 26 and 4, respectively by
      the RFLP method, and very similar discrimination was obtained by PFGE. RAPD PCR
      results were not reliably reproducible. A single pattern type by RFLP accounted
      for 16 of the E. faecalis isolates, suggesting hospital spread.

PMID- 9561475
TI  - Pathogenesis of ventilator-associated pneumonia: is the contribution of biofilm
      clinically significant?

PMID- 9561476
TI  - Lancets as a source of sharps injuries.

PMID- 9561477
TI  - Impact of hygienic measures on the development of methicillin resistance among
      staphylococci between 1991 and 1996 in a university hospital.

PMID- 9561478
TI  - Anti-cancer dividends from captopril and other inhibitors of angiogenesis.

PMID- 9561479
TI  - The use of iron in patients on chronic dialysis: mistake and misconceptions.
AB  - Anemia is the most common hematologic abnormality in patients with chronic renal
      failure. The reasons for anemia in chronic renal failure are many and include
      erythropoietin and iron deficiencies, inflammation, infection, aluminum toxicity,
      and hyperparathyroidism. Iron deficiency alone affects more than 50% of patients
      on dialysis, and the estimated iron loss for these patients is 1.5 to 3 grams per
      year. The use of erythropoietin has also uncovered iron deficiency in a multitude
      of patients. Iron and erythropoietin supplementation has often restored normal or
      near-normal levels of hematocrit in these patients and has therefore improved
      some of the symptoms classically connected with chronic renal failure, such as
      fatigue, cold intolerance, and mental sluggishness, among others. Resistance to
      erythropoietin is frequently observed in the maintenance care for dialysis
      patients, and the most common reason is iron deficiency. It is important to
      understand the physiology of renal anemia, erythropoiesis and iron metabolism in
      order to avoid mistakes and misconceptions in the management of iron in chronic
      dialysis patients. In this article, we review several mistakes, misconceptions,
      practices, and guidelines in iron supplementation therapy. We also review the
      physiology of anemia in renal disease and the importance of erythropoietin and
      iron in causing anemia and discuss recent Dialysis Outcomes Quality Initiative
      (DOQI) guidelines on the topic.

PMID- 9561480
TI  - Gene transfer and kidney disease.
AB  - There is little doubt that molecular biological intervention therapy has come of
      age and its potential is arousing tremendous excitement. A gene transfer
      technique, the HVJ-liposome method, is now applicable as a tool for the
      dissection of molecular aspects in the pathophysiology of renal diseases, and for
      gene therapy in experimental glomerulonephritis. Overexpressed transforming
      growth factor (TGF)-beta in the normal rat glomeruli, by gene transfer of TGF
      beta cDNA, leads to glomerulosclerosis. However, inhibition of the TGF-beta
      action by antisense oligonucleotides can suppress the development of the
      experimental glomerulonephritis. We investigated whether in vivo gene transfer of
      chimeric proteins, composed of the extracellular domain of TGF-beta type II
      receptor fused with IgC-Fc, suppresses experimental glomerulonephritis. The
      expression of TGF-beta in glomeruli was suppressed and so was the extracellular
      matrix expansion. Taken together with clinical observation of up-regulation of
      TGF-beta in various glomerulopathies, the dys-regulation of the TGF-beta is
      important in the development of glomerulosclerosis, and manipulation of this
      overexpression may prove a novel therapeutic approach for slowing the progression
      of the disease.

PMID- 9561481
TI  - Ureteral obstruction as a complication of renal transplantation: a review.
AB  - Ureteral obstruction in a renal allograft, due to a variety of etiologies, is
      both a challenging diagnostic and therapeutic disorder. Since ureteral
      obstruction in a renal transplant recipient usually presents as azotemia, it must
      also be distinguished from acute rejection. Although ultrasound is non-invasive
      and readily available, the most definitive diagnostic tool is percutaneous
      nephrostomy tube placement with antegrade nephrostogram. A variety of therapeutic
      approaches are available to treat ureteral obstruction in a renal allograft.
      These procedures can be open (e.g., repeat ureteroneocystotomy) or utilize an
      endourological approach (e.g., transluminal ureteral dilatation). From an
      experimental standpoint, recent data in rodent models of experimental
      hydronephrosis demonstrate similar pathobiologic events in both the obstructed
      kidney and an allograft undergoing the chronic rejection process. To this end,
      investigation needs to be conducted to assess whether partial, unrecognized
      ureteral obstruction in an allograft hastens the development of chronic
      rejection. This would further underscore the importance of ureteral obstruction
      as a cause for not only acute azotemia in an allograft, but also chronic
      deterioration in renal transplant function.

PMID- 9561482
TI  - Molecular genetics of polycystic kidney disease.
AB  - Polycystic kidney disease (PKD) is a major, multigene disorder that is
      characterized by the growth of large, fluid-filled cysts from the nephrons and
      collecting ducts of affected kidneys. At least three different genes are thought
      to give rise to the autosomal dominant (ADPKD) form of PKD. Two of the genes
      (PKD1 and PKD2) have now been isolated and sequenced, and based on their
      predicted structures are thought to encode proteins (polycystin-1 and polycystin
      2) that function together as part of a multi-component membrane-spanning complex
      involved in cell-cell or cell-matrix interactions. Most mutations identified in
      affected families appear to be inactivating for the PKD1 and PKD2 genes, and
      recent evidence has suggested that a two-hit mechanism, in which the normal PKD1
      allele is also inactivated, may be required for cyst growth. The large number of
      genes showing abnormal expression in cystic kidneys in humans and rodent models
      suggests that cellular processes associated with signal transduction,
      transcriptional regulation, and cell-cycle control are involved in cyst formation
      and that the cellular defect in PKD directly affects the regulation of epithelial
      differentiation.

PMID- 9561483
TI  - Familial membranous nephropathy.
AB  - Numerous HLA studies suggest that genetic factors play an important role in the
      development of membranous nephropathy (MN). We studied seven patients with
      idiopathic MN, from three unrelated families of Italian ancestry. Complement
      phenotype analysis and restriction fragment length polymorphism (RFLP) typing of
      HLA class II and of the switch region genes were done in family members. In the
      first family, the father, one son, and one daughter had MN; another daughter had
      clinical glomerulonephritis. The three members with MN shared one HLA haplotype
      carrying DR beta 11; in the two siblings with the disease, the second HLA
      haplotype carried the DR beta 3.2 allele. In families 2 and 3, two brothers had
      MN: in family 2, they differed in at least one haplotype; in family 3, they
      differed in both haplotypes. Only family 3 was informative with regard to the
      RFLP of the switch region genes: the two siblings were identical for both Ig
      heavy chain haplotypes. No clinical, laboratory or morphologic features
      consistent with a secondary form of the disease were found. Familial clustering
      of MN suggests a genetically transmitted mechanism.

PMID- 9561484
TI  - Acquired hemolytic anemia after minor ABO incompatible renal transplantation.
AB  - Passenger lymphocytes in grafted kidney have been reported to result in
      autoimmune hemolytic anemia (AIHA) in minor ABO incompatible transplants. We
      followed up 15 cases of minor ABO incompatible transplants for one year. Two
      patients developed severe but self-limited auto-immune hemolytic anemia within
      two weeks of renal transplantation. Both were blood group A and had received a
      kidney from a group O donor. Preoperative cross-match and antibody screen was
      negative; however subsequent to the hemolytic episode, group-specific blood was
      incompatible and patients were transfused with group O, cross-match compatible
      blood. Serological tests showed positive direct anti-globulin test (DAT) and anti
      A was eluted from both cases.

PMID- 9561485
TI  - Apoptosis in lupus SLE-N IV and non-lupus mesangiocapillary glomerulonephritis
      type I MCGN. I. A comparative study.
AB  - Apoptosis plays an important role in the recovery from glomerulonephritis.
      Moreover, aberrant apoptosis seems to contribute to lupus nephritis. This study
      compared the intensity of apoptosis in lupus and non-lupus mesangiocapillary
      glomerulonephritis. We used an in situ cell death detection kit, POD, which
      detects single cell apoptosis in formalin-fixed renal tissue. Our material
      comprised 13 renal biopsy specimens from patients with lupus mesangiocapillary
      glomerulonephritis (SLE-N IV), 11 renal tissues from patients with non-lupus
      mesangiocapillary type I glomerulonephritis (MCGN) and 8 normal kidney samples.
      We checked the correlations between intraglomerular apoptotic cells and the total
      number of intraglomerular cells, the relationship between tubulointerstitial
      apoptotic cells and the relative interstitial cortical volume. The population of
      intraglomerular apoptotic cells was lower in tissues from SLE-N IV patients than
      patients with MCGN. In MCGN the intensity of apoptosis in glomeruli correlated
      significantly with the number of total glomerular cells. Tubulointerstitial
      apoptotic cells were infrequent in the kidney samples from patients with SLE-N IV
      and in the normal kidney. In the renal interstitium and tubuli the number of
      apoptotic cells did not correlate with the relative interstitial cortical volume
      in kidney tissue in patients with MCGN. In the biopsies from patients with SLE-N
      IV there was an inverse correlation between tubulointerstitial apoptotic cells
      and the relative interstitial cortical volume, so a low number of apoptotic
      tubulointerstitial cells was associated with fibrosis in the renal interstitium.
      The results illustrate the differences in the intensity of apoptosis in lupus and
      non-lupus glomerulonephritis. The low number of apoptotic cells in renal tissue
      from patients with SLE-N IV suggests regulation of apoptosis may be altered in
      the mechanisms of glomerular and tubulointerstitial damage in lupus nephritis,
      although the reduced apoptosis may simply be due to smaller numbers of cells in
      fibrotic areas.

PMID- 9561486
TI  - A physiologically based pharmacokinetic model incorporating dispersion principles
      to describe solute distribution in the perfused rat hindlimb preparation.
AB  - A physiologically based pharmacokinetic model incorporating dispersion principles
      has been developed to describe outflow data from the isolated perfused rat
      hindlimb preparation, for the three reference markers 14C-sucrose, 14C-urea, and
      3H-water and three 14C-labeled 5-n-alkyl-5-ethyl barbiturates; the methyl, butyl,
      and nonyl homologues. Also 51Cr-RBC and 125I-albumin were studied. The model
      consists of four parallel components representing each of the tissues comprising
      the hindlimb: skeletal muscle, skin, bone, and adipose. Attempts to simplify the
      model by using the principle of tissue lumping were made by examining the tissue
      equilibration rate constant k tau for each of respective tissues for each
      compound. It was found that simplification was only possible in the case of 3H
      water data. The model took into account a possible shunting component in the skin
      tissue and incomplete mass but not volumetric recovery from the system. The
      dispersion model characterizes the relative spreading of solute on transit
      through a tissue bed by a dimension-less parameter DN. The estimated dispersion
      numbers (DN) obtained were in the region of 2.7-4.72, 8.39-15.54, 0.61-2.74, and
      6.02-14.0 for skeletal muscle, skin, bone, and adipose, respectively, and were
      independent of the compound studied. These values are much larger than the range
      reported in the literature for hepatic outflow data, DN = 0.2-0.5, and suggest a
      greater heterogeneity of vascular flow in the different component tissues of the
      rat hindlimb.

PMID- 9561487
TI  - Physiologically based pharmacokinetic modeling of a homologous series of
      barbiturates in the rat: a sensitivity analysis.
AB  - Sensitivity analysis studies the effects of the inherent variability and
      uncertainty in model parameters on the model outputs and may be a useful tool at
      all stages of the pharmacokinetic modeling process. The present study examined
      the sensitivity of a whole-body physiologically based pharmacokinetic (PBPK)
      model for the distribution kinetics of nine 5-n-alkyl-5-ethyl barbituric acids in
      arterial blood and 14 tissues (lung, liver, kidney, stomach, pancreas, spleen,
      gut, muscle, adipose, skin, bone, heart, brain, testes) after i.v. bolus
      administration to rats. The aims were to obtain new insights into the model used,
      to rank the model parameters involved according to their impact on the model
      outputs and to study the changes in the sensitivity induced by the increase in
      the lipophilicity of the homologues on ascending the series. Two approaches for
      sensitivity analysis have been implemented. The first, based on the Matrix
      Perturbation Theory, uses a sensitivity index defined as the normalized
      sensitivity of the 2-norm of the model compartmental matrix to perturbations in
      its entries. The second approach uses the traditional definition of the
      normalized sensitivity function as the relative change in a model state (a tissue
      concentration) corresponding to a relative change in a model parameter.
      Autosensitivity has been defined as sensitivity of a state to any of its
      parameters; cross-sensitivity as the sensitivity of a state to any other states'
      parameters. Using the two approaches, the sensitivity of representative tissue
      concentrations (lung, liver, kidney, stomach, gut, adipose, heart, and brain) to
      the following model parameters: tissue-to-unbound plasma partition coefficients,
      tissue blood flows, unbound renal and intrinsic hepatic clearance, permeability
      surface area product of the brain, have been analyzed. Both the tissues and the
      parameters were ranked according to their sensitivity and impact. The following
      general conclusions were drawn: (i) the overall sensitivity of the system to all
      parameters involved is small due to the weak connectivity of the system
      structure; (ii) the time course of both the auto- and cross-sensitivity functions
      for all tissues depends on the dynamics of the tissues themselves, e.g., the
      higher the perfusion of a tissue, the higher are both its cross-sensitivity to
      other tissues' parameters and the cross-sensitivities of other tissues to its
      parameters; and (iii) with a few exceptions, there is not a marked influence of
      the lipophilicity of the homologues on either the pattern or the values of the
      sensitivity functions. The estimates of the sensitivity and the subsequent tissue
      and parameter rankings may be extended to other drugs, sharing the same common
      structure of the whole body PBPK model, and having similar model parameters.
      Results show also that the computationally simple Matrix Perturbation Analysis
      should be used only when an initial idea about the sensitivity of a system is
      required. If comprehensive information regarding the sensitivity is needed, the
      numerically expensive Direct Sensitivity Analysis should be used.

PMID- 9561488
TI  - Organ clearance concepts: new perspectives on old principles.
AB  - The removal capacity of an eliminating organ by metabolism and/or excretion is
      often expressed as its clearance. Metabolic and excretory clearances are
      considered to be mutually independent, and the sum of these constitute the whole
      organ clearance. The influence of metabolism on estimates of the excretory
      clearance and vice versa was examined for the liver and kidney with
      physiologically based models. Mass transfer first-order rate equations describing
      transport and removal were derived. Upon inversion of the matrices originating
      from the coefficients of these equations, the area under the curve (AUC) and
      clearance (dose/AUC) were obtained with the liver or kidney as the eliminating
      organ. A more complex solution was found to exist for the kidney since glomerular
      filtration, secretion; reabsorption, and intrarenal metabolism were present. To
      ascertain the effect of excretion on estimates of the metabolic clearance as well
      as the effect of metabolism on estimates of the excretory clearance, intrinsic
      clearances for excretion or metabolism were set to zero. Clearance values were
      found to be altered when alternate pathways were present. Whereas excretory
      clearance estimates were consistently reduced in the presence of metabolism,
      metabolic clearance estimates were affected differentially by excretion and
      varied according to the site of metabolism. Excretion reduced metabolic clearance
      estimates when metabolism occurred intracellularly. If metabolism occurred
      intraluminally (e.g., on the renal brush border or luminal membrane), the
      metabolic clearance estimate could become higher since the substrate was made
      available to the enzymes following its excretion. As expected, these changes
      depended on the relative magnitudes of the intrinsic clearances for metabolism
      and excretion. The above theory was applied to the elimination of enalapril which
      is both metabolized and excreted by the perfused rat liver and kidney
      preparations. Data obtained in these studies were consistent with a set of
      published physiologic parameters denoting transfer and intrinsic clearances.
      Perturbations on clearance estimates were studied by setting the
      metabolic/excretory intrinsic clearance to zero, then to some finite value. In
      liver, the avid hepatocellular metabolism of enalapril reduced biliary clearance
      by 73%. For the kidney, the fractional excretion (FE or unbound excretory
      clearance/glomerular filtration rate) was decreased modestly (from 0.64 to 0.44)
      with intracellular esterolysis, whereas if metabolism had occurred
      intraluminally, FE would have been significantly decreased (from 1.8 to 0.45).
      Simulation results show clearly that clearance estimates are affected by the
      presence of alternate removal pathways, and question the well-established
      principle the metabolic and excretory clearance estimates are independent of each
      other.

PMID- 9561489
TI  - Similarity or discrepancy in pharmacokinetic parameter estimation between bolus
      and infusion studies.
AB  - A recent study by Heatherington and Rowland showing discrepancies in steady-state
      volume of distribution (Vss) estimation of two barbiturates between bolus and
      infusion studies in rat hindlimb preparations was reviewed. Their rationale is
      that increasing the duration of administration may increase the accessibility for
      tissue distribution and thus increase Vss for compounds showing slow tissue
      uptake. Such a dosing-duration-dependent distribution concept is, however,
      inconsistent with the principle in linear kinetics that the fate or disposition
      function of any drug molecules is independent of time of administration and
      presence of other molecules. When their well-designed bolus studies were
      reanalyzed by including extrapolated outflow data from the last sampling time to
      infinity, the Vss values for the two barbiturates were found to be very similar
      to those obtained by the infusion method. Our analysis seems to validate a
      theoretical concept that parameter estimation is independent of the duration of
      administration in linear kinetics. A potential complication of using the bolus
      method to study Vss is presented.

PMID- 9561490
TI  - Metabolite mean transit times in the liver as predicted by various models of
      hepatic elimination.
AB  - Predicted area under curve (AUC), mean transit time (MTT) and normalized variance
      (CV2) data have been compared for parent compound and generated metabolite
      following an impulse input into the liver. Models studied were the well-stirred
      (tank) model, tube model, a distributed tube model, dispersion model (Danckwerts
      and mixed boundary conditions) and tanks-in-series model. It is well known that
      discrimination between models for a parent solute is greatest when the parent
      solute is highly extracted by the liver. With the metabolite, greatest model
      differences for MTT and CV2 occur when parent solute is poorly extracted. In all
      cases the predictions of the distributed tube, dispersion, and tanks-in-series
      models are between the predictions of the tank and tube models. The dispersion
      model with mixed boundary conditions yields identical predictions to those for
      the distributed tube model (assuming an inverse gaussian distribution of tube
      transit times). The dispersion model with Danckwerts boundary conditions and the
      tanks-in series models give similar predictions to the dispersion (mixed boundary
      conditions) and the distributed tube. The normalized variance for parent compound
      is dependent upon hepatocyte permeability only within a distinct range of
      permeability values. This range is similar for each model but the order of
      magnitude predicted for normalized variance is model dependent. Only for a one
      compartment system is the MTT for generated metabolite equal to the sum of MTTs
      for the parent compound and preformed metabolite administered as parent.

PMID- 9561491
TI  - Sample size determination for repeated measurements in bioequivalence test.
AB  - When the measurement of outcome is unreliable or the cost of obtaining an
      additional subject is relatively high compared to the cost of obtaining an
      additional measurement from the same subject, it may be desirable to consider
      taking more than one measurement per subject to increase power or to minimize the
      cost in a clinical trial. When each subject in two comparison groups has a fixed
      number of repeated measurements, this paper develops an asymptotic procedure to
      calculate the number of subjects per group required to achieve a given power for
      an a-level bioequivalence test. Furthermore, Monte Carlo simulation is used to
      evaluate the accuracy of the approximate sample size calculation procedure and a
      brief discussion on how to determine the optimal number of repeated measurements
      is included.

PMID- 9561492
TI  - Comparison of ED, EID, and API criteria for the robust optimization of sampling
      times in pharmacokinetics.
AB  - Optimization of the sampling schedule can be used in pharmacokinetic (PK)
      experiments to increase the accuracy and the precision of parameter estimation or
      to reduce the number of samples required. Several optimization criteria that
      formally incorporate prior parameter uncertainty have been proposed earlier.
      These criteria consist in finding the sampling schedule that maximizes the
      expectation (over a given parameter distribution) of det F (ED-optimality) or
      Log(det F) (API-optimality), or minimizes the expectation of 1/det F (EID
      optimality), where F is the Fisher information matrix. The precision and the
      accuracy of parameter estimation after having fitted a PK model to a small number
      of optimal data points (determined according to D, ED, EID, and API criteria) or
      to a naive sampling schedule were compared in a Monte Carlo simulation study. A
      one-compartment model with first-order absorption rate (3 parameters) and a two
      compartment model with zero-order infusion rate (4 parameters) were considered.
      Data were simulated for 300 subjects with both structural models, combined with
      several residual error models (homoscedastic, heteroscedastic with constant or
      variable coefficient of variation). Interindividual variabilities in PK
      parameters ranged from 25-66%. ED-, EID-, and API-optimal sampling times were
      calculated using the software OSP-Fit. Three or five samples were allowed for
      parameter estimation by extended least-squares. Performances of each design
      criterion were evaluated in terms of mean prediction error, root mean squared
      error, and number of acceptable estimates (i.e., with a SE less than 30%).
      Compared to the D-optimal design, the EID and API designs reduced the bias and
      the imprecision of the estimation of the parameters having a large
      interindividual variability. Moreover, the API design resulted in some cases in a
      higher number of acceptable estimates.

PMID- 9561493
TI  - The effect of diminazene aceturate on cholinesterase activity in dogs with canine
      babesiosis.
AB  - A clinical trial was designed to evaluate the effects of diminazene aceturate and
      its stabiliser antipyrine on serum pseudocholinesterase (PChE) and red blood cell
      acetylcholinesterase (RBC AChE) in dogs with babesiosis. The trial was conducted
      on naturally occurring, uncomplicated cases of babesiosis (n = 20) that were
      randomly allocated to groups receiving a standard therapeutic dose of diminazene
      aceturate with antipyrine stabiliser (n = 10) or antipyrine alone (n = 10). Blood
      was drawn immediately before and every 15 minutes for 1 hour after treatment.
      Plasma PChE showed a 4% decrease between 0 and 60 min within the treatment group
      (p < 0.05). No statistically significant differences were found between the
      treatment and control groups at any of the time intervals for PChE. There was an
      increase in RBC AChE activity at 15 min in the treatment group (p < 0.05). No
      significant differences were found between the treatment and control groups at
      any time interval for RBC AChE. In view of the difference in PChE, samples from
      additional, new cases (n = 10) of canine babesiosis were collected to identify
      the affect of the drug over 12 hours. No significant depression was identified
      over this time interval. The results suggests that the underlying mechanism in
      producing side-effects, when they do occur, is unlikely to be through
      cholinesterase depression.

PMID- 9561494
TI  - The effect of dietary protein on reproduction in the mare. IV. Serum progestagen,
      FSH, LH and melatonin concentrations during the anovulatory, transitional and
      ovulatory periods in the non-pregnant mare.
AB  - The effect of total protein intake and protein quality on the serum
      concentrations of certain reproductive hormones during the anovulatory,
      transitional and ovulatory periods were studied in 36 Anglo-Arab mares. High
      quality protein stimulated FSH and LH production during the late transitional
      period. Serum progestagen and melatonin concentrations were unaffected by the
      quality of protein nutrition during the anovulatory period. Mares receiving high
      quality protein exhibited a 10-14-day cyclical pattern of FSH release
      approximately 4-6 weeks earlier than the mares fed the lower-quality protein
      diet, and also ovulated 3-4 weeks earlier than the mares on the lower-quality
      protein diet. Progesterone concentrations during the 1st oestrous cycle after the
      anovulatory period were unaffected by protein quality in the diet.

PMID- 9561495
TI  - The effect of high broiler litter diets as survival ration on the health of
      sheep.
AB  - The use of broiler litter as an emergency feed during droughts and other periods
      of feed shortages was evaluated in terms of its effect on the health of sheep.
      Pure broiler litter (i.e. excreta plus wood shavings), and litter mixed with 7.5
      or 15% molasses were fed for 83 days to 2-year-old wethers. The addition of
      molasses to the litter caused a significant increase (p < 0.01) in feed intake
      and final body mass. Various parameters such as plasma enzyme activity, plasma
      metabolite concentrations and urine mineral and purine excretion did not differ
      among treatments. Histological evaluation revealed no liver or kidney pathology.
      Mild myocardial pathology was observed in all 3 treatment groups. This seems to
      be related to the presence of the ionophore-based coccidiostat, narasin, which
      was present in the litter at a concentration of 10 mg/kg. It is suggested that
      these histological lesions are of little practical significance and would not
      affect the health of sheep being fed the broiler litter as a survival feed.

PMID- 9561496
TI  - An epizoological study of wastage in thoroughbred racehorses in Gauteng, South
      Africa.
AB  - Wastage is the term used to describe the phenomenon of the loss of racehorses
      from conception to adulthood due to death or injuries (i.e. they never reach a
      race-track), or the days lost by racehorses due to not training or being
      withdrawn from a race. This epizoological study was conducted to investigate
      wastage in Thoroughbred horses used for flat racing in the Gauteng Province of
      South Africa. Data from 6 racing stables were recorded from 1 March 1993 to 28
      February 1994. Each trainer completed a daily training record of the horses in
      his stable. This questionnaire included reasons why a horse failed to train on a
      specific day, or was withdrawn from a race. During the year, 8480 days (8.1%) of
      the 105,108 total potential training days were lost by horses in the stables
      investigated. Of the days lost, 72.1% were due to lameness, 8.6% to respiratory
      problems, and 19.3% to other causes. The lost training days for the individual
      trainers ranged from 5.4 to 12.6%. Of the 579 horses included in the study, 291
      horses (50.3%) lost one or more training days; 541 problems resulting in wastage
      were found in these 291 horses; 263 (48.6%) cases were due to lameness and 49
      (9.0%) were caused by coughing. The balance were caused by poor weather
      conditions (11.3%), vaccinations (7.2%), wounds (4.6%), abnormal haematology
      results (1.8%), inappetence (2.2%), nasal discharge (2.0%), epistaxis (1.8%),
      babesiosis (1.8%), miscellaneous other conditions (7.9%) and unknown causes
      (1.8%). An attempt was made to continue the study for a 2nd year but too few
      questionnaires were returned. However, it was evident that the percentage of lost
      training days (8.2%) was similar to that of the previous year. The training days
      lost due to lameness (66.9%) and respiratory problems (8.4%) were also similar to
      those of the previous year. From the findings of the present study, it was
      concluded that lameness and respiratory disorders were the major causes of
      wastage in Thoroughbred racehorses in Gauteng. Further research into these causes
      of wastage in racehorses is needed.

PMID- 9561497
TI  - The effect of activation of the lactoperoxidase system and souring on certain
      potential human pathogens in cows' milk.
AB  - Conventional methods of ensuring the safety and soundness of cows' milk for human
      consumption, such as pasteurisation, are not always practical in poor
      socioeconomic conditions or in rural communities that lack modern amenities.
      Activation of lactoperoxidase (LP) system and souring of milk were investigated
      as potential alternative methods to sustain the safety of milk by inhibiting
      certain microorganisms with known pathogenic potential. The activation of the LP
      system inhibited the growth of Staphylococcus aureus and Escherichia coli by the
      order of 2 log values. The inhibition of Brucella abortus was negligible. The
      replication of Coxiella burnetti in milk was not disturbed even after 17 h of LP
      system activation at 20 degrees C, but the outcome of the LP-system treatment on
      Mycobacterium bovis could not be determined as the conventional culturing
      technique used to grow this organism did not allow full recovery. Souring
      inhibited the growth of S. aureus and E. coli also by the order of 2 log values.
      From the results obtained in this investigation are concluded that the activation
      of the LP-system and souring can be used to inhibit the growth of S. aureus and
      E. coli in cows' milk, thereby increasing its safety.

PMID- 9561498
TI  - A survey of animal welfare needs in Soweto.
AB  - The diagnostic phase of an interactive research evaluation model was used in the
      investigation of the animal welfare needs of a low-income urban community in
      South Africa. Data were gathered by means of a structured interview and direct
      observations by animal welfare officers. During the survey of 871 animal owners
      in Soweto, it was found that dogs were owned by 778 households and cats by 88
      households. The dog to human ratio was estimated at 1:12.4. Respondents were
      asked whether they enjoyed owning animals and 96.1% said that they did. Only
      26.3% mentioned that they had problems with their own animals and 16.6% had
      problems with other people's animals. Treatment of sick animals (29.7%) was seen
      as a priority. However, less than 1% (n = 6) used the services of private
      veterinarians. Others took their animals to welfare organisations or did not have
      them treated. Perceptions of affordable costs of veterinary treatments were also
      recorded. In addition to treatment, respondents indicated a need for vaccination
      (22.5%), sterilisation (16.5%), control of internal (3.7%) and external (8.8%)
      parasites, education and extension (6.6%), prevention of cruelty to animals
      (3.2%) and expansion of veterinary clinics to other parts of Soweto (1.3%).

PMID- 9561499
TI  - A survey of anthelmintic resistance on ten sheep farms in Mashonaland East
      Province, Zimbabwe.
AB  - A survey to detect anthelmintic resistance in nematode parasites of sheep was
      conducted on 10 randomly-distributed farms in the Chivhu District, Mashonaland
      East Province, Zimbabwe. Before the survey, a questionnaire was circulated to the
      farmers concerning nematode parasite control. Results showed that parasite
      control using anthelmintic treatment was the only method practised and that the
      benzimidazoles were the most frequently used anthelmintic drugs. The faecal egg
      count reduction test was used to detect resistance. The anthelmintic groups
      tested were benzimidazoles, levamisole and ivermectin. Resistance to
      benzimidazoles was detected on 6 of 10 farms and levamisole resistance on 2 of 3
      farms. Ivermectin resistance was not observed on the farms surveyed. Post
      treatment larval cultures indicated that Haemonchus contortus survived
      administration of fenbendazole, albendazole, oxfendazole and levamisole. A
      Cooperia sp. strain resistant to albendazole was detected and this is the first
      report in Zimbabwe of a resistant parasite in this genus.

PMID- 9561500
TI  - Right atrial myxosarcoma in a dog.
AB  - A case of right atrial myxosarcoma is described in a Staffordshire bull terrier
      with a history of weight loss, exercise intolerance and collapse. The diagnosis
      of an intracavitary cardiac tumour was made on echocardiography. The dog was
      euthanased. Secondary spread to the lungs and lymph nodes was present. Myxoma is
      one of the rare intracavitary cardiac tumours and this case is believed to be the
      1st report of its more malignant form in the dog.

PMID- 9561501
TI  - Chronic episodic diarrhoea associated with apparent intestinal colonisation by
      the yeasts Saccharomyces cerevisiae and Candida famata in a German shepherd dog.
AB  - A 3-year-old German shepherd dog was presented with a history of lifelong
      episodic diarrhoea. An adverse reaction to food was considered the most likely
      cause of the diarrhoea. The dog had received prolonged antibiotic therapy for
      most of its life as well as receiving probiotics containing the yeast
      Saccharomyces cerevisiae (syn. S. boulardi) for a year before referral. The
      probiotic was discontinued 2 months before to referral. Examination and culture
      of faecal samples identified yeast-like organisms, S. cerevisiae and Candida
      famata. S. cerevisiae has been isolated from humans in association with
      predisposing conditions such as prolonged sojourns in hospital,
      immunosuppression, broad-spectrum antibiotic therapy and prosthetic devices, but
      is regarded as non-pathogenic in humans and is rarely associated with disease in
      animals. C. famata has been isolated from animals, humans and the environment,
      but is regarded as a very rare pathogen. No evidence of immunosuppression was
      found in the dog. The presence of yeasts in the faecal isolates and the history
      of prolonged use of antibiotics and probiotics with a concurrent adverse reaction
      to food, suggest that conditions may have occurred within the bowel that made it
      possible for the yeasts to colonise parts of it. This has apparently not been
      reported before.

PMID- 9561502
TI  - Uterine horn aplasia with complications in two mixed-breed bitches.
AB  - Unilateral segmental uterine horn aplasia was found in 2 mixed-breed bitches. The
      1st bitch was presented with clinical signs of acute abdominal pain, and pyometra
      was suspected. Pyometra was confirmed surgically with rupture of a blind-ending
      cranial portion of the anomalous right uterine horn, which had resulted in
      peritonitis. The 2nd bitch was presented for routine ovariohysterectomy. The
      right uterine horn was affected by segmental aplasia, with mucometra of the
      cranial portion of the affected horn. Histopathology demonstrated both uteri to
      have diffuse cystic endometrial hyperplasia. It is postulated that cystic
      endometrial hyperplasia, together with the congenital anomaly, resulted in
      pyometra in one case and in mucometra in the other case. This is believed to be
      the 1st report of uterine horn aplasia in the bitch in association with clinical
      signs and lesions other than infertility.

PMID- 9561503
TI  - Suspected poisoning of puppies by the mushroom Amanita pantherina.
AB  - Amanita pantherina poisoning is suspected as the cause of a severe, transient
      neurological disorder in three 5-week-old German shepherd puppies. There was very
      strong circumstantial evidence that this mushroom had been eaten, and the signs
      encountered were similar to those described in confirmed field cases of
      intoxication in dogs. It was also in many respects consistent with the syndrome
      seen in humans. A veterinary perspective on the hallucinogenic Amanita spp. is
      given and the veterinary literature on mushroom intoxication is briefly reviewed
      as, in contrast to humans, it is not often reported in animals. This is the 1st
      report of suspected mushroom intoxication of animals in South Africa.

PMID- 9561504
TI  - Veterinary physiology and community development: are they compatible in a new
      South Africa?

PMID- 9561505
TI  - Lymphology around the world: taking stock of our achievements as we approach the
      21st century.

PMID- 9561506
TI  - Role of protein kinase C in the regulation of pumping activity in bovine
      mesenteric lymphatic vessels.
AB  - We investigated the role of protein kinase C (PKC) in regulating the lymphatic
      myogenic response. Bovine mesenteric lymphatics were suspended in an organ bath
      with inflow and outflow ends cannulated. Input was provided from a reservoir
      filled with Krebs solution. The PKC activator phorbol 12-myristate 13-acetate
      (PMA) inhibited pumping significantly whether tested at a fixed pressure or as
      pressures were raised in 2 cm H2O increments (50% inhibition achieved at 4.6 x
      10(-8)M. The inactive phorbol ester (4-alpha-PMA) had no effect. The specific PKC
      inhibitors calphostin (10(-9) to 10(-7)M) or chelerythrine (10(-8) to 10(-6)M)
      had no significant effect on pumping. However, chelerythrine (10(-6)M) was
      capable of reversing the inhibitory effects of PMA (5 x 10(-8)M). PKC activation
      is believed to inhibit nitric oxide (NO) production in some blood vessels, and
      previous work from our laboratory has demonstrated that NO is important in
      facilitating pumping activity in bovine lymphatics. We observed that sodium
      nitroprusside (sNP, 10(-7)M) or L-arginine (10(-4)M), reversed the depressor
      effects of PMA. These results suggest that PKC may not be involved in regulating
      the vessel's contractile response to pressure-induced stretch. However, the data
      with PMA suggest that these ducts contain PKC. PKC activation depresses lymphatic
      pumping and this effect may be mediated in part, by inhibition of NO.

PMID- 9561507
TI  - The risk of genital edema after external pump compression for lower limb
      lymphedema.
AB  - In a single lymphedema treatment facility, 128 consecutive patients with lower
      limb lymphedema were retrospectively analyzed for the development of genital
      edema. The patients were separated for analysis on the basis of who used or did
      not use compressive pump therapy. Of the 128 patients with lower limb lymphedema,
      75 received no pump therapy, and 53 used pumps. Of the 75 who did not use pump
      compression, only 2 had genital edema. Of the 53 patients who used pump
      compression, 23 patients developed genital edema after pump therapy (p < .0001).
      The incidence of genital edema was unaffected by age, sex, grade or duration of
      lymphedema, whether lymphedema was primary or secondary, whether a single or
      sequential pump was used, the pressure level applied, or duration or hours per
      day of pump therapy. Compressive pump therapy for lower limb lymphedema produces
      an unacceptably high incidence of genital edema.

PMID- 9561508
TI  - Inhibition of mitosis in the guinea pig thymus after ligation of draining
      efferent lymphatics.
AB  - Ligature of the cervical lymph duct in guinea pigs resulted in marked dilatation
      of the lymphatics draining the thymus and marked reduction of mitosis in the
      thymus. A decrease of about 50% in the number of mitoses was found in the cortex
      within one day after ligation and in the medulla within five days after ligation.
      The thickness of the cortex also decreased rapidly and markedly in direct
      proportion to the decrease in cortical mitosis. Mitosis in the thymus recovered
      within 10 days after ligation, presumably after regeneration of lymphatics or
      collateralization. Thickening of the walls and valves of the efferent lymphatics
      of the thymus after lymph congestion was also demonstrated.

PMID- 9561509
TI  - A forgotten woman professor and lymphologist.

PMID- 9561510
TI  - The lymphatic drainage of the left ventricle in the Yucatan minipig.
AB  - The gross anatomy of the cardiac lymphatic system draining the left ventricle was
      studied in 15 Yucatan minipigs and 2 regular swine. The findings confirm that the
      drainage pathways are similar to those of man and dog. After a coloring marker is
      injected near the apex of the left ventricle, one or more lymphatics are seen to
      ascend towards the left atrial appendage. Where there is more than one ascending
      lymphatic, they typically join before or at the left atrial appendage. This
      principal lymphatic then passes beneath the appendage and travels behind (dorsal
      to) the pulmonary artery and aorta to the right side of the mediastinum. From
      here, the lymphatic passes cephalad along the left border of the superior vena
      cava to enter the cardiac lymph node between the superior vena cava and the
      trachea.

PMID- 9561511
TI  - Magnetic resonance imaging of peripheral lymphedema.

PMID- 9561512
TI  - Lingering thoughts on three lymphateers.

PMID- 9561513
TI  - Diseases caused by voltage-gated ion channels.
AB  - Ion channels regulate the transfer of ions between the outer and the inner
      surface of the cell membrane. The opening of ion channels may be triggered by the
      binding of a ligand or variations in the membrane potential. Voltage-gated ion
      channels are an important class of such channels, that are involved in the
      generation and propagation of action potentials and play a key role in cell to
      cell communication. As a consequence of cloning and sequencing of ion channel
      genes, their role in diseases affecting excitable tissues such as the nervous
      system, heart and skeletal muscle has been examined, and a new class of diseases
      has emerged. We will review disorders caused by mutations in voltage-gated ion
      channels affecting these excitable tissues as well as non-excitable tissues such
      as the kidney. The clinician should be aware of this new class of diseases
      because pharmacological agents modulating channel functions are available.
      Characterization of these gene defects should lead to better treatment of these
      disorders.

PMID- 9561514
TI  - Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type
      and vascular dementia with deep white matter changes.
AB  - Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2),
      oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were
      investigated using positron emission tomography (PET) in 16 patients with senile
      dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and
      3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI
      and 6 controls. rCBF, rCMRO2 and rCBV were determined using C15O2, 15O2 and C15O,
      respectively. rCBF and CMRO2 were significantly decreased in the frontal,
      parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a
      significant correlation with the severity of dementia (P < 0.05). In patients
      with DWMH rCBF was significantly decreased in the parietal cortex and in the
      frontal white matter in nondemented patients, and in the cerebral cortex and
      white matter of most regions studied in demented patients (P < 0.05), whereas
      rCMRO2 was significantly reduced in only the frontal and temporal cortex of
      demented patients (P < 0.05). rOEF was significantly increased in the parietal
      cortex of patients with SDAT and in the white matter of patients with SDAT or
      DWMH (P < 0.05), and the increase in the frontal white matter significantly
      paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was
      significantly decreased in the parietal and temporal cortex of patients with SDAT
      (P < 0.05), but not in any areas of those with DWMH. These results suggest that
      rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in
      patients with SDAT may be accounted for by reduction in rCBV resulting from
      decreased activity in the vasodilatory cholinergic system, impairment of glucose
      metabolism and white matter changes; the rOEF increase in patients with DWMH
      suggests relative preservation of oxidative metabolism compared to disturbed
      perfusion.

PMID- 9561515
TI  - Volumetric MRI of the limbic system: anatomic determinants.
AB  - The limbic system comprises the hippocampal formation, fornix, mamillary bodies,
      thalamus, and other integrated structures. It is involved in complex functions
      including memory and emotion and in diseases such as temporal lobe epilepsy.
      Volume measurements of the amygdala and hippocampus have been used reliably to
      study patients with temporal lobe epilepsy but have not extended to other limbic
      structures. We performed volume measurements of hippocampus, amygdala, fornix and
      mamillary bodies in healthy individuals. Measurements of the amygdala,
      hippocampus, fornix and mamillary bodies revealed significant differences in
      volume between right and left sides (P < 0.001). The intraclass coefficient of
      variation for measurements was high for all structures except the mamillary
      bodies. Qualitative image assessment of the same structures revealed no
      asymmetries between the hemispheres. This technique can be applied to the study
      of disorders affecting the limbic system.

PMID- 9561516
TI  - Hepatic cirrhosis: magnetisation transfer contrast in the globus pallidus.
AB  - The magnetisation transfer ratio (MTR), a quantitative tissue characteristic, and
      the pallidal index were measured in the globus pallidus of 37 patients with
      hepatic cirrhosis and 37 control subjects. The MTR decreased with severity of the
      disease, as indicated by the serum total bililubin, indocyanine green 15-min
      retention rate, and plasma ammonia. The pallidal index correlated significantly
      with haematological parameters, although the correlation coefficients tended to
      be lower than those between MTR and haematological parameters. This change in MTR
      corresponded to the results of the manganese chloride experiments. T1 shortening
      in the pallidum of patients with cirrhosis is presumably caused by paramagnetic
      effects, and possibly attributed to manganese deposition.

PMID- 9561517
TI  - Radiological assessment of necrosis in glioblastoma: variability and prognostic
      value.
AB  - In a previous study, we found that the extent of necrosis was the only
      radiological feature which correlated significantly with survival in patients
      with glioblastoma. The aim of this paper was to evaluate the variability and
      prognostic value of the extent of the necrotic area as seen on contrast-enhanced
      MRI and CT in a larger series. We studied 72 patients who underwent surgical
      removal of supratentorial glioblastomas and had CT and/or MRI with contrast
      medium before surgery; 38, all undergoing the same treatment (surgery plus
      radiotherapy), were followed clinically. Necrosis within the tumour varied
      greatly, ranging from none (only 1 case) to involvement of 76% of the tumour.
      Survival data in the subgroup suggested that only patients with a small area of
      necrosis (less than 35% of the tumour) had a significantly longer survival time.
      When necrosis involved more than 35% of the mass, patients had a shorter survival
      time, without any further correlation with the extent of necrosis.

PMID- 9561518
TI  - Intracranial gas on CT after cardiopulmonary resuscitation: 4 cases.
AB  - We report four patients in whom gas was seen in the head on CT shortly after
      cardiopulmonary resuscitation. The gas was in the posterior cranial fossa,
      presumably within veins, or in the cavernous sinus. The cause of the cardiac
      arrest was myocardial infarction in three patients and hanging in one. All had
      peripheral or central venous lines. The mechanism by which gas appeared in the
      intracranial veins is discussed.

PMID- 9561519
TI  - Necrosis and haemorrhage of the putamen in methanol poisoning shown on MRI.
AB  - Methanol, a highly toxic substance, is used as an industrial solvent and in
      automobile antifreeze. Acute methanol poisoning produces severe metabolic
      acidosis and serious neurologic sequelae. We describe a 50-year-old woman with
      accidental methanol intoxication who was in a vegetative state. MRI showed
      haemorrhagic necrosis of the putamina and oedema in the deep white matter.

PMID- 9561520
TI  - Langerhans cell histiocytosis with involvement of the pons: case report.
AB  - Central nervous system involvement is uncommon in Langerhans cell histiocytosis.
      The suprasellar region is more frequently affected. There have been few reports
      of involvement of the brain parenchyma shown on CT or MRI. We present a case of
      involvement of the pons, showing marked contrast enhancement on MRI.

PMID- 9561521
TI  - Sonographic detection of haemodynamic changes in a case of vertebrobasilar
      insufficiency.
AB  - We present a diagnostically challenging case of vertebrobasilar insufficiency
      caused by head rotation. The patient was a 58-year-old man complaining of
      dizziness and faintness with head rotation to the left. Vertebral arteriography
      with the head turned to the left revealed mechanical compression of the right
      vertebral artery at the occipitoatlantal joints and an occluded left vertebral
      artery. Duplex sonography demonstrated disappearance of the end-diastolic flow
      signal in the right vertebral artery on head rotation, paralleling the appearance
      of symptoms. Decompression of the vertebral artery by transversectomy of the
      atlas and hemilaminectomy of the axis completely relieved the symptoms and the
      Doppler flow signal pattern of the vertebral artery returned to normal: End
      diastolic flow in the right vertebral artery did not disappear even when the head
      was rotated to the left.

PMID- 9561523
TI  - MRI-neuropathological correlations in type 1 lissencephaly.
AB  - Although imperfect, MRI is the best way of distinguishing type 1 lissencephaly
      from other, less classical lissencephalic malformations. We reported a case in
      which correlation of MRI and neuropathology was possible. Besides the classical
      radiological features of lissencephaly, i.e., agyria and excessive thickness of
      the cortex, an additional sign was observed: a thin cortical band, which gave
      high signal on T2-weighted images, represented a paucicellular and partially
      myelinated band, 1500 microns thick, lying under the true superficial cortex.
      This MRI feature could be characteristic of the particular cortical lamination
      observed in true type 1 lissencephaly.

PMID- 9561522
TI  - MRI of enlarged endolymphatic sacs in the large vestibular aqueduct syndrome.
AB  - We studied ten inner ears of five patients with a bilateral large vestibular
      aqueduct syndrome, using CT and MRI. Although the large vestibular aqueduct
      varied in size, a markedly dilated endolymphatic sac extending to the sigmoid
      sinus was demonstrated bilaterally on MRI in all patients. The cause of hearing
      loss in this syndrome is unclear. However, it is suggested that reflux of the
      protein-rich, hyperosmolar endolymph from the enlarged endolymphatic sac (EES)
      into the cochlea through a widely patent endolymphatic duct may damage the
      neuroepithelium. CT density and spin-echo MRI signal intensity of the endolymph
      in EES were markedly higher than those of CSF in eight inner ears of four
      patients. Increased density and high signal may indicate protein-rich,
      hyperosmolar endolymph. In some patients with sensorineural hearing loss and EES,
      the vestibular aqueduct may not appear dilated on CT. MRI is therefore necessary
      for correct diagnosis of this syndrome, which should more correctly be termed
      "large endolymphatic duct and sac syndrome". Prominent EES may predict poor
      prognosis in this syndrome.

PMID- 9561524
TI  - Sturge-Weber syndrome with no leptomeningeal enhancement on MRI.
AB  - Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by a
      facial nevus flammeus associated with seizures, developmental delay, and, often,
      with hemiparesis and hemianopia. On MRI, the most characteristic finding has been
      reported to be leptomeningeal enhancement, believed to represent leakage of
      contrast medium through the anomalous pial vessels that characterize the disease.
      We present a case of SWS with no evidence of leptomeningeal enhancement. This
      case illustrates that leptomeningeal enhancement need not be present in SWS, and
      the absence of this characteristic finding does not preclude the diagnosis.

PMID- 9561525
TI  - Giant arachnoid granulation mimicking dural sinus thrombosis in a boy with
      headache: MRI.
AB  - We report MRI and angiographic findings of an unusual giant arachnoid granulation
      in the left sigmoid sinus in a boy with headache. Its signal intensity was lower
      than that of cerebral cortex on T1-weighted images and higher on T2 weighting,
      mimicking dural sinus thrombosis.

PMID- 9561526
TI  - Magnetic resonance signal intensity and volume changes after endovascular
      treatment of intracranial aneurysms causing mass effect.
AB  - To determine when and how intracranial aneurysms causing mass effect change
      following endovascular treatment, we used MRI to assess patients for 2-3 years
      after the interventional procedure. Nine patients who had aneurysms compressing
      the surrounding structures underwent endovascular treatment. Proximal occlusion
      of the parent artery was performed in seven cases, and in two the aneurysm was
      embolised with microcoils. After embolisation, signal intensity within aneurysms
      tended to be high on both T1- and T2-weighted images. When there was rapid
      reduction in size high-signal zones within aneurysms became isointense or gave
      low signal on T1-weighted images. On T2-weighted images, isointense or low-signal
      foci appeared within high-signal areas in the aneurysm, giving mixed intensity.
      In typical cases, the mean volume of the aneurysm fell to approximately 30% of
      its initial value 2-12 months after treatment. After this, no additional
      reduction was observed. The aneurysms which showed little signal intensity change
      tended to shrink more slowly and to a lesser degree than the more typical cases.
      Aneurysms which gave high signal on both T1- and T2-weighted images early
      following embolisation shrank more quickly than those showing little signal
      change.

PMID- 9561527
TI  - Proton MR spectroscopy in vegetative patients.

PMID- 9561528
TI  - Overview of vascular disease.
AB  - Vascular disease in the pediatric population is a poorly understood process which
      is often underestimated in its incidence. The common beginnings of such
      ubiquitous diseases as atherosclerosis manifest themselves at a cellular level
      shortly after birth. Other common systemic disorders, including congestive heart
      failure and sepsis, are also intricately associated with dysfunctional
      vasculature. Progress in the understanding of normal and pathophysiologic
      processes within the vascular system begins with the "control center"--the
      endothelial cell. The purpose of this review is to consolidate a body of
      knowledge on the processes that occur at the cellular level within the blood
      vessel wall, and to simplify the understanding of how imbalances in these
      physiologic parameters result in vascular disease.

PMID- 9561530
TI  - The value of head ultrasound in infants with macrocephaly.
AB  - OBJECTIVE: To assess the value of head ultrasound (HUS) in neurologically normal
      infants with macrocephaly and to develop a rational approach to radiological
      investigation of macrocephalic infants. MATERIALS AND METHODS: A retrospective
      analysis of infants with macrocephaly (seen by one pediatric neurologist at this
      institution) was conducted. Infants with normal neurological examinations, no
      evidence of raised intracranial pressure and who had undergone a HUS were
      included. RESULTS: Twenty-seven infants were included in the analysis. Mean age
      at first assessment was 4.8 months. In 12 of 27 (44%), HUS was reported as
      normal. The remaining 15 had clinically insignificant abnormalities on HUS; 7 had
      prominent ventricles and 7 had increased subarachnoid fluid, with 1 infant having
      both. Seven infants had CT or MRI in addition to HUS. No clinically significant
      abnormalities were seen on CT or MRI scans that were not evident on HUS. Four
      infants had mild developmental abnormalities on initial evaluation. Mean duration
      of follow-up was 13.1 months. No infant developed neurological abnormalities
      during the follow-up period. CONCLUSION: In infants with macrocephaly with a
      normal neurological examination and no signs of raised intracranial pressure, HUS
      in conjunction with close neurological follow-up is reliable for the detection or
      exclusion of relevant intracranial pathology.

PMID- 9561529
TI  - Transcranial Doppler, MRA, and MRI as a screening examination for cerebrovascular
      disease in patients with sickle cell anemia: an 8-year study.
AB  - OBJECTIVE: The authors previously reported five transcranial Doppler
      ultrasonography (TCD) findings as significant in detecting clinical
      cerebrovascular disease in a 4-year study in patients with sickle cell disease.
      This is a follow-up to evaluate the validity of the original findings over
      another 4-year period during which the study population doubled. A clinical
      follow-up of the original asymptomatic sickle cell patients with positive TCD,
      MRA, and MRI was also made. MATERIALS AND METHODS: Over an 8-year period TCD,
      MRI, and MRA were prospectively performed in 90 sickle cell patients who were
      clinically asymptomatic for stroke and in 27 sickle cell patients with clinical
      stroke. RESULTS: Of the 4 out of original 46 control patients in 1992 who had
      positive MRA and TCD, 3 have subsequently had clinical stroke. None of the 9
      original patients with positive TCD and positive MRI but negative MRA have
      developed stroke. All five original TCD indicators of disease were still
      significant (P < 0.05) for detecting clinical disease: maximum velocity in
      ophthalmic artery (OA) > 35 cm/s, mean velocity in middle cerebral artery (MCA) >
      170 cm/s, resistive index (RI) in OA < 50, velocity in OA greater than in MCA,
      and velocity in posterior cerebral (PCA), vertebral, or basilar arteries greater
      than in MCA. An RI of < 60 in the DA was also now found to be significant
      [corrected]. Four additional factors were also significant: turbulence, PCA or
      ACA without MCA, RI < 30, and maximum velocity in MCA > 200 cm/s. CONCLUSION:
      Positive MRA with a positive TCD in an asymptomatic patient in long-term follow
      up suggests a trend for developing clinical stroke. A 4- to 8-year follow-up of
      nine patients with positive TCD, positive MRI, but not positive MRA did not show
      development of clinical stroke. Nine Doppler findings are significant in
      screening for clinically symptomatic vascular disease in sickle cell patients. It
      is recommended that children with sickle cell disease be screened for
      cerebrovascular disease with TCD. If one or two indicators of abnormality are
      present, MRA is recommended. If the MRA is positive, the patient may be
      considered for transfusion therapy or other treatment for prevention of stroke.

PMID- 9561531
TI  - Sonography of acute appendicitis in children: 7 years experience.
AB  - OBJECTIVE: The objective of this prospective study was to determine the accuracy
      in diagnosing appendicitis in children by using high-resolution graded
      compression sonography. MATERIALS AND METHODS: During a 7-year period, 3859
      children (mean age 9.9 years) with clinically suspected appendicitis were
      evaluated by sonography with the graded compression technique. The ultrasound
      results were correlated with the intraoperative and histopathological findings or
      clinical outcome. RESULTS: High-resolution sonography was performed in 3859
      children. Of the 610 patients who underwent a laparotomy, 494 had histologically
      proven acute or perforated appendicitis (prevalence 13%). In these children,
      sensitivity, specificity and overall accuracy of sonography were 90%, 97% and
      96%, respectively. The reasons for false-negative and false-positive results are
      discussed. CONCLUSION: Although the use of ultrasound to diagnose acute
      appendicitis in children has excellent results, the decision for surgery remains
      a clinical one because of the continuing false-negative and false-positive
      results from sonography.

PMID- 9561532
TI  - The role of micturating cystourethrography in antenatally detected mild
      hydronephrosis.
AB  - BACKGROUND: The postnatal imaging of infants with antenatally detected mild
      hydronephrosis remains controversial. OBJECTIVE: Our aim was to establish the
      role and timing of micturating cystourethrography (MCUG) in mild hydronephrosis.
      MATERIALS AND METHODS: We performed a retrospective study of 61 infants (122
      kidneys) referred with an antenatal diagnosis of hydronephrosis who showed
      persistent postnatal dilatation. All had follow-up postnatal ultrasound (US) and
      MCUG performed. The degree of dilatation at each follow-up scan was recorded.
      RESULTS: Of the 122 kidneys, 65 showed mild hydronephrosis. A substantial
      proportion of these (21.5%) demonstrated reflux. Serial US of these infants
      showed that the 6-week scan was the most informative and that any changes that
      warranted further investigation had occurred by this time. CONCLUSION: We
      recommend that all infants with mild hydronephrosis should undergo MCUG. MCUG
      need not be delayed until 3 months but could be performed following a 6-week US
      scan.

PMID- 9561533
TI  - Sonomorphology and involution of the normal urachus in asymptomatic newborns.
AB  - BACKGROUND: The number of reports on the sonomorphology of the urachus or urachal
      remnants in neonates and the pattern of involution is limited. OBJECTIVE: To
      determine whether a sonographically visible urachus in the first months of life
      is a pathologic condition and whether postnatal involution can be demonstrated by
      ultrasound. MATERIALS AND METHODS: A total of 102 asymptomatic infants (premature
      and term newborns) were examined with a high-resolution 7.5-MHz linear transducer
      between 0 and 60 days of age. In 70 infants, a second examination followed 3-5
      months later. RESULTS: In all infants, the urachus could be identified on the
      first examination. Different morphological types were differentiated. There was
      no difference between premature and term newborns in the morphology of the
      urachus. Spontaneous involution of the urachus was observed in all infants
      receiving a second examination, and they most often showed a fusiform urachal
      remnant at the apex of the bladder. CONCLUSION: Involution of the urachus is not
      complete at birth and can be followed up sonographically in the first months of
      life. This knowledge should prompt a new strategy in young infants with a
      discharging umbilicus or even an infected urachus. Instead of early surgery, a
      conservative approach under sonographic control seems reasonable, because there
      is a chance of spontaneous involution and any abnormal development can be
      detected by ultrasound.

PMID- 9561534
TI  - Wyburn-Mason syndrome: an unusual presentation of bilateral orbital and
      unilateral brain arteriovenous malformations.

PMID- 9561535
TI  - A comparison between digital fluoroscopic hard copies and 105-mm spot films in
      evaluating vesicoureteric reflux in children.
AB  - OBJECTIVE: To compare fluoroscopic freeze-frame digital images with conventional
      105-mm spot films during voiding cystourethrography (VCUG) with regard to
      diagnostic quality and radiation dose. MATERIALS AND METHODS: VCUG was performed
      on 57 consecutive children by a commercially available fluoroscopic digital
      system. Both freeze-frame digital images and conventional 105-mm spot films were
      obtained during 90 s of fluoroscopy. Skin radiation dose was assessed separately
      for spot films and for both fluoroscopy and spot films, employing
      thermoluminescent crystals on the anterior surface of the body. Patients were
      classified into three age groups: group A younger than 12 months, group B 1-5
      years old and group C 5-12 years of age. RESULTS: Digital and conventional images
      provided diagnostically identical results in 108 out of 114 ureters examined
      (94.7%). Percentage reductions in skin radiation dose due to the fluoroscopic
      hard copies compared with the four 105-mm radiographs were 53.8%, 50.5% and 57.1%
      for groups A, B and C, respectively. CONCLUSION: Substitution of conventional 105
      mm spot films during VCUG with digital fluoroscopic hard copies resulted in a
      substantial reduction in radiation dose. Digital images were as accurate as the
      conventional films in excluding vesicoureteric reflux (VUR). The two methods
      correlated well in diagnosing and grading VUR.

PMID- 9561536
TI  - The impact of extended radiology attending coverage in a children's hospital.
AB  - OBJECTIVE: In order to achieve more "timely" interpretation of radiologic
      examinations, a 3 to 11 p.m. attending radiologist slot was incorporated into the
      daily schedule utilizing existing staff. Our purpose was to assess the
      effectiveness of this practice by measuring report generation times. MATERIAL AND
      METHODS: Using a radiology information system (DecRAD), the time between
      completion of the technical examination and dictation of the official report for
      general (plain film) studies was determined for a 2-month period and compared to
      similar periods 1 and 2 years prior to instituting extended hours. Emergency and
      portable (ICU) exams were similarly analyzed. RESULTS: The number of examinations
      reported within 2 h of technical completion increased by 8.5% (mean); reporting
      within 4 h increased by 20%; reporting within 6 and 12 h of completion each
      increased by 24%. Over 80% of cases were dictated within 12 h after the change in
      practice occurred; whereas, it took up to 24 h in preceding years. Analysis of
      emergency and portable ICU exams showed similar trends, and the number of next
      day "call-backs" to the emergency department was significantly reduced.
      CONCLUSION: By extending attending coverage, more plain film examinations,
      especially emergency cases and ICU portables, were read and reported within a
      shorter time providing prompt communication with clinicians and more opportunity
      to influence management decisions.

PMID- 9561537
TI  - Torsion of an ovarian cyst mimicking enteric duplication cyst on transabdominal
      ultrasound: two cases.
AB  - We describe two girls with abdominal cysts which demonstrated the "double wall"
      or "muscular rim" sign. On the basis of this, the diagnosis of duplication cyst
      was made in each case. At surgery, both were found to have ovarian cysts, and
      histology revealed prominent haemorrhage within the cyst wall. To our knowledge,
      there has been no previous report of a false-positive "double wall sign".

PMID- 9561538
TI  - High-resolution ultrasound in the diagnosis of childhood malignant peritoneal
      mesothelioma.

PMID- 9561539
TI  - Multiple atresias with extensive intraluminal calcifications in a newborn with
      cystic fibrosis.
AB  - A newborn patient with cystic fibrosis and multiple intestinal atresias
      demonstrated intraluminal calcifications on a plain abdominal radiograph. Cystic
      fibrosis may be an aetiological factor for intraluminal calcifications secondary
      to multiple intestinal atresias.

PMID- 9561540
TI  - Ultrasonographic follow-up of the healing process of medically treated
      hypertrophic pyloric stenosis.
AB  - In hypertrophic pyloric stenosis (HPS), prompt pyloromyotomy is, in general, the
      treatment of choice. There has been no information available as to the natural
      history of the pyloric tumour. We present four infants with medically treated HPS
      who were followed by sonography to observe the anatomical changes that occur with
      atropine sulfate. The initial change was shortening of the pyloric canal,
      followed by thinning of the muscular layer as clinical symptoms improved.

PMID- 9561541
TI  - Perlman syndrome: a case report emphasizing its similarity to and distinction
      from Beckwith-Wiedemann and prune-belly syndromes.
AB  - Perlman syndrome is a rare entity characterized by hypotonia, facial dysmorphism,
      gigantism, and visceromegaly including nephromegaly. The current case illustrates
      the ultrasonographic and computed tomographic appearances of renal abnormalities
      in this condition. Findings in Perlman syndrome can overlap with and need to be
      distinguished from two more common clinical entities: prune-belly and Beckwith
      Wiedemann syndromes. Additional cranial findings previously unreported are also
      described.

PMID- 9561542
TI  - Hypercalcemia associated with dysgerminoma: case report and imaging findings.
AB  - Hypercalcemia associated with malignancy is rare in children. We report a case of
      hypercalcemia associated with ovarian dysgerminoma in a 13-year-old girl with
      renal medullary calcinosis and vascular calcifications. To our knowledge this is
      the first report of the imaging findings in this condition and only the fourth
      case report of hypercalcemia associated with dysgerminoma.

PMID- 9561543
TI  - Early cord degeneration in bifocal SCIWORA: a case report. Spinal Cord Injury
      Without Radiographic Abnormalities.

PMID- 9561544
TI  - MR imaging fails to detect bone marrow oedema in osteomyelitis: report of two
      cases.
AB  - Bone marrow oedema is the earliest and most sensitive sign in diagnostic imaging
      of osteomyelitis. In the two demonstrated cases of acute and chronic
      osteomyelitis, MRI was not able to detect bone marrow oedema due to accompanying
      haemosiderosis and sclerosis surrounding a bone abscess.

PMID- 9561545
TI  - Cervical spine injury in child abuse: report of two cases.
AB  - Pediatric cervical spine injuries have rarely been reported in the setting of
      child abuse. We report two cases of unsuspected lower cervical spine fracture
      dislocation in twin infant girls who had no physical examination findings to
      suggest cervical spine injury. Classic radiographic findings of child abuse were
      noted at multiple other sites in the axial and appendicular skeleton. Magnetic
      resonance (MR) imaging proved to be valuable in both the initial evaluation of
      the extent of cervical spine injury and in following postoperative changes. The
      unexpected yet devastating findings in these two cases further substantiate the
      importance of routine evaluation of the cervical spine in cases of suspected
      child abuse.

PMID- 9561546
TI  - The value of MRI in early Perthes' disease.

PMID- 9561547
TI  - Renal length changes with position.

PMID- 9561548
TI  - Cystic neuroblastoma identified by prenatal ultrasonography.

PMID- 9561549
TI  - Transcultural study of schizophrenic delusions. Tokyo versus Vienna and Tubingen
      (Germany).
AB  - Schizophrenic delusions of 324 inpatients in Tokyo, 101 in Vienna, and 150 in
      Tubingen (Germany) were compared according to the same classifications. Among the
      three areas, about 80% of the patients had equally 'negative' delusions (injury
      and/or belittlement), and about one-fourth had 'positive' delusions of grandeur.
      Transcultural influences were found in the detailed contents of the 'negative'
      delusions; specific and direct themes of persecutory delusion, i.e., delusions of
      poisoning, and religious themes of guilt/sin were conspicuous in Europe, while
      amorphous delusions of reference such as 'being slandered' were predominant in
      Japan. The latter may derive from the group-oriented self in Japanese 'shame
      culture'.

PMID- 9561550
TI  - Psychopathology in children of patients with panic disorder or animal phobia.
AB  - Several studies reveal a heightened risk for anxiety and other mental disorders
      in the offspring of patients with panic disorder and other anxiety disorders.
      Data on the specific type of transmitted disorders, however, are inconsistent. We
      investigated the specificity of the relationship between parents' and children's
      psychopathology. We assessed current and past mental disorders in 5- to 15-year
      old children of patients with panic disorder (CPAN, n = 34), children of parents
      with no diagnosis of a mental disorder (CCON, n = 30) and children of animal
      phobics (CPHOB, n = 23) using a structured diagnostic interview according to DSM
      III-R criteria. Diagnoses are based on parent as well as child information. CPAN
      and CPHOB had significantly more often at least one current mental disorder than
      children of the healthy control parents. Compared to CPHOB and CCON, children of
      panic patients had significantly more severe diagnoses and more often multiple
      diagnoses. Furthermore, a higher rate of internalizing anxiety disorders,
      particularly separation anxiety disorder, was found in CPAN. In contrast,
      children of animal phobics showed a higher rate of externalizing anxiety
      disorders. Our results suggest a specific transmission of such disorders that
      share common features of parental symptomatology.

PMID- 9561551
TI  - 'Alice in Wonderland' syndrome as a precursor of depressive disorder.
AB  - A 54-year-old Japanese businessman who was found to exhibit the 'Alice in
      Wonderland' syndrome and went on to develop a depressive disorder is described.
      Lengthening and shortening of time experience continued intermittently for about
      3 months, and metamorphopsia, distortion of body image, and the quick-motion
      phenomenon (alteration in time sense) persisted for almost 2 days without
      interruption. There were no abnormal physical findings. The authors review
      studies on 'Alice in Wonderland' syndrome and suggest that depressive illness may
      be a causal factor.

PMID- 9561552
TI  - Identifying misidentifications: a phenomenological study.
AB  - This study assessed how well the current classification system of the delusional
      misidentification syndromes (DMSs) represents the full range of misidentification
      phenomena encountered in self-descriptions of psychotic patients. To this end, a
      sample of 58 self-descriptions of ex-patients who had suffered from an episode of
      psychosis were reviewed. Misidentifications fitting the definition of one of the
      DMSs were identified in only 3 cases, whereas those fitting a general and broad
      definition were identified in 16 cases. It is argued that the restrictive nature
      of the currently dominant DMSs classification may have led to the neglect of a
      wide range of misidentification phenomena which do not fit the descriptions of
      any one of the classic DMSs. Proper identification, description and
      classification of these non-DMS misidentification phenomena is needed.

PMID- 9561553
TI  - The phenomenology of post-traumatic stress disorder. A symptomatic study of 70
      victims of psychological trauma.
AB  - This study analyses and categorises the subjective experiences and psychological
      symptoms of those involved in a major disaster but not themselves physically
      injured. It examines the concept of post-traumatic stress disorder (PTSD) and
      relates it to other psychiatric diagnoses and also to the particular nature of
      the disaster. 70 police officers are the subjects of this study, 59 men and 11
      women, all of them involved in the Hills-borough Football Stadium Disaster.
      Assessment included detailed psychiatric history and examination with an account
      of the events experienced by the informants and their psychological reaction to
      this at the time and subsequently. Psychiatric diagnosis was made and quantified
      measurements were also recorded, including a rating scale for the criteria of
      PTSD, the General Health Questionnaire and rating scales for depression and
      anxiety. Severity of PTSD symptoms was associated with higher scores on rating
      scales for both depressive and anxiety symptomatology. Subjective depressive
      symptoms and depersonalisation were associated with severity of PTSD. Frustrated
      helplessness was a recurring theme in the psychopathology. Alcohol consumption of
      those who were already drinkers increased. Social functioning at work and in
      marriage deteriorated with increased severity of PTSD. Although PTSD has features
      that distinguish it from other conditions, the degree of distress and long-term
      disability is more related to depressive symptomatology than to the severity of
      PTSD itself.

PMID- 9561554
TI  - Changes in myocardial ultrastructure induced by cooling as well as rewarming.
AB  - The aim of the present study was to investigate if hypothermia and rewarming,
      without accompanying cardiac ischaemia or cardioplegia, causes myocardial damage.
      Anaesthetized rats were subjected to a cooling procedure (4 h at 15-13 degrees C)
      where spontaneous cardiac electromechanical activity was maintained, followed by
      rewarming. Control rats, hypothermic rats and posthypothermic rats were perfusion
      fixed, the hearts removed and the ventricles examined using an electron
      microscope. Based on morphometric methodology volume fractions as well as
      absolute volumes of cellular and subcellular components of the ventricles were
      assessed. In hypothermic hearts capillary volume fraction was significantly
      decreased, which was probably due to a decrease in perfusion pressure. The
      cytosolic volume increased in both absolute values and as a fraction of the
      myocyte: from 25 +/- 11 in controls to 43 +/- 8 microliters and from 0.067 +/-
      0.023 to 0.102 +/- 0.013, respectively. There was a corresponding relative
      decrease in the volume fraction of myofilaments from 0.598 +/- 0.030 to 0.548 +/-
      0.024. In posthypothermic hearts significant tissue swelling was apparent,
      dominated by a significant increase in myocyte volume from 372 +/- 66 in controls
      to 522 +/- 166 microliters. Similar changes were measured in mitochondrial and
      cytosolic volumes. In conclusion, the myocardial ultrastructure was altered
      during hypothermia as well as after rewarming. Posthypothermic myocardium showed
      generalized cellular swelling and areas of cellular necrosis.

PMID- 9561555
TI  - Myocardial fatty acid metabolism during acute cardiac allograft rejection.
AB  - Fatty acids are promptly taken up, metabolised and eliminated by healthy
      cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are
      known to be associated with an impaired fatty acid metabolism. It was the aim of
      this study to investigate fatty acid metabolism in a rat heart transplant model
      and to correlate scintigraphic findings with histological changes. After right
      side nephrectomy of Lewis recipients Brown Norway cardiac allografts were
      anastomosed to the renal vessels. Animals were given no immunosuppression. The
      metabolism of carrier-free 17-123 jodo-heptadecanoic acid (123J-HDA) with a
      specific activity of > 2 x 10(17) Bq/ml was scintigraphically measured between
      days 1 and 11. An increase in the grade of rejection was observed over time.
      Fifty-six frames of 30 s duration each were recorded. For the region of interest
      (native heart, transplanted heart, left kidney) frames 10-56 were superimposed,
      time-activity curves generated and monoexponentially fitted. Furthermore,
      elimination half-life and intercepts were calculated. Following scintigraphic
      evaluation the animals were killed and graft as well as native hearts excised for
      histological examination. The uptake of the tracer identified severe grades of
      rejection. Elimination half-life of the tracer was twice as long from hearts with
      mild rejection and more than 14 times as long in severe rejection compared with
      no rejection. Elimination half-life and amplitude did not permit discrimination
      between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4.
      This method therefore seems to be a valuable tool for the noninvasive detection
      of severe acute cardiac allograft rejection. Since fatty acid metabolism is
      clearly stress-dependent it remains to be seen whether this method allows
      detection of earlier rejection in loaded hearts.

PMID- 9561556
TI  - Fascioperitoneal graft with T-tube drainage for patching bile duct defects.
AB  - Reconstruction of choledochal wall defects in an experimental dog model by T-tube
      plus fascioperitoneal graft and an evaluation of the short-term results were the
      aims of this study. Twelve randomly selected mongrel dogs of both sexes, having
      an average weight of 22.15 +/- 1.85 kg, were anaesthetized with ketamine HCI and
      xylazine and underwent laparatomy. The front wall of choledoch canal were excised
      with its all layers 0.5 cm in diameter at the distal part of the cystic duct
      junctions. These defects were repaired by using grafts prepared of the same
      diameter from the dorsal fascias of rectus muscles and peritoneum. T-tubes were
      introduced into the common ducts on the proximal part of the grafts. One of the
      animals died in the postoperative period due to evantration. T-tube
      cholangiograms on the twelfth day did not indicate any extravasation or
      stricture. Histopathological examination of the graft regions on the sixtieth day
      revealed that the epithelialization had commenced on the border between the bile
      epithelium and grafts. Based on these early findings, it was suggested that if
      supported by further studies it may be thought of as a clinical method.

PMID- 9561557
TI  - The effect of sodium based hypo-osmolality on arterial smooth muscle reactivity
      in vitro.
AB  - The study tested the hypothesis that the reduced [Na+]e and hypo-osmolality of
      normal pregnancy are causally linked to the attenuation of vascular smooth muscle
      reactivity in vitro. Aortic rings from nonpregnant female rats were incubated in
      physiological medium containing 114 mM NaCl/l and the contractile responses to
      phenylephrine, KCl and CaCl2 as well as the relaxations to acetylcholine and KCl
      were compared with those of rings incubated in normal medium containing 119 mM
      NaCl/l. There was no solute substituted for the lowered [Na+]. Experiments with
      phenylephrine were repeated using de-endothelialized rings and intact rings
      pretreated with indomethacin. Contractile responses of intact rings (n = 11) in
      hypo-osmolar solution to phenylephrine were significantly (P < 0.001) lower than
      of those in normal medium (n = 11). Responses were partially restored by
      endothelial denudation but not in the presence of indomethacin. Relaxations to
      acetylcholine (n = 7 for hypo-osmolar; n = 6 for normal solution) and KCl (n = 7
      for each of hypo- and normal osmolar) were significantly enhanced (P < 0.05) in
      rings incubated in hypo-osmolar solution. There was no significant difference
      between the responses of the rings to KCl, and CaCl2 in either solution. These
      effects are similar to some of those previously described for vascular smooth
      muscle in normal pregnancy suggesting that the reduced [Na+]e and hypo-osmolarity
      of normal pregnancy may be contributing to the diminished vascular reactivity.

PMID- 9561558
TI  - Asymmetry of sympathetic activity in a rat model of Parkinson's disease induced
      by 6-hydroxydopamine: haemodynamic, electrocardiographic and biochemical changes.
AB  - We studied the effects of experimental hemiparkinsonism upon sympathetic function
      in rat. The rats were divided into three groups: a group given intact control,
      one given lesioning with 6-hydroxydopamine (6-OHDA), and one given sham
      operation. One day after apomorphine testing following lesioning of the
      substantia nigra (SN) with 6-OHDA, heart rate (HR), mean arterial blood pressure
      (MAP), and electrocardiogram (ECG) were monitored. Plasma norepinephrine (NE),
      epinephrine (E), and dopamine (DA) levels were measured. Thereafter,
      immunohistochemical examination was performed to detect the extent of 6-OHDA
      lesions, using the avidinbiotinylated peroxidase complex (ABC) method. There was
      no difference in the total number of tyrosine hydroxylase (TH)-positive cells and
      rotation responses between the right- and left-sided 6-OHDA-treated groups. On
      the other hand, injury of rats with unilateral 6-OHDA resulted in haemodynamic,
      electrocardiographic, and biochemical changes. A significant difference was found
      between the right-sided 6-OHDA-treated rats and the left-sided treated ones. The
      MAP increased in the group given left 6-OHDA treatment and to lesser extent in
      the sham-operated group. In contrast, MAP did not increase in the group given
      right 6-OHDA treatment and was significantly lower than values in both the intact
      control rats and the sham-treated rats. Also, only the group given right 6-OHDA
      injury showed a fall in the value of HR. The plasma NE level was significantly
      decreased in the group given right 6-OHDA treatment compared with all other
      groups (P < 0.005). Our results indicate that right-sided lesioning of the
      nigrostriatal DA pathway in the central nervous system (CNS) has greater
      sympathetic consequences than left-sided ones. These results also suggest that
      there is a differential effect of right-sided SN lesions on sympathetic cardiac
      innervation. The mechanism behind the confronting impairment of autonomic nervous
      system (ANS) could in this experiment be attributable to an asymmetric
      representation of sympathetic function in the brain. However, further studies
      will be needed before final conclusions can be made.

PMID- 9561559
TI  - Beneficial effects of pentoxifylline treatment of experimental acute pancreatitis
      in rats.
AB  - The purposes of this study were to determine the tumor necrosis factor (TNF) and
      interleukin-6 (IL-6) levels after the induction of acute necrotizing
      pancreatitis, and to establish the effects of pentoxifylline on cytokine
      production. METHODS: acute pancreatitis was induced by the retrograde injection
      of 200 microliters taurocholic acid into the pancreatic duct in male Wistar rats.
      The serum amylase activity, the wet pancreatic weight/body weight ratio, and the
      TNF and IL-6 levels were measured. Seven mg/kg pentoxifylline were administered
      intraperitoneally at the time of operation 6, 12 or 24 h later. Rats were killed
      6, 24, 48 or 72 h after the operation. RESULTS: the TNF bioassay revealed high
      levels of TNF (30.2 +/- 5.4 U/ml, 35.0 +/- 5.0 U/ml and 36.6 +/- 6.0 U/ml) in the
      control group at 6, 24 and 48 h and (54.1 +/- 20 U/ml and 10.9 +/- 4.2 U/ml) in
      the pentoxifylline-treated group at 6 and 24 h, respectively, whereas the level
      had decreased to zero in the pentoxifylline-treated group at 48 h. The IL-6
      bioassay likewise demonstrated high levels of IL-6 in the control group at 48 h
      and in the pentoxifylline-treated group at 6 and 24 h, and markedly decreased
      levels in the pentoxifylline-treated group at 48 h (7083 +/- 2844 pg/ml, 6463 +/-
      1307 pg/ml, 10,329 +/- 5571 pg/ml vs 137.5 +/- 85.5 pg/ml, respectively, P <
      0.05). The high mortality observed in the pancreatitis group (43%) was decreased
      by pentoxifylline administration to 11%. CONCLUSION: these results demonstrate
      that pentoxifylline very effectively inhibits cytokine production in acute
      pancreatitis.

PMID- 9561560
TI  - Study of the immunogenicity of different recombinant Mengo viruses expressing
      HIV1 and SIV epitopes.
AB  - Recombinant Mengo viruses expressing heterologous genes have proven to be safe
      and immunogenic in both mice and primates, and to be able to induce both humoral
      and cellular immune responses (Altmeyer et al., 1995, 1996). Several recombinant
      Mengo viruses expressing either a large region (aa 65-206) of the HIV1 nef gene
      product, or cytotoxic T lymphocyte (CTL) epitopic regions from the SIV Gag (aa
      182-190), Nef (aa 155-178) and Pol (aa 587-601) gene products were engineered.
      The heterologous antigens were expressed either as fusion proteins with the Mengo
      virus leader (L) protein, or in cleaved form through autocatalytic cleavage by
      the foot-and-mouth disease virus 2A protein. Rhesus macaques and BALB/c mice
      inoculated with the Mengo virus SIV recombinants failed to develop CTL responses
      against the SIV gene products, while one of the HIV-Nef recombinants induced a
      weak CTL response in mice directed to an HIV1 Nef peptide spanning positions 182
      198. In contrast, BALB/c mice immunized with vaccinia virus recombinants
      expressing HIV1 Nef developed a strong CTL response to the 182-198 peptide and
      also responded to a second peptide spanning positions 73-81. These results
      indicate that Mengo virus recombinants expressing HIV1 Nef and SIV CTL epitopes
      are weak immunogens. One of the fusion recombinants expressing SIV CTL epitopes
      failed to infect macaques even when used at high doses, while the recombinant
      expressing HIV1 Nef as a fusion protein failed to infect BALB/c mice. These
      results demonstrate that the expression of certain heterologous sequences as
      fusion proteins with L can result in the loss of the ability of the recombinant
      to infect normally susceptible animals.

PMID- 9561561
TI  - Interleukin-4 regulation of cytokine-induced HIV1 and interleukin-8 expression in
      promonocytic U1 cells is concentration- and cytokine-dependent.
AB  - IL4 has been shown to differentially modulate HIV1 replication in primary cells
      of the monocyte/macrophage lineage. Its effects on chronic HIV1 infection,
      however, are unknown. To address IL4-mediated effects on promonocytic cells
      chronically infected with HIV1, U1 cells were incubated in the presence or
      absence of IL4 together with cytokines that are known to induce both HIV1 and IL8
      expression. IL4 enhanced IL1 beta-induced HIV1 and IL8 expression in promonocytic
      U1 cells, whereas it suppressed their expression induced by cytokines IL6, GM-CSF
      and to a small extent, TNF alpha. IL4 suppressed IFN gamma-induced IL8 production
      with increasing IL4 concentration, while HIV1 p24 core antigen production was
      suppressed at low IL4 input (0.1 and 1 U/ml) but was substantially enhanced at a
      high IL4 input concentration (10 U/ml). Results showed that the immunosuppressive
      cytokine IL4 can behave variably in modulating HIV1 and IL8 expression, depending
      on both the inducing cytokine and the input concentration of IL4.

PMID- 9561562
TI  - Glycoprotein B of Aujeszky's disease virus: topographical epitope mapping and
      epitope-specific antibody response.
AB  - A panel of 26 monoclonal antibodies (mAbs) against glycoprotein B (gB) of
      Aujeszky's disease (pseudorabies) virus (ADV), a glycoprotein complex consisting
      of three glycoproteins, gBa, gBb, and gBc, was produced by two research groups
      and was used for the topographical epitope mapping of gB. An epitope map was
      constructed in which the identified epitopes of gB were situated in 14
      topologically distinct antigenic domains; ten antigenic domains represented by 22
      mAbs were localized on gBc, while four antigenic domains represented by four mAbs
      resided on gBb of the gB complex. All the epitopes located on gBc appeared to be
      conformation-dependent, whereas all the epitopes on gBb were conformation
      independent. The identified epitopes of gB were conserved among laboratory,
      vaccine and field ADV strains. Conformation-dependent epitopes were shown to
      contribute largely to the overall antibody response to gB in naturally infected
      swine and immunized mice. Moreover, it was found that most of the infected
      animals responded relatively weakly to the identified conformation-independent
      epitopes of gB, while a group of immunodominant epitopes that induced a strong
      antibody response was represented exclusively by conformation-dependent epitopes
      from different antigenic domains. The results clearly demonstrated that
      conformation-dependent epitopes of gBc play a crucial role in inducing the
      humoral immune response to gB of ADV during the natural infection of swine and
      immunization of mice. The application of mAbs of our panel as research and
      diagnostic tools is discussed.

PMID- 9561563
TI  - Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1
      human immunodeficiency virus long terminal repeat.
AB  - The transcription of HIV1 provirus is regulated by both cellular and viral
      factors. Various evidence suggests that Tat protein secreted by HIV1-infected
      cells may have additional action in the pathogenesis of AIDS because of its
      ability to also be taken up by non-infected cells. Curcumin [diferuloylmethane or
      1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the yellow
      pigment in turmeric Curcuma longa (Linn). It exhibits a variety of
      pharmacological effects including antiinflammatory and antiretroviral activities.
      Here, we demonstrated that curcumin used at 10 to 100 nM inhibited Tat
      transactivation of HIV1-LTR lacZ by 70 to 80% in HeLa cells. In order to develop
      more efficient curcumin derivatives, we synthesized and tested in the same
      experimental system the inhibitory activity of reduced curcumin (C1), which lacks
      the spatial structure of curcumin; allyl-curcumin (C2), which possesses a
      condensed allyl derivative on curcumin that plays the role of metal chelator; and
      tocopheryl-curcumin (C3), which enhances the antioxidant activity of the
      molecule. Results obtained with C1, C2 and C3 curcumin derivatives showed a
      significant inhibition (70 to 85%) of Tat transactivation. Despite the fact that
      tocopheryl-curcumin (C3) failed to scavenge O2.-, this curcumin derivative
      exhibited the most activity; 70% inhibition was obtained at 1 nM, while only 35%
      inhibition was obtained with the curcumin.

PMID- 9561564
TI  - Variation in virological parameters and antibody responses in macaques after
      atraumatic vaginal exposure to a pathogenic primary isolate of SIVmac251.
AB  - We developed an animal model for the male-to-female transmission of human
      immunodeficiency virus, consisting of an atraumatic vaginal application of simian
      immunodeficiency virus onto the intact vaginal mucosa of cynomolgus macaques.
      Different doses of a pathogenic isolate of SIVmac251, with or without seminal
      plasma, were infused into the vaginas of female macaques. Infection of macaques
      could be achieved after a single exposure to the virus. Two patterns of infection
      were underscored with no relation to the virus dose inoculated: in 50% of the
      monkeys, SIV was persistently recovered and a strong antibody response to SIV was
      evidenced in blood and vaginal secretions. In the other infected animals, SIV
      infection was only transiently evidenced and a weak systemic antibody response
      was detected. It appeared that the presence of seminal plasma may be implicated
      in this variability only when low doses of virus are inoculated. Sequence
      analysis of the env gene of SIV revealed that most of the persistently viraemic
      animals were infected with a viral variant different from that of transiently
      viraemic macaques.

PMID- 9561565
TI  - Cryptorchidism--aspects of pathogenesis, histology and treatment.
AB  - Cryptorchidism is the absence of at least one testis in the scrotum. The
      incidence of cryptorchidism is high and almost 3% of boys in the western
      countries are operated on for this condition. Abnormalities in the hypothalamo
      pituitary-testicular axis may result in cryptorchidism, and cryptorchidism is
      nearly almost present in individuals with a testis and abnormal sexual
      differentiation. We characterized an association of cryptorchidism and T10-S5
      vertebral, renal and ureteral malformations and dysplasias. Cryptorchidism was
      ipsilateral to renal and ureteral malformations and dysplasias in more than 90%
      of cases. The association was proved with increasing frequency in: 4-10% of
      cryptorchid boys who had undergone laparoscopy for impalpable testes or were
      expected to be without additional abnormalities; 18% of cryptorchid boys in a
      material from a department of pediatric surgery; 34% of cryptorchid individuals
      who had died between week 28 and 40 of gestation; 65% of cryptorchid boys
      operated on for imperforate anus; all individuals with tritonmelia who are always
      cryptorchid. As the association was demonstrated with increasing frequency the
      higher the degree of abnormal differentiation of the caudal developmental field,
      cryptorchidism may be interpreted as a feature of such an abnormal
      differentiation. The general significance of our hypothesis is supported by the
      fact that both position and histology of the undescended testes were independent
      of a possible presence of the malformations and dysplasias encompassed by the
      association. Intra-abdominal testes were associated with persisting diaphragmatic
      ligaments which again were associated with an abnormal differentiation of the
      midline. Consequently we consider cryptorchidism a feature of abnormalities in
      the hypothalamo-pituitary-testicular axis and of an abnormal differentiation of
      the male sexual organs, the midline, and/or the caudal developmental field. The
      recommended age at surgery for cryptorchidism has gradually been lowered. The
      recommendations are mainly based on analyses of number of spermatogonia per
      tubular transverse section in normal and undescended testes. In 1984 when we
      started our investigations, the biological value of this variable was
      unclarified.

PMID- 9561566
TI  - Changes in morphology, function and blood flow in mini-pig urinary bladder after
      chronic outflow obstruction and recovery from obstruction.

PMID- 9561567
TI  - NGF-beta, NE-cells and prostatic cancer cell lines. A study of neuroendocrine
      expression in the human prostatic cancer cell lines DU-145, PC-3, LNCaP, and TSU
      pr1 following stimulation of the nerve growth factor-beta.
AB  - Neuroendocrine (NE) cells are present in both benign and malignant human
      prostate. However, their function is poorly understood, mainly due to the lack of
      suitable experimental models. The nerve growth factor-beta (NGF-beta) promotes
      the rat pheochromocytoma cell line PC-12 to differentiate into neuronal like
      cells. We have studied the effect of NGF-beta on four human prostate cancer cell
      lines, LNCaP, DU-145, PC-3, and TSU-pr1. NGF-beta stimulates the growth rate in
      all these cell lines, but does not induce a neuronal phenotype. NE tumour markers
      (chromogranin A [CgA] and chromogranin B[CgB]) could not be demonstrated by
      immunocytochemistry (CgA and CgB), Northern blotting (CgA), or ELISA techniques
      (CgA), neither in control nor in NGF-beta stimulated cells. Consequently, other
      experimental models have to be sought in the study of NE cells in the human
      prostate.

PMID- 9561568
TI  - Ureteric profilometry. A study of the ureteric pressure profile in the normal and
      pathologic ureter.
AB  - The ureteric pressure profile in the normal and pathologic ureter was studied. A
      3F ureteric catheter was introduced through the ureteric orifice up to the mid
      renal pelvis, and was connected to a pressure transducer. The catheter was pulled
      down to the urinary bladder and during withdrawal the pressures in the renal
      pelvis, uretero-pelvic junction (UPJ), ureter, ureterovesical junction (UVJ) and
      urinary bladder were recorded. The normal ureteric pressure profile started with
      a peak rise at the UPJ followed by a drop and fluctuations representing the
      peristaltic waves, and ended with a peak rise at the UVJ. The strictured
      moderately dilated ureter showed peristaltic waves with irregular rhythm and
      pressure amplitude, a condition we call "ureteroarryhthmia". The hugely dilated
      ureter exhibited no waves, i.e. a "silent" profile. The refluxing ureter with
      normal caliber showed an ureteroarrhythmic pressure profile, while the dilated
      ureter exhibited either a ureteroarrhythmic or a silent pattern. The study could
      define a characteristic profilometric pattern for the normal ureter. Two
      pathologic patterns could be identified: ureteroarrhythmic and silent. Ureteric
      pressure profilometry is suggested acts as a diagnostic tool in the various
      pathologic conditions of the ureter.

PMID- 9561569
TI  - Lower urinary tract symptoms. A comparison of micturition symptoms in patients
      scheduled for transurethral prostatic resection and outpatients of both sexes
      referred for non-urological complaints.
AB  - The presence of ten different micturition symptoms was investigated by means of a
      patient-administered questionnaire in 355 males and females over 50 years of age
      referred for non-urological complaints, and compared to those of 131 patients
      selected for transurethral prostatic resection (TURP) due to symptomatic benign
      prostatic hypertrophy. Each symptom was evaluated further by a subsequent
      "bother" question and the questionnaire also contained a global "bother"
      question. Each of the symptoms was significantly more frequent and pronounced in
      the TURP group than in the control group. Moderate or severe symptoms were found
      in 25% of males and 18% of females in the control group as compared to 92% in the
      TURP group. In the control group most symptoms increased with age regardless of
      sex, and this was most pronounced for weak stream and hesitancy. Males in the
      control group had a significantly higher total symptom score than females (5.3 vs
      4.3; p < 0.05). This difference was, however, mainly due to higher scores in weak
      stream, hesitancy and post-micturition dribbling in males. Females tended to have
      more urgency. The symptom scores and the associated "bother" scores were highly
      correlated, indicating that each symptom carried the same potential to bother the
      patient. The single global "bother" question gave an adequate reflection of the
      combined "bother" scores, and seems sufficient in the evaluation of the
      individual patient's concern.

PMID- 9561570
TI  - Management of benign prostatic hyperplasia in Scandinavia. A hospital
      questionnaire on pretreatment evaluation and treatment. The Scandinavian Urologic
      Association Subcommittee on Benign Prostatic Hyperplasia.
AB  - In order to describe the present status in Scandinavia of evaluation and
      treatment of patients presenting with symptomatic benign prostatic hyperplasia
      (BPH), a questionnaire was mailed to 261 relevant hospitals. In total 76% of the
      departments answered. Several differences between hospital types in each country
      were revealed, as well as differences between countries. Generally, symptom
      scores and urodynamics were used more often in university hospitals as compared
      to other types of hospitals. Symptom scores were most popular in Denmark and
      Sweden, while uroflowmetry generally was employed in Denmark and Finland, but
      less frequently in Sweden and Norway. The highest frequency of prostatic surgery
      was noted in Denmark. Watchful waiting accounted for the handling of 30% of the
      BPH patients in Finland and Sweden, in contrast to only 15% in Denmark.

PMID- 9561571
TI  - Sexual function one year after transurethral prostatic resection. Patients' own
      assessments.
AB  - One year after transurethral resection of the prostate for benign hyperplasia,
      127 men received a questionnaire requesting personal evaluation of sexual
      function, including erection, ejaculation, libido and satisfaction. Significant
      postoperative dysfunction was reported in all these respects: 54% of the
      responders claimed deterioration and half of them blamed the operation. Decline
      in sexual function had a multifactorial background, including advancing age,
      morbidity, and changed marital and social conditions. Although other examinations
      with preoperative and postoperative evaluation report a lower incidence of
      impotence development, which may be more reliable, it is psychologically
      interresting that the patients themselves suspect the transurethral resection as
      the cause of impaired sexuality.

PMID- 9561572
TI  - Variations in the diagnostic process among urologists in one region recorded
      using an interactive computer program.
AB  - To analyse how male cases suffering from lower urinary tract symptoms (LUTS) due
      to benign prostatic hyperplasia (BPH) are handled within a well-defined health
      care region in Scandinavia, an interactive computer program containing 20 cases
      suffering from LUTS due to BPH was used for recording the diagnostic process and
      the treatment decisions; 37 out of a total of 50 urologists practicing within a
      small health region participated. The diagnostic process varied considerably due
      to a varying choice of diagnostic tests and the large differences in interpreting
      the qualities described by the tests. The probability that a patient would be
      offered a treatment within the region was analysed. For many patients the
      probability that a treatment was chosen was in the vicinity of 50%. No treatment
      probability was correlated to the symptom score of the patients. While the
      probability that a transurethral prostatic resection would be offered to the
      patients within the region was correlated significantly to urodynamic variables,
      residual urine and to cystoscopy findings, the probability that transurethral
      microwave or finasteride therapy would be offered was not correlated to any of
      the described qualities. The costs of the diagnostic process in all the patients
      incurred by each of the urologists varied by up to 500%. It was estimated that
      approximately 40% of the costs involved diagnostic tests that did not influence
      the decision to offer or not to offer treatment. In conclusion, the enormous
      variations in the handling of the cases recorded in the study stress the need
      that a management formula should be used in the handling of patients with LUTS.

PMID- 9561573
TI  - Non-prosthetic surgery in the treatment of erectile dysfunction. A retrospective
      study of 45 impotent patients in the University of Oulu.
AB  - The purpose of this retrospective study was to assess the outcomes of the
      patients with total erectile impotence who have undergone non-prosthetic surgery
      in our hospital and to make a decision concerning the continuation of this
      treatment modality. The study series consisted of 45 operated patients, 21 of
      whom had undergone venous leakage surgery and 24 revascularization of the penis.
      The follow-up time was at least 12 months. The outcome of venous surgery after 6
      months was initially good in 16 patients (76%) but declined in such a way that 12
      months after the operation it was good only in 6/21 patients (29%). Despite this,
      11/21 patients were capable of intercourse after a prostaglandin E1 injection 1
      year from the operation. Altogether 17/21 patients (81%) benefited from venous
      surgery after 12 months. The outcome of arterial surgery was good in 11/24
      patients (46%) 12 months after the operation. A moderate outcome was obtained in
      another 8/24 patients (33%), who were capable of intercourse after a
      prostaglandin E1 injection. Minor complications occurred in 20% of the venous
      surgery patients; 25% of the patients with arterial surgery had complications and
      half of these were severe, resulting in glans hypervascularization. Our findings
      indicate that non-prosthetic surgery continues to have an established position in
      the treatment of severe impotence when all conservative treatment modalities have
      been used.

PMID- 9561574
TI  - Biomechanical properties of normal and varicose internal spermatic veins.
AB  - To investigate possible differences in biomechanical properties between varicose
      spermatic veins and controls. During surgery on 12 patients for grade 3 left
      sided varicocele testis, 2 cm of the vein was obtained for comparison with: (i)
      samples of the left internal spermatic vein taken from the same anatomical
      localization from 8 patients without scrotal disease, and (ii) samples from the
      right internal spermatic vein from 7 other patients also without scrotal disease.
      The biomechanical properties of ring-shaped venous specimens were investigated by
      loading the specimen at a constant deformation rate until rupture. The relative
      amounts of collagen in the specimens were determined as the contents of
      hydroxyproline. There was a significant difference between varicocele
      testis/right spermatic vein in UC (unit collagen), F-max (maximum strength),
      Strain (ultimate extensibility) and E-fail (relative failure energy), but not in
      LD (diameter) and Tan-a (stiffness of the specimen). There were no significant
      differences between left and right spermatic vein in LD, UC, F-max, Strain, Tan-a
      and E-fail. There was a significant difference in LD between varicocele
      testis/left spermatic vein, but no relationship in UC, F-max, Strain, Tan-a and E
      fail. Biomechanical analyses of the spermatic veins from patients operated for
      varicocele seem to support the hypothesis that a difference in biomechanical
      properties plays a part in the development of varicocele because a significant
      increase in extensibility of varicocele samples was found compared with normal
      right spermatic vein samples.

PMID- 9561575
TI  - Primary hydatid cyst of the adrenal gland.
AB  - An extremely rare case of primary hydatid cyst of the adrenal gland is reported.
      Adrenal hydatid cysts are usually a manifestation of generalized echinococcosis.
      Only nine primary cases have so far been reported in the literature. The
      presentation is insidious. Correct preoperative diagnosis is difficult. Clinical
      and investigative findings are non-specific and ambiguous. Surgery is the
      treatment of choice.

PMID- 9561576
TI  - Renal angiomyolipoma with haemorrhage treated by urgent embolization.
AB  - We present herein a case of bleeding angiomyolipoma with disruption of the renal
      capsule, which was treated by hyperselective embolization of the corresponding
      renal artery branch.

PMID- 9561577
TI  - Renal vein thrombosis caused by laparoscopic cholecystectomy.
AB  - A 48-year-old woman was diagnosed with right renal vein thrombosis (RVT) 2 weeks
      after a laparoscopic cholecystectomy. The patient had none of the major risk
      factors for RVT or deep vein thrombosis. She was treated with long-term
      anticoagulation. Complete dissolution of the thrombi was reached 1 month after
      diagnosis.

PMID- 9561578
TI  - The natural history of metachronous renal cell carcinoma.
AB  - A case of metachronous renal cell carcinoma is reported in a 52-year-old male
      patient who had previously undergone radical nephrectomy for cancer in 1989. He
      was thereafter monitored with annual CT-scans. In January 1994, a small, solid,
      renal parenchymal mass was detected in the opposite kidney. Following that, three
      consecutive abdominal CT-scans were carried out over the year in order to
      evaluate any changes. Subsequently, elective right nephron-sparing resection was
      performed. This report discusses neoplasm detection, evolution and clinical
      approach in a patient with previous nephrectomy for cancer.

PMID- 9561579
TI  - Glomerulonephritis associated with basaloid squamous cell carcinoma of the
      oesophagus. A possible unusual paraneoplastic syndrome.
AB  - A 70-year-old man presented with rash, microscopic haematuria and proteinuria.
      The renal biopsy showed mesangial proliferative glomerulonephritis with mesangial
      IgA deposition. He was subsequently found to have basaloid squamous carcinoma of
      the oesophagus. This possible association between IgA nephropathy and oesophageal
      basaloid squamous carcinoma has never been reported.

PMID- 9561580
TI  - Renal hypertension due to giant perirenal haematoma: permanent resolution by
      percutaneous ultrasound-guided drainage.
AB  - We describe a case of renovascular hypertension accompanied by renal failure,
      arising in a young man with a solitary kidney 4 months after a blunt abdominal
      trauma. A giant haematoma was found around the right kidney and ultrasound-guided
      percutaneous drainage completely relieved the symptom complex. Nine years later,
      the patient is normotensive with normal renal function.

PMID- 9561581
TI  - Embryonal adenoma of the kidney. A rare embryonal adenoma of the kidney.
AB  - We report the case of a 47-year-old man who underwent partial nephrectomy for an
      embryonal adenoma which was characterized by a monomorphous appearance. No
      adjuvant therapy was given and at the 5-year follow-up the patient is in perfect
      health and no relapse has been observed.

PMID- 9561582
TI  - Primary adenocarcinoma of distal ileum used as outlet from a right colonic
      urinary reservoir.
AB  - A case of primary adenocarcinoma of distal ileum used as intussuscepted nipple
      valve and outlet from a right colonic reservoir is reported. The tumour was
      diagnosed 5.5 years after the patient was operated on with cystectomy and right
      colonic reservoir for a moderately differentiated, muscle-invasive transitional
      carcinoma of the bladder.

PMID- 9561583
TI  - Metastatic transitional cell carcinoma of the ovary from superficial bladder
      tumour.
AB  - A 60-year-old female underwent transurethral resection of superficial grade 2
      transitional cell carcinoma (TCC) of the urinary bladder. Six months later,
      intravesical Mitomycin C instillation was given following two superficial
      recurrences. A further recurrence of TCC grade I was resected transurethrally 39
      months later. Forty-eight months after the original diagnosis the patient
      developed an abdominal mass, which turned out to be TCC grade 3 involving the
      left ovary. She underwent laparotomy which showed a left ovarian mass. Total
      abdominal hysterectomy, bilateral oophorectomy and partial omentectomy were
      carried out. She developed pelvic metastases 3 months later and died.

PMID- 9561584
TI  - Prenatal diagnosis of cloacal anomaly.
AB  - The authors present a case of prenatal diagnosis of cloacal anomaly,
      characterized by the presence of oligohydramnios and cystic pelvic mass with
      changing features during observation. Postnatal study confirmed the presence of a
      recto-cloacal fistula, with a high confluence of the urinary, genital and
      intestinal systems. Both parents had a chromosome 9 inversion (p11q13), but the
      child was chromosomally normal.

PMID- 9561585
TI  - [Complement and its role in immune response].
AB  - The complement system as a part of innate immunity is considered to provide rapid
      tough incomplete antimicrobial activity. However, besides providing a first-line
      defence, innate immunity plays additional important roles: it initiates and
      improves the slower, but more specific, acquired immune response. The recognition
      and destruction of noxious substances, as well as initiation of the acquired
      immune response, are accompanied by potentially hazardous inflammation. The
      inflammatory process has thus to be tightly regulated. In this overview, innate
      immunity and its interactions with acquired immunity are discussed with the main
      focus on the complement system. Our scientific interests are integrated into the
      discussion on complement.

PMID- 9561586
TI  - [Clinical value of measuring systolic arterial blood pressure post-exercise for
      evaluation and diagnosis of coronary disease: comparative study between women and
      men].
AB  - It has been demonstrated that the ratio of the systolic blood pressure post
      exercise to that at peak exercise (rSBP) is a criterion for diagnosis and
      severity of coronary artery disease (CAD) in men. No such demonstration has been
      attempted in women. We have compared SBP to classical signs of ischemia, such as
      ST segment depression and angina pectoris, in a group of 788 ambulatory patients
      of whom 357 were women. All underwent a bicycle ergometric test and a coronary
      angiogram. The prevalence of CAD at angiography was the same for both genders
      (women 43.5% and men 47%) with no significant difference in the number of vessels
      diseased. In patients with CAD, the rSBP was significantly more elevated than in
      others, at 1 minute (p < 0.01) and even more so at 3 minutes (p < 0.001) post
      exercise, with no gender difference. The most discriminating value of rSBP at 3
      minutes post-exercise for diagnosis of CAD was situated at 0.91 for sensitivity
      and specificity (receiver operating characteristic curve analysis). In the whole
      group sensitivity of rSBP is lower, while the specificity is greater than
      classical criteria of ischemia. The sensitivity of rSBP is poor for the diagnosis
      of single vessel disease, but of equal value compared to ST segment depression in
      the presence of multivessel disease, with no gender difference. The specificity
      of rSBP is higher than ST segment depression in women (p < 0.001) compared to men
      (p < 0.05). rSBP has a positive correlation with the number of coronary vessels
      diseased but not with the extent of ST segment depression. Our study demonstrates
      that rSBP at 3 minutes post-exercise is a less good diagnostic sign than the
      classical criteria of myocardial ischemia. However, rSBP has good specificity,
      particularly in women, thus reducing false positive tests related to ST segment
      depression. rSBP is also a marker of the severity of coronary artery disease.

PMID- 9561588
TI  - [Surgery of rectal carcinoma: 1997 status assessment].
AB  - The rectum and mesorectum are enclosed in a fascial sheath, the fascia propria,
      and represent an anatomical entity of abdominal origin. This package is a well
      known anatomical and oncological base for radical rectal cancer excision. It is
      at present under discussion again under new aspects: The surgical and oncological
      quality of rectal cancer excision is largely surgeon-dependent. Modern rectal
      surgery is refined, with sharp, very precise dissection respecting the relevant
      fascial planes, identifying and protecting the autonomous pelvic nerves and
      achieving radical locoregional tumor clearance, thus virtually eliminating the
      serious problem of pelvic recurrence. In this overview the concept of total
      mesorectal excision (TME) is explained and open questions are discussed. It
      remains to be determined whether a refined and anatomically precise operative
      technique or the oncologic concept of TME are of primary importance, and also
      whether patient selection influences the results to some degree.

PMID- 9561587
TI  - [Surgical treatment of severe emphysema: lung transplantation or volume
      reduction?].
AB  - In recent years, lung transplantation (LT) and volume reduction surgery (LVRS)
      have been proposed for selected patients with end-stage pulmonary emphysema.
      Retrospectively, we analyzed the perioperative time course of 30 patients with
      emphysema who underwent either LVRS (n = 17) or LT (n = 13). In the LVRS group,
      patients were significantly older, presented less severe functional disability
      and all but one could be extubated at the end of surgery. In contrast, patients
      undergoing LT required postoperative mechanical ventilation (19 +/- 11 hrs) and
      had a prolonged hospital stay (37 [25-60] days vs 19 [11-42] days in LVRS
      patients) due to reperfusion lung edema, infection, hemorrhage and acute
      rejection. Six months postoperatively, forced expiratory volume in 1 second was
      improved and was significantly larger after LT compared with LVRS (+200% vs
      +63%). Our preliminary results suggest that, although LT produces greater
      functional improvement, LVRS is associated with lower surgical risk and is an
      alternative therapy in selected patients with severe emphysema.

PMID- 9561589
TI  - [Blue diapers II].

PMID- 9561590
TI  - Health and the macro economy in a borderless world.

PMID- 9561591
TI  - Border malaria in Yunnan, China.
AB  - Yunnan Province, due its international borders with Myanmar, Vietnam and Lao PDR
      has a large number of imported cases of malaria, including a high proportion of
      Plasmodium falciparum, as a result of the mobility of the population. This
      movement is due to workers coming from other provinces where there is no malaria
      to work in the productive tropical lowlands. Chinese nationals who have gone to
      work in neighboring countries, border trade and refugees from Myanmar. Much of
      Yunnan is peopled by ethnic minorities living in remote mountainous and forested
      areas which are difficult to reach. However, surveillance has been strengthened
      by training 3,900 primary health care workers and combining the search for
      visiting foreigners, returning Chinese and people from other provinces with
      public security, customs formalities and employers. Any visitor detected by these
      services is obliged to have a blood slide taken. This has resulted in an earlier
      and more complete detection of malaria cases, reducing incidence from 19.19 to
      12.12/10,000 in the border area over the last 10 years. This is despite a
      considerable increase in population movement and the threat of drug resistant
      malaria.

PMID- 9561592
TI  - In vitro sensitivity of Plasmodium falciparum to eight antimalarials in China
      Myanmar and China-Lao PDR border areas.
AB  - In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of
      Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China
      Myanmar border areas were tested. The resistant rates of P. falciparum to
      chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates
      to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases
      were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the
      Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and
      arteether. Resistant rates from other areas were 0-11%. P. falciparum from China
      Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68
      88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on
      the China-Lao PDR border showed that the average defervescent time of falciparum
      malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during
      1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2%
      to 37.5%. The results monitored in vitro showed that all cases assessed in 1988
      for response to pyronaridine were sensitive, but 36.4% of cases had emerging
      resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results
      suggested that P. falciparum in these areas has expressed resistance to
      chloroquine and amodiaquine. However, the parasites are still sensitive to
      artemisinin, pyronaridine, mefloquine, quinine, but with a declining
      sensitivities.

PMID- 9561593
TI  - A comparative study of artesunate and artemether in combination with mefloquine
      on multidrug resistant falciparum malaria in eastern Thailand.
AB  - Plasmodium falciparum in Thailand is highly resistant to chloroquine, sulfadoxine
      pyrimethamine and there is increasing resistance to quinine and mefloquine. The
      use of qinghaosu derivatives alone or in combination with mefloquine has been
      shown successfully effective against multidrug resistant P. falciparum in many
      clinical trials. However their applications with ambulatory treatment should be
      assessed. 394 uncomplicated falciparum malaria cases studied at Trat and
      Chanthaburi malaria clinics, eastern Thailand, were allocated at random to
      receive either one of the seven following regimens: A) artesunate 600 mg over 2
      days and mefloquine 1,250 mg in divided doses. B) artemether 640 mg over 2 days
      and mefloquine 1,250 mg in divided doses. C) artesunate alone 700 mg over 5 days
      period. D) artemether alone 800 mg over 5 days period. E) quinine plus
      tetracycline for 7 days. F) mefloquine 1,250 mg in divided doses and G)
      artesunate 600 mg over 2 days period and mefloquine 750 mg. The follow-up was on
      Days 1, 2, 7, 14, 21 and 28. Patients tolerated all regimens very well and there
      was no serious side effects. The adverse effects did not differ among the seven
      regimens. The cure rates were 98.7, 97.1, 97.9, 96.7, 92.3, 100 and 95.2%,
      respectively. There was no significant difference of cure rates among various
      regimens. A total of 16 P. vivax and 1 P. malariae reinfections were reported
      among the study groups during the second half of the follow-up period, 14 of
      which were from the groups administered short action drugs (artesunate,
      artemether or quinine). The results suggested that either artesunate 600 mg or
      artemether 640 mg in combination with mefloquine 1,250 mg over a period of two
      days should be considered as alternative regimens for treating uncomplicated
      multi-drug resistant falciparum malaria.

PMID- 9561594
TI  - Effect of artemether on electrocardiogram in severe falciparum malaria.
AB  - The effect of intramuscular artemether (intramuscular loading dose of 160 mg,
      followed by 80 mg daily for another 6 doses), in comparison with that of quinine
      (intravenous infusion of loading dose of 20 mg/kg, followed by 10 mg/kg q 8
      hourly for 7 days), on the electrocardiograph of severe falciparum malaria
      patients were investigated in 102 Thai patients (92 males, 10 females) admitted
      to Pra Pokklao Hospital, Chantaburi, southeast of Thailand. Fifty patients (19
      with quinine and 31 with artemether) were eligible for ECG analysis. Hypotension
      was found significantly more common in the quinine group (13 vs 2 cases).
      Thirteen, 5 and 1 patients with quinine treatment, respectively, had tachycardia,
      non-specific T-wave change and QTc prolongation. No significant dysrhythmia was
      found despite high plasma quinine concentrations. Five patients died; their ECGs
      were not significantly different from those who survived. In the group with
      intramuscular artemether, 17 cases had tachycardia prior to artemether treatment.
      QTc prolongation and non-specific T-wave change were found in 2 and 6 cases. One
      patient had RBBB and second degree AV-block on Day 1, but returned to normal on
      Day 2. No other dysrhythmia or other significant changes in ECG tracing which
      would suggest any effect of artemether on cardiovascular system were observed.

PMID- 9561595
TI  - Phase II trial in China of a new, rapidly-acting and effective oral antimalarial,
      CGP 56697, for the treatment of Plasmodium falciparum malaria.
AB  - One hundred and two Chinese out-patients with naturally acquired, previously
      untreated, falciparum malaria were selected to evaluate the efficacy of a new
      combination anti-malaria therapy, CGP 56697 (artemether plus benflumetol). In
      this open non-comparative trial each patient received a combination of 80 mg
      artemether and 480 mg benflumetol given orally at 0, 8, 24 and 48 hours (total:
      320 mg artemether, 1,920 mg benflumetol). Patients were kept for 28 days in a
      transmission-free hospital in an area with chloroquine resistant falciparum
      malaria to prevent reinfection and to aid diagnosis of recrudescence. Progress
      and possible adverse effects were monitored by blood film parasitology, blood
      biochemistry assays, urinalysis, ECG and X-ray. Ninety-eight of the 102 patients
      were shown to be free of infection at 28 days, a 96.1% cure rate. Parasite
      reduction at 24 hours was 99.4%. Time to effect complete parasite clearance
      ranged from 24 to 54 hours (median 30 hours). Time for fever clearance ranged
      from 6 to 78 hours (median 18 hours). Recrudescence was low (3.9%). No
      significant adverse side-effects were encountered. It is concluded that CGP
      56697, a combination anti-malaria therapy of artemether with benflumetol, offered
      a rapid and highly effective treatment for acute uncomplicated falciparum malaria
      in an area of chloroquine-resistant malaria in China.

PMID- 9561596
TI  - Malaria in Honiara, Solomon Islands: reasons for presentation and human and
      environmental factors influencing prevalence.
AB  - During February and March 1995, out-patients attending health clinics and the
      Central Hospital in East Honiara, Guadalcanal, Solomon Islands, were surveyed
      with the aim of determining factors influencing the differing rates of malaria,
      the proportion of transmission occurring within the town, and the reasons for
      presentation. Three hundred and nine adult patients, who were sick and had blood
      smears taken, were asked about their general knowledge of malaria transmission.
      Of those interviewed, 120 were visited at their home in East Honiara, to
      determine variables. EpiInfo 5.1 was used in analysis. A history of fever alone
      was not a good indicator of parasitemia. Most precautions, including bed nets,
      window screens and personal precautions were of little benefit. Significant
      protection was afforded individuals and families with indoor kitchens. Patients
      not completing their antimalarial treatment fared worse in terms of parasitemia
      and malaria history. Most malaria/parasitemia was indigenous to Honiara. Many
      patients had a good knowledge of malaria transmission and mosquitos, but this did
      not translate into a lower rate of parasitemia or malaria.

PMID- 9561597
TI  - Killing of blood stage Plasmodium vinckei petteri by spleen macrophages through L
      arginine dependent mechanism.
AB  - A series of experiments was carried out to investigate the involvement of the L
      arginine-dependent effector mechanism (LADEM) in the killing of the blood stages
      of the rodent malaria parasite, Plasmodium vinckei petteri, by activated spleen
      macrophages in vitro. P.v.petteri-infected red blood cells were co-incubated with
      spleen macrophages from normal mice which had previously received 10(8)
      Mycobacterium bovis (BCG) 5 days earlier, in the presence of 0.1 microgram/ml LPS
      with and without 0.1 mM L-NMMA, an L-arginine analogue which inhibits LADEM, for
      16 hours. The viability of the parasites was assessed according to their
      infectivity following inoculation into experimental mice. Incubation of parasites
      with spleen macrophages in the presence of LPS without L-NMMA reduced the
      parasite viability to about 3%. When L-NMMA was included in the culture,
      inhibition of parasite killing was observed, resulting in an increase of parasite
      viability to about 21%. These data provide evidence to suggest that spleen
      macrophages play an important role as effector cells in the immune mechanisms
      against P.v.petteri infection, and that the parasite killing of these cells, at
      least in part, was mediated by LADEM.

PMID- 9561598
TI  - Experience of combined tetravalent diphtheria, tetanus, whole-cell pertussis and
      hepatitis B vaccine in Thailand.
AB  - In 1992, hepatitis B (HB) vaccination of all newborns was officially included in
      the national expanded program on immunization (EPI), since satisfactory levels of
      immunity had been attained among the target populations of Chiang Mai and Chon
      Buri Province during the trial period, 1989 and 1992. In order to facilitate this
      process and to reduce the administrative costs created by integration of the
      additional vaccine, the option of combining HB vaccine with the DTP vaccine was
      investigated. Thus, in 1991 our group performed a clinical study of Smith Kline
      Beecham Biological's DTP-HB vaccine, administering it to 160 infants of HBsAg
      negative mothers at the age of 2, 4 and 6 months, respectively. We found the
      evoked immune responses to be at least equal to, if not higher, than those
      achieved with the monovalent vaccine. Likewise, any adverse reactions were
      comparable to those observed after administering either DTP or HB vaccine
      separately. According to our additional data, we consider HB vaccination at
      birth, followed by the combined DTP-HB vaccine at the ages of 2, 4, 6 and 18
      months, respectively, most advantageous and we would recommend integrating this
      regimen into the basic immunization service. Thus, the possibility of eradicating
      hepatitis B infection altogether might eventually be provided.

PMID- 9561599
TI  - Urban-rural comparison of HBV and HCV infection prevalence among adult women in
      Shandong Province, China.
AB  - In order to make urban-rural comparison of the prevalence of hepatitis B and C
      virus (HBV and HCV, respectively) infection in China, a twin survey was conducted
      in 1996 on two groups (50 subjects each) of 21-55 year-old, apparently healthy
      women for infection markers and serum enzyme levels; one group (the urban group)
      was in Jinan, the provincial capital of Shandong Province, and the other (the
      rural group) was in a farming village in Zhangqiu area some 30 km away from Jinan
      City. Comparison between the two groups showed that there was no significant (p >
      0.10) difference in the prevalence of HBsAg+, anti-HBs+, anti-HBc+ and the cases
      positive to any of three HBV infection markers (i.e. HBV+). No age-dependent
      difference was detected within or between the groups. Thus the overall positivity
      rate was 8% for HBsAg+, 47% for anti-HBs+, 48% for anti-HBc+, and 64% for HBV+.
      No anti-HCV+ case was found either in the urban group or in the rural group.
      Liver function remained normal in all cases studied. The results together with
      perusal of published data suggest the urban-rural difference will not be
      remarkable, if present, in HBV and HCV infection in the regions studied, and
      possibly in China as a whole.

PMID- 9561600
TI  - Hepatitis C antibody prevalence and risk factors of some female sex workers in
      Thailand.
AB  - One high risk group for hepatitis C virus (HCV) infection is female sex workers
      (FSWs). A study of HCV antibody prevalence and group risk factors was conducted
      in 200 FSWs in Ratchaburi Province, Thailand, during June to December 1995. FSWs
      were interviewed and their blood specimens were collected for determining HCV
      antibody by second generation EIA (ABBOTT). After the laboratory results, the
      FSWs were divided into 2 groups, anti-HCV positive and anti-HCV negative. The
      variables obtained from interviews were analysed by X2-test and Odds Ratio.
      Prevalence of HCV antibody positives was 9.5%. It tended to be increased by the
      longer duration of working in the sex trade. The anti-HCV prevalence of FSWs
      working 9 years or more in the sex trade was significantly higher than that of
      FSWs working 4 years or less by about 3.5 times (23.08% vs 6.67%, p = 0.008). The
      anti-HCV positive FSWs had a higher percentage of anti-HIV positivity, but it was
      not of statistical significance (p = 0.078). The factors associated with high
      risk for HCV infection in this group were (a) Domicile (Northeast): OR = 3.07, (p
      = 0.0182), (b) Duration of working (> or = 4 years): OR = 3.13 (p = 0.0216), (c)
      Having a tattoo: OR = 4.12 (p = 0.0406), and (d) Having a history of STDs in the
      last 4 years: OR = 3.46 (p = 0.0165).

PMID- 9561601
TI  - Clients and brothel managers in Kramat Tunggak, Jakarta, Indonesia: interweaving
      qualitative with quantitative studies for planning STD/AIDS prevention programs.
AB  - Clients and brothel managers are often the most powerful decision-makers
      regarding condom use in brothels, but since publicly promoting condom use is
      still "culturally" difficult in Indonesia, the most feasible way of reaching
      clients is through the female commercial sex workers (FCSWs) and their managers.
      The existence of quasi-official brothel complexes in many major Indonesian
      cities, however, does make the government a key player in promoting condom use
      within these complexes. Interweaving qualitative with quantitative studies, this
      paper, which is part of a larger study, reveals the FCSWs' client/managers
      related determinants of condom use. Policies that will promote condom use in
      brothel complexes are critical to the prevention of the spread of HIV throughout
      this community, as well as from it to the greater community.

PMID- 9561602
TI  - Second report of AIDS related attitudes and sexual practices of the Jakarta Waria
      (male transvestites) in 1995.
AB  - As the second part of a community based educational campaign to convey the risk
      of HIV/AIDS to commercial sex workers in Jakarta, from May-July 1995, a total of
      253 male transvestites (WARIA) were questioned about their sexual behavior
      patterns and their knowledge and attitude toward HIV/AIDS. In the previous
      report, 1991-1993, there was one out of 830 WARIA found HIV positive in November
      1993. In this study, 1995, a total of two out of 253 WARIA were confirmed of HIV
      infection in July 1995. Most of them still have incorrect knowledge on HIV/AIDS
      transmission mode, they are still practicing high risk sexual attitudes such as
      an exchange partner rate of 5 men per three weeks, low condom use (1.2 out of the
      last 5 sexual contacts). The reasons for not using condoms were forgetfulness
      35.3% and partner does not like condom 38.2% Most of WARIA know about condoms
      (94.5%), but it is difficult to access condom use from small shops around them.
      Therefore, to prevent further spread of HIV/AIDS in WARIA, condom should be used
      constantly and properly. It has been shown from another study, that more
      information, better availability and better promotion of condoms can increase
      condom use. Thus, attention should be placed on various ways of distributing
      condoms for WARIA in Jakarta, especially community-based distribution by peer
      leaders, social marketing and commercial sales.

PMID- 9561603
TI  - Dengue surveillance in Metro Manila.
AB  - In a one-year surveillance of dengue infection in four hospitals in Metro Manila,
      Philippines, 143 patients were enrolled. Sixty seven were diagnosed by virus
      isolation and serology. Majority of patients had secondary antibody response.
      Only 5 patients developed dengue shock syndrome. Only dengue types 1 and type 2
      were isolated. Highest incidence occurred among older children and young adults.
      Thrombocytopenia and hemoconcentration were observed in 37% and 77% of patients,
      respectively. There was no fatality. Several problems were identified in the
      course of the study which need to be corrected in order to have good quality
      surveillance data in future undertakings.

PMID- 9561604
TI  - Kuru and "new variant" CJD.
AB  - Acquired transmissible spongiform encephalopathies in humans include Kuru (a
      disease which was associated with ritualistic cannibalism in Papua New Guinea),
      iatrogenic Creutzfeldt-Jakob disease and a newly recognized variant form of
      Creutzfeldt-Jakob disease (nvCJD). Clinical and neuropathological features of
      nvCJD are reminiscent of Kuru: early and progressive cerebellar ataxia and
      numerous characteristic Kuru-type amyloid plaques surrounded by spongiform
      change. In contrast to typical cases of sporadic CJD, Kuru and nvCJD affect young
      patients. The newly recognized form of CJD has been identified in ten young
      people in the UK in 1996, approximately 10 years after the beginning of the
      bovine spongiform encephalopathy (BSE) epidemic in the UK. Molecular analysis has
      shown that nvCJD has strain characteristics that are distinct from other types of
      CJD but similar to those of BSE. In the UK an estimated half a million BSE
      infected cows entered the human food chain before the bovine offal ban of 1989.
      To be effective the oral route probably requires high-infectivity titers which
      are encountered only in the brain, spinal cord and eyes of naturally infected
      cows. In patients with Kuru, titers of more than 10(8) infectious doses per gram
      were reported in the brain tissues. As a result of the estimated very long
      incubation period of nvCJD (10 to 30 years or more) the predicted nvCJD epidemic
      will have the shape of a normal distribution curve with a peak expected in 2009.
      The epidemic may extend until 2030. There is already an example to illustrate
      such a curve in its descending line: the decline of Kuru deaths following the
      interruption of ritual cannibalism.

PMID- 9561605
TI  - Use of polymerase chain reaction in the diagnosis of toxocariasis: an
      experimental study.
AB  - In this paper we report the usefulness of polymerase chain reaction technique in
      the diagnosis of visceral larva migrans in a mouse model. Liver samples obtained
      from two set of experimentally infected mice (10, 100, 1,000 and 10,000
      embryonated Toxocara canis eggs per mouse) along with the eggs of T. canis, T.
      cati and Ascaris suum were included in this study. Polymerase chain reaction
      (PCR) was performed using Toxocara primers (SB12). The first PCR product
      electrophoresis revealed very thin positive bands or no bands in liver samples.
      However, on second PCR a clear-cut bands were observed. No positive band was
      shown by A. suum eggs. Our findings thus indicate the usefulness of PCR technic
      in the diagnosis of visceral larva migrans (VLM) in liver biopsy materials
      specifically by means of double PCR using the primer SB12.

PMID- 9561606
TI  - The relationship between morbidity and intensity of Schistosoma japonicum
      infection of a community in Jiangxi Province, China.
AB  - Seven hundred and eighty-five individuals from an area endemic for Schistosoma
      japonicum had parasitological and physical examinations done. A morbidity
      questionnaire was also administered to each participant. Among those with S.
      japonicum infection, there was a significant increase in diarrhea, blood in the
      stool and weakness during the previous two weeks. The severity of the disease
      appears to be related to the history of schistosomiasis japonicum and these
      results give further justification for treatment of the infected individuals and
      those severe morbidity groups in community based chemotherapy programs designed
      to reduce morbidity in endemic areas.

PMID- 9561607
TI  - The impact of a decade long opisthorchiasis control program in northeastern
      Thailand.
AB  - Based on the figures obtained from a regional survey in 1981, the overall
      prevalence of opisthorchiasis in northeastern Thailand was as high as 34.6%.
      Traditional consumption of improperly cooked fish dishes and unhygienic
      defecating habits among rural inhabitants have been recognized as significant
      factors determining such high prevalence of this liver fluke in that area.
      Following experience of Mahidol University's Faculty of Tropical Medicine in
      Thailand of treating liver fluke infected individuals with praziquantel, the
      Ministry of Public Health started a liver fluke control program in the northeast
      as special service units in 1984 in 4 provinces. In 1988, the program was
      expanded to cover all 19 northeastern provinces, services being rendered at a
      community level covering stool examination and treatment of positive cases.
      Intensive health education was integrated as one element of liver fluke control
      program. During the early phase of operation (attack phase) a mobile stool
      examination team was the crucial strategy for active service. Following the
      attack phase, passive service was operated at each health service facility
      provided that results of population based program evaluation in each area showed
      a low prevalence according to the set target. Regionwide assessments in 1991 and
      1992 indicated a declining trend of prevalence from 34.6% to 30.19% and 24.01%,
      respectively. In 1994, a population-based sampling survey was carried out to
      measure the effect of the liver fluke control program over 10 years operation
      (1984-1994) on both behavioral outcomes and prevalence impact. Sample for the
      assessment of behavior were 1,268 individuals, while another 1,912 samples were
      used for determining disease prevalence. Health related behaviors regarding
      frequent consumption of uncooked fish dishes decreased from 14% in 1990 to 7% in
      1994 while occasional consumption remains as high as 42%. The prevalence of
      opisthorchiasis is 18.5% with a large variation in infection rate (5.20-56.25%).

PMID- 9561608
TI  - Imported cutaneous leishmaniasis in Thailand.
AB  - Eleven cases of imported cutaneous leishmaniasis are described based on clinical
      features such as sex, age, occupation, country visited prior to consultation,
      sites and numbers of lesions, duration of illness, treatment and outcomes.
      Ketoconazole was shown to be effective against imported cutaneous leishmaniasis.
      With the increasing numbers of cutaneous leishmaniasis due to exchange workers
      going to the endemic areas and the presence of vectors in some localities in
      Thailand, primary transmission of the disease in this country is possible if
      feeding habits of the vectors change.

PMID- 9561609
TI  - Efficacy of single dose albendazole on the prevalence and intensity of infection
      of soil-transmitted helminths in Orang Asli children in Malaysia.
AB  - The efficacy of a single-dose 400 mg albendazole to treat Ascaris, Trichuris and
      hookworm infection was studied in Orang Asli community. Kato-Katz examination was
      performed on fecal samples which were collected before treatment, 1 and 4 months
      after treatment. A total of 123 children were involved in all three surveys. The
      cure rate of Ascaris infection was 97.4% and the egg reduction after treatment
      was 99.9%. The cure rate for hookworm infection was 93.1% with 96.6% egg
      reduction. Although the cure rate was low in Trichuris infection (5.5%), egg
      reduction was more evident (49.1%). The reinfection rate at 4 months after
      treatment was 54.5%, 3.6% and 10.3% for Ascaris, Trichuris and hookworm
      infection, respectively. Within 4 months after treatment almost one-fifth
      children with Ascaris and hookworm infection reached pre-treatment intensity
      infection. In Trichuris infection, however more than half of the children reached
      their pre-treatment intensity infection at 4 months after treatment. Findings
      suggest that 4-monthly targeted periodic treatment with 400 mg single-dose
      albendazole in highly endemic areas can have a significant impact on intensity
      infection of Ascaris and hookworm, but not on Trichuris infection.

PMID- 9561610
TI  - Clonning and sequence analysis of the 26 kDa glutathiones-transferase gene of
      Schistosoma mekongi.
AB  - The number of genomic DNA or cDNA sequences of Schistosoma mekongi accessible in
      Genbank or EMBL is very limited up to now. Recently, two reports have appeared on
      the molecular phylogeny of Schistosoma species inferred from partial sequence
      data of rRNA genes; no further sequence data of S. mekongi is available yet.
      Knowledge of the molecular structure of protein coding genes of S. mekongi will
      provide a better understanding of gene function in the genus Schistosoma. A cDNA
      library of S. mekongi adult male was constructed and a cDNA encoding the 26 kDa
      glutathione S-transferase protein of this species was cloned. Sequence analysis
      of this cDNA confirmed the close phylogenetic relationship of S. mekongi to S.
      japonicum.

PMID- 9561611
TI  - The effects of temperature, light and water upon the hatching of the ova of
      Schistosoma japonicum.
AB  - Eggs of Schistosoma japonicum were obtained from infected patients' feces from
      Yujiang City, China to observe the effects of temperature, light and water on the
      hatching of eggs. The temperature of water and light played important roles on
      the hatching of S. japonicum, but the type of water did not. A constant
      temperature of 28 degrees C and electrical light produced the highest rate of
      hatching, and reproducible results, whereas a temperature of 4 degrees C or 37
      degrees C, and the absence of light inhabited the hatching of eggs. The
      percentage of eggs hatched during the first 8 hours of 24 hours incubation was
      94.90%, so that using the hatching rate of the first 8 hours could approximate
      the total hatching rate of samples.

PMID- 9561612
TI  - Schistosoma mansoni: relocation of parasites to lungs from hepatic portal system
      in rodents.
AB  - The prevalence and development of adult worms in the lungs of mice and gerbils
      infected with Schistosoma mansoni was investigated. All infected BALB/c mice
      harbored the schistosomes in their lungs at 10-12 weeks post-infection, showing
      the distinct relocation of adult worms to the lungs, from the hepatic portal
      system. The male and female flukes from lungs of BALB/c mice were significantly
      smaller than those from livers. The percentage of gravid females in lungs was
      considerably lower than that in the livers. The number of eggs recovered from
      lungs of BALB/c mice and gerbils having lung female worms, however, was higher
      than that from animals without lung females, indicating egg deposition of lung
      females. The number of eggs detected in the brains correlated well with the
      number of eggs from the lungs in BALB/c and ICR mice. Out of 119 infected gerbils
      at 8 weeks post-infection, only two animals had egg-emboli in the brain vessels,
      although many eggs embolized in the lungs of those animals. These data suggest
      that transfer of worms to the lungs from livers involves reduction of worm
      recovery from the portal circulation, and also pulmonary pathology of the
      disease.

PMID- 9561613
TI  - Longitudinal surveillance after filariasis control in Guangdong Province, China.
AB  - This paper reports the longitudinal surveillance with epidemiology, entomology
      and serology after filariasis has been controlled. The results showed that the
      microfilarial rate, natural infection rate of vectors and the positive rate of
      filarial antibodies decreased year by year.

PMID- 9561614
TI  - Evaluation of Bithynia funiculata snail antigens by ELISA-serodiagnosis of human
      opisthorchiasis.
AB  - Four batches of crude somatic antigens from: (1) Opisthorchis viverrini adult
      worms, (2) Bithynia funiculata-whole body, (3) B. funiculata-head-foot, and (4)
      B. funiculata-visceral mass were assayed against sera from 81 opisthorchiasis
      patients, 30 parasite-free healthy individuals, and 50 individuals infected with
      other helminthic infections, and their antibody levels determined. By IgG-ELISA,
      the antigenic reactive proteins were found in both the head-foot and the visceral
      mass of B. funiculata snails, but the whole snail antigens gave the best results.
      Furthermore, it was as good as when O. viverini antigens were used. Antibody
      levels of sera from patients with opisthorchiasis assayed against antigens from
      whole B. funiculata snails were significantly higher than those of the other two
      groups. The cut-off value for positivity at 0.228 gave 80.2% sensitivity and
      81.2% specificity. Cross reactions were observed with sera from patients with
      paragonimiasis and strongyloidiasis. No cross reactions were found to occur with
      sera from healthy individuals.

PMID- 9561615
TI  - Malaria and Anopheles mosquitos in Malaysia.
AB  - Until today, malaria is still one of the most important diseases in Malaysia.
      This is because Malaysia is located within the equatorial zone with high
      temperatures and humidities, usually important for the transmission of malaria.
      The number of malaria cases were estimated to be around 300,000 before the
      launching of the Malaria Eradication Program (MEP). The program was successful in
      reducing the numbers progressively during the 1967-1982 period. During the period
      1980-1991, the highest number of malaria cases recorded for the country was
      65,283 in 1989 (16,902 in Peninsular Malaysia, 47,545 in Sabah and 836 in
      Sarawak) whilst the lowest was 22,218 (10,069 in Peninsular Malaysia, 11,290 in
      Sabah and 859 in Sarawak) in 1983. In Malaysia, there are 434 species of
      mosquitos, representing 20 genera. Of these, 75 species are Anopheles that
      comprise of 2 subgenus, i.e. Anopheles and Cellia. Of the 75 species, only 9 have
      been reported as vectors: An. maculatus, An balabacensis, An. dirus, An. letifer
      An. campestris, An. sundaicus, An. donaldi, An. leucophyrus and An. flavirostris.
      The behavior, seasonal abundance, biting activities and breeding sites of these
      species are discussed.

PMID- 9561616
TI  - Residual efficacy of deltamethrin 2.5 wp (K-othrin) sprayed on different types of
      surfaces against malaria vector Anopheles culicifacies.
AB  - Residual efficacy of deltamethrin 2.5 wp on various types of surfaces was tested
      against Anopheles culicifacies under field conditions using WHO standard
      procedure. Deltamethrin was most effective on the thatched surface and produced
      100% mortality of An. culicifacies adults up to 12 weeks, even when exposed at
      the lowest dose /12.5 mg/m2. It was least effective on brick surface and 100%
      mortality was observed only for three weeks. The efficacy was observed for 8 and
      7 weeks on mud and cement surfaces, respectively. However, at the higher rate of
      application, i.e. 25 mg/m2, 100% mortality of this species was obtained for 12,
      10, 9 and 12 weeks on mud, cement, brick and thatch surfaces, respectively.

PMID- 9561617
TI  - Breeding and day resting habitats of Anopheles dirus in Assam, India.
AB  - Longitudinal surveys at monthly frequency were carried out during 1995-1996 in a
      forest fringed village of district Dibrugarh, Assam to decipher the breeding and
      day resting habitats of Anopheles dirus. It regularly bred in small, shallow,
      rain filled, transient, shady or partly shady puddles/ground pools in the rainy
      months and in the perinneal streams in the adjoining forest of the village during
      dry months. In pools, the degree of interspecific association (0.238 +/- 0.174)
      and index of association (0.428) of An. dirus breeding was highest with Aedes
      caecus. An. dirus was completely exophilic and rested during day time in the
      forest mostly on tree trunks upto the height of 4-5 feet from the ground in dark
      moist niches avoiding direct sun light.

PMID- 9561618
TI  - Collection of anopheline mosquitos in three villages endemic for malaria in
      Khammouane, Lao PDR.
AB  - Anopheline mosquito collections were made during the months of May and June (dry
      season) and August (rainy season), 1996 at villages, Nakham, Namdik and Hinboon
      Neua in Khammouane Province. Larval collections were also made in 3 slow running
      streams around Nakham villages in May 1996. Altogether, 3,549 adult females
      consisting 19 Anopheles species were collected by 3 nights of human and 6 animal
      bait traps and 3 resting collections. Among them, Anopheles vagus (19.75%), An.
      philippinensis (15.02%), An. nivipes (11.55%), An. pallidus (11.27%), An.
      peditaeniatus (8.34%), An. kochi (8.00%) and An. barbirostris (7.27%) were
      predominant species. The immatures of An. barbirostris, An. minimus, An.
      maculatus sensu lato, and An. culicifacies were found in the streams of Nakham.
      It is noteworthy that An. minimus, An. dirus and An. maculatus sensu lato, which
      are well known malaria vectors in Thailand, were recorded for the first time in
      this area.

PMID- 9561619
TI  - A dot-ELISA test using monoclonal antibody-purified antigens for the diagnosis of
      paragonimiasis caused by Paragonimus heterotremus.
AB  - A dot enzyme-linked immunosorbent assay (dot-ELISA) using antigens purified by
      monoclonal antibody-affinity chromatography was developed for detecting
      antibodies to Paragonimus heterotremus in four groups of subjects. They consisted
      of 30 patients with P. heterotremus infection, 93 patients with other parasitic
      infections, 18 patients with pulmonary tuberculosis and 30 normal, healthy
      controls. Sensitivity, specificity, as well as positive and negative predictive
      values of the test were 100, 97, 88, and 100%, respectively.

PMID- 9561621
TI  - Detection of carrier status of hemophilia B using DNA markers.
AB  - Hemophilia B is an X-linked recessive disorder of the hemostasis involving a
      defective clotting factor IX. Amplification of the regions containing restriction
      fragment length polymorphisms (RFLP) can be achieved by the use of polymerase
      chain reaction (PCR). This paper describes the analysis of 2 RFLPs involving the
      Dde1 and Taq1 restriction sites within the factor IX gene in a family with
      hemophilia B. Digestion of the PCR products with Taq1 revealed a 163bp fragment
      in all the family members. This finding suggests the absence of restriction site
      for Taq1 enzyme. However, the Dde1 digest results in bands 369bp and 319bp
      segregated amongst the family members. The pattern of inheritance of the 369bp
      fragment in this family suggested that both the patient's mother and aunt are not
      carriers and that the patient's factor IX gene could have undergone a de novo
      mutation producing a defective factor IX gene responsible for the hemophilia B.
      This is supported by the fact that no family history of hemophilia B is indicated
      in the other male members within the family.

PMID- 9561620
TI  - Detection of circulating antigens of Parastrongylus cantonensis in human sera by
      dot-blot ELISA and sandwich ELISA using monoclonal antibody.
AB  - A dot-blot ELISA was compared with a previously performed sandwich ELISA for the
      detection of Parastrongylus cantonensis antigens in sera from patients. Using the
      same monoclonal antibody and the same sera, 6 of 10 sera (60%) from
      parastronglyiasis patients were positive in dot-blot ELISA, whereas with sandwich
      ELISA, 5 of the same patient sera (50%) were positive. The specificity in both
      assays was 100% using 50 sera from patients with other parasitic diseases; of
      these, 10 each were from patients with cysticercosis, filariasis,
      gnathostomiasis, malaria and toxocariasis. The control group consisted of 53 sera
      from normal health Thais and Malaysians. The sensitivity of the assays was,
      however, slightly better with dot-blot ELISA and because it is simple, quick and
      cost-effective, it may be a test of choice for specific diagnosis of human
      parastrongyliasis.

PMID- 9561622
TI  - The significance of HER-2/neu/c-erbB-2 gene amplification in benign and malignant
      breast disease.
AB  - This study was carried out to investigate the amplification of HER-2/neu oncogene
      in 66 patients with primary breast cancer and 90 samples from benign breast
      disease (BBD). The amplification of HER-2/neu oncogene in the DNA of paraffin
      embedded specimens was determined by differential PCR. Nineteen out of 66 (28.8%)
      breast cancer patients showed amplification of the gene. No gene amplification
      was found in benign breast disease. There was no significant correlation of HER
      2/neu amplification with, age, menopausal status, the number of positive nodes,
      tumor size, estrogen receptor, however, amplification of HER-2/neu gene was
      strongly correlated with nodal status (p = 0.0049). In node positive patients,
      the incidence of HER-2/neu amplification was high (43%). These findings indicate
      that the amplification of HER-2/neu gene may be of pathogenetic significance in
      breast cancer and may have a poor prognosis in node positive breast cancer
      patients while no gene amplification in benign breast disease suggests that HER
      2/neu amplification is a late molecular alteration event in the pathogenesis of
      breast cancer.

PMID- 9561623
TI  - Renal stones in Kelantan, Malaysia--has the pattern changed?
AB  - Records of 183 patients with renal stones managed at Hospital Universiti Sains
      Malaysia between 1985 and 1995 were retrospectively evaluated. The commonest
      symptom was lumbar pain which may be associated with either frequency, blood
      stained urine or dysuria. One hundred and sixty-one patients (88%) had upper
      tract stones while the remainder had lower tract stones. Positive urine cultures
      were seen in 33 patients. The commonest organism isolated was Escherichia coli
      followed by Klebsiella aeruginosa and Staphylococcus aureus. Almost all of our
      patients had renal impairment at presentation and 70% of them progressed to
      chronic renal failure. In contrast to previous findings, the pattern of renal
      stone in this region is similar to that described in Western society. Its effect
      on renal function is serious and hence warrant special attention.

PMID- 9561624
TI  - A comparative study of nutrition and health of mothers in Japan and the
      Philippines.
AB  - When comparing nutrition and health among mothers in both Japan and Philippines,
      it can be concluded that, in regard to nutrition, the results of the total
      dietary scores for mothers in divided into pregnant and after-delivery stages
      showed that pregnant Filipino mothers' average are lower than those of pregnant
      Japanese mothers. Pregnant Filipino mothers and those just after delivery to 4
      months had lower average dietary scores than Filipino mothers 5 months and later
      after delivery. These results are thought to be an important factor in the
      improvement of health condition and life expectancy of Filipino mothers and their
      children. In Japanese mothers, such differences were not found. When comparing
      individual dietary scores and the rate of nutrients consumed to the optimum
      amounts, significant differences were found among mothers in both countries.
      Analysis of food diaries of mothers from both countries found that Japanese
      mothers had average intakes of nutrients such as energy, protein, fat, vitamin B1
      and vitamin B2 and were deficient in calcium, iron and vitamin A. Filipino
      mothers took in average amounts of protein, calcium, iron, vitamin B2 and vitamin
      C and were deficient in energy, fat and vitamin B1.

PMID- 9561625
TI  - Russell's viper venom fractions and nephrotoxicity.
AB  - Apparently healthy Wistar rats of body weight 250-300 g were chosen for the
      experiments. A group of 6 rats were assigned for each fraction. The dose of
      Russell's viper venom (RVV) fraction used for in vivo experiments was 0.75
      microgram/g body weight. Of each batch of 6 rats 3 were sacrificed on the third
      day and the remaining 3 on the fifth day after the administration of test venom
      fractions. Daily urine output with proteinuria and serum creatinine were
      determined on the day they were sacrificed. Kidneys from the rats were also
      examined under light microscopy after hematoxylin and eosin staining. In the in
      vitro experiment, kidney slices (1 mm thickness) from normal rat was incubated
      with RVV fractions of 5 mg/ml concentration. The predominant renal lesions
      observed in both sets of animal experiments were tubular degeneration and
      necrosis. The changes were mostly confined to proximal tubules. Glomerular
      changes were mild. Similar tubulotoxic effects were produced by whole RVV as well
      as single fractions. Therefore, it is possible that RVV contains a common
      nephrotoxic (protein) component which is present in all fractions of the venom.
      The renal damage caused by RVV seemed to be due to both systemic effects (mainly
      DIC and renal ischemia) and direct tubulotoxic effects of the venom.

PMID- 9561626
TI  - Effect of sublethal dosages of malathion on the oral susceptibility of Aedes
      aegypti to dengue-2 virus infection.

PMID- 9561627
TI  - Antibodies to Orientia tsutsugamushi in soldiers in northeastern Thailand.
AB  - The prevalence and incidence of antibodies to Orientia tsutsugamushi, the
      etiologic agent of scrub typhus, in Thai soldiers living and working near the
      Thai-Cambodian border in Si Sa Ket Province was investigated. The point
      prevalence of antibodies varied from 0 to 4.1%. The incidence of antibodies,
      calculated from individuals who seroconverted following a negative result in a
      previous bleeding 3 to 5 months earlier, was 4.21% (9/214) in January 1992, 0 in
      April 1992 and 3.76% (8/213) in September 1992. An annual infection rate of 2.66%
      was estimated.

PMID- 9561628
TI  - Edwardsiella tarda bacteremia and septic arthritis in a patient with diabetes
      mellitus.
AB  - Edwardsiella tarda is an uncommon pathogen in the family Enterobacteriaceae which
      usually infects patients with underlying diseases. Its habitats include fresh
      water, a variety of animals and human feces. We report a case of E. tarda
      bacteremia and septic arthritis with underlying diabetes mellitus, the first
      found in Thailand.

PMID- 9561629
TI  - Four misdiagnosed cases of visceral bleeding caused by Haemadipha japonica.

PMID- 9561630
TI  - The portents and the promise of science for health.

PMID- 9561631
TI  - Human genome mapping: implications for health.

PMID- 9561633
TI  - Human genomics: implications for health.
AB  - Human genome research which tries to map and sequence all the 3 billion
      nucleotides in the entire DNA is progressing rapidly. Completion of the human
      genome sequencing is expected before the year 2005. Human genes, totalling 50,000
      100,000, will be identified, allowing the complete set of proteins--'the
      proteome' to be known. This together with genomic research in other species will
      lead to complete understanding of life at the molecular level and also its
      evolutionary history of 3,500 million years. Genomics will bring about a
      revolution in biology and health, because it is equivalent to having a
      'Biological Periodic Table' which is a foundation for understanding life, health,
      disease and for deriving of new tools for diagnosis, treatment, prognosis and
      prevention. Human genomics will give rise to Predictive--Preventive Medicine and
      Precision Medicine. It will have profound social implications. Preparation for
      the future is needed for societies to cope with and make proper use of the
      tremendous changes to be brought about by genomics.

PMID- 9561632
TI  - Human molecular genetics research at the International Centre for Genetic
      Engineering and Biotechnology.
AB  - The ICGEB started its activity in 1987 as a special project of UNIDO (United
      Nations Industrial Development Organization) and operates now as a fully
      autonomous International Organization, of which 40 countries are members at
      present. The mandate of ICGEB is to become a Centre of excellence for research
      and training in modern biology addressed to the needs of the developing world.
      The ICGEB consists of two main laboratories, one in Trieste (where the direction
      of the Centre is also located) and one in New Delhi, plus a network of 30
      Affiliated Centres. The Centre operates through: 1) specific research programs of
      hish scientific content at the Trieste and New Delhi laboratories; 2) long term
      training through post-doctoral and pre-doctoral fellowships; 3) short term
      training; 4) collaborative research program, through which the Centre finances
      research projects of major impact to the need of the Member States; 5) scientific
      services, namely consultation for scientific programs, distribution of reagents
      and a bioinformatics network particularly geared to the human genome research.
      The research on human molecular genetics in particularly active in the Trieste
      Component and concerns the study at the molecular level of several genes
      important for human health: control of DNA replication, response to infectious
      diseases, cardiocirculatory diseases, cystic fibrosis and cancer. The
      methodologies for developing new diagnostic methods and for developing gene
      therapy protocols are actively pursued. Through these programs, the member
      countries have access to state-of-the-art technologies anf know-how essential for
      the development of the molecular approaches to medicine brought forward by the
      study of the human genome.

PMID- 9561634
TI  - Human genome mapping and its medical perspectives.

PMID- 9561635
TI  - An overview of nutrition and development.

PMID- 9561636
TI  - Nutritional deficiencies and subsequent effects on mental and behavioral
      development in children.
AB  - Nutritional deficiencies at all stages of growth, both pre- and post-natal, can
      affect a child's physical, mental and behavioral development. In this paper, we
      review literature about how mental development is affected by the following
      nutritional conditions: low birth weight, mild, moderate, and severe protein
      energy malnutrition, iodine deficiency, and iron deficiency.

PMID- 9561637
TI  - Daily and weekly iron supplementation and physical growth of school age
      Indonesian children.
AB  - OBJECTIVE: To investigate the effect of 3 months iron supplementation on physical
      growth among anemic school children given daily and weekly and to know the
      response based on hemoglobin level. SUBJECT: One hundred forty-four children were
      measured for height, weight and hemoglobin level. Ninety seven children were
      anemic (67.36%) with Hb level < 12 g/dl and forty seven children were non anemic.
      anemic children were divided into 2 subgroups and randomly assigned to either
      daily and weekly Fe treatment for 12 weeks. The non anemic group were treated
      with weekly iron supplementation, which was accepted by the parents. OUTCOME
      MEASURES: Children's height, weight, and hemoglobin of T1 and T2 food recall
      method was used to know calorie, protein, vitamin C and iron intake in both daily
      and weekly subgroups. Three days food recall was performed in the second and
      third months by a nutritionist. RESULT: After iron supplementation, the
      hemoglobin level in both group increased significantly. The average change of
      hemoglobin between the 2 groups gave no significant difference. W/A and H/A after
      iron supplementation showed significantly increased in both groups. The average
      change of W/A and H/A between the 2 groups gave no significant difference.
      CONCLUSION: Daily and weekly iron supplementation showed no significant
      difference in increasing of hemoglobin level and physical growth. Further
      research must be done with appropriate sample size and well design.

PMID- 9561638
TI  - The devastating consequence of iodine deficiency.
AB  - Endemic cretinism is the most striking consequence of iodine deficiency. Although
      cretinism is a serious condition, it usually involves only about 5% of the
      population even in serious endemic areas. There is a spectrum between cretinism
      and normality, many are able to perform simple work and look apparently normal,
      but it is difficult for them to perform skilled labor. Studies in China using the
      IQ distribution curve revealed that every person in an endemic area lost about 10
      15 IQ points, so that the socio-economic development of the community was
      severely affected.

PMID- 9561639
TI  - Nutrition and development: other micronutrients' effect on growth and cognition.
AB  - Previous studies have provided strong evidence that protein-energy malnutrition,
      deficiencies of iron and iodine early on in life led to compromised growth and
      cognitive functions in young children. Recently, a growing body of knowledge
      indicated that other micronutrients also play a role in young child development.
      Severe as well as marginal vitamin A efficiency were shown to lead to an
      increased risk of morbidity and mortality in children. A meta-analysis of vitamin
      A intervention trials indicated an overall reduction of 23% in all-cause
      mortality rate. Delayed growth, especially stunting, was reported in children
      with clinical signs of vitamin A deficiency. In addition, deficiency of zinc,
      which is essential for DNA and protein synthesis, leads to growth failure and
      delayed secondary sexual maturation in man and animals. Preterm infants appear to
      benefit from zinc administration in terms of growth and development.
      Supplementation studies in infants and older children revealed that those who
      manifested overt zinc deficiency through either clinical or biochemical
      indicators showed an improvement in linear growth and occasionally, an increase
      in weight gain. Zinc may also play a major role in brain function based on strong
      evidence from experimental animals. Zinc deficiency gestation in mice, rats,
      rhesus monkeys caused impaired learning, reduced attention and poor memory in
      their offspring. Data in humans are few and inconclusive. With respect to brain
      function alone, other nutrients such as docosahexaenoic acid (DHA, 22:6 n-3 fatty
      acid) improve visual acuity and mental development in small-for-gestational-age
      infants, folate supplementation during pregnancy prevents neural tube defect in
      infants, selenium deficiency in animals affects activities of brain enzymes
      necessary for brain development and function. Although evidence is accumulating
      that micronutrients other than iron and iodine may be important for physical
      growth and brain development in young children, more well-controlled studies in
      humans are needed. Critical issues to be considered include: single vs multiple
      limiting nutrients, critical period of deficiency, responsive indicators and
      variables that may affect the results as environmental, psychological and social
      factors.

PMID- 9561640
TI  - New era challenges in nutrition.

PMID- 9561641
TI  - Promotion of healthy aging.

PMID- 9561642
TI  - Factors affecting longevity.
AB  - In view of the fact that hypercholesterolemia occurs in 31.4%, hypertension in
      16.7% and the smoking rate is 58.8% in males (Table 8), risk factors are not low.
      Despite this, we Japanese preserve a leading position regarding longevity. I hope
      that I have provided some evidence supporting the proposal that apparently not
      only a low fat intake but other factors including genetic make up and a
      relatively high antioxidant intake contribute to our longevity.

PMID- 9561643
TI  - Global assessment of nutrition risk factors in the elderly.
AB  - Global assessment of nutrition risk factors in the elderly consists of subject's
      history, physical examination, and laboratory tests, which are the indispensable
      mode to establish definite nutritional disorders. This is illustrated in a study
      of 150 free-living elderly Thais participating in the Global Assessment of
      Nutritional Risk Factors in the Thai Elderly. They consisted of 50 men and 100
      women, aged 60-86 years and were an affluent urban population. Diet-related
      chronic diseases including overall obesity, abdominal obesity, dyslipidemia,
      impaired glucose tolerance, diabetes mellitus, and hypertension were the major
      nutritional problems affecting their life and well-being. Thus appropriate
      nutritional intervention must be provided to improve their impaired health
      status.

PMID- 9561644
TI  - Aging, food, culture and health.
AB  - International comparison of food intake and health studies amongst the aged is
      providing new insight into the importance of food culture in social context for
      healthy aging. At same time the possible variance in eating behavior compatible
      with good health requires consideration. The IUNS (International Union of
      Nutritional Sciences) FHILL (Food Habits in Later Life) Project, comprises (1) a
      morbidity study on about 2,000 elderly in 13 communities (now available on CD
      Rom) and (2) a mortality follow-up study. In the morbidity study, a total health
      assessment score or Later Life Status Score (LLSS) has been considered in
      relation to non-nutritional and nutritional factors. The elderly Greek cohorts
      aged 70+ in Melbourne. Australia (M = 94, F = 95) and Spata, Greece (M = 51, F =
      53) have been used as a model for multivariate analyses to determine separately
      the importance of non-nutritional (well-being, memory, general health, medication
      use, activities of daily living, exercise, social activity and social networks
      scores) and nutritional variables (intake of food groups g/day, food group
      variety scores, nutrients) in accounting for LLSS. A mortality follow-up study on
      the elderly cohort in Spata, Greece has also been completed and published. The
      findings from these preliminary analyses on the Greek cohorts will be reviewed as
      an example of how food culture may be influencing both quality of life and
      survival in Greek elderly. The most important non-nutritional determinants of
      LLSS in Greeks included: mobility and independence (exercise and activities of
      daily living), well-being and memory (collectively explained 80% of the variation
      of LLSS). For nutritional variables, a high intake and variety of plant foods (in
      particular vegetables, legumes and fruit); a high intake and variety of seafood
      and a low intake of meat emerged with statistical and biological significance.
      Results from the mortality study also agree with findings from the morbidity
      study--particularly the importance of the overall traditional greek food culture,
      with its emphasis on plant derived food of various kinds, as opposed to
      individual food categories, in protecting against premature death. Strategies are
      advanced which may optimise nutritionally related health problems amongst the
      aged around the globe.

PMID- 9561645
TI  - Nutrition and chronic diseases--Indian experience.
AB  - Socio-economic changes are taking place all over the world, especially in
      developing countries, and these influence all aspects of life an all age periods.
      Resultant disparities have brought about alarming and increasing manifestations
      of malnutrition and non-communicable disease. Illiteracy, poor health facilities
      have damaging effects on children. Raising the literacy of girls and adolescents
      will reduce the leading cause of malnutrition in children, since these future,
      better educated mothers will be responsible for the children's welfare: child
      care status with mother care. Protein calorie sufficiency is only present in
      approximately 60% of the rural population of India: the remainder has differing
      degrees of malnutrition. When they move into better socio-economic status people
      are at increased risk from coronary heart disease and diabetes mellitus, for
      which several theoretical explanations have been proposed. There is a difference
      in the patterns of these diseases in urban and rural populations, the exact basis
      for which is not yet clear. For example, in the 25-64 years age group, coronary
      heart disease prevalence in Delhi is 97/1,000 while in a rural area it is
      27/1,000, while the respective figures for hypertension are 127/1,000 and
      29/1,000. The patterns in both groups have changed within 3-5 years. The
      geriatric age group has its own, changing features, due to increasing longevity
      of life, and to break up of social customs and family structure.

PMID- 9561646
TI  - Control and prevention of infectious diseases.

PMID- 9561647
TI  - Vaccines for the world: major challenges for the future.
AB  - Vaccination is at a turning point. The global use of usual infant vaccines has
      led to a remarkable decrease in disease burden associated with measles, pertussis
      or diphtheria while rapid progress is being made towards eradication of
      poliomyelitis through mass immunization campaigns. However, new disease targets
      are now emerging and research priorities, at a global level, encompass the
      development of a series of new vaccines. Recent technological advances have made
      this possible but the challenge of universal immunization is likely to require
      particular approaches. For example, it will be essential, in the near future, to
      define optimal ways to use the capacity of the immune system to generate long
      lasting protective responses against intra-cellular microorganisms, to develop
      vaccines efficient soon after birth and to devise new systems to simplify
      immunization. It will also be a real economic challenge to ensure that the new
      vaccines will become available for those who are at the highest risk, usually in
      the least developed countries.

PMID- 9561648
TI  - The human immunodeficiency virus (HIV) as a newly evolving pathogen.

PMID- 9561649
TI  - Concepts of control of Japanese encephalitis and dengue.
AB  - Japanese encephalitis and dengue are mosquito-borne virus diseases of major human
      disease importance to the Asian region. Our current knowledge of their
      distribution and transmission cycles is reviewed, the classical approaches to
      their control are discussed. The development of live attenuated vaccines for both
      disease offers possible elimination of human epidemics through combined use of
      vaccine and mosquito control.

PMID- 9561650
TI  - Elements of science and technology in the control and prevention of infectious
      diseases.

PMID- 9561651
TI  - Reproductive health.

PMID- 9561652
TI  - Prospects for fertility regulation.

PMID- 9561654
TI  - Sexual and reproductive health: an IPPF approach.

PMID- 9561653
TI  - Maternal mortality and safe motherhood.

PMID- 9561655
TI  - Meeting the health research challenges of the 21st century.

PMID- 9561656
TI  - Responding to challenges in health reform: new opportunities for the medical
      profession and medical schools.

PMID- 9561657
TI  - Global health in transition: pursuing human rights and equity in a changing
      world.

PMID- 9561658
TI  - Economics of health reform in East Asia.

PMID- 9561660
TI  - Science and Health: Opportunities and Challenges for the 21th Century. Human
      genome mapping: implications for health. Report of Working Group 1.

PMID- 9561659
TI  - Challenges for health in 21st century: building partnership for a knowledge based
      health system towards equity, quality and efficiency.

PMID- 9561661
TI  - Science and Health: Opportunities and Challenges for the 21th Century. Nutrition
      and development. Report of Working Group 2.

PMID- 9561663
TI  - Science and Health: Opportunities and Challenges for the 21th Century. Control
      and prevention of infectious diseases: emerging and re-emerging. Report of
      Working Group 4.

PMID- 9561662
TI  - Science and Health: Opportunities and Challenges for the 21th Century. Promotion
      of healthy aging. Report of Working Group 3.

PMID- 9561664
TI  - Science and Health: Opportunities and Challenges for the 21th Century.
      Reproductive health. Report of Working Group 5.

PMID- 9561665
TI  - Meeting the challenges of the 21st century through medical education, health
      research and health sector reform. Report of Working Group 6.

PMID- 9561666
TI  - Fertility levels, trends, and differentials in sub-Saharan Africa in the 1980s
      and 1990s.
AB  - This study presents an assessment of fertility trends in 23 countries of sub
      Saharan Africa. It examines trends and differentials in proximate determinants
      and fertility preferences. Findings from the Demographic and Health Surveys for
      these countries over a period of 15 years show that desired family size has
      decreased significantly. Two-thirds of the countries examined show evidence of
      fertility decline, a particularly rapid decline in the cases of Kenya and
      Zimbabwe. Areas with higher education for women and lower child mortality
      experienced larger reductions in fertility and desired family size. Contraceptive
      use far exceeds other proximate determinants in explaining these changes. The
      striking regularity in fertility reduction across all ages indicates that
      contraception is practiced mostly for birth spacing and that contraceptive
      methods have gained wide acceptance among younger cohorts. Good prospects are
      seen for further intensification of fertility declines in East Africa and urban
      West Africa. However, low levels of education and high child mortality make rapid
      changes unlikely in rural West Africa.

PMID- 9561667
TI  - The influence of traditional religion on fertility regulation among the Kassena
      Nankana of northern Ghana.
AB  - This article presents findings from a study of the influence of traditional
      religion on reproductive preferences of Kassena-Nankana lineage heads in northern
      Ghana. Seven reproductive preference questions were administered to nine lineage
      heads who are primary practitioners of the cult of soothsaying. With the
      assistance of soothsayers, interviews were repeated in conjunction with the
      invocation of religious rites in order to determine the views of ancestral
      spirits on the seven questions. Pairs of lineage head and ancestral interviews
      are compared to determine the role of traditional religion in shaping male
      reproductive preferences. Interview pairs reflect a shared preference for sons,
      large compounds, and a growing lineage. Findings nonetheless show that some
      ancestral spirits want small families, some even wanting fewer children than
      corresponding lineage heads. Spiritual consultations are nondogmatic and open to
      external ideas and influences, suggesting that family planning introduction will
      not encounter systematic religious opposition among the Kassena-Nankana.

PMID- 9561668
TI  - Postpartum contraceptive use in Bangladesh: understanding users' perspectives.
AB  - Qualitative and quantitative data are used to explore postpartum contraceptive
      use in two populations in Bangladesh. Findings from in-depth interviews with
      contraceptive users illustrate that women are primarily concerned with their own
      and their newborn child's health and well-being in the period following
      childbirth. In addition, women are aware of a diminished risk of pregnancy during
      the period of postpartum amenorrhea. These perceptions, plus a belief that modern
      methods of contraception are "strong" and potentially damaging to health, mean
      that the majority of women are reluctant to adopt family planning methods soon
      after birth, despite a desire to avoid closely spaced pregnancies.
      Supplementation of the child's diet is also shown to be an important factor
      determining the timing of postpartum contraceptive initiation. The findings
      suggest that current policies promoting contraception to women in the immediate
      postpartum period are inappropriate for many Bangladeshi women.

PMID- 9561669
TI  - Three strategies to promote sustainability of CEMOPLAF clinics in Ecuador.
      Centros Medicos de Orientacion y Planificacion Familiar.
AB  - The continuing trend of donor attention and resources away from Latin America
      threatens the sustainability of nongovernmental family planning organizations in
      that region. Managers can improve sustainability through cost control, cost
      recovery, and income generation. The Population Council's INOPAL II and INOPAL
      III projects and Family Health International assisted CEMOPLAF, an Ecuadoran
      private voluntary organization, in carrying out operations research in each of
      these areas. Studies included cost-savings analysis from altering IUD revisit
      norms (cost control), an ability-to-pay study that showed potential gains from
      increased prices for reproductive health services (cost recovery), and a
      feasibility study to estimate income from ultrasound services (income
      generation). Results indicate that any one intervention will probably have a
      limited impact, and that managers likely will need to undertake several
      initiatives simultaneously to make significant progress toward sustainability.

PMID- 9561670
TI  - The impact of type of employment on women's use of prenatal-care services and
      family planning in urban Cebu, the Philippines.
AB  - This study re-evaluates the relationship of urban women's employment to their
      health-service and contraceptive use, drawing on data from the Cebu Longitudinal
      Health and Nutrition Survey. Multivariate analyses reveal significant differences
      across types of work for the likelihood of both obtaining timely prenatal care
      and practicing contraception at one year postpartum. Wage workers in white-collar
      jobs are significantly more likely than those not employed for pay to have
      obtained prenatal care and are substantially more likely to have adopted a
      contraceptive method in the year following childbirth. Women who are self
      employed also are significantly more likely than those not employed for pay to be
      using contraceptives. Blue-collar wage work and piecework employment have no
      relationship to either dependent variable. These findings suggest that work
      related autonomy encourages women to exercise control in other areas of their
      lives.

PMID- 9561671
TI  - Laying the foundation for girls' healthy futures: can sports play a role?

PMID- 9561672
TI  - Update of current immunosuppressive drugs used in clinical organ transplantation.
AB  - The outcome of clinical organ transplantations has improved considerably during
      the last decade, mainly due to the introduction and administration of new drugs
      for immunosuppression. Our knowledge of basic immune reactions has led to the
      development of a variety of new immunosuppressants that promise higher
      selectivity and additive or synergistic drug effects combined with less toxicity.
      This article gives a brief update of the immunosuppressive currently used in
      clinical organ transplantation.

PMID- 9561673
TI  - Do noninherited maternal antigens (NIMA) enhance renal graft survival?
AB  - To test the hypothesis that noninherited maternal antigens (NIMA) can modulate
      the alloreactivity of infant cells and provide protection for renal transplant
      recipients, a study of renal transplantations performed between 1980 and 1991 was
      undertaken. The survival rate of grafts with a mismatched antigen identical to
      the NIMA was compared to that of grafts in which the mismatched antigen was not
      identical to the NIMA. In the case of HLA-A mismatches, graft survival rates were
      significantly better for NIMA-mismatched transplants: 94% and 83% at 1 and 3
      years, respectively, for single NIMA HLA-A mismatched transplants, and 83% and
      67% when both HLA-A antigens were mismatched, compared to 76% and 68% (one non
      NIMA HLA-A mismatch) and 67% and 45% (two non-NIMA HLA-A mismatches). Our results
      suggest that some class I NIMA-mismatched antigens are not harmful to renal
      transplant recipients.

PMID- 9561674
TI  - Expression of HSP 70 as a potential prognostic marker for acute rejection in
      human liver transplantation.
AB  - In experimental models, the synthesis of heat shock protein 70 (HSP 70) has been
      recognized as an intracellular response to ischemia and reperfusion, insults
      inherent to transplantation. In this study, the HSP response in early stages of
      human liver transplantation was investigated. HSP 70 mRNA expression was detected
      by means of reverse transcriptase (RT)-PCR in liver biopsies (n = 28) and in
      cells obtained from the organ perfusate (n = 14) following cold preservation. The
      expression of HSP 70 differed substantially between individuals. Retrospective
      analysis revealed a close correlation of the amount of HSP 70 mRNA in perfusate
      cells and biopsies with the onset of organ dysfunction due to early graft
      rejection. Patients with early graft rejection had a significantly lower amount
      of HSP 70 mRNA than patients without rejection. These results suggest a
      protective role of HSP 70 expression. Low levels of HSP 70 may, therefore,
      represent a prognostic marker for early graft rejection.

PMID- 9561675
TI  - An immunosuppressive regimen using FTY720 combined with cyclosporin in canine
      kidney transplantation.
AB  - FTY720 induces apoptosis, specifically in lymphocytes, and prolongs allograft
      survival in rats and dogs. The purpose of this study was to define an effective
      range of FTY720 doses that could be combined with a suboptimal dose (10 mg/kg) of
      cyclosporin for canine kidney allograft recipients. The combination significantly
      prolonged allograft survival in all groups receiving FTY720 at a dose of 0.1,
      0.3, 1.0, or 3.0 mg/kg. None of the recipients died due to notable side effects
      of the drug. In peripheral blood, the number of lymphocytes was extremely low,
      whereas the percentage of granulocytes increased during FTY720 administration. No
      significant difference in cyclosporin trough levels was observed between the
      cyclosporin-alone group and the combination groups. We conclude from the present
      study that FTY720 has a potent effect at an extremely low dose and a wide
      therapeutic window when combined with cyclosporin in canine kidney transplants.

PMID- 9561676
TI  - Phenotypic and functional characteristics of intestinal intraepithelial
      lymphocytes during acute rejection of small intestinal allografts.
AB  - Infiltration of a transplanted organ by host lymphoid cells is the hallmark of
      acute rejection. However, after intestinal transplantation, physiological
      lymphocyte migration may lead to host cell infiltration of the graft even in the
      absence of rejection. It is unclear whether this lymphocyte migration also
      involves the intraepithelial compartment of the graft or whether infiltration
      there is indicative of acute rejection. We demonstrate here that host cell
      infiltration of the intestinal mucosa occurs both during acute rejection of a
      small bowel allograft and, to a lesser extent, when rejection is prevented by
      immunosuppression with FK506. The infiltrating host cells consisted of CD3+ T
      cells with a predominant CD4-CD8+ phenotype resembling intraepithelial
      lymphocytes (IELs). Functional studies showed that the nonspecific cytolytic
      activity of IELs was not affected by acute rejection or by immunosuppression with
      FK506. These findings indicate that host cell infiltration of the intestinal
      mucosa does not connote an ongoing acute rejection. Furthermore, the decreased
      mucosal barrier function during acute rejection of intestinal allgrafts is
      probably not due to impaired cytolytic activity of IELs.

PMID- 9561677
TI  - Delayed primary closure of the abdominal wall after cadaveric and living related
      donor liver graft transplantation in children: a safe and useful technique.
AB  - Due to the shortage of size-matched liver donors, relatively oversized liver
      grafts (even after ex situ volume reduction) are frequently used for liver
      transplantation in children. This was recently observed when livers from large,
      living related donors were procured for transplantation in very small recipients.
      Given that abdominal hyperpressure can compromise vascular flow in the new graft,
      primary closure of the abdomen was delayed by temporary Silastic prosthetic
      closure in selected cases. The new technique was original in that the skin was
      closed, avoiding fluid loss and reducing the risk of infections reported with
      other techniques, and in that reoperation allowed for a delayed, but primary
      type, closure (fascia and skin) that resulted in an esthetically correct aspect.
      Over a period of 7 years, 330 pediatric liver transplantations were performed,
      and delayed prosthetic closure was achieved successfully and safely in 47 cases.
      The present report outlines this clinical experience.

PMID- 9561678
TI  - Infection rates with and without T-tube splintage of common bile duct anastomosis
      in liver transplantation.
AB  - Stenting the bile duct over a T-tube after orthotopic liver transplantation (OLT)
      is the preferred method of biliary reconstruction. However, because of
      complications associated with the use of the T-tube, we evaluated the effect of
      various biliary anastomoses following 100 consecutive OLT (83 records were
      available for long-term evaluation) and assessed the clinical outcome of
      abandoning routine T-tube splintage. Of 16 OLT recipients with T-tube splintage
      (one died immediately following OLT and was excluded from the study), 6 patients
      (40%) developed six episodes of septicaemia secondary to biliary and/or intra
      abdominal sepsis. Four of these six patients had a biliary leak (27%). Of 57
      patients with duct-to-duct anastomosis without T-tube splintage, 7 patients
      developed biliary leak (12.3%) and only 1 developed septicaemia (1.7%) secondary
      to biliary and intra-abdominal sepsis (P = 0.0002). Of 11 patients with either a
      gallbladder conduit or Roux loop, only 1 patient had a biliary leak (9%) and
      there were no septicaemic episodes. In conclusion, direct duct-to-duct
      anastomosis resulted in significantly less morbidity due to infection without T
      tube splintage than the use of a T-tube following OLT, but there were no
      significant differences in leakage and stricture rates.

PMID- 9561679
TI  - Nonfreezing cryopreservation--a possible means of improving long-term transplant
      function?
AB  - Improving organ preservation techniques for transplantation is one of the most
      important goals of transplantation research. We have established a new,
      nonfreezing cryopreservation method to optimize the viability of rat kidneys for
      transplantation with up to 4 M dimethylsulphoxide (DMSO) in EuroCollins solution
      (EC) at -5 degrees C to -15 degrees C. We have confirmed the occurrence of a
      tubular and glomerular defect pattern that mediates acute tubular necrosis (ATN)
      and that may be a cause of major histocompatibility complex (MHC) independent
      immunological components of chronic transplant rejection. The extent of this
      defect [transplant survival and function, 31P-NMR spectroscopy, histological
      defect index] in the nonfreezing cryopreserved groups (n = 22) is significantly
      (P = 0.017) lower than in the simple cold storage group (n = 12). Quality and
      localization of the lesions in kidney transplants can elucidate the context of
      organ preservation, progressive hyperfiltration defects, and the occurrence of
      graft failure without elevated frequency of acute rejection episodes. These
      results indicate that further efforts to provide higher pretransplant organ
      viability without using it to prolong cold storage intervals may provide better
      insight into MHC-independent factors of chronic transplant failure and may result
      in improved long-term transplant outcome.

PMID- 9561680
TI  - Lipid abnormalities in stable liver transplant recipients--effects of
      cyclosporin, tacrolimus, and steroids.
AB  - Dyslipidemia is common after liver transplantation, but the underlying mechanisms
      are largely unknown. We studied the lipid profile of 27 liver transplant
      recipients randomized to received either cyclosporin (CyA, n = 14) or tacrolimus
      (n = 13) and compared them with 20 healthy, matched controls. Before
      transplantation, patients presented low total and low-density lipoprotein (LDL)
      cholesterol (as compared to controls) that increased shortly, i.e., 3 months,
      after transplantation. Eighteen months post-transplantation, total and LDL
      cholesterol levels decreased to pre-transplant values but tended to remain higher
      in CyA-treated patients. However, at that time, prednisone treatment was more
      prevalent among CyA-treated than tacrolimus-treated patients and fully accounted
      for the difference in cholesterol levels. Indeed, regardless of therapy, patients
      not receiving prednisone exhibited lower cholesterol levels than prednisone
      treated patients and controls. We conclude that prednisone therapy, rather than
      CyA or tacrolimus immunosuppression, seems to be the major determinant of
      increased cholesterol levels.

PMID- 9561681
TI  - Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early
      graft function in liver transplantation.
AB  - Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks
      coagulating activity. The aim of this study was to determine if the presence of
      DCP in the donor could be used as a marker of post-transplant graft function. We
      collected data and serum samples on 90 organ donors. DCP level was correlated
      with donor-specific factors and with graft function intraoperatively and in the
      early post-transplant period. Twenty-seven donors (30.0%) had positive DCP levels
      before harvesting. Although recipients were similar in demographics, preoperative
      liver function, and primary disease distribution, patients transplanted with
      livers from DCP-positive donors needed significantly more intraoperative
      transfusion. Furthermore, donor DCP positivity was identified as a preoperative
      risk factor for poor early graft function based on multivariate analysis (odds
      ratio = 6.58, P = 0.0032). Our findings suggest that DCP is another valuable
      marker for evaluating the quality of donor livers.

PMID- 9561682
TI  - Arterialization of the portal vein in pediatric liver transplantation. A report
      of two cases.
AB  - Portal vein arterialization (PVA) is an acquired concept in shunt surgery for
      portal hypertension. This technique, recently described as both a temporary and
      permanent procedure in adult liver transplantation, is reported by the authors in
      two cases of pediatric transplantation. The indication was low portal blood flow
      after reperfusion with poor graft function due to persistence of spontaneous
      retroperitoneal venous shunts. In both cases described, PVA allowed for
      satisfactory macroscopic liver reperfusion. The increase in portal blood flow
      from 150 to 500 ml/min in the second patient enabled the liver to be reperfused
      correctly and led to successful transplantation. The graft function in both cases
      improved in the 1st postoperative week, but the 1st patient 2 months after
      transplantation. Signs of hepatic hyperarterialization occurred in the second
      patient and this necessitated a dearterialization of the portal vein 2 weeks
      later. Although the benefit of this procedure appears to be beyond doubt in the
      immediate post-operative period, we have no data on long-term arterialization. We
      do think that PVA can be performed in pediatric liver transplantation, but it may
      need to be done only in special, individual situations when no valid alternative
      can be proposed, such as in the absence of a mesenteric vein and/or the presence
      of spontaneous retroperitoneal venous shunts.

PMID- 9561684
TI  - Evaluation of long-term follow-up of glomerular function in renal transplant
      recipients.

PMID- 9561683
TI  - Detection of occult disease in tissue donors by routine autopsy.
AB  - The transmission of infectious and neoplastic diseases is a potential risk of
      tissue allografting. In this study, we analyzed the occurrence of occult disease
      in tissue donors as detected by standard screening and autopsy. Whereas 18% of
      the potential donors initially evaluated were eliminated on the basis of their
      medical and social histories, laboratory screening and autopsy revealed that an
      additional 9% of tissue donors had undetected, transmissible disease that
      prohibited tissue donation. This report emphasizes once again the risk of occult
      disease being transplanted with grafts and the need for autopsy to reduce the
      likelihood of this occurring. If donor selection, appropriate screening tests,
      and autopsy are carefully carried out, the risk of transmitting diseases from
      tissue allografts can be kept to a minimum.

PMID- 9561685
TI  - Physiology of body fluids in the horse.
AB  - This article presents a brief overview of the physiology of homeostasis in the
      horse and discusses the units of measurement by which dissolved electrolytes are
      assessed. Differences in electrolyte composition between compartments of the body
      and the manner in which water is exchanged between them are reviewed. The
      mechanisms by which alterations in osmolality and effective circulating volume
      are detected and the physiological responses to those alterations are presented.

PMID- 9561687
TI  - Thermoregulation. Base mechanisms and hyperthermia.
AB  - Metabolic HP is extremely high during exercise in horses. Thermoregulation in
      horses is primarily dependent on evaporative heat loss from sweating in
      particular. Under thermoneutral conditions, these mechanisms are sufficient to
      allow horses to perform high-intensity exercise for long periods. Under thermally
      stressful conditions, particularly in high ambient humidity, the efficiency of
      evaporative heat loss mechanisms is compromised and may result in horses
      developing hyperthermia. Early recognition and vigorous treatment are essential
      to limit the consequences of heat stress in horses. Meticulous planning and
      management of equestrian events that are held under thermally stressful
      conditions are essential to ensure the welfare of competing horses and their
      riders. The conditioning program of horses expected to compete under thermally
      stressful conditions must also make adequate provision for acclimatization to the
      hot, humid conditions.

PMID- 9561686
TI  - Effect of exercise on fluid balance and renal function in horses.
AB  - Exercise places large demands on the equine cardiovascular system which are
      further complicated by environmental factors. In many respects, performance is
      limited by fluid and electrolyte stores and the ability to maintain
      cardiovascular and thermoregulatory stability in the face of severe sweat losses.
      Studies in the exercising horse have been primarily descriptive or associative,
      with only a limited number seeking to identify physiologic mechanisms associated
      with the control of fluid and electrolyte balance. More mechanistic studies are
      needed to fully understand the integration of the cardiovascular, endocrine, and
      renal systems in the defense of plasma osmolality, blood volume, and blood
      pressure.

PMID- 9561688
TI  - Effect of exercise on acid-base status of horses.
AB  - Exercise in horses is associated with a wide variety of physiological changes in
      fluid, electrolyte and acid base balance. The integration of physiologic and
      physiochemical mechanisms acts to minimize alterations in pH and enhance removal
      of carbon dioxide produced by exercising muscles. This article provides a
      description of the changes that take place during exercise and how these changes
      affect acid-base balance in the horse.

PMID- 9561689
TI  - Sweating. Fluid and ion losses and replacement.
AB  - In the horse, sweat is produced by apocrine glands which are present over most
      haired and nonhaired skin. Although sweat secretion is initiated under a number
      of circumstances, the central drive for sweating in response to a thermal
      stimulus is the primary mechanism for its production. Sweating is an essential
      and primary mechanism for heat dissipation during exercise or exposure to hot
      ambient conditions. The rate of sweat production will reflect the interaction of
      numerous factors, including exercise intensity, ambient conditions, state of
      hydration, and the training or heat acclimation status of the individual horse.
      Thus, the sweating rates produced in response to an exercise-induced thermal load
      can be further increased by high ambient temperature or humidity which reduces
      evaporative efficiency, thereby contributing to the rate of rise in core body
      temperature. Equine sweat is an isotonic to slightly hypertonic secretion with
      sodium, chloride, and potassium contributing the major ionic components. The
      ionic composition of equine sweat is largely rate dependent and therefore is
      affected by factors such as ambient conditions and exercise intensity which
      result in elevations in sodium concentration in response to increases in sweating
      rate. Large sweat fluid losses associated with prolonged exercise will incur
      significant ion deficits, leading to alterations in skeletal muscle ion content
      and the potential for muscular dysfunction. With respect to exercise performance,
      however, the more important consequence of sweat fluid losses is the impairment
      of temperature regulation that accompanies severe dehydration. Although it is
      advantageous to restore a proportion of the fluid and ion losses incurred during
      prolonged exercise, few strategies will fully and safely replace the electrolyte
      losses incurred. Nevertheless, daily electrolyte supplementation of a good
      quality diet will provide an effective method of replacing sweat ion losses
      during training and competition under most ambient conditions.

PMID- 9561690
TI  - Thermoregulatory adaptations associated with training and heat acclimation.
AB  - The large metabolic heat load generated as a consequence of muscular work
      requires activation of thermoregulatory mechanisms in order to prevent an
      excessive and potentially dangerous rise in body temperature during exercise.
      Although the horse has highly efficient heat dissipatory mechanisms, there are a
      number of circumstances in which the thermoregulatory system may be overwhelmed,
      resulting in the development of critical hyperthermia. The risk for development
      of life-threatening hyperthermia is greatest when (1) the horse is inadequately
      conditioned for the required level of physical performance; (2) exercise is
      undertaken in hot and particularly, in hot and humid ambient conditions; and (3)
      there is an impairment to thermoregulatory mechanisms (e.g., severe dehydration,
      anhidrosis). Both exercise training under cool to moderate ambient conditions and
      a period of repeated exposure to, and exercise in, hot ambient conditions (heat
      acclimation) will result in a number of physiologic adaptations conferring
      improved thermoregulatory ability. These adaptations include an expanded plasma
      volume, greater stability of cardiovascular function during exercise, and an
      improved efficiency of evaporative heat loss as a result of alterations in the
      sweating response. Collectively, these adjustments serve to attenuate the rise in
      core body temperature in response to a given intensity of exercise. The magnitude
      of the physiologic adaptations occurring during exercise training and heat
      acclimation is a reflection of the thermal load imposed on the horse. Therefore,
      when compared with a period of training in cool conditions, the larger thermal
      stimulus associated with repeated exercise in hot ambient conditions will invoke
      proportionally greater thermoregulatory adaptations. Although it is not possible
      to eliminate the effects of adverse environmental conditions on exercise
      performance, it is clear that a thorough exercise training program together with
      a subsequent period of acclimatization will serve to ameliorate the impact of the
      environment. Based on our current understanding of the nature and extent of
      thermoregulatory adaptations in the horse, the following conclusions can be made:
      1. A 2- to 3-month period of exercise training geared toward the specific
      athletic endeavor to be undertaken will result in substantial improvements in
      thermoregulatory capacity and is an absolute requirement for horses required to
      compete in hot ambient conditions. 2. Although physical training in a cool
      environment improves physiologic responses to exercise at high ambient
      temperatures, a 2-week period of moderate exercise training in these more adverse
      conditions is necessary for optimization of thermoregulatory function and
      physical performance. 3. Heat acclimation does not reduce the need for close
      monitoring of horses during training and competition in the heat. This is
      particularly true in hot, humid ambient conditions, where the biophysical
      limitations to sweat evaporation can result in development of severe
      hyperthermia, regardless of the state of training or heat acclimation.

PMID- 9561691
TI  - Fluid, electrolyte, and acid-base responses to exercise in racehorses.
AB  - During both high-intensity and short-distance exercise, the high rate of expended
      energy is met by anaerobic oxidation of glucose to lactic acid; this is the main
      cause of metabolic acidosis observed during racing. In addition, plasma volume
      decreases because water moves from the vasculature to the intracellular and
      interstitial spaces at the onset of intense exercise. These fluid shifts,
      together with active ion-exchange between blood and tissue, cause marked changes
      in electrolyte concentrations. This article reviews the mechanisms of acid-base
      disturbances, fluid shifts, and electrolyte changes, and discusses related areas
      such as buffer capacity, lactic acid distribution, and the effects of training.
      The influences of health, dietary cation-anion balance, supplements, and
      medication such as creatine, sodium bicarbonate, and furosemide are emphasized.

PMID- 9561692
TI  - Fluid, electrolyte, and acid-base balances in three-day, combined-training
      horses.
AB  - Horses competing in 3-day, combined-training events develop a metabolic acidosis
      that is partially compensated for by a respiratory alkalosis immediately after
      phases B and D. By the end of phase C and 30 minutes to 2 hours after phase D,
      the acidosis is resolved by the oxidation of lactate, and a metabolic alkalosis
      prevails. A reduction in TBW and cation content occurs, which often is not
      replenished 12 to 24 hours after the event, even though the serum or plasma
      concentration of various constituents may be within normal limits. Hypochloremia
      and hypocalcemia, however, may persist 12 or more hours after the speed and
      endurance test. All of the data cited in this article are from horses that
      successfully completed their respective tests. Nevertheless, some horses
      developed substantial fluid and cation losses. In horses that are not well
      conditioned or in competitions in which terrain, footing, or hot environments
      increase the thermal load or decrease heat loss, greater losses of fluids and
      electrolytes can be expected. Body weight losses exceeding 5% and cation losses
      exceeding 4000 mEq/L occur in endurance horses suffering from exhaustion and
      synchronous diaphragmatic flutter. In one study, two thirds of the Na+ lost
      during exercise-induced sweating in cool, dry conditions was replenished from
      salt supplements added to a balanced forage and concentrated diet. Consequently,
      horses in regular training and competition may benefit from salt supplementation.
      The composition of the salt supplement and the amount fed should be based on the
      composition of the horse's diet, degree of work, and environmental conditions.
      Horses competing in a 3-day, combined-training event may be expected to have
      persistent losses of weight and cations, particularly if conditions result in
      heavy sweating. Many horses in the field studies had minimal changes in weight
      and cation balance compared with pre-event values. The diet and electrolyte
      supplementation of the horses in the majority of these studies were unknown;
      consequently, no firm conclusions may be made regarding the degree of weight,
      water, and cationic losses. It is likely that the horse's large intestine serves
      as a reservoir for both fluid and electrolytes so that performance is not
      diminished, despite losses demonstrated consistently in treadmill studies. Horses
      that are inadequately trained or have other systemic or musculoskeletal problems
      or those that are competing in hot conditions may develop a variety of metabolic
      problems. It is hoped that knowledge of the fluid and electrolyte losses may help
      in treating horses with metabolic problems and, more importantly, in improving
      management of horses in training and competition to prevent any loss of
      performance.

PMID- 9561693
TI  - Fluid and electrolyte balance in endurance horses.
AB  - In horses, fluid losses of 10L to 15L per hour can occur during endurance
      exercise under hot environmental conditions. The horse's sweat is hypertonic with
      respect to plasma, and large amounts of sodium, chloride and potassium are lost
      during prolonged exercise. Horses that reach exhaustive syndrome often show
      pronounced increases in plasma protein concentration. This could be an indication
      of failure of the compensatory fluid shift from the intracellular compartment
      caused by severe dehydration. Thorough physical examination by the ride
      veterinarian allows early recognition of dehydration and electrolyte imbalances.

PMID- 9561694
TI  - Treatment of exercise-induced dehydration.
AB  - One of the most common consequences of prolonged exercise is fluid and
      electrolyte depletion. Fluid and electrolyte losses during exercise may limit the
      horse's performance and, in extreme cases, jeopardize its health. To avoid or
      treat the deleterious effects of dehydration, fluid and electrolyte
      supplementation is essential. This article provides recommendations for fluid and
      electrolyte supplementation for horses involved in endurance-related events.

PMID- 9561695
TI  - Treatments affecting fluid and electrolyte status during exercise.
AB  - A number of feeding and management practices, dietary electrolyte supplements,
      and medications may affect fluid and electrolyte status in resting and exercising
      horses. The contents of the gastrointestinal tract of the equine athlete, unlike
      its human counterpart, are responsible for more than 10% of body weight. Although
      ingesta traditionally has been considered dead weight for the sprinting horse, it
      is a valuable reservoir of fluid and electrolytes that may be used during
      endurance exercise. Numerous strategies for hyperhydration of the equine athlete
      and for replacement of fluid and electrolytes lost via sweating were developed in
      preparation for competing in the hot and humid climate of the 1996 Olympic Games
      in Atlanta. These strategies have implications for all equine athletes.
      Medications, including sodium bicarbonate, furosemide, and acetazolamide commonly
      are used to enhance performance by either buffering alterations in fluid and
      electrolyte homeostasis or by ameliorating the effects of other conditions that
      may limit performance.

PMID- 9561696
TI  - The exhausted horse syndrome.
AB  - Exhaustion occurs in most equestrian sports, but it is more frequent in events
      that require sustained endurance work such as endurance racing, three-day
      eventing, trial riding, and hunting. Exhaustion is also more likely when an
      unfit, unacclimatized, or unsound horse is exercised. Mechanisms that contribute
      to exhaustion include heat retention, fluid and electrolyte loss, acid-base
      imbalance, and intramuscular glycogen depletion. Clinical signs include elevated
      temperature, pulse, and respiratory rate; depression; anorexia; unwillingness to
      continue to exercise; dehydration; weakness; stiffness; hypovolemic shock;
      exertional myopathy; synchronous diaphragmatic flutter; atrial fibrillation;
      diarrhea; colic; and laminitis. Treatment includes stopping exercise; rapid
      cooling; rapid large volume intravenous or oral fluid administration; and
      nonsteroidal anti-inflammatory drug administration.

PMID- 9561697
TI  - Residual activity of anticoccidial drugs in chickens after withdrawal of
      medicated feeds.
AB  - Seven anticoccidial drugs commonly used in poultry (diclazuri), monensin,
      salinomycin, halofuginone, nicarbazin, robenidine, amprolium, and lasalocid) were
      tested for residual activity after withdrawal. In each test, the products were
      given at the recommended level to cages of 10 broiler chickens. Oral inoculation
      with coccidia was given after withdrawal of medication. Birds pretreated with 1
      ppm of diclazuril and inoculated with Eimeria tenella after drug withdrawal had
      normal weight gain and very low lesion scores. Residual activity depleted
      gradually over several days, as shown by higher lesion scores when medication was
      withdrawn for up to 3 days before inoculation. Similar results were observed when
      young birds were inoculated with a mixture of E. tenella, E. maxima and E.
      acervulina, and also when birds were given diclazuril to market weight (6 weeks
      of age) and inoculated with a mixture of six species of Eimeria (The above
      species plus E. brunetti, E. mitis, and E. necatrix) after withdrawal of
      medication for 2 days. In contrast, there was no evidence of residual
      anticoccidial activity with nicarbazin, halofuginone, lasalocid, amprolium,
      salinomycin or monensin. Overall, the residual activity was unique to diclazuril.

PMID- 9561698
TI  - Comparison between enzyme-linked immunosorbent assay, indirect fluorescent
      antibody and rapid conglutination tests in detecting antibodies against Babesia
      bovis.
AB  - The performance of an enzyme-linked immunosorbent assay (ELISA), an indirect
      fluorescent antibody test (IFAT) and a rapid conglutination test (RCT) for the
      detection of antibodies against Babesia bovis, was evaluated with 462 cattle sera
      from Bahia State; Brazil. The results showed a concordance of 96.6% between the
      ELISA and IFAT, 90.5% between the ELISA and RCT, and 91.8% between the IFAT and
      RCT. Although the prevalence rates determined by ELISA (97.2%) and IFAT (96.8%)
      were higher than that indicated by the RCT (92.9%), performances of the three
      serological tests were very similar and characterized the region studied as
      enzootically stable to B. bovis.

PMID- 9561699
TI  - Characterization of Anaplasma isolates from eland (Taurotragus oryx).
      Pathogenicity in cattle and sheep and DNA profiles analysis.
AB  - Two eland Anaplasma isolates, AnapE1, from Kenya, and AnapE2, from South Africa
      were characterised. Their characterization was based on their pathogenicity to
      intact and splenectomized cattle and sheep and also their DNA profiles. Their DNA
      profiles were analysed and compared to Anaplasma marginale, A. ovis and A.
      centrale after endonuclease restrictions and probing with Anaplasma DNA probes,
      AC5-12 and AC-1. The results of the pathogenicity trials showed AnapE1 to be
      similar to A. ovis and AnapE2 an isolate of A. marginale. On DNA profiles, AnapE1
      was close to A. ovis, with differences that occur even in same Anaplasma species
      isolates from different locations. On the other hand, AnapE2, resembled one of
      the A. marginale isolates known to occur in South Africa. The DNA profiles
      correlated well with the pathogenicity results. It is concluded that elands are
      carriers of both A. marginale and A. ovis parasites and are therefore important
      reservoirs that need attention in epidemiology of anaplasmosis.

PMID- 9561700
TI  - Therapeutic efficacy of hyperimmune bovine colostrum treatment against clinical
      and subclinical Cryptosporidium serpentis infections in captive snakes.
AB  - Therapy based on the protective passive immunity of Hyperimmune Bovine Colostrum
      (HBC) (raised against Cryptosporidium parvum in dairy cows immunized during
      gestation) was tested for heterologous efficacy in subclinical and clinical
      infections of 12 captive snakes with C. serpentis. Six gastric HBC treatments of
      1% snake weight at 1-week intervals each, have histologically cleared C.
      serpentis in three subclinically infected snakes, and regressed gastric
      histopathological changes in one of these snakes. In all snakes, each subsequent
      HBC treatment significantly decreased the number of oocysts recovered in gastric
      lavage eluants (P < 0.03). The treatments induced oocyst-negative gastric eluants
      and stools in all snakes, and improved clinical signs of infection. Clinically
      infected snakes displayed severe histopathological changes in the gastric region;
      however, the numbers of developmental stages of C. serpentis were moderate.
      Considering the severity of pathology, much lower than expected pathogen numbers
      were observed, and it is believed that clinically infected snakes did not have
      enough time to repair tissue damage that had occurred over the years of
      infection. As the HBC treatment was safe and highly efficacious, it is
      recommended to gastrically administer the HBC therapeutically to snakes that are
      clinically or subclinically infected with C. serpentis. Hyperimmune bovine
      colostrum can also be used in snake supportive therapy or prophylaxis.

PMID- 9561701
TI  - A survey of tick-borne bacteria and protozoa in naturally exposed dogs from
      Israel.
AB  - Antibody reactivity against seven bacterial or protozoal pathogens was measured
      in sera derived from 40 dogs suspected of a tick-borne disease. Sera from 73%
      (29/40) of the dogs reacted with three or more test antigens. Seroreactivity was
      most prevalent to Babesia canis antigen (90%) followed by Babesia gibsoni (75%),
      Ehrlichia canis (63%), Rickettsia conorii--Moroccan strain (58%), Rickettsia
      conorii--Israeli strain no. 2 (28%), Borrelia burgdorferi (10%) or Bartonella
      vinsonii (berkhoffii) (10%). Seroconversion documented in seven dogs, supported
      an acute phase diagnosis of ehrlichiosis in four dogs, R. conorii infection in
      three dogs and babesiosis in one dog. In the remaining dogs, correlation of
      clinical abnormalities with increased seroreactivity was not established through
      the design of this study. Although Lyme borreliosis has not been reported in
      people in Israel, Western blot analysis for antibodies reactive to B. burgdorferi
      identified genus-specific antiflagellin antibodies indicating that dogs in Israel
      are exposed to a Borrelia species. Identification of species-specific
      seroreactivity was not possible and infection with a Borrelia species other than
      B. burgdorferi is likely. Seroreactivity to B. vinsonii (berkhoffii) in dogs
      outside the USA is reported here for the first time.

PMID- 9561702
TI  - Prevention of Eimeria alabamensis coccidiosis by a long-acting
      baquiloprim/sulphadimidine bolus.
AB  - Twelve calves aged 6-10 months, and 12 calves aged 10-16 months were turned out
      onto a permanent pasture known to have been contaminated with oocysts of Eimeria
      alabamensis during the previous year. Two days after turnout, six of the older
      calves and six of the younger were each treated with one bolus per 200 kg
      bodyweight containing 1.6 g baquiloprim and 14.4 g sulphadimidine. The other 12
      calves were left untreated. The excretion of Eimeria oocysts, the faecal dry
      matter and the weight gain of treated and untreated calves within each age group
      were compared during the first 3 weeks on pasture to assess the efficacy of the
      bolus in preventing E. alabamensis coccidiosis. All the older of the untreated
      calves and four of the younger developed gruel-like to watery diarrhoea 4-7 days
      after turnout. The faecal consistency of the treated calves remained firm and
      they lost significantly less weight than the control calves during the first 13
      days on pasture. The treated calves also excreted significantly fewer oocysts
      during the first 20 days of grazing; their oocyst excretion remained low during
      days 8-10 when all but one of the diarrhoeic control calves excreted more than
      850,000 oocysts per gram faeces (OPG). Starting on days 12 to 14 the oocyst
      excretion of 8 of the treated calves increased to 20,000-65,000 OPG and of 2
      calves to 210,000-240,000 OPG. There was no difference in oocyst output between
      treated and untreated calves from the fourth week of grazing and no difference in
      weight gain among the younger calves. In the older calves there was a tendency
      for the untreated calves to gain more weight than treated calves.

PMID- 9561703
TI  - Some epizootiological and clinical aspects of ovine babesiosis caused by Babesia
      ovis--a review.
AB  - The study shows a close relationship between incidence of ovine babesiosis caused
      by Babesia ovis and the activity period and distribution area of the vector tick
      Rhipicephalus bursa. The most important factor limiting the distribution of this
      tick is a decrease in humidity. In general, it is absent from areas with an
      average annual rainfall of less than about 300 mm. The rate of parasitaemia and
      the degree of anaemia were not correlated. Decrease of the packed-cell volume
      ranged from 30 to 40%. Parasitized erythrocytes were not observed to block
      capillaries in the brain, which explained the absence of nervous symptoms in
      acute babesiosis. The kidney was the most severely affected organ, exhibiting
      acute glomerulonephritis. The lesions observed were suggestive of vascular
      alteration and vascular stasis, leading to anoxia of the tissues. A disseminated
      intravascular coagulation (DIC) syndrome was recorded in sheep infected with
      babesiosis. Biochemical studies revealed possible damage to the liver and
      kidneys. Most of the lambs (85%) that were infested with larvae, and all lambs
      infested with adult R. bursa ticks reacted serologically to B. ovis antigen. The
      serological reactions following infestation with the larvae occurred much later
      than those following infestation with the adult stage. Both transovarial and
      transstadial transmission of the parasite were demonstrated. A study of
      antibodies to B. ovis using IFAT in hoggets and ewes revealed high serological
      prevalence, i.e., 88.9% in ewes and 84.5% in hoggets. No marked seasonal
      fluctuation was observed. The serological findings, in addition to the fact that
      one splenectomised lamb reacted to larval infestation with acute ovine
      babesiosis, show that the preimaginal stages of R. bursa occurring in the winter
      can transmit B. ovis, usually causing a sub-clinical disease. This might play a
      major role in pre-immunizing and strengthening the premunition of the sheep
      against the main spring challenge by the adult ticks. The sub-clinical reactions
      are probably due to the low infection rate of the preimaginal stages of R. bursa
      by B. ovis parasites.

PMID- 9561704
TI  - Coccidial infections of goats in Selangor, peninsular Malaysia.
AB  - Coccidial infections were studied in goats in the state of Selangor (peninsular
      Malaysia) during a 12-month period. The study included 10 smallholder farms on
      which kids were monitored for faecal oocyst counts from birth until 1-year old.
      Eimeria oocysts were found in 725 (89%) of 815 faecal samples examined. Nine
      species of Eimeria were identified. The most prevalent were E. arloingi, found in
      71% of the samples, E. ninakohlyakimovae (67%), E. christenseni (63%) and E.
      alijevi (61%). The other species found were, E. hirci, E. jolchijevi, E.
      caprovina, E. caprina and E. pallida, present in 34, 22, 12, 9 and 4% of the
      samples, respectively. Oocyst counts were significantly higher in animals of less
      than 4-months old (P < 0.05). High oocyst counts were mainly caused by non
      pathogenic species. Poor hygienic conditions were found to be associated with a
      higher intensity of coccidial infections. Mortality rates in kids could not be
      related to the intensity of coccidial infections.

PMID- 9561705
TI  - Effects of acute bovine trypanosomosis (Trypanosoma vivax) on plasma kinetics of
      intravenously administered lactose.
AB  - Four calves infected with Trypanosoma vivax and four uninfected control calves
      were each injected intravenously with repeated doses of 0.5 g lactose kg-1 body
      weight, thrice daily at intervals of 4 h. Plasma samples were collected at
      specified time intervals and analysed for lactose. Pharmacokinetic parameters
      were calculated from the data. T. vivax infection delayed excretion of lactose
      from the body, thus leading to significantly (P < 0.001) increased biological
      half life (t1/2) and a significantly (P < 0.001) reduced elimination rate
      constant for lactose in the body. The apparent volume of distribution and total
      clearance of lactose were not affected by the infection. T. vivax infection also
      appeared to cause accumulation of lactose in the plasma after repeated
      intravenous administration.

PMID- 9561706
TI  - Depressed immunity to a Salmonella typhimurium vaccine in mice experimentally
      parasitized by Taenia crassiceps.
AB  - To assess the immunological status of mice parasitized with Taenia crassiceps
      metacestodes, 6-month old female BALB/c mice experimentally parasitized with T.
      crassiceps and immunized with Salmonella typhimurium antigens were infected with
      S. typhimurium virulent bacilli (1.6 x LD50). Both T. crassiceps-parasitized and
      immunized and parasitized mice showed a very high susceptibility to infection
      (**P < 0.01) with higher bacteremia than control and immunized-control animals
      and produced a reduced IgG response to S. typhimurium, antigens (* P < 0.05).
      This indicates that T. crassiceps is able to preclude development of immunity to
      S. typhimurium, because appropriate antibody production to a heterologous
      antigenic stimulus did not take place, and the bacteremia results suggest the
      parasitosis altered the mononuclear phagocyte system. It has been demonstrated
      that Taenia solium metacestodes produce a small RNA molecule in culture which
      suppresses humoral and cellular responses against homologous antigens in mice. We
      propose that T. crassiceps may be actively synthesizing such a factor, apart from
      other simultaneously acting immunomodulatory mechanisms, to induce an
      immunosuppressed state favorable to its development in the host.

PMID- 9561707
TI  - Purification of larval Taenia solium antigens by isoelectric focusing.
AB  - By preparative isoelectric focusing in a rotating ampholine column, crude cystic
      membrane (M) or fluid (F) antigens of larval Taenia solium were each separated
      into 20 fractions. M fractions were less specific and sensitive than F fractions
      in detecting cysticercosis antibodies in pig serum. Among the F fractions, F15
      showed the best potential to serve as a screening antigen. It contained 18
      polypeptides, with pI 5.3-8.2 and a specific epitope of 25 kDa which was detected
      by immunoblotting. Although F15 showed slight cross-reactions with heterologous
      antisera in double-antibody IgG enzyme-linked immunosorbent assays (ELISA), it
      yielded the highest absorbance values when tested against homologous antisera.
      The antigen was used to screen sera samples from 4870 pigs slaughtered in Hong
      Kong and five other Chinese cities for cysticercosis antibodies by double
      antibody ELISA, Falcon Assay Screening Test (FAST)-ELISA and enhanced
      chemiluminescent immunoassay. The results varied significantly between assays.
      However, the samples collected from Shenzhen yielded the highest positive rates.
      Enhanced chemiluminescent immunoassay based on camera-luminometry was found
      suitable for use under field conditions.

PMID- 9561708
TI  - Seasonal infection pattern of gastrointestinal nematodes of beef cattle in Minas
      Gerais State--Brazil.
AB  - Tracer calves were used to assess the seasonality of infections of
      gastrointestinal parasites in beef cattle extensively raised at a farm in the
      State of Minas Gerais, Brazil. Tracer calves acquired infections during all
      months of the year, however, highest worm burdens were observed in the rainy
      season. The following nematode species were recovered from tracer calves:
      Cooperia punctata, C. spatulata, C. pectinata, Haemonchus similis, H. placei,
      Oesophagostomum radiatum, Trichostrongylus colubriformis, T. axei, Bunostomum
      phlebotomum and Trichuris discolor. Cooperia was most prevalent, representing
      74.4% of the total of all nematodes recovered. This was followed by Haemonchus
      19.2%, Oesophagostomum 4.5%, Trichostrongylus, Trichuris and Bunostomum,
      represented less than 1% of the total. Thirty Nellore cows with calves were used
      to evaluate the dynamics of the infections. The cows were the principal source of
      contamination to pasture and to infection of suckling calves during the pre
      weaning period, and probably, also contributed to increased infection of weaned
      calves at the beginning of the rainy season. Strongyloides was the first
      infection observed in the calves. The peak egg count was observed in the 2nd
      month, however, all Strongyloides egg counts became negative in the 7th month.
      Strongylate nematode egg counts were low in calves from the 3rd month of age
      onward, and increased gradually until calves were 1 year old. A gradual reduction
      then occurred until the end of the trial. From the 3rd month onward Cooperia and
      Haemonchus infective larvae (L3) were most prevalent in fecal cultures. Fecal
      cultures after the 4th month also resulted in recoveries of Oesophagostomum,
      Trichostrongylus, and Bunostomum L3. Cooperia was the predominant genus in fecal
      cultures until the calves were 9 months old. After the calves were 9 and 12
      months of age, L3 of Cooperia and Oesophagostomum, respectively decreased in
      prevalence. Trichostrongylus and Bunostomum L3 were only minimally present in the
      fecal cultures at this time.

PMID- 9561709
TI  - Experimental cyathostome challenge of ponies maintained with or without benefit
      of daily pyrantel tartrate feed additive: comparison of parasite burdens,
      immunity and colonic pathology.
AB  - Eighteen mixed-breed, naturally infected ponies ranging in age from 1 to 16 yr
      and four cyathostome-naive ponies reared and maintained under parasite-free
      conditions ranging in age from 1 to 4 yr were used in this study. Naturally
      infected ponies were treated with 1 dose of ivermectin (IVM) at 200 micrograms kg
      1, followed by a 5-day regimen of oxibendazole (OBZ) at 20 mg kg-1 to remove
      existing cyathostome burdens; cyathostome-naive control ponies were treated with
      IVM alone. The naturally infected ponies were matched on age and gender, then
      randomly assigned to one of three treatment groups of six animals per group; the
      four cyathostome-naive ponies constituted a fourth group. Following OBZ
      treatment, Group 1 ponies were treated with pyrantel tartrate (PT) in their
      pelleted ration; the remaining ponies received only the pelleted ration.
      Beginning on experiment Day 3, a daily challenge infection of 10(4) mixed
      cyathostome larvae was administered orally to ponies of Group 1, Group 2 and the
      cyathostome-naive controls. Group 3 ponies served as unchallenged controls to
      determine residual parasite burdens following IVM/OBZ treatment. Necropsy
      examinations were performed on three Group 3 ponies on Day 1; the remainder of
      the necropsy examinations began on Day 41. Cyathostome burdens were evaluated by
      recovery of larvae and adults from the luminal contents, by digestions of the
      intestinal mucosa, and by mural transillumination of full-thickness intestinal
      sections. Differences in postchallenge clinical responses were also compared.
      Necropsy examinations included comparisons of grossly visible inflammation of the
      large bowel, weights of biopsy specimens from each region, and histologic
      evaluations of these biopsies. Parasite recoveries at necropsy indicated a strong
      protective effect derived from daily PT treatment. Mean weights of intestinal
      biopsies corresponded with worm burdens, but histological evaluation did not
      reveal architectural or cellular changes to account for the increase in weight;
      therefore, edema was suspected. A strong age-related resistance to challenge
      infection was apparent in both the PT-treated and control groups by virtue of the
      lower mean worm burdens found in older ponies compared to younger ponies of the
      same treatment group; however, daily PT treatment of older ponies reduced the
      variability of their worm burdens to a uniformly low level. Comparisons of
      luminal and mucosal parasite burdens of age stratified nontreated controls
      further suggest that the age related resistance, which is acquired, targets
      increasing numbers of parasite stages as this resistance matures. Further, there
      is no evidence for an immune mediated acquisition of hypobiotic L3.

PMID- 9561710
TI  - Toxocara canis infection in the paratenic host: a study on the
      chemosusceptibility of the somatic larvae in mice.
AB  - A research on formulation and dosage strategies of anthelmintics have been
      conducted in mice experimentally infected with eggs of Toxocara canis. Multidose
      treatments commenced at days 2, 14, 81, 87 and 123 postinfection. Results
      indicated no detectable difference in the chemosusceptibility of the migrating
      early infection larvae and the resting hypobiotic chronic infection larvae.
      Application of medicated dry food (pellets) may be a simple way of improving
      efficacy of treatment compared to oral drenching. The larvicidal potential of
      fenbendazole (FBZ), albendazole (ABZ), flubendazole (FUBZ), oxibendazole (OBZ)
      and ivermectin was assessed. Reductions of 84.2 to 99.7 or 88.8 to 100% of group
      mean larval counts were recorded after 20-30-day courses of feeding pellets
      containing FBZ at 6 g kg-1 or ABZ at 1.6 g kg-1 food, respectively. Efficacies of
      57.8 to 88.2 or 81.1 to 32.0% were achieved by 20-day courses of feeding pellets
      medicated with FUBZ and OBZ at 1.6 g kg-1 or 6.0 g kg-1 food, respectively.
      Ivermectin at various dosing regimens showed only moderate larvicidal potential.
      Efficacy rates were not closely correlated with the amount of drug taken by the
      animals. The blood-brain barrier is permeable for the anthelmintics tested, and
      the brain of mice does not provide a site promoting survival of larvae.

PMID- 9561711
TI  - Therapeutic and persistent efficacy of fipronil against Boophilus microplus
      (Acari: Ixodidae) on cattle.
AB  - Cattle infested with all parasitic life-stages of Boophilus microplus
      (Canestrini) were treated once with a pour-on formulation of fipronil at 0.25,
      0.5, or 1.0% active ingredient (AI) to determine the therapeutic efficacy.
      Additionally, cattle were infested at weekly intervals for 13 consecutive weeks
      after treatment to determine the persistent effectiveness of the three
      concentrations. Results of therapeutic efficacy of fipronil showed that with each
      increase in concentration there was a corresponding and often significant (P <
      0.05) decrease in the numbers, fecundity and fertility of engorged females. The
      overall control of the Index of Reproduction (IR) achieved at 0.25 and 0.5% AI
      was 86.2 and 94.3%, respectively, while the control of the IR at the 1.0% AI
      concentration was 99.7%. The persistent efficacy of fipronil, like the
      therapeutic efficacy, was also dose related. The 0.25% AI treatment failed to
      provide complete protection (100%) against larval reinfestation, although control
      of the IR remained high (> 95%) for the first 6 weeks after treatment. In
      contrast, at 0.5% AI the control of the IR remained at 100% for the first 4 weeks
      after treatment, and was > 90% for an additional 2 weeks (6 weeks posttreatment).
      The 1.0% AI concentration afforded the longest residual activity, providing
      virtually 100% protection against larval reinfestation for 8 weeks after
      treatment was applied. Based on the results, neither the 0.25 or 0.5% AI
      concentration completely eliminated the immature stages of the tick (nymphs and
      larvae) on the host at the time of treatment (therapeutic efficacy), and the
      residual activity (persistent efficacy) did not prevent reinfestation by larvae
      for long periods after treatment. While the 1.0% AI concentration provided both
      therapeutic and residual efficacy that would be suitable for use in the
      eradication program, caution is still warranted because a few engorged females
      detached for up to 25 days after treatment, although none reproduced after the
      6th day.

PMID- 9561712
TI  - Experimental transmission of Ehrlichia canis (Rickettsiales: Ehrlichieae) by
      Dermacentor variabilis (Acari: Ixodidae).
AB  - Four trials were conducted in which laboratory-reared Dermacentor variabilis
      nymphs were exposed to Ehrlichia canis by feeding on experimentally infected dogs
      as soon as classical morulae were detected in peripheral blood monocytes. After
      molting 25, 50 or 90 adult tick pairs were permitted to feed on 7 Ehrlichia-naive
      dogs. Transmission occurred in trials 1 (1/1 dog), 3 (1/1 dog) and 4 (2/2 dogs)
      but not in trial 2 (0/3 dogs), with 4 of 7 dogs becoming infected. Successful
      transstadial transmission was demonstrated by detection of morulae in peripheral
      blood lymphocytes and by seroconversion to Ehrlichia canis 30 d post-exposure.
      Incubation periods ranged between 17 and 22 days (mean = 19). Clinical signs,
      typical of ehrlichiosis, included mucopurulent ocular discharge, lymphadenopathy
      and malaise with accompanying pyrexia, leukopenia and thrombocytopenia. Pyrexia,
      thrombocytopenia and erythrophagocytosis and vacuolization of the cytoplasm of
      monocytic cells were observed 1-4 d prior to detection of morulae. This is the
      first demonstration that a tick other than Rhipicephalus sanguineus is capable of
      transstadial transmission of this important pathogen of dogs.

PMID- 9561713
TI  - Effects of azadirachtin on Ctenocephalides felis in the dog and the cat.
AB  - Azadirachtin-containing neem seed extract is a powerful insect growth regulator,
      a feeding deterrent and repellent with low toxicity. Unfortunately, azadirachtin
      degrades rapidly in light, excessive heat or alkalinity. Evaluations of
      azadirachtin on ectoparasites on animals have been scarce. The purpose of this
      work was to describe the effects of normal and potentiated azadirachtin on
      Ctenocephalides felis in the dog or cat. Groups of kennelled greyhounds and
      domestic cats infested with C. felis were sprayed once with azadirachtin
      containing neem seed extract with or without diethyltoluamide (Deet) and/or
      citronella. Methanolic extracts with 200, 1000 or 2400 ppm azadirachtin reduced
      fleas in a dose-dependent manner. Compared with fleas counted on treated dogs
      just before treatment and untreated infested dogs, 1000-2400 ppm azadirachtin
      reduced fleas 93-53% for 19 days. However, combined with 500 ppm Deet and 33% w/v
      citronella, only 500 ppm azadirachtin reduced fleas 95-62% for 20 days. On cats
      inoculated with 50 fleas 2 days before treatment, the combination reduced fleas
      and eggs 100% to day 6 and 83-51% from day 7 to 9. On petri dishes, the
      combination achieved 100% egg mortality up to day 7 and 80% to day 14 and 48-52%
      to days 21-28. Deet, with or without neem seed extract or citronella, and
      citronella, with or without neem, did not reduce fleas significantly. The results
      show that azadirachtin reduced fleas in a dose-dependent manner in flea
      contaminated environments. In cats, the combination killed most fleas within 24
      h, providing effective flea control for 7 days. The results suggest that Deet
      with citronella potentiated the effect of azadirachtin on C. felis.

PMID- 9561714
TI  - Antibody response to Hepatozoon canis in experimentally infected dogs.
AB  - Canine hepatozoonosis is a disease caused by the tick-borne protozoan Hepatozoon
      canis. Five puppies were inoculated by ingestion of Rhipicephalus sanguineus
      ticks experimentally infected with H. canis, and all became infected with H.
      canis: gametocytes were detected in blood smears from four dogs and schizonts
      were observed in the spleen and bone marrow of the fifth. Antibodies reactive
      with H. canis gametocytes were detected by the indirect fluorescent antibody test
      (IFA), with IgM detected initially in all dogs 16 to 39 days post infection (PI)
      and IgG 22 to 43 days PI. The presence of gametocytes was first observed within
      peripheral blood neutrophils in Giemsa-stained blood smears between days 28 and
      43 PI. Gametocyte-reactive antibodies were detected before the appearance of
      blood gametocytes in three of the four parasitemic dogs and also in a dog with no
      observed parasitemia. The detection of serum antibodies prior to the detection of
      blood gametocytes, or without apparent parasitemia, suggests that antibodies
      reactive with gametocytes may be formed against earlier forms of the parasite
      developing in the parenchymal tissues. Sera of dogs experimentally infected with
      Babesia canis, Babesia gibsoni and Ehrlichia canis exhibited no reactivity when
      tested with H. canis antigen. Additionally, sera positive for H. canis were not
      reactive with antigens of Toxoplasma gondii, Neospora caninum, Leishmania
      donovani and E. canis. In conclusion, incoculation of dogs with ticks infected
      with H. canis results in production of antibodies reactive with peripheral blood
      gametocytes. Detection of IgG titres would be beneficial for the diagnosis of
      progressive infections with undetectable parasitemia, for seroprevalence studies,
      and as an adjunct to IgM titres in early infections.

PMID- 9561715
TI  - Neosporosis-associated bovine abortion in Pennsylvania.
AB  - Neospora caninum was found in fetal tissues of 34 of 688 cases of bovine abortion
      submitted to the Pennsylvania Animal Diagnostic Laboratory System during the
      period from May 1994 to November 1996. The aborted fetuses ranged in gestational
      age from 3 to 8 months. Microscopic lesions consisted primarily of encephalitis
      and myocarditis. A labeled (strept) avidin-biotin staining procedure using anti
      N. caninum polyclonal rabbit serum revealed N. caninum organisms within the fetal
      brain (27 of 27), heart (10 of 13), placenta (5 of 6), kidney (2 of 2), liver (1
      of 4) and skeletal muscle (1 of 1).

PMID- 9561716
TI  - Experimental infection of domestic sheep with culture-derived Leishmania donovani
      promastigotes.
AB  - Domestic sheep were intradermally inoculated with culture-derived stationary
      phase Leishmania donovani promastigotes. Sampling of site of inoculation, liver
      and spleen for 244 days showed that this parasite can stay alive in the skin for
      up to 28 days post-inoculation. Apart from pyrexia that was evident in all the
      animals for 42 days, no other symptoms of kala-azar were seen. No parasites were
      recovered from the visceral organs throughout the sampling period, suggesting
      that sheep are not susceptible to infection with L. donovani. It is therefore
      unlikely that sheep can be synanthropic reservoirs for this parasite.

PMID- 9561717
TI  - Canine hepatozoonosis in Brazil: description of eight naturally occurring cases.
AB  - Eight cases of canine hepatozoonosis were diagnosed at the Veterinary Hospital
      (Faculdade de Medicina Veterinaria e Zootecnia, Universidade Estadual Paulista,
      Campus de Botucatu), between October 1993 and April 1994. Clinical signs included
      anorexia, pale mucous membranes, weight loss, pain, diarrhoea, vomit, gait
      abnormalities, fever, polyuria and polydipsia. Haematologic findings revealed
      anaemia in seven cases, leucocytosis with neutrophilia in three cases,
      lymphopenia in three cases and monocytosis in four cases. Serum biochemistries
      included alterations in many parameters. The micrometry of Hepatozoon canis
      gametocytes ranged from 6.8 x 4.0 microns to 7.5 x 4.5 microns. Parasitaemia
      ranged from less than 0.5% to 2%. In all the cases reported other concurrent
      diseases were present. Diagnosis of canine hepatozoonosis was made by identifying
      H. canis gametocytes within leucocytes in stained blood smears.

PMID- 9561718
TI  - Anticancer agents. III. 4,4'-(Hexane-1,6-diyl)bis(piperazine-2,6-dione).
AB  - In the crystals of C14H22N4O4, the molecule has a crystallographic inversion
      center and the methylene chain is fully extended.

PMID- 9561719
TI  - Structure and reactivity of water at biomaterial surfaces.
AB  - Molecular self association in liquids is a physical process that can dominate
      cohesion (interfacial tension) and miscibility. In water, self association is a
      powerful organizational force leading to a three-dimensional hydrogen-bonded
      network (water structure). Localized perturbations in the chemical potential of
      water as by, for example, contact with a solid surface, induces compensating
      changes in water structure that can be sensed tens of nanometers from the point
      of origin using the surface force apparatus (SFA) and ancillary techniques. These
      instruments reveal attractive or repulsive forces between opposing surfaces
      immersed in water, over and above that anticipated by continuum theory (DLVO),
      that are attributed to a variable density (partial molar volume) of a more-or
      less ordered water structure, depending on the water wettability (surface energy)
      of the water-contacting surfaces. Water structure at surfaces is thus found to be
      a manifestation of hydrophobicity and, while mechanistic/theoretical
      interpretation of experimental results remain the subject of some debate in the
      literature, convergence of experimental observations permit, for the first time,
      quantitative definition of the relative terms 'hydrophobic' and 'hydrophilic'. In
      particular, long-range attractive forces are detected only between surfaces
      exhibiting a water contact angle theta > 65 degrees (herein defined as
      hydrophobic surfaces with pure water adhesion tension tau O = gamma O cos theta <
      30 dyn/cm where gamma O is water interfacial tension = 72.8 dyn/cm). Repulsive
      forces are detected between surfaces exhibiting theta < 65 degrees (hydrophilic
      surfaces, tau O > 30 dyn/cm). These findings suggest at least two distinct kinds
      of water structure and reactivity: a relatively less-dense water region against
      hydrophobic surfaces with an open hydrogen-bonded network and a relatively more
      dense water region against hydrophilic surfaces with a collapsed hydrogen-bonded
      network. Importantly, membrane and SFA studies reveal a discrimination between
      biologically-important ions that preferentially solubilizes divalent ions in more
      dense water regions relative to less-dense water regions in which monovalent ions
      are enriched. Thus, the compelling conclusion to be drawn from the collective
      scientific evidence gleaned from over a century of experimental and theoretical
      investigation is that solvent properties of water within the interphase
      separating a solid surface from bulk water solution vary with contacting surface
      chemistry. This interphase can extend tens of nanometers from a water-contacting
      surface due to a propagation of differences in self association between vicinal
      water and bulk-phase water. Physicochemical properties of interfacial water
      profoundly influence the biological response to materials in a surprisingly
      straightforward manner when key measures of biological activity sensitive to
      interfacial phenomena are scaled against water adhesion tension tau O of
      contacting surfaces. As examples, hydrophobic surfaces (tau O < 30 dyn/cm)
      support adsorption of various surfactants and proteins from water because
      expulsion of solute from solution into the interphase between bulk solid and
      solution phases is energetically favorable. Adsorption to hydrophobic surfaces is
      driven by the reduction of interfacial energetics concomitant with replacement of
      water molecules at the surface by adsorbed solute (surface dehydration).
      Hydrophilic surfaces (tau O > 30 dyn/cm) do not support adsorption because this
      mechanism is energetically unfavorable. Protein-adsorbing hydrophobic surfaces
      are inefficient contact activators of the blood coagulation cascade whereas
      protein-repellent hydrophilic surfaces are efficient activators of blood
      coagulation. Mammalian cell attachment is a process distinct from protein
      adsorption that occurs efficiently to hydrophilic surfaces but inefficiently to
      hydrophobic surfaces. (ABSTRACT TRUNCATED)

PMID- 9561720
TI  - Biopathological crystallization: a general view about the mechanisms of renal
      stone formation.
AB  - A general classification of most common renal calculi (calcium oxalate, phosphate
      and uric acid stones) based on their formation mechanism is presented. The main
      etiological factors that enable their development are discussed considering
      present knowledge of calcium oxalate, insoluble urinary phosphates and uric acid
      crystallization and the fine structure of respective renal stones. Considering
      the formation mechanisms of the discussed calculi, common aspects permit us to
      distinguish two general mechanisms of calculi formation: development of calculi
      attached to papillary epithelium and development of calculi in cavities without
      any attachment to urothelium.

PMID- 9561721
TI  - Supramolecular organization of the subsarcolemmal cytoskeleton of adult skeletal
      muscle fibers. A review.
AB  - This review is focused on the composition and organization of the junctional
      subsarcolemmal cytoskeleton of adult muscle fibers. The cytoskeleton of muscle
      fibers is organized in functionally distinct compartments and the subsarcolemmal
      cytoskeleton itself can be broadly divided into junctional (myotendinous
      junction, neuromuscular junction and costameres) and non-junctional domains. In
      junctional zones three different multimolecular cytoskeletal complexes coexist:
      the focal adhesion-type, the spectrin-based and the dystrophin vs utrophin-based
      membrane skeleton systems. These complexes extend over several levels, from
      intracytoplasmic to subsarcolemmal and transmembranous; their common feature is
      the anchorage of actin filaments emanating from the intracytoplasmic level. The
      different cytoskeletal proteins, their putative roles and their interactions with
      various signaling pathways are presented here in detail. The subsarcolemmal
      cytoskeleton complexes are thought to play distinct physiological roles (membrane
      stabilization, force transmission to extracellular matrix, ionic channel
      anchorage, etc) but their colocalization on the three sarcolemmal junctional
      domains strongly suggests interrelated or common functions.

PMID- 9561722
TI  - Paracrine effect of seminiferous tubule factors on rat Leydig cell testosterone
      production: role of cytoskeleton.
AB  - In Percoll purified Leydig cells from mature rat we have demonstrated that the
      basal testosterone production (9.5 ng/10(6) Leydig cells/24 h) is increased 10
      fold in presence of a saturating amount of hCG (1 IU/mL) and diminished in a dose
      related manner when larger concentrations of gonadotropin are used to reach 14
      ng/10(6) Leydig cells for 50 IU of hCG. If 40% (v/v) seminiferous tubule medium
      (STM) is added together with hCG (1 IU/mL) to the incubation medium, a further
      increase (62%) of testosterone output is noticed. Obviously, when the
      testosterone production is low as a consequence of a higher dose of hCG (50
      IU/mL), the STM (80%) improves the steroid synthesis five-fold (67.4 ng).
      Concerning the cytoskeletal components (microtubules, intermediate filaments and
      microfilaments) which have been examined in presence or absence of hCG and STM,
      we have found a rearrangement of cytoskeletal elements as well as cell-shape
      changes in relation with hormonal activity of the cells. The most prominent
      alterations of cytoskeletal elements have been observed after 24 h of incubation
      with 1 IU/mL of hCG added together with 80% of STM. The obtained results suggest
      that paracrine factor(s) presents in STM and acting in synergy with LH/hCG
      generate(s) the rearrangement of cytoskeletal structures which, in turn,
      facilitates the availability of cholesterol for the mitochondria and finally
      enhances the testosterone production in the rat Leydig cells.

PMID- 9561723
TI  - Monitoring of effector and target cell stimulation during conjugation by
      fluorescence polarization.
AB  - The aim of the present study was to trace early intracellular changes induced in
      effector and target cells during their conjugation. This was performed by
      monitoring the intracellular fluorescein fluorescence polarization (IFFP), using
      the Cellscan apparatus. This apparatus permits the repetitive spectroscopic
      measurement of individual selected live cells within a population of many cells,
      while the location of each cell is known and preserved during the various cell
      manipulations and/or their suspending medium. Both natural killer (NK) and
      lymphocyte activated killer (LAK) cells were used as effector cells, while NK
      sensitive K562 and NK-resistant Daudi cell lines were used as targets. In this
      study kinetic IFFP measurements were carried out for a period of approximately 4
      h following cell attachment. Within minutes following effector-target
      conjugation, transient reduction of IFFP was observed consecutively, first in the
      effector and then in the target cells. A continuous reduction of IFFP occurring
      only in target cells was also found 50 min following conjugation. No reduction in
      IFFP was observed using NK- and LAK-resistant target cells. Good correlation was
      found between early stages of conjugation, as assessed by IFFP, and cytolytic
      efficiency as assessed by 51chromium release assay. When NK-resistant and LAK
      resistant target cells were used, no reduction of IFFP was observed.

PMID- 9561724
TI  - Characterization of morphogenetic and invasive abilities of human mammary
      epithelial cells: correlation with variations of urokinase-type plasminogen
      activator activity and type-1 plasminogen activator inhibitor level.
AB  - Urokinase-type plasminogen activator (uPA) and one of its inhibitors, the PAI-1,
      are involved in the proteolytic cascade of matrix degradation during in vivo
      morphogenesis or metastasis. In the present study, we have characterized the in
      vitro morphological behavior of human normal and malignant mammary epithelial
      cells and determined the levels of uPA activity and PAI-1 during these events.
      Two-dimensional cultures in the presence of inductive fibroblast-conditioned
      medium (CM) allowed migration of HBL-100 cells and MDA-MB-231 cells. Normal human
      mammary epithelial cells (HMEC) and MCF-7 cells failed to migrate under these
      conditions. The epithelial cell migration correlated with an increase in the uPA
      activity whereas their immobility correlated with both increases in uPA activity
      and PAI-1 level. In three-dimensional cultures in collagen gel, fibroblasts or
      fibroblast CM induced branching tubular morphogenesis to HMEC, cord-like
      extensions to HBL-100 cells and a greater invasiveness ability to MDA-MB-231
      cells. These events correlated with an increased uPA activity. In contrast, no
      morphological rearrangement was observed in MCF-7 cells and this correlated with
      both increases in uPA activity and PAI-1 level. Altogether, these results show
      that the in vitro mammary epithelial behavior is under the influence of
      mesenchymal inductive signals and is in agreement with modifications of uPA
      activity and PAI-1 levels. Our culture system gives a suitable model to study the
      mechanisms of mammary development and metastasis and to highlight the involvement
      of proteases and their inhibitors in cell-cell positioning and cell-matrix
      reorganization.

PMID- 9561725
TI  - Lack of modulation of the galectin-3 and asialoglycoprotein receptor
      transcription in hepatocarcinoma of transgenic mice.
AB  - Galectin-3 and asialoglycoprotein receptor are lectins belonging to the classes
      of soluble lectins and of membrane C type lectins respectively. Conflicting
      results have been reported concerning their transcription level in the time
      course development of tumours. In the present study we investigated the
      abnormalities and the transcription levels of galectin-3 and asialoglycoprotein
      receptor genes in liver-targeted SV40 large T transgenic mice related to normal
      mice. In the strain expressing the highest level of large T, 100% of the male
      mice reproducibly developed an hepatocarcinoma. We provide evidence that the
      galectin-3 and asialoglycoprotein receptor genes are stable in such mice. The
      galectin-3 gene is weakly transcribed and its level is identical and constant in
      normal and transgenic mice, suggesting a lack of involvement in the development
      of large T-induced hepatocarcinoma. The asialoglycoprotein receptor gene is
      actively transcribed and its level remains high all along the development of the
      tumour; therefore, in such an hepatocarcinoma the asialoglycoprotein receptor
      could be used to take up drugs, genes or oligonucleotides associated with
      glycosylated carriers bearing galactose residues in a terminal non-reducing
      position.

PMID- 9561726
TI  - An Escherichia coli ccm (cytochrome c maturation) deletion strain substantially
      expresses Hydrogenobacter thermophilus cytochrome c552 in the cytoplasm:
      availability of haem influences cytochrome c552 maturation.
AB  - The maturation of Hydrogenobacter thermophilus cytochrome c552 in the cytoplasm
      of Escherichia coli is unique among bacterial c-type cytochromes. It is now shown
      to be matured in a strain lacking the whole set of ccm (cytochrome c maturation)
      genes that are normally required for c-type cytochrome biogenesis in E. coli. As
      this cytochrome is thermostable we propose that the apocytochrome c552 has
      sufficient tertiary structure to allow the haem to slot into its binding pocket,
      which in turn triggers the spontaneous covalent attachment between apocytochrome
      c552 and haem. The ccm deletion strain of E. coli, derived from a strain that
      synthesizes elevated levels of endogenous c-type cytochromes, also produces
      larger amounts of cytoplasmic H. thermophilus cytochrome c552 than a reference
      strain. This implies that elevated production of c-type cytochromes is not a
      consequence of high activity of ccm genes but rather an enhanced ability to
      supply haem, a view that is supported by the increase in thermophilic cytochrome
      c552 biogenesis that occurs in a reference strain following supplementation of
      growth media with delta-aminolevulinic acid.

PMID- 9561728
TI  - Tyrosine phosphate hydrolysis of host proteins by Trypanosoma cruzi is linked to
      cell invasion.
AB  - Invasion of cultured L6E9 myoblasts by Trypanosoma cruzi induced tyrosine
      dephosphorylation of proteins of 234, 205, and 50 kDa. Invasion was greatly
      reduced in the presence of the protein tyrosine phosphate inhibitors sodium o
      vanadate and zinc chloride, and in the presence of excess phosphotyrosine or p
      nitrophenyl phosphate, but not in the presence of excess phosphoserine or
      phosphothreonine. These results suggest an important role for protein tyrosine
      dephosphorylation in the invasion of host cells by T. cruzi.

PMID- 9561729
TI  - Lack of protection following immunisation with H. pylori outer membrane vesicles
      highlights antigenic differences between H. felis and H. pylori.
AB  - Helicobacter pylori-induced inflammation is associated with the development of
      gastritis, peptic ulcer disease and gastric cancer in humans. Immunisation
      against this bacterium would ultimately have a major impact on H. pylori-related
      disease, notably global gastric cancer rates. To date, several potential H.
      pylori vaccine candidates have been identified. In this study, the Helicobacter
      felis/murine model was used to assess the immunogenicity of a previously
      undescribed H. pylori outer membrane vesicle fraction in immune protection.

PMID- 9561727
TI  - Histidine utilisation operon (hut) is upregulated at low temperature in the
      antarctic psychrotrophic bacterium Pseudomonas syringae.
AB  - The antarctic psychrotrophic bacterium Pseudomonas syringae was mutagenised using
      a transposon Tn5-OT182 which facilitates identification of promoter fusions
      expressing the reporter gene (lacZ) for beta-galactosidase. Most mutants
      expressed beta-galactosidase both at optimal growth temperature (20-22 degrees C)
      and at low temperature (4 degrees C). But a small percentage of the mutants
      (approximately 5%) were unique in that they expressed beta-galactosidase activity
      predominantly at low temperature. One such mutant was found to have an insertion
      in the gene for urocanase (hutU) of the histidine utilisation (hut) operon.
      Direct assay of urocanase and histidase activity in wild-type cells of various
      antarctic psychrotrophic strains including P. syringae, P. fluorescens and P.
      putida also suggested that the hut operon is expressed at an elevated level at
      low temperature.

PMID- 9561730
TI  - A novel phenol hydroxylase and catechol 2,3-dioxygenase from the thermophilic
      Bacillus thermoleovorans strain A2: nucleotide sequence and analysis of the
      genes.
AB  - The new thermophilic Bacillus thermoleovorans strain A2 degrades phenol and
      cresols via the meta cleavage pathway. The first two enzymes involved in this
      process, the phenol hydroxylase and catechol 2,3-dioxygenase, encoded by the pheA
      and pheB genes respectively, were cloned and sequenced. The deduced amino acid
      sequence of pheA contains 524 amino acids with a theoretical M(r) of 59,602 Da
      and displays less than 10% amino acid identity to known phenol hydroxylases. The
      greatest amino acid identity (54%) displayed by pheA is with the larger component
      of the two-component 4-hydroxyphenylacetic acid hydroxylase from Escherichia coli
      W encoded by hpaB. No second component was present on the 3.8-kb insert. The
      consensus sequence GXGXXG for FAD/NAD binding sites is not present in pheA. PheB
      encodes a new catechol 2,3-dioxygenase of 308 amino acids (M(r) 35,487 Da) which
      has greatest amino acid identity (43%) with the 3-methyl catechol 2,3-dioxygenase
      of Pseudomonas putida UCC2 encoded by tdnC. Both pheA and pheB encode new enzymes
      which display low sequence homology with those previously published.

PMID- 9561731
TI  - The Bradyrhizobium japonicum phoB gene is required for phosphate-limited growth
      but not for symbiotic nitrogen fixation.
AB  - We identified by cloning and DNA sequence analysis the phosphate regulatory gene
      phoB of Bradyrhizobium japonicum. The deduced gene product displayed pronounced
      similarity to the PhoB protein of Sinorhizobium meliloti (71.4% identical amino
      acids). Escherichia coli (50.2%) and other bacterial species. Insertion of a
      kanamycin resistance cassette into phoB led to impaired growth of the B.
      japonicum mutant in media containing approximately 25 microM phosphate or less. A
      standard plant infection test using wild-type and phoB-defective B. japonicum
      strains showed that the phoB mutation had no effect on the symbiotic properties
      of B. japonicum with its soybean host plant.

PMID- 9561732
TI  - Conversion of the coprogen transport protein FhuE and the ferrioxamine B
      transport protein FoxA into ferrichrome transport proteins.
AB  - The FhuA protein of Escherichia coli K-12 transports ferrichrome and the
      structurally related antibiotic albomycin across the outer membrane and serves as
      a receptor for the phages T1, T5, and phi 80 and for colicin M. In this paper, we
      show that chimeric proteins consisting of the central part of FhuA and the N- and
      C-terminal parts of FhuE (coprogen receptor) or the N- and/or C-terminal parts of
      FoxA (ferrioxamine B receptor), function as ferrichrome transport proteins.
      Although the hybrid proteins contained the previously identified gating loop of
      FhuA, which is the principal binding site of the phages T5, T1, and phi 80, only
      the hybrid protein consisting of the N-terminal third of FoxA and the C-terminal
      two thirds of FhuA conferred weak phage sensitivity to cells. Apparently, the
      gating loop is essential, but not sufficient for wild-type levels of ferrichrome
      transport and for phage sensitivity. The properties of FhuA-FoxA hybrids suggest
      different regions of the two receptors for ferric siderophore uptake.

PMID- 9561733
TI  - Vi-deficient and nonfimbriated mutants of Salmonella typhi agglutinate human
      blood type antigens and are hyperinvasive.
AB  - We generated nonfimbriated mutants from both Vi-positive and -negative Salmonella
      typhi to analyze the role of type 1 fimbriae and Vi-antigen in bacterial
      invasion. A Vi-defective mutant of S. typhi GIFU 10007-3 was more invasive than
      the wild-type strain GIFU 10007. The wild-type strain expressing Vi-antigen did
      not agglutinate both Saccharomyces cerevisiae and human erythrocytes but Vi
      defective mutants were able to agglutinate S. cerevisiae and human erythrocytes.
      Nonfimbriated mutants from Vi-negative GIFU 10007-3 lost the ability to adhere to
      S. cerevisiae but still could agglutinate human erythrocytes. The Vi-negative
      mutant increased secreted proteins and became 5-fold more invasive than the wild
      type strain. Nonfimbriated Vi mutants became 50-120-fold more invasive than the
      wild-type GIFU 10007. To determine why nonfimbriated Vi mutants still agglutinate
      human red blood cells, we searched bacterial proteins that could bind human blood
      type antigens. We finally identified a candidate 37 kDa outer membrane protein
      that recognized fucosyl-galactose, a structure common to blood type A, B and H
      antigens.

PMID- 9561734
TI  - Recovery and phylogenetic analysis of archaeal rRNA sequences from continental
      shelf sediments.
AB  - Phylogenetic analyses of archaeal 16S rRNA genes (rDNA) from DNA extracted from
      continental shelf sediments revealed the presence of two major lineages,
      belonging to the kingdoms Crenarchaeota and Euryarchacota, respectively. Our
      analyses indicate that the benthic Archaea belong to a new group, divergent from
      the marine low-temperature planktonic Archaea. This is the first report showing
      the existence of Archaea, unrelated to methanogens, specifically associated with
      low-temperature anoxic marine sediments.

PMID- 9561735
TI  - Phylogenetic relationships of Salmonella based on DNA sequence comparison of atpD
      encoding the beta subunit of ATP synthase.
AB  - DNA sequences covering 57% of atpD encoding the beta subunit of ATP synthase were
      determined for 16 strains of Salmonella enterica, two strains of S. bongori, and
      one strain each of Citrobacter freundii and Yersinia enterocolitica, and
      comparison was made with the published Escherichia coli and Enterobacter
      aerogenes sequences. The phylogenetic tree based on maximum-likelihood analysis
      showed separation of the subspecies of S. enterica except for two serotypes of
      subspecies II which were unsupported by a common node. The two serotypes of S.
      bongori were separated from S. enterica and related to the serotypes of
      subspecies II. A tight relationship was found between S. enterica subspecies IIIa
      consisting of monophasic serotypes and subspecies IIIb consisting of diphasic
      serotypes. This is in conflict with results obtained for most other housekeeping
      genes and the 23S rRNA gene separating mono- from diphasic subspecies.

PMID- 9561736
TI  - Rapid species identification within two groups of closely related lactobacilli
      using PCR primers that target the 16S/23S rRNA spacer region.
AB  - A rapid and reliable PCR-based method for distinguishing closely related species
      within two groups of lactobacilli is described. Primers complementary to species
      specific sequences in the 16S/23S rDNA spacer regions were designed after
      sequencing and sequence comparison of the spacer regions of 32 strains. The
      strains belong to two groups of closely related Lactobacillus species; one
      composed of Lactobacillus curvatus, Lactobacillus graminis and Lactobacillus
      sake, the other of Lactobacillus paraplantarum, Lactobacillus pentosus and
      Lactobacillus plantarum. PCR assays with the designed primers and subsequent
      agarose gel analysis of the amplified fragments allowed the same species
      identification as the DNA/DNA hybridization procedure.

PMID- 9561737
TI  - A new theta-type thermosensitive replicon from Lactococcus lactis as an
      integration vector for Enterococcus faecalis.
AB  - We isolated a replication thermosensitive mutant of the theta-type lactococcal
      pUCL22 replicon. An improved version of this thermosensitive replicon was
      obtained by fusioning the replication repA gene with the downstream repB gene.
      The resulting plasmid was named pUCB3522Ts. It is highly instable at 42 degrees C
      in Enterococcus faecalis. Integration into the chromosome via homologous
      recombination was monitored using the npr gene of E. faecalis JH2-2 as a target.
      A 513 bp PCR amplification product from an internal region of this npr gene was
      cloned into pUCB3522Ts. Integration of this construction into the JH2-2 npr gene
      was selected by shift temperature, from 30 degrees C to 42 degrees C. 85% of the
      analysed clones showed integration into the npr gene, demonstrating the
      practicality of this thermosensitive replicon as a genetic integrative tool for
      E. faecalis.

PMID- 9561738
TI  - Cloning and expression of an iron-containing superoxide dismutase in the
      parasitic protist, Trichomonas vaginalis.
AB  - A superoxide dismutase (SOD) gene of the parasitic protist Trichomonas vaginalis
      was cloned, sequenced, expressed in Escherichia coli, and its gene product
      characterized. It is an iron-containing dimeric protein with a monomeric mass of
      22,067 Da. Southern blots analyses suggested the presence of seven iron
      containing (FeSOD) gene copies. Hydrophobic cluster analysis revealed some
      peculiarities in the 2D structure of the FeSOD from T. vaginalis and a strong
      structural conservation between prokaryotic and eukaryotic FeSODs. Phylogenetic
      reconstruction of the SOD sequences confirmed the dichotomy between FeSODs and
      manganese-containing SODs. FeSODs of protists appeared to group together with
      homologous proteobacterial enzymes suggesting a possible origin of eukaryotic
      FeSODs through an endosymbiotic event.

PMID- 9561739
TI  - Presence of integrons in isolates of different biotypes of Acinetobacter
      baumannii from Chilean hospitals.
AB  - Class 1 and class 2 integrons were investigated by hybridisation in 100 isolates
      of multiresistant biotypes of Acinetobacter baumannii from Chilean hospitals.
      Most isolates of A. baumannii biotype 9, the prevalent biotype, harboured
      integrons of class 2 (Tn7-like) whereas no integrons were detected in infrequent
      biotypes. Integron-carrying isolates exhibited broader antibiotic resistance
      patterns as well as higher resistance levels to various antimicrobials.

PMID- 9561740
TI  - General transducing phages like Salmonella phage P22 isolated using a smooth
      strain of Escherichia coli as host.
AB  - A smooth colony strain, resistant to phages lambda and P22, was isolated from
      sewage and identified as Escherichia coli (strain H). Four temperate phages
      plaquing on strain H were isolated from sewage. The archetype, HK620, does not
      plaque on strains C and K12 of E. coli nor on the LT2 strain of Salmonella
      enterica. Bacterial mutants resistant to a clear plaque mutant of HK620 produce
      rough colonies. Some are also galactose-negative, a few are histidine auxotrophs,
      and most show sensitivity to lambda. HK620 can transduce a wide variety of
      auxotrophic mutants of E. coli H to prototrophy. It can recombine with lambda but
      its virions resemble those of P22.

PMID- 9561741
TI  - Phosphatase activity and lead resistance in Citrobacter freundii and
      Staphylococcus aureus.
AB  - It has been previously reported that strains of Citrobacter freundii and of
      Staphylococcus aureus accumulated lead as Pb-phosphate when grown on media
      supplemented with high levels of lead salts. Phosphatase activity, which has been
      postulated to be involved in lead accumulation, was unrelated to lead resistance,
      resistant and sensitive cells displaying similar levels and patterns of enzyme
      activity.

PMID- 9561742
TI  - A specific alkaline phosphatase from Saccharomyces cerevisiae with protein
      phosphatase activity.
AB  - In this paper, specific PHO13 alkaline phosphatase from Saccharomyces cerevisiae
      was demonstrated to possess phosphoprotein phosphatase activity on the
      phosphoseryl proteins histone II-A and casein. The enzyme is a monomeric protein
      with molecular mass of 60 kDa and hydrolyzes p-nitrophenyl phosphate with maximal
      activity at pH 8.2 with strong dependence on Mg2+ ions and an apparent Km of 3.6
      x 10(-5) M. No other substrates tested except phosphorylated histone II-A and
      casein were hydrolyzed at any significant rate. These data suggest that the
      physiological role of the p-nitrophenyl phosphate-specific phosphatase may
      involve participation in reversible protein phosphorylation. 1988 Federation of
      European Microbiological Societies.

PMID- 9561743
TI  - Growth phase-dependent active transport of pyridoxine in a fission yeast,
      Schizosaccharomyces pombe.
AB  - Schizosaccharomyces pombe showed maximum pyridoxine uptake activity around 10 h
      after starting cultivation. High concentrations of thiamine and pyridoxine in the
      medium did not affect the activity or the time but changed intracellular levels
      of vitamin B6 compounds. Pyridoxine was taken up by a saturable mechanism with
      two kinds of affinity (K(m) 22.4 microM and 118 microM). The uptake depended on
      the energy produced anaerobically with an optimum pH of 4.5. The uptake was
      completely inhibited by amiloride, sodium azide or 2,4-dinitrophenol. The uptake
      system of the fission yeast was different in various respects from that of a
      budding yeast.

PMID- 9561744
TI  - Sporulation and time course expression of sigma-factor homologous genes in
      Clostridium acetobutylicum.
AB  - The gene for the vegetative sigma factor A of Clostridium acetobutylicum was
      constitutively transcribed during growth and formed an operon together with dnaE.
      Sporulation-specific sigma factors E, G, and K were sequentially induced shortly
      before mature endospores could be detected. Maximal transcription in the course
      of spore formation was found to be in the order sigE-sigG-sigK, thus matching the
      pattern described for Bacillus subtilis. From primer extension experiments
      promoter structures could be deduced with high homology to the Bacillus
      consensus. Upstream of the spoIIGA-sigE operon a gene with significant similarity
      to ftsZ could be detected.

PMID- 9561745
TI  - Characterization of new insertion-like sequences of Enterococcus hirae and their
      dissemination among clinical Enterococcus faecium isolates.
AB  - Sequence analysis of different fragments that hybridized with a 4.5-kb EcoRI
      fragment originally cloned from Enterococcus hirae ATCC 9790 showed 66% homology
      to IS-like sequences found in staphylococci and lactococci. We tested several
      enterococcal ATCC strains and found that only E. hirae ATCC 9790 and Enterococcus
      faecium ATCC 19434 hybridized with the IS-like sequence. Moreover, we wanted to
      investigate the dissemination of this new IS among E. faecium strains. We
      analyzed 131 clinical E. faecium isolated in Italy and the USA for the presence
      of the IS and we found its presence in more than 63% of the isolates. The
      hybridization patterns obtained vary considerably between unrelated strains and
      allow further classification among ribotype-grouped species.

PMID- 9561746
TI  - Cloning and characterization of the phenylalanyl-tRNA synthetase beta subunit
      gene from Candida albicans.
AB  - A Candida albicans expression library was constructed from RNA isolated from
      regenerating protoplasts. A 1.4-kb cDNA clone was used to isolate a genomic
      fragment. Sequence analysis revealed an open reading frame of 593 amino acids
      with an overall identity of 63.6% with the phenylalanyl-tRNA synthetase beta
      subunit (FRS1) of Saccharomyces cerevisiae. We named it CaFRS1. It is located in
      a single copy in chromosome R, SfiI fragment M. Its expression showed a decrease
      during the cell wall regeneration process in protoplasts of both yeast and
      mycelial cells of C. albicans, suggesting its requirement thereof in initial
      steps of the cell wall synthesis.

PMID- 9561747
TI  - In vitro interaction of the IHF-like proteins Acinetobacter junii and Proteus
      vulgaris with ihf sites.
AB  - The ability of the IHF-like proteins of Acinetobacter junii and Proteus vulgaris
      to interact with the H' attP and pR' ihf sites of lambda DNA was investigated.
      IHF from A. junii and P. vulgaris was found to bind the examined ihf sites in a
      way similar to IHF from Escherichia coli as shown by gel mobility shift DNA
      binding assays and footprinting analysis. The three IHF proteins bound to the pR'
      ihf site that overlaps the-35 region of that promoter and in vitro repression of
      transcription by each IHF was observed. These results confirm that IHF-like
      proteins from Gram-negative bacteria can recognize the same specific DNA
      sequences and appear to be important in regulation of transcription.

PMID- 9561748
TI  - Calcium levels correlate with cell cycle phase and affect the level of the cyclin
      B transcript in Dictyostelium discoideum.
AB  - In pre-aggregation amoebae of Dictyostelium discoideum, phenotypic differences
      with respect to cellular Ca2+ and cell cycle phases are known to bias post
      aggregative cell-type choice. Using chlortetracycline fluorescence as an
      indicator, we found that cellular Ca2+ is highest at the S phase of the cell
      cycle. Upon increasing the level of Ca2+ with the help of the calcium ionophore
      A23187, there is a significant decrease in the cyclin B (clb1) mRNA level; the
      cdc2 mRNA level shows a marginal decrease. These results suggest that the effect
      of Ca2+ and the cell cycle on cell fate could be exerted at the level of
      transcription, or message stability, of specific genes.

PMID- 9561749
TI  - Salmonella typhi rpoS mutant is less cytotoxic than the parent strain but
      survives inside resting THP-1 macrophages.
AB  - Transcription of the stationary-phase sigma factor RpoS of Salmonella typhi
      increased in the macrophage. A single rpoS mutant of S. typhi was constructed to
      analyze the role of RpoS in intracellular multiplication of the bacterium and
      host cell killing. This mutant was sensitive to starvation, low pH and hydrogen
      peroxide; however, it could still multiply inside resting macrophages and was
      less cytotoxic than the wild-type strain. Therefore, S. typhi might produce RpoS
      dependent factors which could contribute to host cell death.

PMID- 9561750
TI  - Cellulase and hemicellulase genes of Clostridium thermocellum from five
      independent collections contain few overlaps and are widely scattered across the
      chromosome.
AB  - Five independent collections, comprising a total of 34 clones encoding
      cellulases, hemicellulases and cell surface proteins of Clostridium thermocellum,
      were searched for overlapping or contiguous DNA fragments. The clones were
      hybridized to large genomic restriction fragments separated by pulse-field
      electrophoresis. Clones hybridizing to the same fragment were further compared by
      hybridization to smaller fragments, by cross-hybridization and by restriction
      mapping. The probes hybridized to loci which were usually not clustered and were
      scattered over at least one third of the chromosome. Besides previously
      identified clusters, only two clones were found to be adjacent. Two pairs of
      clones appeared to contain the same genes cloned in duplicate, and one of the
      genes was shown to be cloned in triplicate.

PMID- 9561751
TI  - Substance P and related peptides in porcine cortex: whole tissue and nuclear
      localization.
AB  - A large portion of the knowledge that has been gathered on the distribution of
      neuropeptides in neural tissues is based on findings obtained with
      immunocytochemistry and radioimmunoassay. However, these methods give limited
      structural information about the peptides being studied. Using porcine cortex as
      a model tissue, we combined immunoaffinity chromatography with reversed-phase
      high-performance liquid chromatography, radioimmunoassay, and matrix-assisted
      laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). We
      determined the molecular nature of the peptides contributing to the substance P
      like immunoreactivity measured in extracts of whole tissue and cell nuclei. In
      addition to substance P(1-11), other peptides were extracted using this protocol.
      The presence of SP(1-11) was confirmed through post-source decay analysis. These
      results illustrate the usefulness of MALDI-TOF-MS in the characterization of
      neuropeptides from biological tissues.

PMID- 9561752
TI  - Molecular characterization of metal-binding polypeptide domains by electrospray
      ionization mass spectrometry and metal chelate affinity chromatography.
AB  - Metal ion-binding of synthetic peptides containing HxH and CxxC motifs was
      investigated by electrospray ionization mass spectrometry (ESI-MS) and metal
      chelate affinity chromatography. A high affinity of Ni2+ and Cu2+ to HxH
      containing sequences was found. Based on their natural metal ion-binding
      potential it was possible to include metal affinity chromatography in the
      purification process of two proteins without using an additional His-tag
      sequence: ATPase-439, a P type ATPase from Helicobacter pylori and the amyloid
      precursor protein (APP).

PMID- 9561753
TI  - Use of high-precision gas isotope ratio mass spectrometry to determine natural
      abundance 13C in lutein isolated from C3 and C4 plant sources.
AB  - A method was developed for high-precision stable carbon isotope ratio analysis of
      lutein isolated from a C3 (marigold flower) and a C4 (corn gluten meal) plant
      source using gas chromatography-combustion interfaced isotope ratio mass
      spectrometry. The natural abundance of 13C (expressed as delta 13C versus the
      international standard, Pee Dee Belemnite, in per mil units, denoted /1000) in
      lutein isolated from marigold flower and corn gluten meal was determined to be 
      29.90 +/- 0.20/1000 and -19.77 +/- 0.27/1000 (mean +/- S.D.), respectively. The
      high precision of gas isotope ratio mass spectrometry is potentially applicable
      to detect differences of isotopic composition of lutein in the blood, tissues, or
      excreta of animal models or humans that result from differences in the natural
      abundance of 13C in C3 and C4 plant foods.

PMID- 9561754
TI  - Electrospray ionization mass spectrometric and liquid chromatographic-mass
      spectrometric studies on the metabolism of synthetic dynorphin A peptides in
      brain tissue in vitro and in vivo.
AB  - Metabolic stability of synthetic dynorphins [N-terminal fragments of dynorphin A
      (Dyn A)] were evaluated in vitro and in vivo. These peptides were applied at
      concentrations 100-1000 times higher than those of the endogenous dynorphins.
      Degradation kinetics of these peptides were studied in rat brain homogenate by
      using microbore gradient RP-LC assay, and limited information on their metabolism
      was obtained by electrospray ionization mass spectrometry (ESI-MS) of the
      isolated metabolites. In vivo cerebral microdialysis, in which the peptides were
      introduced via the probe placed in striatum region of the brain of the
      experimental animals, was used to circumvent contamination arising from
      autoproteolysis of brain during incubation of the samples in vitro. Metabolites
      of Dyn A (1-13) and Dyn A (1-11) were identified from electrospray ionization
      mass spectra of the microdialysates without chromatographic separation; the
      identification of peptides in the mixtures were supported by medium resolution
      ESI Fourier-transform ion cyclotron resonance MS. LC-MS was used to fully
      characterize the complex peptide mixture obtained after the striatal perfusion of
      Dyn A (1-12).

PMID- 9561755
TI  - Nanogram scale separations of proteins using capillary high-performance liquid
      chromatography with fully-automated on-line microfraction collection followed by
      matrix-assisted laser desorption ionisation time-of-flight mass spectrometry,
      protein sequencing and western blot analysis.
AB  - Capillary HPLC was applied for highly sensitive protein separations on a nanogram
      scale. A crude extract of acid soluble proteins from maize kernels was used as a
      model extract and separated on a 300-micron I.D. reversed-phase capillary column.
      Protein fractions of 1-4 microliters volume were fully automatically collected
      with a new robot microfraction collection system. Fraction collection was
      performed onto matrix assisted laser desorption ionisation time-of-flight targets
      for mass spectrometric analysis, onto sequencing membranes for automated Edman
      degradation and onto nitrocellulose membranes for Western blot analysis.

PMID- 9561756
TI  - Liquid chromatographic-high-resolution mass spectrometric and tandem mass
      spectrometric identification of synthetic peptides using electrospray ionization.
AB  - Liquid chromatography-high-resolution electrospray mass spectrometry (LC-ESI-MS)
      was investigated for the identification of known and unknown synthetic peptides
      in a research effort designed to evaluate the applicability of this and
      complementary MS techniques for peptide characterization and identification. The
      monoisotopic molecular masses of five related peptides with molecular masses
      between 2000 and 2500 u were acquired with a resolution of 3000 (10% valley).
      Under narrow and wide mass range magnetic sector scanning conditions monoisotopic
      molecular mass errors were typically in the 10-20 and 30-40 ppm range,
      respectively. Tryptic maps were generated for each peptide following LC-ESI-MS
      analysis and collisionally activated dissociation (CAD) in the ESI interface
      resulted in the production of characteristic product ions that enabled amino acid
      sequencing of the tryptic fragments. Unknown identification was demonstrated
      during analysis of an incomplete synthetic peptide reaction mixture. The
      synthesis of an 18 amino acid peptide, LTTAVKKVLTTGLPALIS, was not successful. In
      its place were six unknown peptides that were identified on the basis of
      monoisotopic molecular mass and amino acid sequence data. The monoisotopic
      molecular masses of these unknowns were determined to within 10-20 ppm with a
      resolution of 3500 (10% valley). Amino acid sequences for the six peptides were
      generated during ESI-MS-MS analysis. Finally two synthetic peptides differing
      only by the incorporation of a 13C at leucine were analysed with a resolution of
      6000 (10% valley) to confirm that the isotopic distributions were consistent with
      theoretical expectations.

PMID- 9561757
TI  - Determination of indole-3-pyruvic acid levels in Arabidopsis thaliana by gas
      chromatography-selected ion monitoring-mass spectrometry.
AB  - A rapid and simple method is described for the determination of indole-3-pyruvic
      acid (IPA) levels in Arabidopsis thaliana by gas chromatography-selected ion
      monitoring-mass spectrometry (GC-SIM-MS). The method includes derivatization of
      IPA with hydroxylamine in the crude extract, followed by ethyl acetate
      partitioning, solid-phase extraction with C18 resin, reversed-phase high
      performance liquid chromatography (HPLC), and GC-SIM-MS. Three derivatizing
      reagents were tested; these were pentafluorobenzylhydroxylamine,
      pentafluorophenylhydrazine, and hydroxylamine. Hydroxylamine proved to be the
      most useful, as the IPA-oxime was easiest to purify from plant extracts and was
      the most stable. IPA was quantified in Arabidopsis seedlings ranging in age from
      5 to 12 days; levels varied from 4 to 13 ng/g, peaking at 7-9 days.

PMID- 9561758
TI  - Development of a method based on liquid chromatography-electrospray mass
      spectrometry for analyzing imidazolinone herbicides in environmental water at
      part-per-trillion levels.
AB  - An evaluation was made of the feasibility of using reversed-phase liquid
      chromatography-mass spectrometry with an electrospray interface (LC-ESI-MS) to
      measure traces of imidazolinone herbicides in different natural water samples.
      The imidazolinones are a significant new class of low-use-rate, reduced
      environmental-risk herbicides for the protection of a wide variety of
      agricultural commodities. The procedure used involved passing 0.5, 1, 2 1 of
      river, ground and drinking water samples, respectively, through a 0.5 g
      graphitized carbon black (GCB) extraction cartridge. Analytes were eluted from
      the GCB surface by 8 ml of a methylene chloride-methanol (80:20, v/v) solution
      acidified with formic acid, 25 mM. Recovery was higher than 89% irrespective of
      the aqueous matrix in which the analytes were dissolved. A conventional 4.6 mm
      I.D. reversed-phase LC C18 column operating with a mobile phase flow-rate of 1
      ml/min was used to chromatograph the analytes. A flow of 50 microliters/min of
      the column effluent was diverted to the ESI source. The effects of acid
      concentration on ESI-MS detector response in the mobile phase were investigated.
      The effects on the production of diagnostic fragments produced by varying the
      orifice plate voltage and the response of the MS detector were also evaluated.
      For the analyte considered, the response of the mass detector was linearly
      related to the amount of analyte injected between 1 and 50 ng. The limit of
      detection (signal-to-noise ratio = 3) of the method for the pesticides considered
      in drinking water samples was estimated to be about 2-5 ng/l.

PMID- 9561759
TI  - Comparison of the protein adsorption selectivity of salt-promoted agarose-based
      adsorbents. Hydrophobic, thiophilic and electron donor-acceptor adsorbents.
AB  - Protein adsorption of human serum onto six different agarose-based
      chromatographic gels that were representative of the salt-promoted adsorbent
      family [octyl- and phenyl-Sepharose, mercaptoethanol-divinyl sulfone agarose (T
      gel), mercaptomethylene pyridine-derivatized agarose gel (MP gel),
      tricyanoaminopropene-divinyl sulfone agarose (DVS-TCP gel), tricyanoamino-propene
      bisoxirane agarose (bisoxirane-TCP gel)] was studied in the presence of moderate
      or high concentrations of the water structuring salt, sodium sulfate. Study of
      the protein adsorption selectivity by two-dimensional gel electrophoresis
      revealed an opposed selectivity for hydrophobic interaction adsorbents and
      electron donor-acceptor adsorbents. The T gel, MP gel and TCP gels belonged to
      the electron donor-acceptor adsorbents, displaying a main selectivity for
      immunoglobulins, whereas octyl-Sepharose belonged to the hydrophobic adsorbents,
      displaying a main selectivity for 'hydrophobic' proteins. Phenyl-Sepharose for
      its part was described as an example of a composite selectivity of both families.
      The conclusion of this work is two-fold: (1) hydrophobic interaction
      chromatography (HIC) and electron donor-acceptor chromatography (EDAC) have
      opposed protein selectivities and are both salt-promoted. As a main consequence,
      it means that high concentrations of a water-structuring salt can promote
      different types of weak molecular interactions, resulting in different protein
      adsorption selectivities: (2) thiophilic adsorption chromatography (TAC) should
      be renamed EDAC as similar protein selectivity is demonstrated for electron donor
      acceptor ligand devoid of sulfur atoms.

PMID- 9561760
TI  - Evaluation of the immobilized artificial membrane phosphatidylcholine. Drug
      discovery column for high-performance liquid chromatographic screening of drug
      membrane interactions.
AB  - Chromatographic retention factors (k') of a series of eight beta-adrenoceptor
      antagonist compounds (beta-adrenolytic drugs) were determined employing an
      immobilized artificial membrane column (IAM.PC.DD). The influence of mobile phase
      pH, ionic strength, and organic modifier composition was studied in order to
      examine column performance. After the IAM.PC.DD columns were exposed to
      approximately 7000 column volumes of a 0.01 M PBS mobile phase, five out of six
      columns tested showed significant peak broadening and decreased k' values
      indicative of premature column failure. The data suggested that the immobilized
      phospholipids stationary phase was removed by the 0.01 M PBS mobile phase. The
      beta-adrenolytic drug's log k'IAM values obtained with an IAM.PC.DD column were
      compared to an esterIAM.PC.MG column for predicting drug membrane interactions.
      For the linear regression analysis between log k'IAM and the logarithm of the n
      octanol-water partition coefficients (rIAM.PC.DD = 0.8710 vs. rIAM.PC.MG =
      0.9538), the C18 HPLC retention factors (rIAM.PC.DD = 0.8408 vs. rIAM.PC.MG =
      0.9380), the liposome partition coefficients (rIAM.PC.DD = 0.8887 vs. rIAM.PC.MG
      = 0.9187), and various pharmacokinetic parameters, significantly better
      correlations were obtained with the esterIAM.PC.MG column than the IAM.PC.DD
      column.

PMID- 9561761
TI  - Simultaneous separation of flavanone glycosides and polymethoxylated flavones in
      citrus juices using liquid chromatography.
AB  - We present a simultaneous liquid chromatographic method for the separation of two
      flavonoid compound families, flavanone glycosides (FGs) and polymethoxylated
      flavones (PMFs), which are usually found in citrus fruits species and varieties.
      This technique permits the quantitation of six FGs (narirutin, naringin,
      hesperidin, neohesperidin, didymin, poncirin) and six PMFs (sinensetin,
      hexamethoxyflavone, nobiletin, scutellarein, heptamethoxyflavone and tangeretin).
      This technique, to be used to characterize a citrus juice by its polyphenolic
      profile, has been applied to the determination of flavonoid compounds in
      grapefruit- and orange juice. Differentiation of orange juice varieties and
      mixtures containing tangor juice using polyphenolic profiles and flavonoid
      content has been achieved.

PMID- 9561762
TI  - Introduction of a new scale into reversed-phase high-performance liquid
      chromatography of pyridylamino sugar chains for structural assignment.
AB  - Addition of a monosaccharide residue to a pyridylaminated (PA)-N-linked sugar
      chain results in an increment or decrement in the elution time on reversed-phase
      HPLC, the difference being defined as the partial elution time of the residue.
      Based on this principle, an empirical rule was deduced, which states that the
      elution time is roughly equal to the sum of the partial elution times of the
      component sugar residues [Anal. Biochem., 167 (1987) 321-326]. In practice,
      however, some partial elution times obtained from different pairs of mother PA
      sugar chains are found to deviate, and consequently the closeness of the elution
      times of PA-sugar chains calculated therefrom to the observed times is reduced in
      such cases. To improve the reliability of the additivity rule and to generalize
      elution times so that they are less dependent on minor alterations in the elution
      conditions, we have devised a new scale for elution time, which we have named a
      reversed-phase scale. The elution times on the reversed-phase scale (the R
      values) are read from a conversion curve constructed using the elution times of
      eight selected standard PA-sugar chains. The partial elution times on the
      reversed-phase scale of 22 monosaccharide residues were calculated from the R
      values of 93 PA-sugar chains. The R values obtained by summing the partial
      elution times of all the component monosaccharide residues became much closer to
      the R values obtained from the reversed-phase scale, compared to the results
      obtained using the previous method. In addition, the R values were less
      influenced by minor change in the elution conditions. These features of the new
      scale allow more accurate structural assignment of sugar chains.

PMID- 9561763
TI  - Chromatographic purification of human alpha 1 proteinase inhibitor from dissolved
      Cohn fraction IV-1 paste.
AB  - A novel chromatographic process for purification of alpha 1 proteinase inhibitor
      (alpha 1-PI) from Cohn fraction IV-1 paste is described. This process has been
      successfully scaled up to 50-1 columns. It involves DEAE chromatography,
      sulfopropyl (S) cation chromatography, tri-n-butyl phosphate (TNBP)-cholate
      treatment, a second S cation chromatography, freeze-drying and dry-heat. The
      process has been optimized for purity, yield, lipid removal, chemical usage and
      water consumption. Filtration after TNBP-cholate treatment plays a key role in
      ensuring a low lipid content in the final product. Pre-equilibration with high
      salt buffer is necessary to reduce the water consumption significantly during the
      ion-exchange chromatography equilibration step. The final product is
      approximately 95% pure by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, with a 64% to 70% yield from IV-1 paste.

PMID- 9561764
TI  - High sample throughput flow immunoassay utilising restricted access columns for
      the separation of bound and free label.
AB  - A flow immunodetection system with high sample throughput capacity is described
      for the screening of various analytes. The immunochemical detection principle is
      based on the chromatographic separation of the formed immunocomplex (AbAg or
      AbAg*) and the free antigen (Ag) by a restricted access (RA) column, utilising
      size-exclusion and reversed-phase mechanism. A fluorescein labelled analyte (Ag*)
      was used in the competitive assay format with fluorescence detection. The speed
      and simplicity of the assay were the greatest advantages, allowing measurement of
      the analyte to be carried out in less than 1 min. The biocompatibility and
      capacity of the restricted access material allowed multiple injections of up to
      5000, without any breakthrough of the fluorescent tracer molecule and thus need
      for regeneration. The flow immunoassay was developed using the well-known
      atrazine herbicide and some transformation products as model compounds, due to
      their human toxicity and widespread use. The sample throughput was 80 samples per
      hour and the detection limits were 1.4 nM (300 pg/ml) for atrazine (Ab I) and 2.3
      nM (500 pg/ml) for the sum of triazines (Ab II-III). Different sample matrices,
      PBS buffer, creek water, and urine were successfully applied in the flow system
      without the need for any sample handling step. For plasma samples an additional
      clean-up step using solid-phase extraction had to be included. The resulting
      detection limits for atrazine in plasma and water samples using this clean-up and
      trace enrichment procedure were found to be 2 ng/ml and 20 pg/ml, respectively.
      The analysis could be performed at a sample throughput rate of 400 per 6-h
      working shift.

PMID- 9561765
TI  - On-line pretreatment and determination of Pb, Cu and Cd at the microgram l-1
      level in drinking water by chelation ion chromatography.
AB  - A novel, highly sensitive method for the simultaneous separation and
      determination of lead, copper, cadmium and other transition metals in drinking
      water was achieved by on-line sample pretreatment of chelation ion
      chromatography. Manganese, which coeluted with cadmium, was oxidized to
      permanganate by ammonium persulfate before injection. Permanganate, with bulk
      quantity of alkali, alkaline earth metals, iron and aluminum, was eliminated by
      pyrophosphoric acid-ammonium acetate buffer solution (pH 5.5), while retaining
      heavy and transition metals on a selective chelating resin (MetPac CC-1 column).
      Then, they were disabsorbed and transferred to a sulfonated cation exchanger (TMC
      1 column). Finally, the concentrated trace metals were separated on a
      bifunctional ion-exchange column (CS5A) by a concentration gradient of oxalic
      acid and sodium nitrate eluents, coupled with post-column spectrophotometric
      detection with 2-[(5-bromo-2-pyridyl)azo]-5-diethylaminophenol (5-Br-PADAP) at
      560 nm. The separation and color-development conditions were optimized. The
      detection limits for the method (signal-to-noise ratio = 3:1) were at or below
      the microgram l-1 level. The results of drinking water analyses were
      satisfactory.

PMID- 9561766
TI  - Solid-phase microextraction of polychlorinated biphenyls.
AB  - The extraction and analysis of 21 polychlorinated biphenyls (PCBs) ranging from
      di- to decachlorobiphenyls in ocean, wetland and leachate water samples were
      achieved using solid-phase microextraction (SPME) with a 100-micron poly(di
      methylsiloxane) (PDMS) fiber and gas chromatography-electron-capture detection
      (GC-ECD). Severe carryover between samples (e.g., 20%) occurs on both stir bars
      and the SPME fibers demonstrating that it is important to use a new stir bar for
      each sample, as well as to perform SPME-GC blanks between samples to avoid
      quantitative errors. The equilibrium partitioning coefficients of individual PCB
      congeners between PDMS and water were found to be surprisingly different compared
      to their octanol-water partitioning coefficient (Kow), demonstrating that Kow
      cannot be used to estimate the partitioning behavior of PCBs in the SPME process.
      Using a 15-min SPME extraction, SPME analysis with GC-ECD was linear (r2 > or =
      0.97) from approximately 5 pg/ml to the solubility limit of each congener.
      Concentrations in water samples obtained by 15-min SPME extractions compared
      favorably with those obtained by toluene extractions, demonstrating that SPME
      combined with GC is a useful technique for the rapid determination of PCBs in
      water samples.

PMID- 9561767
TI  - Trace analysis of tributyltin and triphenyltin compounds in sea water by gas
      chromatography-negative ion chemical ionization mass spectrometry.
AB  - An analytical gas chromatography-mass spectrometry (GC-MS) method using negative
      ion chemical ionization (NICI) has been investigated for the determination of
      trace tributyltin (TBT) and triphenyltin (TPhT) compounds in sea water. TBT and
      TPhT were extracted from samples as chloride under the acidic condition of HCl.
      Doping of the GC system with a dilute HBr-methanolic solution resulted in direct
      detection of the chlorides of TBT, TPhT and tripentyltin (TPenT, internal
      standard). As the result of HBr doping, a sharp peak of the respective organotin
      bromides appeared: during GC analysis, halogen exchange from the chloride to the
      bromide occurred. NICI-MS was highly selective and sensitive for the detection of
      TBT. TPhT and TPenT bromides. In the selected ion monitoring mode of NICI-MS, the
      minimum detectable amounts defined as the signal equal to three times the
      standard deviation (3 sigma) of the baseline noise were 20 and 25 pg ml-1 for TBT
      and TPhT, respectively. These amounts are approximately 250-400 times better than
      those in electron impact mode. The combination of GC using an apolar capillary
      column doped with a dilute HBr-methanolic solution and NICI-MS made it possible
      to determine TBT and TPhT at less than the ng l-1 level in sea water.

PMID- 9561768
TI  - Separation of amino acid and peptide stereoisomers by nonionic micelle-mediated
      capillary electrophoresis after chiral derivatization.
AB  - Enantiomers of amino acids and peptides were derivatized with a fluorescent
      chiral reagent, 4-(3-isothiocyanatopyrrolidinl-yl)-7-nitro-2,1,3-benzoxadiazole
      [R-(-)- or S-(+)-NBD-PyNCS] and the resulting diastereomeric derivatives
      separated by capillary electrophoresis (CE). The CE running buffer consisted of
      25 mM acetate buffer (pH 4) and 10 mM of the nonionic surfactant Triton X-100.
      The excitation maximum of NBD-PyNCS at 480 nm matches the major Ar-ion emission
      line at 488 nm allowing sensitive laser-induced fluorescence detection with
      limits of detection around 50 nM. D-Proline and D-aspartate spiked (at 10(-4) M
      and 10(-5) M concentrations, respectively) into complex biological matrices
      (rabbit serum and homogenate of Aplysia californica buccal ganglion) are detected
      without matrix interferences. This method has also been applied to the
      determination of D- and L-amino acid residues in peptides after acid hydrolysis.
      Results from the chiral analysis of the naturally-occurring peptide, gramicidin
      D, are shown.

PMID- 9561769
TI  - Validation of a capillary isoelectric focusing method for the recombinant
      monoclonal antibody C2B8.
AB  - A capillary isoelectric focusing (cIEF) method has been developed for the purpose
      of determining the identity and charge distribution of mouse/human chimeric
      antibody to human CD20 antigen (C2B8). The assay was validated in accordance with
      ICH guidelines in order to demonstrate that it is suitable for its intended
      purpose and so that it may be performed as a lot release test for bulk and final
      product. As a result of the validation process the assay was found to be linear
      over the concentration range of 2-356 micrograms ml-1 with recovery of 125I
      labeled C2B8 at the target sample concentration of 125 micrograms ml-1 equal to
      99%. The repeatability and intermediate precision relative standard deviations of
      the four major peaks for migration time, peak area, and peak area percent ranged
      from 0.9-4.4%. The specificity of the assay was demonstrated by baseline
      resolution of the C2B8 main peak from product excipients, and other Genentech
      monoclonal antibodies. The results of this validation demonstrate that the cIEF
      assay for the determination of identity and charge distribution of C2B8 is
      accurate, precise, linear, and highly specific. The assay is rapid and suitably
      rugged.

PMID- 9561770
TI  - Novel quartz flow-cell as a post-column photochemical reactor for high
      performance liquid chromatography.
AB  - The construction of a new post-column photochemical reactor with quartz flow
      cells in series for high-performance liquid chromatography (HPLC) is described.
      The performance of the new reactor was compared with a conventional open tubular
      PTFE coil reactor. The sensitivity, accuracy and precision obtained with both
      reactors are comparable. The new reactor has the obvious advantages of smaller
      cell volume as well as inertness and resistance to not only light and heat
      produced by the UV lamp, but also to organic solvents in the mobile phases, which
      results in greatly improved durability, reduced peak broadening and shorter
      chromatographic run times. Application of the new reactor to the fluorescence
      detection of DU-6859a, a new fluoroquinolone antimicrobial agent, in human serum
      is reported.

PMID- 9561771
TI  - Host cell and malarial targets for docetaxel (Taxotere) during the erythrocytic
      development of Plasmodium falciparum.
AB  - The microtubular stabilizing agent docetaxel (Taxotere) is known to inhibit the
      intraerythrocytic development of Plasmodium falciparum. To investigate the
      mechanism(s) of inhibition, we analyzed the structural organization of the
      mitotic spindle by immunofluorescence and electron microscopy. When 30 microM
      docetaxel was applied for five hours on ring forms, alterations in the mitotic
      spindles leading to abnormal nuclear divisions were observed. At the trophozoite-
      and schizont-stage, docetaxel pulses prevent mitosis by stabilizing microtubular
      structures associated with the mitotic apparatus, giving abnormal spindles.
      However, this inhibition did not interfere with parasite DNA synthesis indicating
      the absence of a checkpoint that couples exit from mitosis with proper spindle
      assembly as observed in higher eukaryotic cells. In parallel, intraerythrocytic
      concentration of docetaxel was measured in parasitized erythrocytes, after
      incubation of cells with 3H-docetaxel for five hours. It was found to be 14-fold
      increased at the ring-stage of infected erythrocytes compared to normal ones, 170
      fold increased at the trophozoite-stage and 1,500-fold increased at the schizont
      stage. Our data show that, even though the overall intracellular concentration of
      docetaxel is low in docetaxel-pulsed rings, the agent might be sufficient to
      disturb the spindle organization. However, the existence of targets for docetaxel
      other than mitotic spindle microtubules, i.e. erythrocyte membrane components
      could interfere with mitotic spindle formation.

PMID- 9561773
TI  - A developmentally eliminated sequence in the flanking region of the histone H1
      gene in Tetrahymena thermophila contains short repeats.
AB  - In Tetrahymena, as in other ciliated protozoans, a transcriptionally active,
      'somatic' macronucleus develops from a transcriptionally inactive 'germline'
      micronucleus after conjugation. The process of development involves elimination
      of germline DNA segments at thousands of locations in the genome. The
      characterization of one of these segments in Tetrahymena thermophila is described
      here. This micronucleus-specific DNA has been identified by comparing the
      sequence of the corresponding micronuclear and macronuclear regions. The
      micronucleus-specific DNA is over 1 kb long, is AT-rich and has TTT direct
      repeats at its termini. At one end of the micronuclear sequence there is a 130 bp
      duplication, and at the other end there are several related repeats of a 13-mer.
      Short G-rich sections are found in the middle of the eliminated DNA, as well as
      on one side of the rearrangement junction. Short G-rich segments are also
      detectable in three previously described micronucleus-specific sequences. The
      micronuclear sequence described here is a member of a repeat family. Cross
      hybridizing sequences are also detectable in some other Tetrahymena species. The
      distribution of cross-hybridizing sequences among related species is not
      consistent with the phylogenetic tree.

PMID- 9561772
TI  - Phylogenetic analysis of coccidia based on 18S rDNA sequence comparison indicates
      that Isospora is most closely related to Toxoplasma and Neospora.
AB  - The phylogenetic relationships and taxonomic affinities of coccidia with
      isosporan-type oocysts have been unclear as overlapping characters, recently
      discovered life cycle features, and even recently discovered taxa, continue to be
      incorporated into biological classifications of the group. We determined the full
      or partial 18S ribosomal RNA gene sequences of three mammalian Isospora spp.,
      Isospora felis, Isospora ohioensis and Isospora suis, and a Sarcocystis sp. of a
      rattlesnake, and used these sequences for a phylogenetic analysis of the genus
      Isospora and the cyst-forming coccidia. Various alveolate 18S rDNA sequences were
      aligned and analyzed using maximum parsimony to obtain a phylogenetic hypothesis
      for the group. The three Isospora spp. were found to be most closely related to
      Toxoplasma gondii and Neospora caninum. This clade in turn formed the sister
      group to the Sarcocystis spp. included in the analysis. The results confirm that
      the genus Isospora does not belong to the family Eimeriidae, but should be
      classified together with the cyst-forming coccidia in the family Sarcocystidae.
      Furthermore, there appear to be two lineages within the Sarcocystidae. One
      lineage comprises Isospora and the Toxoplasma/Neospora clade which share the
      characters of having a proliferative phase of development preceding gamogony in
      the definitive host and an exogenous phase of sporogony. The other lineage
      comprises the Sarcocystis spp. which have no proliferative phase in the
      definitive host and an endogenous phase of sporogony.

PMID- 9561774
TI  - The striated bands of Paramecium are immunologically distinct from the centrin
      specific infraciliary lattice and cytostomal cord.
AB  - The pellicle of Paramecium has three two-dimensionally arrayed systems that
      occupy separate but closely paralleling planes. All three systems are now
      distinguishable by their differing immunological properties. This study focused
      on the two deeper systems. The infraciliary lattice lies innermost and labels
      with centrin-specific antibodies. The middle system, the striated bands, is
      specifically labeled with a monoclonal antibody that we have raised to a 110 kDa
      cortical antigen in P. multimicronucleatum. This antibody labels a similar
      geometric cortical pattern in at least two species, P. multimicronucleatum and P.
      tetraurelia. Centrin-specific structures appear to be net-like in the above two
      species but show a more interrupted pattern in P. caudatum. The cytostomal cord
      is an essentially unbranched extension of the net-like infraciliary lattice and,
      like it, is centrin-specific. The cord has a unique association with the alveolar
      sacs which suggest these calcium-storing compartments contribute to the calcium
      fluxes required for contraction of the cord. A structural rather than a
      contractile function is favored for the striated bands, based solely on their
      morphology.

PMID- 9561775
TI  - Immunocytochemical identification of spore proteins in two microsporidia, with
      emphasis on extrusion apparatus.
AB  - Microsporidia can form small spores with a unique invasive apparatus featuring a
      long polar tube whose extrusion allows entry of infectious sporoplasm into a host
      cell. The reactivity of mouse polyclonal antibodies raised against sporal
      proteins from two microsporidian species belonging to different genera (Glugea
      atherinae and Encephalitozoon cuniculi) was studied by western blotting and
      indirect immunofluorescence. Whole protein antisera provided a few cross
      reactions relatable to some proteins of the spore envelope or polar tube.
      Ultrastructural immunocytochemistry with murine antibodies against protein bands
      separated by sodium dodecylsulphate polyacrylamide gel electrophoresis allowed
      the assignment of several proteins to the polar tube (34, 75 and 170 kDa in
      Glugea, 35, 55 and 150 kDa in Encephalitozoon). Antigenic similarities were
      detected for the Glugea 34 kDa and Encephalitozoon 35 kDa polar tube proteins.
      Species-specific proteins were shown to be located in either the lamellar
      polaroplast of Glugea or the spore envelope of Encephalitozoon.

PMID- 9561776
TI  - Entamoeba dispar: cultivation with sterilized Crithidia fasciculata.
AB  - Four isolates of Entamoeba dispar identified by their hexokinase and
      phosphoglucomutase isoenzyme profile and by their failure to react with Entamoeba
      histolytica-specific monoclonal antibody (4G6) could be grown in either Diamond's
      BI-S-33 medium, newly developed BCSI-S (Biosate cysteine starch iron-serum)
      medium, or casein-free YI-S medium in the presence of Crithidia fasciculata (ReF
      1:PRR) sterilized by heating 56 degrees C for 30 min and subsequent incubation
      with 1% hydrogen peroxide for 24 hours at 4 degrees C. After the cultures were
      maintained for over 50 passages, the amebae were identified as E. dispar by
      isoenzyme analysis, polymerase chain reaction with E. histolytica- and E. dispar
      specific primers, i.e. p11 plus p12 and p13 plus p14, respectively, and by
      negative reactivity with monoclonal antibody 4G6. The flagellates added to the
      culture were judged to be metabolically inactive based on the results of nuclear
      magnetic resonance spectroscopy, electron microscopy, and polarographic analysis.
      All of these findings suggest that E. dispar can grow in vitro with metabolically
      inactive C. fasciculata as a culture associate.

PMID- 9561777
TI  - Identification of significant variation in the composition of lipophosphoglycan
      like molecules of E. histolytica and E. dispar.
AB  - The lipophosphoglycan-like (LPG-like) molecules of E. histolytica virulent
      strains are clearly distinct from those of the avirulent E. histolytica and E.
      dispar strains. Abundant 'LPG' levels are apparently limited to virulent strains,
      while lipophosphopeptidoglycans ('LPPG's) are common to both virulent and
      avirulent strains of E. histolytica and E. dispar. It is therefore conceivable
      that 'LPPG' performs a function that is essential to survival within the host,
      while the 'LPG' performs a more specific function related to virulence.

PMID- 9561778
TI  - Molecular analysis of the Gal/GalNAc adhesin of Entamoeba histolytica.
AB  - Attachment of Entamoeba histolytica to colonic epithelium and a variety of other
      target cells is mediated by a galactose/N-acetyl D-galactosamine (Gal/GalNAc)
      inhibitable adhesin. Seven monoclonal antibodies specific for nonoverlapping
      epitopes of the 170 kDa subunit have been shown to have distinct effects on
      adherence. Four of these monoclonal antibodies inhibit or have no effect on
      amebic adherence while two others enhance amebic adherence. The epitopes
      recognized by these seven monoclonal antibodies have been mapped to the
      extracellular cysteine rich region of the 170 kDa subunit. The conformational
      nature of the epitopes was examined by testing monoclonal antibody reactivity
      with isolated regions of the 170 kDa subunit expressed as fusion proteins in E.
      coli and also with denatured native adhesin. These analyses suggested that three
      of monoclonal antibodies recognized conformational epitopes while the remaining
      four recognized linear epitopes. The mapping of these monoclonal antibodies have
      identified functionally important regions of the Gal/GalNAc adhesin and have also
      shown that recombinant Gal/GalNAc adhesin, when expressed in E.coli, retained at
      least some of its native conformation.

PMID- 9561779
TI  - Functional heterogeneity of colonic adenocarcinoma mucins for inhibition of
      Entamoeba histolytica adherence to target cells.
AB  - Mucins secreted from the gastrointestinal epithelium from the basis of the
      adherent mucus layer which is the host's first line of defense against invasion
      by Entamoeba histolytica. Galactose and N-acetyl-D-galactosamine residues of
      mucins specifically inhibit binding of the amebic 170 kDa heavy subunit Gal
      lectin to target cells, an absolute prerequisite for pathogenesis. Herein we
      characterized the secretory mucins isolated from the human colon and from three
      human colonic adenocarcinoma cell lines: two with goblet cell-like (LS174T and
      T84) and one with absorptive cell-like morphology (Caco-2). By Northern blot
      analysis the intestinal mucin genes MUC2 and MUC3 were constitutively expressed
      by confluent LS174T and Caco-2 cells, whereas T84 cells only transcribed MUC2 and
      not MUC3 mRNA. 3H-glucosamine and 3H-threonine metabolically labeled proteins
      separated as high M, mucins in the void (Vo > 10(6) Da) of Sepharose-4B column
      chromatography and remained in the stacking gel of SDS-PAGE as depicted by
      fluorography. All mucin preparations contained high amounts of N-acetyl
      glucosamine, galactose, N-acetyl-galactosamine, fucose and sialic acid,
      saccharides typical of the O-linked carbohydrate side chains. Mucin samples from
      the human colon and from LS174T and Caco-2 cells inhibited E. histolytica
      adherence to chinese hamster ovary cells, whereas mucins from T84 cells did not.
      These results suggest that genetic heterogeneity and/or posttranslational
      modification in glycosylation of colonic mucins can affect specific epithelial
      barrier function against intestinal pathogens.

PMID- 9561780
TI  - The effects of Entamoeba histolytica lysates on human colonic mucins.
AB  - Detergent lysates of Entamoeba histolytica trophozoites contained high levels of
      beta-N acetyl-D-glucosaminidase, beta-N acetyl-D-galactosaminidase and alpha-D
      galactosidase activity, and lower but significant levels of five other
      glycosidases. Although these activities should have been capable of largely
      degrading the oligosaccharide side-chains of human colonic mucin, in fact only
      about one third of high MW mucin was degraded in 72 h and trypsin alone produced
      a similar effect. There was no evidence that these glycosidases were excreted and
      we conclude that they are unlikely to represent significant virulence factors for
      E. histolytica.

PMID- 9561781
TI  - Molecular changes in Entamoeba histolytica in response to bacteria.
AB  - Entamoeba histolytica, the protozoan parasite, is the causative agent of
      amoebiasis. The degree of virulence, as inferred from invasiveness, of
      potentially pathogenic strains may be regulated by both host and parasite factors
      that determine the gut environment. One such factor that plays an important role
      is the bacterial flora in the gut. Previous studies have clearly shown that
      bacterial flora is an important determinant of virulence in E. histolytica.
      However, the exact nature of changes induced in E. histolytica in response to
      bacteria and their role in virulence is not clear. In this study the levels of a
      number of molecules potentially important in virulence mechanisms were determined
      in E. histolytica cells grown with and without normal human bacterial flora,
      using enzyme-linked immunosorbent assay. Significant changes were observed only
      after the E. histolytica cells had been adapted to grow with bacterial flora for
      a number of generations, and not in short term culture.

PMID- 9561782
TI  - When theories of speech meet the real world.
AB  - Two theories of speech--one quite conventional, the other much less so--account
      very differently for the biological advantage of speech over writing/reading. The
      guiding assumption of the more conventional theory is that the elements of speech
      are sounds, and that these are served by processes of motor control and auditory
      perception that are in no way specialized for language. Accordingly, there must
      be a cognitive stage, beyond action and perception, where the motor and auditory
      representations are somehow invested with linguistic significance. On the
      conventional view, then, the sounds of speech are just like the letters of the
      alphabet. Neither has more than an arbitrary relation to language, hence the
      difference between them is trivially a matter of which of the equally large gaps
      between signal and message needs to be bridged. On the less conventional theory,
      the ultimate constituents of speech are not sounds, but articulatory gestures.
      Having evolved exclusively in the service of language, they form a natural class,
      a phonetic modality. Being phonetic to begin with, they do not require to be made
      so by cognitive translation. And that, very simply, is the advantage of speech
      over writing/reading. Speech has the corollary advantage that it is managed by a
      module biologically adapted to circumvent limitations of tongue and ear by
      automatically coarticulating the constituent gestures and coping with the complex
      acoustic consequences. But a result is that awareness of phonetic structure is
      not normally a product of having learned to speak: The module "spells"--that is,
      sequences phonetic segments--for the speaker and recovers the segments for the
      listener, leaving both in the dark about the way that is done; the gestural
      representations are immediately phonetic in nature, precluding the cognitive
      translation that would bring them to notice; and coarticulation destroys all
      correspondence in segmentation between acoustic and phonetic structures, making
      it that much harder to demonstrate the alphabetic nature of speech at the
      acoustic surface. Accordingly, special difficulty in becoming literate might be
      caused by a weakness of the phonetic module, for that would produce primary
      representations of a fragile sort, with the consequence that they would be that
      much harder to bring to awareness--as is required if they are to serve writers
      and readers as the units of an alphabetic script--and also that much less able to
      bear the weight of working memory.

PMID- 9561783
TI  - The changing relationship between anatomic and cognitive explanation in the
      neuropsychology of language.
AB  - Changing trends in the approach to neurolinguistics are reviewed. We suggest that
      these trends are marked by a distinct convergence between linguistic/cognitive
      and anatomic/physiological approaches to the study of aphasia. With respect to
      the former, we cite the refinement of analysis of language symptoms and the
      introduction of experimental methods that reveal real-time aspects of language
      processing. With respect to the latter, we cite the technical advances in static
      and dynamic brain imaging that have allowed the in vivo analysis of lesion sites
      in aphasic patients, and the identification of foci of metabolic activity during
      linguistic/cognitive tasks in normal brains. We cite recent imaging studies of
      category-specific lexical dissociations as examples of the productive convergence
      of anatomic and technological advances to illuminate a particularly challenging
      problem.

PMID- 9561784
TI  - The neurological organization of some aspects of sentence comprehension.
AB  - I briefly review 25 years of aphasia research directed to uncovering the
      neurological organization of sentence comprehension capacity. I provide a
      description of aphasic comprehension disorders offered along syntactic lines, and
      I connect the syntactic limitation (revealed in this description) to the
      disruption of cortically localizable processing resources.

PMID- 9561790
TI  - Comparative analysis of microsatellite and allozyme markers: a case study
      investigating microgeographic differentiation in brown trout (Salmo trutta).
AB  - A comparative study between microsatellite and allozyme markers was conducted on
      natural populations of resident brown trout (Salmo trutta) sampled over a reduced
      geographical scale and on hatchery strains. The higher level of polymorphism
      observed at microsatellite loci resulted in higher power of statistical tests for
      differentiation among population samples and for genotypic linkage
      disequilibrium. Genetic distances of Cavalli-Sforza and Edwards were on average
      two times larger for microsatellites than for allozymes but multilocus FST
      estimates computed over the entire set of populations were not significantly
      different for both categories of markers. Assignment tests of individual fish to
      the set of sampled populations demonstrated a much higher efficiency of
      microsatellites compared to allozymes. Pairwise multilocus FST estimates were
      significantly correlated to waterway distances and there was a significant
      tendency for the incorrectly classified individuals to be assigned to one of the
      nearest populations, indicating that isolation-by-distance acted significantly on
      brown trout populations. This increase of differentiation with distance was
      higher for allozymes than for microsatellites. Traditional measures of genetic
      differentiation (Cavalli-Sforza and Edwards' chord distance and FST) were
      compared for microsatellites to recently proposed statistics taking into account
      allele size differences (Goldstein's distance and PST). Using Goldstein's
      distance for neighbour-joining analysis did not improve the tree structure
      resolution. Multilocus estimates of PST and FST were not significantly different
      when computed over the entire set of populations but no significant correlation
      was detected between matrices of pairwise multilocus PST estimates and waterway
      distances.

PMID- 9561792
TI  - Identification of microsatellite markers in the snow crab Chionoecetes opilio.

PMID- 9561785
TI  - The pros and cons of masked priming.
AB  - Masked priming paradigms offer the promise of tapping automatic, strategy-free
      lexical processing, as evidenced by the lack of expectancy disconfirmation
      effects, and proportionality effects in semantic priming experiments. But several
      recent findings suggest the effects may be prelexical. These findings concern
      nonword priming effects in lexical decision and naming, the effects of mixed-case
      presentation on nonword priming, and the dependence of priming on the nature of
      the distractors in lexical decision, suggesting possible strategy effects. The
      theory underlying each of these effects is discussed, and alternative
      explanations are developed that do not preclude a lexical basis for masked
      priming effects.

PMID- 9561793
TI  - Development of primers for polymorphic microsatellite loci in the Pacific herring
      (Clupea harengus pallasi).

PMID- 9561794
TI  - Isolation and characterization of microsatellite markers in the Ixodes ricinus
      complex (Acari: Ixodidae).

PMID- 9561796
TI  - Evaluation of charging on macromolecules in electron cryomicroscopy.
AB  - We describe procedures to assess charging of biological specimens under electron
      irradiation in an electron cryomicroscope. Charging can be observed by an
      expansion of the illuminating beam, blurring of electron diffraction patterns and
      by beam "footprints" on the specimen. Discharging can also be seen in the
      defocused electron diffraction mode. We investigated the influence of a variety
      of factors on the magnitude and visibility of charging. A reduction of charging
      is noticed when part of the adjacent carbon film is included in the irradiated
      specimen area.

PMID- 9561797
TI  - 3D reconstruction in electron microscopy using ART with smooth spherically
      symmetric volume elements (blobs).
AB  - Algebraic reconstruction techniques (ART) are iterative procedures for solving
      systems of linear equations. They have been used in tomography to recover objects
      from their projections. In this work we apply an ART approach in which the basis
      functions used to describe the objects are not based on voxels, but are much
      smoother functions named "blobs". The data collection studied in this work
      follows the so-called "conical tilt geometry" that is commonly used in many
      applications of three-dimensional electron microscopy of biological
      macromolecules. The performance of ART with blobs is carefully compared with a
      currently well-known three dimensional (3D) reconstruction algorithm (weighted
      back projection) using a methodology which assigns a level of statistical
      significance to a claim of relative superiority of one algorithm over another for
      a particular task. The conclusion we reach is that ART with blobs produces high
      quality reconstructions and is, in particular, superior to weighted
      backprojection in recovering features along the "vertical" direction. For the
      exact implementation recommended in this paper, the computational costs of ART
      are almost an order of magnitude smaller than those of WBP.

PMID- 9561798
TI  - In adrenocortical tissue, annexins II and VI are attached to clathrin coated
      vesicles in a calcium-independent manner.
AB  - We have previously characterized three populations of clathrin coated vesicles
      (CCVs) isolated from bovine adrenocortical tissue and designated them as large,
      medium and small coated vesicles, i.e., LCV, MCV and SCV, respectively. Here, we
      show that annexins II and VI, two of the annexins involved in membrane traffic,
      are present in the three populations of CCVs but with different distributions
      between coat proteins (CP) and lipidic vesicle membrane. Annexin VI is only
      associated with the membrane, whatever the CCV population. In contrast, annexin
      II is differently distributed between coat and membrane, depending on the CCV
      population. Both annexins are bound to membranes in a calcium-independent manner
      and solubilization studies in Triton X114 (TX114) suggest that they interact
      poorly with lipids by hydrophobic interactions. Ligand blotting experiments show
      that both annexins bind to CCV proteins: annexin II to a 200-kDa component in all
      CCVs and annexin VI to a 100-kDa component in LCV and SCV identified as dynamin,
      a GTPase essential for endocytic CCV pinching off. Dynamin is tightly associated
      to annexin VI only in LCVs, the endocytic [transferrin (Tf) positive] vesicles.
      Our data suggest that annexins II and VI could define specific protein-lipid
      interaction microdomains that could play a role in the different functions of the
      CCVs.

PMID- 9561799
TI  - Alpha 1-proteinase inhibitor is the serum regulator of the activity of p57, a C3
      cleaving proteinase present in human erythrocyte membranes.
AB  - Human erythrocytes express at the membrane level a p57 serine proteinase which
      cleaves C3, the third component of complement. We demonstrated herein that human
      serum carries an inhibitory activity against this p57 membrane proteinase.
      Purification allowed to identify this inhibitor as the alpha 1-proteinase
      inhibitor (alpha 1-PI) on the basis of its molecular weight, antigenicity and
      amino acid sequence identity. Data demonstrated that alpha 1-PI is the unique and
      strong serum inhibitor of the p57 proteinase activity: inhibition studies showed
      that alpha 1-PI inhibited p57 proteinase activity with a kass value of 10(5) M-1
      s-1. Inhibition of p57 proteinase by alpha 1-PI was due to formation of a SDS
      stable complex between both components. We suggest that inhibition of the
      membrane p57 proteinase activity by serum alpha 1-PI may be involved in the
      regulation of C3 fragment generation and/or in clearance in liver of C3b bearing
      immune complexes by erythrocyte-CR1.

PMID- 9561800
TI  - Lack of 2',5'-oligoadenylate-dependent RNase expression in the human hepatoma
      cell line HepG2.
AB  - 2',5'-adenylate oligonucleotide (2-5A)-dependent RNase and 2-5A-synthetase are
      two enzymes of the 2-5A system strongly implicated in the basal control of RNA
      decay of both interferon-treated and untreated cells. RNase is activated by a 2
      5A produced by 2-5A-synthetase, both enzymes being overexpressed by type I
      interferon (alpha/beta). We described here for the first time a cell line
      completely deficient in RNase and its mRNA, while p69 2-5A-synthetase was
      normally interferon alpha/beta-induced. The complete absence of this RNase in
      human hepatoma cells (HepG2) was shown using three different methods based on the
      binding of a [32P]-labeled 2-5A probe of high specific activity to its binding
      site. Negative Western blotting assay with a specific monoclonal antibody
      correlated the previous findings. RNase-specific mRNA was not detectable even
      after treatment of cells with 1000 units/ml of interferon alpha/beta. This is not
      due to a mutation of the gene because an intronless genomic DNA sequence encoding
      2-5A-binding site was cloned and expressed. It is likely that the expression of 2
      5A-dependent RNase was impaired at the transcriptional level while having the
      known IFN alpha/beta-transcriptional regulatory factors as revealed by induction
      of p69 2-5A-synthetase gene. This may account for a differential activation of 2
      5A-dependent RNase and 2-5A-synthetase genes by type I-interferon, and suggests
      that other members of regulatory transcription factors, different from IRF-1 and
      STAT proteins, may participate in two different interferon alpha/beta signaling
      pathways.

PMID- 9561801
TI  - Phorbol esters down-regulate alpha-fetoprotein gene expression without affecting
      growth in fetal hepatocytes in primary culture.
AB  - The effects of phorbol esters (phorbol-12,13-dibutyrate, PDB) on alpha
      fetoprotein expression and cell growth were assayed by using fetal hepatocytes in
      primary culture. PDB acts synergistically with epidermal growth factor (EGF) to
      specifically decrease alpha-fetoprotein (AFP) mRNA levels, without affecting the
      expression of other genes of the same family, such as albumin and Vitamin D
      binding protein (DBP). This effect is PDB-dose dependent, maximal effects being
      at 10 ng/ml. The implication of protein kinase C (PKC) in this effect seems clear
      since bisindolylmaleimide (BIS), a specific PKC inhibitor, completely blocks the
      PDB effect on AFP expression. Nuclear run-on experiments show that the decrease
      in AFP mRNA levels is mainly due to an inhibition in the transcription rate of
      the gene. Determination of PKC activities shows that fetal hepatocytes contain
      mainly Ca(2+)-independent isoenzymes, which patterns of activation was not
      modified by EGF plus PDB treatment with respect to PDB treatment. We have found
      that MAPK and JNK activities, c-jun and c-fos mRNA levels and AP-1 binding
      activity are notably increased when cells are incubated with both EGF and PDB,
      PDB does not stimulate growth of fetal hepatocytes, measured either as [3H]
      thymidine incorporation into DNA or by cell cycle analysis using flow cytometry.
      All these results suggest that activation of PKC may affect liver gene expression
      rather than cell growth in fetal hepatocytes.

PMID- 9561802
TI  - D1 dopamine receptor activity is not altered by a mutation in the first
      intracellular loop.
AB  - The first intracellular loop of the G protein-coupled receptors (GPCRs) is
      probably the domain that has been studied least. According to the limited data
      available, mutations of this region can increase, decrease or not affect receptor
      G protein coupling, depending on the receptor. Melanocyte-stimulating hormone
      (MSH) receptors with a Ser69Leu mutation of the first intracellular loop
      phenotypically confer tobacco color to the coat of mice, and have constitutive
      activity and enhanced agonist stimulation of adenylyl cyclase. Since the human D1
      dopamine receptor (D1DR) has a serine at the equivalent position, we were
      interested to see if this serine is involved in receptor-G protein coupling in a
      similar fashion. Our site-directed mutagenesis study showed that the replacement
      of this serine by leucine (Ser56Leu) in D1DR did not affect the ability of the
      receptors to bind ligand or couple to G protein.

PMID- 9561803
TI  - Cyclic AMP potentiates substance P-induced amylase secretion by augmenting the
      effect of calcium in the rat parotid acinar cells.
AB  - Potentiation of amylase secretion by the combination of isoproterenol and
      substance P was examined in perfused rat parotid acinar cells. Combined additions
      of substance P and isoproterenol evoked biphasic changes in amylase secretion, an
      initial large peak and the following sustained plateau: the magnitudes of the
      both responses were higher than the sum of the responses induced by each agonist
      alone. Isoproterenol also increased the maximum response and the apparent
      affinity (EC50) for substance P to evoke the initial peak response; the EC50
      values were about 20 and 0.8 nM, respectively, in the absence and the presence of
      isoproterenol. On the other hand, 1 nM substance P was sufficient for evoking the
      maximum potentiation of the sustained plateau response. Substance P did not
      change the EC50 for isoproterenol. The effect of isoproterenol was mimicked with
      dibutyryl cyclic AMP and agonists that increase parotid cyclic AMP. Omission of
      Ca2+ or addition of 5 mM nickel chloride almost completely abolished the
      potentiation of the sustained plateau, but little decreased that of the initial
      peak. Depletion of Ca2+ in InsP3-sensitive intracellular stores with
      thapsigargin, on the other hand, decreased the initial peak response, but not the
      sustained plateau, to substance P. The potentiation was also observed between
      isoproterenol and Ca2+ ionophores. Switching to the solutions containing higher
      concentrations of Ca2+ during the continuous stimulation with isoproterenol or
      IBMX evoked a large, but transient, response of amylase secretion. Time course of
      changes in amylase secretion induced by isoproterenol and substance P in
      combination was very similar to that of substance P, but not of isoproterenol.
      Isoproterenol did not enhance the effect of substance P on [Ca2+]i. These results
      show that the potentiation is mainly, if not totally, caused by cyclic AMP
      induced enhancement of the potency and the efficacy in the pathway regulated by
      Ca2+.

PMID- 9561804
TI  - Vasopressin-induced activation of protein kinase C in renal epithelial cells.
AB  - Recent studies indicate that the actions of arginine vasopressin (AVP) and other
      agonists that stimulate electrogenic sodium transport in renal epithelial A6
      cells are linked to a Ca(2+)-mobilizing signal transduction mechanism that
      involves generation of inositol trisphosphate. Since diacylglycerol is the other
      product in this pathway, studies were performed to determine the possible role of
      PKC in the stimulation of sodium transport. AVP induced a biphasic increase in
      diacylglycerol generation, characterized by an initial rapid rise and then a
      sustained elevation, and PKC activation, reflected by phosphorylation of a
      specific 80 kDa myristoylated alanine-rich PKC substrate (MARCKS). To determine
      the PKC isoform(s) involved in this process, immunoblot analysis was performed
      using antisera that recognize both classical PKC isoforms, XPKC-I and XPCK-II,
      cloned from Xenopus oocytes. The transcripts of both isoforms were expressed in
      the A6 cell. Since protein recognized by antisera was translocated from cytosol
      to the particulate fraction after exposure to AVP, one or both isoforms were
      activated in the A6 cell. Further studies showed that cyclohexyladenosine and
      insulin, additional agonists of sodium transport in A6 cells, also stimulated
      phosphorylation of MARCKS. These results argue that Ca(2+)-dependent PKC is
      involved in the action of AVP, and that of other agonists, which stimulate sodium
      transport.

PMID- 9561805
TI  - Mitogen-activated protein kinase and p70 ribosomal protein S6 kinase are not
      involved in the insulin-dependent stimulation of cAMP phosphodiesterase kinase in
      rat adipocytes.
AB  - To elucidate the mechanism of anti-lipolytic action of insulin in rat epididymal
      adipocytes, we explored the potential mechanism that might be involved in the
      hormone-dependent stimulation of cAMP phosphodiesterase (PDE) kinase. PDE kinase
      was assayed in a cell-free system. Both wortmannin and LY294002, highly specific
      inhibitors of phosphatidylinositol 3-kinase, almost completely blocked the
      hormonal effect not only on PDE kinase but also on mitogen-activated protein
      (MAP) kinase. Neither PD98059, a specific inhibitor of MAP kinase, nor rapamycin,
      a potent inhibitor of insulin-dependent stimulation of p70 ribosomal protein S6
      kinase (p70S6K), had inhibitory effect on that of PDE kinase. These results are
      consistent with the view that (i) insulin-activated PDE kinase as well as MAP
      kinase and p70S6K are localized downstream of phosphatidylinositol 3-kinase, (ii)
      PDE kinase is distinct from either MAP kinase or p70S6K and (iii) PDE kinase does
      not exist downstream of either MAP kinase or p70S6K. It is suggested that PDE
      kinase and MAP kinase or p70S6K may be localized in separate branches of the
      cascade of insulin action. The branching point of the cascade could be either at
      or below the level of phosphatidylinositol 3-kinase.

PMID- 9561806
TI  - Arachidonic acid and human bone marrow stromal cells.
AB  - Human bone marrow stromal cells regulate the growth of marrow hematopoietic
      progenitors by secreting cytokines. Arachidonic acid (AA) is the fatty acid
      precursor of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that modulate the
      growth of human bone marrow progenitors. We have investigated the incorporation
      of AA in human bone marrow stromal cell cultures, their production of PGE2 and
      LTB4 and the effect of AA on their growth. Gas chromatography analysis reveals
      the presence of AA in the human bone marrow plasma and in bone marrow stromal
      cell cultures. In stromal cells, [3H]-AA is incorporated into triglycerides and
      is later delivered into phospholipids. Prelabeling-chase experiments indicate a
      preferential incorporation of AA into phosphatidylethanolamine and no trafficking
      of labeled AA between phospholipid species. Bone marrow stromal cells release
      PGE2 and LTB4 in response to phorbol myristic acetate (PMA) (1 microM) and tumor
      necrosis factor alpha (TNF-alpha) (10 ng/ml). Exogenous AA (up to 1 microM) has
      no significant effect on cell growth. In conclusion, human bone marrow stromal
      cells capt exogenous AA and, thus, may participate to the control of marrow AA
      concentrations. They may also regulate human marrow hematopoiesis by secreting AA
      metabolites such as PGE2 and LTB4.

PMID- 9561807
TI  - Modeling and simulating morphological evolution in an artificial life
      environment.
AB  - This paper presents a computer-based environment designed to study biological
      evolution considering morphological aspects. It was inspired on cellular automata
      and evolutionary algorithm principles. Simple rules are used to determine the
      genotype and phenotype of individuals and their relationships with behavioral
      aspects in a square matrix environment, where individuals can evolve. Two methods
      to simulate mutational errors and to introduce variability of mutations are
      discussed. A series of four simulations show that the model promotes phenotype
      evolution depending on the distribution of food over the environment; morphology
      evolved as to favor movement of the individuals towards the portion of the
      environment in which the food has been distributed or to capture falling food.

PMID- 9561808
TI  - Comparative characterization of the infarcted and reperfused ventricular wall
      muscles by finite element analysis and a myocardial muscle-blood composite model.
AB  - Two methods of characterizing the myocardial fiber bundles' property in the left
      ventricular wall are reviewed: (1) a myocardial muscle-blood composite model
      which assumes the myocardial muscle bundles to be incompressible but allows the
      intramural blood volume fraction to be taken into account, and (2) a two
      dimensional finite element method for inverse determination of the myocardial
      Young's modulus during diastole by matching the computed and tomographically
      imaged cross-sectional areas near the mid-ventricular, short axis of the left
      ventricle at the end of diastole. The first method requires the measurements of
      ventricular wall thickness and the intramural blood volume fraction while the
      second method requires the image cross-sectional shapes and the corresponding
      left ventricular chamber pressures. This paper gives greater details of these two
      methods than in the previously presented progress reports and also presents a
      scheme for comparative characterization of the myocardial properties for an
      initial coronary artery occlusion and subsequent reperfusion study of the
      recently infarcted, left-ventricular wall regions. Furthermore, an attempt is
      made to correlate the data computed by the two methods. This may eventually lead
      to a reduction in the number of the required measurements needed for the two
      methods.

PMID- 9561809
TI  - A computer model of intracranial dynamics integrated to a full-scale patient
      simulator.
AB  - The ability to visualize intracranial dynamics during simulated clinical
      scenarios is a valuable tool for teaching brain physiology and the consequences
      of different medical interventions on the brain. Studies have isolated
      physiologic variables and shown their effects on brain dynamics. However, no
      studies have shown the combined effects of these variables on intracranial
      dynamics. This brain model offers one approach that brings all these
      relationships together and shows how they affect the dynamics of the brain. The
      brain model obtains its physiologic inputs from a full-scale patient simulator
      which responds to clinical interventions. This integration allows individuals
      working on the patient simulator to see the effects of their actions on brain
      dynamics. The brain model gives a real-time display of intracranial events
      (cerebral metabolic rate, cerebral blood flow, cerebral blood volume, cerebral
      perfusion pressure, and intracranial pressure) and responds to changes in the
      pulmonary and cardiovascular condition of the patient simulator.

PMID- 9561810
TI  - SHARE: a tool to analyze and assess strategies in health care organization
      management.
AB  - In health care organizations, management of both human and material resources
      implies decision making. When seemingly equivalent strategies are possible,
      simulation can help to make a decision on better grounds. The SHARE workframe was
      designed to address the specificities of health care and to provide a
      comprehensive environment for modelling and simulating health care processes. The
      typology of objects is defined as Actors, subdivided in Clients and Resources and
      Elementary Operations. Graphical tools allow us to build processes from these
      objects and to create their relationships. Various strategies based on either
      clinical or managerial changes may be investigated. After a simulation, graphical
      tools allow us to display summary information on the utilization of all actors,
      waiting times, and goodness of execution. The use of SHARE is exemplified with
      the analysis and simulation of changes in the Pulmonary Function Testing
      Laboratory of the Saint-Antoine Hospital, Paris.

PMID- 9561811
TI  - Serial VCG/ECG analysis using neural networks.
AB  - Serial ECG analysis is an important diagnostic tool in which two or more
      successive ECG recordings from the same patient are compared in order to find
      changes due to, e.g. myocardial infarction. The present study investigates a new
      approach to serial analysis which is based on artificial neural networks.
      Interrecording changes are sometimes falsely detected due to electrode
      misplacement or positional changes of the heart. In order to compensate for such
      problems, a new technique for VCG loop alignment was employed. A study population
      of 1000 patients with two recordings was used and manually scrutinized by three
      experienced ECG interpreters. Pathological changes indicating newly developed
      infarcts were found in 256 patients. Different combinations of VCG/ECG
      measurements served as input data to the neural network. The best performance of
      the neural network was obtained when ECG and VCG measurements were combined and
      the resulting sensitivity was 69% at a specificity of 90%. The use of only ECG or
      VCG measurements reduced the sensitivity to 63% and 60%, respectively. The
      results indicated that serial analysis based on neural networks did not improve
      significantly when VCG loop alignment was included.

PMID- 9561812
TI  - Urosepsis in the critical care unit.
AB  - Critical care unit patients show a higher risk of developing a bloodstream
      infection than ward patients. The urinary tract is the main source of hospital
      acquired secondary bloodstream infection. Nosocomial urinary tract infection is
      promoted by bladder catheterization in the vast majority of cases. Aerobic gram
      negative bacilli are the prevalent agents of bloodstream infection secondary to a
      nosocomial urinary tract infection. Sepsis and septic shock are severe
      complications of these infections in the critical care patient. Management of
      patients with a septic process of urinary source calls for the combination of
      adequate life-supporting care, an appropriate antibiotic therapy, and innovative
      adjunctive measures. Accurate catheter care is the best measure to adopt for the
      prevention of urosepsis.

PMID- 9561813
TI  - Fulminant hepatic failure.
AB  - Fulminant hepatic failure is a devastating illness that carries considerable
      mortality and affects patients with previously healthy livers. Although the
      etiology of FHF remains unclear in a significant number of cases, viral hepatitis
      and drug-induced liver injury account for the majority of identifiable causes.
      The clinical presentation varies widely, but is always characterized by the
      presence of encephalopathy. Markedly elevated transaminases are seen, but do not
      correlate with extent of liver injury. Prothrombin time, bilirubin, creatinine,
      and arterial pH are prognostic indicators of survival in FHF. FHF and its
      consequences must be readily recognized so that appropriate triage and treatment
      can be administered. All patients should be managed in an intensive care setting
      pending transfer to a liver transplantation center. Supportive care remains the
      mainstay of treatment, with liver transplantation reserved for select patients.

PMID- 9561814
TI  - Antibiotic resistance problems in the critical care unit.
AB  - The increased resistance of bacteria to antimicrobial agents poses major
      therapeutic problems for the treatment of patients hospitalized in critical care
      units. This article discusses the mechanisms of resistance and the basic
      rationale for the treatment of infected patients. The authors also discuss
      methods used to control the dissemination of resistant bacteria from patient to
      patient, the complex problems of colonization, and the strategies used to delay
      the emergence of resistance to new antibiotics.

PMID- 9561815
TI  - Postcardiac surgery infections.
AB  - Infections following cardiac surgery, although generally uncommon, are associated
      with difficult management decisions and significant morbidity and mortality. They
      often present while the patient is either in a critical care unit, or requires
      CCU management. This review analyzes infections related to median sternotomy
      wounds, prosthetic heart valves, transvenous permanent pacemakers, automatic
      implantable cardioverter-defibrillators, and left ventricular assist devices. The
      diagnosis, microbiology, treatment and outcome of each is also discussed.

PMID- 9561816
TI  - Skin and soft tissue infections in critical care.
AB  - Clinicians in the critical care setting see extensive, severe, and often
      necrotizing infection, as well as atypical or unusual infection that can be
      misdiagnosed, resulting in delays in treatment. Greater numbers of
      immunocompromised patients are at risk for both types of infection. A thorough
      understanding of various etiologies and presentations of these infections is
      essential, as is the ability to discriminate between infectious and noninfectious
      etiologies.

PMID- 9561817
TI  - Infections in nonleukopenic compromised hosts (diabetes mellitus, SLE, steroids,
      and asplenia) in critical care.
AB  - Acutely ill patients who are immunocompromised but not neutropenic most commonly
      are: (1) diabetic; (2) on chronic high-dose steroid therapy; (3) have lupus; or
      (4) have impaired or absent splenic function. These patients often present in the
      CCU because of the severity of their infection. Differential diagnosis may be
      approached by first considering the patient's underlying disease, i.e., SLE. The
      next step in the diagnostic process is to appreciate the immune defect associated
      with these disorders. The nature of the immune defect determines which clinical
      pathogens are related to the immune defect. Pathogens are associated with a
      sterotyped pattern of organ involvement. The object of the diagnostic analysis is
      to determine the most likely organism affecting a particular organ system, given
      the defect in host defenses associated with the patient's underlying illness. In
      this way, a useful clinical diagnosis can be made rapidly, and appropriate
      clinical specimens obtained for diagnostic testing. Often empiric therapy must be
      started pending the results of diagnostic testing. In such situations, empiric
      therapy ordinarily is directed against the bacterial pathogens most likely to
      cause disease relevant to the patient's impaired defenses. Specific therapy for
      unusual or exotic pathogens should not be empiric and should be based on
      demonstration of a pathogenic role by the microorganism. In the case of miliary
      tuberculosis or invasive fungal disease, a case may be made for early empiric
      therapy to cover these organisms if there is sufficient clinical suspicion based
      on the presenting signs and symptoms as well as the pattern of organ involvement.
      As with all infections, but particularly in immunocompromised patients, the early
      initiation of appropriate antimicrobial therapy is essential and often life
      saving.

PMID- 9561818
TI  - Antibiotic use in the critical care unit.
AB  - The antimicrobial management of patients in the critical care unit is complex.
      Not only must the clinician be familiar with a number of clinical,
      microbiological, pharmacological, and epidemiological observations but also
      fundamental pharmacodynamic concepts. It is an understanding of these concepts
      that forms the basis for the design of dosing strategies that maximize clinical
      efficacy and minimize toxicity. Antimicrobial selection is further complicated by
      the plethora of new antimicrobial agents available with varying clinical utility.
      Nowhere is this more evident than in the quinolone class of antibiotics. To aid
      the clinician in differentiating between quinolones it now seems reasonable to
      create a classification system akin to the generation grouping applied to the
      cephalosporins. Our classification is based upon the pharmacodynamic principles
      discussed within this article.

PMID- 9561819
TI  - Antibiotic resistance. Control strategies.
AB  - Antibiotic resistance is a worldwide concern. Over the past several decades,
      antibiotic resistance has increased to many respiratory pathogens as well as
      aerobic gram-negative bacilli. Recently, methicillin-resistant Staphylococcus
      aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have become important
      hospital pathogens. Antibiotic resistance is not related to a particular
      antibiotic structure and is not dependent upon mechanism of antibiotic action.
      The volume of use per se does not increase antimicrobial resistance. This article
      discusses control strategies and identifies which antibiotics are associated with
      the emergence of resistant organisms.

PMID- 9561820
TI  - Nosocomial diarrhea.
AB  - Nosocomial diarrheas are an important problem in hospitals, and in critical care
      units in particular. Hospital-acquired diarrhea may be on an infectious or
      noninfectious basis. Common noninfectious causes of nosocomial diarrhea include
      medication-induced changes in the fecal flora or changes secondary to enteral
      hyperalimenation. Infectious causes of nosocomial diarrhea are due to enteric
      pathogens in outbreak situations and virtually all of the causes are due to
      Clostridium difficile. C. difficile is a resident of the human colon and does not
      cause disease if its toxins are not elaborated. Chemotherapeutic agents, and more
      commonly, antibiotics, induce the elaboration of toxin A and B from C. difficile
      in the distal gastrointestinal tract. The spectrum of disease of C. difficile in
      hospitalized patients includes asymptomatic carriage to mild watery diarrhea,
      fulminant and severe diarrhea, and pseudomembranous enterocolitis. The treatment
      of C. difficile diarrhea is usually with oral metronidazole or vancomycin, and C.
      difficile colitis is treated with intravenous metronidazole. Infection control
      measures are necessary to prevent the spread of this sporforming organism within
      the institution since it is capable of surviving in the hospital environment for
      prolonged periods.

PMID- 9561821
TI  - Intravenous line infections.
AB  - Centrally-placed i.v.-line infections are a frequent cause of fever in the
      critical care unit. i.v.-line infection is not usually accompanied by local signs
      of infection, and usually presents as unexplained fever. The diagnosis should be
      considered only after other causes of fever have been ruled out. The likelihood
      of fever being due to i.v.-line infection increases with duration of i.v.
      catheterization. Skin organisms (i.e., Staphylococcus epidermidis/coagulase
      negative staphylococci, and to a lesser extent, Staphylococcus aureus) are the
      usual pathogens in i.v.-line infection. Treatment of i.v.-line infection involves
      removal of the i.v. line/device. Empiric antibiotic therapy directed against gram
      positive cocci/aerobc gram-negative bacilli is usually started after blood
      cultures have been obtained and the removed catheter tip sent for
      semiquantitative culture.

PMID- 9561822
TI  - Biodegradation of the acetanilide herbicides alachlor, metolachlor, and
      propachlor.
AB  - Alachlor, metolachlor, and propachlor are detoxified in biological systems by the
      formation of glutathione-acetanilide conjugates. This conjugation is mediated by
      glutathione-S-transferase, which is present in microorganisms, plants, and
      mammals. Other organic sulfides and inorganic sulfide also react through a
      nucleophilic attack on the 2-chloro group of acetanilide herbicides, but the
      products are only partially characterized. Sorption in soils and sediments is an
      important factor controlling the migration and bioavailability of these
      herbicides, while microbial degradation is the most important factor in
      determining their overall fate in the environment. The biodegradation of alachlor
      and metolachlor is proposed to be only partial and primarily cometabolic, and the
      ring cleavage seems to be slow or insignificant. Propachlor biodegradation has
      been reported to proceed to substantial (> 50%) mineralization of the ring
      structure. Reductive dechlorination may be one of the initial breakdown
      mechanisms under anaerobic conditions. Aerobic and anaerobic transformation
      products vary in their polarity and therefore in soil binding coefficient. A
      catabolic pathway for chloroacetanilide herbicides has not been presented in the
      literature because of the lack of mineralization data under defined cultural
      conditions.

PMID- 9561823
TI  - The biophysics of the gram-negative periplasmic space.
AB  - When subject to an osmotic 'up-shock', water flows outward from bacterial
      cytoplasm of the bacterium. Lipid bilayers can shrink very little in area and
      therefore must wrinkle to accommodate the smaller volume. The usual consequence
      is that all the layers of the cell envelope must become wrinkled together because
      they adhere to each other and must now cover a smaller surface. Plasmolysis
      spaces are formed if the cytoplasmic membrane (CM) separates from the other
      components of the wall. However, because the CM bilayer is essentially an
      incompressible two-dimensional liquid, this constraint restricts the location and
      shape of plasmolysis spaces. With mild up-shocks they form at the pole and around
      constricting regions in the cell. Elsewhere their creation requires the formation
      of endocytotic or exocytotic vesicles. The formation of endocytotic vesicles
      occurs in animal and plant cells as well as in bacterial cells. With stronger up
      shocks tubular structures (Bayer adhesion sites), or other special geometric
      shapes (e.g., Scheie structures) allow the bilayer to surround an irregular
      shaped cytoplast. Periosmotic agents, that is, those that extract water from the
      periplasm as well as the cytoplasm, are molecules such as poly-vinyl-pyrrolidone
      and alpha-cyclodextrin that are too large to pass through the porins in the outer
      membrane. They were found to significantly inhibit the formation of plasmolysis
      spaces. Presumably, they inhibit the plasmolysis process, which requires that
      extracellular fluid enter between the CM and the outer membrane (OM). In the
      extreme case, with the dehydrating action of both osmotic agents and periosmotic
      agents, periplasmic space formation tends to be prevented and a new kind of space
      develops within the cytoplasm. We have designated these as 'cytoplasmic voids'.
      These novel structures are not bounded by lipid bilayers, in contrast to the
      endocytotic vesicles. These new spaces appear to result from the negative turgor
      pressure generated by the application of the combination of osmotic and
      periosmotic agents causing bubble formation. Several ideas in the literature
      about the wall biology (periseptal annuli, leading edge, osmotic pressure in the
      periplasm) are presented and critiqued. The basic criticism of these is that much
      of the phenomena can be explained because of the physics of the phospholipid
      bilayers and osmotic forces and thus does not imply the existence of a special
      control mechanism to regulate growth and division.

PMID- 9561824
TI  - Microbial production of hydrogen: an overview.
AB  - Production of hydrogen by anaerobes, facultative anaerobes, aerobes,
      methylotrophs, and photosynthetic bacteria is possible. Anaerobic Clostridia are
      potential producers and immobilized C. butyricum produces 2 mol H2/mol glucose at
      50% efficiency. Spontaneous production of H2 from formate and glucose by
      immobilized Escherichia coli showed 100% and 60% efficiencies, respectively.
      Enterobactericiae produces H2 at similar efficiency from different
      monosaccharides during growth. Among methylotrophs, methanogenes, rumen bacteria,
      and thermophilic archae, Ruminococcus albus, is promising (2.37 mol/mol glucose).
      Immobilized aerobic Bacillus licheniformis optimally produces 0.7 mol H2/mol
      glucose. Photosynthetic Rhodospirillum rubrum produces 4, 7, and 6 mol of H2 from
      acetate, succinate, and malate, respectively. Excellent productivity (6.2 mol
      H2/mol glucose) by co-cultures of Cellulomonas with a hydrogenase uptake (Hup)
      mutant of R. capsulata on cellulose was found. Cyanobacteria, viz., Anabaena,
      Synechococcus, and Oscillatoria sp., have been studied for photoproduction of H2.
      Immobilized A. cylindrica produces H2 (20 ml/g dry wt/h) continually for 1 year.
      Increased H2 productivity was found for Hup mutant of A. variabilis.
      Synechococcus sp. has a high potential for H2 production in fermentors and
      outdoor cultures. Simultaneous productions of oxychemicals and H2 by Klebseilla
      sp. and by enzymatic methods were also attempted. The fate of H2 biotechnology is
      presumed to be dictated by the stock of fossil fuel and state of pollution in
      future.

PMID- 9561825
TI  - Mechanism of intraocular pressure elevation during hemodialysis.
AB  - PURPOSE: To detect the mechanism of intraocular pressure elevation during
      hemodialysis. METHODS: We measured intraocular pressure, as well as serum
      osmolality and plasma CO2 pressure, every 30 min during hemodialysis, in 5 eyes
      with severely compromised aqueous outflow facility (Group A) from 4 renal failure
      patients. The same measurements were repeated on the same eyes using intravenous
      hyperosmotic Glyceol to prevent a rapid change in serum osmolality. We also
      measured the same parameters on 8 eyes with normal aqueous outflow facility
      (Group B) from 5 patients. The mean +/- SE of percent changes in each parameter
      was used for the statistical analysis. RESULTS: In Group A, the mean percent
      change of intraocular pressure increased significantly after 90 min, with the
      exception of the change at 180 min. The mean percent change of serum osmolality
      decreased significantly after starting dialysis. A negative correlation in the
      mean percent change of intraocular pressure with serum osmolality was detected (r
      = -0.759, r < 0.0001). The administration of intravenous hyperosmotic agent
      prevented significant changes in not only serum osmolality but also intraocular
      pressure. In Group B, the mean percent change in intraocular pressure showed no
      significant difference at any time, although the change in serum osmolality
      decreased significantly. CONCLUSION: A remarkable rise in intraocular pressure
      occurs during hemodialysis in eyes with an impaired aqueous outflow, when serum
      osmolality decreases rapidly.

PMID- 9561826
TI  - Identification, origins and the diurnal role of the principal serine protease
      inhibitors in human tear fluid.
AB  - PURPOSE: Previous work identified polymorphonuclear leukocyte (PMN) elastase as
      the major caseinolytic entity in tears collected after overnight eye closure.
      This study was designed to identify the principal serine protease inhibitors
      (serpins) in tears and to determine their function in the regulation of PMN cell
      proteases on eye closure. METHODS: Reflex and closed eye tear samples were
      collected by microcapillary tube and centrifuged. After reflex and closed eye
      supernatants (R and C) were fractionated by HPLC, samples were subjected to
      casein zymography and reverse zymography. Western blots were utilized to screen
      tears and HPLC fractions for elastase, cathepsin G and proteinase-3 and to obtain
      semi-quantitative data on alpha 1-protease inhibitor (alp1), alpha 1
      antichymotrypsin (alpha 1-Achy), secretory leukocyte protease inhibitor (SLPI),
      elafin and alpha 2-macroglobulin (alpha 2-M) as well as associated complexes and
      products. To confirm specificity of reactivity, samples were immunoprecipitated
      for a given protease or serpin and screened for the coprecipitation of
      interacting species. RESULTS: Although R fluid contains no caseinolytic activity,
      it contains low levels of serpin-like activity principally in the form of SLPI (5
      10 ng/microliter). Lesser amounts of alpha 2-M, alpha 1-Achy and alp1
      (approximately < 1-3 ng/microliter) are also evident. C fluid is associated with
      very high levels of PMN cell proteases along with a approximately 5-20-fold
      increase in the concentrations of all of the above inhibitors. Trace levels of
      elafin were also detected. The concentrations of rapid reacting inhibitors
      exceeded that of proteases, with SLPI, alpha 1-Achy and alp1 being the principal
      functional entities. In atypical samples, complexes of elastase and alpha 2-M
      were also encountered. CONCLUSIONS: SLPI, a known antimicrobial agent and an
      elastase and cathepsin G inhibitor, is the principal serpin in R fluid. C fluid
      is associated with a marked increase in the concentrations of an array of rapid
      reacting serpins capable of inhibiting all known PMN cell serine proteases. In
      the normal closed eye, the concentration of rapid reacting inhibitors always
      exceeds that of proteases with C fluid also containing a functional reserve of
      the slow reacting inhibitor alpha 2-M.

PMID- 9561827
TI  - In vivo morphometry of the lamina cribrosa and its relation to visual field loss
      in glaucoma.
AB  - PURPOSE: The lamina cribrosa has been proposed as a site of origin of the optic
      nerve damage in glaucoma. The purpose of this study was to investigate, in vivo,
      the clinical features of the lamina cribrosa pores of glaucomatous patients and
      to relate their morphometric characteristics to the extent of their visual field
      loss. METHODS: Images of the internal lamina cribrosa surface of 60 glaucomatous
      patients and 15 normal subjects were acquired, in vivo, using a scanning laser
      ophthalmoscope (SLO). A purposely developed technique of image processing was
      employed to objectively evaluate pore morphometry, with particular regard to
      their geometrical characteristics (circularity and elongation). Visual function
      was assessed by automated perimetry (Humphrey Field Analyser). RESULTS: Normal
      subjects showed approximately round lamina pores. In glaucomatous patients, pores
      become more elongated and less circular with increasing field loss (p = 0.009 and
      p < 0.001, respectively). CONCLUSIONS: Scanning laser ophthalmoscopy and a new
      technique of image processing were employed, for the first time, to the
      investigation in vivo of the lamina cribrosa of glaucomatous patients, in
      relation to the extent of visual field loss. The results indicated differences in
      the lamina cribrosa pore morphometry associated with increasing severity of the
      disease. These changes may represent the result of compressing and shearing
      forces applied to the laminar plates.

PMID- 9561828
TI  - Histochemical mapping of NADPH-diaphorase in monkey and human eyes.
AB  - PURPOSE: To localize nicotinamide adenine dinucleotide phosphate-diaphorase
      (NADPH-d) in normal human and monkey eyes. METHODS: NADPH-d activity in ocular
      tissue sections was revealed by histochemical staining. RESULTS: NADPH-d staining
      was found in the anterior and posterior ocular segment of both species. In the
      anterior segment, reaction product was present in the corneal epithelium and
      endothelium, iris dilator and sphincter, lens capsule, ciliary muscle, and non
      pigmented epithelial cells and stroma of the ciliary processes. Staining density
      in the longitudinal ciliary muscle was higher than in the other ciliary muscle
      regions in the human; such regionalization was less apparent in the monkey. The
      trabecular meshwork stained minimally if at all in both species. In the posterior
      segment, staining was seen around choroidal blood vessels and choroidal nerves,
      and in the retinal pigment epithelial, photoreceptor, bipolar, inner plexiform
      and ganglion cell layers. CONCLUSIONS: NADPH-d is widespread in human and monkey
      eyes, indicating significant and presumably functionally relevant NO production
      in the various ocular structures.

PMID- 9561829
TI  - Hyperopia is predominantly axial in nature.
AB  - PURPOSE: Myopia has been found to be predominantly axial in nature, i.e. myopic
      eyes have longer than normal axial lengths, with corneal radius variations having
      only a small influence on the magnitude of the refractive error. In this study we
      assess whether a similar relationship exists for hyperopia. METHODS: Biometric
      data were collected on 57 subjects with either emmetropic or hyperopic refractive
      errors ranging in magnitude from -0.37 D to +17.25 D. Our main analysis
      concentrated on subjects with less than +10 D of hyperopia (group 1, n = 53), as
      subjects with +10 D of hyperopia or more (group 2, n = 4) exhibited marked
      differences in their biometric characteristics. RESULTS: Analysis of group 1 data
      revealed a significant relationship (r2 = 0.611, p = 0.0001) between the degree
      of hyperopia and the measured axial lengths. A weak but statistically significant
      relationship (r2 = 0.128, p = 0.009) was also found between mean corneal radius
      measures and mean spherical refractive errors, with the mean corneal radius
      flattening with increasing hyperopia. In group 2, three of the four subjects
      exhibited much steeper corneal characteristics than predicted from the group 1
      data. CONCLUSIONS: Our results suggest that hyperopia, like myopia, is
      predominantly axial in nature, although the corneal radius also plays a role in
      determining refractive error magnitude. These results have implications for
      refractive surgery and visual performance in hyperopic eyes.

PMID- 9561830
TI  - Effects of hypoxia and post-hypoxic recovery on chick retinal pigment epithelium
      potentials and light-evoked responses in vitro.
AB  - PURPOSE: To determine the cellular mechanisms involved in the hypoxia-induced
      alteration of the retinal pigment epithelium (RPE) potentials and the light
      evoked responses of the RPE in chicks. In addition, to determine the mechanisms
      involved in the recovery of the RPE during the post-hypoxic period. METHODS: In
      vitro preparations of chick retina-RPE-choroid were studied by potassium
      selective microelectrodes placed in the subretinal space. In addition, single
      barrel microelectrodes were used to obtain intracellular recordings from the RPE
      cells. The perfusate was bubbled continuously with 95% oxygen and 5% carbon
      dioxide for the control condition and replaced by 95% nitrogen and 5% carbon
      dioxide to induce hypoxia. RESULTS: Hypoxia induced a significant reduction of
      the trans-tissue potential which was found to result from the depolarization of
      the apical membrane of the RPE. This depolarization was induced by an increase of
      subretinal [K+]o. The c-wave was also markedly decreased or abolished during
      hypoxia. There were two phases of post-hypoxic recovery: an initial small
      increase in the trans-tissue potential resulting from a basal membrane
      depolarization followed by an apical membrane hyperpolarization. The trans-tissue
      potential and the c-wave also were supernormal in two phases during this post
      hypoxic period. The c-wave amplitude was temporarily elevated (263.7 +/- 77.4% of
      pre-hypoxic control) because of the enhanced trans-epithelial c-wave and without
      a light-evoked decrease in subretinal [K+]o. CONCLUSIONS: The trans-tissue
      potential and the c-wave were markedly decreased during hypoxia. During the post
      hypoxic period, both potential recovered with transient supernormalities in two
      phases. The results suggested that the hypoxic changes resulted directly from
      changes of the RPE membranes and indirectly from a change in the subretinal [K+]o
      but were not mediated by the light-evoked decrease in subretinal [K+]o.

PMID- 9561831
TI  - Culture of human retinal pigment epithelial cells from peripheral scleral flap
      biopsies.
AB  - PURPOSE: We studied various methods for harvesting retinal pigment epithelium
      (RPE) biopsies from cadaver human eyes of donors over age 60 years. Our goal was
      to harvest cells for possible autologous RPE cell transplantation in patients
      with age-related macular degeneration and to test the viability of the RPE after
      isolation by evaluating explant growth in culture. METHODS: Choroid-RPE biopsies
      were excised from enucleated human eyes. The RPE was separated from the choroid
      by treatment with type IV collagenase. RPE patches were cultured. After 100-500
      cells had grown out from the explant, the primary cultures were passaged.
      RESULTS: There was no clear effect of donor age on the ability to establish
      primary RPE cultures with good morphology from biopsies 2 x 2-10 x 10 mm2 in
      size. Biopsies 6 x 6 mm2 or larger produced satisfactory primary cultures more
      than 70% of the time. The number of viable RPE cells (defined as the number of
      cells adherent to the culture dish 24 h after plating) obtained after enzymatic
      separation of the RPE and choroid was an important determinant of our ability to
      establish primary cultures and passage the cells. Primary cultures with good
      cellular morphology were obtained 100% of the time when RPE explants > 4 mm2 in
      size were obtained from the biopsy specimen. Seventy-three percent of the
      biopsies yielding explants > 4 mm2 in size were successfully passaged.
      CONCLUSIONS: These results suggest that peripheral scleral flap biopsies in aging
      donors can be used to establish RPE explant primary cultures. These cultures may
      be suitable as a source for autologous RPE transplantation in patients.

PMID- 9561832
TI  - Spectrum of pathogenic mitochondrial DNA mutations and clinical features in
      Japanese families with Leber's hereditary optic neuropathy.
AB  - PURPOSE: To investigate the incidence and clinical significance of primary or
      proposed secondary mitochondrial DNA (mtDNA) mutations in Japanese patients with
      Leber's hereditary optic neuropathy (LHON). METHODS: Blood samples from the 80
      unrelated Japanese patients with bilateral optic atrophy were screened for
      primary LHON mutations. Patients found to have a primary LHON mutation were then
      tested for 9 proposed secondary LHON mutations. We investigated the association
      between these mutations and clinical characteristics. RESULTS: Primary mtDNA
      mutations were identified in 68 patients: at np 3460 in 3 (4%) of 68 patients, at
      np 11,778 in 59 patients (87%), and at np 14,484 in 6 patients (9%). We
      identified 5 secondary mtDNA mutations (at np 3394, 4216, 7444, 9438 or 13,708)
      in 10 (15%) of 68 LHON patients and 3 mutations (at np 3394, 4216 or 3708) in 6
      (7%) of 90 healthy Japanese individuals. No patient was positive for more than
      one secondary mutation. The frequency of secondary mutations was similar in the
      68 LHON patients and 90 controls. The clinical features of the Japanese patients
      with any of the 3 primary LHON mutations were similar to those of Caucasian
      patients, despite different mtDNA backgrounds in these populations. The
      percentage of patients with familial LHON harboring the 3460 or 14,484 mutations
      was lower in the Japanese population. CONCLUSIONS: Japanese patients with LHON
      exhibited a very high incidence (87%) of the 11,778 primary mutation. Most of the
      proposed secondary LHON mutations were rare in the Japanese population and they,
      except the 7444 mutation, may not influence the clinical features of LHON.

PMID- 9561833
TI  - Intermediate filament cytoskeletal proteins associated with bovine lens native
      membrane fractions.
AB  - PURPOSE: To examine the intermediate filament cytoskeletal proteins associated
      with native membrane fractions isolated from bovine lenses. METHODS: Decapsulated
      bovine lenses were divided into cortex and nucleus. The lens regions were
      homogenized and separated into water-soluble and water-insoluble fractions by
      centrifugation. Sedimenting membrane fractions were isolated from the water
      insoluble fraction by discontinuous sucrose-density-gradient centrifugation and
      the non-sedimenting membrane fractions were isolated from the Kbr high-density
      water-soluble fractions by flotation, during overnight centrifugation. The
      intermediate filament peptides of the membrane fractions were examined by Western
      blot analysis, using monoclonal antibodies to filensin, cytoskeletal protein 49
      (CP49) and vimentin. RESULTS: Filensin immunoreactive peptides were found in all
      membrane fractions of both cortex and nucleus. The parent 115 kDa filensin was
      found almost exclusively in the urea-soluble protein of cortical membrane
      fractions, and was the predominant filensin immunoreactive peptide only in the
      urea-soluble protein of the cortical sedimenting membrane fraction isolated from
      the 25%/45% sucrose density interface. The predominant filensin immunoreactive
      peptide of all other samples migrated with a M(r) of 53 kDa. CP49 immunoreactive
      peptides were found almost exclusively in the urea-soluble protein of all
      membrane fractions from both the cortex and nucleus. The cortical non-sedimenting
      membrane fraction and the nuclear membrane fraction of the 25%/45% sucrose
      density interface were notably deficient in CP49. Vimentin immunoreactive
      peptides were found in both urea-soluble and urea-insoluble proteins of membrane
      fractions from the cortex only. Vimentin was particularly enriched in the
      cortical non-sedimenting membrane fraction. The urea-insoluble filensin
      immunoreactive peptides were only partially removed by alkali extraction,
      indicating a very avid association with the membrane. Two dimensional
      electrophoresis revealed that the urea-soluble protein of the major cortical
      membrane fraction contained two different filensin-derived 53 kDa fragments.
      CONCLUSIONS: The non-sedimenting membrane fraction, which may reflect a distinct
      domain of the lens plasma membrane, possesses a membrane-associated cytoskeletal
      composition different from that of the major sedimenting membrane fractions.

PMID- 9561835
TI  - Marrow-derived activated macrophages are required during the effector phase of
      experimental autoimmune uveoretinitis in rats.
AB  - PURPOSE: Experimental autoimmune uveoretinitis (EAU), an established model for
      human endogenous (autoimmune) posterior uveitis, is a CD4+ T cell-mediated
      disease inducible in Lewis rats by intradermal inoculation with retinal antigens.
      Immunohistochemical studies have previously documented the lymphocyte profiles
      during various stages of the disease process. The purpose of the present study
      was to investigate the role of macrophages in EAU. METHODS: EAU was induced in
      Lewis rats, and the effect of macrophage depletion, using the drug
      dichlorodimethylene diphosphonate (Cl2MDP) encapsulated in liposomes and
      administered intravenously, was assessed based on the clinical and histological
      profile of the disease. RESULTS: The results have shown that in control animals
      macrophages occur early, feature prominently throughout the course of the disease
      and display considerable heterogeneity: marrow-derived ED1+ cells and ED3+ cells
      are the major infiltrating cells, with many cells also expressing ED7 and ED8. In
      contrast, few cells expressed the ED2 antigen during EAU, even though ED2+
      "resident" macrophages occur in the normal choroid. Macrophage depletion, using
      intravenously injected dichloromethylene diphosphonate (Cl2MDP) enclosed in
      liposomes, caused a delay in the onset and a reduction in the severity of EAU
      when administered during the "effector" stage of the disease, i.e. 9-11 days
      after inoculation with retinal antigen. The delay in disease onset was greater
      when liposomes were mannosylated and was accompanied by a reduction in the
      overall inflammatory cell infiltrate into the eye and reduced tissue damage. In
      addition, there was a reduction in the level of expression of MHC Class II
      antigen and CR3 (ED7) antigen, a marker of macrophage activation, in Cl2MDP
      treated animals compared to controls. CONCLUSION: These results suggest that
      blood-borne, activated macrophages are major effectors of tissue damage during
      EAU.

PMID- 9561834
TI  - Histopathological effects of topical ophthalmic preservatives on rat
      corneoconjunctival surface.
AB  - PURPOSE: Long term use of topical drugs has clearly been shown to induce toxic
      immunopathological changes in the ocular surface. However, little is known
      concerning the respective roles of active compounds and preservatives.
      Benzalkonium chloride (BAC) is the most used preservative and its cytotoxicity is
      well known, but other preservatives have not yet been clearly evaluated. We thus
      performed a comparative study to investigate toxic side effects induced in the
      rat ocular surface by applications of various preservatives, with special
      attention to inflammatory infiltrates. METHODS: A total of 35 brown Norway rats
      were divided into seven groups of five each. They received, for one month, in
      both eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chloride, 0.01%
      benzododecinium bromide, 0.004% thiomersal, 0.05% methyl parahydroxybenzoate or
      phosphate-buffered saline (PBS), the last group remaining untreated. Then,
      animals were sacrificed and eyes were processed for histological and
      immunological procedures with monoclonal antibodies to rat immunocompetent cells.
      RESULTS: When compared to controls, all preservative-treated eyes consistently
      showed corneal and conjunctival damage, including epithelial alterations, various
      degrees of keratinization and inflammatory infiltrates at the limbus and within
      the conjunctival stroma and epithelium. No difference was found between the five
      tested drugs. CONCLUSIONS: This study confirms that most preservatives used in
      ophthalmic eyedrops may similarly induce strong histopathological and
      inflammatory changes in the ocular surface after short term use. Although
      obtained in animal model, these results confirm strong toxic side effects in
      patients with preexisting ocular surface disorders and/or receiving topical drugs
      for long periods.

PMID- 9561836
TI  - Nonperfusion of retina and choroid in transgenic mouse models of sickle cell
      disease.
AB  - PURPOSE: To determine if vascular occlusion and nonperfusion is associated with
      the outer retinal atrophy, retinopathy, and choroidopathy (chorioretinopathy)
      that occurs in the alpha H beta S[beta MDD] and alpha H beta S [alpha MD beta
      MDD] transgenic mouse models of sickle cell disease. METHODS: Mice from the alpha
      H beta S[beta MDD] and alpha H beta S[alpha MD beta MDD] transgenic mouse lines
      that express high levels of human beta S globin were anesthetized and
      administered horseradish peroxidase (HRP) intracardially. After 1 min, the
      animals were sacrificed, and the retina from one eye was excised, fixed, and
      developed in diaminobenzidine (DAB). The contralateral eye was fixed, embedded
      whole in glycol methacrylate, and HRP developed in 2.5 microns sections. RESULTS:
      HRP reaction product (HRP-RP) and stained erythrocytes (RBCs) (due to endogenous
      peroxidase) were diffusely distributed within all vascular lumens in flatmount
      retinas from control animals (littermates homozygous for the mouse Beta Major
      deletion not expressing the beta S transgene). In 42.5% of the transgenic mice
      expressing beta S without any proliferative retinopathy, many blood vessels
      contained RBC plugs and lacked lumenal HRP-RP. In addition to packed RBCs, fibrin
      was sometimes present at sites of occlusion. In sections from whole eyes of the
      same animals, foci of photoreceptor degeneration were associated with areas of
      choriocapillaris nonperfusion (lumen that lacked HRP-PR). In areas with normal
      photoreceptors, the choriocapillaris appeared perfused (HRP-RP was present). In
      animals with proliferative chorioretinopathy, some neovascular formations lacked
      luminal HRP-RP, suggesting autoinfarction. CONCLUSIONS: Nonperfused retinal and
      choroidal vessels were observed in mice from the alpha H beta S[beta MDD] and
      alpha H beta S[alpha MD beta MDD] lines without retinal and choroidal
      neovascularization, whereas, all mice with neovascularization had nonperfused
      areas. Furthermore, small foci of PR loss were associated with areas of
      nonperfused choriocapillaris. These results suggest that sickle cell-mediated
      vaso-occlusions are an initial event in the chorioretinopathy and outer retinal
      atrophy that occurs in these models.

PMID- 9561837
TI  - Immunolocalization of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in human subconjunctival tissues.
AB  - PURPOSE: To evaluate the roles of fibroblast proteins in the remodeling of the
      subconjunctival connective tissue, we immunohistochemically assessed the
      expression of matrix metalloproteinases (MMP)-1 and -2, and the tissue inhibitors
      of matrix metalloproteinases (TIMP)-1 and -2 in cultured human subconjunctival
      fibroblasts and in normal and healing human subconjunctival connective tissue.
      METHODS: Cultured fibroblasts derived from human subconjunctival connective
      tissue and surgical specimens of normal and healing conjunctiva were
      immunostained with monoclonal antibodies directed against human MMPs and TIMPs
      and examined by light and electron microscopy. RESULTS: In the cultured
      fibroblasts, MMP-1 and TIMP-1 antibodies stained the cytoplasm in a fine granular
      pattern, suggesting localization of those proteins in the endoplasmic reticulum
      (ER) and Golgi apparatus. Antibodies to MMP-2 and TIMP-2 reacted with fibroblast
      cytoplasm in a granular pattern. Electron microscopy of those fibroblasts
      revealed MMP-1 and TIMP-1 immunoreactivity in the ER cisternae or on the membrane
      of the ER. In surgical samples, MMP-1 and TIMP-1 were immunohistochemically
      detected in healing subconjunctival tissue, but not in conjunctival epithelium or
      normal subconjunctival tissue. CONCLUSIONS: MMPs and TIMPs may be involved in
      remodeling of subconjunctival connective tissue and in fibroblast population
      after surgical interventions. These proteins may play a crucial role in the post
      operative fibrotic process occurring during scar formation in subconjunctival
      tissue.

PMID- 9561838
TI  - Cell regulation web alert.

PMID- 9561839
TI  - Signaling angiogenesis and lymphangiogenesis.
AB  - Exciting progress has been made in elucidating the complex network of receptor
      ligand interactions that regulate blood vessel growth. Understanding these
      control mechanisms is of interest not only because of their role in developmental
      biology, but because they provide potential therapeutic strategies for disease
      processes involving angiogenesis, such as tumor growth.

PMID- 9561840
TI  - Transcriptional control of adipogenesis.
AB  - Adipocyte differentiation is coordinatedly regulated by several transcription
      factors. C/EBP beta, C/EBP delta and ADD-1/SREBP-1 are active early during the
      differentiation process and induce the expression and/or activity of the
      peroxisome proliferator activated receptor-gamma (PPAR gamma), the pivotal
      coordinator of the adipocyte differentiation process. Activated PPAR gamma
      induces exit from the cell cycle and triggers the expression of adipocyte
      specific genes, resulting in increased delivery of energy to the cells. C/EBP
      alpha, whose expression coincides with the later stages of differentiation,
      cooperates with PPAR gamma in inducing additional target genes and sustains a
      high level of PPAR gamma in the mature adipocyte as part of a feedforward loop.
      Altered activity and/or expression of these transcription factors might underlie
      the pathogenesis of disorders characterized by increased or decreased adipose
      tissue depots.

PMID- 9561841
TI  - Protein tyrosine phosphatases in the developing nervous system.
AB  - Protein tyrosine phosphatases (PTPs) constitute a diverse family of intracellular
      and transmembrane proteins. Expression data and recent genetic analyses indicate
      that many PTPs play important roles in different aspects of nervous system
      development. Although PTP mechanisms are still poorly understood, current data
      suggest considerable complexity in these signaling pathways.

PMID- 9561842
TI  - Wnt signaling: why is everything so negative?
AB  - The Wnt proteins constitute a family of secreted glycoproteins the members of
      which have essential signaling roles during embryogenesis. The recent
      identification of several new regulators of this signal transduction pathway have
      revealed unexpectedly intricate levels of constraint on Wnt-dependent gene
      activation, and studies in developing embryos and in cell culture systems have
      allowed a more complete understanding of the functional and biochemical
      interactions between components of this evolutionarily conserved pathway.

PMID- 9561843
TI  - Mads and Smads in TGF beta signalling.
AB  - The discovery of the Mothers against dpp (Mad) gene in Drosophila has opened a
      window on an entirely unique signalling pathway that functions to mediate
      responses to the tumour growth factor beta (TGF beta) superfamily. This pathway,
      which is comprised of a family of proteins related to Mad, acts to convey signals
      directly from TGF beta receptors to the nucleus and is implicated in the
      pathogenesis of human diseases.

PMID- 9561844
TI  - Analysis of antigen receptor signalling using mouse gene targeting.
AB  - Gene targeting in mice has enabled the study of antigen receptor signalling in
      primary lymphocytes. Furthermore, it has provided the tools to directly assess
      the function of individual signalling proteins by mutation of the genes that code
      for them. Some of the results that gene targeting has produced have confirmed
      previous views of the function of particular proteins. Others have given
      surprising results and overturned accepted viewpoints.

PMID- 9561845
TI  - Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to
      development.
AB  - The c-Jun amino-terminal kinase (JNK) group of MAP kinases has been identified in
      mammals and insects. JNK is activated by exposure of cells to cytokines or
      environmental stress, indicating that this signaling pathway may contribute to
      inflammatory responses. Genetic and biochemical studies demonstrate that this
      signaling pathway also regulates cellular proliferation, apoptosis, and tissue
      morphogenesis. A functional role for JNK is therefore established in both the
      cellular response to stress and in many normal physiological processes.

PMID- 9561846
TI  - Integrin signaling and cell growth control.
AB  - Integrins contribute to cell growth by providing a physical linkage between
      cytoskeletal structures and the extracellular matrix, and also by participating
      in various signal transduction processes. The interaction of integrins with
      matrix ligands can generate signals in and of itself, and can also modulate
      signals instigated by soluble factors such as peptide mitogens. Cellular events
      affected by integrin-mediated signaling include motility, cell division,
      differentiation and programmed cell death. Elucidation of how integrin-mediated
      cell adhesion controls cell growth is likely to be of fundamental importance in
      understanding complex biological processes, such as tissue morphogenesis and
      tumor progression.

PMID- 9561847
TI  - Cellular control lies in the balance of forces.
AB  - Mechanical tension generated within the cytoskeleton of living cells is emerging
      as a critical regulator of biological function in diverse situations ranging from
      the control of chromosome movement to the morphogenesis of the vertebrate brain.
      In this article, we review recent advances that have been made in terms of
      understanding how cells generate, transmit and sense mechanical tension, as well
      as how they use these forces to control their shape and behavior. An integrated
      view of cell regulation that incorporates mechanics and structure as well as
      chemistry is beginning to emerge.

PMID- 9561848
TI  - Cellular responses to DNA damage.
AB  - The exposure of cells to DNA damage inducers triggers a wide range of cellular
      responses including an alteration in gene expression, a delay in cell-cycle
      progression and the stimulation of DNA repair. In multicellular organisms, DNA
      damage can also activate programmed cell death. Recently, several signaling
      pathways that link DNA damage to gene expression and to the cell-cycle
      checkpoints have been identified. These pathways establish a framework for future
      studies of DNA damage responses.

PMID- 9561849
TI  - Oxygen radicals and signaling.
AB  - Recent evidence suggests that reactive oxygen species, such as superoxide anions
      and hydrogen peroxide, function as intracellular second messengers. This review
      will discuss the progress in understanding the intracellular pathways leading
      from ligand stimulation to the generation of oxidants, as well as some of the
      increasing number of cellular processes that appear to be subject to redox
      regulation.

PMID- 9561850
TI  - The synthesis and cellular roles of phosphatidylinositol 4,5-bisphosphate.
AB  - Phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2) is a membrane phospholipid
      found in all eukaryotic cells which regulates many important cellular processes,
      including organization of the cytoskeleton, vesicular trafficking and platelet
      activation. PtdIns 4,5-P2 can either act as a substrate for lipid kinases and
      phosphatases, or directly interact with proteins. Recent work has focused on the
      characterization of the enzymes that regulate PtdIns 4,5-P2 levels in the cell.
      The discovery of proteins whose activities are modified by interaction with
      PtdIns 4,5-P2 has helped to redefine the role of this lipid in cell biology.

PMID- 9561851
TI  - Mechanisms and consequences of activation of protein kinase B/Akt.
AB  - Protein kinase B (PKB)/Akt is a growth-factor-regulated serine/threonine kinase
      which contains a pleckstrin homology domain. Binding of phosphoinositide 3-OH
      kinase products to the pleckstrin homology domain results in translocation of
      PKB/Akt to the plasma membrane where it is activated by phosphorylation by
      upstream kinases including the phosphoinoside-dependent kinase 1 (PDK1).
      Activated PKB/Akt provides a survival signal that protects cells from apoptosis
      induced by various stresses, and also mediates a number of metabolic effects of
      insulin.

PMID- 9561852
TI  - The mRNA 5' cap-binding protein eIF4E and control of cell growth.
AB  - Control of gene expression at the translational level is important in cell growth
      and proliferation. Recent work has identified pathways that transmit signals from
      extracellular stimuli to several translation components. A key participant in
      regulation of translation is eIF4E, the mRNA 5' cap-binding protein. Several
      signalling pathways impact on the activity of eIF4E. This review will summarise
      recent findings on the MAP kinase signalling pathway that leads to
      phosphorylation of eIF4E and on pathways that regulate repression of eIF4E
      function. A major unresolved question is how the changes in translation modulate
      cell growth rate, and a working model will be discussed.

PMID- 9561853
TI  - Interaction of invasive bacteria with host signaling pathways.
AB  - Many bacterial pathogens exploit mammalian cell functions in order to promote
      their adherence to or uptake by host cells. Recent work has led to the
      identification of some of the bacterial and mammalian proteins involved in these
      processes. Although specific mechanisms differ among pathogens, a common aspect
      appears to be regulation of signaling pathways that control the actin
      cytoskeleton.

PMID- 9561854
TI  - Therapeutic intervention and signaling.
AB  - Significant advances in our understanding of intracellular signal transduction
      pathways have emerged within the past several years. It is now apparent that,
      under certain circumstances, particular isoforms of Ras can be prenylated by
      geranylgeranyl protein transferase as well as farnesyl protein transferase. New
      pathways controlling growth factor-dependent inhibition of apoptosis involving
      phosphoinositide 3'-hydroxykinase and the protein kinase Akt have also been
      clarified.

PMID- 9561855
TI  - Neurohistological changes after facial nerve rerouting.
AB  - The present study was devised to examine possible structural changes in the
      facial nerve after rerouting. Changes were studied in 20 adult guinea pigs using
      different stains for the different nerve structures. Animals were anesthetized
      and the facial nerve rerouted. The animals were then separated into two groups,
      an "early" group killed after 7 days and a "late" groups after 15 days. The
      rerouted facial nerve was sectioned and stained to determine what structural
      changes had taken place. In both groups there were marked changes in the axons,
      Schwann cells and connective tissue elements, as well as a marked cellular
      infiltrate. Although these latter changes in the late group were slightly less
      than in the early group, the reticulin network was much thicker and there was
      greater disruption of the nerve bundles. These findings show that facial nerve
      rerouting causes significant structural changes that may persist for variable
      periods after surgery. Any attempts at facial rehabilitation clinically should be
      delayed to allow enough time for nerve function to recover.

PMID- 9561856
TI  - The vascular mechanism of action of betahistine in the inner ear of the guinea
      pig.
AB  - The aim of this study was to investigate the mechanism and site of action of
      betahistine dihydrochloride in the inner ear of the guinea pig. Betahistine
      evoked increases in cochlear blood flow (CBF) have been presumed to be due to the
      drug effect on the later wall capillary bed or larger feeding vessels in the
      cochlea vascular system. As such, the mechanism of action could be due to
      inhibition of H3 receptors. Betahistine may also have a direct effect on
      postsynaptic H1/H2 receptors and/or an effect modulated by other autonomic
      receptors. Betahistine-evoked CBF responses were assessed by laser Doppler
      flowmetry in the presence of an H3 agonist (alpha N-methyl-histamine
      dihydrochloride), an H3 antagonist (thioperamide), an H2 antagonist (cimetidine)
      or an alpha 2 antagonist (idazoxan). The effects of betahistine on circulation in
      the anterior inferior cerebellar artery (AICA) and ipsilateral stria vascularis
      (SV) were assessed using intravital microscopy (IVM). Findings showed that
      betahistine increased CBF and reduced systemic blood pressure (BP). In contrast,
      alpha N-methylhistamine dihydrochloride had no effect on baseline CBF or BP and
      did not influence betahistine-induced increases in CBF. Thioperamide reversed the
      effects of betahistine on CBF, but had no effect on baseline CBF or BP.
      Cimetidine had no marked effect on baseline CBF or betahistine-induced increases
      in CBF Idazoxan had no consistent effects on baseline CBF, but abolished the
      effect of betahistine on CBF. The mean increase of red blood cell velocity in SV
      capillaries was 15% and occurred without a demonstrable change in capillary
      diameters. In contrast, the diameter of the AICA increased by 17-20%, indicating
      that betahistine-evoked increases in CBF resulted primarily from vasodilatation
      of the AICA. We suggest that this effect may be mediated via presynaptic H3
      heteroreceptors and autonomic alpha 2 receptors.

PMID- 9561857
TI  - Acoustic neuroma surgery and delayed facial palsy.
AB  - Delayed onset of facial palsy is possibly an underestimated but distressing
      complication of acoustic neuroma surgery. The incidence of this complication
      reported in the literature has varied from 11.7 to 41%. This study reviewed
      retrospectively 60 primary acoustic neuroma surgeries performed by a single
      neurotologist. The delayed onset of facial dysfunction was defined according to
      the guidelines described by of Lalwani Butt, Jackler, Pitts and Jingling in 1995.
      They considered either a deterioration of facial function from normal to abnormal
      or an increased severity of the degree of facial paralysis, which was grouped
      using the House-Brackmann scale system. Fifteen of the 60 patients (25%) were
      found to have a deterioration of facial function. The incidence of delayed facial
      palsy was not influenced by age, sex or tumor size. The majority of the patients
      had a favorable prognosis. Only three patients had a grade III-IV facial function
      at 1 year. It is possible that these latter cases might have benefited from
      intraoperative meatal facial nerve decompression, as advocated by Sargent,
      Kartush and Graham.

PMID- 9561859
TI  - Nasal foreign bodies in children.
AB  - Between 1994 and 1997, a total of 72 nasal foreign bodies were removed from 68
      children (28 girls and 40 boys, including 2 repeats) in the ENT Department at
      Robert Debre Hospital, Paris. Ages ranged from 1 to 12.5 years (median, 3 years).
      Two children had bilateral foreign bodies. The unilateral foreign bodies were on
      the right side in 67.6% of cases. The most frequent objects were plastic objects,
      beads, paper, cotton and foam. Insertion was witnessed by an adult or reported by
      the child himself in the majority of cases. The other cases were diagnosed when
      complications occurred (as seen by persistent rhinorrhea and a foul body odor).
      All foreign bodies were removed in the consultation room using a hook or nasal
      forceps.

PMID- 9561858
TI  - Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside
      treatment.
AB  - Although aminoglycosides have been investigated for their cochleotoxicity, it has
      still not been determined whether apoptosis or necrosis results in cochlear hair
      cell death following aminoglycoside treatment. To study possible mechanisms of
      cell death, we used in situ DNA break-labeling to examine guinea pig cochleae
      affected by Kanamycin ototoxicity. Chronic kanamycin treatment induced DNA
      fragmentation that was detectable in both outer and inner hair cells, suggesting
      the occurrence of apoptosis. These findings suggest that apoptosis achieves
      deletion of affected hair cells without disrupting tissue architecture in the
      organ of Corti.

PMID- 9561860
TI  - Ciliary beat frequency of human sphenoid sinus mucosa after cryopreservation.
AB  - In vitro studies of human ciliary activity require relatively large quantities of
      specimens of healthy ciliated epithelium. For this reason we investigated whether
      cryopreserved healthy mucosa taken from the sphenoid sinus during pituitary
      surgery would meet the demands of this type of study. The sinus mucosa from ten
      patients was immersed in two different cryopreservatives. One solution contained
      10% dimethylsulfoxide (DMSO) as cryoprotector. The other contained glycerol as a
      part of human sperm preservation medium (HSPM). The ciliary beat frequency (CBF)
      was measured sequentially by a photoelectrical method: when specimens were fresh
      and then at intervals of 1 week, 1 month and 3 months after cryopreservation in
      liquid nitrogen and thawing. Mean CBF values recorded after thawing did not
      differ significantly from the values measured before cryopreservation. Prior to
      cryopreservation and after thawing, CBF did not change during a period of 4 h.
      Epithelia preserved in DMSO demonstrated that the low mean CBF (5.4 Hz) found was
      caused by a reversible ciliostatic effect of the medium. After thawing and
      rinsing with a neutral medium, CBF showed normal values. We conclude that
      sphenoid sinus mucosa is an appropriate source of ciliated mucosa for in vitro
      experiments. Since non-pathological ciliated epithelium can be maintained in a
      "mucosa bank," our finding makes further studies of CBF of normal human
      respiratory epithelium in vitro a realistic goal.

PMID- 9561861
TI  - Clinical presentation of a sphenochoanal polyp.
AB  - Although choanal polyps frequently arise from the maxillary sinus, a choanal
      polyp originating from the sphenoid sinus is a rare entity. In this report, an
      unusual case of a large choanal polyp taking origin from the sphenoid sinus is
      presented. The reasons for its development and methods of management are
      discussed.

PMID- 9561862
TI  - Topographical anatomy and oncologic implications of the anterolateral surface of
      the arytenoid cartilage.
AB  - The normal topographic relationships of the anterolateral surface of the
      arytenoid cartilage (ALSAC) were reinvestigated with special regard to possible
      implications involving the extensions of local cancer. Serial plastinated whole
      organ sections of 34 normal adult larynges were examined. A cartilaginous crest
      subdivided the ALSAC into a cranial triangular fossa and a caudal oblong fossa
      and provided attachment to the lateral fibers of the vocal cord. The
      thyroarytenoid muscle was mainly anchored within the oblong fossa, but a few
      lateral muscle fibers extended further cranial ward along the ALSAC. The
      triangular fossa was the area of fixation of the vestibular ligament and was
      filled with adipose tissue as well as mucous glands grouped together by strong
      collagenous fiber septa. These septa revealed a craniocaudal orientation medially
      and a horizontal anteroposterior orientation laterally. These findings suggest
      that the septa guide early local cancer extension parallel to their own
      arrangement, acting as barriers that cannot be easily crossed. Correspondingly,
      cranial and horizontal-lateral cancer spread along the ALSAC has been reported in
      the clinical literature.

PMID- 9561863
TI  - Dynamic behavior of the Provox and Staffieri prostheses for voice rehabilitation
      following total laryngectomy.
AB  - The present study evaluated the differences in aerodynamic behavior between the
      1990 Provox and 1986 Staffieri voice prostheses for total laryngectomy patients.
      Both prostheses were submitted to in vitro laboratory testing to assess their
      aerodynamic behavior under different conditions of air flow through the valve and
      tracheal side pressure. In addition, six patients using the Provox and another
      six using the Staffieri prostheses were submitted to a dynamic study of
      phonation. This latter study evaluated the intratracheal pressure corresponding
      to the different intensities at which the vowel sound /a/ was pronounced. In
      vitro measurements revealed significant differences between the two prostheses,
      with the best results achieved with Provox. In contrast, the in vivo measurements
      did not reveal any significant differences between the two groups of patients in
      the 50-79 dBSPL range, although there was some difference at intensities equal to
      or greater than 80 dBSPL. Again, in this latter case the best results were
      achieved with the Provox. However, the ideal prosthesis has yet to be found. In
      some patients, the so-called low-resistance prostheses fail to maintain their
      aerodynamic performances, most likely because anatomic resistors interfere with
      the effort (i.e., pressure) required to produce a voice. At present the choice of
      prosthesis is best determined on an individual patient-to-patient basis.

PMID- 9561864
TI  - A comparison of spiral and conventional computerized tomography methods in
      diagnosing various laryngeal lesions.
AB  - Although endoscopic procedures with tissue biopsy are the mainstay in the
      evaluation of laryngeal lesions, radiological imaging studies remain important.
      Computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound
      (US) are the most reliable methods, especially for deep laryngeal compartments,
      cartilage, extralaryngeal structures and neck nodes. However, the larynx is a
      difficult organ for radiological imaging because respiration and swallowing can
      cause several artifacts and distort image. In this report we studied the role of
      a spiral CT technique and compared this with conventional CT in 32 patients. We
      used the Hitachi W950SRBT machine and took both conventional and spiral sections
      of the larynx and neck in all 32 patients. The scans were taken with a 5-mm table
      motion and 5-mm section thickness in both studies. In the spiral technique the
      raw data acquired were used retrospectively for 2-mm and 5-mm reconstructions.
      Anatomic details, motion artifacts and vascular enhancements were compared by a
      scoring system. The mean values were then analyzed statistically by the paired t
      test. The average examination time was 3 min 18 s for conventional CT and 28 s
      for spiral CT. Anatomic detail scores were better in the 2-mm section spiral CT
      studies compared to 5-mm section spiral and conventional CT groups. Motion
      artifact scores were better in the 2-mm and 5-mm spiral CT groups compared to the
      5-mm conventional CT group. Vascular enhancement scores were better in the spiral
      CT group. Overall, the thinner (2-mm) sections of the spiral CT studies further
      improved image quality regarding both anatomic details and motion artifacts.
      Scanning time for spiral CT was very short, motion artifacts were less, and
      vascular enhancement and anatomic details were better. Volumetric data could also
      be reconstructed for thinner sections in all planes retrospectively for further
      evaluation. Our findings showed that spiral CT was a better method than
      conventional CT for evaluating laryngeal lesions.

PMID- 9561865
TI  - Analysis of tumor recurrence following anterior skull base surgery.
AB  - In order to elucidate the predictive factors for tumor recurrence following skull
      base surgery and the significance of salvage surgery in cases of recurrence, we
      retrospectively surveyed the incidence, site, and time of local recurrences in 20
      patients who underwent either anterior or anterolateral skull base surgery for
      malignant tumors invading the anterior cranial fossa between 1989 and 1995 at the
      University of Tokyo Hospital. Nineteen patients underwent total resections of
      malignancies, with recurrences and/or metastases occurring in 13. Local
      recurrences occurred at the skull base in 5 patients (group A), outside the skull
      base in 4 patients (group B), and in both locations in 2 patients (group C). The
      mean time interval between surgery and recurrence was 29 months in group A, and
      4.2 months in groups B and C. The local recurrence-free rates were 51% at 1 year
      and 34% at 5 years. Both brain and/or dural invasion and a microscopic positive
      surgical margin were proven to be predictive factors for tumor recurrences. The 3
      year local recurrence-free rate was 20% in patients with dural invasions and 83%
      in those without. The incidence of recurrence-free patients was 79% in cases with
      negative margins, with no patient being recurrence-free in positive cases. All
      recurrences found more than 6 months after the initial surgery resulted in
      patients being salvaged successfully by a second operation.

PMID- 9561866
TI  - A comparison of procaine penicillin with sulbactam-ampicillin in the treatment of
      peritonsillar abscesses.
AB  - The clinical efficacy of procaine penicillin and sulbactam-ampicillin was
      compared in patients with peritonsillar abscesses after peroral abscess drainage.
      Forty-two patients were randomly assigned to receive either procaine penicillin
      or sulbactam-ampicillin intramuscularly on an outpatient basis. The mean time
      required for clinical symptoms (throat pain, dysphagia and fever) to resolve was
      compared. No statistically significant difference was found between the clinical
      recoveries of patients using either antibiotic (P > 0.05). The authors conclude
      that intramuscular procaine penicillin can be safely prescribed on an outpatient
      basis to most patients with peritonsillar abscess after incision and drainage. In
      contrast, a broader spectrum and more expensive antibiotic, such as sulbactam
      ampicillin, should be reserved for non-responders.

PMID- 9561867
TI  - Delayed recovery of patients with Bell's palsy complicated by non-insulin
      dependent diabetes mellitus and hypertension.

PMID- 9561868
TI  - AIDS deaths are falling sharply.

PMID- 9561869
TI  - How relationships of U.S. men affect contraceptive use and efforts to prevent
      sexually transmitted diseases.
AB  - CONTEXT: Comparatively little is known about how U.S. adult men's attitudes and
      characteristics influence their decision to use contraceptives to prevent
      pregnancy and to take actions to protect themselves from infection with sexually
      transmitted diseases (STDs). METHODS: Attitudinal and background data on 1,595
      men from the 1991 and 1993 waves of the National Survey of Men (NSM) were used,
      through logistic regression techniques, to predict the likelihood of current
      contraceptive use to prevent pregnancy and recent efforts to avoid STD infection
      among men in three types of sexual relationship--marriage, cohabitation and
      dating. RESULTS: At the 1993 interview, 58% of men were using contraceptives to
      prevent pregnancy and 22% had recently taken actions to protect themselves from
      STDs. Men's concern about how easy a method was to use reduced the likelihood of
      STD protection, but had no influence on contraceptive use to prevent pregnancy;
      however, concerns about a method's risks to the female partner increased the
      likelihood of both outcomes. Couples in which the man expected his partner to
      take primary responsibility for contraception were 40% as likely to be protecting
      themselves against STDs as were couples in which the man believed he shared or
      had greater responsibility. Married men were the least likely to be protecting
      themselves against STDs, whereas men who were dating were the most likely to do
      so. CONCLUSIONS: Men's attitudes and characteristics were important predictors of
      contraceptive use to prevent pregnancy and of efforts to protect against STDs,
      even after controls for the female partner's characteristics were entered in the
      analysis. The findings emphasize the need to include men in interventions aimed
      at reducing unintended pregnancy and STD transmission.

PMID- 9561870
TI  - A profile of the adolescent male family planning client.
AB  - CONTEXT: Family planning programs and policies increasingly focus on the male
      partner's roles and responsibilities in contraceptive decision-making and use. To
      effectively tailor services for males, policymakers and providers must refine
      their understanding of men's psychosocial and reproductive health needs. METHODS:
      Using self-administered questionnaires, 1,540 sexually active males aged 19 and
      younger who attended family planning clinics in California provided information
      about their sexual behavior, contraceptive use, pregnancy and parenting history,
      and psychosocial characteristics. Logistic regression was used to examine factors
      that contributed to effective contraceptive use. RESULTS: Although 73% of
      participants reported having used a birth control method at first intercourse,
      only 59% said that they or their partner had used an effective method at last
      intercourse, and 35% had used no method. If the client was uncomfortable with his
      method, the odds that he had used an effective method at last intercourse were
      reduced (odds ratio, 0.4). The likelihood of use at last intercourse was
      increased among males who agreed with their partner about their method and those
      who had never impregnated a partner (1.4 and 1.9, respectively). CONCLUSIONS: To
      adequately serve young males, clinics must take into account their sexual and
      contraceptive histories. But screening should go beyond traditional family
      planning techniques to discuss how to improve communication with partners and
      other lifestyle issues that may interfere with consistent use.

PMID- 9561871
TI  - Impact of a high school condom availability program on sexual attitudes and
      behaviors.
AB  - CONTEXT: While making condoms available in high schools has provoked much debate,
      evidence on the actual effects of such programs on students' attitudes and
      behavior is sparse. METHODS: Prior to implementation of a condom availability
      program in a Los Angeles County high school, 1,945 students in grades 9-12 (98%
      of eligible students) completed a self-administered anonymous survey on their
      sexual behavior and on related knowledge and attitudes; one year later, 1,110
      students (59% of eligible students) completed a follow-up survey. RESULTS: There
      was no significant change over time in the percentage of males or females who had
      ever had vaginal intercourse or who had had vaginal intercourse during the year
      prior to the survey. The percentage of males who reported using condoms every
      time they engaged in vaginal intercourse during the past year increased
      significantly, from 37% to 50%, and the percentage of males who reported condom
      use at recently initiated first vaginal intercourse increased from 65% to 80%. On
      the other hand, female respondents showed no significant change in their condom
      use. The self-reported likelihood of using a condom for vaginal intercourse
      during the following year did not change significantly for students who had had
      vaginal intercourse, but it increased dramatically for those who, had never had
      vaginal intercourse. The students' attitudes toward sex and condom use either
      remained the same between surveys or changed in a direction favoring less sexual
      behavior and greater risk prevention. CONCLUSIONS: The condom availability
      program appears not to have produced an increase in sexual activity among high
      school students, and it appears to have led to improved condom use among males.
      The apparent strong effect on students' intention to use condoms and on males'
      use at first vaginal intercourse suggests that such programs may have a
      particular impact on the least sexually experienced adolescents.

PMID- 9561872
TI  - Breakage and acceptability of a polyurethane condom: a randomized, controlled
      study.
AB  - CONTEXT: Although the first commercial polyurethane condom was approved for use
      several years ago, no U.S. clinical trial has compared its performance to that of
      the latex condom. METHODS: In a masked crossover study, 360 couples were
      randomized to use three polyurethane condoms and three latex condoms. After each
      use, couples recorded condom breaks, condom slips and other aspects of
      performance. At completion of the study, couples compared the sensitivity, ease
      of use, fit and lubrication of the two types of condoms. RESULTS: The clinical
      breakage rate of the polyurethane condom was 7.2%, compared with 1.1% for the
      latex condom (relative risk of 6.6, 95% confidence interval of 3.5-12.3). The
      complete slippage rate (combining incidents during intercourse and withdrawal) of
      the polyurethane condom was 3.6%, compared with 0.6% for the latex condom
      (relative risk of 6.0, 95% confidence interval of 2.6-14.2). Most male users
      preferred the sensitivity provided by the polyurethane condom to that of the
      latex condom. CONCLUSIONS: The clinical breakage rate of the polyurethane condom
      is significantly higher than that of the latex condom. However, nearly half of
      the users preferred the polyurethane condom, which provides an option for couples
      who have rejected conventional condoms or who cannot use latex products.

PMID- 9561873
TI  - Predicting maternal behaviors during pregnancy: does intention status matter?
AB  - CONTEXT: Women's behavior during pregnancy, which can affect the health of their
      infant, may be influenced by their attitude toward the pregnancy. METHODS:
      Multivariate analyses of data from the 1988 National Maternal and Infant Health
      Survey and the 1988 National Survey of Family Growth were conducted to
      investigate whether women with unplanned births differ from other women in their
      pregnancy behavior, independent of their social and demographic characteristics.
      RESULTS: Women with intended conceptions are more likely than similar women with
      unintended pregnancies to recognize early signs of pregnancy and to seek out
      early prenatal care, and somewhat more likely to quit smoking, but they are not
      more likely than women with comparable social and demographic characteristics to
      adhere to a recommended schedule of prenatal visits once they begin care, to
      reduce alcohol intake, or to follow their clinician's advice about taking
      vitamins and gaining weight. Social and demographic differences in these
      behaviors are largely unaffected by planning status, indicating that these
      differences are independently related to pregnancy behaviors. CONCLUSIONS: Both
      the intendedness of a pregnancy and the mother's social and demographic
      characteristics are important predictors of pregnancy-related behavior.

PMID- 9561874
TI  - Compliance, counseling and satisfaction with oral contraceptives: a prospective
      evaluation.
AB  - CONTEXT: Oral contraceptive users' risk of accidental pregnancy may be higher
      than it should be, because of inconsistent pill-taking. However, few reliable
      data are available on pill users' everyday experiences with their method,
      especially characteristics that may affect consistency of use. METHODS: Two
      months after initiating or resuming oral contraceptive use, a nationwide sample
      of 943 women completed questionnaires examining their compliance with
      instructions for proper use, the quality of their interactions with their
      provider, their satisfaction with the method, and the frequency and costs of
      visits or calls to their providers because of pill-related side effects.
      Regression analyses were used to determine the factors associated with compliance
      difficulties and method dissatisfaction. RESULTS: In all, 47% of users missed one
      or more pills per cycle, and 22% missed two or more. Women who lacked an
      established pill-taking routine, who did not read and understand all of the
      informational material accompanying the pill package, or who experienced spotting
      or heavy bleeding had increased odds of missing two or more pills per cycle.
      Method satisfaction was most likely among women who were aware of the pill's
      noncontraceptive benefits, were satisfied with their relationship with their
      provider, had used the pill in the past and experienced few side effects. Some
      22% of users called their provider at least once about pill-related side effects,
      and 9% made at least one visit for this reason; these women spent $25 and $62,
      respectively, to treat side effects. CONCLUSIONS: Improving pill use is a shared
      responsibility of the provider, the patient and, to a lesser degree, pill
      manufacturers. Awareness of potential difficulties such as inadequate counseling
      is a key step in helping women use oral contraceptives effectively.

PMID- 9561875
TI  - Partner-specific sexual behaviors among persons with both main and other
      partners.
AB  - CONTEXT: If men and women engage in different sexual behavior with main partners
      than with other types of partners, then programs aimed at preventing the spread
      of sexually transmitted diseases (STDs) may need to address individuals'
      differential risk with each partner type. METHODS: Relationship characteristics,
      partner risk behaviors and sexual behaviors are examined among 123 male and 106
      female STD clinic patients who had both main and other partners. Individual-level
      comparisons are made for two types of partner pairs: main vs. other frequent
      (side) partners and main vs. casual partners. RESULTS: Among men and women with
      both main and side partners, the proportion who had known only their main partner
      for at least a year (48% of men and 41% of women) was significantly higher than
      the proportion who had known only their side partner for that long (2% and 9%,
      respectively); no other variable differed significantly by partner type. Among
      those with main and casual partners, both men and women were more likely to use
      alcohol or drugs before or during sex with main partners only (15%) than with
      casual partners only (1-3%). Women with main and casual partners were more likely
      to have oral sex only with main partners than only with casual partners (37% vs.
      3%), and were more likely to use condoms only with casual partners than only with
      main partners (33% vs. 4%). CONCLUSIONS: Providers need to ask individuals about
      their sexual behaviors with different partner types, and should tailor prevention
      messages to an individual's risks and reproductive intentions with each partner.

PMID- 9561876
TI  - Myocardial viability: known and unknown.
AB  - The assessment of myocardial viability has gained a lot of attention over the
      past few years. Various imaging techniques, mainly nuclear and echocardiographic
      approaches, have been developed for this purpose. From the existing data, it has
      become clear that the presence of dysfunctional yet viable myocardium can predict
      improvement of regional and global left ventricular (LV) function after
      revascularization. This issue is most relevant in patients with severely
      depressed LV function, since in these patients revascularization carries a high
      (peri-)procedural risk on the one hand, but may substantially improve LV function
      in some patients. Besides the improvement of resting LV function after
      revascularization, other end-points may also be clinically relevant, including
      the response during stress, improvement of exercise capacity, the quality of life
      and the prevention of LV remodeling. These issues have not been studied
      extensively thusfar. Finally, several retrospective studies have shown the
      prognostic value of viability assessment; patients with viable but jeopardized
      myocardium were significantly more prone to experience cardiac events than
      patients with viability who underwent revascularization. The different aspects of
      viability assessment (including pathophysiology, available techniques, current
      implications and unresolved issues) will be addressed in this manuscript.

PMID- 9561877
TI  - Short-term hemodynamic effects of DDD pacing from ventricular apex, right
      ventricular outflow tract and proximal septum.
AB  - Recently, short-term hemodynamic benefits of right ventricular outflow tract
      (RVOT) or proximal septum (His bundle area) pacing have been reported in
      comparison with traditional apical stimulation in preliminary investigations. The
      purpose of the present study was to compare the hemodynamics obtained during DDD
      pacing from ventricular apex, RVOT and proximal septum in patients with normal
      left ventricular function. A simultaneous hemodynamic and Doppler
      echocardiographic study was performed in 21 patients (age 67 +/- 7 years) with
      sick-sinus syndrome (8 pts) or 2nd-3rd degree atrioventricular (AV) block (13
      pts). The three stimulation sites were randomized and pacing was applied at an
      identical rate (84 +/- 5 beats/min) and at a constant AV delay (150 ms).
      Electrocardiographic, hemodynamic and Doppler-echocardiographic investigations
      were performed during stimulation from each site. The QRS duration did not show
      significant differences during DDD pacing from ventricular apex, RVOT and
      proximal septum. The hemodynamic measurements (systemic pressures, mean pulmonary
      wedge pressure, pulmonary pressures, right ventricular end-diastolic pressure,
      mean right atrial pressure, cardiac index, systemic vascular resistance and
      arteriovenous O2 difference) did not show significant differences during pacing
      from the three sites. Moreover, no significant differences were observed for the
      Doppler-echocardiographic measurements of systolic function (aortic stroke
      distance, left ventricular ejection fraction) and diastolic function
      (isovolumetric relaxion time, mitral E/A ratio, deceleration rate of the E wave).
      The results suggest that in patients with normal left ventricular function DDD
      pacing from RVOT or proximal septum does not improve cardiac function with regard
      to apical pacing.

PMID- 9561878
TI  - The shape of enzymatic curves during acute myocardial infarction: relationship to
      the progression of necrosis and implications for thrombolysis.
AB  - BACKGROUND: During acute myocardial infarction, the ascending branch of creatine
      kinase curves has a sigmoidal course whose inflection point marks the maximum
      rate of enzymatic increase in serum. This study was performed to assess the
      relationship between these morphologic characteristics of creatine kinase curves
      and the progression of myocardial necrosis. METHODS AND RESULTS: In isolated rat
      hearts exposed to different degrees of ischemia (coronary flow of 0.6 or 0.2
      ml/g/min), the total quantity of creatine kinase released in the effluent had a
      sigmoidal course similar to the ascending branch of the curves from patients with
      acute myocardial infarction. Other rat hearts were frozen (which causes maximum
      damage to cell structures), thawed and then perfused. The resulting enzymatic
      curves had a downward concave ascending trend, similar to the portion beyond the
      inflection point of sigmoidal curves (the rate of creatine kinase release was
      maximum at the onset of perfusion and then decreased progressively). Finally, in
      some experiments ischemic rat hearts were further damaged by the perfusion, at
      different times, with highly concentrated catecholamines and without oxygen and
      substrates. This damaging perfusate was able to increase the rate of creatine
      kinase release (p = 0.0001) only when it was started before the inflection point
      of enzymatic curves. In 25 creatine kinase curves from patients with acute
      myocardial infarction (19 men and 6 women, age range 42 to 68 years), who were
      not treated with thrombolysis, the time of inflection varied from 1 to 12 hours
      from the onset of symptoms, with a maximum frequency between the 7th and the 8th
      hour. CONCLUSIONS: Based on these data, a biological model with 3 compartments
      has been suggested to explain the shape of creatine kinase curves, according to
      which the inflection point would occur after the completion of myocardial
      necrosis. The variability of the time of inflection might account for the cases
      of beneficial late thrombolysis reported in literature.

PMID- 9561879
TI  - [Improvement of postinfarct left myocardial contractile function after
      administration of diltiazem].
AB  - BACKGROUND: The impairment of intracellular calcium homeostasis is an important
      biochemical alteration in stunned and hibernating myocardium. These different
      forms of viable myocardium frequently occur after myocardial infarction and their
      recognition may modify the therapeutic program and prognosis. Experimental
      studies and experiences on male subjects have demonstrated that calcium-channel
      blockers exert a protective action on myocardial reperfusion injury and reduce
      infarct size. OBJECTIVES: The aim of the present study was to evaluate the
      efficacy of i.v. diltiazem (i.e. a calcium-channel blocker with negative
      inotropic effect) in enhancing the contractility of viable akinetic myocardium in
      patients after myocardial infarction. METHODS: Sixty patients (52 males and 8
      females, age 57 +/- 10 years) with the first acute myocardial infarction were
      evaluated with dobutamine-echocardiography 9 +/- 2 days after admission and on
      the following day with diltiazem-echocardiography. Diltiazem was administered
      i.v. using repeated boluses of 0.25 mg/kg up to the maximum dose of 1 mg/kg.
      Before and during the infusion, left ventricular regional function was scored and
      the Wall Motion Score Index (WMSI) was calculated; ECG and arterial blood
      pressure were also monitored. Results were compared with low-dose dobutamine
      echocardiography. In a subset of 13 patients who underwent myocardial
      revascularization (7 coronary artery by-pass graftings and 6 percutaneous
      transluminal angioplasties), post-procedure echocardiograms were performed to
      evaluate whether regional left ventricular function had improved. RESULTS: Low
      dose dobutamine and diltiazem enhanced regional left ventricular contractility in
      28 and 31 patients, respectively; both tests were positive in 26 cases.
      Conversely, dobutamine-test was negative in 32 patients and diltiazem in 29, with
      concordance in 27. A good correlation was found between diltiazem and dobutamine
      WMSI at the basal evaluation (r = 0.91; p < 0.000) as well as during the
      pharmacological test (r = 0.86; p < 0.000). In patients who underwent myocardial
      revascularization, the same good correlation was found between diltiazem-WMSI and
      WMSI evaluated after the procedure (r = 0.91; p < 0.000). CONCLUSIONS: Acute i.v.
      administration of diltiazem about ten days after myocardial infarction may
      enhance the contractility of viable akinetic ventricular wall segments, as
      evaluated with echocardiography. The results of this study may have some
      physiopathological and therapeutical implications that could lead to
      reconsidering the use of calcium-channel blockers, particularly diltiazem, in
      selected patients after myocardial infarction.

PMID- 9561880
TI  - [Family and friends who smoke: influence on adolescents].
AB  - BACKGROUND: Smoking is the leading preventable cause of death. Most cigarette
      smokers take up the habit during adolescence. The purpose of this study was to
      assess the prevalence of cigarette smoking behavior among the students of a
      metropolitan high school as compared to those attending a non-metropolitan high
      school, examining age, sex and demographic and socioeconomic differences, as well
      as the influence of smoking models (family members and friends) on smoking
      behavior among adolescents. METHODS AND RESULTS: Nine hundred seventy-eight
      students (544 males, 434 females; mean age 15.8 +/- 1.5 years) attending a high
      school in the city of Naples and 467 students (235 males, 232 females; mean age
      16 +/- 1.5 years) from a high school of Capua, a small town 40 kilometers away
      from Naples, filled out an extensive questionnaire on smoking. The prevalence of
      smokers was 24.2% (males 21.8%, females 28.2%; p = 0.02) in Naples and 23.8% in
      Capua (males 29.8%, females 19.2%; p < 0.001) and was related to age (p < 0.001)
      both in Naples and in Capua. In Naples, smoking behavior among male students was
      associated with smoking by sibling (p = 0.00005), whereas an association with
      father (p = 0.0003), mother (p = 0.00005), parental (p = 0.0002) and sibling (p =
      0.00002) smoking was observed among females. In Capua, an association was evident
      only between smoking in female students and sibling smoking habits (p = 0.02). In
      both Naples and Capua, smoking status of the students was related to smoking
      habits of best friends of the same sex, best friends of the opposite sex and
      friends. Multivariate analysis showed an independent relationship in Naples
      between adolescent smoking behavior and smoking status of siblings (p = 0.01),
      best friends of the same sex (p < 0.001) and best friends of the opposite sex (p
      < 0.001). In males, smoking behavior was associated with the smoking behavior of
      best friends of the same (p < 0.001) and of the opposite sex (p = 0.01), whereas
      in females, it was linked with the smoking behavior of siblings (p = 0.05),
      mother (p < 0.05) and best friends of the same sex (p < 0.001). In Capua, student
      smoking was related to smoking among friends (p < 0.001) and this held true for
      both males (p = 0.05) and females (p < 0.0001). CONCLUSIONS: The prevalence of
      smoking habits among teenagers is similar in two distinct populations of high
      school students from a city and from a small town. Smoking showed a higher
      prevalence among females in the city and among males in the small town. It
      increases with age and is related to peer and family smoking models. This study
      has identified several variables associated with smoking status among
      adolescents. We thus feel that these findings may contribute to a better
      understanding of smoking behavior among teenagers and may have prevention
      implications.

PMID- 9561881
TI  - [Non-cardiac transcatheter intervention: operative possibilities in a
      hemodynamics laboratory].
AB  - INTRODUCTION: New possibilities for transcatheter treatment of the cardiovascular
      system are guaranteed with the improvement of materials and the availability of
      new devices. Nevertheless, a rationalization of the potential activity in this
      sector seems to be necessary, and it could arise through the presence of
      Catheterization Laboratories "open" to diagnostic procedures and therapy that are
      not confined to the coronary system. This clinical study reports the experiences
      and results of our work in this field. MATERIALS AND METHODS: During the period
      from May 1995 to May 1997, our laboratory performed 205 diagnostic procedures
      that did not involve the coronary system. Based on this diagnostic work, there
      emerged 91 cases with an indication for transcatheter intervention, which was
      subsequently performed at our laboratory. There were 68 peripheral angioplasty
      procedures on the iliofemoral axis, 2 angioplasties of the subclavian artery, 8
      of the renal artery, 2 procedures involving the treatment of A-V fistulas, one
      case of femoral pseudoaneurysm treatment and 10 cases of transcutaneous
      pericardiotomy performed with a balloon catheter. All the procedures were
      performed by our laboratory staff using materials that are normally at our
      disposal. RESULTS: Successful results were obtained in 65 out of the 68
      peripheral angioplasty procedures and in all of the 8 renal and 2 subclavian
      angioplasties. The positioning of the endoprosthesis for the closure of the A/V
      fistula was effective in one of the two cases. The transcatheter treatment of the
      femoral pseudoaneurysm was successful. In all cases where a pericardiotomy was
      performed with a balloon catheter, there was no reoccurrence of cardiac tamponade
      during the follow-up period. No complications were noted as a result of any of
      the procedures. CONCLUSIONS: Our experience documents how it is possible to
      increase the diagnostic and therapeutic options in a Catheterization Laboratory.
      However, willingness on the part of the staff to update their skills continually
      and collaborate with other specialists is necessary in order to maintain optimal
      operative standards.

PMID- 9561883
TI  - [Context and background after infarction. GISSI nursing].
AB  - INTRODUCTION: While the clinical course of myocardial infarction (AMI) from
      symptoms to outcome has been investigated in great detail, only a few data are
      available from the patients' side on their subjective feelings, their experience
      and their awareness of risk before the occurrence of AMI. METHODS: A sample
      population of 3863 AMI patients, randomized for the GISSI-3 study, was
      interviewed by nurses an average of four days after the AMI. The questions
      explored the activities performed at the time the AMI occurred, the patients'
      perceptions and the preventive practices that were adopted. RESULTS: AMI occurs
      in "normal" life situations: only 10.3% patients reported heavy exertion
      immediately before the onset of AMI and 5.6% reported emotional involvement as a
      possible acute trigger. A large majority of patients would associate the AMI with
      something wrong or unusual occurring before the event. On average, > 60% patients
      associated the AMI with cardiac symptoms (chest pain, shortness of breath) or
      with psychological symptoms, such as anxiety; an important minority (30%)
      associated it with joint pain or a fever, suggesting inflammation as a possible
      trigger event. Preventive practices were declared by 25% of patients, but the
      number drops to 6% if at-risk patients (those with a history of AMI or angina)
      are excluded. Diet and drugs are the most widely adopted practices. Male sex and
      a history of AMI are linked with a more widespread use of preventive practices.
      Younger patients and patients with a higher education modified their lifestyle
      (exercise, smoke) to a greater extent, while there are no major differences
      between patients with or without a history of hypertension and angina.
      CONCLUSIONS: Large-scale use of preventive practices is very unlikely, and this
      is true not only for the general population, but also for AMI "at-risk" groups.
      These patients (elderly, less-educated people) should be the target of specific
      educational interventions aimed at increasing the awareness of risk and promoting
      safer and more health-oriented lifestyles.

PMID- 9561882
TI  - [Coronary angiography in two defined populations: Padua and Citadella].
AB  - BACKGROUND: Coronary angiography is an invasive procedure that is relatively
      expensive and that requires an appropriate indication. METHODS: Utilization rate
      and the appropriateness of the use of the coronary angiography have been compared
      in two defined populations, namely residents from the city of Padua (group A),
      and subjects from the local health unit of Cittadella (group B), who underwent
      coronary angiography between June 1, 1992 and May 31, 1993. Appropriateness was
      evaluated both by comparison with the AHA/ACC guidelines and by observation of
      the outcome following diagnosis one year after the coronary angiogram was
      performed. RESULTS: One hundred and seventy-one patients in group A and 100
      patients in group B underwent coronary angiography: both groups had similar age
      and sex distribution. Utilization rate was 8 per 10,000 inhabitants in group A,
      and 10 per 10,000 inhabitants in group B. Appropriate coronary angiography,
      evaluated by comparison with the AHA/ACC guidelines, was 69.9% in group A and 68%
      in group B. Coronary angiogram showed at least one stenosis > or = 50% in 133
      patients from group A and in 66 patients from group B. These patients were
      followed up for at least 12 months. Of 13 deaths, 12 occurred as fatal cardiac
      events, while of the 147 surviving patients who had complete follow-up data, 114
      (77%) improved. The outcome was measured through symptoms and stress test. In
      addition, subjective improvement was measured in group A using the "Nottingham
      Health Profile". CONCLUSIONS: Criteria of appropriateness for an invasive
      diagnostic procedure such as coronary angiography, which is a determinant "entry
      point" for revascularization procedures, is based on common clinical knowledge
      that may be evolving with time. Based on these data, it seems that the current
      guidelines could be modified, especially for indications within the setting of
      myocardial infarction.

PMID- 9561884
TI  - Coexistence of vessel enlargement and paradoxical constriction in a diseased left
      anterior descending artery: an in vivo assessment using a new system for
      quantitative analysis of intracoronary ultrasound.
AB  - Previous studies based on conventional two-dimensional intravascular ultrasound
      revealed that coronary arteries can undergo either vessel enlargement and
      paradoxical constriction in response to plaque growth. We report a case in which
      the occurrence of vessel enlargement and paradoxical constriction was documented
      in the same coronary artery (left anterior descending). A multiple cross-section
      analysis was performed, using a novel 3-D system of reconstruction of IVUS
      images, which provides a large number of cross-sections within the reconstructed
      segments.

PMID- 9561885
TI  - An uncommon false aneurysm of the left ventricle.
AB  - An 83-year-old woman with previous closed transventricular commissurotomy was
      admitted for congestive heart failure. Echocardiogram and angiography
      demonstrated a mitral restenosis and a large-mouthed false aneurysm of the left
      ventricle.

PMID- 9561886
TI  - Familial atrial septal defect with atrioventricular conduction defects.
AB  - Atrial septal defect of the ostium secundum type is almost always sporadic, with
      multifactorial inheritance. We report a case of a family in which atrial septal
      defects of the ostium secundum type with atrioventricular conduction defects were
      observed in four generations: five proven cases and two probable cases. Ten
      families have been reported as showing atrial septal defect of the ostium
      secundum type and atrioventricular conduction defects with dominant inheritance.
      Moreover, in our family the transmission model can also confirm autosomal
      dominant inheritance. We believe that cardiologists should take a familial
      approach to atrial septal defect of the ostium secundum type for both research
      and genetic counseling purposes. In a patient with ASD II, the AV conduction
      defects should prompt a detailed family history and clinical evaluation of first
      degree relatives.

PMID- 9561887
TI  - [Clinicopathological conference: sudden coronary death in a 32-year old man].
AB  - A 32-year-old man without risk factors for coronary artery disease but moderate
      cigarette smoking died suddenly 5 years after a cardiological check-up for chest
      pain on effort. Autopsy investigation ruled out extracardiac causes of death and
      pointed to a multivessel coronary artery disease with organized and recanalized
      occlusive thrombosis, sometimes superimposed to smooth muscle cells
      proliferation, in the absence of peripheral vascular disease. Thromboangiitis
      obliterans of the coronary arteries or accelerated atherosclerosis complicated by
      thrombosis due to endothelial erosion are debated as possible etiopathogenetic
      mechanisms. The case is still open for achieving a final diagnosis.

PMID- 9561888
TI  - [Acute myocardial infarction following administration of a synthetic analog of
      prostaglandin E2 in a subject with an intramural course of the anterior
      intraventricular artery].
AB  - We report a case of acute myocardial infarction which occurred after
      administration of a synthetic analog of prostaglandin E2 (PGE2) for the voluntary
      interruption of pregnancy in a 31-year-old woman who had previously been
      asymptomatic, with myocardial bridging of the left anterior descending artery.
      The pathogenesis of the severe ischemia causing myocardial infarction and left
      ventricle aneurysm is quite unclear. The temporal connection is highly indicative
      of a causal relationship between the pharmacological effects of a synthetic PGE2
      analog and coronary spasm responsible for severe ischemia. The hypothesis of
      endothelial dysfunction proximal to the intramyocardial artery tract and
      paradoxical vasoconstriction with platelet activation should be taken into
      consideration. A possible additional effect seems to be a horizontal coronary
      steal produced by the administration of PGE2 in the myocardium below the
      intramyocardial artery tract. It cannot be excluded that pharmacological doses of
      a synthetic analog of PGE2 may have inverted the vasoactive effects of the
      substance due to direct stimulation on the delivery of constrictive agonist
      factors.

PMID- 9561889
TI  - [Atrial fibrillation triggered by supraventricular tachycardia: an apparently
      idiopathic form that is treatable with radiofrequency].

PMID- 9561890
TI  - [Intramural aortic hematoma].
AB  - Aortic dissection is a medical and/or surgical emergency that is usually
      catastrophic if not diagnosed and treated promptly. Transesophageal Doppler
      echography provides an accurate method of diagnosing and evaluating dissection of
      aortic aneurysm. Due to the high resolution of transesophageal echocardiography,
      special subtypes of aortic dissection such as intramural hemorrhage can be
      diagnosed. The purpose of this paper is to report a case and review the
      anatomical, clinical and transesophageal echocardiography aspects of aortic
      dissection without intimal rupture (intramural hematoma).

PMID- 9561891
TI  - [Cardiomyopathy: definitions and classification].

PMID- 9561892
TI  - [Arterial hypertension guidelines: resolved and unresolved problems].

PMID- 9561893
TI  - Antenatal screening for Down's syndrome.

PMID- 9561894
TI  - Screening for ovarian cancer: a systematic review.

PMID- 9561895
TI  - Consensus development methods, and their use in clinical guideline development.

PMID- 9561896
TI  - Langerhans cell histiocytosis. Historical perspectives.

PMID- 9561897
TI  - Nosology and pathology of Langerhans cell histiocytosis.
AB  - The pathology of LCH is continuing to be defined and diagnostic features
      clarified as unprecedented research is done. Although the etiology of LCH remains
      unknown, new information on cytokines, viruses, immunologic dysfunction, cell
      surface antigen expression, and clonality in the disease are providing essential
      pieces of the puzzle.

PMID- 9561898
TI  - Clinical aspects of Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis remains an enigmatic disease with protean
      manifestations. It may be self-limited in some, whereas in others, even intensive
      treatment is unsuccessful. The outcome depends on whether vital organ function is
      compromised at diagnosis or shortly thereafter, in which case the prognosis is
      grave.

PMID- 9561899
TI  - Langerhans cell histiocytosis in adults.
AB  - Langerhans cell histiocytosis in the adult is rare, but it is important to
      recognize its occurrence, as it must be differentiated from lymphoma, myeloma,
      and a variety of skin conditions and endocrinopathies. It has been reported in
      patients up to the ninth decade of life, and occurs equally in men and women.
      Local disease has a good prognosis, but associated diseases--particularly
      malignancy--may be the cause of death in some adults. The optimal treatment is
      not known. Coordinated investigation of the epidemiology and therapy of this
      disease is needed.

PMID- 9561900
TI  - Langerhans cell histiocytosis of the skin.
AB  - Cutaneous involvement in Langerhans cell histiocytosis (LCH) occurs in 50% of
      cases and may be the presenting feature. It is, therefore, important to recognize
      the wide spectrum of clinical disease that this disorder may adopt in the skin.
      Cutaneous involvement is not necessarily a benign feature and many patients
      progress to multi-system disease. There are a number of treatments available for
      cutaneous LCH. The rationale is to start with the simplest treatment and progress
      to systemic or interventional therapy as needed.

PMID- 9561901
TI  - Central nervous system disease in Langerhans cell histiocytosis.
AB  - Central nervous system (CNS) disease in Langerhans cell histiocytosis (LCH) is a
      poorly understood complication of yet unknown frequency. By far the most common
      manifestation is in the hypothalamic-pituitary system with diabetes insipidus as
      the leading sign, followed by other endocrinopathies and hypothalamic
      dysfunction. However, essentially all other parts of the CNS may be involved. On
      the one hand, space-occupying histiocytic infiltrates may lead to size- and site
      depending symptoms, extending from adjacent bone lesions or arising from the
      meninges or choroid plexus. On the other hand, a progressive neurological
      deterioration can occur with mainly cerebellar-pontine symptoms. In this article,
      these clinical patterns are described in correlation with the morphology on MR
      imaging and histopathology. Further, the therapeutic strategies are reviewed
      critically, and guidelines for the management of patients with LCH-related CNS
      disease are presented.

PMID- 9561902
TI  - The role of radiology in the diagnosis and follow-up of Langerhans cell
      histiocytosis.
AB  - Diagnostic imaging plays a major role in the management of patients with
      Langerhans cell histiocytosis. Plain radiography depicts most lesions. Nuclear
      scintigraphy may detect additional areas of bone involvement, but its routine use
      is controversial. Ultrasonography may be used to evaluate the abdomen for
      evidence of solid organ involvement. CT and MR imaging are often of great value
      in clarifying and delineating findings seen on plain radiographs and other
      imaging modalities. Ultimately, the choice of imaging study depends on the
      patient's clinical presentation and the body part affected.

PMID- 9561903
TI  - Current therapy for Langerhans cell histiocytosis.
AB  - The changing concept of the pathogenesis of Langerhans cell histiocytosis over
      the past 50 years has been mirrored by evolving treatment regimens. The
      publications by the Histiocyte Society in the 1980s of diagnostic, clinical, and
      laboratory criteria allowed international collaboration in treatment trials.
      These, in turn, have allowed stratification of risk groups and the evolution of a
      salvage therapy protocol for the poorest risk patients. Experimental therapies
      now being evaluated may be the treatment strategies for the next decade.

PMID- 9561904
TI  - Controversies and new approaches to treatment of Langerhans cell histiocytosis.
AB  - There continues to be genuine ambivalence as to whether Langerhans cell
      histiocytosis (LCH) is a primary neoplastic or immuno-dysregulatory disorder.
      Treatment strategies have moved from one camp to the other depending upon the
      most current alleged successes or failures. This has been particularly true for
      patients who fall outside of the sphere where treatment is minimal or where known
      treatment approaches are clearly beneficial. However, there is growing evidence
      that LCH is both the result of clonal proliferation of Langerhans cells and the
      immunologic consequence of increased cellular activation. This new knowledge
      should be the basis for the development of new therapeutic approaches for
      patients with LCH and its complications.

PMID- 9561905
TI  - A framework for understanding and responding to the psychosocial needs of
      children with Langerhans cell histiocytosis and their families.
AB  - This article presents a five-point framework to help health-care providers
      understand and manage important psychosocial issues related to Langerhans cell
      histiocytosis (LCH). It entails frank and open discussions with patients and
      their families of how the disease can affect them individually and collectively.
      Each point is explained and then applied to two different cases. The framework is
      applicable to all chronic pediatric diseases, but is particularly relevant for
      rare conditions with unknown etiologies such as LCH.

PMID- 9561906
TI  - The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and
      other solid tumors. The LCH-Malignancy Study Group of the Histiocyte Society.
AB  - The frequency of Langerhans cell histiocytosis (LCH) and a malignant neoplasm
      occurring in the same individual appears to be greater than previously
      recognized. To define the occurrence and the pattern of these events, a Study
      Group of the Histiocyte Society initiated a registry of patients in whom this
      association occurred synchronously or asynchronously. Evaluation of 54 patients
      detected two patterns of associations between LCH and other disorders. First, it
      is possible that therapy of LCH promotes a secondary malignancy. Second, it is
      possible that a genetic predisposition, with or without the immunosuppression
      associated therapy for the malignancy, plays a role in the development and
      expression of disseminated LCH. Data collected by the LCH-Malignancy Study Group
      may provide insights into the etiology and pathophysiology of LCH.

PMID- 9561907
TI  - The epidemiology of Langerhans cell histiocytosis.
AB  - Little progress has been made in finding the causes of LCH. Epidemiologic studies
      are difficult because of the rarity of this disease. Although several
      associations have been demonstrated in case-control studies, particularly that
      with thyroid disease, no causal relationships have been documented. Additional
      case-control studies may uncover the to-date missing lead that may prove fruitful
      for epidemiologic investigation.

PMID- 9561908
TI  - Langerhans cell histiocytosis research. Past, present, and future.
AB  - This article reviews the various investigative events that led to the endorsement
      of the term Langerhans cell histiocytosis for the various clinicopathologic
      conditions previously called Hand-Schuller-Christian disease, Abt-Letterer-Siwe
      disease, eosinophilic granuloma of bone, and histiocytosis X. The different
      denominations reflect the changing conceptual approaches to the so-called
      reticuloendothelial system and the successive acquisition of new ultrastructural
      and immunocytochemical data.

PMID- 9561909
TI  - An update on clonality, cytokines, and viral etiology in Langerhans cell
      histiocytosis.
AB  - Many etiologies have been proposed for Langerhans cell histiocytosis (LCH).
      Recent scientific studies have clearly provided new insights into the etiology
      and pathogenesis of the disease. The possible role of viruses has not been
      completely negated, but no viral genomes have been consistently detected in LCH
      lesions. Other studies do not indicate that LCH arises from a primary defect in
      the immune system, although altered immune responses and immune dysfunction may
      play a role in the pathophysiology of the disease. Definitive results have been
      gained from molecular studies of clonality, however. These have definitively
      established that LCH is a clonal histiocytic disease rather than a reactive
      polyclonal disorder.

PMID- 9561910
TI  - Familial hemophagocytic lymphohistiocytosis. Primary hemophagocytic
      lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis represents a spectrum of pathogenetically
      different diseases including the rapidly fatal autosomal recessive disease of
      familial hemophagocytic lymphohistiocytosis (FHL). The onset is usually during
      the first years of life with fever, cytopenia, and hepatosplenomegaly. Neurologic
      symptoms may supervene. Similar symptoms may occur in the infection-(virus
      )associated or malignancy-associated hemophagocytic syndromes (IAHS/MAHS).
      Triggering infections can be found in all these diseases and do not allow for
      reliable differentiation. An international treatment protocol (HLH-94) has been
      developed for FHL, but immunomodulatory treatment may be justified in IAHS and
      MAHS as well, since they also have a high fatality rate.

PMID- 9561911
TI  - Infection- and malignancy-associated hemophagocytic syndromes. Secondary
      hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis represents a spectrum of pathogenetically
      different diseases in which a T-cell induced, uncontrolled activation of
      phagocytosing macrophages may lead to fever, organomegaly, and pancytopenia. The
      underlying immunologic disturbance can either be genetically transmitted, like in
      FHL, or acquired, as in IAHS or MAHS. Triggering infections can be found in all
      these diseases and do not allow a reliable differentiation. An international
      treatment protocol has been developed for FHL. IAHS and MAHS also have a high
      fatality rate, justifying immunomodulatory treatment if the disease is
      progressive.

PMID- 9561912
TI  - Malignant histiocytosis. Histologic, cytochemical, chromosomal, and molecular
      data with a nosologic discussion.
AB  - Although myelomonoblastic leukemia is thought to originate from a malignant
      transformation of the stem cell of the mononuclear phagocyte system, malignant
      histiocytosis (MH) is classically assumed to represent a malignant change of the
      terminal and fixed elements of this system. Indeed, MH is characterized by the
      proliferation of large, clear, pleomorphic, "histiocytic-like" HLADR and CD30+
      cells resulting in a nodal and extranodal disseminated neoplasm affecting
      preferentially and severely children and young adults. Although there is broad
      agreement on the clinicopathologic presentation of this condition, there is
      currently quite a controversy over the T-lymphoid or histiocytic origin of the
      proliferative cells that results in a nosologic discussion between the anaplastic
      large cell lymphoma (ALCL) advocates and the MH supporters. This article has
      dealt mainly with this nosologic discussion and with the contributions provided
      by the investigations performed on MH permanent cell lines. These in vitro
      studies have demonstrated that the proliferation is characterized by a unique
      chromosomal abnormality, the 5q35bp usually associated with a t(2;5)
      translocation generating a fusion gene NPM/ALK and the subsequent translation of
      p80 protein. Although it is known that no single chromosomal abnormality is
      strictly restricted to a cell lineage, this 5q35bp and associated translocations
      seem today to represent the hallmark for this condition. In view of these
      chromosomal aberrations, the CD30+ ALCLs represent a heterogeneous group because
      15% to 50% express the NPM/ALK fusion gene. In addition, these in vitro
      investigations have shown that 5q35bp proliferative cells are glass-adherent, can
      develop an immunodependent phagocytosis, and are able to reduce NBT and produce
      TNF-alpha. More significantly, they express constitutively the c-fms (the
      receptor of the macrophage growth factor) and, under TPA stimulation, are able to
      modulate the expression of this receptor and its ligand, as well as TNF-alpha and
      IL-1. None of these cell lines express CD3, but several express CD68 and CD71. In
      contrast, genomic investigations have shown the underlying existence of
      monoallelic and even biallelic gene rearrangements for TCR beta and IgJH. In view
      of these discrepancies between the genomic and phenotypic features of these
      cells, the histogenetic debate should remain open but must take into account
      these new chromosomal and molecular data.

PMID- 9561913
TI  - Malignant histiocytic disorders in children. Clinical and therapeutic approaches
      with a nosologic discussion.
AB  - Malignant histiocytic disorders, other than leukemias, are extremely rare in
      childhood. Despite unresolved nosologic and terminologic difficulties, they
      should be classified according to the lineage of the aberrant cells in a given
      tumor. There are no common and typical clinical presentations, nor are there
      established treatment modalities available. For the disseminated forms,
      aggressive systemic treatment modalities--similar if not identical to those used
      for large cell anaplastic lymphomas--appear to be the best treatment option. For
      the localized forms, which are primarily dendritic cell sarcomas, a more
      localized and individualized therapy is appropriate.

PMID- 9561914
TI  - Positive regulatory gamma delta T cells in contact sensitivity: augmented
      responses by in vivo treatment with anti-gamma delta monoclonal antibody, or anti
      V gamma 5 or V delta 4.
AB  - Contact sensitivity (CS) responses, induced by skin painting with reactive
      haptens like picryl chloride or oxazolone, are classical examples of in vivo
      immunity mediated by alpha beta T cells. Our previous studies showed that gamma
      delta T cells were required to assist the alpha beta CS-effector T cells in the
      successful adoptive cell transfer of CS responses. These spleen and lymph node
      derived gamma delta+ CS-assisting regulatory cells were CD3+, CD4-CD8+, non
      antigen-specific, and non-MHC-restricted, and preferentially expressed V gamma 5
      and V delta 4 variable regions. In the current study we show that systemic
      treatment of mice in vivo with anti-gamma delta mAb, produced a similar positive
      influence on CS responses in two different systems: i.e. active sensitization, or
      adoptive cell transfer. In addition to augmented CS responses produced by
      treatment with pan anti-gamma delta TCR mAb, anti-gamma delta-V region mAb were
      examined, and augmentation of CS also was produced by anti-V gamma 5 and anti-V
      delta 4 mAb, the V regions determined previously to be preferentially expressed
      on gamma delta CS-assisting cells. We speculate that the positive influence of
      anti-gamma delta mAb was not caused by quantitative changes in gamma delta T
      cells, because FACS studies demonstrated a lack of in vivo depletion of
      peripheral blood and lymphoid gamma delta T cells, and also no depletion of
      epidermal dendritic gamma delta T cells (DETC), in mice treated with anti-gamma
      delta TCR mAb. Instead, our data favor the hypothesis that CS-assisting gamma
      delta T cells can be activated in vivo by anti-gamma delta TCR mAb interacting
      with their gamma delta TCR, at least with the short term protocols we employed,
      resulting in augmentation of CS responses perhaps by releasing positively-acting
      factors, such as certain cytokines.

PMID- 9561916
TI  - A non-radioisotopic human natural killer cell assay using rhodamine-123
      fluorescent dye as labelling probe.
AB  - A non-radioisotopic method for assessment of human natural killer (NK) cell
      activity in peripheral blood mononuclear cells (PBMC) was established by
      labelling K562 erythroleukemia target cells with a fluorescent dye, rhodamine-123
      (Rh-123). The labelling and assay conditions were determined for minimizing
      spontaneous release (SR). In order to investigate whether NK activity assessed by
      measuring Rh-123 release agrees with the activity determined by a 51Cr release
      assay, the NK activity of PBMC was measured simultaneously by both assay methods.
      Statistical analysis demonstrates that NK activities determined by Rh-123 release
      correlate well with those measured by 51Cr release. The Rh-123 release assay
      under the conditions determined was found to be applicable to measurement of the
      enhanced NK activity resulting from pretreatment of effector leukocytes with
      interferon-alpha. It is concluded that the Rh-123 release assay with use of K-562
      labelled target cells is practical for the assessment of human NK activity in
      laboratories where use of radioisotopes is not permitted or undesirable.

PMID- 9561915
TI  - Relationship between HLA antigens and infectious agents in contributing towards
      the development of Graves' disease.
AB  - Graves' disease (GD) is an autoimmune thyroid disorder which is associated with
      the human leucocyte antigens HLA-DR3 and DQA1* O501 in Caucasians. We have
      explored the possibility that some patients with certain HLA specificities
      develop anti-HLA antibodies which are correlated with environmental factors that
      may contribute to the development of GD. We studied 40 GD patients and 157
      healthy individuals (controls). Serology was used to type HLA-A, -B, -Cw, and -DR
      antigens. The frequencies of these antigens in relation to lymphocytotoxic anti
      HLA-A-B-Cw-DR antibodies and two environmental factors (Yersinia enterocolitica
      and Coxsackie B virus) were determined. The frequencies of HLA-B15, -B21 and DR3
      antigens were increased, whereas HLA-DR5 antigen was decreased in GD patients. A
      significant association between HLA-DR3 antigen and lymphocytotoxic antibodies
      was observed, i.e., IgGs from GD patients were cytotoxic to HLA-DR3+ normal B
      cells. Following absorption with Yersinia enterocolitica or Coxsackie-B-virus,
      only Coxsackie-B virus completely inhibited the lymphocytotoxic reactions against
      HLA-DR3+ B cells. Besides confirming the association of HLA-DR3 with GD, this
      study also suggests the role of Coxsackie-reactive HLA-DR3 antibodies as
      contributing factors to the pathogenesis of the disease.

PMID- 9561918
TI  - Glycosylated extracellular domains of membrane immunoglobulin M contribute to its
      association with mb-1/B29 gene products and the B cell receptor complex.
AB  - It has recently become clear that the B cell antigen receptor, membrane
      immunoglobulin (mIg) is part of a complex composed of a number of different
      polypeptides. In a manner analogous to the T cell receptor, mIg has been found to
      be associated with several tyrosine kinases, and other proteins, which although
      not kinases themselves become targets of kinase activity upon binding of mIg to
      antigen. Thus the B cell receptor complex appears to be a structure whose
      function during signal transduction is to facilitate the interaction of tyrosine
      kinases with their proper substrates, and to coordinate the phosphorylation of
      these proteins with the binding of antigen to mIg. In an effort to understand the
      nature of the interactions which mediate the organization of the B cell receptor
      complex, we have explored binding of components of the complex including Ig-alpha
      and Ig-beta to IgM. Previous results have indicated that binding was mediated by
      transmembrane domains. Our results indicate that extracellular domains of IgM may
      also contribute to its association with Ig alpha and beta and other members of
      the B cell receptor complex.

PMID- 9561917
TI  - Release of the soluble interleukin-6 receptor from human T-cells.
AB  - The soluble Interleukin-6 receptor (sIL-6R) is capable of conferring the
      Interleukin-6 (IL-6) signal onto cells lacking the gp80 ligand binding protein.
      Here we investigate the release of sIL-6R from T-cells. After 2 h stimulation
      with PMA, a release of sIL-6R from peripheral human T-cells was observed which
      was insensitive to the protein synthesis inhibitor cycloheximide. This release
      was accompanied by a decrease of membrane-bound (mb) IL-6R. After 24 h, however,
      the observed sIL6-R release did prove to be sensitive to cycloheximide. These
      results suggest that both shedding and denovo-synthesis may be responsible for
      the PMA-induced sIL-6R release. In contrast to PMA, neither anti-CD3, a positive,
      nor IL-10, a negative regulator of IL-6 release from T-cells affected the
      production of the sIL-6R. The differential regulation of sIL-6R and IL-6
      production by T-cells might be relevant for the immunomodulatory potential of the
      sIL-6R with respect to the interaction of T- and non-T-cells.

PMID- 9561919
TI  - T cell dependent B cell activation occurs during the induction of T cell anergy
      by staphylococcal enterotoxin B in mice.
AB  - Staphylococcal enterotoxin B (SEB) can activate specific T cell clones bearing
      specific TcR V beta domains together with MHC class II ligands on accessory
      cells. The release of proinflammatory cytokines is the consequence of this
      activation as well as the main pathological aspect involved in SEB infection.
      This current study looked at the active role of both T and B cells during the
      induction of anergy by SEB in vivo. Euthymic and nude BALB/c mice were injected
      with SEB and over a period of 8 days, cells from the spleen and sera from the
      blood were collected. After a single injection with SEB (50 micrograms/mouse), a
      transient increase of CD4+V beta 8+ T cells were detected after 2 days followed
      by a decrease after 4 days, which persisted until day 8. These clones were
      rendered anergic upon restimulation in vitro with SEB. Interestingly, cells taken
      out 2 days after SEB injection, exhibited reduced proliferation in response to
      Con A. However, this response gradually recovered on days 4, 6 and 8.
      Furthermore, early IgM antibody production (day 2) was observed after SEB
      injection. SEB-induced IgM antibody production in euthymic BALB/c was found to
      have specificity against SEB, cardiolipin (CL) and phosphatidylethanolamine (PE).
      SEB-treated nude mice did not produce antibody secreting cells in response to
      SEB, indicating that this process is T cell dependent.

PMID- 9561920
TI  - A rapid, quantitative enzyme-linked immunosorbent assay (ELISA) for the
      immunodiagnosis of Chagas' disease.
AB  - A rapid, quantitative enzyme-linked immunosorbent assay (ELISA) for the
      immunodiagnosis of Chagas' disease is described. The ELISA was standardized with
      the Falcon assay screening test (F.A.S.T.) system using a purified Trypanosoma
      cruzi epimastigote fraction (PEF) obtained by ion exchange chromatography. The
      ELISA technique and an indirect immunofluorescence (IIF) test were used to search
      for T.cruzi--specific IgG antibodies in 73 patients with chronic Chagas' disease,
      58 patients with heterologous infections and 20 healthy controls. The ELISA
      exhibited 98.6% sensitivity and 98.7% specificity, whereas the sensitivity and
      specificity of the IIF test were 94.5% and 96.2%, respectively. The excellent
      performance with regard to sensitivity and specificity, as well as the short
      assay time make the F.A.S.T. system--based ELISA with PEF a potentially useful
      tool in screening for antibodies against T. cruzi.

PMID- 9561921
TI  - Antinuclear antibodies (ANA) and complement fixing ANA in systemic connective
      tissue diseases.
AB  - Screening for antinuclear antibodies (ANA) with parallel tests for complement
      fixing ANA (C-ANA) reveal that C-ANA react either as strongly as or more strongly
      than ANA in most cases of systemic lupus erythematosus (SLE) and related
      disorders including CREST syndrome. But sera of drug induced LE and other ANA
      positive subjects have weak or no C-ANA. (P < 0.0005). Titrations with parallel C
      ANA/ANA tests of two cases reveal primarily ANA and less C-ANA reactions in a
      case of drug induced LE but in CREST syndrome both ANA and C-ANA tests yield
      elevated titers with stronger C-ANA reactions. These findings point to distinct
      immunochemical mechanisms in C-ANA and ANA reactions.

PMID- 9561922
TI  - Control of IgE responses. V. Oral administration of a synthetic derivative of the
      inner bacterial cell wall (SDZ 280.636) to sensitized mice induces isotype
      specific suppression of peak hapten specific IgE antibody forming cell responses,
      serum IgE levels and immediate hypersensitivity responses.
AB  - SDZ 280.636, a nontoxic diacyl glycerol derivative of muramyl dipeptide (MDP), a
      component of the inner bacterial cell wall, which is suitable for use in man,
      suppressed hapten specific IgE antibody forming cell (AFC) responses in spleen,
      serum levels of hapten specific IgE and hapten specific immediate
      hypersensitivity (i.h.) responses in skin, when fed to mice at the peak of a
      hapten specific IgE AFC response. In addition, serum levels of IL-6 appeared
      increased while IFN gamma was decreased. To induce these IgE responses, BALB/c
      mice were injected i.p. with BPO-KLH (benzylpenicilloyl-keyhole limpet
      hemocyanin) (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21 and
      42. Mice were fed (gavage) with either MDP or SDZ 280.636 (1.0 or 10 mg/kg) on
      day 44, or on days 44, 46 and 48, and killed on days 46 or 50. Numbers of BPO
      specific AFC in spleen, and serum levels of BPO specific immunoglobulins (IgG1,
      IgE and IgA) were determined (ELISPOT assay, ELISA). In addition, BPO specific IH
      responses were measured in these animals. Mice were injected in the right pinna
      with BPO-BSA (0.1 microgram) and in the left pinna with an equal volume of saline
      (0.05 ml). At 2 hr, pinnae were measured using a micrometer caliper. We found
      that 1 feeding with either MDP or SDZ 280.636 abrogated IgE AFC responses and
      dramatically suppressed serum levels of IgE, both in isotype specific fashion,
      and suppressed IH responses (> 50%). 3 feedings with SDZ 280.636 also abrogated
      IgE AFC responses and further decreased serum levels of IgE. In contrast to SDZ
      280.636, 3 treatments with MDP had opposite effects in that IgE AFC responses and
      serum levels of IgE dramatically increased. A single treatment with SDZ 280.636
      appeared to increase serum levels of IL-6 up to three fold, while IFN gamma
      levels decreased. Our data suggest that SDZ 280.636 may be useful in the
      therapeutic and prophylactic management of human atopic disease such as allergic
      rhinitis, asthma, and other atopic diseases.

PMID- 9561923
TI  - Eotaxin increases the expression of CD11b/CD18 and adhesion properties in IL5,
      but not fMLP-prestimulated human peripheral blood eosinophils.
AB  - A selective recruitment of eosinophils to sites of inflammation is claimed to be
      controlled by regulation of cytokines, chemokines and adhesion molecules. In
      animal models, eotaxin has been suggested to be a potent chemokine since it in
      cooperation with interleukin-5 induce selective chemotaxis and infiltration of
      eosinophils to lung tissue after an allergen provocation. We have investigated
      the in vitro effect of eotaxin on human peripheral blood eosinophils with respect
      to CD11b/CD18 expression and adhesion properties to the matrix protein
      fibronectin. We did not find any effect of eotaxin per se on CD11b/CD18
      expression, neither on eosinophils from healthy subjects nor from patients with
      asymptomatic pollen related asthma. However, eotaxin significantly upregulated
      the quantitative level of CD11b/CD18 and increased the adhesion to fibronectin in
      eosinophils from healthy subjects preincubated in vitro with interleukin-5, but
      not in eosinophils preincubated with fMLP. Moreover, eosinophils harvested 24
      hours after an in vivo allergen inhalation provocation in asthmatics, upregulated
      CD11b/CD18 after in vitro incubation with eotaxin alone.

PMID- 9561924
TI  - Tubular cell and HIV-1 gp120 interaction products promote migration of monocytes.
AB  - Renal interstitial accumulation of monocytes is an important feature of HIV
      associated nephropathy. We studied the effects of proximal tubular cell products
      (TCP) and proximal tubular cell-gp120 interaction products (TC-120IP) on the
      migration of monocytes across a modified Boyden chamber. TC-120IP promoted (P <
      0.001) the migration of monocytes when compared with TCP (TCP, 45.0 +/- 5.9 vs.
      TC-120IP, 192.3 +/- 39.5 migrated monocytes/field). This effect of TC-120IP on
      monocyte migration was dose dependent. Anti-MCP-1 (TCP, 24.7 +/- 2.6; TC-120IP,
      82.3 +/- 5.5; TC120-IP + anti-MCP-1 antibody, 46.5 +/- 3.5 migrated
      monocytes/field) as well as anti-TGF-beta antibodies (TCP, 25.8 +/- 3.4; TC120
      IP, 80.3 +/- 6.9; TC-120IP + anti-TGF-beta antibody, 43.8 +/- 5.6 migrated
      monocytes/field) partly attenuated TC-120IP-induced migration of monocytes across
      a filter. Moreover, anti-MCP-1 and anti-TGF antibodies showed an additive
      inhibitory effect on TC-120IP-induced migration of monocytes across a filter.
      These results suggest that TC-120IP-induced migration of monocytes may be
      mediated through the generation of MCP-1 and TGF-beta by tubular cells. The
      present study provides the basis for a hypothesis that HIV-1 gp120 protein may be
      contributing to the infiltration of monocytes in the renal interstitium of
      patients with HIV-associated nephropathy.

PMID- 9561926
TI  - Induction of secretory phospholipase A2 confirms the systemic inflammatory nature
      of adjuvant arthritis.
AB  - Adjuvant arthritis (AA) is an accepted model of inflammatory arthritis. Until
      now, however, there is little information about inflammatory mediators,
      specifically in relation to the arachidonic acid cascade in AA. Our objective was
      to study the expression of secretory (sPLA2) and cytosolic (cPLA2) phospholipases
      A2 in various organs during the course of AA. AA was induced in Lewis rats which
      were sacrificed at days 0, 7, 14, 21, 28 and 42. Expression of sPLA2 mRNA and
      protein and mRNA of cPLA2 in paws, regional lymph nodes, spleen, liver, lungs and
      aorta was investigated. Serum sPLA2 activity increased from 15213 +/- 1131 to a
      maximum of 32,455 +/- 4109 nmol/30' on day 21. Maximal increase in sPLA2 mRNA in
      paws, lung and aorta was observed on day 14, and in the lymph nodes and spleen on
      day 28. In the liver, trace levels were found with no corresponding protein
      expression. In paws, lung, aorta and lymph nodes maximum increase in sPLA2
      protein was noted on day 14 whereas the spleen showed constant sPLA2 protein
      level during AA. cPLA2 mRNA detected in all organs, did not significantly change
      during the course of AA, with the exception of regional lymph nodes where the
      message increased between 14 and 28 day. Induction of mRNA and protein of sPLA2
      in several organs is an evidence that AA is a systemic inflammatory process. The
      parallelity of the sPLA2 expression to the severity of inflammatory process,
      implies that sPLA2 may play pathogenic role in AA. Lack of enhancement of cPLA2
      mRNA may mean that this enzyme is either not induced in AA, or it increases
      earlier in the course of the inflammatory process.

PMID- 9561925
TI  - Differential production of chemokines by phagocytosing rat neutrophils and
      macrophages.
AB  - In this study, rat neutrophils and macrophages produced cytokine-induced
      neutrophil chemoattractants (CINCs) and rat macrophage inflammatory protein-1
      alpha (MIP-1 alpha) in different patterns during phagocytosis of heat-killed
      yeast cells in vitro. The cultured supernatants of the phagocytosing rat
      neutrophils and macrophages had chemotactic activities toward neutrophils, and
      the chemotactic potencies were markedly inhibited by anti-CINCs IgGs or/and anti
      MIP-1 alpha IgG, suggesting that CINCs and MIP-1 alpha are major neutrophil
      chemoattractants produced by the phagocytosing neutrophils and macrophages.
      Dexamethasone suppressed the production of CINCs and MIP-1 alpha by the
      phagocytosing cells in a dose-dependent manner. Our results demonstrate
      significant differences in the production of CINCs and MIP-1 alpha by neutrophils
      and macrophages during phagocytosis of yeast cells and thus may suggest the
      different contribution of each chemokine to neutrophil recruitment in the
      processes of inflammation in rats.

PMID- 9561927
TI  - Neutrophil behavior following exposure to in vivo or in vitro zinc in normal and
      acutely-inflamed rats: studies on lysozyme secretion, superoxide anion release
      and platelet adhesion.
AB  - The mechanism was studied of the anti-inflammatory effect of oral zinc (114
      mg/kg/day of elemental metal, given for 14 days) on the development of the
      carrageenan-induced paw oedema of the rat, and the impact of in vivo treatment on
      the activity of neutrophils isolated from the blood of inflamed and non-inflamed
      animals. The effects of the in vitro incubation with the metal on either non
      inflamed or inflamed neutrophils coming from zinc-untreated rats were also
      examined. It was found that the administration of oral zinc inhibited markedly
      the process of ex vivo adhesion of the cells obtained from the inflamed rats (an
      observation confirmed by the in vitro experiments). In vitro release of lysozyme
      and superoxide anion productions were measured: in the absence of zinc, the 30'
      of pre-incubation carried out before stimulating with PMA did not influence the
      cell's reactivity of the non-inflamed neutrophils. It was, on the contrary,
      capable of significantly reducing that of the inflamed ones. As a consequence, it
      is quite difficult to properly interpret the data obtained studying the activity
      of the cells exposed to the metal in vitro.

PMID- 9561928
TI  - Azithromycin impact on neutrophil oxidative metabolism depends on exposure time.
AB  - Several antimicrobial agents have already been investigated relating to their
      influence on neutrophil ROS generation. Azithromycin provides, a dose-related
      anti-oxidant effect, after 15 min incubation, with the stimulating agent FMLP, as
      well with PMA or S. aureus. This finding was however obtained with concentrations
      not considered in therapeutics. Since short incubation times are not
      representative of the physiological situation, and since azithromycin is
      characterized by prolonged high concentrations within phagocytes, the same
      experiments were performed over 2 and 4 h exposures. A time-dependent anti
      oxidant effect was then reported. The maximum effect was obtained with PMA (IC50
      were 856 and 30 micrograms/ml for 15 min and 4 h incubation times respectively).
      Time-dependent modifications of neutrophil oxidative metabolism seem to be
      correlated with intracellular concentrations. Depressed oxidative metabolism
      might be related neither to azithromycin cellular toxicity, nor to superoxide
      scavenging properties. By increasing exposure periods, therapeutic concentrations
      could therefore lead to an anti-inflammatory effect, potentially of clinical
      interest since associated with bacteriostatic activity.

PMID- 9561929
TI  - Smoke-induced inhalation injury: effects of retinoic acid and antisense
      oligodeoxynucleotide on stability and differentiated state of the mucociliary
      epithelium.
AB  - Rabbit tracheal explants, exposed to burning pine wood smoke, were cultured in a
      chemically defined medium with and without retinoic acid (+/- RA). Exposures of
      15-20 minute led to RA-independent degeneration of the mucociliary epithelial
      sheath. In 10 minute exposures tissue integrity was retained, but epithelial
      morphology changed from normal pseudostratified columnar to the flattened
      appearance typical of the squamous phenotype. Despite the dramatic shift in
      morphology, explants exhibited normal RA-dependent mucin gene expression
      characteristic of the mucociliary phenotype. Furthermore, electron micrographs
      showed continued presence of both secretory granules and cilia. RA(+) cultures
      also showed a normal pattern of adherent epithelial cells. In RA(-) cultures,
      however, there were prominent intercellular spaces indicating an RA dependence
      for maintaining adhesive contacts following smoke exposure. An 18-mer mucin
      antisense oligomer that suppressed mucin gene expression also unexpectedly
      blocked the smoke induced metaplasia in RA(+) cultures, but the sense oligomer
      had no effect.

PMID- 9561932
TI  - Interpersonal schemata in child psychotherapy: a cognitive-interpersonal
      perspective.
AB  - Presents a cognitive-interpersonal framework for child psychotherapy derived from
      attachment theory. Interpersonal schema, conceptualized as expectations regarding
      others' probable responses to the self, are posited as a key mediating mechanism
      linking past interpersonal experience with current social-emotional functioning,
      and as an important target for intervention. Three schema-based models of
      pathogenic process are examined: preemptive information-processing, schema
      triggered affect, and schema-primed interpersonal and emotion-regulation
      strategies. Implications for assessment of and intervention with interpersonal
      schema are considered. Preventive, compensatory, and remedial intervention
      strategies are proposed.

PMID- 9561930
TI  - Effect of interleukin-8 and monocyte chemotactic protein-1 on adhesion of
      circulating granulocytes and monocytes from asthma patients to human venous
      endothelial cells.
AB  - The adhesive interactions between phagocytes and endothelial cells (EC) can be
      modulated by inflammatory cytokines and chemotactic proteins which are released
      during an inflammatory response. The aim of the present study was to investigate
      first whether the adhesive properties of granulocytes and monocytes from asthma
      patients for vascular endothelial cells differ from those of phagocytes from
      healthy individuals. Furthermore, we studied whether the chemokines interleukin-8
      (IL-8) and monocyte chemotactic protein-1 (MCP-1) can affect the binding of
      phagocytes to EC. No differences were observed in binding of phagocytes from
      asymptomatic or symptomatic asthma patients and from healthy individuals to non
      stimulated or cytokine-stimulated EC. Incubation of granulocytes with IL-8 did
      not influence their adhesion to non-stimulated EC but inhibited the adhesion of
      granulocytes to IL-1-stimulated EC. Incubation of monocytes with MCP-1 did not
      affect their adhesion to non-stimulated or cytokine-stimulated EC. Our results
      indicate that adhesion of phagocytes to EC depends on the activation state of the
      endothelial cells but not on the origin of the phagocytes, since there were no
      differences in the adhesion of phagocytes from asthma patients and healthy
      individuals to non-stimulated or cytokine-stimulated EC.

PMID- 9561933
TI  - Linguistic psychotherapy research: new directions and promising findings.
AB  - Language configures experience and is our primary instrument of meaning making.
      Its central role in the construction of our subjective and interpersonal worlds
      provides the rationale for investigating its forms and functions in
      psychotherapy. Three clinically relevant dimensions of language (i.e.,
      connectivity, modality, and complexity) are outlined and several examples of
      linguistic variables on each dimension are defined. Linguistic studies of
      psychotherapy are then presented in terms of focal points of assessment:
      pretherapy, intherapy, and posttherapy. At each focal point, innovative
      applications of linguistic variables are presented, often in contexts that permit
      direct contrast with more traditional methodologies. Promising preliminary
      results suggest that linguistic research can help to better differentiate and
      describe patient psychopathology at pretherapy, therapist and patient processes
      in therapy, and patient gains at posttherapy.

PMID- 9561934
TI  - Cognitive-behavioral play therapy.
AB  - Discusses cognitive-behavioral play therapy (CBPT), a developmentally sensitive
      treatment for young children that relies on flexibility, decreased expectation
      for verbalizations by the child, and increased reliance on experiential
      approaches. The development of CBPT for preschool-age children provides a
      relatively unique adaptation of cognitive therapy as it was originally developed
      for adults. CBPT typically contains a modeling component through which adaptive
      coping skills are demonstrated. Through the use of play, cognitive change is
      communicated indirectly, and more adaptive behaviors can be introduced to the
      child. Modeling is tailored for use with many specific cognitive and behavioral
      interventions. Generalization and response prevention are important features of
      CBPT. With minor modifications, many of the principles of cognitive therapy, as
      delineated for use with adults, are applicable to young children. Case examples
      are presented to highlight the application of CBPT. Although CBPT has a sound
      therapeutic base and utilizes proven techniques, more rigorous empirical scrutiny
      is needed.

PMID- 9561931
TI  - Expression of adhesion molecules on granulocytes and monocytes from patients with
      asthma stimulated in vitro with interleukin-8 and monocyte chemotactic protein-1.
AB  - Upregulation of adhesion molecule expression on endothelial cells (EC) and
      circulating leukocytes, by locally produced inflammatory mediators, may result in
      the enhanced infiltration of leukocytes into tissue, e.g. the airways of asthma
      patients. The present study investigates whether the expression of adhesion
      molecules on granulocytes and monocytes from asthma patients is affected by
      chemotactic factors, i.e. interleukin-8 (IL-8) and monocyte chemotactic protein-1
      (MCP-1). Flow cytometric analysis showed that the intrinsic expression of the
      various adhesion molecules on peripheral blood phagocytes from asthma patients
      was not different from that of healthy individuals. However, stimulation of
      monocytes with MCP-1 resulted only in upregulation of the expression of CD14 on
      monocytes from symptomatic asthma patients but not on monocytes from asymptomatic
      asthma patients and healthy individuals. Stimulation of granulocytes with IL-8
      did not change the expression of the various beta 1- and beta 2-integrin
      molecules, such as VLA-4, LFA-1, CR3 and p150,95. Since earlier studies have
      shown that CD14 on monocytes mediates monocyte adhesion to activated vascular EC
      the present findings suggest that during the active phase of asthma upregulation
      of CD14 on monocytes by MCP-1 may lead to an increased adhesion of monocytes to
      vascular endothelium and their subsequent transendothelial migration into the
      tissue of the airways.

PMID- 9561935
TI  - Efficacy of parent-child interaction therapy: interim report of a randomized
      trial with short-term maintenance.
AB  - Describes interim results of a study examining the effectiveness of parent-child
      interaction therapy (PCIT) with families of preschool-age children with
      oppositional defiant disorder. Following an initial assessment, 64 clinic
      referred families were randomly assigned to an immediate treatment (i.t.) or a
      wait-list control (WL) condition. Results indicated that parents in the IT
      condition interacted more positively with their child and were more successful in
      gaining their child's compliance than parents in the WL condition. In addition,
      parents who received treatment reported decreased parenting stress and a more
      internal locus of control. Parents in the IT group reported statistically and
      clinically significant improvements in their child's behavior following PCIT. All
      families who received treatment reported high levels of satisfaction with both
      the content and process of PCIT. Preliminary 4-month follow-up data showed that
      parents maintained gains on all self-report measures.

PMID- 9561936
TI  - Developmentally based psychotherapies: comments and observations.

PMID- 9561937
TI  - A comment on psychotherapy integration in the treatment of children.
AB  - Interest in psychotherapy integration, which has developed into an ongoing
      movement in the past decade or two, now appears to be capturing the interest
      among therapists and researchers in the clinical child area. The articles in this
      section deal specifically with the integration of basic research on language and
      cognition into the clinical arena, and the complementary use of concepts and
      interventions from different schools of thought. In commenting on these
      contributions, I have underscored the importance of using a broader historical
      and conceptual perspective, so that we can advance, rather than rediscover, what
      we already know.

PMID- 9561938
TI  - Dysphoric interpersonal schemata and preadolescents' sensitization to negative
      events.
AB  - Addresses the hypothesis that interpersonal schemata sensitize dysphoric
      youngsters to negative social information and contribute to the amplification of
      depressive symptoms. Sensitization was conceptualized as involving multiple
      components, including heightened anticipation, selective focus, and rapid
      information processing. Four studies with separate samples of preadolescents and
      early adolescents were conducted. Results from 3 laboratory-based studies
      indicated that depressed and dysphoric youngsters evince relatively negative
      interpersonal schemata, and that these schemata are related to the 3 components
      of sensitization. A short-term prospective study examined the hypothesis that
      dysphoric interpersonal schemata moderate the emotional impact of a normative
      social stressor, the transition to high school. Results indicated that youngsters
      who entered the transition with relatively negative schema experienced the
      transition as more stressful than youngsters with relatively positive schema, and
      that negative interpersonal schema amplified the effects of stress on depressive
      symptoms.

PMID- 9561939
TI  - Testing the utility of the anxiety sensitivity construct in children and
      adolescents referred for anxiety disorders.
AB  - Tested the utility of assessing anxiety sensitivity in children by investigating
      the incremental validity of the Childhood Anxiety Sensitivity Index (CASI) in a
      sample of clinic-referred children and adolescents ages 6 to 17 (N = 280). In the
      first test we examined whether the CASI would predict variance in trait anxiety
      beyond that predicted by measures of manifest anxiety and fear in children ages 6
      to 11 (n = 202) and adolescents ages 12 to 17 (n = 78). In the next test, we
      examined whether the CASI would predict variance in fear beyond that predicted by
      a measure of trait anxiety for both age groups. In addition, age was tested as a
      continuous moderator of the CASI's incremental validity. No evidence was found to
      suggest that age systematically influences the CASI's incremental validity in the
      age ranges for which the CASI was designed. We discuss the results in terms of
      the utility of the CASI with younger and older age groups of children and the
      importance of such a measure for investigating the development of anxiety
      disorders in children.

PMID- 9561940
TI  - Stress and coping as predictors of children's divorce-related ruminations.
AB  - Examined stress and coping variables as predictors of divorce-related ruminations
      in children whose parents had recently divorced. Simultaneous multiple regression
      was used to analyze the cross-sectional data of 351 children of divorce. Divorce
      related stressful events and threat appraisal were positively related to
      children's ruminations. A prospective longitudinal design was employed to predict
      rumination at Time 2 (T2) controlling for Time 1 (T1) rumination. Efficacy of
      coping was negatively related to T2 rumination after controlling for T1
      rumination and all other predictors. This study also provided descriptive data on
      the frequency of children's divorce-related ruminations.

PMID- 9561941
TI  - Assessing parent attributions for child behavior using open-ended questions.
AB  - Assessed parent attributions for child behavior using open-ended questions. Sixty
      one parents of children with attention deficit hyperactivity disorder (ADHD) and
      49 parents of nonproblem children participated. An open-ended, thought-listing
      question asked following child behavior indicated that parents spontaneously
      offer causal attributions for their children's behavior. Responses to a second
      open-ended question asking specifically for attributions for the child behavior
      indicated that both groups of parents attributed prosocial (PRO) child behaviors
      more than problem behaviors to internal, controllable, and stable causes or to
      the external situation and attributed problem behaviors most often to
      uncontrollable and unstable causes within the child or to factors within the
      parent. Compared with parents of nonproblem children, parents of children with
      ADHD were less likely to see themselves as the cause of child behavior and were
      more likely to mention medication. Analyses indicated that, although attributions
      elicited by rating scales were related to attributions provided in an open-ended
      format, each method provided unique information.

PMID- 9561942
TI  - Youth attitudes toward guns and violence: relations with sex, age, ethnic group,
      and firearm exposure.
AB  - Investigated relations between young people's scores on the Attitudes Toward Guns
      and Violence Questionnaire (AGVQ; Shapiro, Dorman, Burkey, Welker, & Clough,
      1997), demographic variables, and exposure to firearms and violence. 1,164
      students, Grades 3 to 12, from an urban, suburban, parochial, and private school
      system completed anonymous self-report questionnaires in their classrooms. Boys
      produced higher AGVQ scores than did girls. Scores were similar in Grades 3 and
      5, were much higher in Grade 6 than in Grade 5, and were similar in Grades 6 and
      above. This pattern was found across sex, race, and school system. African
      Americans obtained higher scores than Caucasians on the AGVQ and on 2 of its 4
      factors. Students in the urban public schools produced higher scores than did
      youth in the other school systems. Both traumatic and nontraumatic exposure to
      firearms were associated with high AGVQ scores. Sex, grade, and firearm exposure
      were associated with relatively large differences, while ethnic group and school
      system were associated with relatively small differences.

PMID- 9561943
TI  - A comparison of two measurements of child compliance with normal preschool
      children.
AB  - Observed normal preschool children from 2 through 5.9 years of age and their
      mothers using 2 established measurements of child compliance: the Compliance Test
      and the Clinic Task Analog. The diagnosis of oppositional defiant disorder as
      defined by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.,
      American Psychiatric Association, 1994) currently requires subjective integration
      of interview, questionnaire, and behavioral data. Knowledge of normal child
      behavior within a parent-controlled task context is needed. Normal 4- and 5-year
      olds were found to be more compliant than were normal 2- and 3-year olds; no sex
      effects were detected. The Compliance Test yielded stronger age associations,
      better observer reliability, and more individual differences than the Clinic Task
      Analog. Clinic Task Analog data masked child compliance, probably as a result of
      maternal instruction-giving style. The Compliance Test is recommended for
      diagnostic purposes over the Clinic Task Analog.

PMID- 9561944
TI  - Underlying dimensions and psychometric properties of the Eating Behaviors and
      Body Image Test for preadolescent girls.
AB  - Developed a rating scale to measure body image satisfaction and eating behaviors
      and disturbances in preadolescent girls and evaluated the psychometric properties
      of the instrument. The Eating Behaviors and Body Image Test (EBBIT) for
      preadolescent girls was administered to 291 fourth-, fifth-, and sixth-grade
      girls to identify the measure's factor structure. Body Image Silhouettes (BIS;
      Childress, Brewerton, Hodges, & Jarrell, 1993) were also administered, and height
      and weight measurements were obtained. Although four factors were predicted
      (maladaptive thoughts about body size, restrictive eating, bingeing, and
      compensatory behavior for overeating), corresponding to adult criteria for the
      diagnoses of anorexia and bulimia, factor analysis of the EBBIT suggested only
      two factors: Body Image Dissatisfaction/Restrictive Eating and Binge Eating
      Behaviors. Only two compensatory behaviors (exercising to burn off food eaten and
      skipping meals after overeating) loaded on the scale, and they loaded on the Body
      Image Dissatisfaction/Restrictive Eating factor. Internal consistency and test
      retest reliabilities were adequate to good, and initial validity of the scale was
      established by using scores on the Body Image Silhouettes, body mass index
      ratios, age, and race as predictors of EBBIT scores.

PMID- 9561945
TI  - Making a difference--is journal publication enough?

PMID- 9561946
TI  - A new approach to substance abuse treatment. Adolescents and adults with ADHD.
AB  - Adolescents and young adults with Attention Deficit Hyperactivity Disorder (ADHD)
      are not only at risk for drug and alcohol dependence, but are also difficult to
      maintain in a chemical dependency facility due to disruptive behaviors. Such
      patients may be "hyperaroused," a term coined by the field of occupational
      therapy, but oppositional behaviors hide their physical and emotional
      overreactivity. Thirty years ago, occupational therapist Dr. Jean Ayres developed
      Sensory Integration (SI) techniques that are traditionally used with children
      under 12 years of age who are diagnosed with learning disabilities, autism, and
      ADHD. Many of the chemically dependent adolescent and young adult patients with
      ADHD who are in treatment display characteristics similar to those of children
      traditionally targeted for this therapy. Techniques used by occupational
      therapists trained in SI were adapted to treat hyperarousal and overreactivity to
      the environment in chemically dependent adolescents and young adults, in order to
      maintain them in the treatment environment until they were ready to graduate. The
      techniques were successful in maintaining and educating patients about ADHD and
      chemical dependency.

PMID- 9561947
TI  - Current management of infectious complications in the injecting drug user.
AB  - The diagnosis and management of infectious complications associated with
      injection drug use (IDU) are among some of the more challenging aspects of
      working with substance abusing populations. As the population of injection drug
      users age, we expect the number and severity of these complications to increase.
      Commonly seen infections, such as bacterial endocarditis and bacterial infections
      of bones, joints, and soft tissue, are now frequently complicated by concurrent
      immunodeficiency. Parenterally and sexually transmitted viral hepatitis is
      responsible for significant IDU morbidity and mortality. The human
      leukemia/lymphoma virus types I and II are increasing in prevalence in the IDU
      with uncertain long-term clinical effects. Immune dysfunction has been described
      in the IDU for decades, but the impact of host immune compromise on the
      transmission and the course of HIV-1 has yet to be fully appreciated. The
      integration of the treatment of substance abuse and its concurrent psychiatric
      disorders with the management of infectious complications, including
      immunodeficiency, promises to improve patient compliance with possible savings of
      overall medical costs.

PMID- 9561948
TI  - A model for dual disorder treatment in acute psychiatry in a VA population.
AB  - One model for addressing the dual disorders of substance abuse and a concomitant
      mental disorder in an acute-psychiatry inpatient ward of a VA Medical Center
      utilized psychoeducation and ward policies to empower patients to make decisions
      affecting their recoveries. Existing staff shared responsibilities for
      implementing activities and creating ward milieu that supported psychiatric
      patients toward a life free of alcohol and drugs as they gained in acceptance of
      responsibility for the management of their mental disorders. Integrated
      programming assisted patients in constructing a meaningful path of recovery out
      of multiple treatment approaches and philosophies. Treatment principles, ward
      policies, and goals for an integrated acute-psychiatry model evolved over 4
      years. Designed from a consumer-oriented "strengths perspective," patients
      responded to the new programming with satisfaction and gratitude. Recent
      adaptation of these policies, principles, and goals to a newly instituted
      continuous-care treatment program indicates the appropriateness of their
      application for outpatient dual disorder treatment and programming as well.

PMID- 9561949
TI  - Novel antipsychotic medications and the treatment of comorbid substance abuse in
      schizophrenia.
AB  - Comorbid substance abuse (SA) in schizophrenia is a significant problem.
      Moreover, these patients are particularly difficult to treat. This report reviews
      the pharmacological management of comorbid SA and schizophrenia and a case report
      is provided to illustrate the potential of novel antipsychotic medications.

PMID- 9561950
TI  - Modified therapeutic community treatment for homeless dually diagnosed men. Who
      completes treatment?
AB  - We studied a modified therapeutic community designed for the treatment of
      patients with combined substance abuse and psychiatric disorders. This model has
      been ap117117plied on a limited basis in clinical practice, and little is known
      about the characteristics of patients who are likely to complete the prescribed
      stay in such a program. In this report, we present characteristics of 189
      homeless dually diagnosed men who entered a shelter-based, modified therapeutic
      community with a prescribed 6-month stay. Thirty-four percent of admissions
      completed the prescribed stay. These patients were more likely to have fewer
      inpatient psychiatric admissions and more job experience than those who did not
      complete their stay. Findings are discussed in terms of their similarities and
      differences to findings from traditional therapeutic communities for the singly
      diagnosed.

PMID- 9561951
TI  - The impact of depression on the outcome of addictions treatment.
AB  - The objectives of this study were to examine the prevalence and presentation of
      depression among patients with substance use disorders, and to explore the
      relationship between depression and the outcome of addictions treatment. Seventy
      five patients were consecutively recruited upon entering addictions treatment,
      and were assessed by clinical and semi-structured interviews, Hamilton Rating
      Scale for Depression, Global Assessment Scale, and Beck Depression Inventory. At
      intake, 22.4% of patients had primary depressive disorders, 8.4% had substance
      induced depressions, and 5.6% had mixed features of primary and substance-induced
      depressions. Female and alcoholic patients were more likely to suffer from both
      primary and substance-induced depressions. At 3 months, 93.3% of patients were
      reinterviewed. Depressed patients had longer duration of abstinence and greater
      decreases in symptomatology. Patients with substance-induced depression achieved
      almost complete discontinuation of primary substance use. Depression had a
      significant impact on addictions treatment outcome, but many important predictors
      of outcome have not yet been identified.

PMID- 9561952
TI  - Drug abuse in Cuba.

PMID- 9561953
TI  - Psychopathology, treatment completion and 5 years outcome. A prospective study of
      drug abusers.
AB  - Two hundred Norwegian drug abusers who consecutively applied for treatment in a
      Phoenix-House-type of therapeutic community, were interviewed in intake and
      personally followed up, on average, 5 years after (response rate 79%). The year
      prior to follow-up, 20% had no/light use of substances and 56% heavy abuse,
      including the deceased (12.4%). Personality disorders and psychopathology at
      application did not directly predict either substance abuse problems nor level of
      social functioning, but were mainly related to the risk of death. Treatment
      completion was positively related to the 5-year outcome of social functioning,
      but not to substance abuse problems. Our findings indicate the need for more
      systematic training in how to control the use of substances in the Phoenix House
      model. One should also offer a more longstanding outpatient programme of social
      skills training, aiming at following these clients for years.

PMID- 9561954
TI  - An outcome study of Missouri's CSTAR alcohol and drug abuse programs.
AB  - The Comprehensive Substance Abuse Treatment and Rehabilitation (CSTAR) program is
      described, and a study of its services is presented. The CSTAR program is a
      community program with wrap-around services and intensive case management. Eleven
      domains typically affected by substance abuse were measured, plus satisfaction
      with treatment services. A retrospective study of 280 clients at 10 facilities
      was done, and results analyzed separately by General Programs. Women with
      Children programs, and Adolescent programs. A small sample of clients who were
      early in their treatment was re-interviewed 90 days later. Data were also
      examined according to length of stay in the program. Results were consistently
      positive, and increased with length of time in the program.

PMID- 9561955
TI  - Current approaches to drug treatment for women offenders. Project WORTH. Women's
      Options for Recovery, Treatment, and Health.
AB  - This paper reports ethnographic findings on current approaches to drug treatment
      for women offenders. Drug treatment programs serving women offenders have
      employed a range of therapeutic interventions to address drug use and
      criminality. However, programs have recently begun to address clients'
      victimization experiences as an integral if not central feature of women's drug
      use and participation in illegal activities. Treatment approaches at eight
      corrections- and community-based programs in New York City and Portland, Oregon
      are described. Data were obtained from life history interviews conducted with 60
      women and observation of treatment activities. Developments in treatment
      approaches in corrections versus community settings and gender-specific services
      are described. Programs have tailored treatment approaches for women offenders by
      offering incest and domestic violence survivor groups, assigning therapeutic
      rather than punitive sanctions, and training corrections staff to support
      treatment goals.

PMID- 9561956
TI  - [Intrathecal interferon therapy in chronic echovirus meningoencephalitis in
      Bruton type agammaglobulinemia].
AB  - A 9-year-old body with X-linked agammaglobulinemia developed chronic enteroviral
      meningoencephalitis (CEMA) caused by echovirus type 6. Intravenous treatment with
      selected immunoglobulin charges containing high titers against echovirus type 6
      or combination with beta-interferon did not result in improvement. After
      implantation of a Rickham reservoir and periodical administration of
      intraventricular and intravenous immunoglobulin the virus recurred rapidly each
      time treatment was stopped. After 20 months of treatment the patient received a
      combined therapy with beta-interferon and selected immunoglobulin. Both drugs
      were given by lumbar puncture, intravenously and via Rickham reservoir.
      Subsequently echovirus type 6 could not be isolated in culture or PCR.
      Cerebrospinal fluid pleocytosis disappeared. The remission is lasting for more
      than three years. Intrathecal and intraventricular beta-interferon therapy for
      CEMA is being reported for the first time. Facing the unfavourable prognosis of
      the disease this mode of treatment is a new therapeutic approach following
      failure of other therapies.

PMID- 9561957
TI  - [Acute hematogenous osteomyelitis in childhood--correlation of clinical aspects,
      diagnostic parameters, therapy and prognosis].
AB  - BACKGROUND: Acute hematogenous osteomyelitis is a common disease in childhood. If
      treated early, conservative management is possible in most cases. During recent
      decades, clinical picture, diagnostic techniques and treatment have changed due
      to various reasons, e.g. previous antibiotic treatment. New laboratory tests and
      improved imaging techniques such as magnetic resonance imaging enable an earlier
      diagnosis and thus an earlier onset of treatment and improve the prognosis of
      hematogenous osteomyelitis. Outcome has also been improved by new antibiotics
      with enhanced activity against staphylococci. METHOD: The records of 34 children
      aged 3 weeks to 172 months with acute hematogenous osteomyelitis were evaluated
      retrospectively. In some cases, the data were completed by phone calls with
      parents and family physicians. The results were compared with the current
      literature. RESULTS AND CONCLUSIONS: If diagnosed and treated early, acute
      hematogenous osteomyelitis in childhood has a good prognosis. For primary
      diagnosis, the clinical picture, parameters of inflammation and magnetic
      resonance imaging or scintigraphy are useful. The course of the disease can be
      assessed by clinical signs and the erythrocyte sedimentation rate. Complications
      can be recognized by conventional radiography and sonography. Initial antibiotic
      treatment should be carried out parenterally for at least 3 weeks. An exclusively
      oral treatment is not recommended.

PMID- 9561958
TI  - [Intestinal infection, the most frequent cause of invagination in childhood:
      results of a 10-year clinical study].
AB  - BACKGROUND: Intussusception is the most common cause of an acute abdomen in early
      childhood. 90% of all intussusceptions were thought to be idiopathic, because no
      lead points could be evaluated. PATIENTS: In our study we examined 148 children
      (93 boys and 55 girls) between 2. month and 18. years of age with 155
      intussusceptions. METHOD: Besides epidemiological features and patients history
      we determined systematically all symptoms which occurred since the beginning of
      sickness. We performed ultrasound examinations before and after hydrostatic
      reduction with each child in order to find pathologic lead points. Microbiologic
      stool examination could be carried out at 99 specimen. RESULTS: 41 of 155
      children with intussusception (26.5%) showed a pathologic finding next to the
      intussusception, with 29 children (18.7%) suffering from mesenteric
      lymphadenitis. 60.6% of examined stool specimen were abnormal. The most common
      germs were adenovirus, yersinia and staphylococcus aureus. Abdominal pain was the
      main symptom and was found in 72.6% of all children. 21% suffered from the
      classic trias abdominal pain, vomiting and rectal bleeding. 21.9% had diarrhea
      and 18% fever and signs of inflammation as unspecific symptoms. CONCLUSIONS: In
      our study we found mesenteric lymphadenitis as the most common lead point in
      intussusception. In conclusion with 60.6% pathologic germs in the examined stool
      specimen we assume gastrointestinal infection as the main cause of
      intussusception in childhood.

PMID- 9561959
TI  - [Central venous indwelling catheter systems in pediatric oncology from the
      surgical viewpoint].
AB  - A total of 307 central venous access devices were implanted by open surgery in
      268 pediatric oncology patients. Their data were retrospectively evaluated from a
      surgical point of view. The cumulative duration of implantation of 116
      subcutaneous tunneled Catheter (STC) was 12,206 days and 45,524 days for 191
      portsystems. According to the duration in each group, ports were superior to STC
      when infection, complication and occlusion were taken into consideration.
      Infection of the ports was more frequent in children under 3 years than in older
      patients. Conversely, in the STC-group, children over 10 years presented with the
      highest rate of infection episodes. The number of complications was high in young
      children for both types of catheter, decreasing with age. Occlusion rates were
      similar for both systems and were not age related. However, thrombolysis was more
      successful in portsystems and few catheters had to be removed for this reason.
      The age-related data of the presented study are discussed with regard to the
      surgical procedure. Recommendations are made concerning the adequate choice of
      catheter system, the surgical technique and postoperative management.
      Additionally, the medicotechnical aspect of different catheter types is discussed
      and some suggestions and/or requests are directed to the industrial developing
      laboratories.

PMID- 9561960
TI  - [Hearing screening of newborn infants at risk for perinatal hearing damage].
AB  - 630 neonates with risk factors of perinatal hearing impairment were screened of
      hearing loss by means of registration of transient otoacoustic emissions before
      discharge from the newborn nursery. Neonates were screened additionally by means
      of brainstem evoked response audiometry, if they had bilateral negative
      emissions. 810 healthy neonates were screened as control group. The
      investigations were carried out in incubator after the feeding of neonates. The
      prevalence of a bilateral negative cochlear response was 5.2% in the risk babies
      and 1.7% in healthy neonates. Neonates are high risk patients for hearing loss if
      they show craniofacial anomalies including alcohol embryofetopathy, connatal
      infections, or very low birth weight babies with additional risk factors. The
      pedaudiological control investigations of the babies with a negative bilateral
      cochlear response delivered in the risk group 15 cases (2.4%) with an important
      hearing impairment and in the healthy neonates 2 cases (0.25%) respectively.
      Prevalence and importance of perinatal hearing impairment explains the necessity
      of detection in the neonatal period.

PMID- 9561961
TI  - [Case example: malignant infantile osteopetrosis--pathogenesis and therapeutic
      options].
AB  - Malignant infantile osteopetrosis is a rare disease but can be clinically
      unequivocally diagnosed. Normal bone formation in the presence of decreased bone
      breakdown leads to the typical symptoms. The only proven curative approach, bone
      marrow transplantation, can reverse most of the symptoms and prevent progression
      to irreversible nerve damage when done early in infancy. Therefore, early
      diagnosis is decisive. We present a case report of an infant with osteopetrosis
      and discuss pathogenesis and therapeutical options.

PMID- 9561962
TI  - [Recurrent pancreatitis in pediatric ulcerative colitis--a case report].
AB  - We report on a 12 years old girl with ulcerative colitis, who after a two years
      course of her disease developed a concomitant idiopathic pancreatitis. We discuss
      the causes of acute pancreatitis in childhood in view of the presented case
      summarizing the current literature. In the literature we found only two other
      children with ulcerative colitis and idiopathic pancreatitis. Both patients were
      colectomised as our patient did. Six months after colectomy she is still free of
      symptoms.

PMID- 9561963
TI  - [Type IIB von Willebrand Jurgens syndrome as the cause of neonatal
      thrombocytopenia].
AB  - Two newborn male infants with neonatal thrombocytopenia and von Willebrand
      disease (vWD) in their family history were admitted two our hospital during the
      last two years. The second patient was later on shown to suffer from vWD type
      IIB, in the first case there was a typical history but no analysis of the
      multimeric pattern. The vWD type IIB is a rare cause for neonatal
      thrombocytopenia. Therapy with platelet concentrates alone is not in all cases
      able to correct the platelet count for more than some hours. The finding of
      (recurrent) thrombocytopenia and a familial history of vWD in a newborn infant is
      of major diagnostic value to identify cases of this rare autosomal dominant
      disease.

PMID- 9561964
TI  - [Recurrent hemorrhage from a duodenal ulcer in a 5-year-old healthy boy. A case
      report].
AB  - Peptic ulcers in infants are rare. We report a 5-year-old boy who was admitted
      with recurrent bleeding from a huge duodenal ulcer. There were no concomitant
      disease and no preceding symptoms discovered. The only clinical symptom was
      bloody stool of light red color what led to diagnostic problems. Upper
      gastrointestinal bleeding was not considered initially. Short transit time
      through the gut may suggest a bleeding source within the lower intestine.
      Gastroscopy was performed delayed. Injection therapy of the ulcer once using
      fibrin sealant was followed by definite cessation of bleeding. Helicobacter
      pylori was not found. Hormone producing tumors could be excluded. There was a
      psycho-social situation of stress recognizable for the infant. The pathogenic
      mechanism of peptic ulceration due to psycho-social stress is unknown and
      somewhat doubtful at all. Peptic ulcer disease in infants and children should
      more often be considered when dealing with diffuse abdominal pain or with
      gastrointestinal bleeding.

PMID- 9561965
TI  - Successful perioperative management of congenital cystic adenomatoid malformation
      of the lung by high frequency oscillatory ventilation--report of two cases.
AB  - BACKGROUND: Comparable to congenital diaphragmatic hernia, patients with
      congenital cystic adenomatoid malformation of the lung (CCAM) may develop life
      threatening mediastinal shift and persistent pulmonary hypertension. In patients
      with diaphragmatic hernia, high frequency oscillatory ventilation (HFOV) has been
      shown to allow perioperative stabilisation. PATIENTS: One term and one premature
      newborn of 30 gestational weeks with CCAM. Both patients developed massive
      mediastinal shift and intermittend pulmonary hypertension. METHOD: Retrospective
      chart review. RESULTS: In both patients perioperative stabilisation could be
      achieved by institution of HFOV. This allowed safe operation in the almost
      immobile surgical site and controlled transient episodes of pulmonary
      hypertension. The resection of the malformed lobe was performed under continued
      HFOV on the neonatal intensive care unit. Hereby, transport stress and additional
      hyperinflation by hand ventilation could be avoided. CONCLUSION: Comparable with
      the situation when repairing a congenital diaphragmatic hernia, perioperative
      HFOV may be advantageous in managing severe CCAM.

PMID- 9561966
TI  - Pharmacokinetics of benzo[a]pyrene in the rat.
AB  - Groups of 4 male Wistar rats were dosed intravenously with 14C-labeled
      benzo[a]pyrene dissolved in an Emulphor/water vehicle at 3 different dose levels
      and killed at 1 of 15 specific time intervals from 5 min to 32 h after dosing.
      14C-Radiolabel concentration-time data were obtained for blood, brain, adipose,
      heart, kidney, liver, lung, spleen, and testes. Benzo[a]pyrene concentration-time
      data were obtained for blood, adipose, kidney, liver, and lung. Appropriate
      mathematical models were fitted to these data and to the data for metabolites
      derived as the residuals from 14C-radiolabel minus benzo[a]pyrene difference,
      where applicable. Nonlinear kinetics were found for 14C-radiolabel in liver,
      while the data from lung for both 14C-radiolabel and for benzo[a]pyrene per se
      supported the binding of benzo[a]pyrene in that tissue.

PMID- 9561967
TI  - Comparative presynaptic neurochemical changes in rat striatum following exposure
      to chlorpyrifos or parathion.
AB  - Organophosphorus pesticides (OPs) exert acute toxicity through inhibition of
      acetylcholinesterase (AChE) in target tissues. Previous studies in our laboratory
      have demonstrated, however, that dosages of the OPs chlorpyrifos (CPF) or
      parathion (PS), which cause similar degrees of brain AChE inhibition in adult
      male rats, can produce marked differences in toxicity. While compensatory changes
      in postsynaptic receptors can modulate the clinical expression of AChE inhibition
      and lead to tolerance to these toxicants, we propose that OP-selective changes in
      presynaptic cholinergic processes can also regulate the ultimate consequences of
      AChE inhibition. The relative effects of either vehicle (peanut oil, 2 ml/kg,
      sc), CPF (280 mg/kg), or PS (6.6 mg/kg) on clinical signs of toxicity and AChE
      activity, high-affinity choline uptake (HACU), and potassium-evoked acetylcholine
      (ACh) release in striatum were examined for a 7-d period after exposure in adult
      female Sprague-Dawley rats. In vitro effects of CPF-oxon or paraoxon, the active
      oxidative metabolites of CPF and PS, on HACU were also examined in comparison
      with the prototype inhibitor hemicholinium-3 (HC-3). Similar to our previous
      findings in male rats, female rats treated with dosages of CPF or PS causing
      similar maximal degrees of AChE inhibition (82-96%) exhibited marked differences
      in response; that is, PS produced more extensive signs of acute toxicity
      (salivation, lacrimation, urination and/or defecation, i.e., SLUD signs and
      involuntary movements). CPF reduced striatal synaptosomal HACU at 1, 2, and 7 d
      after exposure, whereas PS only decreased HACU at 2 d posttreatment. While CPF
      oxon was a weak inhibitor of HACU (IC50 > 200 microM), paraoxon had no effect on
      this process in vitro. Potassium-evoked ACh release in the presence of
      physostigmine (20 microM) was not affected by either OP at 1 d but was increased
      2 d after either CPF or PS treatment and remained elevated at 7 d after exposure
      in CPF-treated rats only. ACh release in the presence of both physostigmine and
      the muscarinic antagonist atropine (1 microM) was decreased by both OPs as early
      as 1 d after exposure and remained lower at 2 d posttreatment. By 7 d, however,
      ACh release in response to atropine was decreased in CPF-treated animals only,
      suggesting that both CPF and PS affected muscarinic autoreceptor function but
      with somewhat different time courses. These results suggest that different OPs
      may selectively modify presynaptic cholinergic processes and that early, OP
      selective changes in HACU/ACh synthesis may contribute to the differential
      toxicity noted following extensive AChE inhibition by either CPF or PS.

PMID- 9561969
TI  - Assessment of the skin sensitization potential of topical medicaments using the
      local lymph node assay: an interlaboratory evaluation.
AB  - The murine local lymph node assay (LLNA) is a method for the predictive
      identification of chemicals that have a potential to cause skin sensitization.
      Activity is measured as a function of lymph node cell (LNC) proliferative
      responses stimulated by topical application of test chemicals. Those chemicals
      that induce a threefold or greater increase in LNC proliferation compared with
      concurrent vehicle controls are classified as skin sensitizers. In the present
      investigations we have evaluated further the reliability and accuracy of the
      LLNA. In the context of an international interlaboratory trial the sensitization
      potentials of six materials with a history of use in topical medicaments have
      been evaluated: benzoyl peroxide, hydroquinone, penicillin G, streptomycin
      sulfate, ethylenediamine dihydrochloride, and methyl salicylate. Each chemical
      was analyzed in the LLNA by all five laboratories. Either the standard LLNA
      protocol or minor modifications of it were used. Benzoyl peroxide and
      hydroquinone, both human contact allergens, elicited strong LLNA responses in
      each laboratory. Penicillin G, another material shown previously to cause
      allergic contact dermatitis in humans, was also positive in all laboratories.
      Streptomycin sulfate induced equivocal responses, in that this material provoked
      a positive LLNA response in only one of the five laboratories, and then only at
      the highest concentration tested. Ethylenediamine dihydrochloride dissolved in a
      3:1 mixture of acetone with water, or in 4:1 acetone:olive oil (one laboratory),
      was uniformly negative. However, limited further testing with the free base of
      ethylene diamine yielded a positive LLNA response when applied in acetone:olive
      oil (AOO). Finally, methyl salicylate, a nonsensitizing skin irritant, was
      negative at all test concentrations in each laboratory. Collectively these data
      serve to confirm that the local lymph node assay is sufficiently robust to yield
      equivalent results when performed independently in separate laboratories and
      indicate also that the LLNA is of value in assessing the skin sensitization
      potential of topical medicaments.

PMID- 9561968
TI  - Free radical activity of synthetic vitreous fibers: iron chelation inhibits
      hydroxyl radical generation by refractory ceramic fiber.
AB  - Synthetic vitreous fibers are in widespread use but the parameters that dictate
      their carcinogenicity are still a matter of scientific debate. The free radical
      activities of a panel comprising an asbestos sample and five different respirable
      synthetic vitreous fiber samples were determined, to address the hypothesis that
      carcinogenic fibers have greater free radical activity than noncarcinogenic
      fibers. On the basis of recent inhalation studies, the six samples were divided
      into three carcinogenic fibers-amphibole asbestos, silicon carbide, and
      refractory ceramic fiber 1 (designated with the abbreviation RCF 1)-and three
      noncarcinogenic fibers--man-made vitreous fiber 10 (a glass fiber sample
      designated with the abbreviation MMVF 10), Code 100/475 glass fiber, and RCF4.
      All experiments were carried out with equal fiber numbers. Of the two assays of
      free radical activity used, the plasmid assay of DNA scission showed only amosite
      asbestos to have free radical activity, while the salicylate assay of hydroxyl
      activity showed that both amosite asbestos and RCF1 release hydroxyl radicals;
      silicon carbide fibers had no free radical activity in either of the assays. None
      of the noncarcinogenic fibers demonstrated free radical activity in either of the
      assays. The differences in the two assays in demonstrating free radical activity
      with RCF1 may be due to increased release of Fe from RCF1 under the more acid
      conditions of the salicylate assay, which was confirmed by the fact that soluble
      iron caused hydroxylation of salicylate. Presence of an iron chelator inhibited
      the ability of the RCF1 fibers to cause hydroxylation of salicylate,
      demonstrating that RCF1 generates hydroxyl radical by Fenton chemical reaction in
      the same way as amphibole asbestos.

PMID- 9561970
TI  - Vertebrobasilar disease and thrombolytic treatment.

PMID- 9561971
TI  - Potential effects of common drugs on stroke recovery.
AB  - Studies in laboratory animals clearly show that the rate and extent of functional
      recovery after focal brain injury can be modulated by drugs affecting certain
      neurotransmitters in the central nervous system. Preliminary clinical studies
      suggest that similar drug effects occur in humans recovering from stroke.
      Understanding these pharmacological effects is important because several of the
      classes of drugs that impair recovery in laboratory experiments are used to treat
      coincident medical problems in patients who have had a stroke.

PMID- 9561972
TI  - Treating ischemic stroke as an emergency.
AB  - The success of treatment with tissue plasminogen activator serves as an impetus
      to approach stroke as a medical emergency; diagnosis and treatment must be
      accurate and prompt. The initial evaluation should be straightforward and aimed
      at confirming ischemic stroke as the cause of the patient's acute neurologic
      impairments. Until the usefulness of diagnostic tests to demonstrate an arterial
      occlusion is established in emergent management, their application before
      treatment should not be mandated. Most individuals with acute ischemic stroke
      will receive their initial, key treatment in a community setting. Thus,
      strategies for emergent treatment should aim at management of patients whose
      strokes are diagnosed and first treated by emergency treatment and primary care
      physicians with the collaboration of neurologists.

PMID- 9561973
TI  - Early intravenous thrombolysis with recombinant tissue-type plasminogen activator
      in vertebrobasilar ischemic stroke.
AB  - BACKGROUND: The optimal therapy of vertebrobasilar ischemic stroke is under
      debate. In the case of underlying basilar artery occlusion, intra-arterial
      thrombolysis is recommended. Because this pathologic condition is rarely found
      and the procedure is time consuming and restricted to specialized centers, the
      question arises whether early intravenous thrombolysis could also effectively be
      applied in vertebrobasilar ischemic stroke. OBJECTIVE: To determine if early
      intravenous thrombolysis could be used effectively in vertebrobasilar ischemic
      stroke. DESIGN: A case series of 12 consecutive patients with acute
      vertebrobasilar ischemia were followed up 3 months after thrombolytic treatment
      at the Department of Neurology of the University Hospital of Cologne, Cologne,
      Germany, a primary care and referral center. METHODS: Patients with clinically
      diagnosed moderate to severe vertebrobasilar ischemic stroke with clearly
      determined symptom onset were treated with intravenous recombinant tissue-type
      plasminogen activator within 3 hours after symptom onset following a protocol
      similar to that of the National Institute of Neurological Disorders and Stroke
      study. RESULTS: On admission, 7 patients exhibited moderate to severe brainstem
      symptoms without impairment of consciousness and 5 patients had impairment of
      consciousness, of whom 2 were comatose. Of 12 patients, 10 had a favorable
      outcome after 3 months defined as full independence (Barthel index score of 100)
      or return to premorbid condition. One patient had a poor outcome with complete
      dependency due to reocclusion after primarily successful thrombolysis, and 1
      patient died of severe brainstem infarction and additional space occupying
      parietal hemorrhage. CONCLUSION: Favorable outcome could be achieved in the
      majority of 12 consecutive patients with moderate to severe vertebrobasilar
      ischemic stroke treated with intravenous recombinant tissue-type plasminogen
      activator within 3 hours after symptom onset.

PMID- 9561974
TI  - Proximal extracranial vertebral artery disease in the New England Medical Center
      Posterior Circulation Registry.
AB  - OBJECTIVE: To describe the clinical features of patients with occlusive disease
      of the proximal (V1) segment of the vertebral artery. DESIGN AND PATIENTS:
      Patients with either occlusion or high-grade stenosis involving the V1 segment
      were chosen for study from the New England Medical Center Posterior Circulation
      Registry. The registry is a consecutive series of patients with signs and
      symptoms of posterior circulation ischemia seen at the New England Medical
      Center, Boston, Mass, during a 10-year period. Clinical features, radiographic
      findings, and patient outcome were reviewed. RESULTS: Of the 407 patients in the
      registry, 80 (20%) had V1 segment lesions. Patients could be classified into 5
      groups: (1) V1 disease and coexistent severe intracranial occlusive disease of
      the posterior circulation (n=22); (2) V1 disease with evidence of artery-to
      artery embolism (n=19); (3) suspected V1 disease with artery-to-artery embolism,
      but with other potential causes of stroke or less certain vascular diagnosis
      (n=20); (4) V1 disease associated with hemodynamic transient ischemic attacks
      (n=13); and (5) proximal vertebral arterial dissection (n=6). Hypertension,
      cigarette smoking, and coronary artery disease were common risk factors. Clinical
      features, location of infarct, and outcome differed between groups and reflected
      the presumed mechanisms of stroke. CONCLUSIONS: Occlusive disease involving the
      V1 segment of the vertebral artery is common in patients with posterior
      circulation ischemia, but is often associated with other potential mechanisms of
      stroke. However, in a series of patients seen at a tertiary referral center,
      occlusive disease of the V1 segment was the primary mechanism of ischemia in 9%
      of patients.

PMID- 9561975
TI  - Different predictors of neurological worsening in different causes of stroke.
AB  - OBJECTIVES: To investigate clinical determinants of neurological worsening and to
      delineate its predictors. DESIGN: Restrospective analysis of the data from the
      Lausanne Stroke Registry. PATIENTS: A total of 3038 patients with first-ever
      stroke consecutively admitted to a primary-care stroke center. MAIN OUTCOME
      MEASURES: Neurological worsening in the acute phase of stroke. RESULTS:
      Neurological worsening was observed in 38% of 300 patients with brain hemorrhage,
      34% of 1968 patients with noncardioembolic infarction, and 15% of 770 patients
      with cardioembolic infarction (P<.001). Neurological worsening was significantly
      less frequent in patients with small-artery disease than in those with large
      artery atherosclerosis or other causes. A logistic multiple regression model in
      patients with noncardioembolic infarction showed age less than 65 years,
      hypertension, lesion outside the superficial anterior circulation, absence of
      transient ischemic attack, and reduced level of consciousness as the independent
      factors in the patients with small-artery disease, while it showed involvement of
      the posterior circulation and reduced level of consciousness in the patients with
      large-artery atherosclerosis. Severe functional disability or death was more
      common in patients with neurological worsening, both in patients with large
      artery atherosclerosis and in those with small-artery disease (18% vs 9%;
      P<.001). CONCLUSIONS: Determinants of neurological worsening may include
      causative aspects rather than just the evolution of the ischemic or hemorrhagic
      process itself. For a better comprehension and treatment of neurological
      worsening, the causative and pathophysiological conditions underlying stroke
      should be differentiated as early as possible.

PMID- 9561976
TI  - Prognostic value of proton magnetic resonance spectroscopy in ischemic stroke.
AB  - OBJECTIVE: To determine the correlation between metabolite concentrations and
      clinical outcome during the acute or subacute phase of ischemic stroke by using
      single-voxel localized proton magnetic resonance spectroscopy (1H-MRS). SETTING:
      A university hospital neurologic department. PATIENTS AND METHODS: Combined
      single-voxel 1H-MRS and magnetic resonance imaging were performed on 26 patients
      with a recent ischemic stroke (on 8 patients during the first 24 hours after the
      stroke and on 18 during the first week). For all patients, the signals from N
      acetylaspartate, choline-containing compounds, and creatine-phosphocreatine were
      compared with those on the contralateral side as peak area ratios. The data for
      1H-MRS were related to scores on the Scandinavian Stroke Scale and the Barthel
      Index at a 6-month clinical follow-up. RESULTS: The signals from N
      acetylaspartate, choline-containing compounds, and creatine-phosphocreatine were
      significantly reduced in all infarcted areas (P<.001, P<.001, and P=.003,
      respectively, Wilcoxon signed rank test). A lactate signal was present in 19
      patients. The statistical analysis showed a significant positive correlation
      between N-acetylaspartate signals and Scandinavian Stroke Scale scores and
      between reduction of N-acetylaspartate signals and Barthel Index scores (Spearman
      rank correlation test). Patients in whom lactate was present had Scandinavian
      Stroke Scale scores significantly lower than patients in the group without
      lactate (Mann-Whitney U test). CONCLUSION: Single-voxel 1H-MRS performed during
      the acute or subacute phase of ischemic stroke may provide prognostic
      information.

PMID- 9561977
TI  - Magnetic resonance imaging lesion analysis in neurofibromatosis type 1.
AB  - OBJECTIVE: To define the evolution of identified high-signal brain parenchymal
      lesions on magnetic resonance imaging (MRI) studies in patients with
      neurofibromatosis type 1 (NF-1). DESIGN: A cohort of patients with NF-1 who
      underwent MRI were identified prospectively and their imaging studies analyzed.
      PATIENTS: All referred patients with NF-1 (as defined by National Institutes of
      Health consensus criteria), who had undergone imaging with MRI were eligible. Of
      123 patients with NF-1 whose conditions were evaluated, 30 patients had undergone
      59 MRIs. There were 22 males and 8 females, aged 1 to 53 years with mean age of
      12.5 years. Two groups of patients were identified, those with brain lesions
      (WBL) and those with no brain lesions. All initial and subsequently obtained MRIs
      from the WBL group were analyzed and tallied for number, size, and location of
      lesions over serial studies. RESULTS: Of the 19 patients with WBL, lesions were
      in hemispheres in 19 patients, and in the brainstem and the cerebellum in 10
      patients each, respectively. Lesions were located in the cerebellum and globus
      pallidus most often (87 of 129 lesions). Of the patients with WBL having serial
      studies, a total of 97 lesions equaling 197 units (mean, 2.03 units per lesion)
      were identified at initial study. Follow-up evaluation (interval, 0.5-4.5 years;
      mean, 2.3 years), showed a decrease in both total number of lesions (68 [-29%])
      and size (132 units; mean, 1.86 units per lesion [-33%]). Importantly, brainstem
      lesions increased in both number (+36%) and size (+6.4%) over the same intervals
      in 7 of 13 patients with WBL studied serially, whereas hemispheric and cerebellar
      lesions were more evanescent. CONCLUSIONS: High-signal T2 lesions on MRI in
      patients with NF-1 evolve over time. The evolution of the NF-1 lesion is region
      specific and may relate to preferential region-specific effects of the NF-1 gene
      product.

PMID- 9561978
TI  - Carcinoma meningitis secondary to non-small cell lung cancer: combined modality
      therapy.
AB  - BACKGROUND: Leptomeningeal metastases (LM) are increasingly diagnosed as
      anticancer therapies become more effective and result in prolonged patient
      survival. OBJECTIVE: To evaluate survival, cause of death, and treatment-related
      toxic effects in patients undergoing combined modality therapy for LM of non
      small cell lung cancer. PATIENTS AND METHODS: Thirty-two patients (age range, 48
      73 years; median, 57 years) with LM attributable to metastatic non-small cell
      lung cancer were treated prospectively. Neurologic presentation included headache
      (11 patients), cranial neuropathies (9), ataxia (5), cauda equina syndrome (3),
      myelopathy (3), meningismus (2), radiculopathy (2), and confusion (1). All
      patients underwent radiographic evaluation to determine the extent of central
      nervous system disease followed by radiotherapy (16 patients) and sequential and
      intraventricular chemotherapy (methotrexate in 32 patients; cytarabine in 16; and
      thiotepa in 6). Twelve patients received concurrent systemic chemotherapy.
      RESULTS: Central nervous system imaging demonstrated interrupted cerebrospinal
      fluid flow (13 patients), parenchymal brain metastases (9), subarachnoid nodules
      (8), hydrocephalus (5), and epidural spinal cord compression (2). Cytological
      responses were seen in 17 patients to first-line chemotherapy, 8 to second-line
      chemotherapy, and 2 to third-line chemotherapy. Treatment-related toxic effects
      included 20 patients with aseptic meningitis (grade 2 in 16; grade 3 in 4) and 12
      patients with grade 3 or 5 thrombocytopenia or neutropenia (4 related to
      intraventricular chemotherapy). Median survival was 5 months (range, 1-12
      months). Nineteen patients died of progressive LM or combined LM and systemic
      disease progression. Patients with persistent interruption of cerebrospinal fluid
      flow fared worse than patients with normal cerebrospinal fluid flow (median
      survival, 4 vs 6 months; P<.05). CONCLUSIONS: Leptomeningeal metastases in
      patients with non-small cell lung cancer may be palliated with combined modality
      therapy; however, therapy and survival is based on the extent of central nervous
      system disease present at pretreatment evaluation.

PMID- 9561979
TI  - Association between the gamma-aminobutyric acid A3 receptor gene and multiple
      sclerosis.
AB  - BACKGROUND: In a prior study we observed an association between the dopamine D2
      receptor gene (DRD2) and the age of onset and/or diagnosis of multiple sclerosis
      (MS). We hypothesized that this effect was mediated through the dopaminergic
      control of the release of prolactin, a modulator of immune response. Since gamma
      aminobutyric acid also modulates the release of prolactin, we examined the
      possible association between alleles of the GABRA3 (gamma-aminobutyric acid A3
      receptor) gene and MS. DESIGN: We examined the GABRA3 alleles of 189 subjects
      with MS who died of their disease. They were divided into test group 1 (n=64) and
      retest group 2 (n=56). Each group had a separate set of controls (group 1, n=109;
      group 2, n=430). All subjects were white. All were tested at a dinucleotide
      cytosine-adenosine repeat polymorphism with 6 alleles representing 11 to 16
      repeats. RESULTS: In the first group there was a significant difference in the
      frequency of the GABRA3 alleles (P<.002), with the most notable difference being
      an increase in the frequency of the 16-repeat allele in subjects with MS and a
      relative decrease in the other alleles. In the replication group there was again
      a significant difference in the distribution of the GABRA3 alleles (P<.001), and
      again the greatest difference was an increase in the frequency of the 16-repeat
      allele in subjects with MS. For both groups combined, a significant difference in
      the frequency of the 16-repeat allele was noted (chi2=46.30; P<.001).
      CONCLUSIONS: These results suggest the GABRA3 gene may be a risk factor for MS.
      As with the DRD2 gene, the effect may be mediated through its regulation of
      prolactin release.

PMID- 9561980
TI  - Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study.
AB  - OBJECTIVES: To evaluate in patients with multiple sclerosis (MS) the occurrence
      of clinical systemic signs and biological autoimmune abnormalities, including
      positive titers of antinuclear antibodies and antiphospholipid antibodies,
      suggestive of autoimmune diseases that may affect the central nervous system.
      Also, to compare the clinical and magnetic resonance imaging features and
      evolution of MS in patients with and without autoimmune abnormalities. DESIGN AND
      PATIENTS: Prospective study of 161 patients fulfilling the criteria of having
      probable or definite MS hospitalized in our institution between November 1990 and
      June 1992. RESULTS: Among the 161 patients, 84 (52.1%) had at least 1 clinical
      and/or biological general sign suggestive of an autoimmune disease; 64 were
      followed up for 4 to 5 years. The diagnosis of MS was confirmed in 50 patients
      and is still pending in 14 of them. No significant difference was found between
      patients with MS who were free of autoimmune features and those with autoimmune
      abnormalities (MS plus) concerning the age of disease onset, the presenting
      symptoms and signs, symptoms found on neurologic examination, and the course of
      the disease. For all patients with confirmed MS, general signs were found in
      13.3%, positive titers of antinuclear antibodies in 26%, and positive titers of
      antiphospholipid antibodies in 6.2%. CONCLUSIONS: Patients with MS with
      autoimmune features, including those with titers of antinuclear antibodies of
      1:100 or less and/or antiphospholipid antibodies, are not different than others
      with MS, and therefore should not be excluded from clinical trials.

PMID- 9561981
TI  - An analysis of extended survival in patients with amyotrophic lateral sclerosis
      treated with riluzole.
AB  - BACKGROUND: In an attempt to better understand and define the progression of
      amyotrophic lateral sclerosis (ALS), we developed a classification of 5 discrete
      health states that reflect patients' activities of daily living. These health
      states were used to determine whether patients with ALS who are treated with
      riluzole differed from those treated with placebo. SETTING: Clinics for patients
      with ALS. DESIGN: Placebo-controlled trial of riluzole treatment in 959 patients
      with ALS. INTERVENTIONS: Treatment with riluzole or placebo. MAIN DEPENDENT
      MEASURES: A Cox model was used to assess whether, from the initial randomization
      to the end of an 18-month follow-up, there was a difference in the times of
      transition into subsequent health states between patients treated with riluzole
      and those treated with placebo. RESULTS: Our analysis showed a significant
      difference in the time to transit between the riluzole and the placebo groups in
      less severely affected cases, ie, state 2 and state A (the milder states) of ALS.
      CONCLUSION: Patients receiving riluzole remained in the milder health states
      longer (P<.05).

PMID- 9561982
TI  - Platelet activation in Alzheimer disease.
AB  - BACKGROUND: In light of recent reports of diminished platelet serotonin
      concentration and increased plasma serotonin levels in patients with Alzheimer
      disease (AD), we hypothesized that a state of heightened platelet activation
      might be present in AD. OBJECTIVE: To compare baseline activation of unstimulated
      platelets in patients with AD with that in control subjects. PATIENTS AND
      METHODS: Flow cytometry was used to measure platelet activation in 91 patients
      with probable AD and 40 age-matched control subjects. Groups were compared for
      percentage of circulating platelet aggregates, expression of CD62p, formation of
      leukocyte-platelet complexes, and presence of circulating platelet
      microparticles, controlling for effects of demographic, clinical, physiological,
      and logistical factors. RESULTS: Multiple analysis of covariance on ranked data
      revealed a 39.5% increase in percentage of platelet aggregates (P=.0001), a 59.3%
      increase in expression of CD62p (P=.001), and a 53.3% increase in leukocyte
      platelet complexes (P=.0001) in the group with AD but no differences in the
      number of platelet microparticles, overall platelet count, plasma fibrinogen
      level, or plasma platelet factor 3. Activation was weakly correlated with sex,
      but was independent of age, severity of disease, duration of disease, depression,
      agitation, and family history of dementia. CONCLUSIONS: Platelets of patients
      with AD exhibit greater unstimulated activation than those of controls. Potential
      causes of such activation include possible stimulation of platelets by damaged
      cerebral endothelial cells or platelet activation induced by membrane
      abnormalities previously reported to be present in platelets of patients with AD.
      In light of recent evidence that platelets are the principal source of both
      amyloid precursor protein and beta-amyloid peptide in human blood, it is possible
      that AD platelet activation may reflect or even contribute to the pathogenesis of
      the disease.

PMID- 9561983
TI  - Behavioral disorders in Alzheimer disease: a transcultural perspective.
AB  - OBJECTIVES: To compare 2 samples of patients with Alzheimer disease (AD), from
      Italy and the United States, in order to determine transcultural differences in
      the manifestation of noncognitive symptoms. To analyze the concurrent validity,
      internal consistency reliability, between-rater reliability, and test-retest
      reliability of the Neuropsychiatric Inventory Scale (NPI). METHODS: The NPI was
      given to 50 Italian and 50 US patients with AD. To demonstrate the validity and
      reliability of the Italian version of the instrument, several different methods
      of analysis were used. The total score on the NPI and the score of single items
      in the different stages of the disease were compared in the 2 samples of
      patients. RESULTS: A high level of internal consistency reliability was
      confirmed, the between-rater reliability was very high, and the test-retest
      reliability was significantly correlated. Apathy was the most frequently recorded
      behavior in the Italian sample. Five of 10 NPI item scores showed a significant
      relation with the Mini-Mental State Examination scores in both samples. The
      Italian patients showed an increasing and significantly higher mean NPI total
      score at all levels of dementia severity when compared with the US patients. The
      scores on some NPI subscales, such as apathy, aberrant motor behavior,
      disinhibition, and agitation, were significant higher in Italian patients at
      different levels of severity covarying with educational level. CONCLUSIONS: These
      results indicate that NPI is a reliable instrument with which to study
      transcultural differences in the presentation of neuropsychiatric disturbances in
      patients with AD. The described similar pattern of behaviors between Italians and
      US patients with AD suggests a biological origin of the disorders. However,
      cultural influences must be taken in account when the focus of the study is on
      psychopathological aspects of dementia.

PMID- 9561984
TI  - Craniocerebral magnetic resonance imaging measurement and findings in Lesch-Nyhan
      syndrome.
AB  - OBJECTIVE: To provide the first comprehensive magnetic resonance imaging (MRI)
      assessment of brain in a series of patients with Lesch-Nyhan syndrome (LNS), with
      emphasis on basal ganglia measurements. DESIGN: Routine readings of MRI studies,
      repeated reading in random order blinded to subject diagnosis, and 3-dimensional
      volumetric measures of basal ganglia regions. SETTING: The Johns Hopkins
      Hospital, Baltimore, Md. PATIENTS: Seven patients with LNS who have hypoxanthine
      guanine phosphoribosyltransferase levels less than 1.6% and characteristic
      clinical features of the disorder, which include hyperuricemia, cognitive
      impairment, and dystonic movement disorder, were compared with 7 age-matched
      control subjects. Five of the 7 patients demonstrated self-injurious behavior.
      MRI studies were performed using general anesthesia because of the severity of
      the movement disorder. MAIN OUTCOME MEASURES: Measurement of brain regions from
      MRI-obtained images. RESULTS: Routine readings described mild cerebral atrophy in
      2 of 7 patients, but no caudate or putamen abnormalities were reported. However,
      on the directed blinded rereading, small caudates were suspected in 5 of 7 cases,
      and abnormalities in cerebral size and cranium were identified. Volumetric
      studies of the patients with LNS confirmed a 34% decrease in caudate volume
      (P<.001), a 17% decrease in total cerebral volume (P<.03), and a 12% decrease in
      putamen volume (P=.19). CONCLUSIONS: To our knowledge, this is the first
      demonstration of consistent neuroanatomic abnormalities in LNS. The findings of
      reduced basal ganglia volume are consistent with the dystonic movement disorder.

PMID- 9561986
TI  - Recovery of neglect after right hemispheric damage: H2(15)O positron emission
      tomographic activation study.
AB  - BACKGROUND: The neural correlates of recovery of unilateral neglect (ULN), as
      well as of other consequences of focal brain damage, are largely unknown.
      Functional neuroimaging methods (in particular, positron emission tomography
      [PET]) can be applied to the in vivo study of recovery mechanisms in neurologic
      patients. OBJECTIVE: To evaluate the functional cerebral correlates of recovery
      from ULN in patients with right-sided lesions, with the use of a PET activation
      paradigm. METHODS: Study of 3 patients with cerebrovascular lesions that involved
      corticosubcortical (patient 1) or subcortical (patients 2 and 3) areas of the
      right hemisphere. Unilateral neglect was tested twice, before and after
      completion of a 2-month rehabilitation program, after which all 3 patients showed
      considerable improvement. Similarly, 2 PET examinations were performed, before
      and after recovery, during the performance of a visuospatial task requiring the
      patients to detect and respond to visual targets moving on a computer screen from
      the right to the left visual hemifield (experimental condition). The cerebral
      activation was compared with a baseline task in which subjects responded to a
      black dot flashing in a fixed position of the right hemifield. RESULTS: The brain
      areas activated by the performance of the visuospatial task before and after
      recovery were compared. In all 3 patients, the regions notably more active after
      recovery were almost exclusively found in right-sided cortical areas and largely
      overlapped with those observed in a group of 4 normal subjects performing the
      same task. Other areas, which have been shown to be involved in attentional and
      oculomotor tasks in other PET studies, were also activated in patients with ULN.
      CONCLUSIONS: The behavioral recovery of ULN in these patients with predominantly
      subcortical lesions is mainly associated with cerebral activations in cortical
      regions similar to those observed in normal subjects. There is some evidence of
      functional reorganization in individual subjects, which involves other areas
      related to space representation and exploration.

PMID- 9561985
TI  - Pendular nystagmus in patients with peroxisomal assembly disorder.
AB  - BACKGROUND: Pendular nystagmus commonly occurs in congenital and acquired
      disorders of myelin. OBJECTIVE: To characterize the nystagmus in 3 siblings with
      an infantile form of an autosomal recessive peroxisomal assembly disorder causing
      leukodystrophy. DESIGN: We examined visual function and measured eye movements
      using infrared oculography. We noted changes in eye speed and frequency before
      and after the administration of gabapentin to 1 patient. RESULTS: All 3 siblings
      showed optic atrophy and pendular nystagmus that was predominantly horizontal, at
      a frequency of 3 to 6 Hz, with phase shifts of 45 degrees to 80 degrees between
      the oscillations of each eye. Gabapentin administered to 1 child caused a modest
      improvement of vision and the reduction of the velocity and frequency of
      oscillations in the eye with worse nystagmus. CONCLUSION: The pendular nystagmus
      in these patients was due to their leukodystrophy and may have a similar
      pathogenesis to the oscillations seen in other disorders affecting central
      myelin.

PMID- 9561987
TI  - Neurology was there in 1918.

PMID- 9561988
TI  - 29th Bethesda Conference. Ethics in Cardiovascular Medicine (1997). Introduction.

PMID- 9561989
TI  - Task force 1: external influences on the practice of cardiology.

PMID- 9561990
TI  - Task force 2: application of medical and surgical interventions near the end of
      life.

PMID- 9561991
TI  - Task force 3: clinical research in a molecular era and the need to expand its
      ethical imperatives.

PMID- 9561992
TI  - The sulfonylurea controversy: more questions from the heart.
AB  - Myocardial ischemia and infarction are associated with substantially increased
      morbidity and mortality among patients with diabetes mellitus. Although many
      factors contribute to the increased morbidity and mortality, in patients with non
      insulin-dependent (type II) diabetes mellitus, one contributor may be the use of
      sulfonylurea drugs, the most widely used oral hypoglycemic agents. Such a
      possibility, which first arose over a 25 years ago when it was observed that
      patients taking sulfonylurea drugs had increased cardiovascular mortality, has
      recently resurfaced after the discovery that sulfonylureas act by inhibiting
      adenosine triphosphate (ATP)-sensitive potassium channels. In the pancreas,
      inhibition of ATP-sensitive potassium channels induces release of insulin; but in
      the heart, inhibition of these channels prevents ischemic preconditioning, an
      endogenous cardioprotective mechanism that protects the heart from lethal injury.
      This review outlines the current understanding of the molecular and cellular
      pharmacodynamics of sulfonylurea drugs and discusses the potential clinical
      consequences of inhibition of ATP-sensitive potassium channels in the heart of
      diabetic patients with cardiac disease in whom the use of sulfonylureas may be
      harmful.

PMID- 9561993
TI  - Trends in the quality of care for Medicare beneficiaries admitted to the hospital
      with unstable angina.
AB  - OBJECTIVES: We sought to 1) determine the proportion of appropriate elderly
      patients admitted to the hospital with unstable angina who are treated with
      aspirin and heparin; 2) identify patient factors associated with the Agency for
      Health Care Policy and Research (AHCPR) guideline-based use of aspirin and
      heparin; and 3) compare practice patterns and patient outcomes before and after
      publication of the AHCPR guidelines. BACKGROUND: Improving the care of patients
      with unstable angina may provide immediate opportunities to mitigate the adverse
      consequences of unstable angina. However, despite the importance of this
      diagnosis, there is a paucity of information on the patterns of treatment and
      outcomes across diverse sites and recent trends in practice that have occurred,
      especially since the publication of the AHCPR practice guidelines. METHOD: We
      performed a retrospective cohort study using data created from medical charts and
      administrative files. The sample included 300 consecutive patients admitted to
      one of three Connecticut hospitals in the period 1993 to 1994 and 150 consecutive
      patients admitted in 1995 with a principal discharge diagnosis of unstable angina
      or chest pain. RESULTS: Of the 384 patients > or =65 years old who had no
      contraindications to aspirin on hospital admission, 276 (72%) received it. Of the
      369 patients > or =65 years old who had no contraindications to heparin on
      admission, 88 (24%) received it. Among the 321 patients > or =65 years old who
      had no contraindications to aspirin at hospital discharge, 208 (65%) were
      prescribed it. When 1995 was compared with 1993 to 1994, the use of aspirin (odds
      ratio [OR] 2.3, 95% confidence interval [CI] 1.3 to 4.0) and heparin (OR 2.8, 95%
      CI 1.6 to 4.9) on hospital admission significantly increased, and the use of
      aspirin at discharge (OR 1.4, 95% CI 0.8 to 2.4) increased. Concomitantly, there
      was a significant reduction in 30-day readmission (OR 0.52, 95% CI 0.27 to 0.99).
      CONCLUSIONS: Our results indicate an improvement in the care and outcomes of
      elderly patients with unstable angina, but there remain opportunities for further
      improvement.

PMID- 9561994
TI  - Heparin for acute myocardial infarction: the controversy continues.

PMID- 9561996
TI  - Use and effectiveness of intravenous heparin therapy for treatment of acute
      myocardial infarction in the elderly.
AB  - OBJECTIVES: We sought to determine the use and association with 30-day mortality
      of intravenous heparin for the treatment of acute myocardial infarction in
      elderly patients not treated with a reperfusion strategy and without
      contraindications to anticoagulation. BACKGROUND: The benefit of using full-dose
      intravenous heparin for the treatment of acute myocardial infarction in the
      elderly is not known. METHODS: We conducted a retrospective cohort study using
      hospital medical records of all Medicare beneficiaries admitted to the hospital
      with an acute myocardial infarction in Alabama, Connecticut, Iowa and Wisconsin
      from June 1992 through February 1993. RESULTS: Among the 6,935 patients > or = 65
      years old who had no absolute chart-documented contraindications to heparin,
      3,227 (47%) received early full-dose intravenous heparin therapy. After
      adjustment for baseline differences in demographic, clinical and treatment
      factors between patients with and without heparin, the use of heparin (odds ratio
      1.02, 95% confidence interval 0.87 to 1.18) was not associated with a
      significantly better 30-day mortality rate. CONCLUSIONS: Although intravenous
      heparin was commonly used for treatment of acute myocardial infarction in the
      elderly, it was not associated with an improved 30-day mortality rate. Although
      the findings of this observational study must be interpreted with care, they lead
      us to question whether the prevalent use of intravenous heparin has therapeutic
      effectiveness in this population.

PMID- 9561995
TI  - Safety and cost-effectiveness of early discharge after primary angioplasty in low
      risk patients with acute myocardial infarction. PAMI-II Investigators. Primary
      Angioplasty in Myocardial Infarction.
AB  - OBJECTIVES: The second Primary Angioplasty in Myocardial Infarction (PAMI-II)
      study evaluated the hypothesis that primary percutaneous transluminal coronary
      angioplasty (PTCA), with subsequent discharge from the hospital 3 days later, is
      safe and cost-effective in low risk patients. BACKGROUND: In low risk patients
      with myocardial infarction (MI), few data exist regarding the need for intensive
      care and noninvasive testing or the appropriate length of hospital stay. METHODS:
      Patients with acute MI underwent emergency catheterization with primary PTCA when
      appropriate. Low risk patients (age <70 years, left ventricular ejection fraction
      >45%, one- or two-vessel disease, successful PTCA, no persistent arrhythmias)
      were randomized to receive accelerated care (admission to a nonintensive care
      unit and day 3 hospital discharge without noninvasive testing [n = 237] or
      traditional care [n = 234]). RESULTS: Patients who received accelerated care had
      similar in-hospital outcomes but were discharged 3 days earlier (4.2+/-2.3 vs.
      7.1+/-4.7 days, p = 0.0001) and had lower hospital costs ($9,658+/-5,287 vs.
      $11,604+/-6,125 p = 0.002) than the patients who received traditional care. At 6
      months, accelerated and traditional care groups had a similar rate of mortality
      (0.8% vs. 0.4%, p = 1.00), unstable ischemia (10.1% vs. 12.0%, p = 0.52),
      reinfarction (0.8% vs. 0.4%, p = 1.00), stroke (0.4% vs. 2.6%, p = 0.07),
      congestive heart failure (4.6% vs. 4.3%, p = 0.85) or their combined occurrence
      (15.2% vs. 17.5%, p = 0.49). The study was designed to detect a 10% difference in
      event rates; at 6 months, only a 2.3% difference was measured between groups,
      indicating an actual power of 0.19. CONCLUSIONS: Early identification of low risk
      patients with MI allowed safe omission of the intensive care phase and
      noninvasive testing, and a day 3 hospital discharge strategy, resulting in
      substantial cost savings.

PMID- 9561997
TI  - Low plasma ascorbic acid independently predicts the presence of an unstable
      coronary syndrome.
AB  - OBJECTIVES: This study sought to investigate the relations between plasma
      antioxidant status, extent of atherosclerosis and activity of coronary artery
      disease. BACKGROUND: Previous studies indicate that increased antioxidant intake
      is associated with decreased coronary disease risk, but the underlying mechanisms
      remain controversial. METHODS: Plasma samples were obtained from 149 patients
      undergoing cardiac catheterization (65 with stable angina, 84 with unstable
      angina or a myocardial infarction within 2 weeks). Twelve plasma
      antioxidant/oxidant markers were measured and correlated with the extent of
      atherosclerosis and the presence of an unstable coronary syndrome. RESULTS: By
      multiple linear regression analysis, age (p < 0.001), diabetes mellitus (p <
      0.001), male gender (p < 0.001) and hypercholesterolemia (p = 0.02) were
      independent predictors of the extent of atherosclerosis. No antioxidant/oxidant
      marker correlated with the extent of atherosclerosis. However, lower plasma
      ascorbic acid concentration predicted the presence of an unstable coronary
      syndrome by multiple logistic regression (odds ratio [OR] 0.59, 95% confidence
      interval [CI] 0.40 to 0.89, p = 0.01). The severity of atherosclerosis also
      predicted the presence of an unstable coronary syndrome (OR 1.7, 95% CI 1.14 to
      2.47, p = 0.008) when all patients were considered. When only patients with
      significant coronary disease were considered (at least one stenosis >50%),
      ascorbic acid concentration (OR 0.56, 95% CI 0.37 to 0.85, p = 0.008) and total
      plasma thiols (OR 0.52, 95% CI 0.34 to 0.80, p = 0.004) predicted the presence of
      an unstable coronary syndrome, whereas the extent of atherosclerosis did not.
      CONCLUSIONS: These data are consistent with the hypothesis that the beneficial
      effects of antioxidants in coronary artery disease may result, in part, by an
      influence on lesion activity rather than a reduction in the overall extent of
      fixed disease.

PMID- 9561998
TI  - Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is
      associated with coronary artery plaque calcification as assessed by intravascular
      ultrasound.
AB  - OBJECTIVES: We evaluated the influence of the insertion/deletion (I/D)
      polymorphism of the angiotensin I-converting enzyme (ACE) gene on coronary plaque
      morphology and calcification in patients with angiographically documented
      coronary artery disease (CAD). BACKGROUND: The ACE I/D polymorphism has been
      associated with an increased risk of myocardial infarction in patients with the
      DD genotype but not with the presence of native CAD. METHODS: We studied 146
      patients undergoing percutaneous transluminal coronary angioplasty for stable
      angina pectoris by means of preinterventional intravascular ultrasound (IVUS).
      Qualitative and quantitative criteria were used to classify the target lesions as
      poorly or highly echoreflective or as calcified. Genomic deoxyribonucleic acid
      was analyzed by polymerase chain reaction (PCR) to identify the I/D polymorphism,
      with a second insertion-specific PCR in DD genotypes to prevent mistyping.
      RESULTS: The ACE genotype groups (DD 46, ID 68, II 32) were well matched for the
      basic characteristics. Patients with the DD genotype had significantly more
      calcified lesions (DD 80%, ID 57%, II 66%; unadjusted odds ratio [OR] 2.88, 95%
      confidence interval [CI] 1.30 to 6.92, p = 0.008) and more calcifications >180
      degrees of the vessel circumference (DD 22%, ID 10%, II 6%; OR 2.80, 95% CI 1.05
      to 7.63, p = 0.03). The prevalence of myocardial infarction was not significantly
      associated with coronary calcification (OR 1.44, 95% CI 0.72 to 2.88, p = 0.31).
      CONCLUSIONS: Patients with CAD and the ACE DD genotype have a significantly
      higher incidence and greater extent of coronary lesion calcification, as
      determined by IVUS. This finding indicates that the ACE I/D gene polymorphism is
      related to the development or progression of atherosclerotic plaque
      calcification.

PMID- 9561999
TI  - Postischemic left ventricular dysfunction is abolished by alpha-adrenergic
      blocking agents.
AB  - OBJECTIVES: We sought to evaluate the efficacy of alpha-adrenergic blocking
      agents in counteracting left ventricular (LV) dysfunction occurring after
      transient ischemia in humans. BACKGROUND: The mechanisms underlying postischemic
      LV dysfunction are largely unknown. METHODS: Percutaneous transluminal coronary
      angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50
      patients undergoing coronary stenting for 77+/-5% stenosis, LV function was
      monitored by transesophageal echocardiography during and 30-min after PTCA.
      Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of
      the alpha-blocker phentolamine intracoronarily, 15 patients received 600
      microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the
      combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10
      patients received saline. RESULTS: Fifteen minutes after successful coronary
      dilation, significant contractile dysfunction occurred in previously ischemic and
      nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary
      resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV
      dysfunction and coronary resistance and the increase in vasoconstriction.
      Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8%
      and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol
      combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in
      control subjects. CONCLUSIONS: LV dysfunction occurs after PTCA, as described in
      animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and
      microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by
      combining alpha- and beta-blockers. The evidence of diffuse rather than regional
      dysfunction, together with the opposite effects of alpha- and beta-blockade,
      supports the hypothesis of neural mechanisms eliciting postischemic LV
      dysfunction.

PMID- 9562000
TI  - Biphasic response to dobutamine predicts improvement of global left ventricular
      function after surgical revascularization in patients with stable coronary artery
      disease: implications of time course of recovery on diagnostic accuracy.
AB  - OBJECTIVES: This study sought to evaluate the time course of improvement of left
      ventricular (LV) dysfunction in stable patients and its implications on the
      accuracy of dobutamine echocardiography for predicting improvement after surgical
      revascularization. BACKGROUND: Little is known about the optimal timing for
      evaluation of postrevascularization recovery of the contractile function of
      viable myocardium. METHODS: Sixty-one patients with chronic ischemic LV
      dysfunction scheduled for elective surgical revascularization were prospectively
      selected. They underwent dobutamine echocardiography (5 to 40 microg/kg body
      weight per min) and radionuclide ventriculography both preoperatively and at 3
      month follow-up. At 14 months, another evaluation of LV function was obtained. To
      analyze echocardiograms, a 16-segment model and a five-point scoring system were
      used. Dyssynergic segments were considered likely to recover in the presence of a
      biphasic contractile response to dobutamine. Improvement of global function was
      defined as a > or =5% increase in LV ejection fraction (LVEF). RESULTS: Of the 61
      patients, LVEF improved in 12 at 3 months and in 19 at late follow-up (from 32+/
      8% to 42+/-9%, p < 0.0001). The frequency and time course of improvement of LVEF
      were similar in patients with mild and severe LV dysfunction. A biphasic
      response, identified in 186 of the 537 dyssynergic segments, was predictive of
      recovery in 63% at 3 months and in 75% at late follow-up. The positive predictive
      value was best in the most severe dyssynergic segments (90% vs. 67%). Other
      responses were highly predictive for nonrecovery (92%). The sensitivity and
      specificity for improvement of global function on a patient basis (> or =4
      biphasic segments) were 89% and 81%, respectively, at late follow-up.
      CONCLUSIONS: Serial postoperative follow-up studies demonstrate incomplete
      recovery of contractile function at 3 months. The diagnostic accuracy of
      dobutamine echocardiography for predicting recovery is dependent on three
      factors: the combining of low and high dobutamine dosages, the severity of
      regional dyssynergy and the timing of evaluation.

PMID- 9562001
TI  - Clinical value of acute rest technetium-99m tetrofosmin tomographic myocardial
      perfusion imaging in patients with acute chest pain and nondiagnostic
      electrocardiograms.
AB  - OBJECTIVES: We sought to evaluate the clinical use and cost-analysis of acute
      rest technetium-99m (Tc-99m) tetrofosmin single-photon emission computed
      tomographic (SPECT) myocardial perfusion imaging in patients with chest pain and
      a normal electrocardiogram (ECG). BACKGROUND: Current approaches used in
      emergency departments (EDs) for treating patients presenting with chest pain and
      a nondiagnostic ECG result in poor resource utilization. METHODS: Three hundred
      fifty-seven patients presenting to six centers with symptoms suggestive of
      myocardial ischemia and a nondiagnostic ECG underwent Tc-99m tetrofosmin SPECT
      during or within 6 h of symptoms. Follow-up evaluation was performed during the
      hospital period and 30 days after discharge. All entry ECGs, SPECT images and
      cardiac events were reviewed in blinded manner and were not available to the
      admitting physicians. RESULTS: By consensus interpretation, 204 images (57%) were
      normal, and 153 were abnormal (43%). Of 20 patients (6%) with an acute myocardial
      infarction (MI) during the hospital period, 18 had abnormal images (sensitivity
      90%), whereas only 2 had normal images (negative predictive value 99%). Multiple
      logistic regression analysis demonstrated abnormal SPECT imaging to be the best
      predictor of MI and significantly better than clinical data. Using a normal SPECT
      image as a criterion not to admit patients would result in a 57% reduction in
      hospital admissions, with a mean cost savings per patient of $4,258. CONCLUSIONS:
      Abnormal rest Tc-99m tetrofosmin SPECT imaging accurately predicts acute MI in
      patients with symptoms and a nondiagnostic ECG, whereas a normal study is
      associated with a very low cardiac event rate. The use of acute rest SPECT
      imaging in the ED can substantially and safely reduce the number of unnecessary
      hospital admissions.

PMID- 9562002
TI  - Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and
      impairs recovery of function after revascularization.
AB  - OBJECTIVES: We sought to define the effects of time on contractile function,
      morphology and functional recovery after coronary revascularization in patients
      with dysfunctional but viable (hibernating) myocardium. BACKGROUND: Functional
      recovery after coronary artery bypass graft surgery in patients with chronic
      myocardial hibernation is incomplete or delayed. The proposed cause is a
      progressive temporal degeneration of cardiomyocytes. METHODS: In 32 patients with
      multivessel coronary disease, regional wall motion analysis was performed in
      hypoperfused but metabolically active areas before and 6 months after bypass
      surgery. During bypass surgery, transmural biopsy samples were obtained from the
      center of the hypokinetic zone for light and electron microscopic analyses. The
      proposed duration of myocardial hibernation was retrospectively assessed.
      RESULTS: Patients with a subacute hibernating condition (<50 days) demonstrated a
      higher preoperative ejection fraction (EF, 50+/-8%), and a better preserved wall
      motion (WM) in the supraapical wall (-1.4+/-0.4) than did patients with
      intermediate-term (>50 days, EF 37+/-9%, p < 0.05; WM -2.4+/-1.5, p = 0.08) or
      chronic (>6 months, EF 40+/-14%, WM -2.7+/-0.9, p < 0.005) ischemia. Structural
      degeneration correlated with the duration of ischemia (r = 0.56, p < 0.05).
      Postoperative recovery of function was enhanced in patients with a short history
      of hibernation compared with patients with an intermediate-term or chronic
      condition (EF 60+/-10% vs. 40+/-10%, p < 0.001, and vs. 47+/-14%, p < 0.05).
      CONCLUSIONS: Hibernating myocardium exhibits time-dependent deterioration due to
      progressive structural degeneration with enhanced fibrosis. Early
      revascularization should be attempted to salvage the jeopardized tissue and
      improve postoperative outcome.

PMID- 9562003
TI  - Low dose dobutamine echocardiography predicts improvement in functional capacity
      after exercise training in patients with ischemic cardiomyopathy: prognostic
      implication.
AB  - OBJECTIVES: This study sought to investigate whether the identification of
      hibernating myocardium by low dose dobutamine stress echocardiography (LDSE) may
      predict an improvement in functional capacity after moderate exercise training in
      patients with ischemic cardiomyopathy. Another objective was to assess whether
      exercise training may affect the outcome. BACKGROUND: There is evidence that
      exercise training improves left ventricular (LV) function as well as functional
      capacity in patients with a previous myocardial infarction and LV dysfunction. We
      hypothesized that the magnitude of these improvements might be related to the
      extent of hibernating myocardium. METHODS: We studied 71 consecutive patients
      56+/-9 years old (mean +/- SD) with chronic heart failure secondary to ischemic
      cardiomyopathy (LV ejection fraction [LVEF] <40%). All patients were in sinus
      rhythm and were clinically stable during the previous 3 months. Patients were
      randomized into two matched groups. Group T (n = 36) underwent exercise training
      at 60% of peak oxygen uptake (Vo2) three times a week for 10 weeks. Group C (n =
      35) did not exercise. At study entry and end, all patients underwent an exercise
      test with gas exchange analysis and LDSE (5 to 20 microg/kg body weight per min).
      RESULTS: At baseline, a positive contractile response (CS+) to LDSE was observed
      in 317 of 576 segments in group T and 291 of 560 segments in group C. After 10
      weeks, peak Vo2 and peak work rate increased only in trained patients (peak Vo2:
      from 16.2+/-3 to 20.8+/-4 ml/kg per min; work capacity: from 108+/-20 to 131+/-25
      W, p < 0.001 vs. group C for both). The presence of CS+ at baseline was
      associated with a sensitivity of 70% and a specificity of 77% for predicting an
      increase in the functional capacity after exercise training. Positive and
      negative predictive values of LDSE were 84% and 59%, respectively. Independent
      predictors of cardiac events were a pre-to-posttraining difference in LVEF at
      peak dobutamine infusion and the presence of a viable response at baseline (p =
      0.004 and 0.008, respectively). The log-rank test demonstrated that trained
      patients had a significantly lower probability of cardiac events during follow-up
      than sedentary control patients (p < 0.001). CONCLUSIONS: The presence of
      hibernating myocardium as assessed by LDSE predicts the magnitude of improvement
      in functional capacity after moderate exercise training in patients with chronic
      heart failure. A significant increase in functional capacity after exercise
      training is associated with a lower incidence of cardiac events during follow-up.

PMID- 9562004
TI  - Transient ischemia does not limit subsequent ischemic regional dysfunction in
      humans: a transesophageal echocardiographic study during minimally invasive
      coronary artery bypass surgery.
AB  - OBJECTIVES: This study sought to assess the effects of sequential coronary artery
      occlusion during minimally invasive coronary artery bypass graft surgery (CABG)
      on hemodynamic variables and left ventricular systolic function by means of
      transesophageal echocardiography (TEE). BACKGROUND: Clinical and experimental
      studies suggest a protective effect of ischemic preconditioning in patients with
      acute coronary syndromes. However, the effect of repetitive myocardial ischemia
      on myocardial mechanical function in humans is not completely understood.
      METHODS: Seventeen patients with left anterior descending coronary artery (LAD)
      stenosis > or =70% and normal rest left ventricular systolic function referred
      for minimally invasive CABG underwent intraoperative TEE for assessment of
      regional left ventricular wall motion and measurement of hemodynamic variables at
      baseline (baseline 1), during a 5-min coronary occlusion (occlusion 1), after a 5
      min reperfusion period (baseline 2) and a during a second coronary occlusion
      during bypass anastomosis (occlusion 2). RESULTS: Left ventricular wall motion
      score (LVWMS) increased significantly from baseline (16.0) to occlusion 1 (21.4+/
      3.1 [mean +/- SD], p < 0.05) and occlusion 2 (21.8+/-3.1, p < 0.05). No
      difference in LVWMS was noted between occlusions 1 and 2. Pulmonary artery
      systolic pressure increased significantly from baseline (25+/-6 mm Hg) to
      occlusion 1 (32+/-7 mm Hg, p < 0.05) and occlusion 2 (33+/-6 mm Hg, p < 0.05).
      Pulmonary artery diastolic pressure also increased significantly from baseline
      (12+/-4 mm Hg) to occlusion 1 (16+/-4 mm Hg, p < 0.05) and occlusion 2 (16+/-4 mm
      Hg, p < 0.05). No significant differences in pulmonary artery pressures were
      noted between occlusions 1 and 2. CONCLUSIONS: Ischemic dysfunction was
      precipitated by the 5-min LAD occlusion, as shown by the increase in LVWMS and
      pulmonary artery pressure. However, a 5-min coronary occlusion and the resulting
      ischemia do not alter regional left ventricular systolic function during
      subsequent ischemia in humans.

PMID- 9562005
TI  - Dobutamine magnetic resonance imaging predicts contractile recovery of
      chronically dysfunctional myocardium after successful revascularization.
AB  - OBJECTIVES: This study sought to evaluate whether myocardial viability, as
      assessed by magnetic resonance imaging (MRI), reliably predicts
      postrevascularization left ventricular (LV) recovery. BACKGROUND: Compared with
      positron emission tomographic findings, MRI has proved to be a reliable technique
      for the identification of residual myocardial viability. However, the predictive
      accuracy of MRI-assessed preserved end-diastolic wall thickness (DWT) and
      dobutamine-induced systolic wall thickening (SWT) for LV functional recovery has
      not yet been evaluated. METHODS: Rest and low dose dobutamine MRI was performed
      in 43 patients with a chronic infarct (> or =4 months since ischemic event) and
      LV dysfunction who had undergone revascularization of the infarct-related vessel.
      On the basis of segmental evaluation of corresponding short-axis tomograms,
      infarct regions were graded viable by MRI if 1) DWT was > or =5.5 mm, and 2)
      dobutamine-induced SWT was > or =2 mm in > or =50% of dysfunctional segments
      related to the infarct region. Functional recovery was defined as SWT > or =2 mm
      in > or =50% of infarct-related segments at rest 4 to 6 months after successful
      revascularization. RESULTS: Recovery of regional SWT could be observed in 27
      (63%) of 43 patients. Comparison MRI grading before and after revascularization
      indicated that dobutamine-induced SWT was a better predictor of LV functional
      recovery (sensitivity 89%, specificity 94%) than was preserved DWT (sensitivity
      92%, specificity 56%). Segments that remained akinetic after revascularization
      had significantly lower DWT (6.0+/-3.1 mm [n = 219] vs. 9.8+/-2.6 mm [n = 188], p
      < 0.001) than those with improved SWT. Left ventricular ejection fraction
      increased significantly in patients with dobutamine-induced SWT than in those
      with no contractile reserve (14+/-9% vs. 3+/-9%, p < 0.0002), and the magnitude
      of this increase was correlated with the number of dobutamine-responsive segments
      per infarct region (r = 0.68, p < 0.0001). CONCLUSIONS: Quantitative assessment
      of dobutamine-induced SWT in chronic infarcts by MRI is a highly accurate
      predictor of LV functional recovery, and the presence of significantly reduced
      DWT reliably indicates irreversible myocardial damage. Therefore, dobutamine
      stress testing for the assessment of myocardial viability can be restricted to
      patients with preserved DWT.

PMID- 9562006
TI  - Flow dynamics of angiographically no-flow patent internal mammary artery grafts.
AB  - OBJECTIVES: This study sought to assess the flow dynamics of internal mammary
      artery grafts (IMAGs) in no-flow situations by use of a Doppler guide wire.
      BACKGROUND: Functionally no-flow and anatomically patent IMAGs have been reported
      by angiography in patients with a patent recipient coronary artery. METHODS: The
      study included 12 patients with an IMAG to the left anterior descending coronary
      artery (LAD) in whom no-flow patency of the graft was suspected angiographically.
      Thirteen patients with a normally functioning IMAG whose LAD was occluded in the
      proximal portion and was supplied only from the graft served as control patients.
      Phasic flow velocities were recorded in the distal portion of the graft and the
      recipient LAD using a 0.014-in., 15-MHz Doppler guide wire at rest and during
      hyperemia (0.14-mg/kg body weight per min intravenous adenosine infusion).
      RESULTS: There were no significant differences in systolic (15+/-3 vs. 19+/-6
      cm/s, p = NS), diastolic (35+/-11 vs. 37+/-7 cm/s, p = NS) and time-averaged peak
      velocities at rest (20+/-5 vs. 21+/-5 cm/s, p = NS), during hyperemia (51+/-12
      vs. 54+/-8 cm/s, p = NS) and in coronary flow velocity reserve (2.8+/-0.9 vs.
      2.7+/-0.3, NS) in the native LAD in patients with a no-flow patent graft versus
      control patients. Within the graft, to and fro signals with systolic reversal and
      diastolic anterograde flow were seen in the no-flow patent grafts, although
      anterograde flow signals were recorded in systole and diastole in control
      patients. Systolic (-28+/-19 vs. 22+/-9 cm/s, p < 0.01), diastolic (18+/-17 vs.
      44+/-14 cm/s, p < 0.01) and time-averaged (-2+/-6 vs. 26+/-9 cm/s, p < 0.01) peak
      velocities at rest were significantly smaller in the no-flow patent grafts than
      in control grafts. During hyperemia, anterograde flow became predominant, with a
      reduction in retrograde systolic flow signal and an increase in diastolic flow
      velocity and time-averaged peak velocity in the no-flow patent grafts, and no
      flow situations disappeared temporarily. CONCLUSIONS: Functionally no-flow
      situations of IMAGs manifesting to and fro signals with systolic flow reversal
      and diastolic antegrade low flow velocity are temporary conditions in certain
      hemodynamic circumstances, and these grafts function as conduits during hyperemic
      states.

PMID- 9562007
TI  - Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in
      acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and
      one-year follow-up.
AB  - OBJECTIVES: This study sought to compare the efficacy of 2-h regimens of
      alteplase and streptokinase in acute massive pulmonary embolism. The primary end
      point was immediate hemodynamic improvement, and secondary end points included
      early clinical efficacy and safety, as well as 1-year clinical outcome.
      BACKGROUND: Several thrombolytic regimens have been compared for the past 10
      years in randomized studies, showing that 2-h infusion regimens of alteplase or
      urokinase lead to faster hemodynamic improvement than former 12- to 24-h
      administration protocols in acute massive pulmonary embolism. Many trials have
      focused on immediate hemodynamic and angiographic outcomes, but none has
      addressed long-term follow-up after thrombolysis. METHODS: Sixty-six patients
      with acute massive pulmonary embolism (Miller score > 17 and mean pulmonary
      artery pressure >20 mm Hg) were randomly assigned to receive either a 100-mg 2-h
      infusion of alteplase (n = 23) or 1.5 million IU of streptokinase over 2 h (n =
      43). In both groups, heparin infusion was started at the end of thrombolytic
      infusion and adapted thereafter. Total pulmonary resistance was monitored over a
      12-h period. Pulmonary vascular obstruction was assessed 36 to 48 h after
      thrombolytic therapy. One-year follow-up information included death, cause of
      death, recurrent pulmonary embolism, chronic thromboembolic pulmonary
      hypertension, stroke and bleeding. RESULTS: Both groups had similar baseline
      angiographic and hemodynamic characteristics of severity, with maintained cardiac
      output in 64 (97%) of 66 patients. The results (mean +/- SD) demonstrated that
      despite a faster total pulmonary resistance improvement observed at 1 h in the
      alteplase group compared with the streptokinase group (33+/-16% vs. 19 16%, p =
      0.006), a similar hemodynamic efficacy was obtained at 2 h when both thrombolytic
      regimens were completed (38+/-18% vs. 31+/-19%). There was no significant
      difference in either pulmonary vascular obstruction at 36 to 48 h or bleeding
      complication rates. One-year event-free survival was similar in both groups, as
      most events were related to concomitant diseases. CONCLUSIONS: These results
      suggest that a 2-h regimen of streptokinase can be routinely used in patients
      with massive pulmonary embolism and maintained cardiac output without obviously
      compromising efficacy or safety.

PMID- 9562008
TI  - Regression of radial artery wall hypertrophy and improvement of carotid artery
      compliance after long-term antihypertensive treatment in elderly patients.
AB  - OBJECTIVES: The present study was designed to assess whether a diuretic- or an
      angiotensin-converting enzyme inhibitor-based treatment can reduce arterial wall
      hypertrophy of a distal muscular medium-sized artery--the radial artery--and the
      stiffness of a proximal large elastic artery--the common carotid artery.
      BACKGROUND: Large-artery wall thickness and stiffness are increased during
      sustained essential hypertension and contribute to the increased risk of
      complications. Whether antihypertensive treatment can normalize the wall
      hypertrophy of conducting arteries has not yet been determined. METHODS: Seventy
      seven elderly hypertensive patients were randomized to receive 9 months of double
      blind treatment with perindopril (2 to 8 mg/day) or the diuretic combination of
      hydrochlorothiazide (12.5 to 50 mg/day) plus amiloride (1.25 to 5 mg/day) after a
      1-month placebo washout period. If systolic blood pressure remained at >160 mm Hg
      after 5 months, chlorthalidone or atenolol was added, respectively. Arterial
      variables, including radial artery mass and common carotid artery compliance,
      were calculated from noninvasive measurements of internal diameter and wall
      thickness with the use of high resolution echo-tracking systems at baseline and
      after 5 and 9 months. RESULTS: During treatment, blood pressure and arterial
      variables changed to the same extent in both groups. After a 9-month treatment,
      systolic, diastolic and pulse pressures and radial artery wall thickness, mass
      and thickness/radius ratio decreased significantly (p < 0.01), whereas carotid
      compliance increased (p < 0.001). The decrease in radial artery thickness/radius
      ratio after a 9-month treatment was significantly related to the reduction in
      pulse pressure (p < 0.01), whereas the improvement in carotid compliance was
      related to the reduction in mean arterial pressure (p < 0.01). In healthy
      subjects and untreated hypertensive patients, radial artery diameter, wall
      thickness and thickness/radius ratio and carotid artery compliance did not change
      significantly during a 9-month observation period. CONCLUSIONS: These results
      indicate that in elderly hypertensive patients, both angiotensin-converting
      enzyme inhibitor- and diuretic combination-based treatments can reduce radial
      artery wall hypertrophy and improve carotid artery compliance.

PMID- 9562009
TI  - Coronary endothelial dysfunction after Kawasaki disease: evaluation by
      intracoronary injection of acetylcholine.
AB  - OBJECTIVES: This study sought to assess the endothelial function of long-term
      coronary artery lesions in patients with Kawasaki disease (KD). BACKGROUND: The
      vascular function of the coronary arteries in children with long-term KD remains
      uncertain. We report our findings of the vascular response of the coronary
      arteries to intracoronary injection of acetylcholine (ACh) in patients with KD.
      METHODS: A total of 35 patients (25 patients with KD and 10 control subjects)
      were examined using coronary angiography. Individual arteries were divided into
      four groups according to the type of the coronary artery lesion: group 1
      consisted of 25 sites with regressed aneurysms. These aneurysms had developed in
      the acute stage but had subsequently regressed and demonstrated normal findings
      on the follow-up coronary angiogram. Group 2 consisted of 24 sites with
      persistent aneurysms. Group 3 involved 60 angiographically normal sites in the
      same patients as those in group 1 or 2. Group 4 consisted of 30 sites in control
      subjects who had congenital heart disease with normal coronary arteries. During
      coronary angiography we infused 15 microg of ACh chloride into the coronary
      artery. The lumen diameters were measured using a cine videodensitometric
      analyzer to study the distensibility of the coronary artery wall. RESULTS: The
      mean (+/-SD) change in diameter was an increase of 11.71+/-12.34% in group 3
      (coronary arteries without lesions in patients with KD) and 12.21+/-9.71% in the
      control group, demonstrating marked vasodilation in both groups. In contrast, the
      changes in the regressed aneurysms of group 1 and in the persistent aneurysms of
      group 2 were -2.65+/-12.12% and -0.08+/-6.51%, respectively, demonstrating no
      change or mild vasoconstriction. The change in groups 1 and 2 was significantly
      less than that in group 3 or in the control group. Group 3 showed no significant
      difference from the control group. CONCLUSIONS: These findings suggest that long
      term coronary artery lesions, even after aneurysm regression, may have impaired
      endothelial function. A long-term follow-up study for those patients is
      essential.

PMID- 9562010
TI  - Hypertrophic cardiomyopathy: role of the implantable cardioverter-defibrillator.
AB  - OBJECTIVES: We report the occurrence of cardiac events during long-term follow-up
      in patients with hypertrophic cardiomyopathy (HCM) after cardioverter
      defibrillator implantation. BACKGROUND: The identification of patients at high
      risk for sudden death and the prevention of recurrence of sudden death in HCM
      represents a difficult problem. METHODS: We retrospectively analyzed the
      occurrence of cardiac events during follow-up of 13 patients with HCM who
      received an implantable cardioverter-defibrillator (ICD) because of aborted
      sudden death (n = 10) or sustained ventricular tachycardia (n = 3) (group I).
      Findings were compared with those in 215 patients with an ICD and other
      structural heart disease or idiopathic ventricular fibrillation (group II).
      RESULTS: After a mean (+/-SD) follow-up period of 26+/-18 months, 2 of 13
      patients in group I received appropriate shocks. The calculated cumulative
      incidence of shocks was 21% in group I and 66% in group II after 40 months (p <
      0.05). We observed a low incidence of recurrence of ventricular
      tachycardia/fibrillation during follow-up in patients with HCM. No deaths
      occurred. CONCLUSIONS: Our data suggest that ventricular tachyarrhythmias may not
      always be the primary mechanism of syncope and sudden death in patients with HCM.
      The ICD seems to have a less important impact on prognosis in patients with HCM
      than in patients with other etiologies of aborted sudden death.

PMID- 9562011
TI  - Is the implantable defibrillator indicated in patients with hypertrophic
      cardiomyopathy and aborted sudden death?

PMID- 9562012
TI  - Alterations of the architecture of subendocardial arterioles in patients with
      hypertrophic cardiomyopathy and impaired coronary vasodilator reserve: a possible
      cause for myocardial ischemia.
AB  - OBJECTIVES: The study was designed to investigate the architecture of
      subendocardial arterioles of patients with hypertrophic cardiomyopathy (HCM) and
      angina pectoris with respect to coronary vasodilator reserve. BACKGROUND: There
      is growing evidence that the coronary microvasculature is abnormal in HCM.
      Arterioles, which mainly regulate intramyocardial blood flow, are especially
      suspect. METHODS: Thirteen patients with HCM (50.1+/-12.6 years old, mean value
      +/- SD) were studied after exclusion of any relevant coronary stenoses.
      Subendocardial arterioles (density [n/mm2], wall area [microm2], percent lumen
      area [%lumen], periarteriolar collagen area [microm2]), myocyte diameter (microm)
      and interstitial collagen fraction (Vv%) were evaluated by means of stereologic
      morphometry of transvenous biopsy samples. Coronary blood flow was measured
      quantitatively with the inert chromatographic argon method at basal conditions
      and after dipyridamole (0.5 mg/kg body weight over 4 min intravenously), and
      coronary vasodilator reserve was calculated as the ratio of coronary resistance
      at basal conditions and after pharmacologic vasodilation. Data from five
      normotensive subjects (45.4+/-11 years old, p = NS) served as control data.
      RESULTS: Arteriolar density was diminished by 38% (p = 0.004) and %lumen by 13%
      (p = 0.009) in patients with HCM compared with control subjects. Coronary reserve
      was impaired in patients with HCM (2.28+/-0.6 vs. 5.34+/-1.49, p = 0.003) because
      of higher coronary resistance after vasodilation (0.48+/-0.14 vs. 0.22+/-0.06 mm
      Hg x min x 100 g/ml, p = 0.004). Coronary vasodilator reserve correlated with
      arteriolar density (r = +0.47, p = 0.045) and with %lumen (r = 0.65, p = 0.003).
      CONCLUSIONS: In HCM, the architecture of preterminal subendocardial arterioles is
      altered by a reduced total cross-sectional lumen area, corresponding to an
      impaired coronary vasodilator capacity that may predispose to myocardial
      ischemia.

PMID- 9562013
TI  - Comparative efficacy of the maze procedure for restoration of atrial contraction
      in patients with and without giant left atrium associated with mitral valve
      disease.
AB  - OBJECTIVES: We sought to determine the effectiveness of the maze procedure for
      restoring atrial contraction in patients with and without giant left atrium
      (GLA). BACKGROUND: Although the maze procedure has been reported to be effective
      for refractory atrial fibrillation, it is unknown whether this procedure can
      restore effective atrial contraction in patients with GLA. METHODS: Nineteen
      patients with and 32 patients without GLA were studied with Doppler
      echocardiography before and after the maze procedure. Peak velocity and the time
      velocity integral of the left ventricular diastolic filling wave during atrial
      contraction (A wave) and the atrial filling fraction calculated as the ratio of
      the time-velocity integral of the A wave to that of total diastolic filling were
      compared between patients with and without GLA. A peak A wave velocity > or =10
      cm/s was considered to indicate echocardiographic evidence of effective atrial
      contraction. RESULTS: Regular rhythm with P waves was restored in 10 patients
      (53%) with and 26 (81%, p < 0.05) without GLA. Four patients (21%) with and 21
      patients (66%, p < 0.01) without GLA showed effective atrial contraction by
      echocardiography. Once atrial contraction was resumed, the degree of atrial
      contraction was comparable between patients with and without GLA (17+/-5% vs.
      17+/-4% for atrial filling fraction at 12 months, respectively). CONCLUSIONS:
      Although most patients without GLA had restored atrial contraction by the maze
      procedure, it was resumed in fewer patients with GLA. However, once atrial
      contraction was resumed, the degree of atrial contraction was comparable between
      patients with and without GLA. Therefore, the maze procedure may be an option in
      selected patients with GLA.

PMID- 9562014
TI  - Influence of body height on pulsatile arterial hemodynamic data.
AB  - OBJECTIVES: This study sought to present evidence that short stature is a
      hemodynamic liability, which could explain in part the inverse relation between
      body height and cardiovascular risk. BACKGROUND: Other explanations for the
      association of short stature with increased cardiovascular risk include advancing
      age, reduced pulmonary function, genetic factors, poor childhood nutrition and
      small-caliber coronary arteries. This study adds another factor-the physiologic
      effects of reduced body height on the arterial tree, which increase left
      ventricular work and jeopardize myocardial perfusion. METHODS: Four hundred two
      subjects were studied: 149 with end-stage renal disease and 253 with normal renal
      function. Measurements included blood pressure, body height, cardiac cycle
      length, carotid to femoral artery pulse wave velocity, carotid artery pulse waves
      (by applanation tonometry) and the arrival time of reflected waves. Calculations
      included the carotid augmentation index, carotid artery compliance and the
      diastolic to systolic pressure-time ratio (an index of myocardial supply and
      demand). RESULTS: On linear and stepwise multiple regression, body height
      correlated with all variables except mean blood pressure. CONCLUSIONS: The early
      systolic arrival of reflected waves in short people in this group acts to stiffen
      the aorta and increase the pulsatile effort of the left ventricle, even at the
      same mean blood pressures. Short stature also induces a faster heart rate, which
      increases cardiac minute work and shorten diastole. Stiffening lowers the aortic
      diastolic pressure and, coupled with a shortened diastole, could adversely
      influence myocardial supply. Although indirect, this evidence supports a
      physiologic hypothesis for the body height-cardiovascular risk association.

PMID- 9562015
TI  - Closure of atrial septal defects with the Amplatzer occlusion device: preliminary
      results.
AB  - OBJECTIVES: This study reports our clinical experience with transcatheter closure
      of secundum atrial septal defects (ASDs) in children, using the Amplatzer, a new
      occlusion device. BACKGROUND: None of the devices previously used for
      transcatheter closure of interatrial communications has gained wide acceptance.
      METHODS: We examined the efficacy and safety of the Amplatzer, a new self
      centering septal occluder that consists of two round disks made of Nitinol wire
      mesh and linked together by a short connecting waist. Sixteen patients with
      secundum ASD met established two- and three-dimensional echocardiographic and
      cardiac catheterization criteria for transcatheter closure. The Amplatzer's size
      was chosen to be equal to or 1 mm less than the stretched diameter. The device
      was advanced transvenously into a 7F long guiding sheath and deployed under
      fluoroscopic and ultrasound guidance. Once its position was optimal, it was
      released. RESULTS: The mean ASD diameter by transesophageal echocardiography was
      14.1+/-2.3 mm and was significantly smaller (p < 0.001) than the stretched
      diameter of the ASD (16.8+/-2.4 mm). The mean device diameter was 16.6+/-2.3 mm.
      No complications were observed. After deployment of the prosthesis, there was no
      residual shunt in 13 (81.3%) of 16 patients. In three patients there was trivial
      residual shunt immediately after the procedure that had disappeared in two of
      them at the 3-month follow-up. CONCLUSIONS: The Amplatzer is an efficient
      prosthesis that can be safely applied in children with secundum ASD. However, a
      study including a large number of patients and a longer follow-up period are
      required before this technique can be widely used.

PMID- 9562016
TI  - Transcatheter closure of atrial septal defect: are we there yet?

PMID- 9562017
TI  - Management and outcomes of right atrial isomerism: a 26-year experience.
AB  - OBJECTIVES: We sought to determine, in a large series of patients with right
      atrial isomerism, factors associated with mortality. BACKGROUND: Right atrial
      isomerism is associated with complex congenital heart disease and high morbidity
      and mortality. METHOD: All data from patients diagnosed with right atrial
      isomerism between January 1970 and March 1996 were reviewed. RESULTS: A total of
      91 consecutive patients (54 male) were identified. Most patients (89%) presented
      within the first month of life, 62% at birth. Cardiac abnormalities included
      common atrioventricular (AV) valve (81%), ventricular hypoplasia or single
      ventricle (73%), abnormal ventriculoarterial connections (96%), pulmonary outflow
      tract obstruction (84%), anomalous pulmonary venous drainage (87%) and pulmonary
      vein obstruction (30%). The overall mortality rate was 69%. No interventions were
      planned or performed in 24%, 95% of whom died. The mortality rate for patients
      requiring their first cardiovascular operation in the neonatal period was 75%
      versus 51% for those with later first operations (p < 0.05). The surgical
      mortality rate for patients undergoing pulmonary vein repair was 95%. Overall
      survival estimates were 71% at 1 month, 49% at 1 year and 35% at 5 years.
      Independent risk factors for decreased time to death included the absence of
      pulmonary outflow obstruction (relative risk [RR] 2.23, p < 0.03), presence of
      major AV valve anomaly (RR 5.23, p < 0.03) and obstructed pulmonary veins (RR
      5.43, p < 0.0001). CONCLUSIONS: Right atrial isomerism continues to have an
      associated high mortality despite surgical innovations. Management of pulmonary
      vein obstruction remains a serious problem and is associated with high mortality.

PMID- 9562018
TI  - Development of a double-chambered right ventricle after repair of tetralogy of
      Fallot.
AB  - OBJECTIVES: We sought to determine the frequency, etiology and progressive nature
      of midcavity obstruction in patients after primary repair of tetralogy of Fallot
      (TOF). BACKGROUND: Midcavity obstruction (double-chambered right ventricle
      [DCRV]) represents a significant portion of reoperations in patients who have had
      TOF repair. This group is still poorly defined. METHODS: A retrospective review
      of clinical, echocardiographic and catheterization data for all patients with TOF
      who later underwent reoperation for DCRV was performed. RESULTS: Between 1973 and
      1995, 552 children <2 years of age underwent primary TOF repair (median age 6.7
      months). Long-term follow-up (median 50 months) was available in 308 children. Of
      these, 17 children subsequently developed DCRV requiring reoperation. The median
      age at initial operation was 7.9 months. During a median follow-up interval of
      43.2 months, murmur intensity increased in all patients, and the average
      subpulmonary gradient at catheterization increased from 24+/-10 to 80+/-27 mm Hg
      in seven children (p = 0.002) and at Doppler echocardiography from 14+/-16 to
      89+/-18 mm Hg in five children (p = 0.002). Before reoperation, 6 of the 17
      children were symptomatic. During the operation (median age 55.4 months),
      obstruction was relieved by incision of hypertrophied anomalous muscle bundles in
      all 17 patients, with prominent fibrosis noted in 8 patients. Excessive septal
      and parietal hypertrophy was noted in one child. No new transannular patches were
      required. Recurrent obstruction has reappeared in 3 of these 17 children during
      follow-up. CONCLUSIONS: DCRV is a medium-term complication of TOF repair in
      infants, with a minimal incidence of 3.1% (95% CI 1.8% to 4.9%). The condition is
      progressive and is due to anomalous muscle bundle hypertrophy or fibrosis, or
      both, which may represent displaced insertion of a moderator band. Further
      reobstruction does occur; continued careful follow-up is therefore essential.

PMID- 9562019
TI  - Lack of adenosine causes myocardial refractoriness.
AB  - OBJECTIVES: This study sought to investigate the myocardial mechanisms causing
      refractoriness to ischemic preconditioning in pigs. BACKGROUND: Ischemic
      preconditioning in the pig vanishes after 60 min and cannot be reinstated by a
      second cycle of brief coronary occlusions at this time point. Ischemic
      preconditioning has been shown to be mediated by adenosine A1-receptors. Because
      myocardial adenosine production during ischemia ceases as the number of repeated
      brief ischemic episodes increases, we hypothesized that this lack of adenosine
      may cause this myocardial refractoriness. METHODS: In open chest pigs, ischemic
      preconditioning was achieved by repeated brief coronary occlusions. Myocardial
      adenosine content was assessed by high performance liquid chromatographic
      analysis of serial myocardial biopsy samples; infarct size (percent infarcted
      area of the area at risk) was determined using tetrazolium salts. RESULTS:
      Ischemic preconditioning by two cycles of occlusion of the left anterior
      descending coronary artery (10 min) and reperfusion (30 min) decreased infarct
      size ([mean +/- SEM] 40.4+/-2.9%; control: 76.9+/-1.8%, p < 0.001). Prolonging
      the second reperfusion period to 60 min caused ischemic preconditioning to vanish
      (79.0+/-0.5%) and caused refractoriness to a second cycle of preconditioning
      (70.0+/-2.0%). Myocardial adenosine content increased only during the first
      coronary occlusion (baseline: 110.9+/-42.0 nmol/g dry weight; first coronary
      occlusion: 1,686.2+/-244.1, p < 0.001) but not during subsequent coronary
      occlusions. In refractory myocardium, intramyocardial microinfusion of the
      adenosine A1-receptor agonist N6-cyclohexyladenosine (CHA [0.3 mmol/liter]) again
      decreased infarct size (27.4+/-7.0%, p < 0.001 vs. control). CONCLUSIONS:
      Myocardial refractoriness may be caused by the inability to produce adenosine
      endogenously. In refractory myocardium, application of CHA reinduces
      cardioprotection.

PMID- 9562021
TI  - Ischemic preconditioning: the issues of refractoriness and tolerance.

PMID- 9562020
TI  - Prolonging the delayed phase of myocardial protection: repetitive adenosine A1
      receptor activation maintains rabbit myocardium in a preconditioned state.
AB  - OBJECTIVES: This study was designed to examine whether the myocardium can be
      maintained in a protected state by extending the delayed phase of
      cardioprotection with chronic, intermittent adenosine A1 receptor activation.
      BACKGROUND: Several recent studies have explored the temporal characteristics of
      the protective effects of ischemic preconditioning. Two distinct phases of
      myocardial protection have been described: the short-lived immediate phase, or
      "classic" preconditioning, and the delayed phase, or "second window of
      protection" (SWOP). Previous studies have examined the potential for extending
      the duration of classic preconditioning by repeated application of the
      preconditioning stimulus. Pretreatment with either multiple episodes of ischemia
      or continuous infusion of a selective adenosine A1 receptor agonist, 2-chloro-N6
      cyclopentyladenosine (CCPA), resulted in attenuation of the protective effects of
      preconditioning, implying downregulation of the receptors involved in triggering
      classic preconditioning. METHODS: Male New Zealand White rabbits were treated
      with repeated intravenous boluses of CCPA, 100 microg/kg body weight, or 0.9%
      saline at 48-h intervals. Forty-eight hours after the fifth dose (day 10), the
      animals were anesthetized and subjected to 30 min of coronary occlusion, followed
      by 120 min of reperfusion. Infarct size was determined as a percentage of
      myocardial risk volume using tetrazolium staining. To further explore whether the
      rabbits had developed tolerance to the effects of adenosine A1 receptor
      activation, a subgroup of animals were treated with a further bolus of CCPA, 100
      microg/kg, at the end of the reperfusion period, and the hemodynamic response was
      monitored for 10 min before excision of the heart. RESULTS: Pretreatment with
      intermittent doses of CCPA resulted in a 42% reduction in the infarct to risk
      ratio compared with vehicle pretreatment (26.6+/-3.7% vs. 45.9+/-5.5%, p < 0.01).
      Furthermore, CCPA treatment at the end of reperfusion resulted in identical
      hypotension and bradycardia in both groups. CONCLUSIONS: We conclude that rabbits
      can be maintained in a protected state against myocardial infarction by repeated
      activation of adenosine A1 receptors, with no evidence of tachyphylaxis to the
      infarct-limiting or hemodynamic effects of CCPA. This finding suggests that
      adenosine A1 receptor activation may hold promise as a new approach to long-term
      cardioprotection.

PMID- 9562022
TI  - Photoremodeling of arterial wall reduces restenosis after balloon angioplasty in
      an atherosclerotic rabbit model.
AB  - OBJECTIVES: This study evaluated the long-term impact of endoluminal low power
      red laser light (LPRLL) on restenosis in an atherosclerotic rabbit model.
      BACKGROUND: Despite widespread application of balloon angioplasty for treatment
      of coronary artery disease, restenosis limits its clinical benefits. Restenosis
      is a complex process and may be partly attributed to the inability of the
      vascular endothelium to regenerate and cover the denuded area at the site of
      arterial injury. We previously demonstrated that LPRLL stimulates endothelial
      cell proliferation in vitro and contributes to rapid endothelial regeneration
      after balloon injury in nonatherosclerotic rabbits. METHODS: Rabbit abdominal
      aortas (n = 12) were treated in separate zones with balloon dilation and balloon
      dilation plus laser illumination. Endoluminal laser therapy was performed using a
      laser-balloon catheter delivering a single dose of 10 mW for 3 min from a helium
      neon laser (632 nm). Angiography was performed before and after treatment and was
      repeated 8 weeks before harvesting the aortas. RESULTS: Quantitative angiographic
      analysis demonstrated no differences in the minimal lumen diameter (MLD) between
      the two zones before treatment; an increase in the MLD in both zones after
      balloon angioplasty and a significant versus slight reduction of the MLD in the
      balloon treatment versus balloon plus laser zones at 8 weeks. Histologic
      examination showed a very high level of myointimal hyperplasia in the balloon
      treatment zones but a minimal level in the LPRLL-treated zones. Morphometric
      analysis revealed a statistically significant difference in the lumen area,
      intimal area and intima/media ratio between the balloon versus balloon plus laser
      treatment sites. CONCLUSIONS: Our experimental data indicate that endoluminal
      irradiation with LPRLL prevents restenosis after balloon angioplasty in an
      atherosclerotic rabbit model.

PMID- 9562024
TI  - Myocardial tactile stiffness: a variable of regional myocardial function.
AB  - OBJECTIVES: We developed a new sensor system for in situ measurement of
      myocardial tactile stiffness-stiffness in a direction perpendicular to the wall
      and validated its use for providing a reasonable estimation of regional
      myocardial function. BACKGROUND: Numerous attempts have been made to directly
      assess regional myocardial function. The complexity and highly invasive nature of
      the measuring devices have hampered their in situ application. METHODS: In open
      chest mongrel dogs, myocardial tactile stiffness, ventricular pressure and
      ventricular volume were monitored. Under the preload reduction, these variables
      were measured to determine the relation between the end-systolic pressure-volume
      relation (ESPVR) and the end-systolic tactile stiffness-volume relation (ESSVR).
      The changes in myocardial tactile stiffness were monitored in the regional
      ischemic myocardial model and infarcted model to evaluate their usefulness as
      indexes of regional myocardial function. RESULTS: Myocardial tactile stiffness
      changed cyclically and followed a time course similar to left ventricular
      pressure. When preload was altered, the ESSVR was as linear as the ESPVR. The
      slope of the ESSVR and that of the ESPVR showed a strong correlation over a wide
      range of contractility. These results suggest that myocardial tactile stiffness
      can be a good index of regional wall stress or fiber stress. End-systolic
      myocardial tactile stiffness of ischemic and infarcted regions decreased
      significantly, with a concomitant increase in end-diastolic stiffness compared
      with that of intact myocardium. CONCLUSIONS: Using our tactile sensor system,
      regional myocardial tactile stiffness of a beating heart was measured with
      reasonable temporal resolution. We consider myocardial tactile stiffness to be a
      useful index of regional myocardial function.

PMID- 9562023
TI  - Conjugated equine estrogens inhibit progression of atherosclerosis but have no
      effect on intimal hyperplasia or arterial remodeling induced by balloon catheter
      injury in monkeys.
AB  - OBJECTIVES: This study sought to determine the effects of estrogen treatment on
      atherosclerosis progression and the proliferative and structural responses of the
      atherosclerotic arteries to injury. BACKGROUND: Estrogen treatment suppresses the
      intimal response to arterial injury in nonatherosclerotic rodents and rabbits and
      inhibits the in vitro proliferation of smooth muscle cells. However, the effect
      of estrogen on the response of atherosclerotic arteries to transmural injury, as
      occurs in balloon catheter angioplasty in humans, is unknown. METHODS: Forty-six
      ovariectomized cynomolgus monkeys were fed an atherogenic diet for 30 months; 25
      received 175 microg/day of conjugated equine estrogens, and 21 served as
      untreated control animals. All animals underwent balloon catheter injury of the
      left iliac artery. Subsets of animals underwent a necropsy study at 4, 7, 14 and
      28 days after injury; injured and contralateral (uninjured) arteries were
      pressure-fixed and evaluated morphometrically. RESULTS: Estrogen treatment
      resulted in a 37% decrease (p < 0.05) in atherosclerosis (plaque area) in the
      uninjured artery. In response to injury, arterial cell proliferation increased at
      days 4 and 7, and intimal area was increased two- to threefold at day 28 (p <
      0.05). Although estrogen treatment resulted in a trend toward decreased arterial
      cell proliferation at day 4, there was evidence of increased cell proliferation
      in both media and intima at day 7 (p < 0.05). However, there was no effect of
      estrogen treatment on intimal area or indexes of arterial remodeling in the
      injured artery at day 28 (p > 0.4). CONCLUSIONS. In contrast to previous studies
      of nonatherosclerotic animals, the results indicate that in the circumstance of
      transmural injury to arteries of primates with preexisting atherosclerosis,
      estrogen does not suppress arterial neointimal or structural responses to injury.

PMID- 9562025
TI  - What is the most important thing in your life?

PMID- 9562026
TI  - ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia
      devices: a report of the American College of Cardiology/American Heart
      Association Task Force on Practice Guidelines (Committee on Pacemaker
      Implantation).

PMID- 9562027
TI  - Antioxidants in Chinese green tea.

PMID- 9562028
TI  - Predicting mortality after coronary artery bypass graft surgery.

PMID- 9562029
TI  - Myocardial viability.

PMID- 9562030
TI  - Increased neopterin in patients with chronic and acute coronary syndromes.

PMID- 9562031
TI  - Ion channels and early development of neural cells.
AB  - In this review we underscore the merits of using voltage-dependent ion channels
      as markers for neuronal differentiation from the early stages of uncommitted
      embryonic blastomeres. Furthermore, a fairly large part of the review is devoted
      to the descriptions of the establishment of a simple model system for neural
      induction derived from the cleavage-arrested eight-cell ascidian embryo by
      pairing a single ectodermal with a single vegetal blastomere as a competent and
      an inducer cell, respectively. The descriptions are focused particularly on the
      early developmental processes of various ion channels in neuronal and other
      excitable membranes observed in this extraordinarily simple system, and we
      compare these results with those in other significant and definable systems for
      neural differentiation. It is stressed that this simple system, for which most of
      the electronic and optical methods and various injection experiments are
      applicable, may be useful for future molecular physiological studies on the
      intracellular process of differentiation of the early embryonic cells. We have
      also highlighted the importance of suppressive mechanisms for cellular
      differentiation from the experimental results, such as epidermal commitment of
      the cleavage-arrested one-cell Halocynthia embryos or suppression of epidermal
      specific transcription of inward rectifier channels by neural induction signals.
      It was suggested that reciprocal suppressive mechanisms at the transcriptional
      level may be one of the key processes for cellular differentiation, by which
      exclusivity of cell types is maintained.

PMID- 9562032
TI  - Cold-induced thermoregulation and biological aging.
AB  - Aging is associated with diminished cold-induced thermoregulation (CIT). The
      mechanisms accounting for this phenomenon have yet to be clearly elucidated but
      most likely reflect a combination of increased heat loss and decreased metabolic
      heat production. The inability of the aged subject to reduce heat loss during
      cold exposure is associated with diminished reactive tone of the cutaneous
      vasculature and, to a lesser degree, alterations in the insulative properties of
      body fat. Cold-induced metabolic heat production via skeletal muscle shivering
      thermogenesis and brown adipose tissue nonshivering thermogenesis appears to
      decline with age. Few investigations have directly linked diminished skeletal
      muscle shivering thermogenesis with the age-related reduction in cold-induced
      thermoregulatory capacity. Rather, age-related declines in skeletal muscle mass
      and metabolic activity are cited as evidence for decreased heat production via
      shivering. Reduced mass, GDP binding to brown fat mitochondria, and uncoupling
      protein (UCP) levels are cited as evidence for attenuated brown adipose tissue
      cold-induced nonshivering thermogenic capacity during aging. The age-related
      reduction in brown fat nonshivering thermogenic capacity most likely reflects
      altered cellular signal transduction rather than changes in neural and hormonal
      signaling. The discussion in this review focuses on how alterations in CIT during
      the life span may offer insight into possible mechanisms of biological aging.
      Although the preponderance of evidence presented here demonstrates that CIT
      declines with chronological time, the mechanism reflecting this attenuated
      function remains to be elucidated. The inability to draw definitive conclusions
      regarding biological aging and CIT reflects the lack of a clear definition of
      aging. It is unlikely that the mechanisms accounting for the decline in cold
      induced thermoregulation during aging will be determined until biological aging
      is more precisely defined.

PMID- 9562033
TI  - The filament lattice of striated muscle.
AB  - The filament lattice of striated muscle is an overlapping hexagonal array of
      thick and thin filaments within which muscle contraction takes place. Its
      structure can be studied by electron microscopy or X-ray diffraction. With the
      latter technique, structural changes can be monitored during contraction and
      other physiological conditions. The lattice of intact muscle fibers can change
      size through osmotic swelling or shrinking or by changing the sarcomere length of
      the muscle. Similarly, muscle fibers that have been chemically or mechanically
      skinned can be compressed with bathing solutions containing very large inert
      polymeric molecules. The effects of lattice change on muscle contraction in
      vertebrate skeletal and cardiac muscle and in invertebrate striated muscle are
      reviewed. The force developed, the speed of shortening, and stiffness are
      compared with structural changes occurring within the lattice. Radial forces
      between the filaments in the lattice, which can include electrostatic, Van der
      Waals, entropic, structural, and cross bridge, are assessed for their
      contributions to lattice stability and to the contraction process.

PMID- 9562034
TI  - Contributions of microbes in vertebrate gastrointestinal tract to production and
      conservation of nutrients.
AB  - The vertebrate gastrointestinal tract is populated by bacteria and, in some
      species, protozoa and fungi that can convert dietary and endogenous substrates
      into absorbable nutrients. Because of a neutral pH and longer digesta retention
      time, the largest bacterial populations are found in the hindgut or large
      intestine of mammals, birds, reptiles, and adult amphibians and in the foregut of
      a few mammals and at least one species of bird. Bacteria ferment carbohydrates
      into short-chain fatty acids (SCFA), convert dietary and endogenous nitrogenous
      compounds into ammonia and microbial protein, and synthesize B vitamins.
      Absorption of SCFA provides energy for the gut epithelial cells and plays an
      important role in the absorption of Na and water. Ammonia absorption aids in the
      conservation of nitrogen and water. A larger gut capacity and longer digesta
      retention time provide herbivores with additional SCFA for maintenance energy and
      foregut-fermenting and copoprophagic hindgut-fermenting species with access to
      microbially synthesized protein and B vitamins. Protozoa and fungi also
      contribute nutrients to the host. This review discusses the contributions of gut
      microorganisms common to all vertebrates, the numerous digestive strategies that
      allow herbivores to maximize these contributions, and the effects of low-fiber
      diets and discontinuous feeding schedules on these microbial digestive processes.

PMID- 9562035
TI  - Transduction mechanisms in vertebrate olfactory receptor cells.
AB  - Considerable progress has been made in the understanding of transduction
      mechanisms in olfactory receptor neurons (ORNs) over the last decade. Odorants
      pass through a mucus interface before binding to odorant receptors (ORs). The
      molecular structure of many ORs is now known. They belong to the large class of G
      protein-coupled receptors with seven transmembrane domains. Binding of an odorant
      to an OR triggers the activation of second messenger cascades. One second
      messenger pathway in particular has been extensively studied; the receptor
      activates, via the G protein Golf, an adenylyl cyclase, resulting in an increase
      in adenosine 3',5'-cyclic monophosphate (cAMP), which elicits opening of cation
      channels directly gated by cAMP. Under physiological conditions, Ca2+ has the
      highest permeability through this channel, and the increase in intracellular Ca2+
      concentration activates a Cl- current which, owing to an elevated reversal
      potential for Cl-, depolarizes the olfactory neuron. The receptor potential
      finally leads to the generation of action potentials conveying the chemosensory
      information to the olfactory bulb. Although much less studied, other transduction
      pathways appear to exist, some of which seem to involve the odorant-induced
      formation of inositol polyphosphates as well as Ca2+ and/or inositol
      polyphosphate -activated cation channels. In addition, there is evidence for
      odorant-modulated K+ and Cl- conductances. Finally, in some species, ORNs can be
      inhibited by certain odorants. This paper presents a comprehensive review of the
      biophysical and electrophysiological evidence regarding the transduction
      processes as well as subsequent signal processing and spike generation in ORNs.

PMID- 9562036
TI  - Adult cortical dynamics.
AB  - There are many influences on our perception of local features. What we see is not
      strictly a reflection of the physical characteristics of a scene but instead is
      highly dependent on the processes by which our brain attempts to interpret the
      scene. As a result, our percepts are shaped by the context within which local
      features are presented, by our previous visual experiences, operating over a wide
      range of time scales, and by our expectation of what is before us. The substrate
      for these influences is likely to be found in the lateral interactions operating
      within individual areas of the cerebral cortex and in the feedback from higher to
      lower order cortical areas. Even at early stages in the visual pathway, cells are
      far more flexible in their functional properties than previously thought. It had
      long been assumed that cells in primary visual cortex had fixed properties,
      passing along the product of a stereotyped operation to the next stage in the
      visual pathway. Any plasticity dependent on visual experience was thought to be
      restricted to a period early in the life of the animal, the critical period.
      Furthermore, the assembly of contours and surfaces into unified percepts was
      assumed to take place at high levels in the visual pathway, whereas the receptive
      fields of cells in primary visual cortex represented very small windows on the
      visual scene. These concepts of spatial integration and plasticity have been
      radically modified in the past few years. The emerging view is that even at the
      earliest stages in the cortical processing of visual information, cells are
      highly mutable in their functional properties and are capable of integrating
      information over a much larger part of visual space than originally believed.

PMID- 9562037
TI  - Transporters for cationic amino acids in animal cells: discovery, structure, and
      function.
AB  - The structure and function of the four cationic amino acid transporters
      identified in animal cells are discussed. The systems differ in specificity,
      cation dependence, and physiological role. One of them, system y+, is selective
      for cationic amino acids, whereas the others (B[0,+], b[0,+], and y+ L) also
      accept neutral amino acids. In recent years, cDNA clones related to these
      activities have been isolated. Thus two families of proteins have been
      identified: 1) CAT or cationic amino acid transporters and 2) BAT or broad-scope
      transport proteins. In the CAT family, three genes encode for four different
      isoforms [CAT-1, CAT-2A, CAT-2(B) and CAT-3]; these are approximately 70-kDa
      proteins with multiple transmembrane segments (12-14), and despite their
      structural similarity, they differ in tissue distribution, kinetics, and
      regulatory properties. System y+ is the expression of the activity of CAT
      transporters. The BAT family includes two isoforms (rBAT and 4F2hc); these are 59
      to 78-kDa proteins with one to four membrane-spanning segments, and it has been
      proposed that these proteins act as transport regulators. The expression of rBAT
      and 4F2hc induces system b[0,+] and system y+ L activity in Xenopus laevis
      oocytes, respectively. The roles of these transporters in nutrition,
      endocrinology, nitric oxide biology, and immunology, as well as in the genetic
      diseases cystinuria and lysinuric protein intolerance, are reviewed. Experimental
      strategies, which can be used in the kinetic characterization of coexpressed
      transporters, are also discussed.

PMID- 9562038
TI  - The free radical theory of aging matures.
AB  - The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly
      attracting the interest of the mainstream of biological research. From its
      origins in radiation biology, through a decade or so of dormancy and two decades
      of steady phenomenological research, it has attracted an increasing number of
      scientists from an expanding circle of fields. During the past decade, several
      lines of evidence have convinced a number of scientists that oxidants play an
      important role in aging. (For the sake of simplicity, we use the term oxidant to
      refer to all "reactive oxygen species," including O2-., H2O2, and .OH, even
      though the former often acts as a reductant and produces oxidants indirectly.)
      The pace and scope of research in the last few years have been particularly
      impressive and diverse. The only disadvantage of the current intellectual ferment
      is the difficulty in digesting the literature. Therefore, we have systematically
      reviewed the status of the free radical theory, by categorizing the literature in
      terms of the various types of experiments that have been performed. These include
      phenomenological measurements of age-associated oxidative stress, interspecies
      comparisons, dietary restriction, the manipulation of metabolic activity and
      oxygen tension, treatment with dietary and pharmacological antioxidants, in vitro
      senescence, classical and population genetics, molecular genetics, transgenic
      organisms, the study of human diseases of aging, epidemiological studies, and the
      ongoing elucidation of the role of active oxygen in biology.

PMID- 9562039
TI  - Antigenic homology of HIV-1 GP41 and human platelet glycoprotein GPIIIa (integrin
      beta3).
AB  - Fifty-eight of 89 serum samples (65.17%) from HIV-1-infected individuals at
      various disease stages contain antibodies that react with a platelet peptide
      located in the cytoplasmic domain of integrin beta3, glycoprotein GPIIIa (aa749
      761; sequence DRKEFAKFEEERA). Rabbit polyclonal antibodies raised against the
      synthetic platelet peptide also react with the structurally homologous HIV-1 gp41
      derived peptide (EKNEQELLELDKW(A)) and bind to a Western blot band with molecular
      weight corresponding to HIV-1 gp41. These findings point to molecular mimicry
      between HIV-1 and a human membrane protein found in platelets and other cells
      that could be of pathologic consequence.

PMID- 9562040
TI  - HTLV-I and HTLV-II virus expression increase with HIV-1 coinfection.
AB  - Coinfections with HIV-1 and HTLV-I or HTLV-II have been associated with unique
      immunophenotypes and an increased risk for development of neurodegenerative
      conditions. These findings may result from an increased HTLV-I or II viral burden
      in dually infected individuals. To investigate this possibility, HTLV-I/II
      tax/rex messenger RNA and viral antigen expression in peripheral blood
      mononuclear cells (PBMCs) were measured in 37 HTLV-I- or HTLV-II-infected
      subjects with or without HIV-1 coinfection. Tax/rex messenger RNA was detected in
      14 of 24 PBMC samples from dually infected subjects, compared with only 1 of 13
      PBMC samples from singly infected subjects (58% versus 7%; p < .003). The reverse
      transcription-polymerase chain reaction (RT-PCR) assay correlated with HTLV-I/II
      viral antigen detection in PBMC cultures but not with HIV-1 viral load levels in
      plasma. These findings may provide clues regarding the pathophysiologic
      consequences of HIV/HTLV-I and HIV/HTLV-II coinfections.

PMID- 9562041
TI  - Potential SECIS elements in HIV-1 strain HXB2.
AB  - It has been proposed on the basis of sequence analysis that HIV-1 encodes a
      protein containing the amino acid selenocysteine (Sec). Selenocysteine is known
      to be incorporated into protein in response to a specific RNA secondary structure
      motif within the mRNA that is being translated. This RNA motif, the
      selenocysteine insertion sequence (SECIS) element, has not yet been identified in
      the HIV genome by either biologic or computation methods. This report uses
      computer-based sequence analysis to identify those locations in HIV-1 strain HXB2
      where the current model of the SECIS element could exist. One particularly good
      match to the SECIS element occurs in an interesting location, spanning the end of
      env and the start of nef, in a position theoretically capable of directing the
      previously proposed Sec incorporation.

PMID- 9562042
TI  - Does pregnancy influence the course of HIV infection? Evidence from two large
      Swiss cohort studies.
AB  - The question whether the natural history of HIV infection in women is affected by
      pregnancy has not so far been convincingly answered. We used prospective cohort
      data to compare pregnant and nonpregnant HIV-infected women during follow-up
      within the Swiss HIV Cohort Study (SHCS) and the Swiss Collaborative HIV and
      Pregnancy Study (SCHPS). Pregnant women were eligible if a CD4 cell count had
      been made before conception had taken place. Additional inclusion criteria were a
      pregnancy completed to delivery during follow-up and an observation period of at
      least 6 months after delivery. Thirty-two women who fulfilled these criteria were
      compared with 416 controls, matched for age and CD4 cell count at entry, who had
      not been pregnant during follow-up. Mean follow-up time was 4.8 years for
      pregnant women and 3.6 years for controls. The rate of any AIDS-defining event
      was higher in pregnant women (rate ratio [RR] from Cox regression, 1.92; 95%
      confidence interval [CI], 0.80-4.64) but this did not reach statistical
      significance (p = .15). A statistically significant difference (p = .008) emerged
      only for one AIDS-defining event, recurrent bacterial pneumonia (RR, 7.98; 95%
      CI, 1.73-36.8). The rate of death was similar in the two groups (RR, 1.14; 95%
      CI, 0.48-2.72; p = .8). Our results thus indicate that, after taking CD4 cell
      counts before conception into account, acceleration of disease progression is
      inconsistent among HIV-infected women who become pregnant during follow-up.

PMID- 9562043
TI  - Levels of HIV RNA are quantitatively related to prior weight loss in HIV
      associated wasting.
AB  - Thirty-three patients referred to a wasting clinic were evaluated to assess
      whether levels of HIV RNA were related to the magnitude of prior weight loss.
      Their median RNA level was 46,887 gene copies/ml (range, <200-510,070 gene
      copies/ml) at the time of referral. Patients had lost 10.5 +/- 6.4 kg over 461 +/
      304 days. RNA levels were correlated with the absolute amount and percentage of
      weight lost as well as the difference in body mass index (BMI) at the prior
      maximal and minimal recorded weights (r = 0.7, 0.67, 0.69; p = .0001 for the
      comparisons). The magnitude of these changes increased across strata of HIV RNA
      levels (p < or = .004), previously defined as associated with increasing risk for
      disease progression. The other parameter that could be associated with weight
      loss was the CD4 lymphocyte count (r = -0.43; p = .01). Low levels of
      testosterone and measures of body cell mass, fat free mass, or fat mass within 6
      weeks of the RNA level could not be related to weight loss, change in BMI, or RNA
      levels. Thirty-two of the patients had chronic, relentless weight loss; in 15 of
      these subjects, no apparent secondary opportunistic complications were associated
      with weight loss or gastrointestinal symptoms to impair energy intake. Levels of
      HIV replication appear to be causally related to the magnitude of weight loss in
      some patients with wasting.

PMID- 9562044
TI  - Susceptibility of peripheral blood mononuclear cells to apoptosis is correlated
      to plasma HIV load.
AB  - OBJECTIVES: To quantify spontaneous and activation-induced apoptosis in
      peripheral blood mononuclear cells (PBMC) of HIV-infected patients and to look
      for correlations between PBMC apoptosis levels, stages of HIV disease, CD4 count,
      and plasma viral load. STUDY POPULATIONS: 75 consecutive inpatients and
      outpatients infected with HIV (mean CD4 count, 202 +/- 182 x 10(6)/L; mean plasma
      viral load, 4 +/- 1.29 log10 RNA copies/ml) and a control group composed of 18
      healthy, HIV-negative adults. METHODS: Spontaneous apoptosis was detected at the
      single-cell level by direct incorporation of fluorescein-deoxyuridine
      triphosphate (dUTP) in PBMC DNA strand breaks. Activation-induced apoptosis was
      determined after in vitro stimulation with anti-CD3 antibodies and interleukin-2
      (IL-2). RESULTS: Spontaneous apoptosis was low in patients and controls, whereas
      activation-induced apoptosis was significantly higher in HIV-infected patients
      (5.22 +/- 4.32% versus 2.46 +/- 1.77%, respectively; p = .009). The degree of
      activation-induced apoptosis was positively correlated with the plasma viral load
      (r = 0.29; p = .029) and negatively correlated with the CD4 count (r = -0.37; p =
      .0009). Although activation-induced apoptosis was significantly higher in
      patients fulfilling AIDS criteria, it did not differ significantly between
      patients with an acute AIDS-defining event and those with stable disease.
      CONCLUSION: Susceptibility of PBMC to apoptosis in HIV-1-infected patients is
      correlated to the plasma viral load and the stage of the disease.

PMID- 9562045
TI  - Costs and outcomes of AIDS care: comparing a health maintenance organization with
      fee-for-service systems in the Boston Health Study.
AB  - OBJECTIVE: A 4-month observational cohort study was performed to compare the
      performance of one health maintenance organization (HMO) with two fee-for-service
      (FFS) systems in Boston, Massachusetts in treating 255 patients with AIDS. MAIN
      OUTCOME MEASURES: Total 4-month costs; cost subcomponents, including inpatient,
      outpatient, home care, and zidovudine costs; functional status (difficulties with
      activities of daily living); and satisfaction with care. RESULTS: Compared with
      FFS patients, HMO patients were better educated, more often white, less often on
      Medicaid, and more often reported homosexual or bisexual behaviors as HIV risk
      factors (all factors, p = .001). Both groups had similar duration of AIDS,
      baseline hemoglobin levels, and leukocyte counts. Total 4-month costs at the HMO
      were significantly lower than those in the FFS settings ($4799 U.S. versus $8540
      U.S.; p = .013), as were outpatient costs ($1131 U.S. versus $1614 U.S.; p =
      .001), after adjustment for sociodemographic factors, baseline functioning, main
      HIV risk factor, and other clinical variables. Adjusted physical functioning (p =
      .32) and patient satisfaction (p = .82). were similar between systems.
      CONCLUSIONS: The HMO had significantly lower total costs without any observable
      decrement in functional outcomes or patient satisfaction. The largest component
      of these cost savings came from reduced spending on inpatient care, but the HMO
      also spent less on outpatient and home care. Better coordination of care at the
      HMO may have been responsible for these lower costs.

PMID- 9562046
TI  - Toward a better understanding of health-related quality of life: a comparison of
      the Medical Outcomes Study HIV Health Survey (MOS-HIV) and the HIV Overview of
      Problems-Evaluation System (HOPES).
AB  - Although enthusiasm for measuring health-related quality of life (HRQL) in
      clinical trials exists, information is limited on the meaning of scores. We
      examined the relation between scores from the 34-item Medical Outcomes Study HIV
      Health Survey (MOS-HIV) and the more detailed HIV Overview of Problems-Evaluation
      System (HOPES) using the responses of 318 HIV-infected outpatients being treated
      in Los Angeles and Baltimore. With the HOPES problem statements as independent
      variables, statistically significant predictors of the variation in MOS-HIV
      scores for the Physical Function, Mental Health, and Energy/Fatigue scales were
      identified using stepwise regression. Approximately 60% to 70% of the variation
      in each of the scores was explained by five to seven different HOPES problem
      statements, with a single item explaining 47% to 59% of the variation. We created
      illustrative profiles for each of the three MOS-HIV scales using the HOPES items
      identified in the regressions. Independent of the scale, persons scoring in the
      top MOS-HIV quartile tended to report few if any problems, whereas a decline in
      score to the next quartile was characterized by functional difficulties (e.g.,
      "HIV interferes with work"). The onset of specific problems might trigger further
      evaluation and potential intervention from health care providers to help maintain
      patient functioning.

PMID- 9562047
TI  - Transforming laboratory test results to improve clinical outcome predictions in
      HIV patients. Swiss HIV Cohort Study.
AB  - Transforming natural units of laboratory markers of HIV disease may improve their
      ability to predict clinical outcomes. The authors examined this issue within a
      prospective study of 394 patients enrolled in the Swiss HIV Cohort Study (SHCS)
      between 1991 and 1993. Baseline predictors included CD4+ and CD8+ cell counts,
      HIV RNA levels, beta2-microglobulin, and age. Outcomes were death and clinical
      progression. A range of power transformations was applied to each predictor, and
      the goodness-of-fit of the corresponding proportional hazards models was
      assessed. The prognostic value of all laboratory variables could be improved on
      by power transformations. To predict either outcome variable, the "best"
      transformation of HIV RNA copies and CD8+ cell counts was the logarithm; for
      beta2-microglobulin, it was power -2. For CD4+ cell counts, the best
      transformation depended on the outcome variable: it was power 0.2 when predicting
      survival, and power 0.4 when predicting clinical progression. The single best
      predictor variable was the ratio of HIV RNA copies per CD4+ cell, for both death
      (logarithmic transformation) and clinical progression (power -0.1
      transformation). Natural units of laboratory variables are not optimal for the
      prediction of clinical events in HIV-infected patients. Which transformation is
      best depends on the predictor under consideration.

PMID- 9562048
TI  - Conservation of total T-cell counts during HIV infection: alternative hypotheses
      and implications.
AB  - While CD4+ T-cell counts in the blood of HIV-infected individuals gradually
      decrease, there is a parallel increase in the number of blood CD8+ T cells such
      that the total number of T cells remains essentially constant for several years
      (1). The basis and significance of this phenomenon are not known. Based on a
      statistical analysis of longitudinal T-cell counts from the Transfusion Safety
      Study (TSS) database and on theoretical considerations, we evaluate several
      alternative models, including versions of the "blind homeostasis" (BH) hypothesis
      (1-3). At issue is the nature of the homeostatic regulation of lymphocytes and
      its apparent failure in HIV infection. The most plausible explanation for the
      conservation of total blood T-cell numbers while subset ratios change is that
      CD4+ and CD8+ T cells compete for a limited access to the blood compartment. Such
      interaction between the subsets implies, in particular, that changes in the
      number of CD4+ T cells occurring in other tissues cannot be reliably inferred
      from those observed in the blood. We reiterate propositions made earlier (4) that
      much of the apparent "depletion" of CD4+ lymphocytes during the asymptomatic
      phase of HIV infection may be attributed to redistribution between the tissues
      and the blood compartment.

PMID- 9562049
TI  - Endemic infection with HTLV-IIB in Venezuelan Indians: molecular
      characterization.
AB  - The peripheral blood of 41 Yaruro and Guahibo Indians from Venezuela was examined
      for HTLV antibodies and DNA. Twenty-five samples (61%) were found to be infected
      with HTLV-IIB. The sensitivities of the serologic and DNA polymerase chain
      reaction (PCR) analyses were 80% and 96%, respectively. Epidemiologic studies
      supported both sexual and perinatal transmission of the virus. Sequence analyses
      of the HTLV-IIB strains from these Indians indicate that they are unique relative
      to HTLV-II detected in other groups of humans. HTLV-IIB-G2 isolated from a
      Guahibo Indian is the most divergent HTLV-IIB strain relative to the prototype
      HTLV-II NRA.

PMID- 9562050
TI  - HIV incidence in Ethiopian immigrants to Israel.
AB  - The HIV incidence in recent adult Ethiopian immigrants to Israel is estimated
      through the use of snapshot estimators based on percentage of CD4 progression
      with time since infection, whereas the preimmigration incidence experienced by
      this population is estimated using an epidemic model applied to HIV prevalence
      data obtained from immigrants on arrival in Israel. The snapshot estimators place
      incidence in adult Ethiopian immigrants in Israel between 3 and 11
      infections/1000 uninfected persons/year around May 1995. In contrast, the
      epidemic model suggests that the incidence experienced by this population before
      immigration was between 12 and 22 infections/1000 uninfected persons/year.
      Although the drop in incidence postimmigration is good news, in the aggregate, we
      estimate that between 50 and 190 new infections have occurred annually in adult
      Ethiopians who have immigrated to Israel.

PMID- 9562051
TI  - HIV counseling and testing: behavior and practices of women of childbearing age
      in Abidjan, Cote d'Ivoire. DYSCER-CI Group.
AB  - We assessed factors associated with women's attitudes toward HIV test results in
      gynecology clinics in Abidjan, Cote d'Ivoire. HIV testing was systematically
      offered to nonpregnant women attending two gynecology clinics in Abidjan.
      Individual pretest counseling was performed by trained midwives. Posttest
      counseling was given 2 weeks later to women who wished to know their HIV test
      results. HIV testing was offered to a total of 1482 women, of whom 1401 (94.5%)
      agreed to be screened. The prevalence of HIV infection was 21.3%. Of the women
      who participated, 10% failed to return. Youth, low educational level, and absence
      of genital infection were findings individually associated with failure by
      participants to return for their test results. Among the 1242 women who returned,
      13.7% did not wish to know the results of their HIV test. A positive HIV test
      result, being native to Cote d'Ivoire, a high educational level, and knowing the
      existence of the asymptomatic stage of HIV infection were factors independently
      associated with declining to know the HIV test result. In conclusion, women who
      declined to know their HIV test results presented a specific profile at the time
      of HIV testing. This information can be used to improve pretest counseling and
      the efficacy of future HIV screening programs.

PMID- 9562052
TI  - How can the health care costs be suppressed in widespread use of expensive MR
      units? A Japanese experience.

PMID- 9562053
TI  - Status of MRI in Australia.

PMID- 9562054
TI  - Neuroimaging in epilepsy.
AB  - Neuroimaging techniques have improved the understanding, diagnosis, and
      management of epilepsy. By providing excellent structural information, MRI is the
      technique of choice in evaluating patients with epilepsy. Functional imaging
      techniques, including MR spectroscopy, functional MRI, positron emission
      tomography, and single photon emission CT, permit noninvasive assessment of the
      epileptic substrate, its functional status, and neuroreceptors. The MRI-based
      techniques will potentially assume a greater role in the cost-effective workup of
      the patient. Currently, newer techniques such as magnetoencephalography, magnetic
      source imaging, and optical imaging are research tools.

PMID- 9562055
TI  - III. New developments: 2. Virtual MR endoscopy in the central nervous system.
AB  - Recent advances in three-dimensional (3D) data acquisition and postprocessing
      technologies have been playing a important role in widening the potential
      applications of 3D display. The authors described new applications of a virtual
      endoscopic algorithm for 3D display of high resolution MR images: (a)
      intracranial intravascular virtual MR endoscopy using the 3D fast imaging with
      steady state precession (FISP) sequence, and (b) virtual MR endoscopy of the
      cerebrospinal fluid (CSF) spaces using the constructive interference in steady
      state (CISS) three-dimensional Fourier transform (3DFT) sequence. The virtual
      endoscopic images were displayed with use of a commercially available perspective
      volume-rendering algorithm. Our initial experience showed that virtual MR
      endoscopy can be performed to observe the intracranial arteries and CSF spaces
      from the viewpoints within themselves. Although the clinical use of the
      intracranial virtual MR endoscopy has not been established yet, the images
      obtained are very attractive and further investigations in this field will be
      expected.

PMID- 9562056
TI  - MRI of CNS parasitic diseases.
AB  - This article reviews MRI findings of parasitic diseases of the central nervous
      system (CNS), with emphasis on neurocysticercosis, which is by far the most
      common CNS parasitic infection worldwide. MRI findings of neurocysticercosis are
      various, depending on the location (parenchymal, cisternal, ventricular, and
      spinal forms), and temporal evolutional stages (vesicular, colloid vesicular,
      granular nodular, and nodular calcified stages) of the worm. Classical findings
      of each location and stage are presented. Characteristic MRI findings of cerebral
      toxoplasmosis frequently seen in patients with acquired immunodeficiency syndrome
      (AIDS), paragonimiasis, and sparganosis that have most commonly been reported in
      East Asia are also illustrated. MRI is superior to CT scan in the evaluation of
      most CNS parasitic infections and is nearly diagnostic, particularly in endemic
      areas. Contrast-enhanced study is essential not only for specific diagnosis of
      the disease, but also for assessment of the inflammatory activity.

PMID- 9562058
TI  - Fukuyama congenital muscular dystrophy: a neuroradiologic review.
AB  - We reviewed neuroradiologic findings of Fukuyama congenital muscular dystrophy
      (FCMD) and correlated them with the known neuropathology. All patients showed
      thick and bumpy cortices with shallow sulci corresponding to polymicrogyria, and
      approximately half of the patients showed pachygyric cortex with smooth surface
      corresponding to type II lissencephaly. The two types of cortical dysplasias
      presented characteristic distributions: the former demonstrated frontal lobe
      involvement in all and parietotemporal lobe involvement in some, whereas the
      latter involved the temporo-occipital lobes. Most patients showed prolonged T1
      and T2 signal in the white matter, which was indistinct in neonates and
      infrequently seen in adolescents. Cerebellar polymicrogyria depicted as
      disorganized cerebellar foliation accompanying cysts were found more than 90% of
      the patients. In conclusion, brain MRI demonstrates findings consistent with the
      known neuropathology of FCMD. The detection of the two types of cerebral cortical
      dysplasia with characteristic distribution and cerebellar abnormalities is
      helpful in the differential and early diagnosis.

PMID- 9562057
TI  - MR findings of Minamata disease--organic mercury poisoning.
AB  - We describe MR findings in patients with Minamata disease who have been followed
      for a long time. All patients examined were affected after daily eating of a
      large quantity of methylmercury-contaminated seafood, from 1955 to 1958, and
      showed typical neurological findings. On MR images, the visual cortex, the
      cerebellar vermis and hemispheres, and the postcentral cortex are significantly
      atrophic in Minamata disease. The visual cortex is slightly hypointense on T1
      weighted images and hyperintense on T2-weighted images, probably representing the
      pathologic changes of status spongiosus. MRI can demonstrate the lesions located
      in the calcarine area, cerebellum, and postcentral gyri, which are probably
      related to three of the characteristic manifestations of this disease: the
      constriction of the visual fields, ataxia, and sensory disturbance, respectively.

PMID- 9562059
TI  - MRI of nasopharyngeal carcinoma with emphasis on relationship to radiotherapy.
AB  - MRI has been used increasingly in the evaluation of nasopharyngeal carcinoma
      (NPC) because of its good tissue contrast and multiplanar capacity. Although
      there are some controversies in assessing skull base invasion and cervical
      metastatic adenopathy, recent reports demonstrate that MRI is currently better
      than or as good as CT in defining the extent of NPC. During follow-up of patients
      with NPC after radiotherapy, MRI is also more effective than CT in demonstrating
      tumor recurrence and in detecting postradiation complications. However, the
      difficulty of using MRI to detect early mucosal recurrence and to differentiate
      postradiation tissue changes from local tumor recurrence should be recognized.
      This paper reviews the literature regarding MRI of NPC related to radiotherapy,
      with special emphasis on treatment planning, recurrence assessment, and
      complication detection.

PMID- 9562060
TI  - MRI of the liver.
AB  - MRI of the liver is a powerful imaging modality for detection and
      characterization of liver pathology. MRI technology continues to evolve with
      developments in scanner hardware performance and refinements in imaging
      sequences, particularly in respect to fast imaging techniques, improving the
      quality of images that can be routinely achieved. Fast imaging techniques allow
      dynamic contrast-enhanced scanning to assist in lesion detection and
      characterization. An array of tissue-specific contrast agents are also becoming
      available; the clinical utility of some of these agents is yet to be fully
      established. An overview of scanning technique, contrast media, and the role of
      MRI in liver lesion detection and characterization is presented, with a review of
      the typical imaging characteristics of common focal and diffuse hepatic diseases.
      Where possible, emphasis has been placed on features that allow distinction
      between the various pathologic entities described.

PMID- 9562061
TI  - Hepatitis, cirrhosis, and hepatoma.
AB  - Virus hepatitis and liver cirrhosis are found at high incidence in Asia, and they
      require not only biochemical examination of blood but also subsequent imaging,
      because they are often complicated by hepatocellular carcinoma (HCC). It is,
      therefore, very important to know the specific appearances of hepatitis, liver
      cirrhosis, and HCC when we diagnose these diffuse liver diseases. Liver necrosis
      due to severe hepatitis is seen as high intensity on T2-weighted spin echo
      images. Regeneration is seen as low intensity on T2-weighted images. Morphologic
      and pathologic changes of cirrhotic liver are well demonstrated by MR imaging
      techniques. Fibrotic septum with inflammatory cell infiltration or rich pseudo
      bile duct show high intensity on T2-weighted images, and regenerating nodules
      shows low intensity. Gradient echo images show regenerating nodules with iron
      deposition as low-intensity nodules due to susceptibility artifact. MRI also has
      the potential to evaluate function of diffuse liver disease, cirrhosis, and
      hepatitis. MRI can visualize and diagnose HCC objectively. Dynamic MRI is very
      useful for diagnosing HCC. It is also applied for evaluation of effect after
      transcatheter arterial chemoembolization, because it shows enhancement only in
      the viable region at an arterial phase. MRI is less invasive and is thus an
      extremely important form of liver imaging.

PMID- 9562062
TI  - MRI of clonorchiasis and cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinomas are usually categorized as peripheral
      cholangiocarcinoma or hilar cholangiocarcinoma on the basis of the site of
      origin. Clonorchiasis is a trematodiasis caused by chronic infestation of liver
      flukes, which are largely confined to the Orient, from Japan to Vietnam. The
      close relationship between clonorchiasis and cholangiocarcinoma has long been
      emphasized. This paper discusses the efficacy and possible roles of MRI for
      imaging clonorchiasis and cholangiocarcinoma of the liver. Although sonography,
      CT, and direct cholangiography have been used traditionally to diagnose these
      diseases, the role of MRI has been increasing rapidly with dramatic progress of
      the MRI techniques. We review MRI findings of clonorchiasis and
      cholangiocarcinoma and discuss the potential usefulness of MRI.

PMID- 9562063
TI  - Ultrafast MR imaging of the abdomen: echo planar imaging and diffusion-weighted
      imaging.
AB  - Ultrafast MRI technique has become available with the introduction of new
      generation MR scanners for abdominal imaging. However, there is no consensus
      about the optimal imaging acquisition at the present time. Because single shot
      echo planar imaging (EPI) technique is based on high technology and had just
      applied in clinical imaging, further clinical investigation will be needed.
      Currently, the hypersensitivity to magnetic inhomogeneity and local magnetic
      susceptibility and the low spatial resolution may limit the widespread
      application of EPI technique. In addition to providing information for
      morphologic diagnosis, EPI will be more widely used for functional and
      qualitative diagnosis. Diffusion-weighted imaging can be used for differentiation
      of solid tumors according to their different cellular construction, evaluation of
      cystic lesions based on the different viscosity of their contents, and assessment
      of diffused pathologic changes in the parenchyma of solid organs. In addition to
      the previous parameters such as proton density and T1 and T2 values, diffusion
      factors may provide important information for the qualitative and dynamic
      evaluation of abdominal pathologic changes. Even though there are many
      difficulties that must be solved for diffusion-weighted imaging, a more wide
      application of this technique is expected through technologic improvement.

PMID- 9562064
TI  - Application of MRI for small intestinal diseases.
AB  - Until recently, MRI has not been considered to be suitable for the evaluation of
      the small intestine due to artifacts associated with bowel peristalsis or
      respiration. However, recent advances of MR techniques enable the acquisition of
      clear images of the small intestine. Therefore, the purpose of this article is to
      review the details for the application of MRI in patients with small intestinal
      diseases. This article discusses bowel preparation and oral contrast agents as
      well as MR techniques and pulse sequences. Thereafter, the usefulness of MRI for
      the lesions in the peritoneal cavity or in the gastrointestinal tract are
      discussed. Small intestinal lesions are categorized into inflammatory,
      neoplastic, ischemic, and obstructive bowel diseases. In conclusion, MRI can be
      used as an alternate modality of choice for imaging various diseases of the small
      intestine.

PMID- 9562065
TI  - Ultrafast T2-weighted imaging of the abdomen and pelvis: use of single shot fast
      spin-echo imaging.
AB  - Single shot (SS) rapid acquisition with relaxation enhancement (RARE) and half
      Fourier SS-RARE (HFSS-RARE, HASTE, or SS-FSE) sequences allow ultrafast imaging
      acquisition and generate high imaging quality. Images can be acquired within a
      very short time, without artifacts from physiologic motion. They are widely
      applied in the abdominal MRI. Clinical application of the ultrafast SS-RARE
      imaging techniques provide not only improved temporal resolution but better
      spatial resolution, higher SNR, and higher tissue contrast. Imaging parameters
      must be optimized for different MR scanners to obtain diagnostic images.

PMID- 9562066
TI  - Cervical cancer.
AB  - The stage estimated by clinical FIGO staging is the main determinant in guiding
      the treatment decisions. However, clinical FIGO staging does have inherent
      inaccuracies, because it does not include significant prognostic factors.
      Presently, MRI is not officially incorporated in the staging workup system;
      however, it is widely accepted as the most reliable imaging modality in
      evaluating cervical cancer and in treatment planning. MRI offers direct tumor
      visualization, accurate assessment of the depth of stromal invasion and tumor
      volume, lymph node evaluation, and reliable staging accuracy. Published reports
      show the superiority of MRI over clinical staging, and several recent works on
      dynamic MRI suggest further improvement of MRI in evaluating cervical cancer.

PMID- 9562067
TI  - Ossification of posterior longitudinal ligaments: evaluation with MRI.
AB  - Ossification of the posterior longitudinal ligament is a special subcategory of
      degenerative disease responsible for compression of the spinal cord. On MR
      images, T2-weighted sequences are the most effective to evaluate both spinal cord
      compression due to the ossification and abnormal signal intensity of the cord.
      Although ossification of the ligaments is well demonstrated on CT and plain
      radiographs, MRI noninvasively provides useful information about the degree and
      extent of spinal cord compression, as well as the character of the ossification.

PMID- 9562068
TI  - Takayasu arteritis: MR manifestations and diagnosis of acute and chronic phase.
AB  - Diagnosis of Takayasu arteritis is difficult because the clinical features are
      similar to those of other diseases. In the late occlusive or pulseless phase
      Takayasu arteritis, angiography usually demonstrates luminal changes such as such
      as stenosis, occlusion, or aneurysmal dilatation of the aorta and pulmonary
      artery and of their branches. However, absence of such luminal changes does not
      exclude the possibility of early or systemic phase Takayasu arteritis. Cross
      sectional scanning such as CT scan and MRI plays an important role in
      demonstrating arterial wall changes in the early diagnosis of Takayasu arteritis.
      Improvement in the clinical findings and subsidence of the active inflammatory
      process can be expected with early steroid treatment. The common and uncommon MR
      appearances of the late occlusive phase and the recently described radiographic
      features of the early systemic phase are illustrated.

PMID- 9562069
TI  - Application of MR in stereotactic radiosurgery.
AB  - Radiosurgery, a bladeless brain surgery without opening skull, requires higher
      imaging accuracy as compared to microsurgery. Accordingly, we must refine the
      ways we use the MR scanner and interpret the obtained images. A well tuned and
      regularly calibrated MR scanner provides excellent images, which allow us to
      define detailed intracranial structures without distortion. This enables us to
      obtain a reliable imaging diagnosis despite the fact that pathologic diagnosis is
      not available in many radiosurgical patients. Due to its three-dimensional
      imaging and excellence in tissue and spatial contrast, MR is important in
      exploring new radiosurgical indications. Large arteriovenous malformations (AVM),
      dural AVM of cavernous sinus and trigeminal neuralgia are some of the successful
      examples. By using MR, longitudinal investigation of radiosurgical effects
      becomes feasible. For tumors, the longitudinal studies are important in
      optimization of dose selection. For AVM, MR is reliable in verification of
      radiosurgical result. The reliability is comparable to conventional x-ray
      angiography. Application of MR enhances the essence of noninvasiveness of
      radiosurgery.

PMID- 9562070
TI  - Standard dose Gd-DTPA dynamic MR of renal arteries.
AB  - Renal MR contrast enhancement depends on the timing of image acquisition. Limited
      human trials have demonstrated efficacy of renal artery stents on salvage of
      renal function. This study assessed the ability of dynamic gadolinium
      diethylenetriamine pentaacetic acid (Gd-DTPA) administration to demonstrate renal
      artery stenosis and renal stent patency compared to conventional angiography as
      the gold standard. Twenty subjects referred for renal angiography underwent 22
      dynamic MR studies, including 7 with renal artery stenting (Palmaz P204 or P201,
      Johnson & Johnson, Sydney, Australia). All were examined with conventional
      angiography and after dynamic Gd-DTPA infusion. Coronal MR images of the kidneys
      were acquired using a GE Signa 1.5-T magnet (General Electric Medical Systems,
      Milwaukee, WI) (fast spoiled gradient echo [FSPGR]; TE=4.2 msec, TR=68-150 msec,
      flip angle=75 degrees) 0 to 600 seconds after iv bolus injection of 15 ml of Gd
      DTPA during sequential breath-hold acquisitions, 13 to 32 seconds each. All 51
      renal arteries (13 stenosed, 38 normal) were detected with dynamic MRI. Severity
      of renal artery stenosis was classified correctly with an accuracy of 98% (95%
      confidence interval [CI]: 85-100), yielding 98% specificity and 100% sensitivity.
      All nine renal stents were visualized with 100% accurate patency documentation.
      FSPGR MRI with bolus Gd-DTPA administration can provide adequate time and spatial
      resolution to demonstrate renal artery stenosis.

PMID- 9562071
TI  - The value of detection of flow voids between the uterus and the leiomyoma with
      MRI.
AB  - Flow voids are occasionally seen between the uterus and the leiomyoma. This study
      was performed to determine the prevalence of this sign and its relation to tumor
      size and location, internal signal intensity of the leiomyomas, and the ease of
      detectability using different MR sequences. Also, to understand the pathologic
      causes for the phenomenon of flow voids. The MR images of the pelvis in 92
      females with 359 uterine leiomyomas were analyzed. Flow voids located between the
      uterus and the leiomyomas were seen in 32 lesions on T1-weighted images and in 12
      on T2-weighted images. Flow void was seen exclusively in leiomyomas of 3-cm
      diameter or larger. In five pedunculated subserous leiomyomas, flow voids were
      seen within the pedicle of the tumor. Large leiomyomas and leiomyomas with
      irregular signal intensity on T2-weighted images showed significantly greater
      frequency of signal void than other leiomyomas (P < .01). The sign was not seen
      in any other pelvic tumors. On pathologic evaluation, the flow voids were found
      to correspond to dilated feeding arteries located outside the capsule of the
      leiomyoma.

PMID- 9562072
TI  - Comparison of breath-hold multishot echo-planar and respiratory triggered fast
      spin-echo sequences for T2-weighted MRI of liver lesions.
AB  - The purpose of this study was to evaluate the usefulness of multishot echo-planar
      imaging in detecting liver tumors in comparison with respiratory triggered T2
      weighted fast-spin-echo (FSE) imaging. Thirty-two patients with 70 focal liver
      lesions were imaged using a 1.5-T high speed MR imager. Eight-shot echo-planar
      images covering the whole liver were acquired during a single breath-hold period.
      FSE images were acquired with respiratory triggering in approximately 4 minutes.
      Lesion detectability and image quality of the two pulse sequences were analyzed
      qualitatively. Quantitative analysis was performed by means of signal-to-noise
      and tumor-liver contrast-to-noise analysis. Lesion detectability was comparable
      in both solid (86.3% vs 90.2%: .3 < P < .5) and nonsolid lesions (89.5% vs 100%:
      .3 < P < .5) between echo-planar and FSE images. Echo-planar imaging provided
      significantly reduced image artifact, better lesion conspicuity, and anatomic
      detail compared with FSE imaging. The signal-to-noise and contrast-to-noise
      ratios of echo-planar images were significantly higher than those of FSE images.
      Breath-hold eight-shot echo-planar imaging can be an alternative to T2-weighted
      FSE imaging because it can provide comparable image quality in a substantially
      decreased acquisition time.

PMID- 9562073
TI  - Characterization of focal liver lesions with half-fourier acquisition single-shot
      turbo-spin-echo (HASTE) and inversion recovery (IR)-HASTE sequences.
AB  - The half-Fourier acquisition single-shot turbo-spin-echo (HASTE) sequence allows
      for heavily T2-weighted images, and the inversion recovery (IR)-HASTE sequence
      represents the T1 value of the tissue in a very short time. This study was
      undertaken to determine whether characterizing focal liver lesions can be made by
      combination with these very fast sequences. Seventy-four patients (33 cysts, 28
      hemangiomas, and 33 malignant solid liver masses [15 metastatic tumors, 14
      hepatocellular carcinomas, and 4 cholangiocarcinomas) underwent dynamic CT and
      breath-hold abdominal MRI using turbo-spin-echo (TSE), HASTE, and IR-HASTE
      sequences with variable T1 values on a 1.5-T MR unit. The imaging time for each
      slice was 2 seconds for HASTE imaging and 2 to 4 seconds for IR-HASTE imaging.
      Lesion detection and qualitative characterization were evaluated. Quantitative
      analysis was performed by measuring the contrast-to-noise ratios (CNRs) as well
      as visual analysis. The inversion time (TI) nulling values were also
      statistically analyzed. All cystic lesions were detected on both TSE and HASTE
      imagings. For solid lesions, TSE failed to detect one small solid lesion and
      HASTE sequence failed to detect three lesions. With HASTE sequences, all cysts
      and hemangiomas were markedly hyperintense in comparison with malignant solid
      masses. CNRs of hemangiomas or cysts were significantly higher than those of
      malignant solid masses (P < .01), and there was no overlap. The TI nulling value
      was 1,100+/-100 msec for hemangiomas, 1,900+/-110 msec for cysts, and 740+/-140
      msec for malignant solid masses. There was no overlap between the TI nulling
      values of hemangiomas and cysts (P < .01). By combining the CNR from the HASTE
      sequence and the TI nulling value from the IR-HASTE sequence, complete
      discrimination among malignant solid masses, hemangiomas, and cysts of the liver
      could be made. Application of HASTE (representing T2 values) and IR-HASTE
      (representing T1 values) sequences provided a rapid and reliable imaging method
      for characterizing focal liver lesions without the use of contrast medium.

PMID- 9562074
TI  - Enhancement of phase-contrast MR angiography with superparamagnetic iron oxide.
AB  - The effect of superparamagnetic iron oxide particles (AMI-227) was assessed in
      three-dimensional (3D) phase-contrast (PC) MR angiography (MRA), with various
      scanning parameters for rats at 1.5 T. The blood T1 and T2 before and after 20
      micromol Fe/kg of AMI-227 injection were measured sequentially at .47 T. The
      visualization of abdominal aorta, renal artery, inferior vena cava, and portal
      vein was respectively evaluated before and after AMI-227 injection qualitatively
      by the four confidence levels and quantitatively by analysis of signal-to-noise
      ratio (SNR) of vessels. The blood T1 and T2 were sufficiently shortened for at
      least 1 hour after AMI-227 injection. The visualization of each vessel was
      improved by AMI-227 at various velocity encoding (VENC) value, suggesting the
      extended application of PC-MRA in various conditions. The optimal flip angle was
      increased from 20 degrees to 30 degrees in higher VENC after AMI-227 injection,
      resulting in higher signal from blood flow. Quantitative analyses showed that the
      optimal flip angle to achieve the maximum SNR seemed to be 20 degrees in
      unenhanced images, but the optimal flip angle of the high speed flow was
      increased by contrast enhancement. The postcontrast PC-MRA provides the increased
      sensitivity of slow flow components, even with a high VENC gradient. AMI-227 can
      significantly improve SNR to blood vessels during 3D-PC-MRA with various scanning
      parameters.

PMID- 9562075
TI  - Microwave coagulation therapy on hepatomas: CT and MR appearance after therapy.
AB  - Laparoscopic microwave coagulation (LMC) for hepatocellular carcinomas (HCCs) was
      performed on 26 HCCs in 17 patients. Contrast-enhanced CT (CECT) and MR images
      (T1-weighted imaging [T1WI], T2WI, gadolinium-diethylenetriamine pentaacetic acid
      [Gd-DTPA] T1WI) were obtained to determine changes over time. The irradiated
      center exhibited low to moderate intensity with surrounded high intensity (HI) on
      T2WI and Gd-DTPA T1WI. On T1WI, lesions showed four patterns of intensity:
      uniform HI (30.8%), arcuate HI (26.9%), mainly low with spot HI (30.8%), and
      isointensity to hypointensity (11.5%). Follow-up imaging at more than 170 days
      revealed isointensity to hypointensity on T1WI (96.2%) and reduced HI on T2
      weighted imaging (T2WI) and Gd-DTPA T1WI. All lesions became less conspicuous and
      were reduced in volume. HCC shows time-related changes in signals and size after
      LMC. Identifying the irradiated lesion is necessary to estimate the adequacy of
      treatment by comparison with the pretherapeutic image.

PMID- 9562076
TI  - Improvement of MR cholangiopancreatography at .5 T: three-dimensional half
      averaged single-shot fast spin echo with multi-breath-hold technique.
AB  - The purpose of this study was to determine the advantage of a three-dimensional
      (3D) single-shot fast-spin-echo (SSFSE) sequence to obtain MR
      cholangiopancreatography (MRCP) with a .5-T MR unit by comparison with a two
      dimensional (2D) SSFSE sequence. MRCP with 2D-SSFSE and with 3D-SSFSE with 128
      echo train lengths was performed on 15 volunteers and 38 patients with
      pancreatobiliary disease using a .5-T MR unit. For maximum intensity projection
      (MIP) reconstruction, the section thickness of source images was 4 mm in the 2D
      SSFSE and 3 mm in the 3D-SSFSE. 3D volume data in 3D-SSFSE were obtained using
      repeated short breath-hold of 2 seconds for every repetition time throughout the
      examination. The image quality, duct conspicuity, signal-intensity ratio (SIR),
      and contrast-to-noise ratio (CNR) were evaluated. In 23 of the patients who
      underwent both MRCP and direct cholangiopancreatography (endoscopic retrograde
      cholangiopancreatography [ERCP]/percutaneous transhepatic cholangiography [PTC]),
      a comparison between these two modalities was also conducted. The image quality
      of the MIP image with 3D-SSFSE (49 of 53, 92.5% graded excellent or good) was
      superior to that with 2D-SSFSE (31 of 53, 58.4%). Duct conspicuity, SIR, and CNR
      were significantly higher with 3D-SSFSE than with 2D-SSFSE. 3D-SSFSE also showed
      a stronger relationship with the ERCP/PTC findings compared to 2D-SSFSE. 3D-SSFSE
      provided satisfactory quality, SIR, and CNR of MRCP images, even when a .5-T MR
      unit was used, because the breath-hold technique used during 3D data sampling
      minimized all types of motion effects.

PMID- 9562077
TI  - Reproducibility study of left ventricular measurements with breath-hold cine MRI
      using a semiautomated volumetric image analysis program.
AB  - The reproducibility of a semiautomated method of volumetric analysis allowing
      estimates of left ventricular (LV) parameters in approximately 5 minutes of
      analysis time is reported. Twenty normal volunteers underwent cine breath-hold
      cardiac MRI on two occasions with two observers using this new semiautomated
      method to estimate LV parameters. Reproducibility of this technique was
      comparable to published data with a variability of less than approximately 10%
      for all LV parameters calculated. Using this technique, the 95% confidence limits
      for change for left ventricular end diastolic volume (LVEDV) = +/-15 ml, left
      ventricular end systolic volume (LVESV) = +/-8 ml, LV mass = +/-24 g, and left
      ventricular ejection fraction (LVEF) = +/-6%. This new method also compared
      favorably to established manual methods. This new method permits estimation of LV
      parameters with acceptable reproducibility in a time that may permit routine
      quantitation of cardiac MR studies.

PMID- 9562078
TI  - Measurement of magnetization transfer in different stages of neurocysticercosis.
AB  - The purpose of this study was to establish magnetization transfer ratio (MTR) in
      different stages of neurocysticercosis. A total 2,532 cysticerci were studied
      prospectively in 15 cases. MTR from different regions of the lesions (ie, the
      cyst, the protoscolex or mural nodule, the granuloma wall) were calculated in
      different stages of evolution/degeneration in all cases. Of a total 2,532 lesions
      studied, 2,261 (89.29%) were seen on routine spin-echo (SE) imaging. The rest of
      the lesions were only seen on magnetization transfer (MT) SE imaging. Maximum MTR
      was calculated from healing lesions (mean + SD = 31.0+/-2.8) and from the core of
      SE invisible lesions (30.0+/-5.1). Innocuous cystic lesions, which were
      hyperintense on T2-weighted images, did not show any MT (MTR = 5.10+/-1.2),
      whereas degenerating T2 hyperintense lesions showed MTR of 26.40+/-2.7.
      Nondegenerating and degenerating scolices showed an intermediate MTR of 21.7+/
      3.3 and 15.0+/-4.5, respectively. MT varies between different parts of the lesion
      and also from the same part in different stages of evolution/degeneration of the
      lesion. The visibility of a lesion on MT-SE sequence was dependent on its MTR and
      its location at a particular site (cortical gray matter, white matter, or deep
      gray matter). The difference in MTR of the lesion and the surrounding brain
      parenchyma decides the resulting contrast and visibility of the lesion.

PMID- 9562079
TI  - A reproducible method for automated extraction of brain volumes from 3D human
      head MR images.
AB  - An automated method for extracting brain volumes from three commonly acquired
      three-dimensional (3D) MR images (proton density, T1 weighted, and T2-weighted)
      of the human head is described. The procedure is divided into four levels:
      preprocessing, segmentation, scalp removal, and postprocessing. A user-provided
      reference point is the sole operator-dependent input required. The method's
      parameters were first optimized and then fixed and applied to 30 repeat data sets
      from 15 normal older adult subjects to investigate its reproducibility. Percent
      differences between total brain volumes (TBVs) for the subjects' repeated data
      sets ranged from .5% to 2.2%. We conclude that the method is both robust and
      reproducible and has the potential for wide application.

PMID- 9562080
TI  - Throwing injury of the elbow: assessment with gradient three-dimensional, fourier
      transform gradient-echo and short tau inversion recovery images.
AB  - We assessed MR findings of throwing injuries occurring in the elbow joint using
      three-dimensional Fourier transform (3DFT) and short tau inversion recovery
      (STIR) images. MR images of 63 elbows in 63 male patients aged from 10 to 32
      years (mean age, 15 years 11 months) suffering from throwing injury were visually
      analyzed. The sequences used for the study were axial 3DFT and coronal STIR. Full
      thickness tears were demonstrated in 34 elbows and undersurface tears of the
      ulnar collateral ligament (UCL) were demonstrated in five elbows. Thirty loose
      bodies were detected in 14 elbows. Cartilaginous damage due to osteochondral
      injury was depicted in 21 elbows. Multiplanar reformatted images using the 3DFT
      data set were useful for assessing torn UCLs, intraarticular loose bodies, and
      capitellar fragments. Full-thickness tears and undersurface tears of the UCL
      could be differentiated with STIR images. 3DFT and STIR sequences depict various
      aspects of throwing injuries occurring in the elbow.

PMID- 9562081
TI  - Tissue temperature monitoring with multiple gradient-echo imaging sequences.
AB  - The inherent sensitivity of multiple gradient-echo sequences to the chemical
      shift is exploited to rapidly map muscle water frequency shifts caused by
      ultrasonic heating. The use of multiple echoes is shown to offer several
      advantages over single gradient-echo approaches previously proposed for
      temperature measurement. An increase in the effective bandwidth significantly
      reduces aliasing problems observed with single gradient-echo methods in high
      temperature applications. Of greater significance is the improved immunity to
      intrascan motion found for multi-echo versus single echo gradient methods, making
      the former more attractive for clinical applications. Finally, a sensitivity to
      the presence of multiple spectral components unavailable with single gradient
      echo methods is obtained.

PMID- 9562082
TI  - Biliary cystadenoma with mesenchymal stroma of the liver: correlation between
      unusual MR appearance and pathologic findings.
AB  - We reported a case of the biliary cystadenoma of the liver. The cystic mass had
      lobulation and septation and showed marked hyperintensity on T1-weighted images
      and hypointensity on T2-weighted images; MR findings were very unusual for
      cystadenoma. The content of the cystic mass was jelly-like, thick mucinous fluid
      without intracystic hemorrhage. We concluded that these unusual signal
      intensities of the cyst were due to hyperproteinous mucinous fluid.

PMID- 9562083
TI  - A novel MR angiography technique: SPEED acquisition using half-Fourier RARE.
AB  - A novel MR angiography (MRA) method, swap phase encode extended data (SPEED), was
      developed. Two one-shot images with the phase-encode directions swapped were
      collected within a single breath-hold period and processed with a maximum
      intensity projection (MIP) to obtain an image. In this study, a long echo train
      two-dimensional rapid acquisition with relaxation enhancement (RARE) sequence
      with half-Fourier (half-RARE) was used to obtain the pulmonary MRA images. The
      MIP image obtained using the SPEED technique presented promising results for
      pulmonary vessels.

PMID- 9562084
TI  - Dynamic MRI of transcorneal dispersion of oxygen into the anterior chamber of
      human eye.
AB  - To measure the transcorneal dispersion of oxygen into the anterior chamber,
      dynamic T1-weighted fast-spin-echo MRI (TR=2 seconds, TE=15 msec, 5-mm slice) of
      the human eye was performed both before and during oxygen supply to a full goggle
      placed on the face. During the course of the imaging, a significant increase in
      the signals in the anterior chamber occurred. This indicated that transcorneal
      dispersion of oxygen into the anterior chamber can be evaluated by this
      procedure, suggesting that this method may be useful for diagnosing dysfunction
      of the cornea or aqueous flow.

PMID- 9562085
TI  - Effect of carbogen, oxygen and intraocular pressure on Heidelberg retina
      flowmeter parameter 'flow' measured at the papilla.
AB  - The aim of the study was to evaluate whether the Heidelberg retina flowmeter
      (HRF), a new device for retinal and anterior optic nerve blood flow assessment,
      can gauge, at least semiquantitatively, a known effect such as an increase in
      optic nerve blood flow by hypercapnia or a decrease in optic nerve blood flow by
      hyperoxia or high intraocular pressure (IOP). Measurements with the HRF were
      obtained at the papilla of three groups of 5 young healthy subjects (1) at
      baseline and after breathing 5% carbogen, (2) at baseline and after breathing
      100% oxygen and (3) at baseline and after increasing IOP to 20 and 50 mm Hg. The
      changes in the value of the HRF parameter 'flow' were analyzed by means of a
      paired Student's t test. Breathing 100% oxygen for 7 min resulted in a
      statistically significant decrease of 34.7+/-2.5% (mean+/-SEM) in HR parameter
      'flow' (p < 0.01) at the papilla. Breathing 5% carbogen for 7 min resulted in a
      statistically significant increase of 18.3+/-2.6% in HRF parameter 'flow' (p =
      0.024). Increasing IOP to 20 mm Hg did not result in a statistically significant
      change in HRF parameter 'flow' (-9.6+/-7.4%; p = 0.13). Increasing IOP from 20 to
      50 mm Hg, however, resulted in a statistically significant decrease of 40.1+/
      6.6% in HRF parameter 'flow' (p = 0.003). With the applied stimuli, the HRF
      parameter 'flow' changed in the expected direction, i.e. an increase with
      hypercapnia and a decrease with hyperoxia or high IOP. The simplicity of use of
      the HRF instrument suggests that it might be well suited for a non-invasive, at
      least semiquantitative, assessment of changes in blood flow at the papilla.

PMID- 9562086
TI  - The SRKII formula in the calculation of intraocular lens power.
AB  - This study compares the predictive accuracy of the SRKII formula for groups with
      average axial length and long eyes. 344 eyes which underwent cataract extraction
      with implantation of a posterior-chamber intraocular lens were included in the
      survey; 246 eyes had an average axial length (22.0-24.49 mm), and 98 eyes had an
      axial length of more than 24.50 mm. Mean absolute errors were 0.26+/-0.68 dpt in
      the first group and 1.16+/-1.78 dpt in the second group. 94.3% of the average
      eyes were within 1.0 dpt of the expected refraction, 98.8% within 2.0 dpt,
      whereas in the long-eye group 58.2% were within 1.0 dpt and 84.7% within 2.0 dpt.
      The results show that the SRKII formula performed credibly in average-length
      eyes; in the long eyes the ratio of large refractive deviations was greater than
      that of the other group.

PMID- 9562087
TI  - An experimental study of the interleukin 1 levels in aqueous humor after
      intraocular lens implantation.
AB  - This paper studies the interleukin 1 (IL-1) levels in aqueous humor after
      intraocular lens (IOL) implantation in rabbits and discusses the effect of IL-1
      on postoperative anterior ocular inflammation. Twenty-seven pigmented rabbits
      were divided into three groups: in the first group, the IOL were placed in the
      capsular bag after lens extraction; in the second, the lenses of rabbits were
      removed without IOL implantation, and the third served as the control group
      without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days,
      aqueous humor samples were obtained. MTT colorimetry was employed to detect the
      presence of IL-1. The data were closely studied by means of analysis of variance
      with SAS software. The IL-1 level in aqueous humor reached its maximum on the
      14th postoperative day in the IOL-implanted group, and the IL-1 levels in aqueous
      humor were significantly higher (p < 0.05) on the 1st, 3rd, 7th and 14th days
      postoperatively in the IOL-implanted group than in the non-surgical-intervention
      group and extracapsular-lens-extracted group. The result suggests that there is a
      physical relation to the IOL itself, a relation that induces the secretion of IL
      1. The result, however, is also likely to have merely come from the mechanical
      factors related to the presence of the IOL itself.

PMID- 9562088
TI  - Evaluation of serotonin levels in human aqueous humor.
AB  - PURPOSE: Serotonin is biochemically present in the iris and ciliary body of
      animals and humans. Controversial findings are reported about the concentrations
      of serotonin in aqueous humor with respect to plasma in humans. The aim of this
      study was to evaluate the levels of serotonin both in aqueous humor and plasma in
      human subjects. METHODS: In 50 patients with glaucoma or cataract, plasma and
      aqueous humor serotonin levels were measured by HPLC with electrochemical
      detection. Serotonin plasma levels were also measured in 25 healthy subjects as
      controls. RESULTS: In all patients with cataract or glaucoma, the aqueous humor
      serotonin concentration is significantly lower than that in plasma [1.14+/-0.29
      (SEM) vs. 5.33+/-1.03 ng/ml, p<0.01]. Furthermore, in the same patients and in 25
      healthy controls, serotonin plasma levels were similar. CONCLUSION: Our study
      shows that serotonin is present in human aqueous humor and its concentration is 4
      times lower than in plasma.

PMID- 9562089
TI  - Microbiological investigations to validate the preparation of corneal
      transplants.
AB  - The globe and cornea are colonized by microorganisms and cannot be removed as
      sterile products. Antiseptic measures and storage of the cornea in medium
      containing antibiotics lead to an obvious reduction of the microbial flora.
      Unfortunately there is the possibility of secondary microbial contamination
      during the preparation. Large amounts of bacteria or resistant bacteria can ruin
      attempts to reduce the microbial flora. To validate the whole process of
      preparation we investigated the contamination of removed globes, environment,
      materials, instruments and media for each sequence of operation and eliminated
      sources of contamination. Recommendations are given to ensure a virtually sterile
      product at the end of preparation.

PMID- 9562090
TI  - Histopathological study of the effect of phacoemulsification-aspiration on iris
      muscles.
AB  - Phacoemulsification-aspiration (PEA) followed by peripheral iridectomy was
      performed in 10 patients, and the dissected iris fragments were examined by
      electron microscopy. Organic changes such as cytoplasmic vacuolation and lamellar
      formation were observed in both the sphincter and dilator muscles of the pupil.
      No changes in the axons were detected. The same findings were observed when a
      simian eye was examined after PEA. These results indicate that PEA causes injury
      to iris muscles.

PMID- 9562091
TI  - Iris vascular changes in newborns of diabetic mothers.
AB  - Routine ophthalmic examinations of 600 full-term neonates, including 54 born to
      mothers with insulin-dependent diabetes mellitus and 12 whose mothers had
      developed gestational diabetes, revealed significant tortuosity and dilatation of
      the iris vessels in over half of the infants born to diabetic mothers. Ninety
      percent of the newborns in the diabetic group presented hypoplasia of the iris
      stroma and pupil dynamics were altered in 85%. The vessel changes resolved
      spontaneously within 2 weeks after birth. These changes, which have also been
      observed in cocaine-intoxicated newborns, should raise the suspicion of adverse
      vascular effects in the fetus caused by maternal diabetes.

PMID- 9562092
TI  - Cystic fibrosis and lens opacity.
AB  - Cystic fibrosis (CF) is a fairly common lethal genetic disease in whites,
      inherited via an autosomal recessive pattern. Several clinically evident
      anomalies of the eye such as xerophthalmia, papilledema, retinal alterations and
      optic neuropathy have been described. In the present study we investigated lens
      changes in 40 patients affected by CF, to relate the results to the stage of
      digestive insufficiency. Each patient underwent an accurate ocular examination
      including visual acuity, slit-lamp examination, and measurement of lens
      transparency with the Opacity Lens Meter 701. The results were compared with
      those of an age- and sex-matched control group. The comparison between the lens
      opacity values obtained in the CF patients and those measured in the control
      group showed a statistically significant difference; moreover, lens transparency
      was more decreased in patients with severe digestive insufficiency.

PMID- 9562094
TI  - In vitro Staphylococcus epidermidis growth in some viscoelastic substances
      containing sodium hyaluronate.
AB  - The aim of our study was to verify the in vitro growth of Staphylococcus
      epidermidis in various dilutions of some viscoelastic substances containing
      hyaluronic acid (Healon and Healon GV, IAL, Biolon). Serial twofold dilutions of
      each sterile viscoelastic substance, prepared so as to obtain a final
      concentration ranging from 50 to 0.78% of the product in sterile saline solution
      (0.85% NaCl), were taken out with a pipette that delivered 1.0 ml/tube. One
      hundred microliters of the S. epidermidis inocula, used for the evaluation of the
      positive control of the test organism, was dispensed into each tube. After 24 h
      of aerobic incubation at 37 degrees C, 100 microl of sample was taken out from
      each tube and plated into the specific medium for the growth of the test
      organism. After 24 h of incubation at 37 degrees C, these agar plates were
      examined and the colony-forming unit count of the test organism was compared to
      the corresponding total colony count, acting as a positive control, in order to
      determine the quantitative variation of the test organism grown in the presence
      of the viscoelastic compounds. For the lowest dilutions (from 1:2 to 1:8)
      statistically significant bacterial growth was detected in all tested
      viscoelastic substances. For the highest dilutions (1:64 and 1:128) Biolon and
      Healon GV showed a significant inhibition of S. epidermidis growth. A significant
      inhibition was also observed in the highest dilution (1:128) of Healon. In every
      dilution of IAL a statistically significant increase in bacterial growth was
      observed. It remains to be carefully considered whether S. epidermidis,
      accidentally penetrating the eye via the intraocular lens, could find a culture
      medium in a small amount of sodium hyaluronate left in the capsular bag behind
      the optic.

PMID- 9562093
TI  - Choristoma of the optic nerve: neuroimaging characteristics and association with
      spinal cord lipoma.
AB  - A 54-year-old patient presented with amaurosis of the right eye that resulted
      from a dysontogenetic tumor of the right optic nerve. The tumor involved the
      intraorbital, intracanalicular and intracerebral portion of the right optic
      nerve, without involvement of the chiasm. Although the patient had refused
      further diagnostic surgical exploration, we show that it is possible to establish
      the diagnosis of choristoma of the optic nerve by means of modern neuroimaging
      techniques based on computed tomography and magnetic resonance imaging. It
      appears from neuroimaging that choristomata of the optic nerve and spinal cord
      lipomas represent different manifestations of the same type of tumor. The
      neuroimaging characteristics of both kinds of tumors are discussed.

PMID- 9562095
TI  - Compressive lesions of the abducens nerve in the subarachnoid space disclosed by
      thin-slice magnetic resonance imaging.
AB  - We evaluated the usefulness of thin-slice magnetic resonance (MR) imaging as a
      tool for diagnosing compressive lesions of the abducens nerve in the subarachnoid
      space. We performed thin-slice MR imaging of the brain stem in two patients with
      abducens nerve palsy. Thin-slice MR images showed the abducens nerves in the
      subarachnoid space and clearly showed compressive lesions of the nerves by a
      brain tumor in both cases. These findings suggest that thin-slice MR imaging is
      useful for the evaluation of compressive lesions of the abducens nerve in the
      subarachnoid space.

PMID- 9562096
TI  - Primary ethmoidal sinus oncocytic adenocarcinoma presenting as proptosis.

PMID- 9562097
TI  - Ultrasound biomicroscopic findings in a case of cyclodialysis.
AB  - Ultrasound biomicroscopy (UBM) with a high frequency can be used to evaluate the
      structure of the anterior eye segment in vivo. A 24-year-old male was referred to
      us after 1 month of follow-up by a local ophthalmologist, because of decreased
      visual acuity and hypotony after a blunt eye injury. A cyclodialysis cleft in the
      2- to 4-o'clock position and a cavernous pattern all over the choroid were found
      using UBM. The patient underwent surgical treatment to close the cleft. Even
      after the recovery of intraocular pressure (IOP), the peripheral ciliary body
      around 360 degrees was still separated from the sclera when examined by UBM.
      Despite the detached ciliary body, keeping IOP within normal levels is an
      interesting finding. UBM is helpful in the diagnosis and treatment of traumatic
      cyclodialysis.

PMID- 9562098
TI  - Radiographic features of an aneurysmal bone cyst of the orbit.
AB  - Aneurysmal bone cyst is an unusual benign solitary lesion of bone occurring
      rarely in the orbit. In this report, we present computed tomography and magnetic
      resonance images of an orbital aneurysmal bone cyst involving the frontal bone in
      a 16-month-old boy. The aneurysmal bone cyst exhibited bone destruction, new bone
      formation of the orbital roof and fluid-fluid levels in the lesion following
      hemorrhage. These radiographic features may be useful for diagnosing orbital
      aneurysmal bone cysts.

PMID- 9562099
TI  - Orbital tumor in acute myeloid leukemia associated with karyotype
      46,XX,t(8;21)(q22;q22): a case report.
AB  - Orbital tumor formation in acute myeloid leukemia (AML) is rare as an initial
      symptom. Furthermore, orbital granulocytic sarcoma (myeloid sarcoma) in pediatric
      patients is uncommon. We describe a 5-year-old Japanese girl with a left orbital
      mass as an initial symptom of AML, the mass revealed by computed tomography.
      Peripheral blood and bone marrow pictures and a chromosomal analysis disclosing
      46,XX,t(8;21)(q22;q22) showed AML (M2 according to the French-American-British
      classification). She was treated with antileukemic chemotherapy systemically.
      Three weeks after the initiation of chemotherapy, the orbital tumor regressed
      markedly. AML as an initial symptom of the orbital mass should be fully
      considered in a differential diagnosis, even in the absence of typical leukemic
      symptoms, and chromosomal analysis and immunophenotypical analysis may explain
      the pathogenesis of the extramedullary leukemic tumor.

PMID- 9562100
TI  - Bilateral malignant melanoma of the choroid in the United States.
AB  - We examined a 73-year-old woman with bilateral malignant melanoma of the choroid
      associated with multiple nonocular malignancies. Fine-needle aspiration biopsy
      was performed in the left eye to provide a tissue diagnosis. Cytologic
      examination of the lesion in the left eye confirmed the diagnosis of primary
      malignant choroidal melanoma. This case demonstrates that bilateral malignant
      melanoma of the choroid occurs more frequently than expected, and may be
      associated with nonocular malignancies.

PMID- 9562101
TI  - Choroidal coloboma in two members of a family.
AB  - A family with choroidal coloboma is reported. A 43-year-old Japanese woman with
      choroidal coloboma including the optic disk and extending to the inferior half of
      the fundus in both eyes had horizontal nystagmus, microcornea and mild cortical
      cataract in both eyes. Her 40-year-old younger sister had choroidal colobomas in
      both eyes and also a horizontal nystagmus, microcornea in both eyes and a mature
      cataract in the left eye. They had no systemic abnormalities. Their parents and 2
      younger sisters showed neither ocular nor systemic abnormalities. Choroidal
      coloboma with iris coloboma has been reported frequently, but familial choroidal
      coloboma without involvement of the iris and with no systemic abnormalities is
      rare.

PMID- 9562102
TI  - Downward gaze palsy caused by bilateral lesions of the rostral mesencephalon.
AB  - A 55-year-old man with diabetes mellitus developed diplopia and experienced
      difficulty in moving his eyes in the vertical plane, especially downward.
      Horizontal movement of each eye was normal with exotropia. Magnetic resonance
      imaging revealed small and high signals on both sides of the midbrain near the
      interstitial nucleus of Cajal (INC). Based upon the recent experimental evidence,
      we speculate that bilateral lesions involving the INC may have caused downward
      gaze palsy in our patient.

PMID- 9562103
TI  - Homonymous hemianopsia as the initial manifestation of multiple sclerosis.
AB  - A 28-year-old male patient in good health with no previous neurologic or
      ophthalmoscopic abnormalities developed right homonymous hemianopsia. Magnetic
      resonance (MR) imaging demonstrated bilateral high-signal suprageniculate
      lesions. The lesion located in the left parieto-occipital area was compatible
      with the field defect observed. Oligoclonal bands were present in the
      cerebrospinal fluid. Testing of visual-evoked potentials revealed increased
      latencies in both eyes. The patient was given 1 g/day intravenous
      methylprednisolone for 3 days. The visual fields, as determined by automated
      static perimetry, recovered completely in 2 weeks. Follow-up MR imaging at 1
      month showed no change compared to baseline. Seven months after the initial
      attack he suffered right internuclear ophthalmoplegia, which resolved
      spontaneously within 1 week. Based on the clinical and radiologic findings, the
      final diagnosis was made as clinically definite multiple sclerosis (MS). This
      patient represents a rare case of MS presenting first with homonymous
      hemianopsia.

PMID- 9562104
TI  - Acute respiratory infections: the forgotten pandemic. Communique from the
      International Conference on Acute Respiratory Infections, held in Canberra,
      Australia, 7-10 July 1997.
AB  - Acute respiratory infections kill 4 million children every year in developing
      countries, and most of these deaths are caused by pneumonia. This huge loss of
      life goes virtually unnoticed, despite the fact that we have two very effective
      ways of preventing many of the deaths from pneumonia: Haemophilus influenzae type
      b vaccine, and standardised antibiotic treatment regimens. Although H. influenzae
      type b vaccine has virtually eliminated diseases caused by this organism in
      children in developed countries, failure to appreciate the importance of this
      organism and the high cost of the vaccine has meant that it has not been used in
      developing countries; urgent steps need to be taken to ensure that children in
      developing countries receive H. influenzae vaccine. Streptococcus pneumoniae is a
      major cause of fatal pneumonia in developing countries. Controlled trials are
      needed to define the role of unconjugated 23-valent S. pneumoniae vaccine, and
      the new conjugate vaccine must be made available to children in developing
      countries soon after it is licensed. The World Health Organization has developed
      simple and effective guidelines for the treatment of pneumonia which have been
      incorporated into its Integrated Management of Childhood Illness strategy, and
      this programme should be strongly supported. In developed countries, acute
      respiratory infections are the leading cause of morbidity. The cost of these
      infections is enormous, because of lost earnings and the cost of treatment. There
      is an urgent need for systematic evaluation of existing knowledge about acute
      respiratory infections in developed countries, so that this knowledge can be
      applied to prevention and treatment. Approximately 75% of antibiotics are
      prescribed for acute respiratory infections, and many of these prescriptions are
      unnecessary. Unnecessary use of antibiotics is very expensive, and it has
      contributed to the rapid increase in resistance which has already made some
      bacteria resistant to all antibiotics. Rational guidelines for antibiotic
      prescribing need to be developed, and steps taken to see that they are followed.
      There should be greatly increased use of the existing influenza and pneumococcal
      vaccines in high risk groups in developed countries. New vaccines against
      pertussis, S. pneumoniae, non-serotypable H. influenzae, and respiratory
      syncytial virus have been developed and need to be carefully evaluated. Acute
      respiratory infections are responsible for 8.2% of the world's total burden of
      disability and premature death, but they receive only 0.15% of the research and
      development budget for health. More resources should be allocated to research on
      acute respiratory infections. Drug therapy has little effect on the course of
      viral upper respiratory tract infections. Worldwide, US$8 billion is wasted every
      year on drugs used to treat the symptoms of acute respiratory infections.

PMID- 9562105
TI  - The International Tuberculosis Surveillance Research Unit (TSRU): the first 30
      years.

PMID- 9562106
TI  - How drug resistance emerges as a result of poor compliance during short course
      chemotherapy for tuberculosis.
AB  - OBJECTIVE: To explore mechanisms by which drug resistance might arise as a result
      of poor compliance during short course chemotherapy. DESIGN: Four theoretical
      mechanisms are first described. RESULTS: Examples of the way the mechanisms
      probably operate are taken from: 1) a study of once-weekly chemotherapy with
      streptomycin and isoniazid, and 2) the pattern of drug susceptibility in cultures
      from patients who relapsed after the end of treatment. CONCLUSION: Good
      compliance is vitally important. The value of a fourth drug in the initial phase
      of chemotherapy in preventing resistance is questioned. An explanation for mono
      resistance to rifampicin in patients with the acquired immune deficiency syndrome
      (AIDS) is suggested.

PMID- 9562107
TI  - The use of restriction fragment length polymorphism (RFLP) analysis for
      epidemiological studies of tuberculosis in developing countries.
AB  - DNA fingerprinting, of which restriction fragment length polymorphism (RFLP)
      typing is the most common method used, has permitted novel investigations of the
      epidemiology and pathogenesis of tuberculosis. The use of IS6110, an insertion
      sequence which is present in Mycobacterium tuberculosis, is generally considered
      to be the standard RFLP method, but other molecular typing techniques may be used
      as adjuncts in selected circumstances. A number of epidemiologic studies using
      RFLP typing have been done in both industrialized and developing countries. The
      major findings include the confirmation or identification of chains of
      transmission (of both drug-sensitive and drug-resistant strains of tuberculosis),
      distribution of strain clusters within populations, differentiation of relapse
      from exogenous reinfection, better understanding of the pathogenesis of
      tuberculosis, identification of laboratory cross-contamination, and insight into
      the molecular evolution of the species. For developing countries, where the
      burden of tuberculosis is greatest, three major areas of investigation for the
      use of RFLP analysis in epidemiologic studies of tuberculosis have been
      identified: 1) community transmission, 2) nosocomial transmission, and 3) human
      immunodeficiency virus (HIV)-related tuberculosis. Elements of protocols are
      suggested which can be used by investigators to perform well-designed
      epidemiologic studies which will be relevant to developing countries and which
      are likely to have an impact on control programmes in these settings.

PMID- 9562108
TI  - The seventh nationwide tuberculosis prevalence survey in Korea, 1995.
AB  - SETTING: Nationwide random sample survey for tuberculosis prevalence in Korea in
      1995. OBJECTIVE: To investigate the prevalence of tuberculosis infection,
      morbidity and drug resistance, and BCG coverage, and to compare the findings with
      those of the previous six surveys. DESIGN: The following investigations were
      performed: tuberculin test, BCG scar screening, chest miniature radiography (70 x
      70 mm) for those aged over five years, sputum direct smear, culture and drug
      susceptibility test, and a questionnaire to obtain history of antituberculosis
      chemotherapy and symptoms. RESULTS: The coverages of the 1995 survey were as
      follows: tuberculin 87.0%, radiology 88.4%, bacteriology 98.3%. The observed
      tuberculin positivity (> or =10 mm in diameter) of subjects aged under 30 was
      15.5%. The prevalence of pulmonary tuberculosis per 100000 has decreased in the
      last 30 years: direct smear positive from 686 to 93, smear and/or culture
      positive from 940 to 219, active tuberculosis from 5065 to 1032. Rates of drug
      resistance have also fallen: of those with no previous chemotherapy from 26.2% to
      5.8%, of those with history of chemotherapy from 55.2% to 25.0%, and in total
      from 38.0% to 9.9%. BCG scar prevalence of infants (aged under one year) was
      87.7%, and of those under 30 it was 91.8% in 1995. CONCLUSION: Tuberculosis
      prevalences and the drug resistance rates have decreased significantly.

PMID- 9562109
TI  - Pulmonary tuberculosis in the border region of Chiapas, Mexico.
AB  - OBJECTIVES: To estimate the prevalence of pulmonary tuberculosis (PTB) in chronic
      cough patients seeking care at a second level hospital for any complaint, and to
      identify groups more likely to test TB smear-positive, within the Border Region
      of Chiapas, Mexico. METHODS: Active case finding of patients with chronic cough
      (cough of 15 days or more) was carried out among all patients aged over 14 years
      seeking care for whatever reason in the only hospital in the region for patients
      not covered by insurance. The coughers identified (n=221) were interviewed and
      three sputum samples requested for acid-fast smears. In order to identify groups
      at greater risk a logistic regression model was constructed. RESULTS: A rate of
      21 positive PTB smears per hundred patients was found (95% Confidence Interval
      [CI]=15.5-26.6). The main factors associated with positive PTB were age,
      occupation and weight loss. The subgroup of chronic cough patients of those aged
      35-44 years, agricultural workers and those who had lost weight, had the greatest
      likelihood of positive PTB smears (68.7%). CONCLUSION: In hospitals that treat
      rural patients, special efforts should be made to make health personnel more
      aware of the need to investigate respiratory symptoms in all of their patients,
      particularly in the subgroups identified with the greatest likelihood of being
      positive for TB.

PMID- 9562110
TI  - DOTS in Cambodia. Directly observed treatment with short-course chemotherapy.
AB  - SETTING: Since the 1970s, Cambodia, a country of 10 million people in South East
      Asia, has experienced war, genocide and the virtual dismantling of the health
      system. It has a severe tuberculosis (TB) problem, with a new tuberculosis case
      notification rate, all forms, of about 150 per 100000 population and a
      tuberculosis programme, established in the early 1980s, achieving cure rates of
      only 40-50% in the last decade. OBJECTIVE: To describe the implementation of a
      DOTS programme (directly observed treatment with short-course chemotherapy) under
      difficult conditions and its rapid success on a nation-wide scale. DESIGN: The
      World Health Organisation's recommended strategy was implemented in a phased
      manner throughout the country from 1994. The resources for TB drugs and running
      costs came from 13 sources. The DOTS strategy was gradually introduced after
      training and with regular supervision into 120 TB units inside general public
      hospitals at provincial and district level, after a mapping exercise; 75% of
      tuberculosis cases, all forms, are hospitalized during the entire initial phase
      and 85% of the total number of tuberculosis cases received free food from the
      World Food Programme. RESULTS: Two and a half years after the start of the new
      programme, DOTS was implemented in 85% of all public hospitals. In 1996, case
      detection rates had reached 127 smear-positive PTB (pulmonary tuberculosis) and
      149 PTB all forms per 100000 inhabitants; 90% of all tuberculosis patients
      received DOTS. From January 1994 to June 1995, 4164 new cases started category 1
      treatment (2ERHZ/6EH). Of these, 89% were cured or completed treatment, 5%
      defaulted, 3% died, 1% were treatment failures and 2% transferred out.
      CONCLUSION: The DOTS strategy can be successfully implemented in even very
      difficult conditions such as those found in Cambodia.

PMID- 9562112
TI  - Preventability of incident cases of tuberculosis in recently exposed contacts.
AB  - SETTING: Contacts of tuberculosis (TB) cases are at risk for TB. If contact
      screening and intervention are effective, one would expect a reduced incidence of
      TB in contacts who have been screened. OBJECTIVE: To measure the incidence of TB
      in contacts during a 2-year follow up, and to estimate the preventability of
      incident cases. METHODS: A retrospective cohort study of 783 contacts screened in
      Victoria, Australia, in 1991. Contacts were matched with the TB registry for the
      following 2 years. Screening records were reviewed. RESULTS: The rate of TB in
      contacts was 511/100000 population/year for the first 2 years. In Poisson
      regression models the only significant variable predicting disease was skin test
      reaction size. Six of eight incident cases were potentially preventable, with a
      lowest achievable incidence rate of 128/100000/year. CONCLUSION: Contacts who
      underwent screening for TB through a state screening programme had a high
      incidence of TB during the 2 year follow up. Published rates of TB of 425
      670/100000 in untreated contacts suggests that the Victorian screening programme
      had minimal impact on the natural history of disease progression. Intrinsic
      programme factors such as the appropriateness of the guidelines, adherence to
      guidelines and rates of preventive therapy need to be evaluated. The devolution
      of the TB programme in the 1980s also reduced its efficacy. Systematic assessment
      of screening programmes for efficacy and outcome is part of good public health
      practice.

PMID- 9562111
TI  - Should we take a history of prior treatment, and check sputum status at 2-3
      months when treating patients for tuberculosis?
AB  - SETTING: Pinetown, South Africa (1975-1983). OBJECTIVE: To determine the value of
      previous treatment history and sputum smear examination at 2-3 months in
      predicting treatment failure and relapse in tuberculosis patients treated with
      four drugs given twice weekly for six months under direct observation. DESIGN:
      Four cohort studies among 562 ambulant adults with culture positive pulmonary
      tuberculosis, designed to test the effectiveness of isoniazid 600-900 mg,
      rifampicin 600 mg, pyrazinamide 2-3 g, and streptomycin 1-2 g, given twice
      weekly. The same drug regimen was given to all patients irrespective of previous
      treatment history. Therapy was not changed if smears remained positive at 2-3
      months. RESULTS: Positive predictive values of a history of previous treatment
      for a positive smear at 2-3 months (18.3%), treatment failure (5.2%), and relapse
      (9.4%) were poor. Although patients with positive smears at 2-3 months were more
      likely to fail therapy than patients with negative smears (relative risk=4.5, 95%
      Confidence Interval [CI]: 1.6-12.8), positive predictive value for treatment
      failure was only 12.5%. Although relapse was more frequent in patients with
      positive smears than those with negative smears (9.7% vs 6.2%; P=0.4), most
      patients who relapsed had been smear negative at 2-3 months (18/21). CONCLUSION:
      A four-drug rifampicin-containing regimen can safely be given twice weekly under
      direct observation to both new and retreatment cases, and the 2-3 month smear
      examination can safely be omitted.

PMID- 9562113
TI  - Detection of anti-interferon-gamma autoantibodies in subjects infected by
      Mycobacterium tuberculosis.
AB  - SETTING: Among the cytokines involved in defensive mechanisms against
      Mycobacterium tuberculosis infection, special attention has been given to
      interferon-gamma (IFN-gamma); a local synthesis of this cytokine as well as IL-2
      (type 1 cytokines) at the site of disease in patients with tuberculous pleuritis
      has been demonstrated. Moreover, high levels of IgG autoantibodies against IFN
      gamma have been shown in several clinical situations. It has been suggested that
      these antibodies could serve to limit the intensity or duration of the immune
      response or be able to interfere with the pathophysiological effects of IFN
      gamma. OBJECTIVE: To investigate the potential role of anti-IFN-gamma antibodies
      in the course of M. tuberculosis infection. DESIGN: Investigation of the presence
      of these antibodies in sera from healthy and ill subjects infected with M.
      tuberculosis in relation to the extent of the disease and the presence of IFN
      gamma in sera by enzyme-linked-immunosorbent assay (ELISA). In order to
      investigate the presence of these antibodies at the site of infection we included
      12 pleural fluids from tuberculosis patients and 9 pleural fluids from other
      origins. RESULTS: In the course of M. tuberculosis infection the production of
      anti-IFN-gamma IgG antibodies is induced, being particularly higher in healthy
      skin test converters. Among tuberculosis patients, the presence of anti-IFN-gamma
      autoantibodies is significantly associated with detectable levels of the cytokine
      in sera. Levels of anti-IFN-gamma antibodies in moderately advanced and far
      advanced tuberculosis patients are significantly greater than in healthy
      individuals. These antibodies increase at the site of infection. CONCLUSION: Anti
      IFN-gamma antibodies must be considered as a new element in the immune response
      to M. tuberculosis. It would be of great interest to investigate this point
      especially at the site of infection.

PMID- 9562114
TI  - Standardisation of sensitivity tests.

PMID- 9562115
TI  - Intestinal tuberculosis.

PMID- 9562116
TI  - Guidelines for surveillance of drug resistance in tuberculosis. WHO Geneva/IUATLD
      Paris. International Union Against Tuberculosis and Lung Disease.

PMID- 9562117
TI  - Private participation for the public good.

PMID- 9562118
TI  - A review of sex differences in the epidemiology of tuberculosis.
AB  - Globally, the prevalence of infection with Mycobacterium tuberculosis is similar
      in males and females until adolescence, after which it is higher in males. In
      industrialized countries in the middle of this century (1930s to 1950s), females
      aged 15 to 34 years had higher tuberculosis notification rates than males of the
      same age. However, as notification rates in these countries decreased over time,
      rates in males became higher than those of females for all ages over 15. Present
      notification rates of both sexes combined in many developing countries are
      similar to those of industrialized countries in the middle of the century,
      although the sex and age pattern is similar to that in industrialized countries
      at present, with men's disease rates exceeding women's after the age of 15. These
      findings raise the possibility that cases of tuberculosis among women are being
      under-reported in developing regions. This is supported by the results of a study
      comparing active and passive case-finding in which women with tuberculosis were
      under-notified to public health authorities when relying on passive case-finding.
      In addition, epidemiological evidence from the pre-human immunodeficiency virus
      (HIV) era shows that young to early-middle-aged women progress from infection to
      disease with greater frequency than do men. This elevated frequency of
      progression among women now coincides with a peak in HIV prevalence among women
      of the same age. National Tuberculosis Programmes must assess possible sex
      differences that exist in their countries. In addition, information about the
      risks of tuberculosis in younger women should be incorporated into maternal and
      child health, and HIV/AIDS programmes. Further research comparing sex differences
      in tuberculosis rates, preferably using active as well as passive case-finding,
      would be necessary to determine whether young women are undernotified in
      developing countries.

PMID- 9562119
TI  - Tuberculosis control in refugee populations: a challenge to both relief agencies
      and national programs.
AB  - Today's worldwide tuberculosis epidemic and the movement of a growing number of
      refugees overlap geographically and have made tuberculosis control in refugee
      populations an issue of increasing importance. However, in developing countries,
      where both of these problems are concentrated, tuberculosis control in refugee
      populations remains a largely unmet need. Experience shows that despite difficult
      field conditions, tuberculosis control programs can be managed successfully in
      this setting. The range of outcome results reported for treatment completion and
      defaulting is, however, wide. Analyzing possible determinants for observed
      variation in treatment outcome results, this paper outlines prerequisites for
      establishing a tuberculosis control program in a refugee setting. An attempt is
      made to formulate a general strategy for the main policies which, if applied
      consistently, will reduce morbidity, mortality and transmission of tuberculosis
      among refugee populations living in camps. Criteria for the evaluation and
      monitoring of such a program are discussed.

PMID- 9562120
TI  - Childhood tuberculosis: an index measuring the ability to detect cases early.
AB  - SETTING: Tuberculosis control programmes are conventionally monitored using data
      from sputum smear positive adult patients. Good overall results may mask
      significant and avoidable shortcomings with tuberculosis control in children.
      OBJECTIVE: To develop a specific surveillance tool for child patients, using the
      ability to detect cases early as a parameter for the impact of control measures.
      DESIGN: A simple index of early detection was compiled with values ranging from 0
      to 100. Three groups of tuberculous children diagnosed in Germany between 1985
      and 1994 (n = 303), and five other groups from the literature, were used to make
      a preliminary assessment of the validity of the index. RESULTS: The index values
      of 10, 13 and 24 for the German groups correlate well with other analysed patient
      data and the different functions of the institutions where the patients were
      diagnosed. Comparable characteristics could be found when applying the index to
      published data of other cases, with values of between 12 and 74. CONCLUSION: The
      proposed index seems suitable for monitoring early detection of child cases.
      Unexpected trends can be disclosed or effects of changed programme activities
      assessed. Routine use of the index would help the health services focus their
      attention on problem areas and specific patient groups with extremely low or
      falling index values. Conclusions can be drawn regarding the overall impact of
      the control programme.

PMID- 9562121
TI  - Procedures for developing a simple scoring method based on unsophisticated
      criteria for screening children for tuberculosis.
AB  - OBJECTIVE: To develop a scoring system for screening children for tuberculosis
      (TB) and for selecting suspects for further investigation in tuberculosis control
      programmes. Application of the score model, which would not require sophisticated
      or expensive technology, would be directed towards resource-poor countries with
      high prevalences of tuberculosis, where health care workers have to deal with
      diagnostic problems away from district hospitals or diagnostic facilities.
      DESIGN: Based on contributions from members of an IUATLD task group from 10
      countries on the use of diagnostic criteria in childhood tuberculosis, criteria
      were selected to be used as elements in a score model. Data were collected by
      standardised questionnaire on 879 subjects aged under 15 years. Of these, 794
      were considered probable or confirmed cases of tuberculosis by the diagnosing
      doctors. From each record, the criteria/procedures used in the diagnosis of
      probable/confirmed TB and regarded by the doctors as relevant criteria were
      selected. Bacteriology, histology and chest radiography were used either singly
      or collectively as the definitive reference (gold standard) against which the
      more subjective criteria (symptoms, clinical signs, skin test) would be
      evaluated. The latter criteria cited as relevant were then ranked and further
      explored for inclusion in the score model. The relative importance of each
      criterion to every other criterion on the list was expressed as weights,
      determined by employing a logarithmic least squares method to solve the ratio
      scale estimation problem which underlies decision-making involving more than one
      criterion. The resultant values were then assigned to each criterion in the final
      score model. RESULTS: The five clinical criteria thought to be most relevant as
      predictors of disease in children were history of contact with a case of
      tuberculosis, positive skin test, persistent cough, low weight for age, and
      unexplained/prolonged fever. In selecting the optimal cut-off points for the
      model at which tuberculosis would be suspected, low sensitivity and specificity
      (below 70%) but reasonably good positive predictive values (60%-77%) were
      obtained, depending on age group and epidemiological setting. In low tuberculosis
      prevalence settings, heavy reliance is placed by the model on a history of
      contact with a household case of tuberculosis and on a positive skin test, both
      of which have to be true. For high prevalence settings, more or less equal
      weighting is assigned to all five elements. Case contact and skin tests are less
      important, with low body weight, prolonged fever and cough being more indicative
      of tuberculosis. CONCLUSION: The model provides for epidemiological differences
      between target populations and should prove successful as a screening tool to
      select children for further investigation by radiography and bacteriology.

PMID- 9562122
TI  - Few opportunities found for tuberculosis prevention among the urban poor.
AB  - SETTING: Grady Memorial Hospital, a public hospital in Atlanta, Georgia, a city
      with high rates of tuberculosis. OBJECTIVE: To identify specific points of
      contact with the public health system where high risk individuals could receive
      tuberculin testing and isoniazid preventive therapy. DESIGN: Patient interviews
      and medical chart reviews of tuberculosis patients diagnosed in hospital between
      October 1993 and December 1994. RESULTS: In total 151 tuberculosis patients
      participated: 80% were male, 89% African American, the mean age was 40; 50% were
      HIV co-infected. Three fourths reported no regular source of medical care. The
      only potential public health sites at least one third of the patients had
      encountered in the five years prior to tuberculosis diagnosis were correctional
      institutions (44%) and public hospital in-patient wards (37%). Duration of
      incarceration was six months or more in only 13% of patients. Of 108 (71%)
      patients who had identified substance abuse problems, only 25% had been in
      treatment programs. CONCLUSION: We conclude that most tuberculosis cases in this
      community occurred in persons with poor access to health care and few
      opportunities for public health intervention. Tuberculosis prevention for this
      high risk population can best be accomplished by focusing efforts on early case
      identification, completion of therapy and contact investigations.

PMID- 9562123
TI  - Drug resistant tuberculosis in Estonia.
AB  - SETTING: The incidence of drug resistant tuberculosis in Estonia has increased
      rapidly during the last five to six years. OBJECTIVE: To investigate the drug
      resistance patterns of Mycobacterium tuberculosis isolated from tuberculosis
      patients in Estonia. RESULTS: In 1994, 623 cases of tuberculosis were diagnosed
      in Estonia, 518 new cases with no previous history of tuberculosis, and 105 with
      a history of previous treatment for tuberculosis. All pulmonary M. tuberculosis
      isolates from 1994 were analysed for drug susceptibility. Of the 302 new cases
      (58.3%) that were culture verified, 28% had isolates resistant to one or more of
      the four drugs tested (isoniazid, rifampicin, streptomycin, ethambutol), and 9%
      had multi-drug resistant (resistant to at least isoniazid and rifampicin)
      strains. CONCLUSION: The incidence of drug resistance in M. tuberculosis is high
      in Estonia.

PMID- 9562124
TI  - Directly observed therapy in an inner city hospital.
AB  - SETTING: A directly observed therapy (DOT) tuberculosis (TB) program in a large
      urban teaching hospital in the East Harlem section of New York City. OBJECTIVE:
      In response to an emergent epidemic of TB, the State Department of Health
      mobilized a coalition of providers outside the public sector to provide DOT and
      medical care for people with TB, with the goal of treatment until cure. The
      results of the first 150 patients of one program are reviewed. DESIGN: A
      multidisciplinary DOT team coordinated treatment at several sites within and
      without the institution, according to established medical regimens. RESULTS: The
      program served a hard-to-reach population, 63% human immunodeficiency virus (HIV)
      positive, 64% substance users, 17% inadequately housed and 15% indigent. In the
      program's first three years there was 85% overall compliance with DOT visits.
      Using the completion of therapy index, 66% of patients completed therapy, 13%
      remained on treatment, 7% transferred to self medication and 1% were lost to
      follow up. No patient on DOT developed a drug resistant organism. There were no
      hospital readmissions for TB. CONCLUSION: The experience of this program
      demonstrates the efficacy of an intensive, personalized DOT program in ensuring
      treatment until cure.

PMID- 9562125
TI  - Adenosine deaminase activity and lysozyme levels in bronchoalveolar lavage fluid
      in patients with pulmonary tuberculosis.
AB  - SETTING: The estimations of adenosine deaminase (ADA) activity and lysozyme (LYS)
      levels in pleural fluid have been proved useful tools in the diagnosis of
      tuberculous pleural effusions. Little is known about their usefulness when
      estimated in bronchoalveolar lavage fluid (BALF). OBJECTIVE: To evaluate whether
      both ADA activity and LYS levels in BALF could be employed in the diagnosis of
      pulmonary tuberculosis, and especially in active but acid fast bacilli (AFB)
      smear negative cases. DESIGN: ADA activity and LYS levels were determined in BALF
      and serum obtained on the same day in 28 patients with tuberculosis, 21 with
      interstitial lung diseases, 14 with lung cancer and 13 with infectious diseases.
      RESULTS: Patients with pulmonary tuberculosis had significantly higher ADA
      activity in BALF than patients with non-tuberculous lung diseases (P < 0.001).
      High BALF ADA activity in pulmonary tuberculosis patients suggests increased
      local production. In contrast, in this group of patients BALF LYS levels were not
      significantly higher than in the other groups of patients, but were in the group
      with interstitial lung diseases. CONCLUSION: BALF ADA activity seems to be a
      useful tool in the differentiation of tuberculosis from other lung diseases. Its
      estimation can be restricted to the detection of cases with AFB negative smears.

PMID- 9562126
TI  - The genetic diversity of Mycobacterium tuberculosis strains in Thailand studied
      by amplification of DNA segments containing direct repetitive sequences.
AB  - OBJECTIVE: To develop and use a polymerase chain reaction (PCR) method for
      studying the genetic diversity of Mycobacterium tuberculosis. DESIGN: Two
      polymorphic DNA segments of M. tuberculosis H37Rv were identified and sequenced.
      Primers were then designed for simultaneous amplification of both polymorphic
      segments. The method was used for studying 179 clinical isolates of M.
      tuberculosis that had been previously characterized by Southern hybridization
      with IS6110. RESULTS: Both polymorphic segments contained direct repetitive
      sequences. In one segment the direct repetitive sequences were within the
      putative coding sequence of alpha-isopropylmalate synthase gene. After amplifying
      both segments of the 179 isolates, 40 patterns of PCR products could be
      identified. The method was able to differentiate 38 IS6110-single-banded isolates
      into 23 types. Most of the isolates belonging to the Beijing family had PCR
      products identical to the H37Rv strain. The PCR products of the members of the
      Nonthaburi group were similar to each other. CONCLUSION: These results agree with
      the hypothesis that the members of the Beijing family and the Nonthaburi group
      descended from two common ancestors. The PCR method might be useful for
      differentiating strains of M. tuberculosis that contain a single copy of IS6110.

PMID- 9562127
TI  - Detection of anti-lipoarabinomannan antibodies for the diagnosis of active
      tuberculosis.
AB  - SETTING: A serological test that contributes in diagnosing tuberculosis would aid
      patient management. OBJECTIVE: To evaluate MycoDot, a new commercially available
      serological test, for the detection of immunoglobulin G antibodies to
      lipoarabinomannan (LAM), a glycolipid common to mycobacteria. DESIGN: Serum
      samples from 102 non-human immunodeficiency virus (HIV)-infected patients with no
      previous history of tuberculosis and with suspected active pulmonary (66) and/or
      extra-pulmonary (36) tuberculosis were investigated; 50 HIV-negative healthy
      subjects, sputum culture-negative, tuberculin skin test negative and with no
      history of tuberculosis, were used as controls. RESULTS AND CONCLUSION: In 28
      patients with microbiologically ascertained tuberculosis 25/28 serum samples were
      positive, whereas the test was negative in two patients with renal tuberculosis
      and in one with pulmonary tuberculosis. The remaining 74 serum samples were
      negative. The follow-up of these patients excluded a mycobacterial infection.
      Control subjects were negative. On the basis of our design, the MycoDot test,
      with its rapidity and degree of sensitivity, is suitable for routine use in
      laboratory diagnosis of both pulmonary and extrapulmonary tuberculosis.

PMID- 9562128
TI  - Computed tomography findings of tuberculous pleurisy.
AB  - SETTING: Review of the records of 491 patients with tuberculous pleurisy
      hospitalized between 1993 and 1995 in Izmir, Turkey. Those cases with typical
      histopathology or demonstrated acid-fast bacilli on pleural needle biopsies
      and/or positive pleural fluid/tissue cultures and available computed tomography
      (CT) scans are included. OBJECTIVE: To determine the CT features of tuberculosis
      of the pleural space. DESIGN: The CT scans of 66 patients with proven tuberculous
      pleurisy were interpreted retrospectively by three observers. RESULTS: Of 66
      patients, 65 (98.5%) had pleural effusions; 38 (57.5%) had pleural lesions; six
      (9%) had involvement of interlobar fissure; and one patient (1.5%) had
      involvement only of the mediastinal pleura. All but one of the pleural lesions
      involved regular thickening of greater than 1 cm. Fibrotic parenchymal changes
      were seen in 11 of 66 patients (17%), cavitary changes were seen in eight (12%),
      and heterogeneous nodular shadows were seen in four (6%). Two cases (3%) had
      parenchymal consolidation and one (1.5%) had a calcified subpleural nodule. In
      39% (26/66) of cases, hilar and mediastinal lymphadenopathy was identified.
      CONCLUSION: Tuberculous pleurisy in our series was characterized on CT by the
      presence of pleural effusion, often with smooth pleural thickening; rarely was
      there involvement of the mediastinal pleura. Underlying lung parenchymal
      abnormalities were seen in 39% of cases. Although these findings are non
      specific, they may help to distinguish tuberculous pleurisy from other causes of
      pleural effusion, such as malignancy.

PMID- 9562129
TI  - The effect of dosage cards on compliance with directly observed tuberculosis
      therapy in hospital.
AB  - We evaluated the effect of a dosage card signed by both patient and health worker
      on compliance in a tuberculosis ward. Compliance was assessed by testing a urine
      specimen from each patient for the presence of isoniazid and rifampicin pre
      intervention and at two weeks, six weeks and 16 months post-intervention. Pre
      intervention compliance was 62% and increased to 88%, 91% and 93% in the short,
      medium and long-term, respectively (P = 0.03, P = 0.02, P < 0.01). The assumption
      that directly observed therapy is successfully practised in hospital is not
      always correct. Simple inexpensive measures can improve compliance and have an
      impact on tuberculosis control.

PMID- 9562130
TI  - HIV infection among patients with tuberculosis in KwaZulu/Natal, South Africa.

PMID- 9562131
TI  - Adrenocortical function in active pulmonary tuberculosis.

PMID- 9562132
TI  - Treatment regimens in HIV-infected tuberculosis patients. An official statement
      of the International Union Against Tuberculosis and Lung Disease. Paris, 16
      September 1997.

PMID- 9562133
TI  - Gabapentin absorption: effect of mixing with foods of varying macronutrient
      composition.
AB  - OBJECTIVE: To compare the oral absorption profile of gabapentin following
      administration of the contents of opened capsules that were mixed with food
      vehicles of varied macronutrient (protein) composition. DESIGN: An unblinded,
      randomized, single-dose, four-way crossover pharmacokinetic study in nine healthy
      adult men and women volunteers. METHODS: Following an overnight fast, a single
      600-mg dose of gabapentin (2 x 300-mg Neurontin capsules) was given either as an
      intact capsule swallowed with 120 mL of tap water (control, phase I), or after
      capsule contents were opened and mixed with; 4 oz. of applesauce (phase II), 120
      mL of orange juice (phase III), or 4 oz. of fat-free chocolate pudding (phase
      IV). Subjects fasted for 4 hours following drug ingestion. Serial venous blood
      samples were obtained over 24 hours to determine gabapentin serum concentrations.
      Pharmacokinetic variables including AUC, maximum serum concentration (Cmax), and
      time to maximum serum concentration (tmax) were calculated by using standard
      noncompartmental methods. Subjects served as their own controls, and were
      randomly crossed over following a minimum 7-day washout period. Statistical
      analysis was performed by using ANOVA and Student's t-test where appropriate.
      RESULTS: No statistically significant differences in any kinetic variable were
      found between any study arm. A trend was noted for a modest increase in both Cmax
      and AUC in phase IV (chocolate pudding) compared with control (+18.6% and +13.2%,
      respectively). In a comparison of protein (phase IV) versus nonprotein phases
      (phases I-III), gabapentin AUC was 26% greater (47.28+/-14.65 vs. 37.43+/-9.78
      microg/mL x h; p = 0.03), and Cmax was 32% higher (4.72+/-1.04 vs. 3.56+/-0.92
      microg/mL; p = 0.003). CONCLUSIONS: Opening and mixing the contents of gabapentin
      capsules does not significantly impair drug absorption. This may be a viable
      administration option for patients who are unable to swallow intact capsules.
      Dietary macronutrient composition (i.e., protein) may favorably influence
      gabapentin oral absorption.

PMID- 9562134
TI  - Community pharmacists' assessments and recommendations for treatment in four case
      scenarios.
AB  - OBJECTIVE: To evaluate community pharmacists' interpersonal skills, ability to
      make appropriate assessment of a patient' s drug-related problems, and ability to
      propose an appropriate therapeutic plan. DESIGN: A disguised shopper design was
      used. Four different case scenarios were designed, with input from a five-member
      community/primary care pharmacist advisory committee. Two different cases were
      assigned to each of two shoppers. One hundred and one pharmacies were shopped
      twice, totaling 202 shopping experiences. A three-member evaluation committee
      made up of clinical faculty members in ambulatory care and internal medicine
      assessed the appropriateness of the recommendations. SETTING: The study was
      conducted in 101 randomly selected community pharmacies in the Pittsburgh area,
      including both chain and independent pharmacies. MAIN OUTCOME MEASURES: Main
      outcome measures included the quality of the pharmacists' interpersonal skills,
      patient assessment skills, and recommendations. RESULTS: The majority of
      pharmacists demonstrated acceptable to good interpersonal skills. Overall, 31.7%
      of the recommendations were appropriate, while 39.1% were poor (i.e.,
      recommendations that would likely worsen the patient's condition or potentially
      harm the patient). In 33.2% of the cases, recommendations were made without prior
      assessment of the patient's problems. CONCLUSIONS: A lack of clinical knowledge
      and skills should be considered as a barrier that must be overcome if the
      provision of pharmaceutical care is to become a reality in community practice.

PMID- 9562135
TI  - Validation of the Hartford nomogram in trauma surgery patients.
AB  - OBJECTIVE: To validate the Hartford nomogram for once-daily aminoglycoside dosing
      in trauma surgery patients. METHODS: A chart review was performed in trauma
      surgery patients who were started on once-daily aminoglycoside therapy. A peak
      aminoglycoside concentration was drawn 30 minutes after the end of the first or
      second infusion, and a random concentration was drawn approximately 10 hours
      after the dose. The 10-hour random concentration was used to validate the
      Hartford nomogram by predicting the actual dosing interval (determined by
      extrapolating the peak and random concentrations to achieve a trough
      concentration <1 mg/L). The percentage of intervals accurately predicted by the
      nomogram was determined. RESULTS: Forty-nine patients (34 men and 15 women), age
      43.0+/-15.9 y, total body weight 81.3+/-24.5 kg, ideal body weight 68.1+/-10.7
      kg, dosing body weight (DBW) 72.0+/-14.4 kg, and estimated creatinine clearance
      [Cl(cr)] 89.5+/-20.6 mL/min/1.73 m2 were evaluated. Patients received 505+/-105
      mg (7.0+/-0.4 mg/kg) of either gentamicin or tobramycin per dose. The
      concentration 30 minutes after the infusion was 22.4+/-5.9 mg/L, the
      concentration at the end of the dosing interval was 0.20+/-0.46 mg/L, the 10-hour
      random concentration was 2.6+/-1.8 mg/L, the elimination rate constant was 0.26+/
      0.08 h(-1), the elimination half-life was 3.0+/-1.2 hours, and the volume of
      distribution was 19.9+/-7.9 L (0.28+/-0.09 L/kg of DBW). Ninety-eight percent
      (48/49) of the intervals were accurately predicted by the nomogram. CONCLUSIONS:
      In trauma surgery patients with Cl(cr) of more than 60 mL/min/1.73 m2, the
      Hartford nomogram using a single random aminoglycoside concentration accurately
      predicted the same once-daily aminoglycoside intervals as determined by two
      concentrations. Less aggressive therapeutic drug monitoring in this patient
      subpopulation can lead to significant cost savings.

PMID- 9562136
TI  - Pemoline therapy resulting in liver transplantation.
AB  - OBJECTIVE: To describe a case of pemoline-induced liver failure resulting in
      liver transplantation. CASE SUMMARY: A 9-year-old white boy, diagnosed with
      attention deficit/hyperactivity disorder (ADHD) and treated with pemoline,
      developed signs and symptoms of liver failure. Pemoline therapy was discontinued,
      but the patient's liver function continued to decline. Ultimately, a liver
      transplantation was required. DISCUSSION: Pemoline, an agent used in ADHD
      treatment, has been associated with hepatotoxicity with the majority of cases
      occurring in pediatric patients. To our knowledge, this is the second reported
      case of pemoline-induced liver failure resulting in liver transplantation. The
      mechanism of action remains unclear, with several hypotheses being postulated
      including hypersensitivity reactions, dose-related phenomena, and autoimmune
      mediated reactions. CONCLUSIONS: With increasing evidence linking pemoline to
      liver failure, this agent should not be considered first-line therapy for ADHD.
      Prior to initiating therapy, baseline liver function tests should be obtained and
      closely monitored, and parents and patients should be educated on the signs and
      symptoms of liver toxicity.

PMID- 9562137
TI  - Azathioprine hypersensitivity reaction in a patient with ulcerative colitis.
AB  - OBJECTIVE: To describe a case of azathioprine hypersensitivity in a patient with
      ulcerative colitis. CASE SUMMARY: A 40-year-old white man with ulcerative
      colitis, treated with chronic mesalamine and occasional steroids, was admitted to
      the hospital with a 3-day history of fever, nausea, vomiting, and a rash.
      Fourteen days prior to admission, the patient had been started on azathioprine
      for ulcerative colitis. Upon admission, azathioprine therapy was temporarily
      withheld, resulting in resolution of his signs and symptoms. Symptoms returned
      when azathioprine was restarted. It was decided that these signs and symptoms
      were most likely caused by azathioprine hypersensitivity, and the agent was
      discontinued. DISCUSSION: To our knowledge, this is the first reported case of
      azathioprine hypersensitivity in a patient with ulcerative colitis. The time
      course and presenting signs and symptoms support the diagnosis of azathioprine
      hypersensitivity, as does the patient's response to rechallenge. The mechanism of
      this hypersensitivity reaction is unclear, but may involve the nitroimidazole
      portion of the azathioprine molecule. CONCLUSIONS: Azathioprine hypersensitivity
      often presents with signs and symptoms resembling a systemic infection such as
      fever, leukocytosis, and evidence of end organ dysfunction. The diagnosis of
      azathioprine hypersensitivity should be considered in patients who have recently
      either initiated or increased their dosage of azathioprine.

PMID- 9562138
TI  - Chromium picolinate toxicity.
AB  - OBJECTIVE: To describe a case of toxicity secondary to chronic ingestion of 6-12
      times the recommended daily allowance of over-the-counter (OTC) chromium
      picolinate. CASE SUMMARY: A 33-year-old white woman presented with weight loss,
      anemia, thrombocytopenia, hemolysis, liver dysfunction (aminotransferase enzymes
      15-20 times normal, total bilirubin 3 times normal), and renal failure (serum
      creatinine 5.3 mg/dL; blood urea nitrogen 152 mg/dL). She had ingested chromium
      picolinate 1200-2400 microg/d for the previous 4-5 months to enhance weight loss.
      The patient had chromium plasma concentrations 2-3 times normal. Thrombotic
      thrombocytopenic purpura and hemolytic uremic syndrome were ruled out by clinical
      findings, peripheral blood smears, and a bone marrow biopsy. The patient was
      managed with supportive measures and received blood product transfusions and
      hemodialysis. Hemolysis stabilized and liver function improved over 6 days. Liver
      function returned to normal prior to discharge. Renal function began to return on
      day 12 and her serum creatinine on discharge was 1.3 mg/dL. One year later, all
      laboratory values were within normal limits. DISCUSSION: Trivalent chromium is an
      essential trace element that is considered safe when ingested in normal
      quantities. Trivalent chromium compounds are used by patients to enhance weight
      loss, increase lean body mass, and/or improve glycemic control. Information
      regarding the toxicity of chromium picolinate is limited. CONCLUSIONS: Chromium
      supplements may cause serious renal impairment when ingested in excess.
      Medication histories should include attention to the use of OTC nutritional
      supplements often regarded as harmless by the public and lay media.

PMID- 9562139
TI  - Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in
      polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms.
AB  - OBJECTIVE: To document a case of serotonin syndrome associated with venlafaxine
      and fluoxetine that did not involve a monoamine oxidase inhibitor, and to examine
      the multiple factors, including pharmacodynamic and pharmacokinetic interactions,
      that likely caused this adverse drug reaction (ADR). CASE SUMMARY: A 39-year-old
      white woman with depression and panic attacks was being treated with fluoxetine,
      trazodone, clonazepam, and cimetidine. After fluoxetine and clonazepam were
      abruptly discontinued, venlafaxine and lorazepam were started. Within 24 hours,
      she developed diaphoresis, tremors, slurred speech, myoclonus, restlessness,
      impaired thinking, and diarrhea. This constellation meets Sternbach's criteria
      for serotonin syndrome. DISCUSSION: The possible contributors to this ADR are
      discussed, including a single drug effect (e.g., an idiosyncratic reaction to
      venlafaxine), a pharmacokinetic interaction, a pharmacodynamic interaction, a
      combined pharmacokinetic-pharmacodynamic interaction, and the patient' s panic
      disorder. CONCLUSIONS: As more serotonergic drugs are developed and used for
      psychiatric disorders, frequently in combination or close temporal proximity,
      clinicians must be aware of and consider the factors that may increase the risk
      of patients experiencing serotonin syndrome.

PMID- 9562140
TI  - Recombinant human growth hormone for AIDS-associated wasting.
AB  - OBJECTIVE: To review the current literature regarding the role of recombinant
      human growth hormone (rhGH) in the treatment of AIDS-associated wasting and to
      briefly describe alternative therapies. DATA SOURCES: A literature search was
      performed on MEDLINE and AIDSLINE for the period from January 1985 through
      September 1997. Key words used in the search strategy were growth hormone, human
      immunodeficiency virus, acquired immune deficiency syndrome, wasting, and weight
      gain. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for
      possible inclusion in this review. Abstracts were included only when they were
      judged to add critical information. Thereafter, the inclusion was restricted to
      English-language articles and abstracts on clinical trials and human studies in
      AIDS-associated wasting. DATA SYNTHESIS: Body wasting, characterized by an
      involuntary loss of body cell mass, is a well-recognized feature of many chronic
      diseases, including infection with HIV AIDS-associated wasting is a metabolic
      disorder characterized by weight loss, depletion of lean body mass (LBM), and
      preservation of body fat, leading to muscle weakness and organ failure. rhGH has
      been approved by the Food and Drug Administration for use in treating AIDS
      associated wasting. The adverse event profile is similar to that of other rhGH
      products. The recommended dosage of rhGH is 4-6 mg administered by subcutaneous
      injection daily. It offers a more expensive alternative to appetite stimulants
      such as megestrol acetate and dronabinol. CONCLUSIONS: Trials with rhGH on the
      control of wasting in patients with AIDS have been encouraging, but with limited
      conclusive evidence of sustainable positive outcomes. Studies demonstrate that
      rhGH increases LBM and decrease adipose tissue, but how these translate into long
      term outcomes such as decreased hospitalization, morbidity, and mortality has yet
      to be determined. A formal health economic assessment is needed to properly
      determine the impact of rhGH on the healthcare system.

PMID- 9562141
TI  - HIV wasting syndrome: treatment update.
AB  - OBJECTIVE: To review the pathophysiology and treatment of HIV wasting syndrome.
      DATA SOURCES AND STUDY SELECTION: MEDLINE searches (January 1987-September 1997)
      of the English-language medical literature were conducted. Bibliographies were
      also selected during a manual review. DATA SYNTHESIS: HIV-related weight loss,
      often referred to as HIV wasting syndrome, is a common manifestation of advanced
      HIV infection. Wasting in HIV involves the preferential loss of lean body mass
      with a paradoxical preservation of body fat. The etiology of wasting appears to
      be the result of many factors, which may include decreased caloric intake,
      malabsorption, alterations in energy expenditure and metabolism, cytokine
      effects, and endocrine dysfunction. Pharmacologic treatment options include
      appetite stimulants (e.g., dronabinol, megestrol acetate), cytokine inhibitors
      (e.g., thalidomide, cyproheptadine, ketotifen, pentoxifylline, fish oil, N
      acetylcysteine), and anabolic agents (e.g., testosterone, nandrolone,
      oxandrolone, recombinant human growth hormone). CONCLUSIONS: Wasting associated
      with HIV has a high morbidity and mortality rate if not adequately managed.
      Therapeutic strategies include appetite stimulants, cytokine inhibitors, and
      growth-promoting agents. Selection of the appropriate agent(s) depends on the
      underlying cause for weight loss, adverse effects, and cost of therapy.

PMID- 9562142
TI  - Endothelial dysfunction: implications for therapy of cardiovascular diseases.
AB  - OBJECTIVE: To review current literature regarding endothelial dysfunction in
      cardiovascular diseases and examine implications of these findings for the
      treatment of various cardiovascular disorders. DATA SOURCE: A MEDLINE search of
      basic science articles pertinent to understanding the role of the endothelium in
      the atherosclerotic process and of clinical trials examining the presence and
      treatment of impaired endothelium-dependent vascular relaxation was conducted.
      STUDY SELECTION: Selected basic science articles and reviews were included to
      explain the foundation for subsequent clinical trials. All clinical trials
      examining the treatment of impaired endothelium-dependent vascular relaxation
      were reviewed. DATA SYNTHESIS: Endothelial dysfunction characterized by impaired
      endothelium-dependent vascular relaxation is an early physiologic event in
      atherogenesis. Endothelial dysfunction in peripheral vasculature serves as a
      marker for impairment in coronary arteries. Techniques for measuring endothelium
      dependent vascular relaxation are specific and have a high positive predictive
      value for coronary artery disease, but low sensitivity. Various pharmacologic
      agents have been used in an attempt to improve endothelial function, but only
      lipid-lowering agents and estrogen supplementation have been shown to improve
      endothelium-dependent vascular relaxation consistently. Treatments used in
      patients with heart failure or hypertension fail to demonstrate consistent
      improvement. CONCLUSIONS: Endothelial dysfunction serves as a marker for
      cardiovascular disease, but pharmacologic treatment does not consistently restore
      normal endothelial function. Nevertheless, some of these agents are known to have
      positive clinical outcomes. Future research using these techniques will provide
      greater insight into the effects of many commonly used therapies for
      cardiovascular disease on the pathobiology of endothelial dysfunction.

PMID- 9562143
TI  - Rho Chi Lecture. An essential societal role.

PMID- 9562144
TI  - Is amphotericin B test dosing needed?

PMID- 9562145
TI  - The use of omeprazole in the pediatric population.

PMID- 9562146
TI  - Ampicillin-induced neurotoxicity in very-low-birth-weight neonates.

PMID- 9562147
TI  - Prescription and nonprescription analgesic use in Sweden.
AB  - OBJECTIVE: To analyze patterns of prescription and nonprescription analgesic use
      in the general Swedish population, in association with predisposing factors,
      enabling factors, need, and health behavior. DESIGN: Cross-sectional interview
      survey. SETTING: The Swedish Surveys of Living Conditions for the 2-year period
      1988-1989. PARTICIPANTS: A probability sample of all inhabitants of Sweden aged
      18-84 years (n = 11996). MAIN OUTCOME MEASURES: Prescription and nonprescription
      analgesic use during a 2-week period. RESULTS: Women reported use of analgesics
      both with and without prescriptions to a greater extent than did men. Among
      women, 12.2% reported prescription analgesic use and 30.4% reported
      nonprescription analgesic use. The corresponding proportions among men were 7.2%
      and 20.0%, respectively. In the descriptive analyses, prescription analgesic use
      was most common among persons aged 45 years and older, while use of
      nonprescription analgesics was most common in people aged 18-44 years. The
      polychotomous logistic regression analyses showed that headache and
      musculoskeletal pain were strongly associated with prescription analgesic use to
      a similar extent among men and women. Headache was associated with
      nonprescription analgesic use among men and women, but a gender difference was
      found in the association between musculoskeletal pain and nonprescription
      analgesic use. Women with musculoskeletal pain used nonprescription analgesics to
      a greater extent than did men with musculoskeletal pain. Poor health--measured as
      self-perceived health status and physical function--and high use of health care
      were related only to prescription analgesic use. Smoking and being overweight
      were associated with prescription analgesic use among men and with
      nonprescription analgesic use among women; alcohol consumption was associated
      with both types of analgesic use only among women. CONCLUSIONS: This study shows
      that men and women differ in their choice between prescription and
      nonprescription analgesics and that the choice between prescription and
      nonprescription analgesics is influenced by an individual's pain, self-perceived
      health, and lifestyle.

PMID- 9562148
TI  - Should vaccines require a prescription?
AB  - OBJECTIVE: To review the rationale for requiring prescriptions to control vaccine
      access, in contrast to other medications. DATA SOURCES: Literature on
      immunization delivery and health-service barriers was reviewed via MEDLINE search
      and relevant textbooks. Additional literature was obtained from reference lists
      of pertinent articles. DATA SYNTHESIS: Society controls access to medications to
      protect consumers. Many medications have changed from prescription-only to over
      the-counter (OTC) status. No parenteral drug has been switched, although insulin
      has long had OTC status. Limiting access to vaccines has advantages in record
      keeping, storage, injection quality, and response to anaphylactic reactions.
      These advantages are outweighed by 600000 people who will die over the next
      decade for lack of pneumococcal and influenza immunizations. Physicians see most
      of those who die of these diseases, but many neglect to vaccinate them. Three
      options are offered to expand access to these vaccines. The most feasible one
      involves expanding prescribing authority for pneumococcal and influenza vaccines
      to all licensed healthcare professionals and paraprofessionals with physiologic
      and pharmacologic expertise to responsibly vaccinate. Community pharmacies offer
      advantages as immunization delivery sites, in terms of proximity, hours of
      operation, and knowledge of people at highest risk. Expanded professional
      training can ensure high levels of public safeguards while expanding immunization
      delivery. CONCLUSIONS: Society decides the controls needed to protect the health
      of the people. If society restricts vaccine access too severely, people die
      needlessly. Increasing prescribing authority for pneumococcal and influenza
      vaccines to more health professionals will save many lives.

PMID- 9562149
TI  - Systemic adverse effects associated with topically applied latanoprost.

PMID- 9562150
TI  - Multiple congenital malformations associated with topical tretinoin.

PMID- 9562151
TI  - New adverse effect of oxybutynin: "night terror".

PMID- 9562152
TI  - Rugby football and anterior cruciate ligament injury.

PMID- 9562153
TI  - Diagnostic ultrasound in sports medicine.

PMID- 9562154
TI  - Technological advances in scuba diving do not always increase safety.

PMID- 9562155
TI  - Performing arts medicine.

PMID- 9562156
TI  - Exercise and hypertension: facts and uncertainties.

PMID- 9562158
TI  - Application of a standard test to the in vitro performance of mouthguards.
AB  - OBJECTIVE: To use a simulated upper jaw made from a rubber arch containing
      replaceable ceramic teeth and a renewable composite ceramic jawbone to compare
      the effectiveness of seven custom made mouthguard designs and a "boil and bite"
      mouthguard. METHODS: Following an earlier development of a standard impact test
      using a selection of projectile shapes and energies, the most sensitive
      conditions were selected. These were then applied to a series of six guards
      constructed in ethylene vinyl acetate and styrene butadiene. The guards were
      constructed to reflect possible variations in both design and materials. RESULTS:
      Significant differences between the mouthguard performances were observed in
      response to the impact conditions selected. All the custom made designs gave
      better performance than the "boil and bite" mouthguard. CONCLUSIONS: The
      differences observed indicated that the standard test should be sensitive enough
      to be used as an assessment procedure for the approval of the manufacture of
      these safety devices. A sequence of tests on eight identical mouthguards selected
      from a batch of 12, based on the best design, gave remarkably consistent results,
      indicating that both the manufacturing technique and the test method are
      reliable. The features of the best design should be incorporated into the current
      "best practice" for the construction of these devices.

PMID- 9562157
TI  - A systematic review of physical activity promotion in primary care office
      settings.
AB  - OBJECTIVE: To assess the efficacy of physical activity promotion in primary care
      office settings. DESIGN: Systematic review of clinical trials in which the
      efficacy of physical activity promotion was investigated in a primary care office
      setting with at least one month of follow up. SUBJECTS: A total of 13,981 adults,
      aged 17-85+, were included from 203 practices in eight trials assessing physical
      activity promotion in primary care office settings. MAIN OUTCOME MEASURES: Odds
      ratios and 95% confidence intervals were calculated comparing the number of
      participants who increased their physical activity or were active at follow up in
      the intervention group with a control group for each study. RESULTS: Five of
      eight trials where positive with statistically significant results (range 0.91
      6.56), but significant biases or limited clinical relevance of the outcomes were
      found in all trials. Short term trials of less than one year (four of four were
      positive), single-risk-factor trials (three of three were positive), randomised
      clinical trials (two of three were positive), and those assessing moderate levels
      of physical activity (three of four were positive) were most likely to find
      benefit. Only one of four trials lasting longer than a year were positive.
      CONCLUSION: There is limited evidence from well designed trials that office based
      physical activity promotion in primary care settings is efficacious in promoting
      changes in physical activity that could conceivably have lasting clinical
      benefits.

PMID- 9562159
TI  - Perception of pain after resistance exercise.
AB  - OBJECTIVES: The main objective was to assess the influence of resistance exercise
      on pain threshold and pain ratings. Secondary objectives included measuring state
      anxiety, body awareness, systolic blood pressure, diastolic blood pressure, and
      heart rate responses. METHODS: Pressure (3 kg force) was applied to the middle
      digit of the left hand for two minutes using a Forgione-Barber pain stimulator
      before and after (five minute and 15 minutes) resistance exercise and quiet rest.
      Resistance exercise consisted of 45 minutes of lifting three sets of 10
      repetitions at 75% of an individual's one repetition maximum. Quiet rest
      consisted of sitting quietly in a room free from distractions. RESULTS: Data were
      analysed by repeated measures analysis of variance for multifactor experiments.
      Pain threshold was significantly higher (p<0.05) and pain ratings were
      significantly lower (p<0.05) five minutes after resistance exercise. Changes in
      pain perception were accompanied by changes in heart rate, systolic blood
      pressure, and body awareness after exercise. CONCLUSION: A single bout of
      resistance exercise is capable of modifying the sensation of experimentally
      induced pain.

PMID- 9562160
TI  - Contrasting plasma free amino acid patterns in elite athletes: association with
      fatigue and infection.
AB  - AIM: There is little information on the plasma free amino acid patterns of elite
      athletes against which fatigue and nutrition can be considered. Therefore the aim
      was to include analysis of this pattern in the medical screening of elite
      athletes during both especially intense and light training periods. METHODS:
      Plasma amino acid analysis was undertaken in three situations. (1) A medical
      screening service was offered to elite athletes during an intense training period
      before the 1992 Olympics. Screening included a blood haematological/biochemical
      profile and a microbial screen in athletes who presented with infection. The
      athletes were divided into three groups who differed in training fatigue and were
      considered separately. Group A (21 track and field athletes) had no lasting
      fatigue; group B (12 judo competitors) reported heavy fatigue at night but
      recovered overnight to continue training; group C (18 track and field athletes,
      one rower) had chronic fatigue and had been unable to train normally for at least
      several weeks. (2) Athletes from each group were further screened during a post
      Olympic light training period. (3) Athletes who still had low amino acid levels
      during the light training period were reanalysed after three weeks of additional
      protein intake. RESULTS: (1) The pre-Olympics amino acid patterns were as
      follows. Group A had a normal amino acid pattern (glutamine 554 (25.2)
      micromol/l, histidine 79 (6.1) micromol/l, total amino acids 2839 (92.1)
      micromol/l); all results are means (SEM). By comparison, both groups B and C had
      decreased plasma glutamine (average 33%; p<0.001) with, especially in group B,
      decreased histidine, glucogenic, ketogenic, and branched chain amino acids
      (p<0.05 to p<0.001). None in group A, one in group B, but ten athletes in group C
      presented with infection: all 11 athletes had plasma glutamine levels of less
      than 450 micromol/l. No intergroup differences in haematological or other blood
      biochemical parameters, apart from a lower plasma creatine kinase activity in
      group C than in group B (p<0.05) and a low neutrophil to lymphocyte ratio in the
      athletes with viral infections (1.2 (0.17)), were found. (2) During post-Olympic
      light training, group A showed no significant amino acid changes. In contrast,
      group B recovered normal amino acid levels (glutamine 528 (41.4) micromol/l,
      histidine 76 (5.3) micromol/l, and total amino acids 2772 (165) micromol/l)
      (p<0.05 to p<0.001) to give a pattern comparable with that of group A, whereas,
      in group C, valine and threonine had increased (p<0.05), but glutamine (441
      (24.5) micromol/l) and histidine (58 (5.3) micromol/l) remained low. Thus none in
      group A, two in group B, but ten (53%) in group C still had plasma glutamine
      levels below 450 micromol/l, including eight of the 11 athletes who had presented
      with infection. (3) With the additional protein intake, virtually all persisting
      low glutamine levels increased to above 500 micromol/l. Plasma glutamine rose to
      592 (35.1) micromol/l and histidine to 86 (6.0) micromol/l. Total amino acids
      increased to 2761 (128) micromol/l (p<0.05 to p<0.001) and the amino acid pattern
      normalised. Six of the ten athletes on this protein intake returned to increased
      training within the three weeks. CONCLUSION: Analysis of these results provided
      contrasting plasma amino acid patterns: (a) a normal pattern in those without
      lasting fatigue; (b) marked but temporary changes in those with acute fatigue;
      (c) a persistent decrease in plasma amino acids, mainly glutamine, in those with
      chronic fatigue and infection, for which an inadequate protein intake appeared to
      be a factor.

PMID- 9562161
TI  - Heart rate response to "off-road" running events in female athletes.
AB  - INTRODUCTION: Despite the growing popularity of off-road running events, little
      information is available about the physiological stress of such activities. The
      demands of such events are unique in terms of the rough surface of the terrain
      encountered as well as the underfoot vegetation and the gradient. OBJECTIVES: The
      aim of this study was to investigate the physiological response of female
      athletes, as measured by heart rate, to three common off-road running events:
      cross country running (n = 15), fell running (n = 20), and orienteering (n = 25).
      METHODS: Heart rate responses were recorded during cross country and fell races,
      and orienteering by means of short range radiotelemetry. Road running (n = 21)
      was also studied as a reference. RESULTS: The mean heart rates for each event
      varied with the differing demands of the terrain. The highest (182 (10)
      beats/minute; mean (SD)) was for road running and the lowest (172 (10)
      beats/minute) for orienteering. Orienteering evoked a significantly more variable
      response than all other events (F4,100 = 112.4; p<0.01), with a range of 44
      beats/minute (142-186 beats/minute) in the heart rate. This may be due to both
      the variability of the terrain and the additional technical aspect of this sport.
      There was a positive trend in the slope of the regression lines of heart rate
      against time for both road and cross country running, which was not evident in
      the fell runners or the orienteers. The latter events demonstrated no consistent
      pattern. CONCLUSIONS: It is concluded that running off-road elicits a heart rate
      response that varies with the altering demands of surface, vegetation, and
      gradient.

PMID- 9562162
TI  - A five year physiological case study of an Olympic runner.
AB  - OBJECTIVE: To study physiological changes caused by long term endurance training
      in a world class female distance runner, and to compare these changes with
      alterations in 3000 m running performance. METHODS: The subject underwent regular
      physiological assessment during the period 1991-1995. Physiological measures made
      included body composition, maximal oxygen uptake (VO2MAX), running economy, and
      lactate threshold. In addition, the running speed at VO2MAX was estimated. Test
      protocols, laboratory equipment, and laboratory techniques used were the same for
      each test session. RESULTS: The 3000 m race performance improved by 8% from 1991
      to 1993 after which it stabilised. In contrast, VO2MAX fell from 1991 (73
      ml/kg/min) to 1993 (66 ml/kg/min). Submaximal physiological variables such as
      lactate threshold (from 15.0 to 18.0 km/h) and running economy (from 53 ml/kg/min
      to 48 ml/kg/min at 16.0 km/h) improved over the course of the study. Despite no
      increase in VO2MAX, the reduction in the oxygen cost of submaximal running caused
      the estimated running speed at VO2MAX to increase from 19.0 km/h in 1991 to 20.4
      km/h in 1995. CONCLUSIONS: Improvement in 3000 m running performance was not
      caused by an increase in VO2MAX. Rather, the extensive training programme
      adopted, together perhaps with physical maturation, resulted in improvements in
      submaximal fitness factors such as running economy and lactate threshold. These
      adaptations improved the running speed estimated to be associated with VO2MAX,
      and resulted in improved 3000 m running performance.

PMID- 9562163
TI  - Effects of deep and shallow water running on spinal shrinkage.
AB  - OBJECTIVES: Running in water has the potential to decrease the compressive forces
      on the spine as the body is supported. The aim of the study was to determine the
      magnitude of this loss in stature compared with running on land. METHODS:
      Fourteen runners completed three 30 minute runs on separate days in deep water,
      shallow water, and on a motor driven treadmill. During the three conditions,
      runners exercised at 80% of their exercise mode specific peak oxygen consumption.
      Subjects rested in the Fowler position for 20 minutes before and after exercise.
      Measurements of changes in stature were taken before resting, before running,
      after 15 minutes of running, after 30 minutes of running, and after the post
      exercise rest in the Fowler position. Changes in stature were recorded using a
      stadiometer accurate to 0.01 mm. RESULTS: Loss of stature values were 4.59
      (1.48), 5.51 (2.18), and 2.92 (1.7) mm (means (SD)) for running on the treadmill,
      and in shallow and deep water respectively. Running in deep water caused
      significantly lower creep than in the other trials (p<0.05), with no difference
      between the shallow water and treadmill conditions. Loss of stature was greater
      in the first half of the run for all conditions (p<0.05). Ratings of perceived
      exertion did not differ between the three exercise conditions. CONCLUSION:
      Results support the use of deep water running for decreasing the compressive load
      on the spine.

PMID- 9562164
TI  - Incidence of sporting injury in New Zealand youths aged 6-15 years.
AB  - OBJECTIVE: To document the incidence of injury in 6-15 year olds playing rugby
      union, rugby league, and netball, and to identify the common mechanisms, sites,
      severity, and time of injury. METHODS: Cross sectional data were collected by
      trained observers who watched 258 games of rugby union, netball, and rugby league
      over a four week period. The condition of the injured participants was monitored
      until recovery. RESULTS: In total, 5174 players were observed and an injury rate
      of 18 per 1000 player hours was calculated. Of all observed injuries, 29%
      required some form of medical treatment. A significant difference (p<0.05) in the
      distribution of injury over the four quarters of the games was recorded, most
      occurring in the first three quarters. In total, 81% of the injuries were
      classified as contact injuries, and these mainly occurred through direct contact
      with the opposition. Of all observed injuries, 27% were recurrent. CONCLUSIONS:
      The incidence of injury in rugby union, netball, and rugby league is low for
      children aged between 6 and 15 years relative to adult rates.

PMID- 9562165
TI  - Continuity and change in sporting and leisure time physical activities during
      adolescence.
AB  - OBJECTIVES: To map the pattern of involvement in physical activities by
      adolescents at ages 15 and 18 years. METHODS: Data from a longitudinal cohort
      study were used. Participants in the Dunedin Multidisciplinary Health and
      Development Study provided information about their sporting and similar physical
      activities during the 12 months before study assessments at ages 15 and 18 years.
      RESULTS: Total participation time at age 18 was 63% of that reported at age 15.
      Mean participation time for girls decreased from 7.5 hours a week to 4.3 hours a
      week (p<0.001) whereas for boys it decreased from 11.7 hours a week to 7.8 hours
      a week (p<0.001). At both ages, boys spent significantly more time in physical
      activity than girls. More time in physical activity at age 18 was reported by
      participants who judged their fitness higher than their peers (odds ratio (OR)
      1.7: 1.2, 2.5), those who played sport for their school (OR 1.8: 1.3, 2.4), and
      those reporting very good self assessed health (OR 1.4: 1.0, 1.8) at age 15. The
      overall median number of activities decreased from seven at age 15 to three at
      18. Boys were involved in more activities at age 15 but there was no sex
      difference at age 18 in the number of different activities reported. CONCLUSION:
      Although involvement in school sporting activities and high levels of fitness in
      mid-adolescence may protect against marked reductions in physical activity in
      late adolescence, social and organisational factors are also likely to be
      important. There is a need for innovative approaches to health promotion which
      will encourage adolescents to maintain higher levels of physical activity after
      they leave school.

PMID- 9562166
TI  - Effect of exercise on the proportion of unsaturated fatty acids in serum of
      untrained middle aged individuals.
AB  - OBJECTIVES: To examine whether prolonged moderate exercising by untrained middle
      aged individuals of both sexes affects the plasma ratio of unsaturated to
      saturated (U/S) fatty acids in the non-esterified fatty acid (NEFA) and
      triacylglycerol (TG) fractions. METHODS: Twenty two healthy untrained volunteers
      (eleven men and eleven pre-menopausal women), aged 35-55, exercised on bicycles
      at 50-55% maximal heart rate reserve (estimated 61% maximal oxygen uptake) for
      one hour. Pre- and post-exercise blood samples were analysed for lactate,
      glucose, glycerol, individual NEFAs and TG acyl groups, cholesterol, high density
      lipoprotein cholesterol, urea, cortisol, and testosterone. Biopsy specimens of
      adipose tissue were analysed for TG acyl group composition. RESULTS: Serum total
      NEFAs increased significantly whereas total TG decreased significantly in both
      sexes. Changes in individual fatty acids, in both the NEFA and TG fractions,
      generally paralleled changes in the total pool but were not proportionate. As a
      result, U/S NEFAs increased in both sexes, although significantly only in women.
      The shift was in the direction of the composition of the major source of blood
      NEFAs--that is, adipose tissue TG. U/S acyl groups of TG also increased in both
      sexes, although significantly only in men. CONCLUSIONS: Prolonged moderate
      exercise increases the U/S ratio of serum NEFAs and TG. This may add to the
      beneficial effects of exercise given the protective role of unsaturated fatty
      acids against coronary heart disease.

PMID- 9562168
TI  - Musings of a running "agony aunt".

PMID- 9562167
TI  - Effects of acute exercise on high density lipoprotein cholesterol and high
      density lipoprotein subfractions in moderately trained females.
AB  - Increases in high density lipoprotein cholesterol (HDL-C) levels have previously
      been reported after moderate exercise bouts lasting less than two hours in men.
      Little information exists, however, on HDL-C responses after moderate duration
      exercise in women. Post-exercise HDL-C modifications may appear differently in
      women because of higher baseline HDL-C concentrations and differences in
      lipolytic activity. To determine the influence of exercise on acute HDL-C
      responses in women, 12 trained premenopausal women (22 (4) years old; mean (SD))
      who ran 24-48 km a week exercised on a motor driven treadmill at 75% VO2MAX until
      3.34 MJ (800 kcal) were expended (72 (9) min). Subjects were all tested during
      the early follicular phase of their menstrual cycle. Fasting blood samples were
      obtained before exercise (baseline), immediately after (IPE), one hour after (1 h
      PE), 24 hours after (24 h PE), and 48 hours after (48 h PE) exercise. Plasma was
      analysed for HDL-C, HDL2-C, and HDL3-C. A significant increase in HDL-C was
      observed 48 h PE (p<0.05). HDL3-C increased IPE (p<0.01) but returned to baseline
      at 1 h PE. In contrast, HDL2-C was not significantly different from baseline at
      any time point. The rise in HDL-C, however, was attributed to an increase in both
      HDL2 and HDL3. Moreover, at 48 h PE, the increase in HDL-C correlated highly with
      changes in HDL2-C (r = 0.92). Thus it appears that exercise of moderate duration
      can elicit similar post-exercise increases in HDL-C in women to those previously
      reported in men. However, the changes in HDL subfractions leading to the rise in
      HDL-C may be different in women.

PMID- 9562169
TI  - Assessment of the flexibility of elite athletes using the modified Thomas test.
AB  - AIM: To analyse the modified Thomas test and obtain measures of flexibility for
      the iliopsoas, quadriceps and tensor fascia lata/iliotibial band. METHOD: The
      modified Thomas test was used to determine the range of flexibility of 117 elite
      athletes in tennis, basketball, rowing, and running. RESULTS AND CONCLUSION: The
      study has provided objective data for a clinical test measuring flexibility of
      the iliopsoas, quadriceps, and tensor fascia lata/iliotibial band. It is
      recommended that sufficient flexibility is obtained to perform a specific sport
      and that asymmetries between limbs are addressed.

PMID- 9562170
TI  - Bilateral anterior shoulder dislocations in bench pressing: an unusual cause.
AB  - A case of bilateral anterior glenohumeral dislocation in a young weight trainer
      is presented. The patient, an insurance clerk, had been using a free weight bar
      in the bench press position and had become tired when the weight on the bar
      forced his arms into hyperextension in the mid-abducted position. The humeral
      shaft gradually pivoted on the bench and the humeral heads were slowly dislocated
      anteriorly by the weight of the bar. Simple closed reduction under sedation was
      performed and there were no complications. After six weeks in bilateral broad arm
      slings, with pendulum exercises from two weeks, the patient began to mobilise his
      arms and he achieved a full range of movements. This unusual mechanism of injury
      has not previously been reported and we recommend that bench pressing should be
      performed with a weight that can be "locked" to prevent crushing of the user.
      Furthermore, the bench should be narrow enough to allow the shoulders to
      overhang, allowing greater extension in the abducted position without the arm
      pivoting on the edge of the bench.

PMID- 9562171
TI  - Post traumatic osteoma of tibial insertion of medial collateral ligament of knee
      joint.
AB  - Two cases are presented of post traumatic para-articular osteoma developing at
      the site of tibial attachment of the medial collateral ligament of knee joint.
      These occurred after injuries sustained while playing football and in one case
      the ossified mass was treated with surgical excision for unresolved symptoms
      after conservative measures. A comparison is made with Pellegrini Stieda disease,
      which is a similar affection of the femoral insertion of the medial ligament of
      the knee joint.

PMID- 9562172
TI  - Diaphragmatic rupture resulting from gastrointestinal barotrauma in a scuba
      diver.
AB  - A fit young man sustained a ruptured diaphragm during a recreational scuba dive
      three months after undergoing an uncomplicated laparoscopic Nissen fundoplication
      for gastro-oesophageal reflux disease. It is proposed that this rare occurrence
      was attributable to gastrointestinal barotrauma. The injury was treated by
      laparotomy, mobilisation of herniated abdominal viscera back into the abdomen,
      repair of the crura and gastropexy. He made a full postoperative recovery. It is
      concluded that scuba diving should be avoided in patients who have undergone
      fundoplication.

PMID- 9562173
TI  - The travelling athlete: issues relating to the Commonwealth Games, Malaysia,
      1998.

PMID- 9562175
TI  - What athletes often ask. Should I train when I have a cold and if not when can I
      return?

PMID- 9562174
TI  - Ligament injuries of the knee--limping forward?

PMID- 9562176
TI  - United Kingdom Sports Institute.

PMID- 9562177
TI  - Setting standards in sports medicine education.

PMID- 9562178
TI  - Physical activity data may be unsound.

PMID- 9562179
TI  - The United Kingdom Diploma in Sport and Exercise Medicine.

PMID- 9562180
TI  - Structural organization of the perivascular astrocyte endfeet and their
      relationship with the endothelial glucose transporter: a confocal microscopy
      study.
AB  - Despite the increasing evidence for a prominent role played by the perivascular
      endfeet of astrocytes in the functional metabolic coupling between astrocytes and
      neurons, a clear picture of their spatial organization is still lacking. To
      examine the three-dimensional structure of the astrocyte endfeet and their
      relationships with the endothelial cells, coronal rat brain sections
      immunolabeled for the two astroglial markers [glial fibrillary acidic protein
      (GFAP)/S-100beta] and the endothelial glucose transporter (GLUT1) were analyzed
      under the confocal microscope. Double immunolabeling of GFAP and S-100beta showed
      numerous well-defined astrocytes sending one or more endfeet to the vasculature.
      Examination of GFAP immunolabeling at higher magnification showed that these
      endfeet consist of well-defined rosette-like structures lying on the vessel wall.
      Double immunostaining of GFAP and GLUT1 showed that the endothelial cells were
      the main targets of these repeated geometrical units formed by the astrocyte
      endfeet. When three-dimensional images were reconstructed, obvious privileged
      anatomical relationships were observed between endfeet and individual endothelial
      cells. These anatomical data provide strong support for the involvement of
      astrocytes in cerebral metabolic coupling. The finger-like appearance of
      astrocyte endfeet could allow direct metabolic exchanges between intracerebral
      vessels and non-glial elements such as nerve terminals.

PMID- 9562181
TI  - Transient expression of neurofascin by oligodendrocytes at the onset of
      myelinogenesis: implications for mechanisms of axon-glial interaction.
AB  - Cell adhesion molecules (CAMs) must play a crucial role in both the initiation
      and signalling of axon-glial contact. However, the proteins that permit
      myelinating oligodendrocytes to recognize the axons that they ensheath in the
      developing CNS are unknown. By a subtractive cDNA library strategy, we have
      identified neurofascin as a powerful candidate for such a molecule. Neurofascin
      is strongly but transiently up-regulated in oligodendrocytes at the onset of
      myelinogenesis. Once oligodendrocytes have engaged their target axons the protein
      plays no further part, since the expression of the gene declines precipitously,
      in contrast to that of the major myelin component proteolipid protein, which
      remains elevated. After the initial surge of neurofascin expression in
      oligodendrocytes, there is a shift to a predominantly neuronal localization that
      persists into adulthood. Hence neurofascin in oligodendrocytes is unlikely to
      serve a function in the stabilization of the multilamellar sheath around the
      axon. The major neurofascin isoform of oligodendrocytes contains the third
      fibronectin type 3 (FNIII) repeat but lacks the mucin-like domain which supports
      the view that neurofascin isoforms are differentially expressed in the nervous
      system. Among the genes that are up-regulated during the terminal differentiation
      of the oligodendrocyte, neurofascin is unique in displaying a transient pattern
      of expression at the early stages of myelination. We propose that this CAM not
      only has a role in mediating axon recognition but also signals axonal contact
      through its links with the actin cytoskeleton.

PMID- 9562182
TI  - Increased axon growth through astrocyte cell lines transfected with urokinase.
AB  - The ability of cells to migrate through tissues depends on their production of a
      variety of proteases, and the same may be true of growth cones. Urokinase
      (plasminogen activator) regulates much of the extracellular proteolytic activity,
      by activating other proteases and as a result of its own proteolytic activity. In
      order to evaluate the potential role of urokinase as a promoter of axon growth,
      we have used a plasmid expressing urokinase under a cytomegalovirus promoter to
      transfect an astrocyte cell line, Neu7, which we have previously shown to provide
      a poor environment for axon regeneration. Five transfected lines all showed
      greatly increased ability to promote axon regeneration in both monolayer and
      three-dimensional cultures. The critical change in the transfected cells was
      largely within the extracellular matrix, since extracellular matrix laid down by
      urokinase-secreting cells was more permissive to axon growth than matrix from the
      parent Neu7 line. The effect was due to urokinase since treatment of the
      transfected cells with the urokinase inhibitors B623 and B428 rendered both the
      cells and their matrix much less permissive to axon growth, but did not require
      plasminogen, since it was blocked neither by serum-free medium nor by plasmin
      inhibitors.

PMID- 9562183
TI  - Effect of kainate on the membrane conductance of hilar glial precursor cells
      recorded in the perforated-patch configuration.
AB  - The effects of kainate on membrane current and membrane conductance were
      investigated in presumed hilar glial precursor cells of juvenile rats. The
      perforated-patch configuration was used also to reveal possible second-messenger
      effects. Kainate evoked an inward current that was accompanied by a biphasic
      change in membrane conductance in 69% of the cells. An initial conductance
      increase with a time course similar to that of the inward current was followed by
      a second delayed conductance increase. This second conductance was absent in
      whole-cell-clamp recordings, suggesting that it was mediated by a second
      messenger effect. Analysis of the reversal potentials of the membrane current
      during both phases of the kainate-induced conductance change revealed that the
      first conductance increase reflected the activation of AMPA receptors. Several
      lines of evidence suggest that the delayed second conductance increase was due to
      the indirect activation of Ca2+-dependent K+ channels via Ca2+-influx through
      AMPA receptors. (1) the delayed second conductance increase was blocked by Ba2+
      and the reversal of its underlying current was significantly shifted towards EK+,
      suggesting that it is due to the activation of K+ channels. (2) The delayed
      second conductance increase disappeared in a Ca2+-free saline buffered with
      BAPTA, indicating that it depended on Ca2+-influx. (3) Co2+, Cd2+ and nimodipine
      failed to block the delayed second conductance increase excluding a major
      contribution of voltage-dependent Ca2+ channels. (4) The involvement of
      metabotropic glutamate receptors also appeared unlikely, because the kainate
      induced delayed second conductance increase could not be blocked by a depletion
      of the intracellular Ca2+ stores with the Ca2+-ATPase inhibitor thapsigargin, and
      t-ACPD exerted no effect on membrane current and conductance. We conclude that
      kainate activates directly AMPA receptors in presumed hilar glial precursor
      cells. This results in a Ca2+ influx that could lead indirectly to the activation
      of Ca2+-dependent K+ channels.

PMID- 9562184
TI  - Serotoninergic control of the activity and expression of glial GABA transporters
      in the rat cerebellum.
AB  - Gamma-Aminobutyric acid (GABA) transporters (GAT-1, GAT-2, and GAT-3) play a key
      role in the termination of GABA transmission and the regulation of extracellular
      GABA concentrations. In the present study, pharmacological, cellular, and
      molecular analyses provide evidence for a modulatory effect of serotoninergic
      neurons on the activity and expression of glial GABA transporters in the rat
      cerebellum. Degeneration of serotoninergic neurons after in vivo 5,7
      dihydroxytryptamine (5,7-DHT) treatment resulted in a significant decrease (-27%)
      in [3H]-GABA uptake into cerebellar punches. This decrease probably occurred via
      inhibition of GAT-2 or GAT-3 activity since their inhibitor, beta-alanine,
      induced a decrease in [3H]-GABA uptake in punches of sham-operated rats (-28%),
      but not in punches of 5,7-DHT-treated rats, demonstrating that serotonin terminal
      degeneration had already impaired the beta-alanine-sensitive component of GABA
      uptake. In contrast, nipecotic acid, a preferential inhibitor of GAT-1, induced
      comparable decreases in [3H]-GABA uptake comparable in punches of 5,7-DHT (-38%)
      versus sham-operated rats (-37%). The decreases in GAT-1 (-16%), GAT-2 (-34%),
      and GAT-3 (-32%) mRNA levels after 5,7-DHT treatment (detected by quantitative RT
      PCR) are consistent with a serotoninergic control of GABA transporter expression
      at the transcriptional level. The cellular distribution of GAT-2 and GAT-3 mRNA,
      shown by in situ hybridization, suggests a glial localization of these
      transporters in the cerebellum and demonstrated a preferential anatomical
      localization of GAT-2 mRNA in the granular layer and of GAT-3 mRNA in the deep
      cerebellar nuclei. A direct serotoninergic control of glial GABA uptake was
      further demonstrated in vitro since serotonin stimulated the activity and mRNA
      expression of the GABA transporters in cerebellar astrocyte cultures.

PMID- 9562185
TI  - Retinal axon regeneration in the lizard Gallotia galloti in the presence of CNS
      myelin and oligodendrocytes.
AB  - Retinal ganglion cell (RGC) axons in lizards (reptiles) were found to regenerate
      after optic nerve injury. To determine whether regeneration occurs because the
      visual pathway has growth-supporting glia cells or whether RGC axons regrow
      despite the presence of neurite growth-inhibitory components, the substrate
      properties of lizard optic nerve myelin and of oligodendrocytes were analyzed in
      vitro, using rat dorsal root ganglion (DRG) neurons. In addition, the response of
      lizard RGC axons upon contact with rat and reptilian oligodendrocytes or with
      myelin proteins from the mammalian central nervous system (CNS) was monitored.
      Lizard optic nerve myelin inhibited extension of rat DRG neurites, and lizard
      oligodendrocytes elicited DRG growth cone collapse. Both effects were partially
      reversed by antibody IN-1 against mammalian 35/250 kD neurite growth inhibitors,
      and IN-1 stained myelinated fiber tracts in the lizard CNS. However, lizard RGC
      growth cones grew freely across oligodendrocytes from the rat and the reptilian
      CNS. Mammalian CNS myelin proteins reconstituted into liposomes and added to
      elongating lizard RGC axons caused at most a transient collapse reaction. Growth
      cones always recovered within an hour and regrew. Thus, lizard CNS myelin and
      oligodendrocytes possess nonpermissive substrate properties for DRG neurons--like
      corresponding structures and cells in the mammalian CNS, including mammalian-like
      neurite growth inhibitors. Lizard RGC axons, however, appear to be far less
      sensitive to these inhibitory substrate components and therefore may be able to
      regenerate through the visual pathway despite the presence of myelin and
      oligodendrocytes that block growth of DRG neurites.

PMID- 9562186
TI  - Partial peripheral nerve injury leads to activation of astroglia and microglia
      which parallels the development of allodynic behavior.
AB  - Three different cell markers were studied in rats to note changes in the
      immunoreactivity (IR) in the lumbar spinal cord 1 to 84 days following partial
      sciatic nerve ligation (PSNL). Alteration in average IR were studied for
      complement receptor C3bi (OX42; microglia), major histocompatibility complex II
      (OX6; microglia), and glia fibrillary acidic protein (GFAP; astroglia). Thirty
      four female rats underwent ligation of approximately 1/2 of the sciatic nerve
      (PSNL). This injury resulted in the development of mechanical allodynia, which
      was quantitated by the measurement of foot withdrawal threshold to the
      application of Von Frey filaments. Ipsilateral increase in IR of OX42 and GFAP
      was observed to occur within 2 days, maximized by day 14, and did not return to
      contralateral spinal gray matter IR levels by day 84 (time period of study).
      Increases in OX42 IR and GFAP IR were observed within the spinal segments
      innervated by the sciatic nerve. GFAP IR was not expressed in all lumbar
      segments. OX42 staining with the upper portion of the dorsal horn was found to
      localize within the areas of deafferentation demonstrated by loss of thiamine
      monophosphatase activity within the substantia gelatinosa. OX6 IR was only seen
      in a few cells within the ipsilateral gray matter, indicating that microglia did
      not become phagocytic. Both GFAP IR and OX42 IR were found to linearly correlate
      with allodynic behavior with OX42 IR being more statistically significant.
      Correlation of OX42 IR in only the upper portion of the dorsal horn (not
      including the neck) resulted in an even a greater level of significance. These
      findings demonstrate that microglia and astroglia are activated following PSNL
      and that their increase in IR correlates with the development of allodynic
      behavior.

PMID- 9562187
TI  - Tracing of fluoro-gold prelabeled microglia injected into the adult rat brain.
AB  - In light of a recent interest in the transplantation of cultured microglial
      cells, we have examined the use of the fluorescent dye Fluoro-Gold (FG) as a
      tracer for these cells. Following injection into the adult rat brain, FG
      prelabeled microglial cells were readily traceable for up to 2 weeks with minimal
      labeling of endogenous cell populations. Some of the injected cells
      differentiated into ramified microglial cells as a result of exposure to the
      adult CNS environment. Injection of free FG into the adult rat brain resulted in
      the widespread labeling of neurons and perivascular cells, but not endogenous
      microglial cells, indicating that perivascular cells, but not resting microglia,
      are actively pinocytotic cells of the CNS. Our results show that FG is an
      effective label for the tracing of transplanted microglial cells.

PMID- 9562188
TI  - Subcutaneous naloxone: a less rude awakening?

PMID- 9562189
TI  - Thermal characteristics of neutralization therapy and water dilution for strong
      acid ingestion: an in-vivo canine model.
AB  - OBJECTIVE: To determine whether in-vivo neutralization therapy for acid
      ingestions will superimpose a thermal injury upon tissue already damaged by acid.
      METHODS: An in-vivo canine model was used with repeated measures of tissue and
      luminal temperatures. All dogs were placed under halothane general anesthesia.
      The stomach was exteriorized and temperature probes were placed in the lumen and
      mucosa. 25 mL of 0.5 N HCl (25 degrees C) was placed in the gastric lumen
      followed 5 minutes later by 75 mL of either 8% NaHCO3 neutralization (25 degrees
      C, n = 10) or water dilution (25 degrees C, n = 10). Temperature measurements
      were recorded at specified intervals for 5 minutes post HCl acid exposure and for
      30 minutes post treatment. Temperature profiles were analyzed by repeated
      measures ANOVA. Post-treatment changes were evaluated using signed-rank tests.
      RESULTS: In both treatment groups, treatment resulted in significant decreases in
      initial mucosa and intraluminal temperatures. Both the mucosa and intraluminal
      temperatures decreased immediately after treatment with HCO3 by an average of 1.6
      degrees C (p = 0.05). In the water dilution treatment group, both temperatures
      decreased by 1.1 degrees C (p = 0.05). Ensuing post-treatment temperatures
      increased but did not reach baseline temperatures at any time up to 30 minutes
      post treatment. CONCLUSIONS: In the in-vivo setting, there is no evidence of
      hazardous temperature elevation when a weak alkali or dilution therapy is used to
      neutralize strong acid-induced injury. Contraindication of this form of emergency
      treatment should not be based on the preconceived idea that a resultant
      exothermic reaction will cause a superimposed thermal injury. Further clinical
      study is needed to determine the clinical utility of this emergency therapeutic
      modality.

PMID- 9562190
TI  - Intravenous vs subcutaneous naloxone for out-of-hospital management of presumed
      opioid overdose.
AB  - OBJECTIVE: To determine whether naloxone administered i.v. to out-of-hospital
      patients with suspected opioid overdose would have a more rapid therapeutic onset
      than naloxone given subcutaneously (s.q.). METHODS: A prospective, sequential,
      observational cohort study of 196 consecutive patients with suspected opioid
      overdose was conducted in an urban out-of-hospital setting, comparing time
      intervals from arrival at the patient's side to development of a respiratory rate
      > or =10 breaths/min, and durations of bag-valve-mask ventilation. Subjects
      received either naloxone 0.4 mg i.v. (n = 74) or naloxone 0.8 mg s.q. (n = 122),
      for respiratory depression of <10 breaths/min. RESULTS: Mean interval from crew
      arrival to respiratory rate > or =10 breaths/min was 9.3 +/- 4.2 min for the i.v.
      group vs 9.6 +/- 4.58 min for the s.q. group (95% CI of the difference -1.55,
      1.00). Mean duration of bag-valve-mask ventilation was 8.1 +/- 6.0 min for the
      i.v. group vs 9.1 +/- 4.8 min for the s.q. group. Cost of materials for
      administering naloxone 0.4 mg i.v. was $12.30/patient, compared with
      $10.70/patient for naloxone 0.8 mg s.q. CONCLUSION: There was no clinical
      difference in the time interval to respiratory rate > or =10 breaths/min between
      naloxone 0.8 mg s.q. and naloxone 0.4 mg i.v. for the out-of-hospital management
      of patients with suspected opioid overdose. The slower rate of absorption via the
      s.q. route was offset by the delay in establishing an i.v.

PMID- 9562191
TI  - Serum creatine kinase is an unreliable predictor of ectopic pregnancy.
AB  - OBJECTIVE: To compare serum creatine kinase (CK) values in patients with ectopic
      pregnancy vs patients with threatened miscarriage or normal pregnancy. METHODS:
      An observational case-control study was performed at an urban teaching hospital.
      Pregnant women with a quantitative beta-hCG obtained for suspicion of ectopic
      pregnancy were evaluated. Excluded were cases with recent trauma, i.m.
      injections, surgery, or history of heart, liver, or muscle disease. The serum
      beta-hCG and CK values were recorded and compared between groups with 1-way ANOVA
      and Tukey's multiple comparison procedure at the overall 0.05 level. RESULTS: The
      15 ectopic, 28 threatened miscarriage, and 21 normal pregnancy cases were of
      similar gestational ages (p = 0.2), ranging from 3 to 12 weeks. Although the CK
      values for ectopic pregnancy (88.8 +/- 33.6 IU/L) exceeded those for threatened
      miscarriage (65.9 +/- 59.0 IU/L) and normal pregnancy (56.0 +/- 38.1 U/L) (p =
      0.02), there was significant overlap between groups. CK values were at or above a
      cutoff of 74 IU/L in 80% (95% confidence interval: 52-96%) of ectopic
      pregnancies, 25% (11-45%) of threatened miscarriages, and 14% (3-36%) of normal
      pregnancies. CONCLUSIONS: Although the ectopic pregnancy population is
      characterized by a higher mean CK than are patients with threatened miscarriage
      or a normal pregnancy, a significant overlap in CK values makes use of this serum
      marker unreliable for detecting ectopic pregnancy.

PMID- 9562192
TI  - The ability of a single serum progesterone value to identify abnormal pregnancies
      in patients with beta-human chorionic gonadotropin values less than 1,000 mIU/mL.
AB  - OBJECTIVE: To determine the test performance of a single serum progesterone value
      <5.0 ng/mL for detecting ectopic pregnancy or other abnormal pregnancies in
      symptomatic ED patients with beta-hCG levels <1,000 mIU/mL. METHODS: A
      prospective study of progesterone levels was performed in consecutive ED patients
      presenting to an urban teaching hospital from December 1995 to March 1997 with
      abdominal pain and/or vaginal bleeding, a positive qualitative beta-hCG, and a
      quantitative beta-hCG value <1,000 mIU/mL. Patients were excluded if they were
      status-post a dilatation and evacuation procedure, had insufficient serum to run
      the progesterone assays, or were lost to follow-up. Progesterone values were
      measured from the original beta-hCG sample. Final patient diagnosis was
      abstracted from hospital records. RESULTS: 127 patients met eligibility criteria.
      39 patients were excluded, leaving a total of 88 enrolled patients. 76 patients
      with abnormal pregnancies were identified [9 ectopic pregnancies, 62 abnormal
      intrauterine pregnancies (IUPs), 5 abnormal IUPs vs ectopic pregnancies], 71 of
      whom had progesterone values <5.0 ng/mL [sensitivity 71/76 (94%), 95% CI 86-98%].
      12 patients with normal pregnancies were identified, all of whom had progesterone
      values > or =5.0 ng/mL [specificity 12/12 (100%), 95% CI 78-100%]. CONCLUSION: A
      single progesterone value <5.0 ng/mL has high sensitivity and specificity in
      detecting abnormal pregnancy in symptomatic ED patients with beta-hCG values
      <1,000 mIU/mL.

PMID- 9562194
TI  - Subclassification of indeterminate pelvic ultrasonograms: stratifying the risk of
      ectopic pregnancy.
AB  - OBJECTIVE: To determine whether the subclassification of indeterminate ultrasound
      readings can identify patients who are at high, intermediate, or low risk for
      ectopic pregnancy. METHODS: A retrospective review was made of consecutive ED
      patients presenting to an urban teaching hospital from August 1991 to December
      1994 with abdominal pain and/or vaginal bleeding and a positive beta-hCG.
      Patients who had transvaginal ultrasonograms obtained during the ED visit that
      were read as indeterminate (no extrauterine findings of ectopic pregnancy and no
      intrauterine fetal pole or yolk sac) were eligible. Ultrasonograms were
      subclassified into 5 groups (empty uterus, nonspecific intrauterine fluid,
      echogenic debris within endometrial cavity, abnormal sac, normal sac) based on
      predetermined criteria. Patients were excluded if the final diagnosis could not
      be definitively determined. RESULTS: 248 patients were identified. 20 patients
      were excluded because a final diagnosis could not be determined. Patients with an
      empty uterus [25/94 = 27% (95% CI 18-36%)] had the highest frequency of ectopic
      pregnancy. Patients with nonspecific intrauterine fluid collections [4/30 = 13%
      (95% CI 4-31%)] had the next highest frequency of ectopic pregnancy. Patients
      with intrauterine echogenic debris [2/39 = 5% (95% CI 1-11%)], abnormal sacs
      [1/36 = 3% (95% CI 1-9%)], or normal-appearing sacs [0/29 = 0% (95% CI 0-8%)] had
      low frequencies of ectopic pregnancy. CONCLUSION: Subclassification of
      indeterminate ultrasound readings identifies patients at high, intermediate, or
      low risk for ectopic pregnancy and should improve the diagnostic accuracy of
      ultrasonography in patients at risk for ectopic pregnancy.

PMID- 9562193
TI  - Serum progesterone and endovaginal sonography by emergency physicians in the
      evaluation of ectopic pregnancy.
AB  - OBJECTIVE: To determine a discriminatory level for serum progesterone (SP) in
      pregnant patients with no definite intrauterine pregnancy (IUP) on endovaginal
      ultrasonography (US) in the differentiation of ectopic pregnancy from normal
      IUPs. METHODS: A prospective observational study in a convenience sample of women
      at risk for ectopic pregnancy was performed at an urban teaching hospital from
      May 1991 until May 1994. Women aged > or =18 years presenting to the ED with a
      positive pregnancy test in combination with pelvic or abdominal pain, vaginal
      bleeding, orthostasis, adnexal mass or tenderness, or any historical risk factor
      for ectopic pregnancy were eligible. Hypotensive or unstable patients were
      excluded. Endovaginal US was performed and patients with no definite IUP had a
      serum beta-hCG and SP measured. RESULTS: 314 patients were enrolled, with 14
      excluded for lack of follow-up or incomplete SP data, yielding 300 patients. The
      initial endovaginal US diagnoses included 169 definite IUP, 31 abnormal IUP, 5
      definite ectopic pregnancy, and 95 no definite IUP. 68/95 had SP measured, with
      values of 22.8 +/- 13.4 ng/mL (mean +/- SD) for IUP; 4.9 +/- 6.5 for spontaneous
      abortion, and 7.5 +/- 7.2 for ectopic pregnancy. The mean values were
      significantly different (2-tailed t-test) for ectopic pregnancy vs IUP and for
      spontaneous abortion vs IUP. An SP of > or =11 ng/mL (sensitivity 91%;
      specificity 84%) was post hoc the best cutoff value for suggesting an IUP when
      the endovaginal US was not definite for IUP. CONCLUSIONS: SP cannot reliably
      discriminate ectopic pregnancy vs spontaneous abortion in pregnant patients with
      no definite IUP on endovaginal US; however, a low SP (<11 ng/mL) in this
      sonographic category suggests an abnormal pregnancy.

PMID- 9562195
TI  - Gas exchange and lung mechanics during percutaneous transtracheal ventilation in
      an unparalyzed canine model.
AB  - OBJECTIVE: To compare the efficacy of percutaneous transtracheal ventilation
      (PTV) in the unparalyzed state with that in the paralyzed state using a sedated
      nonobstructed canine model. METHODS: Eight mongrel dogs (16.8-32 kg) were
      anesthetized, instrumented, and placed in a volume plethysmograph. Anesthesia was
      achieved with pentobarbital sodium (up to 30 mg/kg). The spontaneous respiratory
      drive was kept intact. PTV was performed using a 13-ga transtracheal catheter and
      compressed air at 45 psi at an I:E ratio of 1:3 (15 breaths/min). Each dog was
      sequentially ventilated in both the paralyzed and unparalyzed states. The
      paralyzed/unparalyzed sequence was alternated among the animals to avoid sequence
      bias. Paralysis was achieved with succinylcholine (0.1 mg/kg bolus and 0.01
      mg/kg/min drip). Reversal of paralysis was achieved by discontinuing the
      succinylcholine infusion. Key variables, including arterial blood gas, tidal
      volume, and pulmonary mechanics, were measured and compared for the paralyzed and
      unparalyzed states. RESULTS: Gas exchanges and lung mechanics were similar
      between the unparalyzed and paralyzed states. There was no significant difference
      in mean pH, pCO2, pO2, tidal volume, or peak inspiratory transpulmonary pressure.
      There was also no significant difference in pulmonary resistance or pulmonary
      compliance. CONCLUSION: In a sedated nonobstructed canine model, PTV is as
      efficacious in the unparalyzed state as it is in the paralyzed state. The lung
      mechanics are also similar in the 2 states. These data suggest that it may be
      unnecessary to induce paralysis when using PTV for emergency ventilation in the
      heavily sedated state.

PMID- 9562196
TI  - Relationships between ambulance transports for alcohol intoxication and assault.
AB  - OBJECTIVE: To evaluate the association between ambulance transports for assault
      and those for alcohol intoxication. METHODS: A retrospective analysis of
      emergency medical services (EMS) calls was performed. The authors used logistic
      regression models to compare patients transported for alcohol intoxication with a
      control group of patients transported for respiratory distress (asthma or
      shortness of breath) with respect to whether they had been transported on a
      separate occasion for a chief complaint of assault. RESULTS: Patients transported
      for alcohol intoxication had 9 times the risk of transport for assault as
      compared with the control group (OR = 9.3; 95% CI = 6.4, 13.6). The odds of
      transport for assault among the alcohol patients increased 17.1% with each
      alcohol transport (OR = 1.17; 95% CI = 1.14, 1.20) but decreased for the control
      group (OR = 0.34; 95% CI = 0.26, 0.44). Repeat transports for assault were more
      common among the alcohol patients than among the control group (OR = 3.3; 95% CI
      = 1.1, 11.3). The mean number of assault transports was higher among the alcohol
      patients than among the patients never transported for alcohol intoxication (p <
      0.0001). CONCLUSIONS: Patients transported on multiple occasions for acute
      alcohol intoxication are at relatively high risk for assault. This risk group
      should be targeted for focused assault prevention interventions that include
      components designed to reduce incidents of repeat alcohol intoxication.

PMID- 9562197
TI  - Payment of emergency department bills by Medicaid patients.
AB  - OBJECTIVE: To analyze ED services used by and payment received from patients who
      request to stay and assume responsibility for their bills after being denied
      emergency care payment by their Medicaid providers. METHODS: A retrospective
      chart review over an 18-month period was conducted. Charges for these visits were
      obtained from the physician billing service and hospital finance records.
      RESULTS: Of 193 patient visits identified, 192 charts were located and reviewed
      for chief complaint, diagnostic tests, and interventions performed. In total, the
      visits resulted in $18,120 in physician charges and $28,126 in hospital charges.
      Three payments amounting to $134 were collected, leaving $46,246 in nonreimbursed
      charges. CONCLUSIONS: Nearly all patients who elect to be seen in this pediatric
      ED after being denied by their Medicaid managed care providers do not pay their
      bills. ED resources, including laboratory studies, radiographs, and
      consultations, are used to evaluate and treat these patients without
      compensation. The cost of this nonreimbursed care must be recovered from other
      patient care charges.

PMID- 9562198
TI  - Physicians in rural West Virginia emergency departments: residency training and
      board certification status.
AB  - OBJECTIVE: To describe the training and certification of physicians who staff
      small EDs in rural West Virginia. METHODS: A survey of rural hospital-based EDs
      was performed. The authors chose to study all hospitals in counties with
      populations of <30,000 and in which the hospital was the only one in the county.
      Interviews were conducted with the medical director of the ED or the hospital
      administrator, depending on who was available at the time of interview. Data
      collected describing the emergency physicians (EPs) employed at each facility
      included: medical school and residency training, specialty board certification,
      and certification in a variety of life support courses. General information about
      each ED, such as census and hospital resources, was also obtained. Interview data
      were collected on a survey form and subsequently entered into a database.
      Descriptive analyses were performed. RESULTS: 20 hospitals met rural criteria for
      inclusion in the study and all were included. The median number of full-time
      physicians per ED was 2 (IQR 2-4). 98 part-time doctors were identified; 28 (29%)
      of these were residents in training. 13/40 (33%) of full-time and 37/98 (38%) of
      part-time physicians were foreign medical graduates. Only 3/40 (7.5%) of full
      time EPs completed residency training in emergency medicine (EM). Only 4/98 (4%)
      of part-time EPs were residency-trained in EM. 50% of full-time EPs were board
      certified in a primary care specialty. Only 5/42 (12%) of full-time EPs were
      board-certified in EM. One third of full-time and the majority of part-time EPs
      were not board-certified in any specialty whatsoever. The majority of EPs had
      been certified in Advanced Cardiac Life Support, but fewer had been certified in
      Advanced Trauma Life Support and/or Pediatric Advanced Life Support/Advanced
      Pediatric Life Support. CONCLUSIONS: The majority of physicians staffing small
      rural EDs in West Virginia are neither residency-trained nor board-certified in
      EM. Further studies are warranted to determine the most efficient and effective
      way to maximize the skills and availability of emergency care providers in rural
      settings.

PMID- 9562199
TI  - The false-positive rate of thoracic outlet syndrome shoulder maneuvers in healthy
      subjects.
AB  - OBJECTIVE: To estimate the incidence of false-positive findings of thoracic
      outlet syndrome (TOS) shoulder maneuvers, Adson's test (AT), costoclavicular
      maneuver (CCM), elevated arm stress test (EAST), and supraclavicular pressure
      (SCP) in healthy subjects. METHODS: A cross-sectional, observational study was
      performed in a medical school and affiliated emergency medicine residency program
      setting. Participants included healthy adult volunteers without symptoms of TOS.
      The shoulder maneuvers AT, CCM, EAST, and SCP were performed in randomized order
      for 30 sec, 30 sec, 3 min, and 30 sec, respectively. Pulse quality and the
      presence and timing of pain or paresthesias were assessed. RESULTS: 53 subjects
      were enrolled, including 27 women, aged 29.7 +/- 6.4 years (range 21-58 years).
      AT, CCM, EAST, and SCP resulted in an altered pulse in 11%, 11%, 62%, and 21%;
      pain in 0%, 0%, 21%, and 2%; and paresthesias in 11%, 15%, 36%, and 15% of cases,
      respectively. The following outcomes had reasonable false-positive rates (upper
      95% confidence limit): pain with the AT (7%), CCM (7%), SCP (10%), or any 2 TOS
      shoulder maneuvers (10%); discontinuing the EAST because of symptoms (16%); or
      any symptom with 3 (13%) or 4 (7%) TOS shoulder maneuvers. CONCLUSIONS: In a
      study of TOS shoulder maneuvers in healthy subjects, the outcomes of pulse
      alteration or paresthesias were unreliable in general. However, TOS shoulder
      maneuvers have reasonably low false-positive rates when a positive outcome is
      defined as pain after AT, CCM, or SCP; discontinuation of the EAST secondary to
      pain; pain in the same arm with > or =2 maneuvers; or any symptom in the same arm
      with > or =3 maneuvers.

PMID- 9562200
TI  - University and community hospital medical student emergency medicine clerkship
      experiences.
AB  - OBJECTIVE: To determine whether there is a significant difference between
      educational opportunities for fourth-year medical students rotating at a
      university hospital (UH) compared with several community hospitals (CHs) during a
      mandatory emergency medicine (EM) clerkship. METHODS: A self-reported clinical
      tool was completed in real time by each student rotating for 2 weeks at the UH
      and 2 weeks at 1 of 4 CHs (3 affiliated and 1 unaffiliated). Students are
      required to document the number of patients seen and the number of procedures
      performed on each of 20 six-hour shifts. They rated the EM attending clinical
      teaching by site using a 5-point scale at the end of the clerkship. RESULTS: Most
      (95%) of the 87 students in the 7 clerkship blocks of the 1996-97 academic year
      rotated at the UH and a CH. Most (71%) students rated both the UH and the CH for
      the quality of teaching by attendings. There was a significant difference in the
      mean number of patients evaluated/shift (2.2 +/- 0.10 vs 2.8 +/- 0.10, UH vs CH;
      p < 0.001) and the mean number of procedures performed/shift (0.36 +/- 0.04 vs
      0.56 +/- 0.05, UH vs CH; p < 0.001). Attending clinical teaching scores were
      significantly higher (p = 0.03) at the CHs. CONCLUSIONS: The educational
      opportunities for students in an EM clerkship to evaluate patients and perform
      procedures were significantly greater at the community hospitals. Inclusion of
      community hospital settings in a medical student EM clerkship may optimize the
      clinical experience.

PMID- 9562201
TI  - Clinical Pearls: Fever and facial swelling. Buccal cellulitis.

PMID- 9562202
TI  - Definition of emergency medicine.
AB  - This SAEM position paper clarifies the role of emergency medicine in health care
      delivery. It builds upon the working definition of emergency medicine developed
      by the American College of Emergency Physicians in 1994 by describing the health
      care role of emergency physicians (EPs). EPs are first-contact providers who care
      for all patients regardless of age, gender, time of presentation, or ability to
      pay. They remain the only continuously accessible specialty for patients seeking
      help and solace in the health care system. They are an essential link in the
      health care continuum between primary care physicians, specialists, the out-of
      hospital system, the patient, inpatient services, and communication services. The
      EP's role is in organizing and monitoring the emergency care delivery system.
      Part of this role is to better align the health care provider training and
      ability with the specific medical needs of a patient. The emergency health care
      system remains the essential medical safety net for all individuals needing care
      in this country.

PMID- 9562203
TI  - Ensuring the chain of recovery for stroke in your community.
AB  - Until recently, the prehospital and ED management of nonhemorrhagic stroke was
      largely supportive care. Studies have now demonstrated the potential of certain
      therapeutic interventions to reverse the debilitating consequences of such
      strokes. The clinical benefit for such interventions and the risk of significant
      therapeutic complications are highly time-dependent. To optimize the chances of a
      better outcome for the patient with stroke, each community must establish and
      continue to refine a chain of recovery for stroke patients. The chain of recovery
      is a metaphor that describes a series of sequential actions that must take place
      in a timely fashion to optimize the chances of recovery from stroke. Each of
      these sequential actions forms an individual link in the chain, and each link
      must be intact. The links include: identification of the onset of stroke symptoms
      by the patient or bystanders; dispatch life support services, which preferably
      include enhanced 9-1-1 and medically supervised and trained dispatchers who can
      rapidly deploy the closest responders and transport units; emergency medical
      services (EMS) personnel who can rapidly assess and transport the stroke patient
      to the closest appropriate center capable of providing advanced stroke
      diagnostics and interventions; en route notification of the receiving facility so
      that appropriate personnel can be readied for rapid diagnosis and intervention;
      and receiving facilities capable of providing rapid diagnosis and advanced
      treatment of stroke, including the availability of specialists who can evaluate
      underlying etiologies as well as plan future therapies and rehabilitation. To
      ensure that the chain of recovery is in place, aggressive public education
      campaigns should be implemented to increase the probability that stroke symptoms
      and signs will be recognized as soon as possible by patients and bystanders. In
      addition, because most of the current training programs for EMS dispatchers and
      EMS personnel are lacking with regard to stroke, it is recommended that such
      personnel and their EMS system managers be updated on current management and
      treatment strategies for stroke.

PMID- 9562204
TI  - Emergency medicine and the development of the Food and Drug Administration's
      final rule on informed consent and waiver of informed consent in emergency
      research circumstances.
AB  - This article reviews the federal regulations for emergency and acute
      resuscitation research in effect prior to October 1996, the historical issues
      that contributed to the development of these regulations, the controversies that
      arose surrounding the application of these regulations to emergency research
      circumstances, and the methods by which the regulations were changed. The new
      regulations introduced by the U.S. Food and Drug Administration (FDA) also are
      reviewed.

PMID- 9562205
TI  - Normal saline vs lactated Ringer's solution for ocular irrigation.

PMID- 9562206
TI  - How objective is medical practice?

PMID- 9562207
TI  - Specialty training and the personal use of benzodiazepines by physicians affect
      their proneness to prescribe tranquilizers.
AB  - The decision on how to treat a patient does not depend on clinical matters or
      illness characteristics alone, but also on patient, physician and setting
      variables such as personality, training, or reimbursement. No research has yet
      been carried out to answer the question whether personal experience with
      medications also influences prescribing behavior. In this study, 124 physicians
      stratified according to specialty (neuropsychiatrists vs. general practitioners),
      type of institution (private practice vs. hospital), years of professional
      experience (young vs. old), and region (rural vs. urban) participated in a
      structured interview to evaluate their proneness to prescribe benzodiazepines for
      sleep disorders as well as their personal experience in taking benzodiazepines
      for their own sleep problems. Both specialty and personal experience were
      significantly related to proneness to prescribe. Other variables tested (region,
      institution, age, gender) did not help to explain the variance in benzodiazepine
      prescribing practice. Thus physician variables and, importantly, their own
      personal experience in taking the medication significantly influence treatment
      choice. Rational medical decision making and treatment guidelines must therefore
      take into account medical knowledge as well as knowledge of personal treatment
      preferences and professional biases.

PMID- 9562208
TI  - Morning fluoxetine plus evening mianserin versus morning fluoxetine plus evening
      placebo in the acute treatment of major depression.
AB  - In a randomized clinical study the combination of fluoxetine 20 mg daily and
      mianserin 30 mg daily was compared to fluoxetine 20 mg daily and a mianserin
      placebo. In total, 34 patients with major depression were randomized, of whom 16
      received fluoxetine plus mianserin; 18 patients received fluoxetine plus placebo.
      Of these patients, 69% completed the planned trial of six weeks in the fluoxetine
      plus mianserin group while 61% completed in the fluoxetine plus placebo group. In
      the efficacy analysis (excluding dropouts from the first two weeks of treatment)
      the combination of fluoxetine and mianserin was superior to fluoxetine and
      placebo both in observer ratings of depression and in quality of life ratings.
      However, in the intention-to-treat analysis this difference was not statistically
      significant. No major side effects were reported. After four weeks of treatment
      headache was most often seen in the fluoxetine and mianserin combination, while
      sweating was most often seen in the fluoxetine plus placebo group. No
      pharmacokinetic interaction in terms of fluoxetine plasma levels was found in the
      mianserin-treated patients.

PMID- 9562209
TI  - Effects of Lorazepam on the automatic online evaluation of sleep EEG data in
      healthy volunteers.
AB  - In earlier publications we described an automatic algorithm to detect rapid eye
      movement (REM) sleep from a single-channel EEG recording without using EMG or EOG
      information. This system consisted of an artificial neural network operating on
      the basis of preprocessed EEG data and was composed to provide a maximum of
      robustness for online applications. In the present study the influence of acute
      administration of lorazepam on the performance of the REM detection procedure was
      evaluated. Following an adaptation to laboratory conditions, sleep EEG data were
      obtained from healthy subjects in three nights each. On the evening of the second
      night the volunteers received a single dosage of 2.5 mg Lorazepam; the other two
      nights were drug-free. The sleep profile and the quantitative EEG data reflected
      the known changes following acute administration of benzodiazepines: during the
      treatment night the amount of non-REM sleep and the relative power of the EEG
      signal in the beta and gamma frequency bands was increased relative to the first
      night, while the amount of REM sleep was reduced. The night of drug
      discontinuation still showed some characteristics of the treatment night. The
      discordance rate of the REM detection algorithm relative to the manual evaluation
      ranged from 9% to 14.2% for the different nights. Surprisingly, the percentage of
      correctly classified time periods was even higher for the lorazepam night as
      compared to the other nights.

PMID- 9562210
TI  - Are psychoactive-drug-induced changes in plasma lipid and lipoprotein levels of
      significance for clinical remission in psychiatric disorders?
AB  - In the present pilot study, our aim was to investigate whether associations could
      be demonstrated in psychiatric patients between the changes in plasma lipid and
      lipoprotein levels expected during treatment with psychoactive drugs and the
      changes in the patients' depressive and hostile behavior. One hundred and
      fourteen patients with various psychiatric disorders (depressive episode in
      bipolar affective disorder, depressive episode or recurrent depressive disorder,
      paranoid schizophrenia, and schizoaffective disorders) were included in the
      study. The following examinations were carried out in each patient on admission
      and at discharge: (1) the plasma lipid parameters total cholesterol (TC), low
      density lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density
      lipoprotein (HDL), and triglycerides (TRI) were determined, and (2) the
      psychopathological features were recorded employing the AMDP system and the AMDP
      Syndrome Scales. Within the context of a naturalistic clinical setting with a
      choice of psychoactive drugs available, patients were subdivided at the end of
      treatment into eight treatment groups, as follows: group 1, treatment with
      butyrophenones; group 2, treatment with tricyclics; group 3, treatment with
      butyrophenones and tricyclics; group 4, treatment with butyrophenones, tricyclics
      and selective serotonin reuptake inhibitors; group 5, treatment with
      butyrophenones and lithium; group 6, treatment with tricyclics and lithium; group
      7, treatment with butyrophenones, tricyclics and lithium; and group 8, treatment
      with butyrophenones, tricyclics, selective serotonin reuptake inhibitors and
      lithium. To compare the changes in the eight treatment groups, mixed general
      linear models including diagnosis, gender, age, body mass index changes, and
      baseline values were applied using proc GLM of SAS. Butyrophenones induce an
      increase in TC, LDL, and TC/TRI ratio, whereas tricyclics lead to an increase in
      TC, LDL, VLDL, and TRI. In combined medication of butyrophenones and tricyclics
      the effects of tricyclics predominate. Comedication of lithium inhibits the
      increase in TC and LDL induced by butyrophenones and/or tricyclics. Treatment
      groups with lipid changes of the same type (decrease, no change, or increase)
      were combined in "lipid change groups". Analyses of variance or covariance (with
      psychopathological admission value as covariate where there were significant
      differences in psychopathological admission mean values between the groups) of
      these lipid change groups with regard to the changes in the Depressive Syndrome
      Scale and the Hostility Syndrome Scale gave results which are interpreted as
      follows: an increase in TC or LDL inhibits the remission of hostility, whereas an
      increase in TRI with concomitant decrease in TC, or else a relatively greater
      increase in TRI than in TC promotes the remission of hostility. A decrease in TRI
      or VLDL promotes the remission of depression. Our data and findings published in
      the literature may suggest that systemic changes in plasma lipid parameters, at
      the cellular level, induce changes in the fluidity of brain cell membranes. We
      hypothesize that an increase in plasma TC or LDL and/or a decrease in plasma TRI
      or VLDL may induce a relative decrease in brain cell membrane fluidity with
      decreased presynaptic serotonin reuptake and increased postsynaptic serotonin
      function. This proposed increase in brain serotonin function would finally result
      in an anti-depressive, aggression-promoting effect. Conversely, a decrease in
      plasma TC or LDL and/or an increase in plasma TRI or VLDL may induce a relative
      increase in brain cell membrane fluidity with increased presynaptic serotonin
      reuptake and decreased postsynaptic serotonin function. This proposed decrease in
      brain serotonin function would result in an anti-aggressive, depression-promoting
      effect.

PMID- 9562211
TI  - Risperidone-induced tardive dyskinesia.
AB  - This report presents a potential case of risperidone-induced tardive dyskinesia.
      A 28 year old white schizophrenic male has been under risperidone monotherapy for
      about one year when he developed dyskinetic movements. There was only a short
      term exposure to classic antipsychotics prior to risperidone administration.

PMID- 9562212
TI  - Risperidone and tardive dyskinesia in organic psychosis.

PMID- 9562213
TI  - Ultrarapid metabolism of clomipramine in a therapy-resistant depressive patient,
      as confirmed by CYP2 D6 genotyping.

PMID- 9562214
TI  - Effect of carbohydrate supplementation on plasma glutamine during prolonged
      exercise and recovery.
AB  - Muscle glycogen and glucose have been suggested to be carbon-chain precursors for
      glutamine synthesis in skeletal muscle. Therefore, the aim of the present study
      is to investigate whether carbohydrate supplementation affects plasma glutamine
      and other amino acids during exercise and 7 h of recovery. Eight well-trained
      subjects cycled at an alternating workload of 50 and 80% Wmax until exhaustion
      (59 to 140 min). During the exercise bout the subjects received either water
      (control) or a carbohydrate (CHO) drink (83 g CHO x l(-1), 2 ml x kg(-1) per kg
      body weight every 15 min). Plasma glutamine concentration appeared not to be
      affected by exercise, as a significant increase was only observed at some points
      in time during the control test. During recovery, however, plasma glutamine
      concentration decreased from 682+/-24 and 685+/-19 micromol x l(-1) at exhaustion
      to 552+/-19 and 534+/-12 micromol x l(-1) after 2 h of recovery for the control
      and CHO test, respectively. Plasma glutamine concentration returned to pre
      exercise values after 7 h of recovery. Alanine concentration increased during
      exercise in both tests. During the recovery period the concentration of alanine
      (48%), and total amino acids (23%) decreased below the pre-exercise level. The
      plasma alanine and the total amino acid concentration was still suppressed after
      7 h of recovery. In conclusion, carbohydrate supplementation had neither an
      effect during exercise nor during recovery on the concentration of plasma
      glutamine or other amino acids. Exercise, however, causes a substantial decrease
      in the plasma amino acid concentration during recovery.

PMID- 9562215
TI  - Thermal and cardiovascular strain from hypohydration: influence of exercise
      intensity.
AB  - This study determined the effects of exercise intensity on the physiologic
      (thermal and cardiovascular) strain induced from hypohydration during heat
      stress. We hypothesized that the added thermal and cardiovascular strain induced
      by hypohydration would be greater during high intensity than low intensity
      exercise. Nine heat-acclimated men completed a matrix of nine trials: three
      exercise intensities, 25%, 45% and 65% VO2 max; and three hydration levels,
      euhydration and hypohydration at 3% and 5% body weight loss (BWL). During each
      trial, subjects attempted 50 min of treadmill exercise in a hot room (30 degrees
      C db, 50% rh) while body temperatures and cardiac output were measured.
      Hypohydration was achieved by exercise and fluid restriction the day preceding
      the trials. Core temperature increased (P<0.05) 0.12 degrees C per%BWL at each
      hypohydration level and was not affected by exercise intensity. Cardiac output
      was reduced (P<0.05) compared to euhydration levels and was reduced more during
      high compared to low intensity exercise after 5% BWL. It was concluded that: a)
      the thermal penalty (core temperature increase) accompanying hypohydration is not
      altered by exercise intensity; and b) at severe hypohydration levels, the
      cardiovascular penalty (cardiac output reduction) increases with exercise
      intensity.

PMID- 9562216
TI  - Bone mineral density and menstrual irregularities. A comparative study on
      cortical and trabecular bone structures in runners with alleged normal eating
      behavior.
AB  - Bone mineral density (BMD), and associated biochemical and endocrine markers were
      compared in a group of runners with menstrual dysfunction (IR, n=13), and a group
      of performance matched eumenorrheic runners (R, n=15). All subjects claimed to
      have normal eating habits. Body height and weight, body mass index, and amount of
      body fat were similar. The IR group consisted of 5 presently oligomenorrheic (O)
      and 8 presently amenorrheic (A) runners. The BMD values of the athletes were
      additionally compared with corresponding values in a reference group (C) of
      healthy age matched controls (n=54). BMD values were significantly lower in IR
      compared with R on all measuring sites: Total body (-9%, p=0.03), femoral neck (
      11%, p=0.01), lumbar spine (-12%, p=0.001), lower leg (-6.5%, p=0.03) and arms (
      7%, p=0.01). In addition, IR athletes had lower total body (-5%, p=0.01), and
      lumbar spine BMD (-10%, p=0.001) than C. No differences were observed in serum
      IGF-1, SHBG, testosterone and cortisol, or in the biochemical marker of bone
      formation (osteocalcin) and bone resorption (1 CTP). Values of serum E2, FSH and
      LH were low in IR and normal in R. TSH was in the normal range in both groups,
      but f-T4 was significantly lower in IR than in R. The athletes were furthermore
      grouped according to past and present menstrual dysfunction severity. At all
      measuring sites, with the exception of the lower leg, increasing menstrual
      dysfunction severity was linearly associated with declining BMD values (p<0.05).
      In conclusion, even highly conditioned cortical bone tissue seems to be
      negatively related to menstrual disorders, which may serve to explain the high
      incidence of stress fractures in athletes with menstrual disorders. Single
      measurements of biochemical markers of bone resorption and formation may not
      reflect the current bone status.

PMID- 9562217
TI  - Limits to maximal performance in individuals with spinal cord injury.
AB  - The purpose of this study was to examine the effect of four conditions that might
      improve oxygen transport and/or utilization during maximal exercise performance
      in individuals with spinal cord injury (SCI). Five males with tetraplegia (TP)
      and four males with paraplegia (PR) performed maximal arm cranking exercise in
      the following positions: 1) sitting; 2) supine; and 3) sitting with the addition
      of a) anti-gravity suit (anit-G), b) elastic stockings and abdominal binder, and
      c) functional electrical stimulation (FES) of the paralysed leg muscles. Peak
      power output (PO peak), peak oxygen uptake (VO2peak), peak heart rate (HR peak)
      and maximal systolic blood pressure were significantly lower in TP compared to PR
      for all conditions. A significant decrease in HR peak for PR, and a significant
      increase in VO2peak/kg for TP was seen during the supine compared to sitting
      condition. Respiratory exchange ratio (R) decreased significantly during the FES
      compared to the sitting condition in TP. No other changes were observed for any
      of the other conditions in either group. Improvements in central circulation
      previously reported during submaximal exercise for these four conditions did not
      result in a concomitant rise in maximal exercise performance. The results of this
      study suggest that the limitation in VO2peak for individuals with SCI is located
      peripherally (small active muscle mass) rather than centrally (heart or lungs).

PMID- 9562219
TI  - Effect of a nasal dilatator on nasal patency during normal and forced nasal
      breathing.
AB  - A nasal dilatator contains two elastic strips, which provide the dilatator with a
      spring action. The aimed function of the nasal dilatator is to slightly open the
      nares and hereby facilitate nasal breathing. The aim of this study was to
      evaluate the effect of a nasal dilatator by measuring nasal airway resistance
      during normal breathing and nasal forced expiratory and inspiratory flows and
      volumes with and without use of the nasal dilatator. Nasal resistance was
      measured with a whole body plethysmograph; maximal expiratory and inspiratory
      flow-volume curves were obtained with a pneumotachometer. These measurements were
      performed in ten healthy volunteers. No significant difference was found between
      nasal resistance with and without the nasal dilatator. However, values for forced
      inspiratory volume in 1 s (FIV 1) with the nasal dilatator, proved to be
      significantly higher (p=0.045,paired t-test) than values obtained without the
      nasal dilatator; mean improvement was 0.26 L (sd = 0.36). No significant
      improvement in peak inspiratory flow (PIF) was found, as was the case for the
      other flows and volumes. It is concluded that the nasal dilatator causes no
      appreciable improvement of nasal patency during normal breathing. In view of the
      fact that FIV 1 values increased significantly, we believe that the nasal
      dilatator prevents collapse of the external nares during forced inspiration. A
      beneficial effect during exercise when ventilation is increased is however
      doubtful because in that situation most volunteers switch to oronasal breathing
      already at submaximal exercise.

PMID- 9562218
TI  - The relationship between serum oestradiol concentration and energy balance in
      young women distance runners.
AB  - Reproductive dysfunction in women distance runners has been linked to an
      imbalance between energy intake (EI) and energy expenditure (EE) which leads to
      an energy deficit. To determine whether ovarian suppression is associated with an
      energy deficit, the relationships between serum oestradiol (E2) concentration and
      indices of energy balance (EB) were explored in a group of women runners with a
      variety of menstrual patterns and a range of activity levels. Subjects comprised
      33 women distance runners of mean (SD) age 27.2 (1.8) years. Sixteen of these
      women were defined as eumenorrhoeic (11-13 menstrual bleeds per year during the
      past 2 years), 8 as oligomenorrhoeic (< or = 3 menstrual bleeds per year for 2
      years) and 9 as amenorrhoeic (absence of menses for > 1 year). Their volume of
      running training ranged from 36 to 97 km x wk(-1) [mean (SD): 68.6 (21.4) km x
      wk(-1). The body mass index (BMI) and percent body fat (BF) of each subject was
      measured. Their mean daily energy balance (EB) was calculated by subtracting
      their dietary EI from their estimated EE recorded over 7 days. Serum
      concentrations of E2, total T3 and IGF-1 were measured from a fasting blood
      sample (taken in early follicular phase for Eu women). Relationships between
      serum E2, T3 and IGF-1, EB, BMI and BF were explored using bivariate correlation
      and regression analysis. The results showed that the most powerful predictors of
      serum E2 concentration were estimated EB (r = 0.88, P<0.001), serum T3 (r=0.94,
      P<0.001) and IGF-1 (r=0.84; P<0.001). Weaker correlations were observed between
      serum E2 and BMI (r=0.42; P=0.008) and serum E2 and BF (r=0.48; P=0.004). These
      relationships add support to the hypothesis that reproductive dysfunction in
      women distance runners is associated with an energy deficit.

PMID- 9562220
TI  - Ergometric and psychological findings during overtraining: a long-term follow-up
      study in endurance athletes.
AB  - In the present prospective longitudinal study 17 male endurance trained athletes
      (cyclists and triathletes; age 23.4+/-6.7 years, VO2max 61.2+/-7.5 ml x min(-1) x
      kg(-1); means+/-SD) were investigated both during a state of overtraining
      syndrome (OT: N=15), mainly induced by an increase of exercise intensity, as well
      as several times in a state of regular physical ability (NS: N=62). Cycle
      ergometric and psychological data were compared for a period of approximately 19
      months. On 2 separate days, each subject performed a maximum incremental graded
      exercise, two anaerobic tests (10 s and 30 s) as well as a short-endurance
      "stress test" with the intensity of 110% of the individual anaerobic threshold
      until volitional exhaustion. The mood state was recorded by a psychological
      questionnaire including 40 basic items. During OT the submaximal lactate
      concentrations were slightly decreased. The performance of the 10 s- and 30 s
      tests was unaffected. In contrast, the duration of the "stress test" decreased
      significantly by approximately 27% during OT compared to the individual NS. The
      submaximal oxygen uptake measured during the incremental graded exercise was
      slightly higher during OT as compared to NS, whereas the submaximal and maximal
      respiratory exchange ratio, maximal heart rate and maximal lactate concentrations
      were decreased. At the 10th minute of the "stress test", ammonia tended to be
      increased during OT (P=0.048). The parameters of mood state at rest as well as
      the subjective rating of perceived exertion during exercise were significantly
      impaired during OT. In conclusion, the results indicate a decreased intramuscular
      utilization of carbohydrates with diminished maximal anaerobic lactacid energy
      supply during OT. Neither the lactate-performance relationship during incremental
      graded exercise nor the anaerobic alactacid performance showed alterations. The
      duration of the short-endurance "stress test", the maximal lactate concentration
      of the incremental graded exercise as well as the altered mood profile turned out
      to be the most sensitive parameters for the diagnosis of OT.

PMID- 9562221
TI  - The effect of training and epinephrine infusion on ratings of perceived exertion
      (RPE).
AB  - Seven untrained males (mean age [+/-SD] = 25.6+/-3.9 yr, mean ht = 177.0+/-5.9
      cm, mean wt = 65.8+/-7.4 kg) completed a 6-week exercise program (cycle
      ergometer). Prior to training, and at the end of each week of training, each
      subject performed a 20 min constant-power exercise test (absolute power was the
      same each week). At the end of the six week training program (within a few days),
      an additional 20 min constant-power test was performed, during which epinephrine
      was infused at a rate of 100 ng x kg(-1) x min(-1) over the final 10 min of
      exercise. Training significantly (P<0.05) reduced end-exercise ratings of
      perceived exertion (RPE), plasma epinephrine concentration [Epi], plasma
      norepinephrine concentration [NE], blood lactate concentration [La-], minute
      ventilation (V(E)), heart rate (HR), and blood glucose concentration [Glc].
      Epinephrine infusion failed to increase RPE despite significant (p < 0.05)
      increases in [Epi], [La-], V(E) and [Glc]. Therefore, the present data indicate
      that RPE during exercise is not causally related to changes in plasma [Epi]. It
      also appears that modest changes in plasma [NE], blood [La-], V(E) and blood
      [Glc] during constant-power cycle ergometry (as observed during Epi infusion) do
      not impact RPE.

PMID- 9562222
TI  - The critical power function is dependent on the duration of the predictive
      exercise tests chosen.
AB  - The linear relationship between work accomplished (W(lim)) and time to exhaustion
      (t(lim)) can be described by the equation: W(lim) = a + CP x t(lim). Critical
      power (CP) is the slope of this line and is thought to represent a maximum rate
      of ATP synthesis without exhaustion, presumably an inherent characteristic of the
      aerobic energy system. The present investigation determined whether the choice of
      predictive tests would elicit significant differences in the estimated CP. Ten
      female physical education students completed, in random order and on consecutive
      days, five all-out predictive tests at preselected constant-power outputs.
      Predictive tests were performed on an electrically-braked cycle ergometer and
      power loadings were individually chosen so as to induce fatigue within
      approximately 1-10 mins. CP was derived by fitting the linear W(lim)-t(lim)
      regression and calculated three ways: 1) using the first, third and fifth W(lim)
      t(lim) coordinates (I135), 2) using coordinates from the three highest power
      outputs (I123; mean t(lim) = 68-193 s) and 3) using coordinates from the lowest
      power outputs (I345; mean t(lim) = 193-485 s). Repeated measures ANOVA revealed
      that CPI123 (201.0+/-37.9W) > CPI135 (176.1+/-27.6W) > CPI345 (164.0+/-22.8W)
      (P<0.05). When the three sets of data were used to fit the hyperbolic Power
      t(lim) regression, statistically significant differences between each CP were
      also found (P<0.05). The shorter the predictive trials, the greater the slope of
      the W(lim)-t(lim) regression; possibly because of the greater influence of
      'aerobic inertia' on these trials. This may explain why CP has failed to
      represent a maximal, sustainable work rate. The present findings suggest that if
      CP is to represent the highest power output that an individual can maintain "for
      a very long time without fatigue" then CP should be calculated over a range of
      predictive tests in which the influence of aerobic inertia is minimised.

PMID- 9562223
TI  - Stress hormones and the immunological responses to heat and exercise.
AB  - This review focuses on the response of "stress" hormones to heat, exercise
      (single or repeated bouts), and combinations of these stimuli, with particular
      reference to their impact upon immune function. Very hot conditions induce a
      typical stress response, with secretion of catecholamines and cortisol. The
      catecholamines induce a demargination of leukocytes, and cortisol subsequently
      causes cells to migrate to lymphoid tissue. Sustained exercise, even in a
      thermally comfortable environment, induces a larger hormonal response than
      moderate thermal stress. With moderate exercise, increases in leukocyte numbers
      are related mainly to plasma norepinephrine concentrations, but with more intense
      exercise epinephrine concentrations assume a major importance. As exercise
      continues, plasma cortisol levels also rise, inducing an influx of neutrophils
      from bone marrow and an efflux of other leukocyte subsets. A combination of
      exercise and heat stress augments both hormonal and leukocyte responses. But
      these changes seem to be reversed if temperatures are clamped by exercising in
      cold water. If a second bout of exercise is performed with an inter-test interval
      of 30-45 min, neither hormone concentrations nor immune responses show any great
      cumulative effect under temperate conditions. However, in a hot environment the
      second exercise bout induces a larger and more persistent neutrophilia. Training
      influences these various responses mainly by decreasing the stress imposed when
      exercising at a given absolute work-rate.

PMID- 9562224
TI  - Collagen crosslinks in chondromalacia of the patella.
AB  - The aim of the study was to determine collagen concentration and collagen
      crosslinks in cartilage samples from chondromalacia of the patella. To study the
      extracellular matrix alterations associated to chondromalacia, we determined the
      concentration of collagen (hydroxyproline) and its hydroxylysylpyridinoline and
      lysylpyridinoline crosslinks from chondromalacia foci of the patellae in 12
      patients and 7 controls from apparently normal cadavers. The structure of the
      collagen network in 8 samples of grades II-IV chondromalacia was examined under
      polarized light microscopy. The full-thickness cartilage samples taken with a
      surgical knife from chondromalacia lesions did not show changes in collagen,
      hydroxylysylpyridinoline and lysylpyridinoline concentration as compared with the
      controls. Polarized light microscopy showed decreased birefringence in the
      superficial cartilage of chondromalacia lesions, indicating disorganization or
      disappearance of collagen fibers in this zone. It is concluded that the collagen
      network shows gradual disorganization with the severity of chondromalacia lesion
      of the patella without changes in the concentration or crosslinks of collagen.

PMID- 9562225
TI  - Effect of long-term intensive endurance training on left ventricular structure
      and diastolic function in prepubertal children.
AB  - In children, the fact that cardiac anatomy and function, particularly during the
      diastolic phase, can adapt to endurance training is still uncertain. Therefore,
      this study was undertaken to evaluate the effect of a long-term intensive
      endurance swimming program on the cardiac structure and function of 10-11 year
      old children. The population consisted of 9 children who belonged to a local
      youth swimming team (S) and 11 recruited from a primary school to serve as a
      control group (C). The swimmers had been training on average 10 to 12 h x wk(-1)
      for at least 2 years. All the subjects were examined by M-mode, 2-dimensional and
      pulsed-wave Doppler analyses according to standard procedures recommended by the
      American Society of Echocardiography. Investigations were carried out at rest
      with the subjects in a supine position. The results showed that highly trained
      children exhibited significantly higher left ventricular (LV) internal diameter
      (S: 41.6+/-1.6, C: 39.0+/-2.2 mm/m(1/3) surface area, p<0.01) and LV mass (S:
      68+/-7, C: 59+/-5 g/m2 SA, p<0.01). There were, however, no differences between S
      and C for chamber wall thickness (posterior wall S: 5.2+/-0.6, C: 5.3+/-0.6
      mm/m(1/3) SA; septum S: 5.8+/-0.3, C: 5.8+/-0.4 mm/m(1/3) SA), LV systolic
      function parameters (ejection fraction S: 77.1+/-0.3, C: 77.7+/-0.4%; shortening
      fraction S: 38.9+/-3.0, C: 39.7+/-4.1%) and the diastolic function parameters,
      estimated from LV inflow velocitometry (E wave S: 1.04+/-0.12, C: 1.07+/-0.16
      m/s; A wave S: 0.45+/-0.10, C: 0.55+/-0.11 m/s). Finally, transaortic Doppler
      examinations demonstrated similar resting cardiac output (Qc) between both groups
      (S: 3.76+/-0.81, C: 3.90+/-0.67 l x min(-1)). However, Qc were obtained with
      significantly lower heart rates (S: 69+/-7, C: 83+/-14 beat x min(-1), P<0.01)
      and higher stroke volumes (S: 55.2+/-8.0, C: 47.5+/-8.5 ml, P<0.05) in S when
      compared to C. Thus, these findings strongly suggest that, as has been shown
      before in adults, several cardiac adaptations (including resting bradycardia,
      increased stroke volume and enlarged left ventricular internal dimensions) can
      occur in prepubertal children as a result of intensive endurance training.
      However, our results did not demonstrate any effects of such training during
      prepuberty on both diastolic and systolic functions parameters.

PMID- 9562226
TI  - Asthma management: the challenge of equivalence.
AB  - Increasing prevalence and severity of asthma worldwide encourage the development
      of new antiasthmatic drugs, alternative treatment regimens and improved
      formulations of established drugs. Whereas the efficacy of new chemical entities
      (NCEs) is usually demonstrated by superiority over placebo or a subtherapeutic
      dose of the active drug, equivalence concepts have to be used in the following
      situations: the need to replace chlorofluorocarbon (CFC) propellants for
      inhalative asthma medications by suitable alternatives, and the need to
      demonstrate that an alternative treatment regimen is not clinically inferior to
      an established reference treatment. To cover both situations, the recent ICH
      guidance on biostatistics clearly distinguishes between two-sided equivalence
      trials and one-sided non-inferiority trials. In this context, non-inferiority
      always means "not inferior by a clinically relevant amount". After having
      confirmed non-inferiority, superiority of the alternative test treatment over the
      reference treatment can additionally be tested without the need to adjust the
      significance level. The definition of equivalence acceptance limits becomes
      crucial, particularly in studies conducted in the flat range of the dose-response
      curve of inhaled steroids. In order to assess the non-inferiority of steroid
      sparing add-on treatments we propose a one-sided test based on post-/pre-ratios
      which have substantially reduced coefficients of variation compared to the post
      treatment values themselves. The non-inferiority acceptance limit of 0.90 - as
      opposed to 0.80 in bioequivalence assessment - reflects clinically irrelevant
      changes of lung function variables. The proposed methodology is illustrated by 2
      examples from randomized, double-blind, parallel-group studies comparing inhaled
      steroid plus theophylline versus doubling the steroid dose in asthmatics who are
      symptomatic on low-dose inhaled steroid.

PMID- 9562228
TI  - Relative bioavailability of rapidly dispersing, plain, and microencapsuled
      acetylsalicylic acid tablets after single dose administration.
AB  - Extent and rate of absorption of acetylsalicylic acid (ASA) from rapidly
      dispersing (Acesal Extra) and plain tablets (Acesal) relative to reference 1
      (plain tablets, Aspirin) and from microcapsuled tablets (Micristin) relative to
      comparable listed tablets (reference 2, Colfarit) were assessed in 2 single-dose
      (0.5 g ASA), open, randomized, crossover studies with intervals of 14 days
      between 2 periods. Both studies were performed in 24 male and female healthy
      volunteers each (age 18-32 years, body weight 48-90 kg, body height 161-190 cm).
      ASA and its metabolite salicylic acid (SA) were measured with an HPLC method
      validated for ASA between 0.2 and 20 microg/ml and for SA between 0.4 and 40
      microg/ml. The test tablets were considered bioequivalent with reference in
      extent of absorption if the 90% confidence limits of the AUC0 to infinity ratio
      were within the range of 0.80-1.25, and in rate of absorption if the confidence
      limits of the Cmax/AUC0 to infinity ratios were within 0.70-1.43. RESULTS:
      Geometric means and 90% confidence limits for the test/reference ratios of the
      comparisons Acesal vs reference 1, Acesal Extra vs reference 1 and Micristin vs
      reference 2 were 1.05 (0.97-1.13), 1.13 (1.05-1.22), 1.02 (0.92-1.14) for ASA
      AUC0 to infinity and 1.02 (0.96-1.07), 1.05 (0.99-1.11), 0.98 (0.91-1.04) for SA
      AUC0 to infinity, respectively. The results for Cmax/AUC of ASA were 1.16 (1.00
      1.34), 1.72 (1.49-1.99), 0.83 (0.73-0.94) and of SA 1.02 (0.98-1.07), 1.07 (1.02
      1.12), 0.93 (0.88-0.97). CONCLUSION: Acesal and Micristin were bioequivalent with
      the respective references in both extent and rate of absorption. Acesal Extra and
      reference 1 were bioequivalent with regard to extent only. Acesal Extra was
      absorbed faster.

PMID- 9562227
TI  - Grapefruit juice increases oral nimodipine bioavailability.
AB  - The bioavailability of dihydropyridine calcium channel blockers following oral
      administration was shown to be increased by concomitant intake of grapefruit
      juice for all drugs of this class tested up to now. Here we report a randomized
      crossover interaction study on the effects of grapefruit juice on the
      pharmacokinetics of nimodipine and its metabolites. Eight healthy young men (4
      smokers/4 nonsmokers) were included. Nimodipine was given as a single 30 mg
      tablet (Nimotop) with either 250 ml of water or 250 ml of grapefruit juice (751
      mg naringin/l). Drug concentrations in plasma withdrawn up to 24 hours postdose
      were measured by GC-ECD, and model-independent pharmacokinetic parameters were
      estimated. The study was handled as an equivalence problem. Point estimators and
      ANOVA based 90% confidence intervals (CI) were calculated for the test (=
      grapefruit juice period) to reference (= water period) ratios using dose
      normalized concentrations. The absence of a relevant interaction was assumed if
      the CIs were within the 0.67-1.50 range. Cmax for nimodipine reached 124% of the
      reference period (90% CI 0.76-2.01), AUC was increased to 151% (90% CI 114%
      200%), respectively. The null hypothesis "relevant interaction" thus could not be
      rejected for the primary pharmacokinetic parameters AUC and Cmax. The ratios of
      metabolite AUC to parent drug AUC were slightly reduced with grapefruit juice
      intake. Additionally, there was evidence for a more pronounced hemodynamic
      response in the grapefruit juice period. To avoid the interaction, nimodipine
      should not be taken with grapefruit juice.

PMID- 9562229
TI  - A comparative study of pharmacodynamics and bioavailability of 2 different
      desmopressin nasal sprays.
AB  - The antidiuretic effect and pharmacokinetics were investigated in 16 healthy,
      male overhydrated volunteers after intranasal administration of 20 microg
      desmopressin. The antidiuretic activity was measured by determination of urine
      osmolality and diuresis every 15 minutes over a period of 8 hours. Both study
      preparations were equally effective regarding a rapid onset of activity and a
      highly reproducible magnitude of effect. Urine osmolalities, analyzed as area
      under the time curve (AUCosm) and maximum urine osmolalities were similar for
      both nasal sprays. Urine volume, analyzed as area under the time curve, was
      raised after treatment with the test preparation. Bioequivalence was assessed for
      the primary criterion AUCosm by a calculated mean ratio (test/reference) of
      102.8% and a 90% confidence interval ranging from 95.4% to 110.8%. Plasma levels
      of desmopressin, measured by a specific and sensitive radio-immunoassay method,
      were already detectable 20 minutes after administration. The mean time curves
      were parallel at different concentration levels. The maximum desmopressin plasma
      concentrations of both preparations were comparable, showing high interindividual
      variability. The times of reaching maximum plasma concentrations were similar.
      Desmopressin bioavailability was increased after treatment with the test
      preparation (mean ratio of 130.8% and a 90% confidence interval ranging from
      109.9% to 155.7%). Both preparations showed a pronounced biological effect with
      similarly raised urine osmolalities. The detected differences in bioavailability
      seem to have no direct correlation to the biological response.

PMID- 9562230
TI  - Lack of CYP3A inhibition effects of sertindole on terfenadine in healthy
      volunteers.
AB  - The effect of sertindole (a new selective antipsychotic compound) on the
      pharmacokinetic disposition of terfenadine was investigated. Thirteen subjects
      who completed the study received a single 120 mg dose of terfenadine alone or
      with concomitant 20 mg sertindole daily. The mean values for terfenadine Cmax
      (alone: 2.42 +/- 1.48 ng/ml, in combination: 2.99 +/- 1.85 ng/ml) and AUC (29.6
      +/- 18.9 vs 37.9 +/- 23.4 ng x hr/ml) did not change statistically significant in
      the presence of sertindole (p > 0.05). Similarly, the mean Cmax (531 +/- 195 vs
      506 +/- 190 ng/ml) and AUC (3,728 +/- 1,163 vs 4,003 +/- 1,739 ng x hr/ml) values
      of carboxyterfenadine did not change statistically significant in the presence of
      sertindole (p > 0.05). The other pharmacokinetic parameters of terfenadine and
      carboxyterfenadine such as Tmax, t1/2, as well as the carboxyterfenadine to
      terfenadine Cmax and AUC ratios did not change in the presence of sertindole.
      Although terfenadine is a substrate for CYP3A (cytochrome P-450 3A), while
      sertindole is a substrate for both CYP2D6 and CYP3A4, the results in this study
      suggest that sertindole, at a clinical dose, is not an inhibitor of the
      metabolism of terfenadine.

PMID- 9562231
TI  - Nephrotoxic potential of antiinfective drugs as assessed by tissue-specific
      proteinuria of renal antigens.
AB  - In order to assess the nephrotoxic potential of antibiotics, various
      aminoglycosides and cephalosporins were tested for their potency to alter the
      excretion of tubular marker proteins (and brush border antigens) or to change the
      normal pattern of serumproteinuria as analyzed by SDS polyacrylamidgel gradient
      electrophoresis. After aminoglycosides, especially after gentamicin injection, a
      cumulative highly significant increase in the urinary output of marker proteins
      emerged (healthy volunteer model). In contrast, cephalosporins exhibited
      practically no nephrotoxic effect on proximal tubule cells. Excretion of tubular
      marker proteins was enhanced under combined administration of cephalosporins and
      aminoglycosides mainly due to the aminoglycoside component. There was no
      nephrotoxic synergy of both drugs. Image analysis of rat kidney sections after
      injection of aminoglycosides revealed that increased shedding of tubular membrane
      components under the toxic challenge is followed by rapid inductive repair
      processes (overshoot protein synthesis) of tubular cells. After a limited acute
      toxic damage tubular cells may recover within one week.

PMID- 9562232
TI  - Pharmacokinetics of mycophenolate mofetil in renal transplant recipients on
      peritoneal dialysis.
AB  - Little is known about the pharmacokinetics of mycophenolatic acid (MPA) in the
      early posttransplant period after renal transplantation. We studied the impact of
      peritoneal dialysis on the pharmacokinetics of MPA in 5 patients following renal
      transplantation (3-6 weeks after transplantation). Three patients had a
      glomerular filtration rate (GFR) of less than 10 ml/min, 1 patient had a GFR of
      32, and 1 of 58 ml/min. Pharmacokinetics of MPA and its main metabolite
      mycophenolic acid glucuronide (MPAG) were studied on 2 consecutive days (12-hour
      intervals: with and without peritoneal dialysis). Dosing of MPA was 2 x 1 g/day.
      MPA and MPAG concentrations were determined by HPLC methods. After initiation of
      peritoneal dialysis in patients with severe renal impairment (GFR < 10 ml/min)
      MPA area under the concentration curve (AUC) decreased substantially (15-59%).
      The calculated clearance of MPA was higher (14.6 vs 8.1 ml/min/kg) on the day of
      peritoneal dialysis than during the dwell-free day. MPAG-AUC decreased up to 26%
      in these patients. In both patients with a GFR > 30 ml/min we observed an
      increase of MPA-AUC on the day of peritoneal dialysis and a decreased MPA
      clearance. MPAG-AUCs remained stable. Patients with a reduced GFR had much higher
      MPAG values than patients with a GFR 30 ml/l, however, we did not observe any
      differences for the MPA levels. We found a significant inverse correlation
      between GFR and MPAG-AUC (r = 0.91, p < 0.05). While MPA was found only in traces
      in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by
      peritoneal dialysis reached up to 2 g per 12 hours, representing up to 1.2 g of
      MPA. This is the first report describing a reduction of MPA- and MPAG-AUC during
      peritoneal dialysis. Further studies are needed to better understand the
      pharmacokinetics of mycophenolat mofetil during peritoneal dialysis.

PMID- 9562233
TI  - Nephrotoxicity of antiinfective drugs.
AB  - Antiinfective drugs may show the same mechanisms of nephrotoxicity as other
      drugs, and these can be subgrouped into vascular, tubulotoxic, tubulo
      obstructive, and immunologic effects. While vascular effects of antiinfective
      drugs are rare, tubulotoxicity is a well known phenomenon, especially in
      connection with aminoglycosides and amphotericin B as well as cephalosporins,
      pentamidine, foscarnet, and cidovir. The tubulo-obstructive effect caused by
      precipitation of the drug and first observed after treatment with sulfonamides in
      the 1940s, has become a renascent problem now that high doses of sulfonamides are
      being given to immunocompromised patients (sulfadiazine, cotrimoxazole).
      Moreover, this effect has also been associated with newer antiviral drugs like
      acyclovir and indinavir. We describe a transplant patient who received high doses
      of cotrimoxazole for pneumocystis carinii pneumonia and lost transplant function
      mainly due to bioptically proven glomerular and tubular crystallization with
      tubular degeneration caused by sulfamethoxazole. Acute interstitial nephritis is
      the main immunologic effect of antiinfective drugs (especially rifampicin but
      also cephalosporins, quinolones, sulfonamides, and penicillins). Immune
      stimulation by cytokine treatment (mainly interferon-alpha) involves several
      kinds of autoimmune renal diseases like acute interstitial nephritis or
      glomerulonephritis as well as interstitial and vascular rejection of renal
      transplants.

PMID- 9562234
TI  - Relationship between pharmacokinetic half-life and pharmacodynamic half-life in
      effect-time modeling.
AB  - A pharmacodynamic parameter relating time-dependent changes of the effect with
      time-dependent changes of concentrations has yet to be developed. In
      pharmacokinetics, half-lives (T1/2kin) are used to describe the relation between
      concentration (C) and time (t). In pharmacodynamics, often the sigmoid Emax model
      and the Hill equation are used (E = Emax CH/(EC50H + CH)) to describe the
      relation between effect (E) and concentration (C). To describe the correlation
      between effect (E) and time (t), a pharmacodynamic half-life (T1/2dyn) could be
      estimated if the use of the term half-life is not restricted only to log-linear
      first order processes. To bisect the drug effect a variable time (t1-2 = t2-t1)
      will be required for this nonlinear process. The bisection of the effect (E2 =
      1/2 E1) is associated with a decrease in concentrations (C2 = C1 exp(-0.693 t1
      2/T1/2kin)). A mathematical relationship can be derived between pharmacodynamic
      half-life (T1/2dyn = t1-2) and pharmacokinetic half-life (T1/2dyn = T1/2kin (ln
      (1 + ln(a)/ln(2))/H ) with (a = (EC50H + C1H)/(EC50H + C2H)). For concentrations
      in the range of the EC50 value with the Hill coefficient (H = 1), the
      pharmacodynamic half-life will be 1.6-2.0 times the kinetic half-life (T1/2dyn <
      or = 2.0 T1/2kin). For high concentrations (C1 > EC50), the dynamic half-life
      will grow much longer than the kinetic half-life, consequently the effect of a
      drug will not increase but it will last longer. The pharmacodynamic half-life
      turns out to be a specific estimate for the effect time relation, being a
      concentration-dependent function of the kinetic half-life.

PMID- 9562235
TI  - Drug utilization in Europe--report of the EURO-DURG workshop and joint symposium
      with the EACPT Berlin 16.9-18.9 1997. European Drug Utilization Research Group.
      European Association for Clinical Pharmacology and Therapeutics.
AB  - Around 1,000 participants from all European countries, but also from overseas,
      visited the Second International Congress of the European Association for
      Clinical Pharmacology and Therapeutics (EACPT) in Berlin. The EACPT appreciates
      the cooperation with other scientific organizations. Five out of 19 symposia
      offered could be presented jointly with other European societies. One of the
      symposia took place in conjunction with the European Drug Utilization Research
      Group (EURO-DURG). The main topic of this joint symposium, led by Professor Ulf
      Bergman (Huddinge, Sweden) and Dr. Liselotte von Ferber (Cologne, Germany), was
      the use of drugs and its determinants "in real life" compared to its use under
      conditions of clinical research. The poster exhibition of this symposium included
      80 posters. Attended by 110 participants from 25 countries, the EURO-DURG
      workshop took place at the very beginning of the joint symposium.

PMID- 9562236
TI  - Role of aldehydes in fructose induced hypertension.
AB  - Aldehydes are formed in tissues of humans and animals as intermediates of glucose
      and fructose metabolism and due to lipid peroxidation. N-acetyl cysteine (NAC),
      an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing
      their damaging effect on physiological proteins. We measured systolic blood
      pressure (SBP), platelet cytosolic free calcium [Ca2+]i and tissue aldehyde
      conjugates in fructose induced hypertensive Wistar-Kyoto (WKY) rats and examined
      the effect of NAC in the diet on these parameters. Animals age 7 weeks were
      divided into three groups of 6 animals each and were treated as follows: WKY
      control (chow diet and normal drinking water); WKY-Fructose (chow diet and 4%
      fructose in drinking water); WKY-Fructose+NAC (1.5% NAC in chow diet and 4%
      fructose in drinking water). After 11 weeks, systolic blood pressure, platelet
      [Ca2+]i and kidney aldehyde conjugates were all significantly higher in fructose
      treated rats. NAC treatment prevented these changes. These results suggest that
      aldehydes may be the cause of fructose induced hypertension and elevated
      cytosolic free calcium.

PMID- 9562237
TI  - A nucleotide-binding domain of porcine liver annexin VI. Proteolysis of annexin
      VI labelled with 8-azido-ATP, purification by affinity chromatography on ATP
      agarose, and fluorescence studies.
AB  - Porcine liver annexin VI (AnxVI) of Mr 68.000 is an ATP-binding protein as
      evidenced by specific and saturable UV-dependent labelling with 8-azido-[gamma
      32P]ATP or the fluorescent analog of ATP, 2'-(or 3')-O-(2,4,6
      trinitrophenyl)adenosine triphosphate and by binding of AnxVI to ATP-agarose.
      These characteristics of purified AnxVI were used to identify and characterize
      preliminary nucleotide-binding domain of the protein. AnxVI labelled with 8-azido
      ATP was subjected to limited proteolysis and the proteolytic fragments of AnxVI
      that retained the covalently-bound nucleotide were separated by means of gel
      electrophoresis and visualized by exposure of the gel to a phosphor storage
      screen. It was found that the AnxVI proteolytic fragments of Mr 34-36.000 and
      smaller retained the nucleotide. In a reciprocal experiment, AnxVI was digested
      with proteolytic enzymes and in an ATP eluate from an ATP-agarose column protein
      fragments of similar Mr to these labelled with 8-azido-ATP were identified. The
      extent of AnxVI labelling with 8-azido-ATP and the distribution of proteolytic
      fragments varied upon calcium concentration. These results lead to the conclusion
      that there is a nucleotide-binding domain within the AnxVI molecule that is
      functionally similar to the nucleotide-binding domains of other nucleotide
      binding proteins. The nucleotide-binding domain is located close to the
      tryptophan residue 343 of AnxVI and in close vicinity to the Ca2+- and
      phospholipid-binding sites of the protein. This is confirmed by the observation
      that the tryptophan fluorescence intensity of AnxVI decreases in the presence of
      a fluorescence analog of ATP in a calcium-dependent manner, due to the quenching
      properties of the nucleotide and/or fluorescence energy transfer from AnxVI
      tryptophan to fluorophore. Both processes were modulated by the presence of
      phospholipid molecules.

PMID- 9562238
TI  - Identification and characterization of a novel synthetic cannabinoid CP 55,940
      binder in rat brain cytosol.
AB  - We have detected the presence of a specific [3H] CP 55,940 binder in the cytosol
      of rat cerebral cortex. Competition studies showed that only cold CP 55,940 and
      to a lesser extent delta9THC was able to compete with [3H] CP 55,940; little
      competition was observed with either delta8THC or anandamide. Scatchard analysis
      of the data indicate the presence of two distinct binding components having
      affinity constants (Kd) of 0.97 +/- 0.03 nM, 5.83 +/- 0.08 nM, and Bmax of 3.31
      +/- 0.06 pmol/mg protein, 22.2 +/- 1.2 pmol/mg protein respectively. The
      cytosolic CP 55,940 binder was heat stable up to 30 degrees C. Besides the brain
      cytosol, lesser amounts of binding were also detected in the spleen, and testis.
      Liver, kidney and muscle cytosol preparations were found to be devoid of this
      binder. Unlike the previously characterized brain membrane cannabinoid receptor,
      this binder was found to be salt, sulfhydryl blocking reagents and nucleotide
      resistant. Interestingly, dithiothreitol (DTT), a protein-disulfide group
      reducing agent, inhibited the binding of [3H] CP-55,940 to the receptor and
      approximately 80% binding inhibition was obtained at a 5 mM concentration.
      Western blot analysis using anti-receptor antibody reveal the presence of a 95
      110, 50 and 38 kDa band in the brain, spleen and testis cytosolic preparations.
      In conclusion, we have identified the presence of a novel CP 55,940 binder in rat
      cerebral cortex cytosol possessing biochemical properties distinct from those
      previously observed using rat cerebral cortex membrane cannabinoid receptor.

PMID- 9562239
TI  - cDNA cloning and sequencing of Ca2+/calmodulin-dependent protein kinase IIalpha
      subunit and its mRNA expression in diisopropyl phosphorofluoridate (DFP)-treated
      hen central nervous system.
AB  - Diisopropyl phosphorofluoridate (DFP) produces delayed neurotoxicity, known as
      organophosphorus ester-induced delayed neurotoxicity (OPIDN), in hen, human, and
      other sensitive species. A single dose of DFP (1.7 mg/kg, se.) produces first
      mild ataxia followed by paralysis in 7-14 days in hens. DFP treatment also
      increases in vitro autophosphorylation of Ca2+ calmodulin-dependent protein
      kinase II (CaM kinase II) and the phosphorylation of several cytoskeletal
      proteins in the hen brain. To investigate whether increase in CaM kinase II
      activity is associated with increased expression of its mRNA, we cloned and
      sequenced CaM kinase II alpha subunit cDNA, and used it to study CaM kinase II
      expression in brain regions and spinal cord. Hen CaM kinase II alpha subunit
      differs in 7 amino acids from that of rat CaM kinase II. Its mRNA occurs
      predominantly as a 6.7 kb message, which is very close to that of human CaM
      kinase II alpha subunit. Northern blot analysis showed a transient increase in
      CaM kinase II alpha subunit mRNA in the cerebellum and spinal cord of DFP-treated
      chickens. The increase in CaM kinase II mRNA expression is consistent with the
      previously reported increase in its activity in brain and spinal cord, and its
      increased expression only in cerebellum and spinal cord, which are sensitive to
      the Wallerian-type degeneration characteristic of OPIDN, suggests the probable
      role of this enzyme in delayed neurotoxicity.

PMID- 9562240
TI  - An accessory role for ceramide in interleukin-1beta induced prostaglandin
      synthesis.
AB  - Interleukin-1beta (IL-1) is a potent inducer of prostaglandin E2 (PGE2)
      synthesis. We previously showed that ceramide accumulates in fibroblasts treated
      with IL-1 and that it enhances IL-1-induced PGE2 production. The present study
      was undertaken to determine the mechanism(s) by which ceramide and IL-1 interact
      to enhance PGE2 production by examining their respective effects on the rate
      limiting enzymes in PGE2 synthesis, cyclooxygenase-1 (COX-1), cyclooxygenase-2
      (COX-2), and cytosolic phospholipase A2 (cPLA2). IL-1-induced PGE2 synthesis
      required approximately 8 h even though COX-1 was constitutively expressed (both
      mRNA and protein) and enzymatically active in untreated cells. Conversely, COX-2
      mRNA was barely detectable in untreated cells but within 2 h, ceramide or IL-1
      alone induced a 5 and 20 fold increase in COX-2 mRNA, respectively. However, IL-1
      induced COX-2 protein synthesis was only detectable 6-7 h after maximal COX-2
      mRNA induction; COX-2 protein accumulation was not induced by ceramide alone.
      Ceramide however, reduced the length of time required for IL-1 to induce COX-2
      protein accumulation and increased COX-2 protein accumulation. IL-1 induced a 15
      fold increase in COX-1 mRNA including an alternatively spliced form of COX-1. IL
      1, but not ceramide induced cPLA2 mRNA and protein expression which corresponded
      with the initiation of PGE2 synthesis. These observations indicate that, (1)
      while either ceramide or IL-1 rapidly induced COX-2 mRNA, COX-2 protein only
      accumulated in IL-1 treated cells after a delay of 6-7 h, (2) IL-1-induced PGE2
      synthesis required both COX-2 and cPLA2 protein synthesis and, (3) ceramide
      enhanced (temporally and quantitatively) IL-1-induced COX-2 protein

PMID- 9562241
TI  - Sequence of a Menkes-type Cu-transporting ATPase from rat C6 glioma cells:
      comparison of the rat protein with other mammalian Cu-transporting ATPases.
AB  - Rat Atp7a occupied a single open reading frame (274502) which coded for a protein
      of 1492 residues. Rat Atp7a was 98% and 95% identical to published sequences for
      the mouse and Chinese hamster, respectively, and 94% homologous to human ATP7A.
      Compared to ATP7A, the rat transcript coded for an additional alanine (A446) in
      the heavy metal binding (Hmb) domain and showed a 34 bp gap in the 3' UTR. Based
      on published sequence data, hydropathic profiles for rat, mouse, Chinese hamster,
      and human Cu-ATPases were practically identical with the exception of 8
      additional amino acid residues between the 4th and 5th Hmb sites in the human. As
      deduced from amino acid sequence data, Hmb was predicted to have regions with
      helical and beta structures. All four species had five of the six metal binding
      sites centered within hydrophobic regions. The comparative analyses suggested
      that the Hmb region of the molecule could experience numerous amino acid
      substitutions with no apparent disruption to theATPase transport function whereas
      variations to theATPase domain would be more critical.

PMID- 9562242
TI  - Non-enzymatic glycosylation of alkaline phosphatase alters its biological
      properties.
AB  - Hyperglycaemia in poorly controlled diabetic patients induces non-enzymatic
      glycosylation (glycation) of proteins, altering their structure and physiological
      bioactivity. Alkaline phosphatase (ALP) is a membrane-bound exoenzyme which faces
      the extracellular compartment. We have investigated the glycation of intestinal
      alkaline phosphatase in vitro and the consequences of such molecular
      modifications on certain structural and functional characteristics. The effect of
      glycation on alkaline phosphatase specific activity was determined after
      incubation of the enzyme with different sugars for various periods of time. The
      formation of early reversible glycation products was determined by the
      measurement of fructosamine levels, while the appearance of advanced glycation
      end products was estimated by spectrofluorometric analysis. A decrease in the
      specific activity of ALP was associated both with an increase in fructosamine
      levels and with the appearance of AGE-characteristic fluorescence. Changes in
      these parameters were found to depend on the incubation time, and on the
      concentration and glycating capability of the sugar employed. Co-incubation with
      aminoguanidine slowed down the appearance of protein-linked fluorescence, and
      additionally curbed the decrease in enzymatic specific activity. A significant
      correlation between the levels of ALP-fructosamine and ALP-advanced glycation end
      product was observed. Patterns of protein bands fractionated by SDS-PAGE were
      essentially identical for the nonglycated controls and the glycated samples. The
      electrophoretic mobility of the band of alkaline phosphatase on cellulose acetate
      gels increased as a function of the incubation time and the glycosylating power
      of the carbohydrate used. The present study provides evidence for the in vitro
      glycation of alkaline phosphatase, and for the consecutive alteration of its
      activity and structure.

PMID- 9562243
TI  - Influence of Aloe vera on collagen characteristics in healing dermal wounds in
      rats.
AB  - Wound healing is a fundamental response to tissue injury that results in
      restoration of tissue integrity. This end is achieved mainly by the synthesis of
      the connective tissue matrix. Collagen is the major protein of the extracellular
      matrix, and is the component which ultimately contributes to wound strength. In
      this work, we report the influence of Aloe vera on the collagen content and its
      characteristics in a healing wound. It was observed that Aloe vera increased the
      collagen content of the granulation tissue as well as its degree of crosslinking
      as seen by increased aldehyde content and decreased acid solubility. The type
      I/type III collagen ratio of treated groups were lower than that of the untreated
      controls, indicating enhanced levels of type III collagen. Wounds were treated
      either by topical application or oral administration of Aloe vera to rats and
      both treatments were found to result in similar effects.

PMID- 9562245
TI  - Amelioration of renal lesions associated with diabetes by dietary curcumin in
      streptozotocin diabetic rats.
AB  - Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma
      longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats
      for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the
      urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT,
      alkaline and acid phosphatases. The integrity of kidney was assessed by measuring
      the activities of several key enzymes of the renal tissue: glucose-6-phosphate
      dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose
      reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and
      membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria,
      activity of kidney ATPases and fatty acid composition of renal membranes in
      diabetic condition suggested that dietary curcumin brought about significant
      beneficial modulation of the progression of renal lesions in diabetes. These
      findings were also corroborated by histological examination of kidney sections.
      It is inferred that this beneficial ameliorating influence of dietary curcumin on
      diabetic nephropathy is possibly mediated through its ability to lower blood
      cholesterol levels.

PMID- 9562246
TI  - Characterization of multiple transcripts of the hamster dolichol-P-dependent N
      acetylglucosamine-1-P transferase suggests functionally complex expression.
AB  - The evolutionarily conserved dolichol-P-dependent N-acetylglucosamine-1-P
      transferase gene, ALG7, functions by initiating the dolichol pathway of protein N
      glycosylation. In yeast, ALG7 has a complex expression pattern and plays a
      critical role in diverse cellular functions, including proliferation and
      morphological response. In Chinese hamster ovary cells (CHO), ALG7 gives rise to
      three mRNAs of 1.5, 1.9 and 2.2 kb. We report results of RNA blotting assays,
      ribonuclease protection, PCR-amplification and sequencing of the CHO ALG7
      transcripts 5' and 3' ends which suggest that the 1.5 and 1.9 kb transcripts are
      produced as a consequence of initiation at 2 distinct start sites, 350-379 bp
      apart. The transcriptional start site for the 1.5 kb mRNA is positioned between
      the first two in frame ATGs, while that of the 1.9 kb species is located upstream
      of these two in-frame ATGs. In order to test the translational competence of the
      1.5 and 1.9 kb mRNAs, we constructed DNA templates specifying these transcripts
      and used them for in vitro transcription/translation. Our data show that the 1.9
      kb mRNA served in the synthesis of 36 and 24 kDa species, as well as a low
      abundance 32 kDa protein. The 1.5 kb transcript gave rise to a translation
      product of 32 kDa. The latter is synthesized in CHO cells and hamster
      submandibular glands. These results suggest the possibility that the 1.5 and 1.9
      kb transcripts give rise to related protein isoforms with different lengths of
      their NH2-terminal regions.

PMID- 9562244
TI  - Dexamethasone induced alterations in enzymatic and nonenzymatic antioxidant
      status in heart and kidney of rats.
AB  - This study was designed to investigate the alterations in thiobarbituric acid
      reactants (TBA-reactants) and enzymatic and nonenzymatic antioxidant levels
      induced by dexamethasone (Dex) in heart and kidney and to find out whether these
      alterations induced by Dex and its hypertensive effect had any role in the
      maintenance of hypertension in this model. Administration of dexamethasone
      induced severe loss of body weight, significant increase in heart and kidney
      weights and also marked electrocardiographic changes. The protein content in
      heart and kidney increased significantly during Dex administration and returned
      to near normalcy after withdrawal. Total activity of lactate dehydrogenase showed
      a significant increase in heart till day 8 of treatment, whereas in serum, it
      exhibited a significant decrease. The activity of CK in heart showed an increase
      till day 8 of treatment and approached normalcy thereafter. In serum, CK
      exhibited a decrease till day 8, remaining insignificant thereafter. CKMB in
      heart showed an insignificant increase initially, reaching normal levels on Dex
      withdrawal, whereas in serum, it showed a significant decrease throughout the
      experimental period. Mean arterial pressure (MAP) and heart rate increased
      significantly, while a significant elevation in the ST segment was noticed during
      administration as well as after withdrawal of Dex. The TBA-reactants levels were
      found to increase in heart and kidney during days 12 and 16 of administration
      with Dex and even after withdrawal of Dex, the levels were insignificantly
      elevated. The level of glutathione in heart and kidney increased from day 4
      onwards and reached normalcy during the later stages of treatment and after
      withdrawal of Dex. The total sulfhydryl groups exhibited a significant increase
      in both heart and kidney throughout the experiment. The antioxidant enzymes such
      as catalase, superoxide dismutase, glutathione peroxidase and glutathione S
      transferase exhibited a significant decrease in heart during Dex administration
      whereas, in kidney, they exhibited a significant increase during treatment and
      after withdrawal of Dex. Thus, Dex induced rise in mean arterial pressure,
      significant alterations in electrocardiographic parameters and also marked
      alterations in enzymatic and nonenzymatic antioxidant levels and in the TBA
      reactants level in heart and kidney.

PMID- 9562247
TI  - Reduction-oxidation (Redox) and vascular tissue level of homocyst(e)ine in human
      coronary atherosclerotic lesions and role in extracellular matrix remodeling and
      vascular tone.
AB  - Hyperhomocyst(e)inemia in patients with coronary and peripheral arterial
      occlusion has been demonstrated by others. Redox-state of homocyst(e)ine causes
      dysfunction of endothelial cells and promote growth of vascular smooth muscle
      cells. The role of tissue, protein bound and unbound, oxidative mixed disulfides
      in the development of fibrous plaque in atherosclerotic lesion is not known.
      Redox-state around the fibroblasts and vascular smooth muscle cells modulates the
      expression of extracellular matrix (ECM) components (Tyagi et al. 1996, J Cell
      Biochem, 61: 139-151). To determine the role of tissue homocystine in fibrotic
      atherosclerotic plaque development, coronary arteries were isolated from ischemic
      explanted hearts (n = 10). Apparently normal vascular tissue was obtained from
      idiopathic cardiomyopathic explanted hearts (n = 10). Tissue extract were
      prepared from atherosclerotic lesions and from normal arteries devoid of
      adventitia. Interaction of homocystine with Ellman's reagent (5, 5'-dithio-bis-2
      nitro benzoic acid) catalyzed by limiting amount of reducing agent (catalyst)
      generated change in optical density (OD) at 412 nm in dose dependent fashion. We
      have generated a standard curve between change at 412 nm and amount of
      homocystine. The change in OD at 412 nm with increasing amount (0-25 microg) of
      homocystine demonstrated linearity. The protein-bound oxidized disulfides were
      precipitated by trichloroacetic acid (TCA) and free-oxidative disulfides in the
      supernatant were collected. The pathophysiological amount of protein-bound
      disulfide in atherosclerotic tissue (1.0 +/- 0.2 microg/mg total protein) was 10
      times that in normal tissue (0.1 +/- 0.01 microg/mg, p < 0.001). The amount of
      free oxidative disulfide in atherosclerotic tissue (1.5 +/- 0.3 microg/mg) was 15
      times that in normal tissue (0.12 +/- 0.02 microg/mg, p < 0.001). To determine
      the role of homocystine in ECM expression, ECM collagenase activity in the
      presence and absence of homocystine was measured by zymography. The effect of
      homocysteine on collagenase activity was biphasic, increased at < [0.01 mM] and
      inhibited at > [0.1 mM]. To determine whether homocystine regulates vascular
      tone, isometric measurements were carried out using normal coronary rings.
      Results suggested that homocystine induced endothelial-modulated vasoconstriction
      in coronary vessels. Tissue oxidative disulfides and the homocystine may
      contribute to the development of fibrotic atherosclerotic lesions and vascular
      dysfunction.

PMID- 9562248
TI  - Sulfides impair short chain fatty acid beta-oxidation at acyl-CoA dehydrogenase
      level in colonocytes: implications for ulcerative colitis.
AB  - The disease process of ulcerative colitis (UC) is associated with a block in beta
      oxidation of short chain fatty acid in colonic epithelial cells which can be
      reproduced by exposure of cells to sulfides. The aim of the current work was to
      assess the level in the beta-oxidation pathway at which sulfides might be
      inhibitory in human colonocytes. Isolated human colonocytes from cases without
      colitis (n = 12) were exposed to sulfide (1.5 mM) in the presence or absence of
      exogenous CoA and ATP. Short chain acyl-CoA esters were measured by a high
      performance liquid chromatographic assay. 14CO2 generation was measured from [1
      14C]butyrate and [6-14C]glucose. 14CO2 from butyrate was significantly reduced (p
      < 0.001) by sulfide. When colonocytes were incubated with hydrogen sulfide in the
      presence of CoA and ATP, butyryl-CoA concentration was increased (p < 0.01),
      while crotonyl-CoA (p < 0.01) and acetyl-CoA (p < 0.01) concentrations were
      decreased. These results show that sulfides inhibit short chain acyl-CoA
      dehydrogenase. As oxidation of n-butyrate governs the epithelial barrier function
      of colonocytes the functional activity of short chain acyl-CoA dehydrogenase may
      be critical in maintaining colonic mucosal integrity. Maintaining the functional
      activity of dehydrogenases could be an important determinant in the expression of
      ulcerative colitis.

PMID- 9562249
TI  - Cloning of the cDNA and nucleotide sequence of a skeletal muscle protease from
      myopathic hamsters.
AB  - A neutral protease with an estimated Mr of about 26 kD and responsible for
      cleavage ofmyosin LC2 was isolated from hamster skeletal muscle. Complementary
      DNAs were generated by RT-PCR using total hamster muscle RNA and degenerate
      oligonucleotide primers based on the sequences of two internal peptides. The
      nucleotide sequences of the resultant cDNAs were subsequently determined and the
      complete amino acid sequence of the protease deduced. Although the hamster
      protein shared 63-85% identity in nucleotide and amino acid sequences with rat
      and mouse mast cell proteases, it had a higher degree of specificity for myosin
      LC2 than mast cell proteases which also digested myosin LC1 and myosin heavy
      chains. As a result, the hamster protease was designated mekratin because of its
      unique enzymatic specificities to distinguish it from other mast cell proteases.
      A polyclonal antibody was raised specific to the hamster muscle and human cardiac
      muscle mekratins without apparent cross-reaction with rat mast cell proteases. We
      have earlier demonstrated the presence in excess of a neutral protease that
      specifically cleaves LC2 in human hearts obtained at end stage idiopathic dilated
      cardiomyopathy (IDC). Western analyses revealed that heart tissue from patients
      with IDC contained 5-10 fold more mekratin than control samples. Furthermore, the
      level of the protease in human IDC tissues was similar to that seen in myopathic
      hamster skeletal muscle. No bands were recognized by the antibody when IDC
      myofibrils were probed due to the removal of soluble proteins during sample
      preparation. Thus, these results strongly suggest that the anti-mekratin antibody
      will provide positive identification of IDC in many cases and diagnosis by
      exclusion may be replaced.

PMID- 9562250
TI  - Receptor-Ck-dependent regulation of genes involved in the cell cycle.
AB  - The present study was addressed to understand the interrelationship between
      Receptor-Ck activation, mevalonate pathway and primary response genes such as c
      fos, c-myc and cyclin 'D' involved in the cell cycle. The results reported here
      unambiguously revealed that the phosphatidic acid (generated through the
      activation of Receptor-Ck by cholesterol) regulates mevalonate pathway, DNA
      synthesis as well as expression of genes coding for c-fos, c-myc and cyclin 'D'.
      By using the specific blockers of ras farnesylation as well as phospholipase D,
      it became apparent that phosphatidic acid regulates two processes: (a) activation
      of Gap-ras pathway leading to the expression of c-fos, c-myc proto-oncogenes
      probably through the activation of NF1 transcription factor; (b) cleavage of 125
      kDa endoplasmic reticulum protein leading to the generation of 47 kDa protein
      factor which not only regulates mevalonate pathway but also has an ability to
      heterodimerize with Receptor-Ck protein and this heterodimer may be responsible
      for the regulation of cyclin 'D' expression probably by binding to the SRE like
      sequence present in the promoter region of this gene. On the basis of these
      findings, we propose a pathway through which Receptor-Ck upon endocytosis
      regulate these primary response genes (c-fos, c-myc, cyclin 'D') involved in the
      cell cycle.

PMID- 9562251
TI  - Stability of the contractile assembly and Ca2+-activated tension in adenovirus
      infected adult cardiac myocytes.
AB  - Adenovirus-mediated gene transfer into adult cardiac myocytes in primary culture
      is a potentially useful method to study the structure and function of the
      contractile apparatus. However, the consequences of adenovirus infection on the
      highly differentiated state of the cultured myocyte have not been determined. We
      report here a detailed analysis of myofilament structure and function over time
      in primary culture and after adenovirus infection. Adult rat ventricular myocytes
      in primary culture were infected with a recombinant adenovirus vector expressing
      either the LacZ or alkaline phosphatase reporter gene. Control and infected
      myocytes were collected at days 0-7 post-isolation/infection, and myofilament
      isoform expression was determined by SDS-PAGE and Western blot. Laser scanning
      densitometry showed that the alpha- to beta-myosin heavy chain ratio, the
      stoichiometry of the myosin light chains and the expression of the adult troponin
      T isoform did not change over time in culture or with adenovirus treatment.
      Importantly, examination of Ca2+-activated tension in single myocytes showed no
      change in the shape or position of the tension-pCa relationship in the control
      and adenovirus infected myocytes during primary culture. These results indicate
      that the structure and function of adult cardiac myocytes are stable in short
      term primary culture and are not affected by adenovirus infection per se, and
      therefore provide the foundation for the use of adenovirus-mediated myofilament
      gene transfer to study contractile apparatus structure and function in adult
      cardiac myocytes.

PMID- 9562252
TI  - Release of nitric oxide and expression of constitutive nitric oxide synthase of
      human endothelial cells: enhancement by a 14-membered ring macrolide.
AB  - A 14-membered ring macrolide, erythromycin, acts not only as an antibacterial but
      also as an anti-inflammatory agent. We have previously reported that erythromycin
      modulates neutrophil functions and ameliorates neutrophil-induced endothelial
      cell damage through the action of cyclic AMP-dependent protein kinase (PKA) and
      nitric oxide (NO). We investigated the effect of erythromycin on human
      endothelial cell functions. Erythromycin enhanced intracellular calcium ion
      concentration ([Ca2+]i) of endothelial cells and NO release from endothelial
      cells. The enhancement of NO release from endothelial cells by erythromycin was
      abolished by addition of EGTA in the medium and was partially reduced by addition
      of H-89, an inhibitor of PKA. These results suggest that erythromycin enhances NO
      release from endothelial cells through the action of PKA and [Ca2+]i. In
      addition, constitutive NO synthase (cNOS) protein expression of endothelial cells
      was dose-dependently enhanced by treatment with erythromycin, which might also
      contribute to the enhancement of NO release from endothelial cells by
      erythromycin. The effect of erythromycin as an anti-inflammatory agent might be
      partially mediated through the enhancement of NO release from endothelial cells
      and the drug might be a useful tool for the investigation of cNOS of endothelial
      cells.

PMID- 9562254
TI  - Inactivation of protein kinase C in rat liver during late hypoglycemic phase of
      sepsis.
AB  - Changes in protein kinase C (PKC) (calcium- and phospholipid-dependent protein
      kinase) activity in rat liver during different metabolic phases of sepsis were
      studied. Sepsis was induced by cecal ligation and puncture (CLP). Experiments
      were divided into three groups: control, early sepsis, and late sepsis. Early and
      late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after
      CLP. Hepatic PKC was extracted and partially purified by ammonium sulfate
      fractionation and DEAE-cellulose chromatography. PKC activity was assayed based
      on the rate of incorporation of 32p from [gamma-32P]ATP into histone. The results
      show that during early sepsis, both membrane-associated and cytosolic PKC
      activities remained relatively unaltered. During late sepsis, membrane-associated
      PKC was unaffected while cytosolic PKC activity was decreased by 19.5-34.4%.
      Kinetic analysis of the data on cytosolic PKC during late phase of sepsis reveals
      that the Vmax values for ATP, histone, Ca2+, phosphatidylserine, and
      diacylglycerol were decreased by 23.4, 22.1, 19.5, 25, and 34.4%, respectively,
      with no changes in their Km values. These data indicate that cytosolic PKC
      activity was inactivated in rat liver during late hypoglycemic phase of sepsis.
      Since PKC-mediated phosphorylation plays an important role in regulating hepatic
      glucose metabolism, an inactivation of cytosolic PKC may contribute to the
      development of hypoglycemia during late phase of sepsis.

PMID- 9562256
TI  - Two- and three-dimensional computer graphic evaluation of the subacute spinal
      cord injury.
AB  - We have evaluated three-week-old compression lesions of the rat spinal cord using
      two-dimensional and three-dimensional morphometry, reconstruction, and
      visualization techniques. We offer a new computer assisted method to determine
      the number and density of macrophages within the spinal lesion using the
      macrophage specific monoclonal label ED1. We also provide quantitative
      information on pathological cyst formation and cavitation. This technique does
      not require: (1) subjective identification of the cell type, (2) human
      interaction with the data during the phase of quantification, and (3) can be
      applied to any sampling paradigm based on immunocytochemical labeling. Using
      novel algorithms based on solutions to 'correspondence' and 'branching' problems
      inherent in cross-sectional histological data, we provide three-dimensional
      reconstructions and visualizations of the macrophagic lesions and cysts imbedded
      within it. Our three-dimensional surface reconstructions can be interrogated to
      determine volumes and surface areas of structures within the data set. Using
      these methods we have learned that macrophage numbers approach the maximum
      density possible for such isodiametric cells (approximately 12 microm diameter)
      in the central lesion ranging from 4000-7000 cells per mm2 of lesion. At the time
      point studied, macrophage numbers would have peaked following the initial insult,
      and would not be expected to decline for several months. While the density of
      macrophages is highest in the region of most tissue damage, we show that the
      central regions of cavitated and cystic spinal parenchyma is not. We discuss how
      this density of cells may effect the secondary pathological responses of the
      spinal cord to injury.

PMID- 9562255
TI  - Enhanced NOR-1 gene expression by exposure of Chinese hamster cells to high
      density 50 Hz magnetic fields.
AB  - Enhanced expression of neuron derived orphan receptor (NOR-1) gene was observed
      by exposure of Chinese hamster ovary K1 (CHO-K1) cells to an extremely low
      frequency magnetic field (ELFMF) of 50 Hz at 400 mT, but not at 5 mT. The
      enhanced expression, reaching the maximum at 6 h, was transient and reduced to
      the control level after exposure to 400 mT ELFMF for 24 h. The NOR-1 expression
      induced by treatment with forskolin and TPA was further enhanced by the
      simultaneous treatment with 400 mT ELFMF, in which the maximum response was at 3
      h. The NOR-1 expression by these treatments was induced more earlier than that by
      400 mT ELFMF alone. When cells were treated with an inhibitor of the protein
      kinase C (calphostin C or crocetin) and Ca2+ entry blockers (nifedipin and
      dantrolen) during the 400 mT ELFMF exposure, the enhanced NOR-1 expression was
      not observed. Exposure of CHO-K1 cells to the high-density 400 mT ELFMF may
      affect the signal transduction in the cells, resulting in the enhanced NOR-1 gene
      expression.

PMID- 9562257
TI  - New variant Creutzfeldt-Jakob disease.
AB  - Since the report of new variant Creutzfeldt-Jakob Disease (nvCJD) in humans last
      year, the search was on for direct evidence to link the condition to Bovine
      Spongiform Encephalopathy (BSE). The first case nvCJD was noted 10 years after
      the recognition of BSE in UK cattle. A direct link is now established. There are,
      however, some 'protective' mechanisms, the most important of which are the
      inefficiency of the gastric route of introducing the infected material, the
      species barrier and genetic 'predisposition'. None of these is full proof and
      time will tell whether feeding ruminants with their own species will turn out to
      be a major public health disaster?

PMID- 9562258
TI  - Maternal anticipation in Machado-Joseph disease (MJD): some maternal factors
      independent of the number of CAG repeat units may play a role in genetic
      anticipation in a Japanese MJD family.
AB  - We studied the relationship between the number of CAG repeat units in the MJD1
      gene and clinical features of Machado-Joseph disease (MJD) in eight patients from
      two generations of a Japanese MJD family. Because of lack of characteristic
      clinical signs of MJD such as dystonia, bulging eyes or facial myokymia, clinical
      diagnosis of MJD in this family was difficult to make prior to molecular testing
      for the CAG repeat expansion in the MJD1 gene. All the patients exhibited
      maternal transmission of MJD, and the intergenerational change in the number of
      CAG repeat units in the MJD1 gene was very small (+0.5+/-0.3, mean+/-S.E.M., n=4)
      in spite of marked genetic anticipation (-17.0 years/generation). In the present
      family, the degree of anticipation per repeat unit in maternal transmissions was
      much larger than that in maternal transmissions in the other six MJD families.
      This indicates that some maternal factors other than the increase of the number
      of CAG repeat units, which is known to be the basis of anticipation, may play a
      role in genetic anticipation in this MJD family.

PMID- 9562259
TI  - Epidemiology of motor neuron disease in the Kii Peninsula of Japan, 1989-1993:
      active or disappearing focus?
AB  - During the period 1989-1993, the incidence and migration patterns of patients
      with motor neuron diseases (MND) in Wakayama Prefecture, including one of the
      high-incidence Kii Peninsula foci ('Kozagawa focus'), were surveyed to determine
      whether the focus had truly disappeared or not. Overall, the crude average annual
      incidence was 1.43 per 100000 population; when age-adjusted to the 1990 Japanese
      population, it was 1.25 (1.85 for males and 0.61 for females). The average annual
      age- and sex-specific incidence steadily increased to a peak between 60 and 69
      years and dropped after 70. Geographically, the rates varied in the five regions
      of Wakayama Prefecture from 0.38 to 2.48. The areas with high incidence were
      distributed in the central and southernmost regions; the highest was in the
      Kozagawa focus with 9.54 (two ALS cases within five years; 4193 base population,
      1990). During the study period, four emigrants from Kozagawa had developed MND
      one to four decades after leaving the focus. Although the remarkable clustering
      of MND was thought to have disappeared, the southern Kii Peninsula remains a high
      risk area for MND, especially if one interprets the data so as to include the
      emigrants. In general, the age at onset has increased in the past 20 years from
      56.5 to 61.7; male predominance is observed.

PMID- 9562261
TI  - Expression of three calpain isoform genes in human skeletal muscles.
AB  - Calpain is thought to be involved in muscular degradation in progressive muscular
      dystrophy (PMD), especially Duchenne and Becker muscular dystrophies. To assess
      the expression of calpain genes in skeletal muscles of patients with myopathies,
      we examined mRNA levels of three calpain isoforms by the quantitative reverse
      transcriptase-polymerase chain reaction method in biopsied muscles from control,
      PMD and amyotrophic lateral sclerosis (ALS) patients. There was a statistically
      significant increase in calpain 1 and calpain 2 mRNA levels in PMD and ALS
      patients as compared to controls. In contrast, there was a decrease in expression
      of calpain 3 mRNA in PMD, but it was not statistically significant. Expression of
      calpain 1 and calpain 2 positively correlated with each other, but not with
      calpain 3. These results indicate that expression of calpain 1 and calpain 2, but
      not calpain 3, are upregulated in diseased human muscles, likely playing a
      regulatory role in the process of myofibrillar degradation at the transcriptional
      as well as posttranslational level.

PMID- 9562260
TI  - 677C to T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene
      and plasma homocyst(e)ine levels in patients with TIA or minor stroke.
AB  - It was the aim of this study to determine the associations of clinical and
      laboratory data with plasma homocyst(e)ine levels in patients with transient
      ischemic attack (TIA) or minor stroke (MS), with special reference to their 677C
      to T mutation status in the 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR)
      gene. Seventy-six patients with TIA or MS were investigated at least 3 months
      after their (last) clinical event. By means of univariate analysis, significant
      correlations of homocyst(e)ine levels with male gender (P<0.02), age (P<0.0005),
      creatinine levels (P<0.0002), folate levels (inversely, P<0.05), and alcohol use
      (P<0.02) were found, but not with vitamin B12 levels. Multivariate regression
      analysis, including age, creatinine levels, and folate levels as independent
      variables, revealed age (P<0.01) and creatinine levels (P<0.02) to be
      significantly correlated with homocyst(e)ine levels. After adjustment for age,
      creatinine levels and homocyst(e)ine levels remained significantly correlated to
      each other (P<0.005), whereas the relation between folate levels and
      homocyst(e)ine levels was no longer significant (P=0.10). Mutation-positive
      patients exhibited moderately and statistically non-significantly higher
      homocyst(e)ine levels than mutation-negative patients, particularly those who
      were homozygous positive. Homocyst(e)ine levels were closely correlated with
      creatinine levels (P<0.0002) and with folate levels (inversely, P<0.05), but only
      in mutation-positive and not in mutation-negative patients. Homozygous positive,
      heterozygous positive, and mutation-negative patients did not differ with respect
      to clinical and laboratory data concerning 'risk factors for stroke' or co
      existing vascular disease. In conclusion, the associations of creatinine levels
      and, inversely, of folate levels with plasma homocyst(e)ine levels in patients
      with TIA or MS are dependent on the 5,10-MTHFR mutation status. Significant
      correlations between these variables were found only in mutation-positive but not
      in mutation-negative patients.

PMID- 9562262
TI  - Interleukin-15, a T-cell growth factor, is expressed in human neural cell lines
      and tissues.
AB  - Interleukin-15 (IL-15) is a novel cytokine which shares activities and receptor
      components with IL-2. To investigate the biological roles of IL-15 in the human
      nervous system, we examined the expression of mRNAs for IL-15 and the IL-15
      receptor three subunits (IL-15alpha, IL-2Rbeta and IL-2Rgamma) in human neural
      cell lines and tissues using reverse transcription-polymerase chain reaction and
      Southern blot analysis. The constitutive expression of high levels of IL-15 mRNA
      was observed in all the cell lines examined, including Y79 retinoblastoma, IMR-32
      neuroblastoma, SK-N-SH neuroblastoma, U-373MG glioma, KG-1-C glioma, NTera2
      teratocarcinoma and neurons derived from NTera2 cells following treatment with
      retinoic acid (RA). Among these cell lines, IL-15 protein was detectable at high
      levels in culture supernatants of SK-N-SH cells and NTera2-derived neurons. The
      expression of an alternatively-spliced transcript of the IL-15 gene was up
      regulated in NTera2 cells during RA-induced neuronal differentiation, suggesting
      the existence of differentiation-dependent transcriptional regulation. The
      expression of IL-15 mRNA was also identified in the human cerebral and cerebellar
      tissues, peripheral nerve and skeletal muscle, while the mRNAs for the complete
      set of IL-15R components were detectable only in U-373MG cells, cerebral and
      cerebellar tissues at significant levels. These results indicate that the
      expression of IL-15 but not of IL-15R mRNA is universal in human neural cell
      lines and tissues and raise the possibility that IL-15 acts as a neuroimmune
      regulatory factor in the human central nervous system.

PMID- 9562253
TI  - Gene disruption in mice: models of development and disease.
AB  - Gene targeting technology in mice by homologous recombination has become an
      important method to generate loss-of-function of genes in a predetermined locus.
      Although the inactivation is limited to irreversible alteration of chromosomal
      DNA and a surprising variety of genes have given unexpected and disappointing
      results, modification of the basic technology now provides additional choices for
      a more specific and variety of manipulations of the mouse genome. This includes
      conditional cell-type specific gene targeting, knockin technique and the
      induction of the specific balanced chromosomal translocations. In the past decade
      this technique not only generated a wealth of knowledge concerning the roles of
      growth factors, oncogenes, hormone receptors and Hox genes but also helped to
      produce animal models for several human genetic disorders. In the future it may
      provide more powerful and necessary tools to dissect the psychiatric disorders,
      understanding the complex central nervous system and to correct the inherited
      disorders.

PMID- 9562263
TI  - Anti-Hu-associated paraneoplastic sensory neuropathy with peripheral nerve
      demyelination and microvasculitis.
AB  - A patient had a paraneoplastic autonomic, then sensory, then sensory-motor
      neuropathy with small cell lung carcinoma and a high titer Anti-Hu antibody to
      nuclei of neuronal cells. As an unusual finding there was electrophysiological
      and pathological evidence of demyelination and a peripheral nerve
      microvasculitis. The relationship of microvasculitis and peripheral nerve
      demyelination is discussed and their occurrence with paraneoplastic anti-Hu
      associated sensory neuropathy is suggested not to be by chance.

PMID- 9562264
TI  - Photic stimulation-induced alteration of brain energy metabolism measured by 31P
      MR spectroscopy in patients with MELAS.
AB  - We examined brain energy metabolism by phosphorus-31 magnetic resonance
      spectroscopy (31P-MRS) in the occipital cortex in a mother and a daughter with
      MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like
      episodes) during photic stimulation. The peak area ratio of phosphocreatine
      markedly decreased during photic stimulation, and subsequently increased after
      the stimulation. This method, photic stimulation-31P-MRS, may be useful in
      assessing brain energy metabolism in neurological diseases.

PMID- 9562265
TI  - Clinical correlate and fine specificity of anti-GQ1b antibodies in peripheral
      neuropathy.
AB  - We studied the frequency, fine specificity and clinical correlate of anti-GQ1b
      IgG and IgM antibodies in 216 patients with neuropathy including three with
      Miller Fisher syndrome (MFS), 73 with Guillain-Barre syndrome (GBS), 99 with
      neuropathy associated with IgM monoclonal gammopathy (PN+IgM) and 41 with other
      neuropathies, and compared the data with 92 disease or normal controls. We found
      high (>1/100) anti-GQ1b IgG titers in all three MFS patients and in two GBS
      patients (2.7%) with ophthalmoplegia and ataxia, while high anti-GQ1b IgM were
      only found in two patients with a chronic demyelinating sensorimotor neuropathy
      associated with IgMkappa monoclonal gammopathy (2%). By overlay HPTLC, IgG
      antibodies in MFS and GBS either selectively reacted with GQ1b or also bound to
      GD3, and less intensely to GD1b, while IgM antibodies from both patients with
      PN+IgM also strongly reacted with GD1b and, in one, with GD3 and GT1b. The
      constant association of anti-GQ1b antibodies with dysimmune neuropathies and the
      correlation between their isotype, fine specificity and clinical presentation,
      support a possible pathogenetic link between these antibodies and the neuropathy.

PMID- 9562266
TI  - Cerebrospinal fluid carnitine levels in patients with Alzheimer's disease.
AB  - We assessed free carnitine (FC) and acylcarnitine esters (AC) in both
      cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria
      for Alzheimer's disease (AD), and from 28 healthy matched-controls. We found no
      significant correlation between FC and AC levels in CSF. FC and AC levels in CSF
      did not differ significantly between AD patients and controls, but plasma FC
      levels were significantly lower in AD patients. CSF and plasma FC and AC levels
      did not correlate with age, age at onset of AD, duration of AD, and scores of the
      Minimental State Examination of Folstein. Although these results suggest that CSF
      carnitine levels are apparently unrelated with the risk for AD, the trend of the
      FC/AC ratio to be higher in AD patients might suggest the possibility of a lower
      carnitine acetyltransferase activity in AD, as previously reported in some brain
      areas.

PMID- 9562267
TI  - The expression of nitric oxide synthases in human brain tumours and peritumoral
      areas.
AB  - Nitric oxide, a potent signalling molecule produced from L-arginine by nitric
      oxide synthase (NOS), has been implicated in diverse pathophysiological
      processes. Many characteristics of malignant tumours such as increased vascular
      permeability, vasodilation, neovascularisation and free radical injury to the
      tumour and adjacent normal tissues are believed to be mediated by nitric oxide.
      While NOS expression has been demonstrated in brain tumours, no equivalent
      studies have yet been reported on the adjacent peritumoral brain region. The
      present study examined the pattern of NOS expression in the human tumour and
      peritumoral brain areas. Biopsies were obtained from eight patients (six gliomas,
      one each of meningioma and metastatic adenocarcinoma) from three areas: tumour,
      peritumoral, and apparently 'normal' adjacent brain tissue. Immunohistochemical
      staining was performed for three isoforms of NOS: brain NOS (BNOS), endothelial
      NOS (ENOS) and macrophage-specific NOS (MacNOS). Except for glioblastoma
      multiforme and metastatic adenocarcinoma, the tumour cells expressed all three
      NOS isoforms. In four tumours, there was a demonstrable gradient of ENOS
      expression falling away from the tumour. In three gliomas, many glial cells were
      intensely labelled with BNOS. This labelling decreased in the peritumoral
      tissues. In four tumours, cells (presumably lymphocytes, and CD 45 positive
      macrophages) were labelled intensely with MacNOS in and around the blood vessels.
      These results suggest that nitric oxide is produced in the tumour cells and
      endothelium of tumour vasculature, while occasionally glial cells may also be
      induced to produce it. The possible role of nitric oxide in the production of
      peritumoral oedema is discussed.

PMID- 9562268
TI  - Optic ataxia following unilateral stroke.
AB  - Five patients with optic ataxia together with tactile apraxia are described. They
      also demonstrated difficulty in finger movements under visual guidance. The CT
      scan showed lesions in the posterior parietal region in three and in two they
      were located anteriorly. It is well recognised that lesions in the posterior
      parietal area may cause disruption of visual guided movements. On the basis of
      the two cases it is postulated that the same phenomenon could occur with lesions
      located more anteriorly. The assumption is that optic ataxia may occur either
      following damage to the parieto-occipital region or to disruption of its
      occipitofrontal connections.

PMID- 9562269
TI  - Aphagia due to pharyngeal constrictor paresis from acute lateral medullary
      infarction.
AB  - Although swallowing difficulties (dysphagia) frequently occur in acute brainstem
      infarction, physiological studies of dysphagia (videofluoroscopy, manometry) are
      rarely reported. We present a patient with ipsilateral Horner's syndrome, palatal
      and laryngeal weakness, aphagia, and ipsilateral face and contralateral extremity
      pin and temperature loss due to lateral medullary infarction confined to the
      rostral dorsolateral medulla (RDM). Videofluoroscopy showed that the patient was
      unable to initiate a swallow. Manometry showed a markedly reduced peak pharyngeal
      pressure and weak pharyngeal contractions. Within 20 months, the patient's
      neurological deficits resolved, videofluoroscopy showed a normal swallow, and
      manometry showed normal peak pharyngeal pressure. Correlation of the clinical,
      physiological, and imaging evaluations shows that aphagia and severe bilateral
      pharyngeal paresis can result from unilateral RDM infarction. We suggest that, in
      man, the bilateral medullary swallowing centers function as one integrated
      center, and that infarction of a portion of this center is sufficient to cause
      complete loss of swallowing.

PMID- 9562270
TI  - Acute thyrotoxic neuropathy--Basedow's paraplegia revisited.
AB  - A forty seven year old woman with previously undetected goitre, developed thyroid
      storm in the immediate postoperative period. Forty eight hours after undergoing
      nephrolithotomy for renal calculus, she was noted to have flaccid areflexic
      quadriparesis, most marked in the lower limbs. Electrophysiologic studies
      revealed evidence of an asymmetric, mixed axonal and demyelinating, motor-sensory
      peripheral neuropathy. Ultrastructure of the sural nerve showed predominant
      abnormalities in the mitochondria and cytoskeletal elements compatible with
      thyrotoxicosis. Treatment of thyrotoxicosis coincided with recovery of symptoms.
      We believe that thyrotoxicosis precipitated an acute polyneuropathy the
      ultrastructure of which is being described for the first time.

PMID- 9562271
TI  - Stroke from internal carotid artery occlusion during mumps infection.
AB  - During the terminal incubation period of severe mumps infection, a 40-year-old
      patient suffered from large infarction in the right middle cerebral artery
      territory. The proximal right internal carotid artery (ICA) was occluded on
      angiography. Computed tomography of the neck detected a hemorrhage located
      ventromedial to the right common carotid artery. Four months later the right ICA
      was partly recanalized. Carotid surgery revealed an atherosclerotic plaque and a
      vessel wall, which was fragile and less compact than usually. A strong
      inflammatory reaction to mumps infection may have contributed to the pathogenesis
      of the cervical hemorrhage and to acute thrombosis and occlusion of the ICA.

PMID- 9562272
TI  - Juvenile Leigh syndrome with protracted course presenting as chronic sensory
      motor neuropathy, ataxia, deafness and retinitis pigmentosa: a
      clinicopathological report.
AB  - We herein describe a male patient who died at 37 years of age, after having
      suffered from a slowly progressive syndrome of chronic sensory motor neuropathy,
      deafness, retinitis pigmentosa and ataxia. The neuropathological study showed
      symmetric areas of necrosis and demyelination affecting the cerebellum and
      brainstem. The type of lesion was consistent with the characteristics of Leigh
      Syndrome. On the basis of the histology of the lesions, we believe that they
      appeared only a few months before the death of the patient. We underline the
      atypical clinical picture and suggest that, in certain cases, brain MRI may not
      be a reliable diagnostic tool.

PMID- 9562273
TI  - Acute inflammatory demyelinating polyradiculoneuropathy associated with
      hyperIgEemia and atopic dermatitis.

PMID- 9562274
TI  - Neurology and health planning.

PMID- 9562275
TI  - Simultaneous aortic and renal revascularisation: a review of risk and benefit.

PMID- 9562276
TI  - Changes in thyroid function and immunological parameters long after subtotal
      thyroidectomy for Graves' disease.
AB  - OBJECTIVE: To find out whether subtotal thyroidectomy results in long term stable
      functional and immunological remission in patients with Graves' disease. DESIGN:
      Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 176 patients
      who underwent subtotal thyroidectomy for Graves' disease, 1970-79. INTERVENTION:
      Follow up surveys in 1984 and 1992. MAIN OUTCOME MEASURES: Changes in thyroid
      function, antibody titres, and lymphocyte subsets. RESULTS: 29/79 patients (39%)
      who were euthyroid in 1984 had evidence of thyroid dysfunction in 1992. Of the 8
      patients with latent hypothyroidism in 1984, 3 (38%) had become euthyroid by
      1992, and none required treatment. Of the 29 patients who were hypothyroid in
      1984, 5 had latent hypothyroidism and 1 was euthyroid in 1992, and of the 18
      patients with recurrent hyperthyroidism in 1984, 1 had become euthyroid by 1992.
      The number of positive titres to TSH-binding inhibitory immunoglobulin was
      significantly higher in the recurrence group (31/36, 86%) compared with the
      hypothyroid (7/26, 27%), latent hypothyroidism (8/37, 22%), and euthyroid (22/77,
      29%) groups (p < 0.01). There were also significant differences in the mean (SD)
      number of Leu HLA DR subsets between the control (17 (3), n = 18) and recurrence
      (21 (6), n = 38), hypothyroid (22 (6), n = 35), latent hypothyroidism (22 (6), n
      = 22), and euthyroid (22 (9), n = 64) groups (p < 0.002). There were no
      differences in the number of T cell subsets among the groups. CONCLUSION:
      Treatment of Graves' disease by subtotal thyroidectomy does not necessarily
      result in stable late functional or immunological remission. Long term follow up
      of such patients may be necessary.

PMID- 9562277
TI  - Effects of occlusive and conventional gauze dressings on incisional healing after
      abdominal operations.
AB  - OBJECTIVE: To compare the effect of occlusive (Comfeel) and conventional (Mepore)
      dressings on the healing of incisional wounds after abdominal operations. DESIGN:
      Prospective randomised study. SETTING: Laboratory and teaching hospital, Denmark.
      SUBJECTS: 73 patients who underwent clean operations requiring incisions longer
      than 5 cm between August 1993 and August 1995 were randomised to have their
      wounds dressed with either Comfeel or Mepore. INTERVENTIONS: Comfeel was left on
      until the sutures were removed, and Mepore was removed 2 days postoperatively.
      MAIN OUTCOME MEASURES: Infection, adherence, leakage, and cosmetic appearance
      three months later. RESULTS: 36 patients were randomised to have Comfeel and 37
      to have Mepore. 29 patients were withdrawn from the study (20 having Mepore and 9
      having Comfeel) leaving 26, and 17 for analysis, respectively. Wound infections
      developed in 1 patient in the Comfeel group and 5 in the Mepores group (p = 0.2).
      There were no differences between the groups regarding the need for dressings to
      be changed, the incidence of leakage, or loosening of the dressing from the skin.
      Comfeel adhered securely to the skin and remained more or less transparent until
      sutures were removed. It remained totally transparent in 23 (64%), and no
      dressing became totally opaque. There were no differences in cosmetic appearance
      after three months. We had the impression that patients who had Comfeel were more
      comfortable and found it easier to mobilise and carry out their daily activities.
      CONCLUSION: Occlusive dressings stay in place and stay transparent, and do not
      increase the risk of wound infection. They may even be more comfortable. they are
      a reasonable alternative to conventional dressings.

PMID- 9562279
TI  - Prosthetic repair of femoral hernia: audit of long term follow-up.
AB  - OBJECTIVE: To study the long term results of 93 femoral hernia repairs by
      cylindrical prothesis with a polypropylene mesh. DESIGN: Prospective open study.
      SETTING: District hospital, Spain. SUBJECTS: 92 patients who had 93 hernias
      repaired between 1989 and 1992. INTERVENTIONS: Lichtenstein repair of femoral
      hernias. MAIN OUTCOME MEASURES: Complications and recurrences. RESULTS: The mean
      follow up was 64 months (range 43-84). There was one recurrence 4 months
      postoperatively in a patient who had been operated on as an emergency for an
      incarcerated hernia, and in one patient the prosthesis had to be removed 10 days
      after the initial operation. This was subsequently repaired with polypropylene
      mesh and had not recurred at 4 years. CONCLUSION: Herniorrhaphy with cylindrical
      prosthesis is our preferred elective technique for repair of primary femoral
      hernias although other techniques are advisable for incarcerated or recurrent
      hernias.

PMID- 9562278
TI  - Systemic cytokine response to hepatic resections under total vascular exclusion.
AB  - OBJECTIVE: To investigate the systemic cytokine response to major liver surgery
      as the basis for assessing potential new treatments. DESIGN: Open prospective
      study. SETTING: University hospital, UK. SUBJECTS: Thirteen patients undergoing
      elective hepatic resections that involved total vascular exclusion of the liver.
      INTERVENTIONS: Blood samples were taken preoperatively, during the operation, and
      during the first four postoperative days. Concentrations of endotoxin, interferon
      gamma (IFN-gamma), tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL-1),
      and interleukin-6 (IL-6) were measured. RESULTS: Endotoxin concentrations were
      raised in 3/13 patients before operation and in 6 patients during the
      postoperative period. TNFalpha concentrations were undetectable. IFN-gamma and IL
      1 responses followed a low and inconclusive pattern. IL-6 was significantly
      increased from 6 hours after operation to the third postoperative day, peaking at
      699 (+/-277) pg/ml at 24 hours (p < 0.01). The two patients who died had the
      highest postoperative concentrations of IL-6. CONCLUSIONS: There is a pronounced
      systemic response to hepatic resection under total vascular exclusion that is
      reflected by the increase in IL-6 concentration and correlates with the operative
      blood loss and postoperative outcome. This might be used as an indicator of the
      response to specific treatments in this type of surgery. Treatments that minimise
      the IL-6 response to major hepatic resection may be of value.

PMID- 9562280
TI  - Acute mesenteric vascular occlusion: analysis of 39 patients.
AB  - OBJECTIVE: To study the factors that influence mortality and long term outcome of
      patients with acute mesenteric vascular occlusion. DESIGN: Retrospective study.
      SETTING: University hospital, Kanazawa, Japan. PATIENTS: Thirty-nine patients
      treated between 1978 and 1995 for acute mesenteric vascular occlusion.
      INTERVENTIONS: 34 patients underwent laparotomy. Bowel was resected in 29
      patients, and primary anastomosis was done in 20. The occluded vessel was
      revascularised in 5 patients. MAIN OUTCOME MEASURES: mortality, short bowel
      syndrome and long term survival. RESULTS: 25 patients had arterial occlusions,
      and 8 venous. In the remaining 6, the occluded vessel was not identified. 11
      Patients developed renal failure, 11 respiratory failure, and 10 disseminated
      intravascular coagulation (DIC). Twelve patients died within 30 days. The factors
      associated with early death were acidosis and high serum amylase activity. 9
      Patients developed the short bowel syndrome. Survival was 49% at 1 year, and 34%
      at 5 years. CONCLUSION: Mortality was higher in patients with advanced
      peritonitis. Mesenteric revascularisation should be attempted to avoid the short
      bowel syndrome.

PMID- 9562281
TI  - Influence of ultrasound on clinical decision making in acute appendicitis: a
      prospective study.
AB  - OBJECTIVE: To assess the efficacy of ultrasound (US) as part of an algorithm to
      establish the indication for laparotomy in patients with suspected acute
      appendicitis. DESIGN: Prospective investigation. SETTING: University department
      of surgery, Germany. SUBJECTS: 669 unselected patients admitted with suspected
      acute appendicitis. INTERVENTIONS: Clinicopathological and procedural diagnoses
      of the algorithm were evaluated by correlating clinical and US findings with the
      results of laparotomy in 171 patients of whom 143 had acute appendicitis
      (prevalence 21%), and clinical as well as follow up data in the remainder. MAIN
      OUTCOME MEASURES: The major clinicopathological variables were accuracy and
      positive predictive value; the rate of negative laparotomies and that of bad
      diagnostic errors served as the main procedural variables. RESULTS: The overall
      sensitivity, specificity, and accuracy of the clinical diagnosis were 0.503,
      0.950, and 0.855, respectively (positive predictive value: PPV 0.734, negative
      predictive value: NPV 0.875), those of ultrasound: 0.797, 0.967, and 0.931 (PPV
      0.870, NPV 0.946); and 0.853, 0.927, and 0.940 at the end of the algorithm (PPV
      0.762, NPV 0.958). However, the algorithm would have resulted in a significant
      increase in the rate of unnecessary laparotomies (from 13% to 16%). A revised
      clinical algorithm gave an overall diagnostic accuracy of 0.940 (p < 0.001)
      together with a low rate of negative laparotomies (11%, p < 0.01) and a
      significantly reduced number of diagnostic errors (from 71 to 21, p < 0.001).
      CONCLUSION: Ultrasonography enabled us to diagnose acute appendicitis in more
      patients more often and more quickly than clinical evaluation alone, suggesting
      that US may produce a better outcome. The revised clinical algorithm may be
      helpful in the study of US in patients with suspected acute appendicitis in
      prospective randomised controlled clinical trials.

PMID- 9562282
TI  - Haemostatic aspects of recombinant human erythropoietin in colorectal surgery.
AB  - OBJECTIVE: To find out whether recombinant human erythropoietin (r-HuEPO) given
      perioperatively has any effect on haemostatic activity in patients undergoing
      elective colorectal resection. DESIGN: A placebo-controlled double-blind study.
      SETTING: Odense university hospital, Denmark. SUBJECTS: 24 patients undergoing
      elective colorectal resection, 13 of whom were given r-HuEPO (Eprex) and 11
      placebo. MAIN OUTCOME MEASURES: Concentrations of haemoglobin, tissue-type
      plasminogen activator and plasminogen activator inhibitor-1; activated partial
      thromboplastin time; prothrombin time; platelet and reticulocyte counts; blood
      loss; and transfusions. RESULTS: There was no significant change in fibrinolytic
      activity, prothrombin time, or activated prothrombin time in the treatment group.
      Platelet counts differed slightly but not significantly, being higher in the r
      HuEPO group. There was a significant increase in reticulocyte counts in the r
      HuEPO group. CONCLUSION: R-HuEPO given perioperatively significantly increased
      erythropoiesis in patients undergoing elective colorectal operations but had no
      influence on haemostatic activity.

PMID- 9562283
TI  - Severe sepsis in cardiac surgical patients.
AB  - OBJECTIVE: To elucidate the incidence, determinants, and consequences of severe
      sepsis after cardiac surgery. DESIGN: Prospective study. SETTING: Cardiac
      surgical unit, Greece. SUBJECTS: 2615 adult patients having cardiac operations.
      MAIN OUTCOME MEASURES: Microbiological evidence of sepsis, mortality, and
      duration of stay in the intensive care unit (ICU) and hospital. RESULTS: Severe
      sepsis developed in 41/2615 patients (2%), all during their stay in the ICU:
      there were 30 men and 11 women, mean (SD) age 65 (10) years. It was most common
      after combined coronary artery bypass grafting and valve-related operations
      (7/95, 7%), followed by miscellaneous cardiac operations (7/147, 5%), valve
      replacement (8/359, 2%), and coronary artery bypass grafting (19/2014, 1%). When
      the 41 patients who developed severe sepsis were compared with those who did not
      (n = 2574) by univariate analysis, there were significant differences in age (p =
      0.004); type of operation (p < 0.0001); duration of operation (p < 0.001);
      bleeding that necessitating either reoperation or significantly more blood
      transfused (p < 0.0001); and the incidence of low cardiac output syndrome (p =
      0.0001). Of the 41 patients with severe sepsis, 19 (46%) had serious operative
      complications, 40 (98%) had severe complications in the ICU, and 16 (39%)
      required reintubation for hypoxaemia. Among the 41 there were 54 bacteraemic
      episodes of which 37 (69%) were caused by gram positive cocci, 6 (11%) by gram
      negative bacteria, and 11 (20%) by Candida albicans. Staphylococcus epidermidis
      was the most common pathogen isolated (n = 26, 48%). Sepsis associated with
      bacterial infection usually developed during the first two weeks, and that caused
      by fungal infection was most common after the twentieth postoperative day.
      Patients with severe sepsis required longer mechanical ventilation (31 (21) days
      compared with 0.9 (0.1) days); longer stay in the ICU (40 (25) days) compared
      with 2 (1) days); longer stay in hospital (48 (27) days compared with 10 (2)
      days); and significantly more of them died (13 (32%) compared with 41 (2%), p <
      0.0001 in each case). CONCLUSIONS: We concluded that severe sepsis mainly
      developed in cardiac surgery patients with serious operative and postoperative
      complications and was associated with a longer stay in both ICU and hospital, and
      a higher mortality.

PMID- 9562284
TI  - Microbial translocation and impairment of mucosal immunity induced by an
      elemental diet in rats is prevented by selective decontamination of the digestive
      tract.
AB  - OBJECTIVE: To assess the effect of selective decontamination of the digestive
      tract (SDD) on intestinal secretory immunoglobulin A (sIgA) concentrations in a
      model of intestinal bacterial overgrowth and bacterial translocation induced by
      an elemental diet in rats. DESIGN: Laboratory study. SETTING: University
      hospital, Germany. MATERIAL: 45 specific pathogen free female Crl:CD(R) BR rats.
      INTERVENTIONS: For 7 days, 3 groups of rats were fed orally with standard chow (n
      = 15), total parenteral nutrition solution (ORAL-TPN, n = 15), or ORAL-TPN plus
      tobramycin (20 mg/L) and polymyxin E (25 mg/L) (ORAL-TPN + SDD). MAIN OUTCOME
      MEASURES: Bacterial translocation to mesenteric lymph nodes (MLN), numbers of
      gram negative enterobacteria and total aerobic bacteria in the caecum, and
      intestinal concentrations of sIgA. RESULTS: The incidence of bacterial
      translocation was significantly increased in the group given ORAL-TPN (8/15, 53%)
      compared with the group given chow (1/15, 7%, p < 0.01). Supplementation of ORAL
      TPN with SDD reduced translocation to 0/15. The ORAL-TPN group had a pronounced
      overgrowth of aerobic bacteria in the caecum, mainly by gram negative
      enterobacteria, which was prevented by the SDD. The concentrations of intestinal
      sIgA were significantly reduced in the ORAL-TPN group. SDD resulted in both the
      soluble and insoluble sIgA fractions in the gut being within the reference
      ranges. CONCLUSION: SDD prevents gram negative caecal overgrowth and
      translocation to MLN in rodents fed on ORAL-TPN. The significantly reduced
      mucosal immunity caused by ORAL-TPN alone is restored by SDD, although one might
      have expected a further reduction in sIgA concentrations with lower microbial
      populations than in the ORAL-TPN group. Not only does SDD not seem to affect the
      mucosa associated immune system adversely, but also depressed mucosal immunity
      was restored.

PMID- 9562285
TI  - A modified technique for tying the one-handed knot.

PMID- 9562286
TI  - Rectal endometriosis: transanal endoscopic microsurgery or laparoscopic
      resection?

PMID- 9562287
TI  - Rupture of the abdominal aorta following extracorporeal shock-wave lithotripsy.

PMID- 9562288
TI  - Differences in stretch reflex responses of elbow flexor muscles during
      shortening, lengthening and isometric contractions.
AB  - Stretch reflexes were evoked in elbow flexor muscles undergoing three different
      muscle contractions, i.e. isotonic shortening (SHO) and lengthening (LEN), and
      isometric (ISO) contractions. The intermuscle relationships for the magnitude of
      the stretch reflex component in the eletromyographic (EMG) activities of two main
      elbow flexor muscles, i.e. the biceps brachii (BB) and the brachioradialis (BRD),
      were compared among the three types of contractions. The subjects were requested
      to move their forearms sinusoidally (0.1 Hz) against a constant pre-load between
      elbow joint angles of 10 degrees (0 degrees = full extension) and 80 degrees
      during SHO and LEN, and to keep an angle of 45 degrees during the ISO. The
      perturbations were applied at the elbow angle of 45 degrees in pseudo-random
      order. The EMG signals were rectified and averaged over a period of 100 ms before
      and 400 ms after the onset of the perturbation 40-50 times. From the ensemble
      averaged EMG waveform, the background activity (BGA), short (20-50 ms) and long
      latency (M2, 50-80, M3, 80-100 ms) reflex and voluntary activity (100-150 ms)
      components were measured. The results showed that both BGA and reflex EMG
      activity of the two elbow flexor muscles were markedly decreased during the
      lengthening contraction compared to the SHO and ISO contractions. Furthermore,
      the changes of reflex EMG components in the BRD muscle were more pronounced than
      those in the BB muscle, i.e. the ratios of M2 and M3 magnitudes between BRD and
      BB (BRD:BB) were significantly reduced during the LEN contractions. These results
      would suggest that the gain of long latency stretch reflex EMG activities in
      synergistic muscles might be modulated independently according to the model of
      muscle contraction.

PMID- 9562289
TI  - Exercise-induced hormone responses in girls at different stages of sexual
      maturation.
AB  - The dependence of exercise-induced hormone responses on sexual maturation was
      tested in a 3-year longitudinal experiment on 34 girls (aged 11-12 years at the
      beginning). Sexual maturation was evaluated by Tanners five-stage scale. Children
      cycled for 20-min at 60% maximal oxygen uptake once a year. Cortisol, insulin,
      growth hormone, beta-oestradiol, progesterone and testosterone concentrations in
      venous blood were determined by radioimmunoassay procedures. Basal concentrations
      of growth hormone increased and of cortisol decreased when breast stage III was
      reached. Reaching breast stage IV was associated with an increase in basal
      concentrations of beta-oestradiol, progesterone and testosterone. The exercise
      induced significant increases in concentrations of cortisol, growth hormone and
      beta-oestradiol and a decrease in insulin concentration. At breast stage III the
      increase in cortisol concentration was to a lower level [467 (SEM 42) vs 567 (SEM
      46)nmol x l(-1)] and growth hormone concentration to a higher level [29.4 (SEM
      0.5) vs 12.8 (SEM 0.4)ng x ml(-1)], while the fall in insulin concentration was
      less pronounced [postexercise level 10.6 (SEM 0.9) vs 7.8 (SEM 0.8)mU x l(-1)]
      than in stage II. The magnitude of the cortisol response was reduced in the last
      stage of breast development (+42.1% vs +55.5% at stage II, +66.2% at stage III,
      and +50.0% at stage IV). The magnitude of beta-oestradiol response was the lowest
      in breast stage IV (+15.8%) and the highest at stage V (+41.1%). The progesterone
      response became significant at stage IV and testosterone response at stage V. In
      conclusion, we found that reaching breast stage III was associated with altered
      responses of cortisol, insulin and growth hormone concentrations while the
      responses of the sex hormone concentrations became pronounced in the last stages
      of sexual maturation.

PMID- 9562290
TI  - Effect of exercise-induced acidosis on aldosterone secretion in men.
AB  - The present study was carried out to elucidate whether an exercise-induced
      increase in plasma hydrogen ion concentration influences aldosterone secretion.
      Six healthy men (aged 22-25 years) performed two intermittent exercise tests with
      and without drug administration. The intensities of these exercise tests were 40%
      maximal oxygen uptake (VO2max) and 90% VO2max, respectively. Administration of 2
      mg Dexamethasone and 50-mg Captopril caused an almost complete suppression of
      adrenocorticotropic hormone (ACTH) and an enhancement of the elevation in renin
      concentration during exercise, indicating successful inhibition of ACTH release
      and angiotensin II production during exercise. While the magnitude of the
      increase in aldosterone in the drug experiment was depressed compared with the
      control experiment, a significant increase in aldosterone concentration was
      observed at the end of the 90% VO2max exercise. Whilst the change in aldosterone
      concentration did not correlate with the change in plasma potassium
      concentration, there was a significant correlation between aldosterone and plasma
      hydrogen ion concentrations in the drug experiment. Since the correlation
      coefficient was low (r = 0.455), the biological meaning of this correlation
      should be further investigated. These results would suggest that an elevation of
      plasma hydrogen ion concentration induced by exercise per se appears to be
      related, at least in part, with increased aldosterone secretion, independent of
      the pituitary-adrenal axis, and the renin-angiotensin system.

PMID- 9562291
TI  - Plasma catecholamine and serum testosterone responses to four units of resistance
      exercise in young and adult male athletes.
AB  - The plasma noradrenaline (NA) and adrenaline (A) concentration responses of seven
      young male athletes [15 (SD 1) years] and seven adult male athletes [25 (SD 6)
      years] were investigated together with the serum testosterone (Tes) concentration
      responses in four different half-squatting exercises. The loads, number of
      repetitions, exercise intensity and recovery between the sets were manipulated
      such that different types of metabolic demand could be expected. However, the
      amount of work done was kept equal in each kind of exercise. After the most
      exhausting unit of exercise (E3; two sets of 30 repetitions with 50% of 1
      repetition maximum and with 2-min recovery between the sets) the plasma NA
      concentration was significantly lower in the younger than in the adult subjects
      [15.7 (SD 7.8) vs 32.7 (SD 13.2) nmol x l(-1), P < 0.05], while the A
      concentrations were similar. In the other three exercises no differences in the
      plasma catecholamine concentration responses among the groups were observed. The
      postexercise Tes concentrations, however, were significantly lower in the younger
      than in the adult subjects in every exercise unit. No correlations between the
      plasma catecholamine and serum Tes concentration responses were observed in any
      of the exercise units in either group. The results of the present study may
      suggest reduced sympathetic nervous activity in the younger subjects compared to
      the adults in response to exhausting resistance exercise. The results may also
      suggest that the catecholamines were less involved in eliciting an increase in
      Tes secretion in these resistance exercises.

PMID- 9562292
TI  - Ventilatory efficiency and exercise tolerance in 101 healthy volunteers.
AB  - The ventilatory equivalent for CO2 defines ventilatory efficiency largely
      independent of metabolism. An impairment of ventilatory efficiency may be caused
      by an increase in either anatomical or physiological dead space, the latter being
      the most important mechanism in the hyperpnoea of heart failure, pulmonary
      embolism, pulmonary hypertension and the former in restrictive lung disease.
      However, normal values for ventilatory efficiency have not yet been established.
      We investigated 101 (56 men) healthy volunteers, aged 16-75 years, measuring
      ventilation and gas exchange at rest (n = 64) and on exercise (modified Naughton
      protocol, n = 101). Age and sex dependent normal values for ventilatory
      efficiency at rest defined as the ratio ventilation:carbon dioxide output
      (VE:VCO2), exercise ventilatory efficiency during exercise, defined as the slope
      of the linear relationship between ventilation and carbon dioxide output (VE vs
      VCO2 slope), oxygen uptake at the anaerobic threshold and at maximum (VO2AT,
      VO2max, respectively) and breathing reserve were established. Ventilatory
      efficiency at rest was largely independent of age, but was smaller in the men
      than in the women [VE:VCO2 50.5 (SD 8.8) vs 57.6 (SD 12.6) P < 0.05]. Ventilatory
      efficiency during exercise declined significantly with age and was smaller in the
      men than in the women (men: (VE vs VCO2 slope = 0.13 x age + 19.9; women: VE vs
      VCO2 slope = 0.12 x age + 24.4). The VO2AT and VO2max were 23 (SD 5) and 39 (SD
      7) ml O2 x kg x min(-1) in the men and 18 (SD 4) and 32 (SD 7) in the women,
      respectively, and declined significantly with age. The VO2AT was reached at 58
      (SD 9)% VO2max. Breathing reserve at the end of exercise was 41% and was
      independent of sex and age. It was concluded from this study that ventilatory
      efficiency as well as peak oxygen uptake are age and sex dependent in adults.

PMID- 9562293
TI  - Effects of caffeine, ephedrine and their combination on time to exhaustion during
      high-intensity exercise.
AB  - This study investigated the effects of acute ingestion of caffeine (C), ephedrine
      (E) and their combination (C+E) on time to exhaustion during high-intensity
      exercise. Using a repeated-measures, double-blind design, eight male subjects
      exercised on a cycle ergometer at a power output that led to exhaustion after
      about 12.6 min during a placebo (P) control trial. They did this 1.5 h after
      ingesting either C (5 mg x kg[-1]), E (1 mg x kg[-1]), C+E, or P. Trials were
      separated by 1 week. Venous blood was sampled before and during exercise. The
      mean (SD) times to exhaustion were 12.6 (3.1) (P), 14.4 (4.1) (C), 15.0 (5.7) (E)
      and 17.5 (5.8) (C+E) min. Only the C+E treatment significantly increased time to
      exhaustion compared to P. Oxygen consumption (VO2), carbon dioxide production
      (VCO2), minute ventilation (VE) and the respiratory exchange ratio (RER) were
      similar during exercise for all trials. Heart rate during exercise was
      significantly increased for the C+E and C trials compared to P. Subjective
      ratings of perceived exertion during exercise were significantly lower after C+E
      compared to P. All treatments significantly increased lactate levels. Free fatty
      acid (FFA) levels were significantly increased by C ingestion. Glycerol levels
      were increased by C+E and C ingestion. Glucose levels were also higher with the
      drug treatments compared to P. Increased monamine availability after C+E
      treatment was suggested by measurements of catecholamines and dopamine. In
      conclusion, the combination of C+E significantly prolonged exercise time to
      exhaustion compared to P, while neither C nor E treatments alone significantly
      changed time to exhaustion. The improved performance was attributed to increased
      central nervous system stimulation.

PMID- 9562294
TI  - The effects of high-intensity intermittent exercise on the plasma concentrations
      of glutamine and organic acids.
AB  - Glutamine is an essential substrate for the proper functioning of cells of the
      immune system. Falls in plasma glutamine concentration after exercise may have
      deleterious consequences for immune cell function and render the individual more
      susceptible to infection. The purpose of the present study was to examine changes
      in plasma glutamine concentration (measured using a validated enzymatic
      spectrophotometric method) following an acute bout of intermittent high-intensity
      exercise. Eight well-trained male games players took part in the study. Subjects
      reported to the laboratory following an overnight fast and performed a 1-h cycle
      exercise task consisting of 20 1-min periods at 100% maximal O2 consumption
      (VO2max) each separated by 2 min of recovery at 30% VO2max. Venous blood samples
      were taken before exercise and at 5 min, 1 h, 2.5 h, 5 h and 24 h post-exercise.
      Glutamine was measured by enzymatic spectrophotometric determination of the
      ammonia concentration before and after treatment of the plasma with glutaminase
      (EC 3.5.1.2). Plasma glutamine concentration did not fall in the immediate post
      exercise period [pre-exercise 681 (23) microM compared with 663 (46) microM at 5
      min post-exercise, mean (SEM)], but fell to 572 (35) microM at 5 h post-exercise
      (P < 0.05 compared with pre-exercise). Plasma lactate concentration rose to 8.8
      (1.0) mM at the end of exercise and fell to 1.8 (0.4) mM at 1 h post-exercise,
      but plasma concentrations of free fatty acids and beta-hydroxybutyrate both rose
      substantially in the post-exercise period (to 240% and 400% of pre-exercise
      levels, respectively). The circulating leucocyte count increased significantly
      during exercise (P < 0.01), continued to increase in the hours following exercise
      and peaked at 2.5 h post-exercise (mainly due to a neutrophilia). The fall in the
      plasma glutamine concentration at 5 h post-exercise could be due to increased
      renal uptake of glutamine, which generally occurs in conditions of metabolic
      acidosis or due to a greater removal of glutamine from the plasma resulting from
      the elevated circulating leucocyte count.

PMID- 9562295
TI  - Heart rate and blood pressure responses to isometric exercise in young and older
      men.
AB  - The aim of this study was to examine the isometric endurance response and the
      heart rate and blood pressure responses to isometric exercise in two muscle
      groups in ten young (age 23-29 years) and seven older (age 54-59 years)
      physically active men with similar estimated forearm and thigh muscle masses.
      Isometric contractions were held until fatigue using the finger flexor muscles
      (handgrip) and with the quadriceps muscle (one-legged knee extension) at 20%,
      40%, and 60% of the maximal voluntary contraction (MVC). Heart rate and arterial
      pressure were related to the the individual's contraction times. The isometric
      endurance response was longer with handgrip than with one-legged knee extension,
      but no significant difference was observed between the age groups. The isometric
      endurance response averaged 542 (SEM 57), 153 (SEM 14), and 59 (SEM 5) s for the
      handgrip, and 276 (SEM 35), 94 (SEM 10) and 48 (SEM 5) s for the knee extension
      at the three MVC levels, respectively. Heart rate and blood pressure became
      higher during one-legged knee extension than during handgrip, and with increasing
      level of contraction. The older subjects had a lower heart rate and a higher
      blood pressure response than their younger counterparts, and the differences were
      more apparent at a higher force level. The results would indicate that increasing
      age is associated with an altered heart rate and blood pressure response to
      isometric exercise although it does not affect isometric endurance.

PMID- 9562296
TI  - Oxygen uptake does not increase linearly at high power outputs during incremental
      exercise test in humans.
AB  - A group of 12 healthy non-smoking men [mean age 22.3 (SD 1.1) years], performed
      an incremental exercise test. The test started at 30 W, followed by increases in
      power output (P) of 30 W every 3 min, until exhaustion. Blood samples were taken
      from an antecubital vein for determination of plasma concentration lactate [La
      ]pl and acid-base balance variables. Below the lactate threshold (LT) defined in
      this study as the highest P above which a sustained increase in [La-]pl was
      observed (at least 0.5 mmol x l[-1] within 3 min), the pulmonary oxygen uptake
      (VO2) measured breath-by-breath, showed a linear relationship with P. However, at
      P above LT [in this study 135 (SD 30) W] there was an additional accumulating
      increase in VO2 above that expected from the increase in P alone. The magnitude
      of this effect was illustrated by the difference in the final P observed at
      maximal oxygen uptake (VO2max) during the incremental exercise test (Pmax,obs at
      VO2max) and the expected power output at VO2max(Pmax,exp at VO2max) predicted
      from the linear VO2-P relationship derived from the data collected below LT. The
      Pmax,obs at VO2max amounting to 270 (SD 19) W was 65.1 (SD 35) W (19%) lower (P <
      0.01) than the Pmax,exp at VO2max. The mean value of VO2max reached at Pmax,obs
      amounted to 3555 (SD 226) ml x min(-1) which was 572 (SD 269) ml x min(-1) higher
      (P < 0.01) than the VO2 expected at this P, calculated from the linear
      relationship between VO2 and P derived from the data collected below LT. This
      fall in locomotory efficiency expressed by the additional increase in VO2,
      amounting to 572 (SD 269) ml O2 x min(-1), was accompanied by a significant
      increase in [La-]pl amounting to 7.04 (SD 2.2) mmol x l(-1), a significant
      increase in blood hydrogen ion concentration ([H+]b) to 7.4 (SD 3) nmol x l(-1)
      and a significant fall in blood bicarbonate concentration to 5.78 (SD 1.7) mmol x
      l(-1), in relation to the values measured at the P of the LT. We also correlated
      the individual values of the additional VO2 with the increases (delta) in
      variables [La-]pl and delta[H+]b. The delta values for [La-]pl and delta[H+]b
      were expressed as the differences between values reached at the Pmax,obs at
      VO2max and the values at LT. No significant correlations between the additional
      VO2 and delta[La-]pl on [H+]b were found. In conclusion, when performing an
      incremental exercise test, exceeding P corresponding to LT was accompanied by a
      significant additional increase in VO2 above that expected from the linear
      relationship between VO2 and P occurring at lower P. However, the magnitude of
      the additional increase in VO2 did not correlate with the magnitude of the
      increases in [La-]pl and [H+]b reached in the final stages of the incremental
      test.

PMID- 9562297
TI  - Effects of training for two ball games on the saliva response of adrenocortical
      hormones to exercise in elite sportswomen.
AB  - In a group of 20 elite female handball or volleyball players, an evaluation was
      made of the response to a 4-month training period of cortisol, androstenedione
      and dehydroepiandrosterone in the saliva. At the beginning of the training
      programme (W1) and at the 7th (W7) and 16th weeks (W16), hormone concentrations
      were measured on awakening (8 a.m.; resting samples), and also before (t0) and at
      the end (t120) of a 2-h exercise session (simulated match) which took place at 6
      p.m. The training programme increased the concentrations of adrenal androgens in
      the saliva at rest (P < 0.05) for both groups of subjects, with no change being
      noted in cortisol concentrations. In contrast, amongst the volleyball players,
      stressful stimuli produced by an increase in the amount of training did not
      affect adrenocortical metabolism during exercise. Indeed, a simulated volleyball
      match resulted in a decrease in salivary cortisol (P < 0.05) and androgen
      concentrations (P < 0.05) without regard for the week chosen for the test
      investigations. In contrast, a simulated handball match caused an increase in
      cortisol concentrations at W1 only (P < 0.05), with no change in the adrenal
      androgens concentration in any week of the training programme. The regulators of
      these hormones during a period of exercise and during the course of a training
      programme would seem to be different.

PMID- 9562298
TI  - Plasma volume in acute hypoxia: comparison of a carbon monoxide rebreathing
      method and dye dilution with Evans' blue.
AB  - Exposure to acute hypoxia is associated with changes in body fluid homeostasis
      and plasma volume (PV). This study compared a dye dilution technique using Evans'
      blue (PV[Evans']) with a carbon monoxide (CO) rebreathing method (PV[CO]) for
      measurements of PV in ten normal subjects at sea level and again 24 h after rapid
      passive ascent to high altitude (4,350 m). Hypobaric hypoxia decreased arterial
      oxygen saturation to 79 (74-83)% (mean with 95% confidence intervals). The
      PV(Evans') remained unchanged from 3.49 (3.30-3.68) l at sea level to 3.46 (3.24
      3.68) l at high altitude. In contrast PV(CO) decreased from 3.39 (3.17-3.61) l at
      sea level to 3.04 (2.75-3.33) l at high altitude (P < 0.05). Compared with sea
      level, this resulted in an increase of the mean bias between the two methods
      [from 0.11 (-0.05-0.27) l at sea level to 0.43 (0.26-0.60) l at high altitude] so
      that the ratio between PV(Evans') and PV(CO) increased from 1.04 (0.99-1.09) at
      sea level to 1.15 (1.06-1.24) at high altitude (P < 0.05). In conclusion, the two
      methods were not interchangeable as measures of hypoxia-induced changes in PV.
      The mechanism responsible for the bias remains unknown, but it is suggested that
      the results may reflect a redistribution of albumin caused by the combined
      effects in hypoxia of both an increased capillary permeability to albumin and a
      decrease in PV. As a result, the small perivascular compartment of albumin beyond
      the endothelium may increase without changes in the overall albumin distribution
      volume.

PMID- 9562299
TI  - Effects of contraction duration on low-frequency fatigue in voluntary and
      electrically induced exercise of quadriceps muscle in humans.
AB  - The aims of this study were to investigate if low-frequency fatigue (LFF)
      dependent on the duration of repeated muscle contractions and to compare LFF in
      voluntary and electrically induced exercise. Male subjects performed three 9-min
      periods of repeated isometric knee extensions at 40% maximal voluntary
      contraction with contraction plus relaxation periods of 30 plus 60 s, 15 plus 30
      s and 5 plus 10 s in protocols 1, 2 and 3, respectively. The same exercise
      protocols were repeated using feedback-controlled electrical stimulation at 40%
      maximal tetanic torque. Before and 15 min after each exercise period, knee
      extension torque at 1, 7, 10, 15, 20, 50 and 100 Hz was assessed. During
      voluntary exercise, electromyogram root mean square (EMGrms) of the vastus
      lateralis muscle was evaluated. The 20-Hz torque:100-Hz torque (20:100 Hz torque)
      ratio was reduced more after electrically induced than after voluntary exercise
      (P < 0.05). During electrically induced exercise, the decrease in 20:100 Hz
      torque ratio was gradually (P < 0.05) reduced as the individual contractions
      shortened. During voluntary exercise, the decrease in 20:100 Hz torque ratio and
      the increase in EMGrms were greater in protocol 1 (P < 0.01) than in protocols 2
      and 3, which did not differ from each other. In conclusion, our results showed
      that LFF is dependent on the duration of individual muscle contractions during
      repetitive isometric exercise and that the electrically induced exercise produced
      a more pronounced LFF compared to voluntary exercise of submaximal intensity. It
      is suggested that compensatory recruitment of faster-contracting motor units is
      an additional factor affecting the severity of LFF during voluntary exercise.

PMID- 9562300
TI  - Cerebral cortical blood flow in rabbits during parabolic flights (hypergravity
      and microgravity).
AB  - We studied the effect of gravity on cerebral cortical blood flow (CBF), mean
      arterial blood pressure (BPa) and heart rate in six rabbits exposed to parabolic
      flights. The CBF was obtained using a laser-Doppler probe fixed on to a cranial
      window. Before weightlessness, the animals were exposed to chest-to-back directed
      acceleration (1.8-2.0 g). The CBF values were expressed as a percentage of CBFo
      (mean CBF during 60 s before the 1st parabola). Propranolol (1 mg x kg[-1] i.v.)
      was given after the 11th parabola and pentobarbital (12-15 mg x kg[-1] i.v.)
      after the 16th parabola. Before the administration of the drugs, CBF increased (P
      < 0.01) during hypergravity [i.e. maximal CBF 151 (SD 64)% CBFo. Simultaneously
      BPa increased [maximal BPa, 119 (SD 11) mmHg (P < 0.01)]. At the onset of
      weightlessness, CBF and BPa reached maximal values [194 (SD 96)% CBFo (P < 0.01)
      and 127 (SD 19) mmHg, (P < 0.01) respectively]. The microgravity-induced increase
      in CBF was transient since CBF returned to its baseline value after 8 (SD 2) s of
      microgravity. After propranolol administration, CBF was not statistically
      different during hypergravity but an elevation of CBF was still observed in
      weightlessness. The increases in CBF and BPa also persisted during weightlessness
      after pentobarbital administration. These data would indicate that CBF of
      nonanesthetized rabbits increases during the first seconds of weightlessness and
      demonstrate the involvement of rapid active regulatory mechanisms since CBF
      returned to control values within 8 (SD 2) s. We concluded that this elevation in
      blood flow was not related to stress because it persisted after the
      administration of propranolol and pentobarbital.

PMID- 9562301
TI  - The neuroprotective effects of the recombinant interleukin-1 receptor antagonist
      rhIL-1ra after excitotoxic stimulation with kainic acid and its relationship to
      the amyloid precursor protein gene.
AB  - The cytokine interleukin-1 (IL-1) and its endogenous antagonist (IL-1ra) have
      important functions in the central nervous system. Recent experimental
      observations have suggested that recombinant IL-1RA (rhIL-1ra) has
      neuroprotective properties in ischaemia, excitotoxicity, and trauma. We wished to
      see what effect rhIL-1ra had on kainic acid-induced neuronal death and to
      investigate how this might relate to changes in expression of the amyloid
      precursor protein gene (APP) and glial fibrillary acid protein (GFAP) using in
      situ hybridization. Wistar rats were treated by intracerebroventricular
      administration with rhIL-1ra at doses of 10, 20 and 40 microg given 10 min before
      and 10 min after intraperitoneal kainic acid 10 mg/kg. Behaviour was measured
      and, after 10 days, the brains were removed for histology and in situ
      hybridization. There were no anticonvulsant effects on kainic acid-induced wet
      dog shakes or limbic motor seizures. There were no differences in the effects of
      rhIL-1ra at all doses tested on hippocampal temperature, blood pressure, blood
      gases, pH, and glucose in comparison to control. With rhIL-1ra 10 microg given
      twice, there was significant protection of neurons in the CA1 and CA3 field of
      the hippocampus and dorsal thalamus, but not in the primary olfactory cortex
      amygdaloid region. Small, but insignificant, neuroprotective effects were
      observed in the same anatomical regions with a dose of 20 microg given twice, and
      no neuroprotective effects were observed with 40 microg. The enhanced neuronal
      survival in CA1, CA3 and the dorsal thalamus was associated with preservation of
      APP 695 mRNA (neuronal form) and lack of stimulation of APP 770 (glial form) and
      GFAP messages. Where there was no neuroprotection APP 695 mRNA was reduced and
      stimulation of both APP 770 and GFAP mRNAs was observed. In conclusion, rhIL-1ra
      has dose- and region-dependent effects on neuronal survival after kainic acid and
      prevents damage-induced changes in APP and GFAP mRNAs.

PMID- 9562302
TI  - Granule cell dispersion is correlated with early epileptic events in human
      temporal lobe epilepsy.
AB  - Granule cell dispersion (GCD) into the dentate gyrus (DG) molecular layer was
      observed in hippocampal specimens in 10 out of 22 cases of human non-lesional
      temporal lobe epilepsy (TLE) and was associated with hippocampal sclerosis (HS).
      The presence of GCD was significantly linked to events of epileptic nature
      arising during the first 4 years of life but not with the durations of epilepsy,
      nor the number of seizures. Dispersion could be induced by seizure-linked
      structural plasticity occurring during a specific early permissive period.

PMID- 9562303
TI  - Serum autoantibodies to neurofilament proteins in sporadic amyotrophic lateral
      sclerosis.
AB  - Anti-neurofilament (NF) autoantibodies were searched for by enzyme-linked
      immunosorbent assays (ELISA) in the serum from 85 sporadic amyotrophic lateral
      sclerosis (ALS) patients, 98 healthy controls and 79 patients with unrelated
      immunological diseases (Guillain-Barre syndrome, myasthenia gravis and multiple
      sclerosis). ELISA cutoff value was determined as mean control levels +2 SD and it
      corresponded to a specificity of 94%. Such high level antibodies were detected in
      24.7% of ALS patients contrasting with 12.6% of neurological controls (P<0.05)
      and only 6.1% of healthy subjects (P<5.10[-4]). In ALS, anti-NF antibodies were
      significantly associated with a slow evolution, as measured by the mean time
      spent in the initial functional states. They did not relate with age, sex and
      clinical form. The predominant isotype of the anti-NF antibodies was IgM lambda
      by ELISA. In contrast to negative sera, indirect immunohistochemical studies
      demonstrated that most sera positive for anti-NF antibodies reacted with axons
      with predominant isotypes restricted to IgM lambda. By using Western blotting,
      small amounts of serum monoclonal IgM were found with a high frequency in anti-NF
      antibody-positive patients. These results suggest the possible involvement of
      anti-NF antibodies in an autoimmune process in a subgroup of ALS patients.

PMID- 9562304
TI  - Decrease in benzodiazepine receptor binding in the brains of adult patients with
      Rett syndrome.
AB  - To evaluate benzodiazepine (BZD) receptor binding in the brains of patients with
      the Rett syndrome (RS), three Japanese adult females with stage IV RS were
      evaluated by single-photon emission computed tomography (SPECT) using [123I]
      iomazenil. The iomazenil images were obtained 20 min and 3 h post-injection and
      analyzed for BZD receptor binding. The binding potential (BP) for the BZD
      receptor was significantly decreased in the fronto-temporal cortex of the RS
      patients (P<0.05). They also exhibited a decreased BP ratio (BP of each region/BP
      of cerebellum) in the fronto-temporal (P<0.01), occipital and parietal (P<0.05)
      cortical gray matter as compared with the ratios observed in five healthy male
      volunteers. In one RS patient, a marked decrease of iomazenil binding was
      observed in the late SPECT images, while the early SPECT images showed well
      preserved cerebral perfusion. This difference strongly suggests that changes in
      the BZD receptor in RS are primary abnormality, not secondary to a decrease in
      cerebral blood flow.

PMID- 9562305
TI  - Discrimination of facial identity and of emotions in Alzheimer's disease.
AB  - OBJECTIVE: To investigate processing of human faces identity and of emotional
      expressions in patients with Alzheimer's Disease (AD). BACKGROUND: Mechanisms
      responsible for discriminating facial identity may be dissociated from those
      involved in discriminating facial expressions. Patients with prosopagnosia often
      have preserved capacities for processing emotional facial expressions and
      occasionally, patients with focal lesions may recognize human faces without being
      able to recognize their facial expression. Such a dissociation has not been
      clearly shown in groups of AD patients. METHODS: Thirty-one probable AD patients
      and 14 control subjects were administered tasks of discrimination of faces and of
      emotions. RESULTS: AD patients were significantly impaired in discriminating
      facial identities and in naming and pointing to named emotions, but were
      comparable to controls in discriminating facial expressions of emotion. The
      deficits of facial discrimination and of identification of emotions were, on the
      whole, correlated with the MMS and Raven scores. Discrimination of emotions was
      not correlated to either test, suggesting that this ability is based on cognitive
      processes different from those underlying the MMS and the PM47. CONCLUSIONS: This
      dissociation implies two separate systems, one dedicated to discrimination of
      facial identities and the other to discrimination of emotions. This is compatible
      with the modular organization of cognitive deficits in AD and may explain the
      well known experience that nonverbal communication often remains effective even
      in patients with severe dementia.

PMID- 9562306
TI  - Aggregation of amyloid beta-protein as function of age and apolipoprotein E in
      normal and Alzheimer's serum.
AB  - We compared the effect of serum from (a) 26 Alzheimer's disease (AD) patients and
      22 age-matched non-demented controls (CO) with apolipoprotein E 4/4, 3/3 or 3/2
      phenotypes, and (b) 17 normal young (aged 15-41 years) and 21 normal elderly
      (aged 64-83 years) people on in vitro aggregation of synthetic amyloid beta
      protein (A beta) 1-40 by Thioflavin T fluorescence spectroscopy. A beta 1-40
      aggregation in presence of serum from the normal elderly group was significantly
      higher as compared to the normal young group (correlation coefficient between age
      and A beta aggregation=0.73). However, no difference in A beta aggregation was
      observed in the presence of serum from AD patients and non-demented controls.
      There was a positive correlation between serum apo E concentrations and A beta
      aggregation, while there was no significant difference between different apo E
      phenotypes. The correlation coefficient in the AD 4/4 (0.65) was higher than the
      CO 4/4 group (0.04), while it was lower in the AD 3/3 group (-0.12) than in the
      CO 3/3 (0.39) group. These results suggest that the apo E4 allele alone may not
      be responsible for A beta fibril formation in AD; other factors may be involved
      in increasing risk for AD pathogenesis in those having the apo E4 allele. The
      severity of dementia and serum albumin levels also did not correlate with A beta
      aggregation. We propose that the age of an individual may be an important factor
      in determining the degree of A beta aggregation/fibrillization, and that
      mechanism of sequestration of A beta in serum may not be defective in AD.

PMID- 9562307
TI  - Localization analysis of neuronal activities in benign rolandic epilepsy using
      magnetoencephalography.
AB  - Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical
      syndrome characterized by partial sensorimotor seizures with centrotemporal
      spikes. We report a detailed localization analysis of spontaneous magnetic brain
      activities in seven BECRS patients using magnetoencephalography (MEG). All
      patients had BECRS diagnosis with typical seizures and electroencephalographic
      findings and five patients had minor psychomotor deficits. MEG was recorded over
      both parieto-temporal regions using a 2x37-channel biomagnetic system. The
      collected data were digitally bandpass-filtered (2-6, 14-30, or 1-70 Hz) to
      analyze slow- and fast-wave magnetic activities and rolandic spikes. Slow-wave
      activity was increased in four hemispheres of three patients. Increased fast-wave
      activity was found in all five patients with minor neuropsychological deficits.
      The presence of increased fast-wave magnetic brain activity appeared to cause
      functional anomalies in the higher brain function processes. In the spike
      analysis, the dipoles of rolandic spikes which constantly manifested anterior
      positivity in direction were concentrated in the superior rolandic region in four
      cases and the inferior rolandic region in three cases. The localizations of
      increased slow- and fast-wave activities were identical with those of the spikes.
      The seizure profiles were frequently characterized by the spike locations. Source
      localizations of the focal brain activities and rolandic spikes by MEG will
      contribute to the different diagnosis and pathophysiological elucidation of
      BECRS.

PMID- 9562308
TI  - Cerebrospinal fluid complement activation in neurological diseases.
AB  - Laser nephelometry (LN) is a rapid and very sensitive method for simultaneous
      determination of albumin, immunoglobulins, C3c and C4 in diluted serum and paired
      cerebrospinal fluid (CSF) samples. It is very useful in routine analyses.
      Determination of C3c and C4 covers classical as well as alternative pathways of
      complement activation. In CSF, they are mostly derived from and related to serum
      values. Under physiological conditions, the addition of intrathecal C4 synthesis
      is likely. The incidence of complement activation within CSF is also influenced
      by the method of choice (native molecules, activation products and complexes,
      inhibitors) and the mode of interpretation of results according to the functional
      state of the blood-brain barrier (BBB). Calculation of indexes and the modified
      Reiber's graph method are valid means of detection of complement activation
      within CSF. Complement activation within CSF was confirmed in 36% (111/302) of
      neurological patients examined; in 55% (48/87) of patients with inflammatory and
      demyelinating diseases, in 40% (37/94) of patients with CNS infections and
      complications, in 33% (4/12) of patients with motor neuron diseases, in 27%
      (11/40) of patients with spinal cord compression and sequelae, in 25% (8/32) of
      patients with neoplastic disease, and in 17% (6/37) of patients with
      cerebrovascular accidents.

PMID- 9562309
TI  - Mechanism of short-term memory and repetition in conduction aphasia and related
      cognitive disorders: a neuropsychological, audiological and neuroimaging study.
AB  - To evaluate the role of the sub-cortical white matter and cortical areas of the
      supramarginal gyrus in short-term memory impairment (shortened digit or letter
      span) and repetition difficulty, four patients with conduction aphasia and
      impaired short-term memory and two patients with only short-term memory
      impairment were given digit span, letter span, speech audiometry and dichotic
      listening tests. The results showed that in most of the patients letter span was
      inferior to digit span and that bilateral ear suppression in the dichotic
      listening test was observed in two patients with a lesion in the inferior part of
      the supramarginal gyrus, suggesting that what was affected was phonological
      information and that the supramarginal gyrus was the storage site. The overlapped
      lesion of conduction aphasia patients with short-term memory impairment was the
      periventricular white matter at the upper to middle part of the trigone, while
      patients with only short-term memory impairment had a lesion in the inferior
      supramarginal gyrus in common. Thus, damage to the periventricular white matter
      at the trigone may yield the phonemic paraphasia characteristic of conduction
      aphasia, while damage to the inferior part of the supramarginal gyrus may result
      in the impairment of short-term memory. We believe that as a part of the
      mechanisms of short-term memory and repetition, phonological information is
      processed in the primary auditory cortex and goes through the periventricular
      white matter to the inferior part of the supramarginal gyrus and is temporarily
      stored there.

PMID- 9562310
TI  - Cerebrospinal fluid interleukin 6 in amyotrophic lateral sclerosis: immunological
      parameter and comparison with inflammatory and non-inflammatory central nervous
      system diseases.
AB  - We assayed IL-6 in 105 cerebrospinal fluid (CSF) samples from patients with ALS,
      MS, HTLV-1 associated myelopathy (HAM), and controls. There was considerable
      overlap in IL-6 levels in all patient groups. The mean IL-6 in 27 patients with
      ALS was significantly higher than in 21 patients in the other neurological
      disease (OND) group (P=0.0075). There were no significant differences in MS or
      HAM and the OND control group. Overall, CSF IL-6 correlated with protein
      concentration but not with percentage IgG or IgG-albumin index. Patients with CSF
      oligoclonal bands were no more likely to have detectable IL-6 than patients
      without oligoclonal bands. Similarly, IL-6 did not correlate with clinical
      disease activity in MS when subgroups of patients were compared or when an
      individual patient was followed over time. The elevated IL-6 in ALS may reflect
      an ongoing humoral immune response, or IL-6 may be non-specifically expressed in
      these patients as a putative neurotrophic factor in response to nerve cell
      degeneration.

PMID- 9562312
TI  - Early-onset multisystem degeneration with central motor, autonomic and optic
      nerve disturbances: unusual Riley-Day syndrome or new clinical entity?
AB  - We report a 21-year-old woman presenting with a slowly progressive tetraparesis,
      optic nerve atrophy on both sides, and autonomic disturbances since early
      childhood. The patient has been carefully followed up for 5 years with clinical
      and ancillary investigations. The results and the time course strongly suggest an
      underlying degenerative syndrome affecting parts of three major systems:
      autonomic, motor and visual. Some symptoms resemble familial dysautonomia (FD,
      Riley-Day syndrome), however, hallmarks of FD, such as absence of fungiform
      papillae of the tongue, abnormal reaction on intradermal histamine injection,
      absent tendon reflexes, are missing, and central motor disturbances have not been
      described in FD. We consider this syndrome a slowly progressive multisystemic
      degeneration with two unusual hitherto unreported features: the combination of
      affected systems (autonomic and motor systems, optic nerves), and the early
      onset.

PMID- 9562311
TI  - Risk factors and antiplatelet therapy in TIA and stroke patients.
AB  - Antiplatelet treatment is well established in the secondary prevention of
      ischemic cerebrovascular events. The reasons for the occurrence of stroke, even
      though the patient receives drug treatment, have remained unclear. We performed a
      subgroup analysis of the European Stroke Prevention Study (ESPS 1) to investigate
      the efficacy of treatment in patients with different cardiovascular risk factors.
      The ESPS 1 recruited 1306 patients with TIA, RIND or stroke in one single center
      of Kuopio in Finland. The patients were treated with aspirin 990
      mg/day+dipyridamole 225 mg/day or placebo for 2 years or until an endpoint. The
      endpoints were stroke or death from any cause. The risk factors for endpoints
      were analyzed by Cox univariate regression analyses. The effect of a single risk
      factor on the efficacy of antiplatelet therapy was analyzed by Cox proportional
      hazards model in subgroups according to the significant risk factors found in the
      univariate analysis. The efficacy of treatment was statistically significant in
      all subgroups except diabetics and current smokers for the stroke endpoint. When
      the combined endpoint of stroke or death was used, the treatment failed also to
      show statistical significance in patients with coronary heart disease. This lack
      of efficacy might be due to the small sample size. The efficacy of treatment was
      significantly better in TIA patients than in stroke patients when analyzed with
      stroke as an end point. This study provides strong evidence that the
      effectiveness of antiplatelet treatment in ischemic stroke and TIA patients is
      independent of most cardiovascular risk factors. Furthermore, all patients with
      TIA and ischemic stroke should receive secondary prevention regardless of whether
      or not there are risk factors.

PMID- 9562313
TI  - A gliotoxic factor and multiple sclerosis.
AB  - The pathogenesis of multiple sclerosis (MS) is unknown. Searching for possible
      toxic factors, it was found that 3-day exposure to heat-treated cerebrospinal
      fluid (CSF) from MS patients caused apoptotic death of astrocytes and
      oligodendrocytes, but not fibroblasts, myoblasts, Schwann cells, endothelial
      cells and neurons, in vitro. CSFs from other inflammatory or non-inflammatory
      neurological diseases showed no toxicity. Exposure of these glial cells to
      partially purified MS CSF produced DNA fragmentation, apoptotic bodies, chromatin
      condensation, cell shrinkage, and changes in the levels of known cytokines. A
      cytotoxic factor, called gliotoxin, was characterized chromatographically as a
      stable 17-kDa glycoprotein. Since this protein is highly cytotoxic for astrocytes
      and oligodendrocytes, it may represent an initial pathogenic factor, leading to
      the neuropathological features of MS, such as blood-brain barrier involvement and
      demyelination.

PMID- 9562314
TI  - Motor evoked potential is useful for monitoring the effect of collar therapy in
      cervical spondylotic myelopathy.
AB  - Motor and somatosensory evoked potential changes are reported in 20 patients with
      cervical spondylotic myelopathy following 6 and 12 weeks of collar therapy. The
      age of the patients ranged between 35 and 69 years and one of them was a female.
      Walking difficulty was present in 18 and their leg weakness ranged between grade
      2 and 4 on the 0-5 MRC (Medical Research Council) scale. Joint position sense was
      impaired in 14 patients. Central motor conduction time to tibialis anterior (CMCT
      TA) was prolonged in 18 patients (30 sides) and tibial somatosensory conduction
      time was abnormal in seven patients (11 sides), which was unrecordable in four
      (seven sides). Nineteen patients were followed up for 6 weeks and 10 for 12 weeks
      of collar therapy. One Nurick's grade improvement occurred in 12 and two grades
      in three patients at 6 weeks. The CMCT improvement was noted in 15 patients (25
      sides) which was associated with clinical improvement in 12 patients. At 3
      months, further clinical improvement occurred in four patients whereas CMCT
      improved in six (nine sides) out of 10 patients followed up. At 6 weeks follow
      up, tibial CSCT improved in 11 patients (17 sides) which correlated with
      improvement in sensations in seven patients. At 12 weeks further improvement in
      tibial CSCT was noted in two patients only (two sides). Central motor conduction
      time was more sensitive compared to CSCT for the evaluation of spondylotic
      myelopathy and the improvement was more pronounced at 6 compared to 12 weeks
      after collar therapy.

PMID- 9562315
TI  - Foramen magnum syndrome caused by atlanto-occipital assimilation.
AB  - Atlanto-occipital assimilation is one of the most common congenital anomalies of
      the craniovertebral junction, and it usually is asymptomatic. We report a case of
      this malformation with unusual neurological symptoms which correlate with
      radiological findings. The anomaly caused the so-called foramen magnum syndrome,
      which was difficult to localize with neurological examination. The patient also
      had atlanto-axial dislocation, which was thought to enhance the symptoms with
      change of head/neck position.

PMID- 9562316
TI  - Nasal administration of multiple antigens suppresses experimental autoimmune
      myasthenia gravis, encephalomyelitis and neuritis.
AB  - Oral tolerization with acetylcholine receptor (AChR) and myelin basic protein
      (MBP) prior to immunization with AChR+MBP+ complete Freund's adjuvant (CFA)
      alleviated clinical signs of experimental autoimmune myasthenia gravis
      (EAMG)+experimental allergic encephalomyelitis (EAE) and AChR- or MBP-specific T
      and B cell responses. Tolerance induced via the nasal route needs much less
      tolerogen and may still be as effective as oral tolerance induction. We now
      immunized Lewis rats with AChR+MBP+bovine peripheral nerve myelin (BPM)+CFA,
      which resulted in a multiphasic clinical picture with a combination of clinical
      signs of the EAMG+EAE+experimental allergic neuritis (EAN), accompanied by
      massive macrophage infiltrations in sections of muscle, spinal cord and sciatic
      nerve, and strong T and B cell responses to AChR, MBP and BPM in lymphoid organs.
      Nasal administration of microg doses of AChR+MBP+BPM prior to immunization with a
      mixture of these antigens+CFA effectively suppressed the incidence and severity
      of clinical disease, reduced macrophage infiltrations in sections of muscle,
      spinal cord and sciatic nerve, and down-regulated autoreactive T cell responses
      to the three antigens in lymphoid organs. Numbers of AChR-, MBP-, BPM-reactive
      Th1 type of cytokine interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha
      mRNA expression in lymph node cells were markedly suppressed, while transforming
      growth factor-beta (TGF-beta) mRNA expression was upregulated from nasally
      tolerized rats, suggesting an active suppression mechanism may act partly in the
      induction of tolerance. The results implicate the possibility to establish
      multiple autoantigen-based vaccination for the prevention of autoimmune diseases
      in humans.

PMID- 9562317
TI  - Glial cells production of inflammatory mediators induced by Streptococcus
      pneumoniae: inhibition by pentoxifylline, low-molecular-weight heparin and
      dexamethasone.
AB  - Exposure of primary rat glial cells to heat inactivated Streptococcus pneumoniae,
      induced dose-dependent production of tumor necrosis factor alpha (TNF alpha),
      nitric oxide (NO) and prostaglandin E2 (PGE2). Concomitant addition of the
      bacterium and the synthetic glucocorticoid dexamethasone resulted in complete
      suppression of TNF alpha, NO and PGE2 production. Pentoxifylline, a
      phosphodiesterase inhibitor completely blocked TNF alpha secretion, whereas NO
      and PGE2 were not affected. Low-molecular-weight heparin enoxaparin caused 25-64%
      inhibition in TNF alpha production, up to 30% inhibition of NO secretion and a
      10% reduction in PGE2. Thus, Streptococcus pneumoniae, the pathogen most commonly
      associated with meningitis in the Western world can be added to the list of
      agents causing direct stimulation of glial cells. Pentoxifylline and enoxaparin
      in addition to dexamethasone may limit the central nervous system local
      inflammatory responses and could improve the effort towards reducing the dismal
      outcome of patients with pneumococcal meningitis.

PMID- 9562318
TI  - Delayed Wallerian degeneration and increased neurofilament phosphorylation in
      sciatic nerves of rats with streptozocin-induced diabetes.
AB  - It is known that Wallerian degeneration (WD) is prerequisite for nerve
      regeneration, which is impaired in experimental diabetic rats. To elucidate the
      effect of hyperglycemia on WD, we studied the time course of WD after axotomy in
      streptozocin-diabetic (DM) and control rats. Sciatic nerves were removed at
      several time points after axotomy (days 0-24). Morphometric analysis indicated
      that WD was delayed in DM throughout experimental period. Quantitative
      immunohistochemical analysis showed that the early recruitment of macrophage did
      not differ between the two groups, although its late recruitment was
      significantly decreased in DM at 15 and 24 days post-axotomy, which suggested
      that the macrophage-associated process did not contribute to delayed WD in
      diabetes. Immunoblot analysis showed a delay in the degradation of neurofilaments
      (NFs) in DM during WD. Phosphorylated NFs detected by SMI31 were more recognized
      in DM, while the opposite was true for unphosphorylated NFs detected by SMI32.
      Since it is known that the sensitivity of NF to calpain-mediated proteolysis is
      modulated by its carboxyl-terminal phosphorylation state and phosphorylated NFs
      are resistant to calpains, we concluded that abnormal NF phosphorylation state in
      diabetes could be one of the mechanisms by which axonal degeneration was delayed.

PMID- 9562319
TI  - Effect of amino acid ergot alkaloids on glutamate transport via human glutamate
      transporter hGluT-1.
AB  - Effect of amino acid ergot alkaloids on glutamate transport via the human
      glutamate transporter (hGluT-1) was investigated using hGluT-HeLaS3 cells, which
      stably expressed high levels of hGluT-1. Ergotamine enhanced the glutamate uptake
      of hGluT-HeLaS3 cells in a concentration-dependent manner, increasing the initial
      velocity of glutamate uptake by 1.45 times at 10 microM. Other amino acid
      alkaloids, bromocriptine and dihydroergotamine, also augmented glutamate uptake,
      whereas amine alkaloids, ergonovine or lisuride did not influence glutamate
      uptake. The accelerating effect required a preincubation longer than 5 min.
      Kinetic studies on hGluT-1 revealed that ergot alkaloids decreased a Michaelis
      constant (Km) for glutamate with unchanged maximum velocity. The effect of
      bromocriptine was not mediated by dopamine D1 or D2 receptors, and was
      independent of its antioxidant action. Amino acid ergot alkaloids may serve as a
      prototype for agents that regulate glutamate transporters. These results may be
      useful in exploring new agents for neurological diseases associated with
      glutamatergic neurotoxicity.

PMID- 9562320
TI  - Neurological aspects of eclampsia.
AB  - Eclampsia accounts for a third of maternal mortality in developing countries. The
      neurological manifestations of eclampsia consist of seizures and alteration of
      sensorium or coma on a background of pre-eclampsia. Occasionally there can be
      focal neurological deficits too. Recent studies with CT scan and MRI have
      demonstrated the presence of cerebral edema and/or cerebral hemorrhage in
      eclampsia. EEG in patients with eclampsia has revealed evidence of diffuse
      cerebral dysfunction (delta waves) and epileptiform transients (spikes or sharp
      waves). There is also evidence of extensive vasculopathy within the brain
      parenchyma. A variety of mechanisms have been suggested to explain these changes,
      the most important being failure of autoregulation of cerebral blood flow that
      leads to cerebral edema and hemorrhage. There is considerable controversy
      regarding the treatment of seizures in eclampsia. Recent studies have shown that
      magnesium sulfate is superior to phenytoin or diazepam in the treatment of
      eclamptic seizures and prevention of eclamptic seizures in women with pre
      eclampsia.

PMID- 9562322
TI  - Longitudinal follow-up of cardiovascular reflex tests in multiple sclerosis.
AB  - Several studies have shown various degrees of autonomic dysfunction in patients
      with multiple sclerosis. Longitudinal follow-up studies are remarkably scarce up
      to now. We assessed autonomic dysfunction twice with an interval of 1 year in 20
      relapsing remitting and 26 secondary progressive MS-patients. Autonomic function
      was assessed by the heart rate response during deep breathing, standing up and
      Valsalva manoeuvre. Only the maximum change in heart rate after standing up (in
      ms and beats/min) and the Max/Min ratio after standing up showed significant
      worsening over 1 year. The changes in EDSS scores also documented gradual
      deterioration of the neurological condition over the study period. We conclude
      that there is progression of autonomic dysfunction in MS over 1 year and that
      this could correlate with progression in clinical disability.

PMID- 9562321
TI  - Acute optic neuritis: combined immunological markers and magnetic resonance
      imaging predict subsequent development of multiple sclerosis. The Optic Neuritis
      Study Group.
AB  - The diagnostic significance of intrathecally synthesized IgG and virus-specific
      antibodies to measles, rubella and varicella-zoster (MRZ) in cerebrospinal fluid
      (CSF) remains controversial in cases of acute optic neuritis (AON). This study
      evaluates the prognostic value of baseline CSF and serum markers in AON, and
      correlates them with magnetic resonance imaging (MRI) and progression to multiple
      sclerosis (MS). Paired CSF and serum samples from 36 AON patients, 26 MS patients
      and 22 controls were analyzed for albumin, IgG, oligoclonal IgG (OI), MRZ
      antibodies, and blood-CSF barrier function; baseline MRI scanning of the head was
      also performed. The most sensitive parameter for detection of intrathecal
      inflammation in AON was OI (75%). Baseline MRI scans revealed abnormalities in
      46% of the 28 patients with AON. Fifty percent of AON patients developed MS over
      the following 4 years. Ninety four percent of patients progressing to MS were
      positive for either OI, MRI or both. Of the AON patients initially positive for
      MRI and intrathecally-produced MRZ antibodies, 86% developed MS after 4 years.
      Only 17% of AON patients with negative results for OI and MRI developed MS. Six
      patients with abnormal OI but normal MRI progressed to MS. CSF and serum
      analyses, together with MRI, are the methods of choice for prognostic evaluation
      of patients with AON.

PMID- 9562323
TI  - Sympathetic skin response in patients with lateral medullary syndrome.
AB  - We have carried out a prospective study of the sympathetic skin response (SSR) in
      21 patients with lateral medullary syndrome (LMS), with the aim of identifying
      the most common pattern of SSR abnormalities and its possible correlation with
      clinical and radiological findings. The amplitude of the SSR recorded in the
      ipsilateral hand to the infarct was abnormally reduced in the patients as a
      group. However, using different stimulation and recording sites, and considering
      only the presence or absence of the response, we identified 5 different patterns
      of SSR abnormalities: 1. Normal responses; 2. Bilaterally absent responses to
      stimulation of the ipsilateral supraorbital nerve but not to other stimulation
      sites; 3. Absent responses in the side ipsilateral to the stroke, with normal
      responses in the contralateral side; 4. A combination of patterns 2 and 3; and 5.
      Absent responses to all stimuli. All patients with ipsilateral facial sensory
      loss had absent SSR to ipsilateral supraorbital nerve stimulation, while there
      was only a positive correlation between abnormal contralateral facial sensation
      and preservation of the SSR (Fisher's exact test P=0.003). No correlation was
      found between the pattern of SSR abnormalities and the infarct topography,
      assessed with the MRI. Our findings suggest that the damage to the SSR circuits
      of patients with LMS is not uniform, and follows an heterogeneous distribution
      independent from the MRI findings, and poorly related to the clinical sensory
      manifestations.

PMID- 9562324
TI  - Differentiation of idiopathic Parkinson's disease from striatonigral degeneration
      and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine
      myocardial scintigraphy.
AB  - Iodine-123 meta-iodobenzylguanidine ([123I]MIBG), an analogue of norepinephrine,
      is a tracer for functioning of sympathetic neurons. To investigate cardiac
      sympathetic function in PD, SND, and PSP, [123I]MIBG myocardial scintigraphy was
      performed in 25 patients with PD, 15 patients with SND, 14 patients with PSP, and
      20 control subjects. In planar imaging studies, the heart-to-mediastinum average
      count ratio (H/M) was calculated for both early and delayed images. The mean
      value of H/M in patients with PD was significantly lower than those with SND,
      PSP, or no disease. Regardless of disease severity or intensity of anti
      Parkinsonian pharmacotherapy, mean values for H/M were always low in patients
      with PD. The mean value of H/M in SND with orthostatic hypotension (OH) was lower
      than that in SND without OH. Although the mean value of H/M in PSP with
      amitriptyline treatment was significantly lower than that in PSP patients without
      amitriptyline treatment, there was no significant difference between the mean
      value of H/M in PSP patients without amitriptyline treatment and that in control.
      Thus, PD may have a abnormality of cardiac sympathetic function which has not
      been detected by previous cardiovascular autonomic studies. Moreover,
      particularly in early stages, [123I]MIBG myocardial scintigraphy may provide
      helpful diagnostic information in these akinetic-rigid syndromes.

PMID- 9562325
TI  - BCL-2 family protein expression in human malignant glioma: a clinical
      pathological correlative study.
AB  - Malignant gliomas are rather refractory to current therapeutic approaches
      including surgery, radiotherapy, chemotherapy and immunotherapy. Acquired
      alterations in the pathways required for apoptotic cell death are thought to be
      responsible to the failure of glioma to respond to therapy. Here we have examined
      the expression of several proteins involved in the susceptibility to apoptosis in
      20 human gliomas, including the BCL-2 family proteins BCL-2, BCL-X, BAX and MCL
      1, as well as p53 and RB. Most gliomas expressed several BCL-2 family proteins.
      There was good correlation between expression of the functional antagonists, BCL
      2/BCL-X and BAX, suggesting that changes in the BCL-2+BCL-X/BAX ratio are not
      responsible for the differential response of glioma patients to chemotherapy. The
      immunochemistry data were also analysed in regard to response to therapy and
      clinical outcome. All patients had cytoreductive surgery and received
      radiotherapy and nitrosourea-based adjuvant chemotherapy. There was no prominent
      association of outcome with the expression patterns of p53, RB, BCL-2, BCL-X or
      BAX. We find, however, that expression of the MCL-1 protein is associated with
      early tumour recurrence and shorter survival in this group of glioma patients.
      This preliminary observation will have to be confirmed in a larger independent
      sample of glioma patients.

PMID- 9562327
TI  - Distribution of cerebellar cortical lesions in multiple system atrophy: a
      topographic neuropathological study of three autopsy cases in Japan.
AB  - We investigated neuropathologically the distribution of the cerebellar cortical
      lesions in three Japanese autopsy cases of multiple system atrophy (MSA) using
      hemisphere specimens. The lesions were classified as mild, moderate or severe.
      The distribution of cerebellar cortical lesions in all three cases were uniform:
      the cerebellar cortical lesions were more conspicuous in the vermis than in the
      hemisphere. These neuropathological findings differ from the established theory
      that cerebellar lesions of MSA are more pronounced in the hemisphere than in the
      vermis. The degree of cerebellar cortical lesions in our cases increased in
      relation to the duration of the disease. Our pathological data may contribute to
      the morphological differential diagnosis in various neurodegenerative disorders
      including late cortical cerebellar atrophy. Our neuropathological findings may
      also make a contribution to the neuroradiological progress in the differential
      diagnosis of spinocerebellar disease.

PMID- 9562326
TI  - Elevated serum levels of soluble E- and L-selectin in patients with human T-cell
      lymphotropic virus type I-associated myelopathy.
AB  - We compared soluble E-selectin (sE-selectin) and L-selectin (sL- selectin) levels
      in sera and cerebrospinal fluid (CSF) of 30 patients with human T-lymphotropic
      virus type I (HTLV-I)-associated myelopathy (HAM), with those of 10 patients with
      the relapsing-remitting form of multiple sclerosis (MS), and 16 patients with
      other neurological diseases (OND). Serum levels of both sE-selectin and sL
      selectin, as measured by enzyme-linked immunosorbent assay, were significantly
      elevated in patients with HAM, compared to patients with OND. In addition, serum
      levels of sL-selectin were significantly elevated in HAM patients compared to MS
      patients. No significant difference was found in CSF levels of sL-selectin
      between HAM patients and controls. However, HAM patients who had received blood
      transfusions had significantly higher CSF levels of sL-selectin than HAM patients
      without a past history of transfusions, suggesting that HAM patients with past
      history of transfusion have a more active immunological state in the central
      nervous system. sE-selectin was not detected in CSF of HAM patients and controls.
      This finding might be based on exaggerated inflammatory conditions following
      increased attachment of lymphocytes to activated endothelial cells in HAM
      patients.

PMID- 9562328
TI  - Adult Sandhoff's disease: R505Q and I207V substitutions in the HEXB gene of the
      first Japanese case.
AB  - We describe a 31-year-old Japanese man with adult Sandhoff s disease presenting
      as spinocerebellar degeneration. There was a marked cerebellar atrophy on MRI,
      and proliferation of abundant PAS-positive foamy macrophages in the rectal
      mucosa. The activities of total beta-Hex, beta-Hex A, and beta-Hex B in
      leucocytes of the patient were 14%, 15%, and 6% of control values, respectively.
      However, oligosacchariduria or ultrastructural storage materials in liver tissue
      were nil. Direct sequencing of cDNA and genomic DNA, and restriction digestion
      revealed two different homozygous base substitutions in the HEXB gene: the G1514-
      >A substitution (R505Q) and the A619-->G substitution (1207V). The parents were
      consanguineous. His healthy mother, an enzymatic heterozygous carrier, was
      homozygous for 1207V, but heterozygous for R505Q mutation. Thus, the patient is
      probably homozygous for both base substitutions and a R505Q mutation may be
      linked to the phenotype of adult Sandhoff's disease.

PMID- 9562329
TI  - Cerebrospinal fluid cyclic guanosine 3'5' monophosphate levels in Parkinson's
      disease.
AB  - We measured CSF and plasma levels of cGMP in 22 patients with Parkinson's disease
      (PD) and in 28 age and sex-matched controls. PD patients had similar plasma cGMP
      levels than those of controls, although they showed a non-significant trend
      towards higher CSF cGMP levels (P=0.07). PD patients treated with levodopa showed
      significantly higher CSF cGMP levels than those not treated with this drug
      (P<0.01), and controls (P<0.01). However, treatment with dopamine agonists did
      not influence CSF cGMP levels. Plasma and CSF levels of cGMP did not correlate
      with age at onset, duration, and severity of PD. These results suggest that
      changes in the concentration of cGMP in CSF of patients with PD are not related
      with the disease, but rather with levodopa therapy.

PMID- 9562330
TI  - Disturbances of antagonistic neck innervation in patients with cerebellar
      deficits.
AB  - Fast 60 degree head rotations of nine patients with cerebellar deficits were
      analysed and compared with those of nine normal subjects. The surface EMG
      activity from both Splenii capitis muscles were recorded. The triphasic pattern
      of reciprocal innervated neck muscles with regard to the duration, amplitude and
      onset of the pulses were analysed together with the dynamic features of head
      rotation, i.e. position and acceleration profiles. The deviation of the onset of
      the antagonistic (B) pulse of the EMG-pattern flow was substantially increased.
      In most cases the onset of the B-pulse was delayed, less premature and sporadic
      regular onsets occurred. The number of co-contractions and multiple antagonistic
      pulses was significantly increased. Half of the movements of patients were found
      to be dysmetric, with an irregular flow of position and acceleration functions.
      From these, mainly hypermetric movements occurred. The number of irregular pulse
      patterns was higher than the number of dysmetrias. In this context
      cocontractions, multiple antagonistic pulses and cortical control can be
      discussed as strategies of the cerebellar patients to improve their dynamic
      output. Our experiments support the notion of the cerebellum playing an important
      part in the temporal integration of an antagonistically innervated movement. The
      measurement of electromyographic burst patterns can be used as a clinical tool to
      demonstrate an insufficient timing of the activities of muscles involved.

PMID- 9562331
TI  - Quantitative ocular tests for myasthenia gravis: a comparative review with
      detection theory analysis.
AB  - Many reports in the literature describe a variety of ocular signs in myasthenia
      gravis. To determine the utility of laboratory recordings of ocular signs in the
      evaluation for myasthenia, we reviewed all previous studies of quantitative
      measures of eye movements or intra-ocular pressures. We selected those studies
      with data presented for both myasthenic and non-myasthenic ocular palsies. Signal
      detection theory was used to evaluate the discriminative power of each variable.
      The characteristics of saccades and quick phases of optokinetic nystagmus at the
      start of recording were poor at distinguishing between myasthenic and non
      myasthenic palsies, except when the comparison was solely between myasthenia and
      chronic progressive external ophthalmoplegia. The effects of fatigue on saccadic
      parameters were also not discriminative, though there was insufficient data to
      evaluate this adequately. Changes induced by edrophonium in the amplitude or peak
      velocity of saccades or optokinetic quick phases were good diagnostic tests,
      retaining high sensitivities when criteria were set to yield a specificity of
      95%. Most of these parameters were less efficient as screening tests, with modest
      specificities when criteria were set to yield a sensitivity of 95%. The change in
      optokinetic quick phase amplitude recorded by infrared oculography was the best
      test, with ideal characteristics of 97% specificity and sensitivity at a
      criterion of zero change. This analysis suggests that eye movement recordings of
      saccades or optokinetic nystagmus have potential as useful and inexpensive tests
      for myasthenia, and warrant further study.

PMID- 9562332
TI  - Primary motor cortex isolation: complete paralysis with preserved primary motor
      cortex.
AB  - We present a left-sided hemiplegic patient with a cerebrovascular lesion
      involving the medial part of the right frontal and parietal lobes and the corpus
      callosum, but sparing the hand area of right primary motor cortex (M1). Several
      studies using transcranial magnetic stimulation demonstrated functional integrity
      of the efferent pathways from the right M1, intact sensory afferents to M1, an
      impairment of transcallosal connection between the bilateral motor cortices, and
      reduced ipsilateral cortico-cortical inhibition within the right M1. Based on
      these results, we conclude that the paralysis of this patient was caused by
      disconnection of the intact M1 from any structures requisite for initiation of
      movements. The present patient also suggests the importance of various afferents
      to M1 in voluntary movement. We propose a term of 'primary motor cortex
      isolation' to designate the paralysis reported here.

PMID- 9562333
TI  - IGF/IGFBP axis in cartilage and bone in osteoarthritis pathogenesis.
AB  - In the context of joint biology, insulin-like growth factor-1 (IGF-1) is the most
      likely candidate to affect the anabolism of cartilage matrix molecules.
      Mechanisms for controlling the effects of IGF-1 include alterations in the level
      of this growth factor, its receptor and/or the IGF-1 affinity or availability to
      its receptor. Disturbance of any one of the above elements may induce a
      disregulation of the mechanisms involved in the local control of joint tissue
      integrity. This review focuses on recent studies of the IGF system, and the
      potential relevance of these results to in vivo effects in osteoarthritic (OA)
      tissues. It has been shown that, although the IGF-1's expression and synthesis
      are increased in OA cartilage, chondrocytes are hyporesponsive to IGF-1
      stimulation. This phenomenon appears to be related, at least in part, to an
      increased level of IGF-binding proteins (IGFBP). The IGFBP have a high affinity
      for IGF-1, and appear to be important biomodulators for IGF action. Though to
      date seven IGFBP have been cloned and sequenced, disregulation in IGFBP-3 and -4
      appears instrumental to arthritic disorders. Proteolytic activity directed
      against IGFBP has been found in both cartilage and bone; this activity appears to
      belong to serine- and/or metallo-proteases families. It has been suggested that a
      thickening of the subchondral bone participates in OA pathophysiology, and that
      IGF-1 production by bone and/or subchondral bone cells may contribute to these
      changes. An abnormal regulation of subchondral bone formation via an increase in
      the local activation of IGF-1 in bone cells, possibly via abnormal IGFBP
      synthesis due to aberrant PA/plasmin regulation of the IGF-I/IGFBP system, is
      believed to be a plausible hypothesis.

PMID- 9562334
TI  - Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) enhance
      lipopolysaccharide binding to neutrophils via CD14.
AB  - OBJECTIVE: Lipopolysaccharide (LPS), a potent and pleiotropic stimulator of
      immune cells, binds to neutrophils via CD14, but less densely than to monocytes.
      The present study was designed to investigate whether cytokines modulate LPS
      binding to neutrophils via CD14. METHODS: Neutrophils were cultured with LPS
      after pretreatment with cytokines, interferon-gamma (IFN-gamma), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), or granulocyte-colony
      stimulating factor (G-CSF). Binding of LPS and CD14 expression on neutrophils
      were analyzed by flow cytometry, using anti-LPS and anti-CD14 monoclonal
      antibodies (mAb). RESULTS: LPS alone showed only slight binding to neutrophils,
      but pretreatment with IFN-gamma or TNF-alpha before LPS exposure markedly
      increased LPS binding and CD14 expression on the surfaces of neutrophils. The
      dramatic increase in LPS binding was not seen with IL-1alpha or G-CSF. Anti-CD14
      blocking mAb completely inhibited the binding effect. CONCLUSIONS: These results
      demonstrate that IFN-gamma and TNF-alpha enhance LPS binding to neutrophils via
      CD14, suggesting that the priming effect of cytokines on neutrophils is important
      for LPS binding.

PMID- 9562335
TI  - The role of tissue mast cells in polyacrylamide gel-induced inflammation in mice.
AB  - OBJECTIVE AND DESIGN: In the present study, we investigated the role of mast
      cells in a model of polyacrylamide gel (PAG)-induced inflammation in mice.
      SUBJECTS: Balb/c mice and two strains of mast cell deficient mice (WBB6F1/J-W/Wv,
      WCB6F1/J-S1/S1d). TREATMENT: Various quantities of polyacrylamide gel (Bio-Gel
      P4) were injected subcutaneously in the backs of mice. METHODS: Five hours after
      the injection of PAG the animals were euthanized, the injection sites lavaged and
      levels of LTB4, PGE2, TNF alpha and cells were determined. RESULTS: Subcutaneous
      injection of PAG caused a time-dependent response characterized by the
      accumulation of inflammatory cells peaking at 10 h and the formation of LTB4,
      PGE2 and TNF alpha, peaking at 5 h. PAG injection into W/Wv or SL/SLd mice (mice
      lacking mast cells) resulted in an attenuated response, i.e. LTB4 levels were
      reduced by 60% and minimal cell influx was seen. The lack of mast cells caused
      about a 30% reduction in the levels of TNF alpha found. CONCLUSIONS: These data
      suggest that mast cells play a prominent role in the PMN influx, TNF alpha
      production and eicosanoid formation in the PAG-induced inflammatory response.

PMID- 9562336
TI  - Effect of ebselen on IL-1-induced alterations in cartilage metabolism.
AB  - OBJECTIVE: To evaluate the effect of the antioxidant-like anti-inflammatory
      agent, ebselen, on cartilage proteoglycan degradation and to determine whether
      its cartilage protectant activity is related to its antioxidant activity.
      MATERIALS AND METHODS: Cartilage in organ culture was stimulated with interleukin
      1 (IL-1), and proteoglycan degradation was assessed by measuring the amount of
      sulfated glycosaminoglycan released into the media, proteoglycan synthesis
      evaluated by [35S]-sulfate incorporation, and prostaglandin E2 (PGE2) release
      determined by radioimmunoassay (RIA). Glutathione peroxidase (GSH-Px) activity
      was evaluated in a coupled test system using NADPH/GSSG reductase as an indicator
      and cyclooxygenase activity was evaluated using sheep seminal vesicle
      prostaglandin synthase. RESULTS: Ebselen caused a concentration-dependent
      inhibition of IL-1-stimulated proteoglycan degradation with an IC50 of 4.7
      microM. Cartilage PGE2 release was also reduced in the presence of ebselen (IC50
      = 6.2 microM). However, at concentrations up to 100 microM, ebselen had no effect
      on the inhibition of proteoglycan synthesis by IL-1. Induction of proteoglycan
      breakdown was also inhibited by a sulfur analog of ebselen. This analog was
      devoid of GSH-Px activity and was 50-fold less potent in cyclooxygenase
      inhibitory activity, but was equipotent to ebselen in inhibiting cartilage
      degradation. CONCLUSIONS: Ebselen, unlike other NSAIDs, blocks cartilage
      proteoglycan breakdown without inhibiting proteoglycan synthesis. This effect is
      independent of its GSH-Px activity and its ability to inhibit cyclooxygenase and
      PGE2 production. Therefore, this compound may provide a new mechanism for
      protecting cartilage matrix from degradative factors in arthritic joints.

PMID- 9562338
TI  - Effects of cinitapride on gastric ulceration and secretion in rats.
AB  - OBJECTIVE AND DESIGN: The aim of the present study was to examine the effects of
      cinitapride, a novel prokinetic benzamide-stimulating gastrointestinal motility
      agent, on gastric secretion and ulceration in rats and elucidate some possible
      vascular and anti-oxidant mechanisms of such protection. MATERIAL: Male Wistar
      rats. TREATMENT: Cinitapride (CNT, Lab. Almirall, S.A.) (0.25, 0.5, and 1 mg/kg)
      and 5-hydroxytryptamine (5-HT, Sigma Chemical Co., St. Louis, MO, USA) (10
      mg/kg), administered intraperitoneally (i.p.). METHODS: Gastric ulceration was
      induced by instillation of 1 mL/100 g animal of 50% (v/v) ethanol in distilled
      water and by pylorus-ligated rat model. Gastric microvascular changes, and the
      activity of myeloperoxidase (as a marker of neutrophil infiltration) and
      glutathione peroxidase (an important enzyme in scavenging of lipid peroxides)
      were determined. The results were compared with those of 5-HT. The data were
      evaluated using Student's t-test for paired data and the non-parametric Mann
      Whitney U-test. RESULTS: In 4 h pyloric-ligated animals, i.p. CNT did not
      significantly reduce the incidence of gastric mucosal damage, and no significant
      differences were found in the values of total volume and acidity. However, CNT
      caused a marked and dose-dependent reduction of haemorrhagic lesions induced by
      50% v/v ethanol. These protective effects were specifically related to a
      reduction of neutrophil infiltration. CNT at the dose of 1 mg/kg raised the
      decreased glutathione peroxidase activity to the control level. In contrast,
      pretreatment with 5-HT worsened the ethanol-induced erosions, but did not
      significantly induce any gastric microvascular changes. However, the
      myeloperoxidase activity rose markedly and the glutathione peroxidase levels
      decreased significantly in the mucosa injured by 50% v/v ethanol. CONCLUSIONS:
      This study demonstrates a new gastroprotective feature of CNT that could be
      partly explained not only through reduction of neutrophil toxicity but also by an
      increased synthesis of free-radical scavenging enzymes such as glutathione
      peroxidase. Furthermore, it is likely that serotonergic-dependent mechanisms are
      also involved via 5-HT2-receptor blockade and 5-HT1 receptor activation.

PMID- 9562337
TI  - Histamine release from rat mast cells induced by the metabolic activation of
      drugs of abuse into free radicals.
AB  - BACKGROUND: The metabolic activation of morphine, cocaine and methadone into free
      radicals could have pathophysiological relevance in the organic injuries of drug
      addiction. METHODS: Isolated purified rat serosal mast cells were incubated with
      morphine, cocaine and methadone (10(-7) M-10(-4) M) with oxidative enzymes
      (prostaglandin-H-synthetase, 25 mU; rat liver homogenate fraction S 10-mix, 400
      microl), and with the drugs of abuse in the presence of oxidative enzymes.
      Histamine and lactate dehydrogenase (LDH) were analysed with a fluorimetric and
      spectrophotometric assay, respectively; the generation of malonyldialdehyde (MDA)
      was measured by a spectrophotometric assay. RESULTS: The release of mast cell
      histamine and the generation of MDA are present only when mast cells were
      incubated with the drugs of abuse in the presence of oxidative enzymes. This
      release was dependent on the concentration of the drug in question and showed a
      maximum value at 10(-4) M. Moreover, in parallel experiments we demonstrated
      that, under the same experimental conditions, the release of LDH was always less
      than 20% of the total, suggesting that this effect is due to a selective
      exocytotic process. Histamine release and MDA generation were abated by the free
      radical scavengers: reduced glutathione, 10(-4) M GSH and alpha-tocopherol, 10(
      4) M and by the spin trapper 5.5-dimethyl-1-pyrroline-N-oxide, 10(-4) M DMPO. The
      light and electron microscopic features are consistent with exocytotic secretion
      in the cases of morphine and methadone and with cell lysis in the case of
      cocaine. CONCLUSION: These results suggest that morphine, cocaine and methadone
      are activated into free radicals which produce membrane lipid perturbation and
      histamine release, suggesting that a massive release of mast cell histamine could
      be an additional risk factor in heroin and cocaine overdoses.

PMID- 9562339
TI  - The effect of tyrosine kinase inhibitors on IgE-mediated histamine release from
      human lung mast cells and basophils.
AB  - OBJECTIVE AND DESIGN: To investigate the role of tyrosine kinases (TK) in IgE
      mediated signal transduction in human lung mast cells (HLMC) and basophils.
      MATERIALS: Peripheral blood basophils (n > or = 4) and human lung mast cells (n >
      or = 6). TREATMENT: Cells were preincubated with TK inhibitor for 15 min at 37
      degrees C, before the addition of anti-IgE. METHODS: Histamine release (HR) was
      assayed using a fluorimetric technique. Results were compared using nonparametric
      statistics. RESULTS: Piceatannol and ST638 significantly (p < or = 0.05)
      inhibited anti-IgE induced HR from HLMCs and basophils whilst lavendustin C had
      no effect in either cell type. Herbimycin A also significantly (p < or = 0.05)
      inhibited anti-IgE induced HR from both cell types, an effect which was dose
      dependent but did require a 16 h preincubation with drug. CONCLUSIONS: In
      summary, HLMCs and basophils exhibit distinct inhibitory profiles in the presence
      of various inhibitors of TK.

PMID- 9562340
TI  - Insulin-induced vasodilatation: physiology or pharmacology?

PMID- 9562342
TI  - Effects of alpha-lipoic acid on neurovascular function in diabetic rats:
      interaction with essential fatty acids.
AB  - Elevated oxidative stress and impaired n-6 essential fatty acid metabolism
      contribute to defective nerve conduction velocity (NCV) and perfusion in diabetic
      rats, which may be corrected by free radical scavenger and gamma-linolenic acid
      (GLA) treatments. Alpha-lipoic acid (LPA) has antioxidant actions and both LPA
      racemate (racLPA) and GLA treatments produced benefits in clinical neuropathy
      trials. The aims were to study LPA action on neurovascular function in diabetic
      rats and to investigate potential interactions for co-treatment with GLA and
      other essential fatty acids. After 6 weeks of diabetes, 2 weeks of racLPA
      treatment corrected 20% sciatic motor and 14% saphenous sensory NCV deficits. The
      ED50 for motor NCV restoration was approximately 38 mg kg(-1) day(-1). racLPA
      also corrected a 49% diabetic deficit in sciatic endoneurial blood flow. R and S
      LPA enantiomers were equipotent in correcting NCV and blood flow deficits.
      Treatment of diabetic rats with low doses (20 mg kg(-1) day(-1)) of racLPA and
      GLA, while having modest effects on their own, showed evidence of marked
      synergistic action in joint treatment, completely correcting motor NCV and blood
      flow deficits. This was also noted for the novel compound, SOC0150, which
      contains equimolar proportions of LPA and GLA (ED50 9.3 mg kg(-1) day(-1),
      containing 3.5 mg LPA). NCV effects also showed marked synergism when racLPA:GLA
      ratios were varied over a 1:3-3:1 range. In contrast, a compound containing LPA
      and the n-3 component, docosahexaenoic acid, showed similar activity to LPA
      alone. Thus, LPA-GLA interactions yield drug combinations and compounds with an
      order of magnitude increase in efficacy against experimental diabetic neuropathy
      and are worthy of consideration for clinical trials.

PMID- 9562341
TI  - Improvement of insulin sensitivity and cardiovascular outcomes in the JCR:LA-cp
      rat by D-fenfluramine.
AB  - Obese male rats of the JCR:LA-cp strain are insulin resistant, normoglycaemic,
      hypertriglyceridaemic, and atherosclerosis-prone. Such rats were treated from 6
      to 39 weeks of age with 5 mg x kg(-1) x day(-1) of D-fenfluramine. The treatment
      normalised food intake, after 20 weeks of age, to that of lean control animals.
      At 39 weeks, treated rats weighed about 650 g compared to 800 g for untreated
      cp/cp rats and 400 g for +/+ controls. Fasting plasma glucose and triglyceride
      levels were not significantly affected; however, fasting insulin concentrations
      were lower and the size and volume density of the hyperplastic islets of
      Langerhans were markedly reduced. The severity of raised atherosclerotic lesions
      on the aortic arch was decreased by 39% (p < 0.01). Concomitantly, the occurrence
      of mature, scarred ischaemic myocardial lesions was virtually abolished (p <
      0.01). Severe food restriction of the obese rats to normalise body weights to
      those of lean controls reduced plasma insulin and triglyceride concentrations at
      26 weeks of age, but without a significant reduction in the frequency of
      myocardial lesions. Rats (with established insulin resistance) were treated from
      6 to 12 weeks of age with 2.5 mg x kg(-1) x day(-1) of D-fenfluramine. Insulin
      mediated glucose turnover during a euglycaemic insulin clamp was strongly
      increased (p < 0.05). Rats treated from 3 weeks of age (before development of the
      insulin resistance) showed a significant delay in the development of
      hyperinsulinaemia and a reduced postprandial increase in plasma insulin. In
      contrast, restriction of food to that consumed by rats treated with D
      fenfluramine did not decrease post-absorptive hyperinsulinaemia. D-fenfluramine
      treatment markedly improved the maximum relaxant response of aortic rings to
      acetylcholine, indicating improvement of the defective endothelium-derived
      relaxation factor system. A matched-food restriction regimen had no effect on
      vascular relaxation. D-fenfluramine treatment thus improved insulin sensitivity
      and had anti-atherosclerotic and cardioprotective effects in the presence of
      continuing obesity and hyperlipidaemia. The results are consistent with the
      protection of the function and integrity of the vessel wall associated with a
      decreased hyperinsulinaemia. The results emphasise the importance of focussing
      treatment of the metabolic syndrome (obesity/insulin resistance/hyperlipidaemia)
      on improving insulin sensitivity and glycaemic control rather than on the simple
      normalisation of body weight.

PMID- 9562343
TI  - Role of JTT-501, a new insulin sensitiser, in restoring impaired GLUT4
      translocation in adipocytes of rats fed a high fat diet.
AB  - JTT-501 is an insulin-sensitising compound with an isoxazolidinedione rather than
      a thiazolidionedione structure. Sprague-Dawley rats fed a high fat diet for 2
      weeks were used as an animal model of insulin resistance, and JTT-501 was
      administered for the final week of the diet. An euglycaemic glucose clamp study
      showed that the glucose infusion rate (GIR) required to maintain euglycaemia was
      57% lower in rats fed a high fat diet than in control rats, and that JTT-501
      treatment restored the reduction in GIR produced by the high fat diet. To explain
      the mechanisms underlying the effects of a high fat diet and JTT-501 treatment,
      epididymal fat pads were excised and used in the analysis of insulin action. The
      high fat diet caused: (1) a 58% decrease in insulin receptor substrate-1 (IRS-1)
      content with a 58% decrease in IRS-1 tyrosine phosphorylation; (2) reductions of
      56% and 73% respectively in insulin-induced maximal PI 3-kinase activation in
      anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates; (3) a 46%
      reduction in the glucose transporter protein, GLUT4 content and, consequently,
      (4) severely impaired insulin-induced GLUT4 translocation to the plasma membrane
      and glucose uptake in adipocytes. JTT-501 treatment restored appreciably the
      protein content and tyrosine phosphorylation level of IRS-1. Insulin-stimulated
      PI 3-kinase activation was also restored in anti-phosphotyrosine and anti-IRS-1
      antibody immunoprecipitates. As reflected by these improvements in insulin
      signalling, JTT-501 treatment improved considerably insulin-induced GLUT4
      translocation to the plasma membrane as well as insulin-induced glucose uptake.
      However, JTT-501 had no effect on the decrease in GLUT4 content produced by the
      high fat diet. These observations suggest that JTT-501 enhances insulin
      signalling and may be effective in reducing insulin resistance.

PMID- 9562344
TI  - Pronounced skin capillary ischemia in the feet of diabetic patients with bad
      metabolic control.
AB  - Skin capillary circulation is impaired during postocclusive reactive hyperaemia
      (PRH) in toes of diabetic patients independent of diabetes duration and
      macrocirculation. The aim of this study was to examine its relation to metabolic
      control. The skin microcirculation was investigated in 20 patients with insulin
      dependent diabetes mellitus: 10 patients with bad [HbA1c > 7.5 (8.7 +/- 0.8) %],
      and 10 patients with good metabolic control [HbA1c < 7.5 (6.3 +/- 1.0) %]. The
      diabetes duration was similar in both groups (16 +/- 9 and 16 +/- 6 years,
      respectively). None had macroangiopathy. Thirteen healthy subjects served as
      controls. The capillary blood cell velocity (CBV) in the nailfold of the great
      toe was investigated by videophotometric capillaroscopy, and the total skin
      microcirculation by laser Doppler fluxmetry (LDF). CBV and LDF were studied
      during rest and after 1-min arterial occlusion. The vibration perception
      thresholds (VPT) of the feet were higher (p < 0.05) in the patients with bad (34
      +/- 12 V), as compared to patients with good metabolic control (18 +/- 10 V) and
      to healthy subjects (13 +/- 3 V). Peak CBV during PRH was reduced in both patient
      groups (p < 0.01), and lowest in the patients with bad metabolic control (p <
      0.05). Time to peak CBV was prolonged (p < 0.01) in the patients with bad, while
      normal in the patients with good metabolic control. LDF was similar in all
      groups. An inverse correlation was found between HbA1c and peak CBV during PRH (r
      = 0.60; p = 0.008), while positive correlations were found to time to peak CBV (r
      = 0.62; p = 0.004) and VPT (r = 0.60; p = 0.01). No associations were seen
      between VPT and the microcirculatory variables. The results indicate that the
      metabolic control is of importance for the nutritive capillary circulation and
      the peripheral nerve function in the diabetic foot.

PMID- 9562345
TI  - The effect of intensive diabetes therapy on measures of autonomic nervous system
      function in the Diabetes Control and Complications Trial (DCCT).
AB  - In the Diabetes Control and Complications Trial (DCCT), 1441 insulin-dependent
      diabetic patients in the primary prevention and secondary intervention cohorts
      were randomly assigned to either conventional or intensive therapy and followed
      for up to 9 years. Baseline and biennial measurements of autonomic function (R-R
      variation, Valsalva ratio, and postural testing) as well as quarterly assessment
      of autonomic symptoms were performed throughout the trial. There were no
      differences at baseline between patients randomized to intensive vs conventional
      therapy. In general, autonomic abnormalities increased during the trial; however,
      R-R variation was less abnormal in the intensively treated secondary intervention
      (7% with abnormal results at 4-6 years) compared with the conventionally treated
      group (14% with abnormal results, p = 0.004) and in the combined cohorts (5% of
      intensive treatment subjects with abnormal results vs 9% of conventional
      treatment subjects, p = 0.0017). There were few abnormal Valsalva ratios or
      postural tests at baseline or during the trial. No significant difference in
      Valsalva ratio or postural tests occurred between the intensive and conventional
      treatment groups. Both the R-R variation and the Valsalva ratio had significantly
      greater slopes of decline over time in the patients randomized to conventional
      therapy (1.48 points per year and 0.015 per year, respectively) compared to those
      randomized to intensive therapy (0.912 points per year and 0.0025 per year). Of
      the symptoms related to autonomic function, only incomplete bladder emptying was
      significantly more common in the conventional group. In summary, the DCCT
      documented that intensive therapy can slow the progression and the development of
      abnormal autonomic tests.

PMID- 9562346
TI  - IA-2 antibodies--a sensitive marker of IDDM with clinical onset in childhood and
      adolescence. Childhood Diabetes in Finland Study Group.
AB  - To study the relationship of IA-2 antibodies (IA-2A) to other autoantibodies and
      genetic risk markers in insulin-dependent diabetes mellitus (IDDM), 758 children
      and adolescents younger than 15 years of age (mean age 8.4 years) with newly
      diagnosed diabetes were analysed for IA-2A, GAD antibodies (GADA) and insulin
      autoantibodies (IAA) with radiobinding assays, for islet cell antibodies (ICA)
      with immunofluorescence and for HLA DR alleles by serology. IA-2A were detected
      in 85.9% of cases with no association with gender or age. An overwhelming
      majority of the patients (71.3%) tested positive for three or more antibodies,
      and 90.7% for at least two. Fifty-four subjects (7.1%) had one antibody
      detectable, whereas only 2.1% of the patients tested negative for all four. A
      higher proportion of patients was positive for IA-2A and/or GADA than for ICA
      alone (95.5 vs 84.2%, p < 0.001). The prevalence and level of IA-2A were
      increased in cases carrying HLA DR4/non-DR3 compared with other DR combinations.
      The results indicate that almost all patients with newly diagnosed childhood IDDM
      can be identified by screening with these four autoantibodies. The combination of
      IA-2A and/or GADA had a higher sensitivity for IDDM than ICA alone. The close
      association between IA-2A and HLA DR4, the strongest single allele predisposing
      to IDDM, suggests that IA-2A may be a more specific marker of beta-cell
      destruction than GADA, which have been shown to associate with the DR3 allele and
      thyroid autoimmunity.

PMID- 9562347
TI  - Tumour necrosis factor-alpha gene promoter polymorphism and decreased insulin
      resistance.
AB  - Insulin resistance is a feature of non-diabetic relatives of non-insulin
      dependent diabetic (NIDDM) families. Tumour necrosis factor-alpha (TNF alpha)
      expression is linked with insulin resistance, and is under strong genetic
      control. We examined the relationship between insulin resistance and two
      polymorphisms of the TNF alpha promoter region (positions -238 and -308). Non
      diabetic relatives (n = 123) of NIDDM families and control subjects (n = 126)
      with no family history of diabetes were studied. Insulin resistance was
      determined by homeostasis model assessment (HOMA) and short insulin tolerance
      test (ITT), and genotyping was by restriction digest. The -238 polymorphism (TNFA
      A allele) was carried by 14 relatives and 11 control subjects, and all were
      heterozygotes. To examine the relationship between the -238 polymorphism and
      insulin resistance independent of potentially confounding factors, the relatives
      with the TNFA-A allele were individually pair-matched for age, sex, waist-hip
      ratio, body mass index, and glucose tolerance with relatives homozygous for the
      wild-type allele. Relatives with the TNFA-A allele had decreased insulin
      resistance (HOMA index: 2.0, 3.6 +/- 2.1 [means +/- SD of differences], p =
      0.03), and this was true for comparable pair-matched control subjects (HOMA
      index: 1.1, 1.9 +/- 0.8, p = 0.01). Combining relative (n = 7) and control (n =
      4) pairs that had undergone an ITT, subjects with the TNFA-A allele had an
      increased K(ITT) (3.8, 3.0 +/- 1.0%/min, p = 0.04) similarly indicating decreased
      insulin resistance. There was no significant relationship between the -308
      polymorphism and insulin resistance. We conclude that the TNFA-A allele is
      associated with decreased insulin resistance as assessed by two independent
      methods, and may protect against the future development of NIDDM in susceptible
      individuals.

PMID- 9562348
TI  - Uptake mechanisms for ascorbate and dehydroascorbate in lymphoblasts from
      diabetic nephropathy and hypertensive patients.
AB  - In diabetic nephropathy and hypertension, a major cause of mortality is from
      cardiovascular disease. Since low levels of antioxidants such as vitamin C have
      been associated with such complications, we have examined the uptake mechanisms
      for ascorbic acid (AA) and dehydroascorbic acid (DHA) in lymphoblasts from normal
      control subjects (CON), normoalbuminuric insulin-dependent diabetic (IDDM)
      patients (DCON), patients with IDDM and nephropathy (DN) and hypertensive
      patients (HT) using mass assays of uptake and measuring AA using high-performance
      liquid chromatography. Precautions were taken to prevent oxidation of AA and to
      take into account the instability of DHA in buffers. DHA uptake was the major
      mechanism in all four groups of subjects, and the Vmax (maximal uptake rate) was
      significantly lower in the DN cells (24.7 +/- 1.0 nmol [95% confidence intervals
      CI 22.5, 26.3] 10(6) cells(-1) h(-1)) compared to CON and DCON cells (33.9 +/-
      2.1 [95% CI 29.4, 38.4] and 37.0 +/- 2.2 [95% CI 32.2, 41.8] nmol 10(6) cells(-1)
      h(-1), respectively, p < 0.001 for both). DHA Vmax was also lower in the HT group
      (23.2 +/- 1.1 [95% CI 20.7, 25.7] nmol 10(6) cells(-1) h(-1)) compared to the CON
      group (p < 0.001). There were no significant differences in the Km or passive
      membrane permeability for DHA or the AA uptake. DHA uptake showed a negative
      correlation to systolic blood pressure (r(s) = -0.49, p < 0.001). These findings
      suggest that impaired DHA uptake may be one component of the phenotype expressed
      by DN cells that may persist in culture. Impaired DHA uptake in vivo, especially
      in the presence of hyperglycaemia, leads to impaired regeneration of AA and
      depletion of anti-oxidant defences, exposing such individuals to increased risk
      of cardiovascular disease.

PMID- 9562349
TI  - Effect of glycaemic control on myocardial sympathetic innervation assessed by
      [123I]metaiodobenzylguanidine scintigraphy: a 4-year prospective study in IDDM
      patients.
AB  - Diabetic cardiovascular autonomic neuropathy (CAN) has been directly
      characterized by reduced or absent myocardial [123I]metaiodobenzylguanidine
      (MIBG) uptake, but there is no information available on the relationship between
      the myocardial adrenergic innervation defects and long-term glycaemic control. In
      a prospective study over a mean of 4 years we examined myocardial sympathetic
      innervation in 12 Type 1 (insulin-dependent) diabetic patients using MIBG
      scintigraphy (absolute and relative global MIBG uptake at 2 h p.i.) in
      conjunction with cardiovascular autonomic function tests, QTc interval, and QT
      dispersion. Six healthy non-diabetic subjects served as controls for the MIBG
      scintigraphy at baseline. HbA1c was measured twice a year. One patient, in whom
      MIBG accumulation was reduced maximally, died during follow up. Among the
      remaining patients 5 had good or borderline glycaemic control (mean HbA1c < 7.6%;
      Group 1), whereas 6 patients were poorly controlled (mean HbA1c > or = 7.6%;
      Group 2). Absolute global MIBG uptake increased from baseline to follow-up by 260
      (-190-540) [median (range)] cpm/g in Group 1 and decreased by -150 (-450-224)
      cpm/g in Group 2 (p < 0.05 vs Group 1). Relative global MIBG uptake decreased by 
      1.7 (-3.4-9.4) % in Group 1 and by -4.7 (-17.4-1.3) % in Group 2 (p < 0.05 vs
      Group 1). No differences between the groups were noted for the changes in the
      automatic function tests, QTc interval, and QT dispersion. In conclusion, long
      term poor glycaemic control constitutes an essential determinant in the
      progression of left ventricular adrenergic dysinnervation which may be prevented
      by near-normoglycaemia. Evaluation of susceptibility to metabolic intervention
      may be superior when CAN is characterized directly by MIBG scintigraphy rather
      than by indirect autonomic function testing.

PMID- 9562351
TI  - Soluble vascular cell adhesion molecule-1 and E-selectin levels in relation to
      vascular risk factors and to E-selectin genotype in the first degree relatives of
      NIDDM patients and in NIDDM patients.
AB  - To investigate the metabolic and genetic associations of levels of soluble
      adhesion molecules, plasma levels of soluble E-selectin and vascular cell
      adhesion molecule-1 were measured in 60 non-insulin-dependent diabetes mellitus
      (NIDDM) patients, 60 first-degree relatives of NIDDM patients and 60 control
      subjects, none of whom displayed clinical features of vascular disease. In
      addition, E-selectin A561C genotype, coding for a serine to arginine change, was
      determined. E-selectin levels were elevated in the patient group; 57 [52-63]
      (mean [95% confidence intervals]) ng/ml, compared with both relatives; 44 [39-50]
      ng/ml p = 0.001 and controls 39.5 [36-43] ng/ml p = 0.0001. E-selectin levels
      correlated with triglycerides, tissue-plasminogen activator and plasminogen
      activator inhibitor-1 activity in all groups. Levels of E-selectin were related
      to E-selectin genotype, being higher in subjects possessing the arginine allele
      (51.4 vs 44.5 ng/ml p < 0.05). E-selectin levels were higher in males than
      females in controls (female 35 [32-39] vs male 45 [40-51] ng/ml p = 0.004), and
      NIDDM relatives (female 38 [33-44] vs male 52 [45-61] ng/ml p = 0.004) but not in
      NIDDM patients where levels were similar (female 58 [49-69] vs male 56 [50-62]
      ng/ml, ns). There was no difference in soluble vascular cell adhesion molecule-1
      levels between the three groups (control 640 [598-686] ng/ml, NIDDM relatives 634
      [593-678] ng/ml and NIDDM patients 664 [608-725] ng/ml). In controls and patients
      vascular cell adhesion molecule-1 levels correlated with von Willebrand factor
      (vWF). The results indicate that levels of E-selectin relate to vascular risk
      factors in control subjects, NIDDM relatives and NIDDM patients.

PMID- 9562350
TI  - Implantation of standardized beta-cell grafts in a liver segment of IDDM
      patients: graft and recipients characteristics in two cases of insulin
      independence under maintenance immunosuppression for prior kidney graft.
AB  - Islet allografts in insulin-dependent diabetic (IDDM) patients exhibit variable
      survival lengths and low rates of insulin-independence despite treatment with
      anti-T-cell antibodies and maintenance immunosuppression. Use of poorly
      characterized freshly isolated preparations makes it difficult to determine
      whether failures are caused by variations in donor tissue. This study assesses
      survival of standardized beta-cell allografts in C-peptide negative IDDM patients
      on maintenance immunosuppression following kidney transplantation and without
      receiving anti-T-cell antibodies or additional immunosuppression. Human islets
      were isolated from pancreatic segments after maximal 20 h cold-preservation.
      During culture, preparations were selected according to quality control tests and
      combined with grafts with standardized cell composition (> or = 50% beta cells),
      viability (> or = 90%), total beta-cell number (1 to 2 x 10(6)/kg body weight)
      and insulin-producing capacity (2 to 4 nmol x graft(-1) x h(-1)). Grafts were
      injected in a liver segment through the repermeabilized umbilical vein. After 2
      weeks C-peptide positivity, four out of seven recipients became C-peptide
      negative; two of them were initially GAD65-antibody positive and exhibited a rise
      in titre during graft destruction. The other three patients remained C-peptide
      positive for more than 1 year, two of them becoming insulin-independent with near
      normal fasting glycaemia and HbA1c; they remained GAD65- and islet cell antibody
      negative. The three patients with surviving grafts presented a history of anti
      thymocyte globulin therapy at kidney transplantation. Long-term surviving grafts
      increased C-peptide release following intravenous glucagon or oral glucose but
      not following intravenous glucose. Thus, cultured human beta-cells can survive
      for more than 1 year in IDDM patients on maintenance anti-rejection therapy for a
      prior kidney graft and without the need for an increased immunosuppression at the
      time of implantation. The use of functionally standardized beta-cell grafts helps
      to identify recipient and graft factors which influence their survival and
      metabolic effects. Insulin-independence can be achieved by injection of 1.5
      million beta-cells per kg body weight in a liver segment. These beta-cell
      implants respond well to adenylcyclase activators but poorly to glucose.

PMID- 9562352
TI  - Chronic diabetic complications in patients with MODY3 diabetes.
AB  - MODY3 diabetes, which is caused by a mutation in the hepatocyte nuclear factor
      1alpha gene (HNF-1alpha) on chromosome 12, represents a relatively common
      monogenic form of diabetes in Finland. Age at onset of the disease can vary from
      10 to 60 years, but little is known about the natural course of the disease,
      particularly the development of diabetes-related chronic complications. The
      availability of genetic markers now allows description of the clinical course of
      the disease. In order to examine the prevalence of chronic diabetic complications
      in MODY3, we examined 57 carriers with HNF-1alpha mutations for the presence of
      micro- and macrovascular complications. Thirty-four percent of the MODY patients
      had mild and 13% had severe non-proliferative or proliferative retinopathy; this
      figure did not differ from the figures in insulin-dependent diabetes mellitus
      (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients matched for
      duration and glycaemic control but not for age. Neither did the prevalence of
      microalbuminuria differ between MODY3 and IDDM or NIDDM patients (19 vs 24 and
      23%). Neuropathy was observed with the same frequency as previously reported in
      IDDM. Hypertension was less frequent in MODY3 and IDDM than in NIDDM (24.5 and 19
      vs 53.7%; p < 0.001). Coronary heart disease was more common in MODY3 than in
      IDDM (16 vs 4.5%; p < 0.02) but less common than in the older NIDDM patients
      (33.3%; p < 0.02). In a multiple logistic regression analysis, poor glycaemic
      control was an independent risk factor for retinopathy (p = 0.03),
      microalbuminuria (p < 0.04) and neuropathy (p = 0.03). In conclusion,
      microangiopathic complications are observed with the same frequency in patients
      with MODY3 diabetes as in IDDM and NIDDM and are strongly related to poor
      glycaemic control.

PMID- 9562353
TI  - Effect of euglycaemic hyperinsulinaemia on gastric emptying and gastrointestinal
      hormone responses in normal subjects.
AB  - Several studies have shown that hyperglycaemia slows gastric emptying in normal
      subjects and patients with diabetes mellitus but whether hyperinsulinaemia per se
      has an effect remains debatable. In the present study we have assessed the effect
      of hyperinsulinaemia on gastric emptying of a solid and liquid meal in normal
      subjects. Ten men were studied three times in random order. After an overnight
      fast, subjects were infused with 0.9% NaCl on two occasions and on the third with
      insulin, at 40 mU x m(-2) x min(-1) with 20% glucose simultaneously to maintain
      euglycaemia. Steady-state glucose infusion rate was ensured before the subjects
      ate a standard meal of a pancake labelled with 99mTc and milkshake labelled with
      (111)In-DTPA. Gamma-scintigraphic images were then obtained every 20 min for the
      next 3 h. There were no significant differences between the mean half-emptying
      times (T50) of the solid and liquid during the two saline infusions (129.6 +/-
      28.5 vs 128.4 +/- 23.8 min for the solid and 25.4 +/- 7.0 vs 34.7 +/- 18.0 min
      for the liquid, mean +/- SD). Hyperinsulinaemia delayed both solid (mean T50
      149.6 +/- 30.7, p = 0.031) and liquid emptying (mean T50 39.8 +/- 13.9, p =
      0.042). There were no significant differences in the cholecystokinin and glucagon
      like peptide 1 responses to the meal during either saline or insulin infusions.
      There was a tendency towards a greater insulin response to the meal during the
      hyperinsulinaemic study. Thus, hyperinsulinaemia delayed emptying of both the
      solid and liquid components of the meal.

PMID- 9562355
TI  - Thrifty yes, genetic no.

PMID- 9562354
TI  - Hypothesis: muscle insulin resistance is the ("not-so") thrifty genotype.

PMID- 9562356
TI  - Increased interleukin-12 plasma concentrations in both, insulin-dependent and non
      insulin-dependent diabetes mellitus.

PMID- 9562357
TI  - Effect of cold exposure (-15 degrees C) and salbutamol treatment on physical
      performance in elite nonasthmatic cross-country skiers.
AB  - The effects of whole-body exposure to ambient temperatures of -15 degrees C and
      23 degrees C on selected performance-related physiological variables were
      investigated in elite nonasthmatic cross-country skiers. At an ambient
      temperature of -15 degrees C we also studied the effects of the selective beta2
      adrenergic agonist Salbutamol (0.4 mg x 3) which was administered 10 min before
      the exercise test. Eight male cross-country skiers with known maximal oxygen
      uptakes (VO2max) of more than 70 ml x kg(-1) x min(-1) participated in the study.
      Oxygen uptake (VO2), heart rate (fc), blood lactate concentration ([La-]b) and
      time to exhaustion were measured during controlled submaximal and maximal running
      on a treadmill in a climatic chamber. Lung function measured as forced expiratory
      volume in 1 s (FEV1) was recorded immediately before the warm-up period and at
      the conclusion of the exercise protocol. Submaximal VO2 and [La-]b at the two
      highest submaximal exercise intensities were significantly higher at -15 degrees
      C than at 23 degrees C. Time to exhaustion was significantly shorter in the cold
      environment. However, no differences in VO2max or fc were observed. Our results
      would suggest that exercise stress is higher at submaximal exercise intensities
      in a cold environment and support the contention that aerobic capacity is not
      altered by cold exposure. Furthermore, we found that after Salbutamol inhalation
      FEV1 was significantly higher than after placebo administration. However, the
      inhaled beta2-agonist Salbutamol did not influence submaximal and maximal VO2,
      fc, [La-]b or time to exhaustion in the elite, nonasthmatic cross-country skiers
      we studied. Thus, these results did not demonstrate any ergogenic effect of the
      beta2-agonist used.

PMID- 9562358
TI  - Influence of light physical activity on cardiac responses during recovery from
      exercise in humans.
AB  - To examine the influence of light exercise on cardiac responses during recovery
      from exercise, we measured heart rate (HR), stroke volume (SV), and cardiac
      output (Qc) in five healthy untrained male subjects in an upright position
      before, during, and after 10-min steady-state cycle exercise at an exercise
      intensity of 170 W, corresponding to a mean of 68 (SD 4)% of maximal oxygen
      uptake. The recovery phase was evaluated separately for three different
      conditions: 10 min of complete rest (passive recovery), 7 min of pedalling at 20
      W exercise intensity followed by 3 min of rest (partially active recovery), and 7
      min of pedalling at 40-W exercise intensity followed by 3 min of rest (partially
      active recovery), on an upright cycle ergometer. The time courses of decreases in
      HR in the two active recovery phases at different exercise intensities were
      almost identical to those in the passive recovery phase. However, the subsequent
      HR reductions during the rest after active recovery at 20 W and at 40 W were mean
      7.5 (SD 4.4) and mean 10.0 (SD 3.1) beats x min(-1), respectively, both of which
      were significantly larger (P < 0.05 and P< 0.005) than the corresponding
      reduction [1.4 (SD 2.5) beats min(-1)] for passive recovery. The SV values at the
      two exercise intensities during the active recovery periods were maintained at
      levels similar to that during 170-W steady-state exercise. In contrast, the SV
      during passive recovery decreased gradually to a level significantly below the
      initial baseline level at rest before exercise (P < 0.05). The resultant time
      courses of CO values during active recovery were significantly higher (each P <
      0.05) than that during passive recovery. It was concluded from these findings
      that light post-exercise physical activity plays an important role in
      facilitating the venous return from the muscles and in restoring the elevated HR
      to the pre-exercise resting level.

PMID- 9562360
TI  - Assessment of middle-distance running performance in sub-elite young runners
      using energy cost of running.
AB  - The purpose of this study was to assess the validity of v(amax) as an indicator
      of middle-distance running performance in sub-elite young runners, v(amax) being
      defined as the quotient maximal oxygen uptake (VO2max) divided by the net energy
      cost of running (Cr) on a treadmill at a submaximal running velocity (280 m x
      min[-1]). The VO2max, ventilatory threshold, v(amax), and Cr were assessed in 39
      young male sub-elite runners having only small variations in performance level.
      The relationship between each variable and running performance (at 1500 m, 3000
      m, and 5000 m) was evaluated. A trend toward a negative correlation existed
      between Cr and performance although this was not significant. The VO2max and
      v(amax) were significantly related to performance. The v(amax) accounted for
      around 50% of the variability in performance whereas other physiological
      variables selected in this study were responsible, at best, for approximately
      39%. The results presented in this study suggested that v(amax) was a useful
      indicator of middle-distance running performance in sub-elite young runners with
      similar performance levels as well as in top elite athletes.

PMID- 9562359
TI  - Acute hormone responses to heavy resistance lower and upper extremity exercise in
      young versus old men.
AB  - Acute hormone responses of growth hormone (GH), total and free testosterone (TT
      and FT) and cortisol (C) to heavy resistance isometric exercise were examined in
      ten young men [YM 26.5 (SD 4.8) years] and ten old men [OM 70.0 (SD 3.7) years].
      Loading conditions of the same relative intensity were created for the lower and
      upper extremity actions separately as well as for both of them together lower
      extremity exercise (LE; knee extension), upper extremity exercise (UE; bench
      press extension), and lower and upper extremity exercise (LUE) performed
      simultaneously in a seated position. Single voluntary maximal isometric actions
      lasting for 5 s were performed repeatedly for ten repetitions (with a recovery of
      5 s) for a total of four sets. The recovery time between the sets was 1 min. Each
      exercise led to large acute decreases in maximal isometric force in both YM (P <
      0.001) and OM (P < 0.001) ranging from 41% to 26% with no significant differences
      between the groups. Serum GH concentrations increased in both YM (P < 0.05-0.01)
      and OM (P < 0.05) but the postexercise value in YM during LE was greater (P <
      0.05) than for OM. The TT increased (P < 0.01-0.001) in YM in all three
      exercises, while in OM the increase occurred only during LE (P < 0.01). The
      exercises led to increases in FT in YM (P < 0.05 for LE and LUE), while in OM the
      increase occurred only during LUE (P < 0.05). The pre and postexercise FT were
      greater in YM (P < 0.001) than in OM. No significant changes occurred in C either
      in YM or in OM. The blood lactate concentrations increased during the exercises
      in both YM (P < 0.001) and OM (P < 0.05-0.001) but the postexercise values during
      LE and LUE in YM were greater (P < 0.05) than in OM. The present data would
      indicate that the responses of GH, TT and FT to heavy resistance isometric
      exercise are lowered with increasing age. The reduced acute hormone response
      together with the lowered basal values in FT in the older men compared to the
      young men may indicate decreased anabolic effects on muscles and may explain in
      part the loss of muscle mass and strength associated with aging.

PMID- 9562361
TI  - Heart rate variability in exercising humans: effect of water immersion.
AB  - Power spectrum analysis of heart-rate variability was made in seven men [mean age
      22 (SEM 1) years] in head-out water immersion (W) and in air (A, control) at rest
      and during steady-state cycling to maximal intensity (maximum oxygen uptake,
      VO2max). At rest W resulted in a trebled increase in the total power (P < 0.05),
      coupled with minimal changes in the power (as a percentage of the total) of the
      high frequency peak (HF, centred at 0.26 Hz; 18% vs 28%) and of the low frequency
      peak (LF, 0.1 Hz; 24% vs 32%). A third peak at about 0.03 Hz (very low frequency,
      VLF) represented the remaining power both in W and A. These changes as a whole
      indicated that immersion caused a vagal dominance in cardiac autonomic
      interaction, due to the central pooling of blood and/or the pressure of water on
      the trunk. Exercise caused a decrease in the total power in W and A. The LF% did
      not change up to about 50% V02max, thereafter decreasing towards nil in both
      conditions. The HF% decreased in similar ways in W and A to about half at 55%-60%
      VO2max and then increased to reach 1.5 times the resting values at VO2max. The
      central frequency of HF increased linearly with oxygen uptake, showing a tendency
      to be higher in W than in A at medium to high intensities. The VLF% remained
      unchanged. The lack of differences in the LF peak between W and A during exercise
      would suggest that blood distribution had no effect on the readjustments in
      control mechanisms of arterial pressure. On the other hand, the findings of
      similar HF powers and the very similar values for ventilation in W and A
      confirmed the direct effect of the respiratory activity in heart rate modulation
      during exercise.

PMID- 9562362
TI  - Failure to obtain a unique threshold on the blood lactate concentration curve
      during exercise.
AB  - The purpose of this study was to compare various methods and criteria used to
      identify the anaerobic threshold (AT), and to correlate the AT obtained with each
      other and with running performance. Furthermore, a number of additional points
      throughout the entire range of lactate concentrations [La-] were obtained and
      correlated with performance. A group of 19 runners [mean age 33.7 (SD 9.6) years,
      height 173 (SD 6.3) cm, body mass 68.3 (SD 5.4) kg, maximal O2 Uptake (VO2max)
      55.2 (SD 5.9) ml x kg(-1) x min(-1)] performed a maximal multistage treadmill
      test (1 km x h[-1] every 3.5 min) with blood sampling at the end of each stage
      while running. All AT points selected (visual [La-], 4 mmol x l(-1) [La-], 1 mmol
      x l(-1) above baseline, log-log breakpoint, and 45 degrees tangent to the
      exponential regression) were highly correlated one with another and with
      performance (r > 0.90) even when there were many differences among the AT (P <
      0.05). The additional points (ranging from 3 to 8 mmol x l(-1) [La-], 1 to 6 mmol
      x l(-1) [La-] above the baseline, and 30 to 70 degrees tangent to the exponential
      curve of [La-]) were also highly correlated with performance (r > 0.90). These
      results failed to demonstrate a distinct AT because many points of the curve
      provided similar information. Intercorrelations and correlations between AT and
      performance were, however, reduced when AT were expressed as the percentage of
      maximal treadmill speed obtained at AT or percentage of VO2max. This would
      indicate that different attributes of aerobic performance (i.e. maximal aerobic
      power, running economy and endurance) are measured when manipulating units. Thus,
      coaches should be aware of these results when they prescribe an intensity for
      training and concentrate more on the physiological consequences of a chosen [La-]
      rather than on a "threshold".

PMID- 9562363
TI  - Ventilation response to CO2 and exercise-induced hypoxaemia in master athletes.
AB  - Exercise-induced hypoxaemia (EIH) in master athletes may be related to a
      diminished exercise hyperpnoea. The aim of this study was to determine whether
      EIH is associated with a change in the sensitivity of the ventilation response to
      activation of the central chemoreceptors. The ventilation response to CO2 was
      measured in nine elderly untrained men (UT) [mean age 66.3 (SEM 3.1) years] and
      nine master athletes (MA) [mean age 62.7 (SEM 0.8) years] at rest, during
      moderate exercise (40% maximal oxygen uptake, VO2max), and during strenuous
      exercise (70% VO2max) using the rebreathing method. Our results showed that the
      ventilation response to CO2 did not differ with endurance training and/or
      exercise, that the threshold of the CO2 response (Th) increased with exercise (P
      < 0.001), that the increase in Th in MA was higher than in UT between rest and
      moderate exercise [deltaTh(0-40): 8.55 (SEM 1.8) vs 3.06 (SEM 1.72) mmHg, P <
      0.05], and that deltaTh(0-40) and Th during moderate exercise were negatively
      correlated with arterial O2 saturation during maximal exercise (r=0.50, P<O0.05).
      We concluded therefore that exercise-induced hypoxaemia in master athletes may
      not be due to a lower ventilation response to CO2, but may be partly related to a
      greater increase in Th during moderate exercise.

PMID- 9562364
TI  - Body composition and isokinetic strength of professional Sumo wrestlers.
AB  - The purpose of this study was to investigate the profiles of body composition and
      force generation capability in professional Sumo wrestlers. The subjects were 23
      professional Sumo wrestlers [mean age 22.0 (SEM 1.2) years] including those
      ranked in the lower- (Jonokuchi, n=10), middle- (Sandanme, n=8) and higher
      division (Makuuchi, n=5), 22 weight-classified athletes [5 judo athletes, 5
      wrestlers, and 12 weight lifters, mean age 20.7 (SEM 0.7) years], and 21
      untrained men [mean age 20.1 (SEM 0.2) years]. In the Sumo wrestlers, body mass
      ranged between 77.0 and 150.0 kg, body mass index between 25.9 and 44.5 kg x m(
      2), relative fat mass (%FM) between 11.9 and 37.0%, and fat-free mass (FFM)
      between 59.1 and 107.6 kg. The Sumo wrestlers showed significantly higher %FM and
      smaller elbow and knee extensor cross-sectional areas (CSA) than the weight
      classified athletes who weighed from 90.4 kg to 133.2 kg. Moreover, isokinetic
      forces in the flexion and extension of elbow and knee joints, respectively, at
      three constant velocities of 1.05, 3.14 and 5.24 rad x s(-1) were significantly
      lower in the Sumo wrestlers than in the weight-classified athletes and untrained
      subjects when expressed per unit of body mass. However, the median value of FFM
      relative to body height in the higher-division Sumo wrestlers was ranked high in
      the range of magnitude among those reported previously in the literature for
      heavyweight athletes. Moreover, the results on the comparisons within the Sumo
      wrestlers showed that not only FFM but also force generation capability,
      expressed both as an absolute term and as a value relative to both body mass and
      muscle CSA, might be factors contributing to the performance of Sumo wrestlers.

PMID- 9562365
TI  - Effect of oral creatine ingestion on parameters of the work rate-time
      relationship and time to exhaustion in high-intensity cycling.
AB  - The relationship between work rate (W) and time to exhaustion (t) during intense
      exercise is commonly described by either a hyperbolic function (NLin), t= W'/(W
      Wcp), or by its linear equivalent (LinW) Wlim=W' + Wcp(t). The parameter Wcp
      (critical power) has been described as an inherent characteristic of the aerobic
      energy system, while W' has been shown to be a ralid estimate of anaerobic work
      capacity. Recent studies have demonstrated that oral supplementation of creatine
      monohydrate (CrH2O) increases total muscle creatine stores, and have linked these
      increases to improved performances in intense intermittent exercise. This study
      was conducted to determine the effect of CrH2O supplementation on estimates of W'
      and Wcp derived from the NLin and LinW equations, and to determine the effect of
      CrH2O on t in exhaustive constant power exercise of different intensities.
      Fifteen active but untrained university students completed three phases of
      testing on a cycle ergometer: (1) familiarization, three learning trials, (2)
      baseline determination of W' and Wcp, four bouts performed at a W selected to
      elicit fatigue in 90-600 s, and (3) experimental determination of W' and Wcp,
      four bouts performed at the same W as baseline, but performed after 5 days of
      ingesting either a placebo (4 x 6 g of glucose/day) or CrH2O (4 x 5 g of CrH2O
      and 1 g glucose/day). Testing was administered in a double-blind manner. Analyses
      of covariance revealed a significant effect for CrH2O on both estimates of W'
      (NLin, P=0.04; LinW, P < 0.01), but not on estimates of Wcp (NLin, P=0.37; LinW;
      P=0.30). Within groups, t was significantly different for only CrH2O at the two
      highest Ws (P=0.04). It is concluded that oral ingestion of CrH2O increases
      estimates of W' due to an improved t at the shorter, more intense exercise bouts.

PMID- 9562366
TI  - Running economy deteriorates following 60 min of exercise at 80% VO2max.
AB  - Fifteen young adult Singaporean male physical education students maximum oxygen
      consumption [(VO2max) = 56 (4.7) ml x kg(-1) min(-1)] performed three prolonged
      runs in a counterbalanced design. The running bouts varied in time (40 vs 60 min)
      and intensity (70% vs 80% VO2max). Each prolonged run was separated by 7 days.
      The running economy (RE) at 10.8 km x h(-1) during 10-min running bouts was
      measured before (RE1) and after (RE2) each prolonged run. A control study
      involved monitoring RE at 10.8 km x h(-1) before and after 60 min rest. There
      were no differences between RE1 and RE2 values during the control run. However,
      there were differences between RE1 and RE2 values when separated by a prolonged
      run. For example, the mean (SD) changes in oxygen consumption (ml x kg(-1) x min[
      1]) values were 38.2 (2.5) versus 40.1 (2.6) (40 min at 80% VO2max), 38.9 (2.8)
      versus 41.5 [2.6] (60 min at 70% VO2max), and 39.0 (3.1) versus 42.7 (2.9) (60
      min at 80% V02max; P < 0.01). The results of this investigation support the
      hypothesis that RE deteriorates during prolonged running, and that the magnitude
      of the deterioration in RE increases with both increasing exercise intensity and
      duration.

PMID- 9562367
TI  - Adaptations in rat skeletal muscle following long-term resistance exercise
      training.
AB  - The purpose of this investigation was to determine whether long-term, heavy
      resistance training would cause adaptations in rat skeletal muscle structure and
      function. Ten male Wistar rats (3 weeks old) were trained to climb a 40-cm
      vertical ladder (4 days/week) while carrying progressively heavier loads secured
      to their tails. After 26 weeks of training the rats were capable of lifting up to
      800 g or 140% of their individual body mass for four sets of 12-15 repetitions
      per session. No difference in body mass was observed between the trained rats and
      age-matched sedentary control rats. Absolute and relative heart mass were greater
      in trained rats than control rats. When expressed relative to body mass, the mass
      of the extensor digitorum longus (EDL) and soleus muscles was greater in trained
      rats than control rats. No difference in absolute muscle mass or maximum force
      producing capacity was evident in either the EDL or soleus muscles after
      training, although both muscles exhibited an increased resistance to fatigue.
      Individual fibre hypertrophy was evident in all four skeletal muscles
      investigated, i.e. EDL, soleus, plantaris and rectus femoris muscles of trained
      rats, but muscle fibre type proportions within each of the muscles tested
      remained unchanged. Despite an increased ability of the rats to lift
      progressively heavier loads, this heavy resistance training model did not induce
      gross muscle hypertrophy nor did it increase the force-producing capacity of the
      EDL or soleus muscles.

PMID- 9562368
TI  - Motor unit activity during long-lasting intermittent muscle contractions in
      humans.
AB  - Changes accompanying long-lasting intermittent muscle contractions (30%-50% of
      the maximal) were investigated by tracing the activity of 38 motor units (MU) of
      the human biceps brachii muscle recorded from fine-wire branched electrodes. The
      motor task was a continuous repetition of ramp-and-hold cycles of isometric
      flexion contractions. During ramp-up phases a significant decline in recruitment
      thresholds was found with no changes in the discharge pattern. During ramp-down
      phases the unchanged mean value of derecruitment thresholds during the task was
      accompanied by increased duration of the last two interspike intervals (ISI).
      These findings would suggest that during fatigue development the main
      compensatory mechanism during ramp-up contractions is space coding while for ramp
      down contractions it is rate coding. During the steady-state phases the mean
      value of ISI, as well as the firing variability. had increased by the end of the
      task in most of the MU investigated . In addition 17 recruited MU were also
      investigated. These units revealed a lower initial discharge rate and a faster
      decrease in the mean discharge rate with the development of fatigue. The gradual
      reduction of the recruitment threshold of already active MU and the recruitment
      of new units demonstrated an increased excitability of the motorneuron pool
      during fatigue. A typical recruitment pattern (a first short ISI followed by a
      long one) was observed during ramp-up contractions in units active from the very
      beginning of the task, as well as during sustained contractions at the onset of
      the stable discharge of the additionally recruited MU.

PMID- 9562369
TI  - Human energy expenditure when walking on a moving platform.
AB  - The assumption that working on board ship is more strenuous than comparable work
      ashore was investigated in this study. Various physiological parameters (VO2,
      VCO2, VE and HR) have been measured to determine the energy expenditure of
      subjects walking slowly on a moving platform (ship motion simulator). Twelve
      subjects (eight men and four women) walked either freely on the floor or on a
      treadmill at a speed of 1 m x s(-1). Platform motion was either in a heave, pitch
      or roll mode. These three conditions were compared with a control condition in
      which the platform remained stationary. The results showed that during pitch and
      roll movements of the platform, the energy expenditure for the same walking task
      was about 30% higher than under the stationary control condition (3.6 J x kg[-1]
      x m[-1] vs 2.5 J x kg[-1] x m[-1], P < 0.05) for both walking on a treadmill and
      free walking. The heart rate data supported the higher energy expenditure results
      with an elevation of the heart rate (112 beats x min[-1] vs 103 beats x min[-1],
      P < 0.05). The heave condition did not differ significantly from the stationary
      control condition. Pitch and roll were not significantly different from each
      other. During all experimental conditions free walking resulted in a higher
      energy cost of walking than treadmill walking (3.5 J x kg[-1] x m[-1] vs 2.7 J x
      kg[-1] x m[-1], P < 0.05) at the same average speed. The results of this
      experiment were interpreted as indicating that the muscular effort, needed for
      maintaining balance when walking on a pitching or rolling platform, resulted in a
      significantly higher work load than similar walking on a stable or a heaving
      floor, independent of the mode of walking. These results explain in part the
      increased fatigue observed when a task is performed on a moving platform.

PMID- 9562370
TI  - IL-6 antisense oligonucleotides inhibit IgE production in IL-4 and anti-CD40
      stimulated human B-lymphocytes.
AB  - Stimulation of tonsillar B-lymphocytes with CD40 antibodies and IL-4 leads to
      homotypic adhesion, proliferation, and differentiation into Ig-producing cells.
      It also leads to the production of IL-6, a pleiotropic cytokine involved in B
      cell maturation and differentiation. To assess the importance of IL-6 in the
      differentiation process, an antisense oligonucleotide to IL-6 was added to
      tonsillar B-cells together with CD40 antibodies and IL-4. This led to clearly
      reduced levels of IL-6 as well as to a specific inhibition of IgE production.
      Also, IgG secretion was somewhat reduced while IgM appeared to be unaffected. The
      effects were not due to toxicity of the oligonucleotide since proliferation
      proceeded normally or was slightly enhanced in the presence of the antisense. The
      findings show that endogenous IL-6 is an important co-factor for the generation
      of B-cells secreting IgE and IgG but that it is not required for IgM production.
      They further indicate that IL-6 may not be necessary as a co-factor in CD40/IL-4
      induced proliferation.

PMID- 9562371
TI  - Prevention of lung eosinophilic inflammation by oral tolerance.
AB  - Airway inflammation plays a major role in human asthma. Increasing evidence
      points to a close correlation between eosinophil infiltration and allergic lung
      disease. A new murine model of eosinophilic lung inflammation has recently been
      developed; it consists of immunizing mice with small fragments of solidified hen
      egg white implanted (EWI) into the subcutaneous tissue. In this model, which is
      further characterized here, mice challenged with ovalbumin (OVA) present an
      intense and persistent lung eosinophilia, as well as histopathological findings
      that resemble human asthma. In the present work, the effect of oral tolerance on
      the development of allergic lung inflammation in B6 mice immunized with antigen
      plus adjuvant or with EWI is investigated. It was found that in mice rendered
      orally tolerant by previous exposure to antigen in the drinking water, the T
      helper type 2 cell (Th2)-associated allergic responses in both protocols of
      immunization were almost completely abolished. The allergic responses were
      assessed by pulmonary and bone marrow eosinophilia, lung histopathology and
      antigen-specific IgE and IgG1 production. These findings provide the first
      indication that Th2-associated lung pathology can be prevented by oral tolerance.

PMID- 9562372
TI  - Peptide transport in human lymphoblastoid and tumor cells: effect of transporter
      associated with antigen presentation (TAP) polymorphism.
AB  - CD8+ T-cells recognize antigenic peptides presented by major histocompatibility
      complex (MHC) class I molecules. These peptides bind to MHC class I molecules in
      the endoplasmic reticulum (ER) lumen. Antigenic peptides are translocated from
      the cytosol to the lumen of ER by transporter associated with antigen
      presentation (TAP) proteins. In this study, it is shown that TAP1 polymorphism
      influences the peptide substrate specificity in human B-lymphoblastoid and tumor
      cell lines. TAP1A and 1C alleles specifically enhance translocation of model
      peptides containing basic C-terminal amino acid residue. However, TAP1B allele
      does not show specificity for the peptide C-terminus. Human basophilic leukemia
      (Ku812), and hepatocellular carcinoma (PLC/PRF/5) cells express TAP1 molecules
      and exhibit TAP-mediated allele-specific peptide uptake after gamma-interferon
      (gamma-IFN) treatment. Ku812 cells express TAP1A and preferentially take up
      antigenic peptides with a basic C-terminus, however, PLC/PRF/5 cells with the
      TAP1B allele take up low but equivalent levels of peptides regardless of basic,
      acidic, or hydrophobic C-termini. Moreover, TAP2 polymorphisms have no influence
      on the peptide translocation in normal or tumor cell lines. In addition, Daudi, a
      beta2-microglobulin (beta2m) deficient human Burkitt lymphoma, cell line also
      showed TAP-dependent peptide uptake. Taken together, these results suggest that
      human TAP1 but not TAP2 polymorphisms influence the antigenic peptide transport
      and that this transport is independent of beta2m in this system.

PMID- 9562373
TI  - Characterisation of two human dendritic cell-lines that express CD1a, take-up,
      process and present soluble antigens and induce MLR.
AB  - Dendritic cells (DC) are bone marrow derived cells present in diverse tissues and
      organs including the skin, mucosae and blood. DC have a capital role in the
      afferent pathway of the immune response because of its role in up-take,
      processing and presenting antigens to immune cells. Human DC are usually
      identified by the expression of surface CD1a and HLA-DR. Despite the significant
      recent developments for in vitro generation of DC derived from blood by using
      cytokines like GM-CSF and IL-4, the studies on DC and specially on human
      Langerhans cells (LC) have been hampered by the laborious isolation procedure and
      the small yield of cells obtained by the various methods of isolation used so
      far. Therefore, a priority has been a search for monoclonal dendritic cell-lines
      with LC characteristics in order to facilitate the research in this area. The
      present study reports on the generation of two stable, self-replicant, adherent,
      dendritic, CD1a+, HLA-DR , CD45RO , CD23/FcERII+ cell-lines that up-take and
      process soluble antigens but also inducing MLR and antigen-dependent T-cell
      response.

PMID- 9562374
TI  - Co-stimulation of human peripheral blood mononuclear cells with IL-2 and anti-CD3
      monoclonal antibodies induces phosphorylation of CREB.
AB  - Phosphorylation of the cAMP-response element binding protein CREB within 1 h of
      CD2 but not CD3 cross-linking of human PBMC was recently demonstrated. The
      absence of P-CREB following CD3 cross-linking was unexpected, as other
      laboratories reported increased phosphorylation of CREB following CD3 cross
      linking of the Jurkat lymphocyte cell line. Due to Jurkat T-cells being IL-2
      independent, it was postulated that IL-2 might provide a necessary co-stimulus
      for phosphorylation of CREB in primary lymphocytes. Therefore, P-CREB was
      evaluated following co-stimulation of human PBMC through the IL-2 and CD2 or CD3
      receptors. IL-2 did not further augment phosphorylation of CREB following CD2
      cross-linking. However, while neither IL-2 nor CD3 cross-linking alone induced P
      CREB, a 4.5-fold increase in phosphorylation of CREB within 1 h of IL-2/CD3 co
      stimulation was observed. Phosphorylation was not associated with the induction
      of cAMP, and inhibition of PKA signaling had no effect on P-CREB. Consistent with
      signal transduction through p56lck or p59fyn, inhibition of PTK signaling reduced
      phosphorylation 50%. Interestingly, inhibiting PKC signaling with calphostin C
      further increased P-CREB levels 3-fold over that observed in IL-2/CD3 co
      stimulated cells not pretreated with a PKC inhibitor. In contrast to previous
      studies performed in the absence of exogenous IL-2, no increase in binding of
      CREB to a 32P-labeled oligonucleotide probe was observed by electrophoretic
      mobility shift assay. These data suggest that the IL-2 and CD3 signaling pathways
      provide a necessary and co-operative stimulus promoting phosphorylation of CREB
      following receptor cross-linking.

PMID- 9562375
TI  - Altered receptor expression and decreased sensitivity of T-cells to the
      stimulatory cytokines IL-2, IL-7 and IL-12 in HIV infection.
AB  - A dysregulated production of regulatory cytokines has been proposed as a
      determinant in the progression of HIV infection. The sensitivity of T-cells to
      these cytokines has, however, not fully been investigated. Therefore, the
      responses of PBMC and T-cell subsets to the stimulatory cytokines IL-2, IL-7 and
      IL-12 in HIV-infected patients and HIV-negative controls were compared by
      examining their effect on the production of secondary cytokines (IFNgamma, IL-4
      and IL-10), by simultaneous determination of T-cell activation and apoptosis and
      by measuring cytokine receptor expression. Production of IFNgamma was decreased
      in PBMC from the patients after stimulation with several combinations of
      stimulatory cytokines. IL-10 was only induced upon stimulation with IL-2 and IL
      12 and tended to be produced more in patients. Expression of the different
      cytokine receptor chains showed complex alterations in HIV+ patients as compared
      to controls. The most pronounced changes were decreased expression of both IL
      2Ralpha and IL-7Ralpha chain on CD8+ T-cells and an increase of IL-12Rbeta on
      both T-cell subsets from the patients. Evaluation of CD25 upregulation and blast
      formation revealed a deficient response to all three stimulatory cytokines in
      CD8+ but not in CD4+ T-cells from patients as compared to controls. Both CD4+ and
      CD8+ T-cells from the patients were less sensitive to the anti-apoptotic effect
      of IL-7 whereas only CD8+ T-cells were less sensitive to the anti-apoptotic
      effect of IL-2. The present data show that CD8+ T-cells, and to a lesser extent
      CD4+ T-cells, become less sensitive to IL-2, IL-7 and IL-12 during HIV infection.
      The decreased capacity of T-cells to respond to these cytokines could contribute
      to the HIV-related immune dysfunction.

PMID- 9562376
TI  - Deoxyspergualin neither counteracts lipopolysaccharide (LPS) or Staphylococcus
      aureus enterotoxin-B (SEB) induced lethality in mice nor does it modulate the
      release of tumor necrosis factor-alpha.
AB  - To gain further insights into the immunopharmacological mode of action of the
      immunosuppressant antibiotic deoxyspergualin (DSP), its effects were evaluated in
      murine lethal endo- and exotoxemia. These are two cytokine-mediated macrophage
      and T cell dependent immunoinflammatory conditions that can be induced in D
      Galactosamine (D-Gal) presensitized mice by the injections with either LPS or
      SEB, respectively. The results show that prophylactic treatment with DSP (2.5 or
      5 mg/kg bd.wt. 48, 24 and 2 h prior to challenge) neither improved the rate of
      survival, nor influenced the massive increase in the blood levels of tumor
      necrosis factor-alpha which followed the challenge with LPS or SEB. In sharp
      contrast, these clinical and seroimmunological events were both markedly
      counteracted by prophylactic treatment with sodium fusidate, another
      immunosuppressive agent used as control.

PMID- 9562377
TI  - The role of calnexin in NK-target cell interaction.
AB  - In this study, a relationship between target cell sensitivity to natural killing
      and target cell expression of the molecular chaperone++ calnexin was assessed.
      The NK-resistant cell line NKR was originally derived from the NK-sensitive,
      human T-cell line CEM and does not synthesize calnexin protein or mRNA. The cell
      lines CEM, NKR and 1B9 (NKR transfected with a calnexin cDNA) were compared in a
      number of assays. All the lines but CEM were resistant to NK in conventional 4 h
      cytotoxicity assay, but were highly sensitive to IL-2 activated NK. Incubation of
      NK cells with CEM but not with the other two lines led to increased expression of
      the NK cell activation marker CD69. Treatment of effector cells with PGE2 and TGF
      beta resulted in an inhibition of NK activity and CD69 expression. The calnexin
      transfected clone 1B9 clone had intermediate ability to block cytotoxicity in
      cold target inhibition assay compared to CEM and NKR. Expression of the adhesion
      molecules CD44 and LFA-1alpha was significantly higher on both calnexin positive
      cell lines compared to NKR. These data suggest that calnexin controls the
      expression of some, but not all, target structures that are necessary for binding
      and activation of NK cells.

PMID- 9562378
TI  - Identification of target cells by immunohistochemical detection of covalently
      rearranged estradiol in rehydrated paraffin sections.
AB  - Estradiol is released from the binding niche of the receptor and covalently
      arrested in the molecular vicinity by the Mannich reaction during target fixation
      in acetic acid/formaldehyde. The exposed steroid is freely accessible for
      appropriate antibodies. It can be visualized in sections by the second
      antibody/enzyme technique in high resolution and without enhancements.

PMID- 9562379
TI  - Immunocytochemical studies on endothelin in mast cells and macrophages in the rat
      gastrointestinal tract.
AB  - To reveal the distribution of endothelin (ET)-containing stromal cells (mast
      cells and macrophages), we investigated the rat gastrointestinal tract
      immunohistochemically using antibodies to Big ET-1, Big ET-2, Big ET-3, and
      mature ETs. In all the regions of the gastrointestinal tract, immunoreactivity
      for all the antibodies used was found in stromal cells that were located mainly
      in the lamina propria (not in the submucosa). The number of these cells was
      largest in the small intestine and smallest in the colon. Moreover, Big ET-2,
      which was originally identified in the gastrointestinal tract, was also found in
      many stromal cells, but Big ET-3-containing cells, unexpectedly, were found in
      almost the same number as Big ET-2-containing cells, while Big ET-1-containing
      cells were few. These immunopositive stromal cells seemed to be mast cells and
      macrophages from their histological features. Double-immunohistochemical staining
      revealed that 92% of the mature ETs-positive cells were mast cells; the rest were
      macrophages. Furthermore, we confirmed that mature ETs coexisted with ET-A or ET
      B receptors in identical cells. Hence, we presume that ETs are synthesized in and
      secreted from stromal cells in the rat gastrointestinal tract, that their main
      isotypes are not only ET-2 but also ET-3, and that ETs may act in an
      autocrine/paracrine fashion.

PMID- 9562380
TI  - A specific and sensitive double-immunofluorescence method for the demonstration
      of S-antigen and serotonin in trout and rat pinealocytes by means of primary
      antibodies from the same donor species.
AB  - Immunocytochemical double-labeling methods are important tools in cell and
      neurobiology. Here we describe a method which is based on double
      immunofluorescence and allows specific detection of two different antigens
      located in the same cell compartment by two primary antibodies raised in the same
      species. As an example, we present the double-immunolabeling method for the S
      antigen (SAg), a photoreceptor-specific protein, and the indoleamine serotonin
      (5HT) in dissociated trout and rat pineal cells immobilized on coverslipped and
      in frozen sections of the trout pineal organ. As a first step, the preparations
      on the slides or coverslips were sequentially incubated with the first primary
      antibody (rabbit anti-SAg), the fluorescein-labeled (anti-rabbit) secondary
      antibody, and then with normal rabbit serum. Meanwhile, the second primary
      antibody (rabbit anti-5HT) was coupled to a Cy3-labeled secondary (anti-rabbit)
      antibody in a reaction tube and excess binding sites were quenched with normal
      rabbit serum. This complex was applied to the specimens after completion of the
      first (SAg) immunoreaction on the slide. For control experiments, the first (anti
      SAg) or the second (anti-5HT) primary antibody were omitted. Most of the rat and
      trout pinealocytes were double immunolabeled for SAg and 5HT. In the trout, few
      cells contained SAg or 5HT immunoreaction only. This underlines the selectivity
      of each immunoreaction. The results show that the method can be used for the
      analysis of whole cells and tissue sections by means of conventional fluorescence
      and confocal laser scanning microscopy.

PMID- 9562381
TI  - Guided migration as a novel mechanism of capillary network remodeling is
      regulated by basic fibroblast growth factor.
AB  - To investigate mechanisms of capillary network remodeling, we developed a serum
      free angiogenesis in vitro system in three-dimensional fibrin matrices which
      allows the study of directional growth of endothelial sprouts, anastomosis, and
      remodeling ('pruning') of the primitive plexus toward more elaborated capillary
      trees. To follow the movements of living endothelial cells by inverse
      fluorescence microscopy, we cocultured unlabeled endothelial cells with
      endothelial cells labeled with the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate (DiI). We show that elongation and
      retraction of neighboring capillary sprouts occurs simultaneously, resembling a
      tug-of-war by which endothelial cells are withdrawn from shortening sprouts to
      become incorporated in other sprouts nearby. For the first time, we directly
      demonstrate the long-suspected parallel sliding movement of endothelial cells. We
      show that cell migration persists within immature capillaries even after sprouts
      have merged to continuous capillary loops, leading to overlapping growth of
      opposing sprout tips. As a novel concept of capillary remodeling, we distinguish
      two types of endothelial cell migration: sprouting and guided migration.
      Sprouting is the de novo invasion of a matrix by endothelial cells, and guided
      migration is the locomotion of cells along preexistent capillary-like structures.
      We show that guided migration leads to remodeling of immature capillary networks
      and to the retraction of sprouts. We describe a method for quantification of
      sprouting versus guided migration in DiI-mosaic-labeled capillary networks, and
      we present evidence that endothelial cell-derived basic fibroblast growth factor
      serves as a chemotactic signal for other cells to migrate along a preestablished
      capillary-like structure.

PMID- 9562382
TI  - Characterization of the cells in the repair tissue of full-thickness articular
      cartilage defects.
AB  - It is well established that a full-thickness articular cartilage defect is
      repaired with a fibrocartilaginous tissue, cells of which are derived from
      undifferentiated mesenchymal stem cells in the bone marrow. To characterize the
      repair cells biochemically, full-thickness defects were created in rabbit knee
      joints and the repair tissues taken at 3, 6, and 12 weeks after surgery. The
      repair cells were cultured and examined biochemically to investigate the effects
      of four exogenous growth factors with regard to the metabolism of type II
      collagen and proteoglycans. A significant increase of carboxy-terminal type II
      procollagen peptide production was observed in the conditional medium of the
      repair cells, especially taken at 6 weeks after surgery, in the presence of each
      growth factor. Glycosaminoglycan content was also increased and proteoglycan
      synthesis stimulated. The repair cells taken at the early stage of the repair
      process could originally have more activity of type II collagen synthesis, and
      the growth factors used could enhance the differentiation of the repair cells in
      vitro.

PMID- 9562383
TI  - Differential expression of IFN-gamma, IL-4, IL-10, and IL-1beta mRNAs in
      decalcified tissue sections of mouse lipopolysaccharide-induced periodontitis
      mandibles assessed by in situ hybridization.
AB  - To examine the role of T cell subgroups, Th1 and Th2, in the development of
      periodontitis, the expression of various cytokines was investigated in a mouse
      model of alveolar bone resorption using in situ hybridization (ISH) with
      digoxigenin-labeled oligonucleotides. When mice received repetitive injections
      with Escherichia coli lipopolysaccharide into the gingiva every 48 h, alveolar
      bone resorption was detectable after the fourth injection, reaching a maximum
      after the 13th injection. For the best performance of ISH, we first had to choose
      a decalcification protocol. Among various decalcification protocols, 10% EDTA (4
      degrees C, 5-6 days) was the best for 28S rRNA staining. Positive cells for
      transcripts of interferon-gamma (Th1 product) were detected after the fourth
      injection, reaching a maximum after the tenth injection. A similar pattern was
      obtained for interleukin (IL)-10 mRNA (Th2 product) and IL-1beta, while the
      positive cell number reached a maximum after the 13th and 10th injections,
      respectively. The number of IL-4 mRNA (Th2 product)-positive cells remained low
      till the tenth injection, but increased thereafter. Consequently, we found that
      the population change from Th1 to Th2 in the inflammation site correlated with
      the transition from gingivitis to periodontitis, indicating differential roles of
      T cell subgroups in the development of periodontitis.

PMID- 9562384
TI  - Platelet-derived growth factor-B induces transformation of fibrocytes into
      spindle-shaped myofibroblasts in vivo.
AB  - Platelet-derived growth factor (PDGF) has a targeted activity on mesenchymal
      cells, but the in vivo effects of PDGF are not well understood. We have applied
      about 3 microg of PDGF-A and PDGF-B on the differentiated chorioallantoic
      membrane (CAM) of 13-day-old chick embryos. After 1-3 days, specimens were
      evaluated macroscopically, histologically with semi- and ultrathin sections, and
      immunohistologically with antibodies against smooth muscle alpha-actin
      (alphaSMA), desmin, and fibronectin (FN). Proliferation studies were performed
      according to the 5-bromo-2-deoxyuridine (BrdU)/anti-BrdU method. We did not
      observe effects of PDGF-A. PDGF-B induced proliferation of fibrocytes and their
      transformation into myofibroblasts. Bundles of spindle-shaped myofibroblasts
      accumulated beneath the chorionic epithelium. These cells were strongly positive
      for alphaSMA and FN, but negative for desmin. They possessed a well developed
      rough endoplasmic reticulum and bundles of microfilaments anchoring in the cell
      membrane. Our results suggest that PDGF-B is a "transforming" growth factor with
      important functions during formation of granulation tissue which are closely
      comparable to the effects of the PDGF-B-like protein of simian sarcoma virus.
      PDGF-B also induced vascular alterations in the CAM, which, however, appeared to
      be a secondary effect. While the intra-chorionic capillaries were lost, an
      accumulation of small vessels positive for alphaSMA was observed. This indicates
      a function for PDGF-B during segregation of main vessels from a primary vascular
      plexus.

PMID- 9562385
TI  - Class II MHC-expressing cells in the rat adrenal gland defined by monoclonal
      antibodies.
AB  - The detailed distribution and heterogeneity of various immunocompetent cells were
      characterized in the normal adrenal gland of the rat, with special emphasis on
      major histocompatibility complex (MHC) class II-expressing cells and macrophages.
      All adrenals contained at least two different populations of cells reactive with
      the dendritic cell or the macrophage antibodies. These cells were clearly
      distinguished from adrenal parenchymal cells by their morphology and location.
      The majority of dendritic cells were immunoreactive for the MHC class II (Ia)
      antigen (MRC OX6) and/or the dendritic cell antibodies (MRC OX62), and negative
      for the macrophage antibodies (ED1, ED2, and/or MRC OX42), whereas the main
      population of macrophages was immunonegative for the former antibodies and
      positive for the latter. The OX62-positive cells and the OX42-labeled cells
      occurred exclusively throughout the medulla. The cellular density of dendritic
      cells in the adrenal cortex was significantly higher than that of macrophages.
      Double-immunoperoxidase staining for ED1 and OX6 revealed that positively stained
      cells could be classified into the following categories: ED1+OX6+, ED1+OX6-, and
      ED1-OX6+. More then 40% of OX6+ cells were immunoreactive for ED1 in the zona
      glomerulosa, while approximately 15%, 20%, and 30% of OX6+ cells were positive
      for ED1 in the zona fasciculata, zona reticularis and medulla, respectively.
      ED1+ED2- cells were more frequently detected in the zona glomerulosa than in
      other adrenal zones. Only a few ED1-ED2+ cells were located in the zona
      glomerulosa, whereas a large number of them were found in the zona fasciculata.
      In the zona reticularis and medulla, ED1+ED2+, ED1+ED2-, and ED1-ED2+ cells were
      detected in the ratio 2:1:3. Our rsults suggest that dendritic cells and
      macrophages mature during their migration within the adrenal gland. These
      immunocompetent cells may contribute to a paracrine regulation of adrenal
      function under physiological conditions.

PMID- 9562386
TI  - Contribution of carbon monoxide-producing cells in the gastric mucosa of rat and
      monkey.
AB  - Recent studies have shown that carbon monoxide (CO) may function as a gaseous
      signaling molecule in a similar way to nitric oxide. In the gastrointestinal
      tract, immunoreactivity against a CO-producing enzyme, heme oxygenase-2 (HO-2),
      was reported in epithelial cells and neurons of submucosal and myenteric plexus.
      However, details of the epithelial cells in the gastric mucosa remain unknown.
      The aim of this study was to clarify if mRNA for HO-2 is expressed in the rat
      stomach, if HO-2 protein is present in the mucosa, and to define the cell types
      of the HO-2-immunoreactive cells. HO-2 mRNA and protein were detected in fundic
      and pyloric mucosa of rat stomach using an RNA protection assay and western blot
      analysis. Immunohistochemical study showed that HO-2 was localized in parietal
      cells of the fundic glands and gastrin cells of the pyloric glands of both rat
      and monkey. The results suggest that HO-2 enzyme is produced in the gastric
      mucosa, and that CO is released from parietal cells and gastrin cells.

PMID- 9562387
TI  - Extralysosomal localisation of acid phosphatase in the rat kidney.
AB  - There is strong evidence that acid phosphatase (AcPase) plays an important role
      in the catabolism of the glomerular basement membrane (GBM) and the removal of
      macromolecular debris resulting from ultrafiltration. Recent enzyme histochemical
      investigations provide new evidence of the antithrombotic and anti-inflammatory
      function of ADPase and on the distribution of AcPase in mouse kidney tubule
      cells. By means of 3 mM cerium as the trapping agent and 1 mM p-nitrophenyl
      phosphate as the substrate, extralysosomal AcPase could be demonstrated at the
      ultrastructural level. Following a mild perfusion fixation (2% formaldehyde +
      0.07% glutaraldehyde), an effective postfixation and short enzyme incubations (20
      min) with microwave irradiation, highly specific enzyme histochemical reaction
      product and reasonable structural preservation were obtained. Extralysosomal,
      membrane-bound AcPase was observed along the endoplasmic reticulum, the trans
      Golgi cisternae, the nuclear envelope, basal infoldings of the proximal and
      distal tubular cells and on glomerular profiles, e.g. cell membranes of
      podocytes, endothelium and basement membrane. Large amounts of extralysosomal
      AcPase were observed in the basement membrane of glomeruli, in contrast to no
      AcPase activity in the tubular and mesangial basement membrane. The observed
      difference in AcPase activity in the tubular epithelial basement membrane and the
      GBM supports the idea that AcPase in GBM specifically serves in the clearance of
      macromolecular debris to facilitate ultrafiltration. In the GBM a laminar
      distribution is observed, suggesting that both epithelial and endothelial cells
      are involved in the production of AcPase.

PMID- 9562388
TI  - Testicular expression of the mouse histone H1.1 gene.
AB  - The replication-dependent H1 histone subtype H1.1 is the predominant H1 histone
      subtype in germ cell chromatin during early spermatogenesis. H1.1 gene
      transcription was assigned by in situ hybridization with H1.1-specific RNA probes
      to the basal layer of germ cells within the seminiferous tubule, but not to the
      somatic cells of the testis. In situ hybridization and immunohistochemistry with
      testis from 5-, 9-, and 20-day-old mice showed that H1.1 mRNA and protein was
      already present in spermatogonia of the prepuberal testis. In testis from 20-day
      old and adult mice, the H1.1 mRNA remained confined to the most peripheral layer
      of germ cells. In contrast to the H1.1 mRNA, the H1.1 protein persisted in the
      germ cell chromatin with decreasing concentration throughout meiosis and in
      postmeiotic cells. These data demonstrate that in situ hybridization with H1.1
      mRNA-specific probes can serve to identify germ cells with ongoing DNA
      replication. Comparison of results obtained from in situ hybridization and
      immunocytochemistry indicates that the period of H1.1 gene transcription is
      restricted to the proliferative phase in which cells undergo successive
      divisions, whereas the H1.1 protein is a component of the proliferative, meiotic,
      and spermiogenic phases.

PMID- 9562389
TI  - Neuraminidase injected into the cerebrospinal fluid impairs the assembly of the
      glycoproteins secreted by the subcommissural organ preventing the formation of
      Reissner's fiber.
AB  - Neuraminidase was injected into the cerebrospinal fluid of normal rats to
      investigate the assembly and fate of the desialylated Reissner's fiber
      glycoproteins. It was established that a single injection of neuraminidase
      cleaved the sialic acid residues of the Reissner's fiber glycoproteins that had
      been assembled before the injection, and of the molecules that were released over
      a period of at least 4 h after the injection. These desialylated glycoproteins
      underwent an abnormal assembly that led to the formation of spheres instead of a
      fiber. The number of these spheres increased during the 4-h period following the
      injection, indicating that neuraminidase did not prevent the secretion of the
      Reissner's fiber glycoproteins into the cerebrospinal fluid. The spheres remained
      attached to the surface of the subcommissural organ and became intermingled with
      infiltrating cells, many of which were immunocytochemically identified as
      macrophages. The latter were seen to contain immunoreactive Reissner's fiber
      material. It is concluded that the desialylated Reissner's fiber glycoproteins
      forming the spheres underwent an in situ degradation by macrophages, thus
      resembling the normal process undergone by the Reissner's fiber glycoproteins
      reaching the massa caudalis.

PMID- 9562390
TI  - Histochemical analysis of sialic acids in the epididymis of the rat.
AB  - A variety of sialic acids contained in the rat epididymis were histochemically
      examined by means of lectin and pre-lectin methods by light microscopy.
      Epididymides from adult male Sprague-Dawley rats were fixed in Bouin's fluid and
      routinely embedded in paraffin wax. Hydrated sections were subjected either to
      the lectin methods using biotinylated Limax flavus, Sambucus nigra, Sambucus
      sieboldiana or Maackia amurensis lectins or to the selective periodate oxidation
      phenylhydrazine-thiocarbohydrazide-silver protein-physical development technique
      with or without saponification. The present results revealed that principal cells
      in the initial segment and caput contain sialic acid linked to alpha2,6
      galactose/N-acetylgalactosamine, whereas those in the corpus and cauda include
      the sialic acid alpha2,3-galactose sequence. Narrow and clear cells involve all
      the types of sialic acids examined. Basal and halo cells mainly contain sialic
      acid alpha2,3-galactose. 8- And/or 9-O-acetylated sialic acids were predominantly
      distributed in principal cells of the initial segment and proximal caput. These
      findings are taken to indicate that various sialic acids in the epididymis could
      participate in different physiological functions characteristic of the regions in
      this organ.

PMID- 9562391
TI  - Close anatomical relationships between nerve fibers and MHC class II-expressing
      dendritic cells in the rat liver and extrahepatic bile duct.
AB  - The anatomical relationships between immunocytochemically identified nerve fibers
      and MHC class II-expressing antigen presenting dendritic cells were investigated
      in the rat hepatobiliary system using immunocytochemistry, confocal laser
      scanning, and electron microscopy. Close proximity of nerve fiber varicosities
      immunostained for PGP 9.5 and MHC class II-expressing dendritic cells was
      frequently observed in the wall of extrahepatic bile ducts, in Glisson's area,
      around central and hepatic veins, and in the liver capsule. Contacts between
      nerve fibers staining for substance P, calcitonin gene-related peptide,
      calretinin, and vasoactive intestinal polypeptide and dendritic cells were more
      often observed around extrahepatic bile ducts than in Glisson's area. Nerve
      fibers immunostaining for tyrosine hydroxylase and neuropeptide Y were numerous
      both in the wall of extrahepatic bile ducts and in Glisson's area and frequently
      contacted dendritic cells there. At the ultrastructural level, close membrane
      contacts between bare axolemmal areas of unmyelinated nerve fibers and processes
      of MHC class II-expressing cells were observed. These results demonstrate close
      anatomical relationships of nerve fibers from various sources with antigen
      presenting dendritic cells in the visceral domain and suggest modulation of
      antigen presentation by the autonomic nervous system.

PMID- 9562392
TI  - Topography of growth hormone receptor expression in the bovine embryo.
AB  - Using in situ hybridization, mRNA encoding the growth hormone receptor (GHR) was
      localized in preimplantation embryos produced by in vitro fertilization (IVF) as
      well as in 30- to 70-day-old bovine embryos. In IVF embryos the transcript of GHR
      was demonstrated in the inner cell mass of 8-day-old blastocysts. In 30-day-old
      embryos, the mesonephros was the first organ to express the mRNA of GHR. In 40
      day-old embryos, the transcript was found in the neurones of the spinal
      ganglions, the splanchnic nerves and the motoneurones of the spinal cord, in the
      vascular endothelium, and in the developing striated muscle tissue.
      Colocalization of the protein by immunohistochemistry showed an identical
      distribution pattern of GHR in 30- to 70-day-old embryos.

PMID- 9562393
TI  - Cancer registries in environmental cancer epidemiology.

PMID- 9562394
TI  - Environmental risk factors of breast cancer.
AB  - Breast cancer is women's most ubiquitous cancer. The role of dietary factors is
      controversial, but there is limited evidence for such occupational risk factors
      as employment in the pharmaceutical industry and as a beautician. Ionizing
      radiation probably increases the risk. Exposure to chlorinated hydrocarbon
      pesticides, chlorinated solvents, and polychlorinated biphenyls may be risk
      factors, although the evidence is insufficient. Data on low-frequency
      electromagnetic fields are inconclusive. Tobacco smoking may be a risk factor,
      but the effect may depend on N-acetyltransferase 2 genetic polymorphisms. There
      are yet unidentified determinants, probably environmental, that may act via
      estrogenic activity or through other mechanisms. The etiology may vary according
      to the joint estrogen and progesterone receptor status of the tumor. P53 mutation
      frequency varies considerably in breast cancer populations, which may reflect
      variation in exogenous exposures. Epidemiology research on breast cancer needs to
      consider subtypes of the disease, lifetime exposure assessment, host
      susceptibility, and adjustment for reproductive and menstrual history.

PMID- 9562395
TI  - Exposure to motor vehicle exhaust and childhood cancer.
AB  - OBJECTIVES: A case-referent study was conducted to test the hypothesis that
      exposure to motor vehicle exhaust increases the risk of childhood cancer.
      METHODS: Data from a study of residential magnetic field exposure and childhood
      cancer were used. From a population of 127000 children living within 300 m of
      transmission lines in Sweden, 142 cases of childhood cancer were identified,
      including 39 cases of leukemia and 33 cases of central nervous system tumor.
      Approximately 4 referents per case were selected at random from the study base.
      The nitrogen dioxide content of the outdoor air was estimated as an indicator of
      motor vehicle exhaust. The applied methods give the 99th percentile of the
      nitrogen dioxide content of the outdoor air for 1-h averages over 1 year.
      RESULTS: A relative risk estimate of 2.7 [95% confidence interval (95% CI) 0.9
      8.5] was found for total cancer at exposure levels of > or = 50 microg/m3,
      related to those with < or = 39 microg/m3. At > or = 80 microg/m3, the relative
      risk was estimated at 3.8 (95% CI 1.2-12.1). Elevated, but imprecise risk
      estimates were found for leukemia and central nervous system tumors. CONCLUSIONS:
      The results indicate an association between childhood cancer and motor vehicle
      exhaust, although the number of cases was small. These findings and the results
      of previous studies suggest that further studies of the association between motor
      vehicle exhaust and childhood cancer are warranted.

PMID- 9562396
TI  - Mortality from asthma and cancer among sulfite mill workers.
AB  - OBJECTIVES: The aims of the present case-referent study were to investigate
      whether sulfite workers show increased mortality from asthma, chronic obstructive
      pulmonary disease or certain malignancies of interest in relation to sulfite mill
      work. The main exposure from the pulping processes is from sulfur dioxide, wood
      dust and terpenes. METHODS: The subjects of the study were all the men who died
      between 1960 and 1989 and who were aged 40 to 75 years at death (N = 780) in the
      parishes surrounding 3 sulfite mills. The men who died from asthma (N = 13), COPD
      (N = 20), lung cancer (N = 33), stomach cancer (N = 35), or brain tumor (N = 10)
      formed the case group. All the subjects, except the cases in question, were used
      as referents. As a proxy variable of exposure, job titles from the registers of
      deaths and burials were used, and 24% of the subjects were classified as exposed.
      RESULTS: There was an increased mortality from asthma [odds ratio(OR) 2.8, 90%
      confidence interval (90% CI) 1.1-6.8] and brain tumors (OR 3.3, 90% CI 1.2-8.9)
      among the sulfite workers. The mortality due to lung cancer was not significantly
      increased (OR 1.4, 90% CI 0.7-2.6), and there was a reduced mortality from
      stomach cancer (OR 0.4, 90% CI 0.2-0.9). CONCLUSIONS: The increased asthma
      mortality may be due to accidental exposure to irritating gases, such as sulfur
      dioxide. The increased risk for brain tumors has no obvious explanation.

PMID- 9562397
TI  - Effects of long-term organophosphate exposures on neurological symptoms,
      vibration sense and tremor among South African farm workers.
AB  - OBJECTIVES: This study assessed the relationship between long-term exposure to
      organophosphate insecticides and neurological symptoms, vibration sense, and
      motor tremor after control for the effect of past poisoning and acute exposure.
      METHODS: This cross-sectional study included 164 pesticide applicators and 83
      nonspraying reference workers on deciduous fruit farms. The workers were tested
      on the Vibratron II, on tests of dynamic and static tremor, and for a set of
      neurological and "dummy" symptoms. Exposure was derived with the use of a job
      exposure matrix for pesticides in agriculture. RESULTS: Compared with
      nonapplicators, current applicators reported significantly more dizziness,
      sleepiness, and headache and had a higher overall neurological symptom score.
      This association remained statistically significant after multiple logistic
      regression analyses controlling for a range of confounders and effect modifiers
      [odds ratio (OR) 2.25, for current applicators having high neurological score,
      95% confidence interval (95% CI) 1.15-4.39]. The average lifetime intensity of
      organophosphate exposure was nonsignificantly associated with both neurological
      (OR 1.98, 95% CI 0.49-7.94) and "dummy" symptoms (OR 2.37, 95% CI 0.54-10.35).
      Previous pesticide poisoning was significantly associated with the neurological
      scores (OR 4.08, 95% CI 1.48-11.22) but not with the "dummy" symptoms. Vibration
      sense outcomes were associated with age and height, but not with the
      organophosphate exposure measures. In the multiple linear regression modeling for
      tremor intensity in the dominant hand, recent organophosphate exposure in the
      past 10 days was a significant predictor (partial correlation coefficient =
      0.04), but none of the long-term organophosphate exposure measures were
      significant. CONCLUSIONS: Strong evidence was found for an association between
      symptom outcomes and past organophosphate poisoning and between symptom outcomes
      and current spray activity. In contrast to symptoms, there was no association
      between either past poisoning or current spray activity and vibration sense or
      tremor outcome. Long-term organophosphate exposure did not appear to predict
      symptoms, vibration sense, or tremor outcome.

PMID- 9562398
TI  - Metabolic interaction between toluene, trichloroethylene and n-hexane in humans.
AB  - OBJECTIVES: This human experimental study describes the mutual metabolic
      interaction between toluene, trichloroethylene, and n-hexane. METHODS: Eight
      healthy male volunteers were exposed to combinations of toluene (1.5 or 4
      mg/min), trichloroethylene (1.5 or 4 mg/min), and n-hexane (0.3 or 1.0 mg/min)
      for 60 min. End exhaled air concentrations were measured before and up to 240 min
      after the start of exposure. The urinary excretion of hippuric acid, o-cresol,
      trichloroethanol, trichloroacetic acid, and 2,5-hexanedione was measured before
      and up to 270 min after the start of the exposures. RESULTS: When the low dose
      rates were combined, the end exhaled concentrations were at or below the
      detection limit, while an increase in the dose rate of toluene increased the area
      under the end exhaled air concentration curve (AUC) of toluene,
      trichloroethylene, and n-hexane by factors of 44 (16-117) [geometric mean and 95%
      confidence interval], 12.8 (4.1-40.0), and 2.2 (1.2-4.1), respectively.
      Trichloroethylene, in turn, increased the AUC 5.0 (1.9-13.4), 25.8 (8.2-80.8) and
      2.9 (1.6-5.4), respectively, whereas the corresponding values for n-hexane were
      1.9 (0.7-5.1), 1.5 (0.5-4.6), and 3.2 (1.8-5.9). An 18 (range 2-34)% decrease in
      hippuric acid was the only interaction measured in the metabolite excretion. No
      correlation occurred between the individual measures of the end exhaled
      concentrations or the excretion of metabolites. CONCLUSIONS: The study shows that
      the threshold for the flow-limited metabolism of the 3 solvents in humans is
      exceeded at liver dose rates corresponding to inhalation exposure at occupational
      exposure limits. At these levels there are metabolic interactions between the 3
      solvents.

PMID- 9562399
TI  - Lead concentrations in tibial and calcaneal bone in relation to the history of
      occupational lead exposure.
AB  - OBJECTIVES: This study tested a simple model of the relationship between the lead
      concentration in bone (bone-Pb), exposure time, and lead in plasma (P-Pb) and
      whole blood (B-Pb) to make it possible to use bone-Pb as a retrospective exposure
      index. METHODS: Seventy-seven active lead workers and 24 referents were studied.
      The bone-Pb in tibia (T-Pb) and calcaneus (C-Pb) was measured by in vivo X-ray
      fluorescence. P-Pb was calculated from B-Pb by use of the nonlinear relationship
      between these variables. Cumulative B-Pb (cumB-Pb) and P-Pb (cumP-Pb) were
      calculated to the time of the bone-Pb measurements. In addition, cumP-Pb was
      adjusted by applying varying rate constants for the transfer of lead from bone to
      plasma. RESULTS: There were close linear associations between the lead
      concentrations in tibia (proportion of variance explained, R2 = 0.78) and
      calcaneus (R2 = 0.80), on one hand and the cumB-Pb on the other. The best fit of
      bone-Pb to the adjusted cumP-Pb (0.79 for T-Pb; 0.82 for C-Pb) was obtained for
      the terminal phase half-times of 13 and 12 years, respectively. CONCLUSIONS: The
      combined data on bone-Pb and exposure time make it possible to estimate previous
      mean P-Pb and B-Pb. Such estimates will be valuable in studies of toxic effects
      on long-term exposed lead workers when data on the intensity of previous exposure
      are lacking. The use of P-Pb in modeling bone-Pb kinetics is physiologically
      relevant, but the use of adjusted cumP-Pb, as compared with cumB-Pb, did not
      significantly change the variance in the relation to bone-Pb.

PMID- 9562400
TI  - Dementia and occupational exposure to magnetic fields.
AB  - OBJECTIVES: The purpose of the present report was to assess whether occupational
      magnetic field exposure is a risk factor for dementia, in particular for
      Alzheimer's disease. METHODS: Case-control analyses were applied to 77 dementia
      cases, 55 of whom had Alzheimer's disease, ascertained from the population-based
      Swedish twin register. Two reference groups were derived, with 228 and 238
      persons, respectively. Occupations were linked to a job-exposure matrix based on
      magnetic field measurements. Primary occupation, last occupation before reference
      date, and the occupation with the highest magnetic field exposure during the
      subject's lifetime were evaluated. RESULTS: For primary occupation, all relative
      risk estimates were close to unity. For last occupation, at the exposure level >
      or = 0.2 microT, a relative risk was found for dementia estimated at 3.3 [95%
      confidence interval (95% CI) 1.3-8.6] and 3.8 (95% CI 1.4-10.2) for reference
      groups 1 and 2, respectively. The relative risk for Alzheimer's disease was
      estimated at 2.4 (95% CI 0.8-6.9) and 2.7 (95% CI 0.9-7.8), respectively. For the
      occupation with the highest magnetic field exposure, the relative risk estimates
      were close to unity for reference group 1 and slightly elevated for reference
      group 2. The relative risk estimates were greater for the subjects who were
      younger at onset (< or =75 years). CONCLUSIONS: These results only partially
      support previous findings, but they indicate that occupational magnetic field
      exposure may possibly influence the development of dementia.

PMID- 9562401
TI  - Relationship of job strain and iso-strain to health status in a cohort of women
      in the United States.
AB  - OBJECTIVE: This study examined the relationships of job strain and iso-strain
      psychosocial work-environment exposures to health status in a cohort of working
      women in the United States. METHODS: In a cross-sectional survey, 33689 women
      responded to the Karasek job content and the MOS SF-36 health status
      questionnaires. The psychosocial work-environment exposures were characterized
      using the job strain and iso-strain frameworks. Health status was assessed with
      the following 6 scales: physical functioning, vitality, freedom from pain, mental
      health, role limitations due to physical health, and role limitations due to
      emotional health. RESULTS: When compared with active work, high-strain work (high
      job demands and low job control) was associated with lower vitality, mental
      health, higher pain, and increased risks of both physical and emotional role
      limitations. Iso-strain work (high strain and low work-related social support)
      increased the risks further. Job insecurity was also associated with lower health
      status. CONCLUSIONS: The analyses supported the hypothesis that the psychosocial
      work environment is an important determinant of health status among working
      women. The findings suggest that incorporating social conditions at work into the
      measurement of psychosocial work-environment exposure improves the identification
      of high-risk work arrangements.

PMID- 9562402
TI  - Computer mouse position as a determinant of posture, muscular load and perceived
      exertion.
AB  - OBJECTIVES: This study concerned the influence of 6 positions of the computer
      mouse on the work table on posture, muscular load, and perceived exertion during
      text editing. METHODS: An optoelectronic 3-dimensional motion analysis system was
      used to register the postures of 10 men and 10 women using video display units.
      Muscular load was also registered (with electromyography), as was perceived
      exertion (with rating scales). RESULTS: A neutral posture with a relaxed and
      supported arm showed the least perceived exertion, and the electromyographic
      results showed low activity in both trapezius muscles in this position. Short
      operators (all women) showed a numerically higher activity in the 4 examined
      muscles than the tall operators (all men, except 1). This finding could be
      related to lower muscle force among women and to anthropometric differences,
      which also influence biomechanic load moments. Narrow-shouldered operators (8
      women and 1 man) and short operators worked with larger outward rotation and
      abduction of the shoulder in a position of the mouse lateral to the keyboard than
      the broad-shouldered (7 men and 2 women) and tall operators did. Arm support
      markedly reduced muscle load in the neck-shoulder region among the operators.
      CONCLUSIONS: The operators using video display units in this study preferred to
      use the mouse on a table in a close to relaxed, neutral posture of the arm in
      combination with arm support. Short and narrow-shouldered operators worked in
      more strenuous postures of the arm when the mouse was located lateral to the
      keyboard.

PMID- 9562403
TI  - Sex ratio of offspring of residents of a highly polluted housing site.

PMID- 9562404
TI  - Work environment and health among Danish employees, 1990-1995.

PMID- 9562405
TI  - Pesticide hazards in Costa Rica and Kenya.

PMID- 9562406
TI  - In situ polymerase chain reaction amplification of HIV-1 DNA in brain tissue.
AB  - A direct in situ polymerase chain reaction (IS-PCR) assay is described for the
      detection of HIV-1 proviral DNA in formalin fixed paraffin embedded brain tissue.
      Biotin-16-dUTP is incorporated during the PCR process and microwave pretreatment
      of tissue sections ensures that no non-specific incorporation into damaged or
      nicked genomic DNA occurs. Two methods are compared to detect the biotinylated
      amplified product, the use of an avidin-biotin-alkaline phosphatase complex (ABC)
      and the application of tyramide signal amplification (TSA) which allows both
      chromogenic and fluorescence detection. TSA detection enhances the sensitivity of
      IS-PCR, permitting fewer PCR cycles and preserving tissue morphology.

PMID- 9562407
TI  - The use of a reverse transcription-polymerase chain reaction for the detection of
      viral nucleic acid in the diagnosis of Crimean-Congo haemorrhagic fever.
AB  - A reverse transcription-polymerase chain reaction (RT-PCR) was applied
      retrospectively to 80 stored serum samples from 45 confirmed Crimean-Congo
      haemorrhagic fever (CCHF) patients in southern Africa, and it was found that
      viral RNA could be detected in a proportion of samples up to day 16 of illness.
      Early in the disease there is relatively good correlation between the results
      obtained by RT-PCR and virus isolation, but after the first week it appears that
      infective virus is progressively cleared from serum while nucleic acid remains
      demonstrable in a proportion of patients well into convalescence. A further 47
      serum samples from 38 patients with suspected viral haemorrhagic fever, 19 of
      whom proved to be cases of CCHF, were tested prospectively on being received at
      the laboratory. The combined use of RT-PCR with ethidium bromide stained gels for
      the detection of viral RNA, plus indirect immunofluorescence for the detection of
      IgG and IgM antibodies to CCHF virus, permitted a presumptive diagnosis to be
      reported within 8 h of receiving the first specimen from 18/19 cases of the
      disease studied prospectively. The nineteenth case was confirmed within 48 h when
      antibody response was demonstrated in a second serum sample. Viral nucleic acid
      was not detected in serum samples from 19 patients in whom alternative diagnoses
      were established.

PMID- 9562408
TI  - Evaluation of 14 commercial HIV-1/HIV-2 antibody assays using serum panels of
      different geographical origin and clinical stage including a unique
      seroconversion panel.
AB  - The performance of 14 commercially available HIV-1/2 antibody assays were
      compared using well-characterized serum panels containing in total 1500 1800
      sera. The panels included consecutive HIV-negative blood donor sera from Sweden,
      unselected blood donor and patient sera from Tanzania and unselected sera from
      outpatient clinics in Guinea-Bissau. Furthermore selected HIV-1 antibody positive
      sera from Sweden and Tanzania and HIV-2 antibody positive sera from Guinea-Bissau
      were included in the panels. The HIV-1 antibody positive sera were from
      individuals at various stages of HIV infection, from primary infection, to
      asymptomatic phase and late stage disease. 12 of the 14 assays identified
      correctly all HIV-1 and HIV-2 antibody positive sera. One Tanzanian HIV-1
      antibody positive sample with complete banding pattern on Western blot was not
      detected by two of the ELISAs employing synthetic peptides. There were small
      differences in sensitivity between the assays when used for analysis of
      seroconversion panels. The most sensitive assay, Abbott IMx HIV-1/HIV-2 III Plus
      detected antibodies in all nine samples collected from four individuals during
      the first week after onset of symptoms of primary HIV-1 infection. Most of the
      assays became reactive during the second week after onset of symptoms and the
      least sensitive assays were reactive from the third week. The assays showed a
      high specificity ranging from 99.2 to 100% when used for analysis of Swedish
      blood donor sera, while most of the assays showed a significantly lower
      specificity, 91.9-99.6%, when used for testing African specimens.

PMID- 9562409
TI  - Diagnosis of human immunodeficiency virus infection by a polymerase chain
      reaction assay evaluated in patients harbouring strains of diverse geographical
      origin.
AB  - Since the development of the highly sensitive polymerase chain reaction, PCR has
      been increasingly used for the diagnosis of viral infections, including the
      detection of human immunodeficiency virus (HIV), the causative agent of AIDS. In
      our laboratory a diagnostic PCR is carried out on proviral HIV-1 DNA using a
      standardised algorithm based on three HIV-1 primer sets. The three primer sets,
      amplifying a fragment in the LTR-gag gene, in the pol gene and in the env gene,
      are situated within conserved regions of the HIV-1 genome. These primers allow us
      to detect not only HIV strains from Belgian patients but also from African
      patients, who are, for historical reasons, a substantial part of the HIV-positive
      patients in Belgium. We are able to detect 1-5 copies of proviral HIV-1 DNA with
      each of the three nested primer sets. A sensitivity and specificity of 92 and
      100%, respectively, were achieved when testing 24 Belgian and African HIV-1
      seropositive samples. In our lab, the same PCRs are also used for the detection
      of viral RNA in cases of a doubtful undetectable viral load when using a
      commercial HIV-1 viral load assay. This is because present-day commercial assays
      are not entirely reliable with divergent strains. Both our 'in-house' diagnostic
      DNA and RNA-PCR can also be used semiquantitatively with limiting dilutions.

PMID- 9562410
TI  - Detection of cytomegaloviral DNA in human milk cells and cell free milk whey by
      nested PCR.
AB  - Human cytomegalovirus (HCMV) DNA can be detected in different compartments of
      human milk. A protocol for the preparation of milk whey free of fat and cells for
      the detection of human cytomegalovirus (HCMV) by nested PCR is presented. This is
      based upon the experience of the separation of more than 200 milk specimens of
      healthy seropositive breast feeding mothers. HCMV DNA could be detected in
      freshly centrifuged and filtrated milk whey specimens without contamination by
      cellular DNA. In limiting dilution experiments using HCMV plasmid DNA, the effect
      of different DNA extraction procedures from native milk and milk whey on the
      detection limit of cytomegaloviral DNA was demonstrated. About 200 viral genome
      equivalents/ml in milk whey or native milk were detectable by classical organic
      phenol/chloroform extraction or a spin column method, respectively. The detection
      of viral DNA in milk cells depended on a minimum number of milk cells (10(5)-2 x
      10(5)) available for DNA extraction. In contrast to the findings of
      cytomegaloviral DNA in native sera or plasma of immunosuppressed patients we
      failed to amplify low level viral DNA from native breast milk by nested PCR due
      to an inhibition of Taq polymerase by lipid components. Finally, the course of
      cell associated and cell free DNAlactia was monitored. Analyzing sequential milk
      specimens, in some cases the presence of HCMV DNA in colostrum could be
      demonstrated. DNAlactia of milk cells and whey was partially discordant. Onset
      (week 1-4 after delivery) and duration (2 weeks up to more than 3 months) of
      DNAlactia showed distinct individual patterns. The methods described, allow
      further analysis of the mechanisms involved in the postnatal HCMV transmission by
      breast feeding seropositive mothers.

PMID- 9562411
TI  - Development of a syncytia inhibition assay for the detection of antibodies to
      bovine leukemia virus in naturally infected cattle; comparison with Western blot
      and agar gel immunodiffusion.
AB  - A syncytia inhibition assay (SIA) for the detection of antibodies to bovine
      leukemia virus is described. This test involves specific antibody-mediated
      inhibition of BLV-induced cytopathic effects in an indicator cell line. A total
      of 300 sera were screened commercially by agar gel immunodiffusion (AGID) and
      were then screened by Western blot and SIA. The new assay system provided results
      which were comparable to Western blot and AGID. The results obtained suggest that
      SIA may be more sensitive than either of the other two assay systems examined for
      the determination of the infection status of cattle.

PMID- 9562412
TI  - The MxA protein levels in whole blood lysates of patients with various viral
      infections.
AB  - Interferon alpha (IFNalpha), a type I interferon, can be considered as a viral
      infection marker because this cytokine is induced during many viral infections.
      However, it is quite difficult to detect IFNalpha in sera. Investigations are
      interested in various intra-cellular IFNalpha-induced proteins as viral infection
      markers. However the activity of these enzymes increased not only in response to
      type I IFNs but also to type II IFN. MxA protein can be detected in the cytoplasm
      of IFNalpha/beta-treated cells, whereas other cytokines, including IFNgamma, are
      poor inducers. Using an immunochemiluminescent assay, we studied MxA protein in
      whole blood of 34 patients with various viral infections. The whole blood was
      drawn into sterile vacuum tubes containing heparin or EDTA. MxA values were
      relatively similar in heparin-treated samples and EDTA-treated samples, with
      differences not exceeding 1 ng/ml. The levels of MxA protein were compared in
      whole blood obtained by using two different lysis procedures. A correlation was
      found between the MxA levels obtained by using procedure I and procedure II, but
      higher amounts of MxA protein were found with procedure II. The second procedure
      is rapid and more convenient than the other and it is carried out in one step
      which reduce technical problems. High levels of MxA protein were found in
      peripheral blood cells of patients with acute viral infections (Rotavirus,
      Adenovirus, RSV, CMV), but MxA protein was not elevated in bacterial infections.
      The MxA levels were also studied in peripheral blood of 32 HCV positive patients.
      MxA protein was not found in most of IFNalpha-untreated patients, even those with
      high viral load. In contrast, high levels of MxA protein were found in IFNalpha
      treated patients. MxA quantitation can be considered as a specific marker of
      acute viral infections, and could be useful in the management of treatment with
      IFNalpha.

PMID- 9562413
TI  - The use of DIG-labelled cRNA probes for the detection of cymbidium mosaic
      potexvirus (CymMV) and odontoglossum ringspot tobamovirus (ORSV) in orchids.
AB  - DIG-labelled sense and antisense cRNA probes were synthesized from cDNA clones of
      CymMV and ORSV for virus detection in infected plants. A slot-blot hybridization
      assay was developed using either crude leaf extracts or total RNA from infected
      leaves. The assay could detect 50 and 250 pg of purified CymMV and ORSV RNA,
      respectively. As little as 30 mg of Nicotiana benthamiana infected leaves was
      sufficient to provide positive detection. CymMV and ORSV were detected at 3125
      and 625 times dilution of leaf extracts, respectively. The DIG-labelled cRNA
      probes are stable for more than a year. This method is sensitive, reliable and
      suitable for large-scale routine testing of plant viruses. By using the two DIG
      labelled cRNA probes in situ, CymMV and ORSV were localized in systemically
      infected leaves and stems of N. benthamiana and orchids.

PMID- 9562414
TI  - Efficient cloning of cDNA from grapevine leafroll-associated virus 4 and
      demonstration of probe specificity by the viral antibody.
AB  - Using a random-PCR method, a cDNA clone (LR4) was constructed from the
      replicative form dsRNA of grapevine leafroll-associated virus 4 (GLRaV-4).
      Northern blot analysis showed hybridization of LR4 to dsRNA in an extract of a
      Thompson Seedless grapevine clone from which GLRaV-4 was isolated originally by
      Hu et al. (1990). The cDNA clone was sequenced and shown to be specific to GLRaV
      4 by reverse-transcription-PCR using GLRaV-4 particles enriched by the virus
      antibody coupled to magnetic beads. Reverse-transcription-PCR was used
      successfully to screen different varieties of grapevines for the virus. Western
      blot analysis of GLRaV-4 extracts from different varieties of infected grapevines
      revealed two distinct species of capsid protein with estimated Mr of either 35500
      or 38000 depending on the variety used. Both proteins reacted with polyclonal as
      well as monoclonal antibodies.

PMID- 9562416
TI  - Simple and rapid purification of alphaherpesviruses by chromatography on a cation
      exchange membrane.
AB  - A simple and rapid method is described for the purification of two
      alphaherpesviruses, pseudorabies virus (PrV) and bovine herpesvirus 1, by
      chromatography on a cation exchange membrane. Cell culture supernatants were
      passed over a sulfonic-acid modified filter membrane and virions were eluted with
      a potassium chloride-containing buffer. Over 85% of the virus was eluted within a
      single fraction and specific infectivity of the resulting virus preparation was
      over 10-fold higher than that of sucrose gradient-purified virions. Cation
      exchange was also used for purification of PrV mutants deleted in several
      glycoproteins which grow in cell culture to titers 10- to 100-fold lower than
      those obtained by wildtype PrV. For PrV, the presence of non-essential
      glycoprotein gC, which mediates interaction of virions with cell surface heparin
      sulfate during attachment, was crucial for the successful purification by cation
      exchange.

PMID- 9562415
TI  - Comparison of reverse transcription polymerase chain reaction, enzyme linked
      immunosorbent assay and virus isolation for the routine diagnosis of foot-and
      mouth disease.
AB  - A reverse transcription polymerase chain reaction (RT-PCR) method was compared
      with virus isolation in cell culture and the antigen detection ELISA for the
      primary diagnosis of foot-and-mouth disease (FMD) on 166 clinical samples from
      the field. Eighty samples were positive by virus isolation/ELISA and 78 by RT
      PCR. The RT-PCR detected FMD viral RNA in 11 of the 86 samples assessed as
      negative by virus isolation/ELISA but conversely failed to diagnose 13 samples
      identified as positive by the latter procedures. This RT-PCR is not serotype
      specific so a cDNA product is indicative of the presence of FMD viral RNA only.
      Confirmation of the specificity of the cDNA product and the identification of the
      serotype requires nucleotide sequence analysis. The value of the RT-PCR is that
      it can rapidly facilitate the molecular analysis of field isolates and thus
      provide important epidemiological information regarding the source of outbreaks.
      However, it is a sophisticated technique requiring specialised equipment,
      expertise and refined reagents and has to be used in conjunction with current
      procedures for FMD diagnosis.

PMID- 9562417
TI  - A novel method for pestivirus genotyping based on palindromic nucleotide
      substitutions in the 5'-untranslated region.
AB  - A simple and practical method was developed for pestivirus genotyping based on
      analysis of the secondary structures in the 5'-untranslated region (UTR). Three
      stable stem-loop structures, V1, V2 and V3, predicted by computer in the 5'-UTR,
      included strictly conserved consensus base-pairings which are shared by all the
      genotypes of pestivirus or are characteristic to each genotype of pestivirus. On
      the basis of the palindromic nucleotide substitution at the secondary structural
      level, six genotypes have been identified among pestivirus strains, irrespective
      of the cytopathic and non-cytopathic biotypes. They are genotypes Ia, Ib, Ic and
      II in bovine viral diarrhea virus, genotype III in border disease virus, and
      genotype IV in classical swine fever virus. The stable stem-loop structures,
      which were maintained by palindromic nucleotide substitutions in the stem region,
      may represent references for the classification and identification of pestivirus
      species and/or genotypes.

PMID- 9562418
TI  - Specific oligonucleotide primers for the direct detection of plum pox potyvirus
      cherry subgroup.
AB  - A specific polymerase chain reaction assay was developed for direct
      identification of the distinct subgroup of plum pox potyvirus (PPV) isolates from
      cherry trees (PPV-cherry, PPV-C) and its differentiation from other known
      subgroups of PPV. The specificity of the assay is based on using a pair of
      primers whose nucleotide sequences are located on the coat protein gene of PPV
      sour cherry (SoC) at regions of high nucleotide divergence between PPV-SoC and
      other isolates of PPV. The technique will be useful for studying the epidemiology
      of PPV-C as well as for practical testing in certification and quarantine
      programs worldwide.

PMID- 9562419
TI  - Leishmania amazonensis: the phagocytosis of amastigotes by macrophages.
AB  - In the present study, we examine the cell biology of Leishmania amastigote uptake
      by mammalian cells and compare this process to the phagocytosis of IgG-opsonized
      erythrocytes. We report that many aspects of amastigote uptake into macrophages
      resemble classical receptor-mediated phagocytosis. Parasite uptake requires
      energy expenditure by macrophages but not by parasites. Treating macrophages to
      prevent either energy metabolism or actin polymerization prevents amastigote
      uptake. The uptake of amastigotes by macrophages involves the colocalization of f
      actin, paxillin, and talin to phagocytic cups that are formed around amastigotes
      during internalization. Treatment of macrophages with genestein, to inhibit
      protein phosphorylation, prevents amastigote uptake, indicating that this
      process, like receptor-mediated phagocytosis, depends on protein tyrosine
      phosphorylation. However, the amount and the pattern of protein tyrosine
      phosphorylation observed during amastigote uptake by macrophages is reduced
      relative to that observed during IgG-erythrocyte phagocytosis. The uptake of
      viable, but not heat-killed amastigotes, is associated with a decrease in the
      intensity of several specific macrophage proteins that are phosphorylated on
      tyrosine residues. In summary, although many features of amastigote uptake by
      macrophages resemble classical receptor-mediated phagocytosis, differences in
      macrophage protein phosphorylation during amastigote phagocytosis may contribute
      to the unique aspects of amastigote uptake and intracellular survival in
      macrophages.

PMID- 9562420
TI  - Cellular and transcriptional changes during excystation of Giardia lamblia in
      vitro.
AB  - Excystation of Giardia lamblia entails differentiation of dormant cysts into
      parasitic trophozoites. Despite its importance for infection, this transformation
      is not understood at the cellular or molecular levels. In these studies, we
      report that excystation entails detection of environmental stimuli across the
      tough extracellular cyst wall leading to highly coordinated physiological,
      structural, and molecular responses. We found that novel cytoplasmic
      rearrangements and changes in individual species of mRNA and in cytoplasmic pH
      occur within the cyst wall in the earliest stage of excystation, in response to
      conditions modeling cyst ingestion and passage into the human stomach. This
      suggests that cysts do not contain all the mRNA needed for excystation and
      emergence and supports our hypothesis that external stimuli, including hydrogen
      ions, may penetrate or be perceived across the cyst wall. In contrast, changes in
      cyst wall structure or proteins were detected only later in excystation, in the
      stage that models passage into the human small intestine, where trophozoites can
      emerge and survive. These findings show that excystation of G. lamblia is a
      highly complex and active process and provide important insights into its
      cellular and molecular components.

PMID- 9562421
TI  - Plasmodium falciparum: characterization of organelle migration during merozoite
      morphogenesis in asexual malaria infections.
AB  - Treatment of asexual Plasmodium falciparum infections with the microtubule
      stabilizing agents Taxol or epothilone A prevents the depolymerization of nuclear
      microtubules. Serial thin sectioning of treated parasites revealed the presence
      of polymerized nuclear microtubule assemblies extending from spindle pole bodies
      into the forming merozoites in late stage infections. This organization prevented
      daughter merozoites from pinching off the mother schizont during merogony. An
      electron-dense collar was apparent at the junction of the budding parasites and
      the schizont plasma membrane, suggesting the presence of a contractile, actin
      myosin ring. Examination of Taxol or EpA arrested parasites provided new
      information about the merogonic process and the control of organelle migration.
      Drug treatment did not affect the migration or polarity of the rhoptries and
      micronemes. Ultrastructural characterization of drug-treated trophozoites
      identified an assembly of smooth vesicles and short tubules adjacent to the
      parasite nuclei. During merogony, these membranes were observed as flattened
      cisternae with dilated rims that appeared to be coated. The morphology and
      location of these membranes suggest that they may be the parasite Golgi
      apparatus. This investigation reveals that the antimalarial activity of
      microtubule stabilizing agents is due to their inhibition of merozoite formation.

PMID- 9562422
TI  - Characterization of an intracellular receptor for activated protein kinase C
      (RACK) from the mollusc Biomphalaria glabrata, the intermediate host for
      Schistosoma mansoni.
AB  - A receptor for activated protein kinase C (RACK) was characterized from the
      mollusc Biomphalaria glabrata, the intermediate host for the human parasite
      Schistosoma mansoni. This protein was shown to possess structural and functional
      characteristics of other RACK proteins from various cells and organisms. Its
      ability to bind mammalian PKCs also confirmed the conservation of PKC and RACK
      interactive domains throughout evolution. Results of immunolocalization indicated
      the presence of Bg RACK in the cytoplasm of mollusc hemocytes and B. glabrata
      embryonic (Bge) cells with a more intense staining around the nucleus. These
      results are in agreement with the association of RACK proteins with cytoskeletal
      elements.

PMID- 9562423
TI  - A novel member of the transforming growth factor-beta (TGF-beta) superfamily from
      the filarial nematodes Brugia malayi and B. pahangi.
AB  - Transforming growth factor-beta (TGF-beta) superfamily genes encode products
      controlling pattern formation, cell differentiation, and immune-mediated
      inflammation. Members of this superfamily are known in multicellular organisms
      from mammals to the model nematode Caenorhabditis elegans. Using PCR with
      oligonucleotides complementary to highly conserved motifs in the TGF-beta
      superfamily, we first isolated a genomic clone from the filarial nematode Brugia
      malayi. This gene, termed Bm-tgh-1 (TGF-beta homolog-1), spans 2.5 kb of genomic
      DNA and contains seven exons. Transcripts of this gene are poorly represented in
      cDNA libraries, but a full-length cDNA was isolated by RACE from B. pahangi (Bp
      tgh-1). The tgh-1 genes from the two species are >98% identical at the nucleotide
      and amino acid levels, differing at 18/1576 base pairs and 5/428 amino acids; all
      nonsynonymous substitutions are in the long N-terminal propeptide. They show a
      high level of similarity throughout all seven exons to a C. elegans gene on
      cosmid T25F10. Homology to other members of the TGF-beta superfamily is
      restricted to the C-terminal domain which contains the mature active protein. Key
      features shared with other members of the superfamily include the tetrabasic
      proteolytic cleavage site to release an active C-terminal peptide, seven
      cysteines arrayed in identical fashion, and conserved sequence motifs. tgh-1 is
      most similar to the BMP-1 subfamily involved in developmental signaling in
      nematodes, insects, and vertebrates. RT-PCR on first-strand cDNA from both Brugia
      species, with primers specific to the 3' end, showed that tgh-1 is not expressed
      in the microfilarial stage, but is detectable in the mosquito-derived infective
      larvae and is maximal in maturing parasites around the time of molting in the
      mammalian host. Adult parasites show a relatively low level of expression. The
      identification of tgh-1, and its preferential expression in developing parasites,
      suggests that it may be involved in key developmental events in the complex
      filarial life cycle.

PMID- 9562424
TI  - Plasmodium gallinaceum: effect of insect cells on ookinete development in vitro.
AB  - In vitro culture conditions affecting the transformation efficiency from zygote
      to ookinete for Plasmodium gallinaceum were examined, as a step toward improving
      the overall efficiency of in vitro culture systems for sporogonic stages.
      Gametocytes from infected chickens were allowed to fertilize in vitro and the
      resulting zygotes were purified and cultured. The time course for ookinete
      development in vitro was similar to that seen in Aedes aegypti mosquitoes.
      Supplementing a basal M-199 culture medium with heat-inactivated chicken serum
      and glucose did not affect transformation efficiency, but resulted in a four-fold
      increase in infectivity to mosquitoes when fed back to Ae. aegypti.
      Transformation from zygote to ookinete increased 5- to 10-fold when zygotes were
      cocultured with one of six different mosquito cell lines or a Drosophila cell
      line. Under optimal conditions, transformation efficiencies of up to 75% were
      observed. The presence of insect cells also increased the longevity of ookinetes
      in culture up to 42 h, while in acellular cultures ookinetes degenerated after
      about 24 h. The stimulatory effect was apparently not due to a factor secreted
      into the medium by the cells.

PMID- 9562426
TI  - Trypanosoma cruzi: immune response and functional heart damage induced in mice by
      the main linear B-cell epitope of parasite ribosomal P proteins.
AB  - We report herein on the specific and autoimmune humoral response generated by the
      immunization of mice with the R13 synthetic peptide coupled to a carrier protein,
      OVA. This peptide corresponds to the C-terminal region of Trypanosoma cruzi
      ribosomal P1 and P2 proteins (EEEDDDMGFGLFD), a sequence that differs from the
      other eukariotic P consensus sequence (EESDDDMGFGLFD) only in a nonconservative
      amino acid substitution. The antibody response studied by ELISA revealed that all
      R13-immunized mice had antibodies against R13, consisting mainly of IgG1 and IgG2
      isotypes, even though IgG3 and IgE isotypes were also observed. The self
      reactivity of anti-R13 sera assayed by immunoblot, revealed that all sera
      contained IgG antibodies binding to mouse and human 38-kDa heart antigen. This
      antigenic band binds several immunoglobulin isotypes (IgG2 > IgG3 > IgE > IgG1).
      The specificity of anti-R13 antibodies analyzed by competitive inhibition of R13
      ELISA using R13 and R7 (MGFGLFD) peptides revealed that the reactivity of the
      induced anti-P antibodies was not absorbed by R7. Therefore, the main immunogenic
      region of R13 for mouse would be EEEDDD, which contains the amino acid
      substitution. In parallel with this humoral response, both partial protection and
      heart damage were observed in R13-immunized mice. In fact, the R13-immunized mice
      showed significantly lower parasitemia and longer survival than the control
      animals. In addition, all R13-immunized mice showed electrocardiographic changes
      (bradycardia, prolonged PQ segment, and intraventricular conduction
      disturbances), which are typical findings in Chagas disease patients. This study
      represents the first definitive report in which one defined B-cell epitope, the
      single peptide R13 from T. cruzi, coupled to a carrier protein was able to induce
      specific and autoreactive antibodies as well as to generate heart functional
      alterations.

PMID- 9562425
TI  - Diethylcarbamazine (DEC) does not induce nitric oxide (NO) synthesis.
AB  - Diethylcarbamazine (DEC) was discovered in 1947 as a potent therapeutic agent in
      lymphatic filariasis and has been a mainstay of antifilarial therapy over the
      past five decades (R. I. Hewitt, et al., 1947, Journal of Laboratory and Clinical
      Medicine 32, 1304-1313). Several hundred million doses of this drug have been
      administered to people. Despite its widespread and successful use over this
      prolonged time scale, its mechanism of action remains obscure (R. M. Maizels and
      D. A. Denham, 1992, Parasitology 105 Suppl. 549-560). Numerous studies suggest
      that DEC has no direct effect on the parasite (F. Hawking and W. Laurie, 1949,
      Lancet 2, 146-147) and that it exerts its action by stimulating host immune
      defense mechanisms (F. Hawking et al., 1948, Lancet 2, 730-731), or by activating
      host platelets to become microfilaricidal (J. Y. Cesbron et al., 1987, Nature
      325(6104) 533-536). Recent data from two different laboratories suggest that NO
      may be involved in host defense against filarial parasites (T. V. Rajan et al.,
      1996, Infection and Immunity 64(8), 3351-3353; M. J. Taylor et al., 1996,
      Parasitology 112, 315-322). We investigated whether DEC stimulates the production
      of NO from murine macrophages or rat endothelial cells. DEC did not stimulate the
      synthesis or secretion of NO from either, nor did it synergize with interferon
      gamma or tumor necrosis factor-alpha in the induction of inducible NO synthase
      (iNOS). In addition, there was no consistent increase in the output of inorganic
      nitrate, the end product of NO metabolism, in the urines of rats treated with
      DEC. These data suggest that DEC does not achieve its therapeutic efficacy
      through the induction of host iNOS.

PMID- 9562427
TI  - Trypanosoma brucei: the dynamics of calcium movement between the cytosol,
      nucleus, and mitochondrion of intact cells.
AB  - Targeted aequorins (CYT-AEQ, NUC-AEQ, and MT-AEQ) were used to measure Ca2+
      concentrations within organelles of live trypanosomes. We determined that the
      nuclear envelope is a slight barrier to the free diffusion of Ca2+. This
      situation was especially evident when Ca2+ influx across the plasma membrane was
      stimulated with 200 nM melittin ([Ca2+]cyt = 1.2 +/- 0.4 microM and [Ca2+]nuc =
      0.85 +/- 0.15 microM). By contrast, the ionophores nigericin (2.7 microM) or
      monensin (2 microg/ml) were used to induce Ca2+ efflux from the acidic storage
      compartment. Small transient elevations in [Ca2+]cyt were observed (peaking at
      660 +/- 200 and 580 +/- 120 nM, respectively). Parallel and equivalent changes in
      [Ca2+1]nuc were recorded. Active accumulation of Ca2+ into the nucleus was not
      observed. Nigericin or monensin did not disrupt mitochondrial Ca2+ transport in
      vivo. Instead, the mitochondrion actively sequestered large quantities of Ca2+ in
      the presence of these ionophores, with peak values of 2.7 +/- 1.4 and 4.4 +/- 1.1
      microM, respectively. Overall, these data demonstrate that significant quantities
      of Ca2+ enter the nucleus following influx across the plasma membrane or
      following efflux from an intracellular acidic storage compartment. However, the
      magnitude of change for [Ca2+]cyt and [Ca2+]nuc is small compared to the total
      amount of exchangeable Ca2+ since the majority of released Ca2+ is actively
      sequestered by the mitochondrion.

PMID- 9562428
TI  - YIGSR is the preferential laminin-1 residing adhesion sequence for Trichomonas
      vaginalis.

PMID- 9562429
TI  - Plasmodium falciparum: a microassay for the malarial carbamoyl phosphate
      synthetase.

PMID- 9562430
TI  - A highly conserved large molecular weight cyclophilin of filarial parasites.

PMID- 9562431
TI  - Plasmodium falciparum: import of a phosphate carrier protein into heterologous
      mitochondria.

PMID- 9562432
TI  - Trypanosoma brucei brucei: characterization of an ODC null bloodstream form
      mutant and the action of alpha-difluoromethylornithine.
AB  - Ornithine decarboxylase (ODC) is a key enzyme in the polyamine synthesis pathway
      in African trypanosomes. We report here the characterization of an ODC null
      bloodstream form Trypanosoma brucei brucei mutant, created by replacing the ODC
      gene with antibiotic resistant marker genes through transfection and homologous
      recombination. The null mutant expresses no ODC mRNA or protein and does not have
      ODC enzymatic activity. We tested the attenuation of the bloodstream form ODC-
      mutants in mice, and showed that these mutants cannot multiply and are quickly
      cleared from the blood. We also tested the effect of DFMO on this ODC null
      mutant.

PMID- 9562433
TI  - Inactivation of voltage-gated cardiac K+ channels.
AB  - Inactivation is the process by which an open channel enters a stable
      nonconducting conformation after a depolarizing change in membrane potential.
      Inactivation is a widespread property of many different types of voltage-gated
      ion channels. Recent advances in the molecular biology of K+ channels have
      elucidated two mechanistically distinct types of inactivation, N-type and C-type.
      N-type inactivation involves occlusion of the intracellular mouth of the pore
      through binding of a short segment of residues at the extreme N-terminal. In
      contrast to this "tethered ball" mechanism of N-type inactivation, C-type
      inactivation involves movement of conserved core domain residues that result in
      closure of the external mouth of the pore. Although C-type inactivation can show
      rapid kinetics that approach those observed for N-type inactivation, it is often
      thought of as a slowly developing and slowly recovering process. Current models
      of C-type inactivation also suggest that this process involves a relatively
      localized change in conformation of residues near the external mouth of the
      permeation pathway. The rate of C-type inactivation and recovery can be strongly
      influenced by other factors, such as N-type inactivation, drug binding, and
      changes in [K+]o. These interactions make C-type inactivation an important
      biophysical process in determining such physiologically important properties as
      refractoriness and drug binding. C-type inactivation is currently viewed as
      arising from small-scale rearrangements at the external mouth of the pore. This
      review will examine the multiplicity of interactions of C-type inactivation with
      N-terminal-mediated inactivation and drug binding that suggest that our current
      view of C-type inactivation is incomplete. This review will suggest that C-type
      inactivation must involve larger-scale movements of transmembrane-spanning
      domains and that such movements contribute to the diversity of kinetic properties
      observed for C-type inactivation.

PMID- 9562434
TI  - Cytoskeletal role in the transition from compensated to decompensated hypertrophy
      during adult canine left ventricular pressure overloading.
AB  - Increased microtubule density causes cardiocyte contractile dysfunction in right
      ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and
      contractile abnormalities persist and progress during the transition to failure.
      Although more severe in cells from failing than hypertrophied RVs, the mechanical
      defects are normalized in each case by microtubule depolymerization. To define
      the role of increased microtubule density in left ventricular (LV) pressure
      overload hypertrophy and failure, in a given LV we examined ventricular
      mechanics, sarcomere mechanics, and free tubulin and microtubule levels in
      control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and
      with initially compensated hypertrophy that had progressed to LV muscle failure.
      In comparing initial values with those at study 8 weeks later, dogs with
      hypertrophy alone had a very substantial increase in LV mass but preservation of
      a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy
      and associated failure had a substantial but lesser increase in LV mass and a
      reduction in ejection fraction, as well as a marked increase in mean systolic
      wall stress. Cardiocyte contractile function was equivalent, and unaffected by
      microtubule depolymerization, in cells from control LVs and those with
      compensated hypertrophy. In contrast, cardiocyte contractile function in cells
      from failing LVs was quite depressed but was normalized by microtubule
      depolymerization. Microtubules were increased only in failing LVs. These
      contractile and cytoskeletal changes, when assayed longitudinally in a given dog
      by biopsy, appeared in failing ventricles only when wall stress began to increase
      and function began to decrease. Thus, the microtubule-based cardiocyte
      contractile dysfunction characteristic of pressure-hypertrophied myocardium,
      originally described in the RV, obtains equally in the LV but is shown here to
      have a specific association with increased wall stress.

PMID- 9562435
TI  - Cardiac graft intercellular adhesion molecule-1 (ICAM-1) and interleukin-1
      expression mediate primary isograft failure and induction of ICAM-1 in organs
      remote from the site of transplantation.
AB  - During the first few hours after heart transplantation, the occurrence of graft
      failure is unpredictable and devastating. An explosive cascade of inflammatory
      events within the reperfused graft vasculature is likely to be mediated, at least
      in part, by the local expression of the leukocyte adhesion receptor intercellular
      adhesion molecule-1 (ICAM-1, CD54). Furthermore, although proinflammatory
      cytokines such as interleukin-1 (IL-1) are known to autoinduce their own (and
      ICAM-1) expression in vitro, there are no data to identify their functional in
      vivo cross talk in the setting of isograft transplantation. To determine the role
      of ICAM-1 in primary graft failure, we used an isogeneic vascularized model of
      heterotopic cardiac transplantation. ICAM-1 mRNA and protein increased in grafts
      during the early posttransplant period and were predominantly localized in the
      endothelium. The functional significance of this was established using donor
      hearts obtained from either ICAM-1-deficient (ICAM-1 -/-) or control (ICAM-1 +/+)
      mice. ICAM-1 +/+ grafts exhibited increased neutrophil infiltration, reduced left
      ventricular compliance, and poorer survival than did ICAM-1 -/- grafts. Increased
      ICAM-1 expression was not limited to ICAM-1 +/+ grafts but also occurred in
      unmanipulated recipient organs located remote from the site of surgery (but only
      after transplantation of ICAM-1 +/+, not ICAM-1 -/-, cardiac grafts). This
      expression of ICAM-1 in remote organs appeared to be triggered by IL-1alpha
      released from the graft, because (1) in situ hybridization revealed increased IL
      1 mRNA within cells of the reperfused graft, including myocytes and endothelial
      cells; (2) ICAM-1 expression in remote organs coincided with a significant
      increase in serum levels of IL-1alpha after transplantation of ICAM-1 +/+ grafts;
      both remote organ ICAM-1 expression and IL-1alpha levels were blunted by
      implantation of ICAM-1 -/- grafts; and (3) remote organ ICAM-1 expression and
      neutrophil infiltration and IL-1 levels could be blocked by the administration of
      an IL-1 receptor antagonist. These data demonstrate an apparent positive-feedback
      loop in which local ICAM-1 and IL-1 expression leads to a mutual amplification of
      each other's expression within the reperfused graft, promulgating inflammatory
      events that are likely to be an important cause of primary cardiac graft failure.
      Because IL-1 receptor blockade reduces the IL-1-mediated autoinduction of IL-1,
      reduces the expression of ICAM-1 in both the graft and remote organs, and
      improves graft survival, it may provide a new and effective strategy to prevent
      the occurrence of primary cardiac graft failure.

PMID- 9562436
TI  - Hypertrophy, pathology, and molecular markers of cardiac pathogenesis.
AB  - Increased ventricular expression of several genes, including atrial natriuretic
      factor (ANF), has been documented in experimental models of cardiac hypertrophy.
      It remains to be clarified whether altered expression of these genes is a
      consistent marker of the hypertrophy itself or a marker of some parallel
      pathogenetic process. Using a transgenic mouse model of hypertrophic
      cardiomyopathy as a tool, we assessed the relationship between the amount of
      ventricular ANF gene expression and the degree of hypertrophy as well as the
      relationship between the cells expressing ANF and tissue pathology. We determined
      that hypertrophy is not always associated with increased ventricular expression
      of ANF and that cells expressing ANF are found in regions of tissue pathology. We
      propose that alteration in the ventricular expression of this gene is a sensitive
      indicator of cardiac pathogenesis and may result from a number of different
      stimuli that include, among others, abnormal tissue architecture and hemodynamic
      load.

PMID- 9562437
TI  - Acute pressure overload could induce hypertrophic responses in the heart of
      angiotensin II type 1a knockout mice.
AB  - Increasing evidence has suggested that locally produced angiotensin II (Ang II)
      plays an important role in the development of cardiac hypertrophy through the Ang
      II type 1 receptor (AT1). We and others have recently reported that Ang II is
      critical for mechanical stress-induced hypertrophic responses in vitro. Using
      AT1a knockout (KO) mice, we examined whether Ang II is indispensable for pressure
      overload-induced cardiac hypertrophy in the present study. Reverse-transcriptase
      polymerase chain reaction analysis revealed that AT1 mRNA levels were <10% in the
      heart of KO mice compared with wild-type (WT) mice, but the Ang II type 2
      receptor gene was expressed at almost the same levels in the hearts of both mice.
      Intravenous infusion of subpressor dose of Ang II induced c-fos gene expression
      in the hearts of WT mice but not KO mice. Acute pressure overload, however,
      induced expressions of immediate-early response genes and activations of mitogen
      activated protein kinases in the hearts of KO mice as well as WT mice. Both basal
      and activated levels of all these responses were significantly higher in KO mice
      than in WT mice. Pressure overload markedly increased the heart weight-to-body
      weight ratio in both mice strains at 14 days after aortic banding. These results
      suggest that acute hypertrophic responses could be induced by pressure overload
      in the in vivo heart without AT1 signaling.

PMID- 9562438
TI  - Regulation of vascular connexin43 gene expression by mechanical loads.
AB  - Vascular tissues respond to changes in the mechanical forces imposed on them with
      changes in vasomotor tone in the short term and with structural remodeling in the
      long term. Since these responses involve intercellular communication, we have
      investigated regulation of the gap junction proteins, connexin26 (Cx26),
      connexin37 (Cx37), connexin40 (Cx40), and connexin43 (Cx43), by mechanical loads.
      Results were compared with parallel experiments on c-fos and GAPDH. Twenty
      percent stretch of cultured vascular smooth muscle cells caused a 3-fold increase
      in Cx43 mRNA levels by 2 hours. Cx26 was expressed at low levels but failed to
      respond to stretch, and Cx37 and Cx40 were not detected. c-fos mRNA levels
      increased after 30 minutes of stretch, whereas GAPDH mRNA did not change. Protein
      levels of Cx43 increased by 4 hours and remained elevated for 16 hours. Nuclear
      run-on experiments confirmed that Cx43 and c-fos were transcriptionally regulated
      by stretch. New protein synthesis was not a requirement for the stretch-induced
      rise in Cx43 expression, since mRNA levels were unaffected by treatment with
      cycloheximide. To examine transcriptional control of Cx43, stretched and
      unstretched vascular smooth muscle cells were transfected with a variety of
      promoter-reporter gene constructs. Cx43 sequences extending from within exon 1
      (+162) to -1686 in the 5'-flanking region were coupled to the chloramphenicol
      acetyl transferase reporter gene. Deletions from the 5' end of these sequences
      differentially regulated reporter gene expression and indicated multiple
      potential regulatory sites. In particular, a putative activator protein-1 site at
      the -42 to -48 region was required for basal reporter activity. None of the
      promoter constructs revealed stretch sensitivity, indicating that the site of
      transcriptional control by stretch lies outside the -1686 to +162 region.
      Finally, Cx43 mRNA levels were assessed in cultured endothelial cells subjected
      to laminar shear stress of 15 dynes/cm2. Cx43 mRNA levels increased by
      approximately 4-fold at 1 hour and remained elevated for the duration of shear
      force. In conclusion, both mechanical strain and fluid shear stress caused
      increased expression of the gap junction protein Cx43.

PMID- 9562439
TI  - Fluid shear stress increases the production of granulocyte-macrophage colony
      stimulating factor by endothelial cells via mRNA stabilization.
AB  - To investigate whether the production of colony-stimulating factors (CSFs) by
      vascular endothelial cells is regulated by hemodynamic force, we exposed cultured
      human umbilical vein endothelial cells (HUVECs) to controlled levels of shear
      stress in a flow-loading apparatus and examined changes in the production of CSFs
      at both the protein and mRNA level. Exposure of HUVECs to a shear stress of 15
      and 25 dyne/cm2 markedly increased the release of granulocyte-macrophage CSF (GM
      CSF) detected by ELISA to 5.0 and 9.5 times, respectively, the amount released by
      the static controls at 24 hours, but it had no significant influence on the
      release of granulocyte CSF or macrophage CSF. The results of reverse
      transcriptase-polymerase chain reaction demonstrated that GM-CSF mRNA began to
      increase as early as 2 hours after initiation of 15 dyne/cm2 shear stress and
      continued to increase with time, reaching a peak of about four times the control
      levels at 24 hours. This increase in GM-CSF mRNA levels in response to shear
      stress depended on protein synthesis, because it was blocked by cycloheximide.
      Neither nuclear run-on assay or luciferase assay using a reporter gene containing
      GM-CSF gene promoter showed any significant change in transcription of the GM-CSF
      gene even after 24-hour exposure to a shear stress of 15 dyne/cm2. Actinomycin D
      chase experiments using a competitive polymerase chain reaction showed that shear
      stress extended the half-life of GM-CSF mRNA from approximately 23 to 42 minutes
      in HUVECs. These findings suggest that fluid shear stress increases the
      production of GM-CSF in HUVECs via mRNA stabilization.

PMID- 9562440
TI  - Cytosolic alkalinization of vascular endothelial cells produced by an abrupt
      reduction in fluid shear stress.
AB  - Reductions in fluid shear stress produce endothelium-dependent vasoconstriction
      and promote neointimal hyperplasia, but the intracellular signaling mechanisms
      involved in these processes are poorly understood. To examine whether decreases
      in fluid shear stress affect endothelial cytosolic pH, carboxy
      seminaphthorhodafluor-1-loaded rat aortic endothelial cells were cultured in
      glass microcapillary tubes and examined during abrupt reductions in laminar flow.
      After a 30-minute exposure to a shear stress of 2.7 dyne/cm2 in bicarbonate
      buffer, the acute reduction of fluid shear stress from 2.7 to 0.3 dyne/cm2
      transiently increased cytosolic pH from 7.20+/-0.02 to 7.47+/-0.07 (mean+/-SEM,
      P<.05 versus control). This was not affected by prior inhibition of the Na+-H+
      exchanger with 10 micromol/L ethylisopropylamiloride but was abolished in
      bicarbonate-free buffer. Recovery from an ammonium chloride prepulse-induced acid
      load occurred more rapidly when fluid shear stress was abruptly reduced from 2.7
      to 0.3 dyne/cm2 after maximal acidification (+0.04+/-0.02 pH unit at 2 minutes)
      than when shear stress was maintained at 2.7 dyne/cm2 continuously (0.00+/-0.00
      pH unit at 2 minutes, P<.05). This accelerated cytosolic pH recovery was
      dependent on the presence of bicarbonate ion and was blocked by the addition of
      the exchange inhibitors DIDS (100 micromol/L) and ethylisopropylamiloride or by
      removal of buffer Na+, indicating that the acute reduction in fluid shear stress
      activates the extracellular Na+-dependent Cl(-)-HCO3- exchanger and the Na+-H+
      exchanger and increases cytosolic pH in vascular endothelial cells.

PMID- 9562441
TI  - Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric
      oxide.
AB  - The purpose of this study was to determine whether superoxide anion is produced
      endogenously in the rat aortic adventitia and whether sufficient superoxide anion
      is produced to interfere with the response of the rat aorta to nitric oxide.
      Relaxation was measured in rings of the rat thoracic aorta, which were oriented
      so that the adventitial or luminal surface could be preferentially exposed to
      nitric oxide or sodium nitroprusside. To accomplish this, the rings were mounted
      (1) with the adventitia facing outward, (2) with the adventitia facing inward
      after inverting, or (3) with the adventitia facing outward after inverting twice
      (to control for the inverting procedure). The relaxation to nitric oxide, but not
      to sodium nitroprusside, was less in rings with the adventitia facing outward
      compared with those in which it faced inward. In contrast, the response to nitric
      oxide via either surface was similar when extracellular superoxide anion was
      scavenged with superoxide dismutase. Incubation of rings with nitro blue
      tetrazolium (NBT) resulted in blue formazan staining of the adventitia, and
      lucigenin chemiluminescence was significantly greater when detected from the
      adventitial compared with the intimal aspect of the artery. The reduction of NBT
      in intact aortic rings was 30+/-2 pmol x min(-1) x mg(-1) and was significantly
      decreased by superoxide dismutase to 19+/-2 pmol x min(-1) x mg(-1) and by a
      synthetic superoxide dismutase mimic, Euk-8, to 11+/-2 pmol x min(-1) x mg(-1).
      The NADPH oxidase inhibitor, diphenyleneiodonium, decreased NBT reduction to 9+/
      1 pmol x min(-1) x mg(-1), whereas inhibitors of xanthine oxidase, mitochondrial
      oxidases, and nitric oxide synthase were ineffective. Immunohistochemical
      staining indicated the localization of NADPH oxidase proteins gp91phox, p22phox,
      p47phox, and p67phox almost exclusively in the adventitia of the rat aorta with
      no substantial staining in the media. These results indicate that NADPH oxidase
      located in the adventitia of rat thoracic aorta generates sufficient
      extracellular superoxide anion to constitute a barrier capable of inactivating
      nitric oxide. This study suggests that adventitial superoxide anion can play a
      role in the pathophysiology of the arterial wall.

PMID- 9562442
TI  - Protective role of pulmonary nitric oxide in the acute phase of endotoxemia in
      rats.
AB  - We present for the first time direct continuous assay of NO concentration
      (porphyrinic sensor) in the lung parenchyma of Sprague-Dawley rats in vivo during
      endotoxemia. Intravenous infusion of lipopolysaccharide (LPS, 2 mg x kg(-1) x
      min(-1) for 10 minutes) stimulated an acute burst of NO from constitutive NO
      synthase (NOS) that peaked 10 to 15 minutes after the start of LPS infusion,
      mirroring a coincident peak drop in arterial pressure. NO concentration declined
      over the next hour to twice above pre-LPS infusion NO levels, where it remained
      until the rats died, 5 to 6 hours after LPS infusion. The chronic drop in
      arterial pressure observed from 70 minutes to 6 hours after the start of LPS
      infusion was not convincingly mirrored by a chronic increase in NO concentration,
      even though indirect NO assay (Griess method, assaying NO decay products NO2-/NO3
      ) showed that NO production was increasing as a result of continuous NO release
      by inducible NOS. A NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg
      i.v.) injected 45 minutes before LPS infusion, resulted in sudden death
      accompanied by macroscopically/microscopically diagnosed symptoms similar to
      acute respiratory distress syndrome <25 minutes after the start of LPS infusion.
      Pharmacological analysis of this L-NNA+LPS model by replacing L-NNA with 1-amino
      2-hydroxy-guanidine (selective inhibitor of inducible NOS) or by pretreatment
      with S-nitroso-N-acetyl-penicillamine (NO donor), camonagrel (thromboxane
      synthase inhibitor), or WEB2170 (platelet-activating factor receptor antagonist)
      indicated that in the early acute phase of endotoxemia, LPS stimulated the
      production of cytoprotective NO, cytotoxic thromboxane A2, and platelet
      activating factor.

PMID- 9562443
TI  - Microtubules in cardiac hypertrophy: a mechanical role in decompensation?

PMID- 9562444
TI  - The working group report on science-based categories for abstracts: submitted to
      the annual scientific sessions. American Heart Association.

PMID- 9562445
TI  - Should elderly men be screened for prostate carcinoma?

PMID- 9562446
TI  - A genetic perspective of male germ cell tumors.
AB  - Adult human male germ cell tumors (GCTs) arise by transformation of germ cells
      (GCs). The transformed GCs exhibit pluripotentiality to differentiate into
      embryonic, extra-embryonic, and somatic tissue types, and are highly sensitive to
      cisplatin-based chemotherapy. Recent investigations into the genetics of GCTs
      have advanced methods of diagnosis and provided leads to the understanding of
      molecular basis of transformation, differentiation, and sensitivity/resistance.
      Cytogenetic and molecular cytogenetic studies have identified multiplication of
      12p, manifested in i(12p) or tandem duplication of 12p, as a unique change in
      GCTs which serves as a diagnostic marker. Ectopic over-expression of cyclin D2, a
      gene mapped to 12p, as early as in carcinoma in situ identifies a candidate gene
      in GC transformation. Genetic alterations identified in the tumor suppressor
      genes deleted in colorectal cancer, retinoblastoma 1 and non-metastatic protein
      23 (NME) in GCT suggest that their inactivation play a key role in transformation
      or differentiation. A number of regions of chromosomal deletion have been
      identified including those previously known to be deleted in various tumor types
      and novel candidate tumor suppressor gene sites such as 12q13, 12q22, and 5p15.1
      15.2. Identification and characterization of the genes in these sites will
      provide important clues in understanding the biology of GCT. The molecular
      studies have also enumerated several possible differentiation controls such as
      switching of KIT and mast cell growth factor gene expression in a lineage
      associated manner, and loss of certain types of genes such as NME in teratomas
      that may act in a dominant negative fashion in differentiation. The exquisite
      sensitivity of these tumors to chemotherapy is reflected in their over-expression
      of wild-type p53 protein and lack of TP53 mutations. These data indicate that
      multiple genetic events play a role in distinct pathways in the development of
      GCT, and further elucidation of the underlying genetic and biochemical mechanisms
      is central to unraveling biology and improving treatment of GCT.

PMID- 9562447
TI  - Clinical stage I nonseminoma: surgery versus surveillance.
AB  - The presentation of nonseminomatous germ cell tumor confined clinically to the
      testicle (clinical stage I) is associated with a 30% incidence of occult
      retroperitoneal metastases. For decades, the standard of care in these patients
      has been a retroperitoneal lymph node dissection (RPLND), both for staging
      purposes, and, in the pre-modern chemotherapy era, it was performed with curative
      intent. The improvements in combination chemotherapy during the past 20 years
      have resulted in the cure of most individuals with small volume recurrent
      disease, calling into question the continued need for RPLND. The strategy of
      surveillance and chemotherapy for the 30% who relapse has gained acceptance, and,
      with meticulous follow-up, can result in the same excellent cure rates seen in
      patients treated with the surgical option. Although primary chemotherapy has also
      been suggested as a treatment option, the majority of patients will receive that
      chemotherapy unnecessarily, and cure rates with this strategy will not surpass
      those for surveillance or RPLND. Prognostic factors have been developed that can
      successfully identify a group of patients who are at an extremely low risk of
      relapse, thus potentially sparing these individuals any additional therapy.
      However, attempts to define a very high risk population have been unsuccessful to
      date, and we await the development of newer biologic markers able to predict
      which patients are most likely to have occult retroperitoneal disease and
      therefore most likely to benefit from additional "adjuvant" therapy post
      orchiectomy.

PMID- 9562448
TI  - Primary chemotherapy after orchidectomy for stage I and II nonseminoma.
AB  - The effectiveness of combination chemotherapy in advanced germ cell cancer has
      led to re-evaluation of treatment approaches in early disease. For patients with
      stage I nonseminoma it became possible to contemplate an observation policy,
      relying on chemotherapy to rescue those who relapsed. Subsequently it has been
      shown that two cycels of adjuvant chemotherapy can prevent relapse in those at
      high risk. For patients with stage II nonseminoma, a policy of primary
      chemotherapy postorchidectomy leads to high cure rates, with avoidance of
      retroperitoneal lymph node dissection, and only a minority of patients requiring
      lymphadenectomy. The excellent prognosis of these patients increases the
      importance of minimising risks of any long-term treatment toxicity.

PMID- 9562449
TI  - Early stage and advanced seminoma: role of radiation therapy, surgery, and
      chemotherapy.
AB  - Testicular seminoma is an uncommon tumor that accounts for approximately 50% of
      all germ cell testicular tumors. The vast majority of patients present with early
      stage disease and almost all patients are cured of their disease. Management is
      based on disease extent with patients with stage I seminoma having numerous
      treatment options, varying from surveillance to adjuvant retroperitoneal
      radiation therapy and prophylactic adjuvant single-agent chemotherapy. Only 20%
      of patients present with more advanced disease; the majority of those have stage
      II disease with retroperitoneal lymph node involvement. The standard management
      is retroperitoneal radiation therapy with chemotherapy being used for patients
      with bulky disease. Systemic chemotherapy with cisplatin alone or etoposide and
      cisplatin is the standard approach to advanced and metastatic disease with cure
      rates approaching 85% to 90%. The goal of treatment is a cure with a minimum of
      complications. The current controversies include the optimum management of
      residual retroperitoneal mass (post-radiation therapy or chemotherapy), the
      management of patients with second testicular or bilateral testicular tumors, the
      management of testicular intraepithelial neoplasia, and the management of
      seminoma in immunosuppressed patients.

PMID- 9562450
TI  - Prognostic factors in metastatic germ cell tumors.
AB  - Metastatic germ cell cancer is a very heterogeneous group with respect to
      prognosis under cisplatinum-based chemotherapy. The main determinants of complete
      response and survival are not only the extension of the metastases but much more
      the biology of the underlying tumor which is represented by the location of the
      metastases (pulmonary versus nonpulmonary visceral metastases (liver, bone,
      central nervous system) and the level of the marker elevation (AFG, HCG, LDH).
      Using these parameters patients with seminoma can be in two or three prognostic
      divided groups, depending on the model used; nonseminomatous germ cell cancer can
      be divided in three prognostic groups (good, intermediate and poor prognosis)
      with a 5 year survival of 90%, 70%, and 50%, respectively. The rate of marker
      decline and AFP- "surge" are not proven to be significant indicators of prognosis
      after the start of chemotherapy. Also, molecular markers i12p, p53, Rb, DNA
      repair-capacity, etc, currently do not contribute to the prognostic models. In
      conclusion, with the present available prognostic models the patients with
      seminomatous as well as nonseminomatous cancer can be attributed to different
      prognostic groups for first-line as well as salvage treatment. This allows to the
      selection of patients for a risk adapted treatment and for the investigation of
      less toxic regimen for good prognosis patients and more aggressive protocols for
      intermediate and in particular poor risk patients.

PMID- 9562451
TI  - Therapy for good risk germ cell tumors.
AB  - Patients with good-prognosis germ cell tumors are those with the highest
      likelihood of cure. By identifying pre-treatment risk assignment, these patients
      may be treated with the most efficacious and least toxic regimens, while poor
      risk patients may be selected to receive potentially more toxic combinations to
      optimize cure rates. The lack of uniform criteria of good-risk disease has been
      addressed by an international consortium, the International Germ Cell Cancer
      Collaborative Group. Recommendations for three risk strata, defined by serum
      tumor markers and specific sites of disease provide reproducible subsets of good
      , intermediate-, and poor-risk populations that allow international trial
      collaborations and direct comparison of good-risk therapies and outcomes. Despite
      different criteria defining good-risk disease, trials in these patients have
      successfully eliminated bleomycin from combination regimens, have reduced the
      number of cycles of therapy, and have proven that carboplatin cannot replace
      cisplatin. As a consequence of controlled studies, three cycles of bleomycin,
      etoposide, and cisplatin (BEP) or four cycles of etoposide and cisplatin, using a
      5-day etoposide schedule have been established as American standards. In Europe,
      four cycles of BEP using the 3-day etoposide schedule is considered the standard
      schedule. Because the schedule of etoposide is not uniform, prospective
      evaluation is necessary to determine whether the 3-day European standard is the
      equivalent of the 5-day American standard.

PMID- 9562452
TI  - Poor prognosis germ cell tumors: current status and future directions.

PMID- 9562453
TI  - Role of surgery in management of germ cell tumor.

PMID- 9562454
TI  - Primary salvage treatment of recurrent germ cell tumors: experience at Indiana
      University.

PMID- 9562455
TI  - Germ cell tumors: dose-intensive therapy.
AB  - Dose intensive chemotherapy in germ cell tumor patients has become a relatively
      safe procedure after the introduction of growth factors and the availability of
      autologous stem cells for hematopoietic rescue. Carboplatin and etoposide are the
      most active drugs available today, and are given in one or two subsequent cycles
      at dosages between 1000 and 2000 mg/m2 and 1200 and 2400 mg/m2, respectively. The
      potency of this approach is shown by the induction of long-term disease-free
      survival in a small proportion of patients with multiply relapsed or far advanced
      disease, deemed incurable with conventional chemotherapy. This observation
      indicates that cisplatin refractoriness can be overcome by high-dose carboplatin
      and etoposide. High-dose treatment (HDT) instituted earlier in the course of the
      disease, ie, for first-line salvage or even in first-line treatment of poor risk
      patients is better tolerated and is hoped to lead to superior tumor eradication.
      The value of HDT needs to be determined in randomized studies, some of which are
      under way.

PMID- 9562456
TI  - Gonadal function in men with testicular cancer.
AB  - This article reviews current knowledge on the effect of testicular germ cell
      cancer (TGCC) on gonadal function and of the cancer treatment on spermatogenesis
      and Leydig cell function. It seems likely that development of TGCC shares common
      etiological factors with development other types of testicular dysfunction. This
      suggestion is supported by the observation that men with various types of gonadal
      dysfunction such as testicular dysgenesis, androgen insensitivity syndrome, and
      cryptorchidism have increased risk of testicular cancer. Epidemiological and
      clinical data indicate common etiology between testicular germ cell cancer and
      other abnormalities in male reproductive health such as infertility and
      cryptorchidism. These observations are in agreement with the suggestions of
      hormonal involvement in the etiology of testicular cancer. It is well documented
      that testicular cancer is associated with impaired spermatogenic function and
      some patients have impairment of Leydig's cell function already before
      orchidectomy. The degree of spermatogenic dysfunction is higher than what can be
      explained by local tumor effect and by a general cancer effect. These
      observations are supported by histological investigations, which have shown a
      high prevalence of abnormalities of spermatogenesis in the contralateral testis
      in patients with unilateral TGCC. The spermatogenetic function is still severely
      impaired after orchidectomy and radiotherapy as well as chemotherapy induce
      further dose-dependent impairment of spermatogenesis. Recovery of spermatogenesis
      after treatment may be long, in some patients lasting more than 5 years.
      Sufficient androgen production is seen in the majority of the patients but some
      patients do suffer from testosterone deficiency. The effect of chemotherapy on
      Leydig's cell function seems to be dose dependent. Trials on protection of
      spermatogenetic function against the harmful effects of radiotherapy and
      chemotherapy by suppression of spermatogenesis has not been successful. The only
      way to maintain fertility is to limit gonadal exposure to harmful agents.
      Moreover cryopreservation of semen should be done before treatment. The optimal
      time for cryopreservation is before orchiectomy at least in some patients.
      Generally men with TGCC need counselling about their reproductive function, with
      respect to semen cryopreservation, chance for recovery of spermatogenesis,
      fertility, and the possibility of need for androgen replacement.

PMID- 9562457
TI  - Management of malignant germ cell tumors of the ovary.
AB  - Malignant germ cell tumors of the ovary are rare gynecologic tumors usually
      affecting young women. These tumors are commonly divided into two main groups:
      dysgerminomas and nondysgerminomas, although frequently many may contain mixed
      pathology. In contrast to epithelial ovarian cancers, ovarian germ cell tumors
      (OGCT) commonly present at an early stage and may frequently be confined to one
      ovary. They commonly respond well to initial chemotherapy and many patients may
      be salvaged with second-line therapy. Moreover, dysgerminomas are exquisitely
      radiosensitive. OGCT frequently produce tumor markers detected in the serum that
      may be helpful in the initial management and follow-up of these patients. The
      current management of women with OGCT emphasizes initial conservative surgery (in
      women desiring future fertility) with comprehensive surgical staging and surgical
      cytoreduction of advanced disease, followed by prompt institution of combination
      intravenous chemotherapy as adjuvant or primary therapy in the majority of cases.
      The combination of surgical resection and systemic chemotherapy cures the
      majority of women affected with OGCT and many may retain normal reproductive
      function after the completion of therapy.

PMID- 9562458
TI  - Central nervous system germ cell tumors.

PMID- 9562459
TI  - Presenilin 1 cleavage is a universal event in human organs.
AB  - A panel of antibodies raised against various regions of human presenilin 1(PS1)-
      the amino-terminal domain, the domain between the transmembrane domains 1 and 2,
      the cleavage-site, loop domains, or carboxyl-terminal domain--was prepared to
      analyze PS1 in human tissues. We observed the predominance of two fragments (28
      kDa NH2 and 18-kDa COOH fragments) in various tissues, including cerebral
      cortices. In addition to these two fragments, we found a previously unidentified
      amino-terminal fragment of PS1 with Mr 14 kDa in the lungs, spleen, pancreas, and
      testes. Using a sensitive ELISA for PS1, we measured the amount of PS1 species in
      tissues and found high contents of PS1 fragment in the testes. Our data show that
      common and unique processing pathways of PS1 occur in a tissue-dependent manner.
      It is likely that cleavage at the loop structure of PS1 to produce a functional
      form is a common event in human organs.

PMID- 9562460
TI  - Abeta42, presenilins, and Alzheimer's disease.
AB  - The significance of amyloid beta protein, especially those ending at the 42nd
      residue (Abeta42), in the pathogenesis of familial Alzheimer's disease (FAD)
      linked to the mutations of presenilins, was examined by transfection studies
      using cultured cells and immunohistochemical analysis of autopsied brains. The
      levels of Abeta42 secreted from cells transfected with mutant presenilins linked
      to FAD, as well as the Abeta42 burden in the cortices of patients with presenilin
      mutation were elevated. Thus, mutations in presenilin genes may enhance the
      production and deposition of Abeta42 in the brains, thereby leading to
      Alzheimer's disease.

PMID- 9562461
TI  - Metabolism of presenilin 1: influence of presenilin 1 on amyloid precursor
      protein processing.
AB  - To create model systems to examine presenilin 1 (PS1) metabolism in vivo, we
      generated transgenic mice expressing wild-type and A246E mutant human PS1. Our
      data indicate that both wild-type and mutant PS1 is endoproteolytically cleaved
      into 27 kDa N- and 17 kDa C-terminal fragments, which are the principal PS1
      species found in normal mammalian brain. To examine the influence of mutant PS1
      on Abeta formation and deposition in brain, we mated mice expressing wild-type
      and mutant PS1 to mice expressing a murine amyloid precursor protein (APP) with a
      humanized Abeta domain and missense mutations linked to a Swedish familial
      Alzheimer's disease kindred (APP.swe). In the brains of mice that co-express
      mutant PS1 and APP.swe, the ratio of Abeta1-42/43 to 1-40 was elevated by 50%
      compared to mice expressing APP.swe alone or mice expressing APP.swe and wild
      type PS1. These data suggest that mutations in PS1 may cause early onset
      Alzheimer's disease by enhancing the concentration of longer, and more
      amyloidogenic, 42 and 43 residue Abeta peptides.

PMID- 9562462
TI  - Presenilin 1 is actively degraded by the 26S proteasome.
AB  - The metabolic pathways governing the turnover of presenilin 1 (PS1) have been
      incompletely worked out. The PS1 holoprotein has low abundance in many cells and
      appears to undergo endoproteolytic cleavage near residue 298. We provide evidence
      that one mechanism by which the PS1 holoprotein is degraded is through the action
      of the 26S proteasome. We also show that the proteasome does not participate in
      the endoproteolytic cleavage.

PMID- 9562463
TI  - Regulation of apoptosis by presenilin 1.
AB  - Familial Alzheimer's disease is transmitted as an autosomal dominant disorder
      and, in 5-10% of the cases, is caused by mutations in the coding regions of two
      homologous genes, Presenilin 1 and 2 (PS1 and PS2). Previously, we have shown
      that PS2, a homolog of PS1. regulates apoptosis induced in neurons by trophic
      withdrawal or Abeta, and in T-cells by Fas ligand. We now report that PS1 also
      regulates apoptosis. Both wild-type and the H115Y mutant form of PS1 enhance Fas
      mediated apoptosis in Jurkat cells. We also observed that wild-type and the H115Y
      mutant form of PS1 differentially regulate Jun Kinase, an important enzyme
      regulating apoptosis.

PMID- 9562464
TI  - Apoptosis decision cascades and neuronal degeneration in Alzheimer's disease.
AB  - An important and unique characteristic of neurons is that they are nondividing
      and irreplaceable. The decisions, then, to engage and execute the apoptotic
      program are most serious. One of the most surprising new findings in AD brain
      pathology to date is the large number of neurons affected by DNA damage, even
      early in the disease process. This may be due to the pressure of chronic
      apoptotic stressors and the induction of factors which protect the cells from
      terminal apoptosis. It is possible that Bcl-2, Ref-1, and other such factors may
      act as apoptotic check points. Thus, there may exist a dynamic and extended
      competitive decision-making process between cell death processes and compensatory
      responses in the AD brain, forming a type of neuronal apoptosis decision cascade.

PMID- 9562465
TI  - A new paradigm for neurotoxicity by FAD mutants of betaAPP: a signaling
      abnormality.
AB  - We have demonstrated that normal betaAPP695 behave as a signaling receptor and
      indicated that point mutations at V642 create autoactive betaAPP in signal
      transduction. Cellular expression of those familial Alzheimer's disease
      associated mutants causes neuronal cells to undergo apoptotic death; and
      procedures inhibiting the signal of normal betaAPP block the mutant-induced
      apoptosis. We have also shown that the mutant-induced death is mediated by
      intracellular G protein activity but not by secretion of Abeta peptides.
      Accordingly, the mutant-induced death requires a cytoplasmic domain but not the
      41st and 42nd residues of the Abeta region. These studies provide a novel insight
      that betaAPP may play a normal role as a death receptor and that Alzheimer's
      disease-relevant abnormality occurred in this function may lead neurons to
      suicidal degeneration.

PMID- 9562466
TI  - Complete genomic screen in late-onset familial Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex genetic disorder. Linkage analysis has
      helped unravel a portion of the genetic component of AD by identifying four loci
      that play a role in the genetics of AD (amyloid precursor protein, presenilin 1,
      presenilin 2, and apolipoprotein E). These loci account for approximately 50% of
      the genetic etiology of AD. A total genomic screen is an efficient way to
      identify additional genetic effects in AD. A series of multiplex late-onset (>60
      years) AD families were ascertained (NINDS-ADRDA diagnostic criteria) and
      sampled. A subset (n = 16) of the largest families (52 affecteds with DNA, 83
      unaffecteds with DNA) were used to rapidly screen the genome (n = 280 markers)
      for additional major genetic effects. Critical values for regional follow-up were
      p < or =0.05 for SimIBD or sibpair analysis and/or a LOD score > or = 1.00.
      Fifteen regions warranted initial follow-up based on these criteria. An
      additional screening set was used (n = 38 families, 89 affecteds with DNA, 216
      unaffecteds with DNA) for the follow-up analysis. These analyses revealed four
      regions of continued interest on chromosomes 4, 6, 12, and 20. Chromosome 12
      presented the strongest results. Peak two point "affecteds only" LOD scores were
      1.3, 1.6, 2.7, and 2.2 and (affected relative pair SimIBD) p values were 0.04,
      0.03, 0.14, and 0.04 for D12S373, D12S1057, D12S1042, and D12S390, respectively.
      These markers span approximately 30 cm near the centromeric region of chromosome
      12. Sibpair analysis resulted in two point Maximum Lod Score (MLS) results of
      0.4, 1.2, 3.2, and 1.0 for the above markers. Multipoint MLS analysis supported
      these findings. Saturation mapping of all available markers in the chromosome 12
      region as well as further investigation of the regions on 4, 6, and 20 is ongoing
      with candidate gene analysis to follow.

PMID- 9562467
TI  - Genetic risk factors in Japanese Alzheimer's disease patients: alpha1-ACT, VLDLR,
      and ApoE.
AB  - We studied the polymorphism of alpha1-antichymotrypsin (ACT), very low density
      lipoprotein receptor (VLDLR) and apolipoprotein E (ApoE) genes in 200 control
      subjects and 65 patients with Alzheimer's disease (AD) in Japanese. The subjects
      consisted of 30 patients with early onset familial Alzheimer's disease (FAD), a
      patient with late onset FAD, 29 patients with an early onset isolated form of AD,
      and 5 patients with late onset AD. ApoE genotypes were significantly different
      between controls and FAD (p < 0.0005) or AD (p < 0.05), and patients carrying at
      least one ApoE epsilon4 allele were found in 44% of FAD and 34.3% of AD; both
      were significantly different (p < 0.001) from the controls (12.5%). ACT genotypes
      and allele frequencies were not different among these groups except for genotypes
      between ApoE epsilon4 FAD and ApoE epsilon4 controls (p = 0.019). There was a
      slight but significant increase of the 5 repeat allele of VLDLR in AD (p =
      0.014), but the difference was rather diminished in the presence of an ApoE
      epsilon4 allele. None of combinations of ACT and VLDLR genotypes in the presence
      or absence of an ApoE epsilon4 allele gave significant difference. Thus, we
      conclude that among the reported genetic risk factors, ApoE epsilon4 is the only
      definite risk factor for both FAD and AD, and the VLDLR polymorphism might be
      associated with AD cases in Japanese.

PMID- 9562468
TI  - mtDNA polymorphisms in Japanese sporadic Alzheimer's disease.
AB  - We screened 92 Japanese patients with sporadic AD (clinically diagnosed: 72
      cases; autopsy-confirmed: 20 cases) and 59 age-matched controls for mitochondrial
      polymorphisms previously reported to be associated with increased risk in
      Caucasian AD. The polymorphisms in tRNA(Gln) (nt. 4336), 16S rRNA (nt. 3196), and
      ND1 (nt. 3397) were not found in either in Japanese AD or age-matched controls.
      The frequencies of these polymorphisms in Japanese seems to be very rare if not
      absent, indicating that these three mutations are not likely to be genetic risk
      factors of Japanese AD. In the analysis of polymorphisms of 12S rRNA, however, we
      identified two novel mutations, an insertion of three cytosines and an A to G
      transition at nt. 856, which have not been described before. The insertion of
      three cytosines was observed in one of the 90 AD cases, but not in 59 normal
      controls. The A to G transition at nt. 856 was found in 2 of the 90 AD cases, but
      not in 59 normal controls. These results raise the possibility that the mutations
      in the 12S rRNA are genetic risk factors for AD in Japanese population.

PMID- 9562469
TI  - Cis-acting human ApoE tissue expression element is associated with human pattern
      of intraneuronal ApoE in transgenic mice.
AB  - Apolipoprotein E polymorphic variants (ApoE-epsilon2, epsilon3, and epsilon4) are
      associated with the age of onset distribution and risk of Alzheimer disease. The
      question of whether ApoE is expressed at a comparatively low level in human
      neurons compared to astrocytes, or whether ApoE enters neuronal cytoplasm via
      altered endosomal metabolism is important to understanding potential pathogenic
      roles for ApoE as a susceptibility gene in Alzheimer disease. ApoE deficient
      ("knock-out") mice received large human genomic DNA fragment transgenes for each
      of the three common apoE alleles. All transgenic mice demonstrated
      glial/astrocytic (normal rodent pattern), as well as cortical intraneuronal ApoE
      immunoreactivity with all three human isoforms and at multiple ApoE human allele
      doses (Xu et al. (32)). To test whether ApoE intraneuronal immunoreactivity was
      due to ApoE gene sequences between mouse and human, we examined another set of
      mice constructed using targeted replacement so that the human ApoE gene was
      placed under mouse gene promoters. Current analyses show that targeted
      replacement recombinant mice show normal rodent glial expression pattern, but no
      ApoE neuronal immunoreactivity through six months of age compared to large human
      genomic DNA fragment transgenic mice, which show neuronal content of ApoE
      throughout adult life. We conclude that cis-acting DNA sequences, rather than the
      specific sequence of the ApoE gene, may be responsible for low levels of
      transcription activity in cortical neurons.

PMID- 9562470
TI  - Accumulation of amyloid beta protein in transgenic mice.
AB  - Carboxyl-terminal fragments of beta amyloid precursor protein (betaAPP) were
      expressed in mice under the transcriptional control of an ubiquitous promoter
      system, based upon a chicken beta-actin (betaA) promoter combined with
      cytomegalovirus (CMV) enhancer to obtain a systemic overproduction of amyloid
      beta protein (Abeta). Three transgene constructs were designed to encode signal
      peptide and carboxyl-terminal 99 amino acid residues to betaAPP (NOR-beta),
      methionine and C-terminal 103 amino acid residues of betaAPP (deltaNOR-beta), and
      methionine and C-terminal 103 amino acid residues with KM-NL substitution of
      betaAPP (deltaNL-beta). Although the transcriptional mRNA level and post
      translational protein level from transgenes showed the same expression pattern,
      both the expression of Abeta and distribution of Abeta deposits were completely
      different among these strains. In NOR-beta mice, considerable amounts of Abeta
      were detected in plasma and Abeta deposits were observed in the pancreas. Brain
      Abeta deposits and small amounts of plasma Abeta were recognized in deltaNL-beta.
      These findings indicate that tissue specific processing and transgene constructs
      are major factors to determine the distribution of Abeta deposits.

PMID- 9562471
TI  - GM1 ganglioside-bound amyloid beta-protein in Alzheimer's disease brain.
AB  - The central question related to beta-amyloidogenesis is how amyloid beta-protein
      (Abeta) is generated and deposited. To address this issue, we investigated the
      early stage of beta-amyloidogenesis using cerebral cortices from Alzheimer's
      disease and Down's syndrome patients and normal aged individuals with BC05, a
      specific monoclonal antibody for Abeta42(43), which is believed to be an
      initially deposited Abeta species, as a probe. In that study, we found that
      Abeta42 is bound to membranes in brains with abundant diffuse plaques, and that
      the bound lipid is likely GM1 ganglioside. To further characterize this novel
      Abeta species, we investigated its reactivity to cholera toxin, and performed
      immunoprecipitation experiments using several anti-Abeta monoclonal antibodies.
      The immunoprecipitates obtained with BAN052 (specific for the N-terminus of
      Abeta), but not BC05 and 4G8 (specific for Abeta17-24), showed significant Abeta
      immunoreactivity and cholera toxin reactivity. The present results strongly
      suggest that Abeta binds to a GM1 ganglioside in such a way that the bound Abeta
      is only recognized by BAN052, of the monoclonal antibodies used in this study.

PMID- 9562472
TI  - Alzheimer's disease as proteolytic disorders: anabolism and catabolism of beta
      amyloid.
AB  - Recent studies on the familial Alzheimer's disease (FAD)-linked mutations in
      three independent genes have established the pathogenic role of beta-amyloid
      (Abeta) deposition as a common pathway leading to neurodegeneration. Most of
      these mutations seem to contribute to Abeta deposition by directly causing the
      overproduction of Abeta1-42, a form of Abeta with high insolubility attributed to
      its carboxyl-terminal structure, through secretory proteolysis. In contrast, the
      mechanism of Abeta deposition in sporadic Alzheimer's disease (SAD), which
      accounts for more than 90% of disease cases, is unclear. Because Abeta
      overproduction is rarely observed in SAD, a possible candidate mechanism is a
      decreased degradation, or dyscatabolism, of Abeta. It is notable that a reduction
      in catabolism of only 30-50% is estimated to exert an equivalent effect on Abeta
      metabolism as the overproduction seen in FAD. Identification of the in vivo
      catabolic processes responsible for Abeta disposition would provide a new basis
      for the development of preventive and therapeutic measures against the disease. I
      hypothesized recently that aminopeptidase-catalyzed proteolysis of Abeta may
      limit the rate of Abeta catabolism and that the reduction of a certain
      aminopeptidase activity would lead to Abeta dyscatabolism and thus to deposition
      (Aminopeptidase Hypothesis), based on the structural properties of Abeta
      deposited in human brain. Experimental and clinical observations supporting this
      hypothesis are accumulating although further work is necessary to fully evaluate
      its relevance. If the assumption proves to be true, both the familial and
      sporadic forms of AD may be referred to as "proteolytic disorders" in anabolic
      and catabolic terms, respectively.

PMID- 9562473
TI  - Effects of specific protease inhibitors on amyloid beta-protein 42 secretion.
AB  - Amyloid beta-protein (Abeta) is classified into two subspecies defined by its C
      terminal length, designated Abeta40 and Abeta42. Although Abeta42 accounts for
      only approximately 10% of secreted Abeta, this particular species is the most
      dominant species in Abeta deposits in Alzheimer's disease (AD) and normal aged
      brains and appears to be the initially deposited species. Secretion levels of
      Abeta42 have been shown to increase in patients affected by any form of early
      onset familial AD. Thus, the suppression of Abeta42 production or secretion could
      be a therapeutic strategy for AD. In this study, we examined whether protease
      inhibition affects the Abeta42 secretion ratio (Abeta42: total Abeta). Using
      specific inhibitors, we determined that the inhibition of calpain but not
      proteasome induces an increased Abeta42 secretion in cultured cells. These data
      suggest that calpain differentially affects the gamma-secretases generating
      Abeta40 and Abeta42 and indicate the possibility of developing compounds that
      reduce Abeta42 production and secretion though this pathway.

PMID- 9562474
TI  - Microglia, scavenger receptors, and the pathogenesis of Alzheimer's disease.
AB  - The senile plaque is the pathological hallmark of Alzheimer's disease. Senile
      plaques are composed of beta amyloid fibrils, associated with activated
      microglia, astrocytes, and dystrophic neurons. We have recently identified class
      A scavenger receptors as the main receptors mediating the interaction of
      microglia with beta amyloid fibrils. Adhesion of microglia to beta amyloid
      fibrils leads to immobilization of these cells on the fibrils, and induces them
      to produce reactive oxygen species. We propose that interactions of microglial
      scavenger receptors with fibrillar beta amyloid may stimulate the microglia to
      secrete apolipoprotein E and complement proteins, which may further contribute to
      neurotoxicity and neuronal degeneration. Therefore, microglial scavenger
      receptors may be novel targets for therapeutic interventions in Alzheimer's
      disease.

PMID- 9562476
TI  - Possible role of tau protein kinases in pathogenesis of Alzheimer's disease.
AB  - Tau protein kinases (TPK) I and II were isolated as candidate enzymes responsible
      for the hyperphosphorylation observed in PHF-tau. Four phosphorylation sites of
      tau were identified for each kinase, accounting for most, but not all, of the
      major phosphorylation sites of PHF-tau. Immunostaining with anti-TPKI antibody
      indicated that this kinase is up-regulated in AD brain. Such up-regulation of
      TPKI and phosphorylatioin of tau were reproduced by treating cultured hippocampal
      cells with amyloid beta (Abeta) protein. In addition, we found that TPKI can
      phosphorylate and inactivate pyruvate dehydrogenase (PDH), which is expected to
      result in depletion of acetyl-CoA, a key substrate of acetyl choline synthesis.
      Indeed, when septum cells were treated with Abeta, the level of acetyl choline
      decreased dramatically.

PMID- 9562475
TI  - Glial tau pathology in neurodegenerative diseases: their nature and comparison
      with neuronal tangles.
AB  - Tau-positive inclusions that occur in glial cells are called glial fibrillary
      tangles or, more simply, glial tangles. These include tuft-shaped astrocytes,
      thorn-shaped astrocytes, coiled bodies, and argyrophilic threads. The latter two
      structures occur in oligodendroglia. The tau protein in glial tangles is
      hyperphosphorylated and has similar immunohistochemical profiles to that in
      neurofibrillary tangles (NFTs) except that there are no epitopes derived from
      alternatively spliced exon 2 and 3. In contrast to NFTs, glial tangles rarely
      show solid filaments. Such NFT-associated molecules as ubiquitin, apolipoprotein
      E, alpha1-antichymotrypsin, and heparan sulfate are all absent from glial
      tangles. These characteristics suggest that glial tangles resemble the pre
      tangles that occur in neurons and are thought to represent an early stage of
      NFTs. Tau pathology in neurodegenerative diseases takes heterogenous forms.

PMID- 9562477
TI  - Analysis of message expression in single neurons of Alzheimer's disease brain.
AB  - Because many cell types and disease states exist in the sample of cells in even a
      very small region of Alzheimer's disease (AD) brain tissue, optimal understanding
      of disease mechanisms requires study at the level of the single cell. Our Golgi
      studies of single neurons in the AD brain have revealed reduced dendritic extent
      in many, but not all, brain regions. This reduced dendritic extent is interpreted
      as reduced capacity of neurons in AD to proliferate new dendritic material.
      Studies of message expression in single neurons reveal that neurons containing
      neurofibrillary tangles (NFTs) show reduced expression of messages for proteins
      related to growth of neuronal processes and to synapses. Neighboring neurons free
      of NFTs express these messages at levels approximating the levels expressed by
      single neurons from control brain. This reduction of expression of messages
      related to growth of neuronal processes and to synapses is selective, because
      expression of message for the lysosomal enzyme, cathepsin D, is increased in
      neurons containing NFTs. Simultaneous analysis of the expression of multiple
      genes by single neurons using an aRNA technique offers powerful capacity to
      profile message expression as a function of disease state of single cells.

PMID- 9562478
TI  - How to cope with Alzheimer's disease?
AB  - Alzheimer's disease (AD) is the most common causative brain disease of primary
      dementia in the elderly. The incidence of AD rises exponentially with age. Many
      countries, where the aging population is a national problem, have to face how to
      cope with AD. The main strategies against AD include the estimation of the exact
      size of the problem, the elucidation of etiology of AD, the development of
      effective treatment, and the establishment of the caring system for AD sufferers
      in the community. A recent fruit of the research is the new cholinomimetic agent
      E2020 (Donepezil), which is a highly selective acetylcholinesterase inhibitor. As
      a result of clinical trials, statistically significant improvements were seen in
      cognitive function of AD patients. However, E2020 is one of the neurotransmitter
      substitution therapies and is not specifically linked to the etiological
      treatment. We have to make efforts to establish a definitive therapy for AD and
      this depends on basic research, such as the molecular biology of AD. Many AD
      patients and their families expect fruitful result from this symposium, which
      will be a big milestone for the research of AD toward the 21st Century.

PMID- 9562479
TI  - The IFSO and obesity surgery throughout the world. International Federation for
      the Surgery of Obesity.

PMID- 9562480
TI  - Does gastric restriction surgery reduce the risks of metabolic diseases?
AB  - BACKGROUND: Certain risk factors for arteriosclerosis are associated with
      obesity, e.g. hypertension, insulin resistance, the high triglyceride - low HDL
      pattern. One aim in treating morbid obesity is to reduce these risk factors. This
      study was designed to follow metabolic risk factors after weight loss in 165
      morbidly obese patients who underwent a gastric restriction operation. METHODS
      AND PATIENTS: Lipid and hormone levels were analyzed before surgery and after 25,
      50, 75 and 100% loss of excess weight. Mean cholesterol and triglyceride levels
      were normal or slightly elevated. HDL cholesterol was also normal (41 mg/dl).
      Thirty eight percent of the patients had elevated cholesterol and triglyceride
      levels. Insulin levels were measured as an indicator of potential insulin
      resistance, and with a mean of 21 microU/ml it was at the upper normal level.
      RESULTS: After reaching 75% reduction of overweight in a mean time of 10 months,
      serum cholesterol levels were unchanged. Serum triglycerides, however, decreased
      by 35% (P<0.0001) and HDL cholesterol increased by 24% (P<0.0001). Insulin levels
      decreased to 8 microU/ml (P<0.0001). CONCLUSION: We found an amelioration in the
      metabolic parameters in 75% of the patients. Nevertheless morbidly obese patients
      were found to have fewer abnormalities in lipid and glucose metabolism than
      expected from data of overweight patients with metabolic syndrome. Further long
      term studies with careful evaluation of the metabolic parameters as risk factors
      in patients with morbid obesity need to be performed.

PMID- 9562481
TI  - Staple-line disruption following vertical banded gastroplasty.
AB  - BACKGROUND: The purpose of this study was to determine the frequency with which
      staple-line disruption occurs following vertical banded gastroplasty (VBG) in
      morbidly obese patients, to investigate the effect of this complication on weight
      loss, and to identify any clinical symptoms that might be associated with staple
      line disruption. METHODS: From April of 1992 to June of 1994, 60 patients with
      morbid obesity underwent VBG. Double-contrast radiographic examination of the
      upper gastrointestinal tract was performed on all patients at 6, 12, 24, and 36
      months postoperation to assess the integrity of the staple line. At these same
      times, the weight of each patient was measured, so that the patients found to
      have staple-line disruption could be compared to those without disruption in
      terms of weight loss. RESULTS: Over the duration of the study, staple-line
      disruption was found in 12 patients (20%). All of these patients demonstrated
      satisfactory weight loss. Between the group of patients with staple-line
      disruption versus the group without disruption, weight loss did not differ
      significantly at any time up to 3 years postoperation. In addition, in the
      patients with staple-line disruption, no clear symptomatology that might be
      associated with this complication was discovered. CONCLUSIONS: Our results lead
      to the conclusion that small disruptions in the staple line lack clinical
      importance and do not significantly affect weight loss for at least the first 3
      postoperative years. Furthermore, staple-line disruption does not seem to be
      associated with any specific clinical symptoms. Follow-up of all patients via
      barium meal is the correct approach for discovering the exact incidence of this
      complication.

PMID- 9562482
TI  - Revisional surgery after failed vertical banded gastroplasty: restoration of
      vertical banded gastroplasty or conversion to gastric bypass.
AB  - BACKGROUND: An increasing number of patients with a failed primary bariatric
      procedure present themselves for secondary treatment. Only a few studies have
      investigated critically the success of revisional surgery. In the present study,
      the effectiveness of revisional surgery for failed vertical banded gastroplasty
      (VBG) is analyzed: restoration of the VBG (reVBG) is compared to conversion to a
      Roux-en-Y gastric bypass (RYGB). PATIENTS AND METHODS: From 1980 to 1996, 136
      consecutive morbidly obese patients underwent primary RYGB (n = 20) or VBG (n =
      16). Weight loss, indications and complications after revisional surgery were
      registered. The rate of revisional surgery after primary and secondary bariatric
      procedures was estimated by means of a Kaplan-Meier analysis. RESULTS: Kaplan
      Meier analysis revealed that 56% of the patients will eventually require
      revisional surgery after initial VBG over a 12-year period compared to 12% after
      initial RYGB (P<0.01). After reVBG 68% will need revisional surgery over a 5-year
      period, while no further revisional surgery was required after conversion to a
      RYGB (P<0.05). Body mass index dropped significantly after reVBG or conversion to
      RYGB for insufficient weight loss (P<0.05), however, more revisional surgery was
      necessary after reVBG to achieve this result. The complication rate was
      comparable between reVBG and conversion to RYGB (33%). CONCLUSION: Conversion of
      a failed VBG to a RYGB is more effective than a reVBG, because conversion to RYGB
      provides satisfactory weight loss without requiring further revisional surgery.

PMID- 9562483
TI  - Vertical banded gastroplasty at more than 5 years.
AB  - BACKGROUND: Optimal evaluation of the results of surgery for morbid obesity
      requires a long-term follow-up for at least 5 years. METHODS: One hundred
      patients were operated by vertical banded gastroplasty (VBG) and revised with a
      follow-up of no less than 5 years. Sixty patients were morbidly obese with a body
      mass index (BMI) of between 40 and 50 kg/m2, and 40 were super-obese with a BMI
      of >50 kg/m2. Follow-up included 93 patients (93%). RESULTS: Initial surgical
      mortality was nil. Twenty-five patients required surgery for complications
      related to the technique (25%) and one patient died due to pulmonary embolism
      after a re-stapling operation. The percentage excess weight loss was 54.3%, and
      the BMI was 33 kg/m2 for the 84 patients followed to 5 years post VBG. Only 40
      out of 92 patients (43.5%), obtained the weight loss benefit due to the
      operation. None of them is able to eat a regular diet, and the quality of food
      intake has been severely affected in some of them. CONCLUSIONS: VBG is, in our
      experience, a safe and technically simple operation, but the long-term results
      are questionable. The reoperation rate was high, and weight loss and quality of
      life are superior with other operations.

PMID- 9562484
TI  - Roux-en-Y gastric bypass: an effective antireflux procedure in the less than
      morbidly obese.
AB  - BACKGROUND: Since Roux-en-Y gastric bypass (RYGBP) is an excellent antireflux
      procedure, why is it necessary to do it only for those who are morbidly obese:
      why not anyone who has had a longstanding severe weight problem with chronic
      disabling reflux esophagitis? METHODS: RYGBP was done primarily as an antireflux
      procedure in 332 patients late from 1987 through October 1996. Eighty-nine were
      less than 100 lb (45 kg) overweight. Forty-five were lost to follow-up. All but
      one had Visick ratings from 2 to 4 preoperatively. Thirty-one were primary RYGBP
      and 13 were conversions from previous gastroplasties. The diagnosis in each case
      was made by esophagogastroscopy with esophageal biopsy with or without the
      Bernstein test when indicated. RESULTS: Postoperatively, only one patient was
      symptomatic. The remaining had Visick ratings of 1. The average preoperative
      weight of 192 lb (87 kg) dropped to 145 lb (66 kg) postoperatively, or 67% of
      excess weight loss at a mean of 56 months. Compared to the morbidly obese group,
      there was no significant difference in 1-year postoperative laboratory values.
      CONCLUSION: This study supports the efficacy and safety of RYGBP for reflux
      esophagitis in the less than morbidly obese patient. Esophagitis is truly a
      comorbid condition of severe obesity, and it should be accepted as such. The
      arbitrary elimination from the consideration of candidacy for this procedure by
      those with a body mass index of less than 35 kg/m2 and unproven comorbidity
      appears unjustified.

PMID- 9562485
TI  - Laparoscopic adjustable esophagogastric banding: a preliminary experience.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding is an efficient surgical
      method in the treatment of morbid obesity. In order to reduce the number of
      complications, we have modified the technique to what we term 'laparoscopic
      adjustable esophagogastric banding'. METHODS: Between December 1994 and July
      1997, 126 laparoscopic adjustable banding procedures were carried out. Of these,
      40 underwent a gastric banding operation (group 1), and 86 underwent an
      esophagogastric banding procedure (group 2). RESULTS: The percentage loss of
      excess body weight curve was less rapid in group 2 compared to group 1 due to a
      different strategy in band filling. Follow-up to date shows that no problems with
      the pouch or the stoma have arisen in the esophagogastric banding group.
      CONCLUSIONS: Laparoscopic adjustable esophagogastric banding is a simpler and
      safer procedure than laparoscopic adjustable gastric banding. It also works as a
      very efficient anti-reflux procedure, at least in the short term. It appears to
      be equally efficient as a weight-reducing operation as gastric banding. Further
      follow-up of the patients involved is necessary in order to evaluate the results
      in the longer term.

PMID- 9562486
TI  - Assessment of the outcome of laparoscopic nonadjustable gastric banding and stoma
      adjustable gastric banding: surgeon's and patient's view.
AB  - BACKGROUND: The results of nonadjustable gastric banding (NAGB) and stoma
      adjustable gastric banding (SAGB) in the treatment of morbid obesity are
      compared. Of 300 patients operated laparoscopically with NAGB since 1993 and of
      25 with SAGB since 1994, 65 in the NAGB and 11 in the SAGB group were available
      for a 3-year follow-up study. METHODS: For assessment of the outcome of our
      laparoscopic approach in terms of weight loss, length of hospitalization,
      immediate and late postoperative wound complications, postoperative changes in
      the band and pouch area, were compared in patients from both groups. The
      patient's opinion on the outcome of the operation and the quality of
      postoperative digestion was recorded. RESULTS: There was no significant
      difference in the length of hospital stay and wound complication rate in the two
      groups or the weight loss at 36 months after surgery. There was a statistically
      significant lower incidence of postoperative food intolerance and vomiting and a
      lower rate of immediate and long-term reoperation rate in the SAGB group.
      CONCLUSION: SAGB is a method with less postoperative complications in food
      intolerance and vomiting in comparison with NAGB.

PMID- 9562487
TI  - Two years of practice in adjustable silicone gastric banding (LAP-BAND):
      evaluation of variations of body mass index, percentage ideal body weight and
      percentage excess body weight.
AB  - BACKGROUND: In the treatment of morbid obesity, surgery had been the only method
      of obtaining a good and enduring weight loss. Although the procedure of choice is
      still a matter of debate, among gastric restriction procedures LAP-BAND has
      become our first choice. METHODS: We report the results from 62 morbidly obese
      patients operated in the period October 1994-December 1996. Their characteristics
      were: mean age 35.6 years, mean body weight 130.6 kg, mean height 162.3 cm, mean
      body mass index (BMI) 49.9 kg/m2, mean percentage ideal body weight (%IBW) 215.7
      and mean excess weight (EW) 69.57 kg. RESULTS: Twenty-four months after surgery
      we found a mean BMI of 39.3, a mean %IBW of 168.6 and a mean % EW loss of 88.5.
      We removed the band in two patients: one after 9 months because of stoma stenosis
      and pouch enlargement in a woman who had been lost at follow-up, and the other
      for gastric slippage occurring after 18 months due to incorrect fixation of the
      band. CONCLUSION: Our results led us to consider LAP-BAND as the surgical
      approach for severe obesity among those patients selected for gastric
      restriction; indeed, it was very safe as well as effective and was rarely
      followed by complications.

PMID- 9562488
TI  - Distal gastric bypass/duodenal switch procedure, Roux-en-Y gastric bypass and
      biliopancreatic diversion in a community practice.
AB  - BACKGROUND: Hybrid procedures combining purely restrictive and purely
      malabsorptive components to achieve stable long-term weight reduction have
      evolved since the 1970s. In a solo surgical community-based practice over the
      period 1984-1997, three different hybrid procedures were utilized as primary
      operations in patients who had not had prior bariatric surgery. METHODS:
      Restrospective comparison of 32 patients who underwent biliopancreatic diversion
      (BPD), 138 patients who underwent distal gastric bypass Roux-en-Y (RGB) and 105
      patients undergoing distal gastric bypass/duodenal switch procedure (DS) with 2-4
      year follow-up in 37 DS patients. RESULTS: Height, initial weight and initial
      body mass index (BMI) were similar in the three groups. The DS patients were
      older. Mean BMI at 2 years fell from 49 to 29 kg/m2 in both DS and RGB. Mean
      percentage maximum preoperative weight lost was 40% in both the DS and RGB
      groups. Two-year mean percentage excess weight lost in DS was 78%, compared to
      74% in RGB. There were no operative deaths and no ulcers in the DS group.
      CONCLUSION: DS is an important new option for primary treatment of morbid
      obesity. It can be performed safely, with up to 4 year follow-up showing stable
      weight loss.

PMID- 9562489
TI  - Biliopancreatic diversion for treatment of morbid obesity: experience in 50
      cases.
AB  - BACKGROUND: Biliopancreatic diversion (BPD) by Scopinaro's method is an operation
      advocated by some surgeons as an effective treatment for morbid obesity. METHODS:
      Between February 1995 and April 1997 we performed BPD by Scopinaro's method on 50
      patients with morbid obesity (23 males), average age 41.4 years (range 20-63
      years), average body weight 135.08 kg (range 89-256 kg), mean body mass index
      (BMI) 50.65 kg/m2 (range 37.01-81.56 kg/m2). RESULTS: In all cases a gradual
      decrease in weight was obtained [mean BMI at 1 month: 44.8 kg/m2, at 6 months (31
      patients): 35.09 kg/m2, at 1 year (23 patients): 31.36 kg/m2, at 18 months (14
      patients): 29.89 kg/m2 and at 2 years (5 patients): 29.27 kg/m2]. At the same
      time a significant improvement in the pathological conditions associated with
      morbid obesity was observed. The patients were able to suspend oral
      antihypertensive and antidiabetic therapy as these parameters spontaneously
      returned to normal values by the sixth postoperative month; all cases showed a
      marked reduction in hypercholesterolemia and hypertriglyceridemia. Postoperative
      complications were: one death (2%) on the third day due to heart failure; two
      late intestinal occlusions (4%); one acute dilatation of the stomach (2%); one
      peritonitis caused by early dehiscence of the anastomosis (2%); five anastomotic
      ulcers (10%); two cases of protein malnutrition (4%). CONCLUSIONS: BPD by
      Scopinaro's method is a bariatric procedure which is technically complex. However
      is it safe and reproducible and it induces a substantial weight loss.

PMID- 9562490
TI  - Biliopancreatic diversion preserving the stomach and pylorus in the treatment of
      hypercholesterolemia and diabetes type II: results in the first 10 cases.
AB  - BACKGROUND: Besides weight loss Scopinaro's operation produces correction of
      hypercholesterolemia and noninsulin dependent diabetes mellitus in all patients
      who suffer from these conditions. These results encouraged us to perform
      biliopancreatic diversion (BPD) without gastric resection, thus preserving the
      functions of the stomach and pylorus in moderately overweight patients with
      hypercholesterolemia associated with diabetes type II and hypertriglyceridemia.
      METHODS: Between March 1996 and July 1997 we performed BPD without gastric
      resection on 10 moderately overweight patients [mean body mass index (BMI) = 33.2
      kg/m2]. All patients had suffered from hypercholesterolemia and
      hypertriglyceridemia for more than 5 years. Ten patients suffered from diabetes
      type 11; four of them had had insulin treatment or oral anti-diabetic agents; the
      other patients all had hyperglycaemia in the fasted state and diabetes confirmed
      by preoperative oral glucose tolerance test (OGTT). Five patients suffered from
      hypertension. RESULTS: In all patients, cholesterol and triglyceride levels
      returned to normal within the first postoperative month. Glycemia also stabilized
      at normal values in nine patients within the early weeks after surgery. One
      patient who took 70 U of insulin reduced his daily intake to 35 U 2 months
      postoperatively. In all patients blood pressure returned to normal. Weight loss
      was predictably slight (10-15 kg). CONCLUSIONS: Our experience with the procedure
      found that this new method seems to be as effective in controlling lipidic
      metabolism and diabetes II as the original version of BPD. As expected, weight
      loss is only moderate, so that the modified BPD is not suitable for very obese
      patients.

PMID- 9562492
TI  - What do patients, families and society expect from the bariatric surgeon?
AB  - The expectations of patients, their families and society of the bariatric surgeon
      are often unrealistic, but for different reasons. The morbidly obese patient
      often expects 'everything' from bariatric surgery. The patient's family is
      frequently ambivalent. Society, on the other hand, tends to unrealistically
      regard the morbidly obese as billboards advertising them as willful deviants
      whose problems can all be resolved by 'just pushing away from the table'. This
      invalid stereotype has prompted some to incorrectly regard bariatric surgery as
      an undeserved reward for individuals who will not control their own behavior. The
      undeserved intentional deviant status of the morbidly obese causes members of
      society to harass, mock or otherwise mistreat this subpopulation. Society's
      harmful, destructive and unjust weight harassment 'fat-ism' has made the morbidly
      obese modern day moral equivalents of lepers. We conclude that society must be
      persuaded to accept weight harassment as 'politically incorrect', subject to the
      same consequences as any other form of bigotry. Once society regards the morbidly
      obese as victims, not perpetrators, of their nonsurgically curable disease,
      bariatric surgery results should become held to similar standards as surgery for
      carcinoma, cardiovascular and other diseases. Until then, the morbidly obese
      remain the last true bastion of prejudice.

PMID- 9562493
TI  - The Cancun IFSO Statement on bariatric surgeon qualifications. International
      Federation for the Surgery of Obesity.

PMID- 9562494
TI  - Significance of the Cancun Statement.

PMID- 9562495
TI  - Wellness after obesity surgery.

PMID- 9562496
TI  - Aging in the human brain: a clarion call to stay the course.

PMID- 9562497
TI  - Phosphorylation of tau, Abeta-formation, and apoptosis after in vivo inhibition
      of PP-1 and PP-2A.
AB  - Chronic inhibition of protein phosphatases 1 and 2A in vivo was induced by
      infusion of okadaic acid into lateral ventricles of rat brain for up to 4 months.
      Cytoskeletal pathology, alterations of the amyloid precursor protein, and
      apoptotic cell death induced by this treatment followed a certain sequence and
      spatial distribution. Changes in the expression, phosphorylation, and subcellular
      distribution of neurofilament proteins and tau, as well as first signs of
      apoptotic cell death, occurred already after about 2 weeks. The distribution of
      apoptotic cells, however, was different from those revealing a high accumulation
      of hyperphosphorylated tau, indicating that those cytoskeletal pathology had no
      obvious sequelae for the viability of these neurones. A continuation of treatment
      for longer than 2 weeks induced diffuse deposits of both hyperphosphorylated tau
      and A beta-amyloid-immunoreactive material in white matter areas that increased
      in size and number over time. Because tau-phosphorylation is a regulator of the
      dynamic stability of microtubules, the pathology observed in the present
      experimental paradigm in the white matter might be viewed as an indication of a
      disturbed axonal transport. It is hypothesized that perturbations of the axonal
      transport might also be critically involved in the formation of paired helical
      filaments and amyloid deposits in Alzheimer's disease.

PMID- 9562498
TI  - Volumes of the entorhinal and perirhinal cortices in Alzheimer's disease.
AB  - We measured the volumes of the entorhinal, perirhinal, and temporopolar cortices
      on magnetic resonance images by using a recently designed histology-based
      protocol in 30 patients with early Alzheimer's disease (AD) and 32 healthy
      control subjects. Compared to the controls, all of these cortical regions were
      significantly atrophied in AD patients (p < 0.0001). However, the entorhinal
      cortex was the most severely involved brain region studied, with 40% volume loss,
      and this region provided the highest discriminative accuracy (92%) in separating
      patients with AD from healthy control subjects. Importantly, the entorhinal
      volume loss was evident already in mild AD. In addition, the volume of the
      entorhinal cortex was not dependent on age, but it did correlate significantly
      with the severity of the disease. Because it assesses the major site of initial
      neuropathological changes in AD, magnetic resonance imaging volumetric
      measurement of the entorhinal cortex can offer a tool for distinguishing AD
      patients even in the very early stages of the disease from healthy aged subjects.

PMID- 9562499
TI  - MRI of the hippocampus in Alzheimer's disease: sensitivity, specificity, and
      analysis of the incorrectly classified subjects.
AB  - In this study, magnetic resonance imaging (MRI) of the hippocampus for the
      diagnosis of early Alzheimer's disease (AD) is evaluated. We measured hippocampal
      volumes and the area of the medial hippocampus with a 1.5 T MR imager in 160
      subjects: 55 patients with probable AD according to the NINCDS-ADRDA criteria, 43
      subjects fulfilling the NIMH criteria of age-associated memory impairment (AAMI),
      42 cognitively normal elderly controls, and 20 controls younger than 50 years.
      Three methods for normalization were compared. The hippocampi were atrophied in
      the AD patients, but not in the AAMI subjects or the elderly controls. There was
      no significant correlation between hippocampal volumes and age in the nondemented
      subjects. The discrimination based on volumetry resulted in an overall correct
      classification of 92% of AD patients vs. nondemented elderly subjects, whereas
      discrimination based on hippocampal area was less accurate, producing a correct
      classification in 80% of the subjects. We conclude that the hippocampus as
      assessed by MRI volumetry is atrophied early in AD, and spared by aging or AAMI.
      A brief critical review of previous studies is in concordance with the presented
      data: all the previous studies that have used volumetry, have similarly ended up
      with a good classification, whereas simpler or subjective measurements, subject
      to various sources of bias, have produced most variable results.

PMID- 9562501
TI  - A model for structure-dependent binding of Congo red to Alzheimer beta-amyloid
      fibrils.
AB  - The cytotoxic A beta fibril is a logical candidate for the entity causing the
      initiating damage to neurons in Alzheimer's disease and Down's syndrome. We have
      derived a model of binding for the dye molecule, Congo red (CR), to a beta-sheet
      structure of beta-amyloid (1-42). This model is based on the crystal coordinates
      of CR binding to porcine insulin fibrils from Turnell and Finch. Intact insulin
      is composed of protein dimers and X-ray diffraction studies show that CR
      intercalates between two insulin monomers at an interface formed by a pair of
      antiparallel beta-strands. The intercalation of CR has disrupted the four main
      chain hydrogen bonds between the two beta-strands, but they are still tethered
      with each other through new hydrogen bonds with the CR nitrogen atoms. The CR
      molecule has been aligned along the homologous stretch of amino acids in
      Alzheimer beta peptide (two molecules in antiparallel distorted or pseudo beta
      sheet conformation) using the crystal coordinates from the Turnell-Finch paper to
      arrive at a putative structure for CR binding to Alzheimer's amyloid fibrils.

PMID- 9562500
TI  - Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain
      in Alzheimer's disease.
AB  - Recent studies have implicated increased oxidative stress in the pathogenesis of
      Alzheimer's disease (AD). Increased lipid peroxidation and decreased
      polyunsaturated fatty acid levels have been described in the brain in AD. Four
      hydroxynonenal (HNE), an aldehyde product of lipid peroxidation, has been
      demonstrated to be a neurotoxin in tissue culture and in vivo studies and is
      elevated in ventricular fluid in AD. We report here an increase in mean free HNE
      in multiple brain regions in AD compared with age-matched control subjects. These
      increases reached statistical significance in the amygdala and hippocampus and
      parahippocampal gyrus, regions showing the most pronounced histopathological
      alterations in AD. This study, in conjunction with cell culture studies, suggests
      that HNE may be an important substance in the pathogenesis of neuron degeneration
      in AD.

PMID- 9562502
TI  - Tubulin immunopositive structures resembling intracellular neurofibrillary
      tangles.
AB  - Tau protein promotes microtubule assembly. When aberrantly phosphorylated, it
      forms the core of neurofibrillary tangles (NFTs). We investigated by
      immunohistochemistry whether microtubules might also be involved in NFT
      formation. We found beta-tubulin immunoreactive NFT-like structures in Alzheimer
      disease, and, more frequently, in the parkinsonism dementia complex of Guam
      (bodig disease) and Down Syndrome. The beta-tubulin immunoreactive structures
      were intracellular and appeared at an early stage of tangle development. This may
      indicate an involvement of tubulin in NFT formation.

PMID- 9562503
TI  - Microglial expression of MHC class II increases in normal aging of nonhuman
      primates.
AB  - The search for factors that influence age-related behavioral and cognitive
      slowing is ongoing. Because microglia are involved in many neurological
      disorders, they may also contribute to changes in normal aging. To assess
      increases in microglial activity, we used an antibody against MHC class II to
      label microglia in three groups of brains from female Macaca nemestrina: juvenile
      (2-5 years), young adult (5-11 years), and mature (11-19 years). Image analysis
      was completed on four white matter and three gray matter regions in a single
      coronal plane. Microglial expression of MHC class II increased with age, and was
      highest in the white matter regions of the mature, or middle-aged, monkeys. The
      higher expression of this antigen may indicate that the cells will more easily
      respond to stimulation. Their location in the white matter suggest that they may
      influence myelin loss and the eventual cognitive decline in aged human and
      nonhuman primates.

PMID- 9562504
TI  - Regional cerebral blood flow and cerebrovascular risk factors in the elderly
      population.
AB  - Regional cerebral blood flow (rCBF) was studied in 60 elderly persons (aged 65 to
      84 years) recruited from a population-based study, with single photon emission
      computed tomography using technetium 99m-labeled hexamethylpropylene amine oxime.
      We investigated whether it is only age that affects rCBF or whether other factors
      can be indentified that explain this relationship. Using multiple linear
      regression analysis, increasing age was significantly associated with rCBF
      decrease in parietal, temporo-parietal, and temporal cortex, but not in frontal
      cortex. Adjustment with several risk factors for cerebrovascular disease,
      including hypertension, history of myocardial infarction, factor VIIc, factor
      VIIIc, cholesterol and HDL cholesterol, smoking, and diabetes mellitus had no
      influence on these relations. Conversely, the association between age and rCBF
      was no longer statistically significant after adjustment with fibrinogen and
      indicators of carotid atherosclerosis, including intima-media wall thickness of
      the carotid artery and plaques in the carotid artery. Correction with local
      ratings of cortical atrophy did not affect the relations between age and rCBF.
      The results suggest that in the elderly population rCBF declines with age in
      posterior cortical areas and that these changes may well be explained by the
      presence of atherosclerosis. Reduced contractility of the vascular muscle wall
      with increasing age resulting from atherosclerosis may be the underlying
      mechanism.

PMID- 9562505
TI  - Cerebral T2-weighted signal decrease during aging in the mouse lemur primate
      reflects iron accumulation.
AB  - 4.7 Tesla T2-weighted magnetic resonance images showed a highly significant
      signal decrease in the pallidum, substantia nigra, putamen, and a less
      significant decrease in the thalamus and the caudate of aging mouse lemurs
      (Microcebus murinus). We evaluated the contribution of iron deposits to the
      signal decrease comparing Perls' stained histological sections of six mouse
      lemurs brains aged 1 to 10 years to magnetic resonance images. In young animals,
      none of the brain structures was stained. A large number of iron deposits were
      visible in the pallidum and substantia nigra of aged animals and a moderate
      number in the middle aged ones. In the putamen, few iron deposits were visible in
      aged and middle-aged animals. The thalamus and the caudate appeared unstained
      with Perls' technique; iron was too low to be detected. The intensification of
      the reaction by diaminobenzidine revealed iron deposits in the thalamus of aging
      animals. This study suggests that in mouse lemurs, iron deposits are responsible
      for T2-weighted signal decrease in the central gray nuclei.

PMID- 9562506
TI  - Senescence-accelerated overexpression of S100beta in brain of SAMP6 mice.
AB  - S100beta is an astrocyte-derived protein with paracrine and autocrine effects on
      neurons and glia. Brain S100beta expression increases progressively with age, and
      this increased expression has been implicated as a factor underlying the
      increasing risk of Alzheimer's disease that accompanies aging. Senescence
      acceleration-prone (SAMP) mice are a group of inbred strains that provide animal
      models of aging and of various age-related disease processes in the brain and
      peripheral tissues. One of these strains, the osteopenic SAMP6, has not been
      previously associated with central nervous system alterations. We used Northern
      and Western immunoblot analysis and immunohistochemical labeling to examine
      S100beta expression in brains of SAMP6 mice. Cerebral tissue levels of S100beta
      and of S100beta mRNA were 2.2-fold and 1.6-fold those of senescence-resistant
      (control) mice at 4 months of age (p < 0.05 in each case), and were 3.7-fold and
      1.9-fold those of control mice at 6 months of age (p < 0.01 in each case). In
      contrast, levels of glial fibrillary acidic protein (GFAP) in cerebral
      hemispheres were not different from those of controls. Image analysis of
      immunohistochemical preparations showed increased numbers and immunoreactive
      intensity of S100beta-immunoreactive astrocytes in both the hippocampus and
      cerebral cortex of SAMP6 mice at 4 months of age (p < 0.05 or better in each
      case). These increases were greater in the hippocampus than in the cerebral
      cortex. In contrast, increases in numbers of GFAP immunoreactive astrocytes were
      noted only in the hippocampus. Our finding of increased S100beta gene expression
      in brains of SAMP6 mice mirror age-associated increases in S100beta expression in
      human brain and suggest that SAMP6 may provide insights into age-associated brain
      alterations and diseases.

PMID- 9562507
TI  - Age-related changes of calbindin-D28k, calretinin, and parvalbumin mRNAs in the
      hamster brain.
AB  - Changes of three different cytosolic Ca2+ binding proteins, calbindin-D28k,
      calretinin, and parvalbumin mRNA expression in the brain of the hamster during
      aging were investigated by in situ hybridization using brains from hamsters aged
      4, 9, 13, 19, to 24 months old. In cerebellum area, calbindin-D28k transcripts
      showed about 50% to 68% decrease in content in aged-hamster (19 and 24 months
      old) compared with young (4 months) and adult (9 months), whereas calretinin and
      parvalbumin mRNA expression remain unchanged throughout the ages examined.
      Calbindin-D28k gene expression was decreased during aging also in the hippocampus
      (approximately 60% reduction) and striatum (approximately 25%). In the same
      areas, striatum and hippocampus, calretinin and parvalbumin mRNA expression in
      the equivalent sections were not significantly changed with age. These data raise
      the possibility that CNS calbindin-D28k expression may be selectively down
      regulated during aging. The statistically significant decrease of calbindin-D28k
      mRNA in the normal aging process also suggests and provides further support for
      the hypothesis that this calcium binding protein may have an important role in
      neuronal degeneration.

PMID- 9562508
TI  - Slow axonal regrowth but extreme hyperinnervation of target muscle after suture
      of the facial nerve in aged rats.
AB  - Unilateral transection and suture of the facial nerve was performed in 60 old
      rats (20 months of age). The time course of mimetic reinnervation was studied by
      counting all retrogradely labeled motoneurons in the facial nucleus after
      injection of HRP into the whiskerpad muscles for 14-112 days post operation. The
      comparison between these neuron counts and data for young rats yielded four
      conclusions. First, the qualitative equivalent of the phenomenon "misdirected
      reinnervation" in aged rats was the same as in young adults: HRP-labeled
      motoneurons were scattered throughout the facial nucleus lacking myotopic
      organization from 18 until 112 days post operation. Second, no age-related loss
      of motoneurons was detected. Third, the axonal regrowth was delayed in aged rats.
      Fourth, the postoperative hyperinnervation (the projection of more motoneurons
      into a muscle than under normal conditions, i.e., the quantitative aspect of
      misdirected reinnervation) was more than two times higher than in young rats.
      These data may provide reasonable explanations for the poor functional recovery
      after reconstructive surgery on the facial nerve in old patients.

PMID- 9562509
TI  - Adrenergic nerve smooth endoplasmic reticulum calcium buffering declines with
      age.
AB  - Calcium buffering capacity declines with age in sympathetic nerves of rat tail
      artery. To test whether smooth endoplasmic reticulum (SER) calcium buffering
      declines with age, effects of two SER calcium-ATPase inhibitors on norepinephrine
      release and intracellular calcium were determined. Thapsigargin or cyclopiazonic
      acid caused a significant increase in stimulation-evoked norepinephrine release
      from 6 month tail arteries with much less effect in 20 months. In isolated
      superior cervical ganglion cells, the rate of rise of calcium with K+
      depolarization increased only in young cells with either cyclopiazonic acid or
      thapsigargin, with no effect in the old. In young cells, cyclopiazonic acid
      significantly influenced time to peak, rate of decline, and time to basal of K+
      evoked calcium transients, but had no effect in old cells. Thapsigargin caused a
      significant increase in rate of decline in young, but not old, cells. These
      differential effects suggest an age-related decline in function of SER calcium
      buffering mechanisms in the sympathetic nervous system causing older nerves to
      become more reliant on mitochondria to buffer calcium.

PMID- 9562510
TI  - Age-related activation of microglia and astrocytes: in vitro studies show
      persistent phenotypes of aging, increased proliferation, and resistance to down
      regulation.
AB  - Astrocytes and microglia from cerebral cortex of 3-, 6-, 12-, and 24-month-old
      F344 male rat donors showed progressively greater proliferation during primary
      culture. Microglia from aging donor brains exhibited an amoeboid-like morphology
      and express antigens characteristic of an activated state (e.g., major
      histocompatibility complex class II). Moreover, microglia from aging donors were
      less sensitive to several types of regulators. Granulocyte-macrophage colony
      stimulating factor stimulated proliferation in microglia from young, but not
      aging brains. Transforming growth factor (TGF)-beta1 inhibited astrocytic and
      microglial proliferation in cultures from young, but not aging donors. Similarly,
      the inhibition of lipopolysaccharide-induced NO production by TGF-beta1 in
      microglia was impaired in cultures from 12-month (middle-age) brains. Another
      aging change detected by middle age, increased glial fibrillary acidic protein
      (GFAP) expression, also persisted in astrocytes from 12- to 24-month-old brains,
      as evaluated by increased activity of a 5'-upstream GFAP promoter construct.
      Thus, both microglia and astrocytes originated from aging cerebral cortex
      maintain in vitro at least some of the activated phenotypes of aging glia that
      are observed in vivo. This new in vitro cell model may allow efficient analysis
      of glial age changes.

PMID- 9562511
TI  - Activated protein C resistance: What have we learned now that the dust has
      settled?
AB  - Activated protein C resistance, most often caused by a single point mutation in
      the factor V gene, is the most common hereditary coagulation abnormality
      associated with venous thrombosis. Recent studies have established risk estimates
      of thrombosis in multiple clinical settings. The impact of activated protein C
      resistance on the absolute thrombotic risk of a given individual is significantly
      influenced by the presence or absence of other acquired or congenital risk
      factors. In this paper, the complex interplay between different risk factors for
      venous thrombosis is discussed. Additionally, the potential significance for
      arterial thrombosis of activated protein C resistance, that is not due to the
      genetic variant, Glutamine 506 factor V, is discussed.

PMID- 9562512
TI  - Are non-heart-beating donors really dead?
AB  - Brain dead patients are ideal donors for organ transplantation. The lack of
      organs has aroused new interest in other kinds of patients who are called non
      heart-beating donors. In these donors the warm ischaemia time should be as short
      as possible. This problem has led to a discrepancy between a proper diagnosis of
      death and a fast organ procurement. In non-heart-beating donor protocols the
      death should be determined in an unambiguous manner that can also be accepted in
      other situations. The best solution would be to create one set of criteria of
      death that can be applied to all situations. Brain death as the criterion of
      death also in patients with asystole would serve this purpose.

PMID- 9562513
TI  - The problem of port-site metastases after laparoscopic cancer surgery.
AB  - The whole era of laparoscopic surgery for cancer began with the same optimistic
      view as for benign disease. However, port-site metastases were published as soon
      as in 1993. According to literature, it is difficult to estimate exactly the
      incidence of port-site metastases in laparoscopic colon cancer surgery. Moreover,
      there are few reports of wound recurrences after open surgery although the
      incidence is probably about 1%. There are some hypothetical explanations of
      metastases to the laparoscopic wound, which have not been solved. It can be a
      haematogenic spread to the wound. Another mechanism could be an aerosol of tumour
      cells and a third one adhesions of tumour cells to the surface of the instruments
      or ports. This editorial discusses some of the possible mechanisms of port-site
      recurrences. Also, most importantly, the justification for laparoscopic surgery
      for colon cancer is discussed. Only through randomized trials can this question
      be solved. Therefore, it is mandatory to include patients in a trial and
      colorectal cancer patients should not undergo laparoscopic surgery outside a
      clinical randomized trial.

PMID- 9562514
TI  - Mitochondrial deafness.
AB  - Hearing impairment is a common disorder, largely genetic in origin, and showing
      classical features of a heterogeneous genetic disease. Up to 100 independently
      acting nuclear genes are involved in the disorder, of which around 30 have been
      mapped, but only a handful identified. Mutations in mitochondrial DNA also play a
      significant role in both syndromic and nonsyndromic sensorineural hearing
      impairment. Environmental agents such as aminoglycoside antibiotics and as yet
      unidentified nuclear genes interact with mitochondrial mutations in the
      expression of auditory phenotypes. The spectrum of different mitochondrial
      mutations associated with hearing impairment, taken together with mechanistic
      studies at the molecular level, suggests that the pathogenic process involves the
      accumulation of abnormal translation products inside mitochondria, in sensitive
      cells of the auditory system. This leads to a prediction of the involvement of a
      novel class of nuclear genes in hearing impairment, namely those with roles in
      'mitochondrial protein quality control'.

PMID- 9562515
TI  - Strategies to identify genes for complex diseases.
AB  - Genes underlie numerous human diseases and traits. Although we have witnessed a
      great deal of success in identifying disease-susceptible genes, the task remains
      challenging for most of the complex diseases. This paper reviews evidence for the
      role of genetic factors in complex diseases including breast cancer, diabetes and
      multiple sclerosis. We then describe strategies that can potentially optimize our
      chance of success in identifying genes involved in complex diseases. Advances in
      molecular biology, particularly mapping of the human genome, statistical methods
      that provide more accurate models of complex patterns of inheritance, and basic
      medical science, which have increased our understanding of disease
      pathophysiology, will ultimately strengthen the ability of the current generation
      of genetic epidemiological studies to identify the genetic basis of complex human
      disorders.

PMID- 9562516
TI  - Pro- and anti-inflammatory cytokines in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the
      accumulation of inflammatory cells into the synovium and the destruction of
      joints. Cytokines are important regulators of the synovial inflammation. Some
      cytokines, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-1,
      function by promoting inflammatory responses and by inducing cartilage
      degradation. Other cytokines, such as IL-4, IL-10 and IL-13, function mainly as
      anti-inflammatory molecules. Although anti-inflammatory cytokines are present in
      rheumatoid joints, in progressive RA their levels obviously are too low to
      neutralize the deleterious effects of proinflammatory cytokines. Inhibiting the
      action of proinflammatory cytokines by using specific cytokine inhibitors or anti
      inflammatory cytokines is the basis for new therapies currently tested in
      patients with RA. Promising results on the use of neutralizing anti-TNF-alpha
      monoclonal antibodies in the treatment of RA have been reported. The results from
      a trial using recombinant IL-10 in the treatment of patients with RA are
      available in the near future and will be important in determining the therapeutic
      potential of this cytokine.

PMID- 9562517
TI  - Liquid-assisted ventilation: physiology and clinical application.
AB  - Liquid-assisted ventilation, as an alternative ventilation strategy for
      respiratory distress, is progressing from theory and basic science research to
      clinical application. Biochemically inert perfluorochemical liquids have low
      surface tension and high solubility for respiratory gases. From early immersion
      experiments, two primary techniques for liquid-assisted ventilation have emerged:
      total liquid ventilation and partial liquid ventilation. While computer
      controlled, time-cycled, pressure/volume-limited total liquid ventilators can
      take maximum advantage of these liquids by completely eliminating the gas phase
      in the distressed lung, partial liquid ventilation takes advantage of having
      these liquids in the lung while maintaining gas ventilation. The benefits of both
      partial and total techniques have been demonstrated in animal models of neonatal
      and adult respiratory distress syndrome, aspiration syndromes and congenital
      diaphragmatic hernia and also in combination with other therapeutic modalities
      including extracorporeal membrane oxygenation, high-frequency ventilation and
      nitric oxide. Additionally, nonrespiratory applications have expanding potential
      including pulmonary drug delivery and radiographic imaging. Since its use in
      neonates in 1989, liquid-assisted ventilation in humans has progressed to a
      variety of clinical experiences with different aetiologies of respiratory
      distress. The future holds the opportunity to clarify and optimize the potential
      of multiple clinical applications for liquid-assisted ventilation.

PMID- 9562518
TI  - Immunodeficiencies and haematological disorders--direct connections to cellular
      signalling pathways.
AB  - Extracellular signals, such as cytokines and foreign antigens, regulate the
      development and activation of haematopoietic cells through receptor-mediated
      transcriptional responses. Investigation of the biochemical events that transduce
      receptor activation to intracellular signal transduction have revealed a general
      mechanism for both the antigen receptor and the cytokine receptor nuclear
      signalling. Receptor stimulation is coupled to down-stream signalling cascades
      through activation of cytoplasmic tyrosine kinases but both receptor types
      utilize distinct signalling proteins. Antigen receptors employ protein tyrosine
      kinases of the Src, Syk, and Tec families which phosphorylate and activate
      cytoplasmic signalling proteins leading to activation of NF-AT, AP-1 and NF
      kappaB transcription factors, while the principal signal transducers for cytokine
      receptors are the Jak tyrosine kinases and Stat transcription factors. The
      molecular basis for several immune and haematological disorders has been
      characterized during the last few years and they have been found to be caused by
      defects in various signalling proteins. In this review the aetiology of immune
      and haematological disorders is discussed in the light of the recent developments
      in signal transduction.

PMID- 9562519
TI  - Epidermal growth factor receptor in mice and men--any applications to clinical
      practice?
AB  - The epidermal growth factor receptor (EGF-R) is perhaps the best studied member
      of tyrosine kinase receptors. Its inactivation by homologous recombination
      results in three different phenotypes ranging from peri-implantation lethality to
      postnatal lethality. The mildest form of EGF-R inactivation leads to epithelial
      immaturity and postnatal death due to respiratory failure and necrotizing
      enterocolitis-like lesions in the intestine. The defects seen in this 'postnatal
      lethality phenotype' manifest in the classical EGF-responsive organs (skin,
      intestine) and organs undergoing branching morphogenesis during development
      (lung, kidney, mammary gland, pancreas and prostate), and thus accord with the
      concept of EGF family members being important epithelial mitogens. The
      respiratory failure of the EGF-R (-/-) mice results from impaired branching of
      the alveolar tree and leads to decreased surface for gas exchange. Overall, the
      lung phenotype bears similarity to respiratory distress syndrome and
      bronchopulmonary dysplasia--the most common complications of prematurity in
      humans. Intestinal changes seen in the EGF-R (-/-) mice vary in severity, the end
      point being severe mucosal lesions and necroses. These findings resemble those
      seen in necrotizing enterocolitis of premature babies, a serious intestinal
      problem in the neonate. Although deficient EGF-R function is not the reason for
      these prematurity-associated diseases it may nevertheless exacerbate them.
      Potential usage of EGF transforming growth factor-alpha in clinical work is
      discussed.

PMID- 9562520
TI  - The role of bronchoalveolar lavage in the microbiological diagnosis of pneumonia
      in patients with haematological malignancies.
AB  - In the aetiological diagnosis of pulmonary infections in patients affected by
      haematological malignancies we evaluated the utility of bronchoalveolar lavage
      (BAL). One hundred and twenty-seven BAL were performed in 119 patients. In our
      series, we identified the agent of pneumonia in 53.5% of episodes with the best
      results in aspergillosis, very common in these patients. The previous empirical
      anti-infective treatment was modified in 14 episodes (11%). The procedure was
      generally well tolerated and only one patient bled. We maintain that BAL is a
      useful diagnostic tool for detecting the agents of pulmonary infections in
      patients with haematological malignancies, especially when the routine
      microbiological procedures fail, and it also represents a good alternative to
      more invasive procedures.

PMID- 9562521
TI  - Tracking of serum lipoprotein (a) concentration and its contribution to serum
      cholesterol values in children from 7 to 36 months of age in the STRIP Baby
      Study. Special Turku Coronary Risk Factor Intervention Project for Babies.
AB  - We investigated the tracking phenomenon of serum lipoprotein (a) concentrations
      and assessed the impact of serum concentration of lipoprotein (a) cholesterol on
      total cholesterol concentrations in children from 7 to 36 months of age. Serum
      samples for lipoprotein (a) and cholesterol determinations at 7, 13, 24 and 36
      months were prospectively obtained from 430 children. Serum lipoprotein (a) was
      determined using immunoradiometric assay. A strong correlation was observed
      between lipoprotein (a) concentrations at 7 and 36 months of age (r = 0.88, P <
      0.001). Seventy-eight per cent to 86% of the children in the lowest and highest
      lipoprotein (a) quintiles at 13 months remained in the respective quintiles at 36
      months. The average contribution of lipoprotein (a) cholesterol to total
      cholesterol varied from 0.5% to 3.2% (individual variation 0.13-32.39%) depending
      on the type of milk received and the age of the children. At 7 months the
      contribution was 0.44% in breast-fed and 0.93% in formula-fed infants (P <
      0.0001). The tracking phenomenon of serum lipoprotein (a) concentrations is
      strong already in early childhood. The contribution of lipoprotein (a)
      cholesterol to serum total cholesterol concentration should be taken into account
      when the changes in serum cholesterol levels are interpreted in the first year of
      life.

PMID- 9562522
TI  - Gene therapy of single-gene disorders: preface to the special section.
AB  - Gene therapy was introduced into clinical practice with great excitement, much
      publicity and considerable optimism in the early 1990s. Scientific evaluation of
      the early clinical trials has, however, greatly reduced the initial optimism.
      Follow-up studies have revealed that many early gene therapy trials mainly
      represented gene transfer into patients, possibly with short-term effects, but
      not true gene therapy where the course of the disease is permanently affected.
      This has lead to critical re-evaluation of the approaches taken. Clearly, more
      basic understanding is needed of the molecular mechanisms of the diseases
      treated. For this purpose, better animal models for human diseases are necessary.
      One of the biggest obstacles for gene therapy has been the lack of adequate
      vector systems. Development of new vectors for efficient and targeted delivery
      and uptake of therapeutic genes is a crucial area where progress needs to be
      made. The rationale for gene therapy depends largely on the type of disease to be
      treated. Recessively inherited single-gene disorders represent diseases where the
      concept of gene therapy--addition of a therapeutic gene to restore the lost
      function of two mutant alleles--is easily understood and rarely questioned.
      However, most gene therapy protocols are focused on multifactorial diseases such
      as malignancies where the therapeutic approach is quite different. While gene
      transfer technologies are being developed into truly effective gene therapy, the
      fight against inherited single-gene disorders also continues at population level
      by carrier screening and prenatal diagnostics where rapid methodological
      developments are taking place.

PMID- 9562523
TI  - Molecular background of the Finnish disease heritage.
AB  - Finland has a population with a history revealing features of founder effect,
      genetic drift and isolation. Relatively small founder populations have slowly
      inhabited a large country and internal isolates have developed within Finland.
      This is reflected even today in the regional enrichment of some diseases
      belonging to the Finnish disease heritage. This concept was launched before the
      DNA era by skillful clinicians and today it comprises some 30 diseases with a
      wide variety of clinical phenotypes. Special strategies have been adapted in the
      initial locus assignment and in the restriction of the critical chromosomal DNA
      region having so far resulted in the successful isolation of 11 disease genes.
      Detailed analyses of these disease genes and their function have provided new
      insights into the structure and function of defective proteins as well as into
      the biology of affected tissues.

PMID- 9562524
TI  - The beta-hexosaminidase deficiency disorders: development of a clinical paradigm
      in the mouse.
AB  - Tay-Sachs disease and Sandhoff disease are severe neurodegenerative disorders
      caused by a deficiency of beta-hexosaminidase A and resultant accumulation of its
      substrate, GM2 ganglioside, in neuronal lysosomes. The three clinical forms of
      the disorders (infantile, juvenile and adult) are of varying severity and onset,
      and have been correlated with the amount of residual GM2 ganglioside-degrading
      activity present in patients' cells. Through targeted disruption of the murine
      beta-hexosaminidase genes in embryonic stem cells, we have developed a set of
      mice that vary in their GM2 ganglioside-degrading capacity and exhibit many of
      the clinical features of the human diseases. These mice are valuable for the
      study of pathogenic mechanisms and for devising novel therapeutic strategies in
      these disorders.

PMID- 9562525
TI  - Animal model for fragile X syndrome.
AB  - The fragile X syndrome, one of the most common forms of inherited mental
      retardation, is caused by an expansion of a polymorphic CGG repeat upstream of
      the coding region in the FMR1 gene. The expansion blocks expression of the FMR1
      gene due to methylation of the FMR1 promoter. Functional studies on the FMR1
      protein have shown that the protein can bind RNA and might be involved in
      transport of RNAs from the nucleus to the cytoplasm. A role of FMR1 protein on
      translation of certain mRNAs has been suggested. An animal model for fragile X
      syndrome exists and these mice show some behavioural difficulties mimicking the
      human fragile X syndrome phenotype. This review presents what is known about the
      protein and what is learned from the animal model for fragile X syndrome.

PMID- 9562526
TI  - Ion channel mutations in mouse models of inherited neurological disease.
AB  - Analysis of the molecular defects in mouse mutants can identify candidate genes
      for human neurological disorders. During the past 2 years, mutations in sodium
      channels, calcium channels and potassium channels have been identified by
      positional cloning of the spontaneous mouse mutants motor endplate disease,
      tottering, lethargic and weaver. The phenotypes of four allelic mutations
      identified in the sodium channel gene Scn8a range from ataxia and muscle weakness
      through severe dystonia and progressive paralysis, indicating that human
      mutations in this gene could be associated with a variety of clinical syndromes.
      Mutations of the calcium channel subunits beta 4 in the lethargic mouse and alpha
      1A in the tottering mouse have specific effects on cerebellar function. Targeted
      mutation of ligand-gated ion channels has also been used to generate new models
      of neurological disease. We will review these recent achievements and their
      implications for human neurological disease. The mouse studies indicate that
      mutations in ion channel genes are likely to be responsible for a broad spectrum
      of clinical phenotypes in human neurological disorders.

PMID- 9562527
TI  - The road toward human gene therapy--a 25-year perspective.
AB  - The concept of human gene therapy arose in the early 1970s and has now been the
      subject of many clinical trials in human patients. To date, there have been no
      truly convincing therapeutic successes, but any disappointment with that fact is
      due more to the exaggerated levels of our expectations than to any failure of
      concept. The concept of human gene therapy has been a startling success and it is
      now one of the most important driving forces in medicine. Current tools have
      simply not been adequate for the difficult job of efficient and stable gene
      delivery, faithful and regulated gene expression and clinical correction of a
      human disease. Nevertheless, progress toward human gene therapy is rapid and
      inexorable and the second phase of human gene therapy, the implementation phase,
      will soon also succeed.

PMID- 9562528
TI  - An academic centre for gene therapy research with clinical grade manufacturing
      capability.
AB  - Huddinge University Hospital is a major teaching hospital affiliated with the
      Karolinska Institute in Southern Stockholm. For the past few years several groups
      have been working there in different areas of gene therapy relating to cancer,
      genetic and infectious diseases. However, a facility to produce clinical grade
      material under good manufacturing practice was lacking. To this end, Huddinge
      University Hospital has taken the initiative to open a Gene Therapy Research
      Center in 1996. This facility, which is unique of its kind in Scandinavia, is
      located in the Novum Research Park, Huddinge, and is a part of the existing
      Clinical Research Center. The newly built centre will allow clinicians and
      researchers to develop and produce vectors (viral and nonviral) for clinical
      trials and do basic research to understand the mechanisms of diseases. Although
      the centre will primarily serve the academic institutions it will also extend its
      facilities to other investigators in this field. The production unit is run in
      collaboration with the Faculty of Medicine, University of Lund. On-going projects
      include production of plasmid vectors for prevention of postangioplasty
      restenosis, DNA vaccine for HIV-1, cationic liposome DNA complexes for cystic
      fibrosis and retroviral vectors for HIV-1.

PMID- 9562529
TI  - Locked on target: strategies for future gene diagnostics.
AB  - A rapidly expanding number of genetic mechanisms contributing to disease can be
      accessed via molecular analysis. In order to take full advantage of this
      potential for genetic diagnostics, and to monitor treatment by gene therapy and
      other emerging methods, a new generation of diagnostic techniques will be
      required. Of central importance in future analyses is the possibility to perform
      very large numbers of simultaneous genetic analyses in analytical devices of
      small linear dimensions. We have developed a new molecular probe design that is
      amenable to highly multiplex, specific analyses of total genomic DNA or of RNA
      molecules expressed in tissue samples. Here, a brief history of gene analytical
      procedures is presented, followed by a discussion of the properties, means of
      synthesis and applications of this new class of gene analytic reagents, padlock
      probes.

PMID- 9562530
TI  - Delivering genetic screening to the community.
AB  - Concern is often expressed that, in the future, screening for genetic risk will
      become too widespread. Haemoglobin disorders (the thalassaemias and sickle cell
      disorders) offer an excellent model for genetic screening, because they are
      common and severe. They are recessively inherited. Carriers can be detected by
      conventional blood tests with an accuracy of 99%, so couples at risk can be
      identified before they have children and offered genetic counselling and prenatal
      diagnosis. Carrier-screening programmes have been in place in several countries
      for over 20 years and now offer extensive practical experience of the problems of
      delivering the service equitably to entire populations. This experience suggests
      that the main risk is of too little rather than too much genetic screening, and
      of doing it badly, and demonstrates the need for a discipline of 'community
      genetics'. Here I propose that modern information technology has a central role
      in providing communities with adequate access to correct genetic information.

PMID- 9562532
TI  - Neonatal otoacoustic emissions recorded using maximum length sequence stimuli.
AB  - OBJECTIVE: Maximum length sequence (MLS) stimulation allows transient evoked
      otoacoustic emissions (TEOAEs) to be recorded at very high stimulation rates.
      Previous work has focused on recording from normally hearing adult subjects; the
      aim of this study was to obtain information about emissions recorded using this
      technique from newborns and to compare these results with those obtained from
      adults. The feasibility of recording from newborns on the postnatal wards also
      was addressed. DESIGN: The study comprised two parts. In the first, TEOAEs were
      collected at 13 stimulation rates from a selected group of babies. The second
      part of the study comprised only two stimulation rates, a conventional rate of 40
      clicks/sec and the maximum MLS rate of 5000 clicks/sec. RESULTS: The neonatal MLS
      TEOAEs behave in a similar manner to those obtained from adult subjects. The
      morphology of the waveforms was similar for the conventional and MLS TEOAEs. As
      the stimulus rate increases, the amplitude of the emission decreases, reaching an
      approximate plateau by 1000 to 2000 clicks/sec. The absolute reduction in
      amplitude seen at the high MLS rate is related to the amplitude of the
      conventional TEOAE but is always approximately the same when expressed as a
      percentage or proportion of that amplitude. CONCLUSION: The theoretical
      advantages of speed and sensitivity seen for adult subjects also should hold true
      for the neonatal population. Although the system used to test was a prototype
      with none of the refinements found in commercial systems, it was possible to
      record adequate emissions from a ward-based population of newborns.

PMID- 9562531
TI  - Field sensitivity of targeted neonatal hearing screening using the Nottingham ABR
      Screener.
AB  - OBJECTIVE: A population of children having bilateral moderate to profound hearing
      impairment was investigated to find out the number who passed (false negatives)
      and who failed (true positives) a screening test based on the auditory brain stem
      response (ABR). DESIGN: This study of the ABR is a parallel report to Lutman,
      Davis, Fortnum, and Wood (1997), where the transient evoked otoacoustic emission
      was examined on a similar but not identical population of at-risk neonates.
      Hearing screening was undertaken in at-risk neonates (targeted screening) at
      seven hospitals in the UK using the Nottingham ABR Screener. During the period
      from January 1988 to December 1993, a total of 6983 neonates had been tested.
      Assessment of audiological records from the participating centers ascertained
      that 201 children born between January 1988 and December 1993 had hearing
      threshold levels in both ears of 50 dB or more, averaged over the speech
      frequencies 0.5, 1, 2, and 4 kHz. Of these, 51 had completed the ABR screening
      test. Examination of the ABR records, which included both machine and visual
      scoring, indicated whether they had passed or failed the screening test. RESULTS:
      Forty-six of the 51 hearing impaired babies failed the neonatal ABR screen either
      on one or both ears (five false negatives), and 42 failed the test on both ears
      (nine false negatives). This resulted in field sensitivities of 90% and 82%,
      respectively. Two cases of suspected progressive hearing loss have been included
      in the numbers of false negative results. The percentage of babies passing the
      screen on both ears and subsequently having normal hearing (specificity) is
      typically 93%. CONCLUSIONS: Neonatal hearing screening in an at-risk population
      using a highly automated ABR test is a viable and effective tool for
      identification of hearing impairment. Although the field sensitivity of the test
      is high, it is unable to identify all babies with a criterion level of hearing
      loss. There are a number of possible explanations as to the origin of false
      negative results: configuration of the pure-tone audiogram, a progressive hearing
      loss, acquired sensorineural or conductive loss, retrocochlear deafness, or an
      incorrect interpretation of the screening test. Passing a neonatal screening
      test, therefore, does not exclude the possibility of subsequent hearing
      impairment and highlights the need for further surveillance.

PMID- 9562533
TI  - Age and the human cochlear traveling wave delay.
AB  - OBJECTIVE: Cochlear physiologic changes that occur with aging also may affect the
      mechanics and filtering properties of the cochlea. In studying aging effects, it
      is also necessary to consider the effects of hearing threshold losses because
      thresholds generally increase with age, and threshold losses also affect the
      filtering properties of the cochlea. A distortion product emission (DPE)-based
      measurement of human cochlear traveling wave delays allows an indirect assessment
      of the mechanics of the traveling wave and how it might change with age. DESIGN:
      The cochlear traveling wave delay has been derived from DPE phase measurements
      using an f1 sweep paradigm (Kimberley, Brown, & Eggermont, 1993). In the present
      study, traveling wave delay was estimated from DPE phase measurements taken from
      the left ears of 91 subjects (22 to 78 yr) with auditory thresholds ranging from
      normal hearing (< or = 25 dB SPL, ANSI 1969) to mild cochlear hearing damage. No
      one under the age of 65 had hearing losses exceeding 40 dB SPL to 8 kHz. Pure
      tone thresholds were determined at eight frequencies through a 4-interval, forced
      choice, adaptive-level psychophysical test. DPE phase and amplitude measurements
      were made at these eight frequencies using CUBeDIS-related software (AT&T Bell
      Labs). Round-trip traveling wave estimates were calculated from the DPE phase
      measurements for each of the eight f2 frequencies (places). RESULTS: Traveling
      wave delays estimated using DPE phase were not significantly affected by mild
      hearing losses. Traveling wave delay, however, does increase slightly with age.
      Optimal f2/f1 ratio and associated DPE amplitude also were tested for age or
      threshold effects. The optimal f2/f1 ratio remained unaffected by age or hearing
      loss but decreased with increasing frequency. The maximum DPE amplitude decreased
      with both advancing age and increasing pure-tone threshold, so it was impossible
      to isolate the contribution of each individual factor. CONCLUSIONS: Mild hearing
      losses do not affect the round-trip traveling wave delay. There is a slight age
      dependence, however. This may suggest that there are age-related but threshold
      independent factors that may alter such properties as basilar membrane stiffness
      or cochlear fluid composition. The relationship between maximum DPE amplitude and
      threshold, at the frequencies tested, is a better predictor of hearing thresholds
      than the DPE amplitude as obtained from a fixed ratio DPE amplitude measurement.

PMID- 9562534
TI  - Acquisition of noise-induced hearing loss by railway workers.
AB  - OBJECTIVE: The rate of growth of hearing loss was examined in a population of
      workers exposed to noise. Of special interest was the course of loss in the first
      10 yr of work, for which international standards provide little information.
      Based on the International Standards Organization (ISO) 1999 compilation, it was
      hypothesized that the proportional growth of hearing loss would be constant in
      log years. DESIGN: Of 5000 workers compensated for hearing loss by a railroad,
      500 were selected at random for analysis. For these workers, 2660 audiograms were
      available. The audiograms were distributed unsystematically over work careers,
      and for most workers were sparsely distributed. Thresholds were age corrected
      using ISO 1999 Annex B and averaged as a function of years on the job for two
      partitions, 0.5, 1, 2, and 3 kHz and 2 and 4 kHz. The average curves were
      compared with projections based on the ISO 1999 data as suggested by Dobie
      (1993a). A subset of workers with substantial hearing loss when hired was
      examined to evaluate the effect of pre-existing hearing loss. RESULTS: Hearing
      was worse at hire for this sample of workers than suggested by ISO 1999 Annex B
      for an unscreened sample of the general population at comparable ages. As a
      result, the early hearing loss was underpredicted by the ISO 1999 projection.
      Except at the earliest years of employment, the rate of growth toward the final
      hearing loss for the mean of the sample of workers was approximated by the
      projection from ISO 1999. The ISO 1999 projection is based on growth of the
      percentage of loss at the final audiogram obtained each year. In subgroups of
      workers, i.e., for the lower quartile and for the upper quartile of the sample,
      the projection based on ISO 1999 was similarly effective. Workers hired with
      prior loss showed growth of hearing loss that was flatter than that of either the
      mean of all workers or the ISO 1999 projection, but the growth curve for these
      workers approximated the average curve shifted to later years to bring the
      initial loss into correspondence with the predicted loss. CONCLUSIONS: For a
      group of workers exposed to a noisy environment, growth of hearing loss can be
      projected fairly well based on ISO 1999, without knowledge of the details of
      spectrum or level of noise exposure. This suggests that it would be possible to
      allocate the percentage of a known total hearing loss acquired in a group of
      workers on a year-by-year basis, given knowledge of work history for a claimant
      population in the absence of detailed knowledge of the exposure or detailed
      sequential audiometric data.

PMID- 9562535
TI  - A comparison of threshold-based fitting strategies for nonlinear hearing aids.
AB  - OBJECTIVE: In recent years, wide dynamic range compression (WDRC) has been used
      with increasing success. To optimize the fit with this type of hearing aid
      circuitry, subjective measures of loudness growth often are used. Unfortunately,
      these type of measures cannot be performed with infants, young children, and some
      elderly individuals. The primary purpose of this study was to compare the fitting
      recommendations of two recently described threshold-based procedures for fitting
      nonlinear hearing aids (DSL 4.0 and FIG6) to the use gain settings of satisfied
      adult hearing aid users for whom the fitting was based on subjective measures of
      loudness growth. Because it cannot be assumed that the use settings for adults
      will be appropriate for young children, a secondary goal was to quantify the
      audibility of speech at the use settings derived from loudness growth measures.
      DESIGN: Forty-nine adult hearing aid users with mild to severe sensorineural
      hearing loss participated in this study. For all subjects, loudness growth
      measures were used to optimize the fit of a 2-channel WDRC hearing aid. The use
      gain at 50 and 80 dB SPL was compared with the gain recommended by DSL, FIG6, and
      the manufacturer's threshold-based fitting algorithm. RESULTS: In general, both
      DSL and FIG6 prescribed more gain than actually was used by these hearing aid
      wearers. These discrepancies increased as a function of frequency, and
      differences in excess of 20 dB were observed in some cases. The manufacturer's
      algorithm provided a closer approximation to the use gain than either DSL or
      FIG6. Utilizing these use gain values, an Aided Audibility Index (AAI) was
      calculated for soft, average, and loud speech across four degrees of hearing
      loss, ranging from mild to severe (12 conditions). Transfer functions for
      continuous discourse and nonsense syllables were applied to yield estimated
      intelligibility scores. For the higher context speech materials, estimated
      intelligibility was > or = 85% for nine of the 12 conditions. For low-context
      speech materials, estimated intelligibility was > or = 85% for only three of the
      12 conditions. CONCLUSIONS: Results suggest that the gain recommendations
      provided by both DSL and FIG6 exceeded the gain actually used by the adult
      hearing-impaired subjects in this study. Gain recommendations from the
      manufacturer's algorithm provided a closer approximation to the use gain values
      of these subjects. These findings suggest that, for adult hearing aid users who
      cannot perform loudness judgments reliably, the manufacturer's algorithm would be
      expected to provide a closer approximation to loudness-based use gain values than
      either DSL or FIG6. However, AAI calculations revealed that the gain
      recommendations from this algorithm produce adequate audibility of speech only if
      one assumes linguistic competence. When AAI values are transformed to predict the
      intelligibility of low-context speech materials, it appears that the degree of
      audibility may not be appropriate for prelingually hearing-impaired children with
      more than a moderate hearing loss.

PMID- 9562536
TI  - Accuracy of predicted ear canal speech levels using the VIOLA input/output-based
      fitting strategy.
AB  - OBJECTIVE: The Visual Input/Output Locator Algorithm (VIOLA) is a software
      assisted method for prescribing amplification targets and selecting a hearing aid
      to match the targets. Although the procedure calls for selection and fitting of
      hearing aids in terms of their pure-tone input/output functions in a coupler, it
      is assumed that a hearing aid that matches the coupler prescription targets will
      produce specific amplified speech levels in the patient's ear canal. This
      investigation evaluated the validity of that assumption. DESIGN: Six hearing aids
      were evaluated. They were representative of linear and compression processing as
      well as single- and 2-channel designs. The "subject" was a KEMAR manikin with
      realistic assumed hearing loss and loudness perception characteristics. Each
      hearing aid was configured to match the subject's VIOLA prescription as closely
      as possible. Predicted ear canal speech levels were determined using the
      prescription rules and modified by the differences between coupler prescription
      targets and coupler performance of the actual hearing aids. With the subject
      wearing each hearing aid coupled to an unvented earmold, continuous speech was
      presented in the sound field and measured, after amplification, in the ear canal.
      The match between observed and predicted levels of amplified speech indicated the
      validity of the VIOLA assumptions under examination. RESULTS: The match between
      predicted and observed levels was good for soft speech input levels. As speech
      input levels increased, the differences between observed and predicted levels
      also increased, with the largest differences seen for loud speech inputs. When
      differences were seen between observed and predicted levels, they were always in
      the direction of lower than predicted ear canal levels. The differences between
      observed and predicted levels were attributed to the effects of limiting, effects
      of compression ratio in wide range compression, the individual subject's field-to
      microphone transfer function, and the subject's individual real-ear-to-coupler
      level difference. CONCLUSIONS: Ear canal speech levels were reasonably close to
      predicted values, and the deviations from predicted levels were plausibly
      accounted for by consideration of hearing aid performance. Thus, the approach
      used by the VIOLA procedure holds considerable promise for extending clinical
      control over the complex and interactive parameters of nonlinear hearing aids.
      The results of this study indicate that selection and fitting of hearing aids
      using the current VIOLA procedure usually will result in the generation of lower
      than predicted ear canal speech levels, especially for loud speech inputs.
      However, the accuracy of the procedure could be improved substantially by
      modification of the software to account for the effects of limiting and those of
      the compression ratio in systems with compression thresholds lower than the level
      of unamplified loud speech.

PMID- 9562537
TI  - The effects of processor strategy on the speech perception performance of
      pediatric nucleus multichannel cochlear implant users.
AB  - OBJECTIVE: The present investigation examined the speech perception skills of
      pediatric cochlear implant users who changed from their original speech
      processors and strategies to the Spectral Peak (SPEAK) strategy. DESIGN: A within
      subjects design was used to compare individual subject's performance using the
      SPEAK strategy with that obtained with their previous speech strategy (FOF1F2 or
      Multipeak) in this retrospective study. The subjects demonstrated a wide range of
      perceptual abilities and had used a cochlear implant for varying lengths of time
      before converting to the SPEAK strategy. RESULTS: Nine of the 11 subjects showed
      significant improvement on at least one of the open-set word recognition
      measures, whereas two subjects showed no change on any of the open-set measures
      when using the SPEAK strategy. CONCLUSIONS: The present results suggest that the
      majority of pediatric cochlear implant users are likely to show improved speech
      perception performance when converting to the new SPEAK processing strategy.

PMID- 9562538
TI  - The identification of consonants and vowels by cochlear implant patients using a
      6-channel continuous interleaved sampling processor and by normal-hearing
      subjects using simulations of processors with two to nine channels.
AB  - OBJECTIVE: To compare the vowel and consonant identification ability of cochlear
      implant patients using a 6-channel continuous interleaved sampling (CIS)
      processor and of normal-hearing subjects using simulations of processors with two
      to nine channels. DESIGN: Subjects, 10 normal-hearing listeners and seven
      cochlear implant patients, were presented synthetic vowels in /bVt/ context,
      natural vowels produced by men, women, and girls in /hVd/ context, and consonants
      in /aCa/ context for identification. Stimuli for the normal-hearing subjects were
      pre-processed through simulations of implant processors with two to nine channels
      and were output as the sum of sinusoids at the center frequencies of the analysis
      filters. RESULTS: Five implant patients' scores fell within the range of normal
      performance with a 6-channel processor when the patients were tested with
      synthetic vowels. Four patients' scores fell within the range of normal with a 6
      channel processor when the patients were tested with multitalker vowels. Five
      patients' scores fell within the range of normal for a 6-channel processor for
      the consonant feature "place of articulation." CONCLUSION: Signal processing
      technology for cochlear implants has matured sufficiently to allow some patients
      who use CIS processors and a small number of monopolar electrodes to achieve
      scores on tests of speech identification that are within the range of scores
      established by normal-hearing subjects listening to speech processed through a
      small number of channels.

PMID- 9562539
TI  - Multiple bilaterally asymmetric cortical sources account for the auditory N1m
      component.
AB  - The hypothesis that the N1, the major negative component of the cortical evoked
      response to auditory stimuli, originates from the primary auditory cortex has
      been supported by several studies. In a previous study we showed that, when
      monaural stimulation with pure tones is used, the distribution of the N1 peak
      over the scalp could be accounted for by successive activation of adjacent
      sources on the floor of the Sylvian fissure. In an attempt to establish the
      generality of the phenomenon, in this study we investigated further the
      generation of the N1 component using a variety of auditory stimuli, including
      pure tones, complex sounds (musical notes), and words, as well as binaural
      stimulus presentation. Additionally, we used a new recording system which allows
      recording of the distribution of the magnetic flux over the entire head
      simultaneously, thus eliminating the need for multiple recording sessions and the
      related problems of habituation and of changes in attention level. We found that
      a series of single dipolar sources could account for the entire duration of the
      N1m component. The location of the sources fell within the primary auditory
      cortex and, during the evolution of the component, they followed a posterior
      anterior, medial-lateral, superior-inferior trajectory, bilaterally, along the
      superior surface of the temporal lobes. Additionally, the distribution of N1
      sources on the two hemispheres showed a marked asymmetry, with the right
      hemisphere sources covering a larger area. The established consistency of
      successive source excitation across subjects, studies, types of stimuli, and
      recording systems, as well as the newly demonstrated hemispheric asymmetry of
      source extent, suggest the presence of a reliable phenomenon indicative of the
      functional organization of the auditory cortex.

PMID- 9562540
TI  - Spatial enhancement of event-related potentials using multiresolution analysis.
AB  - Multiresolution analysis is a potentially useful tool to enhance the brain's
      electrical fields (spatial distributions of event-related potentials (ERP)), and
      to bring out spatial features which may not be seen in the fields before
      enhancement. For comparing different images (slices from ERP of different
      subjects or from the same subject but evoked by different stimuli), we define a
      measure (surface energy) at each decomposition scale and for different wavelets.
      The best wavelet and the best level for comparing the given images can be chosen
      based on this measure. Our experiments show that for very similar images, their
      difference can be brought out at some scale level. Three preprocessing steps are
      needed in order to carry out this wavelet analysis. First, a wavelet denoising
      step is needed to remove noise from the raw ERP. Secondly, a one-to-one mapping
      is needed to map scalp surface into a square, because the current wavelet
      analysis theory and algorithm are constructed on regular domains. Finally, a
      fitting or interpolation step is needed to construct an image on a regular grid
      in order to apply the fast wavelet transform algorithms.

PMID- 9562541
TI  - Response- and stimulus-related ERP asymmetries in a tonal oddball task: a
      Laplacian analysis.
AB  - Previous studies have found greater P3 amplitude over right than left hemisphere
      sites in a tonal oddball task with a reaction time (RT) response. This asymmetry
      had a central topography, and interacted with response hand. Identification of
      the processes underlying these asymmetries requires the use of additional methods
      for separating response- and stimulus-related contributions. We applied local
      Hjorth and spherical spline algorithms to compute surface Laplacian topographies
      of ERP data recorded from 30 scalp electrodes in a pooled sample of 46 right
      handed healthy adults. For both methods, the current sources underlying the late
      positive complex were largest at medial parietal regions, but were asymmetric at
      central and frontocentral sites. Although a frontocentral sink contralateral to
      the response hand contributed to the asymmetry of the classic P3 peak, the source
      asymmetry was most robust after the sink had resolved. The late source was
      largest at electrode C4 for right hand responses, and was further enhanced in
      subjects showing a dichotic left ear advantage, but was unrelated to response
      speed. We conclude that the right hemisphere source reflects an interaction of
      response-related asymmetries with right hemisphere processes responsible for
      pitch discrimination.

PMID- 9562543
TI  - EEG mapping in children with different dermatoglyphic patterns.
AB  - This study is an attempt to analyze the relationships between EEG and
      dermatoglyphic patterns (DP) in 6-8 years girls. EEG-mapping was carried out in
      80 healthy girls with different types of DP in 6 frequency band: delta, theta,
      alpha-1, alpha-2, alpha-3 and beta. Certain connection of the palmar and finger
      patterns with the EEG characteristics was revealed. The most pronounced
      differences were observed between subgroups with prevalence (8 and more) or
      absence of whorls on their hands fingertips, and between groups with presence or
      absence of certain pattern (whorl, loop or vestige) on thenar/interdigital 1 area
      (Th/1). Significant (p<0.05) increase of spectral density in alpha-2 and alpha-3
      bands in children with whorls on hand fingertips were revealed in the first case.
      EEG of children with Th/1 pattern differed from the group without such pattern by
      increased spectral density in alpha-2, alpha-3 and beta bands. The new data
      obtained support the genetic determination of the EEG.

PMID- 9562542
TI  - Do QEEG topographic map data have a multivariate normal distribution?
      Implications for tests of individual maps.
AB  - The study was designed to test whether topographic map data expressed in log
      power units have a multivariate normal (MVN) distribution in a healthy
      population, and to determine if any deviation from normality poses serious
      difficulties for the use of standard multivariate statistical tests in assessing
      the significance of deformations of the map in individual cases. Data on 361
      healthy adults using 20 electrodes in the classic 10/20 configuration were
      recorded in six frequency bands. The log-transformed power data were shown to
      deviate markedly from MVN. The actual distributions of multivariate tests were
      computed for the sample using the 'jackknife' method, and shown to deviate
      markedly from the F-distributions that would be expected for MVN data. These
      'jackknife' sampling distributions were then used to demonstrate significant
      deformations in the topographic maps of a patient who had sustained traumatic
      head injury.

PMID- 9562544
TI  - Visual evoked magnetic responses to central and peripheral stimulation:
      simultaneous VEP recordings.
AB  - Visual evoked magnetic field (VEF) and visual evoked potentials (VEP) in response
      to pattern reversal left half-field central (0-2 degrees, 0-5 degrees) and to
      left half-field peripheral stimulation (2-15 degrees, 5-15 degrees) were
      simultaneously recorded in 10 normal subjects. The aim was to localize the origin
      of the largest wave around 100 ms. By comparing the magnetic evoked 100m wave and
      electric evoked P100 wave, we found that the response to the small central field
      (0-2 degrees) stimulation was clearly evident in the VEP and not in the VEF,
      while the response to the peripheral field (2-15 degrees, 5-15 degrees)
      stimulation was clearly present in both the VEP and VEF. Our findings show that
      in contrast to the already recognized predominantly macular origin of VEP
      activity, VEF activity has a peripheral rather than macular prevalence. Our VEF
      findings are related to the retinotopic organization of the visual cortex; the
      100m dipole to the central field (0-5 degrees) was localized more (1.04 +/- 0.84
      cm) posterior than was the 100m dipole to peripheral stimulation (5-15 degrees).
      The localization of 100m dipoles superimposed on magnetic resonance images (MRI)
      to central stimuli showed interindividual variations that were in agreement with
      the known variability of the central field representation in the striate cortex:
      on the convexity of the occipital pole, in the outer surface of the occipital
      lobe, and around the calcarine fissure of the right hemisphere. In contrast,
      following peripheral stimulation, the 100m dipole was located along the medial
      surface of the hemisphere or in the calcarine fissure. Our results suggest that
      the main origin of the largest wave around l00ms in response to pattern reversal
      stimuli is in the striate cortex.

PMID- 9562545
TI  - A combinatorial distance-constraint approach to predicting protein tertiary
      models from known secondary structure.
AB  - BACKGROUND: Distance geometry methods allow protein structures to be constructed
      using a large number of distance constraints, which can be elucidated by
      experimental techniques such as NMR. New methods for gleaning tertiary structural
      information from multiple sequence alignments make it possible for distance
      constraints to be predicted from sequence information alone. The basic distance
      geometry method can thus be applied using these empirically derived distance
      constraints. Such an approach, which incorporates a novel combinatoric procedure,
      is reported here. RESULTS: Given the correct sheet topology and disulfide
      formations, the fully automated procedure is generally able to construct native
      like Calpha models for eight small beta-protein structures. When the sheet
      topology was unknown but disulfide connectivities were included, all sheet
      topologies were explored by the combinatorial procedure. Using a simple geometric
      evaluation scheme, models with the correct sheet topology were ranked first in
      four of the eight example cases, second in three examples and third in one
      example. If neither the sheet topology nor the disulfide connectivities were
      given a priori, all combinations of sheet topologies and disulfides were explored
      by the combinatorial procedure. The evaluation scheme ranked the correct topology
      within the top five folds for half the example cases. CONCLUSIONS: The
      combinatorial procedure is a useful technique for identifying a limited number of
      low-resolution candidate folds for small, disulfide-rich, beta-protein
      structures. Better results are obtained, however, if correct disulfide
      connectivities are known in advance. Combinatorial distance constraints can be
      applied whenever there are a sufficiently small number of finite connectivities.

PMID- 9562546
TI  - A single dipeptide sequence modulates the redox properties of a whole enzyme
      family.
AB  - BACKGROUND: Disulfide exchange reactions are catalyzed by thiol/disulfide
      oxidoreductases. These enzymes possess a thioredoxin fold and contain a catalytic
      disulfide with the sequence Cys-X-X-Cys at the N terminus of an alpha helix.
      Despite these similarities, the various members differ strongly in their redox
      potentials (-122 mV to -270 mV). Using the strong oxidant DsbA from Escherichia
      coli as a model system, we investigated whether the redox properties of these
      enzymes can be modulated rationally by exchange of the X-X dipeptide. RESULTS:
      The X-X dipeptide of DsbA (Cys30-Pro31-His32-Cys33) was exchanged by the
      dipeptides of eukaryotic protein disulfide isomerase (PDI; Gly-His), glutaredoxin
      (Pro-Tyr), and thioredoxin (Gly-Pro) from E. coli. All variants were less
      oxidizing than wild-type DsbA and their redox potentials were in the order of the
      related natural enzymes (DsbA > PDI > glutaredoxin > thioredoxin). The
      equilibrium constant between glutathione and the thioredoxin-like variant
      increased 1200-fold compared with wild-type DsbA. The variants also showed a
      strong increase in the pKa of the nucleophilic cysteine (Cys30). As for
      glutaredoxin and thioredoxin, the catalytic disulfide stabilized the
      corresponding variants while destabilizing wild-type DsbA and the PDI-like
      variant. CONCLUSIONS: The X-X dipeptide in the active site of thiol/disulfide
      oxidoreductases appears to be the main determinant of the redox properties of
      these enzymes. This empirical finding should be very useful for the design of new
      thiol/disulfide oxidoreductases with altered redox potentials and for studying
      the function of these enzymes in vivo.

PMID- 9562547
TI  - A protein engineering analysis of the transition state for protein folding:
      simulation in the lattice model.
AB  - BACKGROUND: Protein engineering has been used extensively to evaluate the
      properties of transition states in protein folding. Although the method has
      proved useful, its limitations and the details of interpretation of the obtained
      results remain largely unexplored. RESULTS: Lattice model simulations are used to
      test and verify the protein engineering analysis of the transition state in
      protein folding. It is shown that in some cases - but not always - this method is
      able to determine the transition state with reasonable accuracy. Limitations of
      protein engineering are revealed and analyzed. In particular, the change in non
      native interactions as a result of mutations is shown to influence the results of
      the protein engineering analysis. Furthermore, the temperature dependencies of
      phi values (which are a measure of the participation of a residue in the
      transition state) and the character of the transition state ensemble are studied.
      It is shown that as a general trend phi values decrease when the temperature
      decreases, a finding consistent with recent experimental results. Our analysis
      suggests that this trend results primarily from the formation of some contacts
      (native and non-native) in the unfolded state at a lower temperature, when the
      barrier for folding is energetic. CONCLUSIONS: Our analysis helps to interpret
      the results of protein engineering and allows observed &phi; values to be
      directly related to structural features of the unfolded state, the transition
      state and the native state.

PMID- 9562548
TI  - Computational analysis of thermal stability: effect of Ile-->Val mutations in
      human lysozyme.
AB  - BACKGROUND: Free energy calculations are carried out to study the change of
      thermal stability caused by Ile23-->Val, Ile56-->Val, Ile89-->Val and Ile106-
      >Val mutations in human lysozyme. In order to examine the dependence of the free
      energy difference, DeltaDeltaG, on the denatured-state structure, extended and
      native-like conformations are employed as initial conformations in the denatured
      state simulations. RESULTS: Calculated values of DeltaDeltaG for the mutations,
      Ile56-->Val, Ile89-->Val and Ile106-->Val, were in good agreement with
      experimental values when the native-like structure was employed in the respective
      denatured-state simulations. In the case of Ile23-->Val, a considerable
      difference between the calculated and experimental values of DeltaDeltaG was
      observed. CONCLUSIONS: The physical nature of Ile56-->Val, Ile89-->Val and Ile106
      ->Val mutations was rationally characterized by a free energy component analysis.
      It is suggested that the alpha domain in which Ile23 is included is considerably
      structured even in the denatured state.

PMID- 9562549
TI  - Chain-like conformation of heat-denatured ribonuclease A and cytochrome c as
      evidenced by solution X-ray scattering.
AB  - BACKGROUND: Although the characterization of heat-denatured proteins is essential
      for understanding the thermodynamic mechanism of protein folding, their
      structural features are still unclear and controversial. In order to address this
      problem, we studied the size and shape of the heat-denatured states of bovine
      ribonuclease A (RNase A) and horse ferricytochrome c (cytochrome c) by solution X
      ray scattering. RESULTS: RNase A has four disulfide bonds, whereas cytochrome c,
      with a covalently bound heme group, has no disulfide bond. Guinier plots show
      that the heat-denatured RNase A is relatively compact, but the heat-denatured
      cytochrome c is expanded. On the other hand, the Kratky plots of the two proteins
      are similar, indicating that the heat-denatured proteins assume a chain-like
      disordered conformation. The X-ray scattering of RNase A and cytochrome c at
      various temperatures confirmed that their thermal transitions from a globular
      native state to a chain-like extended conformation can be approximated well by a
      two-state transition. CONCLUSIONS: These results indicate that the heat-denatured
      RNase A and cytochrome c are substantially unfolded according to the criteria of
      solution X-ray scattering, although the heat-denatured RNase A remains compact
      because of the presence of the disulfide bonds. The results also confirm that the
      thermal denaturation occurs cooperatively with the breakdown of secondary and
      tertiary structure.

PMID- 9562550
TI  - Models of protein interactions: how to choose one.
AB  - BACKGROUND: There have been many attempts to approximate realistic protein
      interaction energies by coarse graining (i.e. considering interactions between
      amino acids rather than those between atoms). In particular, many 20-letter
      models have been derived (corresponding to the 20 naturally occurring amino
      acids). Because such models remain computationally infeasible, many two-letter
      models have been proposed as further simplifications. The choice of which model
      to use remains arbitrary, however. In this work, we formulate the framework
      within which the quality of approximate interaction potentials with respect to
      folding can be defined explicitly. RESULTS: Using a recently proposed criterion
      for comparing interaction matrices, we compare various 20 x 20 interaction
      matrices and obtain the two-letter model that most closely approximates each 20 x
      20 matrix. We find that there are considerable differences among the 20 x 20
      matrices. In particular, some matrices are much more similar to the hydrophobic
      model than others. Furthermore, we find that although the best two-letter
      approximation of a 20-letter model is a significantly better approximation than a
      random two-letter model, it is still a poor approximation of realistic protein
      interactions. CONCLUSIONS: The determination of the best two-letter
      approximations of various 20-letter models of protein interaction energies
      reveals the degree to which hydrophobic interactions dominate in each of the
      models and hence in proteins.

PMID- 9562551
TI  - Initial hydrophobic collapse is not necessary for folding RNase A.
AB  - BACKGROUND: One of the main distinctions between different theories describing
      protein folding is the predicted sequence of secondary structure formation and
      compaction during the folding process. Whether secondary structure formation
      precedes compaction of the protein molecules or secondary structure formation is
      driven by a hydrophobic collapse cannot be decided unequivocally on the basis of
      existing experimental data. RESULTS: In this study, we investigate the refolding
      of chemically denatured, disulfide-intact ribonuclease A (RNase A) by monitoring
      compaction and secondary structure formation using stopped-flow dynamic light
      scattering and stopped-flow CD, respectively. Our data reveal the formation of a
      considerable amount of secondary structure early in the refolding of the slow
      folding species of RNase A without a significant compaction of the molecules. A
      simultaneous formation of secondary structure and compaction is observed in the
      subsequent rate-limiting step of folding. CONCLUSIONS: During folding of RNase A
      an initial global hydrophobicity is not observed, which contradicts the view that
      this is a general requirement for protein folding. This folding behavior could be
      typical of similar, moderately hydrophobic proteins.

PMID- 9562552
TI  - Protein design: a perspective from simple tractable models 
AB  - Recent progress in computational approaches to protein design builds on advances
      in statistical mechanical protein folding theory. Here, the number of sequences
      folding into a given conformation is evaluated and a simple condition for a
      protein model's designability is outlined.

PMID- 9562553
TI  - Morphology of protein-protein interfaces.
AB  - BACKGROUND: Most soluble proteins are active as low-number oligomers. Statistical
      surveys of oligomeric proteins have defined the roles of hydrophobicity and
      complementarity in the stability of protein interfaces, but tend to average
      structural features over a diverse set of protein-protein interfaces, blurring
      information on how individual interfaces are stabilized. RESULTS: We report a
      visual survey of 136 homodimeric proteins from the Brookhaven Protein Data Bank,
      with images that highlight the major structural features of each protein-protein
      interaction surface. Nearly all of these proteins have interfaces formed between
      two globular subunits. Surprisingly, the pattern of hydrophilicity over the
      surface of these interfaces is quite variable. Approximately one-third of the
      interfaces show a recognizable hydrophobic core, with a single large, contiguous,
      hydrophobic patch surrounded by a ring of intersubunit polar interactions. The
      remaining two-thirds of the proteins show a varied mixture of small hydrophobic
      patches, polar interactions and water molecules scattered over the entire
      interfacial area. Ten proteins in the survey have intertwined interfaces formed
      by extensive interdigitation of the two subunit chains. These interfaces are very
      hydrophobic and are associated with proteins that require both stability and
      internal symmetry. CONCLUSIONS: The archetypal protein interface, with a defined
      hydrophobic core, is present in only a minority of the surveyed homodimeric
      proteins. Most homodimeric proteins are stabilized by a combination of small
      hydrophobic patches, polar interactions and a considerable number of bridging
      water molecules. The presence or absence of a hydrophobic core within these
      interfaces does not correlate with specific protein functions.

PMID- 9562554
TI  - Conformational variability of the N-terminal helix in the structure of ribosomal
      protein S15.
AB  - BACKGROUND: Ribosomal protein S15 is a primary RNA-binding protein that binds to
      the central domain of 16S rRNA. S15 also regulates its own synthesis by binding
      to its own mRNA. The binding sites for S15 on both mRNA and rRNA have been
      narrowed down to less than a hundred nucleotides each, making the protein an
      attractive candidate for the study of protein-RNA interactions. RESULTS: The
      crystal structure of S15 from Bacillus stearothermophilus has been solved to 2.1
      A resolution. The structure consists of four alpha helices. Three of these
      helices form the core of the protein, while the N-terminal helix protrudes out
      from the body of the molecule to make contacts with a neighboring molecule in the
      crystal lattice. S15 contains a large conserved patch of basic residues which
      could provide a site for binding 16S rRNA. CONCLUSIONS: The conformation of the N
      terminal alpha helix is quite different from that reported in a recent NMR
      structure of S15 from Thermus thermophilus. The intermolecular contacts that this
      alpha helix makes with a neighboring molecule in the crystal, however, closely
      resemble the intramolecular contacts that occur in the NMR structure. This
      conformational variability of the N-terminal helix has implications for the range
      of possible S15-RNA interactions. A large, conserved basic patch at one end of
      S15 and a cluster of conserved but exposed aromatic residues at the other end
      provide two possible RNA-binding sites on S15.

PMID- 9562555
TI  - High-resolution structures of variant Zif268-DNA complexes: implications for
      understanding zinc finger-DNA recognition.
AB  - BACKGROUND: Zinc fingers of the Cys2-His2 class comprise one of the largest
      families of eukaryotic DNA-binding motifs and recognize a diverse set of DNA
      sequences. These proteins have a relatively simple modular structure and key base
      contacts are typically made by a few residues from each finger. These features
      make the zinc finger motif an attractive system for designing novel DNA-binding
      proteins and for exploring fundamental principles of protein-DNA recognition.
      RESULTS: Here we report the X-ray crystal structures of zinc finger-DNA complexes
      involving three variants of Zif268, with multiple changes in the recognition
      helix of finger one. We describe the structure of each of these three-finger
      peptides bound to its corresponding target site. To help elucidate the
      differential basis for site-specific recognition, the structures of four other
      complexes containing various combinations of these peptides with alternative
      binding sites have also been determined. CONCLUSIONS: The protein-DNA contacts
      observed in these complexes reveal the basis for the specificity demonstrated by
      these Zif268 variants. Many, but not all, of the contacts can be rationalized in
      terms of a recognition code, but the predictive value of such a code is limited.
      The structures illustrate how modest changes in the docking arrangement
      accommodate the new sidechain-base and sidechain-phosphate interactions. Such
      adaptations help explain the versatility of naturally occurring zinc finger
      proteins and their utility in design.

PMID- 9562556
TI  - Structure and control of pyridoxal phosphate dependent allosteric threonine
      deaminase.
AB  - BACKGROUND: Feedback inhibition of biosynthetic threonine deaminase (TD) from
      Escherichia coli provided one of the earliest examples of protein-based metabolic
      regulation. Isoleucine, the pathway end-product, and valine, the product of a
      parallel pathway, serve as allosteric inhibitor and activator, respectively. This
      enzyme is thus a useful model system for studying the structural basis of
      allosteric control mechanisms. RESULTS: We report the crystal structure of TD at
      2.8 A resolution. The tetramer has 222 symmetry, with C-terminal regulatory
      domains projecting out from a core of catalytic PLP-containing N-terminal
      domains. The subunits, and especially the regulatory domains, associate
      extensively to form dimers, which associate less extensively to form the
      tetramer. Within the dimer, each monomer twists approximately 150 degrees around
      a thin neck between the domains to place its catalytic domain adjacent to the
      regulatory domain of the other subunit. CONCLUSIONS: The structure of TD and its
      comparison with related structures and other data lead to the tentative
      identification of the regulatory binding site and revealed several implications
      for the allosteric mechanism. This work prepares the way for detailed
      structure/function studies of the complex allosteric behaviour of this enzyme.

PMID- 9562557
TI  - EF-hands at atomic resolution: the structure of human psoriasin (S100A7) solved
      by MAD phasing.
AB  - BACKGROUND: The S100 family consists of small acidic proteins, belonging to the
      EF-hand class of calcium-binding proteins. They are primarily regulatory
      proteins, involved in cell growth, cell structure regulation and signal
      transduction. Psoriasin (S100A7) is an 11.7 kDa protein that is highly
      upregulated in the epidermis of patients suffering from the chronic skin disease
      psoriasis. Although its exact function is not known, psoriasin is believed to
      participate in the biochemical response which follows transient changes in the
      cellular Ca2+ concentration. RESULTS: The three-dimensional structure of holmium
      substituted psoriasin has been determined by multiple anomalous wavelength
      dispersion (MAD) phasing and refined to atomic resolution (1.05 A). The structure
      represents the most accurately determined structure of a calcium-binding protein.
      Although the overall structure of psoriasin is similar to those of other S100
      proteins, several important differences exist, mainly in the N-terminal EF-hand
      motif that contains a distorted loop and lacks a crucial calcium-binding residue.
      It is these minor differences that may account for the different specificities
      among members of this family. CONCLUSIONS: The structure of human psoriasin
      reveals that this protein, in contrast to other S100 proteins with known
      structure, is not likely to strongly bind more than one calcium ion per monomer.
      The present study contradicts the idea that calcium binding induces large changes
      in conformation, as suggested by previously determined structures of apo forms of
      S100 proteins. The substitution of Ca2+ ions in EF-hands by lanthanide ions may
      provide a general vehicle for structure determination of S100 proteins by means
      of MAD phasing.

PMID- 9562558
TI  - Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the
      winged helix-turn-helix family.
AB  - BACKGROUND: The transcription of interferon (IFN) and IFN-inducible genes is
      mainly regulated by the interferon regulatory factor (IRF) family of proteins,
      which recognize a unique AAGTGA hexamer repeat motif in the regulatory region of
      IFN genes. A DNA-binding domain of approximately 100 amino acids has been
      commonly found in the IRF family of proteins, but it has no sequence homology to
      known DNA-binding motifs. Elucidation of the structures of members of the IRF
      family is therefore useful to the understanding of the regulation and evolution
      of the immune system at the structural level. RESULTS: The solution structure of
      the DNA-binding domain of interferon regulatory factor-2 (IRF-2) has been
      determined by NMR spectroscopy. It is composed of a four-stranded antiparallel
      beta sheet and three alpha helices, and its global fold is similar to those of
      the winged helix-turn-helix (wHTH) family of proteins. A long loop (Pro37-Asp51)
      is found immediately before the HTH motif, which is not found in other wHTH
      proteins. The NMR signals of residues in this long loop, as well as the second
      helix of the HTH motif, are strongly affected upon the addition of the hexamer
      repeat DNA, suggesting that these structural elements participate in DNA
      recognition and binding. CONCLUSIONS: The structural similarity of the DNA
      binding domain of IRF-2 with those of proteins in the wHTH family shows that the
      IRF proteins belong to the wHTH family, even though there is no apparent sequence
      homology among proteins of the two families. The sequential structure alignment
      program (SSAP) shows that IRF-2 has a slightly different structure from typical
      wHTH proteins, mainly in the orientation of helix 2. The IRF family of proteins
      should therefore be categorized into a subfamily of the wHTH family. The evidence
      here implies that the evolutional pathway of the IRF family is distinct from that
      of the other wHTH proteins, in other words, the immune system diverged from an
      evolutional stem at an early stage.

PMID- 9562559
TI  - Three-dimensional reconstructions from cryoelectron microscopy images reveal an
      intimate complex between helicase DnaB and its loading partner DnaC.
AB  - BACKGROUND: DNA helicases play a fundamental role in all aspects of nucleic acid
      metabolism and defects in these enzymes have been implicated in a number of
      inherited human disorders. DnaB is the major replicative DNA helicase in
      Escherichia coli and has been used as a model system for studying the structure
      and function of hexameric helicases. The native protein is a hexamer of identical
      subunits, which in solution forms a complex with six molecules of the loading
      protein DnaC. DnaB is delivered from this complex onto the DNA template, with the
      subsequent release of DnaC. We report here the structures of the DnaB helicase
      hexamer and its complex with DnaC under a defined set of experimental conditions,
      as determined by three-dimensional cryoelectron microscopy. It was hoped that the
      structures would provide insight into the mechanisms of helicase activity.
      RESULTS: The DnaB structure reveals that six DnaB monomers assemble as three
      asymmetric dimers to form a polar, ring-like hexamer. The hexamer has two faces,
      one displaying threefold and the other sixfold symmetry. The six DnaC protomers
      bind tightly to the sixfold face of the DnaB hexamer. This is the first report of
      a three-dimensional structure of a helicase obtained using cryoelectron
      microscopy, and the first report of the structure of a helicase in complex with a
      loading protein. CONCLUSIONS: The structures of the DnaB helicase and its complex
      with DnaC reveal some interesting structural features relevant to helicase
      function and to the assembly of the two-protein complex. The results presented
      here provide a basis for a more complete understanding of the structure and
      function of these important proteins.

PMID- 9562560
TI  - How do kinases transfer phosphoryl groups?
AB  - Understanding how phosphoryl transfer is accomplished by kinases, a ubiquitous
      group of enzymes, is central to many biochemical processes. Qualitative analysis
      of the crystal structures of enzyme-substrate complexes of kinases reveals
      structural features of these enzymes important to phosphoryl transfer. Recently
      determined crystal structures which mimic the transition state complex have added
      new insight into the debate as to whether kinases use associative or dissociative
      mechanisms of catalysis.

PMID- 9562561
TI  - Structure of a microbial homologue of mammalian platelet-activating factor
      acetylhydrolases: Streptomyces exfoliatus lipase at 1.9 A resolution.
AB  - BACKGROUND: Neutral lipases are ubiquitous and diverse enzymes. The molecular
      architecture of the structurally characterized lipases is similar, often despite
      a lack of detectable homology at the sequence level. Some of the microbial
      lipases are evolutionarily related to physiologically important mammalian
      enzymes. For example, limited sequence similarities were recently noted for the
      Streptomyces exfoliatus lipase (SeL) and two mammalian platelet-activating factor
      acetylhydrolases (PAF-AHs). The determination of the crystal structure of SeL
      allowed us to explore the structure-function relationships in this novel family
      of homologous hydrolases. RESULTS: The crystal structure of SeL was determined by
      multiple isomorphous replacement and refined using data to 1.9 A resolution. The
      molecule exhibits the canonical tertiary fold of an alpha/beta hydrolase. The
      putative nucleophilic residue, Ser131, is located within a nucleophilic elbow and
      is hydrogen bonded to His209, which in turn interacts with Asp177. These three
      residues create a triad that closely resembles the catalytic triads found in the
      active sites of other neutral lipases. The mainchain amides of Met132 and Phe63
      are perfectly positioned to create an oxyanion hole. Unexpectedly, there are no
      secondary structure elements that could render the active site inaccessible to
      solvent, like the lids that are commonly found in neutral lipases. CONCLUSIONS:
      The crystal structure of SeL reinforces the notion that it is a homologue of the
      mammalian PAF-AHs. We have used the catalytic triad in SeL to model the active
      site of the PAF-AHs. Our model is consistent with the site-directed mutagenesis
      studies of plasma PAF-AH, which implicate Ser273, His351 and Asp296 in the active
      site. Our study therefore provides direct support for the hypothesis that the
      plasma and isoform II PAF-AHs are triad-containing alpha/beta hydrolases.

PMID- 9562562
TI  - The crystal structure of an intramolecular trans-sialidase with a NeuAc alpha2-
      >3Gal specificity.
AB  - BACKGROUND: Intramolecular trans-sialidase from leech (Macrobdella decora) is a
      unique enzyme which cleaves the terminal neuraminic acid (NeuAc) residue from
      sialoglycoconjugates, releasing 2, 7-anhydro-neuraminic acid (2,7-anhydro-NeuAc).
      It is the first enzyme found to exhibit strictly specific cleavage of NeuAc
      alpha2-->3Gal linkages in sialoglycoconjugates. The release of 2,7-anhydro-NeuAc
      instead of NeuAc implies a unique mechanism, in which the sialosyl linkage is
      transferred within the sialoglycoconjugate rather than hydrolyzed. The aims of
      the structural study were to gain structural insight into the strict specificity
      and unique mechanism of this unusual enzyme. RESULTS: . The 2.0 A crystal
      structure of recombinant leech intramolecular trans-sialidase has been solved by
      multiple isomorphous replacement. The 1.8 A structure of the enzyme in complex
      with 2-deoxy-2, 3-didehydro-NeuAc was also solved. The refined model comprising
      residues 81-769 has a catalytic beta-propeller domain (C), a N-terminal lectin
      like domain (II) and an irregular beta-stranded domain (III) inserted into the
      catalytic domain. The structure reveals several possible carbohydrate-binding
      features: domain II has a concave face, like that of other sialidases, and there
      is a suitable surface charge distribution at the domain III-C interface.
      CONCLUSIONS: Structural comparisons showed closer evolutionary relationships to
      bacterial sialidases than to viral neuraminidases. Mainchain and sidechain atoms
      around Thr593 make the glycerol-binding pocket incapable of accommodating an
      extended equatorial 6-glycerol group, implying that the 6-glycerol group of the
      reaction intermediate may occupy an axial position, which is also required by the
      catalytic mechanism. The steric hindrance introduced by the bulky sidechain of
      Trp734 above the 2-carboxylate group may explain the lack of water involvement in
      the cleavage reaction and the substrate specificity.

PMID- 9562564
TI  - Gs alpha meets its target--shedding light on a key signal transduction event.
AB  - The recently determined crystal structure of Gs alpha bound to a catalytically
      active form of adenylyl cyclase reveals the location of the enzyme's active site
      and provides the first view of heterotrimeric G protein alpha subunit activating
      a downstream effector. Comparison with the structure of a catalytically inactive
      form of adenylyl cyclase suggests a plausible allosteric mechanism whereby the
      synergistic activators Gs alpha and forskolin stimulate the activity of adenylyl
      cyclase.

PMID- 9562563
TI  - How glutaminyl-tRNA synthetase selects glutamine.
AB  - BACKGROUND: Aminoacyl-tRNA synthetases covalently link a specific amino acid to
      the correct tRNA. The fidelity of this reaction is essential for accurate protein
      synthesis. Each synthetase has a specific molecular mechanism to distinguish the
      correct pair of substrates from the pool of amino acids and isologous tRNA
      molecules. In the case of glutaminyl-tRNA synthetase (GlnRS) the prior binding of
      tRNA is required for activation of glutamine by ATP. A complete understanding of
      amino acid specificity in GlnRS requires the determination of the structure of
      the synthetase with both tRNA and substrates bound. RESULTS: A stable glutaminly
      adenylate analog, which inhibits GlnRS with a Ki of 1.32 microM, was synthesized
      and cocrystallized with GlnRS and tRNA2Gln. The crystal structure of this ternary
      complex has been refined at 2.4 A resolution and shows the interactions made
      between glutamine and its binding site. CONCLUSIONS: To select against glutamic
      acid or glutamate, both hydrogen atoms of the nitrogen of the glutamine sidechain
      are recognized. The hydroxyl group of Tyr211 and a water molecule are responsible
      for this recognition; both are obligate hydrogen-bond acceptors due to a network
      of interacting sidechains and water molecules. The prior binding of tRNAGln that
      is required for amino acid activation may result from the terminal nucleotide,
      A76, packing against and orienting Tyr211, which forms part of the amino acid
      binding site.

PMID- 9562567
TI  - Vascular permeability factor/vascular endothelial growth factor and vascular
      stroma formation in neoplasia. Insights from in situ hybridization studies.
AB  - The formation of vascular stroma plays an important role in the pathophysiology
      of malignancy. We describe the use of in situ hybridization in our laboratory as
      a tool to study the role of vascular permeability factor/vascular endothelial
      growth factor in the angiogenesis associated with malignancy.

PMID- 9562566
TI  - Earliest steps in primary tumor formation and micrometastasis resolved with
      histochemical markers of gene-tagged tumor cells.
AB  - To facilitate detection of tumor cells at the highest resolution in any organ in
      athymic nude mouse model systems, a histochemical marker gene [bacterial lacZ or
      human placental alkaline phosphatase (ALP)] was transfected into specified
      transformed/tumor cells (fibrosarcoma or neuroblastoma). The fates of tumor cells
      were followed qualitatively and quantitatively by histochemical staining of whole
      organs or organ sections. Primary tumors developed initially via formation of
      "curly-haired" complexes of cells in the subcutis or dermis, followed by division
      of a large fraction of cells. When two tumor classes were mixed before injection,
      outgrowth occurred in regional concentrations of the primary tumor. Blood
      microvessels were detectable within 72 hr of injection, growing into tumor
      regions. iv injection routinely yielded multicellular foci in the lungs within
      minutes as precursors of experimental metastases. Micrometastasis was further
      resolved with cells "inactivated" by different treatments and by co-injection of
      two different tagged cell types. These approaches using different histochemical
      marker genes to "tag" different tumor cell classes, along with more advanced
      molecular biological approaches, permit us to characterize gene expression and
      its reversibility during the earliest stages of primary tumor formation and
      micrometastasis to virtually any organ in the recipient animal.

PMID- 9562568
TI  - Preferential activation of the epidermal growth factor receptor in human colon
      carcinoma liver metastases in nude mice.
AB  - Increased epidermal growth factor receptor (EGF-R) gene expression and functional
      protein levels correlate with the metastatic potential of human colon carcinoma
      (HCC) cells in nude mice. The purpose of this study was to determine whether the
      production of liver metastases by HCC cells depends on the EGF-R activation
      status and whether different organ microenvironments influence this activation.
      Using two independent monoclonal antibodies specific for the activated (i.e.,
      tyrosine-phosphorylated) EGF-R, increased immunoreactivity was observed in HCC
      cells growing as metastatic lesions in the livers of athymic nude mice. Staining
      was observed throughout these lesions, both peripherally and centrally. In
      contrast, little or no immunoreactivity for activated EGF-R was observed in
      primary tumors growing orthotopically in the cecum or ectopically in the subcutis
      of nude mice. Immunohistochemistry for total EGF-R levels (irrelevant of
      activation status) demonstrated similar levels of immunoreactivity in HCC tumors
      growing in the cecum, subcutis, or liver of nude mice, indicating that total EGF
      R levels are not altered after growth in these different microenvironments.
      Controls included immunohistochemistry for total and activated EGF-R levels in
      HCC cells growing in vitro under serum-free or EGF-stimulated conditions and A431
      epidermoid carcinoma growing in nude mice. Western blot analyses confirmed the
      specificity of the antibodies for the activated EGF-R. These results suggest that
      the production of liver metastasis by HCC cells depends in part on the response
      of tumor cells to organ-derived growth factors and hence the activation of
      specific cell surface tyrosine kinase receptors.

PMID- 9562569
TI  - Endogenous IL-2 in cancer cells: a marker of cellular proliferation.
AB  - We have previously demonstrated that interleukin-2 (IL-2) receptors, IL-2
      protein, and mRNA for IL-2 are present in human carcinomas in vitro and in vivo.
      Carcinoma cells synchronized in the G2/M-phase of the cell cycle express
      significantly more intracytoplasmic IL-2 as well as IL-2R-beta and -gamma than
      tumor cells in the G0/G1-phase. Here we evaluated immunohistologically the cell
      cycle-dependent distribution of the proliferation-associated Ki-67 antigen and
      expression of the cytokine IL-2 in four different carcinoma cell lines. In
      addition, 34 tissue samples from patients with squamous cell carcinomas of the
      head and neck were simultaneously analyzed for Ki-67 and IL-2 expression and the
      data were correlated to the histological grade of the tumors. All tumor cell
      lines were shown to express IL-2 in the Golgi complex. The strongest IL-2
      expression was seen in tumor cells undergoing mitosis, identified by double
      staining with the antibody to Ki-67. In the tumor tissue, the highest level of co
      expression of IL-2 and Ki-67 was observed in poorly differentiated carcinomas,
      with a labeling index (LI) of 67. 2% for IL-2 and 68.8% for Ki-67. Well
      differentiated carcinomas showed a significantly lower expression of both
      proteins (LI 35.0% for IL-2 and 26.5% for Ki-67). The correlation between the
      labeling indices was statistically significant (r = 0.747; p<0.001). These
      results demonstrate that IL-2 expression in human carcinoma tissues is strongly
      associated with cell proliferation and significantly correlates with the
      histological tumor grade.

PMID- 9562570
TI  - Stem cells and rat liver carcinogenesis: contributions of confocal and electron
      microscopy.
AB  - Microscopic analysis in combination with cytochemistry and immunocytochemistry
      has revealed the presence of four cell types not previously described in the
      portal area and parenchyma of the liver from an experimental rodent
      hepatocarcinogenic rat model. Within the intrahepatic bile ductules, which
      proliferate after administration of chemical carcinogens and partial hepatectomy,
      small, undifferentiated nonpolarized, nonepithelial cells with a blast-like
      phenotype and polarized epithelial cells different from the polarized epithelial
      cells that typically line the walls of the bile ductules were found. In the
      connective tissue stroma surrounding the bile ductules, nonpolarized epithelial
      cells with hepatocyte phenotype were found. In the parenchyma, subpopulations of
      bile ductule epithelial cells that established ATPase-positive bile canalicular
      structures, including the formation of desmosomes and tight junctions, with
      parenchymal hepatocytes within the hepatic lobule were found. These observations
      raise the following questions in this model. Are there undifferentiated
      progenitor cells with stem cell-like properties within bile ductules? What are
      the interrelations of the newly described cell types with each other, with
      parenchymal hepatocytes, with preneoplastic nodules, and with hepatomas? Do the
      heterogeneous cell types within the bile ductules, in the surrounding connective
      tissue, and within the hepatic cords represent intermediate stages of single or
      multiple cell lineage pathways leading to hepatocyte differentiation, liver
      regeneration, and/or preneoplastic nodule formation?

PMID- 9562571
TI  - Lectin intravital perfusion studies in tumor-bearing mice: micrometer-resolution,
      wide-area mapping of microvascular labeling, distinguishing efficiently and
      inefficiently perfused microregions in the tumor.
AB  - Intravital lectin perfusion was combined with computer-guided scanning digital
      microscopy to map the perfused elements of the vasculature in tumor-bearing mice.
      High-precision composite images (spatial precision 1.3 micron and optical
      resolution 1.5 micron) were generated to permit exact positioning,
      reconstruction, analysis, and mapping of entire tumor cross-sections (c. 1 cm in
      diameter). Collation of these mosaics with nuclear magnetic resonance maps in the
      same tumor plane identified sites of rapid contrast medium uptake as tumor blood
      vessels. Digitized imaging after intravital double labeling allowed polychromatic
      visualization of two different types of mismatched staining. First, simultaneous
      application of two lectins, each bearing a different fluorochrome, revealed organ
      specific differential processing in the microvascular wall. Second, sequential
      application of two boluses of one lectin, bearing different fluorochromes
      successively, distinguished between double-labeled microvessels, representing
      efficiently perfused vascular segments, and single-labeled microvessels, with
      inefficient or intermittent perfusion. Intravital lectin perfusion images of
      blood vessels in the vital functional state thus highlighted biologically
      significant differences in vessel function and served as high-resolution adjuncts
      to MR imaging.

PMID- 9562572
TI  - An essential role for the interaction between hyaluronan and hyaluronan binding
      proteins during joint development.
AB  - We studied the expression of hyaluronan binding proteins (HABPs) during the
      development of embryonic chick joints, using immunocytochemistry and biotinylated
      HA. The expression of actin capping proteins and of actin itself was also studied
      because the cytoskeleton is important in controlling HA-HABP interactions. Three
      cell surface HABPs were localized in the epiphyseal cartilage, articular
      fibrocartilage, and interzone that comprise the developing joint. Of these three
      HABPs, CD44 was associated with the articular fibrocartilages and interzone,
      whereas RHAMM and the IVd4 epitope were associated with all three tissues.
      Biotinylated HA was localized to interzone and articular fibrocartilages before
      cavity formation and within epiphyseal chondrocytes post cavitation. Actin
      filament bundles were observed at the developing joint line, as was the
      expression of the actin capping protein moesin. Manipulation of joint cavity
      development, using oligosaccharides of HA, disrupted joint formation and was
      associated with decreases in CD44 and actin filament expression as well as
      decreased hyaluronan synthetic capability. These results suggest that HA is
      actively bound by CD44 at the developing joint line and that HA-HABP interactions
      play a major role in the initial separation events occurring during joint
      formation.

PMID- 9562573
TI  - Detection and localization by in situ molecular biology techniques and
      immunohistochemistry of hepatitis C virus in livers of chronically infected
      patients.
AB  - Hepatitis C virus (HCV) detection in the livers of chronically infected patients
      remains a debatable issue. We used immunohistochemistry, in situ hybridization
      (ISH) alone or after microwave heating with FITC-labeled probes, RT-PCR with
      unlabeled primers followed by ISH (RT-PCR-ISH), and in situ RT-PCR with FITC
      labeled primers (in situ RT-PCRd) to localize the virus in 38 liver biopsy
      specimens from 21 chronically infected HCV patients treated with interferon-alpha
      (IFN-alpha). Biopsies were taken at the beginning and end of IFN-alpha treatment
      and 1 year later. Results were compared with that of HCV-PCR in serum. RT-PCR-ISH
      and in situ RT-PCRd showed HCV signal in all liver biopsies even in responders
      with seronegative HCV PCR. This signal was intranuclear, diffuse, or peripheral,
      in hepatocytes, bile ductule cells, and lymphocytes. Cytoplasmic signals were
      occasionally observed. Whereas the percentage of labeled hepatocytes remained
      constant, the number of labeled lymphoid follicles decreased after INF-alpha
      therapy. Immunohistochemistry resulted in the same pattern of positivity but it
      was weaker and inconstant. This study indicates the persistency of HCV latency in
      IFN-alpha responders 1 year after IFN-alpha treatment cessation, a finding that
      certainly deserves confirmation.

PMID- 9562574
TI  - Peptide-amidating enzymes are expressed in the stellate epithelial cells of the
      thymic medulla.
AB  - C-terminal amidation is a post-translational processing step necessary to convey
      biological activity to a large number of regulatory peptides. In this study we
      have demonstrated that the peptidyl-glycine alpha-amidating monooxygenase enzyme
      complex (PAM) responsible for this activity is located in the medullary stellate
      epithelial cells of the thymus and in cultured epithelial cells bearing a
      medullary phenotype, using Northern blot, immunocytochemistry, in situ
      hybridization, and enzyme assays. Immunocytochemical localization revealed a
      granular pattern in the cytoplasm of the stellate cells, which were also positive
      for cytokeratins and a B-lymphocyte-associated antigen. The presence of PAM
      activity in medium conditioned by thymic epithelial cell lines suggests that PAM
      is a secreted product of these cells. Among the four epithelial cell lines
      examined, there was a direct correlation between PAM activity and content of
      oxytocin, an amidated peptide. Taken together, these data provide convincing
      evidence that thymic epithelial cells have the capacity to generate amidated
      peptides that may influence T-cell differentiation and suggest that the amidating
      enzymes could play an important role in the regulation of thymic physiology.

PMID- 9562575
TI  - Acinar cells are target cells for androgens in mouse submandibular glands.
AB  - The variable coding sequence (VCS) multigene family encodes diverse salivary
      proteins, such as the SMR1 prohormone and the PR-VB1 proline-rich protein in the
      rat. In situ hybridization was used to study the cell-specific expression of two
      new mouse VCS genes, Vcs1 and Vcs2. We show that the Vcs1 transcripts, which code
      for a proline-rich protein, MSG1, are highly abundant in male and female parotid
      glands, in which they are specifically detected in acinar cells. No expression
      was seen in the submandibular or sublingual glands. In contrast, Vcs2 transcripts
      were found only in the acinar cells of the submandibular glands (SMGs) of male
      mice, in which they are expressed in response to androgens. Expression was found
      to be heterogeneous within acinar structures. No Vcs2 transcripts were detected
      in the SMGs of females or castrated males by Northern blot, RNase protection, or
      in situ hybridization. Androgen administration to females or castrated males
      induced expression at a level comparable to that of intact males. The Vcs2 gene
      is the first example of a mouse androgen-regulated gene that is expressed in SMG
      acinar cells. This result, in addition to our previous observation on SMR1
      expression in rats, demonstrates that both acinar cells and granular convoluted
      tubule (GCT) cells are target cells for androgen action in rodent SMG.

PMID- 9562576
TI  - Immunocytochemical and In situ hybridization studies of the distribution of
      calbindin D9k in the bovine placenta throughout pregnancy.
AB  - The fetus must transport considerable and increasing amounts of calcium across
      the placental trophoblast epithelium to support growth and development and bone
      formation. Active calcium transport across epithelia has been shown to correlate
      with calbindin D9k or 28k content. This study examined the distribution of
      calbindin D9k (9CBP) protein and mRNA during pregnancy in the bovine placenta to
      determine its possible role in calcium transport in this system. The
      immunocytochemical results show 9CBP in an increasing percentage of
      interplacentomal uninucleate trophoblast cells until, at term, all show a level
      at least eight times that of any other placental cell. There is a similar,
      although smaller, rise in their 9CBP mRNA content. The mature interplacentomal
      binucleate cell ( approximately 5% of the total) contains no 9CBP at any stage of
      pregnancy. In interplacentomal uterine epithelium, 9CBP protein and mRNA decrease
      to zero in late pregnancy but the glands maintain constant low levels throughout.
      In the placentome trophoblast, uninucleate cells show insignificant amounts but
      binucleate cells (15-20% of the total trophoblast cells) contain considerable
      levels of both 9CBP protein and mRNA, as do all the uninucleate uterine
      epithelial cells. The placentomal binucleate cells show peak values at mid
      pregnancy; the placentomal uterine epithelium shows only small changes in levels
      in the second half of pregnancy. Increase in fetal calcium demand in the second
      half of pregnancy therefore correlates with a major increase in 9CBP only in the
      interplacentomal trophoblast, as we have also shown in the sheep and goat,
      indicating an important role for this region in active calcium transport by the
      ruminant placenta. The 9CBP is distributed uniformly in the cytosol and
      nucleoplasm, supporting a role in facilitated diffusion of calcium through the
      cell rather than a vesicular shuttle system.

PMID- 9562578
TI  - Mutations in the gene for cardiac myosin-binding protein C and late-onset
      familial hypertrophic cardiomyopathy.
AB  - BACKGROUND: Mutations in the gene for cardiac myosin-binding protein C account
      for approximately 15 percent of cases of familial hypertrophic cardiomyopathy.
      The spectrum of disease-causing mutations and the associated clinical features of
      these gene defects are unknown. METHODS: DNA sequences encoding cardiac myosin
      binding protein C were determined in unrelated patients with familial
      hypertrophic cardiomyopathy. Mutations were found in 16 probands, who had 574
      family members at risk of inheriting these defects. The genotypes of these family
      members were determined, and the clinical status of 212 family members with
      mutations in the gene for cardiac myosin-binding protein C was assessed. RESULTS:
      Twelve novel mutations were identified in probands from 16 families. Four were
      missense mutations; eight defects (insertions, deletions, and splice mutations)
      were predicted to truncate cardiac myosin-binding protein C. The clinical
      expression of either missense or truncation mutations was similar to that
      observed for other genetic causes of hypertrophic cardiomyopathy, but the age at
      onset of the disease differed markedly. Only 58 percent of adults under the age
      of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68
      of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete
      through the age of 60 years. Survival was generally better than that observed
      among patients with hypertrophic cardiomyopathy caused by other mutations in the
      genes for sarcomere proteins. Most deaths due to cardiac causes in these families
      occurred suddenly. CONCLUSIONS: The clinical expression of mutations in the gene
      for cardiac myosin-binding protein C is often delayed until middle age or old
      age. Delayed expression of cardiac hypertrophy and a favorable clinical course
      may hinder recognition of the heritable nature of mutations in the cardiac myosin
      binding protein C gene. Clinical screening in adult life may be warranted for
      members of families characterized by hypertrophic cardiomyopathy.

PMID- 9562577
TI  - Early pregnancy termination with mifepristone and misoprostol in the United
      States.
AB  - BACKGROUND: Mifepristone and a prostaglandin have been used successfully to
      terminate pregnancy in Europe and China. We report the results of a large U.S.
      study of mifepristone and misoprostol in women with pregnancies of up to nine
      weeks' duration. METHODS: We administered 600 mg of mifepristone and then 400
      microg of misoprostol two days later to 2121 women seeking termination of their
      pregnancies at 17 centers. The women were observed for four hours after the
      administration of misoprostol and returned on day 15 for final assessment.
      RESULTS: Two thousand fifteen women completed the final assessment. Among them,
      pregnancy was terminated in 762 of the 827 women pregnant for < or =49 days (92
      percent), 563 of the 678 women pregnant for 50 to 56 days (83 percent), and 395
      of the 510 women pregnant for 57 to 63 days (77 percent) (P<0.001). Termination
      occurred within 4 hours after the administration of misoprostol in 49 percent of
      the women and within 24 hours in 75 percent. Failures, defined as cases requiring
      surgical intervention for medical reasons or because the patient requested it,
      the abortion was incomplete, or the pregnancy was ongoing, increased with
      increasing duration of pregnancy. The largest increase was in failures
      representing ongoing pregnancy, which increased from 1 percent in the < or =49
      days group to 9 percent in the 57-to-63-days group (P<0.001). Abdominal pain,
      nausea, vomiting, diarrhea, and vaginal bleeding also increased with advancing
      gestational age. Two percent of the women in the < or =49-days group, as compared
      with 4 percent in each of the other two groups, were hospitalized, underwent
      surgical interventions, and received intravenous fluids (P=0.008). CONCLUSIONS:
      This mifepristone-misoprostol regimen is effective in terminating pregnancies,
      especially in women with pregnancies of 49 days' duration or less.

PMID- 9562579
TI  - Genetic defects and clinical characteristics of patients with a form of
      oculocutaneous albinism (Hermansky-Pudlak syndrome).
AB  - BACKGROUND: Hermansky-Pudlak syndrome is characterized by oculocutaneous
      albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid
      lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some
      cases. All identified affected patients in northwest Puerto Rico are homozygous
      for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared
      the clinical and laboratory characteristics of these patients with those of
      patients without the 16-bp duplication. METHODS: Forty-nine patients -- 27 Puerto
      Ricans and 22 patients from the mainland United States who were not of Puerto
      Rican descent -- were given a diagnosis on the basis of albinism and the absence
      of platelet dense bodies. We used the polymerase chain reaction to determine
      which patients carried the 16-bp duplication. RESULTS: Twenty-five of the Puerto
      Rican patients were homozygous for the 16-bp duplication, whereas none of the non
      Puerto Rican patients carried this mutation. Like the patients without the
      duplication, the patients with the 16-bp duplication had a broad variation in
      pigmentation. Nine of 16 adults with the duplication, but none of the 10 without
      it, had a diffusing capacity for carbon monoxide that was less than 80 percent of
      the predicted value. High-resolution computed tomography in 12 patients with the
      16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe
      fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients
      without the duplication revealed minimal fibrosis in three and no fibrosis in the
      rest. Inflammatory bowel disease developed in eight patients (four in each group)
      between 3 and 25 years of age. CONCLUSIONS: The 16-bp duplication in exon 15 of
      HPS, which we found only in Puerto Rican patients, is associated with a broad
      range of pigmentation and an increased risk of restrictive lung disease in
      adults.

PMID- 9562582
TI  - Images in clinical medicine. Echocardiographic detection of a renal-cell
      carcinoma.

PMID- 9562581
TI  - Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in
      metastatic renal-cell carcinoma. Groupe Francais d'Immunotherapie.
AB  - BACKGROUND: Recombinant human interleukin-2 (aldesleukin) and recombinant human
      interferon alfa can induce notable tumor regression in a limited number of
      patients with metastatic renal-cell carcinoma. We conducted a multicenter,
      randomized trial to determine the effect of each cytokine independently and in
      combination, and to identify patients who are best suited for this treatment.
      METHODS: Four hundred twenty-five patients with metastatic renal-cell carcinoma
      were randomly assigned to receive either a continuous intravenous infusion of
      interleukin-2, subcutaneous injections of interferon alfa-2a, or both. The main
      outcome measure was the response rate; secondary outcomes were the rates of event
      free and overall survival. Predictive factors for response and rapid progression
      were identified by multivariate analysis. RESULTS: Response rates were 6.5
      percent, 7.5 percent, and 18.6 percent (P<0.01) for the groups receiving
      interleukin-2, interferon alfa-2a, and interleukin-2 plus interferon alfa-2a,
      respectively. At one year, the event-free survival rates were 15 percent, 12
      percent, and 20 percent, respectively (P=0.01). There was no significant
      difference in overall survival among the three groups. Toxic effects of therapy
      were more common in patients receiving interleukin-2 than in those receiving
      interferon alfa-2a. Response to treatment was associated with having metastasis
      to a single organ and with receiving the combined treatment. The probability of
      rapid progression of disease was at least 70 percent for patients with at least
      two metastatic sites, liver metastases, and a period of less than one year
      between the diagnosis of the primary tumor and the appearance of metastases.
      CONCLUSIONS: Cytokines are active in a few patients with metastatic renal-cell
      carcinoma. The higher response rate and longer event-free survival obtained with
      a combination of cytokines must be balanced against the toxicity of such
      treatment.

PMID- 9562580
TI  - Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma.
      Canadian Urologic Oncology Group.
AB  - BACKGROUND: Most trials of immunomodulators in metastatic renal-cell carcinoma
      have been uncontrolled and subject to selection bias. The objective of this
      blinded, placebo-controlled study was to compare overall response rates, time to
      disease progression, and survival of patients with metastatic renal-cell
      carcinoma treated with recombinant human interferon gamma-1b or placebo. METHODS:
      Patients with biopsy-proved metastatic renal-cell carcinoma were randomly
      assigned to receive interferon gamma-1b (60 microg per square meter of body
      surface area subcutaneously once weekly) or placebo. The primary tumor had been
      treated by nephrectomy or angioinfarction at least three weeks previously.
      Patients were evaluated for radiologic evidence of progression, and all responses
      were independently reviewed by a committee that was unaware of the treatment.
      RESULTS: A total of 197 patients with metastatic renal-cell carcinoma were
      enrolled at 17 centers in Canada. One hundred eighty-one patients could be
      evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were
      given placebo. The groups were well balanced in terms of prognostic factors. Two
      thirds of all patients had Karnofsky scores of 90 or 100, and more than half had
      two or more metastatic sites. Grade I and II toxicity, mostly chills, fever,
      asthenia, or headaches, was reported in 91 percent and 61 percent, respectively,
      of the patients in the interferon group, as compared with 76 percent and 63
      percent in the placebo group. Life-threatening drug-related events were rare,
      occurring in 1 percent of patients in the interferon group. No significant
      differences between groups were observed in overall response rates, time to
      disease progression, or survival. The overall response rate was 4.4 percent (3.3
      percent complete response and 1.1 percent partial response) in the interferon
      group and 6.6 percent (3.3 percent complete response and 3.3 percent partial
      response) in the placebo group (P=0.54), with a rate of durable complete response
      of 1 percent in both groups. The median time to disease progression was 1.9
      months in both groups (P=0.49), and there was no significant difference in median
      survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52).
      CONCLUSIONS: No difference in outcome was observed in patients with metastatic
      renal-cell carcinoma who were treated with interferon gamma-1b as compared with
      placebo. These results emphasize the necessity of testing the efficacy of
      immunomodulators in randomized studies.

PMID- 9562583
TI  - Images in clinical medicine. Renal-cell carcinoma.

PMID- 9562584
TI  - HIV-protease inhibitors.

PMID- 9562586
TI  - Hypertrophic cardiomyopathy--beyond the sarcomere.

PMID- 9562588
TI  - Medicare policy for future generations--a search for a permanent solution.

PMID- 9562587
TI  - Metastatic renal-cell carcinoma: what causes occasional dramatic regressions?

PMID- 9562589
TI  - Accidental nuclear war--a post-cold war assessment.
AB  - BACKGROUND: In the 1980s, many medical organizations identified the prevention of
      nuclear war as one of the medical profession's most important goals. An
      assessment of the current danger is warranted given the radically changed context
      of the post-Cold War era. METHODS: We reviewed the recent literature on the
      status of nuclear arsenals and the risk of nuclear war. We then estimated the
      likely medical effects of a scenario identified by leading experts as posing a
      serious danger: an accidental launch of nuclear weapons. We assessed possible
      measures to reduce the risk of such an event. RESULTS: U.S. and Russian nuclear
      weapons systems remain on a high-level alert status. This fact, combined with the
      aging of Russian technical systems, has recently increased the risk of an
      accidental nuclear attack. As a conservative estimate, an accidental intermediate
      sized launch of weapons from a single Russian submarine would result in the
      deaths of 6,838,000 persons from firestorms in eight U.S. cities. Millions of
      other people would probably be exposed to potentially lethal radiation from
      fallout. An agreement to remove all nuclear missiles from high-level alert status
      and eliminate the capability of a rapid launch would put an end to this threat.
      CONCLUSIONS: The risk of an accidental nuclear attack has increased in recent
      years, threatening a public health disaster of unprecedented scale. Physicians
      and medical organizations should work actively to help build support for the
      policy changes that would prevent such a disaster.

PMID- 9562590
TI  - Differential diagnosis of nontraumatic intracranial hemorrhage.
AB  - Intracranial hemorrhage is a common initial symptom of intracranial vascular
      malformations. Although CT remains important in the acute setting, MR imaging has
      proved invaluable for diagnosis and characterization of intracranial hemorrhage.
      MR imaging of hemorrhage and the differential diagnosis of nontraumatic
      intracranial hemorrhage is presented in this article.

PMID- 9562591
TI  - Classification of vascular malformations of the central nervous system.
AB  - The ability to systematically and meaningfully classify a disease is in many ways
      a reflection of our overall understanding of it. Over time, nosologic schemes
      applied to any disease typically undergo a characteristic evolution from purely
      descriptive, to pathoanatomic and/or embryologic, to finally biological
      definitions. With the recent developments in further elucidating the
      pathophysiology, histopathology, natural history, and cellular biology of various
      vascular malformations occurring within the central nervous system, it is time to
      derive a more comprehensive and "universal" classification system that integrates
      classic pathoanatomic schemes with a biologically defined scheme previously
      developed for systematic vascular malformations. Such a system is proposed and
      discussed, including detailed review of important subtypes.

PMID- 9562592
TI  - Imaging of angiographically occult cerebral vascular malformations.
AB  - The angiographically occult vascular malformations represent an important cause
      of cerebral pathology. The propensity for significant yet often limited
      symptomatology provides for frequent challenge in clinical management.
      Understanding in diagnostic evaluation of occult vascular lesions is often
      limited by varying application of pathologic diagnosis and classification. This
      article attempts to clarify issues of classification while also discussing
      imaging evaluation and its role in clinical management.

PMID- 9562593
TI  - MR angiography of vascular malformations.
AB  - Magnetic resonance angiography (MRA) plays an important role in the evaluation of
      cerebrovascular disease. This is especially true in the diagnosis and management
      of cerebral vascular malformations. Both time-of-flight and phase contrast MRA
      techniques have proved useful for the imaging of all types of cerebral vascular
      malformations including AVMs, dural fistulas, cavernous malformations, and venous
      angiomas. The role of MRA in the evaluation of these lesions is discussed.

PMID- 9562594
TI  - Basic concepts of functional arteriovenous MR imaging malformations.
AB  - This article reviews the technical features of functional MR imaging. Examples
      are presented demonstrating how MR imaging may be used to identify primary
      cortical regions adjacent to AVMs. Preliminary results suggest that cortical
      functions may undergo translocation when the AVM involves eloquent cortex. This
      finding underscores the importance of cortical mapping prior to surgical
      excision.

PMID- 9562595
TI  - Brain arteriovenous malformations.
AB  - The diagnostic evaluation of a brain arteriovenous malformation requires a
      thorough understanding of the imaging features seen on CT, MR, and conventional
      angiography. Therapeutic planning requires a comprehensive understanding of the
      angioarchitecture of AVMs, necessitation selective and superselective angiography
      in order to give an accurate assessment of the lesion. This article will discuss
      the diagnostic work-up of AVMs. AVM treatment requires a multidisciplinary
      approach that includes interventional neuroradiology, radiosurgery, and
      neurosurgery. The considerations and philosophies of each discipline will
      discussed in order to provide the perspective required for the comprehensive
      treatment of AVMs.

PMID- 9562596
TI  - Endovascular therapy of intracranial arteriovenous malformations. Materials and
      techniques.
AB  - Endovascular therapy can be an integral part of the treatment plan for patients
      with brain AVMs Safe and successful AVM embolization requires familiarity with
      the devices and techniques used and keen awareness of the potential pitfalls and
      complications. This article reviews the technical aspects of endovascular therapy
      of brain AVMs, with reference to specific therapeutic goals.

PMID- 9562597
TI  - Diagnosis and treatment of dural arteriovenous fistulas.
AB  - Dural arteriovenous fistulas (DAVFs) are abnormal vascular connections located
      within the dura mater which are thought to be promoted by venous hypertension and
      venous sinus thrombosis. The symptoms associated with DAVFs depend on the
      direction and adequacy of venous drainage pathways, the amount of arteriovenous
      shunting and specific location of the fistula. Our experience over a period of
      eight years with 268 patients suffering from cranial DAVFs in the transverse,
      sigmoid, superior sagittal, ethmoidal, inferior and superior petrosal, cavernous,
      and marginal sinuses are presented. The clinical presentation, radiographic
      evaluation, and treatment modalities for DAVFs in each of these locations are
      summarized.

PMID- 9562598
TI  - Combined interventional and surgical treatment of arteriovenous malformations.
AB  - This article describes the combined interventional and surgical treatment of
      arteriovenous malformations. The development of embolization as an adjunct to
      microsurgical resection of arteriovenous malformations has expanded the
      therapeutic armamentarium in the treatment of these lesions. Patient selection,
      indications, technical aspects as well as avoidance and treatment of
      complications with regard to endovascular embolization are discussed. Four
      individual cases are presented to show how embolization can be combined with
      microsurgery to achieve optimal treatment results.

PMID- 9562599
TI  - Radiosurgical management of intracranial vascular malformations.
AB  - Stereotactic radiosurgery is an important treatment option for arteriovenous
      malformations (AVMs) and hemorrhagic cavernous malformations. Radiosurgery is
      effective in obliterating AVMs and preventing rebleeding of cavernous
      malformations with two or more hemorrhagic episodes. Outcome analyses of
      radiosurgery for these vascular malformations have provided important information
      to improve the safety and effectiveness of radiosurgical treatment.

PMID- 9562600
TI  - Novel biological response modifiers derived from thalidomide.
AB  - Thalidomide (N-alpha-phthalimidoglutarimide) was used widely as a
      hypnotic/sedative agent in the late 1950s and the early 1960s, but had to be
      withdrawn from the market because of its severe teratogenicity. In spite of this,
      there has been a resurgence of interest in the drug in recent years due to its
      potential usefulness for the treatment of various diseases, including acquired
      immunodeficiency syndrome (AIDS) and graft-versus-host disease (GVHD). The
      effectiveness of the drug in these diseases has been attributed to its specific
      inhibitory activity on tumor necrosis factor-alpha (TNF-alpha) production.
      Because TNF-alpha, a cytokine mediating host defence and immune regulation, with
      a wide range of activities, has deleterious pathophysiological effects in various
      diseases, including AIDS, tumors, rheumatoid arthritis and diabetes, its
      production-regulators are attractive lead compounds for novel biological response
      modifiers. The regulatory effect of thalidomide on TNF-alpha production has been
      found to be bidirectional, depending on both the cell-type and the TNF-alpha
      production-inducer; i.e., thalidomide possesses both enhancing and inhibiting
      activities on TNF-alpha production. Structural modification of thalidomide aiming
      at the creation of superior TNF-alpha production-regulators has afforded a number
      of phenyl- and benzylphthalimide analogs possessing more potent activity than
      thalidomide itself. The structure-activity relationships of these analogs has
      been investigated. The bidirectional TNF-alpha production-regulating activity is
      electronic state- and enantio-dependent, and both pure inhibitors and pure
      enhancers of TNF-alpha production has been obtained. Further structural
      development of the phthalimide analogs has yielded potent non-steroidal androgen
      antagonists.

PMID- 9562601
TI  - Antiproliferative naphthopyrans: biological activity, mechanistic studies and
      therapeutic potential.
AB  - This article will firstly briefly review the newer generation of
      immunosuppressant drugs, focusing mainly on tacrolimus (FK-506), sirolimus
      (rapamycin), mycophenolate mofetil (RS-61443) and leflunomide (HWA 486) and then
      describe work carried out at the Lilly Research Centre on analogues of
      leflunomide and subsequent diversion into a structurally distinct series of
      compounds, the naphthopyrans. A clear structure activity relationship exists
      within this series and selected data from a Concanavalin A stimulated T-cell
      proliferation assay are presented to illustrate this. Although the compounds
      proved to possess little in vivo activity in our rheumatoid arthritis program,
      examination of the compounds in in vitro and in vivo models within the diabetic
      complications group showed the compounds behaved as would be anticipated for
      inhibitors of protein kinase C, although this direct mode of action was clearly
      not correct. Mechanistic investigations revealed that the favoured compound
      290181 blocks phorbol 12,13-dibutyrate-induced binding of transcription factor
      proteins to the PEA3/TRE sequence of the promoter region of the urokinase
      plasminogen activator gene. The compounds also showed antiproliferative effects
      on vascular smooth muscle cells, an in vitro activity that translated into in
      vivo efficacy in a rat model of restenosis. Mechanistic studies here demonstrated
      that 290181 blocks proliferation in the G2/M phase of the cell cycle by binding
      directly to a novel site on tubulin. Finally the compounds were shown to inhibit
      the release of neutral proteases from interleukin-1 stimulated articular
      chondrocytes, this activity having implications in the degenerative aspects of
      osteoarthritis.

PMID- 9562602
TI  - Combinatorial chemistry techniques applied to nonpeptide integrin antagonists.
AB  - The integrins are cell surface receptors that recognize extracellular matrix
      adhesive proteins such as fibrinogen, fibronectin, vitronectin, and VCAM-1
      (vascular cell adhesion molecule-1). Nonpeptide integrin antagonists designed
      after the adhesion recognition sequence RGD (Arg-Gly-Asp) not only have displayed
      efficacy as antithrombotic agents, but also have promise for the treatment of
      cancer and osteoporosis. Combinatorial organic syntheses of chemical mini
      libraries have facilitated nonpeptide lead optimization of integrin antagonists
      with marked success. Although these accomplishments have been realized primarily
      for the discovery of orally active GPIIb/IIIa antagonist antithrombotics,
      vitronectin receptor (avb3) antagonist research has also benefited from such
      rapid synthesis. The purpose of this review is to report progress in
      combinatorial synthesis lead optimization by highlighting the drug design
      strategies and synthetic tactics that have led to improved integrin antagonists.

PMID- 9562603
TI  - Podophyllotoxins: current status and recent developments.
AB  - Podophyllotoxin is a natural product isolated from Podophyllum peltatum and
      Podophyllum emodi and has long been known to possess medicinal properties.
      Etoposide (VP-16), a podophyllotoxin derivative, is currently in clinical use in
      the treatment of many cancers, particularly small cell lung carcinoma and
      testicular cancer. This compound arrests cell growth by inhibiting DNA topo
      isomerase II, which causes double strand breaks in DNA. VP-16 does not inhibit
      tubulin polymerization, however, its parent compound, podophyllotoxin, which has
      no inhibitory activity against DNA topoisomerase II, is a potent inhibitor of
      microtubule assembly. In addition to these two mechanisms of action, an unknown
      third mechanism of action has also been proposed for some of the recent
      modifications of podophyllotoxins. Owing to its severe toxic side effects a
      number of modifications have been done on podophyllotoxin structure. Some of the
      congeners exhibited potent antitumor actiivity, of which etoposide and teniposide
      are in clinical use, NK 611 is in phase II clinical trials and many compounds are
      in the same line. Recent developments on podophyllotoxins have led structure
      activity correlations which have assisted in the design and synthesis of new
      podophyllotoxin derivatives of potential antitumor activity. Modification of the
      A-ring gave compounds having significant activity but less than that of
      etoposide, whereas modification of the B-ring resulted in the loss of activity.
      One of the modifications in the D-ring produced GP-11 which is almost equipotent
      with etoposide. E-ring oxygenation did not affect the DNA cleavage which led to
      the postulation of the third mechanism of action. It has also been observed that
      free rotation of E-ring is necessary for the antitumor activity. The C4
      substituted aglycones have a significant place in these recent developments.
      Epipodophyllotoxin conjugates with DNA cleaving agents such as distamycin
      increased the number of sites of cleavage. The substitution of a glycosidic
      moiety with arylamines produced enhanced activity. Modification in the sugar ring
      resulted in the development of the agent, NK 611 which is in clinical trial at
      present. This article review, the progress of podophyllotoxins from its early
      applications in folk medicine to the most recent modifications and the
      mechanism(s) of action, pharmacology and the structure-activity relationships.

PMID- 9562604
TI  - Organization and expression of basement membrane collagen IV genes and their
      roles in human disorders.
AB  - Six distinct genes have been identified as belonging to the type IV collagen gene
      family. They can be organized into three sets, i.e., COL4A1/COL4A2,
      COL4A3/COL4A4, and COL4A5/COL4A6, which are localized on three different
      chromosomes in humans, 13, 2, and X, respectively. Within each set the genes are
      aligned head-to-head and their expression is regulated by bidirectional promoters
      between the genes. Transcriptional regulation of the COL4A1/COL4A2 set has been
      well characterized. The transcription of COL4A6 seems to be controlled by two
      alternative promoters. While collagen IV molecules composed of alpha1 and alpha2
      chains are broadly distributed, molecules comprising combinations of the other
      four chains, alpha3-alpha6, are important components of specialized basement
      membranes. The precise chain composition of triple-helical molecules assembled
      from the alpha3-alpha6 chains is not entirely clear, but it is hypothesized that
      alpha3-alpha5 chains and alpha5 and alpha6 chains form heterotrimeric molecules.
      Several pieces of evidence indicate that alpha3/alpha4/alpha5 molecules and
      alpha5/alpha6 molecules are components of the basement membrane network. This
      helps explain the observation that the kidney and skin basement membranes from
      patients with Alport syndrome caused by mutations in the alpha5 coding gene,
      COL4A5, are defective in the alpha3, alpha4, and alpha6 chains together with the
      alpha5 chain. Large deletions involving the COL4A5 and COL4A6 genes have been
      found in rare cases of diffuse leiomyomatosis associated with Alport syndrome.

PMID- 9562605
TI  - Nucleotide sugar transporters: elucidation of their molecular identity and its
      implication for future studies.
AB  - Nucleotide sugar transporters are mainly located in the Golgi membranes and carry
      nucleotide sugars, that are produced outside the Golgi apparatus, into the
      organelle, where they serve as substrates for the elongation of carbohydrate
      chains by glycosyltransferases. They are thus indispensable for cellular
      glycoconjugate synthesis and, moreover, may have regulatory roles in producing
      the structural variety of cellular glycoconjugates. Their occurrence has long
      been well recognized, but studies on the molecular bases of their strict
      substrate specificities and modes of action have been hampered by the lack of
      information on their precise molecular structures. Complementary DNAs encoding
      several of these transporters were cloned recently, which represented a
      substantial step forward as to the above mentioned issues. The products of these
      cDNAs are mutually related hydrophobic proteins consisting of 320-400 amino acid
      residues with multiple putative transmembrane helix domains, and are located in
      the Golgi apparatus. This review briefly summarizes the present status of the
      field of nucleotide sugar transporter research, and also presents an outlook of
      the study in this field.

PMID- 9562606
TI  - Identification of a major PAF acetylhydrolase in human serum/plasma as a 43 kDa
      glycoprotein containing about 9 kDa asparagine-conjugated sugar chain(s).
AB  - Platelet-activating factor (PAF) acetylhydrolase from human serum/plasma was
      identified on a polyvinylidene difluoride (PVDF) membrane by electroblotting
      proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). The enzyme activity was detected in the 43 kDa region on the membrane
      as a decrease in the beta-radioluminescence of [3H]acetyl-PAF or by the
      convenient method for determining PAF acetylhydrolase activity (the TCA
      precipitation method). The enzyme activity on treatment with N-glycosidase F
      shifted to the 34 kDa region on the PVDF membrane. On the other hand, only one
      band was observed, corresponding to a molecular mass of 53 kDa, on analysis by
      SDS-PAGE with silver staining. Treatment of the 53 kDa protein with N-glycosidase
      F changed its molecular mass to 43 kDa (protein A). The NH2-terminal 32 amino
      acid sequence of protein A completely corresponds to that of the heterogenous
      enzyme with 54 amino acids deleted from the NH2 terminus reported by Tjoelker et
      al. (Nature 374, 549-553, 1995). Even after trypsin treatment of the N
      glycosidase F-digested enzyme, its PAF-AH activity remained in the 34 kDa region,
      but the contaminating protein A disappeared, on the PVDF membrane. In addition,
      the majority of serum PAF-AH was retained on a Sambucus sieboldiana agglutinin
      (SSA)-agarose column and was eluted with the hapten sugar, lactose. These results
      indicate that PAF acetylhydrolase consisting of a 34 kDa protein and about 9 kDa
      asparagine-conjugated sugar chain(s) is a major enzyme in human serum/plasma.

PMID- 9562607
TI  - Interaction and orientation of an alpha-aminoisobutyric acid- and tryptophan
      containing short helical peptide pore-former in phospholipid vesicles, as
      revealed by fluorescence spectroscopy.
AB  - The interaction and orientation of a membrane protein ion channel model, an alpha
      aminoisobutyric acid analogue of gramicidin B (GBA), in egg yolk
      phosphatidylcholine vesicles was studied by means of fluorescence spectroscopic
      techniques. GBA helices form stable ion-conducting pores in membranes [Jelokhani
      Niaraki et al. (1995) J. Chem. Soc. Perkin Trans. 2, 801-808]. In an alpha
      helical model for the peptide, all Trp residues (intrinsic fluorophores) are
      distributed near the C-terminus. Fluorescence quenching experiments revealed the
      exposure of the helical peptides' C-termini to aqueous environments. Dansyl
      labeled vesicles were used to investigate the GBA dynamism of the interaction
      with membranes. It was shown that considerable amounts of peptide reside on and
      in the vicinity of the outer surface of lipid bilayers. The transmembrane
      transfer to the inner layer is slow due to the high affinity of Trp residues for
      bilayer interfaces which anchor the peptide to the outer surface. A structural
      functional interpretation of the GBA interaction with membranes is presented.

PMID- 9562608
TI  - Interaction of amphotericin B with cholesterol in monolayers, aqueous solutions,
      and phospholipid bilayers.
AB  - The interaction of amphotericin B (AmB) with cholesterol was investigated in
      monolayers, aqueous solutions, and phospholipid vesicles. When AmB was mixed with
      cholesterol, it formed a stable monolayer, implying complex formation in which
      the stoichiometry was primarily 1:1 AmB:cholesterol. However, the interaction of
      AmB with cholesterol in aqueous solutions and lipid vesicles was more complex. In
      aqueous solutions, cholesterol at low concentrations increased the aggregation of
      AmB. But higher concentrations of cholesterol caused dissociation of the
      aggregates of AmB due to the formation of AmB-cholesterol complexes. In lipid
      vesicles, the effect of cholesterol was different from that in aqueous solutions.
      Both in aqueous solutions and lipid vesicles, the overall dissociation of AmB
      molecules occurred on interaction with cholesterol. In addition, the interaction
      of lipid membranes with AmB-cholesterol complexes was investigated by
      differential scanning calorimetry. The incorporation of AmB into lipid bilayers
      led to broadening of the lipid transition and a slight decrease in the transition
      enthalpy, showing that one lipid molecule per AmB molecule was immobilized.
      However, the number of immobilized lipid molecule per AmB molecule increased in
      the coexistence of cholesterol, due to the complex formation between AmB and
      cholesterol.

PMID- 9562609
TI  - Regulation of tissue-type plasminogen activator (tPA) and type-1 plasminogen
      activator inhibitor (PAI-1) gene expression in rat hepatocytes in primary
      culture.
AB  - We have performed a comparative study on tPA and PAI-1 mRNA expression in primary
      cultures of rat hepatocytes and elucidated the possible regulation of these
      factors by certain hormonal stimulation. The tPA mRNA increased 2- to 4-fold in
      the presence of cholera toxin (CT), dibutyryl cyclic AMP (dbcAMP), or 3-isobutyl
      1-methyl xanthine (IBMX), but slightly decreased in the presence of
      dexamethasone. The tPA activity was also changed by these agents in a similar
      fashion. On the contrary, PAI-1 mRNA decreased with CT, dbcAMP, or IBMX, but
      increased transiently with dexamethasone. From results obtained with
      cycloheximide, ongoing protein synthesis was judged to be required for both PAI-1
      induction with dexamethasone and PAI-1 suppression with IBMX, but not for the tPA
      induction with IBMX. Dexamethasone exerted opposite regulatory effects on the tPA
      mRNA expression depending on its concentration: at 10(-8) to 10(-6) M, it
      suppressed the expression; whereas at 10(-10) M, it elevated the expression.

PMID- 9562610
TI  - High glucose-induced abnormal epidermal growth factor signaling.
AB  - We have reported that high glucose conditions (27 mM for 4 days) induces
      activation of protein tyrosine phosphatases (PTPases) which are associated with
      impaired insulin signaling in Rat 1 fibroblasts expressing human insulin
      receptors [Maegawa, H. et al. (1995) J. Biol. Chem. 270, 7724-7730]. In this
      study, we found increased mRNA-levels of a non-receptor type PTPase, protein
      tyrosine phosphatase 1B (PTP1B), and receptor type PTPases, leukocyte common
      antigen-related phosphatase (LAR), and LAR-related phosphatase (LRP), under high
      glucose conditions. In accordance with these results, LAR content was
      significantly increased, whereas LRP content was not increased. Cytosolic PTP1B
      content was increased, but membrane-associated PTP1B content showed no detectable
      change. Pioglitazone, a thiazolidinedione, normalized increased cytosolic PTPase
      activity through reduction of cytosolic PTP1B content, but it had no effect on
      mRNA levels of these PTPases. Under the high glucose condition, we also found
      that epidermal growth factor (EGF)-stimulated signaling, including tyrosine
      phosphorylation of EGF receptor and phosphatidylinositol 3'-kinase activities,
      was attenuated. Nevertheless, pioglitazone failed to restore the attenuated EGF
      signaling. These results indicate that the high glucose conditions cause
      dysfunction of EGF receptor. However, the increased cytosolic PTP1B content is
      not involved in the abnormal regulation of EGF-signaling, in contrast to insulin
      signaling.

PMID- 9562611
TI  - Effects of cis-diamminedichloroplatinum(II) on Escherichia coli and bacteriophage
      systems.
AB  - The effects of cis-diamminedichloroplatinum(II) (cisplatin) on Escherichia coli
      cells and bacteriophages were investigated. The bacteriocidal effect of cisplatin
      was stronger on uvrA or recA mutants than on wild type cells. The drug, like UV,
      induced prophage development in lysogenic bacteria. Host cell reactivation of
      alpha3 replicative form (RF) I DNA treated with cisplatin in vitro was more
      efficient in wild type or recA cells than in uvrA host. When wild type cells were
      exposed to cisplatin, decay of the host's capacity to sustain the viral
      multiplication proceeded nearly in parallel with the loss of colony-forming
      ability, whereas the capacity of uvrA mutant was much more resistant to the drug,
      as compared with the viability. In the DNA preparation from cisplatin-treated
      alpha3-infected wild type cells, RF II was deficient, but the RF I molecules
      extracted from the cells were moderately infective. The microvirid gene A
      protein, required for RF I-->RF II conversion, was hardly detectable in wild type
      cells exposed to cisplatin. The possible relationship between uvr+-dependent
      repair and synthesis of the viral protein is discussed.

PMID- 9562612
TI  - Temperature dependency of thermodynamic parameters in interactions between hen
      egg-white lysozyme (HEL) and anti-HEL antibodies.
AB  - We examined temperature dependency of thermodynamic parameters in the
      interactions between hen egg-white lysozyme (HEL) and anti-HEL antibody, D1.3,
      and two mutant antibodies. The DeltaH degrees values appeared to decrease
      biphasically in the temperature range from 10 to 45 degrees C with the apparent
      inflection point around 30 degrees C. The DeltaG degrees calculated from the KA
      values showed only small differences because of entropy and enthalpy
      compensation. It has been argued that large negative values of heat capacity
      change (DeltaCp degrees), if observed, are mainly derived from hydrophobic
      interactions. However, the observed DeltaCp degrees values were too high to be
      ascribed only to hydrophobic interactions. Moreover, addition of methanol did not
      cause a decrease in the absolute value of DeltaCp degrees.

PMID- 9562613
TI  - Characterization of Fv fragments expressed on phage surface.
AB  - We characterized a phage antibody in which an Fv fragment, namely, a free VH
      fragment noncovalently associated with a VL fragment that is fused with a
      truncated cpIII molecule (VL-DeltacpIII), is expressed on the phage surface. D1.3
      antibody specific for hen egg-white lysozyme was used as a model system. Both VH
      and VL-DeltacpIII fragments were stably expressed and associated with each other
      to form a faithful antigen-binding site. The results of Western blotting
      indicated that more than 5% of phages expressed the Fv fragment on their surface.
      Analysis of the kinetics of binding of the phage antibody to the antigen
      suggested the possibility of presence of phages having multiple-binding sites on
      a single phage particle.

PMID- 9562614
TI  - Effects of point mutations at the flexible loop alanine-145 of Escherichia coli
      dihydrofolate reductase on its stability and function.
AB  - To elucidate the role of a flexible loop (residues 142-149) in the stability and
      function of Escherichia coli dihydrofolate reductase, alanine-145 in this loop
      was substituted by site-directed mutagenesis with ten amino acids (Glu, Phe, Gly,
      His, Ile, Leu, Arg, Ser, Thr, and Val). The amount of three mutant proteins
      (A145E, A145I, and A145L) in cells was too small to allow the measurement of
      circular dichroism (CD) spectra and urea unfolding. The CD spectra of other seven
      mutants were identical with those of the wild-type DHFR, indicating that the
      native conformation of DHFR was not affected by the mutations. The free energy
      change of unfolding by urea decreased with an increase in the hydrophobicity of
      amino acid residues introduced, A145T>A145R>A145G>=A145S>=A145H>A145V++ +>wild
      type>=A145F. The steady-state kinetic parameters for the enzyme reaction, Km and
      ksub, were only slightly influenced by the mutations. These results suggest that
      site 145 in the flexible loop plays an important role in the stability but has
      little or no effect on the native structure and function of this enzyme. The
      characteristics of the mutations are discussed in comparison with those of
      mutations at site 67 [Ohmae et al. (1996) J. Biochem. 119, 703-710] and at site
      121 [Gekko et al. (1994) J. Biochem. 116, 34-41] in two other flexible loops.

PMID- 9562615
TI  - Effect of salts on the solubility of thermolysin: a remarkable increase in the
      solubility as well as the activity by the addition of salts without aggregation
      or dispersion of thermolysin.
AB  - Thermolysin is remarkably activated in the presence of high concentrations (1-5
      M) of neutral salts [Inouye, K. (1992) J. Biochem. 112, 335-340]. The activity is
      enhanced 13-15 times with 4 M NaCl at pH 7.0 and 25 degrees C. In this study, the
      effect of neutral salts on the solubility of thermolysin has been examined.
      Although the solubility was only 1.0-1.2 mg/ml in 40 mM Tris-HCl buffer, pH 7.5,
      in the temperature range between 0 and 60 degrees C, it was increased greatly by
      the addition of salts. With NaCl, the solubility showed a bell-shaped behavior
      with increasing NaCl concentration, and the maximum solubility (10 mg/ml) was at
      2.0-2.5 M NaCl. With LiCl and NaI, it increased progressively to 20-50 mg/ml with
      increasing salt concentration up to 5 M. The solubility observed in the presence
      of salts decreased with increasing temperature from 0 to 60 degrees C, and also
      with the order of chaotropic anion effect. The molecular weight of thermolysin
      was estimated to be 33.0(+/-2.5) x 10(3) in the presence of 0-3 M NaCl,
      suggesting that thermolysin exists as a monomer in the presence or absence of 3 M
      NaCl. The possibility that aggregation and/or dispersion of thermolysin might be
      related to the remarkable activation by salt was ruled out.

PMID- 9562616
TI  - Effect of B. subtilis TRNA(Trp) on readthrough rate at an opal UGA codon.
AB  - Bacillus subtilis has been thought to have a high readthrough rate at the UGA
      stop codon because no opal suppressor tRNA has been isolated so far [Lovett et
      al. (1991) J. Bacteriol. 173, 1810-1812]. To examine whether a tRNATrp which we
      have characterized [Matsugi et al. (1992) Nucleic Acids Res. 20, 3514] has the
      ability to read the UGA codon, in vitro translation was performed with a
      synthetic mRNA containing a test codon, UGA, UAG, UAA, or UGG, in a reading
      frame. Addition of Trp-tRNATrp to the system significantly increased the
      readthrough rate only in the case of UGA. This suggests that this tRNATrp has a
      dual recognition pattern in B. subtilis, i.e., for the canonical tryptophan codon
      and for readthrough at the UGA stop codon.

PMID- 9562617
TI  - Enzymatic synthesis of 14C-glycosphingolipids by reverse hydrolysis reaction of
      sphingolipid ceramide N-deacylase: detection of endoglycoceramidase activity in a
      seaflower.
AB  - This paper describes the synthesis of 14C-labeled glycosphingolipids using the
      reverse hydrolysis reaction (condensation) of sphingolipid ceramide N-deacylase.
      It was found that 50-70% of 14C-fatty acids were incorporated into various lyso
      glycosphingolipids when a mixture of lyso-glycosphingolipids and fatty acids was
      incubated at 37 degrees C with 1 mU of the enzyme for 20 h in 1 ml of 25 mM
      phosphate buffer, pH 6.0-7.0, containing 0-0.1% Triton X-100. The optimum
      concentration of lyso-glycosphingolipids was 100-400 microM depending on the
      species of lyso-form when [14C]stearic acid was used at the concentration of 100
      microM. Free 14C-fatty acids and lyso-glycosphingolipids were separated from the
      synthesized 14C-glycosphingolipids by using a Sep-Pak Plus Silica and a Sep-Pak
      CM or a QMA cartridge, respectively. After treatment of 14C-glycosphingolipids
      with endoglycoceramidase or sphingolipid ceramide N-deacylase, digestion products
      were clearly separated from the parent glycosphingolipids on TLC and determined
      using an image analyzer with a sensitivity 100 times higher than that using non
      radiolabeled substrates. Using this method, we found endoglycoceramidase activity
      in a seaflower, Condylactis sp., for the first time.

PMID- 9562618
TI  - Increased serum midkine levels during hemodialysis using heparin in chronic renal
      failure.
AB  - The heparin-binding growth factor midkine (MK) has been implicated in neuron
      growth, angiogenesis, and inflammation. In this study, to elucidate the
      involvement of MK in the development of pathologies associated with uremia, we
      examined the serum MK levels in patients receiving hemodialysis (HD) by a highly
      sensitive enzyme-linked immunoassay. Although no significant difference was found
      between control serum and serum before dialysis in HD patients, serum MK levels
      increased significantly at the early stage of HD sessions using heparin and
      gradually decreased after dialysis. In normal controls, intravenous
      administration of heparin induced a similar sudden increase of MK, but the
      subsequent decrease was also rapid. In an in vitro study, MK was released in time
      and heparin-dose dependent manner from cultured vessels, but not from peripheral
      leukocytes. These results indicate that, in HD patients, MK is released mainly
      from endothelial cells immediately after administration of heparin during HD and
      disappears gradually from blood due to renal impairment. This phenomenon might
      affect some complications associated with HD.

PMID- 9562619
TI  - Identification of lipid inhibitor of mammalian phospholipase D.
AB  - Phospholipase D (PLD) is implicated in important cellular processes, such as
      hormone action, inflammation, secretion, mitogenesis, and neural activity. Recent
      studies using cell-free systems have shown that the enzyme activity is modulated
      by both positive and negative regulators. During an attempt to purify PLD from
      pig colon mucosa, we noted the presence of a PLD inhibitor in the tissue extract.
      The inhibitor was purified and identified as comprising lysophosphatidylserine,
      phosphatidylinositol, and lysophosphatidylinositol, of which
      lysophosphatidylserine was the most potent. These lipids affected all of the PLD
      isoforms examined, oleate-dependent PLD, ARF-dependent PLD (PLD1a, PLD1b), and
      phosphatidylinositol 4,5-bisphosphate-dependent PLD (PLD2), in the concentration
      range of the 1 or 10 microM order. In contrast to lysophosphatidylserine, the
      diacyl counterpart phosphatidylserine was without effect in the same
      concentration range. PLD inhibition by lysophosphatidylserine could not be
      reversed by an increase in the concentration of the substrate phosphatidylcholine
      or activator phosphatidylinositol 4,5-bisphosphate.

PMID- 9562620
TI  - Cloning and characterization of three isoforms of OS-9 cDNA and expression of the
      OS-9 gene in various human tumor cell lines.
AB  - OS-9 gene is frequently coamplified with CDK4 gene in human sarcomas. We isolated
      and characterized three isoforms of OS-9 cDNA found in a myeloid leukemia HL-60
      cDNA library. Isoform 1 consisted of 2,700 bp, from which a 667 amino acid
      sequence was deduced and found to be identical with that of OS-9 cDNA from
      osteosarcoma cells [Su et al. (1996) Mol. Carcinogen. 15, 270-275]. Isoform 2
      cDNA lacked a 165 nucleotide sequence in the coding region. Isoform 3 cDNA had an
      additional 45 bp deletion in the coding region. Isoforms 2 and 3 encode 612 and
      597 amino acid polypeptides, respectively. Comparison of their cDNA sequences
      with the genomic structure indicated that three isoforms are splice variants.
      Reverse transcription-polymerase chain reaction analysis showed predominant
      expression of isoform 2 mRNA in myeloid leukemia HL-60 cells, osteosarcoma OsA-CL
      cells and rhabdomyosarcoma Rh30 cells. Northern blotting revealed similar levels
      of expression of OS-9 gene in various tumor cell lines of sarcoma cells,
      carcinoma cells and myeloid leukemia cells, but 3-4 times higher expression in
      OsA-CL cells and Rh30 cells containing a homogeneously staining region of 12q13
      15. OS-9 expression decreased in differentiation-induced HL-60 cells. Possible
      involvement of the OS-9 gene in cell growth is discussed.

PMID- 9562621
TI  - Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces
      cerevisiae dis3.
AB  - Saccharomyces cerevisiae Dis3p, which interacts with Ran/Gsp1p, complements
      Schizosaccharomyces pombe dis3-54. Consistent with the functional conservation of
      Dis3p in S. cerevisiae and S. pombe, the human ORF (accession number: R27667) was
      found to be highly homologous to yeast Dis3p. Based on its nucleotide sequence,
      we cloned a full-sized human DIS3 cDNA. The cloned human cDNA partly but
      significantly restored the temperature-sensitivity of S. cerevisiae dis3. Thus,
      Dis3p was found to be structurally and functionally conserved from yeast to
      mammals. Consistent with the report that S. cerevisiae Dis3p is identical to
      Rrp44p, which comprises the exosome involved in ribosomal RNA processing, S.
      cerevisiae Dis3p was found to be localized in the nucleolus. Similar to S.
      cerevisiae Dis3p, human Dis3p enhanced RCC1-stimulated nucleotide release from
      Ran, in a dose-dependent manner, and bound to GTP- or GDP-Ran.

PMID- 9562622
TI  - Cloning and expression of the gene encoding flavodoxin from Desulfovibrio
      vulgaris (Miyazaki F).
AB  - The gene encoding a flavodoxin of Desulfovibrio vulgaris (Miyazaki F) was cloned,
      and overexpressed in Escherichia coli. A 1.6-kbp DNA fragment, isolated from D.
      vulgaris (Miyazaki F) by double digestion with SalI and EcoRI, contained the
      flavodoxin gene and its regulatory region. An expression system for the
      flavodoxin gene under control of the T7 promoter was constructed in E. coli. The
      purified protein was soluble and exhibited a characteristic visible absorption
      spectrum. HPLC analysis of the recombinant flavodoxin revealed the presence of an
      identical FMN to that found in the native D. vulgaris flavodoxin, and its
      dissociation constant with FMN was determined to be 0.38 nM. In vitro H2
      reduction analysis indicated that the recombinant flavodoxin is active, and its
      redox potential was determined to be E1 = -434 and E2 = -151 mV using methyl
      viologen and 2-hydroxy-1,4-naphthoquinone, respectively. Its redox behavior was
      also examined with the recombinant flavodoxin adsorbed onto a graphite electrode.
      The mutant, A16E, was also produced, which revealed the feature of a conserved
      Glu residue at the surface of the molecule.

PMID- 9562623
TI  - Purification and characterization of a membrane-associated ganglioside sialidase
      from bovine brain.
AB  - A membrane-associated ganglioside-hydrolyzing sialidase was purified to apparent
      homogeneity from bovine brain. The enzyme was solubilized with Triton X-100 plus
      sodium cholate from the particulate fraction and purified over 100,000-fold by
      sequential chromatography on DEAE-cellulose, octyl-Sepharose, heparin-Sepharose,
      Sephacryl S-200, MonoQ, RCA-agarose, thiol-activated Sepharose, and ganglioside
      affinity Sepharose. The final enzyme preparation exhibited a specific activity of
      4,851.3 micromol/h/mg protein and an apparent molecular mass of 52 kDa on SDS
      polyacrylamide gel electrophoresis. The enzyme preferentially hydrolyzed
      gangliosides other than GM1 and GM2 but demonstrated hardly any activity against
      glycoproteins and oligosaccharides. Gangliosides GD3, GD1a, and GT1b were much
      better substrates than GM3 and GD1b in the presence of Triton X-100, but the
      latter became more sensitive to the sialidase with addition of sodium cholate.
      The enzyme was activated by dithiothreitol, strongly inhibited by 4-hydroxy
      mercuribenzoate, and firmly adsorbed to thiol-activated Sepharose, indicating
      that free sulfhydryl groups are essential for its catalytic activity. Subcellular
      fractionation experiments revealed that the enzyme is mainly located in the
      synaptosomal fraction.

PMID- 9562624
TI  - Substrate specificity and some other enzymatic properties of dihydroceramide
      desaturase (ceramide synthase) in fetal rat skin.
AB  - Dihydroceramide desaturase, which catalyzes the introduction of a double bond at
      the 4,5-position of the sphingosine base in a dihydroceramide, was assayed in
      vitro using radiolabeled D-erythro-C18-dihydroceramide (N-stearoyl sphinganine)
      and homogenates of fetal rat skin, and some enzymatic properties, including
      substrate specificity, were determined. The ceramide structure, as the enzymatic
      product, was confirmed by (i) oxidation of the product with 2,3-dicyano-5,6
      dichlorobenzoquinone, which revealed the conversion to 3-ketoceramide (3,3'
      didehydroceramide), indicating that a double bond was introduced at the adjacent
      to the C-3 hydroxyl residue of sphinganine, and (ii) mass spectrometry of a long
      chain base released from the enzymatic product, which revealed a spectrum
      identical to that of authentic sphingenine. A short chain dihydroceramide, which
      was radiolabeled at sphinganine through a newly established method, having a C2-
      or C6-fatty acid was not desaturated by the skin enzyme, whereas that having a
      C10-, C14-, or C18-acid was desaturated, maximal reactivity being observed for
      the C14-dihydroceramide. Other enzymatic properties were confirmed: NAD(H) or
      NADP(H) and a detergent were required for elevation of the activity; the optimum
      pH was approximately 6.7; and metal cations were not essential, but Zn2+, Cu2+,
      and Fe2+ were rather inhibitory. These properties of rat skin desaturase were
      partly similar to those of rat liver microsomes, as reported recently, however,
      their substrate specificities were different.

PMID- 9562625
TI  - Functional expression of the human UDP-galactose transporters in the yeast
      Saccharomyces cerevisiae.
AB  - We describe the functional expression of the putative human Golgi UDP-galactose
      transporters (hUGT1 and hUGT2) in the yeast Saccharomyces cerevisiae. Both hUGT1
      and hUGT2 were expressed under the control of the yeast constitutive GAPDH
      promoter. The expression level of hUGT1 seemed to be considerably lower than that
      of hUGT2, although hUGT1 has an amino acid sequence identical to that of hUGT2
      except for 5 amino acid residues at the C-terminus. The hUGT product was
      expressed in the membranes of Golgi and other organellar compartments. The
      membrane vesicles prepared from the hUGT1- or the hUGT2-expressing yeast cells
      exhibited UDP-galactose specific transport activity. The apparent Km values of
      the yeast-expressed hUGT1 and hUGT2 for UDP-galactose were 1.2 and 2 microM,
      respectively, which were comparable with the Km obtained with mammalian Golgi
      vesicles. Transport was dependent on temperature and integrity of vesicles, and
      was inhibited by UMP, as observed with mammalian Golgi vesicles. Our results
      demonstrate that the previously described hUGT1 and hUGT2 encode the UDP
      galactose transporters, rather than regulatory proteins. The development of a
      convenient yeast expression system should facilitate analysis of the structure
      function relationships of the UDP-galactose transporters.

PMID- 9562626
TI  - Validation of malondialdehyde and 4-hydroxy-2-trans-nonenal measurement in plasma
      by NICI-GC-MS.
AB  - Measurement of the concentrations of aldehydes in biological samples has become
      the object of much effort due to their relevance in relation to the toxic effects
      of lipid peroxidation, through which a number of aldehydes are derived. We have
      reconsidered a previously proposed method based on gas chromatographic mass
      spectrometric analysis of derivatives obtained by the treatment of aldehydes with
      O-pentafluorobenzyl hydroxylamine followed by a trimethylsilylating agent. In
      view of the possible use of the method for the simultaneous evaluation of the
      plasma levels of malondialdehyde and 4-hydroxy-2-trans-nonenal, we have studied
      the linearity of the analysis using various internal standards. Commercially
      available, inexpensive 2,4-dihydroxybenzaldehyde gave optimal results, the
      correlation coefficient of the calibration curve for plasma being r > 0.995 in
      the 0.1-5 microM range for both the tested aldehydes. The between-day imprecision
      (%CV) and accuracy (%bias) of the procedure determined using plasma samples
      spiked with the two aldehydes and with an internal standard reached maximum
      values of 3 and 8%, and 5 and 12% for HNE and MDA, respectively. The results
      obtained on analysis of plasma samples before and after oxidation with copper
      ions indicate the flexibility of the method for evaluation of the levels of MDA
      and HNE in plasma samples both under basal conditions and after an oxidative
      burst.

PMID- 9562627
TI  - Identification of the catalytic triad residues of porcine liver acylamino acid
      releasing enzyme.
AB  - Acylamino acid-releasing enzyme (AARE) [EC 3.4.19.1] is a tetrameric serine
      protease, which belongs to the oligopeptidase family and specifically removes
      acetyl amino acids from N-terminally acetylated peptides. By using diisopropyl
      fluorophosphate, we previously identified one of the residues comprising the
      catalytic triad of this enzyme as Ser587 [Miyagi, M. et al. (1995) J. Biochem.
      118, 771-779]. To elucidate the other two residues forming the catalytic triad of
      this new serine-type protease, wild-type and four mutant AAREs, in which each
      candidate residue of the catalytic triad deduced from sequence alignment with
      other oligopeptidases was substituted by site-directed mutagenesis, were
      expressed in Escherichia coli as fusion proteins with short peptide chains at
      both N- and C-termini of a subunit of porcine liver enzyme. All of the
      recombinant AAREs were estimated to have similar conformational and quaternary
      structures to the native porcine liver enzyme from their CD spectra and behavior
      on gel-filtration, but the mutants in which Ala587, Asn675, or Tyr707 was
      substituted for Ser587, Asp675, or His707, respectively, did not show detectable
      hydrolytic activity toward acetyl-L-methionyl L-alanine. These facts suggest that
      Ser587, Asp675, and His707 are essential residues for the AARE activity and
      comprise the catalytic triad of the enzyme in this order. Thus, AARE has been
      shown to have a protease-like domain in its C-terminal region, as do other
      proteins classified as members of the oligopeptidase family.

PMID- 9562628
TI  - An assay method for glycogen debranching enzyme using new fluorogenic substrates
      and its application to detection of the enzyme in mouse brain.
AB  - An assay method for glycogen debranching enzyme involving fluorogenic dextrins as
      substrates was developed. Two dextrins were prepared from 6-O-alpha-D-glucosyl
      alpha-cyclodextrin and glucose by taking advantage of the action of Bacillus
      macerans cyclodextrin glucanotransferase, and converted by pyridylamination to
      fluorogenic derivatives. Structural analysis of the fluorogenic dextrins by FAB
      MS, partial acid hydrolysis, and glucoamylase digestion revealed that they were
      Glcalpha1-4(Glcalpha1-6)Glcalpha1-4Glcalpha1- 4Glcalpha1-4Glc-PA (FD6) and
      Glcalpha1-4Glcalpha1-4(Glcalpha1-6)Glcalpha1- 4Glcalpha1-4Glcalpha1-4G lc-PA
      (FD7). Using the glycogen debranching enzyme from rabbit muscle, FD6 and FD7
      were, respectively, hydrolyzed to PA-maltopentaose and PA-maltohexaose, in
      addition to glucose, showing that these two fluorogenic dextrins are suitable
      substrates for assaying the glycogen debranching enzyme. An assay method
      involving the separation and quantification by HPLC of the characteristic
      fluorogenic products was successfully applied to determination of the
      distribution of the enzyme activity in mouse cerebrum.

PMID- 9562629
TI  - Diversity of capsular polysaccharide synthesis gene clusters in Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae comprises 90 serotypes, each one having its own specific
      polysaccharide capsule. In order to explore the diversity of capsular
      polysaccharide synthesis (cps) gene clusters in S. pneumoniae, we performed cross
      hybridizations between the 12 cps genes of S. pneumoniae serotype 14 and
      chromosomal DNA of 26 strains comprising 26 different capsule types. Large
      variations in the hybridization patterns were observed. The genes cps14A to
      cps14D are conserved in most serotypes. Sequences homologous to cps14I to cps14L
      were only observed in the four types of serogroup 15, which all have a capsule
      structure similar to that of type 14. By using a cps14E knock-out construct, cpsE
      mutants of the pneumococcal types 9N, 13, and 15B were obtained. These mutants
      were unencapsulated and showed reduced glycosyltransferase activity, indicating
      that the pneumococcal types 9N, 13, and 15B express a glucosyl-1-phosphate
      transferase which is homologous to Cps14E. Glycosyltransferase assays showed that
      among 21 pneumococcal types which contain glucose in the core of their capsule
      polysaccharide, 19 types express glucosyl-1-phosphate transferase activity.
      However, not all of these types hybridized strongly with Cps14E, the type 14
      glucosyl-1-phosphate transferase gene. Thus, pneumococci possess
      glucosyltransferase genes distinct from cps14E, but encoding enzymes with
      identical activity. All serotypes which synthesized lipid-linked lactose
      intermediates in glycosyltransferase activity assays (type 11B, 13, 15F, 15A,
      15B, 15C) hybridized with cps14G. This gene encodes a galactosyltransferase which
      catalyzes the addition of 1,4-linked beta-galactose to lipid-linked glucose. The
      cps14G homologues in type 11B, 13, 15F, 15A, 15B, and 15C may encode a similar
      beta-galactosyltransferase activity as cps14G in type 14.

PMID- 9562630
TI  - Actin-binding specificity of marine macrolide toxins, mycalolide B and kabiramide
      D.
AB  - An actin-depolymerizing marine natural product, mycalolide B, and a related
      compound, kabiramide D, were labeled with biocytin, a biotin derivative, and used
      to specify target molecules in cultured rat 3Y1 fibroblasts. Mycalolide B
      exhibited the ability to bind to various intracellular proteins, probably through
      the Michael addition of a sulfhydryl group to C5 of mycalolide B. However, no
      intracellular proteins other than actin apparently reacted with biocytinylated
      kabiramide D, demonstrating that the binding of kabiramide D to actin was highly
      specific. Cells treated with biocytinylated kabiramide D followed by staining
      with fluorescein isothiocyanate-conjugated avidin showed that biocytinylated
      kabiramide D bound to stress fibers composed of F-actin, although the staining
      intensity was weaker than the fluorescent phalloidin staining. The assay for the
      binding of kabiramide D to actin, which had previously been treated with other
      actin-depolymerizing agents, showed that the actin-binding site for kabiramide D
      was the same as that for bistheonellide A, but not those for latrunculin A and
      cytochalasin D.

PMID- 9562631
TI  - Isomerization of 11-cis-retinol to all-trans-retinol in bovine rod outer
      segments.
AB  - It is known that exogenous 11-cis-retinol inhibits the recovery of
      photosensitivity of bleached rod outer segments (ROS) and 11-cis-retinol exists
      in the interphotorecepter matrix. We examined the conversion of 11-cis-retinol
      with bovine ROS. ROS was incubated with 11-cis-retinol under dim red light.
      Retinoids were extracted from the reaction mixture with hexane and analyzed by
      HPLC coupled with a fluorescence spectrophotometer. Isomerization of 11-cis
      retinol to all-trans-retinol was observed in the presence of ROS. This
      isomerization was not suppressed by heat treatment and did not have
      stereospecificity. In addition, we incubated purified rhodopsin and phospholipids
      extracted from ROS with 11-cis-retinol. Rhodopsin was found to isomerize 11-cis
      retinol to all-trans-retinol as well as ROS, but phospholipids did not. In
      contrast, the phospholipids inhibited the isomerization of 11-cis-retinol to all
      trans-retinol by the purified rhodopsin. Commercially available phospholipids,
      especially phosphatidylserine, also inhibited the isomerization. Our results
      suggest that rhodopsin has activity for the isomerization of 11-cis-retinol to
      all-trans-retinol and may play an important role in the detoxification of 11-cis
      retinol in the ROS.

PMID- 9562632
TI  - The mechanism by which proteolysis enhances the ligand-binding activity of guinea
      pig type II Fc receptor for IgG (FcgammaRIIB).
AB  - We have previously shown that the ligand-binding activity of type II Fc receptor
      for IgG (FcgammaRIIB) on guinea pig peripheral blood polymorphonuclear leukocytes
      is very low and dramatically increases after treatment of the cells with
      proteolytic enzymes. In the present study, we analyzed the mechanism of this
      augmentation. We found that the protease treatment failed to enhance the binding
      of monomeric IgG to FcgammaRIIB, increased the binding of small immune complexes
      (IC) prepared under antigen-excess conditions only modestly, but markedly
      enhanced the binding of large IC prepared under antibody-excess conditions. These
      results suggest that proteolysis increases the ligand-binding avidity but not the
      intrinsic affinity of FcgammaRIIB. Confocal laser scanning microscopy revealed
      that the mobility of FcgammaRIIB on the cell surface was increased after protease
      treatment. In addition, transfection experiments indicated that the effect of
      proteolysis on IC binding to CHO cells expressing guinea pig FcgammaRIIB was
      strongly dependent on the receptor density. Finally, we demonstrated that the
      transmembrane and cytoplasmic domains of FcgammaRIIB were not involved in the
      proteolysis-induced augmentation of IC binding. Together our results suggest that
      the mobility of FcgammaRIIB, which may be restricted due to the association of
      the ectodomain of the receptor with unknown membrane proteins, is enhanced by
      proteolysis, allowing the receptors to bind multivalent ligands more readily and
      hence with higher avidity.

PMID- 9562633
TI  - Defective intracellular transport of tissue-nonspecific alkaline phosphatase with
      an Ala162-->Thr mutation associated with lethal hypophosphatasia.
AB  - We have studied the biosynthesis and intracellular transport of tissue
      nonspecific alkaline phosphatase (TNSALP) transiently expressed in COS-1 cells.
      Mutations were introduced into TNSALP to examine the effects of a single amino
      acid substitution on the activity and biosynthesis of TNSALP. The cells
      expressing wild-type TNSALP exhibited more than 200-fold higher alkaline
      phosphatase activity than untransfected ones. Pulse-chase experiments showed that
      TNSALP was synthesized as a 66-kDa endoglucosaminidase H (Endo H)-sensitive form
      and converted to EndoH-resistant forms with heterogenous molecular masses (
      approximately 80 kDa), which finally appeared on the cell surface as judged by
      digestion with phosphatidylinositol-specific phospholipase C (PI-PLC). In
      contrast, a TNSALP with a Glu218-->Gly mutation exhibited no phosphatase activity
      at all and the 66-kDa Endo H-sensitive form was the only molecular species
      throughout the chase in the transfected cells. In accordance with this finding,
      digestion with PI-PLC and immunofluorescence observation confirmed that this
      mutant was never expressed on the cell surface. Another mutant with a Ala162-
      >Thr substitution, which naturally occurs in association with a lethal
      hypophosphatasia, exhibited a low activity and only a small fraction of the 66
      kDa form acquired Endo-H resistance and reached the cell surface. Since the wild
      type and the mutant TNSALPs were labeled with [3H]ethanolamine, a component of
      glycosylphosphatidylinositol (GPI), it is unlikely that the impaired
      intracellular transport of the two mutants is due to a failure in their
      modification by GPI. Interestingly, the 66-kDa Endo H-sensitive form of the
      TNSALP mutants but not that of the wild-type, was found to form an interchain
      disulfide-bonded high-molecular-mass aggregate within the cells. These results
      suggest that impaired intracellular transport of the TNSALP (Ala162-->Thr)
      molecule caused by its aggregation is the molecular basis for the lethal
      hypophosphatasia carrying this mutation.

PMID- 9562634
TI  - Structure and distribution of N-glycans on the S7-allele stylar self
      incompatibility ribonuclease of Nicotiana alata.
AB  - S-RNases are the stylar products of the self-incompatibility (S)-locus in
      solanaceous plants (including Nicotiana alata), and as such, are involved in the
      prevention of self-pollination. All cDNA sequences of S-RNase products of
      functional S-alleles contain potential N-glycosylation sites, with one site being
      conserved in all cases, suggesting that N-glycosylation is important in self
      incompatibility. In this study, we report on the structure and localization of
      the N-glycans on the S7-allele RNase of N. alata. A total of nine N-glycans,
      belonging to the high-mannose- and xylosylated hybrid-classes, were identified
      and characterized by a combination of electrospray-ionization mass-spectrometry
      (ESI-MS), 1H-NMR spectroscopy, and methylation analyses. The glycosylation
      pattern of individual glycosylation sites was determined by ESI-MS of the glycans
      released from isolated chymotryptic glycopeptides. All three N-glycosylation
      sites showed microheterogeneity and each had a unique complement of N-glycans.
      The N-glycosylation pattern of the S7-RNase is significantly different to those
      of the S1- and S2-RNases.

PMID- 9562636
TI  - Prevention, not just treatment.
AB  - A tragic burden of disease, disability, and death has resulted from smoking. The
      role of pulmonary rehabilitation is not only in treatment and rehabilitation of
      lung disease but in the prevention of lung disease. The skills of the pulmonary
      rehabilitation specialist should be used in the earlier detection and prevention
      of lung disease through primary and secondary prevention. The spirometer must
      gain acceptance in the medical community as the early tool to evaluate lung
      health, not the chest radiograph or the stethoscope. The lung age formula and
      sputum pap smears are just a few of the evaluation tools used to detect and
      motivate susceptible individuals. Prevention is the key to enhancing lung health.

PMID- 9562635
TI  - Enhancer-dependent, locus-wide regulation of the imprinted mouse insulin-like
      growth factor II gene.
AB  - The mouse insulin-like growth factor II (IGF-II) gene is subject to parental
      imprinting and is predominantly expressed from the paternal chromosome. This
      allele-specific expression is modified further by cell type, developmental stage,
      and growth conditions. We show that the ratio of the three major IGF-II mRNAs,
      each produced from a distinct promoter, is consistent in a variety of tissues and
      cells representing different modes and phases of the complex regulation. Nuclear
      run-on assays show that the major changes in total IGF-II mRNA level occur at the
      level of transcription. Moreover, a targeted disruption of the endoderm-specific
      enhancers, located 90 kb away from the gene, affects all promoters. The
      dependency of the promoters on distal enhancers is also shown by transgenesis
      experiments. Our findings suggest that enhancer-dependent, locus-wide mechanisms
      play a major role in the coordinate regulation of the multiple IGF-II promoters.

PMID- 9562637
TI  - Vignettes of a pulmonary rehabilitation team.
AB  - A successful comprehensive pulmonary rehabilitation program depends on these key
      pieces: thorough planning, an experienced coordinator who is a patient advocate,
      a dedicated and supportive medical director, enthusiastic and committed team
      members, the use of program graduates as volunteers, and providing the essential
      components of pulmonary rehabilitation, which consist of assessment, patient
      training, exercise, psychosocial intervention, and follow-up. The patients are
      the most important members of the team. Their courage, dedication, and
      determination to make their quality of life the best it can be is truly an
      inspiration to all of us.

PMID- 9562638
TI  - The ABCs of patient and rehabilitation specialist training and education.
AB  - In this article the authors consider patient training and education from the
      perspective of training the rehabilitation specialist. Specialist training is a
      process that will enable the specialist to aid the patient and caregiver in the
      acquisition of knowledge, skills, understanding, and a positive outlook as they
      pertain to the management of the patient's medical condition. The ultimate goals
      are to encourage patient and family to participate more fully in health care and
      to allow a more collaborative effort between the health care provider and the
      patient.

PMID- 9562639
TI  - Pulmonary rehabilitation in the acute inpatient rehabilitation hospital.
AB  - In closing, pulmonary rehabilitation in an inpatient rehabilitation hospital is
      not a new idea, but is now becoming more popular as the burden of care shifts
      away from the acute care hospital. Pulmonary rehabilitation has been demonstrated
      to be cost-effective, improve quality of life, and decrease the number of future
      hospital days for the patient. A few surveys have shown, however, that only 5% of
      pulmonary rehabilitation programs serviced inpatients in a rehabilitation
      hospital, and only 1% of 283 programs had a physiatrist as the medical director
      of the pulmonary rehabilitation program. Nine percent of programs surveyed
      serviced inpatients in rehabilitation units within the acute care hospital.
      Clearly, the majority of pulmonary rehabilitation programs are on an outpatient
      basis, and many of these are located within the walls of a rehabilitation
      hospital. Effective pulmonary rehabilitation can be done in the home setting when
      combined with outpatient therapy visits over a 12-week duration. The spectrum of
      pulmonary rehabilitation will continue to evolve into the twenty-first century,
      and clearly the rehabilitation hospital will be part of that change. Whether
      caring for very elderly COPD patients who are too debilitated to return home from
      the acute care hospital or managing ventilator-dependent patients with COPD,
      spinal cord injury, or neuromuscular disease, the IPR team and the rehabilitation
      hospital will have to demonstrate cost-effective outcomes. Physiatrists should
      play a major role in this evolution, on both a patient-benefit level and
      legislative level, to increase awareness of pulmonary rehabilitation.

PMID- 9562640
TI  - Pulmonary rehabilitation of the patient with nonobstructive lung disease.
AB  - Disability from chronic lung disease is usually associated with COPD and
      pulmonary rehabilitation programs are designed to address this population. There
      are a number of chronic nonobstructive lung diseases, however, that can produce
      disability and that also may benefit from pulmonary rehabilitation. This article
      discusses how to classify nonobstructive lung disease patients and examines their
      evaluation, rehabilitation, and outcomes.

PMID- 9562641
TI  - Pulmonary rehabilitation in the surgical patient. Lung transplantation and lung
      volume reduction surgery.
AB  - Prior to lung transplantation or lung volume reduction surgery, patients complete
      a comprehensive pulmonary rehabilitation program. The program aids physicians in
      the selection of appropriate surgical candidates and prepares patients physically
      and psychologically for the stress of surgery. Because lung transplantation often
      involves relocation and prolonged waiting, stress levels can be particularly
      high. Rehabilitation continues through the perioperative and postoperative period
      to facilitate recovery and bring patients to the highest possible level of
      function. Studies of lung transplant recipients suggest that most patients who
      survive to hospital discharge enjoy a significant improvement in pulmonary
      function and many resume work and household responsibilities. Initial experiences
      with lung volume reduction surgery also suggest that many patients experience
      improved dyspnea symptoms and functional status after the procedure. As lung
      transplantation and lung volume reduction surgery emerge as viable therapeutic
      options for many patients with end-stage lung disease, comprehensive pulmonary
      rehabilitation programs are essential to address the complex medical, surgical,
      and psychological issues that surround these procedures and to produce optimal
      therapeutic outcomes.

PMID- 9562642
TI  - Nutritional aspects of lung disease.
AB  - The relationships between dietary intake, ventilatory demand, and respiratory
      muscle function are now well recognized. Malnutrition in patients with advanced
      COPD is associated with adverse effects on respiratory muscle function leading to
      reduced muscle strength and premature mortality. The relationships between
      nutrient intake and the host inflammatory response are just beginning to be
      explored. This article summarizes current knowledge regarding the relationship
      between nutritional status and the lung.

PMID- 9562643
TI  - Outcome measurement in pulmonary rehabilitation.
AB  - The measurement of outcomes of therapy is becoming ever more important as part of
      the overall management of an individual patient. This is particularly true when
      considering pulmonary rehabilitation for a patient with chronic lung disease.
      Health, clinical, and behavioral domains should be assessed when evaluating the
      effectiveness of pulmonary rehabilitation. This assessment of outcomes can be
      easily made using currently available tools.

PMID- 9562644
TI  - How does pulmonary rehabilitation survive in a managed care market?
AB  - As managed care enrollment increases, pulmonary rehabilitation coordinators need
      to become well versed in the terminology and grasp the way managed care
      organizations operate. Maintaining access to pulmonary rehabilitation services
      for chronic lung disease patients is imperative. Learning how to obtain treatment
      referrals and authorizations has become challenging. Using offered resources can
      aid program coordinators in their struggle to survive in an ever-changing health
      care delivery system. Preventative and restorative rehabilitation intervention
      saves utilization of expensive health care resources.

PMID- 9562645
TI  - A practical approach to managing care under managed care. Case examples in
      pulmonary medicine.
AB  - As managed care medicine penetrates the health care marketplace, all those
      involved in the health care delivery process will have to redesign and
      restructure the way they provide health care services. With the current emphasis
      on controlling health care costs, providers will be compelled to come up with the
      successful strategies and methodologies that lead to the delivery of cost
      effective high-quality care with positive, successful patient outcomes. Having
      the capability to analyze the information necessary to identify, measure, and
      monitor processes and outcomes is one of the key critical factors for success.
      Using information to identify opportunities for improvement, developing and
      implementing the appropriate process improvement activities, and being able to
      document and demonstrate the results of one's efforts are crucial for survival in
      a competitive managed care market.

PMID- 9562646
TI  - Collaboration of national organizations and the legislative means to advance
      pulmonary rehabilitation.
AB  - Getting involved in the public policy process empowers health care professionals
      to help ensure the preservation of patient rights. An organization must form
      strong relationships with legislators using simple yet occasionally
      unconventional strategies. Too few patients currently have access to
      rehabilitative services. Passing national legislation promoting patient access to
      pulmonary rehabilitation will have a great impact by enabling more and more
      patients to take advantage of pulmonary rehabilitation programs because they are
      fully reimbursed.

PMID- 9562647
TI  - Plasma proteins glycosylation and its alteration in disease.
AB  - Most plasma proteins are glycoproteins, that is, they possess oligosaccharide
      chains attached to the polypeptide core. These oligosaccharides have important
      structural and functional roles; they serve as recognition markers (ligands),
      especially for lectin receptors, thus modulating the glycoprotein interactions.
      Protein glycosylation is a posttranslational event which depends on the proteic
      core and biosynthetic cell type and results in a set of microheterogeneous forms
      (glycoforms) of an individual glycoprotein. Under pathological conditions an
      alteration of the glycosylation pattern of plasma glycoproteins occurs. So,
      degalactosylated IgG and IgA1 detected in rheumatoid arthritis and IgA
      nephropathy, respectively, are implicated in the pathogenic mechanisms.
      Alteration of transferrin, alpha 1-acid glycoprotein and alpha-fetoprotein
      glycosylation (reduced sialylation and increased branching of oligosaccharide
      chains) occurs in liver diseases. In inflammations and infections the alteration
      is dependent on the disease studied, while increased sialylation and fucosylation
      of acute-phase proteins are detected in cancer sera. Lectin-based methods have
      been developed for clinical purposes, in order to improve the diagnosis,
      prognosis evaluation, or treatment monitoring.

PMID- 9562648
TI  - Effect of isometric effort upon mitral regurgitation severity--echo Doppler
      study.
AB  - Isometric effort increases the severity of mitral regurgitation (MR) by
      augmenting the afterload and the regurgitant fraction. The worsening of MR may be
      different in various patients and can explain the differences in effort capacity
      of patients with identical rest mitral regurgitation. We studied 25 patients with
      MR of various etiologies, submitted to handgrip (maximal voluntary contraction),
      the severity of MR being evaluated by the determination of regurgitant area
      (colour Doppler). There was a 42% increase of the regurgitant area from 3.26 to
      4.66 cm2 (p < 0.05). The increase was greater for ischemic MR (59%) than for MR
      in dilated cardiomyopathy (26%), the last value not being explained by a lower EF
      because rest EF was similar in patients with and without an increase of MR
      severity during maximal voluntary contraction. The individual analysis of the
      results showed an increase of the MR severity in 1/2 of the patients, in whom the
      left atrial dimension was greater, though the effort capacity was the same in the
      two subsets of patients. It is concluded that colour Doppler is a simple and
      valuable method for studying the influence of isometric exercise upon MR
      severity, this being increased in 1/2 of the patients, with a positive
      correlation with ischemic etiology of the disease, left atrial dimension, but not
      with the patients' effort capacity.

PMID- 9562649
TI  - Hemodynamic performances in patients treated with sotalol after electrical
      cardioversion of atrial fibrillation.
AB  - The negative inotropic effect of nearly all antiarrhythmic drugs, especially
      important in patients with impaired left ventricular function, represents a major
      drawback of medical therapy. The aim of this study is to evaluate the atrial and
      ventricular function and the exercise capacity in patients with mild heart
      failure treated with d,l-sotalol after electrical conversion of atrial
      fibrillation. The study included patients with persistent atrial fibrillation
      (for more than 2 weeks but less than 1 year) and mild heart failure (< or = class
      II NYHA). All patients had comparable basal echocardiographic findings, and
      received captopril. After successful cardioversion the patients were randomized
      in two groups: group 1 treated with sotalol (mean dose 240 mg q.d., max. 320 mg)
      and group 2--without sotalol. The drop-out criterion was the failure to maintain
      sinus rhythm. Finally, in the study remained 17 patients (10 men, 7 women, aged
      41-60 years); group 1 included 10 patients and group 2-7 patients. They were
      assessed by quantitative echocardiography + Doppler and by standard ecg exercise
      test at less than 1 month but more than 2 weeks, and at 1, 3, and 6 months. When
      first evaluated (2 weeks-1 month), peak A wave velocity and atrial filling ratio
      were higher in group 2 than in group 1 (37 +/- 10 cm/s vs 20 +/- 5 cm/s and 23%
      +/- 7 vs 13% +/- 5, respectively) and group 1 had also a lower exercise tolerance
      (80 +/- 25 W vs 110 +/- 10 W). There were no significant differences between
      groups 1 and 2 in left atrial and left ventricular dimensions, ejection fraction
      and E wave deceleration time. After 1 month there were no significant differences
      in Doppler characteristics, echocardiographic parameters and exercise tolerance
      between the two groups. Group 1 remained at a lower heart rate and had a lower
      maximal double product (17250 mmHg/min vs 22100 mmHg/min) corresponding to a
      lower cardiac work. At 3 and 6 months there were no significant changes in all
      characteristics between the two groups. In conclusion, sotalol seems to be a well
      tolerated antiarrhythmic agent in patients with mild heart failure, after
      conversion of persistent atrial fibrillation. In this setting: 1. Sotalol could
      reversibly amplify the effect of atrial stunning after electrical cardioversion
      of atrial fibrillation, but this effect is brief. 2. Sotalol has no relevant
      negative inotropic effect, at least not in association with captopril. 3. Sotalol
      improves the effort capacity.

PMID- 9562650
TI  - Immunodetection of modified lipoproteins in plasma and arterial walls of patients
      with coronary heart disease.
AB  - Data from literature indicate that immune processes play an important role in
      atherogenesis. Modified lipoproteins might be immunogenic and generate
      autoantibodies in plasma. To determine whether the level of such circulating
      autoantibodies correlates with the extent of atherosclerosis expressed as
      cholesterol values in plasma (C), very low density (VLDL-C), low density (LDL-C),
      and high density lipoproteins (HDL-C), we compared the level of plasma
      autoantibodies of a group of coronary heart disease patients (CHD-P) with that of
      normal, age-matched donors, with no history of cardiac disease (N). All CHD-P
      (even normocholesterolemic) were characterized by an LDL-C/HDL-C ratio > 4, while
      all N (even hypercholesterolemic) had this ratio < 4. A double level of
      circulating autoantibodies against VLDL and LDL in CHD-P as compared to N group
      was detected. The anti-LDL antibodies level correlated well with LDL-C level and
      was negatively correlated with the age of patients. For tissue localization of
      native and modified LDL (as well as other possibly modified proteins) we used
      immunohistochemical techniques, employing antihuman LDL, antihydroxynonenal
      lysine (HNE-Lys), and antiadvanced glycation end-products (AGE) proteins.
      Antibodies were applied on consecutive cryosections of the aortic arch, valves
      and coronary arteries of CHD-P. The immunodetected antigens were colocalized in
      focal deposits, in the cap and shoulders of the atheroma. Native LDL and modified
      proteins (AGE, HNE-Lys) were detected either diffuse-extracellularly or
      associated with macrophage-derived foam cells and smooth muscle cells of the
      intima. These data indicate the following: a) the existence of an elevated level
      of circulating autoantibodies against VLDL and LDL, which correlates negatively
      with the age of CHD patients; b) the presence of LDL (possibly glycated or
      oxidized) in detectable amounts in the intima of atherosclerosis-affected
      arteries; c) the modified lipoproteins are immunoactive components in the
      atherosclerotic process.

PMID- 9562651
TI  - Ethyl alcohol and dilative cardiomyopathy.
AB  - The ethanol-induced dilative cardiomyopathy has a complex clinical and
      paraclinical picture because of the direct action of the alcohol and the indirect
      action of its metabolites on human myocardium and neuroendocrine system.
      Ventricular arrhythmias, atrial arrhythmias, and heart failure are significant
      and show a great sensitivity of the conduction system. Working myocardium is also
      affected, which is proved by the impaired systolic and diastolic function of the
      heart and by the nitroglycerine-resistant isovolumetric relaxation time.

PMID- 9562652
TI  - Rapid infusion of streptokinase standard dose in acute myocardial infarction is
      followed by a higher rate of coronary reperfusion than standard protocol.
AB  - There are several opinions asserting that the accelerated t-PA is more efficient
      than the standard protocol of streptokinase (SK) administration in acute
      myocardial infarction (AMI). One hundred patients admitted within the first 6 hrs
      after the onset of the symptoms revealing AMI were divided in two subgroups, as
      follows: subgroup A (50 patients) in whom a dose of 1.5 M.U. SK was infused in 20
      min (accelerated protocol) and subgroup B (50 patients) in whom the same dose was
      infused in 60 min (standard protocol). In order to assess the efficiency of
      thrombolytic therapy (TT), we used three noninvasive criteria: the rapid
      resolution of the chest pain, the rapid decreasing of the ST segment elevation by
      more than 50% from the initial value, and the rapid increasing of enzymes
      revealing necrosis. Using the above-mentioned criteria, we considered that
      coronary reperfusion appeared in 40 patients from subgroup A (80%) and in 29
      patients from subgroup B (58%). The speed of coronary reperfusion was 40 +/- 26
      min in patients with accelerated SK and this time was significantly shorter than
      the time of 60 +/- 24 min registered in the control group. No major hemorrhagic
      events appeared in both subgroups. Although hypotension appeared more frequently
      in subgroup A, this minor complication was well supported by our patients. The
      rapid infusion of the standard dose of SK was followed by a higher rate and speed
      of coronary reperfusion as compared to the standard protocol.

PMID- 9562654
TI  - Distribution of birth dates in type 1 diabetic patients versus nondiabetic
      controls.
AB  - The aim of our study was to analyze the temporal relationship between birth date
      and the onset of insulin-dependent diabetes mellitus (IDDM). Because IDDM is a
      disease with a strong genetic base, we analyzed in this study the monthly
      distribution of births of 900 type 1 diabetic patients with onset of diabetes
      before the age of 20, and 7,839 births registered in 3 consecutive years (1990
      1992) in a district of Bucharest, with a population of about 250,000 inhabitants.
      We observed that the monthly distribution of births in both nondiabetic and
      diabetic populations was not uniform. In nondiabetic population the maximum
      number of births was recorded in June (9.57% of all cases) and the minimum one in
      November (6.45%), giving a difference of percentage between them of 3.12%. In
      diabetic population the difference was significantly higher than in nondiabetic
      individuals (Chi square = 3.408, for a confidence of 90%, p < 0.01). The maximum
      percentage of births was recorded in April (11.56%) and the minimum in January
      (6.22%) with a difference between them of 5.3%. For diabetic population, there
      were two months (April and March) in which the number of births was higher (a
      susceptibility to type 1 diabetes?) and two (January and October) in which the
      number of births in diabetic subjects was lower (resistance to type 1 diabetes?).
      If this pattern of seasonality of births in diabetic patients vs nondiabetic
      individuals will be confirmed on a larger number of subjects, then one possible
      explanation could be the genetic susceptibility or resistance to type 1 diabetes
      in different groups of subjects.

PMID- 9562653
TI  - Influence of natural antioxidants on in vitro lipoprotein oxidation.
AB  - Susceptibility of low-density lipoproteins (LDL) to oxidation might be a critical
      risk factor in the development and progression of atherosclerosis. The oxidation
      involves the degradation of polyunsaturated fatty acids, the formation of
      lysolecithin, oxysterols and aldehyde modification of lysine residues on Apo
      B100. The oxidation products have a number of biological activities such as
      cytotoxicity, atherogenesis, and carcinogenesis. The aim of this study was to
      investigate the in vitro antioxidant effects of vitamins E, A, and C on LDL. LDL
      was isolated from plasma by density gradient high-speed centrifugation and used
      as 0.1 microM/l isotonic solution. LDL oxidation was triggered by simple
      incubation with Cu2+ (1, 2, 5, 10, 12, 20 microM/l), in absence or presence of
      lipid-soluble or water-soluble antioxidants in different concentrations
      (tocopherols--0.5, 1, 2, and 4 microM/l; cerotenoids--0.1, 0.2, and 0.4 microM/l;
      ascorbate--2.5, 5, and 10 microM/l). The LDL oxidability was measured by
      continuous spectrophotometrical monitoring at 234 nm of the increased formation
      of conjugated diene hydroperoxides. The oxidation curves showed a profile with an
      inhibition period followed by a propagation period and were quantitatively
      characterized by two parameters: lag-phase (expressed in minutes), and
      propagation rate (expressed in changes of absorbance--delta E234nm/min). Lag
      phase--the period of inhibition oxidation--was attributed to the ability of LDL
      (by antioxidants) to resist oxidation in vitro. LDL lag-phase decreased and
      propagation rate increased with the increasing of copper concentration. IN
      CONCLUSION: 1) susceptibility of LDL to oxidation depends on both the
      concentration of pro-oxidant stimuli and the entity and concentrations of
      antioxidants; 2) antioxidants retard the process through which LDL undergo
      oxidation in vitro when exposed to copper ions; 3) a synergistic effect may also
      be involved, as water-soluble vitamin C keeps the fat-soluble vitamin E and
      vitamin A within LDL.

PMID- 9562655
TI  - Markers of tissue response to thyroid hormones in patients with hyperthyroidism
      or hypothyroidism.
AB  - Changes in serum cholesterol and aminoterminal type III procollagen propeptide
      (PIIIPN) were compared in 33 patients with hyperthyroidism, 16 patients with
      hypothyroidism, and 23 healthy individuals. An increase in PIIIPN was found in
      patients with hyperthyroidism and an increase in serum cholesterol level was
      associated with hypothyroidism. There was no correlation between investigated
      indices. It is suggested that PIIIPN changes were a result of altered connective
      tissue metabolism, while serum cholesterol was related to the intensity of body
      metabolism.

PMID- 9562656
TI  - Relationship between serum total sialic acid and C-reactive protein in silicosis.
AB  - Serum total sialic acid and C-reactive protein (CRP) were studied in 68 patients
      with silicosis divided into 3 groups according to the evolutive stage of disease.
      The results were compared with the data obtained in a control group of 35 healthy
      subjects. The changes in serum total sialic acid levels were in parallel with
      those of CRP in silicosis. Patients in stage III had the highest mean values of
      serum total sialic acid (p < 0.01) and of CRP (p < 0.001). Linear regression
      analysis revealed a close positive correlation between serum total sialic acid
      and CRP levels in silicosis (r = 0.86, p < 0.01).

PMID- 9562657
TI  - Serological level of ICAM and ELAM adhesion molecules in allergic vascularitis.
AB  - A 24-patient lot with hypersensitivity vasculitis was investigated for
      serological determinations of ICAM and ELAM adhesion molecules. Determinations
      were made in attack and in remission. Over two thirds of the cases presented
      elevated serological levels of ICAM and ELAM in attack, with twofold higher
      values than normal. In remission, in the absence of clinical signs, ICAM and ELAM
      values were normal in 19 cases (ICAM) and 22 cases (ELAM). Serological level of
      ICAM and ELAM was concordant with serological level of IL-2, IL-6, circulating
      immune complexes and clinical status. The increased values of ICAM and ELAM are
      due to the expression of these molecules both on the surface of endothelial cells
      and on immune cells. The adherence of leukocytes on the endothelial cells, by
      adhesion molecules involvement, followed by their extravasation represents an
      important event in the vascular lesion pathogeny of the hypersensitivity
      vasculitis.

PMID- 9562659
TI  - Mixtard 30 HM Penfill insulin treatment in selected young insulin-dependent
      diabetes mellitus patients. Romanian Young Diabetics Study Team (RYDST).
AB  - Twelve Romanian centers investigated the validity of a two daily insulin regimen
      using premixed biosynthetic human insulin Mixtard 30 HM Penfill (ratio: 30%
      rapid, 70% intermediate NPH-insulin) injected by NovoPen II in IDDM patients.
      Duration of the study was 16 weeks. A total of 159 patients aged 6 to 18 years
      were analyzed. Before study started, patients were educated about diabetes
      management and received strips for home blood glucose monitoring. After a 4-week
      run-in period on previous treatment (mainly two daily injections of self-mixed
      highly purified monocomponent porcine or human insulin given by conventional
      syringes), patients were transferred to two daily injections of Mixtard 30 HM
      Penfill insulin administered by NovoPen II. From transfer to study end (12 weeks)
      total daily insulin dose (mean +/- SD: 32.6 +/- 12.1 vs 33.9 +/- 12.2 IU)
      increased (p < 0.001), four-point blood glucose mean values decreased as well as
      HbA1 (11.4 +/- 2.2% vs 10.5 +/- 2.2%, p < 0.001), without a significant increase
      in the number of hypoglycemic events. NovoPen II was well accepted and preferred
      by patients. Achieved results might be ascribed to the use of Mixtard 30 HM
      Penfill treatment as well as to blood glucose monitoring and a better education.
      Follow-up measurement of HbA1 one year after transfer showed no statistically
      significant differences as compared to the values measured at the end of the
      study.

PMID- 9562658
TI  - Importance of reactive oxygen species in rheumatoid arthritis.
AB  - Free radical oxidation--peroxidation products, superoxide dismutase (SOD)
      activity--and nonproteic thiols were measured in blood from 10 normal subjects
      and 10 patients with rheumatoid arthritis (RA). Peroxidation products and SOD
      activity have been found significantly elevated, while blood nonproteic thiols
      have been found significantly lower in RA patients, as compared to normal
      controls. Also, plasmatic concentration of ceruloplasmin has been found
      significantly higher in RA patients than in controls.

PMID- 9562660
TI  - Malignant histiocytic lymphoma with large lacunar cells.
AB  - A case of lymph node biopsy with a peculiar histological aspect is described. The
      clinical data suggest a malignant lymphoid disease. The histological picture is
      that of a malignant histiocytosis but, among the majority of small histiocytes,
      there are some large cells like the large lacunar cells from Hodgkin's disease.
      These large cells (and some small cells) contain the CD 30 antigen of Reed
      Sternberg cells. It is discussed whether the appropriate diagnosis is Hodgkin's
      disease, malignant histiocytosis, or non-Hodgkin's malignant lymphoma. Our
      diagnosis is Hodgkin's disease, the nodular sclerosing form.

PMID- 9562661
TI  - Statistical analysis for dependent dichotomous data.
AB  - The analysis of means for attributes data (ANOMAD) is used--when normal
      approximation applies to binomial distribution--by extending the analysis of
      means (ANOM) introduced by Ott and Schilling. ANOMAD compares the individual
      proportions or dependent percentages or set of frequencies of subjects responding
      to different stimuli, with the grand average of the proportions. It is
      interesting to see if all temporal values of some risk factors in cardiovascular
      diseases (CD)--acting as "stimuli"--can provide the same effect on a group of
      subjects by emphasizing the most important ones.

PMID- 9562662
TI  - Permeafix: a useful tool to detect antigens and DNA in flow cytometry.
AB  - A new product called Permeafix has been developed for gentle fixation of cells
      and permeability of their membranes. This product is useful for the staining of
      intracellular antigens and parallel quantification of DNA content simultaneously
      with cell surface staining.

PMID- 9562663
TI  - Approach to peripheral neuropathy and neuronopathy.
AB  - Neuropathic disorders encompass those that affect the neuron's cell body or
      neuropathies, those affecting the peripheral process, or peripheral neuropathies.
      The peripheral neuropathies can be broadly subdivided into the myelinopathies and
      axonopathies. These conditions can be hereditary or acquired. Each of these
      disorders has distinct clinical features that enable neurologists to recognize
      the various patterns of presentation. Once a particular pattern is established,
      further laboratory studies including electrophysiologic testing, nerve biopsy,
      and blood and cerebrospinal fluid examination can be performed to confirm the
      clinical impression. Therapy is available in some to correct the underlying
      disease state or at least to improve symptoms.

PMID- 9562664
TI  - Spinal muscular atrophy.
AB  - The history of the spinal muscular atrophies (SMA) began in the 1890s with Guido
      Werdnig and Johann Hoffmann. Together, their papers present a rather complete
      picture of the clinical and pathologic aspects of infantile SMA: onset during the
      first year of life, occurrence in siblings with normal parents, progressive
      floppiness and weakness, hand tremor, and death from pneumonia in early
      childhood. Based on the work of an international collaboration, the following is
      current nomenclature: SMA type 1 (or I) for onset of symptoms before age 6
      months, SMA type 2 (II) for onset between 6 and 18 months, and SMA type 3 (III)
      for onset after age 18 months. Linkage of autosomal recessive SMA to chromosome
      5q11.2-13.3 was reported by Gilliam et al in 1990. A novel gene, whose function
      remains unknown, called the survival motor neuron gene (SMN) at 5q13, contains
      deletions in more than 98% of SMA patients. Some patients with atypical forms of
      SMA have been shown to have mutations in SMN. Because there is no effective
      therapy for SMA, management consists of preventing or treating the complications
      of severe weakness, such as restrictive lung disease, poor nutrition, orthopedic
      deformities, immobility, and psychosocial problems.

PMID- 9562665
TI  - Amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with evidence of
      both anterior horn cell and corticospinal tract degeneration. The incidence of
      ALS is 1 to 2.5 cases per 100,000 population and the disease occurs primarily in
      adult life. The etiology of sporadic ALS remains unknown, although 5 to 10% of
      cases are familial. The diagnosis of ALS requires the presence of both upper and
      lower motor neuron findings and progressive motor dysfunction. Several theories
      regarding the pathogenesis of ALS have emerged including glutamate
      excitotoxicity, free radical oxidative stress, neurofilament accumulation, and
      autoimmunity. Clinical trials involving antiglutamate agents, antioxidants,
      immunosuppressants, and growth factors have shown no substantial benefit in
      slowing progression, with death usually occurring 2 to 5 years following the
      onset of symptoms. The management of ALS patients requires a multidisciplinary
      team that can provide the numerous medical and physical interventions necessary
      to treat weakness and fatigue, bulbar dysfunction, spasticity and pain,
      depression, and respiratory failure.

PMID- 9562666
TI  - Charcot-Marie-Tooth neuropathies and related disorders.
AB  - As a group, the Charcot-Marie-Tooth (CMT) neuropathies represent the most common
      inherited peripheral nerve diseases. Estimates of the prevalence rate are 1 in
      2500 but the exact numbers are difficult to ascertain because of the
      heterogeneity of the syndrome(s). The classification of CMT has undergone change
      coincident with chromosomal localization and gene identification. Table 1
      summarizes the diseases and genetic defects discussed in this review.

PMID- 9562667
TI  - Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy.
AB  - Acute and chronic inflammatory demyelinating polyneuropathies represent an
      important group of disorders. Although the acute form is more common, all
      clinical neurologists will eventually encounter patients with these disorders.
      Acute inflammatory demyelinating polyneuropathy, or Guillain-Barre syndrome, is
      the most common cause of acute generalized weakness. Chronic inflammatory
      demyelinating polyneuropathy, characterized by progressive or relapsing weakness,
      is important to recognize because it represents a significant number of all
      initially undiagnosed acquired neuropathies. There are a variety of reasonable
      therapies available for both of these acquired demyelinating neuropathies.
      Recently much has been learned about pathogenesis and treatment. This review
      describes the clinical presentations, laboratory studies, diagnostic criteria,
      treatment, and prognosis for each disorder.

PMID- 9562668
TI  - Neuropathies associated with connective tissue disease.
AB  - Neuropathies are a common neurologic manifestation of diffuse connective tissue
      disease. Vasculitic neuropathy requires prompt diagnosis and treatment to improve
      its outcome. It is commonly multifocal but may be confluent and symmetrical.
      Vasculitic neuropathy needs to be distinguished from the more common syndromes of
      compression neuropathy, which may also be multifocal, and nonvasculitic distal
      axonal polyneuropathy. Sensory neuronopathy is a distinctive syndrome unique to
      Sjogren's syndrome among the connective tissue diseases. Trigeminal sensory
      neuropathy may be the presenting feature of systemic sclerosis or may develop
      during the course of other connective tissue diseases. This article reviews the
      clinical and diagnostic features of neuropathies associated with the common
      diffuse connective tissue diseases.

PMID- 9562669
TI  - Multifocal motor neuropathy.
AB  - Multifocal motor demyelinating neuropathy is an acquired immune-mediated
      neuropathy with distinctive clinical and electrophysiologic manifestations, and
      response to treatment. Clinically, it is characterized by slowly progressive
      asymmetrical predominantly distal weakness; unilateral wrist drop, grip weakness,
      and foot drop are the commonest initial manifestations. Electrophysiologic
      testing reveals multifocal motor demyelinating features. Persistent, localized,
      partial motor conduction block is the hallmark of the disorder. Results of
      sensory nerve conduction studies are generally normal, consistent with the lack
      of sensory symptoms and signs. Most patients show marked improvement in strength
      after treatment with intravenous human immunoglobulin or cyclophosphamide. The
      pathogenesis of the disease is not completely understood. An autoimmune
      pathogenesis is considered likely based on the beneficial response to
      immunomodulatory treatment and the presence of serum anti-GM1 ganglioside
      antibodies in affected patients.

PMID- 9562670
TI  - Autoantibody testing in the evaluation of peripheral neuropathy.
AB  - A recent development in the evaluation of peripheral neuropathy patients has been
      the identification of autoantibodies directed against various peripheral nerve
      antigens. For some conditions, assay for the antibodies can be very helpful in
      confirming a diagnosis. In others, an antibody may be associated with clinical
      findings that are neither distinctive nor specific, and the role of the antibody
      in the pathogenesis of the clinical disease may remain uncertain. The appropriate
      use of antibody assays in clinical diagnosis and management is therefore often
      unclear. This article highlights the historical background for the best-described
      "antinerve" antibodies, and reviews the biochemistry, immunology,
      pathophysiology, and treatment implications of the associated clinical
      conditions.

PMID- 9562671
TI  - Diabetic peripheral neuropathy.
AB  - Diabetes mellitus leads to several recognizable clinicopathologic neuropathic
      syndromes. Diagnosis and evaluation requires a thorough history and neurologic
      examination, nerve conductions and needle electromyography (EMG), blood studies,
      consideration of cerebrospinal fluid analysis, and nerve and muscle biopsy in the
      most severely affected patients. Microangiopathy is the commonest cause of
      diabetic neuropathy, associated with potentially reversible metabolic,
      immunologic, or ischemic injury. Tight glycemic control and symptomatic therapy
      is beneficial in some patients but does not prevent progression of neuropathy
      especially in patients with severe motor and gait disability. Intravenous immune
      globulin is a novel therapy in diabetic patients. It may be considered in
      selected patients well characterized by clinical, electrophysiologic,
      histopathologic studies, and one of the following progressive syndromes:
      mononeuropathy multiplex, primary demyelinating motor or sensorimotor neuropathy,
      and peripheral nerve perivasculitis or microvasculitis associated with vascular
      membrane attack complex protein deposits.

PMID- 9562672
TI  - Cryptogenic sensory and sensorimotor polyneuropathies.
AB  - Chronic sensory or sensorimotor polyneuropathy is a common clinical problem
      referred to neurologists. Even with modern diagnostic approaches, up to one-third
      of them will remain unclassified. Recent studies have provided insight into their
      clinical spectrum and course. The age of onset tends to be in the sixth to
      seventh decade of life. Symptoms progress slowly, and most patients present with
      paresthesias or pain. Cryptogenic polyneuropathies are almost exclusively axonal
      on clinical, electrophysiologic, and histologic grounds. Overall, the prognosis
      is favorable, and only a small minority of patients develop significant motor
      disability or physical incapacitation. Progression to a nonambulatory state
      essentially never occurs. Successful management should focus on rational
      pharmacotherapy for painful paresthesias combined with patient education and
      reassurance.

PMID- 9562673
TI  - Leprous neuropathy: an American perspective.
AB  - Although its overall prevalence is decreasing, leprosy continues to be a major
      cause of neuropathy worldwide. In the United States, it is a relatively rare
      condition. As a result, physicians may lack familiarity with the disease, which
      can delay diagnosis and treatment. Leprous neuropathy is characterized by
      involvement of dermal nerves and superficial peripheral nerve trunks in cooler
      body regions. A continuing pattern of immigration from endemic areas may allow
      practicing neurologists in any region of the country to become involved in the
      care of patients with leprosy. The diagnosis should be considered in patients
      from endemic regions presenting with peripheral neuropathy with or without skin
      lesions. Readily available diagnostic testing, access to subspecialists, and
      modern transportation and information systems through the satellite clinics of
      the Hansen's Disease center serve as major advantages for the management of
      leprosy patients in the United States.

PMID- 9562674
TI  - Neuropathies associated with malignancy.
AB  - Patients with malignancy can develop peripheral neuropathies as (1) a direct
      effect of the cancer by invasion or compression of nerves, (2) a remote or
      paraneoplastic effect, or (3) an iatrogenic effect of treatment. Focal or
      multifocal cranial neuropathies, radiculopathies, and plexopathies typically
      result from tumor infiltration, herpes zoster infection, or radiation-induced
      injury. Sensorimotor polyneuropathies are the most frequently encountered
      peripheral nerve syndromes, but motor neuropathies, sensory neuronopathies,
      polyradiculoneuropathies, and autonomic neuropathies can also occur. Although
      uncommon, paraneoplastic mechanisms should be considered in a patient with
      malignancy and an associated peripheral nerve disorder, especially in the setting
      of small-cell lung cancer or lymphoproliferative cancer. Toxic neuropathies occur
      with exposure to several chemotherapeutic agents, including the vinca alkaloids,
      cisplatin, taxanes, and suramin. These neuropathies are usually dose-related,
      sensory-predominant, and at least partially reversible, with an axonopathic or
      ganglionopathic mechanism. Suramin is unique in causing subacute, demyelinating
      polyradiculoneuropathy.

PMID- 9562675
TI  - Nerve models, role models, reminiscences, and a tribute to Robert E. Lovelace,
      M.D., F.R.C.P.

PMID- 9562677
TI  - Associated malformations in infants and fetuses with upper or lower neural tube
      defects.
AB  - The paper describes associated malformations in infants born with neural tube
      defects (N = 3,809) from three large malformation registers and in fetuses
      aborted because of a diagnosed neural tube defect (N = 748) from two of the
      registers. In infants, upper spina bifida and encephalocele are more often
      associated with non-neural malformations than anencephaly or lower spina bifida.
      Aborted fetuses with spina bifida or encephalocele have associated malformations
      registered more often than infants with those neural tube defects, but the
      opposite is true for anencephaly. The degree of detail of the investigation of an
      aborted specimen or a perinatally dead infant will contribute to such differences
      but they can also depend on the fact that prenatal detection may be facilitated
      by the simultaneous presence of other malformations like body wall defects. Also,
      fetuses with many malformations may be more prone to abort spontaneously late in
      pregnancy. Variable prenatal diagnosis may, therefore, explain population
      differences in the pattern of associated malformations. The type of associated
      malformation differs with the level of the neural tube defect: this could be due
      to different causal mechanisms or be a question of cranio-caudal level and/or
      timing. For limb reduction defects, however, we did not find any association
      between upper limb and upper neural tube defects or lower limb and lower neural
      tube defects. These findings together with other epidemiological data support the
      idea that upper and lower neural tube defects may have different significance in
      epidemiological studies and should be treated separately.

PMID- 9562676
TI  - Adult and two children with fetal methotrexate syndrome.
AB  - The folic acid antagonists, methotrexate and aminopterin, are known to be
      teratogenic in humans. The critical period for their teratogenecity is suspected
      to be between 6 to 8 weeks post-conception. Fetal exposure from 10 to 32 weeks
      weeks post-conception to methotrexate alone or in combination with other anti
      cancer drugs has not resulted in obvious teratogenic effects. Methotrexate is
      often used to treat cancers but is occasionally used as an abortifacient. The
      long-term outcome of the fetal aminopterin syndrome has been published in only
      four adults. We report on a 28-year-old man with fetal methotrexate syndrome and
      two children with mild manifestations of the syndrome. One child was
      inadvertently exposed to methotrexate from 7 1/2 through 30 weeks post-conception
      because his mother was receiving it for treatment of breast cancer. The other was
      exposed from 11 weeks and 5 days through 25 weeks in an attempt to induce
      abortion. The 28-year-old man has craniofacial and digital anomalies, growth
      retardation but normal intelligence as noted in the previously reported cases.
      These cases remind us of the teratogenicity of methotrexate and should serve as a
      warning that if methotrexate is used as an abortifaciant and an abortion does not
      ensue, there is a teratogenic risk.

PMID- 9562678
TI  - Unilateral suprainguinal ectopic scrotum: the role of the gubernaculum in the
      formation of an ectopic scrotum.
AB  - A rare case of ectopic scrotum is described together with a review of the
      literature and a discussion of the embryological role of the gubernaculum in the
      formation and location of normal and ectopic scrota. We identified 16 reported
      cases of a suprainguinal ectopic scrotum, 4 cases of a femoral ectopic scrotum,
      26 cases of penoscrotal transposition, and 19 cases of a perineal (accessory)
      scrotum. Although the gubernaculum is a prerequisite for the ultimate location of
      both the testis and scrotum, its role is complicated by the subsequent
      differential growth of the labioscrotal folds in which the gubernaculum is
      stabilized. If this interaction is disturbed, the result may be a suprainguinal
      ectopia, penoscrotal transposition or a perineal scrotum. A femoral ectopic
      scrotum, unlike the above, is the result of an aberrant gubernacular
      stabilization. While the etiology of these malformations is likely to be
      multifactorial, the existence of an inbred strain of rats characterized by a high
      incidence of an ectopic scrotum suggests a genetic component to this anomaly.

PMID- 9562679
TI  - Normal and abnormal embryonic development of the anorectum in human embryos.
AB  - In the literature, some controversy still exists about the normal and abnormal
      development of the human anorectum. Therefore, a three-dimensional and
      histological study was performed on human embryos. In early anorectal development
      (< or = 49 days postfertilization), the cloaca plays a crucial role, separated
      from the amniotic cavity by its cloacal membrane. In the cloaca, the yolk
      sac/primitive hindgut and allantois/primitive urogenital sinus enter. During the
      embryonic caudal folding process, incorporation of these structures occurs,
      including their surrounding extraembryonic mesoderm, which fuses to form the
      urorectal septum. Consequently, this septum does not grow in the direction of the
      cloacal membrane, and fusion of these structures is likewise never observed. The
      cloaca remains as such until the cloacal membrane ruptures by apoptotic cell
      death. The dorsal part of the cloaca then becomes part of the amniotic cavity,
      and is by no means involved in the development of the anorectum. The tip of the
      urorectal septum will become the perineal area. Soon after rupture of the cloacal
      membrane, during late anorectal development (> or = 49 days postfertilization), a
      secondary occlusion of the anorectal canal occurs, first due to adhesion,
      followed by formation of an epithelial "plug" at the level of the anal orifice.
      Recanalization, by apoptotic cell death, of this secondary occluded anal orifice
      occurs later during development. Based on these embryological observations,
      congenital anorectal malformations with an abnormal communication to the exterior
      are best explained as early embryonic defects. The abnormal communications,
      usually called fistulae, should be regarded as ectopic anal orifices. Anorectal
      malformations with the anus in normal position are best explained as late
      embryonic defects.

PMID- 9562680
TI  - Dietary myo-inositol therapy in hyperglycemia-induced embryopathy.
AB  - Dysmorphogenesis in diabetic mothers occurs more frequently than in the general
      population. This phenomenon is believed to be caused by the teratogenic effects
      of metabolic fuel mixtures with associated membrane injury and aberrations in the
      biochemical constituents. The present experiment was designed to determine: 1) if
      hyperglycemia-induced membrane injury is associated with intracellular and/or
      extracellular lipid disturbances; 2) if supplemental myo-inositol therapy
      prevents hyperglycemia-induced embryopathy; 3) if a correlation exists between
      dietary myo-inositol, serum and tissue levels of myo-inositol, and conceptus
      development; and 4) the cellular content of arachidonic acid following myo
      inositol supplementation. Sixty-five female Sprague-Dawley rats were mated, and
      divided into three groups. One group was nondiabetic normal controls, and two
      groups had diabetes experimentally induced with streptozotocin. Of the diabetic
      groups, one received a normal diet, while the other received a myo-inositol
      supplemented diet during the period of organogenesis. Blood samples were
      collected on days 0 and 12 of pregnancy. Embryos and yolk sacs were analyzed for
      myo-inositol and arachidonic acid levels, using mass spectrochromatography.
      Dietary myo-inositol supplementation of diabetic mothers resulted in a
      significant decrease in the incidence of neural tube defects when compared with
      diabetics not receiving supplements (9.5 vs. 20.4%; P < 0.05). This protective
      effect was incomplete, based on the incidence observed in the nondiabetic
      controls (9.5 vs. 3.8%; P < 0.05). The myo-inositol embryonic tissue levels in
      the diabetic group which had been fed a regular diet without supplementation were
      significantly lower than in the nondiabetic group. Dietary therapy successfully
      restored myo-inositol levels in the yolk sacs, as suggested by similar tissue
      levels in diabetics receiving myo-inositol supplementation and normal controls
      (18.7 +/- 1.3 vs. 19.1 +/- 2.0 ng/mg; P = ns). Dietary therapy, however, failed
      to restore myo-inositol levels in the embryos, suggesting hyperglycemia-induced
      faulty transport of nutrients from the yolk sac to the embryo. No correlation was
      noted between maternal blood levels of myo-inositol, with or without
      supplementation, and the clinical outcome. Tissue arachidonic acid levels were
      markedly reduced in the conceptuses of diabetic mothers with (0.4 +/- 0.1
      micrograms/mg) or without (0.25 +/- 0.08 micrograms/mg) myo-inositol
      supplementation when compared to the nondiabetic controls (3.33 +/- 0.24
      micrograms/mg). These data demonstrate that diabetes-induced embryopathy is
      associated with a deficiency state in both myo-inositol and arachidonic acid. The
      myo-inositol deficiency is not demonstrated at the serum level, but rather at the
      tissue level, suggesting a paracrine action. Dietary supplementation of myo
      inositol is associated with an increase in tissue myo-inositol levels and a
      decrease in malformations. This therapy holds promise for use as a dietary
      prophylaxis against diabetic embryopathy.

PMID- 9562681
TI  - Comparison of lectin binding patterns in malformed and normal human embryos and
      fetuses.
AB  - Altered glycosylation in the course of disease detectable by changes in lectin
      binding patterns has been well established for adult tissues, but only a few
      authors have described carbohydrate entities during normal human embryonic and
      fetal development. Whether alterations in carbohydrate patterns occur in human
      embryonic and fetal tissues, affected by malformations, remains to be
      investigated. We, therefore, examined human embryos and fetuses at corresponding
      developmental stages with and without malformations (spina bifida, exencephaly,
      cleft lip and cleft palate, and dysmelia) with respect to their lectin binding
      patterns for the lectins RCA I, PNA, WGA, SBA, SNA, Con A, and LTA. Our results
      demonstrated that during the development of malformations, the affected tissue
      sites exhibited a different carbohydrate pattern from normally developed
      specimens. Furthermore, tissues known to be sites of secondary malformation,
      accompanying the primary defect, although displaying a histologically normal
      appearance, also showed an altered carbohydrate pattern. This might indicate a
      possible general alteration in the carbohydrate pattern in the course of
      development of malformations in man.

PMID- 9562682
TI  - Seasonal variation in birth date of children with cleft lip.
AB  - Liability to neural tube defects is increased by maternal dietary deficiency, and
      children with neural tube defects show a possibly related seasonal variation in
      date of birth. Since maternal dietary insufficiency may also increase liability
      to cleft lip, with or without cleft palate (CLP), we wondered if children with
      CLP would also show a seasonal variation in birth date. The multifactorial
      threshold model predicts that any such effect would be more apparent in males
      than females, since CLP is more frequent in males. Month of birth was obtained
      from records of 598 children with CLP seen at The Montreal Children's Hospital
      between 1950 and 1996. Children with syndromes or associated malformations were
      excluded. There was a significant tendency for children with CLP to be born more
      often in the summer than in winter. The difference was greater in males than in
      females. The seasonal fluctuation in month of birth of children with CLP is
      consistent with the presence of an environmental factor increasing liability,
      with a maximal effect in November-December. This might be related, at least in
      part, to a seasonal fluctuation in maternal nutrition. The data support the
      prediction that analyzing the data for the sexes separately would amplify the
      effects of variation in liability for a multifactorial threshold trait that has a
      different frequency in males and females. This approach could be useful in the
      study of other gene-environment interactions.

PMID- 9562683
TI  - Field evaluation of two bait delivery systems for the oral immunization of dogs
      against rabies in Tunisia.
AB  - Two bait delivery systems for the oral immunization of dogs against rabies were
      tested in small scale field trials in a semi-rural area in Tunisia: bait delivery
      to owned dogs during door to door visits of households (door to door baiting) and
      distribution of baits on transect lines (transect line baiting). A prototype bait
      (DBL2) configured for industrial production and containing either
      sulfadimethoxine (SDM) as a systemic marker or Rhodamine B as a topical marker
      was used. The overall proportion of dogs which took a bait and presented topical
      marker staining after door to door baiting was 59.1%. The total time and costs
      spent per bait accepting dog averaged 34 person minutes and US$4, respectively.
      Unconsummated baits were readily recovered. No unprotected human contacts with
      baits were recorded. Door to door baiting is a very specific but time-consuming
      method that enables a safe administration of vaccine baits to owned dogs. For
      transect line baiting, baits were distributed at a density of ca 3000 baits per
      km2 along double transect lines. Baits were recovered after 20 h. According to
      the proportion of SDM positive serum samples, 24.1% of owned dogs in the baiting
      area had consumed baits. Of all owned and ownerless dogs, presumably free-roaming
      during transect line baiting, > 40% had consumed baits. The total time and costs
      spent per bait accepting dog averaged 48 person minutes and ca US$20,
      respectively. The household census revealed 32 direct human contacts with the
      bait matrix which corresponds to 1.4% of inhabitants. Placing baits on transect
      lines gives the possibility to vaccinate dogs not accessible by vaccination
      systems which base on dog owner participation. However, the method is not
      specific, less safe than other systems, not easily accepted by the human
      population, and costly.

PMID- 9562684
TI  - The effect of pertussis toxin and whole-cell pertussis vaccine on haemodynamics
      and autonomic responsiveness in the rat depends on route of administration and
      age.
AB  - Vaccination of children with Diphtheria, Tetanus, Poliomyelitis and pertussis
      vaccine (DTPoP-vaccine) containing the whole-cell pertussis component is known to
      be associated with manifestation of side-effects such as acute encephalopathy,
      convulsions and hypotensive-hyporesponsive episodes. In young and adult rats the
      effects of pertussis toxin and DTPoP-vaccine on haemodynamics and autonomic
      responsiveness are evaluated following treatment with high dose via different
      routes of administration (s.c., i.p. and i.v.). The effect of pertussis toxin is
      dose-dependent (between 1 and 20 micrograms kg-1) and largest responses are
      observed after i.v. administration. At 20 micrograms kg-1, i.v. pertussis toxin
      decreases baseline diastolic blood pressure and increases baseline heart rate by
      31% and inhibits autonomic responsiveness (salbutamol-induced increase in
      diastolic blood pressure and arecoline-induced decrease in heart rate). In adult
      rats DTPoP-vaccine induces generally more prominent effects than in young rats.
      In adult rats DTPoP-vaccine reduces baseline diastolic blood pressure by 25%
      while no response is observed in young rats. In adult rats DTPoP inhibits the
      adrenergic response though less compared to treatment of pertussis toxin. After
      treatment with DTPoP-vaccine (single or twice) only minor differences are
      observed between young and adult rats. Present results show that adult rats are
      more sensitive to pertussis toxin and pertussis vaccine than young rats and that
      the responses depend on the route of administration.

PMID- 9562685
TI  - Relationship between structure and neutralizing activity of rabbit tetanus
      antibodies elicited by acellular and whole-cell pertussis DTP vaccines.
AB  - Symmetric and asymmetric IgGs having different neutralizing capacity are
      synthesized in variable proportions by the same clones during the course of
      immune response. The neutralizing activity of tetanus antibodies was studied in
      rabbits vaccinated with acellular (DTPa) or whole-cell pertussis (DTPw) vaccines.
      Symmetric and asymmetric F(ab)'2 fragments from the IgG fraction of the peak
      serum pools from each group of rabbits were purified by concanavalin A
      chromatography and measured by ELISA. After the third vaccine dose the asymmetric
      antibody percentage for DTPw (40%) was twice that for DTPa (20%). The
      neutralizing activity of asymmetric antibodies was roughly sixfold lower than
      symmetric ones. When antibody values titrated by ELISA approach minimal
      protective level, the proportion of symmetric antibodies with high toxin
      neutralizing activity acquires crucial importance.

PMID- 9562687
TI  - Mucosal immunogenicity elicited in mice by oral vaccination with
      phosphorylcholine encapsulated in poly (D,L-lactide-co-glycolide) microspheres.
AB  - Poly(D,L-lactide-co-glycolide) microspheres loaded with phosphorylcholine linked
      to thyroglobulin (PC-Thyr) as protein carrier were prepared. The entrapment
      efficiency reached 80% when the initial protein:polymer ratio was 1:8. Ninety
      four percent of the loaded microspheres had a diameter < or = 10 microns. The
      encapsulation process did not alter PC-Thyr absorbance nor PC antigenic
      reactivity. Oral administration of these microspheres induced a specific IgA
      response in intestinal, pulmonary and vaginal secretions, as well as a strong
      specific systemic immune response in female Balb/c mice. This suggests the need
      to explore further the potential ability of PC-Thyr loaded microspheres to
      protect against infections caused by PC-bearing microorganisms which invade or
      colonize different mucosal sites.

PMID- 9562686
TI  - Immunogenicity of liposome-associated and refined antigen oral cholera vaccines
      in Thai volunteers.
AB  - A mixture of Vibrio cholerae antigens made up of crude fimbrial extract,
      lipopolysaccharide and procholeragenoid was administered orally to Thai
      volunteers either as free antigen or associated with liposomes. All vaccines and
      controls were administered in three doses given at 14 day intervals. Nine
      volunteers received liposome-associated vaccine and seven received free vaccine.
      Liposomes without antigens were given to eight volunteers and seven volunteers
      received 5% NaHCO3 solution alone. Both vaccines had 100% immunogenicity as
      determined by serum vibriocidal antibody responses. Liposomes were shown by
      indirect ELISA to localize the immune response against lipopolysaccharide and
      fimbriae to the intestinal mucosa. Vaccines given liposome-associated antigens
      had a higher rate of antigen-specific antibody response than did individuals who
      had received free antigens. The vaccines induced intestinal antibodies of IgM
      and/or IgA isotypes, but not IgG antibody.

PMID- 9562688
TI  - Identification of potential CD8+ T-cell epitopes of the 19 kDa and AhpC proteins
      from Mycobacterium tuberculosis. No evidence for CD8+ T-cell priming against the
      identified peptides after DNA-vaccination of mice.
AB  - Mycobacterium tuberculosis is one of the major killers among infectious agents.
      It is of great importance to develop an efficient vaccine against M. tuberculosis
      since the only available vaccine, M. bovis-BCG, has a low efficacy. Furthermore,
      the emergence of multi-drug-resistant M. tuberculosis strains makes it difficult
      to cure the disease. CD8+ T cells have been implied to play an important role in
      protective immunity against M. tuberculosis. A good vaccination strategy for the
      induction of cytotoxic CD8+ T-cell responses is naked DNA-injection of eukaryotic
      expression vectors. The use of DNA-injection in an attempt to induce cytotoxic
      CD8+ T-cell responses against epitopes of the 19 kDa or AhpC proteins from M.
      tuberculosis in mice was studied. MHC class I binding assays, of peptides derived
      from these proteins, demonstrated the presence of potential CD8+ T-cell epitopes.
      However, CD8+ T-cell responses against the peptides after DNA-injection were not
      detected. Furthermore, no difference in the kinetics of bacterial clearance was
      observed in vaccinated versus unvaccinated animals, even though 19 kDa and AhpC
      specific antibodies were readily detected in the serum of vaccinated animals.
      Taken together these results suggest that the 19 kDa and AhpC genes are not good
      candidates for DNA vaccines against M. tuberculosis.

PMID- 9562689
TI  - Intra nasal administration of poly-lactic acid microsphere co-encapsulated
      Yersinia pestis subunits confers protection from pneumonic plague in the mouse.
AB  - Equivocal doses of soluble, or high molecular weight poly (lactic acid)
      microsphere co-encapsulated, F1 and V subunit antigens of Yersinia pestis were
      used to immunize mice intra-nasally. Animals were dosed on day 1 and 7 with 2.724
      micrograms V plus 0.956 micrograms F1. Co-encapsulated antigens induced superior
      systemic and mucosal immunity in comparison with free F1 and V. All of the mice
      immunized with soluble antigens died shortly after an aerosol challenge
      consisting of 1 x 10(5) colony-forming units of plague bacteria. In contrast, 66%
      of the co-encapsulated subunit vaccinees survived this lethal challenge. Humoral
      immunity to plague was improved further, resulting in 80% protection from
      challenge, if a relatively high dose (10 micrograms) of cholera toxin B subunit
      was added to the microsphere suspension prior to intra-nasal delivery.
      Significantly, by adding 10 micrograms cholera toxin B subunit to the free
      antigen solution, a 100% post-challenge survival rate was attained. We conclude
      that in this animal model of pneumonic plague, intra-nasal administration of
      microgram quantities of Yersinia pestis subunits confers protective immunity,
      provided the vaccines are microencapsulated or admixed with a strong mucosal
      adjuvant, such as the cholera toxin B subunit.

PMID- 9562691
TI  - Apoptosis in asymptomatic HIV-1 seropositives immunized with HIV-1 env
      glycoprotein (gp160): effects of administration of Zidovudine in vivo and
      interleukin-2 in vitro.
AB  - In this paper we report the effects of VaxSyn (Protein Sciences Corp.)
      immunization on spontaneous apoptosis occurring in vitro after culture of PBMC in
      medium alone in 30 HIV-seropositive patients enrolled in a double-blind clinical
      trial that included three groups: treatment with VaxSyn, AZT and VaxSyn, and AZT.
      Our data show no significant modifications in the levels of apoptosis observed in
      the three groups over the long-term follow-up (up to 720 days). This was not
      associated with any significant modifications in other clinical or immunological
      features. However, analysis of apoptosis performed shortly after the first
      immunization (at days 3 and 7) showed a significant reduction in the rate of
      apoptosis in patients receiving AZT and AZT and VaxSyn, as compared with patients
      receiving VaxSyn alone (30.42 +/- 2.52 SE at day 0 and 23.74 +/- 1.84 at day 3; p
      = 0.039). Our data also indicate that addition of IL-2 in vitro had a significant
      inhibitory effect on mortality in all the randomization groups, especially in
      those receiving AZT (alone or in combination with VaxSyn).

PMID- 9562690
TI  - Safety and immunogenicity of a hepatitis B vaccine formulated with a novel
      adjuvant system.
AB  - A formulation of recombinant hepatitis B surface antigen (HBsAg) combined with a
      novel adjuvant system, SBAS4--a combination of aluminium salt and monophosphoryl
      lipid A (MPL), was assessed in 27 healthy adult volunteers with a commercial
      vaccine (Engerix-B) as control. After three doses (0, 1, 6 months schedule),
      reactogenicity profiles were similar. Local reactions were essentially mild, the
      most frequent being soreness at the injection site. Seroprotection was achieved
      after two doses in all subjects given the candidate vaccine, all Engerix-B
      vaccines being seroprotected after the third dose. After the second and third
      doses, higher anti-HBs Geometric Mean Titres (GMTs) were observed in the group
      which received the formulation with the novel adjuvant system, and cellular
      immunity, measured as HBsAg-specific lymphoproliferation was stronger than with
      Engerix-B. These results indicate that the new formulation is safe, well
      tolerated and immunogenic and may promote more rapid protection against hepatitis
      B infection.

PMID- 9562692
TI  - Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis
      hepatitis B vaccine administered according to two different primary vaccination
      schedules. Multicenter Working Group.
AB  - The reactogenicity and immunogenicity of a tetravalent diphtheria-tetanus
      acellular pertussis-hepatitis B (DTPa-HB) vaccine (SmithKline Beecham) were
      studied in 565 infants immunized according to one of two different schedules, at
      2, 4 and 6 months of age (group A n = 208) or at 3, 5 and 11 months of age (group
      B n = 357). The incidences of local and general reactions within the first 8 days
      after vaccination were similar in the two groups of infants, the vast majority
      being mild in intensity and occurring within 2-3 days of vaccine administration.
      Severe local symptoms were rare: pain after 0.6% of all doses, redness after 0.5%
      and 1.3%, and swelling after 0.3% and 1.5%, in group A and B, respectively. Only
      one infant in group A and one in group B had a temperature > 39.0 degrees C. Both
      schedules proved satisfactory in obtaining high levels of antibodies against all
      antigens. The rates of serologic response against the different antigens reached
      100% in both groups. Antibody titres against all vaccine components were elevated
      following both schedules, but after the third dose of vaccine geometric mean
      antibody titres (GMTs) against D toxoid, filamentous haemagglutinin (FHA),
      pertactin (PRN) and hepatitis B (HB) were significantly higher in the 3, 5, 11
      group than after the 2, 4, 6 schedule. Antibody titres measured at 7 months of
      age in the group immunized at 2, 4 and 6 months were higher than those reached at
      6 months of age in infants immunized at 3, 5 and 11 months, but FHA and PRN were
      within the range of DTPa vaccine with proven efficacy. We conclude that DTPa-HB
      vaccine was safe, well tolerated and highly immunogenic. Both vaccination
      schedules (2, 4, 6 and 3, 5, 11) can be considered suitable for mass immunization
      programmes.

PMID- 9562693
TI  - Whole-killed gp120-depleted HIV-1 antigen in a murine model for prophylactic
      vaccination.
AB  - In this study, the effects were examined of dose and adjuvant of whole-killed
      gp120-depleted HIV-1 antigen on antibody and cytokine responses in a murine
      model. Immunization with increasing doses of inactivated HIV-1 antigen in
      Incomplete Freund's Adjuvant (IFA) resulted in increased production of IL-4 and
      IgG1 antibody with decreased production of interferon gamma. Immunization with
      inactivated HIV-1 antigen in Detox PC adjuvant produced TH1 type predominant
      cytokine patterns along with IgG2a subclass antibody. Higher levels of interferon
      gamma were associated with immunization with inactivated HIV-1 antigen in Detox
      PC compared with inactivated HIV-1 in IFA or inactivated HIV-1 in saline.
      Inactivated HIV-1 antigen in Detox PC adjuvant produced a trend of lower levels
      of the beta-chemokine MIP-1 alpha compared with inactivated HIV-1 in IFA or
      saline. Dose and adjuvant play an important role in the type of immune response
      elicited to a whole-killed HIV vaccine. Low doses of inactivated HIV-1 antigen in
      Detox PC adjuvant are currently being studied in animal models in order to
      optimize cell-mediated immunity against HIV infection.

PMID- 9562694
TI  - LT(R192G), a non-toxic mutant of the heat-labile enterotoxin of Escherichia coli,
      elicits enhanced humoral and cellular immune responses associated with protection
      against lethal oral challenge with Salmonella spp.
AB  - In the current study we examined the ability of a novel mucosal adjuvant,
      LT(R192G), to enhance the humoral and cellular immune responses against killed
      Salmonella spp. and to affect protection against lethal oral challenge with wild
      type organisms. Mice orally immunized with killed S. dublin in conjunction with
      LT(R192G) were protected against lethal oral challenge and had higher IFN-gamma,
      IL-2 and IgG responses than did mice orally immunized with killed S. dublin alone
      which were not protected. This study demonstrates that the function of LT(R192G)
      in protection against typhoid-like disease is to upregulate/enhance the Th1 arm
      of the immune response against killed organisms. When used as a mucosal adjuvant,
      LT(R192G) enables the use of killed bacteria or viruses as vaccines by enhancing
      the overall humoral and cellular host immune response to these organisms,
      especially the Th1 arm of the immune response. These findings have significant
      implications for vaccine development and further support the potential of
      LT(R192G) to function as a safe, effective adjuvant for mucosally administered
      vaccines.

PMID- 9562695
TI  - Enhancement of immune response to intranasal influenza HA vaccine by
      microparticle resin.
AB  - We evaluated the potential application of ion-exchange resins for the enhancement
      of intranasal immune response to influenza HA vaccine in mice. Female Balb/c mice
      were intranasally immunized with inactivated influenza HA vaccine with one of
      four kinds of resin microparticles: sodium polystyrene sulfonate, calcium
      polystyrene sulfonate, polystyrene benzyltrimetylammonium chloride, or
      polystyrene divinylbenzene. Haemagglutinin-inhibiting antibodies were measured in
      the serum and IgA antibodies in the nasal wash after 4 weeks. The results
      demonstrated that intranasal administration of influenza HA vaccine in
      combination with the 20-45 microns sized particles of sodium polystyrene
      sulfonate resin induced the highest levels of mucosal IgA, and enhanced systemic
      haemagglutinin-inhibiting antibodies. While the Th2-type cytokine IL-4 was
      detected in the sera after intranasal immunization with HA vaccine and sodium
      polystyrene sulfonate, neither IFN-gamma nor IL-2 could be detected. Furthermore,
      mice intranasally immunized with HA vaccine together with sodium polystyrene
      sulfonate resin showed higher protection against viral challenge than those that
      received HA vaccine alone. Intranasal administration of influenza HA vaccine with
      sodium polystyrene sulfonate resin might be both a safe and an effective means of
      immunization.

PMID- 9562696
TI  - Emergency vaccination of pigs against foot-and-mouth disease: protection against
      disease and reduction in contact transmission.
AB  - The protective ability of two novel oil-based FMD vaccines in pigs was examined.
      Both vaccine formulations were shown to protect pigs against airborne challenge
      with homologous FMDV within four days of vaccination, but not at two and three
      days post-vaccination. Protection was associated with the induction of variable
      and low titre serum antibody responses. A transmission study showed that
      protective immunisation resulted in reduced virus excretion. Vaccination at seven
      days, but not at four days, prior to challenge prevented contact transmission of
      FMD. The two formulations tested in this study have the favourable
      characteristics of low viscosity, low reactivity and high potency emergency FMD
      vaccines for use in strategic vaccination campaigns to assist the control of
      outbreaks of FMD.

PMID- 9562697
TI  - Role of long-persisting human hepatitis E virus antibodies in protection.
AB  - The role of long-persisting HEV antibodies in humans was investigated. A well
      characterized human volunteer anti-HEV (IgG) after 4 years of the recovery of the
      disease was passively immunized (200 mg kg-1 body wt) intramuscularly into three
      rhesus monkeys (nos 7, 8 and 9), while two monkeys (nos 5 and 6) were injected
      with normal immunoglobulin preparation (negative for anti-HEV IgG). At 16 h later
      all the animals were challenged intravenously with live HEV, as 10% stool extract
      prepared from the volunteer (positive for HEV by solid-phase immune electron
      microscopy). It was seen that transaminases (ALT/AST) were elevated in immunized
      monkeys on day 49 (no. 8), 60 (no. 7) and 86 (no. 9) after the virus challenge.
      On serological examination, all immunized (nos 7, 8 and 9) and one unimmunized
      (no. 6) monkeys were found positive for HEV IgM on day 10 post-challenge, while
      monkey no. 5 was negative. Further, all the animals from the immunized and
      unimmunized group seroconverted to HEV-IgG when tested on days 25 and 55 post
      challenge. This has clearly shown that there is no protection. Therefore, these
      long-persisting HEV antibodies alone in humans, may not be protective in passive
      immunization.

PMID- 9562698
TI  - The policy of admission to the education in medicine and dentistry in the French
      speaking community of Belgium.

PMID- 9562699
TI  - The policy of admission to the education in medicine and dentistry in the Flemish
      community in Belgium.

PMID- 9562700
TI  - Cellular immunotherapy: a new avenue in internal medicine.

PMID- 9562701
TI  - Chronic aortic dissection masquerading as systemic disease.
AB  - We report two cases of chronic aortic dissection whose prominent features were
      characterized by systemic symptoms (prolonged low grade fever, fatigue, weight
      loss) and biological acute phase response. In the first patient, a surgical
      repair of the descending thoracic aorta aneurysm was performed, allowing the
      disappearance of general manifestations, whereas spontaneous resolution occurred
      in the second case. Although aortic dissection is usually an acute and highly
      symptomatic event, the disorder can present--albeit rarely--as systemic illness
      and fever of unknown origin.

PMID- 9562702
TI  - [Chronic eosinophilic pneumopathy in a black African patient].
AB  - The authors report a case of a black African patient who suffers from a chronic
      eosinophilic pneumonia. In view of the lack of precise reporting in the
      literature of such a case in black Africans, the initial difficulty of strictly
      excluding a parasitologic etiology is discussed. From the comparison of
      paraclinical and clinical data with those of the literature, the authors
      emphasize the close relationship between asthma and chronic eosinophilic
      pneumonia and the role of alveolar eosinophils in the physiopathology of that
      illness.

PMID- 9562703
TI  - A multicentre survey of antimicrobial resistance in gram-negative isolates from
      Belgian intensive care units in 1994-1995. Belgian Multicenter ICU Study Group.
AB  - The aim of this prospective study was to evaluate the distribution and antibiotic
      susceptibility of aerobic Gram-negative bacilli isolated from patients in
      intensive care units in 18 Belgian hospitals during 1994 and 1995. A standardised
      method (i.e. the E-test) was used in each center to determine the minimum
      inhibitory concentrations of 12 major antibiotics against 1435 consecutive, non
      duplicate, Gram-negative isolates (close to 100 strains per hospital) during a
      period of 6 months. The isolates were mainly isolated from the lower respiratory
      tract (57.4%), urinary tract (17.7%), pus (7.9%) or blood specimens (7.8%) and
      were mainly P.aeruginosa (20.3%), E.coli (19.9%) and Enterobacter spp. (12.6%).
      Overall inducible Enterobacteriaceae (IE) accounted for 29.8% of all isolates,
      and E.aerogenes was the most frequently isolated species in this group (27.6%).
      The overall susceptibility rate (all species confounded) was about 70% to
      piperacillin, ticarcillin-clavulanic acid and ceftriaxone, 78% to piperacillin
      tazobactam; 87% both to ceftazidime and to ciprofloxacin; and 90% to imipenem.
      Widespread resistance was observed in several IE species to third generation
      cephalosporins, broad-spectrum penicillins and to ciprofloxacin. By contrast,
      imipenem and the aminoglycosides still retained excellent activity against most
      multiresistant species. Although there were wide differences between hospitals in
      the frequencies of resistance to most antibiotics, these were not related to the
      types (general vs. university) of hospitals or to the number of beds. Some
      variations were however observed in the distribution of bacterial species: the
      prevalence of inducible Enterobacteriaceae was significantly higher in university
      than in general hospitals and in hospitals located in Brussels and in Wallonia
      than in the Flanders. Overall few trends in resistance rates were observed in
      comparison to a similar survey performed in 1991.

PMID- 9562704
TI  - Chronic lymphocytic alveolitis with migrating pulmonary infiltrates after
      localized chest wall irradiation.
AB  - In a number of patients, radiotherapy following surgery for breast carcinoma may
      induce radiation injury to the lungs. This has classically been divided into an
      early radiation pneumonitis and a late fibrosis, both confined to the irradiated
      lung volume. However we observed a female patient who similarly to other recent
      reports in the literature developed a recurring pneumonitis migrating from one
      lung to the other after radiotherapy for breast carcinoma. This migratory BOOP
      (bronchiolitis obliterans organizing pneumonia) was characterized by a
      lymphocytic alveolitis and responded well to corticosteroids. Clinicians should
      be aware of the possibility of a lymphocytic pneumonitis in both lungs after
      unilateral thoracic irradiation and recognize the distinctive features of fever,
      cough, dyspnoea and malaise in order to start an effective treatment with
      corticosteroids. They should also be aware of the high tendency for recurrence
      when tapering off.

PMID- 9562705
TI  - Tracheal laceration and tension pneumomediastinum of spontaneous favorable
      outcome.
AB  - The case of a 75-year-old women with probable tracheal laceration and tension
      pneumomediastinum after intubation is reported. A dramatic reduction of tracheal
      caliber was observed during fiberoptic bronchoscopy. Despite severe dyspnea, the
      patient healed with conservative measures. We conclude that aggressive surgical
      treatment for tracheal laceration is not always necessary.

PMID- 9562706
TI  - Obstructive hydrocephalus as complication of a giant nonfunctioning pituitary
      adenoma: therapeutical approach.
AB  - We report the case of a 61-year-old male presenting with a giant nonfunctioning
      pituitary tumour extending into the third ventricle and thereby causing
      obstructive hydrocephalus. The main complaints consisted of disturbed vision and
      somnolence. The patient was initially treated by ventriculoperitoneal shunting,
      with immediate improvement of his mental status. Transcranial resection of the
      tumour was performed shortly thereafter, but only a limited part of the tumour
      could safely be removed. By immunohistochemistry the diagnosis of gonadotroph
      adenoma was made. After the operation, the patient's vision deteriorated
      temporarily. Because of the risk of further damage to the optic nerve, radiation
      therapy was postponed. Instead, treatment with the long-acting dopamine agonist
      cabergoline was instituted, which resulted in a gradual improvement of vision.
      Two years later a transsphenoidal operation was performed because of acute
      worsening of the visual fields due to central tumour necrosis with slight volume
      expansion. Vision improved considerably after surgery. Radiotherapy is scheduled
      in the near future. This case is an illustration of the complications of giant
      nonfunctioning pituitary adenomas. The therapeutical approach to obstructive
      hydrocephalus in these instances is reviewed.

PMID- 9562707
TI  - Chronic dissection of the thoracic aorta in a patient with tuberculous pleuro
      pericarditis.
AB  - We describe a case of chronic dissection of thoracic aorta presumed to be due to
      tuberculosis from pleuro-pericarditis foci and who was cured by antituberculous
      therapy and surgery. With the recent increase of tuberculosis cases, tuberculous
      aortitis might become less rare and the clinicians should suspect this diagnosis
      in subjects with aortic dissection and history of tuberculosis.

PMID- 9562708
TI  - Prevalence of Escherichia coli O157:H7.

PMID- 9562709
TI  - Extensive outbreak of food-borne illness in Hasselt: was it Escherichia coli
      O157:H7?

PMID- 9562710
TI  - [Adhering to the standards of diabetes management].

PMID- 9562711
TI  - [Malaria drug for African poor in sight].

PMID- 9562713
TI  - [Laser therapy of pigment spots and tattooing. Selecting indications carefully-
      choice of suitable laser equipment].

PMID- 9562712
TI  - [Laser applications in dermatology].
AB  - Over the past decades continuous wave laser systems have been used in dermatology
      for the photocoagulation and vaporization of vascular neoformations and
      malformations and to remove epithelial lesions. However, their mainly thermal
      effect can have negative impact on wound healing and scar formation due to
      thermal damage of adjacent tissue. More recent laser systems now permit more
      selective and more restrictive destruction of pathological tissue. They include
      pulsed and Q-switched lasers matched to the absorption characteristics of the
      target structures, which permit skin ablation and selective photothermolosysis of
      pigmented or vascular lesions. These technical innovations have expanded the
      therapeutic spectrum in dermatology and improved the quality of the results
      achieved. Nevertheless, these systems should be used only for carefully selected
      indications, in particular when corrective-aesthetic considerations are of
      importance. Furthermore, prior to treatment, it is mandatory for the
      dermatologist, to establish the proper diagnosis, especially in the case of
      pigmented lesions and skin changes of uncertain dignity.

PMID- 9562714
TI  - [Carefully assessing the risk of melanoma. Screening by questionnaire alone is
      too risky].

PMID- 9562715
TI  - [Alzheimer patients frequently minimize their illness. Interview with Priv.-Doz.
      Dr. med. Ulrich Hegerl, Munich, about rational Alzheimer diagnosis. Interview by
      Dr. med. vet. Yvette Zwick].

PMID- 9562716
TI  - [Common root for degenerative encephalopathies? Pathophysiologic background for
      Huntington chorea--amyloid as in Alzheimer disease, Parkinson disease or
      Creutzfeldt-Jakob disease are detected].

PMID- 9562717
TI  - [Interstitial lung diseases and oxidant burden. Pathogenetic connection between
      alveolitis and fibroblast stimulation].

PMID- 9562718
TI  - [Acne inversa].

PMID- 9562719
TI  - [Frequent air travel. Visit to the medical service of Lufthansa].

PMID- 9562720
TI  - [Chlamydia infections].

PMID- 9562721
TI  - [Bronchial asthma from Chlamydia pneumoniae? Epidemiology, risk factors and
      practical consequence for therapy].

PMID- 9562722
TI  - [Drug administration to the mouth mucosa. Modern oral adhesive drug forms].

PMID- 9562723
TI  - [Thermal stability of grain allergens].

PMID- 9562724
TI  - [A classic example of infectious endocarditis?].
AB  - A 15-year-old girl in whom the diagnosis of infective endocarditis was
      established was sent to our cardiothoracic centre for mitral valve replacement
      because of a streptococcal endocarditis resistant to adequate antibiotic therapy.
      Despite the combination of fever, a 'new' heart murmur, 'positive blood cultures'
      and 'vegetations' on the mitral valve, the clinical picture gave rise to some
      doubt about the diagnosis. Finally the diagnosis of systemic lupus erythematosus
      was made and after treatment with corticosteroids all symptoms disappeared. In
      our modern era 'simple symptoms' still play a very important part in clinical
      decision making.

PMID- 9562726
TI  - [Safety of blood transfusions; need for 'hemo-vigilance'].
AB  - Blood transfusion in the Netherlands depends wholly on voluntary donations of
      blood. Very soon the measures to ensure the safety, the quality and clinical
      appropriateness of the application of blood products will be re-evaluated.
      Currently it is not so much viral but bacterial contamination that causes worry,
      in addition to immunological transfusion reactions. Safety not only depends on
      freedom from viral or bacterial contamination, but also on the appropriate
      clinical use of blood products. Physicians will need to document the individual
      indications for the use of blood products and the patient's reactions at follow
      up. European legal harmonisation emphasises look-back procedures and
      haemovigilance as a means of ensuring sound clinical practice regarding blood
      transfusion.

PMID- 9562725
TI  - [Secondary prevention following cerebral ischemia: is monotherapy with
      acetylsalicylic acid still first choice?].
AB  - Acetylsalicylic acid (ASA) alone (at least 30 mg per day) in post-cerebral
      ischaemia patients reduces the relative risk of further vascular events by 13%
      compared with placebo. A meta-analysis of all studies shows that the combination
      of ASA with dipyridamole reduces the relative risk by 16% (95% confidence
      interval: 5-26%) compared with ASA alone, but confirmation by a major trial
      appears desirable, because of discrepant results of a recent trial and 4 previous
      ones. Clopidogrel might reduce the risk by 7% compared with ASA alone, but this
      drug is expected to be expensive. Anticoagulation therapy with an international
      normalized ratio (INR) of 2.0-4.0 is particularly efficacious for secondary
      prevention in patients with atrial fibrillation, but anticoagulation therapy with
      an INR of 3.0-4.5 is not safe in secondary prevention of cerebral ischaemia of
      presumed arterial origin. Finally, not all atherosclerotic vascular diseases are
      identical from the therapeutic point of view; the effect of treatment depends in
      part on the clinical manifestation form.

PMID- 9562727
TI  - [Optimal versus maximal safety of the blood transfusion chain in The Netherlands;
      results of a conference. College for Blood Transfusion of the Dutch Red Cross].
AB  - An invitational conference was held on September 11, 1996 by the Medical Advisory
      Commission to the Blood Transfusion Council of the Netherlands Red Cross,
      addressing the issues of 'maximal' versus 'optimal' safety measures for the blood
      supply. Invited were blood transfusion specialists, clinicians, representatives
      of patient interest groups, the Ministry and Inspectorate of Health and members
      of parliament. Transfusion experts and clinicians were found to advocate an
      optimal course, following strategies of evidence-based medicine, cost-benefit
      analyses and medical technology assessment. Patient groups depending on blood
      products, such as haemophilia patients would rather opt for maximal safety.
      Insurance companies would choose likewise, to exclude any risk if possible.
      Health care juridical advisers would advise to choose for optimal safety, but to
      reserve funds covering the differences with 'maximal safety' in case of
      litigation. Politicians and the general public would sooner choose for maximal
      rather than optimal security. The overall impression persists that however small
      the statistical risk may be, in the eyes of many it is unacceptable. This view is
      very stubborn.

PMID- 9562728
TI  - [Antiepileptics].
AB  - Despite introduction of new antiepileptic drugs the established drugs phenytoin,
      carbamazepine and valproate still provide the treatment of choice in most forms
      of epilepsy, being efficacious in approximately two-thirds of all newly referred
      patients. In 20-60% of patients resistant to treatment with the older drugs, a
      50% reduction of seizure frequency can be achieved by adding ethosuximide,
      clobazam, vigabatrine, oxcarbazepine, lamotrigine, felbamate, tiagabine or
      topiramate to the classic treatment. The majority of the new drugs are free of
      the problematic enzyme induction of the older compounds, making monotherapy as
      well as combination therapy much easier. To what extent the new antiepileptic
      drugs are going to be used for the treatment of patients with epilepsy will
      depend on the analysis of cost and benefits. This will be based on efficacy, side
      effects, interactions and teratogenicity of these new compounds.

PMID- 9562729
TI  - [Survey on blood transfusion policy within Dutch hospitals: wide discrepancies.
      Central Guidance Organization for Peer Review].
AB  - OBJECTIVE: To describe the transfusion practices in Dutch hospitals. DESIGN:
      Descriptive. METHOD: Late in 1995 a questionnaire was sent to the heads of the
      transfusion laboratories of all Dutch hospitals. RESULTS: The response was 91%
      (117/128). A large variation was found not only in the ways transfusion medicine
      was organised but also in laboratory methods used. CONCLUSION: The implementation
      of the consensus agreements on blood transfusion in the Netherlands (1983,
      revised in 1989) is poor. Continuous education of the participants should be
      encouraged. Implementation of these agreements could be facilitated by active
      participation of the blood bank in the transfusion committees of each hospital.

PMID- 9562732
TI  - [Psychogenic erection and ejaculation disorders in a couple wanting children].
AB  - A man aged 40 and his wife aged 29, involuntarily childless due to a psychogenic
      disturbance of erection and ejaculation, asked for donor insemination. The man
      had been given psychosexual treatment without success during the preceding 4
      years. Before starting donor insemination an ultimate effort to obtain an
      ejaculate by means of electrovibrator treatment was made, the physician handling
      the instrument. Two pregnancies were achieved by insemination with semen of the
      husband. The question is raised whether in a couple with a psychogenic coital
      disorder who only wish to achieve pregnancy, psychosexual therapy is indicated.

PMID- 9562730
TI  - [2nd revision consensus on blood transfusion. Central Guidance Organization for
      Peer Review].
AB  - Since 1982 several consensus conferences regarding the transfusion practice in
      hospitals have been organized in the Netherlands. Repeated updating of the
      consensus text such as described in this article is required to keep abreast of
      new developments and changes in clinical practice. Guidelines concerning
      compatibility testing (the result of compatibility testing is valid for three
      days at most), the organization of responsibilities and the clinical use of red
      cell concentrates, including a protocol for transfusion in patients with massive
      bleeding, were changed. No consensus was reached concerning the need to use only
      red cells that are antigen c, E and K compatible in women younger than 45 years
      of age and in patients with abnormal erythropoiesis. Although the need of
      systematic reviews to support guidelines was recognized, literature reviews
      revealed that only few studies were designed well enough to allow definitive
      conclusions regarding the benefits and risks of red cell transfusion.

PMID- 9562733
TI  - [Prevention of vascular complications following cerebral ischemia of arterial
      origin; the ESPRIT trial: mild anticoagulant therapy, combination treatment with
      acetylsalicylic acid plus dipyridamole or treatment with acetylsalicylic acid
      alone?].
AB  - The European and Australian Stroke Prevention in Reversible Ischaemia Trial
      (ESPRIT) is a randomised clinical trial in which patients with cerebral ischaemia
      of arterial origin will be randomised between oral anticoagulation (international
      normalized ratio (INR): 2.0-3.0), the combination of acetylsalicylic acid (in any
      dose between 30 and 325 mg per day) plus dipyridamole (400 mg daily) and
      acetylsalicylic acid only (in any dose between 30 and 325 mg per day). It is
      planned to enroll 4500 patients with a mean follow-up of three years. Primary
      outcome is the composite event of vascular death, stroke, myocardial infarction,
      or major bleeding complication; outcome assessment will be blinded. ESPRIT is an
      international, multicentre study in which 60-80 hospitals in the Netherlands and
      other countries in Europe and Australia will participate.

PMID- 9562734
TI  - [Immunology in medical practice. VII. Psoriasis].

PMID- 9562735
TI  - [Medical education of tomorrow: a glance into the (near) future].

PMID- 9562736
TI  - [Skating fun and fractures of the maxillofacial bones].
AB  - Skating is a favourite sport in the Netherlands. Injury data on skating were
      collected from the emergency departments of 6 hospitals in the province of
      Friesland in the Netherlands during the Eleven Cities ice skating marathon over
      200 kilometers in January 1997, with 16,688 participants. Among a total of 55
      fractures, the maxillofacial skeleton had a relative high fracture frequency (n =
      7; 13%), especially the zygomatic complex (n = 6); one patient had a mandibular
      fracture. An innocent-looking black eye, unilateral numbness of the upper lip and
      malocclusion following a skating accident merit full medical attention.

PMID- 9562737
TI  - [Medical consequences of the 15th Eleven-Cities skating marathon].
AB  - The 15th Dutch Eleven Cities ice skating marathon was run on Saturday 4th January
      1997. Numerous measures were taken to reduce the risk of accidents: active or
      standby were 7 hospitals, 3 helicopters for transport of casualties, 60 first-aid
      stations along the route, 600 first-aiders, 120 Red Cross workers, 50 GPs, 10
      diving teams and a large police presence. A total of 150 ambulance rides were
      made and 151 skaters with 179 injuries were treated in the hospitals. The number
      of treatments administered in the first-aid stations was 2393 (14.3% of the total
      number of participants), including 829 cases of frostbite/hypothermia. Of the
      16,387 participants of 1997, 11,523 (70.3%) finished.

PMID- 9562738
TI  - [Immunology in clinical practice. X. IgG receptors: structure, function and
      immunotherapy].
AB  - Receptors for the constant or Fc part of IgG (Fc gamma R) constitute an important
      link between the humoral and cellular parts of our immune system. Fc gamma R
      expressed on leukocytes are capable of initiating immunological effector
      functions such as phagocytosis, antibody dependent cellular cytotoxicity (ADCC),
      degranulation, release of inflammatory mediators, production of oxygen radicals
      and regulation of antibody production. Soluble Fc gamma R in plasma play a
      modulator role in the immune system. The Fc gamma R expressed on endothelial
      cells (Brambell receptor: FcRB) is involved in regulation of IgG levels in blood
      and transport of maternal IgG to the unborn child. Experimental immunotherapy
      directed against haematological and solid tumours exploiting Fc gamma R-mediated
      functions has shown promising results.

PMID- 9562739
TI  - [Immunology in clinical practice. XI. IgG receptors: the role of polymorphism in
      autoimmune and infectious diseases].
AB  - Receptors for the constant part of IgG (Fc gamma R) are implicated in the
      pathogenesis of a number of diseases. Children from mothers with an Fc gamma
      RIIIb deficiency may suffer from neonatal neutropenia due to an alloimmune
      reaction. Interindividual differences (polymorphisms) for a number of Fc gamma R
      represent risk factors for several infectious and autoimmune diseases.
      Immunotherapeutic use of several monoclonal antibody subclasses is affected by Fc
      gamma R polymorphisms. Fc gamma R can be used for cellular entrance by
      lymphotropic viruses (such as HIV) and appear to be involved in the pathogenesis
      of fulminant Dengue virus infections.

PMID- 9562740
TI  - [Eleven-Cities skating marathon and the windchill factor].
AB  - The weather conditions during the 15th Eleven Cities ice skating marathon (200
      kilometers) in Friesland (the Netherlands) on 4 January, 1997, were better than
      predicted. For measurement of the windchill factor the Steadman scale is
      preferred to the Siple and Passel scale. For ice skaters the windchill factor is
      lower than for the spectators, due to the drag effect.

PMID- 9562741
TI  - [Causes of spread and return of scabies in health care institutes; literature
      analysis of 44 epidemics].
AB  - OBJECTIVE: To determine the risk factors that contribute to the transmission and
      return of scabies in health care institutions. DESIGN: Literature analysis.
      SETTING: Public Health Care Service Midden-Kennemerland. Heemskerk, the
      Netherlands. METHODS: Search of Medline over the years 1976-1996 yielded 34
      reports of 44 outbreaks. The contents were qualitatively examined on factors
      possibly contributing to the transmission and return of scabies in health care
      institutions. RESULTS: Six such factors that contribute to the transmission and
      return of scabies in health care institutions were found: (a) among residents in
      health care institutions a considerable number are, once infested, at risk of
      developing crusted scabies, (b) many people are exposed through close contact,
      (c) the generally long diagnostic delay, (d) insufficient survey of the
      epidemiological problem, (e) treatment failures and (f) incomplete post
      intervention monitoring.

PMID- 9562742
TI  - [Measurement of colon transit time useful in the evaluation of functional
      constipation].
AB  - OBJECTIVE: To determine the colon transit time (CTT) in patients complaining of
      functional constipation and the correlation between abnormal transit times and
      the types of constipation and of the symptoms. DESIGN: Retrospective,
      descriptive. SETTING: Department of Surgery, University Hospital, Nijmegen, the
      Netherlands. METHOD: The signs and symptoms of 112 patients with infrequent or
      difficult defaecation, 93 (83%) of them women, with a median age of 42 years
      (range: 16-72), were recorded by means of a questionnaire. After ingestion of
      radiopaque markers per day for 10 days, an abdominal survey X-ray was made on day
      11. The numbers of markers in the X-ray and per segment (right and left hemicolon
      and rectosigmoid) were counted; the CTT in hours was calculated by multiplying
      this number by 2.4. Slowness was defined as more than 45 h for the total CTT and
      as more than 15 h for the segmental CTT. RESULTS: The total CTT was normal in 33
      patients (29%) and prolonged in 79 (71%). The CTT was prolonged only in the
      rectosigmoid in 14 patients with a normal CTT (42%) and in 50 patients with a
      prolonged total CTT (63%). Of the patients with a normal total CTT, 13 (39%) had
      a normal segmental CTT. No statistically significant correlation could be
      demonstrated between the presence of any symptom and a prolonged CTT. CONCLUSION:
      Functional constipation may be associated with a normal CTT. Disorders of colonic
      motility and of rectal evacuation could be distinguished by measuring the total
      and the segmental colonic transit times.

PMID- 9562743
TI  - [Neutropenia due to antibodies against Type III Fc receptors on neutrophil
      granulocytes: 3 children with different clinical courses].
AB  - Three children (girls) suffered from neutropenia mediated by anti-neutrophil IgG
      Fc receptor type III (Fc gamma RIII) antibodies. The first patient (newborn) had
      asymptomatic and transient neutropenia caused by maternal Fc gamma RIII iso
      antibodies. The second patient (6 months), whose neutropenia was diagnosed as a
      'benign neutropenia of childhood' caused by transient anti-NAI autoantibodies,
      suffered from mild bacterial infections. The third patient (12 years) suffered
      from serious infections. The anti-Fc gamma RIII autoantibodies showed neither
      anti-NA1 nor anti-NA2 specificity. She also developed autoimmune thyroiditis
      (Graves' disease). Both the duration of the neutropenia and the seriousness of
      the bacterial infection were variable in our patient group. The first two
      patients both made spontaneous recoveries, while the third patient depended
      ultimately on granulocyte-colony stimulating factor (G-CSF).

PMID- 9562744
TI  - [Plastic surgery treatment of a nose tip amputation in an Eleven-Cities marathon
      skater].
AB  - A 41-year-old male participant of the 200 km Eleven Cities ice skating marathon
      in 1997 lost a large part of his nose tip as a result of hitting a bridge.
      Avascular replantation of the amputated nose tip combined with ice water cooling
      for three days did not result in revascularisation. Subsequently the entire nose
      tip was reconstructed by means of a paramedian forehead flap. This reconstruction
      was performed in three stages and had a good aesthetic result.

PMID- 9562745
TI  - [Penicillin: just in time].

PMID- 9562746
TI  - [Penicillin: just in time].

PMID- 9562747
TI  - [Penicillin: just in time].

PMID- 9562748
TI  - [Penicillin: just in time].

PMID- 9562750
TI  - [Risk factors for a complicated illness course in children hospitalized with
      measles in a Philippine university hospital].

PMID- 9562751
TI  - [A patient with generalized actinomycosis].

PMID- 9562752
TI  - [Medical education: 'plus ca change, plus c'est la meme chose'].

PMID- 9562754
TI  - [The treatment of idiopathic facial paralysis].
AB  - Current drug treatment of Bell's palsy often consists of prednisone for patients
      with a complete paralysis. Since it was demonstrated that herpes simplex plays a
      role in the pathogenesis of Bell's palsy, antiviral therapy may become the
      treatment of choice. Six randomized controlled trials comparing prednisone with
      placebo have been performed: four of them did not conform to the criteria for
      good clinical trials. The remaining two trials did not demonstrate therapeutic
      efficacy of prednisone. A recently published randomized controlled trial
      comparing prednisone and acyclovir with prednisone and placebo showed a
      statistically significant and clinically important superiority of the combination
      therapy. This trial, however, also had methodological flaws and its results
      should be interpreted with caution. In our opinion, further evidence is needed
      before acyclovir should be given routinely to patients with Bell's palsy.

PMID- 9562755
TI  - [Cause of Bell's palsy: herpes simplex virus].
AB  - At present Bell's palsy (BP) is still defined as idiopathic unilateral facial
      paralysis of sudden onset. More than 20 years ago an aetiological link between
      herpes simplex virus (HSV) and BP was proposed. Numerous experiments in animals
      and in humans have been performed to test this hypothesis. However, the human
      facial nerve tissue itself was investigated in only a few of these studies. Two
      research lines were followed: (a) search for presence of latent HSV in the facial
      nerve of asymptomatic individuals (as shown earlier in the trigeminal nerve); (b)
      find 'active' HSV in tissues from BP patients with recent onset of disease. The
      application of new molecular biological techniques, notably polymerase chain
      reaction (PCR), to facial nerve tissues has provided ample evidence for a causal
      relationship between BP and HSV. Therefore it might now be the time to change the
      name 'Bell's palsy' into 'herpetic facial paralysis'.

PMID- 9562756
TI  - [Immunology in clinical practice. XIII. Immune diseases of the eye].
AB  - The eye has a special relationship with the immune system; normally, there
      appears to be intraocular suppression of inflammatory responses. Studies of the
      immunological principles of intraocular inflammation (uveitis) are mostly done in
      animal models. Although very complicated, uveitis appears in any case to be T
      cell mediated. Uveitis is classified according to anatomical location as
      anterior, intermediate, posterior and pan-uveitis. Other immunological disorders
      are the sicca syndrome, keratitis and scleritis. All these disorders may or may
      not be associated with systemic autoimmune diseases. The chronic and recurring
      characteristics make uveitis a serious threat to vision. A rapid diagnosis and
      adequate treatment are therefore very important.

PMID- 9562753
TI  - [Treatment of restlessness in dying patients: more than just sedation].
AB  - Restlessness can make dying unnecessarily difficult, not only for the patient
      himself, but also for his family and the physician in charge. Four cancer
      patients, three men aged 69, 80 and 66 and a woman aged 88, displayed severe
      terminal restlessness, caused by nicotine abstinence, hypoglycaemia, constipation
      and urinary retention, respectively. Suitable interventions helped the patients
      to die in peace and dignity. Facing restless terminal patients the physician
      should think of withdrawal symptoms, metabolic derangements, full bladder and
      (or) rectum and intoxication by drugs, frequently morphine. Interventions
      directed at those problems may bring surprising results.

PMID- 9562757
TI  - [Viral hemorrhagic fever].
AB  - Viral haemorrhagic fevers, such as Lassa fever and yellow fever, cause tens of
      thousands of deaths annually outside the Netherlands. The viruses are mostly
      transmitted by mosquitoes, ticks or via excreta of rodents. Important to
      travellers are yellow fever, dengue and Lassa and Ebola fever. For yellow fever
      there is an efficacious vaccine. Dengue is frequently observed in travellers;
      prevention consists in avoiding mosquito bites, the treatment is symptomatic.
      Lassa and Ebola fever are extremely rare among travellers; a management protocol
      can be obtained from the Netherlands Ministry of Health, Welfare and Sports.
      Diagnostics of a patient from the tropics with fever and haemorrhagic diathesis
      should be aimed at treatable disorders such as malaria, typhoid fever,
      rickettsiosis or bacterial sepsis, because the probability of such a disease is
      much higher than that of Lassa or Ebola fever.

PMID- 9562758
TI  - [Efficacy of antibiotics in frequently occurring airway infections in family
      practice].
AB  - Dutch prescription percentages of antibiotics for respiratory tract infections in
      general practice are relatively low compared with international figures. Moreover
      the spectrum of different kinds of antibiotics is rather limited compared with
      for instance the USA. The results of recent RCTs and the guidelines of the Dutch
      College of General Practitioners are a firm scientific basis for a restrictive
      prescription behaviour. Antibiotics are in general only indicated in risk groups
      (young children and the elderly). Patients accept withholding of antibiotics
      better than doctors expect. Comparison of data of a nationwide study in general
      practice in a period just before the publication of these guidelines with
      estimated evidence-based prescription percentages shows that the actual behaviour
      was not in line with the state of the art. This is especially true of acute
      bronchitis and rhinosinusitis and to a lesser extent of sore throat.

PMID- 9562759
TI  - [Topical corticosteroid injection for 'trigger finger': good short-term results,
      but fairly high risk of recurrence].
AB  - OBJECTIVE: To determine the short and long term results of trigger fingers
      treated with a local injection of corticosteroid. DESIGN: Prospective analysis.
      SETTING: 'Zuiderziekenhuis', Department of General Surgery, Rotterdam, the
      Netherlands. METHOD: In 55 patients with 62 trigger fingers the affected flexor
      sheath was injected with a long-acting corticosteroid. All patients were followed
      up for at least one year. RESULTS: With one or two steroid injections 60 of the
      62 trigger fingers were treated successfully. During the follow-up period the
      cumulative recurrence rate was 33% after one year. CONCLUSION: The treatment of
      trigger fingers with a local injection of steroids is a simple and safe procedure
      but the risk of recurrence in the first year is considerable.

PMID- 9562760
TI  - [High incidence of admissions for schizophrenia in Surinam patients in The
      Netherlands not caused by preferential immigration of (pre)schizophrenic
      patients].
AB  - OBJECTIVE: To answer the question whether positive selection of
      (pre)schizophrenic Surinams in Surinam before emigration to the Netherlands can
      explain the high admission rates for schizophrenia of Surinams in the
      Netherlands. DESIGN: Retrospective research. SETTING: 's Lands Psychiatrisch
      Ziekenhuis (National Psychiatric Hospital) Paramaribo, Surinam (LPZ). METHOD: The
      Netherlands Central Bureau of Statistics in Voorburg and the Central Registry
      Office in Paramaribo provided data on emigration to the Netherlands of the
      Surinam population and on remigration. Files of (pre)schizophrenic patients were
      selected from the records of LPZ. Subsequently, these patients were traced and
      their pattern of migration was studied. Using the chi 2 test the significance of
      observed differences was assessed. RESULTS: Surinam (pre)schizophrenic patients
      did not emigrate more frequently to the Netherlands (6.3%) compared with the
      Surinam population in general (9.6%) and they remigrated more frequently to
      Surinam than the Surinams in general. CONCLUSION: The positive selection
      hypothesis must be rejected.

PMID- 9562761
TI  - [Coronary stenosis following successful radiotherapy for Hodgkin disease].
AB  - Three male patients, aged 43, 41 and 44 years, were referred to the cardiologist
      because of complaints of angina pectoris; one of them also had an aortic valve
      stenosis. Nine to 22 years before, they had received radiotherapy on the
      mediastinum because of Hodgkin's disease. Coronary angiography showed severe
      stenoses of the ostium of the right coronary artery or of the main left coronary
      artery, following which the patients were treated with coronary artery bypass
      surgery, aortic valve replacement and (or) drugs. These locations are very
      unusual in patients with angina who did not receive any radiation therapy, but
      they are seen frequently in patients who have received radiotherapy on the
      mediastinum. The pathogenesis of these lesions is not exactly known. The normal
      risk factors for atherosclerosis plus free oxygen radicals are probably involved.
      The free oxygen radicals, generated by radiation, locally activate coagulation
      via various hypothetical mechanisms. The damaging effect of radiotherapy could
      therefore be prevented by antioxidants. However, the therapeutic effect of
      radiation would most likely decrease as well. A more rational approach to prevent
      these vascular lesions would be to reduce the radiation load, to treat the risk
      factors for atherosclerosis and to give platelet aggregation inhibitors such as
      acetylsalicylic acid.

PMID- 9562762
TI  - [History of healing; wound suturing].
AB  - The history of wound suturing reflects that of surgery itself. In wound
      treatment, which encloses the technique of suturing as well as suturing
      materials, wound suturing plays a prominent role. In ancient India, Egypt and the
      Greek and Roman societies wound treatments as well as suturing techniques and
      instruments were developed that strongly resemble those in our days. Catgut and
      silk are known since antiquity. Hardly any progress is noted up to the nineteenth
      century. The debate on closed or open wound treatment has never stopped. The
      improvement of catgut by Lister started in 1860. In the 19th century prototypes
      of mechanical suturing instruments (staplers) were developed. They were
      introduced into clinical practice in the early decades of the 20th century. The
      greatest progress in wound suturing started after World War II with the
      introduction of advanced semiautomatic stapler machinery and with the manufacture
      of synthetic non-resorbable and resorbable fibres. They have revolutionized
      surgery and were instrumental in developing new fields (microsurgery).

PMID- 9562763
TI  - [Acute dystonia].

PMID- 9562764
TI  - [Need for centralization of pediatric intensive care].

PMID- 9562765
TI  - [Finishing a pregnancy in an infaust fetal prognosis].

PMID- 9562766
TI  - [Finishing a pregnancy in an infaust fetal prognosis].

PMID- 9562767
TI  - [Finishing a pregnancy in an infaust fetal prognosis].

PMID- 9562768
TI  - [Multi-disciplinary treatment of cerebral arteriovenous malformation: preliminary
      results in 115 consecutive patients].

PMID- 9562769
TI  - [A cholesterol-lowering diet is not useful].

PMID- 9562770
TI  - [Acute pancreatitis in children].
AB  - Acute pancreatitis is probably commoner in children than was previously thought.
      In children it is most commonly associated with trauma or viral infection. The
      presentation may be subtler than in adults, requiring a high index of suspicion
      in the clinician. In three children, two boys aged 4 and 10 and a girl of 15
      years, acute pancreatitis was suspected because of the findings at
      ultrasonography and endoscopic retrograde cholangiopancreatography performed when
      the disease recurred (the boy aged 4), apathy and immobility without dehydration
      or other obvious causes (the boy aged 10), and severe abdominal pain in
      combination with vomiting (the girl). All three patients had severely increased
      (urinary) amylase levels. Most often, acute pancreatitis in children tends to be
      a self-limiting disease which responds well to conservative treatment.

PMID- 9562771
TI  - [Variations in health: a starting point for quality assurance in health care].
AB  - Variations in health outcomes may reflect variations in the quality of care. The
      monitoring of health outcome variations (for example between hospitals or groups
      of caregivers) may therefore be considered as an instrument for quality
      assessment in health care. As health care is not the only determinant of health,
      further research is needed to find out whether health outcome variations are
      related to variations in the quality of care. Until now, health outcomes have
      been based mainly on mortality and morbidity measures. In the Netherlands various
      registries are useful for the monitoring of health outcome variations, such as
      the cause of death statistics, the national medical registry, the national
      obstetrics registry and the complications registry of the Netherlands Association
      of Surgeons.

PMID- 9562772
TI  - [Immunology in clinical practice. XII. Indications for T-Cell-mediated
      immunotherapy of cancer].
AB  - In a limited number of cases, T cell based cancer immunotherapy has proven its
      clinical efficacy. Indications are restricted to certain haematological
      malignancies, relapsed after allogeneic bone marrow transplantation, and tumours
      against which an autologous T cell response can be elicited or boosted, such as
      melanomas and renal carcinomas. T cell based immunotherapy of non-immunogenic
      tumors is possible using bispecific antibodies.

PMID- 9562773
TI  - [Short-acting insulin analogs].
AB  - Patients with diabetes mellitus type I usually are treated with a multiple
      injection regimen comprising rapid-acting insulin before meals and intermediate
      acting insulin at bedtime. Recently, the rapid-acting insulin analogue insulin
      LISPRO was introduced on the Dutch market. This form of insulin is very rapidly
      taken up into the bloodstream from the subcutaneous tissue. The advantages of the
      use of insulin LISPRO are the comfort of injecting the insulin just before a
      meal, the more rapid correction of incidental hyperglycaemia and the slightly
      lower incidence of (nocturnal) hypoglycaemia in comparison with conventional
      rapid-acting insulin. There is no argument in favour of switching diabetics to
      insulin LISPRO if they are well-controlled with normal rapid-acting insulin and
      have few episodes of hypoglycaemia. In some persons the duration of action of
      insulin LISPRO may be too short, leading to preprandial hyperglycaemia. This can
      be avoided by using a second injection of intermediate-acting insulin, either
      before breakfast or before lunch.

PMID- 9562774
TI  - [Medical-scientific research in the elderly in The Netherlands; historic
      milestones and methodological problems].
AB  - OBJECTIVE: To describe the methodological development of medical research
      regarding elderly subjects in the Netherlands. DESIGN: Descriptive. SETTING:
      Nijmegen University, the Netherlands. METHOD: All research on aging published in
      the Netherlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) starting
      from its first volume in 1857 up to 1983 was studied. Selected were those
      articles in which new research methods were introduced. Next, six pioneering
      researchers in geriatrics were interviewed on the methodological development of
      geriatric research and on the problems they encountered in their own research.
      RESULTS: Research started with studies on age-associated diseases such as
      prostatism, presbyacusis and senile dementia. It was only after a considerable
      delay that new diagnostic instruments such as electrocardiography and new
      research designs such as randomized trials found their way into research on
      elderly patients. The development of a questionnaire on the health of the
      elderly, the introduction of the concept of activities of daily living and of
      diagnostic instruments in the field of psychogeriatrics were important steps that
      made possible current geriatric research. From the outset, researchers
      encountered methodological problems still relevant in current research and caused
      by characteristics of geriatric patients: frailty, high prevalence of
      comorbidity, coexistence of physical, psychological and social problems, and
      large interindividual differences.

PMID- 9562775
TI  - [Risk factors for the development of phlebitis in peripheral infusions].
AB  - OBJECTIVE: To study the incidence and risk factors of development of phlebitis
      caused by peripheral infusions. DESIGN: Prospective, descriptive. SETTING:
      Westindies Hospital, The Hague, the Netherlands. METHODS: For all 348 patients
      given infusions in a 6-week period the development of phlebitis, if any, and the
      contributing factors were studied. RESULTS: Phlebitis developed in 136 patients
      (39%), after an average of 2.9 days (range: 1-14). Risk factors were female sex,
      earlier phlebitis, insertion on the ventral surface of the forearm and
      administration of antibiotics via the infusion. These factors were not
      interdependent. No correlation was found between development of phlebitis and the
      size of the needle. CONCLUSION: Development of phlebitis depends on a number of
      factors. Timely removal of the infusion can prevent the development of phlebitis.
      Infusions should preferably be administered via the hand.

PMID- 9562776
TI  - [Maternal serum screening for Down syndrome and neural tube defects].
AB  - OBJECTIVE: Evaluation of maternal serum screening for Down's syndrome (DS) and
      neural tube defects (NTDs). DESIGN: Longitudinal study. SETTING: Department of
      Obstetrics and Gynaecology, University Hospital Utrecht, the Netherlands. METHOD:
      6362 pregnant women underwent serum screening for DS and (or) NTD between the
      15th and 21st weeks of pregnancy between March 1991 and March 1996. Screening was
      performed using alpha-foetoprotein, unconjugated oestriol, human chorionic
      gonadotrophin and maternal age. The result of each individual test was a
      calculated risk for delivering a child with DS and (or) NTD. RESULTS: Nine out of
      12 singleton pregnancies of a foetus with DS were detected. To this purpose, 573
      women who, according to the serum screening had an increased risk of a child with
      the abnormality, were offered amniocentesis, which was performed in 471 of them.
      Two twin pregnancies with a total of 3 DS affected foetuses were also detected;
      one twin pregnancy of a DS foetus was screen-negative. The one case of spina
      bifida was screen-positive. The proportion of women eligible for invasive
      prenatal diagnosis because of maternal age increased from 9% to 25% in the course
      of the study. Of 1118 women aged > or = 36 years 913 (82%) declined invasive
      investigation compared with 40% in the general population. CONCLUSION: The
      results of the maternal serum screening program in Utrecht were comparable with
      other studies. Maternal serum screening is accepted as an alternative by women
      above 36 years, and allows to decrease the need for amniocentesis without a
      significant loss in detection rate.

PMID- 9562778
TI  - [Biochromophore indicators in the German formulary].

PMID- 9562777
TI  - [Hepatic steatosis during treatment with zidovudine and lamivudine in an HIV
      positive patient].
AB  - A 33-year-old HIV-infected man was given antiretroviral therapy with zidovudine
      and lamivudine. After ten months' treatment the patient had elevated hepatic
      transaminase levels. Severe hepatic steatosis was found in the biopsy. Clinical
      history, laboratory, microbiologic and X-ray examination revealed no other
      abnormalities. The transaminase levels remained high after withdrawal of
      zidovudine alone, but a decrease was observed when both zidovudine and lamivudine
      were stopped. Rechallenge of lamivudine therapy caused the levels to increase
      again. The hepatic steatosis was considered to be caused by the antiretroviral
      therapy, lamivudine having a synergistic influence on this side effect of
      zidovudine. Ten months after the therapy was changed to the protease inhibitor
      indinavir combined with zalcitabine and stavudine, two other nucleoside
      analogues, hepatic steatosis recurred.

PMID- 9562779
TI  - [Enzyme inhibitors as drugs. III].

PMID- 9562780
TI  - [A little stress is not bad. A therapeutic perspective on stress proteins].

PMID- 9562781
TI  - [HIV-1 protease inhibitors in review].

PMID- 9562782
TI  - [Robert Koch Institute organized international expert circle for world-wide AIDS
      overwatch].

PMID- 9562783
TI  - [Instruction to authors:new requirements for manuscripts for publications in
      medical journals published by the National Institute of Hygiene: epidemiological
      review, experimental medicine and microbiology. Results of the state department
      of hygiene].

PMID- 9562784
TI  - [Subacute sclerosing panencephalitis (SSPE) in Poland in the years 1993-1995. The
      sixth stage of epidemiological research].
AB  - Data was collected about 49 newly diagnosed cases of SSPE in the years 1993-1995
      in Poland. In the analyzed period of time a falling of tendency the incidence of
      SSPE was maintained. Overall incidence--0.42 per million population, was lower
      than the incidence in years 1990-1992, when it was 0.72. The tendency of a shift
      towards older age group was maintained--the peak incidence was observed among 19
      year olds, as opposed to 15 year olds in the previous analyzed time period. The
      authors explain the dropping SSPE incidence in Poland with a drop in measales
      incidence, which is a consequence of growing measles vaccine coverage rates. The
      influence of a big measles epidemic which occurred in 1989-1990 on a potential
      rise in number of SSPE cases has not been noted, but further observations are
      needed.

PMID- 9562786
TI  - [Epidemiology of tuberculosis in Poland and in the world].
AB  - The paper describes the risk of tuberculosis infection and the incidence of the
      disease as measures of the epidemiological situation and presents data on the
      epidemiological situation of tuberculosis in Poland and the world. It also
      describes the effectiveness of the national tuberculosis control programme in
      Poland. The annual risk of tuberculosis infection in Poland is estimated at 0.2%
      which is about 10 times higher than the lowest one in Europe (the Netherland),
      but there are countries in the world with the risk of 2.0% and higher. The
      incidence of tuberculosis in Poland (all forms) declined from 182.6/100,000 in
      1965 to less than 40,0/100,000 in 1996, of which less than half were
      bacteriologically positive cases. The incidence of smear positive cases, the most
      infectious group, declined from 18.7/100,000 in 1980 to 9.7/100,000 in 1995. All
      cases of tuberculosis in Poland are treated with 4-drugs regimen in the intensive
      phase of treatment and 3-drugs in the continuation phase. The duration of
      treatment is 6-8 months and the cure rate is above 90%.

PMID- 9562785
TI  - [The outbreak of an epidemic of tick-borne encephalitis in Kielec province
      induced by milk ingestion].
AB  - Outbreak of tick-borne encephalitis (TBE) was reported between May 14 and June 20
      1995 in Busko Zdroj in Kielce Province. Drinking fresh (unboiled) goat's milk
      from private breeding was probable reason of the outbreak. 63 person drank goat's
      milk from the same source; 15 were hospitalized with neurological symptoms, 33
      persons had an influenza-like symptoms and were treated in out-patient department
      (27) or healed spontaneously (6), and 15 persons were healthy. TBE virus
      antibodies were found in CSF of all 15 persons with neuroinfection syndromes. IgM
      and IgG against TBE virus were present in sera of 15 hospitalized patients and 20
      patients with influenza like-syndromes. Antibodies to TBE virus were detected in
      serum of one of 19 goats from the breeding farm confirming the source of TBE
      virus infection.

PMID- 9562787
TI  - [Viral respiratory infections detected in small children in 1995-1996].
AB  - As in previous studies we used the fluorescent antibody technique to determine
      the aetiology of viral respiratory infections in small children who were
      hospitalized in the epidemic season 1995-96. Data obtained from this study were
      compared with the results from the previous season (1994-95) and with the results
      from preceding ten seasons (1985-95). No variation in aetiology of infections was
      found although a higher occurrence of adenoviruses was uncovered amongst the 1995
      1996 group. The monthly rates of morbidity in this same group were highest in
      November and in April. Data from this season displayed the greatest incidence of
      morbidity among children from one to six months old. The importance of bread
      feeding as a measure of prevention against viral respiratory infections was
      confirmed.

PMID- 9562789
TI  - [Passive and active immunoprophylaxis of hepatitis A. New vaccines].
AB  - The actually available methods of active and passive immunoprophylaxis of
      hepatitis A are presented against the background of hepatitis A epidemiology in
      Poland. The indications, dosage, immunogenicity, immunization schedules and
      effectiveness of inactivated vaccines are described.

PMID- 9562788
TI  - [Intestinal parasites in four Warsaw kindergarten children in 1994-1996].
AB  - In 1994/96 there were examined 588 children attending four Warsaw's
      kindergartens. Investigations were made by means of a standard coprological
      methods and by ELISA method for the presence of coproantigens of Giardia. The
      extensiveness of the infection was about 12.5%. It seems that now only oxyuriosis
      is the most important epidemiological problem among these children. The
      complexity of diagnosis and treatment of infected children and some health's
      education may improve their health and prevent the spreading of invasion.

PMID- 9562790
TI  - [Lyme borreliosis: emerging disease?].

PMID- 9562791
TI  - [Prevalence of Borrelia burgdorferi infection in Ixodes ricinus ticks at urban
      and suburban forest habitats].
AB  - The aim of this preliminary study was to estimate the risk of infection of Ixodes
      ricinus ticks by the agent of Lyme disease--Borrelia burgdorferi s.l. (Acari:
      Ixodidae). Ticks were collected from the vegetation during May--August 1996 at
      two different forest habitats: Dziekanow Lesny near Warsaw and Lasek Bielanski in
      Warsaw. Prevalence of B. burgdorferi infection of the nymphs and adults ticks was
      assessed by indirect immunofluorescence and polymerase chain reaction (PCR). Tick
      occurrence during time of sampling was greater in Lasek Bielanski than in
      Dziekanow Lesny. In both forest habitats ticks were infected with B. burgdorferi
      s.l., and prevalence of infection ranged from 19.2% in Lasek Bielanski to 31% in
      Dziekanow Lesny. Four species of B. burgdorferi s.l. were identified in the
      ticks: B. burgdorferi s.l., B. garinii, B. afzelii and group VS116. This study
      shows that suburban forest and urban park habitats where I. ricinus is present
      are risk areas of human infection with Lyme disease spirochaetes.

PMID- 9562792
TI  - [Incidence of Borrelia burgdorferi sensu lato spirochetes in Ixodes ricinus ticks
      from a museum collection evaluated by PCR].
AB  - Ixodes ricinus ticks (total n = 51:14 larvae, 16 nymphs, 17 females and 11 males)
      collected at 21 different sites during 1948-1987 were examined individually for
      the presence of Borrelia burgdorferi sensu lato spirochaetes. Detection of
      spirochaetes was carried out by polymerase chain reaction (PCR) using primers
      complementary to chromosomal sequence. Borreliae were found in 3 (3.56%) examined
      ticks (nymphs) collected at the same site (two in June, 1952 and one in August,
      1987). The low number of infected ticks found in this investigation do not
      reflects real infection rate in tick population.

PMID- 9562793
TI  - [Difficulties in diagnosis of lyme borreliosis].
AB  - A case of borreliosis in female aged 28 years is presented. Diagnosis was made
      late. The course of the disease was characterized by long-lasting high fever,
      enlargement of liver and spleen, pancreatitis, pneumonia of the left lung and
      anemia. During the antibiotic therapy (rocephin) neutropenia was observed. In
      every case of long-lasting fever of unknown origin, borreliosis should be taken
      into consideration.

PMID- 9562794
TI  - [Late consequences of untreated lyme borreliosis].
AB  - The study aimed to evaluate late clinical symptoms and serological changes in
      persons with erythema migrans (EM) diagnosed 4-11 years ago who were not treated
      with antibiotics. Among initially included into the study 28 untreated EM cases,
      twelve persons responded for invitation to the Department. The symptoms and signs
      which could be related to previous Borrelia burgdorferi infection were present in
      9 (75%) untreated patients. They included ischialgia (42%), arthritis (33%) and
      positive serological tests results (33% of patients, including 2 with clinical
      signs). These results demonstrate that lack of antibiotic treatment in the early
      LB stage can result in the development of late disease manifestations.

PMID- 9562795
TI  - [Changes in granulocytic receptors for FcR IgG and CR with circulating immune
      complexes in patients with lyme borreliosis].
AB  - This study aimed to estimate some PMN functions, involving phagocytic activity in
      patients with Lyme borreliosis. Decreased percentage PMN with FcR and CR
      receptors was observed. Increased immune complexes levels in the serum of
      patients before, and their normalization after treatment were found. These
      results indicate a depression of non-specific cellular response, which can
      influence the general immune system in patients with Lyme borreliosis.

PMID- 9562796
TI  - [Beta 2 microglobulin in children with neuroinfections].
AB  - CSF and plasma beta2 microglobulin (B2M) concentrations were determined by an
      enzyme linked fluorescent assay (ELFA) (Vidas-bioMerieux) in children with
      bacterial (B2M), viral (mumps and enteroviral) meningitis and in the controls.
      CSF B2M concentrations in children with B2M at admission, at 24-48 hrs of
      treatment and at recovery (day 10), in children with viral meningitis at
      admission and at recovery were significantly higher in comparison with the
      control group of children with non-pleiocytic CSF. The levels of CSF B2M at 24-48
      hrs of treatment of B2M cases were significantly higher than those at the
      beginning of both mumps and enteroviral meningitis cases which may be helpful in
      differential diagnosis of meningitis, especially in cases of retarded diagnosis
      or partially treated B2M. Plasma levels of B2M during bacterial and mumps
      meningitis did not differ from those in healthy children but in children with
      enteroviral meningitis were significantly higher. There was a positive
      correlation between CSF B2M at the beginning of B2M and some laboratory findings
      of inflammatory response (CRP, ERS). The CSF B2M levels were significantly higher
      than its plasma levels in patients with B2M at 24-48 hours (second stage) of
      disease, mumps meningitis on admission and recovery which may suggest intrathecal
      production of B2M during central nervous system infection.

PMID- 9562797
TI  - [Candida humicola infection of the central nervous system in an HIV-infected
      patient: a case report].
AB  - HIV infection and parenteral drug abuse are at increased risk of developing
      Candida infection. Central nervous system (CNS) infection is an exceptional
      finding. We present fatal CNS infection by Candida humicola in drug abuser at
      late stage of HIV disease. In MEDLINE we have found only 3 reports about
      pathogenicity Candida humicola in humans (ophthalmopathy, conjunctivitis,
      melanonychia). Our case report suggests, that spectrum of pathogens dangerous to
      persons with AIDS increases.

PMID- 9562798
TI  - [History of the Centers for Disease Control, Atlanta, USA].

PMID- 9562799
TI  - [Diagnosis of pertussis].

PMID- 9562800
TI  - [Candidiasis: an unrecognized problem].

PMID- 9562801
TI  - [Selected short-term bacterial and eukaryotic tests used for detection of
      genotoxicity of environmental chemical contaminants].
AB  - During the last years human exposure to environmental chemical contaminants
      (mutagenic/carcinogenic agents) has greatly increased. Evaluation of the
      biological effect of human exposure to mutagenic/carcinogenic agents in short
      term tests is very important. In present paper the bacterial and eukaryotic tests
      for detection of genotoxic effect of environmental chemical contaminants have
      been described.

PMID- 9562802
TI  - [Content of lead, cadmium,copper and zinc in hair of school children from
      selected rural areas in greater Lublin].
AB  - Contents of lead, cadmium, copper and zinc were determined in the hair of 164
      rural school children aged 7-15 years, by means of flame AAS method. The children
      attended four schools situated in the villages: Uhnin, Debowa Kloda, Urszulin and
      Debina. There were stated the lower contents of lead and zinc (1.84 and 101.1
      micrograms/g) and higher concentrations cadmium and copper (0.37 and 16.44
      micrograms/g respectively) in the children's hair from Debina, comparing to the
      other villages. The statistical analysis of the results revealed essential
      difference in the mean lead contents according to sex (more, in the boy's hair).
      There was considering the relationship between heavy metals levels in the hair of
      the children's population and their age as well as correlations between lead,
      cadmium, copper and zinc concentrations in the hair samples.

PMID- 9562803
TI  - [Analysis of soil pollution by polychlorinated biphenyls (PCBs) and heavy metals
      (Cd, Pb) along railroads near Ilawa Glowna].
AB  - The aim of our work was to investigate the soil pollution by PCBs at railway
      surroundings i.e. two railway lines and railway junction Ilawa Glowna. At railway
      junction the pollution by heavy metals (lead and cadmium) was also investigated.
      The soil samples collected on selected experimental areas were analysed by
      extraction and GLC. The results of our investigation allow to confirm the
      increased level of PCBs in analysed samples. It proves the suggestion about
      emission of PCBs connected with railway transport. The level of contamination is
      extremely high on the region of old railway junction Ilawa Glowna. The relation
      between type of carried load and level of pollution was not detected. The lack of
      close correlation between contamination level and distance from railway line may
      results from water unsolubility of PCBs. The concentration of PCBs depends mostly
      on transport frequency or train staying, whereas heavy metal concentration
      depends also from type of carried load.

PMID- 9562804
TI  - [Spectrophotometric determination of scandium,gallium and vanadium in white
      cabbage leaves].
AB  - Scandium, gallium and vanadium contents in plants is on the ppm level, although
      plants from industrial areas can show higher concentrations of these elements. In
      Department of Analytical Chemistry of Silesian University there have been
      elaborated new, sensitive, spectrophotometric methods of determination of
      scandium, gallium and vanadium using Chrome Azurol S (CAS) and Sterinol (ST). The
      aim of this study was the application of these methods in analysis of cultivated
      plants from polluted regions. White cabbage from Upper Silesia was chosen.
      Because the spectrophotometric methods are not selective, scandium, gallium and
      vanadium should be preliminary separated from interfering elements. The solvent
      reaction was applied for the isolation from main and trace components of
      investigated material. Tienoiltrifluoracetone solution in xylene was used for the
      extraction of scandium, mesithyloxide for vanadium and n-butyl acetate--for
      gallium. Interfering and not separated Fe(III) was isolated using the extraction
      with acetylacetone solution in CHCl3 in the case of scandium and the reduction to
      Fe(II) by ascorbic acid in the case of gallium and vanadium. Due to influence of
      Fe(II) on the vanadium determination, KCN was used as a masking agent directly
      after the reduction. Scandium, gallium and vanadium were determined in 6
      independent samples of white cabbage after dry or wet mineralization and contents
      of these leemnets were found from calibration graphs. Obtain results were checked
      by the internal standard addition method and Atomic Emission Spectrometry Method
      (ICP AES). The amounts of gallium and vanadium in white cabbage from Upper
      Silesia District determined by elaborated methods are in good correlation with a
      literature data, although the contents of vanadium are on the toxic level. The
      scandium concentration is higher than in plants from not industrial areas. The
      standard recovery is satisfactory. The Atomic Emission Spectrometry Method gave
      comparable results. The proposed the spectrophotometric methods are sensitive,
      precise and economical too, because they require only small amounts of reagents
      and simple not expensive apparatus. The methods can be recommended for many
      laboratories to the analytical control of white cabbage and after adaptation to
      the other plant material analysis.

PMID- 9562805
TI  - [Determination of antibiotic residues and other inhibitors in milk--quality
      assurance system].
AB  - In the methods used widely for the determination of antibiotic residues in food
      product of animal origin the antibiotic-sensitivity of microorganisms is used. An
      advantage of microbiological methods is their high detection rate, but they are
      not specific. The test strains are not selectively sensitive and are inhibited by
      many antibiotics. False positive results of these tests may be due to the
      presence in tissues or milk of natural substance, e.g. enzymes or compounds of
      external origin--detergents or other drugs, e.g. sulphonamides. The
      microbiological tests--plate and tube STD and Polutest, as well as the enzymatic
      Penzym test, all recommended in the Polish Standards PN-91/A-86033 for milk
      control for the detection of antibiotic residues were compared. The authors
      describe the requirements to be met by the systems of quality ensuring during
      determination of antibiotics and other inhibitors in milk. The requirements to be
      met by the methods of this determination are discussed, together with the
      principles of intralaboratory and interlaboratory quality controls.

PMID- 9562806
TI  - [Activity of the Codex Alimentarius Commission FAO/WHO on quality assurance in
      the laboratory].
AB  - The activity of the Codex Alimentarius Commission FAO/WHO concerning the quality
      assurance in laboratory was discussed. Major documents issued by the joint
      efforts of the international organizations (IUPAC, ISO, AOAC Int.) and Codex
      Alimentarius FAO/WHO Committee on Methods of Analysis and Sampling (CCMAS) are
      also presented in the article. The basic task of the CCMAS is reviewing and
      harmonization of the international documents in order to make them available for
      food analytical laboratories and to recommend the internationally recognised
      approaches for: collaborative studies--Protocol for Design, Conduct and
      Interpretation of Method-performance Studies. Pure & Appl. Chem. 1995, vol. 67,
      332-343 proficiency testing--The International Harmonized Protocol for the
      Proficiency Testing (Chemical) Analytical Laboratories. Pure & Appl. Chem. 1993,
      Vol. 65, 2123-2144 and J.AOAC Int. 1993, Vol. 76, 926-940 internal quality
      control (IQC)--Harmonized Guidelines for Internal Quality Control in the
      Analytical Chemistry Laboratories. Pure & Appl. Chem. 1995, Vol. 67, 650-666
      determining and use of recovery factor--Harmonized Protocol for Recovery Factor
      in Analytical Measurements--document CX/MAS 97/6 applicability of the measurement
      uncertainty--Measurement Uncertainity--document CX/MAS 97/7.

PMID- 9562807
TI  - [Unsaturated fatty acids omega-3. I. Structure, sources, determination,
      metabolism in the organism].
AB  - Fats covered approximately 22% of energy requirements in diets of ancient human
      being, and simultaneously the value of ratio of polyunsaturated fatty acids
      (PUFA) to saturated (SFA) was estimated as 1.4 and the proportion of PUFA omega 6
      to PUFA omega 3 was 1:1. During the last twenty thousands years the composition
      of human diets was changing dramatically due to economical, culture and social
      changes. However, there are indicators that the ratio of PUFA omega 6 to PUFA
      omega 3 in human diet was unchanging until beginning of XIX century. Dramatic
      technological breakthrough in food technology during last 100 years caused
      radical changes in the structure and quality of food consumption. It is estimated
      that at present fats cover about 40% of energy requirements in diets of people in
      developed countries, and the value of ratio of dietary PUFA omega 6 to PUFA omega
      3 is 25:1 and even 50:1. Epidemiological nutritional studies indicate that in
      populations which consume inadequate amount of PUFA omega 3 most often occur the
      disorders on atherosclerotic and immunological background as compared to
      populations which consume diets with appropriate covering the requirements of
      dietary PUFA omega 3. Therefore, it could be supposed that increased occurrence
      so-called civilization disorders is the result of increased consumption of highly
      manufactured food with changed composition (and also to increased fats
      consumption and decreased consumption of PUFA omega 3). This hypothesis is
      confirmed by the observations that the supplementation of diets with PUFA omega 3
      gives the desirable results in the treatment of many disorders. The main
      objective of this two parts paper is to characterize the polyunsaturated fatty
      acids, their metabolic path ways as well as the possibilities of the use of the
      diet supplementation with PUFA omega 3 in the treatment and prophylaxis of some
      metabolic disorders. The structure, sources, determination and pathways in
      organism are discussed in part I, and the role of eicosanoids originating from
      respective PUFA omega 3 and advantages of the supplementation the diet with PUFA
      are discussed in part II.

PMID- 9562808
TI  - [Evaluation of the usefulness of vitamin/mineral preparations as dietary
      supplements].
AB  - The purpose of this work was to evaluate the vitamin/mineral preparations
      available on Polish market in 1995 in relation to their usefulness as dietary
      supplements. On the basic of the information in compendia, scientific papers,
      booklets, leaflets etc. the catalog of products containing vitamins and/or
      minerals was prepared. Complete data on composition, designation and other
      descriptors of 274 products were included. For further 28 preparations no full
      data were available. More than 53% of preparations were produced in Poland. Out
      of 274 preparations, 50% contained a single nutrient, while 20.1% contained 2-5
      nutrients, 14.6%--from 6 to 10 nutrients, 13.1%--from 11 to 20 and only 2%--from
      21 to 30 nutrients. Most of the products were intended for adults (165
      preparations), adolescents (154 preparations) and children (132 preparations).
      Only 16 products were designed for pregnant and lactating women. Some of the
      preparations were intended for more than one population group with different
      dosage recommended by the producer. The amounts of nutrients in a single unit
      (pill, tablet etc.) of each product as well as percentage of recommended daily
      intake were estimated. Generally, these amounts were higher in products
      containing single nutrient than in multivitamin/mineral preparations. Out of 274
      products included into the catalog, 132 met criteria established for dietary
      supplements in Poland (i.e. the amount of nutrients in supplements should not
      exceed 150% RDA). Among them in 25 preparations the amounts of nutrients in a
      unit of product were in agreement with a definition of supplements but daily
      doses recommended by the producers were much higher than 150% of RDA. For 33
      products the amounts of nutrients in single units were very low, therefore to
      obtain a dose significant for dietary supplementation, one should take several
      units per day, usually the maximal dose recommended by producer. For 74
      preparations the amounts of nutrients in single units as well as in daily doses
      recommended by the producer met criteria for supplements. Lack of complete and
      clear information on the label of vitamin/mineral preparations as well as lack of
      data on percentage of RDA covered by nutrients in the unit of product are the
      most important difficulties in choosing for dietary supplementation. The
      knowledge of composition of preparations containing various nutrients is
      necessary for nutritionist who want to assess the intake and nutritional status
      of some individuals as well as for their counselling work.

PMID- 9562809
TI  - [Composition of nutrients and minerals in some goat milk products].
AB  - The paper contains results of determinations of protein, fat, carbohydrates,
      water and minerals (Ca, P, Fe, Mn, Cu, Zn, Na, K) in 12 goat milk products. The
      nutrient components were determined by general approved analytical methods.
      Minerals like Ca, Fe, Mn, Cu, Zn, Na and K were determined by the flame ASA
      method. Phosphorus was determined as phosphates by colorimetric method with
      ammonium molybdate. Mean percentage content of protein, fat, carbohydrates and
      water were: 9.7-25.7; 1.4-33.5; 2.2-70.2; and 3.0-77.4 respectively. The content
      of minerals according to the products of goat milk were as follow: 86-1113 mg%
      Ca; 96-846 mg% P; 0.2-2.4 mg% Fe; 6-148 mg% Mg; 0.002-0.284 mg% Mn; 0.071-0.754
      mg% Cu; 1.1-3.9 mg% Zn; 63-1281 mg% K and 27-407 mg% Na. The levels of nutrients
      and mineral composition of the examined goat milk products were similar to that
      of the cows milk products.

PMID- 9562810
TI  - [The effect of water pipelines on the quality of drinking water].
AB  - The purpose of the study was to assess the effects of various pipelines on
      drinking water quality. For the study carried out in Warsaw buildings were chosen
      in which the installations were made of polypropylene, polyvinyl chloride, copper
      and steel. Water samples were taken from the sites of water leading to the
      buildings and from the highest floors, if possible. Physicochemical studies
      included determination of turbidity, colour, odour, pH, hardness, chlorides,
      ammonia, nitrates, nitrites, oxidation, manganese, iron, lead, cadmium, copper
      and zinc content. Bacteriological tests included determination of total
      microorganism count at 20 degrees C and 37 degrees C, total number of sporing
      bacteria and Pseudomonas aeruginosa. The hydro-biological testing of water
      samples included quantitative and qualitative analysis of macroscopic and
      microscopic plant and animal organisms. All studies were carried out according to
      Polish Standards and the methods of the State Institute of Hygiene. The results
      of the physicochemical, bacteriological and hydro-biological tests failed to show
      any effect of the material of pipelines on the quality of drinking water in the
      range of the determined parameters.

PMID- 9562811
TI  - [Hair colorants].
AB  - The properties, mode of action and its duration of the preparations used for hair
      dyeing are described, together with their chemical components, and also
      preparations of herbal origin. The chemical reactions are described in detail
      which lead the development of a color polymer occurring during hair dyeing. The
      studies are presented which are used for toxicological assessment of the raw
      materials which are the components of the colorants, and the list is included of
      hair colorants permitted for use in Poland.

PMID- 9562812
TI  - [Thyroid gland carcinoma].
AB  - Carcinoma of the thyroid is a rare tumour, comprising approximately 1% of human
      malignancies. Thyroid carcinoma is classified according to its origin (thyroid
      follicular cell or calcitonin-producing C cell) and grade of differentiation
      (differentiated, poorly differentiated or anaplastic). Due to their different
      biology, genetical background and clinical course, which result in fundamentally
      different therapeutic strategies, the various types of thyroid carcinoma have
      attracted a lot of interest by both clinicians and pathologists. This review
      article deals with the most important aspects (definition, epidemiology, clinical
      course, prognosis, differential diagnosis and genetic background) of the various
      thyroid carcinomas.

PMID- 9562813
TI  - [Diagnosis, radioiodine and radiotherapy of thyroid carcinomas].
AB  - The long-term prognosis of differentiated thyroid carcinoma depends on early
      diagnosis and treatment of metastases and local recurrences and is modulated by
      several factors, age and histology being the most relevant. This article
      summarizes current trends in the use of radioactive iodine (131J) and gives
      explicit advice on its use in the treatment of these cancers. Complications of
      therapy are discussed in detail. We currently recommend that all patients
      undergoing a subtotal or total thyroidectomy are followed up by 131J thyroid
      scanning approximately 4 weeks after surgery. The combined use of three
      diagnostic modalities (measurement of serum thyroglobulin, neck ultrasonography
      with ultrasound-guided biopsy for detecting recurrences of carcinoma in the neck
      region and 131J whole-body scintigraphy) appears to give the best results in the
      follow up of patients with differentiated thyroid carcinoma. If any residual
      uptake is detected in the neck or if the tumor extends beyond the thyroid, we
      recommend routine thyroid ablation with 1,5-3 GBq of radioactive 131J. External
      radiotherapy is always indicated in papillary and folliculary carcinoma in the
      pT4 stage of pTNM classification but not in those in pT1-3 pN0 stage. In the
      presence of lymph-node metastases and distant metastases, an individual treatment
      concept is recommended regarding all risk factors, especially the age and sex of
      the patient, the histology and grading of the tumor and the completeness of tumor
      resection. Finally, radiotherapy is usually not indicated in medullary carcinoma,
      whereas it is always indicated in anaplastic carcinoma.

PMID- 9562814
TI  - [From limited to extensive radical operation in thyroid carcinoma].
AB  - The incidence of malignant thyroid tumors in Germany is about 1-2 cases per
      100,000 inhabitants and year with a preponderance of female to male 3:1. Thus
      malignant thyroid tumors are rare and account for about 0.5% to 1% of all
      malignancies. Special consideration, however, has to be paid to the fact, that
      thyroid lesions associated with the risk of malignancy are much more frequent.
      Therefore identification of patients with particular risk for thyroid malignancy
      out of the 15% to 20% of the German population with thyroid lesions has to be the
      main scope. Prognosis of differentiated thyroid carcinomas is excellent and
      requires operative procedures adapted to histological tumor type and tumor stage.
      Hemithyroidectomy for small papillary tumors can be as adequate as total
      thyroidectomy including bilateral neck dissection plus mediastinal lymph node
      dissection in medullary thyroid carcinoma. Generally radical resection of tumor
      is the aim. Palliative modalities in distant metastatic disease or
      undifferentiated tumors are indicated to optimize additive or adjuvant therapy
      resp. to improve prognosis.

PMID- 9562815
TI  - [Endocrine therapy and after-care in thyroid gland carcinoma].
AB  - The 10 year survival is excellent for stage I disease thyroid carcinoma. Survival
      decreases as a function of cancer invasion beyond the gland. Papillary and
      follicular cancers have longterm survival, but anaplastic cancers are lethal and
      survival is short. In differentiated carcinomas thyroidectomy and neck dissection
      are followed by radioiodine therapy to eliminate residual tissue and metastases.
      In case of papillary microcarcinomas a limited resection is justified. There is
      no need for radioiodine treatment. Thyroid hormones are given postoperatively in
      a high dose to suppress TSH. An increase of the tumor marker thyreoglobulin
      indicates the development of relapse or metastases. In medullary carcinoma basal
      or serum calcitonin levels after stimulation with pentagastrin-elicited are
      pathognomonic for a relapse. 25% of the medullary thyroid carcinomas are observed
      in families. Genetic screening is mandatory in patients with medullary carcinoma.
      Serum calcium values should be controlled to exclude safely hypoparathyroidism
      with certitude.

PMID- 9562816
TI  - [From reposition to stabilization--on the history of shoulder instability].

PMID- 9562817
TI  - [Clinical examination of the shoulder].
AB  - The clinical examination is decisive in the diagnosis of shoulder pathologies.
      This examination should be exact and systematic and in relation with the
      anatomical structures. With patient history, the clinical examination allows in
      over 90% of the cases a correct diagnosis. Complementary exams such as standard X
      rays, CT-Scan, MRI and neurological examinations serve to confirm the diagnosis
      and to allow precise surgical planning.

PMID- 9562818
TI  - [Imaging methods].
AB  - A number of abnormalities of the shoulder joint can cause pain or dysfunction.
      Imaging of this complex joint is demanding. Standard radiographs are considered
      to represent the basis of all imaging. For more detailed diagnoses, especially
      concerning soft tissue, more advanced imaging methods are required. Standard
      arthrography (without combination with either CT or MRI) is rarely indicated
      anymore. Bone scintigraphy is another imaging method with limited use in shoulder
      joint abnormalities (neoplasm, infection, occult fracture). Sonography is useful
      in abnormalities of the rotator cuff and the biceps tendon. This method is
      commonly employed for screening. CT is useful in the demonstration of complex
      fractures. CT arthrography is indicated in instability of the glenohumeral joint
      and is competing with MR arthrography. MRI and MR arthrography are the imaging
      method of choice for many indications, mainly due to their free choice of imaging
      planes and excellent contrast resolution. These methods provide the most detailed
      diagnosis mainly with regard to abnormalities of the rotator cuff (partial versus
      intact or full-thickness tears) and the biceps tendon and are useful in the
      assessment of instability.

PMID- 9562819
TI  - [Current status of shoulder arthroscopy].
AB  - Arthroscopic and open shoulder surgery have to be combined for a successful
      surgical therapy of the shoulder joint. A surgeon performing open surgery only or
      just treating by arthroscopic measurements can not cover the full spectrum of
      modern shoulder surgery. Isolated diagnostic arthroscopy is rarely indicated. Far
      more common, diagnostic arthroscopy is combined with an operative procedure both
      to confirm preoperative assessment of pathology and to uncover associated
      lesions. The results of arthroscopic stabilisation of chronic anterior
      posttraumatic dislocations fail to compare with high success rates of open
      procedures. Better patient selection will probably be the key to improving
      results. In case of acute traumatic first time dislocation in young highly
      sportive athletes the arthroscopic repair of the isolated Bankart-Perthes lesion
      offers the attractive advantage of anatomic reconstruction with minimal soft
      tissue dissection. Further indications for arthroscopic measurements of
      pathologies of the glenohumeral joint are synovectomy in rheumatoid arthritis,
      capsulotomy of shrunk capsule in frozen shoulder and tenodesis for lesions of the
      long head of the biceps. The arthroscopic subacromial decompression according to
      Ellman is the most often and successful performed procedure at the shoulder joint
      and has overcome the classic Neer open acromioplasty. For smaller tears of the
      supraspinatus tendon the arthroscopic acromioplasty can be combined with an all
      arthroscopic suture repair or with an mini-open repair. Larger tears of the
      rotator cuff are still the domain for open reconstructive procedures. In case of
      associated or isolated AC-joint arthritis an arthroscopic Mumford procedure can
      be performed. For chronic calcific tendinitis isolated arthroscopic excision of
      the calcium deposit is of great value. Additionally, acromioplasty is needed for
      true mechanical obstruction of the subacromial space.

PMID- 9562820
TI  - [The first dislocation of the shoulder].
AB  - The classical anterior-inferior dislocation of the shoulder is diagnosed easily
      by clinical examination and x-ray. The additional lesions like impression
      fracture at the humerus, avulsion of the anterior rim of the glenoid, lesions of
      the rotator cuff or neurologic deficits are more difficult to realise. In young
      patients the redislocation rate is rather high. Indication for surgery is still
      on debate. Modern diagnostic tools will help to determine additional lesions.
      More problems are incountered in presence of a posterior dislocation. Those are
      often overlooked.

PMID- 9562821
TI  - [Classification and therapy of the unstable shoulder].
AB  - Instability of the shoulder can be classified as uni- or multidirectional with or
      without general hyperlaxity. Instability of a shoulder without hyperlaxity is
      often caused by a single traumatic event for the unidirectional instability and
      by two or several different events for the rarer multidirectional instability.
      The diagnosis of unidirectional instability is made with a positive apprehension
      test. For multidirectional instabilities, the anterior and posterior apprehension
      tests are positive. The treatment consists of surgical repair of the labrum
      capsule complex for both the uni- and the multidirectional instabilities without
      hyperlaxity. For shoulders with a concomitant hyperlaxity, uni- or
      multidirectional instability is often caused by only minor trauma. Hyperlaxity
      itself is not a disease but represents a risk factor of instability. The typical
      feature of hyperlaxity is the positive "sulcus sign". Unidirectional instability
      with hyperlaxity is characterised by a positive apprehension test combined with a
      positive sulcus sign. Multidirectionally unstable shoulders with hyperlaxity have
      a positive anterior and posterior apprehension test as well as a positive sulcus
      sign. The unidirectional instability with hyperlaxity is best treated surgically
      whereas conservative treatment is recommended for the multidirectional
      instability with hyperlaxity. The voluntary instability without loss of control
      of position of the shoulder is not a real instability and has an excellent
      prognosis without treatment.

PMID- 9562822
TI  - [Osteosynthesis of proximal humerus fractures].
AB  - Only 5% of adult fractures are fractures of the proximal humerus. In 80% of these
      fractures one can expect a good result, because they are generally nondisplaced,
      stable and allow early mobilization. However, the other 20% of these fractures
      present not only problems with reduction and adequate fixation but also the risk
      of humeral head necrosis and painful shoulder ankylosis. The operative treatment
      of displaced fractures of the proximal humerus has changed during the last few
      years. Minimal osteosynthesis takes into consideration the great extend and the
      biological aspects of these fractures and provides sufficient stability for early
      functional therapy. The Neer-classification has proved very useful for both, the
      indication for and the choice of an operative procedure.

PMID- 9562823
TI  - [Indications and results of shoulder prosthetics in complex proximal humerus
      fractures].
AB  - Complex fractures of the proximal humerus are uncommon injuries and a therapeutic
      challenge to the orthopaedic surgeon. Successful treatment requires proper
      evaluation of the patient and analysis of standardized high-quality radiographs.
      The trauma series of radiographs (including true anteroposterior and lateral
      views in the scapular plane, and axillary view) is essential for accurate
      fracture assessment. Generally, joint-preserving reconstructive techniques are
      emphasized, aiming at restoration of the anatomy of the proximal humerus. In
      young individuals with excellent quality of the bone fragments, careful
      techniques of reduction and fixation, avoiding additional surgical
      devascularization, should be performed, even in case of possible impairment of
      the vascular supply to the humeral head. In elderly individuals with osteoporotic
      bone and limited compliance throughout aftercare, humeral head replacement may be
      indicated less restrictively. In the latter group hemiarthoplasty generally can
      be expected to result in painfree shoulders. However, recovery of function and
      range of motion are much less predictable.

PMID- 9562825
TI  - [Rotator cuff rupture: definition, establishing the diagnosis and therapy].
AB  - The rotator cuff tear is an extremely common disorder in the general as well in
      the orthopaedic praxis. The etiology is multifactorial with intrinsic and
      extrinsic factors. Clinical assessment of the patient is important for an exact
      diagnosis and an individual treatment plan. The treatment options of full
      thickness tears include conservative as well as operative procedures. Over the
      last years, modified techniques have improved the results of rotator cuff
      reconstruction.

PMID- 9562824
TI  - [Indications for shoulder prosthetics in degenerative and inflammatory diseases].
AB  - Shoulder arthroplasty has since it's more widespread introduction in the early
      seventies found a general acceptance as an excellent tool for treating late stage
      arthritis of the shoulder joint. The indications will vary from primary
      osteoarthritic disease to inflammatory diseases such as rheumatoid arthritis, or
      psoriatric arthritis. It is also used as a primary tool in multifragmented
      shoulder fractures, which can not be restored anatomically, or are felt at risk
      for avascular necrosis. The surgeon setting out for this procedure has to decide
      whether a total arthroplasty is required in cases with glenoid destruction, or at
      risk of developing secondary degenerative changes in the glenoid early on. A
      hemiarthroplasty will only replace the humeral side of the joint, but while well
      accepted in the fracture patient, the arthritic patients tend to fare better with
      a total joint replacement for pain relief.

PMID- 9562826
TI  - Antibiotic resistance and prescribing practices.

PMID- 9562827
TI  - Intermittent chest pain in a 77-year-old man.

PMID- 9562828
TI  - Angiotensin II receptor blockers in hypertension and renal disease.

PMID- 9562829
TI  - Atypical chest pain: a typical Humpty Dumpty term.

PMID- 9562830
TI  - Sick transit....

PMID- 9562831
TI  - The Nibelungen Sitzfleisch syndrome: a new clinical entity?

PMID- 9562832
TI  - Case in points. Secondary syphilis.

PMID- 9562833
TI  - Complications following tube gastrostomy.

PMID- 9562834
TI  - Screening and early intervention for COPD.
AB  - Chronic obstructive pulmonary disease is on the increase. Therapeutic improvement
      is limited by the irreversible nature of lung tissue loss. Basic lung function
      tests can detect early loss of function, which may facilitate smoking cessation
      and other interventions likely to delay disease progression. The advent of
      inexpensive portable spirometers promises to permit such testing in the primary
      care physician's office.

PMID- 9562835
TI  - AIDS-associated Kaposi's sarcoma.
AB  - In less than two decades, the disease mechanisms have been elucidated and
      hypotheses for innovative treatment have been developed. Our understanding of the
      sarcoma's pathogenesis has led directly to general knowledge of the physiology
      and pathology of angiogenesis. Hence, it can be expected that new treatments for
      all cancer patients may someday emerge from clinical intervention trials for the
      AIDS-related disease.

PMID- 9562836
TI  - SLE: mechanisms of vascular injury.
AB  - The chronic elevation of complement split products seen in many patients with
      systemic lupus erythematosus should be regarded as equivalent to silent
      hypertension, or hyperglycemia in a patient with incipient diabetes mellitus.
      Although the consequences may not be immediately evident, such patients should be
      monitored and perhaps even treated.

PMID- 9562837
TI  - Familial Mediterranean fever: the genetics of inflammation.
AB  - When a patient complains of episodic fever accompanied by unexplained arthritis,
      peritonitis, pleurisy, or skin rash, this disorder should be considered. The
      disease-related gene codes for a protein that guides a neutrophil's participation
      in inflammation; the protein's existence implies an entire regulatory pathway
      hitherto unknown. At least two other mendelian periodic fever syndromes have also
      been described.

PMID- 9562838
TI  - The illiterate patient: screening and management.
AB  - Illiteracy, which affects about 22% of adults in the United States, can hamper
      patient communication, treatment, compliance, and access to care. Alternative
      communication methods and active screening for illiteracy are crucial to
      addressing this problem.

PMID- 9562839
TI  - Management of precocious puberty.

PMID- 9562840
TI  - Evaluation and treatment of elbow pain.

PMID- 9562841
TI  - A young woman with anemia.

PMID- 9562842
TI  - A boy with headache, fatigue, and weakness.

PMID- 9562843
TI  - Abdominal pain in an alcoholic.

PMID- 9562844
TI  - Respiratory failure in a man with bone and lung lesions.

PMID- 9562845
TI  - [The beta blocker Betaxolol--a significant alternative in hypertension therapy].

PMID- 9562846
TI  - [Topiramat in childhood epilepsy. A growing indication spectrum in everyday
      clinical practice. 2nd Congress of the European Pediatric Neurology Society,
      Maastrich, 9 October 1997].

PMID- 9562847
TI  - Cumulative subject index. Volumes 263, 264, 266-289.

PMID- 9562848
TI  - [Schizophrenia and quality of life--therapeutic objectives to be re-defined].

PMID- 9562849
TI  - [Primary and secondary surfactant deficiency: implications for therapy. Satellite
      symposium: 23rd annual convention of the German-Austrian Society for Neonatology
      and Pediatric Intervention-medicine, Munster, 17 October 1997].

PMID- 9562850
TI  - [A differentiated contrast medium in interventional cardiology. Strategy for the
      reduction of thromboembolic complications].

PMID- 9562851
TI  - [Fosamax--newest scientific findings. Prague, 14 November 1997].

PMID- 9562852
TI  - Hepatitis G virus (GBV-C) infection among Brazilian patients with chronic liver
      disease and blood donors.
AB  - BACKGROUND: The recently discovered hepatitis G virus (HGV) belongs, as hepatitis
      C virus (HCV), to the Flaviviridae family. HGV has been isolated from the serum
      of patients with non A-E hepatitis. However, the association of HGV with
      hepatitis is uncertain. OBJECTIVE: To determine the HGV prevalence in blood
      donors and in patients with liver disease and to evaluate a possible correlation
      between HGV infection and liver disease. STUDY DESIGN: Sera from a total of 113
      consecutive patients with chronic liver disease were submitted to a series of
      liver enzymes and function tests and analyzed for the presence of HBsAg, anti
      HBs, anti-HBc, anti-HCV, HCV RNA and HGV RNA. Prevalence of HGV RNA was
      determined in a group of 87 blood donors. RESULTS: Nine (10%) sera from blood
      donors and 15 (13%) sera from patients with chronic liver disease were HGV RNA
      positive. Some 28 (25%) patients were HCV RNA positive, with genotypes 1a, 1b and
      3 present in 10, 12 and 5 patients, respectively. A total of 20 (18%) patients
      were HBsAg carriers. Five (4%) patients were double infected (one with HBV + HCV,
      one with HBV + HGV and three with HCV + HGV). CONCLUSION: The proportion (10%) of
      HGV-infected blood donors was very high when compared with other countries. The
      results did not allow to establish HGV as an etiologic agent for chronic liver
      disease. The parenteral route was the presumed means of HGV transmission for only
      one-third of the patients.

PMID- 9562853
TI  - Avidity of IgG antibodies distinguishes primary from non-primary cytomegalovirus
      infection in pregnant women.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) is the most common cause of viral
      intrauterine infection. Fetal damage is mostly linked to maternal primary
      infection. It is therefore important to differentiate primary from non-primary
      infection in pregnant females. IgM tests often used for this purpose are not
      reliable enough. OBJECTIVE: To evaluate an HCMV-IgG urea-elution assay for its
      ability to distinguish primary from non-primary infection. In this assay, soaking
      the antigen-antibody complex with an urea containing solution frees antibodies
      with low avidity but has no influence on those with high avidity. An avidity
      index (AI) was calculated: AI = (OD with urea/OD without urea) x 100. STUDY
      DESIGN: HCMV-IgG avidity was measured on a single serum of 79 patients with past
      infection (pregnant women, graft recipients and blood donors) and of 63 patients
      (78 sera) with documented seroconversion (pregnant women and graft recipients).
      Sixty-one pregnant women positive or equivocal for HCMV-IgM but without a
      documented seroconversion were included in this study. RESULTS: Most (72/79) of
      the patients with past infection had an AI > 65% and all but one had an AI > 50%.
      In pregnant women, in the case of a primary infection within the past 3 months,
      AI are usually (51/53) < 50% and never > 65%. Among the IgM positive pregnant
      women who lack a seroconversion history, 38 had AI > 65% suggestive of an
      infection that had occurred at least 3 months earlier, 11 had an AI in a grey
      area between 50 and 65% and 12 had an AI < 50%, suggestive of a recent primary
      infection. CONCLUSIONS: In pregnant women, measurement of the IgG avidity may
      help to date a HCMV infection, an AI > 65% highly suggests a past infection while
      an AI < 50% corresponds to a recent primary infection.

PMID- 9562855
TI  - Introduction of HIV-1 subtypes C, E and A into Austria.
AB  - BACKGROUND: Different subtypes of HIV-1 are prevalent in various geographical
      regions. Knowledge of their distribution is of importance with respect to
      possible differences in biological properties (such as reported for subtype E) as
      well as to diagnostic problems that may arise when specific subtypes are not
      recognized by standard serological assays. OBJECTIVES: The objectives of this
      study were to investigate the presence of the five major subtypes of HIV-1 (A-E)
      in the Austrian population and to estimate the prevalence of the individual
      subtypes in different risk groups. STUDY DESIGN: Serum samples from 88 HIV-1
      positive patients were tested for the presence of subtype-specific antibodies
      using a peptide ELISA. RESULTS: The majority of the patients were shown to be
      infected with HIV-1 subtype B, but infections with subtypes A, C, and E were also
      detected in the Austrian population, primarily in the heterosexual transmission
      group. While subtypes A and C were probably imported from different African
      countries, subtype E appears to have been introduced by sex tourists returning
      from Thailand. CONCLUSION: Introduction of HIV subtypes other than B from Africa
      and Asia into Austria has already occurred and will certainly increase within the
      next few years.

PMID- 9562854
TI  - Molecular detection and isolation of human T-cell lymphotropic virus type I (HTLV
      I) from patients with HAM/TSP in Sao Paulo, Brazil.
AB  - BACKGROUND: Infection with HTLV-I is etiologically linked with HTLV-I-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). However some patients with
      chronic progressive paraparesis resembling HAM/TSP have been shown to be infected
      with HTLV-II. OBJECTIVE: To clarify the role of each of these human retroviruses
      in the etiology of HAM/TSP in Sao Paulo, Brazil. STUDY DESIGN: A detailed
      serological and molecular analysis of HTLV-I/II infection was performed in a
      cohort of 19 patients with HAM/TSP attending a neurological clinic. RESULTS:
      Plasma samples analyzed for anti-HTLV-I/II antibodies using a Western blot assay,
      comprising HTLV-I (rgp46I)- and HTLV-II (rgp46II)-specific recombinant env
      epitopes, demonstrated reactivity to rgp46I and hence were typed as seropositive
      for HTLV-I. Presence of HTLV genomic sequences in peripheral blood mononuclear
      cells (PBMC) was sought after by PCR using consensus primers SK 110 and SK 111
      for the pol region of HTLV proviral DNA followed by hybridization with type
      specific probes--SK 112 (HTLV-I) and SK 188 (HTLV-II). Southern blots from all
      individuals hybridized with SK 112 but not with SK 188, further confirming HTLV-I
      infection. Cocultivation of PBMC from eight of these patients with activated
      lymphocytes from normal individuals resulted in active viral production, detected
      as presence of soluble p24gag antigen in culture supernatants. Investigation of
      risk factors for HTLV-I infection in these individuals revealed that five out of
      19 patients studied (26.3%) had received blood transfusions previous to disease
      onset.

PMID- 9562856
TI  - Prevalence of infection with HIV, hepatitis B and C viruses, in four high risk
      groups in Eritrea.
AB  - BACKGROUND: Little is known about the prevalence of infections in different
      population groups in Africa, and about the influence of living conditions on the
      spread of infections. This study is the first of its kind in the state of Eritrea
      and is expected to serve as an evaluation of the situation in the country.
      OBJECTIVE: A serosurvey for human immunodeficiency virus (HIV), hepatitis B virus
      (HBV) and hepatitis C virus (HCV) was carried out during the summer of 1995 in
      Massawa, a small sea port in Eritrea (East Africa) in four groups considered to
      be at risk for these infections. STUDY DESIGN: The study subjects were former
      Guerrilla Fighters, Female Sex Workers, Truck Drivers, and Port Workers.
      Participants from a tribe called Rashaida were believed to be at low risk, and
      thus served as a control. RESULTS: The Female Sex Workers had the highest
      incidence of HIV-1 infection, 29%, compared to 10% for Port Workers, and 3% for
      Guerrilla Fighters. On the other hand presence of HBsAg, indicating a high
      prevalence of hepatitis B carrier status, was highest in the Guerrilla Fighters,
      followed by the Rashaidas, and lowest in the Female Sex Workers. The Female Sex
      Workers were further tested for antibodies against HBV and the results revealed
      that 53% of them, 5%, had antibodies against HBcoreAg. Excluding the possibility
      of an acute infection at sampling time, three of them became HBsAg carriers.
      Surprisingly, our group of Truck Drivers did not show HIV-1 infection, and no HIV
      2 infections were seen in the whole cohort. CONCLUSION: The study shows that the
      described groups have different prevalences of infection with HIV, hepatitis B
      and C which can partly be explained by their living conditions.

PMID- 9562857
TI  - Evaluation of a new assay for HBV DNA quantitation in patients with chronic
      hepatitis B.
AB  - BACKGROUND: The Amplicor HBV Monitor Test for quantitative determination of serum
      hepatitis B virus (HBV) DNA has recently been introduced. This assay is based on
      PCR and a non-radioactive hybridization and detection system on microwell plates.
      OBJECTIVE: The performance of the Amplicor HBV Monitor Test was evaluated in a
      routine diagnostic laboratory. The Amplicor HBV Monoitor assay was compared to
      the Digene Hybrid Capture System HBV DNA assay for the quantitation of HBV in
      patient sera. STUDY DESIGN: Sensitivity and reproducibility were determined with
      10-fold dilution series of two Eurohep HBV reference plasma specimens.
      Furthermore, 196 sera from 14 children with chronic HBV infection and interferon
      therapy were tested with both assays. RESULTS: The detection limit was found to
      be 10(3) copies/ml with the Amplicor PCR assay compared to 10(6) to 10(7)
      copies/ml with the Digene hybridization assay. Both assays were quasi-linear over
      the measurable ranges. The new PCR assay proved to be very reliable. With the
      Amplicor PCR assay, 26.2% of the HBV DNA-positive clinical samples were found
      between 10(3) and 10(7) copies/ml and all of them tested below the detection
      limit with the hybridization assay. CONCLUSION: The Amplicor HBV Monitor Test
      shows excellent sensitivity and provides a valuable tool for the detection of HBV
      DNA in serum. It can be used for recognizing those patients who might benefit
      from antiviral therapy, for evaluation of the efficacy of anti-HBV therapy, and
      for validation of blood products.

PMID- 9562858
TI  - Routine diagnosis of herpes simplex virus (HSV) encephalitis by an internal DNA
      controlled HSV PCR and an IgG-capture assay for intrathecal synthesis of HSV
      antibodies.
AB  - BACKGROUND: The development of antiviral therapy increases the need for rapid,
      sensitive and reliable methods or combination of methods for diagnosis and
      monitoring herpes simplex encephalitis, HSE. OBJECTIVES: Evaluation of diagnostic
      performance of three successively developed HSV PCR assays when combined with a
      new capture ELISA for HSV intrathecal antibody production (ITT). STUDY DESIGN:
      During a 3.6 year period a total of 4.206 CSF and serum samples from about 4.140
      hospitalized patients with a tentative diagnosis of HSE were analyzed by a new
      ELISA for ITT. 1.962 CSF samples were examined also by PCR. Clinical signs and
      symptoms and additional tests were obtained on all ITT and/or PCR positive
      patients. In 1993 the PCR was a double PCR. In 1994 the PCR was a single PCR with
      internal inhibition control. Positive samples were confirmed by a different
      confirmative PCR to increase the specificity. From 1995 the PCR was as in 1994
      but samples were no longer divided in the serology routine laboratory. RESULTS: A
      total of 33 HSE cases was found (incidence 1.8 HSE per million people). All
      patients were treated with aciclovir. Three patients died, 9 patients had primary
      infection, 2 patients had HSE previously, and 2 patients relapsed. Only 11
      patients recovered satisfactory. Of all 37 positive ITT 7 were unlikely positive.
      False positive PCR was seen in 1993 and 1994, due to sample-to-sample
      contamination during division of samples, but was not seen since 1995 when this
      procedure was changed. The test results depended on the state of the disease.
      Thus, the sensitivity, specificity, PPV and NPV for ITT were highest when
      performed more than 1 week after debut of symptoms whereas these values were
      highest using PCR within the first week. CONCLUSION: Routine PCR diagnosis of HSE
      type 1 and 2 is a highly sensitive and specific method that should be performed
      together with serological ITT to cover the whole time span from debut of symptoms
      to several weeks after hospitalization.

PMID- 9562859
TI  - Comparative evaluation of three recombinant antigen-based enzyme immunoassays for
      detection of IgM and IgG antibodies to human parvovirus B19.
AB  - BACKGROUND: Diagnosis of acute and past infection with parvovirus B19 is based on
      detection of IgM and IgG antibodies. OBJECTIVES: To evaluate two commercial
      recombinant antigen-based enzyme immunoassay (EIA) test kits for detection of IgM
      and IgG antibodies to parvovirus B19 and to compare the commercial EIAs to in
      house EIA test procedures. STUDY DESIGN: A panel of 121 sera was used to compare
      the three IgM EIAs. The panel included 84 sera submitted for parvovirus B19
      testing and 37 sera that were IgM positive for other viral pathogens. The same
      serum panel plus an additional 14 sera submitted for B19 testing was used to
      compare the three IgG EIAs. The commercial EIAs were performed according to
      manufacturers' instructions. Using the in-house EIA test procedures as the
      reference, sensitivity and specificity for each of the commercial EIAs was
      determined. RESULTS: The commercial B19 IgM EIAs showed agreements of 95.0 and
      93.4% to the in-house IgM EIA. Compared to the in-house B19 IgM EIA, the
      commercial B19 IgM EIAs were 97.4 and 97.5% sensitive, respectively.
      Specificities were 93.5 and 91.4%, respectively. Sensitivities for the commercial
      IgG EIAs, compared to in-house IgG EIA, were 88.0 and 85.2%, respectively, and
      specificities were 94.1 and 98.0%. CONCLUSION: We found that the commercial
      parvovirus B19 IgM and IgG EIAs are comparable to standard in-house EIAs and are
      suitable for testing for B19 antibodies in human sera.

PMID- 9562860
TI  - A common immunological epitope existing between HIV-1 gp41 and human interferon
      alpha and -beta.
AB  - Based on the similar effects that HIV-1 gp41 like human type I interferons (IFN
      alpha and -beta) upregulated MHC expression and inhibited lymphocyte
      proliferation, we compared amino acid sequences of gp41 and human type I
      interferons (IFN-alpha and -beta), and found sequence-similarity existing between
      the immunosuppressive domain (aa583-599, LQARILAVERYLKDQQL) of HIV-1 gp41 and
      human IFN-alpha (region aa117-129) and IFN-beta (region aa128-134); besides, the
      immunosuppressive domain of HIV-1 gp41 shows sequence-homology with bovine and
      murine IFN-alpha and IFN-beta in the same region. We examined polyclonal
      antibodies to human IFN-alpha and IFN-beta respectively and found that both
      antibodies could recognize rsgp41 from two different sources. The polyclonal
      antibody to IFN-beta could bind to the immunosuppressive peptide (ISP, aa583-599,
      LQARILAVERYLKDQQL) of HIV-1 gp41, only when the ISP was coupled with carrier
      protein, and inhibit, if preincubated with rsgp41, binding of rsgp41 to human H9
      (T cells), Raji (B cells), and U937 (monocyte cells) completely. The polyclonal
      antibody to IFN-alpha could partially inhibit the binding of rsgp41 to U937 and
      Raji. These results indicate that a common immunological epitope exists between
      HIV-1 gp41 and human type I interferons.

PMID- 9562861
TI  - Activation and suppression of natural cellular immune functions by Pneumocystis
      carinii.
AB  - The regulatory role of soluble cytokines in innate cellular immune responses
      induced by Pneumocystis carinii was assessed in vitro in direct comparison to
      induction by Listeria monocytogenes. This report shows that P. carinii organisms,
      as well as L. monocytogenes, stimulated in whole spleen cell cultures of SCID
      mice the release of IFN-gamma, TNF-alpha/beta, IL-10, IL-12, and iNO. This
      response was independent of functional T cells. Both macrophages (M phi) and
      natural killer (NK) cells were necessary for either microorganism to induce
      release of these cytokines. Cocultures of purified M phi--including alveolar M
      phi--and purified NK cells indicated that no other cell population was
      necessarily involved. Microbial induction of NK cell-derived IFN-gamma has been
      reported to be mediated by the combined effects of TNF-alpha and IL-12 released
      by M phi upon adequate microbial stimulation. Interestingly, only L.
      monocytogenes, but not P. carinii organisms could directly induce detectable
      amounts of TNF-alpha/beta, IL-12, or iNO in purified M phi cultures. In dose
      response experiments, release of IFN-gamma, TNF-alpha/beta, and iNO was reduced
      at high relative concentrations of either microorganism. This high-dose
      suppression was at least partially controlled by M phi-produced IL-10. Our data
      show that, P. carinii potently induces activating and inhibitory innate cellular
      immune response mechanisms and indicate that the initial step of macrophage
      mediated NK cell activation might also involve other pathways than those
      described to date.

PMID- 9562862
TI  - Characterization of erythroid cell-derived natural suppressor activity.
AB  - Nucleated erythroid cells (NEC) have been previously reported to the capable of
      suppressing antibody-mediated primary (IgM) and secondary (IgG) immune responses
      to thymus-dependent antigens. In the present study we indicated that NEC,
      separated from the spleens of mice following phenylhydrazine treatment were able
      to suppress directly the proliferative response of preactivated B cells to
      lipopolysaccharide (LPS) in vitro. While being active in suppressing B cell
      blastogenesis, NEC, however, failed to reduce both cell proliferation and
      cytotoxic T lymphocyte (CTL) generation in an allogeneic mixed lymphocyte culture
      (MLC). NEC also lacked a significant effect on interleukin (IL)-2 production and
      utilization by concanavalin A (Con A)-activated T lymphocytes. The NEC-derived
      suppression of B cell proliferation was, at least in part, mediated by soluble
      molecules. The specific blockade of transforming growth factor (TGF)-beta
      synthesis with antisense oligodeoxynucleotides (OD) binding TGF-beta mRNA, as
      well as the neutralization of TGF-beta activity with anti-TGF-beta antibodies
      (Ab), resulted in a detectable diminished ability of the NEC-conditioned medium
      (CM) to suppress B cell blastogenesis. Taken together, the results suggest that:
      1) NEC may suppress directly B cell responses, while not affecting T cell ones;
      2) NEC may mediate their natural suppressor (NS) activity partially through
      releasing TGF-beta.

PMID- 9562863
TI  - A matrix metalloproteinase gene expressed in human T lymphocytes is identical
      with collagenase 3 from breast carcinomas.
AB  - The response of human T lymphocytes to various stimuli includes the expression of
      the matrix metalloproteinase (MMP) genes stromelysin 2, gelatinase A and
      gelatinase B. The proteins encoded by these genes could confer the capacity to
      degrade macromolecular components of the extracellular matrix (ECM), and to shed
      transmembrane proteins such as tumor necrosis factor (TNF), TNF receptor,
      Interleukin-6 receptor and Fas ligand. To identify further MMP genes transcribed
      in T lymphocytes exposed to phorbol 12-myristate 13-acetate and a calcium
      ionophore, we combined reverse transcription and polymerase chain reaction using
      primers specific for conserved domains and detected collagenase 3 transcripts,
      first described in a human breast cancer. However, when the sequence of the
      complementary DNA was compared, additional 23 nucleotides were found in the 5'
      nontranslated region of the lymphocyte messenger RNA (mRNA). Northern blot
      analysis revealed 2 major inducible mRNA species of 1.9 and 2.8 kilobases, whose
      levels were lower than those of stromelysin 2. The observation that activated T
      lymphocytes transcribe several MMP genes, including a collagenase, indicates that
      the effector functions of these cells include enzymatic activities towards most
      constituents of the ECM, as well as some transmembrane proteins relevant to
      inflammation and apoptosis.

PMID- 9562864
TI  - Inadequate anti-polysaccharide antibody responses in the chicken.
AB  - Chickens are notorious for the fact that they carry bacteria such as Salmonellae
      and Campylobacter, which can cause zoonoses by contamination of the end product,
      without hampering growth and development of the chicken itself. This carrier
      status can only been explained by the inability of the chickens immune system to
      eliminate the pathogen, this in turn being due to insufficient humoral responses
      towards the polysaccharides of the bacterial capsule. In a previous study, we
      demonstrated that in chickens a model thymus-independent type 2 (TI-2)
      polysaccharide antigen, trinitrophenylated Ficoll (TNP-Ficoll), hardly evokes a
      humoral immune response. Furthermore this TI-2 antigen was shown to exhibit a
      very specific initial localization pattern after intravenous injection, i.e. in
      the periellipsoidal lymphocyte sheaths (PELS) and the surrounding ring of
      macrophages. The functional equivalent of these macrophages in mammals, the
      marginal zone macrophages, were shown to suppress the humoral responses against
      TI-2 antigens. Therefore we investigated whether other standard TI-2 antigen
      models also induce low antibody responses, whether this low response is dose
      dependent, and whether macrophages are responsible for this low response. It was
      found that other TI-2 antigens, such as hydroxyethyl starch and detoxified
      lipopolysaccharides, also induced very low IgM and IgG responses, indicating a
      general phenomenon that could not be overcome by using a higher dose of antigen.
      In addition, selective depletion of splenic macrophages with liposomes containing
      dichloromethylene diphosphonate prior to immunization increased the specific
      humoral response to TD and TI-1 antigens, but failed to do so for TI-2 antigen.
      This result indicates that the low humoral responses are not (only) due to a
      macrophage suppressive activity but also to other yet unknown mechanisms, for
      example the lack of responsive B cells in the splenic PELS.

PMID- 9562865
TI  - Human IL-6 enhances human lymphocyte engraftment and activation but not human
      antibody production in SCIDhu PBL mice.
AB  - The SCIDhu PBL model of human Ig production was modified by using human
      interleukin-6 (hIL-6) secreting tumors for continuous hIL-6 production, in vivo.
      On day one, SCID mice were injected subcutaneously with 200 microliters PBS
      (control mice), 10(4) SP2/0-Ag14 cells (IL-6+ mice) or 10(4) hIL-6 secreting
      SP2/0-hIL6.17 cells (IL-6- mice). The mice were reconstituted with human PBMC on
      day two and immunized with 100 micrograms of tetanus toxoid (TT) on days two and
      fifteen. Serum hIL-6 concentrations in IL-6+ mice ranged between 2.9 and 38.1
      ng/ml by days 26-33. IL-6+ mice had enlarged spleens and lymph nodes (LN). Flow
      cytometry and histology showed that SCIDhu PBL mouse spleen, LN and peritoneal
      exudate cells (PEC) contained mostly murine myeloid lineage cells. In addition,
      many more human B cells, T cells and IL-2R(+)-activated lymphocytes were present
      in spleen, LN and PEC of IL-6+ mice. Despite enhanced lymphocyte engraftment and
      activation, by day 14 IL-6+ mice produced up to 6-fold less TT-specific IgG
      relative to total IgG than either control group. TT-specific and total Ig sera
      concentrations were equivalent in all three groups on days 26-33. Our results
      suggest that sustained circulating hIL-6 enhanced human delayed-type
      hypersensitivity (DTH)-like inflammatory responses with consequential inhibition
      of TT-specific IgG production in SCIDhu PBL mice.

PMID- 9562866
TI  - Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated
      peripheral blood mononuclear cells and is detected as an autoantigen in
      rheumatoid arthritis.
AB  - In order to characterize the autoimmune response participating in the
      pathogenesis of rheumatoid arthritis (RA) a cDNA expression library constructed
      from mRNAs which had been isolated from the inflamed synovium of an RA patients
      was screened with autologous IgG autoantibodies. This led to the identification
      of gene rasi-1 which encodes a protein showing sequence identity with the zinc
      binding matrix metalloproteinase MMP-19. MMP-19 is detected on the surface of
      activated PBMCs, TH1 lymphocytes, and Jurkat T lymphoma cells. It exhibits
      gelatinolytic activity and is recognized by autoantibodies in 26% and,
      respectively, 33% of sera collected from RA patients and systemic lupus
      erythematosus (SLE) patients. The novel autoantigen MMP-19 thus could play a role
      in the pathological processes participating in RA-associated joint tissue
      destruction.

PMID- 9562867
TI  - CD8 dimer usage on alpha beta and gama delta T lymphocytes from equine lymphoid
      tissues.
AB  - Eight murine monoclonal antibodies (mAb) were used to identify the equine CD8
      alpha or CD8 beta chains and to define the expression of these chains on
      lymphocytes from various lymphoid tissues. CD8 alpha was a 39 kDa protein and CD8
      beta was a 32 kDa protein. Both chains were expressed on most of the CD8+ T
      lymphocytes in the peripheral blood, spleen, thymus, mesenteric lymph nodes and
      ileal intraepithelial lymphocytes (IEL), however, in each lymphoid compartment a
      percentage of lymphocytes expressed only the CD8 alpha chain. The largest
      percentage of CD8 alpha alpha expressing T lymphocytes was 37.7% of the IELs.
      Purified T lymphocytes from the ileum expressing CD8 alpha beta co-expressed the
      alpha beta T cell receptor (TCR). In contrast, purified CD8+ T lymphocytes from
      the PBMC co-expressed either the alpha beta or gamma delta TCR by RT-PCR. Use of
      pooled anti-CD8 alpha mAb of the murine IgG2a isotype and rabbit complement
      resulted in lysis of the entire CD8 expressing population in peripheral blood
      mononuclear cells (PBMC). These results indicated that CD8 dimer usage by equine
      T lymphocytes is similar to other species and that the mAb described can be
      further used to separate equine CD8+ T lymphocyte subsets from the lymphoid
      tissues to define their function in protection against viral and other
      infections.

PMID- 9562868
TI  - There is no regulatory role for induced nitric oxide in the regulation of the in
      vitro proliferative response of bovine mononuclear cells to mitogens,
      alloantigens or superantigens.
AB  - Nitric oxide (NO) is a potent cellular mediator which has been shown to modulate
      several immune mechanisms. Between species, however, there are considerable
      differences regarding the signals required for induction of NO as well as the
      kind of cells capable of producing NO. The object of this study was to determine
      the kinetics of NO production of bovine blood mononuclear cells (boMNC)
      stimulated in vitro and to investigate whether it modulates their proliferative
      response following allogeneic (mixed leukocyte cultures, aMLC), mitogenic (PWM,
      Con A) or superantigenic (SEA, SEB) stimulation. NO production was indirectly
      determined with the Griess reagent measuring nitrite (NO2-). Significant but low
      amounts of NO could be detected as early as day 3 after in vitro stimulation and
      did noly slightly increase during the 6-8 day culture period. Superantigens (SEA,
      SEB) and aMLCs (4.3-5.2 microM NO2-) induced a significantly higher nitrite
      accumulation compared to Con A (2.6 microM NO2-). Generation of nitrite, most
      likely produced by monocytes/macrophages, could be inhibited by 1 mM N-monomethyl
      L-arginine (NMLA). Flow cytometric characterization of various cellular responses
      revealed no differences between cultures with or without NMLA. This included the
      determination of blastogenesis, absolute numbers of viable cells, expression
      density of activation markers (MHC class II, IL-2R alpha) and cellular
      subpopulations (CD4+, CD8+, sIg+) among blasts. In addition, exogenously provided
      NO via SNOG in non-toxic concentrations (10(-5)-10(-4) M) did not alter the
      proliferative reaction of boMNC in vitro. The results suggest that NO is induced
      after in vitro stimulation of boMNC, however, at a low level, and without having
      any positive or suppressive effects on the so far tested cellular parameters of
      activation and proliferation.

PMID- 9562869
TI  - Effects of administration of monoclonal antibodies (anti-CD4 or anti-CD8) on the
      development of autoimmune diseases in (NZW x BXSB)F1 mice.
AB  - (NZW x BXSB)F1 (W/BF1) mice spontaneously develop autoimmune diseases,
      characterized by lymphadenopathy, lupus nephritis, and immune thrombocytopenia
      associated with various autoantibodies such as anti-DNA, anti-platelet and anti
      cardiolipin antibodies (Abs). In the present study, we investigate the effects of
      administration of monoclonal Abs (anti-CD4 or anti-CD8 mAb) on the development of
      autoimmune diseases in W/BF1 mice. MAb was administered from the age of 7 weeks.
      Prolongation of survival rate and reduction of severity of autoimmune diseases
      were observed after treatment with anti-CD4 mAb. However, anti-CD8 mAb treatment
      accelerated the diseases. Serum levels of IFN-gamma and IL-10 in old W/BF1 mice
      were significantly high, whereas IL-4 levels were low in comparison with those of
      young W/BF1 mice; the expression of mRNA of IFN-gamma, IL-4 or IL-10 in CD4+ T
      cells of old W/BF1 mice was parallel to the serum levels of each cytokine. These
      observations suggest that CD4+ cells are involved in the development of
      autoimmune diseases in W/BF1 mice, and that CD8+ cells have a suppressive effect
      on the development of autoimmune diseases in W/BF1 mice.

PMID- 9562870
TI  - CD26 (dipeptidyl peptidase i.v.) on human T lymphocytes does not mediate adhesion
      of these cells to endothelial cells or fibroblasts.
AB  - We have examined the role of CD26 (dipeptidyl peptidase IV) in the adhesion of
      resting and activated T lymphocytes to endothelial cells and fibroblasts. For
      this purpose, we ran a short-time adhesion assay under different strategies:
      Adhesion of T lymphocytes was determined in the presence of different anti-CD26
      monoclonal antibodies, or in the presence of synthetic inhibitors of the
      enzymatic function of CD26. In addition, the expression of CD26 on T lymphocytes,
      which were adherent to endothelial cells or fibroblasts, was performed by flow
      cytometric analysis. We found that the anti-CD26 monoclonal antibodies tested
      here were not able to inhibit T cell adhesion to monolayers of endothelial cells
      or fibroblasts. Secondly, synthetic inhibitors of the enzymatic function of CD26
      had no effect on the adhesion of T lymphocytes to endothelial cells or
      fibroblasts. Furthermore, CD26-positive T cells were not accumulated in the
      adherent population. These results suggest that CD26 on T lymphocytes plays no
      role in T cell adhesion to endothelial cells or fibroblasts.

PMID- 9562871
TI  - Relative contributions of decay accelerating factor (DAF), membrane cofactor
      protein (MCP) and CD59 in the protection of melanocytes from homologous
      complement.
AB  - Complement regulatory molecules, membrane cofactor protein (MCP), decay
      accelerating factor (DAF) and CD59, protect body cells from autologous
      complement. They have wide tissue distribution but nothing is known about the
      expression of these molecules on human melanocytes. Since melanocytes are lysed
      in the lesional skin of patients with a depigmentary disorder vitiligo, it is
      important to compare the protection offered by complement regulatory molecules to
      melanocytes present in normal and vitiligo epidermis, against autologous
      complement. From this point of view, we investigated the differential expression
      of MCP, DAF and CD59 on normal cultured human melanocytes and assessed their
      individual contribution in the protection of these cells against complement
      mediated damage. Flow cytometric analysis showed that MCP and DAF but not CD59
      were expressed on cultured melanocytes. When heat inactivated sera of patients
      with vitiligo were used as a source of anti-melanocyte antibody to sensitize
      melanocytes, and guinea pig serum (GpS) or normal human serum (NHS) as a source
      of complement, GpS was found to be more effective in causing the lysis of
      melanocytes than NHS. When melanocytes were sensitized with autoantibody as well
      as F(ab')2 fragment of either anti-MCP or anti-DAF and subsequently incubated
      with NHS or GpS, both antibody fragments increased the killing of melanocytes by
      NHS as well as by GpS. F(ab')2 fragment of anti-DAF was much more effective in
      causing enhancement of lysis than that of anti-MCP. Thus, cultured normal human
      melanocytes express functionally active MCP and DAF but not CD59. Contribution of
      DAF in protecting melanocytes against complement attack was much more than that
      of MCP.

PMID- 9562872
TI  - Lack of protection from HIV infection by the mutant HIV coreceptor CCR5 in
      intravenously HIV infected hemophilia patients.
AB  - The CCR5 chemokine receptor is an important coreceptor for macrophage-tropic HIV
      strains. Homozygous carriers of the mutated CCR5 receptor with a 32 bp deletion
      (delta 32-CCR5) are highly protected against HIV infection. A protective effect
      has also been described for heterozygous individuals carrying both mutated and
      wildtype CCR5 receptors. We compared the frequency of the mutated delta 32-CCR5
      HIV coreceptor in HIV positive patients infected by sexual contact (N = 160) with
      intravenously HIV infected hemophilic patients (N = 84) and HIV negative
      individuals (N = 421). We found no protective effect of delta 32-CCR5 HIV
      coreceptor in hemophilic patients (p = 0.0134). If proteins of plasma
      concentrates would be responsible for facilitating the entry of HIV macrophages
      by upregulation of the CCR5 wildtype receptor it would be of therapeutical
      interest to identify the responsible plasma proteins.

PMID- 9562873
TI  - Histamine and tyramine degradation by food fermenting microorganisms.
AB  - Microorganisms suitable for food fermentation were examined with regard to their
      potential to degrade histamine and tyramine. Out of 64 lactic acid bacteria
      evaluated in this study, 27 degraded histamine and one tyramine, respectively,
      with low activity. Among 32 strains of Brevibacterium linens and coryneform
      bacteria, 21 exhibited histamine and tyramine oxidase activity. None of 20
      strains of Staphylococcus carnosus tested degraded histamine or tyramine. One
      strain out of nine strains of Geotrichum candidum degraded tyramine slightly.
      Among 44 strains of Micrococcus sp. examined, 17 degraded either one or two
      biogenic amines. In this study Micrococcus varians (M. varians) LTH 1540
      exhibited the highest tyramine oxidase activity of all strains tested and was
      therefore investigated in detail. The enzyme was found to be located in the
      cytoplasm and was not membrane bound. The reaction end product p-hydroxyphenyl
      acetic acid was detected by HPLC analysis. An activity staining for the amine
      oxidase in a native polyacrylamide gel based on the formation of H2O2 during
      amine oxidation was developed. Resting cells of the strain exhibited optimal
      tyramine oxidase activity at a pH of 7 at 37-40 degrees C. The enzyme in the cell
      free extract had a pH optimum between 7-8. The enzyme activity was decreased by
      NaCl, glucose and hydralazine. Phenylethylamine and tryptamine were oxidized at
      lower concentrations than tyramine. The potential for amine degradation was not
      found to be associated with that of formation of biogenic amines, as 23
      microorganisms with the ability to metabolise biogenic amines exhibited no
      decarboxylase activity toward histidine, tyrosine, phenylalanine, lysine or
      ornithine.

PMID- 9562874
TI  - Enterobacteriaceae found in high numbers in fish, minced meat and pasteurised
      milk or cream and the presence of toxin encoding genes.
AB  - Enterobacteriaceae were found in high numbers after storage at 7 degrees C in 6%
      of consumers packs of pasteurised milk or cream, in 31% of retailed fish and in
      100% of retail packs of minced meat. Seventy two fresh-water fishes, 40 packs of
      minced meat and 430 milk packs were sampled. One hundred and eighty four isolates
      were randomly picked from Tryptone glucose extract (TGE) agar (30 degrees C for
      3d) or Violet red bile glucose (VRBG) agar (37 degrees C for 1d). In minced meat,
      Serratia liquefaciens, Hafnia alvei, Rahnella aquatilis were frequently
      encountered. On fish, the most frequently found species were R. aquatilis, and in
      milk, the dominating species were S. liquefaciens, H. alvei and R. aquatilis. One
      to three isolates of Citrobacter freundii were found in all three food
      categories. Using a polymerase chain reaction (PCR) technique, the gene of
      Escherichia coli heat-labile toxin (lt) was indicated in one fish isolate of R.
      aquatilis whereas heat-stable toxin genes (s.t.) were indicated in four H. alvei
      isolates, two originating from fish and two from minced meat. Positive PCR
      reaction for vero cytotoxin genes were found in one H. alvei strain originating
      from fish (vt1), in two S. liquefaciens strains from minced meat (vt2), and in a
      C. freundii reference strain. One of the st-positive H. alvei strains from meat
      harboured the eaeA gene involved in the attaching phenotype of enteropathogenic
      E. coli.

PMID- 9562875
TI  - Identification, assessment and management of food-related microbiological
      hazards: historical, fundamental and psycho-social essentials.
AB  - Microbiological risk assessment aimed at devising measures of hazard management,
      should take into account all perceived hazards, including those not empirically
      identified. It should also recognise that safety cannot be "inspected into" a
      food. Rather hazard management should be the product of intervention strategies
      in accordance with the approach made mandatory in the EU Directive 93/43 and the
      USDA FSIS Pathogen Reduction HACCP system; Final Rule. It is essential too that
      the inherent variability of the biological attributes affecting food safety is
      recognised in any risk assessment. The above strategic principles may be
      conceptualised as a four-step sequence, involving (i) identification and
      quantification of hazards; (ii) design and codification of longitudinally
      integrated ("holistic") technological processes and procedures to eliminate, or
      control growth and metabolism of, pathogenic and toxinogenic organisms; (iii)
      elaboration of microbiological analytical standard operating procedures,
      permitting validation of "due diligence" or responsible care, i.e. adherence to
      adopted intervention strategies. This should be supported by empirically assessed
      reference ranges, particularly for marker organisms, while the term "zero
      tolerance" is refined throughout to tolerable safety limit; (iv) when called for,
      the need to address concerns arising from lay perceptions of risk which may lack
      scientific foundation. In relation to infectious and toxic hazards in the
      practical context the following general models for quantitative holistic risk
      assessment are presented: (i) the first order, basic lethality model; (ii) a
      second approximation taking into account the amount of food ingested in a given
      period of time; (iii) a further adjustment accounting for changes in colonization
      levels during storage and distribution of food commodities and the effects of
      these on proliferation of pathogens and toxin production by bacteria and moulds.
      Guidelines are provided to address: (i) unsubstantiated consumer concern over the
      wholesomeness of foods processed by an innovative procedure; and (ii) reluctance
      of small food businesses to adopt novel strategies in food safety. Progress here
      calls for close cooperation with behavioural scientists to ensure that investment
      in developing measures to contain risk deliver real benefit.

PMID- 9562876
TI  - Growth of Pseudomonas fluorescens and Pseudomonas fragi in a meat medium as
      affected by pH (5.8-7.0), water activity (0.97-1.00) and temperature (7-25
      degrees C).
AB  - A total of 59 strains of Pseudomonas, isolated from meat products, were grown in
      micro-titer plates in a meat medium over a range of pH (5.8-7.0), alpha w (0.97
      1.00) and temperature (7-25 degrees C). Growths were performed in a meat broth
      with an automated turbidimeter (Bioscreen C, Labsystem, France). The growth
      curves obtained in this study did not have sigmoidal shapes making it impossible
      to calculate growth parameters using the Gompertz equation. The medium was weakly
      oxygenated in the micro-titer plates and reached 0%-dissolved oxygen at the
      beginning of the exponential phase. Strains were separated into two groups: P.
      fragi and P. fluorescens. Strains of P. fragi had shorter lag times than those of
      P. fluorescens. The impact of such results is interesting in that these could
      assist to explain the succession of flora that is observed during the processing
      of meat: P. fluorescens is the dominant bacteria among Pseudomonas spp. at the
      beginning of a slaughter line and P. fragi becomes dominant during the chilling
      process.

PMID- 9562877
TI  - Efficacy of heat and ethanol spore treatments for the isolation of psychrotrophic
      Clostridium spp. associated with the spoilage of chilled vacuum-packed meats.
AB  - Psychrotrophic Clostridium spp. associated with chilled meat spoilage are
      difficult to isolate and culture. In this study the kinetics of heat and ethanol
      spore inactivation was determined as a first step towards optimising the recovery
      of psychrotrophic clostridial spores from meat and environmental samples. To
      determine heat inactivation, spores of nine isolates associated with spoiled
      chilled or frozen meat and a psychrotrophic reference strain Clostridium
      algidicarnis NCFB 2931, suspended in phosphate buffer, were exposed to
      temperatures between 75 degrees C and 95 degrees C for 0 to 120 min using a
      submerged tube procedure. Survivors after various temperature-time combinations
      were enumerated on Peptone Yeast Extract Glucose Starch (PYGS) agar containing
      lysozyme. D-values and z-values for each spore suspension were determined from
      their respective survival curves. To determine ethanol inactivation, similar
      phosphate buffer spore suspensions were mixed with equal volumes of absolute
      ethanol, incubated at 20 degrees C and survivors enumerated on lysozyme
      containing PYGS agar after 0 to 300 min. Based on spore heat inactivation, the 10
      isolates could be grouped as having either heat-sensitive or heat-resistant
      spores. For heat-sensitive spore types, 60 min ethanol treatment gave maximum
      spore recovery whereas for heat-resistant spore types, heat treatment at 80
      degrees C for 10 min gave the best recovery. When the spore heat-resistance type
      is unknown, as would be the case when attempting an isolation from spoiled
      product, both an ethanol treatment and a separate heat treatment should be used,
      to ensure maximum spore recovery.

PMID- 9562878
TI  - Influence of culture media on the recovery of psychrotrophic Clostridium spp.
      associated with the spoilage of vacuum-packed chilled meats.
AB  - This study was undertaken to determine the influence of culture media on the
      quantitative recovery of vegetative cells and spores of psychrotrophic
      Clostridium spp. associated with the spoilage of chilled meats. For recovery of
      vegetative cells and spores (presumptive counts), 24 h or 48 h broth cultures in
      Peptone Yeast Extract Glucose Starch (PYGS) broth were used; for spore counts,
      concentrated spore suspensions derived from 35-day cultures were used. For
      presumptive counts, seven non-selective and eight selective media were tested.
      Recovery of psychrotrophic clostridia with optimum growth temperatures between 15
      degrees C and 20 degrees C was best with non-selective media, such as Peptone
      Yeast Extract Glucose Starch (PYGS) agar with lysozyme; recovery of clostridia
      with growth optima between 25 degrees C and 30 degrees C was best with selective
      media, such as Shahidi Ferguson Perfringens (SFP) agar. For organisms with the
      lower optimum growth temperature (heat-sensitive group) spore recovery after heat
      treatment (80 degrees C for 10 min) was best if a 2 M (pH 10) thioglycollate
      treatment (10 min at 45 degrees C) was used, followed by plating onto a lysozyme-
      or egg-yolk-containing medium. For organisms with the higher optimum growth
      temperature (heat-resistant group), spore recovery was best on Glucose Starch
      agar without added lysozyme. The diversity among psychrotrophic Clostridium spp.
      associated with chilled meat spoilage precludes the identification of a single
      'best' recovery medium or technique. Consequently, a variety of complementary
      selective techniques and media must be used if comprehensive recovery is to be
      assured.

PMID- 9562879
TI  - Pediocin N5p from Pediococcus pentosaceus: adsorption on bacterial strains.
AB  - Pediocin N5p is a bacteriocin produced by Pediococcus pentosaceus isolated from
      wine. It is absorbed on both sensitive and resistant Gram-positive and Gram
      negative bacteria in non specific (non lethal) sites and higher values, up to 30%
      are observed in sensitive strains suggesting the presence of particular (lethal)
      receptors. Cell death without lysis is produced by the action of pediocin on
      sensitive strains. The cations Mg2+ and Mn2+ increase the pediocin binding by 80
      and 100%, respectively. Treatment of sensitive cells with proteolytic enzymes and
      1% SDS increases the subsequent binding of bacteriocin by 100 and 25%,
      respectively. As a lipid moiety of pediocin N5p is critical to its activity,
      probably a hydrophobic interaction with the peptidic receptor, stabilized by Mn2+
      or Mg2+ might be established. Pediocin N5p adsorption is not affected by ethanol
      and SO2, two factors involved in vinification.

PMID- 9562880
TI  - Production of staphylococcal enterotoxin H under controlled pH and aeration.
AB  - The effects of controlled pH and aeration on the growth of Staphylococcus aureus
      strain FRI-569 and production of enterotoxin H (SEH) were studied. S. aureus FRI
      569 did not grow well anaerobically. Aeration permitted better growth of cells
      especially at a flow rate of 300 cc/min. The optimal pH for S. aureus FRI-569
      growth was 7.0, with less growth being observed at pH 6.5 and 7.5 or with no pH
      control. Very little SEH (< 21 ng/ml) was produced by S. aureus strain FRI-569
      under anaerobic incubation. High SEH production was observed with aeration at 300
      cc/min. Increasing aeration to 400 cc/min or decreasing it to 200 cc/min resulted
      in reduced SEH production. Larger amounts of SEH were produced when the pH was
      controlled at 7.0, while maintaining the pH at 6.5 or 7.5 resulted in lower
      levels of SEH being produced. However, the amounts were still greater than those
      observed when the pH was not controlled.

PMID- 9562881
TI  - The adhesion of Bacillus cereus spores to epithelial cells might be an additional
      virulence mechanism.
AB  - Four out of ten Bacillus cereus strains produced spores able to adhere to
      monolayers of Caco-2 cells (human epithelial cells). One of these strains has
      been involved in an outbreak of food poisoning where the symptoms were more
      severe and persisted for longer than a normal B. cereus food poisoning. The
      hydrophobicity of the spores is a contributing factor for the adhesion to occur.
      The spores are able to germinate in an environment similar to that of the small
      intestine and then the vegetative cells can produce the enterotoxin directly at
      the target place. A concentrated and active form of the enterotoxin will be taken
      up by the epithelial cells in the small intestine. Spore adhesion could be an
      important virulence factor for some B. cereus strains.

PMID- 9562882
TI  - Mathematical modelling of microbial growth in packaged refrigerated beef stored
      at different temperatures.
AB  - Gompertz and logistic models were fitted to experimental counts of microorganisms
      growing in beef stored at 0, 4, 7, 9 and 10 degrees C. Samples were packaged in
      polyethylene (high gaseous permeability) and in EVA/SARAN/EVA (low gaseous
      permeability) films, being EVA ethyl vinyl acetate and SARAN polyvinyl and
      polyvinylidene chloride copolymer. Lag phase duration (LPD) and specific growth
      rate (mu) were obtained as derived parameters for lactic acid bacteria,
      Enterobacteriaceae, Pseudomonas sp. and psychrotrophic microorganisms. The
      reciprocal of LPD was fitted to an Arrhenius type equation; LPD of lactic acid
      bacteria showed a marked dependence on temperature, with activation energy values
      (ELPD) of 222.2 and 216.9 kJ/mol for polyethylene and ESE respectively. The
      effect of initial microbial population at different storage temperatures on
      adaptation period was analyzed. As the initial microbial population increased,
      adaptation period decreased for all studied microorganisms and for both packaging
      films. The effect of temperature on specific growth rate was better interpreted
      by the Arrhenius model than by the linear or the square root equations.
      Psychrotrophic microorganisms in beef showed the highest activation energy values
      for specific growth rate (E mu) in both packaging films, being E mu 85.50 and
      103.10 KJ/mol for polyethylene and ESE film respectively. In both films,
      Enterobacteriaceae showed the lowest E mu values, being 15.33 and 59.89 kJ/mol in
      ESE and polyethylene respectively. The final number of microorganisms (maximum
      population density) did not show significant changes with storage temperature.

PMID- 9562883
TI  - Study of the microbial ecology of cold-smoked salmon during storage at 8 degrees
      C.
AB  - Microbiological, chemical and sensory changes in cold-smoked salmon were studied
      during 5 weeks of vacuum storage at 8 degrees C. The aerobic 20 degrees C viable
      count reached its maximum level after 6 days (3 x 10(6) cfu g-1) however, the
      shelf-life of the product was estimated to be 2 or 3 weeks by the panellists,
      confirming that there is no correlation between those two factors. Acid, pungent,
      sour and rancid odours and flavours and pasty texture were the main spoilage
      characteristics. Trimethylamine did not play a major role in the spoilage
      mechanisms as only small amounts were produced. Two-hundred and seventy strains
      were collected over the storage period, purified and characterized. During the
      first 2 weeks, Gram-negative bacteria were dominant, mainly represented by S.
      putrefaciens immediately after the smoking process and then P. phosphoreum.
      Aeromonas spp. were present throughout the storage but in smaller amounts. Gram
      negative bacteria then progressively decreased while Gram-positive bacteria,
      dominated by lactic acid bacteria (LAB), became by far the most common variety
      found. Carnobacterium piscicola was widely represented (97/155 LAB isolates). A
      diversification was observed at the end of the storage, with the appearance of L.
      farciminis, L. sake and L. alimentarius. Occurrence of yeasts and moulds was
      quite rare. Spoilage potential of the strains was tested on a sterile smoked
      salmon extract juice. Shewanella putrefaciens, Aeromonas spp. and Brachothrix
      spp. produced strong off-odours while most of the LAB and P. phosphoreum seemed
      not to be involved in spoilage.

PMID- 9562884
TI  - Comparative study of lactic acid bacteria house flora isolated in different
      varieties of 'chorizo'.
AB  - A total of 516 strains of lactic acid bacteria isolated from 'chorizo' (a Spanish
      dry fermented sausage) were identified. The 'chorizo' was from three zones of
      Castilla and Leon in Spain: Burgos, Segovia and Salamanca. Two factories were
      chosen in each zone and the samples were taken at three stages of ripening. L.
      sake was the most predominant species present (68.8%) followed by L. curvatus
      (16.47%) and Pediococcus sp. (8.52%). Different strains that do not belong to the
      above species were grouped as Lactobacillus sp. Group S1 comprising maltose and
      lactose negative L. sake was the main group present in all factories except in a
      factory in Segovia where group S3 comprising lactose positive L. sake and
      pediococci were the predominant ones. Group S1 increased during the ripening
      process in all six factories and it dominated in the ripened 'chorizo' except in
      the mentioned factory in Segovia. In general strains of L. sake and L. curvatus
      which fermented maltose but not lactose were more dominant at the beginning and
      in the middle of the process, whereas, L. sake and L. curvatus which could
      ferment lactose, or lactose and maltose occurred in higher numbers in semi
      ripened 'chorizo' and in the final product. This indicates that strains which
      could ferment lactose were more competitive towards the end of the process.
      Strains from group S1 were the microorganisms responsible for the pH drop in most
      of the factories, giving the correct texture. As a result it would appear that a
      strain from this group would be most suitable for use as starter culture.

PMID- 9562885
TI  - Survival of heat-shocked Yersinia enterocolitica after irradiation in ground
      pork.
AB  - Earlier studies conducted in our laboratory showed that heat-shocked Yersinia
      enterocolitica (45 degrees C for 60 min) are more resistant to a subsequent beat
      treatment of 55 or 60 degrees C in ground pork than cells not previously heat
      shocked. The increased thermotolerance was partly attributed to the production of
      stress proteins. The present study was performed to determine if the stress
      proteins produced by heating could also afford protection to the cells to
      irradiation. As part of the study, the effect of air versus vacuum packaging on
      survival of Yersinia to irradiation was also examined. Irradiating the inoculated
      pork at 1.0 kGy was sufficient to completely eliminate this pathogen. The
      irradiation D value for both heat-shocked and non-heat-shocked cells was
      statistically the same (0.15 kGy). Neither heat-shocking Yersinia nor packaging
      under vacuum resulted in increased resistance of this organism to irradiation. In
      addition, no effect was seen in virulence of the cells after these treatments,
      when compared with controls.

PMID- 9562886
TI  - Occurrence of fumonisins in Spanish beers analyzed by an enzyme-linked
      immunosorbent assay method.
AB  - This study describes the occurrence of fumonisin in a survey of 32 Spanish beers,
      including some non-alcoholic beers. The analysis was conducted using an enzyme
      linked immunosorbent assay (ELISA) method and, in the range assayed (0-100 ng
      fumonisin B1/ml spiked-beer), recovery rates were about 81%, with variation
      coefficients that did not exceed 4.2%. The detection limit with this method was 3
      ng fumonisins/ml beer. Results for the fourteen positive samples (43.8% of total
      samples) showed that the lowest amount of fumonisins found in a positive sample
      was 4.76 ng/ml and the highest was 85.53 ng/ml.

PMID- 9562887
TI  - Molecular evolution of viruses--Past and Present, Part 2--An introduction.
AB  - The evolution of viruses is reviewed within the perspective of the concepts on
      the evolution of the lipid membrane bound vesicular structures in the prebiotic
      soup through the ideas on evolution of cells during the RNA World and the
      transition into the DNA World. The ancient Archeae bacteria and their retrons
      that carry the bacterial reverse transcriptase gene and their unique protein
      splicing capability provide an indication of the evolutionary path for
      retroviruses and, independently, for RNA and DNA viruses of the prokaryotic
      Archeae bacteria and the eukaryotic yeast and fungi.

PMID- 9562888
TI  - Origin and evolution of viruses.

PMID- 9562889
TI  - Evolution of a common structural core in the internal ribosome entry sites of
      picornavirus.
AB  - The translational control involving internal ribosome binding occurs in
      poliovirus (PV), human rhinoviruses (HRV), encephalomyocarditis virus (EMCV),
      foot-and-mouth disease virus (FMDV), and hepatitis A virus (HAV). Internal
      ribosome binding utilizes cis-acting genetic elements of approximately 450
      nucleotides (nt) termed the internal ribosome entry sites (IRES) found in these
      picornaviral 5'-untranslated region (5'UTR). Although these IRES elements are
      quite different in their primary sequence, a similar folding structure with a
      conserved 3' structural core exists in the IRES. Phylogenetic analysis and RNA
      folding of the 5' UTR of picornaviruses, including PV types 1-3, coxsackievirus
      types A and B, swine vesicular disease virus, echoviruses, enteroviruses (human
      and bovine), HRV, HAV, EMCV, mengovirus, Theiler's murine encephalomyelitis
      viruses, FMDV, and equine rhinoviruses, indicates that the predicted conserved
      structural core is indeed a general structural feature for all members of the
      picornavirus family. The evolution of a common structural core likely occurred by
      the gradual addition or deletion of structural domains and elements to preserve a
      similar tertiary structure that facilitates the utilization of the IRES in
      specific host-cell environments.

PMID- 9562890
TI  - Evolution of viral DNA-dependent DNA polymerases.
AB  - DNA viruses as their host cells require a DNA-dependent DNA polymerase (Pol) to
      faithfully replicate their genomic information. Large eukaryotic DNA viruses as
      well as bacterial viruses encode a specific Pol equipped with a proofreading 3'
      5'-exonuclease, and other replication proteins. All known viral Pol belong to
      family A and family B Pol. Common to all viral Pol is the conservation of the 3'
      5'-exonuclease domain manifested by the three sequence motifs Exo I, Exo II, and
      Exo III. The polymerase domain of family A and B Pol is clearly distinguishable.
      Family A Pol share 9 distinct consensus sequences, only two of them are
      convincingly homologous to sequence motif B of family B Pol. The putative
      sequence motifs A, B, and C of the polymerase domain are located near the C
      terminus in family A Pol and more central in family B Pol. Thus, family A Pol
      show a significant greater spacing between the Exo III motif and the Pol motif A
      that is especially extended in the case of the mitochondrial Pol gamma. From each
      host and virus family whenever possible the consensus sequences of two distantly
      related polymerase species were aligned for assessment of phylogenetic trees,
      using both maximum parsimony and distance methods, and evaluated by bootstrap
      analysis. Three alternative methods yielded trees with identical major groupings.
      A subdivision of viral family B Pol was achieved resulting in a branch with Pol
      carrying out a protein-primed mechanism of DNA replication, including
      adenoviruses, bacteriophages and linear plasmids of plant and fungal origin.
      Archaebacterial Pol and cellular Pol epsilon were consistently found at the base
      of this branch. Another major branch comprised alpha- and delta-like viral Pol
      from mammalian herpesviruses, fish lymphocystis disease virus, insect ascovirus,
      and chlorella virus. Due to a lower branch integrity Pol of T-even
      bacteriophages, poxviruses, African swine fever virus, fish herpesvirus, and
      baculoviruses were not clearly resolved and placed in alternate groupings. A
      composite and rooted tree of family A and B Pol shows that viral Pol with a
      protein-priming requirement represent the oldest viral Pol species suggesting
      that the protein-primed mechanism is one of the earliest modes of viral DNA
      replication.

PMID- 9562891
TI  - Is the major capsid protein of iridoviruses a suitable target for the study of
      viral evolution?
AB  - Iridoviruses are large cytoplasmic DNA viruses that are specific for different
      insect or vertebrate hosts. The major structural component of the non-enveloped
      icosahedral virus particles is the major capsid protein (MCP) which appears to be
      highly conserved among members of the family Iridoviridae, Phycodnaviridae, and
      African swine fever virus. The amino acid sequences of the known MCPs were used
      in comparative analyses to elucidate the phylogenic relationships between
      different cytoplasmic DNA viruses including three insect iridoviruses (Tipula
      iridescent virus, Simulium iridescent virus, Chilo iridescent virus), seven
      vertebrate iridoviruses isolated either from fish (lymphocystis disease virus,
      rainbow trout virus, European catfish virus, doctor fish virus), amphibians (frog
      virus 3), or reptiles (turtle virus 3, turtle virus 5), one member of the family
      Phycodnaviridae (Paramecium bursaria Chlorella virus type 1), and African swine
      fever virus. These analyses revealed that the amino acid sequence of the MCP is a
      suitable target for the study of viral evolution since it contains highly
      conserved domains, but is sufficiently diverse to distinguish closely related
      iridovirus isolates. Furthermore the results suggest that a substantial revision
      of the taxonomy of iridoviruses based on molecular phylogeny is required.

PMID- 9562893
TI  - Genomic organization and evolution of the human herpesviruses.
AB  - Members of the Herpesviridae family have been isolated from most animal species
      examined. Of approximately 100 individual virus species, eight have been isolated
      from humans, and three of these only within the last 10 years. Fortunately, there
      is now an enormous amount of sequence data from many of these viruses,
      particularly the eight human herpesviruses. This wealth of sequence information
      from such a diverse group of related viruses provides a unique resource for
      studies of viral gene evolution, comparative gene function, and virus
      identification.

PMID- 9562894
TI  - Molecular ecology and evolution of Streptococcus thermophilus bacteriophages--a
      review.
AB  - Bacteriophages attacking Streptococcus thermophilus, a lactic acid bacterium used
      in milk fermentation, are a threat to the dairy industry. These small isometric
      headed phages possess double-stranded DNA genomes of 31 to 45 kb. Yoghurt-derived
      phages exhibit a limited degree of variability, as defined by restriction pattern
      and host range, while a large diversity of phage types have been isolated from
      cheese factories. Despite this diversity all S. thermophilus phages, virulent and
      temperate, belong to a single DNA homology group. Several mechanisms appear to
      create genetic variability in this phage group. Site-specific deletions, one type
      possibly mediated by a viral recombinase/integrase, which transformed a temperate
      into a virulent phage, were observed. Recombination as a result of superinfection
      of a lysogenic host has been reported. Comparative DNA sequencing identified up
      to 10% sequence diversity due to point mutations. Genome sequencing of the
      prototype temperate phage phi Sfi21 revealed many predicted proteins which showed
      homology with phages from Lactococcus lactis suggesting horizontal gene transfer.
      Homology with phages from evolutionary unrelated bacteria like E. coli (e.g.
      lambdoid phage 434 and P1) and Mycobacterium phi L5 was also found. Due to their
      industrial importance, the existence of large phage collections, and the whole
      phage genome sequencing projects which are currently underway, the S.
      thermophilus phages may present an interesting experimental system to study
      bacteriophage evolution.

PMID- 9562895
TI  - Viruses infecting marine brown algae.
AB  - Viruses infecting algal hosts possess large double-stranded DNA as genomes. We
      have recently identified a family of viruses specific for filamentous brown
      algae. In contrast to the better known Chlorella viruses with their lytic
      infection cycle, marine brown algal viruses latently occur in their host cells
      and are induced to multiply in response to a variety of external stimuli such as
      change in light and temperature. Here, I summarize the known properties of this
      family of viruses and discuss their taxonomic classification.

PMID- 9562897
TI  - Long-term psychological evaluation of intersex children.
AB  - Treatment of psychological problems of 59 children with a physical intersex
      condition is described. The group consisted of 18 female pseudohermaphrodites
      with congenital adrenal hyperplasia (CAH), 20 male pseudohermaphrodites and 2
      true hermaphrodites born with ambiguous external genitalia assigned the female
      sex (ambiguous girls), 14 male pseudohermaphrodites born with completely female
      external genitalia and assigned the female sex (completely female group), and 5
      male pseudohermaphrodites born with ambiguous external genitalia and assigned the
      male sex. Despite the sex assignment, genital organ correction soon after birth,
      psychological counseling of parents and intensive psychotherapy of the children,
      general psychopathology developed equally in all 4 groups (39% of total group).
      Although 87% of the girls with a physical intersex condition developed in line
      with the assigned sex, 13% developed a gender identity disorder though only 1
      girl (2%) failed to accept the assigned sex. Gender identity disorder and deviant
      gender role were in evidence only in girls with CAH and girls of the ambiguous
      group. Biological and social factors seem responsible for the development of
      gender identity disorder, such as pre- and postnatal hormonal influences on the
      brain enabling deviant gender role behavior to develop, and an inability on the
      part of parents to accept the sex assignment. A reconsideration of the sex
      assignment in male pseudohermaphrodites and true hermaphrodites born with
      ambiguous external genitalia is discussed.

PMID- 9562892
TI  - The origin and evolution of human T-cell lymphotropic virus types I and II.
AB  - Studies on human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) are
      briefly reviewed from the viewpoint of molecular evolution, with special
      reference to the evolutionary rate and evolutionary relationships among these
      viruses. In particular, it appears that, in contrast to the low level of
      variability of HTLV-I among different isolates, individual isolates form
      quasispecies structures. Elucidating the mechanisms connecting these two
      phenomena will be one of the future problems in the study of the molecular
      evolution of HTLV-I and HTLV-II.

PMID- 9562896
TI  - Origin, adaptation and evolutionary pathways of fungal viruses.
AB  - Fungal viruses or mycoviruses are widespread in fungi and are believed to be of
      ancient origin. They have evolved in concert with their hosts and are usually
      associated with symptomless infections. Mycoviruses are transmitted
      intracellularly during cell division, sporogenesis and cell fusion, and they lack
      an extracellular phase to their life cycles. Their natural host ranges are
      limited to individuals within the same or closely related vegetative
      compatibility groups. Typically, fungal viruses are isometric particles 25-50 nm
      in diameter, and possess dsRNA genomes. The best characterized of these belong to
      the family Totiviridae whose members have simple undivided dsRNA genomes
      comprised of a coat protein (CP) gene and an RNA dependent RNA polymerase (RDRP)
      gene. A recently characterized totivirus infecting a filamentous fungus was found
      to be more closely related to protozoan totiviruses than to yeast totiviruses
      suggesting these viruses existed prior to the divergence of fungi and protozoa.
      Although the dsRNA viruses at large are polyphyletic, based on RDRP sequence
      comparisons, the totiviruses are monophyletic. The theory of a cellular self
      replicating mRNA as the origin of totiviruses is attractive because of their
      apparent ancient origin, the close relationships among their RDRPs, genome
      simplicity and the ability to use host proteins efficiently. Mycoviruses with
      bipartite genomes (partitiviruses), like the totiviruses, have simple genomes,
      but the CP and RDRP genes are on separate dsRNA segments. Because of RDRP
      sequence similarity, the partitiviruses are probably derived from a totivirus
      ancestor. The mycoviruses with unencapsidated dsRNA-like genomes (hypoviruses)
      and those with bacilliform (+) strand RNA genomes (barnaviruses) have more
      complex genomes and appear to have common ancestry with plant (+) strand RNA
      viruses in supergroup 1 with potyvirus and sobemovirus lineages, respectively.
      The La France isometric virus (LIV), an unclassified virus with multipartite
      dsRNA genome, is associated with a severe die-back disease of the cultivated
      mushroom. LIV appears to be of recent origin since it differs from its host in
      codon usage.

PMID- 9562898
TI  - Exploring negative dating experiences and beliefs about rape among younger and
      older women.
AB  - Although there is extensive research describing negative dating experiences and
      rape myth beliefs among university- and college-age women, there is little
      exploration of these issues among older dating women. An exploratory study that
      extends existing research by investigating rape myth beliefs and negative dating
      experiences of women ranging in age from 18 to 85 years is described.
      Participants (N = 115) completed a questionnaire which included a standardized
      measure of rape myth adherence (R-Scale; Costin, 1985), and a series of questions
      that assessed concerns about the potential for negative experiences while dating
      and actual negative dating experiences (ranging from unwanted affection to rape).
      There were remarkable similarities among younger and older women with respect to
      their dating behaviors and experiences. Women from both age groups reported being
      the target of negative dating experiences and being concerned about these
      experiences--with older women expressing slightly more concern. Older women,
      however, endorsed rape myths to a greater extent. This suggests that older women
      may be at greater risk for self-deprecation because they may be more likely to
      attribute the negative experiences they encounter to personal faults. Findings
      highlight the need for more life-span research of dating experiences and
      attitudes towards dating violence.

PMID- 9562900
TI  - Volunteer bias, sexuality, and personality.
AB  - Participants were recruited either for a study of sexual attitudes and behavior
      or for a study of attitudes and behavior without mention of sexuality. Both
      groups answered questions about their sexual behavior and completed the Self
      Monitoring Scale, the Balanced F Scale, and the Social Responsibility Scale. No
      differences were found as a function of recruitment technique in the mean reports
      of subjects' sexual behavior, but substantial differences were found in some of
      the relationships between these personality variables and sexual behavior reports
      as a function of recruitment technique; the correlation between the balanced F
      Scale score and masturbation frequency for females was +0.61 for those recruited
      for a study of sexual behavior and -0.61 for those recruited for a study of
      general attitudes and behavior. In both groups, larger correlations were found
      between female sexual behavior and personality than between male sexual behavior
      and personality. In all groups, the Self-Monitoring Scale was significantly
      correlated with masturbation frequency. The results are discussed in terms of
      self-selection bias and self-presentation bias, both of which may affect research
      on sexuality.

PMID- 9562899
TI  - Reliability and validity of self-report measures of HIV-related sexual behavior:
      progress since 1990 and recommendations for research and practice.
AB  - The trustworthiness of self-reported sexual behavior data has been questioned
      since Kinsey's pioneering surveys of sexuality in the United States (Kinsey et
      al., 1948, 1953). In the era of HIV and AIDS, researchers and practitioners have
      employed a diversity of assessment techniques but they have not escaped the
      fundamental problem of measurement error. We review the empirical literature
      produced since Catania et al.'s (1990) review regarding reliability and validity
      of self-administered and automated questionnaires, face-to-face interviews,
      telephone interviews, and self-monitoring approaches. We also provide specific
      recommendations for improving sexual behavior assessment. It is imperative that
      standardized self-report instruments be developed and used for sexual risk
      behavior assessment.

PMID- 9562901
TI  - Effects of positive and negative mood on sexual arousal in sexually functional
      males.
AB  - Effects of positive and negative musical mood induction on subjective and
      objective sexual arousal were examined in a group of sexually functional males (N
      = 24). Subjects evidenced significantly greater objective and subjective sexual
      response in the positive mood induction condition relative to both baseline and a
      neutral control condition. In contrast, the negative mood induction condition
      yielded significantly less objective sexual arousal than baseline and a neutral
      control condition. Data provide additional empirical support for the hypothesized
      impact of mood on sexual arousal.

PMID- 9562902
TI  - Endocrine therapy of transsexualism and potential complications of long-term
      treatment.
AB  - Physiological principles of the interrelationship of sex hormones and their
      regulation are the foundation of understanding appropriate treatment of the
      transsexual patient. While both genetic males and females have estrogens and
      androgens, the quantitative sex hormone production is genetically predetermined
      by sex hormone production both in the gonads and via peripheral conversion of
      hormone precursors to sex steroids. Sex hormones exert a negative feedback on the
      hypothalamus and pituitary gland whereby gonadotropin-releasing hormone (GnRH),
      pituitary luteinizing hormone (LH), and follicle-stimulating hormone (FSH) are
      regulated or suppressed by the endogenous levels of these hormones. Sex hormonal
      therapy induces attenuated GnRH stimulation of LH and FSH causing a reduction of
      serum sex hormone levels. It is clear that estrogen as well as androgen therapy
      have a dual role: (i) induction of feminization or virilization and (ii)
      suppression of the hypothalamic-pituitary-gonadal axis leading to a reduction of
      endogenous estradiol or testosterone secretion. Cross-sex hormonal treatment may
      have substantial medical side effects. The smallest dosage of hormonal therapy
      compatible with the above clinical aims should be used.

PMID- 9562903
TI  - Evidence for interactions between rat hepatoma cell apoptosis and
      differentiation.
AB  - Partial copper depletion of a variant rat hepatoma cell line induces a transient
      inhibition of growth and the genesis of stable, well-differentiated revertants.
      We report a burst of cell death, synchronous with the peak of reversion. The
      characteristics of this cell mortality were typical of apoptosis and included
      detachment from the plastic support, chromatin condensation and fragmentation,
      and internucleosomal DNA degradation. Although commitment to cell death was
      induced by copper deficiency, the apoptotic process was partially inhibited as
      assessed from electrophoretic patterns of DNA degradation. Redifferentiation was
      closely linked to the apoptotic death program. Analysis of rescued detached cells
      in all three media (standard, Cu-, Fe-) indicated that the frequency of
      revertants was significantly higher among floating as opposed to adherent cell
      populations. Nevertheless, experimental copper depletion increased by 10(4) times
      the revertant frequency among adherent cells. We propose that redifferentiation
      of the variant hepatoma cells (and concomitant recovery of tumorigenicity) is
      determined by the gene expression pattern of programmed cell death.

PMID- 9562904
TI  - Isolation of protease-free alcohol dehydrogenase (ADH) from Drosophila simulans
      and several homozygous and heterozygous Drosophila melanogaster variants.
AB  - The enzyme alcohol dehydrogenase (ADH) from several naturally occurring ADH
      variants of Drosophila melanogaster and Drosophila simulans was isolated.
      Affinity chromatography with the ligand Cibacron Blue and elution with NAD+
      showed similar behavior for D. melanogaster ADH-FF, ADH-71k, and D. simulans ADH.
      Introduction of a second Cibacron Blue affinity chromatography step, with
      gradient elution with NAD+, resulted in pure and stable enzymes. D. melanogaster
      ADH-SS cannot be eluted from the affinity chromatography column at a high
      concentration of NAD+ and required a pH gradient for its purification, preceded
      by a wash step with a high concentration of NAD+. Hybrid Drosophila melanogaster
      alcohol dehydrogenase FS has been isolated from heterozygous flies, using
      affinity chromatography with first elution at a high concentration NAD+, directly
      followed by affinity chromatography elution with a pH gradient. Incubation of
      equal amounts of pure homodimers of Drosophila melanogaster ADH-FF and ADH-SS, in
      the presence of 3 M urea at pH 8.6, for 30 min at room temperature, followed by
      reassociation yielded active Drosophila melanogaster ADH-FS heterodimers. No
      proteolytic degradation was found after incubation of purified enzyme
      preparations in the absence or presence of SDS, except for some degradation of
      ADH-SS after very long incubation times. The thermostabilities of D. melanogaster
      ADH-71k and ADH-SS were almost identical and were higher than those of D.
      melanogaster ADH-FF and D. simulans ADH. The thermostability of D. melanogaster
      ADH-FS was lower than those of D. melanogaster ADH-FF and ADH-SS. D. melanogaster
      ADH-FF and ADH-71k have identical inhibition constants with the ligand Cibacron
      Blue at pH 8.6, which are two times higher at pH 9.5. The Ki values for D.
      simulans ADH are three times lower at both pH values. D. melanogaster ADH-SS and
      ADH-FS have similar Ki values, which are lower than those for D. melanogaster ADH
      FF at pH 8.6. But at pH 9.5 the Ki value for ADH-FS is the same as at pH 8.6,
      while that of ADH-SS is seven times higher. Kinetic parameters of Drosophila
      melanogaster ADH-FF, ADH-SS, and ADH-71k and Drosophila simulans ADH, at pH 8.6
      and 9.5, showed little or no variation in K(m)eth values. The K(m)NAD values
      measured at pH 9.5 for Drosophila alcohol dehydrogenases are all lower than those
      measured at pH 8.6. The rate constants (kcat) determined for all four Drosophila
      alcohol dehydrogenases are higher at pH 9.5 than at pH 8.6. D. melanogaster ADH
      FS showed nonlinear kinetics.

PMID- 9562905
TI  - Modeling studies of conformational changes in the substrate-binding loop in
      Drosophila alcohol dehydrogenase.
AB  - Three-dimensional structures of seven short-chain dehydrogenases/reductases show
      that these enzymes share common structural features. Sequence alignment studies
      of Drosophila alcohol dehydrogenase (DADH), with an unknown 3D-structure, and
      four short-chain dehydrogenases/reductases with known X-ray structures suggest
      that DADH shares the same structural features. However, the substrate binding
      regions, which are located in the C-terminal region of these enzymes, share
      little sequence homology, because of the wide variety of substrates used. X-ray
      structures of short-chain dehydrogenases/reductases indicate that conformational
      changes occur in a loop, in the C-terminal region, upon substrate binding. This
      substrate-binding loop is located between a strand and a helix and may contain
      one or two small helices. Secondary structure predictions and modeling studies of
      this substrate-binding loop in DADH predict that the two helices may also be
      present in this enzyme. The naturally occurring variants of Drosophila
      melanogaster alleloenzymes ADH-S and ADH-F differ in a replacement of threonine
      by lysine at position 192, which is located at a central position in the
      substrate-binding loop. The positive charge of lysine may move significantly on
      substrate binding, resulting in a direct charge interaction with NAD+ in the
      enzyme-substrate complex, explaining a very strong influence of pH on the binding
      of ADH-S for the NAD+ analogue Cibacron Blue. This indicates that the ADH S/F
      polymorphism has a direct influence on the catalytic properties of the enzyme.

PMID- 9562907
TI  - Rapid genotyping of mice with hemoglobinopathies and globin transgenes.
AB  - The hematology of the laboratory mouse has been well characterized. Normal
      genetic differences at the alpha- and beta-globin gene loci serve as useful
      markers for a wide variety of types of experimental studies. There are a number
      of naturally occurring or induced mutations that disrupt globin expression and
      produce thalassemic phenotypes. In addition, much has been learned of the
      workings of the globin locus control region from studies of transgenic mice,
      including those with mutations induced by targeted site-specific modifications.
      After a new mutation or transgene has been created, it must be maintained in
      living mice, and the genotypes of the offspring must be ascertained. While it is
      possible to determine genotypes by DNA analyses, such assays are time consuming
      and relatively expensive. An osmotic challenge test--originally developed for the
      genotyping of large-deletion alpha-thalassemia mutations in mice--has proven
      useful in detecting both severe and milder alpha- and beta-thalassemias, as well
      as some transgenic genotypes in mice carrying human globin genes. Reliable
      genotyping can, in some cases, be completed within a few minutes with minimal
      expense. Quantification of red cell fragility for a variety of thalassemic and
      transgenic mice is described here, along with a simplified test suitable for
      rapid, routine genotyping. The osmotic challenge test is perfectly reliable for
      distinguishing genotypes that cause significantly decreased release of hemoglobin
      from the red cells, but it is also useful for some of the conditions in which
      overall erythrocyte osmotic fragility is essentially normal.

PMID- 9562906
TI  - A family of Drosophila genes encoding quaking-related maxi-KH domains.
AB  - We recently identified a Drosophila gene, wings held out (who), that specifies a
      STAR (signal transduction and RNA activation) protein expressed within mesoderm
      and muscles. Genetic evidence suggests that WHO regulates muscle development and
      function in response to steroid hormone titer. who is related to the mouse
      quacking gene, essential for embryogenesis and neural myelination, and gld-1, a
      nematode tumor suppressor gene necessary for oocyte differentiation, both of
      which contain RNA binding "maxi-KH" domains presumed to link RNA metabolism to
      cell signaling. To initiate a broader study of Drosophila WHO-related proteins we
      used degenerate primers encoding peptides unique to maxi-KH domains to amplify
      the corresponding genes. We recovered nine genes, all specifying single maxi-KH
      domain proteins having tripartite regions of similarity that extend over 200
      amino acids. One is located within the 54D chromosome subdivision, and one within
      58C, while the remaining seven are within the 58E subdivision. At least four of
      these STAR proteins are expressed in a general manner, suggesting that maxi-KH
      domains are employed widely in Drosophila.

PMID- 9562908
TI  - Prediction of employment outcome one to three years following traumatic brain
      injury (TBI).
AB  - The current study investigated the relationship between age, education (EDUC),
      pre-injury productivity (PIP), Glasgow Coma Scale score, and a functional rating
      score at admittance and discharge from rehabilitation (Disability Rating Scale
      [DRS]) to employment status at one to three years following traumatic brain
      injury. EDUC, admit DRS, discharge DRS, and PIP all correlated significantly with
      follow-up employment status, 0.29, -0.32, -0.36, and 0.25 respectively. All
      possible combinations were then evaluated by Mallow's Cp statistic. The best
      fitting model was then used in a discriminant function analysis. The discriminant
      function correctly classified 84% of the employed subjects, 66% of the
      unemployed, and 75% across both groups. The current results compare favourably
      with those obtained in previous studies.

PMID- 9562909
TI  - Traumatic brain injury and posttraumatic stress disorder: a preliminary
      investigation of neuropsychological test results in PTSD secondary to motor
      vehicle accidents.
AB  - This study investigated the effect of traumatic brain injury on the development
      of posttraumatic stress disorder (PTSD). Subjects were 107 motor vehicle accident
      survivors including 38 individuals who were diagnosed with posttraumatic stress
      disorder (PTSD). Neuropsychological testing was administered to all subjects
      during an initial diagnostic evaluation. Results showed that subjects who had
      lost consciousness during their MVA had greater impairment on speed dependent
      tests and delayed recall of verbal material. Subjects who suffered traumatic
      brain injury (TBI) were also found to have developed PTSD as often as those who
      had not reported TBI. Implications for future research and clinical utility are
      discussed.

PMID- 9562910
TI  - Detecting malingered memory deficits with the Recognition Memory Test.
AB  - The purpose of the present study was to examine the efficacy of using the
      Recognition Memory Test (RMT) as a marker for malingered memory deficits. Data
      from 60 subjects, including 40 patients seen for neuropsychological evaluation
      and 20 university undergraduates, are reported. The university students were
      given experimental instructions to malinger. Students were compared to 20 memory
      impaired and 20 memory-nonimpaired patients. The students who were instructed to
      malinger memory impairment performed more poorly than both groups of patients.
      Discriminant function analyses using the two scores derived from the RMT as
      predictors of group membership resulted in a 100% initial correct classification
      rate and a 96.7% correct classification rate on cross-validation.

PMID- 9562911
TI  - Traumatic brain injury in childhood: intellectual, behavioural and social outcome
      into adulthood.
AB  - In order to obtain indicative data regarding intellectual, behavioural and social
      outcome into adulthood of subjects with a history of childhood head injury (CHI),
      twenty adults were selected who had been referred to the Neuropsychology Unit at
      the University of Parma at the time of a traumatic brain injury (TBI) at an age
      between 8 and 14 years. The level of intellectual and behavioural impairment was
      determined and rated by WISC and WAIS IQa and by the frequency of maladjustive
      behaviour. GOS score and Barthel index were used to detect the level of
      disability. Social adjustment and community integration were determined by the
      Social Adjustment Scale (SAS) and the Community Integration Questionnaire (CIQ)
      respectively. Results indicate that (1) subjects who suffer a severe CHI present
      a higher pre-injury incidence of character disturbances than the normal
      population and injury-related difficulties to socialize which persist long-term
      and add to other problems; (2) even though intellectual and functional sequelae
      are frequent in these children in adulthood and do not improve in their
      correlation to age, these do not appear to be the prevailing problems and (3) the
      prevailing problems seem to be social maladjustment and poor quality of life,
      which are still present several years post-injury and seem to be related to
      behavioural and psychosocial disorders in spite of an increased ADL-functioning.
      This has already been clearly demonstrated in the case of adulthood trauma.

PMID- 9562912
TI  - Old warp, new weft: weaving a new life fabric after anoxia.
AB  - A young New Zealander reweaves a new life after a severe anoxic brain injury. His
      mother, a teacher, works from an educational perspective to construct an
      individualized lifestyle plan (ILP), implemented in the community by a team of
      support workers. This approach to learning is holistic and encompasses the
      physical, cognitive, emotional and spiritual dimensions of human healing. This
      article, part of the requirements for a Master's degree in Special Education,
      recounts part of the new journey, which is described in the language of capacity,
      achievement and love, rather than that of dysfunction, disability and
      disappointment.

PMID- 9562913
TI  - Construct validation of the Hoensbroeck Disability Scale for Brain Injury in
      acquired brain injury rehabilitation.
AB  - PURPOSE: To evaluate the construct validity of the Hoensbroeck Disability Scale
      for Brain Injury (HDSB) against the Disability Rating Scale (DRS). METHODS: The
      HDSB was correlated with the DRS at admission, 6 weeks later and at discharge in
      33 brain injured patients during post-acute rehabilitation. Next, to study the
      longitudinal construct validity of the HDSB the mean changes in score of the HDSB
      and the DRS were correlated. Finally, the sensitivity to change over a 6-week
      period was evaluated by comparison of the effect sizes of the HDSB scores with
      the DRS scores. RESULTS: The HDSB subscales correlate high and in the expected
      direction with the DRS at all three points in time. The correlation of the
      changes between HDSB and DRS is moderate, but in the expected direction. The
      sensitivity to change in time of the HDSB is lower than that of the DRS.
      CONCLUSIONS: This study supports the validity of the HDSB as an instrument to
      describe the disability of acquired brain injury patients at a single point in
      time. Its ability to measure changes in disability over time is questionable and
      needs further investigation.

PMID- 9562914
TI  - Educational outcome for secondary and postsecondary students following traumatic
      brain injury.
AB  - During the 12 month period of January-December 1991, 75 admissions were made to
      the Head Injury Unit at Bethesda Hospital, Melbourne, Australia. Approximately
      26% (20) of these admissions were either secondary or postsecondary students.
      Thirteen of the 20 students were interviewed by telephone at approximately 3
      years postinjury and demographic and medical information were obtained from their
      medical files. Outcome was documented in three areas: educational, medical and
      psychosocial status. At 3 years postinjury, 11 subjects (85%) had either
      completed a course or were still studying. The average time for students to
      return to study was approximately 11 months postinjury. The students reported a
      number of changes including: enrollment in different courses, a reduction in
      course load to part-time study, altered educational and vocational goals and an
      increased need to utilize study skill strategies, individual tuition and special
      consideration. In addition, students reported changes to their relationships with
      peers and their involvement in extracurricular activities. It is apparent from
      these results that a number of factors need to be considered when a student is
      planning to return to study following TBI and that a range of support services
      may be required. Future studies are needed to examine the factors which impede or
      enhance a student's progress following TBI.

PMID- 9562915
TI  - Improvement during baseline: three case studies encouraging collaborative
      research when evaluating caregiver training.
AB  - The trend in cognitive rehabilitation toward reduced services, which provide more
      functionally relevant outcomes and the recognition of limited maintenance and
      generalization with many existing interventions, challenges current research
      models. There is a need to develop and evaluate interventions that can be
      implemented by persons other than rehabilitation professionals and that are well
      suited to naturalistic settings. The researchers responded to these challenges by
      designing a series of single subject experiments evaluating the effectiveness of
      training caregivers to provide appropriate cognitive support to persons with
      brain injury within their own natural living environments. The goal of the
      original research project included evaluating a collaborative mode of interaction
      with the subjects and their support persons (as opposed to traditional directive
      treatment models) where the caregivers and subjects were instrumental in
      designing the intervention and collective performance data. This paper presents
      the data from the initial three subject/caregiver groups all of whom demonstrated
      improvement in the target behaviours during the baseline period. It appeared that
      the act of measuring client performance changed the behaviours of the support
      persons and resulted in positive changes in baseline levels. The research and
      clinical implications of these findings are discussed.

PMID- 9562916
TI  - Circadian regulation of a plant protein kinase.

PMID- 9562918
TI  - Effects of SCN lesions on circadian blood pressure rhythm in normotensive and
      transgenic hypertensive rats.
AB  - Transgenic hypertensive TGR(mREN2)27 (TGR) rats, carrying an additional mouse
      renin gene, have been found to show inverse circadian blood pressure profiles
      compared to normotensive Sprague-Dawley rats. In order to evaluate the
      contributions of the suprachiasmatic nucleus (SCN) and the neurohormone melatonin
      to cardiovascular circadian regulation in TGR(mREN2)27 rats and Sprague-Dawley
      (SPRD) controls, we investigated the effects of melatonin agonist and antagonist
      treatment in SCN-lesioned and nonlesioned rats, which were kept under conditions
      of alternating light and darkness (LD). After destruction of the SCN, circadian
      rhythmicity in blood pressure, heart rate (HR), and motor activity (MA) was
      almost abolished in rats of both strains. One week of treatment with a synthetic
      melatonin agonist S-21634 was not able to restore circadian variation in the
      parameters monitored. In nonlesioned TGR(mREN2)27 rats and Sprague-Dawley control
      rats, the melatonin antagonist S-22365 had no suppressive effect on LD
      synchronized circadian rhythmicity, indicating that LD itself may have a stronger
      influence on the SCN than endogenous melatonin.

PMID- 9562917
TI  - Oviposition in the period genotypes of Drosophila melanogaster.
AB  - Two behavioral rhythm phenotypes, oviposition and locomotor activity, have been
      compared in the four period genotypes (per+, pers, per0, and per1) of Drosophila.
      Period, signal-to-noise ratio, and phase were all analyzed and the genetic
      penetrance of the two characters was estimated. Significant rhythmicity of both
      oviposition and locomotor activity was evident in all four genotypes. The
      entrained and free-running periods of the activity rhythms of per+, pers, and
      per1 were within the range reported for these flies by previous workers, and
      rhythmic behavior was also shown by the per0 flies. The free-running period of
      the oviposition rhythm varied similarly between the four genotypes and showed
      significant correlation with that of the locomotor activity rhythm. It is
      suggested that both rhythm phenotypes are determined by the period gene, and
      estimates of the genetic penetrance of rhythmicity in oviposition and locomotor
      activity, based on period and signal-to-noise ratios (SNRs) of the different
      strains, are consistent with this hypothesis. The phase of maximum oviposition
      and locomotor activity showed greater variability between the genotypes and was
      not significantly correlated with period, suggesting that this rhythm
      characteristic is independent of mutations at the period locus.

PMID- 9562919
TI  - Revolutionary science: an improved running wheel for hamsters.
AB  - Golden hamsters, Mesocricetus auratus, ran more in wheels with the floor covered
      by a plastic mesh than in wheels with the usual rods. This preference was evident
      both in tests with a single wheel and in tests when the animals were offered a
      choice between two wheels. Phase shifts following a 3h confinement to a novel
      wheel were greater if the novel wheel had the plastic cover.

PMID- 9562920
TI  - In vitro susceptibility rhythms. II. Biological-time-dependent differences in
      effect of beta 1- and beta 2-adrenergic agonists of rat aorta and influence of
      endothelium.
AB  - Time-dependent variations in the vasodilator effects of beta-adrenergic agonists
      terbutaline (Ter) and dobutamine (Dob) were studied in isolated rings of rat
      thoracic aorta in both endothelium-intact and endothelium-denuded preparations.
      Rats were housed in light from 08:00 to 20:00 and in darkness from 20:00 to 08:00
      and sacrificed at six different times of the day. In endothelium-intact and
      endothelium-denuded aortic rings precontracted submaximally with phenylephrine
      (Phe), addition of Ter and Dob produced concentration-dependent relaxations.
      Removal of endothelium reduced the relaxant responses and area under curve (AUC)
      values and augmented the EC50 values to Ter and Dob at most, but not all, time
      points. Two-way analysis of variance (ANOVA) revealed that AUCs, maximum
      responses, and EC50 values significantly depended on both treatment (endothelium
      intact/endothelium denuded) and time of sacrifice. Results of the present study
      clearly show that in vitro sensitivity of rat thoracic aorta to beta-adrenergic
      agonists displays temporal variations depending on the time of animal sacrifice,
      and the presence of endothelium modifies the rhythmicity in beta-adrenergic
      activity. These variations may be due to the circadian rhythmicity in the
      adenylyl cyclase-cAMP-phosphodiesterase system that mediates the responses to
      beta-adrenergic agonists.

PMID- 9562921
TI  - Effect of captopril on the time-dependent variation of kaolin-induced writhing
      reaction.
AB  - Effect of captopril, an angiotensin-converting enzyme (ACE) inhibitor, on the
      time-dependent variation of kaolin-induced writhing reactions was examined in
      mice kept under conditions of light from 07:00 to 19:00 and dark from 19:00 to
      07:00. The number of writhes was counted for 60 minutes after a single
      intraperitoneal injection of kaolin at 01:00, 07:00, 13:00, and 19:00. The number
      of writhes showed a time-dependent variation, with a peak at 19:00 and a trough
      at 07:00 in the control group. Captopril significantly increased the number of
      writhes after dosing at 01:00 and 07:00 (during the active period). The ACE
      activity following captopril dosing was significantly lower in the 07:00 than the
      19:00 trial. These results suggest that the pharmacological effect of captopril
      varies with the dosing time, and the enhancement of the kaolin-induced writhing
      reaction is greater following dosing of the agent at nighttime in mice.

PMID- 9562922
TI  - Evaluating the role of melatonin in the long-term treatment of delayed sleep
      phase syndrome (DSPS).
AB  - Delayed sleep phase syndrome (DSPS) involves a mismatch between the usual daily
      schedule required by the individual's environment and his or her circadian sleep
      wake pattern. Patients suffering from DSPS are treated with chronotherapy, light
      therapy, or melatonin administration. While chronotherapy and light therapy are
      demanding and difficult treatments that usually lead to compliance problems,
      melatonin administration is a relatively simple and easy treatment option.
      Previous studies carried out on relatively small samples of DSPS patients have
      shown that melatonin has a sleep-promoting and entraining action when taken in
      the evening. The present study, which accompanied routine treatment in our sleep
      clinic, examined the efficiency of melatonin treatment in a relatively large
      population of DSPS subjects by means of subjective reports. The 61 subjects, 37
      males and 24 females, were diagnosed with DSPS by means of clinical assessment
      and actigraphy at our sleep clinic. Their mean pretreatment falling asleep and
      waking times were 03:09 (SD = 86.22 minutes) and 11:31 (SD = 98.58 minutes),
      respectively. They were treated with a 6-week course of 5 mg of oral melatonin
      taken daily at 22:00. A survey questionnaire was sent to the home of each subject
      12-18 months after the end of the treatment; the survey investigated the
      efficiency of the melatonin treatment and its possible side effects. Of the
      patients, 96.7% reported that the melatonin treatment was helpful, with almost no
      side effects. Of these, 91.5% reported a relapse to their pretreatment sleeping
      patterns within 1 year of the end of treatment. Only 28.8% reported that the
      relapse occurred within 1 week. The pretreatment falling asleep and waking times
      of patients in whom the changes were retained for a relatively long period of
      time were significantly earlier than those of patients whose relapse was
      immediate (t = 2.18, p < .05; t = 2.39, p < .05, respectively), with no
      difference in sleep duration. The implications of these findings, as well as
      further research possibilities, are discussed.

PMID- 9562923
TI  - Inferential statistical method for analysis of nonsinusoidal hybrid time series
      with unequidistant observations.
AB  - Most variables of interest in laboratory medicine show predictable changes with
      several frequencies in the span of time investigated. The waveform of such
      nonsinusoidal rhythms can be well described by the use of multiple components
      rhythmometry, a method that allows fitting a linear model with several cosine
      functions. The method, originally described for analysis of longitudinal time
      series, is here extended to allow analysis of hybrid data (time series sampled
      from a group of subjects, each represented by an individual series). Given k
      individual series, we can fit the same linear model with m different frequencies
      (harmonics or not from one fundamental period) to each series. This fit will
      provide estimations for 2m + 1 parameters, namely, the amplitude and acrophase of
      each component, as well as the rhythm-adjusted mean. Assuming that the set of
      parameters obtained for each individual is a random sample from a multivariate
      normal population, the corresponding population parameter estimates can be based
      on the means of estimates obtained from individuals in the sample. Their
      confidence intervals depend on the variability among individual parameter
      estimates. The variance-covariance matrix can then be estimated on the basis of
      the sample covariances. Confidence intervals for the rhythm-adjusted mean, as
      well as for the amplitude-acrophase pair, of each component can then be computed
      using the estimated covariance matrix. The p-values for testing the zero
      amplitude assumption for each component, as well as for the global model, can
      finally be derived using those confidence intervals and the t and F
      distributions. The method, validated by a simulation study and illustrated by an
      example of modeling the circadian variation of heart rate, represents a new step
      in the development of statistical procedures in chronobiology.

PMID- 9562924
TI  - The National Aboriginal Achievement Awards. Dr. Cornelia Wieman is the 1998
      medical award recipient.

PMID- 9562926
TI  - Neutropenic complications in advanced-stage non-Hodgkin's lymphoma: implications
      for the use of prophylactic recombinant human granulocyte-colony stimulating
      factor (G-CSF).
AB  - OBJECTIVES: To determine the incidence of neutropenic complications in patients
      receiving chemotherapy for advanced-stage non-Hodgkin's lymphoma (NHL), to
      predict which patients are at high risk for neutropenic complications and to
      develop an economic model for subsequent testing to assess the potential cost
      effectiveness of prophylactic treatment with recombinant human granulocyte-colony
      stimulating factor (G-CSF). DESIGN: Retrospective chart review. PATIENTS: Forty
      two patients with advanced-stage NHL treated at the Tom Baker Cancer Centre,
      Calgary, between Jan. 1, 1992, and Dec. 31, 1993. OUTCOME MEASURES: Neutropenic
      complications including incidence of febrile neutropenic events, documented
      infections, and chemotherapy dose delays or dose reductions. RESULTS: Of the 42
      patients, 8 (19%) experienced febrile neutropenic events and 18 (43%) required
      chemotherapy dose modifications (delays or reductions or both) because of
      neutropenia. Fifteen patients (36%) were identified as being at high risk for
      neutropenic complications and may have benefited from the administration of
      prophylactic G-CSF. An economic model developed to assess the potential cost
      effectiveness of prophylactic G-CSF therapy estimated that, for high-risk
      patients, the theoretical incremental cost per life year saved was $3300.
      CONCLUSIONS: Febrile neutropenia and infection cause significant morbidity and
      mortality in patients receiving combination chemotherapy for the treatment of
      advanced-stage NHL. Secondary prophylactic G-CSF therapy has been proven to
      decrease the incidence of febrile neutropenia and infection in these patients.
      Considering the reduction in neutropenic complications and resulting increase in
      chemotherapy dose intensity received by patients on G-CSF, the theoretical
      incremental cost per life year saved of $3300 with G-CSF therapy is relatively
      low compared with other medical interventions.

PMID- 9562925
TI  - Long-term regulation of leptin expression is correlated with adipocyte number in
      obese rats.
AB  - OBJECTIVE: To investigate long-term regulation of leptin expression in adipose
      tissues of obese JCR:LA-corpulent rats, which have been shown to overexpress
      leptin. DESIGN: Manipulation of adipose tissue growth in obese rats by dietary
      restriction. INTERVENTIONS: Weanling female obese rats were maintained on 1 of 3
      diets until 8 months old. One group was allowed to feed ad libitum, the second
      was pair-fed with lean rats, and the third had food intake restricted to maintain
      weights equal to those of age-matched lean rats. OUTCOME MEASURES: Body and fat
      pad weights, leptin messenger RNA (mRNA) levels, and size and number of
      adipocytes in retroperitoneal fat pads. RESULTS: Adipose tissue mass was
      increased 6-fold in the obese rats compared with the lean ones, despite equal
      body weight and intake restriction that was sufficient to impair growth. Although
      leptin mRNA level was down-regulated by intake restriction, it was still twice as
      elevated in the obese rats as in the lean ones, and was highly correlated with
      specific fat pad mass and adipocyte number, but not with size. CONCLUSIONS: These
      data suggest that leptin expression is correlated with adipocyte number within a
      fat pad, and that there is inappropriate hepatic de novo synthesis and storage of
      triacylglycerols in obese rats. A role for leptin in nutrient partitioning is
      proposed.

PMID- 9562927
TI  - Different effects of heparin in males and females.
AB  - OBJECTIVE: To determine whether women have a Pharmacological predisposition to
      bleeding and a worse outcome than men during heparin therapy, in light of recent
      studies showing that women have a higher risk of bleeding complications following
      anticoagulant therapy for thrombotic disorders than men. DESIGN: Prospectively
      planned subgroup analysis of a double-blind randomized study. SETTING: Academic
      tertiary care hospitals in Hamilton, Ont. PATIENTS: A total of 199 consecutive
      patients (105 women, 93 men) presenting with proximal deep vein thrombosis. (One
      patient was not included due to incomplete data). OUTCOME MEASURES: Activated
      partial thromboplastin time (APTT) values and heparin levels were assessed every
      4 to 6 hours after a standard heparin bolus and infusion. The effect of sex on
      heparin doses and levels was also assessed after stable therapeutic heparin
      infusions were achieved. RESULTS: The women had higher heparin levels than the
      men (0.560 [standard error of the mean, SEM 0.056] units/mL v. 0.347 [SEM 0.062]
      units/mL, p < 0.0001) and higher APTT values (94.9 [SEM 0.50] seconds v. 81.2
      [SEM 0.53] seconds, p = 0.0002) 4 to 6 hours after being given the same heparin
      bolus and infusion doses. After achieving therapeutic APTT values, the women
      received lower heparin doses than the men (27.9 [SEM 0.24] 1000 units/24 hours v.
      34.5 [SEM 0.24] 1000 units/24 hours, p < 0.0001) but had higher heparin levels
      (0.349 [SEM 0.035] units/mL v. 0.292 [SEM 0.036] units/mL, p = 0.034). The effect
      of sex was also determined after correcting for the known effects of weight and
      age on heparin therapy. After adjusting for patient weight, among the women,
      older women had higher heparin levels but, among the men, there was little effect
      of age. There were no sex differences with respect to bleeding complications or
      recurrent thromboembolic disease. CONCLUSION: Women showed alterations in the
      pharmacokinetics of heparin, which could explain a predisposition to bleeding
      complications. Under the heparin protocol used in this study, heparin doses were
      rapidly adjusted, which may explain why rates of bleeding complications and
      recurrent thromboembolism were similar in men and women. We do not recommend
      changes in heparin therapy based on these results, but suggest the use of
      protocols that assess coagulation parameters frequently and then adjust heparin
      doses rapidly, in order to individualize therapy. Further study is required to
      determine whether there are sex differences in bleeding complications associated
      with anticoagulant therapy, and to confirm the altered pharmacokinetics of
      heparin in women.

PMID- 9562928
TI  - Exercise capacity and energy expenditure of morbidly obese and previously obese
      subjects.
AB  - OBJECTIVE: To determine whether morbidly obese and previously obese women fail to
      lose weight after gastric bypass surgery because of reduced energy expenditure,
      and whether a large, surgically induced, rapid weight loss improves exercise
      capacity on a treadmill. DESIGN: Cross-sectional study. PARTICIPANTS: Four groups
      of 5 subjects: 1) patients still obese 12 months after surgery (failure); 2)
      patients who achieved normal weight after surgery (success); 3) obese patients
      who had not yet undergone surgery (preoperative); and 4) nonobese (control)
      subjects. Four subjects in the preoperative group were studied again at 6 months
      postsurgery. MAIN OUTCOME MEASURES: Total daily energy expenditure (TDEE), and
      exercise capacity and peak oxygen consumption (VO2) during treadmill exercise.
      RESULTS: TDEE or energy expenditure (EE) above basal metabolic rate (when
      normalized for body size) was similar for all groups, but the absolute energy
      consumption was higher in the preoperative and failure groups. Treadmill
      endurance time was greater in the success than the failure and preoperative
      groups, and the endurance times of these 3 groups were less than those of the
      nonobese subjects. Peak VO2 body weight was similar in the success, failure and
      preoperative groups, which meant that the peak VO2 was lower in the success group
      than in the preoperative and failure groups. Six months after surgery, peak VO2
      had not decreased in the preoperative group. CONCLUSION: Failure to lose weight
      after isolated gastric bypass surgery was not because of a lower level of
      activity. Aerobic capacity was impaired 1 year, but not 6 months, after a large
      weight loss. Exercise training may be appropriate to maintain absolute peak
      oxygen consumption.

PMID- 9562929
TI  - Uncertainties in bone mineral density T scores.
AB  - In the diagnosis and management of osteopenia and osteoporosis, dual photon
      absorptiometric measurements of lumbar spine and proximal femur bone mineral
      density are interpreted by calculating a T score, which is the number of standard
      deviations by which a result deviates from the mean bone density in young adults
      of the same sex. Threshold values are then used to categorize patients as having
      osteopenia or osteoporosis. The uncertainty associated with a single bone mineral
      density measurement, as well as the uncertainties in the assumed values for the
      bone mineral density in young adults and the population standard deviation,
      combine to create an uncertainty in the calculated T score. It is estimated that
      95% of bone density measurements have a T score uncertainty of less than 0.4.
      This means that a single measurement of bone mineral density should not be used
      in isolation to assign a given patient to a specific diagnostic category. Rather,
      a bone mineral density measurement should be regarded as only one of the
      variables that determine the risk of fracture in a given patient.

PMID- 9562930
TI  - Bone mineral density T scores: assessing the risk.

PMID- 9562931
TI  - New concept for treatment of acute myocardial ischemia.

PMID- 9562932
TI  - Are technetium-99m-labeled myocardial perfusion agents adequate for detection of
      myocardial viability?
AB  - The noninvasive assessment of myocardial viability in patients with coronary
      artery disease and depressed left ventricular function has proven clinically
      useful for identifying those patients with ischemic cardiomyopathy who benefit
      most from coronary revascularization. Thallium-201 (201Tl) imaging at rest has
      been the radionuclide imaging technique most often utilized for distinguishing
      viable myocardium from scar. However, new technetium-99m (99mTc) perfusion agents
      such as 99mTc-sestamibi and 99mTc-tetrofosmin have emerged as alternatives to
      201Tl for imaging of regional myocardial perfusion. Whether these new agents,
      which have better physical properties for imaging with a gamma camera than 201Tl,
      are valid for use in assessing myocardial viability is still uncertain. Recent
      clinical studies have demonstrated that these agents, when imaged using
      quantitative SPECT, can identify patients with myocardial hibernation who exhibit
      improved regional systolic function following revascularization. Experimental
      laboratory studies have shown that the uptake of 99mTc-sestamibi and 99mTc
      tetrofosmin in ischemic myocardium is only slightly lower than the uptake of
      201Tl. These 99mTc-labeled agents remain bound intracellularly in mitochondria of
      viable myocytes under conditions of myocardial stunning and short-term
      hibernation, producing severe myocardial asynergy. With respect to determination
      of viability, the inferior wall region is at times problematic since attenuation
      of 99mTc-sestamibi and 99mTc-tetrofosmin is greatest in this area. Demonstration
      of preserved systolic thickening on ECG-gated SPECT images is indicative of
      viability in the instance of decreased regional 99mTc counts due to attenuation
      and not scar. Administration of nitrates prior to tracer injection improves the
      sensitivity for identifying viable myocardial segments using rest imaging with
      99mTc-sestamibi or 99mTc-tetrofosmin. Thus, it appears that the new 99mTc
      perfusion imaging agents can be successfully employed for the determination of
      myocardial viability in the setting of severe regional dysfunction and chronic
      coronary artery disease. The greater the myocardial uptake of these agents in the
      resting state, the greater the probability of improved systolic function after
      coronary revascularization.

PMID- 9562933
TI  - Prinzmetal's variant angina.
AB  - Although the prevalence of variant angina pectoris is unknown, it appears to be
      substantially less common than typical, exertional angina and unstable angina at
      rest. The patient with variant angina typically complains of a pressure-like,
      squeezing retrosternal chest discomfort of several minutes duration. The
      diagnosis is secured by the occurrence of transient ST-segment elevation in
      association with chest pain, both of which resolve spontaneously or with
      nitroglycerin. After the diagnosis is made, the patient usually becomes symptom
      free on calcium-channel blockers with or without long-acting nitrates. Although
      the long-term survival of these patients is excellent, an occasional individual
      with variant angina sustains a complication, most often myocardial infarction, a
      life-threatening arrhythmia, or sudden cardiac death.

PMID- 9562934
TI  - Comparison of transesophageal Doppler coronary flow reserve measurements with
      thallium-201 single-photon emission computed tomography imaging in assessment of
      left anterior descending artery stenoses.
AB  - BACKGROUND AND HYPOTHESIS: Recent studies demonstrate the feasibility of coronary
      flow reserve measurements by transesophageal echocardiographic (TEE) Doppler
      recordings of coronary sinus or left anterior descending (LAD) coronary artery
      flow velocity for detecting stenoses of the LAD artery. This study compares
      coronary flow reserve measurements by Doppler TEE with thallium-201 (201Tl)
      single-photon emission computed tomography (SPECT) in patients with proximal
      single-vessel LAD stenosis. METHODS: Nineteen patients with various degrees of
      LAD stenosis (mean area stenosis 71 +/- 24%; range 24-96%) were studied. Area
      stenosis by quantitative coronary angiography was < 75% in 7 patients and > 75%
      in 12 patients. Transesophageal LAD and coronary sinus Doppler measurements were
      performed at baseline and after intravenous dipyridamole. Coronary flow reserve
      was calculated as the ratio of hyperemic to baseline average peak velocities.
      Predefined coronary flow reserve cut-off values of 1.8 for the coronary sinus
      method and of 2.0 for the LAD method were used for diagnosis of significant LAD
      stenosis. Results were compared with qualitative 201Tl dipyridamole SPECT.
      RESULTS: Overall predictive accuracy for diagnosis of > 75% LAD stenosis was 79%
      for 201Tl SPECT, 77% for the transesophageal LAD and 79% for the transesophageal
      coronary sinus technique. Concordant results between 201Tl SPECT and the LAD and
      coronary sinus Doppler methods were observed in 79% and 71% of patients,
      respectively. CONCLUSIONS: Thallium-201 SPECT and transesophageal Doppler
      assessment of coronary flow reserve have similar accuracy for diagnosing
      significant proximal LAD stenosis. Therefore, both transesophageal Doppler
      techniques might constitute another widely available, noninvasive method for
      assessment of left coronary artery disease, if disease location is proximal.

PMID- 9562935
TI  - Prognostic value of predischarge radionuclide ventriculography at rest and
      exercise after acute myocardial infarction treated with thrombolytic therapy or
      primary coronary angioplasty. The Zwolle Myocardial Infarction Study Group.
AB  - BACKGROUND: Previous studies have demonstrated the prognostic value of
      radionuclide ventriculography at rest and exercise in patients post myocardial
      infarction (MI). The number of studies in patients treated with modern
      reperfusion techniques, including thrombolysis or primary angioplasty, however,
      is limited. HYPOTHESIS: The aim of this study was to evaluate the prognostic
      significance of predischarge radionuclide ventriculography at rest and exercise
      in patients with acute MI treated with thrombolysis or primary angioplasty.
      METHODS: A total of 272 consecutive patients with acute MI who were randomized to
      thrombolysis or primary coronary angioplasty underwent predischarge resting and
      exercise radionuclide ventriculography. Left ventricular ejection fraction at
      rest, decrease in ejection fraction during exercise > 5 units below the resting
      value, angina pectoris, ST-segment depression, and exercise test ineligibility
      were related to subsequent cardiac events (cardiac death, nonfatal reinfarction)
      during follow-up. RESULTS: During a mean follow-up of 30 +/- 10 months, cardiac
      death occurred in 11 (4%) patients and nonfatal reinfarction in 14 (5%) patients.
      Resting left ventricular ejection fraction was the major risk factor for cardiac
      death. In patients with an ejection fraction < 40%, cardiac death occurred in 16%
      compared with 2% in those with an ejection fraction > or = 40% (p = 0.0004). In
      addition, cardiac death tended to be higher in patients ineligible than in those
      eligible for exercise testing (11 vs. 3%, p = 0.08). None of the other exercise
      variables (decrease in ejection fraction during exercise > 5 units below the
      resting value, angina pectoris or ST-segment depression) were predictive for
      cardiac death. When all exercise test variables in each patient were combined and
      expressed as a risk score, a low risk (n = 185) and a higher risk (n = 87) group
      of patients could be identified, with cardiac death occurring in 1 and 10%,
      respectively. As the predictive accuracy of a negative test was high,
      radionuclide ventriculography was of particular value in identifying patients at
      low risk for cardiac death. Radionuclide ventriculography was not able to predict
      recurrent nonfatal MI. CONCLUSION: In patients with MI treated with thrombolysis
      or primary angioplasty, radionuclide ventriculography may be helpful in
      identifying patients at low risk for subsequent cardiac death. In this respect,
      left ventricular ejection fraction at rest was the major determinant. Variables
      reflecting residual myocardial ischemia were of limited prognostic value.
      Identification of a large number of patients at low risk allows selective use of
      medical resources during follow-up in this subgroup and has significant
      implications for the cost effectiveness of reperfusion therapies.

PMID- 9562936
TI  - Patterns of angiotensin-converting enzyme inhibitor prescriptions, educational
      interventions, and outcomes among hospitalized patients with heart failure.
AB  - BACKGROUND: Among hospitalized patients with heart failure, we describe
      characteristics associated with prescription of angiotensin-converting enzyme
      (ACE) inhibitors in the doses recommended by clinical practice guidelines. We
      also describe the impact of ACE inhibitor prescriptions, increases in ACE
      inhibitor dose, and nonpharmacologic educational interventions on readmission
      free survival rates. HYPOTHESIS: We hypothesize that care by a cardiologist
      physician and higher mean arterial blood pressure on admission are associated
      with receipt of optimal ACE inhibitor doses. We hypothesize that receipt of an
      ACE inhibitor at discharge and an increase in ACE inhibitor dose during
      hospitalization are associated with superior readmission-free survival. METHODS:
      Between January 1, 1992, and December 31, 1993, medical records were reviewed for
      consecutively hospitalized patients with a principal diagnosis of heart failure
      at an academic medical center. Documented instructions and medications prescribed
      at discharge were abstracted. Deaths and readmissions through December 31, 1994,
      were identified with the National Death Index and the study institution's
      administrative data base, respectively. RESULTS: During 1992 and 1993, 387
      patients were discharged alive from hospitalization for heart failure. Among
      patients discharged on enalapril or captopril, 18% received doses recommended by
      heart failure clinical practice guidelines. Patients discharged on a recommended
      ACE inhibitor dose were more likely to be African-American and had lower sodium
      levels and higher mean arterial pressures than patients discharged on lower ACE
      inhibitor doses. In survival analyses, an increase in ACE inhibitor dose was
      associated with improved readmission-free survival, independent of left
      ventricular systolic function type. Receipt of an ACE inhibitor at discharge was
      also associated with superior readmission-free survival, while nonpharmacologic
      educational instructions were not associated with improved outcomes. CONCLUSION:
      Interventions are needed to improve the frequency with which ACE inhibitors are
      prescribed at recommended doses to hospitalized patients with heart failure. We
      conclude that among these patients, receipt of an ACE inhibitor at discharge and
      an increase in ACE inhibitor dose during hospitalization are each associated with
      measurable effects on readmission-free survival, while provision of educational
      instructions as currently practiced is not associated with better outcomes.

PMID- 9562937
TI  - Circadian rhythm of autonomic activity in patients with obstructive sleep apnea
      syndrome.
AB  - BACKGROUND AND HYPOTHESIS: Although the immediate effects of sleep apnea on
      hemodynamics and the neurological system have been studied, little is known about
      the circadian rhythm of heart rate variability in patients with obstructive sleep
      apnea syndrome (OSAS). The purpose of the present study was to investigate the
      effects of sleep apnea on the autonomic activity during daytime, which may play
      some role in the pathogenesis of cardiovascular complications in OSAS. METHODS:
      We studied 18 middle-aged male patients with OSAS and 10 age-matched control
      subjects. Patients with OSAS were classified according to the severity of OSAS:
      patients with an apnea index (AI) < 20 were considered to have mild OSAS (Group
      1, n = 8) and patients with an AI > or = 20 were considered to have severe OSAS
      (Group 2, n = 10). Heart rate variability was calculated from the 24-h ambulatory
      electrocardiograms by the Fourier transformation. Power spectra were quantified
      at 0.04-0.15 Hz [low frequency power (LF)ln(ms2)] and 0.15-0.40 Hz [high
      frequency power (HF)ln(ms2)]. The HF component and the ratio of LF to HF were
      used as indices of the parasympathetic and sympathetic activity, respectively.
      RESULTS: The circadian rhythms of the LF, HF, and LF/HF ratio differed
      significantly in Group 2 compared with Group 1 and control subjects (p < 0.05).
      Hypertension (> 160/95 mm Hg) was found in 7 (70.0%) of 10 patients in Group 2,
      and in 1 (12.5%) of 8 patients in Group 1. Echocardiographic evidence of left
      ventricular hypertrophy (LVH) (an interventricular septal thickness or a left
      ventricular posterior wall thickness > or = 12 mm) was found in 3 (30.0%) of 10
      patients in Group 2, and in 1 (12.5%) of 8 patients in Group 1. The mean HF from
      4 A.M. to 12 noon was significantly lower in Group 2 than in Group 1 and the
      control group, and it correlated significantly with the lowest nocturnal SaO2 (r
      = 0.58, p < 0.05). The mean LF/HF ratio during the same period was significantly
      higher in Group 2 than in Group 1 and the control group, and it correlated
      significantly with total time of the nocturnal oxygen saturation < 90% (r = 0.64,
      p < 0.005) and the lowest nocturnal SaO2 (r = 0.56, p < 0.05). Ventricular
      tachycardia was found in the early morning in one patient, ST-T depression in two
      patients, and sinus arrest in two patients in Group 2. CONCLUSION: These findings
      suggest that sleep-disordered breathing associated with severe oxygen
      desaturation might influence heart rate variability not only during sleep but
      also during daytime. OSAS per se might contribute to altered circadian rhythm in
      autonomic activity leading to the development of cardiovascular diseases.

PMID- 9562938
TI  - Influence of tissue affinity of angiotensin-converting enzyme inhibitors on left
      ventricular remodeling after myocardial infarction.
AB  - BACKGROUND: The demonstration of local renin-angiotension systems has raised the
      question of whether angiotensin-converting enzyme (ACE) inhibitors with different
      tissue affinities differ with regard to their effects on postinfarction
      remodeling. HYPOTHESIS: The study was undertaken to investigate the influence of
      ACE inhibitors with different tissue affinity on morphology and function of the
      infarcted left ventricle. METHODS: In all, 52 patients (17 women, 35 men, 38-73
      years) with large acute myocardial infarction were randomized to receive either
      25-75 mg/day captopril or 10-20 mg/day fosinopril beginning on the Day 7 after
      infarction. Of these, 28 had anterior and 24 had posterior wall infarctions.
      Infarct size was determined by the creatine kinase integral method. Fifty
      patients were examined by cinemagnetic resonance imaging (CMRI) 1 and 26 weeks
      after infarction. The following parameters were determined: left ventricular end
      diastolic and end-systolic volume index (LVEDVI, LVESVI), ejection fraction
      (LVEF), infarct weight, and muscle mass (LVMM). The volume-to-mass ratio (VMR)
      was calculated and the clinical status according to the guidelines of the New
      York Heart Association (NYHA) was documented at each examination time. The
      results were compared with those of a historical sample without ACE-inhibitor
      therapy examined in an identical manner (n = 31, 10 women, 21 men, 36-75 years).
      RESULTS: LVEDVI and LVESVI increased in the first 6 months after infarction by
      24.9 and 36.6%, respectively, in the historical sample; by 11.0 and 7.8%,
      respectively, under captopril; and by 13.1 and 10.7%, respectively, under
      fosinopril. LVEF decreased by 14.9% in the untreated sample, by 3.7% under
      captopril and by 5.0% under fosinopril. Infarct weight and LVMM increased by 12.7
      and 15.3%, respectively, without ACE inhibition, by 5.7 and 10.1%, respectively,
      in patients treated with captopril, and by 6.1 and 9.3%, respectively, in
      patients treated with fosinopril. The VMR increased by 7.4% in the historical
      sample, by 3.5% in the captopril group, and by 1.8% in the fosinopril group. The
      NYHA clinical status improved by 18.2% without ACE inhibition, by 42.9% in the
      captopril group, and by 26.3% in the fosinopril group. The differences between
      the two ACE-inhibitor groups and the reference group were all significant, while
      the differences between the captopril group and the fosinopril group were
      significant only for VMR (p < 0.01) and NYHA class (p < 0.05). CONCLUSIONS: Both
      captopril and fosinopril have a comparable positive influence on postinfarction
      remodeling and on clinical status. Lipophilicity and tissue affinity do not seem
      to play a clinically important role in ACE-inhibitor therapy after infarction.

PMID- 9562939
TI  - Long-term outcome of spinal cord electrical stimulation in patients with
      refractory chest pain.
AB  - BACKGROUND AND HYPOTHESIS: Treatment of patients with refractory chest pain
      remains a challenge. In this study, the long-term clinical effects of spinal cord
      electrical stimulation were evaluated in 10 consecutive male patients (mean age
      53.7 years) with chronic chest pain in a prospective observational study.
      METHODS: After placement of the electrode in an epidural position and before
      implantation of the device, patients were subjected to clinical evaluation,
      including atrial pacing, in order to document significant antianginal effects.
      RESULTS: Spinal cord electrical stimulation abolished or improved pacing time to
      angina by more than 50% in seven of the patients who subsequently had the device
      implanted. In three of these patients, the system was ineffective after a period
      of 3-9 months despite paresthesia in the area of anginal pain with electrical
      stimulation. The effects of treatment remained satisfactory in the remaining
      patients (40%) after a mean follow-up of 60 (45-72) months. Thus, a long-lasting
      clinical response was able to be predicted in 57% of the patients. CONCLUSION:
      Spinal cord electrical stimulation is one of the few therapeutic options in
      inoperable patients with refractory chest pain.

PMID- 9562940
TI  - Comments about the electrocardiographic signs of right ventricular infarction.
AB  - This manuscript was written in an effort to emphasize the points made by Porter
      et al. (Clin Cardiol 1997; 20:971-973). Right ventricular infarction may be
      erroneously interpreted as an anteroseptal infarction because of elevation of the
      S-T segments in leads V1-V4. The two can be separated when, using the Grant
      method of analysis, the S-T segments are represented as vectors: the mean S-T
      vector is directed inferiorly, to the right, and anteriorly when there is an
      inferior-right ventricular infarct, and superiorly, to the left, and anteriorly
      when there is an anteroseptal infarction. Other aspects of right ventricular
      infarction are also discussed.

PMID- 9562941
TI  - Hemangioma of the heart.

PMID- 9562942
TI  - Severe transmural myocardial ischemia after dipyridamole administration
      implicating coronary steal.
AB  - Myocardial perfusion imaging with coronary vasodilators is routinely used for
      patients with suspected coronary disease who are unable to exercise. Since these
      agents work by increasing blood flow without significantly changing myocardial
      oxygen demand, they generally do not produce ischemia. A minority of patients
      show evidence of ischemia which some investigators suggest is due to a coronary
      steal phenomenon, but this has been challenged by several investigators. We
      present the case of a patient who developed severe transmural myocardial ischemia
      manifested by ST-segment elevation and severe perfusion defects which occurred
      after dipyridamole administration and which were reversed with aminophylline and
      nitroglycerin. This case supports the notion that coronary vasodilation with
      dipyridamole can induce a coronary steal.

PMID- 9562943
TI  - Dextrocardia and corrected transposition of the great arteries (I,D,D) in a case
      of Kartagener's syndrome: a unique association.
AB  - Kartagener's syndrome (KS) usually includes mirror-image dextrocardia. The
      incidence of congenital heart disease in KS is comparable with that in the
      general population. This paper reports on a case of Kartagener's syndrome
      associated with dextrocardia, corrected transposition of the great arteries
      (I,D,D), ventricular septal defect, and valvar pulmonary stenosis in an 8-year
      old girl.

PMID- 9562944
TI  - Cerebral infarction in a patient with congenital complete heart block.
AB  - Stokes-Adams attacks are fairly common in children with congenital complete heart
      block, but the occurrence of cerebral infarction is quite unusual. We present the
      case of a 13-year-old boy with congenital heart block and an embolic stroke
      involving the cerebral artery. Echocardiography revealed no valvular
      regurgitation, hypokinetic segments, mural thrombus, or myxoma.
      Electrocardiographic monitoring demonstrated good response of ventricular rate to
      exercise and no episodes of atrial or ventricular dysrhythmia. It is assumed that
      embolism occurred due to bradycardia.

PMID- 9562945
TI  - Ticlopidine-induced neutropenia mimicking sepsis early after intracoronary stent
      placement.
AB  - We report a case of ticlopidine-induced profound neutropenia early in the course
      of therapy, which was manifest as a febrile systemic illness mimicking sepsis.
      This clinical presentation was potentially indicative of a contaminated
      intracoronary stent. The patient's signs and symptoms of illness promptly
      resolved with removal of ticlopidine, and no infection was documented. Review of
      indications for ticlopidine use, potential adverse effects, and monitoring
      recommendations are discussed.

PMID- 9562946
TI  - James Wardrop.

PMID- 9562947
TI  - [Prognostic value of dipyridamole echocardiography in 1st acute uncomplicated
      myocardial infarction].
AB  - BACKGROUND: To assess the prognostic value of dipyridamole stress
      echocardiography in survivors of a first uncomplicated acute myocardial
      infarction. PATIENTS AND METHODS: A total of 75 patients (68 men, 7 women) aged
      58 years (range, 37-77) were studied 3-5 days after a first acute myocardial
      infarction and followed up for a mean of 10 months. Dipyridamole infusion was
      administered at high doses: 0.56 mg/kg, adding 0.28 mg/kg if the test was still
      negative. Two-dimensional echocardiography was continuously recorded during
      infusion and the test was considered positive if a decrease in regional
      contractile function appeared and negative if no assynergy was observed up to 15
      min after the beginning of dipyridamole administration. A wall motion score index
      of regional function was derived by summation of individual segment scores
      divided by the number of interpreted segments. This was calculated for rest and
      peak dipyridamole echocardiograms. Fifty of 75 patients underwent coronary
      angiography based on clinical criteria. RESULTS: There were 31 coronary events: 4
      deaths, one reinfarction, 13 angina. Thirteen patients underwent coronary
      revascularization (9 bypass and 4 angioplasty). Dipyridamole echocardiography was
      positive in 29 patients (39%) and negative in 46 patients (61%). Twenty patients
      (69%) presented coronary events in the group of positive test versus only 11
      (24%) of negatives (p = 0.0001). Four patients died in the positive group while
      none in the negative group. Sensitivity, specificity and accuracy for all cardiac
      events were 65, 80 and 73%, respectively. Significant variables from univariate
      analysis were dipyridamole stress echocardiography response, wall motion score
      index at peak dipyridamole, ischemic changes in ECG and treatment with two or
      more antianginal drugs. Multivariate analysis showed positive dipyridamole
      echocardiography as the only independent prognostic factor to predict cardiac
      events in postmyocardial infarction patients (RR = 2.56; 95% CI = 1.12-5.84).
      Four of 19 patients with one vessel disease and 17 of 22 patients with 2-3 vessel
      disease presented a positive dipyridamole test; whereas the test was negative in
      the remaining nine patients with normal coronary angiography. CONCLUSION:
      Dipyridamole stress echocardiography is a safe and feasible pharmacologic stress
      imaging method to stratify postmyocardial infarction patients at risk of
      cardiovascular events.

PMID- 9562948
TI  - [Use of antihypertensive drugs in Spain, 1985-1995].
AB  - BACKGROUND: This study has analysed the trend of antihypertensive drugs
      consumption in Spain from 1985 to 1995, its economical impact and the correlation
      with the available scientific evidence. The utilization of calcium channel
      blockers in the context of the recent controversial about their safety profile
      was also evaluated. METHODS: Drugs from the ATC groups C02, C03 (excluding C03C),
      C07, C08 (excluding nimodipine and nicardipine) and C09 were included (ATC
      classification, 1996 version). Drug utilization data and cost figures were
      obtained from the databases ECOM and FAR-90 of the Ministry of Health. These
      databases contain the number of packages sold in community pharmacies that are
      charged to the National Health System. Data are expressed in defined daily doses
      per 1,000 inhabitants per day (DHD). The cost is expressed in current and
      constant pesetas. RESULTS: The use of antihypertensives increased from 34.78 DHD
      in 1985 to 103.55 DHD in 1995. Angiotensin-converting enzyme inhibitors (ACEI)
      and calcium channel blockers (CCB) are responsible for 89% of the total increase.
      Thiazides and beta-blockers showed a mild increase, although its relative
      contribution to the total figures declined from 72 to 32% at the end of the
      period. Rauwolfia alcaloids and antiadrenergic drugs sales were negligible (0.4%
      of total sales in 1995). Within the thiazides, consumption was concentrated in
      products containing > or = 50 mg hydrochlorothiazide or equivalent. Enalapril,
      captopril, nifedipine and the fixed-dose association of hydrochlorothiazide with
      amiloride were the most widely used drugs. The cost of antihypertensive drugs in
      current pesetas raised eight times through the study period reaching 105,501
      millions pesetas in 1995; 89% of the cost corresponded to ACEI and CCB. Expressed
      in constant pesetas the cost increase was four fold. The recent controversia
      about CCB did not have influence on its consumption. CONCLUSIONS: The pattern of
      use of antihypertensive drugs in Spain does not follow the available scientific
      evidence. Drugs with less documented effectiveness are the most prescribed; even
      considering the same effectiveness, efficiency is lower for drugs with higher
      utilization rates. The available presentations for thiazides makes their
      utilization in the optimal dosification difficult.

PMID- 9562949
TI  - [Factors that determine intensity of response to treatment with tiludronate in
      Paget's disease].
AB  - OBJECTIVE: To investigate the influence of both clinical and pharmacokinetic
      factors as determinants of response to tiludronate in Paget's bone disease (PBD).
      PATIENTS AND METHODS: Twenty six PBD patients with serum alkaline phosphatase
      (SAP) levels at least twice the normal upper limit were enrolled. The sample
      included 17 (65%) men and 9 (35%) women whose mean age (SD) was 60.3 (9.8)
      (range: 38-76). Each patient received 400 mg/day of tiludronate, per os, for 90
      (6) days. The SAP variations were considered as the main parameter of response.
      Plasma concentrations of tiludronate were assayed using the HPLC method with UV
      detection; the maximum and minimum (Cmin) concentration, as well as the area
      under a concentration-time curve were calculated. Multivariate regression
      analysis was performed to assess the influence on tiludronate effect. RESULTS:
      Mean (SD) percent reduction of SAP from the initial values ranged from 30.5
      (13.9) at the end of the first month of drug intake to a nadir of 76.1 (8.8)
      achieved 6 months after the treatment was stopped. Serum SAP activity fell to
      normal range in 7 (27%) patients at the end of the therapy period, in 17 (65%)
      three months later, and in 18 (69%) one year thereafter. One year after the
      treatment ended only one patient had evidence of relapse. Final multivariate
      regression model showed that the percent reduction of SAP increases by 11.9
      percent points per Cmin tiludronate unit and by 0.006 points per basal SAP unit,
      and decreases by 0.52 per year of age. Out of 13 patients with bone pain, 9 (69%)
      experienced relief within the second and third months of treatment. No clinical
      or laboratory severe side effects were seen and only five patients (19%) had mild
      adverse events. CONCLUSIONS: These results confirm that tiludronate leads to a
      marked suppression of PDB clinical and biochemical activity. Cmin of tiludronate
      in plasma is the best predictor of biochemical response.

PMID- 9562950
TI  - [Treatment of arterial hypertension. Among all of us, we do not do it too bad at
      all].

PMID- 9562951
TI  - [Surgery in epilepsy: time for reflection].

PMID- 9562952
TI  - [Health plan of the Ministry of Health and Demand].

PMID- 9562953
TI  - [Prevalence of antibodies to Entamoeba histolytica in the Northern area of the
      Province of Huelva].

PMID- 9562954
TI  - [Electronic references].

PMID- 9562955
TI  - [Upper dysphagia as an onset form of Paget's disease of bone resolved with
      medical treatment].

PMID- 9562956
TI  - [Significance of carcinoembryonic antigen in the follow up of colorectal cancer].

PMID- 9562957
TI  - [Use of angiotensin-converting enzyme inhibitors in patients with congestive
      heart failure. Same efficacy? Same costs?].

PMID- 9562958
TI  - [Treatment of palmar hyperhidrosis by video-thoracoscopic thoracic
      sympathectomy].

PMID- 9562959
TI  - [Hairy leukoplakia in immunodeficiency not due to HIV].

PMID- 9562960
TI  - Molecular genetic, biochemical, and clinical implications of gonadotropin
      receptor mutations.
AB  - Human reproductive function is regulated mainly by luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH). Mutations of the human LH/ chorionic
      gonadotropin receptor (LHR) and the FSH receptor (FSHR) leading to either
      constitutive activation or inactivation of the receptors have been identified.
      All activating mutations of the LHR and the FSHR are located within the exon
      encoding the transmembrane domain while the inactivating mutations are scattered
      throughout the coding sequence. A number of activating and inactivating mutations
      of the LHR have been found while only one activating and three inactivating
      mutations of the FSHR are known. Activating mutations of the LHR cause familial
      male-limited precocious puberty (FMPP) while that of the FSHR has been shown to
      restore the reproductive capability of a hypophysectomized male. Inactivating
      mutations of the LHR cause Leydig cell hypoplasia (LCH) in males while that of
      the FSHR causes hereditary hypergonadotropic ovarian dysgenesis (ODG) in females.
      Activating mutations of both receptors are dominant while inactivating mutations
      are recessive. Genotype-phenotype correlation is best established for the
      inactivating mutations of LHR. Severity of clinical phenotype in LCH correlates
      with the amount of residual activity of the mutated LHR. Comparison of the
      clinical impact of the activating and the inactivating mutations of the receptors
      indicates that male reproductive capacity depends primarily on LH while female
      reproductive capacity depends primarily on FSH.

PMID- 9562961
TI  - Detection of intrauterine viral infection using the polymerase chain reaction.
AB  - Intrauterine viral infection commonly presents as nonimmune hydrops fetalis or
      intrauterine growth restriction. Cytomegalovirus (CMV) and parvovirus are
      commonly recognized causes of fetal infection using serology and cultures. We
      used the polymerase chain reaction (PCR) to evaluate the frequency of fetal viral
      infection and the associated clinical course and outcome. Specimens (amniotic
      fluid, fetal blood, pleural fluid, tissue) from 303 abnormal pregnancies at risk
      for viral infection and 154 controls were analyzed using primers for CMV, herpes
      simplex virus, parvovirus B19, adenovirus, enterovirus, Epstein-Barr virus, and
      respiratory syncytial virus. Viral genome was detected in 144/371 samples (39%)
      or 124/303 patients (41%), with adenovirus (n = 74 patients; 24%), CMV (n = 30
      patients; 10%), and enterovirus (n = 22 patients; 7%) most common. Only 4/154
      (2.6%), unaffected control patients' samples were PCR positive. We conclude that
      diagnosis of fetal viral infection by PCR is common in abnormal pregnancies.
      Adenovirus and enterovirus may cause fetal infection that have been previously
      unrecognized.

PMID- 9562962
TI  - Use of a reverse transcriptase-polymerase chain reaction assay to analyze allele
      specific expression in individual hippocampal neurons.
AB  - We report here a single-cell RT-PCR assay for allele-specific gene expression
      that can be used to probe for somatic variability within the CNS. Such
      variability, arising from epigenetic (nonmutational) events or somatic mutation
      early in development, may give clues as to clonal origin and may also affect the
      inheritance pattern of some CNS disorders. As a model system, we used reciprocal
      F1 hybrids of the cross Mus musculus C57BL/6J x Mus musculus castaneus. RNA was
      isolated from individual dissociated pyramidal neurons from hippocampi of F1
      pups. For each gene of interest, single base polymorphisms were identified
      between the two parental strains by automated sequencing of RT-PCR products.
      Allele-specific expression was then analyzed by means of the previously described
      quantitative RT-PCR single nucleotide primer extension (SNuPE) assay (Singer-Sam
      et al., PCR Methods Appl. 1:160-163, 1992). Individual neurons showed monoallelic
      expression of the two control genes, X-linked Rps4, and the imprinted gene Snrpn;
      in contrast expression of Ncam and F3cam, coding for neural cell adhesion
      molecules, was found to be biallelic.

PMID- 9562963
TI  - Gene therapy with p53 and a fragment of thrombospondin I inhibits human breast
      cancer in vivo.
AB  - We recently reported that a p53 encoding plasmid (BAP-p53) complexed to liposomes
      administered intravenously markedly attenuates the growth of a malignant human
      breast tumor. We now have found that systemically delivered liposomes complexed
      to a plasmid expressing an established antiangiogenic peptide of thrombospondin I
      (BAP-TSPf) decreased the growth of MDA-MB-435 tumors compared to controls in nude
      mice. Compared to BAP-p53, the BAP-TSPf group had a similar antitumor efficacy.
      More importantly, liposomes complexed with BAP-TSPf and BAP-p53 synergistically
      decreased the growth of MDA-MB-435 tumors when compared to either BAP-p53 or BAP
      TSPf alone. Furthermore, we also determined that the combination therapy of p53
      and TSPf inhibited endothelial cells in vitro more than either p53 or TSPf alone.
      There was also a significant decrease of the blood vessel density in the
      combination p53 and TSPf treatment group compared to the control groups. These
      results suggest that liposomes complexed to a tumor suppressor and antiangiogenic
      genes may be effective in treating metastatic tumors.

PMID- 9562964
TI  - A novel mutation identified in carnitine palmitoyltransferase II deficiency.
AB  - Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive
      disorder of mitochondrial fatty-acid oxidation which presents as three distinct
      phenotypes (neonatal, infantile, and adult onset). CPT II exons from an adult
      onset CPT II-deficient patient were amplified and directly sequenced to further
      investigate the molecular basis of this disorder. A novel mutation, C471T, in
      exon 4 of the carnitine palmitoyltransferase II gene was found which created a
      stop codon, TGA, at residue 124 of the protein (R124Stop). This mutation would
      result in severe protein truncation. This unique mutation was found on one allele
      while the S113L mutation, previously reported, was present on the other allele.

PMID- 9562965
TI  - Synthetic mimics of surfactant proteins B and C: in vitro surface activity and
      effects on lung compliance in two animal models of surfactant deficiency.
AB  - Synthetic surfactant peptides SP-B1-78 and SP-C1-31 in a standard phospholipid
      mixture have been employed to examine the correlation between in vitro surface
      activity and in vivo function of synthetic surfactant preparations in the
      isolated rat lung and premature rabbit models of respiratory distress syndrome.
      Monolayer techniques showed that SP-B peptides have a high propensity for
      association with a phospholipid structure. By dynamic respreading, synthetic SP-B
      and SP-C showed rapid spreading and attained low surface tensions. Used as
      replacement surfactants in two animal models, these synthetic surfactant
      preparations partially restored lung compliance in lavaged rats and premature
      rabbits better than a pure phospholipid preparation and to a degree comparable to
      clinical surfactant, measured by pressure/volume curves. Our data confirm that in
      vitro functional determinations of synthetic surfactant peptides are instrumental
      in the preparation of replacement surfactants, and that dispersions thus selected
      represent viable therapeutic alternatives to current treatments for respiratory
      distress syndrome.

PMID- 9562966
TI  - Mechanisms of insulin-resistant glucose utilization in rat skeletal muscle.
AB  - Defects in glucose uptake are among the primary defects associated with
      peripheral insulin resistance, but fundamental mechanisms leading to this state
      are poorly understood. In order to elucidate mechanisms leading toward defects in
      glucose transport, we have used a partially pancreatectomized infusion (PxI)
      animal model with infusions of saline, glucose, or insulin to examine individual
      and combined effects of hyperglycemia and hyperinsulinemia on skeletal muscle
      glucose utilization. Moderate hyperglycemia induced by pancreatectomy reduced
      basal hindlimb muscle glucose utilization by 57% without affecting maximal
      insulin-stimulated glucose utilization; insulin administered in an amount
      sufficient to correct this hyperglycemia did not alter basal glucose utilization,
      but maximal insulin-stimulated glucose utilization was sharply diminished (75%);
      hyperglycemia with hyperinsulinemia similarly reduced basal and maximal insulin
      stimulated glucose utilization. In order to establish the role of the glucose
      transporter protein in these insulin-resistant states, we quantified GLUT 4
      content by immunoblotting and GLUT 4 mRNA by solution hybridization/RNAse
      protection assays. Hyperglycemia (2 weeks) reduced total muscle GLUT 4 protein
      content (53%) and mRNA (46%), while subsequent hyperinsulinemia (72 h) with
      either normo- or hyperglycemia partially restored both total GLUT 4 protein and
      mRNA levels. As insulin-stimulated GLUT 4 content in plasma membranes was not
      diminished by combined hyperglycemia/hyperinsulinemia, these results indicate
      functional GLUT 4 translocation in this model and suggest suppression of GLUT 4
      transporter activity.

PMID- 9562967
TI  - Insulin sensitivity indices calculated from basal and OGTT-induced insulin,
      glucose, and FFA levels.
AB  - Insulin Sensitivity Indices for glycemia [ISI(gly)] and blood FFA [ISI(ffa)] can
      be calculated with the formulas: ISI(gly) = 2/[(INSp x GLYp) + 1], and ISI(ffa) =
      2/[(INSp x FFAp) + 1], where INSp, GLYp and FFAp = insulinemic, glycemic, and FFA
      areas during OGTT (75 g glucose) of the person under study, simplified by
      considering only data at 0 and 2 h (0-2 h areas), according to WHO criteria or,
      better, at 0, 1 and 2 h (0-1-2 h areas). Expressed as unit/ volume.h-1, 0-1-2 h
      area is equal to 1/2 value at 0 min + value at 1 h + 1/2 value at 2 h, while 0-2
      h area is equal to value at 0 + value at 2 h. Instead of areas, basal levels can
      also be used. Basal levels and areas are expressed taking the mean normal value
      as unit, so that in normal subjects ISI(gly) and ISI(ffa) are always around 1,
      with maximal variations between 0 and 2. Each laboratory should have its normal
      reference values for basal levels and OGTT areas. However, reliable mean normal
      values were selected from literature. Based on meta-analysis of published data,
      ISI(gly) and ISI(ffa) were reduced in subjects who were overweight and/or IGT and
      in NIDDM patients and their relatives. Moreover, correlation of ISI(gly) with the
      euglycemic clamp data was significant. However, it should be stressed that the
      clamp procedure is performed under artificially induced steady-state whereas
      ISI(gly) and ISI(ffa) are obtained under rather physiological conditions, with
      hormonal and metabolic variables unmodified, thus being suitable to assess whole
      body insulin sensitivity in the clinical setting.

PMID- 9562968
TI  - Glutamate triggers cell death specifically in mature central neurons through a
      necrotic process.
AB  - Whereas immature neurons have been shown to be sensitive to hypoxia and to
      develop apoptosis, the role of glutamate in neuronal injury is more
      controversial. Effects of a 6-h exposure to glutamate or its analogues (100
      microM) were studied over a period of 72 h in cultured central neurons at two
      maturational stages, i.e., after 6 and 13 days in vitro. Glutamate was without
      toxic effects in 6-day-old neurons which became vulnerable to the excitatory
      amino acid when they were coexposed to 30 nM staurosporine, a protein kinase C
      inhibitor. In 13-day-old neurons, glutamate and derivatives led to cell death and
      altered functional activity of surviving neurons over the next 72 h, the greatest
      injury being observed with glutamate and NMDA. At this developmental stage,
      persistent inhibition of protein synthesis induced by glutamate, as well as lack
      of beneficial effect from cycloheximide, argues against programmed neuronal
      death. Accordingly, quantitative cell nuclear analysis using a fluorescent dye
      revealed that the effects of glutamate reflect necrosis but not apoptosis.
      Furthermore, the inability of immature neurons to inhibit protein kinase C may
      account for their higher resistance to excitotoxicity.

PMID- 9562969
TI  - Mild hyperphenylalaninemia and heterozygosity of the phenylalanine hydroxylase
      gene.
AB  - Newborn screening for phenylketonuria (PKU) is now the standard of practice.
      Initial phenylalanine blood levels of 240 mumol/L result in referral of affected
      newborns to medical facilities experienced in caring for patients with metabolic
      disorders. This case report concerns a female infant born in 1976 with a
      presumptive positive PKU screening test on the third day of life of 240 mumol/L
      phenylalanine. Follow-up levels while the mother was breast feeding on the sixth
      day of life were 324 and, on the 27th day, 312 mumol/L. She was subsequently lost
      to follow-up at age 11 years, but returned at 19 years of age due to pregnancy,
      with a blood phenylalanine level of 132 mumol/L. Mutation studies then were
      performed documenting that she was a carrier for the phenylalanine hydroxylase
      gene and did not have hyperphenylalaninemia. The mother's parents and the infant
      were also genotyped confirming heterozygosity. The infant on follow-up is
      completely normal, following a normal pregnancy.

PMID- 9562970
TI  - 11q13 allelotype analysis in 27 northern American MEN1 kindreds identifies two
      distinct founder chromosomes.
AB  - We analyzed constitutional and tumor DNA from 27 MEN1 kindreds not known to be
      related to each other. Disease allele haplotypes were constructed for each
      pedigree based on shared alleles from two or more affected members and from
      determination of allelic loss patterns in their tumors. Analysis of disease
      allele haplotypes showed unexpected linkage disequilibrium at marker PYGM.
      Further haplotype analysis indicated this could be explained by the presence of
      two founder chromosomes, one in four families, the other in three. A shared
      disease haplotype was not observed among two MEN1 kindreds with the prolactinoma
      phenotype of MEN1.

PMID- 9562971
TI  - McLaughlin Research Institute.

PMID- 9562972
TI  - HIV-1 nuclear import: matrix protein is back on center stage, this time together
      with Vpr.

PMID- 9562973
TI  - Proteasome inhibitors prevent the degradation of familial Alzheimer's disease
      linked presenilin 1 and potentiate A beta 42 recovery from human cells.
AB  - BACKGROUND: Several lines of evidence suggest that most of the early-onset forms
      of familial Alzheimer's disease (FAD) are due to inherited mutations borne by a
      chromosome 14-encoded protein, presenilin 1 (PS1). This is likely related to an
      increased production of amyloid beta-peptide (A beta) 42, one of the main
      components of the extracellular deposits called senile plaques that invade human
      cortical areas during the disease. MATERIALS AND METHODS: We set up stably
      transfected HEK293 cells overexpressing wild-type (wt) and various FAD-linked
      mutated PS1. By Western blot analysis, we examined the influence of specific
      proteasome inhibitors on PS1-like immunoreactivities. Furthermore, by means of
      metabolic labeling and immunoprecipitation with A beta 40 and A beta 42-directed
      specific antibodies, we assessed the effect of the inhibitors on the production
      of A beta s by wt and mutated PS1-expressing cells transiently transfected with
      beta APP751. RESULTS: We show that two distinct proteasome inhibitors, Z-IE (Ot
      Bu)A-Leucinal and lactacystin, increase in a time- and dose-dependent manner the
      immunoreactivities of both wt and mutated PS1. Furthermore, we demonstrate that
      PS1 is polyubiquitinated in these cells. Other inhibitors, ineffective on the
      proteasome, fail to protect wt and mutated PS1-like immunoreactivities. We also
      establish that the FAD-linked mutations of PS1 trigger a selective increased
      formation of A beta 42 as reflected by higher A beta 42 over total A beta ratios
      when compared with wtPS1-expressing cells. Interestingly, this augmentation was
      further amplified by proteasome inhibitors in cells expressing mutated but not
      wtPS1. CONCLUSION: Altogether, our data indicate that PS1 undergoes
      polyubiquitination in HEK293 cells and that the proteasome contributes to the
      degradation of wt and FAD-linked PS1, thereby directly influencing the A beta
      production in human cells.

PMID- 9562974
TI  - Ratio of bcl-xshort to bcl-xlong is different in good- and poor-prognosis subsets
      of acute myeloid leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous collection of
      leukemic disorders ranging from chemotherapy-sensitive subsets [inversion 16 and
      t(8;21)], which often can be cured with cytosine arabinoside alone, to the most
      resistant subsets, which can survive even supralethal levels of combination
      alkylator chemotherapy (cytogenetic subsets monosomy 5 and monosomy 7). MATERIALS
      AND METHODS: To analyze the expression of BCL-2 family genes, which are expressed
      in these subsets of AML, we used PCR sequence amplification reactions that are
      dependent on oligonucleotide primers representing the BH1 and BH2 homology
      domains to generate the unique regions between BH1 and BH2. These primers are
      conserved among all members of the BCL-2 gene family and are separated by a 150
      nucleotide region sequence between the BH1 and BH2 domains. The PCR products
      unique to each BCL-2 family member were cloned directionally into sequencing
      vectors. The identity of the insert of each clone was determined by slotblots of
      the DNA amplified from individual colonies and by hybridization with radioactive
      probes specific to the bcl-2, bcl-x, or bax genes. RESULTS: We found that bcl-2
      is the predominant member expressed in AML samples with a poor prognosis (-5, 
      7), whereas the transcripts of bcl-x are higher than those of bcl-2 in the AML
      samples with a good prognosis [inv16, t(8;21)]. No significant difference in bax
      expression was detected between AML subsets of good and bad prognosis. The ratio
      of bcl-xlong, which inhibits apoptosis, to bcl-xshort, which promotes apoptosis,
      was determined by amplification with a pair of primers specific to bcl-x followed
      by separation of the PCR product on agarose gels. Bcl-xlong and bcl-xshort
      appeared as bands of different molecular mass on a molecular weight gel and were
      visualized by ethidium bromide staining or Southern blot analysis with a bcl-x
      specific probe. CONCLUSIONS: We found that the ratio of bcl-x long to bcl-x short
      was higher in the AML patients with a poor prognosis. These experiments showed
      that the levels of BCL-2 family members in the leukemia cells of good- and poor
      prognosis subsets are different. In addition, novel members of the BCL-2 family
      were isolated from the cells of AML patients of either prognosis.

PMID- 9562975
TI  - Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating
      mitochondrial transmembrane potential and reactive oxygen species production.
AB  - BACKGROUND: The hydrophilic bile salt ursodeoxycholate (UDCA) inhibits injury by
      hydrophobic bile acids and is used to treat cholestatic liver diseases.
      Interestingly, hepatocyte cell death from bile acid-induced toxicity occurs more
      frequently from apoptosis than from necrosis. However, both processes appear to
      involve the mitochondrial membrane permeability transition (MPT). In this study,
      we determined the inhibitory effect of UDCA on deoxycholic acid (DCA)-induced MPT
      in isolated mitochondria by measuring changes in transmembrane potential (delta
      psi m) and production of reactive oxygen species (ROS). In addition, we examined
      the expression of apoptosis-associated proteins in mitochondria isolated from
      livers of bile acid-fed animals. MATERIALS AND METHODS: Adult male rats were
      maintained on standard diet supplemented with DCA and/or UDCA for 10 days.
      Mitochondria were isolated from livers by sucrose/percoll gradient centrifugation
      and MPT was measured using spectrophotometric and fluorimetric assays. delta psi
      m and ROS generation were determined by FACScan analysis. Cytoplasmic and
      mitochondrial protein abundance were determined by Western blot analysis.
      RESULTS: DCA increased mitochondrial swelling 25-fold over controls (p < 0.001);
      UDCA reduced the swelling by > 40% (p < 0.001). Similarly, UDCA inhibited DCA
      mediated release of calcein-loaded mitochondria by 50% (p < 0.001). delta psi m
      was significantly decreased in mitochondria incubated with DCA but not with UDCA.
      delta psi m disruption was followed closely by increased superoxide anion and
      peroxides production (p < 0.01). Coincubation of mitochondria with UDCA
      significantly inhibited the changes associated with DCA (p < 0.05). In vivo, DCA
      feeding was associated with a 4.5-fold increase in mitochondria-associated Bax
      protein levels (p < 0.001); combination feeding with UDCA almost totally
      inhibited this increase (p < 0.001). CONCLUSION: UDCA significantly reduces DCA
      induced disruption of delta psi m, ROS production, and Bax protein abundance in
      mitochondria, suggesting both short- and long-term mechanisms in preventing MPT.
      The results suggest a possible role for UDCA as a therapeutic agent in the
      treatment of both hepatic and nonhepatic diseases associated with high levels of
      apoptosis.

PMID- 9562978
TI  - Molecular phylogeny of Vespidae (Hymenoptera) and the evolution of sociality in
      wasps.
AB  - The oriental Stenogastrinae is a group in which there is considerable interest as
      regards the study of evolution of sociality in wasps, because they show broad
      diversity in social behavior. Using cladistic analysis on morphological and
      behavioral data, they have been grouped together with the social Vespinae and
      Polistinae in the family of Vespidae. This is not without dispute, because
      several other morphological and behavioral characters separate Stenogastrinae
      from the other Vespidae subfamilies. DNA sequences were obtained from nuclear 28S
      ribosomal DNA and the mitochondrial 16S ribosomal DNA of two Apis species and
      nine social and three solitary wasp species of the family Vespidae. Solitary
      wasps of the family Braconidae and Pteromalidae were used as outgroups.
      Parsimony, distance, and maximum-likelihood methods of both mitochondrial and
      nuclear DNA did not support the conventional phylogenetic position of
      Stenogastrinae. In all phylogenetic reconstructions, the solitary Eumeninae were
      a sister taxon to the Polistinae + Vespinae cluster. The analyzed sequences
      provide strong evidence that sociality has independently evolved twice in the
      Vespidae.

PMID- 9562976
TI  - Inhibition of protein synthesis by nitric oxide correlates with cytostatic
      activity: nitric oxide induces phosphorylation of initiation factor eIF-2 alpha.
AB  - BACKGROUND: Nitric oxide (NO) is cytostatic for proliferating cells, inhibits
      microbial growth, and down-regulates the synthesis of specific proteins. Studies
      were undertaken to determine the mechanism by which NO inhibits total protein
      synthesis and whether the inhibition correlates with established cytostatic
      activities of NO. MATERIALS AND METHODS: In in vitro experiments, various cell
      types were exposed to NO using either donors or expression of inducible NO
      synthase (iNOS). The capacity of NO to suppress total protein synthesis, measured
      by incorporation of 35S-methionine into protein, was correlated with the capacity
      of NO to suppress cell proliferation, viral replication, or iNOS expression.
      Phosphorylation of eIF-2 alpha was examined as a possible mechanism for the
      suppressed protein synthesis by NO. RESULTS: Both NO donors and expression of the
      iNOS suppressed total protein synthesis in L929 cells and A2008 human ovarian
      tumor cells in parallel with decreased cell proliferation. Suppressed protein
      synthesis was also shown to correlate with decreased vaccinia virus proliferation
      in murine peritoneal macrophages in an iNOS-dependent manner. Furthermore, iNOS
      expression in pancreatic islets or RAW264.7 cells almost completely inhibited
      total protein synthesis, suggesting that nonspecific inhibition of protein
      synthesis may be the mechanism by which NO inhibited the synthesis of specific
      proteins such as insulin or iNOS itself. This possibility was confirmed in
      RAW264.7 cells where the inhibition of total protein synthesis correlated with
      the decreased iNOS protein. The decrease in protein levels occurred without
      changes in iNOS mRNA levels, implicating an inhibition of translation.
      Mechanistic studies revealed that iNOS expression in RAW264.7 cells resulted in
      the phosphorylation of eIF-2 alpha and inhibition of the 80S ribosomal complex
      formation. CONCLUSIONS: These results suggest that NO suppresses protein
      synthesis by stimulating the phosphorylation of eIF-2 alpha. Furthermore, our
      observations indicate that nonspecific inhibition of protein synthesis may be a
      generalized response of cells exposed to high levels of NO and that inhibition of
      protein synthesis may contribute to many of the described cytostatic actions of
      NO.

PMID- 9562977
TI  - Basic fibroblast growth factor: a missing link between collagen VII, increased
      collagenase, and squamous cell carcinoma in recessive dystrophic epidermolysis
      bullosa.
AB  - BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) have
      deficiencies of collagen type VII and have elevated levels of fibroblast
      collagenase, and a greatly increased risk of cutaneous squamous cell carcinoma.
      Patients with other genetic blistering disorders do not have elevated collagenase
      or an increased risk of squamous cell carcinoma, despite chronic wounding. The
      connection between collagen type VII deficiency, increased collagenase, and
      squamous cell carcinoma is not understood. MATERIALS AND METHODS: Urine from 81
      patients with RDEB (39 patients), junctional epidermolysis bullosa (JEB; 12
      patients), and epidermolysis bullosa simplex (EBS; 30 patients), as well as
      unaffected family members of RDEB patients (33 patients), was tested for the
      presence of basic fibroblast growth factor (bFGF) using a sensitive
      radioimmunoassay. These patients included many who were enrolled in the
      Epidermolysis Bullosa Registry and others who were referred by their physicians.
      RESULTS: Fifty-one percent of patients with RDEB had elevated levels (> 5000
      pg/g) of urinary bFGF. In contrast, none of the patients with JEB had elevated
      levels of bFGF. Twenty-one percent of clinically unaffected family members had
      elevated levels of bFGF, and 13% of patients with EBS had elevated levels of
      bFGF. The frequency of elevated bFGF values among all groups was statistically
      significant (p = 0.002), and the levels of bFGF in RDEB patients were
      significantly elevated compared with those of other groups (p < 0.05).
      CONCLUSIONS: We have found that patients with RDEB have elevated levels of bFGF,
      which may contribute to increased fibroblast collagenase and the development of
      squamous cell carcinoma. These results suggest a novel treatment for RDEB,
      namely, angiogenesis inhibitors, which may antagonize the effects of bFGF in this
      disorder. There are currently no other means of treatment for this disorder,
      which has a high morbidity and mortality rate.

PMID- 9562979
TI  - Systematics and evolution of lower Central American cichlids inferred from
      analysis of cytochrome b gene sequences.
AB  - Central American cichlids allied to the genus "Cichlasoma" are thought to be of
      South American ancestry. The group has apparently undergone extensive
      morphological, ecological, and behavioral differentiation in Central America
      following colonization. Uncertainties regarding the systematics of the group and
      the timing of colonization complicate interpretation of the biological history of
      cichlids in Central America. We determined complete cytochrome b gene sequences
      for 54 individual cichlids representing 21 species to test hypotheses regarding
      the time of origin and pattern of diversification of lower Central American
      cichlids. The data also bear on issues relating to the systematics and taxonomy
      of heroine cichlids. Our results suggest that cichlids have been in Central
      America since the middle to late Miocene. Moreover, the data provide evidence of
      a rapid radiation early in the history of the group. Similar ecomorphological
      types have evolved multiple times. Inferences of convergent morphological
      evolution may, in part, explain a lack of concordance between the mitochondrial
      gene tree and previous inferences of phylogenetic relationships based on
      observable characteristics. Phylogenetic inferences based on the molecular data
      provide support for the recognition of "sections" [erected by Regan (1905) and
      others] as distinct genera and suggest that thorough revision of Central American
      cichlids is necessary before the extent of biological diversity within the group
      can be fully appreciated.

PMID- 9562981
TI  - A clade of New World primates with distinctive alphoid satellite DNAs.
AB  - Centromerically located alphoid satellite DNAs are present in all primates. They
      typically consist of arrays of a 340-bp monomeric unit that is composed of
      related, but diverged, 170-bp subunits. A unique monomeric unit has recently been
      described: the alphoid satellite monomers of the neotropical primate Chiropotes
      satanas (bearded saki) are typically 539 bp in length. In addition, a number of
      smaller satellite sequences are present in this species. Analysis of two primates
      closely related to Chiropotes, Pithecia irrorata (saki) and Cacajao
      melanocephalus (uakari), show that they also contain unique alphoid satellites
      that are different from those of Chiropotes and different from one another.
      Southern blot and sequence analyses suggest that an alphoid satellite
      rearrangement(s) occurred early in the history of the tribe Pitheciini
      (Chiropotes, Pithecia, Cacajao) and that rearrangements are continuing to occur
      in this group of primates.

PMID- 9562980
TI  - Molecular evolution of the internal transcribed spacers (ITS1 and ITS2) and
      phylogenetic relationships among species of the family Cucurbitaceae.
AB  - Phylogenetic relationships of different members of the family Cucurbitaceae were
      estimated from sequences of the internal transcribed spacer (ITS1 and ITS2)
      regions of the nuclear ribosomal RNA genes. Twenty-six species of different
      genera belonging to different tribes and several subtribes were analyzed. The
      whole ITS regions were amplified by PCR technique and cloned, and three to five
      different clones of each species were sequenced; for some species PCR products
      were sequenced directly. ITS1 and ITS2 regions are slightly variable in length,
      with each length appearing genus-specific. A substitution rate of 3.62 x 10(-9)
      substitutions per site per year was calculated assuming 40 MYA separation time.
      Phylogenetic relationships inferred from ITS sequences of some species is in
      agreement with morphological data, but deviations to the taxonomic classification
      were also observed. A polyphyletic origin of the New World species must be
      considered. In the genus Cucurbita different "types" of ITS sequences within one
      species exist, possibly due to the high frequency of introgression during
      domestication or due to polyploidization events; in contrast, low intraspecific
      variability was detectable in the genus Cucumis, indicating different stages of
      speciation.

PMID- 9562982
TI  - Character congruence of multiple data partitions and the origin of the Hawaiian
      Drosophilidae.
AB  - We address two systematic questions, the origin and monophyly of the Hawaiian
      Drosophilidae and the question of how to analyze multiple data partitions
      containing disparate kinds of information, in this study. New evidence, from
      analysis of characters from morphology, mitochondrial DNA, and nuclear DNA
      suggests that the Hawaiian Drosophilidae are a monophyletic assemblage. Although
      we are not able to suggest a single species group which may represent the
      continental sister taxon to the Hawaiian Drosophilidae, the candidates suggested
      by our analysis, the melanicarobusta lineage and the virilis-repleta lineage,
      have been suggested by other investigators as probable sister taxa. Through
      analyses of our data partitions separately and in a variety of combinations, we
      conclude that the best phylogenetic hypothesis to be generated from multiple data
      partitions will be obtained if the data from these partitions are combined and
      analyzed simultaneously. We advocate performing tests for congruence between and
      among data partitions not to justify keeping them apart, but for understanding
      the interactions among the signals included in the analysis and how they affect
      the topology of, and support for, the total evidence tree.

PMID- 9562983
TI  - Francolin phylogenetics: molecular, morphobehavioral, and combined evidence.
AB  - The phylogenetics of francolins (Francolinus species) were reassessed by
      obtaining 660 bp of sequence of the mitochondrial DNA (mtDNA) cytochrome b gene
      from 20 species, the Common Quail Coturnix coturnix africana, and the Madagascar
      Partridge Margaroperdix madagarensis. Published sequences of the Japanese Quail
      C. c. japonica, Alectoris partridges, and the Junglefowl Gallus gallus were also
      included. Separate analysis of the 200 phylogenetically informative cytochrome b
      characters and the 25 informative morphobehavioral characters, as well as a
      combined analysis of molecular and morphobehavioral data, do not support
      francolin monophyly but provide strong evidence for two previously suggested
      clades--the quail-francolins (or partridges) and the partridge-francolins
      (pheasants/francolins). The quail-francolin clade comprises three groups of
      African francolins and three Asian species that were previously considered more
      closely related to the partridge-francolins. The partridge-francolin clade, which
      includes four groups of African francolins, forms a sister group to the Coturnix
      quails, the Madagascar Partridge, and the Alectoris partridges. The molecular
      data suggest that the two francolin clades diverged approximately 3-6 MYA.
      Climatic fluctuations of the past 2.5 MYA may have led to the diversification of
      the ecologically different francolin species groups and speciation within them.

PMID- 9562984
TI  - Paraphyletic status of Polychaeta suggested by phylogenetic analysis based on the
      amino acid sequences of elongation factor-1 alpha.
AB  - In order to judge whether or not Polychaeta is a paraphyletic group, I determined
      almost the entire amino acid sequence of elongation factor-1 alpha from thirteen
      polychaetes, two oligochaetes, two hirudineans, two vestimentiferans, and two
      molluscs. Phylogenetic analysis by the neighbor-joining (NJ) method and the
      maximum likelihood (ML) method indicated the monophyly of Clitellata (the
      oligochaetes and hirudineans). In both the NJ and ML trees, vestimentiferans and
      clitellates were derived from polychaetes independently. The present results
      strongly suggest that Polychaeta is a paraphyletic group.

PMID- 9562985
TI  - Evolution and systematics of Anopheles: insights from a molecular phylogeny of
      Australasian mosquitoes.
AB  - Relationships among the genus Anopheles and its many sibling species-groups are
      obscure despite the importance of anophelines as the vectors of human malaria.
      For the first time, the interrelationships and the origin of Australasian members
      of the subgenus Cellia are investigated by a cladistic analysis of sequence
      variation within the mitochondrial cytochrome oxidase subunit II gene. Estimated
      divergence times between many Australasian and Oriental taxa predate the mid
      Miocene collision of Australasia and Southeast Asia. Phylogenetic analysis
      suggests that two-way exchanges with Oriental mosquitoes rather than only
      immigration may have been a characteristic of anopheline paleobiogeography in
      Australasia. The Australasian fauna is mostly included in a large clade. The
      medically important Punctulatus Group is monophyletic and appears derived from
      Oriental stock. Populations within this group from as far apart as Australia and
      Vanuatu were in contact in the recent past (i.e., 0.35-2.44 mya), supporting
      dispersal rather than vicariance explanations. Some support for the monophyly of
      the Myzomyia, Neomyzomyia, and Pyretophorus Series was found. However, the
      subgenera Anopheles and Cellia and the Neocellia Series are paraphyletic, but
      branch support at these taxonomic levels was poor. The COII gene shows promise
      for questions concerning alpha taxonomy but appears to be of limited use for
      resolving deeper relationships within the Anopheles.

PMID- 9562986
TI  - A different tempo of mitochondrial DNA evolution in birds and their parasitic
      lice.
AB  - A phylogeny for the lice (Insecta: Phthiraptera: genus Dennyus) parasitic on
      swiftlets (Aves: Collocalliinae) was constructed based on mitochondrial
      cytochrome b DNA sequences. This phylogeny is congruent with previous phenetic
      analyses of morphometric data for the lice. Comparison with a previously obtained
      phylogeny for the hosts indicates some degree of cospeciation. These cospeciation
      events are used to compare relative rates of evolution in the birds and their
      lice for the same segment of the cytochrome b gene. Cytochrome b is evolving two
      to three times more rapidly in lice than in birds, and louse cytochrome b is
      highly divergent compared to that of most other insects. Although generation time
      has been suggested as an explanation for the disparity in evolutionary rates
      between lice and their hosts, we suggest that the small effective population
      sizes of lice coupled with founder events occurring during transmission to new
      host individuals may be an important factor.

PMID- 9562987
TI  - Biogeographic origins of goannas (Varanidae): a molecular perspective.
AB  - This project aims to clarify the phylogenetic relationships among the extant
      species of Varanus in order to elucidate the origins of Varanidae, using DNA
      sequences. Results obtained for a minimum of 662 nucleotides of 12S rRNA sequence
      data from each of 21 extant species of Varanus indicate that the Australian
      varanids form a single monophyletic clade and also suggest that within the
      Australian varanids, members of the subgenus Odatria (pygmy monitors) may from a
      clade separate from those in the subgenus Varanus (large monitors). The Asian
      species appear to be sister taxa to the Australian species, while the two African
      species investigated were most divergent, suggesting that the Varanidae are not
      Gondwanic in origin. Hypothesis testing analyses were performed and involved
      constraining the 12S sequence data according to previously described topologies
      and testing the difference using parametric and nonparametric statistics. The
      phylogeny generated using 12S sequence data was statistically different from
      previously described morphological trees, while there was some support for
      topologies based on chomosomal and immunological datasets. Overall, our results
      suggest that the Australian species may be derived from an Asian source and are,
      therefore, in agreement with the hypothesis based on the fossil record suggesting
      that Varanidae may be Asian in origin.

PMID- 9562989
TI  - Molecular mechanisms of bacterial pathogenicity.
AB  - Cautious optimism has arisen over recent decades with respect to the long
      struggle against bacteria, viruses, and parasites. This has been offset, however,
      by a fatal complacency stemming from previous successes such as the development
      of antimicrobial drugs, the eradication of smallpox, and global immunization
      programs. Infectious diseases nevertheless remain the world's leading cause of
      death, killing at least 17 million persons annually [61]. Diarrheal diseases
      caused by Vibrio cholerae or Shigella dysenteriae kill about 3 million persons
      every year, most of them young children: Another 4 million die of tuberculosis or
      tetanus. Outbreaks of diphtheria in Eastern Europe threatens the population with
      a disease that had previously seemed to be overcome. Efforts to control
      infectious diseases more comprehensively are undermined not only by socioeconomic
      conditions but also by the nature of the pathogenic organisms itself; some
      isolates of Staphylococcus aureus and Enterobacter have become so resistant to
      drugs by horizontal gene transfer that they are almost untreatable. In addition,
      the mechanism of genetic variability helps pathogens to evade the human immune
      system, thus compromising the development of powerful vaccines. Therefore
      detailed knowledge of the molecular mechanisms of microbial pathogenicity is
      absolutely necessary to develop new strategies against infectious diseases and
      thus to lower their impact on human health and social development.

PMID- 9562988
TI  - Phylogenetic relationships of the western North American phoxinins
      (Actinopterygii: Cyprinidae) as inferred from mitochondrial 12S and 16S ribosomal
      RNA sequences.
AB  - Parsimony analysis of the mitochondrial 12S and 16S rRNA sequences of North
      American phoxinin taxa indicated the existence of three major clades, the Western
      Clade, the Creek Chub Clade, and the Open Posterior Myodome Clade. The
      monophyletic Western Clade identified in this paper contained fewer taxa than
      that identified by previous authors. This clade contained species restricted to
      drainages west of the Continental Divide, such as Gila, Acrocheilus, Relictus,
      Eremichthys, Siphateles, Ptychocheilus, Lavinia, and Orthodon, and the wide
      ranging genus Phoxinus found in eastern North America and Eurasia. Within this
      Western Clade Phoxinus was the basal sister group. Gila was recognized as a
      monophyletic group exclusive of Siphateles and Snyderichthys, clades
      traditionally recognized as subgenera of Gila. The genus Gila was most closely
      related to the genus Acrocheilus and together these formed the sister group to
      the genus Relictus. These relationships were supported independent of weighting
      schemes used in analyses. Identification of Phoxinus as the basal sister taxon of
      the Western clade implies that other major clades of North American Phoxinins
      likely have Asian or European relatives.

PMID- 9562991
TI  - Induction of a gravity-related response by a single receptor cell in an insect.

PMID- 9562990
TI  - Societal and commercial issues affecting the future of biotechnology in the
      United States: a survey of researchers' perceptions.
AB  - A 1995 survey of 1,257 U.S. recombinant DNA researchers assessed how they view
      outside factors affecting their work, including public and media attention;
      regulation; funding; international competition; commercialization of research and
      university/ industry collaboration; health care reform efforts; and patenting
      laws and policies. Generally, respondents view public attention as-having had
      positive effects on biotechnology progress, but they are concerned about the
      decrease in R&D funding, especially from government; the loss of scientific
      openness and basic-research quality caused by academic/industrial collaboration;
      international competition, particularly from Japan and Germany; overly stringent
      regulations that control R&D processes rather than products; inefficient
      regulatory agencies focused on irrelevant criteria; and threats to basic
      biomedical research from the short-term cost focus of managed-care companies.

PMID- 9562992
TI  - Otoacoustic emissions from a nonvertebrate ear.

PMID- 9562993
TI  - Solar UV monitor with yeast and the possibility of estimating ozone-layer
      thickness.

PMID- 9562994
TI  - Deviations in circadian rhythms of the core temperature in color-deficient
      subjects.

PMID- 9562995
TI  - Taurine and histamine: low molecular compounds in prey hemolymph increase the
      killing power of spider venom.

PMID- 9562996
TI  - [Applications of cortical magnetic stimulation].
AB  - In the last decade, a new electrophysiological tool has become available since
      the development of painless magnetic stimulators able to activate the primary
      motor cortex and the motor roots in conscious man. Therefore, it became possible
      to measure the conduction time within fast-conducting central motor pathways by
      substracting from the total latency of muscle responses elicited by cortical
      stimuli the conduction time in peripheral nerves. This technique proved sensitive
      enough to illustrate early abnormalities of central motor conduction in various
      neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis,
      cervical spondylotic myelopathy, degenerative ataxias or hereditary spastic
      paraplegias. When recorded early after stroke, motor evoked potentials are also a
      valuable tool to predict functional outcome. They can also illustrate subtle
      pathophysiological disturbances in diseases where there is no direct involvement
      of central motor pathways such as Parkinson's disease, dystonia or epilepsy.
      Magnetic cortical stimulation also offers unique opportunities to explore
      intracerebral inhibitory and excitatory circuits and mechanisms of brain
      plasticity. The recent development of rapid rate stimulators also enables
      functional studies of non-motor cerebral regions such as visual or frontal
      cortices. Moreover, rapid rate stimulation seems useful in the treatment of drug
      resistant depression but the safety of this procedure, particularly with regard
      to the production of seizures or kindling, remains to be fully documented.

PMID- 9562997
TI  - Increased cortical inhibition induced by apomorphine in patients with Parkinson's
      disease.
AB  - The electromyographic silent period following the motor potential evoked by
      cortical magnetic stimulation is decreased in parkinsonian patients. In this
      study we investigated whether the decrease in the silent period is connected only
      with parkinsonian symptoms. We evaluated the effect of apomorphine (a potent and
      rapid dopamine-agonist) on the changes in the peripheral and central silent
      period in 29 patients with Parkinson's disease and in two patients affected by
      multisystem atrophy (MSA). Apomorphine injection was found to induce a
      significant improvement in the central silent period in parkinsonian patients but
      not in the MSA patients, suggesting a relation between the clinical parkinsonian
      symptoms (akinesia and rigidity) and the silent period duration. The central
      silent period changes after apomorphine injection could be used as an adjunctive,
      safe and effective diagnostic tool to assess dopamine responsiveness of
      parkinsonian syndromes.

PMID- 9562998
TI  - Evaluation of early motor and sensory evoked potentials in cervical spinal cord
      injury.
AB  - To determine the efficacy of motor evoked potentials (MEP) and sensory evoked
      potentials (SEP) in the assessment of severe cervical injury, 17 subjects with
      severe cervical injury were studied. During the 1st week post-injury and post
      surgical treatment, all subjects were submitted to electromyogram (EMG)
      recordings, dermatomal somatosensory evoked potentials (D.SEP), posterior tibial
      nerve somatosensory evoked potentials (PTN.SEP), MEP and bilateral cervical
      electrical stimulations with recording of the diaphragm. For the D.SEP, the
      latencies of the N9 and N20 responses and the conduction time (N9-N20) were
      measured in the upper limbs; the latencies of the P40 and P60 responses were
      measured in the lower limbs. MEP were recorded from distal upper and lower limb
      muscles following transcranial electrical stimulation of the cortex. (Magnetic
      stimulation was not indicated because of implanted metallic material in the
      cervical skull of many patients.) A SEP and MEP grading system was used to
      improve the assessment of different root neurological levels. In patients with
      incomplete lesions PTN.SEP, D.SEP and MEP responses could be recorded in
      territories that were clinically deficient. Patients with complete lesions and
      absent SEP and MEP responses had a poor outcome. A good correlation was found
      between the severity of the spinal cord injury and SEP grading. For MEP, the
      presence or absence of intercostal responses (C4) to cervical and cortical
      stimulation was the best prognostic indicator. The combined electrophysiological
      exploration of MEP and SEP proved to be a useful tool for monitoring patients
      with severe spinal cord injury.

PMID- 9562999
TI  - [Correlations between clinical deficits, motor and sensory evoked potentials and
      radiologic aspects of MRI in malformative syringomyelia. 27 Cases].
AB  - Twenty-seven patients (15 males, 12 females, age range: 16-66 years) were
      admitted for malformative syringomyelia diagnosed on MRI with measures of syrinx
      extending and transverse diameter. Posterior tibial somatosensory evoked
      potentials (PT SEP), median (M SEP), trigeminal (V3 SEP), brain stem auditory
      evoked potentials (BEAP), cortical and cervical motor evoked potentials (MEP)
      were correlated with clinical and radiological findings. SEP abnormalities were
      not correlated with the duration of symptoms. PT SEP proved to be more sensitive
      than M SEP. MEP abnormalities were very frequent (87% of the cases), even without
      clinical motor deficits. Trigeminal SEP were more sensitive than BEAP which were
      not related to the presence of associated cranio-vertebral abnormalities. We
      found no significative relationship between clinical and radiological results.
      Moreover, there was a positive relationship between electrophysiological and
      radiological results: abnormal trigeminal SEP were detected in 85% of the
      patients with high cervical syringomyelia. In all cases, trigeminal SEP and MEP
      should be done in association with M and PT SEP as both of them detect
      subclinical evidence of spinal cord dysfunction in syringomyelia.

PMID- 9563000
TI  - [International literature review concerning evoked potentials in 1997].

PMID- 9563002
TI  - [High resolution EEG: recent developments and a new concept of EEG].

PMID- 9563001
TI  - [Sleep in 1997].

PMID- 9563003
TI  - Difluoromethylornithine antagonizes taxol cytotoxicity in MCF-7 human breast
      cancer cells.
AB  - Taxol is a naturally occurring anticancer agent. We studied the combined effects
      of taxol with 0.1 mM of the ornithine decarboxylase inhibitor alpha
      difluoromethylornithine (DFMO) in the MCF-7 human breast adenocarcinoma cell
      line. The effects of taxol on MCF-7 cells were evident at 0.05-1 microM and the
      half-maximum inhibition was calculated to be 0.05 microM. Although the cells in
      the control group continued to proliferate during an 8-day growth period, cells
      in the taxol-treated group showed approximately 78% inhibition on day 6 and
      approximately 92% inhibition on day 8. The combined effects of different
      concentrations of taxol with 0.1 mM DFMO for 48 h showed that DFMO reversed the
      cytotoxicity of taxol. The combined effects of 0.5 microM taxol and 0.1 mM DFMO
      over an 8-day period resulted in the reversal of taxol cytotoxicity by 74% on the
      sixth day of culture. Pretreatment and posttreatment with 0.1 mM DFMO protected
      the MCF-7 human breast adenocarcinoma cells from the cytotoxic effect of taxol.
      Polyamine levels were inhibited in cells treated with DFMO for 24 h. In a
      separate experiment, we verified that the addition of exogenous putrescine along
      with taxol and DFMO to cultures for 48 h restored the cytotoxic effects of taxol.
      Following exposure to 0.5 microM taxol, over 59% of MCF-7 cells were in G2/M
      phase. DFMO (0.1 mM) showed only a slight increase in the G1 phase of the cell
      cycle. However, in cells treated with taxol and DFMO, there was no change in the
      percent of cells in the G2/M phase compared to taxol-treated cells. Therefore,
      depletion of cellular polyamines may not interfere with cell cycle changes
      induced by taxol. Treatment of MCF-7 cells with 0.5 microM taxol resulted in the
      fragmentation of genomic DNA, indicating apoptosis, whereas the combined effects
      of taxol with DFMO inhibited DNA fragmentation.

PMID- 9563004
TI  - Model of malignant pleural effusion of human lung adenocarcinoma in SCID mice.
AB  - Malignant pleural effusion (PE) is a frequent problem in lung cancer. In this
      study, we established a model of malignant PE of human adenocarcinoma cells, PC
      14, in SCID mice. Intravenously injected PC-14 cells formed colonies in the lungs
      as early as week 4 after tumor inoculation, and produced bloody PE in all
      recipient SCID mice by week 8. Pretreatment of SCID mice with anti-mouse IL-2
      receptor beta chain antibody (TM-beta 1) to deplete natural killer (NK) cells
      markedly promoted the production of bloody PE and metastases to multiple organs,
      such as the lungs, liver, kidneys, and lymph nodes 4 weeks after tumor
      inoculation. Histological studies indicated that PC-14 cells formed colonies in
      the lungs, and then invaded the pleura and spread to the pleural cavity. To
      establish cell lines with a high potential to produce PE, we harvested PE,
      expanded the tumor cells in vitro, and injected them into SCID mice again. By
      four in vivo selection cycles in this way we obtained PC-14-PM4 cells, which
      produce lung metastases and PE earlier than PC-14 cells. The survival of SCID
      mice inoculated with PC-14-PM4 cells was significantly shorter than that of mice
      inoculated with PC-14 cells. The expressions of adhesion molecules, such as CD44,
      CD49d, ICAM-1, and MHC class I, on PC-14-PM4 cells tended to increase compared
      with PC-14 cells. These changes of adhesion molecules seem to be one of possible
      mechanisms involved in higher metastatic potential of PC-14-PM4 cells. PE models
      with PC-14 and PC-14-PM4 cells should be useful for biological and preclinical
      studies on malignant PE produced by human lung cancer.

PMID- 9563005
TI  - Preferential inhibition of glioblastoma cells with wild-type epidermal growth
      factor receptors by a novel tyrosine kinase inhibitor ethyl-2,5
      dihydroxycinnamate.
AB  - Epidermal growth factor receptor (EGFR) gene overexpression and mutations play an
      important role in the pathogenesis of a variety of malignant human cancers. In
      this study, we tested the effects of a novel EGFR tyrosine kinase inhibitor,
      ethyl-2,5-dihydroxycinnamate (EtDHC), against related human glioblastoma cell
      lines expressing specific forms of EGFR gene mutations. EtDHC more potently
      inhibited cell growth and DNA synthesis in glioblastoma cells with endogenous or
      overexpressed wild-type EGFR compared with those with truncated EGFR, by
      preferentially inhibiting the tyrosine kinase activity and autophosphorylation of
      the wild-type EGFR. Higher concentrations of EtDHC were required to inhibit cells
      expressing the truncated EGFR. These findings are the reverse of another highly
      specific tyrosine kinase inhibitor, tyrphostin AG 1478, which preferentially
      inhibited glioblastoma cells with truncated EGFR compared with those with wild
      type EGFR. The differential susceptibility of various glioblastoma cells to
      highly specific tyrosine kinase inhibitors is significant because human gliomas
      are composed of heterogeneous cells with subsets of cells expressing specific
      gene mutations. This cellular heterogeneity could be one of the reasons why tumor
      cells are resistant to chemotherapy. Thus, EtDHC, especially when in combination
      with drugs targeting other specific gene mutations (such as tyrphostin AG 1478),
      holds a significant potential for chemotherapy for human glioblastomas.

PMID- 9563006
TI  - Regulation of estrogen activity by sulfation in human MCF-7 breast cancer cells.
AB  - Estrogen metabolism is closely associated with the growth, progression, and
      treatment of breast cancer because many breast cancers are dependent upon
      estrogens for both growth and progression. Factors that affect the intracellular
      metabolism of estrogens may be critical in altering the effects of estrogens on
      breast cancer cells. MCF-7 cells have been used as a model system to study the
      effects of estrogens on breast cancer cellular growth. Because normal human
      mammary epithelial (HME) cells contain estrogen sulfotransferase (EST), which is
      involved in the inactivation of estrogens via sulfation, and MCF-7 cells do not
      possess this enzyme, the absence of EST may be critical to the growth of MCF-7
      cells in the presence of estrogens. To study the effects of EST on cellular
      growth, MCF-7 cells stably transformed with an EST expression vector were
      compared to control cells transformed with vector only. Sulfation of 20 nM E2
      occurs more rapidly with MCF-7 cells transformed with EST than with the control
      cells, thereby rendering E2 physiologically inactive. Additionally, these EST/MCF
      7 cells sulfate 20 nM 17 alpha-ethinylestradiol (EE2) at a rate similar to that
      for E2 but sulfate 20 nM diethylstibestrol (DES) much more slowly; these results
      correlate with the kinetic characteristics of EST for these steroids. EST/MCF-7
      cells require higher concentrations of E2 to stimulate growth than do control MCF
      7 cells, hypothetically because EST is inactivating E2 via sulfation, rendering
      it incapable of binding to the estrogen receptor (ER). The effects of EE2 are
      similar to those of E2 whereas DES is effective at lower concentrations because
      it is not inactivated by EST. Neither control nor EST/MCF-7 cells grow well in
      the complete absence of estrogens, as would be expected because MCF-7 cells are
      estrogen dependent. However, in medium that has not been treated to remove
      endogenous estrogens, EST/MCF-7 cells grow more slowly than control cells, most
      likely because EST is inactivating the estrogens in the medium, making them
      ineffective in stimulating growth. EST/MCF-7 cells possess EST at levels similar
      to HME cells and are less responsive to estrogens than are MCF-7 cells lacking
      EST. The loss of EST may be a factor in oncogenesis, which leads to altered
      estrogen metabolism in breast carcinoma cells.

PMID- 9563007
TI  - Synergistic action of quercetin and genistein in human ovarian carcinoma cells.
AB  - Ovarian carcinoma is the fourth most common cause of cancer death in women and
      there has been a steady increase in the age-adjusted cancer death rates in the
      past 25 years in the US. However, patients who become cisplatin resistant respond
      poorly to available cytotoxic agents; therefore, discovering novel targets for
      ovarian carcinoma is vital. Quercetin, an anticancer agent, arrests the cell
      cycle at G1 and S phase boundary. Genistein, a plant flavonoid, attacks the cell
      cycle at G2 and/or early M phases in most carcinoma cells. Quercetin and
      genistein block the phosphatidylinositol conversion to IP3 signal transduction
      pathway mainly by inhibiting 1-phosphatidylinositol 4-kinase (PI kinase, EC
      2.7.1.67) and 1-phosphatidylinositol 4-phosphate 5-kinase (PIP kinase, EC
      2.7.1.68), respectively. Because each drug attacks a different phase of the cell
      cycle and reduces IP3 concentration by attacking different signal transduction
      enzymes, we tested the hypothesis that the two drugs might be synergistic in
      human carcinoma cells. In human ovarian carcinoma OVCAR-5 cells in growth
      inhibition assay, the IC50S for quercetin and genistein were (mean +/- SE) 66 +/-
      3.0 and 32 +/- 2.5 microM; in clonogenic assays they were 15 +/- 1.2 and 5 +/-
      0.5 microM, respectively. When quercetin was added to the cultures of OVCAR-5
      cells followed 8 h later by genistein, synergism was observed in growth
      inhibition and clonogenic assays. The synergistic action of quercetin and
      genistein may be of interest in clinical treatment of human ovarian carcinoma.

PMID- 9563008
TI  - Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild
      type p53 gene in human ovarian carcinomas.
AB  - Mutations of the tumor suppressor wild-type p53 gene have been implicated in the
      development of resistance to anticancer drugs. We have examined the role of wild
      type p53 in resistance to cis-diamminedichloroplatinum (II) (CDDP) in human
      ovarian cancer cells using a recombinant adenovirus containing human wild-type
      p53 cDNA (Adwtp53). In this study we used the human ovarian A2780 tumor cells
      (wtp53), which are sensitive to CDDP and A2780/CP tumor cells
      (nonfunctional/mutant p53) and are resistant to CDDP. Studies show that
      introduction of wtp53 protein via adenovirus gene transfer into A2780/CP cells
      significantly sensitized these cells to CDDP cytotoxicity, indicating wtp53 was
      involved in resistance to CDDP. We found that introduction of wtp53 protein also
      resulted in growth arrest of A2780/CP tumor cells whereas the parent A2780 cells
      were significantly less sensitive to Adwtp53. This synthesis of wtp53 protein
      induced by Adwtp53 in A2780/CP cells resulted in a significant increase in the
      expression of Bax protein without significantly effecting the expression of bcl2
      protein, and induced a dose-dependent increase in the nucleosomal DNA
      fragmentation. The presence of CDDP further enhanced this apoptosis, causing a 30
      fold sensitization of A2780/CP cells to CDDP. These results indicate that
      mutation of p53 protein in A2780/CP ovarian tumor cells resulted in the
      resistance to CDDP and that combination of wtp53 gene and CDDP may result in
      sensitization of mutant p53-containing tumors to chemogenetherapy.

PMID- 9563009
TI  - The alternative H-ras protein p19 displays properties of a negative regulator of
      p21Ras.
AB  - In previous work, we demonstrated that expression of mammalian H-ras genes is
      controlled by alternative splicing. Mutational analyses indicated that most H-ras
      premessenger RNA (pre-mRNA) is not processed into mRNA for the usual p21Ras
      protein, but is recognized instead for processing through an alternative pathway
      that would produce mRNA for a hypothetical p19Ras protein, which would be a
      truncated form of p21 with a different carboxyl-terminus. We have raised the
      possibility that p19 could be a negative regulator of p21, but only small amounts
      of mature p19 mRNA could be detected and we had no evidence that the protein
      could be made. We now show by transient and stable transfection experiments that
      p19 can be produced from complementary DNA (cDNA) expression vectors in human 293
      cells, which express early adenoviral genes. However, p19 cDNA inhibited the
      formation of drug-selected colonies of Rat-1 cells and surviving colonies
      produced little p19. Colony formation and p19 expression were increased when the
      cDNA had mutations in the putative effector domain of p19 or when oncogenes
      believed to act downstream of p21Ras, such as adenoviral E1A, were included in
      the transfections. These results indicate that p19 can act as an inhibitor of
      p21. We also show that authentic p19 can be abundantly expressed in 293 cells
      from H-ras gene constructs with mutations favoring the alternative splicing
      pathway, which suggests that regulated splicing could support overproduction of
      p19 under natural conditions. Our work indicates that mutations abolishing
      alternative H-ras splicing may not only contribute to oncogenesis by increasing
      the production of p21, but also by interfering with the production of an
      antiproliferative H-ras activity.

PMID- 9563010
TI  - TNF-alpha induction of A1 expression in human cancer cells.
AB  - A1, a member of the Bcl-2 gene family, was originally identified as a hemopoietic
      specific early response gene. Later it was found that A1 was overexpressed in
      human stomach cancer tissues and was induced by tumor necrosis factor-alpha (TNF
      alpha) in human vascular endothelial cells. However, its expression in human
      cancer cells has not been well characterized. In the present study, we examined
      the expression of A1, as well as the antioxidant manganous superoxide dismutase
      (MnSOD), in four human thyroid carcinoma cell lines, two human pancreatic
      carcinoma cell lines, and two human prostate carcinoma cell lines. A1 mRNA was
      expressed in all four thyroid carcinoma cell lines. TNF-alpha induced A1 in a
      time- and dose-dependent manner. In contrast, A1 mRNA was not detectable in the
      pancreatic and prostate carcinoma cell lines in the presence or absence of TNF
      alpha. However, TNF-alpha induced manganous superoxide dismutase (MnSOD) mRNA in
      all the cell lines tested. Furthermore, an agonist antibody to the p55 TNF-alpha
      receptor induced A1, but the agonist antibody against p75 TNF-alpha receptor did
      not have this effect. The results indicate that A1 is expressed in human thyroid
      carcinoma cells and TNF-alpha induces A1 through the p55 TNF-alpha receptor
      mediated pathway.

PMID- 9563012
TI  - The value of early postoperative oesophagography following repair of oesophageal
      atresia.
AB  - The aim of the study was to examine the relationship between anastomotic leaks
      and the development of symptomatic anastomotic strictures after primary repair of
      oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) and
      the prognostic value of the anastomotic appearance on postoperative
      oesophagography. The records and X-ray films of 49 patients with OA with or
      without TOF admitted between January 1990 and June 1995 were reviewed
      retrospectively. Of these, 37 had a primary repair (34 immediate and 3 delayed)
      and a postoperative contrast swallow was done between day 5 and day 30 (median
      day 7). Radiological leaks were documented. In addition, the maximum transverse
      diameters of the upper pouch and anastomotic region and the length of the
      anastomotic narrow segment were measured; the ratio of upper-pouch diameter to
      that of the anastomosis was calculated (anastomotic index, AI). The need for
      dilatation of symptomatic anastomotic strictures and for repeat dilatation as a
      separate episode were documented. Of the 37 patients, 4 developed an anastomotic
      leak (11%), 3 radiological and 1 clinical. A symptomatic stricture occurred in
      55% of patients. There was no correlation between a leak and later development of
      a symptomatic stricture, although the small number of patients with leaks
      precluded definite conclusions. No radiological leak progressed to a clinical
      leak. There was no correlation between the AI or the length of the anastomotic
      narrow segment and the need for dilatation, the need for repeat dilatation, or
      the number of dilatations. In this study, the presence of a leak, the AI, and the
      length of the narrow segment on early postoperative contrast swallow did not
      correlate with the later development of a symptomatic stricture. A radiological
      leak was of no clinical significance. Since major leaks are apparent clinically,
      an early routine contrast study did not influence management and is not
      necessary.

PMID- 9563011
TI  - Mapping specific protein-protein interactions within the core component of the
      breast cell DNA synthesome.
AB  - We have previously described the isolation and characterization of an intact
      multiprotein complex for DNA replication, designated the DNA synthesome, from
      human breast cancer cells and biopsied human breast tumor tissue. The purified
      DNA synthesome was observed to fully support DNA replication in vitro. We had
      also proposed a model for the breast cell DNA synthesome, in which DNA
      polymerases alpha, delta, and epsilon, DNA primase, and replication factor C (RF
      C) represent members of the core component, or tightly associated, proteins of
      the complex. This model was based on the observed fractionation, chromatographic,
      and sedimentation profiles for these proteins. We report here that poly(ADP
      ribose)polymerase (PARP) and DNA ligase 1 are also members of the breast cell DNA
      synthesome core component. More importantly, in this report we present the
      results of coimmunoprecipitation studies that were designed to map the protein
      protein interactions between several members of the core component of the DNA
      synthesome. Consistent with our proposed model for the breast cell DNA
      synthesome, our data indicate that DNA polymerases alpha and delta, DNA primase,
      RF-C, as well as proliferating cell nuclear antigen (PCNA), tightly associate
      with each other in the complex, whereas DNA polymerase epsilon, PARP, and several
      other components were found to interact with the synthesome via a direct contact
      with only PCNA or DNA polymerase alpha. The association of PARP with the
      synthesome core suggests that this protein may serve a regulatory function in the
      complex. Also, the coimmunoprecipitation studies suggest that the three DNA
      polymerases alpha, delta, and epsilon all participate in the replication of
      breast cell DNA. To our knowledge this is the first report ever to describe the
      close physical association of polypeptides constituting the intact human breast
      cell DNA replication apparatus.

PMID- 9563013
TI  - Esophageal replacement with colon in children.
AB  - Between 1974 and 1994, 25 colonic interposition procedures were performed for
      esophageal replacement in 23 cases of esophageal atresia (EA) and 2 corrosive
      strictures. Nine patients had one-stage and 16 had two-stage reconstructions. The
      transthoracic route was used in 16 cases (64%) and the retrosternal route in 9
      (36%). Average age at the time of operation in EA patients was 17 months (range
      12-33), and the children with corrosive injuries were 3 and 6 years old. Mean age
      at follow-up was 11.8 years (2.3-20.5 years). There was no mortality in the
      series. One patient developed full-graft necrosis and had a gastric pull-up
      procedure later. One child had partial graft necrosis (3 cm at the cervical end),
      however, enough colon was available for reconstruction. Ten patients developed a
      leak from the cervical anastomosis (40%) and 7 developed a stricture at the
      cervical esophago-colonic anastomosis (28%). The strictures were treated by
      repeated esophageal dilatation, and 3 patients required revision of the
      anastomosis (12%). Other complications included acid reflux in 2 cases (8%),
      small-intestinal obstruction in 1 (4%), redundancy of the colon in 1 (4%), and
      chest infections in 2 (8%). Follow-up included assessment of the patient's
      symptoms, serial growth measurements (height and weight), and where relevant,
      endoscopy and a contrast swallow or meal. There was a 52% improvement in weight
      and height percentiles post-operatively. Each of the 19 patients who had barium
      swallows showed rapid transit and emptying without any significant delay or hold
      up. Overall long-term results were excellent in 13 patients (52%), good in 7
      (28%), and fair in 5 (20%). The colon conduit thus provides an excellent
      substitute esophagus in pediatric patients.

PMID- 9563014
TI  - The use of collagen-coated vicryl mesh for reconstruction of the canine cervical
      esophagus.
AB  - Collagen-coated vicryl mesh (CCVM) was used experimentally to patch partial and
      total segmental defects in the canine cervical esophagus. The esophageal healing
      process over a 6-month period with successful incorporation of the CCVM and
      esophageal wall regeneration are described. Twenty-two (91.7%) of 24 dogs
      survived the procedure without any evidence of esophageal stricture or dysphagia.
      CCVM has proved to be a suitable material for substitution of esophageal tissue
      in the canine model. Its clinical use in congenital and acquired esophageal
      lesions should be considered only pending further experimental laboratory work.

PMID- 9563015
TI  - Congenital esophageal atresia with tracheoesophageal fistula occurring in both
      members of dizygotic twins.
AB  - The authors present a pair of dizygotic twins with congenital esophageal atresia
      with tracheoesophageal fistula who underwent successful single-stage surgical
      repair. To our knowledge, this is the second set of dizygotic twins with this
      congenital anomaly in the literature.

PMID- 9563016
TI  - Congenital para-oesophageal hiatal hernia in infancy.
AB  - Congenital para-oesophageal hiatal hernia (PEHH) is a rare problem in infancy,
      however, it constitutes a clinical entity that mandates surgical repair once the
      diagnosis is made. In the paediatric age group, acquired PEHH has been described
      as a major complication in a number of patients who were treated surgically for
      gastro-oesophageal reflux (GER) by Nissen fundoplication. PEHH is a frequently
      encountered condition in elderly patients; it accounts for 5% of diaphragmatic
      hiatal hernias. In both paediatric and adult patients PEHH, whether congenital or
      acquired in origin, is usually associated with potentially lethal complications
      such as gastric volvulus, incarceration, and perforation. In clinical practice
      true PEHH is extremely rare. The term has been expanded to include large gastric
      hiatal hernias where most of the stomach and the gastro-oesophageal junction are
      in the chest. Six infants with congenital PEHH are presented, together with an
      attempt to understand its possible aetiology and a review of its current surgical
      management.

PMID- 9563017
TI  - Septic complications after splenectomy for sickle cell sequestration crisis.
AB  - Patients with sickle cell disease (SCD) are predisposed to infections. There is a
      paucity of recent information on the incidence of post-splenectomy infectious
      complications in these patients. The purpose of this study was to determine
      whether splenectomy increases infectious complications in SCD. Twenty-nine
      patients with SCD had splenectomy for sequestration crises at our hospital
      between 1988 and 1992; 16 of them received all of their follow-up care at our
      institution. These 16 charts were reviewed for infectious-related admissions,
      hospital days, days of i.v. antibiotics, positive cultures, and episodes of
      sepsis. For each patient, these parameters in the pre- and postoperative period
      were compared and expressed as number per year. The mean age at time of
      splenectomy was 2.5 +/- 0.4 years and the mean follow-up was 4.5 +/- 0.4 years.
      There was no significant difference in the pre- and postoperative periods for
      admissions, hospital days, days of i.v. antibiotics, positive cultures, or
      episodes of sepsis per year. There were also no operative deaths. The incidence
      of pre-splenectomy sepsis was 0.04 +/- 0.03 episodes per year compared to 0.09 +/
      0.04 (P = ns) episodes/year after splenectomy. Sepsis occurred at an average of
      20.8 (range 2-30) months postoperatively; Streptococcus pneumoniae was the most
      common causative organism. The total mortality after splenectomy in SCD patients
      was 3.4% (1/29) over a nearly 5-year period. Although infections are common in
      children with SCD, there was no increase in infections or episodes of sepsis in
      SCD patients who underwent splenectomy.

PMID- 9563018
TI  - Traumatic injuries of the alimentary tract in children.
AB  - Traumatic alimentary tract (AT) perforations in children secondary to
      instrumentation, though rare, can occur at any age, especially in neonates and
      young infants. Awareness of such a possibility is essential for prompt management
      to be initiated. Over a 10-year period (1986-1995), eight pediatric patients with
      AT perforations secondary to instrumentation were managed at the American
      University of Beirut Medical Center. Five had upper AT injuries that included
      three hypopharyngeal, one esophageal, and one gastric lesion. The remaining three
      patients had lower AT injuries involving the transverse colon in one and the
      rectum in two. All the patients but two (one with a hypopharyngeal and one with
      an esophageal injury) were managed surgically and all survived. These rare
      injuries are discussed in addition to the preventive measures to be taken.

PMID- 9563019
TI  - Nonoperative management of intra-abdominal bleeding due to blunt trauma in
      children: the risk of missed associated intestinal injuries.
AB  - Nonoperative management of intra-abdominal bleeding (IAB) from blunt injuries in
      children has been advocated for many years. Nonoperatively managed patients,
      however, are at risk for missed associated intestinal injuries. To evaluate this
      question, we reviewed the charts of 120 children who had traumatic IAB; 106 were
      initially managed nonoperatively and observation failed in 2. Fourteen underwent
      emergency operation. Forty patients had isolated liver and/or splenic injuries
      while the others had injuries associated with several organs. During observation
      peritonitis developed in 3 patients and further radiologic examinations failed to
      confirm an intestinal injury. Diagnostic peritoneal lavage demonstrated
      contaminated blood and fecal particles from injured intestines in 3 patients;
      they underwent emergency operation at 10, and 26 h after admission. There was no
      mortality or morbidity associated with delayed treatment. These data suggest that
      the majority of patients with IAB may be successfully treated nonoperatively, but
      associated intestinal injuries should be suspected in all cases.

PMID- 9563022
TI  - The effect of an H2-receptor antagonist on small-bowel colonization and bacterial
      translocation in newborn rats.
AB  - Bacterial translocation (BT) is defined as the passage of enteric bacteria from
      the gastrointestinal tract to extraintestinal tissues. Bacterial overgrowth is
      one of the main promoting factors of BT, which is thought to play an important
      role in the pathogenesis of sepsis and necrotizing enterocolitis. It is believed
      that small-bowel colonization is established by bacterial spread through the
      rectum. Gastric acid is also involved in this process. An experimental study was
      designed for investigating the effect of gastric acid inhibition with the use of
      an H2-receptor antagonist on intestinal colonization and BT in newborn rats.
      Animals were divided into two groups: the ranitidine group (n = 20) received
      ranitidine 10 mg/kg per day intramuscularly for 5 days; the control group (n =
      30) received saline solution. Mesenteric lymph node, spleen, liver, stomach,
      small bowel/cecum, and large bowel specimens were obtained from each rat 5 days
      later and gram-negative and -positive aerobic bacteria identified by the use of
      chocolate and Endo agar. It is concluded that: (1) there was a strong correlation
      between gastric and small-bowel bacterial colonization in the ranitidine group;
      (2) no correlation between large-and small-bowel colonization could be
      demonstrated; and (3) BT occurred only in the ranitidine group.

PMID- 9563020
TI  - Plasma-to-lumen clearance of para-aminohippurate can replace 51Cr EDTA clearance
      in the evaluation of intestinal mucosal injury.
AB  - Intestinal mucosal injury of various degrees occurs in many clinical situations
      and is initially evidenced by altered mucosal permeability. The latter may be
      assessed in animal models by determination of plasma-to-intestinal lumen
      clearance of specific molecules, usually chromated 51Cr EDTA. The purpose of this
      study was to evaluate the usage of para-aminohippurate (PHA) as a substitute for
      the commonly used radioactive material, i.e., 51Cr-EDTA, in the evaluation of
      intestinal mucosal injury. An isolated loop of ileum was created in rats and
      constantly perfused with warmed normal saline. Both renal pedicles were ligated.
      Either 51Cr-EDTA (18.5 Bq/kg) or PAH (58 mg/kg) was injected i.v. Fifteen-minute
      intestinal ischemia was produced by clamping the superior mesenteric artery
      immediately after the end of an equilibration period. The perfusate was collected
      for 10 min prior to the initiation of intestinal ischemia, during the last 10 min
      of ischemia, and during the following three 10-min periods of reperfusion. Blood
      samples were collected at the end of each collection period for the determination
      of either PAH or 51Cr-EDTA concentrations and the calculation of either PHA or
      51Cr-EDTA plasma-to-lumen clearances. PAH and 51Cr-EDTA plasma-to-lumen
      clearances followed the same pattern in all five assessed periods with no
      statistical difference between the two. PAH plasma-to-lumen clearance is a
      feasible, reliable, and inexpensive method for the evaluation of
      ischemia/reperfusion injury to the intestinal mucosa. It can safely replace the
      commonly used method in animal models that utilizes radioactive materials such as
      51Cr-EDTA.

PMID- 9563021
TI  - Does gut atresia cause polyhydramnios?
AB  - Fetal gut atresia is variably associated with polyhydramnios. In order to
      determine which pregnancies will develop polyhydramnios, the case notes of 80
      babies with gut atresia and stenosis were reviewed. Maternal polyhydramnios
      developed in all cases of pure oesophageal atresia (n = 8), all cases of Type III
      duodenal atresia (DA) with a non-bifid bile duct (n = 8), 80% of cases with type
      I DA (n = 10), and 24% of atresias of the small intestine (n = 34).
      Polyhydramnios did not develop in any case where there was not total obstruction
      except in 1 baby with DA and a bifid bile duct (BBD). These included stenosis of
      the oesophagus and duodenum (n = 17) and DA type III with a BBD (n = 3). These
      results support the role of fetal swallowing and fluid absorption by the fetal
      gastro-intestinal tract in the regulation of amniotic fluid volume.

PMID- 9563023
TI  - Rectal biopsy for Hirschsprung's disease: what is the optimum method?
AB  - During a 3-year period, 258 infants and children underwent rectal biopsy to
      exclude Hirschsprung's disease (HD) and related disorders; 32 (12%) were found to
      have HD. Major morbidity occurred in 3 (2%) of 148 patients undergoing rectal
      suction biopsy (RSB) and 22 (13%) of 168 suction biopsies were inadequate for
      diagnosis. In 102 children over 6 months of age, Storz rectal cup biopsy forceps
      were used with no significant morbidity and adequate biopsies were obtained in
      96% of cases. Open rectal biopsy was performed in 8 patients. The RSB tube is
      safe and reliable, but attention to technique is important. For children over 6
      months of age undergoing rectal biopsy for HD, the Storz rectal cup biopsy
      forceps yields superior results.

PMID- 9563024
TI  - Principal modifications of the Duhamel procedure in the treatment of
      Hirschsprung's disease. Analysis based on results of an international
      retrospective study of 2,430 patients.
AB  - In the literature, many articles refer to the DUHAMEL technique or some of its
      modifications in the treatment of Hirschsprung's disease, however, no complete
      review of all of them has been published to date. The authors present an analysis
      of the principal modifications of this technique based on the results of an
      international retrospective survey that evaluated a series of 2,430 patients as
      well as data from the literature. The important role of the internal anal
      sphincter in the physiology of continence is emphasized; understanding its
      function is an imperative prerequisite for a successful Duhamel procedure. The
      original technique, which used two crushing Kocher clamps as proposed by Duhamel
      in 1956, as well as a majority of the modifications with various spur-crushing
      instruments are no longer in use. At present, surgeons generally use staplers for
      the colorectal anastomosis.

PMID- 9563025
TI  - Anorectal function and endopelvic dissection in patients with repaired
      imperforate anus.
AB  - Fifty-eight patients with anorectal malformations were closely followed up for
      postoperative anorectal function. Constipation was noted shortly after
      anorectoplasty in 10 of 28 low anomalies (35.7%) treated with limited sagittal
      anorectoplasty (LSARP), in 18 of 25 high or intermediate anomalies (72.0%)
      treated with posterior sagittal anorectoplasty (PSARP), but in none of 5 high or
      intermediate anomalies treated with Rehbein's mucosa-stripping endorectal pull
      through and anterior sagittal perineal anorectoplasty (R-ASAP). The constipation
      resolved mostly within 1-2 years after repair under conservative management, but
      persisted beyond 2 years after repair in 3/25 children with LSARP and 10/25 with
      PSARP. Anal soiling was noted in 1/23 (4.3%) LSARP and 6/22 (27.3%) PSARP
      patients, but normal anorectal function was attained in 20/23 LSARP (86.9%) and
      11/12 PSARP patients (50.0%) by the time of toilet training. Manometric studies
      disclosed that the resting rectal pressure (RRP) was lower and the anorectal
      pressure gradient (ARPG) higher in the constipated than the non-constipated
      children, while the RRP was higher and the ARPG lower in the soiled than the non
      soiled patients. The ARPG after R-ASPA was close to that of non-constipated and
      in between that of the constipated and soiled patients. The rectoanal sphincter
      inhibitory reflex was not related to defecation status or surgical procedures,
      but showed a tendency toward positive conversion with time or after exclusion of
      esctatic terminal bowel in the severely constipated. It is concluded that
      anorectal function in patients with repaired imperforate anus seems to be more
      affected by the extent of endopelvic dissection than by preservation of the
      terminal bowel or sphincter muscles.

PMID- 9563026
TI  - Results of surgery for vesicoureteral reflux in children: 6 years' experience in
      an Asian country.
AB  - From January 1990 to December 1995, a total of 181 patients underwent
      reimplantation of 318 ureters for primary vesicoureteral reflux (VUR); 87.8%
      received bilateral reimplantation. Surgical indications included breakthrough
      infection (35%), high-grade (> or = IV) reflux (33%), or both (29%). The
      operative success rate was 99.4% at 3 months postoperatively and 100% ultimately.
      The complications included: contralateral sequential reflux in 3.9%,
      postoperative bladder diverticula in 1.1%, postoperative urinary infection in
      1.1%, residual reflux in 0.3%, postoperative vesicoureteral stenosis in 0.3%, and
      slippage of the drainage tube in 0.3% of cases. Two patients had renal failure
      due to VUR that was proven by renal biopsy (one 4-year-old and one 8-year-old).
      The incidence of associated anomalies was higher than in the normal population.
      The average number of hospital admission days was 7.9 (3-63). After 1992, no
      ureteral stent was left in postoperatively. All patients received prophylactic
      antibiotics for 3 months postoperatively until the VUR disappeared. The surgical
      results were satisfactory in this series.

PMID- 9563028
TI  - Cryptorchidism in boys with congenital abdominal wall defects.
AB  - Cryptorchidism (CPT) has been suggested to be common in boys with congenital
      abdominal wall defects (CAWD). It has been hypothesized that the low intra
      abdominal pressure in both omphalocele (OMP) and gastroschisis (GS) and brain
      malformations in patients with OMP contribute to the high incidence of CPT. To
      determine the incidence of CPT in boys with OMP and GS and to assess the
      relationship of CPT to the size of the AWD, prematurity, and concomitant
      anomalies, the hospital records and autopsy reports of 113 boys with CAWD (OMP n
      = 75; GS n = 38) were reviewed. Twelve (16.0%) boys with OMP had undescended
      testes; 5 (41.0%) of those had bilateral and 4 (23.5%) intraabdominal undescended
      testes. The occurrence of CPT in OMP patients did not correlate with the size of
      the AWD, birth weight, or gestational age. However, congenital cardiac anomalies
      and cleft lip and palate were significantly more common (P < 0.05) among those
      with CPT. Two (5.0%) boys with GS, both of whom were born prematurely, had
      unilateral CPT. In patients with OMP, the incidence of CPT was significantly
      higher than that of healthy children. There was a correlation between CPT and
      congenital midline defects such as cardiac anomalies and cleft lip and palate. In
      patients with GS, the incidence of CPT only slightly exceeded that of normal
      children and may have been related to prematurity.

PMID- 9563027
TI  - Paratubal cysts in young females as an incidental finding in laparotomies
      performed for right lower quadrant abdominal pain.
AB  - Paratubal cysts represent remnants of the paramesonephric or mesonephric duct,
      the former being more common. Most of them are asymptomatic, but they may rarely
      give rise to clinical problems due to enlargement or torsion. In this study, we
      looked for paratubal cysts or other pathological lesions of the right uterine
      adnexa in young females operated upon for right lower quadrant (RLQ) abdominal
      pain. Our material consisted of 338 white female patients aged 4-14 years.
      Laparotomy revealed only acute appendicitis in 283 cases, while 44 had acute
      appendicitis plus a coincidental paratubal cyst. Most of these cysts were smaller
      than 1 cm in diameter. However, 2 additional cases had torsion of a large
      paratubal cyst, while 5 had a ruptured corpus luteum. We suggest that a thorough
      search of the right adnexa for the presence of paratubal cysts during
      laparotomies performed for RLQ pain is a useful procedure. This approach also
      allows detection of other pathological lesions of the right adnexa that often
      produce symptoms similar to acute appendicitis.

PMID- 9563029
TI  - Does circumcision alter the periurethral bacterial flora?
AB  - A prospective study of 25 boys who underwent circumcision for medical reason was
      performed. Specimens of periurethral bacterial flora were taken before operation
      as well as 3 weeks after surgery, so that each boy acted as his own control.
      Before circumcision, 13 (52%) harboured uropathogenic organisms (Escherichia coli
      and other coliforms, Enterococcus spp, Proteus spp, Pseudomonas spp, and
      Klebsiella spp); after circumcision, none of the boys had uropathogens, the only
      organisms cultured from the periurethral region being skin commensals. We
      postulate that circumcision converts a 'cul-de-sac' that is a reservoir of
      organisms capable of causing ascending urinary tract infection into a surface
      colonised by natural skin organisms. This study provides circumstantial evidence
      supporting the idea that circumcision in well-selected patients may confer
      protection from urine infection.

PMID- 9563030
TI  - Minimally invasive surgery does not improve the outcome in a model of
      retroperitoneal murine neuroblastoma.
AB  - Minimally invasive surgery (MIS) for cancer patients has become widely accepted
      in general surgery, however, it has not completely replaced the standard open
      operative procedures in pediatric oncology. The aim of this study was to evaluate
      the host relationship following MIS in a murine model of retroperitoneal
      neuroblastoma (NB) Immature, 5- to 7-week-old male A/J mice weighing 18-23 g were
      inoculated with either C1300 or TBJ NB in the left retroperitoneal space. At 4
      days (early stage) or 11 days (late stage) following tumor inoculation, the
      animals underwent a laparotomy or pneumoperitoneum with carbon dioxide under
      general inhalational anesthesia. Animal survival, tumor growth, and postoperative
      changes in body weight were observed. In the model of subcutaneous TBJ NB,
      distant metastases following the laparotomy or MIS technique were also evaluated.
      Each surgical group had a sample size > or = 12, and data were statistically
      analyzed by ANOVA and the chi-square test where appropriate. P < 0.05 was
      considered to be significant. There were no significant differences in animal
      survival, tumor growth, or distant metastases among surgical groups in any
      combination of type and stage of tumor. The only salutary influence of MIS was
      seen in a model of early-stage NB, where the decrease in body weight on
      postoperative day 7 was preserved when compared to post-laparotomy weight loss.
      We conclude that when compared to conventional laparotomy, the MIS access
      technique does not influence the outcome in a model of retroperitoneal murine NB.

PMID- 9563031
TI  - Siamese twins in the United Arab Emirates.
AB  - In the years 1985-1992, ten pairs of conjoined twins were born in the United Arab
      Emirates (UAE): one dicephalus, two teratopagi, and seven thoracoomphalopagi, one
      of which was still-born and three who were cared for in other hospitals. The
      first pair of thoraco-omphalopagus twins died of acute lymphoblastic leukaemia 6
      months after successful separation. The management of the third set of twins gave
      rise to moral and ethical problems often encountered in such situations, while
      one of the teratopagi was a unique case of a parasite projecting from the mouth
      of the normal twin.

PMID- 9563032
TI  - Preputial intussusception or acquired megaprepuce.
AB  - Preputial intussusception, or acquired megaprepuce, is a clinical condition whose
      incidence is increasing. It results from infolding of the outer preputial skin,
      obstruction of urinary flow, and the development of a phimosis. With time the
      process continues, resulting in a distinctive clinical picture. Treatment by
      early circumcision cures the problem and allows resolution of the sequelae.

PMID- 9563033
TI  - Operative complications of hernia repair in childhood.
AB  - In a training center, 1,131 inguinal hernias were repaired in 1,000 consecutive
      patients in 6 years. The documents of these patients were reviewed
      retrospectively for surgical complications. A total of 38 complications were
      encountered in 35 patients, including wound infection (1.9%), recurrence (0.9%),
      tethered testis (0.3%), bladder injury (0.3%), was deferens injury (0.2%),
      iatrogenic orchiectomy (0.1%), and postoperative death. Most of them occurred in
      the early years of the clinic, and nearly one-half were technical in nature.
      Careful training, stressing the importance of gentle handling of the tissues, and
      meticulous dissection with emphasis on learning groin anatomy should reduce the
      incidence of such complications.

PMID- 9563034
TI  - Recurrent parotid abscess formation 8 years after an episode of cancrum oris.
AB  - Recurrent parotid abscess formation as a consequence of isolated right parotid
      duct osteal stenosis was a very unusual sequela of successfully treated early
      cancrum oris. Interestingly, it manifested after an uneventful interval of 8
      years and required a near-total conservative parotidectomy for cure.

PMID- 9563035
TI  - Antenatal detection of hiatus hernia.
AB  - A routine ultrasound scan in a primigravida at 29 weeks' gestation showed that
      her fetus had a fluid-filled viscus above the diaphragm in the mid-line. This was
      initially thought to be the stomach, either as part of a congenital Bochdalek
      diaphragmatic hernia or an hiatus hernia. Subsequent scans suggested that this
      was the stomach with an additional loop of bowel. After birth, laparotomy
      confirmed that the stomach had herniated into the chest through a very lax
      oesophageal hiatus. The stomach was easily reduced into the abdomen with no
      evidence to suggest a congenital short oesophagus, the crura were tightened, and
      an anterior fundoplication performed.

PMID- 9563036
TI  - Spontaneous gastrointestinal perforation in very-low-birth-weight infants--a rare
      complication in a neonatal intensive care unit.
AB  - Over a 6-year period (1989-1995), gastrointestinal (GI) perforation was diagnosed
      in nine preterm infants (mean gestational age 27 weeks, mean birth weight 872 g).
      Three presented with necrotizing enterocolitis (NEC), two with indwelling-tube
      induced perforation of the stomach, one with small-left-colon syndrome, and
      another with meconium ileus. Spontaneous intestinal perforation occurred in two
      similar very-low-birth-weight (VLBW) infants, in the distal ileum, on days 8 and
      9 of life, respectively. The only clinical sign was extensive abdominal
      distension, and abdominal X-ray studies revealed free peritoneal air. All
      findings were distinct from those associated with NEC. Their further clinical
      course was complicated by reperforation on day 32 and 39, respectively. They
      subsequently recovered and presented without GI problems at the corrected ages of
      4 and 2 months, respectively. In contrast to high mortality of 57% in the group
      with non-spontaneous intestinal perforations, spontaneous perforation seems to
      have a good prognosis even in VLBW infants if diagnosed and treated promptly.

PMID- 9563037
TI  - Progressive pan-colonic fibrosis secondary to oral administration of pancreatic
      enzymes.
AB  - Most patients with cystic fibrosis require oral administration of pancreatic
      enzymes to treat pancreatic insufficiency. Recent use of higher-strength enzyme
      preparations in large doses has been found to be associated with fibrotic
      strictures of the colon. We report a case of pancolonic fibrosis due to
      pancreatic enzyme use.

PMID- 9563038
TI  - Intra-pancreatic splenic artery pseudoaneurysm. A rare complication of chronic
      calcific pancreatitis.
AB  - The authors present the case of a 12-year-old boy with a history of chronic upper
      abdominal pain. Based on ultrasonography, endoscopic retrograde cholangio
      pancreatography, and computerized tomography, a diagnosis of chronic calcific
      pancreatitis with dilation of the main pancreatic duct and a pseudocyst of the
      proximal pancreas was made. At surgery, in addition to confirmation of the above
      findings, a pseudoaneurysm arising from the splenic artery was found in the head
      and body of the pancreas. Pancreaticoduodenal resection including the
      pseudoaneurysm was performed. Postoperatively the child developed diabetes, which
      is easily managed with small doses of insulin.

PMID- 9563039
TI  - Infantile hemangioendothelioma of the liver associated with anomalous dilated and
      tortuous vessels on the placental surface.
AB  - An unusual vascular anomaly of the placenta and infantile hemangioendothelioma
      (IH) of the liver is described. The patient was an infant with a low birth weight
      for dates whose placenta showed markedly dilated and tortuous vessels, mainly
      venous but some arterial, on the fetal surface. Only one case of such a placental
      vessel anomaly and no similar case associated with IH of liver has been described
      previously, although cutaneous hemangiomas have occasionally been reported to
      occur with IH.

PMID- 9563040
TI  - Isolated Caroli's disease presenting as an exophytic mass in the liver.
AB  - A case of isolated Caroli's disease in a 2-year-old female presented as an
      exophytic cystic mass of the liver. A palpable mass below the right costal margin
      and displacement of the right colon were the main points of clinical
      presentation. Preoperatively, sonographic signs of intraluminal vascular tracts
      were identified. At laparotomy, the mass was found at the inferior border of the
      right lobe of the liver next to the gallbladder and was easily removed by wedge
      excision. Intraoperative liver biopsies and histologic findings of the excised
      lesion confirmed the diagnosis.

PMID- 9563041
TI  - Transumbilical resection and umbilical plasty for patent omphalomesenteric duct.
AB  - This paper describes a transumbilical resection and umbilical plasty for
      treatment of a patent omphalomesenteric duct (POMD). In a newborn infant with a
      POMD, a skin incision was made circumscribing the mucocutaneous junction of the
      protruded duct. The duct was completely extirpated with a wedge resection of the
      connection to the intestine and an umbilical plasty was performed. The
      postoperative appearance was excellent. It appears that transumbilical resection
      and umbilical plasty may be a satisfactory operation for POMD.

PMID- 9563042
TI  - Ileal atresia associated with an omphalomesenteric duct remnant.
AB  - This paper describes an unusual case of ileal atresia associated with an
      omphalomesenteric duct (OMD) remnant. A 1-day-old male developed bilious vomiting
      and abdominal distension. At laparotomy, the distal portion of the ileum was
      connected to the umbilicus with a fibrous band. Around this omphalomesenteric
      band, the ileum was strangulated and necrotic; the end of the ileum was atretic.
      Apart from these structures, the cecum terminated without mesentery. This
      experience shows evidence of an OMD remnant as a possible cause of jejunoileal
      atresia.

PMID- 9563044
TI  - Abdominoscrotal hydrocoeles: little place for conservatism.
AB  - Abdominoscrotal hydrocoeles (ASH) are infrequently reported in children. The
      presence of bilateral ASH is even rarer, with fewer than five cases reported to
      date. ASH are present at birth and tend to be progressive in nature. Spontaneous
      resolution has not been documented. The pathogenesis is uncertain and their
      presence in the neonatal period suggests a preformed abnormality of the processus
      vaginalis. Diagnosis is suspected on clinical examination and confirmed by
      ultrasonography, which is a reliable diagnostic tool. Undescended testes
      frequently coexist. Early surgery is the preferred management, and complications
      are frequent if left unattended. Surgery is simply an extension of a hernia
      operation, without the need for a laparotomy.

PMID- 9563043
TI  - Laparoscopic appendectomy and duodenocolonic dissociation (LADD) procedure for
      malrotation.
AB  - The treatment of "asymptomatic" intestinal malrotation remains controversial,
      particularly beyond the neonatal period. Two cases illustrate the application of
      laparoscopy for correction of malrotation: one in an older child and another in
      an asymptomatic infant. Both patients recovered well and were discharged 2 days
      after surgery. Laparoscopic appendectomy and duodenocolonic dissociation allows
      excellent visualization of the duodenocolic and Ladd's bands and easily
      accommodates appendectomy. The availability of this minimal-access technique
      should encourage correction of malrotation in the asymptomatic patient.

PMID- 9563045
TI  - Abdominoscrotal hydrocele in infancy: a study of 15 cases.
AB  - Only 25 cases of unilateral abdominoscrotal hydrocele (ASH) and 3 of bilateral
      ASH have been reported since 1834. Fifteen infants with ASH were treated on a
      single pediatric surgery service during a period of 4 years, accounting for 1.7
      per 1,000 outpatient visits. In 4 cases the defect was bilateral. Although this
      unusual concentration of cases in unexplained, recognition and careful
      documentation of ASH in infancy is recommended.

PMID- 9563047
TI  - Congenital H-type urethroanal fistula.
AB  - A case of congenital urethroanal fistula with a normal anterior urethra in a male
      child is reported. The fistula was demonstrated between the prostatic urethra and
      anorectum. This anomaly is usually associated with an atretic anterior urethra
      and has been variously described as a variant of a urethral duplication by some
      authors, and of an anorectal malformation (ARM) by others. We conclude that its
      rightful classification is as a variant of ARM in which the fistula is a result
      of persistence of the cloacal duct and corresponds to the anorecto-vestibular
      fistula with a normal anus (perineal canal) in a female.

PMID- 9563046
TI  - Transverse colonic stenosis.
AB  - A 3-year child presented with episodic lower abdominal pain; during the eighth
      attack, a mass was palpable in the left upper quadrant, and a barium enema
      revealed a stenotic area in the transverse colon. This was resected and an
      uneventful postoperative course followed. Subsequently, the child has remained
      symptom-free. instruments are no longer in use.

PMID- 9563049
TI  - Cystic nephroma: a rare benign renal tumor.
AB  - We report two boys aged 1 year and 2 years 2 months, respectively, with cystic
      nephromas. Both presented with a painless abdominal mass. Computed tomography
      showed a homogeneous, multicystic tumor of the lower pole of the kidney in both
      cases with thin septa without solid parts. Macroscopically, the surface of the
      tumor was smooth. Both patients underwent a renal-sparing procedure; histology
      confirmed the diagnosis of cystic nephroma.

PMID- 9563048
TI  - Laparoscopic removal of an autoamputated ovarian cyst in an infant.
AB  - Ovarian cysts autoamputation is an extremely rare complication. All reported
      cases were removed by laparotomy. A successful laparoscopic removal is presented.

PMID- 9563050
TI  - Acute renal failure in bilateral urinary tract tuberculosis.
AB  - A case of bilateral urinary tract tuberculosis presenting with acute renal
      failure is reported. It is believed to be the first reported instance of the
      disease presenting in this form. The patient was managed with preliminary high
      diversion followed by bilateral replacement of the ureters with ileal loops that
      were anastomosed end-to-side and then implanted into the bladder.

PMID- 9563051
TI  - Giant ureteral stone in a 4-year-old boy.
AB  - A 4-year-old boy presented with sudden onset of fever, pyuria, and bacteriuria.
      Ultrasound revealed left hydronephrosis and hydroureter. A plain abdominal
      radiography and excretory urogram showed a giant ureteral stone measuring 9 cm
      causing ureteral obstruction. Underlying anatomic or metabolic abnormalities were
      not detected. Extraction of the stone resulted in complete disappearance of the
      hydronephrosis and hydroureter.

PMID- 9563052
TI  - Intra-abdominal testis with mature teratoma.
AB  - Tumors in an undescended testis are rare in children. We report a mature teratoma
      arising in the intra-abdominal testis (IAT) of a 1-year-old boy. Preoperative
      laparoscopy revealed a right IAT near the inguinal ring. As the right testis
      exposed through the inguinal incision seemed to be a neoplastic mass, an
      orchidectomy was performed. Histologic examination disclosed a mature teratoma.
      This is a review of seven cases (including the present one) of a prepubertal
      tumor originating in an IAT. We speculate that the undescended testes did not
      cause the neoplasia, but were induced by it.

PMID- 9563053
TI  - Venous graft repair following brachial artery thrombosis in a neonate.
AB  - A case of venous graft repair to recover blood flow of a newborn's upper
      extremity, is described. Even though this complication remains uncommon, we
      emphasize on to avoid brachial artery for vascular monitorization and to perform
      microsurgical revision as elective procedure if conservative therapy is
      unsuccessful.

PMID- 9563054
TI  - Lymphangioma circumscriptum.
AB  - Two children with lymphangioma circumscriptum (LC), a rare cutaneous
      lymphangioma, are described. One was diagnosed antenatally as having a right
      axillary cystic hygroma; in addition, postnatally LC was noted on the right
      forearm. A few years later a mediastinal lymphangioma was diagnosed. This
      combination of LC associated with additional malformations of the lymphatic
      system has not been reported previously, and may point to a generalized
      developmental disorder of the lymphatic system. The pathophysiology of the lesion
      is discussed with a review of the pertinent literature. It appears that LC
      primarily affects the subcutaneous tissue in the form of cystic dilatation of
      lymphatic channels without systemic lymphatic communication. The skin lesions are
      probably secondary to the increased intraluminal pressure. The typical clinical
      appearance is manifested by multiple skin vesicles and lymphorrhea. The main
      treatment modality is surgical excision. Recurrences are not unusual and require
      re-excision.

PMID- 9563055
TI  - Congenital hemangiopericytoma: two case reports.
AB  - Congenital hemangiopericytoma is a rare tumor consisting of capillaries
      surrounded by pericytes. Only histologically can the tumor be distinguished from
      other vascular hamartomas. For a long time the congenital type was considered
      benign; however, metastases have recently been described. A histologic diagnosis
      of all soft-tissue sarcomas should be made. We describe two patients with
      congenital hemangiopericytomas in whom the diagnosis was not suspected until
      after histologic examination. Long-term follow-up is indicated.

PMID- 9563056
TI  - Benign lipoblastoma arising in the neck.
AB  - Lipoblastoma and lipoblastomatosis are rare benign tumours of embryonal fat that
      exhibit a tendency to invade locally but not to metastasize. This condition most
      often presents before the age of 3 years, affects males more than females, and is
      typified by a slowly-growing, usually subcutaneous mass arising in a limb. Cases
      involving the head and neck are extremely rare, with only nine cases in the neck
      having been described to date. This tenth case arose in a 13-month-old male
      presenting with a rapidly enlarging lump in the right side of the neck,
      clinically mimicking a cystic hygroma. Diagnosis is by histology, and treatment
      involves complete surgical resection. We report this tenth known case of
      lipoblastoma in the neck and review the literature.

PMID- 9563057
TI  - Prenatally detected cystic neuroblastoma.
AB  - A case of adrenal cystic neuroblastoma (NB) detected by prenatal ultrasonography
      (US) is presented. The suprarenal mass initially showed pure cystic features on a
      variety of imaging studies such as US, computed tomography, and magnetic
      resonance imaging. Tumor markers were negative. The mass was suspected to be an
      adrenal hemorrhage rather than a NB. Three months later, although the diameter
      was unchanged, the thickness of the cyst wall seemed to have slightly increased.
      Surgical exploration revealed an adrenal cystic tumor and histology showed a NB
      in situ. Forty-five infants with prenatally detected NB were found in the English
      literature; about one-half of them were cystic NBs, and most had a favorable
      outcome.

PMID- 9563058
TI  - Mediastinal lipoma in children.
AB  - Mediastinal masses are uncommonly encountered in childhood. These tumours are
      often interesting because of the varied mediastinal tissues from which they
      arise. Despite extensive investigations, a large percentage of these lesions
      remain undiagnosed prior to operation. We describe two rare cases of mediastinal
      lipoma. The first was incidentally diagnosed whereas the second patient presented
      with respiratory symptoms. The definitive diagnosis was established at surgery,
      which was curative.

PMID- 9563059
TI  - Sutureless "button and hole" splenopexy.
AB  - A new technique for fixation of a mobile spleen is described. It offers the
      advantages of a minimally risky procedure that very effectively keeps a mobile
      spleen in its bed without foreign materials and is feasible even when the
      gastrosplenic ligament is absent and the splenic vessels are uncovered. Our
      "button and hole" sutureless splenopexy was performed in six patients from 1979
      to 1995. Three had a gastric volvulus (GV) and an extremely mobile spleen; one of
      these also had a diaphragmatic eventration. Another three had torsion of the
      spleen; in one it occurred 9 months after repair of a diaphragmatic hernia. We
      achieved good results with splenopexy as the sole operation in two cases where a
      wandering spleen produced a GV.

PMID- 9563060
TI  - Manual reduction with the index finger for infantile intussusception. A
      modification of Hutchinson's maneuver.
AB  - Manual reduction with the index finger (modified Hutchinson's maneuver) enabling
      simple and safe manual reduction of infantile intussusception is described. The
      procedure was used in four patients, two boys and two girls, ranging in age from
      2 to 15 months, as greater than normal compression was necessary and/or serosal
      splitting occurred during conventional reduction. The technique is as follows: in
      addition to the proximal bowel compression with Hutchinson's maneuver, the
      surgeon inserts his index finger into the intussusceptum via its neck. The finger
      enables the surgeon to sound a wider space between the intussusceptum and
      intussuscipiens, which is most likely to be responsive to bowel compression.
      Although the intussusceptions in the four patients were categorized as ileo-ileo
      colic (three cases) and ileo-ileal (one case) types, this manual reduction
      technique was successful in all cases, no bowel rupture occurred, and
      hospitalization was no longer than with the conventional procedure. We conclude
      that this modified Hutchinson's maneuver may contribute to successful surgical
      reduction of infantile intussusception.

PMID- 9563061
TI  - Management of multiple intestinal atresias and perforation with intraluminal
      stenting.
AB  - Intraluminal stenting of the gastrointestinal (GI) tract in both multiple
      intestinal atresias and perforations was used in three patients. In the atresia
      patients (2), a piercing trocar was used to create continuity of the GI tract and
      as a guide to thread the intestine over the stent. All patients currently
      demonstrate normal growth and development on routine enteral feeds. None
      developed anastomotic leaks or strictures.

PMID- 9563062
TI  - Aspiration of pins.

PMID- 9563063
TI  - An interview with a distinguished pharmaceutical scientist.

PMID- 9563064
TI  - Recent advances in structure-based ligand design using molecular dynamics and
      Monte Carlo methods.

PMID- 9563065
TI  - Drug exsorption from blood into the gastrointestinal tract.
AB  - Drugs are exsorbed from the blood across the gastrointestinal membranes by
      passive or active processes. In the case of a passive transport mechanism, the
      exsorption of drugs depends on the concentration gradients between the serosal
      and mucosal sides. The extent of secretion (exsorption) is determined by numerous
      factors such as extent of binding to serum proteins, distribution volume,
      lipophilicity, pKa and molecular size of drugs, and the blood flow rate in the
      gut. Specific transport systems such as P-glycoprotein (P-gp), organic cation and
      organic anion transporters are found to be involved in active intestinal
      secretion of drugs. Intestinal secretory transport systems reduce the extent of
      drug absorption sometimes resulting in low oral bioavailability. It is,
      therefore, important to know whether poor drug absorption is due to the
      involvement of specialized secretory transport systems. Modulation of intestinal
      secretory transport can be a means to enhance absorption of drugs with low oral
      bioavailability if exsorption of drugs is based on active secretion pathways that
      are open for control from the "outside".

PMID- 9563066
TI  - Localized delivery of proteins in the brain: can transport be customized?
AB  - Certain central nervous system (CNS) diseases are characterized by the
      degeneration of specific cell populations. One strategy for treating
      neurodegenerative diseases is long-term, controlled delivery of proteins such as
      epidermal growth factor (EGF) and nerve growth factor (NGF). Since proteins
      permeate through brain capillaries very slowly, local administration using
      polymeric implants, continuous infusion pumps, or transplanted, protein-secreting
      cells may be required to achieve therapeutic concentrations in the tissue. The
      efficiency of local distribution, and hence effectiveness of local therapy,
      depends on the rate of protein migration through tissue. The rate of dispersion
      of molecules in a quiescent, isotropic medium can be characterized by the
      molecular diffusion coefficient, D, which can be measured by techniques such as
      quantitative autoradiography, iontophoresis, and fluorescence photobleaching
      recovery (FPR). These methods are reviewed, with an emphasis on their application
      to measurement of D for proteins in the brain. Biophysical techniques yield
      quantitative descriptions of local protein distribution and may enable
      discrimination of mechanisms of protein transport in the brain. This capability
      suggests a new paradigm for design of protein therapies, in which proteins and
      delivery systems are collectively customized to provide sustained protein
      availability over predetermined volumes of tissue.

PMID- 9563067
TI  - Advances and challenges in the prevention and treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia and accounts for
      one-half to three-fourths of all cases of dementia. In the United States, AD is
      the leading cause of a loss of independent living and subsequent
      institutionalization. Approximately 4 million Americans are currently diagnosed
      with Alzheimer's disease-which results in greater than $100 billion dollars in
      health care costs. This review provides a description of the cognitive and
      neuropathological features of AD and the challenge that aging populations around
      the globe pose to health care systems and to societies. A review of new and
      promising therapeutic strategies for the prevention of AD is discussed which
      includes estrogen replacement therapy and anti-inflammatory therapeutics.
      Pharmaceutical approaches that delay the progression of the disease, such as
      antioxidants, are discussed as well as therapeutic strategies for improvement of
      cognitive function in AD patients, including the new generation of compounds
      aimed at enhancing cholinergic function. This section is followed by a review of
      the current status on nerve growth factor trials. The final section addresses the
      issue of the genetic linkages of AD, the impact of transgenic and gene knockout
      mouse models of AD on research in the field and the potential use of gene therapy
      to treat AD.

PMID- 9563069
TI  - Coverage and precision of confidence intervals for area under the curve using
      parametric and non-parametric methods in a toxicokinetic experimental design.
AB  - PURPOSE: The coverage and precision of parametric Bailer-type confidence
      intervals (CIs) for area under the curve (AUC) was compared to nonparametric
      bootstrap confidence intervals. METHODS: Concentration-time data was simulated
      using Monte Carlo simulation under a toxicokinetic paradigm with sparse (SSC) and
      dense sampling (DSC) conditions. AUC was calculated using the trapezoidal rule
      and 95% CIs were computed using various parametric and nonparametric methods.
      RESULTS: Under SSC, the various parametric CIs contained the true population AUC
      with coverage probabilities ranging from 0.77 to 0.95 with low inter-subject
      variation (coefficient of variation (CV) = 15%) and from 0.82 to 0.95 with high
      inter-subject variation (CV = 50%). The nominal value should be close to 0.95.
      DSC tended to increase coverage by about 0.05. Bailer's method always produced
      the lowest coverage of all parametric CIs examined. Under SSC, bootstrap CIs had
      coverage probabilities ranging from 0.62 (CV = 15%) to 0.68 (CV = 50%). DSC
      increased coverage to 0.77. Parametric CIs were wider than their nonparametric
      counterparts, often giving lower CI estimates less than zero. Bailer's method and
      Bailer's method using the jackknife estimate of the standard error were the worst
      in this respect. Bootstrap CIs never had lower CI estimates less than zero.
      However, SSC tends to produce bootstrap distributions that are not continuous
      which, if used, may produce biased CI estimates. CONCLUSIONS: Bootstrap CI
      estimates were judged to be the "best". However, the limitations of the bootstrap
      should be clearly recognized and it should not be used indiscriminately.
      Examination of the bootstrap distribution for its degree of discreteness must be
      part of the statistical process.

PMID- 9563068
TI  - The duration of measuring partial AUCs for the assessment of bioequivalence.
AB  - PURPOSE: To determine favourable sampling conditions for assessing bioequivalence
      by the comparison of partial AUCs in the early phase of concentration-time
      profiles. METHODS: Two-period crossover trials were simulated. They assumed a
      wide range of the ratios of absorption rate constants of the test (T) and
      reference (R) formulations (kaT/kaR). Averages and standard deviations of the
      corresponding ratios of simulated partial AUCs (AUCpT/AUCpR) were determined
      together with the statistical power of assessing bioequivalence, i.e., the
      percentage of simulated trials in which bioequivalence was declared. RESULTS: The
      power for stating bioequivalence was high when AUCp was recorded until the
      earlier rather than the later of two peaks in each subject. Similarly, power was
      comparatively high when AUCp was measured until the time of the reference peak
      instead of multiples of this time. Power was high also when AUCp was determined
      until the fixed true, population mean time of the reference formulation instead
      of multiples of this time. The pattern for the kinetic sensitivity parallelled
      that found for the power, while the standard deviations changed generally in the
      opposite direction. CONCLUSIONS: The effectiveness (power) of evaluating
      bioequivalence in the early phase of concentration-time profiles by partial AUCs
      generally decreases when the duration for measuring the metric is extended. Among
      the investigated designs, determination of partial AUCs until the earlier of two
      peaks in each subject is the most powerful.

PMID- 9563070
TI  - Possible role of anion exchanger AE2 as the intestinal monocarboxylic acid/anion
      antiporter.
AB  - PURPOSE: The purpose of the present study was to investigate the transport of
      organic monocarboxylic acids mediated by the anion exchanger AE2, which has been
      already reported to be present at several tissue cell membranes, including
      intestinal brush border membrane in rabbit. METHODS: Membrane transport of
      organic monocarboxylic acids by AE2 was investigated by transient AE2-gene
      expression in HEK 293 cells and subsequent uptake studies by the cells. RESULTS:
      Functional transfection of AE2 was confirmed by the enhanced 36Cl- efflux from
      the cells. When preloaded with chloride anion. AE2-transfected cells demonstrated
      a significantly enhanced [14C]benzoic acid transport activity compared with mock
      transfected cells. The AE2-mediated uptake was saturable with kinetic parameters
      of Km = 0.26 +/- 0.08 mM and Vmax = 6.14 +/- 0.52 nmol/mg protein/3 min and the
      uptake of [14C]benzoic acid was pH-dependent with a maximal uptake at pH 6.5. AE2
      mediated [14C]benzoic acid uptake was inhibited by Cl-, HCO3-, and DIDS. AE2
      transfected cells demonstrated significantly enhanced transport activity for
      nicotinic acid, propionic acid, butyric acid, and valproic acid as well as
      benzoic acid compared with mock-transfected cells. CONCLUSIONS: AE2 is
      functionally involved in the anion antiport for organic monocarboxylic acids as
      well as inorganic anions and is supposed to play a partial role in the intestinal
      transport of organic acids.

PMID- 9563071
TI  - The use of pharmacoscintigraphy to elucidate food effects observed with a novel
      protease inhibitor (saquinavir).
AB  - PURPOSE: To evaluate mechanistically the effect of food on the absorption and
      gastrointestinal transit of the protease inhibitor saquinavir. METHODS:
      Pharmacoscintigraphic investigation in eight healthy volunteers. RESULTS: Gastric
      emptying occurred rapidly in the fasted state with some capsules leaving the
      stomach prior to disintegration. Unmeasurable plasma concentrations were observed
      in several subjects when dosed under fasted conditions. Following post-prandial
      administration the radioactive marker became re-distributed within the stomach
      contents and consequently slower gastric emptying resulted. Plasma concentrations
      under fed conditions were measurable up to 12 hrs after administration in seven
      of the eight subjects. Six of the eight plasma profiles showed secondary peaks at
      c. 4 hours post-dose; two of which coincided with the gastrocolonic response
      following ingestion of lunch. CONCLUSIONS: Bioavailability of saquinavir is
      significantly improved in the presence of food. Emptying of intact capsules in
      the fasted state may further reduce bioavailability. In the fed state, capsules
      disintegrate rapidly and gastric emptying is prolonged which may improve exposure
      of the drug to target absorption sites. Saquinavir may be absorbed from the
      colon. Second peaks in the absorption profile can only be attributed to
      gastrocolonic response following ingestion of a meal in some cases. Increased
      absorption is more likely to be due to an increase in dissolved drug being
      available for absorption due to general increased motility and secretion
      stimulated by ingestion of a meal.

PMID- 9563072
TI  - Active apical secretory efflux of the HIV protease inhibitors saquinavir and
      ritonavir in Caco-2 cell monolayers.
AB  - PURPOSE: To investigate in vitro the mechanisms involved in the gastro-intestinal
      absorption of the HIV protease inhibitor, saquinavir mesylate (Invirase), whose
      oral bioavailability is low, variable, and significantly increased by co
      administration with ritonavir, also an HIV protease inhibitor but with higher
      oral bioavailability. METHODS: Confluent epithelial layers of human Caco-2 cells
      mimicking the intestinal barrier. RESULTS: Both saquinavir and ritonavir showed
      polarized transport through Caco-2 cell monolayers in the basolateral to apical
      direction (secretory pathway), exceeding apical to basolateral transport
      (absorptive pathway) by factors of 50-70 and 15-25, respectively. Active efflux
      was temperature dependent, saturable and inhibited by verapamil and cyclosporin
      A. Saquinavir and ritonavir decreased each other's secretory permeability and
      hence elevated their net transport by the absorptive pathway. CONCLUSIONS:
      Saquinavir and ritonavir are both substrates for an efflux mechanism in the gut,
      most likely P-glycoprotein, which acts as a counter-transporter for both drugs.
      Together with sensitivity to gutwall metabolism by cytochrome P-450 3A, this may
      partially account for the low and variable oral bioavailability of saquinavir in
      clinical studies and for its increased bioavailability after co-administration
      with ritonavir.

PMID- 9563073
TI  - Mechanism of compound- and species-specific food effects of structurally related
      antiarrhythmic drugs, disopyramide and bidisomide.
AB  - PURPOSE: To determine mechanism of food effects observed with bidisomide but not
      with the structurally similar drug, disopyramide. METHODS: Food effect studies of
      bidisomide and disopyramide were conducted with and without a standardized high
      fat meal in healthy subjects and in the dog. Intestinal metabolism of
      disopyramide and absorption of the metabolites were examined after oral
      administration of the drug to the dogs with portal vein canula implanted. Effects
      of food or a mixture of amino acids on metabolism of [14C]disopyramide were
      examined after intraportal infusion of the drug with and without high fat meal
      and after drug infusion into portal vein with the amino acid mixture,
      respectively. RESULTS: The systemic availability of bidisomide was markedly
      reduced with food in humans, whereas the systemic availability of disopyramide
      did not change notably. In the dog, the systemic availability of bidisomide was
      also reduced with food. The systemic availability of disopyramide did not change
      with food. This was due to the fact that reduction in absorption was compensated
      by reduction of metabolism. There was no evidence for reduction in hepatic and
      intestinal metabolism with food. CONCLUSIONS: The apparent reduction in
      disopyramide metabolism with food may be due to an increase in colonal and/or
      lymphatic absorption. Food effects on the apparent systemic availability of
      bidisomide and disopyramide in the dog were similar to those in the rat. However,
      there was substantial species difference in the mechanism of food effects.

PMID- 9563074
TI  - Stability of alkoxycarbonylamidine prodrugs.
AB  - PURPOSE: Alkoxycarbonylamidine prodrug modification was used to mask the
      positively-charged amidine moiety of an Arg-Gly-Asp peptidomimetic and enhance
      oral bioavailability. The aqueous stability of ethoxycarbonylamidine (ECA),
      ethanethiocarbonylamidine (ETCA) and phenoxycarbonylamidine (PCA) prodrugs was
      examined. METHODS: Degradation was followed by RP-HPLC and rate constants were
      determined from a degradation scheme defined by product analysis. RESULTS: ECA
      gave a pH of maximum stability at pH approximately 7 and was independent of pH
      below pH approximately 4. A novel degradation pathway of ECA, conversion to
      ethoxycarbonyl- aminocarbonyl, was observed below pH 7. The relative rates below
      pH 7 were ECA approximately ETCA < PCA, in the same order of decreasing pKa of
      the conjugate acid of the substituted amidino group. Base-catalyzed cleavage of
      ECA to yield the amidine derivative gave the relative rates ECA < ETCA < PCA, in
      agreement with the decreasing pKa of the leaving groups. CONCLUSIONS: The
      observed rate constants at all pHs were small enough that only 5-30% (depending
      on the substituent) undesirable degradation is predicted during transit time of
      the gut. The spontaneous post-absorptive conversion to the amidine drugs at
      neutral pH is predicted to be 6x greater for the PCA than the ECA prodrugs.

PMID- 9563075
TI  - Influence of different fat emulsion-based intravenous formulations on the
      pharmacokinetics and pharmacodynamics of propofol.
AB  - PURPOSE: The influence of different intravenous formulations on the
      pharmacokinetics and pharmacodynamics of propofol was investigated using the
      effect on the EEG (11.5-30 Hz) as pharmacodynamic endpoint. METHODS: Propofol was
      administered as an intravenous bolus infusion (30 mg/kg in 5 min) or as a
      continuous infusion (150 mg/kg in 5 hours) in chronically instrumented male rats.
      Propofol was formulated as a 1% emulsion in an Intralipid 10%-like fat emulsion
      (Diprivan-10, D) or as a 1%- or 6% emulsion in Lipofundin MCT/LCT-10% (P1% and
      P6%, respectively). EEG was recorded continuously and arterial blood samples were
      collected serially for the determination of propofol concentrations using HPLC.
      RESULTS: Following bolus infusion, the pharmacokinetics of the various propofol
      emulsions could adequately be described by a two-compartmental pharmacokinetic
      model. The average values for clearance (Cl), volume of distribution at steady
      state (Vd,ss) and terminal half-life (t1/2, lambda 2) were 107 +/- 4 ml/min/kg,
      1.38 +/- 0.06 l/kg and 16 +/- 1 min, respectively (mean +/- S.E. n = 22). No
      significant differences were observed between the three propofol formulations.
      After continuous infusion these values were 112 +/- 11 ml/min/kg, 5.19 +/- 0.41
      l/kg and 45 +/- 3 min, respectively (mean +/- S.E., n = 20) with again no
      statistically significant differences between the three propofol formulations.
      Comparison between the bolus- and the continuous infusion revealed a
      statistically significant difference for both Vd,ss and t1/2, lambda 2 (p <
      0.05), whereas Cl remained unchanged. In all treatment groups infusion of
      propofol resulted in a burst-suppression type of EEG. A profound hysteresis loop
      was observed between blood concentrations and EEG effect for all formulations.
      The hysteresis was minimized by a semi-parametric method and resulted in a
      biphasic concentration-effect relationship of propofol that was described non
      parametrically. For P6% a larger rate constant onset of drug effect (t1/2,keo)
      was observed compared to the other propofol formulations (p < 0.05). CONCLUSIONS:
      The pharmacokinetics and pharmacodynamics of propofol are not affected by to a
      large extent the type of emulsion nor by the concentration of propofol in the
      intravenous formulation.

PMID- 9563076
TI  - Species differences of serum albumins: II. Chemical and thermal stability.
AB  - PURPOSE: The chemical and thermal stability of five species of mammalian serum
      albumins (human, bovine, dog, rabbit, and rat) were investigated, and
      conformational stabilities were compared to obtain structural information about
      the different albumins. METHODS: The chemical stability was estimated by using
      guanidine hydrochloride (GdnCl), and monitored by fluorometry and circular
      dichroism (CD). Thermal stability was evaluated by differential scanning
      calorimetry (DSC). RESULTS: In human, bovine, and rat albumin, two transitions
      were observed when GdnCl-induced denaturation was monitored fluorometrically,
      indicating at least one stable intermediate, although, in dog and rabbit albumin,
      only one transition was observed. However, GdnCl denaturation, as monitored by
      the ellipticity, showed a two-state transition in all species used in this study.
      Since these proteins, showing two transitions, contained a conserved tryptophan
      residue within domain II, these structural changes might have occurred in domain
      II during intermediate formation. DSC measurements showed that human, bovine, and
      rat albumin exhibited single sharp endotherms and these were clearly consistent
      with a two-state transition, while the deconvolution analysis of broad
      thermograms observed for dog and rabbit albumin showed that the absorption peaks
      could be approximated by a two-component composition, and were consistent with
      independent transitions of two different cooperative blocks. CONCLUSIONS: These
      experimental results demonstrate that species differences exist with respect to
      the conformational stability and the mechanism of the unfolding pathway for
      mammalian albumin.

PMID- 9563077
TI  - Inhibition of tracheal vascular extravasation by liposome-encapsulated albuterol
      in rats.
AB  - PURPOSE: To develop a liposome-based system for systemic delivery of anti
      inflammatory drugs to airways and other inflamed tissues. METHODS: Postcapillary
      venular gap junctions open during airway inflammation and allow fluid
      accumulation and permit molecules (e.g. complement, kininogen) to enter tissues,
      initiating inflammatory cascades. Beta-adrenergic agonists prevent inflammatory
      plasma extravasation, but because of their deleterious side effects, they are not
      used intravenously. When sterically stabilized "stealth" liposomes are injected
      i.v., they remain in the circulation for long periods. Inflammatory mediators
      [e.g., substance P(SP)] open postcapillary venular gaps and allow liposomes and
      their contents to be deposited selectively in the inflamed tissue. RESULTS: We
      hypothesized that liposomes encapsulating a beta-adrenergic agonist, such as
      albuterol, would deposit selectively in inflamed airway tissue, where the drug
      would slowly leak out of the liposomes, resulting in closure of the gaps, thus
      preventing subsequent inflammatory extravasation. To test this hypothesis, we
      delivered albuterol-loaded liposomes i.v. in rats. Then we injected SP to open
      the venular gaps and allow accumulation of the drug-loaded liposomes in airway
      tissue. We examined whether this treatment resulted in inhibition of subsequent
      plasma extravasation induced by SP. The results indicate that liposome
      encapsulated albuterol inhibits subsequent extravasation, presumably by leaking
      out of liposomes in airway tissue. This inhibition occurs for prolonged periods
      of time and with limited side effects compared to the effect of free albuterol.
      CONCLUSIONS: We conclude that liposomes loaded with appropriate drugs, by
      migrating to inflamed tissue and subsequently inhibiting inflammatory cascades,
      may be of therapeutic value in inflammatory diseases.

PMID- 9563078
TI  - Effect of dose and release rate on pulmonary targeting of liposomal triamcinolone
      acetonide phosphate.
AB  - PURPOSE: To demonstrate the importance of dose and drug release rate for
      pulmonary targeting of inhaled glucocorticoids using an animal model of
      intrapulmonary drug deposition. METHODS: Liposomes composed of 1,2-distearoyl
      phosphatidylcholine (DSPC), 1,2-distearoyl phosphatidylglycerol (DSPG) and
      triamcinolone acetonide phosphate (TAP) or liposomes containing triamcinolone
      acetonide (TA) were prepared by a mechanical dispersion method followed by
      extrusion through polycarbonate membranes. Encapsulation efficiency was assessed
      after size exclusion gel chromatography by reverse phase HPLC. The effect of
      liposome size (200 nm and 800 nm) on the release kinetics of water-soluble
      encapsulated material was determined in vitro at 37 degrees C using 6
      carboxyfluorescein as a marker and Triton X-100 (0.03%) as a leakage inducer. To
      investigate the relationship between drug release and pulmonary targeting, 100
      micrograms/kg of TAP in 800 nm liposomes was delivered to male rats by
      intratracheal instillation (IT) and the results compared to data for 100
      micrograms/kg TA liposomes (recently shown to exhibit a rapid drug release under
      sink conditions) and to previous studies reported for an equal dose of TAP in
      solution and TAP in 200 nm (1). Pulmonary targeting was assessed by
      simultaneously monitoring glucocorticoid receptor occupancy over time in lung and
      liver using an ex vivo receptor binding assay as a pharmacodynamic measure of
      glucocorticoid action. To assess the effect of dose on pulmonary targeting
      experiments were performed using 2.5, 7.5, 25, 100, and 450 micrograms/kg of TAP
      in 800 nm liposomes. RESULTS: The in vitro efflux of 6-carboxyfluorescein from
      (DSPC:DSPG) liposomes after exposure to Triton-X was biexponential. The terminal
      half-lives of 3.7 h and 9.0 h for the 200 nm and 800 nm liposomes, respectively,
      demonstrated that larger liposomes promote slower release of encapsulated water
      soluble solute while previous results already indicated that encapsulation of
      lipophilic TA does not result in sustained release. Pulmonary targeting, defined
      as the difference between cumulative lin and liver receptor occupancies was most
      pronounced for the 800 nm liposomes (370%xh), followed by the 200 nm preparation
      (150%xh). No targeting was observed for TAP in solution (30%xh) or the rapid
      releasing TA liposome preparation. Correspondingly, the mean pulmonary effect
      time (MET) increased from 2.4-3.0 hr for TA liposomes or TAO in solution to 5.7 h
      and > 6.2 h for TAP in 200 nm and in 800 nm liposomes, respectively. Escalating
      doses of TAP encapsulated in 800 nm liposomes revealed a distinct bell shaped
      relationship between the TAP dose and pulmonary targeting with a maximum
      occurring at 100 micrograms/kg (370%xh). CONCLUSIONS: The in vivo data presented
      here confirm that pulmonary residence time and dose affect the extent of lung
      targeting of glucocorticoids delivered via the lung.

PMID- 9563079
TI  - Development and internal validation of an in vitro-in vivo correlation for a
      hydrophilic metoprolol tartrate extended release tablet formulation.
AB  - PURPOSE: To develop and validate internally an in vitro-in vivo correlation
      (IVIVC) for a hydrophilic matrix extended release metoprolol tablet. METHODS: In
      vitro dissolution of the metoprolol tablets was examined using the following
      methods: Apparatus II, pH 1.2 & 6.8 at 50 rpm and Apparatus I, pH 6.8, at 100 and
      150 rpm. Seven healthy subjects received three metoprolol formulations (100 mg):
      slow, moderate, fast releasing and an oral solution (50 mg). Serial blood samples
      were collected over 48 hours and analyzed by a validated HPLC assay using
      fluorescence detection. The f2 metric (similarity factor) was used to analyze the
      dissolution data. Correlation models were developed using pooled fraction
      dissolved (FRD) and fraction absorbed (FRA) data from various combinations of the
      formulations. Predicted metoprolol concentrations were obtained by convolution of
      the in vivo dissolution rates. Prediction errors were estimated for Cmax and AUC
      to determine the validity of the correlation. RESULTS: Apparatus I operated at
      150 rpm, and pH of 6.8 was found to be the most discriminating dissolution
      method. There was a significant linear relationship between FRD and FRA when
      using either two or three of the formulations. An average percent prediction
      error for Cmax and AUC for all formulations of less than 10% was found for all
      IVIVC models. CONCLUSIONS: The relatively low prediction errors for Cmax and AUC
      observed strongly suggest that the metoprolol IVIVC models are valid. The average
      percent prediction error of less than 10% indicates that the correlation is
      predictive and allows the associated dissolution data to be used as a surrogate
      for bioavailability studies.

PMID- 9563080
TI  - Pulsatile drug release from an insoluble capsule body controlled by an erodible
      plug.
AB  - PURPOSE: The objective of this study was to develop and evaluate a pulsatile drug
      delivery system based on an impermeable capsule body filled with drug and an
      erodible plug placed in the opening of the capsule body. METHODS: The erodible
      plugs were either prepared by direct compression followed by placing the tablets
      in the capsule opening or by congealing a meltable plug material directly within
      the capsule opening. The disintegration/erosion properties of these plugs were
      determined and optimized for the final delivery system. In order to assure rapid
      drug release of the capsule content after erosion of the plug, various excipients
      (fillers, effervescent agents) and drugs with different solubilities were
      evaluated. The lag time prior to drug release and the subsequent drug release
      were investigated as function of capsule content, plug composition, plug
      preparation technique, plug hardness, weight, and thickness. RESULTS: The erosion
      time of the compressed plugs increased with increasing molecular weight of the
      hydrophilic polymer (e.g. hydroxypropyl methylcellulose, polyethylene oxide),
      decreasing filler (lactose) content and decreased with congealable lipidic plugs
      with increasing HLB-value and inclusion on surfactants. For complete and rapid
      release of the drug from the capsule body, effervescent agents had to be included
      in the capsule content. The drug delivery system showed typical pulsatile release
      profiles with a lag time followed by a rapid release phase. The lag time prior to
      the pulsatile drug release correlated well with the erosion properties of the
      plugs and, besides the composition of the plug, could be controlled by the
      thickness (weight) of the plug. CONCLUSIONS: A single-unit, capsular-shaped
      pulsatile drug delivery system was developed wherein the pulsatile release was
      controlled by the erosion properties of a compressed or congealed plug placed
      within the opening of the capsule opening.

PMID- 9563081
TI  - Controlled release gel of ibuprofen and lidocaine in epidural use--analgesia and
      systemic absorption in pigs.
AB  - PURPOSE: Reduction of the frequency of injections and localization of the
      absorption of drug molecules to the injection site would be of great advantage in
      epidural pain treatment. The epidural use of a controlled release gel of
      lidocaine and ibuprofen was studied. METHODS: The effect of a poloxamer gel (25%)
      containing 2% lidocaine.HCl and 2% ibuprofen.Na on the duration of analgesia
      after epidural administration to pigs was compared with drug in solution.
      Analgesia was assessed by observing the motor function and the nociceptive reflex
      withdrawal response to painful pressure stimulation on the feet. Pharmacokinetic
      and histological examinations were performed. RESULTS: Analgesia lasted
      significantly longer after epidural lidocaine gel injection in comparison with
      the solution. The gel prolonged the systemic absorption, thereby increasing the
      epidural availability of lidocaine for spinal analgesia. Although the absorption
      of ibuprofen was prolonged after epidural gel injection, the duration of
      analgesia as compared with the solution was not prolonged. After epidural
      injection, only slight inflammatory changes were observed in the tissue
      structures of the epidural space, but none in the spinal cord. CONCLUSIONS: These
      results demonstrate poloxamer gel to be a promising controlled-release,
      injectable epidural formulation for the management of pain.

PMID- 9563082
TI  - Pharmacokinetics of cocaine and metabolites following intragastric administration
      to ten-day-old rat pups.

PMID- 9563083
TI  - Stratum corneum thickness and apparent water diffusivity: facile and noninvasive
      quantitation in vivo.

PMID- 9563084
TI  - Lipid extracting effect on ethanol on keratinized oral mucosa.

PMID- 9563086
TI  - Modeling mucoadhesion by use of surface energy terms obtained by the Lewis acid
      Lewis base approach: III. An interaction between Teflon and carbopol.

PMID- 9563085
TI  - Negative correlation of n-octanol/water partition coefficient and transport of
      some guanine derivatives through rat jejunum in vitro.

PMID- 9563088
TI  - [Atypical benign partial epilepsy of childhood. Clinical follow-up EEG study of 3
      patients].
AB  - INTRODUCTION AND MATERIAL: Between 369 cases of benign partial epilepsy of the
      childhood with Rolandic spikes (BECRS) diagnosed in our hospital, we have been
      able to study three patients that have presented a neurophysiological and
      clinical presentation that was compatible with the form described by Aicardi and
      Chevrie in 1982. RESULTS: None of our patients had familial epilepsy precedents.
      There were no pathological birth or previous neurological disorders. The
      neurophysiological development was normal until the beginning of the clinical
      picture. The seizures began when the patients were 3 years and 4 months, and 5
      years, with partial seizures of the same characteristic that present patients
      with BECRS. Two of them had generalized tonic-clonic seizures during sleep. All
      the patients presented throughout the evolution absences myoclonic and/or atonic
      seizures. The awake EEG patterns showed normal background activity and paroxysms
      of focal spike were complexes with diffusion to central areas. During the slow
      wave sleep, every cases showed paroxysms of diffuse and generalized slow spike
      and wave complexes practically continuous. The partial seizures were scarce, but
      the absences and the atonicas seizures presented several times every day, and in
      one case appeared in the form of a grand mal state. CONCLUSIONS: The evolution of
      the patients was favourable, as they were free of seizures, with a normal
      neurophysiological development. At the beginning, the seizures were resistant to
      treatment with several antiepileptics drugs (AED). The treatment with valproic
      acid (VPA) and clonazepam (CZP), has been very effective.

PMID- 9563087
TI  - Methods development for epidemiologic investigations of the health effects of
      prolonged ozone exposure. Part I: Variability of pulmonary function measures.
AB  - The acute and subacute effects of ambient concentrations of ozone on lung
      function have been studied extensively in a variety of settings. Such studies
      generally have focused on measures of function that reflect either lung volumes
      or flows that are influenced by the physiology of large and small airways (e.g.,
      forced expiratory volume in one second [FEV1). Data from animal studies suggest
      that the effects of prolonged exposure to elevated ambient concentrations of
      ozone result in abnormalities in the centriacinar region of the lung; and
      dosimetry models for humans predict that long-term exposure to ozone could impact
      the same areas of the human lung. However, alterations in structure at this level
      of the lung are not well reflected by measuring FEV1 until substantial structural
      changes have occurred. Measures of the lung function that reflect the functional
      mechanics of airways smaller than 2 mm in diameter are considered to be more
      relevant. At least one epidemiologic study has provided evidence that small
      airway functions may be relevant to effects of prolonged exposure to environments
      with high concentrations of oxidants. A considerable body of physiologic data has
      established that flow rates measured during the terminal portion of a maximum
      expiratory flow-volume (MEFV) curve are largely governed by airways smaller than
      2 mm in diameter A similar interpretation has been given to changes in the slope
      of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve.
      Despite the attractiveness of these measures in relation to airway physiology,
      some data suggest that measurements of flow via the terminal portions of MEFV and
      SBNW curves have much greater within-subject variability than forced vital
      capacity (FVC and FEV1. The present study was undertaken as part of a larger
      feasibility study to develop methods to study the effects of prolonged exposure
      to elevated ambient ozone levels on lung function in adolescents. A convenience
      sample of 239 freshmen (ages 16-20 years) entering the University of California,
      Berkeley were recruited to participate in this protocol. All were lifelong
      residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were
      studied on two occasions five to seven days apart. At each test session, subjects
      performed up to eight forced expiratory maneuvers to produce three acceptable and
      reproducible MEFV curves by modified American Thoracic Society criteria. Tests of
      SBNW were then performed on the basis of detailed criteria for validity and
      reproducibility. Eight attempts to generate three curves were allowed. The delta
      N2 was obtained by a least-squares regression of nitrogen concentrations between
      the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume
      (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and
      delta N2 were the principal outcomes. Variance components were estimated with a
      nested random effects model with adjustments for important covariates. The
      average within-subject coefficients of variation (+/-SD of distribution of means)
      for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8
      (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4
      (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/
      17.0). The variance attributed to test session was less than 1% for all measures.
      The percentages of variance due to within-subject variation for each measure
      (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1
      3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested,
      234 (97.9%) could provide at least two acceptable MEFV curves, but only 218
      (91.2%) could provide at least two acceptable SBNW curves. The results were
      unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)

PMID- 9563089
TI  - [Genetic expression of nerve growth factor in the central nervous system.
      Evaluation of an experimental model for Alzheimer's dementia].
AB  - INTRODUCTION AND OBJECTIVE: Several authors have suggested that loss of neuronal
      trophic support may be an important element in the physiopathology of
      degenerative conditions of the central nervous system such as Alzheimer's
      dementia, Parkinson's disease or amyotrophic lateral sclerosis amongst others. In
      the light of present knowledge, the survival of cholinergic populations of the
      anterior basal cerebrum, closely involved with cognitive processes of memory and
      learning, is associated with adequate function of the neural growth factor (NGF).
      These populations are markedly damaged in Alzheimer's disease, and this has been
      correlated with the progressive loss of memory and intellectual involvement seen
      in this disorder. The model used in this study was based on section of the
      septohippocampal connecting pathways, so that transport of regulatory impulses
      from the hippocampus to the medial septum was interrupted. This has lethal
      results for the cholinergic neurons of the latter. We have developed a study
      designed to characterize the expression of the gene of NGF in different regions
      of the brain, involved in cholinergic neurotransmission in healthy and in damaged
      tissue. MATERIAL AND METHODS: We used a molecular hybridization technique with a
      cDNA catheter complementary to the radio-isotope marked NGF human gene. RESULTS
      AND CONCLUSIONS: The highest levels of expression were found in the healthy
      cortex and hippocampus. The reduction in the levels of mRNA of NGF in the damaged
      hippocampus supports the current thesis which considers synaptic activity to be a
      major regulator of the synthesis of this molecule in the brain.

PMID- 9563090
TI  - [Abnormal movements in a case of extrapontine myelinolysis. Review of the
      literature].
AB  - INTRODUCTION AND CLINICAL CASE: We present a case of extra-pontine myelinolysis
      caused by acute hypernatraemia in which a complex picture of late onset
      extrapyramdial features, choreodystonia and parkinsonism developed. Repeated
      physical examinations, neurophysiological and neuroimaging studies using magnetic
      resonance all indicated an extra-pontine site of the lesions, which symmetrically
      affected the striate and to a lesser extent both thalami. We review the relevant
      literature available and analyze the cases described as having abnormal movements
      associated with a myelinolytic syndrome. CONCLUSIONS: Extra-pontine myelinolysis
      is a cause of acquired dystonia, chorea and parkinsonism, generally of late onset
      and with varying response to treatment. The association of hypernatraemia,
      hyperglycaemia and liver transplant seem to predispose to the development of
      extra-pontine lesions.

PMID- 9563091
TI  - [Parkinsonian hemi-syndrome as the initial manifestation of supratentorial cystic
      hemangioblastoma in a patient with Von Hippel-Lindau disease].
AB  - INTRODUCTION: Retino-cerebellar hemangioblastomatosis or Von Hippel-Lindau (VHL)
      disease is a phacomatosis with a dominant autosomal pattern of inheritance, which
      is characterized by the presence of hemangioblastomas of the central nervous
      system (cerebellum and spinal medulla), retinal angiomas and tumors
      (pheochromocytoma, clear cell carcinoma) or cysts of the abdominal viscera.
      CLINICAL CASE: We present the case of a 22 year old female with Von Hippel-Lindau
      disease, in whom a cystic hemangioblastoma of the basal ganglia of the left
      hemisphere was diagnosed when she complained of difficulty in carrying out fine
      movements of the right hand and tremor for some months. The supratenorial site of
      cystic hemangioblastomas in the clinical context of Von Hippel-Lindau disease is
      very rare and clinical presentation of a parkinsonian hemisyndrome is
      exceptional. In our search through the literature we have found tumors with many
      types of histology (meningiomas, glial tumors, craniopharyngioma, epidermoid
      cysts) in the origin of tumoral parkinsonism. CONCLUSIONS: However, we have found
      no previous case of cystic hemangioblastomas. We also emphasize that there was
      full resolution of the condition after total removal of the tumour.

PMID- 9563094
TI  - [Is it possible to diagnose all adult-onset seizures and epilepsies?].
AB  - Our capacity to recognize clinical situations--such as epileptic crises--depends
      on observation, clinical analysis, evolution, response to drugs and the
      establishment of a rational differential diagnosis of crises. Sometimes, with all
      these clinical factors and complementary tests, epileptic crises may be
      recognized and diagnosed. Thanks to current advances in neuroimaging and other
      complementary tests, we can recognize all the various ways in which
      cerebrovascular disease becomes manifest in relation to crises and epilepsies
      together with normal aging and dementias, and genetic factors which affect the
      occurrence of crises in senile patients and modulate aging of the brain.
      Considering the above data, it is possible to diagnose as symptomatic 80-90% of
      cases of epilepsy occurring in senile patients. There will be fewer cryptogenic
      and idiopathic cases of epilepsy in adults. The most outstanding epidemiological
      studies give high percentages of idiopathic cases in adults and the elderly. On
      critical analysis, no detailed examination is described for each patient to
      determine the aetiology, before labelling the case as idiopathic. In young
      adults, many so-called idiopathic cases of genetic origin, and occur during
      adolescence. These same types of epilepsy may been seen in young adults and in
      adolescents. Other genetic syndromes include familial temporal epilepsy,
      nocturnal familial frontal epilepsy, etc.

PMID- 9563092
TI  - [Biopathology of craniocerebral injuries: experimental models].
AB  - INTRODUCTION: In traumatic brain injury the secondary damage is responsible for
      the majority of the clinical and pathological sequels. This circumstance together
      with the difficulties of acquiring well preserved brain material for specialized
      neuropathological study impair the understanding of processes implied in their
      pathophysiology. DEVELOPMENT AND CONCLUSIONS: The development of experimental
      models has played an outstanding role for the better knowledge of these
      processes. For the development of standardized experimental models the
      biophysical and anatomical characteristics of brain and skull of the various
      utilized species have to be considered, but the physiological, neurochemical and
      molecular peculiarities must also be taken into account. Various in vivo models
      have been developed, inducing direct impact to the skull or to the brain, or
      mimicking lesions subsequent to craniocerebral trauma, such as subarachnoid
      hemorrhage, hematoma or necrosis. To analyze the molecular mechanisms of cellular
      response in vitro models have been developed. A great amount of cells in the
      contusional area die immediately following traumatic brain injury, but a still
      higher number of cells will undergo in the following hours. This second wave of
      neuronal death is induced by phenomena such as secondary axotomy and brain edema.
      In the pathogenesis of both the damage of cytoplasmic membrane is involved.

PMID- 9563095
TI  - [Epilepsy and migraine].
AB  - Migraine and epilepsy are two clearly different syndromes. All they have in
      common is that both cause paroxystic neurological phenomena. However, the
      frequency of epilepsy in patients with migraine, and migraine in those with
      epilepsy seems to be higher than one would expect. This suggests there may be
      comorbidity in both conditions. Analysis of this comorbidity is very important
      since it may give clues as to the physio-pathology and aetiology of certain
      disorders. This paper analyses the existence of migraine-epilepsy comorbidity and
      the levels at which it occurs. This coexistence may be due to the episode of one,
      for example the aura of a migrainous attack, triggering off the other condition,
      that is an epileptic crisis. So, it may be that the 'migrainous illness' causes
      the 'epileptic illness' or the other way around. Their coexistence may be due to
      a risk factor which is common to both, since it has caused a cerebral lesion
      which is the cause of both disorders. Finally, a risk factor may have a direct
      effect, without requiring the intervention of an intermediate cerebral lesion to
      cause both migraine and epilepsy. This last possibility is particularly
      attractive to explain the comorbidity of migraine with an aura and genetically
      determined epilepsy.

PMID- 9563093
TI  - [Composition and structure of the neuronal membrane: molecular basis of its
      physiology and pathology].
AB  - INTRODUCTION AND OBJECTIVE: Neurons besides its ability to selectively detect
      signals from their surrounding, are able to integrate then in time and space when
      transmitting their message to other cells. This exceptional ability of the neuron
      is mainly due to the composition and characteristics of its plasma membrane. In
      this review, starting with a description of the general principles of cell
      membrane organization, on which the nerve cell membrane structure is based, we
      describe the structures and functions which are unique and peculiar to the
      neuronal membrane and its implications in pathological processes. DEVELOPMENT:
      This review article starts with a description of the lipids forming the neuronal
      membrane, and the forces which maintain their cohesion to form the basic
      structure of the membrane. We describe some of the intrinsic biophysical
      properties of biological bilayers, and also to make special mention of the
      neuronal membrane proteins, both peripheral and integral proteins which are,
      finally, responsible for specificity and functional differentiation of the
      neurons. CONCLUSIONS: Now a days, it is becoming clear that the knowledge of the
      neuronal membrane at the molecular level, specially the proteins involved in
      neuronal activity, is basic to understand neuronal physiology and pathology. Many
      disorders of the nervous system have their origins in defective synthesis or
      incorrect functioning of a particular protein in the neuronal membrane.

PMID- 9563096
TI  - [Diagnosis of seizures originating in the amygdala and the hippocampus].
AB  - INTRODUCTION: Lesions in the hippocampus of some epileptic patients were first
      described one hundred and seventy years ago. Since then our knowledge of the
      relationship between epileptic seizures and temporal lobe lesions has greatly
      improved. DEVELOPMENT: The aim of this paper is to systematize the symptomatology
      of the hippocampus and amygdala seizures. These seizures may have a great number
      of different clinical features: special 'loss' or 'impairment of consciousness',
      epileptic automatisms and autonomic changes. Moreover, at the beginning of
      seizures some patients have reported experiences having subjective qualities
      similar to those experienced in everyday life. P Gloor named them 'experiential
      phenomena' and subdivided them into affective (eg: fear), perceptual (eg: visual
      hallucinations) and mnemonic (eg: 'deja vu' illusion). CONCLUSION: It is very
      important to know the contribution of the hippocampus and the amygdala to the
      symptomatology of temporal lobe seizures due to the progress of MRI diagnostic
      possibilities that are improving the surgical outcome.

PMID- 9563097
TI  - [Epilepsy, society and rights].
AB  - Although from the medical point of view epilepsy is considered to be a
      neurological disorder, this has not always been so. It was once included in the
      group of psychiatric disorders by the medical profession and others. In the case
      law of the Supreme Court, epilepsy is defined as a typical endogenous psychosis,
      and therefore as insanity. This would lead to its inclusion in the grounds for
      exoneration from criminal responsibility and has therefore been invoked as
      grounds for immunity from prosecution by many offenders. This has proved to be a
      two-edged sword, since the concept of insanity has led to these patients
      suffering social rejection. Medicine and Law have never found it easy to
      understand each other. However, now more than ever, some degree of mutual
      understanding is necessary when passing judgement on a person, since the Law
      progresses more slowly than Medicine does. Thus, today we would question a series
      of offences referred to in this paper, which used to be classified as insanity
      due to epilepsy. From a legal point of view we advocate a clear classification of
      epilepsy as a neurological disorder. This would doubtless lead to epileptics
      being more socially acceptable.

PMID- 9563099
TI  - [Diagnostic focus on the child with myoclonic seizures in isolation or associated
      with other types of seizures].
AB  - Myoclonus may be observed in children with mild or severe epileptic syndromes.
      Both types are seen at characteristic ages, together with other factors:
      aetiology, family history, hereditary pattern, effect on psychomotor development
      and EEG-EMG findings. In children with progressive or degenerative
      encephalopathies and myoclonus, better known as progressive myoclonic epilepsy,
      there are also specific clinical data, together with biological and genetic
      markers which permit identification. The most specific clinical characteristics
      of each of these clinical pictures are described, as are the complementary tests
      which permit confirmation of these diagnoses.

PMID- 9563098
TI  - [Diagnostic problems in childhood epilepsy].
AB  - The correct diagnosis of the epileptic patient must establish the type of
      seizures according to the 1981 ILAE ICES, and the epileptic syndrome according to
      the 1989 ILAE ICE. Some children, at the onset of epilepsy, are difficult to
      classify. These are the reasons which can cause the diagnostic problems: 1.
      Misdiagnosis as epilepsy the non-epileptic seizures. 2. Misclassifying the type
      of seizures for incomplete or inadequate information. 3. Misclassifying the type
      of epileptic syndromes due to overlapping of different syndromes or because the
      patient presents more than one syndrome at the same time or during the course of
      the illness. It follows from this that it is not easy to classify all cases of
      epilepsy. The 'forced' as inadequate classification can give rise to a
      therapeutic or prognostic misdiagnosis.

PMID- 9563100
TI  - [Diagnostic focus on the child with generalized seizures].
AB  - We have carried out an overall analysis of the diagnostic approach to generalized
      epileptic crises in children. It is emphasized that the clinical history is an
      essential factor in reaching the correct diagnosis. This is inevitably followed
      by a general and then a specifically neurological physical examination. Four
      parameters are considered in order to reach an initial diagnosis: a) The
      probability of the various types of crises in view of the timing of the clinical
      features. b) Knowledge of the clinical characteristics of the types of epileptic
      crises which may occur. c) The interrelation of these two parameters, seeking a
      specific syndrome which would fit the facts. d) Consideration of the most usual
      etiological factors of the tentative diagnosis. Subsequently the necessary
      complementary tests are carried out, but these are always based on rational
      clinical grounds. The commonest clinical and electroencephalic characteristics of
      generalized epileptic crises (except for myoclonic crises) are discussed. These
      are neonatal crises, 'absence', generalized tonic-clonic crisis, generalized
      crises with predisposing activation mechanisms, West's syndrome and the Lennox
      Gastaut syndrome. The diagnostic value of other complementary tests in such
      crises is considered.

PMID- 9563102
TI  - [Posterior fossa tumors in children].

PMID- 9563101
TI  - [Diagnostic focus on the child with epilepsy and neuropsychological
      deterioration].
AB  - Symptomatic epilepsy secondary to hereditary metabolic or degenerative disorders,
      is usually associated to neurological deterioration. Though epilepsy by itself
      does not induce neurological deterioration, we should remind that some epileptics
      encephalopathies, such as the West or Lennox-Gastaut syndromes, do actually
      induce limited neurological deterioration. Furthermore, in some forms of complex
      partial epilepsy, motor problems and behavior disorders can be observed,
      specially in adolescents with temporary lobe epilepsy. Other forms of epilepsy,
      such as the atypical benign partial epilepsy or the Landau-Kleffner syndrome, can
      present a certain degree of cognitive deterioration in the evolution, although
      they can recover later lost functions, totally or partially. The evolution of
      some refractory epilepsy, as patients are submitted to a multiple treatments, can
      make us suspect a degenerative disease. In some cases, the diagnosis of the
      hereditary metabolic and heredodegeneratives diseases can be made by the
      characteristics of the seizures but in most cases the diagnosis will be
      established by the symptoms of the basic disease and the lab data.

PMID- 9563103
TI  - ["Le scaphandre et le papillon"].

PMID- 9563104
TI  - Analysis of aging and degeneration of the human intervertebral disc. Comparison
      of surgical specimens with normal controls.
AB  - STUDY DESIGN: A prospective analysis of 33 control and 39 surgical human lumbar
      disc specimens from the anulus was undertaken to assess disc cell extracellular
      matrix production and cell function. The authors of this study analyzed
      immunohistochemical distributions of Types I, II, III and VI collagen, in situ
      localization of apoptotic disc cells, and tartrate-resistant acid phosphatase
      localization. OBJECTIVES: To quantify the incidence of apoptotic cell death in
      the anulus; examine the collagen distribution in the pericellular, territorial,
      and interterritorial matrix; examine matrix cell degeneration; and compare
      diseased tissue with normal tissue from control individuals. SUMMARY OF THE
      BACKGROUND DATA: Previous studies of disc histopathology have focused on
      extracellular matrix morphology and on biochemical synthetic and degenerative
      changes, but little is understood about the cell populations within the disc that
      are responsible for these changes. METHODS: In this study light microscopy,
      immunohistochemistry, enzyme histochemistry, and in situ hybridization were used
      to examine 33 patient and 39 control specimens of human anulus obtained either
      via surgical procedures or from donors to the Cooperative Human Tissue Network.
      RESULTS: The high incidence of apoptotic cell death was significantly greater in
      the control group (73.1 +/- 5.1% [mean +/- SEM]; n = 20) than among surgical
      specimens (53.5 +/- 5.6%; n = 20; P < 0.001); this was probably a result of the
      significantly greater average age in the control population (57.2 +/- 3.1 years)
      compared with that in the patient population (44.3 +/- 3.2 years; P < 0.001).
      Immunohistochemistry yielded findings that led to an expanded appreciation of the
      greatly modified extracellular domains that surrounded disc cells during aging
      and degeneration in both study groups. Enzyme histochemistry revealed the
      presence of tartrate-resistant acid phosphatase activity in human disc cells.
      CONCLUSIONS: These findings reveal that there is a high incidence of apoptosis in
      the intervertebral disc. Surviving cells are not synthetically inactive but are,
      rather, producing inappropriate matrix products during aging and degeneration. In
      certain instances it appears that the matrix surrounding the cell may form an
      isolation barrier, which may influence individual cell activity and intercellular
      communication. These results point to the need to 1) more fully understand the
      cause of disc cell death via apoptosis and to determine whether this programmed
      cell death can be reversed or halted, and 2) more fully understand the dynamic
      relation between disc cells and the surrounding extracellular matrix, which they
      produce and remodel. The factors regulating extracellular matrix-disc cell
      homeostasis in the disc are unknown, as is the relation between extracellular
      matrix and disc cell functional modulation. The morphologic findings of this
      study suggest that these issues are important considerations in disc cell
      biology. The identification of tartrate-resistant acid phosphatase activity in
      disc cells allows for a new area of study of disc extracellular matrix
      remodelling. In summary, these new perspectives provide new parameters with which
      to assess disc cell health and function.

PMID- 9563105
TI  - Cervical interbody fusion cages. An animal model with and without bone
      morphogenetic protein.
AB  - STUDY DESIGN: The Alpine goat model for multilevel anterior cervical discectomy
      and fusion was used to analyze the use of an intervertebral fusion device to
      promote an arthrodesis after anterior cervical discectomy. Comparisons were drawn
      with biomechanical, histologic, and radiographic data. OBJECTIVES: To analyze the
      use of an intervertebral fusion device, with and without a bone graft substitute,
      to promote an arthrodesis anterior cervical discectomy. SUMMARY OF BACKGROUND
      DATA: In previous studies, the goat cervical spine has proven to be an excellent
      model for examining the healing of fusions using bone grafts, instrumentation, or
      bone substitutes. METHODS: Three-level anterior cervical dissectomies were
      performed on 21 mature Alpine goats. Three treatment groups of seven goats each
      were used. Group I used a standard titanium cervical BAK device filled with
      autogenous bone graft. Group II used a hydroxyapatite-coated BAK device filled
      with autogenous bone graft. Group III used a BAK device filled with recombinant
      human bone morphogenetic protein-2. RESULTS: Radiographically, no cages became
      displaced. Lucencies were seen around 3 of the 21 cages in Group 1, 4 cages in
      Group II, and none in Group III. Fluorochrome analysis revealed that the
      recombinant human bone morphogenetic protein-2-filled cages had an accelerated
      rate of bone growth around and through each cage-vertebral body interface at 3
      weeks. A successful arthrodesis was also more likely with a recombinant human
      bone morphogenetic protein-2-filled cage (95%) than the hydroxyapatite-coated
      (62%) or the standard (48%) cage. Biomechanical stiffness testing did not reveal
      any statistically significant differences between the three groups. There was a
      tendency for successfully arthrodesed interspaces to be stiffer than those that
      were not. CONCLUSIONS: The use of a threaded intervertebral fusion cage, with or
      without hydroxyapatite coating, filled with autogenous bone graft provides a
      fusion rate that is slightly better than those previously reported using
      autogenous interbody bone grafts with or without plate stabilization. Recombinant
      human bone morphogenetic protein-2-filled cages resulted in a much higher
      arthrodesis rate and accelerated bone formation compared with either autogenous
      bone-filled BAK devices, or autogenous interbody bone grafts with or without
      plate stabilization.

PMID- 9563106
TI  - The effects of rigid spinal instrumentation and solid bony fusion on spinal
      kinematics. A posterolateral spinal arthrodesis model.
AB  - STUDY DESIGN: Spinal kinematics after the implementation of rigid spinal
      instrumentation or the achievement of a solid fusion was studied using a sheep
      posterolateral spinal arthrodesis model. OBJECTIVE: To investigate the effects of
      rigid spinal instrumentation or solid fusion on spinal kinematic parameters.
      SUMMARY OF BACKGROUND DATA: Numerous studies have attempted to define spinal
      instability in terms of kinematics. Recent in vitro studies have documented the
      neutral zone, or a measure of spinal laxity, as more sensitive to spinal
      instability than the range of motion. METHODS: Seven skeletally mature sheep
      underwent a single-level posterolateral lumbar arthrodesis using autologous bone
      graft augmented with transpedicular screw fixation. The animals were killed 4
      months after surgery. The identical surgical procedures were performed in seven
      sheep cadaveric spines, which served as acute postoperative controls. Each
      functional spinal unit was tested biomechanically before and after hardware
      removal. The experimental control groups consisted of destabilized spines and
      spines that underwent transpedicular screw fixation alone, whereas the fusion
      groups included spines that underwent posterolateral fusion alone or
      posterolateral fusion with instrumentation. RESULTS: Rigid instrumentation and
      solid fusion significantly decreased the neutral zone and range of motion in all
      testing modes. In axial rotation and lateral bending, solid fusion reduced the
      range of motion significantly more than transpedicular screw fixation alone.
      However, in all testing modes, the neutral zones showed no statistical difference
      between transpedicular screw fixation alone and fusion groups. CONCLUSIONS: The
      range of motion was an equivalent or better indicator of fixation or fusion
      stability compared with the neutral zone. Moreover, the immediate postoperative
      fixation stability, even if using transpedicular screw fixation, was less than
      the stability present after a solid fusion.

PMID- 9563107
TI  - Trunk muscle co-contraction increases during fatiguing, isometric, lateral bend
      exertions. Possible implications for spine stability.
AB  - STUDY DESIGN: Surface electromyographic activities were recorded from bilateral
      trunk muscles as test participants maintained a 50% maximum, voluntary,
      isometric, lateral bend contraction to volitional exhaustion. OBJECTIVES: To
      challenge the trunk with a prolonged lateral bend task and observe the responses
      of the agonist and antagonist muscles to the resulting fatigue. SUMMARY OF
      BACKGROUND DATA: Lateral bend exertions of the trunk have been identified as a
      risk factor for injury to spine tissues. However, little is known about the
      response of spine muscles to fatigue and the subsequent implications for spine
      stability, joint loading, and tissue injury. Surface electromyography provides a
      window on muscle loading and progressive fatigue. METHODS: Eleven male
      participants performed a set of maximum lateral bend exertions at the start of
      the trial, then maintained an upright standing posture while resisting 50% of the
      maximum moment until volitional exhaustion, then performed another set of maximum
      contractions. All contractions were isometric. Measurements were made, throughout
      each contraction, of the lateral bend moment and abdominal and trunk extensor
      electromyographic activities at six bilateral surface electromyography sites.
      Electromyographic amplitude and mean power frequency were calculated with 500
      millisecond segments recorded serially every 800 milliseconds. Mean values were
      calculated with data from the first and last 5% of the trial durations.
      Statistics determined if fatigue had a significant effect on maximum moment and
      the electromyographic statistics for each muscle site. RESULTS: Fatigue resulted
      in a significant decrease in maximum lateral bend moment and increase in moment
      variability. Decreases in mean power frequency, indicating fatigue, were observed
      in three agonists (the trunk extensors) and one antagonist muscle. Unfatigued
      agonist electromyographic amplitudes correlated well with the mechanical
      advantage of muscles to generate lateral bend moments. Unfatigued antagonist
      activities were low except for the thoracic erector spinae. The agonists and
      antagonists demonstrated average increases of 17% and 8%, respectively, when
      pooled across muscles. Much of this change was predicted to have been associated
      with increases in co-contracting muscle forces. CONCLUSIONS: The trunk responded
      to a prolonged, lateral bend contraction by increasing co-contraction as agonist
      trunk muscles fatigued. It was proposed that the fatigue compromised neural
      coordination and that the co-contraction served to maintain spine stability.

PMID- 9563108
TI  - Multicycle mechanical performance of titanium and stainless steel transpedicular
      spine implants.
AB  - STUDY DESIGN: This was a prospective in vitro study comparing titanium alloy and
      stainless steel alloy in transpedicular spine implants from two different
      manufactures. OBJECTIVE: To compare the multicycle mechanical performance of
      these two alloys, used in each of two different implant designs. SUMMARY OF
      BACKGROUND DATA: Transpedicular spine implants primarily have been manufactured
      from stainless steel, but titanium alloy offers imaging advantages. However, the
      notch sensitivity of titanium alloy has caused concern regarding how implants
      made from this material will compare in stiffness and fatigue life with implants
      made from stainless steel. METHODS: Twenty-four implants (two alloys, two
      designs, six implants per group) were mounted in machined polyethylene wafers and
      repetitively loaded (up to 1 million cycles) from 80 N to 800 N using a 5-Hertz
      sinusoidal waveform. Load and displacement data were automatically and
      periodically sampled throughout the entire test. RESULTS: Implant stiffness
      increased with cycle load number, reached a steady state, then declined just
      before fatigue failure. Stiffness varied less in titanium transpedicular spine
      implants than in their stainless counterparts. All stainless steel implant types
      were stiffer (steady-state value, P < 0.0001) than their titanium alloy
      counterparts. One titanium implant design failed with fewer (P < 0.05) load
      cycles than its stainless steel counterpart, whereas a stainless steel implant of
      another design failed with fewer (P < 0.002) load cycles than its titanium
      counterpart. Overall, fatigue life, i.e., the total number of load cycles until
      failure, was related to implant type (P < 0.0001), but not to implant material.
      CONCLUSIONS: A transpedicular spine implant's fatigue lifetime depends on both
      the design and the material and cannot be judged on material alone. Stainless
      steel implants are stiffer than titanium alloy implants of equal design and size;
      however, for those designs in which the fatigue life of the titanium alloy
      version is superior, enlargement of the implant's components can compensate for
      titanium's lower modulus of elasticity and result in an implant equally stiff as
      its stainless steel counterpart. Such an implant made from titanium alloy would
      then be clinically preferable because of titanium's previously reported imaging
      advantages.

PMID- 9563109
TI  - Long-term evaluation of vertebral artery injuries following cervical spine trauma
      using magnetic resonance angiography.
AB  - STUDY DESIGN: A prospective study to determine the long-term outcome of
      traumatically induced vertebral artery injuries. Magnetic resonance angiography
      was performed at the time of cervical injury and at a follow-up office visit.
      OBJECTIVE: To determine the long-term outcome in terms of arterial flow
      competency of traumatically induced vertebral artery injuries. SUMMARY OF
      BACKGROUND DATA: Vertebral artery injury associated with cervical spine trauma
      has been well documented; however its healing or nonhealing potential has not
      been elucidated. METHODS: During the 7-month period from July 1993 to January
      1994, all patients admitted to the authors' institution with cervical spine
      injuries underwent magnetic resonance imaging and magnetic resonance angiography
      of the cervical spine to determine the patency of their vertebral arteries.
      Magnetic resonance angiography was performed at the time of injury and at a
      follow-up office visit. Twelve of 61 patients were found to have a lack of signal
      flow within one of their vertebral vessels during this study period. RESULTS:
      Eighty-three percent of the patients (five of six) who were available for follow
      up observation in this study did not manifest flow reconstitution of their
      vertebral arteries after an average 25.8-month follow-up period. CONCLUSIONS:
      According to these data, most patients with vertebral artery injuries after
      nonpenetrating cervical spine trauma do not reconstitute flow in the injured
      vertebral arteries. This lack of flow must be considered if future surgery in
      this region of the cervical spine is contemplated.

PMID- 9563110
TI  - A study of the diagnostic accuracy and reliability of the Scoliometer and Adam's
      forward bend test.
AB  - STUDY DESIGN: Study of the diagnostic accuracy and interexaminer reliability of
      scoliosis diagnostic tests. OBJECTIVES: To estimate the sensitivity, specificity,
      and predictive value of the Scoliometer (National Scoliosis Foundation,
      Watertown, MA) and Adam's forward bend test in diagnosing scoliosis, and to
      determine the interexaminer reliability of the Scoliometer and Adam's forward
      bend test. SUMMARY OF BACKGROUND DATA: Exposure to diagnostic radiation in
      patients with adolescent idiopathic scoliosis may result in a small but
      significant increase in cancer rates. The full-spine radiographic examination
      remains the standard procedure for the assessment of scoliosis. There is a need
      for a valid and reliable noinvasive test to assess scoliosis. METHODS: Two
      examiners independently assessed 105 patients presenting to a scoliosis clinic
      for trunk asymmetry with Adam's forward bend test and axial trunk rotation with
      the Scoliometer. The Cobb method served as the gold standard. RESULTS: The
      interexaminer agreement for the Scoliometer is excellent in the thoracic spine
      and substantial in the lumbar spine. The interexaminer measurement error shows
      poor precision for thoracic and lumbar Scoliometer measurements. The
      interexaminer agreement for Adam's forward bend test is substantial in the
      thoracic spine and poor in the lumbar spine. Adam's forward bend test is more
      sensitive than the Scoliometer in detecting thoracic curves measuring 20 degrees
      or more by the Cobb method. Receiver operating characteristic curve analysis
      suggests that the use of the Scoliometer marginally improves the ability of
      diagnosing a scoliosis in the thoracic spine. CONCLUSIONS: The Scoliometer and
      Adam's forward bend tests have adequate interexaminer reliability for the
      assessment of thoracic curves. The Scoliometer has better interexaminer agreement
      in the lumbar spine. However, the Scoliometer has a high level of interexaminer
      measurement error that limits its use as an outcome instrument. Because Adam's
      forward bend test is more sensitive than the Scoliometer, the authors believe
      that it remains the best noninvasive clinical test to evaluate scoliosis.

PMID- 9563111
TI  - Traction versus supine side bending. Which technique best determines curve
      flexibility?
AB  - STUDY DESIGN: A prospective study performed in two institutions where patients
      scheduled for surgical management of scoliosis were evaluated with traction and
      supine side bending radiographs to determine curve flexibility. OBJECTIVE: To
      determine if there is a difference in the flexibility of curves as determined by
      side bending or traction films. METHODS: Fifty-eight patients scheduled for
      surgery underwent preoperative radiographic evaluation using supine side bending
      and traction radiographs. The surgeons were free to use the information as they
      saw fit in determining levels of fusion. All curves were measured using the
      method of Cobb. Curves were analyzed in three groups: > 60 degrees, 50-60
      degrees, and < 50 degrees. A comparison then was made between the traction and
      side bend films to determine which method demonstrated greater flexibility.
      Measurement error was assumed to be +/- 5 degrees. If the measurements were
      within 5 degrees, then the two methods were considered to be equivalent. RESULTS:
      In curves > 60 degrees, greater flexibility was seen on traction films. In curves
      < 50 degrees, side bending showed greater flexibility. In curves between 50
      degrees and 60 degrees, side bending showed greater flexibility in the thoracic
      spine, whereas in the lumbar spine both films showed equivalent flexibility.
      CONCLUSIONS: Traction shows greater curve flexibility in curves > 50 degrees,
      whereas in curves < 50 degrees, side bending shows greater flexibility.

PMID- 9563112
TI  - Is hormone replacement therapy a risk factor for low back pain among
      postmenopausal women?
AB  - STUDY DESIGN: Cross-sectional study with two age cohorts. OBJECTIVE: To assess
      whether women receiving hormone replacement therapy after menopause have a higher
      prevalence of back problems than women who do not receive such treatment.
      BACKGROUND: Back pain is a common medical problem throughout life and especially
      during pregnancy. Hormonal factors have been proposed as a possible contributor.
      PATIENTS AND METHODS: A validated postal questionnaire was sent in early 1995 to
      all 1324 women of 55 years and 56 years of age residing in Linkoping, Sweden.
      This questionnaire included questions about current hormone replacement
      treatment, previous and current back problems, medical care for back problems,
      parity, exercise and smoking habits, and occupation. RESULTS: The questionnaire
      was returned by 84.7% of the women. There was a significant, albeit weak,
      positive association between current use of hormone replacement treatment and low
      back pain. Previous back problems during pregnancy was a strong risk factor for
      current back pain, whereas neither current smoking nor regular physical exercise
      was a risk factor according to multiple logistic regression analysis. The
      interaction of smoking and an occupation involving heavy lifting significantly
      affected back pain. CONCLUSIONS: Women receiving hormone replacement treatment
      had a slightly, but significantly, higher prevalence of current back pain than
      nonusers (48% vs. 42%, respectively, P < 0.05), which could not be explained by
      differences in occupation, smoking habits, or current physical activity. Although
      the association between hormone replacement therapy and back problems is weak and
      probably of minor clinical importance, it is speculated that hormonal effects on
      joints and ligaments may be involved.

PMID- 9563113
TI  - 5-year reoperation rates after different types of lumbar spine surgery.
AB  - STUDY DESIGN: Population-based cohort study of Washington State patients who
      underwent lumbar spine surgery for degenerative conditions in 1988. OBJECTIVES:
      To compare complications and reoperation rates during the 5-year period after
      surgery between patients who have undergone lumbar spine fusion surgery and those
      who have undergone laminectomy or discectomy alone. SUMMARY OF BACKGROUND DATA:
      Spinal fusion is associated with wider surgical exposure, more extensive
      dissection, and longer operative times than lumbar surgery without fusion, and
      previous studies have shown higher complication rates and hospital charges
      associated with these more complex procedures. In elderly patients, spinal fusion
      operations were associated with higher mortality rates than laminectomy or
      discectomy alone, and reoperation rates were not lower. In the current study,
      reoperations, mortality, and complications following lumbar spine surgery were
      examined for the general population. METHODS: A statewide hospital discharge
      database was used to identify all Washington patients who underwent spine surgery
      in 1988 and to determine the rate of reoperation during the subsequent 5 years.
      Administrative records also were used to identify complications, mortality, and
      hospital charges associated with the operations. Unadjusted complication and
      reoperation rates for the groups were compared using chi-square statistics.
      Adjusted rates were compared using logistic regression and proportional hazards
      (Cox) regression after controlling for age, gender, prior spine surgery,
      diagnosis, comorbidity, type of surgery, and coverage by Workers' Compensation.
      RESULTS: Of 6376 patients who underwent lumbar surgery for degenerative
      conditions in Washington in 1988, 1041 (16%) had operations involving spine
      fusion. Diagnoses of degenerative disc disease or possible instability were more
      frequent among patients undergoing fusion surgery, whereas herniated discs were
      more frequent among those undergoing discectomy or laminectomy alone.
      Complications were recorded in 18% of fusion patients and 7% of nonfusion
      patients (P < 0.01), but mortality rates did not differ. Unadjusted reoperation
      rates over the 5-year period were greater for patients who underwent fusion than
      for patients who underwent nonfusion surgery (18% vs. 15%, respectively), but
      after adjustment for baseline characteristics, fusion patients had only a
      slightly greater (and nonsignificant) risk of reoperation (relative risk 1.1,
      confidence interval .9-1.3). CONCLUSION: As in previous studies, complications in
      the current study occurred more frequently among patients who underwent lumbar
      spine fusion than among those who underwent laminectomy or discectomy alone.
      Reoperations were at least as frequent after fusion, but the authors could not
      assess treatment efficacy in terms of pain relief or improved function. Although
      the characteristics of patients undergoing fusion differed from those undergoing
      a laminectomy or discectomy alone, there appeared to be sufficient overlap in the
      clinical populations to warrant closer scrutiny of the safety, efficacy, and
      indications for spinal fusions, preferably in randomized trials.

PMID- 9563115
TI  - Low back pain in college athletes. A prospective study correlating lower
      extremity overuse or acquired ligamentous laxity with low back pain.
AB  - STUDY DESIGN: A prospective evaluation of the incidence of low back pain in
      college athletes was undertaken. OBJECTIVES: To evaluate prospectively leg length
      discrepancy, hip flexor tightness, and lower extremity acquired laxity or overuse
      as predictive factors for low back pain in college athletes. SUMMARY OF
      BACKGROUND DATA: A pilot study found an association between low back pain and the
      factors to be studied. Several allusions to the kinetic chain theory appear in
      the literature, but little prospective research has been done in examining the
      effects of lower extremity involvement on the back. METHODS: Two-hundred fifty
      seven college athletes representing nine varsity sports were screened during a
      preseason sports physical examination. Measures of flexibility, ligamentous
      stability, leg length discrepancy, and overuse syndromes were recorded. Athletes
      were observed throughout the ensuing year for low back pain requiring treatment
      by the athletic trainer. Those athletes with low back pain as the result of
      direct trauma to the region were excluded from the data. RESULTS: Twenty-four
      athletes (9.3%) received treatment for low back pain. Thirteen of 87 women (15%)
      compared with 11 of 170 men (6%) required treatment for low back pain (P =
      0.048). Of 57 athletes with lower extremity acquired laxity or overuse, low back
      pain developed in 14 (P < 0.001). CONCLUSIONS: Athletes with lower extremity
      acquired ligamentous laxity or overuse may be at risk for the development of
      noncontact low back pain during athletic competition. Female athletes with lower
      extremity involvement appeared to have a higher incidence of low back pain
      treatment compared with their male counterparts. Inflexibility of the lower
      extremities or leg length discrepancy were not associated with future low back
      pain treatment.

PMID- 9563114
TI  - Back pain in a large Canadian police force.
AB  - STUDY DESIGN: A survey of a random sample of 1002 members of the Royal Canadian
      Mounted Police to determine their experience with low back pain. OBJECTIVES: To
      determine the prevalence of low back pain among Royal Canadian Mounted Police
      members and to assess the validity of the perception that the patrol car seat and
      the duty belt are causing a higher rate of low back pain among members of the
      Royal Canadian Mounted Police than in the general population. SUMMARY OF
      BACKGROUND DATA: Low back pain is a common problem throughout the industrialized
      world, with reported 1-year prevalence rates between 25% and 62%. Prevalence of
      low back pain among people who drive motor vehicles for a significant part of the
      day appears higher than in the general population. Among police officers, 1-year
      prevalence rates of between 44% and 62% have been reported. METHODS: A
      computerized database of 14,897 serving regular members was used to identify a
      sample of officers on active duty. A low back pain questionnaire was mailed to
      each selected member, eliciting information regarding their experience with low
      back pain, their exposure to known and putative risk factors, and their opinions
      about the contribution of these potential risk factors. The respondents to the
      questionnaire remained anonymous. RESULTS: The response rate was 80%. The
      prevalence of "chronic or recurring low back pain since joining the force" was
      54.9%, which is comparable with the lifetime prevalence reported for the general
      population. Of those who reported having back problems, only 8.5% had such
      problems before joining the force. Seventy-six percent who had low back pain
      reported having a problem within the last year, giving an overall 1-year
      prevalence of 41.8%, which is comparable with that for the general population.
      The a priori assumption that driving or wearing a duty belt contributed to the
      problem was shared by most police officers surveyed. However, only about half of
      the members who replied drove for more than half the working day or wore the duty
      belt. These members had the same prevalence of low back pain as those who did not
      drive or wear the duty belt. CONCLUSIONS: The prevalence of low back pain in this
      police force is comparable with that in the general population, and driving a
      patrol car or wearing the duty belt does not appear to influence the prevalence
      rate in this population.

PMID- 9563116
TI  - The effect of postoperative nonsteroidal anti-inflammatory drug administration on
      spinal fusion.
AB  - STUDY DESIGN: The influence of ketorolac on spinal fusion was studied in a
      retrospective review of 288 patients who underwent an instrumented spinal fusion.
      OBJECTIVE: To assess the effect of postoperative ketorolac administration on
      subsequent fusion rates. SUMMARY OF BACKGROUND DATA: Nonsteroidal anti
      inflammatory drugs are widely used compounds, which are known to inhibit
      osteogenic activity and have been shown to decrease spinal fusion in an animal
      model. No previous studies have examined the influence of nonsteroidal anti
      inflammatory drugs on spinal fusion in clinical practice. METHODS: The medical
      records of 288 patients who underwent instrumented spinal fusion from L4 to the
      sacrum between 1991 and 1993 were reviewed retrospectively. The 121 patients who
      received no nonsteroidal anti-inflammatory drugs were compared with the 167
      patients who received ketorolac after surgery. The groups were demographically
      equivalent. RESULTS: Ketorolac had a significant adverse effect on fusion, with
      five nonunions in the nondrug group and 29 nonunions in the ketorolac group (P >
      0.001). Ketorolac administration also significantly decreased the fusion rate for
      subgroups including men, women, smokers, and nonsmokers. The odds ratio
      demonstrated that nonunion was approximately five times more likely after
      ketorolac administration. Cigarette smoking also decreased the fusion rate (P >
      0.01); smokers were 2.8 times more likely to develop nonunion. CONCLUSION: These
      data suggest that nonsteroidal anti-inflammatory drugs significantly inhibit
      spinal fusion at doses typically used for postoperative pain control. The authors
      recommend that these drugs be avoided in the early postoperative period.

PMID- 9563117
TI  - An unusual cause of low back pain. Osteomyelitis of the spinous process.
AB  - STUDY DESIGN: A case report of osteomyelitis of the spinous process. OBJECTIVE:
      To describe the diagnosis and successful treatment of a patient with spinous
      process osteomyelitis. SUMMARY OF BACKGROUND DATA: Spinous process osteomyelitis
      is exceedingly rare and may be misdiagnosed as paraspinal muscle strain,
      discitis, or vertebral body osteomyelitis. The clinical presentation of spinous
      process osteomyelitis is subtle, laboratory findings are nonspecific, and
      radiographs are often normal. METHODS: The diagnosis, treatment, and outcome of
      two patients with spinous process osteomyelitis (an adult and a child) with
      insidious, nonspecific lumbar pain and fever are reviewed. RESULTS: Magnetic
      resonance imaging with and without gadolinium enhancement demonstrated increased
      signal of the spinous process with paraspinous musculature enhancement, a finding
      consistent with spinous process osteomyelitis. Biopsy results demonstrated the
      presence of staphylococcus aureus in the child and no organisms in the adult.
      Treatment with intravenous antibiotics led to resolution in both cases.
      CONCLUSIONS: The use of magnetic resonance imaging technology permitted the early
      and accurate diagnosis of spinous process osteomyelitis.

PMID- 9563118
TI  - Assessment of lumbosacral fusion mass by angled radiography. Technical notes.
AB  - STUDY DESIGN: Lumbosacral fusion masses were assessed by angled radiography.
      OBJECTIVES: To introduce the use of the angled anteroposterior radiograph in the
      evaluation of the fusion mass at the lumbosacral region. SUMMARY OF BACKGROUND
      DATA: Determination of the presence and progress of the fusion mass at the
      lumbosacral junction may be difficult clinically and radiologically. Few studies
      regarding the use of the angled anteroposterior view of plain radiographs in
      evaluating L5-S1 fusion are available. METHODS: The patient was placed in the
      supine position, and an angled view of the lumbosacral junction was obtained.
      Radiography of the angled anteroposterior view was performed with the x-ray beam
      oriented toward the cranial portion at 50 degrees to 55 degrees relative to the x
      ray table. RESULTS: The use of the angled view of the lumbosacral junction
      eliminates the superimposition of the L5 transverse process on the posterior part
      of the superior ala of the sacrum, widens the L5-S1 intertransverse space, and
      enhances direct visualization. CONCLUSIONS: The use of the angled anteroposterior
      view on plain radiographs is recommended in the evaluation of the fusion status
      at L5-S1.

PMID- 9563119
TI  - [When to begin with androgen deprivation?].

PMID- 9563120
TI  - [What should be done in positive margins after radical prostatectomy?].
AB  - In the last years radical retropubic prostatectomy has become the treatment of
      choice for locally confined prostate cancer (PCa). However, in the literature
      local recurrence is described in 4-23% of patients with clinical stage T1-2
      prostate cancer and in 43% of patients with clinical stage T3 respectively. The
      problem is further aggravated that postoperatively raised PSA values are detected
      in 6-8% of patients with locally confined prostate cancer indicating either local
      residual tumor or systemic disease. Current datas show that wait-and-watch
      appears to be the best option for patients with locally confined prostate cancer
      and positive margins. In case of persistent or raising PSA-values following
      prostatectomy without detectable local recurrence or metastasis mere local
      therapy cannot be recommended. Primary radiotherapy should be considered in cases
      with confirmed clinical local recurrence without distant metastasis. Further
      prospective and randomized trials have to be initiated to identify the patients
      with positive margins who will benefit from adjuvant treatment.

PMID- 9563121
TI  - [What is the value of radical prostatectomy in lymph node positive prostate
      carcinoma?].
AB  - Improved diagnostic procedures prior to radical prostatectomy have led to a
      reduced rate of positive lymphnodes in patients with clinical stage T1-T2
      prostate cancer. According to current datas prolongation of survival following
      radical prostatectomy alone in patients with positive lymphnodes is not certain.
      Whether the recurrence free interval is prolonged is not known due to the lack of
      prospective randomized trials. Since it is not possible to define the small group
      of patients who will develop pronounced local symptoms after radical
      prostatectomy has been abandoned because of positive lymphnodes, radical
      prostatectomy cannot be recommended in general. In summary there is rarely an
      indication for radical prostatectomy in patients with stage T1-T2 prostate cancer
      and pelvic lymphnode metastasis.

PMID- 9563122
TI  - [Adjuvant therapy in lymph node positive prostate carcinoma?].
AB  - Few patients with prostate cancer metastatic to the lymphnodes can be cured by
      radiotherapy, radical prostatectomy or androgen deprivation. Inevitably serum PSA
      levels will rise after a few years whereas the clinical recurrence appears after
      5 to 10 years. Prospective trials regarding adjuvant treatment of lymphnode
      positive prostate cancer do not exist. Retrospective studies involving adjuvant
      endocrine treatment reveal a prolonged disease free survival time. Scientific
      proof of the best treatment for prostate cancer with lymphnode metastasis does
      not exist. The decision how to treat is based on our personal experience and
      philosophy as well as on our knowledge and interpretation of the available
      literature. The art of medicine is the feeling for the best treatment of each
      individual patient.

PMID- 9563124
TI  - [Complete androgen blockade versus monotherapy].
AB  - In a comparative analysis of 29 studies, maximal androgen deprivation (MAD) was
      not found to be superior to partial androgen deprivation. Thus, MAD cannot be
      regarded as the new gold standard. Most trials focus on quality of life which-
      given the palliative aim of the treatment--deserves special attention. This
      aspect has not yet been evaluated, however, in the largest multicenter study,
      intergroup study 0105. In patients with advanced bone metastasis or severe pain,
      MAD treatment should be begun because of the flare phenomenon. The synergistic
      effects of LHRH agonists on the prostate are currently being investigated. Since
      no clear prognostic factors exist and reduction of serum-PSA levels under MAD
      does not delay progression, the patient must help to make the decision of whether
      or not MAD should be begun.

PMID- 9563123
TI  - [Treatment of progressive, locally advanced prostate carcinoma].
AB  - Due to the lack of randomized and controlled trials comparing treatment options
      for locally advanced prostate cancer no clear cut therapeutical advise can be
      given. Currently, external beam radiotherapy is the form of treatment most often
      applied to which other therapeutic modalities have to be compared. Radical
      prostatectomy alone does not improve survival at this stage. The combination of
      local treatment modalities with neoadjuvant androgen deprivation seems to be a
      promising approach which has to be a promising approach which has to be evaluated
      in prospective clinical trials.

PMID- 9563125
TI  - [Intermittent versus continuous androgen blockade].
AB  - Androgenablation is the therapy of choice for the treatment of advanced and
      metastatic prostate cancer. However, in more than half of the patients the
      disease will ultimately progress within 2 years. Intermittent androgenablation
      through medical castration maintains the apoptotic potential. By periodically
      changing phases on and off treatment the quality of life of the patients is
      improved. Apart from reduced toxicity treatment costs are lowered and tumor
      progression is possibly delayed. In how far survival is influenced is presently
      not clear and remains to be evaluated in further clinical trials.

PMID- 9563126
TI  - [Anti-androgen withdrawal syndrome].
AB  - Since the mid-forties androgen deprivation is regarded the standard treatment of
      incurable prostate cancer. Antiandrogens can be given either as monotherapy or in
      combination with bilateral orchidectomy or gonadotropin-releasing-hormone
      analoga. Recently reports have been published that withdrawal of antiandrogens in
      patients with hormone-resistant prostate cancer caused reduction of PSA and
      clinical improvement. Thus, in patients who progress under maximal androgen
      blockade or antiandrogen-monotherapy the antiandrogen should first be withdrawn
      and-in case of monotherapy-be replaced by GnRH-analoga. In approximately 30-50%
      of the cases a reduction of serum-PSA can be expected lasting for approx. 6
      months. In some patients an improvement of symptoms and objective remission is
      observed.

PMID- 9563127
TI  - [Therapy of hormone refractory prostatic carcinoma].
AB  - In patients with hormone-resistant prostate cancer primary androgen deprivation
      eventually fails. The begin of secondary treatment is depending on clinical
      symptoms; since survival cannot be prolonged in progressive disease improvement
      of quality of life is of paramount importance. Altering of endocrine treatment
      and antiandrogen withdrawal can cause a transient improvement of the sense of
      well being. Single agent chemotherapy with little side effects should be
      preferred as compared with polychemotherapy since response rates do not exceed
      30%. Although 2/3 of the patients benefit from chemotherapy there is however no
      proof that it is superior to symptom-related pain relief. The indication for
      surgical management such as TURP and spinal cord decompression is depending on
      clinical symptoms from local progression and systemic disease.

PMID- 9563129
TI  - [Pain therapy and quality of life].
AB  - In the treatment of advanced hormone-resistant prostate cancer, the aim is an
      improvement in quality of life since treatment strategies are merely palliative
      and life cannot be prolonged. Therapy is based on medical pain relief for
      different aspects of pain without seriously affecting activity and quality of
      life. With respect to therapy of chronic pain, Germany can be regarded as a
      developing country. It is definitely in the interest of urological cancer
      patients that this situation will be finished.

PMID- 9563128
TI  - [Indications for nuclear medicine therapy in advanced prostate carcinoma].
AB  - For patients with advanced prostate cancer efficient therapy of painful bony
      lesions is the primary goal of interdisciplinary treatment strategies.
      Preservation of quality of life appears to be the main aim rather than
      prolongation of life. Apart from oral pain relief and local irradiation systemic
      treatment with radionuclides offers low-risk radiotherapeutic strategies for the
      palliation of painful, multifocal osteoplastic bone metastases. Depending on the
      radiopharmaceutical substance chosen response and reduction of pain are described
      in 65-80%. The duration of pain relief lasts between 6-12 weeks. During this time
      the morphine based medication can be reduced and in some cases withdrawn which
      positively effects quality of life. After improvement of myelosuppression
      treatment with radionuclides can be repeated. Patients have to be hospitalized
      for two days because of protection from radiation procedures.

PMID- 9563130
TI  - [The significance of prostate-specific antigen in after-care of prostate
      carcinoma].
AB  - Prostate specific antigen (PSA) is used in the follow-up of patients who
      underwent radical prostatectomy and radiotherapy or who have systemic disease.
      However, easy assessment and high diagnostic value of PSA should not lead to
      frequent and unnecessary testing. Following radical prostatectomy or radiotherapy
      intervals of 6 months appear to be sufficient whereas patients with metastatic
      disease should be followed symptom related.

PMID- 9563131
TI  - [Is gene therapy of advanced prostatic carcinoma on the verge of clinical
      application?].
AB  - Gene transfer strategies for prostate cancer may yield promising future
      perspectives. In this regard, gene modified tumor vaccines, suicide gene therapy
      and gene replacement of nonfunctioning tumor suppressor genes are of special
      interest. Clinical phase I and early phase II studies with gene modified vaccines
      have to demonstrate the clinical implication of these new therapeutic options.
      Apart from this approach the development of more efficient delivery systems for
      in vivo gene transfer is highly desirable.

PMID- 9563132
TI  - [Reconstruction of meatus/fossa navicularis using skin flap technique].
AB  - The author discusses the procedures for reconstruction of the meatus and fossa
      navicularis. The author describes four separate procedures for reconstruction
      using vascularized skin island. The choice of the procedure depends on the
      anatomy of the stricture as well as the anatomy of the redundancy of penile skin.

PMID- 9563133
TI  - [Fundamentals and basic principles of tissue transfer].
AB  - The advancements in tissue transfer techniques made recent years allow the
      reconstructive surgeon to view the whole body as a potential donor site. Now
      functional results, along with cosmetic results, can be considered as paramount
      in the thinking of the reconstructive surgeon. In the past, techniques of tissue
      transfer tended to be considered in ladder fashion with the surgeon applying
      techniques of transfer from simplest to "exotic" as opposed to considering
      optimal functional/cosmetic results. Now reconstructive surgeons routinely
      consider the "exotic" when it yields the best functional/cosmetic results. The
      basic that will be discussed in this chapter are designed to provide a platform
      from which GU reconstructive surgeon launches into more complex and imaginative
      procedures.

PMID- 9563134
TI  - [Development of tumor selection based on pathological stage in clinically
      localized prostate carcinoma].
AB  - Four hundred and eighty-eight radical retropubic prostatectomies (RRP) were
      performed on clinically localized prostate cancer at one institution within 5
      years (1992-1996). These were then analyzed regarding the migration of
      pathological tumor stages towards more localized stages. Within the observation
      period, the annual rate of RRP increased by 81% from 69 to 125 cases. The authors
      noted a decline in the occurrence of advanced tumor stages (65.0% to 39.2%) and
      small cancers (< 0.5 cc: 7.2% to 1.6%) and an increase in pathological T2 tumors
      (30.4% to 55.2%). The rate of positive surgical margins declined from 34.7% to
      12.8% (for all pathological stages). These data confirm trends which were
      observed in the USA with increasing detection and treatment of localized prostate
      cancer.

PMID- 9563135
TI  - [Plasma TGF-beta1 concentrations in patients with prostate carcinoma or benign
      prostatic hyperplasia].
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotrophic growth factor in
      carcinogenesis and regulars multiple cell functions. We wanted to evaluate the
      diagnostic meaning of TGF-beta 1 plasma levels in patients with a biopsy proven
      prostate cancer. The TGF-beta 1 blood level was analysed in 394 patients. In 242
      patients (group I) the blood was taken before any prostate manipulation and
      biopsy. The TGF-beta 1 plasma concentrations were almost similar in the group of
      patients with a prostate cancer (n = 157) and patients with a benign prostate
      hyperplasia (n = 85; 14,258 pg/ml versus 14,658 pg/ml, SD 10,516 pg/ml). In 152
      patients the blood was taken 6-12 months after radical prostatectomy (group II).
      There was no significant difference between the patients with a PSA-progress and
      without PSA-progress after. Our results suggest that TGF-beta 1 plasma levels can
      not be used to distinguish between patients with prostate cancer and benign
      prostate hyperplasia.

PMID- 9563136
TI  - [The VATER syndrome from the urologic viewpoint].
AB  - Duplications of the bladder is uncommon and rarely occurs as isolate anomaly. Two
      cases of complex malformations from the VACTERL-association are reported. The
      study of urogenital duplications in cases from the literature are described.

PMID- 9563137
TI  - [Bladder carcinoma. 2: Urinary diversion].

PMID- 9563138
TI  - Cryoablation of localized prostate cancer: neoadjuvant downsizing of prostate
      cancer with LH-RH analogue depot before cryosurgery.
AB  - Radical prostatovesiculectomy, radiation therapy, and complete androgen
      deprivation are acknowledged therapeutic concepts in the treatment of organ
      confined prostate cancer. With cryoablation of the prostate, minimal invasive
      therapy has become available since 1991. Improvements in cryotechnique and
      progress in transrectal high-resolution ultrasound permit thermo-induced damage
      to the whole gland to be curative. Downstaging of prostate cancer by hormone
      ablative therapy remains a controversial issue at this time, but the use of
      androgen ablation decreases the size of the prostate gland which facilitates
      cryosurgery and improves the results. The freezing equipment has a limited
      capacity, and in certain instances large gland volumes prevent adequate freezing
      of the prostate. Since percutaneous prostate cryosurgery leaves dead tissue in
      situ to be resorbed over time, downsizing reduces the amount of necrotic tissue
      to be resorbed, reducing the potential for complications, particularly abscesses.
      The use of androgen ablation also increases the deposition of fat in the area of
      the Denonvillier's fascia, making freezing of the rectum less likely during the
      procedure. In our study androgen ablative therapy was completed before performing
      cryosurgery in 26 of 43 patients (58%). The 17 patients not given androgen
      ablation therapy had gland volumes < 40 ml, tumor volumes < 3 ml, and no evidence
      of extracapsular tumor. The neoadjuvant therapy consisted of a 3- to 10-month
      course of leuprolide acetate combined with an antiandrogen.

PMID- 9563140
TI  - Complete androgen blockade versus chemical castration in advanced prostatic
      cancer: analysis of an Italian multicentre study. Italian Leuprorelin Group.
AB  - OBJECTIVES: In spite of a great amount of data, the hormonal treatment of
      advanced prostatic carcinoma (CaP) still remains controversial. As a relevant
      amount of dihydrotestosterone is present within the prostate tissue after
      castration, complete androgen blockade (CAB), with inhibition of the activity of
      both testicular and adrenal androgens, has been advocated as up-front treatment
      of advanced CaP. However, many controlled studies have failed to demonstrate a
      benefit for CAB in comparison with simple surgical or chemical castration. The
      present study was performed to bring additional data for a worldwide meta
      analysis of all phase III trials comparing castration and CAB. METHODS: This is a
      centrally controlled phase III study in which chemical castration with
      leuprorelin acetate depot was compared with leuprorelin plus flutamide in stage C
      and D CaP. Two hundred and forty-one eligible and evaluable patients with
      histologically proven CaP were recruited for the study (120 treated with
      castration and 121 with CAB). The diagnostic and staging workup consisted of
      blood chemistry, general condition assessment, prostate-specific antigen (PSA),
      abdominal sonography and computed tomography scan, and whole-body isotopic bone
      scan. End points of the study were survival, time to treatment failure, and time
      to progression. The patients were followed every 6 months with PSA and
      sonography. RESULTS: At a cut-off analysis performed in December 1996, when the
      mean follow-up period was 43.7 +/- (SD) 24.1 months, no statistical differences
      in terms of time to treatment failure, time to progression, and death rate could
      be detected. Also considering the common risk factors, such as basal PSA,
      haemoglobin, alkaline phosphatase, and Gleason score, the outcome did not show
      any clear advantage for CAB. CONCLUSIONS: This study appears to confirm that the
      advantages of first-line CAB in CaP are at best marginal. The final analysis will
      be performed when the follow-up period has reached 5-years, but it seems unlikely
      that the present results will change.

PMID- 9563141
TI  - Apoptosis in prostatic adenocarcinoma following complete androgen ablation.
AB  - OBJECTIVE: To analyze the cell death phenomenon in prostate cancer following
      complete androgen ablation. METHODS: The frequency and location of apoptotic
      bodies (ABs) were evaluated in haematoxylin and eosin stained sections of radical
      prostatectomy specimens from patients with invasive prostatic adenocarcinoma
      treated with neo-adjuvant endocrine combination therapy for 3 months before
      surgery. The results were compared with an untreated age- and stage-matched
      control group. RESULTS: Both in treated and untreated prostate tissue the AB
      frequency increased from normal prostate, through prostatic intraepithelial
      neoplasia, up to prostatic adenocarcinoma. The main location was in the cell
      layers adjacent to the stroma, their frequency decreasing towards the lumen. The
      frequency of ABs was higher in the treated prostate glands than in the untreated
      groups. The relative increase of the AB frequency in treated carcinomas as
      compared with untreated ones was lowest in tumours with a solid pattern,
      intermediate in the cribriform, and highest in the acinar pattern. CONCLUSIONS:
      Complete androgen ablation induces involution of prostate tissue mainly through
      the enhancement of apoptosis. This type of cell death is thought to play a major
      role and might be linked to specific changes in signal transduction mechanisms in
      response to hormonal withdrawal.

PMID- 9563139
TI  - Comparison of LH-RH analogue 1-month depot and 3-month depot by their hormone
      levels and pharmacokinetic profile in patients with advanced prostate cancer.
AB  - In an open, randomized phase II pharmacokinetic study conducted in Germany and
      Italy, a total of 42 patients with advanced or metastatic prostate cancer (PCa)
      were treated for 9 months with the luteinizing hormone-releasing hormone analogue
      (LH-RH-a) leuprorelin acetate depot in two different formulations. Fifteen
      patients received the 1-month depot and 27 patients received the newly developed
      3-month depot, containing 3.75 mg and 11.25 mg, respectively. In both groups,
      subcutaneous injections of leuprorelin acetate injected monthly or at 3-month
      intervals produced a complete down-regulation of the pituitary and led to
      persistent suppression of testosterone and dihydrotestosterone to the castrate
      range (< or = 50 ng/dl for testosterone) within the first month of treatment,
      which thereafter could be maintained over the entire observation period of 9
      months. In 10 patients, pretreatment with an antiandrogen for the prevention of
      clinical flare-up resulted in a slightly more profound and earlier drop in serum
      testosterone. The 3-month depot showed a higher median peak serum concentration
      (Cmax) of leuprorelin at 20.8 ng/ml than the 1-month depot at 10.7 ng/ml but,
      conversely, this did not influence the rise in serum testosterone levels. Cmax
      occurred at 3 h for the 3-month and at 1 h for the 1-month depot formulation.
      During the steady state, constant release could be detected, starting on day 3
      and day 7 for the 1-month and 3-month depot, respectively. A marked decrease in
      median prostate-specific antigen levels of 97.8% (1-month depot) and 96.6% (3
      month depot) compared with baseline was observed, indicating an objective
      clinical response for more than 80% of all patients in both arms. Based on
      European Organization for Research and Treatment of Cancer criteria, the best
      response in terms of complete/partial remissions and stabilization was comparable
      in the two arms at 86.7% (1-month depot) and 85.2% (3-month depot). 6.7% in the 1
      month group and 3% in the 3-month depot group showed progression of the disease.
      The most common side effects in both treatment groups were related to hormone
      deprivation. Both formulations of the potent LH-RH-a leuprorelin acetate were
      highly effective in the treatment of advanced PCa and led to comparable endocrine
      and clinical effects.

PMID- 9563142
TI  - Urinary kidney stone inhibitors. What is the news?
AB  - Supersaturation with respect to calcium salts (oxalate and phosphate) is the
      driving force leading to crystalluria and nephrolithiasis. High-molecular-weight
      urinary inhibitors are recently described molecules capable of altering the
      process of kidney stone formation. By inhibition of crystal nucleation, growth
      and aggregation and by inhibition of crystal interaction with tubular cells,
      these proteins efficiently prevent stone formation and retention in the urinary
      tract. But in spite of considerable efforts, characterization of these proteins
      is still under way. Besides the pathophysiology of risk factors for calcium salts
      supersaturation such as idiopathic hypercalciuria or hyperoxaluria, the renal
      involvement of protein inhibitors is the most exciting field in the comprehensive
      approach of nephrolithiasis, a disease that affects up to 10% of people in
      Western countries.

PMID- 9563143
TI  - Experimental partial ureteric obstruction in newborn rats. X. Renal function and
      morphology after unobstruction.
AB  - Partial obstruction of the left ureter was created in newborn rats. Unobstruction
      was performed after 2 or 7 days. The investigations were carried out at 9 weeks
      of age--under slight hydropenia to institute an element of stress. Unobstruction
      was successful. On the unobstructed side, there were nevertheless impairments as
      compared to controls: urine osmolality (-32%), free water reabsorption (-44%),
      potassium excretion (-34%), renal blood flow (-36%) and glomerular filtration (
      36%). On the intact contralateral side, tubular changes were the only signs of an
      attempt to compensate. Thus, consistent renal damage remained despite a very
      early unobstruction. Furthermore, the changes were similar to those we observed
      during long-term permanent obstruction. The injury seems to be established within
      a very short time and imitates the probable development seen in the affected
      fetus: after start of production, the urine is confronted by the preformed
      obstruction at the pyeloureteral junction. A high-pressure-prone system is built
      up and is not reversed, until the pelvis has become dilated and thus capable to
      buffer urinary flow peaks. Thereafter, no further deterioration occurs except in
      specific conditions. If clinically applicable, these observations implicate that
      there is no advantage with surgical intervention, even when performed early in
      fetal life, and there is no need for swift intervention, as the damage does not
      progress after its establishment. Most of the cases probably do not require
      surgery at all, unless pain, obvious functional impairment or urinary tract
      infection supervene.

PMID- 9563144
TI  - Prediction of urinary continence following radical prostatectomy.
AB  - The aim of this study was to assess the incidence of incontinence after radical
      prostatectomy and to identify the various factors that can predict urinary
      continence after radical prostatectomy. Urinary continence following a radical
      prostatectomy was evaluated in 175 consecutive patients who underwent surgery.
      Immediately after catheter withdrawal, on the 15th postoperative day, 66% of the
      patients were incontinent. Varying degrees of incontinence persisted in 53% of
      the cohort at 1 month postoperatively. Thirty-three, 12, 8 and 2% of the patients
      remained incontinent at respectively 3, 6, 9 and 12 months of follow-up. A number
      of possible pre- and peroperative factors which might predict the continence
      status were examined are related to it at subsequent intervals after the surgical
      intervention. Preservation of the neurovascular bundles, prior transurethral
      resection of the prostate, preoperative micturition disorders and age were
      significant contributors in the prediction of urinary incontinence after radical
      prostatectomy.

PMID- 9563145
TI  - Comparative study of therapeutic effect of dibenyline, finasteride, and
      combination drugs for symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVES: A prospective study was conducted in a community hospital in order to
      evaluate the therapeutic effect of dibenyline, finasteride, and a combination of
      the two drugs for symptomatic benign prostatic hyperplasia (BPH). METHODS: 190
      men suffering from severe prostatism entered this study. They were assessed by
      IPSS symptom score, digital rectal examination, transrectal sonography of the
      prostate, uroflowmetry and residual urine. The patients were randomly selected
      for medical treatment with dibenyline 10 mg b.i.d. (n = 71), finasteride 5 mg
      q.d. (n = 54), and a combination (n = 65). Clinical assessments were carried out
      before treatment and 3 and 6 months after starting treatment. Patients who could
      not complete the treatment and those with prostatic cancer were excluded from the
      final statistics. The quality of life after 6 months of treatment and side
      effects were also assessed. RESULTS: A total of 172 patients completed the
      treatment course and 153 patients completed the periodic clinical assessments.
      Improvement in IPSS was noted in all 3 groups of patients both at 3 and 6 months.
      The prostatic volume was found to decrease in the finasteride group and the
      combination group at 6 months by 24.3 and 10.5%, respectively. Maximal flow rate
      (Qmax) was significantly improved in the dibenyline and combination groups but
      not in the finasteride group at 3 months. At 6 months a significant increase in
      Qmax was noted in all groups with a mean increase of 1.4-1.8 ml/s. The quality of
      life after treatment was satisfactory in 71.9% of the dibenyline group, 70.4% of
      the finasteride group and 83.1% of the combination group. Side effects were
      higher in the dibenyline than the finasteride or combination group. The dropout
      rate was higher in the dibenyline group (15.5%) than in the finasteride (7.5%)
      and combination (4.6%) groups. After 6 months of treatment, some of the patients
      discontinued medication and symptom relapse was noted in 92.6% of the dibenyline
      group, 57.6% of the finasteride group, and 71% of the combination group.
      CONCLUSIONS: Medical treatment is effective in treating symptomatic BPH.
      Combination dibenyline and finasteride provides a weak synergistic clinical
      effect without additive side effects.

PMID- 9563146
TI  - IL-1ra versus IL-1 levels in prostatic fluid from prostatitis patients.
AB  - Recent papers reported that the balance between the production of IL-1ra and IL-1
      probably influences the regulation of host responses, the severity and
      prolongation of the inflammatory reaction in some diseases. Therefore, in our
      continuing investigation to clarify the significance of leukocytosis and its
      prolongation in prostatic fluid from prostatitis patients, we investigated
      whether low levels of IL-1ra versus IL-1 beta secreted in prostatic fluid were
      the cause of prolonged prostatitis, especially nonbacterial prostatitis (NBP). As
      a result of the present study, we concluded that a low level of IL-1ra in
      relation to that of IL-1 secreted in prostatic fluid is unlikely to cause
      prolongation of NBP for the following reasons: (1) IL-1 beta was detected in 5 of
      10 cases (50.0%), but was slightly elevated in only 2 cases (20.0%) at 14 and 17
      pg/ml; (2) the average IL-1ra level was not statistically low compared with that
      in prostatic fluid from acute bacterial prostatitis (ABP) patients who were cured
      promptly with antibiotics, and (3) in 5 cases of NBP in which IL-1 beta was
      detected, the average IL-1ra/IL-1 beta ratio was 118 which was comparable to or
      even higher than that in 3 ABP and 14 acute bacterial cystitis cases in which IL
      1 beta was detected and the ratios were 40 and 88, respectively.

PMID- 9563147
TI  - Coincidence of induratio penis plastica and erectile dysfunction.
AB  - There are still diverse management options in Peyronie's disease and diverse
      opinions about the coincidence of Peyronie's disease and erectile dysfunction
      (ED) as well. The connection between Peyronie's disease and ED has been proved by
      some articles, but on the other hand authors have refused this fact. We found ED
      in about 30% of our patients suffering from Peyronie's disease. We have
      investigated 61 patients with Peyronie's disease. A diagnostic pattern for
      evaluation of angulation and ED are proposed. The tunica albuginea plication
      technique was used in 35 patients with good results. In our investigation we
      cannot find any coincidence of Peyronie's disease with ED.

PMID- 9563148
TI  - The relationship between diabetes mellitus, impotence and veno-occlusive
      dysfunction in Peyronie's disease patients.
AB  - Peyronie's disease is an ill-defined condition that often leads to severe penile
      deformity and sometimes erectile dysfunction. Penile Doppler studies indicate
      veno-occlusive dysfunction as the principal cause of poor rigidity in Peyronie's
      disease patients. Diabetes mellitus is also a known cause of impotence and its
      prevalence tended to be higher in patients with Peyronie's disease. We evaluated
      143 patients with Peyronie's disease, also 92 impotent men (37 diabetic, 55
      nondiabetic) as control group. Penile vascular studies were performed on each
      group. Diabetes mellitus was also investigated in patients with Peyronie's
      disease. Veno-occlusive dysfunction was found as the main cause of impotence in
      both groups (81.1% in diabetic, 89% in nondiabetic control group and 88.8% in
      Peyronie's disease patients). In our study group the prevalence of diabetes
      mellitus tended to be higher than in the control population but it did not alter
      the ratio of veno-occlusive dysfunction and impotence in Peyronie's disease
      patients. We believe there is a close relationship between diabetes mellitus and
      Peyronie's disease, considering our high incidence. We also conclude that
      diabetes mellitus is not the main cause of impotence in patients with Peyronie's
      disease.

PMID- 9563149
TI  - Magnesium hydrogen carbonate natural mineral water enriched with K(+)-citrate and
      vitamin B6 improves urinary abnormalities in patients with calcium oxalate
      nephrolithiasis.
AB  - The influence of drinking magnesium hydrogen carbonate natural mineral water
      enriched with potassium citrate on urinary metabolic abnormalities was
      prospectively studied in 27 patients with recurrent calcium oxalate
      nephrolithiasis. The mean 24-hour urinary pH shifted from 6.34 to 6.93 (p <
      0.01), the mean urinary magnesium/urinary creatinine ratio rose from 0.47 to 0.67
      (p < 0.01), the mean urinary citrate/urinary creatinine ratio increased from 0.26
      to 0.35 (p NS), and the mean 24-hour urinary calcium decreased from 7.98 to 6.05
      mmol (p < 0.05). The effects of magnesium hydrogen carbonate natural mineral
      water enriched with potassium citrate were found to be favorable on urinary
      calcium, urinary magnesium/urinary creatinine ratio and urinary pH in patients
      with calcium oxalate nephrolithiasis.

PMID- 9563150
TI  - Acquired renal cystic disease and adenocarcinoma following renal transplantation-
      a current urologic perspective.
AB  - Two patients treated with chronic dialysis and renal transplantation developed
      acute hemorrhage from a native kidney. Bilateral native nephrectomy demonstrated
      acquired cystic disease and adenocarcinoma in each of the four kidneys. The
      etiology of acquired cystic kidney disease (ACKD) is unclear and its incidence
      increases with the duration of dialysis. ACKD patients have a propensity to
      develop adenomas and adenocarcinomas. The increased incidence of renal neoplasms
      in ACKD patients warrants careful radiologic monitoring of native end-stage
      kidneys in selected patients.

PMID- 9563151
TI  - Management of renal angiomyolipoma by selective arterial embolization.
AB  - 4 Patients with renal angiomyolipomas are presented. One of them had tuberous
      sclerosis with synchronous bilateral tumors. All the patients were symptomatic, 2
      of them with retroperitoneal hemorrhage. In all patients selective arterial
      embolization was performed. Permanent control of the symptoms was successful in 2
      patients. In 1 patient temporary resolution of the symptoms was observed, and a
      second embolization was required. Retroperitoneal bleeding in 1 patient continued
      and nephrectomy was undertaken.

PMID- 9563152
TI  - Malignant mesodermal mixed tumor of the ureter.
AB  - Malignant mesodermal mixed tumor comprised of epithelial and nonepithelial
      components is rarely encountered in the urological field. Only 6 cases of
      malignant mesodermal mixed tumor of the ureter have previously been reported in
      the literature. We recently encountered a 7th case of malignant mesodermal mixed
      tumor of the ureter and describe the case in detail. The etiology of malignant
      mesodermal mixed tumor is also discussed.

PMID- 9563154
TI  - Epididymal metastasis of a prostatic carcinoma.
AB  - We report the case of a 73-year-old patient who presented with a local recurrence
      of a prostatic carcinoma which had metastasized to the right epididymis. The
      histopathological examination of the resected tissue after transurethral
      resection of the prostate 8 years before revealed a pluriformal adenocarcinoma of
      the prostate, but the patient refused any kind of therapy at that time.

PMID- 9563153
TI  - Brain metastasis as a sole recurrence of prostate cancer after total
      prostatectomy.
AB  - Brain metastasis from prostate cancer is a rare clinical event. We present a case
      of prostate cancer with a solitary brain metastasis as a sole site of recurrence
      after total prostatectomy. To our knowledge, this is the third reported case of
      an isolated brain metastasis from prostate cancer.

PMID- 9563155
TI  - High-flow priapism leading to the diagnosis of lung cancer.
AB  - We report on a patient with spontaneous high-flow priapism. Magnetic resonance
      imaging showed a sacral tumor. Prior to tumor surgery, signs of lung cancer were
      found on chest X-ray. The diagnosis was confirmed by bronchoscopy. Priapism in
      this case can be explained either as a paraneoplastic symptom or as an isolated
      manifestation of cauda compression. Both are very uncommon reasons for priapism.

PMID- 9563156
TI  - Synchronous bilateral torsion of the appendix testis.
AB  - Bilateral torsion of testicular appendages is extremely uncommon. We present a
      rare clinical case of bilateral synchronous torsion of the hydatids of Morgagni.
      Clinical management was dictated by the clinical findings.

PMID- 9563157
TI  - Fournier's gangrene: viability monitoring of subcutaneously transported testis
      following extensive debridement by color-coded duplex sonography and nuclear
      magnetic resonance.
AB  - We report the case of a subcutaneously transposed testis after surgical
      depridement for Fournier's gangrene. Its viability was successfully monitored
      using color-coded duplex sonography and nuclear magnetic resonance.

PMID- 9563158
TI  - An experimental infection with classical swine fever virus in weaner pigs. I.
      Transmission of the virus, course of the disease, and antibody response.
AB  - The spread of Classical Swine Fever (CSF) virus (strain Lorraine), originally
      isolated in the first CSF infected herd of the 1993-1994 Belgian epizootic, was
      examined in an isolation unit with three adjacent pens and 15 weaner pigs per
      pen. Virus was introduced through experimental inoculation of one weaner pig in
      the middle pen (pen 2). The experimentally inoculated pig became viraemic 4 days
      post-inoculation (dpi) and the pen mates at 12 (n = 9) and 14 dpi (n = 5). The
      first viraemia in pens 1 and 3 was observed 18 dpi. Pigs were found to be
      seropositive in pens 1, 2, and 3 from 24, 20, and 22 dpi onwards, respectively.
      The reproduction ratio (R0) for the pigs in pen 2, estimated according to the
      martingale method, was 81.3 (s.e. = 109.54). The rate ratio (Cox proportional
      hazard) of the first pigs to become viraemic in pen 3 (airborne contact plus
      contact via contaminated clothing and footwear with pen 2) versus pen 1 (airborne
      contact with pen 2 only) was 1.60 (P = 0.3342). Thus, the additional contact of
      contaminated clothing did not affect transmission of the CSF virus. The survivor
      function (Kaplan-Meier survival analysis) did not significantly differ per pen.
      The time from first detection of virus in plasma to death was not significantly
      different between pens. The mean rectal temperature of pigs in a pen increased 3
      to 4 days prior to detection of virus. The proportion of seropositive pigs per
      pen (p) from the day the first weaner pig in a pen became viraemic (dpf) was
      examined as a function of time with a logistic regression model. The model
      parameter estimates did not differ between pens. Hence, the data from the three
      pens were pooled. The regression equation of the seroprevalence over time for the
      pooled data was p = 1/[1+e(4.65-0.39 *dpf)].

PMID- 9563159
TI  - An experimental infection with a classical swine fever virus in weaner pigs. II.
      The use of serological data to estimate the day of virus introduction in natural
      outbreaks.
AB  - In a companion paper a logistic regression model of seroprevalence over time was
      developed on the basis of data obtained during an experimental infection of
      weaner pigs with classical swine fever (CSF) virus. The model was applied to
      seroprevalence data from three outbreaks of the 1993-1994 epizootic to test
      whether the model could predict correctly the day of virus introduction into the
      herd. It was concluded that the logistic regression model has potential as a tool
      to estimate in retrospect the day CSF virus was introduced into a pig herd, which
      in turn may assist in identification of risk factors implicated in the further
      spread of the disease.

PMID- 9563160
TI  - Major immunogenic proteins of phocid herpes-viruses and their relationships to
      proteins of canine and feline herpesviruses.
AB  - The immunogenic proteins of cells infected with the alpha- or the gamma
      herpesvirus of seals, phocid herpesvirus-1 and -2 (PhHV-1, -2), were examined in
      radioimmunoprecipitation assays as a further step towards the development of a
      PhHV-1 vaccine. With sera obtained from convalescent seals of different species
      or murine monoclonal antibodies (Mabs), at least seven virus-induced
      glycoproteins were detected in lysates of PhHV-1-infected CrFK cells. A
      presumably disulphide-linked complex composed of glycoproteins of 59, 67 and
      113/120 kDa, expressed on the surface of infected cells, was characterized as a
      major immunogenic infected cell protein of PhHV-1. This glycoprotein complex has
      previously been identified as the proteolytically cleavable glycoprotein B
      homologue of PhHV-1 (14). At least three distinct neutralization-relevant
      epitopes were operationally mapped, by using Mabs, on the glycoprotein B of PhHV
      1. Among the infected cell proteins of the antigenically closely related feline
      and canine herpesvirus, the glycoprotein B equivalent proved to be the most
      highly conserved glycoprotein. Sera obtained from different seal species from
      Arctic, Antarctic, and European habitats did not precipitate uniform patterns of
      infected cell proteins from PhHV-1-infected cell lysates although similar titres
      of neutralizing antibodies were displayed. Thus, antigenic differences among the
      alphaherpesvirus species prevalent in the different pinniped populations cannot
      be excluded. PhHV-2 displayed a different pattern of infected cell proteins and
      only limited cross-reactivity to PhHV-1 at the protein level was detected, which
      is in line with its previous classification as a distinct species, based on
      nucleotide sequence analysis, of the gammaherpesvirus linenge. A Mab raised
      against PhHV-2 and specific for a major glycoprotein of 117 kDa, cross reacted
      with the glycoprotein B of PhHV-1. The 117-kDa glycoprotein could represent the
      uncleaved PhHV-2 glycoprotein B homologue.

PMID- 9563161
TI  - Multiple endocrine neoplasias in a dog: corticotrophic tumour, bilateral
      adrenocortical tumours, and pheochromocytoma.
AB  - In a 10-year-old ovariohysterectomized standard Schnauzer, the finding of
      dexamethasone-resistant hypersecretion of cortisol, the results of computed
      tomography, and elevated plasma concentrations of ACTH suggested the presence of
      both adrenocortical tumour and pituitary-dependent hyperadrenocorticism. The dog
      made an uneventful recovery after bilateral adrenalectomy and remained in good
      health for 31/2 years with substitution for the induced hypoadrenocorticism. Then
      the enlarged pituitary caused neurological signs and eventually euthanasia was
      performed. The surgically excised right adrenal contained a well-circumscribed
      tumour of differentiated adrenocortical tissue and in the left adrenal there were
      two adrenocortical tumours and a pheochromocytoma. The unaffected parts of the
      adrenal cortices were well developed and without regressive transformation. At
      necropsy there were no metastatic lesions. The cells of the pituitary tumour were
      immunopositive for ACTH and had characteristics of malignancy. The present
      combination of corticotrophic tumour, adrenocortical tumours, and
      pheochromocytoma may be called 'multiple endocrine neoplasia' (MEN), but does not
      correspond to the inherited combinations of diseases known in humans as the MEN-1
      and the MEN-2 syndromes. It is suggested that the co-existence of
      hyperadrenocorticism and pheochromocytoma may be related to the vascular supply
      of the adrenals. Some chromaffin cells of the adrenal medulla are directly
      exposed to cortical venous blood, and intra-adrenal cortisol is known to
      stimulate catecholamine synthesis and may promote adrenal medullary hyperplasia
      or neoplasia.

PMID- 9563162
TI  - Concentrations of sulfadoxine and trimethoprim in plasma, lymph fluids and some
      tissues 24 h after intramuscular administration to Angora goats.
AB  - This study was carried out to determine the concentrations of sulfadoxine and
      trimethoprim in plasma, lymph, and some tissues in goats after administration of
      a single recommended therapeutic dose. Five healthy, adult Angora goats were
      used. The drug combination, containing 200 mg sulfadoxine and 40 mg trimethoprim
      per millilitre, was given as a single IM injection at the recommended dose level,
      15 mg/kg body weight for sulfadoxine and 3 mg/kg body weight for trimethoprim.
      The goats were slaughtered 24 hours after drug administration and samples were
      taken from liver, bone marrow, pelvic limb muscles, hepatic, thoracic duct, and
      the pelvic limb lymph fluids for analysis of drug concentrations by HPLC. The
      concentrations of trimethoprim in bone marrow, liver, pelvic limb muscles,
      hepatic lymph, the pelvic limb lymph, and thoracic duct lymph were found to be 6,
      5, 4, 2, 5 and 15 times higher than those of plasma, respectively. Although the
      sulfadoxine concentrations in bone marrow, pelvic limb muscles, and liver were 2,
      3 and 2 times higher than the plasma concentrations, respectively, the
      sulfadoxine concentrations in hepatic lymph, the pelvic limb lymph, and thoracic
      duct lymph were lower than those of plasma. The results show that the
      trimethoprim concentrations in lymph fluids were quite similar to those in
      tissues. However, the sulfadoxine concentrations in lymph fluids were different
      in each tissue.

PMID- 9563163
TI  - Effects of endobronchial challenge with Actinobacillus pleuropneumoniae serotype
      9 of pigs vaccinated with inactivated vaccines containing the Apx toxins.
AB  - The efficacy of two inactivated vaccines containing the Apx toxins of
      Actinobacillus pleuropneumoniae (Hemopig, Biokema, Lausanne, Switzerland and
      Porcilis App, Intervet, Boxmeer, the Netherlands) was determined. Ten pigs were
      vaccinated twice with Hemopig and eight pigs with Porcilis App. Ten control
      animals were injected twice with a saline solution. Three weeks after the second
      vaccination, all pigs were endobronchially inoculated with 10(5) colony-forming
      units (CFU) of an A. pleuropneumoniae serotype 9 strain. Increased respiratory
      rate and/or fever were observed in all vaccinated and control pigs after
      challenge. One pig of the Hemopig group and of the Porcilis App group died,
      whereas all pigs of the control group survived the challenge. Surviving pigs were
      killed at 7 days after challenge. The mean percentage of affected lung tissue was
      34% in the control group, 16% in the Hemopig group, and 17% in the Porcilis App
      group. A. pleuropneumoniae was isolated from the lungs of all 10 control animals,
      from 7 of the 10 animals vaccinated with Hemopig and from 5 of the 8 animals
      vaccinated with Porcilis App. The mean bacterial titres of the caudal lung lobes
      were 1.4 x 10(6) CFU/g in the control group, 1.7 x 10(3) CFU/g in the Hemopig
      group, and 4.8 x 10(3) CFU/g in the Porcilis App group. In both vaccinated groups
      the mean number of days with dyspnoea, the mean number of days with fever, the
      mean percentage of affected lung tissue, and the mean bacterial titre in the
      caudal lung lobes were significantly lower than in the control group. Significant
      differences between the two vaccinated groups were not observed. It was concluded
      that both vaccines induced partial protection.

PMID- 9563164
TI  - Anthelmintic efficacy of oxibendazole against some important nematodes in dogs
      and cats.
AB  - The anthelmintic efficacy and safety of the oxibendazole component in a
      combination oxibendazole-niclosamide paste were investigated in dogs and cats and
      in litters of pups with naturally acquired nematode infections. A single dose of
      15 mg oxibendazole/kg body weight given to 70 dogs and to 29 cats reduced faecal
      worm egg counts (EPG) by 97.6% for Toxocara canis, 95.7% for Trichuris vulpis,
      94.6% for Ancylostoma caninum, and 100% for Toxascaris leonina. In cats, 96.7%
      efficacy was demonstrated against Toxocara cati. In a second trial, 119 pups in
      22 litters were treated with the same dosage at 2, 4, and 6 weeks of age. After
      treatment on two consecutive days, 95% of the pups did not shed T. canis eggs,
      compared with 85% after only a single treatment. Side effects were rare and only
      recorded in young animals. A 2-day treatment schedule is recommended for unweaned
      pups.

PMID- 9563165
TI  - Atrial fibrillation associated with central nervous symptoms and colic in a
      horse: a case of equine cardiomyopathy.
AB  - A 18-year-old Dutch Warmblood mare was referred for colic. Upon arrival,
      lethargy, blindness, head pressing, ataxia, and circling were the main clinical
      signs. On rectal examination a hard mass and oedema around the cranial mesenteric
      artery were palpated. Plasma liver enzyme activities and the ammonia level were
      elevated. Atrial fibrillation with a pulse frequency of 36-52 beats per minute
      was noticed. On both sides a holosystolic murmer with the maximum intensity on
      the right side could be auscultated. Postmortem examination revealed eccentric
      hypertrophy of the right atrium and a pale spotted myocardium, most prominently
      of the right ventricle, with secondary venous congestion of the azygos and
      mesenteric veins. The liver changes were indicative of chronic congestion.
      Despite the normal pulse rate, it appeared that congestive heart failure due to
      cardiomyopathy, was responsible for the presenting symptoms of this patient.

PMID- 9563166
TI  - Physiological levels of C-reactive protein in normal canine sera.
AB  - This study was undertaken to investigate whether the level of C-reactive protein
      (CRP) in the serum of dogs undergoes physiological variation, using 10 normal
      Beagle dogs (5 males and 5 females), 1-2 years old, maintained in a healthy
      condition in a controlled environment. The CRP concentration in the sera
      collected seven times each day at intervals of approximately 3 h ranged from 0.8
      to 16.4 micrograms/ml (mean 5.06 +/- 3.60) in one experiment and from 0.8 to 14.0
      micrograms/ml (mean 4.50 +/- 2.80) in a second experiment. On examining the 24-h
      variations in the concentration of CRP in serum, neither consistent changes nor a
      definite pattern of circadian rhythm was detected. During 28 days observation,
      only very slight changes, which seemed attributable to analytical errors, were
      seen in any of the dogs, except one. The concentration of CRP in the serum during
      the 28 days ranged from 0.8 to 22.6 micrograms/ml (mean 3.65 +/- 1.40). The
      concentrations underwent no significant variations in individual dogs, but
      significant differences were found between the dogs (p < 0.01).

PMID- 9563167
TI  - The disposition kinetics of albendazole following the administration of single
      and divided doses to cattle and buffalo.
AB  - Concentrations of albendazole sulphoxide and its sulphone metabolite in plasma in
      cattle and buffalo were measured by high-performance liquid chromatography after
      single and divided intraruminal administration of albendazole at the recommended
      nematocidal and fasciolicidal dose rates of 7.5 and 15.0 mg/kg body weight,
      respectively. No significant differences in the plasma concentrations of the
      metabolites or their pharmacokinetic parameters were observed between cattle or
      buffalo at either dose rate. Pharmacokinetic analysis and the disposition curve
      of the metabolites indicated increased uptake of the drug in both cattle and
      buffalo when the same total amount of the drug was given in divided doses
      compared to a single dose (p < 0.05). The divided dose schedules of
      administration could possibly be exploited to extend the life of the available
      benzimidazole anthelmintics.

PMID- 9563168
TI  - Sedative and analgesic effects of medetomidine in beagle dogs infected and
      uninfected with heartworm.
AB  - The sedative and analgesic effects of medetomidine were evaluated in heartworm
      infected (HW+) and uninfected (HW-) beagle dogs by intravenous (IV) and
      intramuscular (IM) administration of 30 micrograms/kg and 40 micrograms/kg doses,
      respectively. Posture, response to noise and the pedal reflex were monitored. A
      procedure for mock radiographic positioning was performed to evaluate its overall
      clinical use. Observation times were 0, 15, 30, 60, 90, 120 and 180 min. In
      addition, the times from injection until the dog could not stand on its feet
      (down time), from lateral to sternal recumbency (sternal recumbency time), and
      from sternal recumbency to rising again (rising time) were also noted.
      Medetomidine produced rapid sedation and analgesia by both routes. Down times for
      the IM and IV routes were similar, which verified the manufacturer's recommended
      doses. The HW+ dogs had shorter down times, probably owing to increased blood
      flow to the brain caused by adrenergic alpha-2 activity. Sternal recumbency and
      rising times did not differ between the groups, suggesting a similar metabolism.
      Sedation and analgesia were adequate for performing the procedure in all dogs. HW
      dogs showed less resistance to handling during the procedure than HW+ dogs.
      Overall, medetomidine seems to be a suitable agent for short-term chemical
      restraint in dogs, even with subclinical heartworm infestation.

PMID- 9563169
TI  - Catecholamine and cortisol responses of horses to incremental exertion.
AB  - The responses of the plasma concentrations of catecholamines and cortisol in
      horses to varied relative intensities of exertion were examined. The plasma
      concentrations of cortisol, epinephrine and norepinephrine increased
      significantly (p < 0.05) with exertion. The plasma cortisol concentrations at
      relative work intensities of 48.3% +/- 1.4%, 82.3% +/- 2.0% and 99.6% +/- 0.4% of
      VO2max were 114%, 124%, and 126%, respectively, of those at rest, whereas the
      plasma epinephrine concentrations were 239%, 772% and 3483%, and the
      norepinephrine concentrations were 138%, 255%, and 1121% of the values at rest.
      There was a significant (p < 0.0001) relationship between the plasma epinephrine
      and norepinephrine concentrations. The blood lactate concentration and the plasma
      epinephrine and norepinephrine concentrations were significantly (p < 0.0001)
      related, as were the relative work intensity (%VO2max) and the plasma epinephrine
      and norepinephrine concentrations. The relationships between the plasma cortisol
      concentration and work intensity or blood lactate concentration were not
      significant (p > 0.05). This study demonstrates a relationship between work
      intensity and indicators of adrenal medullary and sympathetic activity during
      brief exertion in horses.

PMID- 9563171
TI  - The chronic toxicity of inorganic mercury in goats: clinical signs,
      toxicopathological changes and residual concentrations.
AB  - Chronic mercury toxicity was induced in goats by administering mercuric chloride
      at 100 micrograms/ml in deionized drinking water offered ad libitum for 90 days.
      Toxic signs of gastrointestinal disturbances and renal dysfunction developed from
      43 days onwards without any mortality. The toxicity also induced nephrosis and
      tubular nephritis; centrilobular necrosis of liver; mild to moderate necrosis in
      spleen, intestine and lymph node; Zenker's degeneration of cardiac muscles;
      exudative pneumonia; and pial congestion, oedema and vacuolation in the brain. In
      addition, hyperaemia, oedema and tissue haemorrhages were evident in most of the
      organs. The kidneys contained the largest residues of mercury, followed by liver,
      spleen, intestine, lymph node, skeletal muscles, lungs, heart, brain and the
      omental fat. The intensity of the cytotoxic changes in the various organs was
      proportional to the amount of mercury accumulated.

PMID- 9563170
TI  - A comparison of the adrenal cortical response to ACTH stimulation in Angora and
      non-Angora goats.
AB  - The adrenal cortex is believed to be implicated in the high incidence of abortion
      in the Angora goat. Stimulation testing with adrenocorticotrophic hormone (ACTH)
      was used to assess the adrenal cortical function in 5 Angora does from herds with
      a history of abortion and 5 non-Angora does. An acute test involving a single
      intramuscular (i.m.) injection of 0.25 mg of synthetic ACTH was given during
      anoestrus, at mid-oestrus, on day 90 and on day 120 of gestation. Blood samples
      were collected from the jugular vein at 30 min intervals for 1 h before and 5 h
      after injection. Cortisol concentrations rose within 30 min and returned to
      baseline values within 3.5 h. Cortisol production was lower (p < 0.01) in the
      pregnant state compared to the non-pregnant state in both groups. Production of
      cortisol was consistently lower (p < 0.05) in the Angora does compared to the non
      Angora does during anoestrus and pregnancy and marginally so at mid-oestrus. A
      chronic stimulation test involving once daily injections of 0.5 mg of a depot
      form of ACTH i.m. for 7 days commencing on day 90 of pregnancy was also
      conducted. Cortisol concentrations rose to reach a peak on the third day of
      treatment in both groups. The values then declined in the Angora does despite
      continued ACTH treatment, while those for the non-Angora does exhibited a second
      peak. During and following this treatment, two non-Angora does delivered live
      kids (day 95, day 120). Out of 7 Angora pregnancies, one Angora doe aborted two
      dead fetuses at day 116. No significant difference in the cortisol response in
      the acute test was detected between the animals that aborted and their respective
      cohorts, but the two non-Angora does that aborted had significantly lower
      cortisol concentrations during depot ACTH administration. Progesterone and
      oestradiol levels did not differ between Angora and non-Angora animals during
      pregnancy or on the test days. The results suggest that the steroidogenic
      response of the adrenal cortex to ACTH stimulation is significantly less in
      Angora does with a history of abortion than it is in non-Angora does and support
      the view that the Angora goat would make a more limited adrenal cortical response
      to a stressful occurrence during pregnancy.

PMID- 9563172
TI  - Detection of challenge virus in fetal tissues by nested PCR as a test of the
      potency of a porcine parvovirus vaccine.
AB  - To estimate the potency of a porcine parvovirus (PPV) vaccine, three vaccinated
      and three non-vaccinated pregnant gilts were infected with PPV and the
      distribution of the virus was studied in the tissues of their 51 fetuses. Virus
      detection was attempted using haemagglutination (HA) and immunofluorescence (IF)
      assays, as well as by standard (single) and nested polymerase chain reactions
      (PCR). None of the detection methods yielded positive results when used to test
      for the presence of virus in suspensions of organs from the fetuses from the
      vaccinated gilts. However, the virus was detected in the fetuses from non
      vaccinated gilts as follows: HA was positive in 14 cases out of 23 (60.8%), IF in
      16/23 (69.5%), standard PCR in 12/20 (60%), and the nested PCR in 19/23 (82.6%).
      Although the correlation among the results of various methods of virus detection
      was rather close (r < 0.83), the sensitivity of the nested PCR was the highest,
      both when testing dilutions of PPV and when analysing the fetal organs. The
      nested PCR therefore provides a reliable approach for studies of virus
      distribution in fetal organs, with special reference to potency tests on
      vaccines.

PMID- 9563173
TI  - [Agitating is better than lamenting].

PMID- 9563174
TI  - [Bungee jumping. From a test of male courage to leisure fun of the "Dangerous
      Sports Club"].

PMID- 9563175
TI  - [Incidence of injuries and prevention in inline skating].

PMID- 9563176
TI  - [Effect of infrapatellar ligament bandages on the innervation behavior of knee
      stabilizing muscles].

PMID- 9563177
TI  - [New approbation law and orthopedics].

PMID- 9563178
TI  - [Extracorporeal shockwave therapy in epicondylitis humeri ulnaris or radialis--a
      prospective, controlled, comparative study].
AB  - AIM OF THE STUDY: Has extracorporal shockwave therapy in chronic golfer's elbow
      comparable results as in tennis elbow? METHOD: 30 patients for extracorporal
      shockwave therapy who suffered from chronic medial epicondylitis (group I) and 30
      patients with persistent tennis elbow (group II) received 500 impulses of 0.08
      mJ/mm2 three times at weekly intervals. The final follow-up examination was done
      after 24 weeks. RESULTS: Significant differences in relief of pain and
      improvement of function were observed in favour of group II. Good or excellent
      outcome was found in only 27% for the epicondylitis humeri ulnaris, but in 60%
      for epicondylitis humeri radialis. CONCLUSION: The indication for extracorporeal
      shock-wave therapy in medial epicondylitis must be questioned.

PMID- 9563180
TI  - [Results of mobilization under anesthesia in adhesive capsulitis in relation to
      stage of the disease].
AB  - PROBLEM: Mobilisation under anaesthesia is a well approved method for the
      treatment of idiopathic adhesive capsulitis, the best time to perform the
      mobilisation, however, is difficult to define. MATERIAL AND METHODS: Thirty-nine
      patients who had been treated with mobilisation under anaesthesia for idiopathic
      adhesive capsulitis stage II or III were examined at an average follow-up time of
      3.4 years. RESULTS: This therapy failed in 10.3% of the patients. There were no
      differences in the follow-up results between both groups of patients, limitations
      in the range of motion remained in 20% of all patients. At follow up the average
      CONSTANT Score of the stage II patients was 86.8, that of the stage III patients
      was 89.9 points. However, manipulation under anaesthesia showed a significantly
      better influence on the course of the disease in patients with stage III than in
      patients with stage II adhesive capsulitis. CONCLUSION: Mobilisation under
      anaesthesia is a successful therapy in adhesive capsulitis stage III, but should
      be performed in adhesive capsulitis stage II only in cases of decreasing pain in
      which the limitation in the range of motion is the main symptom.

PMID- 9563179
TI  - [Outcome of endoscopic subacromial decompression operation in tendinitis and
      partial rupture of the rotator cuff].
AB  - AIM OF THE STUDY: The series of this article compares 148 patients with chronic
      tendinitis (group I) and 28 patients with significant partial-thickness tears
      (group II) of the rotator cuff managed with arthroscopic debridement and
      acromioplasty. METHODS: All patients were evaluated by an independent observer
      with a mean follow-up of 26.5 (12-51) respectively 23.4 (12-50) months using the
      Constant-score, the ASES-score and a visual analog scale. The mean age in group I
      was 48.5 (25.4-71) and in group II 56.1 (33.2-80.6) years. RESULTS: In group I
      127 patients (86%) and in group II 17 patients (62%) were satisfied at latest
      follow-up (p < 0.05). Concerning the exclusively subjective ASES-score with a
      maximum of 100 points group I had an average of 78.8 and group II of 61.6 points
      (p = 0.0019). According to the criteria of Constant group I scored with a mean of
      81 points for the operated shoulder and 91.6 points for the non-operated side and
      group II with either 65.2 points and 89.9 points (p = 0.0036). CLINICAL
      RELEVANCE: Recognizing these results a thorough activity-related preoperative
      discussion with the patient about the treatment options for significant partial
      thickness cuff ruptures should be performed.

PMID- 9563181
TI  - [Follow-up and ultrasound-controlled early treatment of hip dysplasia].
AB  - PROBLEM: The reliability of ultrasound of the hip is examined by the courses of
      mature and physiologically immature hips. The results of sonographically
      controlled therapy of the congenital dysplasia of the hip are investigated.
      METHOD: 470 children out of a hip-screening program could be controlled at least
      one more time clinically and by ultrasound. X-rays were taken at the end of
      treatment in children who were treated by an abduction device. The sonographical
      and radiological results were compared and grafically presented. RESULTS: None of
      570 matured hips deteriorated. 88% of the physiologically immature hips matured
      spontaneously while 12% got a cast because of unsatisfactory development. 68
      pathological hips improved soon under therapy in an abduction device applied a
      few days after birth; they reached the borderline of 60 degrees at the maximum
      age of 80 days. X-ray examinations at the end of therapy showed normal acetabular
      indices in all cases. Six of 22 girls showed deterioration of the acetabular
      indices in further x-ray controls at the age of one year. CONCLUSION: Even in
      successful therapy of the congenital dysplasia in the newborn hip x-ray
      examinations are highly recommended to recognize deteriorations and to initiate
      another therapy if neccessary.

PMID- 9563182
TI  - [Recurrent Perthes disease in a 6-year-old boy].
AB  - Two episodes of avascular necrosis in the same femoral capital epiphysis have
      been reported in Gaucher's disease and in six cases of Legg-Calve-Perthes
      disease. The present case report is an additional example of a recurrent
      avascular necrosis in a six years old boy two years after complete healing of the
      first occurrence had been documented clinically and radiologically.

PMID- 9563183
TI  - [Current aspects of surgical management of patellar dislocation in the growth
      period with special reference to Goldthwait surgery].
AB  - RESEARCH QUESTION: The Goldthwait procedure is an operative treatment method for
      patellar dislocation in children which respects the growth plate. The aim of the
      study was to analyse the long term results of this procedure. METHODS: The
      results of 36 knees (26 children) operated on because of patellar dislocation
      according to the Goldthwait technique alone or in combination with other
      procedures (Krogius, patellar fixation) between 1941-1991 at Balgrist Clinic were
      analysed. Therefore, we used an own score. RESULTS: After a mean follow-up of 16
      years (1.5 to 51 years) we found in 77.8% of the cases good and very good
      subjective results, and in 63.9% good and very good objective results. A
      recurrence of dislocation occurred in 36.1% of the cases. In 76.9% of these cases
      a reoperation was performed, of which only one case led to an acceptable final
      result. The operation results were unsatisfactory in the presence of condylar
      dysplasia with an angle of more than 160 degrees. The age at the time of surgery
      and the degree of patellar dysplasia had no effect on the outcome. The success
      was increased through the use of the Goldthwait procedure in conjunction with
      other techniques. Pathologic leg axis or severe arthrosis did not occur.
      CONCLUSION: In absence of significant condylar dysplasia the Goldthwait procedure
      combined with other techniques provides acceptable results. The technique alone
      is less efficient.

PMID- 9563184
TI  - [Protrusion of a calcified cervical intervertebral disk in a 5-year-old boy].
AB  - Herniation of the calcified nucleus pulposus is a complication of intervertebral
      disc calcification. The herniated nucleus pulposus may assume an intraspinal
      location which may lead to cord compression and produce alarming neurological
      symptoms and radiographic images. Surgical intervention is, however, rarely
      necessary as complete resorption of the calcified disc material will generally
      occur. We report the case of a five years old boy with the symptoms of an acute
      tortcollis, radiographs of the cervical spine revealed calcification of C5/C6
      intervertebral disc and MRI narrowing of the spinal canal. With conservative
      treatment his symptoms resolved within three weeks, three months later X-rays and
      MRI showed complete resolution of the calcification and herniation.

PMID- 9563185
TI  - [Diagnosis of hip prosthesis loosening--sensitivity of clinical parameters].
AB  - AIM: In order to establish a strategy for early diagnosis of aseptic loosening of
      total hip arthroplasty (THA) physical examination, patient's assessment and
      radiographs were analysed. METHOD: Pain, self assessment, physical examination
      and mobility were examined according to a standard examination protocol in 428
      hips of 297 patients after cementless total hip arthroplasty (THA). These
      findings were compared with the radiographic finding of the hip. Sensitivity and
      specifity of objective and subjective parameters were analysed. RESULTS: The
      clinical outcome of THA's is assessed by pain and physical examination. Nearly
      all hip scores are based on these parameters. In this study sensitivity and
      specificity of all parameters analysed were unsatisfactory compared with the
      radiographic finding. Although we found some correlations between clinical and
      radiological data, clinical data alone are not sufficient for exclusion of THA
      loosening, especially for loosening of the acetabular component, as there was no
      clear distinction between the group of radiographically loosened (43 acetabular
      cups and 4 stems) and intact endoprostheses. CONCLUSION: We conclude, that
      physical examination and pain history are not sufficient to exclude loosening of
      cementless THA's. Radiographic examination is essential for the assessment of
      THA's, even in painfree patients.

PMID- 9563186
TI  - [Modified intracorporeal lithotripsy for cement removal in hip prosthesis
      exchange operations--experimental principles].
AB  - INTRODUCTION: Particularly problematic in total hip revision arthroplasty is the
      cement removal out of the depth of the femoral canal; it is also costly in time
      and effort. The extracorporal shock wave lithotripsy proved to be an unsuitable
      method. With the present paper we proved experimentally a newly developed
      endoscopically controlled modified intracorporal lithotripter (Swiss Orthoclast)
      for the removal of bone cement. METHODS: We tested the efficiency on standardized
      cement specimens of different manufacturers in vitro. We compared both
      conventional removing techniques with mallet and chisel and a pneumatically
      powered chisel with formalin fixed human femora. During these experiments we
      measured the intrafemoral pressure distally to the cement layer. RESULTS: We
      achieved a high energy (max. 450 mJ) and a very effective fragmentation of the
      cement (40 mg fragments calculated on the single impulse of 350 mJ). The
      endoscopic control ensures a safe control of the cement removal even in the depth
      of the femoral canal. No bone damage occurred macroscopically and radiologically.
      No heat or toxic products developed. Using the Swiss Orthoclast the intrafemoral
      pressure was the lowest possible (7 mbar). Even with hammer and chisel or the
      pneumatically powered chisel the pressure was too low (max. 55 mbar with mallet
      and chisel) to cause a fat embolic syndrome. CONCLUSION: As a result of these
      experiments we started with clinical trials (with permission of the Ethic
      commission) to evaluate the practicability of the modified intracorporal
      lithotripter (Swiss Orthoclast) for cement removal.

PMID- 9563187
TI  - [Augmentation of VDS(ventral derotation spondylodesis) by double rod
      instrumentation. A critical analysis of 2-to-4-year outcomes].
AB  - OBJECTIVES: In order to evaluate the benefits of the doublerod-VDS in the
      operative treatment of scoliosis the midterm results were critically analysed
      with specific respect to primary stability. METHODS: 24 patients with either
      idiopathic or neuromuscular curves were treated with the Doublerod-VDS. In some
      cases a singlerod instrumentation had to be carried out in the cranial fusion
      area due to too small vertebrae (Hybrid-VDS). Patients with thoracic curves were
      ambulated without any external support, the thoracolumbar curves were ambulated
      in a light, semirigid vest for a few months. All data including early and late
      complications were collected prospectively and a thorough radiometric analysis
      was carried out. RESULTS: Fusion was mostly carried out from end- to end
      vertebra. The correction of the idiopathic curves averaged 60.2% (preoperative
      Cobb angle 67.3 degrees) with a loss of correction of 5.2 degrees. In the
      neuromuscular curves the average correction was 61.1% (preoperative Cobb angle
      99.8% degrees) and the average loss of correction 4.2 degrees. There was no
      kyphogenic effect noted. In 6 cases a rod fracture was observed, in 4 cases the
      fracture occurred within the singlerod instrumentation in hybrid-VDS. Two of
      these patients developed a pseudarthrosis with loss of correction but without any
      symptoms. CONCLUSIONS: The hybrid-VDS does not offer any advantages compared to
      the Zielke-VDS. However, the doublerod-VDS in thoracic curves is primary stable
      and does not require any external support postoperatively. In thoracolumbar
      curves a light vest is suggested for the first postoperative months during day
      time.

PMID- 9563189
TI  - [Comparison of functional outcome in implantation of Natural Knee knee prostheses
      with and without patellar resurfacing].
AB  - PROBLEM: Despite the great progress in knee arthroplasty made within the previous
      decade the problem of patellar resurfacing is still unsolved. MATERIAL AND
      METHODS: In a retrospective matched-pairs study in 62 patients with Natural Knee
      endoprostheses including one group with and another without patella resurfacing
      were compared. Results were assessed according to the American Knee Society Score
      and the patients subjective assessments. RESULTS: At an average follow-up time 2
      years there were no differences in the clinical findings and the patients
      subjective opinions between both patient groups. However, patients with
      rheumatoid arthritis and patella resurfacing showed significantly better results
      in both categories than those rheumatoid patients without patella resurfacing.
      CONCLUSION: Summing our results up we cannot give a general advise towards the
      use of patella resurfacing in knee replacements. In patients with severe
      arthrosis of the femoro-patellar joint and in patients with rheumatoid arthritis,
      however, the patella replacement is considered to be the therapy of choice at our
      department.

PMID- 9563188
TI  - [3-dimensional surface measurement of spinal deformities with video
      rasterstereography].
AB  - QUESTION: Video rasterstereography is a method for back surface measurement
      comprising automatic back surface reconstruction and shape analysis. Aim of this
      prospective study was to determine the accuracy of this method in comparison to
      the conventional frontal and lateral standing radiographs. METHOD: 95 patients
      with idiopathic scoliosis or scoliotic postural abnormalities and 18 patients
      with thoracic hyperkyphosis and Scheuermann's disease were investigated. The Cobb
      angles, the sagittal profile and apical vertebral rotation as well as pelvic
      obliquity and trunk decompensation were measured. The analysis was carried out by
      two independent observers. RESULTS: The root mean square (r.m.s.) deviation of
      the Cobb angle in the cases of idiopathic scoliosis ranged between 7 degrees and
      8 degrees. In video rasterstereography there were no false negative results and
      two false positive results concerning differentiation between structural
      scoliosis and scoliotic postural abnormality. The r.m.s. deviation of apical
      vertebral rotation averaged 7.9 degrees and for pelvic obliquity respectively
      trunk imbalance 0.65 cm respectively 1.07 cm. The thoracic hyperkyphosis in
      Scheuermann's disease showed a r.m.s. deviation of 5.6 degrees. CONCLUSIONS:
      Video rasterstereography is a reliable method in the three-dimensional evaluation
      of spinal deformities and constitutes a valuable additional tool to the clinical
      examination and can reduce the number of radiographs.

PMID- 9563190
TI  - [Is use of the Knee Society Roentgenographic Evaluation and Scoring System for
      radiologic control of knee prostheses reliable?].
AB  - PURPOSE: To follow the radiographic parameters of prosthetic loosening of the
      Knee Society Roentgenographic Evaluation and Scoring System (KSRESS) and to test
      their clinical relevance. METHODS: This prospective study documents the use of
      the KSRESS and clinical rating system in 333 primary posterior cruciate retaining
      PFC total knee arthroplasties preoperatively, at 3 month and at yearly intervals
      postoperatively. The average follow-up period was 3.2 years (range 2-5.5 y).
      RESULTS: The average component position and alignment angles remained unchanged
      at biomechanically correct angles during the follow-up period. Radiolucent lines
      were observed regularly at the edges of the tibial and femoral components. The
      average total radiolucent lines score decreased for the tibial component.
      Patellar and femoral lucencies remained unchanged. The total radiolucent lines
      scores did not correlate with postoperative pain, body-mass-index, alignment,
      stability, knee and function score. Four revisions, one with relevant radiolucent
      lines, had to be performed. CONCLUSIONS: The KSRESS is a useful tool.
      Standardisation of roentgenograms is mandatory. The PFC arthroplasty, the
      operative technique and the instruments ensure a biomechanically correct
      implantation.

PMID- 9563191
TI  - [Diagnosis and long-term outcome after surgical therapy of tarsal tunnel
      syndrome].
AB  - In differential diagnosis of foot pain the tarsal tunnel syndrome has to be
      considered. Only few publications concerning clinical signs, diagnostic means,
      especially electrophysiological methods and postoperative long term results can
      be found in literature. In this study 21 of 32 patients who had a decompression
      operation of the posterior tibial nerve between 1972 and 1995 were reexamined at
      an average follow-up time of 12 years. Electrodiagnostic evaluation and clinical
      results by time of follow-up were compared to preoperative findings. Using the
      criteria described by Kaplan 10 postoperative results were rated as very good, 6
      as good and 5 as poor. Sensible neurography has proven the most sensitive
      electrodiagnostic method. In the majority of cases the tarsal tunnel syndrome is
      still a clinical diagnosis.

PMID- 9563192
TI  - [Long-term results of single stem silastic implants in the metatarsophalangeal
      joint].
AB  - AIM OF THE STUDY: Long-term results of single stemmed silicone prostheses.
      METHOD: 61 feet were reviewed after a mean follow-up time of 13 years. RESULTS:
      18 implants (29.5%) have been removed, 7 of them in the first year after
      operation. The often impressive radiologic changes showed no correlation to the
      subjective results but a correlation to time. 1/3 of the patients were not
      satisfied with the outcome. An average of 75% of the prosthesis was destroyed
      after 10 years, 93.5% were loosened. CONCLUSION: By reason of the high rate of
      failure of the implant, we have abandoned this procedure.

PMID- 9563193
TI  - [Funicular myelosis--an unusual case of unilateral destruction of the tarsus].
AB  - The presentation includes an unusual destruction of the tarsus of a 64 year old
      patient with subacute combined degeneration of the spinal cord caused by
      chronical vitamin-B12-deficiency. This case report will be shown a systemical
      disease as a possible cause of localized bone-destruction in
      differentialdiagnosis.

PMID- 9563194
TI  - Risk assessment in Lyme borreliosis.

PMID- 9563195
TI  - Identification of Borrelia burgdorferi sensu lato species in Europe.
AB  - Characterisation at the species level of 142 Borrelia isolates obtained from
      ticks, humans and rodents in Western Europe was carried out and their
      geographical distribution was described. Borrelia garinii was the predominant
      species representing 44% of the isolates and B. afzelii and B. burgdorferi sensu
      stricto constituted 27% and 19% of isolates respectively. B. valaisiana,
      (formerly group VS116) constituted 10.5% of isolates. Some differences in the
      Borrelia species distribution were observed from one country to another, possibly
      linked to different sources of samples. In the human samples, which were mostly
      collected in Austria, B. afzelii was preferentially isolated from skin and B.
      garinii from CSF. B. afzelii was consistently isolated from rodents captured in
      Switzerland, but one isolate of B. garinii was obtained from a rodent in Austria.
      B. garinii was by far the most abundant species isolated from Ixodes ricinus
      ticks in all studied countries. B. valaisiana was isolated from I. ricinus ticks
      collected from vegetation and from I. ricinus engorged on birds.

PMID- 9563196
TI  - Detection of Borrelia burgdorferi sensu lato in ticks: immunofluorescence assay
      versus polymerase chain reaction.
AB  - Immunofluorescence (IFA) and polymerase chain reaction (PCR) were examined as
      methods for detecting Borrelia burgdorferi sensu lato spirochaetes in unfed
      Ixodes ricinus nymphs. Although similar results were produced in some cases, a
      great deal of variation occurred. Furthermore, in both the highly controlled
      initial laboratory study, involving 252 shared samples, and the study on field
      collected ticks (n = 460), the IFA tended to detect more infected ticks than the
      PCR. The basis for these findings are as yet undetermined. The development of a
      quality assurance scheme is recommended so that laboratories can validate their
      methods and a preliminary feasibility study suggested that such a scheme is
      practical.

PMID- 9563197
TI  - Epidemiology of European Lyme borreliosis.
AB  - Lyme borreliosis occurs throughout Europe and is particularly prevalent in the
      east. In a small proportion of untreated cases serious sequelae may occur, but
      Lyme borreliosis alone does not cause death. Clinical and serological diagnosis
      can still be problematic and the various genomospecies may cause different
      disease manifestations as well as differing immunological responses. However,
      considerable progress has been made in standardising case definitions and
      serological testing and interpretation. Few countries have official reporting
      systems for Lyme borreliosis and most figures on incidence are extrapolated from
      serodiagnosis data and seroprevalence studies. Geographical variations in
      incidence seem to correlate with the prevalence of infected ticks, which are
      mainly associated with varied deciduous forest. The complex ecology of Lyme
      borreliosis makes it difficult to implement preventive measures, so improving
      public knowledge of risk factors and methods for personal protection remain the
      best option at present.

PMID- 9563199
TI  - European Lyme borreliosis clinical spectrum.
AB  - At a series of meetings, involving 27 clinicians from 11 countries, case
      definitions for the diagnosis of Lyme borreliosis in Europe were agreed and are
      presented here, with appropriate serological criteria, as a diagnostic guide. In
      a separate study questionnaires directed to clinicians were used to collect
      information on clinical aspects and risk factors of Lyme borreliosis. Data on the
      number of Lyme borreliosis patients seen by physicians indicated a low prevalence
      of the disease in western Europe and a relatively high prevalence in eastern
      Europe. The most commonly encountered symptom was erythema migrans, followed by
      neurological manifestations. Cardiac problems were rare. Tick bite was strongly
      associated with Lyme borreliosis, but the only other significantly associated
      risk factor was the pastime of gardening.

PMID- 9563198
TI  - European interlaboratory comparison of Lyme borreliosis serology.
AB  - Serological testing for Lyme borreliosis was compared in 5 European reference
      laboratories with a total of 79 sera in order to determine variations in
      laboratory performance. A considerable range of methods were used and several
      laboratories employed 2 or 3 genomospecies of Borrelia burgdorferi sensu lato. No
      laboratory relied routinely on a single test and each weighted the significance
      of the findings of the various tests differently. A difference in strategy
      between laboratories in high and low prevalence areas was apparent in that
      laboratories in low prevalence areas emphasised specificity more than sensitivity
      and therefore produced fewer false positives, but also missed some cases. Overall
      agreement between the laboratories was poor and it was concluded that there is a
      need for a quality assurance scheme within Europe.

PMID- 9563201
TI  - The European Union Concerted Action World Wide Web site for Lyme borreliosis.
AB  - This web site (URL http://www.dis.strath.ac.uk/vie/LymeEU/) provides information
      on Lyme borreliosis for physicians, scientists, health care workers,
      veterinarians and students. It consists of a review of the spirochaetes, vectors,
      reservoir hosts, diagnosis, treatment, epidemiology and prevention of the
      disease, as well as an account of the activities of EUCALB.

PMID- 9563200
TI  - Lyme borreliosis awareness.
AB  - A Lyme borreliosis information leaflet has been produced to promote awareness
      amongst the general public. It was designed to provide a framework for similar
      material throughout Europe and complements a questionnaire produced to measure
      awareness of Lyme borreliosis. This questionnaire can be used to determine the
      impact of educational campaigns using material such as the leaflet. Feasibility
      studies showed that the questionnaire successfully highlighted predictable
      differences between sample groups and also that the leaflet performed well in
      increasing knowledge in low-awareness groups.

PMID- 9563202
TI  - The use of stable isotope labeling and liquid chromatography-tandem mass
      spectrometry techniques to simultaneously determine the oral and ophthalmic
      bioavailability of timolol in dogs.
AB  - Assays have been established for the quantitation of timolol and its 13C3- and
      2H9-stable-isotope-labeled analogs in plasma and urine using liquid
      chromatography with atmospheric-pressure chemical-ionization tandem mass
      spectrometry. For the analysis of urine, underivatized timolol and its labeled
      analogs are monitored while timolol in plasma is assayed down to concentrations
      of 0.2 ng/mL after derivatization with phosgene. The great power of this
      technique is illustrated by simultaneously assaying three different species of
      timolol in plasma and urine obtained from dogs receiving simultaneous ophthalmic,
      oral, and intravenous doses of unlabeled and [2H9]- and [13C3]-labeled timolol.
      Thus, the ophthalmic and oral bioavailabilities of timolol are measured in a
      single experiment rather than as a three-phase crossover experiment. This
      approach yields accurate and precise analytical data, obviates intrasubject
      variability, and saves both analytical and animal resources.

PMID- 9563204
TI  - Development and validation of an ion-exclusion chromatographic method for the
      quantitation of organic acids in complex pharmaceutical products.
AB  - Effective quantitation of organic acids (acetic, malic, and lactic acids) present
      in total parenteral nutrition (TPN) pharmaceutical products for final product
      release purposes requires accuracy, precision, and specificity but less than
      optimal sensitivity. A chromatographic method relying on ion-exclusion separation
      and low-wavelength ultraviolet detection has been developed and validated to
      quantitate these organic acids in matrices containing 10-fold or greater excesses
      of other constituents (sugars, amino acids, and other inorganic salts) with no
      sample preparation other than dilution. Mobile phases at slightly different pH
      values effectively eliminates matrix-related interferences that were observed
      during the analysis of several products. The validation procedure used is
      discussed in terms of its strategy and results. Ultimately, the assay is found to
      be appropriate for the release testing of several compositionally diverse TPN
      products.

PMID- 9563203
TI  - Highly sensitive and specific assay of plasma melatonin using high-performance
      liquid chromatography with fluorescence detection preceded by solid-phase
      extraction.
AB  - This paper describes a new, highly sensitive, rapid method for the determination
      of low levels of endogenous melatonin, the pineal and retinal hormone, in fish
      plasma samples. The combination of solid-phase extraction and high-performance
      liquid chromatography with fluorescence detection significantly improves the
      separation and increases the sensitivity of the assay. The proposed method may be
      a useful alternative to previously reported procedures. The assay should be
      applicable to plasma and tissue samples from other animals, including humans,
      with only minor modifications.

PMID- 9563205
TI  - Measles vaccine saves lives.

PMID- 9563206
TI  - Rising incidence of parvovirus B19 infection.

PMID- 9563207
TI  - The long-term tolerability and efficacy of oral zolmitriptan (Zomig, 311C90) in
      the acute treatment of migraine. An international study. The International 311C90
      Long-term Study Group.
AB  - This international open-label study evaluated the tolerability and efficacy of
      zolmitriptan (Zomig, 311C90), a selective 5-HT1B/1D receptor agonist, in the long
      term treatment of multiple migraine attacks. Patients who had previously
      participated in placebo-controlled zolmitriptan studies were recruited. A total
      of 2058 patients treated 31,579 migraine attacks (average 15 per patient), for up
      to 1 year. Twenty-six percent of attacks treated with a single zolmitriptan 5-mg
      dose were associated with at least one adverse event (24% treated with two
      doses). The most frequent adverse events included asthenia (14% of patients),
      nausea (12%), somnolence (10%), dizziness (11%), and paresthesia (11%). The rank
      order of the most common adverse events was not influenced by sex, age, or number
      of zolmitriptan doses taken and was similar between attacks 1 and 45. The
      majority of adverse events (59%) occurred within 2 hours of dosing, were of
      either mild (59%) or moderate (35%) intensity, of 4 hours' duration or less
      (67%), and required no further action (94%). Following an initial 5-mg dose of
      zolmitriptan, the 2-hour headache response rate (reduction in headache pain from
      moderate or severe before treatment to mild or no pain at 2 hours posttreatment)
      was 81% in patients treating moderate and severe attacks (19,639 of 24,161).
      Patients were pain-free at 2 hours in 55% of all attacks (16,510 of 29,808). The
      efficacy of zolmitriptan was not influenced by age, sex, weight, use of
      prophylactic antimigraine medication, or association of attacks with
      menstruation. Analysis of the overall population and a subgroup who treated 30 or
      more migraine attacks showed that zolmitriptan was consistently effective across
      attacks. Overall, 67% of patients who treated five or more attacks reported
      zolmitriptan to be effective in 80% to 100% of attacks. Zolmitriptan produced
      meaningful migraine relief and improvement in normal activity impairment in 73%
      and 78% of moderate and severe attacks, respectively. Patients treated recurrence
      of moderate or severe headache with a second zolmitriptan dose in 32% of attacks
      which responded to the first dose within 2 hours. Where required, a second
      zolmitriptan 5-mg dose for treatment of recurrence produced a headache response
      rate of 90% at 2 hours postdose. Thus, zolmitriptan 5 mg (plus an optional second
      5-mg dose for treatment of recurrence) is well tolerated and effective in the
      acute treatment of multiple migraine attacks over periods up to 1 year.

PMID- 9563208
TI  - Efficacy and safety of sumatriptan tablets (25 mg, 50 mg, and 100 mg) in the
      acute treatment of migraine: defining the optimum doses of oral sumatriptan.
AB  - That sumatriptan tablets are effective and well tolerated in the acute treatment
      of migraine has been established, but the relationship between dose and efficacy
      has not been adequately defined to date in clinical trials. This multinational
      double-blind trial (N = 1003) in which patients treated up to three migraine
      attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second
      independently randomized dose for headache recurrence, evaluated the efficacy and
      tolerability of three doses of sumatriptan. The results demonstrate that all
      doses of sumatriptan were superior (P < 0.05) to placebo in reducing moderate or
      severe predose headache to mild or no headache 4 hours postdose for each of the
      three treated attacks; sumatriptan 50 mg and 100 mg were each superior (P < 0.05)
      to sumatriptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all
      doses) was similarly effective at relieving nausea and photophobia or phonophobia
      or both and at reducing clinical disability. Headache recurrence was experienced
      by similar proportions of patients across treatment groups (35% to 48% after
      placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours
      after the second dose of study medication occurred in greater percentages of
      patients using any dose of sumatriptan compared with patients using placebo to
      treat recurrence. The incidence of adverse events with 25-mg and 50-mg
      sumatriptan tablets was similar to the incidence with placebo and lower than the
      incidence with 100-mg sumatriptan tablets. These data provide the first
      demonstration from a large well-controlled clinical trial that both the 50- and
      100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is
      associated with a lower incidence of adverse events than the 100-mg dose.

PMID- 9563209
TI  - Presentation of chronic daily headache: a clinical study.
AB  - We studied the presentation of chronic daily headache in 258 patients from a
      private headache practice, 50 men and 208 women. Chronic daily headache was
      defined as headaches, occurring at least 5 days per week for at least 1 year.
      Seventy-seven percent of the patients experienced the onset of headache before
      the age of 30. The daily headaches were present on awakening in the morning or
      came about in the course of the morning in 79% of the patients. In 53%, they were
      worst in the afternoon or evening. The headaches awoke the patients at night at
      least once per week in 36%. At least twice per week, they were associated with
      nausea in 35% of the patients and with vomiting in 9%. Common aggravating factors
      included light, physical activity, bending over, noise, stress or tension, and
      menstruation. Ninety-four percent of the patients experienced severe headaches in
      addition to the daily headaches. In 63%, the severe headaches occurred 10 days
      per month or less. The daily caffeine intake of the patients averaged 170 mg, and
      the daily analgesic intake, 1860 mg of aspirin equivalents.

PMID- 9563212
TI  - Initial exploration of pulsing electromagnetic fields for treatment of migraine.
AB  - Two studies were conducted during which 23 patients with chronic migraine were
      exposed to pulsing electromagnetic fields over the inner thigh. In an open study,
      11 subjects kept a 2-week headache log before and after 2 to 3 weeks of exposure
      to pulsing electromagnetic fields for 1 hour per day, 5 days per week. The number
      of headaches per week decreased from 4.03 during the baseline period to 0.43
      during the initial 2-week follow-up period and to 0.14 during the extended follow
      up which averaged 8.1 months. In a double-blind study, 9 subjects kept a 3-week
      log of headache activity and were randomly assigned to receive 2 weeks of real or
      placebo pulsing electromagnetic field exposures as described above. They were
      subsequently switched to 2 weeks of the other mode, after which they kept a final
      3-week log. Three additional subjects in the blind study inadvertently received
      half-power pulsing electromagnetic field exposures. The 6 subjects exposed to the
      actual device first showed a change in headache activity from 3.32 per week to
      0.58 per week. The 3 subjects exposed to only half the dose showed no change in
      headache activity. Large controlled studies should be performed to determine
      whether this intervention is actually effective.

PMID- 9563210
TI  - Chronic paroxysmal hemicrania and hemicrania continua: lack of efficacy of
      sumatriptan.
AB  - Attacks of chronic paroxysmal hemicrania are prevented by the continuous
      administration of indomethacin. Sumatriptan, an agonist of 5-HT1-like receptors,
      has proven effective in the treatment of cluster headache attacks. There are
      clear clinical similarities between chronic paroxysmal hemicrania and cluster
      headache. A natural consequence of these considerations would be to establish
      whether chronic paroxysmal hemicrania also responds similarly to sumatriptan.
      Since hemicrania continua is another unilateral headache responsive to
      indomethacin, it would be meaningful to also include hemicrania continua in such
      a study. Sumatriptan, 6 mg subcutaneous, was tried in an open fashion in 7
      patients (6 women and 1 man) with chronic paroxysmal hemicrania and 7 patients (5
      women and 2 men) with hemicrania continua. In chronic paroxysmal hemicrania, the
      mean interval between the last three attacks prior to sumatriptan treatment (40
      +/- 23 minutes) was not statistically different from the mean interval between
      the three attacks subsequent to sumatriptan treatment of an attack (32 +/- 20
      minutes). In none of the patients did the mean duration of the "test attack"
      decrease as compared to the attacks antedating the test attack (25 +/- 11 minutes
      and 19 +/- 9 minutes, respectively) (P = 0.027, Wilcoxon). In 2 patients with
      chronic paroxysmal hemicrania, placebo (saline) administration did not lead to
      any change in the interval between attacks. There was a mild, but statistically
      significant reduction in visual analog scale values for headache intensity in
      hemicrania continua (P = 0.04, Wilcoxon). There was no clear, i.e., clinically
      meaningful, reduction in visual analog scale values in any particular patient
      with hemicrania continua. Taken together, these results seem to show that
      sumatriptan is of no benefit in chronic paroxysmal hemicrania, but may have a
      partial efficacy in hemicrania continua. However, the latter effect is clinically
      unimportant. This minor difference in regard to the clinical effect may,
      nevertheless, be of some interest pathogenetically, indicating minor differences
      between the two headaches. The lack of sumatriptan effect in chronic paroxysmal
      hemicrania clearly and markedly strengthens the nonalignment concept in regard to
      chronic paroxysmal hemicrania and cluster headache.

PMID- 9563211
TI  - Tolfenamic acid rapid release versus sumatriptan in the acute treatment of
      migraine: comparable effect in a double-blind, randomized, controlled, parallel
      group study.
AB  - The efficacy and safety of tolfenamic acid and oral sumatriptan in the acute
      treatment of migraine was studied at five neurological centers in Finland. One
      hundred forty-one patients experiencing 289 migraine attacks, fulfilling the
      diagnostic criteria for migraine with or without aura as defined by the
      International Headache Society, were randomized. For first attacks, 77% of
      patients receiving tolfenamic acid experienced a reduction of the initial severe
      or moderate headache to mild or no headache after 2 hours, as compared to 79% in
      the sumatriptan group and 29% in the placebo group. No significant difference was
      found between active treatments (P = 0.85, 95% CI [-22%, 18%]), however, both
      active treatments were significantly better than placebo; P = 0.001, 95% CI (26%,
      69%) for tolfenamic acid and P = 0.001, 95% CI (28%, 71%) for sumatriptan. For
      second attacks, results were similar with 70% of patients receiving tolfenamic
      acid experiencing relief, as compared to 64% in the sumatriptan group and 39% in
      the placebo group. No significant differences were observed in accompanying
      symptoms. Both drugs were well tolerated with the frequency of adverse events;
      30% for tolfenamic acid and 41% for sumatriptan, a nonsignificant difference. In
      this study, tolfenamic acid and oral sumatriptan are comparably effective in the
      acute treatment of migraine. When comparably effective, factors like individual
      effect, tolerance, and cost of treatment should be considered when prescribing
      migraine medication.

PMID- 9563213
TI  - Relationships between arousal-related moods and episodic tension-type headache: a
      biopsychological study.
AB  - An exploratory study was conducted examining arousal-related moods and episodic
      tension-type headache. Twelve subjects meeting International Headache Society
      criteria for episodic tension-type headache and 12 headache-free controls
      recorded headache activity and mood eight times daily for 14 consecutive days.
      Moods were measured using the Activation-Deactivation Adjective Check List, a
      self-report list that subjectively represents general arousal along two
      dimensions of Tension and Energy. Headache subjects had higher Tension levels
      than controls even in the absence of pain, and greater variation in this
      dimension as well. Within the headache group, Tension during pain-free periods
      was significantly lower than when experiencing headache, and was correlated with
      headache activity. The results were taken to support Thayer's (1989)
      biopsychological model of mood and arousal, and are discussed in terms of the
      model's heuristic value for general arousal and headache research.

PMID- 9563214
TI  - Social environment and headache in 8- to 9-year-old children: a follow-up study.
AB  - We studied the occurrence of migraine and nonmigrainous headache and the factors
      associated with headache in a group of 3580 children. These children belong to a
      1-year age cohort which has been followed since birth. When the children were 8
      to 9 years old, data on their headaches were gathered through a postal
      questionnaire. Ninety-five of the children (2.7%) had migraine and 977 (27.3%)
      reported non-migrainous headache at the age of 8 to 9 years. Thirty-four percent
      of the children with migraine had already had headache at the age of 5 years.
      Children with migraine and children with nonmigrainous headache both reported
      more often being bullied in school, stress in school, and problems in getting
      along with other children than children without headache. The association of
      stress in school with headache was strongest in girls with migraine, even though
      they reported the least difficulties in school subjects. As many as one third of
      the boys with migraine reported that they had problems with peer relationships.

PMID- 9563215
TI  - Time required for improvement of an analgesic rebound headache.
AB  - There is typically delayed improvement in analgesic rebound headache after the
      offending agents have been discontinued. This case history documents that, at
      times, it might be necessary to omit medications for 6 months until the almost
      daily headaches cease.

PMID- 9563216
TI  - Predictors of outcome in fulminant hepatic failure in children.
AB  - OBJECTIVE: To identify the predictors of outcome in fulminant hepatic failure
      (FHF) in children. STUDY DESIGN: Prospective cohort study. METHODS: 41 children
      with FHF were studied. Patient characteristics and findings on examination at the
      time of hospitalization were noted. Serum biochemistry and screening for
      hepatotropic viruses (A, B and C) were done in each patient. Patients were
      treated using a predefined protocol and followed up till death or discharge.
      Univariate and multivariate analysis was done to find the predictors of outcome.
      RESULTS: Hepatitis B was the commonest cause of FHF (11 children; 26.9%). Markers
      for hepatitis A and C viruses were present in one and two patients, respectively.
      Serology was negative in 27 children (65.9%), of whom two had history of
      ingestion of hepatotoxins (antitubercular drugs). The overall mortality was 61%.
      Irrespective of etiology, the following factors were associated with poor outcome
      on univariate analysis: presence of gastrointestinal (GI) hemorrhage, serum
      bilirubin more than 10 mg/dL, age 6 years or less, coma of grade 3 or more,
      presence of infection, prolongation of prothrombin time > 8 s over control,
      prothrombin concentration < 50%, hypoglycemia (blood glucose < 45 mg/dL),
      hyponatremia (serum sodium < 125 mEq/L) and hyperkalemia (serum potassium > 5.5
      mEq/L). On multiple logistic regression analysis, presence of GI hemorrhage (p =
      0.005), degree of coma (p = 0.02) and serum bilirubin level (p = 0.025) were
      identified as independent predictors of mortality.

PMID- 9563217
TI  - Complicated sigmoid diverticulosis.
AB  - BACKGROUND: To evaluate the outcome of patients treated for complications of
      sigmoid diverticular disease. METHODS: Fifteen patients (11 women; aged 54-80
      years) were treated over a 6-year period in a community hospital. Five patients
      presented with perforation and peritonitis, 3 with colovesical fistula, 2 with
      colovaginal fistula, 2 with recurrent phlegmon and 3 with bleeding. Six patients
      (5 with perforation, 1 colovesical fistula with hematuria) underwent emergency
      surgery. Six patients (2 with colovesical fistula, 2 colovaginal fistula and 2
      recurrent phlegmon) underwent planned sigmoid resection. All 3 patients with
      bleeding were treated conservatively. RESULTS: One patient with a colovesical
      fistula and severe hematuria died 72 hours later with septicemia. All 5 patients
      with peritonitis survived; two had an eventful post-operative period and were in
      hospital for nearly 3 months. All 5 developed wound sepsis. Six patients who had
      a planned procedure had uneventful recovery. The 3 patients who presented with
      bleeding recovered. CONCLUSION: Complicated diverticular disease carries a high
      morbidity and mortality especially when operated on as an emergency. Interval
      sigmoid resection should be offered to patients who have recovered from an acute
      complication.

PMID- 9563220
TI  - Randomized double-blind trial of metronidazole versus secnidazole in amebic liver
      abscess.
AB  - OBJECTIVE: To compare the efficacy of secnidazole with metronidazole in the
      treatment of amebic liver abscess. METHODS: Thirty two patients with
      uncomplicated liver abscesses were studied in a randomized, double-blind trial.
      Fifteen received metronidazole (400 mg t.i.d. for 7 days) and 17 secnidazole (500
      mg t.i.d. for 5 days). All abscesses were aspirated on day 1 and laboratory tests
      and ultrasonographic examination were done on days 1 and 10. RESULTS: One patient
      in the metronidazole group developed intraperitoneal rupture. The other 31
      patients had 40 abscesses (19 in metronidazole group, 21 in secnidazole group).
      Complete resolution of signs occurred by day 10 in 10 patients on metronidazole
      and 12 on secnidazole, and in all others by day 28. On day 10 ultrasonography in
      the metronidazole group showed complete disappearance of abscess in one patient,
      decrease in 8 and increase in 5 (versus 2, 12 and 3, respectively in the
      secnidazole group). After 6 months, four asymptomatic patients (two from each
      group) had small abscess cavities on ultrasonography; there were no recurrences.
      CONCLUSIONS: Secnidazole is as effective in the treatment of amebic liver abscess
      as metronidazole; it is equally well tolerated.

PMID- 9563221
TI  - Manometric mapping of normal esophagus and definition of the transition zone.
AB  - BACKGROUND: The normal esophagus has not been manometrically mapped. The
      transition zone between esophageal smooth and skeletal muscles has also not been
      defined manometrically. AIMS: To manometrically map the normal esophagus and to
      define the transition zone. METHODS: Thirty normal adults [23 men; mean age 34.8
      (10.4) years] underwent manometry using a water-perfused system. The lower
      esophageal sphincter (LES) was studied by station pull-through, and esophageal
      body musculature was evaluated at 1-cm intervals with five wet swallows at each
      level. The transition zone was identified as an area where the wave-forms did not
      resemble typical skeletal or smooth muscle wave-forms. RESULTS: The basal mid
      expiratory LES pressure was 18.7 (7.2) mmHg, and its length was 3.6 (1.2) cm.
      Based on our findings, we defined the transition zone as an area where either the
      amplitude of contraction was < 40 mmHg or, if the amplitude was 40-50 mmHg, the
      rate of change of pressure from baseline to peak of the wave was < 50 mmHg/s. The
      lengths of the skeletal, transition and smooth muscle zones were 2.8 (1.2), 4.0
      (1.7) and 12.5 (2.7) cm, respectively. The amplitude and dp/dt of contraction and
      transmission velocity were lowest in the transition zone (p < 0.05). CONCLUSIONS:
      We have manometrically mapped the normal esophageal muscle zones; the parameters
      obtained may be used as reference values. The manometric criteria for the
      transition zone have also been defined.

PMID- 9563218
TI  - Natural history of severe duodenal ulcer disease.
AB  - BACKGROUND: A subset of patients with chronic duodenal ulcer has severe ulcer
      diathesis in the form of frequent relapses and complications like perforation and
      hemorrhage. We observed the effect of drug treatment on the natural history of
      this subset. METHODS: Of 526 patients diagnosed to have chronic duodenal ulcer by
      endoscopy, 23 patients with severe diathesis were available for long follow-up
      (mean period 36 months). Each patient was assessed clinically and endoscopically
      every 2 months for at least 12 months and then every 3 months or when
      symptomatic. Helicobacter pylori status was assessed during endoscopy. The effect
      of antisecretory drugs and anti-H. pylori therapy on natural history was
      determined. RESULTS: Thirteen of 23 patients (56%) had refractory ulcers; six
      responded to double dose of H2-receptor antagonists (H2RA) for 8 weeks and six to
      omeprazole 40 mg daily for 4-8 weeks. Of 20 patients (87%) who were H. pylori
      positive, 15 completed triple-drug therapy; of these, 10 patients eradicated H.
      pylori. These 10 patients were followed up for 24 months; there were no ulcer
      relapses within the first 12 months but 8 of them relapsed between 12 and 24
      months (total number of relapses 8). Reinfection with H. pylori occurred in 3
      patients. In the other 10 patients who remained H. pylori-positive, there were 19
      episodes of ulcer relapse in 7 patients over 24 months, in spite of maintenance
      therapy with H2RA (p < 0.05). CONCLUSIONS: Refractoriness in patients with severe
      ulcer disease is usually episodic and amenable to larger doses of omeprazole or
      H2RA. Anti-H. pylori therapy improves the natural history but its effect in
      preventing ulcer relapse is short lasting (less than 12 months). Recurrence of
      infection is a problem in our population.

PMID- 9563219
TI  - Assessment of effects of propranolol on portal hemodynamics in cirrhosis by
      duplex ultrasonography.
AB  - OBJECTIVE: To study the effect of propranolol on portal hemodynamics in
      cirrhotics using duplex ultrasonography. METHODS: Portal venous flow was measured
      by duplex ultrasonography in 12 healthy volunteers and ten men with cirrhosis.
      The cirrhotics were evaluated prior to and after ingestion of propranolol (60 mg
      twice daily for seven days) or placebo in a randomized cross-over fashion.
      Variations in heart rate, blood pressure, portal vein diameter, and portal venous
      flow and velocity were evaluated. RESULTS: The mean (SD) portal venous flow in
      the volunteers was 746 (280) mL/min, portal flow velocity was 18.5 (3.6) cm/s and
      portal vein diameter was 9.2 (1.4) mm. In cirrhotics, propranolol decreased
      portal blood flow from 586 (220) to 413 (120) mL/min (p < 0.03), the overall
      reduction being 29.5%. This effect was due to decrease in portal flow velocity,
      from 12.5 (3.3) to 9.7 (2.3) cm/s (p < 0.03) without significant change in portal
      vein diameter. No changes were observed with placebo. CONCLUSIONS: Propranolol
      decreases portal flow velocity and thus portal venous flow in cirrhotics.

PMID- 9563222
TI  - Differentiation of pathogenic and non-pathogenic Entamoeba: has the question been
      answered?
AB  - Pathogenic and non-pathogenic Entamoeba have been separated into two distinct
      species. Recently, the non-pathogenic E. dispar has been cultivated axenically.
      However, the genetic variability among different clones from the same strain,
      experimental production of hybrid clones which may differ from their parents, and
      the possibility of invasiveness of E. dispar, are some phenomena which may
      indicate that the last word on distinctiveness of the species has not yet been
      said.

PMID- 9563223
TI  - Bleeding duodenal varices: successful treatment with proximal lienorenal shunt.

PMID- 9563224
TI  - Membranous glomerulonephritis in association with ulcerative colitis.
AB  - Glomerulonephritis is a rare association of ulcerative colitis. We report a
      patient with ulcerative colitis who developed proteinuria due to membranous
      glomerulonephritis which responded to colectomy.

PMID- 9563225
TI  - Fetus in fetu.
AB  - Fetus in fetu occurs due to aberration of monozygotic twinning. A 16-year-old boy
      presented with abdominal pain and mass. Laparotomy revealed an anencephalic fetus
      within an encapsulated retroperitoneal mass. Pathologic examination confirmed rib
      formation with a primitive vertebral column with bone marrow. There was no other
      organogenesis.

PMID- 9563226
TI  - Inflammatory myoglandular polyp of rectum.

PMID- 9563227
TI  - Spontaneous rupture of mid-esophagus.

PMID- 9563228
TI  - Periampullary carcinoma with bilateral ovarian cystadenoma in pregnancy.
AB  - We report a 30-year-old woman with periampullary cancer and a large left ovarian
      cystadenoma presenting during pregnancy with features of duodenal obstruction.
      She had a right benign ovarian tumor removed a year back. She delivered an
      intrauterine-growth-retarded live baby. Laparotomy in the postpartum period
      revealed an unresectable periampullary growth with hepatic metastasis and a left
      ovarian cystadenoma. The ovarian tumor was removed and a palliative
      gastrojejunostomy performed.

PMID- 9563229
TI  - Marked perisplenitis in gastric carcinoma.
AB  - We report a patient with gastric carcinoma with marked perisplentis, on gross
      appearance resembling secondary deposit. On sectioning, the spleen showed a
      solitary metastasis in the red pulp.

PMID- 9563230
TI  - Wandering spleen causing splenic flexure volvulus and obstruction.
AB  - A 48-year-old woman presented with symptoms of distal bowel obstruction. On
      examination she had abdominal distension and a lump in the left lumbar and iliac
      regions. X-ray revealed distension of the colon with dilated small bowel.
      Exploration revealed an enlarged ptotic spleen whose pedicle caused obstruction
      of the colon. There was concomitant partial volvulus of the splenic flexure
      around the splenic pedicle. The splenic vein was thrombosed. Splenectomy was
      performed.

PMID- 9563231
TI  - Gall bladder carcinoma presenting as liver abscess.
AB  - Perforation of malignant gall bladder resulting in liver abscess and presenting
      as pyrexia of unknown origin is rare. We report a patient who was diagnosed at
      surgery, which was undertaken with a diagnosis of liver abscess on CT scan.

PMID- 9563232
TI  - Flush endoscopic variceal injectors with acetone after glue injection.

PMID- 9563233
TI  - Hepatitis B acquired from a barber's shop.

PMID- 9563234
TI  - Polypectomy: no right way to do wrong things.

PMID- 9563235
TI  - Introduction to special issue on group psychotherapy for the medically ill.

PMID- 9563237
TI  - Group therapy and organ transplantation.
AB  - Group therapy for organ transplantation patients is in its infancy but has a
      promising future. Overextended transplantation service providers are interested
      in its potential for cost-efficient and effective forms of psychosocial
      intervention. This article summarizes the biomedical and psychosocial aspects of
      solid organ transplantation, one institution's group therapy program, common
      group themes, and specific demands on the group therapist working with this
      population.

PMID- 9563236
TI  - Group psychotherapy for persons with HIV and AIDS-related illnesses.
AB  - Although some individuals are able to cope well with the challenges posed by HIV
      and AIDS, others experience psychological difficulties. This article reviews
      factors that facilitate or hinder successful coping with HIV including
      preexisting psychological functioning, medical health status, quality and
      adequacy of social support, stress-and-coping style, and perceived expected
      benefits of treatment. The article reviews studies evaluating the effects of
      group psychotherapy intervention for persons living with HIV. The article then
      describes clinical issues encountered in therapy groups for persons with HIV.
      These clinical issues include the presence of coexisting problems unrelated to
      HIV/AIDS, disclosure of HIV-positive serostatus to others, making changes in
      transmission-risk-behavior practices, AIDS-related bereavement and caregiving
      stress, establishing social supports, adhering to medical care regimens, and
      developing a positive self-identity as a person living with HIV. Practical
      considerations of group therapy for HIV-positive clients are also described.

PMID- 9563238
TI  - Group psychotherapy for patients with coronary heart disease.
AB  - Group therapy with cardiac patients is a relatively new specialty. The field is
      supported by a substantial epidemiological and experimental literature
      demonstrating links between heart and mind. There are several clinical trials
      that have demonstrated less morbidity, improved quality of life, and, to some
      extent, lower mortality for patients who have received psychosocial intervention,
      generally group therapy, compared to control patients. Different theoretical
      orientations and a small number of clinical techniques have been developed to
      help cardiac patients make an adjustment to heart-healthy living. This article
      provides a brief review of the literature in cardiac psychology, suggestions for
      developing a psychotherapy practice specialty with cardiac patients, techniques
      for treating these patients, and conclusions by a psychologist-cardiologist team
      that has been active in this area for more than a decade.

PMID- 9563239
TI  - Cognitive-behavioral group therapy for patients with irritable bowel syndrome.
AB  - This article is divided into two parts, the first of which focuses on a general
      overview of irritable bowel syndrome (IBS) and provides a rationale for the use
      of cognitive-behavioral therapy (CBT) for IBS based on both theoretical and
      research perspectives. This section includes a critical review of CBT therapies
      for IBS and provides a model of CBT for IBS. The second section provides the
      clinician with practical information concerning the application of cognitive
      behavioral group therapy for IBS. Possible scripts and case examples are
      incorporated into this section to highlight factors that may arise in working
      with IBS patients relative to other clinical groups. The second section also
      contains themes that are suggested content areas for group sessions. Contingent
      on the formulation of the presenting or emerging issues and goals, the order and
      inclusion of themes can be changed to fit the particular needs of a given group.
      Finally, this section provides initial preliminary data from a randomized
      controlled study that is suggestive of the efficacy of cognitive-behavioral
      therapy for IBS.

PMID- 9563240
TI  - The rationale and foundations of group psychotherapy for women with metastatic
      breast cancer.
AB  - Group psychotherapy has become an important modality of intervention in
      contemporary psychooncology. This article reviews and describes the rationale and
      foundations for group psychotherapy for women with metastatic breast cancer. It
      emerges from a replication study of an earlier study performed by Spiegel
      (Spiegel, Bloom, Kraemer & Gottheil, 1989), which demonstrated that participation
      in structured group psychotherapy resulted in improved psychosocial adjustment
      and a significant survival effect on women with metastatic breast cancer. Other
      intervention studies, psychosocial effects of psychosocial interventions, as well
      as psychosocial variables associated with the course of illness, are described.
      The contribution of existential considerations in psychotherapy is also
      articulated as a component of the group-supportive expressive intervention.
      Clinical illustrations, emerging from ongoing treatment groups, are used to
      demonstrate theoretical concepts.

PMID- 9563241
TI  - Staff support groups for high-stress medical environments.
AB  - Recent changes in health care delivery have added new demands to the already
      stressful work of medical staff, which makes the benefits of staff support groups
      all the more cogent. The author describes a conceptual approach to such groups
      and analyzes the systems issues that need to be understood to penetrate a complex
      institution successfully. Staff stressors are outlined along with the staff's
      psychological responses. Specific goals for support groups are considered and the
      profound technical differences between psychotherapy and support groups are
      delineated. The developmental stages of staff groups and their associated themes
      are described in tandem with practical guidelines about starting, maintaining,
      and terminating such groups. Special requirements of leadership style and related
      countertransference issues are reviewed.

PMID- 9563242
TI  - 1997 Doolin Memorial Lecture. Medical manpower at the millenium--what kind of
      doctors in what kind of hospitals?

PMID- 9563243
TI  - Current views on Helicobacter pylori eradication therapy.

PMID- 9563244
TI  - Hypertension--is adequate control possible?

PMID- 9563245
TI  - Controlling antibiotic use: protecting an endangered medical resource.

PMID- 9563246
TI  - Women and smoking.

PMID- 9563248
TI  - Immunization and cot death.

PMID- 9563247
TI  - Insulin analogues--patient preference may drive prescribing.

PMID- 9563249
TI  - Detection of benzodiazepine abuse in opiate addicts.
AB  - There is an increasing problem with benzodiazepine co-abuse in the opiate
      dependent population of Dublin. The importance of early detection of this co
      abuse is essential as there is an increased risk of dangerous injecting practices
      such as sharing of needles and criminality in those who co-abuse benzodiazepines
      and opiates. This study was carried out in the National Drug Treatment Centre,
      Dublin. It aims to describe the current difficulties in identifying the co-abuse
      of short acting benzodiazepines including flunitrazepam in a cohort of opiate
      dependent patients. Using a sample of those attending the clinic it was
      discovered that standard methods of urinalysis failed to identify 10% of co
      abuse. For those patients whose abuse of flunitrazepam is undetected on
      screening, clinical interventions which aim to minimise the consequence of the co
      abuse and reverse the chaotic drug using patterns fail to be put in place at the
      earliest possible time.

PMID- 9563250
TI  - Acute hospital admission systems: problems experienced by general practitioners.
AB  - This study was undertaken to examine the existing system of access for general
      practitioners in arranging acute admissions to three general hospitals in the
      Southern Health Board (SHB) area. One hundred and twenty eight patients were
      admitted to the three hospitals over a one week period. General practitioners
      were surveyed on the process of admission for each patient. Response rate was
      118/128 (92.2%). Hospital A had 53 admissions, Hospital B had 41 admissions and
      Hospital C had 24 admissions. In total, 30/118 (25.4%) admissions took over one
      hour to arrange, of these 23 (76.7%) were admitted to Hospital A, 4 (13.3%) were
      admitted to Hospital B and 3 (10.0%) were admitted to Hospital C. The admission
      sister was responsible for confirming the route of admission in 102 (86.4%) of
      cases. In Hospital A, 23/53 (43.4%) patients were referred to Accident and
      Emergency (A&E) for assessment prior to admission, 4/41 (9.8%) were referred in
      Hospital B, and 2/24 (8.3%) in Hospital C. In the light of current findings,
      possible alternatives to the current acute admissions system are discussed.

PMID- 9563251
TI  - Group B streptococcus (GBS) colonisation among expectant Irish mothers.
AB  - Group B streptococci (GBS) have been recognised for more than three decades as a
      serious cause of perinatal morbidity and neonatal mortality. The aim of this
      study was to accurately determine the prevalence of GBS carriage and the serotype
      distribution among pregnant Irish women. 504 women attending antenatal clinics
      had two swabs (one perianal and one low vaginal) taken in the last four weeks of
      their pregnancy. These were placed in Todd Hewitt broth and then subcultured onto
      solid media. Serotyping of the isolates was performed by the Central Public
      Health Laboratory, London. GBS colonised women were treated with prophylactic
      antibiotics in labour and their infants received prophylaxis for 48 hours. 129
      women (25.6%) were found to be asymptomatically colonised with GBS. Dual site
      screening (low-vaginal and perianal) identified 5% more GBS carriers than one
      site would have done. Serotypes identified included types I (30%), II (17%), III
      (30%), IV (1%) and V (9%). GBS colonisation is very common in Irish pregnant
      women and therefore a strategy for management in pregnancy ought to be developed
      in order to reduce the recognised occurrence of neonatal morbidity and mortality
      caused by this organism.

PMID- 9563252
TI  - Evaluation of a 20 minute 14C urea breath test for the diagnosis of Helicobacter
      pylori infection.
AB  - The use of 14C-urea breath testing for diagnosis of Helicobacter pylori infection
      in gastric mucosa has gained widespread acceptance and utilisation. We evaluated
      a 14C urea breath test (UBT) in 116 patients undergoing endoscopy. Seventy four
      patients were administered 185 kBq (5 mCi-conventional dose), and 42 patients
      reduced dose (92.5 IBq, 2.5 mCi) of 14C-urea. All were tested for H. pylori using
      culture, direct microscopy of gastric biopsies and histological evaluation of
      paraffin stained sections. Using the mean + three standard deviations as the cut
      off value, a sensitivity of 96% and specificity of 100% was found for the
      conventional dose test. At reduced dose, sensitivity was 100% and specificity
      96%. Positive and negative predictive values were 100% and 93% for the
      conventional dose test, and 96% and 100% for testing at reduced dose. We conclude
      that the UBT is a simple, non-invasive and useful diagnostic alternative for
      detection of H. pylori in infected patients. We advocate its use in patients less
      than 45 years of age without alarm symptoms, and also in cases where the need for
      endoscopic evaluation is not vital, such as after eradication therapy.

PMID- 9563253
TI  - The legislative position governing patient access to medical records.

PMID- 9563254
TI  - Spontaneous passage of giant salivary calculus.

PMID- 9563255
TI  - Hospital doctors: know cost of drugs and NARA values.

PMID- 9563256
TI  - Should pregnant women be screened for drugs of abuse?

PMID- 9563258
TI  - Clinical advances in anti-retroviral treatment.

PMID- 9563257
TI  - Blind faith revisited.

PMID- 9563259
TI  - Laparoscopic splenectomy in a community setting.

PMID- 9563260
TI  - Health and economic impact of cigarette smoking in South Carolina, 1995.

PMID- 9563261
TI  - Women, medicine, and health: a sociological perspective.

PMID- 9563262
TI  - How South Carolina Physicians rate managed care: a South Carolina Family Practice
      Research Consortium study.

PMID- 9563263
TI  - Primary prevention of myocardial infarction: a role for electron beam computed
      tomography (EBCT)?

PMID- 9563265
TI  - Benign mesenteric schwannoma: MRI findings.
AB  - Accurate differentiation of retro- or intraperitoneal localization of a primary
      abdominal tumor by US and CT is often difficult. In our case an abdominal mass
      was incidentally discovered and identified as a typical benign schwannoma, but
      with a very atypical location in the mesentery. We found that MRI was a valuable
      adjunct to CT for exact tumor localization.

PMID- 9563264
TI  - Caroli's syndrome.
AB  - We report the case of a two-year-old girl presenting with recurrent episodes of
      fever and hepatomegaly. High resolution ultrasound (US) and computed tomography
      (CT) of the liver show dilated intrahepatic bile ducts with bridge formation and
      intraluminal protrusions. The extrahepatic bile duct is normal. The diagnosis of
      irregular dilated bile ducts with signs of cholangitis and cholangiolitis is
      proved by liver biopsy. The histologically associated congenital liver fibrosis
      in our patient enter into the Caroli's syndrome. We illustrate the high
      resolution US and the CT findings in this case.

PMID- 9563266
TI  - Dehiscent jugular fossa associated with vertigo.
AB  - In a patient with two widely separated episodes of vertigo CT identified a high
      and medially directed jugular fossa with dehiscence extending to the internal
      auditory meatus and the vestibular aqueduct. The question of whether the
      radiological findings were incidental or directly related to the patient's
      symptoms is discussed.

PMID- 9563267
TI  - Aneurysmal bone cyst of the zygomatic arch.
AB  - We present a case of aneurysmal bone cyst in the jaw investigated with plain
      film, US, computed tomography (axial, precontrast) and magnetic resonance (1
      Tesla, axial T1 weighted before and after Gadolinium administration, axial and
      coronal T2-weighted after Gadolinium administration). The zygomatic arch is a
      very rare location for an aneurysmal bone cyst: as far as we know, only a few
      cases are found in the literature.

PMID- 9563268
TI  - Amiodarone induced pulmonary toxicity.
AB  - We report on a case of complicated long-term amiodarone therapy. CT demonstrated
      high attenuation pleural-parenchymal lesions and increased liver and spleen
      density. This article stresses the important role of CT in the diagnosis of
      amiodarone related disease.

PMID- 9563269
TI  - [Undifferentiated sarcoma of the ulna in a patient with Paget's disease].
AB  - The development of bone sarcoma in a patient with Paget disease is a classic but
      rare event. The authors describe the XR, CT and MR features of an
      undifferentiated Paget sarcoma arising in the proximal ulna, a very rare location
      of this tumoral complication. Clinical symptoms, radiological pattern and
      epidemiology are discussed. In every Paget patient presenting with a new or
      different pain, with or without mass effect, the radiologist has to search for
      signs of sarcomatous transformation, i.e. cortical osteolysis, soft tissue mass
      and sometimes an associated fracture.

PMID- 9563270
TI  - Ultrasound studies in ectopic pregnancies.
AB  - Early diagnosis of ectopic pregnancy reduces the mortality and morbidity
      associated with the disease, and the morbidity associated with the therapy. When
      diagnosis was limited to the cases presenting with tubal rupture, salpingectomy
      was the only possible treatment. If ectopic pregnancy can be diagnosed earlier,
      clinicians are able to use new therapies such as laparoscopic microsurgery or
      medical therapy with methrotrexate, which are less invasive and less tissue
      destructive. Transvaginal ultrasound has proven to be an essential tool in the
      early diagnosis of ectopic pregnancy. Colour Doppler capacities further enhance
      the diagnostic sensitivity of transvaginal ultrasound for the early recognition
      of abnormal and normal intrauterine pregnancy, and small extrauterine masses. The
      aim of this paper is to provide an overview of the major sonographic signs and
      pitfalls in the ultrasound diagnosis of ectopic pregnancy.

PMID- 9563271
TI  - [Mucosecretory and papillary intraductal tumors of the pancreas:
      clinicopathological considerations and radiological aspects including computed
      tomography symptomatology].
AB  - Intraductal papillary-mucinous tumor of the pancreas (IPMT) is an uncommon
      entity, defined as an intraductal papillary proliferation of mucin-producing
      epithelial cells. Since the original description of the disease by Ohhashi in
      1982, the definition and the classification of the disease has remained confused
      until the recently published classification of the World Health Organisation
      (WHO). The purpose of this article is therefore to report the clinico
      pathological features of IPMT according to the WHO classification, to illustrate
      the radiological features especially the computed tomographic signs and to
      discute of the treatment.

PMID- 9563272
TI  - Effect of an inhibitor of glucosylceramide synthesis on cultured human
      keratinocytes.
AB  - Glucosylceramide (GlcCer) is a major glycosphingolipid component of epidermis,
      which is thought to be related to the barrier function of skin permeability.
      However, the role of glycosphingolipids in keratinocyte growth and
      differentiation has not been fully clarified. It has been reported that D-threo-1
      phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), an inhibitor of GlcCer
      synthase (EC 2.4.1.80), depletes cells of glycosphingolipids. This inhibitor has
      been used as a tool for elucidating their functions. In the present study, the
      effect of PDMP on cultured normal human keratinocytes was investigated. The cells
      were treated with various concentrations of PDMP. Forty-eight hours later cell
      growth, thymidine incorporation, and lipid content were studied. The cell growth
      and the incorporation of thymidine into cells were inhibited by PDMP in a dose
      dependent manner. The synthesis of GlcCer was strongly inhibited by PDMP
      treatment, whereas no significant changes in ceramide level were observed. We
      concluded that GlcCer in epidermis may play an important role in regulating
      epidermal growth and suggested that PDMP may be beneficial for treating
      proliferative skin disorders in the future.

PMID- 9563273
TI  - The expression of endothelin-1 and its binding sites in mouse skin increased
      after ultraviolet B irradiation or local injection of tumor necrosis factor
      alpha.
AB  - Endothelin (ET)-1 is a 21-amino acid peptide which has vasoconstrictor and growth
      regulatory activity. Recently, cultured keratinocytes have been reported to
      express ET-1 and its receptor when irradiated by ultraviolet (UV) B. In order to
      further understand the role of ET-1 in vivo during UVB-induced inflammation, we
      examined the localization, intensity and time course of the expression levels of
      ET-1 and its binding sites in UVB-exposed BALB/c mouse skin. Frozen and paraffin
      sections prepared from mouse skin 48 h after treatment with UVB irradiation (0.36
      or 0.72 J/cm2) or after injection with tumor necrosis factor (TNF)-alpha (1.0
      microgram) or interleukin (IL)-1 alpha (0.05 microgram) were incubated with
      monoclonal anti-ET-1 IgG and then visualized by peroxidase staining. In normal
      skin, faint ET-1 immunoreactivity was observed in the epidermis, pilosebaceous
      structures and blood vessels. Upon exposure to UVB irradiation or administration
      of TNF-alpha injection or IL-1 alpha injection, such immunoreactivity was found
      to be significantly enhanced. Subsequently, the frozen sections were incubated
      with 125I ET-1 for 30 min, and visualized by autoradiographic technique. In
      normal skin, ET-1 weakly bound to the skin, while UVB irradiation and TNF-alpha
      injection significantly enhanced ET-1 binding in the epidermis, pilosebaceous
      structures and blood vessels. Time course experiments (1, 2, 4 and 7 days)
      indicated that ET-1 immunoreactivity and ET-1 binding peaked 1 or 2 days after
      UVB irradiation or TNF-alpha injection. These results suggest that the up
      regulated expression of ET-1 and its binding sites in the epidermis and
      pilosebaceous structures may act as an autocrine/paracrine factor during UVB
      induced inflammation.

PMID- 9563274
TI  - The effect of glycolic acid on cultured human skin fibroblasts: cell
      proliferative effect and increased collagen synthesis.
AB  - Glycolic acid peeling is known to improve photoaging processes such as wrinkling
      and roughness, but this effect has not been clearly defined, even though
      functional activation of fibroblasts has been suggested. The study was aimed to
      determine the effects of glycolic acid and malic acid (AHA: alpha hydroxy acid)
      on cultured dermal fibroblasts. Whether it directly increases cell proliferation
      may be an important factor influencing the production of extracellular matrix
      such as type I collagen. Cultured human skin fibroblasts were treated for 24
      hours with glycolic acid and malic acid at different concentrations (10(-4), 10(
      5), 10(-6) M), and cell proliferation was measured by MTT assay. Then
      quantitative analysis of collagen synthesis was performed by PICP (Procollagen
      Type I C-peptide) enzyme immunoassay and radioisotope (3H-proline) labelled
      collagen assay. The results showed increased cell proliferation and collagen
      production in response to glycolic acid in a dose dependent manner. The range of
      cell proliferation and collagen production were significantly higher with
      glycolic acid treatment than with malic acid or control. It was suggested that
      the favorable effects of glycolic acid treatment on aging skin were mediated by
      increased cell proliferation in addition to functional activation of fibroblasts.

PMID- 9563275
TI  - Spongiotic annular erythema in SS-A/SS-B antibody negative Sjogren's syndrome.
AB  - We reported four cases of Sjogren's syndrome (SjS) who manifested a new type of
      annular erythema that differs from the previously described annular erythema seen
      in anti-SS-A/SS-B antibody positive SjS in both clinical and histological
      findings. Characteristic histological features are the presence of spongiotic
      changes around the acrosyringium and perivascular lymphocytic infiltration
      without liquefaction degeneration or epidermal change, suggesting lupus
      erythematosus. No complement or immunoglobulin depositions are demonstrated along
      the basement membrane zone or around blood vessels. Clinically, this type of
      erythema usually appears on the trunk or extremities with itchy sensations,
      especially in summer, which contrasts with the preferential occurrence of the
      previously reported SjS related annular erythema on the facial skin in winter.
      Immunologically, all four cases lacked anti-SS-A and anti-SS-B antibodies, but
      possessed positive anti-microsome antibodies or thyroid tests. In three cases,
      metal allergy was demonstrated by patch test, which might suggest that the sweat
      duct is the primary target of excreted metals in this condition and that
      underlying SjS might play some role in the higher prevalence of metal allergy or
      in induction of sweat duct injury, similar to the interstitial nephritis which is
      now thought to be an exocrine manifestation of SjS.

PMID- 9563276
TI  - Factors influencing psoriasis: an analysis based upon the extent of involvement
      and clinical type.
AB  - A variety of external stimuli are accepted as important in modifying the severity
      of psoriasis. We sought to determine whether there is any difference in the
      influence of external factors on psoriasis in relation to extent of involvement
      or clinical type. A total of 870 psoriasis patients seen between 1982 and 1995
      were categorized as mild, moderate, or severe on the basis of extent of the
      disease, and as guttate, nummular/plaque, or exfoliative/generalized pustular
      according to clinical type. We then performed a questionnaire survey concerning
      the influence of external factors such as seasonal changes, sunlight, stress, and
      pregnancy. These data sets were combined and analysed. The majority of patients
      stated favorable effects of summer, sunlight, and pregnancy and adverse effects
      of winter and stress. A statistically significant correlation was noted between
      the extent of psoriasis and the proportion of patients stating that their disease
      worsened at times of psychological stress (p < 0.01). We confirmed that psoriasis
      patients with more extensive involvement experience greater fluctuations in their
      condition, notice these changes, and therefore relate them to psychological
      stress.

PMID- 9563277
TI  - A clinical observation of scleredema adultorum and its relationship to diabetes.
AB  - Scleredema may occur secondarily to diabetes or independently. The course of
      scleredema is not known in either type. Twenty-one scleredema patients were
      included in this study (13 females, 8 males). The patients were divided into two
      groups according to the presence or absence of diabetes. In the group (11
      patients) of scleredema which was secondary to diabetes, lesions were partially
      improved in 5 patients who had controlled diabetes, although it was difficult to
      control diabetes with insulin or oral hypoglycemics in such patients. Scleredema
      appeared insidiously in nine of these eleven patients. The posterior neck was
      involved, but the face was not. In patients without diabetes, the scleredema
      lesions began acutely in eight of ten of them. The course of the disease was
      usually stationary rather than showing acute improvement. Facial involvement was
      found in half of all the patients. In conclusion, scleredema patients with
      diabetes may improve if their diabetes is controlled, and facial involvement may
      be related to scleredema without diabetes.

PMID- 9563278
TI  - Reappraisal of Ikeda's classification of alopecia areata: analysis of 356 cases
      from Chandigarh, India.
AB  - Three hundred and fifty six patients (234 males, 122 females) with alopecia
      areata were classified according to Ikeda's classification. The common type of
      alopecia areata was most frequently seen in 239 (67.13%) patients, followed by
      atopic in 60 (16.85%), prehypertensive in 48 (13.4%), and autoimmune/endocrine in
      9 (2.52%) patients. Severe alopecia did not occur with a higher frequency in
      atopic or endocrine/autoimmune alopecia areata than in the common type (p >
      0.05). Prehypertensive alopecia areata had the lowest frequency of severe
      alopecia in the present study. The odds for developing severe alopecia were
      highest (2.6) when onset was before 16 years of age, followed by female sex
      (2.12), atopy (0.86), autoimmune/endocrine (0.53), and prehypertensive (0.28)
      types. Alopecia areata should be broadly classified as childhood (< 16 years) and
      adult onset with subtypes of atopic, autoimmune/endocrine, and common type under
      both. The prehypertensive type should be combined with the common type of
      alopecia areata.

PMID- 9563279
TI  - The effectiveness of modified ingram therapy compared with severity of psoriasis.
AB  - To treat cases of psoriasis, various modifications of the original Ingram method
      were tested for increased effectiveness and minimized side reactions. Our
      modified method consists of 0.1-0.5% anthralin ointment application and selective
      UVB phototherapy with adjunctive warm water bath and the application of
      emollients. The object of this study was to evaluate the effectiveness and
      duration of remission in response to our modified Ingram method and compare the
      data with the severity of psoriasis. The clearing rate was higher and the failure
      rate was lower in the moderate group. The number of occasions on which therapy
      was used and the duration of this therapy were greater in the severe group, but
      there were no significant differences except for the number of occasions of
      therapy to the trunk. Fifty-eight percent of the moderate group did not relapse
      in more than one year, but 63% of the severe group relapsed within six months.
      The results of this study showed that the modified Ingram regimen is an effective
      therapeutic modality in psoriasis, especially in the moderate group.

PMID- 9563280
TI  - A case of Post-kala-azar dermal leishmaniasis.
AB  - Only a few cases of Post-kala-azar dermal leishmaniasis have been reported in
      Japan, especially recently. We describe a case of a 32-year-old woman who
      developed rose-colored nodules on her forearms two years after Kala-azar. A skin
      biopsy specimen from a nodule revealed not only granulomatous changes but also
      many amastigotes of Leishmania donovani in macrophages. Rose-colored nodules were
      also distributed on her face and neck. Treatment with antimony compound was very
      effective.

PMID- 9563281
TI  - Epithelioid leiomyosarcoma of the skin.
AB  - We report a case of epithelioid leiomyosarcoma that developed on the nose of a 55
      year-old Korean male over a one year period. The lesion was a pea sized, firm,
      erythematous, painless nodule with erosion in the center. Histologic examination
      revealed short spindled cells with blunt-ended nuclei and pleomorphic round to
      oval epithelioid cells with abundant eosinophilic cytoplasm that were
      perivascular and densely packed in the dermis. Immunostaining for desmin was
      negative, although stains for vimentin and smooth muscle actin were both strongly
      positive.

PMID- 9563282
TI  - An unusual female melanoma patient with late metastases to both skin and ovaries.
AB  - We presented an unusual case of cutaneous and bilateral ovarian metastases of
      malignant melanoma. There was no previously identifiable cutaneous or mucous
      lesion or teratoid element. Past history revealed that the patient had undergone
      removal of a blackish, elevated, irregular shaped tumor from the right arm eleven
      years previously. This lesion was considered to be the primary melanoma;
      therefore, it was thought to be very unusual as metastasis occurred in both the
      skin and ovaries after an eleven year disease-free interval.

PMID- 9563283
TI  - Psoriasis in a patient with immunoblastic lymphadenopathy (IBL)-like T cell
      lymphoma: a possible candidate of systemic release of interferon gamma.

PMID- 9563284
TI  - Systemic administration of hochu-ekki-to (bu-zhong-yi-qi-tang), a Japanese
      Chinese herbal medicine, maintains interferon-gamma production by peripheral
      blood mononuclear cells in patients with mycosis fungoides.

PMID- 9563285
TI  - A nevocellular nevus consisting mostly of nevic corpuscles.
AB  - A scalp tumor from a 24-year-old male presenting unusual histological finding is
      described. The tumor was mostly composed of corpuscles resembling Meissner
      tactile bodies and contained almost no other components. Immunohistochemical
      studies revealed the tumor cells to be positive for S-100 protein and neuron
      specific enolase, so we considered the tumor to be an unusual nevocellular nevus
      mostly comprised of nevic corpuscles.

PMID- 9563286
TI  - Fixed drug eruption due to afloqualone: the first reported case.

PMID- 9563287
TI  - Recognition of facial expressions of emotion by children with attention-deficit
      hyperactivity disorder.
AB  - Fifty children and adolescents were tested for their ability to recognize the 6
      basic facial expressions of emotion depicted in Ekman and Friesen's normed
      photographs. Subjects were presented with sets of 6 photographs of faces, each
      portraying a different basic emotion, and stories portraying those emotions were
      read to them. After each story, the subject was asked to point to the photograph
      in the set that depicted the emotion described. Overall, the children correctly
      identified the emotions on 74% of the presentations. The highest level of
      accuracy in recognition was for happiness, followed by sadness, with fear being
      the emotional expression that was mistaken most often. When compared to studies
      of children in the general population, children with ADHD have deficits in their
      ability to accurately recognize facial expressions of emotion. These findings
      have important implications for the remediation of social skill deficits commonly
      seen in children with ADHD.

PMID- 9563288
TI  - Effect of reinforcement on facial responsivity and persistence in children with
      attention-deficit hyperactivity disorder.
AB  - Children with Attention Deficit-Hyperactivity Disorder (ADHD) may learn poorly
      under conditions of inconsistent (partial) reinforcement because they are easily
      frustrated and fail to develop persistence. To test this hypothesis, a nonsense
      word spelling task was used with 22 ADHD and 20 control children to investigate
      the effects of partial and continuous reinforcement on facial responsivity
      (frustration measure), words spelled correctly (learning performance measure),
      and persistence ratings. Partially reinforced ADHD children manifested higher
      levels of frustration in both acquisition and extinction than any other group and
      gave significantly lower persistence ratings across acquisition than partially
      reinforced control children. ADHD children spelled fewer words correctly than
      controls, regardless of reinforcement schedule. These findings suggest that
      partial reinforcement training develops persistence in normal but not ADHD
      children. The findings have theoretical implications for the etiology of ADHD as
      well as practical implications for designing behavior modification programs to
      treat ADHD.

PMID- 9563289
TI  - Right hemisphere damage impairs the ability to process emotional expressions of
      unusual faces.
AB  - Patients with focal brain damage, right and left hemisphere damage, and
      nonpatient controls were asked to match photographs of emotion expressions that
      were depicted in unusual (line drawings, strange, and schematic) and normal
      (usual) representations of faces with the target emotion expressions of normal
      face. Nonpatient controls were significantly superior to right hemisphere damaged
      patients in matching photographs of emotion expressions that were depicted in
      line drawings of normal face and schematic face.

PMID- 9563290
TI  - Hemifacial asymmetry in emotion expressions.
AB  - We examined asymmetry in posed facial expression of emotions: happy and sad.
      Hemifacial composite photographs, left-left and right-right, were prepared, and
      subjects rated these for intensity of expressed emotion. Overall, left-left
      composites were judged to have expressed emotions relatively more intensely than
      the right-right composites. The significant Sex x Emotion interaction revealed
      that female expressors were judged as more expressive than male expressors in
      expressing sad facial emotion. Sex difference in expression of happy facial
      emotion was not significant.

PMID- 9563291
TI  - Decoding of facially expressed emotions in patients with psychosomatic
      gastrointestinal disorders.
AB  - The hypothesis that individuals with psychosomatic conditions are lacking in
      empathy was tested by investigating decoding abilities of facially expressed
      emotions. Fourteen subjects with psychosomatic gastrointestinal disorders and 14
      matched controls participated. Slides of one male and one female model's facial
      expressions of anger, disgust, fear, happiness, sadness, and surprise, and a
      neutral face, were presented to subjects, with exposure durations of 1/60, 1/15,
      and 4 seconds. Subjects had to decide whether the face presented was neutral or
      expressed one of the basic emotions. There were no significant group differences
      in decoding neutral expressions, but significant differences resulted in decoding
      emotional expressions. This was mainly due to the significantly poorer
      performance of the psychosomatic group in decoding disgust. Subjects' responding
      was found to be reliable. The findings show that at least certain subgroups of
      psychosomatic patients tend to misinterpret another person's facial expressions
      that signal unpleasantness or interpersonal conflict.

PMID- 9563293
TI  - Recognition of facial expressions of emotion by Chinese adults with mental
      retardation.
AB  - We compared the ability of Chinese adults with mental retardation and
      nonhandicapped Chinese children to recognize the six basic facial expressions of
      emotion. Each subject was told a story identifying an emotion, presented with an
      array of six photographs of basic facial expressions of emotion, and asked to
      point to the photograph that depicted the story's emotion. Results showed that
      the children were more accurate than the adults in recognizing facial expressions
      of emotion except happiness on which both groups achieved 100% accuracy.
      Surprise, fear, anger, and disgust were confused most often by both groups.
      Recognition proficiency was not significantly correlated with age in the children
      or with IQ in the adults. Our results partially replicated those reported in
      earlier studies with non-Chinese individuals with mental retardation and raised
      the possibility that there may be cultural influences on a person's ability to
      recognize facial expressions of emotion.

PMID- 9563292
TI  - Abnormal facial emotion recognition in depression: serial testing in an ultra
      rapid-cycling patient.
AB  - Normal subjects use the right insula and bilateral anterior temporal and
      prefrontal cortices to recognize the emotion expressed in a human face. Mood
      disorder subjects have a selective deficit in recognizing human facial emotion.
      Brain imaging studies show that they fail to activate the right insula to the
      same degree as controls, even when accurately assessing facial emotion. Many
      issues remain, however, including whether the facial emotion recognition errors
      in mood disorder subjects are state dependent or persist during normal mood
      states (and, thus, reflect a trait abnormality). To probe this issue, we
      repeatedly studied a male bipolar II patient's ability to recognize faces'
      emotional content. This patient made significantly more errors in facial emotion
      recognition during the depressed state. He also demonstrated a significant
      negative bias when he was depressed compared with nondepressed states. This case
      study demonstrates the state dependency of the defect in human facial emotion
      recognition.

PMID- 9563294
TI  - Lymphedema after cancer.

PMID- 9563295
TI  - Early intervention to block HIV.

PMID- 9563297
TI  - Surgery and memory.

PMID- 9563298
TI  - Too little vitamin D?

PMID- 9563296
TI  - Should you take St. John's Wort?

PMID- 9563299
TI  - Controlling blood pressure without drugs.

PMID- 9563300
TI  - Most elderly women ok living alone.

PMID- 9563301
TI  - Treating ulcers caused by NSAIDs.

PMID- 9563302
TI  - Apnea advances.

PMID- 9563303
TI  - Suicide link with blood pressure drug unproven.

PMID- 9563304
TI  - Low-dose estrogen.

PMID- 9563305
TI  - Dental health education for pre-school carers.

PMID- 9563306
TI  - Factors affecting dental surgery assistants' job satisfaction in general dental
      practice.
AB  - Reported studies suggested that job satisfaction, was low among non-operating
      dental auxiliaries. Clearly this might affect the quality of their work. The
      study reported in the present article evaluated dental surgery assistant (DSA)
      job satisfaction in general dental practices in the northwestern region of
      England. An initial qualitative study determined the factors that DSAs thought
      affected their job satisfaction and these were evaluated in a quantitative study.
      Although the majority of DSAs found their work satisfying and enjoyable, a number
      found some aspects unsatisfactory and changes are proposed which may improve the
      quality of their working lives.

PMID- 9563307
TI  - Computers in general dental practice. Links with the dental practice board.

PMID- 9563308
TI  - Developing oral health promotion in general dental practice in East London.

PMID- 9563309
TI  - Dental health for pre-school carers in the Dudley area.

PMID- 9563310
TI  - MDHA expanded functions survey. Report of the findings.

PMID- 9563311
TI  - Memories of the dental school will keep its spirit alive.

PMID- 9563312
TI  - Law and ethics: the elements of a contract. The tie that binds is not always
      blessed!

PMID- 9563313
TI  - Managed care in dentistry: ethical implications, ethical challenges.

PMID- 9563314
TI  - The bacterial viruses of the oral pathogen Actinobacillus actinomycetemcomitans
      (Aa).

PMID- 9563315
TI  - Role of cytokines in periodontal diseases.

PMID- 9563316
TI  - Joint vibration analysis. Part II.

PMID- 9563317
TI  - Prevalence of temporomandibular joint pain in a population seeking orthodontic
      treatment.

PMID- 9563318
TI  - The Loudon Chateau repositioning appliance.

PMID- 9563319
TI  - Functional forum: a laboratory survey of 1,250 Twin Blocks.
AB  - In summary, the cosmetic Twin Block appliance delivers a high degree of treatment
      satisfaction to both clinicians and patients (parents, too) with relatively fast
      correction that can be seen by the patient. Speed of treatment, great aesthetics
      compared to other alternatives, and the comfort during full-time wear meet the
      treatment challenges of today. Education is the key ingredient in developing your
      expertise with Twin Block treatment programs. I would like to encourage doctors
      to use an experienced laboratory and communicate the individual needs of each
      patient to the technician involved in the fabrication of each appliance.

PMID- 9563320
TI  - A basic approach to management of medical emergencies in the dental office.

PMID- 9563321
TI  - "Treatment planning" your personal economics.

PMID- 9563322
TI  - Employee performance evaluation and compensation review.

PMID- 9563323
TI  - Medical emergencies in the dental office--Part 2.

PMID- 9563325
TI  - Oral rehabilitation of a patient with amelogenesis imperfecta.
AB  - A patient with Type I hypoplastic patterned amelogenesis imperfecta, subtype D,
      presented for prosthodontic evaluation. This article describes the developmental
      and pathophysiological background of this disease. A clinical report describing
      the diagnosis, treatment planning, and dental rehabilitation of the patient is
      reviewed.

PMID- 9563324
TI  - Prosthodontic rehabilitation using surgical space modification.
AB  - Treatment using a Le Fort I osteotomy and sequential prosthodontic rehabilitation
      is presented. This treatment combination is a viable alternative therapy for the
      severe extrusion of posterior maxillary dento-osseous segments.

PMID- 9563326
TI  - Immediate maxillofacial prosthodontic rehabilitation after radical mid-face tumor
      resection.
AB  - Mid-facial surgical defects can adversely affect a patient's esthetics and
      psychological well-being. Fabrication of a definitive mid-facial prosthesis can
      be a time-consuming procedure. It is crucial to minimize the time between the
      tumor resection and initial prosthetic rehabilitation. This article describes a
      method for rapid fabrication of a transitional facial prosthesis for mid-facial
      defects.

PMID- 9563327
TI  - Intrusion of teeth in the combination implant-to-natural-tooth fixed partial
      denture: a review of the theories.
AB  - This article reviews the literature dealing with the combination implant-to
      natural-tooth-supported fixed partial denture. The restoration of masticatory
      function with a combination implant-to-natural-tooth fixed partial denture is
      associated with a variety of undesirable clinical sequelae, including the
      breakage of implant components, damage to the abutment teeth, or intrusion of the
      abutment teeth. Theories regarding intrusion of abutment teeth combined with
      implants for fixed partial dentures are only speculative. Several theories are
      presented to explain the intrusion of natural teeth in association with implant
      to-natural-tooth fixed partial dentures. One of the first theories was based on
      the idea that a lack of normal stimulation of the periodontal ligament produces
      atrophy of the periodontal ligament and intrusion of the tooth. The remaining
      theories relate to excessive forces being placed on the natural tooth, resulting
      in movement of the tooth to a less stressful position. These forces are placed on
      the tooth by differential energy dissipation, mandibular flexion and torsion,
      flexion of the fixed partial denture framework, impaired rebound memory, debris
      impaction or microjamming, or ratchet effect related to the use of precision
      attachments. Based a review of the literature, a philosophy for treating
      combination implant-to-natural-tooth restorations is presented.

PMID- 9563328
TI  - Erosion caused by gastroesophageal reflux: diagnostic considerations.
AB  - Dental erosion occurs with a high prevalence in the general population, but its
      impact on prosthodontic care is often unrecognized. The etiology of dental
      erosion is difficult to establish because it may result from a variety of causes
      and may have different presentations. Our purpose was to review the literature
      relevant to dental erosion and to report a patient presentation in which an
      unusual pattern of severe erosion was the dental manifestation of asymptomatic
      gastroesophageal reflux disease.

PMID- 9563329
TI  - Introduction of a denture injection system for use with microwaveable acrylic
      resins.
AB  - Recently, an injection system for use with microwaveable denture base resins was
      introduced. Preliminary evaluation of this system was performed a university
      based dental laboratory. This article provides a description of the complete
      denture fabrication technique, as well as observations regarding its design and
      practicality.

PMID- 9563330
TI  - A bimaxillary sports mouthguard: a modified technique.
AB  - The bimaxillary mouthguard provides enhanced protection for a participant in
      contact sports. This article describes the fabrication of a polyvinylacetate
      polyethylene (PVAc-PE) bimaxillary mouthguard in which the connection of the
      maxillary and mandibular components is reinforced by pressure thermoforming a 2
      mm PVAc-PE sheet over the labial and buccal portions of the mouthguard.

PMID- 9563332
TI  - Data collection in periodontal treatment planning.
AB  - Providing successful dental care is a daily challenge. Techniques to improve our
      own technical skills are of obvious value, however careful consideration of all
      the available facts help us to maximize the benefit of our technical skills. We
      are frequently limited by the conditions and attitudes that are attached to our
      patients. I suggest we need to recognize those limitations and convey them to
      those that we are caring for. Our formulation of an accurate treatment plan is
      the result of consideration of as many of the factors influencing the disease as
      can be discovered.

PMID- 9563331
TI  - New developments in endodontic therapy: endodontic instrumentation.

PMID- 9563333
TI  - Antibiotics: an adjunct to endodontic therapy.

PMID- 9563334
TI  - Antibiotics in periodontal therapy--current status.

PMID- 9563335
TI  - Dental knowledge survey of NM dental patients.

PMID- 9563336
TI  - Full mouth reconstruction. Utilizing fiber-reinforced framework and Ceromer
      restorations in combination with pressed ceramic technology.
AB  - The final results of this case were pleasing to the patient and the dentist (Fig.
      5). The missing teeth had been replaced, function had been restored, the anterior
      crowding had been eliminated (Fig. 6), and the bioesthetic symmetry and harmony
      had been restored (Fig. 7). The patient reported a dramatic increase in self
      confidence with her peers. (Fig. 8) Special thanks to Michael Milner for the
      excellent Laboratory work provided for this case.

PMID- 9563337
TI  - Revised antibiotic prophylaxis: does a standard of care exist?

PMID- 9563338
TI  - New Mexico Dentist/Hygienist Distribution.

PMID- 9563339
TI  - Use of large bone grafts with dental implants.

PMID- 9563340
TI  - Implant site preparation.

PMID- 9563341
TI  - Surgical complications related to implant surgery.

PMID- 9563342
TI  - Current implant biomechanical concepts and controversies.

PMID- 9563343
TI  - Three cases of methemoglobinemia associated with dental anesthesia.

PMID- 9563344
TI  - Managed care--understanding the concept.

PMID- 9563345
TI  - Compassionate assistance.

PMID- 9563346
TI  - Managed care.

PMID- 9563347
TI  - Evolution of temporomandibular joint arthroscopy. "Current status".

PMID- 9563348
TI  - A reply to a reply.

PMID- 9563349
TI  - For better or worse?

PMID- 9563350
TI  - Rapid palatal expansion: Part 1. Mineralization pattern of the midpalatal suture
      in cats.
AB  - The mineralization pattern of the midpalatal suture after rapid palatal expansion
      was investigated in 10 treated and 2 control cats, in light of the tendency of
      RPE to relapse. The rapid palatal expansion treatment consisted of active (25
      days), retention (60 days), and relapse (60 days) phases. Standardized occlusal
      radiographs were taken periodically and analyzed for suture width, suture optical
      density in anterior vs. posterior regions, and suture area measurements of
      radiopaque vs. radiolucent zones. Nine cats exhibited suture splitting. During
      the active phase, the radiolucent zone (nonmineralized tissue) increased 12-fold
      and the increase in optical density was 50% greater in the anterior over the
      posterior suture region, demonstrating increased formation of loose connective
      tissue at the anterior region. During the retention period, the suture's
      radiopaque zone (mineralized tissue) increased by 62%, the radiolucent zone
      declined (64%) and the suture width decreased (65%) indicating reorganization of
      mineralized tissue. The decrease in optical density (increased mineralization)
      was 2.5 times greater in the posterior over the anterior suture region,
      indicating that the remineralization (closure) pattern of the expanded suture is
      analogous to a zipper closed in a posteroanterior direction. During the relapse
      phase, the reduction in total suture area (41%) and in the radiopaque zone (32%)
      indicates medial convergence of the maxillary horizontal processes. From our
      findings we extrapolated that the retention of the suture anterior region should
      be longer than the posterior region to catch up the lag in rebuilding and
      maturation of the newly deposited hard tissue.

PMID- 9563351
TI  - Pain-free and mobility-free orthodontics?
AB  - Pain-free and mobility-free orthodontics are not discussed often, although they
      obviously would be significant advances and very desirable practice-builders.
      These advantages have occasionally been reported in the orthodontic literature by
      different authors who used magnetic force fields for molar distalization, aiding
      tooth eruption, etc., and are presented here in Group I. Group II discusses
      several different possible mechanisms of action, including among others, an
      accelerated osteogenic rate and a sensory neuron action potential blockade. All
      the available evidence seems to confirm that pain-free and mobility-free
      orthodontics is a real phenomenon.

PMID- 9563352
TI  - A new self-curing resin-modified glass-ionomer cement for the direct bonding of
      orthodontic brackets in vivo.
AB  - A new self-curing (chemically cured) resin-modified glass-ionomer cement, Fuji
      Ortho (GC International), is based on the technology of hybrid glass-ionomer
      restorative materials and features chemical adhesion to tooth structure and long
      term fluoride release. This article describes a 12-month clinical evaluation of
      Fuji Ortho for the direct bonding of orthodontic (metal) brackets with System 1+
      (Ormco Corp.) as a control. Three failures of Fuji Ortho occurred from a sample
      of 60 (5%), with five failures of the composite resin from a sample of 60 (8.3%).
      No statistical significance was seen between these results. Fuji Ortho is a
      satisfactory adhesive for the direct bonding of orthodontic brackets where there
      are no occlusal interferences.

PMID- 9563353
TI  - On bracket slot height: a methodologic study.
AB  - Effective bracket slot height is estimated by using a formula that describes the
      relationship between bracket slot height, wire dimensions, wire edge bevel, and
      torsional play (third-order clearance). With a torque measuring instrument, the
      torsional play was estimated for 10 different brackets (0.018-inch stated slot)
      of the same manufacturer and type. One arch wire with known dimensions and edge
      bevel was used for all the measurements. With known torsional play, wire
      dimensions and edge bevel, the bracket slot height could be calculated. This was
      performed five times for each bracket and the method error for estimation of
      torsional play for a single measurement was 0.04 degrees, corresponding to 0.36
      mm in slot height. The brackets tested had a mean slot height of 0.476 +/- 0.003
      mm, with a range of 0.470 to 0.481 mm (0.0187 +/- 0.0001 inches, range 0.0185 to
      0.0189). The variation in bracket slot height was much greater than the method
      error. The method used to measure bracket slot height seems to have a high degree
      of accuracy and is easier to implement than conventional methods.

PMID- 9563354
TI  - A new method for analyzing change in dental arch form.
AB  - Our method was developed and subsequently computerized in a system incorporating
      graphics and quantitative indexes to analyze change in dental arch form as a
      result of orthodontic treatment and subsequent relapse. The cubic spline function
      was used to model the form of the dental arches. On the basis of digitized data,
      splines were fitted to the dental arches before treatment, immediately after
      treatment, and at least 2 years after removal of retention. The fit of each
      spline was evaluated through the use of a set of normals to the curve and their
      average length. The change in form between the registrations was computed, and
      superimposed graphics of the three records were produced to visually indicate the
      magnitude of the changes in addition to numeric indexes that reflected the
      changes. Interjudge and intrajudge reliability were examined and found to be
      within acceptable limits.

PMID- 9563355
TI  - Effects of saliva and water contamination on the enamel shear bond strength of a
      light-cured glass ionomer cement.
AB  - The purpose of this study was to evaluate the shear bond strengths of Fuji Ortho
      LC (GC Corp., Tokyo, Japan), a light-cured resin-reinforced glass ionomer, used
      for direct bonding of stainless steel and ceramic brackets under four different
      enamel surface conditions: (A) nonconditioned and dry, (B) conditioned with
      polyacrylic acid and moistened with saliva, (C) conditioned with polyacrylic acid
      and moistened with water, (D) nonconditioned and wet. Stainless steel lingual
      buttons and two types of polycrystalline ceramic brackets, with either
      mechanically or chemically retentive bracket bases, were evaluated. The brackets
      were bonded to 120 freshly extracted bovine incisors; after storage in tap water
      at room temperature for 24 hours, they were subsequently tested in a shear mode
      with a universal testing machine. The maximum bond strength and the site of bond
      failure were recorded. With stainless steel brackets, subgroup B produced the
      highest bond strength (23.8 MPa), which was significantly (p < 0.05) higher than
      all the other enamel conditions tested. With ceramic brackets, the highest bond
      strengths (20.9 MPa and 25.4 MPa, respectively) were measured with subgroup C.
      Bond failure analysis revealed that each bracket type failed predominantly at the
      enamel-adhesive interface, except for Transcend 6000. The results indicate that
      the shear bond strength of Fuji Ortho LC is significantly enhanced by
      contaminating the enamel surface with either saliva or water after conditioning,
      depending on bracket type used. Even water contamination of nonconditioned enamel
      surfaces does not seem to preclude clinically acceptable bond strengths of both
      stainless steel and ceramic brackets, allowing, at the same time, a safe
      debonding without enamel damage.

PMID- 9563356
TI  - Equity and orthodontic treatment: a study among adolescents in Northern Ireland.
AB  - This epidemiological study investigated the reasons why children in Northern
      Ireland who need orthodontic treatment do not receive treatment even when it is
      provided free by the state. A total of 1584 15- and 16-year-olds were examined in
      23 high schools with the Index of Orthodontic Treatment Need. The characteristics
      of the adolescents who had received orthodontic treatment were compared with
      those who had a definite need for treatment and yet did not receive treatment or
      advice. One in 10 of the adolescents examined had an unmet need for orthodontic
      treatment. Logistic regression analysis was used to assess the influence of 11
      variables including socioeconomic status, religion, and standard of dental health
      on the uptake of orthodontic care. This analysis revealed that the only
      significant predictors of whether an adolescent received orthodontic treatment
      was the dental attendance pattern of the adolescent, the adolescent's dental
      health, and the dental attendance pattern of the adolescent's mother. Those
      adolescents who had good dental health, who regularly attended a dentist, and
      whose mother regularly attended a dentist were more likely to receive orthodontic
      treatment.

PMID- 9563357
TI  - Eruption of the permanent upper canine: a radiologic study.
AB  - The early detection of eruptive anomalies of the upper canine requires an
      understanding of its normal eruptive pattern. We studied this pattern in terms of
      upper canine inclination and its relation to the lateral incisor, on the basis of
      the panoramic radiographic records of 305 children aged 4 to 12 years. The study
      sample comprised 554 maxillary canines in the oral pre-emergence phase of
      eruption. Subject age, sex, inclination of the canine (CI), its relation to the
      lateral incisor (RCLI), and development of the lateral incisor (DLI) were
      evaluated. The results show that the canine erupts, increasing its inclination
      mesially until a maximum is reached, at about 9 years of age, after which the
      tooth begins to progressively upright itself. The individual variability of the
      degree of CI at a given age is considerable. In the initial stages, the RCLI is
      most commonly characterized by overlapping, a situation rarely seen in the final
      stages. The DLI effectively discriminates both periods, because when DLI is
      incomplete, more than half of the cases have an overlapping RCLI. In contrast,
      when the DLI is complete, this overlapping is seen in only 7% to 11% of the
      cases. This variable therefore increases the capacity to detect a possible
      eruptive anomaly at an early stage. In patients with complete DLI and overlapping
      RCLI, particularly when associated with other clinical signs such as the
      nonpalpation of the cuspid bulge in the alveolar process, the presence of dental
      agenesis, ankylosis, malformations, or ectopic eruptions, extraction of the
      primary canine is advised to prevent impaction.

PMID- 9563358
TI  - Rectangular wire and third-order torque: a new perspective.
AB  - The Differential Straight Arch technique, more commonly known as "Tip-Edge" (TP
      Orthodontics Inc.), uses a modified edgewise type bracket to allow differential
      tooth movement. As bracketed teeth incline toward their finishing positions, the
      geometry of the arch wire slot causes the vertical slot dimension available to
      the arch wire to increase. Advantage has been taken of this facility, to evolve
      an entirely new torquing system for final finishing, during the root correction
      phase. Instead of increasing rectangular arch wire size to fit the arch wire
      slot, as with conventional edgewise brackets, the Tip-Edge method reduces the
      vertical arch wire slot dimension to achieve a precise, three-dimensional
      relationship to a full-sized rectangular arch wire. The active component is
      provided by auxiliary springs. The method, which awaits mathematical analysis, is
      described and illustrated with two case reports.

PMID- 9563359
TI  - Extraction treatment of a Class II, Division 1 malocclusion with anterior open
      bite with headgear and vertical elastics.

PMID- 9563360
TI  - Condylar growth and glenoid fossa displacement during childhood and adolescence.
AB  - This study evaluated age and gender differences in the growth of the mandibular
      condyle and displacement of the glenoid fossa. The results pertain to
      longitudinal samples of untreated French Canadians, including 118 children and
      155 adolescents. Childhood and adolescent growth were described for girls aged
      between 6 and 10 years and 9 and 13 years, respectively, and for boys aged
      between 8 and 12 years and 11 and 15 years, respectively. Four-year growth
      changes of the cephalometric landmarks condylion and articulare were evaluated.
      Mandibular and cranial/cranial base structural superimpositions were used to
      assess condylar growth and fossa displacement, respectively. The results showed
      that the condyle grew between 0.8 and 1.3 mm posteriorly and between 9.0 and 10.7
      mm superiorly over the 4-year periods; the articulare landmark showed
      significantly more posterior and less superior growth than the condylion
      landmark. Relative to the cranial base reference structures, the fossa was
      displaced between 1.8 and 2.1 mm posteriorly and between 1.0 and 1.8 mm
      inferiorly. The articulare showed significantly more inferior movement than the
      condylion. Boys showed significantly greater superior condylar growth during
      adolescence than during childhood. The glenoid fossa demonstrated greater
      posterior and inferior displacement during adolescence than during childhood.

PMID- 9563361
TI  - Alveolar and skeletal dimensions associated with overbite.
AB  - The aim of this study was to investigate whether in the maxilla and in the
      mandible the structure of the anterior medial sagittal alveolar and basal bone is
      related to the overbite. A total of 460 untreated adult subjects were divided
      into four groups with either deep bite, normal overbite, end-to-end bite, or open
      bite and were compared. The overbite, lower face height, and anterior alveolar
      and basal midsagittal cross-sectional areas from the maxilla and the mandible
      were assessed on lateral cephalometric radiographs. An index was calculated,
      dividing the sagittal by the vertical dimension of the midsagittal cross
      sectional area. A deeper bite coincided with smaller lower face height, larger
      alveolar and basal areas, and a more widened shape of the symphysis. If the lower
      face height was introduced as a covariable, the open bite group showed
      significantly smaller maxillary and mandibular alveolar and basal cross-sectional
      areas compared with the end-to-end group, the normal overbite group, or the deep
      bite group. Vertical variation of the overbite probably coincides with a relative
      hyperdevelopment or hypodevelopment of the symphysis.

PMID- 9563362
TI  - Profile changes in patients with class III malocclusions after Delaire mask
      therapy.
AB  - The purpose of this study was to make a detailed evaluation of hard and soft
      tissue changes after Delaire orthopedic mask therapy (France-Orthodontie). The
      treatment group, which comprised 16 girls (mean age: 8.65 years, SD: 1.4 years)
      with skeletal Class III relationships caused by maxillary retrognathism, was
      compared with an untreated control group of 10 girls (mean age: 9.29 years, SD:
      1.4 years). The following results were obtained: (1) After maxillary protraction,
      the maxilla was displaced anteriorly, whereas the mandible rotated posteriorly;
      (2) the maxillary incisors moved in the anterior direction, whereas the
      mandibular incisors moved posteriorly; (3) the mandibular plane angle and
      anterior lower and total face heights increased; (4) these changes were reflected
      in the profile, whereby the skeletal profile convexity increased and soft tissue
      facial angle and facial convexity decreased; and (5) the Class III concave
      profile became more balanced, with the upper lip area becoming more marked.

PMID- 9563363
TI  - Reliability of three methods of occlusion classification.
AB  - Four orthodontic faculty at one dental school classified 25 dental casts
      according to the classification systems of Angle, Katz, and the British Incisor
      Classification. The dental casts were selected from a pool of 350 pretreatment
      graduate orthodontic cases and were those deemed the most atypical. The results
      demonstrated that Katz's classification was more reliable than both Angle and the
      British. Angle's classification was the least reliable of the three methods.

PMID- 9563364
TI  - Orthodontics--a vanishing profession?

PMID- 9563365
TI  - Off-the-shelf digital imaging/prediction.

PMID- 9563366
TI  - Litigation, legislation, and ethics. The problem, electronic data transmission
      and the law.

PMID- 9563367
TI  - Current issues for establishing inhaled corticosteroids as the antiinflammatory
      agents of choice in asthma.
AB  - Airway inflammation appears to be present even in the mildest of asthma, and
      inhaled corticosteroids now form the mainstay of asthma therapy. Inhaled
      corticosteroids largely avoid the adverse effects associated with oral steroids
      and are now recommended in newly detected disease. Inhaled corticosteroids reduce
      airway inflammation, airway hyperresponsiveness, and the symptoms of asthma and
      improve lung function, irrespective of the patient's age or asthma severity.
      Several different inhaled corticosteroids are available as therapeutic options
      for the treatment of asthma, and these include fluticasone propionate,
      beclomethasone dipropionate, and budesonide. The efficacy and safety of inhaled
      corticosteroids are compared in this article, and inhaled corticosteroid therapy
      is also compared with other therapies. Recently, there has been a consensus that
      the optimal use of inhaled corticosteroids for asthma management is using a
      "start high--go low" approach, and the reasons for this are discussed.

PMID- 9563368
TI  - Development of fluticasone propionate and comparison with other inhaled
      corticosteroids.
AB  - Fluticasone propionate (FP) is a trifluorinated glucocorticoid based on the
      androstane nucleus. It was selected for development from structure-activity
      relationships (topical anti-inflammatory, cutaneous vasoconstriction, and
      hypothalamic-pituitary-adrenal axis suppression) of a series of 17beta
      carbothioates. FP is 3-, 300-, and 1000-fold more lipophilic than beclomethasone
      dipropionate, budesonide, and triamcinolone acetonide, respectively. FP has an
      absolute affinity (KD) for the glucocorticoid receptor of 0.5 nmol/L and a
      relative receptor affinity 1.5-fold higher than beclomethasone-17-monopropionate
      (17-BMP) and mometasone furoate, 3-fold higher than budesonide, and 20-fold
      higher than flunisolide and triamcinolone acetonide. The rate of association of
      FP with the receptor is faster and the rate of dissociation slower than other
      corticosteroids. The resulting half-life of the FP active steroid-receptor
      complex is >10 hours, compared with approximately 5, 7.5, and 4 hours for
      budesonide, 17-BMP, and triamcinolone acetonide, respectively. FP has high
      selectivity for the glucocorticoid receptor, with little or no activity at other
      steroid receptors. FP is more potent than beclomethasone dipropionate,
      budesonide, triamcinolone acetonide, and mometasone furoate in inhibiting human T
      cell migration and proliferation, inhibiting CD4+ T-cell cytokine and basophil
      histamine release, attenuating adhesion molecule expression, stimulating
      inflammatory cell apoptosis, and inducing cellular antiprotease release. In
      asthma patients, FP decreases the number of CD3+, CD4+, CD8+, and CD25+ T cells,
      mast cells, and eosinophils in bronchial biopsies, in addition to suppressing
      CD1a-dendritic and IgE+ cells and HLA-DR. FP, therefore, has a good pharmacologic
      profile for a topical steroid with increased intrinsic glucocorticoid potency and
      potent anti-inflammatory activity.

PMID- 9563369
TI  - Pharmacokinetics and pharmacodynamics of inhaled corticosteroids.
AB  - There are significant differences in the pharmacokinetic properties of inhaled
      corticosteroids currently used in medical practice. All are rapidly cleared from
      the body but they show varying levels of oral bioavailability and more
      importantly variation in the rate of absorption after inhalation. Oral
      bioavailability is lowest for fluticasone propionate, indicating a low potential
      for unwanted systemic corticosteroid effects. Mathematical modeling has shown
      pulmonary residence times to be longest for fluticasone propionate and
      triamcinolone acetonide but shortest for budesonide and flunisolide. These
      properties appear to relate to pulmonary solubility, which appears to be the rate
      limiting step in the absorption process.

PMID- 9563370
TI  - Clinical relevance of inhaled corticosteroids and HPA axis suppression.
AB  - Although hypothalamic-pituitary-adrenal (HPA) axis suppression has traditionally
      been viewed as an adverse event after long-term administration of
      corticosteroids, this effect can also be used to compare the potency of different
      inhaled corticosteroids. However, various factors such as the dose, frequency of
      administration, treatment duration, study population (patients with asthma versus
      normal volunteers), and prior systemic steroid therapy influence adrenal
      suppression with inhaled corticosteroids. The different adrenal function tests
      available and the results produced with these tests also must be considered along
      with the clinical relevance of such results. Whereas low doses of inhaled
      corticosteroids are likely to cause minimal or no HPA axis suppression, long-term
      high-dose inhaled corticosteroid use may result in significant suppression by
      effectively replacing endogenous steroid production. The risk of acute adrenal
      insufficiency in patients taking low/medium-dose inhaled corticosteroids is
      minimal, but patients receiving long-term high-dose treatment may require
      supplementary systemic steroids during stress challenges, especially if they have
      previously received long-term systemic steroid treatment.

PMID- 9563371
TI  - Effects of inhaled corticosteroids on growth.
AB  - Inhaled corticosteroids are an established treatment for asthma in childhood. The
      risk of adverse events associated with conventional doses of inhaled
      corticosteroids is low, but in children with asthma concern remains about the
      potential effects of these compounds on growth. Short-term growth in children can
      be measured with knemometry. This technique measures changes in lower leg length
      that can be detected over periods as short as days or even intradaily. However,
      nonlinearity of lower leg growth and the complexity of statural growth confound
      any attempts to derive a predicted height from short-term measurements of the
      lower leg. Knemometry is better at detecting growth suppression than growth
      promotion. With knemometry, inhaled fluticasone propionate 200 microg/day had no
      effect on lower leg growth, but beclomethasone propionate 400 microg/day
      significantly reduced lower leg growth. Inhaled budesonide also caused a dose
      dependent reduction in lower leg growth, but this only reached significance at
      the 800 microg/day dose. Long-term growth in children is measured with
      stadiometry. Growth velocity can only be determined from measurements of height
      taken over a period of at least 1 year. There is no evidence that inhaled
      corticosteroids at conventional doses have an adverse effect on the final height
      of children, but it is important to be aware of the growth-impairing effect of
      poorly controlled asthma. All children with asthma receiving inhaled
      corticosteroids should have their growth monitored, and any deviation from the
      expected pattern should be investigated. The effect of early intervention with
      inhaled steroids in childhood warrants further investigation.

PMID- 9563372
TI  - Effects of inhaled corticosteroids on bone density and metabolism.
AB  - Oral corticosteroids have adverse effects on bone density and metabolism. With
      the increased use of inhaled corticosteroids together with the use of higher
      doses for the treatment of asthma, the long-term effects of inhaled
      corticosteroids on bone metabolism and density must be evaluated. This article
      discusses the markers of bone resorption and formation together with techniques
      used to measure cortical and trabecular bone density. The effects of inhaled
      corticosteroids on bone density and metabolism as determined by these techniques
      are described in detail. Overall, inhaled corticosteroids are extremely safe,
      even at high doses, with the long-term risk of bone loss being extremely small
      compared with oral corticosteroids. In particular, fluticasone propionate at the
      recommended doses appears to be free of effects on bone density and metabolism.
      Finally, the use of inhaled corticosteroids results in the control of asthma,
      allowing patients to exercise, which itself improves bone density and protects
      against osteoporosis.

PMID- 9563374
TI  - Wrong-site surgery.

PMID- 9563375
TI  - Neer hemiarthroplasty and Neer total shoulder arthroplasty in patients fifty
      years old or less. Long-term results.
AB  - Seventy-eight Neer hemiarthroplasties and thirty-six Neer total shoulder
      arthroplasties were performed at our institution, between January 1, 1976, and
      December 31, 1985, in ninety-eight patients who were fifty years old or less. Two
      patients (two shoulders) died, and four patients (four shoulders) were lost to
      follow-up. The remaining seventy-four hemiarthroplasties (95 per cent) in sixty
      four patients and thirty-four total shoulder arthroplasties (94 per cent) in
      thirty-one patients were included in the clinical analysis as the preoperative
      and operative records were complete and the patients had been followed for at
      least five years (mean, 12.3 years) or until revision. All 114 shoulders were
      included in the survivorship analysis. Both total shoulder arthroplasty and
      hemiarthroplasty resulted in significant long-term relief of pain (p < 0.0001) as
      well as improvement in active abduction (p < 0.0001) and external rotation (p <
      0.0001). However, with the numbers available, we could not detect a significant
      difference between the two procedures with respect to these variables. A complete
      set of radiographs was available for sixty-eight (92 per cent) of the seventy
      four shoulders that had a hemiarthroplasty and for thirty-two (94 per cent) of
      the thirty-four shoulders that had a total shoulder arthroplasty. A radiolucent
      line around the humeral component was noted after sixteen (24 per cent) of the
      hemiarthroplasties and after seventeen (53 per cent) of the total shoulder
      arthroplasties. A radiolucent line around the glenoid component was seen after
      nineteen (59 per cent) of the total shoulder arthroplasties. Erosion of the
      glenoid was found after forty-six (68 per cent) of the hemiarthroplasties. The
      results were graded according to a modification of the system of Neer et al. and
      of Cofield. Fifteen hemiarthroplasties led to an excellent result; twenty-four, a
      satisfactory result; and thirty-five, an unsatisfactory or unsuccessful result.
      Four total shoulder arthroplasties were followed by an excellent result;
      thirteen, a satisfactory result; and seventeen, an unsatisfactory or unsuccessful
      result. The estimated survival of the hemiarthroplasty prostheses (with 95 per
      cent confidence intervals) was 92 per cent (86 to 98 per cent) at five years, 83
      per cent (75 to 93 per cent) at ten years, and 73 per cent (59 to 88 per cent) at
      fifteen years. Analysis of the results in association with the two major
      diagnoses revealed that the risk of revision was higher for the thirty shoulders
      that had the hemiarthroplasty for the treatment of the sequelae of trauma than
      for the twenty-eight that had the procedure for the treatment of rheumatoid
      arthritis (p = 0.017). The estimated survival of the total shoulder prostheses
      (with 95 per cent confidence intervals) was 97 per cent (92 to 100 per cent) at
      five years, 97 per cent (91 to 100 per cent) at ten years, and 84 per cent (70 to
      100 per cent) at fifteen years. The risk of revision was higher for the seven
      shoulders that had had a tear of the rotator cuff at the time of the operation
      than for the twenty-seven that had not had one (p = 0.029). The data from the
      present study indicate that a shoulder arthroplasty provides marked long-term
      relief of pain and improvement in motion; however, nearly half of all young
      patients who have a shoulder arthroplasty have an unsatisfactory result according
      to a rating system. Care should be exercised when either a hemiarthroplasty or a
      total shoulder arthroplasty is offered to patients who are fifty years old or
      less.

PMID- 9563373
TI  - Relative safety and efficacy of inhaled corticosteroids.
AB  - Inhaled corticosteroids are the main treatment for controlling asthma in adults
      and children. However, there is still some concern over the safety of these drugs
      when used at high doses and for long periods of time. Hence issues relating to
      the efficacy and safety of inhaled corticosteroids have been extensively
      researched over the past 5 years. General considerations, such as use of an
      appropriate dose of inhaled corticosteroid in an appropriate asthma population,
      are discussed. Studies comparing the efficacy and safety of fluticasone
      propionate, beclomethasone dipropionate, and budesonide are highlighted, and a
      systematic review of these studies suggests that fluticasone propionate has a
      better efficacy:safety therapeutic ratio than either beclomethasone dipropionate
      or budesonide.

PMID- 9563376
TI  - A dynamic analysis of glenohumeral motion after simulated capsulolabral injury. A
      cadaver model.
AB  - We used a dynamic shoulder-testing apparatus and nine fresh-frozen, entire upper
      extremities from cadavera to evaluate the effects of varying degrees of
      capsulolabral injury on the kinematics of the glenohumeral joint during abduction
      in the scapular plane and external rotation. Joint kinematics were recorded with
      use of a six-degrees-of-freedom magnetic tracking device before and after the
      creation of each capsulolabral lesion in a progressive manner. Dislocation did
      not occur after simulation of a large Bankart lesion or even after sectioning of
      the anterior aspect of the joint capsule. However, division of the entire joint
      capsule (that is, both the anterior aspect and the posterior aspect) resulted in
      a significant increase (p < 0.05) in posterior translation during abduction in
      the scapular plane, and two of the nine shoulders dislocated posteriorly.
      External rotation of the abducted extremity produced no increase in anterior or
      posterior translation.

PMID- 9563377
TI  - Infection after total elbow arthroplasty.
AB  - The purpose of this study was to review our experience with the treatment of
      twenty-five infections (in twenty-five patients) after total elbow arthroplasty
      and to examine indications for salvage of the prosthesis compared with those for
      resection arthroplasty. The patients were divided into three groups on the basis
      of treatment. Group I comprised fourteen patients who were managed with multiple,
      extensive irrigation and debridement procedures with retention of the original
      components. The primary indication for retention of the prosthesis was evidence
      that it was well fixed as determined both radiographically and intraoperatively.
      Group II comprised six patients who had removal of the prosthesis and debridement
      followed by immediate or staged reimplantation. Group III comprised five patients
      who were managed with resection arthroplasty. The infection was successfully
      eradicated in seven of the fourteen elbows that had salvage of the prosthesis
      with irrigation and debridement. The results were strongly dependent on the
      causative organism; attempts at debridement failed in the four elbows that were
      infected with Staphylococcus epidermidis compared with three of the ten that were
      infected with another organism. Four of the six patients in Group II had
      successful reimplantation of a prosthesis; in three, the infection had been
      caused by an organism other than Staphylococcus epidermidis. Only one of the
      three patients who had a Staphylococcus epidermidis infection had a successful
      reimplantation. None of the five patients who had a resection arthroplasty had
      signs of infection at the latest follow-up examination. We concluded that salvage
      of the prosthesis with extensive irrigation and debridement in the presence of an
      infection about the elbow can be reasonably successful if the infecting organism
      is not Staphylococcus epidermidis and if the components are well fixed. When
      removal of the components is warranted, staged reimplantation can also be highly
      successful when the infecting organism is not Staphylococcus epidermidis.
      However, the repeated operations necessary to retain a prosthesis and the high
      rates of complications seen with this approach--and the relatively good rates of
      satisfaction obtained with resection arthroplasty--suggest that resection
      arthroplasty remains the procedure of choice in medically frail patients or in
      patients for whom function of the elbow is less of a concern.

PMID- 9563378
TI  - Changes in interstitial pressure and cross-sectional area of the cubital tunnel
      and of the ulnar nerve with flexion of the elbow. An experimental study in human
      cadavera.
AB  - The purpose of this study was to determine the relationship between the ulnar
      nerve and the cubital tunnel during flexion of the elbow with use of magnetic
      resonance imaging and measurements of intraneural and extraneural interstitial
      pressure. Twenty specimens from human cadavera were studied with the elbow in
      positions of incremental flexion. With use of magnetic resonance imaging, cross
      sectional images were made at each of three anatomical regions of the cubital
      tunnel: the medial epicondyle, deep to the cubital tunnel aponeurosis, and deep
      to the flexor carpi ulnaris muscle. The cross-sectional areas of the cubital
      tunnel and the ulnar nerve were calculated and compared for different positions
      of elbow flexion. Interstitial pressures were measured with use of
      ultrasonographic imaging to allow a minimally invasive method of placement of the
      pressure catheter, both within the cubital tunnel and four centimeters proximal
      to it, at 10-degree increments from 0 to 130 degrees of elbow flexion. As the
      elbow was moved from full extension to 135 degrees of flexion, the mean cross
      sectional area of the three regions of the cubital tunnel decreased by 30, 39,
      and 41 per cent and the mean area of the ulnar nerve decreased by 33, 50, and 34
      per cent. These changes were significant in all three regions of the cubital
      tunnel (p < 0.05). The greatest changes occurred in the region beneath the
      aponeurosis of the cubital tunnel with the elbow at 135 degrees of flexion. The
      mean intraneural pressure within the cubital tunnel was significantly higher than
      the mean extraneural pressure when the elbow was flexed 90, 100, 110, and 130
      degrees (p < 0.05). With the elbow flexed 130 degrees, the mean intraneural
      pressure was 45 per cent higher than the mean extraneural pressure (p < 0.001).
      Similarly, with the elbow flexed 120 degrees or more, the mean intraneural
      pressure four centimeters proximal to the cubital tunnel was significantly higher
      than the mean extraneural pressure (p < 0.01). Relative to their lowest values,
      intraneural pressure increased at smaller angles of flexion than did extraneural
      pressure, both within the cubital tunnel and proximal to it. With the numbers
      available, we could not detect any significant difference in intraneural pressure
      measured, either at the level of the cubital tunnel or four centimeters proximal
      to it, after release of the aponeurotic roof of the cubital tunnel.

PMID- 9563379
TI  - Salvage of a recurrently dislocating total hip prosthesis with use of a
      constrained acetabular component. A retrospective analysis of fifty-six cases.
AB  - Fifty-six constrained acetabular components were placed, between April 1988 and
      February 1993, in fifty-five patients who had had recurrent dislocations
      (average, six dislocations; range, two to twenty dislocations) of the femoral
      component after a previous total hip arthroplasty. All patients had additional
      factors contributing to the instability of the implant, including absence or
      disruption of the abductor mechanism, poor health, mental retardation, confusion,
      and Alzheimer disease. One patient was lost to follow-up. The remaining patients
      were followed clinically for a minimum of three years (average, sixty-four
      months; range, thirty-seven to ninety-seven months) or until the time of death.
      During the follow-up interval, only two (4 per cent) of the fifty-five patients
      had a subsequent dislocation. The use of this type of component should be
      considered for patients who have recurrent dislocation if other treatment
      modalities are unlikely to be effective.

PMID- 9563380
TI  - Treatment of high dislocation of the hip in adults with total hip arthroplasty.
      Operative technique and long-term clinical results.
AB  - The clinical results of eighty-four total hip arthroplasties performed through a
      transtrochanteric approach in sixty-seven patients who had a high dislocation of
      the hip (the femoral head completely out of the acetabulum), from 1976 to 1994,
      were reviewed. The acetabular component was placed in the true acetabulum and the
      femur was shortened at the level of the femoral neck, along with release of the
      psoas tendon and the small external rotators, in order to facilitate reduction of
      the components and to avoid neurovascular complications. Eleven hip prostheses
      (13 per cent) failed at a mean of 6.4 years (range, two months to sixteen years)
      postoperatively; the failure was due to aseptic loosening of both components in
      four hips, aseptic loosening of the stem only in three, late infection in three,
      and malpositioning of the acetabular component that caused recurrent dislocations
      in one. The other seventy-three hips were functioning well at the latest follow
      up examination, two to twenty years (mean, 7.1 years) postoperatively. The
      overall cumulative rate of success was 92.4 per cent (95 per cent confidence
      interval, 89.5 to 95.3 per cent) at five years and 88.0 per cent (95 per cent
      confidence interval, 82.2 to 93.8 per cent) at ten years. We believe that this
      operative technique of total hip arthroplasty is effective for the treatment of
      the difficult condition of high dislocation of the hip.

PMID- 9563381
TI  - Porous-coated metal-backed patellar components in total knee replacement. A
      postmortem retrieval analysis.
AB  - The use of porous-coated metal-backed patellar components to achieve consistent
      fixation by bone ingrowth and to provide relief of pain warrants serious
      scrutiny. We conducted a quantitative postmortem investigation of eleven
      consecutively retrieved components with use of high-resolution contact
      radiographs, electron microscopy, and histological analysis. The implants had
      been in situ for a mean (and standard deviation) of 45+/-36 months (range, one to
      eighty-four months). Analysis of the high-resolution contact radiographs revealed
      that a mean of 86+/-12 per cent (range, 61 to 100 per cent) of the porous coating
      was in contact with the host bone. Backscattered electron imaging showed that the
      mean volume fraction of bone ingrowth was 13+/-9 per cent (range, 0 to 30 per
      cent). No significant difference was detected, with the numbers available,
      between the volume fraction of the bone ingrowth measured in the porous coating
      and that of the host cancellous bone in the patellae.

PMID- 9563383
TI  - Intraoperative monitoring with stimulus-evoked electromyography during placement
      of iliosacral screws. An initial clinical study.
AB  - A consecutive series of twenty-seven patients who had thirty acute unstable (type
      C) fractures of the pelvic ring was studied prospectively to evaluate the use of
      stimulus-evoked electromyography to decrease the risk of iatrogenic nerve-root
      injury during the insertion of iliosacral screws. A prerequisite for inclusion in
      the study was a normal neurological status preoperatively; somatosensory evoked
      potentials were monitored to further document the neurological status both before
      and after insertion of the screw or screws. A total of fifty-one iliosacral
      screws were inserted, and a current threshold of more than eight milliamperes was
      selected as the level that indicated that the drill-bit was a safe distance from
      the nerve root. Four of the fifty-one screws were redirected because of
      information obtained with stimulus-evoked electromyography. Postoperatively, all
      patients had a normal neurological status. Computerized tomography, although not
      accurate for detailed measurements, demonstrated that all of the screws were in a
      safe, intraosseous position. Monitoring with stimulus-evoked electromyography
      appears to provide reliable data and may decrease the risk of iatrogenic injury
      to the nerve roots during operations on the pelvic ring.

PMID- 9563382
TI  - Atraumatic osteonecrosis of the talus.
AB  - Thirty-seven ankles in twenty-four patients were treated at our institution
      between July 1, 1974, and December 31, 1996, for atraumatic osteonecrosis of the
      talus. This group represents 2 per cent of the 1056 patients who were managed for
      osteonecrosis during this period. There were twenty-one women and three men, and
      their mean age was forty years (range, twenty-six to sixty-two years) at the time
      of the diagnosis. Thirteen (54 per cent) of the twenty-four patients had
      bilateral involvement. Sixteen patients (67 per cent) had a disease that affects
      the immune system, including systemic lupus erythematosus (thirteen patients),
      scleroderma (one), insulin-dependent diabetes mellitus (one), and multiple
      sclerosis (one). Four patients had a history of regular alcohol use, and four
      patients had a history of moderate smoking. One patient had a protein-S
      deficiency, one patient had had a renal transplant, and one patient had a history
      of asthma. Two patients had no identifiable risk factors for osteonecrosis
      [corrected]. Fifteen patients (63 per cent) had involvement of other large
      joints. The mean duration of symptoms before the patients were seen was 5.4
      months (range, two months to two years). The mean ankle score at the time of
      presentation was 34 points (range, 2 to 75 points), according to the system of
      Mazur et al. A radiographic review revealed that, according to the system of
      Ficat and Arlet, eight ankles had stage-III or IV disease of the talus at
      presentation. The remaining twenty-nine ankles had stage-II disease. The
      osteonecrosis was seen in the posterolateral aspect of the talar dome (zones III
      and IV on the sagittal images and zones II, III, and IV on the coronal images) in
      twenty-two of the twenty-three ankles for which magnetic resonance images were
      available. The osteonecrosis was seen in the anteromedial aspect of the talar
      dome (zones I and II on the sagittal images and zone I on the coronal images) in
      the remaining ankle. Bone scans, which were available for eleven ankles, revealed
      increased uptake in the talus. All patients were initially managed non
      operatively with restricted weight-bearing, an ankle-foot orthosis, and use of
      analgesics; two ankles responded to this regimen. Thirty-two ankles that remained
      severely symptomatic were treated with core decompression, which was useful in
      the treatment of precollapse (stage-II) disease. Twenty-nine of these ankles had
      a fair-to-excellent clinical outcome a mean of seven years (range, two to fifteen
      years) postoperatively; the remaining three ankles had an arthrodesis after the
      core decompression failed. Three ankles were treated initially with an
      arthrodesis for postcollapse (stage-III or IV) disease. All six of the ankles
      that had an arthrodesis fused, at a mean of seven months (range, five to nine
      months) postoperatively. When patients who have a history of osteonecrosis are
      seen because of pain in the ankle, the diagnosis of osteonecrosis of the talus
      should be considered. Early detection may allow the ankle to be treated non
      operatively or with core decompression and thus reduce the need for arthrodesis.
      We also believe that when a patient has osteonecrosis of the talus, the hips
      should be screened with use of standard radiography or magnetic resonance
      imaging, or both.

PMID- 9563384
TI  - A comparison of hydroxyapatite-coated, titanium-coated, and uncoated tapered
      external-fixation pins. An in vivo study in sheep.
AB  - Three types of surfaces for external fixation pins were compared. One hundred and
      eight stainless-steel tapered 5/6-millimeter pins were divided into three groups:
      thirty-six pins remained uncoated (Group A), thirty-six were plasma-sprayed with
      hydroxyapatite (Group B), and thirty-six were plasma-sprayed with titanium (Group
      C). The pins were implanted in the left tibia of eighteen sheep, with each sheep
      receiving six pins from the same group. A unilateral fixator then was assembled
      on the pins. The medial aspect of the mid-part of the tibial diaphysis was
      exposed, and a five-millimeter-long cylinder of bone was removed so that load
      would be borne by the bone-pin interfaces. Six weeks after the procedure,
      radiographs demonstrated rarefaction of twenty-nine pin tracks in Group A,
      fifteen in Group B, and thirty in Group C (p = 0.021 for Group A compared with
      Group B and p = 0.016 for Group B compared with Group C). The mean final
      insertion torque (and standard deviation) was 4360+/-1050 newton-millimeters in
      Group A, 3420+/-676 newton-millimeters in Group B, and 3740+/-643 newton
      millimeters in Group C. With the numbers available, no significant differences
      could be detected among these values. The mean extraction torque was 253+/-175
      newton-millimeters in Group A, 3360+/-1260 newton-millimeters in Group B, and
      1720+/-1030 newton-millimeters in Group C (p = 0.002 for Group A compared with
      Group B, p = 0.017 for Group A compared with Group C, and p = 0.03 for Group B
      compared with Group C). The extraction torque was significantly lower than the
      corresponding insertion torque in both Group A (p < 0.001) and Group C (p =
      0.003); no significant difference could be found, with the numbers available, in
      Group B (hydroxyapatite-coated pins). At sixty times magnification, direct
      contact was seen along a mean of 16+/-9 per cent of the bone-pin interface in
      Group A, 30+/-12 per cent of the interface in Group B, and 28+/-15 per cent of
      the interface in Group C (p = 0.042 for Group A compared with Group C). However,
      at 10,000 times magnification, direct bone-pin contact was found only in Group B.

PMID- 9563385
TI  - Calcifying fibrous pseudotumor. A case report.

PMID- 9563386
TI  - Failure of a constrained acetabular prosthesis of a total hip arthroplasty. A
      report of four cases.

PMID- 9563387
TI  - Fracture-dislocation of the elbow.

PMID- 9563389
TI  - Responding to change.

PMID- 9563390
TI  - Current concepts review. Tuberculosis of bones and joints (78-A:288-298, Feb.
      1996) by Watts and Lifeso.

PMID- 9563391
TI  - Coronal shear fractures of the distal end of the humerus (78-A: 49-54, Jan.
      1996), McKee et al.

PMID- 9563392
TI  - Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg
      Perthes disease (78-A: 3-13, Jan. 1996)

PMID- 9563393
TI  - Relationship between the volume of total hip replacements performed by providers
      and the rates of postoperative complications in the state of Washington (79-A:
      485-494, April 1997), by Kreder et al.

PMID- 9563394
TI  - Relationship between the volume of total hip replacements performed by providers
      and the rates of postoperative complications in the state of Washington (79-A:485
      494, April 1997), by Kreder et al.

PMID- 9563395
TI  - Infection around joint replacements in patients who have a renal or liver
      transplantation (79-A: 36-43, Jan. 1997), Tannenbaum et al .

PMID- 9563396
TI  - Management of bleeding complications in redo cardiac operations.
AB  - Bleeding remains a complication of certain complex surgical procedures,
      particularly those cardiac operations associated with long bypass times and
      profound hypothermia. Clinical and novel experimental strategies to reduce
      bleeding and the need for blood and blood-product transfusions are the focus of
      this review. Preoperative assessment of the patient will identify drug-induced,
      acquired, or inherited coagulation defects that may contribute to this problem.
      The main attention is directed to the perioperative period, and broad areas
      discussed include the preoperative use of erythropoietin to increase red blood
      cell mass, autologous donation either preoperatively or before bypass,
      autotransfusion/hemofiltration, and acceptance of relative anemia both during the
      operation and into the postoperative period. A further, often overlooked,
      management strategy in treating major coagulopathies is the consideration of the
      cost and half-lives of the coagulation factors in individual blood components.
      Prevention of bleeding has become possible both by manipulation of the control of
      coagulation and inflammatory processes and by the introduction of pharmacologic
      agents such as aprotinin. Aprotinin is widely used and has proven efficacy in the
      management of excess bleeding. It is a serine protease inhibitor and has several
      possible mechanisms of action, including inhibition of the plasma enzyme systems
      activated by contact with the foreign surface of the bypass circuit and
      preservation of platelet function. Safety issues include the possibility of
      hypersensitivity and anaphylactic reaction on a second exposure. Concerns that
      aprotinin may induce a prothrombotic or coagulant state have no basis in theory
      or any good evidence in the current literature. A recent study specifically
      sought to identify the presence of disseminated microvascular platelet-fibrin
      thrombi present at autopsy in patients who had received aprotinin therapy. The
      study concluded that diffuse platelet-fibrin thrombi were not a direct
      complication of aprotinin therapy. Finally, modern molecular biology has led to
      the recent development of an inhibitor for factor IXa that competitively replaced
      IXa in the intrinsic complex and blocked the conversion of factor X to factor Xa.
      This compound is under investigation in animal studies. These have so far shown
      efficacy in reducing blood loss after bypass in comparison with standard heparin
      anticoagulation.

PMID- 9563398
TI  - Brain damage during cardiopulmonary bypass.
AB  - The development of systems that allow cardiopulmonary bypass have been
      responsible for the growth of our specialty. In recent years continuing reduction
      in the mortality associated with cardiac operations has reinforced our confidence
      in the reliability and safety of perfusion equipment. Cardiac surgeons are aware
      that the mortality for most cardiac surgical procedures has decreased
      dramatically and overall morbidity has been reduced significantly. However, it is
      still clear that cardiopulmonary bypass techniques are not perfect. Indeed, it is
      fair to say that the period of bypass still contributes to significant morbidity
      in most patients. In particular, cerebral injury, the focus of this review, is a
      significant problem for patients and their caregivers and for funding of health
      care systems. Incidence rates for stroke are around 2% to 3%, with increased risk
      in elderly patients and other high-risk groups. This relatively low incidence of
      what is universally recognized as a serious complication may be contrasted with
      the much higher reported incidence of cognitive defects assessed by
      neuropsychologic testing. The incidence of cognitive defects is as high as 60% at
      8 days postoperative with reduction to 25% to 30% incidence at 8 weeks and 12
      months. There are a variety of ways, at least potentially, in which the brain may
      be injured during an operation with cardiopulmonary bypass, including reduced
      cerebral blood flow, microembolism and macroembolism, and a systemic inflammatory
      response. These mechanisms interrelate and produce synergistic, cumulative
      effects on brain function during and after the operation. Reducing the incidence
      and effects of this altered brain function will rely on both preventive and
      therapeutic strategies. These, in turn, must be based on an understanding of the
      pathophysiology of these mechanisms of cerebral injury and directed toward ways
      to optimize cerebral perfusion, minimize embolic vascular occlusion, and develop
      pharmacologic approaches to modify the systemic inflammatory response.

PMID- 9563397
TI  - Aprotinin versus lysine analogues: the debate continues.
AB  - The decision to use any pharmacologic intervention inevitably rests on balancing
      the efficacy and safety of the intervention. The advent of the acquired
      immunodeficiency syndrome epidemic greatly increased awareness of transfusion
      related illnesses and focused attention on methods to prevent the need for blood
      and blood products. This has led, especially in the last decade, to increased use
      of drugs to help reduce perioperative bleeding. This chapter focuses on the
      lysine analogues and aprotinin as the serine protease inhibitor currently
      available in clinical practice. Both groups of compounds have recently shown
      promise in reducing surgical bleeding. However, the reader will notice that none
      of these agents are new; they have all been available for more than 30 years.
      What is new is their use in preventing bleeding. We therefore have considerable
      knowledge regarding the safety of these compounds. The first part of this review
      will compare the actions of these two types of agents on the processes related to
      thrombosis, hemostasis, and fibrinolysis. This is followed by a comparison of the
      efficacy of each intervention and any dose-response relationship. This section
      highlights the reported reduction in postoperative bleeding with both classes of
      agent. There is, however, no obvious or consistent reduction in the transfusion
      of blood and blood products in patients given lysine analogues. In contrast,
      there is a consistent reduction in the need for blood transfusions in patients
      given aprotinin therapy. The next major section will discuss the evidence to
      suggest that these drugs may, because of their known effects on the processes
      related to inflammation, hemostasis, and cellular repair, contribute to an
      improvement or worsening of outcome after cardiac operations. In particular, this
      section focuses on the antiinflammatory actions and modifications in vascular
      tone associated with aprotinin therapy. These effects may be related to improved
      outcome in patients by reducing the incidence of permanent neurologic deficit or
      stroke after heart operations, as well as inhibiting pulmonary vascular
      hyperreactivity and hypertension in susceptible individuals. Finally, this brief
      review discusses the safety issues that have been raised in regard to each of
      these classes of agents, specifically problems associated with abnormal renal
      function, hypersensitivity reactions, and thrombotic complications.

PMID- 9563399
TI  - Creutzfeldt-Jakob disease and transfusion safety: tilting at icebergs?

PMID- 9563400
TI  - Hemolysis associated with transplantation.

PMID- 9563401
TI  - The relationship between the duration of platelet storage and the development of
      transfusion reactions.
AB  - BACKGROUND: The incidence of platelet transfusion reactions may depend partly on
      the length of storage. The influence of reactions on the effectiveness of
      platelet transfusions is not known. STUDY DESIGN AND METHODS: Platelet
      transfusion reactions, identified by prospective monitoring, were analyzed for
      the effects of component type, recipient lymphocytotoxic antibodies, bacterial
      contamination, and duration of storage. Posttransfusion corrected count
      increments (CCIs) were used to evaluate the effectiveness of transfusions
      associated with reactions by comparing them to those of randomly selected
      transfusions without reactions. RESULTS: Reactions accompanied 4 percent of the
      4926 transfusions given and included 119 febrile nonhemolytic transfusion
      reactions, 62 allergic reactions, and 13 reactions with features of both.
      Platelet concentrates contained a mean of 0.5 x 10(8) white cells per unit.
      Lymphocytotoxic antibodies were detectable in 20 of 84 recipients tested
      proximate to a reaction. Bacterial cultures from 4 of 81 units were positive; 1
      unit was associated with fatal Enterobacter sp. sepsis. The incidence of febrile
      nonhemolytic transfusion reactions but not allergic reactions was related to
      platelet storage duration. The CCI was not significantly different for
      transfusions associated with reactions (10.97 [median, range 0-72.5; n = 165]) or
      not so associated (13.1 [median, range 0-39.5; n = 174]) (p = 0.08). CONCLUSION:
      The incidence of febrile nonhemolytic transfusion reactions but not allergic
      reactions appears to be related to the duration of platelet storage. Transfusion
      reactions may not have an adverse impact on the effectiveness of platelet
      transfusions.

PMID- 9563402
TI  - Comparison of the level of cytokine mRNA in buffy coat-derived platelet
      concentrates prepared with or without white cell reduction by filtration.
AB  - BACKGROUND: The generation of proinflammatory cytokines in platelet concentrates
      (PCs) by white cells is thought to be implicated in febrile nonhemolytic
      reactions. Furthermore, other cytokines could be generated in the PCs as signs of
      white cell activation when PCs are prepared from a pool of buffy coats (BCs). The
      number of white cells in the PCs is crucial to cytokine generation. STUDY DESIGN
      AND METHODS: Each of the PCs (n = 12) was prepared from a pool of BCs from four
      donors. Before storage, half of the BC-derived PCs (BC-PCs) were white cell
      reduced by filtration. The BCs and the unfiltered and filtered BC-PCs were
      assayed for the presence of cytokine mRNA (i.e., interleukin [IL]-1beta, IL-6,
      tumor necrosis factor alpha [TNFalpha], IL-8, IL-2, and interferon gamma [IFN
      gamma]) by the use of competitive reverse transcription-polymerase chain
      reaction. RESULTS: No mRNA of cytokines with pyrogenic activity, that is, IL
      1beta, IL-6 and TNFalpha, was detected in either the filtered or the unfiltered
      BC-PCs. Likewise, IL-2 mRNA was not found in any of the BC-PCs. IFN-gamma mRNA,
      however, was detected in the unfiltered BC-PCs but not in the filtered BC-PCs. IL
      8 mRNA was found in both the unfiltered and the filtered BC-PCs, but with a lower
      frequency in the filtered BC-PCs. CONCLUSION: The unfiltered BC-PCs produced in
      the top-and-bottom bag system contain traces or undetectable levels of the
      investigated cytokine mRNA. The results can be used in defining consensus
      recommendations for the use of filtered and unfiltered blood components.

PMID- 9563403
TI  - Reduction of plasma volume after storage of platelets in CP2D.
AB  - BACKGROUND: There has been concern that further deterioration might occur if
      stored platelets are centrifuged to reduce their volume. Although such
      centrifugation appears to have minimal effect on platelets in CPDA-1 (osmolarity,
      470 mOsm) there is no information on the situation with CP2D (580 mOsm). STUDY
      DESIGN AND METHODS: Platelet concentrates from CP2D packs were sampled at 1 and 5
      days and after centrifugation was used to reduce the plasma volume to 10 mL. The
      aggregation, hypotonic shock response, morphology, pH, and lactate, glucose, pCO2
      and pO2 levels were assessed, and values were compared to those seen with CPDA-1.
      In addition, blood was collected from the same donors into both CP2D and standard
      sodium citrate anticoagulant in an anticoagulant-to-blood ratio of 1:8 and the
      aggregation response of the fresh platelets was measured. RESULTS: Collection of
      blood into CP2D results in an immediate reduction of the platelet aggregation
      response when compared to that found after collection of blood into sodium
      citrate or CPDA-1. Aggregation is further decreased after storage; however, these
      changes and those for hypotonic shock, pH, lactate, glucose, and pCO2 are similar
      to those seen for CPDA-1. Additional centrifugation did not cause further change.
      CONCLUSION: Platelets stored in CP2D have reduced in vitro function after 5 days
      of storage, but subsequent centrifugation to reduce the plasma volume does not
      further alter these platelets.

PMID- 9563404
TI  - Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO
      incompatible allogeneic bone marrow transplant.
AB  - BACKGROUND: A patient who received an ABO-incompatible allogeneic bone marrow
      transplant experienced three episodes of immune hemolytic anemia due to multiple
      red cell (RBC) alloantibodies. CASE REPORT: A 41-year-old man with chronic
      myeloid leukemia received an ABO-incompatible bone marrow graft from his HLA
      identical brother. Selective removal of RBCs from donor marrow before transfusion
      was performed by centrifugation using a continuous-flow blood cell separator. The
      patient was given group O Rh-positive RBCs and group A Rh-positive platelets.
      Prophylaxis for graft-versus-host disease consisted of cyclosporine and
      methotrexate. The patient experienced three hemolytic episodes, on Days 21, 35,
      and 160 which were due to different RBC alloantibodies (anti-K, anti-Jk(b), anti
      M, IgG anti-A) produced by host lymphocytes surviving the conditioning regimen.
      RESULTS: The patient was group O, Jk(b-), and the marrow donor was group A,
      Jk(b+). After the first hemolytic episode (Day 21), immunohematologic studies
      showed group O RBCs and a positive direct antiglobulin test (IgG+, C3d+).
      Antibody screening test and eluate studies detected anti-M, anti-Jk(b), and anti
      K. During the second hemolytic episode (Day 35), the patient's blood group showed
      a mixed population of group A and group O RBCs. The direct antiglobulin test was
      positive (IgG+, C3d+). Anti-M, anti-Jk(b), and IgG anti-A were detected in the
      serum. Eluates made from the recipient's RBCs showed the same specificity as
      serum antibodies. During the third hemolytic episode (Day 160), a mixture of
      group O and group A RBCs was still present, the direct antiglobulin test was
      positive (IgG+, C3d-), and anti-Jk(b) and IgG anti-A were observed in the serum
      and in an eluate made from the patient's RBCs. CONCLUSION: This is the first
      reported case of severe immune hemolytic anemia due to multiple RBC
      alloantibodies after an allogeneic bone marrow transplant. The time of appearance
      and the specificity of the antibodies strongly suggest that they were produced by
      residual recipient lymphoid cells.

PMID- 9563405
TI  - An enzyme-linked immunosorbent assay for the quantitation of IgG anti-D and IgG
      subclasses in the sera of alloimmunized patients.
AB  - BACKGROUND: IgG subclass composition of maternal alloantibodies to the D antigen
      seems to play a role in the severity of hemolytic disease of the newborn. The
      subclassing of IgG anti-D is usually performed by hemagglutination techniques,
      but the results are not quantitative and sometimes are difficult to interpret.
      Thus, there is a need for quantitative methods. STUDY DESIGN AND METHODS: The aim
      of this study was to develop an enzyme-linked immunosorbent assay (ELISA) for the
      quantitation of specific IgG anti-D and IgG subclasses in the sera of
      alloimmunized patients. Group O R1R2 red cells were sensitized with anti-D. Red
      cell membranes were solubilized with nonionic detergent. IgG and IgG subclasses
      were measured by a sensitive and reproducible immunocapture ELISA. A serum
      calibrated for its IgG subclass content was used as a reference, and the anti-D
      preparation 68/419 was used as an internal control. Optimal conditions for the
      detection of IgG anti-D and IgG subclasses by ELISA were studied. The absolute
      concentration and the proportions of IgG subclasses were determined in the sera
      of 14 pregnant women. RESULTS: A close parallelism was observed between dilutions
      of the IgG reference serum and the IgG anti-D solubilized from sensitized RBCs.
      The sum of IgG anti-D subclass concentrations, determined by the ELISA,
      correlated well with other quantitative methods. CONCLUSION: The method described
      is sensitive and can be used routinely for the quantitative determination of
      specific IgG anti-D and IgG subclasses in sera.

PMID- 9563406
TI  - Quantitation of white cell subpopulations by polymerase chain reaction using
      frozen whole-blood samples. Viral Activation Transfusion Study.
AB  - BACKGROUND: Previous methods for processing whole blood (WB) for nucleic acid
      analyses of white cells (WBCs) required fresh blood samples. A simple protocol
      that involves the freezing of WB for quantitative polymerase chain reaction (PCR)
      analyses was evaluated. STUDY DESIGN AND METHODS: Controlled studies were
      conducted in which paired fresh and frozen WB preparations were analyzed. The
      integrity of WBCs in the frozen WB samples was first assessed by flow cytometry
      using CD45 fluorescence, and calibration beads to quantitate recovery of WBC
      subsets. PCR of an HLA-DQ-A sequence was used to quantitate residual WBCs in a
      double-filtered red cell (RBC) component spiked with serial dilutions of WBCs, as
      well as in 51 filtered RBCs and 19 filtered platelet concentrates. Y-chromosome
      specific PCR was used to quantitate male WBCs in five female WB samples spiked
      with serial dilutions of male WBCs and in serially collected frozen WB samples
      from four females transfused with male blood components. RESULTS: By flow
      cytometry, all major WBC subpopulations in frozen-thawed WB were quantitatively
      recovered and immunologically intact, although they were nonviable. HLA-DQ-A PCR
      quantitation of a dilution series from 8 to 16,700 per mL of WBCs spiked into
      double-filtered RBCs showed linear correlation of the results with both fresh and
      frozen preparations of the expected WBC concentrations (r2 = 0.98, p<0.0001 for
      both), without significant difference between observed and expected values
      (p>0.05). Y-chromosome-specific PCR results in female WB samples spiked with male
      WBCs were not significantly different in fresh and frozen preparations over a 3
      log10 range of male cells. The results of WBC survival studies on frozen WB
      samples were consistent with previous observations in fresh blood samples.
      CONCLUSION: Direct freezing of WB enables subsequent recovery of WBCs for
      quantitative PCR analyses, with results comparable to those of fresh
      preparations.This protocol should facilitate wider implementation of nucleic acid
      based analyses for quality control of WBC-reduced components, as well as for
      prospective clinical studies of microchimerism in transfusion and transplant
      recipients.

PMID- 9563407
TI  - Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from
      all seropositive and most seronegative healthy blood donors over time.
AB  - BACKGROUND: A poor correlation between cytomegalovirus (CMV) seroreactivity and
      the risk of CMV transmission prompted an investigation of the presence of CMV DNA
      in peripheral blood mononuclear cells (PBMNCs) from seropositive and seronegative
      blood donors. Because latent CMV exists in monocytes, monocyte-enriched cells
      were analyzed separately. STUDY DESIGN AND METHODS: Samples from 270 blood donors
      were tested with a sensitive polymerase chain reaction (PCR) test that detects
      two CMV genes, and the results were correlated to CMV serology. Cross-reactivity
      with other herpesvirus genes was not recorded. RESULTS: PCR testing demonstrated
      that 71 percent of seropositive donors harbor CMV in PBMNCs. Thus, not all
      seropositive donors were CMV DNA positive when individual samples were tested.
      Tests repeated over a period of time showed that all seropositive individuals
      were positive. Increased sensitivity was obtained with enriched monocytes. Among
      seronegative donors, 55 percent harbored CMV DNA in monocyte-enriched PBMNCs,
      while 14 percent had CMV DNA in PBMNCs. CONCLUSION: All seropositive donors
      harbored latently infected PBMNCs, as demonstrated by the testing of samples
      collected over time. In addition, a substantial proportion of seronegative
      individuals are CMV carriers and might transfer infection. The findings concur
      with clinical evidence of CMV transmission by blood components from seronegative
      individuals and with in vitro reactivation of CMV in PBMNCs from seronegative
      donors.

PMID- 9563408
TI  - Risk factors for HIV seropositivity among first-time blood donors in Zimbabwe.
AB  - BACKGROUND: Factors associated with an increased likelihood of HIV infection
      among newly recruited blood donors in Zimbabwe are identified. Their feasibility
      as criteria for exclusion from donation is assessed. STUDY DESIGN AND METHODS: A
      self-administered survey including demographic and behavioral questions was
      completed by 1199 first-time, volunteer blood donors in Harare, Zimbabwe. Methods
      for subject recruitment and laboratory screening followed usual blood bank
      protocols. RESULTS: Fifteen percent of subjects were HIV positive. Factors
      significantly associated with HIV seropositivity at the p<0.05 level included
      recruitment venue, age, marital status, donor residence, residence of primary
      partner, occupation, history of sexually transmitted disease, and condom use. An
      exclusion strategy based on donor age, condom use, recruitment venue, sexually
      transmitted disease history, and residence of primary partner would exclude a
      large proportion of HIV-infected donors without substantial loss of uninfected
      donors. CONCLUSIONS: Exclusion of donors who are likely to be infected with HIV
      is a sound policy for improving blood safety and reducing operating costs
      worldwide. Identification of efficient donor selection criteria requires
      knowledge of the local epidemiology of HIV infection and the asking of questions
      that are likely to be answered accurately.

PMID- 9563409
TI  - Platelet collection with the Amicus and the AS.TEC 204 blood cell separators.
AB  - BACKGROUND: Platelet collection with two new blood cell separators was compared
      with respect to platelet yield, separation efficiency, white cell (WBC)
      contamination, and measures of component quality. Both machines offer a menu for
      the collection of a desired platelet yield. The harvesting of a definite platelet
      yield is a means of collecting a standardized therapeutic platelet dose. STUDY
      DESIGN AND METHODS: One hundred seventy-two platelet collections were carried out
      with different protocols in the two devices (Amicus and AS.TEC 204). For that
      reason, healthy donors underwent plateletpheresis procedures using the continuous
      and discontinuous-flow systems. Separations with a definite endpoint volume and
      the option of collecting a desired platelet yield of 5.5 x 10(11) in the Amicus
      and 3.3 x 10(11) in the AS.TEC 204 machine were investigated. RESULTS: With the
      Amicus blood cell separator, platelet yield (5.02+/-0.46 x 10[11]) and separation
      efficiency (66.9+/-6.2%) were significantly higher than those with the AS.TEC 204
      (3.02+/-0.62 x 10[11] and 46.4+/-6.7%, respectively). There was less deviation
      between the platelet yield and the desired platelet yield in the AS.TEC 204
      machine than in the Amicus device. WBC contamination was 2.06+/-2.91 x 10(6) in
      components obtained from the AS.TEC 204 machine, and 87.5 percent of the platelet
      concentrates had a WBC content <5 x 10(6). None of the components from the Amicus
      device contained more than 5 x 10(6) WBCs. Except for platelet morphology score,
      measures of component quality were almost equal in the platelet concentrates
      obtained from the studied machines. CONCLUSION: Platelet yield and separation
      efficiency were significantly higher in the Amicus blood cell separator. The
      collection of a desired platelet yield was better achieved with the AS.TEC 204
      device.

PMID- 9563410
TI  - Prevalence and infectivity of hepatitis G virus and its strain variant, the GB
      agent, in volunteer blood donors in Taiwan.
AB  - BACKGROUND: The prevalence of hepatitis G virus (HGV) and its strain variant, the
      GB agent (GBV-C) is high in non-virus-inactivated plasma products, but,
      persistent infection in recipients is relatively low. STUDY DESIGN AND METHODS:
      Stored samples from transfusion donors and recipients in a prospective study of
      posttransfusion hepatitis were tested for HGV RNA and antibody to the E2 protein
      (anti-E2). RESULTS: Thirty-two (2.1%) of the 1500 qualified donors were positive
      for HGV RNA. Twenty-four persons had received a transfusion of blood from one of
      these 32 viremic donors. Of these 24 recipients, 3 were positive for HGV RNA
      before transfusion. Of the remaining 21 recipients, 8 became viremic after
      transfusion, while the other 13 were not infected. Four of the eight infected
      recipients were persistently positive for HGV RNA, while four became negative in
      1 to 3 years. Three of the four patients with HGV clearance seroconverted to anti
      E2 positivity. Comparison of the viral titer, viral sequences at E2, storage
      period of blood donations, and clinical data in the infected and noninfected
      recipients revealed no significant differences. However, the noninfected
      recipients seemed to have a higher prevalence of anti-E2 before transfusion.
      CONCLUSION: The prevalence of HGV viremia in volunteer blood donors in Taiwan is
      2.1 percent, and blood from 0.6 percent of them actually causes HGV infection in
      the recipients. In half of infected recipients, clearance of HGV occurs. Anti-E2
      appears in most recipients whose viremia is cleared.

PMID- 9563411
TI  - Adverse reactions associated with autologous blood transfusion: evaluation and
      incidence at a large academic hospital.
AB  - BACKGROUND: It is acknowledged that autologous blood is the safest for the
      patient to receive. However, it is generally not appreciated that transfusion
      reactions to autologous blood may occur, despite the fact that it is the
      patient's own blood. STUDY DESIGN AND METHODS: A retrospective review of all
      transfusion reactions reported to a hospital transfusion service from 1991
      through 1996 was performed, and all reactions to autologous blood were further
      investigated. RESULTS: Reported adverse reactions to autologous blood composed
      2.1 percent of all transfusion reactions investigated in the hospital, involving
      0.16 percent (15/9,353) of all transfused preoperatively donated autologous red
      cell units and 0.027 percent (5/18,506) of all intraoperatively salvaged units.
      Further investigation revealed that 60 percent (12/20) of these adverse reactions
      were felt to be clinically important and directly attributable to the autologous
      blood transfusion. Adverse reactions included febrile nonhemolytic (5) and
      allergic (4) reactions, an acute hemolytic transfusion reaction secondary to a
      clerical error (1 intraoperatively salvaged unit), and other nonsignificant
      adverse reactions (2). Eight adverse reactions were determined these reactions to
      be unrelated to the autologous transfusion. CONCLUSION: Despite the fact that the
      blood given is the patient's own blood, transfusion reactions to autologous blood
      do occur. As it is for allogeneic transfusion, any suspected adverse reaction to
      autologous blood transfusion should be investigated.

PMID- 9563413
TI  - Transmission of hepatitis G virus in patients with angioedema treated with steam
      heated plasma concentrates of C1 inhibitor.
AB  - BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause
      acute and chronic transfusion-transmitted infections. Patients with complement
      component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections
      through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples
      from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH
      concentrates, 23 who received steam-heated concentrates, and 42 untreated
      patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested
      polymerase chain reaction (PCR). The samples were also tested for antibodies to
      the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked
      immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7
      (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42
      previously untreated patients. HGV RNA was as common in the 19 patients treated
      with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs.
      17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified
      concentrates than among those given steam-heated concentrates (26 vs. 0%, p =
      0.014). HCV RNA was more frequently detected in treated patients than in
      untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified
      concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p
      = 0.003). Only one HGV RNA-seropositive patient had elevated serum
      aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was
      transmitted by both unmodified and steam-heated concentrates, but it caused
      persistent viremia in a minority of the cases and was rarely associated with
      liver disease.

PMID- 9563412
TI  - Viremia, genetic heterogeneity, and immunity to hepatitis G/GB-C virus in
      multiply transfused patients with thalassemia.
AB  - BACKGROUND: Thalassemia patients are at high risk for posttransfusion hepatitis.
      Hepatitis G virus (HGV) has been suspected of being responsible for acute and
      chronic hepatitis. STUDY DESIGN AND METHODS: The prevalence of HGV infection, its
      possible association to liver disease, the genetic heterogeneity among the
      various HGV isolates, and immunity to HGV were studied in 36 thalassemia patients
      with reverse transcriptase-polymerase chain reaction assay and sequence analysis.
      RESULTS: HGV RNA was detected in seven patients (19.4%), only two of whom had
      evidence of hepatitis C virus infection as well. Sequence analysis of the NS3
      gene from isolates of the five patients infected with HGV alone revealed 84.7 to
      90.9 percent homology at the nucleotide level. Prolonged HGV viremia was not
      associated with significant liver enzyme elevation. All five patients were
      chronically infected with the same viral strain. E2 antibodies were detected in
      57 percent of the HGV-nonviremic patients and in only 1 of 7 viremic patients.
      CONCLUSION: HGV is associated with persistent viremia but not with significant
      biochemical evidence of liver damage. There is some genetic heterogeneity among
      HGV isolates from thalassemia patients in Israel.

PMID- 9563414
TI  - Donor pool size and the risk of blood-borne Creutzfeldt-Jakob disease.

PMID- 9563415
TI  - Transfusion-acquired hepatitis C virus infection in a Canadian population,
      October 1983 through June 1985.

PMID- 9563416
TI  - White cell reduction by filtration may significantly decrease human T
      lymphotropic virus type 1 Tax sequences and Tax-encoded proteins in blood used
      for transfusion.

PMID- 9563417
TI  - Enzyme-only blood group alloantibodies in pregnancy.

PMID- 9563418
TI  - The apheresis anticoagulant.

PMID- 9563419
TI  - Platelet activation and interval between plateletpheresis.

PMID- 9563420
TI  - Integrated diagnostic and treatment approach for the medical patient who has had
      psychologic trauma.
AB  - BACKGROUND: Physicians often treat patients with physical illnesses that have a
      functional component. Investigators have discovered that many of these patients
      have unresolved emotional problems associated with histories of trauma and abuse.
      METHODS: Abused and traumatized patients with medical complaints often seek
      medical help. Empathic nonpsychiatrist physicians play an important role in the
      care of these patients. The physician's efforts can be augmented by a trained RN
      to provide supportive stress training and nutrition education and by a mental
      health professional to provide psychotherapy when needed. RESULTS: In the case
      presented, the patient had symptomatic improvement when her physician
      empathically provided medical treatment, involved the staff and a trained RN in
      the healing effort, and made an appropriate referral to a mental health
      professional. CONCLUSION: This unified diagnostic and treatment approach for
      traumatized patients with medical problems can be rewarding, efficacious, and
      cost effective.

PMID- 9563421
TI  - Abdominal compartment syndrome.
AB  - BACKGROUND: The abdominal compartment syndrome (ACS) is a newly appreciated and
      potentially fatal consequence of increased intra-abdominal pressure. It can be
      due to either trauma or surgery, as well as numerous medical conditions.
      Prolonged, unrelieved elevation of intra-abdominal pressure can produce pulmonary
      compromise, renal impairment, cardiac failure, shock, and death. A high index of
      suspicion is imperative. Measurement of the intravesical pressure provides a
      urometric window for detecting and monitoring this condition. CONCLUSIONS:
      Reopening the abdominal incision (decompressive celiotomy) has proven a life
      saving intervention. Use of delayed wound closure (staged celiotomy) may prevent
      development of this condition in high-risk surgical patients. It is urgent that
      all physicians, and surgeons in particular, be alerted to this potentially lethal
      complication.

PMID- 9563422
TI  - Invasive disease due to group A beta-hemolytic streptococci: continued occurrence
      in children in North Carolina.
AB  - BACKGROUND: We have previously reported a significant increase beginning in the
      late 1980s in the incidence of invasive disease due to group A beta-hemolytic
      streptococci (GABS) in children admitted to our hospital. To determine subsequent
      trends in epidemiology, we have continued to monitor cases. METHODS: We
      prospectively monitored cases of invasive disease due to GABS at Brenner
      Children's Hospital during the 5 1/2 years (July 1, 1990, to December 31, 1995)
      since our last report. RESULTS: Twenty-five patients had GABS isolated from
      normally sterile sites. Their presentations were varied. One patient had
      necrotizing fasciitis and one had toxic shock-like syndrome. The one death was
      that of a newborn infant with sepsis and meningitis. The proportion of GABS
      infections associated with varicella was significantly greater during this period
      (7/25, 28%) than during the period 1983 to 1990 (1/22, 5%). Isolates were
      available tor study from 24 patients. Serotypes were M1 (4), M3 (4), M6 (2), M12
      (3), M22 (3), M75 (1) and M-nontypeable (7). The number of cases of invasive
      disease seen annually from 1983 through 1995 also is reviewed. CONCLUSIONS: The
      resurgence of invasive disease due to GABS in children noted in the late 1980s
      continues through the first half of the 1990s. The clinical manifestations are
      varied as are the causative M-types. As almost one third of cases in this series
      were associated with varicella infection, widespread use of the varicella vaccine
      may lead to a decrease in the incidence of invasive GABS disease.

PMID- 9563424
TI  - Patient participation in colon cancer screening programs.
AB  - BACKGROUND: The objectives of this study were to survey compliance and identify
      factors that influence continued participation with periodic colon cancer
      screening guidelines once patients are seen for their first screening. METHODS:
      The study group consisted of 95 patients who had initial fecal occult blood tests
      (FOBT) and flexible sigmoidoscopy (FS) in 1991 as part of a gastroenterologist
      directed, aggressively managed colon cancer screening registry. Regular notices
      are sent to patients and their primary care provider for annual FOBT and FS at 3-
      to 5-year intervals. RESULTS: Of 70 (74%) reviewed, 2 had died and 3 were having
      colonoscopic surveillance. Thirty-two of the 65 (49%) contacted eligible study
      subjects were no longer participating. Reasons stated were as follows: unaware
      that screening was due (14), too busy (6), unpleasant experience (3), and change
      to insurance provider that did not cover screening (9 [commercial-3, managed care
      1, Medicare-5]). CONCLUSIONS: Despite aggressive program management, 44% of
      nonparticipators reported that they were unaware that screening was due. Sixteen
      percent of those who did not continue to participate had graduated to Medicare,
      which did not cover screening costs. Factors that influence continued
      participation need to be considered in the design of public education and
      marketing promotions.

PMID- 9563423
TI  - Reactive airways dysfunction syndrome after exposure to dinitrogen tetroxide.
AB  - BACKGROUND: Reactive airways dysfunction syndrome (RADS) is characterized by
      persistent bronchial hyperreactivity and asthmatic symptoms in a previously
      healthy individual after a single intense exposure to an irritant fume, vapor, or
      gas. On October 23, 1995, a cloud of dinitrogen tetroxide (N2O4) escaped from a
      railroad tanker car in Bogalusa, Louisiana, exposing an estimated 4,000 citizens
      to the gas. METHODS: A sample of 234 patients with respiratory complaints after
      the spill received a complete history and physical examination, a symptom
      questionnaire, and pulmonary function tests. Patients whose previously
      undocumented asthma-like symptoms persisted for 3 months after exposure to N2O4
      had methacholine challenge testing. RESULTS: Of the 234 patients evaluated, six
      met the criteria for a diagnosis of RADS. The distance of these six patients from
      the source of the leak, their durations of exposure, and initial symptoms were
      not different from those of the sample patients who did not have RADS.
      CONCLUSIONS: After evaluation of 234 symptomatic patients who were exposed to
      N2O4, we diagnosed six cases of RADS. There were no demographic characteristics
      or initial symptoms that identified patients who were at risk of having this
      syndrome. We believe we are the first to report cases of RADS due to N2O4
      exposure.

PMID- 9563425
TI  - The risk of purified protein derivative positivity in homeless men with psychotic
      symptoms.
AB  - BACKGROUND: Homeless people with mental illness have relatively high rates of
      human immunodeficiency virus, comorbid antisocial personality disorder, and may
      be homeless more frequently and for greater lengths of time. All of these factors
      may increase the risk of tuberculosis. METHODS: Our study was done to ascertain
      if homeless men with psychotic disorders are at an increased risk for
      tuberculosis infection. One hundred fifty homeless men were interviewed and given
      purified protein derivatives (PPDs) at a downtown shelter in New Orleans,
      Louisiana, during a 3-month period. RESULTS: The findings show a strong
      relationship between psychotic disorders and positive PPDs, with a relative risk
      of 4.48. CONCLUSIONS: Homelessness and mental illness present barriers to seeking
      and completing treatment for medical illnesses such as tuberculosis. Use of
      services may be low even when available; therefore, homeless men with psychotic
      disorders may be serving as a reservoir for tuberculosis.

PMID- 9563426
TI  - Remember to consider dermatophyte infection when dealing with recalcitrant
      dermatoses.
AB  - BACKGROUND: Superficial fungal infections of the skin are among the most common
      infections encountered in medicine. The diagnosis is easily confirmed with simple
      office-based procedures. In certain clinical situations, the diagnosis can be
      elusive. METHODS: We analyzed clinical data on five patients who came in referral
      for treatment of a recalcitrant dermatosis. RESULTS: All patients had their
      diagnosis confirmed by a positive potassium hydroxide preparation from skin
      scrapings or by a skin biopsy positive for fungal elements. All showed clinical
      improvement and ultimate resolution of their skin lesions with topical and/or
      systemic antifungal therapy. CONCLUSIONS: Diagnosis can be complicated by
      previous use of corticosteroid-containing topical and/or systemic agents, a
      clinical history closely resembling that of a photosensitive disorder, and a lack
      of clinical-histopathologic correlation. Laboratory procedures and skin biopsy of
      an ambiguous appearing lesion can be diagnostic, but an accurate diagnosis is
      dependent on communication between the clinician and the pathologist. We
      recommend that office-based procedures be done early in treatment so that
      subsequent efforts can be directed toward providing appropriate therapies.

PMID- 9563427
TI  - Emergency medicine practice systems in Louisiana.
AB  - BACKGROUND: We surveyed emergency medicine practice systems in Louisiana.
      METHODS: We surveyed 105 emergency department (ED) directors in Louisiana
      requesting annual ED volume, hospital type, physician coverage scheduled, type of
      documentation used, use of physician extenders, use of minor care or observation
      areas, and employment status of emergency physicians. RESULTS: Directors of 71
      EDs responded. Eighty-six percent of emergency physicians were employed as
      independent contractors. Public and teaching EDs accounted for 51% and 23%,
      respectively. Mode of documentation was handwritten in 56% and dictated in 21%;
      23% used a combination. Physician extenders were used in 7%, with 4% using
      physician assistants and nurse practitioners. Minor care areas were used in 17%,
      observation areas in 25%. Nonteaching EDs had a significantly less mean annual
      volume and physician hours scheduled; they also treated significantly fewer
      patients per hour. Emergency departments using dictation, physician extenders, or
      accessory care areas had significantly greater mean annual patient volumes.
      CONCLUSIONS: Emergency departments in teaching hospitals, using dictation,
      physician extenders, and accessory care areas, have significantly greater system
      productivity than nonteaching hospitals.

PMID- 9563428
TI  - Chronic medications in the perioperative period.
AB  - BACKGROUND: While most chronic medications can be safely continued in the
      perioperative period, decisions regarding certain medications remain
      controversial. METHODS: We mailed a questionnaire to all 150 anesthesiology
      program directors in the United States, with 113 (75%) responding. Opinions
      regarding preoperative discontinuance or modification of selected medications
      were assessed. RESULTS: Antiplatelet agents are typically discontinued
      preoperatively, although the number of days varies widely. Few respondents
      discontinue tricyclic antidepressants, oral contraceptives, diuretics, or oral
      hypoglycemic agents. For a patient on insulin, the most popular regimen is half
      the patient's usual dose of neutral protamine Hagedorn insulin (50%) or no
      preoperative insulin (37%), whereas an insulin infusion for tight control was
      rarely advised. Respondents varied widely in their approach to steroid coverage,
      their cancellation of elective operations in patients with inadvertent aspirin
      ingestion, and the length of time before surgery they would discontinue warfarin.
      In patients with chronic atrial fibrillation, 72% of respondents favored use of a
      heparin window preoperatively. CONCLUSIONS: Practice variations regarding insulin
      regimens, steroid coverage, aspirin, and anticoagulants reflect a lack of firm
      evidence favoring one approach.

PMID- 9563429
TI  - Effectiveness of conjugated estrogen in orthotopic liver transplantation.
AB  - BACKGROUND: A retrospective study was conducted at a university hospital to
      determine the efficacy of conjugated estrogen in reducing blood product
      transfusion during orthotopic liver transplantation. METHODS: The charts of
      patients who had orthotopic liver transplantation were retrospectively reviewed.
      Only those having a reaction time > 30 mm or 15 minutes (normal = 19 mm to 28 mm)
      on computerized thromboelastogram (CTEG) at the beginning of surgery were
      included. One group of patients received a first dose of conjugated estrogen (100
      mg i.v.) at the beginning of the case and a second dose (100 mg i.v.) just after
      reperfusion of the new graft. The control group did not receive estrogen. The two
      groups were similar in age, weight, first TEG measurements, final intraoperative
      hemoglobin concentration and platelet count. Blood products were given in
      response to hematocrit and CTEG measurements, which were determined every hour
      during surgery. RESULTS: The two groups did not differ in units of
      cryoprecipitate and platelets administered, but the intraoperative requirements
      for red blood cells and fresh frozen plasma were significantly lower in the
      estrogen group than in the control group. CONCLUSIONS: Administration of
      conjugated estrogen is associated with a statistically significant decrease in
      use of red blood cells and fresh frozen plasma during orthotopic liver
      transplantation.

PMID- 9563430
TI  - Prevalence of methicillin-resistant Staphylococcus aureus in a dermatology
      outpatient population.
AB  - BACKGROUND: The number of methicillin-resistant STaphylococcus aureus (MRSA)
      infections in the hospital setting is increasing but little is known of its
      prevalence in the community. In a 1986-1987 study, the prevalence in dermatology
      outpatient clinics was <0.9%. This study reports changes in the same facilities
      from 1988 through 1996. METHODS: Culture results and antimicrobial susceptibility
      patterns were reviewed for the population for the period 1988 through 1996.
      RESULTS: We report a gradual increase of MRSA from 1.5% of all strains of
      Staphylococcus aureus in 1988 to 11.9% in 1996 in these outpatient facilities.
      Susceptibility data indicate that the MRSA strains isolated in 1996 are more
      resistant to oral agents such as ciprofloxacin and tetracycline, while all
      strains remain susceptible to the intravenous agent vancomycin. CONCLUSION: The
      prevalence of MRSA in the community is increasing and should be considered when
      selecting a treatment regimen for staphylococcal infections.

PMID- 9563431
TI  - Anemia and red cell distribution width at the 12-month well-baby examination.
AB  - BACKGROUND: Screens for anemia are among the most commonly done laboratory tests
      in children. The red cell distribution width (RDW) has been proposed as a
      diagnostic aid in the evaluation of pediatric anemias, but no prospective studies
      have been published describing its use. METHODS: A screening hematocrit
      determination done at the 12-month well-baby examination in 970 healthy infants
      yielded 62 low values (< 33%), 31 of which were confirmed by heel stick complete
      blood count (CBC). After a 1-month trial of iron therapy, those with a rise in
      hemoglobin of at least 1 g/dL were considered to have iron-deficiency anemia.
      Nonresponders, after review of clinical and laboratory data (CBC, lead screen,
      and sickle screen), had hemoglobin electrophoresis if indicated. RESULTS:
      Abnormalities detected were iron deficiency, alpha-thalassemia, and hemoglobins
      SC and AS. These conditions were detected in 9 of 11 infants with abnormal RDW
      and none of 9 with normal RDW. CONCLUSIONS: The RDW alone appears to be
      predictive of identifiable causes of anemia when used in screening 12-month-old
      babies who are otherwise healthy.

PMID- 9563432
TI  - Predilection for frailty remedial strategies among black and white seniors.
AB  - BACKGROUND: Frailty prevention and remedial programs based on exercise, hormone
      replacement, and vitamin supplementation are becoming available for use with
      older patients, but success of these programs depends largely on seniors'
      willingness to participate. METHODS: We evaluated preferences for specific
      aspects of these programs using a sample of 359 older persons recruited from
      potential delivery sites. Main effects and subgroup analyses were done. RESULTS:
      Subjects preferred stretching, chair-based, walking, and dynamic balance
      exercises over lifting weights, dancing, hormone and vitamin therapy; exercising
      alone in their own homes over exercising in groups; and vitamins over hormones.
      Preferences were affected to some extent by sex, race, recruitment site, and
      functional status. However, subjects' willingness even to consider exercise was
      rarely as high as the desired levels of participation set forth in Healthy People
      2000. CONCLUSIONS: Physicians and public health authorities need to educate older
      persons about effective methods to prevent or treat frailty.

PMID- 9563433
TI  - Wegener's granulomatosis manifested as a perirectal abscess.
AB  - Wegener's granulomatosis is a serious systemic vasculitis that needs to be
      diagnosed promptly to limit morbidity and mortality. Atypical presentations of
      this disease are not uncommon. This case illustrates a rare manifestation of
      Wegener's granulomatosis (ie, perirectal abscess) and the value of the
      antineutrophil cytoplasmic antibody in conjunction with supporting pathology.

PMID- 9563434
TI  - Anesthetic implications of tetanus.
AB  - The patient described had generalized tetanus and required anesthetic care during
      debridement of a lower extremity wound. Despite widespread vaccination, which
      limits the incidence of the disease in the United States, tetanus remains a major
      health problem in developing countries. The pathophysiology of tetanus, its
      clinical manifestations, and current treatment options are discussed, and the
      anesthetic implications of the disease are reviewed.

PMID- 9563435
TI  - Endogenous endophthalmitis due to Serratia marcescens.
AB  - Endogenous or metastatic bacterial endophthalmitis is a severe, sight-threatening
      infection of the vitreous humor that is only rarely due to Serratia marcescens.
      We report the case of a hemodialysis-dependent diabetic patient who had
      endogenous endophthalmitis of the right eye due to S marcescens, presumably from
      an infected dialysis catheter. The patient had total visual loss in the affected
      eye, which required enucleation.

PMID- 9563436
TI  - Unilateral absent pulmonary perfusion due to bronchogenic carcinoma.
AB  - Ventilation-perfusion lung scans are commonly done in the diagnosis of pulmonary
      thromboembolic disease. We describe a patient in whom absent perfusion involving
      an entire lung was due to bronchogenic carcinoma. Echocardiography and chest
      computed tomography were essential tests in evaluating a nonembolic etiology.

PMID- 9563437
TI  - Diaphragm-like strictures of the ileum associated with NSAID use: a rare
      complication.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for many
      conditions including arthritis. A rare complication of their use is diaphragm
      like strictures of the small and large intestines. A 65-year-old woman with a 12
      year history of arthritis came to us with a 35-pound weight loss and anorexia.
      She had been taking piroxicam for 3 years. Evaluation including enteroclysis
      revealed multiple mid-ileal diaphragm-like strictures and proximal small bowel
      dilatation. The symptoms persisted despite discontinuance of the drug. Abdominal
      exploration with intraoperative enteroscopy revealed five ileal strictures within
      a short segment of bowel. Resection was done and completion enteroscopy showed no
      other strictures. The patient recovered uneventfully and had full resolution of
      the symptoms. We discuss the difficulties in diagnosis and management of this
      drug complication and briefly review the literature.

PMID- 9563438
TI  - Recurrent catamenial hemopneumothorax.
AB  - A case of recurrent hemorrhagic catamenial hemopneumothorax resulting from
      diffuse pleural endometriosis is presented. The pathogenesis of this rare entity
      is discussed, and the immediate and long-term surgical and medical options for
      therapy are reviewed.

PMID- 9563439
TI  - Nodular amyloidosis of the lung from intravenous drug abuse: an uncommon cause of
      multiple pulmonary nodules.
AB  - Bilateral pulmonary nodules in an immunocompromised host may offer a diagnostic
      dilemma. We present a case of a human immunodeficiency virus positive patient
      with history of intravenous drug abuse (IVDA) who was incidentally found to have
      bilateral multiple pulmonary nodules. She was diagnosed as having nodular
      pulmonary amyloidosis, presumably serum amyloid A derived (AA) in origin but
      confirmed not to be of amyloid light chain derived origin (AL), histologically
      associated with focal birefringent material and foreign body giant cell reaction,
      probably due to IVDA. Asymptomatic multiple pulmonary nodules in amyloidosis are
      usually of AL origin; however, recently similar changes have been found in the AA
      form in patients with Sjogren's syndrome or Crohn's disease. It has not been
      previously described in association with IVDA. Thus, this case documents a unique
      cause of bilateral pulmonary nodules due to amyloidosis consequent to IVDA.

PMID- 9563441
TI  - Massive periorbital lymphedema after excision of cutaneous malignancy.

PMID- 9563440
TI  - Perforated cecal adenocarcinoma manifested as thigh abscess.

PMID- 9563442
TI  - Latex allergy: surgical perspectives.

PMID- 9563443
TI  - Gastric cancer in Asia: progress and controversies in surgical management.
AB  - Considerable controversy surrounds the management of gastric cancer and this has
      largely overshadowed recent progress in our understanding of the epidemiology and
      molecular pathogenesis of the disease, and improvements in diagnostic and staging
      techniques. Differences identifiable in the molecular pathogenesis of the
      'intestinal' and 'diffuse' types of gastric cancer may help to unravel the
      biological behaviour of variants and ultimately influence therapeutic strategies.
      Endoscopic ultrasound is well established as being accurate for T staging and the
      introduction of laparoscopy, with or without ultrasound, is obviating unnecessary
      laparotomy in non-bleeding, non-obstructed patients. Controversies in surgery
      encompass the role of laparoscopic surgery in early gastric cancer, the extent of
      lymphadenectomy including para-aortic nodal dissection, resection of en bloc
      contiguous organ involvement, pancreatosplenectomy, left upper abdominal
      evisceration, and modes of reconstruction (pylorus-preserving gastrectomy, pouch
      formation) to enhance quality of life. Whereas adjuvant chemotherapy does not
      impact favourably on survival, emphasis has now shifted to neoadjuvant
      (induction) chemotherapy to downstage the disease. Preoperative regional
      chemotherapy and intra-operative hyperthermic chemotherapy or irradiation may
      prove to be of benefit in patients with resectable disease, but some scepticism
      still exists as to the usefulness of biological response modifiers (e.g. OK432,
      PSK) for adjuvant treatment. Ethical issues relating to cultural differences in
      Asia sometimes mitigate against adequate trial design (e.g. a surgery-alone
      control group or a no adjuvant therapy treatment group may be considered
      inappropriate) and this has understandably hindered acceptance in Western
      countries of the value of current management practices in Asia. These issues and
      the need for ongoing well-conducted randomized trials with prospective subset
      analysis are now being addressed.

PMID- 9563444
TI  - Nm23 gene expression in gastric carcinoma: an immunohistochemical study.
AB  - BACKGROUND: The gene Nm23 is thought to play a role in the suppression of tumour
      metastasis. Reduced expression of Nm23 is seen in a number of human cancers, and
      is associated with increased metastasis and reduced survival, most strongly in
      ductal breast and colorectal carcinomas. METHODS: Nm23 gene expression was
      compared in gastric carcinoma and normal gastric mucosa. Twenty-three gastric
      carcinomas were graded for differentiation as either well, moderately or poorly
      differentiated. Metastatic deposits from seven of the cases were also examined,
      along with 10 samples of normal gastric mucosa. Specimens were incubated with a
      murine monoclonal antibody against the protein product of Nm23, and examined by
      immunohistochemical staining. A semiquantitative immunostaining index was used.
      RESULTS: All normal mucosa showed moderate to strong staining; 8 of 15 poorly
      differentiated carcinomas showed absent or weak staining; 1 of 6 moderately
      differentiated carcinomas stained weakly. Both well-differentiated carcinomas
      stained strongly; 1 of 7 metastatic deposits stained weakly. The difference in
      Nm23 expression between normal mucosa and carcinomas was statistically
      significant (P=0.024). However, there was no statistically significant difference
      between the three grades of carcinomas (P=0.51), or between primary and
      metastatic tumour (P=0.25, all by Chi-squared test). CONCLUSIONS: These results
      suggest that Nm23 may have a role in gastric carcinoma pathogenesis, but do not
      show a correlation with metastasis. A larger study, involving detailed clinical
      staging and follow-up, may be of benefit.

PMID- 9563445
TI  - Latex allergy in non-spina bifida patients: unfamiliar intra-operative
      anaphylaxis.
AB  - BACKGROUND: The medical literature has described the prevalence of latex allergy
      in the spina bifida population and its implications for surgical intervention. We
      report three cases of severe and unexpected intra-operative anaphylaxis secondary
      to latex exposure in non-spina bifida patients. METHODS: A retrospective review
      of case notes identified three non-spina bifida patients who suffered intra
      operative anaphylaxis due to latex allergy. Personal and telephone interview and
      patient chart review was performed to detail a past history of multiple latex
      exposure, atopy, the anaphylaxis event and the postoperative outcome. RESULTS:
      Three non-spina bifida patients are described. One suffered a cardiopulmonary
      arrest, the remaining two patients had severe vascular hypotension and airway
      resistance that was only relieved after administration of vasoconstrictors and
      bronchodilators. Postoperatively, all three tested strongly positive to latex
      allergen testing. Each patient had a history of multiple surgical latex exposure
      and specific allergies or allergic-type symptoms pre-operatively. CONCLUSION: We
      believe that the predictors of a severe allergic reaction to latex with surgical
      exposure in non-spina bifida patients may be similar to those predictors known in
      the spina bifida population. Identification of such at-risk patients will reduce
      the risk of significant intra-operative morbidity and possible mortality by the
      introduction of a latex-free operating environment.

PMID- 9563446
TI  - Laparoscopic biliary injury: more than a learning curve problem.
AB  - BACKGROUND: The increase in the incidence of iatrogenic injury to the
      extrahepatic biliary tree that has been documented since the introduction of
      laparoscopic cholecystectomy (LC) has been explained as a 'learning curve'
      problem. The early New Zealand experience has been published and the present
      study was undertaken to determine whether there had been any change in the
      incidence, nature and management of laparoscopic biliary injuries (LBI) after
      further experience with LC. METHODS: A nationwide audit was undertaken in 1995 by
      two confidential postal questionnaires: to all active general surgeons (n=184,
      response rate 60%), and to all endoscopists performing endoscopic retrograde
      cholangiopancreatography (ERCP) (n=18, response rate 100%). RESULTS: The total
      number of LBI was 21, compared with 41 for 1991-92. The site and nature of the
      injuries were similar for the two survey periods. More of the injuries appeared
      to be diagnosed after the operation and prior to discharge (25% vs 47%).
      Calculating the national incidence of LBI was not possible without complete
      reporting, but in the subset of surgeons responsible for the LBI there was no
      apparent decrease in the incidence of all LBI (2.8% vs 2.9%), those requiring
      active re-intervention (2.4% vs 2.7%) and major duct injury (1.1% vs 0.7%),
      despite a significant increase in the surgeons' prior experience with LC (20% vs
      61% of surgeons had performed more than 100 LC). There were some concerning
      trends in management: a less frequent use of ERCP in patients with LBI diagnosed
      after surgery (76% vs 65%) and a higher proportion of patients with minor
      injuries managed by re-operation (26% vs 50%). CONCLUSIONS: The present study
      indicates that iatrogenic biliary injury is a persistent problem in New Zealand,
      despite increasing experience with LC, and suggests the need for more intensive
      scrutiny of operative technique and training. There is scope to manage more
      patients with minor duct injuries conservatively.

PMID- 9563447
TI  - Association of obesity, gender, age and occupation with carpal tunnel syndrome.
AB  - BACKGROUND: The present study determines the association of obesity, gender, age
      and occupation in patients with carpal tunnel syndrome (CTS) in a New Zealand
      population. METHODS: Analysis of questionnaires and clinical review of patients
      who had undergone surgical decompression of the median nerve in the carpal
      tunnel. RESULTS: The age and gender distribution of 655 hands (512 patients) that
      had undergone carpal tunnel release (CTR) were compared with the age and gender
      distribution of the New Zealand population. The results indicate that the 3-year
      period prevalence of CTS in females is more than double that in males.
      Proportionally there were more patients over age 55 than in the general
      population. The findings also indicate that, proportionally, six times the number
      of females who worked in moderate manual work underwent CTR compared with the
      general female population and proportionally twice the number of males who worked
      in heavy office/clerical work underwent CTR compared with the general male
      population. It was also found that CTR patients are twice as likely to be
      overweight (body mass index [BMI] > 25) than the general population and female
      patients are twice as likely to be obese (BMI > 30) than the general population.
      CONCLUSIONS: Carpal tunnel syndrome is more than twice as common in females as it
      is in males, and patients aged more than 55 years are more likely to suffer from
      CTS. Females with CTS are more likely to work in moderate manual work and males
      with CTS are more likely to work in heavy office/clerical work. Obesity and CTS
      are related statistically.

PMID- 9563448
TI  - Huckstep intramedullary nailing for non-union of humeral shaft fractures.
AB  - BACKGROUND: Various techniques of internal fixation for non-union of humeral
      shaft fractures have been attempted, leading to union rates of between 50 and 90%
      with persisting non-union causing pain and disability. Some of these techniques
      have led to shoulder and elbow dysfunction. METHODS: Eight patients treated with
      Huckstep nail fixation for humeral shaft non-union were reviewed and the rate of
      union was determined. Elbow and shoulder function were assessed as well as the
      presence of pain or disability. RESULTS: Union was achieved in seven of the eight
      patients (87.5%). Four patients had occasional mild pain after union. All
      patients achieved good arm function. Average shoulder abduction was 157 degrees
      and flexion 151 degrees excluding one patient with antecedent advanced
      osteoarthrosis of the gleno-humeral joint. No patient experienced any permanent
      neurological deficit. CONCLUSIONS: Huckstep nail fixation achieved union rates
      comparable to or higher than the other techniques of internal fixation for non
      union of humeral shaft fractures. Unlike the various methods of closed nailing,
      Huckstep nail fixation is not associated with shoulder and elbow dysfunction. It
      should be considered as a therapeutic option in humeral shaft fracture and non
      union, especially where the fracture site needs to be opened.

PMID- 9563449
TI  - The Mitrofanoff procedure in paediatric urinary tract reconstruction.
AB  - BACKGROUND: Urinary tract reconstruction is required in many congenital and some
      acquired urological conditions in childhood. The majority are managed by clean
      intermittent catheterization (CIC), for which purpose the appendix or other
      tubular structure may be used to provide a continent catheterizable abdominal
      stoma. METHODS: Between 1991 and 1996, 23 children underwent urinary tract
      reconstruction of varying complexity together with a continent diversion
      according to the Mitrofanoff principle. The appendix was used in 14 patients and
      the ureter in seven. Two patients had previously had an appendicectomy and the
      ureters were not suitable. One had a catheterizable channel made from an isolated
      segment of colon and the other had a detrusor tube constructed. RESULTS: Twelve
      patients with an appendix conduit, six with a ureteric conduit, and one with a
      colonic tube are continent, although the latter has had some problems with stomal
      stenosis. All manage CIC with comfort, the older children doing the procedure
      themselves. One appendix conduit has stomal incontinence and another was
      inadvertently divided during renal transplantation. The detrusor tube strictured
      and was removed. CONCLUSIONS: A continent abdominal stoma using the Mitrofanoff
      principle gives reliable results in children and is well tolerated. It should be
      considered in the management of children undergoing urinary tract reconstruction
      when CIC is necessary. The appendix is eminently suitable for this purpose but
      the ureter provides a satisfactory alternative in selected cases. When neither is
      available, alternative techniques for constructing a catheterizable continent
      channel may be considered.

PMID- 9563450
TI  - Tandem ureterocystoplasty.
AB  - BACKGROUND: Bladder augmentation may be undertaken by using various
      gastrointestinal segments but their use is associated with a multitude of well
      recognized complications. The mega-ureter has proven to be a satisfactory
      alternative; in patients with bilateral mega-ureters, both ureters may be used
      for this purpose. METHODS: Seventeen patients had augmentation
      ureterocystoplasty, including three in whom both distal ureters were used in
      tandem. The latter included two patients with neurogenic bladder and one with
      bladder exstrophy. RESULTS: Satisfactory augmentation was achieved in all
      patients undergoing tandem ureterocystoplasty. The neurogenic bladder patients
      are managed by urethral clean intermittent catheterization (CIC) and the
      exstrophy patient is managed by CIC of an appendicovesicostomy (Mitrofanoff). All
      are continent. CONCLUSIONS: The mega-ureter provides an excellent source of
      augmentation material in patients with small non-compliant bladders. In those
      with bilateral mega-ureters, consideration should be given to using both ureters
      in tandem to achieve the maximum possible bladder capacity.

PMID- 9563451
TI  - A clinical comparison of arterial and atrial repairs for transposition of the
      great arteries: early and midterm survival and functional results.
AB  - BACKGROUND: The early experience in correction of simple transposition of the
      great arteries (TGA) involved redirection of atrial inflow to re-establish
      systemic and pulmonary blood flow, the basis of the Senning and Mustard
      operations. Since 1984, however, the arterial switch operation (Jatene) has been
      increasingly used. It appears that with experience the peri-operative mortality
      rate for arterial repair is comparable to that for atrial repairs, while the late
      morbidity rates have generally favoured arterial repair, with sequelae such as
      obstruction of venous inflow, dysrhythmias, systemic atrioventricular valve
      dysfunction and impaired systemic ventricle function being more common following
      atrial repairs. METHODS: A retrospective review of patients surgically treated
      for TGA at the Prince Charles Hospital. RESULTS: Between April 1973 and July
      1994, 103 patients with simple TGA underwent surgical correction using one of
      three standard approaches currently advocated (arterial switch/Jatene, Senning or
      Mustard operations). Fifty-one Jatene, 31 Senning and 21 Mustard operations were
      performed. Associated procedures included closure of ventricular septal defect,
      right and left ventricular outflow tract resection and pulmonary artery band
      removal. The coronary artery anatomy was found to be suitable in all except two
      patients when the Jatene operation was planned; both these patients had a Senning
      procedure without mortality. There were nine peri-operative deaths (4 Jatene, 2
      Senning, 3 Mustard), and five late deaths (1 Jatene, 1 Senning, 3 Mustard).
      Follow-up was maintained to a mean time of 60.5 months (range, 9 days to 203
      months). In the Jatene group there were five anastomotic stenoses (all involving
      the neo-pulmonary artery), three cases of arrhythmias (two postoperative
      supraventricular tachycardia and one nodal rhythm) and two pulmonary valve
      stenoses. In the Senning group there were four anastomotic stenoses (three
      involving pulmonary vein and one causing superior vena cava (SVC) inlet
      obstruction) and four cases of arrhythmias (with one requiring permanent
      pacemaker insertion). In the Mustard group there were two cases of SVC
      obstruction and two permanent pacemaker insertions for bradycardia. CONCLUSIONS:
      These early and midterm results suggest that the arterial switch operation has
      comparable overall mortality to, and less morbidity than, the atrial repairs for
      TGA with the retention of left ventricle to systemic arterial connection, which
      may provide improved long-term results.

PMID- 9563452
TI  - Staging of oesophageal carcinoma by endoscopic ultrasound: preliminary
      experience.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is a relatively recent imaging modality
      that is capable of visualizing oesophageal tissue layers and para-oesophageal
      structures. Current pre-operative staging of oesophageal cancer is less than
      satisfactory, and a modality which may improve pre-operative staging, thus
      allowing a more rational approach to choice of treatment, may be a welcome
      addition to current techniques. The purpose of the present study was to evaluate
      the accuracy of EUS in the staging of oesophageal carcinoma in a consecutive
      cohort of patients. METHODS: Forty-three patients with oesophageal cancer were
      prospectively staged with EUS using the radial scanning Olympus EUM-3 echo
      endoscope. In the 28 patients who underwent surgery EUS staging was correlated
      with operative and histological findings to evaluate the EUS accuracy rate of
      assessing tumour depth (T stage), and the presence of nodal involvement (N stage)
      using internationally accepted TNM staging criteria. RESULTS: Endoscopic
      ultrasound accuracy rates for overall T-staging was 61% whereas that of N-staging
      was 75%. The overall TNM pathological staging was 75% accurate by EUS.
      CONCLUSIONS: Compared to published literature figures for oesophageal staging by
      computed tomography scanning (39-54%) these results demonstrate that EUS has a
      reasonable accuracy rate for staging. Endoscopic ultrasound may prove to be a
      useful additional modality in the management of oesophageal cancer.

PMID- 9563453
TI  - Laparoscopic underrunning of bleeding duodenal ulceration: a minimalist approach
      to therapy.
AB  - Surgical management of bleeding duodenal ulcer has traditionally included a
      procedure to reduce gastric acid production to enable ulcer healing and reduce
      the likelihood of rebleeding. The availability of intravenous proton pump
      inhibitors in the peri-operative period may promote rapid ulcer healing and as a
      component of anti-Helicobacter eradication therapy greatly reduces the incidence
      of ulcer recurrence. Using this approach, six patients with actively bleeding
      duodenal ulcer underwent laparoscopic duodenotomy and attempted suturing of the
      bleeding site. One patient required conversion to open surgery and subsequently
      re-bled at 60 h, necessitating a partial (Billroth II) gastrectomy. In the
      remaining five patients suture control of bleeding and luminal closure were
      completed laparoscopically without complications. Laparoscopic repair of acutely
      bleeding duodenal ulcers is technically feasible and had a low complication rate
      in this small series.

PMID- 9563454
TI  - Paediatric surgical training: a system that works.
AB  - BACKGROUND: Paediatric surgical trainees going through the system at the Royal
      Children's Hospital (RCH), Melbourne, have been impressed with the amount of time
      dedicated to postgraduate training compared with other institutions. They
      generally felt well prepared to sit for Fellowship examinations. We decided to
      look at the programme offered at the RCH and objectively assess the results.
      METHOD: A review was undertaken of the training system at the RCH. Opinions were
      sought from recent and current trainees and compared with trainees in other
      disciplines. Figures were obtained from the RACS Examinations Office with respect
      to pass rates at Fellowship examinations. RESULTS: The training programme is
      outlined in some detail. A total of 79% of candidates passed their FRACS in
      paediatric surgery while at the RCH since 1985, compared with 52% from all other
      institutions. CONCLUSIONS: A successful training programme requires a commitment
      to educate one's junior colleagues. Busy consultants can contribute actively by
      offering to teach and by encouraging their trainees to attend rounds and
      tutorials. The rewards are better-educated and well-rounded surgeons as well as,
      hopefully, a higher pass-rate at the Part 2 examination.

PMID- 9563455
TI  - The early history of tennis elbow: 1873 to the 1950s.

PMID- 9563456
TI  - A synopsis of radiation oncology in Australia, with particular reference to New
      South Wales.
AB  - The specialty of radiation oncology had its beginning in Australia in 1896
      following the discovery of X-rays by Roentgen. The new technology was eagerly
      embraced and the use of X-rays and radium for the treatment of cancer, even in
      the early 1900s, produced results which, although far from satisfactory by
      today's standards, resulted in cure and palliation of more superficial tumours.
      In the era immediately prior to World War II the specialty was regarded as having
      only a limited role to play in cancer management. The introduction of cobalt-60
      units and linear accelerators in the 1950s allowed for treatment of deep-seated
      tumours without the skin, bone and other complications of orthovoltage machines
      (deep X-rays). But the introduction of radiotherapy treatment into cancer care
      was blocked by other specialties anxious to preserve their own 'turf and by
      medical administrators who believed the counter-claims that either cancer was
      incurable or 'the cure for cancer was just around the comer' and it was therefore
      foolish to waste money on an expensive technology that had a limited future. With
      further developments in technology, modern radiotherapy is now a highly
      sophisticated treatment using sharply focused and deeply penetrating X-rays and
      electron beams. Specialized treatments, such as automated afterloading
      brachytherapy, total body irradiation, stereotactic radiosurgery and computerized
      3-D planning to improve dose distribution, are now widely available. The outcomes
      of cancer patients with radiotherapy have also improved considerably and organ
      preservation (e.g. in breast and larynx cancer) has resulted in improved quality
      of life. However, the specialty has only recently begun to expand in specialist
      numbers and profile. This is partly due to the lack of undergraduate training in
      cancer in general and radiotherapy in particular and also because understaffing
      has meant that radiation oncologists have occupied a purely service role (in the
      basement with their machines) rather than being an active part of the treatment
      'team'. As a consequence radiation oncology has not been projected as an
      important component in cancer management and as a challenging and fulfilling
      career option to medical students and new graduates. The failure to act on the
      (repeated) recommendations of the 42 reports, inquiries, etc. into radiation
      oncology in Australia since 1982 (in addition to many more at local level) would
      suggest that the 'message' has yet to be accepted by Health Departments and
      health administrators. As a result there has been a totally uncoordinated
      approach to provision of radiation oncology services. The restriction of services
      and specialist numbers and training posts has led to radiotherapy being
      underutilized and undervalued in the treatment of cancer, ultimately to the
      detriment of cancer patients.

PMID- 9563457
TI  - How accurate are references in The Australian and New Zealand Journal of Surgery?
      Comment.

PMID- 9563458
TI  - Mesenteric panniculitis: a mimic of malignancy.

PMID- 9563459
TI  - Pyourachus in an 8-year-old female.

PMID- 9563460
TI  - Osteochondroma of the axis: a unique case.

PMID- 9563461
TI  - Primary aortoduodenal fistula.

PMID- 9563462
TI  - Primary aortoduodenal fistulas with nine 'herald' bleeds.

PMID- 9563464
TI  - Frequent abnormalities of the putative tumor suppressor gene FHIT at 3p14.2 in
      pancreatic carcinoma cell lines.
AB  - The FHIT gene is localized on chromosome 3p14, a region including a tumor cell
      specific, commonly deleted region. To determine the role of the FHIT gene in
      pancreatic carcinogenesis, 14 pancreatic carcinoma cell lines were analyzed by
      reverse transcription-PCR and exon-specific PCR amplification of genomic DNA. The
      full-length FHIT transcript was lost in 70% of the pancreatic carcinoma cell
      lines analyzed, while 66% also revealed intragenic homozygous deletions of exons
      3, 4, and 5. Truncated FHIT transcripts lacking a variable number of exons most
      likely represented alternative splicing products. Fhit protein expression was
      dependent on a full-length FHIT transcript. The results suggest that the FHIT
      gene may be a target tumor suppressor gene involved in pancreatic carcinogenesis.

PMID- 9563465
TI  - Mutations at BRCA1: the medullary breast carcinoma revisited.
AB  - BRCA1-associated breast cancers (BRCA1-BCs) frequently harbor a high
      histoprognostic grade, p53 alterations, and estrogen receptor negativity.
      Although these parameters predict a poor outlook, the overall survival in BRCA1
      BCs is equivalent to or even better than that in sporadic cases. These features
      are reminiscent of what is observed for breast carcinoma of the medullary type, a
      high-grade tumor with a particular favorable course. To explore a possible
      relationship between this phenotype and BRCA1 mutations, we first compared 32
      BRCA1-BCs and 200 consecutive cases of breast cancer without familial history for
      the prevalence of typical medullary breast carcinoma (TMC) using the criteria
      given by Ridolfi et al. [R. Ridolfi et al, Cancer (Phila.), 40: 1365-1385, 1977].
      Second, we searched for BRCA1 mutations in a set of 18 cases of TMC, using
      denaturing gradient gel electrophoresis and Cleavase fragment length polymorphism
      scanning. Six of 32 (19%) BRCA1-BCs were of the TMC type, compared to 0 of 200
      controls (P < 0.0001). Among the 18 TMCs, 2 BRCA1 nonsense mutations were found.
      This corresponds to almost 7 times the contribution of BRCA1 mutations in the
      general population. Two additional missense mutations were identified. Together,
      these results suggest that, although TMC and BRCA1-BCs are not strictly
      coincidental, an important connection between the two populations does exist.

PMID- 9563466
TI  - p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene
      expression in response to genotoxic stress and tumor necrosis factor alpha.
AB  - The death receptor (DR) KILLER/DR5 gene has recently been identified as a
      doxorubicin-regulated transcript that was also induced by exogenous wild-type p53
      in p53-negative cells. KILLER/DR5 gene encodes a DR containing cell surface
      protein that is highly homologous to DR4, another DR of the tumor necrosis factor
      (TNF) receptor family. Both DR4 and KILLER/DR5 independently bind to their
      specific ligand TRAIL and engage the caspase cascade to induce apoptosis. TRID
      (also known as TRAIL-R3) is an antiapoptotic decoy receptor that lacks the
      cytoplasmic death domain and competes with KILLER/DR5 and DR4 for binding to
      TRAIL. In this study, we demonstrate that the DR KILLER/DR5 gene is regulated in
      a p53-dependent and -independent manner during genotoxic and nongenotoxic stress
      induced apoptosis. Just like other p53-regulated genes, ionizing radiation
      induction of KILLER/DR5 occurs in p53 wild-type cells, whereas methyl
      methanesulfonate regulation of KILLER/DR5 occurs in a p53-dependent and 
      independent manner. However, unlike other p53-regulated genes, KILLER/DR5 is not
      regulated following UV irradiation. TNF-alpha, a nongenotoxic cytokine, also
      induced the expression of KILLER/DR5 in a number of cancer cell lines,
      irrespective of p53 status. TNF-alpha did not alter the KILLER/DR5 mRNA
      stability, suggesting that the TNF-alpha regulation of KILLER/DRS expression
      appears transcriptional. We also provide evidence that KILLER/DR5 is regulated in
      a trigger and cell type-specific manner and that its induction by TNF-alpha, p53,
      or DNA damage is not the consequence of apoptosis induced by these agents. Unlike
      KILLER/DR5, none of the other KILLER/DR5 family members, including DR4, TRID, or
      the ligand TRAIL, displayed genotoxic stress or TNF-alpha regulation in a p53
      transcription-dependent manner. Thus, KILLER/DR5 appears a bona fide downstream
      target of p53 that is also regulated in a cell type-specific, trigger-dependent,
      and p53-independent manner.

PMID- 9563467
TI  - Lymphatic endothelium and Kaposi's sarcoma spindle cells detected by antibodies
      against the vascular endothelial growth factor receptor-3.
AB  - Lymphatic vessels have been difficult to study in detail in normal and tumor
      tissues because of the lack of molecular markers. Here, monoclonal antibodies
      against the extracellular domain of the vascular endothelial growth factor-C
      receptor that we have named VEGFR-3 were found to specifically stain endothelial
      cells of lymphatic vessels and vessels around tumors such as lymphoma and in situ
      breast carcinoma. Interestingly, the spindle cells of several cutaneous nodular
      AIDS-associated Kaposi's sarcomas and the endothelium around the nodules were
      also VEGFR-3 positive. The first specific molecular marker for the lymphatic
      endothelium should provide a useful tool for the analysis of lymphatic vessels in
      malignant tumors and their metastases and the cellular origin and differentiation
      of Kaposi's sarcomas.

PMID- 9563468
TI  - Benzo[a]pyrene diol epoxide-induced 3p21.3 aberrations and genetic predisposition
      to lung cancer.
AB  - 3p deletion, a common chromosome defect in lung cancer, occurs more frequently in
      the lung tumor tissues of smoking patients than it does in those of nonsmoking
      patients. This pilot study evaluated whether 3p aberrations induced by
      benzo[a]pyrene diol epoxide (BPDE), the metabolic product of benzo[a]pyrene, a
      constituent of tobacco smoke, were more common in the peripheral blood
      lymphocytes of 40 lung cancer patients than they were in those of 54 matched
      controls. Our hypothesis was that 3p sensitivity to BPDE reflects the
      susceptibility of a specific locus to damage from carcinogens in tobacco smoke.
      BPDE-induced chromosome 3p21.3 aberrations were significantly more frequent in
      cases (34.1 per 1000) than they were in controls (22.1 per 1000; P < 0.0001).
      However, no such difference was observed for 6q27, a control locus. Using the
      median value in the controls (20 per 1000) as a cutoff point to classify BPDE
      induced sensitivity at 3p21.3 and after adjustment by age, sex, ethnicity, and
      smoking status, 3p BPDE sensitivity was associated with an elevated risk of 14.1
      (95% confidence interval: 3.5, 56.2) for lung cancer. There was also a dose
      response relationship between the degree of BPDE sensitivity at 3p21.3 and
      increased risk for lung cancer. Therefore, 3p may be a molecular target for BPDE
      damage in lung cancer cases.

PMID- 9563469
TI  - Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in
      cancer cells.
AB  - Taxoids and other microtubule-damaging drugs are known to induce Bcl2
      phosphorylation at the G2-M phase of the cell cycle, with concomitant apoptosis
      in malignant cells derived from a variety of human malignancies, including
      leukemia, lymphoma, and breast and prostate cancer. We have investigated the
      ability of another antineoplastic drug, dolastatin 10, in inducing Bcl2
      phosphorylation and apoptosis. We also investigated the effects of a phosphatase
      inhibitor okadaic acid in the regulation of Bcl2 phosphorylation, cell cycle
      arrest, and programmed cell death. Moreover, site-directed mutagenesis studies
      were performed to determine the specific serine residue(s) responsible for drug
      induced Bcl2 phosphorylation. Our results indicate that these antimicrotubule
      agents or okadaic acid can induce posttranslational modification
      (phosphorylation) of Bcl2 protein at multiple serine residues. Interestingly,
      mutation of a serine residue at position 70 to alanine can significantly decrease
      drug-induced posttranslational modification (phosphorylation) of Bcl2 protein.
      Apparently, Ser70 seems to be a critical site for drug-induced posttranslational
      modification (phosphorylation) of the Bcl2 protein.

PMID- 9563470
TI  - Association of elevated mutagenesis in the spleen with genetic susceptibility to
      induced plasmacytoma development in mice.
AB  - Using the phage lambdaLIZ-based transgenic in vivo mutagenesis assay, mean mutant
      rates were determined in the spleen of mice exposed to sustained oxidative stress
      and were found to be increased approximately 3-fold in plasmacytoma-susceptible
      BALB/c and C.D2-Idh1-Pep3 mice, but not in plasmacytoma-resistant DBA/2N mice.
      This finding suggests a correlation between the genetic susceptibility to
      inflammation-induced peritoneal plasmacytomagenesis and the phenotype of
      increased mutagenesis in lymphoid tissues, raising the possibility that
      plasmacytoma resistance genes may inhibit tumor development by minimizing
      oxidative mutagenesis in B cells.

PMID- 9563471
TI  - Association of prostate cancer with vitamin D receptor haplotypes in African
      Americans.
AB  - In previous studies, allelic variation in the 3' end of the vitamin D receptor
      gene was associated with increased risk of prostate cancer in white men. Several
      polymorphisms, including a BsmI restriction site and a poly(A) microsatellite,
      can be used interchangeably to mark the unidentified locus in whites. In African
      Americans, however, these markers are not interchangeable, due to weaker linkage
      disequilibrium in this genomic region in this population. Here, we genotyped both
      the BsmI and poly(A) markers for 151 African-American prostate cancer cases (102
      localized and 49 advanced) and 174 African-American male controls from a large
      epidemiological cohort. A direct haplotyping procedure was devised to determine
      BsmI/poly(A) haplotypes for double heterozygotes so that haplotypes could be used
      as allelic markers in standard logistic regression analyses. Using BsmI alone, b
      alleles were associated with a 2-fold decrease in risk of advanced prostate
      cancer. The association was, however, confined to haplotypes carrying a long (L)
      allele of the poly(A) microsatellite. BL and bL haplotypes were associated with
      increased and decreased risk, respectively, whereas neither BS nor bS haplotypes
      were associated with prostate cancer risk. An allelic variant that confers
      increased risk of advanced prostate cancer appears to be associated with the
      BsmI/poly(A) BL haplotype in African-Americans.

PMID- 9563472
TI  - Cathepsin L2, a novel human cysteine proteinase produced by breast and colorectal
      carcinomas.
AB  - We have identified and cloned a new member of the papain family of cysteine
      proteinases from a human brain cDNA library. The isolated cDNA codes for a
      polypeptide of 334 amino acids that exhibits all of the structural features
      characteristic of cysteine proteinases, including the active site cysteine
      residue essential for peptide hydrolysis. Pairwise comparisons of this amino acid
      sequence with the remaining human cysteine proteinases identified to date showed
      a high percentage of identity (78%) with cathepsin L; the percentage of identity
      with all other members of the family was much lower (<40%). On the basis of these
      structural characteristics, we have tentatively called this novel protein
      cathepsin L2. The cDNA encoding the mature cathepsin L2 was expressed in
      Escherichia coli, and after purification, the recombinant protein was able to
      degrade the synthetic peptide benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido
      4-methylcoumarin, which is commonly used as a substrate for cysteine proteinases.
      Cathepsin L2 proteolytic activity on this substrate was abolished by trans
      epoxysuccinyl-L-leucylamido-(4-guanidino)butane, an inhibitor of cysteine
      proteinases, thus providing additional evidence that the isolated cDNA encodes a
      functional cysteine proteinase. Northern blot analysis of polyadenylated RNAs
      isolated from a variety of human tissues demonstrated that cathepsin L2 is
      predominantly expressed in the thymus and testis. This finding is in marked
      contrast with the wide tissue distribution of most cysteine proteinases
      characterized to date, including cathepsin L, and suggests that cathepsin L2 may
      play a specialized role in the thymus and testis. Expression analysis of
      cathepsin L2 in human tumors revealed a widespread expression in colorectal and
      breast carcinomas but not in normal colon or mammary gland or in peritumoral
      tissues. Cathepsin L2 was also expressed by colorectal and breast cancer cell
      lines as well as by some tumors of diverse origin, including ovarian and renal
      carcinomas. These results open the possibility that this novel enzyme may be
      involved in tumor processes, as already reported for other cysteine proteinases,
      including cathepsin L.

PMID- 9563473
TI  - Increased beta-actin expression in an invasive moloney sarcoma virus-transformed
      MDCK cell variant concentrates to the tips of multiple pseudopodia.
AB  - An invasive variant of Moloney sarcoma virus-transformed MDCK cells (MSV-MDCK
      INV), which was isolated by the repeated selection of cells that successfully
      traversed a Matrigel-coated filter, exhibits increased motile ability and
      presents an elongated cell shape and numerous pseudopodia. Although stress fibers
      are present in both MDCK and MSV-MDCK cells, MSV-MDCK-INV cells contain no stress
      fibers and exhibit a dense concentration of actin at the tips of pseudopodia.
      Relative to both MDCK and MSV-MDCK cells, the MSV-MDCK-INV cells exhibit
      increased expression of beta-actin and redistribution of beta-actin to the tips
      of pseudopodia. These actin concentrations are enriched in both F- and G-actin
      and, thus, represent dynamic regions of actin cytoskeleton remodeling. The
      acquisition of invasive properties by epithelial transformants is, therefore,
      associated with the increased expression of beta-actin and its concentration in
      actin-rich domains, which may drive pseudopodial extension and facilitate tumor
      cell invasion.

PMID- 9563474
TI  - High-intensity Raf signals convert mitotic cell cycling into cellular growth.
AB  - The selection of NIH 3T3 cells expressing a hydroxytamoxifen-inducible c-Raf-1
      estrogen receptor fusion protein (c-Raf-1-BxB-ER) in the absence or presence of
      the inducer results in dramatic differences in the expression levels of the
      fusion protein. Hydroxytamoxifen-mediated constitutive activation of the Raf
      signal favors the selection of cells expressing low levels of c-Raf-1-BxB-ER.
      Cells selected in the absence of hydroxytamoxifen express up to 20 times higher
      levels of the inducible Raf kinase. Activation of the oncogenic Raf kinase in
      cells expressing low levels leads to a weak activation of the Raf/Mek/Erk cascade
      and the induction of S phase in confluent cells. The activation of cells
      expressing high levels of the kinase leads to a strong persistent signal and
      inhibits DNA synthesis and mitosis in proliferating cells. The inhibition of DNA
      synthesis and cell division is presumably due to the elevated expression of the
      cyclin-dependent kinase inhibitor p21cip1, similar to cells exposed to ionizing
      radiation. Despite the inhibition of DNA synthesis and mitosis, the constitutive
      activity of the Raf signaling pathway is still able to initiate cell growth.
      Activation of the high-intensity Raf signal in arrested serum-starved cells
      induces cell growth up to a size corresponding to that of M-phase cells in the
      absence of DNA synthesis. High-intensity Raf signals in proliferating cells
      consistently lead to an accumulation of cells with the size of M-phase cells and
      the DNA content of G1 cells or G2-M-phase cells. Therefore, the activation of Raf
      kinase is sufficient to drive cell growth, even in the presence of high levels of
      the cyclin-dependent kinase inhibitor p21cip1.

PMID- 9563475
TI  - Protein kinase C activation increases transepithelial transport of biologically
      active insulin.
AB  - Protein kinase C activation leads to tight junctional leakiness and,
      consequently, to increased transepithelial (paracellular) solute flux across
      epithelial barriers. This leakiness is shown here to result in as much as a 20
      fold increase in the transepithelial flux of insulin. Using an
      epithelial/fibroblast coculture model, this transepithelially transported insulin
      is shown to be biologically active. The 3T3 fibroblasts situated on one side of
      the epithelial barrier exhibited increased insulin binding and resulting DNA
      synthesis when the epithelial junctions were made leaky to insulin on the
      opposite side of the epithelial barrier. The dramatically enhanced permeability
      of macromolecules across epithelial cell layers undergoing protein kinase C
      activation may play a significant role in epithelial cancer, immunology, and drug
      delivery.

PMID- 9563476
TI  - E2F1 messenger RNA is destabilized in response to a growth inhibitor in normal
      human keratinocytes but not in a squamous carcinoma cell line.
AB  - Keratinocyte growth arrest is characterized by a reduction in the activity and
      expression of E2F1. Here, we examine the role posttranscriptional processing
      plays in the down-regulation of E2F1 during keratinocyte growth arrest. E2F1 mRNA
      levels were undetectable within 8 h of exposure to the protein kinase C
      activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Assays of transcript
      stability indicated that, in untreated keratinocytes, the t 1/2 of E2F1 mRNA was
      6.1 h and, in TPA-treated cells, it was 1.7 h. This destabilization was protein
      synthesis-dependent. In contrast, a growth inhibitor-resistant carcinoma cell
      line, SCC25, had a very stable E2F1 half-life that was only moderately reduced
      following TPA treatment. These data demonstrate that the initiation of
      keratinocyte growth arrest is associated with a rapid destabilization of E2F1
      mRNA. These data are consistent with the proposition that inactivation of the
      posttranscriptional processing of important growth regulatory genes (e.g., E2F1)
      may contribute to neoplasia.

PMID- 9563477
TI  - The mammalian ribonucleotide reductase R2 component cooperates with a variety of
      oncogenes in mechanisms of cellular transformation.
AB  - Ribonucleotide reductase, which is composed of the two protein components R1 and
      R2, is a highly regulated enzyme activity that is essential for DNA synthesis and
      repair. Recent studies have shown that elevated expression of the rate-limiting
      R2 component increases Raf-1 protein activation and mitogen-activated protein
      kinase activity and acts as a novel malignancy determinant in cooperation with H
      ras and rac-1. We show that R2 cooperation in cellular transformation extends to
      a variety of oncogenes with different functions and cellular locations. Anchorage
      independent growth of cells transformed with v-fms, v-src, A-raf, v-fes, c-myc,
      and ornithine decarboxylase was markedly enhanced when the R2 component of
      ribonucleotide reductase was overexpressed. In addition, we observed that
      elevated R2 expression conferred on c-myc-transformed NIH 3T3 cells an increased
      tumorigenic potential in immunoincompetent mice. Taken together, these
      observations demonstrate that the R2 protein is not only a rate-limiting
      component for ribonucleotide reduction but that it is also capable of acting in
      cooperation with a variety of oncogenes to determine transformation and
      tumorigenic potential.

PMID- 9563479
TI  - Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue
      carcinogenesis in the rat.
AB  - The incidence of tongue carcinomas (TCs) induced by oral administration of 4
      nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA)
      strain showed a much higher susceptibility to large mass-forming infiltrative TCs
      than did the Wistar-Furth (WF) strain. Our previous study (M. Kitano et al, Jpn.
      J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains
      postulated a dominant susceptibility gene in DA and a dominant resistance gene in
      WF rats. The present study mapped these loci by analyzing the backcrosses to each
      parent with simple sequence repeat polymorphisms. Five quantitative parameters
      were analyzed: (a) the number of TCs > 5 mm in diameter; (b) the total number of
      TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number
      of non-TC cancers per rat; and (e) and the number of cancers of any site per rat.
      All of these parameters were closely correlated (P < 0.0001). DA rats had a
      semidominant gene (Stc1) favoring the development of 4-nitroquinoline 1-oxide
      induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was
      observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of
      5.72 for the number of large TCs and 6.08 for the DTCmax. On the other hand, WF
      rats had a semidominant gene (Rtc1) mapped between D1Mit1 and D1Mit3,
      approximately 20 cM from D1Mit1, with a peak lod score of 3.30 for both the
      number of large TCs and the DTCmax. The main effect of Rtc1 seemed to be to
      reduce the size of the TCs. The action of these genes was dose dependent and
      cooperative. The final incidence of TC in DA, WF, F1, and backcross rats seemed
      to be explained by combinations of genotype at these two loci. Possible candidate
      genes for Stc1 and Rtc1 are discussed.

PMID- 9563478
TI  - Polyamines regulate expression of the neoplastic phenotype in mouse skin.
AB  - Elevated polyamine levels are characteristic of many types of neoplastic cells
      and tissues. We demonstrate that in transgenic mice overexpressing ornithine
      decarboxylase in skin, changes in tissue polyamine levels, particularly
      putrescine, control the development and maintenance of the neoplastic phenotype.
      A specific inhibitor of the transgene, alpha-difluoromethylornithine (DFMO),
      reversibly blocked the appearance of squamous papillomas after carcinogen
      treatment. Furthermore, treatment of papilloma-bearing mice with DFMO caused
      rapid tumor regression, also in a reversible manner. Although the rate of
      apoptosis in papillomas was unaffected by acute DFMO treatment, tumor cell
      proliferation was rapidly decreased after drug treatment. Conversely,
      proliferation of normal epidermal keratinocytes was unaffected by DFMO treatment.
      The regulatory polyamine in this model appears to be putrescine, the immediate
      product of ornithine decarboxylase. These results demonstrate that elevated
      polyamine levels are required for both the development and maintenance of the
      neoplastic phenotype in skin.

PMID- 9563480
TI  - Mechanism of the paradoxical, inhibitory effect of phenobarbital on
      hepatocarcinogenesis initiated in infant B6C3F1 mice with diethylnitrosamine.
AB  - Phenobarbital (PB), a classical rodent hepatopromoter, remarkably enhances
      hepatocarcinogenesis initiated by diethylnitrosamine (DEN) in adult B6C3F1 mice.
      However, it is also known to strongly inhibit liver tumor development in the
      B6C3F1 mice initiated with DEN in their infancy. The present study aimed to
      elucidate the unknown biological mechanisms for this paradoxical, inhibitory
      effect of PB on B6C3F1 mouse hepatocarcinogenesis. Male 12-day-old infant B6C3F1
      mice were injected i.p. with DEN and, at 6 weeks of age, divided into PB-treated
      (PB+ group) and untreated (PB- group) animals. At 24 weeks, PB treatment was
      ceased for half of the PB+ animals (PB+/- group) and started for half of the PB-
      animals (PB-/+ group). Finally, all mice were sacrificed at 36 weeks and examined
      for the development of liver tumors. The mean multiplicity of gross tumors in the
      PB+ group was only one-fifteenth of that for the PB- group. PB-/+ animals
      developed fewer than half of the tumors found in PB- mice, indicating that the PB
      effect depends solely on the treatment duration, rather than the animal age. The
      effect was proven to be reversible, because the mean tumor multiplicity for the
      PB+/- group was seven times larger than that for the PB+ group. Stereological
      analysis revealed the mean volume of hepatocellular proliferative lesions in the
      PB- animals to be 7.7- and 4.1-fold the values for the PB+ and PB-/+ groups,
      respectively. The mean proliferating cell nuclear antigen-labeling indices for
      hepatocellular adenomas in PB+ and PB-/+ animals were also one-third of that for
      tumors in PB- animals, whereas no significant differences were observed with
      regard to the mean apoptotic index. In conclusion, the inhibitory effect of PB
      seemed to be primarily caused by the suppression of tumor cell proliferation.
      Irrespective of the group, most lesions observed were basophilic hepatocellular
      adenomas or foci, positive for Bcl-2 oncoprotein. They were thus distinct from
      the eosinophilic Bcl-2- lesions that predominate with PB promotion after the
      initiation of adult B6C3F1 mice. This age-dependent nature of initiation,
      together with the differential responses of Bcl-2+ and Bcl-2- lesions, may be
      responsible for the apparently contradictory outcomes of PB treatment in infant
      and adult B6C3F1 mice.

PMID- 9563481
TI  - Expression of insulin-like growth factor-binding protein 6 complementary DNA
      alters neuroblastoma cell growth.
AB  - Insulin-like growth factors I and II (IGF-I and IGF-II) are actively involved in
      neuroblastoma cell growth. In all biological fluids, they are noncovalently bound
      to high-affinity binding proteins. At least six species of these IGF-binding
      proteins (IGFBPs) have been identified, but their precise roles remain unclear.
      One of them, IGFBP-6, is produced by neuroblastoma cells in culture under certain
      experimental conditions and seems to be associated with the arrest of cell
      growth. We stably transfected IGR-N-91 and SK-N-SH neuroblastoma cells with an
      expression vector comprising IGFBP-6 cDNA, whose expression was placed under the
      control of the constitutive and ubiquitous cytomegalovirus promoter. Analyses of
      the cell cycle (flux cytofluorometry), mitogenic activity (radiolabeled thymidine
      incorporation), and the number of viable cells (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide test) showed that the mitogenic effects of serum, IGF
      I, IGF-II, and des (1-3) IGF-I, a truncated IGF-I analogue with no affinity for
      IGFBP-6, were depressed in both transfected cell lines. With s.c. injection of
      transfected IGR-N-91 cells into nude mice, tumors developed in only 50-70% of
      cases, 1 or 2 weeks after those in controls, and were 60-90% smaller. Our
      findings show that IGFBP-6 influences neuroblastoma cell growth, both in vitro
      and in experimental xenograft development.

PMID- 9563482
TI  - An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55
      kDa tumor necrosis factor (TNF) receptor gene transfection and mutein TNF
      administration.
AB  - Intratumoral injection of recombinant human tumor necrosis factor (TNF) for
      inoperable pancreatic cancer has shown some efficacy in suppressing tumor growth
      or decreasing tumor markers. However, complete regression has not yet been
      achieved, possibly due to a lack of TNF receptors on tumor cells or an abundance
      of intracellular resistance factors. Recently, two distinct types of TNF
      receptors, R55 and R75, were identified, which are responsible for signaling of
      cytotoxicity and of proinflammation, respectively. In this study, a novel type of
      suicide gene therapy is proposed that is based on transfection of the R55 gene
      into human pancreatic cancer cells (AsPC-1 and PANC-1) and subsequent
      administration of TNF. The transfectants from both cell lines showed higher TNF
      susceptibility than their parental cells. In vivo tumor formation of an AsPC-1
      clone (clone 10) inoculated in nude mice was substantially suppressed by
      administration of TNF. For practical use of this strategy, however, the adverse
      effects of TNF may become an obstacle. We previously produced mutein TNF 471,
      which had a higher affinity for R55, superior antitumor activity, and fewer
      adverse effects. This mutein TNF 471 manifested greater antitumor activity
      against clone 10. Because the R55 receptor is known to be involved in
      augmentation of cellular immunity by TNF, mutein TNF 471 is also expected to be
      highly potent in this function. In fact, the mutein TNF 471 induced higher
      splenic natural killer cell activity in nude mice inoculated with clone 10 than
      did native TNF. This property of augumenting cellular responses may be
      advantageous in the eradication of viable tumor cells left untransfected in
      practical gene therapy regimens in which 100% transfection of the R55 gene into
      tumors is not feasible. Thus, gene therapy combining transfection of the TNF-R55
      gene with administration of mutein TNF 471 may provide a new modality for the
      treatment of pancreatic cancer.

PMID- 9563483
TI  - Enrichment of the more hydrophilic bile acid ursodeoxycholic acid in the fecal
      water-soluble fraction after feeding to rats with colon polyps.
AB  - We recently showed that feeding the cytoprotective bile acid ursodeoxycholic acid
      (UDCA) to rats resulted in significant reduction in polyps and especially
      cancers, both in number and size (D. L. Earnest et al., Cancer Res., 54: 5071
      5074, 1994). Because fecal secondary bile acids [particularly deoxycholic acid
      (DCA)] are considered to promote formation of colon adenomas and cancer, we have
      now attempted to find a relationship between polyp reduction and fecal secondary
      bile acids after feeding UDCA to these rats. We examined the fecal bile acids in
      rats with polyps and compared them with fecal bile acids in control rats and also
      determined the bile acid composition in fecal aqueous phase, which is in direct
      contact with the colon epithelium and may be physiologically more active.
      Treatment with azoxymethane did not significantly alter fecal bile acid
      composition in the rats. Cholic acid feeding resulted in greatly increased
      proportions of DCA (82% of total bile acids versus 18% in control rats). On the
      other hand, UDCA feeding significantly reduced the proportion of fecal DCA (2% in
      control rats fed UDCA and 3% in rats also treated with azoxymethane). In control
      rats, 96% of the bile acids were present in the water-insoluble fraction and 4%
      in the water-soluble fraction. The major insoluble bile acids included DCA and
      hyodeoxycholic acid (73% of total bile acids). In contrast, the muricholic acids
      were concentrated in the soluble fraction (37%). When 0.4% UDCA was added to the
      diet, lithocholic acid increased in the insoluble fraction (40 versus 1%), but
      the hydrophilic UDCA and muricholic acids were enriched in the water-soluble
      fraction (37 and 43%, respectively). Thus, the hydrophobic bile acids were
      distributed predominantly in the water-insoluble fraction, whereas the
      hydrophilic bile acids were distributed preferentially in the water-soluble
      fraction. These data suggest that UDCA may prevent colon tumors and polyps by
      countering the toxic effect of DCA and enhancing the possible cytoprotective
      effects of UDCA and muricholic acids in the water-soluble fraction in the feces
      of rat.

PMID- 9563485
TI  - Interleukin 15 protects against toxicity and potentiates antitumor activity of 5
      fluorouracil alone and in combination with leucovorin in rats bearing colorectal
      cancer.
AB  - 5-Fluorouracil (FUra) modulated by leucovorin (LV) is active in the treatment of
      colorectal cancer. Diarrhea and stomatitis are the most common dose-limiting
      toxicities. We have developed a model system in rats bearing a transplantable
      colon carcinoma sensitive to FUra therapy with dose-limiting toxicity profiles
      similar to what is observed in patients treated with either daily or weekly
      schedules of FUra plus LV. Interleukin 15 (IL-15), a cytokine that shares many
      biological activities with IL-2, was used at different doses (25, 100, and 400
      microg/kg) and schedules (three doses before a single dose of FUra, FUra/LV daily
      x 5, or before each week of FUra/LV weekly x 4, or three doses before a single
      dose of FUra or FUra/LV daily x 5, then twice daily x 5 for a total of 11 doses)
      to evaluate its role in the modulation of the therapeutic selectivity of FUra
      alone and modulated by LV. IL-15 induced a dramatic decrease in chemotherapy
      induced gastrointestinal toxicities, significant potentiation of antitumor
      activity, and an increased therapeutic index of FUra administered on single dose,
      daily x 5 and weekly x 4 schedules. In contrast, IL-2 (400 microg/kg)
      significantly potentiated the toxicity of FUra administered as a single i.v.
      push, with minimal potentiation of the antitumor activity. Taken together, the
      results clearly demonstrated the ability of IL-15, but not IL-2, to provide
      significant improvement of the therapeutic index of FUra alone and in combination
      with LV. The clinical relevance of the results obtained in this model system
      needs to be confirmed.

PMID- 9563484
TI  - Regional pharmacokinetics of 5-fluorouracil in dogs: role of the liver,
      gastrointestinal tract, and lungs.
AB  - The purpose of this study was to determine the presence and extent of pulmonary
      elimination for 5-fluorouracil (FUra). A secondary aim was to characterize the
      relative importance of the liver, gastrointestinal tract, splanchnic region, and
      lungs toward the overall elimination of FUra. A total of 10 mixed-breed male and
      female dogs were used in these acute studies in which FUra was administered
      through a cephalic vein. Six dogs were studied at sequentially escalated dose
      rates of 0.125, 0.250, 0.500, 0.750, and 1.00 micromol/min/kg (8-fold range);
      four dogs were studied at sequentially escalated dose rates of 0.0625, 0.250,
      0.750, 1.50, and 2.00 micromol/min/kg (32-fold range). Each infusion lasted 2 h,
      at which time steady-state plasma concentrations were obtained (i.e., portal
      vein, carotid artery, hepatic vein, and pulmonary artery), perfusion rates were
      measured (hepatic artery, portal vein, and cardiac output), and pharmacokinetic
      parameters were directly assessed. Pulmonary elimination of FUra was conclusively
      demonstrated. Although only 17% of the drug was extracted by the lungs at the
      lowest dose rate, pulmonary clearance (16.0 ml/min/kg) was on the order of
      splanchnic clearance (13.5 ml/min/kg), or larger. As the dose rate increased,
      pulmonary clearance was more easily saturated than splanchnic clearance. Thus, it
      appears that at increasing dose rates, the splanchnic region becomes a more
      significant pathway, whereas the lungs have a reduced role in the overall
      elimination of FUra.

PMID- 9563486
TI  - Differential T helper cell responses to human papillomavirus type 16 E7 related
      to viral clearance or persistence in patients with cervical neoplasia: a
      longitudinal study.
AB  - T-cell-mediated immune responses against oncogenic human papillomaviruses (HPVs)
      are believed to play a role in the prevention of cervical carcinogenesis. The in
      vitro production of interleukin 2 by CD4+ T helper (Th) cells in response to
      overlapping 20-mer peptides covering the HPV-16 E7 oncoprotein sequence was
      determined in 72 women with cytological evidence of premalignant cervical
      intraepithelial neoplasia (CIN) who participated in a nonintervention follow-up
      (FU) study. In addition, 15 HPV-16 + cervical carcinoma patients were tested.
      Positive Th cell reactivity was restricted to patients infected by HPV-16 and
      related types and showed a strong association with viral persistence and disease
      progression, as evidenced by the high frequency of positive responders among
      women with persistent HPV-16 infections who ended FU with high-grade CIN III
      lesions [14 of 15 (93%)]. Women with cervical carcinoma showed responses at a
      significantly reduced rate [7 of 15 (47%); P = 0.014]. Over the FU period (10-34
      months), the level of E7-induced interleukin 2 production from the lymphocytes of
      CIN patients who had cleared HPV-16 infection showed an inverse correlation with
      time relative to the last positive HPV DNA test, with 8 of 13 of these patients
      showing positive responses after clearance. By contrast, among women with
      persistent HPV-16 infections and developing CIN III lesions (n = 8), there was a
      rise in Th cell activity over the course of FU. The majority of women responded
      to an immunogenic region in the carboxyl terminus of the E7 protein (amino acids
      67-98). The observed HPV-16 E7-specific Th cell responses may develop as a
      consequence of increased antigen availability resulting either from clearance or
      from progression of cervical lesions.

PMID- 9563487
TI  - Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of
      a common lineage.
AB  - Endometriosis is a common gynecological disease in which tissue similar to the
      endometrium proliferates at sites outside the uterine cavity. Malignant
      transformation of endometriosis to endometrioid and clear cell ovarian carcinomas
      has been documented in histological studies, but no molecular genetic evidence
      exists to support that endometriosis is the clonal precursor of such
      malignancies. We examined 14 cases of endometriosis synchronous with ovarian
      cancer for loss of heterozygosity on 12 chromosome arms, X chromosome
      inactivation, and TP53 mutation to determine whether they shared genetic
      alterations. In all four of the cases where the carcinoma had arisen within
      endometriosis and in five of the seven cases where the carcinoma was adjacent to
      the endometriosis, common genetic lesions were detected, consistent with a common
      lineage. A TP53 mutation was also detected in one case of endometriosis adjacent
      to carcinoma. These findings support the numerous histological observations that
      endometrioid and clear cell ovarian carcinomas may arise through malignant
      transformation of endometriotic lesions.

PMID- 9563488
TI  - Microsatellite instability in colorectal cancer: different mutator phenotypes and
      the principal involvement of hMLH1.
AB  - Recent studies have demonstrated the presence of microsatellite instability (MSI)
      in tumors from patients with hereditary nonpolyposis colorectal cancer and in a
      large number of sporadic tumors. To further characterize the type of alterations
      at these loci and their frequency of involvement in colon cancer, we studied DNA
      extracted from paraffin-embedded tissue from 508 patients using 11
      microsatellites localized to chromosomes 5, 8, 15, 17, and 18. Overall, MSI at
      each locus varied in character and frequency and was observed with at least one
      marker in 191 cases (37.6%). Based on the number of markers displaying
      instability per tumor, three groups of patients were defined: those with <30% of
      the markers showing instability (MSI-L,, n = 109, 21.5%); those with > or = 30%
      (MSI-H, n = 82, 16.1%); and those showing no instability (MSS, n = 317, 62.4%).
      These groups were tested for correlations with a number of clinical and
      pathological parameters, including age, sex, stage, ploidy status, and site of
      tumor. Comparing across the three groups and verified by pair-wise comparisons,
      the MSI-H group was associated with tumor site (proximal colon, P = 0.001), sex
      (females, P = 0.005), stage (Dukes' B, P = 0.01), and ploidy status (diploid, P =
      0.03). No significant differences were noted between the MSI-L and MSS group for
      any of the parameters tested. An additional 188 consecutive surgical colorectal
      cancer cases were examined for the presence of MSI and for the
      immunohistochemical expression of hMLH1 and hMSH2 proteins. Of this group, 129
      (68.6%) were classified as MSS, 17 (9.0%) as MSI-L, and 42 (22.3%) as MSI-H. None
      of the MSS and none of the MSI-L tumors had altered expression of either hMLH1 or
      hMSH2. However, the majority of MSI-H (40 of 42, 95%) cases demonstrated absence
      of staining for these proteins. The most frequently altered protein was hMLH1,
      occurring in 95% of the tumors with altered expression. Cumulatively, these data
      suggest that the tumor phenotype MSI-H is distinct from tumor phenotypes MSI-L
      and MSS, with no apparent differences between MSI-L and MSS. Furthermore, altered
      hMLH1 protein expression appears to be responsible for the mutator phenotype in
      the vast majority of MSI-H tumors.

PMID- 9563489
TI  - Two North American families with hereditary papillary renal carcinoma and
      identical novel mutations in the MET proto-oncogene.
AB  - Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited
      disorder characterized by a predisposition to develop multiple bilateral
      papillary renal carcinomas. Individuals affected with HPRC have been shown to
      have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene.
      We identified a novel mutation in exon 16 of the MET gene in two large North
      American HPRC families. The H1112R MET mutation segregated with the disease, was
      not present in 320 normal chromosomes, and caused malignant transformation of NIH
      3T3 cells. By examining individuals with the H1112R mutation, we determined the
      age-dependent penetrance of this mutation and identified additional nonrenal
      malignancies that occurred in mutation carriers. Affected members of the two
      families shared the same haplotype within and immediately distal to the MET gene,
      suggesting a founder effect. The identification of the H1112R mutation will
      facilitate predictive testing in HPRC and guide future studies of the MET gene in
      human neoplasia.

PMID- 9563490
TI  - Antioxidant action via p53-mediated apoptosis.
AB  - The biological effects of antioxidants are often considered in terms of their
      effects on oxygen or lipid radicals. However, antioxidants can also exert their
      effects through altering the cellular redox potential. Herein, we report that
      sulfur-containing antioxidants such as N-acetylcysteine and dimercaptopropanol
      induced apoptosis in several transformed cell lines and transformed primary
      cultures but not in normal cells. In contrast, chain-breaking antioxidants such
      as vitamin E lacked this activity. An increased glutathione level was not
      required for apoptosis; however, all apoptosis-inducing antioxidants elevated the
      total cellular thiol levels. Antioxidant-induced apoptosis required the p53 tumor
      suppressor gene. N-Acetylcysteine elevated p53 expression posttranscriptionally
      by increasing the rate of p53 mRNA translation rather than by altering the
      protein stability. The p53 induction occurred in normal cells. These observations
      indicate a redox sensor for p53 induction in vivo, with additional transformation
      specific information being required for apoptosis. Manipulating p53-dependent
      apoptosis with nontoxic antioxidants may have a direct clinical application.

PMID- 9563491
TI  - Loss or altered subcellular localization of p27 in Barrett's associated
      adenocarcinoma.
AB  - The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell
      division cycle. It is expressed at the highest levels during the quiescent (G0)
      and prereplicative (G1) phases, and its degradation is required for entry into
      the S phase. Because lack of p27 is associated with aggressive behavior in a
      variety of tumors of epithelial and lymphoid origin, we used immunohistochemistry
      and in situ hybridization to evaluate the expression of p27 in metaplastic and
      dysplastic Barrett's epithelium and to assess its prognostic significance in
      Barrett's associated adenocarcinoma (BAA) of the esophagus. In metaplastic
      Barrett's epithelium, p27 protein and mRNA were restricted to the superficial
      third of glands in all cases and extended to the lower third in 4 cases. In
      contrast, expression of p27 message and protein was both increased and full
      thickness, in the 23 cases with high-grade dysplasia adjacent to BAA and in
      carcinoma in situ. Although all invasive carcinomas had elevated levels of p27
      mRNA, 45 (83%) of 54 invasive carcinomas had low p27 protein levels (<50%
      positive tumor cells). Low p27 protein correlated with higher histological grade
      (P < 0.0001), depth of invasion (P = 0.0120), presence of lymph node metastasis
      (P = 0.05), and survival (P = 0.0197). In addition to the nuclear staining,
      cytoplasmic staining of p27 was noted in 11 of 23 (48%) of cases of dysplasia and
      in 14 of 54 (26%) adenocarcinomas and confirmed, in a subset of cases, by
      subcellular fractionation of protein lysates obtained from fresh tumor tissues.
      Cytoplasmic localization of p27 was also associated with decreased survival (P =
      0.0239). Loss of p27 conferred poor prognosis independently of proliferative
      index, as assessed by Ki-67 (MIB-1) immunostaining, which was not significantly
      different in survivors versus nonsurvivors. These results show that: (a)
      distribution of p27 message and protein parallel one another in metaplastic and
      dysplastic Barrett's epithelium, suggesting transcriptional regulation of the
      gene in the nonneoplastic setting; (b) p27 is inactivated in the majority of BAA
      as a result of either post-transcriptional modification or altered subcellular
      localization; and (c) loss of the cell cycle inhibitor p27 is associated with
      parameters of aggressive behavior and unfavorable outcome in BAA.

PMID- 9563492
TI  - Molecular cytogenetic analysis in splenic lymphoma with villous lymphocytes:
      frequent allelic imbalance of the RB1 gene but not the D13S25 locus on chromosome
      13q14.
AB  - Structural abnormalities of chromosome 13q are one of the most frequent genetic
      aberrations in human tumors. 13q rearrangements are, however, infrequent in
      splenic lymphoma with villous lymphocytes (SLVL) by karyotype analysis. We have
      investigated the incidence of 13q14 deletions in a series of 74 SLVL cases by
      interphase fluorescence in situ hybridization using unique sequence probes for
      the RB1 and the D13S25 loci, which are frequently deleted in chronic lymphocytic
      leukemia. Chromosome 12 was also evaluated by fluorescence in situ hybridization
      using a pericentromeric DNA probe. 13q14 deletion was detected in 37 of 74 (50%)
      tumors. Thirty-five cases (47%) exhibited monoallelic loss of RB1, and 9 (12%)
      showed hemizygous D13S25 deletion. Seven cases displayed coexistence of RB1 and
      D13S25 deletion. Trisomy 12 was detected in 2 of 74 (3%) tumors. G-banding
      analysis in 40 tumors showed no interstitial deletion of 13q14 in any case. In
      contrast with the molecular findings observed in chronic lymphocytic leukemia,
      our results indicate that trisomy 12 is an uncommon chromosomal aberration in
      SLVLs, and microdeletion of 13q14 at the RB1 locus but not D13S25 is a frequent
      and specific genetic event in this disease, suggesting that allelic loss of the
      RB1 gene may play a role in the pathogenesis of SLVL.

PMID- 9563493
TI  - Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to
      Fas-mediated apoptosis.
AB  - The Fas system, comprising the Fas receptor (Fas, CD95, APO-1) and its ligand,
      Fas ligand (FasL), is a central mediator of programmed cell death in various
      physiological and pathological processes. Recent evidence indicated that tumor
      cells can exploit this system to their benefit in the dialogue with the host
      immune system. We have shown that all human pancreatic adenocarcinoma cell lines
      tested by fluorescence-activated cell sorting analysis (6 of 6) and
      immunocytochemistry (12 of 12) were positive for Fas expression, as were normal
      and malignant duct cells in pancreatic tissue sections. However, despite Fas
      expression, pancreatic tumor cells have become largely resistant toward
      recombinant FasL- or anti-APO-1 agonistic antibody-induced apoptosis. This
      resistance correlated with high levels in pancreatic tumor cells of mRNA for FAP
      1, a Fas-associated phosphatase that can block the apoptotic function of Fas.
      Using a variety of methodological approaches, we also present evidence for the
      production of FasL by pancreatic tumor cells because 6 of 6 pancreatic tumor cell
      lines were found to contain FasL mRNA as well as the Mr 40,000 and Mr 26,000
      forms of the FasL protein. Likewise, pancreatic tissue revealed FasL-specific
      immunostaining in pancreatic tumor cells but not in the surrounding stroma. In
      coculture experiments, pancreatic tumor cells displayed a cytotoxic effect toward
      the Fas-sensitive Jurkat T-cell line, which could be inhibited by a FasL-specific
      neutralizing antibody. Together, these results support the recently proposed
      "counterattack model" for local deletion of tumor-reactive T-cells by tumor cell
      derived FasL.

PMID- 9563494
TI  - Size-dependent increase in prostanoid levels in adenomas of patients with
      familial adenomatous polyposis.
AB  - Recent studies indicate that nonsteroidal anti-inflammatory drugs have a
      chemopreventive effect against colorectal neoplasia. Nonsteroidal anti
      inflammatory drugs inhibit cyclooxygenases, principal enzymes that mediate the
      formation of prostanoids. To determine whether prostanoids are involved in the
      pathogenesis of colorectal adenomas, we compared the levels of five major stable
      metabolic products of the cyclooxygenase pathway in the normal-appearing mucosa
      and in adenomas of patients with familial adenomatosis polyposis. Of 12 patients
      tested, 6 had elevated levels of at least one prostanoid in the adenomas. More
      importantly, the relative levels of three prostanoids [prostaglandin (PG)D2,
      PGE2, and 6-keto-PGF1alpha] were elevated in adenomas compared to normal
      appearing mucosa from the same patients, and the resulting ratios were correlated
      with the size of the adenoma. These results suggest a role for prostanoids in
      progression of colorectal polyposis in familial adenomatosis polyposis patients.

PMID- 9563495
TI  - Inhibiting Ras prenylation increases the radiosensitivity of human tumor cell
      lines with activating mutations of ras oncogenes.
AB  - The influence of activated ras oncogenes on the sensitivity of human tumor cells
      to killing by radiation has been an unresolved question in radiobiology. We have
      examined this question by measuring the radiation sensitivity of human tumor cell
      lines with oncogenic mutations in their H- or K-ras genes after treatment with
      prenyltransferase inhibitors that prevent the posttranslational modification of
      ras required for its activity. Using two measures of clonogenic survival, we have
      demonstrated radiosensitization in cell lines with oncogenic H-ras mutations or
      with oncogenic K-ras mutations when ras processing was inhibited by
      prenyltransferase inhibitor treatment. In contrast, the inhibition of ras
      processing in cell lines expressing wild-type ras had no effect on radiation
      induced cell death. The prenyltransferase inhibitors themselves inhibited
      clonogenic survival in some cases, but this inhibition did not correlate with ras
      mutational status. Although treatment with prenyltransferase inhibitors and
      radiation resulted in a greater reduction of clonogenicity than either treatment
      alone in cells with wild-type ras, treatment with both agents had a synergistic
      effect on cell killing in tumor cells with ras mutations. Our results demonstrate
      that the inhibition of oncogenic ras activity in human tumor cells can reduce the
      radiation survival of these cells, suggesting that oncogenic ras can contribute
      to radiation resistance in human tumors. These results further demonstrate the
      potential of using prenyltransferase inhibitors in combination with radiotherapy
      in the treatment of human malignancies.

PMID- 9563496
TI  - cdc25 cell cycle-activating phosphatases and c-myc expression in human non
      Hodgkin's lymphomas.
AB  - cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the
      cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B
      have been shown to have oncogenic potential, and they have been identified as
      transcriptional targets of c-myc. To determine the role of cdc25 genes in the
      pathogenesis of human lymphomas and their possible correlation with c-myc
      deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c
      myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid
      tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues
      were negative or negligible. cdc25B overexpression was detected in 35 tumors
      (56%). This overexpression was more frequently found in aggressive (81%) than in
      indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly
      associated with a higher proliferative activity of the tumors. No cdc25B gene
      amplification or rearrangements were detected by Southern blot analysis. A
      biallelic EcoRI polymorphism of cdc25B gene was identified with a similar
      distribution in patients with lymphoma and in a normal population. cdc25A was
      overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels
      were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it
      correlated significantly with the presence of cdc25B up-regulation. Twenty-six of
      35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc
      overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low
      cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a
      significant linear correlation was found between the cdc25B and c-myc mRNA levels
      (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non
      Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and
      it may cooperate with c-myc oncogene in the development of these tumors.

PMID- 9563497
TI  - Rewiring a receptor: negative output from positive input.
AB  - A point mutation or covalent modification in bacterial chemotaxis receptors
      causes bacteria to be repelled by attractants, and attracted to repellents. The
      variety of conditions causing inverse responses suggest that the signal
      transduction mechanism in receptors can be readily rewired to elicit inverse
      responses. A model is presented in which the orientation of a critical residue
      with respect to an active site determines whether the receptor produces normal or
      inverted signals. The model is consistent with observed responses and can be
      generalized to include receptors in other signal transduction systems.

PMID- 9563498
TI  - Enzymes as chaperones and chaperones as enzymes.
AB  - Chaperones and foldases are two groups of accessory proteins which assist
      maturation of nascent peptides into functional proteins in cells. Protein
      disulfide isomerase, a foldase, and ATP-dependent proteases, responsible for
      degradation of misfolded proteins in cells, both have intrinsic chaperone
      activities. Trigger factor and DnaJ, well known Escherichia coli chaperones, show
      peptidyl prolyl isomerase and protein disulfide isomerase activities
      respectively. It is suggested that the combination of chaperone and enzyme
      activities in one molecule is the result of evolution to increase molecular
      efficiency.

PMID- 9563499
TI  - Equilibrium unfolding of a small bacterial cytochrome, cytochrome c551 from
      Pseudomonas aeruginosa.
AB  - The unfolding of the small cytochrome c551 from the bacterium Pseudomonas
      aeruginosa has been characterized at equilibrium by circular dichroism (CD) and
      fluorescence spectroscopy. The process can be described by a two state mechanism
      and the thermodynamic stability of cytochrome c551 is found to be smaller than
      that of the larger horse cytochrome c (deltaGw = -8.2 vs. -9.7 kcal/mol); we
      propose that this finding is related to the absence of an 'omega' loop in the
      bacterial cytochrome. Cytochrome c551 loses most of its secondary structure at pH
      1.5. The acid transition (pKA approximately 2) is highly cooperative (n > or =2);
      analysis of optical titrations and contact map suggests that (at least) His-16
      (proximal Fe3+ ligand) and Glu-70 are both involved in the acid transition. The
      role of selected hydrophobic, electrostatic and conformational contributions to
      the overall stability has been investigated by protein engineering. The
      equilibrium characterization of wild-type and mutant cytochrome c551 supports the
      view that this small cytochrome is an interesting protein to analyze the
      thermodynamics and the kinetics of folding in comparison with the widely studied
      horse cytochrome c.

PMID- 9563500
TI  - Homology between a human apoptosis specific protein and the product of APG5, a
      gene involved in autophagy in yeast.
AB  - Apoptosis specific proteins (ASP) are expressed in the cytoplasm of cultured
      mammalian cells of various lineages following induction of apoptosis. The cDNA
      encoding ASP has been cloned from a human expression library and has significant
      homology to the Saccharomyces cerevisiae APG5 gene which is essential for yeast
      autophagy. The ASP gene, known as hAPG5, can be transcribed to give mRNAs of 3.3
      kbp, 2.5 kbp and 1.8 kbp which are present at comparable levels in viable and
      apoptotic cells, demonstrating that protein expression must be regulated at the
      translational level. These data indicate a possible relationship between
      apoptosis and autophagy and suggest evolutionary conservation in mammalian
      apoptosis of a degradative process present in yeast.

PMID- 9563501
TI  - Bicarbonate binding to the water-oxidizing complex in the photosystem II. A
      Fourier transform infrared spectroscopy study.
AB  - The light-induced Fourier transform infrared difference (FT-IR) spectrum
      originating from the donor side of O2-evolving photosystem (PS) II was obtained
      in non-depleted and CO2-depleted PSII membrane preparations. The observed
      spectrum free of contributions from the acceptor side signals was achieved by
      employing 2 mM/18 mM ferri-/ferrocyanide as a redox couple. This spectrum showed
      main positive bands at 1589 and 1365 cm(-1) and negative bands at 1560, 1541,
      1522 and 1507 cm(-1). CO-depleted PSII preparations showed a quite different
      spectrum. The main positive and negative bands disappeared after depletion of
      bicarbonate. The addition of bicarbonate partially restored those bands again.
      Comparison between difference FT-IR spectra of untreated and bicarbonate-depleted
      PSII membranes indicated that the positive bands at 1589 and 1365 cm(-1) can be
      assigned to COO- stretching modes from bicarbonate. The higher frequency
      corresponds to u[as] (COO-) and the lower frequency to u[s] (COO-). 13C-Labeling
      FT-IR measurements confirmed these findings and also suggested that the negative
      band at 1560 cm(-1) can be ascribed to u[as] (COO-). The data are discussed in
      the framework of the suggestion that bicarbonate can be a ligand to the Mn
      containing water-oxidizing complex of PSII.

PMID- 9563502
TI  - Polypyrimidine tract-binding protein interacts with HnRNP L.
AB  - Polypyrimidine tract-binding protein (PTB) is involved in pre-mRNA splicing and
      internal ribosomal entry site (IRES)-dependent translation. In order to identify
      cellular protein(s) interacting with PTB, we performed a yeast two-hybrid
      screening. Heterogeneous nuclear ribonucleoprotein L (hnRNP L) was identified as
      a PTB-binding protein. The interaction between PTB and hnRNP L was confirmed in
      an in vitro binding assay. Both PTB and hnRNP L were found to localize in the
      nucleoplasm, excepting the nucleoli, in HeLa cells by the green fluorescent
      protein (GFP)-fused protein detection method. The N-terminal half of PTB (aa 1
      329) and most of hnRNP L (aa 141-558) is required for the interaction between PTB
      and hnRNP L.

PMID- 9563503
TI  - The role of the C-terminus for catalysis of the large thioredoxin reductase from
      Plasmodium falciparum.
AB  - The thioredoxin system is one of the major thiol reducing systems of the cell.
      Recent studies have revealed that Plasmodium falciparum and human thioredoxin
      reductase represent a novel class of enzymes, which are substantially different
      from the isofunctional prokaryotic Escherichia coli enzyme. We identified the
      cysteines Cys88 and Cys93 as the redox active disulfide and His509 as the active
      site base [Gilberger, T.-W., Walter, R.D. and Muller, S., J. Biol. Chem. 272
      (1997) 29584-29589]. In addition to the active site thiols Cys88 and Cys93 the P.
      falciparum enzyme has another pair of cysteines at the C-terminus: Cys535 and
      Cys540. To assess the possible role of these peripheral cysteines in the
      catalytic process the single mutants PfTrxRC535A and PfTrxRC540A, the double
      mutant P/TrxRC535AC540A and the deletion mutant PfTrxRdelta9 (C-terminal deletion
      of the last nine amino acids) were constructed. All mutants are defective in
      their thioredoxin reduction activity, although they still show reactivity with
      5,5'-dithiobis (2-nitrobenzoate). These data imply that the C-terminal cysteines
      are crucially involved in substrate coordination and/or electron transfer during
      reduction of the peptide substrate.

PMID- 9563504
TI  - Is absence of pyruvate dehydrogenase complex in mitochondria a possible
      explanation of significant aerobic glycolysis by normal human leukocytes?
AB  - The oxygen consumption of leukocyte mitochondria of both healthy donors and
      leukemic patients was tested by using different respiratory substrates. The
      results indicate that pyruvate could not be utilized by mitochondria of normal
      leukocytes, whereas mitochondria of leukemic leukocytes could use pyruvate as a
      good respiratory substrate. A search for the possible presence of pyruvate
      dehydrogenase complex (PDC) in leukocytes indicates that this enzyme is
      apparently absent in mitochondria of normal leukocytes but is quite active in
      mitochondria of leukemic leukocytes. The absence of PDC in normal leukocyte
      mitochondria can explain the phenomenon of significant aerobic glycolysis that
      has been observed in normal leukocytes.

PMID- 9563505
TI  - Structural plasticity of the feline leukaemia virus fusion peptide: a circular
      dichroism study.
AB  - The secondary structure of the feline leukaemia virus (FeLV) fusion peptide was
      investigated using circular dichroism (CD). Our results show that this peptide
      can readily flip between random, alpha-helical and beta-sheet conformations,
      depending upon its environment. The CD spectrum changes from one characteristic
      of random coil to predominantly beta-sheet type, and finally to that showing the
      characteristics of alpha-helical structure on moving from an aqueous solvent,
      through several increasingly hydrophobic systems, to a highly hydrophobic
      solvent. Electron microscopy confirmed the presence of beta structure. We propose
      that the structural plasticity demonstrated here is crucial to the ability of the
      fusion peptide to perturb lipid bilayers, and thus promote membrane fusion.

PMID- 9563506
TI  - The endogenous cannabinoid anandamide is a lipid messenger activating cell growth
      via a cannabinoid receptor-independent pathway in hematopoietic cell lines.
AB  - The effect of anandamide, an endogenous ligand for central (CB1) and peripheral
      (CB2) cannabinoid receptors, was investigated on the growth of the murine IL-6
      dependent lymphoid cell line B9 and the murine IL-3-dependent myeloblastic cell
      line FDC-P1. In conditions of low serum level, anandamide potentiated the growth
      of both cytokine-dependent cell lines. Comparison with other fatty acid
      cannabinoid ligands such as (R)-methanandamide, a ligand with improved
      selectivity for the CB1 receptor, or palmitylethanolamide, an endogenous ligand
      for the CB2 receptor, showed a very similar effect, suggesting that cell growth
      enhancement by anandamide or its analogs could be mediated through either
      receptor subtype. However, several lines of evidence indicated that this growth
      promoting effect was cannabinoid receptor-independent. First, the potent
      synthetic cannabinoid agonist CP 55940, which displays high affinity for both
      receptors, was inactive in this model. Second, SR 141716A and SR 144528, which
      are potent and specific antagonists of CB1 and CB2 receptors respectively, were
      unable, alone or in combination, to block the anandamide-induced effect. Third,
      inactivation of both receptors by pretreatment of cells with pertussis toxin did
      not affect the potentiation of cell growth by anandamide. These data demonstrated
      that neither CB1 nor CB2 receptors were involved in the anandamide-induced
      effect. Moreover, using CB2-transfected Chinese hamster ovary cells, we
      demonstrated that after complete blockade of the receptors by the specific
      antagonist SR 144528, anandamide was still able to strongly stimulate a mitogen
      activated protein (MAP) kinase activity, clearly indicating that the endogenous
      cannabinoid can transduce a mitogenic signal in the absence of available
      receptors. Finally, arachidonic acid, a structurally related compound and an
      important lipid messenger without known affinity for cannabinoid receptors, was
      shown to trigger MAP kinase activity and cell growth enhancement similar to those
      observed with anandamide. These findings provide clear evidence for a functional
      role of anandamide in activating a signal transduction pathway leading to cell
      activation and proliferation via a non-cannabinoid receptor-mediated process.

PMID- 9563507
TI  - A novel basement membrane-induced gene identified in the human endometrial
      adenocarcinoma cell line HEC1B.
AB  - Cultured HEC1B human endometrial adenocarcinoma cells respond to reconstituted
      basement membrane (Matrigel) by morphological and functional differentiation in
      vitro. Our goal is to identify genes involved in this differentiation process. By
      means of rt-PCR, we were able to isolate the novel 2.4 kb Matrigel-induced
      transcript icb-1 containing an open reading frame predicting a 31.7 kDa protein.
      The time-dependent induction of icb-1 gene expression by basement membrane was
      confirmed by Northern blot experiments. In a data bank search, several EST
      homologues corresponding to the 3' untranslated region could be found. In
      summary, icb-1 as a new tool enables us to study molecular mechanisms of cell
      matrix interactions contributing to carcinogenesis.

PMID- 9563508
TI  - hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB
      activity.
AB  - hUBC9, an E2 ubiquitin conjugating enzyme, was identified by yeast two-hybrid
      screening and coprecipitation studies to interact with MEKK1 and the type I TNF
      alpha receptor, respectively. Because both of these proteins regulate NFkappaB
      activity, the role of hUBC9 in modulating NFkappaB activity was investigated.
      Overexpression of hUBC9 in HeLa cells stimulated the activity of NFkappaB as
      determined by NFkappaB reporter and IL-6 secretion assays. hUBC9 also synergized
      with MEKK1 to activate NFkappaB reporter activity. Thus, hUBC9 modulates NFkappaB
      activity which, at least in part, can be attributed to its interaction with MEKK1
      and the type I TNF-alpha receptor.

PMID- 9563509
TI  - Direct gene transfer into rat liver cells by in vivo electroporation.
AB  - In vivo electro-transfection efficiency and manner of transferred gene expression
      were investigated by fluorescence microscopic image analysis. Green fluorescent
      protein (GFP) gene was used as the genetic marker. Electroporation was carried
      out on the liver of live rats by use of disk electrodes mounted in the tips of
      tweezers, which were directly pressed onto the surface of a liver lobe in situ.
      Electroporation with eight electric pulses of 50 ms in duration at 50 V gave a
      good efficiency of transfection as judged by the induced GFP expression. Bright
      fluorescence of GFP appeared as dots, which were scattered around the area
      damaged by electroporation. The transfection efficiency increased as the amount
      of injected DNA was increased. The results indicate that the amount of induced
      gene expression can be controlled. Estimation of the efficiency of electro-gene
      transfer using the fluorescence of GFP and digital analysis of microscopic images
      was useful to determine the optimum conditions for local gene therapy in tissues
      and organs.

PMID- 9563510
TI  - Intercellular communication between vascular smooth muscle and endothelial cells
      mediated by heparin-binding epidermal growth factor-like growth factor and
      vascular endothelial growth factor.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent
      mitogen and migration factor for vascular smooth muscle cells (SMC), promoted
      neovascularization in vivo in the rabbit cornea. MRI demonstrated quantitatively
      the angiogenic effect of HB-EGF when introduced subcutaneously into nude mice. HB
      EGF is not directly mitogenic to endothelial cells but it induced the migration
      of bovine endothelial cells and release of endothelial cell mitogenic activity
      from bovine vascular SMC. This mitogenic activity was specifically blocked by
      neutralizing anti-vascular endothelial growth factor (VEGF) antibodies. In
      contrast, EGF or transforming growth factor-alpha (TGF-alpha) had almost no
      effect on release of endothelial mitogenicity from SMC. In addition, RT-PCR
      analysis demonstrated that VEGF165 mRNA levels were increased in vascular SMC 4
      10-fold by 0.35-2 nM of HB-EGF, respectively. Our data suggest that HB-EGF, as a
      mediator of intercellular communication, may play a new important role in
      supporting wound healing, tumor progression and atherosclerosis by stimulating
      angiogenesis.

PMID- 9563511
TI  - Elucidation of the cause for reduced activity of abnormal human plasmin
      containing an Ala55-Thr mutation: importance of highly conserved Ala55 in serine
      proteases.
AB  - In serine proteases, Ala55 is highly conserved and located just behind the
      catalytic triad. That the activity of human plasmin is reduced by the A55T
      substitution indicates the importance of Ala55 in catalysis. In the present
      study, the 3-D model of A55T human plasmin shows that an unusual hydrogen bond
      between Thr55 Ogamma1 and His57 Nepsilon2 alters His57 into an inactive
      conformation in which His57 cannot accept a proton from Ser195 as a catalytic
      base. Our results demonstrate that Ala55 contributes heavily to the active
      conformation of His57 and ensures the proton transfer from Ser195 to His57.

PMID- 9563512
TI  - Regulation of the glial glutamate transporter GLT-1 by glutamate and delta-opioid
      receptor stimulation.
AB  - The excitatory effect of presynaptically released glutamate is tightly regulated
      and terminated by high affinity sodium-dependent glutamate transporters. The
      regulation of the glial glutamate transporter GLT-1 is potentially important in
      synaptic modulation. Using astroglial cultures prepared from the rat cerebral
      cortex, we found that the delta-opioid receptor agonist [D-pen2,D-pen5]
      enkephalin decreases and glutamate increases the expression of the GLT-1
      transporter mRNA. Corresponding changes in the uptake kinetics were found after
      incubation for 48 h with the respective agonists when glial glutamate uptake was
      measured in primary astroglial cultures. The data suggest that long-term receptor
      activation induces alterations in glial glutamate uptake properties.

PMID- 9563513
TI  - Moderate discrimination of REP-1 between Rab7 x GDP and Rab7 x GTP arises from a
      difference of an order of magnitude in dissociation rates.
AB  - The kinetics of the interaction of Rab7 with REP-1 have been investigated using
      the fluorescence of GDP and GTP analogs at the active site of Rab7. The results
      show that REP-1 has higher affinity for the GDP bound form of Rab7 (Kd=1 nM) than
      for the GTP bound form (Kd=20 nM). Both affinities should still be sufficient for
      the formation of stable complexes in the cell. The association reaction proceeds
      in two steps for the GDP bound form. The initial step is fast (k+1 = ca. 10[7] M[
      1] s[-1]) and concentration dependent while the second represents a slow
      equilibration (k+2 + k-2 = 3.5 s[-1]) which has little effect on the overall
      equilibrium. The difference in affinity of the two nucleotide bound forms arises
      from a difference in dissociation rates (0.012 s[-1] for Rab7 x GDP and 0.2 s[-1]
      for Rab7 x GTP).

PMID- 9563515
TI  - Evidence against protein kinase B as a mediator of contraction-induced glucose
      transport and GLUT4 translocation in rat skeletal muscle.
AB  - Both insulin and muscle contraction stimulate glucose transport activity.
      However, contraction stimulation does not involve the insulin signalling
      intermediate phosphatidylinositol 3-kinase (PI 3-kinase). Protein kinase B (PKB)
      has recently been identified as a direct downstream target of PI 3-kinase in the
      insulin signalling pathway. We have examined here whether the two stimuli share
      PKB as a convergent step in separate signalling pathways. Insulin stimulates both
      glucose transport, GLUT4 cell-surface content and PKB activity (by 4-6-fold above
      basal) in a wortmannin-sensitive manner in in vitro incubated rat soleus muscles.
      By contrast, muscle contraction, which stimulates glucose transport and the cell
      surface content of GLUT4 by 3-fold above basal levels, had no effect on PKB
      activity. These data demonstrate that PKB is not a mediator of contraction
      induced glucose transport and GLUT4 translocation.

PMID- 9563514
TI  - Human retinoblastoma protein (Rb) is phosphorylated by cdc2 kinase and MAP kinase
      in Xenopus maturing oocytes.
AB  - Xenopus oocyte meiotic maturation combines features of G0/G1 and G2/M transitions
      of the cell cycle. To study the in ovo Rb kinase activity, we have microinjected
      human Rb into oocytes. Microinjected human Rb localizes into the nucleus, is
      hypophosphorylated in prophase oocytes, becomes hyperphosphorylated during
      meiotic maturation and is dephosphorylated as the cell reenters interphase.
      Inactivation or overexpression of the cyclin D-cdk4/6 complex in an oocyte
      extract does not affect the Rb kinase activity. This kinase activity could be
      attributed to both cdc2-cyclin B and MAP kinase, opening new perspectives of
      investigation in somatic cells.

PMID- 9563516
TI  - Hexokinase PII has a double cytosolic-nuclear localisation in Saccharomyces
      cerevisiae.
AB  - We describe here that the HXK2 gene product, isoenzyme PII of hexokinase, is
      located in both the nucleus and the cytoplasm of Saccharomyces cerevisiae cells.
      This conclusion is supported by assays of hexokinase-specific activity in
      isolated nuclei from wild-type and hxk1lhxk2 double mutant strains, by immunoblot
      experiments using anti-Hxk2 antibodies and by observation of the fluorescence
      distribution of a Hxk2-GFP fusion protein in cells transformed with the HXK2::gfp
      gene.

PMID- 9563517
TI  - Orientation of antigen binding sites in dimeric and trimeric single chain Fv
      antibody fragments.
AB  - Electron microscopy of dimeric and trimeric single chain antibody Fv fragments
      (scFvs) complexed with anti-idiotype Fab fragments was used to reveal the
      orientation of antigen binding sites. This is the first structural analysis that
      discloses the multivalent binding orientation of scFv trimers (triabodies). Three
      different scFv molecules were used for the imaging analysis; NC10 scFv-5 and scFv
      0, with five- and zero-residue linkers respectively between the VH and VL
      domains, were complexed with 3-2G12 anti-idiotype Fab fragments and 11-1G10 scFv
      0 was complexed with NC41 anti-idiotype Fab fragments. The scFv-5 molecules
      formed bivalent dimers (diabodies) and the zero-linker scFv-0 molecules formed
      trivalent trimers (triabodies). The images of the NC10 diabody-Fab complex appear
      as boomerangs, not as a linear molecule, with a variable angle between the two
      Fab arms and the triabody-Fab complexes appear as tripods.

PMID- 9563518
TI  - In vitro interaction of the carboxy-terminal domain of lamin A with actin.
AB  - The nuclear lamina formed by lamins is localized between the inner nuclear
      membrane and chromatin. Lamins are thought to be implicated in the higher order
      chromatin structure. Interactions of lamins with chromatin have been described
      but the molecular components directly involved in these interactions remain to be
      identified. Using a GST-C-terminal domain of lamin A fusion protein to probe
      cellular extracts for interacting proteins, we have found that this domain of
      lamin A binds to nuclear actin. This result suggests that an actin-based
      molecular motor linked to the lamina could be involved in the movement of
      chromatin domains.

PMID- 9563519
TI  - A novel lipopolysaccharide inducible C-C chemokine receptor related gene in
      murine macrophages.
AB  - To identify genes induced in activated macrophages, we screened a cDNA library
      prepared from the lipopolysaccharide (LPS)-treated cell line, RAW264, using the
      suppression subtractive hybridization technique. One of the clones isolated was
      dramatically induced by LPS in macrophages. The predicted protein sequence of
      this gene contains the domain unique to seven transmembrane receptors, and shows
      similarity with mouse C-C chemokine receptor 5 (CCR5). Therefore, we designated
      it LPS inducible C-C chemokine receptor related gene (L-CCR). Northern blot
      analysis revealed that L-CCR was specifically expressed in differentiated
      macrophages after LPS stimulation. These results show that L-CCR is a novel C-C
      chemokine receptor related gene induced by LPS in macrophages and may play an
      important role in inflammatory responses.

PMID- 9563520
TI  - The dipyridyls paraquat and diquat attenuate the interaction of G-actin with
      thymosin beta4.
AB  - Beta-thymosins sequester G-actin and preserve a pool of monomers of actin which
      constitute an important prerequisite for cellular function of the microfilament
      system. To study the influence of paraquat binding to G-actin on the interaction
      of G-actin with thymosin beta4 we determined the apparent dissociation constant
      of the G-actin-thymosin beta4 complex in the absence or presence of paraquat
      using an ultrafiltration assay. Paraquat (1,1'-dimethyl-4,4'-dipyridylium
      dichloride) attenuates this interaction in a concentration- and time-dependent
      manner. When exposed to 10 mM paraquat, the apparent dissociation constant
      increased 10-85-fold within 15 min to 24 h. After incubation for 24 h even a
      paraquat concentration as low as 100 microM increased the dissociation constant
      of the G-actin-thymosin beta4 complex from 0.66 microM to 0.82 microM (P < 0.05).
      Diquat (1,1'-ethylene-2,2'-dipyridylium dibromide) similarly weakens the
      interaction of G-actin and beta-thymosins. In none of the experiments was
      oxidation of the methionine residue or any other modification of thymosin beta4
      detected. Therefore we conclude that the dipyridyls paraquat and diquat directly
      interact with G-actin and thereby impede the interaction between G-actin and
      thymosin beta4.

PMID- 9563521
TI  - p53-independent DNA repair and cell cycle arrest in embryonic stem cells.
AB  - The role of p53 in DNA repair and cell cycle checkpoint after ultraviolet
      irradiation was investigated in an embryonic stem cell line homozygous for a
      targeted deletion of p53. Results indicate that loss of p53 does not alter the
      capacity of ES cells to respond to DNA damage. Wild-type and p53-deficient cells
      showed similar cessation of DNA synthesis after UV damage and similar ultimate
      capacity to repair a transiently transfected reporter plasmid. Interestingly, in
      the absence of DNA damaging treatment, the transit of p53-deficient cells through
      S phase was slower than wild-type cells. We suggest that this may result from the
      absence of a p53-dependent response to endogenous DNA damage: without p53 sensing
      endogenous damage leading to immediate repair, such damage may persist and thus
      delay DNA synthesis.

PMID- 9563522
TI  - Projection map of the reaction center-light harvesting 1 complex from
      Rhodopseudomonas viridis at 10 A resolution.
AB  - The photosynthetic reaction center-light harvesting 1 complex from
      Rhodopseudomonas viridis was purified and reconstituted into two-dimensional
      crystals. The single-layered crystalline sheets with lattice parameters a=b=133.3
      A and gamma=120 degrees were investigated by electron cryo-microscopy and the
      projection map at 10 A resolution was calculated. The opening diameter of the
      light-harvesting ring of 72 A is sufficient to allow slight movement of the
      reaction center within the ring. Based on characteristic features observed in the
      projection map, the mechanism of energy transfer from the light-harvesting 1
      complex to the reaction center was discussed.

PMID- 9563523
TI  - Phospholamban domain I/cytochrome b5 transmembrane sequence chimeras do not
      inhibit SERCA2a.
AB  - A series of chimeras between the transmembrane domains of phospholamban (PLN) and
      cytochrome b5 were coexpressed with the Ca2+-ATPase of cardiac sarcoplasmic
      reticulum (SERCA2a). The chimeric molecules were not inhibitory, in line with our
      view that inhibitory PLN/SERCA2a interactions occur in transmembrane sequences,
      while cytoplasmic interactions regulate the inhibitory interactions in a four
      base circuit.

PMID- 9563524
TI  - Repeated, protein-encoding heterochromatic genes cause inactivation of a
      juxtaposed euchromatic gene.
AB  - Euchromatic genes are often silenced by rearrangements that place them within or
      near heterochromatin, a phenomenon known as position effect variegation (PEV).
      However, little is known about molecular structure of cis-acting heterochromatic
      fragments responsible for PEV. Here we report that heterochromatic cluster
      containing Stellate repeats, that encode putative regulatory subunit of protein
      kinase CK2 cause PEV of a reporter white 'mini-gene'. It is the first example of
      an euchromatic gene being silenced because of the proximity to the natural, well
      defined heterochromatic repeat cluster.

PMID- 9563525
TI  - Genetic engineering, production and characterisation of monomeric variants of the
      dimeric Serratia marcescens endonuclease.
AB  - The Serratia nuclease is a non-specific endonuclease which cleaves single- and
      double-stranded RNA and DNA. It is a member of a large family of related
      endonucleases, most of which are dimers of identical subunits, with the notable
      exception of the Anabaena nuclease which is a monomer. In order to find out
      whether the dimer state of the Serratia nuclease is essential for its function we
      have produced variants of this nuclease which based on the crystal structure
      (Miller, M.D. and Krause, K.L. (1996), Protein Science 5, 24-33) were expected to
      be unable to dimerise. We demonstrate here that these variants, H184A, H184N,
      H184T and H184R, are monomers and have the same secondary structure, stability
      towards chemical denaturation and activity as the wild-type enzyme. This allows
      to conclude that the dimeric state is not essential for the catalytic function of
      the Serratia nuclease. In contrast, the S179C variant which is also a monomer
      shows little activity, presumably because this amino acid substitution changes
      the structure of the enzyme.

PMID- 9563526
TI  - NMR analyses of the interactions of human annexin I with ATP, Ca2+, and Mg2+.
AB  - Human annexin I is a member of the annexin family of calcium-dependent
      phospholipid binding proteins. The structure of an N-terminally truncated human
      annexin I (delta-annexin I) and its interactions with Ca2+, Mg2+, and ATP were
      studied at the atomic level using nuclear magnetic resonance (NMR) spectroscopy.
      Since delta-annexin I is a large protein, with a molecular weight of 35 kDa, a
      site-specific (carbonyl-13C, amide-15N) labeling technique was used to determine
      the interaction sites of delta-annexin I with Ca2+, Mg2+, and ATP. The 13C NMR
      study focused on the carbonyl carbon resonances of the histidine residues of
      delta-annexin I. We found that ATP binds to delta-annexin I, and that the ATP
      binding site is located in the 1-domain of annexin I. We also found that
      histidine-52 is involved in that site, and that the binding ratio of ATP to delta
      annexin I is 1:1.

PMID- 9563527
TI  - The presence of dehydroascorbate and dehydroascorbate reductase in plant tissues.

PMID- 9563528
TI  - Dehydroascorbate reduction: the phantom remaining.

PMID- 9563529
TI  - Prospective randomized study of early versus delayed laparoscopic cholecystectomy
      for acute cholecystitis.
AB  - OBJECTIVE: A prospective randomized study was undertaken to compare early with
      delayed laparoscopic cholecystectomy for acute cholecystitis. SUMMARY BACKGROUND
      DATA: Laparoscopic cholecystectomy for acute cholecystitis is associated with
      high complication and conversion rates. It is not known whether there is a role
      for initial conservative treatment followed by interval elective operation.
      METHOD: During a 26-month period, 99 patients with a clinical diagnosis of acute
      cholecystitis were randomly assigned to early laparoscopic cholecystectomy within
      72 hours of admission (early group, n = 49) or delayed interval surgery after
      initial medical treatment (delayed group, n = 50). Thirteen patients (four in the
      early group and nine in the delayed group) were excluded because of refusal of
      operation (n = 6), misdiagnosis (n = 5), contraindication for surgery (n = 1), or
      loss to follow-up (n = 1). RESULTS: Eight of 41 patients in the delayed group
      underwent urgent operation at a median of 63 hours (range, 32 to 140 hours) after
      admission because of spreading peritonitis (n = 3) and persistent fever (n = 5).
      Although the delayed group required less frequent modifications in operative
      technique and a shorter operative time, there was a tendency toward a higher
      conversion rate (23% vs. 11%; p = 0.174) and complication rate (29% vs. 13%; p =
      0.07). For 38 patients with symptoms exceeding 72 hours before admission, the
      conversion rate remained high after delayed surgery (30% vs. 17%; p = 0.454). In
      addition, delayed laparoscopic cholecystectomy prolonged the total hospital stay
      (11 days vs. 6 days; p < 0.001) and recuperation period (19 days vs. 12 days; p <
      0.001). CONCLUSIONS: Initial conservative treatment followed by delayed interval
      surgery cannot reduce the morbidity and conversion rate of laparoscopic
      cholecystectomy for acute cholecystitis. Early operation within 72 hours of
      admission has both medical and socioeconomic benefits and is the preferred
      approach for patients managed by surgeons with adequate experience in
      laparoscopic cholecystectomy.

PMID- 9563530
TI  - Acute cholecystitis revisited: get it while it's hot.

PMID- 9563531
TI  - "Renal dose" dopamine in surgical patients: dogma or science?
AB  - OBJECTIVE: "Renal dose" dopamine is widely used in the perioperative period to
      provide renal protection. A comprehensive review of the literature was performed
      to determine whether dopamine does in fact confer protection on the kidneys of
      surgical patients. SUMMARY BACKGROUND DATA: Studies in healthy animals and human
      volunteers reveal that dopamine causes diuresis and natriuresis, as well as some
      degree of renal vasodilatation. RESULTS: Studies of the perioperative use of
      dopamine fail to demonstrate any benefit of dopamine in preventing renal failure.
      Studies in congestive heart failure, critical illness, and sepsis also fail to
      show any benefit of dopamine other than diuresis. Further, dopamine
      administration is not completely without risk, because of dopamine's
      catecholamine and neuroendocrine functions. CONCLUSIONS: Routine use of
      prophylactic "renal dose" dopamine in surgical patients is not recommended.

PMID- 9563533
TI  - Task performance in endoscopic surgery is influenced by location of the image
      display.
AB  - OBJECTIVE: To investigate the influence of image display location on endoscopic
      task performance in endoscopic surgery. SUMMARY BACKGROUND DATA: The image
      display system is the only visual interface between the surgeon or
      interventionist and the operative field. Several factors influence the correct
      perceptual processing and endoscopic manipulation from images. One of these is
      location of the image display with respect to the surgeon and to the operative
      site. The present study was conducted to investigate whether endoscopic task
      performance improves under two conditions: when the surgeon-to-monitor visual
      axis is aligned with the forearm-instrument motor axis and when the image display
      is close to the operator's manipulation workspace. METHODS: An endoscopic task
      (tying an intracorporeal surgeon's knot) was performed under standardized
      conditions except for varying monitor locations. These altered the direction of
      view--in front of, to the left, and to the right of the operator's head and
      hands. In each of these view directions, the monitor was placed at the surgeon's
      eye level and lower down, at the level of the operator's hands. The outcome
      measures were the execution time, knot quality score and performance quality
      score. RESULTS: Task performance was better with frontal view direction:
      execution time was shorter (p < 0.0001) and the performance score was higher (p <
      0.005) than with side viewing, with no significant difference between right and
      left viewing directions. With frontal view direction, hand-level "gaze-down"
      viewing resulted in a shorter execution time (p < 0.01) and a higher performance
      score (p < 0.01) than eye-level viewing. CONCLUSIONS: Task performance improves
      when the image display is placed in front of the operator, at a level below the
      head and close to the hands.

PMID- 9563532
TI  - Hemodynamic effects of the laparoscopic pneumoperitoneum during sepsis in a
      porcine endotoxic shock model.
AB  - OBJECTIVE: The authors compared the hemodynamic effects of laparoscopic
      intervention with conventional laparotomy in an endotoxic shock model in the pig.
      SUMMARY BACKGROUND DATA: Laparoscopic techniques are being applied more
      frequently to severely ill patients to evaluate potential abdominal sources of
      sepsis. Although hemodynamic effects of laparoscopy are minimal in healthy
      patients, recent studies have shown more significant changes in patients with
      chronic cardiopulmonary disease. It is unclear whether these effects are
      applicable to acutely septic patients. METHODS: Twelve domestic pigs received
      intravenous lipopolysaccharide (LPS) injection and underwent surgical abdominal
      exploration using either laparoscopy or conventional laparotomy. For baseline
      comparison, four pigs underwent exploratory laparoscopy without intravenous LPS
      injection. Hemodynamic measurements and blood gas analyses were obtained using
      Swan-Ganz and arterial catheters. RESULTS: After LPS exposure, animals undergoing
      laparoscopic evaluation were significantly more hypercarbic (p < 0.01) and
      acidotic (p < 0.01) than those undergoing conventional laparotomy. Their mean
      pulmonary arterial pressure and pulmonary vascular resistance were greater as
      well (not significant). The cardiac index (p < 0.05) and stroke volume (p < 0.05)
      were decreased in the laparoscopic group. Their oxygen delivery was decreased and
      oxygen consumption increased, although these were not significantly different
      from those of the laparotomy group. The degree of acidosis was highly correlated
      with the cardiac index (correlation coefficient, r = 0.82). CONCLUSIONS: Animals
      exposed to LPS tolerate laparoscopy but with significant hemodynamic compromise.
      Much of this effect seems to be mediated by a cardiodepressive effect of
      acidosis. This study suggests that laparoscopic intervention, when used in septic
      patients, should be used with caution.

PMID- 9563534
TI  - Effects of glutamine supplements and radiochemotherapy on systemic immune and gut
      barrier function in patients with advanced esophageal cancer.
AB  - OBJECTIVE: The objective of this study was to determine whether oral glutamine
      supplements can protect lymphocyte and gut barrier function in patients with
      advanced esophageal cancer undergoing radiochemotherapy. SUMMARY BACKGROUND DATA:
      Glutamine supplements improved protein metabolism in tumor bearing rats who
      underwent chemotherapy and reduced the toxicity of chemotherapy through an
      enhancement of glutathione production in rats. METHODS: Thirteen patients with
      esophageal cancer were randomly placed in either a control or a glutamine group.
      Glutamine was administered orally (30 g/day) at the start of radiochemotherapy
      and for the subsequent 28 days. All patients underwent mediastinal irradiation
      and chemotherapy consisting of 5-fluorouracil and cisplatin. The lymphocyte count
      was determined, and blast formation was assessed after stimulation with
      phytohemagglutinin and concanavalin A. Gut barrier function was assessed by
      measuring the total amount of phenolsulfonphthalein excreted in the urine after
      the oral administration of phenolsulfonphthalein. RESULTS: Glutamine supplements
      prevented a reduction in the lymphocyte count (control: 567 +/- 96/mm3 vs.
      glutamine: 1007 +/- 151, p < 0.05), and blast formation of lymphocyte
      (phytohemagglutinin, control: 19478 +/- 2121 dpm vs. glutamine: 33860 +/- 1433, p
      < 0.01, concanavalin A, control: 19177 +/- 1897 dpm vs. glutamine: 29473 +/-
      2302, p < 0.01), and amount of phenolsulfonphthalein excretion in the urine was
      greater with control than with glutamine group (control: 15.4 +/- 2.4% vs.
      glutamine: 7.4 +/- 1.2, p < 0.05) 7 days after the initiation of
      radiochemotherapy. CONCLUSIONS: Oral glutamine supplementation protects
      lymphocytes and attenuates gut permeability in patients with esophageal cancer
      during radiochemotherapy.

PMID- 9563535
TI  - Comparison of primary and reoperative surgery in patients with Crohns disease.
AB  - OBJECTIVE: This study was performed to determine the clinical results of patients
      with Crohns disease who require surgical resection. The outcome of patients
      undergoing initial surgery was compared with those having reoperation. METHODS:
      One hundred sixty-four patients undergoing intestinal resection for Crohns
      disease at The Mount Sinai Hospital from 1976 to 1989 were studied prospectively.
      The mean duration of follow-up was 72 months. RESULTS: Ninety patients (55%)
      underwent initial intestinal resection whereas 74 patients (45%) underwent
      reoperation for recurrent disease. Patients undergoing reoperation were older
      (33.4 vs. 38.7 years), had longer durations of disease (8.7 vs. 15.2 years), had
      shorter resections (60 vs. 46 cm), and were more likely to require ileostomy.
      Forty-seven percent of the patients with multiple previous resections required an
      ileostomy. This group also received a mean of 2.3 U blood in the perioperative
      period and showed a trend to increased symptomatic recurrence (49% vs. 71% at 5
      years). CONCLUSIONS: Patients with Crohns disease undergoing first and second
      reoperation have outcomes similar to those in patients undergoing primary
      resection. Patients requiring multiple reoperations are more likely to require
      blood transfusions and permanent ileostomy and to show a greater trend to early
      symptomatic recurrence.

PMID- 9563536
TI  - Use of paravertebral block anesthesia in the surgical management of breast
      cancer: experience in 156 cases.
AB  - OBJECTIVE: To assess safety and efficacy of the regional anesthetic technique
      paravertebral block for operative treatment of breast cancer, and to compare
      postoperative pain, nausea, vomiting, and length of hospital stay in patients
      undergoing breast surgery using paravertebral block and general anesthesia.
      BACKGROUND: General anesthesia is currently the standard technique used for
      surgical treatment of breast cancer. Increasing hospital costs have focused
      attention on reducing the length of hospital stay for these patients. However,
      the side effects and complications of general anesthesia preclude ambulatory
      surgery for most patients undergoing breast surgery. In April 1994, the authors
      initiated the use of paravertebral block anesthesia for patients undergoing
      primary breast cancer surgery. A review of our early experience revealed that
      this regional anesthetic technique enables effective anesthesia for operative
      procedures of the breast and axilla, reduces postoperative nausea and vomiting,
      and provides prolonged postoperative sensory block that minimizes narcotic
      requirements. METHODS: A retrospective analysis of 145 consecutive patients
      undergoing 156 breast cancer operations using paravertebral block and 100
      patients undergoing general anesthesia during a 2-year period was performed.
      Anesthetic effectiveness and complications, inpatient experience with
      postoperative pain, nausea, vomiting, and length of stay were measured. RESULTS:
      Surgery was successfully completed in 85% of the cases attempted by using
      paravertebral block alone, and in 91% of the cases, surgery was completed by
      using paravertebral block supplemented with local anesthetic. There was a 2.6%
      incidence of complications associated with block placement. Twenty percent of
      patients in the paravertebral group required medication for nausea and vomiting
      during their hospital stay compared with 39% in the general anesthesia group.
      Narcotic analgesia was required in 98% of general anesthesia patients, as opposed
      to 25% of patients undergoing paravertebral block. Ninety-six percent of patients
      having paravertebral block anesthesia were discharged within the day of surgery,
      compared with 76% of patients who had a general anesthetic. CONCLUSIONS:
      Paravertebral block can be used to perform major operations for breast cancer
      with minimal complications and a low rate of conversion to general anesthesia.
      Paravertebral block markedly improves the quality of recovery after breast cancer
      surgery and provides the patient with the option of ambulatory discharge.

PMID- 9563537
TI  - Breast conservation for mammographically occult carcinoma.
AB  - OBJECTIVE: Preoperative mammography is an essential part of the evaluation of
      patient eligibility for breast conserving therapy. SUMMARY BACKGROUND DATA: It is
      uncertain whether factors that contribute to the nonvisualization of carcinoma on
      mammograms are indications for mastectomy. The purpose of this study was to
      determine if the failure to identify clinically evident carcinoma on a mammogram
      is a contraindication to breast conserving therapy. METHODS: An analysis of 268
      women with 269 clinically evident carcinomas who were treated from June 1988 to
      September 1993 was performed. Contraindications to breast preservation included
      multicentric tumors, diffuse indeterminate microcalcifications, pregnancy, prior
      irradiation to the breast region, the inability to achieve negative margins after
      two surgical procedures, and a large tumor to breast ratio. RESULTS:
      Mammographically occult tumors (MO) were present in 52 patients (19%). The mean
      age of patients with MO tumors was 52 versus 57 for mammographically evident (ME)
      tumors (p = 0.009), but the incidence by decade did not vary. Special histologic
      tumor types were more frequent among MO than ME tumors (13.5% vs. 1.8%, p <
      0.001). Tumor size, the incidence of axillary node metastases, and stage did not
      vary. An equal proportion of patients with MO and ME tumors were candidates for
      breast preservation (67% vs. 70%), and a large tumor to breast ratio was the most
      common contraindication in both groups. CONCLUSIONS: Even with modem mammographic
      technology, MO tumors remain a significant problem. This study did not
      demonstrate an association between MO tumors and factors such as size,
      unfavorable histology, or multicentricity which would preclude the use of breast
      conserving therapy. These results support the treatment of MO tumors with breast
      conserving surgery after a detailed clinical evaluation.

PMID- 9563538
TI  - Effect of leucine 13-motilin (KW5139) on early gastric stasis after pylorus
      preserving pancreatoduodenectomy.
AB  - OBJECTIVE: To test a hypothesis that exogenously administered motilin would
      improve early gastric stasis after pylorus-preserving pancreatoduodenectomy
      (PPPD). SUMMARY BACKGROUND DATA: Prolonged gastric stasis is a frequent
      complication after PPPD. We demonstrated that this might at least in part be
      attributable to delayed recovery of phase III activity of the gastric migrating
      motor complex due to low concentrations of plasma motilin caused by resection of
      the duodenum. METHODS: Ten patients with a mean age of 54 years (range, 33-70)
      who underwent PPPD were studied. An assembly of manometric tubes was placed in
      the gastric antrum and jejunum (neoduodenum) at surgery. A gastrostomy tube was
      added for drainage and volume measurements of the gastric juice. After baseline
      recording, saline as a placebo was given intravenously on day 14 and 0.5
      microg/kg of KW5139 (leucine-13 motilin) was given on days 17 and 18 every 2
      hours, 6 times a day. The daily volume of gastric juice output and a gastric
      motility index were measured. RESULTS: The mean period until the first appearance
      of phase III activity in the stomach was 41 +/- 2 days. The injection of saline
      did not change the gastric motility index (7.3 +/- 1.1 to 7.1 +/- 1.3 mmHg; p =
      0.72). In contrast, motilin resulted in a significant increase in the gastric
      motility index (7.5 +/- 1.0 to 17.7 +/- 2.0 mmHg; p < 0.001). The saline
      injection produced no change in the daily gastric juice output (1175 +/- 140 to
      1393 +/- 193 mL; p = 0.09). Motilin significantly decreased the gastric juice
      output (1387 +/- 157 to 934 +/- 142 mL; p = 0.01). CONCLUSIONS: These data
      indicate that KW5139 is a safe and effective prokinetic drug for the treatment of
      early gastric stasis after PPPD.

PMID- 9563539
TI  - Outcome of 67 patients with hepatocellular cancer detected during screening of
      1125 patients with chronic hepatitis.
AB  - OBJECTIVE: We performed this prospective screening trial in chronic hepatitis
      virus-infected patients to determine the incidence of hepatocellular cancer (HCC)
      and the resectability and long-term survival rates of these HCC patients. SUMMARY
      BACKGROUND DATA: Chronic hepatitis B or C virus infection is a major etiologic
      factor in human HCC. It is not clear if routine screening of chronic viral
      hepatitis patients improves the survival of patients who develop HCC. METHODS:
      Screening for HCC was offered to patients chronically seropositive (>5 years) for
      hepatitis B or C infection. All patients underwent percutaneous core liver biopsy
      to assess the histologic severity of chronic liver injury. Patients were screened
      initially and every 3 months thereafter with serum alpha-fetoprotein and
      transabdominal ultrasound evaluations; HCC was confirmed by needle biopsy of
      liver tumors. RESULTS: Screening was performed on 1125 hepatitis-positive
      patients (804 with hepatitis C, 290 with hepatitis B, 31 with both). On liver
      biopsy, 800 patients had mild chronic active hepatitis and 325 had severe chronic
      active hepatitis, cirrhosis, or both. Initial screening detected HCC in 61
      patients. HCC was detected in six more patients during follow-up; thus, the
      incidence of HCC was 5.9% (67/1125). However, 66 of the 67 HCC cases (98.5%)
      arose in the 325 patients with severe chronic active hepatitis or cirrhosis
      (66/325 [20.3%] vs. 1/800 [0.1%], p < 0.0001 [Wilcoxon signed rank]). Median
      follow-up of the 67 HCC patients was 24 months. Locally advanced or metastatic,
      unresectable HCC occurred in 43 patients (64.2%); 24 patients (35.8%), including
      the 6 patients detected during follow-up screening, underwent margin-negative
      resection. The median survival for the 24 resected patients was 26 months,
      compared to 6 months for the 43 patients with unresectable cancer (p < 0.0001,
      Wilcoxon signed rank). CONCLUSIONS: HCC was found to arise in 20.3% of patients
      with chronic hepatitis B or C infection and severe liver injury. Initial
      screening detected resectable lesions in less than half the HCC patients. Routine
      screening of chronic hepatitis B or C virus-infected patients with ultrasound and
      alpha-fetoprotein determination should be reserved for patients with severe
      chronic active hepatitis, cirrhosis, or both.

PMID- 9563540
TI  - Induction of long-term remission in advanced hepatocellular carcinoma with
      percutaneous isolated liver chemoperfusion.
AB  - OBJECTIVE: The aim of this study was to report the long-term results of
      percutaneous isolated liver chemoperfusion with hepatic venous isolation and
      charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced
      hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The results of
      conventional chemotherapy including regional and systemic chemotherapy in
      patients with HCC remain dismal, and long-term survivors after treatment are rare
      among patients with multiple advanced HCC. In an effort to improve this
      situation, we previously developed a novel system of percutaneous isolated liver
      chemoperfusion with HVI-CHP. METHODS: Doxorubicin (60 to 150 mg/m2) was
      administered via the hepatic artery, under conditions of extracorporeal drug
      elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total
      treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished
      mainly by the single catheter technique using a newly developed 4-lumen-balloon
      catheter, which was used to isolate and capture total hepatic venous outflow and,
      at the same time, to direct the filtered blood to the right atrium. RESULTS:
      Complete remission was achieved in five patients, of which four received repeated
      treatments (two or three times). Although 1 of 5 patients with complete remission
      died of pulmonary metastases at 8 months, the other 4 remain healthy and free of
      disease at 20, 24, 27, and 42 months after the first treatment. Partial responses
      were observed in 12 patients. Duration of response in responders (complete and
      partial) with repeated treatments was significantly longer than that with a
      single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method
      was 39.7% at 5 years. The treatments were well-tolerated, and the primary side
      effects were mild to moderate chemical hepatitis and reversible myelosuppression.
      CONCLUSIONS: The results suggest that percutaneous isolated liver chemoperfusion
      with HVI-CHP is an effective palliative treatment in the majority of patients and
      yields long-term complete remission in some patients with multiple advanced HCC.

PMID- 9563541
TI  - Laparoscopy and laparoscopic ultrasonography avoid exploratory laparotomy in
      patients with hepatocellular carcinoma.
AB  - OBJECTIVE: This prospective study evaluates the value of laparoscopy and
      laparoscopic ultrasonography (USG) in avoiding exploratory laparotomy in patients
      with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Laparotomy and
      intraoperative USG is the gold standard to determine the resectability of HCC. No
      palliation can be offered to patients found to have unresectable disease, and the
      surgical exploration causes morbidity. METHODS: From June 1994 to June 1996, 110
      of 370 patients (30%) with HCC were considered candidates for possible hepatic
      resection. Preoperative liver function was assessed using Child-Pugh grading and
      indocyanine green retention test. The extent of disease was evaluated with
      radiologic studies, including percutaneous USG, computerized tomography scan, and
      hepatic angiogram. Nineteen patients were excluded from the study because of
      previous upper abdominal surgery (n = 12), ruptured tumors (n = 4), refusal by
      patients (n = 2), and instrument failure (n = 1). Laparoscopy and laparoscopic
      USG was performed on 91 patients immediately before a planned laparotomy aiming
      at hepatic resection. Laparotomy was aborted when definite evidence of
      unresectable disease was found on laparoscopic examination. RESULTS: The median
      time required for laparoscopy and laparoscopic USG was 30 minutes (range, 10 to
      120 minutes). Fifteen patients had evidence of unresectable disease on
      laparoscopic examination. Among the remaining 76 patients who underwent
      laparotomy, 9 had exploration only and 67 underwent hepatic resection. Thus,
      exploratory laparotomy was avoided in 63% of patients with unresectable disease.
      The laparoscopic examination failed to confirm unresectable disease more often
      when the tumor was >10 cm in diameter. The procedure accurately assessed the
      adequacy of the liver remnant and the presence of intrahepatic metastases, but it
      was less sensitive in determining the presence of tumor thrombi in major vascular
      structures and the extent of invasion of adjacent organs. When unresectable
      disease was detected without the need for a laparotomy, the postoperative
      recovery was faster, and the nonoperative treatment for the tumor could be
      initiated earlier. CONCLUSIONS: Laparoscopy with laparoscopic USG avoids
      unnecessary laparotomy in patients with HCC and should precede a planned
      laparotomy aiming at hepatic resection.

PMID- 9563542
TI  - Differentiated thyroid cancer: determinants of disease progression in patients
      <21 years of age at diagnosis: a report from the Surgical Discipline Committee of
      the Children's Cancer Group.
AB  - OBJECTIVE: This study was done to define the extent of disease and evaluate the
      effect of staging and treatment variables on progression-free survival in
      patients with differentiated thyroid carcinoma who were less than 21 years of age
      at diagnosis. SUMMARY BACKGROUND DATA: Differentiated thyroid cancer in young
      patients is associated with early regional lymph node involvement and distant
      parenchymal metastases. Despite this, the overall long-term survival rate is
      greater than 90%, which suggests that biologic rather than treatment factors have
      a greater effect on outcome. METHODS: Variables analyzed for their impact on
      progression-free survival in a multi-institutional cohort of 329 patients
      included age, antecedent thyroid irradiation, extrathyroidal tumor extension,
      size, nodal involvement, distant metastases, technique of thyroid surgery and
      lymphatic dissection, initial treatment with 131Iodine, residual cervical
      disease, and histopathologic subtype. Surgical complications were correlated with
      the specific procedures completed on the thyroid gland or cervical lymphatics.
      RESULTS: The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at
      10 years with 2 disease-related deaths. Regional lymph node and distant
      metastases were present in 74% and 25% of patients, respectively. Progression
      free survival was less in younger patients (p = 0.009) and those with residual
      cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was
      more frequent after total or subtotal thyroidectomy (p = 0.001) while wound
      complications increased after radical neck dissections (p < 0.00001).
      CONCLUSIONS: The progression-free survival rate was better after a complete
      resection and in older patients. Progression-free survival rate was the same
      after lobectomy or more extensive thyroid procedures, but comparison was
      confounded by the increased use of total or subtotal thyroidectomy in patients
      with advanced disease. The risk of permanent hypocalcemia increased when total or
      subtotal thyroidectomy was done. Thyroid lobectomy alone may be appropriate for
      patients with small localized lesions while total or subtotal thyroidectomy
      should be considered for more extensive tumors.

PMID- 9563543
TI  - Hurthle cell neoplasms of the thyroid: are there factors predictive of
      malignancy?
AB  - OBJECTIVE: To determine if any preoperative or intraoperative factors can
      reliably predict malignancy in patients with Hurthle cell neoplasms. SUMMARY
      BACKGROUND DATA: Most experienced surgeons recommend total thyroidectomy for
      Hurthle cell carcinomas and reserve thyroid lobectomy for Hurthle cell adenomas.
      However, delineation between Hurthle cell adenoma versus carcinoma often cannot
      reliably be made either before or during surgery. METHODS: Medical records from
      57 consecutive patients who underwent thyroid resections for Hurthle cell
      neoplasms between October 1984 and April 1995 at The Johns Hopkins Hospital were
      analyzed to determine if any factors were predictive of malignancy. RESULTS: Of
      the 57 patients with Hurthle cell neoplasms, 37 had adenomas and 20 had
      carcinomas, resulting in a 35% prevalence of malignancy. Patients with adenomas
      did not differ from those with carcinoma with respect to age, sex, or history of
      head and neck irradiation. However, patients with Hurthle cell carcinomas had
      significantly larger tumors (4.0 +/- 0.4 cm vs. 2.4 +/- 0.2 cm, p < 0.005).
      Furthermore, although the incidence of malignancy was only 17% for tumors 1 cm or
      less and 23% for tumors 1 to 4 cm, tumors 4 cm or greater were malignant 65% of
      the time (p < 0.05). Both fine-needle aspiration and intraoperative frozen
      section analysis had low sensitivities in the detection of cancer (16% and 23%,
      respectively). With up to 9 years of follow-up, there has been no tumor-related
      mortality. CONCLUSIONS: These data demonstrate that the size of a Hurthle cell
      neoplasm is predictive of malignancy. Therefore, at the time of initial
      exploration for large Hurthle cell neoplasms (>4 cm), definitive resection
      involving both thyroid lobes should be considered because of the higher
      probability of malignancy.

PMID- 9563544
TI  - Clinical impact of abnormal gut flora in infants receiving parenteral nutrition.
AB  - OBJECTIVE: Illness is associated with the carriage of abnormal flora (aerobic
      Gram-bacilli except E. coli) in the oropharynx and rectum. The aim of this study
      was to investigate whether carriage of abnormal flora is associated with
      increased risk of sepsis and septicemia in surgical newborn infants. METHODS: A 2
      year prospective study was carried out on 94 consecutive newborn infants
      requiring parenteral nutrition (PN) for gastrointestinal abnormalities. Throat
      and rectal swabs were taken on day 1 of PN and twice weekly. Patients were
      divided into two groups: abnormal flora (AF; n = 41) and normal flora (NF; n =
      53). Sepsis was defined as clinical features of generalized inflammation
      requiring blood culture. Septicemia was the combination of sepsis and positive
      blood culture. RESULTS: Among the infants carrying abnormal flora Pseudomonas and
      Enterobacter spp. predominated. Duration of PN (AF median 30 days; NF median 9
      days), incidence of sepsis (AF 29%; NF 6%), and septicemia (AF 22%; NF 2%) were
      significantly greater in the group of infants with abnormal flora. Surveillance
      cultures allow the detection of a subset of infants on PN at high risk of sepsis
      and septicemia. The degree of gut dysfunction related to the severity of
      underlying disease determines the duration of PN and the development of abnormal
      flora. The association between abnormal carriage and increased risk of sepsis and
      septicemia may be because of the intestinal endotoxin pool known to cause liver
      impairment and consequent suppression of systemic immunity.

PMID- 9563545
TI  - Pediatric wound infections: a prospective multicenter study.
AB  - OBJECTIVE: Surgical wound infections remain a significant source of postoperative
      morbidity. This study was undertaken to determine prospectively the incidence of
      postoperative wound infections in children in a multi-institutional fashion and
      to identify the risk factors associated with the development of a wound infection
      in this population. SUMMARY BACKGROUND DATA: Despite a large body of literature
      in adults, there have been only two reports from North America concerning
      postoperative wound infections in children. METHODS: All infants and children
      undergoing operation on the pediatric surgical services of three institutions
      during a 17-month period were prospectively followed for 30 days after surgery
      for the development of a wound infection. RESULTS: A total of 846 of 1021
      patients were followed for 30 days. The overall incidence of wound infection was
      4.4%. Factors found to be significantly associated with a postoperative wound
      infection were the amount of contamination at operation (p = 0.006) and the
      duration of the operation (p = 0.03). Comparing children who developed a wound
      infection with those who did not, there were no significant differences in age,
      sex, American Society of Anesthesiologists (ASA) preoperative assessment score,
      length of preoperative hospitalization, location of operation (intensive care
      unit vs. operating room), presence of a coexisting disease or remote infection,
      or the use of perioperative antibiotics. CONCLUSIONS: Our results suggest that
      wound infections in children are related more to the factors at operation than to
      the overall physiologic status. Procedures can be performed in the intensive care
      unit without any increase in the incidence of wound infection.

PMID- 9563546
TI  - Radiofrequency ablation of porcine liver in vivo: effects of blood flow and
      treatment time on lesion size.
AB  - OBJECTIVE: To determine, in vivo, the effect of radiofrequency ablation (RFA)
      treatment time and tissue blood flow on the size and shape of the resulting
      necrotic lesion in porcine liver. SUMMARY BACKGROUND DATA: Radiofrequency
      ablation is an electrosurgical technique that uses a high frequency alternating
      current to heat tissues to the point of desiccation (thermal coagulation).
      Radiofrequency ablation is well established as the treatment of choice for many
      symptomatic cardiac arrhythmias because of its ability to create localized
      necrotic lesions in the cardiac conducting system. Until recently, a major
      limitation of RFA was the small lesion size created by this technique.
      Development of bipolar and multiple-electrode RFA probes has enabled the creation
      of larger lesions and therefore has expanded the potential clinical applications
      of RFA, which includes the treatment of liver tumors. A basic understanding of
      factors that influence RFA lesion size in vivo is critical to the success of this
      treatment modality. The optimal RFA technique, which maximizes liver lesion size,
      has yet to be determined. Theoretically, lesion size varies directly with time of
      application of the RF current, and inversely with blood flow, but these
      relationships have not been previously studied in the liver. METHODS: Six animals
      underwent hepatic RFA (460 kHz), for 5, 7.5, 10, 12.5, 15, and 20 minutes.
      Identical, predetermined anatomic areas of the liver were ablated in each animal.
      Two additional animals underwent 12 RFA treatments -- 6 with vascular inflow
      occlusion (Pringle maneuver) and 6 with uninterrupted hepatic blood flow. Animals
      were euthanized and the livers were removed for gross pathologic examination. All
      lesions were measured in three dimensions and photographed. Tissues were examined
      by routine histology and by histochemistry to determine viability. RESULTS:
      Increasing duration of RFA application from 5 through 20 minutes did not create
      lesions of larger diameter, but this time increase did predict deeper lesion
      production (beta = 0.34, p = 0.04). A range of lesion shapes were created from
      four separate ovals (corresponding to each electrode), to larger ovals
      intersecting to form a cross, to spheroid lesions. The number of blood vessels in
      close proximity to the probe tip (within a 1-cm radius from the center of the
      lesion) strongly predicted minimum lesion diameter (beta = -0.61, p = 0.0001) and
      lesion volume (beta = -0.56, p = 0.0004). This negative effect of blood flow on
      lesion size was confirmed experimentally. Radiofrequency ablation lesions created
      during a Pringle maneuver were significantly larger in all three dimensions than
      lesions created without a Pringle maneuver: minimum diameter was 3.0 cm (with
      Pringle) versus 1.2 cm (p = 0.002), maximum diameter was 4.5 cm (with Pringle)
      versus 3.1 cm (p = 0.002), depth was 4.8 cm (with Pringle) versus 3.1 cm (p <
      0.001), and lesion volume was 35.0 cm3 (with Pringle) versus 6.5 cm3 (p < 0.001).
      CONCLUSIONS: Blood flow is a strong predictor of all RFA lesion dimensions in
      porcine liver in vivo, whereas a change of treatment time from 5 to 20 minutes is
      predictive only of lesion depth, but not diameter or volume.

PMID- 9563547
TI  - Surgical margin in hepatic resection for colorectal metastasis: a critical and
      improvable determinant of outcome.
AB  - OBJECTIVE: To update the analysis of technical and biologic factors related to
      hepatic resection for colorectal metastasis in a large single-institution series
      to identify important prognostic indicators and patterns of failure. SUMMARY
      BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the
      liver is the only potentially curable treatment. Careful patient selection of
      those with resectable liver-only metastatic disease is crucial to the success of
      surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing
      curative hepatic resection for metastatic colorectal carcinoma were analyzed
      retrospectively. Variables examined included sex, stage of primary lesion, size
      of liver lesion(s), number of lesions, disease-free interval, ploidy,
      differentiation, preoperative carcinoembryonic antigen level, and operative
      factors such as resection margin, use of cryotherapy, intraoperative ultrasound,
      and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic
      antigen (CEA) levels significantly control prognosis. Patients with only one or
      two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year
      disease-free survival rate of more than 30%. Disease-free interval, original
      stage, bilobar involvement, size of metastasis, differentiation, and ploidy were
      not significant predictors of recurrence. The pattern of failure correlates with
      surgical margin. Routine use of intraoperative ultrasound resulted in an
      increased incidence of negative surgical margin during the period examined.
      CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from
      colorectal cancer is safe and curable in appropriately selected patients.
      Biologic factors, such as number of lesions and carcinoembryonic antigen levels,
      determine potential curability, and surgical margin governs the patterns of
      failure and outcome in potentially curable patients. Optimization of selection
      criteria and surgical resection margins will improve outcome.

PMID- 9563548
TI  - Severe acute respiratory distress syndrome secondary to acute pancreatitis
      successfully treated with extracorporeal membrane oxygenation in three patients.
AB  - OBJECTIVE: To review three patients who underwent extracorporeal membrane
      oxygenation (ECMO) for acute respiratory failure secondary to pancreatitis.
      SUMMARY BACKGROUND DATA: Severe acute pancreatitis often causes the acute
      respiratory distress syndrome (ARDS), and if ventilation is required, the
      mortality rate is more than 50%. If the ratio of PaO2/FiO2 falls below 100 mm Hg
      or the Murray lung injury score exceeds 3.5, the mortality rate rises to more
      than 80%. Three patients who have severe ARDS secondary to pancreatitis, who were
      hypoxic despite ventilation with 100% oxygen and high airway pressures, and who
      were all successfully treated with ECMO are reported here. The consensus here is
      that all three patients would have died without ECMO. METHODS: Retrospective
      chart review and discussion of the literature. RESULTS: Pre-ECMO data: mean
      PaO2/FiO2 59.3 mm Hg, mean Murray lung injury score 3.7, one patient administered
      20 ppm inhaled nitric oxide. ECMO data: mean extracorporeal flow at initiation of
      ECMO 56.3 mL/kg per minute, all patients administered veno-venous ECMO, mean
      duration of ECMO 104.7 hours. All patients were successfully weaned from ECMO and
      extubated. One patient had a protracted hospital stay because of a colo-cutaneous
      fistula. All patients are long-term survivors. CONCLUSIONS: Extracorporeal
      membrane oxygenation proved an effective therapy for severe ARDS complicating
      acute pancreatitis. Extracorporeal membrane oxygenation was conducted without
      bleeding complications in these three patients.

PMID- 9563549
TI  - Halofuginone--an inhibitor of collagen type I synthesis--prevents postoperative
      formation of abdominal adhesions.
AB  - OBJECTIVE: To evaluate the effects of halofuginone, a specific inhibitor of
      collagen type I synthesis, on the postoperative formation of abdominal adhesions
      in rats. SUMMARY BACKGROUND DATA: Postoperative adhesions remain the leading
      cause of small bowel obstruction in the Western world. Surgical trauma causes the
      release of a serosanguineous exudate that forms a fibrinous bridge between two
      organs. This becomes ingrown with fibroblasts, and subsequent collagen deposition
      leads to the formation of a permanent adhesion. Most of the drugs used have been
      clinically ineffective, and none has been specific to a particular extracellular
      matrix molecule. Therefore, there are serious concerns about the toxic
      consequences of interfering with the biosynthesis of other collagens, other
      matrix proteins, or vital collagen-like molecules. METHODS: Adhesions were
      induced by scraping the cecum until capillary bleeding occurred. The adhesions
      were scored 21 days later. Halofuginone was either injected intraperitoneally (1
      microg/25 g body weight) every day, starting on the day of operation, or added
      orally at concentrations of 5 or 10 mg/kg, starting 4 days before the operation.
      Collagen alpha1(I) gene expression was evaluated by in situ hybridization, total
      collagen was estimated by Sirius red staining, and collagen type III was detected
      by immunohistochemistry. RESULTS: The adhesions formed between the intestinal
      walls were composed of collagen and were populated with cells expressing the
      collagen alpha1(I) gene. Regardless of the administration procedure, halofuginone
      significantly reduced the number and severity of the adhesions. Halofuginone
      prevented the increase in collagen alpha1(I) gene expression observed in the
      operated rats, thus reducing collagen content to the control level. In
      fibroblasts derived from abdominal adhesions, halofuginone induced dose-dependent
      inhibition of collagen alpha1(I) gene expression and collagen synthesis. Collagen
      type III levels were not altered by adhesion induction or by halofuginone
      treatment. CONCLUSIONS: Upregulation of collagen synthesis appears to have a
      critical role in the pathophysiology of postoperative adhesions. Halofuginone, an
      inhibitor of collagen type I synthesis, could be used as an important tool in
      understanding the role of collagen in adhesion formation, and it may become a
      novel and promising antifibrotic agent for preventing postoperative adhesion
      formation.

PMID- 9563550
TI  - Biliary atresia-polysplenia syndrome: surgical and clinical relevance in liver
      transplantation.
AB  - OBJECTIVE: To review a single center's 10-year experience with liver
      transplantation (LTx) for the biliary atresia-polysplenia syndrome (BA-PS) and to
      define surgical and clinical guidelines for its management. SUMMARY BACKGROUND
      DATA: BA is the most common indication for pediatric liver transplantation (LTx)
      and is associated with PS in 12% of cases. Only a few studies of LTx for BA-PS
      have been reported, and the optimal management of BA-PS patients undergoing LTx
      has yet to be determined. METHODS: From July 1985 to September 1995, 166 liver
      transplants were performed in 130 patients with BA and were included in the
      study. The malformations most commonly associated with BA-PS, surgical techniques
      used to overcome these anomalies, and surgical pitfalls that could have
      contributed to the outcome were characterized. Actuarial 10-year patient and
      graft survival for patients undergoing LTx for BA-PS were calculated and compared
      to those with isolated BA. RESULTS: Ten patients (7.8%) with BA had associated
      PS. An additional patient with PS without BA was included in the study. The
      diagnosis of PS was unknown before the transplantation in 72% of cases. Thirteen
      liver transplants were performed in these 11 patients. Modifications of the usual
      surgical technique were used to overcome the complex anatomy encountered. There
      was no association between the type of anomaly and the outcome, nor were there
      any significant differences in patient survival (72% vs. 73.5%, p = 0.79) or
      graft survival (56.4% vs. 54.6%, p = 0.54). CONCLUSIONS: The association of BA
      with various anomalies should be considered a spectrum that may vary widely from
      patient to patient. The finding of two or more of these malformations in a
      patient awaiting transplantation should lead the surgeon to look systematically
      for other associated anomalies. With some special surgical considerations, the
      outcome in BA-PS patients should not differ from those with isolated BA.

PMID- 9563551
TI  - Guidelines for surgical procedures after liver transplantation.
AB  - OBJECTIVE: The first purpose of this study is to identify the types and
      incidences of surgical procedures in patients who have previously undergone liver
      transplantation, with particular focus on the complication rates and the lengths
      of hospital stay. The second purpose is to present the management guidelines for
      patients with liver transplants at the preoperative, intraoperative, and
      postoperative stages of surgical procedure. SUMMARY BACKGROUND DATA: The surgical
      literature on this issue is scant, and with the growing liver transplant patient
      population it is not unlikey for any surgery specialist to have to operate on a
      patient who has undergone liver transplantation. METHODS: A sample of 409
      patients with available hospital records, with a minimum of a 2-year follow-up,
      and with telephone access for interviews was chosen. Type of surgery, time from
      the liver transplant, hospital stay, immunosuppressive regimen, and complications
      were recorded. RESULTS: A large proportion of patients (24.2%) underwent some
      type of surgical procedure 2 to 10 years after liver transplantation. The authors
      demonstrate that most of the elective procedures can be safely carried out
      without an increased incidence of complication and without longer hospital stay
      than the general population. Conversely, emergent procedures are plagued by a
      greater incidence of complications that not only affect the function of the liver
      graft but may risk the life of the patient.

PMID- 9563552
TI  - Conversion of failed transjugular intrahepatic portosystemic shunt to distal
      splenorenal shunt in patients with Child A or B cirrhosis.
AB  - OBJECTIVE: The authors demonstrate the feasibility of converting failed
      transjugular intrahepatic portosystemic shunt (TIPS) to distal splenorenal shunt
      (DSRS) in patients with good hepatic reserve for long-term control of variceal
      bleeding. SUMMARY BACKGROUND DATA: TIPS is an effective method for decompressing
      the portal venous system and controlling bleeding from esophageal and gastric
      varices. TIPS insufficiency is, however, a common problem, and treatment
      alternatives in patients with an occluded TIPS are limited because most have
      already failed endoscopic therapy. METHODS: The records of five patients who
      underwent conversion from TIPS to DSRS because of TIPS failure or complication in
      the past 36 months were reviewed. RESULTS: Four patients had ethanol-induced
      cirrhosis and one patient had hepatitis C virus cirrhosis. Three patients were
      Child-Pugh class A and two were class B. All patients had excellent liver
      function, with galactose elimination capacities ranging from 388 to 540 mg/min
      (normal 500 +/- 100 mg/min). The patients had TIPS placed for acute (2) or
      sclerotherapy-resistant (3) variceal hemorrhage. All five TIPS stenosed 3 to 23
      months after placement, with recurrent variceal hemorrhage and failed TIPS
      revision. One patient had stent migration to the superior mesenteric vein that
      was removed at the time of DSRS. All five patients underwent successful DSRS, and
      none have had recurrent hemorrhage 18 to 36 months after surgery. CONCLUSIONS:
      TIPS provides inadequate long-term therapy for some Child-Pugh A or B patients
      with recurrent variceal hemorrhage. TIPS failure in patients with good liver
      function can be salvaged by DSRS in many cases.

PMID- 9563553
TI  - Treating patients with myasthenia gravis.

PMID- 9563554
TI  - Evaluation of the degree of splenic injury by both CT and US in pediatric trauma
      victims.

PMID- 9563555
TI  - Bilateral adrenalectomy for Cushing's syndrome.

PMID- 9563556
TI  - Recent advances in the treatment of patients with malignant melanoma.

PMID- 9563557
TI  - Clinical audit at the heart of clinical effectiveness.
AB  - Clinical audit is becoming an increasingly sophisticated process now practised by
      a majority of clinicians. A crucial tool enabling clinicians to improve their
      care, it involves structured review against agreed standards. Clinical audit is a
      key component of each of the elements of clinical effectiveness enabling health
      care interventions to achieve what is intended in the most beneficial way. A
      national lead in the development and integration of clinical audit into everyday
      practice is provided in England, with Department of Health support, by the
      professional bodies responsible for setting and maintaining clinical standards.
      The Department of Health recently published a White Paper setting out Government
      intentions for a greater focus on quality in health. Included in these plans is a
      National Institute for Clinical Excellence to support and coordinate national
      clinical guideline and clinical audit development programmes, as well as a
      greater focus on the quality, effectiveness and outcomes of care.

PMID- 9563558
TI  - Quality in obstetrics and gynaecology: the example of the enquiries into maternal
      mortality.
AB  - For nearly 50 years there has been an independent system for monitoring all
      maternal deaths in the United Kingdom. Validation exercises suggest that about
      99% of cases are successfully identified and reviewed. The analysis is published
      every 3 years and includes independent assessment as to whether substandard care
      was present. As the proportion of cases where substandard care is present remains
      constant at about 40-50%, it is claimed that these reports do little to improve
      the quality of care. Review of particular causes of deaths suggests that the
      regular stating of the problem areas, developing management guidelines relating
      to these, and re-auditing practice, almost certainly has improved standards.
      However, more remains to be done.

PMID- 9563559
TI  - The history and achievements of the National Confidential Enquiry into
      Perioperative Deaths.
AB  - The National Confidential Enquiry into Perioperative Deaths started in 1989 as a
      direct development of a Confidential Enquiry in the United Kingdom in 1984.
      Different samples from the 20,000 deaths in hospital within 30 days of a surgical
      operation are selected each year. Questionnaires about these are examined by
      groups of anaesthetists and surgeons, and lessons about the quality of
      perioperative care are derived. Causation is not emphasized but examples of
      potential for improvement are sought. Changes of consultant practice, increase in
      medical audit, improvement in physiological monitoring, appropriate matching of
      specialist experience to patients' medical conditions and increased awareness of
      the need for critical care areas are believed to have been influenced by this
      unique enquiry.

PMID- 9563560
TI  - Clinical effectiveness for health care quality improvement.
AB  - This paper describes the work of the Research Unit of the Royal College of
      Physicians on clinical effectiveness and links with other national initiatives.
      The overall goal is to improve the quality of care by basing routine care on
      research evidence, an approach referred to as the 'bridge for health'. Systematic
      reviews bring together research evidence and are largely carried out by the
      Cochrane Collaboration, the NHS Centre for Reviews and Dissemination and the NHS
      Health Technology Assessment programme. Clinical guidelines, now produced
      according to a more rigorous methodology, are used to package research to support
      decisions about health care by clinicians, patients and others. Clinical audit,
      along with outcomes development, is carried out at a national level to support
      the implementation of clinical guidelines by clinical teams in local health
      services. To achieve this, it matches the best principles of quality improvement.
      Future identified trends in clinical effectiveness include a greater emphasis on
      better integration of effort and exchange of best practice.

PMID- 9563561
TI  - Clinical audit activities in surgery.
AB  - Large scale audits can attract the participation of the majority of surgeons.
      They require careful planning and must be supported by an infrastructure to co
      ordinate the running of the audit and to ensure accuracy of data. Audits can be
      important sources of information for the development of evidence-based
      guidelines, and this approach is a good strategy for bringing the lessons
      obtained from the audit to the profession. Audits that work closely with
      professional bodies produce the best results and are enhanced by patient
      representation. Risk stratification is an essential component of comparative
      studies and should be incorporated to ensure that multi-centre audits are
      systematic.

PMID- 9563563
TI  - The philosophy of clinical practice guidelines: purposes, problems, practicality
      and implementation.
AB  - There are a number of technical and professional challenges to the use of
      clinical practice guidelines in the United Kingdom. Until recently, many
      guidelines have been consensus-based rather than being explicitly linked to
      evidence of effectiveness and have also been of variable quality. Moreover,
      clarity of purpose has been lacking with some guidelines being developed as a
      means of limiting access to secondary care rather than as a means of assisting
      clinical decision-making. Implementation of new research into practice and of
      clinical practice guideline recommendations shares many of the same barriers to
      changing clinician behaviour. Without local support systems to assist with
      implementation, including clinical audit programmes and methods of feeding back
      information on current practice, it is unlikely that guidelines will change
      practice in the majority of clinicians. Progress on the implementation of
      guidelines in the British National Health Service is discussed.

PMID- 9563562
TI  - Clinical effectiveness in British psychiatry: with a focus on the role of the
      Royal College of Psychiatrists.

PMID- 9563564
TI  - Raising standards in pathology: the accreditation process in the United Kingdom.
AB  - The accreditation scheme established by Clinical Pathology Accreditation (UK) Ltd
      has been in formal operation since 1992. So far, 933 laboratories have been
      inspected, nearly two-thirds of all laboratories in the UK. Of these, 73% are
      fully accredited, 24% have outstanding conditions requiring correction, and 3%
      have been referred. Inspectors have identified some regional and specialty
      differences, most notably in histopathology and cytology. The second cycle of
      inspection visits is underway. Most UK departments of pathology have embraced the
      concept of accreditation with relative enthusiasm and there has been strong
      support from professional bodies, specialist societies, health service managers,
      the independent sector and government departments.

PMID- 9563565
TI  - King's Fund Organisational Audit: more than ticks in boxes.
AB  - This article describes the work of King's Fund Organisational Audit (KFOA), the
      UK's premier accreditation and standards based organizational development
      programme. The article sets the context for the work of organizational audit
      against the recent change to a Labour government, the increased emphasis on
      patient/user involvement and the move towards evidence-based medicine and the
      drive towards clinical outcomes. The article makes a brief comparison between the
      work of KFOA and the Australian Council of Healthcare Standards, and how KFOA is
      developing its accreditation process in collaboration with other bodies. Some of
      the many benefits of organizational audit are discussed using case study
      material.

PMID- 9563566
TI  - The patients' perception of quality in surgery.
AB  - The benefits of measuring patient satisfaction have been increasingly
      acknowledged in recent years. A range of techniques has been used including
      analysis of complaints made by patients and/or relatives, focus group interviews
      following discharge, postal and telephone surveys, face-to-face interviews and
      critical incident analysis. Both quantitative and qualitative methodologies are
      often employed in patient-satisfaction research. It is suggested that a two-tier
      approach of methods can increase validity and reliability (i.e. utilizing
      qualitative approaches in order to develop a quantitative tool). Surgery will
      benefit through the identification of quality benchmarks based on this type of
      research. There must be an emphasis on incorporating the results of patient
      satisfaction studies into practice and the monitoring of improvements based on
      the identified benchmarks.

PMID- 9563567
TI  - Temporal and spatial expression of erbB4 in ectodermal and mesenchymal cells
      during primary palatogenesis in noncleft and cleft strains of mice.
AB  - Primary palatogenesis in mice is similar to that in humans, and spontaneous cleft
      lip appears to be multifactorially determined in both. Binding of a ligand to
      erbB4 has been shown to stimulate the receptor's protein kinase activity, which
      subsequently stimulates a signal-transduction cascade leading to cell growth and
      differentiation, and to morphogenesis during development. In this study, an
      immunohistochemical technique was used to investigate the temporal and spatial
      expression of erbB4 in the primary palate of cleft (A/WySn) and noncleft strains
      of mice (BALB/cBy). Positive staining of erbB4 was found in ectodermal and
      mesenchymal cells of facial prominences before the primary palate formation stage
      (day 10, hour 20) in both strains. During the primary palate formation stage (day
      11, hour 20), positive staining of erbB4 was found in the ectodermal and
      mesenchymal cells of the facial prominences of the noncleft strain, but not in
      those of the cleft strain. These results suggest erbB4 expression may be
      associated with normal primary palatogenesis of mice and, conversely, cleft lip
      may be associated with a deficiency of erbB4 expression during primary palate
      formation in mice.

PMID- 9563568
TI  - Overexpression of c-Src in areas of hyperproliferation in head and neck cancer,
      premalignant lesions and benign mucosal disorders.
AB  - To examine which proteins are responsible for the elevated protein tyrosine
      kinase (PTK) activity in human head and neck squamous cell carcinoma (HNSCC) and
      adjacent histologically normal epithelium, paraffin embedded sections of these
      tissues were stained for PTK c-Src. Using double labeling techniques and
      antibodies against both the proliferation marker Ki-67 and PTK c-Src, we have
      shown that c-Src is overexpressed in areas of hyperproliferation in HNSCC,
      dysplastic epithelium, benign papillomas and inflamed normal tissue. Our data
      indicate that c-Src is (one of) the protein(s) responsible for the increased PTK
      activity in HNSCC. We could not demonstrate that c-Src expression is responsible
      for the increased PTK activity in normal epithelium adjacent to tumour tissue. We
      assume that c-Src plays a role in the increased proliferation seen in
      (pre)malignant and benign epithelial lesions as well as in reactive inflammatory
      epithelial hyperplasia.

PMID- 9563569
TI  - Argyrophilic nucleolar organizer regions (AgNORs) in ameloblastomas and
      adenomatoid odontogenic tumours (AOTs).
AB  - Twenty-two cases of ameloblastoma and ten cases of adenomatoid odontogenic tumour
      (AOT) were analyzed comparatively by the AgNOR technique. Ameloblastomas were
      distributed into three groups according to their clinical behaviour: primary
      lesions without recurrences (PLWTR), 5 cases; primary lesions with recurrences
      (PLWR), 4 cases; and recurrences, 13 cases. The cases were also regrouped
      according to their histological pattern: follicular (9 cases), plexiform (7
      cases), acanthomatous (4 cases) and unicystic (2 cases). Considering histological
      patterns, there was a significant statistical difference only between follicular
      and plexiform types. There were no significant differences between the group of
      ameloblastomas and the group of AOTs or between the three groups of
      ameloblastomas with different clinical behaviour. Our results strongly suggest
      that the distinct clinical behaviour of ameloblastomas and AOT is not correlated
      with their cellular proliferation ratio. Thus, the infiltrative ability of the
      ameloblastomas is probably not related to the cellular proliferation index of
      these tumours.

PMID- 9563570
TI  - Characterization of an amorphous deposit in the lamina propria in oral snuff
      users in the Sudan as collagen.
AB  - Histological and ultrastructural features of 25 oral snuff dipper's lesions with
      distinctive subepithelial hyaline deposits were investigated. Periodic acid
      Schiff reaction with and without diastase digestion demonstrated the presence of
      glycogen and other carbohydrates, but histochemical stains for normal collagen,
      elastin and fibrin showed a weak variable reactivity of the deposit. Although in
      7/25 cases the deposit was in close proximity to labial salivary glands and on
      occasions ducts were found within the deposit, the presence of mucin was not a
      consistent feature. Congo red staining and immunohistochemical investigation with
      an anti-amyloid antibody did not support the previous contention that such
      deposits were amyloid in nature. Immunohistochemically, collagen antibodies also
      provided negative results, but ultrastructural features of three biopsies studied
      suggest that the bulk of this deposit is made up of collagen, as typical cross
      striated fibrils were found. The pathogenesis of this deposit could therefore be
      interpreted as over-production and/or reduced turnover of collagen by resident
      fibroblasts, which is further altered by the ingredients of toombak. The deposit
      does not appear to be a secretory product.

PMID- 9563571
TI  - Associations between mast cells and laminin in oral lichen planus.
AB  - Mast cell numbers are increased significantly in oral lichen planus (OLP). In
      other inflammatory conditions, mast cells frequently adhere to extracellular
      matrix proteins such as laminin. The aim of this study, therefore, was to
      determine whether the distribution of mast cells in OLP is related
      topographically to laminin in vascular and epithelial basement membranes.
      Monoclonal antibodies for tryptase, laminin and the alpha6beta1 CD49f laminin
      binding integrin were used to identify mast cells, basement membranes (blood
      vessels and basal epithelium) and the "classical" laminin adhesion receptor,
      respectively. A double-labelling immunoperoxidase technique was employed to
      examine and compare mast cell-laminin relationships in OLP (n=19) and normal
      buccal mucosa (NBM, n=13). In both OLP and NBM, the majority of mast cells were
      located close to vascular basement membranes. Quantitative studies revealed that
      the number of mast cells associated with the laminin of vascular basement
      membranes (distance <1 microm) was two-fold and three-fold higher, respectively,
      in the superficial and deep layers in OLP compared with NBM (P<0.001). The
      frequency distribution of mast cells associated with basal epithelium was not
      statistically different in both groups (P>0.05). The association of mast cells
      with laminin may be an important determinant of mast cell density in OLP During
      OLP lesion formation and progression, the preferential distribution of mast cells
      in the immediate perivascular region provides an ideal situation for mast cell
      derived mediators to influence the vascular endothelium.

PMID- 9563572
TI  - Preliminary evidence for an association of Epstein-Barr virus with pre-ulcerative
      oral lesions in patients with recurrent aphthous ulcers or Behcet's disease.
AB  - In this study we used the polymerase chain reaction (PCR), slot blot and Southern
      blot hybridization, direct sequencing and in situ hybridization (ISH) to show the
      possible presence of EBV-DNA in pre-ulcerative oral aphthous lesions of patients
      with recurrent aphthous ulcers (RAU) or Behcet's disease (BD). For this purpose,
      formalin-fixed biopsy specimens were obtained from 13 pre-ulcerative oral
      aphthous lesions of nine RAU and four BD patients. Five specimens of normal oral
      mucosa (NOM) from five normal control subjects and 10 specimens of oral erosive
      or ulcerative lesions from 10 patients with erosive lichen planus (ELP) were also
      included. EBV-DNA was detected by PCR in 5 of the 13 (38.5%) pre-ulcerative oral
      aphthous lesions, two from RAU patients and three from BD patients. However, no
      EBV-DNA was demonstrated in five NOM specimens from normal control subjects and
      in 10 specimens of oral lesions from ELP patients. EBV-DNA was also demonstrated
      in patients' peripheral blood lymphocytes and/or plasma, suggesting that the
      lymphocytes may be the reservoir of latent EBV infection and there is EBV
      shedding in the plasma. EBV-DNA was detected by ISH in only one PCR-positive
      case; the reaction product was found to deposit on the nuclei of some of the
      epithelial cells and lymphocytes. By immunohistochemistry, expression of Epstein
      Barr nuclear antigen and EBV/C3d receptors was also noted in some of the
      epithelial cells and lymphocytes in this ISH-positive case. Therefore, we suggest
      that the epithelial cells of pre-ulcerative oral aphthous lesions may be infected
      by EBV through EBV-infected lymphocytes; also, the cytotoxic T lymphocyte-induced
      lysis of the EBV-infected epithelial cells, but not the virus-induced cytolysis,
      may be the main mechanism causing oral ulcer formation. Our data provide
      preliminary evidence for an association of EBV with pre-ulcerative oral aphthous
      lesions in RAU and BD patients.

PMID- 9563573
TI  - Oral manifestations of HIV infection in 600 South African patients.
AB  - Oral lesions associated with HIV infection, as classified by the EC-Clearinghouse
      on Oral Problems related to HIV infection and the WHO Collaborating Centre on
      Oral manifestations of the immunodeficiency virus, were studied in 600
      consecutive HIV-infected patients in Cape Town, South Africa. One or more lesions
      were seen in 60.4% of cases. Combined candidal lesions were evident in 37.8%,
      hairy leukoplakia in 19.7% and combined gingival/periodontal lesions in 8.5% of
      patients seen. Lesions less commonly recorded include oral ulceration (2.9%) and
      Kaposi's sarcoma (1.5%). The clinical range of lesions seen is similar to those
      reported elsewhere, but socio-cultural differences allowed no reliable
      comparison. More than a quarter of our patients had oral soft tissue discomfort
      necessitating treatment; in 3.3% these were the presenting symptom. This
      indicates a potential major public health concern requiring education in
      recognition and appropriate referral and management.

PMID- 9563574
TI  - Spindle cell carcinoma of the gingiva: report of an autopsy case.
AB  - An autopsied case of an 80-year-old man with spindle cell carcinoma of the
      gingiva is reported. The tumor was polypoid and mostly composed of a sarcomatous
      proliferation of spindle cells with a small focus of squamous cell carcinoma at
      the stalk portion. The carcinoma metastasized to a cervical lymph node, lungs and
      pleura with extension to the diaphragm. In the metastatic lymph node, the
      squamous cell component was more prominent than the spindle cell one, while only
      anaplastic pleomorphic carcinoma cells were found in the lungs. The spindle or
      anaplastic cells were immunohistochemically positive for vimentin and
      carcinoembryonic antigen (CEA) but not for other epithelial antigens. We have
      concluded that the sarcomatoid component arose from the oral squamous cell
      carcinoma by a metaplastic process. This is the first case report of an oral
      spindle cell carcinoma examined by autopsy.

PMID- 9563576
TI  - The role of clinical neurophysiology in the management of epilepsy.
AB  - Clinical neurophysiologic studies have an important role in the diagnosis and
      management of the patient with epilepsy. Epilepsy is a clinical diagnosis and the
      EEG is an important adjunct used to differentiate epileptic seizures from
      nonepileptic events, refine the diagnosis of epilepsy into specific seizure types
      and epileptic syndromes, and provide a measure of brain function. The value of
      the EEG is highly dependent on the clinical context in which it is being applied.
      In some epilepsies the interictal EEG may be diagnostic whereas in others an
      ictal recording may be necessary to obtain a specific diagnosis. Both the
      interictal and ictal EEG characteristics vary with specific seizure types and
      epilepsies and are described in detail in this review. The usefulness of the EEG
      in the management of epilepsy and in aiding in the decision to discontinue
      antiepileptic therapy is also discussed.

PMID- 9563575
TI  - Odontogenic ghost cell carcinoma: a case report with immunohistochemical and
      ultrastructural characterization.
AB  - The odontogenic ghost cell tumor (OGCT) is the rare, neoplastic variant of the
      calcifying odontogenic cyst (COC). To date, there have been only four reports of
      malignant OGCTs, in five patients. We report an additional case of a malignant
      odontogenic ghost cell tumor that involved the right maxilla of a 20-year-old
      man. Our report includes its immunocytochemical and ultrastructural
      characterization.

PMID- 9563577
TI  - Evoked potentials in clinical trials for multiple sclerosis.
AB  - Multiple sclerosis produces disruption of conduction in the central nervous
      system by a variety of mechanisms, relating, in part, to loss of the myelin
      sheath. Although often not well correlated with the clinical course of the
      disease in individual patients, the resulting evoked potential (EP) disturbances
      can serve as measures of an accumulating disease burden, particularly in
      longitudinal population studies. Accordingly, EPs can serve as useful instruments
      for assessing the effectiveness of therapeutic agents which may alter the course
      of the multiple sclerosis. Furthermore, since EPs measure conduction within the
      central nervous system, they provide a means of directly assessing symptomatic
      treatments designed to improve central conduction.

PMID- 9563578
TI  - Electrodiagnostic studies in clinical trials for motor neuron disease.
AB  - Motor neuron disease (MND) is a group of neurodegenerative disorders
      characterized by death of upper motor neurons (UMN) and lower motor neurons
      (LMN). Clinical study of UMN loss is limited, but electrodiagnostic studies can
      be used readily to assess the functional state of LMN. Electrodiagnostic studies
      are regularly used in making the diagnosis of amyotrophic lateral sclerosis (ALS)
      and other forms of MND. They can also be used to follow disease progression and
      serve as end point measures in drug trials. In this role, electrodiagnostic
      studies can provide specific information not readily available from measurement
      of muscle strength or clinical functional scales. This article emphasizes the
      primary pathologic and secondary physiologic changes that take place after LMN
      loss and how they can be assessed by electrodiagnostic studies. It reviews the
      uses of routine electrodiagnostic studies for the diagnosis of MND but focuses on
      how special electrodiagnostic studies can be used as end point measures in drug
      trials.

PMID- 9563579
TI  - Clinical trials for polyneuropathy: the role of nerve conduction studies,
      quantitative sensory testing, and autonomic function testing.
AB  - Clinical trials to assess the treatment of diabetic and other forms of
      polyneuropathy are becoming increasingly common. Nerve conduction studies,
      quantitative sensory testing, and autonomic function testing are often used in
      these trials. This article reviews the sensitivity and reproducibility of these
      measures to detect change in peripheral nerve function during long-term trials.
      The attributes of nerve conduction studies that are likely to be most useful are
      summated or averaged sensory nerve action potential amplitudes and averaged motor
      nerve conduction velocities. Summated or averaged compound muscle action
      potential amplitude and mean F-wave latencies are also highly informative.
      Vibratory detection thresholds are sensitive, specific, and highly reproducible
      for assessment of large myelinated sensory fibers, with cooling and warming
      detection thresholds also having good sensitivity for small myelinated sensory
      fibers. Although less well validated for longitudinal trials, visual analogue
      scale scoring of heat pain provides assessment of unmyelinated sensory fibers.
      Heart rate variation to deep breathing, Valsalva, or standing are useful to
      assess cardiac autonomic function. Based on these data that are reviewed and
      consistent with the conclusions of previous consensus conferences, a combination
      of these studies is recommended.

PMID- 9563580
TI  - Is spectral analysis of the surface electromyographic signal a clinically useful
      tool for evaluation of skeletal muscle fatigue?
AB  - Normal values for initial median frequency (IMF) of the electromyographic (EMG)
      power-density spectrum must be determined before EMG spectral analysis can be
      used to evaluate clinically muscle fatigue. This study attempts to establish
      normal values in four muscles. Thirty-one healthy subjects performed isometric
      contractions of the biceps brachii, triceps, deltoid, and tibialis anterior
      muscles at 50% maximum voluntary contraction. Linear regression analysis was used
      to compute the IMF and the slope of the median frequency as it decayed with
      fatigue over 45 seconds. The IMF of the tibialis anterior (mean +/- standard
      deviation, 116 +/- 20 Hz) was significantly higher (p < 0.001) than that of the
      biceps (90 +/- 18 Hz), triceps (85 +/- 18 Hz), and deltoid (87 +/- 15 Hz). The
      deltoid and tibialis anterior had the steepest slopes. The IMF of all muscles was
      greater in men than in women, but gender did not affect the slope. This study
      attempted to establish normal values for IMF and slope in specific muscles.
      However, the range of normal values is so broad that it may preclude the clinical
      use of spectral analysis to evaluate muscle fatigue.

PMID- 9563581
TI  - Unilateral alpha reactivity: an electroencephalographic finding in albinism.
AB  - Persons with various forms of albinism frequently have misrouting of their optic
      nerve fibers. Visual evoked potential (VEP) studies can confirm this because
      monocular stimulation tends to result in asymmetrical rather than symmetrical
      occipital response. This type of decussation abnormality is associated only with
      albinism. In the electroencephalogram (EEG) of normal subjects, unilateral eye
      opening or closing does not affect the frequency, reactivity, regulation, and
      symmetry of alpha rhythm. In contrast, in our study, 6 of 19 persons with
      oculocutaneous and ocular albinism responded to unilateral eye opening with
      contralateral disappearance or significant attenuation of their alpha rhythm. The
      most likely explanation of this phenomenon is that the visual pathway misrouting
      is complete or nearly complete in some children with albinism so that one rather
      than both occipital lobes receive visual information from each eye. This type of
      alpha behavior, like VEP studies, supports the diagnosis of albinism, and such
      testing can be easily performed during a routine EEG recording.

PMID- 9563582
TI  - Simple and novel method for measuring conduction velocity of A delta fibers in
      humans.
AB  - We report a simple new method for measuring the conduction velocity (CV) of A
      delta fibers in normal subjects. A large positive component of somatosensory
      evoked potential (SEP) whose peak latency was approximately 250 ms was clearly
      recorded only when strong electrical stimulation causing a definite painful
      feeling was applied to the skin. The CV of the peripheral nerve was calculated by
      measuring the latency difference of this component between the distal-stimulated
      SEP and proximal-stimulated SEP and the distance between two stimulus sites. The
      CV was approximately 11.4 m/s, (range 8.8-15.9 m/s), in the range of A delta
      fibers. The sleep effect on pain-related SEP was also observed in 3 subjects. The
      amplitude of pain-related SEP decreased with the progress of sleep stage. This
      simple and novel method is available in most clinics and should be very useful in
      investigating the physiologic functions of peripheral nerves in patients as well
      as normal subjects.

PMID- 9563583
TI  - Contribution of initial median-nerve somatosensory evoked potentials and
      brainstem auditory evoked potentials to prediction of clinical outcome in
      cerebrovascular critical care patients: a statistical evaluation.
AB  - In a prospective study of 200 patients with cerebrovascular disease (48
      intracerebral hemorrhages, [ICH]; 64 subarachnoid hemorrhages, [SAH]; 48
      supratentorial and 40 infratentorial ischemic strokes), we assessed the
      individual and combined prognostic value of median-nerve somatosensory evoked
      potentials (SEP) and brainstem auditory evoked potentials (BAEP) within 72 hours
      of admission. Clinical outcome was graded in three ranked categories according to
      a modified Glasgow Outcome Scale. Likewise, the initial SEP and BAEP findings
      were graded in a three-class score. In all groups, the SEP were significantly
      correlated with outcome (P < 0.01). Likewise, after partialling out the
      prognostic effect of SEP, the contingency between BAEP and outcome was
      statistically significant, except in ICH (P = 0.07). The contingencies of SEP and
      outcome in ICH and supratentorial infarcts were higher than the corresponding
      partial contingencies for BAEP, while the latter were higher in infratentorial
      infarction and SAH. Therefore, in all disease groups except for SAH, the multiple
      contingency coefficients ranging from 0.67 to 0.75 were statistically significant
      and greater than either simple or partial contingencies alone. The results of the
      two evoked potential modalities combined permit statistically significant
      superior prognostication in most cerebrovascular diseases when compared to those
      of either of the modalities alone.

PMID- 9563584
TI  - Analysis of polysomnographic events surrounding 252 slow-wave sleep arousals in
      thirty-eight adults with injurious sleepwalking and sleep terrors.
AB  - A systematic study of electrophysiologic events [eight-channel EEG,
      electrocardiogram, electromyogram (EMGs)] surrounding 252 arousals from slow-wave
      sleep (SWS) in adults with sleepwalking (SW) and sleep terrors (ST) is reported.
      Hospital-based, overnight polysomnographic monitoring was conducted in 38 adults
      presenting to a sleep disorders center with injurious SW, ST (21 males, 17
      females; mean age 29 years, range 17-69 years). Before nonbehavioral or
      behavioral arousals from SWS, neither EEG "delta wave buildup," nor heart rate
      (HR) acceleration, nor tonic/phasic EMG activation was identified. The
      postarousal EEG demonstrated three patterns: (a) diffuse, rhythmic, delta
      activity with a typical frequency of 2.2 Hz, a typical amplitude of 85 microV,
      and a typical duration of 20 s; (b) diffuse delta and theta activity intermixed
      with alpha and beta activity; and (c) prominent alpha and beta activity.
      Multichannel, high-voltage, delta activity was observed in <2% of all prearousal
      periods. HR acceleration emerged abruptly with SWS arousals, with significant
      changes in mean pre- versus postarousal HR (p < .001). Macrostructural sleep
      parameters ("sleep architecture") were intact. Therefore, our findings in adults
      with SW, ST strongly support the classification of SW/ST as disorders of (abrupt)
      arousal.

PMID- 9563585
TI  - High-frequency components in the alpha band and memory performance.
AB  - We tested the hypothesis that alpha band power is correlated with memory
      performance. For a sample of 68 subjects, the ongoing electroencephalogram (EEG)
      was analyzed during three experimental conditions: eyes closed (EC), eyes open
      (EO), and memorizing words. The results show that the upper alpha band of
      approximately 10-12 Hz is related to memory performance. Only within this
      frequency range did we obtain significant positive correlations between memory
      performance and EEG power. A comparison of power spectra showed that within the
      range of the upper alpha band good performers had significantly greater
      normalized percent power than bad memory performers. In contrast to condition EC,
      the obtained relationship between upper alpha power and memory performance was
      particularly strong during EO and memorizing words.

PMID- 9563587
TI  - The last word.

PMID- 9563586
TI  - Improvement of P300 latency by treatment of vitamin B12 deficiency.

PMID- 9563588
TI  - Interdisciplinary microvascular reconstruction of maxillary, midfacial and skull
      base defects.
AB  - Microvascular reconstruction techniques are increasingly used for reconstructive
      purposes in the maxilla, the midface and the cranial base. In the maxillary area,
      they provide the possibility of a safe closure of nasoantral perforations which
      are too large for local coverage with or without additional bony reconstruction
      (n = 14). A basis for prosthodontic rehabilitation with implant-borne dentures is
      also provided. Additional free bone grafts are often a prerequisite for implant
      insertion. In reconstruction of the midface, microvascular techniques can
      separate functional units, provide tissue augmentation and give orbital support
      (n = 12). In skull base and cranial defects, a safe coverage of duraplasties and
      scalp reconstructions is achieved (n = 9).

PMID- 9563590
TI  - Secondary correction of bilateral cleft lip deformity with simultaneous Abbe flap
      and nasal repair.
AB  - For secondary repair of a bilateral cleft lip deformity with a short columella
      and defective upper lip, simultaneous correction of the lip and nose is ideal. We
      perform a nasal repair through a bilateral reverse-U incision and columella
      elongation using the upper lip. An Abbe flap is then transferred to the upper lip
      defect. This procedure enables total reconstruction of characteristic bilateral
      cleft lip deformities in one stage. We have applied this method to 15 patients (9
      males and 6 females) with an average age of 18.7 years. Although some patients
      need jaw surgery, all have been satisfied with the results.

PMID- 9563589
TI  - Indications and limitations of three-dimensional models in cranio-maxillofacial
      surgery.
AB  - Anatomical, life-like, three-dimensional (3D) models have a definite place in
      cranio-maxillofacial surgery. Our experience with 541 computer tomography (CT)
      based 3D models employed in aiding corrective surgery of tumours, dysgnathia,
      traumatology, alveolar atrophy, congenital malformation and asymmetrical
      malformations in our department is discussed. From July 1988 to February 1997, 3D
      models of 346 patients were used. Most of these were produced at our clinic. The
      indications, advantages and limitations of 3D-models were analysed
      retrospectively. In the case of congenital malformations (n = 60), models
      facilitated precise diagnosis of the skeletal deformity. Simulation surgery
      allowed prediction and solution of intraoperative problems prior to the actual
      patient operation. Size, shape and localization of defects caused by trauma (n =
      64), osteoradionecrosis (n = 17) or osteomyelitis (n = 2) determined the choice
      of transplant donor site. In patients suffering from dysgnathia (n = 144), 3D
      models enabled exact positioning of the jaws. Precise planning could only be
      accomplished with the help of 3D models, especially for asymmetrical
      malformations (n = 12). In cases of severe atrophy of the alveolar crest (n =
      45), exact measurement of the bone was possible and facilitated the decision as
      to whether dental implants, bone transplants or a combination of these were
      indicated. The positioning of transplants and implants was carried out in the
      ideal relation to the opposite jaw. In tumour patients (n = 186), it is not
      always possible to identify the tumour borders precisely on the CT scan or 3D
      model. Therefore, the defect was assumed to be bigger, a longer bridging plate
      constructed and this measurement corrected according to the intraoperative
      situation. The advantage of the 3D models consisted of an accurate representation
      of anatomical structures, bone or soft tissue. This allows precise preoperative
      diagnosis, operation planning and model operations. Due to this, the correct
      approach as well as operation technique could be chosen, outcomes of constant
      high quality were achieved, and there was a reduction in operation time.

PMID- 9563591
TI  - Reproducibility of aimed-at profiles.
AB  - Would a surgeon always draw the same aimed-at profile when planning the
      correction of a face with evidently malpositioned jaws? The same 10 profile lines
      were given to seven maxillofacial surgeons on two occasions at intervals of 6
      months. The differences in absolute and proportional vertical measurements were
      compared. It is shown that the variations between first and second drawing were
      quite large for individual values. However, even the mean differences per
      measurement vary between surgeons from 0 to 10%. The drawings for the whole group
      corresponded reasonably well with the ratios given by Farkas and Munro (1987) but
      were rather divergent from the 'golden dimensions' proposed by Brons and Mulie
      (1993). Considering the sometimes significant differences, one is advised not to
      draw profiles 'off the cuff' but to use a construction system for planning
      osteotomies.

PMID- 9563592
TI  - Orthognathic surgery: patients' subjective findings with focus on the
      temporomandibular joint.
AB  - Two hundred and ninety-six patients who underwent various orthognathic surgery
      procedures were questioned, a minimum of 1 year postoperatively, on their overall
      subjective findings. Patient satisfaction, willingness to resubmit to surgery,
      self-confidence and subjective changes in their temporomandibular joints (TMJ)
      function and masticatory efficiency were evaluated. 87% would undergo the
      combined surgical-orthodontic treatment again. Self-confidence improved in 77% of
      the patients. There was a subjective improvement in TMJ function in 40% of the
      patients and a worsening in 11%; masticatory function was improved in 41% and
      worsened in 7% of the patients.

PMID- 9563593
TI  - Relationship between condylar position, dentofacial deformity and
      temporomandibular joint dysfunction: an MRI and CT prospective study.
AB  - The possible relationship between the morphometric characteristics (condylar and
      temporomandibular joint (TMJ) disc position) of the TMJ and the TMJ clinical
      findings (normal versus TMJ disorders) in different types of dentofacial
      deformities was studied. Forty-eight patients with dentofacial deformities (96
      TMJs) were investigated preoperatively and 10 patients (20 TMJs) without
      deformities were studied as a control group, clinically and radiographically,
      using computer tomography (CT) and magnetic resonance imaging (MRI), to assess
      the position of the mandibular condyle and the TMJ disc in the sagittal, coronal
      and horizontal planes. Fifteen of the 28 joints (53.6%) of patients diagnosed as
      class II dentofacial deformity had internal derangements and anteriorly displaced
      discs. The incidence of internal derangement in the class I and class III groups
      was lower (10%). An increased horizontal angle of the mandibular condyle and a
      posteriorly seated condyle were found in patients diagnosed as class II
      dentofacial deformity when compared with the control group. The rest of the
      patients studied showed no significant differences. The same results were
      encountered when the patients with moderate to severe TMJ pathology were studied,
      both clinically (using the Helkimo index modified by Athanasiou) and by MRI.

PMID- 9563594
TI  - Mandibular distraction osteogenesis: a comparison of distraction rates in the
      rabbit model.
AB  - The rabbit model has been used to study the effects of different rates of
      distraction upon mandibular bone. Bilateral distraction was performed at two
      different rates anterior to the molar teeth. Both experimental groups were
      significantly inferior to sham operated controls in terms of bone density (DEXA)
      and mechanical testing. No difference in new bone formation between the two
      distraction rates was detected by these modalities. However, histological
      examination revealed non-union to be more common in the rapidly distracted group.
      This suggests that attempts to shorten the duration of external fixation in
      clinical mandibular distraction osteogenesis should be by methods other than more
      rapid distraction.

PMID- 9563595
TI  - Influence of different pilot hole sizes on torque measurements and pullout
      analysis of osteosynthesis screws.
AB  - When screws are inserted in thick cortical bone, a small pilot hole size,
      corresponding to the core diameter of the screw, can result in high torsional
      stress, leading to screw fracture. The aim of this study was to enlarge the drill
      size up to a critical pilot hole size (CPHS) which, if exceeded, means a rapid
      decrease in the screw holding power. 1.5 and 2 mm titanium screws were inserted
      in discs of polyvinylchloride (PVC), wood and porcine mandibular bone with
      thicknesses differing between 2 to 4 mm, using an increasing pilot hole size
      between 66% and 95% of the screw external diameter. Torque measurements and
      pullout tests were performed and the CPHS was calculated. In torque measurements,
      the CPHS of microscrews ranged between 83% and 85% of the screw external diameter
      (SED). The CPHS of miniscrews lay between 80% and 90% of SED. In pullout
      analysis, the CPHS of microscrews ranged between 83% and 89% of SED; the CPHS of
      miniscrews lay between 79% and 91% of SED. The mean of the CPHS was calculated to
      be approximately 85% of the SED. Up to this critical point, the pilot hole size
      may be increased without affecting the holding power of the screws.

PMID- 9563596
TI  - Aneurysmal bone cysts of the jaws: clinicopathological features, radiographic
      evaluation and treatment analysis of 17 cases.
AB  - This article re-evaluates the various clinicopathological presentations and array
      of radiographic features displayed by aneurysmal bone cysts (ABCs) of the jaws.
      In this retrospective clinical study, 17 cases of ABCs of the jaws surgically
      treated during an 11-year period from 1986-1997 are evaluated. The age and sex
      distribution, diagnostic characteristics, mode of treatment and long-term
      surgical results are presented and compared with the international literature.
      Investigation included serial clinical examinations, appropriate radiographic
      evaluation, CT scans and angiograms when indicated. All the patients had
      mandibular lesions and were managed by complete surgical curettage of the
      lesions. Ten were in males (58.8%) and seven (41.2%) in females. The mean age of
      occurrence was 21.05 years, ranging from 7 to 58 years. Clinical presentation in
      these patients ranged from an asymptomatic incidental radiographic finding to an
      expanding, rapidly progressive and destructive lesion resulting in a pathological
      fracture. Radiographic findings varied from unicystic radiolucencies or moth
      eaten radiolucencies to extensive multilocular lesions causing bilateral
      expansion and destruction of the mandibular cortices. Twelve of the patients
      (70.5%) could recall a history of trauma. Needle aspiration with a 16 or 18 guage
      needle was positive, producing syringes full of blood in all but two of the cases
      (88.2%). Six cases (35.2%) were extremely vascular and had increased rapidly in
      size, and three required angiographic studies for preoperative diagnosis and
      differentiation from other vascular entities. Nine of the cases (52.9%) were
      found in the mandibular angle-ramus area. Four cases (23.5%) required extraoral
      surgical access for curettage while the remainder were treated intraorally.
      During the follow-up period, which ranged from 2-11 years, no recurrences have
      occurred. Restoration of facial symmetry and bone formation has been favourable
      in all patients, despite the fact that grafts were not used. This 11-year study
      shows that ABCs present with varied clinicopathological and radiographic features
      and thus may pose a diagnostic dilemma. As we have not noted any recurrences
      following surgical curettage of mandibular lesions, we feel that initial surgical
      resection or bone grafting is not necessary, provided that adequate access and
      complete curettage can be obtained.

PMID- 9563597
TI  - Actinomycotic osteomyelitis of the mandible: review of 15 cases.
AB  - The authors have analysed 15 cases of actinomycotic osteomyelitis of the
      mandible. Primary actinomycotic inflammation of the mandible was diagnosed in
      nine patients, secondary in six patients (following fracture or resection of the
      mandible). The diagnosis was established on the basis of the clinical examination
      confirmed by bacteriological and/or histopathological tests. The basic method of
      treatment was antibiotic therapy of long duration. Surgical treatment was
      performed in all patients. Twelve of fifteen patients who had received the
      therapy and proved asymptomatic for 1 year to 23 years were recognized to be
      cured of the disease. In three patients, a single recurrence of the disease was
      observed after 1.5-2 months.

PMID- 9563598
TI  - Computer-aided navigation in secondary reconstruction of post-traumatic
      deformities of the zygoma.

PMID- 9563599
TI  - Relationship of xenogeneic microchimerism to graft outcome in hamster-to-rat lung
      xenotransplantation.
AB  - BACKGROUND: In spite of the progress in allogeneic microchimerism research, few
      reports have dealt with the biologic relevance of xenogeneic microchimerism after
      organ xenotransplantation. These experiments were designed to analyze the
      development of xenogeneic microchimerism and its relationship to graft outcome in
      hamster-to-rat lung xenotransplantation. METHODS: Golden Syrian hamsters were the
      donors and Lewis rats the recipients of xenogeneic lung transplantation. Animals
      were divided into three groups: group 1 were untreated; group 2 received
      cyclophosphamide (10 mg/kg/day for 6 days) and a short course of FK506 (2
      mg/kg/day for 8 days); and group 3 were treated with cyclophosphamide and a long
      course of FK506 (2 mg/kg/day for 8 days, 1 mg/kg/day for 23 days, and then 0.5
      mg/kg/day continuously). Xenogeneic microchimerisms were evaluated by use of
      polymerase chain reaction with primers specific for the hamster hypoxanthine
      phosphoribosyl-transferase gene. RESULTS: The median graft survival times for
      groups 1, 2, and 3 were 3 days (n = 6), 22 days (n = 7), and 96.5 days (n = 6),
      respectively. In groups 1 and 2, the incidence of microchimerisms declined in
      parallel with the progression of rejection. In group 3, it changed dynamically,
      initially declining, then progressively increasing and finally disappearing.
      CONCLUSIONS: In the short-term graft survivors, xenogeneic microchimerism in the
      peripheral blood was closely related to graft outcome. However, it showed dynamic
      changes and finally disappeared in long-term graft survivors, and the incidence
      of microchimerism at a single time point did not reflect the donor-recipient
      immunologic status.

PMID- 9563600
TI  - Increased expression of HDJ-2 (heat shock protein 40) and heat shock protein 70
      in biopsy specimens of transplanted human lungs.
AB  - BACKGROUND: Heat shock proteins are expressed during several forms of stress and
      inflammation. This study was done to determine whether the expression of heat
      shock protein HDJ-2 (heat shock protein 40), heat shock protein 60, and heat
      shock protein 70 are increased during rejection in human pulmonary allografts.
      METHODS: Thirty-five transbronchial biopsy specimens were obtained from adult
      lung transplant recipients. Histologic analysis and assessment of heat shock
      protein HDJ-2, heat shock protein 60, and heat shock protein 70 mRNA expression
      was performed. Total RNA was extracted, reverse transcribed, and amplified by
      polymerase chain reaction with oligonucleotide primers specific for the heat
      shock proteins. The identity of the amplified message was verified by Southern
      blot and slot blot analysis. RESULTS: The expression of heat shock protein HDJ-2
      was significantly higher in samples from lung transplant recipients undergoing
      rejection when compared with recipients without rejection or infection. Heat
      shock protein 70 expression was also increased in rejection. Expression of heat
      shock protein 60 did not show any increase in recipients with no evidence of
      rejection and infection or transplant recipients with rejection or infection.
      Serial analysis of heat shock protein HDJ-2 and heat shock protein 70 obtained in
      biopsy specimens during and after rejection showed a decrease of heat shock
      protein HDJ-2 and heat shock protein 70 expression after resolution of lung
      rejection. CONCLUSION: Our data demonstrate that the expression of heat shock
      protein HDJ-2 and heat shock protein 70 increases during lung rejection. However,
      only heat shock protein HDJ-2 was able to differentiate between rejection and
      infection. Measurement of heat shock protein HDJ-2 in transbronchial biopsy
      specimens may assist in the differential diagnosis between rejection and
      infection in lung transplant recipients.

PMID- 9563601
TI  - Use of leukocyte depletion to decrease injury after lung preservation and
      rewarming ischemia: an experimental model.
AB  - BACKGROUND: Hypothermia is critical for proper lung preservation. Ideally, the
      lungs should be maintained at the optimal preservation temperature during the
      entire ischemic interval. Lung rewarming during implantation is commonly
      observed. This study was undertaken to investigate the severity of rewarming
      ischemia on preservation injury and the possibility of minimizing this by use of
      leukocyte depletion during initial reperfusion. METHODS: Four experimental groups
      were tested as follows: neonatal piglet heart-lung blocks were either (1) placed
      on an isolated, blood-perfused, working heart-lung circuit without intervening
      ischemia (control, n = 6), (2) reperfused on the circuit with whole blood (WB, n
      = 6) after 13 hours of preservation, (3) reperfused with WB after 12 hours of
      preservation and 1 hour of rewarming (RWB, n = 5), or (4) reperfused with
      leukocyte-depleted blood for an initial 10 minutes followed by WB, after 12 hours
      of preservation and 1 hour of rewarming (n = 6). All groups were studied for 4
      hours. RESULTS: The partial pressure of arterial oxygen and lung compliance were
      significantly lower in the RWB group than in controls (113.8+/-33.1 vs 417.3+/
      6.2 mm Hg, p < 0.01; and 0.8+/-0.2 vs 2.9+/-0.4 ml/cm H2O, p < 0.05,
      respectively). Pulmonary vascular resistance and lung wet/dry weight ratios were
      significantly higher in the RWB group than in controls (15884.1+/-11354.8 vs
      6108.3+/-1309.9 dyne x sec x cm[-5], p < 0.05; and 7.13+/-0.24 vs 5.82+/-0.35, p
      < 0.05, respectively). The WB and leukocyte-depleted groups did not differ
      significantly from controls for any measured parameter. CONCLUSIONS: This model
      confirms that rewarming ischemia during lung implantation exacerbates reperfusion
      injury. Leukocyte-depleted reperfusion as tested for a short period of time (10
      minutes) ameliorates this injury and therefore should be considered for clinical
      lung transplantation.

PMID- 9563602
TI  - Assessment of the progression of cardiac allograft vasculopathy by dobutamine
      stress echocardiography.
AB  - BACKGROUND: After heart transplantation, accelerated coronary vasculopathy is a
      major factor that limits long-term survival and is usually detected by serial
      coronary angiography. The aim of this study was to determine whether dobutamine
      stress echocardiography could accurately identify the progression of cardiac
      allograft vasculopathy. METHODS: Two sequential controls by dobutamine stress
      echocardiography were performed at an 18-month interval in 37 heart transplant
      recipients at the time of their routine coronary angiography. The first control
      (control 1) occurred 37+/-20 months after transplantation, and the second control
      (control 2) occurred after 56+/-21 months. Standard echocardiographic views were
      acquired at baseline and at incremental dobutamine infusion levels. Regional wall
      motion score was calculated in a 16-segment model, and each segment was graded
      from 1 (normal) to 4 (dyskinesia). Visual and quantitative coronary angiographic
      analysis were used to assess the severity of the coronary vasculopathy. RESULTS:
      The incidence of coronary vasculopathy increased from 46% (17/37 patients, four
      of whom had stenoses > 50%) at control 1 fo 70% (26/37 patients, six of whom had
      stenoses > 50%) at control 2. Progression of coronary vasculopathy was diagnosed
      by coronary angiography in 25 patients (new abnormalities in 19 and worsening of
      previous abnormalities in 6). Dobutamine stress echocardiography correctly
      identified the progression of vasculopathy in 21 of these 25 patients (84%) with
      new abnormalities in 17 and worsening in four. In the four remaining patients
      with evidence of progression of vasculopathy on coronary angiography, the result
      of dobutamine stress echocardiography was abnormal in three patients and normal
      in only one. Therefore dobutamine stress echocardiography results were abnormal
      in 12 patients at control 1 (sensitivity: 65%, specificity: 95%) and in 27 at
      control 2 (92% sensitivity, 73% specificity). CONCLUSION: Dobutamine stress
      echocardiography is a sensitive, noninvasive method to diagnose the progression
      of allograft vasculopathy, and a negative test result is a strong predictor of
      absence of allograft coronary vasculopathy. Therefore serial routine coronary
      angiography may be deferred when dobutamine stress echocardiography results are
      normal.

PMID- 9563603
TI  - Pretransplantation risk factors for death after heart transplantation: the Henri
      Mondor experience.
AB  - BACKGROUND AND METHODS: Risk factors for death after primary heart
      transplantation were identified by analyzing our total experience with 234
      patients who underwent transplantation at our institution from May 28, 1979, to
      May 27, 1996. RESULTS: There were 205 male and 29 female patients. Mean recipient
      age was 48.5+/-10.9 years (standard deviation). Recipient diagnosis included
      ischemic cardiomyopathy in 103 (44%), idiopathic cardiomyopathy in 98 (42%),
      valvular heart disease in 17 (7%), congenital heart disease in 4 (2%), and other
      diagnoses in 12 (5%) patients. Donor age was 32+/-10.2 years. Graft ischemic time
      was 138.1+/-51.8 minutes. The operative mortality rate was 23.5%. Actuarial
      survival estimates for all patients at 1, 5, and 10 years were 62%, 50%, and 44%,
      respectively. The three most common causes of death (both early and late) after
      primary heart transplantation were infection (27.4%), acute rejection (18.9%),
      and early graft failure (17.9%). Multivariate logistic regression analysis
      identified older recipient age (p = 0.007), higher preoperative pulmonary
      vascular resistance (p = 0.01), recipient preoperative hepatic insufficiency (p =
      0.001), and gender mismatch (p = 0.02) as independent predictors of early death
      (within 3 months of the procedure). Multivariate proportional hazard regression
      analysis revealed that recipient idiopathic cardiomyopathy (p = 0.02) and
      recipient preoperative liver failure (p = 0.01) were independent risk factors for
      late death (after 3 months). CONCLUSION: These results underscore the importance
      of adequate recipient selection and recipient/donor matching for short- and long
      term survival after primary heart transplantation.

PMID- 9563604
TI  - Left ventricular end-diastolic volume index, age, and maximum heart rate at peak
      exercise predict survival in patients referred for heart transplantation.
AB  - BACKGROUND: This study sought to define clinical predictors of survival in
      patients under consideration for heart transplantation and demonstrate possible
      improvements in the prediction of outcome when considering the identified
      predictors in addition to peak oxygen consumption. Peak oxygen consumption is
      currently the most important criterion for determining the timing and
      appropriateness of heart transplantation in ambulatory patients. METHODS: To
      identify other possible predictors of survival in patients with heart failure, we
      reviewed clinical, exercise, and radionuclide ventriculographic data on 112
      patients referred for heart transplantation evaluation. Predictors of 1-year (n =
      86) and overall (n = 112) survival to the combined end point of freedom from
      death or pretransplantation admission for inotropic or mechanical support were
      identified in multivariate analysis. RESULTS: The mean age was 51+/-9 years, and
      the mean duration of follow-up was 408+/-366 days. The mean left ventricular
      ejection fraction was 0.22+/-0.07, and the mean peak oxygen consumption was
      12.3+/-3.7 ml/min/kg. Age (odds ratio 1.087, 95% confidence interval [CI] 1.021
      to 1.157), percentage of the maximum predicted heart rate at peak exercise (odds
      ratio 0.958, 95% CI 0.924 to 0.992), and left ventricular end-diastolic volume
      index (odds ratio 1.019, 95% CI 1.006 to 1.033) were independent predictors of
      the 1-year combined end point. CONCLUSION: Age, heart rate at peak exercise, and
      left ventricular end-diastolic volume index are independent predictors of
      prognosis in patients with advanced heart failure and may provide additional
      prognostic information for the risk-stratification of potential heart transplant
      recipients.

PMID- 9563605
TI  - Detection of herpesvirus-like sequences in Kaposi's sarcoma from heart transplant
      recipients.
AB  - BACKGROUND: Herpesvirus-like DNA sequences have been found in lesions from
      patients with Kaposi's sarcoma in its several forms, suggesting that this tumor
      may be caused by a new herpesvirus, referred to as Kaposi's sarcoma-associated
      herpesvirus or human herpesvirus 8. METHODS: We analyzed DNA from skin and lung
      lesions, healthy skin, and peripheral blood mononuclear cells of three heart
      transplant recipients with Kaposi's sarcoma. We also studied DNA from normal skin
      and from peripheral blood of Kaposi's sarcoma-free heart transplant recipients.
      Samples were analyzed by polymerase chain reaction with specific primers to
      amplify the KS 330 sequence. RESULTS: The KS 330 fragment was found in Kaposi's
      sarcoma tissue of all three patients, in normal skin of one of them, and in
      peripheral blood of two. It was not detected in any of the samples from skin or
      peripheral blood of heart transplant recipients not affected by Kaposi's sarcoma.
      DNA extracted from a peripheral blood sample of one patient before
      transplantation showed that the KS 330 sequence was already detectable at that
      time. CONCLUSIONS: These findings suggest that Kaposi's sarcoma-associated
      herpesvirus may play a significant role in the pathogenesis of all forms of
      Kaposi's sarcoma. The development of the tumor in transplant recipients may be
      related, at least in some cases, to transplantation-associated immunosuppression,
      rather than to the acquisition of the virus from the donor.

PMID- 9563606
TI  - Soluble interleukin-2-receptor levels as a marker of coronary microvascular
      dysfunction after heart transplantation.
AB  - BACKGROUND: Immunologic mechanisms operating in a milieu of nonimmunologic risk
      factors constitute the principal stimuli that result in progressive cardiac
      allograft vasculopathy. Interleukin-2 has a central role in the development of
      cell-mediated immunity and is a key factor in the induction of a complex network
      of cytokines. On exposure to cytokines, endothelial cells can undergo profound
      alterations of vasomotor function. In this study we characterized the
      relationship between coronary microvascular function and soluble interleukin-2
      receptor (sIL-2R) levels after human heart transplantation. METHODS: We studied
      15 heart transplant recipients after an average follow-up time of 39+/-22 months.
      We measured coronary artery blood flow in an endothelium-dependent manner with
      acetylcholine (50 microg) and in an endothelium-independent manner with
      dipyridamole (0.56 mg/kg) by intracoronary Doppler catheter. Blood samples from
      the superior vena cava were drawn 3 to 12 months after transplantation (early
      value) and at time of the coronary artery flow measurement (present value).
      Coronary artery flow reserve was correlated to sIL-2R levels, which were
      determined by use of an enzyme-linked immunoabsorbent assay. RESULTS: We found a
      significant inverse correlation between impaired endothelium-mediated (p = 0.03)
      but not endothelium-independent relaxation of the coronary microvasculature and
      elevated sIL-2R levels. In heart transplant recipients without acute rejection or
      an infection episode, an sIL-2R-level of more than 800 U/ml was defined as a
      cutpoint, indicating disturbed endothelium-dependent microvascular function.
      Additionally, there was a conspicuous trend toward an inverse correlation between
      early elevated sIL-2R-levels and endothelium-dependent microvascular dysfunction
      (p = 0.06). CONCLUSIONS: The results of this study demonstrate the utility of sIL
      2R, an index of immunologic activity, to be used as a marker and predictor of
      impaired endothelial microvascular function in heart transplant recipients. These
      observations support the hypothesis that after heart transplantation endothelial
      dysfunction in the microcirculation is an immunologic phenomenon.

PMID- 9563607
TI  - Cardiac function and glycogen content after twenty-four-hour preservation with
      various metabolic substrates.
AB  - BACKGROUND: Previous work has suggested that recovery of cardiac function after
      long preservation periods is improved if a suitable exogenous substrate is
      provided. However, interpretation of existing data on the benefit of added
      substrate is complicated by differing preservation media and protocols studied,
      as well as differing models used to evaluate postpreservation recovery. These
      experiments were designed to evaluate glucose, pyruvate, aspartate, and glutamate
      as exogenous substrates for prolonged perfusion preservation of hearts with a rat
      heart model preserved with crystalloid medium and with function quantified in an
      isolated working heart preparation. METHODS: Cardiac function (n = 5/group) and
      tissue glycogen content (n = 5/group) were measured in fresh control rat hearts
      and four groups of hearts preserved for 24 hours in an extracellular-type
      cardioplegic medium containing 11 mmol/L glucose and either 20 mmol/L sodium
      aspartate, 20 mmol/L sodium glutamate, 20 mmol/L sodium pyruvate, or no other
      substrate. Postpreservation cardiac function was measured in an isolated working
      rat heart preparation for a 4-hour reperfusion period. Exogenous substrate
      consumption during preservation and tissue glycogen content at the end of
      preservation were measured with spectrophotometric assays. RESULTS: All hearts in
      the aspartate- and glutamate-preserved groups functioned for the full 4-hour
      period with stroke work that was 50% to 60% of control. Hearts preserved with
      only glucose substrate had inconsistent recovery: two of five hearts in that
      group did not recover, whereas three recovered similar to the aspartate and
      glutamate groups. None of the pyruvate-preserved hearts recovered contractile
      function. There was no association between postpreservation tissue glycogen
      content and extent of cardiac function recovery. CONCLUSION: Aspartate or
      glutamate plus glucose was the best substrate mixture among those tested for long
      term perfusion preservation of hearts. These amino acids offer advantages over
      pyruvate because they produced better recovery of the hearts and because they are
      chemically more stable than pyruvate. Aspartate or glutamate plus glucose also
      produced better postpreservation function compared with glucose alone.

PMID- 9563608
TI  - Prolonged discordant xenograft survival by inhibition of the intrinsic
      coagulation pathway in complement C6-deficient recipients.
AB  - BACKGROUND: Xenotransplantation of vascularized organs between unmodified
      discordant species results in hyperacute graft rejection within minutes to hours
      after graft reperfusion. This process is due to the presence of natural
      xenoreactive antibodies and complement activation, which lead to vessel injury,
      thrombosis, and hemorrhage. Because multiple components of the coagulation and
      complement cascades interact with each other, we have investigated the effects of
      inhibiting these systems together. The recombinant Kunitz type serine protease
      inhibitor (KPI-BG022) tested in these experiments inhibits factor XIIa,
      kallikrein, and plasmin. METHODS: Cardiac xenografts from male Hartley guinea
      pigs were heterotopically grafted into male PVG rats that were either sufficient
      (C6[+]) or deficient (C6[-]) for the complement component C6 and thus formation
      of the membrane attack complex. Experimental animals received KPI 5 mg/kg
      intravenously before reperfusion, and control animals received saline placebo.
      RESULTS: C6(+) recipients rejected their grafts hyperacutely, without a
      significant difference between KPI-treated (0.12+/-0.05 hours) and placebo
      treated (0.13+/-0.06 hours) recipients (n = 10). As expected, C6(-) recipients
      showed prolonged graft survival (17.65+/-3.45 hours, n = 5). However, a single
      intravenous bolus of KPI before releasing the clamps further delayed graft
      rejection in C6(-) recipients (46.2+/-3.3 hours; n = 5). Histologic examination
      at 2, 6, and 12 hours after transplantation showed platelet aggregation and
      inflammatory infiltrates were significantly decreased in KPI-treated (C6[-])
      recipients. However, intragraft hemorrhage was apparent at 6 and 12 hours.
      CONCLUSIONS: We conclude that in vivo inhibition of the intrinsic clotting
      cascade by functional inactivation of factor XIIa has a synergistic effect with
      inhibition of membrane attack complex formation in preventing hyperacute
      discordant xenograft rejection.

PMID- 9563609
TI  - Adjunctive use of inhaled nitric oxide during implantation of a left ventricular
      assist device.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of inhaled nitric
      oxide in the prevention and reversal of pulmonary hypertension during and after
      left ventricular assist device implantation. METHODS: Inhaled nitric oxide (20
      ppm) was administered to seven consecutive patients undergoing implantation of a
      left ventricular assist device at the time of implantation and for the first 24
      hours after operation. RESULTS: Withdrawal of inhaled nitric oxide at 24 hours
      after operation was associated with a significant rise in both the transpulmonary
      gradient (from 8+/-1 to 14+/-2 mm Hg, p < 0.01) and in pulmonary vascular
      resistance (from 110+/-19 to 196+/-32 dynes x sec x cm[-5], p < 0.01). In two
      patients, the rise in pulmonary vascular resistance resulted in a critical fall
      in left ventricular assist device flow and hemodynamic deterioration,
      necessitating urgent reinstitution of inhaled nitric oxide. CONCLUSION: The
      administration of inhaled nitric oxide at the time of left ventricular assist
      device implantation prevents rises in pulmonary vascular resistance that in some
      patients result in critical reductions in left ventricular assist device flow. We
      suggest that inhaled nitric oxide is a useful adjunctive treatment that should be
      routinely available at the time of left ventricular assist device implantation.

PMID- 9563610
TI  - Situs inversus donor heart successfully transplanted.
AB  - Orthotopic heart transplantation was successfully performed in a 62-year-old man
      by use of a heart harvested from a donor with situs inversus. This procedure is a
      reasonable alternative when no other donor is available. The technique of this
      operation is described here. A month later the patient was discharged in good
      condition and is still doing well 1 year after the transplantation.

PMID- 9563611
TI  - Scedosporium apiospermum (Pseudallescheria boydii) infection in a heart
      transplant recipient: a case of mistaken identity.
AB  - We report a case of fatal central nervous system infection with Scedosporium
      apiospermum (Pseudallescheria boydii) in a heart transplant recipient. This
      ubiquitous fungus is known to cause mycetoma and localized infections in patients
      with otherwise normal conditions. Disseminated infections occur rarely and are
      seen primarily in patients who are receiving immunosuppressive medications or who
      have neutropenia. Often life-threatening when infection is disseminated and
      involves the central nervous system, this diagnosis is difficult to make rapidly
      because S. apiospermum (P. boydii) mimics Aspergillus spp. and Fusarium spp.,
      both clinically and histopathologically. Imidazoles such as miconazole, but not
      amphotericin B, are considered the therapeutic compounds of choice. Improved
      diagnostic and treatment options are needed to optimize management of infections
      with S. apiospermum (P. boydii).

PMID- 9563612
TI  - Extracorporeal membrane oxygenation support for single lung transplantation in a
      patient with primary pulmonary hypertension.
AB  - Left single lung transplantation was performed under perioperative extracorporeal
      membrane oxygenation (ECMO) support for a patient of primary pulmonary
      hypertension. Continuous ECMO in this patient for one day after the
      transplantation decreased the pulmonary blood flow and probably served to
      minimize the potential complication of reperfusion edema of the graft. During
      this period, the ECMO was gradually weaned so that the grafted lung could adapt
      itself to the gradually increased blood flow through it. The patient was
      extubated without difficulty 2 days alter the removal of ECMO and made a smooth
      recovery.

PMID- 9563613
TI  - Removal and repositioning of "permanent" expandable wire stents in bronchial
      airway stenosis after lung transplantation.
AB  - Significant airway stenosis occurs in 7% to 14% of lung transplant recipients.
      The use of permanent, nonadjustable, wire mesh stents can be of concern in the
      transplant recipient with nonmalignant stricture. We report the replacement and
      repositioning of an expandable wire mesh stent in a double lung transplantation
      with distal bronchial stenosis.

PMID- 9563614
TI  - Malignancy transplantation with heart graft.

PMID- 9563615
TI  - Ground reaction forces in Greyhounds with tibial nerve injury.
AB  - OBJECTIVES: To measure ground reaction force variables during lameness resulting
      from impaired tibial nerve function and to determine whether these variables
      changed significantly as recovery progressed. ANIMALS: 11 healthy Greyhounds of
      either sex, weighing between 22 and 39 kg. PROCEDURE: On 3 consecutive days
      before surgery, ground reaction forces were measured by force platform gait
      analysis at the trot. In dogs under general anesthesia, the left tibial nerve was
      crushed proximal to innervation of the gastrocnemius muscle. Gait analyses were
      repeated on days 8 to 10, 28 to 30, 43 to 45, 58 to 60, and 90 to 92 after
      surgery. Ground reaction force variables and stance time were compared among the
      3-day clusters. RESULTS: 10 days after surgery, all dogs had weight-bearing
      lameness attributed to paralysis of muscles in the caudal compartment of the
      crus. Nerve regeneration resulted in functional recovery within 3 months.
      Decreases in vertical force were significant 10 days after surgery; thereafter,
      changes reflected gradual return of load bearing, with the most marked
      improvement between 10 and 45 days. At 90 days, vertical force variables were
      within 3% of presurgical values. Stance time for the left hind limb was
      significantly longer at 10, 30, and 45 days after surgery and was seen in all
      dogs, but returned to within 1 % of preoperative stance time at 90 days. The
      effect of tibial nerve dysfunction on braking or propulsive force was not
      significant. CONCLUSIONS AND CLINICAL RELEVANCE: The significant changes in
      vertical ground reaction forces in hind limbs of dogs during lameness that
      resulted from impaired tibial nerve function are detectable, as is response
      during recovery, by use of force platform analysis.

PMID- 9563616
TI  - Evaluation of the morphologic characteristics and prevalence of canine
      urocystoliths from a regional urolith center.
AB  - OBJECTIVE: To determine whether morphology of single-mineral urocystoliths and
      age, sex, or breed data could be applied to facilitate radiographic and clinical
      urocystolith mineral type prediction, respectively, in dogs. SAMPLE POPULATION:
      Database of 2,041 dogs with pure mineral composition urocystoliths. PROCEDURE:
      All uroliths were characterized according to geologic descriptive terminology and
      by breed, sex, and age of dog at time of sample submission. Summary statistics
      were used to compare features with specific mineral types. Observed trends were
      analyzed for statistical relevance between observed and expected frequencies for
      age, sex, color, size, shape, and surface, using the null hypothesis that
      differences by urocystolith mineral type did not exist. On the basis of expected
      breed occurrence derived by equations, the null hypothesis that urocystolith
      occurrence paralleled canine breed popularity was tested. RESULTS: Urocystoliths
      > 10 mm in any dimension were > 92% likely to be magnesium ammonium phosphate
      hexahydrate (MAP). Smooth, blunt-edged or faceted, and pyramidal urocystoliths
      were usually MAP. Jackstone shapes were almost always silica. Botryoidal (grape
      like clusters) urocystoliths were likely to be oxalates. Breeds with high
      relative likelihood of urocystoliths included: English Bulldog, Pekingese, Pug,
      Welsh Corgi, and West Highland White Terrier. Breeds with low relative likelihood
      of urocystolith production included: German Shepherd Dog, Shar-Pei, and German
      Shorthaired Pointer. About 94% of urocystoliths produced in females or spayed
      females were MAP, whereas males and neutered males produced a greater assortment.
      CONCLUSIONS AND CLINICAL RELEVANCE: For pure mineral composition urocystoliths,
      trends in mineral type among breeds and between sexes can be exploited clinically
      in the diagnosis and management of urolith-related disease. Size and shape, used
      in conjunction with age, breed, and sex, can facilitate pure urocystolith mineral
      type prediction.

PMID- 9563618
TI  - Evaluation of platelet activation and platelet-neutrophil aggregates in
      Thoroughbreds undergoing near-maximal treadmill exercise.
AB  - OBJECTIVES: To determine whether platelets become activated and form platelet
      neutrophil aggregates during near-maximal treadmill exercise in horses. ANIMALS:
      4 Thoroughbreds. PROCEDURE: Horses were subjected to 4 standardized exercise
      tests on a treadmill, and blood samples were collected before exercise, at
      treadmill speed of 12 m/s, and 5 minutes after exercise. Flow cytometric
      techniques were used to identify activated platelets, and flow cytometric and
      microscopic techniques were used to identify platelet-neutrophil aggregates.
      RESULTS: Platelet-neutrophil aggregates increased from 2.8 +/- 0.4% at rest to
      17.2 +/- 1.1% and 14.7 +/- 1.6% during and after exercise, respectively. Platelet
      activation was not detected during or after exercise. CONCLUSIONS: Platelet
      neutrophil aggregates consistently form during strenuous exercise in horses.

PMID- 9563617
TI  - Scintigraphic assessment of gastric emptying of canned and dry diets in healthy
      cats.
AB  - OBJECTIVE: To characterize factors that affect solid-phase gastric emptying in
      healthy cats by use of nuclear scintigraphy and to assess differences in emptying
      patterns of dry and canned diets. ANIMALS: 20 healthy cats. PROCEDURE: 2 groups
      of 10 cats each were fed dry or canned diet for at least 2 weeks before
      scintigraphy was done. Diets were labeled with 99mTc-disofenin. After ingestion
      of labeled meals, scintigraphic images were obtained at 0, 15, 30, 45, and 60
      minutes, then every 30 minutes to 6 hours. Gastric emptying scans were obtained 3
      times for each cat for each diet, in a complete crossover design. The T90, T50,
      and T20 (times when 90, 50, and 20% of initial meal activity remained in the
      stomach, respectively) were derived from gastric emptying curves fit to nonlinear
      models. A mixed models approach was used for data analysis. RESULTS: Gastric
      emptying was well described by a nonlinear model. Meal size, water intake, and
      diet type significantly (P < 0.05) effected gastric emptying. The T90, T50, and
      T20 increased with meal size, regardless of diet type or water intake. Gastric
      emptying of a dry diet meal took significantly (P < 0.05) longer than that of an
      isocaloric meal of canned diet, except when meal size was small. Differences in
      gastric emptying of dry and canned diets varied with the phase (T90 vs T50 vs
      T20) of emptying. CONCLUSION: Water intake, meal size, and diet type
      significantly influence gastric emptying in healthy cats, and these factors must
      be considered in analysis of gastric emptying data.

PMID- 9563619
TI  - Use of an in vitro biotinylation technique for determination of posttransfusion
      viability of stored canine packed red blood cells.
AB  - OBJECTIVE: To determine posttransfusion viability (PTV) of canine RBC stored for
      35 days in an additive solution, using in vitro biotinylation and technetium-99m
      and chromium-51 (99mTc/51Cr) labeling techniques. SAMPLE POPULATION: 6 random
      source, adult dogs. PROCEDURE: RBC from dogs were labeled with N
      hydroxysuccinimide biotin (NHS-biotin) or 99mTc/51Cr in a crossover design. One
      unit (450 ml) of whole blood was collected from each dog, processed into packed
      RBC, and stored for 35 days in an additive solution. The process was repeated at
      a later date, so that each dog had 2 units stored under similar conditions.
      Stored autologous RBC were then labeled with either NHS-biotin or 51Cr and
      reinfused. When 51Cr was used, labeled cells were infused simultaneously with
      freshly drawn cells labeled with 99mTc. Posttransfusion viability of labeled
      cells was determined by dividing counts per minute (99mTc/51Cr) or percentage of
      cells (NHS-biotin) labeled at 24 hours by counts per minute or percentage of
      cells labeled after infusion. RESULTS: Mean PTV of packed RBC stored for 35 days
      in an additive system was 80% when determined by biotinylation, 83% as determined
      by 99mTc/ 51Cr, and 81% as determined by 51Cr alone. CONCLUSIONS: In vitro
      biotinylation provides an acceptable, nonradioisotopic means of determining PTV
      of stored canine packed RBC. CLINICAL RELEVANCE: NHS-biotin can be used to
      determine maximal storage time of canine RBC prepared for transfusion purposes.

PMID- 9563620
TI  - Rapid spread of a unique strain of Pasteurella haemolytica serotype 1 among
      transported calves.
AB  - OBJECTIVE: To determine the rate and mode of infectious spread of Pasteurella
      haemolytica among calves maintained under typical conditions during collection,
      transport, and the first month of feeding. ANIMALS: 101 two- to five-month-old
      Angus-crossbred calves. PROCEDURE: Samples obtained from cattle prior to and
      after they were transported to a feedlot were used for isolation and
      characterization of P haemolytica. Samples were also obtained from additional
      calves, some of which were sick, and these calves were then commingled with the
      transported calves for 3 days. A strain of P haemolytica that contains a rare
      deletion of the 4.2-kilobase streptomycin- and sulfonamide-resistance plasmid was
      inoculated into both palatine tonsils of 12 calves. Nasal secretions were
      aspirated from the ventral nasal meatus. Tonsillar wash specimens were procured.
      Pasteurella haemolytica organisms were quantitatively cultured and identified on
      the basis of colony morphology and response to specific antisera. Plasmids were
      isolated by an alkaline lysis procedure and identified by agarose gel
      electrophoresis. RESULTS: A single plasmid profile was observed from P
      haemolytica isolated from samples obtained prior to shipment. Commingled calves
      were shedding P haemolytica containing each known plasmid profile. After
      shipment, samples contained P haemolytica isolates with each known plasmid
      profile. The plasmid profile of the unique P haemolytica isolate was recovered
      from all 12 inoculated calves and 10 other calves. Some calves simultaneously
      shed P haemolytica isolates with differing plasmid profiles. CONCLUSIONS AND
      CLINICAL RELEVANCE: Pasteurella haemolytica serotype 1 was horizontally
      transmitted among calves within days of commingling, which continued after calves
      were transported to a feedlot.

PMID- 9563621
TI  - Characterization of plasma immunoglobulin G concentrations of llamas.
AB  - OBJECTIVE: To develop appropriate reference ranges for plasma IgG concentrations
      of llamas. ANIMALS: 643 llamas on 5 farms. PROCEDURE: Plasma IgG concentration
      was measured by using a single radial immunodiffusion assay kit. Farm of origin,
      age, body condition score, and sex were recorded for each llama. The effect of
      each factor on plasma IgG concentration was evaluated separately, using ANOVA;
      the association between age and IgG concentration was evaluated, using linear
      regression. Multivariable regression models were developed to examine concurrent
      effects of age, sex, body condition score, farm, and various interactions on IgG
      concentration. RESULTS: The IgG concentrations were between 127 and 3,969 mg/dl.
      In llamas < 12 months old, farm of origin accounted for 29% of variability for
      IgG concentration. Reference range for plasma IgG concentrations in llamas < 12
      months old was 391 to 2,357 mg/dl; for llamas > 12 but < 28 months old was 771 to
      2,796 mg/dl; and for llamas > 28 months old was 570 to 3,264 mg/dl. These ranges
      were applicable only for the kit used in this study. CONCLUSIONS: Healthy llamas
      have a wide range of IgG concentrations. Determinants of IgG concentration are
      multifactorial, and their importance varies with age of the llamas. CLINICAL
      IMPLICATIONS: The wide range of IgG concentrations observed in healthy llamas and
      the influence that age and farm may have on IgG concentrations indicate that a
      result for one specific llama should be interpreted in relation to those of its
      herdmates.

PMID- 9563622
TI  - Evaluation of serologic responses, lymphocyte proliferative responses, and
      clearance from lymphatic organs after vaccination of bison with Brucella abortus
      strain RB51.
AB  - OBJECTIVE: To evaluate clearance of the vaccine strain, immunologic responses,
      and potential shedding of Brucella abortus strain RB51 organisms after
      vaccination of bison calves. ANIMALS: Fourteen 7-month-old female bison calves.
      PROCEDURE: 10 bison calves were vaccinated SC with 1.22 x 10(10) colony-forming
      units of B abortus strain RB51. Four bison calves were vaccinated SC with 0.15M
      NaCl solution. Rectal, vaginal, nasal, and ocular swab specimens were obtained to
      evaluate potential shedding by vaccinated bison. The superficial cervical lymph
      node was biopsied to evaluate clearance of the vaccine strain. Lymphocyte
      proliferative responses to strain RB51 bacteria were evaluated in lymph node
      cells obtained from biopsy specimens and also in peripheral blood mononuclear
      cells. RESULTS: Strain RB51 was recovered from superficial cervical lymph nodes
      of vaccinates examined 6, 12, and 18 weeks after vaccination (4/4, 3/4, and 1/4,
      respectively) but not in vaccinates examined at 24 weeks (0/3) after vaccination
      or nonvaccinates examined at all sample collection times (n = 1 bison/sample
      period). Serologic, immunologic, and bacterial culture techniques failed to
      reveal shedding of strain RB51 by vaccinates or infection of nonvaccinated bison.
      Lymphocyte proliferative responses were evident in lymph node cells and blood
      mononuclear cells from strain RB51-vaccinated bison beginning 12 weeks after
      vaccination. CONCLUSION: Strain RB51 was cleared from bison by 18 to 24 weeks
      after vaccination. Bison vaccinated with strain RB51 did not shed the vaccine
      strain to nonvaccinated bison housed in close proximity. Strain RB51 did not
      induce antibody responses in bison that would interfere with brucellosis
      surveillance tests, but did stimulate cell-mediated immunity.

PMID- 9563623
TI  - Prevention of fatal salmonellosis in neonatal calves, using orally administered
      chicken egg yolk Salmonella-specific antibodies.
AB  - OBJECTIVE: To protect neonatal calves against fatal salmonellosis within the
      first 2 weeks after birth, using chicken egg yolk antibodies specific against
      Salmonella typhimurium or S dublin. ANIMALS: 38 neonatal Holstein calves from
      Salmonella-free farms. PROCEDURE: After removal of the lipid components with
      hydroxypropylmethylcellulose phthalate, egg yolk antibodies were spray dried. At
      4 days of age, calves were challenge exposed by oral inoculation with 10(11)
      virulent S typhimurium (experiment 1) or S dublin (experiment 2). Starting from
      the challenge-exposure day, egg yolk antibody preparations were administered
      orally 3 times a day for 7 to 10 days. RESULTS: In passive immunization trials,
      the orally administered antibodies conferred dose-dependent protection against
      infection with each of the homologous strains of Salmonella. Within 7 to 10 days
      after challenge exposure, all control calves died, whereas low-titer antibody
      treated calves had 60 to 100% mortality. Only fever and diarrhea, but no deaths
      (P < 0.01), were observed in calves given the highest titer of antibody.
      CONCLUSIONS AND CLINICAL RELEVANCE: Compared with that in control calves,
      survival was significantly higher among calves given antibodies with titers of
      500 (P < 0.05) and 1,000 (P < 0.01) homotypic for S typhimurium and with titer of
      5,000 (P < 0.01) for S dublin. Egg yolk antibodies specific for whole cell S
      typhimurium or S dublin are protective against fatal salmonellosis when given in
      sufficiently high concentration, and may be clinically useful during a
      salmonellosis outbreak.

PMID- 9563624
TI  - Effects of stress resulting from short-term restraint on in vitro functional
      capacity of leukocytes obtained from pigs.
AB  - OBJECTIVE: To investigate whether the procedure used to snare and restrain pigs
      during collection of blood samples would alter in vitro functional capacity of
      leukocytes in the samples. ANIMALS: 8 gilts. PROCEDURE: Catheters were surgically
      inserted into the jugular vein of gilts to enable blood sample collection without
      restraint. After collection of a control sample, gilts were restrained by use of
      a snare and samples were collected at 0.5, 3.5, and 6.5 minutes after start of
      restraint (0 minutes). At each time point, plasma beta-endorphin and cortisol
      concentrations as well as WBC counts were recorded, and functional capacity of
      leukocytes in cultures of whole blood was assessed by means of mitogen-induced
      proliferation and interleukin-2 activity, virus-induced interferon-alpha
      concentration, and phagocytosis of zymosan particles. RESULTS: Concentrations of
      plasma beta-endorphin and cortisol were increased at 3.5 and 6.5 minutes after
      start of restraint. At these times, virus-induced interferon-alpha concentration
      was decreased, whereas proliferative response to Concanavalin A and
      phytohemagglutinin increased in samples collected at 6.5 minutes. CONCLUSION AND
      CLINICAL RELEVANCE: It was possible to snare pigs for the purpose of collecting
      blood samples and restrain them without causing excessive stress that would
      affect immunologic variables, provided that the collection procedure was
      completed within a few minutes.

PMID- 9563625
TI  - Development and testing of a unique strain of Pasteurella haemolytica for use in
      studies on colonization of the respiratory tract of cattle.
AB  - OBJECTIVE: To develop a unique strain of Pasteurella haemolytica, selectable from
      nasopharyngeal respiratory tract secretions, that retains the ability to
      efficiently colonize the respiratory tract of calves. ANIMALS: 26 calves that
      each weighed approximately 200 kg. PROCEDURE: Rifampicin-resistant mutants of P
      haemolytica were developed and tested for in vitro growth rate and leukotoxin
      production. After instillation into the tonsils of calves, an isolate that was
      efficient at colonizing was selected and transformed, using electroporation, with
      a 4.2-kilobase (kb) plasmid encoding for streptomycin resistance. This isolate
      was instilled into the tonsils of 4 of 14 commingled calves to examine
      transmission of organisms. Nasal secretion and tonsil wash specimens were
      collected, cultured, and examined for P haemolytica. Serum antibody concentration
      was measured by means of indirect hemagglutination. RESULTS: Selected P
      haemolytica organisms colonized the tonsils and nasal passages for more than 2
      weeks. Exposed calves and contact calves shed the organism, which was recovered
      from specimens of nasal secretions and tonsil washes. The 4.2-kb plasmid was lost
      during in vivo colonization. CONCLUSIONS AND CLINICAL RELEVANCE: The selected
      rifampicin-resistant P haemolytica organism colonized tonsils and nasal passages
      in a manner similar to the wild-type organisms. Selective media suppressed other
      bacterial flora to the extent that a single colony-forming unit was detectable
      from 200 microl of specimen, a 100-fold improvement in detection sensitivity. The
      selectable strain spread rapidly among commingled calves. A 4.2-kb plasmid marker
      was unstable when P haemolytica replicated in vivo.

PMID- 9563626
TI  - Bacterial flora in the duodenum of healthy cats, and effect of dietary
      supplementation with fructo-oligosaccharides.
AB  - OBJECTIVE: To investigate changes in the duodenal flora of healthy cats over
      time, and evaluate the effect of dietary supplementation with fructo
      oligosaccharides (FOS). ANIMALS: 12 healthy, barrier-maintained, specific
      pathogen-free cats. PROCEDURE: Duodenal juice for bacteriologic examination was
      collected via oral endoscopy 5 times from each cat over a 32-week period. Cats
      were allotted randomly to 2 groups, and a crossover design study, during which
      they were fed either a replete dry (basal) diet or, for 12 consecutive weeks,
      basal diet supplemented with 0.75% FOS, was done. Samples (3 from cats fed the
      basal and 2 from cats fed the FOS diet) were collected for a minimum of 6 weeks
      after commencement of feeding, and a minimum of 6 weeks apart. RESULTS: Mean
      aerobic, anaerobic, and total bacterial counts did not differ significantly among
      sample collection times. After pooling of the results, mean (+/- SD) log10 colony
      forming units (CFU) of aerobic, anaerobic, and total bacteria/ml were 5.5 +/-
      1.1, 4.8 +/- 1.0 and 5.6 +/- 1.1, respectively. However, individual cats had
      considerable variation in counts: mean (range) intraindividual coefficients of
      variation were: 19.0 (6.1 to 34.2), 19.9 (4.8 to 35.5), and 18.1 (5.5 to 32.6)%,
      respectively. In 1 cat, total bacterial count varied between < 3.0 and 6.3
      CFU/ml. Bacterial flora varied qualitatively: only Enterococcus faecalis,
      Clostridium perfringens, Bacteroides, Pasteurella, and Streptococcus spp, and
      unidentified gram-negative (aerobic) rods were present in > 50% of the samples.
      CONCLUSIONS: Wide quantitative and qualitative variation in the duodenal flora of
      healthy cats was observed over time, which was not affected by dietary
      supplementation with FOS.

PMID- 9563627
TI  - Effect of dietary supplementation with fructo-oligosaccharides on fecal flora of
      healthy cats.
AB  - OBJECTIVE: To investigate changes in the fecal flora of healthy cats after
      dietary supplementation with fructo-oligosaccharides (FOS). ANIMALS: 12 healthy,
      barrier-maintained, specific-pathogen-free-derived adult cats. PROCEDURE: Fresh
      fecal samples for quantitative and qualitative bacteriologic examination were
      collected from each cat after ingestion of a replete dry (basal) diet for a
      minimum of 8 weeks. The diet was then supplemented with 0.75% FOS, and another
      fecal sample was collected after 12 weeks. RESULTS: Mean +/- SD fecal aerobic,
      anaerobic, and total bacterial counts (log10 colony-forming units per gram of
      feces [CFU/g]) did not differ significantly between diets (8.3 +/- 0.8, 9.2 +/-
      0.6, 9.4 +/- 0.4, respectively, for the basal diet; and 8.4 +/- 0.8, 9.7 +/- 0.7,
      and 9.8 +/- 0.7, respectively, for the FOS diet), although there was a trend for
      higher numbers of anaerobes and total bacteria associated with the FOS diet.
      Members of the genus Bacteroides, Clostridium perfringens, Escherichia coli,
      lactobacilli, and Plesiomonas shigeloides were the most prevalent bacteria
      isolated. Compared with samples from cats fed basal diet, there was a trend for
      increased mean counts of lactobacilli (P = 0.02) and Bacteroides spp (P = 0.05)
      after FOS supplementation, and a trend for decreased mean numbers of Escherichia
      coli (P = 0.03) and Clostridium perfringens (P = 0.08) to be associated with the
      FOS diet. Supplementation of FOS resulted in a median 164-fold increase in
      numbers of lactobacilli, 13.2-fold increase in Bacteroides spp, 98% reduction in
      numbers of C perfringens, and 75% reduction in numbers of E coli. CONCLUSIONS:
      Supplementation of the diet with FOS resulted in alteration of the fecal flora of
      cats.

PMID- 9563628
TI  - Oral inoculation of cats with tissue cysts of Neospora caninum.
AB  - OBJECTIVE: To test the hypothesis that cats are definitive hosts of Neospora
      caninum. ANIMALS: 6 weaned male kittens obtained from 2 sources, and several
      dozen outbred mice. PROCEDURE: Cats were fed large numbers of 3 strains of N
      caninum: tissue cysts in buffered saline solution, mouse brain homogenates, and
      whole carcass homogenates from seropositive mice. Fecal specimens were examined
      for 4 weeks by use of flotation tests, and bioassays were performed in mice. One
      cat was inoculated parenterally with tachyzoites, to determine whether cats could
      respond serologically to N caninum. Tissue cysts from portions of oral inocula
      were cultured to verify viability. Indirect fluorescent antibody serologic
      testing, histologic and immunohistologic examinations, cell culture, and
      polymerase chain reaction procedures were performed 4 to 8 weeks after oral
      exposure, to seek evidence of infection of cats and mice. RESULTS: None of the
      cats or mice seroconverted to N caninum, with the exception of the single cat
      inoculated parenterally. Fecal shedding of oocysts was not observed, except for
      Isospora felis oocysts that were shed by 2 cats beginning prior to oral challenge
      exposure. Evidence of infection was not detected in tissues of cats or mice, with
      the exception of the parenterally inoculated cat. CONCLUSIONS: The hypothesis
      that cats are definitive hosts of N caninum is not supported. CLINICAL RELEVANCE:
      Extermination of cats in efforts to control bovine neosporosis is not warranted.

PMID- 9563630
TI  - Effect of infusion of hypertonic saline solution of conscious heifers with
      hypoxemia caused by endotoxin infusion.
AB  - OBJECTIVE: To compare effects of i.v. infusion of a small volume (5 ml/kg of body
      weight) of hypertonic saline (7.2% NaCl) solution (HSS) and i.v. infusion of an
      equivalent volume of isotonic saline (0.9% NaCl) solution (ISS) on arterial blood
      gases in conscious heifers with hypoxemia caused by endotoxin infusion. ANIMALS:
      9 Holstein heifers. PROCEDURE: All heifers received 2.0 microg of endotoxin/kg,
      i.v., during a 5-minute period. Twenty-five minutes after endotoxin infusion, 3
      heifers received ISS, 3 received HSS, and the remaining 3 did not receive fluids
      (control). Heifers were monitored for 150 minutes after initiation of fluid
      replacement. Arterial blood gases, blood pressure, and serum electrolyte
      concentrations were measured. RESULTS: Endotoxin administration had a profound
      effect on pulmonary function, causing severe hypoxemia accompanied by a
      significant decrease in the partial pressure of oxygen (PaO2) and a significant
      increase in the arterial-alveolar O2 gradient (P[A-a]O2). Cattle in the HSS group
      had progressive and significant increases in PaO2 and O2 saturation, compared
      with the other groups. The P(A-a)O2 values for the control and ISS groups were
      slightly decreased until 150 minutes after initiation of fluid replacement;
      however, HSS infusion induced a progressive and significant decrease in P(A-a)O2
      for the remainder of the experimental period. CONCLUSIONS AND CLINICAL RELEVANCE:
      Rapid infusion of HSS can successfully resuscitate conscious cattle with induced
      pulmonary dysfunction. Infusion of HSS may be beneficial for initial
      resuscitation of cattle with naturally developing bovine respiratory disease
      complex.

PMID- 9563629
TI  - Signaling pathways for tissue factor expression in lipopolysaccharide-stimulated
      bovine alveolar macrophages.
AB  - OBJECTIVE: To investigate receptor-mediated intracellular events in bovine
      alveolar macrophages (AM) stimulated by bacterial lipopolysaccharide (LPS), using
      tissue factor (TF) expression as the measurable functional endpoint. SAMPLE
      POPULATION: Pulmonary AM harvested from 1- to 4-month-old male Holstein calves.
      PROCEDURE: Alveolar macrophages, acquired by use of volume-controlled
      bronchopulmonary lavage, were treated with CD14 monoclonal antibody (20
      microg/ml), pertussis toxin (300 ng/ml), or 1 of 3 known protein kinase C (PKC)
      inhibitors (10 microM chelerythrin, 100 microM H-7, or 50 nM staurosporin), then
      were stimulated with LPS alone (0.01, 0.10, 1.0, 10.0 microg/ml) or LPS (0.25,
      0.5, 1.0 ng/ml) in combination with concentrated bovine serum fraction 2 (500
      ng/ml). Tissue factor expression was quantified by use of a colorimetric assay.
      Changes in intracellular Ca2+ concentration and pH were monitored, using Ca2+-
      and pH-sensitive fluorescent dyes, with changes in fluorescent intensity after
      incubation with LPS measured by spectrophotometry. RESULTS: Treatment of AM with
      a CD14 monoclonal antibody caused profound inhibition of TF expression (P <
      0.0001) after stimulation by LPS combined with bovine serum fraction 2. Pertussis
      toxin had a significant (P < 0.0319) inhibitory effect on TF expression when
      cells were stimulated by LPS alone. Treatment with all 3 PKC inhibitors caused
      marked reduction in TF expression of cells stimulated with LPS alone or with
      phorbol myristate acetate. Stimulation of cells by LPS failed to mobilize
      intracellular Ca2+ stores or to alter cytosolic pH. CONCLUSION: LPS combined with
      serum factors binds to CD14 on the surface of AM, and PKC is an important
      signaling kinase in the pathway utilized by LPS, resulting in enhanced TF
      expression; a pertussis toxin-sensitive G protein is involved in the signaling
      pathway utilized by LPS alone; and mobilization of Ca2+ does not have a role in
      the signal transduction pathway utilized by LPS nor does LPS affect cytosolic pH
      of AM.

PMID- 9563631
TI  - Pharmacokinetics of cefepime and comparison with those of ceftiofur in horses.
AB  - OBJECTIVE: To determine pharmacokinetics of i.v., i.m., and oral administration
      of cefepime in horses and to compare pharmacokinetics of i.m. administration of
      cefepime with those of ceftiofur sodium. ANIMALS: 6 clinically normal adult
      horses. PROCEDURE: Horses received 3 doses of cefepime (11 mg/kg of body weight,
      PO; 2.2 mg/kg, i.v.; and 2.2 mg/kg, i.m.) and 1 dose of ceftiofur (2.2 mg/kg,
      i.m.). Two horses also received L-arginine, p.o. and i.v., at doses identical to
      those contained in the cefepime dihydrochloride-L-arginine preparations
      previously administered. Blood samples were collected for 24 hours after
      administration of cefepime or ceftiofur and were assayed for cefepime and
      ceftiofur concentrations. RESULTS: Pharmacokinetic analysis of disposition data
      indicated that i.v. administration data were best described by a 2-compartment
      open model, whereas i.m. administration data were best described by a 1
      compartment absorption model. Median elimination half-life and volume of
      distribution after i.v. administration of cefepime were 125.7 minutes and 225
      ml/kg, respectively. After i.m. administration of cefepime, mean maximal plasma
      concentration of (8.13 microg/ml) was reached at a mean time of 80 minutes.
      Absorption of cefepime after i.m. administration was complete, with a median
      bioavailability of 1.11. Intramuscular administration of ceftiofur resulted in
      similar mean maximal plasma concentration (7.98 microg/ml) and mean time to this
      concentration (82 minutes). Cefepime was not detected in samples collected after
      oral administration. Adverse effects consisting principally of gastrointestinal
      disturbances were observed after oral and i.m. administration of cefepime and
      after 1 i.m. administration of ceftiofur. CONCLUSIONS AND CLINICAL RELEVANCE:
      Cefepime, administered i.v. or i.m. at a dosage of 2.2 mg/kg, every 8 hours is
      likely to provide effective antibacterial therapy for cefepime-sensitive
      organisms in horses. Further studies are needed to evaluate adverse effects on
      the gastrointestinal tract.

PMID- 9563632
TI  - Clinical and microbiological effects of controlled-release local delivery of
      minocycline on periodontitis in dogs.
AB  - OBJECTIVE: To evaluate the clinical and microbiological efficacy of minocycline
      in a subgingival local delivery system as an adjunct to tooth scaling and root
      planing in dogs with periodontal disease. ANIMALS: Nine 4- to 7-year-old Beagles
      with periodontitis. PROCEDURE: After scaling of teeth and root planing, 2
      treatment and 1 or 2 control sites were selected for each dog: treated sites (n =
      18) received minocycline hydrochloride periodontal formulation and control sites
      (n = 12) received ointment base (no minocycline). Gingival crevicular fluid was
      collected at a baseline (prior to treatment) and at week 4. Clinical and
      microbiological effects were evaluated and compared among sites. RESULTS: In
      minocycline-treated sites, clinical indices were significantly decreased at week
      4, compared with those at baseline. Minocycline-treated sites were associated
      with a significant decrease in gingival crevicular fluid, probing depth, and
      bleeding on probing values, compared with those for control sites at week 4.
      Compared with that for control sites, total bacteria count in periodontal pockets
      of minocycline-treated sites had an obvious tendency to decrease by week 4.
      Proportions of Porphyromonas and Fusobacterium spp were significantly decreased
      at week 4, compared with proportions at control sites and with pretreatment
      (baseline) values. CONCLUSIONS: When used as an adjunct to tooth scaling and root
      planing, minocycline periodontal formulation stimulated favorable clinical and
      antimicrobial responses.

PMID- 9563633
TI  - Influence of atipamezole on effects of midsacral subarachnoidally administered
      detomidine in mares.
AB  - OBJECTIVE: To examine effects of atipamezole on detomidine midsacral
      subarachnoidally-induced analgesia, cardiovascular and respiratory activity, head
      ptosis, and position of pelvic limbs in healthy mares. ANIMALS: 10 healthy mares.
      PROCEDURE: Using a randomized, blinded, crossover study design, mares received
      detomidine (0.03 mg/kg of body weight, diluted in 3 ml of CSF) midsacral
      subarachnoidally, followed by atipamezole (0.1 mg/kg [test]) or sterile saline
      (0.9% NaCl) solution (control), i.v. 61 minutes later and saline solution (3 ml,
      midsacral subarachnoidally) on a separate occasion, at least 2 weeks later.
      Analgesia was determined by lack of sensory perception to electrical stimulation
      at the perineal dermatome and no response to needle-prick stimulation extending
      from the coccygeal to T15 dermatomes. Arterial acid-base (pH, standard
      bicarbonate, and base excess values), gas tensions (PO2, PCO2), PCV, total solids
      concentration, heart and respiratory rates, rectal temperature, and arterial
      blood pressure were determined, and mares were observed for sweating and
      urination. Mean scores of perineal analgesia, head ptosis, position of pelvic
      limbs, and cardiovascular and respiratory data were compared for the 3-hour test
      period. RESULTS: Subarachnoidally administered detomidine induced perineal
      analgesia (mean +/- SD onset, 9.0 +/- 4.6 minutes; duration, 130 +/- 26 minutes),
      marked head ptosis, moderate changes in pelvic limb position, cardiovascular and
      respiratory depression, sweating in analgesic zones, and diuresis. Intravenously
      administered atipamezole significantly reduced mean scores of detomidine-induced
      perineal analgesia, head ptosis, pelvic limb position, sweating and diuresis;
      partially antagonized detomidine-induced bradycardia; and did not effect
      detomidine-induced bradypnea. CONCLUSIONS AND CLINICAL RELEVANCE: Most effects of
      midsacral subarachnoidally administered detomidine, except bradycardia and
      bradypnea, were reversed by atipamezole (0.1 mg/kg, i.v.), indicating that most
      of the actions of detomidine were mediated via activation of alpha2-adrenergic
      receptors.

PMID- 9563634
TI  - Comparison of isoflurane with sevoflurane for anesthesia induction and recovery
      in adult dogs.
AB  - OBJECTIVE: To compare mask anesthesia induction and recovery characteristics
      between 2 inhalant anesthetic agents: isoflurane and sevoflurane. ANIMALS: 16
      clinically normal, young adult Beagles. PROCEDURE: Using a cross-over design,
      dogs were randomly selected to receive sevoflurane or isoflurane via a face mask
      and a circle anesthetic system. Vaporizer setting concentrations were increased
      in stepwise, equal minimum alveolar concentrations (MAC) for each anesthetic
      until the vaporizer setting of 2.6% for isoflurane or 4.8% for sevoflurane (2
      MAC) was reached. Concentration was kept constant until the dog had a negative
      tail clamp response and was intubated. End-tidal concentration was maintained at
      1.8 to 2.0% or 3.3 to 3.8% for isoflurane or sevoflurane, respectively (1.4 to
      1.6 MAC) for 30 minutes. Dogs were allowed to recover with only tail clamp
      stimulation until a positive response was obtained. Extubation was performed when
      a spontaneous swallow reflex was observed. Dogs were allowed to achieve sternal
      recumbency and stand unassisted without further stimulation. RESULTS: Sevoflurane
      induction resulted in shorter time to loss of palpebral reflex, negative tail
      clamp response, and time to tracheal intubation, and was of better quality than
      isoflurane induction. Both anesthetics were associated with rapid and smooth
      recovery. CONCLUSIONS: Sevoflurane mask induction is faster and of better
      quality, compared with isoflurane, in adult dogs. Recovery time and quality are
      comparable. CLINICAL RELEVANCE: On the basis of these results, sevoflurane is a
      suitable inhalant anesthetic for mask induction and recovery in adult dogs and
      appears to have some advantages over isoflurane, including faster and smoother
      mask induction.

PMID- 9563635
TI  - Inhibition of pilocarpine-induced aqueous humor flare, hypotony, and miosis by
      topical administration of anti-inflammatory and anesthetic drugs to dogs.
AB  - OBJECTIVE: To investigate the mechanism by which pilocarpine causes increased
      aqueous humor (AH) flare, hypotony, and miosis in dogs. ANIMALS: 6 dogs with
      normal eyes. PROCEDURE: Both eyes of each dog were treated topically with a 2%
      solution of pilocarpine, and 1 eye of each dog was additionally treated with
      commercially available ophthamic solutions. Breakdown of the blood-aqueous
      barrier (BAB) was quantitated in each eye, using laser flaremetry to measure AH
      flare. Intraocular pressure and pupil size were also measured. RESULTS:
      Pilocarpine caused increased flare from BAB breakdown that was inhibited by the
      drugs tested. Inhibition (most to least) of BAB breakdown was flurbiprofen more
      than diclofenac, proparacaine, or suprofen, which were more than 0.125 or 1.0%
      prednisolone. Inhibition appeared dose-dependent and caused consensual inhibition
      in the contralateral eye. Intraocular pressure was decreased only in proparacaine
      treated eyes and increased in eyes treated with nonsteroidal anti-inflammatory
      drugs (NSAID). Flurbiprofen and proparacaine were the most effective at blocking
      miosis. CONCLUSIONS: Pilocarpine produced a predictable, reproducible BAB
      breakdown in dogs. Miosis and increased AH flare were inhibited equally by
      proparacaine or NSAID, suggesting that these signs were caused by neuropeptide
      release into the AH from antidromic stimulation, which subsequently triggers
      prostaglandin production. Hypotony was inhibited only by anti-inflammatory drugs.
      CLINICAL RELEVANCE: Proparacaine in combination with pilocarpine would be the
      best choice for treating dogs with acute glaucoma. Topical administration of
      NSAID should not be used to treat dogs with acute glaucoma, because they increase
      intraocular pressure and negate the effects of pilocarpine.

PMID- 9563636
TI  - Changes in plasma atrial natriuretic peptide concentration in exercising horses
      in relation to hydration status and exercise intensity.
AB  - OBJECTIVE: To investigate effects of hydration status and exercise intensity on
      plasma atrial natriuretic peptide (ANP) concentration in exercising horses.
      ANIMALS: 4 trained Standardbreds. PROCEDURE: Horses performed a 40-minute
      exercise test at 65 to 70% maximal heart rate (HRmax; no incline) and a 12-minute
      test at approximately 90% HRmax (3.5 degrees incline). The 40-minute test was
      performed with ad libitum access to drinking water (normohydration), after water
      had been withheld for 24 hours (dehydration), and 30 minutes after 12 L of water
      at body temperature had been given via nasogastric tube (hyperhydration). The 12
      minute test was only performed with normohydrated horses. RESULTS: Plasma ANP
      concentration was higher toward the end of exercise during hyperhydration than
      during the other 2 hydration states, and the area under the plasma ANP
      concentration curve was significantly greater during hyperhydration than during
      dehydration. The maximal plasma ANP value induced during the 12-minute test was
      similar to that of the 40-minute test. After the 12-minute test, plasma ANP
      concentration did not decrease during the first 30 minutes of recovery, whereas
      after the 40-minute test, plasma ANP concentration decreased by approximately 30%
      during the same period. CONCLUSIONS: Hydration status can affect plasma ANP
      concentration in horses during submaximal exercise. Maximal plasma ANP
      concentration was similar at the 2 exercise intensities studied, but the
      postexercise return to baseline values differed. CLINICAL RELEVANCE: Changes in
      hydration status can cause alterations in plasma concentration of ANP, one of the
      hormones involved in the control of cardiovascular functions during exercise.

PMID- 9563637
TI  - Vascular and transsynovial forces of the isolated stationary equine joint.
AB  - OBJECTIVE: To provide quantitative assessment of forces affecting filtration of
      synovial fluid in response to incremental changes in arterial and venous
      hemodynamics. ANIMALS: 7 clinically normal adult horses. PROCEDURE: Using a
      stationary, isolated metacarpophalangeal joint preparation, blood flow (Qa[cir]),
      tissue perfusion, arterial pressure (Pa[cir]), venous pressure (Pv[cir]),
      transsynovial fluid flow, total vascular resistance, vascular compliance, and
      tissue compliance were evaluated before and after arterial and venous pressure
      manipulations. At isogravimetric conditions, pre- and postcapillary resistance
      and ratios, osmotic reflection coefficient (sigma[d]), capillary pressure, net
      filtration pressure, and transitional microvascular pressure were determined.
      RESULTS: Synovial tissue blood flow was similar before, immediately after, and
      3.5 hours after joint isolation. The sigma(d) for the joint was low, owing to the
      high oncotic pressure of synovial fluid at filtration-independent states.
      Transsynovial flow occurred in preference to lymph flow because of the high
      permeability of synovial tissue (low sigma[d]). Synovial fluid production and
      transfluid flow (synovium weight gain) increased at Pa(cir) > 200 mm of Hg,
      indicating a threshold phenomenon for synovial filtration. Net filtration
      pressure > 6 mm of Hg is needed to effect an increase in synovial fluid flow, and
      pressure of approximately 11 mm of Hg is necessary to increase lymphatic flow.
      Vascular compliance in the joint was low, but increased markedly with Pv(cir).
      Vascular and tissue compliance increased with increased Pa(cir). Vascular
      compliance changes caused by increased arterial pressure were minimal, compared
      with those caused by increased venous pressure owing to the greater elastance of
      arteries and the larger muscular arterial wall. CONCLUSION: This isolated joint
      preparation permitted evaluation of codependent hemodynamic, microvascular, and
      transsynovial flow responses to hemodynamic manipulations. Synovial tissue
      permeability was markedly affected by increased vascular forces altering
      filtration pressures toward synovial fluid production.

PMID- 9563638
TI  - Effect of bilateral blockade of the pharyngeal branch of the vagus nerve on soft
      palate function in horses.
AB  - OBJECTIVE: To determine the effect of bilateral blockade of the pharyngeal branch
      of the vagus nerve on soft palate function in horses. ANIMALS: 5 Standardbreds.
      PROCEDURE: Peak tracheal inspiratory and expiratory pressures and airflow were
      measured while horses exercised at the speeds corresponding to 75 and 100% of the
      speed that resulted in maximal heart rate, with and without pharyngeal branch of
      the vagus nerve blockade. Respiratory frequency-to-stride frequency coupling
      ratio was measured by correlating foot fall measurements with respiratory
      frequency. The pharyngeal branch of the vagus nerve was blocked bilaterally as
      the nerve coursed through the auditory tube diverticulum (guttural pouch) across
      the longus capitus muscle. RESULTS: Persistent, reversible dorsal displacement of
      the soft palate (DDSP) occurred in all horses after nerve blockade, and lasted
      from 1 to 3 hours; normal nasopharyngeal function returned within 3 hours.
      Compared with control values, peak expiratory tracheal pressure increased (P =
      0.001), expiratory impedance increased (P = 0.007), and minute ventilation
      decreased (P = 0.04). Respiratory frequency-to-stride frequency coupling ratio
      decreased (P = 0.009) so that horses took 1 breath/stride without the nerve block
      and, approximately, 1 breath/2 strides with the block. CONCLUSION: DDSP creates
      flow-limiting expiratory obstruction and may be caused by neuromuscular
      dysfunction involving the pharyngeal branch of the vagus nerve. It may alter
      performance by causing expiratory obstruction and by altering breathing strategy
      in horses. CLINICAL RELEVANCE: A repeatable, reversible model of DDSP exists that
      allows further study of the disease. Dysfunction of the neuromuscular group,
      pharyngeal branch of the vagus nerve and palatinus and palatopharyngeus muscles,
      may be implicated in the pathogenesis of clinical DDSP.

PMID- 9563639
TI  - Cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine in
      clinically normal cats anesthetized with isoflurane.
AB  - OBJECTIVE: To assess the cardiovascular effects of the alpha2-adrenergic receptor
      agonist medetomidine in healthy cats anesthetized with 2% isoflurane. ANIMALS: 11
      clinically normal cats. PROCEDURE: Cats were anesthetized with isoflurane, and
      catheters were inserted for measurement of aortic, left ventricular, and right
      atrial pressures. For data collection, end-tidal isoflurane concentration was
      reduced to 2%, and end-tidal CO2 was maintained at 35 to 40 mm of Hg by use of
      positive-pressure ventilation. After measurement of baseline data, medetomidine
      (0.01 mg/kg of body weight, i.m.) was administered and data were collected
      continuously for 75 minutes. At the end of data collection, incisions were closed
      and cats were allowed to recover from anesthesia. RESULTS: Medetomidine
      significantly increased mean arterial pressure and systemic vascular resistance.
      The increase in mean arterial pressure was maximal at 17.8 +/- 7 minutes after
      medetomidine administration. Medetomidine also increased left ventricular peak
      systolic pressure, left ventricular end diastolic pressure, and right atrial
      pressure. Medetomidine significantly decreased heart rate and mean aortic flow.
      CONCLUSIONS: The low dosage of medetomidine (0.01 mg/kg, i.m.) promoted severe
      vasoconstriction in isoflurane-anesthetized cats, and resulted in sustained
      increases in left ventricular preload and afterload.

PMID- 9563640
TI  - Disparate chondrocyte metabolism in three-dimensional fibrin cultures derived
      from autogenous or commercially manufactured fibrinogen.
AB  - OBJECTIVE: To compare chondrocyte proliferation and metabolism in three
      dimensional fibrin cultures formed from polymerized autogenous fibrinogen with
      that of commercially manufactured fractionated fibrinogen. ANIMALS: Fibrinogen
      and chondrocytes for in vitro experimentation derived from 2 horses, ages 12 and
      14 months, donated for reasons unrelated to skeletal or hematologic
      abnormalities. PROCEDURE: Fibrinogen was isolated from whole blood, using plasma
      cryoprecipitation and centrifugation, and fractionated fibrinogen was purchased.
      Each was mixed with 10 x 10(6) chondrocytes/0.5 ml of fibrinogen, and was
      polymerized by addition of 0.5 ml of calcium-activated thrombin. Thirty 1-ml
      fibrin-chondrocyte disks were formed from each fibrinogen source and cultured for
      0 (n = 6), 7 (n = 12), or 14 (n = 12) days. Chondrocyte metabolism and cell
      proliferation in each fibrin type were objectively assessed by assays for total
      proteoglycan content, [35S]proteoglycan accumulation, proteoglycan monomer size,
      and total DNA. Cell morphology and cartilage-specific cell function was evaluated
      by routine histologic, alcian blue histochemical, type-II collagen
      immunohistochemical, and type-II collagen in situ hybridization methods. RESULTS:
      Histologic examination indicated better retention of chondrocyte morphology in
      autogenous composites. Autogenous fibrinogen also stimulated greater chondrocyte
      proliferation (DNA content increased 1.4-fold on day 14) and supported higher
      proteoglycan accumulation (increased 1.4-fold on day 14), compared with
      commercial, fractionated fibrinogen. Abundant intracellular type-II procollagen
      mRNA was detected in autogenous fibrin cultures by in situ hybridization, and
      translation was confirmed by extensive pericellular type-II collagen
      accumulation. CONCLUSIONS: Autogenous fibrinogen has an inherent capacity to
      maintain chondrocyte phenotypic metabolism that is reduced or absent in
      commercially prepared fibrinogen. Enhanced, differentiated cell function may be
      useful for in vivo applications, but represents an added variable that may
      confound in vitro experiments, and should be considered when designing studies of
      chondrocyte function.

PMID- 9563641
TI  - T-cell receptor-gamma rearrangement and c-myb methylation in MNNG-exposed Bloom
      syndrome B-lymphoblastoid cells.
AB  - The MNNG-exposed Bloom syndrome (BS) B-lymphoblastoid cell population (BS-MNNG),
      when analyzed for aberrant genetic variations, showed an illegitimate
      rearrangement at the TCR-gamma gene and hypermethylation at the c-myb
      protooncogene. The TCR-gamma rearrangement involved a Vgamma9 segment
      corresponding to a 4 kb band detected with a Jgamma-specific probe in HindIII
      digested DNA samples from BS-MNNG cells only. These variations were not shown by
      unexposed BS cells or both MNNG-exposed and unexposed normal (GA3) B
      lymphoblastoid cells.

PMID- 9563642
TI  - MNNG-transformed Bloom syndrome B-lymphoblastoids for the detection of Hodgkin's
      lymphoma-associated antigen in 2D Westerns.
AB  - Twenty-four hour MNNG-exposed Bloom syndrome (BS) B-lymphoblastoid cells with the
      potential to form single cell colonies in soft agar and nude mouse tumour (2/6
      (33%) showed a simultaneous increase in the Ras-expressing cells (using
      monoclonal antibody to p21 transforming protein) from 20% (at 24 h) to 85% (on
      day 30). In contrast, there was an absence of Ras-positive cells in MNNG-exposed
      fresh lymphocytes (PBMCs) from a healthy subject and a presence of only 11-18% of
      Ras-positive cells in normal (GA3) and unexposed BS B-lymphoblastoid cells. The
      Western blot analysis using sera samples from Hodgkin's lymphoma patients showed
      the presence of proteins of 102 and 68 kDa which in 2D Westerns were observed to
      be unique to BS-MNNG cells with approximate pIs of 5.3 and 5.7, respectively. It
      is proposed that BS-MNNG cells provide an interesting in vitro human cell model
      to generate unique cancer-associated antigen(s) in addition to using this system
      to understand the primary events associated with neoplastic transformation.

PMID- 9563643
TI  - Differential expression of protein kinase C isoforms in diethylnitrosamine
      initiated rat liver.
AB  - Although protein kinase C (PKC), a family of 12 related isoforms, plays an
      important role in carcinogenesis, little is known about the specific role of each
      isoform in the initiation stage of hepatocarcinogenesis. The subcellular
      distribution of PKC isoforms in the early stages of diethylnitrosamine (DEN)
      initiated hepatocarcinogenesis was therefore examined. Three-week-old female
      Sprague-Dawley rats were intraperitoneally injected twice in 1 week with DEN; all
      animals were sacrificed at 1, 2 and 24 h and 3 and 7 days after the second
      injection. PKCalpha and -beta expression in both cytosolic and particulate
      fractions decreased as a result of 1 h of DEN treatment and this effect lasted
      for 7 days. In both fractions, PKCepsilon expression showed a marked increase by
      DEN treatment, while the expression of PKCdelta and -zeta was almost unchanged.
      These results suggest that differential expression of PKC isoforms may play an
      important role in the early stage of DEN-initiated hepatocarcinogenesis in rats.

PMID- 9563644
TI  - Prevention of spontaneous and chemically-induced carcinogenesis using activated
      carbon fiber adsorbent. I. Effect of the activated carbon fiber adsorbent
      'Aqualen' on spontaneous carcinogenesis and life-span in mice.
AB  - Female SHR mice were fed the activated carbon fiber adsorbent Aqualen beginning
      at the age of 3 months through their life. Mice were fed Aqualen five times per
      week together with lab chow at a daily dose of 100 mg/kg b.w. The addition of
      Aqualen into food did not significantly influence the dynamics of body weight and
      the mean life-span of the animals. At the same time, the age at 90% mortality of
      mice was 4 months longer in the group exposed to Aqualen. There were no
      statistically significant differences in the incidence of all tumors and
      malignant tumors in the group of mice treated with Aqualen as compared with the
      control group. However, in the group of mice exposed to Aqualen, there was a 1.4
      times reduction of the mean number of tumors per mouse. Feeding mice with the
      adsorbent led to a 4 months longer life-span in animals with any tumors and to a
      5 months longer life-span in animals bearing malignant tumors (P < 0.05). No
      carcinogenic effect of Aqualen was found. It could be supposed that Aqualen has
      some geroprotective and anticarcinogenic properties.

PMID- 9563645
TI  - Cell cycle arrest and antitumor activity of pironetin and its derivatives.
AB  - The biological effects of pironetin and its derivatives on cell cycle progression
      and antitumor activity were studied. At 10-20 ng/ml, both pironetin and its
      demethyl derivative, NK10958P completely inhibited the cell proliferation of 3Y1
      cells, however, epoxypironetin showed only a weak inhibitory activity. The cell
      cycle analysis revealed that these compounds arrested the cell cycle progression
      at the M-phase in a dose-dependent manner. These antiproliferative effects of
      pironetin were also observed in the range 5-25 ng/ml with several tumor cell
      lines. In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal
      administration of 6.3 mg/kg pironetin over a 5-day period showed a moderate
      antitumor effect (T/C, 128%). As the chemical structure of pironetin is different
      from other M-phase inhibitors such as colchicine or vinblastine, pironetin will
      be the lead compound for a potential new antitumor drug.

PMID- 9563646
TI  - Expression of beta-catenin and gamma-catenin in epithelial tumor cell lines and
      characterization of a unique cell line.
AB  - In addition to its structural role, beta-catenin has recently been identified as
      an oncogene, while its homologue gamma-catenin (plakoglobin) seems to suppress
      tumorigenicity. Twenty-five epithelial tumor cell lines were screened; 18
      expressed both beta- and gamma-catenin, two expressed neither protein, four
      showed beta- but not gamma-catenin expression, while only one cell line showed
      gamma- but not beta-catenin expression. As per literature search, the cell line
      expressing gamma- but not beta-catenin appeared to be unique. This cell line,
      SKBR-3, is a human breast cancer cell line which does not express beta-catenin or
      E-cadherin protein. There is, however, expression of beta-catenin, but not E
      cadherin, mRNA. In order to determine the mechanism for this unique expression
      pattern, SKBR-3 cells were transfected with E-cadherin which resulted in
      expression of beta-catenin protein. Immunofluorescent staining of the E-cadherin
      transfected SKBR-3 cells revealed beta-catenin in the adherens junctions while
      transfection with just an epitope tagged (VSV) beta-catenin showed expression
      only in the nucleus. Double transfection with E-cadherin and VSV beta-catenin
      showed the beta-catenin in the adherens junction of the E-cadherin transfected
      cells. These results indicate that the mechanism for the lack of beta-catenin
      expression in the SKBR-3 cell line is possibly post-translational degradation and
      that when E-cadherin is transfected into these cells, the beta-catenin is
      stabilized in the adherens junction and not degraded. This cell line should be of
      interest to those studying the role of the homologues, beta- and gamma-catenin,
      in cancer pathogenesis.

PMID- 9563647
TI  - Cytotoxicity of heat-treated Korean mistletoe.
AB  - The cytotoxic effects of preparations of Korean mistletoe (Viscum album L. var.
      coloratum Ohwi) on non-tumorigenic A31 cells and tumorigenic MSV cells were
      investigated. While the aqueous extract from Korean mistletoe (<8 microg/ml)
      showed strong cytotoxicity on both cell lines, the heat-treated extract was much
      less cytotoxic with TD50 values of above 300 microg/ml. The heat-treated extract
      showed a growth-enhancing effect on non-tumorigenic cells and a cytotoxic effect
      on tumorigenic cells. The alkaloids fraction, which was isolated from the crude
      extract, was not cytotoxic to non-tumorigenic A31 cells up to 550 microg/ml, but
      was cytotoxic to tumorigenic MSV cells at 138 microg/ml. Heat treatment did not
      change the cytotoxic effects of the alkaloids fraction, indicating that the
      selective cytotoxicity of the heat-treated mistletoe extract on tumorigenic MSV
      cells might be due to its alkaloids. In order to study the changes in the
      cytotoxicity of fermented Korean mistletoe, the crude and heat-treated extracts
      were inoculated with Lactobacillus plantarum. During 7 days of fermentation, the
      cytotoxicity of the fermented heat-treated extract was increased while that of
      the fermented crude extract was not changed significantly.

PMID- 9563648
TI  - Involvement of EGF in medroxyprogesterone acetate (MPA)-induced mammary gland
      hyperplasia and its role in MPA-induced mammary tumors in BALB/c mice.
AB  - In previous papers we have demonstrated that sialoadenectomy inhibited MPA
      induced mammary tumorigenesis in BALB/c mice. To further explore the role of EGF
      in this experimental model, we evaluated its effects on mammary glands of
      sialoadenectomized (sialox) MPA-treated female mice and on tumor growth. MPA
      treated sialox mice were injected s.c. (n = 3) or not (n = 6) with 5 microg EGF
      every 36 h for 45 days; MPA-treated sham-operated mice were used as controls (n =
      6). Mammary glands from sialox MPA-treated mice are considerably less developed
      as compared with sham-operated animals. The exogenous administration of EGF
      restores the usual MPA-induced growth pattern of the glands, thus confirming a
      role for EGF either in mediating or cooperating with MPA in inducing the mammary
      architectural changes observed in MPA-treated mice. On the other hand, primary
      cultures of progestin-dependent (PD) ductal mammary adenocarcinoma in vivo tumor
      lines and of lobular progestin-independent (PI) tumor lines were used to evaluate
      the effect of EGF on tumor growth. In vitro EGF was found to stimulate cell
      proliferation of lobular PI tumor cells and of fibroblastic cells from both types
      of tumors at concentrations higher than 0.1-0.5 ng/ml and in the presence of 1-5%
      of charcoal-stripped fetal calf serum. Conversely, no proliferative effects were
      observed in ductal PD cells under the same experimental conditions, regardless of
      the presence of 10 nM MPA. It can be concluded that although EGF plays an
      important role in MPA-induced mammary carcinogenesis, it is not necessary in PD
      tumor growth.

PMID- 9563649
TI  - K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed
      to wood or leather dust.
AB  - Of 39 males diagnosed with sinonasal adenocarcinomas over 30 years in the Lund
      University Hospital catchment area (1.5 million inhabitants), archival tumor
      tissue was available from 29. Of these, 16 had been exposed to wood dust and
      three had been exposed to leather dust. The intestinal-type and papillary
      adenocarcinomas were more common in the exposed patients (P = 0.0002, Fisher's
      exact test). The tumors from all but one of the 29 sinonasal adenocarcinomas
      could be analyzed for point mutations at codons 12, 13 and 61 of the K-ras gene.
      Four mutations were detected in the 28 tumors. The three mutations in the
      patients exposed to wood and leather dust were all G:C --> A:T transitions, with
      two at position 2 of codon 12 and one at position 2 of codon 13. The high
      proportion of G:C --> A:T mutations in this rare tumor may reflect a genotoxic
      agent in wood and leather dust.

PMID- 9563650
TI  - Metal-mediated oxidative DNA damage induced by nitro-2-aminophenols.
AB  - Two hair dye components, carcinogenic 4-nitro-2-aminophenol and 5-nitro-2
      aminophenol, induced Cu(II)-dependent DNA cleavage frequently at thymine and
      guanine residues in DNA fragments obtained from the c-Ha-ras-1 protooncogene.
      When the p53 tumor suppressor gene was used, 4-nitro-2-aminophenol caused Cu(II)
      dependent piperidine-labile sites at poly G sequences. In the presence of Cu(II),
      both components increased 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in DNA.
      The inhibitory effects of catalase and bathocuproine on DNA damage suggest the
      involvement of H2O2 and Cu(I). It is speculated that nitro-2-aminophenols undergo
      Cu(II)-mediated autoxidation to generate active oxygen species causing DNA damage
      which leads to their carcinogenesis.

PMID- 9563651
TI  - Actin organization associated with the expression of multidrug resistant
      phenotype in osteosarcoma cells and the effect of actin depolymerization on drug
      resistance.
AB  - We have previously reported that P-glycoprotein (Pgp)-overexpressing multidrug
      resistant (MDR) osteosarcoma cells were functionally more differentiated than
      their parent cells. The present study showed that in the parent cells, the actin
      filaments were sparsely distributed or were diffusely spread throughout the
      cytoplasm, whereas the MDR osteosarcoma cells exhibited a remarkable increase in
      well-organized actin stress fibers. Furthermore, dihydrocytochalasin B, a
      specific inhibitor of actin polymerization, dramatically disrupted this network
      of stress fibers, increased the intracellular accumulation of doxorubicin (DOX)
      and modified the resistance against DOX. These results indicate that the
      organization of actin filaments associated with cellular differentiation may be
      involved in the expression of Pgp function in the MDR osteosarcoma cells.

PMID- 9563652
TI  - Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its
      mRNA in ovarian cancers.
AB  - The potential of growth, invasion and metastasis of ovarian cancer cells
      associated with neovascularization, and the expression of platelet-derived
      endothelial growth factor (PD-ECGF) and its mRNA in ovarian cancers were
      determined. The relationship between their expression and histopathological types
      and clinical stages of ovarian cancers was also analyzed. The levels of PD-ECGF
      and its mRNA were higher in ovarian cancers than in normal ovaries. Furthermore,
      some endometrioid carcinomas and serous cystadenocarcinomas of the ovary and some
      ovarian cancers in stages III and IV expressed remarkably high levels of PD-ECGF
      and its mRNA. Therefore, in some ovarian cancers, PD-ECGF might be related to
      advanced stages of ovarian cancers associated with neovascularization.

PMID- 9563653
TI  - Expression of multidrug resistance-associated protein (MRP) in head and neck
      squamous cell carcinoma.
AB  - We investigated the expression of multidrug resistance-associated protein (MRP)
      in 115 cases of head and neck squamous cell carcinoma (H&NSCC) by
      immunohistochemistry and examined the relationship between MRP expression and
      clinical factors. Thirty-four (30%) of 115 cases of H&NSCC had expression of MRP.
      The clinical stage was inversely associated with the expression of MRP (P =
      0.0090), but not with age, sex, tumor size, metastasis, recurrence, death from
      disease or overall survival rate for 5 years. In vitro chemosensitivity to five
      chemotherapeutic agents (cis-diamminedichloroplatinum, 5-fluorouracil,
      peplomycin, mitomycin C and Adriamycin) was tested by ATP assay and no
      correlation between the sensitivity of tumor cells to the cytotoxicity of any
      drug and MRP expression was found. These results suggest that the resistance to
      anticancer drugs is not dependent only on the expression of MRP in H&NSCC.

PMID- 9563654
TI  - Hypoxia-induced apoptosis in human hepatocellular carcinoma cells: a possible
      involvement of the 6-TG-sensitive protein kinase(s)-dependent signaling pathway.
AB  - Apoptosis is a morphologically and biochemically distinct form of cell death
      which can be triggered by a variety of extracellular agents both during normal
      developments and in adult pathological states. However, the molecular mechanism
      of apoptotic cell death due to hypoxia has not been clearly elucidated. In this
      study, we investigated critical factors involved in hypoxia-induced apoptosis
      using HepG2, a human hepatocellular carcinoma cell line, as an experimental
      model. We found that 24 h of exposure of HepG2 cells to hypoxia induced
      apoptosis, for which de novo protein synthesis was required. Apoptosis was
      demonstrated by DNA fragmentation and terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) assay. Hypoxia-induced apoptosis was
      associated with a marked induction of c-jun and c-fos messenger RNAs.
      Electromobility shift assay showed the increased DNA binding activity of AP-1
      during hypoxia, suggesting that AP-1 may be involved in the induction of cell
      death by acting as a transcriptional regulator. A purine analogue, 6-thioguanine
      (6-TG), significantly blocked the induction of apoptosis by hypoxia. Moreover,
      the inductive effect of hypoxia on c-jun expression was also inhibited by 6-TG,
      whereas the levels of c-fos mRNA and its protein were rather strongly increased.
      Iodoacetamide (IAA), a non-specific inhibitor of ICE family proteases, also has
      an inhibitory effect on hypoxia-induced apoptosis. These results suggest that the
      6-TG-sensitive protein kinase(s)-dependent signaling pathway may be involved in
      the apoptotic response of HepG2 cells exposed to hypoxia by increasing the level
      of c-jun and c-fos and the activity of AP-1 and/or by activating ICE family
      protease(s).

PMID- 9563655
TI  - Serum proteins with NAD+ glycohydrolase activity and anti-CD38 reactivity-
      elevated levels in serum of tumour patients.
AB  - NAD+ glycohydrolase activities in serum samples from cancer patients were two- to
      three-fold higher than the activities in samples from healthy controls. SDS-PAGE
      analysis of serum samples followed by Western blotting revealed the presence of
      two proteins of approximately 45 and approximately 21 kDa that were
      immunoreactive with human CD38-specific monoclonal antibodies T16, HIT2 and OKT
      10. These proteins appeared to be more abundant in serum from cancer patients.
      NAD+ glycohydrolase activity in serum could be enriched by immunoaffinity
      chromatography by using T16-Sepharose 4B. The results suggest that the relative
      abundance of proteins immunologically related to CD38 may account for the
      elevated levels of glycohydrolase activities in serum of tumour patients.

PMID- 9563656
TI  - Detection of tumor-derived DNA in exfoliated cells of urine sediments with a
      novel quantitative PCR method based on allele-specific PCR.
AB  - We have established a novel quantitative method based on the allele-specific PCR,
      which uses the linearly amplified fragment of the PCR products as the internal
      control. The improved characteristics of the procedure are the high sensitivity
      for quantitation of the mutant alleles at ratios of up to 1:10000 and the reduced
      necessity of the optimization of the PCR conditions for each mutation. Using this
      modified allele-specific PCR, we could quantify the tumor alleles in the urine
      sediments of three patients with urothelial cancers that harbored different p53
      gene mutations. This method can be applied to other genetic targets that have
      other types of alterations, such as deletions or insertions.

PMID- 9563657
TI  - 'Is there an evidence base for the practice of ENT surgery?'.

PMID- 9563658
TI  - Mitochondrial inherited hearing loss.

PMID- 9563659
TI  - Non-syndromic autosomal dominant sensorineural hearing loss: a new field of
      research.

PMID- 9563660
TI  - Hypernasality following adenoidectomy: a significant and avoidable complication.

PMID- 9563661
TI  - Acoustic rhinometry: an explanation of some common artefacts associated with
      nasal decongestion.
AB  - The nasal cavities of 51 healthy volunteers were examined using acoustic
      rhinometry before and after nasal decongestant. Several specific dimensions were
      studied, which included the minimum cross-sectional area, and three volumes
      corresponding to the anterior, middle and posterior regions of the nasal airway.
      An average acoustic rhinometry trace was constructed for the whole group of
      subjects, before and after decongestion, from data extracted from the raw data
      files written to the computer hard disk for each subject. A 27.5% (P < 0.0001)
      increase in the minimum cross-sectional area was observed, with no shift in its
      position. The greatest increase in nasal dimensions was seen in the anterior and
      middle parts of the nose, however, significant changes were also seen in the
      posterior nasal cavity and post nasal space. There are a number of possible
      sources of artefact. First, confusion of the first and second minima may produce
      apparent movement of the minimum cross-sectional area following nasal
      decongestion. Second, a postulated change in the acoustic path length may lead to
      apparent changes in volume in certain regions of the nose. Third, a variable and
      uncontrollable degree of sound energy loss will occur into the opposite nasal
      cavity beyond the posterior border of the septum. An apparent increase in the
      dimensions of this region will be seen as the opposite cavity decongests. We feel
      that all users of the acoustic rhinometer need to be aware of these potential
      sources of artefact, and attention needs to be focused on an agreed definition of
      the components of the acoustic rhinometry trace.

PMID- 9563662
TI  - Tumours of the minor salivary glands.
AB  - One hundred and forty-five patients were identified with minor salivary gland
      tumours. General information and tumour-specific information on stage, grade of
      tumour, resection margins, recurrence and survival were collected. Data was
      analysed by both univariate and multivariate methods. Indices predicting tumour
      recurrence and survival were analysed. Forty-two benign lesions, mostly
      pleomorphic adenomas were identified, one recurred, all survived. One hundred and
      three malignant lesions were identified, mostly adenoid cystic carcinomas (70%)
      or mucoepidermoid carcinomas (19%). Late stage disease and the presence of neck
      node metastases predicted both early recurrence and high eventual mortality.
      Survival was favoured by the histological type (mucoepidermoid > adenoid cystic),
      site of primary (oral cavity and oropharynx > nose, sinuses and larynx) and good
      general condition. Many tumours recurred after 5 years of disease-free survival
      and late mortality was a feature (80% survival at 5 years, 20% at 20 years). Many
      patients survive some time with either local recurrence or distant metastases.
      Long-term follow-up is advocated as local or distant recurrence may be treatable.
      The value of super radical treatment of the primary is questionable given the
      likelihood of recurrence at distant sites.

PMID- 9563663
TI  - The current role of local intratympanic gentamicin therapy in the management of
      unilateral Meniere's disease.
AB  - Over the past 5 years 25 patients suffering from disabling unilateral Meniere's
      disease have been treated in our unit with local intratympanic Gentamicin therapy
      with the specific intent of creating a medical labyrinthectomy, together with
      preservation of hearing on the treated side. Results from the 16 patients who
      have completed a 2-year follow-up show that substantial control of vertigo was
      obtained in all subjects, while 87% experienced complete control of vertigo
      following treatment. In 66% this was achieved in association with a complete
      medical labyrinthectomy (no caloric response to an iced water stimulus). In 94%
      of patients the hearing on the treated side has remained unaffected, but tinnitus
      was largely unchanged. The simple treatment protocol uses a customized self
      retaining intratympanic catheter system (courtesy of Exmoor Plastics Ltd). The
      findings suggest that local Gentamicin therapy is an effective treatment in
      patients with incapacitating unilateral Meniere's disease and is associated with
      low morbidity and good hearing preservation and thus provides a potentially
      superior alternative to the surgical treatment options currently available.

PMID- 9563664
TI  - Changes in the vestibulo-ocular reflex: a study of elderly day hospital patients.
AB  - The vestibulo-ocular reflex (VOR) of 50 elderly day hospital patients (mean age
      of 82 years) was studied with the head autorotation test. Amplitude gain, phase
      and the highest frequency band reached were determined in the five frequency
      bands of 1, 2, 3, 4, and 5 Hz. Of the 50 patients, 81% had abnormal results. The
      gain of the elderly was significantly increased to 1.06-1.24 in the frequency
      bands of 3, 4, and 5 Hz in comparison with that of a control group. The elderly
      showed constantly a phase lead of 8-19 degrees in the frequency range of 1-4 hz
      and in this range differed significantly from the control group. The percentage
      of the elderly who reached high frequencies of head movements was reduced to 55%
      in the frequency band of 3 Hz and to 30% in the frequency band of 4 Hz. These
      findings may lead to oscillopsia and explain the high prevalence of dizziness and
      falls among the elderly.

PMID- 9563665
TI  - Predictors of outcome in children with otitis media with effusion.
AB  - Otitis media with effusion (OME) is the commonest cause of hearing impairment in
      young children. The fluctuating nature of the condition makes identification of
      those with persistent disease difficult without subjecting each child to a period
      of 'watchful waiting'. The aim of this study was to determine if the outcome of
      this observation period could in any way be predicted. The study involved the
      retrospective analysis of 517 children, aged 3-15 years (mean 5 years and 4
      months) in whom the diagnosis of OME had been established. All children had been
      subjected to an observation period before a decision on surgery was taken. There
      was a significant correlation between the degree of hearing loss at presentation
      and after the period of observation. Sex was not a reliable predictor of outcome,
      but age less than 4 years and presentation in autumn or winter were associated
      with a poor audiometric outcome. This study identifies a predictive influence on
      the resolution of OME for these three factors and points the way for future
      research aimed at identifying the subgroup of children with OME who would benefit
      from early surgical intervention.

PMID- 9563666
TI  - The effects of age on survival and other parameters in squamous cell carcinoma of
      the oral cavity, pharynx and larynx.
AB  - Many papers have been written on the effect of age on survival from cancer and a
      number of these papers have concentrated on cancer of the head and neck. The
      literature is fairly evenly split between those studies that claim that the young
      patient has a better chance of survival and those that suggest the older patient
      has a better chance of survival. The present study investigates 2647 patients
      with histologically proven squamous cell carcinoma of the oral cavity,
      oropharynx, larynx and hypopharynx. The tumour-specific 5-year survival of
      patients with head and neck cancer from the third decade through to the seventh
      decade at presentation was 54%, whereas this figure dropped to 44% for the
      eighth, ninth and tenth decades. This difference was statistically significant (P
      = 0.0001). When the patients in the third to seventh decades of presentation were
      compared with those from the eighth to tenth decades, it was found that older
      patients tended to have significantly more advanced disease at the primary site
      and fewer neck node metastases when compared with younger patients at
      presentation. These differences were confirmed by multiple logistic regression.
      Multivariate analysis of survival confirmed that advanced age was associated with
      poor survival (P = 0.0001). Whilst patients with head and neck cancer in their
      eighth, ninth and tenth decades fared worse than younger patients, their mean
      tumour specific survival at 5 years was in the region of 44%, which makes
      treatment worthwhile, certainly in selected cases.

PMID- 9563667
TI  - p53 protein expression in tumours from head and neck subsites, larynx and
      hypopharynx, and differences in relationship to survival.
AB  - The present study involves an immunohistochemical analysis of p53 protein
      expression in head and neck tumours located at two separate subsites, the larynx
      and hypopharynx. It attempts to relate differences in expression to differences
      in the behaviour of these tumours. Detection of the p53 protein was performed
      using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell
      carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53
      overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the
      laryngeal specimens analysed. Some differences between the two tumour types were
      noted in the pattern staining. p53 staining in those with hypopharyngeal tumours
      was associated with a statistically significant increased survival. For laryngeal
      carcinoma the converse was true but did not reach statistical significance.
      Differences in the behaviour of different head and neck tumour types may be
      reflected in differences in expression of the p53 protein. While p53 protein
      expression does not appear to be a useful prognostic indicator in laryngeal
      carcinoma it might be a useful prognostic indicator in tumours of the
      hypopharynx. Moreover, it may help predict those tumours which are
      radioresistant, thus suggesting other modes of treatment for these tumours. Of
      particular importance is the molecular basis for the observed differences in
      survival associated with p53 expression in the two tumour sites. This is under
      further investigation.

PMID- 9563668
TI  - Bacteraemia during tonsillectomy: a study of the factors involved and clinical
      implications.
AB  - Post-tonsillectomy bacteremia is a well-recognized aetiological factor in
      streptococcal endocarditis, and prophylactic penicillin has been recommended to
      reduce its incidence in susceptible patients undergoing tonsillectomy. Recent
      studies have shown a change in the microflora and an increase in the number of
      penicillin-resistant organisms in the tonsils of patients undergoing
      tonsillectomy. The aim of this study was to assess the incidence of post
      tonsillectomy bacteraemia, to identify the micro-organisms associated with it and
      to review the suitability of penicillin in prophylactic regimens. The
      relationship between positive blood cultures and several clinical parameters such
      as fever, vomiting, pharyngeal discomfort, or dysphagia was also analysed. Of the
      102 patients included in the study, 41 (40.1%) had positive post-tonsillectomy
      blood cultures. Haemophilus influenzae were isolated from 23 (56%) of the
      positive cultures and Streptococcus viridans in 15 (36.5%). Twenty-five per cent
      of H. influenzae produced beta-lactamase and only 30% of streptococci of the
      viridans group were penicillin-sensitive. Positivity of the blood cultures was
      not related to fever, discomfort, surgical technique, type of tonsil, or any of
      the parameters studied. Bacteraemia seems to be related to traction of the tonsil
      before dissection rather than direct spread of bacteria into the opened vessels.
      Using a beta-lactamase stable antibiotic instead of penicillin for prophylaxis
      would be more appropriate.

PMID- 9563669
TI  - Tonsillitis and chronic psoriasis.
AB  - Although the relationship between streptococcal tonsillitis and acute guttate
      psoriasis is well recognized, its relationship to chronic forms of psoriasis is
      less established. In order to explore this further, the authors questioned 35
      patients with severe psoriasis and 35 age-matched eczema controls about their
      history of significant sore throats (i.e. requiring a GP visit) and any resultant
      worsening of the skin condition. A third of the psoriasis patients reported
      recurrent sore throats which worsened their skin condition. This was true of only
      one (3%) of the 35 eczema controls. The authors discuss these findings in the
      context of recent laboratory work on the association between streptococcal
      infection and psoriasis.

PMID- 9563670
TI  - A 1-year placebo-controlled study of intranasal fluticasone propionate aqueous
      nasal spray in patients with perennial allergic rhinitis: a safety and biopsy
      study.
AB  - In a 1-year, placebo-controlled, double-blind, randomized study the long-term
      effect of Fluticasone Propionate Aqueous Nasal Spray (FPANS) in 42 patients with
      a perennial allergic rhinitis was studied with regard to safety and efficacy.
      Twenty-nine patients completed the entire treatment period. After 1 year of
      treatment no deleterious changes consequent on therapy were observed in nasal
      mucosal biopsies. The appearance of the epithelial layer, the degree of cellular
      infiltration, the extent to which the sinusoids were dilated and the degree of
      tissue oedema improved or remained unchanged in 93% of the patients of the FPANS
      group, versus 75% of the placebo group, and worsened in 7% of the FPANS group
      versus 25% of the placebo group. Assessment of the changes in haematological,
      biochemical, urinary, plasma cortisol levels, and in the findings during nasal
      examination revealed no significant differences between the two treatment groups.
      After 1 year of treatment symptom scores for sneezing, nasal itching, and total
      symptom score were significantly better in the FPANS treated group (P < 0.05, P <
      0.05, P < 0.01). An initial reduction in total symptom score was found after 4
      weeks FPANS treatment with a further reduction after 8 months of FPANS treatment.
      These findings suggest that the maximum efficacy of topical intranasal steroids
      is reached after long-term treatment, and thus advocates longer usage before
      treatment is stopped because of presumed inefficacy.

PMID- 9563671
TI  - The value of sedation nasendoscopy: a comparison between snoring and non-snoring
      patients.
AB  - Sedation or sleep nasendoscopy is a widely-used investigation in snorers
      presenting to otolaryngologists in the UK, despite its non-physiological basis.
      The presence or absence of snoring and its site of generation were compared
      between a group of 205 snorers and another of 126 non-snorers. Snoring was
      produced at nasendoscopy in 45.3% of non-snorers but could not be produced in
      18.1% of snorers. There was no significant difference in the site of sound
      production between the two groups and although the noise produced by the non
      snoring group was quieter, this difference was not significant.

PMID- 9563672
TI  - Target oriented computed tomography-scanning of the paranasal sinuses.
AB  - A limited computed tomography (CT) scanning protocol for the paranasal sinuses is
      proposed consisting of only seven cuts in the coronal plane. A retrospective
      observational study has shown the ability of these cuts to demonstrate the
      regions of interest to the FESS surgeon. The regions are detected at a rate
      ranging from 85% to 96% in this sample of 100 patients. The novelty of the
      protocol is the principle of targeting those regions. We believe that the
      targeted protocol is practically feasible and provides the necessary information
      concerning benign sinus disease, along with the expected reduction of exposure to
      radiation and reduction of cost.

PMID- 9563673
TI  - A study of a new tumour marker, CYFRA 21-1, in squamous cell carcinoma of the
      head and neck, and comparison with squamous cell carcinoma antigen.
AB  - CYFRA 21-1 (CYFRA) is a newly developed tumour marker which is useful in
      evaluating large cell lung carcinoma, especially the squamous cell type. The
      purpose of this study was to assess the clinical value of CYFRA for squamous cell
      carcinoma of the head and neck and compare the results with squamous cell
      carcinoma antigen (SCCA). Serum levels of CYFRA were measured in 168 patients
      with a newly diagnosed head and neck squamous carcinoma. In addition, 77 patients
      without evidence of neoplasm were included as controls. At the same time, SCCA
      was also determined. The cut-off values of CYFRA and SCCA, determined at the 95th
      percentile of the standard Gaussian variate of controls, were 2.48 ng/ml and 1.49
      ng/ml respectively. The diagnostic sensitivity of CYFRA was superior to that of
      SCCA, especially for nasopharyngeal carcinoma. The sensitivity of CYFRA for
      nasopharyngeal carcinoma was much higher (58.3%) than that of SCCA (15.5%).
      However, the sensitivity of CYFRA is not satisfactory in all types of squamous
      carcinoma. For oral cancer, the sensitivity is only 25.6%. CYFRA is a useful
      serum marker for patients with certain types of head and neck squamous carcinoma,
      such as nasopharyngeal carcinoma and hypopharyngeal carcinoma. In addition, CYFRA
      may be also useful in monitoring recurrence of certain types of SCCHN, which are
      sometimes difficult to detect.

PMID- 9563674
TI  - Transient otoacoustic emissions in children with chronic renal failure.
AB  - This study was conducted on 34 children with chronic renal failure: 27 on regular
      haemodialysis and seven on conservative treatment. Twenty normal healthy children
      served as controls. They were subjected to clinical examination including
      otoscopic examination, basic audiological assessment and transient otoacoustic
      emission testing (TOAE). Four patients had a conductive hearing loss and five had
      a bilateral moderately severe high frequency sensory neural hearing loss. TOAE
      testing was carried out for the rest whose ears displayed normal hearing. No
      response (fail) was obtained in 8% of them but in none of the controls and a
      partial pass response in 38% versus 10% of controls (P < 0.001). Cochlear
      dysfunction was significant only at low frequency levels. The mean overall echo
      level and reproducibility were significantly lower in patients than in controls.
      The same holds true for the subgroup of patients on haemodialysis but not for
      those on conservative treatment. The overall echo-levels did not correlate with
      serum urea, creatinine, sodium or potassium.

PMID- 9563675
TI  - Direct listing' for tonsillectomy by general practitioners.
AB  - The aim of this prospective study was to determine the suitability of 'direct
      listing' of patients for tonsillectomy by their General Practitioner. All General
      Practitioners were issued guidelines outlining the indications and
      contraindications for direct listing. One hundred consecutive patients, referred
      over a 6-month period, were screened by an otolaryngologist. Thirty-three of
      these patients were referred inappropriately. The high rate of inappropriate
      referrals would suggest that this is an unacceptable practice.

PMID- 9563676
TI  - Permanent mastoid vent: a new treatment for persistent eustachian tube
      obstruction.
AB  - To date, there is no satisfactory treatment for persistent eustachian tube
      blockage or negative pressure in the middle ear. Conventional ventilation tubes
      are usually either occluded or extruded with time. A new treatment of
      percutaneous mastoid vent provides permanent ventilation to the middle ear cleft
      without putting a tube through the eardrum. A titanium tube is inserted through
      the skin into the mastoid antrum using the established technique of osseo
      integration and hence becomes truly permanent. It can also be connected to a CPAP
      machine to re-inflate a collapsed eardrum. Initial trials consist of six vents
      inserted and followed up for 6-16 months. There was no sign of extrusion or a
      foreign body reaction. However, an inner Teflon tube is essential to keep the
      vent patent for permanent ventilation to the middle ear cleft.

PMID- 9563677
TI  - Transcription and DNA replication of sperm nuclei introduced into blastomeres of
      2-cell mouse embryos.
AB  - The aim of this study was to investigate the behaviour of sperm nuclei in the
      cytoplasm of the 2-cell mouse embryo. To this end, we produced hybrids between
      anucleate fertilised oocyte fragments and blastomeres of the 2-cell embryos. When
      sperm nuclei at the stage of decondensation or recondensation were introduced
      into blastomeres the development of male pronuclei was usually retarded and they
      never reached the size of the blastomere nuclei. These abortive male pronuclei
      were unable to initiate transcription but they were capable of synthesising DNA.
      The majority of sperm nuclei introduced into blastomeres as early male pronuclei
      developed normally and reached the size of the blastomere nuclei. They
      synthesised DNA simultaneously with blastomere nuclei and were transcriptionally
      active. In addition they participated in the cleavage division of hybrid cells.
      This shows that the very early male pronucleus when transmitted from the oocyte
      cytoplasm to the blastomere cytoplasm can respond positively to the new
      cytoplasmic factors, i.e. it undertakes both DNA replication and transcription
      according to the time schedule characteristic of the second cell cycle.

PMID- 9563678
TI  - Fate of microinjected sperm components in the mouse oocyte and embryo.
AB  - Intact mouse sperm or mouse sperm tails alone, labelled with MitoTracker Green FM
      fluorochrome, were injected into mouse oocytes and the cells cultured in vitro
      for up to 5 days. The dye stained midpiece mitochondria, the sperm tail coarse
      fibres and the sperm perforatorium. Intact sperm (or tails injected with
      separated heads) induced normal embryonic development. The mitochondria could be
      identified in embryos up to the 4-cell stage, remaining associated with the sperm
      tail. They largely disappeared by the 8-cell stage, when only a minority of
      embryos (6/43) could be found with small patches of mitochondria. Axonemal
      elements could be identified coiled up in single external blastomeres as late as
      day 5 blastocysts. By contrast, mitochondria as well as tail components could be
      identified up to 5 days after injection of sperm tails alone into non-activated
      oocytes and also in embryos that arrested development before the 8-cell stage. We
      conclude that disappearance of the labelled sperm mitochondria in normally
      cleaving embryos is not due to fading or inactivation of the fluorochrome marker,
      but is rather an event specifically tied to cell cycle activities around the
      second cell division.

PMID- 9563679
TI  - Use of a chemically defined system for the direct comparison of inner cell mass
      and trophectoderm distribution in murine, porcine and bovine embryos.
AB  - The mammalian blastocyst comprises an inner cell mass (ICM) and a trophectoderm
      cell layer. In this study the allocation of blastomeres to either cell lineage
      was compared between murine, porcine and bovine blastocysts. Chemical permeation
      of trophectoderm cells by the Ca2+ ionophore A23187 in combination with DNA
      specific fluorochromes resulted in the differential staining of trophectoderm and
      ICM. Confocal microscopy confirmed the exclusive permeation of trophectoderm and
      the internal localisation of intact ICM cells in bovine blastocysts. Overall,
      differential cell counts were obtained in approximately 85% of the embryos
      assessed. Mean (+/-SEM) total cell numbers were 72.2+/-3.1 and 93.1+/-5 for in
      vivo derived murine (n = 41) and porcine (n = 21) expanded blastocysts,
      respectively. Corresponding ICM cell number counts revealed ICM/total cell number
      ratios of 0.27 and 0.21, respectively. Comparison of in vivo (n = 20) and in
      vitro derived bovine embryos on day 8 (n = 29) or day 9 (n = 29) revealed a total
      cell number of 195.25+/-9.9, 166.14+/-9.9 and 105+/-6.7 at the expanded
      blastocyst stage with corresponding ICM/total cell ratios of 0.27, 0.23 and 0.23,
      respectively. While total cell numbers differed significantly among the three
      groups of bovine embryos (p < 0.05), the ICM/total cell ratio did not. These
      results indicate that a similar proportion of cells is allocated to the ICM among
      blastocysts of genetically divergent species.

PMID- 9563680
TI  - Expression of Fas-Fas ligand system associated with atresia in murine ovary.
AB  - We detected that Fas receptor (Fas) was expressed at transcriptional levels in
      oocytes/eggs and some granulosa cells of murine ovary, whereas, Fas ligand (FasL)
      was found to be strongly expressed in granulosa cells by means of in situ
      hybridisation. These results were supported by an indirect immunofluorescence
      (IIF) test with anti-Fas monoclonal antibody (mAb)/FasL Ab. The lysates from
      granulosa cells were precipitated by anti-FasL Ab, exhibiting a specific band at
      40 kDa. When zona pellucida (ZP)-free eggs were incubated with granulosa cells in
      vitro, apoptosis (DNA fragmentation) was induced in the eggs, as detected by the
      terminal deoxynucleotide transferase mediated dUTP-nick end labelling (TUNEL)
      method. To examine whether FasL-bearing cells can induce apoptosis in eggs
      expressing Fas through molecular interaction between FasL and Fas, we employed a
      baculovirus expression system to generate FasL on the surface of Spodoptera
      frugiperda (Sf9) cells. The co-incubation of eggs with Autographa californica
      nuclear polyhedrosis virus (AcNPV) and FasL transfected Sf9 (Sf9-FasL) cells in
      vitro was performed and resulted in the induction of apoptosis in eggs as
      detected by the TUNEL method. Apoptosis was absent in eggs co-incubated with
      AcNPV-1393 transfected Sf9 (Sf9-1393) cells. Thus, ovarian atresia was suggested
      to be induced by molecular interaction between FasL on granulosa cells and Fas on
      oocytes/eggs during oogenesis.

PMID- 9563681
TI  - Activation of the metaphase checkpoint and an apoptosis programme in the early
      zebrafish embryo, by treatment with the spindle-destabilising agent nocodazole.
AB  - We have studied the developmental activation of the metaphase checkpoint, and the
      consequences of activating this checkpoint, in the zebrafish embryo. (1)
      Treatment with nocodazole (a microtubule destabiliser) before mid-blastula
      transition (MBT) produces complete destruction of all nuclei in the deep cell
      layer of the embryo. In contrast, nocodazole treatment after MBT efficiently
      produces metaphase arrest in this cell layer. Thus, the metaphase checkpoint
      becomes activated at MBT. (2) Although a metaphase arrest is induced by
      nocodazole, it is not induced by paclitaxel (a microtubule stabiliser). Thus the
      metaphase checkpoint appears to sense a destabilisation, but not a stabilisation,
      of spindle microtubules. (3) Metaphase-arrested cells (in nocodazole) can be
      driven into the next interphase by adding the Ca2+-specific ionophore A23187.
      Thus, a Ca2+-signalling pathway lies downstream of, or parallel to, the metaphase
      checkpoint. (4) After mid-gastrula stage, treatment with nocodazole produces DNA
      fragmentation in all three cell layers. In the enveloping epithelial monolayer
      (EVL), this is associated with a classical apoptotic phenotype. In the deep
      layer, it is associated with an unusual, highly condensed nuclear state that is
      entered directly from metaphase arrest. Thus, after the mid-gastrula stage, the
      embryo responds to nocodazle by undergoing apoptosis. (5) Nocodazole-induced
      apoptosis in the deep cell layer can be blocked by the caspase-1,4,5 inhibitors
      Ac-YVAD-CHO and Ac-YVAD-CMK. This suggests that a homologue of the C. elegans ced
      9-ced-4-ced-3 pathway is involved in control over apoptosis in the early
      zebrafish embryo.

PMID- 9563682
TI  - Laser blastocyst biopsy for preimplantation diagnosis in the human.
AB  - A new methodology for blastocyst biopsy that uses a 1.48 microm diode laser is
      described. Trophectoderm cells are biopsied after laster zona drilling and
      culture, fixed and processed for fluorescent in situ hybridisation (FISH)
      analysis. Preliminary results on the efficiency of the procedure and blastocyst
      recovery rate are promising. Blastocyst laser biopsy is a useful tool in
      preimplantation genetic diagnosis (PGD) as it allows a more reliable diagnosis
      and widens the diagnostic possibilities on account of the higher number of cells
      obtained in the biopsy.

PMID- 9563683
TI  - Inositol triphosphate receptors in sea urchin sperm.
AB  - Inositol 1,4,5-triphosphate (Ins(1,4,5)P3) is a second messenger that regulates
      Ca2+ channels in many important cell signalling pathways. In sea urchin sperm the
      outer investment of the egg triggers the acrosome reaction (AR) that involves
      Ins(1,4,5)P3 production and the opening of two Ca2+ channels. Here we have sought
      to identify a high-affinity Ins(1,4,5)P3 receptor in Strongylocentrotus
      purpuratus sperm. An Ins(1,4,5)P3 binding component was affinity-purified 12-fold
      from sperm extracts. It displayed similar characteristics to the Ins(1,4,5)P3
      receptor from other sources: pH-dependent high affinity for Ins(1,4,5)P3 (KD =
      261 nM), a tau1/2 of association and dissociation of 50 and 40 s, respectively,
      specificity (IC50 > 5 microM for Ins(1)P1, Ins(1,4)P2 and Ins(1,3,4,5)P4), and
      pharmacological sensitivity (10 and 100 microg heparin/ml inhibited 75% and 100%
      binding respectively). An antibody against the carboxy-terminal of the type I
      Ins(1,4,5)P3 receptor of somatic cells recognised a plasma membrane component in
      the sperm head and less intensely in the flagella. This antibody also recognised
      a 240 kDa band from isolated head plasma membranes, and weakly in flagellar
      membrane. This IP3 receptor-like protein may mediate the sustained uptake of Ca2+
      through the second Ca2+ channel opened during the AR.

PMID- 9563684
TI  - Blastocoele formation and cell allocation to the inner cell mass and
      trophectoderm in haploid and diploid pig parthenotes developing in vitro.
AB  - The objective of this study was to determine developmental pattern and cell
      allocation to the inner cell mass and trophectoderm in haploid and diploid
      embryos following parthenogenetic activation. In vitro matured porcine oocytes
      were activated by ethanol treatment and cultured in the presence or absence of
      cytochalasin B for 5 h. The oocytes were then cultured in the NCSU23 for 9 days.
      The combined treatment with cytochalasin B following ethanol treatment did not
      increase (p > 0.1) the incidence of activation. The incidence of development to
      the blastocyst stage was higher (p < 0.05) in the combined treatments of ethanol
      and cytochalasin B as compared with ethanol treatment alone. The percentage of
      oocytes with two female pronuclei was higher (p < 0.01) in oocytes treated with
      cytochalasin B than that in ethanol treatment alone. Treatment with both ethanol
      and cytochalasin B increased (p < 0.01) the incidence of diploid chromosome
      spread over just the ethanol treatment alone. The average numbers of total cells
      and inner cell mass were significantly reduced (p < 0.05) in the ethanol
      treatment alone as compared with the combined cytochalasin B and ethanol
      treatment. These results suggested that the ploidy may affect blastocoele
      formation and cell allocation to inner cell mass and trophectoderm in the pig.

PMID- 9563685
TI  - Distribution of cortical granules in bovine oocytes classified by cumulus
      complex.
AB  - The present study was conducted to examine distributional changes of cortical
      granules (CGs) during meiotic maturation and fertilisation in vitro and the
      developmental ability in bovine oocytes classified by cumulus cells. The oocytes
      were classified by the morphology of their cumulus cell layers as follows: class
      A, compact and thick; class B, compact but thin; class C, naked; and class D,
      expanded. Some of the oocytes were stained with Lens curinalis agglutinin (LCA)
      before and after maturation in vitro and after insemination, and then stained
      with orcein to observe their nuclear stages. The others were left in culture.
      Distributional patterns of the CGs were classified into four types: type I, CGs
      distributed in clusters; type II, CGs dispersed and partly clustered; type III,
      all CGs dispersed; and type IV, no CGs. Most of the oocytes before culture showed
      a type I pattern, but this decreased after maturation culture, whereas type III
      increased in class A. The oocytes of class B showed similar changes while the
      oocytes of class C did not. In class C, many oocytes showed type I after culture,
      indicating that cytoplasmic maturation was not completed. In class D, 80.4% of
      the oocytes exhibited type III before maturation culture, indicating that their
      cytoplasmic maturation was different from classes A-C. And about 70% of the class
      D oocytes were at the nuclear stage of germinal vesicle breakdown (GVBD) before
      culture. The developmental rates to blastocysts in classes A-D were 28.7%, 23.1%,
      0.5% and 3.4% respectively.

PMID- 9563686
TI  - Review of epidemiological studies on health effects from exposure to recreational
      water.
AB  - BACKGROUND: In order to facilitate the setting of guidelines, this review article
      evaluates the health risks caused by poor microbiological quality of recreational
      natural water. METHODS: Studies on uncontrolled waters, such as sea, lakes and
      rivers were considered in this review through MEDLINE and WHO resources. Out of
      the 37 studies identified, 22 were reviewed because they addressed associations
      of interest and fulfilled the validity criteria. RESULTS: Most studies reported a
      dose-related increase of health risk in swimmers with an increase in the
      indicator-bacteria count in recreational waters. Relative risk (RR) values for
      swimming in polluted water versus clean water were often significant (usually 1.0
      < RR < 3.0). The indicator microorganisms that correlate best with health
      outcomes were enterococci/faecal streptococci for both marine and freshwater, and
      Escherichia coli for freshwater. In both marine and freshwater, increased risk of
      gastro-intestinal symptoms was reported for water quality values ranging from
      only a few indicator counts/100 ml to about 30 indicator counts/100 ml. These
      values are low compared with the water qualities frequently encountered in
      coastal recreational waters. Studies which showed a higher threshold for
      increased risk and case-rate values in some countries may suggest immunity due to
      endemicity or a lower pathogen-to-indicator ratio in the natural waters.
      CONCLUSIONS: The review strongly suggests a causal dose-related relationship
      between gastrointestinal symptoms and recreational water quality measured by
      bacterial indicator counts.

PMID- 9563687
TI  - Cancer incidence, morbidity and geothermal air pollution in Rotorua, New Zealand.
AB  - BACKGROUND: The New Zealand city of Rotorua sits on a geothermal field. However,
      little is known about the possible health impacts of the geothermal emissions.
      This was an ecological study that examined cancer incidence and morbidity data
      for Rotorua. METHODS: Cancer registry and hospital discharge (morbidity) data
      were obtained for the decade 1981-1990. Standardized incidence ratios (SIR) were
      calculated comparing Rotorua residents with those living in the rest of New
      Zealand. Diagnostic categories examined were based on known target organ systems
      of hydrogen sulphide toxicity. RESULTS: Of the cancer sites, there was an
      elevated rate for nasal cancers. However, this was based on only four cases. The
      SIR for cancers of the trachea, bronchus and lung in Maori women was 1.48 (95%
      CI: 1.03-2.06). This was not explained by higher smoking rates. In the hospital
      discharge data, a number of diseases showed elevated SIR, notably diseases of the
      nervous system and the eye. To some extent, these effects were characteristic of
      effects induced by hydrogen sulphide and also mercury compounds. However, there
      were few data with which to assess whether significant mercury exposures had
      occurred, and other explanations were possible. CONCLUSIONS: There are inadequate
      exposure data for Rotorua to permit conclusions on likely causal associations.
      However, some of the elevated disease rates were at least consistent with what
      one might expect to find if sufficient exposures to hydrogen sulphide and/or
      mercury were occurring.

PMID- 9563688
TI  - Trends in cerebrovascular disease mortality in Singapore: 1970-1994.
AB  - BACKGROUND: Cerebrovascular disease has been the third leading cause of death in
      Singapore for the last 25 years. This study was carried out to examine recent
      trends in cerebrovascular disease mortality in Singapore, and to study
      corresponding changes in stroke risk factors in our population. METHODS: The
      Registry of Births and Deaths, Singapore, publishes annual reports on births and
      deaths. The cause of death is coded using the International Classification of
      Diseases Revisions 8 (1969-1978) and 9 (1979 onwards). Data for this study were
      obtained using rubrics 430-438. Death rates were age- and sex-standardized to the
      World Standard Population, and separately for males and females. Cerebrovascular
      disease risk factor patterns were derived from national epidemiological health
      surveys conducted from 1970 and 1994. RESULTS: The absolute number of deaths
      annually from cerebrovascular disease rose from 1041 in 1970 to 1692 in 1994.
      Crude death rates remained stable at 50-60 per 100000, accounting for 10-12% of
      all deaths. Standardized death rates showed a distinct fall from 99 per 100000 in
      1976 to 59 per 100000 in 1994, 101 to 60 per 100000 in males and 95 to 57 per
      100000 in females. National health surveys have shown a fall in the prevalence of
      undetected hypertension, smoking and hyperlipidaemia; the prevalence of obesity
      was unchanged, while that of diabetes mellitus rose over the same period. The
      mortality trends found in this study are unlikely to be due to changing fashions
      in coding or inadequate data collection. CONCLUSION: As in many countries in the
      world, cerebrovascular disease mortality in Singapore has fallen over the last 25
      years; this may in part be related to the decline in stroke risk factors in our
      population.

PMID- 9563689
TI  - The decline of smoking among Swedish men.
AB  - BACKGROUND: In 1987 the Association of the Nordic Cancer Registers (ANCR)
      predicted the incidence of lung cancer in the Nordic countries up to the years
      2000 and 2010. The predictions for Sweden can now be considered against recent
      information on smoking habits. METHODS: Regular, question-based studies on the
      public's tobacco consumption are carried out by four separate institutions in
      Sweden. This article summarizes and updates the smoking habits among Swedish men
      in the age groups 35-54 and 55-70 years between 1963 and 1994, with special focus
      on smoking cessation. RESULTS: Between 1963 and 1994, there was a significant and
      continuous decrease in the prevalence of smoking among Swedish men. During this
      time ex-smoking men increased from 20% to 41%. The data reveal a continuous,
      unbroken and uniform increase in smoking cessation rates during the last 20
      years, despite the small success of smoking cessation programmes and smoking
      relapse rates of 75-80%. The explanation of this seems to be the surprisingly
      high frequency of smokers who attempted to stop smoking each year (about 30%).
      The best success rate in smoking cessation was achieved by occasional smokers and
      others with a low cigarette consumption. CONCLUSION: With the continuing fall in
      the numbers of smoking men, a greater drop in lung cancer incidence than
      predicted by the ANCR in 1987 may be expected in Sweden within the coming decade.

PMID- 9563690
TI  - Mortality in women and men in relation to smoking.
AB  - BACKGROUND: Mortality from smoking-related diseases in women is increasing
      worldwide. Studies comparing hazards associated with smoking in women and men
      based on a sufficient number of heavy smokers of both genders are lacking.
      METHODS: We used pooled data from three prospective population studies conducted
      in Copenhagen to compare total and cause-specific mortality in relation to
      smoking habits. A total of 30917 subjects, 44% women, with initial examinations
      between 1964 and 1992 were followed until 1994 for date and cause of death.
      RESULTS: During follow up, 2900 women and 5744 men died. Smoking characteristics
      differed considerably with gender, particularly in the older subjects. Overall
      mortality rates in smokers were approximately twice those in people who never
      smoked. Positive associations with smoking in both men and women were confirmed
      for all-cause mortality as well as mortality from respiratory disease, vascular
      disease, lung cancer, and other tobacco-related cancers. Despite large gender
      differences in age at smoking debut, total and cause-specific relative mortality
      in smokers was similar in men and women. After excluding non-inhalers, relative
      risks associated with smoking for respiratory and vascular disease were higher
      for women than men whereas there were no gender differences in smoking related
      risk of cancers. CONCLUSIONS: The relative risks suggest that women may be more
      sensitive than men to some of the deleterious effects of smoking. However,
      because of lower baseline mortality rates in women, rate differences may be
      similar and results should be interpreted with caution.

PMID- 9563691
TI  - The impact of individual and area characteristics on urban socioeconomic
      differences in health and smoking.
AB  - BACKGROUND: In general, poor health and lifestyles occur more frequently among
      individuals of low socioeconomic status (SES) and in deprived areas. An
      explanation for the latter may simply be the on average lower SES of residents of
      these areas. It is possible, however, that living in a deprived area contributes
      to poor health and lifestyles. This study examines whether such an area
      contribution exists in urban settings. METHODS: Data on health, smoking, and
      individual SES were collected on 5121 residents of Amsterdam, the Netherlands, by
      face-to-face interviews (response: 61.4%). Area deprivation was measured by
      indicators used previously, on 22 areas. Odds ratios (OR) for poor health (poor
      self-rated health, long-term limitations, health complaints and obesity) and
      smoking were computed comparing tertiles of area deprivation. All analyses
      employed multilevel techniques, with residents hierarchically nested within
      areas. RESULTS: The age- and gender-adjusted prevalences of poor health and
      smoking are higher in deprived urban areas. Most of the differences in poor
      health can be explained by the on average lower SES of residents of deprived
      areas. Only for long-term limitations and obesity, some statistically significant
      area-differences remain. The higher prevalence of smoking in deprived areas can
      only partially be explained by the SES of residents. CONCLUSIONS: Adverse health
      status in deprived areas is mainly due to a lower individual SES and not to
      contextual factors. For smoking, living in a deprived area contributes to a
      higher prevalence. This shows the necessity of community-based preventive
      interventions in deprived areas.

PMID- 9563692
TI  - Respiratory symptoms due to active and passive smoking in junior secondary school
      students in Hong Kong.
AB  - BACKGROUND: Evidence on respiratory symptoms due to smoking and passive smoking
      in children is mainly derived from studies in Western countries. Evidence from
      the East was required to support stronger tobacco control policy in Asia. This
      study aimed to analyse the relationship between respiratory symptoms and smoking
      status in junior secondary students and between respiratory symptoms and family
      smoking in never-smoking students. METHODS: In a cross-sectional survey in 1994,
      anonymous questionnaires were administered to a two-stage cluster probability
      sample of 6304 students, aged mostly 12-15 years, from 172 classes of 61 schools
      in Hong Kong. RESULTS: Significant linear trends were found between smoking and
      the prevalence of throat and nose problems, cough and phlegm, and wheezing. The
      odds ratio (OR), after adjustment for age, gender, area of residence, type of
      housing and correlation within schools and classes (cluster effects), for smoking
      at least weekly ranged from 1.35 to 4.84. In never-smoking children, significant
      trends were found between the number of smokers living with the children and
      throat and nose problems, cough and phlegm, and recent wheezing. The adjusted OR
      and 95% confidence interval (CI) for any cough or phlegm symptoms was 1.19 (95%
      CI: 1.01-1.47) for one smoking household member, 1.38 (95% CI: 1.07-1.79) for two
      and 1.85 (95% CI: 1.19-2.85) for three (P for trend <0.001). Increased OR were
      found for father and mother smoking. CONCLUSIONS: This study provides strong
      evidence that both active and passive smoking can cause respiratory ill health in
      Chinese children in Hong Kong. Urgent measures are needed to protect children
      from the health hazards of active and passive smoking in Asia.

PMID- 9563693
TI  - Relationship between lung function and blood pressure in Chinese men and women of
      Beijing and Guangzhou. PRC-USA Cardiovascular and Cardiopulmonary Epidemiology
      Research Group.
AB  - BACKGROUND: Previous studies of western populations have shown an inverse
      association between lung function and blood pressure. METHODS: As part of a
      People's Republic of China-United States cardiopulmonary epidemiology study, we
      investigated the cross-sectional relationship between lung function and blood
      pressure in 6757 Chinese men and women, aged 35-54, from Beijing and Guangzhou,
      China. We also evaluated the longitudinal association between lung function and
      incident hypertension among 4818 initially normotensive subjects followed up
      between 2 and 4 years later. RESULTS: In our cross-sectional analyses of baseline
      data, lung function varied inversely with baseline systolic (SBP) and diastolic
      blood pressure (DBP) in all women and in Beijing men. This association held for
      absolute and height-standardized forced vital capacity (FVC) and one-second
      forced expiratory volume (FEV1) (correlations: 0.10, -0.18, P < 0.0001), but was
      weaker after adjustment for age (correlations: -0.02, -0.11). The longitudinal
      follow-up showed that lower initial lung function levels were associated with a
      higher incidence of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg or
      currently using antihypertensive medications), but only among women in Guangzhou.
      Relative risks for hypertension incidence for those in the two lowest quintiles
      for FEV1 and FVC, compared to those in the two highest quintiles, ranged from 1.9
      to 2.3 for Guangzhou women and from 0.9 to 1.4 for all other gender-city
      subgroups. Logistic regression analyses adjusting for age, baseline SBP, body
      mass index, smoking, education, and urban versus rural setting generally
      confirmed these patterns. CONCLUSIONS: These results suggest a statistically
      significant, though weak, inverse relationship between lung function and blood
      pressure in Chinese men and women. This association is largely attributable to
      age and is present prospectively only in women.

PMID- 9563694
TI  - The influence of socioeconomic status, ethnicity and lifestyle on body mass index
      in a longitudinal study.
AB  - BACKGROUND: Few studies have attempted to disentangle the complex relationship
      between socioeconomic status (SES) and ethnicity and its influence on body mass
      index (BMI) and on change in BMI over a decade. The present study highlights the
      influence of ethnicity (country of birth) and SES on BMI, adjusting for certain
      lifestyle factors. METHODS: The longitudinal self-reported data, based on a
      simple random sample, were obtained from 1972 women and 1871 men, aged 25-74,
      interviewed in 1980/81 and re-interviewed in 1988/89 using the same
      questionnaire. The influence of the independent variables on BMI was analysed by
      the Generalized Estimation Equation (GEE) method. The change in BMI for different
      states of the independent variables was analysed in a linear model with the
      difference in BMI between 1988/89 and 1980/81 as dependent variable, by sex.
      RESULTS: There was a graded relationship between male SES, defined as educational
      status, and BMI when adjusted for background variables, while for females, only a
      low educational level was associated with a higher BMI. Southern European men and
      Finnish women showed a higher increase in BMI than the reference group (Swedes
      and West Europeans) when adjusted for age, smoking, exercise, education, marital
      status, and health status. Not taking exercise was related to a higher BMI
      compared with those who were taking exercise. The BMI levels and smoking habits
      were little changed between 1980/81 and 1988/89, while exercise habits showed a
      more variable pattern. When the focus was on change in BMI, former smokers had a
      larger increase in BMI than never smokers. Further, men who ceased taking
      exercise had a larger increase in BMI than those who were taking regular exercise
      on both occasions. CONCLUSION: When adjusted for smoking and the other background
      variables, SES and ethnicity are two separate independent factors influencing BMI
      in men and women. When the focus was on change in BMI, former smokers had a
      larger increase in BMI than never smokers. Further, men who ceased taking
      exercise had a larger increase in BMI than those who took regular exercise on
      both occasions.

PMID- 9563695
TI  - Maternal exposure to prescription and non-prescription pharmaceuticals or drugs
      of abuse and risk of craniosynostosis.
AB  - BACKGROUND: The pre- and peri-natal drug exposures reported by women
      participating in a case-control study of children in Colorado were examined for
      association with infant craniosynostosis. METHODS: Mothers of case and control
      children underwent a standardized telephone interview and obstetric and newborn
      medical record review. The interview included questions on the use of
      prescription and non-prescription drugs, nutritional supplements, recreational
      and drugs of abuse. The mother's obstetric record was abstracted for information
      about pharmacologic agents taken before and during the antepartum period.
      RESULTS: There were no statistically significant risk ratios associating
      craniosynostosis with prenatal exposure to hydantoin, valproic acid, or cocaine.
      Mothers of four case children and one control child reported specific exposure to
      retinoic acid. There were no statistically significant increases in the odds
      ratio (OR) for any suture type among children exposed to hypoxigenic agents,
      sympathomimetic or parasympatholytic agents, or metal-containing agents. The OR
      was 1.87 (lower bound of the two-sided 95% test-based confidence interval (CI):
      1.08) among children with sagittal/lambdoid suture synostosis who were exposed to
      nitrosatable drugs chlorpheniramine, chlordiazepoxide, and nitrofurantoin
      compared to controls. CONCLUSIONS: Certain nitrosatable drugs may be associated
      with increased risk of infant sagittal/lambdoid craniosynostosis. A possible
      mechanism related to ischaemia/reperfusion injury is suggested.

PMID- 9563696
TI  - The relationship of interpregnancy interval to the risk of preterm births to
      black and white women.
AB  - BACKGROUND: Premature births are of major public health concern. Short
      interpregnancy intervals may influence the incidence of premature births among
      black and white women, with blacks conceiving at shorter intervals than whites.
      DESIGN: Women (293 blacks and 468 whites) with complete obstetric records
      delivering singleton infants between January 1988 and December 1993 were
      included. We related the outcome of the second of any pair of consecutive
      pregnancies to the interval between the pair. RESULTS: Both black and white women
      conceiving within 3 months or less of their preceding pregnancy had a high risk
      of premature birth (37.5%). At all other intervals, the risk among blacks was
      consistently over twice that for whites. Conception within an interval of 6
      months or less was significantly associated with increased risk of premature
      birth for blacks (35.8% versus 25.8% for longer intervals; P = 0.03), but this
      difference was not significant after controlling for other confounding variables
      (odds ratio = 1.52, 95% confidence interval [CI]: 0.91-2.55). Whites conceiving
      within 6 months compared to those conceiving after more than 6 months had no
      significant increased risk (18.4% versus 9.7%). The risk of preterm birth was
      1.67 (CI: 0.42-2.91) for women conceiving at < or =6 months, compared to those
      who conceived after 6 months, after controlling for confounding variables.
      CONCLUSIONS: Preterm birth was not significantly associated with short intervals
      of 6 months or less for both black and white women. A subset of multiparous black
      women with short interpregnancy intervals, however, may have an increased risk of
      premature birth.

PMID- 9563697
TI  - Stillbirth rates around the nuclear installation at Sellafield, North West
      England: 1950-1989.
AB  - BACKGROUND: The aim of the study was to investigate whether proximity to the
      nuclear installation at Sellafield, in Cumbria, North West of England, increases
      the risk of stillbirth in the resident population. The cohort consisted of all
      256066 live and 4034 stillbirths to mothers usually domiciled in Cumbria, 1950
      1989. METHODS: The study was a retrospective cohort analysis allowing for year of
      birth, social class and birth order using: (i) Poisson probability mapping, (ii)
      comparison of cumulative observed and expected numbers of stillbirths by distance
      from Sellafield, (iii) logistic regression of stillbirth risk in relation to
      distance and direction from Sellafield. RESULTS: Poisson probability mapping of
      stillbirths within 25 km of Sellafield provided no evidence to suggest that
      proximity to Sellafield increased the risk of stillbirth, either overall or in
      any specific direction. Comparison of the cumulative observed and expected
      numbers of stillbirths also showed no increased risk with proximity to
      Sellafield. Logistic regression analysis of all Cumbrian births supported these
      results, showing, in particular, that distance from Sellafield did not
      significantly influence stillbirth risk (P = 0.30). Although there was
      significant variation in stillbirth risk with direction (P = 0.0004), this was
      due to stillbirths in areas much further than 25 km from Sellafield. There was no
      significant effect with distance from Sellafield within any of six directional
      sectors (P > 0.05). CONCLUSIONS: There was no evidence to suggest that proximity
      to Sellafield increases the risk of stillbirth in the resident population.

PMID- 9563698
TI  - Gestational-age-specific stillbirth risk among Australian Aborigines.
AB  - BACKGROUND: Previous studies have found that, for preterm babies, the risk of
      stillbirth among Australian Aborigines is similar to the risk for whites. In
      contrast, at full term, the risk for Aborigines is more than twice the risk for
      whites. However, these studies (like most other analyses of stillbirths) used the
      number of births at each gestational age to calculate the risk. For stillbirths,
      the risk is more appropriately estimated using the number of babies in utero.
      This paper presents the first comparison of stillbirth risk for Australian
      Aborigines and whites using the more appropriate denominator. METHODS: I used 6
      years of data (1987-1992) from the routinely-maintained Queensland Perinatal Data
      Collection. Contingency-table analyses were used to compare the gestational-age
      specific risk of stillbirth in Aborigines and whites. Multiple births were
      excluded; male and female babies were analysed separately. RESULTS: When the
      number of babies in utero was used as the denominator, preterm Aborigines had a
      statistically significant three- to fourfold increase in the risk of stillbirth
      compared with whites. At full term, the risks for Aborigines and whites were not
      statistically significantly different. CONCLUSIONS: A different pattern of
      gestational-age-specific stillbirth risk was obtained when the appropriate
      denominator was used. Specifically, the high risk of stillbirth for preterm
      Aborigines was revealed. Research is needed to identify the causes of the
      Aboriginal-white difference in stillbirth risk for preterm babies.

PMID- 9563699
TI  - The impact on prevalence of dementia in the oldest age groups of differential
      mortality patterns: a deterministic approach.
AB  - BACKGROUND: Until recently relatively little data have been available on the
      prevalence of dementia in the oldest age groups, and yet it is these age groups
      which are expanding fastest. It is therefore important to understand whether the
      prevalence of dementia rises inexorably with age ('age-dependent'), or, as some
      suggest, levels off or even declines in the very oldest age groups ('age
      related'). Combined analysis of the many prevalence studies now available has led
      to modelled curves which do suggest a slowing of rise in prevalence at these
      great ages, and has been interpreted as meaning that dementia is age-related.
      This interpretation does not take into account the differential survival of
      individuals with cognitive impairment compared with normals of the same age.
      METHOD: Flexible prevalence-incidence-duration models were generated using a
      deterministic approach applied to published combined analyses of prevalence
      rates, population death rates and mortality odds ratios. RESULTS: The variation
      in observed prevalence patterns with age is explained to a great extent by the
      mortality observed in the cognitively impaired. Simple examination of age
      patterns in prevalence does not answer the fundamental question surrounding the
      age-dependence of cognitive impairment. CONCLUSION: Inferring biological meaning
      from these observed curves is not valid without examining the mathematical
      phenomena of the relationship of incidence, mortality and prevalence. This
      approach allows an examination of the impact of varying mortality and incidence
      on the prevalence of dementia and cognitive impairment and will be useful in
      determining the potential impact of preventive strategies on the population.

PMID- 9563700
TI  - Prevalence proportion ratios: estimation and hypothesis testing.
AB  - BACKGROUND: Recent communications have argued that often it may not be
      appropriate to analyse cross-sectional studies of prevalent outcomes with
      logistic regression models. The purpose of this communication is to compare three
      methods that have been proposed for application to cross sectional studies: (1) a
      multiplicative generalized linear model, which we will call the log-binomial
      model, (2) a method based on logistic regression and robust estimation of
      standard errors, which we will call the GEE-logistic model, and (3) a Cox
      regression model. METHODS: Five sets of simulations representing fourteen
      separate simulation conditions were used to test the performance of the methods.
      RESULTS: All three models produced point estimates close to the true parameter,
      i.e. the estimators of the parameter associated with exposure had negligible
      bias. The Cox regression produced standard errors that were too large, especially
      when the prevalence of the disease was high, whereas the log-binomial model and
      the GEE-logistic model had the correct type I error probabilities. It was shown
      by example that the GEE-logistic model could produce prevalences greater than
      one, whereas it was proven that this could not happen with the log-binomial
      model. The log-binomial model should be preferred.

PMID- 9563701
TI  - Measuring morbidity of children in the community: a comparison of interview and
      diary data.
AB  - BACKGROUND: Little is known about the validity of estimates of morbidity
      experienced at home. METHODS: In the Dutch National Survey of Morbidity and
      Interventions in General Practice mothers of 1630 children answered a health
      interview and kept a health diary for 3 weeks (only the first 2 weeks were used).
      Children's symptoms were recorded during the interview using a check list and
      monitored in the health diary through open-ended questions. RESULTS: In the
      interview parents reported symptoms for 65% of their children and in the diary
      for 54% of children. Ear problems, colds, fever and weakness and anxiety were
      reported more often in the interview. Mother's mental health was assessed by the
      General Health Questionnaire; those scoring >4 were assessed as having impaired
      mental health and these parents reported symptoms for more children in the
      interview (81%) than in the diary (65%). For similar reference periods, the least
      educated mothers reported fewer children with symptoms in the diary (45%) than in
      the interview (66%). More highly educated mothers reported similarly in the diary
      (67%) and the interview (70%). CONCLUSION: Both data collection methods yield
      different estimates of community morbidity. Explanations such as telescoping, the
      seriousness of the symptoms, the amount of psychological distress of the
      respondent, forgetfulness and literacy limitations are discussed. We recommend
      that diaries should not be used in less educated populations.

PMID- 9563702
TI  - Provisional country estimates of prevalent adult human immunodeficiency virus
      infections as of end 1994: a description of the methods.
AB  - BACKGROUND: A country-by-country review of human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome (AIDS) data was undertaken by the World
      Health Organization. This paper describes the methods used to make estimates of
      HIV prevalence. RESULTS: It is estimated that, globally, approximately 16.9
      million adults were living with HIV infections at the end of 1994. The majority
      (66%) of the infections were in sub-Saharan Africa (over 11000000), followed by
      South and South East Asia (over 3000000). Estimated prevalence rates for HIV
      infection ranged from less than 1 per 100000 sexually active adult population to
      18 per 100 (18%), with a median prevalence of 14 per 10000. In 50 countries the
      estimated HIV prevalence rate was less than 5 per 10000 sexually active adults.
      In 15 countries (all in sub-Saharan Africa) the prevalence rate was above 5%. The
      lowest estimated prevalence rates were seen in Central and East Asia and the
      highest in Central and Southern Africa. CONCLUSIONS: Estimates of prevalent HIV
      infections are intended to give an indication of the magnitude of the HIV
      pandemic but, due to the difficulties in accurately assessing the levels of HIV
      infections in national populations, should be considered provisional.

PMID- 9563703
TI  - A review of hepatitis C virus (HCV) vertical transmission: risks of transmission
      to infants born to mothers with and without HCV viraemia or human
      immunodeficiency virus infection.
AB  - BACKGROUND: Hepatitis C virus (HCV) vertical transmission studies have reported
      conflicting findings, possibly due to differences in HCV transmission risk
      factors among maternal populations, or to methodological differences. METHODS:
      Systematic review of worldwide published and unpublished HCV vertical
      transmission studies. Standardized diagnostic criteria were applied to minimize
      methodological differences, and transmission rates recalculated according to
      maternal HCV viraemic and human immunodeficiency virus (HIV) infection status.
      RESULTS: In all, 976 eligible infants from 28 studies were followed up
      sufficiently for recalculation of transmission rates. Overall transmission rates
      were less than 10% in 8/12 studies of HIV negative mothers, compared with 2/7
      studies comprising at least 50% HIV-coinfected mothers. Rates from 409 viraemic
      mothers in 15 studies ranged from 0% to 41%, being less than 10% from HIV
      negative mothers in 6/13 studies and from HIV positive mothers in 1/6 studies.
      Nine studies measured maternal viraemia levels, with only 2/30 transmitting
      mothers having < 10(6) copies/ml of HCV RNA. Eight transmissions were identified
      overall from non-viraemic mothers. Significant transmission rate variation
      remained after accounting for maternal viraemia and HIV coinfection, possibly due
      to differences in other vertical transmission risk factors, in frequencies of
      postnatal transmission, or residual differences in study methodologies.
      CONCLUSIONS: Overall, HCV transmission is largely restricted to infants born to
      HCV viraemic mothers, and low risks among most HIV negative mothers may be due to
      lower HCV viraemia levels. International agreement on standardized diagnostic
      criteria for HCV vertical transmission would facilitate pooling of individual
      findings, to allow more precise transmission estimates and further investigation
      of risk factors.

PMID- 9563704
TI  - The prevalence of hepatitis A antibodies among Israeli travellers and the
      economic feasibility of screening before vaccination.
AB  - BACKGROUND: Hepatitis A (HA) is the most common vaccine-preventable disease among
      travellers. The probability of contracting the disease depends on the endemicity
      in both the destination and country of origin of the traveller. The introduction
      of the new highly effective but expensive inactivated HA vaccine necessitates a
      re-evaluation of HA prevention policy. In highly developed countries all
      travellers require vaccination. In highly endemic areas the entire population is
      immune. In Israel, HA seroprevalence declined from 94% in the early 1970s to <
      60% in the mid 1980s. Living in a country in which the HA endemicity is changing,
      we studied the current situation of HA seroprevalence among travellers and the
      cost-benefit of screening for HA IgG before vaccination. METHODS: Israeli
      travellers of all ages, (range 22-74 years) expecting to spend a considerable
      time abroad presented to the travel clinic for pre travel advice and vaccination.
      A brief medical history was taken, including history of jaundice. Blood for HA
      IgG testing was drawn. RESULTS: In the present study, 389 Israeli travellers were
      screened for HA IgG. Overall, 46% were seropositive: 26% in the 21-30 group (n =
      102); 37% in the 31-40 group (n = 145); 62% in the 41-50 group (n = 62); and 79%
      in the > 50 group (n = 80). CONCLUSIONS: In countries where hepatitis A
      endemicity is changing, an evaluation of seroprevalence and then a cost benefit
      calculation should be made. In Israel, assuming a current cost of $130 for
      vaccination and $30 for the IgG test, it is economically valid to screen Israeli
      travellers > 30 years old for HAV IgG before vaccination. A formula is presented
      for calculating the cost benefit ratio in any country, based on local endemicity
      according to age group.

PMID- 9563705
TI  - Epidemiology of drug-resistant tuberculosis in New Jersey from 1991 to 1995.
AB  - BACKGROUND: In a nationwide survey in 1991, the proportion of Mycobacterium
      tuberculosis isolates resistant to both isoniazid and rifampin (MDR-TB) in New
      Jersey (6.6%) was ranked second highest in the United States. The objectives of
      this study were to describe drug-resistant TB trend and to investigate risk
      factors for TB patients with isolates resistant to isoniazid or rifampin or both.
      METHODS: TB surveillance data in New Jersey from 1991-1995 were analysed. Data on
      Mycobacterium tuberculosis culture and drug susceptibility testing of all TB
      isolates were obtained from public health and clinical laboratories. Logistic
      regression was performed to calculate odds ratios (OR) and 95% confidence
      intervals (CI) and to adjust for potential confounders. RESULTS: From 1991 to
      1995, the proportion of MDR-TB was 5.7%, 4.1%, 2.7%, 3.3% and 2.6%, respectively.
      There was 10.6% isoniazid resistance and 4.3% rifampin resistance among TB
      patients in 1993-1995. As expected, recurrent TB was the most important risk
      factor for resistance to isoniazid (OR = 4.5, 95% CI: 2.6-7.6), rifampin (OR =
      5.5, 95% CI: 2.8-11) or both (OR = 6.1, 95% CI: 2.9-13). HIV infection was
      significantly associated with MDR-TB (OR = 3.6, 95% CI: 1.5-8.8). Drug resistance
      was not found to be significantly associated with homelessness, injecting drug
      use and excess alcohol use. CONCLUSIONS: The proportion of MDR-TB in New Jersey
      declined significantly from 1991 to 1993, but remained at a plateau from 1993
      1995. The results suggest that continuous efforts should be directed at the
      prevention of MDR-TB among people infected with HIV and at improving the
      proportion who complete chemotherapy among those with TB.

PMID- 9563707
TI  - Prevalence and determinants of Helicobacter pylori infection in preschool
      children: a population-based study from Germany.
AB  - BACKGROUND: Helicobacter pylori is among the most common infections in humans and
      has been recognized as major cause of various gastroduodenal diseases. There is
      limited knowledge, however, on the prevalence and determinants of this infection
      in children. We addressed these issues in a population-based cross-sectional
      study in Southern Germany. METHODS: Study subjects were all preschool children in
      Ulm, a city in the South of Germany, who were screened for school fitness by
      physicians of the public health service in 1996. Infection status was determined
      by 13C-urea breath test. In addition, the parents of the children were asked to
      fill out a standardized questionnaire. RESULTS: In total, 945 out of the 1201
      eligible preschool children participated in the study (response rate = 79%). The
      children were aged 5-8 years. The majority were of German nationality (72.6%).
      Overall, 127 children (13.4%) were infected with H. pylori. Nationality, place of
      residence in the first year of life and duration of living in Germany were
      strongly associated with H. pylori infection status. The prevalence varied from
      4.8% (95% confidence interval [CI]: 3.3-6.8%) in children with German nationality
      who were born in Germany or had lived in Germany since their first year of life
      to 66.7% (95% CI: 29.9-92.5%) in the children with Turkish nationality who came
      to Germany after the first year of life. CONCLUSION: Our results showed a large
      variation in prevalence of H. pylori infection in children living in the same
      geographical area according to nationality. They indicate an association between
      living conditions in early childhood and H. pylori infection and indicate that H.
      pylori associated morbidity may evolve very differently in population subgroups
      living in the same area.

PMID- 9563706
TI  - Prevalence and correlates of herpes simplex virus type 2 infection: evaluation of
      behavioural risk factors.
AB  - OBJECTIVE: To examine the prevalence and correlates of infection with herpes
      simplex virus type 2 (HSV-2) among sexually transmitted disease (STD) clinic
      attenders, we studied the prevalence of antibodies to HSV-2 and their association
      with risk behaviour. METHODS: Data were collected in a cross-sectional study
      among STD clinic attenders in Amsterdam. Seropositivity for HSV-2 was determined
      in 1798 serum samples by means of a monoclonal antibody-blocking enzyme-linked
      immunoassay. RESULTS: The prevalence of HSV-2 antibodies was higher than
      expected: 32.3% in a population in which 3% had current genital herpes and 8%
      gave a history of genital herpes. Of those with HSV-2 antibodies, only 18% had a
      history of genital herpes. A strong independent association with the presence of
      HSV-2 antibodies was found for sexual behaviour, more specifically: homosexual
      orientation, increasing number of years of sexual activity, increasing number of
      lifetime partners, number of past gonococcal infections, having receptive anal
      and (or) vaginal contact. CONCLUSION: The presence of HSV-2 antibodies had a
      strong association with past sexual behaviour and, for both sexes, with receptive
      anal intercourse. HSV-2 antibodies may be used as a surrogate marker of sexual
      risk behaviour in comparing different populations over time.

PMID- 9563708
TI  - High seroprevalence of Coxiella burnetii infection in Eastern Cantabria (Spain).
AB  - BACKGROUND: Coxiella burnetii is the causative agent of Q fever, a worldwide
      zoonosis which shows a wide diversity of clinical manifestations. The objective
      of this seroepidemiological study was to estimate the prevalence of antibodies to
      C. burnetii in a representative population of the Eastern area of the Cantabrian
      Community (Northern Spain). METHODS: A cross-sectional study was conducted in 595
      subjects from Eastern Cantabria. Four different zones (one urban and three rural
      zones) were defined according to the geographical characteristics of the area and
      the economic activities of the population. The population sample for this study
      was collected between December 1994 and March 1995, and was stratified by age,
      sex and municipality of residence. IgG and IgM antibodies against C. burnetii
      were assayed by an indirect immunofluorescence technique. RESULTS: The prevalence
      of anti-phase II Coxiella IgG (titre > or = 1:16) was 48.6% (95% confidence
      interval: 44.6-52.6%), with 81.3% havinga titre of > or = 1:64. The prevalence of
      IgG increased with age, ranging from 12.0% in people < 15 years to 70.3% in those
      > 65 years (P < 0.001). The antibody detection rate was higher in males (53.6%)
      than in females (43.3%) (P < 0.01). The prevalence of anti-phase II Coxiella IgG
      was less among subjects living in the urban zone (32.8%) than in those living in
      the other three rural zones: the two situated on the coast (54.0% and 54.9%
      respectively) and the inner mountainous zone (82.3%) (P < 0.001). CONCLUSIONS:
      The prevalence of C. burnetii infection observed in this study is one of the
      highest reported in Europe. The eastern area of Cantabria is a hyperendemic area
      for Q fever.

PMID- 9563709
TI  - Intrafamilial clustering and 4-year follow-up of asymptomatic human T-cell
      leukaemia virus type I (HTLV-I) infection in Benin (West Africa).
AB  - BACKGROUND: Few data exist concerning familial human T-cell leukaemia virus type
      I (HTLV-I) carrier states and transmission in African countries. Two previous
      surveys performed in Benin in 1989 and 1990 using a three-level cluster sampling
      method allowed us to identify HTLV-I positive subjects. The evolution of HTLV-I
      within the families of these subjects is described over a 4-year period, 1991
      1995. METHODS: Since 1991, 37 HTLV-I seropositive subjects, six subjects with
      indeterminate Western-Blot pattern, and their relatives have been followed up
      once a year clinically and biologically. RESULTS: Twenty-three mothers in the
      study group gave birth to 27 children between 1991 and 1995. Among the 13 infants
      born to the 12 seropositive mothers, two seroconverted before their second
      birthday. One adult woman whose husband was seropositive developed seropositivity
      4 years after marriage. In March 1992, a family case-control study (proband
      study) was conducted. A seroprevalence of 27.5% was found among 138 relatives of
      32 infected subjects and 1.4% among 142 relatives of 32 control subjects.
      CONCLUSIONS: There is clearly an intrafamilial clustering of HTLV-I in Benin. The
      annual incidence density of HTLV-I in this cohort is estimated at 6 per thousand.

PMID- 9563710
TI  - Lifestyle factors and stomach cancer.

PMID- 9563711
TI  - Tuberculosis: poverty's penalty.

PMID- 9563712
TI  - Training pulmonary and critical care physicians in outcomes research: should we
      take the challenge?

PMID- 9563713
TI  - Tuberculosis and race/ethnicity in the United States: impact of socioeconomic
      status.
AB  - Despite the long-standing observation that tuberculosis (TB) case rates are
      higher among racial and ethnic minorities than whites in the United States
      (U.S.), the proportion of this increased risk attributable to socioeconomic
      status (SES) has not been determined. Values for six SES indicators (crowding,
      income, poverty, public assistance, unemployment, and education) were assigned to
      U.S. TB cases reported from 1987-1993 by ZIP code- and demographic-specific
      matching to 1990 U.S. Census data. TB risk between racial/ethnic groups was then
      evaluated by quartile for each SES indicator utilizing univariate and Poisson
      multivariate analyses. Relative risk (RR) of TB increased with lower SES quartile
      for all six SES indicators on univariate analysis (RRs 2.6-5.6 in the lowest
      versus highest quartiles). The same trend was observed in multivariate models
      containing individual SES indicators (RRs 1.8-2.5) and for three SES indicators
      (crowding, poverty, and education) in the model containing all six indicators.
      Tuberculosis risk increased uniformly between SES quartile for each indicator
      except crowding, where risk was concentrated in the lowest quartile. Adjusting
      for SES accounted for approximately half of the increased risk of TB associated
      with race/ethnicity among U.S.-born blacks, Hispanics, and Native Americans. Even
      more of this increased risk was accounted for in the final model, which also
      adjusted for interaction between crowding and race/ethnicity. SES impacts TB
      incidence via both a strong direct effect of crowding, manifested predominantly
      in overcrowded settings, and a TB-SES health gradient, manifested at all SES
      levels. SES accounts for much of the increased risk of TB previously associated
      with race/ethnicity.

PMID- 9563714
TI  - Mild hyperlactatemia in stable septic patients is due to impaired lactate
      clearance rather than overproduction.
AB  - A prospective study was conducted on 34 stable septic patients to determine
      whether mild hyperlactatemia is a marker of lactate overproduction or an
      indicator of lactate underutilization during sepsis. Plasma lactate clearance and
      lactate production were evaluated by modeling the lactate kinetic induced by an
      infusion of 1 mmol/kg L-lactate over 15 min. The patients were divided in two
      groups depending on their blood lactate: < or = 1.5 mmol/L (n = 20, lactate =
      1.2+/-0.2 mmol/L) or > or = 2 mmol/L (n = 10, lactate = 2.6+/-0.6 mmol/L). The
      hyperlactatemic patients had a lower lactate clearance (473+/-102 ml/kg/h) than
      those with normal blood lactate (1,002+/-284 ml/kg/h, p < 0.001), whereas lactate
      production in the two groups was similar (1,194+/-230 and 1,181+/-325
      micromol/kg/h, p = 0.90). A second analysis including all the patients confirmed
      that the blood lactate concentration was closely linked to the reciprocal of
      lactate clearance (r2 = 0.73, p < 0.001) but not to lactate production (r2 =
      0.03, p = 0.29). We conclude that a mild hyperlactatemia occurring in a stable
      septic patient is mainly due to a defect in lactate utilization.

PMID- 9563715
TI  - Lipopolysaccharide-induced alveolar epithelial permeability: the role of nitric
      oxide.
AB  - Intratracheal instillation of lipopolysaccharide (LPS) in the rat has been used
      as a model of acute lung inflammation. Among the early events in this process is
      a transient increase in airspace epithelial permeability which peaks 4 h after
      intratracheal instillation of LPS. The increased epithelial permeability is
      concomitant with the influx of neutrophils into the airspaces, peaking 8 h
      postinstillation. We have investigated the mechanism of this LPS-induced increase
      in epithelial permeability. The role of the neutrophil in LPS-induced epithelial
      permeability was assessed by pretreatment with neutrophil antibody to abolish
      neutrophil influx, which did not affect the increase in epithelial permeability.
      Because LPS instillation also induced increased tumor necrosis factor alpha (TNF
      alpha) activity in bronchoalveolar lavage (BAL) fluid, and its release by
      cultured BAL leukocytes from treated animals, TNF-alpha antibody was coinstilled
      intratracheally with LPS in rats. TNF-alpha antibody eliminated TNF-alpha
      activity in BAL fluid, but had no effect on LPS-induced increased epithelial
      permeability. Increased levels of nitric oxide (NO), measured as nitrite, were
      also present in BAL fluid from LPS-treated rat lungs and LPS-elicited BAL
      leukocytes produced increased NO in culture. Treatment of rats with the specific
      NO synthase inhibitor L-NMMA significantly diminished the LPS-induced increased
      epithelial permeability. These data suggest that NO is involved in LPS-induced
      changes in epithelial integrity. However, other mechanisms should be evoked in
      addition to NO to explain completely the increased epithelial permeability
      produced by LPS.

PMID- 9563716
TI  - Acute effects of ambient inhalable particles in asthmatic and nonasthmatic
      children.
AB  - Although increases in inhalable particle (PM10) concentrations have been
      associated with acute reductions in the level of lung function and increased
      symptom reporting in children, including children with asthma, it is not clear
      whether these effects occur largely in asthmatic children, or even whether
      asthmatic children are more likely to experience these effects than children
      without asthma. To address these points, the following subgroups of children were
      selected from a survey population of all 2,200 elementary school children (6 to
      13 yr of age) in a pulp mill community on the west coast of Vancouver Island: (1)
      all children with physician-diagnosed asthma (n = 75 participated), (2) all
      children with an exercise-induced fall in FEV1 without diagnosed asthma (n = 57),
      (3) all children with airway obstruction (FEV1/FVC < 0.76) without either of the
      above (n = 18), and (4) control children without any of the above (n = 56). The
      children were followed for as long as 18 mo with twice daily measurements of peak
      expiratory flow (PEF) and daily symptom diary recording. Maximum daily PM10
      concentration was 159 microm/m3 (median, 22.1), but only 8 d (1.2%) had
      concentrations above 100 microg/m3. In an analysis that accounted for time
      varying covariates, and serially correlated and missing data, for the entire
      sample of children, increases in PM10 were associated with reductions in PEF and
      increased reporting of cough, phlegm production, and sore throat. For the
      subgroup of children with diagnosed asthma, PEF in the time period with the
      highest PM10 concentrations fell by an estimated 0.55 L/min (95% CI, 0.06 to
      1.05) for a 10 microg/m3 PM10 increase above the mean daily PM10 concentration of
      27.3 microg/m3 and the odds of reported cough increased by 8% (95% CI, 0 to 16%);
      no consistent effects were observed in the other groups of children. It is
      concluded that children experience reductions in PEF and increased symptoms after
      increases in relatively low ambient PM10 concentrations, and that children with
      diagnosed asthma are more susceptible to these effects than are other children.

PMID- 9563717
TI  - Static intrinsic PEEP in COPD patients during spontaneous breathing.
AB  - Intrinsic positive end-expiratory pressure (PEEPi) is routinely determined under
      static conditions by occluding the airway at end-expiration (PEEPi,st). This
      procedure may be difficult in patients with chronic obstructive pulmonary disease
      (COPD) during spontaneous breathing, as both expiratory muscle activity and
      increased respiratory frequency often occur. To overcome these problems, we
      tested the hypothesis that the difference between maximum airway opening (MIP)
      and maximum esophageal (Ppl max) pressures, obtained with a Mueller maneuver from
      the end-expiratory lung volume (EELV), can accurately measure PEEPi,st. Using
      this method, we found that, in eight ventilator-dependent tracheostomized COPD
      patients (age 71+/-7 yr), PEEPi,st averaged 13.0+/-2.9 cm H2O. That measurement
      was validated by comparison with a reference static PEEPi (PEEPi,st-Ref) taken at
      the same EELV adopted by patients during spontaneous breathing, and measured on
      the passive quasi-static pressure-volume (P/V) curve of the respiratory system,
      obtained during mechanical ventilation. PEEPi,st-Ref averaged 13.1+/-3.0 cm H2O,
      i.e., a value essentially equal to PEEPi,st measured by means of our technique.
      We conclude that PEEPi,st can be accurately assessed in spontaneous breathing
      COPD patients by the difference between MIP and Ppl max during the Mueller
      maneuver.

PMID- 9563718
TI  - The hypotonic upper airway in obstructive sleep apnea: role of structures and
      neuromuscular activity.
AB  - The structural properties of the upper airway determine its collapsibility during
      periods of muscle hypotonia. Both rapid-eye-movement (REM) sleep and increases in
      nasal pressure (PN) produce hypotonia, which persists even after nasal pressure
      is abruptly reduced. To determine the factors that influence the collapsibility
      of the hypotonic airway, the critical pressure (Pcrit) and nasal resistance
      upstream to the site of pharyngeal collapse (RN) were measured in the first three
      breaths after abrupt reductions in PN during non-REM and REM sleep. PN was
      reduced abruptly from 15.2+/-3.2 cm H2O (mean +/- SD) for three breaths in 19
      apneic patients. Upper-airway pressure-flow relationships were analyzed to
      determine Pcrit for each breath in non-REM and REM sleep. We found that Pcrit
      rose (collapsibility increased, p < 0.001) and RN fell (p = 0.02) between the
      first and third breath after the decrease in PN, whereas no difference in Pcrit
      was detected between sleep stages. In six patients, genioglossus-muscle
      electromyograms (EMGs) were recorded. Peak phasic activity rose between the first
      and third breath (p = 0.03), but tonic and peak phasic EMG activity fell in REM
      as compared with non-REM sleep (p < 0.001). We conclude that the hypotonic upper
      airway becomes most collapsible by the third breath after an abrupt decrease in
      PN, regardless of sleep stage and despite an increase in genioglossus-muscle
      activity. Our findings suggest that predominantly mechanical rather than
      neuromuscular factors modulate the properties of the pharynx after abrupt
      reductions in nasal pressure.

PMID- 9563719
TI  - The effects of acid perfusion of the esophagus on ventilation and respiratory
      sensation.
AB  - The relationship between gastroesophageal reflux (GER) and asthma remains
      controversial. Asthma symptoms worsen with GER, but are not consistently related
      to changes in lung function. The purpose of this study was to determine whether
      acid perfusion (AP) of the esophagus alters ventilation and causes respiratory
      symptoms. Nonasthmatic patients with normal lung function and esophageal disease
      (16 females and nine males, FEV1 %predicted = 99+/-9.6), underwent a Bernstein
      test after motility testing. Airflow, rib cage (Vrc), and abdominal (Vab) tidal
      volumes, esophageal (Pes) and gastric (Pga) pressure, and surface (Es) and
      esophageal (Edi) diaphragm electromyographic (EMG) signals were measured. Throat,
      swallowing, chest, and stomach discomfort and respiratory sensation were
      estimated with the Borg scale. Minute ventilation (VE) increased during AP and
      declined during recovery with saline perfusion of the esophagus (7.1+/-1.5 to
      8.5+/-2.4 to 7.3+/-2.1 L/min; n = 25; p = 0.0002). Respiratory rate (RR) went
      from 13.6+/-2.6 to 15.8+/-3.4 to 15.3+/-3.1 breaths/min (n = 25; p = 0.0002)
      during AP. VE was greater in the Bernstein-positive patients during AP. Tidal
      volume (VT), Vrc, Vab, Pes, Pga, Es, and Edi did not change during AP. Chest
      discomfort (D) correlated with ventilation (VE = 0.7 + 0.8 D; r = 0.67; p <
      0.001) and respiratory effort sensation (B) (B = 0.2 + 0.4 VE; r = 0.70; p <
      0.001) during AP. AP did not inhibit diaphragm activity. Increased VE may explain
      the paradox of GER worsening respiratory symptoms without changing lung function.

PMID- 9563720
TI  - Idiopathic pulmonary fibrosis: predicting response to therapy and survival.
AB  - Idiopathic pulmonary fibrosis (IPF) is associated with significant morbidity and
      mortality despite aggressive therapy. Thirty-eight patients with biopsy-proven
      IPF were studied to identify pretreatment features that could be used to predict
      short-term improvement in pulmonary function and improved longer term survival.
      In all patients, a pretreatment clinical (dyspnea), radiographic (chest
      radiograph), and physiologic (pulmonary function including exercise saturation)
      score was generated (CRP). A high-resolution CT scan (HRCT) was independently
      scored by four radiologists for ground glass (CT-alv) and linear opacity (CT-fib)
      on a scale of 0-4. Open lung biopsy samples were scored for cellular
      infiltration, interstitial fibrosis, desquamation, and granulation by an
      experienced pulmonary pathologist. All patients were treated with 3 mo of high
      dose steroids and the CRP scoring repeated. Patients were divided into three
      groups: responders with a greater than 10-point drop in CRP (n = 10); stable with
      +/- 10 point change in CRP (n = 14); and nonresponders with > 10 point rise in
      CRP or death (n = 14). Those responding to steroids were treated for 18 mo in a
      tapering fashion. In all others, steroids were tapered quickly and oral
      cyclophosphamide prescribed. Responders (10 of 38) had a lower age (45.1+/-4.3
      yr) than nonresponders (61.4+/-3.5 yr) or those remaining stable (53.1+/-3.3 yr)
      (p = 0.01). Pretreatment CRP was higher in responders (58.8+/-5.6) than
      nonresponders (40.5+/-4.7) or stable individuals (37.6+/-4.7) (p = 0.01).
      Cellular infiltration score of the open lung biopsies was higher in responders
      (7.6+/-0.6) than stable individuals (5.7+/-0.5) (p = 0.04). The CT-alv scores
      were higher and CT-fib scores were lower in responders than nonresponders.
      Receiver operating curve (ROC) analysis was employed to identify pretreatment
      features of longer term survival (follow-up of 29.1+/-2.3 mo). Only CT-fib (p =
      0.009) and pathology fibrosis score (p = 0.03) were able to predict mortality. A
      pretreatment CT-fib score > or = 2.0 demonstrated 80% sensitivity and 85%
      specificity in predicting survival. Those patients who did not respond to initial
      steroid therapy demonstrated a worse long-term survival and greater likelihood of
      decreased pulmonary function. We demonstrate that pretherapy pulmonary function,
      pathologic and radiographic parameters are different in individuals who respond
      to initial prednisone therapy. Only HRCT imaging and pathologic fibrosis were
      able to reliably predict long-term survival in patients with biopsy-proven IPF.

PMID- 9563721
TI  - Importance of genetic factors in adolescent asthma: a population-based twin
      family study.
AB  - Gene-environment interactions and inheritance of asthma were studied in 16-yr-old
      twins and their parents who participated in the nationwide Finnish Twin Cohort
      Study. Between 1991 and 1994, questionnaires, including a question on physician
      diagnosed asthma, were mailed to the members of 2,483 twin families. The
      individual response rate ranged from 82 to 93%. Information on parental asthma
      status allowed the genetic modeling of asthma data in two different groups of
      twins. In families where one of the parents was asthmatic, as much as 87% of the
      variation in susceptibility to asthma in twins was explained by genetic factors.
      On the other hand, for twins whose parents were unaffected, a model including
      environmental effect alone was sufficient to explain the development of asthma.
      Genetic influences could not be totally excluded, but their role was
      significantly smaller. These results indicate that the presence of asthma in
      successive generations is more likely caused by shared genes than shared
      environmental risk factors; however, substantial heterogeneity among families may
      exist. Genetic analysis, especially among the families with an obvious familial
      component in development of asthma, may enhance the chances of revealing the
      pathogenetic mechanisms

PMID- 9563722
TI  - 20-year trends in the prevalence of asthma and chronic airflow obstruction in an
      HMO.
AB  - Although asthma is on the rise in the United States and elsewhere, data on age
      sex-specific patterns of change in various types of health care utilization are
      scarce. We report on 20-yr trends in the treated prevalence of asthma among
      members of a large health maintenance organization. Data are presented separately
      for each of six age-sex categories, and include both the treated prevalence of
      asthma as well as the treated prevalence of the broader category of chronic
      airflow obstruction (CAO), defined as asthma, chronic bronchitis, or emphysema.
      During the period 1967-1987 the treated prevalence of asthma and CAO increased
      significantly in all age-sex categories except males aged 65 and older. These
      patterns are in contrast to previous studies of this population that showed that
      increases in asthma hospitalizations and hospital-based episodes of care were
      limited primarily to young boys. Not only do these findings support other
      evidence of a real increase in asthma prevalence, but they also highlight the
      risks associated with drawing inferences about changing disease epidemiology
      based on a single type of health care utilization.

PMID- 9563723
TI  - Diaphragm function during sighs in awake dogs after laparotomy.
AB  - Pulmonary complications after upper abdominal surgery are usually ascribed to
      temporary postoperative impairment of diaphragm function, which may not originate
      from intrinsic, structural injury but from reflex inhibition of diaphragm
      contractility. Spontaneous breathing is interrupted periodically by sighs, even
      after upper abdominal surgery. If postoperative dysfunction of the diaphragm
      arises from a reflexic inhibition, then the sigh should temporarily override the
      inhibition and restore normal diaphragm function. We implanted sonomicrometer and
      electromyogram transducers chronically in six dogs by laparotomy, then directly
      measured length, shortening, and electromyogram activity of costal and crural
      diaphragm segments, parasternal intercostal, and transversus abdominis muscles an
      average of 8.7 (range, 1-16) d later during resting tidal breathing and sighs. In
      each animal we analyzed a sequence of breaths, including a sigh, when costal or
      crural diaphragm contractility was abnormal. With each sigh, the shape and
      amplitude of costal and crural diaphragm segmental shortening improved abruptly,
      from 0.9 and 1.4% of baseline length (% LBL) during resting breathing to 12.1 and
      11.1% LBL, respectively, during sighs. The sighs were compared to CO2-stimulated
      breaths of equivalent tidal volume, which did not show either pattern or
      amplitude of shortening equivalent to sighs. We conclude that diaphragm
      dysfunction after laparotomy arises from a reflex inhibition, which is overridden
      abruptly to return diaphragm function briefly to normal during each spontaneous
      sigh.

PMID- 9563724
TI  - Do molecular markers predict survival in non-small-cell lung cancer?
AB  - Patients with non-small-cell lung cancer (NSCLC) survive for variable lengths of
      time, even when adjustment is made for pathological stage. Numerous reports
      suggest that biological markers predict survival in patients undergoing surgery
      for NSCLC with curative intent, but many of these claims are unconfirmed or
      conflicting. We postulated that the use of multiple putative markers might
      provide greater power in predicting survival. We studied 101 consecutive patients
      with NSCLC who underwent exploratory thoracotomy and who were followed for at
      least 2 yr. We assessed mutations in the p53 tumor suppressor gene (exons 5-8)
      and the K-ras oncogene (codons 12 and 13) by polymerase chain reaction
      amplification and single strand conformation polymorphism of the product. We
      identified 19 K-ras mutations (all adenocarcinomas except for two) and 40 p53
      mutations among the 101 cases. We also evaluated p53 protein, bcl-2 protein, c
      erbB-1 protein, c-erbB-2 protein, and MIA-15-5 antigen by standard
      immunocytochemical techniques, and we found that all of these antigens were
      variably expressed. As expected, we found a strong inverse association between
      surgical tumor stage and survival. Of the molecular markers studied, only MIA-15
      5 antigen expression correlated strongly with survival by univariate analysis (p
      = 0.001) and it remained a significant predictor by multivariate analysis (p =
      0.01). However, in this study, overexpression of MIA-15-5 antigen predicted an
      improved survival, whereas the original report showed a worse prognosis (N. Engl.
      J. Med. 1992;327:14). We conclude the multiple cell markers are not clinically
      useful in predicting survival among patients undergoing surgery for NSCLC.
      Differences between our results and prior reports may be due to chance, to true
      population differences, or to other factors.

PMID- 9563725
TI  - Blood pressure in children with obstructive sleep apnea.
AB  - Hypertension is a common complication of obstructive sleep apnea in adults.
      However, hypertension has not been studied systematically in children with the
      obstructive sleep apnea syndrome (OSAS). We therefore measured blood pressure
      (BP) during polysomnography in 41 children with OSAS, compared to 26 children
      with primary snoring (PS). Systolic and diastolic BP were measured every 15 min
      via an appropriately sized arm cuff, using an automated system. This was
      tolerated by the children without inducing arousals from sleep. Children with
      OSAS had a significantly higher diastolic BP than those with PS (p < 0.001 for
      sleep and p < 0.005 for wakefulness). There was no significant difference in
      systolic BP between the two groups. Multiple linear regression showed that blood
      pressure could be predicted by apnea index, body mass index, and age. Blood
      pressure during sleep was lower than during wakefulness (p < 0.001 for diastole
      and p < 0.01 for systole), but did not differ significantly between rapid eye
      movement (REM) and non-REM sleep. We conclude that childhood OSAS is associated
      with systemic diastolic hypertension.

PMID- 9563726
TI  - Dipyridamole potentiates pulmonary vasodilation induced by acetylcholine and
      nitric oxide in the ovine fetus.
AB  - Nitric oxide (NO) modulates pulmonary vascular resistance (PVR) in the normal
      fetus by increasing the cyclic guanosine 3',5'-monophosphate (cGMP) content of
      pulmonary vascular smooth muscle cells. Although several vasodilator stimuli,
      including acetylcholine, decrease fetal PVR through the release of endogenous NO,
      fetal pulmonary vasodilation is often transient despite prolonged treatment.
      Because cGMP is hydrolyzed and inactivated by cGMP-specific (type 5)
      phosphodiesterases (PDE5), we hypothesized that PDE5 activity contributes to high
      fetal PVR and limits the capability of the fetal pulmonary circulation to dilate
      or sustain vasodilation in response to cGMP-dependent stimuli. To test this
      hypothesis, we studied the hemodynamic effects of dipyridamole in 19 late
      gestation fetal lambs. To determine whether dipyridamole-induced vasodilation is
      dependent upon basal NO release, we measured the response to dipyridamole before
      and after pretreatment with the NO synthase antagonist nitro-L-arginine (L-NA) in
      five fetal lambs. L-NA completely blocked dipyridamole-induced pulmonary
      vasodilation. To evaluate the effect of dipyridamole on pulmonary vasodilation
      due to the stimulated release of NO, we studied effects of prolonged
      intrapulmonary acetylcholine infusions, with and without concomitant
      administration of low-dose dipyridamole, in six fetal lambs. During prolonged (2
      h) infusions, acetylcholine and dipyridamole individually caused transient
      pulmonary vasodilation. When administered together, pulmonary vasodilation was of
      greater magnitude and was sustained for the entire study period. To determine the
      effects of dipyridamole on endothelium-independent pulmonary vasodilation, we
      investigated the hemodynamic effects of inhaled NO (5 and 20 ppm) alone and in
      combination with dipyridamole during mechanical ventilation with low FlO2. The
      combination of dipyridamole with inhaled NO resulted in a greater degree of
      pulmonary vasodilation than that achieved with inhaled NO alone. We conclude that
      dipyridamole-induced pulmonary vasodilation is dependent on endogenous (basal) NO
      production and that dipyridamole potentiates vasodilator responses to endothelium
      dependent and -independent dilators in the ovine fetal pulmonary circulation. We
      speculate that PDES activity opposes vasodilation and maintains high PVR in the
      normal fetal lung.

PMID- 9563727
TI  - Effect of dexfenfluramine treatment in rats exposed to acute and chronic hypoxia.
AB  - The anorexiant dexfenfluramine, which inhibits 5-hydroxytryptamine (5-HT) uptake,
      has been associated with an increase in the relative risk of developing primary
      pulmonary hypertension. The aim of this study was to investigate in rats whether
      dexfenfluramine (1) alters the pulmonary vasomotor effects of 5-HT and (2)
      aggravates the development of pulmonary hypertension during exposure to various
      levels of chronic hypoxia. In isolated lungs from normoxic rats, dexfenfluramine
      up to 10(-4) M did not elicit any vasoactive effects, and neither did
      pretreatment with dexfenfluramine (10[-5] M in the perfusate) modify the
      vasoactive effects of 5-HT. In normoxic conscious rats, dexfenfluramine given
      intravenously potentiated the pulmonary pressor response to acute hypoxia (10%
      O2). In rats chronically treated with dexfenfluramine during a 2-wk exposure to
      15% or 10% O2, plasma 5-HT concentrations were significantly increased compared
      with hypoxic controls, whereas no differences were found for pulmonary artery
      pressure, right ventricular hypertrophy, or pulmonary vessel muscularization. In
      contrast, a continuous 5-HT infusion providing a sustained increase in plasma 5
      HT levels was associated with increased muscularization of distal pulmonary
      arteries in response to 10% O2. Simultaneous administration of dexfenfluramine
      prevented the effect of exogenous 5-HT on vascular remodeling. Our findings show
      that dexfenfluramine does not potentiate the development of pulmonary
      hypertension in rats exposed to chronic hypoxia, despite its effect on plasma 5
      HT concentrations.

PMID- 9563728
TI  - Alveolar macrophages from atopic asthmatics, but not atopic nonasthmatics,
      enhance interleukin-5 production by CD4+ T cells.
AB  - Recent studies have demonstrated that different antigen-presenting cell (APC)
      related factors in the microenvironment of a T cell may determine its profile and
      quantity of cytokine expression and production. We have therefore examined the
      effects of alveolar macrophages and peripheral blood monocytes on interleukin
      (IL)-5 production by peripheral blood CD4+ T cells from atopic people with asthma
      (AA), atopic people without asthma (AN), and nonatopic normal subjects (N). In
      response to allergen stimulation, IL-5 production was significantly enhanced by
      the addition of monocytes to CD4+ cell cultures in AA and AN patients (p < 0.05
      and 0.01, respectively), but not in N subjects. In mitogen-stimulated CD4+ cell
      plus monocyte cocultures, there was a small increase in IL-5 production in all
      three groups (p < 0.05 for AN). In contrast, the addition of alveolar macrophages
      to parallel cultures significantly amplified IL-5 production only in AA patients
      (p < 0.05 or 0.01). Furthermore, IL-5 production by CD4+ cells in alveolar
      macrophage cocultures, stimulated by allergen or mitogen, was higher than that in
      monocyte cocultures in AA patients (p < 0.05). Conversely, in AN and N subjects,
      the IL-5 values for alveolar macrophage cocultures were lower than those for
      peripheral blood monocytes. In blocking studies, antibodies against IL-1alpha, IL
      1beta, IL-6, or tumor necrosis factor-alpha differentially suppressed macrophage
      enhanced IL-5 production (p < 0.05 for IL-1beta and IL-6) and expression of the
      activation marker CD25 (p < 0.05 for IL-1alpha and IL-6) by allergen-stimulated
      CD4+ cells in AA patients. These observations suggest that alveolar macrophages
      influence the quantity of IL-5 production by T cells in the airways and, as a
      consequence, the development of asthma in atopic individuals.

PMID- 9563729
TI  - Safety of inducing sputum in patients with asthma of varying severity.
AB  - Inducing sputum using hypertonic saline is a noninvasive method to investigate
      airway inflammation in people with asthma. However, hypertonic saline may also
      induce bronchoconstriction in some patients. The aim of the study was to examine
      whether the overall safety of using hypertonic saline to induce sputum in
      patients with mild to moderate asthma could be extended to patients with severe
      and/or uncontrolled asthma. Nine control subjects and 64 asthmatic patients with
      varying severity of the disease (FEV1 40-126% predicted values) were studied.
      Twenty-one of those patients had uncontrolled asthma. Sputum was induced in a
      standardized manner using hypertonic saline. The safety of the procedure was
      evaluated by assessing the clinical response and measuring FEV1 just before and
      during sputum induction. The procedure was well tolerated in most patients, but
      it had to be stopped due to side effects in 11.6% of patients with severe asthma.
      None of the side reactions were severe. Few patients with uncontrolled (17.3%) or
      severe asthma (18.6%) had a drop in FEV1 of 10-20%. The fall in FEV1 was
      significantly greater in patients with severe asthma than those with mild disease
      (p < 0.02 Mann-Whitney U test). We conclude that hypertonic saline-induced sputum
      is a safe technique even in patients with severe asthma.

PMID- 9563730
TI  - Unplanned extubations in the adult intensive care unit: a prospective multicenter
      study. Association des Reanimateurs du Centre-Ouest.
AB  - The predisposing factors and complications of unplanned extubation (UEX) in
      mechanically ventilated adult patients are not well recognized. We designed a
      prospective multicenter observational study to identify risk factors and describe
      the complications of UEX. We followed 426 ventilated patients over a 2-mo period.
      Clinical characteristics such as diagnosis on admission and reasons for
      ventilation were used to classify the patients. The presence or absence of
      potential risk factors was daily noted, including the types of ventilators,
      tracheal tubes, tube fixations, ventilatory support modes, route for intubation,
      and the use of intravenous sedation. Circumstances and complications of UEX were
      prospectively recorded. Forty-six (10.8%) patients experienced at least one
      episode of UEX. Ten UEX occurred during nursing procedures. At the moment of UEX,
      61% of patients were agitated. The rates of mortality, laryngeal complications,
      nosocomial pneumonia after extubation, and the length of mechanical ventilation
      were similar in UEX and non-UEX patients. Patients were more often reintubated
      after UEX (28 of 46) than after planned extubation (28 of 284). All the non
      reintubated UEX patients survived. One death occurred as a direct consequence of
      UEX. By use of multivariate analysis, we identified four factors contributing to
      UEX: chronic respiratory failure, endotracheal tube fixation with only thin
      adhesive tape, orotracheal intubation, and the lack of intravenous sedation.
      Considering these factors, we hypothesized that simple measures should be adopted
      to minimize the incidence of UEX and its related complications: more vigilance
      during procedures at patients' bedsides, adequate sedation of agitated patients,
      strong fixation of the tracheal tube, particular attention paid to orally
      intubated patients, and daily reassessment of the possibility of weaning from the
      ventilator.

PMID- 9563731
TI  - Diesel exhaust enhances allergic airway inflammation and hyperresponsiveness in
      mice.
AB  - We previously reported that the intratracheal instillation of diesel exhaust
      particles enhances allergic airway inflammation and hyperresponsiveness in mice.
      However, it is not known whether the effects of such instillation differ from
      those obtained with the daily inhalation of diesel exhaust. We therefore examined
      whether the inhalation of diesel exhaust would also enhance allergic reactions.
      Mice were exposed to diesel exhaust or clean air for 5 wk. After the first week,
      the animals were sensitized to ovalbumin by intraperitoneal injection. At the end
      of the exposure period, they underwent an ovalbumin challenge. Control animals
      received saline instead of ovalbumin. Independently of ovalbumin sensitization,
      diesel exhaust caused an increase in the numbers of neutrophils and macrophages
      in bronchoalveolar lavage fluid, whereas a significant increase in eosinophil
      numbers occurred only after antigen challenge combined with diesel exhaust
      exposure. Furthermore, ovalbumin alone caused an increase in eosinophil numbers
      in lung tissue, and this was enhanced by diesel exhaust. Exposure to diesel
      exhaust combined with ovalbumin sensitization, but not diesel exhaust inhalation
      alone, enhanced the number of goblet cells in lung tissue, respiratory
      resistance, production of ovalbumin-specific immunoglobulin E and G1 in the
      serum, and expression of interleukin-5 in lung tissue.

PMID- 9563732
TI  - Determinants of aerobic and anaerobic exercise performance in cystic fibrosis.
AB  - We examined aerobic and anaerobic exercise performance in 17 subjects with cystic
      fibrosis (CF) (age 25+/-10 [SD] yr; 47% females; FEV1 62+/-21% pred) and 17 age-
      and sex-matched control subjects (age 25+/-8 [SD] yr; 41% females; FEV1 112+/-15%
      pred) in relation to pulmonary function and nutritional status. Aerobic capacity
      was determined as maximal oxygen consumption (VO2max) (ml/kg/min) and anaerobic
      threshold (AT; ml VO2/kg/min) from a graded exercise stress test on an
      electronically braked bicycle ergometer. Anaerobic performance was assessed from
      the average work of two bouts of pedaling to exhaustion at a load corresponding
      to 130% Vo2max from graded exercise. Both aerobic and anaerobic performances were
      decreased in subjects with CF (p < 0.001). The duration of anaerobic exercise in
      subjects with CF was similar to control subjects. In control subjects, pulmonary
      function did not correlate to aerobic or anaerobic exercise. In subjects with CF
      significant relationships between FEV1, vital capacity, and FEF25-75% to AT were
      found, suggesting the pulmonary limitation to aerobic capacity. In both patients
      with CF and control subjects, lean body mass and arm muscle area significantly
      correlated with anaerobic performance but not with VO2max or AT. We conclude that
      nutritional status, rather than pulmonary function, is the major determinant of
      anaerobic exercise capacity in CF. The preserved duration of anaerobic exercise
      at equivalent workloads (corresponding to 130% of VO2max from graded exercise)
      suggests that readily available energy stores in muscle may be similar in CF and
      normal individuals.

PMID- 9563734
TI  - Acute lung injury in the medical ICU: comorbid conditions, age, etiology, and
      hospital outcome.
AB  - The independent effects of chronic disease, age, severity of illness, lung injury
      score (LIS) and etiology, and preceding nonpulmonary organ-system dysfunction
      (OSD) on the outcome of acute lung injury (ALI) have not been examined in an
      exclusively medical-intensive-care-unit (MICU) population. Therefore, 107
      consecutive MICU patients with ALI (76% with acute respiratory distress syndrome
      [ARDS]) were prospectively investigated. The impact of comorbidities, age > 65
      yr, acute physiology score (APS), LIS, etiology of ALI, and OSD on hospital
      survival were studied. The overall mortality was 62 of 107 patients (58%),
      including 47 (58%) with ARDS. With univariate analysis, age > 65 yr, organ
      transplantation, human immunodeficiency virus (HIV) infection, active malignancy,
      chronic steroid use, and a septic or aspiration-related etiology of ALI were
      associated with a > or = 1.2-fold greater relative risk (RR) of hospital
      mortality. With multiple logistic regression, independent predictors of hospital
      death were age > 65 yr, organ transplantation, HIV infection, cirrhosis, active
      malignancy, and sepsis. APS, LIS, aspiration-related etiology of ALI, preceding
      OSD, and other comorbidities were not independently predictive of hospital death.
      Multivariate analysis of the ARDS cohort showed similar results, although
      cirrhosis and malignancy did not reach statistical significance. We conclude that
      comorbid conditions, older age, and sepsis etiology are independent predictors of
      hospital death in exclusively MICU patients with ALI (76% of whom satisfied
      criteria for ARDS). These factors should be considered in analyzing studies of
      new therapies and interpreting trends in mortality for ALI and ARDS.

PMID- 9563733
TI  - Risk factors and outcome of nosocomial infections: results of a matched case
      control study of ICU patients.
AB  - Intensive-care-unit (ICU) patients are at risk for both acquiring nosocomial
      infection and dying, and require a high level of therapy whether infection occurs
      or not. The objective of the present study was to precisely define the
      interrelationships between underlying disease, severity of illness, therapeutic
      activity, and nosocomial infections in ICU patients, and their respective
      influences on these patients' outcome. In a 10-bed medical ICU, we conducted a
      case-control study with matching for initial severity of illness, with daily
      monitoring of severity of illness and therapeutic activity scores, and with
      analysis of the contribution of nosocomial infections to patients' outcomes.
      Forty-one cases of patients who developed nosocomial infections during a 1-yr
      period were paired with 41 controls without nosocomial infection according to
      three criteria: age (+/- 5 yr), Acute Physiology and Chronic Health Evaluation II
      (APACHE II) score (+/- 5 points), and duration of exposure to risk. Successful
      matching was achieved for 118 of 123 (96%) variables. Neurologic failure on the
      third day after ICU admission was the sole independent risk factor for nosocomial
      infection (adjusted odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.09 to
      1.64; p = 0.007). Unlike control patients, case patients showed no clinical
      improvement and required a high level of therapeutic activity between ICU
      admission and the day of infection. Mortality attributable to nosocomial
      infection was 44%. Excess length of stay and duration of antibiotic treatment
      attributable to nosocomial infection were 14 d and 10 d, respectively.
      Attributable therapeutic activity as measured with the Therapeutic Intervention
      Scoring System (TISS) and Omega score was 368 and 233 points, respectively. Such
      consequences were observed in patients who developed multiple infections. These
      findings suggest that a persistent high level of therapeutic activity and
      persistent impaired consciousness are risk factors for nosocomial infections in
      ICU patients. These infections are responsible for excess mortality, prolongation
      of stay, and excess therapeutic activity resulting in important cost overruns for
      health-care systems.

PMID- 9563735
TI  - Nosocomial pneumonia in patients with acute respiratory distress syndrome.
AB  - To describe the epidemiologic and microbial aspects of ventilator-associated
      pneumonia (VAP) in patients with acute respiratory distress syndrome (ARDS), we
      prospectively evaluated 243 consecutive patients who required mechanical
      ventilation (MV) for > or = 48 h, 56 of whom developed ARDS as defined by a
      Murray lung injury score > 2.5. We did this with bronchoscopic techniques when
      VAP was clinically suspected, before any modification of existing antimicrobial
      therapy. For all patients, the diagnosis of pneumonia was established on the
      basis of culture results of protected-specimen brush (PSB) (> or = 10(3) cfu/ml)
      and bronchoalvelolar lavage fluid (BALF) (> or = 10(4) cfu/ml) specimens, and
      direct examination of cells recovered by bronchoalveolar lavage (BAL) (< or = 5%
      of infected cells). Thirty-one (55%) of the 56 patients with ARDS developed VAP
      for a total of 41 episodes, as compared with only 53 (28%) of the 187 patients
      without ARDS for a total of 65 episodes (p = 0.0005). Only 10% of first episodes
      of VAP in patients with ARDS occurred before Day 7 of MV, as compared with 40% of
      the episodes in patients without ARDS (p = 0.005). All but two patients with ARDS
      who developed VAP had received antimicrobial treatment (mostly with broad
      spectrum antibiotics) before the onset of infection, as compared with only 35
      patients without ARDS (p = 0.004). The organisms most frequently isolated from
      patients with ARDS and VAP were methicillin-resistant Staphylococcus aureus
      (23%), nonfermenting gram-negative bacilli (21%), and Enterobacteriaceae (21%).
      These findings confirm that microbiologically provable VAP occurs far more often
      in patients with ARDS than in other ventilated patients. Because these patients
      are often treated with antibiotics early in the course of the syndrome, the onset
      of VAP is frequently delayed after the first week of MV, and is then caused
      mainly by methicillin-resistant S. aureus and other multiresistant
      microorganisms.

PMID- 9563736
TI  - Computer-based models to identify high-risk children with asthma.
AB  - Effective management of populations with asthma requires methods for identifying
      patients at high risk for adverse outcomes. The aim of this study was to develop
      and validate prediction models that used computerized utilization data from a
      large health-maintenance organization (HMO) to predict asthma-related
      hospitalization and emergency department (ED) visits. In this retrospective
      cohort design with split-sample validation, variables from the baseline year were
      used to predict asthma-related adverse outcomes during the follow-up year for
      16,520 children with asthma-related utilization. In proportional-hazard models,
      having filled an oral steroid prescription (relative risk [RR]: 1.9; 95%
      confidence interval [CI]: 1.3 to 2.8) or having been hospitalized (RR: 1.7; 95%
      CI: 1.1 to 2.7) during the prior 6 mo, and not having a personal physician listed
      on the computer (RR: 1.6; 95% CI: 1.1 to 2.3) were associated with increased risk
      of future hospitalization. Classification trees identified previous
      hospitalization and ED visits, six or more beta-agonist inhalers (units) during
      the prior 6 mo, and three or more physicians prescribing asthma medications
      during the prior 6 mo as predictors. The classification trees performed similarly
      to proportional-hazards models, and identified patients who had a threefold
      greater risk of hospitalization and a twofold greater risk of ED visits than the
      average patient. We conclude that computer-based prediction models can identify
      children at high risk for adverse asthma outcomes, and may be useful in
      population-based efforts to improve asthma management.

PMID- 9563737
TI  - Red-blood-cell augmentation of hypoxic pulmonary vasoconstriction: hematocrit
      dependence and the importance of nitric oxide.
AB  - Red blood cells (RBCs) are known to augment hypoxic pulmonary vasoconstriction
      (HPV). To determine whether this phenomenon is hematocrit (Hct) dependent and
      related to alterations of either nitric oxide (NO) or adenosine metabolism, we
      studied mechanically ventilated, pump-perfused lungs from euthanized New Zealand
      White rabbits. Lungs were perfused in situ in a recirculating manner at constant
      flow; perfusates consisted of Krebs-Henseleit buffer or buffer plus washed RBCs
      at a Hct of 10% or 30%. HPV was quantitated as the increase in pulmonary artery
      pressure (Ppa) from baseline after 5 min of hypoxia. In three experimental sets,
      we studied the effects of Hct on HPV and expired NO, the effects of nitric oxide
      synthase (NOS) inhibition, and the effects of adenosine receptor blockade. HPV
      was greater at a higher Hct, and expired NO varied inversely with Hct and
      decreased with hypoxia. NOS inhibition eliminated RBC-dependence of HPV.
      Adenosine-receptor blockade did not affect the RBC-dependence of HPV. We conclude
      that HPV is dependent on Hct, and that this phenomenon may be related to
      scavenging of NO but not adenosine by RBCs.

PMID- 9563738
TI  - Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional
      therapy in aspirin-intolerant asthmatics.
AB  - From bronchoprovocation studies and investigations of the acute effects of drugs
      that inhibit leukotrienes (LT), the hypothesis has emerged that leukotrienes are
      important mediators of airway obstruction and other symptoms in aspirin
      intolerant asthma (AIA). However, it has yet not been shown if subjects with AIA
      respond favorably to clinical treatment with leukotriene inhibitors. Therefore,
      in a double-blind placebo-controlled crossover study, we examined the effects of
      6 wk of treatment with the leukotriene-pathway inhibitor zileuton (600 mg, four
      times daily) in 40 patients with well-characterized AIA. The treatment was added
      to existing therapy, which included medium to high doses of inhaled (average
      daily dose 1,030 microg of beclomethasone or budesonide) or oral
      glucocorticosteroids (4 to 25 mg/d) for all but one of the patients. On top of
      this treated baseline, there were no significant effects of adding placebo,
      indicating that their asthma was kept relatively stable. However, there was an
      acute and chronic improvement in pulmonary function after treatment with
      zileuton, expressed both as increased FEV1 from baseline compared with placebo,
      and higher morning and evening peak expiratory flow rate (PEFR) values on
      zileuton treatment compared with placebo. The improvements occurred despite lower
      use of rescue bronchodilator with zileuton. Zileuton also diminished nasal
      dysfunction, which is one of the cardinal signs of AIA. There was a remarkable
      return of smell, less rhinorrhea, and a trend for less stuffiness and higher
      nasal inspiratory flow during treatment with zileuton. Zileuton caused a small
      but distinct reduction of bronchial hyperresponsiveness to histamine and
      inhibited aspirin-induced bronchoconstriction. Zileuton inhibited urinary
      excretion of LTE4 but did not change airway reactivity to inhaled LTD4,
      supporting that zileuton specifically inhibited leukotriene biosynthesis. The
      findings indicate that leukotrienes are important mediators of persistent airway
      obstruction and chronic nasal dysfunction in AIA. The study also suggests that
      addition of a leukotriene pathway inhibitor such as zileuton may bring about
      greater control of asthma than what is achieved by treatment with medium to high
      doses of glucocorticosteroids alone.

PMID- 9563739
TI  - Improved exercise performance following lung volume reduction surgery for
      emphysema.
AB  - Lung volume reduction surgery (LVRS) for emphysema has been suggested to improve
      patient lung function and activity. The short-term impact of LVRS on exercise
      performance was evaluated using maximal and submaximal steady-state exercise
      testing in 27 patients with severe hypoxemic chronic obstructive pulmonary
      disease (COPD), along with measurements of patient function, dyspnea, and quality
      of life. LVRS significantly improved exercise performance, due to ventilatory
      improvements associated with increased ventilatory reserve, enhanced tidal volume
      recruitment, and improved alveolar ventilation. Preoperative measurements of
      ventilatory reserve and dead space ventilation during exercise testing were
      closely associated with improved exercise performance. Improvements in patient
      dyspnea, walk distances, and quality of life also occurred following LVRS and
      were associated with improvements in exercise performance. Surgical mortality
      from LVRS was low (4%), but short-term all-cause mortality was increased (19%).
      Short-term mortality was associated with reduced expiratory muscle strength and
      markedly elevated dead space ventilation. We conclude that LVRS produces
      significant improvements in exercise performance, dyspnea, and quality of life in
      selected patients with COPD. Physiologic prediction of patients most likely to
      survive for an extended period and have significant benefit following LVRS may
      also be possible.

PMID- 9563740
TI  - Comparison of static mechanical properties of the passive pharynx between normal
      children and children with sleep-disordered breathing.
AB  - Collapsibility of the active pharynx, where active contraction of the upper
      airway muscles is evident, was previously reported to be higher in children with
      obstructive sleep apnea (OSA) than in those with primary snoring during sleep.
      Contribution of neuromuscular and anatomic factors to the increased
      collapsibility, however, was not estimated. We therefore evaluated collapsibility
      of the passive pharynx, in which upper airway muscle activities were eliminated.
      Our aim in the present study was to test the hypothesis that children with sleep
      disordered breathing (SDB) have a structurally narrowed and a more collapsible
      pharynx compared with normal children. The static pressure/area relationship of
      the passive pharynx was endoscopically quantified in 14 children with SDB and in
      13 normal children under general anesthesia with complete paralysis. The majority
      of children with SDB primarily closed their airways at levels of enlarged
      adenoids and tonsils with positive closing pressure (Pclose) (3.5+/-4.3 cm H2O),
      whereas half of the normal children closed their airways at the soft palate edges
      and the other half at the tongue bases with subatmospheric Pclose (-7.4+/-4.9 cm
      H2O). Cross-sectional area of the narrowest segment was significantly smaller in
      SDB children than in normal children. Interestingly, collapsibility of the
      retropalatal and retroglossal segments significantly increased in SDB children,
      compared with the normal subjects. We conclude that anatomic factors play a
      significant role in the pathogenesis of pediatric OSA and that predisposing
      structural abnormalities of the entire pharynx are likely to contribute to
      manifestation of OSA in addition to enlarged adenoids and tonsils.

PMID- 9563741
TI  - Effects of mean airway pressure on lung volume during high-frequency oscillatory
      ventilation of preterm infants.
AB  - Measurement of mean lung volume (MLV) in high-frequency oscillatory ventilation
      (HFO) may be useful for optimizing the high lung volume strategy, but has not
      been available until now. We have measured MLV by means of the sulfur
      hexafluoride (SF6) washout method in 13 premature infants ventilated with HFO
      because of respiratory distress syndrome (gestational age, 23 to 31 wk [median,
      25 + 6/7 wk]; birthweight, 630 to 1,140 g [790 g]; age at measurement, 2 to 10 d
      [4 d]; weight, 675 to 1,250 g [850 g]). To evaluate the relationship between MLV
      and mean airway pressure (MAP), the latter was systematically varied between the
      measurements. With clinically selected MAP, MLV was between 23.3 and 41.9 ml/kg
      (median, 33.5 ml/kg) and was strongly dependent on MAP in each patient; linear
      regression analyses resulted in slope factors between 1.0 and 6.9 ml/cm H2O/kg
      (median, 2.83 ml/cm H2O/kg), with correlation coefficients between 0.77 and 0.99
      (median, 0.94). Stabilization of MLV after modification of MAP took 2 to 25 min
      (median, 9 min). We conclude that the selection of MAP on a clinical basis leads
      to a wide range of different MLVs. Despite the strong dependence of MLV on MAP,
      the prediction of MLV solely based on MAP was impossible because of large patient
      to patient variability of linear regressions. Alveolar recruitment and
      derecruitment may take up to 25 min after MAP changes.

PMID- 9563742
TI  - Does hepato-splanchnic VO2/DO2 dependency exist in critically ill septic
      patients?
AB  - Since the gradient between the mixed venous and hepatic vein oxygen saturation
      (DSO2) is often increased in septic patients, we suspected these patients may
      have an imbalance between oxygen supply and demand in the hepato-splanchnic area.
      In 42 septic patients, hepato-splanchnic blood flow was determined by the
      indocyanine green clearance method with hepatic vein catheterization. The
      relationships between hepato-splanchnic oxygen delivery (DO2spla) and consumption
      (VO2spla) were analyzed during an increase in blood flow induced by a dobutamine
      infusion at doses up to 10 microg/kg x min. In 14 patients, positive end
      expiratory pressure (PEEP) was also increased up to 20 cm H2O. The patients were
      separated according to their DSO2 (Group I: DSO2 < 10%, n = 13; and Group II:
      DSO2 > 10%, n = 29). Although DO2spla increased similarly in both groups, VO2spla
      only increased in Group II (from 45+/-22 to 59+/-39 ml/min x M2, p < 0.01). The
      slope of the VO2spla/DO2spla relationship was higher in Group II than in Group I
      (31.2+/-16.7 versus 10.4+/-5.1%, p < 0.001) and was similar during dobutamine and
      PEEP (21.9+/-14.2 versus 21.9+/-14.0%, p = NS). In conclusion, VO2spla increased
      only in septic patients with an increased DSO2 indicating splanchnic dysoxia. The
      similar slope observed with dobutamine and PEEP suggests that a thermogenic
      effect was unlikely.

PMID- 9563744
TI  - Circulating adhesion molecules in cystic fibrosis.
AB  - A marked influx of inflammatory cells occurs into the airways of patients with
      cystic fibrosis (CF), which may contribute to the development of lung injury.
      Leukocyte-endothelial adhesion molecules play a crucial role in the recruitment
      of inflammatory cells, and soluble forms of these molecules have been shown to
      increase in several inflammatory diseases. By using a capture ELISA, we
      determined serum levels of soluble ICAM-1 (sICAM-1), E-selectin (sE-selectin),
      and VCAM-1 (sVCAM-1) in patients with CF, in stable clinical conditions (n = 29,
      mean age: 25.8+/-1.5 yr), and healthy control subjects (n = 12, mean age: 27.6+/
      1.5 yr). Clinical, spirometric, microbiological, and hematological assessments
      were made in all subjects. sICAM-1 and sE-selectin concentrations, but not sVCAM
      1 levels were significantly increased in CF patients as compared with normal
      subjects (both p < 0.001). sICAM-1 levels were inversely related to FEV1 values
      (r = -0.519, p = 0.004) and Schwachman score (r = -0.405, p = 0.03) in CF
      patients. In 7 of 29 CF patients, soluble adhesion molecule levels were
      determined not only at the time of stable clinical conditions, but also before
      and after antibiotic treatment for a pulmonary exacerbation. sICAM-1 and sE
      selectin levels increased in all patients at the time of the exacerbation,
      compared with levels at the time of stable conditions (p < 0.02 for both
      comparisons); antibiotic treatment induced a significant decrease of both
      circulating adhesion molecules (p < 0.02). The elevated serum levels of sICAM-1
      and sE-selectin in CF patients, even when they are clinically stable, may reflect
      the marked and persistent inflammatory process in the disease.

PMID- 9563743
TI  - Longitudinal estimates of pulmonary function in refractory ceramic fiber
      manufacturing workers.
AB  - Refractory ceramic fibers (RCF) are man-made vitreous fibers (MMVF) used in high
      temperature industrial applications. Between 1987 and 1994, a prospective study
      evaluated pulmonary function of 361 male workers currently employed in RCF
      manufacturing and related operations for plausibility of a causal relationship
      between RCF exposure and pulmonary function changes. Workers included in the
      analysis provided at least five pulmonary function tests. The exposure-response
      relationship was modeled with two exposure variables: years in a production job,
      and cumulative fiber exposure (fiber-mo/cc). Comparison groups were nonproduction
      workers and workers with up to 15 fiber-mo/cc cumulative exposure. A
      statistically significant decrease in FVC was demonstrated among workers employed
      in production jobs more than 7 yr prior to initial test. A similar but
      nonstatistically significant result was demonstrated for FVC in workers with
      greater than 60 fiber-mo/cc cumulative exposure prior to initial pulmonary
      function test. Similar but nonstatistically significant results were obtained for
      FEV1. These findings, which primarily reflect workers employed before 1980, did
      not persist with analysis of follow-up production years and accumulated RCF
      exposure from initial pulmonary function test. Since longitudinal analyses are
      sensitive to influences that continue to affect annual decline during the study
      period, lower RCF exposure levels since the 1980s may be responsible for
      eliminating any further effect on pulmonary function.

PMID- 9563745
TI  - Quality assessment of protected specimen brush samples by microscopic cell count.
AB  - Protected specimen brushing (PSB), combined with quantitative culture, is now
      recognized as one of the reference methods for diagnosis of nosocomial pneumonia.
      However, no criteria exist with which to assess the quality of the PSB sample. We
      studied numbers of inflammatory cells and bronchial cells per microscopic field
      (magnification: x500, objective x50) in cytospin preparations of PSB samples.
      Results of cell count and quantitative culture in a first study period were
      compared with those in a second study period, following adaptation of the PSB
      technique and collection of samples from more peripheral sites. The cellular
      content of samples from patients and controls was investigated. We examined 86
      samples from patients with suspected nosocomial pneumonia and 15 samples from
      uninfected controls. The number of samples with a high cellular content was
      considerably greater in the second study period. No positive cultures were
      obtained from samples containing < 10 cells per field. The numbers of cells in
      samples from uninfected controls were comparable to the numbers in samples from
      patients. Our results indicate that absence of cells probably represents
      inadequate sampling. Negative PSB cultures with cytospin preparations containing
      < 10 cells per microscopic field should therefore be considered with caution, and
      resampling considered.

PMID- 9563746
TI  - Why do symptomatic patients delay obtaining care for tuberculosis?
AB  - The resurgence of tuberculosis (TB) has coincided with deteriorating access to
      care for high-risk populations. We sought to determine what perceived access
      barriers delayed symptomatic TB patients from obtaining care. In order to do
      this, we conducted a survey in Los Angeles County, California, using a
      consecutive sample of patients with active TB as confirmed by the county TB
      control authority. The measures used in the study were a self-reported delay in
      seeking care of more than 60 d from symptom onset, a period sufficient to cause
      skin-test conversion in exposed contacts, and self-reported access barriers. The
      county TB registry provided supplementary clinical data. We found that one in
      five of the 248 symptomatic respondents (response rate: 60%) delayed obtaining
      care for > 60 d (mean = 74 d, SD = 216 d). During the delay, patients exposed an
      average of eight contacts. As compared with the rest of the sample, delay was
      more common in those who were unemployed (25% versus 14%), concerned about cost
      (27% versus 14%), anticipated prolonged waiting-room time (26% versus 14%),
      believed they could treat themselves (31% versus 14%), anticipated difficulty in
      getting an appointment (28% versus 16%), were uncertain about where to get care
      (33% versus 16%), and feared immigration authorities (47% versus 18%) (p < 0.05).
      Logistic regression revealed that uncertainty about where to get care,
      unemployment, and belief in the efficacy of self-treatment independently
      predicted delay > 60 d. Illness severity as measured by chest radiography, sputum
      smears, and symptoms had little impact on delay. We conclude that because access
      variables such as lack of employment and knowledge about where to obtain care
      were more closely associated with clinically significant delay than was severity
      of illness, these results raise concerns about the equity of access to care among
      TB patients. The results suggest that improving the availability of services for
      high-risk groups may substantially reduce TB patients' delay in obtaining care,
      and thus may limit the spread of the disease.

PMID- 9563747
TI  - Movement of tuberculosis patients and the failure to complete antituberculosis
      treatment.
AB  - The outcomes of tuberculosis (TB) patients who move before completing
      antituberculosis treatment have not been described. We studied a population-based
      cohort of 2,576 adult patients reported as having TB in California during 1993,
      including 147 patients who moved from one local health jurisdiction to another
      within California. We determined treatment outcomes (completed, defaulted, died,
      other) for 131 (89%) of these 147 patients. Patients who moved defaulted more
      often (relative risk [RR] = 5.5, 95% confidence interval [CI] = 4.1 to 7.4) than
      patients who did not move. Including these patients' treatment outcomes increased
      the known number of defaulters by 30%, from 141 to 183 persons. Additionally,
      diagnosis of TB in a state prison emerged as the strongest risk factor for
      defaulting from treatment. Patients who moved or defaulted were more likely to
      abuse drugs or alcohol, to be homeless or to be associated with congregate
      settings such as jails and prisons. On average, patients who defaulted after
      moving received less than three-quarters of their recommended treatment regimens.
      These patients may remain infectious or become infectious again. Our findings
      highlight the importance of ensuring complete treatment for TB patients who move;
      failure to do so will adversely affect patient health and TB control, especially
      in many high-risk populations and settings.

PMID- 9563748
TI  - Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas
      aeruginosa.
AB  - The present study was aimed at investigating the innate susceptibility of C57BL/6
      Cftrunc/Cftrunc knockout [B6-Cftr (-/-)] mice to pulmonary infection with
      Pseudomonas aeruginosa. Our results indicate that 58.4% of B6-Cftr (-/-) mice
      died within 6 d following lung infection with 10(5) P. aeruginosa entrapped in
      agar beads, whereas only 12.1% of B6-Cftr (+/+) mice died over the same period of
      time. Moreover, the number of bacteria recovered from the lungs of B6-Cftr (-/-)
      mice 3 and 6 d after infection was significantly higher than that observed in
      their littermate controls. No correlation was found between the weight or age of
      the animals and the number of viable bacteria recovered from the lungs of mice.
      Histopathological examination of lung sections from P. aeruginosa-infected mice
      revealed that the infection results in a severe bronchopneumonia. Both B6-Cftr (
      /-) knockout mice and their littermate controls developed similar lung pathology
      during the course of infection. Overall, results reported in the present study
      suggest that a defect at the Cftr locus leads to an exacerbation of P. aeruginosa
      lung infection resulting in a dramatically increased mortality rate and higher
      bacterial load.

PMID- 9563749
TI  - Amiloride analogs inhibit chronic hypoxic pulmonary hypertension.
AB  - Na+/H+ exchange regulation of intracellular pH may play a permissive role in
      pulmonary artery smooth muscle cell (PASM) proliferation. Our laboratory has
      demonstrated that dimethyl amiloride (DMA), an amiloride derivative with enhanced
      selectivity as an inhibitor of the Na+/H+ antiporter, can inhibit bovine PASM
      proliferation in vitro. We hypothesized that DMA would inhibit development of
      hypoxic pulmonary hypertension by interfering with PASM growth in vivo. Sprague
      Dawley rats were exposed to 10% O2 for 14 d without (n 9) or with (n = 7) DMA
      continuous infusion 3 mg/ kg/d. The animals treated with DMA had significant
      reductions in pulmonary artery pressure and total pulmonary vascular resistance
      index (TPVRI) when compared with hypoxic control rats (p < 0.05). Pulmonary
      vascular remodeling was significantly reduced in animals treated with DMA as
      measured by percent wall thickness and percentage of thick-walled intra-acinous
      vessels (p < 0.05). We used a second Na+/H+ exchange inhibitor, ethylisopropyl
      amiloride (EIPA, 3 mg/kg/d, n = 9), and found similar reductions in pulmonary
      artery pressure, TPVRI, and pulmonary vascular remodeling. Polycythemia during
      hypoxia was unchanged by treatment with DMA or EIPA. In conclusion, despite the
      hypertensive effects of polycythemia, DMA and EIPA can significantly reduce
      pulmonary vascular remodeling induced by chronic hypoxia.

PMID- 9563750
TI  - Allergenic activity of a major grass pollen allergen is elevated in the presence
      of nasal secretion.
AB  - Phl p5 is a major allergen of timothy grass and causes rhinitis and bronchial
      asthma in nearly all patients allergic to grass pollen. The biochemical
      processing of this molecule by the nasal mucosa at its first encounter and
      possible changes of its biologic activity are unknown. Two isoforms of the
      allergen were expressed in Escherichia coli and subsequently purified. Conversion
      of these preparations to various forms with molecular size between 10 and 20 kD
      in the presence of nasal secretion was observed. Surprisingly, in skin prick test
      assays with allergic patients the mixture of converted peptides caused
      significantly higher allergic response when compared with the parent protein.
      Allergenic activity of the recombinant N-terminal Phl p5a and the C-terminal Phl
      p5b as measured by skin prick test and histamine release assays was significantly
      higher than that of the respective parent molecules. Using pancreatic rather than
      nasal secretion, Phl p5b was completely degraded and its allergenicity was almost
      completely reduced. Proteolytic degradation converts Phl p5 to defined fragments
      with increased allergenicity. Complete degradation of Phl p5 on the mucosa could
      be a preventive strategy to destroy its potency for the induction of an allergic
      response.

PMID- 9563751
TI  - Peritonitis causes diaphragm weakness in rats.
AB  - Respiratory failure is a common and often lethal complication of severe
      peritonitis. Because this inflammatory process develops in the abdomen, adjacent
      to the diaphragm, we hypothesized that peritonitis might directly compromise
      diaphragm function. We tested this hypothesis using male Sprague-Dawley rats. We
      injected oyster glycogen into the rats' peritoneum, and 16 h later the peritoneum
      was lavaged for leukocyte analysis and muscle samples were excised. Contractile
      properties of diaphragm fiber bundles were measured in vitro. We found that
      neutrophils and macrophages were concentrated in peritoneal lavage fluid of
      experimental animals (p < 0.01) and were adherent to the abdominal surface of the
      diaphragm. Immunohistochemistry showed increases in inducible nitric oxide
      synthase in microvessels of the diaphragm and limb skeletal muscles but not in
      heart or spleen. Peritonitis decreased maximal force production by the diaphragm
      (23.6+/-0.6 versus 21.2+/-0.6 N/cm2; p < 0.05) and decreased the absolute forces
      developed at physiologic stimulus frequencies (> 30 Hz; p < 0.01), depressing the
      overall force-frequency relationship (p < 0.001). Peritonitis had little effect
      on acute muscular fatigue. These data demonstrate that peritonitis weakens the
      diaphragm in rats and suggest that humans with peritonitis may be predisposed to
      respiratory muscle dysfunction.

PMID- 9563752
TI  - Low-dose N-acetylcysteine protects rats against endotoxin-mediated oxidative
      stress, but high-dose increases mortality.
AB  - We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on oxidative
      stress, lung damage, and mortality induced by an endotoxin (lipopolysaccharide,
      or LPS) in the rat. Continuous intravenous infusion of 275 mg NAC/kg in 48 h,
      starting 24 h before LPS challenge, decreased hydrogen peroxide (H2O2)
      concentrations in whole blood (p < 0.01). This decrease was accompanied by fewer
      histologic abnormalities of the lung and decreased mortality (p < 0.025),
      compared with rats receiving LPS alone. N-Acetylserine, which has no sulfhydryl
      group, did not protect rats against LPS toxicity. Improved survival was not
      associated with an increase in pulmonary reduced glutathione, nor with inhibition
      of serum tumor necrosis factor (TNF) activity. In vitro, TNF production and DNA
      binding of nuclear factor kappa B (NF-kappaB) in human Mono Mac 6 cells was only
      inhibited at concentrations of NAC above 20 mM. High-dose NAC treatment (550 and
      950 mg/kg in 48 h) decreased lung GSH (p < 0.05) and resulted in a significantly
      smaller number of surviving animals when compared with the low-dose NAC group (p
      < 0.025). In vitro, NAC increased hydroxyl radical generation in a system with
      Fe(III)-citrate and H2O2 by reducing ferric iron to its catalytic, active Fe2+
      form. We conclude that low-dose NAC protects against LPS toxicity by scavenging
      H2O2, while higher doses may have the opposite effect.

PMID- 9563753
TI  - Lung reperfusion injury after chronic or acute unilateral pulmonary artery
      occlusion.
AB  - Because the lungs receive their blood supply from both the pulmonary and
      bronchial systems, chronic pulmonary artery obstruction does not necessarily
      result in severe ischemia. Ischemia-reperfusion (IR) lung injury may therefore be
      attenuated after long-term pulmonary artery obstruction. To test this hypothesis,
      isolated left lungs of pigs were reperfused two days (acute IR group) or 5 wk
      (chronic IR group) after left pulmonary artery ligation and compared to those of
      sham-operated animals. The severity of IR-lung injury after 60 min ex vivo
      reperfusion of the left lung was assessed based on lung histology and
      measurements of filtration coefficient (Kfc), pulmonary arterial resistance
      (Rpa), and lung myeloperoxidase (MPO) activity. Marked bronchial circulation
      hypertrophy was seen in the chronic IR group. Hemorrhagic alveolar edema was
      found in all acute IR lungs but not in sham or chronic IR lungs. Compared with
      the sham-operated controls, Kfc and Rpa increased two-fold and threefold, and MPO
      1.5-fold and twofold in the chronic and acute IR groups, respectively. In
      conclusion, IR-induced lung injury was markedly reduced when it occurred 5 wk
      after pulmonary artery ligation, probably because the systemic blood supply to
      the lung had time to develop, limiting ischemia.

PMID- 9563754
TI  - Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.

PMID- 9563755
TI  - Respiratory failure and hypoventilation secondary to neurosarcoidosis.
AB  - We report a patient manifesting severe hypoventilation resulting from
      diaphragmatic paresis secondary to sarcoid. A 34yr-old female presented with
      chest pain. Chest radiograph revealed hilar adenopathy and left pleural effusion;
      computed tomography scan showed a 2-cm solid lesion in the aorto-pulmonary
      window. Bronchoscopy and thoracentesis failed to further identify the nature of
      the lesion. An episode of aspiration resulted in cardiopulmonary arrest,
      necessitating cardiopulmonary resuscitation. Electrodiagnostic findings were
      consistent with bilateral phrenic neuropathy with axon loss, suggesting a poor
      prognosis. Biopsy via mediastinoscopy revealed noncaseating confluent granulomas
      with many multinucleated epithelioid histiocytes consistent with the diagnosis of
      sarcoidosis. Eight months after initial diagnosis and immunosuppressive
      treatment, the patient was successfully extubated and became ambulatory. Upon
      tapering her prednisone, however, she became dyspneic and manifested
      hypoventilation secondary to muscle weakness. Her corticosteroids were increased,
      but she eventually died of an opportunistic lung infection 2 yr later. This case
      establishes phrenic neuropathy and peripheral polyneuropathy secondary to
      neurosarcoidosis as a cause of respiratory failure. It also illustrates the
      utility of phrenic and diaphragmatic electrodiagnosis in the evaluation as well
      as prognostication of such lesions.

PMID- 9563756
TI  - Reduced E-cadherin expression is associated with increased lymph node metastasis
      and unfavorable prognosis in non-small cell lung cancer.
AB  - E-cadherin is a calcium-dependent, epithelial cell adhesion molecule whose
      reduced expression has been associated with tumor dedifferentiation and increased
      lymph node metastasis in clinical studies involving several carcinomas. In this
      study, 111 patients who had previously undergone complete resection and
      systematic mediastinal lymph node dissection for non-small cell lung cancer
      (NSCLC) were studied retrospectively. In the primary tumor, as well as in the
      lymph node metastases, E-cadherin expression was detected by immunohistochemistry
      using a monoclonal antibody (HECD-1; Takara, Otsu, Japan). There was a
      significant inverse correlation between E-cadherin expression and lymph node
      stage (Pearson correlation coefficient -0.52, p = 0.0001) as well as tumor
      differentiation (Pearson correlation coefficient -0.27, p = 0.005). Moreover,
      Kaplan and Meier survival estimates showed a significant correlation between E
      cadherin expression and patient survival in log rank testing (p = 0.006). In the
      patient group with the highest proportion of E-cadherin positive tumor cells, 60%
      of the patients were still estimated to be alive at 36 mo, versus 32% of the
      patients in the group classified as showing negative E-cadherin expression. Our
      findings provide clinical evidence that reduced E-cadherin expression is
      associated with tumor dedifferentiation, increased lymphogenous metastasis and
      poor survival. It seems therefore that E-cadherin expression might be an
      important prognostic factor in NSCLC.

PMID- 9563757
TI  - Bacillus Calmette-Guerin revaccination questionable with low tuberculosis
      incidence.
AB  - Bacillus Calmette-Guerin (BCG) revaccination was discontinued in Finland in 1990.
      The objective of this study was to assess the impact of BCG revaccination of
      tuberculin-negative school-children in prevention of tuberculosis. The
      tuberculosis cases in 1990-1995 were calculated among age cohorts born 1979-1984
      and no longer covered by the BCG revaccination program. Corresponding data were
      collected for comparison from the period of revaccination in 1980-1985 among age
      cohorts born in 1969-1974. The National Tuberculosis Register was reviewed in
      order to observe the tuberculosis trend since 1980 in the age groups of 10-14 and
      15-19 yr. Three cases of tuberculosis have been registered among non-BCG
      revaccinated children during 6 yr after discontinuation of the program, i.e.,
      2.23 cases (95% CI 0.72 to 6.90) per million person yr. The control group
      revealed five cases, 3.78 (95% CI 1.57 to 9.07) per million person yr. The
      relative risk of tuberculosis in non-BCG-revaccinated children is 0.59 (95% CI
      0.14 to 2.47) compared with the control group. The incidence of tuberculosis has
      continued to decline among adolescents since 1980. The follow-up data confirm
      that the cessation of BCG revaccination program had no effect on the continuing
      overall decline of tuberculosis in Finland. The efficacy of BCG revaccination
      seems to be low or nonexistent in countries with low tuberculosis incidence.

PMID- 9563758
TI  - Tumor necrosis factor and interleukin-1 inhibitors as markers of disease activity
      of tuberculosis.
AB  - Serum concentrations of tumor necrosis factor-alpha (TNF), interleukin (IL)
      1beta, and their circulating inhibitors soluble TNF receptor type I (sTNFRI),
      type II (sTNFRII), IL-1 receptor antagonist (IL-1ra), and soluble IL-1 receptor
      type II (sIL-1RII) were measured for 123 patients with tuberculosis (TB) in
      various stages of disease, in persons who had been in close contact with patients
      with contagious pulmonary TB, and in healthy controls. Levels of sTNFRI, sTNFRII,
      and IL-1ra, but not of sIL-1RII, were elevated in patients with active TB
      compared with contacts and controls and declined during treatment. The
      concentrations of these mediators did not differ between patients with pulmonary
      and extrapulmonary TB. The levels of sTNFRI and IL-1ra were higher in patients
      with fever and anorexia. Neither TNF nor IL-beta was detectable. We conclude that
      serum concentrations of sTNFRs I and II and IL-1ra may serve as markers of
      disease activity of TB. Sequential measurements of these cytokine inhibitors may
      be useful in the monitoring of antituberculous therapy.

PMID- 9563759
TI  - The American-European Consensus Conference on ARDS, part 2: Ventilatory,
      pharmacologic, supportive therapy, study design strategies, and issues related to
      recovery and remodeling. Acute respiratory distress syndrome.
AB  - The acute respiratory distress syndrome (ARDS) continues as a contributor to the
      morbidity and mortality of patients in intensive care units throughout the world,
      imparting tremendous human and financial costs. During the last 10 years there
      has been a decline in ARDS mortality without a clear explanation. The American
      European Consensus Committee on ARDS was formed to re-evaluate the standards for
      the ICU care of patients with acute lung injury (ALI), with regard to ventilatory
      strategies, the more promising pharmacologic agents, and the definition and
      quantification of pathologic features of ALI that require resolution. It was felt
      that the definition of strategies for the clinical design and coordination of
      studies between centers and continents was becoming increasingly important to
      facilitate the study of various new therapies for ARDS.

PMID- 9563760
TI  - Chest radiographic findings in patients with tuberculosis with recent or remote
      infection.

PMID- 9563761
TI  - Recurrence of desquamative interstitial pneumonia after lung transplantation.

PMID- 9563762
TI  - Lung surfactant and neonatal respiratory distress syndrome.

PMID- 9563763
TI  - Impact of advances in physiology, biochemistry, and molecular biology on
      pulmonary disease in neonates.

PMID- 9563764
TI  - Pulmonary cell biology.

PMID- 9563766
TI  - The mechanics of breathing.

PMID- 9563765
TI  - Pulmonary gas exchange.

PMID- 9563767
TI  - Regulating the ventilatory pump: a splendid control system prone to fail during
      sleep.

PMID- 9563768
TI  - The pulmonary circulation: snapshots of progress.

PMID- 9563769
TI  - Pulmonary edema and acute lung injury research.

PMID- 9563770
TI  - Blood gas analysis and critical care medicine.

PMID- 9563771
TI  - Lung inflammation and fibrosis.

PMID- 9563772
TI  - Asthma.

PMID- 9563774
TI  - Research on cystic fibrosis: a journey from the Heart House.

PMID- 9563773
TI  - Chronic obstructive pulmonary disease (COPD).

PMID- 9563775
TI  - Advances in prevention and education in lung disease.

PMID- 9563776
TI  - NHLBI: fifty years of achievement in pulmonary biology and medicine.

PMID- 9563777
TI  - Human papillomavirus--passenger, driver, or both?

PMID- 9563778
TI  - Downregulation of the beta4 integrin subunit in prostatic carcinoma and prostatic
      intraepithelial neoplasia.
AB  - Integrins are adhesion receptors thought to be important in the process of cancer
      cell invasion and metastasis. Unlike other integrins, which attach a cell to
      extracellular matrix molecules, the alpha6beta4 integrin participates in the
      formation of hemidesmosomes, attaching epithelial cells to the basement membrane.
      Investigations of the alpha6beta4 integrin in human prostatic carcinoma have
      yielded conflicting results and have been primarily qualitative rather than
      quantitative. Expression of the beta4 integrin subunit was determined using rat
      monoclonal antibody 439-9B and image analysis in regions of benign prostatic
      epithelium (BPE), high-grade prostatic intraepithelial neoplasia (PIN), and
      prostatic carcinoma (CaP) in 38 patients treated by radical prostatectomy for
      clinically localized CaP. The beta4 integrin subunit was significantly
      downregulated in CaP compared with BPE; PIN stained intermediate in intensity
      between BPE and CaP. Thirty-four of 35 patients showed downregulation of the
      beta4 integrin subunit, and all 15 patients with PIN had downregulation of beta4
      in PIN as compared with BPE. Degree of downregulation of the beta4 integrin
      subunit did not add prognostic significance to the information present at initial
      biopsy (age, clinical stage, clinical grade, and serum prostate-specific antigen
      level). There was no correlation between intensity of staining of CaP, absolute
      change in staining, or percent loss of beta4 integrin subunit staining with age,
      pathological stage, or Gleason's score. Downregulation of the beta4 integrin in
      CaP and PIN compared with BPE may be correlated with neoplastic transformation of
      the prostate and loss of hemidesmosomes or basal epithelial cells.

PMID- 9563779
TI  - Development of endometriosis from embryonic duct remnants.
AB  - Among 18 cases of endometriosis involving ovaries and fallopian tubes, we
      identified three cases with foci of endometriosis adjacent to the embryonic duct
      remnants in the fallopian tube. The serial sections of the blocks of tissue
      containing areas of interest showed segments of embryonic duct remnants with
      changes suggestive of gradual transformation to endometrial glands. The early
      changes consisted of replacement of the muscular coat surrounding the epithelium
      of embryonic duct remnants by the endometrial stroma with positive
      immunoreactivities for estrogen receptor. Subsequently there were changes of the
      embryonic duct remnant epithelium into endometrial epithelium with diffuse
      immunoreactivities for estrogen receptor. The significance of this transformation
      as a mechanism of development of endometriosis is discussed.

PMID- 9563780
TI  - C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women:
      immunohistochemical analysis and clinicopathologic correlation.
AB  - We studied c-erbB-2, p53, and nm23 gene products in 112 primary breast
      carcinomas. Fifty patients were aged 35 years or younger, and 62 were aged 36 to
      50. Clinicopathological criteria including clinical stage, hormone receptor
      status, histological types, histological grades, and lymph node status, were
      reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed.
      Immunohistochemical findings were assessed semiquantitatively. Correlation
      between clinicopathological criteria, survival data, and immunohistochemical
      findings have been made. Patients aged younger than 35 years with stage I to II
      disease had a shorter DFS (P = .03) than older patients. However, no other
      clinicopathological finding was associated with age. Neither was there
      association between age and c-erbB-2, p53, or nm23 patterns of expression. p53
      positivity was associated with high histological grade (P = .003) and with
      progesterone receptor negativity (P = .045). Nm23 nuclear positivity was
      associated with early clinical stages (P = .011) and with absence of axillary
      lymph node metastasis (P = .007). p53 and c-erbB-2 overexpression were associated
      with shorter OS while nm23 nuclear positivity was associated with longer OS in
      univariate and multivariate analyses. Univariate analyses showed that c-erbB-2 or
      nm23 were potentially important prognostic factors in women aged 35 years or
      younger while p53 was associated with prognosis in women aged 36 to 50. Cox model
      analysis indicated that c-erbB-2 alone was associated with prognosis in women 35
      years and younger, whereas p53 alone was associated with prognosis in 36- to 50
      year-old women. These results suggest that breast cancer in the youngest women
      has some biological specificity.

PMID- 9563781
TI  - Neuroendocrine differentiation in thymic epithelial tumors with special reference
      to thymic carcinoma and atypical thymoma.
AB  - To determine the neuroendocrine (NE) features of thymic epithelial tumor,
      immunohistochemistry and electron microscopy studies were performed on eight NE
      tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five
      atypical thymomas, and 12 thymomas other than lymphocytic thymoma).
      Immunohistochemical studies were performed with antibodies against general
      markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide
      binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a
      broad panel of antibodies for hormonal substances. Thymic carcinoid showed
      synchronous diffuse immunoreactivity for the three NE markers and contained cells
      that were positive for a variety of hormonal products: human chorionic
      gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of
      eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of
      eight), calcitonin gene-related peptide (two of eight), and serotonin (one of
      eight). Conversely, although positivity for NE markers was neither synchronous
      nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five
      atypical thymomas (focal or dispersed distribution), and none of the five
      thymomas were positive for at least two of these NE markers. A small number of
      neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic
      carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG)
      were much more frequent in thymic carcinoid, but several DCG-like granules were
      identified in 12 of 13 non-NE tumors with or without immunoexpression of NE
      markers. The presence of focal or dispersed NE cells in thymic carcinoma and
      atypical thymoma may reflect multidirectional differentiation within the tumor,
      which, like cytological atypia, epithelial CD5 expression, and lack of immature T
      cell infiltration, may be another feature of this group at thymic tumors.

PMID- 9563782
TI  - Hyperplastic mesothelial cells in lymph nodes: report of six cases of a benign
      process that can stimulate metastatic involvement by mesothelioma or carcinoma.
AB  - We report six cases of hyperplastic mesothelial cells located in the sinuses of
      lymph nodes. All patients but one had a concurrent serosal fluid collection (two
      pericardial, two pleural, one abdominal) at the time of the lymph node biopsy.
      All effusions cleared with treatment of the underlying disorder, which included
      lymphoproliferative processes, congestive heart failure, and inflammatory
      diseases (Dressler syndrome, vasculitis, and glomerulonephritis). Four cases were
      associated with vascular prominence of the involved nodal sinuses, a feature that
      may reflect the cause of the underlying effusion or support the transient
      persistence of benign mesothelial cells in lymph nodes. Two cases were
      characterized by distention of the nodal sinuses by sheets of mitotically active
      mesothelial cells. The differential diagnosis includes metastatic carcinoma,
      keratin-positive dendritic cells native to lymph nodes, and metastatic malignant
      mesothelioma. Because the latter shares both clinical and morphological features
      with cases of benign mesothelial cells in lymph nodes, we believe that this
      distinction may not always be possible in a given biopsy specimen and therefore
      that careful clinical follow-up is required in such cases.

PMID- 9563783
TI  - Myofibroblastoma of the breast revisited: an etiologic association with
      androgens?
AB  - Myofibroblastoma of the breast is an uncommon benign stromal tumor encountered
      predominantly among elderly men. Histologically, myofibroblastoma is a well
      circumscribed tumor comprised of bipolar spindle cells arranged in short
      fascicles traversed by collagen bundles. Based on previous histological,
      immunohistochemical, and ultrastructural observations, this tumor is thought to
      be derived from myofibroblasts. The pathogenesis of myofibroblastoma is unknown.
      Given the demographics of this lesion, the established trophic effect of steroid
      hormones, and the potential diagnostic utility of hormone receptor analysis in
      differentiating spindle cell tumors, we immunohistochemically tested for estrogen
      and androgen receptors in a host of spindle cell lesions including
      myofibroblastoma of the breast. Five cases reported herein of histological
      confirmed myofibroblastoma obtained from male and female breasts each showed
      strong nuclear antibody staining for the androgen receptor, not seen in four
      cases of leiomyosarcoma, three cases of fibromatosis, three cases of
      dermatofibrosarcoma protuberans, and two cases of monophasic synovial sarcoma. We
      postulate that the androgen receptor or its ligands may be pathologically related
      to the development of myofibroblastoma of the breast and diagnostically useful in
      differentiating it from other spindle cell lesions.

PMID- 9563784
TI  - Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms
      with increasing grade of malignancy.
AB  - Because glioblastoma multiforme (GBM) frequently shows striking, glomeruloid
      microvascular proliferation (MVP), this tumor has become a strong candidate for
      anti-angiogenic therapy. However, the efficacy of anti-angiogenic treatment may
      rather be determined by the extent of classic angiogenesis with the formation of
      delicate microvascular sprouts. Therefore, this study differentially quantifies
      the microvascular changes in supratentorial diffuse astrocytic neoplasms by
      computerized image analysis of histological sections in which the microvessels
      were highlighted by a combined anti-collagen IV/MIB-1 staining. Four
      microvascular parameters (number, area, perimeter, diameter), the cellularity of
      the glial tissue, and the MIB-1 labeling index were assessed in biopsies of
      astrocytoma (A, n = 13), anaplastic astrocytoma (AA, n = 14), and GBM (n = 20),
      and in normal cerebral cortex (n = 7) and white matter (n = 7). In As and AAs,
      the microvascular parameters were not significantly different from each other,
      and the microvascular changes were generally limited compared with WM and CX. In
      contrast, in GBMs the microvascular parameters were highly variable, and their
      overall mean value was significantly increased compared with As and AAs (ranging
      from 1.3x for vessel diameter to 3.3x for vessel area). Our study indicates that
      not only glomeruloid MVP, but also classic angiogenesis, occurs mainly and only
      locally in GBMs. Thus, this study provides evidence that As and AAs are not good
      candidates for anti-angiogenic therapy. The efficacy of such therapy for GBMs
      awaits further evaluation.

PMID- 9563785
TI  - Cellular proliferation, estrogen receptor, progesterone receptor, and bcl-2
      expression in GnRH agonist-treated uterine leiomyomas.
AB  - Gonadotropin-releasing hormone (GnRH) agonists are commonly used in the treatment
      of uterine leiomyomas, but little is known about their histological and cellular
      effects on these neoplasms. We examined a cellular proliferation index as
      determined by the nuclear antigen Ki-67 and proliferating cell nuclear antigen
      (PCNA) expression, estrogen receptor (ER), and progesterone receptor (PR)
      expression in 27 leiomyomas from patients treated with the GnRH agonist
      leuprolide acetate (LA) and compared them with 33 untreated controls. All
      leiomyomas were removed by myomectomies from premenopausal woman after 2 to 6
      months of LA treatment or in the follicular phase of the menstrual cycle in the
      untreated controls. Histological features examined included cellularity, nuclear
      atypia, vascular changes (dilated, thickened, or thrombosed vessels), edema,
      calcification, hemorrhage, necrosis, hyalinization, and mitotic activity.
      Although no difference was found between GnRH-treated and nontreated groups with
      respect to most histological features examined, immunohistochemical studies
      showed a significant decrease in the cellular proliferation index, ER, and PR
      expression in the LA-treated cases compared with nontreated controls. The
      cellular proliferation index, ER, and PR expression decreased by 85%, 49%, and
      36%, respectively, in the LA-treated group as compared with controls (P < .001).
      A subset of cases from the LA-treated and nontreated groups were also analyzed
      with respect to bcl-2 (an inhibitor of apoptosis) expression, and no significant
      difference between the LA-treated and nontreated groups was observed with both
      groups showing a strong (> 75% of cells) cytoplasmic staining pattern. Results of
      this study show that LA treatment of leiomyomas results in a decrease in number
      of cycling cells.

PMID- 9563786
TI  - Loss of heterozygosity in clinical stage IB cervical carcinoma: relationship with
      clinical and histopathologic features.
AB  - Loss of heterozygosity (LOH) has been shown to be an important prognostic factor
      in a variety of malignant neoplasms. The relationship between LOH and established
      histopathological prognostic factors in cervical carcinoma has not been examined.
      We studied LOH in 58 FIGO stage IB cervical cancers treated by radical
      hysterectomy. In a randomly selected subset of 37 of these cases, LOH was
      examined using markers for all 41 chromosomal arms. Seventy-six percent of the 58
      cases and 95% of the extensively studied cases showed LOH at one or more loci.
      The three most common sites of LOH were 3p21, 6p24-p23, and 11q23.3. In the
      extensively studied group, LOH on 11q was associated with extensive lymphvascular
      space invasion (P = .009) and less deeply invasive tumor (P = .042). There was a
      trend for tumors with LOH on 11q to recur, but this was not statistically
      significant. No correlation between the presence of LOH on 3p or 6p and
      lymphvascular space invasion or tumor depth was present. There was no correlation
      between the number of sites of LOH or between the presence of LOH on 3p, 6p, and
      11q and the presence of metastatic tumor in regional lymph nodes, histologic type
      (squamous v nonsquamous), tumor differentiation, maximum tumor size, degree of
      inflammation, pattern of invasion, mitotic rate, or clinical recurrence. In
      summary, tumors with 11q LOH may behave in a more aggressive fashion. Future
      studies of LOH in cervical carcinoma should include histopathological prognostic
      information so that the relationship between LOH and these factors can be
      determined on larger numbers of patients.

PMID- 9563787
TI  - Splenic para-amyloid material: a possible vasculopathy of the acquired
      immunodeficiency syndrome.
AB  - We have observed perivascular para-amyloid in the spleens of acquired immune
      deficiency syndrome (AIDS) patients at autopsy. Whether this phenomenon is unique
      to AIDS patients or is a common degenerative phenomenon in the spleen has not
      been determined. Autopsy spleens from 355 patients (171 AIDS, 184 non-AIDS) were
      graded for presence of splenic para-amyloid material (SPAM) on a scale of 0 to 3.
      The average ages of the AIDS and non-AIDS groups were 38.4 and 60.4 years,
      respectively. All SPAM-positive AIDS cases had age-matched non-AIDS controls.
      Selected positive cases were examined ultrastructurally. Of the 171 AIDS
      patients, 55 had SPAM; in 30 cases, it was considered grade 2 or 3. Although none
      of the non-AIDS cases were graded 2 or 3, eight of them were grade 1. SPAM is
      highly correlated with AIDS (32.1 v 4.3%; P < .0001), with a specificity of 95.6%
      and a positive predictive value of 87.3%. These perivascular deposits correspond
      to areas of periarteriolar lymphoid sheaths and appear to be in continuity with
      arteriolar adventitia. Ultrastructurally, they contain collagen, long-spaced
      collagen, fibrillin, and occasional residual cells. No viral particles were
      noted. SPAM appears to be more prevalent and in greater quantity in AIDS
      patients. It does not correlate with advanced age; it can be mistaken for
      amyloid. Its consistent association with the adventitia of vessels raises the
      possibility of a new vasculopathy of AIDS; it also may be related to follicular
      involution and hyalinization associated with regression of prior follicular
      hyperplasia.

PMID- 9563788
TI  - Production of trophoblastic hormones by transitional cell carcinoma of the
      bladder: association to tumor stage and grade.
AB  - Cancer registration statistics of economically advanced countries indicate that
      bladder carcinoma incidence ranks fourth in men and eighth in women, but a
      reliable tumor marker for predicting the disease course is still lacking. We
      designed an immunohistochemical study to comprehensively assess the trophoblastic
      hormone production profile of transitional cell carcinoma (TCC) of the bladder.
      Moreover, we correlated histological differentiation and tumor stages with marker
      expression and, finally, evaluated a potential tumor origin of hCGbeta core
      fragment (hCGbetacf). To this end, formalin-fixed, paraffin-embedded tumor
      tissues from 104 patients with urothelial neoplasms of various histological
      grades (23 GI, 24 GII, and 38 GIII) and stage (19pTis, 21pTa, 29pT1, and 35pT2
      T4) were analyzed by the immunoperoxidase technique using our own well
      characterized monoclonal antibodies against the glycoprotein hormones human
      chorionic gonadotropin (hCG) and its derivatives hCGalpha, hCGbeta, hCGbetacf,
      luteinizing hormone (LH, LHbeta), follicle-stimulating hormone (FSH, FSHbeta),
      and the protein hormones placental lactogen (hPL) and growth hormone (hGH-V/N).
      Overall, trophoblastic hormone immunoreactivity was found in 36% of TCC. Detailed
      analysis showed 35% hCGbeta, 17% hCGbetacf, 9% hCGalpha, 4% hCG, and 2% hPL
      positive cases. The tumors produced neither GH-N, placental GH-V, nor the
      pituitary gonadotropins FSH/FSHbeta and LH/LHbeta. Marker positivity
      significantly increased with high-grade lesions (26% GI- v 55% GIII-TCC) and
      advanced tumor stages (24% pTa v 63% > or = pT2). Hormone immunoreactivity was
      frequently observed in highly proliferating areas. Our findings, together with
      recent structural and clinical studies, strongly suggest that these hormones, or
      derivates thereof, might act as local tumor growth factors. Normal urothelium,
      urothelial papillomas, and carcinoma in situ showed no positive reactions. All
      tumors producing hCG-derived molecules were negative for the concommitantly
      analyzed neuroendocrine markers chromogranin A, synaptophysin, and neuron
      specific enolase (NSE). In summary, one third of TCC ectopically produce
      trophoblastic hormones, which is specifically correlated with stage and grade.
      Apart from hCGbeta (97% of the marker-positive cases), the intracellular
      occurrence of hCGbetacf, apparently the second most frequently produced marker,
      was surprising, and there was also a lesser degree free hCGalpha and intact holo
      hormone expression. The placental protein hormones PL and GH-V are not
      appropriate tumor marker candidates. Finally, our histogenetic findings support a
      metaplastic origin of the hCG producing choriocarcinomatous phenotype of some
      TCC.

PMID- 9563789
TI  - Human papillomavirus and mixed epithelial tumors of the endometrium.
AB  - Strong epidemiological evidence links human papilloma viruses (HPV) with the
      development of cervical intraepithelial neoplasia (CIN) and invasive cancers of
      the uterine cervix. The localization of HPV DNA sequences high up in the female
      genital tract (in benign and malignant lesions) is not that uncommon, but its
      precise significance is uncertain. In particular, the detection of HPV DNA
      sequences by polymerase chain reaction (PCR) needs careful interpretation,
      because the source of the amplicon may emanate from tumor cells, direct
      contamination from the cervix, or possibly from extratumoral sites in the
      endometrium. We have previously reported the identification of koilocyte-like
      changes in the squamous epithelium of some endometrial adenoacanthomas.
      Adenoacanthomas (adenocarcinoma with squamous metaplasia) are mixed epithelial
      tumors arising in the endometrium composed of malignant glandular areas admixed
      with benign metaplastic squamous epithelium. The rarer adenosquamous carcinoma
      containing both malignant glandular and squamous areas is also described. The
      origin of benign/malignant squamous epithelial islands in endometrial tumors has
      been the subject of speculation, with some investigators considering an origin
      from metaplastic glandular endometrial cells. In this study, we examined 10
      normal endometrial samples, 20 adenocarcinomas, 41 adenocarcinomas with squamous
      metaplasia, and two adenosquamous carcinomas, (including control cervical
      material where possible) for the presence of HPV DNA sequences using nonisotopic
      in situ hybridization (NISH), type-specific HPV PCR, general primer PCR (to
      detect sequenced and unsequenced HPVs), and PCR in situ hybridization (PCR-ISH).
      We did not identify HPV DNA sequences in normal endometrial tissue. In
      adenocarcinomas (endometrioid type), HPV was only identified in 2 of 20 cases by
      PCR, both of which were HPV 11 positive. We were unsuccessful in identifying HPV
      in endometrial carcinomas by NISH or by PCR-ISH, raising the possibility of
      contamination from the cervix in the two positive cases. In adenoacanthomas, a
      low-risk HPV type (HPV 6) was found in 19 of 41 cases. NISH signals were
      intranuclear in location in squamous regions of adenoacanthomas. Additional
      positive nuclei were uncovered using PCR-ISH, which increases the sensitivity of
      standard NISH detection. HPV DNA sequences were located in some malignant
      endometrial glandular epithelial cells, but this accounted for a minority of
      samples. HPV DNA sequences were not detected in extraepithelial sites. Mixed
      infection by two different HPV types was identified in two cases. Most cases
      showed similar HPV types in cervical and endometrial lesions, although discordant
      cases were uncovered. In adenosquamous carcinomas, one case showed mixed
      infection with HPV 6 and 33 by PCR. The apparent segregation of low-risk HPV type
      (HPV 6) with benign squamous metaplastic epithelium in adenocarcinoma with
      squamous metaplasia, and high-risk type (HPV 33) with malignant squamous
      epithelium in adenosquamous carcinoma, raises important questions in relation to
      the role of HPVs in mixed epithelial tumors of the endometrium and their
      interplay in the pathogenesis of squamous metaplasia at extracervical sites.

PMID- 9563790
TI  - Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma
      with ultrastructural evidence of microvilli with rootlets.
AB  - Villin (V) is a glycoprotein of microvilli associated with rootlet formation.
      Most colonic adenocarcinomas have a V positive (+), cytokeratin (CK) 20 (+), CK7
      negative (-) immunophenotype; most lung adenocarcinomas have a CK20(-), CK7(+)
      immunophenotype. The reports of villin immunoreactivity in lung adenocarcinoma
      range from 6% to 68% in studies using various fixations and varied anti-villin
      antibodies. Some lung adenocarcinomas have microvilli with rootlets leading to
      possible diagnostic confusion with metastatic colonic adenocarcinoma to lung.
      Nine primary lung adenocarcinomas with rootlets on ultrastructure (including four
      bronchioloalveolar carcinomas [BAC]), four metastatic lung adenocarcinomas with
      rootlets, nine metastatic colon adenocarcinomas to lung, and 10 randomly selected
      lung adenocarcinomas without rootlets (including five BAC), were immunostained
      with monoclonal antibodies to villin (1D2C3), CK7 (OV-TL12/30), and CK20 (Ks20.8)
      using a streptavidin peroxidase technique with heat-induced epitope retrieval.
      All primary lung adenocarcinomas with rootlets were CK7(+) CK20(-), and six of
      nine (67%) were V(+). Cytoplasmic villin positivity occurred in a diffuse--five
      of nine (56%), focal--two of nine (22%), or brush border pattern--two of nine
      (22%). Two of four metastatic lung adenocarcinomas with rootlets were V(+). One
      metastatic lung adenocarcinoma had a CK7(+), CK20(+), V(-) phenotype. All
      metastatic colonic adenocarcinomas were V(+), CK20(+), CK7(-), and 1 of 10 (10%)
      lung adenocarcinomas without rootlets was V(+), and all 10 were CK20(-), and
      CK7(+). In summary, villin positivity is more common in lung adenocarcinoma with
      rootlets (67%) than those without rootlets (10%). AU primary lung adenocarcinomas
      were CK7(+), CK20(-). The combination of villin, CK 7, and CK 20 is helpful in
      differentiating metastatic colon adenocarcinoma from lung adenocarcinoma with
      rootlets.

PMID- 9563791
TI  - Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes.
AB  - Subcutaneous panniculitic T cell lymphoma (SCPTCL) is characterized by primary
      involvement of the subcutaneous fat in a manner mimicking panniculitis. We
      studied 16 cases of this lymphoma to define its immunophenotypical profile as
      well as cellular origin. Involvement of the subcutaneous fat in a lacelike
      pattern with neoplastic cells rimming individual fat spaces was present in all
      cases. All 16 cases were of T cell phenotype. Thirteen of the 16 cases were CD8+,
      whereas three were negative for both CD4 and CD8. Twelve cases were stained for
      betaF1; of these, eight were betaF1+ and four were betaF1-. Focal staining for
      CD56 and CD30 was seen in 2 of 13 and two of eight cases, respectively. Intense
      diffuse positivity for the cytotoxic granular proteins T cell intracellular
      antigen-1 (TIA-1) and perforin was present in all cases, indicating an origin
      from cytotoxic T lymphocytes. Ten cases studied for Epstein-Barr viral sequences
      were negative. Eight of 9 cases with amplifiable DNA showed a clonal TCR gamma
      gene rearrangement by polymerase chain reaction. Controls included seven cases of
      benign panniculitis and seven other peripheral T cell lymphomas involving the
      skin and subcutaneous tissues: two peripheral T cell lymphomas, not otherwise
      specified (PTL,NOS), four anaplastic large cell lymphomas (ALCL), one T/NK cell
      lymphoma. The seven cases of panniculitis lacked cytological atypia and were
      characterized by an admixture of CD4+ and CD8+ cells with interspersed aggregates
      of L26+ B cells. Only infrequent cells showed staining for TIA-1 and perforin. In
      the control cases of T cell lymphoma, the infiltrate had a tendency for dermal
      and sometimes even epidermal involvement, with sheeting out of malignant cells,
      in contrast to the characteristic subcutaneous localization and rimming of fat
      spaces noted in SCPTCL. The two PTL, NOS were CD4+ and negative for both TIA-1
      and perforin. Although the remaining controls expressed TIA-1 and perforin, in
      keeping with their cytotoxic T or natural killer (NK) cell origin, histological
      and other immunophenotypical features allowed distinction from SCPTCL. Five cases
      of SCPTCL were also stained for apoptosis using a tdt-mediated end labeling kit.
      All cases showed numerous positive apoptotic bodies, suggesting apoptosis as the
      mechanism of cell death in these tumors. Our study indicates that SCPTCL
      constitutes a distinctive clinicopathological entity derived from cytotoxic T
      lymphocytes and should be differentiated from other benign and malignant lymphoid
      infiltrates involving the subcutis. The apoptosis seen in these tumors may be
      mediated by release of cytotoxic granular proteins.

PMID- 9563792
TI  - X-linked Alport syndrome in females.
AB  - Alport syndrome (AS) is in the differential diagnosis of hematuria. Variability
      in clinical presentation and in the ultrastructural changes of the glomerulus can
      make the diagnosis of AS a challenge in female patients. The purpose of this
      report is to present immunostaining for glomerular basement membrane (GBM)
      expression of alpha5(IV) as an adjunctive diagnostic method. Renal biopsy
      specimens from eight female patients with clinical presentation suggestive of AS
      were studied. The patients were between 7 and 36 years of age; six were between
      12 and 15 years. Light microscopy and immunohistochemistry using a monoclonal
      antibody to alpha5(IV) were performed. Controls showed a continuous linear
      pattern along the GBM in normal kidneys and absence in renal biopsy specimens
      from male X-linked AS patients. To express the variability of the ultrastructural
      GBM changes among the patients in the series, we developed a semi-quantitative
      Alport Index, obtained by quantification of severity and extent of
      ultrastructural GBM changes. With immunohistochemistry, we showed an interrupted,
      discontinuous linear pattern for alpha5(IV) in glomeruli from the eight patients
      in the series, confirming the diagnosis of X-linked AS. The ultrastructural
      Alport Index varied between 6 and 47, showing the heterogeneity in the severity
      of the GBM changes, even among the six patients aged between 12 and 15 years. In
      three of the eight biopsy specimens, the predominant change was thin GBM, and the
      Alport Index was below 20. Immunohistochemistry for alpha5(IV) in renal biopsy
      specimens can identify female patients heterozygous for X-linked AS. In this
      series, the method led to the diagnosis of AS in female patients in whom the
      predominant ultrastructural change was thin basement membrane.

PMID- 9563793
TI  - Ectopic thymoma mimicking diffuse pleural mesothelioma: a case report.
AB  - A case of ectopic thymoma of the pleura with a particular growth pattern
      mimicking diffuse pleural mesothelioma is reported. Diagnostic imaging showed
      that the pleural tumor encased the entire left lung. The specimen biopsied from
      the tumor was composed of lymphocytes and epithelial cells, consistent with the
      mixed type of thymoma. The autopsy found no evidence of a mediastinal tumor. An
      involuted thymus was found in the parietal pleural tissue adhered to the apex of
      the left lung. The thymoma was thought to originate from the ectopic thymic
      tissue in the parietal pleura, as a lesion independent from the primary
      mediastinal thymoma, and spread along the pleura like diffuse mesothelioma.

PMID- 9563794
TI  - Oncocytic lipoadenoma of the submandibular gland.
AB  - We report a case of oncocytic lipoadenoma of the submandibular gland, previously
      unrecognized benign tumor of the salivary gland. The patient was a 66-year-old
      Japanese woman with a left submandibular mass, measuring 11 x 7.5 x 5 cm.
      Microscopically, the mass was completely surrounded by a thin fibrous connective
      tissue capsule, and was composed of an intimate admixture of mature fat cells and
      oncocytes. There have been no English reports of such a neoplasm in the salivary
      gland with the exception of one recent case report of lipoadenoma of the parotid
      gland without oncocytic features. We propose the diagnostic term "oncocytic
      lipoadenoma" for this benign tumor.

PMID- 9563795
TI  - Multiple, unique, and common p53 mutations in a thorotrast recipient with four
      primary cancers.
AB  - Four primary cancers found at autopsy of a patient who received the thorium-based
      contrast agent Thorotrast 50 years ago and who was healthy up until a few months
      before his death from liver failure were analyzed for p53 mutations. The data
      suggest that the chronic alpha-irradiation may be a large causative factor.
      Multiple mutations were found in all the cancer tissues: two foci of a
      cholangiocellular carcinoma, a tubular adenocarcinoma of the stomach, a squamous
      cell carcinoma of the lung, and an adenocarcinoma of Vater's ampulla. The total
      number of point mutations detected were 13. Moreover, homozygous aberrations were
      detected in a large area of normal small intestine and noncancer liver tissues
      suggesting that nontumor cells which harbored p53 abnormalities gained a survival
      advantage and clonally expanded.

PMID- 9563796
TI  - Clonal and morphological variation in a posttransplant lymphoproliferative
      disorder: evolution from clonal T-cell to clonal B-cell predominance.
AB  - The majority of posttransplant lymphoproliferative disorders (PTLD) are Epstein
      Barr virus (EBV)-associated and of B-cell origin. A much smaller proportion of
      PTLD are of T-cell origin. We report the clinical, morphological,
      immunophenotypic, and genotypic results of a unique PTLD, initially diagnosed as
      immune mediated thrombocytopenia (ITP), which at presentation was predominantly
      an anaplastic appearing EBV-associated T-cell PTLD and, after reduction in
      immunosuppression and the administration of antiviral agents, predominantly an
      EBV-associated plasma cell rich B-cell PTLD. Subsequent chemotherapy resulted in
      a complete remission. This case has both practical and biological implications.
      It highlights how PTLD may be misdiagnosed as other entities, how biclonal cases
      can have different morphological appearances and include both B- and T-cell
      clones, how PTLD can evolve over time possibly related to immune reconstitution,
      and why PTLD should be rebiopsied when the disease does not respond to decreased
      immunosuppression or recurs.

PMID- 9563798
TI  - Intraprostatic fat.

PMID- 9563797
TI  - Enhanced expression of interleukin-6 in bone and serum of metastatic renal cell
      carcinoma.
AB  - Interleukin-6 (IL-6) is produced by renal cell carcinoma (RCC) cell lines and
      primary tumors. Using immunohistochemical staining in two RCC patients with
      hypercalcemia and high serum levels of free and total IL-6, we showed expression
      of IL-6 in metastatic bone tissue. The role of IL-6 in hypercalcemia and bone
      resorption would suggest that bisphosphonates or dexamethasone could be useful as
      adjuvant therapy for IL-6 dependent bone metastases which fail to respond to
      interferon alpha (IFN) alpha 2a and all trans retinoic acid (ATRA).

PMID- 9563799
TI  - Interferon-gamma-producing cells and inducible nitric oxide synthase-producing
      cells in periapical granulomas.
AB  - Periapical granulomas contain a large number of T lymphocytes and
      monocytes/macrophages and a small number of B lymphocytes and polymorphonuclear
      leukocytes. Sections from eight periapical granulomas were stained by a variety
      of immunohistochemical methods. The vascular endothelial cells stained positively
      for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1.
      Helper T cells were identified by immunostaining for CD4 and stained positively
      for interferon-gamma (IFN-gamma). However, CD4-positive T cells did not stain for
      interleukin-4 (IL-4). Monocytes/macrophages were identified by immunostaining for
      CD68 and stained positively for IL-1alpha or inducible nitric oxide synthase
      (iNOS). IL-1beta could not be detected in the same samples. No cytokine
      expression was observed in B cells identified by immunostaining for CD20. IFN
      gamma- and iNOS-positive cells could not be detected in clinically healthy
      periodontal ligament being used as a negative control. These results suggest that
      the IFN-gamma-producing T cells and iNOS-positive cells may modulate the progress
      of disease in local inflammation sites such as in periapical granulomas.

PMID- 9563800
TI  - Factors for progression of periodontal diseases.
AB  - Progression factors for periodontal diseases have been suggested by in vitro
      study of peripheral blood and gingival cells; however, those factors are not
      established in vivo. This investigation assessed biopsies of three groups of
      gingival tissues: those adjacent to a 1) < or =3 mm (normal), 2) 4-6 mm, and 3)
      >6 mm gingival sulcus, to determine changes in the gingival microenvironment
      coincident to the progression of periodontal disease. Superoxide dismutase (SOD)
      and catalase activity, and IL-12 and bcl-2 levels, were decreased at >6 mm; total
      protein and IL-6 concentrations were increased adjacent to >6 mm, as compared to
      < or =3 and 4-6 mm, sites. Apoptotic cells were evident only within gingiva
      adjacent to >6 mm sites. These data suggest that IL-12 is an important factor in
      the shift from a TH1 to TH2 cell profile and that a favorable gingival
      microenvironment for hyperinflammation may develop coincident to progression of
      periodontal diseases due to decreased bcl-2 and increased IL-6 concentrations
      within gingiva. These changes in the gingival microenvironment could impair
      apoptosis and promote enhanced release of reactive oxygen species (ROS) by
      phagocytes; decreased catalase and SOD activity could promote accumulation of ROS
      and result in additional tissue destruction.

PMID- 9563801
TI  - Decreased expression and release of dipeptidyl peptidase IV (CD26) in cultured
      peripheral blood T lymphocytes of oral cancer patients.
AB  - To investigate the mechanism whereby serum dipeptidyl peptidase (DPP) IV activity
      in oral cancer patients is decreased, we examined the expression of cell surface
      DPP IV, also known as CD26, in cultured peripheral blood T lymphocytes of these
      patients and the amounts of DPP IV released into culture medium; values were
      compared with those found in healthy subjects. When peripheral blood T
      lymphocytes were cultured in the presence of phytohemagglutinin, concanavalin A
      and/or interleukin-2, the proliferative response and expression of CD26 (DPP IV)
      in their plasma membranes were greatly diminished in oral cancer patients as
      compared with those in healthy subjects. In addition, DPP IV activity in
      lymphocyte culture medium was reduced more in oral cancer patients than in
      healthy subjects, indicating decreased shedding of DPP IV from activated T
      lymphocytes in the patients. Based on these findings, it is suggested that
      suppression of DPP IV expression in peripheral blood T lymphocytes is one of the
      important factors involved in the mechanism of decrease of serum DPP IV activity
      in oral cancer patients.

PMID- 9563802
TI  - Detection of telomerase activity in oral lesions.
AB  - Telomerase is a ribonucleoprotein complex intimately associated with cell
      immortalization and neoplastic transformation. In almost all types of cancer this
      enzyme is reactivated and stabilizes telomere length. It may be necessary for
      continuous cell proliferation. In this study we used a non-radioactive polymerase
      chain reaction assay to analyze telomerase activity in various tissue specimens
      taken from the oral cavity. Four of 4 (100%) squamous cell carcinoma cell lines,
      28 of 29 (96%) malignant tumors, 10 of 28 (36%) benign lesions, and none of the
      14 (0%) oral control tissues possessed telomerase activity. Moreover, 4 of 15
      (27%) oral rinses and 3 of 3 (100%) samples of ascites and pleural effusion taken
      from patients with oral malignancy were telomerase positive. These findings
      indicate that the evaluation of telomerase activity in tissue and body fluid
      specimens may provide information useful in the diagnosis of oral malignancy.

PMID- 9563803
TI  - Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral
      lichen planus.
AB  - This study has addressed the question of whether there is selective recruitment
      and distribution of intra-epithelial leucocytes in lesions of oral lichen planus
      (OLP). T-lymphocyte subsets were examined in the epithelium and peripheral blood
      of patients and controls using flow cytometry and double immunofluorescence, and
      the relationship between keratinocyte intercellular adhesion molecule-1 (ICAM-1)
      expression with T-lymphocyte and Langerhans cell (LC) distribution was examined.
      The circulating 'memory' subset (CD45RO+) of T-helper cells (CD4+) was increased
      from 49.1% in controls to 65.7% in patients (P=0.005), while the 'naive' subset
      (CD45RA+), which was absent from control epithelium, comprised 24% of helper
      cells in OLP (P=0.016). Fewer LC expressed CD45RO in OLP than in controls
      (P=0.037) and all T-cell and LC counts were significantly raised in ICAM-1
      expressing areas of epithelium. These data demonstrate changes in intra
      epithelial T-lymphocyte and LC populations compared with normal oral mucosa and
      suggest there is selective recruitment in OLP. In addition, keratinocyte ICAM-1
      expression does appear to be associated with accumulation of infiltrating T
      lymphocytes and LC.

PMID- 9563804
TI  - Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU).
AB  - Previous studies on the frequency of mast cells (MCs) in recurrent aphthous
      ulcers (RAU) have yielded conflicting results. Monoclonal antibodies specific for
      tryptase (AA1) and anti-IgE (polyclonal antibody) were used to identify density
      and distribution of MCs in an immunohistochemical study of RAU (n=15), induced
      oral traumatic ulcers (TUs) (n=9), and control clinically healthy oral mucosa
      (n=15). Results were quantified by means of a VIDAS image analyzer. In all
      sections studied, IgE-positive cells showed similar frequency and distribution to
      tryptase-positive MCs. In RAU lesions, numerous tryptase-positive MCs were found
      in the sub-epithelial lamina propria, but MC numbers in the epithelium were low
      and present only in some RAU biopsies. MCs were also more numerous in RAU
      inflammatory infiltrates (118+/-31 cells/mm2) than those seen in TU-inflammatory
      infiltrates (75+/-18 cells/mm2, P<0.001). MC activation/degranulation, as judged
      by diffuse extracellular tryptase staining, was a common feature within RAU
      inflammatory infiltrates and at RAU-inflammatory infiltrates-connective tissue
      interfaces, which were often associated with connective tissue disruption. MC
      counts in the RAU connective tissue, lateral to the inflammatory infiltrates,
      were significantly greater than in the connective tissue of TUs and of control
      biopsies (124+/-36 vs 73+/-13 vs 69+/-21 cells/mm2, respectively; P<0.001).
      Overall, MCs were significantly increased in aphthae (116+/-26 cells/mm2)
      compared with TU lesions (72+/-11 cells/mm2, P<0.001) and controls (71+/-16
      cells/mm2, P<0.001). In conclusion, MC numbers are increased in a typical
      topographical pattern, and the local MCs show signs of activation/degranulation
      suggesting active involvement of this cell type in RAU pathogenesis.

PMID- 9563805
TI  - Concurrent HPV infection in oral and genital mucosa.
AB  - Screening for human papillomavirus (HPV) types was performed by a PCR-based assay
      on 29 women (mean age 34.0 years, range 21-48 years). HPV-DNA was demonstrated in
      16 women (55.2%), with a detection rate of 37.9% in the oral cavity and 34.5% in
      the genital tract. HPV-16 was the most prevalent genotype (53.8%), followed by
      HPV-6, which was present in 34.6% of the positive samples. Other types were more
      rarely detected. Five subjects showed concurrent genital tract and oral cavity
      infections but HPV type-specific concordance was detected in only 3 patients.
      Multiple HPV infections were found in 9 of the 26 positive samples, where HPV-6
      appeared frequently associated with the other types. These data confirm the
      occurrence of mixed HPV infections and the wide diffusion of different types of
      HPV in the genital mucosa and in the oral cavity; they also stress the need to
      utilize diagnostic methods with a wide typing capacity.

PMID- 9563807
TI  - Obsessive-compulsive disorder in children and adolescents. Clinical guidelines.

PMID- 9563806
TI  - Oral manifestations of HIV infection by gender and transmission category in
      Mexico City.
AB  - A cross-sectional analysis was conducted in Mexico City from September 1989 to
      March 1996, to determine the prevalence of HIV-related oral manifestations by
      gender and route of HIV transmission. The diagnosis of HIV-associated oral
      lesions was based on preestablished criteria. For the statistical analysis chi
      squared and Fisher's exact tests were used where appropriate. Odds ratios were
      calculated as estimates of the relative risks. Control of confounding factors was
      performed by logistic regression models. Oral lesions were present in 75% of 436
      HIV+ patients. Hairy leukoplakia, erythematous and pseudomembranous candidosis,
      angular cheilitis and oral ulcers were frequently found. Patients who contracted
      HIV through blood transfusion were more likely to present erythematous candidosis
      (P=0.005) than subjects who acquired HIV through sexual transmission. Oral ulcers
      were seen only in men (P=0.02) and in individuals who contracted HIV through
      sexual transmission (P=0.02). This study brings valuable data in regard to
      differences in the type and prevalence of HIV-related oral lesions by gender and
      the risk categories analysed, particularly blood transfusion.

PMID- 9563808
TI  - Two-year outcome of children treated for depression.
AB  - Fifty-four children and adolescents (age 8-17) were assessed two years after a
      clinical intervention trial of cognitive-behavioural vs. non-focused treatment
      for depression. Eleven (20.4%) subjects fulfilled criteria for depression, while
      21 (38.9%) reported significant depressive symptoms during the previous year.
      Seventeen young people (31.5%) had a psychiatric disorder (including depression).
      Overall, the sample maintained the improvement since the termination of
      treatment, without detecting specific treatment effects. Presence of depression
      at two-year follow-up was best predicted by self-esteem ratings before and after
      treatment, and co-morbidity at post-treatment. Depression in young life carries a
      high risk of recurrence, despite initial remission. Continuation or preventative
      treatment for young people at risk of relapse needs development and evaluation.

PMID- 9563809
TI  - The Eating Attitudes Test: comparative analysis of female and male students at
      the Public Ballet School of Berlin.
AB  - Differentiated examination of eating attitudes and behaviours of female and male
      German ballet school students with particular reference to their age and analysis
      of common points with and differences from female Anorexia nervosa (A.n.)
      patients. The Eating Attitudes Test (EAT-40) was used. Male and female adolescent
      students of a ballet school and a high school as well as anorectic patients
      participated in this study. EAT totals exhibited by female and male ballet school
      students were higher with significance than those recorded from high school
      students. EAT totals > 30 were reached by 21.6% of female ballet school students
      but by no male ballet school student at all. In the context of certain EAT items,
      a number of differences are described between female ballet school students, on
      the one hand, and female A.n. patients, on the other. No case was identifiable
      which would satisfy ICD-10 criteria for Anorexia nervosa. Attitudes and
      behaviours of adolescent female and male ballet dancers toward eating and their
      own body should be judged with due consideration of their specific living
      conditions.

PMID- 9563810
TI  - Selective mutism among second-graders in elementary school.
AB  - OBJECTIVE: This study assessed the prevalence of selective mutism among second
      graders in elementary school, and examined related issues such as the situations
      in which the children refuse to speak, their performance level at school, and
      some temperamental/behavioural characteristics of these children. METHOD: A
      definition of selective mutism (according to the DSM-IIIR) was sent to all second
      grade teachers in the study area, asking them if there were any children with
      these symptoms in their class. If a positive answer, the teacher was asked to
      fill in a questionnaire concerning the child. RESULTS: The prevalence rate for
      selective mutism was found to be 2%, with girls outnumbering boys. Selective
      mutism had been in progress more than a year in most cases. Most often, the
      children refused to speak to the teacher (58%), and one-fifth spoke to nobody at
      school. One-third of the mute children were performing at a lower level than
      average. Fewer of these children were reluctant to speak to the teacher than were
      mute children with an average or higher than average performance level. The
      children were characterized as shy, withdrawn and serious, with only some being
      hyperactive or aggressive. About one third of the children had had contact with
      health services.

PMID- 9563811
TI  - Birth order in girls with gender identity disorder.
AB  - This study examined the birth order of girls with gender identity disorder (N =
      22). Each proband was matched to 3-7 clinical control girls for age at assessment
      and number of siblings (the mode number of controls per proband was 7) (total N =
      147). The number of older brothers, older sisters, younger brothers, and younger
      sisters was recorded. Slater's birth order index showed that the probands were
      significantly more likely to be early born than were the controls. A modified
      Slater's index also compared the birth order of the probands and the controls
      only to their brothers (when they had one or more) and only to their sisters
      (when they had one or more). Compared to the controls, the probands were born
      early compared to their sisters, but not to their brothers. These findings are
      the inverse of two previous studies of boys with gender identity disorder, who
      were later born relative to clinical control boys, an effect that appeared to be
      accounted for primarily by being born later relative to older brothers, but not
      to older sisters.

PMID- 9563813
TI  - Three-year outcome of disruptive adolescents treated in a day program.
AB  - Adolescents (N = 38) who attended a multi modal day program were matched with a
      control group (N = 35) for age, gender, year of assessment, and on delinquent and
      aggressive scores. Parent and child were separately interviewed three years after
      initial assessment. Adolescents who attended the program functioned better
      overall and were more satisfied with treatment than controls. Both groups showed
      a poor outcome and a decrease in symptom scores. A diagnosis of conduct disorder,
      high delinquency scores and high total problem scores predicted a poorer outcome.

PMID- 9563812
TI  - Children's perceptions of negative events in Northern Ireland: a ten year study.
AB  - This study examines changes in Northern Irish children's perceptions of negative
      events over ten years. Ten year old children's perceptions of potentially
      distressing situations were obtained from two groups of children in 1983 and 1994
      using a 25 item self-report measure. The children's perceptions of the events are
      contrasted across time and also comparisons between socioeconomic and religious
      groups are made. The comparison shows that the children's perceptions of the
      events remains relatively constant across time, with certain events being
      consistently viewed as the most stressful and least stressful across time and
      between groups. Comparison of religious and socioeconomic groups suggests that
      working class and Roman Catholic children in Northern Ireland frequently rate
      negative events as more stressful than others in their cohort.

PMID- 9563814
TI  - Lamotrigine in Rett syndrome: treatment experience from a pilot study.
AB  - This open pilot study was performed to evaluate the effect of Lamotrigine (LTG)
      in girls with Rett syndrome (RS) regarding seizure frequency, effect on gross
      motor dyspraxia and safety. Twelve girls with either the classical form of RS or
      the milder form fruste variants were included. The effect on epilepsy was
      evaluated as seizure frequency, motor performance (video comparison) and safety
      at clinical check up. The dosage of LTG was individualized and related to
      concomitant anti-epileptic drugs. Two of three girls with epilepsy responded
      relatively well to treatment, and for one of them even bad tantrums disappeared.
      LTG was useful in another four girls who became happier, more alert, more able to
      concentrate, and improved in contacting. Only mild adverse reactions as rash and
      tremor were seen. It is concluded that LTG could be worth trying as an adjunct in
      girls with RS, being aware of possible adverse reactions and no effect at all.

PMID- 9563815
TI  - Developing 'FOCUS': a project to promote effective practice in child and
      adolescent mental health services in the UK.
AB  - UK health policy requires child and adolescent mental health service providers to
      demonstrate that their services are effective. The FOCUS project has been
      developed to improve the availability and accessibility of research evidence and
      innovation, to support purchasers in the effective commissioning of services and
      to help providers base service provision on evidence of effectiveness and develop
      methods of evaluation.

PMID- 9563816
TI  - Some thoughts on the pursuit of success in science.

PMID- 9563817
TI  - Highlight: protein folding in vivo.

PMID- 9563818
TI  - Protein self-organization in vitro and in vivo: partitioning between physical
      biochemistry and cell biology.
AB  - Protein folding is a hierarchical process, driven by the accumulation of
      increments of free energy from local interactions between neighboring residues,
      secondary structural elements, domains and subunits. The latter represent
      independent folding units. Thus, the folding kinetics divide into the collapse of
      sub-domains and domains and their merging to form the compact tertiary fold. In
      proceeding to oligomeric proteins, docking of structured monomers is the final
      step. In agreement with this mechanism, in vitro experiments show that the
      overall mechanism of folding and association obeys uni-bimolecular kinetics with
      aggregation as a competing side reaction. In vivo, accessory proteins serve to
      shift the kinetic partitioning between assembly and misassembly toward the native
      state. So far, co- and post-translational protein folding in the cell has been
      withstanding a detailed kinetic analysis. Despite obvious differences between the
      crowded cytosol and optimized in vitro folding conditions, the general mechanism
      of protein self-organization within and without the cell seems to be similar.
      Effects of solvent parameters on the rate and mode of protein folding are less
      significant than predicted. Addition of small ligands and compatible solutes
      allow nucleation steps and viscosity effects to be analyzed. The absence of
      chimeras after synchronous in vitro reconstitution of oligomeric enzymes proves
      subunit interactions to be highly specific.

PMID- 9563819
TI  - How chaperones fold proteins.
AB  - Chaperones are a functionally related group of proteins assisting protein folding
      in the cell under physiological and stress conditions. They share the ability to
      recognize and bind nonnative proteins thus preventing unspecific aggregation. The
      underlying functional principles of the different chaperone classes are beginning
      to be understood. A landmark feature of molecular chaperones is the involvement
      of energy-dependent reactions in the folding process. Nucleotide binding to ATP
      dependent chaperones (e.g. GroEL, Hsp70, Hsp90) leads to sometimes large
      conformational changes in the chaperone which allow to shift between high- and
      low-affinity states for substrate proteins. Interestingly, the ATPase activity
      which is the key determinant for functional cycles is tightly regulated by a set
      of co-chaperones. While for ATP-dependent chaperones binding sites for nucleotide
      and protein are found in one protein, in the case of ATP-independent chaperones
      (e. g. sHsps, SecB) the energy-dependent step is performed by another chaperone
      (Hsp70, SecA). Therefore, the ATP-independent chaperones can be regarded as
      efficient 'holding' components. Cooperation of different chaperone machineries
      creates a synergistic network of folding helpers in the cell, which allows to
      maintain protein homeostasis under conditions nonpermissive for spontaneous
      folding.

PMID- 9563820
TI  - Hsp70 chaperone systems: diversity of cellular functions and mechanism of action.
AB  - Hsp70 chaperone systems play an essential role in the life cycle of many proteins
      not only in an hostile environment but also under normal growth conditions. In
      the course of evolution the diversification of functions was accompanied by an
      amplification of components of the Hsp70 system. Here strategies are reviewed how
      different Hsp70 systems work independently or cooperate with each other in a
      functional network to perform their housekeeping tasks even under stress
      conditions. We further discuss how co-chaperones which act as targeting factors
      regulate the cycle of substrate binding and release upon which the Hsp70
      chaperone activity depends.

PMID- 9563821
TI  - Regulation of the heat shock conjugate Hsc70 in the mammalian cell: the
      characterization of the anti-apoptotic protein BAG-1 provides novel insights.
AB  - The regulation of the chaperone activity of the heat shock cognate Hsc70 protein
      in the mammalian cell involves a cooperation with chaperone cofactors such as
      Hsp40, the Hsp70-interacting protein Hip, and the Hsc70/Hsp90-organizing protein
      Hop. Recent studies have now added another component to the list of Hsc70
      cofactors, the BAG-1 protein. Initially identified as an anti-apoptotic molecule
      and binding partner of the cell death inhibitor Bcl-2, BAG-1 appears to fulfill
      its cellular function through a modulation of Hsc70's chaperone activity. BAG-1
      acts as a nucleotide exchange factor in the Hsc70 ATPase cycle, thereby competing
      with the cofactor Hip which stabilizes the ADP-bound state of Hsc70. The
      functional characterization of BAG-1 thus reveals an unexpected versatility in
      the regulation of Hsc70 and appears to provide a link between apoptosis and the
      cellular chaperone machinery.

PMID- 9563822
TI  - The role of molecular chaperones in protein transport into the mammalian
      endoplasmic reticulum.
AB  - Molecular chaperones belonging to the Hsp70 protein family play various roles in
      posttranslational protein transport into the yeast endoplasmic reticulum (ER):
      (i) Cytosolic Hsp70 (Hsc70) together with the J-domain containing Hsp40 preserves
      the transport competent state of presecretory proteins; (ii) ER-lumenal Hsp70
      (Kar2p or Lhs1p) triggers the initial insertion of precursor proteins into the
      core of the protein translocase in the ER-membrane and cooperates with a J-domain
      containing membrane protein (Sec63p); (iii) the ER-lumenal Hsp70 and its membrane
      receptor also are involved in completion of translocation. Here a working model
      is presented for the putative roles of molecular chaperones in post- as well as
      cotranslational protein transport into the mammalian ER.

PMID- 9563823
TI  - Sequence motifs shared between chaperone components participating in the assembly
      of progesterone receptor complexes.
AB  - Steroid receptors typically exist in a heteromeric complex with Hsp90 and other
      components of the molecular chaperone machinery. Assembly of functional receptor
      complexes follows an ordered pathway involving at least eight chaperone
      components, some only participating in early assembly stages that are
      prerequisite for formation of mature complexes. The mechanisms directing the
      order of assembly steps and the nature of transitional interactions between
      assembly steps are largely unknown, but likely are encoded in the primary
      sequence and functional domains of the participating chaperones. Several common
      sequence motifs are shared between participants that may be key in ordering the
      steroid receptor assembly pathway.

PMID- 9563824
TI  - The preprotein translocase of the mitochondrial outer membrane.
AB  - The translocase components of the mitochondrial outer membrane (Tom) are
      essential for the transfer of preproteins from the cytosol to the mitochondria.
      At least nine Tom components have now been identified and they fall into two
      categories; receptor components and components of the General Import Pore (GIP).
      The receptor components most likely diffuse laterally in the membrane and deposit
      preproteins atthe GIP where they are then inserted into the mitochondria. This
      review focuses on these components and their known interactions in the process of
      preprotein translocation.

PMID- 9563825
TI  - The role of heat shock proteins in the stimulation of an immune response.
AB  - Heat shock proteins (HSP) have been defined as immunodominant, although most of
      them are highly conserved and ubiquitously distributed. Members of the 60, 70 and
      90 kDa HSP families are involved in important aspects of viral and bacterial
      infections, in autoimmune diseases and in cancer immunity. HSP act as
      immunological target structures either by themselves because of an unusual
      expression pattern, or they are carrier proteins for immunogenic peptides. In
      addition to a classical major histocompatibility complex (MHC) restricted T cell
      response, a major contribution in the recognition of heat shock proteins has been
      shown for non-MHC restricted effector cells including gamma/delta TcR positive T
      lymphocytes and natural killer (NK) cells.

PMID- 9563826
TI  - Directionality of polypeptide transfer in the mitochondrial pathway of chaperone
      mediated protein folding.
AB  - Protein folding in mitochondria depends on the functional cooperation of the
      Hsp70 and Hsp60 chaperone systems, at least for a subset of mitochondrial
      polypeptides. As suggested previously, Hsp70 and Hsp60 act sequentially. However,
      recent proposals that the chaperonin Hsp60 functions by releasing substrate
      protein in an unfolded state would predict a lateral partitioning of folding
      intermediates between chaperone systems. Firefly luciferase, carrying a
      mitochondrial targeting signal, was used as a model protein to analyze the degree
      of coupling and the directionality of substrate transfer between the Hsp70 and
      Hsp60 chaperones. In vitro, Hsp60 binds unfolded luciferase with high affinity
      but is unable to promote its folding, whereas the Hsp70 system assists the
      folding of luciferase efficiently. Upon import into yeast mitochondria,
      luciferase interacted first with Hsp70. Surprisingly, most of the protein
      subsequently accumulated in a complex with Hsp60 and never reached the native
      state. Import into mitochondria that lack a functional Hsp60 did not result in
      increased folding, but in the aggregation of luciferase. Thus, in intact
      organelles the two chaperone systems do not function independently in de novo
      folding of aggregation-sensitive proteins but rather act in an ordered pathway
      with substrate transfer predominantly in the direction from Hsp70 to Hsp60.

PMID- 9563827
TI  - The chaperonin containing TCP-1 (CCT) displays a single-ring mediated disassembly
      and reassembly cycle.
AB  - The chaperonin-containing TCP-1 (CCT) assists in the folding of actins and
      tubulins in eukaryotic cells. CCT is composed of 8 subunit species encoded by
      separate genes. CCT purifies as a single hetero-oligomeric protein complex of 950
      kDa through multiple chromatographic and antibody affinity procedures. The CCT 16
      mer contains 7 polypeptide species in equimolar amounts (CCTalpha, beta, gamma,
      delta, epsilon, zeta, eta), together with another subunit (CCTtheta) which is
      around half-molar. Here we show, by in vitro translation of CCT subunit mRNAs in
      rabbit reticulocyte lysate, that none of the CCT subunit proteins are themselves
      folded by CCT. However, the newly translated CCT subunits can incorporate into
      the endogenous CCT complex present in the lysate via a mechanism involving a
      nucleotide-dependent disassembly reaction to produce single-rings and then a
      reassembly reaction whereby free CCT subunits assemble onto these single-rings.
      This cycling behaviour is an inherent property of the CCT chaperonin complex and
      provides a powerful method for introducing single amino acid residue changes into
      this 8578 residue protein complex.

PMID- 9563828
TI  - Experimental and theoretical analyses of the domain architecture of mammalian
      protein disulphide-isomerase.
AB  - The high resolution structure of full-length protein disulphide-isomerase (PDI)
      has not been determined, but the polypeptide is generally assumed to comprise a
      series of consecutive domains. Models of its domain organisation have been
      proposed on the basis of various sequence-based criteria and, more recently, from
      structural studies on recombinant fragments corresponding to putative domains. We
      here describe direct studies of the domain architecture of full-length mammalian
      PDI based on limited proteolysis of the native enzyme. The results are consistent
      with an emerging model based on the existence of 4 consecutive domains each with
      the thioredoxin fold. The model was further tested by expressing recombinant
      fragments corresponding to alternative domain models and to truncated domains;
      the observed properties of these purified fragments supported the 4-domain model.
      A multiple alignment of many PDI-like sequences was generated to test whether
      domain boundaries could be predicted from any features of the alignment, such as
      sequence variability or hydrophilicity; neither of these parameters reliably
      predicted the domain boundaries determined by experiment.

PMID- 9563829
TI  - Enhanced activity of pyrimidine 5'-nucleotidase in rat red blood cells during
      erythropoiesis.
AB  - A nucleotidase that catalyzed selective hydrolysis of pyrimidine 5'-nucleotides
      was investigated in rat red blood cells (RBCs). The enzyme had similar catalytic
      properties to human pyrimidine 5'-nucleotidase I (P5N-I). The P5N-I deficiency
      was known to be closely correlated with the human inherited disease, non
      spherocytic hemolytic anemia. Similar to the human P5N-I, the rat enzyme
      preferentially hydrolyzed 5'-(d)CMP and 5'-UMP but no reactivity was observed
      with any 3'-nucleotide. Molecular mass of the enzyme was estimated to be
      approximately 38 kDa by gel filtration and SDS-polyacrylamide gel
      electrophoresis. Another subclass of pyrimidine 5'-nucleotidase, P5N-II, was also
      present in rat RBCs. This P5N-II-like enzyme, which resembled a 5'(3')
      nucleotidase, preferentially hydrolyzed both 5'- and 3'- of (d)TMP or (d)UMP, but
      no cytosine nucleotide was hydrolyzed by the enzyme. Results from the reactivity
      with the antibody against rat 5'(3')-nucleotidase and estimated subunit molecular
      mass of the enzymes, about 26 kDa, suggested that the P5N-II-like enzyme had a
      similar structure to the 5'(3')-nucleotidase. The P5N-I-like activity in rat RBCs
      increased 5 to 6-fold at 4 days after phenylhydrazine injection, and reached a
      maximum at 6 to 7 days. No change in the activity of P5N-II-like nucleotidase was
      observed during the experimental period. The increase in rat P5N-I activity
      coincided with maturation of the erythrocytes.

PMID- 9563830
TI  - Extramitochondrial ATP/ADP-ratios regulate cytochrome c oxidase activity via
      binding to the cytosolic domain of subunit IV.
AB  - Cytochrome c oxidase from bovine heart contains seven binding sites for ATP or
      ADP and three additional for ADP only, as concluded from competition equilibrium
      dialysis binding studies. The isolated enzyme contains bound cholate which, in
      contrast to bound ATP, is only slowly exchanged by ADP (or ATP). The kinetics of
      the reconstituted enzyme is influenced by extraliposomal (cytosolic) ATP and ADP.
      The Km for cytochrome c is five times higher in the presence of extraliposomal
      ATP than of ADP. These differences of Km values are lost after preincubation of
      the enzyme with a monoclonal antibody to subunit IV. The data demonstrate
      regulation of cytochrome c oxidase activity by the cytosolic ATP/ADP-ratio, in
      addition to regulation by the matrix ATP/ADP-ratio [Arnold and Kadenbach (1997)
      Eur. J. Biochem. 249, 350- 354], both interacting with subunit IV.

PMID- 9563831
TI  - Microanalysis and distribution of cardiac troponin I phospho species in heart
      areas.
AB  - Sequential phosphorylation and dephosphorylation of cTnI by the cAMP dependent
      protein kinase and by protein phosphatase 2A, respectively, produce the non-,
      mono- and bisphosphorylated species (Jaquet et al., 1995, Eur. J. Biochem. 231,
      486-490). The aim of this study was to determine these forms even in small tissue
      samples, e.g. in biopsy probes of approximately 30 mg which would allow to define
      the phosphorylation state of cTnI in heart areas. In order to do so a micro
      isolation procedure for cTnI had to be established. cTnI is extracted from small
      bovine, rabbit and human heart tissue samples (30-100 mg) under special
      conditions avoiding dephosphorylation and is isolated by affinity chromatography
      on cTnC Sepharose. All three species, the bis-, mono- and dephospho cTnI, are
      precipitated quantitatively by acetone, then they are separated by non
      equilibrium isoelectric focusing and quantified by scanning densitometry. The
      method presented here allows to quantify the three cTnI species reproducibly. No
      other phosphorylated species are detected. Truncated cTnI forms of each phospho
      species are found in human biopsy samples due to removal of a approximately 36
      amino acid peptide from the C-terminus. In bovine, human and rabbit heart the
      pattern of the three cTnI phospho species is characteristic for left and right
      atrium, left and right ventricle and septum.

PMID- 9563832
TI  - Retinoids induce differential expression and DNA binding of the mouse germ cell
      nuclear factor in P19 embryonal carcinoma cells.
AB  - The mouse germ cell nuclear factor (GCNF), a member of the nuclear receptor
      superfamily, is highly expressed during gametogenesis and in the developing
      nervous system. The in vitro translated protein binds as a homodimer to the
      direct repeat (DR) of the sequence -AGGTCA- (DR-0). In this report, we
      characterize a DR-0 binding activity in P19 cell extracts that is induced by
      retinoids. This induction is concentration dependent and specific for embryonal
      carcinoma cells. The cellular protein binds with the same specificity as in vitro
      expressed GCNF, but migrates as a slower complex, indicating interaction with
      partner proteins. Because antisera directed against GCNF recognize this complex,
      we propose that GCNF is part of the binding activity. Combining in vitro
      translated GCNF and extracts of non-expressing cells shows that such interactions
      can be formed posttranslationally. Northern analysis demonstrates a concentration
      dependent induction of GCNF mRNA by retinoic acid. A time course shows that the
      level of GCNF binding is transiently elevated, later downregulated, and not
      detectable in differentiated cells. We propose that GCNF regulation is an
      important step during determination of embryonal carcinoma cells.

PMID- 9563833
TI  - Prolyl isomerases do not catalyze isomerization of non-prolyl peptide bonds.
AB  - Prolyl isomerases accelerate the cis <--> trans isomerization of prolyl peptide
      bonds during protein folding and probably also in folded proteins. We asked
      whether this catalytic function is in fact restricted to prolyl bonds or whether
      the isomerizations of 'normal' non-prolyl peptide bonds are catalyzed as well. By
      using the P39A variant of ribonuclease T1 as a substrate we find that the trans -
      > cis isomerization of the Tyr38-Ala39 bond in the refolding of this protein is
      not catalyzed by prolyl isomerases of the cyclophilin, FKBP and parvulin
      families. These enzymes are neither able to catalyze amide bond isomerizations in
      the proline-free model peptide Ala-Ala-Tyr-Ala-Ala.

PMID- 9563834
TI  - Homo-dimeric recombinant dihydrofolate reductase from Thermotoga maritima shows
      extreme intrinsic stability.
AB  - Dihydrofolate reductase (DHFR) from the hyperthermophilic bacterium Thermotoga
      maritima was cloned and expressed in Escherichia coli. Sequence determination of
      the reported dyrA gene was repeated, and a corrected version deposited in the
      nucleotide sequence databank (accession number Y11021). Ultracentrifugational
      analysis and gel permeation chromatography prove that the enzyme forms a stable
      homodimer. The enzyme exhibits long-term stability at physiological temperature
      (80 degrees C) and in the presence of high denaturant concentrations (half-time
      in 6 M guanidinium chloride: 24h). Alignments of DHFRS from different species, as
      well as comparative modeling based on the homology to the crystal structures of
      the enzyme from prokaryotes and eukaryotes, were used to generate a model of the
      three-dimensional structure. The apoenzyme was crystallized and a data set was
      collected to a resolution of about 2 A.

PMID- 9563835
TI  - The RNA product of the Doc retrotransposon is localized on the Drosophila oocyte
      cytoskeleton.
AB  - The Doc retrotransposon of Drosophila melanogaster encodes an RNA with two open
      reading frames (ORFs). ORF1 encodes an RNA-binding protein and overlaps with
      ORF2, which encodes a reverse transcriptase. Retrotransposons transpose to new
      positions in the genome via a full-length RNA intermediate. Because they do not
      encode a coat protein, transposition is limited to single cell lineages. In this
      paper we present evidence that shows that the highest levels of Doc transcripts
      are found in the adult male and female germ-line. The Doc RNA is localized in the
      region of the cytoskeleton of the Drosophila oocyte. The biological significance
      of this is unknown, but we discuss some of the possibilities.

PMID- 9563836
TI  - Mutant PCNA alleles are associated with cdc phenotypes and sensitivity to DNA
      damage in fission yeast.
AB  - Twenty-eight site-directed mutations were introduced into the fission yeast gene
      (pcn1+) that encodes proliferating cell nuclear antigen (PCNA) and their in vivo
      effects analyzed in a strain with a null pcn1 background. Mutants defective in
      enhancing processivity of DNA polymerase delta have previously been identified.
      In this study, we assessed all of the mutants for their sensitivities to
      temperature, hydroxyurea, UV irradiation and methyl methanesulfonate (MMS), and
      specific mutants were also tested for sensitivity to gamma irradiation. One cold
      sensitive allele, pcn1-3, was characterized in detail. This mutant had a
      recessive cold-sensitive cdc phenotype and showed sensitivity to hydroxyurea, UV,
      and gamma irradiation. At the non-permissive temperature pcn1-3 protein was able
      to form homotrimers in solution and showed increased stimulation of both
      synthetic activity and processivity of DNA polymerase delta relative to the wild
      type Pcn1+ protein. Epistasis analyses indicated that pcn1-3 is defective in the
      repair pathway involving rad2+ but not defective in the classical nucleotide
      excision repair pathway involving rad13+. Furthermore, pcn1-3 is either
      synthetically or conditionally lethal in null checkpoint rad backgrounds and
      displays a mitotic catastrophe phenotype in these backgrounds. A model for how
      pcn1-3 defects may affect DNA repair and replication is presented.

PMID- 9563837
TI  - A stable shuttle vector system for efficient genetic complementation of
      Helicobacter pylori strains by transformation and conjugation.
AB  - A versatile plasmid shuttle vector system was constructed, which is useful for
      genetic complementation of Helicobacter pylori strains or mutants with cloned
      genes of homologous or heterologous origin. The individual plasmid vectors
      consist of the minimal essential genetic elements, including an origin of
      replication for Escherichia coli, a H. pylori-specific replicon originally
      identified on a small cryptic H. pylori plasmid, an oriT sequence and a multiple
      cloning site. Shuttle plasmid pHel2 carries a chloramphenicol resistance cassette
      (catGC) and pHel3 contains a kanamycin resistance gene (aphA-3) as the selectable
      marker; both are functional in E. coli and H. pylori. The shuttle plasmids were
      introduced into the H. pylori strain P1 by natural transformation. A efficiency
      of 7.0 x 10(-7) and 4.7 x 10(-7) transformants per viable recipient was achieved
      with pHel2 and pHel3, respectively, and both vectors showed stable, autonomous
      replication in H. pylori. An approximately 100-fold higher H. pylori
      transformation rate was obtained when the shuttle vectors for transformation were
      isolated from the homologous H. pylori strain, rather than E. coli, indicating
      that DNA restriction and modification mechanisms play a crucial role in plasmid
      transformation. Interestingly, both shuttle vectors could also be mobilized
      efficiently from E. coli into different H. pylori recipients, with pHel2 showing
      an efficiency of 2.0 x 10(-5) transconjugants per viable H. pylori P1 recipient.
      Thus, DNA restriction seems to be strongly reduced or absent during conjugal
      transfer. The functional complementation of a recA-deficient H. pylori mutant by
      the cloned H. pylori recA+ gene, and the expression of the heterologous green
      fluorescent protein (GFP) in H. pylori demonstrate the general usefulness of this
      system, which will significantly facilitate the molecular analysis of H. pylori
      virulence factors in the future.

PMID- 9563838
TI  - Relief of transcriptional polarity by a mutation that creates a promoter in the
      hisG gene of Salmonella typhimurium LT2.
AB  - Six mutant strains were independently isolated in Salmonella typhimurium as non
      polar revertants of a polar Tn10 insertion in hisG. DNA sequence analysis showed
      that all six mutants result from the same nucleotide alteration: a G/C to A/T
      transition 4 bp from the end of the hisG coding sequence. We present data
      suggesting that the mutation (hisG10225) acts by creating a new transcriptional
      initiation signal. Furthermore, the hisG10225 mutation renders the hisG gene
      product cold sensitive.

PMID- 9563839
TI  - Unique organization of the dnaA region from Prochlorococcus marinus CCMP1375, a
      marine cyanobacterium.
AB  - In order to study DNA replication control elements in cyanobacteria we cloned and
      sequenced the dnaA gene from the marine cyanobacterium Prochlorococcus marinus.
      The dnaA gene is ubiquitous among bacteria and encodes the DNA replication
      initiation factor DnaA. The deduced amino acid sequence of the P. marinus DnaA
      protein shows highest similarity to the DnaA protein from the freshwater
      cyanobacterium Synechocystis sp. PCC6803. Using a solid-phase DNA binding assay
      we demonstrated that both cyanobacterial DnaA proteins specifically recognize
      chromosomal origins, oriC, of Escherichia coli and Bacillus subtilis in vitro.
      The genetic environment of dnaA is not conserved between the two cyanobacteria.
      Upstream of the P. marinus dnaA gene we identified a gene encoding a putative ATP
      binding cassette (ABC) transport protein. The gor gene encoding glutathione
      reductase lies downstream of dnaA. Comparison of the genetic structure of dnaA
      regions from 15 representative bacteria shows that the pattern of genes flanking
      dnaA is not universally conserved among them.

PMID- 9563840
TI  - Targeted gene inactivation for the elucidation of deoxysugar biosynthesis in the
      erythromycin producer Saccharopolyspora erythraea.
AB  - The production of erythromycin A by Saccharopolyspora erythraea requires the
      synthesis of dTDP-D-desosamine and dTDP-L-mycarose, which serve as substrates for
      the transfer of the two sugar residues onto the macrolactone ring. The enzymatic
      activities involved in this process are largely encoded within the ery gene
      cluster, by two sets of genes flanking the eryA locus that encodes the polyketide
      synthase. We report here the nucleotide sequence of three such ORFs located
      immediately downstream of eryA, ORFs 7, 8 and 9. Chromosomal mutants carrying a
      deletion either in ORF7 or in one of the previously sequenced ORFs 13 and 14 have
      been constructed and shown to accumulate erythronolide B, as expected for eryB
      mutants. Similarly, chromosomal mutants carrying a deletion in either ORF8, ORF9,
      or one of the previously sequenced ORFs 17 and 18 have been constructed and shown
      to accumulate 3-alpha-mycarosyl erythronolide B, as expected for eryC mutants.
      The ORF13 (eryBIV), ORF17 (eryCIV) and ORF7 (eryBII) mutants also synthesised
      small amounts of macrolide shunt metabolites, as shown by mass spectrometry.
      These results considerably strengthen previous tentative proposals for the
      pathways for the biosynthesis of dTDP-D-desosamine and dTDP-L-mycarose in Sac.
      erythraea and reveal that at least some of these enzymes can accommodate
      alternative substrates.

PMID- 9563841
TI  - Processing of plant mitochondrial tRNAGly and tRNASer(GCU) is independent of RNA
      editing.
AB  - The genes encoding pea and potato mitochondrial tRNAGly and pea mitochondrial
      tRNASer(GCU) were analyzed with particular respect to their expression. Secondary
      structure models deduced from the identical potato and pea tRNAGly gene sequences
      revealed A7:C66 mismatches in the seventh base pair at the base of the acceptor
      stems of both tRNAs. Sequence analyses of tRNAGly cDNA clones showed that these
      mispairings are not corrected by C66 to U66 conversions, as observed in plant
      mitochondrial tRNAPhe. Likewise, a U6:C67 mismatch identified in the acceptor
      stem of the pea tRNASer(GCU) is not altered by RNA editing to a mismatched U:U
      pair, which is created by RNA editing in Oenothera mitochondrial tRNACys. In
      vitro processing reactions with the respective tRNAGly and tRNASer(GCU)
      precursors show that such conversions are not necessary for 5' and 3' end
      maturation of these tRNAs. These results demonstrate that not all C:A (A:C) or
      U:C (C:U) mismatches in double-stranded regions of tRNAs are altered by RNA
      editing. An RNA editing event in plant mitochondrial tRNAs is thus not generally
      indicated by the presence of a mismatch but may depend on additional parameters.

PMID- 9563842
TI  - The use of a thermostable beta-glucanase gene from Clostridium thermocellum as a
      reporter gene in plants.
AB  - In order to take advantage of the high thermostability of its product, beta
      1,3;1,4-glucanase (lichenase), we used a modified version of the licB gene from
      Clostridium thermocellum as a reporter gene for the analysis of gene expression
      in transformed plants. The coding region of the licB gene was truncated at both
      ends. The truncated enzyme retained its activity and thermostability. The
      modified gene (m-licB), with and without a plant leader peptide-encoding
      sequence, was expressed in tobacco plants under control of either the
      Agrobacterium octopine TR-DNA 2' gene promoter or the promoter of the gene for
      the small subunit of ribulose-1,5-bisphosphate carboxylase. Expression of licB
      can be measured quantitatively and accurately, the assay is sensitive and simple
      enough to be used for analysis of various gene fusion systems or for screening of
      transformants. The enzyme is very stable and remains active in tissue extracts
      even after storage for 1 year and survives many thawing-freezing cycles. The
      lichenase-encoding gene was expressed at high levels in transformed tobacco
      plants without any apparent detrimental effects on vegetative growth or
      flowering.

PMID- 9563843
TI  - Isolation of lambda and YAC clones from defined regions of the rye genome.
AB  - A dispersed, rye-specific element has been used to isolate clones of rye origin
      from wheat plants containing only a single rye chromosome arm or segment. In this
      way a set of 23 YAC clones has been isolated from the short arm of rye chromosome
      1 (1RS). This technique was extended to isolate clones from a small region of 1RS
      that contains a large number of agronomically important genes. The targeted
      cloning method allowed the isolation of 26 classes of lambda clones representing
      about 5% of the region. Ten of the lambda clones could be mapped to segments
      within this region. A third example of the application of this technique involved
      the isolation of clones from a very small but fully functional rye chromosome,
      the midget chromosome. These clones have allowed the confirmation of the origin
      of the midget from 1RL, and may provide a tool for the isolation of structural
      elements of cereal chromosomes. This technique allows the identification of clone
      libraries for any rye chromosome or chromosome arm, since substitution, addition
      and translocation lines are available for all rye chromosomes. Furthermore, the
      technique allows isolation of clones derived from segments of the rye genome
      recombined into wheat. The method is technically simple and both lambda and YAC
      libraries can be constructed. Synteny between the genomes of the cereals allows
      region-specific libraries from rye to be used to target regions of the wheat and
      barley genomes.

PMID- 9563844
TI  - The Rhizobium etli FixL protein differs in structure from other known FixL
      proteins.
AB  - The central heme-binding domain in the FixL proteins of Sinorhizobium meliloti,
      Bradyrhizobium japonicum, Rhizobium leguminosarum biovar viciae and Azorhizobium
      caulinodans, is highly conserved. The similarity with the corresponding domain in
      the Rhizobium etli FixL protein is considerably less. This observation prompted
      us to analyze the heme-binding capacities of the R. etli FixL protein. The R.
      etli fixL gene was overexpressed in Escherichia coli. In the presence of S.
      meliloti FixJ, the overexpressed R. etli FixL protein was able to enhance FixJ
      mediated activation of an S. meliloti pnifA-lacZ fusion, indicating that the R.
      etli FixL protein possesses an active conformation in E. coli. Subsequently,
      using a non-denaturing gel assay for heme, we analyzed the heme-binding capacity
      of the R. etli FixL protein expressed in E. coli, taking the S. meliloti FixL
      protein as a positive control. The R. etli FixL protein expressed in E. coli does
      not contain a heme group, in contrast to the S. meliloti FixL protein. Therefore
      we conclude that the R. etli FixL is a non-heme protein in the nif regulatory
      cascade.

PMID- 9563845
TI  - Gene cluster for creatinine degradation in Arthrobacter sp. TE1826.
AB  - The genes encoding creatininase (CrnA; 258 residues) and creatinase (CreA; 411
      residues) from Arthrobacter sp. TE1826 were cloned and sequenced. The genes form
      a cluster with the sarcosine oxidase gene (soxA) and its regulator gene (soxR),
      which were cloned previously. The deduced amino acid sequences of CrnA and CreA
      show 35.9% and 63.1% identity, respectively to the corresponding Pseudomonas
      enzymes. CrnA and CreA were purified from the recombinant strains and
      characterized. Other open reading frames (creB and crnB), encoding proteins
      similar to several transporters, were found downstream of creA and crnA,
      respectively.

PMID- 9563846
TI  - Expression of SRY gene transcripts with a longer 3' untranslated sequence in
      adult human male lymphocytes and tumor cells.
AB  - Using 3' RACE PCR and the repeated nested-PCR method, the expression of
      transcripts of the sex-determining gene SRY was investigated in single
      lymphocytes from a human adult male and in male tumor cell lines. The gene is
      functionally transcribed in the early stages of embryogenesis and mRNA is also
      expressed in adult testes. However, in this study, SRY gene transcripts were also
      detected in somatic cells of adult male and in tumor cells. Moreover, this mRNA
      possessed a longer additional untranslated exon. Although expression of the
      transcripts might not have any functional meaning in these cells, these new
      findings support the hypothesis that any given human cell can contain
      illegitimate mRNAs.

PMID- 9563847
TI  - Recommendations to prevent and control iron deficiency in the United States.
      Centers for Disease Control and Prevention.
AB  - Iron deficiency is the most common known form of nutritional deficiency. Its
      prevalence is highest among young children and women of childbearing age
      (particularly pregnant women). In children, iron deficiency causes developmental
      delays and behavioral disturbances, and in pregnant women, it increases the risk
      for a preterm delivery and delivering a low-birthweight baby. In the past three
      decades, increased iron intake among infants has resulted in a decline in
      childhood iron-deficiency anemia in the United States. As a consequence, the use
      of screening tests for anemia has become a less efficient means of detecting iron
      deficiency in some populations. For women of childbearing age, iron deficiency
      has remained prevalent. To address the changing epidemiology of iron deficiency
      in the United States, CDC staff in consultation with experts developed new
      recommendations for use by primary health-care providers to prevent, detect, and
      treat iron deficiency. These recommendations update the 1989 "CDC Criteria for
      Anemia in Children and Childbearing-Aged Women" (MMWR 1989;38(22):400-4) and are
      the first comprehensive CDC recommendations to prevent and control iron
      deficiency. CDC emphasizes sound iron nutrition for infants and young children,
      screening for anemia among women of childbearing age, and the importance of low
      dose iron supplementation for pregnant women.

PMID- 9563848
TI  - Localization and functional domains of the neurofibromatosis type II tumor
      suppressor, merlin.
AB  - The neurofibromatosis type II (NF2) tumor suppressor gene is inactivated in the
      development of familial and sporadic schwannomas and meningiomas. The encoded
      protein, merlin, is closely related to ezrin, radixin, and moesin, which are
      members of the band 4.1 family of membrane/cytoskeletal linker proteins. We have
      examined the localization and effects of overexpressing epitope-tagged full
      length isoforms of merlin as well as amino- and carboxyl-terminal truncations.
      The full-length and the amino-terminal domain of merlin localize to cortical
      actin, particularly areas of dynamic actin rearrangements such as membrane
      ruffles. Furthermore, overexpression of the carboxyl half of merlin induces cell
      death in NIH3T3 cells. The effect is splice-form specific and is not observed in
      the context of the full-length molecule. Thus, as has been described for the
      erzin, radixin, and moesin proteins, the activities of the carboxyl-terminal
      domain of merlin may be suppressed by the amino-terminal domain.

PMID- 9563849
TI  - Distinct mechanisms control the accumulation of the Rb-related p107 and p130
      proteins during cell growth.
AB  - A variety of studies have demonstrated the critical role of the Rb/E2F pathway in
      the control of cell growth and have highlighted a complexity in the accumulation
      of both the E2F family proteins and the Rb family of proteins. Whereas the Rb
      protein is found in both growing and quiescent cells, the accumulation of p130
      and p107 is tightly regulated with respect to the growth state of the cell. The
      p130 protein is found in quiescent cells but not in growing cells, whereas the
      inverse is true for the p107 protein. Control of p130 accumulation is
      posttranscriptional, because p130 RNA is relatively constant in growing and
      quiescent cells. The disappearance of the p130 protein after stimulation of cell
      growth coincides with cyclin-dependent kinase-mediated phosphorylation and is
      blocked by inhibitors of the 26S proteasome. In contrast, the cell growth
      dependent regulation of p107 expression reflects the transcriptional regulation
      of the p107 gene. Similar to several other growth-regulated genes, the control of
      p107 expression is largely the result of E2F-dependent repression in quiescent
      cells. These experiments thus demonstrate a control of Rb family member
      expression mediated through distinct mechanisms of both transcriptional and
      posttranslational control and also suggest an intimate relationship in which p130
      controls the expression of p107.

PMID- 9563850
TI  - Inhibition of angiogenic differentiation of human umbilical vein endothelial
      cells by curcumin.
AB  - Angiogenesis is a crucial step in the growth and metastasis of cancers. Curcumin
      inhibits tumor initiation and growth. We analyzed the effect of curcumin on
      endothelial cell migration, attachment, and tube formation on Matrigel. Curcumin
      had no effect on endothelial cell migration or attachment to either plastic or
      Matrigel. Curcumin treatment resulted in a dose-dependent inhibition of tube
      formation when the cells were treated before plating or at the time of plating on
      Matrigel. Curcumin treatment also caused the preformed tubes to break down.
      Curcumin inhibited angiogenesis in a s.c. Matrigel plug model in mice. The role
      of metalloproteinases has been shown to be important in angiogenesis; therefore,
      zymography was performed to determine whether curcumin affected protease
      activity. Zymographs of curcumin-treated culture supernatants showed a decrease
      in the gelatinolytic activities of secreted 53- and 72-kDa metalloproteinases.
      Western and Northern analysis showed a dose-dependent decrease in the protein
      expression and transcript of 72 kDa, indicating that curcumin may be exerting its
      inhibitory effect at both the transcriptional and posttranscriptional level.
      These findings suggest that curcumin acts as an angiogenesis inhibitor by
      modulating protease activity during endothelial morphogenesis. Curcumin could be
      developed as an antiangiogenic drug.

PMID- 9563851
TI  - Targeted expression of activated erbB-2 to the epidermis of transgenic mice
      elicits striking developmental abnormalities in the epidermis and hair follicles.
AB  - The erbB-2 proto-oncogene belongs to a receptor tyrosine kinase family that
      includes the epidermal growth factor receptor, erbB-2, erbB-3, and erbB-4. erbB-2
      is expressed in basal cells of the squamous epithelia and the outer root sheath
      of the hair follicles, but its function in epidermal development has not been
      well studied. To investigate its role in the skin, we created transgenic mice
      harboring an activated erbB-2 oncogene under the control of the human keratin 14
      promoter. The keratin 14 promoter directed its expression to cells in which erbB
      2 is normally expressed, whereas the activated receptor gene ensured increased
      signaling. All transgenic founder mice exhibited extensive and striking skin
      phenotype, including epidermal hyperplasia, preneoplasia, papilloma,
      hyperkeratosis, and dyskeratosis. The majority of the hair follicles were
      replaced by bizarre hyperproliferative intradermal squamous invaginations,
      whereas the rest of the follicles exhibited severe hyperplasia and
      disorganization. All but one of the transgenic mice died before or shortly after
      birth, probably as a consequence of defects in the skin and esophagus. These
      observations demonstrate that the skin is sensitive to erbB-2 signaling,
      suggesting an important role for this receptor tyrosine kinase in epidermal
      growth, differentiation, and hair follicle morphogenesis.

PMID- 9563852
TI  - Human annexin 1 is highly expressed during the differentiation of the epithelial
      cell line A 549: involvement of nuclear factor interleukin 6 in phorbol ester
      induction of annexin 1.
AB  - The role of annexin 1 (Ax 1) in cell differentiation was studied in the A 549
      epithelial cell line, a human lung adenocarcinoma line, that responds to phorbol
      esters and glucocorticoids by induction of differentiated properties. Ax 1 has
      also been reported to be involved in the control of cell proliferation. We report
      that Ax 1 synthesis occurs upon phorbol 12-myristate 13-acetate (PMA) treatment
      of A 549 cells and its appearance is correlated with the presence of dipeptidyl
      peptidase IV, or CD26, a marker of epithelial cell differentiation. In addition,
      using transfection experiments and site-directed mutagenesis with the Ax 1
      promoter coupled to a reporter gene, we report that a unique region of the Ax 1
      promoter confers the response of the reporter gene to PMA and dexamethasone. This
      response to PMA and/or dexamethasone involves the induction of the synthesis
      and/or the activity of trans/cis-activating transcriptional factors. Furthermore,
      we have delineated the mechanism of the transcriptional activation of Ax 1 by PMA
      and the involvement of a specific transcription factor, nuclear factor
      interleukin 6 (C/EBP beta).

PMID- 9563853
TI  - Enhanced expression of a new class of liver-enriched b-Zip transcription factors,
      hepatocarcinogenesis-related transcription factor, in hepatocellular carcinomas
      of rats and humans.
AB  - Rat hepatocarcinogenesis-related transcription factor (HTF) was earlier
      identified as a b-Zip transcription factor in chemically induced rat
      hepatocellular carcinoma (HCC) by cDNA subtraction, and its structure was found
      to be different from that of the conventional b-Zip proteins. We investigated htf
      gene expression in rat tissues by Northern analysis and found that HTF expression
      was ubiquitous but was enriched in the liver. HTF expression increased
      concomitantly with HCC development in rat liver, and the HTF-containing DNA
      binding factor also increased. Stimulated HTF gene expression also was observed
      in rat regenerating livers. From the results of various assays, X-box-binding
      protein 1/Tax-response element binding factor 5 was suggested to be a human
      homologue of rat HTF. In humans, HTF gene expression was also abundant in the
      liver and was revealed to be specifically stimulated in HCCs, but not in other
      types of cancers. To our knowledge, HTF is the first example of a liver-enriched
      transcription factor that exhibits HCC-associated gene expression. Injection of
      anti-HTF antibody decreased the growth rate of cultured HCC cells. Consequently,
      HTF is thought to participate in hepatocyte growth as well as in
      hepatocarcinogenesis.

PMID- 9563855
TI  - Lidocaine toxicity: a technical knock-out below the waist?

PMID- 9563854
TI  - Protein kinase C epsilon translocation and phosphorylation by cis
      diamminedichloroplatinum(II) (CDDP): potential role in CDDP-mediated
      cytotoxicity.
AB  - Phorbol ester-like protein kinase C (PKC) activators, such as 12-O
      tetradecanoylphorbol-13-acetate, and perturbation of some growth factor receptors
      have been reported to alter the cytotoxicity of cis-diamminedichloroplatinum(II)
      (CDDP). To study the mechanism of this alteration, we have examined the effect of
      CDDP per se on PKC isozymes. The SKBR-3 human breast carcinoma cell line exhibits
      at least six different PKC isozymes (PKC alpha, betaI, betaII, delta, epsilon,
      and zeta). After exposure to 10-100 microM CDDP for 3 h, only PKC epsilon
      translocated from the plasma membrane to the nuclear membrane and to the
      cytosolic fraction. This translocation was observed in a time- and dose-dependent
      manner by Western blot and confocal microscopy. CDDP also decreased the mobility
      of PKC epsilon in the nuclear membrane fraction, an effect that was blocked by
      protein phosphatase 2A, suggesting drug-mediated isozyme phosphorylation. This
      translocation and phosphorylation were also induced by the cisplatin analogue
      carboplatin but not with the anticancer agents Adriamycin and Taxol. Antisense
      oligodeoxynucleotides against PKC epsilon down-regulated isozyme content, blocked
      drug-induced translocation, and reduced cisplatin-mediated cytotoxicity 3-fold
      compared to that of sense-treated cells. Antisense PKC epsilon also decreased
      SKBR-3 cell sensitivity to carboplatin but not to Adriamycin and Taxol. These
      data support a role for PKC epsilon translocation and phosphorylation on CDDP
      mediated toxicity.

PMID- 9563856
TI  - Pulmonary function in adult survivors of severe acute lung injury treated with
      inhaled nitric oxide.
AB  - BACKGROUND: Following an episode of acute respiratory distress syndrome (ARDS),
      some degree of measurable pulmonary impairment may be anticipated. ARDS is
      thought to be the more severe form of acute lung injury (ALI) and a recently
      proposed addition to conventional therapy in ALI/ARDS is inhaled nitric oxide
      (INO). We carried out a non-randomised follow-up study with pulmonary function
      tests on survivors of severe ALI/ARDS treated with INO. METHODS: Sixteen
      previously healthy pulmonary patients, survivors of severe ALI/ARDS, were
      evaluated with pulmonary function tests >8 months after the acute event. The
      tests included static and dynamic spirometry, diffusion capacity for carbon
      monoxide (DLCO), blood gas analysis and evaluation of a chest radiograph.
      RESULTS: The most common abnormality seen was a low DLCO in 69% of the patients.
      Abnormally low values were seen in forced vital capacity in 31%, in forced
      expiratory volume in 1 s in 13%, and in residual volume and total lung capacity
      in 6%. Blood gas data were within normal limits in 15/16 patients. All chest
      radiographs showed resolution of the interstitial and alveolar changes present
      during the acute event. CONCLUSION: In this non-randomised follow-up study we
      conclude that a degree of measurable pulmonary impairment after INO treatment in
      severe ALI/ARDS was common, but did not differ markedly from other published
      studies on pulmonary function in similar patient material. No late unexpected
      major abnormalities due to the inhaled nitric oxide treatment could be identified
      in these survivors.

PMID- 9563857
TI  - Detrimental effect of a non-selective nitric oxide synthase inhibitor on the
      energy state of the liver following acute endotoxemia in rabbits.
AB  - BACKGROUND: The effect of nitric oxide synthase (NOS) inhibitors in septic shock
      is very controversial. It is known that the administration of NOS inhibitors to
      normal subjects itself increases pulmonary vascular resistance with a concomitant
      decrease of cardiac output. Therefore, the hypothesis was tested that the
      detrimental effects of a non-selective NOS inhibitor on liver energetics in a
      rodent model of endotoxemia are mediated by the adverse pulmonary circulatory
      effect of the drug itself. METHODS: Twenty anesthetized rabbits were instrumented
      and two separate experiments (a magnetic resonance spectroscopic study and a
      hemodynamic study) were performed under similar conditions. Animals were assigned
      randomly to either a control group (group 1; animals received lipopolysaccharide
      (LPS) at a dose of 400 microg/kg alone) or a treatment group (group 2; animals
      received NG-nitro-L-arginine methyl ester (L-NAME) at a dose of 7.5 mg/kg, 75 min
      after administration of LPS). RESULTS: In group 1, slight decreases in hepatic
      adenosine triphosphate (ATP) value were observed. In group 2, the decreases in
      ATP values were more prominent than those observed in group 1. LPS produced an
      acute drop in mean arterial pressure (MAP) with a concomitant increase in
      pulmonary vascular resistance (PVR) and a reduction in the cardiac output (CO) at
      30 min after LPS. The administration of L-NAME caused a transient increase in MAP
      with a concomitant increase in systemic vascular resistance at 2 h after LPS.
      However, these changes in PVR and CO were more prominent than in group 1.
      CONCLUSION: These results suggest that alterations within the pulmonary
      circulation may be a contributing factor which was responsible for the non
      selective NOS inhibitor-induced acute hepatic energy derangement after LPS.

PMID- 9563858
TI  - Retinyl palmitate injections reduce serum levels and effects of endotoxin on
      systemic haemodynamics and oxygen transport in the pig.
AB  - BACKGROUND: Retinyl palmitate [(RP) 230 IU.kg(-1)] modulates the circulatory and
      respiratory responses of a subsequent infusion of endotoxin in the pig. The aims
      of this study were: I. To determine if RP (2300 IU.kg(-1)) affects the serum
      endotoxin levels in this model. II. To evaluate the effect of this dose of RP on
      circulatory and respiratory variables in our porcine model. III. To investigate
      the levels of RP and neutrophil count in porcine endotoxaemia. METHODS: Ten
      anaesthetized pigs were randomly given 2300 IU.kg(-1) of RP or the solvent i.m.
      prior to the continuous i.v. infusion of E. coli endotoxin (10 microg.kg(-1).h(
      1)). Another 4 sham animals were given either i.m. RP (n=2) or i.m. solvent (n=2)
      followed by an infusion of saline. Haemodynamics and oxygen extraction were
      monitored and samples taken for analysis of endotoxin, RP and blood cells.
      RESULTS: I. Endotoxin levels in serum were lower (P<0.001) in the RP-pretreated
      pigs. II. These animals had higher cardiac index (P<0.05), mean arterial pressure
      and left ventricular stroke work index (both P<0.001), and lower oxygen
      extraction (P<0.01). III. RP-Pre=pretreatment caused a paradoxical decrease in
      serum retinyl (P<0.001) and a more rapid restitution of neutrophil count
      (P<0.05). CONCLUSION: Pretreatment with RP (2300 IU.kg(-1)) counteracts the
      progressive increase in serum endotoxin levels in porcine endotoxaemia.

PMID- 9563859
TI  - Bedside troponin T testing is not useful for early out-of-hospital diagnosis of
      myocardial infarction.
AB  - BACKGROUND: A new commercially available rapid qualitative bedside immunoassay
      for cardiac troponin T has been developed. The aim of the study was to
      investigate whether this new rapid bedside cardiac troponin T assay facilitates
      diagnosing myocardial infarction in a pre-hospital setting. METHODS: We evaluated
      the sensitivity and specificity of the new rapid bedside troponin T assay for
      myocardial infarction. In 68 patients with acute, central, crushing chest pain,
      who were strongly suspected of having myocardial infarction, the emergency doctor
      performed preclinically a bedside cardiac troponin T test. The results were
      compared with the diagnosis after admission to hospital, using the criteria of
      the World Health Organization. RESULTS: The diagnosis of myocardial infarction
      was confirmed in 16/68 (24%) patients after admission to hospital, but only in
      4/16 (25%) patients with myocardial infarction was a positive result observed
      preclinically with this test. The result was false positive in 1/5 patients
      (20%). CONCLUSIONS: In contrast to an excellent specificity (0.98), sensitivity
      (0.25) of the rapid troponin T assay was poor. Thus, we conclude that this test
      cannot improve the distinction between myocardial infarction and angina pectoris
      in a pre-hospital setting.

PMID- 9563860
TI  - Metabolic effects of a low-pressure tourniquet system compared with a high
      pressure tourniquet system in arthroscopic anterior crucial ligament
      reconstruction.
AB  - BACKGROUND: Bloodless field is an integral part of orthopedic surgery. Use of
      tourniquet is associated with a risk of skeletal muscle ischemia and reperfusion
      injury. The purpose of this prospective, open-randomized study was to determine
      if the use of a tourniquet system using low pressure, with a wide, curved cuff
      connected to a microprocessor pump is safer than a standard tourniquet system
      with a narrow, straight cuff using higher inflation pressures. METHODS: Test
      parameters used as markers of muscular injury and anaerobic metabolism were
      femoral vein blood lactate, pH, pCO2, pO2, potassium, aspartate aminotransferase
      activity, myoglobin, creatine kinase and creatine kinase-MM activity levels after
      release of tourniquet. Twenty-six ASA I-II patients were studied. RESULTS:
      Tourniquet times varied between 30 and 144 min. Deflation of the tourniquet
      caused a significant release of lactate, myoglobin and potassium detected in the
      femoral vein blood. pCO2 increased, but pH and pO2 decreased after tourniquet
      deflation. There were no differences between the study groups. The tourniquet
      time showed a significant correlation with femoral vein lactate. CONCLUSION: The
      main finding of this study was that the metabolic changes were more pronounced
      with the longer tourniquet time. The results of the study did not show any
      difference on metabolic markers of muscular injury during the first hour after
      release of tourniquet between the two tourniquet systems.

PMID- 9563861
TI  - Transient radicular irritation (TRI) after spinal anaesthesia in day-care
      surgery.
AB  - BACKGROUND: A high incidence of backache with radiating pains to the lower
      extremities, termed transient radicular irritation (TRI), has been reported
      following the use of 5% hyperbaric lidocaine. This has been attributed to a
      neurotoxic reaction. METHODS: A retrospective audit has been carried out in our
      hospital on the postoperative anaesthetic records of all patients from the 1st of
      January 1993 to the 1st of September 1996, who received spinal anaesthesia with
      either hyperbaric lidocaine or hyperbaric bupivacaine for day-care surgery.
      RESULTS: Backache was reported in 1.9% of patients (6/322) receiving hyperbaric
      lidocaine and in 2.4% of patients (1/41) receiving hyperbaric bupivacaine. This
      was not associated with any sensory, motor or sphincter disturbances. One patient
      complained of backache with bilateral pain referred to the gluteal area (TRI),
      which was assessed as acute facet joint syndrome. Unilateral accidental block of
      the femoral nerve was observed in 3 patients, sensory disturbances in the L2/3
      dermatome was reported in a further 3 patients at 24 h, following wound
      infiltration with local anaesthetic during hernia repair. CONCLUSIONS: The low
      incidence of backache at 24 h and the absence of associated symptoms of
      neurogenic pain, sensory and motor disturbances, does not support the hypothesis
      that TRI is a neurotoxic reaction, subsequent to the use of hyperbaric lidocaine.

PMID- 9563863
TI  - Electrophysiological evidence for an antinociceptive effect of ketamine in the
      rat spinal cord.
AB  - BACKGROUND: The dissociative anesthetic ketamine also has antinociceptive
      effects. The mechanism and the site of action of such effect of ketamine have
      been, however, elusive and controversial. The present study was conducted to
      examine the effect of systemically administered ketamine on spinal nociceptive
      transmission. METHODS: We investigated and compared the effects of ketamine (0.25
      8 mg/kg) on the hamstring flexor reflex in intact, lightly anesthetized rats and
      spinally transected rats. The opioid receptor antagonist naloxone was used to
      examine the involvement of opioid receptors in the actions of ketamine. Finally,
      the effects of ketamine on dorsal horn neuronal activity to electrical
      stimulation of peripheral nerves were also studied. RESULTS: Ketamine caused
      similar dose-dependent depression of the hamstring flexor reflex recorded from
      spinally intact rats and from spinalized rats. Even the highest dose of ketamine
      failed to influence the monosynaptic reflex. The depressive effect of ketamine on
      the flexor reflex was not reversed by naloxone. Ketamine i.v. also exerted a
      relatively selective inhibition of the responses of dorsal horn wide-dynamic
      range neurons to C-fiber input of electrical stimulation of the plantar nerve.
      CONCLUSIONS: Our present results support the notion that ketamine can exert a
      direct antinociceptive effect in rat spinal cord. Moreover, the data indicated
      that the spinal antinociceptive effect of ketamine does not involve naloxone
      sensitive opioidergic mechanisms.

PMID- 9563862
TI  - Combined effect of patient variables on sensory level after spinal 0.5% plain
      bupivacaine.
AB  - BACKGROUND: The combined effect of age, weight, height, and vertebral column
      length (VCL) on the distribution of isobaric 0.5% bupivacaine within the
      subarachnoid space is unclear. The aim of the present study was to evaluate the
      combined influence of these patient variables on the upper sensory level and on
      its predictability. METHODS: In 100 patients who were above the age of 49 years,
      the age, weight, height, VCL, body surface (BS), and body mass index (BMI) were
      noted. Spinal puncture and subarachnoid drug administration were standardized.
      Cephalad spread of spinal anaesthesia (SA) was assessed by loss of temperature
      sensation and pinprick discrimination 15, 30, 60, 90, and 120 min following
      subarachnoid injection of 18 mg of plain 0.5% bupivacaine. Linear regression
      analysis was performed for each of the patient variables and the cephalad
      segmental spread of anaesthesia. Multiple regression analysis was used to test
      for combined correlation between patient variables and the sensory level of SA.
      RESULTS: No linear correlation was found between the patient variables and the
      sensory level of anaesthesia. In contrast, multiple regression analysis revealed
      that age (P<0.01), weight (P<0.05), and height (P<0.01) significantly contributed
      to the spread of anaesthesia. A squared multiple comparison coefficient between
      0.10 and 0.21, however, is an indication that the predictive value of the
      combined variables remained rather low. CONCLUSION: Multiple regression analysis
      revealed that age, weight, and height significantly correlated with the sensory
      level after subarachnoid injection of plain bupivacaine. The low predictive value
      suggests that patient factors other than age, weight, or height add to cephalad
      spread of SA.

PMID- 9563864
TI  - Epidural anesthesia and the thermoregulatory responses to hyperthermia-
      preliminary observations in volunteer subjects.
AB  - BACKGROUND: Clinical reports associate the use of epidural anesthesia with an
      increase in core temperature in women in labor. We tested the hypothesis that
      epidural anesthesia alters thermoregulatory responses to hyperthermia in human
      volunteers. METHODS: Each of four volunteers were studied on two days: Control
      and Anesthesia. On the Control day, the subject was warmed via the skin, and the
      core (esophageal) temperature threshold for sweating (detected on the forehead)
      was determined. The subject was then cooled until sweating stopped. The subject
      was warmed again, and a second sweating threshold was determined. The difference
      between the first and second sweating thresholds was noted. On the Anesthesia
      day, two sequential sweating threshold measurements were obtained in a similar
      fashion; however, a mid-thoracic level of epidural anesthesia was established
      before the second sweating threshold measurement. The first and second sweating
      threshold differences were compared between the two study days. The presence or
      absence of sweating on the thigh was noted during all four warming periods.
      RESULTS: Average skin temperatures were similar (about 37 degrees C) during all
      four sweating threshold measurements. On the Control day, the second sweating
      threshold value was always slightly less than the first (average difference
      (mean+/-SD): -0.18+/-0.14 degrees C). In contrast, on the Anesthesia day, the
      second sweating threshold value (determined with an epidural block) was always
      greater than the first (average difference: +0.37+/-0.16 degrees C). Epidural
      anesthesia, therefore, increased the sweating threshold by 0.55+/-0.27 degrees C.
      Epidural anesthesia blocked sweating in the thigh in two of the subjects.
      CONCLUSIONS: An epidural block alters the thermoregulatory responses to warming
      by increasing the threshold for thermoregulatory sweating and, in some cases,
      preventing leg sweating.

PMID- 9563865
TI  - Effects of propofol on ipecacuanha-induced nausea and vomiting.
AB  - BACKGROUND: The purpose of this study was to evaluate if propofol has 5-HT3
      antagonistic effects. Ipecacuanha is known to release serotonin (5-HT) in the
      gastrointestinal tract and therefore ipecacuanha syrup was used to induce nausea
      and vomiting. The 5-HT3 antagonist ondansetron was used as a control substance.
      METHOD: Ten healthy male volunteers (20-37 years) were studied on three occasions
      and were randomly allocated to receive a concomitant infusion of propofol
      (initial bolus 0.1 mg kg(-1) then 1 mg kg(-1)h(-1)), ondansetron (initial bolus
      0.11 mg kg(-1) then 14 microg kg(-1)h(-1)) and placebo on either occasion. The
      infusions started 30 min before oral ingestion of 30 ml of ipecacuanha and
      continued until 150 min after the intake. The number of retchings was recorded
      and the intensity of nausea was estimated by the subjects on a visual analog
      scale. RESULTS: During the first 150 min after ingestion of ipecacuanha there
      were no retchings during the ondansetron infusion (P=0.01 vs placebo, P=0.02 vs
      propofol) and significantly fewer retchings during propofol infusion compared to
      placebo (P<0.02). There was no nausea during the ondansetron infusion (P<0.01 vs
      placebo and propofol) but the volunteers experienced nausea both during the
      placebo and propofol infusion (NS). CONCLUSION: This study in volunteers has
      shown that propofol reduces the intensity of retching after oral intake of
      ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamine, it can be
      concluded that propofol may have a weak 5-HT3 antagonistic effect.

PMID- 9563867
TI  - Effects of four anticholinesterase-anticholinergic combinations and tracheal
      extubation on QTc interval of the ECG, heart rate and arterial pressure.
AB  - BACKGROUND: Imbalance in cardiac sympathetic tone causes prolongation of the QTc
      interval of the ECG. On the other hand, impairment of the parasympathetic control
      of the heart rate caused by anticholinesterase-anticholinergic combinations might
      also affect the cardiac sympathetic tone and hence the QTc interval of the ECG.
      The main purpose of the present study was to compare the effects of four
      anticholinesterase-anticholinergic combinations used for the antagonism of the
      neuromuscular block on the QTc interval of the ECG, heart rate and arterial
      pressure. METHODS: Eighty-four ASA class I-II patients with a mean age of 32 to
      37 yr undergoing otolaryngological surgery were randomly allocated to one of the
      following groups: neostigmine 40 microg/kg+glycopyrronium 8 microg/kg (Ne-Glyc),
      neostigmine 40 microg/kg+atropine 20 microg/kg (Ne-Atr), edrophonium 200
      microg/kg+atropine 300 microg (Edr-Atr (1)), edrophonium 500 microg/kg+atropine 7
      microg/kg (Edr-Atr (2)). QTc interval and heart rate were measured by a signal
      processing method based on an IBM/PC/xT-compatible microcomputer and arterial
      pressure with a sphygmomanometer at 1-min intervals up to 10 min after the
      injection of the drugs and immediately and 2 min after extubation. The ECG, lead
      II, was continuously recorded. Neuromuscular block was measured by a Datex
      relaxograph. RESULTS: In all groups, the most pronounced increase in both QTc
      interval, heart rate and arterial pressure occurred 1 min after the study drugs
      and immediately after extubation. In all groups, the mean QTc intervals at 1 and
      2 min after the study drugs and after extubation were longer than the upper limit
      of the normal range (440 ms). Junctional rhythm occurred in 1 to 3 patients in
      all other groups with the exception of the Edr-Atr(1) group in which no cardiac
      arrhythmias occurred. At 1 min, the heart rate in the Ne-Atr group was at a
      significantly higher level than that in the Ne-Glyc group. From 3 to 6 min, the
      heart rate in the Edr-Atr(2) group and at 3 min in the Edr-Atr(1) group was at a
      lower level than the heart rate in the Ne-Glyc group. CONCLUSIONS: On the basis
      of the present results, anticholinesterase-anticholinergic combinations should be
      avoided in patients having a long QT interval syndrome or a prolonged QT interval
      from other causes. In addition, the cardiovascular stimulation caused by tracheal
      extubation should also be avoided in these patients.

PMID- 9563866
TI  - Propofol and alfentanil total intravenous anaesthesia: a comparison of techniques
      for major thoracic surgery.
AB  - BACKGROUND: Previous work has highlighted the disadvantages of propofol as a sole
      agent for total intravenous anaesthesia (TIVA). This randomised study
      investigated three combinations of propofol and alfentanil as TIVA for major
      thoracic surgery. METHODS: In 73 patients undergoing elective thoracic surgery,
      anaesthesia was conducted either with sodium thiopentone induction and
      inhalational maintenance (incorporating isoflurane) or with TIVA using propofol
      with alfentanil (by infusion at one of two rates or in incremental doses). Vital
      signs and recovery characteristics were recorded. RESULTS: There were no
      significant differences in heart rate or blood pressure between groups during
      either induction or maintenance. Depth of anaesthesia was controlled
      satisfactorily in all groups. Recovery characteristics were similar between
      treatment groups, although there was a trend towards earlier orientation in the
      group which received the highest infusion rate of alfentanil. CONCLUSION:
      Continuous infusions of propofol and alfentanil provide safe and reliable TIVA
      for major thoracic surgery. TIVA was found to be a satisfactory technique in more
      elderly patients than previously described. The higher of the two alfentanil
      infusion rates may result in a better combination of propofol and alfentanil with
      respect to recovery times than the lower.

PMID- 9563868
TI  - Anaesthesia for videoarthroscopy of the knee. A comparison between desflurane and
      sevoflurane.
AB  - BACKGROUND: The newer inhalational agents desflurane and sevoflurane have a low
      blood-gas partition coefficient and are not very fat soluble, and consequently
      recovery is rapid and smooth. Very few studies have been published concerning
      adults where a direct comparison has been made between sevoflurane and desflurane
      in the ambulatory setting. METHODS: This study was done to assess aspects of
      recovery following minor ambulatory videoarthroscopic knee surgery in 50 ASA I-II
      patients. Baseline values were obtained on the following psychomotor tests: digit
      symbol substitution test (DSST), perceptive accuracy test (PAT) and simple
      reaction time (SRT). The patients were then randomly allocated to one of two
      groups according to an open (unblinded) study design: Group D (Desflurane) were
      maintained on desflurane while Group S (Sevoflurane) were maintained on
      sevoflurane. Propofol was used as the induction agent in all patients and the
      larynx mask was used to maintain a free airway. Oxygen and air (FiO2 0.33) were
      used as the carrier gases. The concentration of desflurane or sevoflurane was
      adjusted in order to maintain adequate anaesthesia and stable haemodynamics.
      Alfentanil was given at induction and every 15 min as an analgesic. At the end of
      the operation, the gases were turned off abruptly and 100% oxygen was delivered
      at 6 L/min until eye-opening. Early recovery was measured by the time to eye
      opening, giving name and date of birth. Intermediate recovery was measured by
      psychomotor testing every 30 min, and the time to sitting up in bed, drinking
      fluids and discharge home by a nurse who was blinded to the anaesthetic
      technique. RESULTS: Early recovery was quicker in the desflurane compared to the
      sevoflurane group (P<0.001). Psychomotor recovery as measured by the PAT occurred
      significantly earlier in the desflurane compared to the sevoflurane group at 15
      and 45 min (P<0.001) and as measured by the DSST at 30 min (P<0.05). The number
      of patients who could not perform the SRT test at 15 min was greater in the
      sevoflurane compared to the desflurane group (13 vs 0) (P<0.01). No differences
      were found in other recovery parameters, including home discharge, between the
      groups. The incidence of pain and other minor postoperative complications was
      similar between the groups except for sore throat which was higher in the
      desflurane group. CONCLUSION: Early and intermediate (psychomotor) recovery is
      quicker in the desflurane compared to the sevoflurane group, but there is no
      difference in discharge times between the groups.

PMID- 9563869
TI  - Succinylcholine-induced fasciculations in denervated rat muscles as measured
      using 31P-NMR spectroscopy: the effect of pretreatment with dantrolene or
      vecuronium.
AB  - BACKGROUND: We have previously demonstrated by 31P nuclear magnetic resonance
      (NMR) that succinylcholine (SCh) induces metabolic changes in denervated muscle.
      To specify those changes, we attempted to inhibit them using two different kinds
      of drugs, dantrolene and vecuronium. METHODS: Three weeks after unilateral
      sciatic nerve section, 75 male Wistar rats were randomly assigned to one of the
      following 5 groups: (1) non-pretreated normal muscle group; (2) non-pretreated
      denervated muscle group; (3) denervated muscle group pretreated with a low dose
      of vecuronium (0.02 mg.kg(-1)); (4) denervated muscle group pretreated with a
      high dose of vecuronium (0.2 mg.kg(-1)); (5) denervated muscle group pretreated
      with dantrolene (2 mg.kg(-1)). The change of the inorganic
      phosphate/phosphocreatine (Pi/PCr) ratio of each muscle was measured by 31P-NMR
      before and after SCh (1 mg.kg(-1)) administration and the corresponding peak
      amplitude of the electromyograms (EMG) was determined. RESULTS: The high dose of
      vecuronium totally inhibited SCh-induced fasciculation on EMG (100%-->2%). In
      this group, though the Pi/PCr ratio significantly increased 10 min after SCh, the
      peak after 5 min disappeared. The inhibition with dantrolene was about the same
      order of magnitude as with the low dose of vecuronium (35%:21%). However, the
      increase in the Pi/PCr only lasted about 10 min, in contrast to the other drugs.
      CONCLUSION: Our findings indicate that the Pi/PCr increases 5 and 10 min after
      SCh, respectively, as a result of two different processes. The first peak is
      caused by an excessive energy consumption in response to excessive muscle
      contraction. This in turn triggers the second peak, caused by breakdown of
      glycogen, initiated by an increased Ca2+ concentration.

PMID- 9563870
TI  - Intra- and postoperative myocardial ischemia without significant coronary artery
      stenosis.
AB  - A 73-year-old man without a history of coronary artery disease had two episodes
      of significant ST-segment elevation indicative of inferior myocardial ischemia
      during the resection of an abdominal aortic aneurysm. During the further course,
      sudden ST-segment elevations occurred and resolved spontaneously without
      preceding hemodynamic instability. The patient sustained two episodes of cardiac
      arrest due to ventricular fibrillation and intermittent third-degree
      atrioventricular block with ventricular asystole. On cardiac catheterization,
      coronary arteries had a right dominant pattern. The right coronary artery was
      entirely patent on multiple injections. Thus, right coronary artery spasm is the
      only possible explanation for these observations.

PMID- 9563871
TI  - Myelotoxicity of local anaesthetics.

PMID- 9563872
TI  - What is renal function and how do we assess it?

PMID- 9563873
TI  - About intraoperative perception.

PMID- 9563874
TI  - Interactions between the epidermal growth factor receptor and type I protein
      kinase A: biological significance and therapeutic implications.
AB  - Peptide growth factors regulate normal cellular proliferation and differentiation
      through autocrine and paracrine pathways and are involved in cancer development
      and progression. Among the endogenous growth factors, the epidermal growth factor
      (EGF)-related proteins play an important role in the pathogenesis of human
      cancer. In fact, overexpression of EGF-related growth factors such as
      transforming growth factor alpha and amphiregulin and/or their specific receptor,
      the EGF receptor (EGFR), has been detected in several types of human cancers,
      including breast, lung, and colorectal cancers. Therefore, the blockade of EGFR
      activation by using anti-EGFR monoclonal antibodies (MAbs) has been proposed as a
      potential anticancer therapy. The cAMP-dependent protein kinase (PKA) is an
      intracellular enzyme with serine-threonine kinase activity that plays a key role
      in cell growth and differentiation. Two PKA isoforms with identical catalytic (C)
      subunits but different cAMP-binding regulatory (R) subunits (defined as RI in
      PKAI and RII in PKAII) have been identified. Predominant expression of PKAII is
      found in normal nonproliferating tissues and in growth-arrested cells, whereas
      enhanced levels of PKAI are detected steadily in tumor cells and transiently in
      normal cells exposed to mitogenic stimuli. Overexpression of PKAI has been
      correlated recently with poor prognosis in breast cancer patients. Inhibition of
      PKAI expression and function by specific pharmacological agents such as the
      selective cAMP analogue 8-chloro-cAMP (8-Cl-cAMP) induces growth inhibition in
      various human cancer cell lines in vitro and in vivo. We have provided
      experimental evidence of a functional cross-talk between ligand-induced EGFR
      activation and PKAI expression and function. In fact, PKAI is overexpressed and
      activated following transforming growth factor alpha-induced transformation in
      several rodent and human cell line models. Furthermore, PKAI is involved in the
      intracellular mitogenic signaling following ligand-induced EGFR activation. We
      have shown that an interaction between EGFR and PKAI occurs through direct
      binding of the RI subunit to the Grb2 adaptor protein. In this respect, PKAI
      seems to function downstream of the EGFR, and experimental evidence suggests that
      PKAI is acting upstream of the mitogen-activated protein kinase pathway. We have
      also demonstrated that the functional interaction between the EGFR and the PKAI
      pathways could have potential therapeutic implications. In fact, the combined
      interference with both EGFR and PKAI with specific pharmacological agents, such
      as anti-EGFR blocking MAbs and cAMP analogues, has a cooperative
      antiproliferative effect on human cancer cell lines in vitro and in vivo. The
      antitumor activity of this combination could be explored in a clinical setting
      because both the 8-Cl-cAMP analogue and the anti-EGFR blocking MAb C225 have
      entered human clinical trial evaluation. Finally, both MAb C225 and 8-Cl-cAMP are
      specific inhibitors of intracellular mitogenic signaling that have different
      mechanisms of action compared with conventional cytotoxic drugs. In this respect,
      a cooperative growth-inhibitory effect in combination with several
      chemotherapeutic agents in a large series of human cancer cell lines in vitro and
      in vivo has been demonstrated for anti-EGFR blocking MAbs or for 8-Cl-cAMP.
      Therefore, the combination of MAb C225 and 8-Cl-cAMP following chemotherapy could
      be investigated in cancer patients.

PMID- 9563875
TI  - p53 and RB expression predict progression in T1 bladder cancer.
AB  - The optimal clinical management of minimally invasive (stage T1) bladder cancer
      is controversial. T1 bladder cancers share characteristics of both noninvasive
      (Ta) papillary cancer and high stage, muscle-invasive bladder cancers. Patients
      with T1 bladder cancer have a higher risk of cancer progression and death than do
      patients with Ta bladder cancer. However, this risk is much lower than that of
      patients with high-stage bladder cancers. Methods of identifying T1 bladder
      cancer patients at greatest risk for progression may significantly improve
      clinical management. We retrospectively evaluated two tumor suppressor genes, p53
      and RB, as potential prognostic markers for progression in a cohort of 45
      patients with pT1 bladder cancer. Median follow-up for these individuals was
      greater than 3.5 years. Of this group, 58% had altered p53 expression based on
      positive p53 immunostaining. Three patterns for RB nuclear protein staining were
      observed: absent, heterogeneous (normal), and strongly homogeneous. Progression
      free survival was similar for patients with loss of RB protein expression and
      those with apparent overexpression of RB protein. Therefore, both staining
      patterns were considered abnormal. Patients with normal expression of both
      proteins (i.e., p53 negative and RB heterogeneously positive) had an excellent
      outcome, with no patient showing disease progression, whereas patients with
      abnormal expression of either or both proteins had a significant increase in
      progression (P = 0.04 and P = 0.005, respectively). These data support the
      stratification of T1 bladder cancer patients based on p53 and RB nuclear protein
      status and suggest that patients with normal protein expression for both genes
      can be managed conservatively, whereas patients with alterations in one and
      particularly both genes require more aggressive treatment.

PMID- 9563877
TI  - Cyclin D1 protein is overexpressed in hyperplasia and intraductal carcinoma of
      the breast.
AB  - The cell cycle regulatory gene cyclin D1 is a candidate oncogene in breast
      cancer. It is overexpressed in 30-50% of invasive primary breast cancers and
      plays a key role in mediating mitogenic responses to steroids and growth factors
      in breast cancer cells in vitro. Because the role of cyclin D1 in the
      proliferative and early noninvasive stages of breast cancer is largely unknown,
      we examined normal breast epithelium (NBE), proliferative disease (PD), ductal
      carcinoma in situ (DCIS), and invasive carcinoma (IC) to evaluate the timing and
      possible importance of cyclin D1 expression in the development of breast cancer.
      Using immunohistochemistry, we examined cyclin D1 protein expression in 471
      breast tissue samples. A quantitative scoring system for immunohistochemistry
      based on percentage of positive cells was developed that correlated with Western
      blot analysis of antigen concentration in paired samples (r2 = 0.91, P = 0.003).
      A sample was considered positive if >5% of relevant epithelial cells demonstrated
      nuclear staining. Cyclin D1 positivity was observed in 11.7% (7 of 60) samples of
      NBE, 25% (11 of 44) of PD without atypia, 39.4% (13 of 33) of atypical ductal
      hyperplasia, 43.6% (17 of 39) of low-grade DCIS, 47.9% (23 of 48) of high-grade
      DCIS, and 48.3% (99 of 205) of IC. Cyclin D1 expression was significantly higher
      in PD than NBE (P = 0.006) and in DCIS than PD (P = 0.038). There was no
      significant increase from DCIS to IC (P = 0.52). The increase in cyclin D1
      expression in the overall progression from NBE to IC was also highly significant
      (P = 0.0001). Therefore, cyclin D1 expression was detected at levels
      significantly greater than in NBE in the earliest proliferative epithelial
      lesions of the breast with a further significant increase accompanying the
      progression to any form of cancer. This suggests that overexpression of cyclin D1
      protein is important at the earliest stages of breast oncogenesis and continues
      to have a crucial role throughout the development of malignancy.

PMID- 9563876
TI  - Adenovirus-mediated p53 gene therapy and paclitaxel have synergistic efficacy in
      models of human head and neck, ovarian, prostate, and breast cancer.
AB  - Synergy (or antagonism) between two chemical agents is an in vitro empirical
      phenomenon, in which the observed effect of the combination is more (or less)
      than what would be predicted from the effects of each agent working alone.
      Although mathematical synergy is not directly provable in the clinical setting,
      it does predict a favorable outcome when the two therapeutics are combined in
      vivo and strongly suggests the presence of in vivo synergy. In contrast, overt
      antagonism warns of future problems. Sophisticated three-dimensional statistical
      modeling was used to evaluate the presence of synergistic, additive, or
      antagonistic efficacy between adenovirus (Ad)-mediated p53 gene therapy (p53 Ad)
      and paclitaxel (Taxol) in a panel of human tumor cell lines. Cells were either
      pretreated with paclitaxel 24 h before p53 Ad or treated with both agents
      simultaneously. Cell proliferation was measured 3 days later. Paclitaxel had
      synergistic or additive efficacy with p53 gene therapy. In no case was the
      interaction antagonistic. Cell cycle analysis demonstrated that p53 Ad arrested
      cells in G0/G1 prior to apoptotic cell death, whereas paclitaxel arrested cells
      in G2-M prior to apoptotic cell death. When combined, the relative concentration
      of each agent determined the dominant cellular response. These results are
      consistent with the previously reported cell cycle effects of p53 or paclitaxel,
      respectively; however, these data fail to explain the observed drug synergy. We
      found that low concentrations of paclitaxel (1-14 nM) increased the number of
      cells transduced by recombinant Ad 3-35% in a dose-dependent manner, which is one
      possible mechanism for the observed synergy. Of particular note, the
      concentrations of paclitaxel responsible for increased Ad transduction were lower
      than the concentrations required for microtubule condensation. The efficacy of
      combination therapy was also evaluated in vivo. In the p53null SK-OV-3 xenograft
      model of ovarian cancer, a dosing schedule of p53 Ad that, by itself, had a
      relatively minimal effect on tumor burden (16%) caused a much greater decrease in
      tumor burden (55%) when combined with paclitaxel. Greater combined efficacy was
      also observed in the p53mut DU-145 prostate, p53mut MDA-MB-468 breast, and p53mut
      MDA-MB-231 breast cancer xenograft models in vivo. In summary, p53 Ad for cancer
      shows enhanced efficacy when combined with paclitaxel. This combination is
      recommended for clinical cancer trials.

PMID- 9563878
TI  - Quantitative analysis of carcinoembryonic antigen messenger RNA in peripheral
      venous blood and portal blood of patients with pancreatic ductal adenocarcinoma.
AB  - One major therapeutic failure of pancreatic adenocarcinoma treatment is
      metastasis to the liver. To screen patients with high risk for such hematogenous
      dissemination, we previously developed a very sensitive system to detect
      carcinoembryonic antigen (CEA) in blood. For a more practical application, we
      improved this system by making it quantitative and capable of analyzing both
      preoperative peripheral blood and intraoperative portal blood for the presence of
      CEA mRNA. CEA mRNA was not detected in the peripheral venous blood of any of the
      three patients examined, but it was identified in the portal blood without fail.
      In addition, the quantities of CEA mRNA identified in the portal blood before and
      after pancreatectomy were different. This study suggests that analysis of the
      portal blood seems to be important for the precise evaluation of hematogenous
      dissemination and of the pathophysiology of pancreatic ductal adenocarcinoma.

PMID- 9563879
TI  - Philadelphia chromosome-positive myeloid cells in the peripheral blood of chronic
      myelogenous leukemia patients: comparison with the frequency detected in cycling
      cells of the bone marrow.
AB  - Monitoring the frequency of the Philadelphia (Ph) chromosome in chronic
      myelogenous leukemia (CML) is important in determining the effectiveness of
      treatment for patients during therapy. This can be done with high resolution by
      subjecting short-term bone marrow cultures (48 h) to 24 h of mitotic arrest
      before harvest and detecting Ph-positive (Ph+) metaphases by fluorescence in situ
      hybridization (FISH) in a procedure termed hypermetaphase FISH or HMF. Here, we
      compared procedures for detecting Ph+ interphase cells (interphase FISH or I
      FISH) in peripheral blood polymorphonucleocytes (PMNs) with HMF results on the
      bone marrow of the same 26 CML patients in different stages of remission. The
      probes for I-FISH in these experiments were relatively large (200-300 kb) and
      sufficiently resolved in PMNs so that 97.5% of the cells were scorable. The
      correlation between the frequencies of Ph+ cells from the two different cell
      sources was excellent (r = 0.983, P < 0.0001); however, there was a consistently
      higher level of Ph+ cells observed in the cycling marrow cells than in the
      peripheral blood PMNs. This was discussed in terms of current theories of
      apoptosis in CML cells. The large number of PMNs analyzable by I-FISH
      (approximately 500/patient in this study) provided sufficiently narrow 99%
      confidence intervals to suggest the procedure as an effective and efficient
      method for monitoring the frequency of Ph+ cells in CML patients undergoing
      therapy. However, for detection and quantification of minimal residual disease,
      HMF is preferable to I-FISH because of the much lower frequency of false-positive
      readings with the former procedure.

PMID- 9563880
TI  - Expression of the plasminogen activation system in kidney cancer correlates with
      its aggressive phenotype.
AB  - Malignant tumors contrast with benign ones in their ability to invade adjacent
      tissue and to metastasize. The urokinase plasminogen activator is a proteolytic
      enzyme that can facilitate these processes. In many carcinomas, the concentration
      of the urokinase plasminogen activator system is high. The high expression of
      these enzymes is related to tumor grade. In this study, we have investigated
      whether secretion of the urokinase plasminogen activator, urokinase plasminogen
      activator receptor, and plasminogen activator inhibitor 1 in normal kidney tissue
      and kidney cancer tissue follows this pattern. We have found that urokinase
      plasminogen activator, urokinase plasminogen activator receptor, and plasminogen
      activator inhibitor 1 were expressed in higher levels in kidney cancers (squamous
      cell carcinoma and renal cell carcinoma) than in normal kidney tissue and that
      these differences were statistically significant (P < or = 0.05). In renal cell
      carcinomas, we have observed differences between normal kidney tissue and renal
      cell carcinomas in males and Caucasians but not in females and African Americans
      (P < or = 0.05). Expression of the urokinase plasminogen activator system was
      also higher in grade III tumors when compared with lower-grade tumors or normal
      tissue.

PMID- 9563881
TI  - Analysis of colorectal cancer by comparative genomic hybridization: evidence for
      induction of the metastatic phenotype by loss of tumor suppressor genes.
AB  - Current models suggest that colon cancer initiation and progression are secondary
      to both the activation of oncogenes and the deletion of tumor suppressor genes.
      The role of each, however, is still poorly understood, particularly with regard
      to the induction of metastasis. We hypothesized that genetic differences exist
      between tumors that metastasize distantly and those that do not, and that
      oncogenes and tumor suppressor genes participate equally in this process. To
      address this hypothesis, human tumor specimens from localized [tumor-node
      metastasis (TNM) stage I-III] and primary colon cancers (n = 10) were directly
      compared with metastatic (TNM stage IV) lesions (n = 10) using comparative
      genomic hybridization analysis. Although several alterations were shared equally
      between primary tumors and metastases (+7q, +19q, and +20q), two patterns of
      distinguishing alterations were observed: (a) alterations that were more
      extensive in liver metastases than in primary tumors (+8q, +13q, -4p, -8p, -15q, 
      17p, -18q, -21q, and -22q); and (b) alterations that were unique to metastatic
      lesions (-9q, -11q, and -17q). Overall, genetic losses were more common than
      gains, and, more importantly, the number of losses/tumor was significantly higher
      for metastases than for primary tumors (9.3 + 1.3 versus 4.1 + 0.7; P = 0.00062,
      Wilcoxon's rank-sum test). The distinct predominance of genetic losses in the
      metastatic lesions when compared with the primary localized tumors provides
      evidence that the metastatic phenotype is induced by the deletion of tumor
      suppressor genes and permits the construction of physical maps targeting regions
      where novel tumor suppressor genes are likely to exist.

PMID- 9563882
TI  - An orthotopic model of human pancreatic cancer in severe combined immunodeficient
      mice: potential application for preclinical studies.
AB  - Pancreatic adenocarcinoma is one of the most incurable and least understood of
      all human cancers. It is the fourth leading cause of cancer-related mortality in
      males (after lung, prostate, and colon) and in females (after lung, breast, and
      colon) in the United States with <2-3% of patients surviving >5 years. In an
      attempt to search for more effective therapies for this disease, we report here,
      for the first time, an effective treatment, the combination of gemcitabine and
      auristatin-phenethylamine (PE), against an orthotopic implantation of a human
      pancreatic adenocarcinoma cell line (HPAC) in severe combined immunodeficient
      (SCID) mice. Tumor implantation was performed by injecting 100 microl of the HPAC
      cell suspension (1 x 10(6) cells) directly into the pancreas of 5-week-old SCID
      mice. After implantation, tumor formation was checked twice a week. All palpable
      tumors were detected within 21 days (100% take rate), and tumors were confirmed
      histologically to be pancreatic adenocarcinoma. For the subsequent efficacy
      trial, tumor-bearing SCID mice were randomized into four groups with five mice in
      each group. One served as a control, the second received gemcitabine alone (2.5
      mg/kg/injection i.p.), the third received auristatin-PE alone (2.0
      mg/kg/injection i.v.), and the fourth group received the combination of
      gemcitabine (i.p.) and auristatin-PE (1.5 mg/kg/injection i.v.). All animals were
      euthanized 7 days after the completion of their treatments, and the pancreases
      were resected. Histological examination revealed the tumors to be adenocarcinoma.
      The tumors were composed of diffuse sheets of cells interrupted by glandular
      spaces containing secretory material. Cytologically, the tumor cells were large,
      pleomorphic, and hyperchromatic. Many cells contained intracellular lumina
      containing mucin. Immunohistochemical studies showed strong p21WAF1 (p21)
      expression but no immunoreactivity with p53 and Her-2/neu antibodies. The mean
      pancreatic weight in the gemcitabine/auristatin-PE combination group was
      significantly (P = 0.014) lower (0.84 +/- 0.639 g) when compared with those of
      the control (2.91 +/- 1.19 g) and gemcitabine alone (1.84 +/- 0.796 g; P = 0.064)
      groups. In addition, the mean weight in the combination group approached
      statistical significance when compared with the auristatin-PE group alone (1.16
      +/- 0.635 g; P = 0.028). We conclude that the combination of gemcitabine and
      auristatin-PE is an effective treatment against HPAC tumors in this xenograft
      model and more effective than treatment with either gemcitabine or auristatin-PE
      alone and could be considered for future animal studies with pancreas cancer
      and/or for human clinical trials.

PMID- 9563883
TI  - Preclinical antitumor activity of an antibody against the leukocyte antigen CD48.
AB  - We have evaluated the antitumor activity of a murine antibody (IgG2a) against the
      leukocyte antigen CD48. CD48 is expressed on T and B lymphocytes, monocytes, and
      a wide range of lymphoid malignancies. To assess the therapeutic potential of an
      anti-CD48 antibody, we established a reproducible model of human B-cell (Raji)
      leukemia/lymphoma in C.B17/scid mice, where untreated mice develop hind leg
      paralysis due to tumor engraftment. Using this model, the murine anti-CD48
      antibody HuLy-m3 was shown to mediate a strong in vivo antitumor effect. Long
      term survival (>1 year) of scid mice was obtained after treatment with three 200
      microg i.v. doses of anti-CD48 antibody on days 0, 2, and 4 after i.v. injection
      of tumor cells. In contrast, mice treated with an isotype control antibody
      developed hind leg paralysis after 34 +/- 3 days. A strong antitumor response was
      still observed when a dose of 20 microg of HuLy-m3 antibody was used. During
      preclinical investigations, we also examined a number of properties of the CD48
      antigen. CD48 is present at high levels on the surface of T and B cells, but most
      (>95%) CD34-positive cells do not express CD48. Anti-CD48 antibodies are
      maintained on the surface of antigen-positive cells for extended periods (>24 h).
      These properties suggest that anti-CD48 antibodies may be useful in the treatment
      of a number of diseases including lymphoid leukemias and lymphomas.

PMID- 9563884
TI  - Cytotoxic activity of epidermal growth factor-genistein against breast cancer
      cells.
AB  - The receptor (R) for epidermal growth factor (EGF) is expressed at high levels on
      human breast cancer cells and associates with ErbB2, ErbB3, and Src proto
      oncogene family protein tyrosine kinases (PTKs) to form membrane-associated PTK
      complexes with pivotal signaling functions. Recombinant human EGF was conjugated
      to the soybean-derived PTK inhibitor genistein (Gen) to construct an EGF-R
      directed cytotoxic agent with PTK inhibitory activity. The EGF-Gen conjugate was
      capable of binding to and entering EGF-R-positive MDA-MB-231 and BT-20 breast
      cancer cells (but not EGF-R-negative NALM-6 or HL-60 leukemia cells) via its EGF
      moiety, and it effectively competed with unconjugated EGF for target EGF-R
      molecules in ligand binding assays. EGF-Gen inhibited the EGF-R tyrosine kinase
      in breast cancer cells at nanomolar concentrations, whereas the IC50 for
      unconjugated Gen was >10 microM. Notably, EGF-Gen triggered a rapid apoptotic
      cell death in MDA-MB-231 as well as BT-20 breast cancer cells at nanomolar
      concentrations. The EGF-Gen-induced apoptosis was EGF-R-specific because cells
      treated with the control granulocyte-colony stimulating factor-Gen conjugate did
      not become apoptotic. Apoptosis was dependent both on the PTK inhibitory function
      of Gen and the targeting function of EGF, because cells treated with unconjugated
      Gen plus unconjugated EGF did not undergo apoptosis. The IC50s of EGF-Gen versus
      unconjugated Gen against MDA-MB-231 and BT-20 cells in clonogenic assays were 30
      +/- 3 nM versus 120 +/- 18 microM (P < 0.001) and 30 +/- 10 nM versus 112 +/- 17
      microM (P < 0.001), respectively. Thus, the EGF-Gen conjugate is a >100-fold more
      potent inhibitor of EGF-R tyrosine kinase activity in intact breast cancer cells
      than unconjugated Gen and a >100-fold more potent cytotoxic agent against EGF-R+
      human breast cancer cells than unconjugated Gen. Taken together, these results
      indicate that the EGF-R-associated PTK complexes have vital antiapoptotic
      functions in human breast cancer cells and may therefore be used as therapeutic
      targets.

PMID- 9563885
TI  - Intracellular coexpression of epidermal growth factor receptor, Her-2/neu, and
      p21ras in human breast cancers: evidence for the existence of distinctive
      patterns of genetic evolution that are common to tumors from different patients.
AB  - Multiparameter flow cytometry studies were performed on cells from the primary
      tumors of 94 patients with breast cancer. Correlated cellular measurements of
      cell DNA content, Her-2/neu, epidermal growth factor receptor (EGFR), and p21ras
      levels were performed on each of 5,000 to 100,000 cells from each tumor. When
      criteria for positivity were matched with those in common use for
      immunohistochemical studies, 28 of 94 (30%) breast cancers were classified as
      positive for Her-2/neu overexpression. When similar criteria were applied to the
      EGFR measurements, 23 of 94 (24%) cases were classified as positive for EGFR
      overexpression. Similarly, 23 of 94 (24%) cases were classified as positive for
      p21ras overexpression. By conventional flow cytometric criteria for DNA ploidy,
      24 cases were diploid, 28 were tetraploid, and 42 were aneuploid. When the
      measurements were treated as separate sets of data, the only statistically
      significant correlations noted were the high frequency of diploid tumors, which
      did not overexpress any of the three oncogenes studied (P < 0.05), and an
      association between Her-2/neu overexpression and aneuploidy (P < 0.03). When the
      data were treated as correlated intracellular measurements, 90 of the 94 tumors
      studied contained a population of cells in which the intracellular levels of Her
      2/neu expression were directly correlated with the levels of EGFR expression in
      the same cells. The ratio of Her-2/neu molecules to EGFR molecules in the same
      cells exceeded 1 in the majority of tetraploid and aneuploid cases and was close
      to or less than 1 in the majority of diploid cases. In nearly all tumors, p21ras
      overexpression was observed only in cells that overexpressed Her-2/neu, EGFR, or
      both, and p21ras levels per cell were more closely correlated with levels of EGFR
      per cell in the same cells than with Her-2/neu levels per cell. The data are
      consistent with a model in which heterodimerization of Her-2/neu and EGFR in
      individual cells is achieved by one of several genetic evolutionary pathways, all
      of which commonly lead to p21ras overexpression. The two major genetic
      evolutionary pathways identified in this study are an aneuploid, Her-2/neu
      overexpression-driven pathway seen in 59 of 94 tumors, and a diploid, EGFR
      overexpression-driven pathway seen in 19 of 94 tumors. All tumors with Her
      2/neu:EGFR ratios greater than 2 contained an infiltrating ductal carcinoma
      component, whereas all infiltrating pure lobular carcinomas had Her-2/ neu:EGFR
      ratios that were less than 2. All of the genetic evolutionary pathways identified
      in this study were represented among the 11 tumors from patients who experienced
      early tumor recurrences.

PMID- 9563886
TI  - Phase II and pharmacodynamic studies of pyrazine diazohydroxide (NSC 361456) in
      patients with advanced renal and colorectal cancer.
AB  - Pyrazine diazohydroxide (PZDH) is a novel antitumor agent that forms DNA adducts
      via the reactive pyrazine diazonium ion. In a recent Phase I study of PZDH, we
      identified a recommended Phase II dose of 100 mg/m2/day x 5, given as a 5-min
      i.v. bolus with the cycles repeated every 42 days (N. J. Vogelzang, et al, Cancer
      Res., 54: 114-119, 1994). There was a moderate negative correlation between serum
      chloride concentration and logarithm platelet nadir, suggesting the hypothesis
      that PZDH is activated in an acidic environment, leading to more toxicity in
      acidotic patients. Therefore, the University of Chicago Phase II cooperative
      network conducted two Phase II studies of PZDH in renal cancer (15 patients, 2
      with liver metastases) and in 5-fluorouracil-refractory colorectal cancer (14
      patients, 13 with liver metastases) to determine efficacy in each disease and to
      correlate safety and tolerance of the drug with PZDH
      pharmacokinetics/pharmacodynamics and with arterial blood gas measurements. There
      were no responses seen in either tumor type. The primary toxicity of PZDH was
      myelosuppression with neutropenia (absolute neutrophil count, < 1000/microl) and
      thrombocytopenia (<50,000 cells/microl), seen in 41 and 24% of all cycles,
      respectively. Other grade 3 and 4 toxicities were rare. Pharmacodynamic analysis
      revealed no significant correlation between plasma levels at 5, 60, and 120 min;
      WBCs; absolute neutrophil and platelet count nadirs; and initial serum chloride
      or blood pH levels. The colorectal patients experienced significantly more
      thrombocytopenia than did the renal cancer patients (median platelet nadir after
      cycle 1 was 151 x 10(3)/microl for renal patients versus 76 x 10(3)/microl for
      colon patients; P = 0.04), suggesting either that prior 5-fluorouracil and
      leucovorin reduced bone marrow reserve or that colorectal patients with liver
      metastases experienced more PZDH toxicity. Regression analyses revealed a
      possible relationship (P = 0.06) between serum pH and thrombocytopenia (i.e., for
      each increase of 0.03 in pH, there was a 34% increase in the platelet nadir), but
      there was no relationship between serum chloride and thrombocytopenia. Curiously,
      an increase in alkaline phosphatase was associated with an increase in the
      platelet nadir (P = 0.02). If PZDH continues to be developed as an antineoplastic
      agent, further studies of these relationships are suggested.

PMID- 9563887
TI  - Prospective randomized trial of 5-fluorouracil versus 5-fluorouracil plus
      levamisole in the treatment of metastatic colorectal cancer: a Hoosier Oncology
      Group trial.
AB  - The purpose of this study was to compare the objective response rate, duration of
      remission, and survival of 5-fluorouracil (5-FU) versus those of 5-FU plus
      levamisole in metastatic colorectal cancer using the same dose and schedule of
      these agents as in the North Central Cancer Treatment Group and intergroup
      studies of adjuvant therapy. Patients with no prior history of chemotherapy for
      metastatic disease were entered on this Hoosier Oncology Group randomized Phase
      III trial. Patients were stratified by Karnofsky performance status and presence
      or absence of liver metastases. They were randomized to receive 450 mg/m2 5-FU
      i.v. for 5 days followed by 15 mg/kg i.v. weekly (arm 1) or the same dose of 5-FU
      plus levamisole 50 mg p.o. every 8 h for 3 days every 2 weeks (arm 2). The
      duration of treatment for both arms was 26 weeks. From April 1990 to March 1995,
      199 patients were entered. One hundred eighty-two patients, 91 in each arm, were
      fully evaluable. The response rates were 12% on arm 1 and 13% on arm 2. The
      median duration of response was 18 weeks on both arms. The median survival was 48
      weeks on arm 1 and 41 weeks on arm 2 (P = 0.20). This study failed to show any
      improvement in survival, response, or duration of remission with the addition of
      levamisole to 5-FU in the treatment of metastatic colorectal cancer.

PMID- 9563888
TI  - Effect of food on the pharmacokinetics of capecitabine and its metabolites
      following oral administration in cancer patients.
AB  - Capecitabine (Ro 09-1978) is a novel oral fluoropyrimidine carbamate that was
      rationally designed to generate 5-fluorouracil (5-FU) selectively in tumors. The
      effect of food on the pharmacokinetics of capecitabine and its metabolites was
      investigated in 11 patients with advanced colorectal cancer using a two-way cross
      over design with randomized sequence. Patients received repeated doses of 666 or
      1255 mg/m2 of capecitabine twice daily. On study days 1 and 8, drug was
      administered following an overnight fast or within 30 min after consumption of a
      standard breakfast, and serial blood samples were collected. Concentrations of
      capecitabine and its metabolites [5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5
      fluorouridine (5'-DFUR), 5-FU, dihydro-5-fluorouracil (FUH2), and alpha-fluoro
      beta-alanine (FBAL)] in plasma were determined by high-performance liquid
      chromatography or liquid chromatography/mass spectroscopy. Intake of food prior
      to the administration of capecitabine resulted in pharmacokinetic changes of all
      compounds involved. The extent of these changes, however, varied considerably
      between the various compounds. Maximum plasma concentration (Cmax) and area under
      the plasma concentration-time curve (AUC) values were decreased after food, and
      time until the occurrence of Cmax values were increased. In contrast, the
      apparent elimination half-life was not affected by food intake. The extent of
      change in Cmax and AUC was highest for capecitabine and decreased with the order
      of formation of the metabolites. The "before:after food" ratios of the Cmax
      values were 2.47 for capecitabine, 1.81 for 5'-DFCR, 1.53 for 5'-DFUR, 1.58 for 5
      FU, 1.26 for FUH2, and 1.11 for FBAL. The before: after food ratios of the AUC
      values were 1.51 for capecitabine, 1.26 for 5'-DFCR, 1.15 for 5'-DFUR, 1.13 for 5
      FU, 1.07 for FUH2, and 1.04 for FBAL. The results show that food has a profound
      effect on the AUC of capecitabine, a moderate effect on the AUC of 5'-DFCR, and
      only a minor influence on the AUC of the other metabolites in plasma. In
      addition, a profound influence on Cmax of capecitabine and most of its
      metabolites was found. Detailed information on the relationship between
      concentration and safety/efficacy is necessary to evaluate the clinical
      significance of these pharmacokinetic findings. At present, it is recommended
      that capecitabine be administered with food as this procedure was used in the
      clinical trials.

PMID- 9563889
TI  - Dynamic T1-weighted magnetic resonance imaging and positron emission tomography
      in patients with lung cancer: correlating vascular physiology with glucose
      metabolism.
AB  - The management of primary lung cancer relies on sophisticated imaging methods to
      assist in the diagnosis, staging, and evaluation of tumor regression during
      treatment. The information provided is generally anatomical in nature, except for
      that provided by positron emission tomography with [18F]fluorodeoxyglucose, a
      modality that yields physiological data that have been shown to be useful in
      identifying neoplasia, based on an elevated glucose metabolic rate. Because the
      metabolism of malignant tissue depends intimately on neovascularization to
      provide oxygen and glucose in sufficient quantities to allow tumor growth, the
      characterization of tumor vascular physiology could be an important tool for
      assessing and predicting the likely effectiveness of treatment. Our goal was to
      show the feasibility and practical value of parameters of tumor vascular
      physiology obtained using dynamic T1-weighted magnetic resonance imaging (MRI),
      to correlate them with glucose metabolism and to demonstrate changes in these
      parameters during and after treatment in patients with lung cancer. Parameters of
      vascular physiology [permeability-surface area (PS) product and extracellular
      contrast agent distribution volume] and glucose metabolism were assessed in 14
      patients with lung cancer. Glucose metabolism was measured by using
      [18F]fluorodeoxyglucose-positron emission tomography. Vascular physiology was
      assessed by dynamic T1-weighted, contrast-enhanced MRI. The mean PS product in
      tumor was 0.0015 +/- 0.0002 s(-1) (n = 13) before, 0.0023 +/- 0.0003 s(-1) (n =
      3, P = 0.053) midway through, and 0.00075 +/- 0.0002 s(-1) (n = 5, P < 0.03) 2
      weeks after treatment. Values for the extracellular contrast distribution space
      were 0.321 +/- 0.03 before, 0.289 +/- 0.02 midway through, and 0.195 +/- 0.02 (P
      < 0.01) 2 weeks after therapy. The glucose metabolic rate was significantly
      correlated with the PS product (P < 0.01) but not with the extracellular contrast
      distribution space. Our results demonstrate that tumor PS product correlates with
      glucose metabolism, that chemo- and radiotherapy induce observable and
      quantifiable changes in these parameters, and that such changes can be measured
      by in vivo dynamic MRI. Quantitative dynamic T1-weighted MRI of tumor vascular
      physiology may have a useful role in the clinical management of lung cancer.

PMID- 9563890
TI  - Idiotypic protein-pulsed adherent peripheral blood mononuclear cell-derived
      dendritic cells prime immune system in multiple myeloma.
AB  - Adherent peripheral blood mononuclear cell-derived dendritic cells pulsed with
      autologous idiotypic protein (Id) were given to a patient with advanced-stage
      refractory myeloma. Potentially beneficial antimyeloma Id-specific immune
      responses were produced, characterized by MHC-dependent T-cell-proliferative
      responses with cytokine release and the production of anti-Id antibodies. A T
      cell line generated after vaccination was also able to lyse autologous Id-pulsed
      targets and recognize fresh autologous myeloma cells. The immune responses were
      associated with a transient minor fall in the serum Id level and were not ablated
      by high-dose myeloablative chemotherapy. This report therefore demonstrates the
      clinical use of adherent peripheral blood mononuclear cell-derived dendritic
      cells for vaccination in cancer and the persistence of immune responses after
      high-dose chemotherapy. Such a therapeutic approach may be useful in reducing the
      relapse rate in patients who have minimal residual disease after chemotherapy.

PMID- 9563891
TI  - Elevated levels of versican but not decorin predict disease progression in early
      stage prostate cancer.
AB  - Patients with clinically localized prostate cancer who might be cured by
      aggressive management are not easily identified using current clinical
      information. Additional, more accurate, biomarkers of tumor behavior need to be
      identified to improve clinical outcome. Our previous studies indicated that the
      concentration of the glycosaminoglycan chondroitin sulfate in prostatic stroma
      might be a useful biomarker of disease progression in early-stage prostate
      cancer. In this study, two chondroitin sulfate proteoglycans, versican and
      decorin, were investigated. Versican and decorin were immunolocalized to the
      periacinar and peritumoral fibromuscular stroma in sections of nonmalignant and
      malignant human prostate tissues. Video image measurements indicated that the
      concentrations of both proteoglycans were increased in the prostatic tissue of
      men with early-stage prostate cancer compared with tissue from men without cancer
      (P = 0.0006). Cox's univariate analysis indicated that increases in versican
      concentration but not in that of decorin were associated with increased risk of
      prostate-specific antigen (PSA) progression. Versican concentration was compared
      with other clinical or biological features of prognosis in two-variable
      regression analyses. Versican and serum PSA concentrations were independent
      predictors of PSA progression. Versican was a stronger prognostic factor than
      tumor grade, and it could predict outcome for patients with moderately
      differentiated tumors. Patients with low versican concentration had significantly
      better progression-free survival than patients with high levels of versican
      (Kaplan-Meier plot, 89% versus 27% PSA progression-free at 5 years, respectively;
      P = 0.0001). We conclude that the measurement of prostatic concentrations of
      versican, a molecule with reported anticellular adhesive properties, may be a
      useful marker of disease progression in patients with early-stage prostate cancer
      and that further study of versican in other patient cohorts is warranted.

PMID- 9563892
TI  - Loss of heterozygosity on chromosome 18q in cohesive-type gastric cancer is
      associated with tumor progression and poor prognosis.
AB  - Although loss of heterozygosity (LOH) on chromosome 18q is frequently found in
      gastric cancer, the clinical significance of this abnormality has not been well
      documented. We examined LOH on chromosome 18q22-23 in DNA extracted from the
      tissues of gastric cancer patients using the PCR-based dinucleotide repeat assay
      with two microsatellite markers, D18S61 and D18S58. We investigated LOH in 100
      samples of DNA extracted from formalin-fixed, paraffin-embedded tissues of
      cohesive-type gastric cancer patients operated on between 1984 and 1993. Thirty
      two of 83 informative cases (39%) showed LOH on chromosome 18q22-23 at one or two
      loci. The LOH correlated significantly with serosal invasion of the tumor (P =
      0.004) and hematogenous recurrence (P = 0.035). In 60 cases who were cured, the 5
      year survival rate in patients with LOH (54%) was lower than that in patients
      without LOH (81%; P = 0.019). These results suggest that 18q22-23 LOH in cohesive
      gastric cancer is associated with tumor progression and a patient's poor
      prognosis.

PMID- 9563893
TI  - Presence of human papilloma virus DNA in pelvic lymph nodes can predict
      unexpected recurrence of cervical cancer in patients with histologically negative
      lymph nodes.
AB  - Patients without any evidence of lymph node metastases are supposed to have a
      fair prognosis, but some of these patients develop recurrent disease unexpectedly
      after surgery. The object of this study is to examine whether the detection of
      human papilloma virus (HPV) DNA could be used as a diagnostic marker to predict
      such recurrences. Two hundred and thirty-six patients undergoing radical
      hysterectomy and pelvic lymphadenectomy for stage Ib and II cervical cancer at
      Okayama University Hospital (Japan) from 1988-1994 were reviewed, and only those
      cases positive for HPV-16 or HPV-18 in primary sites were included in this
      survey. The E6-E7 region of the HPV genome was amplified by a sensitive nested
      PCR from archival pelvic lymph node specimens. HPV sequences identical to those
      of the primary sites were detected in histologically confirmed negative lymph
      nodes, regardless of histological type or HPV type of the primary lesion, in 9 of
      10 patients who recurred within 4 years of surgery. In contrast, histologically
      confirmed negative lymph nodes from 12 patients with stage IIb disease without
      evidence of recurrent disease were all negative for the presence of HPV, except
      for 1 lymph node. The presence of HPV DNA in histologically negative nodes
      implies the possibility of early nodal involvement or coexistence of undetectable
      hematogenic dissemination and could therefore be used as a diagnostic marker to
      predict the unexpected recurrence of these patients.

PMID- 9563894
TI  - Batimastat, a synthetic inhibitor of matrix metalloproteinases, potentiates the
      antitumor activity of cisplatin in ovarian carcinoma xenografts.
AB  - Batimastat (also known as BB-94) is a synthetic matrix metalloproteinase
      inhibitor that has shown antineoplastic and antiangiogenic activity in various
      tumor models. In this study, two human ovarian carcinoma (HOC) xenografts (HOC22
      and HOC8) were used to investigate the effect of batimastat on the antineoplastic
      activity of cisplatin. Both xenografts produced ascites and solid lesions in the
      peritoneal cavity of nude mice. HOC cells were inoculated i.p. in nude mice, and
      treatment was started at different stages of the disease. Batimastat was
      administered alone or concurrently with or subsequent to cisplatin therapy. In
      all of the protocols, the response of HOC xenografts was confirmed by cytological
      analysis of ascites and histological examination of the organs in the peritoneal
      cavity. Treatment of nude mice bearing early-stage (3 days after tumor
      implantation) HOC22 or HOC8 with cisplatin or batimastat alone delayed tumor
      growth and increased the survival time of the mice, although all animals
      eventually died. In contrast, treatment with batimastat (60 mg/kg i.p. every
      other day, for a total of eight injections) concomitantly with cisplatin (4 mg/kg
      i.v., every 7 days for a total of three injections) completely prevented growth
      and spread of both xenografts, and all animals were alive and healthy on day 200.
      The potentiation of cisplatin's activity by batimastat was dose dependent and was
      observed in the treatment of both advanced (7 days after tumor inoculation) and
      late-stage (20 days after inoculation) tumor. The administration of batimastat
      following cisplatin therapy also led to significant improvement in the survival
      of mice compared to treatment with cisplatin alone. These results suggest a
      potentiation of the antineoplastic activity of cisplatin by batimastat and
      support the use of the two agents in combination in the treatment of ovarian
      cancer patients.

PMID- 9563895
TI  - Recombinant heregulin-Pseudomonas exotoxin fusion proteins: interactions with the
      heregulin receptors and antitumor activity in vivo.
AB  - Growth factor receptors provide unique opportunities for development of targeted
      anticancer therapy. Members of the type I receptor tyrosine kinase family,
      including epidermal growth factor (EGF) receptor (EGFR) and ErbB-2/neu, are often
      overexpressed in various human cancer cells, including breast. Recently, it has
      been shown that both ErbB-3 and ErbB-4 are receptors for heregulin (HRG)/Neu
      differentiation factor. Eight chimeric toxins composed of the extracellular and
      EGF-like domains of four different HRG isoforms and truncated Pseudomonas
      exotoxin (PE38KDEL) were constructed. The fusion proteins exhibited activity
      similar to the native HRG in inducing ErbB receptors phosphorylation. The EGF
      like domain of HRG13 and HRGbeta2 fused to PE38KDEL showed the highest cytotoxic
      activity, with a IC50 of < or = 0.001 ng/ml. The alpha isoforms that were fused
      to PE38KDEL were 100-fold less active than the beta isoforms. The HRG-Pseudomonas
      exotoxin (PE) toxins show extremely high activity against cells expressing ErbB-4
      receptor, alone or together with other members of the ErbB receptor family. Cells
      that do not express ErbB-4 but express ErbB-3 receptor, together with the ErbB-2
      or EGFR, exhibited moderate sensitivity to HRG-PE toxins. HRG-PE toxins have
      little or no activity against cells expressing EGFR, ErbB-2, or ErbB-3 alone.
      More than an 80% tumor regression was achieved by intratumor injection of 1
      microg of fusion proteins per day for 5 days. Continuous i.p. administration of
      EGF-like domain of HRGbeta1-PE38KDEL for 7 days via a miniosmotic pump at a dose
      of 40 microg/kg/day inhibited the growth of ErbB-4 receptor positive but not ErbB
      4 receptor negative cell lines in athymic nude mice. We conclude that there is
      therapeutic potential of HRG-PE toxins in the therapy of cancers overexpressing
      the ErbB-4 or ErbB-2 plus ErbB-3 receptors.

PMID- 9563896
TI  - Induction of sensitivity to doxorubicin and etoposide by transfection of MCF-7
      breast cancer cells with heregulin beta-2.
AB  - HER2 (erbB-2) proto-oncogene amplification and/or overexpression correlate with
      poor prognosis in many malignancies. The precise biological role of this
      oncogenic signaling pathway (which also involves the HER4 gene) in breast cancer
      is unclear. One property conferred by this oncogene relates to response to drug
      therapy. Clinical studies support an association between HER2 overexpression and
      resistance to alkylating agents (cisplatinum and cyclophosphamide). Data from the
      Cancer and Leukemia Group B 8869/8541 study indicate enhanced dose responsiveness
      to doxorubicin (Adriamycin) in patients who overexpress the HER2 receptor.
      Heregulin beta-2, a naturally occurring ligand that activates the HER2 receptor
      by inducing its heterodimerization with the HER4 receptor, has recently been
      cloned. The ability of this ligand to phosphorylate the HER2 receptor exogenously
      allows us to study the effect of HER2 activation on cancer cell behavior. To
      study the relationship between chemotherapy response and activation of HER2, MCF
      7 cells expressing biologically active heregulin were assessed for response to
      doxorubicin and etoposide, both of which are topoisomerase IIalpha (topo IIalpha)
      inhibitors. Several clones show markedly increased sensitivity to these drugs. In
      addition, the same wild-type MCF-7 cells transfected with heregulin beta-2 under
      the control of an inducible promoter also show this dose-response relationship to
      doxorubicin after the expression of heregulin beta-2 is activated by zinc. The
      modulation of topo IIalpha was studied in the cell lines transfected with
      heregulin. topo IIalpha mRNA and protein (total protein and enzymatic
      decatenating activity) were found to be up-regulated in heregulin beta-2
      transfected cells. Moreover, topo IIalpha promoter activity was also modestly
      increased in heregulin beta-2-transfected cells. Because up-regulation of topo
      IIalpha in vitro and in clinical specimens is associated with increased response
      to doxorubicin (presumptively by an increase in drug substrate), this may be the
      mechanism of the increased sensitivity to doxorubicin seen in heregulin beta-2
      transfected cells. This implies that activation of HER2 or one of the other
      members of the receptor family may increase sensitivity to doxorubicin by up
      regulation of topo IIalpha. This finding suggests the use of receptor/ligand
      expression to direct patient-specific therapeutic choices (e.g., doxorubicin
      versus alkylator-based regimens) and the use of biological agents (such as
      heregulin) in combination with certain chemotherapeutic agents to enhance
      response to treatment in breast cancer patients.

PMID- 9563897
TI  - Induction of thymidine phosphorylase activity and enhancement of capecitabine
      efficacy by taxol/taxotere in human cancer xenografts.
AB  - Thymidine phosphorylase (dThdPase) is an essential enzyme for the activation of
      the cytostatics capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine)
      and its intermediate metabolite [5'-deoxy-5-fluorouridine (5'-dFUrd)] to 5
      fluorouracil in tumors. We have tried to identify the best partners of
      capecitabine in combination therapy, such as dThdPase up-regulators, which may
      enhance the efficacy of this compound. Among various cytostatics studied with the
      WiDr human colon cancer xenograft model, Taxol, Taxotere, and mitomycin C greatly
      increased levels of human dThdPase in tumors, and cyclophosphamide slightly
      increased the enzyme level. These cytostatics simultaneously increased the levels
      of human tumor necrosis factor alpha (TNFalpha), which is an up-regulator of
      dThdPase. In cultures of the WiDr cells, however, Taxol did not up-regulate
      TNFalpha to a detectable level and only slightly enhanced levels of dThdPase.
      These results suggest that Taxol might indirectly elevate TNFalpha in tumor
      cells, which in turn up-regulated dThdPase in the tumor cells in the WiDr cancer
      xenograft. In the combination therapy, the efficacy of Taxol and Taxotere with
      either capecitabine or 5'-dFUrd was more than just additive. In contrast, Taxol
      and either 5-fluorouracil or UFT (a mixture of tegafur and uracil) in combination
      showed only additive activity. Taxol and Taxotere might enhance the efficacy of
      capecitabine and 5'-dFUrd, probably by modulating dThdPase activity in tumor
      tissues.

PMID- 9563898
TI  - Activity of oxaliplatin against human tumor colony-forming units.
AB  - This study was conducted to identify tumor types warranting Phase II clinical
      trials of oxaliplatin using the human tumor cloning assay. Oxaliplatin was tested
      at concentrations ranging from 0.5 to 50.0 microg/ml in 1-h and 14-day continuous
      exposures along with 1.4 microg/ml carboplatin and 0.2 microg/ml cisplatin for
      comparison. We defined in vitro response as tumor growth inhibition >50% of
      control. In the 1-h exposure schedule, in vitro responses were observed in 9 of
      116 (8%), 18 of 115 (16%), 38 of 103 (37%), and 7 of 13 (54%) tumor specimens at
      concentrations of 0.5, 5.0, 10.0, and 50.0 microg/ml oxaliplatin, respectively.
      In the 14-day exposure schedule, in vitro responses were observed in 10 of 121
      (8%), 37 of 121 (31%), 57 of 106 (54%), and 15 of 15 (100%) tumor specimens at
      concentrations of 0.5, 5.0, 10.0, and 50.0 microg/ml oxaliplatin, respectively.
      Activity was observed against colon cancer, non-small cell lung cancer, gastric
      cancer, and melanoma colony-forming units. In both cisplatin-resistant and
      cisplatin-sensitive tumors, the activity of oxaliplatin was concentration and
      time dependent. A 1-h exposure to 5.0 and 10.0 microg/ml oxaliplatin led to 7.4
      and 23.4% in vitro responses, respectively, in specimens resistant to 1-h
      exposure of 0.2 microg/ml cisplatin. Moreover, 1-h exposures to 5.0 microg/ml and
      10.0 microg/ml oxaliplatin showed in vitro antitumor responses in 10.2 and 24.3%,
      17.2 and 34.5%, 10.0 and 20.0%, 6.7 and 16.7%, and 11.4 and 34.3% of specimens
      resistant to 1.4 microg/ml carboplatin, 6.0 microg/ml 5-fluorouracil, 3.0
      microg/ml irinotecan, 10.0 microg/ml paclitaxel, and 0.04 microg/ml doxorubicin,
      respectively. The effect in those drug-resistant specimens was improved when
      oxaliplatin was used on the protracted exposure regimen. Our data indicate that
      oxaliplatin is an active drug in vitro against a large variety of human tumors.
      Both concentration and duration of exposure are important factors for oxaliplatin
      cytotoxicity. The broad spectrum of activity and the in vitro activity against
      some tumors primarily resistant to conventional anticancer drugs encourage
      further clinical investigations of oxaliplatin in patients with advanced cancer
      refractory to conventional chemotherapy.

PMID- 9563899
TI  - Impairment of the actin-myosin interaction in permeabilized cardiac trabeculae
      after chronic doxorubicin treatment.
AB  - The development of chronic cardiotoxicity in cancer patients treated with
      doxorubicin (DOX) and other anthracycline antineoplastic agents is a major dose
      limiting factor. In a previous study, we demonstrated an acute effect of
      anthracyclines on the actin-myosin contractile system. Here, we report chronic
      effects of DOX both on the contractile system and on the function of the
      sarcoplasmic reticulum (SR). Male Wistar rats were treated with DOX (2 mg/kg,
      i.v., once a week for 4 weeks), whereas control rats received equal volumes of
      saline. Right ventricular trabeculae were isolated and skinned by exposure to
      Triton X-100 or saponin at 1, 2, 4, and 6 weeks after the final DOX
      administration. The maximal tension of trabeculae was similar between DOX-treated
      and control animals at 1 week posttreatment. At 2, 4, and 6 weeks posttreatment,
      the maximal tension of trabeculae of DOX-treated animals was significantly
      decreased by 27, 32, and 37%, respectively (P < 0.01). The rigor tension in
      trabeculae of DOX-treated animals was similar at 1 week posttreatment but
      significantly decreased at 2, 4, and 6 weeks posttreatment (by 25, 25, and 37%,
      respectively; P < 0.01). The ratio between rigor tension and maximal tension was
      significantly higher in DOX-treated groups as compared to controls (0.39 +/- 0.01
      and 0.36 +/- 0.01; P < 0.05). Calcium sensitivity of DOX-treated preparations was
      significantly decreased as compared to controls (5.59 +/- 0.02 and 5.65 +/- 0.01;
      P < 0.05), whereas no effects were found on the cooperativity of the regulatory
      proteins, as measured by the Hill coefficient. The calcium release function of
      the SR, measured by caffeine (25 mM) stimulation in saponin-skinned trabeculae,
      was the same in DOX-treated and control groups at all posttreatment periods. The
      results of the present study show that long-term DOX treatment causes substantial
      impairment of the cross-bridge interaction in skinned trabeculae, which is
      reflected by a progressive attenuation of the contractile performance. The
      function of the SR, however, remains unaffected by DOX treatment in our
      preparations. The direct effect of chronic DOX treatment on the actin-myosin
      system provides an additional mechanism through which anthracyclines exert their
      cardiotoxic effects and may facilitate the development of cardioprotective
      strategies.

PMID- 9563900
TI  - Interleukin 6 differentially potentiates the antitumor effects of taxol and
      vinblastine in U266 human myeloma cells.
AB  - Newer therapeutic strategies for the treatment of multiple myeloma have focused
      on antagonizing the growth-promoting functions of interleukin 6 (IL-6). In this
      study, we examined the antitumor effects of two mechanistically different
      microtubule poisons, Taxol and vinblastine, in U266 human myeloma cells and
      determined whether IL-6 altered these effects. Taxol and vinblastine led to a
      dose-dependent inhibition of [3H]thymidine incorporation and altered the DNA
      distribution pattern of U266 cells. Both drugs led to an increase in the
      proportion of cells in the sub-G1 fraction (<2N DNA). However, at the IC50
      concentration, vinblastine, but not Taxol, increased the percentage of cells in
      the G2-M phase of the cell cycle. In the presence of IL-6, the DNA distribution
      pattern induced by Taxol or vinblastine was altered. Whereas IL-6 augmented the
      sub-G1 fraction and G2-M phase for Taxol-treated cells, only the G2-M phase was
      increased for vinblastine-treated cells. Furthermore, IL-6 enhanced the
      cytotoxicity of both drugs, which became evident only during recovery in cytokine
      free and drug-free medium. However, the cytotoxicity of Taxol was augmented to a
      significantly greater extent than that of vinblastine (P < 0.001). Immunostaining
      with antibodies to alpha-tubulin and mitogen-activated protein kinase revealed
      colocalization of these two proteins within microtubule asters. In the presence
      of IL-6, the number of cells containing microtubule asters increased for Taxol
      treatment, but not for vinblastine treatment. These data indicate that IL-6 leads
      to differential modulation of the cytotoxicity of Taxol and vinblastine in U266
      cells. Whereas recruitment of cells in the S phase of the cell cycle represents a
      major mechanism by which IL-6 potentiates the cytotoxicity of vinblastine,
      augmentation of the cytotoxicity of Taxol involves additional mechanisms.
      Furthermore, our data suggest that the microtubule-associated form of mitogen
      activated protein kinase may play a role in IL-6-mediated enhancement of the
      cytotoxicity of Taxol. The clinical implications of these findings are discussed.

PMID- 9563901
TI  - Disruption of p53 function in immortalized human cells does not affect survival
      or apoptosis after taxol or vincristine treatment.
AB  - In the present study, we report our findings on the impact of p53 disruption on
      the sensitivity of human cell lines to the antimitotic agents Taxol and
      vincristine. Comparisons of cell survival and apoptosis were made with y
      irradiation and, in some cases, several other DNA-damaging chemotherapeutic
      agents. Studies in eight Burkitt's lymphoma and lymphoblastoid cell lines (four
      wild-type p53 and four mutant p53 cell lines) revealed that the DNA-damaging
      agents assayed tended to exhibit less growth inhibition in the mutant p53 cell
      lines compared to the wild-type p53 cell lines. In contrast, no significant
      correlation was apparent between p53 gene status and the growth-inhibitory
      potency of Taxol or vincristine in these eight cell lines. We also found that
      contrary to gamma-irradiation, Taxol and vincristine could induce apoptosis in
      lymphoma cell lines harboring p53 mutations. These observations were explored
      further in lymphoblastoid VDSO cells (wild-type p53) from a normal individual and
      stably transfected VDSO derivatives lacking p53 function due to expression of the
      human papillomavirus type-16 E6 gene. We found that p53 disruption in VDSO/E6
      cells blocked y-ray-induced apoptosis and afforded a survival advantage to
      VDSO/E6 cells compared to control-transfected cells. In contrast, p53 disruption
      did not affect Taxol- or vincristine-induced apoptosis or survival in VDSO cells.
      The effect of p53 disruption on Taxol sensitivity was explored further in the
      breast carcinoma MCF-7 and colon carcinoma HCT-116 cell lines that had been
      stably transfected with either the human papillomavirus type-16 E6 gene or a
      dominant-negative mutant p53 gene. Again, in these cell model systems, we found
      that p53 disruption did not affect the growth-inhibitory potency of Taxol. Taken
      together, our results suggest that p53 status is not a dominant factor in the
      mechanism by which antimitotic agents induce apoptosis and reduce survival in
      immortalized human cell lines.

PMID- 9563902
TI  - Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast
      cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21
      concomitant with a decrease in kinase activity of cyclin-dependent kinases and
      associated cyclins.
AB  - There is an increasing interest in identifying potent cancer preventive and
      therapeutic agents against breast cancer. Silymarin, a flavonoid antioxidant
      isolated from milk thistle, exerts exceptionally high to complete
      anticarcinogenic effects in tumorigenesis models of epithelial origin. In this
      study, we investigated the anticarcinogenic effect of silymarin and associated
      molecular mechanisms, using human breast carcinoma cells MDA-MB 468. Silymarin
      treatment resulted in a significantly high to complete inhibition of both
      anchorage-dependent and anchorage-independent cell growth in a dose- and time
      dependent manner. The inhibitory effects of silymarin on cell growth and
      proliferation were associated with a G1 arrest in cell cycle progression
      concomitant with an induction of up to 19-fold in the protein expression of
      cyclin-dependent kinase (CDK) inhibitor Cip1/p21. Following silymarin treatment
      of cells, an incremental binding of Cip1/p21 with CDK2 and CDK6 paralleled a
      significant decrease in CDK2-, CDK6-, cyclin D1-, and cyclin E-associated kinase
      activity with no change in CDK2 and CDK6 expression but a decrease in G1 cyclins
      D1 and E. Taken together, these results suggest that silymarin may exert a strong
      anticarcinogenic effect against breast cancer and that this effect possibly
      involves an induction of Cip1/p21 by silymarin, which inhibits the threshold
      kinase activities of CDKs and associated cyclins, leading to a G1 arrest in cell
      cycle progression.

PMID- 9563904
TI  - The BAX gene, the promoter of apoptosis, is mutated in genetically unstable
      cancers of the colorectum, stomach, and endometrium.
AB  - Disruption of the DNA mismatch repair system, characterized by microsatellite
      instability (MI), plays an important role in the course of human carcinogenesis
      by increasing the rate of mutations of genes associated with cancers. However, it
      is not clear which genes are the target genes for mutation in the course of
      carcinogenesis. Microsatellites within the coding region of the transforming
      growth factor beta receptor type II (RII) and insulin-like growth factor II
      receptor (IGF-IIR) genes were reported to be targets for mutation during the
      course of carcinogenesis in MI+ tumors. Recently, somatic mutations were found in
      a poly(G)8 tract in the BCL-2-associated X protein (BAX) gene, one of the
      essential players in apoptosis, in some MI+ tumors. We examined mutations of BAX
      in MI+ cancers of various organs and found frameshift mutations at the poly(G)8
      tract in 5 of 15 (33%) gastric cancers, 3 of 26 (12%) endometrial cancers, and 9
      of 22 (41 %) colorectal cancers. In contrast, no such mutations were found in
      pancreatic cancer. These results suggest that mutations of BAX play an important
      role in the course of carcinogenesis in the stomach, colorectum, and endometrium.

PMID- 9563903
TI  - Infrequent mutation of the p16/MTS1 gene and overexpression of cyclin-dependent
      kinase 4 in human primary soft-tissue sarcoma.
AB  - The pl6INK4a/MTS1 (p16) gene encodes a specific inhibitor of cyclin-dependent
      kinase (CDK)4 and CDK6. The p16 gene is frequently mutated or deleted in many
      types of cancer cell lines as well as in certain types of primary tumors. p16
      knockout mice are viable but predisposed to sarcoma and B-cell lymphoma. To
      investigate the role of p16 in human soft-tissue sarcoma tumor progression, we
      examined the p16 gene by Southern blot analysis and PCR sequencing in 30 pairs of
      primary soft-tissue sarcomas and autologous normal tissue. Only one tumor sample
      showed possible rearrangement of the p16 gene. In contrast, Western blot analysis
      of the p16 protein in 20 pairs of samples showed decreased p16 expression in only
      20% of the tumors but elevated p16 expression in 40% of the tumors when compared
      with the autologous normal controls. Overexpression of p16 was not concomitant
      with loss of the RB protein as is found in several other types of cancers,
      because more than one-half of the tumors with increased p16 expression also had
      high levels of RB protein. On the other hand, the p16 target protein CDK4 was
      overexpressed in at least 60% of the tumors. In the majority of cases, CDK4
      overexpression accompanied elevated p16 and/or RB levels. Our results suggest
      that: (a) alteration of the p16 gene is infrequent in primary soft-tissue
      sarcoma; (b) Cdk4 may act as an oncogene in soft-tissue sarcoma; and (c) elevated
      p16 and RB levels might be the result of compensatory up-regulation of these
      proteins to counteract CDK4 overexpression in these tumors. Our results also
      suggest that it is more informative to examine aberrations in the "p16
      CDK4/cyclin D-RB" pathway than to selectively examine individual components in
      this pathway when investigating genetic changes involved in human malignancy.

PMID- 9563905
TI  - Germ plasm in Caenorhabditis elegans, Drosophila and Xenopus.
AB  - Special cytoplasm, called germ plasm, that is essential for the differentiation
      of germ cells is localized in a particular region of Caenorhabditis elegans,
      Drosophila and Xenopus eggs. The mode of founder cell formation of germline, the
      origin and behavior of the germline granules, and the molecules localized in
      germline cells are compared in these organisms. The common characteristics of the
      organisms are mainly as follows. First, the founder cells of germline are
      established before the initiation of gastrulation. Second, the germline granules
      or their derivatives are always present in germline cells or germ cells
      throughout the life cycle in embryos, larvae, and adults. Lastly, among the
      proteins localized in the germ plasm, only Vasa protein or its homolog is
      detected in the germline cells or germ cells throughout the life cycle. As the
      protein of vasa homolog has been reported to be also localized in the germline
      specific structure or nuage in some of the organisms without the germ plasm, the
      possibility that the mechanism for differentiation of primordial germ cells is
      basically common in all organisms with or without the germ plasm is discussed.

PMID- 9563906
TI  - Difference between dorsal and ventral iris in lens producing potency in normal
      lens regeneration is maintained after dissociation and reaggregation of cells
      from the adult newt, Cynops pyrrhogaster.
AB  - In Wolffian lens regeneration, lentectomized newt eye can produce a new lens from
      the dorsal marginal iris, but the ventral iris has never shown such capabilities.
      To investigate the difference of lens regenerating potency between dorsal and
      ventral iris epithelium at the cellular level, a transplantation system using
      cell reaggregates was developed. Two methods were devised for preparing the
      reaggregates from pigmented iris epithelial cells. One was rotating cells in an
      agar-coated multiplate on a gyratory shaker and the other was incubating cells in
      a microcentrifuge tube after slight centrifugation. Reaggregates made of dorsal
      iris cells that had been completely dissociated into single cells were
      phenotypically transformed into a lens when placed in the pupillary region of the
      lentectomized host eye. None of the ventral reaggregates produced a lens. Even
      dorsal reaggregates could not transdifferentiate into lens when they were placed
      away from the pupil. The produced lenses from the reaggregates were
      morphologically and immunohistochemically identified. To obtain evidence whether
      produced lenses really originated from singly dissociated cells, we labeled
      dissociated cells with a fluorescent dye (PKH26) before reaggregate formation and
      then traced it in the produced lens.

PMID- 9563907
TI  - A method for hormonal induction of sperm release in anurans (eight species) and
      in vitro fertilization in lepidobatrachus species.
AB  - Injections of synthetic human gonadotropin releasing hormone (GnRH) into the
      dorsal pelvic area were used in an attempt to stimulate sperm release in isolated
      males of eight anuran species including Xenopus laevis, Rana pipiens and
      Lepidobatrachus laevis. Sperm were obtained within 1-5 h post injection either by
      mechanical stimulation or by cloacal lavage. Sperm suspensions varied from 8
      microL to 7 mL and the cell densities ranged from 4 x 10(5) to 4 x 10(7)
      sperm/mL. The sperm obtained from seven species using GnRH-induced release were
      viable based on light microscopic observations of motility. In addition, sperm
      preparations fertilized eggs in vitro and produced normal tadpoles in the case of
      L. laevis and L. Ilanensis. This hormonal method of anuran sperm collection will
      provide a convenient non-injurious way to obtain anuran sperm for basic studies
      of reproduction and development.

PMID- 9563908
TI  - Spermatozoon structure and motility in the anuran Lepidobatrachus laevis.
AB  - Synthetic human gonadotropin releasing hormone (GnRH) injections were used for
      induction of spermatozoon release followed by cloacal lavage or mechanical
      stimulation of sperm release in Lepidobatrachus laevis. Light microscopic
      observations of Lepidobatrachus laevis spermatozoa indicated an acrosomal segment
      with a length of 4.1 microm delineated by an indentation, a nuclear region of
      12.6 microm in length and a midpiece of 0.87 microm in length. The tail was 54.9
      microm long by 1.35 microm wide with two lateral axial fibers and a central
      undulating membrane. At the electron microscopic level, the unusual tail had two
      complete axonemes that emanated from the distal centriole. The tail also
      contained two axial fibers 77 nm in diameter medial to the axonemes and was
      connected by an undulating membrane. An unusual accessory cell adherent to the
      head of the spermatozoon was noted in freshly obtained suspensions of
      spermatozoa. Spermatozoa with the accessory cell were motile and a subsequent
      loss of motility was correlated with the shedding of the accessory cell.

PMID- 9563909
TI  - The third egg envelope subunit in fish: cDNA cloning and analysis, and gene
      expression.
AB  - The inner layer of the egg envelope of a teleost fish, the medaka, Oryzias
      latipes, consists of two major subunit groups, ZI-1,2 and ZI-3. On SDS-PAGE, the
      ZI-1,2 group presents three glycoprotein bands that were considered to be
      composed of a common polypeptide moiety derived from their precursor, choriogenin
      H (Chg H). ZI-3 is a single glycoprotein derived from the precursor, choriogenin
      L (Chg L). In the present study, a fraction of a novel subunit protein was found
      in the V8 protease digest of ZI-1.2 that was partially purified from oocyte
      envelopes. This protein fraction was not present in the purified precursor, Chg
      H. By RT-PCR employing the primers based on the amino acid sequence of this
      fraction, a cDNA for the novel subunit was amplified, and a full-length clone of
      the cDNA was obtained by screening a cDNA library constructed from the spawning
      female liver. The clone consisted of 2025 b.p. and contained an open reading
      frame encoding the novel protein of 634 amino acids. This protein included Pro-X
      Y repeat sequences in two-fifths of the whole length from its N-terminus.
      Northern blot analysis revealed that the gene expression for this protein
      occurred in the liver but not in the ovary of spawning female fish. This protein
      is considered as the third major subunit of the inner layer of the egg envelope
      of medaka.

PMID- 9563910
TI  - Neural induction and patterning by fibroblast growth factor, notochord and somite
      tissue in Xenopus.
AB  - Two natural neural inducing sources have been used, the notochord and the somites
      together with the growth factor bFGF, to investigate the anterior/posterior
      patterning of neural tissue in an animal cap explant model in Xenopus laevis.
      Notochord and somite tissue from stages 12.5/13 and 16, respectively, were
      manually isolated, and combined heterochronically with responding animal cap
      ectoderm aged to gastrula stages. Somite recombinants were also constructed with
      animal caps injected with noggin mRNA. The responses of the ectoderm were
      analyzed by reverse transcription polymerase chain reaction (RT-PCR) detection of
      marker gene expression, and in some cases by in situ hybridization. The
      requirement for FGF receptor function was analyzed using the dominant negative
      FGF receptor (XFD). The experiments showed that bFGF is capable of direct neural
      induction in caps aged to stage 10.5. It was also shown that notochords are
      capable of inducing anterior neural tissue in gastrula stage animal cap ectoderm,
      and this induction is sensitive to XFD in the responding tissue. Injection of
      noggin mRNA results in the induction of anterior neural differentiation, and it
      was demonstrated that this induction was insensitive to the expression of XFD in
      the responding tissue. It was also shown that somite tissue recombined with
      gastrula stage animal cap ectoderm, can induce both anterior and posterior
      nervous tissue and can also posteriorize noggin-induced anterior neural tissue
      when combined with noggin-injected animal cap ectoderm. This response is
      partially sensitive to XFD expression. The results shed light on the role of
      competence of animal cap ectoderm and the signals from postgastrulation axial and
      paraxial mesoderm in the patterning of the amphibian nervous system.

PMID- 9563911
TI  - Morphogenic activity of fibroblast growth factor-2 on primary neural precursor
      cells in three-dimensional culture.
AB  - Mouse neural precursor cells (NPC) were dissociated from fetal heads at the 10th
      day of gestation. When clumps of NPC were cultured in collagen gel, they grew and
      reorganized neural tube-like structures in medium containing fetal calf serum at
      10% and supplemented with insulin, transferrin, cholera toxin and selenite.
      However, dissociated NPC died when they were cultured in collagen gel at low
      density in the same medium. Addition of fibroblast growth factor-2 (FGF-2) to
      this culture stimulated growth of NPC and formation of neural tube-like
      structures. The requirement for FGF-2 disappeared in high seeding density
      culture: they grew and formed neural tube-like structures without FGF-2. The
      structures formed in collagen gel were immunohistochemically positive against
      anti-FGF-2 antibody. The results show that the three-dimensional culture system
      provides a useful tool to study the roles of FGF-2 in morphogenesis of the
      central nervous system.

PMID- 9563912
TI  - Sonic hedgehog expression in developing chicken digestive organs is regulated by
      epithelial-mesenchymal interactions.
AB  - Sonic hedgehog (Shh) gene encodes a secreted protein that acts as an important
      mediator of cell-cell interactions. A detailed analysis of Shh expression in the
      digestive organs of the chicken embryo was carried out. Shh expression in the
      endoderm begins at stage 7, when the formation of the foregut commences, and is
      found as narrow bands in the midgut. Shh expression around the anterior
      intestinal portal at stage 15 is restricted to the columnar endoderm lined by the
      thick splanchnic mesoderm, suggesting that the existence of thick splanchnic
      mesoderm might be necessary for Shh expression in the columnar endoderm. After
      the gut is closed, Shh expression is found universally in digestive epithelia,
      including the cecal epithelium. However, its expression ceases in the epithelium
      of the proventricular glands, the ductus choledochus and ductus pancreaticus that
      protrude from the main digestive duct. When the gizzard epithelium differentiated
      into glands under the influence of the proventricular mesenchyme, the glandular
      epithelium lost the ability to express Shh. These findings suggest that Shh
      expression in the epithelium may be regulated by surrounding mesenchyme
      throughout organogenesis of the digestive organs and is closely involved in
      epithelial-mesenchymal interactions in developing digestive organs.

PMID- 9563913
TI  - Regulation of ectodermal differentiation in Xenopus laevis animal caps treated
      with TPA and ammonium chloride.
AB  - Animal caps isolated from Xenopus laevis embryos at the blastula stage were
      treated sequentially with NH4Cl, a known cement gland inducer, and with 12-O
      tetradecanoyl phorbol-13-acetate (TPA), a known neural inducer. The two
      artificial inducers were also used in reverse order to see if they can mimic the
      natural inducers acting during the progressive determination of the ectodermal
      organ. Immunofluorescence and whole-mount in situ hybridization were used to
      study the expression of tubulin, taken to indicate an early step on the pathway
      of cell elongation, and neural cell adhesion molecule (N-CAM) taken to indicate
      an early step in the determination of the nervous system. The expression of XCG
      1, a marker of early specification of the cement gland, was also studied. The
      results showed that the two artificial inducers can mimic the effects of the
      natural inducers in animal cap explants. The TPA behaves like a neural inducer,
      reducing the number and the extension of the cement gland when added to the
      medium in addition to NH4Cl, before or after NH4Cl treatment. In the process of
      cement gland/neural induction, it is possible to redirect the ectoderm already
      specified as cement gland to neural tissue, but it does not seem possible to
      respecify the neural tissue as cement gland. Moreover, the animal caps were also
      cut into dorsal and ventral parts and the two halves were treated separately. The
      results were similar to those obtained with treatment of the entire animal cap,
      suggesting that a dorsal-ventral pattern is not yet established before the
      gastrula stage, and that in normal embryos there are boundaries between the
      effects of different inducers.

PMID- 9563914
TI  - Centrosome-attracting body: a novel structure closely related to unequal
      cleavages in the ascidian embryo.
AB  - The mechanism of unequal cleavage is one of the most intriguing subjects in cell
      biology. Previous studies of unequal cleavage have focused on a limited number of
      organisms such as yeasts, nematodes, sea urchins and annelids. The cleavage
      pattern of the ascidian embryo is invariant. In the ascidian embryo, the
      posterior-most blastomeres divide unequally in three successive cleavages. In the
      present study, it was shown that the ascidian embryo provides another good
      experimental system with which to analyze the mechanism of unequal cleavage. A
      novel structure, designated as CAB (centrosome-attracting body), which was found
      specifically in the unequally cleaving blastomeres was described. In the course
      of unequal cleavages, first, a thick microtubule bundle appeared between CAB and
      one of the centrosomes. Then with the shortening of the microtubule bundle, the
      nucleus with the centrosome was drawn toward CAB, situated at the posterior
      cortex of the blastomere. Finally, a cleavage furrow formed in the middle of the
      asymmetrically located mitotic apparatus and produced two blastomeres of
      different size, generating a smaller cell that inherits CAB. The CAB seemed to
      play an essential role in the unequal cleavages in the ascidian embryo.

PMID- 9563915
TI  - Cloning and expression pattern of Xenopus prx-1 (Xprx-1) during embryonic
      development.
AB  - Homeobox genes are expressed both temporally and spatially during vertebrate
      development, and regulate the tissue-specific expression of other genes. A
      Xenopus paired-related homeobox- 1 (Xprx-1) cDNA was cloned. Xprx-1 had a paired
      related homeodomain, but did not contain a paired-box. The sequence of Xprx-1 had
      a high level of homology with K-2(mouse) and Prx-1 (chicken), thus Xprx-1 is
      assumed to be the Xenopus homolog of these genes. Xprx-1 transcripts were
      maternally restricted, in Xenopus embryos, and a decrease in the late blastula
      stage was followed by an increase in zygotic transcripts after gastrulation. The
      transcripts were localized to the animal hemisphere of the late blastula and were
      concentrated in the branchial arches of the tail-bud stage embryo. In animal cap
      experiments, Activin A dose-dependently induced Xprx-1 gene expression. These
      results suggest that Xprx-1 plays a role in early Xenopus development similar to
      other species.

PMID- 9563916
TI  - Visualization of the initiation and sequential expansion of the metamorphic
      conversion of anuran larval skin into the precursor of adult type.
AB  - A tadpole of bullfrog, Rana catesbeiana, is originally covered with the larval
      skin over its entire body. Drastic changes arise in both the epidermis and the
      subcutaneous connective tissue at an early developmental stage, producing the
      precursor of adult type skin (pre-adult skin). It was found that calcium is a
      useful probe to detect the region where the precursor formation has occurred
      because its deposition in the upper part of subcutaneous collagen bundles
      coincides with the appearance of the pre-adult skin. Whole-mount in situ staining
      of tadpoles with alizarin red S revealed the initiation site of the
      premetamorphic transformation of the larval skin into the adult precursor and its
      ensuing region-dependent expansion. The pre-adult skin first emerged at TK II to
      III (TK, Taylor and Kollros staging) t lateral sides of the body, which led us to
      postulate that 'the center for premetamorphic skin transformation' is formed at
      the specific site in this region. This center moved dorsally and then ventrally,
      then reached to the most proximal region of the tail, yielding a unique
      sequential conversion pattern by around TK V when the conversion was completed in
      the trunk. The present study also visualized the process of the hindlimb skin
      transformation.

PMID- 9563917
TI  - Rapid patterning of Dictyostelium discoideum cells under confined geometry and
      its relation to differentiation.
AB  - The following was recently reported by Bonner et al. (1995): (1) Rapid
      differentiation occurred into two zones in Dictyostelium discoideum cells
      confined in a fine glass capillary. The cells in the anterior zone exposed to the
      air appear similar to prestalk cells, while the posterior zone isolated from the
      air mimics prespore cells. (2) The volumes of the two zones are proportional to
      each other for different sized cell masses, and the proportion is the same as
      that in normal migrating slugs. We investigated the nature of this newly
      discovered rapid differentiation in a slightly modified geometry. Exponentially
      growing cells were harvested, washed to remove external nutrients, and pelleted
      by centrifugation. Subsequently, a small drop of the pelleted (starved) cells was
      placed on a slide glass and then confined in a two-dimensional space between the
      slide glass and a coverslip, with help of spacers whose thickness varied from 25
      to 100 microm. As a result, a dark zone, which looked optically different,
      emerged within several minutes in the periphery of the disc of the confined
      cells, corresponding to the zonation in a capillary as previously reported. When
      the width of the peripheral zone was measured for more than 30 samples of
      different diameters for each thickness of the spacers, the width was found to be
      always about 100 microm, irrespective of the size difference of the cell mass
      placed. This seems to be contradictory to the previous observation made by Bonner
      et al. (1995). We also examined oxygen concentration dependence on the zone
      width. The zone width was found to be independent of the oxygen concentration at
      low concentrations, but increased rapidly at high concentrations. A reaction
      diffusion mechanism for formation of the zone and possible involvement of
      atmospheric oxygen (O2) in the initial steps of cell differentiation and pattern
      formation is discussed.

PMID- 9563918
TI  - Subacute hepatic failure: diagnosis of exclusion?
AB  - Subacute hepatic failure has been a controversial diagnosis ever since it was
      first identified more than 15 years ago. The Working Committee on Subacute
      Hepatic Failure has attempted to redefine this entity in which exclusion of
      preexisting cirrhosis on liver biopsy has been emphasized. Acute viral hepatitis
      in a patient with asymptomatic chronic liver disease (e.g., hepatitis B or C,
      Wilson's disease) can be misdiagnosed as subacute hepatic failure in the absence
      of a liver biopsy. This situation is common in developing countries where the
      prevalence of feco-orally transmitted (hepatitis A [<20 years] and hepatitis E
      [>20 years]) and parenterally transmitted (hepatitis B) viruses is high. To
      obtain and interpret liver biopsy specimens in such a situation is difficult and
      hazardous, and hence rarely performed. Acute viral hepatitis in a patient with
      asymptomatic chronic liver disease should be carefully looked for and excluded,
      especially in developing countries, before a diagnosis of subacute hepatic
      failure is confirmed.

PMID- 9563919
TI  - Hospitalization for gastrointestinal and liver diseases: the effect of
      socioeconomic and medical supply factors.
AB  - A growing body of research has documented significant variation in health care
      use between communities. As the health care system is transformed, providers and
      payers should understand the interaction between a community, its
      sociodemographic characteristics, and its use of health resources. We describe
      the association between a population's demographic, socioeconomic, and medical
      resources and hospital use related to gastrointestinal and liver diseases. We
      used an all-payer hospital discharge database for Michigan from 1986 to 1988. We
      identified all medical and surgical hospital admissions during this period from
      two of the Diagnostic Related Group, Major Diagnostic Categories: No. 6, Diseases
      and Disorders of the Digestive System; and No. 7, Diseases and Disorders of the
      Hepatobiliary System and Pancreas. We analyzed age- and sex-specific use rates.
      Finally, we analyzed the influence of sociodemographic variables from the Area
      Resource File at the county level, on hospital use, using a Poisson regression
      model. We noted a significant association between increased hospitalizations and
      increased age in a community. Hospital beds per capita did not influence
      admission rates overall, although more hospital beds were associated with more
      medical admissions. Overall, the total physician supply was associated with more
      admissions. Finally, the most important socioeconomic variable was education. As
      the level of education of a county increased, hospital admissions decreased
      dramatically. The transformation of the health care delivery system presents
      opportunities and challenges. Understanding the underlying epidemiology of
      disease and how it interacts with a community's socioeconomic and medical
      resources or medical supply characteristics will be necessary to meet the
      community's health needs and to ensure the financial viability of providers. This
      is especially true when payers use a standard payment in a region, such as
      Medicare's managed care payment, without adjustments for the underlying
      population characteristics known to influence use.

PMID- 9563920
TI  - Long-term symptom patterns, endoscopic findings, and gastric histology in
      Helicobacter pylori-infected and -uninfected patients.
AB  - There is a paucity of data on the long-term behavior of dyspepsia, endoscopic
      findings, and gastroduodenal histology in patients with or without Helicobacter
      pylori colonization. We evaluated these parameters during a period of 7 to 19
      years (average, 12.3 years) by baseline and follow-up studies. In 36 patients
      studied, the pattern of gastroduodenal dyspepsia and esophagogastroduodenoscopy
      findings remained essentially unchanged in 67% and 56% respectively. Dyspepsia
      patterns did not correlate significantly with either endoscopic or histologic
      findings, including the severity or location of gastritis in the fundus or
      antrum, or the presence or absence of H. pylori gastritis. Of 36 patients with
      adequate biopsies of the fundus and antrum, H. pylori colonization with gastritis
      was present in 73% but not in 27%. Progression to various degrees of atrophic
      gastritis was noted in 100% with, and in none without, H. pylori gastritis. In
      the fundus, atrophy progressed from 14% to 56%, but intestinal metaplasia did not
      change. In the antrum, atrophy increased from 22% to 64% and intestinal
      metaplasia increased from 17% to 36%. No patient demonstrated dysplasia, but
      severe atrophy was seen in the fundus (6%) and antrum (11%). Only two patients
      (5%) had severe loss of glandular elements and very low pepsinogen I, and thus
      can be considered to have developed advanced gastric atrophy.

PMID- 9563921
TI  - Predictive factors for rebleeding in patients with peptic ulcer bleeding after
      multipolar electrocoagulation: a retrospective analysis.
AB  - The role of endoscopic therapy for peptic ulcer bleeding is well-documented.
      Nevertheless, rebleeding occurs in 10% to 30% of patients, and such patients are
      at high risk for death without early retreatment or definitive surgery. The aim
      of our study was to predict which patients would rebleed within 1 month after
      successful multipolar electrocoagulation of 100 patients with active peptic ulcer
      bleeding (spurting, oozing, or nonbleeding visible vessel). We had achieved
      initial hemostasis in 97 patients and carried out univariate and multivariate
      analyses to predict which patients would rebleed. Rebleeding occurred within 1
      month in 17 (17.5%) patients. we correlated 20 clinical and endoscopic factors
      with rebleeding episodes. With univariate analysis, blood transfusion of 500 ml
      or more at entry (p < 0.0001) and use of cimetidine (p = 0.01) were statistically
      significant for rebleeding. With multivariate analysis, use of omeprazole was an
      independent factor for preventing rebleeding (odds ratio, 7.68; 95% confidence
      interval, 1.642-35.929). We suggest that omeprazole may help to prevent
      rebleeding in patients who have had hemostasis with multipolar
      electrocoagulation.

PMID- 9563922
TI  - Autoimmune (Hashimoto's) thyroiditis associated with Crohn's disease.
AB  - We report the occurrence of autoimmune (Hashimoto's) thyroiditis in three
      patients with Crohn's disease. Previously, thyroid disease has been described
      only in association with ulcerative colitis. We review the pertinent literature
      on thyroid disease in inflammatory bowel disease (IBD) and suggest that this
      association supports the hypothesis that autoimmunity is involved in the
      pathogenesis of IBD. Early diagnosis and treatment of thyroid dysfunction in
      patients with IBD is desirable because thyroid dysfunction worsens the symptoms
      and course of IBD.

PMID- 9563923
TI  - Endotoxemia predicts outcome in acute pancreatitis.
AB  - The incidence of complications of acute pancreatitis is high in patients with
      endotoxemia, and so we determined the endotoxin levels in the blood and
      peritoneal fluid of patients with acute severe pancreatitis to correlate the
      levels with any sequelae. Fourteen patients with acute severe pancreatitis were
      examined with regard to clinical features, biochemical tests, and laparotomy (n =
      9). In all coagulation profiles, blood gas analysis, chest and abdominal x-rays,
      ultrasound, and abdominal computed tomography scan (n = 10) were performed.
      Qualitative estimation of endotoxin levels was done in peripheral blood and
      peritoneal and peripancreatic fluid. Ten (71.42%) of 14 patients had endotoxin in
      the blood, and 9 (64.28%) had it in the peritoneal fluid. Twelve (85.7%) had
      pulmonary involvement, with hypoxia being the most common (85.7%); among them
      endotoxin was found in the blood of 10 (83.32%) and in the peritoneal fluid of 8
      (66.66%) patients. Renal dysfunction was found in 4 (28.57%) patients; endotoxin
      was present in the blood of all 4 patients and in the peritoneal fluid of 3 (75%)
      patients. Cardiovascular abnormality was detected in 8 (57.14%) patients, and
      endotoxin was present in the blood and peritoneal fluid of all patients.
      Metabolic abnormality was present in 8 (57.14%) patients; endotoxin was present
      in the blood of all 8 patients and in the peritoneal fluid of 7 (87.6%) patients.
      Eight (88.88%) of the 9 patients who required surgery had endotoxemia. Three
      (30%) patients with endotoxemia survived, whereas all 4 patients without
      endotoxemia survived. Mean hospital stay was 61.2 days and 46.7 days for
      endotoxin-positive and endotoxin-negative patients, respectively. We conclude
      that the presence of endotoxin in blood and peritoneal fluid correlates with the
      severity, systemic complications, and mortality rates of acute pancreatitis.
      Endotoxin estimation can identify patients at risk in the early stages of acute
      pancreatitis.

PMID- 9563924
TI  - Endoscopic biliary drainage before pancreaticoduodenectomy for periampullary
      malignancies.
AB  - Despite decreased operative mortality, pancreaticoduodenectomy (PD) remains a
      formidable operation with substantial morbidity. We have evaluated the influence
      of preoperative endoscopic biliary drainage (EBD) on morbidity after PD for
      malignant biliary obstruction by retrospectively reviewing the medical records of
      182 patients undergoing PD between April 1985 and August 1996. Of 52 study
      patients with malignant obstructive jaundice, 22 underwent preoperative EBD, and
      30 were not drained. Eighty-three patients were excluded for bilirubin levels
      less than 5 mg/dl, 43 had other biliary drainage, and 4 had jaundice with benign
      pathology. Preoperative, intraoperative, and postoperative factors were compared.
      The two groups were well matched for clinical presentation and operative
      characteristics except for lower preoperative values of liver chemistries in
      patients undergoing EBD. Length of postoperative hospitalization for patients
      undergoing EBD was 13.5 days, compared with 19 days for patients who were not
      drained (p = 0.02). Patients who were not drained tended to have more overall
      complications (p = 0.054). Multivariate analysis revealed time to regular diet (p
      < 0.0001) and no preoperative drainage (p = 0.04) to be independent factors
      significantly increasing the length of hospitalization. Endoscopic biliary
      drainage before PD significantly reduced the length of postoperative
      hospitalization and was associated with less postoperative morbidity. Further
      studies, including cost analysis, are warranted.

PMID- 9563925
TI  - Treatment of chronic hepatitis C with interferon with or without ursodeoxycholic
      acid: a randomized prospective trial.
AB  - The only effective and approved therapy for chronic hepatitis C is interferon
      alpha. Because sustained response rates with interferon alone are disappointingly
      low, multidrug treatment regimens are currently being investigated.
      Ursodeoxycholic acid has been used in other chronic liver diseases and can limit
      hepatocyte injury. To evaluate the potential benefit of ursodeoxycholic acid in
      combination with interferon-alpha for the treatment of chronic hepatitis C, we
      conducted a prospective, double-blinded, randomized, placebo-controlled trial
      comparing the combination therapy of interferon-alpha 2b and ursodeoxycholic acid
      with interferon alone. Thirty-one patients with chronic hepatitis C were
      randomized to receive 3 million units of interferon-alpha 2b subcutaneously three
      times per week and either 13 to 15 mg/kg/day ursodeoxycholic acid or placebo
      orally for 6 months. The 6-month treatment period was followed by 6 months of
      observation. Biochemical normalization at the end of treatment occurred in 5 of
      14 (36%) patients receiving monotherapy versus 8 of 15 (53%) patients (p = 0.34)
      receiving combination therapy. No patient treated with interferon alone had a
      sustained biochemical response 6 months after therapy; however, 3 of 12 patients
      (25%) treated with combination interferon and ursodeoxycholic acid maintained
      biochemical normalization at 6 months after therapy (p = 0.08). No difference in
      liver histology or clearance of hepatitis C viral RNA was noted 6 months after
      treatment. We conclude that combination therapy with ursodeoxycholic acid and
      interferon-alpha 2b was no more effective than interferon monotherapy in inducing
      a biochemical response in previously untreated patients with chronic hepatitis C.
      Ursodeoxycholic acid, however, may be useful in prolonging the biochemical
      response to interferon therapy.

PMID- 9563926
TI  - Expression of interferon receptor genes (IFNAR1 and IFNAR2 mRNA) in the liver may
      predict outcome after interferon therapy in patients with chronic genotype 2a or
      2b hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) genotype 2a or 2b is associated with a favorable outcome
      after interferon therapy. However, 19% to 33% of patients do not respond to
      therapy. We investigated whether interferon receptor gene (IFNAR1 and IFNAR2
      mRNA) expression in the liver before interferon therapy predicts long-term
      response to therapy in patients with genotype 2a or 2b HCV infection. Twenty
      seven patients who subsequently received interferon-alpha therapy underwent liver
      biopsies before interferon therapy. Hepatic IFNAR1 and IFNAR2 mRNA were
      determined using a reverse transcription-polymerase chain reaction assay. Twenty
      (74%) patients responded to interferon therapy, while the remaining seven (26%)
      patients were nonresponders. The expression rates of IFNAR1 and IFNAR2 mRNA in
      the liver were significantly higher in responders than nonresponders (p < 0.01,
      by chi-square test). The presence of either IFNAR1 or IFNAR2 mRNA predicted
      complete response to interferon treatment, with a positive predictive value of
      100%. Multiple logistic regression analysis showed that IFNAR1 and/or IFNAR2 mRNA
      expression was the only significant predictor of the effectiveness of IFN therapy
      (p = 0.0002). We conclude that expression of interferon receptor genes in the
      liver is a useful index for predicting the long-term efficacy of interferon
      therapy in patients with chronic genotype 2a or 2b HCV infection.

PMID- 9563927
TI  - Gastric outlet obstruction caused by microperforation of Helicobacter pylori
      related antral ulcer.
AB  - We report a Helicobacter pylori-related antral gastric ulcer that continued to
      cause symptoms despite H. pylori eradication. The patient had progressive gastric
      outlet obstruction, raising the possibility of a malignancy. On exploratory
      laparotomy, he was found to have a large inflammatory mass surrounding a
      contained microperforation.

PMID- 9563928
TI  - Hepatocellular carcinoma presenting with paraneoplastic neurologic syndrome in a
      hepatitis B surface antigen-positive patient.
AB  - We report a hepatitis B surface antigen-positive patient who presented with
      paraneoplastic peripheral sensorimotor polyneuropathy and cranial nerve
      involvement, 6 months before a diagnosis of hepatocellular carcinoma was made.
      This makes us think that neurologic manifestations in hepatitis B surface antigen
      positive patients warrant investigation to exclude an underlying hepatocellular
      carcinoma.

PMID- 9563929
TI  - Abdominal cocoon in a man: preoperative diagnosis and literature review.
AB  - Sclerosing encapsulating peritonitis, or abdominal cocoon, is a relatively rare
      cause of intestinal obstruction, described mostly in young adolescent girls. It
      is characterized by a thick fibrotic peritoneum that wraps the bowel in a
      concertinalike fashion with some adhesions. Because of its peculiar
      characteristics, this condition presents many difficulties in preoperative
      diagnosis. Recognition of the entity results in proper management and prevents
      unnecessary bowel resection. We report a man with intermittent intestinal
      obstruction and an abdominal cocoon encasing the small bowel that was diagnosed
      preoperatively by radiology. To the best of our knowledge, this represents the
      fourth male patient reported in the medical literature to develop this condition.
      We briefly review the literature and discuss the preoperative diagnosis and
      management of sclerosing encapsulating peritonitis.

PMID- 9563930
TI  - Age-specific diagnostic values of the blood urea nitrogen/creatinine ratio in
      distinguishing upper from lower gastrointestinal bleeding.

PMID- 9563931
TI  - A solitary hematogenous metastasis to the gastric wall from renal cell carcinoma
      four years after radical nephrectomy.

PMID- 9563932
TI  - Nonsteroidal anti-inflammatory drug-induced cecal ulceration diagnosed on barium
      enema.

PMID- 9563933
TI  - Computed tomography in abdominal cocoon.

PMID- 9563934
TI  - Primary pelvic hydatid cyst.

PMID- 9563935
TI  - Unresectable pancreatic adenocarcinoma treated with palladium-103 implant and
      chemoradiation.

PMID- 9563936
TI  - Spontaneous rupture of the amyloid spleen: a report of two cases.

PMID- 9563938
TI  - Can patents deter innovation? The anticommons in biomedical research.
AB  - The "tragedy of the commons" metaphor helps explain why people overuse shared
      resources. However, the recent proliferation of intellectual property rights in
      biomedical research suggests a different tragedy, an "anticommons" in which
      people underuse scarce resources because too many owners can block each other.
      Privatization of biomedical research must be more carefully deployed to sustain
      both upstream research and downstream product development. Otherwise, more
      intellectual property rights may lead paradoxically to fewer useful products for
      improving human health.

PMID- 9563939
TI  - Ordering of ruthenium cluster carbonyls in mesoporous silica 
AB  - The anionic ruthenium cluster carbonylates [Ru6C(CO)16]2- or [H2Ru10(CO)25]2-
      interspersed with bis(triphenylphosphino)iminium counterions (PPN+) are
      incorporated from solution into the pores of MCM-41 mesoporous silica (3
      nanometers in diameter), where they form tightly packed arrays. These arrays were
      shown by high-resolution transmission electron microscopy, Fourier transform
      optical diffraction, and computer simulations to be well ordered both along and
      perpendicular to the axis of the cylindrical pores. In their denuded state
      produced by gentle thermolysis, the cluster carbonylates yield nanoparticles of
      ruthenium that are less well ordered than their assimilated precursors but show
      good activity as hydrogenation catalysts for hexene and cyclooctene. In both
      their as-prepared and denuded states, these encapsulated clusters are likely to
      exhibit interesting electronic and other properties.

PMID- 9563942
TI  - Elucidation of the chain conformation in a glassy polyester, PET, by two
      dimensional NMR 
AB  - The chain conformation of glassy poly(ethylene terephthalate) (PET) was
      characterized by two-dimensional double-quantum nuclear magnetic resonance (NMR).
      In amorphous carbon-13-labeled PET, the statistics of the O-13CH2-13CH2-O torsion
      angle were determined, on the basis of the distinct shapes of the two-dimensional
      NMR patterns of trans and gauche conformations. In crystalline PET, the trans
      content is 100 percent, but in the amorphous PET it is only 14 percent (+/-5
      percent). An average gauche torsion angle of 70 degrees (+/-9 degrees) was
      obtained. Implications for materials properties of polyesters are discussed.

PMID- 9563941
TI  - An analysis of the origins of a cooperative binding energy of dimerization.
AB  - The cooperativity between binding of cell wall precursor analogs (ligands) to and
      antibiotic dimerization of the clinically important vancomycin group antibiotics
      was investigated by nuclear magnetic resonance. When dimerization was weak in the
      absence of a ligand, the increase in the dimerization constant in the presence of
      a ligand derived largely from changes associated with tightening of the dimer
      interface. When dimerization was strong in the absence of a ligand, the increase
      in the dimerization constant in the presence of a ligand derived largely from
      changes associated with tightening of the ligand-antibiotic interface. These
      results illustrate how, when a protein has a loose structure, the binding energy
      of another molecule to the protein can derive in part from changes occurring
      within the protein.

PMID- 9563940
TI  - A trivalent system from vancomycin.D-ala-D-Ala with higher affinity than
      avidin.biotin.
AB  - Tris(vancomycin carboxamide) binds a trivalent ligand derived from D-Ala-D-Ala
      with very high affinity: dissociation constant (Kd) approximately 4 x 10(-17) +/-
      1 x 10(-17) M. High-affinity trivalent binding and monovalent binding are
      fundamentally different. In trivalent (and more generally, polyvalent) binding,
      dissociation occurs in stages, and its rate can be accelerated by monovalent
      ligand at sufficiently high concentrations. In monovalent binding, dissociation
      is determined solely by the rate constant for dissociation and cannot be
      accelerated by added monomer. Calorimetric measurements for the trivalent system
      indicate an approximately additive gain in enthalpy relative to the corresponding
      monomers. This system is one of the most stable organic receptor-ligand pairs
      involving small molecules that is known. It illustrates the practicality of
      designing very high-affinity systems based on polyvalency.

PMID- 9563943
TI  - Effect of substrate strain on adsorption 
AB  - Direct evidence for the effect of local strain at a surface on the bonding
      strength for adsorbates is presented. Scanning tunneling microscopy revealed that
      adsorbed oxygen atoms on Ru(0001) surfaces are located preferentially on top of
      nanometer-size protrusions above subsurface argon bubbles, where tensile strain
      prevails, and are depleted around their rim in regions of compression, relative
      to the flat surface. Such effects can be considered as the reverse of adsorbate
      induced strain, and their direct local demonstration can be used to test
      theoretical predictions.

PMID- 9563944
TI  - Micromechanical "Trampoline" magnetometers for use in large pulsed magnetic
      fields 
AB  - A silicon micromechanical magnetometer was constructed and successfully used in
      60-tesla pulsed magnetic fields of less than 100-millisecond duration. The device
      is small, inexpensive to fabricate, and easy to use. It features a fast
      mechanical response (up to 50,000 hertz) and extremely high sensitivity yet is
      relatively robust against electrical and mechanical noise. Quantum oscillations
      in the magnetization of a 1-microgram sample of an organic superconductor, kappa
      [bis(ethylenedithio)tetrathiafulvalene]2Cu(NCS)2, have been observed with this
      device.

PMID- 9563946
TI  - Deep-Sea coral evidence for rapid change in ventilation of the deep north
      atlantic 15,400 years Ago 
AB  - Coupled radiocarbon and thorium-230 dates from benthic coral species reveal that
      the ventilation rate of the North Atlantic upper deep water varied greatly during
      the last deglaciation. Radiocarbon ages in several corals of the same age, 15.41
      +/- 0.17 thousand years, and nearly the same depth, 1800 meters, in the western
      North Atlantic Ocean increased by as much as 670 years during the 30- to 160-year
      life spans of the samples. Cadmium/calcium ratios in one coral imply that the
      nutrient content of these deep waters also increased. Our data show that the deep
      ocean changed on decadal-centennial time scales during rapid changes in the
      surface ocean and the atmosphere.

PMID- 9563945
TI  - Reductive dechlorination of DDE to DDMU in marine sediment microcosms.
AB  - DDT is reductively dechlorinated to DDD and dehydrochlorinated to DDE; it has
      been thought that DDE is not degraded further in the environment. Laboratory
      experiments with DDE-containing marine sediments showed that DDE is dechlorinated
      to DDMU in both methanogenic and sulfidogenic microcosms and that DDD is
      dehydrochlorinated to DDMU three orders of magnitude more slowly. Thus, DDD does
      not appear to be an important precursor of the DDMU found in these sediments.
      These results imply that remediation decisions and risk assessments based on the
      recalcitrance of DDE in marine and estuarine sediments should be reevaluated.

PMID- 9563947
TI  - Local orbital forcing of antarctic climate change during the last interglacial 
AB  - During the last interglacial, Antarctic climate changed before that of the
      Northern Hemisphere. Large local changes in precession forcing could have
      produced this pattern if there were a rectified response in sea ice cover.
      Results from a coupled sea ice-ocean general circulation model supported this
      hypothesis when it was tested for three intervals around the last interglacial.
      Such a mechanism may play an important role in contributing to phase offsets
      between Northern and Southern Hemisphere climate change for other time intervals.

PMID- 9563948
TI  - Cope's rule and the dynamics of body mass evolution in North American fossil
      mammals.
AB  - Body mass estimates for 1534 North American fossil mammal species show that new
      species are on average 9.1% larger than older species in the same genera. This
      within-lineage effect is not a sampling bias. It persists throughout the
      Cenozoic, accounting for the gradual overall increase in average mass (Cope's
      rule). The effect is stronger for larger mammals, being near zero for small
      mammals. This variation partially explains the unwavering lower size limit and
      the gradually expanding mid-sized gap, but not the sudden large increase in the
      upper size limit, at the Cretaceous-Tertiary boundary.

PMID- 9563949
TI  - Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor.
AB  - Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major
      cause of death in animals infected with anthrax. One component of this toxin,
      lethal factor (LF), is suspected to be a metalloprotease, but no physiological
      substrates have been identified. Here it is shown that LF is a protease that
      cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2
      (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the
      MAPK signal transduction pathway. The identification of a cleavage site for LF
      may facilitate the development of LF inhibitors.

PMID- 9563950
TI  - Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is caused by a CTG expansion in the 3' untranslated
      region of the DM gene. One model of DM pathogenesis suggests that RNAs from the
      expanded allele create a gain-of-function mutation by the inappropriate binding
      of proteins to the CUG repeats. Data presented here indicate that the conserved
      heterogeneous nuclear ribonucleoprotein, CUG-binding protein (CUG-BP), may
      mediate the trans-dominant effect of the RNA. CUG-BP was found to bind to the
      human cardiac troponin T (cTNT) pre-messenger RNA and regulate its alternative
      splicing. Splicing of cTNT was disrupted in DM striated muscle and in normal
      cells expressing transcripts that contain CUG repeats. Altered expression of
      genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM
      pathogenesis.

PMID- 9563951
TI  - Yeast Ku as a regulator of chromosomal DNA end structure.
AB  - During telomere replication in yeast, chromosome ends acquire an S-phase-specific
      overhang of the guanosine-rich strand. Here it is shown that in cells lacking Ku,
      a heterodimeric protein involved in nonhomologous DNA end joining, these
      overhangs are present throughout the cell cycle. In vivo cross-linking
      experiments demonstrated that Ku is bound to telomeric DNA. These results show
      that Ku plays a direct role in establishing a normal DNA end structure on yeast
      chromosomes, conceivably by functioning as a terminus-binding factor. Because Ku
      mediated DNA end joining involving telomeres would result in chromosome
      instability, our data also suggest that Ku has a distinct function when bound to
      telomeres.

PMID- 9563952
TI  - Modulation of diversity by grazing and mowing in native tallgrass prairie 
AB  - Species diversity has declined in ecosystems worldwide as a result of habitat
      fragmentation, eutrophication, and land-use change. If such decline is to be
      halted ecological mechanisms that restore or maintain biodiversity are needed.
      Two long-term field experiments were performed in native grassland to assess the
      effects of fire, nitrogen addition, and grazing or mowing on plant species
      diversity. In one experiment, richness declined on burned and fertilized
      treatments, whereas mowing maintained diversity under these conditions. In the
      second experiment, loss of species diversity due to frequent burning was reversed
      by bison, a keystone herbivore in North American grasslands. Thus, mowing or the
      reestablishment of grazing in anthropogenically stressed grasslands enhanced
      biodiversity.

PMID- 9563953
TI  - Anterior cingulate cortex, error detection, and the online monitoring of
      performance.
AB  - An unresolved question in neuroscience and psychology is how the brain monitors
      performance to regulate behavior. It has been proposed that the anterior
      cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to
      performance monitoring by detecting errors. In this study, event-related
      functional magnetic resonance imaging was used to examine ACC function. Results
      confirm that this region shows activity during erroneous responses. However,
      activity was also observed in the same region during correct responses under
      conditions of increased response competition. This suggests that the ACC detects
      conditions under which errors are likely to occur rather than errors themselves.

PMID- 9563954
TI  - Actin mutations in dilated cardiomyopathy, a heritable form of heart failure.
AB  - To test the hypothesis that actin dysfunction leads to heart failure, patients
      with hereditary idiopathic dilated cardiomyopathy (IDC) were examined for
      mutations in the cardiac actin gene (ACTC). Missense mutations in ACTC that
      cosegregate with IDC were identified in two unrelated families. Both mutations
      affect universally conserved amino acids in domains of actin that attach to Z
      bands and intercalated discs. Coupled with previous data showing that dystrophin
      mutations also cause dilated cardiomyopathy, these results raise the possibility
      that defective transmission of force in cardiac myocytes is a mechanism
      underlying heart failure.

PMID- 9563955
TI  - Ribonuclease P protein structure: evolutionary origins in the translational
      apparatus.
AB  - The crystal structure of Bacillus subtilis ribonuclease P protein is reported at
      2.6 angstroms resolution. This protein binds to ribonuclease P RNA to form a
      ribonucleoprotein holoenzyme with optimal catalytic activity. Mutagenesis and
      biochemical data indicate that an unusual left-handed betaalphabeta crossover
      connection and a large central cleft in the protein form conserved RNA binding
      sites; a metal binding loop may comprise a third RNA binding site. The unusual
      topology is partly shared with ribosomal protein S5 and the ribosomal translocase
      elongation factor G, which suggests evolution from a common RNA binding ancestor
      in the primordial translational apparatus.

PMID- 9563956
TI  - Measuring outcome after liver transplantation: a critical review.
AB  - As the number of liver transplantations performed around the world and the
      survival rates increase, attention is turning to the broad impact this procedure
      has on patients' quality of life (QOL), including their physical and psychosocial
      functioning and their perceived sense of well-being. There exists a small body of
      literature that examines the global effects of liver transplantation on QOL. The
      purpose of this article is to discuss the general framework used to assess QOL
      and to critically review the studies that have broadly examined QOL outcomes
      after liver transplantation. The reviewed studies used measures that led to broad
      assessment of the various domains of QOL. Although the instruments used to
      measure QOL in these studies are largely validated, there is significant
      heterogeneity in this literature in terms of the instruments used, leading to
      difficulties in making generalizable conclusions among the studies. Although
      limited by internal validity problems, the available data suggest improvement in
      QOL by liver transplantation. Additionally, a large recent study that used the
      Liver Transplant Database Quality of Life Questionnaire also reported a subset of
      patients in whom QOL seemed to worsen after liver transplantation. Knowledge of
      the factors related to QOL outcome after liver transplantation is important
      because it might allow development of new interventions that may have an impact
      on future allocation decisions.

PMID- 9563957
TI  - Incidence and severity of acute allograft rejection in liver transplant
      recipients treated with alfa interferon.
AB  - Interferon alfa-2b (IFN-alpha) therapy has been shown to be effective in the
      treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who
      did not undergo transplantation. However, in allograft recipients, treatment with
      IFN-alpha often leads to allograft rejection. The aim of the present study was to
      determine if IFN-alpha therapy increases the incidence or severity of acute
      rejection in human liver allograft recipients. One hundred five orthotopic liver
      transplant (OLT) recipients with HBV (n = 32), HCV (n = 58), or Non A Non B Non C
      (n = 15) viral infections were treated with a 6-month course of IFN-alpha, 5
      million U subcutaneously three times a week, which began 2 to 97 months after
      transplantation. The mean hepatitis activity index (HAI) at the beginning of the
      therapy was 10.1 +/- 3.0. The baseline immunosuppression was achieved by
      tacrolimus in 77 patients and by cyclosporine A (CyA) in 28 patients.
      Contemporaneous controls consisted of 132 OLT patients (100 who received
      tacrolimus and 32 who received CyA) who did not receive IFN-alpha. A
      retrospective analysis was performed on this group of patients. The incidence of
      rejection and the baseline immunosuppression were compared. All biopsies were
      reviewed without knowledge of clinical data and scored for HAI and for rejection
      activity index (RAI). The biochemical response to IFN-alpha was also examined.
      The mean baseline maintenance dose of prednisone was greater by 2 mg daily in
      patients who received IFN-alpha with tacrolimus compared with control patients
      who did not receive IFN-alpha with tacrolimus (IFN-alpha 5. 3 +/- 5.2 mg daily v
      controls 3.3 +/- 4.9 mg daily; P </= .05). Similarly, the mean maintenance dose
      of prednisone was greater by 2.5 mg daily in patients who received IFN-alpha
      compared with controls who received CyA-based immunosuppression (IFN-alpha 9.8 +/
      3.1 mg daily v controls 7.3 +/- 3.3 mg daily; P = .01). Acute rejection episodes
      were detected in 10.5% (n = 11) of IFN-alpha-treated patients compared with 8.8%
      of controls for the similar time period from OLT and period of exposure to risk
      of rejection. Mean RAI was 2.0 +/- 2.4 for the IFN-alpha-treated group and 2.1 +/
      1.7 for controls. Rejection episodes with IFN-alpha treatment were mild and
      responded to steroid therapy. In OLT recipients, the risk of acute rejection was
      not increased by the introduction of IFN-alpha. However, in this study, patients
      were exposed to greater levels of immunosuppression.

PMID- 9563958
TI  - Inflammatory process complicating giant hemangioma of the liver: report of three
      cases.
AB  - Three cases of giant hemangioma of the liver associated with clinical and
      laboratory signs of inflammatory process, including low-grade fever, weight loss,
      abdominal pain, accelerated erythrocyte sedimentation rate, anemia,
      thrombocytosis, and increased fibrinogen level with normal white blood cell count
      are described. One patient presented with slight cholestatic jaundice because of
      tumor-related bile duct compression, but the other two patients had normal liver
      function tests, except for a slight increase in gammaglutamyl transferase.
      Clinical and laboratory abnormalities disappeared after surgical excision.
      Inflammatory manifestations have rarely been reported during giant liver
      hemangioma. Intratumoral inflammation necrosis or bleeding could explain the
      symptoms but histological signs of inflammation were not detected in two of three
      surgical specimens. The release of immune mediators by liver endothelial cells
      lining the hemangioma is an alternative explanation. The incidence of
      inflammatory process complicating giant hemangioma is probably underestimated
      because our three cases were observed within a span of only 3 years.

PMID- 9563959
TI  - Allograft rejection after liver transplantation for autoimmune liver diseases.
AB  - Autoimmune liver diseases (AILD) may progress to liver failure, requiring liver
      transplantation as definitive therapy, and these immune-mediated disorders may
      predispose the patient to more frequent graft rejection. The objective of this
      study was to determine the effect of preexisting AILD on the incidence of
      allograft rejection after liver transplantation. Sixty-three patients who
      underwent liver transplantation between March 1988 and December 1994 for AILDs
      that included autoimmune hepatitis (AIH; n = 33) and primary biliary cirrhosis
      (PBC; n = 30) were retrospectively compared with 47 patients who underwent liver
      transplantation for alcoholic cirrhosis during the same time period. There was a
      lower incidence of acute allograft rejection in patients with AILD who received
      tacrolimus-based compared with cyclosporine-based immunosuppression (50% v 85.5%;
      P = .02). However, patients with AILDs overall had a higher incidence of acute
      rejection than patients with alcoholic cirrhosis (81% v 46.8%; P < .001),
      regardless of the type of immunosuppression. In addition, steroid-resistant
      rejection occurred more frequently in patients with AILDs than in patients with
      alcoholic cirrhosis (38.1% v 12.8%; P = .003). There was also a trend toward a
      higher incidence of chronic rejection in patients with AILDs compared with
      patients with alcoholic cirrhosis (11.1% v 2.1%), but this difference did not
      reach statistical significance. Patient and graft survivals at 1 and 3 years were
      similar between patients with AILDs and alcoholic liver disease. Compared with
      alcoholic cirrhosis, preexisting AILDs are associated with a higher incidence of
      acute allograft rejection and a trend toward more frequent chronic rejection.

PMID- 9563960
TI  - Health-related quality of life after liver transplantation.
AB  - To gather information regarding how to best assist liver transplant recipients in
      improving their self-care capacity and well-being, we investigated their total
      health situation. A retrospective, cross-sectional survey with up to a 10-year
      follow-up concerning experienced health and quality of life after liver
      transplantation (LTX) was conducted. The aim of this study was to provide
      descriptive data on the experienced health and health-related quality of life
      (HRQOL) after LTX and to evaluate whether the pretransplantation medical
      conditions affected these parameters. All patients who had undergone LTX, were
      alive at the time of the study, and had a follow-up of more than 6 months (n =
      134) were asked to complete three self-administered questionnaires. The response
      rate was 95% (n = 120). There was no correlation between pretransplantation Child
      Pugh score and HRQOL after LTX. Liver transplant recipients were more limited in
      their physical health than healthy subjects but were equal in social functioning
      and mental health. Twenty-six percent suffered from severe bodily pain. A
      significant difference was reported in all health areas, with the exception of
      vitality and social functioning, between employed and unemployed transplant
      recipients. Liver transplant recipients suffered from limited physical
      functioning many years after transplantation. Their social functioning and mental
      health were not negatively affected. This study emphasizes that bodily pain and
      difficulties in performing regular activities because of physical illness are
      problems frequently experienced by liver transplant recipients.

PMID- 9563961
TI  - Percutaneous mesenteric venous thrombectomy and thrombolysis: successful
      treatment followed by liver transplantation.
AB  - Mesenteric vein thrombosis (MVT) is a rare cause of intestinal ischemia. Because
      of its nonspecific symptoms, diagnosis is often delayed. We describe a patient
      with liver cirrhosis who developed acute MVT while waiting for liver
      transplantation. Surgical intervention carried a high risk because of her
      underlying cirrhosis. Mesenteric venous thrombectomy and thrombolysis were
      performed with an AngioJet (Possis Medical, Minneapolis, MN) thrombectomy device
      and streptokinase infusion through transjugular route. The patient subsequently
      received an orthotopic liver transplant. We also present a review of the
      literature about the occurrence and treatment options for MVT.

PMID- 9563962
TI  - Division of the left hemiliver in man--segments, sectors, or sections.
AB  - A major obstacle to coherent terminology for liver anatomy and resections has
      been that American and French anatomists have divided the left side of the liver
      through different planes. Couinaud divided the left hemiliver into "sectors" by a
      plane through the left hepatic vein. Healey and Schroy divided it into "segments"
      through the umbilical fissure. One anatomic justification for Couinaud's system
      of sectors is that the transverse portion of the left portal vein was said to
      terminate by dividing into the umbilical portion of the left portal vein and the
      vein to segment II. However, corrosion cast studies fail to consider the position
      of the ligamentum venosum, the structure defining the end of the transverse
      portion of the left portal vein. Therefore, it is uncertain whether the branch to
      segment II is a terminal branch of the transverse portion of the left portal vein
      or a branch of the first part of the umbilical portion. Ten cadaver livers were
      dissected to determine the position of the branch to segment II in relation to
      the ligamentum venosum. In all, the branch to segment II came off downstream to
      the ligamentum venosum, showing that it is a branch of the umbilical portion of
      the left portal vein. This study does not support the "sectoral" system of
      Couinaud on the left side of the liver. Division of the left side of the liver
      through the umbilical fissure as proposed by Healey is anatomically logical and
      fits well with common surgical resections.

PMID- 9563963
TI  - Use of infrarenal conduits for arterial revascularization in orthotopic liver
      transplantation.
AB  - Arterial conduits that use donor iliac arteries represent a reliable technique
      for graft revascularization in orthotopic liver transplantation. We reviewed 757
      consecutive liver transplantations performed between 1989 and 1995 for acute or
      chronic liver disease in adults and children. Of these, 218 patients received
      arterial conduits that used donor iliac arteries. The incidence of hepatic artery
      thrombosis (HAT) for conduits was 4.1% (9 of 218 patients) compared with 4% (22
      of 539 patients) for direct arterial anastomosis. Patients in the arterial
      conduit group included 66% (99 of 159) of the children younger than 5 years of
      age, 75% (67 of 89) of all patients who underwent retransplantation, and, in
      particular, 25 patients regrafted for HAT. Arterial conduits provide an effective
      and reliable method of revascularization in patients at higher risk of arterial
      thrombosis. The actuarial 3-year patency rate for conduits is 95% and the
      incidence of HAT is similar to that in standard arterial anastomoses.

PMID- 9563964
TI  - Domino liver transplantation for familial amyloid polyneuropathy.
AB  - Familial amyloid polyneuropathy is an autosomal dominant disorder in which the
      liver produces a variant prealbumin that is deposited along nerves, leading to a
      progressive and fatal polyneuropathy that begins in the third decade of life.
      Liver transplantation has been the only successful treatment to date. Apart from
      the production of the variant protein, there are no other abnormalities in these
      amyloid livers. We describe two cases in which, at the time of transplantation,
      the amyloid livers were subsequently used for transplantation in another patient,
      and we discuss the implications.

PMID- 9563965
TI  - Cavoatrial shunt: a graft salvage procedure for suprahepatic caval anastomosis
      obstruction after liver transplantation.
AB  - A liver transplant recipient developed the Budd-Chiari syndrome because of an
      obstruction of the suprahepatic inferior vena cava anastomosis. Percutaneous
      balloon dilatation angioplasty was not feasible. On exploration, dense
      retrohepatic fibrotic reaction was observed. The patient underwent successful
      retrohepatic cavoatrial shunt placement by means of a 16-mm, ring-enforced
      polytetrafluoroethylene graft. We conclude that this shunt should be considered
      an additional graft salvage procedure for this complication.

PMID- 9563966
TI  - Vessel loop-guided technique for parenchymal transection in living donor or in
      situ split-liver procurement.

PMID- 9563967
TI  - Withdrawal of immunosuppression in liver allograft recipients.

PMID- 9563968
TI  - Expanded donor pool 
AB  - No Abstract Copyright

PMID- 9563969
TI  - The criteria for liver transplantation vary widely throughout the United States.

PMID- 9563970
TI  - Meetings 
AB  - No Abstract Copyright

PMID- 9563973
TI  - Isolation and structural analysis of microsomal membrane proteins.
AB  - Investigation of the endoplasmic reticulum requires a methodological background
      in the solubilization, purification, and structural analysis of membrane
      proteins. The experience of one laboratory with microsomal proteins over 30 years
      is summarized in this review. We focus on the isolation and structure of the
      major proteins of rabbit liver microsomes. The special pitfalls encountered with
      fragile protein complexes, hydrophobic peptides, and post-translational
      modifications are emphasized.

PMID- 9563974
TI  - Aminoalkylaziridines as substrates and inhibitors of lysyl oxidase: specific
      inactivation of the enzyme by N-(5-aminopentyl)aziridine.
AB  - The reaction of lysyl oxidase was assessed with members of a series of
      aminoalkylaziridines in which the primary amino group and the aziridinyl nitrogen
      were separated by 3-7 methylene carbons. Among these, N-(5-aminopentyl)aziridine
      proved to be the poorest substrate by far and to inhibit the enzyme activity.
      Aminoalkylaziridines with chain lengths shorter or longer than five carbons did
      not inhibit the enzyme. The resulting inhibition was competitive with productive
      substrates and became irreversible with time, following pseudo first order
      kinetics with a KI of 0.22 mM. N-(5-aminopentyl)aziridine appears to act as a
      bifunctional affinity label covalently interacting with the active site of this
      enzyme.

PMID- 9563975
TI  - A study of the effect of renal pelvic and ureteric distention on the anorectal
      function with identification of the "reno-anal reflex".
AB  - Renal or ureteral diseases are often associated with gastrointestinal symptoms.
      In this communication, we studied the effect of renal pelvic or ureteric
      distension on the anorectal function in 12 healthy volunteers. A 3F balloon
      tipped catheter was introduced into the renal pelvis. The balloon was filled with
      saline in increments of 2 ml up to 12 ml and the pressure response of the rectum
      and anal canal was recorded. Balloon filling was performed twice: rapidly (1
      ml/sec) and slowly (1 ml/min). The test was repeated in the ureter with balloon
      fillings in increments of 0.25 ml up to 1 ml. The electromyographic (EMG)
      response of the external anal sphincter to distension of the renal pelvis or
      ureter was evaluated. The pressure response of the rectum, anal canal and
      external anal sphincter to distension of the anesthetised renal pelvis or ureter
      was then determined. The test was repeated after external anal sphincter
      anaesthetisation. Rapid renal pelvic or ureteric distension increased the anal
      canal pressure (p < 0.05) but did not change the rectal pressure (p > 0.05). With
      10 and 12 ml rapid renal pelvis distension and with 0.75 and 1 ml rapid ureteric
      distension, the EMG activity of the external anal sphincter increased and was
      accompanied with loin and anal pain. Slow renal pelvic or ureteric distension
      caused no significant change in the anal or rectal pressures (p > 0.05) or in the
      EMG activity of the external anal sphincter and no anal pain was perceived.
      Distension of the anesthetised renal pelvis or ureter effected no changes in anal
      or rectal pressures (p > 0.05). The anesthetised external anal sphincter as well
      as the anal or rectal pressure did not respond to renal pelvis or ureteric
      distension. In conclusion, rapid renal pelvic or ureteric distension stimulates
      the mechanoreceptors in the renal pelvis or ureteric wall leading to reflex
      external anal sphincter contraction. This leads to elevation of the anal canal
      pressure. The findings suggest the possible involvement of a "reno-anal reflex"
      which is evoked on rapid renal pelvis or ureteric distension. Slow distension
      does not seem to trigger such a reflex.

PMID- 9563976
TI  - The health effects of oilseed rape: myth or reality?. No clear evidence that it
      has adverse effects on health.

PMID- 9563978
TI  - Models of cardiac rehabilitation. Multidisciplinary rehabilitation is worthwhile,
      but how is it best delivered?

PMID- 9563977
TI  - Endothelial cell activation. A central pathophysiological process.

PMID- 9563979
TI  - Lithium. Still effective despite its detractors.

PMID- 9563980
TI  - Maintaining privacy and the health of the public. Should not be seen as in
      opposition.

PMID- 9563981
TI  - ISIS-2: 10 year survival among patients with suspected acute myocardial
      infarction in randomised comparison of intravenous streptokinase, oral aspirin,
      both, or neither. The ISIS-2 (Second International Study of Infarct Survival)
      Collaborative Group.
AB  - OBJECTIVE: To assess effects of intravenous streptokinase, one month of oral
      aspirin, or both, on long term survival after suspected acute myocardial
      infarction. DESIGN: Randomised, "2 x 2 factorial," placebo controlled trial.
      SETTING: 417 hospitals in 16 countries. SUBJECTS: 17 187 patients with suspected
      acute myocardial infarction randomised between March 1985 and December 1987.
      Follow up of vital status complete to at least 1 January 1990 for 95% of all
      patients and to mid-1997 for the 6213 patients in United Kingdom. INTERVENTIONS:
      Intravenous streptokinase (1.5 MU in 1 hour) and oral aspirin (162 mg daily for 1
      month) versus matching placebos. MAIN OUTCOME MEASURES: Mortality from all causes
      during up to 10 years' follow up, with subgroup analyses based on 4 year follow
      up. RESULTS: After randomisation, 1841 deaths were recorded in days 0-35, 991
      from day 36 to end of year 1, 1478 in years 2-4, and 1230 in years 5-10.
      Allocation to streptokinase was associated with 29 (95% confidence interval 20 to
      38) fewer deaths per 1000 patients during days 0-35. This early benefit persisted
      (death rate ratio 0.98 (0.92 to 1.04) for additional deaths between day 36 and
      end of year 10), so that there were 28 (14 to 42) and 23 (2 to 44) fewer deaths
      per 1000 patients treated with streptokinase after 4 years and 10 years
      respectively. There was no evidence that absolute survival benefit increased with
      prolonged follow up among any category of patient, including those presenting
      early after symptoms started or with anterior ST elevation. Nor did the early
      benefits seem to be lost in any category (including those aged over 70).
      Allocation to one month of aspirin was associated with 26 (16 to 35) fewer deaths
      per 1000 during first 35 days, with little further benefit or loss during
      subsequent years (death rate ratio 0.99 (0.93 to 1.06) between day 36 and end of
      year 10). The early benefit obtained with combination of streptokinase and one
      month of aspirin also seemed to persist long term. CONCLUSIONS: The early
      survival advantages produced by fibrinolytic therapy and one month of aspirin
      started in acute myocardial infarction seem to be maintained for at least 10
      years.

PMID- 9563982
TI  - Fetal and maternal contributions to risk of pre-eclampsia: population based
      study.
AB  - OBJECTIVE: To use familial patterns of recurrence of pre-eclampsia to investigate
      whether paternal genes expressed in the fetus contribute to the mother's risk of
      pre-eclampsia and whether mother's susceptibility to pre-eclampsia is related to
      maternal inheritance by mitochondrial DNA. DESIGN: Linked data on pregnancies of
      different women who had children with the same father, and subsequently linked
      data on pregnancies of half sisters who either had same mother and different
      fathers or had same father and different mothers. SETTING: Population based data
      from the Medical Birth Registry of Norway covering all births since 1967 (about
      1.7 million) and the Norwegian Central Population Register. MAIN OUTCOME
      MEASURES: Relative risk of pre-eclampsia after a previous pre-eclamptic pregnancy
      in the family. Relative risks approximated by odds ratios. RESULTS: If a woman
      becomes pregnant by a man who has already fathered a pre-eclamptic pregnancy in a
      different woman her risk of developing pre-eclampsia is 1.8 (95% confidence
      interval 1.2 to 2.6). If the woman has a half sister who had pre-eclampsia and
      with whom she shares the same mother but different fathers the risk of pre
      eclampsia is 1.6 (0.9 to 2.6). If the two sisters have the same father but
      different mothers the risk is 1.8 (1.01 to 2.9). CONCLUSIONS: Both the mother and
      the fetus contribute to the risk of pre-eclampsia, the contribution of the fetus
      being affected by paternal genes. Mitochondrial genes, which are transmitted by
      mothers, do not seem to contribute to the risk.

PMID- 9563983
TI  - Randomised trial of impact of model of integrated care and case management for
      older people living in the community.
AB  - OBJECTIVE: To evaluate the impact of a programme of integrated social and medical
      care among frail elderly people living in the community. DESIGN: Randomised study
      with 1 year follow up. SETTING: Town in northern Italy (Rovereto). SUBJECTS: 200
      older people already receiving conventional community care services.
      INTERVENTION: Random allocation to an intervention group receiving integrated
      social and medical care and case management or to a control group receiving
      conventional care. MAIN OUTCOME MEASURES: Admission to an institution, use and
      costs of health services, variations in functional status. RESULTS: Survival
      analysis showed that admission to hospital or nursing home in the intervention
      group occurred later and was less common than in controls (hazard ratio 0.69; 95%
      confidence interval 0.53 to 0.91). Health services were used to the same extent,
      but control subjects received more frequent home visits by general practitioners.
      In the intervention group the estimated financial savings were in the order of
      1125 ($1800) per year of follow up. The intervention group had improved physical
      function (activities of daily living score improved by 5.1% v 13.0% loss in
      controls; P<0.001). Decline of cognitive status (measured by the short portable
      mental status questionnaire) was also reduced (3.8% v 9.4%; P<0.05). CONCLUSION:
      Integrated social and medical care with case management programmes may provide a
      cost effective approach to reduce admission to institutions and functional
      decline in older people living in the community.

PMID- 9563984
TI  - Inappropriate use of sumatriptan: population based register and interview study.

PMID- 9563986
TI  - Adherence to cardiac rehabilitation guidelines: a survey of rehabilitation
      programmes in the United Kingdom.

PMID- 9563985
TI  - Is cardiothoracic ratio in healthy middle aged men an independent predictor of
      coronary heart disease mortality? Whitehall study 25 year follow up.

PMID- 9563988
TI  - Alternative definitions 

PMID- 9563987
TI  - Why I went to oxford, not cambridge 

PMID- 9563989
TI  - Ether drinking in east prussia 

PMID- 9563990
TI  - Outcome of low back pain in general practice: a prospective study.
AB  - OBJECTIVES: To investigate the claim that 90% of episodes of low back pain that
      present to general practice have resolved within one month. DESIGN: Prospective
      study of all adults consulting in general practice because of low back pain over
      12 months with follow up at 1 week, 3 months, and 12 months after consultation.
      SETTING: Two general practices in south Manchester. 490 subjects (203 men, 287
      women) aged 18-75 years. MAIN OUTCOME MEASURES: Proportion of patients who have
      ceased to consult with low back pain after 3 months; proportion of patients who
      are free of pain and back related disability at 3 and 12 months. RESULTS: Annual
      cumulative consultation rate among adults in the practices was 6.4%. Of the 463
      patients who consulted with a new episode of low back pain, 275 (59%) had only a
      single consultation, and 150 (32%) had repeat consultations confined to the 3
      months after initial consultation. However, of those interviewed at 3 and 12
      months follow up, only 39/188 (21%) and 42/170 (25%) respectively had completely
      recovered in terms of pain and disability. CONCLUSIONS: The results are
      consistent with the interpretation that 90% of patients with low back pain in
      primary care will have stopped consulting with symptoms within three months.
      However most will still be experiencing low back pain and related disability one
      year after consultation.

PMID- 9563991
TI  - Molecular assessment of cancer.

PMID- 9563992
TI  - Two cases of retention of wooden foreign bodies in orbit of eye.

PMID- 9563993
TI  - Venom allergy.

PMID- 9563994
TI  - Do I say anything? 

PMID- 9563995
TI  - North of England evidence based development project: guideline for angiotensin
      converting enzyme inhibitors in primary care management of adults with
      symptomatic heart failure.

PMID- 9563998
TI  - The new NHS: propaganda 

PMID- 9563996
TI  - The dying child.

PMID- 9563997
TI  - Epidemiological issues in health needs assessment.

PMID- 9563999
TI  - An unusual use of a stethoscope 

PMID- 9564000
TI  - Effectiveness of regional trauma systems. Improvements have occurred since study.

PMID- 9564001
TI  - Has the BMJ discovered an end to ageing? 

PMID- 9564002
TI  - Elder abuse should have been discussed in issue on ageing.

PMID- 9564003
TI  - Recombinant factor VIII may not abolish risk of new variant CJD from factor VIII.

PMID- 9564004
TI  - Who should be liable for funding recombinant factor VIII?

PMID- 9564005
TI  - A Martian view of the Hardinian taboo. Eugenics is flourishing among population
      control groups and intellectual elites.

PMID- 9564006
TI  - GMC must not recommend abolition of united examining Board's examination.

PMID- 9564007
TI  - Prevalence study of carcinoma in situ of testis in oligozoospermic men. Study was
      too small to show potential benefits of screening.

PMID- 9564008
TI  - Care for the growing number of elderly people in developing countries needs to be
      addressed.

PMID- 9564009
TI  - Management of dyspepsia in primary care. GPs are already choosing eradication
      therapy over endoscopy.

PMID- 9564010
TI  - Prion science is not cold fusion.

PMID- 9564011
TI  - Tolerability of alendronate. Comparison group taking placebo should have been
      included.

PMID- 9564012
TI  - Non-steroidal anti-inflammatories should not be used after orthopaedic surgery.

PMID- 9564013
TI  - Patients in east London seem happy to give GPs consent for training.

PMID- 9564015
TI  - John beasley 

PMID- 9564014
TI  - High cost, low volume care in haemophilia.

PMID- 9564017
TI  - The politics of alcoholism in india 

PMID- 9564016
TI  - Death by Injection.

PMID- 9564018
TI  - A view from the other side 

PMID- 9564019
TI  - Textbook of travel medicine and health 

PMID- 9564020
TI  - Current issues in cardiology: management strategies 

PMID- 9564021
TI  - The powerful placebo: from ancient priest to modern physician 

PMID- 9564023
TI  - Father's genes influence risk of pre-eclampsia 

PMID- 9564022
TI  - Survival benefits of fibrinolysis and early aspirin in acute myocardial
      infarction are sustained 

PMID- 9564024
TI  - Integrated case management reduces functional decline and costs in older patients

PMID- 9564025
TI  - Most patients with low back pain have not recovered after a year 

PMID- 9564026
TI  - Most heavy users of sumatriptan take it inappropriately 

PMID- 9564027
TI  - Cardiac rehabilitation is performed poorly in the UK 

PMID- 9564028
TI  - Crystal structure of the catalytic subunit of protein kinase CK2 from Zea mays at
      2.1 A resolution.
AB  - CK2alpha is the catalytic subunit of protein kinase CK2, an acidophilic and
      constitutively active eukaryotic Ser/Thr kinase involved in cell proliferation. A
      crystal structure, at 2.1 A resolution, of recombinant maize CK2alpha
      (rmCK2alpha) in the presence of ATP and Mg2+, shows the enzyme in an active
      conformation stabilized by interactions of the N-terminal region with the
      activation segment and with a cluster of basic residues known as the substrate
      recognition site. The close interaction between the N-terminal region and the
      activation segment is unique among known protein kinase structures and probably
      contributes to the constitutively active nature of CK2. The active centre is
      occupied by a partially disordered ATP molecule with the adenine base attached to
      a novel binding site of low specificity. This finding explains the observation
      that CK2, unlike other protein kinases, can use both ATP and GTP as
      phosphorylating agents.

PMID- 9564029
TI  - Crystal structure of human uroporphyrinogen decarboxylase.
AB  - Uroporphyrinogen decarboxylase (URO-D) catalyzes the fifth step in the heme
      biosynthetic pathway, converting uroporphyrinogen to coproporphyrinogen by
      decarboxylating the four acetate side chains of the substrate. This activity is
      essential in all organisms, and subnormal activity of URO-D leads to the most
      common form of porphyria in humans, porphyria cutanea tarda (PCT). We have
      determined the crystal structure of recombinant human URO-D at 1.60 A resolution.
      The 40.8 kDa protein is comprised of a single domain containing a (beta/alpha)8
      barrel with a deep active site cleft formed by loops at the C-terminal ends of
      the barrel strands. Many conserved residues cluster at this cleft, including the
      invariant side chains of Arg37, Arg41 and His339, which probably function in
      substrate binding, and Asp86, Tyr164 and Ser219, which may function in either
      binding or catalysis. URO-D is a dimer in solution (Kd = 0.1 microM), and this
      dimer also appears to be formed in the crystal. Assembly of the dimer juxtaposes
      the active site clefts of the monomers, suggesting a functionally important
      interaction between the catalytic centers.

PMID- 9564030
TI  - Mechanism of Nef-induced CD4 endocytosis: Nef connects CD4 with the mu chain of
      adaptor complexes.
AB  - The Nef protein of primate lentiviruses down-regulates the cell surface
      expression of CD4 and probably MHC I by connecting these receptors with the
      endocytic machinery. Here, we reveal that Nef interacts with the mu chains of
      adaptor complexes, key components of clathrin-coated pits. For human
      immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV)
      Nef, this interaction occurs via tyrosine-based motifs reminiscent of endocytosis
      signals. Mutating these motifs prevents the binding of SIV Nef to the mu chain of
      plasma membrane adaptor complexes, abrogates its ability to induce CD4
      internalization, suppresses the accelerated endocytosis of a chimeric integral
      membrane protein harboring Nef as its cytoplasmic domain and confers a dominant
      negative phenotype to the viral protein. Taken together, these data identify mu
      adaptins as downstream mediators of the down-modulation of CD4, and possibly MHC
      I, by Nef.

PMID- 9564031
TI  - A dileucine-like sorting signal directs transport into an AP-3-dependent,
      clathrin-independent pathway to the yeast vacuole.
AB  - Transport of yeast alkaline phosphatase (ALP) to the vacuole depends on the
      clathrin adaptor-like complex AP-3, but does not depend on proteins necessary for
      transport through pre-vacuolar endosomes. We have identified ALP sequences that
      direct sorting into the AP-3-dependent pathway using chimeric proteins containing
      residues from the ALP cytoplasmic domain fused to sequences from a Golgi
      localized membrane protein, guanosine diphosphatase (GDPase). The full-length ALP
      cytoplasmic domain, or ALP amino acids 1-16 separated from the transmembrane
      domain by a spacer, directed GDPase chimeric proteins from the Golgi complex to
      the vacuole via the AP-3 pathway. Mutation of residues Leu13 and Val14 within the
      ALP cytoplasmic domain prevented AP-3-dependent vacuolar transport of both
      chimeric proteins and full-length ALP. This Leucine-Valine (LV)-based sorting
      signal targeted chimeric proteins and native ALP to the vacuole in cells lacking
      clathrin function. These results identify an LV-based sorting signal in the ALP
      cytoplasmic domain that directs transport into a clathrin-independent, AP-3
      dependent pathway to the vacuole. The similarity of the ALP sorting signal to
      mammalian dileucine sorting motifs, and the evolutionary conservation of AP-3
      subunits, suggests that dileucine-like signals constitute a core element for AP-3
      dependent transport to lysosomal compartments in all eukaryotic cells.

PMID- 9564032
TI  - TRAPP, a highly conserved novel complex on the cis-Golgi that mediates vesicle
      docking and fusion.
AB  - We previously identified BET3 by its genetic interactions with BET1, a gene whose
      SNARE-like product acts in endoplasmic reticulum (ER)-to-Golgi transport. To gain
      insight into the function of Bet3p, we added three c-myc tags to its C-terminus
      and immunopurified this protein from a clarified detergent extract. Here we
      report that Bet3p is a member of a large complex ( approximately 800 kDa) that we
      call TRAPP (transport protein particle). We propose that TRAPP plays a key role
      in the targeting and/or fusion of ER-to-Golgi transport vesicles with their
      acceptor compartment. The localization of Bet3p to the cis-Golgi complex, as well
      as biochemical studies showing that Bet3p functions on this compartment, support
      this hypothesis. TRAPP contains at least nine other constituents, five of which
      have been identified and shown to be highly conserved novel proteins.

PMID- 9564035
TI  - CIDE, a novel family of cell death activators with homology to the 45 kDa subunit
      of the DNA fragmentation factor.
AB  - DFF45 is a subunit of the DNA fragmentation factor (DFF) that is cleaved by
      caspase-3 during apoptosis. However, the mechanism by which DFF45 regulates
      apoptotic cell death remains poorly understood. Here we report the identification
      and characterization of two mammalian genes, CIDE-A and CIDE-B, encoding highly
      related proteins with homology to the N-terminal region of DFF45. CIDE-A and CIDE
      B were found to activate apoptosis in mammalian cells, which was inhibited by
      DFF45 but not by caspase inhibitors. Expression of CIDE-A induced DNA
      fragmentation in 293T cells, which was inhibited by DFF45, further suggesting
      that DFF45 inhibits the apoptotic activities of CIDEs. In addition to mammalian
      CIDE-A and CIDE-B, we identified DREP-1, a Drosophila melanogaster homolog of
      DFF45 that could inhibit CIDE-A-mediated apoptosis. Mutant analysis revealed that
      the C-terminal region of CIDE-A was necessary and sufficient for killing whereas
      the region with homology to DFF45 located in the N-terminus was required for
      DFF45 to inhibit CIDE-A-induced apoptosis. CD95/Fas-mediated apoptosis was
      enhanced by CIDEs but inhibited by DFF45. These studies suggest that DFF45 is
      evolutionarily conserved and implicate CIDEs as DFF45-inhibitable effectors that
      promote cell death and DNA fragmentation.

PMID- 9564034
TI  - The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle
      inhibitory function induces tumorigenesis.
AB  - The human oncoprotein MDM2 (hMDM2) overexpresses in various human tumors. If
      amplified, the mdm2 gene can enhance the tumorigenic potential of murine cells.
      Here, we present evidence to show that the full-length human or mouse MDM2
      expressed from their respective cDNA can inhibit the G0/G1-S phase transition of
      NIH 3T3 and normal human diploid cells. The protein harbors more than one cell
      cycle-inhibitory domain that does not overlap with the p53-interaction domain.
      Deletion mutants of hMDM2 that lack the cell-cycle-inhibitory domains can be
      stably expressed in NIH 3T3 cells, enhancing their tumorigenic potential. The
      tumorigenic domain of hMDM2 overlaps with the p53-interaction domain. Some tumor
      derived cells, such as Saos-2, H1299 or U-2OS, are relatively insensitive to the
      growth-inhibitory effects of hMDM2. These observations suggest that hMDM2
      overexpression in response to oncogenic stimuli would induce growth arrest in
      normal cells. Elimination or inactivation of the hMDM2-induced G0/G1 arrest may
      contribute to one of the steps of tumorigenesis.

PMID- 9564033
TI  - The Escherichia coli SRP and SecB targeting pathways converge at the translocon.
AB  - Two distinct protein targeting pathways can direct proteins to the Escherichia
      coli inner membrane. The Sec pathway involves the cytosolic chaperone SecB that
      binds to the mature region of pre-proteins. SecB targets the pre-protein to SecA
      that mediates pre-protein translocation through the SecYEG translocon. The SRP
      pathway is probably used primarily for the targeting and assembly of inner
      membrane proteins. It involves the signal recognition particle (SRP) that
      interacts with the hydrophobic targeting signal of nascent proteins. By using a
      protein cross-linking approach, we demonstrate here that the SRP pathway delivers
      nascent inner membrane proteins at the membrane. The SRP receptor FtsY, GTP and
      inner membranes are required for release of the nascent proteins from the SRP.
      Upon release of the SRP at the membrane, the targeted nascent proteins insert
      into a translocon that contains at least SecA, SecY and SecG. Hence, as appears
      to be the case for several other translocation systems, multiple targeting
      mechanisms deliver a variety of precursor proteins to a common membrane
      translocation complex of the E.coli inner membrane.

PMID- 9564036
TI  - Early evolutionary origin of the neurotrophin receptor family.
AB  - Neurotrophins and their Trk receptors play a crucial role in the development and
      maintenance of the vertebrate nervous system, but to date no component of this
      signalling system has been found in invertebrates. We describe a molluscan Trk
      receptor, designated Ltrk, from the snail Lymnaea stagnalis. The full-length
      sequence of Ltrk reveals most of the characteristics typical of Trk receptors,
      including highly conserved transmembrane and intracellular tyrosine kinase
      domains, and a typical extracellular domain of leucine-rich motifs flanked by
      cysteine clusters. In addition, Ltrk has a unique N-terminal extension and lacks
      immunoglobulin-like domains. Ltrk is expressed during development in a stage
      specific manner, and also in the adult, where its expression is confined to the
      central nervous system and its associated endocrine tissues. Ltrk has the highest
      sequence identity with the TrkC mammalian receptor and, when exogenously
      expressed in fibroblasts or COS cells, binds human NT-3, but not NGF or BDNF,
      with an affinity of 2.5 nM. These findings support an early evolutionary origin
      of the Trk family as neuronal receptor tyrosine kinases and suggest that Trk
      signalling mechanisms may be highly conserved between vertebrates and
      invertebrates.

PMID- 9564037
TI  - The Ssn6-Tup1 repressor complex of Saccharomyces cerevisiae is involved in the
      osmotic induction of HOG-dependent and -independent genes.
AB  - The response of yeast to osmotic stress has been proposed to rely on the HOG-MAP
      kinase signalling pathway and on transcriptional activation mediated by STRE
      promoter elements. However, the osmotic induction of HAL1, an important
      determinant of salt tolerance, is HOG independent and occurs through the release
      of transcriptional repression. We have identified an upstream repressing sequence
      in HAL1 promoter (URSHAL1) located between -231 and -156. This promoter region
      was able to repress transcription from a heterologous promoter and to bind
      proteins in non-stressed cells, but not in salt-treated cells. The repression
      conferred by URSHAL1 is mediated through the Ssn6-Tup1 protein complex and is
      abolished in the presence of osmotic stress. The Ssn6-Tup1 co-repressor is also
      involved in the regulation of HOG-dependent genes such as GPD1, CTT1, ALD2, ENA1
      and SIP18, and its deletion can suppress the osmotic sensitivity of hog1 mutants.
      We propose that the Ssn6-Tup1 repressor complex might be a general component in
      the regulation of osmostress responses at the transcriptional level of both HOG
      dependent and -independent genes.

PMID- 9564039
TI  - Glucose sensing and signaling by two glucose receptors in the yeast Saccharomyces
      cerevisiae.
AB  - How eukaryotic cells sense availability of glucose, their preferred carbon and
      energy source, is an important, unsolved problem. Bakers' yeast (Saccharomyces
      cerevisiae) uses two glucose transporter homologs, Snf3 and Rgt2, as glucose
      sensors that generate a signal for induction of expression of genes encoding
      hexose transporters (HXT genes). We present evidence that these proteins generate
      an intracellular glucose signal without transporting glucose. The Snf3 and Rgt2
      glucose sensors contain unusually long C-terminal tails that are predicted to be
      in the cytoplasm. These tails appear to be the signaling domains of Snf3 and Rgt2
      because they are necessary for glucose signaling by Snf3 and Rgt2, and
      transplantation of the C-terminal tail of Snf3 onto the Hxt1 and Hxt2 glucose
      transporters converts them into glucose sensors that can generate a signal for
      glucose-induced HXT gene expression. These results support the idea that yeast
      senses glucose using two modified glucose transporters that serve as glucose
      receptors.

PMID- 9564038
TI  - Insulin regulates the dynamic balance between Ras and Rap1 signaling by
      coordinating the assembly states of the Grb2-SOS and CrkII-C3G complexes.
AB  - Insulin stimulation of Chinese hamster ovary cells expressing the human insulin
      receptor resulted in a time-dependent decrease in the amount of GTP bound to
      Rap1. The inactivation of Rap1 was associated with an insulin-stimulated decrease
      in the amount of Rap1 that was bound to Raf1. In parallel with the dissociation
      of Raf1 from Rap1, there was an increased association of Raf1 with Ras.
      Concomitant with the inactivation of Rap1 and decrease in Rap1-Raf1 binding, we
      observed a rapid insulin-stimulated dissociation of the CrkII-C3G complex which
      occurred in a Ras-independent manner. The dissociation of the CrkII-C3G was
      recapitulated in vitro using a GST-C3G fusion protein to precipitate CrkII from
      whole cell detergent extracts. The association of GST-C3G with CrkII was also
      dose dependent and demonstrated that insulin reduced the affinity of CrkII for
      C3G without any effect on CrkII protein levels. Furthermore, the reduction in
      CrkII binding affinity was reversible by tyrosine dephosphorylation with PTP1B
      and by mutation of Tyr221 to phenylalanine. Together, these data demonstrate that
      insulin treatment results in the de-repression of Rap1 inhibitory function on the
      Raf1 kinase concomitant with Ras activation and stimulation of the downstream
      Raf1/MEK/ERK cascade.

PMID- 9564040
TI  - Angiotensin II stimulates ERK via two pathways in epithelial cells: protein
      kinase C suppresses a G-protein coupled receptor-EGF receptor transactivation
      pathway.
AB  - In GN4 rat liver epithelial cells, angiotensin II (Ang II) produces intracellular
      calcium and protein kinase C (PKC) signals and stimulates ERK and JNK activity.
      JNK activation appears to be mediated by a calcium-dependent tyrosine kinase
      (CADTK). To define the ERK pathway, we established GN4 cells expressing an
      inhibitory Ras(N17). Induction of Ras(N17) blocked EGF- but not Ang II- or
      phorbol ester (TPA)-dependent ERK activation. In control cells, Ang II and TPA
      produced minimal increases in Ras-GTP level and Raf kinase activity. PKC
      depletion by chronic TPA exposure abolished TPA-dependent ERK activation but
      failed to diminish the effect of Ang II. In PKC-depleted cells, Ang II increased
      Ras-GTP level and activated Raf and ERK in a Ras-dependent manner. In PKC
      depleted cells, Ang II stimulated Shc and Cbl tyrosine phosphorylation,
      suggesting that without PKC, Ang II activates another tyrosine kinase. PKC
      depletion did not alter Ang II-dependent tyrosine phosphorylation or activity of
      p125(FAK), CADTK, Fyn or Src, but PKC depletion or incubation with GF109203X
      resulted in Ang II-dependent EGF receptor tyrosine phosphorylation. In PKC
      depleted cells, EGF receptor-specific tyrosine kinase inhibitors blocked Ang II
      dependent EGF receptor and Cbl tyrosine phosphorylation, and ERK activation. In
      summary, Ang II can activate ERK via two pathways; the latent EGF receptor, Ras
      dependent pathway is equipotent to the Ras-independent pathway, but is masked by
      PKC action. The prominence of this G-protein coupled receptor to EGF receptor
      pathway may vary between cell types depending upon modifiers such as PKC.

PMID- 9564041
TI  - A unique insert in the linker domain of Syk is necessary for its function in
      immunoreceptor signalling.
AB  - Accumulating data indicate that the 'linker' region of Syk, which lies between
      its tandem Src homology 2 (SH2) domains and kinase region, provides a critical
      function for the biological activity of Syk. This importance has been ascribed to
      the presence of tyrosine phosphorylation sites capable of mediating the
      recruitment of cellular effectors. We and others previously identified an
      alternatively spliced variant of Syk, termed SykB, which lacks a 23 amino acid
      sequence in the linker domain. As this 'linker insert' is also not present in the
      closely related enzyme Zap-70, it seems plausible that Syk possesses this unique
      sequence for functional reasons. To understand its role better, we have compared
      the abilities of Syk and SykB to participate in immunoreceptor-triggered signal
      transduction. The results of our experiments revealed that, unlike Syk, SykB was
      inefficient at coupling stimulation of FcepsilonRI on basophils or the antigen
      receptor on T cells to the early and late events of cellular activation. Further
      studies showed that the functional defect in SykB was not caused by the absence
      of crucial tyrosine phosphorylation sites, or by a reduced intrinsic kinase
      activity. Rather, it correlated with the reduced ability of SykB to bind
      phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) in vitro
      and in vivo. In combination, these results demonstrated that the unique insert in
      the linker domain of Syk is crucial for its capacity to participate in
      immunoreceptor signalling. Furthermore, they provided evidence that the linker
      region can regulate the ability of Syk to bind ITAMs, thus identifying a novel
      function for this domain.

PMID- 9564042
TI  - Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase
      (ASK) 1.
AB  - Apoptosis signal-regulating kinase (ASK) 1 was recently identified as a mitogen
      activated protein (MAP) kinase kinase kinase which activates the c-Jun N-terminal
      kinase (JNK) and p38 MAP kinase pathways and is required for tumor necrosis
      factor (TNF)-alpha-induced apoptosis; however, the mechanism regulating ASK1
      activity is unknown. Through genetic screening for ASK1-binding proteins,
      thioredoxin (Trx), a reduction/oxidation (redox)-regulatory protein thought to
      have anti-apoptotic effects, was identified as an interacting partner of ASK1.
      Trx associated with the N-terminal portion of ASK1 in vitro and in vivo.
      Expression of Trx inhibited ASK1 kinase activity and the subsequent ASK1
      dependent apoptosis. Treatment of cells with N-acetyl-L-cysteine also inhibited
      serum withdrawal-, TNF-alpha- and hydrogen peroxide-induced activation of ASK1 as
      well as apoptosis. The interaction between Trx and ASK1 was found to be highly
      dependent on the redox status of Trx. Moreover, inhibition of Trx resulted in
      activation of endogenous ASK1 activity, suggesting that Trx is a physiological
      inhibitor of ASK1. The evidence that Trx is a negative regulator of ASK1 suggests
      possible mechanisms for redox regulation of the apoptosis signal transduction
      pathway as well as the effects of antioxidants against cytokine- and stress
      induced apoptosis.

PMID- 9564043
TI  - Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase.
AB  - Infection of a cell by human immunodeficiency virus type 1 (HIV-1) results in the
      formation of a reverse transcription complex in which viral nucleic acids are
      synthesized. Efficient disengagement of the reverse transcription complex from
      the cell membrane and subsequent nuclear translocation require phosphorylation of
      reverse transcription complex components by a virion-associated kinase. In this
      study, we identify the virion-associated kinase as mitogen-activated protein
      kinase (ERK/MAPK). Upon density gradient fractionation, MAPK, but not its
      activating kinase MEK, co-sedimented with viral particles. Expression of a
      constitutively active, but not kinase-inactive, MEK1 in virus producer cells was
      able to activate virion-associated MAPK in trans. Stimulation of virion
      associated MAPK activity in trans by the mitogen phorbol myristate acetate (PMA)
      increased viral infectivity. Conversely, suppression of virion-associated MAPK by
      specific inhibitors of the MAPK cascade markedly impaired viral infectivity.
      These studies demonstrate regulation of an early step in HIV-1 infection by the
      host cell MAPK signal transduction pathway.

PMID- 9564044
TI  - A mitogen-activated protein (MAP) kinase homologue of Leishmania mexicana is
      essential for parasite survival in the infected host.
AB  - The parasitic protozoon Leishmania mexicana undergoes two major developmental
      stages in its life cycle exhibiting profound physiological and morphological
      differences, the promastigotes in the insect vector and the amastigotes in
      mammalian macrophages. A deletion mutant, Deltalmsap1/2, for the secreted acid
      phosphatase (SAP) gene locus, comprising the two SAP genes separated by an
      intergenic region of approximately 11.5 kb, lost its ability to cause a
      progressive disease in Balb/c mice. While in vitro growth of promastigotes,
      invasion of host cells and differentiation from promastigotes to amastigotes was
      indistinguishable from the wild-type, the mutant parasites ceased to proliferate
      when transformed to amastigotes in infected macrophages or in a macrophage-free
      in vitro differentiation system, suggesting a stage-specific growth arrest. This
      phenotype could be reverted by complementation with 6 kb of the intergenic region
      of the SAP gene locus. Sequence analysis identified two open reading frames, both
      encoding single copy genes; one gene product shows high homology to mitogen
      activated protein (MAP) kinases. Complementation experiments revealed that the
      MAP kinase homologue, designated LMPK, is required and is sufficient to restore
      the infectivity of the Deltalmsap1/2 mutant. Therefore, LMPK is a kinase that is
      essential for the survival of L.mexicana in the infected host by affecting the
      cell division of the amastigotes.

PMID- 9564045
TI  - The redox-regulated SoxR protein acts from a single DNA site as a repressor and
      an allosteric activator.
AB  - The SoxR protein of Escherichia coli responds to redox signals by activating the
      transcription of soxS, which encodes another transcription activator that
      directly stimulates oxidative stress genes. We show here that transcription of
      the soxR gene, which is positioned head-to-head with soxS in the chromosome,
      initiates in the intergenic region and is itself repressed by SoxR protein in in
      vitro transcription experiments. Analysis of single-copy operon fusions to soxR,
      combined with the results of Northern blotting experiments, verified this
      regulation and the transcription start site in vivo. The structure of the
      overlapping promoters is such that the single SoxR-binding site is located in the
      -10/-35 spacer of the soxS promoter, but just downstream of the -10 element of
      the soxR promoter. Activated and non-activated SoxR bind this site equally well,
      exerting nearly constant repression of soxR; activated SoxR simultaneously
      stimulates the soxS promoter >/=30-fold. The functional soxR promoter depresses
      soxS transcription when SoxR is not activated and enhances soxS transcription
      when SoxR is activated, as shown by comparing the expression of soxS'::lacZ
      fusions with and without the soxR -35 element (induction ratio only approximately
      7-fold). SoxR thus represents a highly polar, redox-regulated transcriptional
      switch that maximizes the change in expression of soxS.

PMID- 9564046
TI  - Selection in vitro of novel ribozymes from a partially randomized U2 and U6 snRNA
      library.
AB  - Combinatorial libraries related to spliceosomal U2 and U6 snRNAs were tested for
      catalytic reactions typical of the splicing of nuclear pre-mRNAs. Ribozymes with
      four different activities were selected based on covalent bond formation to a
      substrate RNA. The first activity was reversible self-cleavage; ribozymes self
      cleaved then ligated the 5'-hydroxyl group of the substrate oligonucleotide to
      their 2',3'-cyclic phosphate intermediate. The second activity was 2',5'-branch
      formation by the attack of a substrate 2'-hydroxyl group on the 5'-terminal
      triphosphate of the ribozyme transcript, releasing pyrophosphate. The third
      ribozyme activity was similar to reversible self-cleavage but was a three-step
      reaction. This ribozyme self-cleaved, then cleaved the substrate in trans, and
      then ligated the substrate 3' cleavage product to its cyclic phosphate
      intermediate. This three-step pathway shares similarities with the pathway of
      tRNA splicing. The fourth activity was 2',3'-branch formation; to form this
      unusual branch, a 2'-hydroxyl of the substrate attacked an internal phosphate of
      the ribozyme, releasing an oligonucleotide leaving group. The isolation of
      branching activities by the in vitro selection protocol was unanticipated and was
      due to surprising properties of reverse transcriptase, which can read through
      2',5'- or 2',3'-branches and efficiently perform non-templated intramolecular
      jumps.

PMID- 9564047
TI  - Dbp5p, a cytosolic RNA helicase, is required for poly(A)+ RNA export.
AB  - The DBP5 gene encodes a putative RNA helicase of unknown function in the yeast
      Saccharomyces cerevisiae. It is shown here that Dbp5p is an ATP-dependent RNA
      helicase required for polyadenylated [poly(A)+] RNA export. Surprisingly, Dbp5p
      is present predominantly, if not exclusively, in the cytoplasm, and is highly
      enriched around the nuclear envelope. This observation raises the possibility
      that Dbp5p may play a role in unloading or remodeling messenger RNA particles
      (mRNPs) upon arrival in the cytoplasm and in coupling mRNP export and
      translation. The functions of Dbp5p are likely to be conserved, since its
      potential homologues can be found in a variety of eukaryotic cells.

PMID- 9564049
TI  - hMSH2 and hMSH6 play distinct roles in mismatch binding and contribute
      differently to the ATPase activity of hMutSalpha.
AB  - In extracts of human cells, base-base mismatches and small insertion/deletion
      loops are bound primarily by hMutSalpha, a heterodimer of hMSH2 and hMSH6 (also
      known as GTBP or p160). Recombinant hMutSalpha bound a G/T mismatch-containing
      oligonucleotide with an apparent dissociation constant Kd = 2.6 nM, while its
      affinity for a homoduplex substrate was >20-fold lower. In the presence of ATP,
      hMutSalpha dissociated from mismatched oligonucleotide substrates, and this
      reaction was attenuated by mutating the conserved lysine in the ATP-binding
      domains of hMSH6, hMSH2 or both to arginine. Surprisingly, this reaction required
      only ATP binding, not hydrolysis. The ATPase activity of hMutSalpha variants
      carrying the Lys-->Arg mutation in hMSH2 or in hMSH6 was severely affected, but
      these mutants were still proficient in mismatch binding and were able to
      complement, albeit to different extents, mismatch repair-deficient cell extracts.
      The mismatch binding-proficient, ATPase-deficient double mutant was inactive in
      the complementation assay and its presence in repair-proficient extracts was
      inhibitory. We conclude that although the ATPase activity of hMutSalpha is
      dispensible for mismatch binding, it is required for mismatch correction.

PMID- 9564048
TI  - Dbp5p/Rat8p is a yeast nuclear pore-associated DEAD-box protein essential for RNA
      export.
AB  - To identify Saccharomyces cerevisiae genes important for nucleocytoplasmic export
      of messenger RNA, we screened mutant strains to identify those in which poly(A)+
      RNA accumulated in nuclei under nonpermissive conditions. We describe the
      identification of DBP5 as the gene defective in the strain carrying the rat8-1
      allele (RAT = ribonucleic acid trafficking). Dbp5p/Rat8p, a previously
      uncharacterized member of the DEAD-box family of proteins, is closely related to
      eukaryotic initiation factor 4A(eIF4A) an RNA helicase essential for protein
      synthesis initiation. Analysis of protein databases suggests most eukaryotic
      genomes encode a DEAD-box protein that is probably a homolog of yeast
      Dbp5p/Rat8p. Temperature-sensitive alleles of DBP5/RAT8 were prepared. In rat8
      mutant strains, cells displayed rapid, synchronous accumulation of poly(A)+ RNA
      in nuclei when shifted to the non-permissive temperature. Dbp5p/Rat8p is located
      within the cytoplasm and concentrated in the perinuclear region. Analysis of the
      distribution of Dbp5p/Rat8p in yeast strains where nuclear pore complexes are
      tightly clustered indicated that a fraction of this protein associates with
      nuclear pore complexes (NPCs). The strong mutant phenotype, association of the
      protein with NPCs and genetic interaction with factors involved in RNA export
      provide strong evidence that Dbp5p/Rat8p plays a direct role in RNA export.

PMID- 9564050
TI  - RAD9 and RAD24 define two additive, interacting branches of the DNA damage
      checkpoint pathway in budding yeast normally required for Rad53 modification and
      activation.
AB  - In budding yeast, RAD9 and RAD24/RAD17/MEC3 are believed to function upstream of
      MEC1 and RAD53 in signalling the presence of DNA damage. Deletion of any one of
      these genes reduces the normal G1/S and G2/M checkpoint delays after UV
      irradiation, whereas in rad9Delta-rad24Delta cells the G1/S checkpoint is
      undetectable, although there is a residual G2/M checkpoint. We have shown
      previously that RAD9 also controls the transcriptional induction of a DNA damage
      regulon (DDR). We now report that efficient DDR induction requires all the above
      mentioned checkpoint genes. Residual induction of the DDR after UV irradiation
      observed in all single mutants is not detectable in rad9Delta-rad24Delta. We have
      examined the G2/M checkpoint and UV sensitivity of single mutants after
      overexpression of the checkpoint proteins. This analysis indicates that RAD9 and
      the RAD24 epistasis group can be placed onto two separate, additive branches that
      converge on MEC1 and RAD53. Furthermore, MEC3 appears to function downstream of
      RAD24/RAD17. The transcriptional response to DNA damage revealed unexpected and
      specific antagonism between RAD9 and RAD24. Further support for genetic
      interaction between RAD9 and RAD24 comes from study of the modification and
      activation of Rad53 after damage. Evidence for bypass of RAD53 function under
      some conditions is also presented.

PMID- 9564052
TI  - Hydration and recognition of methylated CpG steps in DNA.
AB  - The analysis of the hydration pattern around methylated CpG steps in three high
      resolution (1.7, 2.15 and 2.2 A) crystal structures of A-DNA decamers reveals
      that the methyl groups of cytosine residues are well hydrated. In comparing the
      native structure with two structurally distinct forms of the decamer
      d(CCGCCGGCGG) fully methylated at its CpG steps, this study shows also that in
      certain structural and sequence contexts, the methylated cytosine base can be
      more hydrated that the unmodified one. These water molecules seem to be
      stabilized in front of the methyl group through the formation C-H...O
      interactions. In addition, these structures provide the first observation of
      magnesium cations bound to the major groove of A-DNA and reveal two distinct
      modes of metal binding in methylated and native duplexes. These findings suggest
      that methylated cytosine bases could be recognized by protein or DNA polar
      residues through their tightly bound water molecules.

PMID- 9564051
TI  - Efficient HIV-1 replication can occur in the absence of the viral matrix protein.
AB  - Matrix (MA), a major structural protein of retroviruses, is thought to play a
      critical role in several steps of the HIV-1 replication cycle, including the
      plasma membrane targeting of Gag, the incorporation of envelope (Env)
      glycoproteins into nascent particles, and the nuclear import of the viral genome
      in non-dividing cells. We now show that the entire MA protein is dispensable for
      the incorporation of HIV-1 Env glycoproteins with a shortened cytoplasmic domain.
      Furthermore, efficient HIV-1 replication in the absence of up to 90% of MA was
      observed in a cell line in which the cytoplasmic domain of Env is not required.
      Additional compensatory changes in Gag permitted efficient virus replication even
      if all of MA was replaced by a heterologous membrane targeting signal. Viruses
      which lacked the globular domain of MA but retained its N-terminal myristyl
      anchor exhibited an increased ability to form both extracellular and
      intracellular virus particles, consistent with a myristyl switch model of Gag
      membrane targeting. Pseudotyped HIV-1 particles that lacked the structurally
      conserved globular head of MA efficiently infected macrophages, indicating that
      MA is dispensable for nuclear import in terminally differentiated cells.

PMID- 9564053
TI  - Swimming lessons--check the water before jumping in.

PMID- 9564054
TI  - 1997 AAGL membership survey: practice profiles.

PMID- 9564056
TI  - Long-term follow-up of endometrial ablation.
AB  - STUDY OBJECTIVE: To assess long-term outcome of endometrial ablation for
      treatment of menorrhagia. DESIGN: Five-year, prospective longitudinal study
      (Canadian Task Force classification II=1). SETTING: University teaching hospital.
      PATIENTS: The first 301 women in a continuing series of over 550 patients
      undergoing hysteroscopic endometrial ablation. INTERVENTION: Hysteroscopic
      endometrial ablation. MEASUREMENTS AND MAIN RESULTS: Patients were followed at
      regular intervals for 24 to 60 months (mean 28 mo). Outcomes were reported in
      terms of control of menstrual blood loss and menstrual pain with respect to
      normal uterus, fibroid uterus, dysmenorrhea, and patient age. CONCLUSION:
      Hysteroscopic endometrial ablation is effective for relief of menorrhagia and
      associated dysmenorrhea in selected patients. Success may decline with increasing
      length of follow-up.

PMID- 9564055
TI  - Prevention and management of urinary tract injury in laparoscopic surgery.

PMID- 9564057
TI  - Endometrial Na+, K+-ATPase pump function and vasopressin levels during
      hysteroscopic surgery in patients pretreated with GnRH agonist.
AB  - STUDY OBJECTIVE: To investigate the effects of gonadotropin-releasing hormone
      (GnRH) analog pretreatment on endometrial Na+, K+-adenosine triphosphatase
      (ATPase) pump function and peripheral blood vasopressin levels, and their role in
      fluid absorption and mechanisms of hyponatremia in patients undergoing
      hysteroscopic endometrial ablation. DESIGN: Prospective, randomized, placebo
      controlled study (Canadian Task Force classification I). SETTING: University
      affiliated hospital. PATIENTS: Seventeen women with dysfunctional uterine
      bleeding. INTERVENTION: Nine women received a GnRH analog and eight received
      saline approximately 6 to 8 weeks before hysteroscopic ablation by
      electrosurgery. MEASUREMENTS AND MAIN RESULTS: Both before randomization and
      immediately before surgery, endometrial biopsy samples were obtained and numbered
      consecutively without patient identification. Operative hysteroscopy was
      performed with glycine 1.5% mixed with 2% alcohol. The amount of irrigant and
      irrigant deficit; blood levels of albumin and ethanol; hematocrit and hemoglobin;
      changes in sodium levels; and central venous pressure were compared. The Na+, K+
      ATPase pump activity was significantly increased in the GnRH analog group
      compared with the saline group and correlated with decreased estradiol levels
      (0.4 +/- 0.08 vs 0.26 +/- 0.06 micro mol/min/ml). Vasopressin levels were
      significantly lower in the GnRH group (3.2 +/- 0.9 vs 7.6 +/- 1.7 micro mol/L).
      Mean volume of irrigant used and operating time were similar in both groups.
      Volume deficit, decrease in protein, and hematocrit were less in GnRH than in the
      saline group. Blood ethanol levels, decrease in sodium, and irrigant deficit were
      significantly lower in GnRH group. CONCLUSION: Pretreatment with GnRH analogs may
      prevent the adverse effects of estradiol on endometrial Na+, K+-ATPase and
      creates a protective mechanism against iatrogenic hyponatremia, which is more
      critical in women than men in case of absorption of irrigating fluid. Moreover,
      created hypoestrogenism may enhance Na+, K+-ATPase activity in brain as well as
      endometrium, thus decreasing women's susceptibility to hyponatremic complications
      and brain damage. Suppressed vasopressin levels may be protective against fluid
      absorption in GnRH analog-treated patients.

PMID- 9564058
TI  - Measurement of intraocular pressure during laparoscopy and its relationship to
      central venous pressure.
AB  - STUDY OBJECTIVE. To determine the effect of different positional degrees on
      hemodynamics, especially central venous pressure and intraocular pressure, and a
      possible interrelationship, during laparoscopic surgery. SETTING. University
      teaching hospital (Canadian Task Force classification II-1). PATIENTS: Seven
      women undergoing elective gynecologic laparoscopy. INTERVENTIONS: The women were
      monitored for heart rate, partial pressure of oxygen, end-tidal carbon dioxide,
      arterial blood pressure, central venous pressure, end-tidal isoflurane
      concentration, and intraocular pressure in several body positions during general
      anesthesia. MEASUREMENTS AND MAIN RESULTS: Intraocular pressure depends on body
      position (r2 = 0.58) related to central venous pressure (r2 = 0.7). Heart rate
      and arterial blood pressure are also dependent on the body position, but to a
      lesser degree. CONCLUSION: Continuous monitoring of intraocular pressure may help
      detect alterations in central venous pressure during general anesthesia for
      laparoscopic surgery. Undesirable alterations caused by degree of Trendelenburg
      position may negatively affect patients with high cardiac or ophthalmic risk.

PMID- 9564059
TI  - The effects of duration of CO2 insufflation and irrigation on peritoneal
      microcirculation assessed by free radical scavengers and total glutathion levels
      during operative laparoscopy.
AB  - STUDY OBJECTIVE: To investigate the effects of peritoneal exposure to carbon
      dioxide (CO2) on peritoneal microcirculation and free radical scavenger (FRS)
      metabolism, and its role in potential adhesion formation after operative
      laparoscopy. DESIGN: Randomized, controlled study (Canadian Task Force
      classification I). SETTING: University-affiliated hospital. PATIENTS: Twenty
      eight women undergoing operative laparoscopy for adnexal masses. INTERVENTION:
      For each patient, a 1 x 1-cm sidewall peritoneal flap was excised at the end of
      laparoscopy and numbered randomly. Similar flaps obtained from 24 women
      immediately after entering the abdomen during laparotomy served as controls.
      MEASUREMENTS AND MAIN RESULTS: Changes in glutathione peroxidase (GSH-Px),
      superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were
      studied in homogenized peritoneal tissues. The duration of CO2 exposure and
      amount of CO2 used were correlated with levels of free radical scavengers and
      compared with controls. Mean CO2 exposure, amount of CO2 used, and CO2 pressure
      (15 mm Hg) was similar between low irrigation and irrigated laparoscopy (118.3 +/
      25 and 39.2 +/- 8.81 min and 125 +/- 20 and 44.5 +/- 6.81 min, respectively).
      The change in FRS levels was significantly correlated with duration and amount of
      CO2 exposure (r = -0.92). Levels of GSH-Px, SOD, CAT, and GSH were significantly
      lower in the CO2 exposure group than in controls (0.57 micro mol, 1.8 ng, 48.5
      micro mol, 1.5 nmol vs 0.8 micro mol, 2.6 +/- 0.4 ng, 79 micro mol, 3.6 nmol,
      respectively). CONCLUSION: Exposure to CO2 has adverse effects on peritoneal
      microcirculation and cell-protective systems, which are proposed mechanisms in
      adhesion formation. Avoiding long CO2 exposure and copiously irrigating the
      abdominal cavity throughout surgery may lessen these effects. The potential role
      of the peritoneal FRS system on postoperative adhesion formation and its relation
      to estrogen status mandates further studies.

PMID- 9564060
TI  - Laparoscopic appraisal of the anatomic relationship of the umbilicus to the
      aortic bifurcation.
AB  - STUDY OBJECTIVE: To determine the cephalocaudal relationship among the umbilicus,
      aortic bifurcation, and iliac vessels by direct measurement during laparoscopy.
      DESIGN: Prospective, consecutive study (Canadian Task Force classification II-1).
      SETTING: Tertiary referral center. PATIENTS: Ninety-seven women undergoing
      operative laparoscopy. INTERVENTIONS: The distance from the aortic bifurcation
      relative to the umbilicus was measured in both the supine and Trendelenburg
      positions with a marked suction-irrigator probe. Patients were stratified into
      three groups based on body mass index (kg/m2). The anatomic location of the
      common iliac vessels and course of the left common iliac vein were identified in
      68 women. MEASUREMENTS AND MAIN RESULTS: The position of the aortic bifurcation
      ranged from 5 cm cephalad to 3 cm caudal to the umbilicus in the supine position,
      and from 3 cm cephalad to 3 cm caudal in the Trendelenburg position. In the
      supine position, the aortic bifurcation was located caudal to the umbilicus in
      only 11% of patients compared with 33% in the Trendelenburg position. This
      difference was statistically significant for the total study population (p
      <0.0001) and for the nonoverweight group (p <0.01). In both positions no
      significant correlation was found between the distance from the aortic
      bifurcation to the umbilicus and body mass index. Mean +/- SD distance of the
      aortic bifurcation from the umbilicus in the supine position was 0.1 +/- 1.2 cm
      for the nonoverweight group, 0.7 +/- 1.5 cm for the overweight group, and 1. 2 +/
      1.5 cm for the very overweight group. Respective values in Trendelenburg
      position were 1.0 +/- 1.1, -0.4 +/- 1.2, and -0.2 +/- 1.3 cm. The common iliac
      artery was caudal to the umbilicus in four women. The space between common iliac
      arteries was always at least partly occupied by the left common iliac vein, and
      was completely filled in 19 women (28%). CONCLUSIONS: The cephalocaudal
      relationship between the aortic bifurcation and umbilicus varies widely and is
      not related to body mass index in anesthetized patients. Regardless of body mass
      index, the aortic bifurcation is more likely to be located caudal to the
      umbilicus in the Trendelenburg compared with the supine position. Its presumed
      location can be misleading during Veress needle or primary cannula insertion, and
      a more reliable guide is necessary for this procedure to avoid major
      retroperitoneal vascular injury.

PMID- 9564061
TI  - In vivo detection of metastatic ovarian cancer by means of 5-aminolevulinic acid
      induced fluorescence in a rat model.
AB  - STUDY OBJECTIVES: To determine the feasibility of macroscopic visualization of
      small ovarian cancer metastases in vivo by fluorescence after intravenous
      administration of 5-aminolevulinic acid (ALA); to assess the time after drug
      injection when fluorescence of small metastases is maximum; and to correlate
      macroscopic in vivo fluorescence with both microscopic ex vivo fluorescence and
      histologic findings. DESIGN: Controlled animal study (Canadian Task Force
      classification I). SETTING: University-based facility. SUBJECTS: Twenty-four
      healthy, female Fischer rats. INTERVENTION: Diffuse peritoneal metastatic cancer
      was induced in Fischer 344 rats by intraperitoneal injection of 1 million
      syngeneic ovarian cancer cells (NuTu-19). Four weeks after induction ALA100 mg/kg
      was injected intravenously, and diagnostic laparotomy was performed 1, 3, 6, or 9
      hours thereafter. MEASUREMENTS AND MAIN RESULTS: The peritoneal cavity was
      illuminated with the Wood's lamp (ultraviolet light). Fluorescence was determined
      by direct visualization and compared with a calibrated fluorescent disk. Tissues
      were collected, sectioned, and examined by fluorescence and conventional light
      microscopy. Within 1 to 3 hours after intravenous injection of ALA, in vivo
      fluorescence of tumor nodules (diameter 0.4-5.0 mm) was macroscopically visible.
      Tumor-free peritoneum did not show fluorescence and was significantly
      distinguishable from cancer nodules. Fluorescence from intestinal tissues was
      comparable with tumor nodules. Microscopic fluorescence analysis showed similar
      values for tumor nodules and peritoneum. Stained histologic specimens of
      peritoneal surface revealed a superficial layer of cancer cells responsible for
      fluorescence. The time course of the fluorescence curve in the intestine peaked
      twice, at 1 and 6 hours after ALA injection. Macroscopically fluorescing nodules
      were histology confirmed as malignant. CONCLUSIONS: Fluorescence detection of
      small cancer nodules after intravenous injection of ALA is feasible for nodules
      smaller than 0.5 mm on the peritoneum. One to 3 hours after drug injection is
      optimal for diagnosis of metastases.

PMID- 9564062
TI  - A randomized, prospective comparison of pain after gasless laparoscopy and
      traditional laparoscopy.
AB  - STUDY OBJECTIVE: To compare pain after laparoscopic tubal ligation by gasless
      laparoscopy versus carbon dioxide (CO2) pneumoperitoneum. DESIGN: Prospective,
      randomized, single-blind comparison (Canadian Task Force classification I).
      SETTING: Private obstetric-gynecology hospital associated with a university
      resident teaching program. PATIENTS: Women age 21 to 42. INTERVENTION: Single
      puncture laparoscopic tubal ligation was performed with a silicone elastomer
      band. Gasless laparoscopy was performed with a Laprolift and traditional
      laparoscopy with CO2 pneumoperitoneum. Postoperative pain in the shoulder and
      periumbilical and lower pelvic regions was measured by visual analog scale on the
      day of surgery and postoperative days 1, 2, 3, 7, and 14. MEASUREMENTS AND MAIN
      RESULTS: Of the 67 patients, 54 provided visual analog scales for analysis, 30 in
      the gasless group and 24 in the traditional group. No statistical difference was
      seen in scores for shoulder, periumbilical, and pelvic pain between techniques.
      CONCLUSION: Patients undergoing gasless laparoscopy and traditional laparoscopy
      experience similar postoperative pain.

PMID- 9564063
TI  - Myometrial tissue in uterine septa.
AB  - STUDY OBJECTIVE: To assess the frequency of myometrial tissue in the septa of
      septate uteri. DESIGN: Retrospective review (Canadian Task Force classification
      II-2). SETTING: University-affiliated tertiary referral center. PATIENTS: Twenty
      nine consecutive women with uterine septa diagnosed by magnetic resonance imaging
      (MRI). INTERVENTIONS: The MRI examination was performed with a 1.5 Tesla scanner
      using high-resolution phased array coils with multiplanar fast-spin echo and T1
      weighted sequences. Of resected septa, tissue was available in four for
      histologic evaluation for the presence of myometrial tissue. MEASUREMENTS AND
      MAIN RESULTS: In 17 women MRI showed a partial septum, all containing myometrium.
      The 12 patients with complete septum had evidence of myometrium in the upper part
      of the septum, with fibrous tissue constituting the lower part. Histology
      reviewed from four resected septa (2 partial, 2 complete) reported myometrial
      tissue. CONCLUSION: Uterine septa are frequently composed of myometrial tissue.

PMID- 9564064
TI  - Pain control after microlaparoscopy.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of intraperitoneal subdiaphragmatic
      instillation of 0.5% lidocaine and 0.5% bupivacaine infiltration of cannula sites
      to control pain after diagnostic microlaparoscopy. DESIGN: Prospective,
      randomized study. (Canadian Task Force classification I). SETTING: Day surgery
      unit of Endogyn Service, Private Endoscopic Associates, Naples, and Department of
      Gynecologic and Pediatric Sciences, Reggio Calabria University, Catanzaro, Italy.
      PATIENTS: Forty women treated for infertility. INTERVENTIONS: The treated group
      received 0.5% intraperitoneal subdiaphragmatic lidocaine 40 ml and 0.5%
      bupivacaine 5 ml infiltration of cannula insertion sites. The control group
      received no treatment. In all patients the procedure was performed with atropine
      0.5 mg, fentanyl 0.1 mg, droperidol 5 mg, and local anesthesia. Postoperatively,
      depending on the need, ketoprofene 100 mg or ketorolac 30 mg was administered
      intramuscularly. MEASUREMENTS AND MAIN RESULTS: Postoperative pain score was
      evaluated by visual analog scale immediately postoperatively and 1, 3, 6, 12, 24,
      36, and 48 hours afterward. The treated group had significantly lower pain scores
      at the end of surgery and at 1-, 3-, (p <0.01), and 6-hour intervals (p <0.05).
      No significant differences in scores between groups were observed starting from 6
      hours postoperatively. CONCLUSION: Postoperative intraperitoneal lidocaine and
      bupivacaine infiltration of cannula sites offered a detectable benefit to women
      undergoing diagnostic microlaparoscopy. The effect was temporary, but induced a
      significant decrease in the postoperative pain for approximately 6 hours.

PMID- 9564065
TI  - Laparoscopic conservative excision of ovarian dermoid cysts with and without an
      endobag.
AB  - STUDY OBJECTIVE: To compare outcomes of conservative laparoscopic treatment of
      dermoid cysts removed from the abdominal cavity without (group A) and with an
      endobag (group B). DESIGN: Prospective, randomized, 4-year (June 1992-June 1996)
      study (Canadian Task Force classification I). SETTING: Department of Obstetrics
      and Gynecology of the Catholic University of the Sacred Heart in Rome. PATIENTS:
      Fifty-five premenopausal women with dermoid cysts. Intervention. Patients were
      randomly assigned to removal of dermoid cysts from the abdominal cavity with or
      without an endobag through a 10- to 12-mm cannula sleeve. MEASUREMENTS AND MAIN
      RESULTS: We assessed surgical time, spillage, complications, length of
      hospitalization, recurrences, and pregnancies. In the 55 women, 58 dermoid cysts
      (mean diameter 5.6 +/- 2.03 cm) were enucleated and removed at operative
      laparoscopy through a 10- to 12-mm cannula sleeve without intraoperative or
      postoperative complications. Mean operating time was 73 minutes. When cysts were
      removed with an endobag, operating time was significantly reduced over removal
      without the endobag (63 vs 81 min, p <0.05). Obvious spillage of endocystic
      contents occurred in 13 (43.3%) patients in group A but in only 1 patient in
      group B because the bag ruptured (p <0.05). No signs or symptoms of peritonitis
      were observed in women with evident cystic spillage or in those in group A in
      whom spillage was possible. Average postoperative hospital stay was 1.7 days and
      did not differ between groups. Among 20 infertile women, 9 (45%) experienced
      spontaneous pregnancy within a year, with no differences between groups.
      Echographic follow-up did not reveal cyst recurrence. CONCLUSIONS: Laparoscopic
      conservative cystectomy of dermoid cysts in premenopausal women is safe and
      effective and appears to be a valuable alternative to laparotomy. Removing cysts
      in an endobag significantly reduced both operating time and spillage. However,
      controlled intraperitoneal spillage of cyst contents does not increase
      postoperative morbidity as long as the peritoneal cavity is thoroughly washed.

PMID- 9564066
TI  - Hysteroscopic metroplasty.
AB  - STUDY OBJECTIVE: To evaluate 10 years' experience with hysteroscopic treatment of
      septate uterus in Italy. DESIGN: Multicenter retrospective study conducted from
      January 1988 to March 1997 (Canadian Task Force classification II-2). SETTING:
      Twelve Italian centers for minimally invasive therapy. PATIENTS: Women (total
      973) with hysteroscopically diagnosed septate uterus. INTERVENTIONS:
      Hysteroscopic metroplasty performed with scissors, resectoscope, or
      neodymium:yttrium-aluminum-garnet laser. MEASUREMENTS AND MAIN RESULTS: Data on
      indications for hysteroscopic metroplasty, details of patient management from
      pretreatment to follow-up, and pregnancy course and delivery were collected by
      questionnaire. Main indications were two or more abortions and primary
      infertility. Most procedures were performed with the resectoscope, followed by
      scissors and laser. Few minor complications occurred. Pregnancy rates were good.
      CONCLUSION: Hysteroscopy is safe and effective treatment of septate uterus in
      terms of both pregnancy rate and outcome.

PMID- 9564067
TI  - Improved laparoscopic operating techniques using a digital enhancement video
      system.
AB  - We conducted a prospective, randomized trial in a piglet model to assess the
      advantages of a digital enhancement video system during difficult endoscopic
      procedures. Laparoscopic pelvic lymphadenectomy was performed with either
      conventional two-dimensional or digitally enhanced videoendoscopy. With equal
      amounts of extirpated lymph nodes, the operations performed with digitally
      enhanced videoendoscopy were significantly shorter (left lymphadenectomy p =
      0.0001, right lymphadenectomy p = 0.001), had less blood loss and fewer false
      movements, and were associated with no complications, compared with those
      performed with a two-dimensional videosystem. Thus the accuracy of difficult
      laparoscopic techniques can be improved by three-dimensional visual perception.

PMID- 9564068
TI  - Laparoscopic colposuspension with a transvaginal illuminator.
AB  - A series of 63 women with anatomic stress urinary incontinence were treated at
      two institutions by laparoscopic urethrovesical suspension with vaginal
      transillumination of the paraurethral endopelvic fascia to facilitate
      laparoscopic dissection and ligature carrier and suture needle placement. In no
      case did illumination-assisted suture placement require suture removal or
      replacement for inadequate or traumatic placement within the bladder, or was it
      associated with hemorrhage. At a minimum of 2 years' follow-up, there were six
      treatment failures. The reusable illuminator enhances visual contrast between the
      pelvic floor and bladder neck for laparoscopic dissection and paraurethral needle
      placement. It also provides an effective backstop to the needle, eliminates
      needle injuries to operators' fingers during suturing, stabilizes the endopelvic
      fascia during dissection, and increases visual contrast between the bladder neck
      and adjacent endopelvic fascia.

PMID- 9564069
TI  - Laparoscopic cannula cone with means for cannula stabilization and wound closure.
AB  - A reusable cone suitable for use with existing laparoscopy cannulas was designed
      to provide means for sealing and stabilizing the operative site throughout the
      procedure, and for repairing the surgical site after the surgery is completed.
      The device consists of a moveable laparoscopic cannula cone fitted with suture
      holders. The cone contains tunnels terminating at its distal end that serve as
      passages for sutures loaded on a special needle to traverse the abdominal wall.
      When sutures are pulled into suture holders they stabilize the cannula and seal
      the puncture site. When sutures are tied at the end of the procedure, they
      achieve full-thickness closure of the operative site. The laparoscopic cannula
      cone stabilizes the cannula on the abdominal wall, maintains an air-tight seal,
      controls potential hemorrhage from the cannula puncture site, and achieves
      satisfactory closure of the surgical defect. Preliminary experience with the
      instrument and method has been most satisfactory.

PMID- 9564070
TI  - A new technique and system for simplifying total laparoscopic hysterectomy.
AB  - Because total laparoscopic hysterectomy (TLH) is technically challenging,
      laparoscopic-assisted vaginal hysterectomy is often the operation of choice, even
      in patients in whom it may not be successful. To encourage greater performance of
      TLH, I developed a technique and instrumentation that should enable gynecologists
      to do the operation successfully more often. The system consists of a pneumo
      occluder and a cup, combined with a uterine manipulator. The cup, which is both
      visible and palpable, is placed over the cervix to delineate vaginal fornices,
      thus ensuring safe desiccation and avoiding ureteral dissection. Acceptable
      operating times allow TLH to be combined with other procedures, including
      excision of endometriosis, colposuspension, and enterocele repair.

PMID- 9564071
TI  - Establishment of primary port without insertion of a sharp trocar.
AB  - A new method allows a primary laparoscopic port to be established without
      inserting a Veress needle or sharp cannula. In this prospective case series of
      348 consecutive healthy women undergoing elective laparoscopic sterilization, the
      laparoscope was complemented with an access cannula that enabled the surgeon to
      guide it directly into the abdominal cavity.

PMID- 9564072
TI  - A trocarless, reusable, visual-access cannula for safer laparoscopy; an update.
AB  - A new instrument for laparoscopic access consists of a trocarless, reusable,
      visual-access cannula with an external thread that ends in a blunt tip. The
      device has no sharp ends or moving parts. The cannula does not transect but
      radially stretches and elevates vessels, fascia, and muscle fibers, preserving
      the fascia's natural gridiron shutter mechanism at the access site. The outer
      thread stabilizes the cannula, and no fascial suture is necessary. In a
      prospective clinical trial between 1994 and 1997, the instrument was used in 203
      patients requiring 234 access ports for diagnostic and operative laparoscopies.
      No device-related complications or failed attempts were recorded. The cannula
      caused less tissue trauma at access sites, and may decrease the frequency of
      hernias and postoperative access site pain.

PMID- 9564073
TI  - Laparoscopic supracervical hysterectomy with a new disposable morcellator.
AB  - Laparoscopic supracervical hysterectomy (LSH) can be performed more easily with a
      powered morcellator for removal of the uterus. Available laparoscopic
      morcellators are expensive and may be difficult to use, but a new, powered,
      disposable instrument was developed (Diva; FemRx, Sunnyvale, CA) to morcellate
      the entire uterus for easy removal through a 15-mm cannula. Twelve consecutive
      women for whom subtotal hysterectomy was indicated underwent LSH by standard
      laparoscopic protocol and were monitored postoperatively for a minimum of 1
      month. In the current trend of "less is more," LSH is an emerging option for less
      extensive hysterectomies and can be made more cost and time effective with a
      single-use powered morcellator.

PMID- 9564074
TI  - Transvaginal needle suspension with LeFort colpocleisis for stress incontinence
      and advanced uterovaginal prolapse in a high-risk patient.
AB  - Surgical therapy in high-risk patients with advanced symptomatic pelvic floor
      defects sometimes mandates a compromise in the extent of proposed and desired
      repairs in favor of procedures that can be performed more rapidly. An 80-year-old
      woman with disabling genuine stress urinary incontinence and stage IV
      uterovaginal prolapse who was unable to retain a pessary was at high surgical
      risk due to ischemic heart disease. Uterovaginal prolapse was treated by LeFort
      partial colpocleisis, and stress urinary incontinence by transvaginal needle
      suspension with symptomatic cure and without significant perioperative morbidity.
      Operating time was 29 minutes and estimated blood loss was 50 ml. The patient was
      discharged on the second postoperative day with adequate spontaneous voiding and
      without urinary retention. A combination of partial colpocleisis with
      transvaginal needle suspension worked well in this case and may represent an
      effective and rapid surgical option for similar women.

PMID- 9564075
TI  - Uterine leiomyoma metastasis as a first sign of breast cancer.
AB  - Uterine metastases from extragenital cancer are rarely reported in the
      literature. More frequently, the female genital tract is involved by direct
      extension from an adjacent pelvic organ. A 37-year-old woman had a myoma of the
      uterine wall and hypermenorrhea. The mass was laparoscopically enucleated, and
      frozen section examination was performed because it was macroscopically
      suspicious for sarcomatoid degeneration. The final diagnosis was metastatic
      carcinoma in the uterus of probable breast origin.

PMID- 9564076
TI  - Gloves--personal protection or heath hazard? (What every dental nurse should
      know).

PMID- 9564078
TI  - Special needs dental nursing in the South West.

PMID- 9564077
TI  - "My" special needs dental nurse.

PMID- 9564079
TI  - Provision of general anaesthesia for the community dental service within a
      district general hospital day surgery unit.

PMID- 9564080
TI  - Dentistry from the back of a covered wagon.

PMID- 9564081
TI  - Lasers in dentistry.

PMID- 9564082
TI  - A method for introducing the concepts of chaos theory to medical students.
AB  - Chaos theory is beginning to find applications in the field of medicine. The
      theory of chaos should be introduced to students to help them as they make the
      transition from learning the scientific literature to actually applying this
      newly acquired knowledge in clinical situations. Chaos theory will give the
      students a powerful conceptual framework from which they can better understand
      the limits of predictability in clinical situations. Failure to understand the
      limits of predictability in chaotic natural systems will invariably lead to
      frustration in both patients and physicians.

PMID- 9564083
TI  - Decision-making through dialogue: reconfiguring autonomy in genetic counseling.
AB  - Nondirective genetic counseling developed as a means of promoting informed and
      independent decision-making. To the extent that it minimizes risks of coercion,
      this counseling approach effectively respects client autonomy. However, it also
      permits clients to make partially informed, poorly reasoned or ethically
      questionable choices, and denies counselors a means of demonstrating
      accountability for the use of their services. These practical and ethical
      tensions result from an excessive focus on noncoercion while neglecting the
      contribution of adequate information and deliberative competence to autonomous
      decision-making. A counseling approach that emphasizes the role of deliberation
      may more reliably produce thoroughly reasoned decisions. In such an approach,
      characterized by dialogue, counselors are responsible for ensuring that decisions
      are fully informed and carefully deliberated. Counseling remains nonprescriptive,
      but in the course of discussion counselors may introduce unsolicited information
      and/or challenge what they believe are questionable choices. By this means
      clients can be better assured that the decisions they make are fully considered,
      while counselors demonstrate a limited degree of professional accountability.

PMID- 9564084
TI  - On sentiment, caring and anencephalics: a response to Sytsma.

PMID- 9564085
TI  - Some philosophies can console: an old but forgotten message.
AB  - Thesis: Since Socrates, western philosophy has been concerned with the study of
      humankind, with a strong emphasis on how we ought to live and why. Philosophy, in
      its multiple forms and expressions, has enabled many to pursue their lives with
      greater depth, richness, and variety; yet it can also act as a therapeutic method
      for the achievement of a healthier life. Asking and answering philosophical
      questions such as 'How best ought I live?', 'What is the meaning of my life in
      relation to the whole?', 'Why should I live?', 'What constitutes a healthy life?'
      can act as therapeutic entryways, not only within the parameters of one's own
      mind or in a university classroom, but also within a health care/therapy context.
      Philosophy, both as subject and method, is a powerful, largely unrecognized,
      therapeutic instrument for social medicine, an instrument whose application in
      various health care settings could benefit those--patient and staff--in need of
      consolation and support when they need it most.

PMID- 9564086
TI  - Distanced perspectives: AIDS, anencephaly, and AHP.
AB  - US court decisions guaranteeing life-sustaining care to anencephalic infants have
      been viewed with disfavor, and sometimes disbelief, by some ethicists who do not
      believe in the necessity of life-sustaining support for those without cognitive
      abilities or an independently sustainable future. The distance between these two
      views--one legal and inclusive, the other medical and specific--seems
      unbridgeable. This paper reports on a program using multicriterion decision
      making to define and describe persons in a way which both acknowledges the
      differences perceived by many as well as those commonalities insisted on in U.S.
      court decisions. It does this through application of the Analytic Hierarchy
      Process to a hierarchy of "humanness" criteria, and secondarily through reference
      to that concept's subset, personhood.

PMID- 9564087
TI  - Competing conceptions of diagnostic reasoning--is there a way out?
AB  - Diagnostic errors are more frequently a result of the clinician's failure to
      combine medical knowledge adequately than of data inaccuracy. Diagnostic
      reasoning studies are valuable to understand and improve diagnostic reasoning.
      However, most diagnostic reasoning studies are characterized by some limitations
      which make these studies seem more simple than diagnostic reasoning in real life
      situations actually is. These limitations are connected both to the failure to
      acknowledge components of knowledge used in clinical practice as well as to
      acknowledge the physician-patient relationship's influence on clinical knowledge
      and on the reasoning process itself. In addition the modes of reasoning described
      in these studies frequently is oversimplified. In this paper three simplistic and
      competing models of diagnostic reasoning are analyzed and criticized, followed by
      an evaluation of two alternative models proposing a combined view.

PMID- 9564088
TI  - Nihilism, relativism, and Engelhardt.
AB  - This paper is a critical analysis of Tristram Engelhardt's attempts to avoid
      unrestricted nihilism and relativism. The focus of attention is his recent book,
      The Foundations of Bioethics (Oxford University Press, 1996). No substantive or
      "content-full" bioethics (e.g., that of Roman Catholicism or the Samurai) has an
      intersubjectively verifiable and universally binding foundation, Engelhardt
      thinks, for unaided secular reason cannot show that any particular substantive
      morality (or moral code) is correct. He thus seems to be committed to either
      nihilism or relativism. The first is the view that there is not even one true or
      valid moral code, and the second is the view that there is a plurality of true or
      valid moral codes. However, Engelhardt rejects both nihilism and relativism, at
      least in unrestricted form. Strictly speaking, he himself is a universalist,
      someone who believes that there is a single true moral code. Two argumentative
      strategies are employed by him to fend off unconstrained nihilism and relativism.
      The first argues that although all attempts to establish a content-full morality
      on the basis of secular reason fail, secular reason can still establish a content
      less, purely procedural morality. Although not content-full and incapable of
      providing positive direction in life, much less a meaning of life, such a
      morality does limit the range of relativism and nihilism. The second argues that
      there is a single true, content-full morality. Grace and revelation, however, are
      needed to make it available to us; secular reason alone is not up to the task.
      This second line of argument is not pursued in The Foundations at any length, but
      it does crop up at times, and if it is sound, nihilism and relativism can be much
      more thoroughly routed than the first line of argument has it. Engelhardt's
      position and argumentative strategies are exposed at length and accorded a
      detailed critical examination. In the end, it is concluded that neither strategy
      will do, and that Engelhardt is probably committed to some form of relativism.

PMID- 9564089
TI  - Nordenfelt's theory of disability.
AB  - This paper is an attempt to provide a critical evaluation of the theory of
      disability put forward by Lennart Nordenfelt. The paper is in five sections. The
      first sets out the main elements of Nordenfelt's theory. The second section
      elaborates the theory further, identifies a tension in the theory, and three
      kinds of problems for it. The tension derives from Nordenfelt's attempt to
      respect two important but conflicting constraints on a theory of health. The
      problems derive from characterisation of the goals of persons; the difficulty
      which Nordenfelt has in respecting the plausible view that there is a distinction
      between illness and disability; and the presence in the theory of other strongly
      counterintuitive implications. In section three a defence of Nordenfelt is
      attempted from within the resources available within his own theory. This defence
      seeks to exploit his distinctions between a person who is ill and one who is
      'generally disabled' and that between first- and second-order disabilities.
      However, it is concluded that there are insufficient resources within
      Nordenfelt's theory to fend off the criticisms developed in section two. The
      fourth section of the paper attempts a defence of Nordenfelt. It is claimed that
      introduction of the concept of capacity helps to explain differences between
      problem cases in the theory. Finally, it is shown that at least two important
      constraints on any theory of disability emerge from the preceding discussion.

PMID- 9564090
TI  - What bioethics needs to learn about families.

PMID- 9564091
TI  - Ethics and imagination. Implications of cognitive semantics for medical ethics.
AB  - Cognitive semantics has made important empirical findings about human
      conceptualization. In this paper some findings concerning moral concepts are
      analyzed and their implications for medical ethics discussed. The key idea is
      that morality has to do with metaphors and imagination rather than with well
      defined concepts and deduction. It is argued that normative medical ethics to be
      psychologically realistic should take these findings seriously. This means that
      an "imaginative casuistry" is to be preferred compared to principlism and to
      other forms of casuistry. Furthermore, the metaphorical character of central
      principles in medical ethics such as autonomy, utility, justice, and integrity is
      indicated. Such principles are interpreted as rules of thumb summarizing the
      collective wisdom concerning prototype cases.

PMID- 9564092
TI  - The crumbling foundations of medical ethics.

PMID- 9564093
TI  - On being unprincipled.

PMID- 9564094
TI  - Fraud and abuse. Federal civil health care litigation and settlement.

PMID- 9564095
TI  - Advance directives. The next generation.

PMID- 9564096
TI  - The duty to care--the right to refuse. Changing roles of patients and physicians
      in end-of-life decision making.

PMID- 9564097
TI  - Higher penalties for failing to pay child support. A look at medical license
      revocation.

PMID- 9564099
TI  - A case of a malignant mixed tumor in the vagina.
AB  - Malignant mixed tumors in the vagina are extremely rare. We experienced a case of
      a malignant mixed tumor (synovioid variant). Surgical treatment was performed,
      followed by 3 courses of chemotherapy. Up to the present time, 4 years after the
      first treatment, no signs of recurrence have been observed.

PMID- 9564098
TI  - Efficacy of intracervicovaginal misoprostol in second-trimester pregnancy
      termination: a comparison between live and dead fetuses.
AB  - OBJECTIVE: To study the complications and compare the success rate and abortion
      time between the live and the dead fetuses in second-trimester pregnancy
      termination with intracervicovaginal misoprostol. DESIGN: A prospective
      comparative study. SUBJECTS AND METHODS: A total of 89 pregnant women between 14
      and 28 weeks of gestation with obstetric, medical, or genetic reasons for
      termination of pregnancy were recruited to receive 200 micrograms misoprostol
      inserted intracervicovaginally every 12 hours. RESULTS: The rates of successful
      abortions within 12, 24 and 48 hours in live fetuses were 15.1%, 54.7% and 92.5%,
      respectively, while in dead fetuses were 50.0%, 83.3% and 97.2%, respectively.
      The success rates within 12 and 24 hours in live-fetus group were significantly
      lower than those of the dead-fetus group 9p = 0.0009 and p = 0.01, respectively).
      The mean abortion time of the live-fetus group (27.1 hours) was significantly
      more than that of the dead-fetus group (15 hours, p = 0.001). No serious
      complications occurred in terms of hemorrhage, febrile morbidity diarrhea, nausea
      and vomiting. CONCLUSIONS: Intracervicovaginal misoprostol is an effective and
      safe method for second-trimester pregnancy termination. The success rate is
      higher and the abortion time is less in dead-fetus pregnancy than those in the
      live-fetus pregnancy.

PMID- 9564100
TI  - Malaysian antenatal risk coding and the outcome of pregnancy.
AB  - OBJECTIVE: Measure the effectiveness of the colour coding system in Malaysia for
      the prediction of risk in pregnancy. METHOD: Cohort study of records and
      interviews of 253/279 women examined at first antenatal visit. RESULTS: Nurses'
      final coding showed poor concordance with guidelines; recoding produced a
      predictive value of high risk of 48%; 25% of those with low risk had 50% of
      complications. Complication rates were moderate and intervention rates low. The
      mothers had little appreciation of risk and preferred home delivery. Home
      deliveries gave excellent results except for the 17% requiring transfer to
      hospital during labour or delivery. CONCLUSION: The coding system is ineffective
      with Malaysia's relatively low reproductive risk. Women require more personalised
      counseling about risk to make appropriate choices. Better results depend on
      simpler but consistent selection for hospital delivery using reproductive
      history, combined with better communication and transport systems for home
      deliveries and a reorientation within hospitals to rapid emergency care.

PMID- 9564101
TI  - The usefulness of screening for chlamydial trachomatis infection with cervical
      mucus leukocyte esterase.
AB  - OBJECTIVE: To evaluate the ability of leukocyte esterase dipstick test (LET)
      performed in cervical mucus to predict direct immunofluorescent (DIF)-verified
      Chlamydia trachomatis (Ct) cervical infection. METHOD: Eighty women with
      inflammatory cervico-vaginal smear were submitted to both an endocervical smear,
      to verify Ct cervicitis by DIF technique; and a cervical mucus sample to perform
      LET. Results of LET and DIF were matched. RESULTS: Among 30 Chlamydial positive
      subjects, cervical mucus esterase test was positive in 28 (93.3%); while among 50
      Chlamydial negative controls, esterase test was negative in 43 subject (86%). The
      sensitivity, specificity, positive and negative predictive values for LET were
      93.3%, 86%, 80% and 95% respectively. CONCLUSION: Cervical mucus LET is a simple,
      cost effective screening test, with promising accuracy, for Ct cervical infection
      among women with inflammatory cervico-vaginal smears.

PMID- 9564102
TI  - Early invasive adenocarcinoma of the fallopian tube: a case report and review of
      the literature.
AB  - We present an early invasive adenocarcinoma of the fallopian tube, which was
      incidentally found in a 45-year-old woman undergoing a laparotomy for uterine
      myoma. Histological examination of the hydropic tubes revealed widespread
      endosalpingeal hyperplasia without atypia in both tubes. In addition, the left
      tube contained 3 scattered lesions of carcinoma in situ, one of which was
      accompanied by a microfocus of definite stromal invasion confined within the
      endosalpingeal mucosa. Such a case seems extremely rare, and it might represent
      the histological appearance of an early invasive feature of tubal carcinoma. We
      reviewed previously reported cases of in situ and/or early invasive carcinomas of
      the fallopian tube with respect to the pathological diagnosis and histogenesis of
      primary tubal adenocarcinomas.

PMID- 9564103
TI  - Magnetic resonance imaging of fetal autosomal recessive polycystic kidney
      disease.
AB  - We present a case of fetal autosomal recessive polycystic kidney disease (ARPKD)
      at 34 weeks of gestation, diagnosed by magnetic resonance imaging (MRI). MRI
      demonstrated enlarged fetal kidneys that were low signal intensity on T1-weighted
      images and high signal intensity on T2-weighted images. These MRI findings
      suggested a high water content in the renal parenchyma, consistent with the
      innumerable, tiny renal cysts present in ARPKD.

PMID- 9564104
TI  - A case of concurrent uterine cervical adenocarcinoma and renal-cell carcinoma,
      and subsequent vaginal metastasis from the renal-cell carcinoma.
AB  - We report a case of concurrent uterine cervical adenocarcinoma and renal-cell
      carcinoma and a subsequent vaginal metastasis from the renal-cell carcinoma. The
      renal-cell carcinoma, which was located in the upper pole of the right kidney,
      was detected incidentally by preoperative CT scanning. We simultaneously
      performed in a timely manner radical hysterectomy, pelvic and paraaortic
      lymphadenectomies, and a right nephrectomy. Subsequently, however, the patient
      suffered from vaginal metastasis arising from the renal-cell carcinoma. As a
      result of this case, we emphasize the importance of making a thorough
      preoperative assessment prior to performance any definitive surgery for a
      gynecologic malignancy.

PMID- 9564105
TI  - Ovarian pregnancy associated with microscopic decidualized endometriosis of the
      ovary: report of a case.
AB  - A case of ovarian pregnancy associated with microscopic endometriosis is
      described. The case satisfied Spiegelberg's four criteria. The associated
      endometriotic lesion histologically showed prominent decidual change.

PMID- 9564106
TI  - The relationship between maternity blues and thyroid dysfunction.
AB  - OBJECTIVE: To investigate whether there is evidence of thyroid dysfunction in
      women with maternity blues. METHODS: Twenty women with maternity blues and 20 age
      matched normal controls were enrolled in our study. The serum levels of 6 kinds
      of thyroid hormones, cortisol, and prolactin (PRL) of the 2 groups were compared,
      and obstetric variables were recorded for each subject. In addition, significant
      variables correlating with the development of maternity blues were determined by
      stepwise regression analysis. RESULTS: The serum-free triiodothyronine (FT3)
      level at 5 days puerperium was lower in the maternity blues group (p < 0.05) than
      in the control group. In the maternity blues group, the FT3 level at 5 days
      puerperium was lower than that at 37 weeks of pregnancy and at 1 month puerperium
      (p < 0.05). The reverse T3 levels and TSH levels at 5 days postpartum were higher
      in women with maternity blues than among the controls (p < 0.05). The proportion
      of primiparous women was higher in the maternity blues group (p < 0.01). Stepwise
      regression analysis revealed that the low FT3 level and primiparity were
      significantly correlated with the development of maternity blues (R2 = 0.281, p <
      0.001). CONCLUSION: Thyroid dysfunction might be associated with the development
      of maternity blues.

PMID- 9564107
TI  - Vertical transmission of hepatitis C virus: risk factors and infantile prognosis.
AB  - OBJECTIVES: To clarify the incidence and risk factors of the vertical
      transmission of hepatitis C virus (HCV) and to determine the prognosis of the
      carrier infants. METHODS: At our hospital, 1,941 non-pathological (non-HIV
      carriers) Japanese pregnant women were screened for anti-HCV antibodies. Sera of
      the antibody-positive women were examined by the reverse transcription polymerase
      chain reaction (RT-PCR) method, and the positive women and their infants were
      followed by testing HCV-related markers. RESULTS: The HCV carrier rate among the
      pregnant women was 3.5% (68/1,941). Four among the 65 infants (6.2%) who were
      successfully followed for more than 6 months developed the HCV carrier-state. Of
      all the risk factors examined, only the elevation (> or = 110 IU/l) of maternal
      serum alanine aminotransferase (ALT) was found to be significant for HCV vertical
      transmission. Seventy-five and 50% of the carrier infants manifested chemical
      hepatitis and seroconverted to an HCV-RNA-negative status, respectively, during
      the follow-up period. CONCLUSIONS: The frequency of HCV vertical transmission was
      6.2%. Half of the carrier infants became seronegative for HCV-RNA. HCV vertical
      transmission was significantly affected by the maternal serum ALT level prior to
      delivery.

PMID- 9564108
TI  - Changes in purine metabolism and production of oxygen free radicals by
      intermittent partial umbilical cord occlusion in chronically instrumented fetal
      lambs.
AB  - OBJECTIVE: Undetected umbilical-cord compression has been suggested to be
      implicated in unexplained fetal brain damage. We tested the hypothesis that the
      generation of oxygen-free radicals (OFRs) during intermittent partial umbilical
      cord occlusion might play a causal role in antenatal CNS injury. METHODS: Using 7
      established chronically instrumented fetal lambs, intermittent partial occlusion
      of the umbilical circulation was produced according to the method of Clapp et al.
      for 1 of every 3 minutes for 2 hours. A microdialysis probe was implanted in the
      fetal brain white matter. Normal saline was infused, and the perfusate obtained
      at 2 micrograms/ min. Hypoxanthine (HX), xanthine (XA), and inosine-5
      monophosphate (IMP) concentrations in the perfusate and blood samples obtained
      from fetal jugular veins were assayed by HPLC. Concurrently, the perfusate, which
      contained superoxide produced in the brain, when mixed with cypridina luciferin
      analogue extracorporally, caused chemiluminescence that in 4 cases was measured
      by a highly sensitive electronic fluorescence detector. RESULTS: (1) HX, XA, and
      IMP concentrations in the blood and perfusate were higher than in the control
      during the intermittent partial occlusion of the umbilical circulation period and
      returned to control levels during the recovery period. (2) The residual
      chemiluminescence of perfusate revealed that the intermittent partial occlusion
      of the umbilical circulation level was about 100% higher than the control level,
      and during the recovery period the level returned to the control level. (3) The
      chemiluminescence during the intermittent partial occlusion of the umbilical
      circulation period was inhibited by infusion through the fetal jugular vein of 1
      micron polyethylene glycol conjugated superoxide dismutase. CONCLUSION: During
      the intermittent partial occlusion of the umbilical circulation period the fetal
      brain tissue releases a large amount of OFRs, and a portion of these might be
      synthesized by the increased conversion of HX to XA. This phenomenon might play
      an important role in the etiology of fetal brain injury.

PMID- 9564109
TI  - Elevated fetal fibronectin in midtrimester amniotic fluid is involved with the
      onset of preeclampsia.
AB  - OBJECTIVE: To examine early midtrimester amniotic fluid for its significance in
      pregnancy outcomes, especially with connection to the pathogenesis of
      preeclampsia. METHODS: A prospective, nested, case-control study was conducted.
      Fetal fibronectin in early midtrimester (16-20 weeks gestation) amniotic fluid
      was measured by EIA method. Results were compared by their pregnancy outcomes.
      RESULTS: Amniotic fluid levels of fetal fibronectin were significantly higher in
      the group subsequently developing severe preeclampsia (106.8 +/- 13.2
      micrograms/ml, mean +/- SD, n = 12) compared with matched controls (66.7 +/- 7.1
      micrograms/ml, n = 12) (p < 0.05). CONCLUSION: High levels of fetal fibronectin
      were found in the amniotic fluid of women subsequently developing severe
      preeclampsia before any symptom appear. Involvement of extracellular injury or
      cellular hyperactivity in the midtrimester placental site with the onset of
      preeclampsia is suggested.

PMID- 9564110
TI  - A prospective randomized control study to compare the effect of serum and a
      commercial serum substitute (Plasmanate) on the outcome of assisted reproduction
      program.
AB  - OBJECTIVES: To compare the effect of supplementation of serum and Plasmanate, a
      commercial serum substitute, to culture medium on the IVF outcome. METHODS: One
      hundred eighty-nine subfertile couples were prospective randomized into the serum
      and the Plasmanate group during their IVF treatment. In vitro experiment was also
      performed to determine the fraction of Plasmanate that might affect embryo
      development. RESULTS: The pregnancy rate were similar in both groups. The
      fertilization rate, the number of gestational sacs and good quality spare embryos
      suitable for cryopreservation were higher in the serum group than the Plasmanate
      group. However, these differences did not reach statistical significance.
      Significantly more embryos in the former cleaved to more than 4 cells at the time
      of transfer than the latter (p < 0.05). Ultrafiltration study showed that this
      inhibitory effect resided in the low molecular weight fraction (< 30-KD) of
      Plasmanate. CONCLUSION: Serum is slightly better than Plasmanate as a protein
      supplement. However, Plasmanate may still be used for short term embryo culture
      in assisted reproduction.

PMID- 9564111
TI  - Re: Opioid-induced myoclonus and seizures.

PMID- 9564112
TI  - Rectal omeprazole in the treatment of reflux pain in esophageal cancer.

PMID- 9564113
TI  - Re: Inappropriate use of the epidural route.

PMID- 9564114
TI  - Re: Management of diabetes in advanced cancer: urine sugar tests.

PMID- 9564115
TI  - Can professionals improve their assessments?

PMID- 9564116
TI  - Quality-of-life evaluation: when do terminal cancer patients and health-care
      providers agree?
AB  - A multicenter study involving six palliative care units in Italy was carried out
      on 159 terminal cancer patients seen at home or in hospital. The physician or the
      nurse completed independently from the patient the Therapy Impact Questionnaire
      (TIQ), a questionnaire devised for quality-of-life evaluation in terminal cancer
      patients. The patient's assessment was used as the valid reference measurement to
      compare with the health-care workers' evaluation to assess the validity of the
      latter. The results showed that percentages of agreement were higher for physical
      than for psychological and cognitive symptoms, and that there was a greater
      agreement on the absence rather than on the presence of a problem. None of the
      characteristics of the patient nor of the proxy showed any statistically
      significant relationship with the two disagreement indexes. The results suggest
      that caution is needed in the use of health-care workers as alternative sources
      of information regarding patients' quality of life.

PMID- 9564117
TI  - Fatigue in ambulatory AIDS patients.
AB  - Although preliminary reports indicate that fatigue is a common symptom of human
      immunodeficiency virus (HIV) disease, little empirical research has focused on
      its prevalence or characteristics among patients with acquired immunodeficiency
      syndrome (AIDS). We assessed the frequency of fatigue and its medical and
      psychological correlates, in a cross-sectional survey of ambulatory AIDS
      patients. Ambulatory patients with AIDS who participated in a study of quality
      life (N = 427) were classified into fatigue/no fatigue groups based on their
      responses to fatigue items on the Memorial Symptom Assessment Scale (MSAS) and
      the AIDS physical symptom checklist. Self-report inventories were also
      administered to assess psychological distress, depressive symptoms, and overall
      quality of life. Medical information was elicited through clinical interview and
      review of medical chart. Fifty-four percent of the patients endorsed both of the
      fatigue items from the MSAS and the AIDS physical symptom checklists, and were
      classified as having fatigue. Women were significantly more likely to report
      fatigue than men (chi square = 5.28, df = 1, P < 0.03), and patients reporting
      homosexual contact as their transmission risk factor were significantly less
      likely to report fatigue than were patients reporting injection drug use or
      heterosexual contact (chi square = 5.13, df = 2, P < 0.03). The presence of
      fatigue was significantly associated with the number of current AIDS-related
      physical symptoms [t(425) = 8.00, P < 0.0001], current treatment for HIV-related
      medical disorders (chi square = 12.51, df = 1, P < 0.0001), anemia [t(174) = 
      2.35, P < 0.02], and pain (chi square = 36.36, df = 1 P < 0.0001). Patients with
      fatigue also had significantly poorer physical functioning ability [Karnofsky:
      t(422) = -6.27, P < 0.0001], as well as greater degree of overall psychological
      distress and lower quality of life [F(5,418) = 23.79, P < 0.0001], as measured by
      the Brief Symptom Inventory, Beck Depression Inventory, Beck Hopelessness Scale,
      Functional Living Inventory for Cancer (modified for AIDS), and the MSAS
      Psychological Distress Subscale. Fatigue is a common symptom in ambulatory AIDS
      patients and is associated with significant physical and psychological morbidity.

PMID- 9564118
TI  - Long-term treatment of cancer pain with transdermal fentanyl.
AB  - The long-term therapy of 51 patients using transdermal fentanyl was evaluated.
      The transdermal therapy was performed for 158 days (range, 15-855 days). The need
      for increasing dosages of transdermal fentanyl was caused by the progression of
      the underlying cancer disease (mean initial dose, 69.5 micrograms fentanyl/hr;
      mean final dose, 167.7 micrograms fentanyl/hr). The transdermal system was
      changed every third day. Application intervals had to be shortened in 23.5% of
      the patients. Pain reduction was good throughout the study. Severe side effects
      did not occur. Constipation and the need for laxatives occurred less frequently
      than with previously administered oral morphine. Skin tolerance of the
      transdermal system was good. The treatment of cancer pain with transdermal
      fentanyl can be performed as a long-term therapy and result in good pain relief.
      Considering its specific pharmacokinetic properties, it is an alternative
      medication on step III of the World Health Organization's guidelines for cancer
      pain management.

PMID- 9564119
TI  - Comparison of tropisetron and chlorpromazine combinations in the control of
      nausea and vomiting of patients with advanced cancer.
AB  - The single-institution, prospective, randomized trial was performed to evaluate
      the efficacy of tropisetron and chlorpromazine in the management of nausea and
      vomiting of terminal cancer patients. Patients had no recent chemotherapy or
      radiotherapy, and emesis was not due to bowel obstruction, electrolytic or
      metabolic disturbances, drug intake, or intracranial disease. One hundred and
      sixty patients randomly received either (a) chlorpromazine (CLO) (50 mg/day) plus
      dexamethasone (DEX) (2 mg/day), (b) chlorpromazine (25 mg/day) plus tropisetron
      (TRO) (5 mg/day), (c) chlorpromazine (25 mg/day plus tropisetron (5 mg/day) plus
      dexamethasone (2 mg/day), or (d) tropisetron (TRO) (5 mg/day). Patients were
      monitored from day 1 to day 15. No nausea or vomiting was defined as "total"
      control. On day 15, total vomiting control was achieved in 33.3% of the patients
      receiving CLO + DEX, 84.6% of the patients receiving CLO + TRO, 92.5% of the
      patients receiving CLO + TRO + DEX, and 78.9% of the patients receiving TRO.
      Total control of nausea was achieved in 18.0% of the patients receiving CLO +
      DEX, 74.4% of the patients receiving (CLO + TRO), 85.0% of the patients receiving
      CLO + TRO + DEX, and 65.8% of the patients receiving TRO. Tropisetron-containing
      combinations produced significant control of nausea and vomiting from the third
      day onward. All antiemetic drugs were well tolerated. These data suggest that
      tropisetron-containing combinations or tropisetron as a single agent are much
      more effective in the control of emesis in patients with advanced cancer than the
      conventional antiemetic combination of chlorpromazine plus dexamethasone.
      Tropisetron is well tolerated and may be the best choice for controlling
      persistent nausea and vomiting in terminal cancer patients.

PMID- 9564120
TI  - Outcome of chronic opioid therapy for non-cancer pain.
AB  - Potential iatrogenic mood and cognitive declines associated with long-acting
      opioid therapy were examined in 19 patients receiving long-acting oral opioid
      medications and compared to ten patients receiving usual care. Pain, mood, and
      cognitive function were measured before and after achieving stable doses. In
      addition to reducing pain, long-acting opioid medication reduced anxiety and
      hostility. No declines in cognitive function were associated with the long-acting
      opioid medications, and the group receiving long-acting opioid medications showed
      significant improvement on a measure of psychomotor speed and sustained
      attention. Both patient groups reported significant reductions in perceived
      impairment in daily activities due to pain. Treatment responders taking long
      acting opioid medications (63%) were taking a significantly lower dose at follow
      up than the treatment non-responder group. These findings suggest that long
      acting opioid medications can improve mood and do not impair cognitive
      functioning in patients with chronic non-cancer pain.

PMID- 9564121
TI  - Integration of palliative medicine at the Medical College of Wisconsin 1990-1996.
AB  - Palliative medicine is an emerging world-wide discipline. This article describes
      efforts at the Medical College of Wisconsin (MCW) to develop programs to enhance
      palliative medicine education and clinical care. New courses, seminars and
      clinical programs have been developed. Education and clinical care activities
      since 1990 have included a required course for second-year medical students,
      clinical electives for third- and fourth-year medical students, a clinical
      palliative care consultation service, a palliative care seminar series designed
      for housestaff, and a nurse preceptorship program. Palliative medicine activities
      have included both the academic medical center and community health agencies. MCW
      has integrated palliative medicine into its academic environment so that trainees
      at all education levels now have opportunities for didactic and clinical end-of
      life care education.

PMID- 9564122
TI  - Change and continuity in the Journal of Pediatric Psychology.

PMID- 9564123
TI  - Relationship of parental psychological distress to consequences of chronic health
      conditions in children.
AB  - OBJECTIVE: To assess whether parents' self-reported psychological distress was
      related to consequences of chronic health conditions in their children as
      reflected by three domains: functional limitations, reliance on compensatory
      mechanisms, and service use above routine care. METHODS: We used telephone survey
      data on children's health and parents' psychiatric symptoms from an inner-city
      community sample (n = 380) and a population-based national sample (n =398).
      RESULTS: In the national sample, parents of children with functional limitations
      were more distressed than parents whose children experienced other types of
      condition consequences or none. In the inner-city sample, presence of a health
      condition was associated with greater parental distress, but there were no
      significant effects by consequence type. CONCLUSION: Research needs to determine
      if parents of children with functional limitations represent a high-risk group
      and to identify the factors associated with their elevated distress.

PMID- 9564124
TI  - Matching preparatory intervention to coping style: The effects on children's
      distress in the dental setting.
AB  - OBJECTIVE: Investigate the effects of matching preparatory interventions to
      patient's coping styles. METHODS: Participants were 61 children, with a
      restricted age range of 6 through 9 years old (mean age was 7.9 years), who
      underwent dental restoration. Participants were randomly assigned to an
      information intervention, a relaxation intervention, or a control condition. Play
      and parent-report of sensitization/repression were indices of coping style. The
      first hypothesis, that play would relate to sensitization/repression, was tested
      using Pearson correlations. The second hypothesis, that interventions that were
      congruent with patients' coping styles would be more effective than incongruent
      interventions, was tested using MANCOVAs. RESULTS: No relation was found between
      play and coping style. The "congruency hypothesis" was supported for self
      reported distress immediately following the intervention. On behavioral distress
      variables, the interaction between sensitization/repression and condition was
      contrary to the congruency hypothesis. CONCLUSIONS: Implications for future
      research and clinical intervention with pediatric populations were discussed.

PMID- 9564127
TI  - Why do boys engage in more risk taking than girls? The role of attributions,
      beliefs, and risk appraisals.
AB  - OBJECTIVE: Assessed for age and sex differences in school-age children's
      reporting of injury-risk behaviors, ratings of injury-risk in various play
      situations, attributions for injuries (self, other, bad luck), and beliefs about
      their vulnerability to injury in comparison to their peers (more, less,
      comparable vulnerability). METHODS: We used a structured interview and drawings
      that depicted children showing wary or confident facial expressions when engaged
      in injury-risk play activities. RESULTS: Children's reported risk taking could be
      predicted from their risk appraisals, beliefs about the likelihood of injury, and
      attributions of injuries to bad luck, and these factors resulted 80% correct
      assignment of cases by sex in a discriminant analysis. The wary affect display
      resulted in higher injury-risk ratings than the confident display, with this
      effect being greater for girls than boys. CONCLUSIONS: Cognitive-based factors
      differentiate boys from girls and contribute to sex differences in children's
      injury-risk behaviors.

PMID- 9564129
TI  - The role of the family system in HIV risk reduction: youths with hemophilia and
      HIV infection and their parents. Adolescent Hemophilia Behavioral Intervention
      Evaluation Project (HBIEP) Study Group.
AB  - OBJECTIVE: To examine the relationship between family communication and HIV risk
      reduction behaviors among a multisite sample of 125 male youths (ages 12-25) with
      hemophilia and HIV- infection, as well as their parents. METHODS: Participants
      completed self-report surveys assessing communication and attitudes regarding HIV
      risk reduction interventions; adolescents also provided data about their sexual
      behaviors. RESULTS: Adolescents with parents who discuss sexual issues were more
      likely to report HIV status disclosure to sexual partners. Most parents were
      supportive of HIV risk reduction interventions for their adolescents, but the
      youths themselves tended to endorse only interventions that offered opportunities
      for recreational activities and socialization with peers. CONCLUSIONS: Findings
      are discussed in terms of intervention implications and the need for family
      systems-based programs.

PMID- 9564128
TI  - Hemophilia growth and development study: relationships between
      neuropsychological, neurological, and MRI findings at baseline.
AB  - OBJECTIVE: To determine the effects of human immunodeficiency virus (HIV)
      infection on children's development by identifying neurological and environmental
      variables associated with neuropsychological measures of cognitive development in
      HIV-seronegative (HIV-) and HIV-seropositive (HIV+)children and adolescents with
      hemophilia. METHODS: Participants (N = 298; 60% HIV+) were males ages 7-19 years
      enrolled in the Hemophilia Growth and Development Study (HGDS). Least squares
      modeling was used to determine whether there was a difference at baseline in mean
      neuropsychological test scores by HIV status, age, and neurological baseline
      findings, adjusting for selected environmental and medical history variables.
      RESULTS: The participants were within age expectations for general intelligence.
      Variables associated with lowered neuropsychological performance included
      academic problems, coordination and/or gait abnormalities, parents' education,
      and previous head trauma. CONCLUSIONS: Hemophilia-related morbidity has a subtle
      adverse influence on cognitive performance. HIV infection was not associated with
      neuropsychological dysfunction in this group even when MRI abnormalities were
      present.

PMID- 9564130
TI  - The effect of Achievement orientation on response to success and failure in
      pediatric cancer patients.
AB  - OBJECTIVE: To assess the effects of different cognitive orientations focused on
      social comparison or self-comparison, followed by success or failure feedback, on
      mood, task persistence, and task difficulty choice in children with cancer.
      METHOD: Children with cancer (N = 79) and a group of age-matched controls (N = 72
      were randomly assigned in a 2 (Achievement Orientation) x 2 (Feedback) between
      subjects design. RESULTS: Between-group differences revealed that children with
      cancer chose more difficult tasks for the future than those in the comparison
      group, while the comparison subjects chose to persist longer with the problems
      than did children with cancer, with no significant differences on measures of
      mood. CONCLUSIONS: The beneficial effects of achievement orientation as a
      clinical manipulation may not be as robust as expected with a medically ill
      population, due to the apparent stability of achievement orientations.

PMID- 9564131
TI  - [Research progress on hereditary prostatic cancer. Families at risk should be
      surveyed and screening should be offered].

PMID- 9564132
TI  - [Etiology of the "sick building" syndrome is still not explained. But measures
      against mould, humidity and inadequate ventilation should be done].

PMID- 9564133
TI  - [Not only a hormonal relaxant. New discoveries show that progesterone can
      contribute to more efficient labor].

PMID- 9564134
TI  - [Keep the medical fees!].

PMID- 9564135
TI  - [Physicians' insurance company and ethics].

PMID- 9564137
TI  - [More responsible behavior should be expected from male physicians].

PMID- 9564136
TI  - [Unnecessarily complicated hygienic routines in diagnostic lumbar puncture].

PMID- 9564138
TI  - [Create a "feedback" forum for incompetent colleagues].

PMID- 9564139
TI  - [Gene for hereditary prostatic cancer has been located. New possibilities for
      early identification of men at risk].
AB  - Prostate cancer is currently the most common malignancy among men in Sweden, and
      an estimated 5-10 per cent of cases are hereditary. Several epidemiological
      studies have shown men whose close relatives are affected to be at 2-4-fold
      increased risk of developing prostate cancer. In a recent genetic linkage study
      of 91 Swedish and North American families with hereditary prostate cancer, the
      first susceptibility locus, HPC 1 (hereditary prostate cancer 1), was localised
      at positions 1q24-25 on the long arm of chromosome 1. In Sweden, we recommend men
      with a strong family history of prostate cancer to undergo annual prostate
      specific antigen testing and digital rectal examination from the age of 50.

PMID- 9564140
TI  - [Recurrent palsies--consider hereditary pressure neuropathy!].
AB  - Three cases of hereditary neuropathy with liability to pressure palsies (HNPP),
      characterised by the typical deletion in chromosome 17p11 2-12, are described in
      the article. The clinical manifestations were pain-free brachial plexus palsies
      in two patients (belonging to the same family), and multiple episodes of numbness
      and weakness in various nerves in the third patient. The clinical,
      electrophysiological, histological and genetic findings are reviewed.

PMID- 9564142
TI  - [Gold to eminent scientists].

PMID- 9564141
TI  - [Mental illness among immigrants and refugees. Are needs and available care
      adequate?].
AB  - A considerable proportion of the Swedish population are of immigrant or refugee
      origin. This puts new demands on psychiatric care. In Stockholm county,
      immigrants of non-Scandinavian origin are characterised by lower psychiatric care
      utilisation rates than are the remainder of the county population. Population
      studies of multi-ethnic suburban areas in west Stockholm have shown the non
      Scandinavian subgroup of the population to be characterised by somewhat lower
      utilisation of acute and short-term psychiatric care, as compared with native
      Swedes, but a clearly higher utilisation of primary psychiatric care facilities.
      Available evidence suggests the existence of several subgroups with high
      frequencies of mental ill-health in these areas. If sectorized psychiatry is to
      meet the demands of the population as a whole, economic prioritization is needed,
      as well as improved knowledge and methodology regarding cross-cultural
      psychiatry.

PMID- 9564143
TI  - ["Three kinds of charity" in psychiatry. All are needed when facing human
      psychiatric suffering].

PMID- 9564144
TI  - [Patient-physician communication. Physicians must be trained to tell bad news].

PMID- 9564145
TI  - [Talks can relieve damages caused by crisis and grief].

PMID- 9564146
TI  - [No one has been as meaningful as Jesus Christ].

PMID- 9564147
TI  - [The master Marx--a physician of social medicine].

PMID- 9564148
TI  - [Did glucan in indoor environment cause respiratory tract inflammation?].
AB  - Three children living in a house affected by mould manifested severe airways and
      general symptoms indicative of non-specific airways inflammation. Measurement of
      airborne (1-->3)-beta-D-glucan, a cell wall constituent in moulds, yielded values
      ranging from 22 to 115 ng/m3, as compared to normal values of some few ng/m3. On
      moving to relatives, all three children improved and could terminate medication
      after 2-3 weeks. The findings are consistent with previous reports of symptoms
      induced by exposure to mould, and suggest that quantification of viable organisms
      may not adequately reflect the exposure risk.

PMID- 9564149
TI  - [A SBU report on rheumatologic surgery. More should be referred for surgery.
      Centralization of difficult interventions].

PMID- 9564150
TI  - [Physicians' talks with patients have been analyzed. Three different types of
      images in physician-patient relations].

PMID- 9564151
TI  - [Epidemiology of osteoporosis].
AB  - Epidemiological studies have identified osteoporosis as a disease of significant
      public health impact and have delineated numerous potential risk factors.
      Nevertheless, it has proven difficult to establish preventive strategies for
      several reasons. First, there has been no final agreement on the definition of
      osteoporosis, which has hampered efforts to characterize the magnitude of the
      problem as a whole. Secondly, as osteoporosis is a multifactorial chronic
      disorder, effective programs for risk assessment and intervention depend on the
      development of complex disease models. In summarizing the contributions of
      epidemiological studies to the current understanding of osteoporosis this review
      intends to outline the scientific background for the European Vertebral
      Osteoporosis Study (EVOS) and its successors.

PMID- 9564152
TI  - [European Study of Vertebral Osteoporosis (EVOS): design and implementation in 8
      German study centers].
AB  - BACKGROUND: The European Vertebral Osteoporosis Study (EVOS), a multinational
      multicenter cross sectional study, was aimed to determine the prevalence of
      vertebral deformities, their risk factors and health impact. METHODS: Between
      1991 and 1993 4487 men and women aged 50 to 79 years were examined in 8 German
      study centres. Health impact, back pain and functional capacity were assessed in
      postal questionnaires. In medical interviews data was also collected on putative
      risk factors for osteoporosis including details on personal and medical history,
      drug use, diet, smoking, alcohol, exercise and gynaecological characteristics.
      Four thousand one hundred and twenty-two persons underwent a lateral X-ray
      examination of the thoracical and lumbar spine, representing a quarter of the
      16,000 European participants.

PMID- 9564153
TI  - [European Study of Vertebral Osteoporosis (EVOS): cooperation of participants and
      selection bias in Germany].
AB  - BACKGROUND: In population-based studies non-participation rates of about one
      third of the sample can be expected. The number of refusals may even be higher,
      if personal attendance of the subjects is requested. A different participation
      behaviour of the diseased and non-diseased may affect the prevalence estimation
      of a disease as well as the risk factor association. METHODS AND RESULTS: The
      European Vertebral Osteoporosis Study (EVOS) is an international, multicenter,
      cross-sectional survey in men and women aged 50 to 79 years. Within Europe 36
      centres recruited 17,342 participants. The 8 German centres contribute about one
      forth of the data. In Germany subjects were recruited in several steps: random
      sample drawing from population registries, initial postal questionnaire, medical
      interview, lateral X-rays of the thoracic and lumbar spine. Depending on the
      extent of participation a variable amount of sociodemographic data and
      information on subjective health is available from the non-reachable, non
      responders, and responders with incomplete and with complete examination. A
      comparison of the different participation groups showed, that especially old
      women were lost from the study. Compared to those, who only answered to an
      initial questionnaire, subjects, who were interviewed and X-rayed, more often
      suffered from back pain but reported a better functional capacity. This could be
      a hint on a selection of a population of the "worried well". CONCLUSION: On the
      whole the selection processes seem to have a minor influence on the outcome. The
      initial postal questionnaire turned out to be effective in collecting basic
      information from those who refused to attend a personal examination.

PMID- 9564154
TI  - [Morphometric analysis of roentgen images of the spine for diagnosis of
      osteoporosis-induced fracture].
AB  - The European Vertebral Osteoporosis Study (EVOS) is one of the largest studies to
      investigate the prevalence of osteoporosis related vertebral fractures in a
      population based cross-sectional study. One of the main tasks was to create
      standards and logistics to obtain uniform and comparable radiographs in all 36
      European centers. Furthermore the central reading of the X-rays and the
      morphometry of the vertebral bodies were 2 important challenges. This paper
      describes the standardized patient positioning and making of the radiographs as
      well as their morphometry, reading, and evaluation.

PMID- 9564155
TI  - [Prevalence of vertebral spinal deformities in women and men in Germany. EVOS
      group in Germany].
AB  - BACKGROUND: The prevalence of radiographically defined vertebral deformities, as
      a marker of vertebral osteoporosis, was calculated in a population based cross
      sectional survey in Germany. METHOD: Lateral spine X-rays were taken according to
      a standardized protocol and evaluated centrally. Three thousand nine hundred and
      eighty subjects (2064 male and 1916 female) aged 50 to 79 years, have been
      examined in 8 German centers. RESULTS: Based on McCloskey's method of deformity
      definition the age-standardized mean prevalence of vertebral deformities in
      Germany was 10.2% for males and 10.5% for females. Based on the definition by
      Melton/Eastell a significant higher prevalence was calculated (males 17.8%,
      females 18.7%). The prevalence increased with age in both sexes with a steeper
      increase in females. There was no difference in East and West German populations.
      There were substantial variations between the centers regarding the prevalence of
      deformities in females and males.

PMID- 9564156
TI  - [The reliability of radiologic findings for differential diagnosis of vertebral
      osteoporosis].
AB  - BACKGROUND: Radiologically identified vertebral deformities, e.g. wedge-, fish-,
      or crush-vertebrae are not always a consequence of local osteoporosis. Other
      frequent pathomechanisms include Morbus Scheuermann, degenerative changes, overt
      trauma, and congenital dysplasia. This requires differential diagnosis of
      vertebral deformities. Radiological classification criteria have to satisfy
      various methodological requirements to ensure reliability of the results.
      METHODS: Inter-rater reliability of more than 30 radiological findings was
      assessed in 4 German centres of the European Vertebral Osteoporosis Study (EVOS).
      One hundred randomly selected EVOS cases from the West-Berlin population, each
      contributing 2 lateral X-rays from the thoracic and lumbar spine respectively,
      were independently evaluated by 7 observers. All observers were medical doctors,
      4 of them heads or members of clinical radiological departments. Thus each
      observer read 200 radiographs. Radiological alterations in the form and structure
      of 13 vertebrale which were considered to be relevant for the differential
      diagnosis of osteoporosis were recorded in a standardized documentation form.
      Additionally global judgements (e. g. "osteoporotic spine" yes/no) were required.
      To quantify agreement Fleiss' kappa (kappa) for nominal data and multiple
      observers was used.

PMID- 9564157
TI  - [Burden of illness in vertebral deformities. EVOS group in Germany].
AB  - BACKGROUND: In the course of the European Vertebral Osteoporosis Study (EVOS)
      4060 men and women (target age 50 to 79 years; age and sex-stratified random
      samples from official population registers) were examined according to the
      standardized study protocol in 8 German study centres. METHODS: The study
      programme comprised an initial postal health questionnaire, a medical interview
      concerning risk factors and health impact and lateral X-rays of the thoracic and
      the lumbar spine. Vertebral deformities were defined morphometrically. The
      association between prevalent deformities and subjective health impairments was
      investigated using 2 different morphometric classifications. The following
      variables were included as indicators of reduced health: back pain ever/within
      the last 12 months/currently, back pain intensity, functional capacity (ADL
      list), graded back pain, subjective health, depression and grip strength.
      RESULTS: Bivariate analyses (chi(2) test, t-Test) as well as logistic regression
      analysis revealed significant associations between vertebral deformities and
      several negative health outcomes (odds ratios between 0.75 and 4.65, depending on
      definition of deformity). The associations were stronger in women.

PMID- 9564158
TI  - [Vertebral deformity as an index of osteoporosis-induced spinal fracture--an
      external validity construct based on bone density data].
AB  - BACKGROUND: In order to test the validity of vertebral morphometry for the
      assessment of prevalent vertebral osteoporotic fractures, we examined the
      association between vertebral deformities and bone mineral density (BMD). METHOD:
      The study population consisted of 595 postmenopausal women and 581 men aged 50 to
      82 years who participated in the baseline survey of the European Vertebral
      Osteoporosis Study (EVOS) in Germany and received BMD measurements by dual-X-ray
      absorptiometry (DXA) at the femur and the lumbar spine. RESULTS: In both sexes
      only vertebral deformities defined by more stringent morphometric criteria
      (McCloskey; Eastell 4 SD criterion) were significantly and inversely related to
      BMD (odds ratios 1.42 to 3.21 for a 1 SD [standard deviation] reduction in BMD; p
      < 0.05). The strength of the association depended on the stringency of the
      morphometric algorithm applied, and on the site of BMD measurement. The strongest
      associations were observed with femoral neck BMD in women and with BMD at the
      lumbar spine in men. In contingency analyses between vertebral deformities and
      osteoporosis (WHO criteria; European young female BMD reference values),
      vertebral deformities proved to be highly specific by all methods, even slightly
      more so in men (87.8 to 97.5%) than in women (86.3 to 96.7%). The predictive
      value of a positive test with respect to vertebral osteoporosis reached a maximum
      value of about 50% in both sexes. It further increased up to 72%, when the
      definition of osteoporosis was based on low BMD values at either the spine or the
      femoral neck, but only in women. CONCLUSIONS: In conclusion, for both men and
      women the likelihood of vertebral deformities to be related to osteoporosis
      increases with the stringency of the morphometric method, with a similar
      probability of major deformities to represent vertebral osteoporotic fractures in
      men as in women. Nevertheless, even the most stringent morphometric criteria are
      not sufficiently valid instruments for the assessment of the prevalence of
      vertebral osteoporotic fractures in epidemiological studies.

PMID- 9564159
TI  - [Bone density of spongiosa and cortical bone of the lumbar spine. Relations to
      sex, age and spinal deformities in a regional collective of the European Study of
      Vertebral Osteoporosis (EVOS)].
AB  - BACKGROUND AND METHOD: In an additional bone density measurement protocol to the
      European Vertebral Osteoporosis Study (EVOS) separate spongious and cortical
      density measurements (sQCT) were carried out at the first 3 lumbar vertebrae in
      293 volunteers (92 men and 201 women) in 3 Berlin regional centers. RESULTS: The
      spongious mineral density decreases from proximal to distal (L1 to L3), the
      cortical density increases from proximal to distal, mainly in men. Men showed no
      significant decrease of cortical density and a lower decrease of spongious
      density with age compared to women. A comparison of bone mineral density with
      vertebral height indices of McCloskey/Kanis, Eastell/Melton and Felsenberg showed
      significant differences of spongious density between a group with normal
      vertebral height and a group with at least one pathologically degraded vertebra.
      Individuals with osteoporosis according to the WHO-definition showed a higher
      prevalence of vertebral deformities. No significant loss of cortical density was
      observed in these people.

PMID- 9564160
TI  - [Osteosonography of the phalanges of men].
AB  - BACKGROUND: The distal metaphysis of the first phalanx of the fingers II to V is,
      like the vertebral body, a useful site for the measurement of mineralisation and
      structure of the bone, because of the simultaneous presence of compact and
      trabecular bone. METHOD: With an osteosonographic device (DBM sonic 1200, IGEA,
      Italy) we measured in 38 young and healthy men, 14 elderly and healthy men, 18
      men with osteopenia, 8 men with osteoporosis and vertebral fractures and 10 men
      with long-standing cortisone medication, the adSOS (amplitude-dependent speed of
      sound) and the UBPS (ultrasound bone profile score) at the phalanges, as well as
      bone mineral density (BMD) at lumbar spine using dual-X-ray absorptiometry (DXA).
      RESULTS: There was no correlation between adSOS or UBPS and lumbar BMD (DXA).
      There was a significant positive correlation between adSOS and UBPS, r = 0.826 (p
      < 0.00001). AdSOS declined with age (r = 0.694, p = 0.021); the UBPS was not age
      dependent (r = -0.15, p = n.s.), as expected. AdSOS and UBPS could discriminate
      significantly between the young and healthy controls and the men with
      osteopenia/vertebral fractures or oral steroids (p < 0.00001). The DXA could be
      significantly discriminate all healthy controls from the patients with osteopenia
      or vertebral fractures. It could not significantly discriminate the healthy
      controls from the patients taking oral glucoconticoids. Only the UBPS could
      significantly discriminate this group from the healthy controls. CONCLUSION:
      These results show, that adSOS and UBPS are precise parameters to be measured at
      the phalanges. The detection level of pathological changes in osteoporosis are
      similar between adSOS and lumbar BMD (DXA) and improved by using UBPS. This might
      be explained by the influence of structural changes in bone on UBPS, rather than
      changes in bone mineral alone. Prospective studies have to clarify the role of
      adSOS and UBPS in fracture prediction.

PMID- 9564161
TI  - [Age related decrease of high density lipoproteins (HDL) in women after
      menopause. Quantification of HDL with genetically determined HDL arylesterase in
      women with healthy coronary vessels and in women with angiographically verified
      coronary heart disease].
AB  - BACKGROUND: The decline in the concentration of high density lipoproteins (HDL)
      observed in postmenopausal women is thought to contribute to the increasing
      incidence of coronary artery disease (CAD) after menopause. Human serum
      arylesterase (EC 3.1.1.2) is exclusively associated with HDL. We therefore
      investigated possible differences in the decline of HDL-levels and of HDL
      subfractions HDL2 and HDL3 between postmenopausal women without and with
      angiographically documented CAD. PATIENTS AND METHODS: HDL-, HDL2-and-HDL3-
      concentrations were studied in postmenopausal women with angiographically
      documented CAD (n = 24; 51 to 72 years mean: 62 years) and compared to HDL
      parameters of women without CAD (n = 22; 51 to 81 years, mean: 58 years).
      Arylesterase activities of HDL2-and HDL3-subfractions and HDL2-cholesterol
      concentrations were determined after differential precipitation with polyethylene
      glycol (4.7 mM PEG). Phenotyping of HDL-arylesterase was achieved in CAD patients
      and in women without CAD after determining hydrolysis of arylesterase substrates
      paraoxon (PO) and phenylacetate (PA) by calculating paraoxonase/arylesterase
      activity ratios R (R = [PO]/[PA] x 1000): phenotype A (n = 26) with R < 2.5,
      phenotype AB (n = 16) with 5.0 < R < 10.7, and phenotype B (n = 4) with R > 13.5.
      RESULTS: In postmenopausal women with documented CAD, as compared to women
      without CAD, HDL-cholesterol (55 +/- 3 mg/dl vs. 69 +/- 3 mg/dl HDL2-arylesterase
      (25 +/- 1 kU/l vs. 33 +/- 2 kU/l), and HDL3-arylesterase (89 +/- 4 kU/l vs. 106
      +/- 5 kU/I) were found to be significantly reduced. Analysis of the correlation
      of lipid parameters and age revealed in CAD patients, but not in postmenopausal
      women without CAD, a significant increase of total cholesterol (r = 0.42), and
      significant reductions of both HDL2-arylesterase (r = -0.47) and HDL3
      arylesterase (r = 0.74) with increasing age. In contrast, HDL-cholesterol (r = 
      0.14) and HDL2-cholesterol (r = -0.06) of CAD patients showed only slight and non
      significant reductions with age. Since HDL3-arylesterase was found to be age
      dependently reduced in women without CAD (r = 0.17), HDL2-arylesterase of
      postmenopausal women, among all lipid parameters showed the most pronounced
      differences between women without CAD and CAD patients. The age-dependent
      decrease of HDL2-arylesterase in postmenopausal women with CAD does not result
      from an increased frequency of B-allele carriers in the subgroup of CAD patients
      with an age above the median (64 years). CONCLUSION: Genetically determined serum
      HDL-arylesterase is well suited to quantify HDL in postmenopausal women without
      and with CAD. HDL2-arylesterase of postmenopausal women should be evaluated as a
      screening parameter for both primary and secondary CAD prevention.

PMID- 9564162
TI  - [1997 gastroenterology update--II].

PMID- 9564163
TI  - [Quantitative cultures in diagnosis of pneumonia--a method for routine
      practice?].
AB  - Quantitative cultures of respiratory secretions represent a valid technique for
      the diagnosis of ventilator-associated pneumonia. Contamination, colonization and
      true infection can be differentiated with a reasonable specificity using
      established cut-offs of bacterial colony counts. Quantitative investigations
      provide local epidemiological databases as a framework for empirical
      antimicrobial policies and may also prove helpful in the guidance of individual
      antimicrobial therapy. Another reasonable indication is HIV-associated pneumonia.
      However, the use of this technique in routine practice is hampered by the high
      expertise and experience that will be necessary to be successfully used.
      Nevertheless, in view of the need to identify bacterial susceptibility patterns,
      at least large treatment centers should routinely use this most powerful
      diagnostic technique.

PMID- 9564164
TI  - [Coccidioidomycosis as the cause of granulomatous hepatitis].
AB  - The case of 36-year-old man is reported who fell ill with a febrile infection,
      shortly after returning from several weeks to Mexico. EXAMINATION: Chest X-ray
      revealed a pulmonary infiltration. Also, the levels of liver function tests
      (gamma-GT, alkaline phosphatase, SGOT, SGPT) were clearly increased. As there
      were no signs of extended bile ducts in ultrasonics, a liver biopsy was
      indicated. The histology showed a granulomatous hepatitis. DIAGNOSIS: The
      exposure during the Mexico-trip, the pulmonary infiltration, the histology and
      the significant raised titers in specific serological tests led to the diagnosis
      of a general infection by the fungus coccidioides immitis. In addition to
      pathogenetic aspects of coccidioidomycosis the diagnostic approaches and relevant
      therapeutic strategies are discussed.

PMID- 9564165
TI  - [Successful therapy of phenprocoumon poisoning with plasmapheresis].
AB  - A case report demonstrates a possibility of successful treatment in a patient
      with high-dosage phenprocoumon intoxication. CONCLUSION: The use of
      plasmapheresis is an appropriate method to treat phenprocoumon-intoxicated
      patients by exchange of endogenous with supplied fresh frozen plasma.

PMID- 9564166
TI  - [Supraventricular tachycardia, III. Pre-excitation syndrome--diagnosis and
      therapy].

PMID- 9564167
TI  - [Clinical studies in oncology. Relevance, design, ethical considerations].
AB  - BACKGROUND: Clinical research in oncology includes the evaluation of diagnostic,
      prognostic and therapeutic parameters in order to establish standards for the
      different tumor entities. Prerequisite is the retrospective and prospective
      analysis of large patient groups with established statistical methods. New
      potentially better strategies have to be compared in randomised studies with the
      respective "gold standard". The central role of clinical studies for evaluation
      and optimisation of therapy can be considered as moral obligation to included the
      maximal possible number of patients in clinical studies. However, only a small
      number of tumor patients in Germany is treated in controlled clinical studies.
      Reasons are lack of organisational structures, but also ethical considerations.
      STUDY DESIGNS: In this article several models for clinical studies are discussed
      with respect to their statistical significance, indication, and potential ethical
      objections. CONCLUSION: Aim of the discussion is to increase the acceptance of
      the necessity of clinical studies for evaluation and optimisation of therapeutic
      options in oncology.

PMID- 9564168
TI  - [Gastritis and thoracic pain. Churg-Strauss vasculitis].

PMID- 9564169
TI  - [Evolutionary quality assurance. A new concept for improving process and outcome
      quality].
AB  - BACKGROUND: The concept evolutionary quality assurance is a new, non-mandatory,
      open peer review process for in-patients settings. METHOD: Ten medical charts
      (with radiographs) from participating hospitals were randomly chosen and assessed
      using a prespecified questionnaire (total 134). Individual inadequacies had to be
      justified on a case by case level. Reviewer and reviewee are known by names,
      allowing subsequent discussions on content between reviewer and reviewee prior to
      a final judgement. The final analysis was performed anonymously and communicated
      to the participants after completion of the process. Patients had to give their
      consent to the review process. The report, however, is not part of the medical
      patient file, so that access is not warranted. For the first cycle, all lung
      clinics and departments throughout Germany were asked to participate. 35 chest
      hospital (approximately 50%) agreed to participate. RESULTS: Data analysis
      revealed that almost all detected inadequacies were apparent, i.e. discussions on
      the discordant interpretation of diagnostic and therapeutic strategies rarely
      occurred (0.25%). Final analysis of the evaluation performance of reviewers
      judged less than 5% and 14% judged more than 30% of all quality inadequacies.
      CONCLUSIONS: The quality assurance process is comparably cheap and can be
      implemented without delay, because standards for reference values are not
      required. The structure allows adaptation in all areas of clinical medicine.

PMID- 9564170
TI  - Sterol regulatory element binding proteins (SREBPs): controllers of lipid
      synthesis and cellular uptake.
AB  - Mammalian cells use an exquisitely sensitive mechanism to control the amount of
      cholesterol and fatty acids in their membranes. This process relies on a feedback
      system that adjusts the rates of transcription of genes encoding the low density
      lipoprotein receptor and multiple enzymes in the cholesterol and fatty acid
      biosynthetic pathways. When cellular cholesterol levels are depleted, these genes
      are all transcribed in abundant amounts, and their transcription is repressed
      when sterols build up within the cell. Until recently, the mechanism of this
      regulation was elusive. How do cells sense the level of a membrane-embedded lipid
      such as cholesterol and how is this information transmitted to the nucleus where
      gene transcription is regulated? Answers are now beginning to emerge from the
      study of a newly discovered family of transcription-regulating proteins called
      sterol regulatory element binding proteins.

PMID- 9564171
TI  - Mechanisms and functions of vitamin D.
AB  - The vitamin D hormone, 1,25-dihydroxyvitamin D3, functions by way of a nuclear
      receptor (vitamin D receptor [VDR]) in a manner analogous to the other members of
      the steroid-thyroid hormone superfamily. Although the vitamin D receptor has been
      cloned, its three-dimensional structure remains unknown. The VDR binds to the
      direct repeat response elements called DR-3 in the promoter region of target
      genes to stimulate or suppress transcription of those genes encoding for proteins
      that carry out a wide variety of functions. The binding of the VDR to a DR-3
      requires the presence of its ligand and a companion protein, namely the RXR group
      of retinoid receptors. The RXR binds to the 5' arm of the response element while
      the VDR binds to the 3' arm. In addition, the transcription factor TFIIB has been
      shown to bind VDR but there is currently no evidence that a co-repressor or co
      activator of VDR is also involved. Phosphorylation of VDR in the transcription
      complex occurs as does bending of the DNA prior to the initiation or suppression
      of transcription. As VDR has been detected in cells not previously thought to be
      target organs, scientists continue to discover new functions of vitamin D. Among
      these new functions are those noted in the immune system. Experiments in mice
      have illustrated that the autoimmune diseases of multiple sclerosis and
      rheumatoid arthritis can be successfully treated with the vitamin D hormone and
      its analogs. New experiments illustrating the use of the vitamin D hormone and
      its analogs in suppressing transplant rejection indicate that these compounds may
      be superior to cyclosporin and may not have the side effects attributed to the
      cyclosporin immunosuppression therapies.

PMID- 9564172
TI  - Iron and gene expression: molecular mechanisms regulating cellular iron
      homeostasis.
AB  - In recent years, specific post-transcriptional mechanisms in the cytoplasm of
      vertebrate cells have been elucidated that directly affect the stability and
      translation of mRNAs coding for central proteins in iron metabolism. This review
      shall focus primarily on these mechanisms. Other levels of control, either
      affecting gene transcription and/ or related to the function of iron-capturing
      substances and transmembrane transport, are also likely to exist and to influence
      the iron balance and utilization. They are, however, much less clear.

PMID- 9564173
TI  - Fatty acids in control of gene expression.
AB  - During the recent decade or so, there has been tremendous development in our
      understanding of the mechanism of action of certain nutrients. This process has
      been fostered primarily by the application of modern molecular and cellular
      biological techniques within the discipline of nutrition. This novel approach,
      which is now known as molecular nutrition, has revealed that many nutrients and
      vitamins seem to act essentially in the same way as steroidal hormones, i.e., by
      binding to soluble intranuclear receptors. The ligand-receptor complexes then
      bind to promoters of regulated genes, thereby affecting their rate of
      transcription.

PMID- 9564174
TI  - Vitamin D polymorphisms and calcium homeostasis: a new concept of normal gene
      variants and physiologic variation.
AB  - The initial findings on the vitamin D receptor have opened the field of the
      genetics of osteoporosis to targeted genetic studies and may open the way to
      genome scan approaches. Interaction between genetics, the environment, and
      lifestyle factors will also be an important target for future research.
      Understanding the physiology of such gene effects will likely open the way to
      more specific treatments and the selection of more appropriate and effective
      treatment options.

PMID- 9564175
TI  - Hemochromatosis and iron needs.
AB  - Although iron is an essential dietary requirement, the amount absorbed by the
      body is well regulated and depends on body iron stores and on dietary iron
      availability. There is very little iron excreted under normal conditions. Iron
      deficiency is a worldwide problem but iron overload, as seen in the inherited
      disease, hemochromatosis, is a major cause of morbidity in some Caucasian
      populations. This is a problem particularly where there is an adequate dietary
      iron intake and especially in males. A mutation has recently been described in an
      MHC Class l-like gene (HFE) that encodes for a protein (HFE) of 343 amino acids.
      The molecule contains a signal sequence peptide-binding region, alpha, and
      alpha(2) domains, and an immunoglobulinlike alpha(3) domain, in addition to a
      transmembrane region and a small cytoplasmic tail. It is a candidate gene for
      hemochromatosis. Several possibilities as to the function of this gene and the
      corresponding protein have been suggested but none has yet been confirmed. The
      mutation has been detected by several different groups in 80%-100% of subjects
      with the disease. However, in one study, 18%-20% of patients with the mutation
      did not exhibit significant iron overload. The discovery of this gene has
      important implications for both clinical studies and the elucidation of the
      pathways of iron metabolism.

PMID- 9564176
TI  - Leptin, leptin receptors, and the control of body weight.
AB  - The assimilation, storage, and disposition of nutrient energy constitute a
      complex homeostatic system central to the survival of both prokaryotic and
      eukaryotic organisms. In vertebrates, and especially among land dwelling
      mammalian species, the ability to store large quantities of energy-dense fuel in
      the form of adipose tissue triglyceride permits survival during prolonged periods
      of food deprivation. In order to maintain such fuel stores during times of
      dietary scarcity or surfeit, some balance between energy intake and expenditure
      must be achieved. Lesions of the hypothalamus alter body weight suggesting that
      this brain region regulates nutritional state. These and other studies led to the
      hypothesis that body weight was regulated by a feedback loop in which peripheral
      signals reported nutritional information to an integratory center in the brain.
      However, the identity of these nutrition signals proved elusive.

PMID- 9564177
TI  - The implications of genetic diversity for nutrient requirements: the case of
      folate.
AB  - "The existence of chemical individuality follows of necessity from that of
      chemical specificity, but we should expect the differences between individuals to
      be still more subtle and difficult of detection. Indications of their existence
      are seen, even in man,... in the quantitative differences in those portions of
      the end products of metabolism which are endogenous and are not affected by
      diet.... Even those idiosyncracies with regard to... articles of food which are
      summed up in the proverbial saying that what is one's man meat is another man's
      poison, presumably have a chemical basis."

PMID- 9564178
TI  - Diet, activity, and other health-related behaviors in college-age women.
AB  - Morbidity and mortality data for young women in the United States reflect several
      health risk behaviors for both acute and chronic disease development. Available
      data suggest that young women's diets are high in total and saturated fat and low
      in fiber, fruits, vegetables, and dairy products. As a result, diets of young
      women are frequently low in iron, folate, and calcium. Prevalence of overweight
      continues to increase significantly in this population, but inappropriate body
      image concerns and disordered eating patterns are also common. Inactivity,
      smoking, and weight cycling are patterns that appear to begin early in women's
      lives. Some data suggest that young women value nutrition quality and are more
      likely to attempt positive changes than are young men.

PMID- 9564179
TI  - On the methods for studying the mechanisms and bioavailability of iron.
AB  - Studies of the molecular mechanisms involved in the absorption and
      bioavailability of iron are important to attempts made worldwide to control the
      high incidence of iron-associated disorders. The ultimate objective of these
      studies is to develop methods that are relevant to iron bioavailability and
      interactions in humans. However, a comprehensive understanding of the chemical
      and physiologic mechanisms that influence iron bioavailability is necessary to
      achieve this goal. Initial studies using in vitro and animal models offer the
      potential for flexibility and manipulation of experimental variables that could
      provide valuable information toward the understanding and improvement of food
      iron bioavailability.

PMID- 9564180
TI  - Amyotrophic lateral sclerosis: a lesson in deficiency diseases.
AB  - Amyotrophic lateral sclerosis (ALS) is an age-dependent degeneration of motor
      neurons in the central nervous system. ALS is not caused by faulty nutrition.
      Recent data suggest that ALS could be an oxidative neurotoxicity induced by a
      mutation in the SOD1 protein. This finding extends beyond the simple loss of an
      antioxidant enzyme.

PMID- 9564181
TI  - The cloning and characterization of a novel cytochrome P450 family, CYP26, with
      specificity toward retinoic acid.
AB  - A new family of cytochrome P450 enzymes, CYP26, has been cloned and characterized
      in zebra fish, human, and mouse tissues. CYP26 displays specificity toward
      retinoic acid and it may function as an important regulator or differentiation
      and a possible modulator of disease states by controlling retinoid concentration
      and homeostasis.

PMID- 9564182
TI  - Inhibition of cellular uptake of folate by blocking synthesis of the membrane
      folate receptor.
AB  - The folate receptor, bound to the plasma membrane through a
      glycosylphosphatidylinositol anchor, requires both sphingolipids and cholesterol
      in the membrane for full activity. In recent studies, treatment of cells in
      culture with the mycotoxin fumonisin B1, which inhibits sphingolipid synthesis,
      virtually abolished uptake of 5-methyltetrahydrofolate.

PMID- 9564183
TI  - Identification of Nramp2 as an iron transport protein: another piece of the
      intestinal iron absorption puzzle.
AB  - Although a number of iron-binding proteins have been identified, the roles for
      specific proteins in mediating iron absorption have not been definitively
      assigned. Two recent papers report the identification of an iron transport
      protein that may be responsible for movement of iron from the intestinal lumen
      into the enterocyte. Coupled with the recent identification of the protein
      mutated in hemochromatosis, researchers are now establishing a clearer picture of
      the mechanism of intestinal iron absorption.

PMID- 9564184
TI  - [Almitrine in therapy of chronic obstructive respiratory tract diseases with
      hypoxemia--a clinical multicenter study comparing 2 dosages].
AB  - In an 8-month prospective, placebo-controlled multi-centre trial involving 64
      hypoxaemic COPD patients (mean +/- SD age, 64 +/- 8 years, paO2, 57 +/- 7 mmHg,
      paCO2, 41 +/- 6 mmHg), we compared the efficacy and acceptability of two
      different dosages of almitrine, 75 and 100 mg. 21 patients received continuous
      treatment with almitrine (75 mg), 23 sequential treatment (100 mg, one month of
      placebo after three months treatment), and 20 were in the placebo group. As
      defined by the inclusion criteria, none of the patients had clinical or
      subclinical signs of peripheral neuropathy. Clinical examinations, blood gas
      analyses and determinations of plasma almitrine levels were performed monthly.
      Patients underwent spirometry and detailed neurological examination upon entry
      and at the end of the trial. The percentage of drop-outs was considerably higher
      among patients under medication (59%) as compared to placebo (10%, p < 0.001)
      which was particularly due to impaired compliance in the almitrine groups.
      Comparing arterial paO2 or paCO2 over time by analysis of variance, there was no
      significant effect of medication on blood gases. However, in patients receiving
      100 mg almitrine daily, paO2 was significantly increased vs. placebo after four
      and six months of treatment, and in patients receiving 75 mg almitrine, mean
      paCO2 was significantly lowered vs. placebo after four months of medication (t
      test, p < 0.05). Neurological findings did not differ between treatments and over
      time. In conclusion, only certain individual patients may benefit from a
      treatment with 100 mg almitrine whereas the effect of the 75 mg dosage on paO2
      did not differ from placebo.

PMID- 9564185
TI  - [Lymphocytes in bronchoalveolar lavage (BAL). Why are kinetic parameters for
      interpretation of BAL findings important for the patient?].

PMID- 9564186
TI  - [Boerhaave syndrome: a rare cause of acute thoracic pain].
AB  - In a 74-year old female patient suffering from acute thoracic pain, vomiting, and
      dyspnoea, the diagnosis of Boerhaave's syndrome was made. After medical treatment
      the patient was dismissed in a sufficiently satisfactory condition. If symptoms
      like vomiting, severe thoracic pain, pneumomediastinum, pneumothorax or
      hydropneumothorax on the left side occur, a rupture of the oesophagus should be
      taken into account especially in case of abuse of alcohol. The early diagnosis is
      decisive for the course of the disease and a lethality reduction.

PMID- 9564187
TI  - [Unilateral pulmonary vein atresia in early adulthood].
AB  - Unilateral pulmonary vein atresia is a rare condition in adults that may cause
      serious diagnostic problems because of unspecific clinical findings. A 28-year
      old female patient is described who presented with signs of recurrent pulmonary
      embolism with shortness of breathing, unilateral thoracic pain and several
      episodes of haemoptysis. Ventilation and perfusion scans showed a total lack of
      perfusion in the right lung with only slight disturbance of ventilation. However,
      no marked increase of pulmonary artery pressure and no signs of a recent
      thrombosis of peripheral veins were found. Transoesophageal echocardiography and
      pulmonary angiography in combination with aortography revealed the diagnosis of
      unilateral pulmonary vein atresia with abnormal branches of bronchial arteries.
      There is a considerably left-to-right shunt with return of flow from the
      bronchial arteries to the right and afterwards to the left pulmonary artery.
      Clinical, radiological and nuclear medical findings as well as therapeutical
      options are described.

PMID- 9564188
TI  - [Obstructive sleep apnea in the child: an interdisciplinary treatment concept
      with special reference to craniofacial changes].
AB  - Diagnosis and therapy of obstructive sleep-related breathing disturbances SRBD in
      adults may not be applied without hesitation to children. SRBD in newborn and
      infants are often due to craniofacial disturbances (Pierre Robin syndrome,
      Goldenhars syndrome etc.), obesity is of minor importance. More than 30 infants
      with SRBD and craniofacial changes have been diagnosed and successfully treated
      over a 2-year period. Conservative therapy starts immediately after birth. The
      first step in newborn with Pierre Robin syndrome, for instance, is prone position
      for protrusion of tongue and mandible and mandibular growth stimulation.
      Intermediate nightly nasopharyngeal tubes are an alternative to nCPAP-/BiPAP
      treatment. Conventional orthopaedic/orthodontic treatment should not be
      neglected, even if it takes years to become effective. Surgical therapies are
      able to support, sometimes to replace or at least to shorten conservative
      methods. In rare cases when prone position in combination with palatal plates in
      cases of Robin syndrome, for instance, are not fully effective, mandibular
      extension is indicated. Aplasia or defects demand adequate surgical
      reconstruction, even if this does not necessarily mean abolishment of SRBD. In
      contrast to adults adenotonsillectomy is highly effective in infants and does not
      only reduce SRBD, but also improves nasal breathing and thus positively
      influences facial growth. A relatively new method is gradual mandibular
      distraction osteogenesis according to Ilizarov, which also enhances soft tissue
      growth. Maxillary and mandibular advancement osteotomies should not be considered
      before the termination of facial growth. Thanks to this refined treatment concept
      we were able to avoid tracheotomies in children during the past few years.

PMID- 9564189
TI  - [Safety aspects of bronchoalveolar lavage in risk patients in childhood-
      continuous end-expiratory pCO2 monitoring].
AB  - Although bronchoalveolar lavage (BAL) is a useful tool even in childhood
      pulmonary diseases, only little is known about the problems attendant to its use.
      Hence, we investigated from a total of 212 rigid bronchoscopy procedures 22
      patients of 1-10 years of age. General inhalation anaesthesia was performed and
      BAL was carried out using a paediatric standardised protocol. BAL volume was
      adjusted to body weight. Before BAL and 2, 7 and 20 minutes after BAL capillary
      blood gas, blood pressure, heart rate and SaO2 were measured. Continuously end
      tidal PCO2 (ET (PCO2) measurement was done by using a catheter placed in the main
      stream bronchus. Mean ET PCO2 increased from 39.6 +/- 9.5 mmHg to 45.7 +/- 6.87
      mmHg. Concomitantly mean capillary PCO2 increased from 46.68 +/- 10.7 mmHg to
      50.1 +/- 10.47 mmHg. Correlation of ET PCO2 compared to cap PCO2 was good (r =
      0.89). One patient showed desaturation up to 72% another patient hypercapnia up
      to 77 mmHg. We conclude that generally speaking BAL is a safe procedure, even in
      high-risk patients. Complications are minor and of little consequence to the
      patient. However, severe unforeseen events may occur. Therefore, bronchoscopy and
      bronchoalveolar lavage should not be performed without availability of an
      intensive-care unit.

PMID- 9564190
TI  - [Submaximal spiroergometric stress study in patients with mixed dust
      pneumoconiosis].
AB  - Disabilities of patients with coal-workers' pneumoconiosis (CWP) are currently
      estimated by changes in lung function at rest and the degree of dust equivalents
      in chest x-ray (ILO-classification 1980). Functional disturbances during exercise
      are not taken into consideration on a regular basis. We assumed that standardised
      sub-maximal exercise tests might be useful even in disabled patients to give
      additional information on functional disabilities of patients with CWP. The
      impact of low-grade anthracosilicosis on ventilation and gas exchange during
      exercise was assessed in 20 patients (all male, age 64.55 +/- 3.78 years) and 24
      healthy volunteers (all male, age 58.13 +/- 4.68 years, never dust exposed). Data
      were also analysed according to ILO classification subgroups (group 1: ILO
      classification 1/0 to 1/2, n = 11; group 2: ILO-classification 2/1 to 2/2, n =
      9). Heart rate (HR), minute ventilation (VE), ventilatory equivalent for O2
      (VE/VO2), ventilatory equivalent for CO2 (VE/VCO2), O2 uptake (VO2)CO2 output
      (VCO2), end-tidal oxygen partial pressure (PetO2), end-tidal carbon dioxide
      partial pressure (petCO2) and estimated dead space to tidal volume ratio (VD/VT)
      were determined breath-by-breath during a 50 watts constant work load protocol on
      an exercise bicycle. The VE/VO2 (patients: 32.9 +/- 4.2; controls: 25.7 +/- 2.9;
      p < 0.001), the VE/CO2 (patients: 39.4 +/- 4.6; controls; 31.0 +/- 3.9), the VE
      (patients: 30.1 +/- 5.6, controls: 23.5 +/- 3.0; p < 0.001) and the PetO2
      (patients 115.6 +/- 4.8; controls: 99.1 +/- 27.4; p < 0.05) at an exercise of 50
      watts were significantly higher in the patients' group, the PetCO2 (patients:
      38.4 +/- 4.5; controls: 44.0 +/- 4.1) were significantly lower in the patients'
      group. The comparison of patients subgroups did not reveal any significant
      differences between group 1 and group 2. A higher VE/VO2 during 50 watts of
      exercise is attributable to an increased ventilation/perfusion mismatch. There
      was no correlation between the radiological grade of the CWP (ILO classification)
      and the ventilation and gas exchange during exercise. We conclude that a sub
      maximal spiroergometry with a 50 watts constant work load might serve as a
      sensitive and easy to apply procedure add information about the functional
      impairment in CWP. The exercise test should be included in the evaluation for
      disability benefits.

PMID- 9564191
TI  - Psychiatric research interview for substance and mental disorders:
      phenomenologically based diagnosis in patients who abuse alcohol or drugs.
AB  - The Psychiatric Research Interview for Substance and Mental Disorders (PRISM) is
      a psychiatric diagnostic interview designed to diagnose DSM-IV substance and
      mental disorders in patients who abuse alcohol or drugs. Primary disorders tested
      in the DSM-III-R version of the interview showed improved reliability over
      existing instruments, and substantially improved reliability for major depressive
      disorder (MDD). Developments for DSM-IV include a systematic set of procedures
      for differentiating primary disorders, substance-induced disorders, and the
      expected effects of intoxication and withdrawal based on the phenomenology of
      symptoms in conjunction with alcohol and drug use. A longitudinal version of the
      PRISM provides data on remission and relapse that can be analyzed with survival
      methods. Pilot and preliminary testing of the DSM-IV and longitudinal versions of
      the instruments is presented. By making use of psychometric principles,
      particularly the need to reduce criterion variance, these instruments can clarify
      some of the longstanding issues in the diagnosis of patients who abuse alcohol
      and drugs.

PMID- 9564192
TI  - Computerized self-assessment of psychosis severity questionnaire [COSAPSQ] in
      schizophrenia: preliminary results.
AB  - We attempted to develop and validate a computer-driven patient self-rated
      questionnaire [COSAPSQ] which should provide a reliable, rapid, and inexpensive
      method to assess symptom severity in patients with psychosis in general and with
      schizophrenia in particular. After giving informed consent patients with DSM-IV
      schizophrenia or schizoaffective disorder were interviewed and rated on PANSS and
      CGI. Subsequently patients completed the COSAPSQ questionnaire (61 multiple
      choice questions) in the presence of an observer. The analysis of the first 29
      rating sets showed that patients with CGI scores of 3-6 completed the
      questionnaire in a mean time of 21.6 minutes. One-way analysis of variance of
      COSAPSQ total scores by CGI ratings was highly significant (p < .001). COSAPSQ
      total scores correlated well with PANSS total, general and positive scores and
      with CGI (all r = 6-.7; p < .005). The next versions of the questionnaire will
      require some adjustments: overall fewer questions, improved assessment of
      negative symptoms, and improved graphic presentation.

PMID- 9564193
TI  - Developing and comparing treatment strategies: an annotated portfolio of designs.
AB  - Useful clinical strategies are adaptive, specifying the sequence of treatments
      that are alternatives, what it means for the treatment to "work," the rules for
      abandoning a treatment, and the subsequent treatments. Because combinatorial
      complexity precludes comparison of every possible whole strategy, current
      experiment-based methods rely on comparisons among a few options at particularly
      crucial decision points, and strategies are pieced together from scraps of
      information. Nonexperimental methods for strategy development offer a seductive
      alternative, but their advantages may be illusory. Clinical investigators deploy
      a wide range of study designs to compare treatment strategies in mental health.
      This article organizes the types of designs by their purpose and annotates this
      list with comments on the strengths and weaknesses of each type. We conclude with
      some general comments on the overall process of development of treatment
      strategies.

PMID- 9564194
TI  - The problem of measurement error in multisite clinical trials.
AB  - The implementation of a multisite, randomized, clinical psychopharmacologic trial
      involves a substantial investment of time and effort on the part of all
      participants. Because of their complexity, such clinical trials present unique
      methodological and design challenges. Indeed, it is not uncommon for such studies
      to conclude with uninterpretable results, due in part to such methodological
      pitfalls. It has been suggested that clarification of such methodologic dilemmas
      is one of the most important challenges facing the future of industry-sponsored
      psychopharmacologic drug development. Among the many factors that may contribute
      to problematic clinical trial results, error in measuring the phenomena being
      studied is of particular concern. In this article, we describe the outcome of an
      intensive series of interrater reliability training sessions for the 17-item
      Hamilton Depression Rating Scale conducted at the start of a Phase II multisite
      clinical drug trial. The data underscore the magnitude of error present in such a
      test setting and provide preliminary evidence for the potential effect of this
      problem on the detection of clinical change.

PMID- 9564195
TI  - Adjusting sample size for anticipated dropouts in clinical trials.
AB  - Statistical models for calculating sample sizes for controlled clinical trials
      often fail to take into account the negative impact that dropouts have on the
      power of intent-to-treat analyses. Empirically defined dropout correction
      coefficients are proposed to adjust sample sizes for endpoint analysis of
      variance (ANOVA) and analysis of covariance (ANCOVA) that have been initially
      calculated assuming complete data. The implications of type of analysis (change
      score ANOVA or ANCOVA), correlational structure of the repeated measurements
      (compound symmetry or autoregressive), and percentage of dropouts (20% or 30%)
      are considered, together with other less influential design and data parameters.
      We recommend the use of ANCOVA to correct for baseline differences and for time
      in-study if there is a nonspecific change across time. Given a realistic
      autoregressive (order 1) correlational structure for the repeated measurements
      and a proposed endpoint ANCOVA, the empirical results support the common practice
      of increasing calculated sample size by the anticipated number of dropouts. The
      previous rationale has been to retain a requisite number of "completers" on which
      to base statistical inferences. We believe the present results provide the first
      documentation of the relevance of that strategy for intent-to-treat analyses in
      which the incomplete data for dropouts must be included. Based on comparative
      power analyses, the strategy also seems appropriate for maintaining the power of
      mixed-model regression analyses, simple regression on a normalized time scale,
      and analyses of trends fitted to imputed scores for dropouts.

PMID- 9564196
TI  - Should we use antidepressant medications for children and adolescents with
      depressive disorders?
AB  - Most of the randomized controlled trials (RCTs) on the acute treatment of
      children and adolescents with major depressive disorder (MDD) have shown about 50
      percent response to both tricyclic antidepressants (TCAs) and placebo. In
      contrast, a recent RCT found fluoxetine superior to placebo for the treatment of
      depressed youth. Cognitive-behavioral psychotherapy has also been found
      efficacious for the treatment of youth with depression. Therefore, the use of
      medications in particular TCAs, as the first line of treatment for youth with
      mild to moderate MDD has been questioned. However, some subgroups of patients,
      especially those who are unable or unwilling to undergo psychotherapy and those
      with psychosis, bipolar depression, severe depressions, or recurrent episodes,
      may benefit from initial treatment with antidepressants. Further research on the
      continuation and maintenance treatment phases of depression as well as treatment
      for dysthymia, treatment-resistant depression, and other subtypes of depressions
      is warranted.

PMID- 9564197
TI  - Aggression classification and treatment response.
AB  - This preliminary study investigated whether the aggression subtypes derived from
      the Aggression Questionnaire (AQ) are related to treatment response. The subjects
      were 28 aggressive conduct-disordered children (25 males, 3 females), ranging in
      age from 9.8 to 17.0 years (mean age = 12.69 years), who participated in a double
      blind, placebo-controlled study of lithium as a treatment for reducing
      aggression. We used the Predatory-Affective Index of the AQ to classify subjects
      into "predatory" (planned) or "affective" (explosive) subtypes of aggression and
      then related this classification to treatment response. This index did not
      differentiate placebo baseline responders from nonresponders. However, the Index
      did significantly differentiate responders and nonresponders during the
      experimental treatment period, regardless of whether they received lithium or
      placebo. Treatment response was associated with a more affective and less
      predatory subtype of aggression. To the best of our knowledge, this is the first
      study in children to show an association between the aggression subtype and
      treatment response.

PMID- 9564198
TI  - Reliability and validity of the SKAMP rating scale in a laboratory school
      setting.
AB  - In children with attention deficit hyperactivity disorder (ADHD), the effects of
      methylphenidate were investigated in a pharmacodynamic comparison of placebo and
      the standard b.i.d. administration of methylphenidate. In each of these
      conditions, teachers completed ratings in classroom settings at times chosen to
      coincide with expected "peaks" and "troughs" of serum concentrations in the
      b.i.d. condition. Analyses of variance (ANOVAs) revealed the expected differences
      between the two conditions in the laboratory classroom setting using standard
      rating scales (Conners and the IOWA Conners) and a new rating scale (the SKAMP),
      which specifically measures the classroom manifestation of ADHD. The psychometric
      properties of the SKAMP were evaluated by calculating test-retest reliability and
      by calculating correlations with the standard rating scales to establish
      concurrent validity.

PMID- 9564199
TI  - Objective and subjective measures of the pharmacodynamic effects of Adderall in
      the treatment of children with ADHD in a controlled laboratory classroom setting.
AB  - In a randomized double-blind crossover study of children with attention deficit
      hyperactivity disorder (ADHD), the time course effects of four doses of Adderall
      (5, 10, 15, and 20 mg) and an inactive (placebo) control, and an active (Ritalin)
      control were evaluated. A laboratory classroom setting was established in which
      subjective (teacher ratings of deportment and attention) and objective (scores on
      math tests) measurements were taken every 1.5 hours across the day. In addition
      to significant time and dose effects of Adderall, significant time-of-day effects
      were documented in the placebo condition for the subjective measure of deportment
      and objective measures of performance. Regression analyses were used to estimate
      the magnitude of these baseline effects. Correlations across time were used to
      evaluate the test-retest reliability of each measure in the face of these time
      dependent placebo effects. After placebo/time adjustments, within-subject
      correlations between pairs of measures were used to evaluate the validity of the
      math test as a measure of response to stimulant medication.

PMID- 9564200
TI  - Long-term efficacy and safety comparison of sertindole and haloperidol in the
      treatment of schizophrenia. The Sertindole Study Group.
AB  - Sertindole is an atypical antipsychotic that is efficacious in schizophrenia and
      is associated infrequently with extrapyramidal symptoms (EPS). This study
      assessed time to treatment failure with 24 mg/day sertindole or 10 mg/day
      haloperidol in 282 clinically stable neuroleptic-responsive outpatients with
      schizophrenia. During a 5-week transition period, patients were randomized to
      treatment with sertindole or haloperidol; other treatments were gradually
      discontinued. Patients then received treatment through Day 365. Time to treatment
      failure was numerically superior in sertindole-treated patients compared with
      haloperidol-treated patients, although this difference was not statistically
      significant. Sertindole-treated patients, however, remained free of
      hospitalization for exacerbation of schizophrenia and remained medically
      compliant significantly longer than did haloperidol-treated patients. In
      addition, there were significantly fewer reports of EPS in sertindole-treated
      patients and sertindole therapy was generally well tolerated. Patients
      transitioned well from other antipsychotic agents to sertindole. Sertindole
      appears to be an effective long-term treatment for schizophrenia.

PMID- 9564201
TI  - The relationship between negative symptoms of schizophrenia and extrapyramidal
      side effects with haloperidol and olanzapine.
AB  - Atypical neuroleptics present a unique opportunity to examine confounding by
      neuroleptic-induced extrapyramidal symptoms (EPS) in the assessment of negative
      signs of schizophrenia. EPS, such as facial bradykinesia and akinesia, involve
      some of the same response systems and phenomena as emotional display channels.
      EPS are attributed to the blockade of dopamine receptors in the striatum by
      traditional neuroleptics. Newer atypical neuroleptics target primarily mesolimbic
      and mesocortical areas, and receptors for other transmitters such as serotonin.
      Olanzapine has been reported as less likely to cause EPS and may improve some
      negative signs. We investigated the relationship between measures of EPS and
      negative symptoms in patients with schizophrenia treated with haloperidol or
      olanzapine. Patients were rated with the Positive and Negative Syndrome Scale
      (PANSS) and the Simpson-Angus Scale EPS scale. Results show that the two agents
      have comparable efficacy but different safety outcomes. A positive correlation
      between EPS and PANSS negative score was detected in the haloperidol group only.
      Stepwise multiple regression analysis shows that a big proportion of variability
      in PANSS negative symptoms is predicted by EPS in the haloperidol group, but not
      in the olanzapine group, even though EPS increased in patients treated with
      haloperidol but not in olanzapine patients.

PMID- 9564202
TI  - Risperidone: clinical outcome predictors and cost-effectiveness in a naturalistic
      setting.
AB  - Although risperidone seems to be a safe and effective treatment for the
      management of psychotic symptoms, its acquisition cost is considerably higher
      than that of conventional antipsychotics, and its precise role in managing
      psychiatric illnesses has yet to be defined. The purpose of this investigation
      was to examine the relationship of patient demographic variables to therapeutic
      outcomes and to analyze the financial impact of risperidone on the treatment of
      psychotic symptoms. Subjects included in this 2-year, retrospective cohort,
      intent-to-treat analysis were all patients initiated on risperidone therapy at an
      inpatient psychiatric treatment facility. Clinical outcomes were assessed from
      the absolute change in hospitalized days, total number of psychotropic
      medications prescribed, and historic Clinical Global Impression severity scores.
      Logistic regression analysis was conducted to analyze the potential relationship
      to certain demographic variables to therapeutic response. The cost-benefit
      analysis compared the direct treatment costs incurred by the institution before
      and after risperidone initiation. Of the 66 patients originally started on
      risperidone, 57 completed a therapeutic trial. A clinical response was evident in
      54 percent of these patients overall. Logistic regression analysis identified
      previous treatment intolerance and a negative history of substance abuse as
      predictive of therapeutic success with risperidone (p = .0006 and p = .01,
      respectively). Hospitalization rates declined by 43 percent among treatment
      responders and by 1.3 percent among nonresponders resulting in a net annual
      savings of $147,962. Risperidone may be efficacious in many patients who had
      previously failed antipsychotic trials. Patients who had been unable to tolerate
      traditional antipsychotics and those who lacked a documented history of substance
      abuse were uniquely responsive to risperidone treatment. The significant decline
      in hospitalized days that was observed among responsive patients seems to
      indicate that risperidone may be a cost-effective approach to the management of
      psychotic symptoms.

PMID- 9564203
TI  - The effects of risperidone and olanzapine on the indications for clozapine.
AB  - The effects of the availability of risperidone and olanzapine on the indications
      for which clozapine is prescribed (treatment-resistance, treatment-intolerance,
      and/or negative symptoms) were examined for 252 patients with schizophrenia who
      began treatment at our hospital between June 1990 and June 1997. There were no
      statistical differences in the indications for clozapine treatment before and
      after the availability of either risperidone or olanzapine. Furthermore, there
      were no significant differences in the frequencies of the indications in
      subgroups of patients who had previously received a trial with risperidone or
      olanzapine, as compared with the remaining patients. The indications for
      clozapine appear to have been unaffected by the advent of risperidone and
      olanzapine; however, we noted a decrease in the absolute number of patients
      starting clozapine after risperidone became available. More recently, the
      majority of patients referred for treatment with clozapine had received previous
      trials with risperidone or olanzapine.

PMID- 9564204
TI  - Clozapine reduces rehospitalization among schizophrenia patients.
AB  - A number of studies have reported reduced rehospitalization for patients on
      clozapine. This article adds to that literature by mining the clozapine database
      at Hillside Hospital. The sample consisted of 81 schizophrenia patients who
      entered Hillside on a typical neuroleptic and then had their medication changed
      to clozapine. We ascertained the number of inpatient hospitalizations before
      starting clozapine and compared this with the number of hospitalizations after
      starting clozapine. We also followed an age- and gender-matched comparison group
      of other schizophrenia patients who entered Hillside at approximately the same
      time. Results indicate that the mean number of rehospitalizations while on a
      typical neuroleptic was 2.03 (1.93)/year, whereas it was only .56 (.97/year after
      the commencement of clozapine treatment; t(80) = 5.78, p < .001. A 95% confidence
      interval for the superiority of clozapine over standard neuroleptic treatment as
      measured in rehospitalizations/year is (1.0, 2.0). The decrease in
      hospitalization rate of .4 (1.6)/year (pre-index date minus post-index date) for
      the comparison group was also statistically significant [t(80) = 2.3, p < .03];
      the 95% confidence interval for this decrease over time is (.1, .8). The pre-post
      change was much greater for the clozapine patients than comparison patients. A 2
      x 2 repeated measures analysis of variance (ANOVA) contrasting the comparison
      group to the clozapine patients both before and after the index date indicates a
      significant time by group interaction (F(1.80) = 22.35, p < .001), thus
      documenting the greater relative decrease in rehospitalization rate in the
      clozapine group.

PMID- 9564205
TI  - Initial safety, tolerability pharmacodynamics, and pharmacokinetics of CI-1007 in
      patients with schizophrenia.
AB  - CI-1007 is a novel dopamine autoreceptor agonist and partial dopamine D2/D3
      agonist that is currently under development for the treatment of schizophrenia.
      This single-blind, rising, multiple-dose, inpatient bridging study was designed
      to evaluate the safety and tolerability of CI-1007 in consecutive panels of
      patients with schizophrenia. Following a 4-day placebo washout period, 16
      patients (4 per panel) were assigned to receive one of four fixed-dosage regimens
      of CI-1007 (5, 10, 15, or 20 mg q12h for 9 doses). CI-1007 was generally well
      tolerated over the dose range evaluated. Adverse events, including mild to
      moderate sporadic orthostatic hypotension and/or nausea and vomiting, were most
      commonly observed after the initial drug dose and decreased after repeated
      dosing. Serum concentrations of growth hormone (GH) increased following the
      administration of CI-1007, confirming its central dopamine agonist activity.
      Changes in serum prolactin were not related to dose. The pharmacokinetics of CI
      1007 and its active metabolite appear linearly related to dose. The results of
      this study suggest that patients with schizophrenia tolerate slightly higher
      initial doses of CI-1007 than do healthy subjects.

PMID- 9564206
TI  - Pharmacologic treatment of alcoholics with collateral depression: issues and
      future directions.
AB  - Patients in treatment for alcoholism often suffer collateral depressive
      disorders. Fortunately, recent advances in medications development may
      significantly improve outcome for this population, but there remain several
      concerns about the clinical use of pharmacologic agents in these cases. These
      concerns are discussed, as are research findings that bear on them. Directions
      for future research are also identified.

PMID- 9564207
TI  - Naltrexone utility in depressed alcoholics.
AB  - The aim of this open-label pilot study was to evaluate the utility of naltrexone
      (50 mg per day) in decreasing alcohol use and to examine its impact on depressive
      symptoms among depressed alcoholics who have failed to abstain from alcohol use
      despite treatment with a selective serotonin reuptake inhibitor (SSRI). Fourteen
      ambulatory care patients, aged 18 to 65 years, with DSM-III-R comorbid diagnoses
      of alcohol dependence and major depressive disorder, who failed to abstain
      despite treatment with an antidepressant medication were enrolled in the study.
      Patients were followed for 12 weeks with weekly assessment of drinking behavior,
      depressive symptoms, functioning, alcohol craving, and side effects. The results
      of this study indicated a significant decrease in alcohol use and in urges to
      drink alcohol in the presence of the usual triggers. There was also a trend
      suggesting improvement in depressive symptoms and overall functioning. Naltrexone
      was well tolerated, with mild side effects reported at the onset of treatment.

PMID- 9564209
TI  - Reframing the quest: health for all.

PMID- 9564208
TI  - Fluoxetine versus placebo in depressed alcoholic cocaine abusers.
AB  - To date, few double-blind, placebo-controlled studies with any selective
      serotonin reuptake inhibitor (SSRI) antidepressant in pure cocaine abusers or in
      cocaine abusers with comorbid disorders have been reported. In this study, 17
      patients with DSM-III-R diagnoses of major depressive disorder, alcohol
      dependence, and cocaine abuse were included along with 34 non-cocaine-abusing
      depressed alcoholics in a pharmacotherapy trial involving the SSRI antidepressant
      fluoxetine. All 51 patients participated in a double-blind, parallel group study
      of fluoxetine versus placebo in depressed alcoholics. The principal focus of this
      article is the one-third of the depressed alcoholics who also abused cocaine and
      how the treatment response of those 17 patients compared with that of the 34
      depressed alcoholics who did not abuse cocaine. During the study, no significant
      difference in treatment outcome was noted between the fluoxetine group (N = 8)
      and the placebo group (N = 9) for cocaine use, alcohol use, or depressive
      symptoms. In addition, no significant within-group improvement was noted for any
      of these outcome variables in either of the two treatment groups. Indeed, across
      the combined sample of 17 depressed alcoholic cocaine abusers, the mean Beck
      Depression Inventory (BDI) score worsened slightly from 19 to 21 during the
      course of the study, and 71 percent of the patients continued to complain of
      suicidal ideations at the end of the study. The 17 cocaine-abusing depressed
      alcoholics showed a significantly worse outcome than the 34 non-cocaine abusing
      depressed alcoholics on the 24-item Hamilton Rating Scale for Depression (HAM-D)
      and BDI depression scales and on multiple measures of alcohol consumption. These
      findings suggest that comorbid cocaine abuse acts as a robust predictor of poor
      outcome for the drinking and the depressive symptoms of depressed alcoholics.

PMID- 9564210
TI  - In her own words: the story of Doris R. Schwartz, R.N., M.S., FAAN, public health
      nurse.

PMID- 9564211
TI  - An Arabic language version of the health promotion lifestyle profile.
AB  - The purpose of this study was to assess the validity and reliability of an Arabic
      version of the Health-Promoting Lifestyle Profile instrument in Jordan, whose
      society and culture differ from that of North America, where the instrument was
      developed. The instrument was translated into Arabic, back-translated, and pilot
      tested to ascertain cultural sensitivity. The Arabic version was then evaluated
      using a convenience sample of 950 adults in the northern part of Jordan using a
      principal components factor analysis. The order of factors was not entirely
      identical to those isolated previously during the psychometric assessment of the
      English language version. Only the structure of three factors--self
      actualization, health responsibility--and exercise were the same as those
      obtained in the English version. The forced, six factor solution explained only
      39.3% of the variance in the measure. The alpha reliability coefficients were
      0.89 for the total scale and ranged from 0.85 to 0.60 for the subscales. It was
      concluded that the Arabic version of the Health-Promoting Lifestyle Profile has
      demonstrated initial reliability and validity. Further testing is recommended.

PMID- 9564213
TI  - The importance of the health education program environment for pregnant and
      parenting teens.
AB  - Teenage Pregnancy is recognized as one of this country's most critical social
      issues. Each year, one out of ten females aged 15 to 19 becomes pregnant. In
      addition, there are a number of documented complications and consequences for the
      pregnant teenagers, their children, families and society. In response a number of
      health education programs have been developed to meet the myriad needs of this
      aggregate. Unfortunately, most of this cohort do not participate in these health
      education programs. This study, a part of a larger study, was conducted to
      identify the health education program elements most important to attract and
      sustain the participation of pregnant and parenting teens in a health education
      program. The sociodemographics of the pregnant and parenting teens were
      identified and linked to program elements. Since sociodemographics are often the
      first information known about a target group, linking these demographics to
      health education program elements has implications for program development and
      marketing. An exploratory survey methodology was used in this study and data were
      analyzed by measures of central tendency, dispersion, and analysis of variance to
      understand better the relationship between sociodemographic characteristics and
      importance of the health education program environment for pregnant and parenting
      teens.

PMID- 9564212
TI  - The effects of nursing case management on the utilization of prenatal care by
      Mexican-Americans in rural Oregon.
AB  - This quasi-experimental, retrospective study used birth certificate and medical
      record data to evaluate the effectiveness of the Rural Oregon Minority Prenatal
      Program (ROMPP) in improving patterns of prenatal care utilization by rural
      dwelling, low-income, Mexican-American women at risk of poor pregnancy outcomes.
      The ROMPP intervention provided nursing case management services and peer
      outreach to pregnant Mexican-American women in a rural Oregon community. The
      intervention group had more prenatal visits in months 2, 3, 4, 5, 6, and 7 than
      the comparison group (P < 0.05). The intervention group had a similar number of
      emergency room (ER) visits, but had more respiratory diagnoses and fewer urinary
      tract infections. ROMPP women had more inpatient admissions and longer lengths of
      stay. No differences were found in the initiation of prenatal care or the total
      number of prenatal care visits, nor in the timing of screening serum glucose
      tests. The intervention should be expanded to address the persistent attitudinal,
      financial, transportation and language barriers to adequate prenatal care. Nurses
      should increase their cultural competency and sharpen their clinical focus on
      advocacy, marketing, facilitation of relationships between community groups, and
      community organizing.

PMID- 9564214
TI  - Collaboration between schools of nursing and local education agencies to provide
      health care services to pre-kindergarten through twelfth grade students: elements
      of cooperative agreements.
AB  - Establishing cooperative relationships between schools of nursing and local
      education agencies for the delivery of health care services to children from pre
      school through the twelfth grade is a process all too often characterized by
      numerous legal, insurance, and administrative roadblocks. While nursing faculty
      and their students may wish to cooperate with professional educators and their
      students to enhance the health care of the children, there are obstacles. Both
      institutions are represented by attorneys, insurance companies and others who
      must attend to aspects of the process other than direct health care delivery. A
      model for joint planning and a list of elements of effective agreements are
      offered as a way of engaging all parties in a constructive and useful process of
      collaboration.

PMID- 9564215
TI  - Nursing research on the health of low-income women.
AB  - The purpose of this paper is to describe the scope of published nursing research
      on the health of low-income women. Williams' (1990) model of the relationship
      between socioeconomic status and health was used as a framework for the analysis.
      This model includes three major components: Medical Care, Psychosocial Factors,
      and Health Outcomes. There is a body of published nursing research that addresses
      a range of health issues of low-income women. Our search of English language
      literature published between 1989 and 1995 retrieved 49 articles that met the
      inclusion criteria. Most of the nursing studies examined a portion of Williams'
      model but did not address multiple components. The most frequently addressed
      component was Psychosocial Factors, particularly health practices, stress and
      coping, and social ties. Williams' model was an effective framework to classify
      nursing research. Results of our analysis suggest that further research is needed
      on the pathways by which low income influences health and on the effectiveness of
      nursing interventions.

PMID- 9564216
TI  - Data sources to estimate local area supply and demand for nurses.
AB  - This paper examines existing data sources that can be used to estimate the local
      supply and demand for registered nurses (RNs). An analysis of the strengths and
      weaknesses of these data is provided.

PMID- 9564217
TI  - Interorganizational collaboration: a cautionary note for tribal health nurses.
AB  - As the Indian Health Service restructures and more Indian tribes assume control
      for their health care services, more collaborative initiatives between Indian
      tribal health and other organizations may be anticipated. This paper addresses
      the topic of interorganizational collaboration and tribal health care. There are
      unique issues related to Indian tribal healthcare, and this paper provides a
      cautionary note to public health nurses who work with and for Indian tribes.
      Interorganizational collaboration and tribal health care will of be interest not
      only to the public health nurses working for a tribe, but also to the county and
      state public health nurses who may be entering into a collaborative effort with a
      tribal health care agency.

PMID- 9564218
TI  - Depression, physical health impairment and service use among older adults.
AB  - The purposes of this study were: (1) to compare service use and need among 80
      community-dwelling older adults (55 women and 25 men); and (2) to examine the
      influence of depression on service use and need. Participants were divided into
      three groups based on their depression scores (no depression, mild depression,
      severe depression) and compared on a wide range of services. (e.g., medical
      services, social/recreational, transportation) typically used by older adults.
      There were no significant differences among the three groups for demographic
      characteristics and chronic illness types, but there were significant differences
      for physical health impairment (PHI). When controlling for PHI, significant
      differences were found among the groups for mental health services, psychotropic
      medications, number of sick days, hospitalizations, home help, frequency of
      transportation, social/recreational services, and sports-related activities.
      Mildly and severely depressed older adults used and needed more medical services
      than did their non-depressed cohorts, but used less of other types of services
      (e.g., social/recreational services). Depression was a significant predictor of
      social/recreational service use, and for need of mental health services,
      psychotropic medications, financial assistance, and assessment and referral
      services. A consistent pattern was found of depression influencing service use
      and need.

PMID- 9564219
TI  - Home care utilization by congestive heart failure patients: a pilot study.
AB  - Home health care costs have increased more than any other health care service
      covered by Medicare, and new methods of payment by Medicare are being introduced.
      A prospective payment system would replace the per visit rate now paid to home
      care agencies by Medicare. In order to remain viable under a new payment system,
      home health care agencies will need to be efficient in the delivery of home care
      services and still demonstrate effective patient care. The intent of this
      descriptive study was to determine norms of resource utilization for the
      congestive heart failure (CHF) patients admitted and discharged from a not-for
      profit home health agency (HHA). Forty agency records were retrospectively
      reviewed using the Resource Utilization Inventory to collect the characteristics
      and resource utilization of the sample group. The CHF patients were older than
      most home care clients and had chronic health problems. Because of these chronic
      health problems, over half of the study population had caregivers so that the
      clients could remain in their own homes. Most clients clearly demonstrated the
      need for skilled nursing or home health aide visits after being hospitalized for
      an acute CHF episode. Less than half of the study group were discharged form the
      HHA as improved, and frequently were discharged to another healthcare facility.
      These results provide a beginning direction for profiling the CHF patient's
      consumption of resources for setting prospective reimbursement rates.

PMID- 9564220
TI  - [Image of the month. Pheochromocytoma demonstrated by positron emission
      tomography using carbon-11 labeled meta-hydroxyephedrine].

PMID- 9564221
TI  - [How I treat a diabetes type 2 patient: the DREAM project for better general
      practitioner-specialist collaboration. Diabetes Reinforcement of Adequate
      Management].
AB  - Type 2 diabetes is an important public health problem because of its high
      prevalence and morbidity rate which both are associated with a considerable
      social and human cost. The general practitioner should play a central role in the
      management of patients with type 2 diabetes and try to meet the therapeutic
      objectives. Main goals include reinforcement of early diagnosis, by a better
      screening of individuals at risk for type 2 diabetes, achievement of a good
      glycaemic control, through an optimized antidiabetic treatment, correction of
      associated risk factors as well as detection and treatment of disease
      complications. DREAM ("Diabetes Reinforcement of Adequate Management") is a pilot
      project which started in Liege area end 1997 for at least 2 years. It aims at
      improving the management of type 2 diabetic patients through a better free
      collaboration between general practitioners and diabetologists and the adhesion
      to an optimized therapeutic strategy. This ambitious project benefits from the
      valuable support of three pharmaceutical companies.

PMID- 9564222
TI  - [Clinical case of the month. Apropos of a case of adrenal ganglioneuroma: the
      incidentaloma].
AB  - We present a case of adrenal ganglioneuroma discovered during a gastric
      exploration. We review and discuss the recent literature about "incidentaloma".
      We propose a reflexion about the investigation of these masses.

PMID- 9564223
TI  - [Atopic dermatitis].
AB  - For the past decades, the prevalence of atopic dermatitis is on the rise. Three
      phases of the disease are recognized according to the age of the patient, either
      in the newborn age, in infancy or after puberty. A partial enzymatic defect in
      delta-6 desaturase has been reported. Such metabolic anomaly would be responsible
      for the alterations in both the skin barrier function and in the Th2 inflammatory
      reactions in part mediated through IgE. Some microorganisms colonizing the skin
      play an important causal role in the clinical exacerbations. The influence of
      food allergy on atopic dermatitis remains obscure and often unconvincing. By
      contrast, irritant and allergic challenges from the environment exhibit an
      undisputable worsening effect. The prevention relies on the eviction of
      predisposing factors and is favourably influenced by emollients specifically
      designed for atopic dermatitis. A food supplementation in alpha-linoleic acid and
      some specific chinese herbal remedies might well be useful. The treatment relies
      primarily on topical applications of corticoids. Puva-therapy, UVB phototherapy
      and immunomodulation by cyclosporine are indicated for difficult cases.

PMID- 9564224
TI  - [Minimal cardiac surgery].
AB  - In general surgery, the aim of new techniques is to reduce the length of the skin
      incisions and/or to use endoscopic or laparoscopic instruments. The cardiac
      surgery makes not an exception. During the last two years, the material and the
      techniques are following a progressive evolution. Concerning the cardiac surgery
      of the adult, three techniques which are the mini-incision or thoracotomy and the
      surgery of the port-access are in full evolution. We describe the advantages and
      disadvantages.

PMID- 9564225
TI  - [Innovative new approaches in pharmacology].
AB  - After a brief recall of the molecular bases of the pharmacological actions, the
      two main ways of discovery of new drugs are described. On the one hand, the
      "deductive" approach starts with the elucidation of the pathogenic mechanisms and
      leads to selective drug designs for the appropriate receptors. The recent
      contributions of the molecular biology in this way are illustrated by some
      examples: "knock out" mice for the study of gene functions, discovery of new
      antibiotics thanks to genomic sequencing of bacteria, new pathogenic concepts
      about inflammation... On the other hand, the empirical approach is now grounded
      on two performant methods: High Throughput Screening and Combinatorial Chemistry
      which together have already given practical results. It is obvious that these two
      approaches are not opposite, but complementary.

PMID- 9564226
TI  - [Intraperitoneal chemotherapy in colorectal cancer: from the laboratory to the
      clinic].
AB  - Some patients operated of a colo-rectal cancer can be selected to receive a post
      operative adjuvant chemotherapy to decrease the risk of recurrence. The authors
      report the results of experimental works on intraperitoneal chemotherapy (IPC).
      At the laboratory, they showed that this option significantly reduced the risk of
      recurrences in the most frequent sites of colo-rectal cancer recurrences: liver,
      lymph nodes, peritoneum and the surgical site. Moreover, the survival of the
      treated animals was significantly prolonged compared to the controls. In human,
      they proved the feasibility of a intraperitoneal chemotherapy managed into the
      immediate post-operative period. Low morbidity, null mortality and the
      interesting preliminary carcinological results suggest the interest of such an
      option which could be confirmed by a randomized multi-centric study currently in
      preparation.

PMID- 9564227
TI  - [Cardiac assistance using transformed striated skeletal muscle: cardiomyoplasty].
AB  - The biomechanical potential of transformed skeletal muscle used for
      cardiocirculatory assistance is the keystone of this surgical concept. This
      underscores the necessity to modulate type II to type I transformation to premise
      the muscle bulk, shortening velocity, and, therefore, power. It is only if an
      efficient autologous engine is available that optimal surgical configuration
      (i.e. aortomyoplasty) will provide active cardiocirculatory support.

PMID- 9564229
TI  - [The current status of organ transplantation: the role of xenotransplantation?].
AB  - In the last few years, transplantation was an area of intense research activity.
      However, there is a worldwide shortage of donor organs for clinical
      transplantations. Currently, interest in xenotransplantation research is growing
      not only because of the increased demand for organs but also because of advances
      in molecular biology techniques that make possible the genetic or immunological
      manipulations of the animal donor rather than the human recipient. The better
      definitions of the mechanisms responsible for xenograft rejection should
      facilitate appropriate therapeutic strategies for long xenograft survival.

PMID- 9564228
TI  - [From the study of biochemical changes in ischemic and reperfused skeletal muscle
      to the controlled reperfusion of limbs in patients with acute severe ischemia].
AB  - The reperfusion of a limb which has been submitted to a severe and prolonged
      period of ischemia may be followed by dramatic local and systemic complications.
      The results of several experimental studies have given insights on the
      biochemical and physiopathological alterations occurring in the ischemic and
      reperfused skeletal muscle. Therefore the technique of the controlled limb
      reperfusion has been developed. we present the results obtained in two patients
      with this technique. Two patients were admitted for a limb-threatening ischemia
      consecutive to embolism. After removal of the thrombi with a Fogarty's catheter
      and before reperfusion with the normal blood, a controlled limb reperfusion was
      performed by mixing the systemic blood with a crystalloid solution in order to
      obtain a hyperosmolar, hypocalcemic, alcalotic and substrate-enriched (aspartate
      and glutamate) reperfusate. This reperfusate was infused during 30 min with a
      roller pump into the deep and superficial femoral arteries. The delivery
      conditions (temperature, flow and reinjection pressure) were closely monitored.
      In both cases, no post-operative complication was observed and the pedal pulses
      were restored after the operation. Complete recovery of the motor and sensitive
      functions were observed and the patient were discharged at the 10th post
      operative day.

PMID- 9564230
TI  - [How I study hypertriglyceridemia].
AB  - The strategy for the diagnosis of hypertriglyceridaemia comprises three
      successive steps. First, the physician should confirm the biological abnormality
      by at least one additional blood sample taken after an overnight fast; recent
      data, however, suggest that postprandial hypertriglyceridaemia may also represent
      a cardiovascular risk factor. Second, the phenotype of hypertriglyceridaemia
      should be considered as either isolated high triglyceride levels or
      hypertriglyceridaemia combined with hypercholesterolemia may be present; the
      combination of hypertriglyceridaemia with a low HDL cholesterol concentration or
      its association with the metabolic or insulin resistance syndrome should also be
      investigated. Third, all should be done in order to find the etiology of the
      hypertriglyceridaemia (by determining its genetic or nutritional origin, by
      excluding possible underlying pathologies, by looking for drugs able to increase
      serum triglyceride levels). These various steps should help the physician to take
      the final decision of treating one particular patient as well as to chose the
      most appropriate, nutritional or pharmacological, treatment.

PMID- 9564231
TI  - [Pharma-Clinics. The drug of the month. Venlafaxine (Efexor)].
AB  - Venlafaxine (Efexor) is the first representative of a new class of
      antidepressants: serotonin noradrenaline reuptake inhibitors. Its usual dose is
      75 mg/d in two intakes but can be progressively increased until a maximal daily
      dose of 375 mg/d in severe or resistant depression, particularly among
      inpatients. The efficacy of venlafaxine is at least equivalent to reference
      antidepressants. At high doses, venlafaxine could even exhibit a better efficacy
      and a shorter latency than current compounds. Its profile of side-effects is
      quite similar to selective serotonin reuptake inhibitors with mainly nausea, with
      the exception if an increase in blood pressure which can appear at high doses. In
      total, venlafaxine represents an interesting innovation in the pharmacological
      treatment of depression.

PMID- 9564232
TI  - [Pharma-Clinics. The drug of the month. Adapalene (Differin gel)].
AB  - Adapalene is a new topical retinoid derived from naphthoic acid with a selective
      effect on the epidermis. It is indicated for treatment of acne vulgaris, alone or
      with other antiacneic topicals. It displays comedolytic and anti-inflammatory
      activities. The only frequent adverse event is a mild skin irritation during the
      first two weeks of treatment.

PMID- 9564233
TI  - Families and children's chronic conditions: knowledge development and
      methodological considerations.
AB  - The complexity of studying families has been a deterrent in the development of
      knowledge about families as the unit of care. When chronicity in childhood is
      combined with family study, research and theory development is particularly
      challenging. Although publication in the field of chronic illness in childhood
      has been quite prolific, there are few comprehensive, recognizably organized ways
      to think about providing care for the family as a whole. This is profoundly
      important as increasing responsibility of day-to-day care for children with long
      term health conditions shifts to the family and to community-based care. This
      paper presents a synthesis of what is known about families in health care when
      one member is a child with a long-term health concern, identifies gaps in
      knowledge that potentially compromise optimal health care delivery, and suggests
      methods for expanding and deepening our understanding so that we might improve
      the quality of our efforts to assist families that live with a child with a
      chronic condition.

PMID- 9564234
TI  - The use of seclusion in psychiatry: a literature review.
AB  - This article reports on a literature review of the practice of seclusion in
      psychiatric inpatient facilities. Attention is paid to the moral debate on
      seclusion. Most publications consider seclusion as a necessary intervention to
      manage problem behavior. The first part of the article deals with definitional
      aspects leading toward concept clarification. The review shows differences in
      definitional aspects, motives for seclusion, hospital characteristics, and
      patient characteristics. Data on frequency, incidence, and duration appear to be
      widely divergent. The experiences of patients who have been secluded are mostly
      negative, but positive reactions are also reported. In the publications of the
      last decade, there is emphasis on the contribution of hospital characteristics to
      trends in use of seclusion. Finally, it is concluded that seclusion is an
      effective way to manage (potentially) dangerous behavior and that seclusion is an
      intervention that may create therapeutic possibilities for care.

PMID- 9564236
TI  - [Autologous cartilage transplantation--the future in arthrosis therapy?].

PMID- 9564235
TI  - The comforting interaction: developing a model of nurse-patient relationship.
AB  - In this article we argue that the separate literatures on the nurse-patient
      interaction and the nurse-patient relationship artificially fragment a unified
      process, and a model incorporating both interaction and relationship is
      critically needed. The Comforting Interaction-Relationship Model, in which the
      nurse-patient interaction is proposed as a means for the nurse and the patient to
      negotiate and establish a desired therapeutic relationship is presented. Nursing
      actions are described as three interrelated levels: 1) comforting strategies, or
      separate discrete actions which together form nurses' styles of care, 2) styles
      of care, or sets of comforting strategies, and 3) patterns of relating, or
      normative, professional behaviors. These three processes are provided in response
      to patient signals of distress, indices of discomfort, and patterns of relating
      that form patient actions. It is through this interaction of nursing actions and
      patient actions that the nurse-patient relationship is negotiated. This model is
      patient-led, dynamic, interactive, and context dependent. Even though the model
      is driven by the patient's behavioral state, actions, and reactions, both the
      nurse and the patient maintain control--the nurse selects the strategy or style
      to be used, and the patient, in negotiating, relinquishing, and accepting care,
      maintains control. Suggestions for future research are presented.

PMID- 9564237
TI  - [Sensitivity of bacteria to therapeutic drugs (Zurich 1996)].
AB  - This paper describes the frequency of susceptibility of Gram-negative and Gram
      positive bacteria against antibacterial agents. The data are based on all
      susceptibility tests performed in 1996 at the Department of Medical Microbiology
      of the University of Zurich and at the private medical laboratory "medica" in
      Zurich. The evaluation of the results from 1975 to 1996 shows that
      susceptibilities against the antimicrobial agents tested have not changed
      markedly in this period with few exceptions. The tables may be a help for the
      physician in his decision for a "calculated chemotherapy" of bacterial
      infections.

PMID- 9564238
TI  - [Drug-induced discoloration of the teeth and gingiva].
AB  - For this article all cases of suspected drug-induced discolouration of teeth and
      gingiva reported between 1.1.1989 and 31.5.1997 have been collected. As far as
      documented all discolourations were reversible and represented exclusively
      undesired but not serious adverse drug effects. In the literature such events are
      usually not mentioned. Thus, sense and intention of this work is to draw
      attention to certain adverse effects that are hitherto not well known.

PMID- 9564239
TI  - [Victims of violence: importance of medical testimony for the practitioner].
AB  - Physicians may be asked to provide care to victims of violence. Adequate
      diagnostic and therapeutic management must be provided. Establishing a detailed
      medical testimony can substantially influence the judiciary or administrative
      procedure's outcome. This paper provides guidelines for writing a medical
      testimony and describes the criteria that physicians need to consider in order to
      serve at best the interests of their patient within a mutually trustful
      relationship.

PMID- 9564240
TI  - [Do antibiotics improve acute maxillary sinusitis?].

PMID- 9564241
TI  - [62-year-old patient with chronic pain in the area of the carotid arteries].
AB  - A 62-year-old woman was admitted for investigation of severe chronic recurring
      lateral neck pain radiating to the face with predilection for the right side for
      30 years. The main clinical finding was tenderness of the extracranial carotid
      arteries (Fay's sign). The ultrasound-investigation of the neck- and brain
      arteries did not reveal any pathological findings. The laboratory investigations
      provided no evidence of inflammation but revealed primary hyperparathyreoidism.
      Lateral radiating neck pain with tenderness of the carotid arteries are
      summarized under the term carotidynia, provided no pathological changes of the
      arteries are found. Whether carotidynia actually is an entity is uncertain.
      Nevertheless it is suggested to maintain the term for a carotid pain-syndrome
      whenever dangerous pathological conditions of the carotid arteries have been
      ruled out. In acute varieties which normally respond to NSAID a infectious
      aetiology has been postulated. Chronic carotidynias are probably a variety of
      migraine and tend to resolve with an antimigraineous therapy. There do not exist
      any reports on the coincidence of carotidynia and hyperparathyreoidism. After an
      attempt for parathyreoidectomy which failed because of extensive local scaring
      the patient was persistently free of pain without any obvious pathophysiological
      explanation for this fact.

PMID- 9564242
TI  - [Abdominal typhus].

PMID- 9564244
TI  - Ethics and managed care.

PMID- 9564243
TI  - Navigating the morass.

PMID- 9564245
TI  - How the new Stark II regulations affect group practices.

PMID- 9564246
TI  - The promise and the peril.
AB  - The medicare population represents the most important group of covered lives to
      most providers. Medicare is now pushing seniors to join risk-based plans, and is
      encouraging providers to form PSOs to contract directly with Medicare for risk
      based contracts. By eliminating the commercial HMOs as the middlemen, PSOs can
      not only control their own destiny as providers, they can retain the risk
      'profit' in the community for enhanced services or higher payments to providers.
      To be successful, however, PSOs must have in place the key elements to manage the
      organization in a managed care environment. While the task of creating a PSO can
      appear daunting and the risk can be real and substantial, every provider
      organization should examine the potential of starting or joining a PSO. The
      greatest risk could be the risk of doing nothing, which could lead to loss of
      control of the Medicare population, decreased utilization, declining payment for
      services, the loss of patients being directed to other providers, and the loss of
      the risk premium from Medicare capitation.

PMID- 9564247
TI  - Apparent complication of common procedure.

PMID- 9564248
TI  - Liver biopsy-associated hemobilia treated conservatively.

PMID- 9564249
TI  - Paradoxical embolism and a patent foramen ovale.
AB  - Patients who sustain an unexplained stroke or peripheral ischemic event should be
      examined for paradoxical embolism via right-to-left shunting. The confirmation of
      a patent foramen ovale by echocardiography is simple and noninvasive, and should
      suggest the possibility of a right-sided embolic source. Unrecognized right-to
      left shunting that allows paradoxical embolism may be more frequent than
      generally recognized.

PMID- 9564250
TI  - Geriatric evaluation is a useful adjunct to traditional medical care of the frail
      older patient.
AB  - GEMU evaluation is most helpful in complicated cases where frail elderly patients
      appear likely to require custodial nursing home care in the near future. The best
      results and most significant reductions in subsequent mortality have occurred in
      less ill or more recently debilitated elders with a reasonable chance of
      returning to modified self-care in the home or in assisted living situations.
      Adapting these principles in an effective, cost-efficient manner for outpatient
      care is the focus of the majority of current investigations of CGA/GEM.
      Unfortunately, this option will not be universally available even after the
      proper parameters for its use are determined. Furthermore, better geriatric
      assessment and earlier intervention could logically prevent or forestall the
      patient's functional decline, dependency, and the need for placement. Toward that
      goal, the reader is referred to a practical guide to efficient outpatient
      geriatric assessment for general internists and other primary care providers,
      published by Dr. D.B. Reuben in 1996. A number of questionnaires and rapid
      screening techniques are included, which make these assessments less cumbersome
      and thus feasible in this era of austere Medicare reimbursement. However, when
      managing the care of outpatients with multiple impediments to independent living
      or hospitalized patients who are partially dependent upon others and are likely
      to require nursing home placement at (or shortly after) discharge, careful
      consideration should be given to referral for formal GEM, even if travel to a
      metropolitan area is required.

PMID- 9564251
TI  - Keeping mothers and babies healthy in Tennessee.

PMID- 9564252
TI  - A 21-year-old man with mental status changes.

PMID- 9564253
TI  - On the right track. Riding the Professionalism Express.

PMID- 9564254
TI  - MedBytes.

PMID- 9564255
TI  - Forum on ethics.

PMID- 9564256
TI  - The "Texas bill".

PMID- 9564257
TI  - Cow town showdown.

PMID- 9564258
TI  - Rounding up the metroplex health care herd.

PMID- 9564259
TI  - Patients need protection under managed care.

PMID- 9564260
TI  - Fighting evil.

PMID- 9564261
TI  - Swimming upstream.

PMID- 9564262
TI  - Jungle medicine.

PMID- 9564263
TI  - A PCR-based diagnostic test for fucosidosis in English springer spaniels.

PMID- 9564264
TI  - What is the function of the guttural pouches: selective brain cooling?
      Augmentation of swallowing? Still to be defined?

PMID- 9564265
TI  - Oral fluids for equine diarrhoea: an underutilized treatment for a costly
      disease?

PMID- 9564266
TI  - Feline immunodeficiency virus infection: an overview.
AB  - In 1987, Pedersen et al. (1987) reported the isolation of a T-lymphotropic virus
      possessing the characteristics of a lentivirus from pet cats in Davis,
      California. From the first report onwards, it was evident that in causing an
      acquired immunodeficiency syndrome in cats, the virus was of substantial
      veterinary importance. It shares many physical and biochemical properties with
      human immunodeficiency virus (HIV), and was therefore named feline
      immunodeficiency virus (FIV). This article reviews recent knowledge of the
      aetiology, epidemiology, pathogenesis, clinical signs, diagnosis, prevention, and
      treatment options of FIV infection.

PMID- 9564267
TI  - A preliminary study on the role of the equine guttural pouches in selective brain
      cooling.
AB  - The equine guttural pouch is a large, air-filled diverticulum of the auditory
      tube whose function is not clear. Since the horse does not possess a known, well
      developed brain-cooling mechanism that could satisfy cerebral thermoregulatory
      demands, an hypothesis is proposed that respiratory air enters the guttural
      pouches, when needed, to ventilate and cool the internal carotid arteries (ICA).
      Experiments were initially carried out on nine cadavers, where blood flow was
      mimicked with warmed saline propelled by peristaltic pumps. Subsequent
      experiments were conducted on an anaesthetized horse where the guttural pouch was
      ventilated and ICA temperatures were measured. Results showed that whenever the
      guttural pouch was ventilated with cooled or warmed environmental air, or warmed
      100% humidified air, temperatures within the ICA dropped significantly in
      cadavers (0.4-5 degrees C) and in the anaesthetized horse (1-3 degrees C),
      depending on conditions. Simulated respiration trials also resulted in ICA
      temperature drops of 0.9-2.3 degrees C in two of five cadavers tested, indicating
      that the wide 3-5 cm pharyngeal orifices of the guttural pouches have the
      capacity to allow enough respiratory air to ventilate the pouch. Despite the fact
      that a single, unbranching 13 cm portion of the ICA is exposed on the wall of
      each guttural pouch, the results of this investigation suggest that during heavy
      exercise, horses could utilize their guttural pouches to cool ICA blood destined
      for the brain.

PMID- 9564268
TI  - Induced diarrhoea in horses. Part 1: Fluid and electrolyte balance.
AB  - Sodium, potassium and water balance, and measurements of acid-base status,
      haematocrit, packed cell volume and plasma total protein, were studied in four
      adult standardbred geldings following castor oil induced diarrhoea. Castor oil (2
      mL kg-1) administration resulted in signs consistent with mild to moderate acute
      colitis. The total (combined faecal and urinary losses) losses of sodium and
      potassium ions were 2169 and 2864 mmol, respectively. Faeces constituted the
      major route for sodium loss, while urine was the major route for potassium loss
      at all times. Faecal dry matter potassium concentration did not vary
      significantly at any stage. Faecal dry matter sodium concentration increased
      significantly, coinciding with the onset of clinical diarrhoea. Faecal water loss
      increased significantly from 2.15 +/- 0.44 mL kg-1 h-1 to 5.15 +/- 0.92 mL kg-1 h
      1 while clinical diarrhoea was observed. While plasma volume (PV) did not vary
      significantly in this study, there was a trend for PV to decrease while horses
      were clinically dehydrated.

PMID- 9564269
TI  - Induced diarrhoea in horses. Part 2: Response to administration of an oral
      rehydration solution.
AB  - Hydration status, electrolyte balance and acid-base balance were studied in four
      adult standardbred geldings with castor oil-induced diarrhoea. The horses
      received an oral rehydration solution (ORS) at a point when signs consistent with
      mild decreases in effective circulating fluid volume were first detected. Within
      1.5 h of ORS administration, all horses exhibited a significant metabolic
      acidosis. At this time, mean values for venous blood pH, [HCO3], and standard
      base excess were 7.264 +/- 0.011, 17.7 +/- 0.3 mmol L-1, and -8.2 +/- 0.4 mmol L
      1, respectively. Throughout the duration of the study, plasma volume did not
      change significantly, despite a decreasing trend, which tended to recover towards
      normal values 8 h after administration of the ORS. Signs of abdominal discomfort
      were observed in all horses following the last of three doses of ORS (8-10 L)
      administered at 30 min intervals. Faecal fluid sodium concentration increased
      significantly with diarrhoea, and reached values fourfold those in normal horses,
      while faecal dry matter sodium concentration increased exponentially following
      the onset of clinical signs. Despite this increase in sodium concentration,
      faecal fluid remained hypotonic at all stages. Our findings suggest that, while
      ORS can help restore systemic fluid balance, several factors influence their
      effectiveness. Two likely factors identified in this study were the ionic
      composition of the ORS as well as the rate of administration. We concluded that
      the electrolyte composition of current ORS may not be ideal to treat diarrhoea in
      horses and that administration of 8-10 of ORS every 30 min via nasogastric tube
      may result in too rapid small intestinal transit to allow sufficient time for
      absorption.

PMID- 9564270
TI  - Assessment of immunization response to canine distemper virus vaccination in
      puppies using a clinic-based enzyme-linked immunosorbant assay.
AB  - To study the response to vaccination, an enzyme-linked immunosorbant assay
      (ELISA) immunoblot method was developed and tested to assay canine distemper
      virus (CDV) IgG antibody in puppies and compared to a standard virus
      neutralization (VN) test (r2 = 0.748). Ten litters of four puppies each were used
      in a vaccination study. Seventy-six percent of vaccinated puppies immunized with
      a modified live vaccine were successfully protected against CDV at 6 weeks of
      age. One puppy remained seronegative after vaccination at 6 and 9 weeks of age.
      This is the first report of vaccination responses of puppies to CDV using an in
      clinic test kit based on solid-phase immunoassay technology.

PMID- 9564271
TI  - In vitro effect of glucocorticoids on phagocytic function of sheep alveolar
      macrophages.
AB  - The potentiation of infection is a recognized adverse effect of steroids. This
      study examined the in vitro effect of glucocorticoids on sheep alveolar
      macrophage phagocytic function, an essential means of cellular defence in the
      lungs, by evaluating the phagocytosis of zymosan particles after 30 min of
      contact between alveolar macrophages and steroids. Hydrocortisone, dexamethasone
      phosphate and methylprednisolone significantly reduced the phagocytic capability
      of sheep alveolar macrophages, but the effects of dexamethasone isonicotinate,
      prednisolone and flumethasone were less marked.

PMID- 9564272
TI  - A comparison of methods used in species identification of coagulase-negative
      staphylococci isolated from the milk of sheep.
AB  - Thirty reference strains of staphylococci, 76 strains isolated from confirmed
      cases of subclinical mastitis and 10 strains from the teat tip skin and the mouth
      of sucking lambs were assigned to species using four biochemical methods. These
      were the commercially available micromethods API Staph and Staph-Zym; the
      specialized laboratory method Rosco Set and Reactions in Standard Laboratory
      Culture Media (SLCM). The Rosco Set assigned species to all the strains, the SLCM
      to 96.5%, the Staph-zym to 86.1% and the API Staph to 81.4%. API Staph and the
      SLCM favoured the 'aureus' group with the 'epidermidis' second, while the reverse
      was true for the other two methods. All the identification methods assigned the
      same species to only 29% of the tested isolates, causing considerable variation
      in the number of species identified within each group. This variation indicates
      that reported species prevalence from cases of ovine mastitis should be viewed
      with caution.

PMID- 9564273
TI  - Effect of a set stabled environmental control on pulmonary function and airway
      reactivity of COPD affected horses.
AB  - The aim of this study was to evaluate the respiratory function of horses affected
      with chronic obstructive pulmonary disease (COPD) when maintained in a barn on
      wood shavings and fed grass silage for a period of 6 weeks. The mechanics of
      breathing, blood gas analysis and bronchial reactivity were examined on five
      horses with COPD at the end of the environment-controlled period (Period B) and
      the results compared with values obtained after 2 months at pasture (Period A)
      and after the onset of clinical signs of acute crisis (Period C). The results
      showed that clinical and functional parameters were similar in healthy horses and
      in COPD horses placed on pasture or stabled and fed grass silage. Moreover, the
      bronchial reactivity of COPD horses at pasture was similar to the bronchial
      reactivity of healthy horses. COPD horses fed grass silage however presented a
      bronchial reactivity intermediate between those measured after Period A and
      Period C which suggested they would be more susceptible to develop
      bronchoconstriction when in contact with inhaled irritants.

PMID- 9564274
TI  - Evaluation of recombinant bovine somatotropin in the treatment of ovine pregnancy
      toxaemia.
AB  - Forty multigravid ewes with naturally-occurring ovine pregnancy toxaemia were
      treated with a concentrated oral dextrose and electrolyte solution administered
      three times daily an oral and a single subcutaneous injection of either a slow
      release formulation of 160mg recombinant bovine somatotropin (n = 17) or placebo
      injection (n = 23). A higher recovery rate was achieved in ewes treated with
      160mg recombinant bovine somatotropin compared with controls (58.8 versus 34.8%,
      respectively), and more lambs were born alive and survived to 24th from treated
      ewes (15 of 46 lambs; 32.6%) compared with control ewes (12 of 62 lambs; 19.4%)
      but the treatment effects were not significantly different from the control group
      (P > 0.05).

PMID- 9564275
TI  - Effect of ketoprofen on PAF-induced bovine platelet aggregation.

PMID- 9564276
TI  - Partitioning psychological and physical sources of transport-related stress in
      young cattle.

PMID- 9564277
TI  - Post mortem pH decline as influenced by species in different Rhea muscles.

PMID- 9564278
TI  - Distribution of collagen in the vaginal wall of ewes.

PMID- 9564279
TI  - Plan and operation of the NHANES I Epidemiologic Followup Study, 1992.
AB  - OBJECTIVES: The NHANES I Epidemiologic Followup Study (NHEFS) is a longitudinal
      study that uses as its baseline those adult persons 25-74 years of age who were
      examined in the first National Health and Nutrition Examination Survey (NHANES
      I). NHEFS was designed to investigate the association between factors measured at
      baseline and the development of specific health conditions. The three major
      objectives of NHEFS are to study morbidity and mortality associated with
      suspected risk factors, changes over time in participants' characteristics, and
      the natural history of chronic disease and functional impairments. METHODS:
      Tracing and data collection in the 1992 Followup were undertaken for the 11,195
      subjects who were not known to be deceased in the previous surveys. No additional
      information was collected in the 1992 NHEFS for the 3,212 subjects who were known
      to be deceased before the 1992 NHEFS data collection period. RESULTS: By the end
      of the 1992 NHEFS survey period, 90.0 percent of the 11,195 subjects in the 1992
      Followup cohort had been successfully traced. Interviews were conducted for 9,281
      subjects. An interview was conducted for 8,151 of the 8,687 surviving subjects;
      551 interviews were administered to a proxy respondent because the subject was
      incapacitated. A proxy interview was conducted for 1,130 of the 1,392 decedents
      identified in the 1992 NHEFS. In addition, 10,535 facility stay records were
      collected for 4,162 subjects reporting overnight facility stays. Death
      certificates were obtained for 1,374 of the 1,392 subjects who were identified as
      deceased since last contact. Approximately 32 percent of the NHEFS cohort is
      known to be deceased with a death certificate available for 98 percent of the
      4,604 NHEFS decedents.

PMID- 9564280
TI  - Ambulatory care visits to physician offices, hospital outpatient departments, and
      emergency departments: United States, 1996.
AB  - OBJECTIVE: This report describes ambulatory care visits in the United States
      across three ambulatory care settings--physician offices, hospital outpatient
      departments, and hospital emergency departments. Statistics are presented on
      selected patient and visit characteristics for all ambulatory care visits and
      separately for each setting. METHODS: The data presented in this report were
      collected by means of the 1996 National Ambulatory Medical Care Survey (NAMCS)
      and the 1996 National Hospital Ambulatory Medical Care Survey (NHAMCS). These
      surveys are part of the ambulatory care component of the National Health Care
      Survey that measures health care utilization across a variety of providers. The
      NAMCS and NHAMCS are national probability sample surveys of visits to office
      based physicians (NAMCS) and visits to the outpatient departments and emergency
      departments of non-Federal, short-stay and general hospitals (NHAMCS) in the
      United States. Sample data are weighted to produce annual estimates. RESULTS:
      During 1996 an estimated 892 million visits were made to physician offices,
      hospital outpatient departments, and hospital emergency departments in the United
      States, an overall rate of 3.4 visits per person. Visits to office-based
      physicians accounted for 82.3 percent of ambulatory care utilization, followed by
      visits to emergency departments (10.1 percent) and outpatient departments (7.5
      percent). Persons 75 years and over had the highest rate of ambulatory care
      visits. Females had significantly higher rates of visits to physician offices and
      hospital outpatient departments than males did. About two-thirds of ambulatory
      care visits by black persons were to physician offices. There were an estimated
      129.3 million injury-related ambulatory care visits during 1996 or 48.9 visits
      per 100 persons.

PMID- 9564281
TI  - Sample design, sampling weights, imputation, and variance estimation in the 1995
      National Survey of Family Growth.
AB  - OBJECTIVES: Cycle 5 of the National Survey of Family Growth (NSFG) was conducted
      by the National Center for Health Statistics (NCHS) in 1995. The NSFG collects
      data on pregnancy, childbearing, and women's health from a national sample of
      women 15-44 years of age. This report describes how the sample was designed,
      shows response rates for various subgroups of women, describes how the sampling
      weights were computed to make national estimates possible, shows how missing data
      were imputed for a limited set of key variables, and describes the proper ways to
      estimate sampling errors from the NSFG. The report includes both nontechnical
      summaries for readers who need only general information and more technical detail
      for readers who need an in-depth understanding of these topics. METHODS: The 1995
      NSFG was based on a national probability sample of women 15-44 years of age in
      the United States and was drawn from 14,000 households interviewed in the 1993
      National Health Interview Survey (NHIS). Of the 13,795 women eligible for the
      NSFG, 10,847 (79 percent) gave complete interviews. RESULTS: This report
      recommends using weighted data for analysis and a software package that will
      estimate sampling errors from complex samples (for example, SUDAAN or comparable
      software). The rate of missing data in the 1995 NSFG was very low. However,
      missing data were imputed for 315 key variables, called "recodes." Of the 315
      recodes defined for Cycle 5, 271 variables had missing data on less than 1
      percent of the cases; only 44 had 1 percent or more with missing data. These
      missing values were imputed for all of these 315 variables. The imputation
      procedures are described in this report.

PMID- 9564282
TI  - Prophylactic inspiratory muscle training in patients undergoing coronary artery
      bypass graft.
AB  - Pulmonary complications after cardiac surgery are a leading cause of
      postoperative morbidity and mortality. Respiratory muscle weakness may contribute
      to the postoperative pulmonary abnormalities. We hypothesized that: (1) there is
      a decrease in inspiratory muscle strength (PImax at residual volume) and
      endurance (Pmpeak/PImax) following coronary artery bypass graft (CABG); (2) this
      weakness is associated with reduced pulmonary function tests (PFTs), impaired gas
      exchange, and a higher rate of pulmonary complications; and (3) prophylactic
      inspiratory muscle training (IMT) can prevent those changes. Eighty-four
      candidates for CABG, with ages ranging from 33 to 82 years, were evaluated prior
      to operation and randomized into two groups: 42 patients underwent IMT using a
      threshold trainer for 30 min/day for 2 weeks, 1 month before operation (group A);
      42 patients served as a control group and underwent sham training (group B).
      There was a significant decrease in respiratory muscle function, PFTs, and gas
      exchange in the control group following CABG, whereas these parameters remained
      similar to those before entering the study in the training group. The differences
      between the groups were statistically significant. In addition 11 (26%) patients
      in the control group but only 2 (5%) in the training group needed postsurgical
      mechanical ventilation longer than 24 hours, CABGs have a significant
      deteriorating effect on inspiratory muscle function, PFTs, and arterial blood
      gases. The decrease in these parameters can be prevented by prophylactic
      inspiratory muscle training, which may also prevent postsurgical pulmonary
      complications.

PMID- 9564283
TI  - Excision curettage and allografting of giant cell tumor.
AB  - Between 1987 and 1994 we followed 22 patients with giant cell tumors involving
      the long bones. Their average age was 31 years (range 17-50 years). Five patients
      had grade II tumors and the other 17 grade III lesions. The average volume of
      lesions after curettage was 231 ml (range 56-450 ml). All of the patients
      underwent a modified excisional curettage, and the cavity was filled with deep
      frozen allogenic corticocancellous bone graft with supplementary fixation. Two
      patients developed postoperative complications including a superficial wound
      infection in one case and a traumatic tibial plateau fracture in one case. The
      overall outcome was good or excellent in 91% of the patients (i.e., 20/22 cases).
      There was no degenerative joint arthritis and, surprisingly, no instance of tumor
      recurrence. Allograft infection and fracture were not present. An allogeneic
      cortical strut with cancellous bone graft can be used safely and is effective for
      grafting cavitary lesions created after complete removal of the tumor.

PMID- 9564284
TI  - Penetrating chest injuries: unusually high incidence of high-velocity gunshot
      wounds in civilian practice.
AB  - Penetrating chest injuries are a challenge to the thoracic or trauma surgeon.
      Penetrating thoracic trauma, especially that due to high-velocity gunshot wounds,
      is increasing at an alarming rate in our region. We report our experience with
      penetrating chest injuries mainly due to high-velocity gunshot wounds. During a
      period of 6 years we retrospectively reviewed the hospital records of 755
      patients admitted to the Department of Thoracic and Cardiovascular Surgery, Dicle
      University School of Medicine, with the diagnosis of penetrating thoracic trauma.
      The mean age was 27.48 years, and 89-8% were male. The causes of penetrating
      injury were stab wounds in 45.3% and gunshot wounds in 54.7%. About 30% of the
      wounds were due to high-velocity gunshots; and among the gunshot wounds 56.2%
      were due to high-velocity shots. The most common thoracic injury was hemothorax
      (n = 190) followed by hemopneumothorax (n = 184). Isolated thoracic injuries were
      found in 53% of the patients. Nonoperative management was sufficient in 92% of
      the patients. Thoracotomy was performed in 8.1%. The mean duration of
      hospitalization was 11.2 days. The mean injury severity score (ISS) was 20.17 +/-
      13.87. The morbidity was 23.3% and the mortality 5.6%. Fifty percent of all
      deaths were due to adult respiratory distress syndrome. Altogether 17% of
      patients with an ISS > 25 died, whereas only 0.9% of those with a score < 16
      died. The mortality due to firearms was 8.95%. We concluded that in civilian
      practice chest tube thoracostomy remains by far the most common method of
      treating penetrating injury to the chest. The easy availability of high-velocity
      guns will continue to increase the number of civilians injured by these weapons.

PMID- 9564285
TI  - Cytokine patterns in patients who undergo hemofiltration for treatment of
      multiple organ failure.
AB  - The excessive uncontrolled activation of inflammatory cells and mediators after
      trauma or major surgery plays a key role in the development of adult respiratory
      distress syndrome and multiple organ system failure (MOSF). In the past elevated
      cytokine levels were shown to influence the outcome of these patients adversely.
      There are diverging results regarding the removal of circulating cytokines by
      various methods of hemopurification for clinical improvement of MOSF. Seven
      patients after trauma or major surgery underwent continuous venovenous
      hemofiltration (CVVH) for the treatment of severe organ failure of the heart and
      lungs (Murray score 2.74) but not for renal or liver failure. The cytokine levels
      were measured at the beginning and 15, 60, 120, and 240 minutes after initiation
      of CVVH (measure points MP1-5). Clinical improvement during the treatment was
      monitored, and correlation with cytokine levels was evaluated. Arterially
      measured tumor necrosis factor alpha rose from 11.14 ng/ml to 17.86 ng/m1 (p <
      0.05). Arterial interleukin-6 (IL-6) levels significantly decreased during CVVH
      from 1284.7 ng/m1 to 557.9 ng/m1; IL-8 levels simultaneously decreased from an
      initial peak of up to 154.4 ng/m1 at MP3 to 97.3 ng/m1 at MP5. The drop in serum
      IL-6 and IL-8 levels closely correlated with clinical improvement. After 2 hours
      of CVVH the hemodynamic situation improved significantly, as revealed by a
      decrease in catecholamine expenditure, an increase in arterial pressure, and a
      decrease in pulmonary artery pressure. Moreover, 2 hours after the initiation of
      CVVH the oxygenation index rose significantly and correlated well with the drop
      in shunt fraction. The Murray score significantly fell to 1.86. The removal of IL
      6 and IL-8 by CVVH after initial stimulation correlates with clinical
      improvement, which was demonstrated by significantly improved oxygenation and
      hemodynamics from 2 hours after the initiation of CVVH onward. The elimination of
      cytokines and several mediators by CVVH may contribute to the cardiopulmonary
      improvement of critically ill patients. In comparison with the clinical control
      group (n = 7), which was comparable in terms of MOSF, no intervention led to a
      similar improvement in cardiorespiratory failure, and overall two of these
      patients died. Moreover, patients of the control group experienced a significant
      longer stay at in the intensive care unit.

PMID- 9564286
TI  - Abdominal sonography screening of clinically diagnosed or suspected appendicitis
      before surgery.
AB  - We conducted a prospective study to evaluate the value of abdominal sonography in
      the diagnosis of acute appendicitis and determine the need for abdominal
      sonography before operation. Altogether 191 patients with clinically diagnosed or
      suspected appendicitis underwent an abdominal sonography examination performed by
      a staff surgeon before operation. The sonographic findings are classified into
      three categories: appendicitis, other diseases, or normal screening. A total of
      158 patients (82.7%) with positive findings of appendicitis proceeded to surgery;
      18 patients (9.4%) were found to have other diseases, and they were treated for
      their conditions; and 15 patients (7.9%) with normal screening were discharged
      from the hospital and were reevaluated 2 weeks later. Only one patient had a
      false-negative finding. Of the 158 patients undergoing operation, 143 (90.5%)
      were proved to have appendicitis by the pathologic reports. A total of 32
      negative appendectomies (16.8%) were prevented after sonographic examination.
      Abdominal sonography for detecting acute appendicitis had a sensitivity of 99.3%,
      a specificity of 68.1%, an accuracy of 91.6%, a positive predictive value of
      90.5%, and a negative predictive value of 97.0%. The value of meticulous history
      taking, physical examination, and laboratory tests cannot be overemphasized. Our
      experience suggests that patients with clinically diagnosed or suspected acute
      appendicitis should routinely undergo abdominal sonography examination, performed
      by an experienced surgeon, to further decrease the negative appendectomy rates.

PMID- 9564287
TI  - Transcylindrical cholecystectomy: new technique for minimally invasive
      cholecystectomy.
AB  - Minilaparotomy cholecystectomy presents exposition difficulties, and laparoscopy
      requires expensive equipment and additional training. Laparotomy is more painful,
      causes trauma to the abdominal wall, and requires a longer convalescence; it is
      also less aesthetic. We present a new technique for minilaparotomy
      cholecystectomy, transcylindrical cholecystectomy (TC), based on the introduction
      of a 3.8- or 5.0-cm diameter cylinder (10.0 cm long). The cylinder serves the
      purpose of separating and isolating the hepatocystic triangle from the
      surrounding structures, thereby providing a stable surgical field and adequate
      vision of the hepatocystic triangle so the technique can be performed safely.
      Patients who have been diagnosed with symptomatic cholelithiasis, who are
      convalescent from biliary pancreatitis, or who have acute cholecystitis have been
      treated consecutively by TC. We have carried out the procedure on 116 occasions,
      94 using the 3.8-cm cylinder and 28 with the 5.0-cm cylinder; both cylinders were
      used in 6 cases. The indications for using the 5.0-cm cylinder were mainly
      cholecystitis, pancreatitis, choledocholithiasis, and difficulty with the 3.8-cm
      cylinder. The result is a 4.5- or 7.0-cm incision. We had difficulty recognizing
      the anatomy in 11 dissections so we had to enlarge the incision. We have not had
      accidents related to placement of the cylinder, hemorrhage, or bile duct
      injuries. The median operating time was 43 minutes, and the mean postoperative
      stay was 1.8 days. Postoperative FVC and FEV, reductions were 21.7% and 27.4%,
      respectively. The technique has proved fast, safe, and practicable using
      conventional material. The cost of TC is $701 (US).

PMID- 9564288
TI  - Is percutaneous cholecystostomy the optimal treatment for acute cholecystitis in
      the very elderly?
AB  - In elderly patients emergent cholecystectomy for acute cholecystitis is a high
      risk procedure. We prospectively assessed the value of percutaneous
      cholecystostomy for acute cholecystitis in 38 consecutive elderly (> or = 80
      years) patients. All 38 underwent percutaneous transhepatic cholecystostomy under
      ultrasonographic and fluoroscopic guidance for acute cholecystitis (25 calculous,
      13 acalculous). Eight (21%) patients had acute severe medical problems, such as
      shock and respiratory distress. Thirty-one (82%) patients had chronic severe
      underlying diseases, including cardiovascular and neurologic diseases.
      Cholecystostomy was successful in all 38 patients. Prompt clinical improvement
      was obtained in 36 (95%) patients. Morbidity and mortality rates were 3% and 3%,
      respectively. After cholecystostomy, 10 patients with cholelithiasis underwent
      elective cholecystectomy without serious complications. Two patients underwent
      percutaneous cholecystolithotomy, which produced complete resolution of symptoms.
      Four of 12 patients with and none of 12 without cholelithiasis had recurrent
      cholecystitis after catheter removal during a mean follow-up of 1.8 years. A
      second cholecystostomy was successful in these four patients. Elderly patients
      are often poor surgical candidates because of severe cholecystitis or concomitant
      medical problems. Percutaneous cholecystostomy is a safe, effective treatment for
      acute cholecystitis even in elderly patients. For calculous cholecystitis,
      cholecystostomy can be followed by elective surgery, if possible, or by
      nonsurgical treatment or expectant conservative management in high-risk patients.
      Cholecystostomy may be a definitive treatment for acalculous cholecystitis.

PMID- 9564289
TI  - Induction of heat shock response: effect on the rat liver with carbon
      tetrachloride-induced fibrosis from ischemia-reperfusion injury.
AB  - The role of heat shock pretreatment in the induction of tolerance for ischemia
      reperfusion injury was investigated in rat livers with fibrosis produced by
      carbon tetrachloride (CCI4) injected subcutaneously. The control group (group C,
      n = 56) received no pretreatment except anesthesia, and the heat shock group
      (group HS, n = 56) were exposed to heat shock (42 degrees C) for 15 minutes.
      After a 48-hour recovery all rats were subjected to 30 minutes of warm ischemia.
      Western blotting analysis was employed for heat shock protein (HSP) 72 detection.
      The adenine nucleotide levels in liver tissue and the liver enzyme levels in
      serum were measured before and after ischemic intervention (seven animals were
      used at each of six time point measurements in both groups). HSP72 was induced in
      group HS at greater intensity than in group C. The survival rate on postoperative
      day 7 in group C (3/14) was significantly poorer than that in group HS (14/14) (p
      < 0.01). The higher survival rate in group HS was accompanied by more rapid
      recovery of the adenosine triphosphate level and lower serum levels of liver
      enzymes after reperfusion (p < 0.01 vs. group C). Heat shock preconditioning
      induces HSP72 in the rat liver with fibrosis and provides significantly increased
      tolerance of warm-ischemia reperfusion injury.

PMID- 9564290
TI  - Effective of pneumoperitoneum induced by carbon dioxide and air on tumor load in
      a rat model.
AB  - Laparoscopic surgery for malignant disease is highly controversial mainly due to
      the large number of abdominal wall metastases being reported. Previous
      experimental studies have particularly studied CO2 pneumoperitoneum and its
      effect on tumor development. The purpose of this study was to compare CO2- and
      air-induced pneumoperitoneum with regard to intraperitoneal tumor growth.
      Altogether 39 rats were injected intraperitoneally with 10(5) colonic tumor cells
      and randomly allocated into three groups: 13 rats had a pneumoperitoneum created
      with CO2, 13 with air, and 13 served as controls. Tumor development was
      determined semiquantitatively by a peritoneal cancer index scale after 12 days.
      CO2 and air pneumoperitoneum equally increased intraperitoneal tumor growth
      compared to controls. Pneumoperitoneum induced by CO2 and air seems to increase
      tumor load, but the mechanisms are not established. This finding supports the
      hypothesis that insufflation not only by causing tumor cell movements but in fact
      pneumoperitoneum per se and the used gas are involved in the development of
      abdominal wall metastases after laparoscopic surgery.

PMID- 9564291
TI  - Prevalence of thyroid cancer in hyperthyroid patients treated by surgery.
AB  - A retrospective study has been carried out to evaluate the prevalence of
      malignant thyroid tumors in 202 patients submitted to surgery for
      hyperthyroidism. Thyroid cancer was diagnosed in 12 cases (5.9%); the final
      histologic examination revealed nine papillary carcinomas, one follicular
      carcinoma, and two Hurthle cell carcinomas. Concurrence of hyperthyroidism and
      thyroid cancer was more frequent in patients with single toxic adenomas than in
      those with toxic diffuse or multinodular goiters. In five cases thyroid
      malignancy was detected in the context of the hyperthyroid lesion (three toxic
      adenomas and two diffuse goiters). In eight patients the malignant lesion showed
      a maximum diameter of less than 1 cm, although in five of these cases unfavorable
      histologic features, such as minimal capsular invasion or multifocality, were
      present. All patients presenting with thyroid cancer are currently alive and
      apparently free of residual disease. It is concluded that hyperthyroid patients,
      particularly those with single toxic adenomas, should be carefully evaluated to
      exclude the presence of an associated malignancy and to plan the most appropriate
      therapeutic options.

PMID- 9564292
TI  - Long-term results of polyglactin mesh for the prevention of incisional hernias in
      obese patients.
AB  - The aim of this study was to compare prospectively the incidence of incisional
      hernia in two groups of patients operated on for morbid obesity, with or without
      intraperitoneal polyglactin mesh. From October 1990 to September 1993, a total of
      288 patients were randomly assigned to the two groups. There were 144 patients in
      the mesh group and 144 in the no-mesh group. Altogether 240 patients (83%) were
      reviewed personally, 45 (16%) were interviewed by phone (n = 39) or mail (n = 6),
      and 3 (1%) were inaccessible for follow-up since discharge from the hospital. The
      mean follow-up period was 29.8 months (range 0-67 months). A total of 33
      incisional hernias were observed in the mesh group and 41 in the no-mesh group.
      There was no significant difference in the distribution of herniation time
      between the two groups (p = 0.43). The two main predictive factors of herniation
      were age and weight. In conclusion, the use of an intraperitoneal polyglactin
      mesh does not prevent postoperative incisional hernias in obese patients.

PMID- 9564293
TI  - Overexpression of nm23 protein assessed by color video image analysis in
      metastatic colorectal cancer: correlation with reduced patient survival.
AB  - The function and prognostic significance of the nm23 gene is controversial in
      colorectal cancer (CRC). The aim of this study was to determine if nm23 protein
      expression correlated with the subsequent development of liver metastasis.
      Paraffin-embedded sections of 30 metastasizing CRC primaries and their
      subsequently resected liver secondaries were compared with those of 28
      nonmetastasizing CRCs, 20 adenomas, and 20 cases of normal colonic mucosa.
      Expression of nm23 protein, assayed by immunohistochemistry, was measured using a
      standard semiquantitative scaling system and compared with a microcomputerbased
      color video image analysis (VIA). There was good correlation between color VIA
      and semiquantitative evaluation of nm23 immunoreactivity, confirming the validity
      of quantitative analysis (Pearson's r = 0.88; p < 0.001). Metastasizing CRC
      primaries and secondaries overexpressed nm23 protein when compared with the other
      clinical groups, particularly nonmetastasizing CRC (Student's t-test, p < 0.001).
      Furthermore, more nm23 immunoreactivity was associated with a higher risk of
      death from CRC (log-rank test, p = 0.002). These results suggest that
      overexpression of nm23 is highly associated with liver metastases from CRC and
      reduced survival.

PMID- 9564294
TI  - Radiation enterocolitis: overview of the past 15 years.
AB  - From April 1980 to April 1995 a total of 54 patients (53 women, 1 man) were
      hospitalized in our department for the surgical treatment of radiation
      enterocolitis. Two surgical protocols were applied for these patients: intestinal
      decompression procedures alone (intestinal bypass, colostomy, or both; n = 18) or
      an intestinal resection in addition to decompression (n = 36). The clinical
      factors contributing to survival after irradiation were retrospectively reviewed
      by a multiple variate proportional hazards model. As a result, patients treated
      with decompression procedures alone had an 11 times higher risk for death than
      those treated with the addition of intestinal resection. In the former group, 5
      of 18 patients died of bleeding from the remaining intestine after operation. We
      concluded that surgical resection of the diseased intestine is a useful procedure
      for treating radiation enterocolitis to reduce intestinal bleeding from the
      irradiated intestine.

PMID- 9564295
TI  - Fibrin glue sandwich prevents pancreatic fistula following distal pancreatectomy.
AB  - Pancreatic fistula is a major form of morbidity following pancreatic resection.
      We conducted a nonrandomized clinical trial comparing the sealing and sandwich
      techniques of spraying fibrin glue to prevent pancreatic fistula following distal
      pancreatectomy. The pancreas was transected with a scalpel to identify and suture
      the main pancreatic duct and its small branches. In the sealing group, fibrin
      glue was sprayed over the closed pancreatic stump and sutures. Alternatively, in
      the sandwich group fibrin glue was sprayed so as to cover and join the cut
      surface of the pancreatic remnant, which was then held closed with sutures.
      Altogether 111 patients were included in the study (90 with gastric cancer, 10
      with esophageal cancer, and 11 with pancreatic cancer). Patients were nonrandomly
      assigned to the sandwich or the sealing group. Morbidity was 21.8% for the
      patients in the sandwich group versus 33.9% in the sealing group. Pancreatic
      fistulas occurred in 9.0% of the sandwich group versus 26.8% of the sealing
      group. The incidence of fistula was thus significantly lower in the sandwich
      group. The incidence of fistula was also significantly lower in the sandwich
      group for gastric malignancy patients undergoing extended radical lymphadenectomy
      down to the paraaortic lymph nodes combined with left adrenalectomy. Of the
      patients with gastric malignancy, pancreatic fistulas occurred in 9.3% of the
      sandwich group versus 25.5% of the sealing group. The fibrin glue sandwich
      technique is simple and reliable and should be valuable for complementing other
      prophylactic methods of preventing pancreatic fistula.

PMID- 9564296
TI  - Historical development of surgical instruments exemplified by hemostatic forceps.
AB  - We describe the historical development of surgical instruments exemplified by
      hemostatic forceps, starting with antique and medieval forceps used for the
      arrest of bleeding to modern atraumatic hemostatic forceps used for vascular
      reconstruction. Their development proceeded mainly in three steps: (1)
      development of ligature forceps directly for hemostasis (Celsus, first century
      AD; Pare, 1582; L. Heister, 1743; (2) development of atraumatic forceps, which
      facilitate vascular reconstruction or anastomosis creation by temporarily
      clamping vessels (Hopfner, 1903; Stich, 1907; Jeger, 1913; (3) construction of
      tangential forceps, which, by partially clamping vessels with partial maintenance
      of blood flow, allow the reconstruction or anastomosis of large vessels in a side
      to-side technique. The first tangential occlusion clamp was developed by
      Friedrich Trendelenburg (1844-1924) in 1908, when he established the operative
      treatment for embolism of the pulmonary artery. This clamp was later modified by
      A. W. Meyer (1927) and V.P. Satinsky (ca. 1950).

PMID- 9564297
TI  - Inadvertent intubation of the esophagus with administration of oxygen through a
      nasal catheter.

PMID- 9564298
TI  - Penetrating injuries of the neck.

PMID- 9564299
TI  - Where dentistry stands in light of health care reform.
AB  - The hot topic from Capitol Hill in Washington to Capitol Hill in Jefferson City
      is health care reform. President Clinton started the ball rolling during the
      campaign in 1992 by including health care reform in his platform. He continued
      the effort after his election by appointing his wife, Hillary, to chair a task
      force to present an outline for federal legislation. Since the package was
      presented to Congress, there has been much discussion, lobbying, and rumoring
      about the implications of health care reform and what it could mean to all of us
      as dentists. On the home front, Governor Carnahan has introduced legislation in
      Missouri to reform the health care system. This effort is known as the Missouri
      Health Assurance Plan (H.B. 1622). Missouri Dental Association members are
      vitally concerned about the impact of health care reform on their practice, their
      taxes, their relationship with their patients and employees, and on their ability
      to seek out health care services since each member is also a consumer of health
      care. This article represents answers to some of the questions being asked by MDA
      members in order that they might be more aware of the activities by the MDA, the
      ADA, and other levels of organized dentistry relating to health care reform.

PMID- 9564300
TI  - Guidelines for preventing occupational exposure to TB.

PMID- 9564301
TI  - Stark II: New restrictions on referrals.

PMID- 9564302
TI  - Documenting employee performance and disciplinary problems: Part I.

PMID- 9564303
TI  - Documenting employee performance and disciplinary problems: Part 2.

PMID- 9564304
TI  - Sexual harassment in the dental work place ... a student's experience.

PMID- 9564305
TI  - Ergo space positioning. Heightening office efficiency.

PMID- 9564306
TI  - Captive rage.
AB  - Providing dental care for the sexual abuse survivor requires a mixture of
      technical and interpersonal skills. It is often necessary to counteract the
      effects of long term dental neglect complicated by the psychological aspects of
      the oral cavity. Feelings of loss of control of an important psychologically and
      sexually charged area must be dealt with effectively. Dentists must be flexible
      in their approach to the patient, yet never compromise the standard of care.
      Examination of case histories provides illustrations and examples.

PMID- 9564307
TI  - The limited liability company. A new alternative.

PMID- 9564308
TI  - Circumferential and bilateral subperiosteal implant technique for the atrophic
      mandible.

PMID- 9564309
TI  - Managed care contracts.

PMID- 9564310
TI  - Communications checksheet will ease relations with laboratories.

PMID- 9564311
TI  - Preparation leads to successful practice sales.

PMID- 9564312
TI  - Interviewing to find the right associate or buyer for your practice.

PMID- 9564313
TI  - A new information base: integrated and networked computers.

PMID- 9564314
TI  - Treatment room computers: enhanced scheduling, examination and recordkeeping.

PMID- 9564315
TI  - The legalities of patient confidentiality.

PMID- 9564316
TI  - DR: a practical approach that works. Direct reimbursement.

PMID- 9564317
TI  - Malpractice review.

PMID- 9564318
TI  - The impact of HIV and AIDS on dentistry in the next decade.

PMID- 9564319
TI  - Staying out of court.

PMID- 9564320
TI  - Dentistry preventing family violence.
AB  - Dentistry has a long history of dealing with one form of family violence, child
      maltreatment. However, a recent national survey shows that dentists are not
      living up to their legal and ethical obligations to report suspected child
      victims. Dentistry needs to be equally concerned with adult victims of family
      violence--the victims of spousal abuse and elder abuse and neglect. Successful
      child abuse prevention programs need to expand to cover all of family violence.
      All health care professionals need education and awareness training to help
      develop the necessary attitudes to deal with all victims of family violence.

PMID- 9564321
TI  - Treatment of HIV-positive patients.

PMID- 9564322
TI  - Conflicts in esthetic dentistry.

PMID- 9564323
TI  - AIDS update and jury service.

PMID- 9564324
TI  - The computer bandwagon--has everyone else jumped on?
AB  - A survey of 1,179 dentists in Kansas and Missouri was mailed in an effort to
      determine their current use of computers. There was a completed return of 458
      surveys (39 percent). Of those responding, 64.4 percent indicated they had a
      computer in their home or office. Of those with computers, 73 percent were IBM or
      IBM compatible, 11.5 percent were Macintosh and 15.5 percent were other.
      Comparison of this survey with a similar survey completed in Indiana indicates
      that computer usage by dentists appears to be increasing but not at the same rate
      as the advances in computer technology.

PMID- 9564325
TI  - Child abuse and dentistry--what you should know.
AB  - Dentistry must become more aware of its moral, legal and ethical responsibilities
      in recognizing and reporting child abuse and neglect. All dental professionals
      must be aware of the seriousness of the problems of child maltreatment, and
      understand that children do not just get hurt in abuse and neglect, they often
      die as a direct result of their maltreatment. It has been said that victims of
      child abuse and neglect fall into only two categories--those who lived through it
      and those who did not.

PMID- 9564326
TI  - Dentistry in cyberspace.

PMID- 9564327
TI  - Office web site. Patients can access the Internet during their dentist visits.

PMID- 9564328
TI  - Sneak a peek into cyberspace.

PMID- 9564329
TI  - Computers invade the dental practice.

PMID- 9564330
TI  - Anterior crowns & porcelain laminate veneers: a conservative approach.
AB  - The final results of this case were pleasing to the patient and the dentist
      (Fig.5). The diastemas had been closed (Fig. 6), and the bioesthetic symmetry and
      harmony had been restored (Fig. 7). The patient reported an increase in self
      confidence with his peers and professors, especially during assignments both at
      work and at the university. (Fig. 8) I want to especially thank Felipe Don
      Sanders, C.D.T. for his skill in producing the excellent laboratory work for this
      case.

PMID- 9564331
TI  - Legislative change--not a hot topic of conversation.

PMID- 9564332
TI  - Undisturbed sleep. A research-based change to improve safety on a secure long
      term unit.

PMID- 9564333
TI  - CNA study predicts severe nursing shortage.

PMID- 9564337
TI  - Australian workplace agreements.

PMID- 9564334
TI  - Northern nursing: a type of advanced nursing practice.

PMID- 9564339
TI  - Nurses, nursing and the unlicensed worker providing nursing care.
AB  - The issue of the unlicensed worker performing nursing work is indeed contentious.
      However, this worker, known variously as the Assistant in Nursing (AIN), the
      Personal Care Attendant (PCA), the Direct Care Worker, the Community Worker and
      so on has been part of the health care scene for many years.

PMID- 9564338
TI  - Credentialing specialty nursing practice: a dissenting view.
AB  - Orderly development of specialty practice has been a professional issue in
      Australian nursing since the 1991 visit of Dr Margretta Madden Styles of the
      International Council of Nurses. In response, the ANF established the National
      Nursing Organisations (NNOs)--leaders of about 60 national specialty groups who
      meet twice each year to ensure orderly development of specialty practice. The
      most recent issue raised in this forum was credentialing.

PMID- 9564340
TI  - National nursing organisations--advancing the practice of nursing.

PMID- 9564341
TI  - Nursing the patient receiving continuous positive airway pressure therapy.
AB  - The shortfalls of standard oxygen therapy and the increasing trend toward
      avoiding mechanical ventilation has led to greater use of Continuous Positive
      Airway Pressure (CPAP) therapy. What was once the domain of intensive care units
      has now become a common therapy in many acute clinical settings.

PMID- 9564342
TI  - What specific challenges has health reform brought for nursing leaders and how
      can nurses work together to address these?

PMID- 9564343
TI  - How can the bedside nurse take a leadership role to affect change for the future?

PMID- 9564344
TI  - What roles do unions have in preparing nursing leaders to effective change for
      the future?

PMID- 9564345
TI  - What are the options in education for nurses to address the challenges today and
      into the future?

PMID- 9564346
TI  - What does the public expect from nursing leaders in the reformed health system?

PMID- 9564347
TI  - Northern nurses enjoy challenge and lifestyle. Saskatchewan Health and Northern
      Health Services.

PMID- 9564348
TI  - The psychological and emotional impact of living with an automatic internal
      cardioverter defibrillator (AICD): how can nurses help?
AB  - The introduction of the Automatic Internal Cardioverter Defibrillator (AICD) has
      greatly improved the mortality rates associated with sudden cardiac events (Moss
      et al 1996, McCarthy 1997, Trappe et al 1997). Little is known about the
      consequences of living with this device for patients and their families.
      Biomedical influences have resulted in the devices's success being measured on
      physical adaptation, with data on suitability, reliability, and efficiency of
      AICDs as a therapeutic measure. What seems to be of equal priority now is to
      obtain insights as to the emotional and psychological consequences of such
      treatment, and the effects these may have on outcomes and utilization of health
      care resources. AICD patients have described many powerful emotions arising from
      receiving this device, which are often heightened at discharge, yet little is
      known of the reasons for this (James 1997a). It is essential that individuals'
      and their families' perceptions of their experiences are understood so that
      clinical staff can not only meet the technological and safety needs of this
      group, but also assist them to adjust to living with an AICD. Families of AICD
      patients report significant emotions arising from their support of AICD patients,
      and describe their own needs and problems. Nevertheless, the influence of, and
      the effects on the family are often underestimated within AICD patient care. A
      shift away from a purely individualistic approach towards a more family-centred
      approach is suggested, arguably enabling the role of family members to be
      recognized, supported and developed. Qualitative research in this area is needed
      to inform clinical nursing practice and assist in development of clinical
      expertise to address the important issues for patients and families. This should
      enable them to return to their everyday lives with appropriate support. Education
      of healthcare professionals in a wide variety of clinical areas is needed to
      ensure a sound body of knowledge, as a basis for development of a more holistic
      approach to care which encompasses and recognizes the feelings and emotions
      evoked from receiving this device.

PMID- 9564349
TI  - Recreational drug users in the ICU: a review.
AB  - The purpose of this paper is to examine why patients who use recreational drugs
      which depress the central nervous system might experience such severe
      difficulties that they require an admission to an Intensive Care Unit (ICU). The
      specific problems each substance may cause will be examined, as will the problems
      common to all. In conclusion, there is a brief discussion of some of the social,
      educational and management issues that drug victims present.

PMID- 9564350
TI  - Patient management in head injury care: a nursing perspective.
AB  - Through a review of the literature, this article provides a consideration of
      nursing responsibilities and nursing care in the management of patients with head
      injuries. A brief review of the pathophysiology of head injury is followed by a
      description of intracranial pressure (ICP) monitoring and cerebral perfusion
      pressure (CPP) measurement, using the Camino fibreoptic catheter and monitor,
      with exploration of pulse and trend waveforms and their significance in assessing
      cerebral compliance. Jugular venous bulb saturation (SjO2) monitoring adds
      another dimension to the assessment of neurological damage by demonstrating
      cerebral tissue perfusion and cerebral metabolic rate, and this is also
      discussed. After identification of assessment as a crucial part of the nursing
      role, aspects of nursing care of head-injured patients are discussed. The
      discussion of respiratory support measures includes the controversial use of
      hyperventilation in reducing ICP, the prevention of hypoxia, the risk of
      respiratory complications, the use of suctioning and turning to prevent these and
      the problems associated with these nursing care measures. Other aspects of care
      are also considered, including careful positioning and temperature control, and
      the benefits of mild hypothermia.

PMID- 9564351
TI  - Nursing care of the Paratrend 7 sensor.
AB  - The Paratrend 7 sensor is a continuous intravascular blood gas sensor that
      consists of a miniaturized Clark-type PO2 electrode, fibreoptic pH and PCO2
      optodes and a thermocouple, the monitor continuously displays the measured pH,
      PaO2 PaCO2 and temperature of the blood, and the calculated oxygen saturation, BE
      and SBC. After 7 years of caring for over 200 patients following insertion of the
      sensor, we describe our nursing experience with particular emphasis on the
      adequate fixation of the cannula, sensor system and connectors. The maintenance
      of the sensor through adequate flushing of the arterial line and care of the
      insertion site is described. Also outlined are the potential advantages to
      nursing practice of this new monitoring system, with particular reference to
      early warning of deterioration in respiratory function, closer control of
      mechanical ventilation and reduction in blood gas sampling and the errors
      inherent therein.

PMID- 9564352
TI  - Multiple stab wounds: a short-term respiratory case study.
AB  - Respiratory management is a role that is of paramount importance to intensive
      care nurses. Proactive nursing allows a nurse to have a positive effect on a
      patient's condition by actively improving the patient's status and setting
      priorities of care, avoiding deterioration wherever possible. In this account of
      the respiratory management of a patient who has sustained bilateral
      pneumothoraces following multiple stab wounds to the chest and back, the
      physiological assessment of the patient is described and a proactive respiratory
      plan of care is formed. Anatomy, physiology and pathophysiology in relation to
      pneumothoraces, metabolic acidosis and magnesium links with functional residual
      capacity are addressed. The potential risk of Adult Respiratory Distress Syndrome
      (ARDS) following direct and indirect lung injury is discussed. Recent research
      into ventilation modes and into areas of nursing practice relating to respiratory
      management are also considered.

PMID- 9564353
TI  - Concept analysis of trust: a coronary care perspective.
AB  - Patients admitted to the coronary care unit following either myocardial
      infarction, severe left heart failure or rhythm disturbances frequently have
      difficulty conceptualizing a 'broken heart'. The aim of this paper is to provide
      a greater understanding of the term 'trust' in relation to patient care,
      utilizing the concept analysis framework of Walker & Avant. Trust has been
      identified as an essential element in the nurse-patient relationship; due to its
      abstract nature it would appear that we as critical care nurses have been naive
      and have over-simplified the concept. Indeed, it is suggested that we could learn
      from our patients, in order to contribute to an effective nurse-patient
      relationship.

PMID- 9564354
TI  - Physiological changes occurring with positive pressure ventilation: Part Two.
AB  - Although the physiological effects of positive pressure ventilation are numerous,
      sometimes undesirable and have varying degrees of significance, positive pressure
      ventilation still plays a major role in the resuscitation and treatment of
      critically ill patients. Advances in the various methods of delivering positive
      pressure, especially when incorporating spontaneous breathing, have reduced the
      severity of complications. Despite serious complications, mechanical ventilation
      has advantages. When it is instituted for ventilatory and hypoxaemic respiratory
      failure, the benefits can be viewed in the context of the work of breathing.
      Spontaneous breathing normally requires 5% of total oxygen delivery to meet its
      demands. In lung disease, the ratio of oxygen consumption by the respiratory
      muscles to whole body oxygen consumption can increase to 25-30% (Henning 1986,
      Pinksy 1990). Mechanical ventilation reduces the energy demand of respiratory
      muscles and increases the oxygen delivery to other vital organs. When mechanical
      ventilation improves hypoxaemia and/or hypercarbia, or significantly decreases
      the work of breathing, it may also normalize associated changes in heart rate
      (Perel & Pizov 1991 p53). When cardiac output is increased in response to the
      increased work of breathing and associated stress, the institution of mechanical
      ventilation may beneficially lower the cardiac output simply due to the decrease
      in oxygen demand; thus the physiological reduction in cardiac output may not
      necessarily be regarded as a complication. The effects of raised intrathoracic
      pressure during mechanical ventilation may be beneficial when used to prevent or
      reduce pulmonary oedema, though problematic in some other situations. Mechanical
      ventilation is a life-saving treatment which has many associated complications;
      nurses have to accept the unavoidable hazards and adapt their nursing care to
      minimize their effects.

PMID- 9564355
TI  - Ecstasy poisoning.
AB  - The substance Ecstasy, which has become synonymous with the rave culture, has
      received much attention in recent times as a result of several well-publicized
      deaths among young 'users'. What is Ecstasy and what is the management of its
      toxicity in patients admitted to hospital?

PMID- 9564356
TI  - Practice and employment trends among nurse practitioners in New York State.
AB  - This study describes nurse practitioners' (NPs) practice and employment trends,
      primary care/direct patient care involvement, scope of practice issues,
      productivity, and demographic characteristics. Data were collected by mailed
      survey from 2,499 NPs in New York State. NPs were predominantly certified as
      Adult, Pediatric or Family NPs. The vast majority of NPs were working (64.1% full
      time; 22.7% part-time). Fifty percent said they spend over 80% of their time
      providing primary care. Over 50% of the NPs employed in non-hospital settings
      said that their organizations had contracts with four or more managed care
      organizations.

PMID- 9564357
TI  - The Special Surveillance Breast Program: a model of intervention for women at
      high risk for breast cancer.
AB  - The Special Surveillance Breast Program (SSBP) is a long-term, comprehensive,
      multidisciplinary program for women determined to be at high risk for the
      development of breast cancer. Because the women who attend this program are
      otherwise healthy but concerned about their risk for breast cancer, current and
      relevant information is required to address their concerns regarding the
      possibility of developing breast cancer. The purpose of this article is to
      describe the risk factors that indicate eligibility for the program, the
      structure of the program, and the results of an assessment that identified the
      needs of this special population.

PMID- 9564358
TI  - Nurses' reflections on ethical decision making: implications for leaders.
AB  - This study documents moral/ethical situations that nurses in acute care hospitals
      experience as described by the nurses themselves. Findings show on-going evidence
      of caring, connectedness, and context. Decisions made often showed a balance
      between perceived ideal action and realistic action. This study also demonstrates
      that nurses need more opportunity for ethical reflection, that employers must
      become more involved in ethics education, and that further study of ethical
      decision making is needed as professionals and clients become more diverse.

PMID- 9564360
TI  - What do you do to help patients relieve their anxiety about undergoing such
      procedures as biopsy, cast removal, cardiac catheterization, etc.?

PMID- 9564359
TI  - Bibliography: breast cancer.

PMID- 9564361
TI  - Dietary soy and hot flushes.

PMID- 9564362
TI  - Ruling out DVT.

PMID- 9564363
TI  - Decreasing complications in type 2 diabetes.

PMID- 9564364
TI  - Lessening the pain of lidocaine injection.

PMID- 9564365
TI  - Rescreening of Pap smears.

PMID- 9564366
TI  - Treatment of premature ejaculation.

PMID- 9564367
TI  - Antibiotics for acute maxillary sinusitis in adults.

PMID- 9564368
TI  - Yohimbine for erectile dysfunction.

PMID- 9564369
TI  - Neonatal respiratory distress in the community hospital: when to transport, when
      to keep.
AB  - Neonatal respiratory distress is a common problem confronting family physicians.
      Although respiratory distress may represent a benign, self-limited process, it
      may also be the first sign of sepsis or serious cardiopulmonary disease. Because
      it is crucial to differentiate the two, we offer a practical approach to the
      treatment of neonatal respiratory distress at community hospitals. Our method,
      the Rule of 2 Hours, is based on readily accessible clinical findings. We believe
      it will help physicians detect babies at risk for serious problems, but will not
      result in unnecessary referral of neonates that are simply adapting to
      extrauterine life.

PMID- 9564370
TI  - Primary care and the community.

PMID- 9564371
TI  - The four community dimensions of primary care practice.
AB  - BACKGROUND: Despite the growing belief that "the community" should play a larger
      role in the work of physicians, there is no clear understanding of exactly how
      physicians should participate in their communities. The primary goals of this
      study were to propose and test an organizing framework that identified four
      distinct categories of activities whereby physicians can interact with their
      communities: (1) identifying and intervening in the community's health problems;
      (2) responding to the particular health issues of local cultural groups when
      caring for patients; (3) coordinating local community health resources in the
      care of patients; and (4) assimilating into the community and its organizations.
      Other goals were to characterize physicians' level of involvement in each of
      these four types of community activities, and to identify the correlates of
      greater and lesser involvement. METHODS: A questionnaire was mailed to a random
      sample of 500 young primary care physicians in the United States. The response
      rate was 66.6%. Physicians reported how confident they were in performing each of
      15 specific community-relevant activities. Confidence ratings were factor
      analyzed to test the hypothesis that physician involvement in community
      activities can be organized into the four proposed categories. Physicians also
      self-rated their involvement in various community activities within each of these
      four categories, and predictors of involvement were identified through ordinary
      least-squares regression models. RESULTS: Using factor analysis, the community
      activities sorted cleanly into the four postulated community dimensions of
      medical practice, providing a measure of validation for the distinctiveness of
      the four dimensions. Physicians reported active involvement in some activities
      (eg, speaking to community groups and gaining acceptance in their communities)
      and little involvement in other activities (eg, working with community groups to
      address local health problems, familiarity with local women's shelters). Contrary
      to expectations, physicians who worked with minority and poorer patient
      populations and counties generally reported less community involvement.
      Physicians caring for more patients covered by HMO or capitated health insurance
      plans also reported lower participation in their communities. CONCLUSIONS: This
      study provides support for the hypothesis that the community plays a role in the
      work of physicians that can be categorized into four types of activities. This
      framework may help physicians and practices recognize the breadth of ways they
      can meet the growing demand that they approach their work with a community
      perspective.

PMID- 9564372
TI  - Tubes, antibiotic prophylaxis, or watchful waiting: a decision analysis for
      managing recurrent acute otitis media.
AB  - BACKGROUND: The two most frequently used options to reduce the occurrence of
      acute otitis media (AOM) are tympanostomy tubes and prophylactic antibiotics. The
      goal of this study was to create a decision model to identify which intervention,
      if any, is preferred from the perspective of parents with young children.
      METHODS: We developed a decision analysis model based on probabilities obtained
      from the literature and outcome disutilities obtained by interviewing parents.
      These parameters were placed into the model along with the anticipated number of
      episodes of AOM a child was expected to have in the coming year without
      intervention. Sensitivity analyses were performed on the effectiveness of the
      interventions, the disutilities (burdens associated with specific outcomes or
      interventions) associated with the interventions, and the characteristics of AOM
      episodes that the child would experience without any intervention. RESULTS:
      Thirty-seven parents with young children were interviewed for this project. The
      preferred intervention for a child was sensitive to the number of episodes of AOM
      the child was anticipated to have in the coming year, the percentage of these
      episodes predicted to be severe, and how parents rated tympanostomy tubes
      compared with prophylactic antibiotics. In our base case of four episodes of AOM
      in the coming year (two mild episodes and two severe episodes), we found that
      tympanostomy tubes resulted in the best average outcome. Under different patient
      conditions, however, the preferred strategy could be either the use of
      prophylactic antibiotics or watchful waiting. CONCLUSIONS: In our base case, the
      model suggested that tympanostomy tubes were preferable to prophylactic
      antibiotics. However, there is no single preferred preventive intervention for
      all children with recurrent AOM because of variation in the character of
      infections and the values parents give to the potential outcomes.

PMID- 9564373
TI  - Patient-centered clinical decisions and their impact on physician adherence to
      clinical guidelines.
AB  - BACKGROUND: This study was undertaken to assess the impact of traditionally
      unmeasured patient-centered factors on primary care physicians' decisions to
      adhere to an evidence-based clinical practice guideline for heart failure.
      METHODS: Experimental and control scenarios were developed to test three patient
      centered factors hypothesized to influence physician nonadherence to a heart
      failure guideline: patient concerns about finances, quality of life, and location
      of care. Each factor represented an implicit patient goal potentially in conflict
      with a goal of the guideline recommendations. A control scenario for one factor
      and an experimental scenario for a second were placed within a cross-sectional
      survey and questionnaires were mailed by random assignment to 978 Upstate New
      York family physicians. Experimental and control responses were compared by chi
      square. RESULTS: The response rate was 47% (n = 456). Each hypothetical patient
      centered factor resulted in significant reductions in physicians' predicted
      adherence. Reductions in reported pharmaceutical usage and testing of left
      ventricular (LV) function were associated with patient financial difficulties (P
      < .01). The poor quality-of-life scenario was associated with reduced testing for
      LV function but increased discussion of advance directives (P < .01). The
      clinical scenario limiting access to services for a rural patient was associated
      with decreases in physician choice of LV function tests and cardiology referrals
      (P < .05). CONCLUSIONS: Patient-specific factors are associated with physician
      decisions to comply with guideline recommendations. These findings suggest that
      performance profiles measuring physician adherence to guidelines should be
      interpreted with caution, and that current case-mix methodologies may not
      adequately control for patient-centered factors that may influence health care
      quality.

PMID- 9564374
TI  - The influence of CLIA '88 on physician office laboratories.
AB  - BACKGROUND: The study objectives were to examine the influence of the Clinical
      Laboratory Improvement Amendments of 1988 (CLIA '88) on laboratory testing
      activities in physician offices, and to identify relationships between the
      characteristics of practices and their responses to the regulation. METHODS: The
      data come from a 1995 survey of physician office laboratories conducted by
      Mathematica Policy Research, and are supplemented by data from a 1991 laboratory
      survey. Primary care physician practices performing level I and level II tests in
      1991 were resurveyed in 1995. Respondents were asked a series of questions
      pertaining to the types of laboratory tests performed in their offices, and
      whether CLIA '88 had any influence on the decision to change testing practices.
      We present descriptive statistics to examine differences across practices in
      response to CLIA '88. Significant determinants of the decision to drop or modify
      onsite testing activities are identified using multivariate analysis. RESULTS:
      More than 64% of physicians surveyed cited CLIA '88 as a factor in their decision
      to reduce or eliminate in-office testing. The most striking effect of CLIA '88
      appears to be on pediatric practices and practices in rural areas, of which more
      than 70% have reduced or eliminated onsite testing. Where the potential burden of
      compliance is smaller, as in large practices, CLIA '88 has had less impact.
      CONCLUSIONS: CLIA '88 has had significant influence on access to laboratory
      testing services. According to the data from the 1995 survey, almost two thirds
      of physicians have eliminated some or all in-office tests. Of those physicians
      previously conducting in-office tests, 70% have chosen to send patients and
      specimens to outside facilities, resulting in greater inconvenience for patients
      and delays in diagnosis and treatment. These delays, and the potential for
      patient noncompliance stemming from the inconvenience of obtaining tests, have
      serious implications for the quality of medical care.

PMID- 9564375
TI  - Screening for problem drinking: does a single question work?
AB  - BACKGROUND: Brief interventions with problem drinkers have been shown to be
      effective, but physicians often do not ask about alcohol use. If a single
      question could effectively screen for problem drinking, it might facilitate
      intervention with problem drinkers. METHODS: A cross-sectional study was
      undertaken to address the clinical utility of the question, "On any single
      occasion during the past 3 months, have you had more than 5 drinks containing
      alcohol?" Placing it between questions about tobacco and seat-belt use, we
      presented the three questions in writing to 1435 patients; 95.3% answered them.
      With a systematic sample of 101 patients who answered yes and 99 who answered no,
      we administered the Alcohol Use Disorders Identification Test in writing followed
      by two gold-standard interview instruments: (1) a calendar-based review of
      drinking, with at-risk drinking defined as drinking more than 4 drinks on one
      occasion or more than 14 drinks per week for men, and more than 3 drinks on one
      occasion or 7 per week for women; and (2) the alcohol questions in the Composite
      International Diagnostic Interview, with alcohol-use disorders defined by the
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. We
      defined problem drinking as either at-risk drinking in the previous month or an
      alcohol-use disorder in the past 12 months. RESULTS: The single question had a
      positive predictive value of 74% and negative predictive value of 88% for problem
      drinking, with a sensitivity of 62% and a specificity of 93%. The question's
      utility was similar for detecting at-risk drinking and current alcohol-use
      disorders; it correctly identified all 29 patients who had both. CONCLUSIONS: A
      single question about alcohol can detect at-risk drinking and current alcohol-use
      disorders with clinically useful positive and negative predictive values.

PMID- 9564377
TI  - Nurse practitioners: the growing solution in healthcare delivery.

PMID- 9564376
TI  - Implications of acute bronchitis.

PMID- 9564378
TI  - Reformulating nursing in greater Kansas City.

PMID- 9564379
TI  - The visibility of organizational culture in a long-term care facility.
AB  - Our findings suggest that the perceptions of the staff members and families are
      not easily discernible by administrators or outsiders such as family members.
      This inability to judge important changes in the culture of an organization has
      important consequences for management. If administrators cannot tell which groups
      perform in the desired direction, they are not in a position to reward and
      reinforce desired behaviors. If cultural changes are necessary prerequisites to
      ensure organizational survival, how will an organization be able to create and
      maintain changes in the culture if there is no prevailing culture that is visible
      or public to others? More importantly, how will an organization be able to create
      a visible culture to others if management does not agree on what constitutes
      successful change? Nursing leaders who understand organizational culture concepts
      will be in a better position to influence the successful outcome of
      organizational change.

PMID- 9564380
TI  - Caution: the danger of taking 'interdisciplinary' to the extreme.

PMID- 9564381
TI  - Organizational redesign. Changing educational needs of midlevel nurse
      administrators.

PMID- 9564382
TI  - From independence to interdependence. Creating synergistic healthcare teams.
AB  - As the structure of healthcare institutions changes, nurse administrators
      frequently are being called on to lead interdisciplinary programs. To be
      successful in this new health paradigm, teams must strive to create total
      stakeholder satisfaction by adopting a mindset that work is interdependent, not
      independent, and then striving to work synergistically. The author presents 12
      themes that emerged from a study investigating the essential elements of
      synergistic team relationships.

PMID- 9564383
TI  - An organization-wide approach for an effective communication system, Part 2.
AB  - This is the second article in a two-part series that describes an organization's
      approach to designing, implementing, and evaluating a communication system. Part
      1 of this series, published in the March 1998 issue, focused on the design and
      implementation of this system. This article addresses the evaluation of outcomes
      related to identified goals to improve communication flow and decision making on
      multiple levels and to promote accountability for clinical and operational
      performance. Implementation strategies involving change management, emergence of
      issues with related implications, and planned evolution of this system also are
      discussed for ongoing organizational performance improvement.

PMID- 9564384
TI  - A cultural transformation model for nursing.
AB  - The rapidity and constancy of change, coupled with a culture of staff entitlement
      and passive and defensive leadership behaviors, prompted the development of an
      intensive plan for cultural transformation. The cultural transformation steps of
      leadership development, nominal group technique, quality improvement teams, and
      evaluation process are explored in detail. Lessons learned and outcomes obtained
      within the first 6 months after implementation are identified.

PMID- 9564385
TI  - The effectiveness of inpatient case management. Fact or fiction?
AB  - Production processes and service delivery in acute care hospitals can be
      fragmented. Inpatient case management has the potential to improve both processes
      and outcomes of hospital care. The author reports on 18 research studies that
      used inpatient case management as the treatment variable. These outcome studies,
      using case management, did not provide the evidence needed to address
      deficiencies in inpatient settings. However, these studies do provide clear
      direction for nurse administrators and nurse researchers to take concerning the
      next steps needed to address this critical issue.

PMID- 9564386
TI  - Managerial partnerships. The wave of the future?
AB  - Although managerial partnerships are becoming more common in healthcare
      organizations, very little is available in the literature regarding a practical,
      concrete methodology for ensuring success of the relationship. The authors
      explore the nature of managerial partnerships and the perils and pitfalls of
      forming these relationships. Experiences from successful and failing partnerships
      will be used to identify the essential elements of healthy partnerships. Key
      steps and principles for creating a successful partnership are identified.

PMID- 9564387
TI  - Education in administration. Trends in MSN/MBA and MSN in nursing administration.
AB  - Avenues for the preparation of nurses who wish to pursue administrative careers
      continue to be debated. The author reports changes in the numbers and enrollments
      of master of science in nursing/master of business administration (MSN/MBA)
      programs as well as trends in MSN in nursing administration programs since 1993.
      Respondents to a survey of all U.S. nursing graduate programs indicated that both
      types of programs have undergone substantial changes on a variety of measures.
      The author considers these results in suggestions for building new approaches to
      administrative preparation.

PMID- 9564388
TI  - Palliative care.

PMID- 9564389
TI  - The Oxford Vaporizer.

PMID- 9564390
TI  - Intrathecal pethidine: pharmacology and clinical applications.
AB  - Pethidine is the only member of the opioid family that has clinically important
      local anaesthetic activity in the dose range normally used for analgesia.
      Pethidine is unique as the only opioid in current use that is effective as the
      sole agent for spinal anaesthesia. In lower doses, intrathecal pethidine is also
      an effective analgesic for treating pain in labour. This paper reviews the
      pharmacology of intrathecal pethidine and clinical experience reported to date.
      Articles reviewed include those identified by a Medline search using keywords
      "intrathecal" or "spinal anaesthesia/ anesthesia" and "pethidine" or
      "meperidine". Reference lists from identified papers were scrutinized to identify
      further relevant articles.

PMID- 9564391
TI  - Subcutaneous tunnelling of epidural catheters for postoperative analgesia to
      prevent accidental dislodgement: a randomized controlled trial.
AB  - The use of subcutaneous tunnelling to prevent movement of epidural catheters was
      examined in a prospective controlled trial. There were 113 patients in the
      standard group and 100 in the tunnelled group. The groups were similar with
      respect to age, sex and weight. There were 176 thoracic catheters, and 37 lumbar
      catheters. Mean duration of catheterization in the tunnelled group was 3.5 +/-
      1.3 days and in the standard group, 3.1 +/- 1.5 days. In total, 60 catheters
      moved significantly from their initial position: 17 (28%) moved inwards and 43
      (72%) moved outwards. 159 catheters were still functioning at the time of their
      removal, 76 standard and 83 tunnelled. This represents 67 and 83% of the two
      groups respectively. Subcutaneous tunnelling was shown to prevent clinically
      significant inwards (P = 0.043) and outwards (P = 0.0005) movement of epidural
      catheters and is more likely to result in a functional epidural blockade at the
      time of catheter removal (P = 0.0084).

PMID- 9564392
TI  - Postoperative nausea and vomiting: development of a management protocol.
AB  - Postoperative nausea and vomiting (PONV) is still an important and common
      problem. Despite the introduction of new antiemetic drugs, the management of PONV
      remains difficult. In this article we describe the development and evaluation of
      a management protocol for PONV, which consists of a treatment algorithm
      accompanied by a nursing education program. Implementation of this management
      protocol has been well-accepted by staff, appears to have reduced delay in
      patient treatment and improved patient care, and has significantly reduced staff
      workload. It is planned to use continuous quality improvement techniques to
      further refine the algorithm and continue assessment of its efficacy and of
      patient satisfaction.

PMID- 9564393
TI  - Patient evaluation and comparison of the recovery profile between propofol and
      thiopentone as induction agents in day surgery.
AB  - The patient's subjective perception of the quality of his/her recovery after day
      case anaesthesia with propofol or thiopentone as induction agents is still
      controversial. The authors investigated the perception and quality of awakening
      after anaesthesia during the recovery period and at 24 hours and 72 hours, in
      outpatients undergoing anaesthesia induced either with propofol or thiopentone
      and maintained with a volatile anaesthetic. In a double-blind study in adults
      undergoing knee arthroscopy in a day surgery unit, propofol and thiopentone were
      compared as induction agents in 60 randomized outpatients. A Critical Flicker
      Fusion Threshold test (CFFT), verbal test for anxiety, visual analog scale for
      anxiety and pain, and questionnaires were used to assess objectively and
      subjectively the quality of anaesthesia and awakening during the postoperative
      period. Demographic data and mean duration of anaesthesia were similar. In the
      propofol group, patients awoke more rapidly (9.2 +/- 5.8 vs 12.3 +/- 5.8 min) (P
      < 0.05); however, the CFFT measurements did not show any significant difference
      between the groups, except at time = 0 min, when 17 patients in the propofol
      group were able to perform the test versus only 10 patients in the thiopentone
      group (P < 0.05). At 4, 24, and 72 hours postoperatively, the authors were unable
      to detect any difference between the two groups. Except for early recovery, there
      were no differences between the intermediate and late recovery profiles, when
      propofol or thiopentone was used as the anaesthetic induction agent in day
      surgery.

PMID- 9564394
TI  - Contamination of propofol infusions in the intensive care unit: incidence and
      clinical significance.
AB  - Epidemics of bacteraemia and wound infection have been associated with the
      infusion of bacterially contaminated propofol administered during anaesthesia. We
      conducted an observational study to determine the incidence and clinical
      significance of administration of potentially contaminated propofol to patients
      in an ICU setting. One hundred patients received a total of 302 infusions of
      propofol. Eighteen episodes of possible contamination of propofol syringes were
      identified, but in all cases contamination was by a low-grade virulence pathogen.
      There were no episodes of clinical infection or colonization which could be
      attributed to the administration of contaminated propofol. During the routine use
      of propofol to provide sedation in ICU patients the risk of nosocomial infection
      secondary to contamination of propofol is extremely low.

PMID- 9564395
TI  - Epidural analgesia: prospective audit of 1062 patients.
AB  - A prospective survey of one thousand and sixty-two patients receiving epidural
      analgesia in surgical wards was undertaken over a two-year period. The duration
      of infusion ranged from one to fourteen days, with a mode of three days. There
      were 1131 episodes where a local anaesthetic and opioid mixture was used and 160
      where opioids were used alone. Local anaesthetic was not used without opioids.
      23% of catheters were removed prematurely because of catheter related problems
      including accidental dislodgement (13%) and skin site inflammation (5.3%). No
      epidural abscess or haematoma was identified. In 14% of the total number of
      episodes there was either no demonstrable block or complications occurred
      requiring a change of solution: 30% of this group were salvaged following
      intervention by the Acute Pain Service (APS). The incidence of respiratory
      depression was 0.24%. There was no case of delayed respiratory depression.
      Epidural analgesia can be used safely in surgical wards provided that regular
      review of the patients is undertaken. It must be anticipated however, that up to
      20% of patients will not receive adequate analgesia for the first 48 hours
      postoperatively. The failure rate could be halved if accidental dislodgement of
      epidural catheters could be eliminated.

PMID- 9564396
TI  - Comfort and safety in eye surgery under local anaesthesia.
AB  - The study consisted of two parts: 1. The standard system in use at our hospital
      for gas delivery under the drapes during eye surgery under local anaesthesia was
      compared with one incorporating a venturi. 2. The oxygen concentration at the
      operation site was measured with three methods of draping using the two systems.
      Twenty-three patients and thirty-one volunteers from the operating room staff
      were subjected to operating conditions and gas concentrations and certain vital
      signs measured using both systems. The subjective response of the volunteers,
      none of whom had blocks or premedication, was noted. The burden of rebreathing
      seen with a significant proportion of cases using 6 l/min of fresh gas flow was
      not seen when the venturi system was used. The safety from fire hazard using 26%
      oxygen and diathermy was demonstrated with occlusive and free draping.

PMID- 9564397
TI  - Anaesthesia circuits, humidity output, and mucociliary structure and function.
AB  - We compared the effects of humidity delivered by the circle system at low fresh
      gas flows (FGF) with a conventional two-limb and coaxial circuit on the structure
      and function of the tracheobronchial epithelium in dogs. Animals were
      anaesthetized and mechanically ventilated using an anaesthesia ventilator to
      maintain normocarbia. Group I (control) animals received a FGF equal to the
      required minute ventilation mimicking an open circuit technique. Group II and III
      animals had FGF set at 20% of the required minute ventilation. Group II used a
      two-limb circuit and Group III used a coaxial circuit. Relative humidity and
      temperature of inspired gases were measured at baseline and hourly afterwards. In
      the first experiment, biopsies of the tracheobronchial tree were obtained
      bronchoscopically at baseline and then hourly for six hours. Microscopic
      examination of these samples allowed calculation of mean ciliary length. In the
      second experiment, tracheal mucus flow velocity (TMFV) was measured at baseline
      and hourly afterward, using a cinebroncho-fibrescopic method. Delivered absolute
      humidity was greatest with low FGF and the coaxial circuit, followed by low FGF
      and a conventional circuit, and high FGF (15 +/- 1.4 vs 9 +/- 0.8 vs 5 +/- 0.4 mg
      H2O, P < 0.01) after two hours. Mean cilia length (micron) and TMFV (mm/min) fell
      during the first hour in all three groups. At hour two TMFV returned to baseline
      in Group III and was significantly greater than Groups I and II (0.8 +/- 0.4 vs
      8.6 +/- 1.1 vs 15.4 +/- 2.1, P < 0.001). Mean ciliary length demonstrated a
      similar pattern with reductions from baseline in all three groups for the first
      two hours. Groups II and III had an increase in cilia length beginning at hour
      three and were both significantly greater than Group I at hours 3 through 6 (1.3
      +/- 0.5 vs 3.2 +/- 1.1 vs 4.2 +/- 0.8, P < 0.001). Alterations in
      tracheobronchial structure and function result from exposure to dry gases and are
      amplified by the duration of exposure. Our findings suggest a minimum of 12 to 15
      mg H2O/l is necessary to prevent these alterations. In this study, the
      combination of low FGF and a coaxial anaesthesia circuit reached this minimum
      threshold more quickly than a conventional two-limb circuit.

PMID- 9564398
TI  - Evaluation of a lactate sensor for rapid repeated measurements of blood lactate
      concentration.
AB  - In critically ill patients, serial measurements of blood lactate may indicate
      adequacy of therapy and predict development of multi-organ failure. We studied
      the accuracy, precision, and repeatability of the newly developed 800 Series
      Lactate Sensor (Ciba Corning Diagnostic Corp., Medfield, U.S.A.). Lactate levels
      determined with the sensor were compared with the standard laboratory method
      (Abbott TDX) in 75 paired arterial blood samples from 20 patients. Agreement
      between methods was determined and the mean coefficient of variation calculated
      for repeated measurements. The bias of the sensor was -0.38 mmol/l (CI -0.23 to 
      0.53), and the precision +/- 0.67. The coefficient of variation for repeated
      measurements was 1.95% with the sensor, and 11.5% with the TDX (P = 0.007). The
      new sensor offers a more reproducible, rapid method of measuring lactate, vital
      for serial measurements. The relatively wide limits of agreement between the
      methods reflect the greater variability of the TDX assay.

PMID- 9564399
TI  - Box Hill Hospital resuscitation trolley.
AB  - A resuscitation trolley has been designed to meet the following requirements.
      Continuous oxygen supply from the trolley for the duration of the emergency;
      medical suction of similar strength to that of an ICU treatment bay and provision
      of equipment and drugs in a modular form, which is uniform across the
      institution, and which allows immediate replacement from stock. These
      requirements have been fulfilled whilst maintaining a total trolley weight and
      manoeuvrability similar to that of commercially manufactured trolleys available
      in Australia.

PMID- 9564400
TI  - Performance of the Atom 235 syringe infusion pump under hyperbaric conditions.
AB  - Inotrope-dependent patients may become haemodynamically unstable during treatment
      in the hyperbaric chamber. One possible cause is altered performance of infusion
      devices. We tested six Atom 235 syringe infusion pumps under hyperbaric
      conditions of 2.8 atmospheres absolute in a multiplace chamber using a
      gravimetric method. There was a small but significant reduction in infused volume
      during a thirty-minute period including compression time. We concluded that
      altered inotrope delivery may explain at least some of the haemodynamic
      instability sometimes seen, although a physiologic effect of hyperbaric treatment
      cannot be excluded.

PMID- 9564401
TI  - The preoperative management of phaeochromocytoma.
AB  - Although the preoperative use of alpha-receptor antagonist drugs is generally
      accepted for patients with phaeochromocytoma, evidence on the most appropriate
      treatment and its timing is scarce. In this retrospective study, the
      effectiveness of the preoperative preparation of fourteen patients who required
      surgical excision of a phaeochromocytoma was examined in the light of their
      operative stability. A simple score was developed of blood pressure stability by
      scoring the need for additional antihypertensive agents intraoperatively before,
      and blood pressure support after, tumour removal. A higher score indicated
      greater instability. Twelve patients received phenoxybenzamine and their
      stability was superior to the two patients treated with labetalol and with
      prazosin. There was no correlation between the duration of treatment with
      phenoxybenzamine and the operative stability (r = 0.18 P = 0.55 Spearman). The
      five patients who were treated with phenoxybenzamine for longer than 10 days did
      not have better perioperative blood pressure stability than the five patients who
      had treatment for less than a week. Predictive factors for intra-operative blood
      pressure stability were also sought. The degree of postural hypotension after
      treatment with phenoxybenzamine did not predict operative stability (r = -0.31, P
      = 0.33 Spearman). However, the peak total catecholamine level found during
      surgery correlated quite well with more operative instability (r = 0.65, P =
      0.031, Spearman), suggesting that patients with phaeochromocytomas with high
      production of catecholamines are more likely to show cardiovascular instability.

PMID- 9564402
TI  - Undergraduate education in anaesthesia: the influence of role models on skills
      learnt and career choice.
AB  - Undergraduate teaching of anaesthesia occurs in about two-thirds of Australian
      departments of anaesthesia: however, student contact hours are limited compared
      with those of other disciplines. Seventy-five directors of anaesthesia were
      surveyed by written questionnaire concerning the time devoted in their department
      to undergraduate study and teaching of practice/skills to undergraduate students
      (40 responded). One hundred and sixty final year students were surveyed regarding
      career choice, anaesthesia skills taught them and role models identified during
      their training (101 responded). Most final year students had been taught and had
      learnt the basic skills of life support such as bag and mask ventilation,
      cardiopulmonary resuscitation and intravenous cannulation. However, fewer were
      taught more specialized skills such as induction of anaesthesia and spinal
      anaesthesia. Positive role models in teaching anaesthetists were identified by
      66% of students, more commonly if they were taught advanced skills, and were
      significantly associated with satisfaction with theoretical and practical
      training. For those students intending a career in anaesthesia (18%), 94%
      identified a positive role model compared to 65% who did not (P = 0.03).

PMID- 9564403
TI  - Central nervous system toxicity attributable to epidural ropivacaine
      hydrochloride.
AB  - Ropivacaine, a new local anaesthetic agent, has been demonstrated to have less
      potential than bupivacaine for central nervous system toxicity on the basis of
      human and animal studies. We report a case of a convulsion secondary to presumed
      inadvertent intravascular injection of 20 mg of ropivacaine in a 44 kg patient
      during an epidural for chronic pain. There were minimal signs of cardiovascular
      toxicity.

PMID- 9564404
TI  - Oxygen contamination of the nitrous oxide pipeline supply.
AB  - Midogas (CIG Australia) nitrous oxide/oxygen blenders are commonly used in
      delivery wards in Australia. In this case report we describe an incident where a
      small hole in the diaphragm of the oxygen failure alarm in a Midogas nitrous
      oxide/oxygen blender led to retrograde flow of oxygen contaminating the nitrous
      oxide pipeline supply to the operating theatres and the delivery ward. This
      caused a reduced level of nitrous oxide to the patient in theatre, but there was
      no adverse outcome. However, if the oxygen pipeline pressure had been lower than
      the nitrous oxide pipeline pressure, the contamination would have been reversed,
      potentially resulting in a hypoxic mixture being delivered to many patients.
      Suggestions are made as to a method of prevention of this problem.

PMID- 9564405
TI  - Remifentanil and propofol total intravenous anaesthesia for thymectomy in
      myasthenia gravis.
AB  - We report a case of trans-sternal thymectomy for myasthenia gravis using a non
      relaxant, total intravenous technique with propofol and remifentanil. This
      afforded excellent control of heart rate and pressor responses during surgery
      while allowing early return of spontaneous ventilation and extubation within nine
      minutes of termination of anaesthesia. Advantages and disadvantages of this
      approach versus relaxant and volatile techniques are discussed with particular
      reference to preservation of neuromuscular function.

PMID- 9564406
TI  - Pulmonary aspiration of blood following traumatic laryngeal mask airway
      insertion.
AB  - An unusual and potentially life-threatening complication arising from a
      relatively common event--bleeding due to traumatic laryngeal mask insertion--is
      presented. It demonstrates that the laryngeal mask airway (LMA) cannot always be
      relied upon to protect the lower airway from upper airway bleeding.

PMID- 9564407
TI  - Functional upper airway obstruction.
AB  - Functional disorders of the vocal cords can present with acute, dramatic upper
      airway obstruction, with features mimicking asthma or functional dysphonia. We
      report the case of an eighteen-year-old female with acute airway obstruction
      initially misdiagnosed as asthma. Laryngoscopy, bronchoscopy and psychiatric
      assessment confirmed a diagnosis of functional disorder of the vocal cords.
      Although a diagnosis of exclusion, it must be borne in mind in order to reduce
      unnecessary medical therapy and surgical intervention. It is only with the
      correct diagnosis that patients can receive appropriate therapy.

PMID- 9564408
TI  - Breathing system filters and hepatitis C.

PMID- 9564410
TI  - Backflow in oxygen tubing.

PMID- 9564409
TI  - Breathing system filters and hepatitis C.

PMID- 9564411
TI  - Nebulized 10% lignocaine for awake fibreoptic intubation.

PMID- 9564412
TI  - Reusable Robertshaw tube.

PMID- 9564413
TI  - Droperidol and dysphoria.

PMID- 9564414
TI  - Clearing the airway--mouth gags, wedges and openers.

PMID- 9564415
TI  - Facilitated nasotracheal intubation.

PMID- 9564416
TI  - The value of information and the cost of uncertainty: who pays the bill?

PMID- 9564417
TI  - The relationship of philosophy, science, and art.

PMID- 9564418
TI  - Class II division 2 skeletal pattern.

PMID- 9564419
TI  - Occlusal traits and perception of orthodontic need in eighth grade students.
AB  - In 1994, 1155 eight-grade students in Alachua County, Fla., were asked about self
      perception of and level of concern for their occlusal status. Clinical
      assessments of orthodontic parameters were also recorded. Twenty-five percent of
      the students had a history of orthodontic treatment. Of the remaining students
      who had no history of orthodontic treatment, 74% reported satisfaction with the
      way their teeth looked, 64% expressed no perceived need for braces, and 57% were
      judged clinically to have optional or no orthodontic needs. Sex, soft tissue
      profile, overjet, anterior crowding, and molar classification were significantly
      associated with the perception of need for braces while race and overbite were
      not. Clinical judgment of orthodontic need differed significantly among levels of
      satisfaction with teeth. Eighth graders with no history of orthodontic treatment
      were generally satisfied with the appearance of their teeth and perceived less
      need for braces than clinicians.

PMID- 9564420
TI  - Orthodontists' assessment and management of patient compliance.
AB  - This study was designed to evaluate the use of predictors and methods of
      improving patient compliance. A survey of 118 items was developed by searching
      the literature for items that other researchers have found to be significant. The
      new questionnaire contained six sections. Sections 1 and 2 pertained to
      predictors of patient compliance; sections 3 and 4 related to methods of
      improving compliance. In section 5, the respondents were asked to evaluate
      patient personality traits that might be important in evaluating compliance, and
      in the last section, demographic background information on the respondents was
      collected. Questionnaires were mailed to 1,262 practicing orthodontists in the
      United States, and 429 responses were received. Patient-related items, such as
      desire for treatment and relationship with parents, were ranked as important
      factors motivating patients to comply. Verbal praise and communication were rated
      as important methods for improving compliance. Personality traits that
      orthodontists found to be predictive of patient compliance were: high self
      esteem; obedient; accommodating; and self-confident. Patients' perceptions of
      their malocclusions, combined with their desire for orthodontic treatment, may be
      good indicators of compliance. Doctor-patient rapport and verbal praise may be
      useful ways to improve compliance.

PMID- 9564421
TI  - Effect of behavior modification on patient compliance in orthodontics.
AB  - The purpose of this study was to evaluate the effects of a reward system for
      improving patient compliance in orthodontic treatment. The sample consisted of
      144 orthodontic patients (63 male, 81 female, average age 12.8 years), 6 to 12
      months into their treatment. The sample was divided into above-average and below
      average compliers, based on the orthodontic patient cooperation scale (OPCS).
      Each group was further divided into three subgroups: (a) a control group, which
      received only standard instructions; (b) an award group, which received
      compliance instructions and a written evaluation of compliance; and (c) a reward
      group, which received compliance instructions, a report card, and eligibility to
      receive rewards for adherent behavior. Two measurements of patient compliance
      were used: (1) the OPCS, which divided the sample into high and low compliers and
      was used to compare compliance before and after the 6-month experimental period;
      and (2) a clinical evaluation of compliance that was based on oral hygiene,
      appointment punctuality, appliance wear, and appliance maintenance. Evaluations
      were completed at each monthly appointment. Average compliance scores of above
      average compliers showed no significant improvement with rewards. The average
      scores of patients with below-average compliance did not improve significantly.
      Only oral hygiene scores in the low compliance reward group were better than in
      the low compliance control group. Academic performance in school was found to be
      correlated (p < 0.001) with compliance. Above-average compliers remained above
      average in their compliance. The award/reward system may help motivate below
      average compliers to comply with prescribed instructions.

PMID- 9564422
TI  - The use of tooth thickness in predicting intermaxillary tooth-size discrepancies.
AB  - Intermaxillary tooth-size discrepancies can be assessed using a diagnostic setup
      or predicted using a mathematical formula, such as the Bolton analysis. However,
      variations in tooth thickness may produce inaccuracies in the Bolton analysis
      ratio. To date, no method for incorporating tooth thickness into discrepancy
      prediction has been proposed. The purpose of this study was to design and test a
      new method of predicting anterior tooth-size discrepancy that takes into account
      tooth thickness and width. Forty-four positioner setup models were set to ideal
      overbite (2.5 mm) and occlusion (Class I canine relationship). Interproximal gaps
      between the maxillary or mandibular central incisors were allowed in order to
      optimize tip and torque. The mesiodistal width of all anterior teeth and the
      labiolingual thickness of the maxillary incisors were measured on these idealized
      setups to the nearest 0.1 mm. Actual intermaxillary anterior ratios were then
      calculated. A new method of prediction was developed by assuming a linear
      relationship between tooth thickness and ideal intermaxillary ratio. Errors in
      Bolton's method were compared with the new method. The results showed wide
      variations in mesiodistal tooth widths, tooth thicknesses, and intermaxillary
      anterior ratios in orthodontically treated patients. The correlation coefficient
      between the intermaxillary ratio and tooth thickness was r = 0.68 when tooth
      thickness was < 2.75 mm, and r = 0.28 when tooth thickness was > or = 2.75 mm.
      The mean absolute errors in predicting the actual intermaxillary ideal ratio was
      1.29 +/- 0.81 for Bolton's ratio and 0.84 +/- 0.46 for the new prediction
      formula. These new formulas were better than Bolton's ratio in predicting tooth
      size discrepancies (p = 0.003). Tooth thickness combined with mesiodistal width
      may be useful in predicting intermaxillary tooth-size discrepancies.

PMID- 9564423
TI  - Enamel thickness of the posterior dentition: its implications for nonextraction
      treatment.
AB  - This study describes mesial and distal enamel thickness of the permanent
      posterior mandibular dentition. The sample comprised 98 Caucasian adults (59
      males, 39 females) 20 to 35 years old. Bitewing radiographs of the right
      permanent mandibular premolars and first and second molars were illuminated and
      transferred to a computer at a fixed magnification via a video camera. Enamel and
      dentin thicknesses were identified and digitized on the plane representing the
      maximum mesiodistal diameter of each tooth. The results showed that there were no
      significant sex differences in either mesial or distal enamel thickness. Enamel
      on the second molars was significantly thicker (0.3 to 0.4 mm) than enamel on the
      premolars. Distal enamel was significantly thicker than mesial enamel. There was
      approximately 10 mm of total enamel on the four teeth combined. Assuming 50%
      enamel reduction, the premolars and molars should provide 9.8 mm of additional
      space for realignment of mandibular teeth.

PMID- 9564424
TI  - Eruption and function of maxillary third molars after extraction of second
      molars.
AB  - After extraction of maxillary second molars, will the third molars erupt into a
      functional position in a timely manner? To answer this question, 56 consecutively
      treated cases of maxillary second molar extraction were reviewed. The unerupted
      positions of the maxillary third molars were measured on cephalometric
      radiographs, ages of eruption were evaluated, positions of erupted third molars
      analyzed, and interproximal periodontal health of adjacent first molars compared.
      The results showed that, generally, the eruption of third molars was accelerated.
      Most of the third molars had acceptable interarch and intra-arch occlusal
      relationships. The interproximal periodontal health of the third molars was
      similar to that of adjacent first molars. Most maxillary third molars will
      successfully erupt into an acceptable position by the late teens.

PMID- 9564425
TI  - Ectopic eruption of the first permanent molars: prevalence and etiologic factors.
AB  - The purpose of this research was to study the prevalence of ectopic eruption of
      the first permanent molars and possible etiologic factors. A group of 4,232 Thai
      students, from 6 to 9 years old, was examined. The prevalence of ectopic eruption
      of the first permanent molars in the subjects was 0.75%. Both the severity of the
      ectopic eruption and the amount of root resorption on the second primary molars
      were more pronounced in the maxilla than in the mandible. The important etiologic
      factors were the eruption path of the first permanent molars relative to
      reference lines and the size of the mandibular second primary molars. The amount
      of proximal caries did not seem to affect the prevalence of ectopic eruption.

PMID- 9564426
TI  - Hyalinization and root resorption during early orthodontic tooth movement in
      adolescents.
AB  - The aim of this investigation was to study the hyalinization of the periodontal
      ligament with time and its relationship to root surface resorption after the
      application of an orthodontic force, reactivated weekly, of 50 cN (approximately
      50 g). Fifty-six patients (18 boys and 38 girls, mean age 13.8 years) were
      divided into 7 groups of 8. In each patient, one premolar was moved buccally 161
      with a fixed orthodontic appliance. The contralateral premolar served as a
      control. The experimental periods ranged from 1 to 7 weeks. Local areas of
      overcompression in the periodontal ligament were recorded in 33 test teeth (59%)
      and 2 controls (4%). Hyalinization was seen in all experimental groups, more
      often after the first 4 weeks of force application. Hyalinized areas were
      recorded opposite an intact root surface (54%) or close to and just apical or
      coronal to an area of root resorption (45%), and were usually located
      buccocervically and linguoapically, corresponding to expected pressure zones of
      the periodonal ligament.

PMID- 9564427
TI  - Periodontal conditions following surgical and orthodontic treatment of palatally
      impacted maxillary canines--a follow-up study.
AB  - This follow-up study reports on the periodontal status 1 to 18 years after the
      completion of orthodontic treatment of unilateral palatally impacted maxillary
      canines and their adjacent incisors and premolars. Registrations were performed
      on 42 patients, 19 to 59 years old (mean 35 years) at investigation. An
      orthodontic pin with eyelet had been placed after exploration of the canine and,
      in some cases, bone removal. A flap had been raised and resutured after bone
      removal in 11 cases. The results showed greater mesial probing depth of the
      canines on the treated side, on the adjacent lateral incisors distolingually, and
      on the first premolars mesiolingually. Marginal bone level was found to be lower
      on the distal aspect of the treated canines and adjacent laterals. In general,
      the results showed a good gingival and periodontal status with slight differences
      between treated and untreated sides.

PMID- 9564428
TI  - Uprighting mesially impacted mandibular permanent second molars.
AB  - Impaction of permanent teeth is a relatively common occurrence and can involve
      any tooth in the dental arch. Impacted mandibular second molars are relatively
      rare, but when they occur they may present a clinical problem for the
      orthodontist and oral surgeon. A typical case of bilaterally impacted mandibular
      second molars is illustrated, with orthodontic and surgical treatment options
      presented. Emphasis is placed on early diagnosis and initiation of corrective
      orthodontic therapy.

PMID- 9564429
TI  - Case report: forced eruption and implant site development.
AB  - It is now possible to use the orthodontic extrusion of periodontally compromised
      teeth to facilitate the development of a future implant site in an area where the
      amount of bone in the inciso-apical dimension would otherwise have been
      inadequate. The purpose of this case report was to analyze the hard and soft
      tissue changes when forced eruption is used for implant site development.

PMID- 9564430
TI  - Case report: management of significant incisor root resorption associated with
      maxillary canine impaction.
AB  - Orthodontic and periodontic management of a patient with bilaterally impacted
      maxillary canines and advanced resorption of the adjacent lateral incisors is
      presented. In treating the patient, the affected laterals were retained and the
      canines were surgically exposed, then moved away from the roots of the laterals
      and into position in the arch. Alternative treatment strategies are discussed.
      Long-term follow-up evaluation revealed successful maintenance of the dentition
      and of periodontal health.

PMID- 9564431
TI  - Demonstration of a method to characterize and develop airway access devices for
      total liquid ventilation.
AB  - Devices are being developed to carry out perfluorocarbon total liquid ventilation
      (TLV) in adult-sized animals or patients. A limiting factor in the clinical
      application of TLV lies in the ability to administer adequate tidal volumes of
      oxygenated perfluorocarbon through airway access devices. A single number, the M
      number, is demonstrated in this paper as a systematic method for ranking the flow
      characteristics of currently available airway access devices, such as
      endotracheal or tracheostomy tubes, and for designing new airway access devices
      exclusively for TLV. The M-number of several commonly used endotracheal and
      tracheostomy tubes is determined as a demonstration of the use of the M-number.
      Two nomograms are presented based on the M-number, and a description for their
      use in the clinical and laboratory settings is given.

PMID- 9564432
TI  - Hemoglobin based oxygen carriers: how much methemoglobin is too much?
AB  - The oxidized form of hemoglobin, methemoglobin, is unable to deliver oxygen to
      tissues. Hemoglobin based oxygen carriers generally lack the natural oxidative
      reductive machinery present within the red blood cell that converts methemoglobin
      to hemoglobin. This study examines tolerable levels of methemoglobin that can be
      present in solutions of polyethylene glycol (PEG) conjugated bovine hemoglobin
      without compromising its ability to deliver oxygen. Rodents were exchange
      transfused to 30% of their estimated blood volume with solutions of six grams
      percent PEG-hemoglobin containing varying concentrations of PEG-methemoglobin.
      Tissue oxygenation was measured by an oxygen dependant phosphorescence quenching
      method. This study also looked at the level of methemoglobin formation following
      a top loaded infusion of low methemoglobin containing PEG-hemoglobin. Results of
      the oxygenation study showed that PEG-methemoglobin levels at or below 10% did
      not significantly alter the ability of solutions to deliver oxygen to intestines,
      liver, spleen and kidney. However, PEG-methemoglobin levels greater than 10%
      resulted in a significant decrease in PEG-hemoglobin's ability to oxygenate
      tissues. In addition, methemoglobin levels remain low (< 10%) for a substantial
      period of time following PEG-hemoglobin administration.

PMID- 9564433
TI  - Side reaction caused by the perfluorocarbon emulsions in intravenous infusion to
      experimental animals.
AB  - The perfluorocarbon (PFC) emulsions are infusion gas-transporting media and are
      usually called the artificial blood. However anaphylactoid reaction were observed
      during intravenous infusion of PFC emulsions. The cause of side reactions is the
      activation of the complement system. An indirect sign of the intravascular
      activation of the complement is the neutropenic effect in the peripheric blood.
      Taking into consideration the phenomen, the method of evaluation of anaphylactoid
      reaction caused by PFC emulsions has been elaborated using the neutropenic index.
      We evaluated the biocompatibility of 26 PFC emulsions of different composition in
      intravenous infusion to rabbits using this index. Emulsions evoked reactions of
      different extent. Some emulsions did not cause the neutropenic effect at all.
      Results of this work allow to reach conclusion, that influence of PFC emulsions
      on the complement system is explained not only by emulsifying agent proxanol: the
      stability of emulsions in the vascular bed and in the period of storage in frozen
      state is of great importance as well.

PMID- 9564434
TI  - Sustained release of antimicrobial drugs from polyvinylalcohol and gum arabica
      blend matrix.
AB  - Synthetic polymers are widely used in biomedical applications. Polymer blends
      have recently paved their way in this field. An attempt to prepare blend of
      synthetic polymer polyvinylalcohol and natural macromolecule gum arabica is made
      in this paper. Characterization of these blends by NMR, DSC and viscoelastic
      studies reveal preparation of a blend composition with synergistic properties.
      The blend composition with synergistic properties was used to release various
      antimicrobial drugs. The duration and release of the drug depends on the amount
      of drug loaded in the matrix and solubility of the drug in the matrix and release
      medium. The advantage of this system is that the release kinetics of the drug
      from the system can be tailored by adjusting plasticizer, homopolymer and
      crosslinker composition depending on the drug to be released.

PMID- 9564435
TI  - Study of polymerized hemoglobin in experiment.
AB  - Lyophilized polymerized hemoglobin has no group specificity and does not damage
      the kidney after 2 days of storage; its T/2 is 14-16 hours. P50 of solution
      prepared on the hemoglobin basis is 24-28 torr at 37 degrees C and pCO2, 40 torr
      in 0.05 M Tris-buffer, pH 7.4. As was shown in models of hemorrhagic shock in
      dogs, the hemodynamic properties of the solutions is such that it is capable of
      increasing the cardiac output and maintains the arterial pressure at the level
      close to initial one. Analysis of the oxygen expenditure suggests the expediency
      of using the solution in doses of 1 gr/kg of body weight. The increase in oxygen
      capacity of the solutions administered in the said dose is the result of increase
      in the hemoglobin concentration in blood plasma. Contribution of the solution to
      blood oxygen capacity is 12-13%. The solution of lyophilized modified hemoglobin
      can be used for correction of both hemodynamic disorders and decreased oxygen
      delivery to tissues in hemorrhagic shock.

PMID- 9564436
TI  - Stability of perfluorocarbon emulsions and their compatibility with blood serum.
AB  - There is not enough to study of the perfluorocarbon (PFC) emulsions particle size
      only for judgment the question about their stability and quality. It is essential
      to evaluate also the structure alteration of PFC emulsions and their
      compatibility with the blood serum. It was shown that stability of PFC emulsion
      of the same composition depend on the mode of their preparing. The particle size
      of frozen PFC emulsions as a rule does not change at storage and their
      compatibility with blood serum can remain unchanged. However, the integrity of
      particle structure of PFC emulsions may be destroyed at unfreezing. The average
      diameter of PFC emulsion particles may remain unchanged at storage, but the
      compatibility with blood serum may become worse.

PMID- 9564437
TI  - Hemoperfusion through DNA-coated and uncoated synthetic activated charcoals as an
      additive to the bronchial asthma traditional treatment.
AB  - In this study the single session of small-volume (31) direct hemoperfusion (DHP)
      through uncoated (I group, 24 patients) and DNA-coated (II group, 17 patients)
      synthetic activated carbons has been investigated as an additive to the
      traditional medicamental treatment (III group, 22 patients) of the endogenous
      bronchial asthma. Significant amelioration of the main clinical and immunological
      indices in the patients of the I and II group in comparison with those of III
      group was noted. Between two DHP-including treatment modalities
      hemoimmunosorption onto DNA-coated activated charcoal is suggested as better.

PMID- 9564438
TI  - Evaluation of the oxygen delivery ability of PEG-hemoglobin in Sprague-Dawley
      rats during hemodilution.
AB  - Polyethylene glycol (PEG) conjugation allows bovine hemoglobin (Hb) to retain its
      oxygen delivery capability while increasing its plasma expansion capacity. To
      determine whether PEG-Hb's ability to sustain life is due to its oxygen delivery
      capability rather than its plasma expansion capacity, Sprague-Dawley rats were
      exchange-transfused up to an 85% hematocrit reduction with either PEG-Hb, PEG-50%
      methemoglobin (PEG-mHb), PEG-carbon monoxide hemoglobin (PEG-COHb) or PEG-human
      serum albumin (PEG-HSA). Survival and respiratory rates were monitored during the
      exchange transfusion, at five minutes, 24 hours and 48 hours post operative. Rats
      surviving 14 days were evaluated for hematology, blood chemistry and
      histopathology. Rats infused with PEG-Hb had a survival rate of 100% during the
      transfusion and 79% at 24 hours, as compared to 24 hour survival rates of 30% for
      PEG-mHb, and 0% for both PEG-COHb and PEG-HSA. PEG-Hb treated rats that survived
      the 2 week observation period had normal hematological and blood chemistry levels
      and no significant morphological effects. Therefore, this study demonstrates that
      PEG-Hb can sustain life while similar plasma expansion agents with less oxygen
      delivery capability are not as effective.

PMID- 9564439
TI  - Synthesis, physico-chemical and biological properties of crosslinked modified
      hemoglobin.
AB  - Polymer aspects of polycondensation of pyridoxylated hemoglobin with
      glutaraldehyde have been considered. On the basis of the investigation of
      reaction kinetics, the mechanism of chemical crosslinking of hemoglobin molecules
      into oligohemoglobin is proposed. Owing to the statistical character of the
      reaction, the resulting macromolecules are polydisperse with respect to the
      degree of modification of hemoglobin amino groups, and size of oligohemoglobin
      molecules. The formation of hemoglobin oligomers was studied by varying the
      following reaction conditions: pH, the components ratio, and their
      concentrations. It is shown that the net electric charge of the oligohemoglobin
      molecule depends on the terminating agents. However, these agents have no effect
      on the electrophoretic mobility of erythrocytes in oligohemoglobin solutions. The
      efficiency of oxygen transport of these solutions is close to that of human blood
      erythrocytes. Oligohemoglobin circulation in the blood of animals after
      intravenous infusion leads to rapid removal of low molecular weight fractions
      from blood and to the accumulation of high molecular weight fractions in plasma.
      The period of half-release of oligohemoglobin from the organism is 14-16 h.

PMID- 9564440
TI  - Perfluorocarbon emulsions increase transfer of oxygen in plasma from erythrocyte
      to tissues.
AB  - The erythrocyte oxy- and deoxygenation kinetics and the influence of the
      perfluorocarbon emulsions (PFCE) on the blood were studied using the device
      modeling blood circulation in the organism. It was found that a small additive of
      PFCE changed the oxygen transport in the erythrocyte-plasma-tissues. The oxygen
      carrying properties of erythrocytes of PFCE-blood system are differ from ones of
      pure blood.

PMID- 9564441
TI  - A.E. Bennett Research Award. Regulation of serotonin1A, glucocorticoid, and
      mineralocorticoid receptor in rat and human hippocampus: implications for the
      neurobiology of depression.
AB  - BACKGROUND: Disturbances of the limbic-hypothalamic-pituitary-adrenal axis and
      the serotonin system are commonly found in depressive illness. Studying the
      effect of stress on these two neurobiological systems may give us important clues
      into the pathophysiology of affective illness and help us understand how stress
      and mood disorders are related. METHODS: We studied the effect of chronic
      unpredictable stress and antidepressant treatment on serotonin 1A (5-HT1A),
      glucocorticoid (GR), anti mineralocorticoid (MR) receptor levels in rat
      hippocampus, using in situ hybridization and receptor autoradiography. We also
      used in situ hybridization to quantify hippocampal 5-HT1A, GR, and MR messenger
      (mRNA) levels in a small group of suicide victims with a history of depression,
      compared to matched controls (n = 6). RESULTS: We found that rats subjected to
      chronic unpredictable stress showed a significant elevation of basal plasma
      corticosterone compared to nonstressed rats. Chronic stress also caused a
      decrease in 5-HT1A mRNA and binding in the hippocampus. In addition, chronic
      stress produced alterations on the MR/GR mRNA ratio in this same region. The
      decreases in 5-HT1A mRNA and binding, as well as the MR/GR alterations, were
      prevented in animals that received imipramine or desipramine antidepressant
      treatment. Zimelidine was unable to reverse stress-induced increases in
      corticosterone, and was only partially successful in preventing the stress
      induced receptor changes in the hippocampus. Suicide victims with a history of
      depression showed changes that were very similar to the changes found in chronic
      stress. CONCLUSIONS: Alterations in hippocampal 5-HT1A levels and in the MR/GR
      balance may be one of the mechanisms by which stress may trigger and/or maintain
      depressive episodes.

PMID- 9564443
TI  - Prefrontal and cerebellar abnormalities in major depression: evidence from
      oculomotor studies.
AB  - BACKGROUND: Neurobehavioral studies have identified multiple cognitive and motor
      system disturbances in depressed patients. Neuroimaging studies have identified
      abnormalities in neocortex, striatum, and cerebellar vermis that are probable
      causes of these impairments. METHODS: To further clarify the origins of motor and
      cognitive disturbances in major depression, unmedicated depressed inpatients (n =
      29) and an age- and gendermatched healthy comparison group (n = 19) were tested
      with a battery of oculomotor tasks selected to assess the functional integrity of
      frontostriatal circuitry and the cerebellar vermis. RESULTS: Depressed patients
      demonstrated increased rates of response suppression errors on an antisaccade
      task, less accurate memory for spatial location information in a spatial delayed
      response task, dysmetric visually guided saccades, and increased rates of
      saccadic intrusions during visual fixation. CONCLUSIONS: These results provide
      quantitative documentation of significant disturbances in neurophysiological
      processes subserved by prefrontal cortex and the cerebellar vermis during
      episodes of major depression.

PMID- 9564442
TI  - Signal transduction by platelet adenylate cyclase: alterations in depressed
      patients may reflect impairment in the coordinated integration of cellular
      signals (coincidence detection).
AB  - BACKGROUND: Adenylate cyclase (AC) responds to distinct but coincident signals
      from the agonist-stimulated G-protein Gs and the inhibitory G-protein Gi by
      generating a greater output signal-to-noise ratio--i.e., agonist-stimulated to
      basal ratio (fold-stimulation)--through coincidence detection than that generated
      by a single input (Gs) alone. Such coincidence detection by murine brain AC was
      found to be enhanced during chronic antidepressant treatment with imipramine.
      METHODS: We examined and compared the basal, agonist-stimulated, and guanosine 5'
      3-O-(thio)triphosphate (GTP gamma S) or AlF4 ion postreceptor-stimulated AC
      activities in mononuclear leukocytes and platelets from the same blood specimens
      obtained from depressed patients (n = 27) and control subjects (n = 19). RESULTS:
      In all subjects, the differences (delta GTP gamma S or delta AlF4) between
      postreceptor measures of AC in mononuclear leukocytes (where AC is regulated by
      Gs but not by Gi) and platelets (where AC is regulated by both Gs and Gi) were
      highly significant. In controls, the relationships between delta GTP gamma S or
      delta AlF4 and basal, agonist-stimulated, and the fold-stimulation of agonist
      stimulated platelet AC resembled the regulation of AC by Gi in model-membrane
      systems. Comparable relationships between delta GTP gamma S or delta AlF4 and
      basal, agonist-stimulated, and the fold-stimulation of agonist-stimulated
      platelet AC activities were not observed in depressed patients. CONCLUSIONS: Our
      results suggest that in controls, platelet AC enzyme activity is determined (in
      part) by the coordinated integration of signals from Gs and Gi through
      coincidence detection, while such coincidence detection by platelet AC may be
      impaired in patients with depressive disorders.

PMID- 9564444
TI  - The effects of electroconvulsive shock on the primary cortical auditory
      potential.
AB  - BACKGROUND: Recording of evoked potentials provides an ideal method of
      quantifying the acute changes in neurophysiological activity that occur following
      the administration of electroconvulsive shock (ECS) or electroconvulsive therapy.
      METHODS: Serial recordings of the primary cortical auditory evoked potential
      (PCAEP) were made from 20 adult male albino rats starting immediately after the
      induction of generalized seizure activity by ECS. RESULTS: Directly after ECS,
      the PCAEP was abolished; however, an auditory potential that superficially
      resembled an abnormal PCAEP was invariably present during this period. On
      analysis, it was shown that this response was of probable thalamic origin, which
      had become unmasked due to the temporary absence of the normally dominant
      cortical potential. Within 1 min, the genuine PCAEP had begun to reappear, and
      its normal morphology was then rapidly restored. CONCLUSIONS: It was concluded
      that the principal site of action of ECS on the PCAEP may lie quite discretely
      within the cortex, while auditory activity generated in brain stem and
      subcortical locations is largely immune to its effects. It is suggested that the
      loss of the cortical waveform following ECS may be due to epileptogenic events
      responsible for the development of the paroxysmal depolarization shift, which
      temporarily block the formation of the postsynaptic PCAEP. The relevance of these
      findings for an understanding of the therapeutic efficacy of electroconvulsive
      therapy is discussed.

PMID- 9564445
TI  - Increased REM sleep density at admission predicts relapse by three months in
      primary alcoholics with a lifetime diagnosis of secondary depression.
AB  - BACKGROUND: Having previously reported that 3-month relapse was associated with
      increased admission REM pressure in nondepressed primary alcoholics, we
      hypothesized that baseline polysomnography would predict outcome in primary
      alcoholics with a lifetime diagnosis of secondary depression. METHODS: Twenty-one
      primary alcoholics with secondary depression received polysomnography and the
      Hamilton Depression Rating Scale during the first and fourth weeks of a 1-month
      inpatient alcohol treatment program. Exclusion criteria included serious illness,
      current major alcohol withdrawal symptoms, other Axis I diagnoses, sleep apnea,
      nocturnal myoclonus, and psychoactive substances within 14 days of
      polysomnography. Relapse was defined as drinking any alcohol between hospital
      discharge and 3-month follow-up. RESULTS: Relapsers' total sleep time was
      reduced, and REM density (reflecting REM sleep ocular activity) was increased
      significantly throughout admission compared with abstainers. Sleep continuity and
      Hamilton scores improved by discharge in sober and relapsing alcoholics. Factors
      derived from admission REM latency, REM percent, and REM density predicted
      sobriety vs. relapse within 3 months after hospital discharge in 76% of patients.
      Admission REM density was greater, and total sleep time was less in relapsers
      than in patients sober at 3 months. CONCLUSIONS: Results suggest that increased
      REM density and decreased total sleep time at about 2-4 weeks of abstinence
      predict relapse by 3 months in depressed alcoholics.

PMID- 9564446
TI  - Variation of ictal electroencephalographic regularity with low-, moderate-, and
      high-dose stimuli during right unilateral electroconvulsive therapy.
AB  - BACKGROUND: Previous work has demonstrated changes in electroencephalographic
      (EEG) ictal morphology during electroconvulsive therapy (ECT) as stimulus
      intensity is increased from barely suprathreshold to moderately suprathreshold.
      Our study reports on the reactivity of seizure regularity ratings in 11 subjects
      receiving right unilateral (RUL) ECT as the stimulus is varied over a wider range
      of intensities from low to medium, then high dose. METHODS: The stimulus
      intensity of all 11 subjects was first increased from barely suprathreshold to
      moderately suprathreshold, and then randomized to either stay at a moderately
      suprathreshold dose or increase to a high dose. The regularity of the EEG ictal
      discharge was visually measured on a seven-point scale. RESULTS: We found that
      seizure regularity increases as the stimulus intensity moves from the barely
      suprathreshold to the moderately suprathreshold dosage, but did not increase
      further when the stimulus increased to a high dose. CONCLUSIONS: These results
      suggest that EEG regularity is unlikely to distinguish moderately suprathreshold
      from markedly suprathreshold stimuli during RUL ECT.

PMID- 9564447
TI  - Antipanic effect of fluoxetine measured by CO2 challenge test.
AB  - BACKGROUND: Respiratory symptoms are important in panic disorder for frequency
      and intensity. Patients with this disorder are often chronic hyperventilators,
      and inhalation of carbon dioxide is a strong panicogenic stimulus. We tested the
      hypothesis of whether respiratory parameters may be used as indicators of the
      course of panic disorder during its treatment with fluoxetine. METHODS: Nine
      patients with panic disorders, previously shown to panic in response to
      intravenously administered lactate, and 10 control subjects underwent the Read
      rebreathing test by a 5-min inhalation of a 7% CO2/93% O2 mixture before and
      after 1 month of fluoxetine treatment. RESULTS: At baseline, patients differed
      from controls for higher percent value of expiratory reserve volume/vital
      capacity ratio and ventilatory response. Eight of the 9 patients had panic in
      response to the CO2 challenge. After fluoxetine, respiratory parameters decreased
      significatively, and only 3 patients remained hypercarbic challenge responders.
      CONCLUSIONS: The carbon dioxide challenge may represent a useful tool to evaluate
      the individual respiratory set, which may be a marker of the vulnerability to
      panic attack. Assessment of respiratory parameters may represent a biological
      marker to measure the efficacy of antipanic treatment.

PMID- 9564448
TI  - Density of imidazoline receptors in platelets of euthymic patients with bipolar
      affective disorder and in brains of lithium-treated rats.
AB  - BACKGROUND: Platelet imidazoline receptors have been shown to be up-regulated in
      patients with unipolar major depression. This study examines the status of
      imidazoline receptor proteins in platelets of euthymic bipolar patients and in
      brains of lithium-treated rats. METHODS: Platelets were collected from 12 bipolar
      patients (lithium-treated or drug-free) and brains from chronic lithium-treated
      rats. Imidazoline receptors were quantitated by immunoblotting, using a specific
      antiserum, and/or radioligand binding. RESULTS: No changes in platelet
      imidazoline receptors (35-kDa and 45-kDa proteins) were found. Lithium treatment
      did not alter brain imidazoline receptors (29/30-kDa, 45-kDa, and 66-kDa proteins
      or density/affinity of [3H]-idazoxan binding sites). CONCLUSIONS: Imidazoline
      receptor proteins are not altered in platelets of euthymic patients with bipolar
      affective disorder.

PMID- 9564449
TI  - Cerebrospinal fluid monoamine metabolites and glucose metabolism in posttraumatic
      aggression.
AB  - BACKGROUND: This pilot study was conducted to determine if aggressive, post brain
      injured patients have abnormal glucose metabolism or abnormal CSF monoamine
      metabolite concentrations as compared with non-aggressive, post brain-injured
      controls. METHODS: Subjects with a history of traumatic brain injury underwent a
      lumbar puncture and glucose tolerance test after a three-week medication wash-out
      period. Monoamine metabolite concentrations and glucose nadirs were compared
      between aggressive and control subjects. RESULTS: There were no statistical
      differences between the aggressive (n = 4) and control (n = 6) group with respect
      to age (28.5 +/- 15.7 versus 28.0 +/- 10.8), weight (72.5 kg +/- 14.1 versus 67.7
      kg +/- 10.1) or number of months since brain injury (31.8 +/- 26.1 versus 33.3 +/
      23.3). There were no significant differences between the two groups in glucose
      nadirs following oral glucose challenge or in levels of CSF monoamine metabolite
      concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA),
      or 3-methoxy-4-hydroxyphenylglycol (MHPG), although a trend toward significance
      was noted between the MHPG groups (higher MHPG within aggressive group).
      CONCLUSIONS: The preliminary data suggest that glucose metabolism and CSF
      monoamine metabolite concentrations do not differ significantly from aggressive
      subjects to controls in persons with brain injury. Follow-up prospective studies
      with larger sample sizes are needed to evaluate these preliminary findings.

PMID- 9564450
TI  - Working memory constraints on syntactic ambiguity resolution as revealed by
      electrical brain responses.
AB  - Parsing strategies in temporarily ambiguous sentences were investigated in
      readers with different sentence memory capacities using event-related brain
      potentials (ERPs). Readers with a high memory span as well as readers with a low
      memory span were required to read subject and object relative sentences which
      were either ambiguous until the last word (late disambiguation) or were
      disambiguated by case marking either the clause initial pronoun (immediate
      disambiguation) or the noun phrase following it (early disambiguation). ERPs
      registered during sentence reading elicited the following effects: In the late
      disambiguation condition, high span readers, but not low span readers, displayed
      a more positive going wave at the disambiguating number marked auxiliary for the
      object relative sentences than for the subject relative sentences. This
      positivity is taken to reflect processes of revision that become necessary at the
      disambiguating element if the initial structure considered is a subject relative
      clause. When case marking was available in the clause initial at the relative
      pronoun, both high and low span readers showed a positivity at the disambiguating
      element for the object relative sentences, suggesting the immediate use of case
      marking information for revision. When case marking was available in the noun
      phrase following an ambiguous pronoun both groups showed no clear effect of
      revision at the disambiguating element, but only at the sentence final number
      marked auxiliary. This non-immediate use of the case marking information seems to
      be due to an inherent ambiguity in the German case marking system which interacts
      with the disambiguating element's position in the sentence. The combined data
      indicate that morphological information can be used immediately by high and low
      span readers to resolve syntactic ambiguity during sentence processing whenever
      the information given is clearly unambiguous. In addition they suggest that
      possible processing differences in ambiguity resolution between high and low span
      readers may only appear when the ambiguous regions are long.

PMID- 9564451
TI  - Changes in heart beat timing: reactivity, resetting, or perturbation?
AB  - A widely held hypothesis within behavioral medicine is that cardiovascular
      reactivity is a risk factor for cardiovascular disease. The measurement model for
      this cardiovascular reactivity is rather simple. A basal level of function is
      seen to increase while the organism is stressed and then return to basal
      function. We argue that this model is incomplete and that other forms of
      'reactivity' may be relevant to pathophysiology. A pathophysiological hypothesis
      is discussed which assumes a cyclic heart beat generation mechanism that is
      sensitive to stimulation only at certain phases of its cycle. Implications of
      this hypothesis for measurement are developed to illustrate the point that models
      of normal function can determine the measures most relevant to pathophysiology.

PMID- 9564452
TI  - Anxiety and autonomic flexibility: a cardiovascular approach.
AB  - Autonomic characteristics of panickers, blood phobics, and nonanxious controls
      were compared with a variety of cardiovascular measures, including spectral
      analysis of the cardiac inter-beat interval time series (derived from the
      electrocardiogram). Responses to laboratory stressors (shock avoidance and cold
      face stress) of 16 participants who reported recent occurrences of frequent
      severe panic attacks, 15 participants who reported strong somatic reactions and
      fainting to the sight of blood, and 15 controls, were recorded. Results suggested
      distinct autonomic patterns among the three groups. Across conditions, panickers
      displayed the highest heart rates (HR) coupled with the least HR variability,
      which indicates low levels of cardiac vagal tone. Blood phobics showed more
      vagally mediated HR variability than panickers, with a significant association
      between cardiac rate and mean arterial pressure. Controls generally showed the
      most HR variability and 'spectral reserve' (a quality that indicates flexible
      responsivity). Results are discussed in the context of traditional models of
      anxiety and autonomic activity in contrast to contemporary notions of stability
      and change in biological systems.

PMID- 9564453
TI  - The effect of autonomic nervous system activity on gastric myoelectrical
      activity: does the spectral reserve hypothesis hold for the stomach?
AB  - Previous studies have associated changes in gastric myoelectrical activity during
      motion sickness, as indexed using the electrogastrogram (EGG), with changes in
      autonomic nervous system (ANS) activity. Subjects who did not report nausea in a
      rotating optokinetic drum were characterized by normal 3 cycles per minute (cpm)
      gastric myoelectrical activity, strong parasympathetic nervous system (PNS)
      activity, and low sympathetic nervous system (SNS) activity. The goals of this
      study were: (1) to determine whether tasks previously shown to alter ANS activity
      as indexed by changes in cardiac inter-beat intervals (IBIs) would result in
      systematic changes in gastric myoelectrical activity in accord with the findings
      from motion sickness studies; and (2) to determine whether the 'spectral reserve
      hypothesis' applies to gastric myoelectrical activity. EGGs and IBIs were
      collected from 24 healthy subjects during resting/baseline, reaction time/shock
      avoidance (RT) and cold face stress (CF) tasks. Tachyarrhythmia was found to be
      significantly greater during the RT task than during the baseline and CF tasks.
      It was concluded that: (1) tasks that alter ANS activity do systematically alter
      gastric myoelectrical activity; and (2) gastric myoelectrical activity does not
      follow the cardiac model of health being associated with increased spectral
      complexity.

PMID- 9564454
TI  - Serum lipids and cardiovascular reactivity to stress.
AB  - Several studies have reported an association between serum lipid levels and
      cardiovascular reactivity to laboratory stressors. Their findings, however, are
      equivocal. The inconsistencies may be due to shortcomings such as the small
      number of subjects, the inclusion of patient groups, no control for medication,
      and no control for age effects. Two studies are presented investigating the
      relationship in large groups of adolescent and middle-aged males and females.
      Cholesterol, triglycerides and HDL were measured. Subjects were exposed to mental
      stressors, and in one study also to a cold pressor test. In addition to heart
      rate and blood pressure, in one study impedance cardiography was used to measure
      pre-ejection period, stroke volume and total peripheral resistance. Canonical
      correlation analysis suggested an association between triglycerides and decreased
      cardiac reactivity to mental stressors in middle-aged females. Trends in the same
      direction were found in both middle-aged males and females with respect to
      reactivity to the cold pressor. These associations, however, were not confirmed
      when the extreme deciles of the triglyceride distributions were compared with
      respect to stress reactivity. The fact that associations were completely absent
      in youngsters but sometimes showed up in older persons suggested an age
      dependency of the association. In post hoc analyses, indeed, some evidence was
      found for stronger cardiac responsivity being associated with cholesterol
      specifically in relatively older males. In females, in contrast to this, the
      association between triglycerides and cardiac responsivity was stronger in the
      younger group. More detailed measurement techniques, of specifically vascular
      processes, may be needed to explore further the effects of sex and age on the
      association between lipids and stress reactivity.

PMID- 9564455
TI  - Invasive aspergillosis.

PMID- 9564456
TI  - Effect of prophylaxis on the clinical manifestations of AIDS-related
      opportunistic infections.
AB  - Administration of targeted prophylaxis for AIDS-related opportunistic infections
      has contributed significantly to the recent decrease in mortality among patients
      with AIDS in the United States. Most reported prophylaxis trials have focused on
      determining (a) the percentage of cases prevented and (b) the effect of
      widespread antibiotic use on drug susceptibility. A third phenomenon that is
      seldom reported on is the attenuating effect of failed prophylaxis on the
      clinical presentation of opportunistic infections (OIs). With the increasingly
      widespread use of prophylaxis for OIs, more atypical "breakthrough" cases of
      opportunistic infections will be seen. Reports of clinical changes are reviewed
      below. Investigators should routinely report the clinical manifestations of
      breakthrough cases in all articles pertaining to prophylaxis for opportunistic
      infections in patients with AIDS.

PMID- 9564457
TI  - Community-acquired pneumonia in adults: guidelines for management. The Infectious
      Diseases Society of America.
AB  - This is part of the series of practice guidelines commissioned by the Infectious
      Diseases Society of America through its Practice Guidelines Committee. The
      purpose of this guideline is to provide assistance to clinicians in the diagnosis
      and treatment of community-acquired pneumonia. The targeted providers are
      internists and family practitioners. The targeted groups are immunocompetent
      adult patients. Criteria are specified for determining whether the inpatient or
      outpatient setting is appropriate for treatment. Differences from other
      guidelines written on this topic include use of laboratory criteria for diagnosis
      and approach to antimicrobial therapy. Panel members and consultants are experts
      in adult infectious diseases. The guidelines are evidence based where possible. A
      standard ranking system is used for the strength of the recommendations and the
      quality of the evidence cited in the literature reviewed. The document has been
      subjected to external review by peer reviewers as well as by the Practice
      Guidelines Committee and was approved by the IDSA Council. An executive summary
      and tables highlight the major recommendations. The guidelines will be listed on
      the IDSA home page at http://www.idsociety.org.

PMID- 9564458
TI  - Photo quiz I. Varicella zoster virus-associated leukocytoclastic vasculitis.

PMID- 9564459
TI  - Association between interleukin-8 concentration in nasal secretions and severity
      of symptoms of experimental rhinovirus colds.
AB  - The purpose of this study was to examine the association between experimental
      rhinovirus infection and the elaboration of interleukin-8 (IL-8) into nasal
      secretions of volunteers and to determine the effect of pentoxifylline on IL-8
      elaboration and rhinovirus-associated common cold symptoms. Fifty-four subjects
      with experimental rhinovirus infections and 20 sham-inoculated subjects were
      studied. Pentoxifylline had no effect on rhinovirus-induced symptoms or nasal
      secretion IL-8 concentrations. IL-8 concentrations were significantly greater in
      nasal secretions from infected symptomatic subjects than in those from infected
      asymptomatic or sham-challenged subjects on days 2-4 after virus challenge. In
      infected subjects, there was significant rank correlation between nasal
      obstruction severity, rhinorrhea severity, and nasal-wash albumin concentrations
      and the change in IL-8 concentration from baseline on days 2-4 after virus
      challenge.

PMID- 9564460
TI  - The host response, not the virus, causes the symptoms of the common cold.

PMID- 9564461
TI  - Photo quiz II. Leukocytoclastic vasculitis secondary to parvovirus B19 infection.

PMID- 9564462
TI  - Hyperparasitemia and blood exchange transfusion for treatment of children with
      falciparum malaria.
AB  - A substantial number of reports of cases and small investigations support blood
      exchange transfusion as a therapy for hyperparasitemia in cases of Plasmodium
      falciparum malaria, although a prospective and randomized study has never been
      undertaken. We report on 113 prospectively enrolled children in Lambarene, Gabon,
      who had more than 10% parasitized erythrocytes and were treated with chemotherapy
      alone. All 86 patients with hyperparasitemia as the sole complication recovered
      uneventfully. Among the 27 patients who had additional complications, parasitemia
      levels as high as 81% responded well to chemotherapy alone. Two patients with
      cerebral malaria, who also had other complications and hence a poor prognosis,
      died. Hyperparasitemia itself might be important for the development of a fatal
      event in malaria, but a recommendation to perform a dangerous, expensive, and
      labor-intensive procedure such as blood exchange transfusion for its treatment
      should be based on substantial clinical research, especially in areas where
      malaria is a major health problem.

PMID- 9564463
TI  - Exchange blood transfusion in severe falciparum malaria--the debate goes on.

PMID- 9564464
TI  - Behavioral and demographic risk factors for transmission of human
      immunodeficiency virus type 1 in heterosexual couples: report from the
      Heterosexual HIV Transmission Study.
AB  - We compared 224 heterosexual couples who were discordant for human
      immunodeficiency virus (HIV) type 1 infection (one partner HIV infected) with 78
      HIV-concordant couples (both partners HIV infected) to identify demographic and
      behavioral risk factors for HIV transmission. Among the 229 couples whose male
      partner was first infected, HIV-concordant couples had engaged in anal sex more
      frequently before and after knowing that the male was infected than had HIV
      discordant couples. Pap smears of grade 2 or higher (inflammation) were more
      prevalent among the second-infected female partners in HIV-concordant couples
      than among uninfected women in discordant couples (58% vs. 23%; P < .001). Anal
      sex and unprotected vaginal sex after knowledge of a male partner's infection
      were significant correlates of concordance in a multivariate logistic model, as
      were ethnicity, marital status, and antiviral therapy. Ethnicity strongly
      predicted concordance, even after controlling for sexual risk behaviors and stage
      of disease.

PMID- 9564465
TI  - Cytomegalovirus disease as a risk factor for graft loss and death after
      orthotopic liver transplantation.
AB  - To determine whether cytomegalovirus (CMV) disease is an independent risk factor
      for graft loss and death after orthotopic liver transplantation, we performed a 3
      year follow-up study of 143 consecutive liver transplant recipients and six
      patients who underwent retransplantation. Thirty-seven patients (25%) had had CMV
      disease and were alive after treatment. Fifty-two deaths and eight graft losses
      occurred. The cumulative incidence of graft failure at 1 and 3 years of follow-up
      were 40% and 63%, respectively, for patients with CMV disease, compared with 22%
      and 33%, respectively, for those without CMV disease (P < .05, logrank test).
      Cumulative probabilities of survival for patients with and without CMV disease
      were 64% and 82%, respectively, at 1 year and 46% and 69%, respectively, after 3
      years (P < .05, logrank test). Multivariate analysis with use of a time-dependent
      Cox model showed that previous CMV disease was an independent risk factor for
      graft loss at 1 and 3 years of follow-up (P = .04 and P = .007) and for patient
      survival (P = .04 and P = .01). Our results indicate that CMV disease is a
      significant independent risk factor for graft loss and patient survival after
      liver transplantation.

PMID- 9564466
TI  - Cytomegalovirus disease and allograft loss after organ transplantation.

PMID- 9564468
TI  - Beta-lactam drugs and tuberculosis.

PMID- 9564467
TI  - Activity of amoxicillin/clavulanate in patients with tuberculosis.
AB  - Some beta-lactam antibiotics are active in vitro against Mycobacterium
      tuberculosis. There are anecdotal reports of successful treatment of tuberculosis
      caused by multiple-drug-resistant strains of M. tuberculosis with regimens that
      included amoxicillin/clavulanate. Reduction of M. tuberculosis in the sputum of
      patients with pulmonary tuberculosis during administration of
      amoxicillin/clavulanate was measured by a quantitative culture method to
      determine the activity in vivo. Patients were randomized to receive isoniazid,
      ofloxacin, or amoxicillin/clavulanate for 7 days. Isoniazid was the most
      effective agent, reducing M. tuberculosis after 2 days at a mean rate (+/-
      standard deviation) of 0.60 +/- 0.30 log10 cfu/mL per day, compared with 0.32 +/-
      0.05 and 0.34 +/- 0.03 for ofloxacin and amoxicillin/clavulanate, respectively.
      The early bactericidal activity of amoxicillin/clavulanate was comparable to that
      reported for antituberculous agents other than isoniazid. Further studies of beta
      lactam antibiotics with in vitro activity against M. tuberculosis are warranted
      to define their role in treatment of tuberculosis.

PMID- 9564469
TI  - Impact of epidemic influenza A-like acute respiratory illness in a remote jungle
      highland population in Irian Jaya, Indonesia.
AB  - A suspected epidemic of unknown etiology was investigated in April/May 1996 in
      the remote jungle highlands of easternmost Indonesia. Trend analysis demonstrates
      the area-wide occurrence of a major respiratory infection outbreak in November
      1995 through February 1996. The monthly mean rate of respiratory infection
      episodes for the peak outbreak months (2,477 episodes/100,000 persons) was
      significantly higher (P < .0001) than for the 34 months leading up to the
      outbreak (109 episodes/100,000 persons). Notable were the high attack rates,
      particularly among adults: 202 episodes/1,000 persons aged 20-50 years in one
      community. Excess morbidity attributed to the outbreak was an estimated 4,338
      episodes. The overall case-fatality rate was 15.1% of outbreak cases. Laboratory
      evidence confirmed the circulation of influenza A/Taiwan/1/86-like viruses in the
      study population, and high hemagglutination inhibition titer responses were
      indicative of recent infections. Historical documents from neighboring Papua New
      Guinea highlight the role of influenza A virus in repeated area outbreaks.

PMID- 9564470
TI  - Burkholderia pseudomallei infection in a Puerto Rican patient with chronic
      granulomatous disease: case report and review of occurrences in the Americas.
AB  - Burkholderia species, notably Burkholderia cepacia and Burkholderia gladioli, are
      important pathogens in patients with chronic granulomatous disease (CGD).
      Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in
      Southeast Asia and northern Australia but is a rare pathogen in other parts of
      the world. We describe the occurrence of B. pseudomallei infection in a Puerto
      Rican patient with CGD. This is one of only a small number of documented cases of
      melioidosis autochthonous to the Americas and is the first reported case of B.
      pseudomallei infection in a CGD patient from the Americas. We conclude that B.
      pseudomallei, like B. cepacia and B. gladioli, should be considered a potential
      pathogen in patients with CGD and that melioidosis should be considered in the
      differential diagnosis for ill residents of or travelers to Puerto Rico.

PMID- 9564471
TI  - Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core
      antigen who subsequently received hepatitis B vaccine.
AB  - Serum samples from 133 persons who were positive only for antibody to hepatitis B
      core antigen (anti-HBc) by enzyme immunoassay (EIA) were retested for seromarkers
      of hepatitis B virus (HBV) by radioimmunoassay and for HBV DNA by polymerase
      chain reaction analysis. All persons were subsequently vaccinated with hepatitis
      B vaccine. HBV DNA was found in only five persons, four of whom remained positive
      during retesting. Most persons had a primary antibody response with three doses
      of hepatitis B vaccine. Evidence of HBV DNA was not detected in 96% of persons
      with isolated anti-HBc by EIA.

PMID- 9564472
TI  - Clinical features of infections due to Escherichia coli producing heat-stable
      toxin during an outbreak in Wisconsin: a rarely suspected cause of diarrhea in
      the United States.
AB  - In September 1994, a foodborne outbreak of enterotoxigenic Escherichia coli
      (ETEC) infection occurred in attendees of a banquet in Milwaukee. E. coli was
      isolated from stool specimens from 13 patients that were comprehensively tested;
      isolates from five patients were positive for E. coli producing heat-stable
      toxin, were biochemically identified and serotyped as E. coli O153:H45, and were
      all resistant to tetracycline, ampicillin, sulfisoxazole, and streptomycin.
      Diarrhea (100%) and abdominal cramps (83%) were the most prevalent symptoms in
      205 cases; vomiting (13%) and fever (19%) were less common. The median duration
      of diarrhea and abdominal cramps was 6 days and 5 days, respectively. In the
      United States, health care providers rarely consider ETEC as a possible cause of
      diarrhea in their patients, and few laboratories offer testing to identify ETEC.
      Hence, outbreaks of ETEC infection may be underdiagnosed and underreported. As in
      this outbreak, the relatively high prevalence of diarrhea and cramps lasting > or
      = 4 days and the low prevalence of vomiting and fever can help distinguish ETEC
      infection from Norwalk-like virus infection and gastroenteritis due to other
      causes with incubation times of > or = 15 hours and can provide direction for
      confirmatory laboratory testing.

PMID- 9564473
TI  - Correlation of in vitro fluconazole susceptibility with clinical outcome for
      severely ill patients with oropharyngeal candidiasis.
AB  - We investigated the correlation between in vitro susceptibility to fluconazole
      and clinical response in severely ill patients with oropharyngeal candidiasis
      treated with fluconazole. The study included 48 adult patients, of whom 23 were
      neutropenic (absolute neutrophil count, < 500/mm3). Forty-eight isolates (20
      Candida albicans, 12 Candida krusei, 10 Candida kefyr, 3 Torulopsis glabrata, and
      3 Candida tropicalis) were tested for susceptibility to fluconazole with use of
      the macrodilution method of the National Committee for Clinical Laboratory
      Standards. A strain was considered to be susceptible to fluconazole if the MIC
      was < or = 8 micrograms/mL and resistant if the value was > or = 64
      micrograms/mL. All but one of the resistant strains were C. krusei isolates.
      Species of causative Candida, persistent neutropenia, and susceptibility to
      fluconazole were significant predictors of clinical response by univariate
      analysis. Logistic regression analysis indicated that the only significant factor
      was the species of Candida isolates, validating the recently recommended MIC
      breakpoint and the correlation between clinical outcome and in vitro antifungal
      susceptibility.

PMID- 9564474
TI  - Transverse myelitis associated with Mycoplasma pneumoniae infection.
AB  - A 14-year-old boy developed acute transverse myelitis with severe abdominal pain,
      bladder dysfunction, weakness, and sensory loss of the lower extremities.
      Magnetic resonance imaging revealed a segmental expanded central edema affecting
      parts of the spinal cord, including the caudal medulla oblongata. Antibody
      response to Mycoplasma pneumoniae was negative in microparticle agglutination
      assays (1:40 in the acute serum and 1:160 in the convalescent serum) and
      complement fixation tests (1:20 and 1:10). However, analysis of acute-phase serum
      revealed a specific IgA and IgG response but no IgM response. Detection of M.
      pneumoniae in the cerebrospinal fluid by nested polymerase chain reaction and in
      nasopharyngeal aspirate by culture confirmed an M. pneumoniae infection.
      Treatment with doxycycline (100 mg daily) was started on the second day after
      admission to the hospital and continued for 14 days; the patient recovered
      completely and was discharged 20 days after onset of the disease, with no signs
      of neurological deficits.

PMID- 9564475
TI  - Influenza vaccine efficacy in young, healthy adults.
AB  - Findings concerning influenza vaccine efficacy in young, healthy adults are
      inconsistent. A high incidence of influenza in the winter of 1995 provided an
      opportunity to study the efficacy of influenza vaccine among young, healthy
      military personnel. Influenza activity was confirmed by isolation of influenza A
      and B viruses from nasopharyngeal swab specimens from hospitalized soldiers. Self
      administered questionnaires concerning vaccination status and disease symptoms
      were used in two study groups: recruits and veteran soldiers serving in different
      camps. Six hundred eighty-four individuals had received influenza vaccine and 652
      had not. Vaccine efficacy was found to be 38.1% (P = .002) for preventing febrile
      illness with or without symptoms and slightly higher (41.6%; P < .001) for
      preventing fever together with upper respiratory tract symptoms. The current
      influenza vaccine significantly reduced febrile illness among healthy military
      personnel.

PMID- 9564476
TI  - Plasma patterns of tumor necrosis factor-alpha (TNF) and TNF soluble receptors
      during acute meningococcal infections and the effect of plasma exchange.
AB  - In 39 patients with acute meningococcal infections, the plasma concentrations of
      tumor necrosis factor-alpha (TNF) and its soluble receptors (sRs) TNFsR-p55 and
      TNFsR-p75 were measured from admission till recovery. At admission, patients with
      shock had significantly higher TNF, TNFsR-p55, and TNFsR-p75 values than patients
      without shock. In addition, during the first 24 hours, patients with shock had
      higher TNFsR-p75 to TNFsR-p55 ratios, indicating that in shock the increase of
      TNFsR-p75 exceeds that of TNFsR-p55. TNF measured more than 12 hours after
      admission failed to differentiate between shock and nonshock because TNF
      concentrations normalized within 12-24 hours. However, because concentrations of
      TNFsRs remained elevated for 5-6 days, at that time plasma TNFsRs still
      differentiated between shock and nonshock. Plasma exchange or whole blood
      exchange (PEBE), performed in 20 patients with shock, accelerated the decrease of
      plasma TNFsRs. However, because of a rebound after each PEBE session, the overall
      half-lives of both TNFsRs were not affected by PEBE.

PMID- 9564477
TI  - Psychiatric diseases presenting as infectious diseases.
AB  - Although many psychiatric diseases have somatic manifestations, some focus on
      fears or delusions of infection. When a patient with a psychiatric basis for an
      apparent infection presents to an infectious disease physician, the physician may
      find the problem confusing, amusing, and ultimately frustrating until the
      psychiatric basis for disease is recognized. Some of these psychiatric disorders
      can be treated and controlled with medication and psychotherapy, although
      patients may resist psychiatric referral. This article reviews examples of
      psychiatric disorders in patients who present to the infectious disease
      physician, including factitious infection, malingering, obsessive compulsive
      disorder, phobias, veneroneuroses, somatization disorders, and delusional
      infection. The role that physicians play in amplifying these disorders is
      reviewed. Strategies for referral to psychiatric services are also discussed.
      Patients with a psychiatric disease are seen in infectious disease practices more
      commonly than physicians realize.

PMID- 9564478
TI  - Increases in levels of antibody to hepatitis B surface antigen in an immunized
      population.
AB  - Hepatitis B vaccine is effective in preventing infection with hepatitis B virus
      (HBV), but its duration of protection is unknown. To examine the effect of
      exposure to HBV on an immunized population, data were analyzed from a cohort of
      Alaska Natives who were immunized and then followed up annually for 10 years. A
      boost in antibody to hepatitis B surface antigen (anti-HBs) was defined as a
      fourfold rise in levels to > or = 20 mIU/mL that was not accompanied by the
      presence of antibody to hepatitis B core antigen or attributable to interim
      vaccination. During 10 years of follow-up, 8.2% of 1,595 vaccines had boosts in
      anti-HBs. Persons with boosts did not differ significantly from those without
      boosts in terms of age, gender, village, initial level of anti-HBs, or level of
      anti-HBs before the boost. These results underscore the continued exposure to HBV
      among vaccinees and the continued protection against disease that the vaccine
      provides.

PMID- 9564479
TI  - Aerobic and anaerobic microbiology of retroperitoneal abscesses.
AB  - The aerobic and anaerobic microbiology of various types of retroperitoneal
      abscesses was studied by review of the clinical and laboratory data for 161
      patients treated between 1974 and 1990 for such abscesses. These included 109
      anterior, 8 posterior, 21 retrofascial, and 23 pelvic retroperitoneal abscesses.
      A total of 472 organisms (2.9 isolates/specimen)--204 aerobic and facultative
      (1.3/specimen), and 268 anaerobic (1.7/specimen)--were recovered. Aerobes only
      were recovered from 34 abscesses (21%), anaerobes only from 34 (21%), and mixed
      aerobic and anaerobic bacteria from 93 (58%). Polymicrobial infection was present
      in 132 patients (82%). The predominant aerobic and facultative isolates were
      Escherichia coli (60 isolates), Klebsiella pneumoniae (20), Streptococcus group D
      (19), and Staphylococcus aureus (11). The predominant anaerobes were
      Peptostreptococcus species (95 isolates), Bacteroides fragilis group (66),
      Prevotella species (22), and Clostridium species (22). The number of anaerobes
      per site always was greater than the number of aerobic or facultative organisms
      and was especially high in pelvic abscesses. The number of aerobic and
      facultative organisms was especially high in pancreatic abscesses. These data
      highlight the polymicrobial aerobic-anaerobic nature of retroperitoneal
      abscesses.

PMID- 9564480
TI  - Candidal epididymo-orchitis: case report and review.
AB  - We describe a case of epididymo-orchitis with candiduria and histologically
      proven epididymal abscesses due to Candida albicans and review six previously
      reported cases. Candidal epididymo-orchitis occurs in patients with recognized
      risk factors for candidal infection, often after instrumentation of the urinary
      tract. Cases caused by both C. albicans and Candida glabatra have been described.
      Drainage or orchidectomy may be required for definitive diagnosis and treatment.
      Treatment with oral antifungals alone has been effective in two cases.

PMID- 9564481
TI  - Efficacy of oral pyronaridine for the treatment of acute uncomplicated falciparum
      malaria in African children.
AB  - Pyronaridine is a new antimalarial agent developed in China. In this randomized,
      unblinded study, the safety, tolerance, and clinical efficacy of pyronaridine (n
      = 44) were evaluated and compared with those of chloroquine (n = 44), the
      standard first-line antimalarial drug in most of Africa, in 88 Cameroonian
      children with acute uncomplicated falciparum malaria. The target sample size was
      determined to detect a 35% difference in in vivo resistance between the two
      treatment groups, with 95% power. Clinical and parasitological responses were
      monitored for 14 days on an outpatient basis. Seven children (3 treated with
      pyronaridine and 4 treated with chloroquine) were lost to follow-up and were
      excluded from the analysis. All 41 patients treated with pyronaridine were cured.
      Treatment failure was observed in 16 (40%) of the 40 children treated with
      chloroquine. In vitro assays indicated that 23 of 40 clinical isolates obtained
      from patients treated with pyronaridine were resistant in vitro to chloroquine.
      Side effects associated with pyronaridine intake were minor and transient.
      Pyronaridine is safe and well tolerated by symptomatic Cameroonian children, and
      it is highly efficacious in Africa, where chloroquine resistance is well
      established.

PMID- 9564482
TI  - Risk factors for early recurrent Clostridium difficile-associated diarrhea.
AB  - Recurrence is a common sequela of Clostridium difficile-associated diarrhea (CDD)
      and may increase morbidity, costs, and treatment-related antimicrobial
      resistance. Because recurrent CDD (RCDD) frequently occurs very soon after an
      initial episode, our goal was to determine the risk factors for early RCDD
      (occurring < or = 45 days after the initial episode). We conducted a case-control
      study, comparing 13 patients with early RCDD (case patients) with 46 patients who
      had only one CDD episode (control patients) at Centre Hospitalier Angrignon
      (Quebec) during January 1993 through November 1994. Risk factors for early RCDD
      included a history of chronic renal insufficiency, a white blood cell count of >
      or = 15 x 10(3)/mm3, and community-acquired diarrhea with the first CDD episode.
      For seven of eight case patients, C. difficile strains from the first and second
      CDD episodes were identical, suggesting that relapse is more common than
      reinfection. These results suggest that treatments should be directed at
      preventing relapses in patients at high risk for early RCDD.

PMID- 9564483
TI  - Clinical evaluation and microbiology of oropharyngeal infection due to
      fluconazole-resistant Candida in human immunodeficiency virus-infected patients.
AB  - Signs and symptoms of oropharyngeal candidiasis (OPC) were correlated with
      microbiology and clinical response to fluconazole in a cohort of patients with
      advanced human immunodeficiency virus (HIV) infection and recurrent OPC. Sixty
      four HIV-infected patients with a median CD4 cell count of < 50/mm3 (range, 3
      318/mm3) who presented with OPC were enrolled in a longitudinal study. Specimens
      for cultures were taken weekly until clinical resolution. Therapy with
      fluconazole was increased weekly as required to a maximum daily dose of 800 mg
      until resolution of symptoms and oral lesions. Resistant or dose-dependent
      susceptible yeasts, defined as a minimum inhibitory concentration of > or = 16
      micrograms/mL, were detected in 48 (31%) of 155 episodes. Clinical resolution
      with fluconazole therapy occurred in 107 (100%) of 107 episodes with susceptible
      yeasts vs. 44 (92%) of 48 episodes with resistant or dose-dependent susceptible
      strains (P = .008). Patients from whom fluconazole-resistant yeasts were isolated
      required longer courses of therapy and higher doses of fluconazole for response,
      but overall, excellent responses to fluconazole were seen in patients with
      advanced HIV infection.

PMID- 9564484
TI  - Pyogenic bacterial pneumonia in human immunodeficiency virus-infected inpatients:
      a clinical, radiological, microbiological, and epidemiological study.
AB  - We prospectively studied features of pyogenic bacterial pneumonia in 263
      consecutive human immunodeficiency virus-infected inpatients over a 6-month study
      period. Risk factors for bacterial pneumonia were examined by a case-control
      study that included 33 cases who presented with at least one episode of bacterial
      pneumonia and 80 controls without bacterial pneumonia. The estimated cumulative
      incidence of bacterial pneumonia per year was 12.5 cases per 100 inpatients (95%
      confidence interval [CI], 8.8-17.2). The 38 episodes of bacterial pneumonia that
      occurred in the 33 inpatients were mainly unilateral, but 32 episodes were patchy
      lobar or diffuse infiltrates. Microbiological etiologies were obtained in 33 of
      the 38 episodes of bacterial pneumonia. Thirty-seven pathogens were identified,
      including Streptococcus pneumoniae (16, of which 12 had a decreased
      susceptibility to penicillin), Haemophilus influenzae (6), and Pseudomonas
      aeruginosa (6). The risk factors for bacterial pneumonia that were identified
      after logistic regression included prior sinusitis within 1 month before
      admission (odds ratio [OR], 3.2; 95% CI, 1.1-9.1) and prior bacterial infection
      of the lower respiratory tract within 6 months before admission (OR, 3.1; 95% CI,
      1.1-8.3).

PMID- 9564485
TI  - Antimicrobial susceptibility testing: general principles and contemporary
      practices.

PMID- 9564486
TI  - Recurrent pneumococcal bacteremia: 34 episodes in 15 patients.
AB  - Thirty-four episodes of pneumococcal bacteremia were identified in 15 patients
      over 5 years in 10 hospitals in Franklin County, Ohio. Twelve patients each had 2
      episodes of pneumococcal bacteremia, 2 had 3, and 1 had 4. All patients had
      predisposing conditions, with lymphoma, multiple myeloma, and chronic obstructive
      pulmonary disease being the most frequent. The mean interval between the first
      and second episode was 268 days. Serotyping and genotyping were performed on 29
      isolates. The same serotypic and genotypic patterns were found for sequential
      isolates from four patients; three of these patients had a recurrence between 22
      and 90 days after a previous episode. Seven (24%) of the 29 isolates were
      serotype 23F; four isolates (14%) were not susceptible to penicillin. All of our
      patients received appropriate antimicrobial therapy and appeared to be clinically
      cured of their initial infection. For patients with recurrent pneumococcal
      disease, alternate preventive measures such as immunization with conjugate
      pneumococcal vaccine and/or prophylactic antibiotic therapy should be considered.

PMID- 9564487
TI  - Difficult-to-treat trichomoniasis: results with paromomycin cream.
AB  - Vaginal trichomoniasis poses a difficult therapeutic challenge when metronidazole
      is ineffective or contraindicated. We conducted a retrospective study of 6.25%
      paromomycin cream in the treatment of nine women referred with cases of vaginal
      trichomoniasis where metronidazole resistance or allergy was present. Results
      obtained immediately and 1 month after treatment were reviewed. The median age of
      the patients was 46 years; four women were nulliparous. The median symptom
      duration was 1 year. Five women were allergic to metronidazole. In four cases,
      resistance to high doses of metronidazole was demonstrated. Smears or cultures
      were positive immediately after treatment for three patients; a fourth relapsed 2
      weeks later. Of these patients for whom treatment failed, one was cured with a 3
      week course of paromomycin cream, and another was successfully treated with
      paromomycin cream and oral tinidazole. Three patients developed vaginal
      ulcerations that resolved spontaneously. Adverse effects may be a result of local
      formulation. Paromomycin cream was useful for treatment of cases of trichomonas
      infection where metronidazole resistance or allergy was encountered.

PMID- 9564488
TI  - Absidia corymbifera infections in neonates.
AB  - We report the first two documented cases of neonatal zygomycosis caused by
      Absidia corymbifera. A premature infant developed disseminated disease from a
      cutaneous site with pulmonary, gastrointestinal, and cerebral involvement. The
      infant died despite amphotericin B therapy and surgical debridement. The second
      case occurred in a full-term infant with congenital heart disease and fungal
      pneumonitis. Zygomycosis was not suspected because of underlying cardiac disease
      and a complicated postoperative course, and this infant also died. Absidia joins
      a growing list of opportunistic fungal pathogens of the compromised neonate.

PMID- 9564489
TI  - Gingivomandibular infection due to Mycobacterium kansasii in a patient with AIDS.

PMID- 9564490
TI  - Still's disease, severe thrombocytopenia, and acute hepatitis associated with
      acute parvovirus B19 infection.

PMID- 9564491
TI  - Transmission of multidrug-resistant Mycobacterium bovis to an immunocompetent
      patient.

PMID- 9564492
TI  - Microgranulomatous aspergillosis in a patient with chronic granulomatous disease:
      cure with voriconazole.

PMID- 9564493
TI  - Adenovirus cholecystitis in a patient with AIDS.

PMID- 9564494
TI  - Successful treatment of Trichosporon beigelii pneumonia with itraconazole.

PMID- 9564495
TI  - Candida tropicalis osteomyelitis: case report and review.

PMID- 9564496
TI  - Bacterial pneumonia due to Bordetella bronchiseptica in a patient with acute
      leukemia.

PMID- 9564497
TI  - Unusual presentation of tuberculous rheumatism (Poncet's disease) with oral
      ulcers and tuberculid.

PMID- 9564498
TI  - Disseminated Mycobacterium avium complex infection associated with bifocal
      synovitis in a patient with dermatomyositis.

PMID- 9564499
TI  - AIDS-associated atypical Pneumocystis carinii pneumonia revisited.

PMID- 9564501
TI  - Successful treatment of severe cytomegalovirus infection with ganciclovir in an
      immunocompetent host.

PMID- 9564500
TI  - Failure of amphotericin B lipid complex in the treatment of cutaneous
      leishmaniasis.

PMID- 9564502
TI  - Military tuberculosis with paradoxical expansion of intracranial tuberculomas
      complicating human immunodeficiency virus infection in a patient receiving highly
      active antiretroviral therapy.

PMID- 9564503
TI  - Biliary aspiration after administration of intravenous cholecystokinin for the
      diagnosis of hepatobiliary fascioliasis.

PMID- 9564504
TI  - Biliary tract infection due to bile-soluble bacteria: an intriguing paradox.

PMID- 9564506
TI  - Mycotic aneurysm due to Burkholderia pseudomallei.

PMID- 9564505
TI  - Acute respiratory failure associated with the human immunodeficiency virus (HIV)
      protease inhibitor indinavir in an HIV-infected patient.

PMID- 9564507
TI  - Furazolidone-induced mood disorder during the treatment of refractory giardiasis
      in a patient with AIDS.

PMID- 9564508
TI  - Life-threatening adverse event after amphotericin B lipid complex treatment in a
      patient treated previously with amphotericin B deoxycholate.

PMID- 9564509
TI  - Prosthetic joint infection due to Histoplasma capsulatum: case report and review.

PMID- 9564510
TI  - Hepatitis A vaccine and travel departure.

PMID- 9564511
TI  - Pneumocystis carinii pneumonia in patients with breast cancer: are there
      contributing local factors?

PMID- 9564512
TI  - Pneumocystis carinii: a versatile opportunist.

PMID- 9564513
TI  - Correcting the historical record: diagnosis and management of group A
      streptococcal pharyngitis.

PMID- 9564514
TI  - Double labeling with fluorescence in situ hybridization in Drosophila whole-mount
      embryos.

PMID- 9564515
TI  - Fluorescence in situ hybridization of cells on polyvinylidene fluoride membrane
      filters.

PMID- 9564516
TI  - Standardizing the counting of adipocytes in cell culture.

PMID- 9564517
TI  - Plasmid maintenance assay based on green fluorescent protein and FACS of
      mammalian cells.

PMID- 9564518
TI  - Fluorescent Escherichia coli C for enumeration of coliphages from environmental
      samples.

PMID- 9564519
TI  - Screening for recombinant E. coli using antibiotic test strips.

PMID- 9564520
TI  - Detergent and enzyme treatment of apoptotic cells for the observation of DNA
      fragmentation.

PMID- 9564521
TI  - Construction of a genomic DNA library by TA cloning.

PMID- 9564522
TI  - Generation of genomic mini-libraries by Taq DNA polymerase modification of
      genomic fragments.

PMID- 9564523
TI  - Small-scale preparation of the single-copy bacterial artificial chromosome vector
      pBeloBAC11.

PMID- 9564524
TI  - PCR amplification of cDNA libraries for cloning and screening.

PMID- 9564525
TI  - 3' RACE: skewed ratio of specific to general PCR primers improves yield and
      specificity.

PMID- 9564526
TI  - Distinct combination of purification methods dramatically improves cohesive-end
      subcloning of PCR products.

PMID- 9564527
TI  - Avoiding false positives in colony PCR.

PMID- 9564528
TI  - Digestion of terminal restriction endonuclease recognition sites on PCR products.

PMID- 9564529
TI  - Pitfalls of processed pseudogenes in RT-PCR.

PMID- 9564530
TI  - High-voltage and high-salt buffer facilitates electroporation of human aortic
      smooth-muscle cells.

PMID- 9564531
TI  - Efficient cloning of DAF polymorphic markers from silver-stained polyacrylamide
      gels.

PMID- 9564532
TI  - Efficient large-scale transformation of yeast.

PMID- 9564533
TI  - Comments on an article by M.P. Burton et al.

PMID- 9564534
TI  - Herpes simplex virus thymidine kinase-green fluorescent protein fusion gene: new
      tool for gene transfer studies and gene therapy.
AB  - Green fluorescent protein (GFP) and herpes simplex virus type-I thymidine kinase
      (TK) are commonly used markers in gene transfer studies. The latter gene has also
      proven to be an effective tool in cancer "suicide" gene therapy. To facilitate
      rapid and reliable selection of cells expressing TK, we constructed a plasmid
      expressing a TK-green fluorescent protein fusion gene (TK-GFP). In this fusion
      gene, the expression of each component is coupled to one another, permitting
      accurate determination of the percentage of cells expressing TK by detecting the
      green fluorescence produced by GFP. Transfection of the fusion plasmid to
      mammalian cells revealed that the construct is fully functional, making the cells
      both fluorescent and sensitive to ganciclovir.

PMID- 9564535
TI  - Quantitative RT-PCR amplification of RNA in single mouse oocytes and
      preimplantation embryos.
AB  - We describe a simple whole-cell method for quantitative reverse transcription
      (RT) PCR amplification of RNA that consistently allows the analysis of trace
      amounts of RNA, such as those carried by a fraction of a single mouse oocyte or
      preimplantation embryo, without organic extraction. The method is based on a
      preliminary genomic DNA digestion by DNase I in the presence of Mn++ and a
      subsequent RT step with rTth Reverse Transcriptase at 70 degrees C with the same
      buffer components, which also has the effect to irreversibly denature DNase I
      activity. Because of the completeness of genomic DNA digestion and RNA recovery,
      this procedure makes it possible to quantitatively amplify any target RNA,
      including those coded by intronless genes or genes whose intron-exon boundaries
      are unknown. By taking mRNAs of beta-actin, heat-shock protein HSP70.1 and
      ribosomal protein S16 as experimental models, we demonstrate the effectiveness of
      genomic DNA digestion by DNase I-Mn++ and of DNase I heat-denaturation and the
      quantitative properties of our method. We also show that this procedure is useful
      for transcriptional analyses during development that are hindered by paucity of
      biological material.

PMID- 9564536
TI  - Lac/Tet dual-inducible system functions in mammalian cell lines.
AB  - The Escherichia coli Lac repressor (Lac system) and tetracycline responsive
      promoter (Tet system) systems have been used individually to regulate gene
      expression at the cellular as well as the organismal levels. In this study, these
      two systems were combined (designated Lac/Tet dual-inducible system) to regulate
      two inducible genes simultaneously in a single cell. The isopropyl-beta-D
      thiogalactopyranoside (IPTG) and tetracycline (used for the operation of the Lac
      and the Tet systems) were non-cytotoxic to the cells when added together into the
      cells at around the optimal concentrations (IPTG: < or = 5 mM; tetracycline: <
      1.5 micrograms). The rate and efficiency of induction and repression of two
      inducible genes regulated by the Lac/Tet dual-inducible system were similar to
      the results obtained when one inducible gene is regulated by one inducible system
      in a single cell. The Lac/Tet dual-inducible system could function in many cell
      lines, which was demonstrated by regulating the expression of beta-galactosidase
      and luciferase reporter genes in five tumor cell lines by transient transfection
      analysis. The feasibility of introducing a second inducible system into an
      already established inducible cell line was confirmed. Finally, we showed that
      the Lac/Tet dual-inducible system functions at translational and at functional
      levels in a stable cell line named 7-4-b, which contains the Ha-ras and bc1-2
      inducible genes. In conclusion, this study extends the application of prokaryotic
      inducible systems from the regulation of a single gene to two genes and helps
      clarify the relationship between two genes and the effects of two genes on the
      cells.

PMID- 9564537
TI  - Establishment of a whole-chick sternum model that recapitulates normal cartilage
      development.
AB  - A serum-free organ culture model for chondrocyte maturation, using the Avian
      sternum, was developed. Day-14 chick embryo sterna were placed in organ culture
      in the presence of defined medium. The optimal medium for chondrocyte terminal
      differentiation contained specific concentrations of dexamethasone, insulin,
      thyroid hormone and ascorbic acid. Three parameters, including sternal growth,
      cell diameter and type X collagen production, were analyzed as indicators of
      chondrocyte terminal differentiation. These parameters were analyzed in cephalic,
      middle and caudal regions of the organ-cultured chick sterna and compared to
      sterna grown in ovo. This study demonstrates that the organ-cultured tissue
      maintains normal morphological characteristics and terminal differentiation in
      the cephalic region only, similar to in ovo development, while maintaining normal
      cell-matrix relationships.

PMID- 9564538
TI  - Vectors to target protein domains to different cellular compartments.
AB  - The pcDNA3 mammalian expression vector uses the cytomegalovirus (CMV) promoter to
      express proteins cloned into an adjacent polylinker. We have modified this vector
      to create three different targeting constructs: Go to Plasma Membrane (pGTM), Go
      to Nucleus (pGTN) and Go to Nucleus, Activate Transcription (pGTNAT). pGTM
      expresses a protein as a fusion to a myristic acid attachment signal, which
      targets proteins to the cell membranes. pGTN expresses an inserted protein as a
      fusion to a nuclear localization sequence (NLS), targeting it to the nucleus.
      pGTNAT incorporates an NLS (directing proteins to the nuclear compartment), an
      acid blob (a transcriptional activation domain) and a hemagglutinin epitope tag,
      creating a 107-amino acid fusion domain. We then cloned green fluorescent protein
      (GFP) into the three novel vectors and pcDNA3, and we transfected HeLa cells to
      test the new targeting constructs. Immunofluorescence analysis showed that the
      GFP protein localizes to the nucleus when over-expressed in pGTN and pGTNAT,
      localizes to the plasma membrane and perinuclear membrane when in pGTM and is
      ubiquitous through the cell in pcDNA3. We anticipate that these new vectors will
      prove very useful in future expression studies to examine the function of
      particular proteins when they are localized to specific cellular compartments.

PMID- 9564539
TI  - Intracellular magnetic labeling of lymphocytes for in vivo trafficking studies.
AB  - Lymphocyte adhesion and trafficking is difficult to observe in vivo over time. We
      used magnetic resonance imaging (MRI) to identify magnetically labeled
      lymphocytes in phantom experiments and in tissue. A method of lymphocyte labeling
      was developed that is based on fluid-phase endocytosis of nanometer-sized
      biocompatible superparamagnetic particles. The maximum cell uptake in culture was
      0.11 ng Fe/cell corresponding to 5 x 10(6) particles/lymphocyte. Cells stably
      retained the label and were fully viable for at least 3 days. Labeled lymphocytes
      showed adhesion to human endothelial cells similar to unlabeled cells, indicating
      no effect of labeling on cell surface expression of adhesion proteins. No
      particle-mediated cytotoxicity could be observed. The detection threshold of MRI
      for detecting labeled lymphocytes in the current study was 2.5 x 10(6) cells/30
      microL sampling volume. Following intravenous injection of labeled lymphocytes
      into rats, cells accumulated in spleen, lymph nodes and liver with a similar bio
      distribution as unlabeled cells. Lymphocyte accumulation in the spleen resulted
      in MRI signal intensity changes readily detectable by MRI. These findings suggest
      that intracellular lymphocyte labeling with superparamagnetic particles is
      feasible, does not alter the viability or tissue distribution of labeled cells
      and allows the detection of labeled lymphocytes by MRI.

PMID- 9564540
TI  - Reproducibility in the quantification of mRNA levels by RT-PCR-ELISA and RT
      competitive-PCR-ELISA.
AB  - The use of reverse transcription (RT) PCR for relative quantitation of gene
      transcripts relies on the reproducibility of the individual RT, PCR and product
      measurement steps. Semi-competitive RT-PCR (RT-cPCR) uses an internal competitor
      template in the PCR step to improve quantitation. We have surveyed the
      reproducibility of RT, PCR, RT-cPCR and measurement, amplifying the
      glyceraldehyde-3-phosphate dehydrogenase "housekeeping" gene from isolated renal
      glomeruli. We used an enzyme-linked immunosorbent assay (ELISA) to quantify PCR
      products. We also report our PCR-based method for constructing a competitor DNA
      identifiable independently of the native product. Our results show that the
      entire RT-PCR and ELISA process had a standard deviation (SD) of less than 10% (n
      = 10). This compared to an SD of less than 13% (n = 10) in PCR and ELISA. The SD
      for ELISA alone was less than 11% (n = 10). RT-cPCR quantitation gave an SD of
      approximately 15% (n = 10). These results support the use of standard RT-PCR for
      the relative quantitation of mRNA. RT-cPCR is also suited to relative
      quantitation, but it is also independent of the amplification saturation curve
      and permits the identification of differences in cellularity between samples.

PMID- 9564541
TI  - Retroviral gene transfer in chondrogenic limb bud micromass cultures.
AB  - We report development of a model of retroviral gene transduction in high-density
      limb bud cell micromass culture. The replication competent avian retrovirus RCAS
      BP (A) carrying the human placental alkaline phosphatase gene (RCAS AP) was used
      as a marker for retroviral infection and spread. The final protocol balances the
      need to allow time for retroviral integration and gene transduction against loss
      of chondrogenic potential when limb bud cells are plated at low density. It
      includes: (i) incubation of the dissociated limb bud cells with RCAS virus for 2
      h followed by low-density culture for 48 h to allow retroviral gene expression;
      and (ii) secondary replating as high-density micromass culture to initiate
      chondrogenesis. The pattern and level of chondrogenesis in the retrovirus
      transduced micromass cultures is similar to regular micromass cultures. At least
      40%-50% of cells express the retroviral-transduced genes 24 h after high-density
      plating. This new approach facilitates ectopic gene expression in micromass
      culture, enabling molecular dissection of chondrogenesis and serves as a model
      for gene transduction in other organotypic cultures.

PMID- 9564542
TI  - Diffusion of proteins across the nuclear envelope of HeLa cells.
AB  - We describe an experimental system to study nucleocytoplasmic diffusion of
      proteins in living HeLa cells. To localize proteins to the nucleus, substrates
      were created that contain a nuclear localization sequence fused to Aequorea
      victoria green fluorescent protein (GFP). Transiently and stably transfected HeLa
      cells were used for these assays. A protein of 29-kDa molecular mass that harbors
      GFP and the bipartite Xenopus nucleoplasmin nuclear localization sequence (NLS)
      accumulates efficiently in nuclei of HeLa cells. However, in the absence of
      active facilitated nuclear import, the reporter protein exits the nucleus and
      equilibrates between nucleus and cytoplasm. We define different conditions that
      promote the diffusion of small nuclear proteins across the nuclear envelope of
      mammalian culture cells. Our results set the stage to analyze the competence of
      nuclear pore complexes for nucleocytoplasmic diffusion of macromolecules in
      living cells.

PMID- 9564543
TI  - SDS agarose gels for analysis of proteins.
AB  - A new agarose-based protein electrophoresis gel system is described. The system
      consists of a highly resolving agarose, MetaPhor XR (FMC BioProducts, Rockland,
      ME, USA) dissolved in urea and TBE buffer and a stacking gel composed of a high
      gel-strength agarose, SeaKem Gold (FMC BioProducts). TBE containing sodium
      dodecyl sulfate (SDS) is used as electrophoresis buffer. The disadvantages of
      traditional agarose gels have been overcome, and several advantages over
      polyacrylamide gels have been demonstrated. The system is capable of high
      resolution separation of small proteins and has a dynamic separation range
      equivalent to a 4%-20% gradient polyacrylamide gel. Furthermore, the staining of
      protein bands by Coomassie Brilliant Blue is very uniform in this gel, and
      depending on the protein, higher detection sensitivity can be obtained compared
      to SDS polyacrylamide gels. In Western blotting, proteins are more efficiently
      transferred to the membrane from the agarose gel than from polyacrylamide gels.
      Finally, the exceptional stability of agarose allows for gels to be precast and
      stored for a year.

PMID- 9564544
TI  - Resurgence of carbon monoxide: an endogenous gaseous vasorelaxing factor.
AB  - Carbon monoxide (CO) is an endogenously generated gas that may play an important
      physiological role in the regulation of vascular tone. The CO-induced
      vasorelaxation, as a result of a direct action on vascular smooth muscles, has
      been demonstrated in many cases. Three major cellular mechanisms are proposed to
      explain the vasorelaxing effect of CO. These include the activation of soluble
      guanylyl cyclase, stimulation of various types of K channels, and inhibition of
      the cytochrome P450 dependent monooxygenase system in vascular smooth muscle
      cells. An interaction between CO and nitric oxide may also significantly
      contribute to the fine tuning of vascular tone. Furthermore, alterations in
      either the endogenous production of CO or the vascular responsiveness to CO have
      been encountered in several pathophysiological situations. A better understanding
      of the vascular effects of CO and the underlying cellular and molecular
      mechanisms will pave the way for the establishment of the role played by CO in
      vascular physiology and pathophysiology.

PMID- 9564545
TI  - Receptor-activating peptides distinguish thrombin receptor (PAR-1) and protease
      activated receptor 2 (PAR-2) mediated hemodynamic responses in vivo.
AB  - Vascular expression and cellular functions of the thrombin receptor (PAR-1) and
      protease activated receptor 2 (PAR-2) suggest similar but distinct vascular
      regulatory roles. The vascular actions of PAR-1 and PAR-2 in vivo were
      differentiated by monitoring mean arterial pressure (MAP) and heart rate (HR) of
      anesthetized mice in response to intravenous SFLLRN (0.1, 0.3, and 1 mumol/kg)
      and SLIGRL (0.1, 0.3, and 1 mumol/kg), the respective receptor-activating
      sequences for PAR-1 and PAR-2, and TFLLRNPNDK (0.3, 1, and 3 mumol/kg), a
      synthetic peptide selective for PAR-1. All peptides dose dependently decreased
      MAP (order of potency: SLIGRL > SFLLRN > TFLLRNPNDK). SLIGRL induced a more
      prolonged hypotension with a slow return to baseline, whereas SFLLRN- and
      TFLLRNPNDK-induced hypotension was followed by a rapid return towards baseline
      and a sustained moderate hypotension. SFLLRN and TFLLRNPNDK, but not SLIGRL,
      decreased HR. N omega-Nitro-L-arginine methyl ester HCl (L-NAME), an inhibitor of
      nitric oxide synthesis, attenuated the cumulative hypotensive response to SLIGRL
      but had no effect on the SFLLRN and TFLLRNPNDK hypotension. However, L-NAME
      revealed a rebound hypertension in response to SFLLRN and TFLLRNPNDK but not
      SLIGRL. In conclusion, activation of either PAR-1 or PAR-2 in vivo results in
      hypotension. In addition, only PAR-1 activation induced hypertension following L
      NAME, reflecting concurrent PAR-1-mediated vasoconstriction. Thus, these
      different hemodynamic responses in vivo suggest distinct physiological or
      pathophysiological roles for PAR-1 and PAR-2 in local vascular regulation.

PMID- 9564546
TI  - Prevention of stroke and preservation of the functions of cerebral arteries by
      treatment with perindopril in stroke-prone spontaneously hypertensive rats.
AB  - The aim of this study was to determine whether the prevention of stroke with
      perindopril treatment in stroke-prone spontaneously hypertensive rats (SHRSP) is
      associated with the preservation of the myogenic properties of the cerebral
      arteries. After weaning at 4 weeks of age, male SHRSP were fed a Japanese-style
      rat diet with high salt to induce stroke development. Treatment with perindopril
      was given by gavage every morning beginning at 6 weeks of age. There were three
      experimental groups: two groups treated with 4 mg.kg-1.day-1 perindopril for
      different durations (8 or 12 weeks) and one control group consisting of
      littermates given distilled water. All the control animals developed stroke and
      died within 14 weeks of age, and myogenic response of the middle cerebral
      arteries (MCA) to pressure increase was lost in these animals. In contrast, all
      the treated SHRSP survived during the treatment period, and myogenic response of
      the MCA was preserved. After withdrawal of the treatment, SHRSP treated for a
      longer period (12 weeks) also survived longer than those treated for a shorter
      period (8 weeks). The subsequent development of stroke and death following
      treatment withdrawal after 8 or 12 weeks of treatment was associated with the
      loss of pressure-dependent constriction in MCA. A longer treatment duration also
      increased the stiffness of the MCA, MCA from SHRSP after 12 weeks of treatment
      had smaller external and lumen diameters, and thicker walls than those from the 8
      week treatment group. In a separate study, we found that treatment of SHRSP with
      1 or 4 mg.kg-1.day-1 of perindopril for 24 weeks beginning at 6 weeks of age also
      protected them against death related to stroke, because these rats survived up to
      43 weeks of age, when the experiment was terminated. We conclude that there is an
      association between the absence of myogenic response in cerebral arteries and
      stroke development in SHRSP. Perindopril treatment preserves the myogenic
      response of MCA in SHRSP and prevents the stroke development in these animals. A
      prolonged treatment could increase the survival of SHRSP through a remodelling of
      the MCA and increasing the stiffness of the cerebral arteries.

PMID- 9564547
TI  - Vascular endothelial dysfunction contributes to myocardial depression in ischemia
      reperfusion in the rat.
AB  - Endocardial and vascular myocardial capillary endothelium has been shown to
      modulate the contractile characteristics of myocardium by altering myofibrillar
      affinity for calcium. Although the release of endothelial-derived substances that
      modify myocardial contractility has been shown to be altered in certain
      physiologic and pathologic situations, until now no study has evaluated whether
      the direct modulatory effects of endothelium on its subjacent myocardium were
      altered in pathologic situations and contributed to loss of contractile function.
      This study was designed to evaluate whether the direct contractile modulatory
      effects of endocardial and (or) vascular endothelium were altered and whether
      these alterations contributed to contractile dysfunction in a model of ischemia
      reperfusion. Sixty-two perfused rat hearts as Langendorff preparations were
      randomized to no intervention, intracoronary Triton X100 injection (to render
      vascular endothelium dysfunctional), ischemia (30 min)-reperfusion (20 min), and
      ischemia-reperfusion followed by intracoronary Triton X100 injection. Coronary
      endothelial-dependent vascular reactivity and vascular smooth muscle reactivity
      were assessed by serotonin and sodium nitroprusside, respectively. Myocardial
      damage was assessed by coronary effluent creatine phosphokinase and by
      morphologic studies. Papillary muscles were then excised and contractile
      characteristics evaluated at varying extracellular calcium concentration prior to
      and after endocardial endothelial removal with Triton X100. All three
      interventions eliminated all coronary vascular response to serotonin but did not
      modify response to nitroprusside. Creatine phosphokinase values rose only in
      hearts with ischemia-reperfusion, and only minor morphologic changes occurred,
      mostly in hearts with ischemia-reperfusion. Papillary muscles from hearts with
      intracoronary Triton X100 injection had lower contractile indices compared with
      normal controls (total tension 4.0 vs. 4.6 g/mm2, p < 0.01) and an abbreviation
      of contraction duration. Increasing extracellular calcium concentration from to
      0.7 to 3.25 mM eliminated these differences. Similar but more marked decreases in
      contractile indices and twitch duration were noted in the two ischemia
      reperfusion groups, but consistent with some myocardial damage being present,
      increasing extracellular calcium concentration to 3.25 or 7 mM did not fully
      eliminate these differences. In both ischemia-reperfusion groups and the
      intracoronary Triton X100 group, the relative increase in total tension with
      increasing extracellular calcium concentrations was similar (35 to 38%) and
      greater than that of the control group (25%), consistent with dysfunction of
      vascular endothelium contributing to myocardial dysfunction in the three
      intervention groups. Endocardial endothelial removal had a similar effect in all
      four groups, suggesting that dysfunction of endocardial endothelium does not play
      a role in this model. We conclude that vascular but not endocardial endothelial
      dysfunction contributes to the myocardial dysfunction that occurs during ischemia
      reperfusion injury.

PMID- 9564548
TI  - Effects of propofol and pentobarbital on ligand binding to GABAA receptors
      suggest a similar mechanism of action.
AB  - The GABAA receptor is allosterically modulated by a number of anesthetics and
      barbiturates. We have examined the effects of propofol and pentobarbital on the
      binding of the receptor agonist [3H]muscimol and the benzodiazepine modulators
      [3H]flunitrazepam and [3H]Ro15-4513 to bovine brain membranes. Both agents
      potentiated the binding of [3H]muscimol (5 nM), with EC50 values of 18.7 and 276
      microM, respectively. The binding of [3H]muscimol is heterogeneous, suggesting
      the presence of both high (Kd approximately 10 nM) and low (Kd approximately 0.1
      1.0 microM) affinity sites. The major effect of both propofol and pentobarbital
      was to increase the affinity of the lower affinity sites without changing the
      total binding capacity. In contrast, the steroid anesthetic alphaxalone did not
      affect the affinity of these sites, suggesting that this drug has distinct
      effects on the GABAA receptor. Propofol and pentobarbital also increased the
      binding of the benzodiazepine agonist [3H]flunitrazepam and decreased the binding
      of the inverse agonist [3H]Ro15-4513. The results of these studies demonstrate
      that propofol and pentobarbital modulate the binding of ligands to the GABAA
      receptor in a similar manner, suggesting that these drugs may have a common
      mechanism of action.

PMID- 9564549
TI  - Correlation between cardiac remodelling, function, and myocardial contractility
      in rat hearts 5 weeks after myocardial infarction.
AB  - Early after infarction, ventricular dysfunction occurs as a result of loss of
      myocardial tissue. Although papillary muscle studies suggest that reduced
      myocardial contractility contributes to this ventricular dysfunction, in vivo
      studies indicate that at rest, cardiac output is normal or near normal,
      suggesting that contractility of the remaining viable myocardium of the
      ventricular wall is preserved. However, this has never been verified. To explore
      this further, 100 rats with various-sized myocardial infarctions had ventricular
      function assessed by Langendorff preparation or by isolated papillary muscle
      studies 5 weeks after infarction. Morphologic studies were also done. Rats with
      large infarctions (54%) had marked ventricular dilatation (dilatation index from
      0.23 to 0.75, p < 0.01) and papillary muscle dysfunction (total tension from 6.7
      to 3.2 g/mm2, p < 0.01) but only moderate left ventricular dysfunction (maximum
      developed tension from 206 to 151 mmHg (1 mmHg = 133.3 Pa), p < 0.01), a decrease
      less than one would expect with an infarct size of 54%. The contractility of the
      remaining viable myocardium of the ventricle was also moderately depressed (peak
      systolic midwall stress 91 to 60 mmHg, p < 0.01). Rats with moderate infarctions
      (32%) had less marked but still moderate ventricular dilatation (dilatation index
      0.37, p < 0.001) and moderate papillary muscle dysfunction (total tension 4.2
      g/mm2, p < 0.01). However, their decrease in ventricular function was only mild
      (maximum developed pressure 178 mmHg, p < 0.01) and less than one would expect
      with an infarct size of 32%. The remaining viable myocardium of the ventricular
      wall appeared to have normal contractility (peak systolic midwall stress = 86
      mmHg, ns). We conclude that in this postinfarction model, in large myocardial
      infarctions, a loss of contractility of the remaining viable myocardium of the
      ventricular wall occurs as early as 5 weeks after infarction and that papillary
      muscle studies slightly overestimate the degree of ventricular dysfunction. In
      moderate infarctions, the remaining viable myocardium of the ventricular wall has
      preserved contractility while papillary muscle function is depressed. In this
      relatively early postinfarction phase, ventricular remodelling appears to help
      maintain left ventricular function in both moderate and large infarctions.

PMID- 9564550
TI  - Effect of chronic NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure and
      renal function in conscious uninephrectomized spontaneously hypertensive rats.
AB  - We have studied during 30 days the effect of a low dose of NG-nitro-L-arginine
      methyl ester (1 mg.kg-1.day-1 in drinking water) in the presence of D- or L
      arginine (1 mg.kg-1.day-1 in drinking water) in comparison with D- or L-arginine
      alone on blood pressure and renal function in conscious uninephrectomized female
      spontaneously hypertensive rats. At the end of the study, there was a significant
      increase in systolic blood pressure in the NG-nitro-L-arginine methyl ester + D
      arginine group (307 +/- 6 mmHg (1 mmHg = 133.3 Pa), n = 14, p < 0.05) in
      comparison with NG-nitro-L-arginine methyl ester + L-arginine (281 +/- 6 mmHg, n
      = 14), L-arginine (262 +/- 5 mmHg, n = 13), and D-arginine (258 +/- 7 mmHg, n =
      12) groups. There were no changes in diuresis, proteinuria, or sodium and
      potassium excretion between differently treated animals during this study. These
      results suggest that in uninephrectomized female spontaneously hypertensive rats,
      after 1 month blockade of NO synthesis with a low dose of NG-nitro-L-arginine
      methyl ester, vasculature is under tonic control by NO and it is not correlated
      with renal dysfunction.

PMID- 9564551
TI  - Physiological characteristics of identified motor units in the mouse extensor
      digitorum longus muscle: an in vitro approach.
AB  - Physiological, histochemical, and morphometric properties of fast-twitch single
      motor units were studied in mouse extensor digitorum longus muscles in an in
      vitro ventral root-nerve-muscle preparation. Single motor units were functionally
      isolated by microdissection of the ventral root, and the glycogen depletion
      technique was used to demonstrate the component muscle fibers. Monoclonal
      antibodies were used to identify their myosin heavy chain composition. The
      technique allows one to correlate physiological characteristics of single motor
      units with fiber type but is less useful for morphological assessment of motor
      unit size as a result of failure to deplete glycogen from all fibers of motor
      units containing fibers with high oxidative capacity.

PMID- 9564552
TI  - Vascular wall reactivity in conductance and resistance arteries: differential
      effects of insulin resistance.
AB  - Insulin resistance is associated with an increased risk of cardiovascular disease
      that is probably related to abnormalities of vascular wall function. The JCR:LA
      cp rat is a unique animal model of human vascular disease that exhibits a
      profound insulin resistance, vasculopathy, and cardiovascular disease, and allows
      study of the relationships between insulin resistance and vascular function.
      Conductance and resistance arteries serve different functions, thus vascular
      disease may affect these types of artery differently. Concentration-response
      curves to norepinephrine, phenylephrine, and acetylcholine were studied in
      conductance vessels (aortic rings) and resistance vessels (mesenteric arteries)
      from 12-week-old male obese and lean JCR:LA-cp rats. The aortic rings and
      mesenteric arteries from obese rats showed increased maximal response to
      phenylephrine compared with those from lean rats, whereas only the mesenteric
      arteries from obese rats showed increased maximal response to norepinephrine. In
      aortic rings, relaxation to acetylcholine was similar for both genotypes, but the
      mesenteric arteries of obese rats showed impaired relaxation to acetylcholine. We
      conclude that the sensitivity to vasoconstriction is enhanced in aortic rings and
      mesenteric arteries of obese male JCR:LA-cp rats, but endothelial function is
      impaired only in the mesenteric resistance arteries of these animals. Hence
      functional aberrations in the obese, insulin-resistant state are more pronounced
      in mesenteric resistance arteries than in a major conductance artery.

PMID- 9564553
TI  - Comparison between the CEDIA and EMIT II immunoassays for the determination of
      benzodiazepines.
AB  - We evaluated a new, qualitative immunoassay for benzodiazepines in urine using
      CEDIA technology on the Hitachi 747 and compared its performance to an
      immunoassay using EMIT II methodology on the same instrument. A total of 500
      urine samples received for routine drug screen analysis were prospectively
      examined for benzodiazepines by both methods. Samples producing positive results
      by either immunoassay method were analyzed by gas chromatography-mass
      spectrometry (GC-MS). Available medical records were reviewed for patients whose
      samples produced discrepant immunoassay results or that were positive in both
      immunoassays but negative by GC-MS. Samples that produced negative results in
      both immunoassays were not subjected to GC-MS analysis. Therefore, identification
      of an immunoassay result as a false negative only occurred when the sample
      produced a positive value in only one of the two immunoassays and was confirmed
      as positive by either GC-MS or medical record review. Following initial
      immunoassay screening and confirmation by GC-MS, a medical record review and
      reanalysis of GC-MS data was performed. After this in-depth analysis of the data,
      the CEDIA method produced 60 true-positives, 7 false positives and no false
      negatives. The EMIT II method produced 47 true positives, 1 fase positive and 13
      false negatives. These differences appear to be due to the CEDIA assay being more
      sensitive for detection of lorazepam.

PMID- 9564554
TI  - Liver-type arginase in serum during and after liver transplantation: a novel
      index in monitoring conditions of the liver graft and its clinical significance.
AB  - We quantified liver-type arginase in sera of 47 patients undergoing partial liver
      transplantation with use of an ELISA method. The level of liver-type arginase
      fluctuated slightly beyond the normal range in successful liver recipients, while
      it changed more drastically or precipitously in unsuccessful ones, accompanying
      or unaccompanying elevation of AST and ALT levels. A higher elevation pattern of
      the arginase level (above 100 ng ml-1) was observed in each of the unsuccessful
      recipients with critical condition, except for one patient. Other hepatic markers
      (LDH, ALP, and T-BIL) remained relatively unchanged until the terminal stage of
      deceasing patients. The finding that the liver-type arginase emerged in large
      quantity in the blood stream immediately after reperfusion of the liver graft
      indicates that the enzyme leaks out of hepatocytes damaged, presumably, by
      storage in the absence of circulation. A half-life of the liver-type arginase in
      the human blood was estimated to be 1 h, that is clearly shorter than that of
      AST. The short half-life of the arginase appears to be ascribable, at least
      partly, to formation of an immune complex with circulating autoantibody which
      appears in many liver recipients. These results suggest that liver-type arginase
      behaves uniquely in the serum among many hepatic enzymes, and could serve as a
      distinct marker of hepatic lesions, particularly during and after liver
      transplantation.

PMID- 9564555
TI  - A commercial pregnancy test modified for field studies of fetal loss.
AB  - We describe simple modifications to the ICON II hCG (URINE) pregnancy test to
      provide a sensitive and specific urinary assay for hCG in field studies of fetal
      loss. The modified assay had a qualitative lower limit of detection of 0.30 IU/l,
      a 50% qualitative limit of 0.61 IU/l, a 100% qualitative limit of 1.16 IU/l, and
      a quantitative limit of 0.80 IU/l. Coefficients of variation ranged from 9.9% to
      21.1%. Parallelism was observed among serially diluted subject samples. We used
      the assay in an 11-month prospective study of fetal loss in rural Bangladesh in
      which urine samples were collected twice-weekly from 494 women; 330 pregnancies
      and 93 fetal losses were detected. The median time to a positive pregnancy
      diagnosis was day 26 from last menses. The modified assay provided qualitative
      detection of early pregnancy comparable to laboratory assays, and appears to be
      well suited for use in epidemiologic or rural-population fetal loss studies.

PMID- 9564556
TI  - Proteinases and proteinase inhibitors during the development of pulmonary
      fibrosis in rat.
AB  - Changes in the activities of several proteinases and their inhibitors were
      investigated during the development of bleomycin-induced pulmonary fibrosis in
      rat. Studies on the proteinase-anti-proteinase-ratio may contribute to the
      understanding of the mechanism of the development of pulmonary fibrosis and may
      help to develop therapeutic strategies to prevent tissue damage by proteolytic
      attack. In the acute inflammatory period the activity of metalloelastase in lung
      tissue increased by about 10-fold. The time course of changes in the activity of
      72 kD gelatinase indicates that this gelatinase accounts at least partially for
      the elastolytic activity. Elastase inhibitory activity in lung tissue showed
      maxima at days 1 and 5 and high levels in the fibrotic phase. The increase of the
      elastase inhibitory activity at the beginning of the fibrotic period corresponds
      with elevated activity of alpha 2-macroglobulin. Alveolar fluid and alveolar
      macrophages did not contain elastase activity but contained high elastase
      inhibitory activity. During the period of chronic inflammation, the activities of
      the cathepsins L, B, H and S in lung tissue and in isolated alveolar macrophages
      were found to be strongly increased.

PMID- 9564557
TI  - Annual rhythmic variations of follitropin, lutropin, testosterone and sex-hormone
      binding globulin in men.
AB  - The annual rhythmic variations of the serum concentrations of follitropin,
      lutropin, sex-hormone-binding globulin and testosterone, the ratio between the
      serum concentrations of testosterone and sex-hormone-binding globulin, and the
      salivary concentration of testosterone were investigated in a group of 20
      apparently healthy men. Venous blood and salivary specimens were collected at 1
      month intervals during 12 months. The annual rhythms were studied by using a
      periodic function resulting from the sum of three cosine functions with periods
      of 365, 182.5 and 121.66 days. For the salivary concentration of testosterone and
      for the ratio between the serum concentrations of testosterone and sex-hormone
      binding globulin, only the cosine function with a period of 365 days was
      significant, and for the serum concentration of lutropin, only the cosine
      function with a period of 121.66 days was significant. Serum concentrations of
      follitropin, sex-hormone-binding globulin and testosterone were significantly
      affected by 365 and 121.66 rhythmic components. The salivary concentration of
      testosterone and the serum concentration of follitropin are the quantities with
      the greatest annual rhythmic variation of those studied.

PMID- 9564558
TI  - Genetic heterogeneity of the 5' uncoding region of the catalase gene in Hungarian
      acatalasemic and hypocatalasemic subjects.
AB  - The 5' uncoding region (165 bp), exon 1 (63 bp) and part of intron 1 (20 bp) of
      the catalase gene was amplified by PCR in acatalasemic (2), hypocatalasemic (19)
      patients and healthy individuals (10). The single strand conformational
      polymorphism of PCR products showed a highly polymorphic pattern. This
      polymorphism was supported by nucleotide sequence analyses yielding eight
      mutations. They are A to T, C to A and C to T at positions -21, -20, -18 of the
      5' flanking region, T to C at positions 4, 44, 49 of the non-coding region and C
      to T and C to A at positions 12, 27 of exon 1. Of these nucleotide substitutions,
      the fourth, fifth, seventh and eighth are novel mutations. The mutations 1, 3, 6,
      8 were present at least at heterozygous level in all acatalasemics and
      hypocatalasemics. None of these mutations may be the causal mutation(s) of
      acatalasemia as each of these nucleotide substitutions were detected in healthy
      subjects with normal blood catalase activity.

PMID- 9564559
TI  - Modification of serum apolipoprotein A-I, apolipoprotein B and lipoprotein(a)
      levels after bisphosphonates-induced acute phase response.
AB  - Lipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle displaying
      strong atherothrombotic properties. Although the concentration of Lp(a) in plasma
      is under strong genetic regulation, there are emerging evidences that several
      other factors, such as hormonal disorders, acute phase, liver and renal failure
      may affect its metabolism. The aim of the present study was to investigate
      whether bisphosphonates, an effectual drug in the treatment of malignant
      hypercalcemia and Paget's disease of bone, known to induce a concomitant acute
      phase, may have a significant influence on Lp(a) concentrations. Nine subjects
      (four men and five women), with plasma Lp(a) concentrations in the range between
      6.4 and 17.7 mg/dl, were subjected to a single intravenous infusion of
      bisphosphonates (7.5 mg of aminohydroxybutylidene and 5.0 mg of
      aminohydroxylidene), previously dissolved in 250 ml of saline. Lp(a), apo A-I,
      apo B, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were
      measured at the baseline and after days one, two, four and seven. CRP, ESR and
      Lp(a) started to increase after two days from the treatment, reaching statistical
      significance after day two, four and seven, respectively. Apo B and apo A-I
      decreased significantly after days one and two, respectively. Although patterns
      and relative amounts of the increase of CRP were substantially different among
      the subjects studied, the increase of Lp(a) was more homogeneous; the peak of
      Lp(a) concentrations was reached only seven days after treatment in the group as
      a whole, in agreement with previous observations. In univariate regression
      analysis, significant correlations were found only between apo A-I and ESR, and
      apo A-I and Lp(a). The present study suggest that Lp(a) behaves as an acute phase
      protein. Besides, we observed a slight but significant decrease of apo A-I and
      apo B after administration of bisphosphonates.

PMID- 9564560
TI  - Molecular genetic analysis of the Prader-Willi syndrome by using fluorescent
      multiplex PCR of the dinucleotide repeats on chromosome 15q11-q13.

PMID- 9564561
TI  - Increased lipoprotein susceptibility to oxidation following long distance running
      in trained subjects.

PMID- 9564562
TI  - Multiple and simultaneous phenotyping tests: beware of ascorbic acid when
      determining the mephenytoin (S)/(R) ratio.

PMID- 9564564
TI  - Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and
      biology and development of tissue cysts.
AB  - Infections by the protozoan parasite Toxoplasma gondii are widely prevalent world
      wide in animals and humans. This paper reviews the life cycle; the structure of
      tachyzoites, bradyzoites, oocysts, sporocysts, sporozoites and enteroepithelial
      stages of T. gondii; and the mode of penetration of T. gondii. The review
      provides a detailed account of the biology of tissue cysts and bradyzoites
      including in vivo and in vitro development, methods of separation from host
      tissue, tissue cyst rupture, and relapse. The mechanism of in vivo and in vitro
      stage conversion from sporozoites to tachyzoites to bradyzoites and from
      bradyzoites to tachyzoites to bradyzoites is also discussed.

PMID- 9564565
TI  - Clinical and microbiological aspects of Trichomonas vaginalis.
AB  - Trichomonas vaginalis, a parasitic protozoan, is the etiologic agent of
      trichomoniasis, a sexually transmitted disease (STD) of worldwide importance.
      Trichomoniasis is the most common nonviral STD, and it is associated with many
      perinatal complications, male and female genitourinary tract infections, and an
      increased incidence of HIV transmission. Diagnosis is difficult, since the
      symptoms of trichomoniasis mimic those of other STDs and detection methods lack
      precision. Although current treatment protocols involving nitroimidazoles are
      curative, metronidazole resistance is on the rise, outlining the need for
      research into alternative antibiotics. Vaccine development has been limited by a
      lack of understanding of the role of the host immune response to T. vaginalis
      infection. The lack of a good animal model has made it difficult to conduct
      standardized studies in drug and vaccine development and pathogenesis. Current
      work on pathogenesis has focused on the host-parasite relationship, in particular
      the initial events required to establish infection. These studies have
      illustrated that the pathogenesis of T. vaginalis is indeed very complex and
      involves adhesion, hemolysis, and soluble factors such as cysteine proteinases
      and cell-detaching factor. T. vaginalis interaction with the members of the
      resident vaginal flora, an advanced immune evasion strategy, and certain stress
      responses enable the organism to survive in its changing environment. Clearly,
      further research and collaboration will help elucidate these pathogenic
      mechanisms, and with better knowledge will come improved disease control.

PMID- 9564567
TI  - Diagnosis of infectious diseases: a cytopathologist's perspective.
AB  - This review explores the role of the cytopathology laboratory in the detection
      and presumptive identification of microorganisms. Sample procurement by
      exfoliation, abrasion, and aspiration techniques, as well as a variety of
      cytopreparatory and staining methods, is reviewed. Emphasis is placed on the
      utility of fine-needle aspiration as a rapid, safe, and cost-effective
      diagnositic procedure. The role of rapid interpretation and specimen triage is
      also discussed. Cytomorphologic features and staining characteristics are
      presented for a spectrum of microorganisms potentially encountered in the
      cytopathology laboratory. Pitfalls in diagnosis and the usefulness of special
      stains and ancillary techniques are also evaluated. The importance of
      communication, collaboration, and clinical correlation is stressed.

PMID- 9564566
TI  - Use of enzyme tests in characterization and identification of aerobic and
      facultatively anaerobic gram-positive cocci.
AB  - The contribution of enzyme tests to the accurate and rapid routine identification
      of gram-positive cocci is introduced. The current taxonomy of the genera of
      aerobic and facultatively anaerobic cocci based on genotypic and phenotypic
      characterization is reviewed. The clinical and economic importance of members of
      these taxa is briefly summarized. Tables summarizing test schemes and kits
      available for the identification of staphylococci, enterococci, and streptococci
      on the basis of general requirements, number of tests, number of taxa, test
      classes, and completion times are discussed. Enzyme tests included in each scheme
      are compared on the basis of their synthetic moiety. The current understanding of
      the activity of enzymes important for classification and identification of the
      major groups, methods of testing, and relevance to the ease and speed of
      identification are reviewed. Publications describing the use of different
      identification kits are listed, and overall identification successes and problems
      are discussed. The relationships between the results of conventional biochemical
      and rapid enzyme tests are described and considered. The use of synthetic
      substrates for the detection of glycosidases and peptidases is reviewed, and the
      advantages of fluorogenic synthetic moieties are discussed. The relevance of
      enzyme tests to accurate and meaningful rapid routine identification is
      discussed.

PMID- 9564568
TI  - Zoonotic filariasis.
AB  - Filariae of animals, especially those of mammals, often infect humans and
      typically produce cryptic infections. These "zoonotic" infections have been
      reported from virtually all parts of the world including temperate zones.
      Infections may be symptomatic or not, and the parasites are found in surgical
      tissue biopsy specimens or, more rarely, are removed intact from superficial
      sites such as the orbit or conjuctivae. Typically, these worms tend to occupy
      tissue sites similar to those occupied in the natural animal host, with the
      exception of the eyes. Many kinds of filariae have been isolated from humans,
      including species of Dirofilaria, Brugia, Onchocerca, Dipetalonema, Loaina and
      Meningonema. Worms have been found in subcutaneous tissues, the heart and lungs,
      lymphatics, the eye, and the central nervous system. Specific identification of
      these filariae is based on their morphological features in histologic sections.
      Unfortunately, some of these worms cannot be identified even at the generic
      level. There are other species of filariae, presumed to be zoonotic, which
      produce patent infections in humans but are poorly and incompletely known. These
      include Microfilaria semiclarum and Microfilaria bolivarensis. It is probable
      that almost any filaria parasitizing animals can, under proper circumstances,
      infect humans and undergo some degree of development. Undoubtedly, additional
      species of filariae will continue to be isolated from humans in the future.

PMID- 9564570
TI  - The Web, Communication Trends, and Children's Health. Part 2: The Web and the
      practice of pediatrics.
AB  - This article, Part 2 of a five-part series on The Web, Communications Trends, and
      Children's Health, describes how the Web's "virtual library" lets pediatricians
      tap into an evergrowing body of resources, including the latest medical
      information and online Continuing Medical Education. In addition, the Web creates
      new ways to practice pediatrics and share patient information.

PMID- 9564571
TI  - Clinical characteristics of an apparent life-threatening event (ALTE) and the
      subsequent occurrence of prolonged apnea or prolonged bradycardia.
AB  - The objective of this study was to test the hypothesis that the characteristics
      of an apparent life-threatening event (ALTE) influence the risk for a subsequent
      episode of prolonged apnea or bradycardia. Data were obtained from 182 infants
      referred because of an apparent life-threatening event who were followed up at
      home for 2 lunar months on an apnea/bradycardia monitor with recording
      capability. A prolonged episode was defined as apnea > or = 20 sec long or an
      episode of bradycardia > or = 10 sec in duration as validated and measured from
      the event recordings. Seventeen percent of infants had at least one episode of
      prolonged apnea or prolonged bradycardia. Change in skin color, degree of
      resuscitative intervention, and behavioral state were not statistically
      significant factors influencing the risk of a subsequent prolonged episode.
      Contrary to clinical expectation, a significantly greater percentage of infants
      subsequently had a prolonged episode whose muscle tone was described as normal
      during the ALTE (24.0%), when compared with those infants whose ALTE was
      associated with limpness or increased muscle tone (9.3%). The coexistence of
      gastroesophageal reflux did not influence the overall results. The observations
      in this study place in question the clinical approach of relying on the detailed
      characteristics of an ALTE in determining the need for follow-up studies and/or
      home monitoring.

PMID- 9564572
TI  - Gastrointestinal complications of chronic granulomatous disease: case report and
      literature review.
AB  - Chronic granulomatous disease (CGD), an inherited disorder of phagocytic
      leukocyte function, is characterized by recurrent infections with catalase
      positive organisms. Gastrointestinal (GI) tract involvement, present in the
      majority of affected individuals, may be present initially and recurrently,
      mimics other entities such as inflammatory bowel disease, and causes substantive
      morbidity and mortality. Disorders of motility, ulceration, obstruction, and
      infection (e.g., abscesses) occur from the mouth to the anus and stereotypically
      manifest with vomiting, diarrhea, abdominal pain, weight loss, and fever. Careful
      physical examination, in concert with appropriate diagnostic studies, is
      necessary to delineate intraabdominal pathologic processes. Abdominal
      radiographs, ultrasonography, computerized tomography, and endoscopy are useful
      ancillary diagnostic procedures. Drainage of accessible abscesses, antimicrobial
      therapy based on organisms cultured from blood and tissue, and interferon gamma
      may lead to suppression or eradication of infections and resolution of symptoms.
      Corticosteroids are useful for gastric outlet obstruction and sulfasalazine and
      cyclosporine for large bowel disease. Gallbladder dysfunction may be ameliorated,
      as in our patient, with administration of cholestyramine.

PMID- 9564573
TI  - Respiratory health, lung function, and airway responsiveness in school-age
      survivors of very-low-birth-weight.
AB  - The purpose of this study was to determine the respiratory symptoms, pulmonary
      function, and airway reactivity in school-age survivors of very-low-birth-weight
      and to describe the influence of birth weight and perinatal illness on their
      pulmonary function. Thirty (of 39) 10- to 11-year-old survivors of very-low-birth
      weight (VLBW) recruited at birth into a prospective longitudinal study of
      development; 30 (of 32) normal-birth-weight peers recruited from the same school
      or census tract as the VLBW group at age 5; and 15 normal-birth-weight siblings
      of the VLBW group participated in the study. Outcome measures were mother's
      reports of respiratory health; forced vital capacity (FVC), forced expiratory
      volume in 1 second (FEV1); FEV1/FVC; forced expiratory flow, midexpiratory phase
      (FEF25-75); peak expiratory flow rate (PEFR); and tolerance to methacholine.
      There were no differences between groups in mothers' reports of current
      respiratory health. Pulmonary function values were lower for the VLBW survivors
      but significant only for FEF25-75 (F = 4.13; P = 0.02). Number of days in the
      intensive care nursery correlated significantly with decreased FEV1 (r = -.40, df
      = 28, P = 0.03), FEV1/FVC (r = -.37, df = 28, P = 0.04, and FEF25-75 (r = -.39,
      df = 28, P = 0.03). Only the relationship between length of nursery stay and
      FEV1/FVC was independent of birth weight. Number of days on mechanical
      ventilation was significantly correlated with decreased FEV1 (-.44, df = 28, P =
      0.01), FEV1/FVC (r = -.38, df = 28, P = 0.04), FEF25-75 (r = -.44, df = 28, P =
      0.01, and PEFR (r = -.40, df = 28, P = 0.03). All of these relationships were
      independent of birth weight. There were no significant associations between
      perinatal risk factors and methacholine responsiveness. Differences between VLBW
      children and normal-birth-weight children in pulmonary function are modest even
      when statistically significant. Severity of perinatal illness influences
      pulmonary function parameters into late childhood.

PMID- 9564569
TI  - Clinical, cellular, and molecular factors that contribute to antifungal drug
      resistance.
AB  - In the past decade, the frequency of diagnosed fungal infections has risen
      sharply due to several factors, including the increase in the number of
      immunosuppressed patients resulting from the AIDS epidemic and treatments during
      and after organ and bone marrow transplants. Linked with the increase in fungal
      infections is a recent increase in the frequency with which these infections are
      recalcitrant to standard antifungal therapy. This review summarizes the factors
      that contribute to antifungal drug resistance on three levels: (i) clinical
      factors that result in the inability to successfully treat refractory disease;
      (ii) cellular factors associated with a resistant fungal strain; and (iii)
      molecular factors that are ultimately responsible for the resistance phenotype in
      the cell. Many of the clinical factors that contribute to resistance are
      associated with the immune status of the patient, with the pharmacology of the
      drugs, or with the degree or type of fungal infection present. At a cellular
      level, antifungal drug resistance can be the result of replacement of a
      susceptible strain with a more resistant strain or species or the alteration of
      an endogenous strain (by mutation or gene expression) to a resistant phenotype.
      The molecular mechanisms of resistance that have been identified to date in
      Candida albicans include overexpression of two types of efflux pumps,
      overexpression or mutation of the target enzyme, and alteration of other enzymes
      in the same biosynthetic pathway as the target enzyme. Since the study of
      antifungal drug resistance is relatively new, other factors that may also
      contribute to resistance are discussed.

PMID- 9564574
TI  - Postdural puncture headache in pediatric oncology patients.
AB  - This prospective cohort study determined the incidence and risk factors for
      development of postdural puncture headache (PDPH) in children after lumbar
      puncture (LP). Eighty-six children were enrolled. LPs were performed with use of
      22-gauge spinal needles with the bevel oriented parallel to the long axis of the
      spine. Follow-up telephone interviews and patients' diary of symptoms were
      collected. Headache brought on by sitting up and relieved by lying down was
      defined as PDPH. Of the 80 who completed the study, six (8%) developed PDPH. Two
      (3%) were less than 6 years old and four (5%) were 6 to 12 years of age. Children
      with a history of headache following a previous LP were nine times as likely to
      experience PDPH. PDPH occurs not infrequently in children. A prior history of
      headache is a predisposing factor.

PMID- 9564576
TI  - A child with recurrent meningitis.

PMID- 9564575
TI  - Colonic polyps in children: frequently multiple and recurrent.
AB  - A retrospective chart review on 77 children and adolescents (45 males and 32
      females) with colorectal polyps seen over a 15-year period (1980-1994) was
      undertaken. Their presenting symptoms, demographic data, methods of diagnosis,
      pathologic diagnosis, and outcome were assessed. The age at presentation varied
      from 6 months to 19 years (mean age 77 months), 66.2% presenting under 6 years of
      age. The presenting symptoms were rectal bleeding in 71 patients, mass per rectum
      in 12, abdominal pain in nine, diarrhea in nine, vomiting in two, and one patient
      was asymptomatic. Air contrast barium enema was confirmatory in 41/54 patients
      (76%). Polyps were palpable in 16 patients during the rectal examination. A
      single polyp was present in 50 patients, whereas two to five polyps were present
      in 20 patients, and more than five in seven patients. Successful endoscopic
      removal was accomplished in 71/73 patients (97.3%). In 83.1% of patients polyps
      were located in the rectosigmoid area and in 32.5% polyps occurred proximal to
      the sigmoid colon. However, multiple polyps in the same location or at other
      locations were also present simultaneously. Recurrence was observed in five of 63
      patients (7.9%) with juvenile polyps, in one patient with infantile polyposis,
      and in one with solitary adenomatous polyp. We conclude that a full colonoscopic
      evaluation should be performed in all patients with suspected polyps if feasible,
      for multiple polyps occurred in 35% of children without polyposis syndromes in
      this series. Parents of patients with more than three polyps and/or a family
      history of juvenile polyposis should be warned regarding the possibility of an
      increased risk of malignancy in future if polyps continue to recur.

PMID- 9564577
TI  - Renal colic as the presenting sign of Cushing syndrome: a case report.

PMID- 9564563
TI  - Natural pathogens of laboratory mice, rats, and rabbits and their effects on
      research.
AB  - Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial,
      parasitic, and fungal agents. Frequently, these organisms cause no overt signs of
      disease. However, many of the natural pathogens of these laboratory animals may
      alter host physiology, rendering the host unsuitable for many experimental uses.
      While the number and prevalence of these pathogens have declined considerably,
      many still turn up in laboratory animals and represent unwanted variables in
      research. Investigators using mice, rats, and rabbits in biomedical
      experimentation should be aware of the profound effects that many of these agents
      can have on research.

PMID- 9564578
TI  - Myringitis bullosa.

PMID- 9564579
TI  - Torture versus child abuse: what's the difference?

PMID- 9564581
TI  - Obstacles to addressing professional misconduct.
AB  - The Ethical Principles exhort psychologists "to encourage ethical behavior by
      students, supervisees, employees, and colleagues, as appropriate" (American
      Psychological Association, 1992, p. 1599). In spite of a clear directive to
      attempt resolution of unethical conduct by colleagues, research indicates that
      satisfactory resolution or actual reporting of misconduct is infrequent. This
      paper will address some of the forces that discourage psychologists from dealing
      responsibly and appropriately with professional misconduct by colleagues. The
      goals of this paper are to promote understanding of factors that interfere with
      the effective resolution of ethical misconduct, to identify possible signs of
      reluctance to address misconduct, and to propose strategies to combat those
      forces that keep us in silent collusion with colleagues who engage in unethical
      practices. A flowchart of steps for addressing possible misconduct by a colleague
      is provided, and educational, organizational, and professional considerations are
      discussed.

PMID- 9564580
TI  - Identity confusion, bisexuality, and flight from the mother.
AB  - This paper deals with the effects of an oral-sadistic annihilating mother on her
      male and female offspring. The all-powerful nature of these mothers, and the
      corresponding helplessness of the fathers, produce in their offspring a sense of
      identity confusion, a struggle with their bisexuality, and a need to distance
      themselves from their mother. Everything unwanted in the mother is externalized
      onto and into the child, particularly suffering and pain, which are necessary for
      the maintenance of the (pathological) mother-child relationship. Positive
      movement (i.e., success) on the child's part threatens the balance of this
      relationship, is perceived by the child as a hostile and destructive triumph over
      the mother, and causes the Negative Therapeutic Reaction in therapy. The child's
      inherent masochism acts to preserve the early infantile omnipotence and leads to
      his/her assumption of all responsibility for the mother's affective states. The
      child's self-destructiveness also functions as a release for unconscious
      aggression toward the mother, due to the lack of boundary differentiation between
      the two.

PMID- 9564582
TI  - Racial differences in combat-related PTSD: empirical findings and conceptual
      issues.
AB  - We critically review the empirical literature on racial differences in
      epidemiology, psychopathology, and treatment outcome in combat veterans with
      posttraumatic stress disorder (PTSD). Although there is a body of literature
      pertaining to various aspects of race and combat-related PTSD, much of the
      writing is conceptual in nature and based on single case or anecdotal reports,
      and there is a striking paucity of rigorous empirical findings. Furthermore,
      despite the prevailing zeitgeist and clinical lore, the limited extant empirical
      evidence suggests that veterans of different races are more similar to each other
      than they are different when it comes to the clinical manifestation and response
      to treatment of combat-related PTSD and associated features. The one area where
      clear differences exist is in epidemiological rates of PTSD, where minority
      combat veterans (i.e., Blacks and Hispanics) have been shown to have higher
      absolute rates of the disorder. However, secondary analyses within the existing
      epidemiological studies suggest that differential rates of PTSD between racial
      groups may be a function of differential rates of traumatic stressors and other
      pre-existing conditions. This finding, in combination with the general paucity of
      empirical data and certain methodological limitations, significantly moderates
      the conclusions that should be reached from this body of literature. Further
      research is needed before we can consider our knowledge in this area complete. A
      number of conceptual and methodological issues are discussed in order to
      highlight future research directions.

PMID- 9564583
TI  - Cognitive behavioural therapy and pharmacotherapy: complementary or contradictory
      approaches to the treatment of anxiety?
AB  - Considerable controversy exists regarding the practice of combining Cognitive
      Behavioural Therapy (CBT) with Pharmacotherapy (PT) in the management of anxiety.
      This paper considers whether these two forms of treating anxiety disorders can be
      effectively combined to enhance treatment outcome. Despite the theoretical appeal
      of a combined approach, a critical review of treatment outcome findings across
      CBT and various anxiolytic medications and their combination, suggests a failure
      of these treatments to operate in a complementary fashion. A detrimental impact
      of anxiolytic medication on CBT outcome is particularly salient for high potency
      benzodiazepines. Low potency benzodiazepines and antidepressants generally have a
      negligible impact with no clear evidence of treatment enhancement and some
      negative combined treatment effects on medication withdrawal and at long-term
      follow-up. Thus, we address potential mechanisms that may explain this treatment
      noncomplementarity and in some cases, treatment incompatibility. Cognitive
      factors influencing treatment outcome (catastrophic beliefs, self-efficacy,
      selective attention, and memory) are highlighted in view of the empirically
      supported mediating role of these variables in accounting for treatment
      responsiveness. Potential effects of anxiolytic medication on cognitive change in
      CBT are postulated. A number of suggestions for future research and clinical
      practice are proposed on the basis of this review.

PMID- 9564584
TI  - Catastrophic cognitions in panic disorder with and without agoraphobia.
AB  - The cognitive models of panic disorder with (PDA) or without (PD) agoraphobia are
      now widely recognised. These models propose that patients misinterpret external
      or internal cues in a catastrophic manner and as a result of these catastrophic
      cognitions the symptoms are maintained. There is now a large body of empirical
      evidence for this proposal and the aim of this paper is to systematically review
      the literature to evaluate whether the empirical evidence supports the
      contribution of catastrophic cognitions to PD and PDA. Empirical studies using
      different methodologies, such as interview, questionnaire, self-monitoring, and
      in vivo techniques are reviewed. The results indicate there is substantial
      empirical evidence in support of the central role of catastrophic cognition in
      cognitive models. Different methodologies provided convergent support for the
      importance of catastrophic cognitions in the maintenance of panic disorder and
      agoraphobia. Limitations in the interpretation of the existing research are
      highlighted and future research directions are proposed.

PMID- 9564585
TI  - Sexual addiction: many conceptions, minimal data.
AB  - Sexual addiction has received increasing attention in the past decade. We review
      existing literature on (a) competing conceptualizations of this syndrome as
      constituting an addictive, obsessive-compulsive, or impulse control disorder; (b)
      symptomatology and progression; (c) etiological models; and (d) treatment
      approaches. Based on this review, we conclude by identifying questions requiring
      resolution via empirical investigation.

PMID- 9564586
TI  - Melanoma.

PMID- 9564587
TI  - Cement injuries. Part III: Cement burns in soccer and rugby players.

PMID- 9564588
TI  - Aural vignettes of dermatologic history. Interview by Victor H. Witten.

PMID- 9564589
TI  - What's eating you? Wheel bug (Reduviidae: Arilus cristatus).

PMID- 9564590
TI  - Epidermal necrosis as a predictive sign of malignancy in adult dermatomyositis.

PMID- 9564591
TI  - Zinc deficiency in exclusively breast-fed infants.
AB  - Zinc deficiency in breast-fed infants is an important disorder. Unlike
      acrodermatitis enteropathica, it is transient and stops when nursing ends. We
      report two cases of premature infants, breast-fed only, who showed skin lesions
      resembling acrodermatitis enteropathica. Results of laboratory investigations
      revealed a lowered zinc level in the infants' serum and in the mothers' milk and
      a normal level of zinc in the mothers' serum. After the infants were given zinc
      supplements and their diets diversified, the skin lesions regressed and their
      serum zinc levels became normal.

PMID- 9564592
TI  - Subcorneal pustular dermatosis: a clinical study of ten patients.
AB  - Subcorneal pustular dermatosis of Sneddon and Wilkinson (SPD) is a unique
      clinical and histologic entity. This disorder has been reported in association
      with monoclonal gammopathy and IgA pemphigus. We report ten additional cases of
      SPD and determine the frequency of monoclonal gammopathy and IgA pemphigus in
      patients with SPD and investigate the relationship of this entity with other
      dermatoses characterized histologically by a subcorneal pustule. The medical
      records of patients with SPD evaluated at the authors' institution from 1980
      through 1995 were reviewed retrospectively. Medical records of twenty patients
      with pustular psoriasis were reviewed for comparison. Ten patients met the
      criteria for SPD. Their average age at diagnosis was 66 years. The characteristic
      flaccid pustules were often generalized and had a tendency to involve the
      flexural areas. Serum monoclonal gammopathy was present in four patients: three
      with IgA and one with IgG. On direct immunofluorescence examination, three
      patients had IgA deposits in the intercellular spaces. None of the patients
      exhibited both monoclonal gammopathy and IgA deposits. Repeated direct
      immunofluorescence studies were necessary to detect IgA pemphigus in one patient.
      SPD is a distinct clinical entity. The findings of IgA deposits intercellularly
      on immunofluorescence and monoclonal gammopathy may help to further identify this
      entity.

PMID- 9564593
TI  - Emergency department management of sunburn reactions.
AB  - The medical records of fifteen patients presenting to the emergency department of
      a university hospital for sunburn were reviewed. Patients with sunburn had a mean
      age of 27 years and injury was most likely to occur in July. Six patients had
      blisters secondary to the ultraviolet injury. Treatment with nonsteroidal anti
      inflammatory drugs was used for nine of fifteen patients. Although eight
      instances of patient education about the primary prevention of future sunburn
      were documented in the medical records, only one patient record had documentation
      of her being warned about her increased risk for skin cancer.

PMID- 9564594
TI  - Solid facial edema as a complication of acne vulgaris.
AB  - A case of persistent solid facial edema in an 18-year-old man from India with
      papulopustular acne vulgaris is reported. Acne lesions responded well to systemic
      antibiotic and topical antiacne treatment, whereas there was a moderate reduction
      in the facial edema with a course of systemic steroid therapy.

PMID- 9564595
TI  - Routine histologic examination for the diagnosis of onychomycosis: an evaluation
      of sensitivity and specificity.
AB  - Clinical differentiation of dermatophyte infection from dystrophic changes due to
      psoriasis may be challenging. Typically, potassium hydroxide (KOH) preparations,
      fungal culture, and occasionally, nail unit biopsy specimens are utilized to help
      differentiate between the two. These tests are often time-consuming and may yield
      false-negative results. Increasing regulation of the office laboratory has caused
      some physicians to forgo this testing, which was previously routine. We
      investigated the utility of routine histologic examination of nail clippings in
      differentiating onychomycosis from psoriatic onychodystrophy. Twenty-three distal
      nail clipping specimens (twelve specimens from patients with onychodystrophy of
      unknown cause and eleven control specimens from nails with known cause) were
      evaluated by routine histology and periodic acid-Schiff (PAS) staining. Of the
      dystrophic cases, four were demonstrated to be onychomycosis by the presence of
      hyphae on histologic evaluation and by culture, whereas only three of these cases
      yielded positive results on KOH examination. Eight cases of onychodystrophy were
      due to psoriasis. Yeast forms were detected on one case of psoriatic
      onychodystrophy that demonstrated yeast growth on culture. In our study, routine
      histologic examination with PAS staining was equal to culture and superior to KOH
      preparation in leading to the correct diagnosis of dermatophyte infection. In
      addition, the diagnosis of psoriasis of the nail plate was detected accurately by
      routine histologic examination. Routine histologic examination with PAS staining
      is a rapid, simple, and reliable test in the evaluation of onychodystrophy.

PMID- 9564596
TI  - Bandlike melasma mimicking linear morphea ("en coup de sabre" type).
AB  - A case of bandlike melasma on the median line of the forehead of a middle-aged
      woman is described. It was an atypical case for its clinical shape and
      distribution. At initial examination, it was diagnosed as linear morphea.
      Epidermal nevus was another differential diagnosis. Based on the presence of
      minor protuberance and the absence of atrophy, clinically, and the presence of
      sebaceous glands and the absence of swelling of collagen fibers, documented
      histologically, we revised our diagnosis to that of an atypical type of melasma.

PMID- 9564597
TI  - Syringoma resembling confluent and reticulated papillomatosis of Gougerot
      Carteaud.
AB  - We report the case of a 31-year-old woman with a rare presentation of syringoma
      resembling confluent and reticulated papillomatosis of Gougerot-Carteaud. The
      lesions have been unresponsive to treatment with topical steroids and retinoic
      acid.

PMID- 9564598
TI  - Cronkhite-Canada syndrome: report of two cases, biopsy findings in the associated
      alopecia, and a new treatment option.
AB  - Two patients with Cronkhite-Canada syndrome (CCS) are reported, both of whom had
      diffuse alopecia, nail and skin changes, gastrointestinal polyposis, diarrhea,
      and wasting. A scalp biopsy was performed in one patient, and the specimen showed
      a marked noninflammatory loss of follicular units, miniaturization of the hair
      shafts, markedly dilated follicles, and a heavy deposition of glycosaminoglycans
      in the reticular dermis. This patient responded to prednisone therapy. The other
      patient was found to have elevated gastric acid levels and responded to
      ranitidine therapy. The conditions of both patients are now in remission two and
      six years later, respectively. Our patients have shown a temporally related
      remission of disease during treatment with prednisone and ranitidine, suggesting
      that each agent may be effective in CCS. However, randomized placebo-controlled
      trials are needed to prove the efficacy of these therapies. Further investigation
      of the histopathologic features of the associated alopecia may determine its
      cause.

PMID- 9564599
TI  - Response of hand dermatitis to a new skin barrier-protectant cream.
AB  - Twenty-five patients with hand dermatitis participated in a pilot study utilizing
      a new skin barrier cream containing white petrolatum. Each patient received
      treatment with SBR-Lipocream, which was applied three to four times daily for a
      period ranging from one to four weeks. All patients completed pre- and postsurvey
      questionnaires and were evaluated by a staff physician prior to, and upon
      completion of, the study. All patients completed the evaluation. Results of the
      survey indicated a general dissatisfaction with currently utilized moisturizers
      and a positive response to the skin barrier cream: 96 percent believed that this
      cream helped their condition. Based on this response, further evaluation of this
      cream's ability to manage this often-chronic condition and prevent exacerbation
      and flares appears warranted.

PMID- 9564600
TI  - Mose Da Prada: development of an outstanding scientist.

PMID- 9564601
TI  - Mose Da Prada and the discovery of tolcapone.

PMID- 9564603
TI  - Monoamine oxidase A deficiency: biogenic amine metabolites in random urine
      samples.
AB  - We have recently described an association between abnormal behaviour and
      monoamine oxidase A (MAO-A) deficiency in several males from a single large Dutch
      kindred. A characteristically abnormal excretion pattern of biogenic amine
      metabolites was present in 24-hour urine of affected males. Because of this
      strikingly abnormal metabolite pattern observed in 24 hour urine samples of MAO-A
      deficient males we hypothesized that it should be possible to diagnose this
      condition by examining random urine samples. We therefore studied multiple urine
      samples obtained over a two-week study period from two males with selective MAO-A
      deficiency. The results demonstrate that the characteristic abnormalities in the
      excretion of biogenic amines and their metabolites were faithfully present in
      every one of 12 independent samples obtained from the MAO-A deficient males over
      the two-week study period. We conclude that MAO-A deficiency can be reliably
      diagnosed by measuring the ratio of normetanephrine (NMN) to VMA (or that of NMN
      to MHPG) in random urine samples.

PMID- 9564602
TI  - Determination of regions important for monoamine oxidase (MAO) A and B substrate
      and inhibitor selectivities.
AB  - MAO-A and -B are defined by their substrate and inhibitor preferences. To
      determine which regions of the isoenzymes confer these preferences, we have
      constructed six chimeric MAO enzymes by reciprocally exchanging corresponding N
      terminal, C-terminal, and internal segments of MAO-A and -B then determined the
      catalytic properties of these chimeric enzymes. N-terminal chimerics A45B and
      B36A were made by exchanging amino acid segments 1-45 and 1-36 of MAO-A and -B
      respectively. C-terminal chimerics A402B and B393A were made by exchanging amino
      acid segments 403-527 and 394-520 of MAO-A and -B respectively, and internal
      chimerics AB161-375A and BA152-366B were made by exchanging amino acid segments
      161-375 and 152-366 of MAO-A and -B respectively. The enzymatic properties
      observed for the chimerics suggest that the exchanged internal regions but not
      the N- or C-terminal regions confer substrate and inhibitor preferences.

PMID- 9564604
TI  - Relationship between monoamine oxidase (MAO) A specific activity and proportion
      of human skin fibroblasts which express the enzyme in culture.
AB  - Total deficiency of monoamine oxidase A (MAO-A) in affected males of a single,
      human kindred appears to be associated with mild mental retardation and
      significant behavioral anomalies. Though total MAO-A deficiency appears to be
      rare, the extent and significance of individual variation in monoamine oxidase A
      activity in human populations is unclear. Since MAO-A activity is undetectable in
      blood cells, most systematic surveys of individual variation MAO-A activity have
      compared enzyme activity in human fibroblasts cultured from skin biopsies.
      Surprisingly, MAO-A activity in skin fibroblast cultures from unrelated donors
      ranges over 100-fold. It has been suggested that this extreme variation in
      fibroblast MAO-A activity between donors reflects individual, genetic variation
      in the regulation of MAO-A in fibroblasts. I have found from studies with
      immunofluorescence microscopy and flow cytometry that the proportion of MAO-A+
      cells in fibroblast cultures is (a) highly variable between cultures, (b) a
      reproducible characteristic of each culture and (c) the primary factor
      responsible for variation in MAO-A specific activity in whole cell, skin
      fibroblast homogenates. It has been shown previously that MAO-A activity of a
      skin fibroblast culture is relatively constant with continued passage prior to
      cellular senescence. Therefore, these new data raise the possibility that MAO-A
      expression is confined to a functionally distinct subset of human skin
      fibroblasts.

PMID- 9564605
TI  - Are MAO-A deficiency states in the general population and in putative high-risk
      populations highly uncommon?
AB  - Lack of monoamine oxidase A (MAO-A) due to either Xp chromosomal deletions or
      alterations in the coding sequence of the gene for this enzyme are associated
      with marked changes in monoamine metabolism and appear to be associated with
      variable cognitive deficits and behavioral changes in humans and in transgenic
      mice. In mice, some of the most marked behavioral changes are ameliorated by
      pharmacologically-induced reductions in serotonin synthesis during early
      development, raising the question of possible therapeutic interventions in humans
      with MAO deficiency states. At the present time, only one multi-generational
      family and a few other individuals with marked MAO-A deficiency states have been
      identified and studied in detail. Although MAO deficiency states associated with
      Xp chromosomal deletions were identified by distinct symptoms (including
      blindness in infancy) produced by the contiguous Norrie disease gene, the
      primarily behavioral phenotype of individuals with the MAO mutation is less
      obvious. This paper reports a sequential research design and preliminary results
      from screening several hundred volunteers in the general population and from
      putative high-risk groups for possible MAO deficiency states. These preliminary
      results suggest that marked MAO deficiency states are very rare.

PMID- 9564606
TI  - Differential trace amine alterations in individuals receiving acetylenic
      inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline).
AB  - Marked, dose-dependent elevations in the urinary excretion of phenylethylamine,
      para-tyramine, and meta-tyramine were observed in depressed patients treated for
      three or more weeks with 10, 30, or 60 mg/day of the partially-selective
      inhibitor of MAO-B, selegiline (l-deprenyl). In comparative studies with other,
      structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A
      inhibitor used in doses of 90 mg/day for three or more weeks, produced elevations
      in these trace amines which were similar to those found with the highest dose of
      selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of
      30 mg/day for three or more weeks (a dose/time regimen previously reported to
      reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4
      hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect
      on MAO-A in humans in vivo) produced negligible changes in trace amine excretion.
      In comparison to recent studies of individuals lacking the genes for MAO-A, MAO
      B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in
      individuals with a mutation affecting only MAO-A is in agreement with the
      observed lack of effect of clorgyline in the present study. Selegiline produced
      larger changes in trace amines--at least at the higher doses studied--than found
      in individuals lacking the gene for MAO-B, in agreement with other data
      suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in
      doses higher than 10 mg/day. Overall, trace amine elevations in individuals
      receiving the highest dose of deprenyl or receiving pargyline were approximately
      three to five-fold lower than the elevations observed in individuals lacking the
      genes for both MAO-A and MAO-B, suggesting that these drug doses yield incomplete
      inhibition of MAO-A and MAO-B.

PMID- 9564608
TI  - Deprenyl monotherapy improves visuo-motor control in early parkinsonism.
AB  - Deprenyl is a potent MAO-B inhibitor which is commonly prescribed for treatment
      of parkinsonism. Despite prevalent use its effects on the symptoms and course of
      Parkinson's disease (PD) are still debated. The present study was therefore
      undertaken in order to measure quantitatively changes in visuo-motor control
      (VMC), consequent to deprenyl monotherapy in early PD. Previous work from our
      laboratory has shown typical VMC deterioration in PD patients, that correlates
      with disease severity. Thus, measurements of such changes provides a sensitive
      tool with which the symptomatic effects of drug treatment can be assessed
      quantitatively. Fourteen newly diagnosed, PD patients with light symptoms were
      studied. The VMC of all patients was tested after the first neurological
      examination, before drug treatment commenced. A second test was done after 30
      days of treatment with deprenyl at a dose of 2.5 mg/day. Following this test,
      dosage was increased to 10 mg/day and a third VMC test was given after 30 more
      days of treatment. Our results show significant improvement in VMC functions
      following 30 days of 2.5 mg/day treatment and a continuing improvement after the
      next 30 days of 10 mg/day treatment. This improvement pertains mainly to
      directional control of self initiated movements and is smaller for movements that
      are guided externally. We conclude that deprenyl monotherapy has a clear
      symptomatic beneficial effect for patients with early PD.

PMID- 9564607
TI  - Experience with tranylcypromine in early Parkinson's disease.
AB  - A leading hypothesis of the pathogenesis of neuronal degeneration of the
      substantia nigra dopamine-containing cells in Parkinson's disease (PD) is
      excessive oxidative stress. In part, this oxidative stress is the result of the
      oxidation of dopamine by the action of monoamine oxidases (MAO) A and B to
      generate hydrogen peroxide and subsequent oxygen free radicals. Because of this
      hypothesis we have treated patients with early PD, not yet requiring any
      symptomatic treatment, with tranylcypromine, a drug that inhibits both MAO's.
      These patients were required to observe a tyramine-restricted diet. Thirty-seven
      patients on tranylcypromine have been followed by us for up to 33 months. Four
      patients discontinued the drug because of pending surgery. Of the remaining 33,
      six had adverse effects that lead to discontinuation of the drug, mainly
      impotency in men. Another common adverse effect encountered was insomnia, but
      this problem was not a cause of stopping the drug. Depression lifted in all five
      patients who had this problem at the time tranylcypromine was initiated. Only two
      patients have so far required treatment with levodopa or a dopamine agonist, and
      this need occurred within the first 6 months of treatment. The evaluation of all
      37 patients revealed that parkinsonian symptoms improved slightly on introduction
      of tranylcypromine as measured by the United Parkinson's Disease Rating Scale,
      the Hoehn & Yahr Staging Scale, and the Schwab & England Activities of Daily
      Living Scale. Follow-up evaluations for a minimum of 6 months between the first
      post-tranylcypromine visit and the most recent visit revealed only slight
      worsening of parkinsonian signs and symptoms, with a mean interval of almost 1.5
      years. A longer period of follow-up is needed to determine how long the severity
      of PD will remain mild in this group of patients.

PMID- 9564609
TI  - Endogenous monoamine oxidase A inhibitory activity (tribulin), measured in
      saliva, is related to cardiovascular reactivity in normal individuals.
AB  - Salivary monoamine oxidase A inhibitory activity (MAO-AI), mean arterial blood
      pressure (MAP) and heart rate (HR) were determined simultaneously in healthy male
      students (n = 13) at rest, before a mild psychological stressor, twice during the
      task and 18 minutes after the end of the task. The sample as a whole showed
      significant differences in MAP and HR across occasions (respectively, p < 0.001
      for both). Salivary MAO-AI could distinguish novice and experienced game players
      (p < 0.02) and was consistently positively correlated with MAP (r = 0.58, p <
      0.05 on occasion 2). Pre-task measures of MAO-AI for an increased sample (n = 18)
      were associated with higher MAP (but not HR) throughout the experiment (p <
      0.05). Those subject with falling MAO-AI profiles from task to recovery showed
      significantly greater simultaneous decline in HR than those with a rising MAO-AI
      profile (p < 0.05).

PMID- 9564610
TI  - MAO inhibitory side effects of neuroleptics and platelet serotonin content in
      schizophrenic patients.
AB  - In order to study the putative monoamine oxidase (MAO) inhibitory side effect of
      neuroleptics and simultaneous changes in platelet serotonin content both MAO-B
      activity and serotonin (5-HT) content in platelets of 30 healthy volunteers and
      50 schizophrenic patients treated with neuroleptics were investigated. Our
      results have shown significantly lower MAO-B activity (15.26 +/- 6.81 S.D. vs.
      8.63 +/- 3.82 mmol/hour/10(9) platelets) and higher platelet 5-HT content (906.19
      +/- 285.33 vs. 1,727.85 +/- 947.40 ng/10(9) platelets) in the schizophrenic
      group. Platelet MAO-B activity was considerably lower in paranoid and residual
      schizophrenics compared with other patients, however, no difference was found in
      platelet 5-HT content between different subtypes of schizophrenia. Various
      neuroleptic treatments did not produce different effects either on platelet
      serotonin content or platelet MAO-B activity.

PMID- 9564611
TI  - Modulation of glutamate neurotoxicity in the transformed cell culture by
      monoamine oxidase inhibitors, clorgyline and deprenyl.
AB  - Addition of 30mM glutamate to the culture medium decreased growth of rat glioma
      C6 cells accompanied by a decrease of DNA synthesis and an increase of lactate
      dehydrogenase (LDH) detected in the conditioned medium. The presence of 1 microM
      deprenyl attenuated the glutamate effect on cell growth only during the first 24
      48 h incubation and had a minor influence on the glutamate-induced decrease of
      DNA synthesis. Clorgyline (1 microM) potentiated glutamate-induced DNA synthesis
      during the first 24 h incubation without significant influence on the cell
      growth. Deprenyl slightly attenuated the glutamate-induced LDH increase during 24
      h incubation but potentiated the glutamate effect at 96 h. Clorgyline decreased
      the glutamate influence at 24 h and especially 96 h. All these effects were
      observed in the absence of exogenous monoamines in the culture medium. These
      results suggest that in transformed cells monoamine oxidase (MAO) inhibitors may
      influence processes of cell death via MAO-independent mechanisms.

PMID- 9564612
TI  - A cell culture model of cerebral ischemia as a convenient system to screen for
      neuroprotective drugs.
AB  - Aggregation cultures of rat brain were exposed to a combination of anoxia and
      hypoglycaemia for 30 minutes. Thereafter, the release of lactate dehydrogenase
      into the cell culture medium was monitored up to 4 days as a measure of cell
      damage after the ischemic insult. Some cultures were treated with different
      concentrations of deprenyl or tolcapone, selective inhibitors of monoamine
      oxidase B and catechol-O-methyltransferase, respectively. After 1 day in culture,
      the release of lactate dehydrogenase was significantly reduced in cultures
      treated with deprenyl (at 1 nM. 100 nM, and 10 microM), as well as in cultures
      treated with 1 nM or 100 nM tolcapone; 10 microM of tolcapone, on the other hand,
      resulted in a toxic effect on the cell aggregates. No differences in the release
      of lactate dehydrogenase into the medium was observed in the aggregates treated
      with drugs as compared with the control cultures after 2 or 4 days post-ischemia.

PMID- 9564613
TI  - Neuroprotection by selegiline and other MAO inhibitors.
AB  - A proposal for the nomination of the father of monoamine oxidase inhibitors is
      presented. A brief history of the human clinical pharmacology of selegiline is
      considered including the results of two major prospective ongoing clinical trials
      and recent evidence on the effects of sustained selegiline therapy on postural
      blood pressures in parkinsonians is discussed.

PMID- 9564614
TI  - The neuroprotective and neuronal rescue effects of (-)-deprenyl.
AB  - The pharmacological effects of (-)-deprenyl is multi-fold in its nature (dopamine
      sparing activity, neuroprotective and neuronal rescue effects), which cannot be
      explained solely by the irreversible MAO-B inhibitory action of the substance.
      Deprenyl slightly inhibits the re-uptake of noradrenaline and dopamine, but
      methylamphetamine, the metabolite of the inhibitor, by one order of magnitude is
      more potent in this respect, than the parent compound. Neither the metabolite nor
      (-)-deprenyl acts on the uptake of serotonin. The inhibitor has an intensive
      first pass metabolism after oral treatment. The in vivo pharmacokinetic studies
      with (-)-deprenyl, using the double labelled radioisotope technique (1.5 mg/kg;
      orally) in rats revealed that the molar concentration of methylamphetamine can
      reach the level suitable to induce a significant inhibition of amine uptake.
      Deprenyl, but especially methylamphetamine pre-treatment can prevent the
      noradrenaline release induced by the noradrenergic neurotoxin DSP-4. The uptake
      inhibitory effect of (-)-deprenyl and the metabolites is reversible. After
      repeated administration of (-)-deprenyl (1.5 mg/kg daily, for 8 days) sustained
      concentration of its metabolites was detected, compared to that of the acute
      studies. This can at least partly explain why (-)deprenyl should be administered
      daily to evoke therapeutic effects in Parkinson's disease. Administration of (-)
      deprenyl in a low dose, following the toxic insult, can rescue the damaged
      neurones. The neuronal rescue effect of the drug was studied on M-1 human
      melanoma cells in tissue culture. The inhibitor reduced the apoptosis of serum
      deprived M-1 cells, but the (+)-isomer failed to exert this effect. The (+/-)
      desmethyl-deprenyl almost lacks the property to inhibit apoptosis. For
      neuroprotection and neuronal rescue an optimal dose of (-)-deprenyl should be
      administered, because to reach a well balanced concentration of the metabolites
      in tissues is critical.

PMID- 9564615
TI  - Oxidation of N-methyl(R)salsolinol: involvement to neurotoxicity and
      neuroprotection by endogenous catechol isoquinolines.
AB  - 1(R), 2(N)-Dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N
      methyl(R)salsolinol, is a potent dopaminergic neurotoxin to induce parkinsonism
      in rats. The cytotoxicity of N-methyl(R)salsolinol proved to be ascribed to its
      oxidation into cytotoxic 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion with
      generation of hydroxyl radical. The isoquinolinium ion caused massive necrosis in
      the striatum, whereas N-methyl(R)salsolinol depleted selectively dopaminergic
      neurons in the substantia nigra without necrotic tissue reaction. N
      Methyl(R)salsolinol induced DNA damage to human neuroblastoma SH-SY5Y cells,
      which could be prevented by anti-oxidants and cycloheximide. These results
      suggest that oxidative stress through oxidation of N-methyl(R)salsolinol induces
      apoptotic cell death. On the other hand, (R)salsolinol proved to scavenge
      hydroxyl radical produced by oxidation of dopamine. The neurotoxicity and
      neuroprotection of catechol isoquinolines may be ascribed to their oxidation and
      scavenging of radicals.

PMID- 9564616
TI  - Substrate regulation of monoamine oxidases.
AB  - The rate of oxidation by monoamine oxidase (MAO) of a particular amine in a given
      cell depends on the levels of MAO-A and MAO-B expressed in the mitochondrial
      outer membranes, on the amine concentration and the oxygen concentration. Its
      disposal will be slowed by the presence of competing amines or endogenous
      inhibitors. However, substrate binding alters the properties of MAO and
      influences catalytic turnover. (a) It increases the redox potential of the flavin
      making possible the transfer of electrons from the higher potential amine. (b) It
      accelerates the reactivity of the covalently bound flavin with oxygen,
      effectively increasing the Vm (particularly for MAO-B). (c) It bypasses the
      generation of free oxidised enzyme in the reaction cycle so that, at high amine
      concentrations, only the affinity of a substrate or inhibitor for the reduced
      enzyme (particularly for MAO-A) is important. These changes are induced only by
      substrate, not by the few stable products available nor by inhibitors suggesting
      a very specific interaction between a substrate ligand and the enzyme. The
      altered properties are very different for MAO-A and MAO-B even with the same
      substrate. Elucidation of the mechanisms involved must await structural
      information from physical studies, molecular modelling and mutational analysis.

PMID- 9564617
TI  - Monoamine oxidases and related amine oxidases as phase I enzymes in the
      metabolism of xenobiotics.
AB  - To date most of the interest in oxidative metabolism of xenobiotics has been
      devoted to the role of the microsomal cytochrome P-450 system and to establish
      the basis for classifying and naming P450 enzymes. The contribution of amine
      oxidases to the metabolism of xenobiotics has been largely neglected, with the
      exception of the contribution of monoamine oxidases (MAOs) to the metabolism of
      exogenous tyramine and the studies of the "cheese effect" produced as the result
      of ingestion of large amounts of tyramine-containing foods under particular
      conditions. A review of the involvement of the mitochondrial MAOs in drug
      metabolism was published in 1988. Since that time, considerable additional
      evidence has appeared in the literature to support the contribution of MAOs to
      drug metabolism. In addition, the involvement of other amine oxidases in the
      metabolism of foreign compounds has been established. A second review on the
      contribution of amine oxidases to the metabolism of xenobiotics was therefore
      published in 1994. On an arbitrary basis, the heterogeneous class of amine
      oxidases can be divided into two types according to their prosthetic group: the
      flavineadenine dinucleotide (FAD)-dependent amine oxidases (Monoamine Oxidase and
      Polyamine Oxidase) and the amine oxidases not containing FAD (Semicarbazide
      sensitive amine oxidases). In this overview, the contributions of these two types
      in xenobiotic metabolism are considered separately.

PMID- 9564618
TI  - Monoamine oxidases: from brain maps to physiology and transgenics to
      pathophysiology.
AB  - The present report reviews recent advances in mapping the cellular sites of
      synthesis and catalytic activity, as well as age- and disease-related changes of
      monoamine oxidases A and B in the brain. A transgenic model of oxidative stress
      is also described. The relevance of these findings for the physiological and
      pathophysiological roles of monoamine oxidases is briefly discussed.

PMID- 9564619
TI  - Structure-function relationships of mitochondrial monoamine oxidase A and B:
      chimaeric enzymes and site-directed mutagenesis studies.
AB  - To gain insight into the structure of monoamine oxidases (MAO) A and B, we
      investigated the properties of various chimaeric enzymes, engineered by moving
      progressively the junction between the NH2- and the COOH-termini of each MAO
      form. Whereas exchange of the ADP-binding sequence did not modify the catalytic
      properties of either MAO isoforms, chimaeras with increasing length of the NH2
      terminus of MAO-A (up to position 256) showed a marked decrease in affinity
      towards substrates and inhibitors. Two sequences, spanning position 62 to 103 and
      146 to 220, appeared of particular importance in putatively constituting the
      binding site of MAO-B. Conversely, the catalytic properties and specificity of
      MAO-A were insensitive to substitution of both the NH2-(up to position 112) and
      COOH-termini (from residue 395), but further modification of the central sequence
      of MAO-A was not compatible with activity. None of the engineered chimaeras
      showed a shift in substrate and inhibitor specificity. Investigation on MAO-B by
      site-directed mutagenesis revealed that His382 and Thr158 may represent residues
      relevant for MAO-B catalytic mechanism.

PMID- 9564620
TI  - Deamination of methylamine and angiopathy; toxicity of formaldehyde, oxidative
      stress and relevance to protein glycoxidation in diabetes.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is located in the vascular smooth
      muscles, retina, kidney and the cartilage tissues, and it circulates in the
      blood. The enzyme activity has been found to be significantly increased in blood
      and tissues in diabetic patients and animals. Methylamine and aminoacetone are
      endogenous substrates for SSAO. The deaminated products are formaldehyde and
      methylglyoxal respectively, as well as H2O2 and ammonia, which are all
      potentially cytotoxic. Formaldehyde and methylglyoxal are cytotoxic towards
      endothelial cells. Excessive SSAO-mediated deamination may directly initiate
      endothelial injury and plaque formation, increase oxidative stress, which can
      potentiate oxidative glycation, and/or LDL oxidation and damage vascular systems.
      Formaldehyde is also capable of exacerbating advanced glycation, and thus
      increase the complexity of protein cross-linking. Uncontrolled SSAO-mediated
      deamination may be involved in the acceleration of the clinical complications in
      diabetes.

PMID- 9564622
TI  - The oxidation of dopamine and epinine by the two forms of monoamine oxidase from
      rat liver.
AB  - Information on the "in vitro" oxidation of epinine by monoamine oxidase (MAO)
      compared to dopamine is very poor. The aim of this work was to study the
      oxidative deamination of epinine and dopamine by rat liver MAO-A and MAO-B. The
      contributions of MAO-A and B to the metabolism of dopamine (55% and 45%,
      respectively) and epinine (70% and 30%, respectively) were similar. The results
      of this study show that epinine is a substrate for both forms of MAO in rat
      liver, although the contribution of MAO A to the deamination of this secondary
      amine appears to be slightly more important than that of MAO B.

PMID- 9564621
TI  - Monoamine oxidase activities in human cystic and colonic arteries--influence of
      age.
AB  - The deamination of 5-hydroxytryptamine, phenylethylamine and benzylamine by
      monoamine oxidases (MAO-A and B) and semicarbazide sensitive amine oxidase (SSAO)
      respectively has been studied in homogenates of human cystic and colonic arteries
      by radiochemical assays. In cystic artery the deamination is mainly carried out
      by SSAO with a lower participation of MAO-B. The kinetic parameters were: to MAO
      B the Vmax = 15.11 +/- 0.51 nmol/mg protein.h and the Km = 78.51 +/- 5.16 microM
      (+/- SE) and to SSAO the Vmax = 211.70 +/- 8.75 nmol/mg protein.h and the Km =
      211.51 +/- 23.27 microM (+/- SE). We could not measure MAO-A activity in our
      experimental conditions and also the levels of catecholamines are very low and
      the histological studies show a poor innervation in these tissues. In colonic
      artery the kinetic parameters were: to MAO-B the Vmax = 5.09 +/- 0.31 nmol/mg
      protein.h and the Km = 29.12 +/- 4.55 microM (+/- SE) and to SSAO the Vmax =
      273.67 +/- 8.35 nmol/mg protein.h and the Km = 197.89 +/- 21.81 microM (+/- SE).
      In this artery we could find MAO-A in five among the nine samples studied and the
      kinetic parameters were: the Vmax = 14.48 +/- 0.82 nmol/mg protein.h and the Km =
      136.40 +/- 25.46 microM. As we have performed the experiments with human vessels
      from donors with different age we could not find any relationship between the
      activity or affinity, in MAO-B and SSAO, with age. Nevertheless, the results show
      in cystic artery an increase in the affinity of MAO-B with age when we consider
      the female group which suggests a possible role of the hormonal condition in this
      behaviour.

PMID- 9564623
TI  - Properties and functions of tissue-bound semicarbazide-sensitive amine oxidases
      in isolated cell preparations and cell cultures.
AB  - The demonstration of semicarbazide-sensitive amine oxidase (SSAO) activity in
      some freshly-dispersed cell preparations and in particular types of cells grown
      in culture, provides increasing opportunities for investigating the importance of
      SSAO in various aspects of cellular function. Assays of benzylamine and
      methylamine metabolism in homogenates of cultured cells have established clearly
      that SSAO is expressed in rat and pig vascular (aortic) smooth muscle cells, as
      well as in rat non-vascular (anococcygeus, trachea) smooth muscle, brown and
      white adipocytes. However, to date little or no SSAO activity has been detected
      in cultures of human vascular smooth muscle cells grown from blood vessels (e.g.
      umbilical artery) known to contain the enzyme, and the reason for this is not yet
      apparent. However, those cell cultures expressing SSAO are offering useful
      experimental models for studying biochemical and toxicological consequences upon
      cellular function which may result from the metabolism of various aromatic and
      aliphatic amines suggested to be possible physiological and xenobiotic substrates
      of the enzyme.

PMID- 9564624
TI  - Studies on the time-dependent activation of microsomal semicarbazide-sensitive
      amine oxidase.
AB  - The semicarbazide-sensitive amine oxidase (SSAO) from bovine lung microsomes was
      activated in a temperature- and time-dependent process. This behaviour was
      observed when the enzyme was preincubated at 25 degrees C, 37 degrees C and 50
      degrees C but not at 4 degrees C. This activation was only observed when
      benzylamine was used as substrate but not when methylamine, histamine or 2
      phenylethylamine were used. The activation was independent of pH, ionic strength
      and the nature of the buffer used. At 37 degrees C the specific activity had
      risen to a value that was about 7 times higher than that of the starting material
      after 120 min. This process affected only the maximum velocity of the reaction
      with the Km value remaining essentially unchanged. Treatment of SSAO with
      phospholipases and detergents did not affect this behaviour. Incubation of the
      enzyme with serine proteases, metal chelating agents, reducing agents or protease
      inhibitors, had no effect on the activation. The fact that both forms of the
      enzyme (activated and non-activated), showed the same Mr values on gel filtration
      chromatography excluded the possibility of an enzyme aggregation and/or
      degradation being involved in this process.

PMID- 9564625
TI  - Studies on the behaviour of semicarbazide-sensitive amine oxidase in Sprague
      Dawley rats treated with the monoamine oxidase inhibitor tranylcypromine.
AB  - The possibility that increased levels of the activity of the semicarbazide
      sensitive amine oxidase (SSAO) might, to some extent, compensate for the loss of
      monoamine oxidase (MAO) activity in the atypical form of Norrie Disease, was
      examined using the rat as a model. Long-term treatment with the MAO inhibitor
      tranylcypromine (1 mg/kg/day) resulted in sustained inhibition of MAO-A and MAO-B
      activities in liver and brain. After one week, the SSAO activity in heart had
      increased by 79% above the control levels. This increase was maintained for 3
      weeks. Since such alterations might result from enzyme induction, the turnover of
      the enzyme was studied in cultured cells from rat aortic smooth muscle. The time
      course of recovery of enzyme activity following irreversible inhibition by MDL
      72145 corresponded to a half-life of approximately 6 days for this process.

PMID- 9564626
TI  - Semicarbazide-sensitive amine oxidase in pig heart.
AB  - A semicarbazide-sensitive amine oxidase (SSAO) (E.C.1.4.3.6) has been purified
      from pig heart. Western blot analysis showed that the enzyme reacts with a
      polyclonal antibody raised against homogeneous crystalline pig plasma benzylamine
      oxidase (BAO). A subunit molecular mass of 97 KDa obtained by SDS electrophoresis
      is identical to the plasma enzyme. The purification procedure consisted of
      sequential DEAE cellulose, octyl-Sepharose, Con A-Sepharose and hydroxyapatite
      columns. Two peaks of activity were obtained on octyl-Sepharose which were found
      to be kinetically and immunologically indistinguishable. The specific activity of
      the purified enzyme was 0.045 mumol/min/mg of protein at 37 degrees C and the Km
      for benzylamine was estimated to be 63 microM. The enzyme was inhibited by
      carbonyl reagents such as semicarbazide but was insensitive to the effect of
      pargyline.

PMID- 9564627
TI  - Chronic TVP-1012 (rasagiline) dose--activity response of monoamine oxidases A and
      B in the brain of the common marmoset.
AB  - The stereospecific form of the known acetylenic mechanism-based MAO-inhibitor
      AGN1135 (Rasagiline, TVP-1012) is devoid of sympathomimetic amphetamine-like
      properties. To evaluate the efficiency and selectivity of subcutaneous injections
      of TVP-1012 (dose range from 0.01 up to 10 mg/kg for 7 days) the activities of
      monoamine oxidases A and B (MAO-A,-B) were determined in different brain regions
      of the common marmoset. At a dose of 0.1 mg/kg TVP-1012, almost 80% of MAO-B
      activity is inhibited in all brain regions investigated (prefrontal and occipital
      cortex, cerebellum, caudate nucleus, putamen, nucleus accumbens). In contrast,
      MAO-A is not inhibited in putamen and nucleus accumbens. However, by increasing
      the TVP-1012 dose to 0.5 mg/kg, MAO-A is inhibited to a significant extent as
      well, concomitant to total inhibition of MAO-B. The results obtained indicate
      that TVP-1012 irreversibly inhibits both types of MAO in the common marmoset with
      selectivity for MAO-B at doses less than 0.5 mg/kg. TVP-1012 could be useful in
      studies requiring selective MAO-B inhibition without concomitant sympathomimetic
      amphetamine-like effects and could thus be of therapeutic interest for
      Parkinson's disease and retarded depression.

PMID- 9564628
TI  - Increased striatal dopamine production from L-DOPA following selective inhibition
      of monoamine oxidase B by R(+)-N-propargyl-1-aminoindan (rasagiline) in the
      monkey.
AB  - Striatal extracellular fluid concentrations of dopamine and metabolites in
      response to direct striatal administration of two L-DOPA boluses administered
      sequentially were determined in three rhesus monkeys during halothane anesthesia.
      Whereas in an initial microdialysis run, generation of dopamine was less
      following the second L-DOPA bolus than the first, in a subsequent run, in which
      the selective MAO-B inhibitor R(+)-N-propargyl-1-aminoindan (rasagiline) was
      administered systemically (0.2 mg/kg s.c.) between the two L-DOPA boluses,
      generation of dopamine was greater following the second bolus.

PMID- 9564629
TI  - Effects of N-propargyl-1-(R)aminoindan (rasagiline) in models of motor and
      cognition disorders.
AB  - N-propargyl-1-(R)aminoindan (rasagiline) is a new and selective irreversible MAO
      B inhibitor, currently being considered as the mesylate salt for potential
      therapy in certain neurological disorders. It has been studied in animal models
      of cognition and motor dysfunction. Its ability to restore normal motor activity
      was determined in models of acute drug-induced dopaminergic dysfunction: Its
      effects in improving cognition and memory deficits was studied in adult and
      senescent rats that had been exposed to prolonged hypoxia, then subjected to the
      passive and active avoidance tests. In alpha-methyl-p-tyrosine (alpha-MpT)
      induced hypokinesia (100-120 mg/kg, i.p.) pretreatment with rasagiline at 2.5
      mg/kg i.p. restored motor activity to control level. But pretreatment with
      reserpine abolished the protective effect of rasagiline. Rasagiline at 0.5
      mg/kg/day was protective against alpha-MpT also in hypoxia-lesioned rats. In
      haloperidol-induced catalepsy in rats (1.5 mg/kg, s.c.) or mice (4-6 mg/kg s.c.),
      rasagiline improved recovery of normal locomotion, gait and coordination at 0.4
      2.4 mg/kg i.p. and 1.8-1.5 mg/kg i.p., respectively. In amphetamine-induced
      stereotypy (0.6 mg/kg s.c., rasagiline potentiated this effect at 1.5 mg/kg i.p.
      In hypoxia-induced impairment of memory and learning, rasagiline at 0.32-0.5
      mg/kg/day per os improved performance of adult rats in passive and active
      avoidance, and of senescent rats in active avoidance. Selegiline was either
      ineffective or less effective at equivalent doses. Racemic N-propargyl-1
      aminoindan (AGN-1135), besides being of lower potency, had a different dose
      dependency than rasagiline in antagonizing haloperidol-induced catalepsy or alpha
      MpT-induced hypokinesia. 1-(R)aminoindan ((R)AI), a metabolite of rasagiline, in
      relatively high doses produced effects that were distinct in certain respects
      from those of rasagiline.

PMID- 9564630
TI  - (R)(+)-N-propargyl-1-aminoindan (rasagiline) and derivatives: highly selective
      and potent inhibitors of monoamine oxidase B.
AB  - (+)-N-Propargyl-1-aminoindan (rasagiline) and a series of derivatives have been
      synthesized and screened for monoamine oxidase inhibitory activity. Rasagiline
      and several analogues were found be highly selective and potent inhibitors of the
      B form of the enzyme in contrast to the levorotatory enantiomer which was not
      active. The results indicate that rasagiline has potential for the treatment of
      Parkinson's Disease. This compound is currently under development for that
      indication.

PMID- 9564632
TI  - Long-term administration of (-)-deprenyl increases mortality in male Wistar rats.
AB  - Long-term administration of the monoamine oxidase inhibitor (-)-deprenyl (0.5
      mg/Kg) for up to 20 months significantly increased mortality in the male Wistar
      rat, whereas the dopamine agonist pergolide (0.4 mg/Kg) and the antioxidant
      diethyldithiocarbamate (400 mg/Kg) had no significant effect on mortality. The
      increased mortality was not related to dietary intake or body weight of the rats.
      This is of interest in the light of recent evidence that (-)-deprenyl increases
      mortality in humans.

PMID- 9564631
TI  - Function of endogenous monoamine oxidase inhibitors (tribulin).
AB  - Recent research on tribulin [low molecular weight endogenous inhibitory activity
      of monoamine oxidase (MAO)] has confirmed that its level is increased in both
      human urine and rat tissues by stress or anxiety, and by anxiogenic drugs.
      However tribulin is now known to contain several different molecules. The raised
      inhibitory activity in rat tissues is selective for MAO-A. There is a parallel
      decrease in MAO-A activity ex vivo, suggesting a possible functional effect.
      Increase in endogenous MAO I may competitively inhibit the binding of
      irreversible MAO I drugs, and may also help to mediate some mood altering effects
      of other drugs, or procedures such as ECT. In human urine both MAO-A I and MAO-B
      I have been found to be increased in mild stress. Similar findings have been made
      with human saliva. Selective inhibitors of MAO-A have been identified from human
      urine, and pig brain, but it is not yet clear to what extent they account for the
      MAO-A I activity increased in stress. Isatin is an endogenous selective inhibitor
      of MAO-B (K1 approximately 3 microM). It has a distinct distribution in rat
      brain, with highest concentration in the hippocampus of 0.1 microgram/g. Its
      level is increased by pentylene tetrazole, and isatin is itself anxiogenic in
      rodent models. Its administration also increases monoamine levels in the brain.
      It is a potent antagonist of the ANP receptor, and it may act to link the control
      of monoamine function and natriuresis.

PMID- 9564633
TI  - Selegiline as immunostimulant--a novel mechanism of action?
AB  - In clinical studies the MAO-B inhibitor selegiline appears to slow the
      progression of neurological deficits in Parkinson's disease (PD) and the
      cognitive decline in Alzheimer's disease (AD). The mechanisms of action remain
      unclear. Several lines of evidence indicate an immune-mediated pathophysiology of
      PD and AD. According to animal trials, selegiline increases the survival rate of
      immune suppressed mice. Stimulation of the immune response to bacterial or viral
      infection or in chronic inflammatory processes in managed by an increased
      synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequent
      interleukin-6 (IL-6). Outcome of viral or bacterial infections in the brain
      highly correlates with levels of the cytotoxic cytokine tumor-necrosis-factor
      alpha (TNF). The aim of our study was to characterize the influence of selegiline
      on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood
      mononuclear cells (PBMC) from healthy blood donors. After isolation and washing
      PBMC were cultured without and with selegiline in three different concentrations
      (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified atmosphere (7%
      CO2). Then cultures were centrifuged and supernatants were collected for IL-1
      beta, IL-6 and TNF ELISA-assays. Treatment of cultured PBMC with various
      concentrations induced an increased synthesis of IL-1 beta (ANOVA F = 9.703, p =
      0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a reduced production of TNF
      (ANOVA F = 3.770, p = 0.040). These results indicate, that the influence of
      selegiline on the cytokine biosynthesis may also contribute to its putative
      neuroprotective properties.

PMID- 9564634
TI  - Clorgyline effect on pineal melatonin biosynthesis in rats with lesioned
      suprachiasmatic nuclei.
AB  - We have reported that clorgyline-induced stimulation of pineal melatonin
      biosynthesis could be augmented by the exposure to 24h of constant light in young
      but not in aged rats. Aging is associated with the declined integrity of the
      suprachiasmatic nuclei (SCN), the major station of the light signal passage from
      the retina to the pineal gland. The present study aimed to investigate whether
      SCN integrity is essential for clorgyline effects on pineal melatonin
      biosynthesis in light-primed rats. Clorgyline (2.5 mg/kg, s.c.) was administered
      to sham-operated and SCN-lesioned Sprague-Dawley rats kept under regular
      light/dark cycle or exposed to 24h of constant light. Pineal melatonin and
      related indoles were evaluated by HPLC-fluorimetric procedure. Clorgyline
      stimulated pineal melatonin biosynthesis in both SCN-lesioned and sham-operated
      rats kept under regular light/dark cycle. Exposure to constant light (for 24h)
      augmented clorgyline-induced stimulation of melatonin biosynthesis in sham
      operated rats, but not in SCN-lesioned animals. The obtained results suggest that
      decline in SCN activity (e.g., age-associated) might contribute to previously
      reported attenuation of clorgyline-induced stimulation of melatonin biosynthesis
      in light-primed aged rats.

PMID- 9564635
TI  - The effect of MAO-A inhibition and cold-immobilization stress on N
      acetylserotonin and melatonin in SHR and WKY rats.
AB  - Selective monoamine oxidase (MAO) A inhibitors and cold-immobilization stress
      (which increases the production of the endogenous MAO-A inhibitor, tribulin)
      stimulate rat pineal melatonin biosynthesis in Sprague-Dawley and Fisher 344N
      rats. Considering the hyperactive sympathetic response of the hypertensive rats,
      it was interesting to compare the effect of clorgyline and cold-immobilization
      stress on pineal melatonin and related indoles levels in SHR and WKY rats (HPLC
      fluorimetric method). Clorgyline (0.5 mg/kg and 1.5 mg/kg, sc) induced a higher
      elevation of pineal melatonin and N-acetylserotonin (NAS) in SHR than in WKY
      rats. Cold immobilization stress resulted in lower serotonin, and higher NAS
      levels in SHR than in WKY rats with similar elevations in melatonin levels. Our
      results suggest increased serotonin conversion into NAS and decreased NAS
      conversion into melatonin with decreased production of tribulin in SHR in
      comparison with WKY rats.

PMID- 9564636
TI  - The influence of the antidepressant pirlindole and its dehydro-derivative on the
      activity of monoamine oxidase A and GABAA receptor binding.
AB  - The influence of pirlindole and dehydro-pirlindole on GABAA receptor binding and
      MAO-A activity was investigated in vitro. Inhibition of rat brain and human
      placenta MAO-A by both compounds was much more potent (with IC50 range 0.3-0.005
      microM) than that of GABAA receptors. Pirlindole was inactive as a GABA
      antagonist. Dehydro-pirlindole exhibited selective blockade of GABA-A receptors
      with EC50 12 microM. Effects of both compounds on MAO-A activity were partially
      reversible. Data obtained suggest that in contrast to pirlindole dehydro
      pirlindole may act not only as a MAO-A inhibitor but also as a potent GABAA
      receptor blocker.

PMID- 9564637
TI  - "In vitro" effect of some 5-hydroxy-indolalkylamine derivatives on monoamine
      uptake system.
AB  - Three different indolalkylamine derivatives (FA 102, FA 69, FA 70) having in
      common an -OH group at 5 position of the indole ring and differing in the
      presence of a methyl group at the N or the acetylenic group of the side chain,
      have been synthesized and assayed as monoamine oxidase-A (MAO-A) [E.C.1.4.3.4]
      inhibitors. They were effective inhibitors with, in some cases, similar potencies
      to clorgyline. "In vitro" experiments were performed on rat brain synaptosomes to
      investigate whether these MAO-A inhibitors had any effect on noradrenaline (NA),
      dopamine (DA) and 5-hydroxytryptamine (5-HT) transport systems in different rat
      brain regions. The effect of these drugs were compared with those of clorgyline
      and 1-deprenyl. FA 102, FA 69, FA 70 behaved as inhibitors of 3H-monoamine uptake
      with similar rank of order of potency for amine uptake inhibition: 5-HT > DA >
      NA. The IC50 values for FA 102, FA 69, FA 70, respectively, were: 17 microM, 60
      microM, 18 microM for 5HT uptake in cortex and 37 microM, 55 microM and 20 microM
      in hippocampus; 70 microM, 385 microM for NA uptake in cortex and 315 microM, 255
      microM and 600 microM in hypothalamus; 270 microM, 160 microM, 40 microM for DA
      uptake in striatum. 1-Deprenyl was a very poor inhibitor of monoamine uptake,
      whereas clorgyline behaved similarly to these indolalkylamine derivatives.
      Comparing these results with the IC50 values of citalopram, nisoxetine and
      GBR12909, specific and selective inhibitors of 5-HT, NA and DA transport systems
      respectively, indicated that these indolalkylamine derivatives interact more
      strongly with the 5HT uptake system.

PMID- 9564638
TI  - N-alkyloxycarbonyl derivatives of ethylene diamine as monoamine oxidase
      inhibitors.
AB  - A series of urethane type derivatives of ethylene diamine (EDA) was synthesised
      and tested as inhibitors of monoamine oxidase (MAO) A and B. Nature of aromatic
      ring and a position of substituents in it were important for the inhibitory
      activity. Chlorobenzyloxycarbonyl-EDA derivatives exhibited selective inhibition
      of MAO-A with 3,4-Cl2-C6H4CH2OCO-EDA being a most potent and selective MAO-A
      inhibitor (IC50 4 microM). Within the compounds studied, 3,4-dichloro
      benzyloxycarbonyl-EDA exhibited most potent inhibition of MAO-A. This compound
      inhibited the activity of rat liver MAO-A non-competitively with Ki (slope) value
      of 3.6 microM, whereas the inhibition of rat liver MAO-B was competitive with Ki
      (slope) value of 56 microM (not shown). 2.4-Dichlorobenzyloxycarbonyl-EDA also
      inhibited rat liver MAO-A in a non-competitive manner with Ki of 14.6 microM.

PMID- 9564639
TI  - "Add-back" therapy for endometriosis in adolescents.
AB  - OBJECTIVE: To review the impact of gonadotropin-releasing hormone agonists (GnRH
      as) on bone mass in adolescents and options for GnRH-a with "add-back" for long
      term therapy for adolescents with endometriosis not responding to conventional
      therapy. STUDY DESIGN: Literature research. RESULTS: The use of GnRH-a plus add
      back therapy has not been specifically studied in the adolescent population, and
      thus the ideal dosage of add-back sex steroids for adolescents has not been
      delineated. CONCLUSION: GnRH-a plus add-back can be considered for usage in
      adolescents with endometriosis who are refractory to conventional therapy, but
      steroids are needed to determine the ideal dosage and long-term effects.

PMID- 9564640
TI  - Multiple birth prevalence in The Netherlands. Impact of maternal age and assisted
      reproductive techniques.
AB  - OBJECTIVE: To evaluate the impact of maternal age and use of fertility drugs on
      multiple birth prevalence from 1970 to 1995 in the Netherlands. STUDY DESIGN: A
      population-based survey was carried out in which data were collected from the
      Centraal Bureau voor Statistiek, the Institute of Medical Statistics and from all
      clinics for in vitro fertilization. RESULTS: In the last two decades, the
      prevalence of multiple births, especially of twin and triplet births, has
      increased significantly. Three possible explanations for this phenomenon are: (1)
      introduction of assisted reproductive techniques in combination with fertility
      drugs; (2) increasing maternal age; and (3) decreasing fecundity with increasing
      maternal age, resulting in more fertility treatments. A surplus of 1,366 twins
      was born in 1995 as compared to 1975. The expected excess of twins was 1,368, of
      which 104 (7.6%) were a result of the increase in total births in 1995, 583
      (42.6%) were due to maternal age > 29 years, and, respectively, 330 (24.1%) and
      351 (25.7%) twins were due to in vitro fertilization treatment and intrauterine
      insemination. CONCLUSION: The delay in achieving pregnancy and the use of
      fertility-promoting therapies profoundly affect the prevalence of multiple
      pregnancies in a given country. The general population should be informed of this
      risk.

PMID- 9564641
TI  - Devices for endometrial sampling. A comparison.
AB  - OBJECTIVE: To compare the clinical performance of two endometrial sampling
      devices, the GynoSampler and Pipelle. STUDY DESIGN: During a single office visit,
      gynecology patients at Women's Hospital, Los Angeles, and the teaching clinic of
      the University of Florida Health Science Center, Jacksonville, underwent two
      endometrial biopsies, one with each device. The specimen adequacy, pain
      associated with the sampling procedure and ease of use of the two devices were
      compared. RESULTS: One hundred women, 50 at each clinical center, were evaluated.
      No significant differences in specimen adequacy were noted, with at least 90% of
      specimens retrieved with each device sufficient for diagnosis. Patient discomfort
      ratings were similar for the two devices. However, physicians performing the
      biopsies noted that the GynoSampler device was easier to use than the Pipelle
      based on three parameters (P < .05). CONCLUSION: Although the GynoSampler and
      Pipelle appear comparable from the perspectives of diagnostic performance and
      patient discomfort, the GynoSampler was easier to use.

PMID- 9564642
TI  - Clomiphene citrate-resistant polycystic ovary syndrome. Preventing
      multifollicular development.
AB  - OBJECTIVE: To determine the efficiency and comparison of two different protocols,
      human menopausal gonadotropin (hMG) plus gonadotropin-releasing hormone analog
      (GnRH-a) and low-dose hMG to reduce multifollicular development in clomiphene
      resistant polycystic ovary syndrome (PCOS) patients. STUDY DESIGN: Prospective
      comparative and pilot study in 20 patients for 31 cycles. The first group (n =
      10) was treated with buserelin acetate, 600 micrograms/d, for six weeks before
      ovulation induction with hMG in conventional doses for 14 cycles. The other group
      (n = 10) was treated only with low-dose hMG for 17 cycles. All cycles were
      compared in terms of the number of follicles per cycle, cycles human chorionic
      gonadotropin withheld, estradiol level on ovulation day, treatment duration and
      number of ampules used per cycle. In addition, the outcome of cycles and
      complications of multifollicular development, ovarian hyperstimulation syndrome
      (OHSS) and multiple pregnancy were determined. RESULTS: As compared with the GnRH
      a + hMG protocol, the low-dose hMG protocol yielded less multifollicular (57.1%
      vs. 17.6%) and more monofollicular (35.7% vs. 70.6%) development. Consequently,
      less OHSS (21.4% vs. 0%) and multiple pregnancy (10% vs. 0%) occurred in the low
      dose group. CONCLUSION: Low-dose hMG therapy has distinct advantages in
      eliminating multifollicular development and related complications in clomiphene
      citrate-resistant PCOS patients. The addition of GnRH-a to gonadotropins does not
      change the incidence of multifollicular development.

PMID- 9564643
TI  - Midtrimester amniocentesis. Influence of operator caseload on sampling
      efficiency.
AB  - OBJECTIVE: To evaluate the impact of operator caseload on the sampling efficiency
      for early and standard, midtrimester amniocentesis. STUDY DESIGN: Prospective
      ascertainment of genetic amniocenteses performed during 36 months, grouped into
      early (13-14 weeks' gestation) and standard procedures (15-20 weeks' gestation).
      Details of each amniocentesis were recorded immediately after sampling, and
      pregnancy outcomes were retrieved via questionnaires completed by the delivering
      physician. Sampling efficiency was evaluated separately in the early and standard
      cohorts in relation to operator caseload. RESULTS: In total, 193 and 707 patients
      underwent early and standard amniocentesis, respectively. Forty of 46 physician
      operators performed < 50 total procedures during the study interval (group A).
      When compared to operators performing > or = 50 cases (group B, n = 6), a higher
      rate of single-pass success was noted among group B physicians for both early and
      standard procedures (A vs. B, early: 40/45 vs. 145/148, P = .018; standard:
      243/295 vs. 384/412, P < .0001). Logistic regression confirmed an independent
      effect of physician caseload on sampling efficiency and a significant interaction
      between physician caseload and simultaneous ultrasound guidance in predicting
      single-attempt success. CONCLUSION: Operator caseload directly influenced
      sampling efficiency for both early and standard, midtrimester amniocentesis.

PMID- 9564644
TI  - Good luck rites in contemporary infertility.
AB  - OBJECTIVE: To explore whether contemporary women use good luck rites in the
      infertility situation. STUDY DESIGN: Prospective study in a tertiary infertility
      center where women were asked to describe any type of good luck act performed on
      the day of critical medical intervention (either intrauterine insemination or
      embryo transfer) to achieve pregnancy. RESULTS: Four hundred thirty-eight
      consecutive infertile women participated. Good luck rituals, as defined by
      patients, included prayer, wearing of objects, fantasies and other acts performed
      specifically on the day of the medical intervention. While 40% of the study
      population reported engaging in a good luck act prior to intrauterine
      insemination of embryo transfer, there was no significant difference in pregnancy
      rates observed in women reporting utilization versus nonutilization of fertility
      rituals. CONCLUSION: This study indicated that good luck rites are commonly
      performed by women undergoing infertility procedures on the day of a critical
      intervention. The fact of their common presence attests to their importance for
      the well-being of the individual; however, there is no evidence of direct benefit
      in terms of higher pregnancy rates. The possibility of secondary benefits needs
      to be explored further.

PMID- 9564645
TI  - Fetal loss after early detection of heart motion in infertility patients.
      Prognostic factors.
AB  - OBJECTIVE: To evaluate the incidence and prognosticators of spontaneous abortion
      (< 20 weeks' gestation) in an infertile population after early documentation of
      fetal cardiac activity. STUDY DESIGN: Retrospective chart review. We examined the
      incidence of spontaneous abortion in 231 clinical pregnancies with 259 fetuses
      documented to be viable by transvaginal sonography 28-38 days after ovulation.
      The population was an unselected group of infertility patients with no history of
      recurrent pregnancy loss. Maternal age and presence of multiple gestations were
      analyzed as separate variables by chi 2 testing. RESULTS: The incidence of
      spontaneous abortion among all fetuses was 9.6% (95% confidence interval [CI],
      6.1-13.2%) and among singleton gestations was 7.7% (95% CI, 4.0-11.3%). Women
      with multiple gestations were more likely to suffer spontaneous fetal loss as
      compared to women with singleton gestations (18 vs. 7.6%, P < .05). In addition,
      women aged 35 and above with singleton pregnancies showed a significantly
      increased rate of fetal loss (13.4 vs. 4.9%, P < .05) when compared with younger
      women. CONCLUSION: Women > or = 35 years old and those with multiple gestations
      were significantly more likely to suffer late first- or early second-trimester
      fetal loss even after detection of fetal cardiac activity. These patients should
      be counseled differently than younger women with singleton pregnancies, and
      increased monitoring may be indicated.

PMID- 9564646
TI  - Laparoscopy for pelvic pain in the Mayer-Rokitansky-Kuster-Hauser syndrome. A
      case report.
AB  - BACKGROUND: The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome occurs in 1 of
      every 4,000-5,000 female births. It is characterized by normal external
      genitalia, an absent vagina, absent or rudimentary uterus, and normal fallopian
      tubes and ovaries. When associated with a rudimentary uterine horn, cyclic
      catamenial pelvic pain may result. The standard procedure for pain relief has
      been removal of the uterine horn by laparotomy. CASE: A rudimentary uterine horn
      was diagnosed in a woman with MRKH syndrome who developed monthly severe pelvic
      pain. Removal of the structure was performed via laparoscopy. The patient had
      complete resolution of her pain. CONCLUSION: As an alternative to laparotomy,
      laparoscopic resection of a rudimentary horn in patients with MRKH syndrome is
      both feasible and beneficial in the treatment of pelvic pain.

PMID- 9564647
TI  - Fetal bradycardia secondary to magnesium sulfate therapy for preterm labor. A
      case report.
AB  - BACKGROUND: Alterations in fetal heart rate variability and baseline may be seen
      with maternal administration of magnesium sulfate. In this case, a dose-related
      decrease in the baseline fetal heart rate was observed in association with
      magnesium sulfate administration. CASE: A primiparous woman was given parenteral
      magnesium sulfate for preterm labor. After tocolytic administration, the fetal
      heart rate baseline decreased to 110 beats per minute (bpm) from its initial rate
      of 140 bpm, although good variability was maintained. Increasing the dosage was
      accompanied by a further drop in the baseline heart rate, to 100 bpm. Fetal
      echocardiography was normal except for sinus bradycardia. Stopping magnesium
      sulfate administration was accompanied by a return to the pretherapy baseline
      heart rate. The pregnancy progressed without any further complications, and a
      healthy infant was delivered three weeks later. CONCLUSION: Maternal
      administration of magnesium sulfate may be associated with a profound decrease in
      the baseline fetal heart rate, resulting in fetal sinus bradycardia.

PMID- 9564648
TI  - Bilateral hip dysplasia. A case report.
AB  - BACKGROUND: Hip dysplasia affects 1% of newborns. Our health system screening
      begins at birth, and our educational system requires health screens at various
      ages, so physicians in this country rarely find an adult with an undiagnosed
      congenital condition. CASE: Bilateral hip dislocation was diagnosed on a 20-year
      old, nulliparous woman who had just arrived from Puerto Rico. She tolerated her
      abnormal gait well, unaware of the condition of her hips. After an unremarkable
      prenatal course, she was admitted at term with ruptured membranes for stimulation
      of labor. She developed secondary arrest of labor, and a healthy, 3,180-g, female
      infant was delivered by cesarean. CONCLUSION: In hip dysplasia, early diagnosis
      (and therapy) prevents long-term consequences.

PMID- 9564649
TI  - Laparoscopic Irving tubal sterilization. A case report.
AB  - BACKGROUND: Very little literature exists on the surgical management of failed
      tubal ligation. However, a review of the literature confirms that the failure
      rate of an Irving tubal sterilization is far lower than is associated with
      partial salpingectomy or unipolar coagulation. CASE: A laparoscopic Irving
      procedure was performed in a woman whose postpartum partial salpingectomy failed.
      CONCLUSION: To our knowledge, this is the first report of an Irving sterilization
      performed by laparoscopy. Laparoscopic Irving tubal sterilization can be an
      effective alternative to fimbriectomy or salpingectomy for failed primary tubal
      sterilization.

PMID- 9564650
TI  - Fetal RhD genotyping by analysis of maternal blood. A case report.
AB  - BACKGROUND: Prenatal determination of fetal rhesus D (RhD) status is desirable in
      pregnancies in sensitized, RhD-negative women to prevent hydropic degeneration of
      the fetus. Recently, a polymerase chain reaction (PCR) test on amniocytes or
      chorionic villi has been in use to demonstrate the RhD status of the fetus in
      sensitized pregnancies. A more advisable, noninvasive approach is to determine
      the fetal RhD group from fetal cells circulating in maternal blood. CASE: We
      report on a prenatal diagnosis where RhD-positive cells could be detected from
      peripheral blood of a sensitized, RhD-negative mother. The presence of an RhD
      positive fetus was confirmed by subsequent amplification of fetal DNA obtained by
      chorionic villus biopsy. CONCLUSION: In sensitized pregnancies, the number of
      fetal cells in maternal blood seems to be high enough to be detected by PCR in
      every case.

PMID- 9564651
TI  - Laparoscopic management of rudimentary horn pregnancy. A case report.
AB  - BACKGROUND: Rudimentary uterine horn pregnancy is a very rare condition. Removal
      of a rudimentary horn is required as soon as a pregnancy is confirmed because
      most pregnancies in a rudimentary uterine horn rupture in the first or second
      trimester. CASE: A 22-year-old woman was admitted to our hospital because an
      ectopic pregnancy was suggested by ultrasonographic examination at another
      hospital. A rudimentary uterine horn pregnancy was suspected from transvaginal
      ultrasonography. The patient was treated with laparoscopic surgery at 7 weeks of
      gestation. The pregnant rudimentary horn was removed laparoscopically by use of
      an automatic stapling device. The postoperative course was uneventful.
      CONCLUSION: This is the first report of laparoscopic resection of a pregnant
      rudimentary uterine horn. Laparoscopic management of such a pregnancy may reduce
      operating time and peritoneal damage.

PMID- 9564652
TI  - Thrombocytopenia with the HELLP syndrome. Report of two cases with reversal in
      normotensive and nonproteinuric gravidas.
AB  - BACKGROUND: In the absence of hypertension and proteinuria, pregnant women with
      hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) present
      a diagnostic and therapeutic problem. CASES: Two atypical cases occurred of HELLP
      syndrome diagnosed by hemolysis, elevated liver enzymes and low platelet count.
      The patients presented early in the third trimester with epigastric pain and
      lacked the usual signs of preeclampsia, such as hypertension and proteinuria. The
      patients were managed expectantly; during this time they became hypertensive, but
      the thrombocytopenia resolved. CONCLUSION: Pregnant women with hemolysis,
      elevated liver enzymes and thrombocytopenia who do not have hypertension or
      proteinuria should undergo complete diagnostic evaluation. If other etiologies
      are ruled out, the patient should be managed as appropriate for severe
      preeclampsia complicated by the HELLP syndrome.

PMID- 9564653
TI  - Incidental finding of Zygomyceteslike hyphae in the placenta. A case report.
AB  - BACKGROUND: Zygomycetes is a class of saprophytic fungi causing opportunistic
      infections. These fungi can cause six distinct clinical manifestations, which can
      be fatal without rapid diagnosis and treatment. The fungi have a predilection for
      blood vessel invasion, causing thrombosis, infarction and necrosis of the tissue.
      CASE: A 25-year-old black woman, a drug abuser, delivered a female infant and the
      placenta en route to the hospital. The estimated gestational age of the infant
      was 35 weeks. The infant and mother had an unremarkable hospital course.
      Evaluation of the placenta revealed extensive involvement of the membranes,
      umbilical cord and chorionic plate by fungal hyphae without any surrounding
      inflammation. These hyphae were seen invading blood vessels, but there was no
      evidence of thrombosis or necrosis. The morphology of the hyphae was consistent
      with Zygomycetes. The mother was contacted and claimed to be well. CONCLUSION:
      Only one case of placental involvement by Mucor has been published since 1966.
      Despite the observation of Zygomyceteslike hyphae in the placenta, both the
      mother and infant were reported to be doing well.

PMID- 9564655
TI  - Heterotopic triplet pregnancy. Report of a case with successful twin intrauterine
      gestation.
AB  - BACKGROUND: Reports of coexisting multiple intrauterine pregnancies and ectopic
      pregnancy are extremely rare. We present one case with early sonographic
      diagnosis of heterotopic pregnancy, successful laparoscopic treatment and a
      subsequent normal pregnancy course and outcome of the intrauterine twin
      gestation. CASE: A 29-year-old woman, gravida 1, para 0, presented for her first
      prenatal visit at 5 weeks of gestation with pelvic pain. She had conceived with
      75 IU leutinizing hormone and follicle-stimulating hormone and homologous
      intrauterine insemination. The sonogram confirmed a dichorionic twin intrauterine
      pregnancy and left tubal pregnancy at 7 weeks of gestation. The patient underwent
      a laparoscopic left salpingostomy and removal of the ectopic pregnancy. Level II
      sonogram showed a grossly unremarkable twin gestation at 20 weeks. Labor was
      induced at 37 weeks of gestation due to mild preeclampsia and underwent vaginal
      delivery without difficulties. The first twin was a girl, weighing 2,722 g, with
      Apgar scores of 9/9. The second twin, a boy, was delivered 10 minutes later,
      weighing 2,863 g, with Apgar scores of 9/9. CONCLUSION: Early sonography is
      essential for the diagnosis of heterotopic pregnancy, and timely surgical
      intervention can save the intrauterine twin gestation, with a subsequent normal
      pregnancy course and outcome.

PMID- 9564654
TI  - Spontaneous rupture of a primigravid uterus secondary to placenta percreta. A
      case report.
AB  - BACKGROUND: Uterine rupture secondary to placenta percreta has been observed in
      multiparous patients. These cases are typically associated with a prior history
      of uterine trauma or infection: hysterotomy, myomectomy, cornual resection,
      dilatation and curettage, manual removal of the placenta or endometritis.
      Spontaneous rupture of the primigravid uterus without a history of trauma or
      infection is an exceedingly rare occurrence. This case represents the second
      reported in the medical literature and the first to result in a live-born infant.
      CASE: A 23-year-old, African American primigravida at 26 weeks' gestation
      presented with acute-onset abdominal pain, severe hypotension, tachycardia and
      fetal heart rate decelerations. Blood product replacement was initiated, and an
      emergency laparotomy was performed for a presumptive diagnosis of intraabdominal
      hemorrhage. A significant hemoperitoneum was encountered, with the fetus floating
      freely in the peritoneal cavity. The uterus had a fundal rupture with a
      clinically apparent placenta percreta that necessitated performing a total
      abdominal hysterectomy. The patient recovered uneventfully, and the infant
      survived without significant morbidity. CONCLUSION: Spontaneous rupture of the
      primigravid uterus can occur in the absence of a history of uterine trauma or
      infection. If a gravid woman presents with hypotension, abdominal pain and fetal
      distress, the differential diagnosis should include rupture of the uterus,
      regardless of parity or gynecologic history. Rapid diagnosis, blood product
      replacement and emergency laparotomy are the key steps in successful management.

PMID- 9564656
TI  - The second decade of GnRH agonists. In vitro fertilization and endometriosis. A
      symposium.

PMID- 9564657
TI  - GnRH agonists and in vitro fertilization.
AB  - GnRH agonists (GnRH-a) were introduced into in vitro fertilization (IVF)
      superovulation regimens in the late 1980s and have become established as a
      component of standard regimens in most centers worldwide. Each style of GnRH-a
      regimen (long, short or ultrashort) is associated with particular advantages and
      disadvantages. In general the "long protocol" approach tends to be the most
      widely used. The pros and cons of these different approaches are discussed, as
      are issues concerned with the management and safety of GnRH-a regimens in IVF.

PMID- 9564658
TI  - Status of current research on endometriosis.
AB  - Endometriosis, a benign gynecologic disorder, occurs in about 10% of women of
      reproductive age and in up to 50% of women with infertility. Endometriosis is
      defined as the presence of endometrial glandular and stromal cells outside their
      normal location in the uterus. Commonly affected areas in the abdominopelvic
      cavity include the ovaries, the cul-desac and other kinds of pelvic peritoneum,
      bowel and diaphragm. Rarely is it found in extraabdominal sites, including the
      pleura and pericardium. While it is not a malignant disorder, endometriosis
      exhibits cellular proliferation, cellular invasion and neoangiogenesis. The
      steroid hormone dependence of endometriosis is underscored by its appearance
      during the reproductive years. Furthermore, the progress of this enigmatic
      disease can be tempered by administration of antiestrogens, inhibitors of
      endogenous estradiol production, and hormonal and surgical castration. It is a
      disorder that markedly affects well-being and physical and emotional health in
      women. Research on the pathogenesis of endometriosis currently interfaces with
      four areas of basic research, including the fields of genetics, environmental
      science, cancer biology and immunology. Here we focus on current research in the
      latter two disciplines and their relevance to endometriosis research.

PMID- 9564659
TI  - The genetics of endometriosis.
AB  - Endometriosis is probably a complex trait, like diabetes, hypertension or asthma,
      which implies that the disease is caused by an interaction between multiple genes
      and the environment. This paper reviews the evidence, in both human and nonhuman
      primates, that supports the theory of a genetic basis to endometriosis. The
      OXEGENE study, which aims to identify susceptibility genes in endometriosis
      through linkage analysis, is also described. DNA is being collected from families
      containing at least two sisters with surgically confirmed revised American
      Fertility Society stage III and IV disease to carry out a genome-wide search for
      susceptibility genes. Candidate genes involved in galactose metabolism and dioxin
      detoxification are also being analyzed. The identification of genes conferring
      susceptibility to endometriosis may lead to a better understanding of disease
      etiology and, in time, improved therapeutic strategies and diagnostic methods.

PMID- 9564660
TI  - Modern concepts of endometriosis. Classification and its consequences for
      therapy.
AB  - OBJECTIVE: To review the development of the American Society for Reproductive
      Medicine (ASRM) classification forms for endometriosis and assess efforts to
      validate their clinical utility. STUDY DESIGN: The relevant medical literature
      was reviewed. RESULTS: ASRM has established classification forms for
      endometriosis in women with infertility and pelvic pain. The utility of these new
      forms has not been assessed. Studies using earlier versions of the ASRM
      classification reported that the stage of disease correlates better with pain
      symptoms than fertility outcome. CONCLUSION: The ASRM classification form for
      infertility and the form to assist in the management of pelvic pain in women with
      endometriosis permit clear documentation of the extent and morphologic type of
      disease. Further studies are needed to refine the classification and enhance its
      predictive ability.

PMID- 9564661
TI  - Periovarian peritoneal adhesions in women with endometriosis. Structural
      patterns.
AB  - OBJECTIVE: To draw attention to the structural features of adhesions associated
      with pelvic endometriosis since they are less well studied than endometriosis
      proper. STUDY DESIGN: Sixty-two samples of periovarian adhesions were
      laparoscopically obtained from 24 infertile women 26-38 years of age and were
      prepared for detailed histologic analyses. RESULTS: Macroscopically, the
      adhesions were either velamentous or cordlike and grossly were free of
      endometriosis. Most adhesions were attached to the connective tissue of the
      ovarian tunica albuginea; in two cases they were attached to the corpus luteum.
      Upon microscopic analysis, velamentous adhesions consisted of fibrous sheets of
      collagen connective tissue, with the surface lined with single-layered coelomic
      epithelium. The cord-like adhesions consisted of "hyalinized" fibrous tissue and
      were either avascular or vascularized. Irregular cystic or tubular structures
      that could be regarded as endometriosis were found in four patients. Hyaline
      cartilage within the tissue of the adhesion was an unexpected finding in one
      patient. CONCLUSION: Microscopic analysis permitted grouping of the adhesions in
      the following way: (1) Connective tissue adhesions (23 patients) with the
      following subcategories: (A) fibrous, either avascular or encompassing
      degenerating blood vessels (6 patients); (B) vascularized, containing
      granulomatous tissue (12 patients); (C) vascularized with stromoglandular
      endometrioid cysts or tubules (4 patients); (D) rare types, such as that
      encompassing hyaline cartilage (1 patient). (2) Fibrin adhesions (1 patient).
      From the clinical point of view, the presence of endometrial tissue within
      adhesions raises the question of whether there is a need for removal, rather than
      just lysis, of adhesions to avoid persistent pain.

PMID- 9564662
TI  - Endometriosis. Current issues in diagnosis and medical management.
AB  - OBJECTIVE: To explore the hypothesis that endometriosis is a disease not just
      because it exists but because it is functionally active. STUDY DESIGN:
      Qualitative research analyzing the morphologic appearances of endometriosis and
      the clinical effect of medical therapies. RESULTS: Analysis of the appearances of
      symptomatic endometriosis demonstrates that the ectopic endometriumlike tissue
      mimics eutopic endometrium but with loss of polarization. Ectopic implants
      resembling superficial endometrium are hemorrhagic and associated with adhesion
      and pseudocyst or endometrioma formation. Ectopic implants resembling basal or
      junction zone endometrium are associated with nodular adenomyotic lesions in the
      posterior fornix and pelvic supportive structures. They are characterized by
      smooth muscle hyperplasia and T-lymphocyte aggregates. CONCLUSION: Medical
      therapy has been shown to be very efficient in reducing pelvic pain as soon as
      amenorrhea is created and maintained. Regression, but not elimination, of the
      implant is obtained by medical therapy. Clinical data support the hypothesis that
      the efficacy of medical therapy is largely achieved by preventing cyclic bleeding
      in the implants.

PMID- 9564663
TI  - Endometriosis and the estrogen threshold theory. Relation to surgical and medical
      treatment.
AB  - Estrogen-dependent diseases often regress when estrogen production is reduced.
      Endometriosis is an estrogen-responsive disease, and the pelvic pain associated
      with it improves when estrogen production is reduced with bilateral oophorectomy
      or chronic gonadotropin releasing hormone (GnRH) agonist treatment.
      Unfortunately, reduction of estrogen production is associated with adverse side
      effects, such as vasomotor symptoms and bone loss. In women with endometriosis
      and pelvic pain, the combination of bilateral oophorectomy plus postoperative low
      dose estrogen treatment produces sustained improvement in pain symptoms and
      reduces the hypoestrogenic side effects associated with bilateral oophorectomy.
      In a parallel manner, chronic GnRH agonist treatment plus low-dose steroid
      therapy (estrogen plus progestin or progestin only) is effective in the treatment
      of pelvic pain caused by endometriosis and reduces the hypoestrogenic effects
      associated with hypoestrogenism caused by the GnRH agonist. Since chronic GnRH
      agonist treatment is reversible and avoids surgery, it may become an important
      alternative to bilateral oophorectomy for the treatment of endometriosis.

PMID- 9564664
TI  - Comparative effects of GnRH agonist therapy. Review of clinical studies and their
      implications.
AB  - OBJECTIVE: To understand why differences in gonadotropin releasing hormone (GnRH)
      agonist therapeutic protocols may affect their efficacy and safety profiles, to
      understand the important study design facets regarding the literature on GnRH
      agonist treatment of endometriosis and to compare the efficacy and side effect
      profiles of FDA-approved GnRH agonist therapies used for the management of
      endometriosis and consider the implications. STUDY DESIGN: Review of the English
      language literature regarding the use of GnRH agonists for the management of
      endometriosis. RESULTS: A limited number of studies are available that directly
      compare the effects of different GnRH agonists. However, contrary to medical
      opinion, it appears that there are significant differences between GnRH agonist
      therapies. CONCLUSION: The data suggest that it may be possible to reduce doses
      or alter regimens of GnRH agonists so as to reduce side effects while maintaining
      efficacy.

PMID- 9564665
TI  - Human issues and medical economics of endometriosis. Three- vs. six-month GnRH
      agonist therapy.
AB  - OBJECTIVE: To project the efficacy and economic consequence of short-term
      intranasal gonadotropin-releasing hormone agonist (GnRH-a) for diagnosis of and
      therapy for endometriosis. STUDY DESIGN: Multicenter, placebo-controlled clinical
      trials of GnRH-a comparing three vs. six months of treatment, three months of
      retreatment and three months of postoperative treatment for the symptoms and
      signs of laparoscopically diagnosed endometriosis. RESULTS: The reduction in
      symptoms and signs of endometriosis was similar at the end of three months to the
      relief at six months. Retreatment was as effective as initial treatment, and the
      return of symptoms after laparoscopic surgery plus postoperative treatment for
      three months was delayed by approximately 18 months as compared to surgery alone.
      The projected charges for the surgical approaches (laparoscopy or
      minilaparoscopy) to diagnosis and therapy were 50-60% greater than those for the
      medical approach. CONCLUSION: GnRH-a administration for three months could be a
      cost-effective approach to the presumptive diagnosis and treatment of
      endometriosis among women with chronic pelvic pain.

PMID- 9564666
TI  - Endometriosis. The case for early, aggressive treatment.
AB  - While the debate rages on regarding how metabolic and immunologic changes fit
      into the pathophysiology of endometriosis, the clinician must nonetheless make
      decisions regarding treatment. This article examines the relevant literature,
      with particular emphasis on immunologic aspects, nonclassic, early and deep
      disease as well as data on progression, recurrence and effects of treatment, to
      propose innovations in the management of early-stage disease. All symptomatic
      early-stage disease should be treated aggressively--even after conservative
      surgical resection of all apparent endometriosis, adjunct medical treatment in
      the form of a gonadotropin-releasing hormone agonist should be strongly
      considered.

PMID- 9564667
TI  - Combined treatment of endometriosis. GnRH agonists and laparoscopic surgery.
AB  - Use of preoperative gonadotropin-releasing hormone (GnRH) agonists may be
      beneficial in the case of laparoscopic surgery for large endometriomas. Further
      studies are necessary to confirm the claim that preoperative GnRH agonists
      facilitate laparoscopic surgery for endometriosis. Use of GnRH agonists after
      laparoscopic treatment of endometriosis has beneficial effects in preventing the
      recurrence of pelvic pain associated with endometriosis.

PMID- 9564669
TI  - Importance of lay organizations for coping with endometriosis.
AB  - OBJECTIVE: To evaluate the coping resource of social support for women with
      endometriosis. STUDY DESIGN: The social support experience of 46 women who
      participate in an endometriosis support group on the internet were examined. A
      questionnaire was designed to explore the social support experiences of these
      women in four relationship categories: spouse/partner, friends/extended family,
      other with endometriosis and health care providers. RESULTS: The participants'
      responses were analyzed for themes. Overall themes that emerged from the analysis
      include: the participants wanted to be listened to and believed, they wanted
      their support network to be knowledgeable about endometriosis, they wanted others
      to understand the symptoms of the disease, and they wanted their support system
      to share information about the disease. CONCLUSION: In general, the women with
      endometriosis in this study value connections to other women with endometriosis.
      Also, in general, these women want information from their health care providers
      and others in their support network. Physicians are in a good position to help
      these women connect to a vast network of information and support.

PMID- 9564668
TI  - Bone densitometry as an adjunct to GnRH agonist therapy.
AB  - OBJECTIVE: To outline the optimal use of bone densitometry in women receiving
      gonadotropin releasing hormone (GnRH) agonist therapy. STUDY DESIGN: The use of
      bone densitometry during clinical trials of the use of GnRH agonists in
      endometriosis has resulted in a number of publications with varying conclusions
      about the effects of these agents on the skeleton. A review of this literature,
      taking into account known concepts of bone physiology and the varying quantities
      measured by different bone densitometry devices, was done to place these results
      into a common framework. Within this context, a proposal is made for when and how
      to use various bone densitometry methods in individual patients and how to
      interpret the results properly. RESULTS: Bone density in young women being
      treated for endometriosis is usually within the normal range, with even those 2
      SD below normal not at significant risk of osteoporotic fracture. However, the
      clinical results show that most, if not all, women treated with GnRH agonists
      experience an increase in bone turnover due to estrogen deficiency during
      treatment, and this can result in a transient decrease in bone density. Even
      though the bone is regained after treatment is stopped, it may take years to
      recover fully. For those women who had low bone density to start, they may lose
      sufficient bone to increase their risk of osteoporotic fracture, and it is
      important to identify those individuals before treatment and to monitor them
      carefully. If the result of a peripheral bone density measurement (hand, forearm,
      heel) or central measurement (spine or hip) before treatment is higher than about
      1 SD below a young normal mean, then even if a woman loses some bone, she will
      not have a significant increase in the risk of fracture. However, if a
      measurement is low (> 1 SD below the mean, putting her in the lower 15%), then it
      is advisable to have a spinal measurement by quantitative computed tomography or
      dual energy x-ray absorptiometry before and after therapy to determine what the
      bone changes are and to follow-up after the end of treatment. This is especially
      true if she decides to become pregnant, needs retreatment with a GnRH agonist or
      will be going through natural menopause in the near future; all can cause further
      bone loss. CONCLUSION: Different bone density methods give different information
      and must be interpreted properly when used in evaluating patients on GnRH agonist
      therapy. Any bone measurement may be used to assess skeletal status before
      treatment, but if a peripheral bone measurement is low, it should be followed
      with a spinal measurement by quantitative computed tomography or dual energy x
      ray absorptiometry so that the effect of the treatment can be monitored. Bone
      loss is transient with GnRH treatment, but only spinal measurements have
      sufficient sensitivity to follow patients and evaluate the skeletal changes in a
      meaningful way.

PMID- 9564670
TI  - High resolution recording of late cortical surface potentials N1 and gamma band
      response (GBR).
AB  - The present investigation was conducted to help determine whether source activity
      of the direct recorded N1 response differed from that of the gamma band response
      (GBR). Auditory evoked cortical potential data from two patients with intractable
      epilepsy undergoing prolonged video EEG monitoring after implantation of subdural
      electrodes is reported in this investigation. Evoked responses were recorded to
      1000-Hz tone bursts. The data were then filtered digitally to resolve the GBR.
      The voltage fields were subsequently viewed topographically. Although both
      responses originated in the supratemporal cortex, the N1 and GBR voltage field
      patterns differed. These results are consistent with the view that the sources of
      N1 and the GBR are different, suggesting that these components emanate from
      functionally distinct neuronal pools.

PMID- 9564671
TI  - Seventh survey of audiometric practices in the United States.
AB  - A 5-page questionnaire was sent to 500 audiologists who were randomly selected
      from the directory of members of the American Academy of Audiology to assess the
      clinical practices most commonly used by certified audiologists in the United
      States. Survey content was limited to only those practices and procedures
      routinely used by audiologists across the nation. The current results were then
      compared to those obtained in similar studies conducted in 1971, 1972, 1978,
      1985, 1989, and 1994 to determine which clinical procedures are being retained,
      modified, or replaced.

PMID- 9564672
TI  - Review of hearing aid amplification circuits.
AB  - This review draws upon a range of information concerning the salient
      characteristics of the classes of operation of amplifier circuits commonly used
      in hearing aids. The aim is to help the clinician to develop a broader
      perspective than might be derived from consulting only the popular hearing aid
      trade literature.

PMID- 9564673
TI  - Effects of pre-existing hearing loss on proposed ANSI S12.13 outcomes for
      characterizing hearing conservation program effectiveness: follow-up
      investigation.
AB  - Draft ANSI S12.13 1991 Standard Evaluating the Effectiveness of Hearing
      Conservation Programs presents statistical protocols purportedly sensitive to
      temporary threshold shift (TTS) in occupational hearing conservation program
      (HCP) audiometric databases. Because it is well established that less TTS is
      found in humans with hearing loss than in those with essentially normal hearing,
      one might predict baseline hearing level to be a confounding variable in
      interpreting ANSI S12.13 outcomes, with better-hearing industrial populations
      tending to demonstrate greater year-to-year audiometric variability than poorer
      hearing groups. However, in a large industrial sample from the public domain
      audiometric database, poorer-hearing groups systematically demonstrated greater
      audiometric threshold variability than better-hearing groups, and ANSI S12.13
      outcome magnitudes were highly positively correlated to baseline hearing levels.
      These findings generally do not support notions that ANSI S12.13 outcomes clearly
      provide indirect measures of TTS. HCP managers should exercise extreme caution in
      interpreting ANSI S12.13 outcomes to rate overall program performance. In
      particular, HCP managers should not rely upon these outcomes for decisions
      regarding hearing protection policies without careful consideration of pre
      existing hearing loss in the populations involved.

PMID- 9564674
TI  - Action potential latency shift by rarefaction and condensation clicks in
      Meniere's disease.
AB  - Transtympanic electrocochleography using rarefaction and condensation clicks was
      performed on 122 ears of 112 patients, including 98 ears of 89 patients with
      Meniere's disease (MD) and 24 ears of 23 patients without Meniere's disease
      (NMD). The mean action potential (AP) latency difference between rarefaction and
      condensation clicks was 0.40 +/- 0.37 msec in the MD group and 0.06 +/- 0.07 msec
      in the NMD group (p < .01). An AP latency shift > 0.2 msec was found more often
      in the MD group (62.2% vs 8.3%) and in ears with an enlarged summating potential
      and AP ratio (69.7% vs 36.4%). The results suggest that comparison of rarefaction
      and condensation latencies may serve as a useful addition to electrocochleography
      in the diagnosis of MD.

PMID- 9564675
TI  - Effects of in-situ calibration of click stimuli on the auditory brainstem
      response.
AB  - We studied the effects on the auditory brainstem response (ABR) of applying a
      computerized calibration procedure for click stimuli that corrects for individual
      transducer characteristics and ear canal acoustics. The "calibrated" signal at
      the eardrum possesses a nearly flat spectrum from 500 to 10,000 Hz. ABRs were
      recorded from normal-hearing subjects using both calibrated and uncalibrated
      clicks. The preponderance of energy for the latter stimulus was between 1000 and
      4000 Hz. When compared to the responses evoked by the uncalibrated signal, ABRs
      to calibrated clicks displayed shorter component latencies, increased component
      amplitudes, and a more sensitive wave V relative to behavioral threshold.

PMID- 9564676
TI  - Effects of repetition rate, phase, and frequency on the auditory brainstem
      response in neonates and adults.
AB  - This study evaluated the effects of stimulus repetition rate, phase, and
      frequency on the auditory brainstem response (ABR) in normal-hearing neonates and
      adults. In both neonates and adults, the results clearly showed large ABR wave V
      latency differences between condensation and rarefaction for low-frequency
      stimuli. Phase dependent latency effects are believed to be a result of the phase
      sensitive low-frequency neurons. Increasing stimulus repetition rate produced
      greater wave V latency shift in neonates than in adults. The consequences of rate
      changes were independent of stimulus phase and frequency.

PMID- 9564677
TI  - Evaluation of hearing handicap. The American Academy of Otolaryngology and
      American Council of Otolaryngology (AA0-ACO)
AB  - The American Academy of Otolaryngology and American Council of Otolaryngology
      (AAO-ACO) define hearing handicap as a disability to understand sentences under
      everyday vocal and listening conditions, and describe procedures for its
      estimation from pure-tone threshold hearing levels. Research now reveals that the
      AAO-ACO procedures underestimate measured hearing handicap by the equivalent of
      averaged pure-tone threshold losses of 17 dB at high-percentage handicaps to 35
      dB at low-percentage handicaps. It is proposed that AAO-ACO procedures be
      modified as follows: (a) adjust hearing levels for presbycusis when estimating
      handicap due to noise or other factors than presbycusis; (b) change averaged
      hearing level "fences" from present 25 dB to 15 dB for 0 percent and from present
      92 dB to 75 dB for 100 percent handicap; and (c) change weight for "worse" ear
      contribution from present 1/6 to 1/4 for binaural listening.

PMID- 9564678
TI  - Intrasubject reliability of high-frequency (9-14 kHz) thresholds: tested
      separately vs. following conventional-frequency testing.
AB  - Retrospective analysis of hearing-threshold data from a multisite ototoxicity
      monitoring study identified an individualized range of predominantly high
      frequencies (> 8 kHz) that appeared to be highly sensitive to early threshold
      changes caused by ototoxicity. This suggested the potential for a limited
      frequency monitoring protocol that could be conducted rapidly without
      compromising sensitivity to ototoxicity. Such testing would require high
      frequency thresholds to be obtained independently, that is, without prior testing
      at conventional frequencies (0.25-8 kHz). This study was conducted to determine
      the test-retest reliability of isolated threshold testing in a "target" frequency
      range of high frequencies (9, 10, 11.2, 12.5, and 14 kHz) that represented a
      shortened ototoxicity monitoring test. Twenty normal-hearing subjects were
      evaluated over five sessions. During each session, subjects were tested in each
      of two conditions: (1) conventional frequencies (0.25-8 kHz) tested first,
      followed by target frequencies; and (2) target frequencies tested alone
      (isolation condition). Depending on test frequency, reliability of high-frequency
      thresholds was either unchanged or improved in the isolation condition. Although
      these results cannot be generalized to ill hospitalized patients, who may also
      have pre-existing hearing loss, they lay the groundwork for development of a time
      saving limited-frequency test to monitor for ototoxicity in these patients.

PMID- 9564679
TI  - Psychometric adequacy of the Tinnitus Handicap Inventory (THI) for evaluating
      treatment outcome.
AB  - This study assessed the test-retest reliability/repeatability and 95 percent
      confidence intervals (CIs) of the Tinnitus Handicap Inventory (THI) and developed
      categories for classifying self-perceived tinnitus handicap severity. Twenty-nine
      adults with tinnitus as their primary auditory complaint served as subjects. The
      THI was administered on two occasions (mean interval 20 days) using a paper
      pencil format. Results support the contention that the THI is psychometrically
      robust. Specifically, the test-retest reliability/repeatability was high.
      Additionally, the 95 percent CI for the THI was 20-points, indicating that a 20
      point or greater change had to occur from test to retest for a change to be
      considered statistically significant at the 5 percent confidence level. Quartiles
      calculated from raw scores were used to create a matrix of values representing
      tinnitus severity. We conclude that the THI is a brief, easily administered, and
      psychometrically robust measure that evaluates the impact of tinnitus on daily
      living.

PMID- 9564680
TI  - Comment on "Consonant perception in quiet: effect of increasing the consonant
      vowel ratio with compression amplification".

PMID- 9564681
TI  - Genetics and anorexia nervosa: a review of candidate genes.
AB  - Anorexia nervosa is a severe disorder which seems likely to have a multifactorial
      aetiology. However, several studies have stressed that genetic factors play a
      significant role. Epidemiological studies have shown that the lifetime risk for
      first-degree relatives of a patient with an eating disorder is 6% compared to 1%
      among relatives of controls, and a twin study performed on 34 pairs of twins has
      shown a higher concordance rate in monozygotic twins (55%) compared to dizygotic
      twins (7%). The vulnerability component of anorexia nervosa that can be
      attributed to genetic influences has been estimated from twin studies to be
      around 70%. Despite this, few genetic studies have been performed testing the
      role of candidate genes which code for proteins potentially implicated in the
      aetiopathogenesis of the disorder. In this review, genes encoding components of
      the dopamine, serotonin, opiate, and noradrenaline systems are assessed for their
      role in anorexia nervosa. Attention is paid to psychological dimensions, clinical
      symptoms, co-morbidity frequency, pharmacological data, and biological measures
      that characterize anorexia nervosa.

PMID- 9564682
TI  - Possible allelic association of a tyrosine hydroxylase polymorphism with
      vulnerability to alcohol-withdrawal delirium.
AB  - Recently, an association has been reported between schizophrenia and a rare
      allele containing 10-repeats (A10) of a polymorphic tetranucleotide motif in the
      first intron of the tyrosine hydroxylase (TH) gene. The present association
      analysis tested the hypothesis that the A10 candidate allele confers
      vulnerability to alcohol-withdrawal delirium with visual hallucinations. The
      genotype of the TH tetranucleotide polymorphism was assessed in 204 German
      controls and 311 German alcohol-dependent subjects, including 63 alcoholics with
      a history of visual hallucinations during withdrawal delirium. The frequency of
      the A10 allele was significantly increased in the alcoholics with withdrawal
      delirium (3.2%) compared with that in the controls (0.5%; Fisher's exact test: P
      = 0.03, two-tailed; OR (A10+) = 6.85, 95% confidence interval: 1.52-30.79). The
      possible allelic association suggests that allelic variation at the TH locus
      mediates vulnerability to alcohol-withdrawal delirium in a small proportion of
      alcohol-dependent subjects.

PMID- 9564683
TI  - TaqI polymorphic sites at the human dopamine beta-hydroxylase gene possibly
      associated with biochemical alterations of the catecholamine pathway in
      schizophrenia.
AB  - Two parts of the dopamine beta-hydroxylase (DBH) gene, one a 7.5-kb single copy
      fragment (F1) spanning the 5'-flanking region to exon 3 and the second a 9.0-kb
      single copy fragment (F2) spanning exon 3 to exon 7, were amplified by a long PCR
      procedure in 161 unrelated patients with schizophrenia and 67 unrelated control
      subjects. The PCR products were completely digested with the restriction enzyme
      TaqI. These subjects were classified into genetic subgroups according to the TaqI
      restriction fragment length polymorphisms (RFLPs) for the human DBH gene, and the
      association of the TaqI RFLPs with biochemical alterations of the catecholamine
      pathway in schizophrenia was then examined. The frequencies of the two TaqI
      polymorphic sites did not show significant differences between the patients and
      control subjects, but the TaqI RFLPs were found to be associated with biochemical
      alterations of the catecholamine pathway in schizophrenia.

PMID- 9564684
TI  - Lack of association between debrisoquine 4-hydroxylase (CYP2D6) gene
      polymorphisms and schizophrenia.
AB  - Debrisoquine 4-hydroxylase (CYP2D6) is a cytochrome P450 enzyme involved in the
      metabolism of most neuroleptics, which are the drugs of choice for the treatment
      of psychotic symptoms. CYP2D6 in the brain was suggested to be functionally
      similar to the dopamine transporter, thus possibly influencing a neurotransmitter
      system involved in schizophrenia. Swedish schizophrenic patients (n = 124) and
      control individuals (n = 85) were investigated for two CYP2D6 polymorphisms,
      responsible for approximately 90% of mutations leading to poor debrisoquine
      metabolism. No significant CYP2D6 allele or genotype difference was found between
      schizophrenic patients and control individuals. Taken together with previous
      results, no major effect appears to be caused by the CYP2D6 gene on
      schizophrenia.

PMID- 9564685
TI  - Association between functional psychosis and expanded CAG/CTG repeats is not
      explained by health stratification.
AB  - A number of studies have reported an association between large CAG/CTG repeats
      and both schizophrenia and bipolar disorder. Recently, we reported an inverse
      correlation between CAG/CTG repeat size and age in a health-selected population,
      raising the possibility that selection of control groups for physical health was
      a confounding factor in our previous association studies. We investigated this by
      health-selection of patients with schizophrenia and bipolar disorder. The maximum
      CAG/CTG repeat size remained significantly larger in probands with functional
      psychosis compared with control individuals, and in probands with a diagnosis of
      schizophrenia compared with control individuals. The number of probands in the
      healthy bipolar group was small, and although on average this group also had
      longer CAG/CTG repeats than control individuals, this failed to reach statistical
      significance. Our findings do not support the notion that the original results
      with psychosis as a whole, and schizophrenia specifically, are attributable to a
      stratification effect consequent on health selection. Nevertheless, we are unable
      formally to reject the hypothesis that the previously observed difference between
      bipolar probands and control individuals is the result of this phenomenon.

PMID- 9564686
TI  - Systematic search for mutations in the 14-3-3 eta chain gene on chromosome 22 in
      schizophrenics.
AB  - The brain-rich 14-3-3 protein regulates synthesis and excretion of bioamine by
      activating tyrosine and tryptophan hydroxylases, and by exocytosis of
      catecholamines and serotonin. In humans, at least eight subunits of the 14-3-3
      protein family have been isolated. The 14-3-3 eta chain gene is located at
      22q12.1 to q13.1, one of the chromosome regions identified as possibly linked to
      schizophrenia. We systematically searched for nucleotide variants in the coding
      region, 5' and 3' untranslated region, and in the exon-intron boundaries of the
      genomic 14-3-3 eta gene in 24 schizophrenics and 24 controls. Two polymorphic
      sites were found: one in the 5' untranslated region and one in the 3'
      untranslated region. However, no variants predicting amino-acid alterations were
      observed. Similar allelic and genotypic distributions for both polymorphisms were
      found in 308 schizophrenics and 135 controls.

PMID- 9564687
TI  - Familial occurrence of primary premature ejaculation.

PMID- 9564688
TI  - Retinal pigment epithelial transplantation in age-related macular degeneration.

PMID- 9564689
TI  - Retinal pigment epithelial lesions associated with choroidal ischemia in
      preeclampsia.
AB  - PURPOSE: Retinal and choroidal changes are considered uncommon ocular
      complications in preeclampsia. The authors evaluated preeclamptic and eclamptic
      patients to clarify the ophthalmologic features of preeclampsia. METHODS: The
      records of 71 women with severe preeclampsia or eclampsia were reviewed. Lesions
      related to choroidal circulatory disturbance were identified on review of patient
      fundus examinations and fluorescein angiograms. RESULTS: Of 31 women whose
      records were evaluated, serous retinal detachments, yellowish, opaque retinal
      pigment epithelium (RPE) lesions, or both were present in 47 eyes (both lesions
      in 29 eyes, RPE lesions alone in 7 eyes, and serous retinal detachments alone in
      11 eyes). Of the 36 eyes with RPE lesions, 33 (92%) had solitary or grouped
      lesions and 3 (8%) had large geographic lesions. The lesions were most commonly
      observed in the peripapillary area and macula. Lesions resolved without scarring
      in 3 weeks in 30 (83%) of these eyes. There was residual pigmentary mottling in
      three eyes (8.5%); in an additional three eyes (8.5%), all of which had had
      geographic lesions, significant chorioretinal atrophy developed. CONCLUSIONS: The
      results suggest that the incidence of RPE lesions and serous retinal detachments,
      which are transient manifestations of choroidal ischemia, is high in patients
      with severe preeclampsia and eclampsia. These conditions resulted in significant
      scarring in only a small number of patients.

PMID- 9564690
TI  - Scanning laser ophthalmoscope microperimetric assessment in patients with
      successful laser treatment for juxtafoveal choroidal neovascularization.
AB  - PURPOSE: To evaluate fixation stability and changes in retinal function in
      patients with laser scar expansion after successful macular photocoagulation for
      juxtafoveal choroidal neovascularization (CNV). METHODS: A consecutive series of
      35 patients was examined in this prospective study. Only patients who had been
      successfully treated with laser photocoagulation for juxtafoveal CNV and who
      could be followed over a period of at least 6 months were enrolled. Fixation
      stability and localized light sensitivity were examined by microperimetry using a
      scanning laser ophthalmoscope. Visual acuity was measured 2 weeks and 3 and 6
      months after the laser treatment. The correlation between changes in the
      logarithm of the minimum angle of resolution (LogMAR) visual acuity and the
      distance between fixation and the center of the fovea was evaluated. RESULTS: Of
      22 eyes of 20 patients that underwent data analysis, laser scar expansion was
      observed in 16 (72.7%). Ten (62.5%) of the 16 eyes had relative scotomas
      corresponding to the expanded laser scars. Mean laser scar expansion ratio was
      28.7% in the ARMD group and 109.2% in the myopia group, a statistically
      significant difference (P < 0.01). The change in LogMAR visual acuity was
      significantly correlated with the distance of fixation locus from the center of
      the fovea (r = 0.76). CONCLUSIONS: Laser scars produced by photocoagulation for
      juxtafoveal CNV may expand and extend into the fovea, causing secondary retinal
      dysfunction. Scanning laser ophthalmoscopic assessment may be useful in
      evaluating fixation stability and subclinical changes in retinal function
      surrounding the laser scars before visual disturbance appears.

PMID- 9564691
TI  - Lacquer cracks following laser treatment of choroidal neovascularization in
      pathologic myopia.
AB  - BACKGROUND: Lacquer cracks are breaks in the retinal pigment epithelial-Bruch's
      membrane-choriocapillaris complex and are manifestations of pathologic myopia.
      Progressive posterior segment elongation, uveal scleral thinning, and retinal
      pigment epithelial degeneration are thought to create a predisposition for crack
      formation in these eyes. In turn, choroidal neovascularization (CNV) may develop
      within the cracks to produce disciform scarring of the macula. This study
      examined lacquer cracks as a possible consequence of laser photocoagulation of
      CNV. METHODS: From the files of two retinal referral practices, five patients
      were located in whom lacquer cracks developed or expanded after laser
      photocoagulation for macular CNV in pathologic myopia. The mean age of the
      patients was 54.8 years. Four patients were treated with krypton red laser and
      one with an argon laser. Laser settings were available for only one of the
      patients. RESULTS: After laser photocoagulation, lacquer cracks were noted to
      expand in one or two directions from the laser scar between 10 days and 3 months
      of the treatment. The cracks also served as a pathway for progressive or
      recurrent neovascularization. CONCLUSIONS: Although lacquer cracks occur
      spontaneously in pathologic myopia, expansion, elongation, or simple development
      of a crack may occur as a result of laser photocoagulation of CNV. The new cracks
      also serve as a potential risk for recurrent neovascularization. This potential
      adverse complication should be considered in the management of CNV in pathologic
      myopia with laser treatment.

PMID- 9564692
TI  - Cyanoacrylate glue in the repair of retinal detachment associated with posterior
      retinal breaks in infants and children.
AB  - PURPOSE: To share the authors' experience with cyanoacrylate glue in posterior
      retinal breaks associated with retinal detachments in infants and children.
      METHODS: A retrospective study was performed of four consecutive pediatric
      patients who underwent vitreoretinal surgery for retinal detachment associated
      with posterior retinal breaks, for which cyanoacrylate glue was used. RESULTS: In
      three of the four patients, successful retinal reattachment with visual function
      was achieved by vitreoretinal surgery and cyanoacrylate placed on the apposed
      edges of posterior retinal breaks or used to plug a break (postoperative follow
      up was 1.5-2 years). In two successful cases, the glue was applied onto the break
      while the retina was detached, which resulted in closure of the retinal breaks
      and reattachment of the retina in both cases. CONCLUSIONS: Cyanoacrylate creates
      a permanent closure of retinal breaks and may be useful in select cases of infant
      retinal detachment with posterior retinal breaks in which current available
      treatment failed or would fail.

PMID- 9564693
TI  - Timing of dexamethasone treatment in experimental Staphylococcus aureus
      endophthalmitis.
AB  - PURPOSE: This study sought to determine whether intravitreal dexamethasone with
      vancomycin preserves retinal function in eyes with experimental Staphylococcus
      aureus endophthalmitis better than intravitreal vancomycin alone. METHODS: Twenty
      four rabbits received intravitreal injections in both eyes with S. aureus. Right
      eyes were treated with intravitreal dexamethasone plus vancomycin and left eyes
      were treated with vancomycin alone at 24, 36, 48, or 72 hours after inoculation.
      Evaluation was performed by slit-lamp biomicroscopy, indirect ophthalmoscopy, and
      electroretinogram. Vitreous humor cultures and histopathologic examinations were
      performed on the eyes after the rabbits were killed. RESULTS: The combination of
      intravitreal dexamethasone and vancomycin resulted in significantly less
      inflammation than vancomycin alone at 24 and 36 hours after inoculation, but
      electroretinograms showed significantly better preservation only at 36 hours
      after bacterial inoculation. Viable bacteria were cultured from eyes treated 48
      and 72 hours after inoculation. CONCLUSION: Intravitreal dexamethasone was found
      to be beneficial by electroretinography when administered 36 hours after
      infection. In the authors' model, a single intravitreal injection of vancomycin
      with or without the addition of dexamethasone was insufficient to sterilize eyes
      48 and 72 hours after bacterial inoculation.

PMID- 9564694
TI  - Transplant of full-thickness embryonic rabbit retina using pars plana vitrectomy.
AB  - PURPOSE: To develop an improved surgical technique making full-thickness retinal
      transplant possible, thereby achieving a normal laminated transplant with minimal
      rosette formation. METHODS: A total of 23 rabbits underwent vitrectomy,
      retinotomy, and subsequent subretinal transplant of a complete embryonic
      neuroretina using a specially crafted glass cannula. Of the 23 animals, 15
      received a prenatal day 16 or 19 (E16 or E19) retina; the remaining eight
      received an E15 retina. The animals were followed from 10 to 35 days, and after
      this period, the transplants were sectioned and stained for light microscopy.
      RESULTS: In 11 of the 15 transplants with E16 or E19 donors, histology showed
      regions up to 1.8 mm of straight, correctly positioned transplants with layering
      corresponding to their age. The eight animals kept alive longest postoperatively,
      31 or 35 days, all showed normal retinal layers, including photoreceptor outer
      segments appositioned against the host retinal pigment epithelium. Tissue from
      the youngest donors (E15) yielded less well-organized transplants, indicating a
      critical stage in retinal embryogenesis before which transplant in this respect
      is less favorable. CONCLUSIONS: Our procedure makes it possible to transplant
      embryonic retina to the appropriate position adjacent to the host retinal pigment
      epithelium, keeping the transplant architecture intact. The transplants show good
      layering and well-developed photoreceptors abutting the retinal pigment
      epithelium.

PMID- 9564695
TI  - Progressive presumed choriocapillaris atrophy after surgery for age-related
      macular degeneration.
AB  - PURPOSE: The authors sought to evaluate the progression of presumed
      choriocapillaris atrophy after surgical excision of a subfoveal choroidal
      neovascular membrane (CNV) in an 80-year-old man with age-related macular
      degeneration. METHODS: The CNV was excised using a conventional three-port
      vitrectomy with subretinal dissection. The excised tissue was studied with light
      and electron microscopy. Preoperative and serial postoperative fluorescein
      angiograms (FA) and fundus photographs were obtained to study the dissection bed.
      RESULTS: Seven days after surgery, the FA showed hyperfluorescence in the area
      previously occupied by the CNV. Six weeks after surgery, this area showed retinal
      pigment epithelium (RPE) depigmentation, atrophy, or both on clinical
      examination, and the FA showed presumed choriocapillaris nonperfusion. Seven
      months after surgery, the area of the RPE depigmentation or atrophy and the
      corresponding area of presumed choriocapillaris nonperfusion had enlarged. The
      area of depigmentation or atrophy continued to enlarge for 1 year after surgery.
      Histologically, the excised CNV specimen disclosed RPE cells but no
      choriocapillaris. CONCLUSIONS: Presumed choriocapillaris nonperfusion after CNV
      excision may be due to RPE removal at surgery and may progress postoperatively.

PMID- 9564696
TI  - Quantitative analysis of foveal retinal thickness in diabetic retinopathy with
      the scanning retinal thickness analyzer.
AB  - PURPOSE: This study sought to measure foveal retinal thickness in patients with
      diabetic retinopathy and to investigate the relationship between foveal thickness
      and visual acuity, biomicroscopic findings, and angiographic features. METHODS: A
      commercial scanning retinal thickness analyzer was used to measure retinal
      thickness. A laser slit was projected onto the retina and scanned in 400
      milliseconds across the central area of the fundus. The image where the laser
      slit intersects with the retina was digitally recorded and analyzed. Retinal
      thickness was measured in 35 patients (35 eyes; patient age, 57 +/- 13 years)
      with diabetic retinopathy. Patients also were examined by fluorescein angiography
      and slit-lamp biomicroscopy to detect foveal thickening. RESULTS: Linear
      regression analysis indicated a significant correlation between foveal thickness
      and visual acuity (adjusted R2 = 0.72, P < 0.001). Foveal thickness was abnormal
      in 6 (100%) of 6 eyes in which foveal thickening was detected with slit-lamp
      biomicroscopy. Foveal thickness also was abnormal in 9 (31%) of 29 eyes that
      appeared normal by biomicroscopic examination. Foveal thickness was 136 +/- 65
      microns in 7 eyes without leakage, 175 +/- 35 microns in 13 eyes with
      questionable leakage, and 291 +/- 120 microns in 7 eyes with definite leakage (P
      = 0.0075). CONCLUSIONS: Retinal thickness analysis is shown to be more sensitive
      than slit-lamp biomicroscopy for detecting small changes in retinal thickness.
      Retinal thickness analysis may prove to be a useful, noninvasive modality for the
      development or regression of macular edema.

PMID- 9564697
TI  - Vitrectomy for diabetic retinopathy in patients undergoing hemodialysis for
      associated end-stage renal failure.
AB  - PURPOSE: Candidates for diabetic vitrectomy often have concurrent renal
      dysfunction and have undergone hemodialysis. The influence of hemodialysis on the
      surgical outcome of vitrectomy was investigated. METHODS: Vitrectomy was
      performed on 76 eyes with proliferative diabetic retinopathy in 66 patients with
      end-stage renal failure who had undergone hemodialysis. Follow-up was longer than
      1 year. RESULTS: No uncontrollable hemorrhage occurred either during or
      immediately after the surgery. Final visual acuity after surgery was the same as
      preoperative visual acuity in 31.5% of the eyes; improvement was seen in 60.5% of
      the eyes. A final visual acuity of 0.2 or better was observed in 57.6% of the
      eyes. Major postoperative complications included recurrent vitreous hemorrhage,
      rhegmatogenous retinal detachment, fibrin clot formation, neovascular glaucoma,
      flat anterior chamber, and a transient rise in intraocular pressure. CONCLUSION:
      Renal failure and hemodialysis do not appear to have a deteriorative influence on
      the outcome of vitrectomy for proliferative diabetic retinopathy. A flat anterior
      chamber seems to be a rare and perhaps unique postoperative complication of gas
      filled eyes in patients who have undergone hemodialysis.

PMID- 9564698
TI  - Conformance with the preferred practice pattern for diabetic eye care.
AB  - OBJECTIVE: To investigate conformance with a practice guideline in the eye care
      of patients with diabetes. METHODS: The care of 210 patients with diabetes seen
      in a multispecialty eye care setting was compared with the recommendations of the
      American Academy of Ophthalmology's Preferred Practice Pattern. Criteria measured
      included appropriate classification of stage of disease, follow-up intervals
      based on stage of disease, and initiation of appropriate laser treatment.
      RESULTS: The 210 patients whose charts were reviewed showed high levels of
      conformance with recommended care patterns. All patients were appropriately
      classified. From 91-100% of patients were seen within the recommended time
      intervals and received laser treatment when indicated. CONCLUSION: The American
      Academy of Ophthalmology's Preferred Practice Pattern can be easily
      operationalized into review criteria. Application of these review criteria to one
      multispecialty eye care setting shows evidence of high rates of conformance with
      recommended care.

PMID- 9564699
TI  - Findings of retinitis on gadolinium-enhanced turbo fluid-attenuated inversion
      recovery images.
AB  - PURPOSE: This study sought to determine the findings of retinal inflammation on
      gadolinium-enhanced turbo fluid-attenuated inversion recovery (tFLAIR) images.
      METHODS: Five patients with retinal abnormalities (acquired immunodeficiency
      syndrome complicated by cytomegalovirus retinitis, two patients; lymphoma
      complicated by Herpes zoster retinitis, one patient; and diabetic retinopathy,
      two patients) were identified on routine brain magnetic resonance imaging
      examinations performed with gadolinium-enhanced tFLAIR; five healthy subjects
      were retrospectively reviewed for comparison. Retinal signal features and
      thickness were evaluated comparing gadolinium-enhanced tFLAIR with turbo spin
      echo T2-weighted and spin-echo T1-weighted images with and without gadolinium.
      RESULTS: Abnormal retinal thickening and hyperintensity were most conspicuous on
      gadolinium-enhanced tFLAIR images. Unenhanced T1-weighted images failed to
      demonstrate any abnormalities. In the enhanced tFLAIR and T1-weighted images,
      retinal thickness greater than 1.2 mm was abnormal. Abnormal retinal contour and
      signal was most apparent on the tFLAIR images. CONCLUSIONS: Of the sequences
      studied, gadolinium-enhanced tFLAIR images were found to be the best in
      identifying incidental retinitis and diabetic retinopathy discovered on routine
      brain magnetic resonance imaging examinations.

PMID- 9564700
TI  - Use of an antimicrobial removal device in endophthalmitis cultures.
AB  - PURPOSE: This study sought to determine whether the use of an antimicrobial
      removal device (ARD) to process intraocular fluids increases microbial detection
      compared with conventional cultures. METHODS: The authors retrospectively
      reviewed all cases of endophthalmitis submitted to their laboratory from January
      1982 through December 1996. Aqueous or vitreous specimens or both that were
      cultured on conventional media (blood agar, chocolate agar, anaerobic blood agar,
      and thiol broth) and by ARD processing were included in the study. Specimens were
      inoculated into tubes with ARD for 5 to 10 minutes. The fluid was then withdrawn
      and cultured using conventional media; thioglycolate broth was added to the tube
      containing the resin beads. The conventional and ARD-processed cultures were
      incubated at 35 degrees C for at least 7 days. RESULTS: Of the 338
      endophthalmitis cultures processed using both conventional cultures and a
      parallel ARD, 166 (49.1%) yielded positive microbial growth on one or more media.
      Of the 166 culture-confirmed cases, 127 (76.5%) were positive in both the ARD
      processed and direct cultures, 17 (10.2%) were positive by conventional culture
      only, and 22 (13.3%) were positive by the ARD-processed sample alone (P = 0.52).
      The spectrum of microorganisms was similar among all culture groups. The
      detection of coagulase-negative staphylococci and micrococci by ARD alone was
      slightly better than detection by conventional culture only (P = 0.06). Of 93
      positive cultures from 179 patients in whom prior antibiotic use was documented,
      75 (80.6%) were positive by both methods, 8 (8.6%) by conventional cultures only,
      and 10 (10.8%) only by the ARD-processed specimen (P = 0.81). CONCLUSION: Use of
      an antimicrobial removal device does not significantly increase the microbial
      yield of endophthalmitis cultures compared with conventional culture techniques,
      whether or not antimicrobial therapy is being used.

PMID- 9564701
TI  - Diagnostic and therapeutic challenges.

PMID- 9564702
TI  - Bilateral retinal detachment associated with giant retinal tear after laser
      assisted in situ keratomileusis.

PMID- 9564703
TI  - Giant retinal tear in Usher syndrome type II: coincidence or association?

PMID- 9564704
TI  - Macular hole secondary to retrobulbar needle perforation.

PMID- 9564705
TI  - Choroidopathy in a patient with suspected systemic lupus erythematosus.

PMID- 9564706
TI  - Idiopathic juxtafoveal telangiectasia and positional visual disturbance.

PMID- 9564707
TI  - Peripheral retinal vascular occlusive disorder in a young patient with
      neurofibromatosis 1.

PMID- 9564708
TI  - Standard procedure performed to prevent migration of silicone oil to the anterior
      chamber in silicone oil-filled eyes that are also aphakic or pseudophakic.

PMID- 9564709
TI  - The fundus map: an advanced method of recording wide-field retinal pathology.

PMID- 9564710
TI  - Passive properties of human skeletal muscle during stretch maneuvers. A review.
AB  - Despite limited scientific knowledge, stretching of human skeletal muscle to
      improve flexibility is a widespread practice among athletes. This article reviews
      recent findings regarding passive properties of the hamstring muscle group during
      stretch based on a model that was developed which could synchronously and
      continuously measure passive hamstring resistance and electromyographic activity,
      while the velocity and angle of stretch was controlled. Resistance to stretch was
      defined as passive torque (Nm) offered by the hamstring muscle group during
      passive knee extension using an isokinetic dynamometer with a modified thigh pad.
      To simulate a clinical static stretch, the knee was passively extended to a pre
      determined final position (0.0875 rad/s, dynamic phase) where it remained
      stationary for 90 s (static phase). Alternatively, the knee was extended to the
      point of discomfort (stretch tolerance). From the torque-angle curve of the
      dynamic phase of the static stretch, and in the stretch tolerance protocol,
      passive energy and stiffness were calculated. Torque decline in the static phase
      was considered to represent viscoelastic stress relaxation. Using the model,
      studies were conducted which demonstrated that a single static stretch resulted
      in a 30% viscoelastic stress relaxation. With repeated stretches muscle stiffness
      declined, but returned to baseline values within 1 h. Long-term stretching (3
      weeks) increased joint range of motion as a result of a change in stretch
      tolerance rather than in the passive properties. Strength training resulted in
      increased muscle stiffness, which was unaffected by daily stretching. The
      effectiveness of different stretching techniques was attributed to a change in
      stretch tolerance rather than passive properties. Inflexible and older subjects
      have increased muscle stiffness, but a lower stretch tolerance compared to
      subjects with normal flexibility and younger subjects, respectively. Although far
      from all questions regarding the passive properties of humans skeletal muscle
      have been answered in these studies, the measurement technique permitted some
      initial important examinations of vicoelastic behavior of human skeletal muscle.

PMID- 9564711
TI  - Rifle-balancing in precision shooting: behavioral aspects and psychophysiological
      implication.
AB  - This study investigated sharpshooters' strategies to control their rifle
      stability during the aiming period. Six elite and six pre-elite shooters
      completed a simulated realistic shooting task (laser rifle), and their
      performance was evaluated from behavioral and psychophysiological perspectives.
      The analysis of the rifle's barrel movement, indexing the shooter's behavioral
      performance, supported the view that rifle-balancing is an essential determinant
      of superior shooting performance. The psychophysiological data, i.e. the brain
      slow potentials, suggested that the shooters applied different rifle-hold
      strategies; the elite shooters concentrated primarily on achieving a stable rifle
      position using psychomotor regulation, whereas the pre-elite shooters were more
      reliant on the visual-spatial processing. The present study has implications for
      the understanding of psychological aspects in competitive precision shooting, as
      well as for the evaluation of the functional significance of the electrocortical
      slow potentials in shooting-like closed-skill sports.

PMID- 9564712
TI  - Cutaneous blood flow rate in areas with and without arteriovenous anastomoses
      during exercise.
AB  - In 10 healthy subjects, skin blood flow rate was measured in the thumb pulp by
      the heat-washout method, and in the skin fold between the thumb and the
      forefinger by the 133Xe-washout method. The former but not the latter skin area
      contains arteriovenous anastomoses (AVAs). In response to 10 min moderate bicycle
      exercise, an instantaneous decrease in flow was seen in the thumb pulp followed
      after about 4.6 min by an increase to resting levels. Blood flow in the skin fold
      remained constant. The results indicate that the initial reduction in blood flow
      rate and later increase observed in the finger at the onset of moderate exercise
      take place in the AVAs and not in the capillaries.

PMID- 9564714
TI  - Lactate/H+ transport in skeletal muscle from spinal-cord-injured patients.
AB  - In order to evaluate the effect of prolonged muscle inactivity on sarcolemmal
      lactate/H+ transport in humans, the lactate/H+ transport capacity was determined
      in the thigh muscle of spinal-cord-injured (SCI) individuals. The lactate
      transport rate was measured in sarcolemmal giant vesicles produced by collagenase
      treatment of muscle biopsies obtained from the vastus lateralis muscle. Six SCI
      subjects with total loss of motor and sensory functions of their lower limbs
      participated in the study. The duration of the injury ranged from 2 to 15 years.
      The total lactate transport rate in the muscle of SCI patients was 46.5 +/- 2.6
      pmol.cm-2.s-1 (mean +/- SEM), which corresponds to a 17% lower (P < 0.05)
      transport rate than that found in healthy, untrained subjects. The estimated
      carrier-mediated lactate/H+ transport capacity was approximately 26% lower in the
      SCI patients than in healthy, untrained subjects. The observed muscle lactate/H+
      transport capacity of SCI individuals is in accordance with a positive
      correlation between the capacity of the lactate/H+ transporters and the
      percentage occurrence of slow-twitch fibres in a muscle, although there seems to
      be a wide range of transport capacities within each fibre type. The present
      results show that the sarcolemmal lactate/H+ transport capacity is lower in SCI
      individuals than in normally physically active subjects, which indicates that
      prolonged muscle inactivity reduces the lactate/H+ transport capacity of human
      muscle.

PMID- 9564713
TI  - Aspects of leukocyte function and the complement system following aerobic
      exercise in young female gymnasts.
AB  - Recent studies have reported reduced immunity in trained athletes. Scant
      information exists on changes in the immune function among trained children. The
      purpose of this study was to assess the effect of aerobic exercise on the
      phagocytic process of neutrophils and the complement system in young athletes.
      Subjects included prepubertal elite female gymnasts (n = 7) and untrained girls
      (n = 6) aged 10-12 years. Venous blood was withdrawn before, immediately post and
      24 h following a 20-min run at a heart rate of 170-180 beats.min-1. Neutrophil
      random migration, chemotactic activity, bactericidal function and PMA/FMLP
      stimulated superoxide anion release as well as various complement components were
      assessed. Net chemotaxis was found reduced (P < 0.05) 24 h following exercise (58
      +/- 11 vs. 36 +/- 11 cells/field in gymnasts and 47 +/- 7 vs. 42 +/- 8
      cells/field in untrained girls pre- and 24 h post-exercise, respectively). The
      basal values, as well as post-exercise values of bactericidal activity were lower
      (P < 0.05) in gymnasts as compared with the control group (0.8 +/- 0.3, 0.8 +/-
      0.2 and 0.8 +/- 0.1 log decrease of colonies in gymnasts at pre-, immediately
      post-, and 24 h post-exercise, respectively and 1.1 +/- 0.1, 1.1 +/- 0.1 and 1.0
      +/- 0.2 log decrease of colonies in controls, respectively). No significant
      effect on the bactericidal activity was observed in either group following
      exercise. The addition of homologous sera did not correct the bactericidal
      activity. PMA-stimulated superoxide anion release decreased (P < 0.05) among
      gymnasts immediately following exercise (5.7 +/- 0.4 vs. 4.4 +/- 1.0 mmol
      O2/10(6) PMN.min) and remained low 24 h later. The same trend was observed in
      FMLP-stimulated neutrophils but the data were not significant. Significantly
      decreased levels (P < 0.05) of the early complement components (C1Q, C1R) were
      also found following exercise (1.34 +/- 0.64 vs. 1.27 +/- 0.28 and 1.09 +/- 0.07
      vs. 1.02 +/- 0.06 pre- and post-exercise in gymnasts and untrained,
      respectively). Furthermore, consistently lower C2 and C3 were observed in
      gymnasts compared with controls. Neutrophil dysfunction as well as impairment of
      the complement system seem to occur following exercise.

PMID- 9564715
TI  - Regional body composition determined by dual-energy X-ray absorptiometry.
      Relation to training, sex hormones, and serum lipids in male long-distance
      runners.
AB  - This study investigated the regional distribution of fatty and lean tissue in
      long-distance runners, and the relation to training, sex hormones, and serum
      lipids. One hundred and twenty lean men (22 elite, 86 recreational runners and 12
      non-running controls) aged 32 +/- 8.1 years (mean +/- SD) participated. Body
      composition (adipose and lean tissue) was measured by dual-energy x-ray
      absorptiometry in the total body and in the abdomen, the arms and the legs.
      Regional and total body fat correlated inversely with the performance at an
      incremental treadmill exercise test (-0.61 < r < -0.52, P < 0.0001), and the fat
      percentage in the abdomen and in the legs was 42% and 36% lower in the elite
      runners in comparison with the non-running controls. Sex hormonal status and
      serum lipids were unrelated to training. After multiple regression analysis the
      most significant determinant of the fat percentage in the legs was the weekly
      distance run (partial r = -0.40, P < 0.0001), whereas in the abdominal region the
      free testosterone index also contributed strongly (partial r = 0.39, P < 0.0001).
      In conclusion, long-distance runners had very low amounts of fatty tissue in the
      abdomen and in the extremities, and the fat percentages in the abdomen and in the
      legs were associated with both the training intensity and androgenic activity.
      Since the abdominal fatty tissue is a significant risk factor for cardiovascular
      disease, running may have a positive impact on the long-term risk.

PMID- 9564716
TI  - Associations between central obesity and indexes of hemostatic, carbohydrate and
      lipid metabolism. Results of a 1-year intervention from the Oslo Diet and
      Exercise Study.
AB  - The relationships of central obesity and physical fitness to indexes of
      hemostatic, lipid and glucose metabolism both at baseline and after 1 year of
      diet and exercise intervention were examined in 209 sedentary middle-aged men and
      women with increased coronary risk factor levels. Central obesity was measured as
      either waist circumference or waist/hip ratio. Maximal oxygen uptake was used as
      a measure of physical fitness. The cross-sectional results show that there were
      significant correlations between waist circumference and euglobuline clot lysis
      time (r = 0.23), factor VII (r = 0.16), glucose and insulin before and after 1 h
      glucose load (r ranging from 0.32 to 0.50). The 1-year intervention gave the
      following associations between changes in waist circumference and changes in:
      euglobuline clot lysis time (r = 0.27), factor VII (r = 0.19), carbohydrate
      variables and lipids (magnitude of r ranging from 0.19 to 0.43). Also the other
      indexes of obesity and physical fitness showed significant correlations to
      indexes of hemostatic, lipid and glucose variables, both cross-sectionally and
      for changes after the 1-year intervention. The associations between changes in
      central obesity and changes in indexes of hemostatic, carbohydrate and lipids
      were generally stronger during 1 year of diet and exercise intervention than
      those found at baseline. Multiple regression analyses with waist circumference,
      waist/hip ratio, percent body fat and Vo2 max as independent variables and
      indexes of hemostatic, carbohydrate and lipid metabolism as dependent variables
      showed that waist circumference was a significant predictor for indexes of the
      hemostatic, carbohydrate and lipid metabolism, mostly independent of physical
      fitness. The cross-sectional and 1-year change results support each other and
      therefore underscore the importance of abdominal obesity as an important risk
      factor for cardiovascular disease.

PMID- 9564717
TI  - A study of sports-related mandibular angle fracture: relation to the position of
      the third molars.
AB  - Mandibular angle fractures have been considered attributable to the presence of
      unerupted third molars. We examined the relationship between the incidence of
      sports-related mandibular angle fractures and the presence of a mandibular third
      molar with emphasis on the position of the third molar. The incidence of angle
      fracture was significantly higher in the sports-related injury group than in the
      group with fracture due to other causes (P < 0.05). The incidence of angle
      fracture in the athletes with higher impaction scores was significantly higher
      than that in the subjects with higher scores who did not have sports-related
      fractures (P < 0.05). The percentage of rugby athletes with third molars was
      significantly higher than that of those without third molars (P < 0.001), and a
      high proportion of young athletes (89.5%) was considered to belong to a potential
      high-risk group for angle fractures. Our findings suggest that mandibular angle
      fractures are influenced by the presence and characteristics of the third molar
      in sports-related injuries.

PMID- 9564718
TI  - The relationship between achievement goal profile groups and perceptions of
      motivational climates in sport.
AB  - The purpose of the present study was to expand on previous research that has
      found compatibility between individuals' views on achievement and the type of
      achievement that was promoted in the sport environment they belonged to. However,
      this line of research has ignored the fact that the two main goal orientations
      are largely independent and that their impact in combination is often different
      from their effects examined separately. The present study, therefore, examined
      which combinations of goal orientations are compatible with perceptions of
      mastery and performance climates in a sample of 146 British university students.
      With regard to mastery climate, the analysis showed that the critical factor was
      the degree of task orientation since those with high scores in this factor
      (irrespective of the degree of their ego orientation) perceived the climate as
      more mastery-oriented than those with low scores in task orientation. This was
      substantiated by the large differences in effect sizes between the high- and low
      task groups. As far as performance climate was concerned, the most negative
      perceptions of climate were held by those who were rated both low in task
      orientation and high in ego orientation. A general inference from these results
      is that high task orientation is motivationally adaptive, whereas high ego
      orientation is not motivationally detrimental as long as it is accompanied by a
      high task orientation. These findings are in contrast with previous suggestions
      that have called for the enhancement of task orientation with the concurrent
      suppression of ego orientation. Our results are, however, consonant with studies
      which have employed a goal profiles analysis in sport and in physical education,
      and with empirical evidence from real sport settings.

PMID- 9564719
TI  - Rapid decrease of endemic gonorrhea in Finland.
AB  - OBJECTIVES: The incidence of gonorrhea has decreased in several European
      countries while a recent epidemic has occurred in Russia and the Baltic
      countries. In 1990, Finland had a higher gonorrhea incidence than the other
      Nordic countries. Therefore we studied prospectively the epidemiology of
      gonorrhea with special reference to the endemic or imported source of infection.
      STUDY DESIGN: The study included three gonorrhea patient series from STD clinics
      in Helsinki in 1990 to 1995. Each series covered a 12-month period. Case controls
      with Chlamydia trachomatis infection were included. Demographic and
      epidemiological findings, including source partner profiles, were analyzed.
      RESULTS: Gonorrhea decreased rapidly during the study period. In 1990 to 1991,
      there were 490 patients (3.3% of all patient visits); in 1992 to 1993, 162
      (1.3%); and in 1994 to 1995, only 92 patients (0.9%) with gonorrhea. The change
      in the prevalence was highly significant (p < 0.0001) and was entirely because of
      the decreased number of endemic infections. The rate of imported gonorrhea
      remained constant with 50 to 60 patients, although traveling had increased
      markedly to Russia and Estonia where the incidence of gonorrhea was very high.
      Thirty-one percent of the patients with endemic gonorrhea but only 14% with
      imported gonorrhea (p < 0.0001) had a concomitant C. trachomatis infection. The
      prevalence of chlamydia decreased from 10.2 to 8.1% (p < 0.001), but in contrast
      to gonorrhea the source of infection was mainly endemic (89% to 97%) during the
      whole study period. The patients with gonorrhea were older and had a higher
      frequency of casual source partners than those with chlamydia. Overall, from 80%
      to 74%) of the men and from 48% to 33% of the women had contracted infection from
      a casual partner. CONCLUSION: The present study documented a rapid decrease of
      endemic gonorrhea in Finland, whereas the rate of imported gonorrhea remained
      constant. Demographic findings or source partner profiles of patients with
      gonorrhea or chlamydia gave no obvious explanation for the rapid decline of
      endemic gonorrhea, which is in sharp contrast to C. trachomatis infection.

PMID- 9564720
TI  - The high-risk sexual practices of crack-smoking sex workers recruited from the
      streets of three American cities. The Multicenter Crack Cocaine and HIV Infection
      Study Team.
AB  - BACKGROUND AND OBJECTIVES: Small ethnographic and clinic-based studies indicate
      that crack-smoking sex workers are at high risk for human immunodeficiency virus
      (HIV) and sexually transmitted diseases (STD). STUDY GOALS: To examine the
      prevalence of risky sexual behaviors and HIV and STD in a large sample of street
      recruited crack-smoking sex workers. STUDY DESIGN: From 1991 to 1992, 419 crack
      smoking sex workers were recruited from urban neighborhoods, interviewed, and
      serologically tested. RESULTS: Many female and male sex workers reported sex with
      injectors (30% to 41%) or HIV-infected persons (8% to 19%), past STD (73% to
      93%), and inconsistent condom use (> 50% for all types of sex). Sex workers who
      worked in crack houses or vacant lots, were paid with crack, or injected drugs
      had the riskiest sex practices. Most sex workers initiated sex work before they
      first smoked crack. More than 25% were infected with HIV (27.9%), syphilis
      (37.5%), or herpes simplex virus type 2 (66.8%). CONCLUSIONS: Interventions to
      prevent HIV/STD transmission among crack-smoking sex workers are urgently needed.

PMID- 9564721
TI  - The value of workplace versus income in determining HIV status and other STDs
      among a sample of Spanish sex workers.

PMID- 9564722
TI  - Clinico-epidemiologic features of granuloma inguinale in the era of acquired
      immune deficiency syndrome.
AB  - BACKGROUND AND OBJECTIVES: Granuloma Inguinale (GI) is an endemic sexually
      transmitted disease (STD) in India. With increasing prevalence of human
      immunodeficiency virus (HIV) among patients with STD at a clinic in Mumbai, a
      study was conducted to determine clinico-epidemiologic features of GI and HIV.
      GOAL: To determine possible interaction between GI and HIV. STUDY DESIGN:
      Prospective follow-up of 21 consecutive cases (GI in HIV-seropositive
      individuals) and 29 controls (GI in HIV-seronegative individuals) to determine
      time to heal. All cases and controls received a standard treatment regimen of
      erythromycin, 2 g po daily, under supervision until healing occurred. RESULTS:
      Although GI ulcers at recruitment were not significantly larger among HIV
      seropositive individuals as compared with those seen among HIV-seronegative
      individuals (mean size 4.4 cm2 vs. 3.6 sq2; odds ratio [OR] 1.22, confidence
      interval [CI] .95, 0.63, 2.40; p = 0.52), the former took longer time to heal
      completely (mean 25.7 days vs. 16.8 days; OR 1.82, CI .95, 0.99, 3.36; p = 0.03)
      and tended to produce greater tissue destruction (as included in results).
      CONCLUSION: These findings are important because slow-healing GI ulcers with
      underlying HIV infection, which may be caused by their interaction, will lead to
      increased transmission of both the infections.

PMID- 9564723
TI  - Screening for chlamydial infection. A model program based on prevalence.
AB  - BACKGROUND: Chlamydial infection accounts for substantial health care costs. The
      high frequency of asymptomatic infections necessitates screening to detect
      affected persons. Selective screening using risk assessment criteria attempts to
      target limited resources to women at increased risk. However, most risk
      assessment criteria have not accounted for prevalence of infection. OBJECTIVES:
      To describe currently available screening options, to demonstrate the
      relationship between prevalence and probability of infection, and to propose a
      model program incorporating clinic prevalence in selective screening decisions.
      STUDY DESIGN: A simple model demonstrating the relationship between clinic
      prevalence, a risk score based on risk assessment, and probability of infection
      was developed using basic clinical epidemiological principles. RESULTS: The
      probability of infection can be estimated from the clinic prevalence and risk
      score. If the estimated probability of infection exceeds previously established
      test thresholds, laboratory testing is warranted. As the clinic prevalence
      increases, the risk score necessary to justify laboratory testing decreases.
      Thus, the cutoffs for risk assessment criteria should be adjusted to account for
      clinic prevalence. In the proposed model program, the availability of resources,
      such as the number of tests available to a screening program, can be accommodated
      by appropriate adjustment of thresholds for laboratory testing. CONCLUSION: The
      prevalence-based chlamydial screening program may provide a pragmatic strategy
      for areas with limited resources.

PMID- 9564724
TI  - The acceptability of oral fluid testing for HIV antibodies. A pilot study in gay
      bars in a predominantly rural state.
AB  - BACKGROUND: One barrier for individuals desiring human immunodeficiency virus
      (HIV) antibody testing has been the lack of alternatives to blood HIV testing.
      Oral fluid HIV testing provides another testing option. OBJECTIVES: To evaluate
      the acceptability of oral fluid testing for HIV antibodies in a gay bar outreach
      setting. STUDY DESIGN: This pilot study was conducted using the HIV Risk Behavior
      Survey (HRBS) and OraSure acceptability survey in gay bars in Columbia, South
      Carolina during July and August, 1997. RESULTS: Of the 118 HRBS participants, 54%
      agreed to take the oral fluid test with 6% testing positive. A majority (91%) of
      participants felt comfortable with the oral HIV antibody testing in gay bars.
      Also, 21.8% of individuals in the OraSure study were tested for the first time.
      CONCLUSION: This study indicates that oral fluid testing for HIV antibodies in an
      outreach setting is acceptable and effective in reaching individuals who do not
      usually access traditional testing sites.

PMID- 9564725
TI  - Heterosexual intercourse in a French prison.

PMID- 9564726
TI  - Emphasizing infectious syphilis partner notification.

PMID- 9564727
TI  - Hepatitis C transmission and the underreporting of stigmatized behaviors.

PMID- 9564729
TI  - Awareness of and experience with the female condom among patients attending STD
      clinics.

PMID- 9564730
TI  - Naphthoquinone metabolites of the fungi.
AB  - Structures and physico-chemical properties of 100 naphthoquinone metabolites
      produced by filamentous fungi are reviewed. The conditions of pigment formation,
      biogenesis and the mechanism of biosynthesis of pigments by fungi are described.
      Sixty-three fungi cultures able to produce naphthoquinone are listed. The
      biological activities of the main pigments and the mechanism of fungal resistance
      to their own metabolites are described. The physiological role of the
      naphthoquinones in producers is discussed.

PMID- 9564731
TI  - Enolic iridolactone and other iridoids from Alberta magna.
AB  - From fresh leaves of Alberta magna two new iridoids and a known cyclopentene
      dialdehyde have been identified. One of the new compounds has the less-common
      irido-lactone structure and has an enolic hydrogen on C-4. Two of the compounds
      show short term mosquito-repellent effects.

PMID- 9564732
TI  - Biotransformation of linalool to furanoid and pyranoid linalool oxides by
      Aspergillus niger.
AB  - Biotransformation of (+/-)-linalool with submerged shaking cultures of
      Aspergillus niger, particularly A. niger ATCC 9142, yielded a mixture of cis- and
      trans-furanoid linalool oxide (yield 15-24%) and cis- and trans-pyranoid linalool
      oxide (yield 5-9%). Biotransformation of (R)-(-)-linalool with the same strain
      yielded almost pure trans-furanoid and trans-pyranoid linalool oxide (ee > 95).
      These conversions were purely biocatalytic, since in acidified water (pH < 3.5)
      almost 50% linalool was recovered unchanged, the rest was lost by evaporation.
      The biotransformation was also carried out with growing surface cultures.

PMID- 9564734
TI  - [Comprehensive geriatric assessment].

PMID- 9564733
TI  - Acetogenins from seeds of Annona reticulata.
AB  - Chromatography of an ethyl acetate extract of seeds of Annona reticulata led to
      the isolation of a new cytotoxic gamma-lactone acetogenin, cis-/trans
      isomurisolenin, along with six known cytotoxic acetogenins, annoreticuin,
      annoreticuin-9-one, bullatacin, squamocin, cis-/trans-bullatacinone and cis
      /trans-murisolinone. Structures of these compounds were established by means of
      mass and related spectral experiments. Some of the compounds isolated, showed
      potent cytotoxicities against Hep. 2,2,15, Hep. G2, KB and CCM2, four cancer cell
      lines.

PMID- 9564735
TI  - [Recent progress in telomere/telomerase research].

PMID- 9564736
TI  - [Geriatrics and neurology].

PMID- 9564738
TI  - [Relationship between ultrastructure of myeloma cells and clinical features in
      elderly patients with multiple myeloma].
AB  - The relationship between the ultrastructure of plasma cells and clinical features
      was analyzed in 54 patients with multiple myeloma: 20 elderly patients (9,8 and 3
      cases of IgG, IgA and BJP types, respectively; 5,3 and 12 cases in clinical stage
      I, II and III, respectively) and 34 young patients (16, 10, 1 and 7 cases of IgG,
      IgA, IgD and BJP types, respectively; 5, 10 and 19 cases in clinical stage I, II
      and III, respectively). Five-year survival rates of the elderly and young groups
      were 41.5 and 60.5%, respectively, though the difference of both survival curves
      was not significant. Response rates of initial therapy in the elderly and young
      groups were 55 and 56%, respectively (not significant). The number of patients
      presenting disarrangement of organelles was significantly larger in the elderly
      group, but those presenting other abnormal structures were equal between both
      groups. The ratios of dense body, intramitochondrial granules and multilamellar
      body in bone marrow plasma cells were significantly higher in nonresponders than
      in responders of the elderly group. The ratios of disarrangement of organelles,
      single sac loop-like structure and intramitochondrial granules in bone marrow
      plasma cells were significantly higher in nonresponders than in responders of the
      young group. It is suggested that the ultrastructure of plasma cells in multiple
      myeloma differs between elderly and young patients and is useful in predicting
      the respective clinical features, although drug responses and survival curves do
      not show a significant difference.

PMID- 9564737
TI  - [Influence of kyphosis on the age-related decline in pulmonary function].
AB  - To examine the influence of kyphosis on pulmonary function in the elderly, 300
      consecutive healthy subjects (aged 20-94 years old) were evaluated using
      pulmonary function tests (TLC, VC, FEV1, RV) and static maximal pressures (PImax
      and PEmax). Kyphosis of the thoracic bones was measured at Cobb's angle. VC,
      FEV1. PImax and PEmax showed a significant age-dependent decline. Cobb's angle
      had a positive relationship with age and was negatively correlated with TLC, VC,
      FEV1 and PImax. Further, RV/TLC strongly correlated with Cobb's angle and PImax.
      Stepwise regression analysis revealed that the kyphotic angle was an independent
      determinant for PImax and RV/TLC. These results indicate that kyphosis
      significantly affects lung volume and maximal inspiratory pressure in the elderly
      and those affected should have careful assessment of their pulmonary function and
      respiratory pressures.

PMID- 9564739
TI  - [Effect of bisoprolol, a beta 1-selective beta-blocker, on lipid and glucose
      metabolism and quality of life in elderly patients with essential hypertension].
AB  - The present study investigated the effect of bisoprolol, a beta 1-selective beta
      blocker without intrinsic sympathomimetic activity (ISA), on lipid and glucose
      metabolism and quality of life (QOL) in elderly patients with essential
      hypertention. Bisoprolol at doses of 5-10 mg was administered once daily for 12
      weeks to 60 non-elderly and 21 elderly outpatients with mild to moderate
      essential hypertension. In both groups bisoprolol significantly decreased both
      systolic and diastolic blood pressures and significantly reduced pulse rates to
      the same extent. The levels of serum cholesterol, HDL-cholesterol and
      triglyceride, and the response of plasma glucose and insulin to 75 g oral glucose
      load, were not changed in either group by the bisoprolol treatment. Bisoprolol
      significantly improved QOL in both groups. Bradycardia, a side effect
      attributable to bisoprolol, was noted in only one patient in the elderly group.
      These results suggest that bisoprolol is a safe and useful antihypertensive drug
      in elderly and non-elderly patients with essential hypertension.

PMID- 9564740
TI  - [Clinical study of elderly patients with non-Hodgkin's lymphoma arising in the
      thyroid].
AB  - The study group comprised 10 patients who were referred between 1992 and 1996
      with non-Hodgkin's lymphoma arising in the thyroid gland. There were three men
      and seven women, with a median age of 75 years, and seven of the group had a
      history of Hashimoto's disease. All 10 patients had hypothyroidism; anti
      microsomal antibody was positive in six. The lymphoma was of the diffuse type in
      all patients (B cell, 9; T cell, 1). Five patients had stage I and five had stage
      II. Generally, four courses of COP-BLAM therapy were given, followed by
      radiotherapy (30 Gy). Complete remission was achieved in all patients, and they
      remained alive and disease-free for a median period of 40 months. Ultrasonography
      revealed diffuse, an-or hypoechoic confluent nodules, and there was
      intensification of the posterior acoustic enhancement in most patients. With
      early diagnosis non-Hodgkin's lymphoma arising in the thyroid of elderly
      patients, mainly women, can be cured with chemotherapy and radiotherapy.

PMID- 9564741
TI  - [Basic activities of daily living of elderly inpatients].
AB  - Basic activities of daily living (ADL) together with communication ability
      (visual, auditory and speech) and frequency of bedside visits by a nurse were
      assessed in 672 elderly inpatients staying on a certain day in Tokyo Metropolitan
      Geriatric hospital, which is a specialized general hospital for geriatrics but
      not a long-stay chronic care hospital. Diseases were divided into seven groups:
      neurological (N), circulatory (C), respiratory (P), bone and joint (B), malignant
      (M), dementia (D) and other disorders (O). The purpose of the study was to
      clarify the functional state of elderly inpatients and to correlate the Barthel
      indices (BAI) of ADL with disease group, communication ability, frequency of
      bedside visits, age and gender. Multivariate analysis revealed a significant
      association of BAI with frequency of bedside visits by a nurse, communication
      ability, disease group and age. Scores in patients of N and D groups were
      significantly decreased compared with other diseases in many items composing the
      BADL. Patients of B group showed significantly decreased scores in mobility,
      stairs and bathing, while patients of P group had decreased scores for stairs and
      bathing. Bathing and stairs were the most difficult activities in the BADL. BAI
      were linearly correlated with transfer. When independence of feeding was lost,
      the patients were almost totally dependent. The functional state should be
      assessed in geriatric inpatients where the quality of life of the patients must
      take priority over other considerations in the decision making for interventions.
      The BAI is easy to use and reliable and is probably a suitable tool evaluating
      the BADL in a comprehensive geriatric assessment.

PMID- 9564742
TI  - [An elderly patient with bleeding from the alimentary tract caused by aberrant
      pancreas of the small intestine].
AB  - A 71-year-old woman was admitted to hospital because of malaise and bloody stool.
      Laboratory findings consistently showed anemia (Hb 9.2 g/dl) and occult blood in
      the stool. Although barium series and endoscopy of the upper and lower intestinal
      tructs were carried out, there was no evidence of bleeding from the
      gastrointestinal tract 99mTcO4- scintigraphy, which was performed to exclude
      bleeding from Meckel's diverticulum, also did not locate a significant lesion.
      Angiographic imaging of the superior mesenteric arteries (SMA) was performed to
      exclude lesions such as small intestine tumors with extraluminal growth and
      vascular abnormalities such as A-V malformation and it revealed the round
      encasement of arteries in the peripheral SMA region, strongly suggestive of a
      small intestine tumor. Surgery was performed and an extraluminally protruding
      tumor was found in the small intestine. The excised tumor was 4 x 3 x 3.5 cm in
      size, are was diagnosed histologically as aberrant pancreas. The postoperative
      laboratory findings showed that the anemia had improved and occult blood was not
      detected in the stools. Although aberrant pancreas of the small intestine is a
      common benign tumor, it is a very unusual cause of bleeding from the alimentary
      tract.

PMID- 9564743
TI  - Cerebral event-related potentials associated with selective attention to color:
      developmental changes from childhood to adulthood.
AB  - Event-related potentials were recorded from 80 participants ranging in age from 7
      to 24 years while they attended selectively to stimuli with a specified color
      (red or blue) in an attempt to detect the occurrence of target stimuli. Color
      attention effects were identified as frontal selection positivity (FSP; 140-275
      ms), selection negativity (SN; 150-300 ms), and N2b (200-450 ms), whereas target
      detection was reflected in P3b (300-700 ms). There were age-related decreases in
      the latencies of FSP, N2b, and P3b that paralleled decreases in reaction time and
      error rates. Also, the SN amplitude increased with advancing age, whereas both
      N2b and P3b showed changes in scalp topography. These results represent
      neurophysiological evidence that the efficiency of visual selective processes
      increases during childhood and adolescence. Developmental growth may take place
      at both relatively early and late levels of visual selective information
      processing.

PMID- 9564744
TI  - Neurophysiological evidence for visual perceptual categorization of words and
      faces within 150 ms.
AB  - The nature and early time course of the initial processing differences between
      visually matched linguistic and nonlinguistic images were studied with event
      related potentials (ERPs). The first effect began at 90 ms when ERPs to written
      words diverged from other objects, including faces. By 125 ms, ERPs to words and
      faces were more positive than those to other objects, effects identified with the
      P150. The amplitude and scalp distribution of P150s to words and faces were
      similar. The P150 seemed to be elicited selectively by images resembling any well
      learned category of visual patterns. We propose that (a) visual perceptual
      categorization based on long-term experience begins by 125 ms, (b) P150 amplitude
      varies with the cumulative experience people have discriminating among instances
      of specific categories of visual objects (e.g., words, faces), and (c) the P150
      is a scalp reflection of letterstring and face intracranial ERPs in posterior
      fusiform gyrus.

PMID- 9564746
TI  - Selective attention and N400 attenuation with spoken word repetition.
AB  - In two experiments, event-related brain potential were recorded to word pairs
      simultaneously presented to both ears, with instructions to attend to one ear and
      detect occasional nonwords in that ear. This attentional manipulation yielded
      four patterns of word repetition on successive trials: first and second
      presentations attended (AA), both unattended (UU), and across ears (AU and UA). A
      prominent attenuation of N400 due to immediate repetition of words was observed
      on AA trials. However, when first presentations were ignored on UU and UA trials,
      no repetition effect was obtained. These findings indicate that the repetition
      effect on N400 depends on attentional processing of first presentations.

PMID- 9564745
TI  - Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic and
      cold pressor.
AB  - Secretory immunoglobulin A (sIgA) in saliva and cardiovascular reactions to
      mental arithmetic and cold pressor tasks were recorded in 16 healthy young men on
      two sessions, 4 weeks apart. Both tasks elicited significant increases in sIgA
      secretion rate, reflecting increases in both salivary volume and sIgA
      concentration. Whereas mental arithmetic elicited a mixed pattern of alpha- and
      beta-adrenergic cardiovascular reactions, the pattern of reactions to cold
      pressor was predominantly alpha-adrenergic. Task levels of sIgA secretion rate,
      sIgA concentration, and saliva volume showed moderate to high test-retest
      reliability (r = .52-.83), although test-retest correlations were less impressive
      for change scores (r = -.19-.53). The pattern of correlations between change in
      sIgA secretion rate and cardiovascular reactivity variables was inconsistent.

PMID- 9564747
TI  - Topography of CNV and PINV in schizotypal personality.
AB  - The topography of the postimperative negative variation (PINV) was analyzed in
      participants with high and low scores on the German version of the Schizotypal
      Personality Questionnaire. Scalp amplitude and Laplacian maps of the terminal
      contingent negative variation (tCNV) and PINV and the time course of the PINV
      were compared between the two groups. CNV and PINV were induced with a delayed
      matching-to-sample task, in which the pattern of the imperative stimulus was
      either clearly or ambiguous matched to one of the two diamonds simultaneously
      presented as a warning stimulus 4.0 s earlier. Electroencephalograms were
      recorded with a DC amplifier (32 channels). Negativity increased from tCNV to
      PINV, especially at frontal sites, and the PINV was larger under ambiguous than
      under clear matching conditions. Low-scoring participants showed a right-sided
      predominance of the PINV, which was absent in high-scoring participants. These
      results resemble differences in the topography of the PINV between healthy
      control participants and those with schizophrenia under identical experimental
      conditions and suggest functional differences between tCNV and PINV.

PMID- 9564748
TI  - Magnetoencephalographic recordings demonstrate attentional modulation of mismatch
      related neural activity in human auditory cortex.
AB  - It is widely agreed that the negative brain potential elicited at 150-200 ms by a
      deviant, less intense sound in a repetitive series can be modulated by attention.
      To investigate whether this modulation represents a genuine attention effect on
      the mismatch negativity (MMN) arising from auditory cortex or attention-related
      activity from another brain region, we recorded both the MMN and the mismatch
      magnetic field (MMF) elicited by such deviants in a dichotic listening task.
      Deviant tones in the attended ear elicited a sizable MMF that was well modeled as
      a dipolar source in auditory cortex. Both the MMN and MMF to unattended-ear
      deviants were highly attenuated. These findings support the view that the MMN/MMF
      elicited in auditory cortex by intensity deviants, and thus the underlying
      feature-analysis and mismatch-detection processes, are not strongly automatic but
      rather can be gated or suppressed if attention is strongly focused elsewhere.

PMID- 9564749
TI  - Event-related potentials and serial position effects in a visual probe
      recognition task.
AB  - In two experiments, we explored the utility of using event-related brain
      potentials (ERPs) evoked during picture recognition to examine the cognitive and
      neural processes underlying primacy and recency effects. Each experiment
      consisted of 210 trials in which a recognition probe followed a 12-picture
      sequence (105 match and 105 nonmatch trials). The 105 match-probe trials
      consisted of 35 trials in which the probe matched a prime memory set item
      (Positions 1-3), 35 in which the probe matched a middle memory set item
      (Positions 6-8), and 35 in which the probe matched a recent memory set item
      (Positions 10-12). Behavioral results revealed recency but not primacy effects in
      both experiments. Recent probes, compared with prime and middle probes, evoked
      ERPs that were more positive from approximately 300 to 400 ms; this enhanced
      positivity occurred in a positive component peaking around 315 ms and a negative
      component peaking around 365 ms. These findings fit more closely with the notion
      of short-term memory as an activation of elements in long-term memory than as a
      distinct memory store (or stores) separate from long-term memory.

PMID- 9564750
TI  - Wrist actigraph measures of physical activity level and ambulatory blood pressure
      in healthy elderly persons.
AB  - A sensitive electronic monitor (Mini-Motionlogger, Ambulatory Monitoring Inc.)
      attached to the wrist was used to record movements during two 24-hr days of
      ambulatory blood pressure (BP) and heart rate (HR) recording in 65 women and 54
      men between the ages of 55 and 79 years, all of whom were in good health. The
      objective was to examine the relationship between various measures of physical
      activity and ambulatory BP and HR during waking and sleeping periods and during
      various diary-defined behaviors. For waking and sleeping periods, neither the
      mean nor the variability of the activity measure was associated with the mean or
      variability of the ambulatory BP and HR measures in between-subjects
      correlational analyses. Within-subject analyses showed little evidence of
      significant covariation between activity and BP or HR during either waking or
      sleeping conditions with most participants showing a slightly positive
      association. The activity measure discriminated between behaviors associated with
      little effort (watching television) versus more energetic behaviors (walking).
      Activity accounted for a relatively small amount of the difference in BP or HR
      related to overall state (wake, sleep), posture (stand, sit), and social
      condition (being with family vs. being with friends). The utility of electronic
      activity monitoring for studies of BP and HR in natural settings is discussed.

PMID- 9564751
TI  - ERP effects of intermodal attention and cross-modal links in spatial attention.
AB  - Effects of intermodal attention AND of cross-modal links in spatial attention on
      visual and auditory event-related potentials (ERPs) were investigated in two
      experiments where participants had to attend to one stimulus modality (audition
      or vision) to respond to infrequently presented targets whenever these were
      presented at a relevant location (indicated by a cue). The ERP effects of
      intermodal attention (measured by comparing the ERPs elicited by visual and
      auditory stimuli when the respective modality was relevant or irrelevant) were
      differently distributed in vision and audition, suggesting that intermodal
      attention operates by a selective modulation of modality-specific areas. Similar
      ERP effects of spatial attention (measured by comparing the ERPs to stimuli at
      cued and uncued locations) were elicited at midline electrodes in vision and
      audition. With one notable exception, these effects were also present when
      attention was directed within the other modality, suggesting the existence of
      cross-modal links between vision and audition in the control of transient spatial
      attention.

PMID- 9564752
TI  - Effect of self-focused attention on the startle reflex, heart rate, and memory
      performance among socially anxious and nonanxious individuals.
AB  - The present study examined the effect of self-focused attention on the startle
      reflex and heart rate and assessed the assumption that socially anxious
      individuals become self-focused in evaluative situations. Twenty-five high and 30
      low socially anxious men performed a digit recall task under evaluative or
      nonevaluative instructions. Half of the trials were performed under self-focused
      conditions and half under non-self-focused conditions. Self-focus led to larger
      startle responses among socially anxious individuals and had no effect on heart
      rate. Self-focus combined with evaluation led to poorer recall performance among
      all subjects. Results provide evidence against a directional change in attention
      during self-focused attention and favor the view that self-focus increases access
      to self-relevant thought content and decreases available processing resources.

PMID- 9564753
TI  - The ensemble-averaged impedance cardiogram: an evaluation of scoring methods and
      interrater reliability.
AB  - The interrater reliability and concurrent validity of two methods of scoring the
      ensemble-averaged impedance cardiogram were evaluated. Impedance cardiographic
      and electrocardiographic signals were recorded from 40 undergraduate men and
      women during a baseline rest period and a vocal mental arithmetic task period.
      Recordings were scored by four rates using a conventional method, involving
      ensemble averaging after careful editing of beat-to-beat waveforms, and a
      streamlined method, involving ensemble averaging without beat-to-beat editing.
      Intraclass correlations for interrater reliability exceeded .92, whereas
      intraclass correlations for concurrent validity exceeded .97, indicating
      excellent agreement between rates and scoring methods for all cardiac measures.
      The streamlined method was significantly faster than the conventional method. The
      results indicate that variations in beat-to-beat editing do not constitute a
      serious source of error in the ensemble-averaged impedance cardiogram and support
      the interrater reliability and concurrent validity of the two scoring methods.

PMID- 9564754
TI  - Assessing parental history of hypertension: father (and mother) knows best!
AB  - In hypertensive risk studies, offspring reports are often used to establish
      parental history of hypertension. This method is simple and less costly than
      contacting parents and has been reported to be > or = 84% accurate when compared
      with parental confirmation. The present study examined two components that
      contribute to overall accuracy: sensitivity (correct identification of high blood
      pressure) and specificity (correct identification of normal blood pressure).
      Undergraduate volunteers (282 women, 211 men) provided parental blood pressure
      information, and then blood pressure history questionnaires were mailed to their
      biological parents. Comparison of offspring and parent reports revealed a
      combination of high specificity (92.9%) and low sensitivity (68.2%), suggesting
      that offspring reports may be misleading when attempting to identify hypertensive
      parents.

PMID- 9564755
TI  - Probing affective pictures: attended startle and tone probes.
AB  - Reflexive eyeblinks to a startle probe vary with the pleasantness of affective
      pictures, whereas the corresponding P300 varies with emotional arousal. The
      impact of attention to the probe on these effects was examined by varying task
      and probe type. Probes were either nonstartling tones or startling noises
      presented during affective picture viewing. Half the participants performed a
      task requiring attention to the probes; the other participants were told to
      ignore the probes. Blinks to the startle probe varied with picture pleasantness
      for both task and nontask conditions. In contrast, P300 magnitudes for both
      startle and tone probes were reduced during emotionally arousing pictures,
      irrespective of pleasantness, in task and nontask conditions. Further, attending
      to the startle probe prompted an augmentation of N100 during unpleasant pictures.
      The data suggest that affective modulation of probe responses reflects obligatory
      processes in picture perception.

PMID- 9564756
TI  - Memory-driven processing in human medial occipital cortex: an event-related
      optical signal (EROS) study.
AB  - Memory-driven processing in medial occipital areas (Area V1 and immediately
      adjacent structures) was investigated noninvasively using the event-related
      optical signal (EROS). Subjects viewed two letter stimuli presented in the left
      and right hemifields, respectively. They then viewed a centrally presented test
      letter and had to indicate whether this letter was the same as either of the
      letters presented earlier. The initial EROS response to the test stimulus in
      medial occipital areas (latency: 50-150 ms) was unilaterally suppressed in the
      hemisphere previously exposed to the same stimulus. This finding suggests that
      medial occipital cortex activity is modulated by a rapidly adapting hemispheric
      specific pattern recognition mechanism.

PMID- 9564758
TI  - Health, disease and society in view of WHO health policy.

PMID- 9564757
TI  - [The course of the past twenty years of mass-screening for congenital metabolic
      disorders: racial difference in PKU genotypes].

PMID- 9564759
TI  - Neonatal screening: current trends and quality control in the United Kingdom.
AB  - Neonatal screening for phenylketonuria (PKU) and congenital hypothyroidism (CHT)
      is universal across the UK using heel prick blood collected at 6-14 days of age.
      Additional programmes for sickle cell disorders, cystic fibrosis, Duchenne
      muscular dystrophy and galactosaemia are provided in some areas. The number of
      inherited metabolic disorders (IMDs) has greatly increased since the introduction
      of PKU screening, and there have been major advances in treatment, e.g. organ
      transplantation, drug therapy. Recent developments in technology have expanded
      the possibilities for screening using the heel prick blood specimen, particularly
      the application of tandem mass spectrometry. There is a case for introducing
      tandem mass spectrometry, limited to clearly defined diseases where specificity
      is adequate and there are satisfactory diagnostic tests. Any change in newborn
      screening to a much broader group of disorders must be carefully introduced and
      monitored preferably as a pilot study. A key component of a laboratory screening
      service is quality control. There are well established UK programmes for PKU and
      CHT. Consideration of the needs for other disorders is now an important priority.

PMID- 9564760
TI  - [Quality control in aspiration biopsy cytology].
AB  - Comparison and quality control of our experience of thyroid cytology (784
      samples) and breast cytology (1,202 samples) were reported. False positive rate
      and other parameters were superior in breast cytology than thyroid. It may be due
      to the fact that cytological diagnostic criteria for follicular thyroid carcinoma
      from follicular adenoma is not established yet. More suspicious diagnosis in
      thyroid than breast also give low incidence of malignancy in thyroid suspicious
      diagnosis. As recommended by a guideline for both thyroid and breast cytology
      from the Papanicolaou society et al, conservative handling and protective
      diagnosis may help to reduce false positive and false negative rates.

PMID- 9564761
TI  - [Cytologic evaluation of dry eye by brushing procedure: value of slide
      preparation by ThinPrep technique].
AB  - Recent clinical trials have indicated that an automated smear apparatus (ThinPrep
      process) of sample preparation has great diagnostic sensitivity. In this study,
      conjunctival brush cytology prepared using the ThinPrep method was applied in
      ocular surface disorders especially for dry eye status. To assess its diagnostic
      value in cellular samples, 35 patients with keratoconjunctivitis sicca (KCS) and
      12 normal volunteer patients were examined using this technique. Conjunctival
      cells from normal controls revealed fine chromatin and polyhedral cytoplasm
      without keratinized cytoplasm. However, cellular samples from KCS revealed
      increased keratinized cells with pyknotic nuclei. They also contained extremely
      elongated cells. In KCS patients, the mean numbers of keratinized cells were
      significantly higher (32.3 cells/300 cells) than those of the normal control
      group (0.2 cells/300 cells). In patients with KCS, inflammatory cell counts were
      also higher than those of normal controls. Conjunctival cytology by the ThinPrep
      method obviously deserves additional trials as an adjunct to cytological
      evaluation of dry eye status, especially for quantitative ocular evaluation of
      various ocular lesions.

PMID- 9564762
TI  - [Cytopathology and histopathology of human papilloma virus].
AB  - Human papilloma viruses (HPV) have been regarded seriously not only as an
      important agent causing sexually transmitted disease, but also because of its
      association with malignant transformation. Over 70 types of HPV are known, of
      which 30 types have been detected in specimens from the cervix. These have been
      classified into a low risk group, a high risk group and an intermediate group
      according to their association with malignant transformation. Therefore,
      diagnosis of cervical HPV infection and to a certain extent the HPV type are
      extremely important. Diagnostic methods of HPV infection include morphological
      methods such as cytological, pathological and electron microscopical diagnoses;
      DNA hybridization methods such as Southern blot hybridization (SBH) and Dot blot
      hybridization (DBH); and a combination of the two methods such as in situ
      hybridization (ISH), in situ polymerase chain reaction (in situ PCR) and
      polymerase chain reaction-in situ hybridization (PCR-ISH). Morphological methods
      using koilocytosis as an indicator have a low detection rate for HPV. Although
      ISH, in situ PCR and PCR-ISH have lower sensitivity that SBH and DBH, they enable
      visual localization of the detected DNA in cells or tissues. These methods are
      therefore important for cytopathologists and histopathologists. In this study, we
      report the morphological characteristics of HPV, as well as the advantages,
      disadvantages and detection rates of the various diagnostic methods.

PMID- 9564763
TI  - [Clinical diagnosis of thrombosis and blood coagulation tests].
AB  - Blood coagulation tests are useful to diagnose some thrombotic diseases.
      Particularly, these tests are valuable for the diagnosis of familiar
      thrombophilia, antiphospholipid antibody syndrome (APS) and disseminated
      intravascular coagulation (DIC). For the diagnosis of thrombophilia,
      determinations of both biological activity and antigen level of antithrombin III,
      protein C and protein S are important for initial screening. Since activated
      protein C (APC) resistance is extremely rare in Japanese, APC resistant test that
      based on APTT, is unnecessary to include as one of the screening tests. Detection
      of activity and antigen level of either plasminogen or fibrinogen is recommended
      to screen the plasminogen deficiency or dysfibrinogenemia. Determination of lupus
      anticoagulant is needed for the diagnosis of APS. At this time, the dilute
      phospholipid APTT (dAPTT) or the dilute Russell viper venom time (dRVVT) may be
      useful as a screening test for LA because procedure of these tests are basically
      simple to perform in Japanese laboratory. In the next step, cross mixing test of
      dAPTT (or APTT) should be perform to make a diagnose of LA more solid. Final
      confirm tests can be conveniently carried out with kit of either STACLOT or LA
      CONFIRM. Platelet count and FDP (or FDP D dimer) assay are two essential tests
      for the diagnosis of DIC. Criteria of diagnosis for DIC recommended by Blood
      Coagulation Research Group of Japanese Ministry of Health and Welfare is not
      unnecessarily appropriate for practical use. TAT and PIC can be a good laboratory
      tests for early detection of hypercoagulable state in patients with DIC.

PMID- 9564764
TI  - [Molecular genetics of cardiovascular diseases].
AB  - This review introduces recent progress in molecular genetics of cardiovascular
      diseases. Many genes and their mutations causing familial cardiovascular diseases
      have been discovered, including familial hypertrophic cardiomyopathy which is
      caused by mutated cardiac beta myosin heavy chain, light chains, troponin T,
      troponin I, or alpha-tropomyosin, and long QT syndrome by KvLQT1, HERG, minK or
      cardiac voltage-dependent Na channel mutation. The mutations in causative genes
      can affect clinical courses of diseases; amino acid substitutions of cardiac beta
      myosin heavy chain with charge changes seem to cause poorer prognosis of
      hypertrophic cardiomyopathy. Besides monogenic diseases, there are many
      cardiovascular diseases affected with genetic polymorphisms, such as
      hypertension, ischemic heart disease and atherosclerosis. Specific amino acid
      mutations or polymorphisms in the promoter region of the genes are known to
      become a risk factor of these diseases. Polymorphisms of genes encoding
      apolipoprotein E, angiotensin converting enzyme, angiotensinogen and endothelial
      NO synthase (ecNOS) have been well characterized as an important risk factor of
      cardiovascular diseases. We recently found a novel gene which seems to affect
      human aging phenotype and vascular endothelial function. It is important as a
      future study to clarify the regulatory mechanisms of the klotho gene in the
      cardiovascular system and the clinical significance of klotho gene polymorphisms.

PMID- 9564765
TI  - [Beta(+)-thalassemia (-31CapA-->G) homozygosity discovered on the mass medical
      examination: diagnosis for beta-thalassemia and DNA analysis].
AB  - A 44-year-old Japanese male showed a high value of HbF (14.3%) in an assay of
      glycated Hb (HbA1c) by use of HLC-723GHb II system. The proband was asymptomatic
      although he was found to be anemic ten years ago. The hematological examination
      revealed microcytosis, hypochromia and slight reticulocytosis (3.7%). Serum iron
      level was high (245 g/dl). Blood smear revealed aniso-poikilocytosis with
      scattered target cells. Hb analysis showed a remarkable increase of HbA2 (8.6%)
      as well as the high HbF cited above, but no abnormal Hb was detected. The
      beta/alpha ratio of globin biosynthesis in reticulocytes was decreased to 0.25.
      DNA sequencing of the beta-globin gene disclosed that the proband was homozygous
      for beta (+)-thalassemia mutation-31CapA-->G. This mutation was linked to A gamma
      T gene and haplotype -(-)+2(-)+2-. His parents and two daughters were
      heterozygous for the mutation. They were anemic and had increased HbA2 levels of
      4.36-5.43%. The beta/alpha ratios of globin biosynthesis were 0.61-0.81.

PMID- 9564766
TI  - [Measurement of levels of plasma endothelin-1 and serum nitrate anion in patients
      with sepsis].
AB  - Recently much attention has been paid to the circulatory disturbance and
      peripheral vascular damage in patients with sepsis and septic shock. We intended
      to elucidate the interaction between nitric oxide (NO) and endothelin (ET)-1
      under various pathological conditions by measuring the concentrations of NO3-,
      the principal metabolite of NO and immunoreactive ET-1. In cases with good
      prognosis after the septic shock, ET-1 was significantly higher as compared with
      these in sepsis without shock. In lethal cases with septic shock, these
      parameters were abnormally high as compared with the survived case. These levels
      elevated as the degree of severity progressed. When patients recovered from the
      septic shock, plasma ET-1 levels rapidly decreased. These results may mean that
      the level of the concentration of ET-1 plays a key role for prevention of the
      multiple organ failure even after the recovery from septic shock. The elevated
      level of NO3- during the initial several days in septic shock will mean that NO
      is acting to prevent platelet aggregation and to keep blood flow by dilating the
      arteries during septic shock. On the contrary, it may also be suggested that the
      elevated level of NO3- and ET-1 leads to the dysfunction of vascular endothelial
      cells and the apoptosis.

PMID- 9564767
TI  - [The measurement of antioxidant activity in human plasma using cumene
      hydroperoxide].
AB  - We describe a new method using cumene hydroperoxide to determine antioxidant
      activity (AO) in human plasma. We used a kit (Determiner LPO: Kyowa Medex Co.,
      LTD. Tokyo Japan) for the determination of lipid peroxides in plasma or serum. 30
      microliters 1 of sample was mixed with 70 microliters 1 of cumene hydroperoxide
      (50 nmol/ml) and incubated at 30 degrees C for 120 min before analysis. Samples
      were mixed with 1.0 ml of reagent-I (Determiner LPO) and incubated at 30 degrees
      C for 5 min. Then 2.0 ml of reagent-II (Determiner LPO) was added and incubated
      at 30 degrees C for 10 min, at which time the absorbance at 675 nm was measured.
      AO were calculated using the following formula: AO nmol/ml = 35 nmol/ml-(Es
      Eb)/(Estd-Eb) x 35 nmol/ml (Es = sample abs., Eb = blank abs., Estd = standard
      abs.). Within-run precision for plasma AO was 2.3%. AO in plasma samples stored
      for 4 h at 4 degrees C was decreased by 1 nmol/ml. After 3 h at room temperature,
      AO was decreased by the same amount. Because this method measured ascorbic acid,
      alpha-tocopherol, glutathione peroxidase and quercetin as antioxidant compounds,
      we were able to measure antioxidant activity in human plasma. Our reference
      values were calculated from the volunteers group which consisted of 172 students
      and 82 soldiers. The reference intervals for plasma AO by this procedure were
      15.4-20.9 nmol/ml.

PMID- 9564768
TI  - [The significance of determination of urinary type IV collagen concentrations
      from a random urine collection in patients with non-insulin dependent diabetes
      mellitus].
AB  - Recently, we have developed a highly sensitive assay system for quantitative
      measurement of urinary type IV collagen. To obtain a basic evaluation of the
      assay system we used urine specimens, collected randomly and studied the relation
      to diabetic nephropathy in patients with non-insulin dependent diabetes mellitus
      (NIDDM). It was shown that this assay system could measure the samples without
      concentrating the urine. Urinary sediments which were reported to interfere with
      the assay could be removed by adding Tris-buffer. In the clinical studies,
      urinary type IV collagen concentrations were significantly higher in patients
      with NIDDM regardless of the presence or the absence of albumin. Cases with
      abnormal values of urinary type IV collagen in the normal albuminuria group were
      41.6%, while those with abnormal values of urinary transferrin excretion were
      31.0%. Furthermore, among the normal albuminuria group, glycosylated hemoglobin
      (HbA1c) levels were higher in the groups of abnormal values of urinary type IV
      collagen than those within the reference values. These results obtained herein
      suggest that urinary type IV collagen could be a useful marker for the early
      stage of diabetic nephropathy.

PMID- 9564769
TI  - [Number of apolipoprotein(a) kringle IV repeats and mobility of isoforms in
      PAGE].
AB  - Serum apo(a) isoform sizes were determined by SDS-polyacryl amide gel
      electrophoretic (PAGE) method, followed by a high sensitive immunoblotting. The
      relation between the number of apo(a) kringle IV encoding sequences in the apo(a)
      gene, as assessed by pulsed field gel electrophoresis and genomic blotting
      (genotype), and the apo(a) isoforms (phenotype) in SDS-PAGE was evaluated in 78
      individuals. The correlation of apo(a) allele number between phenotype and
      genotype method was high (r = 0.513) in 178 expressed apo(a) alleles. This
      nomenclature is achieved by using standard serum of kringle IV repeats. We
      conclude that this method is an approach to genotyping to designate the
      phenotypes by kringle IV repeats.

PMID- 9564771
TI  - [Assessment of the American College of Rheumatology criteria for the
      classification and reporting of osteoarthritis of the knee].
AB  - Radiological examination is essential in diagnosing osteoarthritis (OA) of the
      knee. However, diagnoses that are not based on radiological examination are
      preferred in epidemiological studies, and the American College of Rheumatology
      (ACR) has recommended classification criteria for OA of the knee based on
      clinical examination, and indicated that these classification criteria were
      appropriate for epidemiological studies. To evaluate the validity of this
      criteria, we examined the interobserver reproducibility as well as the
      sensitivity and specificity of the criteria for outpatient attenders complaining
      knee pain with wide spectrum of rheumatic diseases. As a result, interobserver
      reproducibility was considered good, but both sensitivity and specificity were
      slightly lower than the report by ACR in which representative rheumatic diseases
      such as rheumatoid arthritis were chosen as control. We therefore consider that
      ACR classification criteria for OA of the knee in of value, but that radiological
      examination should be preferred in case it is possible.

PMID- 9564770
TI  - [Detection of apolipoproteins E5 and E7 by a widely used commercial ApoE IFE kit-
      evidence provided by genotyping].
AB  - The purpose of this study is to examine a possibility to detect apolipoprotein
      (apo) E5 and E7 isoproteins with a commercial kit widely used (Phenotyping Apo E
      IFE System, Jokoh Co. LTD., Tokyo) and to clarify the frequency of the rare
      alleles in Central Japan. A total of 1,445 subjects living in Central Japan
      (1,030 hemodialysis patients and 415 apparently healthy individuals) was
      phenotyped for apo E isoproteins with the kit using isoelectric focusing with
      immunoblotting. In 23 subjects, unique apo E4 isoproteins, which migrate more
      basically than apo E4 isoprotein, were found. These unique isoproteins were
      proved to be apo E5 or E7 isoproteins by PCR with restriction fragment length
      polymorphism and with amplification refractory mutation systems, respectively. No
      significant differences in the frequencies of apo E5 or apo E7 alleles were
      observed between healthy individuals and hemodialysis patients (0.011 vs. 0.018,
      NS). The frequencies of apo E5 and E7 alleles were 0.001 and 0.005, respectively,
      in healthy individuals, and 0.003 and 0.005, respectively, in hemodialysis
      patients. These data in Central Japan were consistent with those in Western Japan
      (Matsunaga, et al, Clin Genet, 1995). These results indicate that the commercial
      kit is applicable to detect the rare alleles, apo E5 and E7 alleles and that the
      frequencies of the rare alleles in Central Japan are similar to those in Western
      Japan.

PMID- 9564772
TI  - [Clinical relapse of rheumatoid arthritis (escape phenomenon) during low-dose
      methotrexate therapy].
AB  - OBJECTIVE: To clarify the incidence and background of clinical relapse (escape
      phenomenon) during low-dose methotrexate therapy for rheumatoid arthritis.
      METHODS: Seventy one patients with rheumatoid arthritis (RA) were analyzed. They
      were started on therapy with methotrexate (MTX) between April 1, 1991 and May 30,
      1995. Among them, 60 patients showed clinical improvement within 6 months after
      the start of the therapy and were subjected to the analysis for clinical relapse
      (escape phenomenon). RESULTS: Twelve patients showed an initial improvement
      followed by a relapse with increased serum CRP and number of painful joints
      despite the MTX therapy was continued. Two types of the relapses were seen; (1)
      early, escape (relapse after an initial brief improvement) in 7 patients, and (2)
      late escape (relapse after a long-term improvement with MTX therapy) in 5
      patients. The early escape was seen at 9.0 +/- 0.7 months after the start of
      therapy while the late escape was seen at 23.3 +/- 4.8 months. Patients with both
      types of escape phenomenon had the longer duration of the disease and more
      advanced stage. There was no relationship between clinical relapse and age,
      baseline RA activity, MTX dose, or concurrent use of corticosteroids and other
      disease modifying anti-rheumatic drugs. The efficacy of MTX for RA was restored
      by increasing dose of MTX in 11 patients. CONCLUSION: These results suggest that
      clinical relapse is not rare in RA patients during low-dose methotrexate therapy,
      but could be improved by increasing dose.

PMID- 9564774
TI  - [A patient with acute sarcoidosis associated with fever, polyarthritis, and
      erythema nodosum: a typical of Lofgren's syndrome].
AB  - A 26-year-old female was admitted to Aoyama Hospital in February 1996, for
      evaluation of abnormal chest shadows and polyarthritis. She visited our clinic in
      December 1995 with complaints of fever, fatigue, and polyarthralgia which lasted
      for 3 weeks. Two weeks later she developed erythema nodosum on her lower legs
      with the exacerbation of polyarthritis. Erythrocyte sedimentation rate was 108
      mm/hr and CRP 4.9 mg/dl. A chest radiograph showed hilar lymphadenopathy and
      multiple nodular shadows in both lung fields. On admission, she had arthritis of
      the shoulders and knees, erythema nodosum on her lower extremities, and keloid
      like skin lesion on her left knee. Thoracoscopic lung biopsy of nodular lesion
      and skin biopsy of keloid-like lesion revealed noncaseating granuloma of
      epithelioid cells with lymphocytes, macrophages, and giant cells, confirming the
      diagnosis of sarcoidosis. She was cured in three months, and was well and free of
      the symptoms thereafter. Lofgren's syndrome is acute sarcoidosis, characterized
      by arthritis, erythema nodosum, and bilateral hilar lymphadenopathy. This
      syndrome is common in Europe and is closely related to HLA-B8 and DR-3. The
      frequency of HLA-B8 and DR-3 in Japanese is almost 0%, explaining the rare onset
      of this syndrome in Japan. Our case is the second report of typical Lofgren's
      syndrome in Japan, although the patient did not have these HLA loci.

PMID- 9564773
TI  - [The efficacy of combination therapy with prednisolone (PSL) and methotrexate
      (MTX) on radiographic progression in patients with rheumatoid arthritis (RA)].
AB  - A case-controlled study was performed, based on early active RA patients treated
      with MTX; Prednisolone (PSL) was also given in sixteen patients (PSL + MTX group)
      and each of them was matched for age and sex with a control who have never
      received PSL (MTX group). No significant differences in radiographic progression
      were found between the 2 groups. Analysis of radiographic parameters showed that
      CRP, erythrocyte sedimentation rate, and titers of serum rheumatoid factors after
      6 months treatment and their integral amounts during cource were significantly
      high in the patients with marked radiographic progression. There was no
      relationship between radiographic progression and treatment with PSL. These
      results suggested that the indication of PSL therapy for RA is limited for
      patients with the poor decrease in the level of CRP, erythrocyte sedimentation
      rate, and rheumatoid factor by MTX treatment.

PMID- 9564775
TI  - [A case of juvenile rheumatoid arthritis with MPO-ANCA associated nephritis].
AB  - A 12-year-old girl with a main complaint of sever pain on the both knees was
      admitted to our hospital in October, 1995. She gave a three year history of
      recurrent arthralgia and purpuric rashes, and persistent microhematuria and
      proteinuria. She developed vesicles and purpuric rashes on the hands and
      auricles, morning stiffness, fever, uveitis and pericarditis. Laboratory findings
      showed an elevated level of erythrocyte sedimentation rate and iron-deficiency
      anemia. Serum perinuclear pattern ANCA with antimyeloperioxidase specificity (MPO
      ANCA) was positive. A renal biopsy specimen disclosed a focal and segmental
      necrotizing glomerulonephritis with crescents. Our case fulfills the both
      diagnostic criteria for polyarteritis nodosa and juvenile rheumatoid arthritis.
      This is a rare case of MPO-ANCA associated vasculitis in children.

PMID- 9564776
TI  - [Interstitial cystitis in case of primary Sjogren's syndrome].
AB  - A 53-year-old woman who had xerostomia for ten years was admitted to our hospital
      because of refractory lower abdominal pain and pollakisuria of five years
      duration. Although she had undergone surgical treatments including
      cholecystectomy, ovarian cystectomy and groin hemiorrhaphy, she still suffered
      from abdominal symptoms. A diagnosis of interstitial cystitis was confirmed by
      hydraulic distention during a cystoscopic examination and by histopathological
      examination of the bladder. Her symptoms disappeared soon after the cystoscopic
      procedure, which also had a therapeutic effect of interstitial cystitis.
      Laboratory findings revealed hypergammaglobulinemia, a high titer of rheumatoid
      factor, positive anti-nuclear antibody, and positive anti-SS-A/Ro antibody. She
      was diagnosed as having primary Sjogren's syndrome based on the results of a gum
      test (8.5 ml/ 10 min), sialography (Stage II), and a positive minor salivary
      gland biopsy. Starting one month after the hydraulic distention, her abdominal
      symptoms gradually reappeared along with elevation of her serum IgG level. These
      features were markedly improved with 30 mg/day of oral prednisolone, which was
      then successfully tapered. These results suggested that interstitial cystitis in
      this case was caused by immunological abnormalities associated with Sjogren's
      syndrome.

PMID- 9564777
TI  - [A recovered case of SLE with central nervous system involvement who relapsed
      presenting new symptoms associated with development of serum anti-Sm antibody].
AB  - A rare SLE patient with central nervous system involvement (CNS-SLE) who relapsed
      presenting new symptoms associated with the development of serum anti-Sm antibody
      and was then successfully treated with cyclophosphamide (CY) pulse therapy is
      presented here. A 47-years old housewife was admitted to Kushiro City General
      Hospital because of fever, limb erythema and drowsy consciousness in September
      1995. On the basis of convulsion, proteinuria, leukopenia, thrombopenia, serum
      positive tests for both anti-nuclear antibody and anti-SSA antibody and low
      complement levels, as well as elevations of IgG index and IL-6 in the
      cerebrospinal fluid (CSF), she was diagnosed as having CNS-SLE. Serum tests for
      anti CL-beta 2 GPI antibody and lupus anticoaglant was negative. Serum test for
      HBs antigen was positive. She was treated successfully with methylprednisolone
      (mPSL) pulse therapy and plasma exchange (PE). Prednisolone was gradually tapered
      to the dosage of 17.5 mg per day and she was discharged in April 1996. She was re
      admitted because of fever, an exacerbation of skin eruption and arthralgia in
      October 1996. Serum anti-Sm antibody was found to be positive. mPSL pulse therapy
      was not effective. On the basis of hallucination and elevations of IgG index and
      IL-6 in the CSF, a diagnosis of relapsed CNS-SLE was made. However the level of
      IFN-alpha in the CSF was normal. Although PE was not effective, CY pulse therapy
      was markedly effective.

PMID- 9564778
TI  - [Surgical synovectomy in rheumatoid arthritis].

PMID- 9564779
TI  - [Characterization of crystals induced arthritis and periarthritis].

PMID- 9564780
TI  - [Ca2+/calmodulin-dependent protein kinase cascade and its physiological
      function].

PMID- 9564781
TI  - [Molecular mechanism of defense system against photooxidative damage in
      photosynthetic organisms--possibility of creation of plants with tolerance to
      photooxidative damage].

PMID- 9564782
TI  - [Structure and function of hormone-like peptides in plants].

PMID- 9564783
TI  - [Turning point toward new ageing science].

PMID- 9564784
TI  - [Molecular mechanism of invadopodia formation].

PMID- 9564785
TI  - [Development of anti-HIV drugs targeted to the coreceptors].

PMID- 9564786
TI  - [Molecular mechanisms of the emergence of enterohemorrhagic Escherichia coli
      O157:H7 and newly emerged Vibrio cholerae].

PMID- 9564787
TI  - [Recent progresses in mechanisms of eukaryotic DNA replication].

PMID- 9564788
TI  - [Review of pH measurement (3): Practice of pH meter based on glass electrode
      method (2)].

PMID- 9564789
TI  - Natural organic compounds that affect to microtubule functions.
AB  - Microtubules (MT), composed of a protein tubulin (TN) alpha,beta-heterodimer with
      concomitant other proteins, microtubule associated proteins (MAPs and tau), are
      known to be the main component of spindles in a mitotic apparatus of eucaryotic
      cells, and are also involved in many other basic and essential cell functions.
      There are a number of natural and synthetic compounds that interfere with MT
      function to cause the mitotic arrest of eucaryotic cells. Such antimitotic agents
      show a broad biological activity, and can be used for medicinal and agrochemical
      purposes. On the other hand, they are also important as the biochemical tools for
      understanding the dynamics of MT network. Most of such antimitotic agents, with a
      few exceptions, bind to beta-TN. Among them, colchicine (CLC), vinblastine (VLB)
      and taxol have been of major importance in biochemical studies of MT and in
      studies of their intracellular functions. The former two both inhibit MT assembly
      but their binding sites on beta-TN are different; CLC-site and VLB-site, and many
      MT inhibitors bind to either sites. Taxol bind to TN at a site other than CLC
      site and VLB-site, and promote MT assembly. We have worked on a variety of
      antimitotic agents that bind to CLC, VLB or taxol-site, in discoveries,
      structures, biological actions and/or interactions with TN. In this paper, I
      summarized the results of our studies on VLB-site ligands; (1) rhizoxin (RZX),
      isolated as a phytotoxin produced by a plant pathogenic fungus, and its related
      compounds, (2) derivatives of ansamitocin P-3 (ASMP3) (maytansinoid: MAY),
      isolated as a cytotoxic metabolite of an Actinomycete, (3) phomopsin A (PMSA),
      isolated as a mycotoxin produced by a plant parasitic fungus, (4) dolastatin 10
      (DLS10), isolated as a cytotoxic metabolite of a see animal, (5) ustiloxins (USL)
      A-F, isolated as a mycotoxin produced by a plant pathogenic fungus, (6)
      arenastation A (ARSA), isolated as a cytotoxic metabolite of a sponge, and its
      synthetic analogs. From our studies on interactions of these VLB-site ligands
      with TN, we showed that the presence of a distinct RZX/MAY-binding site which
      only partially overlap with VLB-site, and that PMSA, DLS10, USLs and ARSA bind to
      the RZX/MAY site. RZX, ASMP3 and ARSA inhibit the growth of a variety of fungi,
      including Aspergillus nidulans. In order to obtain information as to the drug-TN
      interaction at the RZX/MAY site, RZX-resistant beta-TN gene mutants were isolated
      from RZX-sensitive wild-type A. nidulans. In all the beta-TN gene mutants, single
      amino acid (100th) alteration, asparagine-to-isoleucine, was observed. Sequence
      displacement experiments confirmed that this alteration conferred resistance to
      RZX and ASMP3, and also to ARSA. This resistance mechanism was further verified
      with yeasts Schizosaccharomyces pombe and Saccharomyces serevisiae. All the
      natural ligands mentioned above show potent cytotoxicity against human and murine
      tumor cells, but VLB, PMSA, DLS10 and USLA are inactive to both RZX-sensitive and
      -resistant fungal strains.

PMID- 9564790
TI  - [Adhesive properties and related phenomena for powdered pharmaceuticals].
AB  - This report deals with adhesive properties and related phenomena of powdered
      materials including pharmaceuticals. The adhesive force between a powder particle
      and substrate as well as the tensile strength of a powder bed and tablet was
      measured. Various factors were found to affect powder adhesion. Physical
      properties such as the size, shape and surface roughness were examined. The
      adhesive force between a particle and substrate decreased remarkably in the
      presence of ultrafine particles, which is of interest since the addition of
      adequate amount of "glidant" causes an increase in powder fluidity. From a
      pharmaceutical point of view, temperature and humidity were essential to particle
      adhesion. For several organic substances, the adhesive force increased
      significantly at homologous temperatures more than ca. 0.7, suggesting the
      sintering mechanism to be operative. The adhsive force between polymer films and
      glass beads varied according to polymer and relative humidity. A close
      correlation of water sorbed by the polymer film with adhesive force was noted. In
      connection with powder fluidity, compaction properties were studied by the
      centrifugal and tapping methods. Apparent adhesion defined as the ratio of the
      adhesive force between two contacting particles to the external force acting on a
      particle was noted to be the primary determinant of the void fraction or the
      porosity of the powder bed, indicating that the probability of particle
      displacement essentially depended on apparent adhesion.

PMID- 9564791
TI  - [Pharmacokinetics of (-)-, (+)- and (+/-)-norephedrine. Plasma concentrations,
      serum protein binding and urinary excretions].
AB  - The pharmacokinetics of norephedrine enantiomers were determined after the
      independent i.v. administration of (+/-)-norephedrine (20 mg/kg), (-)
      norephedrine (10 mg/kg), and (+)-norephedrine (10 mg/kg) to rats. Significant
      differences were observed in the pharmacokinetic parameters of each enantiomer
      when the enantiomers were administered singly and as a racemate. For example, the
      values of total body clearance (Cltot) and urinary excretion clearance (Clr) of (
      )-norephedrine administered as a racemate were higher than those of the
      norephedrine enantiomer administered singly. The areas under the curve of
      concentration versus time (AUC) of (-)-norephedrine administered as a racemate
      had a tendency to increase. While Cltot of (+)-norephedrine administered as a
      racemate showed a lower value and AUC showed a higher value. The value of Clr of
      (+)-norephedrine administered as a racemate showed a tendency to decrease. There
      was no difference in the in vitro serum protein binding of (-)- and (+)
      norephedrine. The data from this study reveal that pharmacokinetic interactions
      exist between the norephedrine enantiomers and also reveal that the serum protein
      binding is not concerned with those interactions. The differences in the
      pharmacological effects after the individual administration of (-)-norephedrine
      or (+/-)-norephedrine may be coused by the differences in their concentrations in
      the plasma.

PMID- 9564792
TI  - [Biological response modifier activity of Lactococcus lactis 332].
AB  - The biological response modifier (BRM) activity of a preparation of heat killed
      cells of Lactococcus lactis 332 which can produce large amount of lactate in
      culture, was investigated in C3H/He and ICR mice. Intraperitoneal injection of
      Lactococcus lactis 332 caused an accumulation of neutrophils and macrophages in
      the peritoneal cavity of the mice, similarly to BRMs used clinically. As a
      parameter of the activation of macrophages, the effect of the Lactococcus lactis
      332 preparation on the production of tumor necrosis factor (TNF) was examined.
      The Lactococcus lactis 332 preparation was revealed to have both priming and
      triggering activities for the production of TNF. The TNF level in the sera
      reached about 1000 IU/ml in mice 2 h after the triggering injection. This
      preparation also stimulated peritoneal macrophages to produce TNF in vitro.
      Intratumoral injection of the Lactococcus lactis 332 preparation regressed MM46
      tumor cells in C3H/He mice. These results suggest that the Lactococcus lactis 332
      preparation is a biological response modifier (BRM) with various activities on
      phagocytes similarly to a streptococcal antitumor agent, OK432, used clinically.

PMID- 9564793
TI  - A multicenter, placebo-controlled study of twice daily triamcinolone acetonide
      (800 microg per day) for the treatment of patients with mild-to-moderate asthma.
AB  - BACKGROUND: National and international guidelines recommend the use of inhaled
      antiinflammatory medications in patients with all but the mildest forms of
      asthma. Twice daily dosing may increase compliance with therapy. OBJECTIVE: We
      sought to evaluate the safety and efficacy of 400 microg twice daily
      triamcinolone acetonide (TAA) compared with placebo in adult patients with mild
      to-moderate asthma who were poorly controlled by beta2-agonist therapy. METHODS:
      We performed a multicenter, randomized, double-blind, placebo-controlled study,
      including a screening visit, a 7- to 21-day pretreatment baseline phase, and a 6
      week double-blind treatment phase. Efficacy was measured by weekly spirometry and
      daily diary recordings of peak flow rates, asthma symptom scores, and albuterol
      use. Eligible patients used albuterol four or more times per day, had total
      asthma symptom scores of 15 or greater (possible total, 60) over 5 of 7 baseline
      days, and had FEV1 measurements of 60% of predicted value or greater. RESULTS:
      One hundred twenty-one patients were randomized to treatment. TAA was superior to
      placebo for all efficacy measures, with significant improvements in asthma
      symptoms, albuterol use, morning and evening peak flow rates, and forced vital
      capacity evident at Treatment Week 1. Significant improvements in other pulmonary
      function measurements were observed after 2 or more weeks. All efficacy variables
      improved progressively throughout the study. CONCLUSIONS: Twice daily TAA (400
      microg) decreased asthma symptoms and improved lung function in patients with
      mild-to-moderate asthma compared with placebo. Therapeutic benefit was evident
      within 1 week and increased throughout treatment.

PMID- 9564794
TI  - Sibship size, birth order, and atopy in 11,371 Italian young men.
AB  - BACKGROUND: Having a low number of siblings and a low birth order has been
      reported to be a relevant risk factor for development of atopic diseases and skin
      sensitization to common inhalants. Although the inverse association of atopy with
      sibship size has been confirmed repeatedly, the association with birth order has
      provided conflicting results. This possibly is due to the relatively small size
      of the population sample examined. OBJECTIVE: The objective of this study was to
      investigate the relation between sibship size, birth order, and atopy in a very
      large population sample, highly homogeneous for age and sex. METHODS: This was a
      retrospective survey of 11,371 Italian young men, 18 to 24 years old, all
      candidates for enrollment in the Italian Air Force. Demographic data had been
      collected by a standard questionnaire. Specific IgE for locally relevant airborne
      allergens had been tested by a multi-RAST assay (CAP-Phadiatop). RESULTS: The
      prevalence of atopy (defined as a high level of specific IgE against inhalants
      [cut-point >1.2 log RU]) was inversely related to the total number of siblings
      (25% in those with no siblings and 9% in those with five or more siblings), with
      a mean of a 3% decrease in prevalence for each added sibling. This relation
      persisted after adjustment for relevant variables such as father's education and
      rural and southern residence. An independent association between birth order and
      atopy was also observed because the decrease in atopy prevalence with increasing
      numbers of older siblings was significantly steeper than that found with the
      number of younger siblings (chi2 = 179, df = 1, p < 0.0001). CONCLUSIONS: In a
      very large and homogeneous population sample of a Mediterranean country, not only
      sibship size but also birth order was significantly associated with atopy. This
      observation further highlights the role of family structure in the development of
      atopy and supports the hypothesis that cross-infections acquired early in infancy
      or in later childhood might prevent development of atopy later in life.

PMID- 9564795
TI  - Antiresorptive therapy in asthmatic patients receiving high-dose inhaled
      steroids: a prospective study for 18 months.
AB  - BACKGROUND: Inhaled steroid therapy is an effective and well tolerated mode of
      therapy for asthma. Although systemic side-effects of inhaled steroids are much
      less common than those found with systemic steroids, the drugs may be absorbed
      through mucosal surfaces. Inhaled steroids have been reported to disturb normal
      bone metabolism, and they are associated with a decrease in bone mineral density.
      OBJECTIVE: We conducted this study to investigate bone density in asthmatic
      subjects receiving long-term high-dose inhaled steroids and the effects of
      supplementation with oral calcium with or without etidronate. METHODS: We
      evaluated thirty-eight Chinese subjects (24 men and 14 premenopausal women; 28
      patients and 10 healthy control subjects) in this prospective study. Patients
      were randomized into three arms: those receiving no supplement, those receiving
      1000 mg/day calcium supplement, and those receiving 400 mg/day cyclical sodium
      etidronate with 1000 mg/day calcium, respectively. The patients and control
      subjects were matched for age, sex, and dose of inhaled steroids. Bone density at
      lumbar spine and hip region was measured by dual energy x-ray absorptiometry with
      a densitometer at baseline and at 6, 12, and 18 months for the asthmatic groups
      and at baseline and at 12 and 18 months for the control group. Serum calcium,
      phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 25
      hydroxyvitamin D, and urinary hydroxyproline/creatine were measured simultaneous
      to bone density assessments. RESULTS: There were 10 control subjects, 10
      asthmatic subjects receiving no supplement, eight asthmatic subjects receiving
      calcium supplement, and 10 asthmatic subjects receiving calcium and etidronate
      therapy, respectively. The mean (+/- SEM) dosages of beclomethasone or budesonide
      for the three groups of asthmatic subjects were 2.2 +/- 0.3, 2.0 +/- 0.2, and 2.0
      +/- 0.2 mg/day, respectively. Mean dietary calcium intake of the study subjects
      was 766 +/- 39 mg/day. At baseline, bone mineral density of the spine in the
      group receiving no supplement was significantly lower than that found in the
      control group (p < 0.05). At 18 months, patients receiving no supplement had
      significantly greater bone loss at the lumbar spine than patients receiving
      etidronate plus calcium lactate-gluconate (CaLG) or CaLG alone (p < 0.05). The
      increase in bone mineral density versus baseline observed in patients receiving
      CaLG with or without etidronate (p < 0.05) probably did not result from increased
      bone formation because serum osteocalcin levels showed a significant reduction in
      all three groups of patients (p < 0.05). An increase in mean serum calcium (p <
      0.05) was seen in patients receiving CaLG with or without etidronate. CONCLUSION:
      Our results suggest that long-term administration of high-dose inhaled steroid
      (>1.5 mg/day) induces bone loss that is preventable with calcium supplementation
      with or without cyclical etidronate. Long-term studies involving more patients
      should follow to confirm these preliminary findings.

PMID- 9564796
TI  - The Melbourne House Dust Mite Study: long-term efficacy of house dust mite
      reduction strategies.
AB  - BACKGROUND: Asthma severity among mite-sensitized individuals appears to be
      related to the degree of mite allergen exposure. OBJECTIVES: The objective of
      this study was to assess the long-term effectiveness of mite avoidance measures
      in the homes of asthmatic children in Melbourne, Australia. METHODS: The
      concentration of house dust mite allergen (Der p 1) was measured on the child's
      mattress surfaces and bedroom floors in 85 homes on 10 occasions over a 16-month
      period. After the first three visits, all mattresses were covered with a
      semipermeable encasement, and carpeted bedroom floors were randomly allocated to
      regular applications of a placebo or an "anti-mite" shampoo. RESULTS: The
      concentration of Der p 1 recovered was initially high in the carpeted bedrooms (n
      = 66) (41.1, 95% confidence interval, 30.7 to 55.0 microg Der p 1 per gm) and
      mattresses (n = 85) (39.6, 27.2 to 57.7). During the initial observation period
      the concentration of mite allergen fell in the treatment, placebo, and parental
      control groups. During the seven treatment periods, no differences were seen
      between the Der p 1 concentrations in the groups using the "anti-mite" shampoo,
      placebo shampoo, or the parental control group (e.g., at visit 4; 12.6, 8.2 to
      19.5; 14.8, 8.6 to 25.1; and 12.0, 8.1 to 17.7 microg/gm, respectively). In
      contrast, the concentration of Der p 1 in samples from uncarpeted floors and
      mattress encasements was low (4.1, 2.1 to 8.0 microg/gm and 4.2, 2.6 to 6.5
      microg/gm, respectively) and insufficient dust for analysis was frequently
      obtained from these sites. CONCLUSIONS: There was no additional benefit from the
      use of an "anti-mite" shampoo. The absence of carpets and the use of mattress
      encasements was a useful long-term strategy for mite allergen avoidance.

PMID- 9564797
TI  - Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when
      used in the treatment of adult patients with chronic asthma.
AB  - BACKGROUND: Airway inflammation is a hallmark of asthma, therefore current
      treatment recommendations include the use of inhaled glucocorticosteroids (GCS).
      However, there is little evidence that the effects of inhaled GCS are dose
      dependent. OBJECTIVES: The objective of this study was to assess the efficacy and
      safety of a second-generation GCS, budesonide, delivered by Turbuhaler, in adults
      with chronic asthma. METHODS: In a 12-week, randomized, double-blind,
      multicenter, parallel-group study, 473 subjects 18 to 70 years of age received
      either placebo or budesonide (200, 400, 800, or 1600 microg total daily dose)
      administered twice daily. Primary efficacy end points were mean change from
      baseline for FEV1 and morning peak expiratory flow. Safety was assessed by
      reported adverse events and by a cosyntropin-stimulation test. RESULTS: The mean
      baseline FEV1 was 63% to 66% of predicted normal value between groups. All doses
      of budesonide were more effective than placebo (p < 0.001). The mean changes in
      morning peak expiratory flow were 12, 22, 27, and 30 L/min in the 200, 400, 800,
      and 1600 microg budesonide total daily dose groups, respectively, and -27 L/min
      for the placebo group. A statistically significant dose-response effect for the
      mean change from baseline over the 12-week study was seen for both morning peak
      expiratory flow and FEV1. Budesonide-treated subjects also demonstrated
      significant reduction in asthma symptoms and bronchodilator use compared with
      placebo. There were no clinically significant differences in treatment-related
      adverse experiences among groups. CONCLUSIONS: Budesonide administered by
      Turbuhaler exhibited a dose response and was effective at low doses. It was well
      tolerated and significantly more effective than placebo.

PMID- 9564798
TI  - Rapid induction of clinical response with a short-term high-dose starting
      schedule of budesonide nebulizing suspension in young children with recurrent
      wheezing episodes.
AB  - BACKGROUND: There are no data currently available on the correct schedule for the
      initiation of treatment with nebulized suspension of budesonide in children with
      recurrent wheezing episodes. We compared the efficacy and safety of starting with
      a high dose followed by a stepwise decrease to a continuous low dose. METHODS: In
      a double-blind design, 42 children aged 6 months to 3 years were randomly
      allocated to receive either a high starting dose of 1 mg budesonide twice daily
      followed by a stepwise decrease of 25% every second day for 1 week (group A) or a
      low dose of 0.25 mg twice daily for 1 week (group B). Efficacy was assessed with
      daily symptom scores and the systemic effect of the corticosteroids with the
      adrenocorticotropic hormone test. RESULTS: The two groups were comparable for all
      parameters evaluated. During the first week of treatment, there was a significant
      decrease in asthmatic symptomatology only in group A: a 59% decrease for wheezing
      (p = 0.0001), 39% for diurnal cough (p = 0.036), and 39% for nocturnal cough (p =
      0.04). Mean time to clinical response was 3.0 days in group A and 5.7 days in
      group B (p = 0.02). This early improvement was sustained for the rest of the
      follow-up period. The high dose starting schedule was not associated with any
      change in serum cortisol level. CONCLUSIONS: The administration of nebulized
      suspension of budesonide at a high starting dose schedule followed by a rapid (1
      week) stepwise decrease yields a significant early improvement in asthma symptoms
      and causes no change in serum cortisol levels.

PMID- 9564799
TI  - Effects of repeated once daily dosing of three intranasal corticosteroids on
      basal and dynamic measures of hypothalamic-pituitary-adrenal-axis activity.
AB  - BACKGROUND: Intranasal corticosteroids are regarded as the first-line treatment
      for allergic rhinitis, but few studies have directly compared their systemic
      effects. OBJECTIVE: We sought to compare the hypothalamic-pituitary-adrenal (HPA)
      axis suppression with three intranasal corticosteroids in terms of basal and
      dynamic adrenocortical activity. METHODS: Sixteen healthy volunteers (mean age,
      30.7 years) were studied in a single-blind, randomized, four-way crossover study
      comparing placebo with 200 microg/day fluticasone propionate (FP), 220 microg/day
      triamcinolone acetonide (TAA), and 336 microg/day beclomethasone dipropionate
      (BDP). After 4 days of treatment, an overnight urine collection was taken for
      cortisol and creatinine excretion starting at 10 PM (14 hours after the fourth
      dose), and blood was taken for serum cortisol at 8 AM (24 hours after the fourth
      dose) and after stimulation with adrenocorticotrophic hormone (ACTH) (0.5
      microg). RESULTS: For overnight urinary cortisol excretion compared with placebo
      (20.8 nmol), there was a significant (p < 0.05) degree of suppression with FP
      (11.8 nmol) but not with TAA (16.0 nmol) or BDP (16.5 nmol). In terms of fold
      difference (95% CI for difference) from placebo, this amounted to 1.75-fold (1.01
      to 3.03) for FP (43% suppression), 1.30-fold (0.75 to 2.25) for TAA (23%
      suppression), and 1.26-fold (0.73 to 2.18) for BDP (21% suppression). There was
      also a trend towards suppression of overnight urinary cortisol/creatinine
      excretion, but this was not statistically significant (placebo, 5.2 nmol/mmol;
      TAA, 5.0 nmol/mmol; BDP, 4.3 nmol/mmol; and FP, 4.3 nmol/mmol). Values for serum
      cortisol before and after ACTH stimulation showed no significant suppression.
      CONCLUSION: Suppression of overnight urinary cortisol occurred with intranasal FP
      (43%), TAA (23%), and BDP (21%), although this was only statistically significant
      with FP. None of the drugs were associated with blunting of the response to ACTH
      stimulation. Further studies are indicated to establish whether the systemic
      effects of inhaled and intranasal corticosteroids are additive.

PMID- 9564800
TI  - The efficacy of slow versus faster inhalation of cromolyn sodium in protecting
      against allergen challenge in patients with asthma.
AB  - BACKGROUND: Approximately one third of patients with allergy-induced asthma who
      are treated with aerosolized cromolyn sodium (CS) fail to achieve a full
      therapeutic effect. This lack of effectiveness could involve nonhomogeneous
      distribution of drug in the lung as a result of high inspiratory flow rates.
      OBJECTIVE: We sought to determine the efficacy of slow versus faster inhalation
      of CS in protecting against allergen challenge in patients with asthma. METHODS:
      Eight patients with asthma underwent two allergen challenges 30 minutes after
      pretreatment with CS that was inhaled from a large holding chamber at
      approximately 30 L/min or approximately 70 L/min. Percent decreases in FEV1 at a
      common dose of allergen on the two challenge days were compared. Values of skew
      (an indicator of aerosol distribution homogeneity) obtained from gamma camera
      lung images after slow and faster inhalation of radiolabeled CS were also
      compared. RESULTS: Mean (+/- SD) allergen-induced decrease in FEV1 was 5.4% +/-
      4.2% after slow inspiration of CS, which was significantly less than the allergen
      induced decrease in FEV1 after faster inhalation of CS with 12.6% +/- 11% (p <
      0.05). Mean skew values were also significantly decreased after slow inspiration
      of CS, and differences in decreases in allergen FEV1 and skew values for the two
      breathing maneuvers were significantly correlated. CONCLUSION: These data
      indicate that protection against allergen-induced asthma can be optimized by
      slowly inspiring CS from a large holding chamber compared with faster inhalation
      of the drug. These results appear to be related to enhanced distribution
      homogeneity of CS within the lungs.

PMID- 9564801
TI  - Racial differences in emergency department use persist despite allergist visits
      and prescriptions filled for antiinflammatory medications.
AB  - BACKGROUND: African-American children use the emergency department (ED) for
      asthma care more than their Caucasian counterparts. OBJECTIVE: We sought to
      compare ED utilization for asthma care by race, adjusting for prescriptions
      filled for antiinflammatory medications, type of index visit (specialist vs
      nonspecialist), and demographic variables. METHODS: An index asthma visit was
      identified for a cohort of managed care enrollees aged 4 to 11 years. Information
      on asthma encounters and drug claims data was evaluated during a prospective
      observation period of 12 months. RESULTS: African-American race was associated
      with one or more ED visits during the observation period (relative risk [RR] =
      1.8, 95% CI = 1.3 to 2.5, p < 0.01). After adjusting for index visit type,
      prescriptions filled, and selected demographic variables, African-American race
      remained associated with post-index ED utilization (adjusted RR = 1.6, 95% CI =
      1.0 to 2.4, p = 0.05). Additional findings included an inverse relationship
      between African-American race and antiinflammatory medications among children
      with nonspecialist index visits (RR = 0.5, 95% CI = 0.3 to 0.9, p = 0.02) and a
      positive relationship between African-American race and hospitalization after an
      ED visit for asthma care (RR = 10.2, 95% CI = 1.4 to 74.8, p < 0.01). CONCLUSION:
      African-American children were more likely to use ED asthma care even after
      adjusting for the type of index visit, prescriptions filled for antiinflammatory
      medications, and selected demographic variables. Racial differences in ED
      utilization for asthma care could be caused by a higher prevalence of
      uncontrolled or undertreated disease among African-American children not
      receiving specialty care.

PMID- 9564802
TI  - Immunoblotting analysis of twin sera provides evidence for limited genetic
      control of specific IgE to house dust mite allergens.
AB  - BACKGROUND: Although some studies have shown genetic control of specific IgE
      responses to purified grass allergens, studies with other allergens have not
      supported this. The extent of such control for house dust mite (HDM)
      (Dermatophagoides pteronyssinus) allergens is unclear. OBJECTIVE: We sought to
      determine the extent to which genetic factors control the specificity of IgE
      responses to individual HDM allergens by comparing the immunoblot patterns of IgE
      binding of serum from monozygotic and dizygotic members of a large cohort of
      Australian twins. METHODS: HDM proteins separated by sodium dodecylsulfate
      polyacrylamide gel electrophoresis were immunoblotted with sera from 317 twin
      pairs in which at least one twin had at least a weak HDM skin test response.
      Concordance levels for IgE binding to the individual HDM components were compared
      in the subset of 142 pairs of twins in which both twins were allergic to HDMs
      (skin prick test wheal diameter, > 3 mm). RESULTS: Over all 36 blotted bands, the
      mean case-wise concordance was 41% for monozygotic twins and 17% for dizygotic
      twins. Of the components detected, only those of molecular weights 23 kd and 16
      kd were significantly different between the groups (p < 0.01). Differences
      observed between the monozygotic and dizygotic twins could be partly explained by
      overall IgE hyperresponsiveness. CONCLUSION: Evidence for genetic control of IgE
      responses to 36 IgE-binding HDM components from a large sample of twins showed
      significant differences in concordance for two components and nonsignificant
      differences for several others. In the monozygotic twins, concordance never
      exceeded 67% for any band, and most monozygotic individuals recognized components
      their co-twin did not. Genetic control of overall atopy in monozygotic twins is
      far stronger than that controlling specific sensitization to HDM allergens.

PMID- 9564803
TI  - Immunoblot analysis of salivary allergens in 10 mosquito species with worldwide
      distribution and the human IgE responses to these allergens.
AB  - BACKGROUND: Most people develop skin reactions to mosquito bites, however, little
      is known about mosquito salivary allergens and the IgE responses to them.
      OBJECTIVES: We sought to identify these allergens and the specific IgE responses
      they elicit. METHODS: Saliva or salivary gland extracts were prepared from 10
      mosquito species, including seven species with worldwide distribution: Aedes
      (Ae.) aegypti, Ae. vexans, Ae. albopictus, Ae. togoi, Ae. triseriatus, Culex
      (Cx.) quinquefasciatus, Cx. pipiens, Cx. tarsalis, Anopheles (An.) sinensis, and
      Culiseta (Cs.) inornata. Proteins from these preparations were separated by
      sodium dodecylsulfate-polyacrylamide gel electrophoresis and transferred to
      nitrocellulose membranes, which were immunoblotted by sequential incubations with
      human serum, monoclonal anti-human IgE, and enzyme-conjugated goat anti-mouse
      IgG. Salivary allergens were analyzed by using a pooled serum from subjects
      allergic to mosquitos. Individual IgE responses to each allergen were evaluated
      in 12 subjects allergic to mosquitos living in Canada, the United States, and
      China, as well as in five subjects not allergic to mosquito bites. To study
      species-shared allergens, the membranes were immunoblotted with two rabbit
      antibodies specific to recombinant mosquito salivary proteins. RESULTS: Three to
      sixteen salivary allergens with molecular masses ranging from 16 to 95 kd were
      found in each species. Both species-shared and species-specific allergens were
      identified by molecular masses, binding to the two rabbit antibodies, and
      individual IgE responses to species indigenous to and absent from the regions
      where the subjects lived. Salivary allergens, especially from Ae. aegypti, Ae.
      vexans, and Ae. albopictus, elicited higher IgE responses in subjects allergic to
      mosquitos than in nonallergic subjects. CONCLUSIONS: Species-shared and species
      specific allergens that cause IgE responses in subjects allergic to mosquitos are
      immunologically identified. Species-shared allergens are the most important for
      potential use in diagnosis and immunotherapy.

PMID- 9564804
TI  - Effects of peptide therapy on ex vivo T-cell responses.
AB  - BACKGROUND: Peptide therapy targets T cells directly with short peptides
      containing multiple T-cell receptor epitopes. Murine studies suggest T-cell
      anergy as the mechanism of action; however, changes in T-cell cytokine profiles
      may be more relevant in human beings. OBJECTIVE: We sought to study the effects
      of peptide therapy on ex vivo antigen-specific T-cell responses. METHODS: Antigen
      specific T-cell lines were generated from subjects enrolled in a double-blind,
      placebo controlled, two-dose study of the ALLERVAX CAT therapeutic, containing
      Fel d 1 peptides (ImmuLogic Pharmaceutical Corp., Waltham, Mass.) (n = 7, 8, and
      7, respectively, for groups receiving placebo, 75 microg, or 750 microg). Each
      subject had three lines propagated before and after receiving peptide therapy;
      antigens used were cat hair extract, Fel d 1 peptides, and tetanus toxoid
      (negative control). Proliferative responses and cytokine generation from each
      line were assessed after two restimulations with antigen and autologous antigen
      presenting cells. RESULTS: The Fel d 1 peptide lines showed a dose-dependent
      decrease of IL-4 production (p = 0.02 and 0.025, respectively, for the 750 microg
      group vs both the 75 microg and placebo groups). IL-4 production from the cat
      hair allergen extract lines and interferon-gamma production from both the Fel d 1
      peptide lines and cat hair allergen extract lines showed no statistically
      significant changes. The control tetanus toxoid lines showed no changes in
      cytokine production; there were no significant changes in proliferation with any
      of the antigens in any of the treatment groups. In the clinical arm of the trial,
      only the 750 microg dose of peptides produced a significant response.
      CONCLUSIONS: Peptide therapy induces a significant, dose-dependent decrease in
      peptide-stimulated IL-4 production, consistent with either a shift in T-cell
      phenotype or peptide-specific T-cell tolerance.

PMID- 9564805
TI  - Cord blood mononuclear cells and milk-specific T-cell clones are tools to
      evaluate the residual immunogenicity of hydrolyzed milk formulas.
AB  - BACKGROUND: Hydrolyzed milk formulas (HFs) are given to infants allergic to cow's
      milk proteins and, for preventive reasons, to atopy-prone newborns for which
      breast feeding is not feasible. The ultimate properties of HFs are not only a
      reduced allergenicity but also decreased immunogenic capacity combined with good
      taste and caloric value. No information is available concerning the capacity of
      HFs to induce immune responses. OBJECTIVE: We sought to determine the residual
      immunogenic capacity of partially (pHF) and extensively hydrolyzed milk formula
      (eHF), and we studied the cellular reactivity of cord blood-derived (n = 71)
      mononuclear cells induced by 10 different HFs. METHODS: To test the effect of HF
      on T-helper cells, beta-casein-specific T-cell clones (TCCs, n = 21) from
      individuals allergic to milk were established, and T-cell proliferation and
      cytokine profiles (interferon-gamma and IL-4) were determined on stimulation with
      HF. RESULTS: We found significantly reduced proliferative responses of eHF
      compared with milk proteins. Whey-based pHF displayed the same proliferative
      capacity as unmodified milk proteins. As expected, extensively processed whey
      products displayed lower cellular responses compared with partially hydrolyzed
      products (pHF whey vs eHF whey, p < 0.0001). No difference in cellular response
      was found between casein-based pHF and casein-based eHF. Beta-casein-specific
      TCCs (n = 21) proliferated in response to casein-derived hydrolysates (14% with
      casein/whey-based pHF, 4% with casein-based pHF, and 0% with casein-based eHF).
      Whey-based pHF was also found to induce proliferation in beta-casein-specific
      TCCs, indicating the presence or the generation of peptides displaying cross
      reactivity with these whey-derived hydrolysates. TCCs stimulated with whey- or
      casein-based pHF or eHF produced the same amount of cytokines (IL-4, interferon
      gamma) as the same clones stimulated with unmodified products. CONCLUSION: Our
      data indicate that whey- and casein-derived eHFs display highly reduced
      immunogenic properties at the T-cell level. In contrast, pHFs display residual
      immunogenic properties detectable at the T-cell level, reflecting a potential for
      the induction of pathogenetically important T-cell responses.

PMID- 9564806
TI  - Antagonistic peptides specifically inhibit proliferation, cytokine production,
      CD40L expression, and help for IgE synthesis by Der p 1-specific human T-cell
      clones.
AB  - BACKGROUND: Allergic disorders are characterized by IgE antibody responses to a
      multitude of allergens as a result of the ability of these antibodies to
      specifically bind to high-affinity IgE receptors on mast cells and basophils.
      This interaction results in receptor activation and release of soluble mediators
      such as histamine and leukotrienes, which cause allergic reactions in various
      target organs. Because the synthesis of IgE is tightly regulated by cytokines and
      CD40 ligand (L) interactions, CD4+ helper T cells are obvious targets, with the
      aim to modulate allergen-induced IgE responses. OBJECTIVES: Because of the
      central role of allergen-specific T-helper type 2 (TH2) cells in the pathway
      leading to IgE synthesis in vitro and in vivo, we have evaluated the possibility
      of inhibiting allergen-induced activation of these cells by using allergen
      derived peptides that have been modified by single amino acid substitutions.
      METHODS: Three cloned human TH2-like CD4+ T-cell lines, specific for Der p 1, the
      major allergen in house dust, were used in this study. Upon activation with Der p
      1 or specific Der p 1-derived wild-type peptides, these T-cell clones produce
      high levels of IL-4 and IL-5 and low levels of interferon-gamma and IL-2,
      respectively, and furthermore give help to B cells for the production of IgE in
      vitro. Modified synthetic peptides were generated by the introduction of single
      amino acid substitutions into two different T-cell activation-inducing epitopes
      on Der p 1. The effects of these modified peptides were studied in Der p 1
      induced proliferation, cytokine production, and in vitro IgE production assays.
      RESULTS: Several substituted Der p 1-derived peptides failed to induce T-cell
      proliferation, in contrast to the native peptides. In addition, some of these
      peptides acted as antagonists by strongly inhibiting wild-type peptide-induced
      proliferation as well as the production of interferon-gamma, IL-2, IL-4, and IL
      5, although the production of the latter two cytokines was less affected than
      that of interferon-gamma, even at a 100-fold molar excess of the antagonistic
      peptides. In addition, the presence of an excess of each of the antagonistic
      peptides during the activation of Der p I-specific T-cell clones prevented
      induction of CD40L expression, resulting in a failure of these cells to give help
      to B cells for the production of IgE in vitro, even in the presence of exogenous
      IL-4. CONCLUSIONS: Substitution of certain amino acid residues in immunogenic Der
      p 1-derived peptides results in the generation of peptides that fail to induce
      proliferation of Der p 1-specific T-cell clones. In addition, these modified
      peptides have strong antagonistic activities on Der p 1-induced proliferation,
      cytokine production, and CD40L expression by allergen-specific T-cell clones as
      well as on T cell-mediated IgE production by B cells. These findings suggest that
      modified peptides interfere with allergen-induced activation of T cells,
      including the production of cytokines and the expression of surface molecules
      important for successful T cell-B cell interactions, and may therefore have
      therapeutic potential by inhibiting the expansion and function of allergen
      specific TH2 cells.

PMID- 9564807
TI  - Identification of actinidin as the major allergen of kiwi fruit.
AB  - BACKGROUND: Allergic reactions to fruits and vegetables are among the most
      frequent food allergies in adults. Kiwi fruit (Actinidia chinensis) is commonly
      involved, causing local mucosal, systemic, or both types of symptoms by an IgE
      mediated mechanism. In a previous study on 30 patients allergic to kiwi, we
      identified a major allergen of 30 kd against which all sera tested clearly
      reacted. Other allergens were detected at 12, 24, and 28 kd. OBJECTIVE: The aim
      of this study was to fully characterize the major kiwi fruit allergen of 30 kd.
      METHODS: Allergens were separated and purified by high-performance liquid
      chromatography with anion-exchange columns. The purity of the single proteins was
      checked by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and their
      allergenicity was checked by immunoblotting with a pool of sera from patients
      allergic to kiwi. The allergens were characterized by isoelectrofocusing and
      amino acid sequencing, and periodic acid-Schiff stain was used to detect
      glycoproteins. RESULTS: Proteins of 30, 28, 24, and 17 kd were purified by high
      performance liquid chromatography. IgE binding indicated the 30 kd protein, which
      showed an isoelectric point of 3.5, as the major allergen of kiwi. Determination
      of its partial amino acid sequence and comparison with the Swiss Protein Bank
      showed that this was actinidin, the main protein component of kiwi. The 24 and 28
      kd proteins had the same N-terminal sequence, which did not correspond to any
      known protein. The 17 kd protein had a blocked N-terminal sequence. CONCLUSIONS:
      These results demonstrate that the major allergen of kiwi fruit, Act c 1, is
      actinidin, a proteolytic enzyme belonging to the class of thiol-proteases. Two
      other allergens of 24 and 28 kd appear identical on amino acid sequencing.

PMID- 9564808
TI  - Interferon-gamma promotes exaggerated cytokine production in keratinocytes
      cultured from patients with atopic dermatitis.
AB  - Recent studies suggest that skin keratinocytes from patients with atopic
      dermatitis (AD) and nonatopic subjects differ in their intrinsic ability to
      respond to proinflammatory stimuli. In this study keratinocyte cultures
      established from the normal-looking skin of six adult patients with AD and six
      healthy, nonatopic control subjects were compared in their response to interferon
      (IFN)-gamma, a potent proinflammatory lymphokine whose expression is increased in
      chronic AD lesions. Basal expression of IFN-gamma receptor as well as IFN-gamma
      induced membrane expression of HLA-DR and intercellular adhesion molecule (ICAM)
      1 were evaluated by flow cytometry. Keratinocyte release of IL-1alpha, IL-1
      receptor antagonist (IL-1ra), granulocyte-macrophage colony stimulating factor
      (GM-CSF), and tumor necrosis factor (TNF)-alpha were measured by ELISA on culture
      supernatants after treatment with IFN-gamma or medium alone. Expression of
      membrane IFN-gamma receptor was similar in keratinocytes cultured from nonatopic
      subjects and subjects with AD. IFN-gamma (10 to 500 U/ml) induced comparable
      levels of membrane HLA-DR and ICAM-1 in both groups of keratinocytes. In
      contrast, spontaneous release of IL-1alpha, IL-1ra, GM-CSF, and TNF-alpha was
      increased in the supernatants of unstimulated keratinocytes from patients with AD
      compared with keratinocytes from control subjects, with IL-1ra and GM-CSF
      reaching statistically significant difference. Moreover, IFN-gamma-induced
      release of all the cytokines tested was much higher for keratinocytes from
      patients with AD, but the IL-1ra/IL-1alpha ratio for the two groups of
      keratinocytes was not substantially different, either basally or after IFN-gamma
      stimulation. The results indicate that keratinocytes from patients with AD are
      hyperresponsive to IFN-gamma in terms of cytokine release.

PMID- 9564809
TI  - CD1-restricted T-cells influence IgG subclass and IgE production.
AB  - BACKGROUND: Human CD1 has recently emerged as a third family of antigen
      presenting molecules that is distinct from either major histocompatibility
      complex class I or class II. OBJECTIVE: We investigated whether the CD1b
      restricted T-cell interaction with antigen alters human IgG subclass and IgE
      isotype production. METHODS: CD1b-restricted antigen-specific T cells derived
      from the skin lesion of a patient with leprosy were stimulated with their cognate
      antigen, lipoarabinomman (LAM) of Mycobacterium leprae, in the presence of CD1+
      antigen-presenting cells and tested for their ability to alter IgG subclass and
      IgE production from IgD+ B cells. RESULTS: CD1-restricted T cells cultured with
      CD1+ antigen-presenting cells in the absence of LAM induced IgG1, IgG3, IgG4, and
      IgE, whereas CD1b-restricted T cells cultured in the presence of LAM induced IgG1
      and IgG3 and inhibited production of IgG4 and IgE. Production of IgG4 and IgE was
      rescued in the CD1-restricted system by the addition of anti-interferon-gamma.
      IgG2 production was not induced under any circumstances. CONCLUSION: In this
      study we demonstrated that a specific CD1b-restricted T-cell line can behave
      similarly to classically-restricted Th1-type T cells. CD1b-restricted T-cells of
      this type may regulate immune responses to microbial pathogens by simultaneously
      enhancing cell-mediated immunity and downregulating IgG4 and IgE responses.

PMID- 9564810
TI  - Pneumocystis carinii pneumonia in an infant with X-linked agammaglobulinemia.

PMID- 9564811
TI  - Anaphylaxis to beans.

PMID- 9564812
TI  - Allergic vulvovaginitis induced by house dust mites: a case report.

PMID- 9564813
TI  - Intraoral and respiratory allergy to Eruca sativa (Cruciferae family) in a
      subject with sensitization to pollen allergens.

PMID- 9564814
TI  - Food allergy in a patient with adenosine deaminase deficiency undergoing enzyme
      replacement with polyethylene glycol-modified adenosine deaminase.

PMID- 9564815
TI  - Association between allergic disease and reactivity to recombinant Der p 2
      allergen of house dust mites in a tropical situation.

PMID- 9564816
TI  - Selective type-1 hypersensitivity to cefuroxime.

PMID- 9564817
TI  - Season of birth and cockroach allergen sensitization in children with asthma.

PMID- 9564818
TI  - Induced sputum examination.

PMID- 9564819
TI  - Undertreatment of bronchial asthma in a nonselected population.

PMID- 9564820
TI  - Rapid desensitization for L-asparaginase hypersensitivity.

PMID- 9564821
TI  - Antileukotrienes in chronic urticaria.

PMID- 9564822
TI  - What's in a name or what does leukemia inhibitory factor have to do with the
      pituitary gland?

PMID- 9564823
TI  - Leukemia inhibitory factor modulates interleukin-1beta-induced activation of the
      hypothalamo-pituitary-adrenal axis.
AB  - We have shown that leukemia inhibitory factor (LIF) is expressed in corticotroph
      cells and stimulates POMC gene expression and ACTH secretion in vivo and in
      vitro. We therefore examined the regulation of in vitro and in vivo pituitary LIF
      expression by cytokines known to stimulate the hypothalamo-pituitary-adrenal
      axis. In the corticotroph cell line AtT-20/D16v-F2, recombinant murine
      interleukin-1beta (IL-1beta; 0.1-10.0 ng/ml) caused a 5- to 10-fold increase in
      LIF messenger RNA (mRNA) levels. LIF mRNA expression was induced as early as 1 h,
      peaked at 2 h, and still persistently elevated above the baseline after 8 h. This
      effect of IL-1beta on LIF mRNA expression was abolished by preincubation with
      human IL-1 receptor antagonist (100 ng/ml) or antimurine IL-1beta antibody (10
      microg/ml). Tumor necrosis factor-alpha (20 ng/ml) only modestly increased LIF
      mRNA, but was synergistic with IL-1beta (up to 2.5-fold). In contrast, IL-2 and
      IL-6 did not alter LIF mRNA. In C57BL/6 mice, i.p. injection of 100 ng IL-1beta
      increased plasma ACTH and corticosterone levels after 1 h (P < 0.02). In
      addition, pituitary LIF mRNA content was increased for up to 2 h in response to
      IL-1beta. In comparison to wild-type (+/+) B6D2F1 mice, LIF knockout mice with a
      deleted LIF gene (-/-) exhibited decreased plasma ACTH (631 +/- 61 vs. 376 +/- 50
      pg/ml; P < 0.01) and corticosterone (783 +/- 85 vs. 433 +/- 51 ng/ml; P < 0.01)
      levels 1 h after i.p. IL-1beta administration. In conclusion, corticotroph LIF
      mRNA expression is specifically stimulated by IL-1beta and tumor necrosis factor
      alpha. The attenuated hypothalamo-pituitary-adrenal response to IL-1beta in LIF
      knockout mice indicates that the effect of IL-1beta on ACTH secretion is
      modulated by LIF. Thus, LIF appears to function as an immune-neuroendocrine
      modulator signaling the hypothalamo-pituitary-adrenal axis.

PMID- 9564824
TI  - Murine leukemia inhibitory factor gene disruption attenuates the hypothalamo
      pituitary-adrenal axis stress response.
AB  - Recently, we have shown that human fetal pituitary, mouse corticotroph AtT20
      cells, and murine hypothalamus and pituitary express leukemia inhibitory factor
      (LIF). LIF knockout mice (LIFKO), heterozygous and wild type (wt), of B6D2F1
      genetic background were used to examine whether LIF may play a role in the
      regulation of the hypothalamo-pituitary-adrenal axis in vivo. Resting levels of
      plasma ACTH and corticosterone were similar in all three genotypes. However,
      LIFKO mice did not respond to 30-min restraint and 45-min immobilization stress
      with increased plasma ACTH. Increased circulating ACTH was only observed in LIFKO
      mice after very short immobilization stress (15 min), but this ACTH level was
      lower than in wt animals (P < 0.05). Injection of mycobacterial adjuvant resulted
      in a 2-fold increase of corticosterone levels 7 days after treatment in wt, but
      not LIFKO, mice (P < 0.05). Pituitary POMC messenger RNA (mRNA) levels were very
      low in LIFKO animals. Although 15 and 45 min of immobilization stress resulted in
      enhanced POMC mRNA content in all three groups, this elevation was lowest in
      LIFKO mice. Injection of 12 microg murine LIF to LIFKO and normal C57BL/6 animals
      resulted in increased plasma ACTH and corticosterone levels and elevated
      pituitary POMC mRNA levels in both LIF-repleted and LIF-depleted mice. Thus, LIF
      appears to play an important role in activating the hypothalamo-pituitary-adrenal
      axis during stress and inflammation.

PMID- 9564825
TI  - Interferon-gamma inhibits the steroidogenic acute regulatory protein messenger
      ribonucleic acid expression and protein levels in primary cultures of rat Leydig
      cells.
AB  - Interferon-gamma (IFNgamma) is an immunomodulating cytokine that has profound
      effects on reproductive function. IFNgamma inhibits steroidogenesis both in vivo
      and in vitro. The mechanism by which IFNgamma inhibits Leydig cell
      steroidogenesis remains unclear. In the present study, we evaluated the effect of
      IFNgamma on the expression and regulation of the steroidogenic acute regulatory
      protein (StAR) gene in primary cultures of rat Leydig cells. StAR facilitates the
      efficient production of steroid hormone by regulating the translocation of
      cholesterol from the outer to the inner mitochondrial membrane, the site of the
      cytochrome P450 side-chain cleavage (P450scc) enzyme system that converts
      cholesterol to pregnenolone. IFNgamma inhibited hCG-induced StAR messenger RNA
      (mRNA) levels in a dose-dependent manner. The addition of IFNgamma in a
      concentration of 500 U/ml decreased hCG-induced 3.8- and 1.7-kilobase StAR mRNA
      by 78% and 70%, respectively. IFNgamma also reduced hCG-stimulated P450scc mRNA
      levels by 69%. The inhibitory effects of IFNgamma on StAR mRNA levels were
      confirmed by ribonuclease protection assay. As early as 12 h after the addition
      of IFNgamma, hCG-induced StAR mRNA levels decreased by more than 44%. To evaluate
      the effects of IFNgamma on StAR protein levels, Western blot analyses were
      performed. hCG in a concentration of 10 ng/ml increased StAR protein by 5.6-fold.
      Treatment of Leydig cells with IFNgamma (500 U/ml) decreased hCG-induced StAR
      protein by 44%. In contrast, interleukin-1 and murine tumor necrosis factor-alpha
      reduced hCG-induced P450scc mRNA expression without inhibiting StAR mRNA or
      protein levels. In conclusion, IFNgamma inhibits Leydig cell steroidogenesis by
      down-regulating StAR gene expression and protein production.

PMID- 9564826
TI  - Antiprogestins suppress basal and activin-stimulated follicle-stimulating hormone
      secretion in an estrogen-dependent manner.
AB  - Previous studies from our laboratory, demonstrating that suppression of serum FSH
      by RU486 requires a high estrogen (E) background, suggested that E-inducible
      progesterone receptors play a role in the regulation of FSH secretion. We
      demonstrated further that the type II antiprogestin RU486 and the type I
      antiprogestin ZK98299 both suppressed the elevated serum FSH and FSHbeta
      messenger RNA levels similarly on the evening of proestrus, but had divergent
      effects on the morning of estrus, when only RU486, but not ZK98299, lowered the
      elevated serum FSH level (secondary FSH surge). In the present work we used
      primary anterior pituitary cell culture to examine whether RU486 caused direct, E
      dependent suppression of basal and recombinant human activin A (activin)-induced
      FSH secretion in the gonadotrope and to compare this direct effect, if any, with
      that of ZK98299. Primary cell cultures were prepared from anterior pituitaries
      collected from cycling female rats either on metestrous or proestrous morning and
      cultured in DMEM, supplemented with charcoal-stripped serum without or with 10 nM
      estradiol (E2) for 96 h; exposure to test agents occurred during the last 48 h of
      culture. FSH released into the medium and intracellular FSH content were
      determined by RIA. In cells from the anterior pituitary of metestrous rats
      cultured in E2-free medium, neither antiprogestin (10 nM) affected FSH release;
      in contrast, when cells were cultured in medium to which E2 had been added, both
      antiprogestins caused profound suppression of both basal and activin (10 ng/ml)
      stimulated FSH release. In cell cultures from proestrous rats, both
      antiprogestins caused a slight, but significant, suppression of basal FSH release
      even in the absence of added E2; activin-stimulated FSH release, however, was not
      affected. Upon exposure of the cells from proestrous rats to E2, the
      antiprogestins potently suppressed both basal and activin-stimulated FSH
      secretion. Because the foregoing incubations were performed in culture medium
      devoid of progesterone (P4), the actions of the antiprogestins on FSH secretion
      were independent of the natural ligand. Addition of P4 (10 nM) to the cell
      cultures stimulated basal and activin-induced FSH release more in the presence
      than in the absence of E2. The FSH response to P4 was completely blocked by both
      antiprogestins in both the absence and presence of E2. Finally, both RU486 and
      ZK98299 blocked the stimulatory effect of corticosterone (1 microM) on FSH
      secretion. The observed effects of P4 and antiprogestins were specific for FSH
      secretion; LH secretion was not similarly suppressed by either antiprogestin, but
      was, in fact, stimulated by ZK98299 in E2-treated cells. We conclude that 1) E2
      inducible progesterone receptors interact with activin-mediated signal
      transduction to regulate FSH secretion, and 2) unlike on the morning of estrus in
      vivo, RU486 and ZK98299 affect FSH secretion similarly in the gonadotrope in
      vitro.

PMID- 9564827
TI  - Iodothyronine deiodinase activities in fetal rat tissues at several levels of
      iodine deficiency: a role for the skin in 3,5,3'-triiodothyronine economy?
AB  - Iodothyronine deiodinases, types I, II, and III (D1, D2, and D3) activities were
      measured in tissues of fetal rats, at 18 and 21 days of gestation, at several
      levels of iodine deficiency (ID): mild ID diet (MID) and moderately severe ID,
      MID + 0.005% perchlorate (MID+P). D2 was present in fetal skin, increased between
      days 18 and 21, and also in MID and MID+P. In skin, D3 increased during ID at day
      18, whereas there was a decrease at day 21. Skin T4 decreased in MID and MID+P,
      showing an inverse relationship with D2. Skin T3 decreased at day 18 in MID and
      MID+P but increased at day 21, probably because of the increased D2 and decreased
      D3, maintaining T3 concentrations. No effect of ID was observed on hepatic D1. D2
      increased in brain and brown adipose tissue at day 21 in MID+P. No changes were
      found in maternal placental D2 and D3, but D2 and D3 increased in the fetal
      placenta at day 18 in MID+P. A higher level of D2 is present in fetal skin than
      in the brain. As the activity is increased, in even mild ID (and already at 18
      days) it can be concluded that skin D2 is likely to be of considerable
      physiological importance, at least for fetal thyroid hormone economy, by
      contributing to the intracellular T3 content of the skin and, possibly, to the
      plasma T3.

PMID- 9564828
TI  - Luteinizing hormone-releasing hormone-signal transduction and stathmin
      phosphorylation in the gonadotrope alphaT3-1 cell line.
AB  - We have investigated the effects of GnRH (LHRH) and of the protein kinase C (PKC)
      activator 12-O-tetradecanoylphorbol-13-acetate on stathmin phosphorylation in the
      gonadotrope alphaT3-1 cell line. Stathmin expression and its phosphorylation were
      maximal during the exponential phase of cell growth. LHRH stimulated stathmin
      phosphorylation through a specific receptor in a dose- and time-dependent manner,
      and TPA induced a similar extensive stathmin phosphorylation. Their effects were
      inhibited either in PKC-depleted alphaT3-1 cells, or by the PKC inhibitor
      staurosporine. In the context of the known implication of PKC in LHRH-induced
      signal transduction, our results show that stathmin phosphorylation is involved
      in LHRH transduction, either as a result of direct activation of specific PKC
      isoforms or through a pathway involving kinases downstream to PKC activation.

PMID- 9564829
TI  - Thecal cell-granulosa cell interactions involve a positive feedback loop among
      keratinocyte growth factor, hepatocyte growth factor, and Kit ligand during
      ovarian follicular development.
AB  - Interactions between mesenchymal-derived thecal cells and epithelial-derived
      granulosa cells are essential for follicular development in the ovary. These
      mesenchymal-epithelial cell interactions are in part mediated by keratinocyte
      growth factor (KGF), hepatocyte growth factor (HGF), and Kit ligand (KL). This
      study investigates the hypothesis that thecal cell-derived growth factors (e.g.
      KGF and HGF) regulate granulosa cell function, and granulosa cell-derived growth
      factors (e.g. KL) regulate thecal cell function. Gonadotropin regulation of this
      cell-cell interaction is also examined. Sensitive quantitative RT-PCR assays were
      used to analyze gene expression of KGF, HGF, and KL in the ovary. Thecal cell
      derived KGF and HGF stimulated KL expression in bovine granulosa cells. Granulosa
      cell-derived KL stimulated KGF and HGF expression in bovine thecal cells. These
      results suggest that thecal and granulosa cells interact in a positive feedback
      loop mediated by KGF, HGF, and KL. Previous studies have suggested that
      gonadotropins (i.e. FSH and LH) regulate locally produced growth factor
      expression in the ovary. Treatment of bovine granulosa cells with FSH and hCG (a
      LH agonist) directly stimulated KL expression. The LH agonist hCG was also found
      to stimulate both KGF and HGF expression in thecal cells. The actions of
      gonadotropins on follicular development may in part be indirectly regulated by
      KL, KGF, and HGF expression. A novel positive feedback loop was identified
      between thecal cells and granulosa cells that is mediated by KL, KGF, and HGF.
      Thecal cell-derived KGF and HGF can stimulate granulosa cell-derived KL
      expression, and KL, in turn, can stimulate thecal cell-derived KGF and HGF
      expression. Combined observations support the hypothesis that mesenchymal
      epithelial cell interactions between thecal and granulosa cells can play a
      significant role during ovarian follicular development and mediate gonadotropin
      actions.

PMID- 9564830
TI  - Arginine vasopressin triggers intracellular calcium release, a calcium-activated
      potassium current and exocytosis in identified rat corticotropes.
AB  - Arginine vasopressin (AVP) stimulates the secretion of ACTH from pituitary
      corticotropes. We investigated the action of AVP in single corticotropes of male
      rats. Corticotropes were identified with the reverse hemolytic plaque assay using
      antibodies against ACTH. Using the whole-cell recording technique in conjunction
      with the fluorescent Ca2+ indicator, indo-1 to measure the concentration of
      cytosolic free Ca2+ ([Ca2+]i), we show that AVP triggers a transient and plateau
      pattern of Ca2+ signal. The [Ca2+]i elevation activates the apamin-sensitive Ca2+
      activated K+ current, which, in turn, causes membrane hyperpolarization. The Ca2+
      signal can be elicited in the absence of extracellular Ca2+ and is mimicked by
      intracellular inositol 1,4,5-trisphosphate (IP3). Both GDP-beta-S and heparin
      inhibit the AVP response. Thus, AVP triggers intracellular Ca2+ release from the
      (IP3)-sensitive store via a GTP binding protein-coupled phosphoinositide pathway.
      Using the high temporal resolution capacitance measurement to detect exocytosis
      in single corticotropes, we show that a burst of exocytosis is evoked during the
      AVP-triggered [Ca2+]i elevation. Exocytosis can also be triggered when Ca2+ is
      released directly from the IP3-sensitive store via flash photolysis of caged IP3.
      We conclude that AVP-stimulated ACTH secretion in rat corticotrophs is closely
      coupled to intracellular Ca2+ release from the IP3-sensitive store.

PMID- 9564831
TI  - Novel sites of adrenomedullin gene expression in mouse and rat tissues.
AB  - Adrenomedullin (AM) was originally identified in pheochromocytoma tissue and was
      characterized as a hypotensive peptide. The tissue distribution and cellular
      localization of AM messenger RNA (mRNA) were determined in mouse and rat tissues
      by in situ hybridization. Three probes were used: two nonoverlapping probes to
      the pro-AM N-terminal 20 peptide (PAMP) and AM peptide regions of mouse pro-AM,
      and a larger complementary DNA (cDNA) probe spanning both the PAMP- and AM
      peptide-coding regions. The most intense expression of AM mRNA was in endometrium
      and epithelial cells lining the uterus and mouse adrenal medulla. Moderate levels
      of expression were detected in kidney glomerulus and cortical distal tubules,
      ovarian corpus luteum and follicles, epithelial cells lining the bronchioles,
      cardiac atrium and ventricle, posterior pituitary (particularly in female rats),
      stomach, small intestine (microvilli, mucosa and submucosa), spleen, and
      pancreas. Lower levels were observed in pulmonary alveoli, anterior pituitary,
      and submandibular gland. No expression was detected in the testis, thymus,
      skeletal muscle, or liver. The localization of AM mRNA in epithelial cells lining
      the uterus, bronchioles, and gastrointestinal tract indicates novel roles for AM,
      possibly as an antimicrobial agent. The strong expression of AM in uterus, ovary,
      and posterior pituitary suggests that AM plays a role in female reproduction.

PMID- 9564832
TI  - Evidence for inhibition by protein kinase A of receptor/G alpha(q)/phospholipase
      C (PLC) coupling by a mechanism not involving PLCbeta2.
AB  - The effects of cAMP on the oxytocin-stimulated increase in phosphatidylinositide
      turnover and the possible pathways involved were investigated in a human
      myometrial cell line (PHM1-41) and in COS-M6 cells overexpressing the oxytocin
      receptor. Preincubation with chlorophenylthio-cAMP (CPT-cAMP), forskolin, or
      relaxin inhibited oxytocin-stimulated phosphatidylinositide turnover in PHM1-41
      cells, and the inhibition was reversed by H-89, a relatively specific protein
      kinase A inhibitor. Both CPT-cAMP and transiently expressed protein kinase A
      catalytic subunit inhibited stimulation by oxytocin and carbachol of [3H]inositol
      1,3,4-trisphosphate formation in COS-M6 cells expressing oxytocin or muscarinic
      M1 receptors, respectively. CPT-cAMP also inhibited phosphatidylinositide
      turnover stimulation by endothelin-1 in PHM1-41 cells, further demonstrating the
      generality of the cAMP-inhibitory mechanism. Since G betagamma activation of
      phospholipase Cbeta2 (PLCbeta2) is a suggested target of protein kinase A, the
      possibility that the oxytocin receptor couples to PLCbeta2 via G alpha(i)G
      betagamma activation was explored. Western blot analysis of PHM1-41 cells and COS
      M6 cells detected PLCbeta1 and PLCbeta3, but not PLCbeta2. In PHM1-41 cells,
      pertussis toxin reduced the oxytocin-stimulated increase in [3H]inositol 1,3,4
      trisphosphate by 53%, and this was reversed completely by H-89. Thus, the
      inhibitory effect of pertussis toxin may result from an indirect effect of cAMP
      elevation. These data suggest that receptor/G alpha(q)-coupled stimulation of
      PLCbeta1 or PLCbeta3 can be inhibited by cAMP through a phosphorylation mechanism
      involving protein kinase A that does not involve PLCbeta2. In smooth muscle, this
      mechanism could constitute potentially important cross-talk between pathways
      regulating contraction and relaxation.

PMID- 9564833
TI  - Effect of 17beta-estradiol on somatostatin receptor expression and inhibitory
      effects on growth hormone and prolactin release in rat pituitary cell cultures.
AB  - In the present study, we tested whether 17beta-estradiol (E2)-induced PRL
      sensitivity to somatostatin-14 (SRIF) involves selective up-regulation of
      discrete somatostatin receptor subtypes (ssts) in primary cultures of female rat
      pituitary cells. The efficacy of the endogenous peptide SRIF to inhibit GH and
      PRL secretion and cAMP accumulation was compared with those of octreotide (OCT),
      BIM-23052, BIM-23056, and BIM-23268, which have been reported to be relatively
      selective for rat sst2, sst3, and sst5. Experiments were performed in steroid
      depleted media supplemented or not with 1 nM E2 for 96 h. SRIF, OCT, and BIM
      23052 inhibited cAMP accumulation and GH release independently of E2. In
      contrast, all three agonists affected PRL release in E2-treated cultures only.
      Inhibition of cAMP accumulation by SRIF, OCT, and BIM-23052 was enhanced by
      exposure of cells to E2. The rank of potency of the agonists, OCT = SRIF > BIM
      23052, was similar for GH and PRL inhibition. BIM-23268 was a weak agonist on GH,
      but not on PRL, secretion. BIM-23056 had no effect on the release of either
      hormone, but slightly inhibited cAMP formation in E2-treated cells. To verify
      whether SRIF receptor gene expression correlated with these observations,
      messenger RNA (mRNA) transcripts corresponding to the five ssts were measured by
      quantitative RT-PCR in the presence or absence of E2. Control cells expressed
      predominantly sst2 and sst3 transcripts; sst1 mRNA was present in moderate
      amounts, whereas sst4 and sst5 were only weakly expressed. E2 had a differential
      effect on distinct ssts; it increased mRNA concentrations corresponding to sst2
      and sst3, and decreased that of sst1. These results indicate that sst2 and sst3
      receptors are the major somatostatin receptors expressed in the female rat
      pituitary, and that both of them are positively regulated by estradiol. However,
      the capacity of lactotropes to respond to SRIF after exposure to E2 seems to
      depend more upon E2-induced up-regulation of the sst2 than of the sst3 receptor
      subtype.

PMID- 9564834
TI  - In vivo and in vitro evidence for the involvement of tumor necrosis factor-alpha
      in the induction of leptin by lipopolysaccharide.
AB  - To examine the role of tumor necrosis factor-alpha (TNF alpha) in mediating
      leptin secretion during an immunological challenge, we studied the effects of
      lipopolysaccharide (LPS) and TNF alpha on leptin secretion in endotoxin-sensitive
      C3H/HeOuJ (OuJ) mice, endotoxin-insensitive C3H/HeJ (HeJ) mice, and primary
      adipocytes cultured from both. Intraperitoneal injection of LPS increased plasma
      concentrations of TNF alpha and leptin in OuJ mice, but not in HeJ mice,
      suggesting a causal relationship between the induction of TNF alpha and leptin.
      Consistent with this idea, i.p. injection of recombinant murine TNF alpha
      increased plasma leptin in both OuJ and HeJ mice. To determine whether TNF alpha
      induces leptin secretion by acting directly on fat cells, primary adipocytes from
      OuJ and HeJ mice were cultured in the presence of TNF alpha or LPS. Whereas LPS
      was without effect on leptin secretion by adipocytes, TNF alpha induced a marked
      increase in the cell supernatant leptin concentration. These data demonstrate
      that TNF alpha plays a role in regulating the increase in leptin caused by LPS.
      Moreover, they show that TNF alpha can act directly on adipocytes to stimulate
      leptin secretion. Our results are consistent with the emerging view that leptin
      is a key hormone coupling immune system activity to energy balance.

PMID- 9564835
TI  - A biphasic developmental pattern of circulating leptin in the male rhesus macaque
      (Macaca mulatta).
AB  - To help elucidate the physiological role of leptin during somatic and sexual
      maturation, circulating concentrations of leptin were measured in 36 male rhesus
      monkeys of ages ranging from 0-20 yr. The body weight of these animals showed a
      steady increase of approximately 1 kg/yr during the first decade of life and
      reached a plateau at approximately 13 yr. In contrast, serum leptin
      concentrations showed a biphasic developmental pattern, which was highlighted by
      a strong negative correlation with body weight (r = -0.74, P < 0.001) before the
      onset of puberty (at approximately 3.5 yr) and by a strong positive correlation
      afterward (r = 0.77, P < 0.001). Overall, the developmental changes in serum
      leptin concentrations closely mimicked the expected developmental changes in
      serum testosterone concentrations (r = 0.62, P < 0.001), which were highly
      elevated at birth, fell to basal levels during the juvenile phase of development,
      and gradually rose again after the initiation of puberty. However, mean serum
      leptin concentrations during the peripubertal period itself (3-5 yr) were
      significantly lower (P < 0.01) than those observed during the first year of life
      or those observed in fully mature adults (i.e. > 7 yr) (3.5 +/- 0.3, 1.4 +/- 0.2,
      and 3.3 +/- 0.6 ng/ml, respectively). These data demonstrate that the role of
      leptin in energy homeostasis of primates is more than a simple linear
      relationship, being highly dependent upon the developmental age. Furthermore, the
      data do not support the hypothesis that leptin plays a major role in triggering
      the onset of puberty in primates, although the strong correlation between serum
      concentrations of leptin and testosterone suggests that the secretion of these
      two hormones may be causally linked.

PMID- 9564836
TI  - Insulin-like growth factor II promoter expression in cultured rodent osteoblasts
      and adult rat bone.
AB  - Insulin-like growth factor (IGF)-II stimulates bone formation by increasing the
      replication of cells of the osteoblastic lineage and by enhancing the
      differentiated function of the osteoblast. Although IGF-II is synthesized by
      skeletal cells, little is known about the mechanisms involved and its regulation
      by growth factors. IGF-II expression is tissue specific and is developmentally
      regulated. In the present study, we examined the expression of IGF-II in fetal
      rat, newborn mouse and MC3T3-E1 osteoblastic (Ob) cells, and in adult rat
      calvariae. We also determined mechanisms involved in the regulation of IGF-II by
      platelet-derived growth factor (PDGF) BB, fibroblast growth factor-2 (FGF-2), and
      transforming growth factor (TGF) beta1. Northern analysis revealed IGF-II
      transcripts of 3.6 and 1.2 kb in osteoblastic cells and adult rat calvariae.
      Ribonuclease (RNase) protection assay using probes specific to the three known
      IGF-II promoters, P1, P2, and P3, demonstrated messenger RNA (mRNA) expression
      driven by P3 in osteoblasts and adult rat calvariae, but no expression of P1 or
      P2 transcripts. PDGF BB, FGF-2, and TGF beta1 inhibited the expression of IGF-II
      P3 mRNA by 50%. PDGF BB, FGF-2, and TGF beta1 also decreased the rates of IGF-II
      transcription in rat Ob cells as determined by nuclear run-on assays and did not
      modify the decay of IGF-II in transcriptionally arrested rat Ob cells. In
      conclusion, the synthesis of IGF-II in osteoblastic cells and in adult rat
      calvariae is driven by IGF-II P3 and is regulated by skeletal growth factors
      acting at the transcriptional level using the IGF-II P3.

PMID- 9564837
TI  - Regulation of cyclooxygenase-2 and prostaglandin F synthase gene expression by
      steroid hormones and interferon-tau in bovine endometrial cells.
AB  - Estradiol (E2) and progesterone are responsible for regulating PG synthesis in
      the endometrium during the estrous cycle and interferon-tau (IFN-tau) alters PG
      synthesis during early pregnancy in ruminants. In this study, we examined the
      effects of these steroid hormones and recombinant bovine IFN-tau (rbIFN-tau) on
      PG production and on cyclooxygenase-2 (COX-2) and PG F (PGF) synthase (PGFS) gene
      expression in isolated endometrial cells. E2 decreased both PGF2alpha and PG E2
      (PGE2) whereas progesterone increased PGF2alpha secretion in epithelial cells.
      Steroid hormones had no effect on PG production in stromal cells. rbIFN-tau
      attenuated both PGF2alpha and PGE2 production in epithelial cells and enhanced
      their production, and the ratio of PGE2 to PGF2alpha, in stromal cells. Northern
      blot analysis showed that E2 and rbIFN-tau decreased COX-2 messenger RNA (mRNA)
      levels in epithelial cells. Conversely, rbIFN-tau increased COX-2 mRNA in stromal
      cells. Furthermore, rbIFN-tau decreased PGFS mRNA in both cell types and this was
      associated with the increase in PGE2/PGF2alpha ratio. These results show that the
      regulation of PG synthesis by steroid hormones is different in endometrial
      epithelial and stromal cells in vitro. The attenuation of PGF2alpha secretion
      from epithelial cells and increased PGE2 production in stromal cells by rbIFN-tau
      are modulated by steroid hormones.

PMID- 9564838
TI  - Regulation of major histocompatibility (MHC) class II human leukocyte antigen-DR
      alpha gene expression in thyrocytes by single strand binding protein-1, a
      transcription factor that also regulates thyrotropin receptor and MHC class I
      gene expression.
AB  - The single strand binding protein (SSBP-1) is a positive regulator of TSH
      receptor gene expression and binds to an element with a GXXXXG motif. The S box
      of the mouse major histocompatibility class II gene has multiple GXXXXG motifs
      and can also bind SSBP-1. The S box is one of four highly conserved elements on
      the 5'-flanking region of class II genes that are necessary for interferon-gamma
      (IFNgamma) to overcome the normally suppressed state of the gene and induce
      aberrant class II expression. In this report we show that SSBP-1, when
      overexpressed in FRTL-5 thyroid cells, is a positive regulator of human leukocyte
      antigen (HLA)-DR alpha class II gene expression, as is IFNgamma or the class II
      trans-activator (CIITA). This is evidenced by increased exogenous promoter
      activity, increased endogenous RNA levels, and increased endogenous antigen
      expression after transfecting full-length SSBP-1 complementary DNA together with
      a HLA-DR alpha promoter-reporter gene chimera into TSH-treated FRTL-5 thyroid
      cells whose endogenous SSBP-1 levels are low. IFNgamma reverses the ability of
      TSH to decrease endogenous SSBP-1 RNA levels. Also, whereas SSBP-1 transfection
      does not cause any increase in IFNgamma-induced exogenous promoter activity,
      transfection of SSBP-1 and CIITA additively increases endogenous class II RNA
      levels to levels measured in cells treated with IFNgamma. Further, competition
      studies show that SSBP-1 binding is necessary for formation of the double strand
      protein/DNA complexes that are seen in electrophoretic mobility shift assays when
      the class II 5'-flanking region is incubated with extracts from IFNgamma-treated
      FRTL-5 cells and that have been previously associated with IFNgamma-induced
      aberrant class II expression. These data suggest that SSBP-1 is involved in the
      action of IFNgamma to overcome the normally suppressed state of the class II
      gene; it functions together with CIITA, whose expression is independently
      increased by IFNgamma. The effect of SSBP-1 as a positive regulator of class II
      promoter activity is lost in cells maintained without TSH, in which endogenous
      SSBP-1 RNA levels are already high in the absence of aberrant class II gene
      expression. These data suggest that high levels of endogenous SSBP-1 are
      insufficient to cause aberrant class II expression, but, rather, TSH or IFNgamma
      treatment additionally modulates the cell, albeit differently, such that
      transfected or endogenous SSBP-1, respectively, can express its positive
      regulatory activity. The effect of TSH is consistent with reports indicating that
      TSH enhances the ability of IFNgamma to increase class II gene expression despite
      the fact IFNgamma increases endogenous SSBP-1 to only the same levels as in cells
      untreated with TSH. Finally, the effect of SSBP-1 as a positive regulator is lost
      when GXXXXG motifs, which exist on both the coding and noncoding strands of the S
      box, are mutated. Consistent with this, mutation and oligonucleotide competition
      studies show that GXXXXG motifs are necessary for either strand of the S box to
      bind protein/DNA complexes containing SSBP-1 in FRTL-5 cell extracts or to bind
      to recombinant SSBP-1. They also suggest that the SSBP-1-binding sites on either
      strand of the HLA-DR alpha S box are functionally distinct. We conclude from
      these data that the positive regulatory action of SSBP-1 on class II gene
      expression involves GXXXXG motifs on each strand of the highly conserved S box of
      the class II 5'-flanking region. As SSBP-1 is modulated by IFNgamma and is
      involved in class I and TSH receptor as well as class II gene expression in FRTL
      5 cells, the sum of the data supports the hypotheses that common transcription
      factors regulate all three genes, and their altered activities may contribute to
      the development of autoimmunity.

PMID- 9564839
TI  - Elevated expression of lanosterol 14alpha-demethylase (CYP51) and the synthesis
      of oocyte meiosis-activating sterols in postmeiotic germ cells of male rats.
AB  - Mammalian CYP51 encodes lanosterol 14alpha-demethylase (P45014DM) that is
      involved in the postsqualene part of cholesterol biosynthesis. This enzyme
      removes the 14alpha-methyl group from lanosterol and 24,25-dihydrolanosterol
      producing intermediates in cholesterol biosynthesis, the oocyte meiosis
      activating sterols FF-MAS and MAS-412. Human and rat CYP51 messenger RNAs (mRNAs)
      are expressed in all tissues, with highest levels in the testis due to the
      presence of an additional shorter CYP51 transcript in this tissue. In situ
      hybridization shows the highest CYP51 mRNA levels in seminiferous tubules, with
      only background levels in Leydig cells. The rat testis-specific CYP51 mRNA arises
      from the use of an upstream polyadenylation site and is restricted to germ cells,
      being most abundant in elongating spermatids in stages VII-XIV, whereas somatic
      CYP51 transcripts are present in all cells. In contrast, the mRNA levels of
      squalene synthase are maximal in round spermatids, and no germ cell-specific
      transcript is observed. The rat male germ cell-specific CYP51 transcript is
      translated in vitro to two proteins of approximately 55 and 53.5 kDa. CYP51
      activity is higher in protein extracts of testes and germ cells of sexually
      mature rats than in prepubertal animals, in which postmeiotic germ cells are not
      yet present. This shows increased capacity for the production of MAS sterols by
      male germ cells that have already completed meiosis, suggesting that they serve a
      role different from meiosis activation.

PMID- 9564840
TI  - The dipsogenic effects of rat relaxin: The effect of photoperiod and the
      potential role of relaxin on drinking in pregnancy.
AB  - Experiments were done to examine whether rat relaxin is dipsogenic and whether
      such dipsogenic effects of rat relaxin are related to time of injection during
      the light-dark cycle. Female rats were fitted with a chronic intra-cerebro
      ventricular (i.c.v.) cannula. Rat relaxin (2.5, 5, 10, 25, 50, or 100 ng/2 microl
      in 0.9% saline) was injected into the right lateral ventricle at either morning
      (0800-1000 h), afternoon (1400-1600 h), or night (2200-2400 h), and water
      consumption was measured. Relaxin caused a dose-dependent dipsogenesis at doses >
      or = 5 ng, but the sensitivity and magnitude of the response varied with the
      photoperiod. Water consumption was smallest (3.5 +/- 0.7 ml at 50 ng) and least
      sensitive (minimal effective dose at 25 ng) in the afternoon and maximal (17.7 +/
      2.3 ml at 50 ng) and most sensitive (minimal effective dose 5 ng) at night. The
      latency from injection to drinking was 55.8 +/- 10.4 sec (mean +/- SEM) and did
      not vary significantly with either the dose or time of day. A second set of
      experiments was done to examine the effects of neutralizing the central actions
      of relaxin on drinking behavior in pregnancy. Pregnant rats were injected daily,
      through a chronically implanted i.c.v. cannula, with either a specific monoclonal
      antibody raised against rat relaxin from day 12 to day 22 of gestation or with
      saline as a control. Drinking and eating behavior and weight gain were monitored
      every 12 h during pregnancy. There was a significant decrease in water consumed
      at night, but no effect on drinking during the day in relaxin-neutralized rats.
      These animals also showed a decrease in weight gain during pregnancy compared
      with controls and gave birth to lighter-weight litters. These data provide
      evidence that the dipsogenic response to exogenous rat relaxin in female rats
      varies with time of injection during the light-dark cycle and suggest that
      relaxin in the brain may have a role in nighttime drinking behavior during the
      second half of pregnancy.

PMID- 9564841
TI  - Antisense TR3 orphan receptor can increase prostate cancer cell viability with
      etoposide treatment.
AB  - In androgen-responsive LNCaP human prostatic cancer cells, human TR3 orphan
      receptor, a member of the steroid receptor superfamily, can be rapidly induced by
      androgen. In contrast, ablation of androgen by castration can induce the
      expression of the TR3 orphan receptor gene in rat ventral prostate that has
      undergone apoptosis. This phenomenon prompted us to further analyze the potential
      role of human TR3 orphan receptor in prostate cancer cells in which apoptosis had
      been induced. Northern blot analysis shows that human TR3 orphan receptor
      expression can be induced rapidly after treatment of LNCaP and PC-3 prostate
      cancer cells with calcium ionophore or etoposide. Our data further demonstrate
      that a much higher concentration of etoposide was needed to kill the same number
      of cells in LNCaP and PC-3 cells transfected stably with antisense TR3 orphan
      receptor compared with that in control vector transfectants. Together, our data
      suggest that the human TR3 orphan receptor may play an important role in
      modulating drug-induced prostate apoptosis.

PMID- 9564843
TI  - Effects of growth hormone, activin, and follistatin on the development of
      preantral follicle from immature female mice.
AB  - The aim of this study was to investigate whether GH and insulin-like growth
      factor I (IGF-I) are involved in preantral folliculogenesis and, if so, to
      clarify the relationship between GH/IGF-I and activin/follistatin (FS) systems in
      immature female mice. Ovaries were obtained from 11-day-old mice, and preantral
      follicles, 100-105 microm in diameter, were mechanically isolated and selected
      for culture. Ten preantral follicles per well were cultured with different
      quantities and combinations of additives as follows: no additives (control),
      recombinant human FSH (rhFSH), IGF-I, recombinant human GH (rhGH), activin A, and
      recombinant human FS (rhFS). Mean diameters of the follicles were measured daily,
      and estradiol and immunoreactive inhibin levels in the cultured medium were
      assayed by RIA on day 4. rhGH showed stimulatory effects on the follicular
      diameter and the secretion of estradiol and immunoreactive inhibin. These effects
      were augmented by the presence of IGF-I and activin A. IGF-I alone did not show
      any stimulatory effect. The addition of rhFSH to activin A or to rhGH and activin
      A promoted preantral follicular growth and hormone production. On the other hand,
      GH- or activin-stimulated follicular growth was suppressed by rhFS in a dose
      dependent manner. These results indicate that activin A and rhGH may play an
      important role in controlling earlier phases of follicular development during the
      infantile period, which is considered to be gonadotropin independent.

PMID- 9564842
TI  - ROR alpha gene expression in the perinatal rat cerebellum: ontogeny and thyroid
      hormone regulation.
AB  - Deficiency of thyroid hormone (TH) during the perinatal period results in severe
      neurological abnormalities in rodent cerebellar development. However, the
      molecular mechanisms of TH action in the developing cerebellum are not fully
      understood. Of note, a mutant mouse, staggerer, in which the orphan nuclear
      hormone receptor ROR alpha gene is disrupted, exhibits cerebellar abnormalities
      similar to those seen in the hypothyroid animals, despite normal thyroid
      function. We, therefore, speculated that TH (tetraiodo-L-thyronine; T4) may
      regulate ROR alpha gene expression, which then may regulate genes essential for
      normal brain development. To test this hypothesis, we studied the changes in ROR
      alpha gene expression in perinatal hypothyroid rat cerebellum and the effect of
      TH replacement using Northern blot analysis, ribonuclease protection assay and in
      situ hybridization histochemistry. During cerebellar development, an
      approximately 3-fold increase in the cerebellar content of ROR alpha messenger
      RNA (mRNA) was seen in both propylthiouracil-treated, and propylthiouracil
      treated and T4-replaced animals. However, the increase was accelerated when T4
      was injected, although the ROR alpha mRNA content was identical, with or without
      T4, by 30 days after birth (P30). In contrast, T4 treatment suppressed the TH
      receptor alpha1 and c-erbA alpha2 mRNA content by P30; retinoic acid X receptor
      beta mRNA content was not influenced by thyroid status. A significant
      hybridization signal for ROR alpha mRNA was seen only over Purkinje cells in the
      cerebellar cortex by in situ hybridization histochemistry. These results indicate
      that TH alters the timing of expression of the ROR alpha gene in the Purkinje
      cells of the cerebellar cortex, which may, in turn, influence Purkinje cell
      differentiation.

PMID- 9564844
TI  - Expression of melanocortin-5 receptor in secretory epithelia supports a
      functional role in exocrine and endocrine glands.
AB  - Melanocortins (alphaMSH and ACTH-related peptides) influence the physiological
      functions of certain peripheral organs, including exocrine and endocrine glands.
      This study was designed to determine the identity and anatomical localization of
      the melanocortin receptors (MC-R) expressed in these organs in the rat. MC5-R
      messenger RNA was found in exocrine glands, including lacrimal, Harderian,
      preputial, and prostate glands and pancreas, as well as in adrenal gland,
      esophagus, and thymus, as demonstrated by ribonuclease protection assays. In
      exocrine glands, MC5-R messenger RNA expression was restricted to secretory
      epithelia. MC-R protein was likewise present in secretory epithelia of exocrine
      glands, as determined by 125I-labeled [Nle4,D-Phe7]alphaMSH ([125I]NDP-MSH)
      binding and autoradiography in tissue sections. Specific [125I]NDP-MSH binding
      was also observed in adrenal cortex, thymus, spleen, and esophageal and
      trachealis muscle. MC receptors in these sites are accessible to circulating MC-R
      agonists in vivo, as specific binding of [125I]NDP-MSH was observed in exocrine
      and adrenal glands after systemic injection in vivo. Taken together, these
      findings show that the MC5 receptor is commonly and selectively expressed in
      exocrine glands and other peripheral organs. Based on these findings and
      compelling evidence from other studies, a functional coherence is suggested
      between central and peripheral actions of melanocortins and melanocortin
      receptors in physiological functions, including thermoregulation,
      immunomodulation, and sexual behavior.

PMID- 9564845
TI  - Regulation of insulin-like growth factor-binding protein-5 by insulin-like growth
      factor I and interleukin-1alpha in ovine articular chondrocytes.
AB  - Insulin-like growth factors (IGFs) contribute to the maintenance of the cartilage
      matrix by stimulating proteoglycan synthesis. In contrast, interleukin-1 (IL-1),
      an inflammatory cytokine, suppresses the synthesis of proteoglycans. In
      pathological conditions the chondrocytes' responsiveness to IGF-I is decreased,
      and elevated levels of IGF-binding proteins (IGFBPs) have been implicated as a
      possible cause. The aim of this study was to investigate the effects of IGF-I and
      IL-1 on IGFBP production by ovine articular chondrocytes (OAC) and the roles of
      these IGFBPs in the regulation of proteoglycan synthesis. As revealed by Western
      ligand and immunoblotting, OACs secreted IGFBP-2 and a 24-kDa IGFBP in culture
      medium under basal conditions. Exposure of the cells to IGF-I for 48 h resulted
      in the appearance of IGFBP-5 in the medium. Des(1-3)IGF-I, an IGF-I analog with
      reduced affinity for IGFBPs, also increased the level of IGFBP-5, but to a lesser
      extent than IGF-I, whereas LR3IGF-I, which has virtually no affinity for IGFBPs,
      had no effect on IGFBP-5. Furthermore, IGFBP-5 underwent a time-dependent limited
      proteolysis when incubated with OAC-conditioned medium, degrading into 22- and 16
      kDa fragments. The degradation of IGFBP-5 was significantly inhibited by IGF-I,
      but not by des(1-3)IGF-I or LR3IGF-I. Basic fibroblast growth factor,
      transforming growth factor-beta, and platelet-derived growth factor had no effect
      on OAC IGFBPs. However, IL-1alpha increased the IGFBP-5 level in a dose-dependent
      manner, showing maximum activity at 200 U/ml. Furthermore, IL-1alpha, but not IGF
      I, induced IGFBP-5 messenger RNA expression, as assessed by Northern blot
      analysis. Coincubation of IGF-I with IL-1alpha resulted in a substantially
      increased IGFBP-5 protein level, suggesting a synergism between the mechanisms of
      action of these two factors. Des(1-3)IGF-I and LR3IGF-I were 10 times more potent
      than IGF-I in stimulating proteoglycan synthesis, indicating inhibition of IGF-I
      activity by endogenous IGFBPs. IL-1alpha reduced the IGF-I bioactivity, but had
      no effect on the activities of the IGF-I analogs, thus implying that locally
      produced IGFBPs, particularly IGFBP-5, which was substantially increased when IGF
      I and IL-1alpha were coincubated, mediated the reduction of the IGF-I activity.
      Our results demonstrate that IGF-I and IL-1alpha synergistically increase the
      level of IGFBP-5 in OAC by inhibiting the proteolysis and stimulating the
      expression of IGFBP-5, respectively. Furthermore, the attenuation of IGF-I
      stimulated proteoglycan synthesis by IL-1alpha in OAC appears to be mediated by
      chondrocyte IGFBPs. We conclude that locally produced IGFBPs, in particular IGFBP
      5, may play a critical role in the regulation of cartilage matrix degradation in
      inflammatory and degenerative arthritides.

PMID- 9564847
TI  - Amelioration of diabetes in nonobese diabetic mice with advanced disease by
      linomide-induced immunoregulation combined with Reg protein treatment.
AB  - Oral linomide, (quinoline-3-carboxamide), has been shown to prevent autoimmune
      insulitis, islet destruction, and diabetes in NOD mice treated at an early stage
      of the disease, but confers only partial protection in animals with advanced
      disease. Reg protein, the gene product of a complementary DNA isolated from a
      regenerating rat islet library, has been previously shown to induce expansion of
      beta-cell mass in pancreatectomized rats. To determine the effect of treatment
      combining immunomodulation and Reg protein on advanced autoimmune diabetes, we
      treated female NOD mice with oral linomide and i.p. Reg protein injections. In 14
      week-old animals with less severe disease (glucose tolerant), treatment with each
      agent alone resulted in amelioration of diabetes, as did treatment with Reg alone
      in 5-week-old prediabetic mice. In 14-week-old animals with more severe disease
      (glucose intolerant), only treatment with the combination of both agents, but not
      that with each separately, resulted in amelioration of diabetes. Our study
      suggests that treatment aimed at abrogation of autoimmunity combined with
      expansion of beta-cell mass constitutes a potential therapeutic approach for
      treatment of insulin-dependent diabetes mellitus.

PMID- 9564846
TI  - Glucagon-like peptide-1-(7-36)amide increases pulmonary surfactant secretion
      through a cyclic adenosine 3',5'-monophosphate-dependent protein kinase mechanism
      in rat type II pneumocytes.
AB  - Glucagon-like peptide-1 (GLP-1) receptor messenger RNA has been identified in
      cells considered type II pneumocytes that are involved in the synthesis and
      secretion of the pulmonary surfactant. In an attempt to open new insights into
      the control of surfactant secretion, we studied the effects of glucagon-related
      peptides in this process. Accordingly, type II pneumocytes were isolated from
      Wistar rat lungs and cultured overnight with [methyl-14C]choline, and then the
      basal and stimulated secretions of [14C]phosphatidylcholine were measured. GLP
      1(7-36)amide stimulated phosphatidylcholine secretion in a concentration
      dependent manner in the 1-100 nM range; the concentration of the peptide that
      produced a half-maximal response was 10 nM. Exendin-4 induced similar effects. No
      changes were observed when GLP-1-(1-37), GLP-2, or exendin-(9-39) was added to
      the medium. However, the latter reversed the stimulatory effects of GLP-1-(7
      36)amide and exendin-4. A study of the mechanism through which GLP-1-(7-36)amide
      exerts its stimulatory effect was carried out using different agents that are
      well known stimulants of phosphatidylcholine secretion. GLP-1-(7-36)amide did not
      produce any change in the stimulatory effect observed with terbutaline or 8-bromo
      cAMP, suggesting the involvement of a cAMP-dependent protein kinase in the
      stimulatory effect of this peptide on phosphatidylcholine secretion. It was
      further supported by the use of inhibitors of protein kinases and by the
      stimulation of cAMP production in type II pneumocytes incubated with either GLP-1
      (7-36)amide or exendin-4.

PMID- 9564848
TI  - Effect of interleukins on UGT2B15 and UGT2B17 steroid uridine diphosphate
      glucuronosyltransferase expression and activity in the LNCaP cell line.
AB  - Cytokines are known to modulate the level of both phase 1 and phase 2 drug
      metabolizing enzymes in hepatocytes. Although the effects of cytokines on
      cytochrome P450 (CYP450) enzymes are well understood, there is limited knowledge
      on how cytokines may affect steroid UDP-glucuronosyltransferase (UGT) phase 2
      enzyme activity and expression in different cell types, including hepatocytes and
      steroid target cells. LNCaP cells, which is a human prostate cancer cell line, is
      a good model to study the effect of cytokines in steroid target cells because it
      is known to express steroidogenic enzymes, including UGT2B15 and UGT2B17, which
      are widely expressed steroid UGT enzymes known to conjugate androgens. In this
      study, we examined the possible interaction among interleukin-1alpha (IL-1alpha),
      IL-4, IL-6, and steroid UGT enzymes (UGT2B15 and UGT2B17). Treatment of LNCaP
      cells with IL-1alpha led to a dose-dependent inhibition of dihydrotestosterone
      (DHT) glucuronidation. IL-1alpha decreased both UGT activity and LNCaP cell
      proliferation in the absence and presence of DHT (0.5 nM); a maximal inhibition
      of 70% was observed. IL-6 inhibited LNCaP cell proliferation as well as the DHT
      induced proliferation of these cells. However, neither IL-4 nor IL-6
      significantly affected the formation of DHT glucuronide. Ribonuclease protection
      and Western blot analyses demonstrated a specific reduction of UGT2B17 transcript
      and protein levels in IL-1alpha-treated LNCaP cells. The level of UGT2B15 was not
      affected by cytokine treatments, indicating a differential regulation between
      these two UGT enzymes. Transfection experiments performed with the UGT2B17 gene
      promoter region indicates that the regulation occurs at the transcription level
      via putative cis-acting elements. This study indicates that cell proliferation
      and UGT expression in steroid-responsive cancer cells are differentially
      regulated depending on the cytokines present in the cell microenvironment.

PMID- 9564849
TI  - Differential dose-dependent effects of epidermal growth factor on gene expression
      in A431 cells: evidence for a signal transduction pathway that can bypass Raf-1
      activation.
AB  - Epidermal growth factor (EGF), which plays an important role in normal and
      tumoral cell growth regulation, displays an ambivalent dose-dependent effect on
      the proliferation of epithelial cells overexpressing EGF receptor. However, the
      underlying molecular mechanisms remain obscure. In this study we have examined
      the regulation of amphiregulin (AR) gene expression by growth inhibitory (10(-9)
      M) and stimulatory (10(-12) M) EGF concentrations in A431 cells. The time course
      of AR messenger RNA (mRNA) accumulation was different with 10(-12) and 10(-9) M
      EGF; AR induction by 10(-9) M EGF peaked between 1 and 1.5 h, then decreased to
      the basal level within 2 h. Conversely, the induction by 10(-12) M EGF was
      slightly delayed, but persisted for 4 h. The involvement of tyrosine
      phosphorylation in AR induction by EGF was suggested by the ability of the
      tyrosine phosphatase inhibitor sodium orthovanadate to prolong AR expression
      induced by 10(-12) or 10(-9) M EGF. In the presence of the protein phosphatase 2A
      inhibitor, okadaic acid, 10(-9) M EGF induced a persistent accumulation of AR
      mRNA. On the contrary, okadaic acid abrogated the stimulation of AR mRNA level
      induced by a low EGF concentration, suggesting that both EGF concentrations
      activated distinct regulatory mechanisms. The signaling components involved in
      the differential activities of EGF in A431 cells were then examined. We
      previously reported a relationship between the ambivalent activity of EGF and the
      p42-mitogen-activated protein (MAP) kinase activity. Thus, 10(-12) M EGF induced
      a sustained MAP kinase activation, whereas 10(-9) M EGF led to a sharp, but
      transitory, activation. The MAP kinases are activated by MAP kinase kinases (MEK1
      and MEK2). Whereas no significant effect of 10(-12) M EGF could be detected, 10(
      9) M EGF was shown to activate MEK1 and, to a lesser extent, MEK2. Also, both MAP
      kinase activation and AR induction by 10(-9) M, but not by 10(-12) M, EGF were
      inhibited by the MEK1 inhibitor PD98059. Moreover, the involvement of c-Raf-1 in
      the signaling pathway induced by EGF was verified. A concentration of 10(-9) M
      EGF induced stimulation of c-Raf-1 kinase activity, whereas 10(-12) M EGF not
      only failed to activate c-Raf-1, but led to a moderate decrease in its kinase
      activity. These results demonstrate that in EGF receptor-overexpressing cells,
      EGF may differently affect gene expression and cell proliferation through
      distinct mechanisms of regulation.

PMID- 9564851
TI  - Pancreatic hormone expression in the murine thymus: localization in dendritic
      cells and macrophages.
AB  - The expression of preproinsulin (ppIns), proglucagon, prosomatostatin, and
      propancreatic polypeptide was investigated in thymic extracts, thymic cells, and
      thymic cell lines from C57BL/6 mice by RT-PCR. The expression of pancreatic
      hormones was similar in thymic extracts taken from neonatal and 2-, 4-, and 8
      week-old animals, but was decreased in 20-week-old animals. Pancreatic hormone
      expression was not observed in mouse liver, salivary gland, or spleen. Analysis
      of thymic cell populations revealed a 10- to 20-fold enrichment in expression of
      all hormones in low buoyant density cells. No expression was detected in high
      buoyant density cells (predominantly thymocytes) or in thymic epithelial cell
      lines, primary cultures of epithelial cells, or peripheral macrophages. In
      addition, immunoreactive insulin, measured by specific RIA, was detectable in the
      low buoyant density population, but not in high buoyant density cells. The
      enriched cell population was depleted of contaminating lymphocytes and sorted
      based on reactivity to the cell surface markers F4/80 (macrophage) or N418
      (dendritic cells). Cells gated for N418 demonstrated expression for ppIns, but
      not the other pancreatic hormones. Conversely, expression for proglucagon,
      prosomatostatin, and propancreatic polypeptide, but not ppIns, was detected in
      F4/80-gated cells. Our data indicate that pancreatic endocrine hormones are
      differentially expressed by dendritic cells and macrophages in a normal mice.

PMID- 9564850
TI  - Guanosine triphosphatase-activating protein-associated protein, but not src
      associated protein p68 in mitosis, is a part of insulin signaling complexes.
AB  - The insulin receptor, following insulin stimulation of cells, triggers formation
      of various signaling complexes. In rat HTC hepatoma cells overexpressing normal
      human insulin receptors (HTC-IR), p85 regulatory subunit of phosphatidylinositol
      3-kinase (PI3K) forms signaling complexes containing the insulin receptor,
      insulin receptor substrate 1 (IRS-1), guanosine triphosphatase-activating protein
      (GAP) and 60-70 kDa phosphotyrosine proteins (p60-70). In the present study, we
      demonstrate that p60-70 interacts directly with the p85 subunit via src homology
      2 domain of the latter. Employing antibodies specific to two p85 isoforms,
      p85alpha and p85beta, we demonstrate that HTC-IR cells express both p85 isoforms,
      and these isoforms induce the formation of similar signaling complexes in
      response to insulin. p60-70, present in both alpha-p85alpha and alpha-p85beta
      immunoprecipitates, is a GAP-associated protein, but is distinct from the p68 src
      associated protein in mitosis (Sam68) by several criteria. These data suggest
      that 1) GAP-associated protein, but not Sam68, is a part of insulin signaling
      complexes; and 2) p85alpha and p85beta form similar, but distinct, insulin
      receptor signaling complexes.

PMID- 9564853
TI  - Cytokine regulation of the rat proopiomelanocortin gene expression in AtT-20
      cells.
AB  - Although cytokines are known to be involved in the regulation of ACTH secretion,
      their effects, along with the molecular mechanisms, on POMC gene expression are
      not thoroughly characterized. In this study we examined the effects of
      representative cytokines on transcription of the POMC gene in corticotrophs in
      vitro using AtT20PL, a clone of the AtT20 cell line stably transfected with
      approximately 0.7 kilobase of the rat POMC 5'-promoter-luciferase fusion gene. In
      each experiment, cells were incubated with the cytokine tested, and the changes
      in POMC 5'-promoter activity were determined by a luciferase assay. The results
      showed that interleukin-1beta (IL-1beta) stimulated promoter activity in a
      biphasic manner [weak short term effects (2-3 h) followed by potent long term
      effects (>12-16 h)]. Tumor necrosis factor-alpha had similar effects, but much
      less potency. IL-6 showed a profound stimulatory, but only a long term (>20 h),
      effect. IL-2 did not influence POMC expression. In contrast, interferon-alpha
      (IFN alpha) and IFN-gamma showed acute stimulatory effects (approximately 4 h)
      followed by marked inhibitory effects (>8 h). Although the acute effects of IL
      1beta, IL-6, and tumor necrosis factor-alpha alone were minimal, they
      significantly potentiated the stimulatory effect of CRH on POMC expression.
      Finally, pretreatment of the cells with a broad spectrum tyrosine kinase
      inhibitor, genistein, abolished or significantly diminished the effects of all
      cytokines except IFNs. Our results suggest that 1) each cytokine tested has a
      distinct effect on POMC gene expression; 2) there are positive cross-talk effects
      between CRH and cytokines at the corticotroph level; and 3) tyrosine
      phosphorylation cascades are involved in the intracellular signaling mechanisms
      of some cytokines.

PMID- 9564852
TI  - Pituitary-adrenocortical responses to persistent noxious stimuli in the awake
      rat: endogenous corticosterone does not reduce nociception in the formalin test.
AB  - Although glucocorticoids inhibit inflammation and are used to treat painful
      inflammatory rheumatic diseases, the contribution, if any, of endogenous
      pituitary-adrenocortical activity to the control of pain remains unclear. We
      report that injection of dilute formalin into the hindpaw not only evokes
      inflammation and pain-related behavior, but it also increases ACTH and
      corticosterone to a greater extent than restraint and saline injection alone.
      This difference was particularly robust during the final periods of pain-related
      behavior in the formalin test, when the ACTH and corticosterone (B) levels in the
      restraint/saline control group had returned to normal. These results indicate
      that formalin-evoked increases in ACTH and B reflect nociceptive input, rather
      than the stress associated with handling. To test the hypothesis that the
      formalin-induced increase in corticosterone reduces pain and inflammation, we
      next evaluated the effect of adrenalectomy (to prevent activation of
      glucocorticoid receptors) or high-dose dexamethasone (to saturate glucocorticoid
      receptors) on nociceptive processing in the formalin test. Neither adrenalectomy
      nor dexamethasone changed behavioral or cardiovascular nociceptive responses.
      Furthermore, the increases in blood pressure and heart rate produced by formalin
      may not be mediated by adrenomedullary catecholamine release. In addition, we
      conclude that the nociceptive component of the formalin stimulus is sufficient to
      activate the pituitary-adrenocortical system in the awake rat, but that the
      resulting release of corticosterone does not feed back and reduce nociceptive
      processing.

PMID- 9564854
TI  - Inhibition of mitogen-activated protein kinase activity and proliferation of an
      early osteoblast cell line (MBA 15.4) by dexamethasone: role of protein
      phosphatases.
AB  - Chronic glucocorticoid therapy causes rapid bone loss and clinical osteoporosis.
      We found that although the glucocorticoid, dexamethasone, stimulated osteoblast
      maturation, it also inhibited proliferation of a preosteoblastic cell line, MBA
      15.4. The dexamethasone-induced decline in preosteoblast proliferation correlated
      with a 30-40% reduction in protein kinase C/TPA-stimulated mitogen-activated
      protein kinase (MAPK) activity. These steroid effects only became evident after 6
      24 h treatment, implying that dexamethasone acts on de novo synthesis of
      proteins. Because MAPK is inactivated by dephosphorylation of tyrosine and
      threonine residues, cells were treated concomitantly for 24 h with dexamethasone
      and inhibitors of tyrosine (sodium orthovanadate) and/or serine/threonine
      phosphatases (sodium fluoride). MAPK activity and cell proliferation were
      restored when MBA-15.4 cells were treated with vanadate, suggesting that
      dexamethasone up-regulates tyrosine phosphatase activity. Inactivation of
      serine/threonine phosphatases with sodium fluoride had no effect. Inhibition of
      the PKA pathway (which is growth inhibitory in mature osteoblasts) with H-89 did
      not reverse the effects of dexamethasone. Pretreatment with dexamethasone
      inhibited both peak- and extended activation plateau-phases of MAPK activity.
      Both phases were fully restored by pretreatment with vanadate, implicating more
      than one tyrosine phosphatase. Cycloheximide, alone or in combination with
      dexamethasone, prevented drop-off from plateau to basal levels, suggesting that
      an inducible dual-specificity phosphatase regulates the plateau-phase. We
      conclude that dexamethasone may inhibit preosteoblast growth via a novel tyrosine
      phosphatase pathway.

PMID- 9564855
TI  - Differential expression of the estrogen receptors alpha and beta in the rat
      corpus luteum of pregnancy: regulation by prolactin and placental lactogens.
AB  - Estradiol, together with PRL and placental lactogens, regulates steroidogenesis
      and cell hypertrophy in the rat corpus luteum of pregnancy. Although binding
      experiments have demonstrated the presence of estrogen-binding sites, no evidence
      exists as to whether the rat corpus luteum of pregnancy expresses the estrogen
      receptor (ER) genes. In this investigation, we have analyzed the expression of
      the two ER genes (ER alpha and ER beta) (by RT-PCR and in situ hybridization) in
      the rat corpus luteum, studied their developmental changes throughout pregnancy,
      and investigated the regulation of ER alpha and ER beta messenger RNA (mRNA)
      expression by PRL and placental lactogens. The RT-PCR studies showed that both ER
      mRNA species (ER alpha and ER beta) are coexpressed in the rat corpus luteum
      during pregnancy. Whereas ER alpha mRNA increased from early pregnancy, reached a
      maximum at midpregnancy, and had a remarkable decline before parturition; ER beta
      mRNA remained constant throughout pregnancy, with a significant decline at
      parturition. Examination of ER alpha and ER beta mRNA expression at the cellular
      level, by in situ hybridization, showed ER alpha expressed in both follicles and
      corpus luteum, with maximal expression at midpregnancy. In parallel with the RT
      PCR studies, ER beta mRNA was similarly expressed throughout pregnancy in the
      corpus luteum, but it was less abundant when compared with small and growing
      follicles. Western blot analysis revealed two ER immunoreactive proteins in the
      nuclear fraction obtained from pregnant rat corpus luteum: a 67-kDa moiety,
      highly expressed at midpregnancy but barely detectable in early and late
      gestation; and a 61-kDa form that remained developmentally unchanged.
      Hypophysectomy, performed early in pregnancy, induced a sharp decline in ER alpha
      mRNA expression but a less-marked reduction in ER beta mRNA levels. PRL treatment
      reverted the inhibition induced by hypophysectomy in both receptor subtypes. When
      primary luteinized cells were used to test the effect of PRL, rat placental
      lactogen I, and rat placental lactogen II on the expression of ER alpha and ER
      beta mRNA, all these lactogenic hormones stimulated both ER mRNA species in a
      dose-dependent manner. The regulation of ER mRNA expression was further evaluated
      in a luteal cell line, termed GG-CL, which apparently expresses only the ER beta
      mRNA species. Culture of the GG-CL cells, in the presence of PRL, resulted in a
      dose-related up-regulation of ER beta mRNA expression. In addition, PRL treatment
      enhanced the binding activity of GG-CL cell nuclear proteins to a classical
      estrogen response element. Furthermore, in these cells, estradiol treatment
      induced a dose-dependent up-regulation of the mRNA encoding protein kinase C
      delta isoform, a well-known estrogen target gene in the corpus luteum of the
      pregnant rat.

PMID- 9564856
TI  - Identification of cis-acting deoxyribonucleic acid elements that mediate
      gonadotropin-releasing hormone stimulation of the rat luteinizing hormone beta
      subunit gene.
AB  - GnRH plays a critical role in reproductive development and function by regulating
      the biosynthesis and secretion of the pituitary gonadotropins, LH and FSH.
      Although it is known that GnRH induces gonadotropin subunit gene transcription,
      the mechanism by which this occurs has not been elucidated. Studies have been
      hindered by the lack of available cell lines that express the LH and FSH subunit
      genes and respond to GnRH. We have transfected the rat pituitary GH3 cell line
      with the rat GnRH receptor complementary DNA. These cells, when cotransfected
      with regulatory regions of the LH or FSH subunit genes fused to a luciferase
      reporter gene, respond to GnRH with an increase in promoter activity comparable
      to that seen in primary rat pituitary cells. In this study, we have used this
      cell model to identify cis-acting elements of the LHbeta gene that mediate
      stimulation by GnRH. Analysis of a series of 5'-deletion and internal deletion
      constructs has revealed two regions of the rat LHbeta gene promoter involved in
      mediating the response to GnRH, region A (-490/-352) and region B (-207/-82).
      Fusion of region A upstream of a heterologous minimal promoter linked to the
      luciferase gene conferred GnRH responsiveness to the promoter, whereas region B
      did not. However, the presence of both regions A and B conferred a greater GnRH
      response than region A alone. Electrophoretic mobility shift assay revealed the
      presence of a protein(s) binding to region A using GH3 as well as alphaT3-1
      nuclear extracts. Thus, region A (-490/-352) confers GnRH responsiveness to the
      LHbeta subunit gene and binds to a protein(s) present in pituitary cell lines.
      DNA sequences in region B (-207/-82) also contribute to GnRH responsiveness. The
      identification of putative GnRH response elements in the rat LHbeta gene promoter
      will aid in elucidation of the mechanisms of regulation of gene expression by
      GnRH.

PMID- 9564857
TI  - Function of galanin in the anterior pituitary of estrogen-treated Fischer 344
      rats: autocrine and paracrine regulation of prolactin secretion.
AB  - Estrogen is a robust stimulator of galanin synthesis and secretion in the
      anterior pituitary. Galanin is colocalized in lactotrophs in the estrogen-treated
      anterior pituitary, and its roles in lactotroph function are still being
      elucidated. In the present studies, we quantified the phenotypes of estrogen
      treated Fischer 344 rat anterior pituitary cells expressing the galanin gene by
      dual in situ hybridization. The total population of galanin-positive pituitary
      cells increased from undetectable levels to 16% of all cells after 2 weeks of
      estrogen treatment. More than 90% of the galanin-positive cells coexpressed PRL
      messenger RNA, and one-third of the lactotrophs expressed galanin messenger RNA.
      We hypothesized that galanin in the anterior pituitary may contribute to the
      heterogeneous secretion of PRL, and that one of the functions of galanin is to
      regulate PRL secretion in an autocrine/paracrine manner. To test this hypothesis,
      we performed the reverse hemolytic plaque assay combined with in situ
      hybridization to measure PRL secretion and galanin gene expression within the
      same individual cells. PRL secretion from galanin-positive lactotrophs was
      significantly greater than that from galanin-negative lactotrophs. Moreover,
      treatment with galanin antiserum significantly attenuated PRL secretion from
      galanin-positive cells, and treatment with galanin significantly enhanced PRL
      secretion from galanin-negative lactotrophs. In conclusion, these data provide
      direct evidence that galanin derived from the estrogen-treated anterior pituitary
      stimulates PRL secretion in both autocrine and paracrine manners.

PMID- 9564858
TI  - Conversion of thyrotropin heterodimer to a biologically active single-chain.
AB  - TSH and the gonadotropins, FSH, LH, and CG are a family of heterodimeric
      glycoprotein hormones composed of a common alpha-subunit noncovalently linked to
      a hormone specific beta-subunit. Assembly of alpha- and beta-subunits is
      essential for hormone-specific posttranslational modifications, receptor binding,
      and bioactivity. Structure-function studies of TSH and gonadotropins using site
      directed mutagenesis can often affect folding, assembly, and secretion of the
      hormone. To circumvent these difficulties, recently, the gonadotropin
      heterodimers were converted to single chains. Here we converted the hTSH
      heterodimer to a biologically active single chain by genetically fusing the amino
      terminal end of the common alpha-subunit to the carboxyl terminal end of hTSHbeta
      in the presence or absence of hCGbeta carboxyl terminal peptide (CTP), which was
      used as a linker. Wild-type hTSH and the single chains were expressed in Chinese
      hamster ovary (CHO) cells, and they were efficiently secreted. Although the
      secretion rate of the single chain was 3-fold higher than that of hTSH wild-type.
      Moreover, the secretion of the single chain in the presence of the CTP linker was
      dramatically increased. On the other hand, receptor binding and in vitro
      bioactivity of the single chains were similar to that of hTSH wild-type. These
      data indicate the potential of the single chain approach to further investigate
      structure-function relationships of TSH.

PMID- 9564859
TI  - Termination of lactation induces apoptosis and alters the expression of the Bcl-2
      family members in the rat anterior pituitary.
AB  - After lactation, there is a massive loss of pituitary lactotrophs. The aim of
      this study was to investigate the events and mechanisms involved in the
      remodeling of the anterior pituitary after termination of lactation. Animals were
      analyzed at day 7 of lactation and at 4 and 7 days after pup removal. Field
      inversion gel electrophoresis was used to detect high-molecular-weight DNA
      fragments, a characteristic feature of apoptosis. Bax and Bcl-2, proteins
      involved in regulation of cell survival, were studied by immunohistochemistry and
      Western blot analysis. In addition, the expression of Bax, Bcl-2, Bcl-X(L), and
      p53 messenger RNA (mRNA) was analyzed by in situ hybridization. Four days after
      termination of lactation, a peak in high-molecular-weight DNA fragments and an
      increase in Bax, along with a decrease in Bcl-2 proteins, were observed, in
      comparison with lactation and with 7 days post lactation. The mRNAs for Bax and
      p53 also were increased, whereas no changes were detected in Bcl-2 and Bcl-X(L)
      mRNA levels. In summary, these findings indicate that the cell remodeling of the
      anterior pituitary, after the termination of lactation, occurs through the
      process of apoptosis and involves changes in Bax, Bcl-2, and p53.

PMID- 9564861
TI  - Structural determinants of cortisol resistance in the guinea pig glucocorticoid
      receptor.
AB  - The guinea pig exhibits resistance to glucocorticoids in vivo which results from
      the guinea pig glucocorticoid receptor (GR) having a lower affinity for cortisol
      than the human GR. Cloning of the guinea pig GR has revealed that the amino acid
      sequence of the ligand-binding domain (LBD) differs from the human GR at 24
      residues. The present study confirms that the decreased sensitivity and binding
      affinity of the guinea pig GR are conferred in vitro by the LBD. Further, the
      substitutions in the LBD do not confer altered relative steroid sensitivity or
      selectivity compared with the human GR. The altered sensitivity and binding of
      dexamethasone are confined to the first third of the LBD, which contains 5
      nonconservative substitutions in a region that is otherwise highly conserved
      across several species of GR. These residues, either alone or in combination,
      were targeted for site-directed mutagenesis in both the human and guinea pig LBD.
      Trans-activation studies with these mutant GR failed to exclusively implicate or
      exclude any of the residues in the observed resistance. Rather, the changes, with
      1 exception, caused a decrease in sensitivity, suggesting that critical
      intramolecular interactions involving at least 4 of these residues determine the
      correct conformation of this region. Recent molecular modeling of the GR LBD
      structure suggests that although the above region is not part of the core ligand
      binding pocket, it is required to maintain the conformation of the binding
      pocket.

PMID- 9564860
TI  - The third intracellular loop of the rat gonadotropin-releasing hormone receptor
      couples the receptor to Gs- and G(q/11)-mediated signal transduction pathways:
      evidence from loop fragment transfection in GGH3 cells.
AB  - The GnRH receptor (GnRH-R) belongs to the rhodopsin/beta-adrenergic family of G
      protein-coupled receptors. The intracellular domains of these receptors,
      particularly the regions closest to the plasma membrane in intracellular loops 2
      (2i) and 3 (3i) as well as some regions located in the membrane-proximal end of
      the COOH-terminus, are frequently important sites for G protein coupling and
      specificity determination. Although studies in mouse and human GnRH-R have
      identified loop 2i as a critical determinant for coupling the receptor to the
      G(q/11)-mediated signal transduction pathway, given the functional similarity
      among the members of this particular G protein-coupled receptor subfamily and the
      fact that the GnRH-R lacks the typical intracellular COOH-terminal domain of its
      superfamily (a potential site for G protein coupling), we investigated the
      possibility that loop 3i of this receptor also participates in GnRH-R coupling to
      G proteins. GGH(3)1' cells, a pituitary-derived cell line that expresses a
      functional rat GnRH-R coupled to both Gs and G(q/11) proteins, were transiently
      transfected with a plasmid DNA containing a complementary DNA (cDNA) coding for
      the entire loop 3i of the GnRH-R as well as with other expression plasmids
      containing cDNAs encoding loop 3i of other Gs-, G(i/o)-, or G(q/11)-coupled
      receptors. The effects of coexpression of these loops with the wild-type GnRH-R
      on inositol phosphate (IP) production, cAMP accumulation, and PRL release were
      then examined. Transfection of GGH(3)1' cells with the cDNA for loop 3i of the
      rat GnRH-R (efficiency, 35-45%) maximally inhibited buserelin-stimulated IP
      turnover by 20% as well as cAMP accumulation and PRL secretion by 30%. This
      attenuation in cellular responses to a GnRH agonist was statistically significant
      (P < 0.05) compared with the responses exhibited by GGH(3)1' cells transfected
      with a control plasmid and stimulated with the same GnRH agonist. Transfection of
      minigenes coding for loop 3i of the M1Ach-muscarinic and the alpha1B-adrenergic
      (G(q/11)-coupled) receptors resulted in 25-55% inhibition of maximal GnRH-evoked
      IP turnover. Paradoxically, loop 3i from the M1Ach-muscarinic receptor also
      maximally inhibited GnRH agonist-stimulated cAMP accumulation and PRL release by
      40% (both effects mediated through activation of the Gs protein). Transfection of
      loop 3i from the D1A -dopamine receptor (coupled to the Gs protein) produced a
      selective attenuation (40%) in Gs-mediated cellular responses. In contrast,
      receptor/G protein coupling appeared unaffected by expression of loop 3i domains
      derived from two receptors coupled to G(i/o) proteins (M2Ach-muscarinic and
      alpha2A-adrenergic receptors). These data indicate that the third intracellular
      loop of the rat GnRH-R is involved in receptor G(q/11) protein coupling and/or
      selectivity, and in the GGH(3)1' cell line, this loop is also involved in signal
      transduction mediated through the Gs protein pathway.

PMID- 9564862
TI  - Comparison of the effects of the new orally active antiestrogen EM-800 with ICI
      182 780 and toremifene on estrogen-sensitive parameters in the ovariectomized
      mouse.
AB  - The nonsteroidal antiestrogen EM-800 is approximately 10-fold more potent than
      ICI 182 780, the most potent known steroidal antiestrogen, at inhibiting estrone
      stimulated uterine weight in ovariectomized mice (half-maximal inhibitory daily
      s.c. doses of 0.2 and 2.0 microg, respectively). At maximal doses, however, both
      compounds lead to a similar maximal 90% inhibition of estrone-stimulated uterine
      weight. A 10-fold higher activity of EM-800 compared with ICI 182 780 was also
      observed on estrone-stimulated vaginal weight, with maximal inhibitions of 96%
      and 90%, respectively, achieved by the two compounds. In addition, EM-800
      injected s.c. or administered orally led to a marked loss of uterine and vaginal
      estrogen receptor levels measured by binding assay, whereas ICI 182 780 exerted
      no inhibitory effect on this parameter under the experimental conditions used.
      Comparable effects were observed when estrogen receptor protein levels were
      measured by enzyme immunoassay. After oral administration, EM-800 exerted maximal
      83% and 88% inhibitions of uterine and vaginal weight, respectively, whereas
      maximal inhibitions limited to 51% and 67% were achieved with toremifene. This
      limited inhibition by toremifene of the stimulatory effect of estrone on uterine
      and vaginal weight is probably due to the intrinsic estrogenic activity of the
      compound. The present data also show that the steroidal antiestrogen ICI 182 780
      has less than 3% the activity of EM-800 when administered by the oral route. In
      fact, EM-800 administered orally is 2- to 3-fold more potent than ICI 182 780
      injected s.c.

PMID- 9564863
TI  - Expression and hormonal regulation of coactivator and corepressor genes.
AB  - Steroid/thyroid/retinoid receptors are members of the nuclear receptor
      superfamily and ligand-inducible transcription factors. These receptors modulate
      transcription of various cellular genes, either positively or negatively, by
      interacting with specific hormone-response elements located in the target gene
      promoters. Recent data show that nuclear receptors enhance or inhibit
      transcription by recruiting an array of coactivator and corepressor proteins to
      the transcription complex. We examined and compared the expression of four
      coactivator (steroid receptor coactivator-1 and E1A-associated 300-kDa protein)
      and corepressor (SMRT and N-CoR) genes in a number of tissues including several
      endocrine glands and cell lines. We also addressed whether their messenger RNA
      levels are hormonally regulated by studying the effects of thyroid hormone (T3)
      and estrogen (E2) treatment in rat pituitary cells (GH3) in vitro and in anterior
      pituitary in vivo. Our studies show that there are distinct tissue-specific
      expression patterns of these genes. We show that T3 and E2 regulate the
      expression of steroid receptor coactivator-1 messenger RNA in the anterior
      pituitary in addition to a gender-related difference. These tissue variations may
      have physiological implications for heterogeneity of hormone responses that are
      observed in normal and malignant tissues.

PMID- 9564865
TI  - Lack of effect of leptin on glucose transport, lipoprotein lipase, and insulin
      action in adipose and muscle cells.
AB  - The effect of leptin on glucose transport, lipogenesis, and lipoprotein lipase
      activity was studied in cultured rat adipocytes and 3T3-L1 adipocytes. Leptin had
      no effect on basal and insulin stimulated glucose transport in isolated
      adipocytes from the rat and the genetically obese mouse. The incorporation of
      glucose into lipids was also unaffected. Lipoprotein lipase (LPL) activity
      remained unchanged in response to leptin in these cells, as well as in minced
      adipose tissue. Leptin also had no effect on both basal and insulin-stimulated
      glucose transport in cultured rat and human skeletal muscle cells. These studies
      showed that leptin had no effect on glucose transport, lipoprotein lipase
      activity, and insulin action in fat and muscle cells in vitro.

PMID- 9564864
TI  - Rat ovarian prostaglandin endoperoxide synthase-1 and -2: periovulatory
      expression of granulosa cell-based interleukin-1-dependent enzymes.
AB  - This laboratory has previously shown that interleukin-1 (IL-1), a putative
      intermediary in the ovulatory process, is capable of up-regulating PG
      biosynthesis by cultured whole ovarian dispersates from immature rats. In part,
      this phenomenon was attributable to the stimulation of ovarian phospholipase A2
      activity. In this communication we examine the possibility that the PG-promoting
      property of IL-1 is also due to the up-regulation of PG endoperoxide synthase
      (PGS), the rate-limiting step in prostanoid biosynthesis. The in vivo expression
      of ovarian PGS-2 transcripts in the course of a simulated estrous cycle rose
      abruptly to a peak (35-fold increase over the control value; P < 0.05) 8-12 h
      after hCG administration (i.e. before or during projected ovulation). PGS-1
      transcripts, in turn, were not significantly altered during the periovulatory
      period. Treatment of cultured whole ovarian dispersates with IL-1beta resulted in
      dose- and time-dependent up-regulation of PGS-2 transcripts (as well as of
      immunoreactive PGS-2 protein and PGE2 accumulation), characterized by an ED50 of
      2 ng/ml and a maximal (72-fold) increase at 10 ng/ml. Although treatment with IL
      1beta also led to an increase in PGS-1 transcripts and immunoreactive PGS-1
      protein, the relative magnitude of the effect was markedly reduced compared with
      that of PGS-2. Cotreatment with an IL-1 receptor antagonist completely reversed
      the IL-1 effects, thereby suggesting mediation via the IL-1 receptor. The ability
      of IL-1 to up-regulate PGS-2 transcripts proved relatively specific, in that
      other cellular regulators (insulin-like growth factor I, activin A, endothelin-1,
      transforming growth factor-alpha, tumor necrosis factor-alpha, vascular
      endothelial growth factor, leukemia inhibitor factor, hepatocyte growth factor,
      or keratinocyte growth factor) were not effective. The optimal IL-1 effect
      required heterologous contact-dependent coculturing of granulosa and thecal
      interstitial cells. Taken together, these observations 1) reaffirm (by molecular
      probing) the granulosa cell as the primary site of ovarian PGS-1 and PGS-2
      expression, 2) document an increase in ovarian PGS-2 transcripts before
      ovulation, and 3) reveal a marked dependence of ovarian PGS (2 >> 1) transcripts,
      proteins, and activity on IL-1. The effects of IL-1 proved relatively specific,
      contingent upon somatic cell-cell cooperation, dose and time dependent, and IL-1
      receptor mediated. These results are compatible with the proposition that the PG
      promoting property of IL-1 is due, in large measure, to the activation of ovarian
      PGS transcription and translation. The ability of IL-1 to up-regulate ovarian
      PGS, an obligatory component of ovulation, is in keeping with the idea that IL-1
      may constitute an intermediary in the ovulatory process.

PMID- 9564866
TI  - Vanadate elevates lipogenicity of starved rat adipose tissue: mechanism of
      action.
AB  - We have established an experimental system in rats in which the lipogenic
      capacity of adipose tissue was decreased in vivo by prolonged fasting, and
      restored in vitro by glucose together with insulin or vanadate. Incubation of
      fasted adipose explants for 5 h at 37 C with 2 mM glucose alone did not elevate
      lipogenic capacity. However, glucose with insulin (17 nM) or vanadate (100
      microM), led, respectively, to 2.2- and 8- to 10-fold elevation. Actinomycin D
      (50 microM) completely blocked this increase, while low concentrations (ED50 =
      4.0 +/- 0.4 microM) of vanadate potentiated it. Neither insulin nor vanadate
      elevated fasted adipose explants' lipogenic capacity in the absence of glucose,
      or in the presence of the nonmetabolizable glucose analog 3-O-methylglucose. Upon
      replacing glucose with 2-deoxyglucose (1 mM), a glucose analog that undergoes
      phosphorylation to 2-deoxyglucose-6-phosphate with no further metabolism,
      vanadate was nearly as potent as with glucose in elevating lipogenic capacity.
      Vanadate was superior to insulin in increasing glucose-6-phosphate level in
      fasted-adipose explants. Adipose glucose-6-phosphatase activity was inhibited by
      vanadate (IC50 = 7.0 +/- 0.4 microM). We have concluded that glucose-6-phosphate
      is the key metabolite of glucose involved in the transcriptionally regulated
      elevation of lipogenic capacity of fasted adipose explants. Vanadate has a more
      profound effect than insulin, as it elevates glucose-6-phosphate to higher levels
      and the subsequent increase in lipogenic capacity is four to five times greater
      than that induced by insulin. The mechanism involved is the combined action of
      vanadate in enhancing glucose entry and in inhibiting dephosphorylation of
      endogenously formed glucose-6-phosphate. The latter effect is not exerted by
      insulin.

PMID- 9564867
TI  - Mammogenic hormones differentially modulate keratinocyte growth factor (KGF)
      induced proliferation and KGF receptor expression in cultured mouse mammary gland
      epithelium.
AB  - Stromally derived keratinocyte growth factor (KGF) can play an important role in
      mammary gland development as a mesenchymal/stromal mediator of epithelial growth
      and morphogenesis. However, the possible coordinate regulation of mammary gland
      development by mammogenic hormones and KGF is unexplored. In these studies, the
      direct effect of mammogenic hormones on KGF-mediated mammary epithelial
      mitogenesis and expression of the KGF receptor was examined using primary mouse
      mammary epithelium growing in serum-free, collagen gel cell culture. Addition of
      KGF produced an average 7-fold increase in cell number after 10 days of culture.
      This effect of KGF was further increased in the presence of PRL (9-fold) or
      progesterone (P; 15-fold), with the combination of P and PRL (22-fold) producing
      the strongest synergistic stimulation. Estrogen did not show any additional
      stimulation of growth either alone or in combination with PRL and/or P.
      Ribonuclease protection analysis showed that epithelial cells grown in medium
      supplemented with P, but not PRL or estrogen, exhibited a 10-fold higher steady
      state level of KGF receptor (KGFR) messenger RNA (mRNA). KGFR expression was not
      induced by short term P exposure, suggesting an effect on mRNA stability rather
      than transcriptional activation. Time-course studies showed that an early
      decrease in the level of KGFR mRNA in basal cultures was significantly reduced by
      P addition. Measurement of RNA turnover after actinomycin D treatment showed that
      P increased the t(1/2) of KGFR mRNA compared with basal medium. Thus, P and PRL
      may differentially potentiate the direct mitogenic effect of KGF: P partly by
      elevation of the level of KGFR mRNA, and PRL principally by intracellular
      pathways not affecting KGFR expression.

PMID- 9564868
TI  - Thyroid hormone excess increases insulin-like growth factor I transcripts in bone
      marrow cell cultures: divergent effects on vertebral and femoral cell cultures.
AB  - Thyroid hormones (T3 and T4) regulate bone development, growth, and turnover.
      Studies have suggested that different skeletal sites respond differently to
      thyroid hormones. Therefore, we examined the in vitro T3 responsiveness of cells
      committed to the osteoblast lineage as a function of skeletal location. Bone
      marrow cells derived from female rat femurs and vertebrae were cultured using
      conditions that induce osteogenic differentiation. Cells from both sites formed
      mineralized bone nodules in primary and secondary culture. In femoral cultures,
      collagen type I (coll I) and osteocalcin (OC) messenger RNA (mRNA) levels
      increased from the earliest time point examined (day 3) to a maximum on day 12
      and thereafter declined to undetectable levels. T3 increased both OC and coll I
      mRNA, resulting in a continuous expression throughout the culture period. Insulin
      like growth factor I (IGF-I) gene expression was detected at very low levels by
      Northern analysis of femoral total RNA, and T3 only marginally enhanced IGF-I
      mRNA levels. In vertebral cultures, OC and coll I mRNA levels also increased with
      time in culture, but remained expressed throughout the culture period. OC and
      coll I mRNA levels were not markedly altered in response to T3. In contrast to
      femoral cells, IGF-I gene expression was easily visualized in Northern blots from
      untreated vertebral cultures and was markedly increased by the addition of T3.
      The continuous presence of T3 (10(-7) M) in the medium for 18 days caused a
      marked decrease in the number of alkaline phosphatase-positive colonies formed in
      femoral secondary cultures, but only a slight decrease in the number in vertebral
      cultures. In addition, short term (6 days) exposure to T3 (10(-7) M) at the
      beginning of the culture period decreased alkaline phosphatase activity in
      femoral cultures, but not in vertebral cultures. These findings indicate that
      there are skeletal site-dependent differences in the in vitro responses of cells
      of the osteoblastic lineage to thyroid hormone.

PMID- 9564869
TI  - The thyroid hormone receptor variant alpha2 is a weak antagonist because it is
      deficient in interactions with nuclear receptor corepressors.
AB  - The thyroid hormone receptor splice variant, alpha2, is unable to bind thyroid
      hormone (T3) and has been proposed to function as an endogenous inhibitor of T3
      action. In this report, we examined further the DNA sequence requirements for
      alpha2 binding to thyroid hormone response elements (TREs) in an attempt to
      identify response elements that mediate potent inhibition by alpha2. Heterodimers
      of alpha2 and retinoid X receptor were found to bind to a subset of TREs (DR4,
      direct repeats spaced by 4 bp) in which selected flanking and spacer sequences
      enhanced interactions with the AGGTCA core binding sequence. Despite the
      optimization of the TRE-binding sites, alpha2 remained a weak dominant negative
      inhibitor of TRE-driven transcription. A promoter interference assay was also
      developed for testing inhibition by alpha2. In these studies, alpha2 blocked gene
      transcription, but it required cotransfected retinoid X receptor, and it was not
      as potent as unliganded thyroid hormone receptors. These results led to the
      hypothesis that alpha2 might be deficient in interactions with nuclear receptor
      corepressors. Consistent with this view, alpha2 did not silence basal
      transcription in its native form or when linked to Gal4. Alpha2 also failed to
      interact with corepressors (NCoR and SMRT) in both gel shift assays and mammalian
      two-hybrid assays. We conclude that alpha2 is a weak antagonist of thyroid
      hormone action because it binds weakly to a limited repertoire of response
      elements, and it does not interact with corepressors. Thus, alpha2 may be able to
      compete with thyroid hormone receptors for binding to a limited group of target
      sites, but it is not able to actively inhibit transcription.

PMID- 9564870
TI  - The growth hormone (GH) gene is expressed in the lateral hypothalamus:
      enhancement by GH-releasing hormone and repression by restraint stress.
AB  - Recent studies suggest that GH may modulate emotion, behavior, or stress response
      by its direct actions on the brain, and possible expression of the GH gene in the
      brain has been predicted. In this study we have investigated whether and where
      the GH gene is expressed in the brain and how it is regulated. Ribonuclease
      protection assay and 5'-rapid amplification of complementary DNA ends-PCR
      analyses indicated that the GH gene was expressed in rat brain, initiating at the
      identical transcription start point as that for pituitary GH gene expression. The
      brain GH messenger RNA was predominantly detected in the lateral hypothalamus
      (lh) by in situ reverse transcription-PCR analysis. GH gene expression in the
      brain was significantly enhanced by GH-releasing hormone administration and was
      rapidly repressed by exposure to restraint stress in the water, whereas the
      changes in pituitary GH messenger RNA contents in these circumstances were
      relatively smaller. The results of the present study suggest that the brain GH is
      predominantly expressed in lh under the control of physiological conditions to
      play a role in the modulation of brain functions.

PMID- 9564871
TI  - Adrenomedullin production in fibroblasts: its possible function as a growth
      regulator of Swiss 3T3 cells.
AB  - In addition to endothelial cells and vascular smooth muscle cells, we
      demonstrated that adrenomedullin (AM) is synthesized and secreted from
      fibroblasts, Swiss 3T3, Hs68, and NHLF cells, in a native and biologically active
      form. Synthesis and secretion of AM from these fibroblasts was regulated by
      inflammatory cytokines, such as tumor necrosis factor and interleukin-1,
      lipopolysaccharide, growth and differentiation factors, and hormones in a manner
      similar to that of vascular smooth muscle cells and endothelial cells. Tumor
      necrosis factor-alpha, interleukin-1beta, and dexamethasone elevated AM
      secretion, whereas transforming growth factor-beta1 and interferon-gamma
      suppressed it in these three fibroblasts. Swiss 3T3 cells were shown to express
      receptors specific for AM by both cAMP production and receptor binding assay, and
      AM was found to stimulate DNA synthesis of quiescent cells through the cAMP
      mediated pathway. AM secreted from Swiss 3T3 cells was also confirmed to augment
      cAMP production and DNA synthesis in the cells themselves. These effects were
      inhibited by a neutralizing monoclonal antibody against AM. These findings raise
      the possibility that AM functions as a growth regulator in the case of Swiss 3T3
      cells. As AM receptors are widely distributed, AM secreted from fibroblast may
      play a role as a local regulator in mesenchymal cells of inflammatory or wounded
      regions.

PMID- 9564872
TI  - Chemoreflex contribution to adrenocortical function during acute hypoxemia in the
      llama fetus at 0.6 to 0.7 of gestation.
AB  - This study tested the hypothesis that the fetal llama, a species adapted to the
      chronic hypoxia of life at high altitude, demonstrates a potent carotid
      chemoreflex influence on adrenocortical responses during acute hypoxemia. Plasma
      ACTH and cortisol concentrations, and mesencephalic and adrenal blood flows were
      measured during a 1-h period of acute hypoxemia in six intact and four carotid
      sinus-denervated llama fetuses at 0.6-0.7 of gestation. Fetal PaO2 was reduced
      from approximately 23 to about 14 mm Hg in both intact and carotid-denervated
      groups during acute hypoxemia. During hypoxemia, fetal plasma ACTH, adrenal blood
      flow, and, therefore, delivery of ACTH to the adrenals increased to similar
      extents in both intact and carotid-denervated fetal llamas. Despite this, the
      increase in plasma cortisol in hypoxemia in intact fetuses was absent in carotid
      denervated fetuses. In addition, the increase in delivery of cortisol to the
      mesencephalon calculated in intact fetuses during hypoxemia did not occur in the
      carotid-denervated group. These data suggest that the integrity of the carotid
      chemoreceptors is indispensable to cortisol release during acute hypoxemia in the
      llama fetus, even at 0.6-0.7 of gestation.

PMID- 9564873
TI  - Expression of growth differentiation factor-9 messenger ribonucleic acid in
      ovarian and nonovarian rodent and human tissues.
AB  - Growth differentiation factor-9 (GDF-9) is a member of the transforming growth
      factor-beta family that is reported to be expressed exclusively in the ovary,
      specifically in the oocyte. Female mice deficient in GDF-9 are infertile,
      suggesting that GDF-9 receptor agonists and antagonists may specifically modulate
      fertility. We now report that GDF-9 messenger RNA (mRNA) is expressed in
      nonovarian tissues in mice, rats, and humans. GDF-9 mRNA was detected in mouse
      and rat ovary, testis, and hypothalamus by Northern blot and RT-PCR analyses. The
      localization of GDF-9 mRNA specifically in oocytes of the mouse ovary was
      confirmed by in situ hybridization histochemistry. In mouse testis, although
      localization in Sertoli cell cytoplasm could not be ruled out, mRNA expression
      was observed in large pachytene spermatocytes and round spermatids. The
      expression of GDF-9 mRNA in human tissues was assessed by Northern blot and RT
      PCR analyses. GDF-9 mRNA was observed in ovary and testis and, surprisingly, in
      diverse nongonadal tissues, including pituitary, uterus, and bone marrow.
      Therefore, GDF-9 mRNA expression in rodents is not exclusive to the ovary, but
      includes the testis and hypothalamus. Furthermore, human GDF-9 mRNA is expressed
      not only in the gonads, but also in several extragonadal tissues. The function
      and relevance of nongonadal GDF-9 mRNA are not known, but may affect strategies
      for contraception and fertility that are based on GDF-9 activity.

PMID- 9564874
TI  - Cardiac senescence is associated with enhanced expression of angiotensin II
      receptor subtypes.
AB  - Recent studies have pointed out the differential role of angiotensin II (Ang II)
      receptor subtypes, AT1 and AT2, in cardiac hypertrophy and fibrosis during
      pathological cardiac growth. Because senescence is characterized by an important
      cardiovascular remodeling, we examined the age-related expression of cardiac Ang
      II receptors in rats. AT1 and AT2 receptor subtype messenger RNA (mRNA) levels
      were quantitated by RT-PCR. In parallel, specific Ang II densities were
      determined in competition binding experiments using specific antagonists. AT1a
      and AT1b mRNA levels were markedly up-regulated (5.6-fold) in the left ventricle
      of 24-month-old rats compared with 3-month-old rats, but not in the right
      ventricle. In contrast, AT2 gene expression was increased in both ventricles of
      senescent rats (4.2- and 2.8-fold in the left and right ventricles,
      respectively). Similarly, AT1 and AT2 gene expression was increased 2.3- and 2
      fold, respectively, in freshly isolated cardiomyocytes from aged rats.
      Furthermore, AT1 and AT2 specific binding was increased in the aged left
      ventricular myocardium. Even though the mechanistic pathway of this up-regulation
      of Ang II receptor subtype gene expression might be intrinsic to developmental
      gene reprogramming, the up-regulation of AT1 mRNA accumulation in the left
      ventricle during aging could also be secondary to age-related hemodynamic
      changes, whereas increased AT2 gene expression in both ventricles may depend upon
      hormonal and humoral factors.

PMID- 9564875
TI  - The olfactory adenylyl cyclase III is expressed in rat germ cells during
      spermiogenesis.
AB  - To identify the adenylyl cyclase (AC) genes expressed in mammalian germ cells, RT
      PCR of testis and germ cell RNA was performed using degenerated primers based on
      the homologous region of the AC catalytic domain. This strategy yielded high
      frequency amplification of a complementary DNA (cDNA) identical to type III AC
      (ACIII), a form previously identified as the major adenylyl cyclase expressed in
      the olfactory system. Ribonuclease protection studies confirmed that ACIII
      transcripts are present in germ cells, appear during the meiotic prophase, and
      accumulate during spermiogenesis. A Northern blot analysis performed on total
      testis RNA demonstrated the presence of a predominant transcript of 7.5 kb,
      suggesting that the ACIII expressed in germ cells may derive from a splicing
      variant different from the 4.5 kb transcripts expressed in somatic cells. To
      determine whether these RNAs are translated into a protein, Western blot analysis
      was performed using an antibody specific for the carboxyl terminus of ACIII. An
      immunoreactive protein of 170 kDa was detected in extracts from total testis and
      from germ cells. Immunofluorescence localization of this protein in the
      seminiferous tubules showed that ACIII was predominantly expressed in postmeiotic
      germ cells from round spermatids in the cap phase to maturing elongating
      spermatids. The ACIII antigen was located mostly on the acrosomal membrane rather
      than on the plasma membrane of developing spermatids. The spatial and temporal
      expression of ACIII in germ cells indicates a role of this AC in the acrosome
      formation. Together with the observation that members of the olfactory receptor
      family and an olfactory phosphodiesterase are expressed in spermatids, these
      findings suggest that a signal transduction system used in olfaction is also used
      during gamete development.

PMID- 9564876
TI  - Expression of estrogen receptor-beta messenger ribonucleic acid in oxytocin and
      vasopressin neurons of the rat supraoptic and paraventricular nuclei.
AB  - The regulatory actions of estrogen on magnocellular oxytocin (OT) and vasopressin
      (VP) neurons of the paraventricular (PVN) and supraoptic (SON) nuclei are well
      documented. To date it is still debated whether the effect of estrogens is
      exerted directly or mediated by estrogen-sensitive interneurons. Previous
      immunocytochemical (ICC) and in situ hybridization (ISH) studies detected either
      low levels or absence of the classical estrogen receptor (ER-alpha) in the PVN
      and the SON of the rat. The present experiments using a combined ICC and ISH
      method were undertaken to examine the expression of the recently cloned beta form
      of ER (ER-beta) in OT- and VP-immunoreactive (IR) neuronal systems of the rat
      hypothalamus. The results demonstrate that the highest cellular levels of ER-beta
      messenger RNA (mRNA) in OT-IR neurons can be visualized in the caudal portion of
      the PVN and in an area ventro-medial to the central core of VP-IR cells. These
      neurons were previously shown to project caudally to the brain stem and the
      spinal cord to regulate autonomic functions. In addition, the whole rostro-caudal
      extent of the PVN and the SON contained OT-IR neurons that coexpressed variable
      levels of ER-beta mRNA. Similarly, the presence of ER-beta mRNA was seen in a
      large population of VP-IR paraventricular and supraoptic neurons. In the SON,
      somewhat stronger hybridization signal was detected in VP-IR neurons as compared
      with OT-IR neurons. Together, these findings provide strong support for the
      concept that the functions of OT- and VP-IR neurons in the PVN and the SON are
      regulated directly by estrogen and that the genomic effects of estrogens are
      mediated by ER-beta.

PMID- 9564877
TI  - Overexpression of insulin-like growth factor-binding protein-4 (IGFBP-4) in
      smooth muscle cells of transgenic mice through a smooth muscle alpha-actin-IGFBP
      4 fusion gene induces smooth muscle hypoplasia.
AB  - Insulin-like growth factor I (IGF-I) has been postulated to function as a smooth
      muscle cell (SMC) mitogen and to play a role in the pathogenesis of bladder
      hypertrophy, estrogen-induced uterine growth, and restenosis after arterial
      angioplasty. IGF-binding protein-4 (IGFBP-4) inhibits IGF-I action in vitro and
      is the most abundant IGFBP in the rodent arterial wall. To explore the function
      of this binding protein in vivo, transgenic mouse lines were developed harboring
      fusion genes consisting of a rat IGFBP-4 complementary DNA cloned downstream of
      either a -724 bp fragment of the mouse smooth muscle alpha-actin 5'-flanking
      region (SMP2-BP-4) or -1074 bp, 63 bp of 5'-untranslated region, and 2.5 kb of
      intron 1 of smooth muscle alpha-actin (SMP8-BP-4). SMP2-BP-4 mice expressed low
      levels of the exogenous IGFBP-4 messenger RNA (mRNA), which was not specifically
      targeted to SMC-rich tissue environments, and were therefore not analyzed
      further. Six SMP8-BP-4 transgenic lines derived from separate founders were
      characterized. Mating of hemizygous SMP8-BP-4 mice with controls produced about
      50% transgenic offspring, with equal sex distribution. Expression of IGFBP-4 mRNA
      in nontransgenic littermates was maximal in liver and kidney. By contrast,
      transgenic IGFBP-4 mRNA expression, distinguished because of a smaller transcript
      size, was confined to SMC-containing tissues, with the following hierarchy:
      bladder > aorta > stomach = uterus. There was no transgene expression in skeletal
      muscle, brain, or cardiac myocytes. The abundance of IGFBP-4 measured by Western
      ligand blotting or by immunoblotting, was 8- to 10-fold higher in aorta and
      bladder of SMP8-BP-4 mice than in their nontransgenic littermates, with no change
      in plasma IGFBP-4 levels. Transgenic mice exhibited a significant reduction in
      wet weight of SMC-rich tissues, including bladder, intestine, aorta, uterus, and
      stomach, with no change in total body or carcass weight. In situ hybridization
      showed that transgene expression was targeted exclusively to the muscular layers
      of the arteries, veins, bladder, ureter, stomach, intestine, and uterus.
      Overexpression of IGFBP-4 was associated with SMC hypoplasia, a reciprocal
      phenotype to that of transgenic mice overexpressing IGF-I under control of the
      same promoter (SMP8-IGF-I). Double transgenic mice derived from mating SMP8-BP-4
      with SMP8-IGF-I animals showed a modest decrease in wet weight at selected SMC
      tissues. Although we cannot exclude that the effects of IGFBP-4 may be IGF
      independent, these data suggest that IGFBP-4 is a functional antagonist of IGF-I
      action on SMC in vivo.

PMID- 9564878
TI  - Functional receptors for atrial natriuretic peptide in the rat mammary gland
      during lactation.
AB  - The present study was undertaken: 1) to localize and characterize atrial
      natriuretic peptide (ANP) receptors in the rat mammary gland; and 2) to elucidate
      ANP-induced cellular formation of cyclic GMP (cGMP) and alterations in alveolar
      morphology during both early and late lactation. Receptor autoradiography,
      employing rat-specific [125I]ANP as radioligand, demonstrated binding sites in
      the secretory tissue and larger blood vessels of the mammary gland. Binding of
      [125I]rANP to membrane fractions was completely displaced by unlabeled ANP and
      brain natriuretic peptide. C-type natriuretic peptide and cANP(4-23) revealed
      limited competition with radiolabeled ANP only during early lactation, indicating
      a more heterogeneous receptor population at that time. Systemically administered
      ANP induced cGMP formation in the alveolar epithelium, as shown with
      immunohistochemistry, and increased mammary tissue cGMP concentrations in vivo
      throughout the lactation period. Image analysis revealed enlargement of alveolar
      (but not epithelial) cell area after ANP stimulation in late lactation,
      suggesting altered alveolar filling or myoepithelial cell relaxation. These
      results indicate that ANP induces biological effects in the rat mammary gland
      through specific ANP-A receptor interaction with subsequent intracellular cGMP
      formation. ANP may therefore play a regulatory role in the control of mammary
      gland blood supply and secretory function.

PMID- 9564879
TI  - 1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression
      in murine bone marrow stromal cell clones and primary cultures.
AB  - Bone marrow stromal stem cells differentiate into adipocytes and osteoblasts.
      These two lineages are thought to be reciprocally related, in part due to the
      observation that the osteoblast-inducing factor, 1,25 dihydroxy vitamin D3
      [1,25(OH)2D3], inhibited adipogenesis of rat femoral-derived stromal cell
      cultures. However, the literature is divided concerning the adipogenic effects of
      this steroid hormone. This work examined the effect of 1,25(OH)2D3 (10(-12)-10(
      8) M) on murine femoral-derived bone marrow stromal cell differentiation in
      response to adipogenic agonists employing two different classes of nuclear
      hormone receptors: the glucocorticoid receptor (hydrocortisone) or peroxisome
      proliferator-activated receptors (thiazolidinediones). Experiments used the
      multipotent murine bone marrow stromal cell line, BMS2, and its subclones, as
      well as primary-derived murine bone marrow stromal cell cultures. In all systems
      examined, 1,25(OH)2D3 blocked adipogenesis induced by hydrocortisone,
      methylisobutylxanthine, and indomethacin based on flow cytometric analysis of
      lipid accumulation. This correlated with reduced messenger RNA levels of the late
      adipocyte gene markers, aP2 and adipsin. In the BMS2 subclone no. 24, the
      1,25(OH)2D3 actions were concentration dependent. Whereas 1,25(OH)2D3 partially
      inhibited thiazolidinedione-induced adipogenesis in the parental BMS2 cell line,
      it had minimal effect on the thiazolidinedione-induced differentiation of the
      BMS2 subclone and primary cultures. These findings indicate that 1,25(OH)2D3, at
      nanomolar concentrations, completely inhibits murine bone marrow stromal cell
      differentiation in response to glucocorticoid-based adipogenic agonists but is a
      less effective adipogenic antagonist following induction with thiazolidinediones.
      This work supports the conclusion that 1,25(OH)2D3 inhibits murine femoral
      derived bone marrow stromal cell adipogenesis.

PMID- 9564880
TI  - Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene
      transcription in vivo revealed by expression of a lacZ reporter gene.
AB  - Neuropeptide Y (NPY), a peptide synthesized in the hypothalamic arcuate nucleus,
      is implicated in the physiologic control of food intake and body weight. Because
      both genetic (e.g. in obese ob/ob mice) and acquired leptin deficiency (e.g.
      fasting in normal mice) increase hypothalamic NPY accumulation, and as leptin
      administration reverses this effect, we hypothesized that leptin inhibits
      transcription of the NPY gene by arcuate nucleus neurons. To test this
      hypothesis, we studied mice with a targeted mutation of the NPY gene (NPY
      knockout mice), in which the lacZ reporter gene was inserted into the first exon
      of the NPY gene. As a result, these mice express beta-galactosidase (beta gal;
      the enzyme encoded by lacZ) in neurons that normally express the NPY gene. To
      determine whether beta gal staining provides a valid measure of lacZ expression,
      we used a histochemical method to count the number of beta gal+ neurons in
      coronal sections of brain tissue from mice bearing either one (NPY+/-) or two
      (NPY-/-) mutant alleles. In both the arcuate nucleus and the thalamic reticular
      nucleus, beta gal+ cell number was 260% higher in NPY-/- than in NPY+/- mice (P <
      0.05). Fasting for 48 h also increased the mean beta gal+ cell number in the
      arcuate nucleus of NPY+/- mice by 260% (P < 0.001), but had no effect in the
      thalamic reticular nucleus. Similarly, obese leptin-deficient ob/ob, NPY+/- mice
      had a 67.3% increase in arcuate nucleus beta gal+ cell number compared with lean
      ob/+, NPY+/- littermates (P < 0.05), and this effect was attenuated 36.6% (P <
      0.05) by leptin administration (70 microg/day, i.p., for 4 days). Based on the
      results of this novel method for measuring NPY gene transcription in vivo, we
      conclude that both fasting and genetic leptin deficiency increase NPY gene
      transcription in the arcuate nucleus and that this transcriptional response is
      attenuated by leptin administration in ob/ob, NPY+/- mice.

PMID- 9564881
TI  - Identification and regulation of testicular interferon-gamma (IFNgamma) receptor
      subunits: IFNgamma enhances interferon regulatory factor-1 and interleukin-1beta
      converting enzyme expression.
AB  - Interferon-gamma (IFNgamma) transmits its signal through a specific cell surface
      receptor (IFNgammaR), which consists of a primary ligand binding alpha-chain
      (IFNgammaR alpha) and a signaling beta-chain (IFNgammaR beta). Recent studies
      identified the cytokines IFNgamma, interleukin-6 (IL-6), IL-1alpha, and tumor
      necrosis factor-alpha in testicular cells. Therefore, we: 1) examined the
      expression of IFNgammaR alpha and IFNgammaR beta subunits in freshly isolated and
      purified rat testicular cells; 2) examined the differential regulation of
      receptor components by cytokines using primary cultures of Sertoli cells; 3)
      identified the cell signaling pathway components of testicular IFNgammaR; and 4)
      characterized the functional role of testicular IFNgamma using primary Sertoli
      cells. We demonstrated the messenger RNAs for both chains of IFNgammaR in rat
      testicular cells using Northern hybridization analysis. Western blot analysis and
      immunocytochemistry showed that both specific IFNgammaR protein subunits were
      present in cultured primary Leydig and Sertoli cells prepared from the testes of
      immature rats. The expression of both IFNgammaR component messenger RNAs in
      cultured Sertoli cells was increased by its specific ligand (IFNgamma), as well
      as IL-1alpha and tumor necrosis factor-alpha, in both a time- and dose-dependent
      manner. IFNgamma-activation of the Janus (JAK) tyrosine kinases, JAK1 and JAK2
      proteins, indicate that IFNgammaR, expressed in the Sertoli cell, is functional.
      Moreover, IFNgamma modulates the expression of interferon regulatory factor (IRF)
      1 and IL-1beta converting enzyme genes in Sertoli cells. Thus, our data are
      suggestive of a role(s) for IFN-gamma in the regulation of distinct gene
      expression and cell-specific sensitivity to apoptosis in the testis.

PMID- 9564882
TI  - Effect of twenty-four-week treatment with the antiestrogen EM-800 on estrogen
      sensitive parameters in intact and ovariectomized mice.
AB  - Treatment with the antiestrogen EM-800, at the daily oral dose of 3 microg, 10
      microg, 30 microg, or 100 microg for 24 weeks, caused a marked inhibition of
      uterine and vaginal weight in both intact and ovariectomized mice. Maximal 64%
      and 41% inhibitions of uterine weight were achieved in intact and ovariectomized
      animals, respectively. Similar inhibitory effects of EM-800 were observed on
      vaginal weight with maximal inhibitions of 71% and 35%, in intact and
      ovariectomized animals, respectively. The pure antiestrogenic activity of EM-800
      on the hypothalamo-pituitary-ovarian axis is illustrated by the 76-91% increases
      in ovarian weight observed in intact animals treated with the 10-100 microg doses
      of the antiestrogen. Serum 17beta-estradiol was 93% increased at the 100 microg
      daily dose of EM-800, whereas serum androstenedione, testosterone, and
      dihydrotestosterone were 141-713% increased over control at the same dose of the
      antiestrogen. Serum LH was increased by treatment with EM-800 in intact animals,
      whereas no effect was observed on the elevated gonadotropin levels in
      ovariectomized animals. At all doses used in intact animals, the antiestrogen
      caused a complete disappearance of the glandular elements of the mammary gland,
      the atrophy being comparable with that observed in ovariectomized mice. The
      mammary gland of EM-800-treated animals was exclusively composed of an atrophied
      ductal system lined by atrophied epithelial cells with an absence of lobulo
      glandular elements. No effect of the compound was observed on the histology of
      the mammary gland in ovariectomized animals, thus showing the pure antiestrogenic
      effect of EM-800 on the mammary gland, as shown also for the uterus, vagina, and
      hypothalamo-pituitary axis. At histopathology, all doses of EM-800 in intact
      animals led to a moderate to severe uterine and vaginal atrophy. The uterine
      atrophy affected both the myometrium and the endometrium. Interestingly, the
      uterine atrophy achieved in intact animals treated with EM-800 was greater than
      that observed after ovariectomy alone, thus clearly demonstrating the pure
      antiestrogenic activity of EM-800. The present data show the highly potent and
      pure antiestrogenic activity of EM-800 on all parameters measured after 6 months
      of treatment in both intact and ovariectomized mice, a maximal effect being
      reached at the daily 10 microg dose of the antiestrogen in intact animals.

PMID- 9564883
TI  - Signaling by leukocyte chemoattractant and Fcgamma receptors in immune-complex
      tissue injury.

PMID- 9564884
TI  - Cell-specific gene expression reveals changes in epithelial cell populations
      after bleomycin treatment.
AB  - Epithelial repair following acute lung injury involves proliferation and
      differentiation of existing Clara cells and type II cells. Other mechanisms of
      epithelial repair may be involved in particularly severe cases. We used
      epithelial cell-specific markers to examine changes in the mouse lung epithelium
      28 days after bleomycin treatment. The spatial distribution of surfactant
      proteins A, B, C (SPA, SPB, SPC), and Clara cell-specific protein (CC10) mRNA was
      compared by in situ hybridization in serial lung sections. CC10 mRNA-containing
      airway cells were replaced in many areas by SPB mRNA-expressing, ciliated cells
      that did not contain CC10 mRNA. In distal airway regions, we observed a
      subpopulation of epithelial cells that appeared to express SPA, SPB, SPC, and
      CC10 mRNA, and speculated that they may represent a multipotential stem cell
      population. These cells were found in focal clusters, which suggests that they
      expanded from a common cell. CC10 mRNA-containing cells were seen in alveolar
      like structures thought to be the result of Clara cell migration or outpocketing.
      Our data suggest that there are repair mechanisms involved in epithelial repair
      after severe injury that have not previously been described.

PMID- 9564885
TI  - P53- and CD95-associated apoptosis in neurodegenerative diseases.
AB  - Apoptosis is likely to be an important mechanism of cell loss in
      neurodegenerative diseases, but the signaling cascades activated before DNA
      fragmentation have not yet been determined. p53 or CD95 gene up-regulation
      precedes apoptosis in many cell types, and a potential role for these molecules
      in apoptosis of neurons and glial cells has already been demonstrated in
      Alzheimer's disease (AD). To determine whether apoptosis in other
      neurodegenerative diseases is mediated by similar mechanisms, p53 and CD95
      expression were examined in postmortem central nervous system tissues from
      patients with diffuse Lewy body disease (DLBD), Pick's disease (PkD), progressive
      supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson's disease
      (PD), amyotrophic lateral sclerosis (ALS), and Down's syndrome plus Alzheimer's
      disease (DN+AD). Quantitative immunoblot analysis demonstrated higher temporal
      lobe levels of p53 and CD95 proteins in DLBD, PkD, and DN+AD, and higher temporal
      lobe levels of CD95 only in MSA and PSP relative to PD and aged controls (for
      all, p < 0.01). In histologic sections, increased p53 immunoreactivity was
      localized in neuronal and glial cell nuclei, neuronal perikarya, and dystrophic
      neuritic and glial cell processes in the frontal (Area 1 1) and temporal (Area
      21) lobes in DLBD, PkD, and DN+AD, the motor cortex and spinal ventral horns in
      ALS, and the striatum and midbrain in DLBD, MSA, PD, and PSP. Increased CD95
      expression and nuclear DNA fragmentation were present in the same cell types and
      structures that manifested increased nuclear p53 immunoreactivity. The results
      suggest that p53- or CD95-associated apoptosis may be a common mechanism of cell
      loss in several important neurodegenerative diseases. In addition, the presence
      of abundant p53-immunoreactive neurites and glial cell processes appears to be a
      novel feature of neurodegeneration shared by these distinct diseases.

PMID- 9564886
TI  - Protein kinase Calpha controls the adhesion but not the antiproliferative
      response of human colon carcinoma cells to transforming growth factor beta1:
      identification of two distinct branches of post-protein kinase Calpha adhesion
      signal pathway.
AB  - Transforming growth factor beta1 (TGFbeta1) inhibits cellular proliferation and
      induces the expression of the matrix adhesion molecules fibronectin (FN) and
      laminin (LM) in a concurrent manner, followed by the induction of the
      intercellular adhesion molecule carcinoembryonic antigen (CEA) (collectively
      designated as adhesion responses) in TGFbeta1-responsive human colon carcinoma
      cells. Exactly how TGFbeta1 controls cellular adhesion and proliferation is
      poorly understood. In the present report, we showed that down-regulating protein
      kinase Calpha (PKCalpha) expression blocked the induction of these adhesion
      responses by TGFbeta1, showing that PKCalpha is a postreceptor focal point
      controlling the induction of these molecules. Down-regulating PKCalpha
      expression, however, had minimal effect on the antiproliferative response to
      TGFbeta1 or the induction of p21/WAF1, a marker associated with the
      antiproliferative effect of TGFbeta1, demonstrating that the adhesion signal
      pathway is distinct from that of antiproliferation. Blockade of FN induction
      blocked the induction of CEA but not the induction of LM. Blockade of LM
      induction, on the other hand, had no effect on the induction of FN and CEA. These
      results established the existence of two distinct and parallel postPKCalpha
      adhesion signal pathways, one leading to the induction of LM and the other
      leading to the induction of FN and CEA.

PMID- 9564887
TI  - Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice.
AB  - To clarify the role of type I and type II macrophage scavenger receptors (MSR-A)
      in the progression of diet-induced atherosclerosis, we generated mice lacking
      both MSR-A and low-density lipoprotein receptor (LDLR). After 4 or 12 weeks of a
      high-fat diet, the sizes of atherosclerotic lesions in MSR-A/LDLR double knockout
      mice were significantly reduced (p < 0.05) compared with those in LDLR single
      knockout mice. However, atherosclerotic lesions mainly composed of foamy
      macrophages were still observed in double knockout mice. Formation of
      atherosclerotic lesions in double knockout mice was partially explained by the
      participation of scavenger receptors other than MSR-A such as MARCO, CD36, and
      macrosialin/CD68. These receptors were clearly demonstrated in the
      atherosclerotic lesions in double knockout mice as well as LDLR single knockout
      mice by immunohistochemistry or by reverse transcriptase-polymerase chain
      reaction. Because the very low density lipoprotein (VLDL) fraction was elevated
      in the double and single knockout mice, we further examined the possibility that
      VLDL may participate in foam cell formation in atherosclerotic lesions. When
      incubated with VLDL isolated from LDLR-deficient mice, cholesterol ester
      accumulation and foamy transformation occurred in MSR-A-deficient macrophages as
      well as in normal macrophages. These data indicate that MSR-A plays an essential
      role in the development of diet-induced atherosclerosis. It also appears that
      other scavenger receptors, such as MARCO, CD36, and macrosialin/CD68, as well as
      uptake of VLDL are involved in foam cell formation during atherogenesis in MSR
      A/LDLR double knockout mice.

PMID- 9564888
TI  - Immunophenotypic characterization of simian immunodeficiency virus-infected
      dendritic cells in cervix, vagina, and draining lymph nodes of rhesus monkeys.
AB  - Significant progress has been made in understanding the biology of heterosexual
      transmission of HIV by utilizing the simian immunodeficiency virus (SIV)/rhesus
      monkey animal model. Our previous studies have shown that SIV-infected cells
      within the stratified squamous epithelium of the vagina have a dendritic
      morphology. However, the type of cell infected was not conclusively determined.
      The purpose of the present study was to immunophenotype the SIV-infected cells in
      the lower reproductive tract and genital lymph nodes of the female rhesus monkey.
      Vagina, cervix, and iliac lymph node from eight chronically SIV-infected adult
      female monkeys were examined for this study. None of the animals had histologic
      evidence of opportunistic infections or genital tract pathogens other than SIV.
      Combined in situ hybridization and immunohistochemistry were used to detect SIV
      RNA and to determine the immunophenotype of SIV-infected cells in tissue sections
      and cytospin preparations of cells from the tissues. We now show that SIV
      infected cells were most common in iliac lymph node and that the majority of
      infected cells in the lymph node were T lymphocytes. SIV-infected macrophages,
      Langerhans' cells, and dendritic cells were also found in the lymph node. SIV
      infected cells were found within the epithelium and lamina propria of the vagina.
      Although most of the infected cells were T cells, a significant proportion
      (approximately 40%) of the SIV-infected cells in cytospin preparations from
      explant cultures of vagina and cervix were Langerhans' cells. SIV-infected T
      cells in the lower genital tract were commonly associated with focal mononuclear
      cell infiltrates. SIV-infected macrophages were rarely found in the genital
      tract. The present study provides the first direct demonstration that Langerhans'
      cells and dendritic cells in the genital tract and lymph nodes are infected with
      SIV in vivo. Thus, dendritic cells, in general, and Langerhans' cells, in
      particular, are important reservoirs for HIV/SIV replication in vivo.

PMID- 9564889
TI  - Detection of soluble Fas mRNA using in situ reverse transcription-polymerase
      chain reaction.
AB  - Fas protein (Fas) is known to induce cell death by apoptosis in susceptible
      cells. Alternative splicing of the Fas gene produces soluble Fas protein (sFas),
      which is considered to block the function of Fas. The serum level of sFas is
      elevated in patients with various malignancies in a manner reflective of disease
      stage and tumor burden, but the precise cellular origin of sFas in vivo has not
      yet been clarified. To identify the cells that synthesize sFas mRNA on histologic
      specimens, we applied in situ reverse transcription-polymerase chain reaction (in
      situ RT-PCR) in 11 cases of gastric adenocarcinoma/metastatic lymph node.
      Furthermore, we studied the distribution of Fas using immunohistochemistry and
      Fas mRNA using in situ RT-PCR. In all primary tumors and 10 of 11 metastatic
      tumors, tumor cells expressed both Fas- and sFas mRNA. Lymphocytes infiltrated in
      the tumor tissues and the lymph nodes also revealed both mRNA signals. A clear
      correlation between the tissue distribution for Fas and its mRNA was also
      observed. These observations demonstrated that solid tumors in vivo can
      synthesize sFas mRNA and suggest that tumor cells are responsible in part for
      elevated sFas in human malignancies. However, the additional expression of sFas
      mRNA in tissue lymphocytes indicates the complex regulatory mechanisms of Fas
      mediated apoptosis pathway in tumor pathogenesis and host defense. We also
      demonstrated that in situ RT-PCR can be a suitable method for in situ detection
      of alternatively spliced mRNA.

PMID- 9564890
TI  - Secretion of Alzheimer's disease Abeta amyloid peptide by activated human
      platelets.
AB  - Alzheimer's disease (AD) is characterized by the deposition of Abeta (betaA4)
      peptides of 39 to 43 amino acid residues, which are normal cellular metabolic
      products derived by proteolysis of the amyloid precursor protein (APP). The
      physiologic function of Abeta/APP in vivo is poorly understood. We analyzed human
      platelets for Abeta production by immunoprecipitation coupled to immunoblotting.
      A 4-kd Abeta fragment that comigrates with an Abeta40 synthetic peptide and
      reacts with several antibodies specific for the N- and C-termini of Abeta is
      detected. The majority of platelet Abeta appears to end at residue 40, as
      determined by immunoreactivity with an Abeta40-specific antibody. Furthermore,
      Abeta is secreted upon platelet stimulation with the physiologic agonists
      thrombin and collagen, together with secretion of soluble APP (sAPP). A
      comparison between serum and plasma shows a 1.6-fold increase in Abeta levels and
      a 2.4-fold increase in sAPP levels in serum. This is consistent with the view
      that platelets are the primary source of circulating Abeta and APP. The release
      of platelet Abeta by physiologic stimuli suggests that it may play a role in
      platelet aggregation and coagulation or in the repair mechanisms associated with
      injury.

PMID- 9564891
TI  - Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic
      endocrine tumors.
AB  - Endocrine tumors of the parathyroid and pancreas are encountered either as
      sporadic type or as part of multiple endocrine neoplasia type 1 (MEN 1). A high
      frequency of the loss of heterozygosity (LOH) has been observed in tumors of the
      sporadic type in the locus of the MEN 1 gene, which has recently been cloned and
      designated the menin gene. It would be of great interest to determine whether
      somatic mutations in the menin gene are responsible for the sporadic endocrine
      tumors. For this purpose, we have investigated the menin gene mutations in 21
      sporadic parathyroid adenomas, 2 parathyroid carcinomas, 4 sporadic insulinomas,
      and 1 malignant VIP (vasoactive intestinal polypeptide)oma with WDHA (watery
      diarrhea, hypokalemia, and achlorhydria) syndrome, using PCR-single strand
      conformation polymorphism analysis and DNA sequencing. In none of these cases did
      the patient have a family history or other possible association with MEN 1. We
      have discovered somatic point mutations in two parathyroid adenomas (A340T and
      A541T), in one insulinoma (T429K), and in the malignant VIPoma (W198X). In
      addition, we have found two polymorphisms (D418D and V367V) in two parathyroid
      carcinomas and two parathyroid adenomas. Of these mutations and polymorphisms,
      three (A340T, T429K, and V367V) are first reported here, in the present article.
      Our results indicate that somatic mutations of the menin gene are responsible for
      a proportion of the sporadic parathyroid adenomas and pancreatic islet cell
      tumors.

PMID- 9564892
TI  - Evidence for apoptosis signal-regulating kinase 1 in the regenerating palatal
      epithelium upon acute injury.
AB  - Apoptosis signal-regulating kinase 1 (ASK1), a recently identified mitogen
      activated protein (MAP) kinase kinase kinase, is a key element in the mechanism
      of stress- and cytokine-induced apoptosis. However, pathophysiologic roles of
      ASK1 in vivo are poorly understood. In the present study, we analyzed the ASK1
      expression in injured rat palate using an immunohistochemical approach to
      investigate the roles of ASK1 during the process of wound healing. In the normal
      rat palatal epithelium, a weak cytoplasmic staining of ASK1 was observed in
      keratinocytes of the prickle cell layer. After mucoperiosteal injury of the
      palate, ASK1 was clearly observed in the suprabasal keratinocytes surrounding the
      wound. ASK1 expression was most evident at Day 2 after injury in the edge of the
      migrating epithelium. Thereafter, the intensity of ASK1 staining decreased
      gradually until the re-epithelialization was completed at Day 10 to 14. A
      staining with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end-labeling method identified a number of apoptotic keratinocytes in the
      suprabasal layers at the healing edge. Active induction of epithelial apoptosis
      was readily detectable from Day 5 after injury. In double-staining analysis, the
      temporal and spatial pattern of ASK1 expression correlated well with the
      appearance of apoptotic keratinocytes. p38 MAP kinase, a downstream component of
      ASK1, was found to be activated at the sites of ASK1 expression, suggesting that
      increased expression of ASK1 leads to activation of downstream MAP kinase
      signaling pathway in vivo. These results suggest a significant contribution of
      ASK1 to the epithelial apoptosis in the process of mucoepithelial wound repair.

PMID- 9564893
TI  - A novel monospecific IgG2/lambda-autoantibody with specificity for a
      mitochondrial antigen: evidence for an antigen-driven pathogenetic B-cell
      response in rheumatoid synovial tissue, induced by tissue alteration.
AB  - To elucidate the pathogenic role of synovial B cells in rheumatoid arthritis
      (RA), nine human IgG/lambda-secreting B-cell hybridomas from rheumatoid synovial
      tissue of a patient with definite RA were screened by enzyme-linked immunosorbent
      assay and indirect immunofluorescence on tissue cryosections for detection of
      antibodies against autoantigens. One IgG2/lambda monoclonal antibody (mAb) from
      the B-cell hybridoma ELG211/15/63 (= hybr63) exhibited intense immunofluorescence
      reactivity in the cytoplasm of chondrocytes and epithelial cells of the
      gastrointestinal tract, especially in parietal cells of gastric mucosa (human and
      mouse tissue), representing a mitochondrial pattern. This result was confirmed by
      morphometric analysis of immunoelectron microscopy data, exhibiting a
      significantly higher labeling density in mitochondria (p < or = 0.001) than in
      the cytoplasmic background, with predominant staining in the inner mitochondrial
      membrane and mitochondrial matrix (p < or = 0.05). Immunoblotting experiments
      carried out with gastric mucosa, and a mitochondrial protein preparation revealed
      two major proteins of 38 and 50 kd under reducing conditions. The analysis of the
      IgV(H) genes from this B-cell hybridoma showed highest homology to the human
      germline gene DP53 (96%). The IgV(L) region gave highest homology to the human
      germline gene DP5 (93%). In the complementarity-determining regions, residues of
      the H- and L-chain variable regions replacement mutations only indicated that
      this B-cell clone had been antigen-selected for its affinity (ratio of
      replacement to silent mutations: > or = 7). To analyze the in vivo expansion of
      the B-cell clone, primers specific for the V(H) to D to J(H) rearrangement of
      this B-cell hybridoma were used. Specific amplifications could be detected within
      part of the synovial tissue but not within the cells of the synovial fluid and
      peripheral blood of the patient. The ability of the IgG2/lambda mAb to induce an
      inflammatory reaction was tested by intraperitoneal application in severe
      combined immunodeficiency (SCID) mice, which resulted in an inflammatory,
      predominantly granulocytic infiltration of the peritoneum. Consequently,
      intrasynovial cell death or cartilage destruction seems to be a possible source
      of liberation of mitochondrial antigens, inducing a local, antigen-driven
      IgG2/lambda B-cell response with the ability to induce an inflammatory reaction.
      These data suggest that tissue destruction may serve as a source of arthritogenic
      antigens that perpetuate and amplify the local pernicious inflammatory process in
      RA synovialitis.

PMID- 9564894
TI  - P- and E-selectins are required for the leukocyte recruitment, but not the tissue
      swelling, associated with IgE- and mast cell-dependent inflammation in mouse
      skin.
AB  - Many studies, in both experimental animal and human systems, have indicated that
      P- and/or E-selectins may contribute importantly to the leukocyte recruitment
      that occurs in association with mast cell-dependent inflammatory responses. We
      used mice that genetically lack P-selectin (P -/-), E-selectin (E -/-), or both
      selectins (P/E -/-) to investigate the possible roles of these selectins in the
      IgE- and mast cell-dependent recruitment of neutrophils to the skin of mice. We
      found that a lack of either or both selectins had little or no effect on the
      extent of mast cell degranulation or the tissue swelling associated with these
      reactions. Moreover, a lack of either P- or E-selectin alone did not reduce the
      neutrophil infiltration at the reaction sites. However, mice lacking both P- and
      E-selectins exhibited an almost complete ablation of IgE- and mast cell-dependent
      neutrophil recruitment. These findings show that P- and E-selectins can express
      overlapping functions in leukocyte recruitment associated with IgE- and mast cell
      dependent cutaneous late-phase reactions in mouse skin, and that a lack of both
      selectins results in a virtual elimination of IgE-dependent leukocyte
      recruitment.

PMID- 9564895
TI  - Umbilical endothelial cell cultures: a model to study the endothelial lesion in
      preeclampsia in vitro.

PMID- 9564896
TI  - Globalization.

PMID- 9564897
TI  - International aspects of cardiac surgery.

PMID- 9564898
TI  - The Medicare program and thoracic surgery: crisis or opportunity?

PMID- 9564899
TI  - Long-term results after repeated surgical removal of pulmonary metastases.
AB  - BACKGROUND: Although surgical resection is accepted widely as first-line therapy
      for pulmonary metastases, few data exist on the surgical treatment of recurrent
      pulmonary metastatic disease. In a retrospective study, we analyzed patients who
      were operated on repeatedly for recurrent metastatic disease of the lung with
      curative intent over a 20-year period. METHODS: From 1973 to 1993, 396
      metastasectomies were performed in 330 patients. The study population included
      patients with any histologic tumor type who had undergone at least two (range, 2
      to 4) complete surgical procedures because of recurrent metastatic disease.
      Surgical and functional resectability of the recurrent lung metastases and
      control of the primary lesion served as objective criteria for reoperation. A
      subgroup of 35 patients that included patients with histologic findings such as
      epithelial cancer and osteosarcoma then was analyzed retrospectively to calculate
      prognosis and define selection criteria for repeated pulmonary metastasectomy.
      RESULTS: The 5- and 10-year survival rates after the first metastasectomy were
      48% and 28%, respectively. The overall median survival was 60 months. A mean
      disease-free interval (calculated for all intervals, with a minimum of two) of
      greater than 1 year was significantly associated with a survival advantage beyond
      the last operation. Univariate analysis failed to show size, number, increase or
      decrease in number or size, or distribution of metastases as factors related
      significantly to survival. CONCLUSIONS: Although patients with different
      histologic tumor types were included, the study population appeared to be
      homogeneous in terms of survival benefit and prognostic factors, and it probably
      represented the selection of biologically favorable tumors in which histology,
      size, number, and laterality are of minor importance. We conclude that patients
      who are persistently free of disease at the primary location but who have
      recurrent, resectable metastatic disease of the lung are likely to benefit from
      operation a second, third, or even fourth time.

PMID- 9564900
TI  - Microvascular permeability of the non-heart-beating rabbit lung after warm
      ischemia and reperfusion: role of neutrophil elastase.
AB  - BACKGROUND: The duration of warm ischemia and reperfusion injury is a major
      limiting factor in the setting of lung transplantation with non-heart-beating
      donors (NHBD). We hypothesized that reperfusion with neutrophil elastase
      inhibitor or leukocyte-depleted blood has an inhibitory effect on the ischemia
      reperfusion injury of NHBD rabbit lungs. METHODS: To assess the lung injury, we
      used a perfused rabbit lung model and measured the hemodynamic parameters and
      filtration coefficient. The rabbit lungs after hypoxic cardiac arrest for 30, 50,
      and 60 minutes were harvested at room temperature, and ventilated lungs were
      reperfused for 1 hour at a constant flow (120 mL/min). The group with 60 minutes
      of warm ischemia and hypoxia was further divided into three groups to determine
      the effects of leukocyte-depleted reperfusion or neutrophil elastase inhibitor,
      (1) no other special treatment, (2) reperfusion with leukocyte-depleted blood,
      and (3) administration of 10 mg of specific neutrophil elastase inhibitor. The
      lungs reperfused immediately after harvest from the heart-beating donor were
      regarded as the control. RESULTS: Sixty minutes of warm ischemia and hypoxia
      resulted in an increase in filtration coefficient (0.68+/-0.20 g x min(-1) x cm
      H2O(-1) per 100 g) compared with the control values of 0.13+/-0.03 g x min(-1) x
      cm H2O(-1) per 100 g. The increase in filtration coefficient after 60 minutes of
      warm ischemia and hypoxia in NHBD was remarkably suppressed by leukocyte
      depletion (0.23+/-0.07) and by neutrophil elastase inhibitor (0.21+/-0.08). The
      shunt fraction and histology results were also near normal. CONCLUSIONS: These
      results suggested that leukocyte depletion or treatment with neutrophil elastase
      inhibitor during reperfusion reduces alveolar-capillary damage caused by lung
      ischemia-reperfusion injury in the NHBD lung transplantation setting. This effect
      might be mediated by inhibition of neutrophil elastase activity or sequestration,
      and thus may lead to the increased availability of NHBD lungs.

PMID- 9564901
TI  - Comparison of conventional and wire mesh expandable prostheses and surgical
      bypass in patients with malignant esophagorespiratory fistulas.
AB  - BACKGROUND: Patients who present with malignant esophagorespiratory fistula
      continue to provide a significant palliative challenge to gastroenterologists and
      surgeons. METHODS: This retrospective series reviewed 29 patients treated with
      conventional prostheses (13 patients), expandable wire mesh-coated prostheses (12
      patients), and surgical bypass with esophageal exclusion (4 patients) between
      1982 and 1995. RESULTS: Improvement in dysphagia scores were comparable in all
      three groups. Fistula occlusion was more successful with expandable prostheses
      (92%) compared conventional prostheses (77%); however, reinterventions were
      required more commonly with expandable prostheses, which were also significantly
      more expensive on a unit cost basis. In selected patients in whom prosthesis
      placement either was inappropriate or failed, surgical bypass and esophageal
      exclusion was undertaken. These patients demonstrated good palliation with
      minimal morbidity and no mortality. CONCLUSIONS: Both conventional and expandable
      prostheses are safe and reasonably straightforward treatment modalities for
      patients with esophagorespiratory fistulas. Because of ease of insertion and
      large luminal diameter, expandable metal prostheses will see increasing use in
      treatment of these difficult patients; however, conventional prostheses will
      remain a good alternative, especially in patients with extrinsic esophageal
      compression. When stent placement is either unsuccessful or inadvisable,
      physiologically fit patients can undergo surgical bypass and esophageal exclusion
      with good palliation and minimal morbidity and mortality.

PMID- 9564902
TI  - Thoracoscopic operation for secondary pneumothorax under local and epidural
      anesthesia in high-risk patients.
AB  - BACKGROUND: Video-assisted thoracic operations usually require single-lung
      ventilation under general anesthesia. However, for high-risk patients with other
      underlying pulmonary diseases, one has to consider risks of general anesthesia
      itself. METHODS: Four high-risk patients (4 men; mean age, 73 years) with
      intractable secondary pneumothorax and other underlying pulmonary diseases were
      treated by video-assisted thoracic operations under local and epidural
      anesthesia. Absorbable polyglycolic acid sheets and fibrin glue were used to
      control the air leakage. RESULTS: The mean duration of the procedure was 108
      minutes. Pain and cough reflex were well controlled, and spontaneous breathing
      and hemodynamics were well maintained during the operation. The mean duration of
      the postoperative chest drainage was 5 days. No significant postoperative
      complication was encountered. No pneumothorax had recurred at a mean follow-up of
      16 months. CONCLUSIONS: Video-assisted thoracic operations can be performed
      safely under local and epidural anesthesia for the treatment of intractable
      secondary pneumothorax in high-risk patients. The air leakage can be controlled
      with the use of polyglycolic acid sheets and fibrin glue without bullectomy.

PMID- 9564903
TI  - Bronchopulmonary aspergilloma: a reappraisal.
AB  - BACKGROUND: Classically, most complications observed after operations for
      aspergilloma occurred in patients with sequelae of tuberculosis. Because the
      incidence of tuberculosis has declined over the past two decades, aspergilloma is
      expected to develop with increasing frequency in patients without previous
      tuberculosis. Therefore, our hypothesis was that operative outcome should have
      improved during the most recent years in comparison with our previous experience.
      METHODS: Operative outcome of 12 recently accrued patients was evaluated and
      compared with a historic control group of 55 patients, previously reported by the
      same center. RESULTS: As expected, only 17% of patients of the present series had
      a history of tuberculosis, compared with 57% in the former series.
      Postoperatively, there was no mortality. Major morbidity has decreased, although
      this difference is not statistically significant: bleeding decreased from 44% to
      9% of patients; space problems decreased from 47% to 18%; and prolonged hospital
      stay (>30 days) decreased from 32% to 9%. CONCLUSIONS: Our results support a
      trend toward improved postoperative outcome of operations for aspergilloma owing
      to a decreased incidence of aspergilloma growing in tuberculous cavitations.

PMID- 9564904
TI  - Pathogenesis of systemic air embolism during bronchoscopic Nd:YAG laser
      operations.
AB  - BACKGROUND: The occurrence of systemic air embolism during bronchoscopic
      neodymium:yttrium-aluminum garnet laser operations has been suspected. Here we
      describe its mechanism. METHODS: Two patients with embolic cardiac and neurologic
      complications after bronchoscopic neodymium: yttrium-aluminum garnet laser tumor
      ablation are described. A subsequent third patient was monitored for intracardiac
      and aortic air by transesophageal echocardiography. A review of the literature
      and safety recommendations are discussed. RESULTS: The appearance of systemic air
      emboli was related to the use of the laser fiber air coolant at high flow and
      resolved by decreasing the air flow. The presence of intracardiac and aortic air
      was associated with hypotension and inferior ischemic electrocardiographic
      changes. CONCLUSIONS: Systemic air embolism during bronchoscopic laser operations
      is a potentially catastrophic complication and is related to the use of gas
      cooled laser fibers and contact probes. We recommend using the noncontact mode
      whenever possible and maintaining the coaxial coolant air flow at the minimum
      level or using a fluid coolant if contact is necessary.

PMID- 9564905
TI  - Nitric oxide potentiates acute lung injury in an isolated rabbit lung model.
AB  - BACKGROUND: The effect of inhaled nitric oxide (NO) treatment on pulmonary
      function in the setting of adult respiratory distress syndrome is controversial.
      We examined the effect of inhaled NO on pulmonary function in an isolated rabbit
      lung model of oleic acid (OA)-induced acute lung injury. We hypothesized that NO
      would decrease pulmonary artery pressure and improve oxygenation. METHODS: Rabbit
      heart-lung blocks were isolated, flushed in vivo, harvested, and immediately
      perfused with whole blood and ventilated with 50% oxygen (O2). Pulmonary artery
      pressure was determined every 15 seconds for 60 minutes of perfusion. Oxygenation
      was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40,
      and 60 minutes after initiation of OA infusion. Rabbits were randomized into four
      study groups: saline control; OA control, which received a 20-minute infusion of
      50% OA/ethanol solution; NO treatment (20 ppm NO inhaled before OA infusion); and
      NO control, which underwent NO (20 ppm) pretreatment, followed by saline
      infusion. Pulmonary artery pressure, oxygenation (arteriovenous O2 difference),
      compliance, and wet/dry lung weight were determined. RESULTS: Pretreatment with
      NO caused significant increases in pulmonary artery pressure (NO treatment versus
      NO control and saline control; no significant difference between NO treatment
      group and OA control group), and did not improve oxygenation in our model.
      CONCLUSIONS: Contrary to our hypothesis, pretreatment with NO potentiates acute
      lung injury in our isolated lung model. There was significant exacerbation of
      pulmonary hypertension and no improvement in oxygenation. Further investigation
      of the possible deleterious effects of NO in acute lung injury are needed,
      especially in the early acute phases of this process.

PMID- 9564906
TI  - Bilateral lung volume reduction surgery via median sternotomy for severe
      pulmonary emphysema.
AB  - BACKGROUND: Lung volume reduction surgery either via sternotomy or by
      thoracoscopy has been demonstrated to be effective for selected emphysema
      patients in North America and Europe. The present study summarizes short-term
      results of bilateral lung volume reduction performed via median sternotomy for
      the first consecutive 39 patients with severe diffuse emphysema in Okayama,
      Japan, from July 1995 to February 1997. METHODS: There were 35 men and 4 women,
      and the age range was 54 to 74 years with a mean age of 65 years. All were former
      heavy smokers and none of them had alpha1-antitrypsin deficiency. Only 9 patients
      (23%) showed a bilateral upper lobe pattern of emphysema. The operation was done
      through a median sternotomy, and the most emphysematous portions were excised
      bilaterally with a linear stapling device fitted with strips of bovine
      pericardium to prevent air leakage. RESULTS: No operative death was encountered.
      The first 33 patients completed 3-month follow-up assessment, and their mean
      forced expiratory volume in 1 second had improved by 41% from 735 mL to 1,037 mL.
      Other parameters of pulmonary function tests, arterial blood gas analysis, 6
      minute walking distance, and dyspnea scale also had improved significantly. These
      improvements lasted for at least a year. CONCLUSIONS: Bilateral lung volume
      reduction surgery via median sternotomy is a safe and effective procedure for
      selected severe emphysema patients. Although the pattern of emphysema might be
      different between countries, the results in Japanese patients were similar to
      those previously reported in North American and European patients.

PMID- 9564907
TI  - MRI-radiofrequency tissue tagging in patients with aortic insufficiency before
      and after operation.
AB  - BACKGROUND: Magnetic resonance imaging tissue tagging is a relatively recent
      methodology that describes ventricular systolic function in terms of
      intramyocardial ventricular deformation. Because the analysis involves the use of
      many intramyocardial points to describe systolic deformation, it is theoretically
      more sensitive at describing subtle differences in regional myocardial fiber
      shortening when compared with conventional measures of ventricular function such
      as wall thickening. The objectives of this study were (1) to define sensitive
      indices of ventricular systolic deformation to assist the clinician in the
      surgical evaluation of patients with aortic insufficiency, and (2) to quantify
      differences in regional systolic deformation before and after surgery for aortic
      insufficiency. METHODS: Magnetic resonance imaging with tissue tagging was
      performed on 10 normal volunteers and 8 patients with chronic severe aortic
      insufficiency. Follow-up postoperative studies (5.4+/-1.1 months) were obtained
      in 6 patients who underwent Ross procedure (1 patient), David procedure (1), and
      St. Jude aortic valve replacement (4). RESULTS: There was no significant
      difference in fractional area change, overall circumferential shortening, or
      overall radial thickening among the normal group, the preoperative aortic
      insufficiency group, or the postoperative aortic insufficiency group. However, on
      a regional basis, there was a decrease in posterior wall circumferential strains
      in the postoperative aortic insufficiency group (29%+/-13% preoperative aortic
      insufficiency (n=6) versus 24%+/-12% postoperative aortic insufficiency (n=6),
      p=0.02). CONCLUSIONS: On regional analysis, there was a small but significant
      decrease in posterior wall circumferential shortening after operation. Magnetic
      resonance imaging tissue tagging is a sensitive and clinically applicable method
      of quantifying regional ventricular wall function before and after intervention
      for aortic insufficiency.

PMID- 9564908
TI  - Midterm results of free internal thoracic artery grafting for myocardial
      revascularization.
AB  - BACKGROUND: This study investigated the midterm results after free internal
      thoracic artery (FITA) grafting for coronary artery bypass grafting. METHODS:
      Between 1988 and 1995, coronary artery bypass grafting and postoperative graft
      angiography were performed in 337 patients, of whom 56 patients were treated with
      57 FITA grafts. We examined the postoperative graft patency of FITA grafts
      compared with in situ internal thoracic artery (IITA) grafts, and the late
      results in the patients receiving at least one FITA graft (FITA group) were
      compared with those in the patients receiving only IITA graft (IITA group).
      RESULTS: The early postoperative graft patency rate was 93.2% for the FITA grafts
      and 96.0% for the IITA grafts (not significant [NS]). Patients underwent
      sequential graft angiography at 29.5 months postoperatively (25 FITA and 89
      IITA). The late graft patency rate was 100% and 92.1%, respectively (not
      significant). The cardiac death-free survival rate at 5 years was 93.5% in the
      FITA group and 96.6% in the IITA group (not significant), and the angina-free
      survival rate at 5 years was 80.6% and 83.2%, respectively (not significant).
      CONCLUSIONS: The FITA provides late results comparable with those attained with
      IITA.

PMID- 9564909
TI  - Impact of retrograde cerebral perfusion with posterolateral thoracotomy on distal
      arch aneurysm repair.
AB  - BACKGROUND: Repair of distal aortic arch aneurysms is difficult to accomplish
      through a median sternotomy or left thoracotomy, and stroke and respiratory
      disorders often become lethal complications with the use of circulatory arrest.
      We investigated the use of retrograde cerebral perfusion with a posterolateral
      thoracotomy in the repair of distal arch aneurysms. METHODS: Thirty-eight
      patients underwent repair of a distal arch aneurysm. They were divided into three
      groups according to the method of surgical repair used. Sixteen patients (group
      I) underwent proximal anastomosis of the graft with the use of an aortic cross
      clamp. Eight patients (group II) underwent open proximal anastomosis with the use
      of retrograde cerebral perfusion (oxygenated blood perfusion through a superior
      vena cava cannula) and a median sternotomy and anterolateral thoracotomy.
      Fourteen patients (group III) also underwent open anastomosis with the use of
      retrograde cerebral perfusion (cerebral perfusion through blood returned to the
      right atrium with the patient in the Trendelenburg position) and a posterolateral
      thoracotomy. RESULTS: The operative mortality rate in group I was 25.0%; 4 of 16
      patients died of stroke, myocardial infarction, and intestinal necrosis. In group
      II, 3 of 8 patients (37.5%) died of respiratory failure and aortic dissection. In
      group III, only 1 of 14 patients (7.1%) died, as a result of heart failure.
      CONCLUSIONS: The use of retrograde cerebral perfusion with a posterolateral
      thoracotomy is an alternative method that minimizes the risk of stroke and
      respiratory failure during distal aortic arch operations.

PMID- 9564910
TI  - Beta-blockade as an alternative to cardioplegic arrest during cardiopulmonary
      bypass.
AB  - BACKGROUND: As an alternative to cardioplegic arrest, cardiac surgical conditions
      have been produced using beta-blocker-induced minimal myocardial contraction
      (MMC) during cardiopulmonary bypass. The technique of MMC involves the use of
      high-dose intravenous esmolol to suppress myocardial chronotropy and inotropy
      sufficiently to produce cardiac surgical conditions. The purpose of this study
      was to compare conventional crystalloid cardioplegic arrest with MMC in terms of
      ischemia avoidance, myocardial edema formation, and cardiac function. METHODS:
      Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to
      crystalloid cardioplegic arrest for 2 hours. Surgical conditions were produced in
      the other 6 dogs for 2 hours using intravenous esmolol without aortic clamping or
      cardioplegia. Arterial and coronary sinus lactate concentrations were determined
      as a gauge of myocardial ischemia. Myocardial water content was determined using
      microgravimetry and preload recruitable stroke work was determined using
      sonomicrometry and micromanometry. RESULTS: Significant lactate washout was
      demonstrated after cardioplegic arrest but not after MMC. Myocardial water
      content was significantly less during and after MMC compared with cardioplegic
      arrest (p < 0.05). Preload recruitable stroke work was decreased compared with
      baseline values in both groups (p < 0.05). CONCLUSIONS: In contrast to a previous
      study that involved 1 hour of MMC, in this study, ventricular function was
      decreased to the same extent as with cardioplegic arrest after 2 hours of MMC.
      This was attributed to the accumulation of ASL-8123, the primary metabolite of
      esmolol, which possesses beta-antagonist properties. Although postbypass
      ventricular function is similar in both groups, MMC appears to be superior in
      terms of ischemia avoidance and myocardial edema formation.

PMID- 9564911
TI  - Hypomagnesemia inhibits nitric oxide release from coronary endothelium:
      protective role of magnesium infusion after cardiac operations.
AB  - BACKGROUND: Postoperative hypomagnesemia is common in patients who have undergone
      cardiac operations and is associated with clinically significant morbidity
      resulting from atrial and ventricular dysrhythmias. Magnesium supplementation may
      increase the cardiac index in the early postoperative period. METHODS: The action
      of the magnesium cation on coronary vascular reactivity was studied. Segments of
      canine epicardial coronary artery were suspended in organ chambers to measure
      isometric force (95% O2/5% CO2, 37 degrees C). RESULTS: In coronary segments
      constricted with prostaglandin F2alpha (2 x 10[-6] mol/L), acetylcholine and
      adenosine diphosphate (10[-9] to 10[-4] mol/L) induced vasodilation in arteries
      with endothelium (n=10, each group; p < 0.05). Acetylcholine-mediated
      vasodilation was blocked by NG-monomethyl-L-arginine (10[-4] mol/L) and NG-nitro
      L-arginine (10[-4] mol/L), two inhibitors of nitric oxide synthesis from L
      arginine (n=10, p < 0.05). The removal of magnesium from the organ chamber
      solution impaired vasodilation in response to acetylcholine and adenosine
      diphosphate. However, normal endothelium-dependent vasodilation could be restored
      by return of magnesium to the bathing solution. Vascular relaxation in response
      to bradykinin (10[-9] to 10[-6] mol/L), which was found to induce endothelium
      dependent vasodilation independent of nitric oxide production, was unaffected by
      magnesium removal (n=10). CONCLUSIONS: Hypomagnesemia selectively impaired the
      release of nitric oxide from the coronary endothelium. Because nitric oxide is a
      potent endogenous nitro-vasodilator and inhibitor of platelet aggregation and
      adhesion, hypomagnesemia could promote vasoconstriction and coronary thrombosis
      in the early postoperative period.

PMID- 9564912
TI  - Soluble complement receptor type I limits damage during revascularization of
      ischemic myocardium.
AB  - BACKGROUND: This study was undertaken to determine whether suppression of
      complement activation with soluble human complement receptor type I reduces
      myocardial damage during the revascularization of ischemic myocardium. METHODS:
      In 20 pigs, the second and third diagonal coronary arteries were occluded for 90
      minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of
      reperfusion. In 10 pigs, soluble human complement receptor type I (10 mg/kg) was
      infused over 30 minutes before the period of coronary occlusion; 10 other pigs
      received no soluble human complement receptor type I. Complement activation was
      measured by total hemolytic complement activity (expressed as a percentage of
      preischemic values). Ischemic damage was assessed by changes in myocardial tissue
      pH, wall motion scores (range, 4=normal to -1=dyskinesia), and infarct size (area
      of necrosis versus area at risk). RESULTS: After 180 minutes of reperfusion,
      hearts treated with soluble human complement receptor type I had significantly
      less complement activation than nontreated hearts (1.1%+/-0.09% versus 7.8%+/
      0.04%, respectively; p < 0.002), less myocardial acidosis (-0.41+/-0.03 versus 
      0.72+/-0.03, respectively; p < 0.0001), higher wall motion scores (3.1+/-0.09
      versus 1.67+/-0.16, respectively; p < 0.0001), and smaller infarct size (24.6%+/
      2.0% versus 41%+/-1.3%, respectively; p < 0.0001). CONCLUSIONS: Complement
      inhibition with soluble human complement receptor type I significantly limits
      ischemic damage during the revascularization of acutely ischemic myocardium.

PMID- 9564913
TI  - Heart retransplantation: a 23-year single-center clinical experience.
AB  - BACKGROUND: The main causes of allograft failure after cardiac transplantation
      are primary graft dysfunction, intractable acute rejection, and coronary graft
      disease. Despite the important progress in the last several years in graft
      preservation, surgical techniques, immunosuppression, and treatment of coronary
      graft disease, retransplantation in selected cases is the only way to achieve
      long-term recipient survival. METHODS: We compare here in a case-control study 24
      retransplantations with 47 first transplants in patients matched for date of
      transplantation. RESULTS: Between 1973 and 1996, 1,063 patients underwent cardiac
      transplantation in our institution. In this cohort, 22 patients had a total of 24
      retransplantations (2 second-time retransplantations). The causes of
      retransplantations were primary graft failure (n=4), acute rejection (n=7),
      coronary graft disease (n=11), and miscellaneous (n=2). Survival at 1 and 5 years
      of patients with retransplantations is 45.5% and 31.2%, and survival of control
      patients is 59.4% and 38.8% (p=0.07). An interval between first transplantation
      and retransplantation shorter (n=11) or longer (n=13) than 1 year is associated
      with a 1-year survival of 27.3% and 61.5% and a 4-year survival of 27.3% and 46%,
      respectively (not significant). Intervals shorter than 1 year between first
      transplantation and retransplantation were exclusively secondary to primary graft
      failure or intractable acute rejection. CONCLUSIONS: In the face of lack of donor
      grafts, these and other data indicate that retransplantation should be considered
      cautiously, especially when the interval between the first transplantation and
      retransplantation is short.

PMID- 9564914
TI  - Easy harvesting of radial artery with ultrasonically activated scalpel.
AB  - BACKGROUND: The radial artery was proposed and then abandoned as a coronary
      artery bypass graft in the 1970s. Development of new pharmacologic antispasmodic
      agents and minimally traumatic harvesting techniques has led to a revival of the
      use of the radial artery in coronary artery bypass surgery. Usually the main
      reasons for the spasm are thermal injury caused by electrocautery and traumatic
      harvesting technique. METHODS: In our technique an ultrasonically activated
      scalpel (Harmonic Scalpel; Ultracision Inc, Smithfield, RI) was used for radial
      artery harvesting without using hemostatic clips for vessel side branches. The
      patients in the study were divided into two groups of 10 patients each. In the
      first group radial arteries were harvested with this technique, and in the second
      group with hemostatic clips, scissors, and minimal electrocautery. Harvesting
      time, frequency of spasm, and use of hemostatic clips were compared between the
      two groups. RESULTS: The Harmonic Scalpel decreased the harvesting time,
      frequency of spasm, and excessive use of hemostatic clips. CONCLUSIONS: Good
      coagulation capacity with markedly decreased use of hemostatic clips and
      minimized thermal injury offers the surgeon the ability to perform less
      traumatic, spasm free, and rapid radial artery harvesting.

PMID- 9564915
TI  - Endothelial-dependent dynamic and antithrombotic properties of porcine aortic and
      pulmonary valves.
AB  - BACKGROUND: In the present study, the endothelium-dependent antithrombotic and
      dynamic properties of porcine aortic (AoV) and pulmonary valves (PuV) were
      investigated. METHODS: Fifteen fresh AoV and 15 fresh PuV were obtained from 25 9
      month-old swines. The valves were examined for endothelial function by
      pharmacologic evaluation (with and without endothelium) of both the endothelial
      releasing capacity of prostacyclin and the endothelial-dependent dynamic response
      to relaxing (acetylcholine from 10[-10] mol/L to 10[-4] mol/L in AoV and PuV
      segments precontracted with norepinephrine [3 x 10(-6) mol/L]) and contracting
      (endothelin-1, from 10[-11] mol/L to 10[-5] mol/L; and NG-monomethyl-L-arginine,
      10[-4] mol/L) drugs. The ultrastructural integrity of the endothelial valve layer
      was also examined with transmission electron microscopy. RESULTS: Acetylcholine
      caused potent relaxation in both AoV and PuV specimens with, but not in those
      without, endothelium. Endothelin-1 produced a concentration-dependent tension
      increase in AoV and PuV with and without endothelium. However, the intrinsic
      activity of the peptide significantly increased in tissues without endothelium.
      NG-monomethyl-L-arginine evoked a progressive increase in resting tension of the
      preparations, but the AoV and PuV without endothelium were less sensitive to the
      inhibition of the nitric oxide generation. Aortic and pulmonary valves with an
      intact endothelium showed a spontaneous ability to release prostacyclin. The
      basal release of this lipidic autacoid significantly decreased in cardiac valves
      without endothelium. This phenomenon was observed in both basal conditions, and
      under stimulation with the aforementioned drugs. Transmission electron microscopy
      showed the perfect preservation of endothelial cells in all the preparations
      examined. CONCLUSIONS: Valvular endothelium of AoV and PuV seems to have similar
      antithrombotic and dynamic functions of vascular endothelium, actively
      participating in valvular homeostasis.

PMID- 9564916
TI  - Alterations in renal microcirculation during cardiopulmonary bypass.
AB  - BACKGROUND: This study was designed to investigate renal microvascular changes
      during cardiopulmonary bypass. METHODS: Kidneys were harvested from each of four
      groups of 6 pigs. Group A were anesthetized and heparinized only. The remaining
      three groups underwent cardiopulmonary bypass at 28 degrees C, group B for 30
      minutes and groups C and D for 120 minutes; group D had an additional 30 minutes
      of normothermic perfusion at the end of the experiment. Renal cortical blood flow
      was measured using radiolabeled microspheres. Microvascular morphology was
      defined by corrosion casting and scanning electron microscopy. RESULTS: In group
      A, renal vascular resistance was 61+/-5.1 mm Hg x mL(-1) x min(-1). This value
      decreased to 28+/-7.8 in group B and 25+/-4.0 in group C (p < 0.05), and
      increased in group D to 40+/-4.1 (p < 0.05 versus groups A, B, and C). Cortical
      thickness, as measured by microvascular casts in groups A, B, and C, was 33, 34,
      and 31 mm, respectively, with equal distribution of the resin to the superficial
      and deep cortex but was significantly reduced in group D to 22 mm (p < 0.05
      versus groups A, B, and C), with failure of the resin to fill the superficial
      cortical layer. Diameters of glomeruli as seen on the casts were 111+/-10.38
      microm in group A, 100+/-9.24 microm in group B, and 82+/-4.4 microm in group C
      (p < 0.05 group A versus group C). The glomeruli from group D were still
      significantly smaller than group A (93+/-10.35 microm, p < 0.05). Mean glomerular
      capillary diameters were 4.65+/-0.26 microm in group A, 3.9+/-0.16 microm in
      group B, 3.6+/-0.19 microm in group C, and 3.65+/-0.3 microm in group D (p < 0.05
      group A versus groups B, C, and D). CONCLUSIONS: Hypothermic nonpulsatile
      cardiopulmonary bypass decreased renal vascular resistance, but the superficial
      and deep layers of the cortex were perfused equally. Glomeruli were reduced in
      size because of capillary narrowing. This was consistent with diversion of blood
      through bypass channels. With restoration of normothermia, underperfusion of the
      superficial cortex occurred, with potential for damage to these nephrons during
      the increased metabolic demands of rewarming.

PMID- 9564917
TI  - Negative reexploration for cardiac postoperative bleeding: can it be therapeutic?
AB  - BACKGROUND: Reexploration of the mediastinum for bleeding is required in 3% to 7%
      of patients after cardiac operation, with many proving to have no surgically
      correctable cause. In spite of a "negative exploration," the bleeding often
      ceases. We propose the hypothesis that such a negative exploration can be
      therapeutic by reducing marked fibrinolytic activity in the mediastinal cavity.
      METHODS: Fibrinolytic activity in shed mediastinal blood was compared with that
      in the system blood in 5 patients after cardiac operation by measuring
      fibrinogen, fibrin degradation product, plasminogen activator inhibitor-1, and
      alpha2-antiplasmin levels. RESULTS: Fibrinolytic activity in mediastinal blood
      was markedly increased when compared with paired systemic venous blood. This was
      indicated by the mediastinal blood's lower fibrinogen levels (0.47 versus 1.91
      U/mL; p < 0.001), very high levels of fibrin degradation products (1,350 versus
      200 ng/mL; p < 0.05), and higher levels of plasminogen activator inhibitor-1
      (55.5 versus 28.1 ng/mL; p < 0.005). Decreased levels of alpha2-antiplasmin were
      also observed in the mediastinum (0.50 versus 0.61 U/mL; p < 0.05). CONCLUSIONS:
      Our data confirm that fibrinolytic activity can be extremely high in the
      mediastinum in response to clot formation. This may explain the hemostatic
      effects of a negative reexploration, where irrigation and the removal of clots
      may reduce the fibrinolytic process; this may allow the bleeding ends of
      capillaries and small vessels to thrombose. Decreased levels of alpha2
      antiplasmin observed suggest that lysine analogs, such as epsilon-aminocaproic
      acid, may have a beneficial role when locally delivered into the mediastinum.

PMID- 9564918
TI  - Arrest duration influences postcardioplegia electrophysiologic recovery and
      reperfusion arrhythmias.
AB  - BACKGROUND: This study tests the hypothesis that postcardioplegia
      electrophysiologic recovery is influenced by the duration of cardioplegic arrest.
      METHODS: Pigs were randomized to various durations of cardioplegic arrest (group
      I, 15 minutes; group II, 60 minutes; group III, 120 minutes). Electrophysiologic
      data included limb lead, atrial and ventricular epicardial, and ventricular
      endocardial electrocardiograms. Variables included times for earliest electrical
      activity and sinus rhythm; number of defibrillations; mechanism for reperfusion
      ventricular fibrillation; and time until last ventricular fibrillation. RESULTS:
      Time to last ventricular fibrillation was 73+/-8, 134+/-23, and 238+/-23 seconds
      for groups I, II, and III (mean+/-standard error of the mean; p < 0.05 between
      group III versus groups I and II). The number of defibrillations was 1.0+/-0.3,
      5.8+/-1.2, and 10.5+/-1.1 for groups I, II, and III (p < 0.05 between groups).
      The time to sinus rhythm was 66+/-8, 192+/-27, and 249+/-23 seconds for groups I,
      II, and III (p < 0.05 group I versus groups II and III). The most common
      mechanism for reperfusion arrhythmias was an accelerating ventricular tachycardia
      that initiated fibrillation (79 of 167 episodes). However, in many instances
      postdefibrillation amplifier saturation masked the initiation of reperfusion
      arrhythmias. CONCLUSIONS: Electrophysiologic recovery after cardioplegic arrest
      is influenced by the duration of cardioplegic arrest.

PMID- 9564919
TI  - Effect of skeletonizing dissection on the internal thoracic artery.
AB  - BACKGROUND: Skeletonization of the internal thoracic artery (ITA) produces
      greater length for coronary bypass grafting. We studied the effect of
      skeletonization on the morphology, histology, and tissue viability of the ITA
      wall. METHODS: Six mongrel dogs underwent unilateral ITA dissection; the
      contralateral ITA was the control. Study periods were 3 weeks (n=3) and 12 weeks
      (n=3). At sacrifice, the entire anterior chest wall was removed and dynamically
      fixed with formalin. Extensive histologic comparisons were performed on three
      tissue blocks taken from each ITA, 2, 8, and 24 cm from their origin. RESULTS:
      Flows at the end of the study were comparable to measurements taken during
      operation, immediately after skeletonization. Grossly, the ITA wall was not
      injured by skeletonization and there was no adventitial hematoma or bleeding from
      the sealed branch ends. Microscopic observations showed intact, normal wall
      structures. Histologic data showed no major significant difference between
      controls and skeletonized ITAs. CONCLUSIONS: Careful skeletonizing dissection is
      not detrimental to the integrity of ITAs, which justifies their use for
      myocardial revascularization.

PMID- 9564920
TI  - Surgical management of radiation-induced heart disease.
AB  - BACKGROUND: With the increasing population of patients with prior mediastinal
      irradiation, cardiac surgeons will encounter patients with radiation-induced
      damage to the heart and the great vessels. Awareness of the pathology and the
      surgical management is essential to provide optimal care for these patients.
      METHODS: Eight patients with radiation-induced heart disease were encountered in
      the last 10 years. After a brief clinical presentation, the surgical management
      of radiation-induced heart disease is reviewed. RESULTS: Radiation can affect all
      the structures in the heart, including the coronary arteries, the valves, and the
      conduction system. The pericardium is the most commonly involved, and the
      conduction system is the least involved. Pericardiectomy is quite effective in
      patients with symptomatic pericardial effusion or constriction. The coronary
      lesions are located predominantly in the ostial or proximal regions of the
      epicardial vessels. Percutaneous transluminal coronary angioplasty alone appears
      to have a high rate of restenosis. Surgical revascularization has good long-term
      results, and the internal mammary artery should be used if it is satisfactory.
      The aortic and mitral valves are more commonly involved than the tricuspid and
      pulmonary valves. Myocardial dysfunction predominantly affects the right
      ventricle and requires particular attention during cardiopulmonary bypass and in
      the postoperative period. Restoration of sinus rhythm is essential in view of
      stiffness of the ventricles. Flexibility in the surgical approach with selective
      use of thoracotomy will facilitate the surgical procedure in certain patients.
      CONCLUSIONS: Surgeons should be well versed in all the manifestations and the
      management of radiation-induced heart disease.

PMID- 9564921
TI  - Ulnar artery as a coronary bypass graft.
AB  - BACKGROUND: The ulnar artery has been used as a coronary bypass graft in 8
      patients when it was deemed unsafe to harvest the radial artery after evaluation
      of the arterial circulation in the forearm and hand. METHODS: The ulnar artery
      was removed from the lower three quarters of the forearm, along with its
      satellite veins. Dissection was commenced distally near the wrist and extended
      proximally to where the ulnar artery passed between the two heads of origin of
      the flexor digitorum superficialis. The artery was divided distally above the
      wrist joint and proximally at a point immediately below the origin of the common
      interosseus artery. RESULTS: Ten ulnar arteries were removed for use as coronary
      artery bypass grafts; two were rejected, one because of severe calcification and
      the other because of atherosclerotic occlusion. The remaining eight ulnar
      arteries were grafted successfully to coronary arteries other than the left
      anterior descending. No early hand or cardiac complications were observed.
      CONCLUSIONS: The ulnar artery is an alternative coronary artery bypass graft that
      may be used when the radial artery is dominant and cannot be removed without
      risk. The ulnar artery is in close proximity to the ulnar nerve and harvesting
      has the potential to injure the nerve. Therefore, until the use of the ulnar
      artery has been more fully evaluated it should be used only when other options
      have been exhausted.

PMID- 9564922
TI  - Accurate localization of mitral regurgitant defects using multiplane
      transesophageal echocardiography.
AB  - BACKGROUND: Appropriate patient selection for surgical repair of the mitral valve
      depends on the specific location and mechanism of regurgitation, which, in turn,
      has necessitated a more detailed method to accurately describe mitral pathology.
      This study tests a strategy of using multiplane transesophageal echocardiography
      to systematically localize mitral regurgitant defects and compares these results
      with the surgical findings. METHODS: Fifty patients with mitral regurgitation
      underwent intraoperative transesophageal echocardiography for the evaluation of
      mitral pathology and potential repair. Mitral regurgitant defects were localized
      using a systematic strategy and a simple nomenclature that divides each mitral
      valve into six sections (three sections per leaflet) and each prosthetic sewing
      ring into six sections (60 radial degrees = one section). RESULTS: Thirty-nine
      patients with native mitral valves were studied, for a total of 234 sections
      evaluated. Eighty-seven of these sections contained regurgitant defects by
      transesophageal echocardiography (mean number of regurgitant defects per valve,
      2.2; range, 1 through 6). There was agreement between the transesophageal
      echocardiographic and surgical localizations in 96% (224/234; p < 0.0001) of the
      sections. Eleven patients with prosthetic mitral valves were studied, for a total
      of 66 sections evaluated. Twenty-three of these sections contained paravalvular
      leaks by transesophageal echocardiography (mean number of leaks per prosthesis,
      2.1; range, 1 through 6). There was agreement between the transesophageal
      echocardiographic and surgical localizations in 88% (58/66; p < 0.001) of the
      sections. CONCLUSIONS: This transesophageal echocardiographic strategy provides a
      systematic method to accurately localize mitral regurgitant lesions and has the
      potential to improve the preoperative assessment of patients with significant
      mitral regurgitation.

PMID- 9564923
TI  - Allograft heart valve viability and valve-processing variables.
AB  - BACKGROUND: The impact of allograft valve viability on valve durability remains
      controversial. Analyses of our clinical results have demonstrated the superiority
      of the cryopreserved valve viable at the time of implantation over the 4 degrees
      C stored valve nonviable at the time of implantation. In this study, we
      quantitatively assessed the effects on viability of current and past valve
      processing protocols at The Prince Charles Hospital. METHODS: The viability of
      pulmonary valves was quantitatively analyzed by thin-layer autoradiography to
      assess the effects of donor type, antibiotics, and valve storage. RESULTS:
      Control valve segments obtained from beating-heart donor valves had a higher
      initial viability (0.92+/-0.02) than nonbeating-heart donor valves (0.66+/-0.03).
      Cryopreservation after low-dose antibiotic sterilization significantly reduced
      viability to 50% to 60% of the control, and in the presence of amphotericin B,
      viability dropped further to 10% to 36% of the control. After 7 days' storage at
      4 degrees C, viability was reduced to 2% of control and to 0% viability after 21
      days. CONCLUSIONS: For maximal preimplantation viability, valves should be
      procured as soon as possible after cessation of heart beat and should be
      cryopreserved if they are not to be clinically implanted within 1 to 2 days.
      Amphotericin B should not be used in conjunction with cryopreservation if
      viability is to be maximized.

PMID- 9564924
TI  - Mechanisms of cardiomyoplasty: comparative effects of adynamic versus dynamic
      cardiomyoplasty.
AB  - BACKGROUND: The apparent paradox seen in patients who have undergone dynamic
      cardiomyoplasty and shown substantial clinical and functional improvements with
      only modest hemodynamic changes may be due to inappropriate end points chosen for
      study, a result of incomplete understanding of mechanisms involved. The purpose
      of this study was to compare the relative role of the passive "girdling effect"
      and the dynamic "systolic squeezing effect" of the wrapped muscle in
      cardiomyoplasty. METHODS: The control group of 6 dogs underwent 4 weeks of rapid
      pacing (250 beats/min) to induce severe heart failure followed by 8 weeks of
      observation without rapid pacing. The trajectory of recovery in hemodynamics and
      cardiac dimensions was followed with echocardiography and Swan-Ganz catheters. In
      the "adynamic" cardiomyoplasty group (n=4), the left latissimus dorsi muscle was
      wrapped around the ventricles and allowed to stabilize and mature for 4 weeks.
      This was followed by rapid pacing and recovery as in the control group. In the
      "dynamic" cardiomyoplasty group (n=3), the same protocol for the adynamic group
      was followed except that a synchronizable cardiomyostimulator was attached to the
      thoracodorsal nerve of the muscle wrap. This allowed the latter to be transformed
      during the rapid-pacing phase and permitted dynamic squeezing of the muscle wrap
      to be generated by burst stimulation synchronized with cardiac contraction in a
      1:2 ratio. RESULTS: Baseline data were comparable in all groups prior to rapid
      pacing. After 4 weeks of rapid pacing, the left ventricular ejection fraction was
      higher in the adynamic (27.0%+/-3.9%; p < 0.05) and dynamic (33.3%+/-2.3%; p <
      0.02) cardiomyoplasty groups compared with controls (18.8%+/-8.3%). Similarly,
      ventricular dilatation in both systole and diastole was less in the adynamic
      (51.8+/-8.7 mL, [p < 0.002] and 38.2+/-7.2 mL [p < 0.001], respectively) and
      dynamic (62.0+/-7.2 [p < 0.02] and 41.3+/-3.5 mL [p < 0.005], respectively)
      cardiomyoplasty groups compared with controls. In the dynamic group, on and off
      studies were carried out after cessation of rapid pacing while the heart was
      still in severe failure, and they demonstrated a systolic squeezing effect in
      stimulated beats. Only this group recovered fully to baseline after 8 weeks.
      CONCLUSIONS: By reducing myocardial stress, both the passive girdling effect and
      the dynamic systolic squeezing effect have complementary roles in the mechanisms
      of dynamic cardiomyoplasty.

PMID- 9564925
TI  - Prospective trial of catheter irrigation and muscle flaps for sternal wound
      infection.
AB  - BACKGROUND: Sternal wound infection is a relatively rare but potentially
      devastating complication of open heart operations. The most common treatments
      after debridement are rewiring with antibiotic irrigation and muscle flaps. Here
      we present the results of a prospective trial to determine the appropriate roles
      of closed-chest catheter irrigation and muscle flap closure for sternotomy
      infection and to assess the effect of internal mammary artery bypass grafting on
      the outcome of each treatment modality. METHODS: Between 1990 and 1994, 5,658
      sternotomies were performed at the University of Washington Medical Center.
      Sternal dehiscence occurred in 43 patients, 25 of whom had infection (overall
      incidence, 0.44%). Because of the infrequency of this complication, a
      prospective, randomized trial was developed in which the initial approach to
      sternal dehiscence was rewiring and catheter irrigation. Muscle flaps were used
      as the primary treatment if the sternum could not be restabilized or as secondary
      treatment if catheter irrigation failed. Wound resolution, length of hospital
      stay, and complications were evaluated. RESULTS: Sterile dehiscences were
      successfully closed with irrigation in 17 of 18 patients; the other patient
      required flap closure. Of the 25 patients with infection, 19 had irrigation and
      6, closure with flaps primarily. In the group of infected patients, 17 of the 19
      who received irrigation also had internal mammary artery bypass grafting.
      Irrigation failed in 15 (88.2%) of these 17 patients, and salvage was
      accomplished with muscle flap closure. All 6 patients with infection who were
      closed primarily with muscle flaps had a successful outcome. Hospitalization
      averaged 10.2 days when muscle flaps were used primarily and 14.3 additional days
      for unsuccessful irrigation. When irrigation was successful, the hospital stay
      averaged 11.2 days. CONCLUSIONS: Catheter irrigation should be reserved for
      patients without infection or patients with infection but without internal
      mammary artery bypass grafts in whom dehiscence occurs less than 1 month after
      sternotomy. All others should have closure with muscle flaps.

PMID- 9564926
TI  - Deep sternal wound infection: risk factors and outcomes.
AB  - BACKGROUND: Deep sternal wound infection (DSWI) is a serious complication of
      cardiac operations performed by median sternotomy. We attempted to define the
      predictors of DSWI and to describe the outcomes of two treatment strategies used
      at our institution. METHODS: Retrospective review was performed using
      prospectively gathered data on 12,267 consecutive cardiac surgical patients from
      1990 to 1995. Chart review was performed on all patients in whom DSWI developed,
      and follow-up was obtained on 100% of these patients. RESULTS: Deep sternal wound
      infections developed in 92 patients (incidence 0.75%). Multivariable predictors
      for development of DSWI in all patients were (odds ratios and 95% confidence
      intervals in parentheses) (1) diabetes mellitus (2.6; 1.7 to 4.0) and (2) male
      sex (2.2; 1.3 to 3.9). In patients receiving coronary artery bypass grafting
      alone, independent predictors were (1) bilateral internal thoracic artery grafts
      (3.2; 1.1 to 8.9), (2) diabetes (2.7; 1.6 to 4.3), and (3) male sex (1.8; 0.9 to
      3.7). For all other patients, predictors were (1) age more than 74 years (3.3;
      1.1 to 10.1), (2) male sex (3.0; 1.1 to 8.1), and (3) diabetes (2.3; 0.9 to 5.8).
      Bilateral internal thoracic artery grafts increased the risk of DSWI in all
      subgroups of coronary artery bypass graft patients, particularly in diabetics who
      had a 14.3% incidence of DSWI after bilateral internal thoracic artery grafting.
      Patients with DSWIs received either sternal debridement with primary closure
      (n=45) or sternectomy with flap reconstruction (n=46). The 6-month freedom from
      adverse event rate (ie, readmission, reoperation, or death) was 76% for both
      groups of patients. CONCLUSIONS: Male sex and diabetes are predictors of DSWI in
      all cardiac surgical patients. Bilateral internal thoracic artery grafting may be
      contraindicated in diabetic patients.

PMID- 9564927
TI  - Early results of posterior leaflet folding plasty for mitral valve
      reconstruction.
AB  - BACKGROUND: Standard reconstruction for posterior mitral leaflet (PML) disease is
      quadrangular resection and annular plication; when the PML is excessively high, a
      sliding plasty is used. We have developed an alternative technique, a posterior
      leaflet folding plasty. It is performed by folding down the cut vertical edges of
      the PML. The central height of the PML is reduced, leaflet coaptation is moved
      posteriorly, and annular plication is unnecessary. METHODS: From March 1995 to
      August 1996, 26 (17.9%) of 145 patients undergoing mitral reconstruction had a
      posterior leaflet folding plasty. Concomitant procedures included anterior
      leaflet resection or resuspension and myotomy and myectomy. In 3 patients, the
      PML resection extended to a commissure. RESULTS: There was one death and no
      reoperations. The mean New York Heart Association class was improved from 2.4
      preoperatively to 1.4. There was no major postoperative mitral insufficiency in
      the 26 patients. Systolic anterior motion was transiently seen in 1 patient in
      whom left ventricular outflow tract obstruction was present preoperatively.
      CONCLUSIONS: The data demonstrate the safety and short-term efficacy of posterior
      leaflet folding plasty. This technique may help avoid systolic anterior motion
      after reconstruction of the PML.

PMID- 9564929
TI  - Calcium preconditioning in human myocardium.
AB  - BACKGROUND: Ischemic stress and other protein kinase C (PKC)-linked receptor
      stimuli can induce rapid cardiac protection against ischemia-reperfusion injury.
      We and others have demonstrated that exogenous calcium (Ca2+) pretreatment
      confers PKC-mediated cardiac functional and infarct protection in animal models,
      but it remains unknown whether Ca2+ preconditioning confers similar postischemic
      functional protection in human myocardium, and, if so, whether the mechanism is
      mediated by PKC. We postulated that Ca2+ preconditioning confers ischemic
      tolerance to human myocardium by a PKC-dependent mechanism. METHODS: Human atrial
      trabeculae were suspended in organ baths and paced at 1 Hz, and force development
      was recorded. After 90 minutes of equilibration, all trabeculae were subjected to
      ischemia (45 minutes) and reperfusion (120 minutes). Exogenous CaCl2 (3.0 mmol/L
      for 5 minutes) or vehicle (saline solution) was administered before simulated
      ischemia, with or without concurrent PKC inhibition (bisindolylmaleimide I, 150
      nmol/L). RESULTS: Ischemia-reperfusion resulted in decreased postischemic
      developed force, Ca2+ preconditioning protected human myocardium against ischemia
      reperfusion injury (p < 0.05 versus control ischemia-reperfusion), and concurrent
      PKC inhibition abolished the salutary effect of Ca2+ preconditioning in human
      myocardium (p < 0.05 versus Ca2+ preconditioning). CONCLUSIONS: Preconditioning
      with Ca2+ represents a potent means of accessing PKC-mediated protection of the
      human myocardium against ischemia-reperfusion injury.

PMID- 9564928
TI  - The safety of cardiac operations in the liver transplant recipient.
AB  - BACKGROUND: Advances in surgical techniques and immunosuppressive drugs have
      improved the survival of patients after orthotopic liver transplantation.
      Enhanced survival has resulted in an increased number of patients who require
      medical as well as surgical management of diseases. METHODS: To contribute to the
      sparse literature on the surgical aspects, we reviewed our experience with 15
      patients who underwent cardiac operation (1.25%) from a total of 1,200 liver
      transplant recipients at our center. The variables studied included the
      pretransplant cardiac evaluation, the interval from transplantation to cardiac
      operation, postoperative complications, the management of immunosuppression, and
      follow-up. The patients had a mean age of 52.9 years (range, 39 to 69 years) and
      13 of them (86.6%) were men. Multiple cardiac risk factors were present in all 15
      patients and chronic renal insufficiency was present in 7 patients. Cardiac
      operation was undertaken a mean of 30.4 months (range, 9 days to 62 months) after
      myocardial ischemia and valvular regurgitation had been ruled out at the time of
      transplantation. Myocardial revascularization was performed in 12 patients, 2 of
      whom underwent concurrent valve operation and 3 of whom underwent valve repair or
      replacement. Most patients had their immunosuppression regimen continued at
      baseline levels. RESULTS: There were no early deaths. Three patients had major
      complications and 4 had minor complications. There were no bleeding, infection,
      or healing complications. Postoperative renal parameters were persistently
      elevated in 5 patients and transiently elevated in 3. Liver function parameters
      were transiently elevated in 6 patients after the cardiac operation. No patient
      had hepatic rejection. A transient elevation or decrease in immunosuppressive
      drug levels was seen in 3 patients. Follow-up, obtained on all 15 patients,
      ranged from 6 to 83 months (mean, 26.5 months). There were 2 late deaths (13.3%),
      and 3 patients (25%) who underwent myocardial revascularization had recurrent
      angina. CONCLUSIONS: Cardiac operations can be undertaken safely in liver
      transplant recipients with good intermediate-term results. The immunosuppression
      regimen can be continued at preoperative levels with no need for stress-dose
      steroids. There were no hepatic complications among our patients, although some
      patients can experience worsening of renal failure.

PMID- 9564930
TI  - Monocyte tissue factor expression and ongoing complement generation in
      ventricular assist device patients.
AB  - BACKGROUND: Ongoing complement activation in patients with a ventricular assist
      device may contribute to observed hemostatic abnormalities and cellular
      aggregation by mediating leukocyte and platelet activation, formation of
      leukocyte-platelet conjugates, and the tissue factor pathway of coagulation.
      METHODS: Blood from 30 patients was collected before ventricular assist device
      implantation and during the implantation period. Plasma levels of thrombin
      antithrombin III complexes, C3a, and SC5b-9 were measured by commercial enzyme
      linked immunosorbent assay. Flow cytometry was used to measure circulating
      monocyte tissue factor expression and circulating monocyteplatelet and
      granulocyte-platelet conjugates. RESULTS: Thrombin-antithrombin III complex level
      and monocyte tissue factor expression peaked in the early postoperative period,
      with maxima occurring on postoperative days 5 and 3, respectively. Levels of C3a
      and SC5b-9 remained dramatically elevated over normal values for the duration of
      the study (6 and 5 times upper normal, respectively). Levels of monocyte-platelet
      conjugates were normal before implantation, decreased during the first 4
      postoperative days, and then increased and remained elevated. Levels of
      granulocyte-platelet conjugates were elevated over the normal range before
      implantation and remained elevated from postoperative days 3 to 21. A positive
      correlation was found between levels of SC5b-9 and granulocyte-platelet
      conjugates (Spearman R=0.66; p < 0.001), and between levels of C3a and thrombin
      antithrombin III complex (Spearman R=0.13; p=0.021). CONCLUSIONS: The data
      suggest a model in which complement mediates formation of leukocyte-platelet
      aggregates and may indirectly contribute to thrombin generation through monocyte
      tissue factor expression.

PMID- 9564931
TI  - Temporal relation of ATP-sensitive potassium-channel activation and contractility
      before cardioplegia.
AB  - BACKGROUND: Pharmacologic treatment using potassium-channel openers (PCOs) before
      cardioplegic arrest has been demonstrated to provide beneficial effects on left
      ventricular performance with subsequent reperfusion and rewarming. However, the
      PCO treatment interval necessary to provide protective effects during
      cardioplegic arrest remains to be defined. The present study was designed to
      determine the optimum period of PCO treatment that would impart beneficial
      effects on left ventricular myocyte contractility after simulated cardioplegic
      arrest. METHODS: Left ventricular porcine myocytes were assigned randomly to
      three groups: (1) normothermic control = 37 degrees C for 2 hours; (2)
      cardioplegia = K+ (24 mEq/L) at 4 degrees C for 2 hours followed by reperfusion
      and rewarming; and (3) PCO and cardioplegia = 1 to 15 minutes of treatment with
      the PCO aprikalim (100 micromol/L) at 37 degrees C followed by hypothermic (4
      degrees C) cardioplegic arrest and subsequent rewarming. Myocyte contractility
      was measured after rewarming by videomicroscopy. A minimum of 50 myocytes were
      examined at each treatment and time point. RESULTS: Myocyte velocity of
      shortening was reduced after cardioplegic arrest and rewarming compared with
      normothermic controls (63+/-3 microm/s versus 32+/-2 microm/s, respectively; p <
      0.05). With 3 minutes of PCO treatment, myocyte velocity of shortening was
      improved after cardioplegic arrest to values similar to those of normothermic
      controls (56+/-3 microm/s). Potassium channel opener treatment for less than 3
      minutes did not impart a protective effect, and the protective effect was not
      improved further with more prolonged periods of PCO treatment. CONCLUSIONS: A
      brief interval of PCO treatment produced beneficial effects on left ventricular
      myocyte contractile function in a simulated model of cardioplegic arrest and
      rewarming. These results suggest that a brief period of PCO treatment may provide
      a strategy for myocardial protection during prolonged cardioplegic arrest in the
      setting of cardiac operation.

PMID- 9564932
TI  - Should the aortic valve homograft be recryopreserved?
AB  - BACKGROUND: The number of homograft donors is limited and the once-thawed
      homograft may be unsuitable for the recipient and obliged to be wasted. The
      purpose of this study was to investigate the possibility of recryopreserving and
      using the once-thawed homograft for another patient. METHODS: Canine aortic valve
      leaflets were frozen to -80 degrees C by a programmed freezer, stored in liquid
      nitrogen, and thawed after 1 week. A subgroup of leaflets was left at 4 degrees C
      for 15 minutes, re-cryopreserved, and thawed after 1 week. Pathologic and flow
      cytometric evaluations were performed. RESULTS: After thawing, by pathology,
      alignment of the fibers was acceptably maintained but the membrane and cytoplasm
      of the fibroblast were damaged. These findings were not significantly aggravated
      even after rethawing. By flow cytometry, fibroblast viability was 90.7%+/-1.7%
      immediately after thawing, 87.6%+/-1.0% after thawing for 15 minutes at 4 degrees
      C, 63.7%+/-2.7% during refreezing at 0 degrees C, and 39.4%+/-4.3% after
      rethawing. CONCLUSIONS: From the standpoint of fibroblast viability, it is not
      possible to recryopreserve the once-cryopreserved and thawed aortic valve
      homograft.

PMID- 9564933
TI  - Conservative operation for infective endocarditis of the mitral valve.
AB  - BACKGROUND: Subvalvular preservation is necessary to maintain left ventricular
      function, but accidental retention of infected tissue could cause postoperative
      endocarditis. METHODS: We examined 71 consecutive patients who underwent
      operation for mitral endocarditis. Endocarditis was uncontrolled and active in 24
      patients, partially treated (unfinished antibiotic course) in 17, and healed in
      30. RESULTS: Valves were repaired in 17% versus 59% versus 63% and replaced with
      subvalvular preservation in 25% versus 6% versus 3% of the uncontrolled active,
      partially treated, and healed groups, respectively. Thirty-day mortality was 29%
      versus 0% versus 3.3% (p=0.003), total mortality was 46% versus 18% versus 17%
      (p=0.035), and complications-related mortality was 38% versus 11% versus 13%
      (p=0.054), respectively. There was a trend toward lower complications-related
      mortality with subvalvular preservation than without. Postoperative endocarditis
      occurred in 3 of 30 patients without and 1 of 41 patients with subvalvular
      preservation. CONCLUSIONS: Postoperative mortality in uncontrolled active mitral
      endocarditis remains high, but results are good with partially treated or healed
      endocarditis. Subvalvular preservation improves outcome, does not increase
      postoperative endocarditis rates, and should be performed whenever feasible.

PMID- 9564934
TI  - Temporary luminal arteriotomy seal for bypass grafting.
AB  - BACKGROUND: To enable off-pump coronary operations in a bloodless surgical field
      without ischemic complications, we developed and assessed a temporary luminal
      arteriotomy seal in a porcine carotid artery bypass graft model. METHODS: In 16
      consecutive pigs (25 kg, 32 anastomoses) the arteriotomy was sealed luminally by
      a polyurethane elliptic convex seal. Endothelial denudation, medial necrosis, and
      intimal hyperplasia were measured quantitatively and compared with those seen in
      conventionally sutured anastomoses. RESULTS: The median occlusive time upon
      insertion or retrieval was 90 and 82 seconds, including the arteriotomy and
      securing the anastomosis, respectively. Once properly positioned, the seal
      provided a bloodless arteriotomy in all anastomoses. Microsurgical suturing was
      performed without leakage of the seal and with unimpeded flow. In the recipient
      artery, endothelial denudation was limited to one third of its circumference. No
      medial necrosis was found. Intimal hyperplasia at heel and toe was not
      significantly different from that seen in conventionally sutured anastomoses.
      CONCLUSIONS: During end-to-side bypass grafting, the temporary luminal
      arteriotomy seal provided a bloodless surgical field without interfering with
      recipient artery blood flow and with minimal damage to the arterial wall.

PMID- 9564936
TI  - Impact of ultrafiltration on blood use for atrial septal defect closure in
      infants and children.
AB  - BACKGROUND: Infants and children undergoing open cardiac operations have a high
      incidence of blood product transfusion. Ultrafiltration has been shown to reverse
      hemodilution and improve myocardial function and hemodynamics after
      cardiopulmonary bypass (CPB). METHODS: The effect of ultrafiltration on the
      amount of blood transfusion and hospital charge in 39 consecutive patients who
      underwent elective atrial septal defect repair was examined. Patients in group I
      (n=26) had a conventional cardiopulmonary circuit prime with blood, whereas 13
      patients had bloodless prime (group II). Ultrafiltration was used immediately
      after weaning from CPB in group II. The patients in group I received blood
      products after discontinuation of CPB to achieve a hematocrit of 30%. The amount
      of blood product used, hematocrit immediately after CPB and on arrival in
      intensive care unit, postoperative hemodynamics and saturations, total operating
      room charge, blood charge, hospital stay, and hospital charge were compared.
      RESULTS: Mean body weight (15.8 kg in group I versus 17.5 kg in group II) and
      preoperative hematocrit values (35.6% in group I versus 34.2% in group II) were
      similar. Mean hematocrit immediately after CPB was 22% and 14% in group I and II,
      respectively (p < 0.0001). The mean hematocrit upon arrival to the intensive care
      unit was 34% in group I and 22% in group II (p < 0.0001). The amount of blood
      product transfusion was 32 mL/kg in group I and 3 mL/kg in group II patients (p <
      0.0001). The patients in group II had significantly less blood bank charges;
      however, operating room charges and total hospital charges were similar between
      the two groups. CONCLUSIONS: Elective atrial septal defect repair was performed
      with no blood product transfusion without increased morbidity or hospital stay.
      Ultrafiltration can be used to reverse hemodilution resulting from a bloodless
      CPB prime without an increase in hospital charge.

PMID- 9564935
TI  - Facile minimally invasive cardiac surgery via ministernotomy.
AB  - BACKGROUND: The public's and surgeons' perception of minimally invasive
      operations are frequently at odds. Nevertheless, real or perceived benefits may
      result from limiting skin and skeletal trauma. METHODS: Beginning in January
      1996, we began approaching most infant and pediatric open heart procedures
      through an upper sternal split incision using a 1- to 3-inch skin opening and
      then extended this technique using a 2.5- to 3.5-inch incision for adult aortic
      and mitral valve replacement. RESULTS: A total of 82 patients, 57 infants and
      children and 25 adults, have been operated on using this approach (age range,
      newborn to 81 years). Operations accomplished through ministernotomy have
      included aortic valvotomy, arterial switch, tetralogy of Fallot, atrial or
      ventricular septal defect closure, aortic valve replacement, mitral valve
      replacement and repair, redo aortic or mitral valve replacement, double valve
      replacement, aortic root replacement, and complex arch reconstruction. In adults,
      the sternum was divided and then a T incision was made at the second, third, or
      fourth intercostal space. The mitral valve was reached through the roof of the
      left atrium. In children, a lower sternal split was used for atrial septal defect
      repairs. All cannulas were introduced through the ministernotomy incision,
      eliminating femoral cannulation. No new instruments, retractors, or ports were
      used. Mediastinal drainage was accomplished through a Blake drain connected to
      Heimlich-valved grenade suction. All but 2 patients were extubated immediately.
      Hospital stay was from 1 to 20 days (median 2 days). Patient and family
      acceptance is very high. CONCLUSIONS: On the basis of this initial experience, we
      attempt all congenital cardiac and isolated adult valve operations through
      ministernotomy.

PMID- 9564937
TI  - Atrial septal displacement for repair of anomalous pulmonary venous return into
      the right atrium.
AB  - BACKGROUND: In the repair of anomalous connection of the pulmonary veins to the
      right atrium, the use of a baffle of pericardium to divert the pulmonary venous
      blood into the left atrium could cause pulmonary venous obstruction as a result
      of thickening of the pericardial patch. Anomalous pulmonary venous drainage to
      the right atrium caused by malposition of the atrial septum primum can be
      repaired by displacing the shifted septum primum to the normal position. METHODS:
      In 5 patients with total (n=2) or partial (n=3) anomalous pulmonary venous
      drainage into the right atrium, the septum primum was shifted toward the left
      atrium and the pulmonary veins drained into the anatomic right atrium despite
      their normal connection with the posterior wall of the left atrium. This method
      consisted of incision of the posterior edge of the atrial septum primum and
      displacement of the incised atrial septum between the anomalous pulmonary veins
      and both venae cavae. No patch was used. RESULTS: Postoperative echocardiography
      showed a wide pathway from the pulmonary veins to the left atrium with no
      stenotic portions. No atrial arrhythmias occurred after the operation.
      CONCLUSIONS: This technique may be advantageous because it allows for future
      growth of the route of the pulmonary venous pathway and avoids postoperative
      supraventricular arrhythmias.

PMID- 9564938
TI  - Direct reconstruction of the pulmonary artery during the arterial switch
      operation: an interesting surgical option with excellent hemodynamic results.
AB  - BACKGROUND: In transposition of the great arteries, reconstruction of the neo
      pulmonary artery is a challenging surgical detail during the arterial switch
      procedure. We present early and midterm clinical and hemodynamic results of a
      direct reconstruction of the pulmonary artery avoiding prosthetic and autologous
      material. METHODS: Between 1990 and June 1996, a total of 189 patients underwent
      the arterial switch procedure because of D-transposition of the great vessels. Of
      them, 47 underwent direct pulmonary artery reconstruction. Mean age at operation
      was 5.2+/-4.1 days and mean weight was 3.75+/-0.85 kg. Simple transposition of
      the great arteries was present in 13, transposition of the great arteries plus
      ventricular septal defect in 27, and more complex forms of transposition of the
      great arteries in 7 patients. The great vessels were side-by-side in 4 patients
      and in the anteroposterior position in 43 patients. The technique of direct
      pulmonary reconstruction includes extensive mobilization of both pulmonary artery
      branches into the hilum, posterior incision of the mean pulmonary artery into the
      bifurcation, and resuspension of the posterior commissure of the neo-pulmonary
      valve. A large anastomosis without any tension is then performed, using the
      anterior remnant aortic sinus of Valsalva to fit out the expected size of the neo
      pulmonary artery. RESULTS: Early mortality was 8.5% (4/47) in this particular
      group of patients. Postoperative echocardiography was performed before hospital
      discharge, 3 to 6 months postoperatively, and after a mean follow-up of 24
      months. Of the 43 survivors, 37 patients had a pressure gradient across the
      pulmonary valve of less than 15 mm Hg. Mild pulmonary stenosis (pressure gradient
      of 15 to 30 mm Hg) was present in 4 and more severe supravalvar stenosis
      (pressure gradient > 30 mm Hg) in 2 patients. After a mean follow-up of 36
      months, there was one redo operation to enlarge the right ventricular outflow
      tract. CONCLUSIONS: Direct reconstruction of the neo-pulmonary artery-avoiding
      autologous pericardium and prosthetic material-may represent an interesting
      option during the arterial switch operation when the great vessels lie in the
      anteroposterior position. This technique is simple, and the hemodynamic midterm
      results are very favorable. The incidence of postoperative supravalvar pulmonary
      stenosis is low, and there may be considerable potential for unlimited tissue
      growth.

PMID- 9564940
TI  - Saphenous vein graft growth 13 years after coronary bypass in a child with
      Kawasaki disease.
AB  - The presumed limited growth potential of saphenous vein grafts has led many
      authorities to discourage their use in young children. We documented excellent
      growth and patency of a saphenous vein graft 13 years after operation in a 7-year
      old child with coronary artery obstruction caused by Kawasaki disease.

PMID- 9564939
TI  - Left pulmonary artery kinking caused by outflow tract dilatation after
      transannular patch repair of tetralogy of Fallot.
AB  - BACKGROUND: Stenosis of the branch pulmonary arteries after tetralogy of Fallot
      repair can result from several mechanisms. In patients with free pulmonary
      regurgitation and right ventricular dilatation after transannular patch repair,
      we have observed that the pulmonary outflow tract can dilate and elongate craniad
      and rotate to the left, resulting in kinking and obstruction of the previously
      normal left pulmonary artery. METHODS: Ten patients referred for reoperation
      after tetralogy repair with severe pulmonary regurgitation and right ventricular
      outflow tract dilatation were found to have left pulmonary artery kinking. In 8
      of these patients kinking was the sole or partial cause of left pulmonary artery
      obstruction, whereas there was no documented obstruction in the other 2. All
      patients underwent right ventricular outflow tract reconstruction and left
      pulmonary artery repair with removal of the redundancy at the kink point.
      Patching alone is not an effective method of repair in this condition, because
      the mechanism of obstruction is not corrected and the patch material can become
      redundant and lead to recurrent obstruction. RESULTS: All patients underwent
      successful pulmonary outflow tract reconstruction. Left pulmonary artery kinking
      was corrected in all patients, and relief of obstruction was attained in the 8
      patients with stenosis. At follow-up ranging from 9 to 58 months, no patient has
      evidence of recurrent left pulmonary artery stenosis. CONCLUSIONS: Left pulmonary
      artery kinking should be suspected at long-term follow-up after tetralogy repair
      in patients with significant pulmonary regurgitation and right-sided dilatation,
      even if previous evaluations showed no evidence of left pulmonary arterial
      abnormality. Because unilateral obstruction caused by kinking may lead to
      asymmetric pulmonary flow, it can exacerbate pulmonary regurgitation and right
      ventricular dilatation, in effect accelerating the processes that led to kinking
      in the first place. Kinking can be relieved successfully with the techniques
      described in this report.

PMID- 9564941
TI  - Combined coronary bypass and liver transplantation: technical considerations.
AB  - Combined coronary artery bypass grafting and orthotopic liver transplantation was
      carried out successfully in a 58-year-old man with angina pectoris and end-stage
      liver disease. To date, only 2 similar cases have been documented worldwide
      whereby the transplantation was performed either during cardiopulmonary bypass or
      with femoral-to-axillary venovenous bypass initiated at the termination of
      cardiopulmonary bypass. In this report we describe our experience with a
      simplified one-exposure approach for the combined operation using cardiopulmonary
      bypass in tandem with percutaneous femoral-to-right atrial venovenous bypass.

PMID- 9564942
TI  - Inflammatory aneurysm of the ascending aorta.
AB  - The gold standard to clarify an acute pathology of the ascending aorta is
      transesophageal echocardiography or contrast-enhanced computed tomography.
      Neither of these methods led to the correct finding in our case of an
      inflammatory aneurysm of the ascending aorta. Both assessments resulted in the
      diagnosis of an acute dissection of the ascending aorta.

PMID- 9564943
TI  - Management of the atherosclerotic ascending aorta with endoaortic occlusion.
AB  - Application of an external cross-clamp to an atherosclerotic ascending aorta
      increases the risk of an embolic event and traumatic injury of the aorta.
      Currently, there are limited management options in these patients when the
      clinical situation requires cardiac arrest during an operation. We present our
      approach to these patients using the Heartport Endoaortic Clamp (Heartport,
      Redwood City, CA).

PMID- 9564944
TI  - Replacement of infected thoracic aortic prosthesis with a spiral composite vein
      graft.
AB  - We describe a case of a patient who had a ruptured aorta repaired by
      femorofemoral bypass with an interposition graft and subsequently had a graft
      infection. The patient was taken to operation and the old graft was removed. It
      was replaced by a spiral great saphenous vein graft. The patient has been
      followed up for 36 months with computed tomographic scanning, which has shown
      that the vein graft has not dilated.

PMID- 9564945
TI  - Natural history of a ventriculoatrial fistula after a gunshot injury in 1945.
AB  - We describe an exceptional case of a patient who suffered a penetrating heart
      injury from a gunshot wound in 1945 leading to a left ventricular-right atrial
      fistula. Despite the resulting left-to-right shunt the patient remained
      relatively asymptomatic for 50 years before the onset of congestive heart failure
      necessitated an operation.

PMID- 9564946
TI  - Transmyocardial laser revascularization in allograft coronary artery disease.
AB  - We used transmyocardial laser revascularization to treat accelerated cardiac
      allograft atherosclerosis in 2 patients. One patient received transmyocardial
      laser revascularization as sole therapy, the other as an adjunct to coronary
      artery bypass grafting. The systolic function improved in both patients, although
      the patient who had adjunctive transmyocardial laser revascularization died of
      systemic infection and renal failure on postoperative day 55. The second patient
      is alive and well 1 1/2 years after the laser procedure. We discuss 4 other
      patients who received transmyocardial laser revascularization treatment elsewhere
      in the United States. Transmyocardial laser revascularization has the potential
      to become important in the treatment of transplant atherosclerosis. Randomized
      clinical trials are warranted to assess the efficacy of transmyocardial laser
      revascularization in this setting.

PMID- 9564947
TI  - Combined TMR and mitral valve replacement via left thoracotomy.
AB  - Transmyocardial laser revascularization is an emerging technique for treatment of
      patients with coronary artery disease not amenable to standard revascularization
      by either percutaneous transluminal coronary angioplasty or coronary artery
      bypass grafting. Transmyocardial laser revascularization is typically performed
      as an isolated procedure on the beating heart, although it has been performed as
      an adjunct to conventional coronary artery bypass grafting in nongraftable
      territories. We report the use of transmyocardial laser revascularization in
      combination with mitral valve replacement via a left lateral thoracotomy for
      treatment of ischemic mitral regurgitation.

PMID- 9564948
TI  - Heterotopic pancreas of the esophagus associated with a rare type of esophageal
      atresia.
AB  - An infant with a rare type of esophageal/tracheal anomaly associated with
      heterotopic pancreas of the esophagus is herein reported. The upper pouch
      containing heterotopic pancreas reached 1.5 cm below the tracheal carina, and the
      distal esophagus connected to the trachea 2 cm above the tracheal carina and thus
      formed a partial duplication of the esophagus. Heterotopic pancreas of the
      esophagus is extremely rare, with only 7 cases previously reported. Here we
      report the combination of heterotopic pancreas and esophageal atresia with
      tracheoesophageal fistula.

PMID- 9564949
TI  - Long-term cardiovascular consequences of undiagnosed intralobar pulmonary
      sequestration.
AB  - We report the case of a patient with a congenital aortic valve stenosis
      associated with a long-term undiagnosed intralobar pulmonary sequestration. The
      important blood flow through the aberrant artery led to progressive congestive
      heart failure and severe hemoptysis at the age of 25 years. We demonstrate the
      regression of cardiac symptoms and left ventricular diameter after surgical
      resection of the sequestration.

PMID- 9564950
TI  - Right ventricular dysplasia may pose risk of ventricular rupture after cardiac
      operations.
AB  - We report the second case of rupture of the right ventricle secondary to right
      ventricular dysplasia after an otherwise uneventful coronary bypass graft
      operation. This suggests that right ventricular dysplasia may be a risk factor
      for ventricular rupture after cardiac operations.

PMID- 9564951
TI  - Bronchial carcinoid tumor metastatic to the breast.
AB  - We report a case of bronchial carcinoid that initially manifested as metastatic
      tumor in the breast. An exhaustive search for the primary tumor yielded the
      finding of a large right lung mass. Subsequent histopathologic examination of the
      resected lung and breast tissues confirmed the lung cancer as a primary tumor and
      the breast tumor as metastatic disease.

PMID- 9564952
TI  - Delayed presentation of traumatic parasternal lung hernia.
AB  - Traumatic lung herniation is an unusual clinical problem. This case report
      describes a morbidly obese individual who sustained significant chest trauma in a
      motor vehicle accident. Lung herniation was noted at the time of delayed
      respiratory failure necessitating ventilation. The significance of the lung
      hernia in this patient's respiratory failure is uncertain. The lung hernia was
      repaired surgically to relieve pain, prevent incarceration, and optimize
      respiratory function. After a brief period of postoperative ventilation, the
      patient recovered markedly and has been well since.

PMID- 9564953
TI  - Two-stage repair for aortic regurgitation with interrupted aortic arch.
AB  - We performed two-stage repair for a rare adult case of interrupted aortic arch
      with aortic regurgitation and sinus of Valsalva aneurysm. A lateroisthmic bypass
      was established with minimal thoracotomy and partial clamping of the descending
      aorta to preserve collateral circulation. This was followed by aortic root
      reconstruction with a prosthetic graft and valve for aortic regurgitation with
      sinus of Valsalva aneurysm. This less invasive two-stage repair for such a rare
      pathology may facilitate smooth recovery of the patient.

PMID- 9564954
TI  - Reversal of renal failure and paraplegia after thoracoabdominal aneurysm repair.
AB  - Repair of ruptured thoracoabdominal aortic aneurysms is complicated by high rates
      of perioperative paraplegia, renal insufficiency, and mortality. This report
      describes a patient with a ruptured thoracoabdominal aortic aneurysm in whom
      preoperative acute renal failure was reversed with hemodialysis, aortic
      replacement, and renal revascularization. Prompt cerebrospinal fluid drainage
      reversed delayed-onset postoperative paraplegia and led to immediate, complete
      neurologic recovery.

PMID- 9564955
TI  - Video-assisted repair of a traumatic intercostal pulmonary hernia.
AB  - A case of traumatic right lung herniation to an area of anterior costal sternal
      separation and right hemothorax is presented. Application of a thoracoscopic
      approach to a traumatic lung hernia of the chest wall in this case is discussed.

PMID- 9564956
TI  - Prostaglandin E1 from the tip of an intraaortic balloon catheter for lower limb
      ischemia.
AB  - A method to treat lower limb ischemia associated with the insertion of an
      intraaortic balloon catheter is herein reported. A low dose of prostaglandin E1
      was administered into the descending aorta continuously from the tip of the
      intraaortic balloon catheter. Immediately after the administration of
      prostaglandin E1 in patients whose lower limbs were ischemic due to obstruction
      with the catheter, the peripheral circulation of the ischemic limbs recovered
      with minimal changes in the systemic arterial blood pressure. This method is
      simple and noninvasive and was found to induce a satisfactory effect.

PMID- 9564957
TI  - Optimizing mitral valve exposure with conventional left atriotomy.
AB  - The standard surgical approach to the mitral valve is accomplished through a
      longitudinal incision in the left atrium, posterior and parallel to the
      interatrial groove. Many other surgical approaches have evolved. This report
      describes a technique of optimizing mitral valve exposure via the standard
      approach. These modifications are simple, do not lengthen the procedure, and
      usually obviate the need for more complex maneuvers.

PMID- 9564958
TI  - Atrial flap anastomosis: an alternative technique for orthotopic heart
      transplantation.
AB  - To combine the advantages of the standard technique and the bicaval technique of
      orthotopic heart transplantation, we use a muscular flap of recipient heart right
      atrium for connecting the superior vena cava with the donor heart right atrium.
      The results in respect to the maintenance of atrioventricular valve competence as
      well as atrial conduction are promising.

PMID- 9564959
TI  - Minimally invasive reversed Z sternotomy for aortic valve replacement.
AB  - The minimally invasive reversed Z sternotomy is a surgical approach for aortic
      valve operations that provides an excellent view of the aortic root and allows
      access to the right atrium. It confers the advantages of preservation of the
      sternocostal articulations and both internal thoracic arteries with no need to
      enter either pleural cavity. It facilitates aortic and atrial cannulation for
      cardiopulmonary bypass and allows access for a superior pulmonary vein cardiac
      vent.

PMID- 9564960
TI  - Simplified method for candidate selection for radial artery harvesting.
AB  - With the renewed interest in the use of autogenous radial arteries in coronary
      artery bypass grafting, concerns regarding vascular compromise and selection of
      patients have arisen. In this report, we describe a modification of Allen's test.

PMID- 9564961
TI  - Conversion from routine CPB to centrifugal mechanical assist by transaortic
      inflow cannulation of the left ventricle.
AB  - We describe a technique of conversion from cardiopulmonary bypass to centrifugal
      mechanical assist that consists of using the existing aortic cannula for outflow
      and inserting a cannula into the left ventricle through a Dacron tube and across
      the aortic valve for inflow.

PMID- 9564962
TI  - A mystery of Vladimir P. Demikhov: the 50th anniversary of the first
      intrathoracic transplantation.
AB  - Vladimir P. Demikhov was the first to perform intrathoracic transplantation of
      the heart alone, lung alone, and the heart and lungs in a warm-blooded animal and
      the first to perform an experimental coronary artery bypass operation with
      success. He designed the first mechanical cardiac substitute and was one of the
      first to use the vascular stapling device in experiments. In 1960 Demikhov
      published the world's first monograph dealing with the subject of thoracic
      transplantation. This monograph, Experimental Transplantation of Vital Organs,
      became a "bible of intrathoracic transplantation" and deserves the recognition of
      everyone who is interested in organ transplantation. However, to say only that
      Demikhov was the first in the world who performed these operations is to say
      nothing. It is important to describe the circumstances under which these
      operations were done to appreciate the true scale of his innovations.

PMID- 9564963
TI  - Cantrell's syndrome: a challenge to the surgeon.
AB  - We present a case of partial Cantrell's syndrome with ventricular septal defect,
      left ventricular diverticulum, dextrorotation of the heart, an anterior
      diaphragmatic defect, and a midline supraumbilical abdominal wall defect with
      omphalocele. At the age of 20 months, the patient underwent a successful cardiac
      surgical procedure. To detect risk factors and to define therapeutic strategies,
      we analyzed the spectrum and the frequency of malformations described in 153
      patients with Cantrell's syndrome. Despite modern surgical standards, Cantrell's
      syndrome represents a challenge to the surgeon because of the wide spectrum of
      anomalies, the severity of the abdominal and cardiac malformations, and the high
      mortality.

PMID- 9564964
TI  - As originally published in 1990: Sutureless ring graft replacement of ascending
      aorta and aortic arch. Updated in 1998.

PMID- 9564965
TI  - Intraluminal shunting for coronary bypass.

PMID- 9564966
TI  - Surgical removal of teletronics pacing wire from the right pulmonary artery.

PMID- 9564967
TI  - Extracorporeal membrane oxygenation support and cytokines.

PMID- 9564968
TI  - A proper name for the internal mammary artery?

PMID- 9564969
TI  - A feasible femoral cannulation method during cardiopulmonary bypass.

PMID- 9564970
TI  - Minimally invasive coronary artery bypass.

PMID- 9564971
TI  - Minimally invasive coronary artery bypass grafting: What is the best approach?

PMID- 9564972
TI  - Minimally invasive axillary-coronary artery bypass.

PMID- 9564973
TI  - Minimally invasive axillary-coronary artery bypass.

PMID- 9564974
TI  - Steroids for pulmonary metastases of thymoma.

PMID- 9564975
TI  - Video-assisted modified Abruzzini technique for bronchopleural fistula repair.

PMID- 9564976
TI  - Why do channels remain patent after transmyocardial laser revascularization?

PMID- 9564977
TI  - Comparative clinical study of inhaled beclomethasone dipropionate and
      triamcinolone acetonide in persistent asthma.
AB  - At this time, no placebo-controlled studies in the clinical literature compare
      the efficacy and safety of the most widely prescribed oral inhaled
      corticosteroids when dosed at their recommended daily doses. This study compared
      the efficacy and safety of beclomethasone dipropionate (BDP) 336 microg/day
      administered by metered dose inhaler (MDI) alone, and triamcinolone acetonide
      (TA) 800 microg/day by MDI with a built-in tube extender in adults with
      persistent asthma. METHODS: This 56-day, randomized, double-blind, double-dummy,
      placebo-controlled, multicenter trial was conducted in 328 adults with mild to
      moderately severe asthma (FEV1 50% to 90% of predicted while maintained on
      inhaled corticosteroids). Patients were seen at a baseline visit and on study
      days 28 and 56. Efficacy variables included pulmonary function tests, physician
      and patient assessments of asthma condition, and use of rescue medication.
      RESULTS: Statistically significant improvements from baseline in most efficacy
      measures were demonstrated for both active treatments versus placebo, and with
      the following exception were the same between active treatments: mean increase in
      FEV1 in the beclomethasone dipropionate group was statistically significantly
      greater than in the triamcinolone acetonide group on day 28. Throughout the
      study, BDP was statistically superior to TA with respect to mean change from
      baseline in total asthma symptom scores and for 3 of 8 weeks in reducing the mean
      average weekly use of rescue albuterol (the two active treatments were comparable
      for this variable at all other time points). Beclomethasone dipropionate and TA
      were comparable in safety. CONCLUSION: In adult patients with mild to moderately
      severe persistent asthma, treatment with BDP consistently conferred greater
      improvement from baseline in mean FEV1 than TA. This difference achieved
      statistical significance after 28 days of therapy but was not maintained to
      endpoint. Decreases in overall asthma symptom scores and in the use of rescue
      albuterol were statistically significantly greater for the BDP group compared
      with the TA group. Based on these findings, we conclude that BDP is at least as
      effective as TA in the treatment of persistent asthma in adults, and judged by
      some measures, may be superior.

PMID- 9564978
TI  - Skin test reactivity to indoor allergens as a marker of asthma severity in
      children with asthma.
AB  - BACKGROUND: Specific IgE responses to common indoor aeroallergens in children
      with asthma have been found to be associated with acute asthma. OBJECTIVE: The
      purpose of this study was to examine the association between asthma severity and
      skin test reactivity to four common indoor allergens. METHODS: The charts of 139
      asthmatic children, aged 5 to 18 years, seen in a pediatric allergy clinic were
      reviewed to obtain the results of skin tests to cat, dog, cockroach, and dust
      mite allergens, FEV1, anti-asthma medication requirements and demographic
      characteristics. Logistic regression for ordinal data was used to examine the
      association between skin test reactivity and asthma severity (mild, moderate or
      severe) as determined from FEV1 and medication usage. RESULTS: The rate of
      allergen sensitivities were dust mite 55%, cockroach 50%, cat 29% and dog 17%.
      Children with positive skin test to cat allergen were more likely to have a
      higher asthma severity rating than children with a negative cat allergen skin
      test [proportional odds ratio (OR) = 3.0, 95% confidence interval (CI) = 1.4 to
      6.1, P = .003]. This association remained significant after we controlled for
      skin test reaction to the other three allergens and various sociodemographic
      factors (adjusted OR = 3.0, 95% CI = 1.3 to 7.2, P = .013). The ORs for
      sensitivity to dog, cockroach, and dust mite allergen did not differ
      significantly from one, but children who were sensitized to all four allergens
      had an OR of 4.8 (95% CI = 1.3 to 18, P = .019) relative to children who were not
      sensitized to any of the four allergens. This association also remained
      significant after controlling for sociodemographic variables (P = .030).
      CONCLUSION: Children with combined sensitivity to cat, dog, dust mite, and
      cockroach allergens were at increased risk of having more severe asthma. Our data
      also suggest that sensitization to cat allergen per se is a risk factor for more
      severe disease in these asthmatic children.

PMID- 9564979
TI  - Nonpigmenting fixed drug eruption due to pseudoephedrine.
AB  - BACKGROUND: The nonpigmenting fixed drug eruption is a distinctive drug reaction
      characterized by large, tender and symmetric erythematous plaques that disappear
      with no residual pigmentation. METHODS: A case of a non-pigmenting fixed drug
      eruption due to pseudoephedrine is reported. RESULT: The reappearance of typical
      lesions at the same sites after oral challenge with 60 mg pseudoephedrine
      together with the absence of pigmentation confirm the diagnosis. CONCLUSION: A
      new case of proven nonpigmenting fixed drug eruption to pseudoephedrine is
      described.

PMID- 9564980
TI  - Aerobiologic and immunochemical studies on Borassus flabellifer pollen: evidence
      for a 90-kD allergen.
AB  - BACKGROUND: The pollen grains of Arecaceae have been proved to be a very common
      aeroallergen in India. Except for the pollen grains of Cocos nucifera, detailed
      information about the allergenicity of other dominant Indian palm pollen is not
      available. OBJECTIVES: To explore the aerobiologic and allergenic significance of
      the pollen of palmyra palm (Borassus flabellifer Linn.), one of the important and
      common palm trees in India, with a view to isolate and purify its major
      allergenic components. METHODS: The aerobiologic survey was performed
      continuously using Burkard volumetric and Rotorod samplers from July, 1994 to
      June, 1996 in a northern suburb of greater Calcutta. The allergenic potential of
      the pollen extract and different fractions were studied by skin prick tests
      (SPT). ELISA and ELISA inhibition experiments were performed with individual and
      pooled patient sera to detect the specific IgE level. By 2-step ammonium sulphate
      fractionation and gel filtration study, the allergic fraction Fr.IIA1 was
      isolated. Its molecular weight was determined by SDS-PAGE and homogeneity was
      confirmed by rocket and crossed immunoelectrophoresis using rabbit antisera.
      RESULTS: Pollen grains of B. flabellifer were found to be present in air from
      February to May and June contributing more than 7% of the total airborne pollen
      load of the study area. The pollen elicited maximum concentration at 19 to 20
      hours in the evening and at a height of 4 m from ground level. Skin prick testing
      of 455 respiratory allergic patients with whole pollen extract exhibited 31.64%
      positive response. After 2-step ammonium sulphate fraction and gel filtration, a
      fraction (Fr.IIA1) having remarkable allergenicity was isolated. In native and
      SDS-PAGE, it was found as a single protein component of 90 kD and as homogeneous
      in RIE and CIE. The soluble protein-carbohydrate analysis indicated the
      probability of the component to be a glycoprotein. CONCLUSION: The aerobiologic,
      clinical, and immunochemical, studies demonstrated that the pollen of B.
      flabellifer is a dominant aeroallergen to cause respiratory trouble in the area
      where these trees grow. The isolated 90-kD component is one of the major
      allergens present in the pollen extract.

PMID- 9564981
TI  - Routine and influenza vaccination rates in children with asthma.
AB  - BACKGROUND: Children with asthma may be at increased risk for low immunization
      rates given that they have recurrent illnesses that often result in acute care
      visits to their pediatrician, visits to the emergency room, admissions to the
      hospital, and visits to subspecialists, where immunizations are not routinely
      administered. OBJECTIVES: To assess immunization rates for routine and influenza
      vaccines in children with asthma and assess factors that may contribute to delay.
      METHODS: We conducted a cross-sectional survey of 117 children aged 6 to 48
      months with onset of asthma within the first 15 months of life. Subjects were
      recruited from an allergy and immunology clinic at an urban, tertiary care
      center. Those judged to have immunization delay did not have the required 4 DTP,
      3 OPV, and 1 MMR vaccine by age 24 months (4:3:1 series). Receipt of influenza
      vaccine was determined for eligible children with moderate to severe asthma.
      RESULTS: Seventy-four (80%) children had up-to-date immunizations at age 24
      months. Those with delay had fewer visits to a subspecialist than those who were
      up-to-date (1 versus 2 visits P = .010). Twenty-two (25%) of 87 eligible subjects
      received influenza vaccine. Recipients were more likely to have been hospitalized
      than nonrecipients (77% versus 49%, P = .022). CONCLUSIONS: Though the majority
      of young children with asthma were up-to-date for routine immunizations, only 25%
      of children with moderate to severe asthma received influenza vaccine. Greater
      efforts must be made by pediatricians and asthma subspecialists to ensure that
      children with moderate to severe asthma are immunized against influenza virus.

PMID- 9564982
TI  - Late asthmatic response in exercise-induced asthma.
AB  - BACKGROUND: There is a controversy over the occurrence of a late asthmatic
      response during exercise-induced asthma. While some workers have documented such
      a response as a genuine phenomenon, others have attributed this to drug
      withdrawal. OBJECTIVES: We carried out the present study to investigate whether a
      late asthmatic response occurs during exercise-induced asthma as a genuine event
      and, if so, what are the factors which determine its occurrence. METHODS:
      Sixteen, clinically stable asthmatic patients with laboratory-proven exercise
      induced asthma underwent a standardized exercise challenge on a bicycle
      ergometer. The airway response to exercise was studied by spirometry to measure
      FEV1. Spirometry was carried out before the exercise, at 4, 8, 15, 30, and 60
      minutes, and then hourly for the next 7 hours. Spirometry was also done
      repeatedly as above on a non-exercise control day, four to seven days earlier.
      RESULTS: Eight (50%) subjects developed a second fall of greater than 10% in
      FEV1, three to eight hours after recovery from the early response. The late fall
      in FEV1 after exercise was significantly greater than the spontaneous decay of
      lung function at the corresponding clocktime on the non-exercise control day. The
      dual responders did not differ from those with isolated early responses with
      respect to age, duration and severity of asthma, treatment requirements,
      peripheral blood eosinophilia, and atopic status. Baseline FEV1 and maximum fall
      in FEV1 during the early response, and the rate of its development and recovery
      from it were also similar. Among the dual responders, the late response was not
      related to the baseline FEV1 or to the intensity of the early response.
      CONCLUSIONS: A late asthmatic response is a genuine phenomenon in exercise
      induced asthma. Its occurrence cannot however be predicted by any clinical or
      physiologic factors.

PMID- 9564983
TI  - Circadian rhythm of cutaneous hypersensitivity reactions in nocturnal asthma.
AB  - BACKGROUND: Diurnal variation in mast cell discharge may play a central role in
      the early morning fall in peak expiratory flow rate (PEFR) in nocturnal asthmatic
      patients. METHODS: We tested the hypothesis that there is a circadian rhythm in
      mast cell response to allergen in 15 patients with nocturnal asthma by measuring
      the magnitude of cutaneous hypersensitivity reactions at 0600, 1200, 1800, and
      2400 hours. Pre-admission, prick skin testing on the ventral aspect of the
      forearm to various allergens was performed. The allergen producing the largest
      wheal was tested at six sites on one forearm. Response was quantified after 20
      minutes by measuring the area of the wheal produced using planimetry. Every six
      hours the skin testing was repeated at six new sites on alternating forearms. The
      average area of the six wheals was calculated and recorded at each time. The
      prick skin technique was used at all times. RESULTS: Maximal reactions occurred
      in 10 of the 15 patients at noon (P = .031, Friedman's two way analysis of
      variance). In these 10 patients wheal area at the time of maximum reactivity was
      on average 3.3-fold higher than at the time of minimum reactivity. The mean wheal
      areas for all 15 patients at 0600, 1200, 1800, and 2400 hours were 34 mm2, 42
      mm2, 34 mm2, and 35 mm2 respectively. CONCLUSIONS: These observations support the
      concept of a circadian rhythm in mast cell activity in patients with severe
      nocturnal asthma.

PMID- 9564984
TI  - Evaluation of the potential cardiotoxicity of the antihistamines terfenadine,
      astemizole, loratadine, and cetirizine in atopic children.
AB  - BACKGROUND: Adverse cardiac effects have been related to the use of H1-receptor
      antagonists terfenadine and astemizole. OBJECTIVE: We have investigated the
      cardiac effects of the H1-receptor antagonists terfenadine, astemizole,
      loratadine and cetirizine, used in recommended doses, concomitantly or not with
      the antibiotic erythromycin. METHODS: A group of 80 children aged 5 to 12 years
      was studied. All children had been diagnosed with perennial allergic rhinitis
      based on symptoms, clinical signs and a positive immediate skin test to
      Dermatophagoides pteronyssinus. The children had no personal history of cardiac
      disease or hepatic dysfunction, and they had a normal electrocardiogram (ECG) at
      the beginning of the study. Forty children had allergic rhinitis and sinusitis,
      and were assigned to subgroups of ten children who received terfenadine,
      astemizole, loratadine, or cetirizine, concomitantly with erythromycin, for 14
      days. Erythromycin was started to treat presumed bacterial infection in children
      with complete radiologic opacification of the maxillary sinus(es). The remaining
      40 children had no sinusitis, and were assigned to subgroups of 10 children who
      received terfenadine, astemizole, loratadine, or cetirizine for 14 days. RESULTS:
      No significant changes in the QT interval and QTc (QT corrected by Bazzett's
      equation) were observed among children who received astemizole, loratadine or
      cetirizine, with or without erythromycin. Children who have received terfenadine
      and erythromycin showed significantly prolonged QT interval (mean pretreatment
      and posttreatment values 0.32s and 0.34s, respectively). Analysis of the QTc
      interval, however, showed no significant differences in the group treated with
      terfenadine and erythromycin (mean values 0.39s and 0.39s, respectively).
      CONCLUSIONS: Our results show that H1-receptor antagonists terfenadine,
      astemizole, loratadine and cetirizine, administered with or without erythromycin,
      to atopic children in recommended doses, do not induce adverse cardiac effects.
      Although the association between terfenadine and erythromycin has caused a
      statistically significant increase in QT interval measurements, the magnitude of
      these changes was below levels considered cardiotoxic or clinically relevant.

PMID- 9564985
TI  - Severe acute asthma in a community hospital pediatric intensive care unit: a ten
      years' experience.
AB  - BACKGROUND: The clinical literature on the incidence and subsequent mortality of
      asthma has come primarily from the experiences of large tertiary referral
      centers, particularly in Western Europe and North America. Consequently, very
      little has been published on the incidence, management, and outcome of asthma in
      smaller, community-based intensive care units. OBJECTIVES: The purpose of this
      study was to explore the course and outcome of children with acute severe asthma
      treated within a community hospital PICU compared with those described in the
      literature from larger tertiary referral centers. DESIGN: A retrospective
      analysis of 49 asthmatic children admitted to the Pediatric Intensive Care Unit
      (PICU) over a 10-year period was performed. MEASUREMENTS AND RESULTS: The mean
      age was 5.2 years (range 2 months to 16 years), and the male:female ratio was
      3:1. Duration of symptoms prior to admission to hospital was less than 24 hours
      in 60.4% of the patients. The majority of patients was not treated with either
      inhaled or oral steroids before admission. Drugs used in the PICU included
      nebulized beta2-agonists, theophylline, steroids, intravenous salbutamol, and
      intravenous isoproterenol. Although a pharmacologic approach was successful in
      the majority of patients, intubation and mechanical ventilation were necessary
      for progressive hypercapnea, exhaustion, and cardiorespiratory arrest in 11/49 of
      these patients. The average stay in the ICU for our patient group was 2.4 days.
      Intubated patients had a mean average stay of 3.5 days. Two patients had
      pneumothorax related to positive pressure ventilation, requiring chest tube
      insertion for drainage. There were no deaths among the 49 patients admitted to
      our PICU. CONCLUSIONS: These data show that for acute severe asthma, outcome is
      comparable in a community PICU to a tertiary referral institution. We conclude
      that early ICU admission along with close monitoring is important in reducing
      morbidity and mortality in children with severe asthma.

PMID- 9564986
TI  - Malignant cough equivalent asthma: definition and case reports.
AB  - BACKGROUND: Cough equivalent asthma is a cause for chronic cough and usually
      responds to corticosteroid therapy. Oral corticosteroids are employed in a
      diagnostic-therapeutic trial and inhaled corticosteroids are employed in
      maintenance therapy. In certain cases the cough may be especially severe and
      require escalated doses of oral corticosteroids for initial control. This is
      labeled malignant cough equivalent asthma. OBJECTIVE: To define malignant cough
      equivalent asthma, provide two case reports, and identify features that should
      alert physicians to consider the possibility of malignant cough equivalent
      asthma. CASE REPORTS: We report two patients who presented complaining of chronic
      cough that was disruptive of sleep and normal activities, and in one patient
      prompted an emergency room visit and later hospitalization. The patients
      underwent evaluation with history, physical examination, and laboratory testing
      as indicated. Other causes for chronic cough were ruled out by appropriate
      testing, or were treated, and patients did not respond to usual corticosteroid
      treatment for cough equivalent asthma. These patients were considered to have a
      more severe form of cough equivalent asthma and did respond to treatment with
      higher doses of oral corticosteroids. CONCLUSION: Malignant cough equivalent
      asthma is a cause of chronic cough that is disruptive to sleep or normal
      activities, may lead to emergency room visits or hospitalization, and requires
      escalated doses of oral corticosteroids for initial control.

PMID- 9564987
TI  - Combination drug therapy for the prevention of exercise-induced
      bronchoconstriction in children.
AB  - BACKGROUND: Sequential administration of a beta-agonist and cromolyn or
      nedocromil before exercise is recommended for patients whose symptoms are not
      controlled by beta-agonists alone; however, this practice reduces compliance.
      OBJECTIVE: To evaluate the effectiveness of a new pre-combined aerosol
      formulation (salbutamol and nedocromil) in preventing exercise-induced
      bronchoconstriction and to compare it to salbutamol alone. METHODS: Twelve
      children with asthma were studied in a double-blind, double-dummy, randomized,
      crossover, placebo-controlled design to compare the protective effect of
      salbutamol and a new pre-combined salbutamol/nedocromil formulation against
      exercise-induced bronchoconstriction. The drugs were delivered by a metered-dose
      inhaler (salbutamol, 200 microg; salbutamol/nedocromil, 200 microg/4 mg; placebo,
      2 puffs) 20 minutes before exercise. RESULTS: Both active drugs were
      significantly more protective than placebo but there was no difference between
      them. Complete protection was obtained in 12/12, 10/12, and 1/12 subjects for the
      salbutamol/nedocromil combination, salbutamol alone and placebo, respectively.
      CONCLUSIONS: Although inhaled beta-agonists alone are highly efficacious in
      preventing exercise-induced bronchoconstriction, a minority of patients exists
      for whom a combined treatment with salbutamol and nedocromil is advantageous.
      This group may represent a subpopulation of subjects who release more, or
      different, mediators in response to exercise.

PMID- 9564988
TI  - Open-label assessment of levofloxacin for the treatment of acute bacterial
      sinusitis in adults.
AB  - PURPOSE: To evaluate the efficacy and safety of levofloxacin (500 mg orally once
      daily for 10 to 14 days) in treating adult outpatients with acute bacterial
      sinusitis. PATIENTS AND METHODS: A total of 329 patients enrolled in the study at
      24 centers. All patients had a pre-therapy Gram's stain and culture of sinus
      exudate obtained by antral puncture or nasal endoscopy. Clinical response was
      assessed on the basis of signs and symptoms and sinus radiograph or computed
      tomography results. Microbiologic cure rates were determined on the basis of
      presumed plus documented eradication of the pre-therapy pathogen(s). RESULTS: The
      most common pathogens were Haemophilus influenzae, Streptococcus pneumoniae,
      Staphylococcus aureus, and Moraxella catarrhalis. Of 300 clinically evaluable
      patients, 175 (58%) were cured and 90 (30%) were improved at the post-therapy
      evaluation, resulting in a clinical success rate of 88%. Thirty-five patients
      (12%) clinically failed treatment. The microbiologic eradication rate (presumed
      plus documented) among 138 microbiologically evaluable patients was 92%.
      Microbiologic eradication rates (presumed plus documented) of the most common
      pathogens ranged from 93% (M. catarrhalis) to 100% (S. pneumoniae) at the post
      therapy visit. All but one of the 265 patients who were cured or improved at post
      therapy returned for a long-term follow-up visit; 243 (92%) remained well 4 to 6
      weeks after therapy; and 21 (8%) had a relapse of symptoms. Adverse events
      considered to be related to levofloxacin administration were reported by 29
      patients (9%). The most common drug-related adverse events were diarrhea,
      flatulence, and nausea; most adverse events were mild to moderate in severity.
      CONCLUSION: The results of this study indicate that levofloxacin 500 mg once
      daily is an effective and safe treatment for acute bacterial sinusitis.

PMID- 9564989
TI  - Rising stroke rates spur efforts to identify risks, prevent disease.

PMID- 9564991
TI  - Two generations of data aid Framingham's focus on genes.

PMID- 9564992
TI  - Study says stay calm and halve risk of stroke.

PMID- 9564990
TI  - A "family heirloom" turns 50. Interview by Rebecca Voelker.

PMID- 9564993
TI  - From the Centers for Disease Control and Prevention. Tobacco use among high
      school students--United States, 1997.

PMID- 9564994
TI  - From the Centers for Disease Control and Prevention. One thousand days until the
      target date for global poliomyelitis eradication.

PMID- 9564995
TI  - A national action plan to meet health care quality information needs in the age
      of managed care.
AB  - Concerted national action is needed to meet the growing demand for health care
      quality information among all health care stakeholders. We propose a coordinated
      national network of independent, public-private quality measurement alliances
      established through strong purchaser and consumer leadership at the state,
      regional, or local levels. These independent alliances could assume a variety of
      organizational forms, but all would undertake specific quality measurement and
      consumer information projects to meet local health care market needs by drawing
      on various combinations of the emerging national standardized quality measures.
      Local implementation of quality measures based on national standards will
      facilitate cross-market benchmarking and multistate comparisons useful not only
      to state and local market constituencies, but to national employers, health
      plans, provider organizations, and the federal government as well. Successful
      models of such alliances already exist that demonstrate the feasibility of this
      national strategy, but concerted national leadership and federal matching funding
      will be needed to meet the scope of implementation required in markets across the
      country.

PMID- 9564996
TI  - Deciding life and death in the courtroom: debate and clarification.

PMID- 9564997
TI  - Deciding life and death in the courtroom: debate and clarification.

PMID- 9564998
TI  - Deciding life and death in the courtroom: debate and clarification.

PMID- 9564999
TI  - Deciding life and death in the courtroom: debate and clarification.

PMID- 9565000
TI  - Modifying coronary heart disease risk factors in children: is it ever too early
      to start?

PMID- 9565001
TI  - Modifying coronary heart disease risk factors in children: is it ever too early
      to start?

PMID- 9565002
TI  - More on thrombolytic therapy for acute stroke.

PMID- 9565003
TI  - False-negative qualitative troponin T.

PMID- 9565004
TI  - Interferon for melanoma: another application of immunopharmacology.

PMID- 9565005
TI  - The costs of triple-drug anti-HIV therapy for adults in the Americas.

PMID- 9565006
TI  - Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute
      ischemic stroke: a randomized controlled trial. The Publications Committee for
      the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators.
AB  - CONTEXT: Anticoagulation with unfractionated heparin is used commonly for
      treatment of acute ischemic stroke, but its use remains controversial because it
      has not been shown to be effective or safe. Low molecular weight heparins and
      heparinoids have been shown to be effective in preventing deep vein thrombosis in
      persons with stroke, and they might be effective in reducing unfavorable outcomes
      following ischemic stroke. OBJECTIVE: To test whether an intravenously
      administered low molecular weight heparinoid, ORG 10172 (danaparoid sodium),
      increases the likelihood of a favorable outcome at 3 months after acute ischemic
      stroke. DESIGN: Randomized, double-blind, placebo-controlled, multicenter trial.
      SETTING AND PARTICIPANTS: Between December 22, 1990, and December 6, 1997, 1281
      persons with acute stroke were enrolled at 36 centers across the United States.
      INTERVENTION: A 7-day course of ORG 10172 or placebo was given initially as a
      bolus within 24 hours of stroke, followed by continuous infusion in addition to
      the best medical care. Doses were adjusted in response to anti-factor Xa
      activity. MAIN OUTCOME MEASURES: Favorable outcome rated as the combination of a
      Glasgow Outcome Scale score of I or II and a modified Barthel Index of 12 or
      greater on a scale of 0 to 20 at 3 months or 7 days; very favorable outcome was
      recorded for the combination of a Glasgow Outcome Scale of I and a Barthel Index
      of 19 or 20 at 3 months or 7 days. RESULTS: At 3 months, 482 (75.2%) of 641
      persons assigned to treatment with ORG 10172 and 467 (73.7%) of 634 patients
      treated with placebo had favorable outcomes (P=.49); 49.5% and 47%, respectively,
      of patients in each group had very favorable outcomes at 3 months. At 7 days, 376
      (59.2%) of 635 persons given ORG 10172 and 344 (54.3%) of 633 receiving placebo
      had favorable outcomes (P=.07). For the same interval, 215 (33.9%) of 635 persons
      given ORG 10172 and 176 (27.8%) of 633 persons administered placebo had very
      favorable outcomes (P=.01; odds ratio, 1.36; 95% confidence interval, 1.06-1.73).
      Within 10 days of onset of treatment, serious intracranial bleeding events
      occurred in 14 patients given ORG 10172 (15 events) and in 4 placebo-treated
      patients (5 events) (P=.05). CONCLUSION: Despite an apparent positive response to
      treatment at 7 days, emergent administration of the antithrombotic agent, ORG
      10172, is not associated with an improvement in favorable outcome at 3 months.

PMID- 9565007
TI  - Patients with nonvalvular atrial fibrillation at low risk of stroke during
      treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. The
      SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation
      Investigators.
AB  - CONTEXT: Nonvalvular atrial fibrillation (AF) carries an increased risk for
      stroke, but absolute rates of stroke vary widely within the broad spectrum of AF
      patients. OBJECTIVE: To prospectively validate a risk stratification scheme
      identifying patients with AF with low rates of stroke when given aspirin. DESIGN:
      Prospective cohort study with mean duration of follow-up of 2.0 years, conducted
      between 1993 and 1997. SETTING: Outpatient clinics affiliated with academic
      medical centers. PATIENTS: Patients with AF categorized as "low risk" based on
      the absence of 4 prespecified thromboembolic risk factors: recent congestive
      heart failure or left ventricular fractional shortening of 25% or less, previous
      thromboembolism, systolic blood pressure greater than 160 mm Hg, or female sex at
      age older than 75 years. INTERVENTION: All participants given aspirin, 325 mg/d.
      MAIN OUTCOME MEASURES: Ischemic stroke (considered disabling when Rankin score
      was II or worse 1-3 months later) and systemic embolism (primary events).
      RESULTS: Among 892 participants, the mean (SD) age was 67 (10) years, 78% were
      men, and histories of hypertension, diabetes, and ischemic heart disease were
      present in 46%, 13%, and 16%, respectively. The rate of primary events was 2.2%
      per year (95% confidence interval [CI], 1.6%-3.0%), of ischemic stroke was 2.0%
      per year (95% CI, 1.5%-2.8%), and of disabling ischemic strokes was 0.8% per year
      (95% CI, 0.5%-1.3%). Those with a history of hypertension had a higher rate of
      primary events (3.6% per year) than those with no history of hypertension (1.1%
      per year) (P<.001). The rate of disabling ischemic stroke was low in those with
      and without a history of hypertension (1.4% per year and 0.5% per year,
      respectively). The rate of major bleeding during aspirin therapy was 0.5% per
      year. CONCLUSION: Patients with AF who have relatively low rates of ischemic
      stroke, particularly disabling stroke, during treatment with aspirin can be
      reliably identified.

PMID- 9565008
TI  - Variation in carotid endarterectomy mortality in the Medicare population: trial
      hospitals, volume, and patient characteristics.
AB  - CONTEXT: The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and
      the Asymptomatic Carotid Atherosclerosis Study (ACAS) demonstrated the efficacy
      of carotid endarterectomy (CEA) in reducing the risk of stroke and death in
      selected patients when surgery was performed in institutions whose participation
      depended on demonstrated excellence. Thirty-day mortality rates in the trials
      were very low: 0.6% in NASCET and 0.1% in ACAS. OBJECTIVE: To assess
      perioperative mortality among Medicare patients undergoing CEA in all nonfederal
      institutional settings. DESIGN: Retrospective national cohort study. SETTING AND
      PATIENTS: All 113300 Medicare patients undergoing CEA during 1992 and 1993 in
      "trial hospitals" (those participating in NASCET and ACAS, n=86) and "nontrial
      hospitals" (all other nonfederal institutions performing CEAs, n=2613). Nontrial
      hospitals were stratified into terciles based on volume of CEAs performed. MAIN
      OUTCOME MEASURES: Crude and adjusted perioperative (30 day) mortality rates.
      RESULTS: The perioperative mortality rate was 1.4% (95% confidence interval [CI],
      1.2%-1.7%) at trial hospitals; mortality in nontrial hospitals was higher: 1.7%
      (95% CI, 1.6%-1.8%) (high volume); 1.9% (95% CI, 1.7%-2.1 %) (average volume);
      2.5% (95% CI, 2.0%-2.9%) (low volume); (P for trend, <.001). In multivariate
      modeling, patients undergoing their procedures at trial hospitals had a mortality
      risk reduction of 15% (95% CI, 0%-31%) compared with high-volume nontrial
      hospitals, 25% (95% CI, 7%-40%) compared with average-volume hospitals, and 43%
      (95% CI, 25%-56%) compared with low-volume hospitals (P for trend, <.001).
      CONCLUSION: Medicare patients' perioperative mortality following CEA is
      substantially higher than that reported in the trials, even in those institutions
      that participated in the randomized studies. Caution is advised in translating
      the efficacy of carefully controlled studies of CEA to effectiveness in everyday
      practice.

PMID- 9565009
TI  - Indications, outcomes, and provider volumes for carotid endarterectomy.
AB  - CONTEXT: While trials have demonstrated that carotid endarterectomy is superior
      to best medical therapy, most recently among asymptomatic patients, uses and
      outcomes of the procedure in more representative settings have not been
      established. OBJECTIVES: To profile the use and outcomes of carotid
      endarterectomy in a representative sample of Ohio's Medicare beneficiaries and to
      examine the relationships between provider-specific procedural volumes and
      patient outcomes. DESIGN: Retrospective cohort using Medicare Provider Analysis
      and Review files supplemented by detailed reviews of medical records on a random
      sample of patients. SETTING: Ohio hospitals performing carotid endarterectomy.
      PATIENTS: A random sample of 678 charts of the 4120 non-health maintenance
      organization Medicare beneficiaries who underwent carotid endarterectomy between
      July 1, 1993, and June 30, 1994. MAIN OUTCOME MEASURES: Nonfatal stroke or death
      within 30 days of surgery. RESULTS: The reviewed patients were similar to all
      eligible patients in sociodemographic characteristics and 30-day mortality rates.
      Among the 678 patients, indications for surgery were asymptomatic carotid
      stenosis in 167 (24.6%), transient ischemic attack in 294 (43.4%), completed
      stroke in 62 (9.1%), and nonspecific symptoms in 155 (22.9%). Thirty-two patients
      (4.7%) died or suffered nonfatal strokes by 30 days postoperatively. In
      univariate analyses, rates varied by hospital volume (P=.004) but not surgeons'
      volume (P=.47), although power to detect this difference was limited. Patients at
      higher- and lower-volume hospitals had similar indications and distributions of
      comorbidities. In analyses controlling for indications, comorbid conditions, and
      surgeon's volume, being operated on in a higher-volume hospital conferred a 71%
      reduction in risk for 30-day stroke or death (odds ratio, 0.29; 95% confidence
      interval, 0.12-0.69; P=.006). CONCLUSIONS: Almost half (47.5%) of the carotid
      endarterectomies among Ohio's Medicare population are performed on persons who
      are asymptomatic or who have nonspecific symptoms. These results highlight the
      importance of identifying patients and providers having the most favorable
      outcome profiles. The higher rate of adverse outcomes observed in lower-volume
      hospitals deserves further investigation, as it does not appear to be due to
      differences in patient selection.

PMID- 9565010
TI  - Public perception of stroke warning signs and knowledge of potential risk
      factors.
AB  - CONTEXT: Decreasing the time from stroke onset to hospital arrival and improving
      control of stroke risk factors depend on public knowledge of stroke warning signs
      and risk factors. OBJECTIVE: To assess current public knowledge of stroke warning
      signs and risk factors. DESIGN: A population-based telephone interview survey
      using random digit dialing conducted in 1995. SETTING: The Greater Cincinnati,
      Ohio, metropolitan area, the population of which is similar to that of the United
      States overall in age, sex, percentage of blacks, and economic status.
      PARTICIPANTS: Respondents with age, race, and sex that matched the population of
      patients with acute stroke. MAIN OUTCOME MEASURES: Knowledge of risk factors for
      stroke and warning signs of stroke as defined by the National Institute of
      Neurological Disorders and Stroke. RESULTS: Telephone calls were made to 17634
      households, which yielded 2642 demographically eligible individuals. Interviews
      were completed by 1880 respondents (response rate, 71.2%). A total of 1066
      respondents (57%) correctly listed at least 1 of the 5 established stroke warning
      signs, and of all respondents, 1274 (68%) correctly listed at least 1 of the
      established stroke risk factors. Of the respondents, 469 (57%) of 818 respondents
      with a history of hypertension listed hypertension, 142 (35%) of 402 respondents
      who were current smokers listed smoking, and 32 (13%) of 255 respondents with
      diabetes listed diabetes as a risk factor for stroke. Compared with those younger
      than 75 years, respondents 75 years or older were less likely to correctly list
      at least 1 stroke warning sign (60% vs 47%, respectively; P<.001) and were less
      likely to list at least 1 stroke risk factor (72% vs 56%, respectively; P<.001).
      CONCLUSION: Considerable education is needed to increase the public's awareness
      of the warning signs and risk factors for stroke. Respondents with self-reported
      risk factors for stroke are largely unaware of their increased risk. The
      population at greatest risk for stroke, the very elderly, are the least
      knowledgeable about stroke warning signs and risk factors.

PMID- 9565011
TI  - Cranial computed tomography interpretation in acute stroke: physician accuracy in
      determining eligibility for thrombolytic therapy.
AB  - CONTEXT: Intracranial hemorrhage must be excluded prior to administration of
      thrombolytic agents in acute stroke. OBJECTIVE: To evaluate physician accuracy in
      cranial computed tomography scan interpretation for determining eligibility for
      thrombolytic therapy in acute stroke. DESIGN: Administration of randomly
      selected, randomly ordered series of 15 computed tomography scans from a pool of
      54 scans that demonstrated intracerebral hemorrhage, acute infarction,
      intracerebral calcifications (impostor for hemorrhage), old cerebral infarction
      (impostor for acute infarction), and normal findings. PARTICIPANTS: A convenience
      sample of 38 emergency physicians, 29 neurologists, and 36 general radiologists.
      MAIN OUTCOME MEASURES: Physician determination of eligibility for thrombolytic
      therapy based on computed tomography scan interpretation. RESULTS: Average
      correct score by all physicians on all computed tomography scans was 77% (95%
      confidence interval, 74%-80%). Of 569 computed tomography readings by emergency
      physicians, 67% were correct; of 435 readings by neurologists, 83% were correct;
      and of 540 readings by radiologists, 83% were correct. Overall sensitivity for
      detecting hemorrhage was 82% (95% confidence interval, 78%-85%); 17% of emergency
      physicians, 40% of neurologists, and 52% of radiologists achieved 100%
      sensitivity for identification of hemorrhage. CONCLUSION: Physicians in this
      study did not uniformly achieve a level of sensitivity for identification of
      intracerebral hemorrhage sufficient to permit safe selection of candidates for
      thrombolytic therapy.

PMID- 9565012
TI  - Further evolution toward effective therapy for acute ischemic stroke.
AB  - The effective treatment of acute ischemic stroke remains an important goal of
      modern medicine and substantive advances are occurring. Recently, thrombolytic
      therapy with tissue-type plasminogen activator was approved for selected patients
      with acute ischemic stroke when therapy is started within 3 hours of onset.
      Streptokinase therapy for acute ischemic stroke has not been shown to be
      effective and is associated with an increased risk of hemorrhage, although it was
      not evaluated as early after stroke onset as tissue-type plasminogen activator.
      Various types of neuroprotective interventions are effective in animal models,
      but none has yet been proven effective in patients. In the future, combinations
      of thrombolytic and neuroprotective drugs may be used to attempt maximum rates of
      recovery after acute ischemic stroke. For combination therapy to achieve its
      maximum potential, patients with acute ischemic stroke will have to be carefully
      selected and treated.

PMID- 9565013
TI  - Stroke treatment: promising but still struggling.

PMID- 9565014
TI  - Timely and appropriate treatment of acute stroke: what's missing from this
      picture?

PMID- 9565016
TI  - Migraine relief with acetaminophen, aspirin, and caffeine: abstract and
      commentary.

PMID- 9565018
TI  - Curbs on research dropped from US medical privacy bill.

PMID- 9565019
TI  - Call to boost research on particulates.

PMID- 9565020
TI  - US and Japanese scientists in dispute over 'poisoned' radishes.

PMID- 9565021
TI  - Problems of germline therapy.

PMID- 9565022
TI  - Problems of germline therapy.

PMID- 9565024
TI  - Speculation is premature.

PMID- 9565023
TI  - No viral disease after xenotransplantation.

PMID- 9565025
TI  - In victu veritas.

PMID- 9565026
TI  - Developmental biology. Pulling the fly's leg.

PMID- 9565027
TI  - Code for collagen's stability deciphered.

PMID- 9565028
TI  - Gene translocation links insects and crustaceans.

PMID- 9565029
TI  - Electron transfer by domain movement in cytochrome bc1.
AB  - The cytochrome bc1 is one of the three major respiratory enzyme complexes
      residing in the inner mitochondrial membrane. Cytochrome bc1 transfers electrons
      from ubiquinol to cytochrome c and uses the energy thus released to form an
      electrochemical gradient across the inner membrane. Our X-ray crystal structures
      of the complex from chicken, cow and rabbit in both the presence and absence of
      inhibitors of quinone oxidation, reveal two different locations for the extrinsic
      domain of one component of the enzyme, an iron-sulphur protein. One location is
      close enough to the supposed quinol oxidation site to allow reduction of the Fe-S
      protein by ubiquinol. The other site is close enough to cytochrome c1 to allow
      oxidation of the Fe-S protein by the cytochrome. As neither location will allow
      both reactions to proceed at a suitable rate, the reaction mechanism must involve
      movement of the extrinsic domain of the Fe-S component in order to shuttle
      electrons from ubiquinol to cytochrome c1. Such a mechanism has not previously
      been observed in redox protein complexes.

PMID- 9565030
TI  - Surface topography dependence of biomolecular hydrophobic hydration.
AB  - Many biomolecules are characterized by surfaces containing extended nonpolar
      regions, and the aggregation and subsequent removal of such surfaces from water
      is believed to play a critical role in the biomolecular assembly in cells. A
      better understanding of the hydrophobic hydration of biomolecules may therefore
      yield new insights into intracellular assembly. Conventional views hold that the
      hydration shell of small hydrophobic solutes is clathrate-like, characterized by
      local cage-like hydrogen-bonding structures and a distinct loss in entropy. The
      hydration of extended nonpolar planar surfaces, however, appears to involve
      structures that are orientationally inverted relative to clathrate-like hydration
      shells, with unsatisfied hydrogen bonds that are directed towards the hydrophobic
      surface. Here we present computer simulations of the interaction between the
      polypeptide melittin and water that demonstrate that the two different hydration
      structures also exist near a biomolecular surface. We find that the two
      structures are distinguished by a substantial difference in the water-water
      interaction enthalpy, and that their relative contributions depend strongly on
      the surface topography of the melittin molecule: clathrate-like structures
      dominate near convex surface patches, whereas the hydration shell near flat
      surfaces fluctuates between clathrate-like and less-ordered or inverted
      structures. The strong influence of surface topography on the structure and free
      energy of hydrophobic hydration is likely to hold in general, and will be
      particularly important for the many biomolecules whose surfaces contain convex
      patches, deep or shallow concave grooves and roughly planar areas.

PMID- 9565031
TI  - Encoding of three-dimensional structure-from-motion by primate area MT neurons.
AB  - We see the world as three-dimensional, but because the retinal image is flat, we
      must derive the third dimension, depth, from two-dimensional cues. Image movement
      provides one of the most potent cues for depth. For example, the shadow of a
      contorted wire appears flat when the wire is stationary, but rotating the wire
      causes motion in the shadow, which suddenly appears three-dimensional. The neural
      mechanism of this effect, known as 'structure-from-motion', has not been
      discovered. Here we study cortical area MT, a primate region that is involved in
      visual motion perception. Two rhesus monkeys were trained to fixate their gaze
      while viewing two-dimensional projections of transparent, revolving cylinders.
      These stimuli appear to be three-dimensional, but the surface order perceived
      (front as opposed to back) tends to reverse spontaneously. These reversals occur
      because the stimulus does not specify which surface is in front or at the back.
      Monkeys reported which surface order they perceived after viewing the stimulus.
      In many of the neurons tested, there was a reproducible change in activity that
      coincided with reversals of the perceived surface order, even though the stimulus
      remained identical. This suggests that area MT has a basic role in structure-from
      motion perception.

PMID- 9565032
TI  - Glycine-receptor activation is required for receptor clustering in spinal
      neurons.
AB  - The ability of nerve cells to receive up to several thousands of synaptic inputs
      from other neurons provides the anatomical basis for information processing in
      the vertebrate brain. The formation of functional synapses involves selective
      clustering of neurotransmitter receptors at presumptive postsynaptic regions of
      the neuronal plasma membrane. Receptor-associated proteins are believed to be
      crucial for this process. In spinal neurons, synaptic targeting of the inhibitory
      glycine receptor (GlyR) depends on the expression of the anchoring protein
      gephyrin. Here we show that the competitive GlyR antagonist strychnine and L-type
      Ca2+-channel blockers inhibit the accumulation of GlyR and gephyrin at
      postsynaptic membrane areas in cultured rat spinal neurons. Our data are
      consistent with a model in which GlyR activation that results in Ca2+ influx is
      required for the clustering of gephyrin and GlyR at developing postsynaptic
      sites. Similar activity-driven mechanisms may be of general importance in
      synaptogenesis.

PMID- 9565033
TI  - Cryptochrome blue-light photoreceptors of Arabidopsis implicated in phototropism.
AB  - Phototropism-bending towards the light-is one of the best known plant tropic
      responses. Despite being reported by Darwin and others over a century ago to be
      specifically under the control of blue light, the photoreceptors mediating
      phototropism have remained unknown. We have characterized a blue-light
      photoreceptor from Arabidopsis, named CRY1 for cryptochrome 1; this photoreceptor
      is a flavoprotein that mediates numerous blue-light-dependent responses. In
      Arabidopsis, HY4 (the gene encoding CRY1) is a member of a small gene family that
      also encodes a related photoreceptor, CRY2, which shares considerable functional
      overlap with CRY1. Here we report that mutant plants lacking both the CRY1 and
      the CRY2 blue-light photoreceptors are deficient in the phototropic response.
      Transgenic Arabidopsis plants overexpressing CRY1 or CRY2 show enhanced
      phototropic curvature. We conclude that cryptochrome is one of the photoreceptors
      mediating phototropism in plants.

PMID- 9565034
TI  - Control of antennal versus leg development in Drosophila.
AB  - During the evolution of insects from a millipede-like ancestor, the Hox genes are
      thought to have promoted the diversification of originally identical body
      structures. In Drosophila melanogaster, antennae and legs are homologous
      structures that differ from each other as a result of the Hox gene Antennapedia
      (Antp), which promotes leg identities by repressing unknown antennal-determining
      genes. Here we present four lines of evidence that identify extradenticle (exd)
      and homothorax (hth) as antennal-determining genes. First, removing the function
      of exd or hth, which is required for the nuclear localization of Exd protein,
      transforms the antenna into leg; such transformations occur without activation of
      Antp. Second, hth is expressed and Exd is nuclear in most antennal cells, whereas
      both are restricted to proximal cells of the leg. Third, Antp is a repressor of
      hth. Fourth, ectopic expression of Meis1, a murine hth homologue, can trigger
      antennal development elsewhere in the fly. Taken together, these data indicate
      that hth is an antennal selector gene, and that Antp promotes leg development by
      repressing hth and consequently nuclear Exd.

PMID- 9565035
TI  - Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells.
AB  - DNA viruses have evolved elaborate mechanisms to overcome host antiviral
      defences. In adenovirus-infected cells, programmed cell death (apoptosis) induced
      by the cytokine tumour necrosis factor (TNF) is inhibited by several adenovirus
      encoded proteins. Occupation of the cell-surface receptor Fas, a member of the
      TNF-receptor superfamily that is expressed on most cell types, triggers apoptosis
      of that cell. Here we show that the adenovirus RID (for receptor internalization
      and degradation) protein complex, which is an inhibitor of TNF-induced apoptosis,
      mediates internalization of cell-surface Fas and its destruction inside lysosomes
      within the cell. Fas has not previously been shown to be internalized and then
      degraded. RID also mediates internalization of the receptor for epidermal growth
      factor, but it does not affect the transferrin receptor or class I antigens of
      the major histocompatibility complex. Removal of Fas from the surface of
      adenovirus-infected cells expressing RID may allow infected cells to resist Fas
      mediated cell death and thus promote their survival.

PMID- 9565036
TI  - Integrin binding and mechanical tension induce movement of mRNA and ribosomes to
      focal adhesions.
AB  - The extracellular matrix (ECM) activates signalling pathways that control cell
      behaviour by binding to cell-surface integrin receptors and inducing the
      formation of focal adhesion complexes (FACs). In addition to clustered integrins,
      FACs contain proteins that mechanically couple the integrins to the cytoskeleton
      and to immobilized signal-transducing molecules. Cell adhesion to the ECM also
      induces a rapid increase in the translation of preexisting messenger RNAs. Gene
      expression can be controlled locally by targeting mRNAs to specialized
      cytoskeletal domains. Here we investigate whether cell binding to the ECM
      promotes formation of a cytoskeletal microcompartment specialized for
      translational control at the site of integrin binding. High-resolution in situ
      hybridization revealed that mRNA and ribosomes rapidly and specifically localized
      to FACs that form when cells bind to ECM-coated microbeads. Relocation of these
      protein synthesis components to the FAC depended on the ability of integrins to
      mechanically couple the ECM to the contractile cytoskeleton and on associated
      tension-moulding of the actin lattice. Our results suggest a new type of gene
      regulation by integrins and by mechanical stress which may involve translation of
      mRNAs into proteins near the sites of signal reception.

PMID- 9565037
TI  - Electron currents generated by the human phagocyte NADPH oxidase.
AB  - Electron transport across biological membranes is a well-known feature of
      bacteria, mitochondria and chloroplasts, where it provides motive forces for
      vectorial transport processes. In contrast, electron transport is generally not
      found in the plasma membrane of eukaryotic cells, possibly because it would
      interfere with electric processes at the plasma membrane. An exception is
      provided by the phagocyte NADPH oxidase, which generates superoxide (O2.-)
      through electron transfer from cytosolic NADPH to extracellular oxygen. The
      enzyme is essential for host defence, and patients with chronic granulomatous
      disease, who lack the functional enzyme, suffer from severe infections. It has
      been suggested that electron transfer by the NADPH oxidase might be electrogenic.
      Here we demonstrate, using the whole-cell patch-clamp technique, the generation
      of electron currents by the NADPH oxidase in human eosinophil granulocytes. The
      currents were absent in granulocytes of sufferers of chronic granulomatous
      disease and under conditions of low oxygen. Generation of electron currents
      across the plasma membrane of eukaryotic cells has not been observed previously
      and might be-independently of the generation of superoxide-a physiologically
      relevant function of the phagocyte NADPH oxidase.

PMID- 9565038
TI  - Hyperopic automated lamellar keratoplasty: complications and visual results.
AB  - OBJECTIVE: To examine the long-term safety and efficacy of hyperopic automated
      lamellar keratoplasty (H-ALK) for correction of primary hyperopia and for
      consecutive hyperopia following overcorrected myopic refractive surgery. METHODS:
      A prospective study was done on 67 eyes of 50 consecutive patients who underwent
      H-ALK between March 17, 1993, and August 18, 1995. Hyperopic automated lamellar
      keratoplasty was performed for primary hyperopia in 25 eyes (group 1) and for
      consecutive hyperopia after myopic refractive surgery in 42 eyes (group 2, radial
      keratotomy, 41 eyes, and myopic automated lamellar keratoplasty, 1 eye). The eyes
      were followed up for a mean+/-SD of 19.2+/-12.8 months (range, 3-49 months), 58
      (87%) of them with 6 months' follow-up, and 45 (67%) of them with at least 1
      year's follow-up. Twenty-one eyes were followed up for 2 to 4 years. RESULTS: The
      overall mean+/-SD preoperative spherical equivalent was +2.87+/-1.28 diopters
      (D). The mean+/-SD postoperative spherical equivalent was -0.03+/-1.42 D at 3
      months, -0.42+/-2.25 D at 6 months, -0.55+/-3.00 D at 1 year, -1.58+/-1.53 D at 2
      years, and -0.35+/-1.79 D at the last follow-up. A mean myopic shift of 0.50 D
      was noted between 3 months and 1 year, and of 1.00 D between 1 and 2 years.
      Hyperopia was meaningfully reduced and visual acuity was improved by H-ALK,
      especially for patients with primary hyperopia. Long-term refractive instability,
      however, is a serious problem with this procedure. In this series, 11 (26%) of 42
      eyes in which H-ALK was performed for consecutive hyperopia developed iatrogenic
      keratoconus. CONCLUSION: Based on this study, the long-term instability of H-ALK
      and the high incidence of iatrogenic keratoconus following the procedure should
      discourage its use, especially for consecutive hyperopia following radial
      keratotomy.

PMID- 9565039
TI  - Amniotic membrane transplantation with or without limbal allografts for corneal
      surface reconstruction in patients with limbal stem cell deficiency.
AB  - OBJECTIVE: To examine whether amniotic membrane transplantation (AMT), in
      preparing the perilimbal stroma, enhances the success of allograft limbal
      transplantation (ALT). METHODS: Thirty-one eyes of 26 consecutive patients had
      cytologically proven limbal deficiency resulting from chemical burns (14 eyes);
      Stevens-Johnson syndrome, toxic epidermal necrolysis, or pseudopemphigoid (5
      eyes); contact lens-induced keratopathy (3 eyes); aniridia (3 eyes); multiple
      surgical procedures (2 eyes); atopy (2 eyes); or an unknown cause (2 eyes). Based
      on the severity of limbal deficiency, group A (mild), comprising 10 eyes,
      received AMT alone; group B (moderate), comprising 7 eyes, received AMT and ALT;
      and group C (severe), comprising 14 eyes, received AMT, ALT, and penetrating
      keratoplasty. All patients except those in group A received continuous oral
      cyclosporine. RESULTS: Except for the 2 eyes with atopy, all amniotic membrane
      covered surfaces showed rapid epithelialization (in 2 to 4 weeks) and reduced
      inflammation, vascularization, and scarring, and the surfaces became smooth and
      wettable. For the mean follow-up period of 15.4 months, 25 (83%) of 30 eyes
      showed visual improvement, consisting of 6 or more lines (13 eyes), 4 to 5 lines
      (6 eyes), or 1 to 3 lines (6 eyes). Visual improvement decreased with the
      severity of limbal deficiency from 8 (100%) of 8 eyes in group A to 5 (71%) of 7
      eyes in group B and 11 (79%) of 14 eyes in group C. In group C, corneal graft
      rejection occurred in 9 (64%) of 14 eyes, and reversible early limbal allograft
      rejection was noted in 3 (14%) of 21 eyes of groups B and C. CONCLUSIONS: For
      partial limbal deficiency with superficial involvement, AMT alone is sufficient
      and hence superior to ALT because there is no need to administer cyclosporine.
      For total limbal deficiency, additional ALT is needed, and AMT helps reconstruct
      the perilimbal stroma, with reduced inflammation and vascularization, which
      collectively may enhance the success of ALT.

PMID- 9565040
TI  - Late-onset bleb leaks after glaucoma filtering surgery.
AB  - OBJECTIVE: To determine the incidence of focal, late-onset, conjunctival bleb
      leaks after glaucoma filtering surgery. DESIGN: Prospective, cross-sectional
      analysis. SETTING: Tertiary care outpatient referral center. PATIENTS:
      Consecutive patients who underwent glaucoma filtering surgery prior to June 1996
      presenting for evaluation from September 2,1996, through November 15,1996. Five
      hundred twenty-five eyes of 525 consecutive patients were enrolled in the study.
      INTERVENTION: Bleb height (elevated or flat), area (diffuse or localized), and
      wall thickness (thin, thick, or encapsulated) were classified. Each bleb was
      tested for focal leakage using a moistened fluorescein strip, cobalt blue
      illumination, and slit-lamp biomicroscopy. Diffuse transconjunctival aqueous flow
      did not qualify as a focal leak. MAIN OUTCOME MEASURE: Seidel-positive aqueous
      leakage. RESULTS: Bleb leakage occurred in 14 eyes following trabeculectomy
      (mitomycin C treatment, 10 eyes; 5-fluorouracil treatment, 3 eyes; no
      antifibrosis agent, 1 eye) and in 1 eye following combined cataract and glaucoma
      surgery with adjunctive mitomycin C therapy. Bleb leakage occurred more
      frequently in eyes that received mitomycin C (10 [3.7%] of 273 eyes) than 5
      fluorouracil (3 [1.4%] of 213 eyes) or no antifibrosis agent (1 [2.6%] of 39
      eyes), using Kaplan-Meier estimates (P=.008, log-rank test). Conjunctival blebs
      were significantly thinner after trabeculectomy with mitomycin C than with 5
      fluorouracil (P=.001). Bleb wall thickness was greater following combined
      cataract and glaucoma surgery than following trabeculectomy alone (P=.008). Age
      (P=.84), sex (P=.68), race (P=.77), duration of mitomycin C exposure (P=.62),
      number of antiglaucoma medications (P=.16), and total 5-fluorouracil dose (P=.85)
      were not associated with late-onset leaks. CONCLUSIONS: The risk of late-onset
      focal bleb leakage increases following trabeculectomy with mitomycin C therapy.
      Late leakage after combined cataract and glaucoma surgery is infrequent.

PMID- 9565041
TI  - Cataract surgery and intraocular lens implantation in patients with
      retinoblastoma.
AB  - OBJECTIVE: To report the visual outcome and complications after extracapsular
      cataract extraction with posterior chamber intraocular lens (IOL) implantation in
      eyes that underwent external beam radiotherapy for the treatment of
      retinoblastoma. METHODS: Eleven eyes of 8 patients aged 1.5 to 8.0 years at the
      time of surgery for irradiation-induced cataract were observed for 6 to 39 months
      (mean [+/-SD], 20+/-10 months). A standard technique of extracapsular cataract
      extraction, posterior chamber IOL implantation, pars plana posterior capsulotomy,
      and pars plana anterior vitrectomy was performed in 9 eyes, and secondary IOL
      placement was performed in 2 eyes. RESULTS: All eyes that underwent primary IOL
      implantation achieved visual acuities equal to or better than those best ever
      recorded prior to the development of the cataract. There were no postoperative
      complications, and all eyes experienced minimal postoperative inflammation. The 2
      eyes that underwent secondary IOL implantation achieved their best-corrected
      aphakic visual acuities but experienced a prolonged course of postoperative
      inflammation. CONCLUSION: Intraocular lens placement in the posterior chamber of
      eyes with regressed retinoblastoma and irradiation-induced cataract seems to be a
      safe and effective method for the correction of aphakia.

PMID- 9565042
TI  - Simultaneous indocyanine green and fluorescein angiography using a confocal
      scanning laser ophthalmoscope.
AB  - BACKGROUND: Fluorescein and indocyanine green (ICG) angiography are both useful
      in the diagnosis and treatment of many retinal diseases. In some cases, both
      tests must be performed for diagnosis and treatment; however, performing both is
      time-consuming and may require multiple injections. METHODS: We designed a
      compact digital confocal scanning laser ophthalmoscope to perform true
      simultaneous fluorescein and ICG angiography. We report our experience using the
      instrument to perform 169 angiograms in 117 patients. RESULTS: There were no
      unexpected adverse effects from mixing the dyes and administering them in 1
      injection. An entire examination, including fundus photography, fluorescein
      angiography, and ICG angiography, could be performed in 45 minutes. It was
      possible to study differences in fluorescein patterns by comparing identically
      timed frames and to find cases in which ICG or fluorescein was optimal in
      visualizing retinal and subretinal structures. Confocal optical sections in the
      depth (z) dimension allowed viewing in different planes. It was possible to
      overlay ICG and fluorescein images or compare them side-by-side using a linked
      cursor. Digital transmission of the images was also performed. CONCLUSIONS:
      Simultaneous ICG and fluorescein angiography can be performed rapidly, safely,
      and conveniently. The availability of simultaneous angiography will allow
      critical determination of the relative advantages and disadvantages of both types
      of angiography.

PMID- 9565043
TI  - Spontaneous resolution of retinal detachment occurring after macular hole
      surgery.
AB  - OBJECTIVE: To document the spontaneous resolution of retinal detachment
      developing after macular hole surgery. METHODS: We identified all patients who
      developed a postoperative retinal detachment after undergoing macular hole
      surgery at Washington University School of Medicine, St Louis, Mo; the surgery
      was performed by one of us (L.V.D.P. or H.J.K.) between 1991 and 1996. RESULTS:
      Six of 73 eyes developed a postoperative retinal detachment; the retinal
      detachment was inferior in all cases. Two eyes that had inferior retinal breaks
      underwent further surgery to repair the retinal detachment. Retinal breaks could
      not be identified in the other 4 eyes; the retinal detachment resolved without
      further surgery in all 4 of these eyes. CONCLUSION: The recognition that retinal
      detachment occurring after macular hole surgery can resolve without additional
      surgery may result in the avoidance of further surgical intervention in some
      eyes.

PMID- 9565044
TI  - Reactivation of inflammatory lesions in ocular histoplasmosis.
AB  - BACKGROUND: Active inflammation has not been traditionally associated with the
      ocular histoplasmosis syndrome. OBJECTIVE: To investigate the occurrence of
      presumed inflammatory chorioretinal lesions in patients with the ocular
      histoplasmosis syndrome. METHODS: Patients seen with acute symptoms and a
      clinical picture of ocular histoplasmosis were observed prospectively between
      August 13, 1993, and December 2, 1997. Symptoms, visual acuity, and fluorescein
      sodium angiography were used to document changes in inflammatory loci. RESULTS:
      Twelve patients were seen with active inflammatory lesions. Eleven had resolution
      of the loci with lessening of symptoms and improvement in acuity and angiographic
      findings. A typical subretinal neovascular membrane developed in 1 patient 8
      months after the onset of symptoms. CONCLUSIONS: Inflammatory chorioretinal
      lesions can reactivate in the ocular histoplasmosis syndrome. In most of these
      patients, neovascularization did not develop and visual acuity was preserved.

PMID- 9565045
TI  - Distance/near differences in intermittent exotropia.
AB  - BACKGROUND: Burian's classification of exotropia based on the difference between
      the distance deviation and near deviation (distance/near differences) leaves some
      questions unanswered. Controversy exists concerning whether the divergence excess
      pattern is caused by an excess of divergence or by excessive accommodative
      convergence. Much of the literature on this subject has been confusing because
      investigators did not eliminate tenacious proximal fusion as an artifact in
      calculating the ratio of accommodative convergence to accommodation (AC/A ratio).
      Previously, one of us (B.J.K.) proposed a classification system that respected
      this artifact and subdivided the classification system proposed by Burian.
      METHODS: A total of 202 consecutive patients with an exotropia underwent a series
      of measurements to determine the respective role of accommodative convergence and
      tenacious proximal fusion as a cause for their distance/near differences. In
      addition, the value obtained by a rapid prism adaptation test as a possible
      substitute for 1 hour of monocular occlusion was studied. RESULTS: In 98
      patients, the initial distance deviation exceeded the near deviation. In 10
      patients, the distance/near differences were caused by a high AC/A ratio, which
      would have been mislabeled by Burian's classification system. Brown's
      recommendation of using +3.00-diopter lenses at near to diagnose simulated
      divergence excess would have led to the misdiagnosis of a high AC/A ratio in 61
      of these patients. In 26 patients, the near deviation exceeded the distance
      deviation. Burian's classification would have incorrectly labeled 2 patients as
      having convergence insufficiency when, in fact, they had pseudoconvergence
      insufficiency. The new proposed classification system proved 100% sensitive and
      100% specific (6 of 6 patients for both parameters) for identifying
      preoperatively exotropic patients who postoperatively developed an esotropia at
      near with a high AC/A ratio. Rapid prism adaptation tests at near proved useful
      for identifying the presence of tenacious proximal fusion, but were not accurate
      in its quantification. CONCLUSIONS: The validity and utility of the new
      classification system was confirmed. Identification of exotropic patients with a
      high AC/A ratio and consideration of nonsurgical treatment is important. The
      rapid prism adaptation test is qualitatively, but not quantitatively, the same as
      1 hour of monocular occlusion.

PMID- 9565046
TI  - A look at the past. Jacques Daviel, 1693-1762.

PMID- 9565047
TI  - Laser energy reaching the posterior pole during transscleral
      cyclophotocoagulation.
AB  - OBJECTIVE: To measure scattered laser energy reaching the posterior pole during
      transscleral cyclophotocoagulation. METHODS: Transscleral cyclophotocoagulation
      was performed on 4 cadaver eyes with Nd:YAG noncontact, Nd:YAG contact, and diode
      contact lasers. Energy was measured with a photodiode through a 7-mm trephined
      hole in the posterior pole. Average percentage power, average power, and average
      energy transmission were calculated. American Conference of Governmental
      Industrial Hygienists (ACGIH) guidelines were used to calculate allowable energy
      exposures for each laser. RESULTS: All 3 lasers transmitted 3% to 5% of the power
      to the posterior pole. The average energy transmission was 240 to 260 mJ for all
      lasers. The contact lasers had an average power transmission of 120 mW. The
      noncontact Nd:YAG laser, with shorter pulse duration, had an average power
      transmission of 13,000 mW, significantly greater than that of the other lasers.
      The ACGIH guidelines for allowable energy exposures were 93 mJ for the noncontact
      Nd:YAG laser, 1300 mJ for the contact Nd:YAG laser, and 440 mJ for the contact
      diode laser. CONCLUSIONS: Three percent to 5% of laser power delivered during
      cyclophotocoagulation reaches the posterior pole. Exposure energies may approach
      or exceed ACGIH guidelines. The clinical significance of these findings remains
      to be shown.

PMID- 9565048
TI  - Relationship of optic disc topography to optic nerve fiber number in glaucoma.
AB  - OBJECTIVE: To assess the relationship between in vivo measurements of optic disc
      topography and histomorphometric measurements of optic nerve fiber number in
      glaucoma. METHODS: Both eyes of 10 monkeys (Macaca fascicularis) with laser
      induced glaucoma in the right eye were studied. Optic disc topography was
      measured in vivo with a confocal scanning laser ophthalmoscope. Histomorphometry
      was performed on optic nerve cross sections using bright-field microscopy with
      camera lucida. Nerve fiber density was estimated by unbiased random sampling.
      Nerve fiber number was estimated for each sector by multiplying nerve fiber
      density with neuroglial area. Nerve fiber count was compared with each of 13
      global optic disc topographic parameters. RESULTS: For neuroretinal measurements
      in the glaucomatous eyes, rim area, retinal nerve fiber layer (RNFL) cross
      sectional area, rim volume, and RNFL thickness correlated significantly with
      optic nerve fiber number. Differences in nerve fiber count between control and
      glaucomatous optic nerves showed the strongest correlation with differences in
      mean height contour; this was followed by RNFL cross-sectional area, RNFL
      thickness, rim volume, and differences in rim area. For cup measurements in the
      glaucomatous eyes, cup volume below reference, cup area, mean cup depth, the
      ratio of cup area to disc area, and cup shape correlated significantly with nerve
      fiber number. Differences in nerve fiber number between control and glaucomatous
      optic nerves showed the strongest correlation with differences in cup shape; this
      was followed by mean cup depth, cup volume below reference, the ratio of cup area
      to disc area, cup area, and differences in cup volume below surface. No
      association was found between optic nerve fiber number and optic disc area in
      glaucomatous eyes. CONCLUSIONS: In experimental glaucoma, most optic disc
      topography measures correlated significantly with optic nerve fiber number. The
      results of this histomorphometric study support the use of confocal scanning
      laser ophthalmoscopy to evaluate optic nerve damage in glaucoma.

PMID- 9565049
TI  - Arrestin gene mutations in autosomal recessive retinitis pigmentosa.
AB  - OBJECTIVE: To assess the clinical and molecular genetic studies of patients with
      autosomal recessive retinitis pigmentosa associated with a mutation in the
      arrestin gene. DESIGN: Results of molecular genetic screening and case reports
      with DNA analysis and clinical features. SETTING: University medical center.
      PATIENTS: One hundred twenty anamnestically unrelated patients with autosomal
      recessive retinitis pigmentosa. METHODS: DNA analysis was performed by single
      strand conformation polymorphism followed by nucleotide sequencing to search for
      a mutation in exon 11 of the arrestin gene. Clinical features were characterized
      by visual acuity slitlamp biomicroscopy, fundus examinations, fluorescein
      angiography, kinetic visual field testing, and electroretinography. RESULTS: We
      identified 3 unrelated patients with retinitis pigmentosa associated with a
      homozygous 1-base-pair deletion mutation in codon 309 of the arrestin gene
      designated as 1147delA. All 3 patients showed pigmentary retinal degeneration in
      the midperipheral area with or without macular involvement. Patient 1 had a
      sibling with Oguchi disease associated with the same mutation. Patient 2
      demonstrated pigmentary retinal degeneration associated with a golden-yellow
      reflex in the peripheral fundus. Patients 1 and 3 showed features of retinitis
      pigmentosa without the golden-yellow fundus reflex. CONCLUSIONS: Although the
      arrestin 1147delA has been known as a frequent cause of Oguchi disease, this
      mutation also may be related to the pathogenesis of autosomal recessive retinitis
      pigmentosa. This phenomenon may provide evidence of variable expressivity of the
      mutation in the arrestin gene.

PMID- 9565050
TI  - Critical periods and amblyopia.
AB  - During the past 20 years, basic science has shown that there are different
      critical periods for different visual functions during the development of the
      visual system. Visual functions processed at higher anatomical levels within the
      system have a later critical period than functions processed at lower levels.
      This general principle suggests that treatments for amblyopia should be followed
      in a logical sequence, with treatment for each visual function to be started
      before its critical period is over. However, critical periods for some visual
      functions, such as stereopsis, are not yet fully determined, and the optimal
      treatment is, therefore, unknown. This article summarizes the current extent of
      our knowledge and points to the gaps that need to be filled.

PMID- 9565051
TI  - The relationship of ocular factors to the incidence and progression of age
      related maculopathy.
AB  - OBJECTIVE: To examine the association between ocular factors and the incidence
      and progression of age-related maculopathy. PARTICIPANTS: A population of 3684
      adults (43-86 years of age at baseline) living in Beaver Dam, Wis, studied at
      baseline and 5 years later. METHODS: Standardized protocols for refraction and
      determination of iris color, administration of a questionnaire, and slitlamp and
      retroillumination photographs of the lenses to determine cataract type and
      stereoscopic color fundus photographs to determine presence and severity of age
      related maculopathy. Standard univariate and multivariate analyses were
      performed. MAIN OUTCOME MEASURES: Incidence and progression of age-related
      maculopathy. RESULTS: After controlling for age, eyes that had undergone cataract
      surgery before baseline were more likely to have progression of age-related
      maculopathy (odds ratio, 2.71; 95% confidence interval [CI], 1.69-4.35) and to
      develop signs of late age-related maculopathy (odds ratio, 2.80; 95% CI, 1.03
      7.63) than were eyes that were phakic at baseline. These relationships remained
      after controlling for other risk factors in multivariate analyses. There was no
      relationship of nuclear cataract, cortical cataract, or iris color to the
      incidence and progression of age-related maculopathy. CONCLUSION: These findings
      indicate a relationship between cataract surgery and increased risk of
      progression of age-related maculopathy.

PMID- 9565052
TI  - The psychosocial impact of macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD), the leading cause of
      irreversible blindness and low vision among the elderly, has not been well
      studied with regard to its impact on daily life. This study was designed to
      demonstrate the impact of AMD on quality of life, emotional distress, and
      functional level. PARTICIPANTS: The study sample consisted of 86 elderly adults
      (average age, 79 years) with AMD who were legally blind in at least 1 eye.
      Participants completed a battery of measures that included the Quality of Well
      being Scale, the Instrumental Activities of Daily Living index, self-rated
      general health status, and the Profile of Mood States. RESULTS: Persons with AMD
      experienced significant reductions in key aspects of daily life. Their ratings
      for quality of life (average Quality of Well-being Scale score=0.581) and
      emotional distress (average Profile of Mood States total score=65.36) were
      significantly worse than those for similarly aged community adults and were
      comparable with those reported by people with chronic illnesses (eg, arthritis,
      chronic obstructive pulmonary disease, acquired immunodeficiency syndrome, and
      bone marrow transplants). Patients with AMD were also more likely than a national
      sample of elderly individuals to need help with daily activities. Visual acuity
      was related to ability to carry out daily activities (Instrumental Activities of
      Daily Living, r=0.28, P=.008). Quality of life ratings were significantly related
      to the ability to carry out daily activities (r=-0.38, P=.001), self-rated
      general health status (r=-0.21, P=.05), and emotional distress (Profile of Mood
      States total score, r=-0.25, P=.02). Individuals with a shorter period of
      perceived vision loss were more likely to report high levels of emotional
      distress (r=-0.24, P=.03) than those with a longer period of perceived vision
      loss. Further, those who were blind in 1 eye were even more significantly
      distressed than those who were blind in both eyes. CONCLUSIONS: Elderly persons
      with AMD causing legal blindness in 1 or both eyes have significant emotional
      distress and profoundly reduced quality of life and need help with key daily
      activities.

PMID- 9565054
TI  - Presumed adenocarcinoma of the retinal pigment epithelium in a blind eye with a
      staphyloma.
AB  - The retinal pigment epithelium (RPE) can undergo reactive hyperplasia and
      metaplasia following a variety of ocular insults. However, true neoplasms of the
      RPE are rare. We report a case of a papillary adenocarcinoma of the RPE arising
      in the blind staphylomatous right eye of a 79-year-old woman with a long history
      of bilateral posterior staphylomas who was seen with increasing pain and
      exophthalmos of the right eye. Findings from ultrasonography and computed
      tomography demonstrated linear calcification consistent with osseous metaplasia
      of the RPE. Progression of the exophthalmos and worsening exposure keratitis led
      to enucleation of the eye. Gross pathology showed a 79-mm-long globe.
      Histopathologic findings revealed a largely amelanotic papillary adenocarcinoma
      arising from the RPE. Positive immunoreactivity for cytokeratin supported the
      epithelial origin of the tumor. Adenocarcinoma of the RPE is rare but may develop
      in a blind eye.

PMID- 9565053
TI  - Evaluating new retinal imaging techniques.

PMID- 9565055
TI  - Hepatitis C-associated keratitis.

PMID- 9565056
TI  - Fingernail trauma causing corneal laceration and intraocular cilia.

PMID- 9565057
TI  - Eye-sparing treatment of massive extrascleral extension of choroidal melanoma.

PMID- 9565058
TI  - Staining of the lens capsule for circular continuous capsulorrhexis in eyes with
      white cataract.
AB  - We have developed a technique of staining the anterior capsule with a solution of
      indocyanine green that facilitates performance of the circular continuous
      capsulorrhexis in eyes with a mature cataract. We compared the results of
      phacoemulsification and intraocular lens implantation in 10 eyes with the capsule
      stained with results of 10 eyes having the same procedure with standard circular
      continuous capsulorrhexis. The results of specular microscopy and laser flare
      cell photometry showed no statistically significant differences between the 2
      groups. Although the safety of intraocular indocyanine green dye has not yet been
      definitively established, the findings of this pilot study suggest that it is
      safe and useful in visualizing the anterior capsule of a mature cataract during
      cataract surgery.

PMID- 9565059
TI  - Plaque radiation therapy for recurrent conjunctival pyogenic granuloma.

PMID- 9565060
TI  - Optic nerve avulsion.

PMID- 9565061
TI  - The fundus in severe malaria.

PMID- 9565062
TI  - Retinopathy and tissue hexose in drug-treated animals.

PMID- 9565063
TI  - Corneal pachymetry: a prerequisite for applanation tonometry?

PMID- 9565064
TI  - Optic disc size and iris color.

PMID- 9565065
TI  - Population-based assessment of childhood blindness in southern India.

PMID- 9565066
TI  - Prognostic relevance of C-myc gene expression in giant-cell tumor of bone.
AB  - Giant-cell tumor is a primary bone tumor, of uncertain origin, with the potential
      capacity to metastasize. To study the role of c-myc and c-fos oncogene
      overexpression in the tumorigenesis and metastatic spread of giant-cell tumors,
      32 primary tumors were collected; of these, 19 remained disease-free and 13
      metastasized to the lung. Samples of lung metastasis from these 13 patients were
      also available for study. The expression of c-myc and c-fos mRNA was studied by
      reverse transcription-polymerase chain reaction and by in situ hybridization. The
      expression of protein was studied by Western blot analysis and by
      immunohistochemistry. C-myc mRNA was overexpressed in 12 (38%) of the 32 primary
      tumors. Thirteen primary tumors metastasized to the lung; in nine (69%) of these,
      c-myc mRNA was overexpressed. The c-myc protein was overexpressed in seven (54%)
      of the 13 tumors that metastasized to the lung. C-fos was overexpressed in only
      one lung metastasis. A strong correlation between the overexpression of c-myc,
      and the occurrence of metastases was found: thus, c-myc seems a powerful
      prognosticator in giant-cell tumor. C-myc was overexpressed both in giant cells
      and in mononuclear cells, suggesting that both cell types are involved in the
      progression of this tumor.

PMID- 9565067
TI  - Evidence for the upregulation of osteogenic protein-1 mRNA expression in
      musculoskeletal neoplasms.
AB  - Little is known about bone and cartilage tumors at the molecular level; thus, the
      identification of genes associated with these tumors may be useful as markers and
      therapeutic targets. To address this issue and to test the hypothesis that
      abnormal expression of one or more growth factors in the transforming growth
      factor-beta superfamily is associated with musculoskeletal neoplasia, degenerate
      primers based on the conserved sequences in these genes were made for screening
      tumor samples by reverse transcription-polymerase chain reaction. First, these
      primers were used to obtain a comparative profile between a low-grade
      chondrosarcoma and its dedifferentiated high-grade counterpart in the same
      patient. This experiment identified an amplified DNA product in the high-grade
      sample that was identical to osteogenic protein-1/bone morphogenetic protein-7.
      Osteogenic protein-1 mRNA expression was 17-fold greater in this high-grade
      sample than in the low-grade one. Osteogenic protein-1 was highly expressed
      (three of three) in human osteosarcoma cell lines but was not expressed (zero of
      four) in normal osteoblast samples. Screening for gene expression of osteogenic
      protein-1 in 57 osteosarcomas and chondrosarcomas indicated that 44% (range: 38
      52%) of them were positive for osteogenic protein-1 mRNA. Screening of breast and
      prostate tumors revealed a similar association with osteogenic protein-1 mRNA
      expression.

PMID- 9565068
TI  - Role of glutathione in cisplatin resistance in osteosarcoma cell lines.
AB  - This study was designed to examine whether and how glutathione and catalase
      increase the resistance of osteosarcoma cells to the toxicity of cisplatin. Eight
      osteosarcoma cell lines were exposed to varying concentrations of cisplatin, and
      a [3H]thymidine incorporation study then estimated their drug sensitivity. Cells
      were pretreated with aminotriazole and buthionine sulfoximine to depress catalase
      and glutathione activities and then entered into the same protocol to assess
      their sensitivity to cisplatin. Intracytoplasmic levels of catalase and
      glutathione were measured before and after the treatments. Cisplatin-glutathione
      conjugates were created to examine how glutathione might depress the toxicity of
      cisplatin. Although the cell lines differed in the magnitude of their response to
      cisplatin, there was a statistical correlation between intrinsic glutathione
      content and cisplatin resistance. Pretreatment with aminotriazole reduced
      catalase activity by 84% but did not change the sensitivity to cisplatin.
      Depletion of glutathione activity by 70% increased the sensitivity of the cells
      to the cytotoxicity of cisplatin. In addition, cisplatin was detoxified following
      conjugation with glutathione. The increased sensitization to cisplatin toxicity
      caused by the depletion of glutathione and cisplatin detoxification after the in
      vitro reaction of glutathione to cisplatin indicated that the formation of the
      glutathione-cisplatin conjugate was an important mechanism in the cellular
      resistance to cisplatin. These data also demonstrated that catalase activity did
      not contribute to resistance to cisplatin and suggested that H2O2-induced
      oxidative stress did not significantly contribute to the cytotoxicity of
      cisplatin in osteosarcoma cells.

PMID- 9565069
TI  - Relationships between bone morphology and bone elastic properties can be
      accurately quantified using high-resolution computer reconstructions.
AB  - It would be advantageous if the mechanical properties of trabecular bone could be
      directly inferred from stereomorphometric parameters. For that purpose, apparent
      density and mean intercept length, as measures of bone mass and directionality
      (fabric), are commonly correlated with the elastic characteristics of bone
      samples, as determined in compression tests. However, complete and accurate
      relationships have not yet been established in this way. This may be due not only
      to the occurrence of artifacts in both the stereomorphometric and the mechanical
      assessments but also to an inherent inadequacy of mean intercept length in
      characterizing the full mechanical significance of bone architecture or
      nonhomogeneities in trabecular tissue properties not accounted for in
      stereomorphometry. In this study, we introduce a computer modeling approach
      allowing these biases to be eliminated. With use of high-resolution three
      dimensional computer reconstructions of trabecular bone specimens for
      stereomorphometry and for microstructural finite element models to simulate
      mechanical tests, unbiased comparisons become feasible. The purpose was to
      investigate if accurate and complete relationships can be established in this
      way. Four different fabric measures were considered: mean intercept length and
      three volume-based ones. Compliance matrices were calculated from fabric tensors,
      with use of the mathematical relationship proposed by Cowin for 29 vertebral
      whale-bone specimens. These were correlated with the compliance constants
      determined directly from the microstructural finite element model simulation. The
      nine orthotropic elastic constants of all 29 specimens were well predicted from
      their stereomorphometric fabric and volume fraction values, with correlation
      coefficients ranging from R2adj = 0.9934 to 0.9963. When individual compliance
      components were considered (1/Ei, 1/Gij, or -v[ij]/Ei), correlation coefficients
      ranged from R2adj = 0.924 to 0.982. All four fabric measures performed equally
      well. It is concluded that volume fraction and fabric measures correlate highly
      with the apparent elastic properties of bone samples, provided that anisotropy
      and nonhomogeneity in the elastic properties of the trabecular tissue itself have
      negligible effects on the apparent properties. Whether this is true for bone in
      general remains to be seen, as only a subset was analyzed here. These methods,
      however, can be valuable in similar assessments of other subsets.

PMID- 9565070
TI  - Evaluation of a bone's in vivo 24-hour loading history for physical exercise
      compared with background loading.
AB  - The present study sought to answer two research questions. First, how
      distinctive, as a potential osteogenic stimulus, are short-duration bouts of
      treadmill exercise relative to sedentary background activity? Second, how well
      does daily effective strain stimulus relate the loading history for one such
      exercise program, in comparison with other experimental loading programs, to bone
      formation? In vivo cortical strains were measured in the tibiotarsus of White
      Leghorn chickens at a late stage of skeletal growth (14-34 weeks old) under the
      conditions of a previous investigation of bone formation in response to an
      exercise program (15 min/day, treadmill gait at 60% maximum speed while carrying
      20% body mass) that included sedentary background activity. These strain data
      were compiled into 24-hour loading histories of peak cyclic strain, demonstrating
      that strains were statistically different for exercise and background activities
      (p < 0.0001), with both the magnitude and number of cyclic strain events being
      greater during exercise (generally greater than 500 microstrain, 2,500
      cycles/day) than during background activity (generally less than 500 microstrain,
      mean: 775 cycles/day). Strains during exercise accounted for more than 97% of the
      daily effective strain stimulus for bone adaptation, despite the fact that
      exercise comprised only 1% of the daily period (15 min/day). The levels of the
      daily effective strain stimulus were similar to those calculated for strains
      engendered by artificial loading of functionally isolated avian ulnae, which
      either maintained bone mass or resulted in a 15% increase of cortical cross
      sectional area in both sets of studies. These results indicate that short
      duration bouts of treadmill exercise and sedentary background activity can
      represent distinct osteogenic stimuli for adaptive bone modeling. They also
      provide experimental support for the use of a daily effective strain stimulus to
      quantify skeletal loading histories for differing programs of physical exercise,
      although the relative importance of other mechanical and nonmechanical factors
      requires further investigation.

PMID- 9565071
TI  - Identification of the oim mutation by dye terminator chemistry combined with
      automated direct DNA sequencing.
AB  - The homozygous oim/oim mouse, a model of moderate-to-severe human osteogenesis
      imperfecta, contains a G-nucleotide deletion in the Cola-2 gene (the murine pro
      alpha(I) collagen gene) that results in accumulation of alpha1(I) homotrimer
      collagen. Although these mice have a distinctive phenotype that includes multiple
      fractures and deformities, genotyping is necessary to distinguish them from their
      wildtype (+/+) and heterozygote (oim/+) littermates. In this study, the dye
      primer and dye terminator chemistry methods, in combination with automated direct
      DNA sequencing, were compared for accuracy and ease in genotyping. A total of 82
      mice from 14 litters were bred and genotyped; this resulted in 18 +/+, 35 oim/+,
      and 29 oim/oim mice. The dye primer and dye terminator chemistry methods worked
      equally well for identification of the deletion mutation and thus the genotype of
      all of the mice. However, the dye terminator method was found to be superior on
      the basis of the reduced amount of sample handling and reduced quantity of
      reagent required.

PMID- 9565072
TI  - Mechanical behavior of human morselized cancellous bone in triaxial compression
      testing.
AB  - Despite its widespread use as graft material in orthopaedic surgical procedures,
      morselized cancellous bone has not yet been well characterized from the
      standpoint of its mechanical properties. To accommodate the noncohesive nature of
      this loose particulate form of bone, a triaxial compression test apparatus
      commonly used in engineering soil mechanics was adapted for the testing of fresh
      frozen human morselized cancellous bone specimens. Triaxial compression tests
      were run to 30% axial strain at five different levels of confining pressure
      ranging from 0.276 to 0.552 MPa. The measured axial stress versus axial strain
      behavior was bimodal, characterized initially by relatively stiff linear
      behavior, then by a rapid transition to a much more compliant (but, again,
      approximately linear) domain until test cessation. The apparent axial moduli of
      both response regions were found to be nearly linear functions of the transverse
      confining pressure. As typically prepared surgically, the distribution of
      particle size was found to have approximately 80% of the bone graft, by weight,
      encompassed in particles 0.42-3.2 mm in size. Triaxial tests of samples
      segregated by size showed that particle size had no appreciable effect on
      apparent material properties. The nominal Young's modulus and Poisson's ratio of
      morselized cancellous bone were 100 MPa and 0.2, respectively.

PMID- 9565073
TI  - Skeletal anomalies in the adriamycin-exposed prenatal rat: a model for VATER
      association.
AB  - Vertebral and radial anomalies are prominent features of VATER (vertebral
      defects, anorectal anomaly, tracheoesophageal fistula with esophageal atresia,
      and radial dysplasia) association. It has been shown that exposure of the rat
      fetus to adriamycin produces a spectrum of anomalies, including esophageal
      atresia and other features of VATER association. We aimed to document the
      skeletal defects found in rats exposed to teratogenic doses of adriamycin in
      utero. Vertebral, rib, and limb anomalies were found in 54, 54, and 35% of these
      examined fetuses, respectively. The range of bone lesions seen in this animal
      model was similar to the range of lesions seen in infants born with VATER
      association.

PMID- 9565074
TI  - Microhardness and anisotropy of the vital osseous interface and endosseous
      implant supporting bone.
AB  - Limited information is available on the mechanical properties of the rapidly
      remodeling bone that surrounds endosseous implants. Fifteen implant-bone blocks
      were obtained from the mid-femoral diaphyses of three mature male hounds 12 weeks
      after placement of the implants. To evaluate the microhardness and cortical
      anisotropy of bone, the implants were sectioned along their long axes. In this
      process, the femurs were sectioned transversely. Knoop microhardness measurements
      (HK) were made with a 50 g force on cortical bone and a 25 g force on periosteal
      callus, endocortical callus, and circumferential lamellar bone. The long diagonal
      of the indenter was placed parallel to the implant (in the radial bone
      direction). Measurements were made in cortical bone at 200, 400, 600, 800, 1,000,
      1,500, 2,000, and 2,500 microm from both sides of the implant. To detect cortical
      anisotropy in the radial compared with the tangential direction, a second set of
      indentations was made perpendicular to the first. Microhardness of periosteal
      callus and endocortical callus and anisotropy of circumferential lamellar bone
      near the endocortical surfaces of the femur were also evaluated. Repeated
      measures analysis of variance showed significantly (p < 0.05) lower microhardness
      values (30.6 +/- 0.8 HK [mean +/- SEM]) for cortical bone at 200 microm than at
      any other location (range: 40.3-46.6 HK). Microhardness anisotropy was not
      detected in cortical bone. Furthermore, within 200 microm of the implant surface,
      the Knoop microhardness values were significantly lower for periosteal and
      endocortical calluses than for cortical bone. These data provide information
      about the mechanical properties of bone adjacent to endosseous implants at a
      microstructural level. The results are consistent with the high rate of
      remodeling seen adjacent to endosseous implants at 12 weeks after implantation.

PMID- 9565075
TI  - Biomechanical characterization of osseointegration: an experimental in vivo
      investigation in the beagle dog.
AB  - This study reports the results of torsion tests, pull-out tests, and lateral
      loading tests on osseointegrated commercially pure titanium fixtures. The tests
      were performed in vivo on six beagle dogs. Three fixtures, each with a diameter
      of 3.7 mm, were installed bilaterally in the tibia of each animal. The mean
      maximal pull-out load was 1.55 kN (n = 4), the mean maximal lateral transverse
      load was 0.21 kN (n = 2), the mean maximal lateral axial load was 0.18 kN (n =
      2), the mean breakpoint torque was 0.31 Nm (n = 3), and the mean maximal torque
      was 0.43 Nm (n = 3). The torsion test revealed an almost immediate plastic
      deformation of the interface between the implant and bone; this indicates that
      although the contact between the bone and the implant is close, there is no
      strong bond, at least not in shear. The major transfer of load from the implant
      to the surrounding bone tissue must therefore depend on the design of the
      implant. A histological evaluation with measurements of the amount of bone in
      contact with the fixtures was performed. By the use of the histological and
      mechanical data, it is possible to estimate shear stresses in bone tissue (pull
      out test) and in the interface (torque test). The mean maximal shear stress in
      bone tissue in the pull-out tests was 100 MPa (n = 4); the mean shear stress in
      the interface was 4.3 MPa (n = 3) in the torsion tests at the breakpoint torque
      and was 6.0 MPa (n = 3) at the maximal torque. It was also possible to estimate
      the shear modulus of elasticity in the pull-out and torque tests. The mean shear
      modulus in pull-out was 119 MPa (n = 4), and the mean apparent shear modulus in
      torsion was 9 kPa (n = 3) for an assumed interface thickness of 100 nm and was 86
      kPa (n = 3) for an assumed interface thickness of 1,000 nm.

PMID- 9565076
TI  - Dye incorporation to enhance the laser ablation of standard and reduced-modulus
      bone cements.
AB  - Laser ablation of acrylic bone cement is an alternative method of cement removal
      that can be used during revision arthroplasty of cemented implants. This study
      investigated the feasibility of using a continuous-wave Argon ion laser
      (wavelength = 514 nm) with the addition of methylene blue or red dye no. 13 to
      enhance the ablation of two types of bone cements: polymethylmethacrylate and
      polybutylmethylmethacrylate. Six cement/dye combinations were studied while power
      (0.5, 0.75, and 1.0 W) and exposure times (30, 45, 60, and 90 seconds) were
      varied. The Argon laser was unable to ablate undyed polymethylmethacrylate or
      polybutylmethylmethacrylate. However, ablation was shown for both cements with
      either dye. The red dye had a stronger absorption peak at 514 nm than did the
      blue dye. Statistically larger ablation areas were seen for red
      polymethylmethacrylate than for blue polymethylmethacrylate (p < 0.013) at all
      levels tested. Ablation areas were larger in red than in blue
      polybutylmethylmethacrylate cement. Blue polybutylmethylmethacrylate cement
      produced larger ablation areas than did blue polymethylmethacrylate cements at
      all energy levels tested, with smaller surrounding damage areas. Red
      polybutylmethylmethacrylate cement also produced larger ablation areas than did
      red polymethylmethacrylate cement (at 0.75 and 1.0 W), again with smaller damage
      areas. Damage zones were smallest in red polybutylmethylmethacrylate cements at
      all test levels. These results suggest that, by using dyes to selectively alter
      the absorption characteristics of bone cement, laser ablation can be an effective
      method for cement removal. Changes in the chemical structure of the cement can
      also influence the response to laser treatment. Furthermore, the absorption
      spectra of the bone cement can be altered to maximize energy absorption at a
      wavelength that is not absorbed by bone tissue; this potentially minimizes damage
      to bone during revision surgery.

PMID- 9565077
TI  - Use of a bioabsorbable polymer for the delivery of ofloxacin during experimental
      osteomyelitis treatment.
AB  - This study was performed to investigate the potential utility of ofloxacin
      impregnated bioabsorbable polymers for osteomyelitis therapy. Pseudomonas
      aeruginosa osteomyelitis was induced in 48 New Zealand White rabbits. Four weeks
      after infection, the animals were randomized to one of four treatment groups:
      drug-free polymer, ofloxacin polymer, systemic ofloxacin, or ofloxacin polymer
      plus systemic ofloxacin. Twenty-eight days later, radiographs were taken of the
      affected area, the animals were killed, and bone was obtained for histologic
      evaluation, culture, and determination of ofloxacin concentrations. The
      percentage of sterile bone cultures was 33, 83, 75, and 91 for the groups treated
      with drug-free polymer, ofloxacin polymer, systemic ofloxacin, and ofloxacin
      polymer plus systemic ofloxacin, respectively. When compared with the drug-free
      polymer, both the ofloxacin polymer and the ofloxacin polymer plus systemic
      ofloxacin significantly improved the rate of sterilization. The mean
      concentrations of the drug in bone for the groups treated with ofloxacin polymer,
      systemic ofloxacin, and ofloxacin polymer plus systemic ofloxacin were 34.9
      (range: 2-160), 1.9 (range: 0.8-3), and 26.0 microg/g (range: 9-100 microg/g),
      respectively. These data suggest that the DL-lactide:glycolide polymer studied is
      a suitable vehicle for the delivery of high local concentrations of ofloxacin and
      that these concentrations result in eradication of the bacterial pathogen in this
      rabbit model.

PMID- 9565078
TI  - Bonding of cartilage matrices with cultured chondrocytes: an experimental model.
AB  - The capacity of isolated chondrocytes to join separate masses of cartilage matrix
      was investigated with composites implanted in subcutaneous pouches in nude mice.
      Slices of articular cartilage were harvested from lambs and were devitalized by
      cyclic freezing and thawing. The slices were then either co-cultured with viable
      allogeneic lamb chondrocytes (experimental) or cultured without such chondrocytes
      (control). Composites of three slices were constructed with use of fibrin glue
      and were implanted in nude mice for periods ranging from 7 to 42 days. Bonding of
      the experimental matrices with viable chondrocytes was achieved at 28 and 42
      days, as assessed by direct examination, histology, thymidine uptake, and
      fluorescence. No bonding occurred in the control composites without viable
      chondrocytes. We conclude that devitalized cartilage matrix is a scaffold to
      which isolated chondrocytes can attach and begin to repopulate.

PMID- 9565079
TI  - Increased content of type-VI collagen epitopes in human osteoarthritic cartilage:
      quantitation by inhibition ELISA.
AB  - Type-VI collagen is an integral part of the extracellular cartilage matrix.
      However, the exact amounts of type-VI collagen in normal and osteoarthritic human
      cartilage still are not known. In this study, we describe an inhibition enzyme
      linked immunosorbent assay that was developed to quantitate type-VI collagen
      epitopes found in guanidinium chloride extracts from normal and osteoarthritic
      human cartilage. In 31 cartilage samples from various localizations of healthy
      adult human knees, type-VI collagen epitopes accounted for approximately 0.40% of
      the total collagen content. Interestingly, type-VI collagen epitopes increased
      about 4-fold in osteoarthritic cartilage. A statistically significant increase of
      type-VI collagen epitopes was found during early stages of the disease, with only
      a superficial roughening of the cartilage surface and a loss of proteoglycans.
      Thus, these findings indicate that type-VI collagen is a minor component of
      normal human articular cartilage and that the amount of type-VI collagen epitopes
      increases significantly during early stages of osteoarthritis.

PMID- 9565080
TI  - Spatial and temporal expression of CD44 isoforms in the developing and growing
      joints of the rat limb.
AB  - Hyaluronan is an integral component of proteoglycan-rich extracellular matrices
      such as hyaline cartilage. Hyaluronan is commonly found in embryonic tissue and
      is important in the formation of hydrated matrices that allow cellular expansion
      and migration. Cell surface hyaluronan-binding proteins such as CD44 are presumed
      to be important in the cellular interactions with hyaluronan in both of these
      processes. The primary aim of this study was to document the spatial and temporal
      expressions of CD44 isoforms during the development and growth of the
      diarthrodial joints of rat limbs. With use of in situ hybridization and
      immunohistochemistry, the CD44s isoform is selectively identified as localized to
      a single cell layer on opposing sides of the joint at the first appearance of
      joint cavitation (on the 18th day of gestation). After joint formation in the
      neonate, the expression of the CD44s isoform in the cells at the joint surface is
      lost. These findings suggest that the CD44s isoform has a role in the development
      of the diarthrodial joint, presumably through interaction with hyaluronan.

PMID- 9565081
TI  - Generation of nitric oxide by lapine meniscal cells and its effect on matrix
      metabolism: stimulation of collagen production by arginine.
AB  - Slices of lapine meniscus produced large amounts of nitric oxide after
      stimulation with interleukin-1, tumor necrosis factor alpha, or a mixture of
      lapine synovial cytokines known as chondrocyte-activating factors. Monolayer
      cultures of meniscal cells produced from the proteolysis of meniscal tissue
      contained a mixed population of chondrocytic and fibroblastic cells. These
      cultures also produced large amounts of nitric oxide in response to cytokines.
      Monolayer cultures of meniscal cells produced by the explant method, in contrast,
      were uniformly fibroblastic and did not produce nitric oxide in response to
      cytokines. We conclude that menisci contain two populations of cells, one
      fibroblastic and the other chondrocytic. The chondrocytic cells are responsible
      for generating most of the nitric oxide in response to cytokines. Endogenously
      generated nitric oxide suppressed the synthesis of collagen and proteoglycan by
      menisci but protected proteoglycan from the catabolic effects of interleukin-1.
      The inhibitory effect of nitric oxide on collagen synthesis occurred without
      greatly altering the abundance of mRNAs encoding the various collagen alpha
      chains. During further investigation, arginine was unexpectedly found to
      stimulate the synthesis of collagen and, to a lesser degree, of noncollagenous
      proteins but not of proteoglycans. Fragments of meniscus, but not meniscal cells
      in monolayer culture, increased their production of matrix metalloproteinases,
      lactate, and, especially, prostaglandin E2 in response to interleukin-1.
      Inhibition of nitric oxide production with NG-monomethyl-L-arginine enhanced
      production of matrix metalloproteinases but had little effect on the synthesis of
      lactate or prostaglandin E2.

PMID- 9565083
TI  - Kinematics of the glenohumeral joint with Bankart lesion and repair.
AB  - A Bankart repair is performed to reduce abnormal translations of the humeral head
      on the glenoid due to a Bankart lesion, a separation of the capsulolabral complex
      from the glenoid rim. However, this is often accompanied by a loss of rotational
      range of motion that may lead to decreased function and osteoarthritis. This loss
      of rotation, coupled to the goal of reducing humeral translations, may be a
      result of the amount of imbrication of the capsule during repair. To determine
      the effects of capsular imbrication, we investigated how two Bankart repairs (2.5
      and 5.0 mm of capsular imbrication) and a Bankart lesion altered the translations
      and rotations of the human glenohumeral joint in vitro. Coupled moments were
      applied to the unconstrained humerus in abduction-adduction, in flexion
      extension, and to simulate the cocked phase of throwing. Motion was measured with
      an electromagnetic system. There were no differences in the kinematics between
      the intact specimens and those with a Bankart lesion or between normal specimens
      and the first (2.5 mm) Bankart repair. The first repair significantly reduced
      external rotation for the cocked phase of throwing compared with the Bankart
      lesion: from 46.8 +/- 23.6 degrees to 32.4 +/- 14.2 degrees (+/-SD). The second
      (5.0 mm) Bankart repair produced significantly different posterior translation (
      4.7 +/- 3.9 mm) of the humeral head relative to the glenoid compared with normal
      (5.1 +/- 4.7 mm anterior) and the first repair (6.1 +/- 8.3 mm anterior), as the
      humerus moved from full flexion to full extension. Differences were also found
      for all rotations in the cocked phase of throwing. For the second repair, the
      humerus extended 24.3 degrees and externally rotated 18.6 degrees less than
      normal and was abducted 15.4 degrees more. These results indicate that both
      Bankart repairs do little to affect humeral translations with unconstrained
      moment loading but that rotations are affected during the cocked phase of
      throwing, with significant losses of external and extension rotations.

PMID- 9565082
TI  - Fingertip loading and carpal tunnel pressure: differences between a pinching and
      a pressing task.
AB  - Carpal tunnel syndrome may be caused by repeated or sustained elevated carpal
      tunnel pressure. This study examined the relationship between carpal tunnel
      pressure, posture, and fingertip load. In 20 healthy individuals, carpal tunnel
      pressure was measured with a catheter inserted into the carpal tunnel of the
      dominant hand and connected to a pressure transducer. With the wrist in a
      pressure-neutral position, the subjects pressed on a force transducer with the
      index finger to levels of 0, 5, 10, and 15 N. They then pinched the transducer at
      the same levels of force. For both fingertip-loading postures, the carpal tunnel
      pressure increased with increasing fingertip load. Carpal tunnel pressures were
      significantly greater (p < 0.015) for the pinching task (14.2, 29.9, 41.9, and
      49.7 mm Hg [1.89, 3.99, 5.59, and 6.63 kPa] for 0, 5, 10, and 15 N force levels,
      respectively) than for simple finger pressing (7.8, 14.1, 20.0, and 33.8 mm Hg
      [1.04, 1.88, 2.67, and 4.51 kPa]). This study indicates that although the
      external load on the finger remained constant between the two tasks, the internal
      loading, as measured by carpal tunnel pressure, experienced a near 2-fold
      increase by using a pinch grip. These findings should be given consideration in
      designing work tasks and tools because relatively low fingertip forces,
      especially in a pinch grip, elevate carpal tunnel pressures to levels that, if
      prolonged, may lead to the development or exacerbation of carpal tunnel syndrome.

PMID- 9565084
TI  - Effect of combined axial compressive and anterior tibial loads on in situ forces
      in the anterior cruciate ligament: a porcine study.
AB  - This study investigated the impact of a combination of axial compressive and
      anterior-posterior tibial loads on the in situ forces in the anterior cruciate
      ligament. An axial compressive load is believed to contribute to increased
      stability of the knee joint; however, its effect on in situ forces in the
      anterior cruciate ligament has not been clearly defined, to our knowledge. It was
      hypothesized that the application of an axial compressive load, when combined
      with an anterior tibial load, would result in larger in situ forces in the
      anterior cruciate ligament than those caused by an isolated anterior tibial load.
      With use of a porcine knee model, the results confirmed this hypothesis; the
      addition of a 200 N axial compressive load to a 100 N anterior tibial load
      increased knee stability by reducing anterior-posterior tibial translation and
      internal-external tibial rotation and also caused a significant increase in in
      situ forces in the anterior cruciate ligament (p < 0.05). Specifically, there was
      a 34% increase in the in situ force at 30 degrees of flexion, a 68% increase at
      60 degrees of flexion, and an 84% increase at 90 degrees of flexion compared with
      those for an isolated anterior tibial load of 100 N. Additionally, there was a
      statistically significant increase of the in situ forces in the anterior cruciate
      ligament at 60 and 90 degrees as compared with those at 30 degrees. These results
      suggest that axial compressive loads on the knee may play a role in injury of the
      anterior cruciate ligament when the knee is flexed.

PMID- 9565085
TI  - Endothelin-1 is upregulated during skeletal muscle ischemia and reperfusion.
AB  - The aim of the present study was to test the hypothesis that the vasoconstrictive
      peptide endothelin-1 is upregulated in ischemia and reperfusion in skeletal
      muscle. Sixty-eight Wistar rats were included in the series: 12 served as
      controls that did not undergo the procedure, 16 underwent sham operations, and 40
      were subjected to a modified tourniquet ischemia for 3 hours and 20 minutes. Of
      the 40 rats, 16 were killed at the end of the ischemic period, 16 underwent
      reperfusion for 2 hours, and eight underwent reperfusion for 72 hours. Areas of
      necrosis were measured by morphometry in hematoxylin and eosin-stained cross
      sections of the anterior tibial muscles that had been reperfused for 72 hours.
      Sections from the controls, the muscles that had not been reperfused, and the
      reperfused muscles were immunostained for endothelin-1. Serum endothelin-1 levels
      in blood samples from the aorta were determined with a commercial enzyme
      immunoassay kit. The anterior tibial muscle was harvested for preproendothelin-1
      mRNA analysis with RNase protection assay. The hematoxylin and eosin-stained
      sections showed extensive necrosis with an acellular core of no reperfusion. The
      muscular core demonstrated weak immunostaining for endothelin-1 in all sections,
      a subfascial narrow brim of fibers showed enhanced immunoreactivity at the end of
      ischemia, and all fibers outside the core stained by 2 hours after the start of
      reperfusion. After 72 hours of reperfusion, the fibers outside the core stained
      positive in a checkerboard-like pattern. There were no differences in serum
      endothelin-1 levels between the groups. Preproendothelin-1 mRNA analysis with
      RNase protection assay showed 2-fold upregulation at the end of ischemia and 4
      fold upregulation after 2 hours of reperfusion (p = 0.001). This study supports
      the hypothesis that both ischemia and reperfusion upregulate endothelin-1 in
      skeletal muscle.

PMID- 9565086
TI  - Quantitative study of the quadriceps muscles and trochlear groove geometry
      related to instability of the patellofemoral joint.
AB  - This was a quantitative study of the major anatomical structures associated with
      instability of the patellofemoral joint: the quadriceps muscles and the femoral
      trochlear groove. The attachments of the muscles to the patella, their lines of
      action, and their relative sizes (physiological cross-sectional areas) were
      found. On the basis of the physiological cross-sectional areas, it was estimated
      that the central muscles-the rectus femoris and vastus intermedius-contributed
      35% of the quadriceps strength, with 40% from the vastus lateralis and 25% from
      the vastus medialis. The vastus lateralis had the most variable results, with the
      ratio of the lateralis to the medialis ranging from 0.90 to 2.18; this may be
      associated with patellar instability. Both the long and oblique parts of the
      vastus medialis were more oblique than the corresponding parts of the vastus
      lateralis. Photographic "skyline" views of the trochlear groove produced data on
      the sulcus angle and ratio of depth to width. The data showed that the trochlear
      groove did not deepen in the area contacted by the patella with progressive knee
      flexion (p > 0.53), contrary to popular belief. These data are useful for
      objective analysis of patellofemoral stability and related surgical
      interventions.

PMID- 9565087
TI  - Programmed removal of chondrocytes during endochondral fracture healing.
AB  - This investigation tested the hypothesis that the removal of chondrocytes during
      endochondral fracture healing involves an ordered process of programmed cell
      death. To accomplish this, unilateral closed fractures were created in the femora
      of 36 Sprague-Dawley rats. The rats were killed in groups of four on days 1, 3,
      7, 14, 21, 28, 42, 49, and 56 after fracture. The femora were embedded in
      paraffin and tested for expression of specific markers of fragmented DNA with use
      of a terminal deoxyuridyl transferase-mediated deoxyuridine triphosphate-biotin
      nick end labeling (TUNEL) technique. To determine the potential for
      transdifferentiation of chondrocytes to osteoblasts, calluses were also
      hybridized to detect expression of osteocalcin mRNA. Cell proliferation was
      assessed by an immunohistochemical detection method for proliferating cell
      nuclear antigen. A separate group of four rats was killed on day 28 to represent
      the later stage of the endochondral ossification, and the calluses were examined
      for cellular morphology with transmission electron microscopy. The results showed
      a coordination in both time and space of the activities of cellular proliferation
      and programmed cell death. Cell proliferation was most active in the earlier
      phases of fracture healing (days 1 through 14), although TUNEL expression was
      apparent in hypertrophic chondrocytes on day 14 after fracture and persisted
      until day 28. In the later stages of fracture healing (days 14 through 28),
      proliferating cell nuclear antigen was no longer synthesized in hard callus
      (intramembranous bone) and cell removal was the dominant activity in soft callus
      chondrocytes. Expression of osteocalcin mRNA was detected in osteoblasts but not
      in hypertrophic chondrocytes or in any other nonosteoblastic cell type. These
      findings support the hypothesis that the removal of chondrocytes during
      endochondral fracture healing is part of an ordered transition of tissue types in
      which the cellular mechanisms are genetically programmed to involve
      proliferation, maturation, and apoptotic cell death.

PMID- 9565088
TI  - Apoptosis, graft rejection, and transplantation tolerance.
AB  - Transplantation tolerance can be achieved through several mechanisms, including
      the action of suppressor cells, the induction of anergy, or the deletion of graft
      reactive donor T cells. In this article, the possible involvement of programmed
      cell death (apoptosis) in allograft rejection and transplantation tolerance is
      discussed. The recent characterization of members of the tumor necrosis factor
      alpha gene family has identified ligands (Fas ligand and TRAIL) and corresponding
      death receptors (DR). In rejected organ transplants, apoptotic cells are
      frequently encountered. Conversely, high-level expression of Fas ligand on the
      allograft correlates with graft acceptance in some models of organ
      transplantation. Furthermore, some of the immunosuppressive drugs currently in
      clinical use might exert their activity at least in part through effects on
      apoptotic pathways. From the available data, it can be inferred that apoptosis
      contributes to the outcome after organ transplantation, being involved both in
      graft rejection and in transplantation tolerance.

PMID- 9565089
TI  - Mechanisms of indirect allorecognition: characterization of MHC class II
      allopeptide-specific T helper cell clones from animals undergoing acute allograft
      rejection.
AB  - BACKGROUND: Recent evidence indicates that T cells primed via the indirect
      pathway of allorecognition play an important role in allograft rejection,
      although the effector mechanisms remain unknown. The purpose of this study was to
      characterize and study the in vivo function of self-restricted MHC allopeptide
      specific T-cell clones generated from animals undergoing allograft rejection.
      METHODS AND RESULTS: We generated self-restricted class II MHC allopeptide
      specific T-cell clones from the spleen and kidney of Lewis (LEW; RT1l) rats
      undergoing acute rejection of MHC-incompatible Wistar Furth (WF; RT1u) renal
      allografts. RT1.Du/beta20-44 peptide-specific CD4+ T helper 1 clones from the
      spleen and kidney of rejecting animals expressed a restricted T cell receptor
      (TCR) Vbeta repertoire: Vbeta4, 8.2, or 9. In comparison, clones generated from
      RT1.Dubeta20-44 immunized LEW rats all expressed TCR Vbeta9. The amino acid
      sequence of RT1.Dl (LEW) and RT1.Du (WF) residues 20-44 differ only at positions
      30 and 38. T-cell clones expressing TCR Vbeta9 preferentially proliferated to the
      peptide fragment RT1.Dubeta20-33. T-cell clones expressing TCR Vbeta4
      proliferated weakly to peptide fragments RT1.Dubeta20-33 and 31-44, whereas those
      expressing TCR Vbeta8.2 proliferated preferentially to the peptide fragment 31
      44. Adoptive transfer of T-cell clones expressing TCR Vbeta9 or Vbeta8.2, but not
      Vbeta4, to naive LEW animals elicited significant delayed-type hypersensitivity
      responses after challenge with the RT1.Dubeta20-44 peptide or allogeneic WF
      (RT1u) splenocytes. CONCLUSION: This is the first report on the cellular,
      molecular, and functional characterization of self-restricted MHC allopeptide
      specific T-cell clones from animals undergoing acute rejection. Our data provide
      support for a biologically significant role of indirect allorecognition in
      allograft rejection.

PMID- 9565090
TI  - Biochemical, pathological, and clinical response to transplantation of normal
      bone marrow cells into acid sphingomyelinase-deficient mice.
AB  - BACKGROUND: Acid sphingomyelinase knock-out (ASMKO) mice are a model of types A
      and B Niemann-Pick disease. In the present study, we evaluated whether bone
      marrow transplantation (BMT) carried out on newborn ASMKO mice could prevent or
      alter the Niemann-Pick disease phenotype. METHODS: Previous work from our
      laboratory had shown that ASMKO mice were highly susceptible to irradiation
      induced death. Therefore, we preconditioned 1-day-old ASMKO (n=35) mice with a
      "sublethal" dose of 200 cGy of total body irradiation before BMT. The
      transplantation effects were then analyzed by biochemical, pathological, and
      clinical approaches. RESULTS: Engraftment ranging from 7% to 100% was achieved in
      97% of the transplanted animals. Growth of the engrafted animals was improved,
      and their survival was increased (from a mean of 5 months to 9 months). The onset
      of ataxia also was delayed in most of the engrafted animals. In accordance with
      these observations, biochemical and pathological analysis revealed significant
      changes in the transplanted group as compared with nontransplanted animals. Lipid
      storage was reduced in several organs, and there was evidence of histologic
      improvement seen throughout the reticuloendothelial system, even in animals that
      were engrafted as low as 14%. In the central nervous system, lipid storage also
      was reduced, and the Purkinje cells, which are almost absent in ASMKO mice, were
      present in certain areas of the transplanted animals cerebella. CONCLUSIONS:
      These results demonstrated that BMT could alter the pathologic phenotype in ASMKO
      mice, but that this procedure alone was not sufficient to elicit a complete
      therapeutic effect.

PMID- 9565091
TI  - Possible induction of graft-versus-leukemia effect against a leukemia refractory
      to antileukemia response in ordinary MHC-compatible, allogeneic bone marrow
      transplantation.
AB  - We previously indicated that intensity of the graft-versus-leukemia (GVL) effect
      varied among different leukemias in MHC-compatible, allogeneic bone marrow
      transplantation (BMT). Cellular factors responsible for differences in intensity
      of the GVL effect were examined by using two types of leukemias, i.e., a
      resistant leukemia (LE750) and a sensitive leukemia (8313) to induction of the
      GVL effect in MHC-compatible, allogeneic BMT of leukemia-bearing host. Resistance
      of LE750 leukemic cells to induction of the GVL effect could not be attributed to
      either less sensitivity to lysis by minor H antigen-specific, cytotoxic T cells
      or to an immunosuppressive activity of LE750 leukemic cells in leukemia-bearing
      host, when compared with the case of the sensitive leukemia (8313). To
      investigate the significance of the dose effect of effector cells for induction
      of the GVL effect, we used CD8+ T cells of AKR donor mice, which were shown to
      preferentially induce the GVL effect with hardly any lethal graft-versus host
      disease against C3H recipient mice, enabling us to increase the number of CD8+ T
      cells used in the allogeneic donor inoculum. The results suggested that the
      outcome of the antileukemic response in allogeneic BMT of leukemic recipients may
      be determined, at least in part, by the balance between the size of leukemic
      cells surviving and repopulating in the recipients after BMT and the number of
      antileukemic effector cells. The results furthermore indicated that when donors
      with T-cell subsets that preferentially induce an antileukemic response with
      reduced graft-versus-host disease are available, a more effective antileukemic
      response is inducible even against advanced leukemias.

PMID- 9565092
TI  - Immunosuppressive effects of FTY720 alone or in combination with cyclosporine
      and/or sirolimus.
AB  - BACKGROUND: We examined the ability of FTY720, a novel immunosuppressant that
      prolongs the survival of allografts in experimental animal models, to potentiate
      the immunosuppressive effects of cyclosporine (CsA) and/or sirolimus (SRL) in
      vitro and in vivo. METHODS: FTY720 alone (10-5000 ng/ml) or in combination with
      other drugs was added to human peripheral blood lymphocytes (PBLs) undergoing
      stimulation in vitro with phytohemagglutinin (PHA) or OKT3 monoclonal antibody.
      The combination index (CI) values were calculated to evaluate the nature of the
      interactions between FTY720 and CsA and/or SRL: CI values <1 reflect synergistic,
      CI=1, additive, and CI>1, antagonistic interactions. In addition, Wistar Furth
      (RT1u) rat recipients of Buffalo (RT1b) heart allografts were treated with FTY720
      alone or in combination with other agents. FTY720 alone was also tested to block
      small bowel or liver allograft rejection in rats. RESULTS: FTY720 alone produced
      only modest inhibition of the proliferation of human PBL stimulated with PHA or
      OKT3 monoclonal antibody. In combination with CsA or SRL, however, FTY720
      produced synergistic effects, namely, CI values of 0.58 and 0.36, respectively. A
      14-day course of FTY720 (0.05-8.0 mg/kg/day) by oral gavage prolonged heart
      allograft survival in dose-dependent fashion. Although a 14-day oral course of
      CsA (1.0 mg/kg/day) alone was ineffective (mean survival time=7.0+/-0.7 vs. 6.4+/
      0.6 days in treated vs. untreated hosts), treatment with a combination of 1.0
      mg/kg/day CsA and 0.1 mg/kg/day FTY720 extended allograft survival to 62.4+/-15.6
      days (P<0.001; CI=0.15). Similarly, a 14-day oral course of 0.08 mg(kg/day SRL
      alone was ineffective (6.8+/-0.6 days; NS), but the combination of SRL with 0.5
      mg/kg/day FTY720 extended the mean survival time to 34.4+/-8.8 days (CI=0.28).
      The CsA/SRL (0.5/0.08 mg/kg/day) combination acted synergistically with FTY720
      (0.1 mg/kg/day) to prolong heart survivals to >60 days (CI=0.18). CONCLUSIONS:
      FTY720 potentiates the immunosuppressive effects of CsA and/or SRL both in vitro
      (by inhibiting of T-cell proliferative response) and in vivo (by inhibiting
      allograft rejection).

PMID- 9565094
TI  - To be or not to be a living donor: questionnaire to parents of children who have
      undergone renal transplantation.
AB  - BACKGROUND: Between 1981 and 1994, 67 transplantations were performed in 59
      children below 16 years of age at Huddinge University Hospital. In most of the
      cases, one of the parents was the donor. The aim of this study was to evaluate
      how the transplantation influenced the parents. METHODS: One hundred sixteen
      individual questionnaires were sent out to the donor parents and to the parents
      who for different reasons had not been donors. Of special interest was to
      investigate the emotional reactions, the social consequences, the relationship to
      the child, and the parents' attitudes toward donation. RESULTS: Thirty-five
      donors and 41 nondonors replied. The majority of both donors and nondonors were
      satisfied with the medical information. The nondonors expressed more stress and
      anxiety before the transplantation. More than half of the donors experienced the
      operation as more painful than they had expected. Despite this fact, the
      nondonors showed significantly more psychosomatic/psychiatric symptoms than the
      donors after the operation. The donors reported an improved relation to the
      recipient child after the transplantation to a greater extent than the nondonors.
      Half of the donors reported an improved self-esteem after the donation. None of
      the donors regretted their donation and all of them would do the same again.
      CONCLUSIONS: This study indicates that ethical and psychological risks in
      parental kidney donation should not be regarded as a major obstacle. However,
      irrespective of the parents being a donor or not, they wanted more psychosocial
      support both before, during, and after the transplantation.

PMID- 9565093
TI  - High-resolution characterization of cytokine-producing alloreactivity in naive
      and allograft-primed mice.
AB  - BACKGROUND: Whether alloreactive T cells in a naive host derive from naive or
      memory T cells remains unclear. It is also unclear whether graft rejection alters
      the phenotype of these T cells. Proliferation assays and cytokine enzyme-linked
      immunosorbent assays performed on culture supernatants do not differentiate
      primary T-cell alloreactivity from recall responses in allograft-primed mice,
      suggesting that these methods are inadequate measures of the alloreactive immune
      repertoire. METHODS: To better characterize alloreactivity in naive and skin
      allograft-primed mice, we used a modified, high-resolution cytokine enzyme-linked
      immunosorbent spot assay capable of detecting cytokine production over short time
      periods. RESULTS: Twenty-four-hour analysis of alloreactivity in mice that
      rejected fully MHC-disparate skin allografts revealed a high frequency of
      interferon (IFN)-gamma- and interleukin (IL)-4-producing, L-selectin-negative T
      cells, consistent with a memory phenotype. In contrast, 24-hr allostimulation of
      T cells from naive mice resulted in IL-2 production with minimal secretion of IFN
      gamma or IL-4. The frequency of IL-2 producers was low and their phenotype was L
      selectin positive, suggesting that they were naive and not memory T cells. When
      maintained in culture for 48 hr, however, the T cells from the primary mixed
      lymphocyte reaction began producing IFN-gamma, consistent with in vitro priming.
      CONCLUSIONS: The primary alloresponse does not seem to involve clones that have
      been preprimed by environmental antigens, but instead behaves similarly to self
      MHC-restricted immunity directed toward prototypic protein antigens: T cells with
      a naive phenotype are specifically induced to differentiate into high-frequency
      memory populations. These findings may have important implications for
      therapeutic induction of allograft tolerance.

PMID- 9565095
TI  - Effect of orthotopic liver transplantation on the progression of familial
      amyloidotic polyneuropathy.
AB  - BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant
      inherited disease associated with a mutant form of the protein transthyretin
      (TTR). It is characterized clinically by the systemic deposition of amyloid
      fibrils resulting in organ dysfunction and, ultimately, death. The majority of
      TTR is produced in the liver, and transplantation of the liver has been shown to
      ameliorate this source of mutant TTR, arresting the progression of this fatal
      disease. METHODS: Thirteen patients with FAP have undergone successful liver
      transplant surgery at our center since 1992. The impact of liver transplantation
      on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal
      dysfunction is reported in this study. Three patients who died before
      cardiovascular and neurological follow-up are excluded from the analysis.
      RESULTS: Ten of 13 patients (77%) remain alive an average of 49 months (range, 17
      64 months) after transplantation. Three patients suffered sudden death, with
      autopsy documentation of amyloid deposits involving the conduction system of the
      heart. Liver transplantation was performed more quickly, required less blood, and
      a shorter postoperative hospital stay in these patients, compared with patients
      with cirrhosis. Neurological and nutritional symptoms improved in the majority of
      affected patients. Those patients with echocardiographic evidence of ventricular
      wall and valve thickening before transplantation progressed postoperatively
      despite neurologic improvement. CONCLUSIONS: Liver transplantation offers the
      only cure for the genetic defect causing FAP and appears to result in subjective
      and objective improvement in neurological dysfunction. Patients with preexisting
      cardiovascular abnormalities progress despite transplantation; therefore,
      consideration for combined heart-liver transplantation may be warranted in this
      subset of patients.

PMID- 9565096
TI  - Long-term outcome of patients transplanted with livers from hepatitis C-positive
      donors.
AB  - BACKGROUND: The use of hepatitis C serology-positive donors has become an option
      in patients affected by hepatitis C (Hep C) end-stage liver disease. Previous
      studies with less than 1 year of follow-up have suggested that there is no
      difference in early patient and graft survival. The aim of our review is to
      confirm with a longer follow-up (a minimum of 1 year) that the use of these
      organs is safe and that patient and graft survival are comparable to those of
      patients with Hep C who received Hep C-negative grafts. METHODS: Between 1985 and
      1995, 213 patients were transplanted with a diagnosis of Hep C. Seventy-six
      patients were excluded from the study, 47 for insufficient follow-up and 29
      because the diagnosis of recurrence was not certain. Twenty-two patients received
      Hep C+ donor grafts and 115 patients received Hep C-donor grafts. These two
      groups were evaluated to assess the rate and severity of recurrence by serial
      biopsies and to assess patient and graft survival. RESULTS: Recurrent Hep C was
      documented by biopsy in 12 of 22 patients who received Hep C+ donor grafts. Of
      these 12 patients, 9 had mild chronic hepatitis, 2 had fibrosis, and 1 had
      cirrhosis. Ten of the 22 patients had normal biopsies. Of the patients who
      received Hep C- grafts, 48 of 115 had recurrent disease. Of these 48 patients, 23
      had mild chronic hepatitis, 15 had fibrosis, and 10 had cirrhosis. Sixty-seven of
      115 had normal biopsies. The recurrence rate was 54.55% in the Hep C+ donor
      grafts and 41.74% in the Hep C- donor grafts (P=NS). Patient and graft survival
      at 4 years after transplant were 83.9% and 71.9% in the Hep C+ donor grafts and
      79.1% and 76.2% in the Hep C- donor grafts, respectively (P=NS). CONCLUSIONS: Our
      study suggests that Hep C+ donors can be used with excellent long-term results
      and that the progression of the recurrent disease does not seem to be affected by
      the pre-existence of the Hep C virus in the donor.

PMID- 9565097
TI  - Impact of hepatitis C virus duration and hepatitis C virus genotypes on renal
      transplant patients: correlation with clinicopathological features.
AB  - BACKGROUND: The aim of this study was to evaluate the long-term impact of chronic
      hepatitis C virus (HCV) infection on the liver in renal transplant patients.
      METHODS: We studied 78 patients for whom at least one posttransplant liver biopsy
      (LB) was available and for whom the duration of HCV infection was precisely
      defined. The LB were graded according to a histological activity index, i.e., the
      Knodell score, divided into the activity score and the fibrosis score. They were
      also classified as either normal or showing evidence of chronic persistent
      hepatitis, chronic active hepatitis (CAH), or cirrhosis. RESULTS: The study
      comprised 7 HCV-positive/hepatitis B surface antigen-positive patients (group 1);
      4 HCV-positive/RNA-negative patients (group 2); and 67 HCV-positive/RNA-positive
      patients (group 3). The three groups were comparable according to demographic
      data and baseline immunosuppression. The median time from transplantation to LB
      was 38 months (range, 10-306 months). At that time, alanine aminotransferase
      (ALT) levels had increased in 71.4%, 0%, and 42% of patients from groups 1, 2,
      and 3, respectively (P=0.07). The total Knodell score showed significantly more
      severe lesions in group 1 patients (6.2+/-3.2) than in group 2 (1+/-1.2) or in
      group 3 (4.6+/-2.4) patients (P=0.007). The Knodell score also showed that the
      fibrosis score was significantly higher in group 1 (2.3+/-1.6) than in group 2
      (0) or in group 3 (0.9+/-1.1) patients (P=0.007). Overall, there were 28 cases of
      CAH (36%) and 4 cases of cirrhosis (5%). We did not observe any correlation
      between liver histology and characteristics of HCV infection or the type of
      chronic immunosuppression (double-drug versus triple-drug therapy). However,
      liver histology (total Knodell score) and the activity score were significantly
      correlated with ALT levels. Multivariate analysis did identify (i) four
      independent variables that could explain the degree of liver fibrosis-the sex of
      the patient, the number of blood units received before transplantation, increased
      ALT levels at the time of LB, and the occurrence of at least one acute rejection
      episode (thus the receipt of methylprednisolone pulses); and (ii) two independent
      variables associated with the occurrence of CAH-the number of blood units before
      transplantation and increased ALT levels at the time of LB. CONCLUSION: This
      study showed that renal transplant patients infected by HCV for more than 10
      years, with a mean posttransplant follow-up of more than 5 years, showed more
      severe liver lesions when coinfected by hepatitis B virus. Overall, we observed
      only four cases of cirrhosis (5%) and evidence of histological CAH lesions in 36%
      of the patients.

PMID- 9565098
TI  - Early loss of renal transplants in patients with thrombophilia.
AB  - BACKGROUND: We considered the possibility that thrombophilia may propagate graft
      thrombosis and therefore we evaluated the protein C system, which is a natural
      anticoagulant. Potential alterations in this system include protein C or protein
      S deficiency, inhibition through a lupus anticoagulant (LA), or a resistance to
      activated protein C due to the factor V Leiden (FVL) mutation. METHODS: One
      hundred thirty-two consecutive renal transplant patients, not known to have
      abnormal thrombostasis, in whom 1-year graft survival could be assessed,
      underwent laboratory testing for protein C or S activity, LA, and FVL. Transplant
      survival and demographic data were extracted from the hospital record. RESULTS:
      We identified 18 patients with thrombophilia (FVL, 10; LA, 6; protein S, 2) who
      had received a total of 28 renal transplants. Of these 28 transplant recipients,
      11 transplants were lost within the first year, compared with 21 of 155
      transplants to 114 patients without thrombophilia (P=0.0003). Median graft
      survival for patients with thrombophilia was 30 months (range: 0 to 166),
      compared with 86 months (range: 0 to 212) for patients without thrombophilia
      (P<0.01). The presence of thrombophilia represented a 3.5-fold (95% confidence
      interval, 2.3-5.3-fold) risk for 1-year graft loss. CONCLUSION: In this
      retrospective study, patients with thrombophilia had a significantly higher risk
      of early transplant failure. These data point toward a potential contribution of
      thrombophilia to transplant loss, a hypothesis that needs further study.

PMID- 9565099
TI  - Relative sedimentation of hematopoietic progenitors in human cord blood,
      peripheral blood, and bone marrow as determined by counterflow centrifugal
      elutriation.
AB  - BACKGROUND: The current use of cord blood (CB) and peripheral blood (PB) stem
      cells as alternatives or adjunctives to bone marrow (BM) for hematopoietic
      reconstitution in the treatment of various diseases prompted an examination of
      the progenitors of these tissues by counterflow centrifugal elutriation (CCE).
      METHODS: The cells, obtained from normal donors not primed with colony
      stimulating factors, were centrifuged at 3000 rpm in a Beckman Sanderson Chamber.
      Fractions (Frs.) were collected at (1) 18 ml/min, (2) 25 ml/min, (3) 32 ml/min,
      (4) 40 ml/min, and (5) the rotor-off fraction. RESULTS: Clonogenic assays
      revealed differences in the fraction localizations for CB and PB when compared to
      BM, i.e., recovery of the colony-forming units for CB and PB was greater in the
      small-medium cell size CCE fractions, and those from BM were found primarily
      among the medium-large cell size fractions. Thus, although colony-forming unit
      granulocyte/macrophage colonies were distributed throughout Frs. 2-5 of BM, CB
      and PB showed 80% of the total to be in Frs. 2 and 3. Further, although burst
      forming unit erythroid colonies of BM were distributed equally in Frs. 2 and 3,
      greater than 70% of the total burst-forming unit erythroid colonies in CB and PB
      were found in Fr. 2. Distribution of the CD34 cells in the fractions correlated
      with the colony-forming units in that these were found primarily in Frs. 2 and 3
      of CB and PB, whereas they were present in significant numbers throughout Frs. 1
      5 of BM. CONCLUSIONS: We interpret these findings to indicate CB and PB to be
      qualitatively similar in their hematopoietic lineage development and to contain a
      greater proportion of early versus late progenitors relative to those found in
      BM.

PMID- 9565100
TI  - Cellular immune responses of human cadaver donor bone marrow cells and their
      susceptibility to commonly used immunosuppressive drugs in transplantation.
AB  - BACKGROUND: The cascade of immunological effects brought about by donor bone
      marrow cell (DBMC) infusions in human organ transplantation, especially in the
      context of continuous pharmacologic immunosuppression, is not fully understood.
      Yet, in inbred rodents and even primates, administration of specific bone marrow
      cells has caused a state of acquired immunologic tolerance. METHODS: In vitro
      mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) culture
      systems were used to compare the responding and regulatory properties of DBMC and
      individual bone marrow cell subsets versus spleen cells in the presence or
      absence of pharmacologic immunosuppression. RESULTS: In the absence of
      immunosuppressive drugs, the DBMC proliferated in MLC and in response to
      phytohemagglutinin, but to a lower magnitude than donor spleen cells. In CML
      assays, DBMC failed to function as cytotoxic cells. Removal of both CD3+ and
      CD34+ cells together (not just singly) had to occur for complete abrogation of
      the proliferative response of DBMC evoked in the presence of allogeneic
      stimulating cells. Testing several experimental variables using flow cytometric
      analysis led to the conclusion that when purified DBMC CD34+ cells were placed in
      coculture with irradiated allogeneic peripheral blood mononuclear cells, such
      CD34+ cells give rise both to CD3- TCRalphabeta+ as well as to dimly staining
      CD3+ TCRalphabeta+ cells. Low pharmacologic concentrations of
      tacrolimus/cyclosporine (CsA) and mycophenolic acid (MPA) singly or in
      combination had no effect on the spontaneous proliferation of DBMC and had
      significantly less inhibitory activity on MLC responses of DBMC and its purified
      CD3+ or CD34+ subpopulations, compared with the responses of spleen cells.
      Moreover, the previously described regulatory effects of DBMC on the MLC
      responses of peripheral blood or splenic responding cells were not inhibited by
      these immunosuppressive drugs. CONCLUSIONS: Taken together, these results support
      the notion that in vitro DBMC subpopulations, which proliferate as responding
      cells in co-culture with x-irradiated allogeneic cells and which cause regulatory
      effects when added as a third component to MLC reactions, seem to be culture
      generated lymphoid cell lineage(s) progeny of CD34+ cells. This possibly includes
      unique CD3+ "primitive" (dimly staining) T cells, which are not as inhibited in
      their function by tacrolimus/CsA and MPA, as are postthymic (splenic) T cells.

PMID- 9565102
TI  - Microbiological evaluation of glycerolized cadaveric donor skin.
AB  - BACKGROUND: Human cadaveric donor skin is commonly used for the treatment of
      extensive burns. To minimize the risk of transfer of bacteria, viruses, and
      prions to the recipient, the donor and cadaver skin are screened according to
      standard transplantation protocols. METHODS: Since 1984, glycerol in a
      concentration of 85% has been used as a preservative of cadaver skin; here, data
      on bacteriological contamination of cadaver skin of 1929 skin donors are
      reviewed. RESULTS: Results show a reduction of contamination with 70% when
      antibiotics were used during the processing procedure. Overall, 10.1+/-4.1% of
      the cadaver skin showed initial bacterial contamination, but after prolonged
      storage all skin eventually showed no bacterial growth. The most commonly
      detected bacteria species was Staphylococcus epidermidis (76.7+/-7.0%). The spore
      forming Bacillus species was most resistant to inactivation by glycerol, but
      eventually also this species was no longer detected. CONCLUSIONS: In conclusion,
      preservation of skin in 85% glycerol reduces the risk of bacterial transfer to
      the recipient and allows an increase in yield of cadaver skin of approximately
      10%.

PMID- 9565101
TI  - Continuing observations on the regulatory effects of donor-specific bone marrow
      cell infusions and chimerism in kidney transplant recipients.
AB  - BACKGROUND: Continued follow-up of a series of donor bone marrow cell (DBMC)
      infused first cadaver renal transplant recipients is described (n=58), now at a
      36-month actuarial time point postoperatively. Serial polymerase chain reaction
      flow cytometry (PCR-Flow) and cellular immune assays of iliac crest bone marrow
      aspirates and peripheral blood have begun to be compared with concomitantly
      transplanted recipients of living-related donor (LRD) kidneys and donor marrow
      infusions given the same immunosuppressive regimen (n=16). There have also been
      comparisons (36 months) with 188 controls transplanted concomitantly, i.e.,
      recipients of first cadaver kidney transplants, who did not receive bone marrow.
      METHODS: Each group was given equivalent immunosuppressive regimens of OKT3 anti
      T cell induction and maintenance tacrolimus, mycophenolate mofetil, and
      methylprednisolone. Actuarial patient and graft survival have been 96% and 93%,
      respectively, in the controls and 91% and 91%, respectively, in the DBMC-infused
      recipients. Trough levels of tacrolimus were significantly lower in the DBMC
      infused group. RESULTS: In PCR-Flow measurements, in peripheral blood up to 6
      months postoperatively, there were higher levels of chimerism, i.e., in the total
      number of donor cells, as well as the donor CD3+ and CD34+ subsets in the LRD
      recipients administered DBMC infusions, compared with cadaver DBMC recipients,
      supporting the notion of a positive effect of histocompatibility on chimerism
      levels. In PCR-Flow measurements of recipient iliac crest bone marrow aspirates
      as in previous studies on peripheral blood, early acute rejection episodes (<1
      month) were found to be associated with a later (6-14 months) decrease in donor
      cell lineage chimerism. However, a trend toward recovery of chimeric levels
      occurred by 21-28 months in a second iliac crest marrow aspirate 1 year after the
      first aspirate in the DBMC-infused recipients who experienced such early
      rejection episodes. This was in contrast to the controls in whom there were
      sustained low levels of iliac crest bone marrow chimerism at both the earlier and
      later intervals (i.e., no chimeric recovery), with 17/183 surviving controls
      progressing into chronic rejection. This has not yet been seen in the DBMC
      infused group (0/54). In in vitro observations on cellular immune reactivity at 1
      year postoperatively, decreased peripheral blood lymphocyte proliferative
      reactions were seen in response to phytohemagglutinin and Staph-A mitogens, as
      well as to cytomegalovirus and Epstein-Barr viral protein antigens in the DBMC
      infused group versus the controls. Chronic immunosuppression did not seem to
      effect a vigorous in vitro inhibitory (regulatory) activity of bone marrow taken
      from these transplant recipients 2 years postoperatively in mixed lymphocyte
      culture and cell-mediated lympholysis reactions, using allogeneic responding
      cells from "normal" laboratory volunteers. Autologous peripheral blood
      lymphoproliferative responses to phytohemagglutinin and Staph-A mitogens, as well
      as to cytomegalovirus and Epstein-Barr virus protein antigens, were also
      regulated by either organ donor (non-immunosuppressed) bone marrow cells or by
      transplant recipient (immunosuppressed) bone marrow cells. What appeared to be
      disparate between the DBMC-infused and control groups (both immunosuppressed) was
      the trend for the (autologous) bone marrow suppressive effect on antiviral
      lymphoproliferative responses, to be stronger in the DBMC-infused group, who also
      had significantly (>one order of magnitude) higher levels of chimerism (P=0.01).
      CONCLUSIONS: It is concluded that the establishment of a chimeric state in DBMC
      infused recipients, albeit of relatively low magnitude (approximately 1% at 2
      years in recipient iliac crest bone marrow), has had a definite regulatory effect
      on immune responses. These results, therefore, add weight to the "causal" horn of
      the dilemma as to whether donor cell chimerism is a cause or an effect of

PMID- 9565103
TI  - Alpha-galactosyl epitope-mediated activation of porcine aortic endothelial cells:
      type II activation.
AB  - BACKGROUND: Xenoreactive natural antibodies (XNAs) and complement mediate
      hyperacute rejection of discordant xenografts. Inhibition of complement alone
      results in some prolongation of graft survival, but delayed xenograft rejection
      still precludes long-term graft survival. In vitro data provide evidence for the
      direct proinflammatory activation of endothelial cells (ECs) by XNAs. These
      antibodies are primarily directed against galactose alpha(1-3)-galactose (alpha
      gal), the major xenoantigen in the pig to primate xenotransplant model. Previous
      studies have shown EC activation by XNAs but failed to address the question of
      whether alpha-gal-specific ligands can induce EC activation. The aim of this
      study was to investigate whether agonist binding to the alpha-gal epitope by
      alpha-gal-specific lectins as compared with XNAs or elicited xenoreactive
      antibodies can directly elicit type II porcine aortic EC (PAEC) activation (i.e.,
      activation that requires protein synthesis). METHODS AND RESULTS: The
      tetravalent, alpha-gal-binding Bandeiraea simplicifolia lectin I (BS-I), the
      wholly alpha-gal-specific BS-I isolectin B4, and elicited primate anti-pig
      xenoreactive antibodies (decomplemented cynomolgus monkey anti-porcine serum)
      induced E-selectin protein expression in PAECs. This induction was alpha-gal
      specific, as preincubation with synthetic alpha-gal carbohydrate or adsorption of
      lectin or serum to rabbit, but not human, red blood cells removed the activating
      component. E-selectin expression, induced by BS-I, was inhibited in the presence
      of genistein, a tyrosine kinase inhibitor, and by mepacrine, an inhibitor of
      phospholipase A2. Human and primate XNAs lacked this activity when tested at
      relevant concentrations; however, stimulation of PAECs with affinity-purified
      human XNA (IgM and IgG) resulted in slightly increased interleukin-8 and P
      selectin mRNA levels but had no apparent effects on E-selectin transcription. BS
      I strongly induced E-selectin, P-selectin, intercellular adhesion molecule-1, and
      interleukin-8 mRNA in an NF-kappaB-dependent manner. CONCLUSIONS: Several
      agonists that specifically bind to alpha-gal can evoke type II EC activation.
      Hence, anti-Gal antibodies may contribute directly to xenograft rejection in the
      absence of complement activation.

PMID- 9565104
TI  - Association between interleukin-4-producing T lymphocyte frequencies and reduced
      risk of graft-versus-host disease.
AB  - BACKGROUND: We have previously developed and used limiting dilution analysis to
      measure frequencies of alloreactive cytotoxic T cell precursors (CTLp) and
      interleukin (IL)-2-producing T helper cells (IL-2/HTLp) to assess the risk of
      graft-versus-host disease in bone marrow transplantation (BMT). However, no test
      has been available to measure precursor frequencies of the important IL-4
      secreting subset. METHODS: We have now established a limiting dilution analysis
      to measure the frequency of IL-4-producing T helper cells (IL-4/HTLp) using the
      IL-4-responsive indicator cell line CT.h4S and have applied this assay to measure
      alloreactive IL-4/HTLp frequencies in BMT donor-recipient pairs. These
      frequencies were then analyzed in the context of clinical data to assess the
      relationship between the number of donor anti-recipient IL-4-secreting T cells
      and disease outcome. RESULTS: Frequencies of IL-4/HTLp have been studied in HLA
      identical siblings, HLA-"matched" unrelated, and HLA-mismatched combinations and
      found to range from approximately 1/500,000 in HLA-identical sibling pairs to 
      1/2,000 in HLA-DR-mismatched pairs. These frequencies were independent of those
      for IL-2/HTLp and showed a negative correlation with those for CTLp. Clinical
      follow-up of 30 patients showed that high IL-4/HTLp frequencies are associated
      with a reduced risk of severe graft-versus-host disease. High IL-4/HTLp
      frequencies may also indicate an increased risk of leukemia relapse. CONCLUSIONS:
      Our data suggest that measurement of IL-4/HTLp frequencies provides information
      distinct from that obtained with CTLp and IL-2/HTLp. This new assay provides a
      valuable additional method for optimizing donor selection in unrelated BMT.

PMID- 9565105
TI  - Effect of temperature on hepatic and renal uptake of components from University
      of Wisconsin solution.
AB  - In rat liver and kidney preservation, hepatic and renal uptake of 3H-adenosine,
      3H-glutathione, and 3H-raffinose from University of Wisconsin solution and
      diffusion to the interstitial space were measured. At 4 degrees C only 0.38+/
      0.47% and 2+/-0.92% of the total 3H-adenosine remained in the kidney and in the
      liver, respectively, but at 37 degrees C the amount remaining was 1+/-1% and 12+/
      3% (P<0.001). Hepatic and renal uptake of the impermeant 3H-raffinose was
      unaffected by temperature. During flush out, interstitial accumulation of
      adenosine was significantly higher in livers than in kidneys and decreased during
      24-h cold storage. Glutathione accumulation in the interstitial space was two
      orders of magnitude lower than 3H-adenosine accumulation and comparable to the
      impermeant raffinose. In summary, the bioavailability of components of
      preservation solutions at 4 degrees C is lower than at physiological
      temperatures, so that the application of cytoprotectants at 37 degrees C to organ
      donors, rather than simple addition to the cold storage solution, might improve
      cold storage preservation of livers and kidneys.

PMID- 9565106
TI  - Resolution of spur cell anemia with liver transplantation: a case report and
      review of the literature.
AB  - Spur cell anemia is an acquired hemolytic anemia, characterized by an increased
      percentage of abnormally shaped erythrocytes that are known as acanthocytes. The
      erythrocytes have numerous spicules irregularly distributed over the cell
      surface. Spur cell anemia has been described to occur in several conditions,
      including cirrhosis. We present an unusual case of a young patient with
      hemochromatosis, alcohol abuse, decompensated cirrhosis, and spur cell anemia who
      had a spontaneous resolution of the spur cell anemia after orthotopic liver
      transplantation. This finding suggests that the diseased liver may contribute to
      transformation of the erythrocyte to the spur cell.

PMID- 9565107
TI  - Risks associated with conversion of stable patients after liver transplantation
      to the microemulsion formulation of cyclosporine.
AB  - BACKGROUND: Neoral is a microemulsion formulation of cyclosporine that has a
      better pharmacokinetic profile than the standard formulation (Sandimmune). To
      prove the safety of converting stable liver transplant patients from Sandimmune
      to Neoral, we conducted a prospective trial involving 54 patients. METHOD: The
      average time from transplantation to conversion was 48.5+/-21.6 months. Thirty of
      54 patients (55%) required a dose reduction during the study for various reasons.
      Five of 30 patients had the first dose reduction because of increased levels of
      cyclosporine. Seven patients required more than one dose reduction. RESULTS:
      Sixteen patients suffered serious adverse events. Six patients had a biopsy
      proven rejection. Four of 6 patients had trough cyclosporine levels within 20% of
      baseline value immediately before developing rejection. CONCLUSION: Converting
      patients from the standard formulation to the microemulsion formulation of
      cyclosporine seems to expose stable patients to unnecessary risks.

PMID- 9565108
TI  - Successful treatment of severe hepatitis C-associated pulmonary vasculitis in a
      liver transplant recipient.
AB  - BACKGROUND: We report the clinical course of a patient who developed fever,
      hypoxia, and bilateral pulmonary infiltrates two and a half years after
      orthotopic liver transplantation (OLT) for cirrhosis due to hepatitis C. The
      patient had a history of hepatitis C-associated vasculitis manifested by purpuric
      skin rashes, renal abnormalities, and elevated cryoglobulins, and was receiving
      interferon-alpha at the time of presentation. RESULTS: The results of
      bronchoscopy with bronchoalveolar lavage were unrevealing, and open lung biopsy
      revealed active small vessel vasculitis. The patient responded dramatically to
      plasmapheresis and the addition of high-dose corticosteroids with resolution of
      hypoxia, pulmonary infiltrates, and glomerulonephritis. This is, to our
      knowledge, the first report of the successful treatment of hepatitis C-associated
      pulmonary vasculitis after OLT. CONCLUSIONS: We conclude that hepatitis C
      associated pulmonary vasculitis should be included in the differential diagnosis
      of a patient presenting with fever, hypoxia, and pulmonary infiltrates after OLT
      for hepatitis C. Treatment with plasmapheresis and high-dose corticosteroids may
      be effective in patients with this disorder.

PMID- 9565109
TI  - Peloisis hepatis due to Bartonella henselae in transplantation: a hemato-hepato
      renal syndrome.
AB  - BACKGROUND: Bacillary peliosis hepatis is an uncommon but well recognized disease
      due to disseminated Bartonella infections occurring predominantly in
      immunocompromised individuals infected with human immunodeficiency virus, type 1.
      A similar condition in the absence of Bartonella infection when described in
      organ transplant patients was felt to be secondary to azathioprine and/or
      cyclosporine. METHODS: Herein, we report the first case of bacillary peliosis
      hepatis due to systemic Bartonella henselae infection in a patient after kidney
      transplant. The patient presented with severe anemia, persistent
      thrombocytopenia, and hepato-renal syndrome. DNA-based polymerase chain reactions
      (PCR), which allowed direct detection of both B henselae and quintana DNA in
      patient's peripheral blood and liver tissue, were used. Indirect
      immunofluorescence assay for Bartonella serology was performed on peripheral
      blood. RESULTS: Histopathology of the liver biopsy demonstrated peliosis hepatis.
      Indirect immunofluorescence assay for Bartonella serology was positive, and B
      henselae DNA was identified by PCR in the peripheral blood and liver tissue.
      Treatment with a 3-month course of oral erythromycin resulted in an excellent
      clinical response. CONCLUSIONS: The present case suggests that although various
      anti-rejection therapies and opportunistic infections are associated with hepatic
      and renal dysfunction along with bone marrow suppression, the diagnostic
      evaluation in this situation should include liver biopsy and a careful search for
      evidence of systemic Bartonella infection, e.g., exposure to cats, Bartonella
      serology, and Bartonella DNA by PCR. A reduction in immunosuppression and
      prolonged therapy with antibiotics such as erythromycin will often result in
      early recovery.

PMID- 9565110
TI  - Immunohistochemical study of actin binding protein (p55) in the human kidney.
AB  - BACKGROUND: In clinical transplantation, "passenger" dendritic cells (DCs) in the
      allograft have been thought to induce allograft rejection. However, the presence
      of DCs in the normal human kidney is controversial. Most reports have relied on
      the examination of MHC class I and II antigen expression in combination with DC
      morphology for identification of DCs. METHODS: The distribution of the p55
      antigen (fascin), which is selectively expressed by human blood and lymphoid DCs,
      was investigated by immunohistochemistry. RESULTS: Our study demonstrates that
      p55-positive DCs are absent from the normal human kidney and CD1a- and S100
      positive cells are absent or very rare. Furthermore, HLA-DR and factor VIII
      related antigen show almost complete colocalization in capillaries. In contrast,
      all 16 kidney biopsies from patients with inflammatory processes demonstrated p55
      positive DCs in the cellular infiltrates. CONCLUSIONS: These results suggest that
      DCs are not present or are very rare in normal renal tissues but may migrate into
      the renal interstitium with inflammatory changes.

PMID- 9565111
TI  - Topical FK506 ointment for skin grafting.

PMID- 9565112
TI  - Recurrent collapsing glomerulopathy.

PMID- 9565113
TI  - The arduousness of excellence.

PMID- 9565114
TI  - Implications of peritoneal cytology for pancreatic cancer management.
AB  - OBJECTIVE: To assess the implications of positive cytology for malignant cells
      (positive results) from peritoneal washings in the management of patients with
      pancreatic cancer. DESIGN: Retrospective cohort study. SETTING: Referral practice
      in a university hospital. PATIENTS: A total of 32 consecutive pancreatic cancer
      patients with positive results from peritoneal washings during a 4-year period,
      17 with visible biopsy-proven intraabdominal metastases at the time of
      laparoscopy or laparotomy and 15 without visible metastases. A treatment-matched
      control group of 30 patients was randomly selected from a group of 105 patients
      with negative cytology for malignant cells (negative results) from peritoneal
      fluid cytology. INTERVENTIONS: Eight of 17 patients with visible metastases
      underwent treatment with chemotherapy, radiation, or both; 13 of the 15 patients
      with no visible metastases underwent further treatment, including pancreatic
      resection in 2 patients and external beam radiation in 13 patients (3 with
      intraoperative radiation therapy). MAIN OUTCOME MEASURES: Time to metastases and
      mortality. RESULTS: Median survival among patients with and without visible
      metastasis was 7.8 months and 8.6 months, respectively (P=.95), despite the fact
      that patients without visible metastases received more treatment. Patients
      without visible metastases at presentation were found to have metastatic disease
      as documented by computed tomographic scan or subsequent laparotomy at a median
      time of 2.9 months. The survival of treatment-matched patients with negative
      cytology was significantly longer (median, 13.5 months; P=.04). CONCLUSIONS:
      Pancreatic cancer patients with peritoneal micrometastases have a dismal outcome
      even without macroscopic metastases. Since these patients do not benefit from
      local therapy, the finding of a positive result from peritoneal-fluid cytologic
      testing contraindicates further irradiation or surgery, except for specific
      complications.

PMID- 9565115
TI  - Stereotactic core needle biopsy of nonpalpable breast lesions: initial experience
      with a promising technique.
AB  - OBJECTIVES: To evaluate the correlation between the pathological findings of
      stereotactic core needle biopsy (SCNB) and the prebiopsy mammographic findings,
      as well as the pathological findings of lesions that were subsequently removed by
      surgical excision. DESIGN: A retrospective review of 97 consecutive patients who
      underwent 100 SCNBs of suspicious nonpalpable mammographic lesions. The criterion
      standard is surgical excisional biopsy with needle localization. Mammographic
      findings were graded according to the American College of Radiology Breast
      Imaging Reporting and Data System. The pathological findings of SCNB were
      categorized into 4 groups: benign and specific, benign and nonspecific,
      premalignant, and malignant. Surgical excision of the lesion was performed if the
      pathological finding on SCNB was nonconcordant with the prebiopsy mammogram and
      when premalignant or malignant lesions were found. The pathological findings of
      lesions that were subsequently removed by surgical excision were compared with
      those of SCNB. SETTING: Community-based private multispecialty ambulatory
      practice. PATIENTS: A population-based sample composed of 97 patients who had
      grade III, IV, or V lesions on routine screening mammograms. INTERVENTION:
      Stereotactic core needle biopsy of nonpalpable mammographic lesions. MAIN OUTCOME
      MEASURES: Percentage of patients whose SCNB results were concordant with the
      mammographic findings and the pathological findings on subsequent surgical
      excision. RESULTS: Concordance between SCNB and mammography occurred in 97% of
      biopsy specimens. Concordance between the pathological findings of SCNB and those
      of surgically excised lesions occurred in 92.5% of biopsy specimens. We had 1
      false-negative result. We had no false-positive diagnosis of cancer with SCNB.
      CONCLUSION: On the basis of accumulating literature and our own initial
      experience, SCNB is a promising, safe, and cost-effective procedure.

PMID- 9565116
TI  - Is there a role for abdominal computed tomographic scans in appendicitis?
AB  - OBJECTIVE: To better define the effectiveness of abdominal computed tomographic
      scanning (ACTS) in adult patients with suspected appendicitis. DESIGN:
      Retrospective analysis. SETTING: A community teaching hospital. PATIENTS: Ninety
      seven patients with appendicitis in the differential diagnosis, whose clinical
      findings were insufficient to perform surgery or to discharge from the hospital,
      during a 14-month period. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Accuracy of
      ACTS, rate of appendectomies that show no appendicitis (negative appendectomy
      rate), and frequency of ACTS as a definitive diagnostic test. RESULTS: Forty-nine
      of the 50 patients with appendicitis were correctly diagnosed by ACTS. Forty
      three of the 47 patients without appendicitis were correctly diagnosed by ACTS.
      Positive predictive value was 92%, negative predictive value was 98%, and
      accuracy was 96%. The ACTS group had a negative appendectomy rate of 5.8% (3/52),
      lower than the hospital rate of 14% for the preceding 3 years. The ACTS
      established an alternative diagnosis in 16 patients, allowed 10 other patients to
      be discharged early or not admitted, and was the critical diagnostic test in 30
      of the patients with appendicitis. Therefore, the ACTS played a definitive role
      in the treatment of 56 (57.7%) of the 97 patients. CONCLUSIONS: The ACTS was an
      accurate test in the diagnosis of appendicitis and was of significant benefit in
      57.7% of the patients studied. However, it was difficult to predict which
      patients were most likely to benefit. Expanded selective use of ACTS for patients
      with clinically indeterminate appendicitis may result in a lower negative
      appendectomy rate and fewer patient admissions for observation.

PMID- 9565117
TI  - Long-term complications associated with prosthetic repair of incisional hernias.
AB  - OBJECTIVE: To determine whether the type of prosthetic material and technique of
      placement influenced long-term complications after repair of incisional hernias.
      DESIGN: Retrospective cohort analytic study. SETTING: University-affiliated
      hospital. PATIENTS: Two hundred patients undergoing open repair of abdominal
      incisional hernias with prosthetic material between 1985 and 1994. INTERVENTIONS:
      Four types of prosthetic material were used and placed either as an onlay,
      underlay, sandwich, or finger interdigitation technique. The materials were
      monofilamented polypropylene mesh (Marlex, Davol Inc, Cranston, RI), double
      filamented mesh (Prolene, Ethicon Inc, Somerville, NJ), expanded
      polytetrafluroethylene patch (Gore-Tex, WL Gore & Associates, Phoenix, Ariz) or
      multifilamented polyester mesh (Mersilene, Ethicon Inc). MAIN OUTCOME MEASURES:
      The incidence of recurrence and complications such as enterocutaneous fistula,
      bowel obstruction, and infection with each type of material and technique of
      repair were compared with univariate and multivariate analysis. RESULTS: On
      univariate analysis, multifilamented polyester mesh had a significantly higher
      mean number of complications per patient (4.7 vs 1.4-2.3; P<.002), a higher
      incidence of fistula formation (16% vs 0%-2%; P<.001), a greater number of
      infections (16% vs 0%-6%; P<.05), and more recurrent hernias (34% vs 10%-14%;
      P<.05) than the other materials used. The additional mean length of stay to treat
      complications was also significantly longer (30 vs 3-7 days; P<.001) when
      polyester mesh was used. The deleterious effect of polyester mesh on long-term
      complications was confirmed on multiple logistic regression (P=.002). The
      technique of placement had no influence on outcome. CONCLUSION: Polyester mesh
      should no longer be used for incisional hernia repair.

PMID- 9565118
TI  - Wound-induced tumor progression: a probable role in recurrence after tumor
      resection.
AB  - OBJECTIVE: To determine the effect of several wound factors on melanoma growth in
      a mouse model. DESIGN: Cohort analytic study. SETTING: Animal research facility
      of Roger Williams Medical Center, Providence, RI. STUDY GROUP: Seventeen groups
      of 5 C57BL/6 mice each. INTERVENTIONS: A surgical wound was created in 1 hind
      limb, after which different concentrations of B16F10 melanoma cells were injected
      in adjacent subcutaneous tissue. The nonwounded hind limb in the same mouse
      served as a control. In this fashion, a critical tumor cell dose was determined
      that showed tumor growth in the wounded but not the control hind limb. Tumor
      growth in control hind limbs then was compared with that in the "artificially
      wounded" hind limbs, which were co-injected with mouse wound fluid or growth
      factors. Early (day 1) and late (day 10) wound fluids and tumor growth factor
      beta (TGF-beta), basic fibroblast growth factor (bFGF), both combined, and
      interleukin 6 (IL-6) were used. MAIN OUTCOME MEASURE: Wound factors increase
      tumor growth, indicating potentiation of tumor recurrence at a surgical wound.
      RESULTS: The critical tumor cell dose was 10(3) cells. All growth factors and
      both wound fluids showed increased tumor growth over time except IL-6. Hind limbs
      injected with early wound fluid showed increased tumor growth over time when
      compared with those injected with late wound fluid (P<.001), TGF-beta (P<.001),
      bFGF (P<.001), and IL-6 (P<.001). Combined TGF-beta and bFGF co-injection
      resulted in increased tumor growth compared with TGF-beta (P<.001) and bFGF
      (P<.001), but did not differ significantly from early wound fluid (P<.07).
      CONCLUSIONS: The healing wound and its mediators in wound fluid or purified
      growth factors significantly enhanced tumor growth. Combining TGF-beta and bFGF
      increased tumor growth to a level closer to wound fluid. The inflammatory
      response provoked by wound healing mediators may be an important mechanism in
      tumor growth after ablative surgery.

PMID- 9565119
TI  - Delayed fluid resuscitation of head injury and uncontrolled hemorrhagic shock.
AB  - OBJECTIVE: To evaluate the effects of delayed vs early fluid resuscitation on
      cerebral hemodynamics after severe head injury and uncontrolled hemorrhagic
      shock. DESIGN: Prospective, randomized, controlled experimental trial. SETTING:
      Surgical research laboratory. PARTICIPANTS: Immature swine (N=16) weighing 40 to
      50 kg. INTERVENTIONS: Twelve swine were subjected to cryogenic brain lesion and
      hemorrhage to maintain a mean arterial pressure (MAP) of 50 mm Hg. Animals were
      randomized to receive 1 L of Ringer lactate solution in 20 minutes, starting 20
      minutes after injury and hemorrhage, followed by 1 L of Ringer lactate solution
      in 30 minutes (ER group) (n=6), or no fluid resuscitation (DR group) (n=6). The 4
      control animals underwent instrumentation only. The study ended 70 minutes after
      head injury and hemorrhage. MAIN OUTCOME MEASUREMENTS: Measurements of MAP,
      bilateral regional cerebral blood flow, serum hemoglobin level, systemic and
      regional cerebral oxygen delivery, and intracranial pressure performed at
      baseline and 20 (phase 1), 50 (phase 2), and 70 minutes (phase 3) after head
      injury and hemorrhage. Lesion size (percentage of ipsilateral cortex) was
      measured post mortem. RESULTS: All animals survived the experimental period.
      Systemic cerebral oxygen delivery in the DR group was significantly lower at
      phase 3 compared with that of the ER group (31.5% vs 53.1% at baseline) (P=.03).
      However, bilateral regional cerebral oxygen delivery was significantly greater in
      the DR group at phase 3 compared with that of the ER group (71.5% vs 47.0% at
      baseline in the injured side; 72.9% vs 48.4% at baseline in the noninjured side)
      (P=.02). Bilateral cerebral blood flow was similar in all groups at all times.
      The ER group showed a trend toward a greater intracranial pressure elevation (6.8
      vs -0.25) (P=.07) and lesion size (37.0% vs 28.6%) (P=.07). Hemoglobin level
      became significantly lower in the ER group at phase 2 (7.0 vs 10.7) (P=.03) and
      remained lower at phase 3 (6.9 vs 11.7) (P=.01). CONCLUSIONS: Early fluid
      resuscitation with Ringer lactate solution following head injury and uncontrolled
      hemorrhagic shock worsens cerebral hemodynamics. Cerebral pressure autoregulation
      is sufficiently intact following head injury to maintain regional cerebral oxygen
      delivery without asanguineous fluid resuscitation.

PMID- 9565120
TI  - Gut and liver: the organs responsible for increased nitric oxide production after
      trauma-hemorrhage and resuscitation.
AB  - OBJECTIVE: To determine which organs produce the increased levels of nitric oxide
      (NO) seen after hemorrhage and resuscitation. ANIMALS AND INTERVENTIONS: Adult
      male rats underwent laparotomy (ie, trauma induced) and were bled to and
      maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum
      bleedout volume was returned in the form of Ringer lactate. The rats were then
      resuscitated with Ringer lactate, 4 times the maximum bleedout volume for 1 hour.
      Sham-operated animals underwent only the surgical procedure. MAIN OUTCOME
      MEASURES: Plasma levels of nitrate/nitrite (NO3-/NO2-, stable products of NO)
      were measured by colorimetric assay at the maximum bleedout volume; at the end of
      hemorrhage; at the end of resuscitation; and 1.5, 4, 8, and 24 hours after
      resuscitation. In additional rats, the heart, liver, small intestine, kidneys,
      and spleen were harvested 4 hours after resuscitation for the measurement of NO3
      /NO2- levels. Moreover, tissue perfusion was determined in the above-mentioned
      organs by radioactive microspheres 4 hours after resuscitation in other groups of
      animals. RESULTS: Plasma levels of NO3-/NO2- were similar to those of sham
      operated animals during hemorrhage and at the end of resuscitation. One and a
      half hours after the end of resuscitation, however, NO production increased
      significantly. The peak levels of plasma NO3-/NO2- occurred at 4 hours, and the
      levels remained elevated even 24 hours after resuscitation. Tissue NO3-/NO2-
      levels were significantly increased in the liver, small intestine, and spleen 4
      hours after resuscitation. In contrast, the levels of NO3-/NO2- were similar to
      those of sham-operated animals in the heart and kidneys at all times. Blood flow
      in the heart was maintained after hemorrhage, whereas hepatic, intestinal,
      splenic, and renal perfusion decreased significantly. CONCLUSIONS: The gut and
      liver seem to be the sites responsible for the increased NO production seen after
      trauma and hemorrhage. The overproduction of NO is most likely caused by up
      regulation of inducible NO synthase. Thus, attempts to reduce NO production using
      specific inhibitors for inducible NO synthase might be helpful for improving
      hepatic and intestinal functions after trauma and hemorrhagic shock.

PMID- 9565121
TI  - Five-year follow-up of prophylactic vena cava filters in high-risk trauma
      patients.
AB  - OBJECTIVE: To assess the short- and long-term outcomes of vena cava filter (VCF)
      placement for prophylaxis against pulmonary embolism in patients at high risk due
      to trauma. DESIGN AND SETTING: Case series at a level I trauma center. PATIENTS:
      Patients were considered for prophylactic VCF placement if they met 1 of the
      injury criteria--spinal cord injuries with neurologic deficit, severe fractures
      of the pelvis or long bone (or both), and severe head injury--and had a
      contraindication to anticoagulation. INTERVENTION: Vena cava filters were placed
      percutaneously by the interventional radiologists when the acute trauma condition
      was stabilized following admission. MAIN OUTCOME MEASURES: Filter tilt of 14
      degrees or more, strut malposition, insertion-related deep vein thrombosis,
      pulmonary embolism, or inferior vena cava patency. RESULTS: There were 132
      prophylactic VCFs placed. A 3.1% rate of insertion-related deep vein thrombosis
      occurred, all of which were asymptomatic. Filter tilt occurred in 5.5% of
      patients and strut malposition in 38%. Three cases of pulmonary embolism (1
      fatal) occurred in a prophylactic VCF, and all patients had either filter tilt or
      strut malposition. The risk of pulmonary embolism developing was higher in those
      patients with filter tilt or strut malposition than in those who did not have
      these complications (6.3% vs 0%; P=.05; Fisher exact test). The 1-, 2-, and 3
      year inferior vena cava patency rates (+/-SD) were 97%+/-3%. CONCLUSIONS:
      Prophylactic VCF can be placed safely with an acceptable rate of insertion
      related deep vein thrombosis and long-term inferior vena cava patency. Patients
      with prophylactic VCF remain at risk for pulmonary embolism if the filter is
      tilted 14 degrees or more or has strut malposition. In such patients,
      consideration should be given to placing a second filter.

PMID- 9565122
TI  - Metastases to the pancreas and their surgical extirpation.
AB  - BACKGROUND: The pancreas is an unusual but occasionally favored site for
      metastases, notably from carcinomas of the kidney and lung. The pancreas may be
      the only identified locus of spread, and therefore may provide an opportunity for
      significant palliation or even cure using pancreatectomy. OBJECTIVE: To report
      the treatment and outcome of patients presenting with metastases to the pancreas.
      DESIGN: Five-year survey. SETTING: Tertiary referral center. PATIENTS: Ten
      patients with apparently isolated metastases to the pancreas were identified from
      January 1, 1991, to December 31, 1995. All patients were followed up until death
      or to September 1997. RESULTS: The patients had been treated previously for
      carcinoma of the lung (n=4), renal cell carcinoma (n=2), sarcoma (n=2), breast
      carcinoma (n=1), and endometrial carcinoma (n=1). The interval between primary
      treatment and presentation of the metastases averaged 70 months (14-24 months for
      lung cancer, 10 and 22 years for renal cell carcinoma, 4 and 6 years for sarcoma,
      8 years for breast cancer, and 36 months for endometrial carcinoma). Metastases
      were initially misdiagnosed as primary pancreatic cancers in 7 patients. In 4
      patients (those with renal cell cancer and sarcomas), the tumor was completely
      resected using total pancreatectomy (n=3) or Whipple resection (n=1). Survival
      after diagnosis averaged 22 months. Two of the 4 patients undergoing pancreatic
      resection remain alive and well 20 and 25 months after pancreatectomy.
      CONCLUSIONS: The pancreas may be the presenting and perhaps sole locus for
      metastasis, typically years after treatment for certain extrapancreatic malignant
      neoplasms. Recognition and surgical treatment can provide worthwhile palliation
      and long-term survival.

PMID- 9565123
TI  - Differentiated thyroid cancer: reexamination of risk groups and outcome of
      treatment.
AB  - OBJECTIVE: To reexamine the age, metastases, extent, and size (AMES) risk
      criteria for well-differentiated thyroid cancer with the effect of therapy on
      outcome. DESIGN: Review of patient medical records and direct-contact follow-up.
      SETTING: Two tertiary referral centers. MAIN OUTCOME MEASURES: Recurrence or
      death. PATIENTS: One thousand nineteen patients with well-differentiated thyroid
      cancer treated between 1940 and 1990. RESULTS: One thousand nineteen patients
      with well-differentiated thyroid cancer were treated between 1940 and 1990, with
      a mean follow-up of 13 years, including a recent group of 264 patients treated
      from 1980 to 1990 at 2 different institutions with a mean follow-up of 8 years.
      The AMES criteria were used to designate high- and low-risk patients. The entire
      group had 229 high- and 790 low-risk patients; the percentage of high-risk
      patients decreased slightly after 1960. From 1940 to 1960, 1960 to 1979, and 1980
      to 1990, the high-risk groups had survival rates of 48%, 62%, and 47%,
      respectively. For the low-risk patients, survival rates were 96%, 98%, and 98%,
      respectively. Recurrences occurred in 5% of low-risk patients and were usually
      curable; in high-risk patients, recurrence was associated with a 75% mortality.
      In low-risk patients, there was no significant difference in recurrence or death
      according to type of operation (unilateral or bilateral) or use of radioactive
      iodine. In high-risk patients, there were trends toward but no significant
      improvement in survival with bilateral surgery and radioactive iodine therapy;
      thyroid replacement was associated with a significant improvement in survival.
      CONCLUSIONS: The AMES risk criteria remain highly valid predictors of risk. They
      define most low-risk patients for whom radical treatment may add excess morbidity
      but not improve already excellent prognoses.

PMID- 9565124
TI  - Two hundred one consecutive living-donor nephrectomies.
AB  - OBJECTIVE: To assess donor morbidity, recipient outcome, and changing trends
      during the past decade in donor nephrectomy for living-donor kidney
      transplantation. DESIGN AND SETTING: Retrospective review at an academic tertiary
      care referral center. PATIENTS: We reviewed 201 consecutive living-donor kidney
      transplantations performed between January 1988 and June 1997. INTERVENTION:
      Donor nephrectomy and living-donor kidney transplantation. MAIN OUTCOME MEASURES:
      Donor surgical complications, correlation of preoperative imaging of donor
      vascular anatomy and operative findings, and donor lengths of stay in the
      hospital were analyzed. Recipient delayed graft function and actuarial 1- and 5
      year patient and graft survival rates were also analyzed. RESULTS: Major donor
      postoperative complications were bleeding (0.5%), pneumothorax requiring a chest
      tube (1%), wound infection (1%), and pneumonia (1%). Minor postoperative
      complications were asymptomatic pneumothorax resolving spontaneously (10%),
      urinary retention (6%), and urinary tract infection (0.5%). Preoperative imaging
      failed to detect small accessory renal arteries in 12% of donors. The mean donor
      length of stay in the hospital was 5.0 days but decreased from 6.2 to 4.0 days
      during the study. Twenty donors (10%) were unrelated (ie, spouse or friend).
      Three (1.5%) cases of delayed graft function occurred. Overall recipient patient
      survival at 1 and 5 years was 97% and 90%, and graft survival was 95% and 83%,
      with no difference between related and unrelated living donors. CONCLUSIONS:
      Living-donor nephrectomy is associated with low surgical morbidity. Recent trends
      include shortened lengths of stay in the hospital, the use of computed
      tomographic angiography instead of digital subtraction angiography for
      preoperative imaging of donor vascular anatomy, and an expanded use of unrelated
      living donors.

PMID- 9565125
TI  - Preemptive pain control in patients having laparoscopic hernia repair: a
      comparison of ketorolac and ibuprofen.
AB  - OBJECTIVES: To determine if nonsteroidal anti-inflammatory drugs provide adequate
      pain control for patients having laparoscopic hernia repair and to compare the
      effectiveness of ketorolac tromethamine with ibuprofen in reducing postoperative
      laparoscopic hernia pain. DESIGN AND SETTING: Prospective double-blind randomized
      study at a 100-bed community hospital. PATIENTS: Seventy patients ranging in age
      from 16 to 83 years scheduled for elective laparoscopic inguinal hernia repair.
      INTERVENTIONS: Patients undergoing laparoscopic hernia repair were enrolled in a
      double-blind randomized study to compare the 2 treatments. Group 1 received a
      placebo capsule 1 hour before surgery and ketorolac tromethamine, 60 mg
      intravenously, at the time of trocar insertion. Group 2 received ibuprofen, 800
      mg an hour before surgery, and isotonic sodium chloride solution, 2 mL
      intravenously, at the time of trocar insertion. In addition, all patients
      received local infiltration of 30 mL of bupivacaine hydrochloride into their
      trocar sites. All patients were discharged within 5 hours of the operation and
      were instructed to take 400 mg of ibuprofen orally every 4 hours for 24 hours
      whether or not they were experiencing pain. A 24-hour supply of ibuprofen was
      provided to all study patients. Pain was assessed using the Visual Analog Pain
      Scale with a maximum pain rating of 100. Assessments were done at the time of and
      18 hours after discharge. MAIN OUTCOME MEASURE: Postoperative pain 18 and 24
      hours after discharge was assessed using a standardized questionnaire in a
      telephone interview by a registered nurse from the Outpatient Surgical Unit.
      RESULTS: There was no significant difference in the level of pain experienced by
      35 patients who received ketorolac intravenously and 35 who received ibuprofen
      orally. There was no significant difference between the 2 treatment groups in the
      amount of pain experienced at discharge and 18 hours after discharge.
      CONCLUSIONS: Pain relief from ibuprofen, 800 mg, administered orally an hour
      before laparoscopic hernia repair was not statistically different from that
      obtained with intravenous ketorolac, 60 mg, administered intraoperatively when
      comparing the hospital discharge pain score and the mean and highest pain scores
      18 hours after discharge. Ibuprofen offers equivalent pain control at a lower
      cost and reduced potential for adverse drug events compared with intravenous
      ketorolac in patients having laparoscopic hernia repair. No patient required
      narcotic supplementation, and pain control was judged satisfactory by all the
      patients.

PMID- 9565126
TI  - Novel potentiation of interleukin 1alpha production in endotoxin-stimulated IC-21
      cells by ambient pressure augmentation.
AB  - BACKGROUND: We hypothesized that increased ambient pressure would increase the
      production of interleukin 1alpha by endotoxin-stimulated macrophages, based on
      the clinical observation that patients with "pus under pressure" demonstrate
      systemic toxic effects (a priori hypothesis). DESIGN AND SETTING: In vitro
      experiment in the laboratory. INTERVENTIONS: A murine macrophage line, IC-21
      cells, was seeded into 6-well plates, 25 x 10(4) cells per well. Cells were
      incubated under atmospheric (ATM) or increased (ATM+60 mm Hg) ambient pressure
      (AP) in the presence or absence of endotoxin (lipopolysaccharide [LPS]). The IC
      21 production of interleukin 1alpha was determined at 2, 4, 8, and 12 hours. Four
      groups were examined: group 1: AP ATM, no LPS; group 2: AP ATM+60 mm Hg, no LPS;
      group 3: AP ATM and LPS, 500 ng/mL; and group 4: AP ATM+60 mm Hg and LPS, 500
      ng/mL. MAIN OUTCOME MEASURES: The IC-21 production of interleukin 1alpha.
      RESULTS: Interleukin 1alpha production at 2, 4, 8, and 12 hours (mean [+/-SD]
      picograms per 10(6) cells) was as follows: group 1: 3.0 (+/-5.9), 8.1 (+/-10.3),
      50.5 (+/-51.1), and 6.1 (+/-4.1), respectively; group 2: 228.7 (+/-110.2), 141.0
      (+/-141.8), 112.5 (+/-98.5), and 118.2 (+/-79.8), respectively; group 3: 37.2 (+/
      13.3), 191.5 (+/-86.5), 627.3 (+/-184.3), and 600.7 (+/-67.1), respectively; and
      group 4: 601.2 (+/-49.9), 1050.9 (+/-190.6), 2684.2 (+/-562.2), and 3144.7 (+/
      388.4), respectively. The production of IL-1alpha by group 3 was significantly
      greater (P<.04, unpaired Student t test) at 4, 8, and 12 hours than that by
      groups 1 or 2. Likewise, the production of IL-1alpha by group 4 was significantly
      greater (P<.001, unpaired Student t test) at all time points than that by groups
      1, 2, or 3. CONCLUSIONS: Our data support the hypothesis that pressure may be a
      novel potentiator of the macrophage proinflammatory cytokine response to
      endotoxin. This provides a possible explanation for the phenomenon of systemic
      illness seen with "pus under pressure."

PMID- 9565127
TI  - Reexploration for hemorrhage following coronary artery bypass grafting: incidence
      and risk factors. Northern New England Cardiovascular Disease Study Group.
AB  - OBJECTIVE: To assess mortality and risk factors associated with reexploration for
      hemorrhage in patients undergoing coronary artery bypass grafting (CABG). DESIGN:
      Regional cohort study. Patient characteristics, treatment variables, and outcome
      measures were collected prospectively. SETTING: All 5 centers performing cardiac
      surgery in Maine, New Hampshire, and Vermont. PATIENTS: A consecutive cohort of
      8586 patients undergoing isolated CABG between 1992 and 1995. MAIN OUTCOME
      MEASURES: Postoperative hemorrhage leading to reexploration, in-hospital
      mortality, and length of stay. RESULTS: A total of 305 patients (3.6%) underwent
      reexploration for bleeding. In these patients, in-hospital mortality was nearly 3
      times higher (9.5% vs 3.3% for patients not requiring reoperation, P<.001) and
      average length of stay from surgery to discharge was significantly longer (14.5
      days vs 8.6 days, P<.001). High rates of reexploration for hemorrhage were
      observed in patients with prolonged (> 150 minutes) cardiopulmonary bypass (39
      [11.1%] of 351) and in those requiring an intra-aortic balloon pump
      intraoperatively (12 [8%] of 139). In multivariate analysis, older age, smaller
      body surface area, prolonged cardiopulmonary bypass, and number of distal
      anastomoses were associated with increased bleeding risks. The use of
      thrombolytic therapy within 48 hours of surgery was weakly but not significantly
      associated with the need for reexploration. Factors not significantly associated
      with reexploration included patient sex, preoperative ejection fraction, surgical
      priority, history of liver disease, myocardial infarction, prior CABG, renal
      failure, and diabetes mellitus. CONCLUSIONS: Hemorrhage requiring reexploration
      after CABG is associated with markedly increased mortality and length of stay.
      Patients predicted to have increased risks of bleeding may benefit from
      prophylactic use of aprotinin, aminocaproic acid, or other agents shown to reduce
      hemorrhage.

PMID- 9565128
TI  - Laparoscopic common bile duct exploration: practical application.
AB  - OBJECTIVE: To evaluate the effectiveness of laparoscopic common bile duct
      exploration in unselected patients. DESIGN: Consecutive sample. SETTING: Tertiary
      care general hospital. PATIENTS: Three hundred and two patients with symptomatic
      cholelithiasis presenting to a single surgeon during a 5-year period.
      INTERVENTIONS: Laparoscopic cholecystectomy, cholangiography, and common bile
      duct exploration. MAIN OUTCOME MEASURES: Successful laparoscopic cholecystectomy
      and common bile duct exploration. RESULTS: Three hundred and two consecutive
      patients underwent cholecystectomy for symptomatic cholelithiasis; 280 of the
      procedures were successfully completed laparoscopically. Cholangiography was
      attempted in 269 patients, was successful in 239, and revealed evidence of
      choledocholithiasis in 25. Preoperative ultrasonography and liver function tests
      predicted the presence of common bile duct stones in 24% and 32% of patients,
      respectively. Seven of the patients with choledocholithiasis presented with
      biliary colic, 7 with biliary colic and jaundice, 8 with acute cholecystitis (3
      with gallbladder perforation), 1 with acute cholecystitis and jaundice, and 2
      with gallstone pancreatitis. Four of 5 patients underwent successful transcystic
      exploration with a biliary Fogarty catheter, 12 of 16 patients underwent
      successful transcystic choledochoscopy and stone basket extraction, and all 4
      attempts at choledochotomy and choledochoscopic stone basket extraction were
      successful, for a total success rate of 80% with laparoscopic common bile duct
      exploration. One of the failures was converted to an open procedure, and 4 of the
      failures had successful postoperative endoscopic retrograde
      cholangiopancreatography and extraction of stones. CONCLUSIONS: Laparoscopic
      cholecystectomy and common bile duct exploration is a highly successful procedure
      for the management of common duct stones in an unselected group of patients.
      Choledochotomy with choledochoscopy is the preferred method of common bile duct
      exploration.

PMID- 9565129
TI  - Effective treatment of lymphedema of the extremities.
AB  - OBJECTIVE: To define the immediate and long-term volumetric reduction following
      complete decongestive physiotherapy (CDP) for lymphedema. DESIGN: Prospective
      study of consecutively treated patients. SETTING: Freestanding outpatient
      referral centers. PATIENTS: Two hundred ninety-nine patients referred for
      evaluation of lymphedema of the upper (2% primary, 98% secondary) or lower (61.3%
      primary, 38.7% secondary) extremities were treated with CDP for an average
      duration of 15.7 days. Lymphedema reduction was measured following completion of
      treatment and at 6- and 12-month follow-up visits. INTERVENTION: Complete
      decongestive physiotherapy is a 2-phase noninvasive therapeutic regimen. The
      first phase consists of manual lymphatic massage, multilayered inelastic
      compression bandaging, remedial exercises, and meticulous skin care. Phase 2
      focuses on self-care by means of daytime elastic sleeve or stocking compression,
      nocturnal wrapping, and continued exercises. MAIN OUTCOME MEASURES: Average limb
      volumes in milliliters were calculated prior to treatment, at the end of phase 1,
      and at 6- to 12-month intervals during phase 2 to assess percent volume
      reduction. RESULTS: Lymphedema reduction averaged 59.1% after upper-extremity CDP
      and 67.7% after lower-extremity treatment. With an average follow-up of 9 months,
      this improvement was maintained in compliant patients (86%) at 90% of the initial
      reduction for upper extremities and lower extremities. Noncompliant patients lost
      a part (33%) of their initial reduction. The incidence of infections decreased
      from 1.10 infections per patient per year to 0.65 infections per patient per year
      after a complete course of CDP. CONCLUSIONS: Complete decongestive physiotherapy
      is a highly effective treatment for both primary and secondary lymphedema. The
      initial reductions in volume achieved are maintained in the majority of the
      treated patients. These patients typically report a significant recovery from
      their previous cosmetic and functional impairments, and also from the
      psychosocial limitations they experienced from a physical stigma they felt was
      often trivialized by the medical and payor communities.

PMID- 9565130
TI  - Intravenous leiomyomatosis with caval involvement: report of a case with radical
      resection and venous replacement.
AB  - Intravenous leiomyomatosis is a rare, histologically benign neoplasm that may be
      malignant in its specific tendency to intravascular extension. A case of
      intravenous leiomyomatosis with extension into the entire inferior vena cava in a
      41-year-old woman is described. The patient was diagnosed with syncope 3 years
      after hysterectomy and was treated with a 1-stage procedure including venous
      replacement.

PMID- 9565131
TI  - Principles in the operative treatment of pressure sores.

PMID- 9565132
TI  - Abdominal gunshot wounds and diagnostic peritoneal lavage.

PMID- 9565133
TI  - Pentoxifylline in sepsis.

PMID- 9565134
TI  - The American surgical instrument trade in the aseptic era.

PMID- 9565135
TI  - Characterization of alpha2-adrenoceptor subtypes in pregnant human myometrium.
AB  - The aim of the present investigation was to determine which subtypes of the
      alpha2-adrenoceptors are being expressed in the human pregnant myometrium at term
      pregnancy. In radioligand binding studies, the specific binding of
      [3H]rauwolscine to human myometrial membranes was specific and of high affinity
      with Kd of 2.8 +/- 0.6 nMand Bmax of 95 +/- 5 fmol/mg protein. Results from
      competition for the binding of [3H]rauwolscine using subtype-selective ligands,
      oxymetazoline (alpha2A-subptype), chlorpromazine (alpha2B-subtype) and prazosin
      (alpha2B-alpha2C-subtype), suggested that the alpha2A- and alpha2B-subtypes are
      being co-expressed. In order to examine if also the alpha2C-subtype is being
      expressed we used an optimal concentration of oxymetazoline or chlorpromazine
      which would block the high-affinity site, equivalent to the alpha2A- and alpha2B
      subtype respectively. Competition curves of both oxymetazoline and chlorpromazine
      still showed a significantly better fit using a two-site model, suggesting that
      the alpha2C-subtype also is being expressed. The expression of alpha2C-subtype
      mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA
      isolated from myometrial biopsies. In conclusion, our results suggest that all
      three subtypes of alpha2-adrenoceptors are being coexpressed in the human
      myometrium at term pregnancy and that alpha2-expression is dominated by the
      alpha2A-subtype.

PMID- 9565136
TI  - Sexual difference in early fetal crown-rump length versus gestational age in
      pregnancies arising from in vitro fertilization.
AB  - The purpose of this study was to investigate the influence of fetal sex on the
      crown-rump length (CRL) derived from pregnancies resulting from in vitro
      fertilization without the uncertain conception dating in the first trimester.
      With ultrasonography, we performed 334 and 353 examinations, on 88 male and 102
      female fetuses, respectively. The relationship between gestational age and fetal
      CRL was explored with regression analysis: male CRL (mm) = 1.13 x gestational age
      (days) - 47.39 (r = 0.97), female CRL = 1.11 x gestational age - 46.44 (r =
      0.97). These regression lines were mutually included in the 95% confidence
      intervals for each other. Our results indicate no statistically significant
      difference in the CRL between the two sexes, being supportive of using the
      identical fetal CRL criterion regardless of fetal sex for gestational age
      assessment with ultrasonography in the first trimester of pregnancy.

PMID- 9565137
TI  - Local application of methotrexate for ectopic pregnancy with a percutaneous
      puncturing technique.
AB  - Management of ectopic pregnancy remains traditionally surgical. Early detection
      of unruptured ectopic pregnancies, using both ultrasound techniques and beta
      human chorionic gonadotropin (beta-hCG) assays, allows a more conservative
      treatment. Twenty-six tubal pregnancies, which were managed with local
      methotrexate (MTX) injection, are presented. A single dose of 10-12.5 mg of MTX
      was percutaneously injected into the gestational sac under abdominal sonographic
      control. Complete resolution was obtained in all our patients. Four of them
      required a second percutaneous administration 4 days after the first one.
      Negligible serum beta-hCG levels (< 10 mIU/ml) were reached within 42 days after
      treatment. No systemic side effects were observed. Local administration of MTX
      under abdominal sonographic control seems to be an effective alternative for the
      treatment of ectopic pregnancy. The main potential advantages of the method are
      (1) a greater antitrophoblastic effect; (2) a shorter treatment period; (3)
      reduced dosage, and (4) absence of side effects.

PMID- 9565138
TI  - Three-dimensional ultrasonographic assessment of the umbilical cord during the
      2nd and 3rd trimesters of pregnancy.
AB  - OBJECTIVE: To evaluate the umbilical cord and its abnormalities by use of three
      dimensional ultrasonography with a specially developed abdominal three
      dimensional transducer. PATIENTS AND METHODS: Ninety-five pregnancies (92 normal,
      2 with hydrops fetalis, and 1 with omphalocele) from 14 to 40 weeks of gestation
      were studied with a specially developed abdominal three-dimensional transducer
      (3.5 MHz). This system can provide conventional two-dimensional ultrasonography
      images and can also generate within seconds high-quality three-dimensional images
      in the surface and transparent mode with no need for an external workstation. A
      proportion of the umbilical cords (coiled or noncoiled free loop, abdominal
      insertion, and placental insertion) visualized at each gestational age interval
      is presented. RESULTS: The proportion of the umbilical cords visualized during
      pregnancy except for between 24 and 27 weeks of gestation was about 70% (range 64
      83%). Optimal visualization of the umbilical cord was achieved between 24 and 27
      weeks of gestation. During this period it was possible to adequately depict the
      umbilical cord in 93% of the cases. The proportions of the noncoiled umbilical
      cord depicted during pregnancy ranged from 8 to 45%. The detection rate of
      abdominal insertion of the umbilical cord visualized at 14-19 weeks was 44%; the
      detection rate decreased thereafter. Placental insertion of the umbilical cord
      could not be identified after 28 weeks of gestation. In 2 cases with hydrops
      fetalis, edematous umbilical cord was evident. In 1 fetus, omphalocele was
      clearly depicted. CONCLUSIONS: The new three-dimensional ultrasound technology
      generates within seconds high-quality three-dimensional images of the umbilical
      cord, although limitation of viewing direction exists. These results suggest that
      the new three-dimensional ultrasonography has the potential to be a supplement to
      two-dimensional ultrasonography and might be useful in identifying abnormal
      umbilical cords in utero.

PMID- 9565139
TI  - Comparative changes in uterine artery blood flow waveforms in singleton and twin
      pregnancies.
AB  - We prospectively studied 99 women with uncomplicated singleton pregnancies and 24
      women with uncomplicated twin pregnancies to examine the effect of the location
      of the placenta on the pulsatility index (PI) in the uterine arteries in twin
      pregnancies and to compare singleton and twin pregnancies with regard to changes
      in the PI of uterine arteries over the course of the pregnancy. The flow velocity
      waveforms in both the right and left parametrial uterine arteries were recorded
      longitudinally at 2-week intervals from a gestational age of 19 weeks until
      delivery. The location of the placenta was determined by real-time
      ultrasonography at 18-20 weeks of gestation to determine which uterine artery was
      the ipsilateral artery. In both the ipsilateral and contralateral uterine
      arteries, the PI exhibited a steady decrease toward term in singleton
      pregnancies. In twin pregnancies, the PI exhibited a steady decrease until 27
      weeks of gestation and remained unchanged thereafter. The PI in the ipsilateral
      artery was consistently lower than that in the contralateral artery in singleton
      as well as twin pregnancies. The mean values of PI of the ipsilateral and
      contralateral uterine arteries of twin pregnancies was consistently lower than
      that of singleton pregnancies at any gestational week. These results suggest that
      the ipsilateral uterine artery contributes more to placental perfusion than does
      the contralateral uterine artery in twin as well as in singleton pregnancies.
      Twin pregnancies differed from singleton pregnancies with respect to changes in
      PI in the uterine artery according to gestational age. The PI of uterine arteries
      declined more rapidly and reached a plateau earlier in twin than in singleton
      pregnancies.

PMID- 9565140
TI  - Preeclampsia and maternal heart rate variability.
AB  - Maternal heart rate variability was evaluated by means of 24-hour Holter ECG
      monitoring in three groups of patients (15 preeclamptic, 15 women hospitalized
      due to other complications and 15 normal ambulatory pregnant women) in the 28th
      33rd week of gestation. Heart rate variability was estimated by time and
      frequency domain measures. Patients with preeclampsia had significantly longer NN
      intervals during daytime compared to the other groups studied. With regard to
      frequency domain measures such as very-low-frequency, low-frequency and high
      frequency power, the groups did not differ. Nor did they differ with regard to
      day and nighttime. We conclude that during pregnancy, the power of the maternal
      heart rate spectrum is markedly depressed, which affects the power of the method
      to separate normal pregnancies from pregnancies affected by preeclampsia.

PMID- 9565141
TI  - Evaluation of glucose intolerance in pregnancy using biochemical markers of fetal
      hyperinsulinemia.
AB  - We aimed to evaluate gestational impaired glucose tolerance (GIGT) in untreated
      patients using umbilical cord blood insulin and connecting peptide (C-peptide)
      concentrations to indicate fetal hyperinsulinemia. A 75 g, 2-hour oral glucose
      tolerance test, evaluated using WHO criteria, was performed in 722 antenatal
      patients. Cord C-peptide (p = 0.001) and insulin (p = 0.008) concentrations were
      significantly higher in patients with GIGT in comparison to those with normal
      glucose tolerance. The WHO test failed to identify abnormal C-peptide
      concentrations (p = 0.057), but did identify abnormal insulin concentrations (p =
      0.006) and cases where either or both were raised (p = 0.002), with a low
      Youden's index (range 8.1-11.3) in all 3 cases. A significant biochemical
      difference exists in patients with GIGT. The WHO criteria for GIGT predict
      abnormal biochemical outcomes, but they do so poorly.

PMID- 9565142
TI  - Effect of the duration of labor on postpartum postvoid residual bladder volume.
AB  - In order to investigate the possibility of protracted labor as a risk factor for
      postpartum urinary retention and to study the relation between duration of labor
      and postpartum day 1 postvoid residual bladder volume, the postpartum postvoid
      residual bladder volume (PVRBV) of a group of patients was studied using
      ultrasonography. Out of 707 patients investigated during a 2-month study period,
      a homogeneous group of 164 patients, with possible risk factors for postpartum
      urinary retention being controlled, was studied. The homogeneous group's
      postpartum day 1 postvoid residual bladder volumes were assessed by
      ultrasonography and analyzed with respect to the duration of labor. The incidence
      of postpartum urinary retention ( > or = 150 ml) was 11% in this homogeneous
      group. Labor duration longer than or equal to 800 min was associated with a
      higher incidence of postpartum urinary retention (chi2 test; p < 0.05). Moreover,
      there is a direct relationship between the duration of labor and PVRBV which is
      described by a quadratic regression curve. Protracted labor longer than or equal
      to 800 min is a risk factor for postpartum urinary retention. The PVRBV is
      directly related to the duration of labor.

PMID- 9565143
TI  - Childbirth as a biological model for stress? Associations with endocrine and
      obstetric factors.
AB  - OBJECTIVE: The aims of this investigation were to measure corticotropin-releasing
      hormone (CRH), corticotropin (ACTH) and cortisol before, during and after
      delivery searching for an endocrine intercorrelation of the hypothalamic
      pituitary-adrenal (HPA) axis and to correlate these findings with obstetrical
      variables. METHODS: Blood was sampled from 50 women with singleton pregnancies at
      term without uterine contractions, during delivery (after full cervical
      dilatation) and on the 4th postnatal day. Hormones were measured by
      radioimmunoassay (RIA). The correlation between obstetric variables,
      sociodemographic and endocrine data were evaluated using the Spearman rank
      coefficient. Group comparisons for continuous variables were calculated using the
      Mann-Whitney U test and Kruskal-Wallis test. RESULTS: Maternal plasma ACTH and
      cortisol increased significantly during labor, declining toward the 4th postnatal
      day (p < 0.001) and showing a significant intercorrelation (p < 0.01). Compared
      to women without uterine contractions CRH rose during labor (p < 0.05) and
      decreased rapidly to the 4th postnatal day (p < 0.001). No correlations between
      CRH and ACTH or cortisol were observed. None of the obstetrical variables
      (parity, newborn's weight, duration of delivery) revealed any significant
      correlation with ACTH. Analgetic medication (pethidine hydrochloride) was not
      able to influence the endocrine response to labor stress. CONCLUSIONS: Stressful
      experience during childbirth has an impact on endocrine response. However, this
      is not fully evident along the HPA axis in a simple biological model with
      monocausal dependencies. This 'biological stress model' is not sensitive enough
      to detect different childbirth conditions and the hormones in the maternal
      compartment have partially fetal (placental) origin.

PMID- 9565144
TI  - Ovarian stimulation with low-dose pure follicle-stimulating hormone in polycystic
      ovarian syndrome anovulatory patients: effect of long-term pretreatment with
      gonadotrophin-releasing hormone analogue.
AB  - A randomised clinical trial was performed to evaluate the effect of a 3-month
      gonadotrophin-releasing-hormone analogue (GnRH-a) in one cycle of ovulation
      induction with low-dose pure follicle-stimulating hormone (pFSH) in patients with
      polycystic ovarian syndrome (PCOS) anovulation. Twenty patients with chronic
      anovulation due to PCOS were randomised to ovulation induction with pFSH
      administered in a low-dose schedule with (10 patients) and without (10 patients)
      a 3-month pretreatment with GnRH-a. Ultrasound scan only monitoring of follicular
      growth, evaluation of plasmatic oestradiol at the day of triggering of ovulation
      with human chorionic gonadotrophin 5,000 IU and evaluation of plasmatic
      progesterone 8 days after were the main outcome measures. Ovulation occurred in 9
      patients treated with pFSH and in 2 patients treated with GnRH-a plus pFSH. Five
      pregnancies in the pFSH group and no pregnancy in the GnRH-a group were obtained.
      Five cycles were stopped due to multifollicular growth in the GnRH-a group and 1
      in the pFSH group. Pretreatment with a 3-month administration of a GnRH-a did not
      improve the ovulation rate and pregnancy rate in PCOS patient ovulation induction
      with low-dose pFSH.

PMID- 9565145
TI  - Evaluation of the accuracy of transvaginal sonography for the assessment of
      retained products of conception after spontaneous abortion.
AB  - Transvaginal sonography (TVS) was used to assess uterine contents in 100
      consecutive subjects presenting with a diagnosis of spontaneous abortion. TVS
      assessments were correlated with findings at subsequent evacuation of retained
      products of conception (ERPC). There was a strong correlation between the weight
      of the surgical specimen at ERPC with both the sagittal (r = 0.76; p < 0.05) and
      transverse (r = 0.73; p < 0.05) plane area measurements of the uterine cavity.
      Combining the 2 sonographic measurements increased the correlation to r = 0.81 (p
      < 0.05). Fifteen of 25 subjects who had been categorised to have an 'empty'
      uterus had less than 5 g of tissue removed and the other 10 subjects less than 10
      g of tissue. In 20 of these 25 cases, the surgeon described the amount of
      curettings as 'small or non-significant'. TVS can accurately identify those women
      who do not have a significant amount of residual uterine tissue following
      spontaneous abortion.

PMID- 9565146
TI  - Transcervical fallopian tube recanalization under fluoroscopic guidance. The
      Iwasaki-Hayashi catheter.
AB  - This study was designed in order to assess whether the Iwasaki-Hayashi (IH)
      catheter can be fixed to the uterine cervix easily and successfully during
      transcervical fallopian tube recanalization (T-FTR) with fluoroscopic guidance,
      to try T-FTR in special cases, and to investigate the success rate. The study
      included 21 infertile women with tubal obstruction, diagnosed by
      hysterosalpingography examined at least twice to exclude tubal spasm. Using the
      IH catheter, which proved to be very useful, higher therapeutic efficacy could be
      obtained. A patient with unilateral proximal tubal obstruction became pregnant
      following natural fertilization in the fallopian tube which had been recanalized
      by T-FTR. The success rate of recanalization, the pregnancy rate and the take
      home-baby rate were 95.2%/patient, 19.0 and 19.0%, respectively.

PMID- 9565147
TI  - Transvaginal ultrasonographic evaluation of the endometrium related to the
      histological findings in pre- and perimenopausal women.
AB  - OBJECTIVE: To evaluate the clinical usefulness of high-resolution transvaginal
      ultrasonography in pre- and perimenopausal women suspected to have endometrial
      pathology. PATIENTS AND METHODS: 196 women, aged between 32 and 57 years, were
      referred to the outpatient clinic for a dilatation and curettage (D&C). In 81%
      the clinical indication was irregular vaginal bleedings. Before the D&C an
      examination with transvaginal ultrasonography was performed, and the endometrial
      thickness and texture were determined. The ultrasonographic results were later
      compared with the histological diagnosis obtained from the D&C specimen. RESULTS:
      Ultrasonographically both normal and pathological endometrial changes could be
      detected, and 82% of the women had an endometrium characterized as normal. The
      endometrial phase determination correlated with the histological findings in
      approximately 50% of the women. Histologically 83% of the women had a normal
      endometrium. Endometrial hyperplasia was found in 12% and endometrial polyps in
      4%. There were no malignancies found in this study. The hormone users (33% of the
      women) had no higher incidence of hyperplasias than non-users. CONCLUSION: Our
      data indicate that transvaginal ultrasonography is as effective as the D&C for
      depicting the endometrium in pre- and perimenopausal women with irregular
      bleedings.

PMID- 9565148
TI  - How alarming is post-coital bleeding--a cytologic, colposcopic and
      histopathologic evaluation.
AB  - This retrospective analysis studies post-coital bleeding (PCB) in 110 patients
      presenting to the colposcopy clinic of the University College of Medical Sciences
      and Guru Teg Bahadur Hospital, Delhi, India, and covers a 2-year period from
      March 1994 to February 1996. All the patients were evaluated by cytology and
      colposcopy. Colposcopy-positive patients underwent a directed biopsy. Age, parity
      and duration of PCB were correlated with histopathologic findings, i.e. benign
      changes, viral HPV changes and cervical intra-epithelial neoplasia (CIN) 1, CIN 2
      and 3 and invasive cancer for risk assessment. 85.5% of the patients had benign
      findings, 5.6% viral HPV and CIN 1, 3.6% CIN 2 and 3 and 5.5% invasive cancer.
      Vascular ectopy was the commonest benign colposcopic finding. Cytology had a
      sensitivity and specificity of 56% and 90%, respectively. The mean age of
      patients with invasive cancer was 41.3 years versus 32.9 years in patients with
      benign pathology, the difference being statistically significant (p < 0.05). Mean
      parity was 4.2 in patients with invasive cancer against 2.8 in benign cases (NS).
      There was no correlation between duration of bleeding and pathology.

PMID- 9565149
TI  - Cushing's syndrome in pregnancy secondary to adrenal adenoma. A case report and
      literature review.
AB  - We describe a case of Cushing's syndrome complicating pregnancy presented with
      acute heart failure, hypertension and glucose intolerance. A left adrenal adenoma
      was removed at 24 weeks of gestation. The pregnancy was ended with an emergency
      lower-segment Caesarean section at 31 weeks of gestation because of severe pre
      eclampsia and HELLP syndrome. The case is reported not only because of its rarity
      but also to induce the discussion of surgical treatment during pregnancy.

PMID- 9565150
TI  - Power Doppler findings of adenoma malignum of uterine cervix.
AB  - Adenoma malignum (minimum deviation adenocarcinoma) is a rare neoplasma of the
      uterine cervix, the diagnosis of wich cannot be determined by cervical smear.
      Recently, magnetic resonance imaging (MRI) was reported as useful for its
      diagnosis, but differentiation of adenoma malignum from deep-seated nabothian
      cysts remains problematic. We report here a case of adenoma malignum of the
      uterine cervix, for which MRI findings could not neglect deep-seated nabothian
      cysts. However, transvaginal power Doppler ultrasonography clearly showed
      richness of small vessels, whose arterial flow had higher velocity in the
      diastolic phase, around the cystic lesion of the uterine cervix. These findings
      indicate that, at least in the case reported here, transvaginal power and pulsed
      Doppler ultrasonography is a useful tool for the diagnosis of adenoma malignum of
      the uterine cervix.

PMID- 9565151
TI  - Introduction: from the genetic basis of blood disorders to gene transfer for the
      purpose of gene therapy.

PMID- 9565152
TI  - Understanding alpha globin gene expression: a step towards effective gene
      therapy.
AB  - During the past 20 years developments in molecular and cellular biology have
      kindled the hope that one might eventually ameliorate or even cure some serious
      genetic diseases by repairing or replacing the defective gene. Other articles
      deal with the formidable problems of isolating pluripotent hematopoietic stem
      cells; efficiently, safely, and stably transfecting them, and developing
      transplantation protocols to ensure that the corrected cells supplant the
      patient's abnormal stem cells after transplantation. Assuming that these hurdles
      can be overcome, it will also be important to establish the ideal segment of DNA
      to introduce into stem cells to ensure that, regardless of its position of
      integration in the genome, the gene in question will be appropriately regulated.
      In the case of the globin genes this is a particularly difficult task because in
      order to correct disorders of globin synthesis we need to obtain high levels of
      stable, tissue- and developmental-stage specific expression. Issues relevant to
      this problem arising from the analysis of the human beta globin cluster are
      discussed in the article in this issue by Grosveld. In this article we review our
      current understanding of how eukaryotic genes might be expressed from their
      normal chromosomal environment, using the human alpha globin cluster as a
      specific example. We also discuss how this information might be used in the
      development of strategies for gene therapy.

PMID- 9565153
TI  - The dynamics of globin gene expression and gene therapy vectors.
AB  - The most important level of the regulation of the beta-globin genes is by
      activation of all of the genes by the locus control region (LCR). Part of the
      developmental regulation of the locus is achieved by competition of the genes for
      the interaction with the LCR. Although this level of gene regulation is
      quantitatively of less importance than the direct repression mechanism for the
      early genes, it has important implications and has provided an excellent assay to
      probe the regulation of transcription at the single cell level. The results of
      these studies indicate that the LCR interacts with individual globin genes and
      that LCR/gene interactions are dynamic with complexes forming and dissociating
      continually. We conclude that transcription only appears to take place while the
      LCR and gene interact and that the level of transcription is determined by the
      frequency and duration of such interaction rather than by changes in the rate of
      transcription of the promoters. This mechanism has clear implications for the
      design of vectors for the purpose of gene therapy.

PMID- 9565154
TI  - Genetic treatment of severe hemoglobinopathies: the combat against transgene
      variegation and transgene silencing.
AB  - Gene addition strategies are rational approaches to the treatment of sickle cell
      anemia and thalassemia. The goal of such genetic treatments is to introduce a
      functional globin transcription unit in hematopoietic stem cells and express the
      transgene in a manner that is erythroid-specific, elevated, relatively constant
      from one cell to another, and sustained over time. Gene transfer is mediated by
      an expanding array of viral and nonviral vectors. High-titer retroviral vectors
      harboring the human beta-globin gene and the core sequences of the human beta
      globin locus control region yield erythroid-specific gene expression in erythroid
      cell lines and in short-term murine bone marrow chimeras. However, we show that
      expression remains subject to position effect variegation and often decreases
      over time in vivo. Rather than a progressive transcriptional silencing in all
      cells, we ascribe the waning expression to the gradual emergence in blood of
      erythroid progeny derived from more and more primitive precursor cells in the
      months after transplantation. In our model, transgene expression is therefore
      determined by the integration site and the differentiation stage of the
      transduced cell at the time of integration. Globin expression is thus different
      in the progeny of a transduced erythroid progenitor cell and in the erythroid
      progeny of a transduced hematopoietic stem cell, reflecting the effect of
      flanking chromatin in differentiated cells and of chromatin remodeling at the
      site of integration in the progeny of multipotential cells. This model predicts
      that insulators and matrix attachment regions could be highly valuable to gene
      therapy in combination with potent transcriptional activators. When efficient
      gene transfer in hematopoietic stem cells is achieved at last, the challenge will
      be to regulate gene expression in vivo and overcome transgene variegation and
      transgene silencing.

PMID- 9565155
TI  - Red cell enzyme deficiencies: from genetic basis to gene transfer.
AB  - Features of some of the more common erythrocyte enzyme deficiencies that may be
      relevant to possible future attempts to correct the deficiencies by gene transfer
      approaches are considered. The last few years have seen rapid progress in our
      understanding of the molecular basis of these diseases and the regulation of the
      genes underlying these deficiencies is now coming into focus. Animal models for
      some of the conditions are available and others can be produced by homologous
      recombination techniques. Although considerable improvements in gene transfer
      vectors and protocols are required, this research may lead eventually to gene
      replacement therapy for these severe conditions.

PMID- 9565156
TI  - Knocking in and out genes and trans genes: the use of the engineered mouse to
      study normal and aberrant hemopoiesis.
AB  - Mouse genetics and engineered mice have become invaluable tools for the study of
      normal and aberrant hemopoiesis, in modeling hemopoietic disorders, and
      developing new therapeutic approaches using these models. However, the
      technological exploitation of these powerful genetic tools, as well as the
      scientific exploitation of the mutants which are generated is still in a
      primordial phase. For instance, the possibility to introduce specific point
      mutation, in vivo, in any desired locus, will allow the production of a second
      generation of mutants, which will be much more informative in the dissection of
      the function of any molecule. Furthermore, the possibility to interbreed mutants
      thus generating organisms harboring concomitantly "n" mutations in "n" loci will
      allow the possibility to test and validate, in vivo, the role of individual
      biochemical and cellular pathways.

PMID- 9565157
TI  - Somatic mutation and clonal selection in the pathogenesis and in the control of
      paroxysmal nocturnal hemoglobinuria.
AB  - Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a somatic mutation
      of the X-linked PIG-A gene which occurs in a hematopoietic stem cell. This
      results in a proportion of blood cells being deficient in all glycosyl
      phosphatidylinositol (GPI) anchored proteins. These GPI-deficient cells explain
      many of the clinical symptoms of PNH, but not the mechanism that enables the PNH
      clone to expand. In vitro bone marrow culture studies, molecular analysis of the
      genetic lesions, and data derived from mice with PNH blood cells demonstrate that
      PIG-A inactivation alone does not confer a proliferative advantage to the
      hematopoietic stem cell. Thus, a second factor is needed to cause the disease.
      Clinical observations show a close relationship between PNH and aplastic anemia
      (AA), and it appears that the cause of the failure of normal hematopoiesis in AA
      enables the PNH clone to proliferate. Correction of the genetic defect in PNH
      cells by gene therapy may at first sight be an attractive proposition but the
      corrected "PNH" cells may be then be exposed to the insult causing bone marrow
      failure. This underscores the importance of a more complete understanding of the
      pathogenesis of the disease as a scientific foundation for gene therapy.

PMID- 9565158
TI  - Gene transfer for the eventual treatment of Fanconi's anemia.
AB  - Aplastic anemia can be either acquired or congenital. The paradigm for the
      congenital form is Fanconi's anemia (FA). FA is an autosomal recessive, genetic
      syndrome characterized by progressive bone marrow failure, developmental
      abnormalities, and a predisposition to malignancy. The clinical manifestations of
      FA are heterogeneous, but one common outcome in the majority of patients is the
      development of life-threatening hematologic disease. FA is thought to affect the
      hematopoietic stem cell, and the hematologic consequences of FA can be
      effectively treated by complete replacement of patient stem cells by those from a
      histocompatible donor. Unfortunately, allogeneic stem cell transplantation is
      currently limited to patients with an unaffected matched sibling donor.
      Transplantation from alternative donors, while successful in selected cases, is
      associated with a high risk of graft failure and must be carefully considered in
      terms of risk and benefit for each individual. For FA patients lacking an
      appropriate donor, new therapies need to be devised. This review summarizes both
      the scientific rationale and the progress of gene therapy strategies aimed at
      correcting the hematopoietic defect of FA.

PMID- 9565159
TI  - Recombinant factor IX for the treatment of hemophilia B. Introduction.

PMID- 9565160
TI  - The manufacturing process for recombinant factor IX.
AB  - Advances in recombinant DNA manufacturing technology have now made possible the
      production of a highly purified and active recombinant factor IX (rFIX) product.
      Recombinant factor IX was developed by (1) stable insertion of the genes for both
      factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance
      the capacity of cells to remove the amino-terminal propeptide from rFIX) into
      Chinese hamster ovary cells; (2) selection of a cell line that was capable of
      expressing high amounts of active rFIX while growing in bioreactors containing a
      completely defined culture medium that does not contain blood or plasma products;
      and (3) inclusion of four independent chromatography steps, none of which require
      monoclonal antibodies. Furthermore, rFIX has been extensively tested to
      demonstrate similarity to plasma-derived factor IX and has been shown to be a
      consistent, high-purity product. For example, a high-specific-activity product
      (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches
      from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and
      high-purity source of factor IX treatment for patients with hemophilia B.

PMID- 9565161
TI  - Biochemical characterization of recombinant factor IX.
AB  - Mature human factor IX is a 55,000-d glycoprotein with a modular domain structure
      and numerous posttranslational modifications. A recombinant form of human factor
      IX (rFIX) has been produced from a Chinese hamster ovary cell line that was
      engineered for high-level protein processing and expression. To ensure that the
      recombinant molecule contains the requisite structural and functional features of
      the plasma-derived form, rFIX was subjected to detailed biochemical and
      biophysical characterization. The laboratory studies showed that the
      posttranslational modifications and primary, secondary, and tertiary structures
      of rFIX were similar to those of plasma-derived factor IX (pdFIX). In addition,
      rFIX displayed a high degree of purity and a product release specification for
      specific activity that is > or = 200 IU/mg.

PMID- 9565162
TI  - The formulation of recombinant factor IX: stability, robustness, and convenience.
AB  - A lyophilized recombinant factor IX (rFIX) formulation has been developed that is
      stable and contains no preservatives. No blood or plasma products are used in the
      production or formulation of rFIX. The formulation contains 10 mmol/L histidine,
      0.26 mol/L glycine, 1% sucrose, and 0.005% polysorbate-80 (pH 6.8). Polysorbate
      80 acts as a protectant for the protein from freezing-induced damage (eg,
      aggregation). Sucrose provides protection to the protein in the freeze-dried
      state. Glycine provides for a high-quality cake morphology. Histidine provides
      optimal buffering stability at the desired pH and minimizes aggregate formation
      upon storage in the lyophilized state. This optimized combination of excipients
      provides a high degree of long-term stability, as demonstrated by a variety of
      analytical methods, including clotting assays, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing (IEF), size
      exclusion chromatography (SEC), peptide mapping, oligosaccharide fingerprinting,
      and reverse-phase high-performance liquid chromatography (HPLC). The rFIX product
      is easy to reconstitute and demonstrates excellent stability in solution after
      reconstitution.

PMID- 9565163
TI  - Viral safety of recombinant factor IX.
AB  - The viral safety of Chinese hamster ovary (CHO)-cell-based pharmaceuticals is
      well established. There have been more than 100 million infusions of CHO-derived
      pharmaceuticals without a single documented case of viral transmission. The
      recombinant factor IX (rFIX) process builds on this safety record by using a
      state-of-the-art multitiered approach to viral safety. This includes extensive
      testing of the CHO cells used to produce rFIX, routine viral monitoring of the
      cell culture production process, a manufacturing process and formulation that do
      not use blood or plasma products, and validation of the viral removal capacity of
      the purification process. The multifaceted viral safety program for rFIX has
      sufficient redundancy between approaches to compensate for potential limitations
      of any single safety measure. Together, the elements of the rFIX multitiered
      viral safety program offer patients and physicians a product that is inherently
      free of human blood-borne pathogens, including any risk of human immunodeficiency
      virus (HIV) hepatitis, parvovirus, and Creutzfeldt-Jakob disease (CJD).

PMID- 9565164
TI  - Preclinical studies of recombinant factor IX.
AB  - Recombinant factor IX (rFIX) has been extensively evaluated in preclinical
      studies. Dog model study of hemophilia B indicated that rFIX was as effective as
      a highly purified plasma-derived replacement factor in normalizing indices of
      hemostasis. Pharmacokinetic studies indicated a dose-proportional profile for
      rFIX. Pharmacokinetic/pharmacodynamic analysis showed that increases in the
      plasma concentration of rFIX following administration were closely correlated
      with measured factor IX activity in the plasma. Appropriate in vitro and in vivo
      toxicology studies have been performed to support the clinical use of rFIX for
      the treatment of hemophilia B. Finally, experiments in a model of thrombogenicity
      indicated that in animals rFIX has a low thrombogenic potential. The preclinical
      results provided a basis for proceeding with human clinical trials.

PMID- 9565166
TI  - Towards the equitably efficient and transparently decidable use of public funds
      in the deep blue millennium.
AB  - Health economists concerned about the efficiency and equity of health care
      provision have focused their attention and evaluations on programmes and
      interventions at a population or group level. Clinicians, including those seeking
      to improve the quality of care by making it more evidence-based, see their task
      as using their clinical judgment to make the best use of the resources available
      to them as a result of policy decisions The existence of significant incoherence
      between the two (or more) levels is increasingly recognized, but clinical
      guidelines, the only current response, are analytically inadequate to the task of
      reducing it. 'Clinical Guidance Trees', on the other hand, not only have the
      potential to bridge the policy-clinical gap but also provide the means by which
      public funds can be allocated to individual patients on the basis of a societally
      determined willingness to pay per incremental unit of benefit. This paper aims to
      stimulate debate about a system in which all public funds are allocated on the
      basis of patient specific cost-effectiveness analyses, conducted on the basis of
      sociopolitically determined parameters (including equity weightings), but
      individualized 'quality of life' measures. The system, seeking to maximize
      'equificiency', would do away with the increasingly unsustainable division
      between public and private sector provision and remove many expensive layers of
      health care decision making. While it would have many problems (including
      strategic behaviour various by parties), these need to be considered in the light
      of the problems of all alternative systems, including those of the status quo.

PMID- 9565165
TI  - Clinical evaluation of recombinant factor IX.
AB  - The pharmacokinetics, safety, and efficacy of recombinant factor IX (rFIX) have
      been evaluated in previously treated and untreated patients with hemophilia B. In
      a study of 56 previously treated patients, there was a total of 1,070
      hemorrhages, which required 1,514 infusions of rFIX. Of the 1,070 episodes, 80%
      resolved after a single rFIX infusion. The majority of the remaining episodes
      requiring more than 1 infusion were either major or complicated hemorrhages.
      Eighty-seven percent of the 1,514 infusions were rated by the physicians or
      patients as providing an excellent or good response. These results are consistent
      with the efficacy data from other hemophilia product clinical trials. rFIX has
      also been administered as bolus doses or by continuous infusion in conjunction
      with 13 surgical procedures. Estimated blood loss during and after surgery was as
      expected when compared with blood loss for similar procedures in patients without
      hemophilia, and 97% of the clinical responses during and after surgery were rated
      by physicians or patients as excellent or good. Pharmacokinetic comparison of
      rFIX with one plasma-derived product showed a statistically significant lower
      recovery (28% less) of rFIX. The half-lives between the two products were
      comparable. Common adverse events associated with rFIX treatment have been
      comparable to other factor IX products. As expected, there has been no evidence
      of viral transmission by rFIX.

PMID- 9565168
TI  - Discounting life-years: whither time preference?
AB  - If elicited time preferences are to be incorporated into economic evaluations,
      not only social but also individual preferences may be included. The view of this
      paper is that social intertemporal preferences should govern social intertemporal
      choices when prioritising between the saving of lives now or in the future.
      However, the present value of an individual's stream of future health benefits is
      a matter of private consumption and hence either individual time preferences or
      social interpersonal preferences could be applied when evaluating the value of
      extended life or improved quality of life. This paper shows that it is possible
      to incorporate both types of time preferences in an economic evaluation; using
      the individual time preference or the social interpersonal preference when
      discounting the remaining life expectancy and the social intertemporal time
      preference for discounting the health benefits from the time of the risk
      reduction to present time. Such a scenario could solve potential problems such as
      double discounting of QALYs, the paradox of intertemporal equity versus
      interpersonal equity, as well as include elements of quantity, risk and
      uncertainty which are otherwise ignored in evaluations of life-saving therapies.

PMID- 9565167
TI  - From competition to co-operation: new economic relationships in the National
      Health Service.
AB  - The Labour government has outlined its plans to 'replace' the competitive
      internal market with a more collaborative system based on partnership. Agreement
      amongst purchasers and providers is to be based on co-operation rather than
      competition. Longer term agreements covering periods of 3-5 years are to replace
      annual contracts within this new environment. The aim of this paper is to explore
      the potential economic implications of these policy changes by drawing on the
      economics of co-operation and the transaction costs approach to longer term
      contracting. Issues surrounding the role of trust in contractual relationships
      are explored and the relevance of experience and evidence from non-health care
      sectors is considered in the context of the NHS. It is concluded that both theory
      and empirical evidence suggest that co-operation and trust can play a central
      role in the efficient organisation of contractual arrangements in circumstances
      similar to those under which the NHS operates. However, we warn against the
      expectation that the policy changes will produce automatically the scale of
      benefits predicted by the Labour government, especially as they will have to find
      a way of extracting reasonable performance from providers under a system of
      collaboration and long term agreements. They may find they need to tread a fine
      line between competition and co-operation in order to reap the benefits of both.

PMID- 9565169
TI  - The cost-effectiveness of preference-based treatment allocation: the case of
      hysterectomy versus endometrial resection in the treatment of menorrhagia.
AB  - Typically, economic evaluation compares the costs and benefits of two or more
      interventions and seeks to identify the single superior option on the basis of
      relative cost-effectiveness. It is then anticipated that all patients will
      receive the more or most cost-effective option. This 'all or nothing' approach
      can be departed from when sub-groups of patient exist, defined on the basis of
      clinical or demographic characteristics which are considered to influence
      benefit, for whom an option is cost-effective whilst not being so for the
      population of patients as a whole. However, patients' preferences concerning the
      different process characteristics and outcomes of an intervention will also
      influence the benefit they derive from health care. This paper explores the
      concept of preference-based sub-group analysis in economic evaluation to assess
      the potential cost-effectiveness of using patients' preferences to determine
      treatment allocation. The clinical example used to explore these methods is the
      comparison of abdominal hysterectomy (AH) and transcervical resection of the
      endometrial (TCRE) for the treatment of menorrhagia.

PMID- 9565170
TI  - Bootstrap confidence intervals for cost-effectiveness ratios: some simulation
      results.
AB  - Recently, a number of papers have brought up the issue of how to make cost
      effectiveness (CE) studies stochastic, i.e. how to obtain confidence intervals
      for CE ratios. In this note we present a bootstrap procedure for estimating bias
      corrected confidence intervals for CE ratios. The bootstrap procedure is tested
      in a simulation study based on the assumptions made in a recent paper by Wakker
      and Klaassen in this journal. We test two variants of CE ratio bootstrap
      confidence intervals. The first is a bootstrap analogue of the parametric method
      proposed by Wakker and Klaassen which gives results similar to those obtained
      with the parametric method. However, computing bootstrap confidence intervals
      directly for the CE ratio produce results closer to the predetermined
      significance level.

PMID- 9565172
TI  - Health economics research and antitrust enforcement.
AB  - Antitrust analysis is typically very fact intensive, and enforcement outcomes
      always depend on the circumstances in particular markets. Nonetheless, there are
      issues of broad antitrust significance, and it is in these areas that health
      economics can make important contributions to enforcement policy. Indeed, health
      economics has already provided valuable guidance to antitrust enforcers in some
      areas. For example, when antitrust was first applied to hospital mergers in the
      early 1980s, it was sometimes argued that competition among hospitals was
      inherently perverse, inflating rather than restraining costs and prices. But
      studies of the 'California experience' with selective contracting and more
      careful assessment of the 'medical arms race' hypothesis provided persuasive
      support for applying standard antitrust presumptions to health care markets.
      Important new issues continue to arise. Some come from new challenges of standard
      presumptions in antitrust analysis, while others are attributable to changes in
      the rapidly evolving health care markets. These issues present new opportunities
      for health economists to provide guidance to antitrust enforcers and the courts.
      Guidance is most valuable when researchers recognize the key issues and
      understand the methodology with which antitrust analysts tackle competitive
      problems. The accompanying articles in this special issue are important
      contributions in these regards. In this article, we point to two recently
      litigated cases to highlight still other issues in which additional theoretical
      and empirical work by health care economists could be helpful in informing
      antitrust decision makers.

PMID- 9565171
TI  - Reduced uncertainty as a diagnostic benefit: an initial assessment of
      somatostatic receptor scintigraphy's value in detecting distant metastases of
      carcinoid liver tumours.
AB  - This paper employs classical concepts of diminishing marginal utility to
      demonstrate that risk-aversion can increase the perceived value of diagnostic
      procedures and thus raise optimum diagnostic expenditures. The theory is applied
      to a model in the spirit of Phelps and Mushlin's initial technology assessments.
      The specific evaluation is the cost-effectiveness of somatostatin receptor
      scintigraphy used to detect distant metastases of carcinoid liver tumours in a
      patient otherwise eligible for surgical resection of the liver. Data for the
      model are taken from published sources and financial databases, when available,
      and otherwise from a senior clinician's experience (LKK). The quantitative
      results indicate that receptor scintigraphy may have two beneficial impacts to
      risk-neutral individuals. First, it may reduce the combined costs of therapy and
      treatment because the diagnostic procedure costs less than the expected savings
      generated by avoiding inappropriate surgeries. Second, it may improve the
      patient's expected health-status-adjusted life years (HSALY) because the
      information allows physicians to better match treatment to the cancer's stage.
      Finally the paper demonstrates that risk aversion, as embodied in classical
      diminishing marginal utility applied to health status, can increase the value of
      the diagnostic tests and can lead the patient to choose a less beneficial
      treatment. An illustrative risk-averse utility function changed the optimum
      treatment from surgery to chemotherapy and increased scintigraphy's benefit by
      500%.

PMID- 9565173
TI  - Emerging issues in the antitrust definition of healthcare markets.
AB  - Managed care has shifted purchasing decisions from patients towards payers. While
      this shift has been associated with increased price competition in provider
      markets, we believe that it may enhance the potential for consumer injury from
      mergers in geographic markets previously considered immune to antitrust concerns
      (e.g. suburban components of large metropolitan areas). In addition, recent
      changes also increase concerns about mergers in product submarkets such as
      tertiary care.

PMID- 9565174
TI  - HMO mergers and Medicare: the antitrust issues.
AB  - This paper presents a theoretical framework to predict the effects that may arise
      from mergers in the rapidly-growing Medicare HMO market. We argue that mergers of
      large Medicare HMOs should be targeted for antitrust investigation because there
      are significant barriers into this market. The recent merger of PacifiCare and
      FHP is used to illustrate the potential antitrust issues raised by Medicare HMO
      mergers.

PMID- 9565175
TI  - Exclusive contracts between hospitals and physicians: the antitrust issues.
AB  - Exclusive contracts between hospitals and physicians are common. In most
      instances they raise no anticompetitive concerns. However, especially in rural
      markets, exclusive contracts may be used to foreclose actual and potential
      competitors and thereby decrease competition. The courts should weigh the
      benefits and costs of exclusive contracts in these areas.

PMID- 9565176
TI  - Physician networks and their implications for competition in health care markets.

PMID- 9565177
TI  - Pivotal issues in forensic psychiatry.
AB  - OBJECTIVE AND METHOD: This review examines the scope of forensic psychiatry with
      particular emphasis on its ethical and social implications. Some comparisons are
      made between the development of the subspecialty in Australasia and similar
      developments in the United Kingdom and North America, and the reasons for
      differences. RESULTS: There has been inadequate debate in Australasia about some
      of the ethical issues relating to the practice of forensic psychiatry.
      Furthermore, Australian forensic psychiatry in particular has been slow to
      develop comprehensive and integrated services compared to other jurisdictions,
      and remains predominantly an assessment-based activity with primacy of the expert
      witness. CONCLUSIONS: Australasian psychiatry faces significant problems with
      respect to maldistribution of services. Governments are becoming more radical in
      their attempts to address this maldistribution and this has ethical implications
      for the profession itself and the practice of forensic psychiatry. Greater
      emphasis on the development of integrated and community-based forensic services,
      with leadership being provided by the profession itself, may deflect some of the
      present criticism, thereby allowing the subspecialty to more fully mature and
      develop with the approach of the new millennium.

PMID- 9565178
TI  - Access to methods of suicide: what impact?
AB  - OBJECTIVE: The aim of this paper is to explore the conceptual basis of limiting
      access to potential methods of suicide as a public health measure. METHOD: A
      review of the literature was conducted. RESULTS: Both physical availability and
      sociocultural acceptability are important determinants of choice. There is
      considerable evidence of an association between method availability and method
      specific suicide rates. There is also evidence that restriction of method
      availability is often associated with a reduction in method specific suicide
      rates. There is some evidence that restrictions on method availability under
      certain conditions may reduce overall suicide rates. CONCLUSIONS: Suicide methods
      employed by young Australians are changing, with a disturbing rise in frequency
      of hanging and car exhaust suicides slightly offset by a decline in firearm
      suicides. Opportunities exist for further reducing firearm suicides and
      addressing exhaust suicides by practical measures. There are also obvious options
      for changing prescribing practices with respect to more lethal medications (e.g.
      tricyclic antidepressants). However, the rise in hanging seems problematic from
      this perspective and in need of ecological study.

PMID- 9565179
TI  - Recovery from post-earthquake psychological morbidity: who suffers and who
      recovers?
AB  - OBJECTIVE: We sought to identify the psychosocial characteristics of high
      earthquake exposure subjects that were associated with the development of post
      disaster morbidity and with recovery. METHOD: Data reported are from 515
      participants in a longitudinal study of the psychosocial effects of the 1989
      Newcastle (Australia) earthquake. Subjects were allocated to three subgroups (low
      morbidity; recovered; and persistent morbidity) on the basis of their Impact of
      Event Scale scores across the four phases of the study. Differences between these
      subgroups were examined on a broad range of variables. RESULTS: Several
      background, dispositional, coping style and exposure-related factors
      characterised those who developed psychological morbidity, only a small subset of
      which differentiated between those who recovered and those with persistent
      morbidity. CONCLUSIONS: Post-earthquake morbidity persists longer in those who
      are older, have a history of emotional problems, have higher neuroticism, use
      more neurotic defenses, and report higher levels of post-disaster life events.

PMID- 9565180
TI  - Risk factors for posttraumatic stress disorder in Australian Vietnam veterans.
AB  - OBJECTIVE: The aims of this paper are to determine the risk factors for combat
      related posttraumatic stress disorder (PTSD) and to examine the relative
      contribution of pre-military factors, pre-trauma psychiatric diagnoses, military
      factors such as combat posting, and combat and casualty stress exposure. METHOD:
      An epidemiological cohort study using standardised psychiatric, social and health
      interviews was undertaken with a national random sample of male Australian Army
      Vietnam veterans. Multivariate logistic regression was used to examine the
      relative contribution of factors derived from interview and from military records
      in four categories: pre-enlistment circumstances including home life, education,
      major life stress; pre-Vietnam psychiatric diagnoses; military experiences before
      and during Vietnam; and combat and stress experiences. RESULTS: Of the 128 data
      items examined, significant associations were found for 39, in addition to combat
      stress. Pre-enlistment items accounted for about 3% of the deviance towards PTSD
      diagnosis, pre-enlistment psychiatric diagnosis about 13%, military variables
      about 7% and combat stress about 18%; all factors together accounted for 42%.
      CONCLUSIONS: The results confirm that pre-military and military variables make
      only a small but significant contribution to PTSD either alone or after
      controlling for combat stress; that psychiatric diagnoses of depression,
      dysthymia and agoraphobia make strong contributions to PTSD; but that combat
      stress makes the largest contribution even after controlling for the effects of
      other variables. Psychiatric diagnoses and combat stress appear to be independent
      in their effects on PTSD.

PMID- 9565181
TI  - Posttraumatic stress disorder and comorbidity in Australian Vietnam veterans:
      risk factors, chronicity and combat.
AB  - OBJECTIVE: The objective of this study was to examine the relationship between
      combat-related posttraumatic stress disorder (PTSD) and comorbid DSM-III-R
      psychiatric diagnoses to determine commonalities in risk factors, relative onsets
      and the role of combat exposure. METHOD: An epidemiological cohort study using
      standardised psychiatric, social and health interviews was undertaken with a
      national random sample of male Australian Army Vietnam veterans. Interviews and
      searches of military records yielded risk factors for PTSD, which were examined
      for association with each psychiatric diagnosis. Relative onsets of PTSD and each
      Diagnostic Interview Schedule diagnosis were compared. Comorbidity odds ratios
      were adjusted for combat exposure effects using logistic regression, and the
      relation between each diagnosis and combat was assessed after controlling for
      PTSD. RESULTS: Commonality of risk factor profile was evident for several
      diagnoses, and for many their onset preceded PTSD onset. Combat was independently
      related to only a few diagnoses after controlling for PTSD, and PTSD remained
      strongly associated with several conditions after controlling for combat
      exposure. CONCLUSIONS: The analysis suggests that the disorders that may
      constitute risk factors or vulnerabilities for PTSD comprise depression and
      dysthymia, antisocial personality disorder, agoraphobia and simple phobia, while
      those that may be consequent on PTSD are panic and generalised anxiety disorder,
      drug use disorders and somatoform pain disorder. Alcohol and drug use disorders
      and social phobia may have a mixed aetiology, while obsessive-compulsive disorder
      may be serendipitously related to PTSD through an association with risk of
      combat. Gambling disorder is unrelated.

PMID- 9565183
TI  - Neuroleptic management of schizophrenia: a survey and commentary on Australian
      psychiatric practice.
AB  - OBJECTIVE: We seek to assess Australian psychiatrists' views and practices
      concerning provision of neuroleptic medication to patients with schizophrenia,
      and to determine whether such management strategies are likely to have changed
      over time and the extent to which they correspond to published treatment
      guidelines. METHOD: A sample of 139 psychiatrists based in three Australian
      capital cities was derived, with respondents completing a brief questionnaire by
      choosing from a limited-option answer set. Co-authors of this paper comment on
      the extent to which responses are in line with contemporary recommendations
      driven by experts or empirical studies. RESULTS: Overall, survey findings
      indicate that there has been considerable change in clinical practice over the
      last decade and provide some estimate of the extent to which Australian
      management practices are congruent with contemporary recommendations. We identify
      a number of issues of concern (more in relation to dose levels of neuroleptic
      medication rather than treatment duration) revealed by survey data and make
      recommendations for addressing a number of practical clinical issues.
      CONCLUSIONS: As this report focuses on central issues involved in managing
      schizophrenia, and integrates a number of treatment guidelines, we suggest that
      it should be of assistance for practice review by clinicians.

PMID- 9565182
TI  - Optimal treatment strategies to enhance recovery from schizophrenia.
AB  - OBJECTIVE: The aim of this paper is to examine the base for integrating
      biomedical, psychological and social strategies in the management of
      schizophrenia. METHOD: A review of the literature on schizophrenia with
      particular emphasis in management considerations. RESULTS: Effective treatment
      components include psychoeducation, medication strategies, career-based stress
      management training, community-based intensive treatment, living skills training,
      and specific drug and cognitive-behavioural strategies for residual symptoms.
      CONCLUSIONS: Treatment for schizophrenia is best provided by integrating the
      various and specific psychosocial intervention strategies in addition to the
      optimal use of medication. Methods for implementing these strategies in
      outpatient settings include the use of a comprehensive assessment and treatment
      plan, the training of mental health professionals, and periodic review with
      assessment packages.

PMID- 9565184
TI  - How effective is lithium in the prevention of relapse in bipolar disorder? A
      prospective naturalistic follow-up study.
AB  - OBJECTIVE: The effectiveness of lithium in preventing recurrences of bipolar
      disorder was examined prospectively for 2 years in two representative samples of
      bipolar I patients being treated in a comprehensive program following recommended
      guidelines. METHOD: One hundred and twenty patients were recruited from
      consecutive admissions to two catchment area psychiatric services (one in the
      United Kingdom, the other in New Zealand). They were seen at 3-monthly intervals
      by a member of the research team. Treatment was adjusted according to clinical
      needs. RESULTS: Overall, two-thirds of the patients had a recurrence. Of the 57
      on lithium as sole treatment, 39 (68%) had a further episode; 17 after stopping
      lithium. The 42 on other mood stabilisers and/or an antipsychotic, with or
      without lithium, did no better. By contrast, only eight (38%) of the 21 who were
      taking no prophylactic medication had a recurrence. CONCLUSIONS: Lithium is much
      less effective in clinical practice than would be expected from clinical trial
      results. A major reason for this is poor compliance. Alternative treatment
      strategies are needed to improve the outcome for bipolar disorder patients.

PMID- 9565185
TI  - The prevalence of comorbid anxiety in schizophrenia, schizoaffective disorder and
      bipolar disorder.
AB  - OBJECTIVE: The aim of this study to determine the prevalence of anxiety disorders
      in publically treated psychiatric inpatients with a DSM-IV diagnosis of
      schizophrenia, schizoaffective disorder or bipolar disorder. METHOD: Using the
      Structured Clinical Interview for DSM-III-R (SCID), 100 consecutive inpatients
      with a psychotic disorder were examined for the presence or absence of an anxiety
      disorder. Questionnaire measures of phobias, obsessive-compulsive and general
      anxiety symptoms were also applied. RESULTS: The prevalences of social phobia
      (17%), obsessive-compulsive disorder (13%) and generalised anxiety disorder in
      schizophrenia were relatively high, as were prevalences of obsessive-compulsive
      (30%) and panic disorder (15%) in bipolar disorder. The proportion of subjects
      with an anxiety disorder (43-45%) was almost identical across the three
      psychoses, with some evidence of gender differences. Although self-ratings of
      overall psychiatric symptoms were significantly elevated in those with anxiety
      disorders, hospital admission rates were not. CONCLUSIONS: Almost none of those
      with anxiety disorders were being treated for them, primarily because the
      severity of the acute psychotic illness required full diagnostic and therapeutic
      attention. Patients were generally discharged as soon as their psychotic episode
      was resolved, with little recognition of the presence of an anxiety disorder.
      Given that anxiety disorders are relatively responsive to treatment, greater
      awareness of their comorbidity with psychosis should yield worthwhile clinical
      benefits.

PMID- 9565186
TI  - Confirmation of the diagnosis of schizophrenia after death using DSM-IV: a
      Victorian experience.
AB  - OBJECTIVE: This study examines the reliability of antemortem diagnoses of
      schizophrenia using DSM-IV criteria. METHOD: The case histories of 83 subjects
      with a provisional diagnosis of schizophrenia at autopsy were retrospectively
      reviewed using a semi-structured chart review and application of DSM-IV criteria.
      Agreement between antemortem and postmortem diagnoses of schizophrenia was
      examined, as well as the concordance between DSM-IV diagnoses and previously
      obtained diagnoses using DSM-III-R and ICD-10 criteria for schizophrenia.
      RESULTS: According to DSM-IV, 30.1% of cases did not have schizophrenia, compared
      to 36.1% using DSM-III-R criteria and 51.8% of cases using ICD-10 criteria.
      Concordance between DSM-IV and DSM-III-R diagnoses of schizophrenia was excellent
      (kappa = 0.81), but only fair between DSM-IV and ICD-10 (kappa = 0.57). Of the
      cases that did not meet the formal criteria for schizophrenia, the majority were
      reassigned diagnoses of schizoaffective disorder and affective disorder.
      CONCLUSIONS: The use of human brain tissue in postmortem studies of schizophrenia
      must be linked to standardised diagnostic assessment procedures. Diagnoses can be
      upgraded with the development of new criteria, providing sufficient clinical data
      is available in case histories.

PMID- 9565187
TI  - Anthropometry and adiposity in a group of people with chronic mental illness.
AB  - OBJECTIVE: The prevalence of excess body weight has been reported as two to four
      times greater in the chronic mentally ill than in the general population.
      However, there has been a paucity of body composition research with this
      population. The purpose of this study was to compare with population data the
      prevalence and distribution of body fat in a group of chronic mentally ill
      individuals. METHOD: An anthropometric profile consisting of height, weight,
      waist and hip girths was completed on 29 males and 23 females. RESULTS:
      Consistent with other groups with excess adiposity, measures of skinfold
      thickness were generally unreliable. The biceps was the only site where a
      reliable skinfold measure was possible in all subjects. More than half of the
      males and three-quarters of the females had a waist circumference in excess of
      100 cm. CONCLUSIONS: There were significantly higher levels of relative body
      weight and excess abdominal adiposity in the study group compared with the wider
      population. A brief anthropometric protocol of waist and hip girths and biceps
      skinfold in addition to height and weight, rather than the use of weight alone as
      an indicator of adiposity, is recommended.

PMID- 9565188
TI  - Nutrition and obesity in the chronic mentally ill.
AB  - OBJECTIVE: The aim of this study was to determine the need for nutrition
      intervention in a group of people living in mental health residential houses in
      the Northern Sydney Area. METHOD: A nutrition assessment was conducted by the
      researcher using a face-to-face interview with mental health residents and a
      survey on medical background completed by case managers. RESULTS: The prevalence
      of overweight and obesity was significantly greater than that reported for the
      general population. Respondents also had a significantly higher prevalence of
      abdominal obesity than the general population. No respondent met the minimum core
      food group requirements as outlined in the 12345+ Food and Nutrition Plan.
      CONCLUSIONS: The needs assessment has shown that nutrition promotion is required
      in this group. The task ahead is to motivate the group to change their food and
      nutrition behaviours, where many barriers to a healthy lifestyle exist.

PMID- 9565189
TI  - A critical review of the biopsychosocial model.
AB  - OBJECTIVE: The aim of this review is to provide an analysis of the epistemic
      status of the biopsychosocial model. METHOD: A critical comparison of the
      biopsychosocial model with the general concept of models. RESULTS: In its present
      form, the biopsychosocial model is so seriously flawed that its continued use in
      psychiatry is not justified. CONCLUSION: Further development of theory-based
      models in psychiatry is urgently needed.

PMID- 9565190
TI  - Directions of aetiologic research on attention deficit hyperactivity disorder.
AB  - OBJECTIVE: The aim of this paper is to review and integrate recent literature on
      aetiological factors that have been postulated for attention deficit
      hyperactivity disorder (ADHD). METHOD: Recent studies relating to perinatal brain
      damage, intra-uterine toxic effects, neurochemical, brain imaging and genetic
      studies are reviewed, and those considered most significant are discussed. Where
      possible, recent findings are integrated and directions of future research are
      suggested. Clinical implications are briefly discussed. RESULTS: Perinatal
      studies indicate that children with a birth weight under 750 g may be
      disadvantaged for attentional skills. Magnetic resonance imaging (MRI) and steady
      state visually evoked potential studies show differences in prefrontal, caudate
      and parietal areas in ADHD children, suggesting right hemispheric dysfunction.
      Functional MRI studies hold promise in further elucidating attentional systems in
      the central nervous system that are involved in ADHD. Genetic studies suggest
      genes related to dopaminergic systems may be important. CONCLUSIONS: Recent
      research on ADHD has made considerable advances, particularly in the areas of
      brain imaging and genetic studies. Genetic studies should provide further
      aetiological understandings of ADHD, leading to more targeted treatments.

PMID- 9565192
TI  - The effectiveness of group psychological intervention in enhancing perceptions of
      control following spinal cord injury.
AB  - OBJECTIVE: This research investigated the effects of a structured psychological
      intervention, delivered during hospital rehabilitation, on the perceptions of
      control in people with spinal cord injury (SCI). METHOD: A longitudinal study was
      designed to assess perceptions of control (using an objective measure of locus of
      control) in SCI persons who participated in specialised group cognitive
      behavioural therapy (CBT) during hospital rehabilitation. The treatment SCI
      group's responses on locus of control were compared with a control group of SCI
      persons who only received traditional rehabilitation services during their
      hospitalisation. RESULTS AND CONCLUSIONS: Mean locus of control scores were not
      high (i.e. external) for both groups and there were no overall group differences
      on locus of control responses across time in comparison to the control group.
      However, subjects in both groups who initially perceived life as externally
      controlled were extracted to form subgroups. The members of the subgroup who
      received CBT were significantly more likely to feel in control of themselves 2
      years post injury compared to similar persons in the control group. Furthermore,
      an external locus of control was significantly but mildly associated with
      depressive mood 2 years after the injury. This research suggests that the
      provision of a structured psychological program in the rehabilitation stage will
      be beneficial for many SCI persons who feel that they have little control over
      their lives.

PMID- 9565191
TI  - An aetiological model of non-melancholic depression: study design and validity of
      the measures.
AB  - OBJECTIVE: The aim of this paper is to describe an approach to sub-typing non
      melancholic depression and to determine which raters from a variety of
      backgrounds provided the most valid information on study variables. METHOD: A
      sample of non-melancholic depressed patients is described. Multiple raters (i.e.
      patients, psychiatrists, referrers and corroborative witnesses) completed
      measures of the patient's trait anxiety levels, severity of recent life event
      stressors and personality functioning. RESULTS: The study and representative data
      are reported. Congruence between several measures employed indicated that
      psychiatrist rating of disordered personality was superior to corroborative
      witness report. Assessment of anxiety traits indicated reasonable agreement
      between referrers and corroborative witnesses but poor agreement between those
      ratings and interview-elicited ratings. There were also discrepancies in
      quantifying 'severity' of life event stress, with patients and their
      corroborative witnesses rating such events as more severe than either the
      interviewing psychiatrist or psychiatrists involved in consensus rating sessions.
      Importantly, the psychiatrists' capacity to quantify the relative contribution of
      disordered personality, anxiety and life-event stress to the particular
      depressive episode was supported. CONCLUSIONS: Results indicate some of the
      difficulties in operationalising determinants that may contribute to and sub-type
      the non-melancholic depressions, and demonstrate the advantages of using a range
      of rating strategies and raters. In this study, psychiatrist-generated judgements
      are clearly favoured, although the advantages of also assessing trait anxiety and
      life-event stress impact by self-report strategies are conceded. Some techniques
      for estimating the contribution of disordered personality function, anxiety and
      life-event stress are offered for both their research and their clinical utility.

PMID- 9565193
TI  - Neuroplasticity and psychiatry.
AB  - OBJECTIVE: There is increasing concern that the course of psychiatric disorders
      may be affected by parameters such as the duration and intensity of symptoms of
      initial episodes of illness. As this indicates that abnormal function produces
      long-term changes within the brain, a review of the neuroscience literature
      regarding neuroplasticity is warranted. METHOD: This article is a selective
      review, focusing in particular on results obtained from physiological experiments
      assessing plasticity within the mammalian neocortex. The possible relevance of
      results to psychiatry is discussed. RESULTS: While the most dramatic examples of
      neuroplasticity occur during a critical period of neural development,
      neuroplasticity can also occur in adult neocortex. Neuroplasticity appears to be
      activity-dependent: synaptic pathways that are intensively used may become
      strengthened, and conversely, there may be depression of transmission in
      infrequently used pathways. CONCLUSIONS: Results from neurophysiological
      experiments lend support to the clinical observation that the intensity and
      duration of a psychiatric disorder may adversely alter its long-term course.
      Rapid aggressive treatment may prevent this from occurring. While pharmacotherapy
      may reduce the duration and severity of symptoms, it may also have an
      independent, as yet unknown, effect on neuroplasticity.

PMID- 9565194
TI  - Dysmorphic concern: prevalence and associations with clinical variables.
AB  - OBJECTIVE: The aim of this paper is to describe the development of a
      questionnaire, the Dysmorphic Concern Questionnaire (DCQ), for the assessment of
      dysmorphic concern, and to establish correlations with clinical variables.
      METHOD: Consecutive admissions to a psychiatric hospital were surveyed. RESULTS:
      The DCQ showed good internal consistency, with most of the variance being
      explained by a single factor. Strong correlations with distress and work and
      social impairment lend face validity to the questionnaire. Dysmorphic concern was
      not significantly influenced by the patient's age, sex or diagnosis. In terms of
      specific psychotic symptoms, there were weak positive correlations with thought
      interference and persecutory ideation. However, the strongest correlations were
      with depressed mood, according to the Beck Depression Inventory (BDI) but not the
      Montgomery Asberg Depression Rating Scale; the discrepancy was largely accounted
      for by the 'cognitive' depressive items on the BDI. In terms of objective
      assessment of dysmorphic features, ratings on the Waldrop scale for minor
      physical anomalies showed no correlation with concern expressed by the patient.
      CONCLUSIONS: The strong correlation with depressive cognitions suggests that
      dysmorphic concern is often a reflection of a depressive cognitive set rather
      than being a diagnosis in itself.

PMID- 9565195
TI  - Single dose pharmacokinetic study of lithium in Taiwanese/Chinese bipolar
      patients.
AB  - OBJECTIVE: The purpose of this study is to investigate the single dose
      pharmacokinetics of lithium in Taiwanese/Chinese bipolar patients for future
      interracial comparisons. METHOD: Eight bipolar patients took 900 mg of lithium
      carbonate after overnight fasting. Blood samples of 5 mL were taken after 15 min,
      30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 7 h, 9 h, 15 h, 25 h and 31 h after dosing.
      The computer programs CSTRIP and PCNONLIN were used for pharmacokinetic analysis.
      RESULTS: The pharmacokinetic parameters obtained were as follows: Cmax, 0.970 +/-
      0.170 (SD) mmol/L; Tmax, 1.59 +/- 0.78 h; AUC31 h = 548.9 +/- 135.4 mmol x m/L;
      AUC to infinity = 722.6 +/- 262.7 mmol x m/L; beta-half-life = 16.3 +/- 7.18 h;
      kappa-half-life = 0.613 +/- 0.442 h; Cl(oral) = 1.13 +/- 0.39 mL/min/kg; Vd/F =
      1.43 +/- 0.387 L/kg. Most of the pharmacokinetic parameters were within the
      ranges reported in investigations of Caucasian subjects. CONCLUSIONS: This study
      showed that racial differences in lithium pharmacokinetics might not exist. We
      suggest that methodological designs, including method of blood sampling,
      measurement of lithium, and pharmacokinetic and statistical calculations, be
      standardised if future cross-ethnic comparisons are to be conducted.

PMID- 9565196
TI  - Season of birth and schizophrenia in Tasmania.

PMID- 9565197
TI  - Beyond adolescent psychiatry: the logic of a youth mental health model.

PMID- 9565198
TI  - Longer than expected course of transcranial magnetic stimulation.

PMID- 9565199
TI  - Comment on psychiatry: an impossible profession?

PMID- 9565200
TI  - The bowerbird symptom.

PMID- 9565201
TI  - Bipolar affective disorder and thalassaemia minor.

PMID- 9565202
TI  - Intravenous sedation of involuntary psychiatric patients in New South Wales.

PMID- 9565203
TI  - Psychosocial histories, social environment, and HIV risk behaviors of injection
      and noninjection drug using homeless youths.
AB  - Injection drug use is a common risk behavior for HIV infection among homeless,
      runaway and street youths. However, the psychosocial histories and current social
      environment of these youths are not well understood. The authors recruited 186
      homeless, runaway and street youths using systematic street-based sampling
      methods, and assessed psychosocial histories, current daily activities, and
      sexual and drug-related risk behaviors using qualitative and quantitative
      techniques. Youths reported high lifetime rates of injection drug use (45%),
      recent drug and alcohol use (100%), and current homelessness (84%). Injection
      drug using youths were more likely than noninjection drug using youths to report
      traumatic psychosocial histories, including parental substance use and forced
      institutionalization, use of alcohol and other noninjection drugs, a history of
      survival sex, and the use of squats or abandoned buildings as shelter. These
      findings underscore the need for multifaceted service and prevention programs to
      address the varied needs of these high-risk youths.

PMID- 9565204
TI  - Profiles of heroin addicts in different treatment conditions and in the
      community.
AB  - This article describes profiles of heroin addicts in three types of treatment
      (methadone, detox and therapeutic community) and those not in treatment in the
      local community. The profiles are based on data at item-level of the revised
      Addiction Severity Index. In total, 310 heroin addicts were interviewed. The
      results show that on the one hand the community group and the methadone group are
      roughly comparable, and on the other hand the detox and therapeutic community
      groups have similar characteristics. The latter groups report significantly more
      psychological and social problems. The community group mentions the fewest
      problems with drug use and more illegal activities in the past month. The results
      indicate that large differences exist between the groups in psychosocial
      problems. Furthermore, they indicate that the methadone group has no specific
      pattern of problems. Two important groups outside treatment are identified with
      respect to matching: addicts under 25 years old and addicts with a non-Dutch
      cultural background.

PMID- 9565205
TI  - Estimation of the prevalence of injection drug use in greater Boston in 1993.
AB  - This article is a report on different methods of estimation of the number of
      injection drug users (IDUs) in the Boston standard metropolitan statistical area
      (SMSA) in 1993. Because the sharing of needles is a means of transmission for
      HIV, an estimate of the prevalence of injection drug use is essential for
      acquired immunodeficiency syndrome (AIDS) prevention programs. The data for this
      study come from the Massachusetts Department of Public Health Bureau of Substance
      Abuse, the Massachusetts AIDS Surveillance Unit, the Drug Abuse Warning Network
      (DAWN), the National Household Survey on Drug Abuse: Population Estimates 1993,
      and the Massachusetts State Police Crime Reporting Unit. The estimates in this
      study can be assessed with regard to the different time frames that are involved,
      noting that some estimates are useful only to establish upper or lower bounds.
      The estimate that best meshes with the findings of this report is that there were
      between 13,500-16,500 injection drug users in greater Boston and 45,000-60,000
      IDUs in Massachusetts in 1993.

PMID- 9565206
TI  - A Russian-American approach to the treatment of alcoholism in Russia: preliminary
      results.
AB  - The enormous cost of alcoholism to Russian society threatens to block the current
      transition towards a functioning democracy. The authors describe the introduction
      of a 12-Step based psychotherapeutic treatment approach at the Recovery Treatment
      Center in Moscow. This program is the result of extensive collaboration between
      American addiction experts, Russian psychologists and recovering alcoholics since
      1990. Preliminary outcome data and analysis of in-depth interviews with fifteen
      patients who successfully completed treatment at this center suggest this
      approach can be successfully introduced into Russia in a way that has special
      relevance to the current democratic transformation in the society at large.

PMID- 9565207
TI  - Alcohol-related homicides committed by women.
AB  - In this paper we use data derived from interviews with female homicide offenders
      either incarcerated or on parole in New York to examine those cases (N=35) that
      the respondents believed were related to their use of alcohol at the time of the
      homicide. We found four basic types of these homicides based on victim-offender
      relationships and the circumstances of the incidents. Women who committed each
      type of alcohol-related homicide reported a variety of motives for committing
      these acts. We also found that there were similarities and differences between
      the types, not only in terms of the kinds of motives reported but also in terms
      of the extent to which planning was involved. Likewise, there were similarities
      and differences between the different types of homicides regarding the type and
      amount of alcohol and other drugs used by respondents on the day of the incident,
      and regarding respondents' perceptions of the alcohol-relatedness of the events.
      The implications of our findings are discussed.

PMID- 9565208
TI  - Patterns of alcohol use among adolescents living in Porto Alegre, Brazil.
AB  - A cross-sectional household survey was used to assess patterns of alcohol
      experimentation and consumption among Brazilian adolescents, stratified by age
      and sex. Trained interviewers administered a standardized questionnaire to 950
      subjects, ages 10 to 18, which examined such things as age of first alcohol use,
      situational aspects of consumption, amounts ingested and use among peers.
      Lifetime prevalence of alcohol use was high (71.5%), especially in the older
      teens (94.4%). The mean age of first use was 10 years, and consumption of all
      types of alcohol, including hard liquor, was common. Alcohol use typically began
      in the home, at family celebrations and social occasions, and progressively
      evolved to street drinking with peers. This pattern was most evident in males,
      who reported a larger volume of alcohol consumption per episode, when compared to
      females. The total amount of alcohol consumption reported for all ages is very
      high and may be due to permissive cultural views of alcohol. Age and gender play
      an important role in the evolution of drinking, with male adolescents being
      exposed to higher concentrations of alcohol and at younger ages than females, who
      seem to have a more conservative attitude toward excessive drinking. Subjects
      considered these practices normal, with no concern about the illegality of such
      behaviors.

PMID- 9565209
TI  - Male drug abuse, criminality and subcultural affiliation in a career perspective.
AB  - Degree of connection to the criminal underworld was the basis for typologic
      research on 698 male drug abusers; interviews as well as official records were
      used. Four types were distinguished: The addicted criminals seemed to resemble
      the groups dominant in Sweden from the 1950s to the 1970s. An early crime debut
      and criminal offenses in youthful years characterized their deviant careers.
      Drugs and criminal activities coexisted with an often very high intake of alcohol
      and the most difficult childhood and adolescence conditions compared to the other
      types. The criminal addicts had fewer recorded acts of juvenile delinquency.
      Their drug abuse was severe and occurred later in life, as criminality did, but
      tended to accelerate very rapidly. Their subcultural affiliation was probably as
      strong as that of the addicted criminals. A large group called low-crime addicts
      had a weak subgroup affiliation. The "normal" abuse pattern, with cannabis as the
      first substance used and a gradual shift to more severe opioid and CNS stimulant
      abuse, was most true of this type. Probably the drug abuse played a role in the
      development of the criminal pattern. Emotionally unstable addicts with little or
      no criminality had the best education, job situation and social relations.
      Multiple drug abuse and abuse of legal drugs were common. Mental ill-health was
      characteristic for this group. The results show that drug abusers in Sweden
      cannot be seen as a homogeneous group of individuals, that they do not commit
      crimes only in order to finance their habit, and that the history of narcotics
      use in Sweden, with its strong connection to a criminal subculture, is highly
      relevant to this sample.

PMID- 9565210
TI  - Barriers to effective drug abuse prevention: the role of authoritarian ideology.
AB  - The relationships between authoritarian ideology and attitudes and beliefs about
      illegal drugs, the War on Drugs, and prevention strategies were investigated
      among 353 university faculty, administrators, and students. A confidential mail
      survey assessed five variables: right-wing authoritarianism, attitude toward drug
      legalization, attitude toward drug decriminalization, belief regarding the
      controlled use of illegal drugs, and the tendency to endorse a "just say no"
      approach to substance abuse prevention. Multivariate analyses revealed that
      highly authoritarian participants were significantly more opposed to both drug
      legalization and drug decriminalization than less authoritarian participants.
      Only nonauthoritarian participants favored decriminalization, though they did not
      favor legalization. Compared to those scoring lower on authoritarianism, higher
      scoring authoritarian participants held significantly more dichotomous beliefs
      about illegal drugs (i.e., that abstinence or compulsive drug abuse are the only
      possibilities related to involvement with illegal drugs). They were also less
      likely to recommend to potential drug users that they consider following
      guidelines for their use that may potentially function as protective factors
      against drug abuse, preferring instead to endorse the slogan "just say no to
      drugs." Comparisons between groups revealed that students scored significantly
      higher on authoritarianism and demonstrated significantly greater opposition to
      drug decriminalization than did faculty and administrators.

PMID- 9565211
TI  - Using peer, self, and counselor ratings to evaluate treatment progress.
AB  - It is generally recognized that the evaluation of treatment progress requires
      multiple methods of assessment. To provide a basis for supplementing existing
      measures, the current study investigated the use of a peer rating methodology for
      evaluating the treatment progress of 381 probationers admitted to a four-month
      residential drug abuse facility. Self ratings of "working the program" (i.e.,
      conscientiously participating in treatment) were compared with ratings by peers
      in the program and with ratings by counselors. Peer and counselor ratings were
      more highly correlated with each other than with client self ratings. Peer as
      well as self ratings detected differences between enhanced and standard
      counseling, and were related to individual difference measures known to be
      associated with treatment progress. In addition, peer midterm ratings of "working
      the program" were related to both self and counselor ratings of clients' endterm
      participation, and counselor ratings of the likelihood of remaining clean and
      sober. These findings support the use of peer ratings as additional indicators of
      treatment progress.

PMID- 9565212
TI  - Attitudes toward methadone maintenance: implications for HIV prevention.
AB  - Attitudes of opioid users toward methadone maintenance were studied using semi
      structured field interviews. One hundred and sixty-one heroin and speedball users
      in San Antonio, Texas, were interviewed between 1989 and 1992. Users were
      classified according to whether or not they had ever been on methadone
      maintenance. Opioid users who had never been on methadone maintenance were more
      likely to express a negative attitude toward methadone maintenance than users who
      had been on it (50% versus 30%). Sources of negative attitudes fell into the
      following categories: (1) general societal disapproval of addictive drugs,
      including methadone; (2) prior experience with 12 Step groups or abstinence-based
      treatment programs; (3) previous forced rapid detoxification from methadone in
      jail; and (4) observation of methadone maintained peers who continued to use
      drugs. Very few respondents reported adverse effects from methadone itself as a
      source of negative attitudes. Sources of positive attitudes included: (1) prior
      successful treatment with methadone; and (2) observation of methadone patients
      who stopped using drugs.

PMID- 9565213
TI  - Reply to Lilienfeld: why alcoholism is a disease.
AB  - Lilienfeld's attack on my conceptual examination of the disease concept of
      alcoholism suffers from erroneous interpretations, fallacious reasoning, and a
      lack of familiarity with relevant alcoholism research. He offers an alternative
      nominalist interpretation of the disease concept of alcoholism based on a fuzzy
      boundary between disease and wellness. He fails to recognize that the basic issue
      between nominalist and realist accounts of a lower-order concept such as
      alcoholism is the presence or absence of general principles that may account for
      the observed signs and symptoms characterizing a specific disease entity, not
      fuzzy boundaries between higher-order categories. Extensive evidence (which
      Lilienfeld ignores) of biological bases for the pathognomic signs and symptoms of
      alcoholism, particularly loss of control, demonstrates that the disease concept
      of alcoholism refers to a disease entity that has a biological basis. It is not a
      "mental construct."

PMID- 9565214
TI  - Violence, drugs, and prohibition.

PMID- 9565215
TI  - Premedication for neonatal intubation.
AB  - The incidence of complications was recorded for 269 consecutive neonatal
      endotracheal intubations after instituting a routine policy of premedication. Two
      hundred and fifty-three of the intubations were premedicated with a combination
      of atropine, fentanyl and succinylcholine, 194 were without incident, 28 required
      two attempts, 22 required more than two attempts, and 9 required a second attempt
      with a smaller endotracheal tube. All infants were successfully intubated. We
      conclude that a policy of routine neonatal premedication for intubation is safe,
      feasible, and humane.

PMID- 9565216
TI  - Pulmonary mechanics of normal very-low-birth-weight infants at 40 weeks
      postconception: a comparison with normal term infants.
AB  - We evaluated pulmonary function status in healthy, nonventilated very-low-birth
      weight (VLBW) infants at 40 weeks postconception because little is known about
      the pulmonary function status of these infants at the time of discharge. Seven
      normal VLBW infants were evaluated at 40 weeks postconception, and five normal
      term infants were examined as a control. The neonates were placed supine with
      their heads in the neutral position. Data were obtained while the infant was
      resting quietly and breathing spontaneously prior to feeding. Pulmonary mechanics
      and energetics were measured with a CP-100 pulmonary monitor (Bicore Co. Ltd.).
      Pulmonary mechanics and energetics were determined by the least mean square
      technique. Dynamic compliance (Cdyn), resistance (Rtot, Re), and work of
      breathing (WOB) were calculated for the total breath, and tidal volume, minute
      ventilation, ratio of inspiratory time to respiratory period (Ti/Ttot), and
      respiratory rate were measured. There were no significant differences between
      normal VLBW infants and term infants in regard to ventilation, mechanics, or
      energetics. Although the respiratory system of normal VLBW infants is immature at
      birth, its development caught up to term infants by the time of discharge.

PMID- 9565217
TI  - Permanent Erb's palsy: a lack of a relationship with obstetrical risk factors.
AB  - Our objective was to investigate the association between permanent Erb's palsy
      and the presence of historic obstetrical risk factors. Cases of documented
      permanent Erb's palsy from our national registry of children with Erb's palsy
      were extracted and analyzed for the purpose of this descriptive study. Maternal
      and neonatal records were reviewed for demographic data, prenatal care, labor
      characteristics, delivery outcome, and long-term follow-up. Sixty-three infants
      with permanent Erb's palsy were identified. Seventeen (27.0%) mothers were
      nulliparous. Mean +/- SD (range) gestational age at delivery and birthweight were
      39.9 weeks +/- 1.3 (37-43) and 4501 g +/- 625 (3352-6905), respectively. Maternal
      and perinatal characteristics of these cases were (n [%]): nondiabetic-56 (89%);
      weight gain <40 lb-48 (76%); normal labor-57 (91%); 2nd stage <2.0 hr-54 (86%);
      midpelvic procedure-13 (21%); and shoulder dystocia-59 (94%). There were no
      statistically significant differences between patients with birthweight >4500 g
      (n = 26 [41%]) and those with birthweight < or =4500 g (n = 37 [59%]). These data
      suggest that historic risk factors for neonatal brachial plexus injury may not be
      associated with permanent Erb's palsy.

PMID- 9565218
TI  - Low weight/length ratio to assess risk of cerebral palsy and perinatal mortality
      in twins.
AB  - The etiology of increased rates of cerebral palsy (CP) in twins is unclear, but
      likely is associated with growth retardation, which occurs more often in twins.
      Asymmetric growth restriction, a form of growth retardation, has been found
      associated with increased rates of perinatal morbidity in infants with normal
      centile birthweights, and occurs more often in twins. Data from 55,457 infants
      were evaluated. Associations between twinning, CP, and neonatal mortality were
      evaluated. Influences of confounding factors, such as prematurity, perinatal
      depression, and asymmetric growth were assessed. Although twinning was a
      significant univariate correlate of both CP and neonatal mortality, low
      weight/length ratio (a marker of asymmetric growth) was a better correlate of
      both outcomes, and twinning was not significantly associated with either outcome
      after logistic adjustment for factors such as prematurity, perinatal depression,
      and low weight/length ratio. Low weight/length ratio occurred more often in twins
      of advancing gestational age, supporting a hypothesis of competition for
      nutritional resources as the cause for increased rates of low weight/length ratio
      in twins as compared with singletons. Asymmetric growth restriction is an
      important correlate of neonatal morbidity in twins, and should be considered when
      these factors are assessed in infants from multiple gestations.

PMID- 9565219
TI  - Ascertainment of 68,XX double aneuploidy by midtrimester biochemical screening: a
      case report.
AB  - A fetus with 68,XX karyotype was ascertained by an elevated midtrimester MSHCG.
      By antenatal ultrasound, the only unusual finding was in relation to the
      placenta. Preterm delivery was mandated by the development of severe
      preeclampsia. Postmortem examination of the stillborn fetus demonstrated no
      abnormal physical findings other than bilateral syndactyly of fingers and toes.

PMID- 9565220
TI  - Nonimmune hydrops fetalis due to congenital syphilis associated with negative
      intrapartum maternal serology screening.
AB  - We present an unusual case, in which a woman presenting with markedly decreased
      fetal movements at 29 weeks gestation following a recent increase in fundal
      height was noted sonographically to have fetal hydrops consisting of scalp edema,
      marked hepatomegaly, ascites, and polyhydramnios. No lethal structural congenital
      anomaly was noted. Admission laboratory examinations revealed a negative antibody
      screen and a negative RPR. Emergent cesarean section was performed due to
      prolonged fetal bradycardia during biophysical profile testing. The acidotic
      hydropic neonate weighing 1825 g was resuscitated yet succumbed at 3 hr of life
      following intravenous administration of antibiotics. Neonatal blood was RPR
      positive at 1:16. Postmortem pathology examination demonstrated severe multiorgan
      system failure secondary to overwhelming congenital syphilis. Extensive
      extramedullary hematopoiesis was noted and histopathology with Dieterle stains
      revealed numerous hepatic spirochetes. Postpartum reexamination of the maternal
      blood with serial dilutions revealed a positive RPR at 1:1024. This case
      emphasizes that initial negative screening for syphilis may be seen despite
      overwhelming infection, a condition that has been termed the "prozone effect."

PMID- 9565221
TI  - Effect of prenatal diagnosis of critical left heart obstruction on perinatal
      morbidity and mortality.
AB  - We sought to determine the effect of prenatal diagnosis of congenital heart
      disease, specifically critical left heart obstructive (LHO) lesions, on postnatal
      morbidity and mortality. Several studies have found no significant improvement in
      mortality in infants with prenatally detected heart disease compared to infants
      diagnosed postnatally. Few reports have focused on the specific effects of
      prenatal diagnosis on the perinatal course. All newborns with LHO seen between
      July 1993 and July 1996 were identified and divided into two groups based on
      prenatal vs. postnatal diagnosis. Hospital records were reviewed for demographic
      and outcome variables. The outcome variables included degree of metabolic
      acidosis, hemodynamic instability, noncardiac organ dysfunction, delayed surgical
      intervention, and surgical mortality. Twenty-three fetuses were diagnosed with
      LHO lesions. Postnatally, 45 newborns presented with LHO anomalies. Prenatal
      diagnosis resulted in avoidance of hemodynamic compromise, reduced organ
      dysfunction, and reduced surgical delays. There was no significant difference in
      surgical mortality. Prenatal diagnosis significantly decreases postnatal
      morbidity in infants with LHO lesions. Although surgical results are similar, the
      reduced morbidity decreases surgical delays and potentially may impact on
      neurodevelopmental outcomes.

PMID- 9565222
TI  - Plasma leptin concentrations in newborns of diabetic and nondiabetic mothers.
AB  - Leptin plays an important role in regulating body composition through modulation
      of appetite and energy expenditure. We hypothesized that leptin levels in
      umbilical cord blood correlate with newborn body weight and habitus. We also
      hypothesized that infants of diabetic mothers would demonstrate altered leptin
      metabolism. Venous blood was sampled at birth from the umbilical cords of 105
      infants (74 infants of nondiabetic mothers, and 31 infants of diabetic mothers).
      Thirty-nine mothers had plasma leptin concentrations measured. Analysis was done
      using Student's t-test, Pearson's correlation, and Spearman's correlation.
      Univariate/multivariate regression was used for analysis of factors associated
      with leptin concentration in umbilical cord plasma. Maternal and newborn
      characteristics were correlated with log leptin levels in umbilical venous
      plasma. Leptin concentration in umbilical cord plasma correlated best with birth
      weight for newborns of both nondiabetic and diabetic mothers (p < 0.01 for
      either). Umbilical cord plasma concentration of leptin was higher in infants of
      diabetic mothers than in infants of nondiabetic mothers (2.53 +/- 1.09 vs. 1.76
      +/- 0.82; p < 0.001). Multiple regression analysis revealed a significant (p <
      0.01) relationship between umbilical cord leptin level and newborn birth weight,
      as well as maternal DM, but not with gestational age. Similarly, there was no
      significant correlation with maternal plasma leptin concentration. The strong
      correlation of leptin concentration in umbilical cord plasma with newborn birth
      weight, and the lack of significant correlation with maternal leptin plasma
      levels, suggest that normal fetal leptin metabolism reflects fetal size and/or
      body habitus independent of maternal leptin metabolism. On the other hand, the
      higher umbilical plasma levels in infants of diabetic mothers may reflect an
      influence of altered fetal insulin homeostasis on fetal leptin metabolism, and
      suggests that maternal diabetes may influence fetal leptin metabolism.

PMID- 9565223
TI  - The effect of polyhydramnios and oligohydramnios on fetal lung maturity indexes.
AB  - The influence of amniotic fluid (AF) volume on common fetal lung maturity (FLM)
      indices was evaluated. Cases diagnosed with altered AF volume as estimated by
      ultrasound (n = 71; polyhydramnios = 33, oligohydramnios = 38) were matched to
      controls by: gestational age (GA) at amniocentesis, GA at delivery, neonatal
      weight, sex, and pregnancy complication. FLM was assessed on AF specimens
      obtained by transabdominal amniocentesis by planimetric and stechiometric L/S,
      phosphatidylglycerol (PG), and lamellar bodies counts (LB). In cases with
      polyhydramnios, L/S ratios (planimetric and stechiometric) were statistically
      lower in cases with respect to controls (2.1 +/- 0.9 vs. 2.8 +/- 1.0, p = 0.007,
      and 4.8 +/- 2.4 vs. 5.9 +/- 2.7, p < 0.04; respectively). Absence of PG was more
      frequent in (70.8% vs. 50%, p = 0.02). LB counts were lower in cases than in
      controls (15.5 +/- 12.1 x 10(3)/microL vs. 21.9 +/- 14.3 x 10(3)/microL, p <
      0.05). In cases with oligohydramnios, no difference was found for planimetric and
      stechiometric L/S in comparison to controls (2.6 +/- 1.2 vs. 2.6 +/- 1.0, N.S.
      and 4.9 +/- 2.1 vs. 4.6 +/- 1.8, N.S.; respectively), absence of PG (62.5% vs.
      50%, N.S.), and LB counts (27.2 x 10(3)/microL +/- 12.8 x 10(3)/microL vs. 28.6 x
      10(3)/microL +/- 24.1 x 10(3)/microL, N.S.). In conclusion, oligohydramnios was
      not associated with altered FLM indices; in cases with polyhydramnios all FLM
      indices were significantly lower.

PMID- 9565225
TI  - Diagnosis and management of pheochromocytoma in pregnancy: a case report.
AB  - Pheochromocytoma is a rare tumor which causes increased levels of circulating
      catecholamines. During pregnancy, this condition is life threatening to both
      mother and fetus. A case report of pheochromocytoma diagnosed in the third
      trimester is presented along with a review of the diagnosis and treatment of
      pheochromocytoma in pregnancy.

PMID- 9565224
TI  - Prenatal MRI evaluation of giant neck masses in preparation for the fetal exit
      procedure.
AB  - Airway compromise at birth can be anticipated with giant neck masses, so that as
      much anatomic information as possible is necessary prior to delivery to establish
      a diagnosis and assess the airway. With this study, we evaluated the usefulness
      of prenatal magnetic resonance imaging (MRI) for evaluation of giant fetal neck
      masses prior to operating on placental support, the Ex Utero Intrapartum
      Treatment (EXIT) procedure, performed to secure the neonatal airway. Three
      pregnant women with an ultrasound (US) diagnosis of fetal giant neck mass were
      referred for prenatal MRI. As this was our initial experience performing prenatal
      MRI, a variety of imaging sequences were used including spin-echo, fast gradient
      echo, half-fourier single shot turbo spin-echo (Haste), and echo-planar imaging
      (EPI). All sequences performed were able to demonstrate the fetal airway relative
      to the mass. In addition, the images were able to give a more global definition
      of the mass because of the larger field of view than could be obtained with MRI
      compared to US. The Haste sequence provided the best definition of a mass because
      of decreased motion artifacts. The prenatal diagnosis on MRI was teratoma in two
      and lymphangioma in one and was confirmed at birth. MRI provided essential
      information about the diagnosis and the anatomy of the giant neck masses and
      adjacent airway in three fetuses prior to selection for the EXIT surgical
      procedure.

PMID- 9565226
TI  - Gestational age can predict the need for prophylaxis with surfactant therapy.
AB  - Controversy exists as to whether prophylactic or rescue therapy with surfactant
      should be used in infants born at less than 30 weeks gestation. We developed the
      hypothesis that gestational age can be used to predict a need for prophylactic
      surfactant therapy. We designed this retrospective study to determine whether
      there was a gestational age below which one could accurately predict the need for
      prophylactic surfactant therapy in almost all infants and limit unnecessary
      treatment of infants. We conducted a retrospective study of infants born at 23-34
      weeks' gestation to determine the frequency with which surfactant therapy was
      used in a rescue strategy at each gestational age, and to ascertain the
      sensitivity, specificity, and predictive values of gestational age as a predictor
      of the use of surfactant therapy. There was a significant inverse correlation
      between gestational age and the proportion of infants treated with surfactant (r
      = -0.923, p < 0.001). A gestational age cut-off of 26 completed weeks' had a
      positive predictive value of 85% and a specificity of 96% for the need for
      surfactant therapy. We conclude that gestational age can be used to predict a
      need for surfactant therapy in premature infants. At our institution, the failure
      to attain 26 completed weeks' gestation will accurately predict the need for
      surfactant therapy and will result in unnecessary treatment of very few infants.
      We suggest that each institution caring for very low birth weight infants should
      examine its population to determine the gestational age at which they can
      accurately predict the need for prophylaxis with surfactant therapy.

PMID- 9565227
TI  - Urinary hydrocolpos, cloacal malformation and pre-axial polydactyly: a rare
      variant of neonatal hydrocolpos.
AB  - Hydrocolpos is characterized by a vaginal obstruction with cystic dilatation of
      the vagina. The latter is usually caused by accumulation of cervical and
      endometrial mucus but in rare instances urine is accumulated through a
      vesicovaginal fistula proximal to the obstruction. Hydrocolpos and
      hydrometrocolpos may be associated with other malformations, such as postaxial
      polydactyly, anal atresia, esophageal atresia, renal agenesis, genital anomalies,
      and cardiopathy. Each neonate presenting with hydrocolpos should be evaluated for
      other clinically silent malformations, such as hamartoblastoma of the
      hypothalamic region. We report a patient with urinary hydrocolpos and cloacal
      malformation; it is the first case of hydrocolpos with pre-axial polydactyly. We
      briefly describe embryogenesis of the different types of vaginal obstruction and
      discuss prenatal and neonatal diagnosis and differential diagnosis.

PMID- 9565228
TI  - The fetal admission test and intrapartum fetal death.
AB  - Our objective was to describe the admission and subsequent intrapartum fetal
      heart rate (FHR) patterns in 21 singleton term pregnancies with an intrapartum
      fetal death. Through a retrospective chart review, 21 pregnancies with a term
      intrapartum fetal death were divided into 2 groups based on the fetal admission
      test (FAT): Group I-reactive (one or more FHR accelerations of 15 bpm x 15 sec in
      the first 30 min of monitoring); and Group II-nonreactive (NR [the absence of
      accelerations]). The FAT was compared with the subsequent intrapartum FHR
      pattern. Of the 21 deaths, the FAT was reactive in 7 fetuses (33%) or NR in 14
      fetuses (67%). While the demographic features of these groups were statistically
      similar, Group II had higher rates of meconium (12 out of 14 (86%) vs. 2 out of 7
      [29%] p = 0.017) and admission FHR decelerations (9 out of 14 (64%) vs. 1 out of
      7 [14%] p = 0.06). In Group I, a sudden catastrophic event such as a uterine
      rupture produced a prolonged FHR deceleration in six fetuses (86%). One (14%)
      fetus died after a Hon pattern. In Group II, four patients had a stair steps to
      death pattern. Intrapartum fetal death can occur after a reactive or NR FAT. With
      a reactive FAT, a catastrophic event appears necessary to cause fetal death. The
      higher rates of meconium, FHR decelerations, and stair steps to death patterns in
      the NR group suggest the underlying basis for the fetal demise was related to
      preadmission fetal compromise.

PMID- 9565229
TI  - The effect of environmental temperature and body weight on growth rate and
      feed:gain of male broilers.
AB  - High environmental temperatures are detrimental to the growth and feed:gain of
      broilers. The objective of this research was to determine the effects of
      incremental differences in environmental temperature on growth and feed:gain. The
      data are needed for decisions about the profitability of energy inputs when
      managing the housing environment. In Trial 1, broiler chicks were reared as a
      group to 21 d on litter with constant lighting and with water and feed available
      for ad libitum consumption. They were then moved to 10 environmental chambers.
      Each chamber was set at a different temperature ranging from 21.1 C to 31.1 C in
      1.11 C increments. Weight gain and feed:gain were determined when the broilers
      were 28, 35, and 42 d old. In Trials 2 and 3, broilers were placed in the
      environmental chambers, and weight gain and feed:gain were determined for the 42
      to 49 d period. The data were analyzed statistically, and regression equations
      were obtained for growth and feed:gain. Equations were based on body weight and
      temperature, and the body weight equation was plotted as grams gain per bird per
      day. Feed:gain was plotted for that body weight and temperature. Body weight gain
      per day increased to a maximum with increasing weight and then declined. The body
      weight at the maximum rate of gain was inversely related to temperature.
      Feed:gain increased as body weight increased. Feed:gain was directly related to
      temperature at weights above 800 g and the effect of temperature increased as
      body weight increased. The data will be useful for the evaluation of various
      management scenarios to determine the inputs that are profitable.

PMID- 9565230
TI  - Self-selection of dietary protein and energy by broilers grown under a tropical
      climate: adaptation when exposed to choice feeding at different ages.
AB  - Three hundred broiler chicks (Hubbard) of both sexes were assigned to five
      feeding treatments: T0 received a complete diet (control), T1 was a choice
      feeding system with simultaneous access to an energy-rich feed (ground corn) and
      a protein concentrate (43.7% CP), and T2, T3, and T4 were introduced to choice
      feeding after 1, 3, and 5 wk, respectively, of consuming the complete diet. At 1
      d-old, T1 chicks showed a marked preference for corn, with only 21.4% of their
      intake being the protein concentrate diet. Intake of the concentrate
      progressively increased to 40 to 45% after 3 d of adaptation, resulting in diets
      with 22.5 to 24.3% CP. When broilers fed the complete diet for 1 to 5 wk (T2, T3,
      T4) were changed to choice feeding, on the 1st d, their feed choice intake was
      similar to that of T1 chicks at the same age. Visual observation and tactile
      assessment of the feed particles during the initial period allowed the chicks to
      quickly evaluate the new feeds and to adapt their feeding behavior. Although
      total feed intake to 6 wk of age was not significantly affected by the feeding
      treatments, broilers on choice feeding selected diets with a lower percentage of
      CP and had lower live body weights at 6 wk than those fed the complete diet (T0).

PMID- 9565231
TI  - Acute 2,4-dichlorophenoxyacetic acid intoxication in broiler chicks.
AB  - The acute toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D), a herbicide, was
      studied in chicks dosed with 100, 300, 500, or 600 mg 2,4-D/kg BW, by the oral
      route. Clinical, laboratory, and histopathological methods were used as
      indicators of toxicity. After acute exposure, the herbicide decreased motor
      activity and induced muscular weakness and motor incoordination; decreased weight
      gain; increased serum creatine kinase (CK) and alkaline phosphatase (AP)
      activities and serum uric acid (UA), creatinine (CR), and total proteins (TP)
      levels; and did not change serum aspartate aminotransferase (AST) or alanine
      aminotransferase (ALT) activities. These changes were time- and dose-dependent
      and reversible. The LD50 (lethal dose 50%) calculated for oral 2,4-D in chicks
      was 420 mg/kg BW (385 to 483). Chromatographic analysis of the serum of the
      intoxicated chicks showed the presence of the herbicide; the amount found was
      dose- and time-dependent, increasing from 2 to 8 h after exposure and decreasing
      afterwards. Histopathological post-mortem studies conducted on intoxicated chicks
      showed hepatic (vacuolar degeneration of the hepatocytes), renal (tubular
      nephrosis), and intestinal (hemorrhagic) lesions. Taken together, the observed
      alterations mainly reflected kidney and muscle tissue damage, although hepatic
      toxicity may also have occurred after acute 2,4-D intoxication.

PMID- 9565232
TI  - Antioxidant defenses in lung lining fluid of broilers: impact of poor ventilation
      conditions.
AB  - Lung lining fluid antioxidants represent a potentially important protective
      barrier of lung epithelial cells to damaging effects of air pollutants, yet no
      information is apparently available concerning lung lining fluid antioxidants in
      broilers. Therefore, goals of this study were to establish uric acid, ascorbic
      acid, reduced (GSH) and oxidized (GSSG) glutathione, and protein concentrations
      in lung lining fluid obtained from male broiler chickens maintained for 6 to 7 wk
      within environmentally controlled rooms (Control) or chronically exposed to high
      levels of dust and ammonia within a broiler rearing house (House). The entire
      respiratory tract was carefully removed following an overdose of anesthetic and
      lavage fluid was collected after flushing the lungs with heparin-saline (10 mL
      per lung). There was no difference in GSH, but GSSG, uric acid, and protein
      concentrations were higher in House birds than in Controls. An increase in the
      GSSG to total glutathione (GSx) ratio, an indicator of oxidative stress, was also
      observed in birds maintained in the House environment. Ascorbic acid was not
      detected in House-reared birds and detected in only 4 of 12 Controls. Regression
      analysis revealed positive correlations between lung lining fluid protein and
      uric acid (r = 0.71; P < 0.01), protein and GSSG (r = 0.73; P < 0.01), and uric
      acid and GSSG concentrations (r = 0.69, P < 0.01). Additionally, GSSG was
      positively correlated (r = 0.66; P < 0.01) with the right ventricular weight
      ratio, an index commonly used in identifying the development of pulmonary
      hypertension syndrome in broilers. These data, the first to document lung lining
      fluid antioxidants in avian species, indicate an oxidative stress can be detected
      in fluid of broilers exposed to high levels of dust and ammonia in a simulated
      poultry house environment.

PMID- 9565234
TI  - Effects of dietary vitamin E on the immune system in broilers: altered
      proportions of CD4 T cells in the thymus and spleen.
AB  - To gain insight into the immunomodulatory effects of vitamin E (VE), immune cell
      population analyses were conducted using thymus and spleen from male broilers fed
      diets with various levels of VE supplementation (0, 17, 46, and 87 mg dl-alpha
      tocopherol acetate/kg of feed). At 2 and 7 wk of age, the percentages of B cells,
      macrophages, and T cell subsets, delineated by the expression of CD4, CD8, and T
      cell receptor (TCR) isotype, in thymus and spleen were determined by flow
      cytometry. The percentages of thymic and splenic B cells and macrophages from 2-
      and 7-wk-old chickens, as well as the percentage of thymic T cells in 2-wk-old
      chickens, were unaffected by VE treatment. However, 7-wk-old broilers maintained
      on 87 mg VE/kg feed had a higher percentage of CD4+CD8- thymocytes, a higher
      CD4+CD8- to CD4-CD8+ thymocyte ratio, and a lower percentage of CD4+CD8+
      thymocytes than chickens receiving no dietary VE supplementation. The VE-induced
      increase in the percentage of CD4+CD8- thymocytes was due to an increase in the
      TCR2+CD4+CD8- thymocyte subset, whereas the decrease in the percentage of
      CD4+CD8+ thymocytes involved all TCR defined T cell subsets. In the spleen, the
      percentage of CD4+CD8- T cells was lower in 2-wk-old chickens and higher in 7-wk
      old chickens maintained on 87 mg/kg feed than in chickens receiving no dietary VE
      supplementation. The decrease in CD4+CD8- splenocytes at 2 wk of age was due to a
      decline in the percentage of TCR2+CD4+CD8- splenocytes, whereas the increase in
      CD4+CD8- splenocytes in 7-wk-old chicks was due to an increase in the percentages
      of all TCR defined CD4+CD8- T cell subsets. These data support an
      immunomodulatory effect of VE on CD4+CD8- T cells.

PMID- 9565233
TI  - Effects of roxarsone and monensin on digital flexoral tendons of broiler
      chickens.
AB  - Roxarsone and monensin are common poultry feed additives that are used alone or
      in combination with other drugs to improve growth and feed utilization in young
      birds. The effects of monensin and roxarsone on the physiology of flexoral
      tendons of broiler chickens were examined to understand their relationships to
      leg weakness that have been occasionally associated with these drugs. Day-old
      chickens were fed either roxarsone or monensin for a period of 6 wk with two
      regimens of each of the drugs (roxarsone, 45.4 or 90.8 g/ton feed; monensin, 100
      or 150 g/ton feed). None of the treatments had any adverse effect on the growth
      of the birds or caused any significant leg problem. Roxarsone at 45.4 g/ton
      caused a significant gain in body weight. The biomechanical strength of digital
      flexoral tendons was measured in several ways. There were no statistical
      differences in load at break, the modulus of elasticity, or stress or strain
      levels between different treatment groups and birds that received no medication.
      There were no differences in collagen, proteoglycan, and pyridinoline content of
      tendons. Sequential extraction of tendons with different solvents revealed a
      significant increase in the percentage of guanidine HCl extractible collagens in
      monensin-treated birds, and a decrease in the acid extractible collagen in both
      roxarsone- and monensin-treated groups. The relative content of collagen in acid
      extractible collagens were significantly small relative to total collagen
      content. Majority of collagen (84 to 90%) was extractible with pepsin. About 8 to
      11% of total collagen was resistant to pepsin that was extractible with
      collagenase; this did not differ between treatment groups. Roxarsone treatment
      had no effect on the guanidine soluble collagen pool. The effect of monensin on
      the increase in guanidine soluble pool of collagen may relate to its disruptive
      effects on cellular secretory processes, which may be of significance in
      modulating connective tissue function in conjunction with other factors. However,
      in the present study, neither roxarsone nor monensin alone produced any
      significant leg problems nor caused any significant differences in the physiology
      of flexoral tendons or altered their biomechanical properties.

PMID- 9565235
TI  - Rfp-Y region polymorphism and Marek's disease resistance in multitrait
      immunocompetence-selected chicken lines.
AB  - Although the influence of the chicken classical MHC in resistance to many
      diseases is well established, the role of the recently identified, genetically
      independent, MHC-like region known as Rfp-Y is unclear. The objectives of this
      study were to analyze the frequencies of DNA polymorphisms of the Rfp-Y region in
      White Leghorn lines, which were divergently selected in replicate for multitrait
      immunocompetence, and to determine the association of these polymorphisms with
      Marek's disease (MD) resistance. Chicks, either with or without herpes virus of
      turkey (HVT) vaccination, were challenged with 500 ffu of a very virulent Marek's
      disease virus (Md5) at 2 d of age. The MD-related data were collected for 10 wk.
      PvuII-digested genomic DNA was hybridized with an Rfp-Y region-specific probe,
      18.1. Three Rfp-Y polymorphisms were observed. The frequency of one Rfp-Y
      polymorphism was significantly different between divergently selected multitrait
      immunocompetence lines in one replicate only; therefore, the impact of multitrait
      immunocompetence selection on Rfp-Y polymorphisms is inconclusive. The PvuII
      defined Rfp-Y region polymorphisms had no association with either innate or
      vaccine-induced MD resistance to Md5 virus challenge.

PMID- 9565236
TI  - Effects of dietary levels of vitamin A on the egg yield and immune responses of
      laying hens.
AB  - This research, which was designed and carried out as two consecutive experiments,
      investigated the effects of four different levels (0, 4,000, 12,000, and 24,000
      IU/kg) of vitamin A supplementation on egg yield, plasma vitamin A levels, and
      immune responses of laying hens. Transmission of maternal immunity to their
      descendants was also studied. In the first experiment, egg yield, blood vitamin A
      levels, and various parameters of the immune system such as T lymphocyte levels
      in the peripheral blood, plasma cell counts in the spleen, and antibody titers
      against Newcastle Disease Virus (NDV) in the sera were investigated for a 1-yr
      period. A total of 864 Hisex-brown laying hens were used in this experiment. The
      chicks were reared as commercial flocks until the 18th wk of age. No significant
      differences occurred among the parameters of the different diet groups. In the
      second experiment, maternal immunity was assessed in the chickens, supplied by
      hatching the eggs from hens in the first experiment. Maternal immunity was
      assayed by using the parameters as in Experiment 1. For this purpose, both blood
      and tissue samples were taken on the 2nd, 7th, and 10th d posthatch. Vitamin A
      supplementation had no significant effects on maternally, derived antibody titers
      or histologic structure of the lymphoid organs.

PMID- 9565237
TI  - Digestible lysine requirement of female turkeys during the starter period.
AB  - Three experiments were conducted to determine the digestible lysine requirement
      of female turkey poults during the starter period. Birds were fed a standard corn
      soybean meal diet until the onset of each trial and were then randomly assigned
      to treatments that were fed for 2 wk. Dietary treatments included titrated levels
      of digestible lysine (1.18 to 1.72%) added to a basal corn-soybean meal diet with
      an intact crude protein content of either 21% (Experiment 1) or 18.4%
      (Experiments 2 and 3). All diets contained 3,100 to 3,200 kcal MEn/kg. True
      digestible lysine contents of the basal diets were 1.42% (Experiment 1) and 1.18%
      (Experiments 2 and 3), based on digestibility assays of corn and soybean meal
      with cecectomized turkeys. A positive control diet (28% CP, 3,175 kcal MEn/kg)
      was also included in the treatments for comparison. Other amino acids were
      maintained at levels in relation to lysine based on previous research and the
      Illinois Ideal Chick Protein. Broken-line analysis suggests that the digestible
      lysine requirement is 1.32% for optimum body weight gain and 1.34% for optimal
      feed:gain at the energy levels used in these studies.

PMID- 9565238
TI  - Fermentation of soybean meal with Aspergillus usamii reduces phosphorus excretion
      in chicks.
AB  - Fermentation with Aspergillus usamii almost completely degrades phytate
      phosphorus in soybean meal. Phosphorus excretion was investigated in chicks fed a
      fermented soybean meal-based diet. Thirty chicks were fed one of three
      experimental diets; a control soybean meal-based diet (total phosphorus, 5.2
      g/kg; nonphytate phosphorus, 2.3 g/kg), a control soybean meal-based diet with
      added inorganic phosphorus (total phosphorus, 7.1 g/kg; nonphytate phosphorus,
      4.0 g/kg), or a fermented soybean meal-based diet without supplemental inorganic
      phosphorus (total phosphorus, 5.8 g/kg; nonphytate phosphorus, 3.9 g/kg) for 4
      wk. Body weight gain, the amount of retained phosphorus, and femoral phosphorus
      content were lower in the control group than in the phosphorus-supplied group and
      the fermented soybean meal group. The latter two groups showed similar body
      weight gain and femoral phosphorus content. On the other hand, phosphorus
      excretion was markedly more in the phosphorus-supplied group than in the other
      groups. As a result, phosphorus retention (percentage of intake) was lower in the
      phosphorus-supplied group than in the fermented soybean meal group. In
      conclusion, fermentation improved phosphorus bioavailability in soybean meal and
      supplemental inorganic phosphorus was not necessary for the fermented soybean
      meal-based diet, which remarkably reduced phosphorus excretion.

PMID- 9565239
TI  - Phytase activity in the small intestinal brush border membrane of the chicken.
AB  - The kinetics, mineral dependency, and pH dependency of phytate hydrolysis by
      preparations of chicken small intestinal brush border membrane vesicles were
      determined. Substantial phytate hydrolysis occurred over the pH range from 5 to
      6.5 with a maximum hydrolysis at pH of 6. Inclusion of 25 mM MgCl2 in the media
      doubled the rate of phytate hydrolysis. The brush border was shown to have no
      nonspecific acid phosphatase activity and excess phytate had no effect on
      alkaline phosphatase activity at pH 11. Under optimal conditions of pH 6 plus 25
      mM MgCl2, a kinetic model of a single Michaelis-Menten type of enzymatic activity
      with a Km of 0.160 +/- 0.008 mM and a Vmax of 42.5 +/- 1.0 nmol/mg vesicle
      protein per min plus a small unsaturable component converged to the data (P <
      0.05). The specific and total activities of intestinal brush border phytase were
      highest in the duodenum (P < 0.05) and decreased progressively down the length of
      the gut. Intestinal brush border vesicles prepared from broiler chicks and mature
      laying hens had comparable specific phytase activity. However, the total activity
      of brush border phytase was 35% higher in the small intestine of laying hens (P <
      0.05). Intestinal brush border phytase could contribute to phytate-phosphorus
      digestibility and may be subject to regulation in response to the dietary
      phosphorus and vitamin D status of the chicken.

PMID- 9565240
TI  - The lysine requirement and ratio of total sulfur amino acids to lysine for chicks
      fed adequate or inadequate lysine.
AB  - Experiments (Exp.) were conducted with Cornish Rock males (4 to 14 or 15 d of
      age) to determine the Lys requirement (Exp. 1) and the optimum ratio of TSAA:Lys
      for chicks fed adequate or inadequate Lys (Exp. 2). In Exp. 1, 180 chicks were
      allotted on the basis of BW to six treatments with six replications of five
      chicks each in a completely randomized design (CRD). Average initial and final BW
      were 73.5 and 415.5 g. The Lys levels fed were: 0.8, 0.9, 1.0, 1.1, 1.2, and 1.3%
      digestible Lys. In Exp. 2, 240 chicks were allotted on the basis of BW to 12
      treatments with four replications of five chicks each in a CRD. Average initial
      and final BW were 68.5 and 336.3 g. Chicks were fed either 0.82 or 1.0%
      digestible Lys and within each Lys level, a ratio of TSAA:Lys of: 0.55, 0.63,
      0.72, 0.80, 0.88, and 0.96, resulting in a 2 x 6 factorial arrangement of
      treatments. At the end of each trial, all chicks were weighed and pen feed
      consumption was measured. In Exp. 1, average daily gain (ADG) and gain:feed (GF)
      increased (linear, P < 0.01; quadratic, P < 0.02) as dietary Lys increased. A
      cubic (P < 0.04) effect of Lys for average daily feed intake (ADFI) was observed.
      One-slope, broken-line regression models estimated Lys requirements of 1.0, 0.9,
      and 1.1% for ADG, ADFI, and GF, respectively. In Exp. 2, chicks fed 1.0% Lys had
      higher (P < 0.01) ADG, ADFI, and GF than chicks fed 0.82% Lys. Daily gain, ADFI,
      and GF increased (linear, P < 0.01; quadratic, P < 0.01) as TSAA:Lys increased.
      For ADG, ADFI, and GF, one-slope, broken-line regression models estimated
      required ratios of TSAA:Lys of 0.66, 0.71, and 0.63 for chicks fed 1.0% Lys and
      0.66, 0.67, and 0.63 for chicks fed 0.82% Lys. There were no differences (P >
      0.05) in the estimated ratios of TSAA:Lys required to maximize ADG, ADFI, and GF
      for chicks fed 0.82 and 1.0% Lys. Thus, similar ratios of an indispensable amino
      acid to Lys can be obtained when chicks are fed at or slightly below their Lys
      requirement.

PMID- 9565241
TI  - Effects of different levels of vitamins A and E on the utilization of
      cholecalciferol by broiler chickens.
AB  - Three experiments were conducted to determine the effects of high dietary levels
      of vitamins A and E on the utilization of cholecalciferol by broiler chicks. In
      Experiment 1, chicks were fed six levels of vitamin A (5,000, 10,000, 20,000,
      40,000, 80,000, and 160,000 IU/kg). Cholecalciferol (vitamin D3) was not added to
      the basal diet but all birds were exposed to ultraviolet (UV) fluorescent light.
      Body weight was decreased only at levels of vitamin A of 80,000 IU/kg or above.
      In Experiment 2, birds were exposed to UV fluorescent light or no UV light, two
      levels of dietary vitamin A (1,500 and 45,000 IU/kg) and three levels of dietary
      vitamin D3 (0, 500, and 2,500 IU/kg) in a 2 x 2 x 3 factorial arrangement. The
      high level of vitamin A reduced (P < 0.001) bone ash but only at a marginal level
      of vitamin D3 (500 IU/kg) and when the birds were not exposed to UV light. In
      Experiment 3, birds were exposed to UV fluorescent light or no UV light, two
      levels of dietary vitamin E (10 and 10,000 IU/kg) and three levels of dietary
      vitamin D3 (0; 500 and 2,500 IU/ kg) in a 2 x 2 x 3 factorial arrangement. The
      high level of vitamin E significantly (P < 0.05) reduced body weight, bone ash,
      plasma calcium, and increased rickets but only at 500 IU/kg of vitamin D3.
      Feeding 2,500 IU/kg of vitamin D3 overcame the effects of the high level of
      vitamin E, causing a significant (P < 0.05) interaction. Ultraviolet light also
      prevented the detrimental effects of the high level of vitamin E. The results of
      these studies indicate that high dietary levels of vitamins A and E negatively
      affected the utilization of vitamin D3 only when D3 was present at a marginal
      level (500 IU/kg) in the diet but not when it was synthesized in the bird by
      exposure to UV light or supplemented at 2,500 IU/kg in the diet.

PMID- 9565242
TI  - The reduction of heat production in exercising pigeons after L-carnitine
      supplementation.
AB  - Four groups (CS,CR,PS,PR) of nine trained male racing pigeons were deprived of
      feed for 1 d and then subjected to a respiration chamber test in order to study
      the effect of oral 1-carnitine supplementation on the energy metabolism during
      flight. One week before, groups CS and CR were orally supplemented with 90 mg of
      1-carnitine daily, whereas PS and PR were given a placebo. Groups CS and PS
      underwent flight simulation by electrostimulation of the breast muscles. Flight
      simulation increased heat production, kept respiratory quotient from decreasing,
      decreased thyroxine levels, and increased weight loss. L-Carnitine decreased the
      rise in heat production during electrostimulation but did not influence
      respiratory quotient, weight loss, or thyroid hormones. L-Carnitine
      supplementation in pigeons improves fatty acid combustion efficiency during heavy
      exercise.

PMID- 9565243
TI  - The influence of vitamin A on the utilization and amelioration of toxicity of
      cholecalciferol, 25-hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol in
      young broiler chickens.
AB  - Three experiments were conducted to determine the influence of vitamin A on the
      utilization and amelioration of toxicity of cholecalciferol (vitamin D3), 25
      hydroxycholecalciferol [25-(OH)D3], and 1,25-dihydroxycholecalciferol [1,25
      (OH)2D3] in young broiler chicks. Two levels of vitamin A (1,500 and 45,000 IU/kg
      or 450 and 13,500 microg) were fed in all experiments. In Experiment 1, chicks
      were fed six levels of vitamin D3 (0, 5, 10, 20, 40, and 80 microg/kg). High
      dietary vitamin A decreased bone ash (P < 0.001), and increased the incidence of
      rickets (P < or = 0.02). Linear and quadratic responses to vitamin D3 levels were
      significant (P < 0.01) for body weight, bone ash, incidence and severity of
      rickets, and plasma calcium. In Experiment 2, six levels of 25-(OH)D3 (0, 5, 10,
      20, 40, and 80 microg/kg) were added to the basal diet. Adding 25-(OH)D3
      increased (P < 0.001) body weight, bone ash, and plasma calcium, and decreased
      rickets and plasma vitamin A. Adding 25-(OH)D3 overcame the reduction in bone ash
      produced by high dietary vitamin A showing a significant (P < 0.02) interaction.
      In Experiment 3, six levels of 1,25-(OH)2D3 (0, 2, 4, 8, 16, and 32 microg/kg)
      were added to the basal diet. High dietary vitamin A increased (P < 0.01) the
      incidence and severity of rickets. Adding 1,25-(OH)2D3 increased (P < 0.01) body
      weight, bone ash, plasma calcium, and reduced rickets and plasma and liver
      vitamin A. Adding 1,25-(OH)2D3 overcame the reduction in bone ash, and the
      increase in rickets produced by high vitamin A was significant (P < or = 0.05).
      These results indicate that high dietary vitamin A (45,000 IU/kg) interferes with
      the utilization of vitamin D3, 25-(OH)D3 and 1,25-(OH)2D3, increasing the
      requirement for each of them. Moreover, 45,000 IU/kg of dietary vitamin A
      ameliorated the potential toxic effects of feeding high levels of vitamin D3, 25
      (OH)D3 and 1,25-(OH)2D3 to young broiler chickens. Further work is necessary to
      find the minimum levels of these vitamins needed to cause these effects.

PMID- 9565244
TI  - Taurocholate transport by brush border membrane vesicles from different regions
      of chicken intestine.
AB  - Taurocholate transport was studied in brush border membrane vesicles (BBMV)
      isolated from chicken small (duodenum, jejunum, and ileum) and large (proximal
      cecum and rectum) intestines, using a rapid filtration technique. The purity of
      the BBMV was verified by the finding that the specific activity of sucrase (a
      brush border membrane enzyme marker) was severalfold greater in vesicles than
      corresponding values in mucosal homogenate. The functional integrity of isolated
      BBMV was evaluated by the uptake of D-glucose, which showed a transient increase
      in the presence of Na+. A Na+-dependence of taurocholate uptake was shown in BBMV
      prepared from ileum, cecum, and rectum, as taurocholate transport was transiently
      increased (accumulation) in the presence of a Na+ gradient between the external
      medium and intravesicular medium. The magnitude of the accumulation was similar
      among ileum, cecum, and rectum. In contrast, BBMV prepared from duodenum and
      jejunum did not show any Na+-dependent taurocholate transport, as the
      taurocholate uptake was not affected when a Na+ gradient was replaced by a K+
      gradient. The use of taurochenodeoxycholate in the incubation medium inhibited
      Na+-dependent taurocholate transport in the ileum, cecum, and rectum. This study
      is the first to show the presence of a Na+-dependent bile salt transport in BBMV
      obtained from chicken ileum, proximal cecum, and rectum.

PMID- 9565245
TI  - Interactive effects of sodium bentonite and coccidiosis with monensin or
      salinomycin in chicks.
AB  - Three experiments (Exp.) were conducted to determine the interactive effects of
      sodium bentonite (NaB) with the efficacy of monensin (MON) or salinomycin (SAL)
      in coccidiosis-infected chicks. Male broiler chicks 5 to 14 d of age were used,
      and each treatment was replicated with eight (Exp. 1) or four (Exp. 2 and 3) pens
      of five chicks each. In Exp. 1, MON (80 ppm), NaB (0.50%), or MON+NaB were fed to
      uninfected and coccidiosis-infected (5 x 10(5) sporulated Eimeria acervulina
      oocysts on Day 2 of the Exp.) chicks in a 2 x 2 x 2 factorial arrangement of
      treatments. Experiment 2 was identical to Exp. 1, but SAL (30 ppm) replaced MON
      as the anticoccidial additive. In Exp. 3, MON (55 ppm) or SAL (22 ppm) were added
      individually or with NaB (0.50%) to diets for uninfected or coccidiosis-infected
      chicks. Coccidial infection reduced (P < 0.01) gain, feed intake, gain:feed,
      plasma carotenoids, and percentage tibia ash in all experiments. The MON and SAL
      additions increased these response criteria in infected chicks (coccidiosis by
      anticoccidial, P < 0.07), except MON did not increase (P > 0.10) feed intake or
      tibia ash in Exp. 3. In Exp. 3, NaB partially reduced the positive effect of MON
      on daily gain (NaB by MON, P < 0.03), and of SAL on feed intake (NaB by SAL, P <
      0.08). The NaB addition also increased gain:feed (P < 0.08), and the increase was
      greater in infected chicks (coccidiosis by NaB, P < 0.08). Also in Exp. 3, SAL
      increased feed intake more in chicks not fed NaB than in chicks fed NaB (SAL by
      NaB, P < 0.08). Dietary NaB (0.5%) may reduce the efficacy of MON and SAL in
      coccidiosis-infected chicks when these additives are added at less than
      recommended levels.

PMID- 9565246
TI  - Molecular characterization of endogenous viral genes of the avian leukosis virus
      family in an experimental population of brown-egg layers.
AB  - Retroviral DNA sequences similar to the exogenous avian leukosis virus can be
      found in the genome of many chicken breeds and have been identified as the ALVE
      family of endogenous viral (ev) genes. Most of them have been described by a
      restriction fragment length polymorphism (RFLP) procedure with two restriction
      enzymes and a full length viral probe. In order to facilitate the comparison of
      ALVE genes between strains, the nomenclature workshop held at the XXIV
      International Society for Animal Genetics Congress recommended that four enzymes
      and several viral subprobes be used to characterize each locus. This approach has
      been followed in the present study of a Rhode Island Red experimental population.
      A previous study had identified ev genes with the SacI and BamHI enzymes and the
      Rous-associated virus-2 probe (RAV-2). Chickens carrying only one ALVE locus at a
      time have been produced to facilitate the analysis. Additional enzymes (EcoRI,
      HindIII, and KpnI), the full probe RAV-2 and three viral subprobes for the gag,
      pol, and LTR regions have been used. In addition, a PCR diagnostic test has been
      used to search for homologies with the ALVE1 (= ev1), ALVE6 (= ev6) and evA loci.
      Currently, 12 loci have been identified precisely: three were identical to ALVE
      loci described previously, either in White Leghorns, ALVE6 and ALVE18 (= ev18) or
      in broilers (evB8). In addition, the evB8 locus was found to be identical to the
      evA locus previously described in brown-egg layers. Nine loci appeared specific
      to this Rhode Island Red population. Four of these specific loci were complete
      and one of them could be considered of characteristic of this population, because
      of its very high frequency. The remaining five specific loci showed small
      deletions, either in the pol region for one of them or in the env region for
      three of them or at the 3' long terminal repeat for one of them. Altogether, 5
      out of 12 loci were structurally complete, which could suggest that deleted
      proviruses may have been preferentially retained.

PMID- 9565247
TI  - Flow-dependent pulmonary vasodilation during acute unilateral pulmonary artery
      occlusion in Jungle Fowl.
AB  - Giant Jungle Fowl previously were shown to be highly resistant to the onset of
      pulmonary hypertension syndrome (PHS, ascites) under conditions that induce a
      substantial incidence of PHS in broiler chickens. In the present study, lightly
      anesthetized, clinically healthy 12- to 13-wk-old male Giant Jungle Fowl
      maintained a lower respiratory rate, a similar hematocrit, and superior arterial
      blood gas values when compared with 6-wk-old male broilers. Giant Jungle Fowl
      weighed less than broilers (1,860 +/- 19 vs 2,788 +/- 63 g, respectively) and had
      equivalent absolute values for pulmonary arterial pressure, cardiac output, and
      pulmonary vascular resistance. Acute unilateral pulmonary artery occlusion in
      Giant Jungle Fowl doubled the pulmonary vascular resistance and forced the right
      ventricle to propel a sustained 60% increase in blood flow through the
      vasculature of the unoccluded lung. A transient increase in pulmonary arterial
      pressure initially was required to overcome the vascular resistance of the
      unoccluded lung; however, flow-dependent vasodilation gradually reduced the
      pulmonary vascular resistance and permitted pulmonary arterial pressure to return
      toward control levels. Unilateral pulmonary artery occlusion also triggered an
      immediate reduction in the partial pressure of oxygen in arterial blood, and the
      gradual return of pulmonary arterial pressure toward control levels did not
      eliminate this ventilation-perfusion mismatch, which has been attributed to blood
      flowing too rapidly through the unoccluded lung to permit diffusive gas
      equilibration. The inherent capacity for flow-dependent pulmonary vasodilation
      may reduce the susceptibility of Giant Jungle Fowl to PHS by reducing the
      increment in pulmonary arterial pressure required to propel an elevated blood
      flow through the lungs.

PMID- 9565248
TI  - "Hotness" stability of chicken hot-wing products as affected by preparation
      methods and storage.
AB  - Chicken hot-drumettes containing 2% cayenne pepper were prepared using three
      different cooking methods and stored under two different temperatures for
      "hotness" evaluation. Results demonstrated that the hotness of the samples were
      highest when products were cooked in a microwave oven, followed by convection
      oven, and least hot by deep-fat frying. Regardless of the cooking method, the
      degree of hotness of the hot-drumette decreased drastically during refrigerated
      storage. Results also indicated that the loss of hotness was associated with the
      increase of 2-thiobarbituric acid (TBA) values in the product. The addition of
      antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene
      (BHT), rosemary, and sodium nitrate during preparation or vacuum packaging
      retarded lipid oxidation of chicken hot-drumettes and retarded the loss of
      hotness of the products during refrigerated storage.

PMID- 9565249
TI  - Thermal and rheological properties and textural attributes of reduced-fat turkey
      batters.
AB  - Currently, modified potato and tapioca starches are used as functional additives
      in formulating reduced- and low-fat frankfurters. However, cornstarches may serve
      as alternative sources for comminuted meat systems. Meat batters formulated with
      ground turkey, 2% sodium chloride, 25% distilled-deionized water (ice), and 4%
      starch, including acid-thinned dent corn (ATDC), cross-linked waxy maize (XLWM),
      cross-linked dent corn (XLDC), modified potato (MP), acid-thinned dent corn with
      xanthan gum (ATDCG), or modified tapioca (MT) were compared. Thermal and
      structural properties of the batters were evaluated using differential scanning
      calorimetry (DSC) and dynamic rheological testing. Cooking loss, reheating loss,
      and texture profile analysis (TPA) were determined for cooked turkey batters. The
      DSC peak temperatures ranged from 57.5 to 74.9 C, which correlated positively to
      onset temperatures of the storage moduli (G') for XLWM starch. Incorporation of
      XLWM, XLDC, MT, or MP starch into turkey batters resulted in significant
      reductions in cooking and reheating losses. The TPA results showed that 9.42,
      8.57, and 8.48 kg of force were required for 75% compression of cooked batter
      segments containing MP, XLDC, and XLWM starches, respectively. Segments prepared
      with ATDCG starch were the least firm and most springy of all starch-containing
      segments.

PMID- 9565250
TI  - Pentoxifylline decreases the incidence of multiple organ failure in patients
      after major cardio-thoracic surgery.
AB  - We assessed the safety and efficacy of intravenous pentoxifylline [3,7-dimethyl-1
      (5-oxohexyl)-xanthine] in patients at risk for developing multiple organ failure
      after major cardio-thoracic surgery in a single-center, randomized, placebo
      controlled study. Of 816 consecutive patients who underwent major cardio-thoracic
      surgery, 40 who had Acute Physiology and Chronic Health Evaluation II score
      values > or = 19 at the first postoperative day after the surgery were included.
      Patients were randomized to receive either placebo (control; n = 25) or
      intravenous pentoxifylline treatment (pentoxifylline; n = 15) at a dosage of 1.5
      mg/kg/h as an adjunct to standard supportive therapy. Main outcome measurements
      were duration of required ventilator support, intensive care unit stay, and
      incidence of renal failure. Thirty-seven patients were eligible for evaluation.
      No significant adverse events related to pentoxifylline treatment were observed.
      The duration of mechanical ventilation was significantly greater for control
      patients (8.3 +/- 3.1 days) compared with pentoxifylline-treated patients (3.1 +/
      .9 days; p < .05). Patients treated with pentoxifylline experienced fewer days
      on hemofiltration (1.2 +/- .8 vs. 6.8 +/- 3.3; p < .05) and a shorter intensive
      care unit stay (5.2 +/- 1.1 vs. 11.4 +/- 3.1 days). There were no intergroup
      differences in mortality. Mortality was 33% in the pentoxifylline group and 36%
      among control group patients. In conclusion, supplemental pentoxifylline
      treatment may decrease the incidence of multiple organ failure in patients at
      risk of systemic inflammatory response syndrome after cardiac surgery. Additional
      studies are required to determine the validity of the observed effects.

PMID- 9565251
TI  - Energy metabolism and fuel mobilization: from the perioperative period to
      recovery.
AB  - To determine the metabolic responses to surgical trauma, we assessed the rates of
      whole body (WB) proteolysis and glucose turnover using established isotopic
      techniques in combination with interorgan amino acid and substrate balances
      (using arteriovenous differences times flow) after laparotomy. Circulating levels
      of hormones and mediators known to affect these parameters were also examined.
      Mongrel dogs (n = 5-8 per group) were studied postoperatively under general
      anesthesia (immediate postoperative period) and at 3 days postoperatively (3 dPO)
      and 2 weeks later. Our results show that the immediate postoperative period is
      characterized by significant hyperglycemia, secondary to decreased glucose
      clearance (without any alterations in the rates of hepatic glucose production)
      and significant increase in gut proteolysis, with a mild increase in WB
      proteolysis. The gut proteolysis accounted for nearly 40% of WB proteolysis. At 3
      dPO, blood glucose levels returned to normal, whereas the rate of WB proteolysis
      was maximally increased. Gut proteolysis was mildly elevated and accounted for
      nearly 8% of WB proteolysis. All metabolic parameters were back to near basal at
      2 weeks postoperatively. These metabolic changes were accompanied by significant
      elevations in the plasma levels of endogenous morphine and cortisol and lower
      glucagon and insulin growth factor-I levels in the immediate postoperative period
      and at 3 dPO. These studies underscore the importance of the gut as a reservoir
      of amino acids during the immediate postoperative period, accounting for more
      than one-third of WB proteolysis. At 3 dPO, when maximal stimulation of WB
      proteolysis and amino acid oxidation are observed, the contribution from the gut
      is negligible and is most likely replaced by breakdown from skeletal muscle.

PMID- 9565252
TI  - Thermal injury induces macrophage hyperactivity through pertussis toxin-sensitive
      and -insensitive pathways.
AB  - C57BL/6 mice were subjected to a full thickness scald thermal injury covering 25%
      of their total body surface area, and thioglycollate elicited peritoneal
      macrophages (Mphi were isolated 4 days later. Mphi from injured mice produced
      significantly greater amounts of reactive nitrogen intermediates and tumor
      necrosis factor-alpha in response to lipopolysaccharide and lipid A. Pertussis
      toxin (PTX) treatment of Mphi dose-dependently inhibited reactive nitrogen
      intermediate production in Mphi from sham-treated mice; however, Mphi from
      injured mice were insensitive to PTX-mediated inhibition. Conversely, tumor
      necrosis factor-alpha production was enhanced by PTX treatment, with Mphi from
      injured mice being more sensitive than Mphi from sham-treated mice to this effect
      of PTX. These results indicate that thermal injury increases Mphi sensitivity to
      lipopolysaccharide by a mechanism that is both PTX sensitive and PTX insensitive,
      thereby suggesting a role for G proteins in the modulation of Mphi activity after
      thermal injury.

PMID- 9565253
TI  - Tissue-specific protein kinase C isoforms differentially mediate macrophage
      TNFalpha and IL-1beta production.
AB  - Macrophage subpopulations are differentially activated during sepsis, shock, or
      trauma; however, it is unknown whether inherent mechanistic and phenotypic
      differences exist between macrophage subpopulations that may account for region
      specific inflammation. We hypothesized that macrophage expression/function of
      protein kinase C (PKC) isoforms is tissue specific (alveolar versus peritoneal).
      Rat alveolar and peritoneal macrophages were each probed for the expression of
      PKC isoforms alpha, beta1, beta2, gamma, delta, epsilon, zeta, and theta by
      immunoblot. PKC isoforms alpha, beta1, beta2, and zeta were detected in both
      populations; however, isoforms epsilon, gamma, and eta were found in alveolar
      macrophages only. To investigate the functional role of the Ca2+-dependent PKC
      (cPKC) versus Ca2+-independent PKC (nPKC) isoforms, pan-PKC isoform inhibition
      (cPKC and nPKC), or cPKC isoform selective inhibition (alpha, beta1, beta2,
      gamma) was performed before endotoxin (lipopolysaccharide, Salmonella minnesota,
      100 ng/mL) stimulation in vitro. Pan-PKC isoform inhibition attenuated TNFalpha
      and IL-1beta production by each population; however, selective cPKC (alpha,
      beta1, beta2, gamma) inhibition decreased peritoneal, but not alveolar,
      macrophage TNFalpha production. IL-1beta production was not affected by cPKC
      inhibition in either population. CONCLUSIONS: 1) alveolar and peritoneal
      macrophages constitutively express different PKC isoforms; 2) alveolar
      macrophages uniquely express isoforms epsilon, gamma, eta; 3) TNFalpha production
      is regulated by cPKCs in peritoneal macrophages, but by nPKCs in alveolar
      macrophages; 4) nPKCs regulate IL-1beta production in both populations. These
      results suggest that tissue-specific PKC isoforms differentially mediate
      macrophage function, which may have important regulatory implications in the
      compartmentalization of immune function. Further understanding may allow region
      specific manipulation of inflammation.

PMID- 9565254
TI  - Alveolar macrophage response to remote organ injury.
AB  - Intestinal reperfusion (IR)-induced pulmonary edema has been related to
      endogenous pulmonary thromboxane A2 (TxA2) release. This study examines the
      hypothesis that alveolar macrophages (aMphis) activated during IR are an
      important cellular source of TxA2 in this model. Anesthetized Sprague Dawley rats
      underwent 120 min of intestinal ischemia and 60 min of reperfusion (IR) or sham
      operation (Sham). aMphis were isolated by bronchoalveolar lavage and incubated in
      Krebs buffer for 30 min, after which the supernatant was analyzed for TxB2
      (metabolite of TxA2) and prostaglandin E2. Other parameters of aMphi activation
      measured included lysosomal enzyme release (beta-glucuronidase), superoxide (O2-)
      release, and procoagulant activity. aMphis from animals sustaining IR generated
      more than twice as much TxA2 and prostaglandin E2 as did those isolated from
      controls (p < .05). Other evidence of aMphi activation included a nearly 100-fold
      increase in procoagulant activity, a 7-fold increase in beta-glucuronidase
      release, and a 2.5-fold increase in O2- release over that of controls (p < .05).
      These data suggest that TxA2 is a major eicosanoid product of aMphis during IR
      and that aMphis may be an important cellular participant in IR-induced pulmonary
      microvascular injury, either directly by releasing O2-, lysosomal enzymes, and
      pro-coagulant factors, or indirectly by generating TxA2.

PMID- 9565255
TI  - 8-ISO-PGF2alpha production by alveolar macrophages exposed to hyperoxia.
AB  - Oxygen exposure for a sufficient duration at high partial pressure results in
      pulmonary edema in humans and animals. Although the specific mediators of oxygen
      toxicity are unknown, evidence suggests that oxygen-based radicals such as
      superoxide anion (O2.) are increased in the lungs in the presence of hyperoxia
      and contribute to this injury. A series of isomeric prostanoid compounds, the
      isoprostanes, are formed by the free radical-initiated lipid peroxidation of
      arachidonic acid (AA). One of these isomers, 8-iso-PGF2alpha, is elevated in the
      bronchial alveolar lavage fluid of rats exposed to 90% oxygen for 48 h and is
      associated with a significant increase in protein accumulation in the pulmonary
      extravascular space. Alveolar macrophages (AMs) are capable of producing large
      quantities of (O2.), suggesting a role in pulmonary oxygen toxicity. We
      hypothesized that isolated rat AMs exposed to hyperoxia generate increased amount
      of 8-iso-PGF2alpha. AMs were exposed to air or 90% oxygen for 6, 12, 24, 48, 72,
      96, and 120 h in the absence and presence of AA and/or calcium ionophore (A23187)
      and 8-iso-PGF2alpha was measured in the culture media. Exposure of primary
      cultures of AMs to 90% oxygen resulted in a significant increase in 8-iso
      PGF2alpha in the media (25 +/- 2 pg/mL) compared with air-exposed controls (14 +/
      1 pg/mL). The addition of 10 microM AA and 2 microM A23187 to the culture media
      resulted in a marked increase in 8-iso-PGF2alpha production by AMs exposed to air
      and 90% oxygen. However, treatment of AMs with the combination of AA and A23187,
      followed by exposure to 90% oxygen for 72 h, resulted in a 27-fold increase in 8
      iso-PGF2alpha compared with media alone and 90% oxygen. AMs metabolized free and
      phospholipid-bound AA to 8-iso-PGF2alpha, an activity enhanced in the 90% oxygen
      environment. Finally, acetylsalicylic acid, a cyclooxygenase inhibitor and free
      radical scavenger, reduced but did not abolish production of 8-iso-PGF2alpha.
      This study provides evidence that AMs produce a free radical-mediated isomeric
      prostaglandin compound that may be involved in pulmonary oxygen toxicity.

PMID- 9565256
TI  - Low molecular weight heparin prevents the pulmonary hemodynamic and
      pathomorphologic effects of endotoxin in a porcine acute lung injury model.
AB  - Tumor necrosis factor alpha (TNF-alpha) activity, platelet and neutrophil
      degranulation and margination, and increased vascular permeability are central to
      the pathophysiology of endotoxin-mediated acute lung injury. Nonanticoagulant
      activities of low molecular weight heparin (LMWH) include solubilization of the
      TNF-alpha receptor protein, inhibition of neutrophil adhesion, and regulation of
      thromboxane B2 (TXB2) biosynthesis. In this study, we evaluated the ability of
      LMWH to modulate TNF-alpha and TXB2 activity during endotoxemia and the
      subsequent effects on pulmonary hemodynamics. Domestic pigs 8-10 weeks old were
      anesthetized and catheterized for standard cardiopulmonary measurements and the
      lungs harvested for cuff:vessel ratio, myeloperoxidase activity, and permeability
      index. Pigs were randomly assigned to one of four groups: lipopolysaccharide
      (LPS) (n = 6), given .5 microg/kg/h Escherichia coli LPS intravenously for 6 h;
      saline control (n = 5); LMWH (n = 5), given .5 mg/kg LMWH for 30 min, followed by
      .5 mg/kg/h; and LMWH + LPS (same dosages, n = 6). Administration of LPS resulted
      in increased plasma TNF-alpha and TXB2 activity; increased pulmonary arterial
      pressure, pulmonary vascular resistance, and alveolar-arterial oxygen tension;
      decreased systemic arterial oxygen tension; and pulmonary edema. The
      cardiopulmonary parameters for the LMWH-treated pigs did not differ from those of
      the saline-treated control pigs. Pretreatment with LMWH attenuated the LPS
      mediated TNF-alpha and TXB2 activity and attenuated LPS-mediated pulmonary
      hypertension, hypoxemia and neutrophil emigration, and edema formation. In
      conclusion, the data show that the protective effects of LMWH in this model of
      acute lung injury are associated with altered neutrophil adhesion and TNF-alpha
      and thromboxane activity.

PMID- 9565257
TI  - Gut endotoxin restriction improves postoperative hemodynamics in the bile duct
      ligated rat.
AB  - BACKGROUND: Postoperative hemodynamic disturbances in obstructive jaundice are
      associated with complications such as shock and renal failure. Gut-derived
      endotoxemia may underlie these complications. Recently, we have shown that
      cholestyramine treatment prevents gut-derived endotoxemia in bile duct-ligated
      (BDL) rats (Houdijk APJ, Boermeester MA, Wesdorp RIC, Hack CE, van Leeuwen PAM:
      Tumor necrosis factor unresponsiveness following surgery in bile duct-ligated
      rats. Am J Physiol 271: G980-G986, 1996). METHODS: The effect of cholestyramine
      on systemic hemodynamics and organ blood flows after a laparotomy was studied in
      2 wk BDL rats using radioactive microspheres. RESULTS: Compared with sham
      operated rats, postoperative BDL rats had 1) lower blood pressure (p < .05) and
      heart rate (p < .001) with higher cardiac output (p < .05), 2) lower splanchnic
      blood flow (p < .05), 3) lower renal blood flow (p < .01), and 4) higher
      splanchnic organ and renal-vascular resistances. Cholestyramine treatment in BDL
      rats prevented the postoperative decrease in blood pressure by increasing cardiac
      output (p < .01). In addition, cholestyramine maintained splanchnic blood flow at
      sham levels (p < .05). Furthermore, cholestyramine also prevented the fall in
      renal blood flow after surgery in BDL rats. CONCLUSION: Gut endotoxin restriction
      using cholestyramine treatment maintained normal blood pressure, improved
      splanchnic blood flow, and completely prevented the fall in renal blood flow in
      BDL rats. Reducing the gut load of endotoxin in patients with obstructive
      jaundice scheduled for abdominal surgery may prevent postoperative hemodynamic
      complications.

PMID- 9565258
TI  - Effect of aminoguanidine on plasma nitric oxide by-products and blood flow during
      chronic peritoneal sepsis.
AB  - We hypothesized that plasma nitric oxide (NO), generated via inducible NO
      synthase (iNOS) or endothelial constitutive NO synthase and measured via its by
      products NO2- and NO3- (NO2- + NO3- = NOx) would increase and remain elevated
      during chronic peritoneal sepsis. We further hypothesized that treatment with
      aminoguanidine (AG; 50 mg/kg), a selective iNOS inhibitor, would decrease NO
      production and alter blood flow. Sprague Dawley rats were randomized to septic
      and nonseptic groups. Septic rats received an intraperitoneal cecal slurry (200
      mg of cecal material/5 mL 5% dextrose-H2O/kg); control rats received sterile 5%
      dextrose-H2O (5 mL/kg) only. Plasma NOx and hemodynamics were measured 0, 4, 12,
      24, and 48 h after sepsis or sham induction. We also examined the effect of AG,
      an iNOS inhibitor, on plasma NOx levels and tissue blood flow at 24 h. Septic
      rats uniformly displayed signs of sepsis, including lethargy, piloerection, and
      diarrhea. NOx levels were significantly elevated compared with controls at 4, 12,
      24, and 48 h (p < or = .05). Septic rats also demonstrated hypotension (t = 12,
      24, and 48 h) and tachycardia (t = 4, 12, 24, and 48 h). The infusion of AG (50
      mg/kg intravenously for 30 min) at 24 h significantly decreased plasma NOx in
      septic animals. Plasma NOx concentrations returned to basal levels by 90 min
      after infusion of AG. In addition, blood flow studies demonstrated that AG
      treatment in nonseptic rats resulted in a significant decrease in blood flow to
      the stomach, skin, and adipose tissue, whereas AG infusion did not significantly
      alter the regional perfusion profile in septic animals. Furthermore, treatment
      with AG did not significantly alter mean arterial pressure in either group;
      however, nonseptic animals exhibited a decrease in stroke volume, and septic
      animals demonstrated an increase in heart rate. In contrast to the rise and fall
      of NOx levels in endotoxemia, this study demonstrates that the initial rise is
      sustained during 48 h of peritoneal sepsis. This sustained increase in NOx levels
      in this model correlated with the observable signs of systemic infection and may
      relate to enhanced iNOS activity. AG infusion demonstrated variable effects on
      regional tissue blood flow profiles in septic and nonseptic animals and
      attenuated the increase in plasma NOx levels in septic animals, an index of iNOS
      activity.

PMID- 9565259
TI  - Alterations in hepatic gluconeogenic amino acid uptake and gluconeogenesis in the
      endotoxin treated conscious dog.
AB  - We examined the effect of a 240 min intraportal infusion of a nonlethal dose of
      Escherichia coli endotoxin (.21 g x kg(-1) x min[-1]) on hepatic amino acid and
      glucose metabolism in chronically catheterized 42 h fasted conscious dogs (n =
      8). Hepatic metabolism was assessed using tracer (3-[3H]glucose [U-14C]alanine)
      and arteriovenous difference techniques. After endotoxin administration net
      hepatic glucose output increased twofold. Arterial plasma insulin levels
      decreased by 25%, whereas arterial plasma glucagon and cortisol levels increased
      10- and 6-fold, respectively. Arterial lactate levels increased 6.4-fold, whereas
      net hepatic lactate uptake was not increased. Arterial alanine levels (1.6-fold)
      and net hepatic alanine uptake (1.3-fold) increased, whereas net hepatic alanine
      fractional extraction was unaltered. In contrast, the arterial levels of the
      other gluconeogenic amino acids (glutamine, glycine, serine, and threonine)
      decreased. Despite this decrease, net uptake of these amino acids by the liver
      did not decrease, because net hepatic amino acid fractional extraction increased.
      Total net hepatic gluconeogenic precursor uptake was unaltered (1.1 +/- .1 to 1.3
      +/- .3 mg x kg(-1) x min(-1) expressed in glucose equivalents). In summary,
      gluconeogenesis does not increase after endotoxin administration. Thus, an
      increase in net hepatic glycogenolysis accounts for the majority of the increase
      in hepatic glucose production. The lack of an increase in alanine fractional
      extraction, despite hyperglucagonemia and a rise in the fractional extraction of
      other gluconeogenic amino acids, suggests that endotoxin specifically impairs
      hepatic alanine entry in vivo.

PMID- 9565261
TI  - Condylar remodelling and resorption after Le Fort I and bimaxillary osteotomies
      in patients with anterior open bite. A clinical and radiological study.
AB  - A sample of 259 patients with vertical maxillary hyperplasia, mandibular
      hypoplasia and anterior vertical open bite, collected from three different
      institutions, was analysed regarding temporomandibular joint (TMJ) sounds,
      condylar remodelling, and condylar resorption. All patients underwent Le Fort I
      osteotomies, and bilateral sagittal split advancement osteotomies were performed
      in 117 patients. Intraosseous wire fixation was used in 149 and rigid internal
      fixation in 110 patients. Cephalometric and orthopantomographic radiographs were
      available before surgery, immediately after surgery, one year postoperatively and
      at the latest follow up. The mean follow up was 69 months (range 20-210 months).
      The number of patients with TMJ sounds decreased from 38% to 31%. At the latest
      follow up 23.6% of the patients showed condylar remodelling, 7.7% unilateral
      condylar resorption and 7.7% bilateral condylar resorption. Condylar contours, as
      assessed on orthopantomographic radiographs, were classified as five different
      types. Condyles with preexisting radiological signs of osteoarthrosis or having a
      posterior inclination were at high risk for progressive resorption. Female
      patients with severe anterior open bite, high mandibular plane angle and a low
      posterior-to-anterior facial height ratio, who underwent a bimaxillary osteotomy,
      were prone to condylar resorption. Bone loss was predominantly found at the
      anterior site of the condyle. The incidence of condylar resorption was
      significantly higher after bimaxillary osteotomies (23%) than after only Le Fort
      I intrusion osteotomies (9%). Avoidance of intermaxillary fixation by using rigid
      internal fixation tended to reduce condylar changes, in particular in patients
      who underwent only a Le Fort I osteotomy. Rigid internal fixation in bimaxillary
      osteotomies resulted in condylar remodelling in 30% and progressive condylar
      resorption in 19% of the patients. Condylar changes were not significantly
      different after using either miniplate osteosynthesis or positional screws in
      bilateral sagittal split osteotomy procedures.

PMID- 9565260
TI  - Anti-intercellular adhesion molecule-1 antibody and intercellular adhesion
      molecule-1 gene deficiency do not prevent pulmonary neutrophil recruitment in
      polymicrobial sepsis.
AB  - The intercellular adhesion molecule (ICAM)-1 is expressed constitutively in
      normal lungs and increased in pulmonary inflammation. Whether increased ICAM-1
      expression in the lung contributes to neutrophil sequestration during lung
      inflammation in sepsis is unclear. We tested this hypothesis in mice after
      systemic sepsis from cecal ligation and puncture (CLP). ICAM-1 expression in
      mouse CLP lung tissue was found to increase with time. The time course of lung
      ICAM-1 up-regulation correlated with increases in lung myeloperoxidase (MPO)
      activity and neutrophil sequestration by light microscopy. The monoclonal IgG2b
      rat anti-mouse antibody, an anti-ICAM-1 antibody (YN1/1.7), administered
      intravenously at doses of 3, 10, or 30 mg/kg, however, did not decrease the lung
      MPO levels compared with nonimmune rat IgG. In support of these findings, lung
      MPO content in ICAM-1-deficient mice that underwent CLP was significantly higher
      than similarly treated ICAM-1-sufficient mice. Our results suggest that
      neutrophil sequestration in the mouse lung after CLP is not dependent on ICAM-1.

PMID- 9565262
TI  - Isolated unilateral temporalis muscle hypertrophy. A case report.
AB  - A case of isolated unilateral temporalis muscle hypertrophy is presented. A
      review of the literature revealed only one report of temporalis hypertrophy,
      probably caused by psychogenic muscle hyperactivity. The temporalis muscle
      hypertrophy in the patient described was idiopathic and its management was
      surgical.

PMID- 9565263
TI  - Randomized prospective clinical trial of two implant systems for overdenture
      treatment: a comparison of the 2-year and 5-year results using the clinical
      implant performance scale.
AB  - In a prospective randomized clinical trial, edentulous patients were treated with
      dental implants and overdentures. The results of treatment with two IMZ implants
      connected by a Dolderbar, and a transmandibular implant (TMI) were compared. By
      using the clinical implant performance scale, the clinical and radiographic data
      were evaluated and compared after a two-year and five-year follow up. After the
      five-year follow up, significantly less problems and complications were recorded
      in the IMZ group than in the TMI group (Wilcoxon, P=0.03). When compared to the
      two-year follow up, there was, however, a gradual increase of scores on the
      clinical implant performance scale in the IMZ group, while in the TMI group only
      a slight increase was recorded.

PMID- 9565264
TI  - Speech, deglutition and life quality after intraoral tumour resection. A
      prospective study.
AB  - The aim of the present prospective study was to evaluate the functional sequelae
      and postoperative development of quality of life after intraoral tumour surgery
      in 40 consecutive patients with a squamous cell carcinoma of the floor of the
      mouth. Immediate reconstruction of intraoral soft tissues after tumour resection
      was accomplished by local flaps (cheek and tongue) (n=27) and by revascularized
      transfer of small bowel grafts (n=5) and myocutaneous/fasciocutaneous flaps
      (n=8). Mobility of the tongue was assessed by ultrasound. Quality of speech was
      analysed using the Freiburg speech intelligibility test. Life quality was
      assessed by the functional living index-cancer preoperatively and six months
      postoperatively. A significant decrease in both mobility of the tongue and
      quality of speech was registered. The most substantial effect on quality of
      speech resulted from decreased movement of the base and the dorsum of the tongue.
      A significant increase in life quality at the end of the study period occurred
      only in the group of patients without substantial reduction of intelligibility of
      speech, while no significant improvement of postoperative life quality of
      patients with more severe deterioration of speech quality was found.

PMID- 9565265
TI  - Reconstruction of the floor of the mouth with a fascial radial forearm flap,
      prelaminated with autologous mucosa.
AB  - To circumvent the disadvantages of extraoral skin within the oral cavity and to
      cover mucosal defects by mucosa, we successfully prelaminated the radial forearm
      flap by insertion of buccal mucosa in ten patients. In a first-step operation,
      free grafts of buccal mucosa were fixed to the forearm fascia and covered with an
      alloplastic sheet, separating the mucosa grafts and the dissected fascia between
      and around the grafts from the overlaying subcutaneous tissue. The dimension of
      the alloplastic sheet in the subcutaneous pocket was chosen according to the size
      of the desired flap. Underneath the alloplastic sheet, the mucosal grafts merged
      and the mucosal surface increased by advancing of epithelial cells under in vivo
      culture conditions. After two months, mucosal prelamination of the distal radial
      forearm fascia had led to thin, pliable and resistant fasciomucosal flaps with a
      mucosal surface up to 7x4 cm, allowing physiological intraoral reconstruction.
      The preservation of skin and subcutaneous tissue of the forearm also enabled
      primary wound closure, reducing donor-site morbidity.

PMID- 9565266
TI  - Oral malignant melanoma: long-term follow up in three patients.
AB  - Three patients with oral malignant melanoma, who survived for at least ten years
      after initial examination, are presented. The depth of tumor invasion was 5 mm or
      less in all patients. The first patient received surgery and postoperative
      immunotherapy and she had no recurrence more than 18 years after treatment. The
      second patient underwent surgery but had local recurrence after 11 years. He
      underwent resection and postoperative chemotherapy and was still alive more than
      14 years after initial examination. The third patient received radiotherapy and
      had metastasis nine months after treatment. Resection and radiotherapy were
      performed and the patient was alive more than 14 years after first presentation.

PMID- 9565267
TI  - Polymorphous low-grade adenocarcinoma of the sublingual gland.
AB  - A case of polymorphous low-grade adenocarcinoma occurring in the sublingual gland
      is described, followed by a brief discussion on the differential diagnosis. This
      is the first case ever reported of this entity occurring in the sublingual gland.
      This paper brings into question the early belief that this tumor is restricted to
      intraoral minor salivary glands.

PMID- 9565268
TI  - Bone regeneration after radicular cyst removal with and without guided bone
      regeneration.
AB  - In order to determine the degree of bone regeneration after removal of radicular
      cysts using guided bone regeneration (GBR), a prospective, controlled and
      randomized clinical study was performed. Thirty patients with radicular cysts
      were divided into three groups. One group, the control group (n=10 patients), was
      treated by enucleation and primary closure. The other two groups were treated by
      enucleation and primary closure but GBR was used in addition, using a resorbable
      membrane (n=10) and a nonresorbable membrane (n=10). The membranes were fixed
      with nonresorbable Memfix System screws. The residual volume and the density of
      the newly formed tissue was measured by computer-assisted tomography and computer
      assisted digital image analysis before enucleation and three and six months
      postoperatively. No statistical significance was found in density and residual
      volume between the three treatment groups after six months. These results suggest
      that GBR using membranes does not contribute to increased bone regeneration.

PMID- 9565270
TI  - An unusual case of preauricular swelling: a giant parotid sialocele.
AB  - This case report documents one of the more unusual causes of a swelling in the
      preauricular region, a parotid sialocele. It illustrates the relationship of
      trauma to sialocele formation, while suggesting that most cases can be managed by
      a conservative regime. A suitable surgical solution is outlined for more
      persistent cases.

PMID- 9565269
TI  - Otodental syndrome. A case report.
AB  - A 12-year-old boy with characteristic findings of otodental syndrome is
      presented. Abnormalities of deciduous and permanent dentition included bulbous
      canines, globe-shaped posterior teeth and agenesis of maxillary premolars. High
      frequency sensorineural hearing loss was demonstrated, and results of genetic
      studies indicated an autosomal dominant trait. This patient presented previously
      unreported findings, including generalized macrodontia, delayed mineralization of
      the mandibular premolars, and supplementary permanent maxillary canines.

PMID- 9565271
TI  - Mycosis fungoides with involvement of the oral mucosa.
AB  - Mycosis fungoides (MF) is a T-cell lymphoma that predominantly affects the skin.
      Involvement of the oral tissues in MF is rare. A case of MF with involvement of
      the maxillary gingiva and cervical lymph nodes is presented. Electron-beam
      radiation with 40 Gy and systemic chemotherapy with vincristine and interferon
      gamma produced almost complete remission of the oral lesion while the persistent
      pain was relieved.

PMID- 9565272
TI  - A carrier for clinical use of recombinant human BMP-2: dehydrothermally cross
      linked composite of fibrillar and denatured atelocollagen sponge.
AB  - The clinical applicability of a dehydrothermally cross-linked composite of
      fibrillar and denatured atelocollagen sponge (DCFD-AS), as a carrier of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) was evaluated in the rat
      subcutaneous pouch. After four weeks, DCFD-AS with rhBMP-2 formed compact bone,
      without undergoing significant changes in shape and size, by means of
      intramembranous ossification. The ultimate size, shape and location of induced
      new bone was accurately controlled by the carrier. Low antigenicity of soluble
      atelocollagen, cross-linking without chemicals, the combination of gelatin with
      fibrillar collagen, and the spongy structure probably all contributed to new bone
      formation through intramembranous ossification without inducing an inflammatory
      response. Atelocollagen sponge is easily sterilized, can be stored at room
      temperature, and can act as a rhBMP-2 carrier without the need for complex
      procedures.

PMID- 9565274
TI  - A comparative study of epithelialization of subcutaneous fascial flaps and muscle
      only flaps in the oral cavity. A rabbit model.
AB  - Epithelialization of subcutaneous fascial flaps and muscle-only flaps used for
      reconstruction of the oral mucosa were studied in a rabbit model. Angiography was
      performed to help to design a subcutaneous cervical fascial flap and a
      cleidomastoid muscle-only flap. These flaps were transferred into a
      mucoperiosteal defect on the mandibular alveolus. The flaps were gradually
      infiltrated by acute inflammatory cells from the periphery and then replaced by
      granulation tissue originating from the oral mucosa. The epithelialization was by
      secondary intention. An epithelial tongue from the surrounding epithelium
      migrated onto the granulating flaps with eventual coverage after three weeks.
      After two months, the muscle-only flap was covered by a poorly organized
      epithelium, different from the highly uniform epithelium in the fascial flap. The
      granulation tissue which replaced the muscle-only flap matured to fibrous tissue,
      associated with severe contraction. This was characterized by dense regular
      collagen fibers, no elastic fibers, and few capillaries, while the fibrous tissue
      which replaced the fascial flap was characterized by random collagen and elastic
      fiber morphology and numerous dilated blood vessels, and was associated with mild
      contraction. This experiment supports the view that the different extracellular
      matrices of these flaps may play a role in epithelial configuration and
      contraction.

PMID- 9565273
TI  - Guided jaw-bone regeneration using an experimental rabbit model.
AB  - The aims of this study were to evaluate the space-maintaining capacity of two
      biocompatible barrier materials and to assess the effect of barrier occlusiveness
      on the amount of regenerated bone. Defects were prepared in the edentulous area
      on both sides of the maxillas in 22 rabbits. The rabbits were divided into three
      groups. Gore-Tex augmentation material (GTAM) (ePTFE)-barriers were placed to
      cover the experimental defects and compared with totally occlusive or perforated
      titanium foils and uncovered control defects respectively. After four weeks of
      healing, histological analyses and morphometrical measurements demonstrated that
      the amount of regenerated bone tissue was about the same underneath the collapsed
      GTAM-barriers as in the controls. The highest degree of regeneration was obtained
      in defects underneath the titanium foils, particularly if they were perforated,
      whether or not they were covered by GTAM-barriers. It was concluded that the
      space-maintaining properties of a barrier may be at least as important as barrier
      occlusiveness when regenerating bone defects.

PMID- 9565275
TI  - Postoperative analgesia for iliac crest donor site. A personal view.

PMID- 9565276
TI  - Interrelationship between periodontics and adult orthodontics.
AB  - The purpose of this review article is to provide the dental practitioner with an
      understanding of the interrelationship between periodontics and orthodontics in
      adults. Specific areas reviewed are how periodontal tissue reacts to orthodontic
      forces, influence of tooth movement on the periodontium, effect of
      circumferential supracrestal fiberotomy in preventing orthodontic relapse, effect
      of orthodontic bands on the periodontium, specific microbiology associated with
      orthodontic bands, mucogingival considerations and time relationship between
      orthodontic and periodontal therapy. In addition, the relationship between
      orthodontics and implant restorations (e.g., using dental implants as orthodontic
      anchorage) will be discussed.

PMID- 9565277
TI  - Which periodontal changes are associated with HIV infection?
AB  - To assess the validity of diagnostic criteria for HIV-associated periodontal
      diseases, existing sets of criteria were applied post-hoc to cross-sectional data
      of the periodontal health of men with and without HIV and their ability to
      predict HIV infection was compared. Criteria for gingival or periodontal
      ulceration predicted HIV infection to a similar level. Criteria sensitive to
      erythema of the attached gingiva and interdental craters had high positive
      predictive values. Distinct gingival red bands did not predict HIV. 3 HIV
      associated periodontal changes were recognised: erythema of the attached gingiva;
      necrotising periodontal disease and interdental craters. Epidemiological research
      should also consider conventional gingivitis and lost periodontal attachment. The
      presence or absence of all 5 conditions should be recorded at each site.
      Hierarchies of diagnoses with only the most severe condition assigned to each
      individual swamp valuable information.

PMID- 9565278
TI  - The role of a dentine-bonding agent in reducing cervical dentine sensitivity.
AB  - This double-blind split-mouth trial with 16 adult patients investigated the
      ability of a dentine bonding agent (DBA) to reduce cervical dentine sensitivity.
      Following stimulation of pairs of teeth by conventional tactile and air blast
      stimuli, together with controlled evaporative and cold fluid stimuli, sensitivity
      was recorded using tactile threshold, visual-analogue scale (VAS) and short-form
      McGill pain questionnaire (SFMPQ), prior to and 1 week following treatment with
      DBA. Prior to assessment, subjects recorded their perceived overall sensitivity
      using VAS and SFMPQ. Application of each stimulus was separated by 10 min.
      Sensitivity was recorded by a clinician blinded to the treatment status of each
      tooth. The control tooth was treated by applying DBA to coronal enamel. Dietary
      information was collected after the post-treatment assessment. There was a
      significant (p<0.05) improvement in tactile threshold and air flow and air blast
      VAS scores, together with reductions in sensitivity to evaporative stimuli when
      assessed by SFMPQ. Treatment response was not influenced by the subjects' age,
      gender, diet, use of fluoride-containing or silica-based toothpastes or fluoride
      mouthwashes, or a history of previous sensitivity treatment. It is concluded that
      topical application of DBA is an effective way to reduce cervical dentine
      sensitivity.

PMID- 9565279
TI  - Flossing behaviour in English adolescents.
AB  - The aim of this study was to investigate the relation between flossing behaviour
      and other health, cleanliness and social behaviours in adolescents. Data from a
      survey of 41142, 12-16-year-old children from 244 secondary schools throughout
      England were analysed to obtain information about flossing frequency, dental
      attendance and recalled advice about flossing, and some general cleanliness and
      social behaviours. Subjects completed a questionnaire, anonymously, in class
      during normal school hours. Flossing frequency was found to change with age, its
      use becoming less frequent from age 12 through age 16 years. There was a
      significant relationship between flossing frequency and the time since the last
      dental attendance, the more recent attenders flossing more frequently. 6% of
      subjects recalled receiving advice about flossing at their last dental attendance
      and higher proportions of those who used floss recalled such advice, compared
      with non-flossers. Flossing frequency was also found to correlate positively with
      frequencies of washing hands after visiting the lavatory and bathing, and having
      a current friend of the opposite gender. There was only a small association
      between smoking habit and flossing, and only in school years 8 and 10: subjects
      most committed to smoking used floss slightly more frequently than those who did
      not smoke. Factor analysis showed evidence of gender differences in perceptions
      of flossing. Males equated use of floss with health-related behaviours while
      females associated flossing more with cleanliness behaviours. This finding is
      consistent with gender differences in toothbrushing behaviour reported in
      previous studies. The present study provides further insights into the history of
      dental flossing.

PMID- 9565280
TI  - Relationship between smoking and dental status in 35-, 50-, 65-, and 75-year-old
      individuals.
AB  - The aim of the present study was to examine the dental status and smoking habits
      in randomized samples of 35-, 50-, 65-, and 75-year-old subjects (n = 1093),
      recruited for a cross-sectional epidemiological study in the County of Varmland,
      Sweden. The following clinical variables were recorded by 4 well-calibrated
      dentists: number of edentuolous subjects, number of missing teeth, probing
      attachment level, furcation involvement, CPITN scores, DMF surfaces, plaque and
      stimulated salivary secretion rate (SSSR). In addition, the subjects reported in
      a questionnaire their tobacco habits, oral hygiene habits, dietary habits etc.
      The percentage of smokers in 35-, 50-, 65-, and 75-year-olds was 35%, 35%, 24%
      and 12%, respectively. In 75-year-olds, 41% of the smokers were edentulous
      compared to 35% of non-smokers. The difference in number of missing teeth between
      smokers and non-smokers was 0.6 (p=0.15), 1.5 (p=0.013), 3.5 (p=0.0007) and 5.8
      (p=0.005) in the 4 age groups. Smokers had the largest mean probing attachment
      loss in all age groups. The differences between smokers and non-smokers in mean
      attachment level were 0.37 (p=0.001), 0.88 (p=0.001), 0.85 (p=0.001) and 1.33 mm
      (p=0.002) in the 35-, 50-, 65-, and 75-year-olds, respectively. Treatment need
      assessed by CPITN was in all age groups greatest among smokers. The number of
      intact tooth surfaces was fewer in 35-, 50-, and 75-year-old smokers than in non
      smokers. The number of missing surfaces (MS) was higher in 50-, 65-, and 75-year
      old smokers than in non-smokers. In addition, 35-year-old smokers exhibited a
      significantly larger number of decayed and filled tooth surfaces (DFS) than non
      smokers. Male smokers had significantly higher SSSR than non-smoking males
      (p=0.012). Plaque index and oral hygiene were similar in smokers and non-smokers.
      Smokers reported a more frequent intake of sugar containing soft drinks (p=0.000)
      and snacks (p=0.003) than non-smokers. The opposite was reported for consumption
      of fruit (p=0.003). It was concluded that smoking is a significant risk indicator
      for tooth loss, probing attachment loss and dental caries.

PMID- 9565281
TI  - Protease activity in gingival crevicular fluid: presence of free protease.
AB  - Our aim was to study protease activity in GCF from inflamed sites with or without
      tissue destruction. 19 patients with both periodontitis and gingivitis sites and
      12 patients having gingivitis alone participated in the study. GCF samples were
      collected by an intracrevicular washing method. The protease activity was
      measured as degradation of FITC-conjugated casein. To obtain a semiquantitative
      estimate of the harvested GCF volume, we measured the transferrin concentration
      in the wash-fluid. The protease activity was significantly higher in the deep
      pockets in periodontitis patients than in shallow pockets in the same patients.
      This difference was still higher when the ratio of protease activity to the
      amount of transferrin in the sample was plotted. Although protease activity was
      lower in samples from gingivitis patients than in the deep pockets in
      periodontitis patients, the difference was not significant. About 90% of the
      activity could be inhibited by the addition of an excess amount of alpha-1
      antitrypsin (A1AT). This study shows that protease activity is higher in inflamed
      sites with tissue destruction than in inflamed sites without. Most of this
      activity could be inhibited by A1AT, which suggests that the activity is due to
      an imbalance between protease and antiprotease rather than to proteases
      insensitive to A1AT.

PMID- 9565282
TI  - Short chain carboxylic acids decrease human gingival keratinocyte proliferation
      and increase apoptosis and necrosis.
AB  - Epithelia are key barriers to infections. In periodontal disease, the gingival
      sulcular epithelium becomes ulcerated. In this report, we test the hypothesis
      that short-chain carboxylic acids (SCCA) inhibit keratinocyte proliferation,
      increase necrosis and apoptosis, and may thus promote ulceration. SCCA produced
      by bacteria are present at millimolar concentrations in the periodontal pockets
      of subjects with periodontal disease. SCCA concentrations are higher in subjects
      with severe disease than in those with mild disease, and are not detectable in
      healthy subjects. Cell proliferation is critical for maintenance of epithelial
      barrier function. All SCCA tested, when neutralized, decreased epithelial cell
      proliferation (as measured by 3H-thymidine incorporation) in a dose-dependent
      manner. We found that epithelial cell viability decreased with increasing SCCA
      concentrations, accounting at least partly for the decreased 3H-thymidine
      incorporation. For all conditions we tested, SCCA-induced apoptosis preceded and
      exceeded necrosis. While the molecular mechanism(s) for these effects remain to
      be determined, the results indicate that SCCA derived from caries- or periodontal
      disease-associated bacteria could alter gingival barrier function.

PMID- 9565283
TI  - The effectiveness of a magnetized water oral irrigator (Hydro Floss) on plaque,
      calculus and gingival health.
AB  - The purpose of this study was to evaluate the effects of a magnetized water oral
      irrigator on plaque, calculus and gingival health. 29 patients completed this
      double-blind crossover study. Each patient was brought to baseline via an oral
      prophylaxis with a plaque index < or = 1 and a gingival index < or = 1. Subjects
      used the irrigator for a period of 3 months with the magnet and 3 months without
      the magnet. After each 3 month interval, data were collected using the plaque
      index, gingival index, and accretions index. The repeated measures analysis on
      plaque, gingival and calculus indices yielded a statistically-significant period
      effect for PlI (p=0.0343), GI (p=0.0091), and approached significance for
      calculus (p=0.0593). This meant that the effect of irrigation resulted in a
      decrease of all indices over time. Therefore, the treatment effect on each index
      was evaluated using only the measurements obtained at the end of the first period
      (i.e., assuming a parallel design). Irrigation with magnetized water resulted in
      64% less calculus compared to the control group. The reduction was statistically
      significant (p< or =0.02). The reduction by 27% in gingival index was not
      statistically significant. The reduction in plaque was minimal (2.2%). A strong
      positive correlation between the plaque index and the Watt accretion index was
      observed. The magnetized water oral irrigator could be a useful adjunct in the
      prevention of calculus accumulation in periodontal patients, but appears to have
      minimal effect on plaque reduction. The results indicated a clinical improvement
      in the gingival index, but this was not a statistically significant finding.

PMID- 9565284
TI  - Periodontal effects of a biobehavioral prevention program.
AB  - The present study tested preventive regimens in older subjects using dental
      services sporadically. 297 persons aged 60-90 (mean age 72.8; 43% ethnic
      minorities), were randomly assigned to either a control group or four
      interventions with incrementally more complex preventive strategies; behavioral
      training (group 2), added weekly chlorhexidine rinse (group 3), added semi-annual
      fluoride varnish (group 4), and added semi-annual prophylaxis (group 5). The
      control group received dental care as they preferred, primarily emergency care.
      All subjects were re-examined annually for 3 years. At baseline, 190 (64%) of the
      subjects were considered at risk for future periodontal disease progression. At
      baseline there were no group differences for any clinical parameter studied.
      Gingival bleeding varied between 19% and 23% over time and with no group
      differences. After 1 year, the greater decrease in probing depth for group 5
      approached significance compared to the control group (p<0.06). Clinical
      attachment levels (CAL) improved in group 5 compared to the control group (p<0.01
      for mesio-buccal, p<0.05 for mid-buccal tooth surfaces). The group differences
      did not persist at year 3. At year 3 in group 1, 9.2% and in group 5, 4.9%
      subjects lost > or =2.0 mm CAL. 310 teeth (6.5%) were extracted during the study
      period. A 21% increased risk for tooth loss was found in group 2, a 15% reduced
      risk in group 3, a 28% reduced risk in group 4, and a 44% reduced risk in group 5
      compared to the control group (Wald-statistics robust p-value 0.12). At year 3,
      the tooth mortality rate in groups 3, 4 and 5 combined was reduced to 59% and
      significantly lower than groups 1 and 2 together (p<0.04). Self-efficacy was the
      best predictor of periodontal disease progression (F=7.02, p<0.01). Thus older
      persons benefited from a preventive oral health care program.

PMID- 9565285
TI  - Porphyromonas gingivalis, Prevotella intermedia and Bacteroides forsythus in
      plaque subjacent to bridge pontics.
AB  - This study examined the distribution of P. gingivalis, P. intermedia and B.
      forsythus in plaque on metallic and porcelain pontics adjacent to healthy and
      inflamed mucosa. Subpontic plaque was collected from 33 inflamed and 31 healthy
      sites. Plaque suspension was incubated with specific rabbit antisera to P.
      gingivalis (FDC 381), P. intermedia (ATCC 25261) and B. forsythus (FDC 335), and
      the labelled cells disclosed with fluorescein-labelled goat-anti-rabbit IgG by
      indirect immunofluorescence microscopy. Mean proportions of P. gingivalis, P.
      intermedia, and B. forsythus at inflamed sites were 0.60+/-0.75, 2.48+/-2.28, and
      0.44+/-0.64% respectively, and at healthy sites 0.21+/-0.43, 1.27+/-1.05, and
      0.15+/-0.18% respectively. These differences were statistically significant.
      Almost all sites were positive for P. intermedia, whereas only 12/31 healthy and
      21/33 inflamed sites were positive for P. gingivalis. 18/31 healthy and 28/33
      inflamed sites were positive for B. forsythus. P. intermedia was recovered in
      higher proportions from metallic pontics adjacent to inflamed sites (MI) than
      healthy sites (MH) or porcelain pontics next to inflamed (PI) or healthy sites
      (PH). P. gingivalis is was recovered in higher proportions from MI than PH. We
      conclude that both the nature of the pontic material and the health status of the
      mucosa affect the composition of the associated microbiota.

PMID- 9565286
TI  - Microbial factors and gingival crevicular fluid aspartate aminotransferase
      levels. A cross-sectional study.
AB  - The aim of this cross-sectional study was to investigate the clinical application
      of chairside tests for gingival crevicular fluid (GCF) aspartate aminotransferase
      (AST) levels and plaque BANA hydrolysis activity with the presence of the
      periodontal pathogens Porphyromonas gingivalis and Actinobacillus
      actinomycetemcomitans. The study comprised 100 periodontitis sites (pocket depths
      > or =4 mm, GI=3) from 10 patients with chronic adult periodontitis and 100
      control sites (pocket depths <4 mm, GI<3) from 10 periodontally healthy patients
      comprising 55 healthy sites (pocket depths <4 mm, GI=0) and 45 gingivitis sites
      (pocket depths <4 mm, GI=1 or 2). The values for both BANA hydrolysis and AST
      levels were significantly higher in samples from periodontitis compared with
      gingivitis and healthy sites (p<0.001). A. actinomycetemcomitans was identified
      in 45% and P. gingivalis in 17% of periodontitis sites but neither pathogen was
      recovered from control sites and there was no significant correlation with the
      clinical parameters measured. There was no significant relationship between the
      presence of P. gingivalis and/or A. actinomycetemcomitans with BANA hydrolysis or
      AST levels. A significant correlation (p=0.0017) was observed between BANA
      hydrolysis and pocket depth and between AST hydrolysis and the GI (p=0.01). This
      study failed to demonstrate a positive association between chairside analysis of
      GCF metabolites for AST levels and/or BANA hydrolysis with P. gingivalis and A.
      actinomycetemcomitans. However, the GCF metabolites had a significant correlation
      with periodontally diseased sites in patients with chronic adult periodontitis
      and may help confirm clinical observations.

PMID- 9565287
TI  - Langerhans cell histiocytosis presenting as bilateral eosinophilic granulomata in
      the molar region of the mandible. A case report.
AB  - Eosinophilic granuloma represents one of a triad of lesions encompassing a
      disease under the generic name, histiocytosis X or Langerhans cell histiocytosis.
      Localised eosinophilic granuloma, multifocal eosinophilic granuloma, Hand
      Schuller-Christian disease, and the most malignant form of histiocytosis,
      Letterer-Siwe disease, can all present as destructive bony lesions of the jaws.
      The present case was a 30-year-old man who presented with almost total
      destruction of the periodontal support to the left and right mandibular, 1st and
      2nd molars. Whereas the radiographic features were typical of eosinophilic
      granuloma, the clinical appearance and mirror image presentation were unusual.

PMID- 9565288
TI  - Mechanism of allergic contact dermatitis from propacetamol: sensitization to
      activated N,N-diethylglycine.
AB  - In order to confirm the mechanism of skin sensitization to propacetamol, a pro
      drug of acetaminophen, 3 patients with allergic contact dermatitis from
      propacetamol were patch tested with N,N-diethylglycine phenyl ester, an activated
      form of N,N-diethylglycine. Positive patch tests were observed in all the
      patients at 10% in pet., while 20 control patients remained negative. This
      strongly suggests that propacetamol is acting as an activated form of N,N
      diethylglycine, transferring this part of the molecule to nucleophilic residues
      of proteins. This also explains why reactions to acetaminophen have never been
      observed in patients sensitized to propacetamol.

PMID- 9565290
TI  - Application of a 4-h human patch test method for comparative and investigative
      assessment of skin irritation.
AB  - A human 4-h patch test has recently been developed for testing the irritation
      hazard potential of chemicals. The original method was developed for comparative
      irritation assessments relative to benchmark irritants using simple statistical
      tests. In this context, the method has been shown to be robust in intralaboratory
      testing over time. Recent interlaboratory testing has also established the
      consistency of the method in assessment of the relative irritation potential of
      selected chemicals. These data help to position the method as a suitable
      replacement for animal test methods in assessment of skin irritation hazard. In
      addition, the method has great utility for investigating different parameters of
      clinical skin irritation. Using kinetic response patterns and curve fitting
      analysis, we have compared the relative irritation potential of chemicals in
      greater detail, using as a basis the time required for test subjects to respond
      as well as the incidence of positive responses. Also, using the response to 20%
      sodium dodecyl sulfate (SDS) as a benchmark, we've been able to examine the
      intersubject variation in clinical skin irritation responses. In general,
      subjects most reactive to 20% SDS, in terms of the exposure time required to
      produce a positive response, were relatively more sensitive to a 2nd irritant
      chemical as well. However, this was not an absolute correlation in that some test
      subjects showed divergent patterns of response. The method was also used to
      compare directly the relative skin reactivity of different populations, based on
      race (Caucasian versus Asian) or on neurosensory skin sensitivity. Our results
      using this acute exposure test method indicate little difference in visually
      assessed skin irritation among these diverse human subpopulations.

PMID- 9565289
TI  - Contact depigmentation caused by an azo dye in alta.
AB  - Alta, a scarlet-red solution used by some Indian women as a cosmetic to colour
      their feet, was found to be associated with depigmentation at the site of
      application. Chromatographic and spectroscopic analysis of 3 brands of alta
      confirmed the presence of 2 dyes: Crocein Scarlet MOO (CSM) (brilliant crocein)
      and rhodamine B (tetraethyl rhodamine). Patch testing produced depigmentation at
      the site of application of alta, CSM and para-phenylenediamine (PPD). Although
      PPD has been reported to produce leukoderma, azo dyes have not previously been
      reported as depigmenting agents.

PMID- 9565291
TI  - Foot dermatitis in children: causative allergens and follow-up.
AB  - Allergic contact dermatitis from shoes may have a typical pattern of
      presentation, but we have found that the distribution of dermatitis is often
      unhelpful in establishing the diagnosis. In this study, we aimed to define the
      features of foot dermatitis in children and to assess its outcome, in comparison
      to adults with foot eruptions. Relevant allergens were found in 15 out of 29
      children and 26 out of 57 adults with foot eruptions. The most common allergens
      in children were rubber chemicals and topical medicaments. Adults showed a
      similar pattern, but also reacted to clothing dyes. The prognosis in both groups
      was good, with the dermatitis improving or resolving in 2/3.

PMID- 9565292
TI  - Comparison of simultaneous patch testing with parthenolide and sesquiterpene
      lactone mix.
AB  - Several studies have pointed out that the sesquiterpene lactone (SL) mix is a
      safe, though inadequate, screen for Compositae allergy. To test the usefulness of
      the sesquiterpene lactone parthenolide as a supplementary Compositae screening
      test to the mix, both were included in the standard series in 2 Danish
      dermatology departments. Among 2244 patients tested, 46 (2%) were positive to SL
      mix and 73-75% of these were positive to parthenolide. The results demonstrate
      that parthenolide is not suitable as a supplementary screening agent to SL mix,
      but may be a fairly good screen on its own if the mix is not available.

PMID- 9565293
TI  - Genotype and phenotype of N-acetyltransferase 2 (NAT2) polymorphism in patients
      with contact allergy.
AB  - We investigated whether patients with contact allergy differed from non-contact
      allergic, non-atopic controls with regard to genotype and phenotype of the
      polymorphic enzyme N-acetyltransferase 2 (NAT2). 55 contact-allergic patients
      recruited from the Information Network of Departments of Dermatology (IVDK) were
      compared to 85 controls from among local health care personnel. NAT2 activity was
      calculated from HPLC analysis of the ratio of the caffeine metabolites 5
      acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX) in the
      urine. NAT2 genotype was determined by polymerase chain reaction (PCR). A
      statistically significantly increased proportion of rapid acetylators was found
      in contact-allergic patients. This may have 2 possible implications: acetylation
      may enhance contact sensitization; or NAT2 status may be a genetic marker for
      contact sensitizability.

PMID- 9565294
TI  - Hearing aid dermatitis: a study in 20 consecutive patients.

PMID- 9565295
TI  - Narrow spectrum of cross-sensitization with pyridine derivatives.

PMID- 9565296
TI  - Occupational contact dermatitis from methyl-ter-pyridine in a chemistry
      laboratory technician.

PMID- 9565297
TI  - Severe oral and facial reaction to 6 metals in restorative dentistry.

PMID- 9565298
TI  - The so-called contact dermatoses.

PMID- 9565299
TI  - Bank clerk's occupational allergic nickel and cobalt contact dermatitis from
      coins.

PMID- 9565300
TI  - Persistent reactions after patch testing with TRUE Test panels 1 and 2.

PMID- 9565301
TI  - Bullous erythema multiforme following topical diphenylcyclopropenone application.

PMID- 9565302
TI  - Multicentre patch test studies: are they worth the effort?

PMID- 9565303
TI  - Bowlers' grip.

PMID- 9565304
TI  - Clothing dye dermatitis of the scrotum.

PMID- 9565305
TI  - Occupational contact dermatitis from arsenic in a tin-smelting factory.

PMID- 9565306
TI  - Corticosteroid contact allergy in Hungary.

PMID- 9565307
TI  - Thermal contact dermatitis.

PMID- 9565308
TI  - Sensitization to ethyl chloride in a handball player.

PMID- 9565309
TI  - Piroxicam-beta-cyclodextrin and photosensitivity reactions.

PMID- 9565310
TI  - Frequency and determinants of occupational contact dermatitis in 2793
      consecutively-investigated patients.

PMID- 9565311
TI  - Allergic contact dermatitis from para-nitrobenzyl bromide.

PMID- 9565312
TI  - Allergic contact dermatitis due to ethyl alcohol.

PMID- 9565313
TI  - Let Rip! Fun Pot dermatitis.

PMID- 9565314
TI  - Allergic contact dermatitis due to phenol-formaldehyde resin and benzoyl peroxide
      in swimming goggles.

PMID- 9565315
TI  - Allergic contact dermatitis due to panthenol.

PMID- 9565316
TI  - Allergic contact dermatitis from ethoxymethylenemalononitrile in an agrochemical
      chemist.

PMID- 9565317
TI  - Pyoderma gangrenosum secondary to allergic contact dermatitis from rubber.

PMID- 9565318
TI  - Cortical perineuronal nets in the gray short-tailed opossum (Monodelphis
      domestica): a distribution pattern contrasting with that shown in placental
      mammals.
AB  - Extracellular matrix proteoglycans accumulated in perineuronal nets and in
      certain neuropil zones have been shown to influence the immediate neuronal
      microenvironment, and to contribute to the chemoarchitectonic characteristics of
      neuronal networks. Studies in different placental mammals, including the human,
      have suggested that the major principles of extracellular matrix distribution
      remained constant during phylogenesis of the different mammalian strains.
      However, the comparison of matrix distribution between various species also
      indicates that striking deviations from the basic pattern may occur, although
      their functional significance appears unknown as yet. This study examines the
      extracellular matrix in the forebrain of a basic American marsupial, which has
      evolved independently of placental mammals for more than 100 million years. Brain
      sections obtained from adult gray short-tailed opossums (Monodelphis domestica)
      were stained for extracellular matrix components using the N-acetylgalactosamine
      binding lectin Wisteria floribunda agglutinin (WFA), a polyclonal antibody
      against chondroitin sulfate proteoglycans (CSPG), and biotinylated hyaluronectin
      for the detection of hyaluronan. In subcortical regions, the distribution
      patterns of WFA-stained and CSPG-immunoreactive perineuronal nets were similar to
      those reported previously in placental mammals. In contrast, a unique
      distribution was found in the neocortex. This distribution was characterized by
      the presence of perineuronal nets around pyramidal cells and matrix components
      within the adjacent neuropil that together form a continuously labeled zone in
      layer V. Weakly stained nets ensheathed less numerous pyramidal cells in the
      upper layers II/III and a few multipolar cortical neurons. Dual staining
      experiments showed that cortical net-associated neurons were rarely
      immunopositive for parvalbumin. This fact, in addition to the predominant
      association of extracellular matrix components with layer V pyramidal cells,
      differentiates the neocortex in Monodelphis from that of all placental mammals
      studied to date. Regarding the basic phylogenetic position of this marsupial
      species it remains to be shown if these distribution characteristics of
      extracellular matrix may represent also a basic feature of cortical organization.

PMID- 9565319
TI  - Spatial arrangement of fetal placental capillaries in terminal villi: a study
      using confocal microscopy.
AB  - The spatial arrangement of capillaries was studied in terminal villi of placentas
      at term by using confocal microscopy and methods for different types of 3-D
      reconstructions. Fixed specimens embedded in paraffin or glycol methacrylate
      resin were cut and stained with eosin. Digitized images of serial optical
      sections (approximately 0.5 microm) of individual terminal villi lying completely
      inside physical sections (100 microm) were captured by confocal laser scanning
      microscopy and analyzed. Topological reconstruction of the capillary bed and
      measurements of its Euler number, surface and volume rendering and wire-frame
      visualization were performed. Our findings showed that villous capillaries are
      arranged either in a single loop or in a more or less complicated anastomosing
      system. The results suggest that the combination of confocal microscope capture,
      methods for 3-D rendering and characterization of topological features reveals
      valuable information about spatial relationships of tissues in placental villi
      and the arrangement of the villous microcirculation, e.g. about the branching
      pattern of capillaries.

PMID- 9565320
TI  - Distribution and origin of nerve fibers in the rat temporomandibular joint
      capsule.
AB  - The distribution and origin of nerve fibers containing neuropeptides and NOS
      projecting to the temporomandibular joint capsule (TMJ) of the rat were studied
      by retrograde tracing in combination with immunocytochemistry. Numerous nerve
      fibers were seen in the TMJ as revealed by the neuronal marker protein gene
      product 9.5. Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal
      peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), substance
      P (SP), calcitonin gene-related peptide (CGRP), and nitric oxide synthase (NOS)
      were seen in the synovial membrane, the joint capsule and entering the articular
      disc. Injection of the retrograde tracer True Blue (TB) into the TMJ resulted in
      the appearance of numerous labeled nerve cell bodies in the trigeminal and
      superior cervical ganglia, and moderate numbers in the nodose, the otic, the
      sphenopalatine, the stellate and the dorsal root ganglia at levels C2-C5. Most of
      the TB-labeled cell bodies in the superior cervical and stellate ganglia
      contained NPY. In the trigeminal ganglion, numerous TB labeled cell bodies
      contained CGRP and a minor population stored SP, a few cell bodies were seen to
      store NOS or PACAP. In the sphenopalatine and otic ganglia, TB labeled cell
      bodies contained NOS or VIP. In the nodose ganglion, labeled cell bodies
      contained CGRP; other labeled cell bodies harbored NOS. In the cervical dorsal
      root ganglia, the majority of the labeled cell bodies stored CGRP and smaller
      populations stored SP and PACAP. Thus, the innervation of the TMJ is complex and
      many different ganglia are involved.

PMID- 9565321
TI  - An immunohistochemical study of the ontogeny of the neuroendocrine system in the
      chicken oesophagus.
AB  - The ontogenesis and distribution of serotonin-, chromogranin A-, chromogranin B-,
      galanin-, neurotensin-, bombesin- and neuropeptide Y-immunoreactive elements were
      studied in the chicken oesophagus during pre- and post-hatching life. Unlike
      positive nerve elements, that were present in pre- and post-hatching life,
      positive endocrine cells were observed only during embryonic life in the
      oesophageal epithelium. The first endocrine cells, immunoreactive for serotonin
      and chromogranins, appeared on day 12, in the cervical and thoracic portions of
      the oesophagus. At the same age, but only in its distal portion, a few bombesin-
      and neurotensin-immunoreactive cells also appeared. The number of the endocrine
      cells progressively increased, reaching a maximum on day 15. They then decreased,
      with a cranio-caudal progression, until they disappeared a few days after
      hatching. Almost all the serotonin-immunoreactive cells but only a subpopulation
      of bombesin- and neurotensin-immunoreactive cells colocalized chromogranins.
      About half of this subpopulation also colocalized serotonin. All these cells
      reacted positively with Grimelius argyrophile stain. The mucosa of the crop never
      contained positive endocrine cells. Positive nervous elements appeared first in
      the wall of the terminal oesophagus and only one or two days later in the
      proximal oesophagus including the crop. Nervous elements immunoreactive for
      galanin first appeared from days 6 to 7, for neurotensin from days 7 to 8, for
      neuropeptide Y from 13 to 15 and for bombesin from 15 to 18. At day 15 galanin
      immunoreactive ganglionic cells and fibres occupied both the myenteric and
      submucous plexus and galanin-positive nerve fibres could be seen throughout the
      oesophageal wall from the adventitia to a thin subepithelial network. Neurotensin
      and neuropeptide Y-immunopositive ganglionic cells and fibres, by contrast,
      invariably occupied the muscular and submucous layers. Scattered bombesin
      immunoreactive ganglionic cells were observed only in the myenteric plexus. The
      number of positive nerve elements progressively increased until some weeks after
      birth. Density and intensity were always much higher for galanin and neurotensin
      than for neuropeptide Y and bombesin.

PMID- 9565322
TI  - The innervation of the synovium of the knee joint in the guinea pig: an
      immunohistochemical and ultrastructural study.
AB  - The innervation of the knee joint synovial membrane of the guinea pig, i.e., the
      synoviocyte layer, the subjacent connective tissue and the connective tissue
      region beneath, was analyzed with immunohistofluorescence and electron
      microscopy. A screening of the innervation with antibodies against the general
      axon marker -- protein gene product (PGP) 9,5 -- revealed the presence of nerve
      fibers distributed in various regions of the knee joint synovial membrane.
      Confirming previous studies, some of these nerve fibers stained with antibodies
      to tyrosine hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), calcitonin
      gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP). In
      addition, dynorphin (DYN)-containing fibers were detected, which have not been
      reported previously in normal joints. In general, the immunoreactive fibers were
      observed close to the synoviocytes and at blood vessels. Fibers with
      colocalization of NPY- and TH-like immunoreactivities (LIs), as well as of DYN-
      and TH-LIs were demonstrated. In the electron microscope, bundles of unmyelinated
      fibers as well as single fibers were found in the connective tissue region below
      the synoviocytes. Varicose parts of the nerve fibers contained mainly small,
      clear vesicles. Small and large dense-cored vesicles were also seen, but less
      frequently. Denser portions of the plasma membranes of some axons were observed
      in these regions, facing the extracellular space. Myelinated fibers were also
      observed in some nerve bundles. These findings emphasize the complex innervation
      of the synovial membrane, with nerve fibers containing a host of neuroactive
      substances. Altogether, these fibers are probably involved in many functions such
      as vasoregulation and control of synovial secretion in addition to being a source
      of mediators in joint inflammation.

PMID- 9565323
TI  - Ultrastructural localization of lectin binding sites in the developing brain
      microvasculature.
AB  - The temporo-spatial patterning of lectin-binding sites was examined by lectin
      histochemistry and quantitative methods in the microvasculature of the optic
      tectum of 9-, 14-, 20-day-old embryos and 30-day-old chickens. Horseradish
      peroxidase and colloidal-gold-labelled lectins were used for detection of beta-D
      galactose (RCA-I, Ricinus communis agglutinin-I) and of N-acetylglucosamine and
      sialic residues (WGA, Wheat germ agglutinin) at light and electron microscopical
      levels. At the light microscopical level, RCA-I and WGA binding sites were
      detectable in the early embryonic capillaries in a diffuse staining pattern; in
      later embryonic stages and in adult animals, RCA-I labelling became located on
      the abluminal surface of the vessels, while WGA staining was detected on the
      luminal surface. Ultrastructurally, gold labelling for RCA-I was seen
      intracytoplasmically in endothelial cells in 9-day-old embryos. In 14-to 20-day
      old embryos and in chickens, binding sites for RCA-I were detected in endothelial
      tight junctions and basement membranes. In contrast, labelling of the gold
      coupled WGA lectin was distributed almost exclusively on the luminal endothelial
      surface already in early embryos. The results indicate that the endothelial cells
      of the optic tectum acquire functional polarity early in their development and
      that glycoconjugates containing beta-D-galactose residues are involved in the
      biochemical composition of the tight junctions and basement membrane, which are
      considered to be key structures in blood-brain barrier (BBB) differentiation.

PMID- 9565324
TI  - Collagenous fibril texture of the human knee joint menisci.
AB  - Anatomical and clinical literature describes the arrangement of collagen fibrils
      in the human meniscus as being "arcade-like". The "arcade-like" orientation,
      mainly running in a radial direction in the internal circumference and in a
      circular direction in the external circumference, was found in polarization light
      microscopic studies. This, however, does not provide a mechanical explanation for
      the direction of meniscus tears. In view of this contradiction collagen fibrils
      in the menisci of adults aged from 18 to 85 years were exposed layer-by-layer to
      study their arrangement by scanning electron microscopy. The results obtained by
      this procedure were compared to the path of the split lines. Scanning electron
      microscopy reveals three distinct layers in the meniscus cross section: (1) The
      tibial and femoral sides of the meniscus surfaces are covered by a meshwork of
      thin fibrils with a diameter of approximately 30 nm. (2) Beneath the superficial
      network there is a layer of lamellalike collagen fibril bundles on the tibial and
      femoral surface. In the area of the external circumference of the anterior and
      posterior segments the bundles of collagen fibrils are arranged in a radial
      direction. In all other parts the collagen fibril bundles intersect at various
      angles. (3) The main portion of the meniscus collagen fibrils are located in the
      central region between the femoral and the tibial surface layers. Everywhere in
      the central main portion of the meniscus the bundles of collagen fibrils are
      orientated in a circular manner. The split lines in the region of the internal
      circumference of the menisci are arranged in a circular manner, generally running
      in a radial direction in the portions adjacent to the base. Scanning electron
      microscopy reveals that the direction of the split lines depends on the
      orientation of the collagen fibrils in the superficial lamellar layer. The arcade
      like path of the collagen fibrils described in the literature can not be
      confirmed either by scanning electron microscopy or by the course of the split
      lines. The circular arrangement of collagen fibrils in the central portion of the
      meniscus provides a functional explanation for the longitudinal orientation of
      the majority of tears in the meniscus tissue.

PMID- 9565325
TI  - Pulmonary neuroepithelial bodies are innervated by vagal afferent nerves: an
      investigation with in vivo anterograde DiI tracing and confocal microscopy.
AB  - The pulmonary airway and alveolar epithelia contain distinctly innervated
      clusters of basally granulated cells: the neuroepithelial bodies. In the past,
      morphological criteria and the results of selective vagotomy have led to the
      interpretation that their innervation is sensory. Consequently, they are regarded
      as receptor organs. As a further test of this hypothesis, the present
      investigation set out to label vagal sensory nerve fibres to the lungs by
      anterograde neural tracing, and to establish the relationship between these
      fibres and the neuroepithelial bodies. A fluorescent neural tracer was injected
      unilaterally into the left or right nodose ganglion of adult rats. After suitable
      survival times, thick frozen sections of lung tissue were studied with laser scan
      confocal microscopy. Sensory nerve fibres were seen to run in the airway walls
      and occasionally penetrated the epithelium, where they formed complex terminals.
      The resulting intraepithelial sensory end organs showed a close morphological
      resemblance to the neuroepithelial bodies. Subsequently, electron microscopic
      investigation of such identified structures revealed the typical ultrastructural
      characteristics of neuroepithelial bodies: corpuscular cells containing dense
      cored secretory vesicles and contacted by mitochondria-rich nerve endings. We
      conclude that anterograde tracing of sensory nerves from the nodose ganglion
      confirms the receptor nature of the pulmonary neuroepithelial bodies, which may
      correspond to a subpopulation of the irritant and C-fibre receptors.

PMID- 9565326
TI  - Intercellular and lymphatic pathways associated with tonsils of the soft palate
      in young pigs.
AB  - Tonsils of the soft palate of pigs are the main oropharyngeal lymphoid tissues
      that protect the body against antigens entering through the mouth. The aim of
      this work was to elucidate the intercellular and lymphatic pathways by which
      lymph and cells are transported through these tonsils. Tonsillar tissue from
      freshly-killed pigs was examined using light microscopy and electron microscopy,
      or was injected with Mercox for scanning electron microscopy of corrosion casts.
      Intercellular fluid passes between epithelial cells and is continuous with that
      of the subepithelium. Fluid from the subepithelium flows into sinuses that form a
      network around the apex of follicles. These sinuses are continuous with
      parafollicular sinuses that penetrate the parafollicular tissue between the
      follicles. Some parafollicular sinuses are traversed by a complex network of cell
      processes, whereas others appear to lack such processes. Some parafollicular
      sinuses are closely located (10 microm) to venules; others lie adjacent to the
      follicle capsule. No lymphatics enter or leave the follicles. All lymph from the
      tonsils must traverse parafollicular sinuses before entering septal vessels, and
      these are continuous with basal vessels. Basal vessels coalesce to form efferent
      vessels that transport lymph from the tonsil to the primary lymph nodes. Septal,
      basal and efferent lymphatic vessels contain prominent valves and many
      lymphocytes. Lymphatic sinuses appear to be a significant pathway for lymphocytes
      migrating from the tonsillar lymphoid tissue.

PMID- 9565327
TI  - Enzyme immunoassay for cholesteryl ester transfer protein in human serum.
AB  - We developed a new simple sandwich-type enzyme immunoassay to measure cholesteryl
      ester transfer protein (CETP) mass in human serum. In assay validation, Intra-
      and Inter-assay coefficients of variation were 2.7 to 5.7% and 2.2 to 12.2%,
      respectively. There was no cross-reactivity with various lipoproteins (apo A-I,
      apo A-II, apo B, apo C-III). A good correlation between CETP mass and CETP
      activity (n = 46, correlation coefficient = 0.88) was observed. This assay
      provided a specific and reproducible method for measuring CETP mass in samples.
      The average value of CETP in the normal sera of 41 males was 1.8+/-0.6 microg/ml
      (mean+/-S.D.) and that of 37 females was 2.0+/-0.5 microg/ml. In the study of
      patients with the CETP gene mutation (Int 14A and D442G), our results on the
      value of plasma CETP mass reflected to genetic CETP deficiency. In conclusion,
      this assay for CETP mass in human serum may be a useful tool for clinical
      investigations involving lipid metabolism related to disease.

PMID- 9565328
TI  - Comparative analysis of Epstein-Barr virus (EBV) detection by nested-PCR and non
      isotopic in situ hybridization in nasopharyngeal carcinoma (NPC).
AB  - The aims of this study were two-fold: first, to assess the relative diagnostic
      performance of non-isotopic in situ hybridization (ISH) and the nested polymerase
      chain reaction (nested-PCR) applied to Epstein-Barr virus (EBV) detection in a
      series of 55 unselected nasopharyngeal carcinoma (NPC) cases and, secondly, to
      correlate these data with histopathological classification. Our study shows that
      in 76.36% of NPC cases positive nuclear signals were observed using EBV-ISH.
      Overall, EBV-ISH positivity varied according to histological type, in that
      undifferentiated carcinomas showed a higher proportion of positive cases than
      differentiated cell carcinomas, although ISH results do not show significant
      differences in relation to histological types when employing two different
      schemes (WHO and Micheau). However, in adequate quality DNA samples (54 NPC
      cases), EBV-DNA was detected in 100% of cases using a nested-PCR, supporting the
      previous view that all histological types of NPC are in reality variants of EBV
      infected neoplasia. ISH-negative cases probably reflect a lower sensitivity than
      PCR, particularly when a small number of viral copies are present, as well as a
      variable technical effectiveness for detected EBV, independent of the NPC
      histological type.

PMID- 9565329
TI  - A fluorescence method for estimation of toxemia: binding capacity of lipoproteins
      and albumin in plasma.
AB  - The hazard of toxemia, a condition resulting from the spread of toxins by the
      bloodstream, is regulated by plasma proteins capable of binding with free toxins.
      As toxin binding results in a reduction of available binding sites, measuring the
      proteins' binding capacity can be used to estimate toxemia severity. Suggested by
      this approach, a novel fluorescence method was developed to determine lipoprotein
      and albumin binding capacities in whole plasma. The method entails two steps:
      specific binding of N(n-carboxy)phenylimide-4-dimethyl-aminonaphthalic acid with
      albumin followed by addition of 12-(9-anthroyloxy)stearic acid which, under these
      conditions, binds mostly with lipoprotein. Reduced fluorescence intensity of the
      probes in plasma of patients compared to that of healthy donors reflected
      saturation of binding sites by toxins, thereby estimating toxemia severity. Poor
      correlation was found between the lipoprotein and albumin binding abilities,
      suggesting their independent diagnostic values. The simplicity and rapidity of
      this method are advantageous for its clinical application.

PMID- 9565330
TI  - Total glycolipid and glucosylceramide content in serum and urine of patients with
      Gaucher's disease type 3 before and after enzyme replacement therapy.
AB  - The follow-up of Gaucher's patients under enzyme replacement therapy is generally
      based both on the clinical aspects and the evaluation of haematological
      parameters: haemoglobin level, platelet count, acid and alkaline phosphatase
      activities. Spleen and liver volumes are also reliable criteria for evaluating
      the improvement of the patients. The determination of glycolipid excretion in the
      urine and/or the quantification of glycolipids in serum can also be a useful tool
      for the screening and the follow up of patients with lysosomal storage disease
      including Gaucher's disease. In this paper we report the follow-up of three
      patients with Gaucher type 3; in order to test the efficacy of the enzyme
      replacement therapy with alglucerase in these patients, we evaluated the urine
      and plasma glucosylceramide content as a marker parallel to the clinical
      improvement and the decreased organomegaly.

PMID- 9565331
TI  - Serum activities of classes I and II alcohol dehydrogenases in toxic liver
      damage.
AB  - The activities of classes I and II alcohol dehydrogenase isoenzymes were
      determined in the sera of patients with toxic hepatitis using class-specific
      fluorogenic substrates. The activities of total alcohol dehydrogenase and enzymes
      indicative of liver damage were also measured. We found a statistically
      significant increase of class I alcohol dehydrogenase isoenzymes. The increase in
      class I (two-fold) was similar to the increase of alkaline phosphatase. In a
      correlated study, we observed a good correlation of the activity of class II
      isoenzymes with alanine aminotransferase. The total alcohol dehydrogenase
      activity was enhanced and correlated with lactate dehydrogenase. These results
      demonstrated that the alcohol dehydrogenase and class I isoenzymes are indicatory
      enzymes of liver cell damage, and may be diagnostically useful in toxic
      hepatitis.

PMID- 9565332
TI  - Activities of proteases in parietal thrombus of aortic aneurysm.
AB  - Deterioration of the aortic wall resulting in formation of aneurysm may be evoked
      by increased activity of elastases, collagenases and lysosomal proteases. These
      enzymes come from macrophages and neutrophil granulocytes which are elements of
      the inflammatory reaction accompanying aneurysm. These cells may also come from
      parietal thrombus in the aneurysm lumen. The aim of this work was to determine
      activity of elastase, cathepsin G, collagenase-like Pz-peptidase and cathepsins
      A, B, C, D and E in the parietal thrombus of aortic aneurysm. The thrombus was
      obtained from the lumen of the aortic aneurysm of six patients during operation.
      Protease activities were determined using specific substrates at optimum pH.
      Retracted blood clot was a comparative material. The thrombus of aortic aneurysm
      showed two-five fold higher activity of elastases, collagenase-like Pz-peptidase
      and cathepsins A, D and G in comparison to the blood clot (P < 0.001). However,
      activity of cathepsins B, C and E in the thrombus was only slightly higher (P <
      0.05). Prolonged effect of proteases coming from parietal thrombus on the
      aneurysm wall could evoke marked degradation of fibrillar proteins resulting in
      increase of aneurysm.

PMID- 9565333
TI  - Beneficial effect on serum apo AI, apo B and Lp AI levels of Ramadan fasting.
AB  - In order to investigate for the first time in Morocco the effect of fasting in
      Ramadan, the ninth lunar month of the muslim year, on lipoprotein metabolism, we
      determined the levels of serum apolipoproteins; apolipoprotein AI (apo AI), apo
      B, apo AIV and those of lipoprotein particles; apo AI-containing lipoprotein
      particles (Lp AI) and also apo AI and apo AII containing lipoprotein particles
      (Lp AI:AII) in a group of 32 healthy, volunteer adult males. Determination of all
      these parameters was carried out on each week of the month of Ramadan and the
      results are compared with the pre-fasting and the post-fasting values. Ramadan
      fasting reduces significantly serum apo B (P < 0.05), while serum apo AI is
      significantly increased (P < 0.05) compared with the pre-fasting period. The
      increase of apo AI occurred on day 29 of Ramadan by 11.8%. Serum apo AIV was
      unchanged during the fasting period indicating that food intake during Ramadan is
      not based on lipid diet. The observed diet pattern during Ramadan showed an
      increase of total energy intake based on carbohydrates (+1.4% of total energy),
      proteins (+0.4% of total energy) but not on fat (-0.7% of total energy), compared
      with a usual diet used in the rest of the year. The fat diet is high in
      monounsaturated (P < 0.05) and polyunsaturated fatty acid in contrast to
      saturated fatty acid which decreased (P < 0.05) during Ramadan. On the other
      hand, analysis of serum Lp AI and Lp AI:AII showed that the levels of Lp AI:AII
      were unchanged but those of Lp AI were significantly increased (P < 0.01) at the
      end of Ramadan. These findings show that feeding behaviour that occurs during
      Ramadan beneficially affects serum apolipoprotein metabolism and may contribute
      to prevention of cardiovascular diseases.

PMID- 9565334
TI  - Breast cancer progression is associated with a reduction in the diversity of
      sialylated and neutral oligosaccharides.
AB  - Changes in the oligosaccharides attached to glycoproteins and glycolipids have
      been observed in a variety of malignancies. To understand the relationship
      between oligosaccharide expression and breast cancer progression we extracted and
      mapped the sialylated and neutral oligosaccharides from primary breast tumours of
      patients treated between 1979 and 1981 at Middlesex and University College
      Hospitals, London. Tumours from two patient groups were evaluated as short-term
      and long-term survivors. Short-term survivors developed widespread disease within
      five years (n = 10) whereas long-term survivors had no sign of cancer after
      fifteen years (n = 9). Paraffin-wax embedded breast cancer specimens were
      microdissected, the oligosaccharides were released and mapped by separation on
      anion-exchange and gel permeation chromatography columns. A decrease in the
      diversity of sialylated and neutral oligosaccharides and the number of sialylated
      structures was observed in aggressive breast cancers. Aggressive cancers had
      elevated levels of a mono- and tri-sialylated oligosaccharide only found in trace
      levels in non-aggressive cancers.

PMID- 9565335
TI  - Characterization of phytanoyl-Coenzyme A hydroxylase in human liver and activity
      measurements in patients with peroxisomal disorders.
AB  - Phytanoyl-Coenzyme A hydroxylase is a newly recognized peroxisomal enzyme which
      catalyses the first step in the alpha-oxidation of phytanoyl-Coenzyme A. Since
      measurement of this enzyme activity in human liver homogenate is of great
      importance especially in relation to inherited diseases in which this enzyme
      activity is deficient, we have studied its characteristics in human liver. The
      results described in this paper show that optimal activity measurements require
      preformed phytanoyl-Coenzyme A plus 2-oxoglutarate, Fe2+ and ascorbate. The
      conditions developed can be used to determine phytanoyl-Coenzyme A hydroxylase
      activity in human liver homogenates which is of utmost importance not only for
      the diagnosis of patients, but also for the purification of the enzyme from
      various sources.

PMID- 9565336
TI  - Persistently raised serum acid phosphatase activity in a patient with
      hypophosphatasia: electrophoretic and molecular weight characterisation as type
      5.
AB  - Hypophosphatasia is a rare disorder characterised by low levels of serum alkaline
      phosphatase activity resulting in abnormal phosphorylated metabolites and varying
      skeletal abnormality. We have followed a patient with adult type hypophosphatasia
      for over ten years who has also shown a persistently elevated tartrate resistant
      acid phosphatase activity (TRAP) without any obvious cause. Characterisation of
      this TRAP by polyacrylamide gel electrophoresis (pH 4.0) showed migration to band
      5 position. Molecular weight determination by FPLC and an estimate of the
      molecular weight by gradient gel electrophoresis gave a molecular weight of
      29,000-43,600. This molecular weight makes it unlikely for this to be a IgG/TRAP
      complex persisting in the circulation. Paranitrophenylphosphate was the preferred
      substrate. This characterises the enzyme as type 5 acid phosphatase which is of
      the mononuclear/phagocyte type, possibility of osteoclastic origin, though the
      tissue source remains unknown.

PMID- 9565337
TI  - International Society of Andrology and International Union of Pure and Applied
      Chemistry, Clinical Chemistry Section, Commission on Nomenclature, and
      International Federation of Clinical Chemistry Scientific Division. Properties
      and units in the clinical laboratory sciences XIII. Properties and units in
      reproduction and fertility (IUPAC-IFCC technical report 1998).
AB  - This document is the first recommendation on the presentation of properties in
      reproduction and fertility and their values in clinical laboratory sciences from
      The International Society of Andrology, IFCC and IUPAC. It forms part of the
      ongoing effort to standardise requests and reporting of laboratory data for
      transmission across cultural and linguistic domains, without attempting to
      standardise the language used by clinicians and laboratory practitioners. The
      document is accessible on Internet from C-NPU home page address: http://inet.uni
      c.dk/ home/ifcc_iupac_cnpu.

PMID- 9565338
TI  - Carcinomas of the breast showing myoepithelial cell differentiation. A review of
      the literature.
AB  - Myoepithelial cells are normally located between the epithelial cells and the
      basal lamina of secretory elements of exocrine glands. Their role in the
      histogenesis of breast tumours has been studied extensively, and a definite
      differentiation towards myoepithelial cells has been demonstrated in adenoid
      cystic carcinoma, adenomyoepithelioma, low-grade adenosquamous (syringomatous)
      carcinoma, pure malignant myoepithelioma and poorly differentiated myoepithelial
      rich breast carcinoma. All these tumours are of low malignancy, with the
      exception of malignant myoepithelioma and poorly differentiated myoepithelial
      rich carcinoma. When a low-grade tumour is associated with a spindle cell
      component, distant metastases must be expected. Pure malignant myoepithelioma
      shows morphological and clinical features similar to those of monophasic
      sarcomatoid carcinomas, and it is possible that this last tumour is linked
      histogenetically to sarcomatoid carcinomas.

PMID- 9565339
TI  - Gastric carcinoma risk index in patients infected with Helicobacter pylori.
AB  - Epidemiological data show an association between Helicobacter pylori gastritis
      and gastric carcinoma. However, most people infected with H. pylori do not
      develop gastric cancer. We have therefore evaluated histological criteria
      indicating an increased risk for gastric cancer. H. pylori gastritis was
      investigated in 117 patients with small (O<2 cm) early gastric carcinomas and in
      117 age-matched duodenal ulcer patients infected with H. pylori, who are known to
      have a low risk for developing gastric carcinoma. The results showed that
      infiltration with lymphocytes/plasma cells and infiltration with neutrophils
      predominating in the corpus, and intestinal metaplasia in antrum and corpus were
      associated with both types of gastric carcinoma (intestinal and diffuse,
      P<0.0001). If an index is computed by giving one point to each of these features,
      the predictive value for the presence of gastric carcinoma was 0.79 with a score
      of 2, and 0.94 with a score of 3 (all points on the index used). Application of
      this index might be a simple method of identifying patients infected with H.
      pylori and carrying a higher risk for gastric carcinoma.

PMID- 9565340
TI  - A new view of the so-called adenoma malignum of the uterine cervix.
AB  - Adenoma malignum of the uterine cervix (mucinous type of minimal deviation
      adenocarcinoma, mucinous MDA), is a unique neoplasm that is difficult to diagnose
      owing to the deceptively benign appearance of the tumour cells. The present study
      was undertaken to explore the phenotypic expression of this tumour compared with
      those of non-neoplastic cervical tissues and of cervical carcinomas of various
      types. Ten cases of mucinous MDA, 50 cases with non-neoplastic cervical tissues,
      13 of cervical adenocarcinoma including the mucinous (endocervical or intestinal
      type) and endometrioid types, and 2 of mucoepidermoid carcinoma were examined by
      various histochemical staining methods, including those for gastric mucins,
      pepsinogen, lysozyme, chromogranin A and carcinoembryonic antigen. The results
      revealed that mucinous MDA characteristically exhibited gastric phenotypes. The
      presence of gastric metaplasia was also demonstrated in 9 cases of mucinous MDA
      and in 5 of the other cases examined. The 7 endocervical-type adenocarcinomas
      also included 4 that expressed gastric phenotypes, and 2 of the 3 intestinal-type
      adenocarcinomas showed the same properties focally. These results indicate the
      presence of a group of lesions expressing gastric phenotypes in the uterine
      cervix and suggest a close relationship between these lesions. Cervical
      adenocarcinomas expressing gastric phenotypes are probably derived from MDA.

PMID- 9565341
TI  - Organotypic culture of HPV-transformed keratinocytes: a model for testing
      lymphocyte infiltration of (pre)neoplastic lesions of the uterine cervix.
AB  - The aim of our study was to establish the relevance of an in vitro model for
      analysing the ability of human lymphocytes to infiltrate human papillomavirus
      (HPV)-associated (pre)neoplastic lesions of the uterine cervix. To mimic these
      lesions, we have used the organotypic raft culture of HPV-transformed
      keratinocytes (SiHa). The SiHa organotypic raft culture was co-cultured with
      resting or prestimulated (IL-2 or IL-2+anti-CD3 mAb) allogeneic peripheral blood
      mononuclear cells (PBMC) for 24 and 72 h. The majority of infiltrating cells were
      T lymphocytes. Occasional NK cells were also identified. The stimulation with IL
      2+anti-CD3 mAb induced the highest number of infiltrating cells, with the maximum
      lymphocyte infiltration observed after 24 h of co-culture. The lymphocyte
      infiltration was associated with an increased number of apoptotic cells in the
      organotypic cultures. The ability of PBMC and purified T cell and NK cell
      populations to lyse HPV-transformed keratinocytes was also investigated on
      monolayer cultures. As expected in an allogenic model, the highest cytotoxicity
      was mediated by NK cells activated by IL-2 or IL-2+anti-CD3 mAb. The cytotoxic
      activity of T cells was weak but, interestingly, increased in the presence of
      phytohaemagglutinin A (PHA), assuming that T cells were able to kill HPV-infected
      keratinocytes when a bridge between T cells and keratinocytes was provided. In
      conclusion, the organotypic culture of HPV-transformed keratinocytes may provide
      an effective in vitro model for investigating novel T cell-based immunotherapy
      protocols for the treatment of HPV-associated lesions.

PMID- 9565342
TI  - Expression of c-Met in laryngeal carcinoma.
AB  - Expression of c-Met, a gene for the hepatocyte growth factor/scatter factor
      (HGF/SF) receptor, is known to be associated with tumour development in several
      human carcinomas. The expression of c-Met was examined using immunohistochemistry
      in 82 cases of primary laryngeal carcinoma to evaluate the tissue distribution of
      c-Met and the clinicopathological significance of c-Met expression. In normal
      larynx, c-Met expression was observed only in some minor salivary glands.
      Positive reaction for c-Met in neoplastic epithelium was noted in 45 out of 82
      (54.9%) cases. In 44 cases, structures adjacent to the carcinoma (noncancerous
      squamous epithelium, some stromal fibroblastic cells, and endothelial cells)
      showed positive reaction for c-Met. c-Met expression in cancerous epithelium was
      significantly correlated with lymph node status (P<0.04) and proliferating
      activity expressed by the Ki-67 labelling index (P<0.02). There was no
      correlation between c-Met expression and age, sex, histological type, T category,
      distant metastasis or clinical stage. The data suggest that overexpression of c
      Met in laryngeal carcinomas represents a growth advantage for cancer cells, which
      may be conferred by the mitogenic effect of HGF/SF. Simultaneous c-Met expression
      in noncancerous components of the larynx may represent a paracrine modification
      of c-Met.

PMID- 9565343
TI  - Expression of c-Met receptor and hepatocyte growth factor/scatter factor in
      synovial sarcoma and epithelioid sarcoma.
AB  - Overexpression of c-Met receptor/hepatocyte growth factor (scatter factor) system
      (c-Met/HGF/SF) as a physiologically paracrine cellular signaling system is
      thought to be involved in the progression of malignant tumours. In 26 synovial
      sarcomas and epithelioid sarcomas, c-Met and HGF/SF expression was analysed
      immunohistochemically. There were 10 biphasic synovial sarcomas, 7 of which
      showed moderate to strong c-Met expression in epithelial areas compared with the
      fibrous component, with corresponding expression of HGF/SF. Six of 9 monophasic
      fibrous synovial sarcomas showed only very faint c-Met and corresponding HGF/SF
      expression. In 7 epithelioid sarcomas strong expression of c-Met and HGF/SF was
      observed within epithelioid tumour cells. Non-radioactive in situ hybridization
      demonstrated the synthesis of c-Met receptor in tumor cells by detecting c-met
      mRNA. This analysis shows that in synovial sarcomas and epithelioid sarcomas,
      tumour entities with epithelial and mesenchymal structures, c-Met and HGF/SF
      overexpression can be detected, indicating a role of this signaling system in
      these subtypes of sarcoma, and especially in the more epithelioid tumour
      phenotype. An autocrine interaction between overexpressed c-Met receptor and
      HGF/SF may be hypothesized.

PMID- 9565344
TI  - Staining pattern of seven monoclonal anti-CD26 antibodies in leprosy:
      implications for the use of CD26 as a surrogate marker of a human Th1-like
      reaction.
AB  - In a previous study using the monoclonal anti-CD26 antibody MIB-DS2/7 in leprosy
      and other granulomatous diseases, it was shown that CD26 may be a candidate for
      use as an operational marker of a human Th1-like reaction. In this follow-up
      study, we compared seven different monoclonal anti-CD26 antibodies with respect
      to their staining pattern in lepromatous and tuberculoid leprosy tissues. Three
      distinct staining patterns became apparent in this anti-CD26 antibody panel:
      staining of T-lymphocytes and of connective tissue; staining of T-lymphocytes,
      connective tissue and macrophages; and almost no staining of T-lymphocytes but
      staining of connective tissue and macrophages. The two antibodies assigned to the
      first staining pattern, including MIB-DS2/7, were found to be most suitable for
      the operational discrimination between Th1-like and Th2-like reactions in
      leprosy. The antibodies assigned to staining patterns 2 and 3 did not allow this
      discrimination. Although all seven monoclonal antibodies investigated were
      specific for CD26, only two were found to be useful in identifying a Th1-like
      immune reaction in human tissue.

PMID- 9565345
TI  - Defects of the respiratory chain in hepatic oncocytes.
AB  - Oxyphilic hepatocytes, also called hepatic oncocytes, have been found in 20 of 47
      cirrhotic livers (42%) with defects of the respiratory chain. Immunohistochemical
      studies using antisera against cytochrome-c-oxidase (complex IV) revealed
      respiratory chain-deficient oxyphilic foci in 16 of the 20 cases (75%). Fourteen
      percent of the oxyphilic areas were deficient, whereas only 8.5% of the
      nonoxyphilic liver nodules showed respiratory chain defects (P < 0.004). In
      addition, oxyphilic foci made up about 18% of all defective areas but were
      present in only 11.5% of the regenerative nodules. These results illustrate that
      oxyphilic cell change is associated with a higher propensity for the development
      of respiratory chain defects, but is not obligatory for this.

PMID- 9565346
TI  - Thymic myoid cell turnover in myasthenia gravis patients and in normal controls.
AB  - Thymic myoid cells (TMC) are sparse muscle-like cells in the thymic medulla,
      which are believed to trigger the autoimmune response in myasthenia gravis (MG).
      Ultrastructural investigations have revealed mature, degenerating, and immature
      TMC, but the number of TMC in MG patients does not differ from that in controls.
      We examined the turnover of TMC at the subcellular level, performing an
      immunocytochemical study with muscle-specific anti-desmin labelling of 10
      thymuses derived from MG patients with lymphofollicular hyperplasia and from 8
      normal controls. All thymuses examined revealed mature, immature, and
      degenerating TMC. Mature TMC contained desmin filaments in between Z-discs
      provided the sarcomeres were arranged in register. Morphological features of
      degenerating TMC included hypercontracted sarcomeres, cytoplasmic granular
      debris, chromatin clumping and, occasionally, membrane-bound bodies. Macrophages
      were not involved in the process. Immature TMC were of small diameter and
      contained myofilaments not arranged in myofibrils. In an MG thymus, small
      immature TMC were found clustered with dying TMC. It may be that degeneration of
      TMC is a stimulus for the generation of new TMC with faster turnover. This
      mechanism may mean that more antigen is available in MG patients than in normal
      controls, despite constant TMC numbers.

PMID- 9565347
TI  - Cutaneous nerves in atopic dermatitis. A histological, immunohistochemical and
      electron microscopic study.
AB  - Although pruritus is the cardinal symptom of atopic dermatitis, its mechanism is
      not well understood. Free nerve endings in the skin are involved in pruritus as
      itching receptors. We studied the cutaneous nerve fibres in lichenified lesions
      of 16 patients with adult atopic dermatitis. On immunohistochemistry, fibres
      immunoreactive for neurofilament, neuron-specific enolase, and protein gene
      product 9.5 were observed in the papillary dermis and dermoepidermal junctions as
      well as in the epidermis. In these areas, no fibres stained positively for
      substance P, neuropeptide Y, vasoactive intestinal peptide, beta endorphin,
      somatostatin or serotonin. On electron microscopy, the ultrastructure of
      subepidermal and intraepidermal free nerve endings appeared to be essentially
      normal. However, the distribution density of the cutaneous nerve fibres was much
      higher than in normal controls, and the diameter of these fibres was much larger,
      because of the large number of axons in each nerve fibre. Degranulation of mast
      cells was not seen. These findings suggest that pruritus in lichenified atopic
      skin is probably not caused by damage to the cutaneous free nerve endings. In
      such lesions, the number of the cutaneous free nerve endings is greatly
      increased, but they may have a normal function.

PMID- 9565348
TI  - Gastrin stimulates epithelial cell proliferation in the oesophagus of rats.
AB  - Gastrin can induce mitotic stimulation in the oxyntic mucosa of the stomach,
      sometimes leading to abnormal growth. We examined whether gastrin was able to
      influence cell proliferation in the oesophageal epithelium. Rats were treated
      with gastrin, omeprazole or saline for 3 days, or were subjected to fundectomy or
      sham operation. Bromodeoxyuridine labelling (LI) and mitotic (MI) indices were
      counted in the proliferative zone of the squamous epithelium. Infusion of
      exogenous gastrin, treatment with omeprazole or fundectomy raised the LI and the
      MI values in the oesophageal epithelium, indicating that gastrin stimulates cell
      proliferation in the oesophageal mucosa in the rat.

PMID- 9565349
TI  - Poorly differentiated desmin-negative and vimentin-positive leiomyosarcoma of the
      stomach examined by the immunohistochemical and quick-freezing and deep-etching
      methods.
AB  - A poorly differentiated leiomyosarcoma of the stomach in a 41-year-old woman is
      reported. The diagnosis was confirmed by the diffuse immunohistochemical reaction
      to HHF35, and the presence of focal density and caveolas in some of the tumour
      cells by conventional electron microscopy. Immunohistochemically, most tumour
      cells had an undifferentiated nature, in which negative immunostaining for
      desmin, alpha-smooth muscle actin, and type IV collagen, and positive
      immunostaining for vimentin were observed. By the quick-freezing and deep-etching
      (QF-DE) method, these tumour cells revealed the loss of bundled actin and myosin
      filaments, which constitute desmin associated structures (focal densities and
      dense patchy areas). Their cytoplasm had many mitochondria and other cell
      organelles. The intermediate filaments (IFs), which were determined to be
      vimentin by immunohistochemistry, were observed in the inter-organellar spaces,
      and connected with these cell organelles. Actin filaments formed a meshwork
      structure and were distributed mainly in subplasmalemmal regions. Although a
      basal lamina was not detected by conventional electron microscopy, basal lamina
      like structures, an association between the extracellular matrices and the cell
      membrane, were observed. Using the QF-DE method, three dimensional
      ultrastructural alterations of the cytoskeleton and extracellular matrix of the
      leiomyosarcoma were observed.

PMID- 9565350
TI  - Ductal adenocarcinoma of the pancreas in MEN-1-patients.

PMID- 9565351
TI  - Functional analysis of CD82 in the early phase of T cell activation: roles in
      cell adhesion and signal transduction.
AB  - To define T cell co-stimulatory molecules that work in the early phase of T cell
      activation, we established monoclonal antibodies (mAb) that inhibit or enhance T
      cell activation by the histiocytic leukemia cell line U937. One of the mAb, 53H5,
      which recognized both T cells and U937, was identified to bind to CD82 by
      expression cloning. Functional analyses of CD82 revealed that 1) CD82 needs to
      exist on both T cells and U937 for the full activation of T cells; 2) CD82
      expression is up-regulated on both T cells and U937 by stimulation such as CD3
      ligation or treatment with phorbol 12-myristate 13-acetate; 3) overexpression of
      CD82 enhances both homotypic and heterotypic cell adhesion between T cells and
      U937; 4) CD82 signal co-stimulates T cells and the signal works synergistically
      with the CD28-mediated T cell co-stimulation signal; 5) in mixed leukocyte
      reactions using U937 as stimulator cells, CD82 overexpression on U937 correlates
      with the higher allogeneicity of U937 cells. These results indicate that CD82 co
      stimulates T cells not only by sending intra-T cell signals that work
      synergistically with CD28 signals but also by inducing enhanced T cell-antigen
      presenting cell interaction.

PMID- 9565352
TI  - C-type lectin-like receptors in peptide-specific HLA class I-restricted cytotoxic
      T lymphocytes: differential expression and modulation of effector functions in
      clones sharing identical TCR structure and epitope specificity.
AB  - C-type lectin-like inhibitory receptors are heterodimers consisting of CD94 and
      NKG2-A-B molecules expressed on NK cells and on a subset of activated T
      lymphocytes. Their inhibitory effects on NK cytotoxicity and on the NK-like
      activity of T cell clones have been demonstrated, but no data are currently
      available on antigen-specific class I-restricted cytotoxic T lymphocytes (CTL).
      We have generated a panel of HLA-A2.1-restricted CTL clones directed against a
      nonapeptide derived from a melanoma-associated antigen, dopachrome tautomerase
      (TRP-2). All clones were CD8+ and TCR alphabeta+. About half of them expressed a
      CD94bright phenotype, whereas the remaining were CD94dim. Only the CD94bright CTL
      expressed the NKG2-A-B gene, consistent with the expression of a C-type, lectin
      like, inhibitory CD94/NKG2-A-B heterodimer. Both CD94bright and CD94dim clones
      appeared to require similar amounts of synthetic epitope sensitizing target
      cells. Addition of anti-CD94 mAb resulted in a significant increase of specific
      killing by CD94bright, but not by CD94dim clones in the presence of suboptimal
      concentrations of peptide, whereas, when optimal amounts were used, the mAb did
      not induce a significant modulation of the cytotoxicity. Antigen-induced inward
      [Ca2+]i fluxes were unaffected, but an enhancement of TCR down-modulation could
      be observed in the presence of anti-CD94 mAb at high concentration of antigenic
      peptide. The analysis of the TCR-Vbeta repertoire of the CTL clones by RT-PCR and
      immunofluorescence revealed that all clones regardless of CD94 phenotype shared
      Vbeta22 expression. Most importantly, sequence analysis showed that they all
      expressed identical Vbeta22 TCR rearranged with Jbeta2.1 and Cbeta2. Taken
      together, these data indicate that different expression of functionally active
      lectin-like inhibitory receptors can be detected in CTL clones sharing identical
      TCR sequence and peptide specificity.

PMID- 9565353
TI  - Immunogenicity of the ALLAVGATK (gp100[17-25]) peptide in HLA-A3.1 melanoma
      patients.
AB  - A T cell line recognizing autologous and allogeneic HLA-A3.1 melanomas was
      obtained from a disease-free melanoma patient (patient 15392). By transfection of
      a tumor cDNA library and in vitro sensitization experiments, the ALLAVGATK
      gp100/Mel17-derived peptide was found to be the epitope recognized by this
      melanoma-specific T cell line. The role of the ALLAVGATK peptide in the systemic
      immune response to melanoma of this patient was evaluated. When pulsed on the
      autologous peripheral blood mononuclear cells, the ALLAVGATK peptide generated
      tumor-specific HLA-A3-restricted T lymphocytes and a single restimulation in
      vitro was sufficient to raise gp100-specific T lymphocytes, indicating a high
      frequency of epitope-specific T cells. gp100-specific T cells were also induced
      from T lymphocytes purified from tumor-invaded lymph nodes (tumor-associated
      lymphocytes, TAL). TAL-derived effectors displayed lower peptide affinity and
      lower tumor recognition than effectors elicited from peripheral blood lymphocytes
      (PBL). To further evaluate its immunogenicity, ALLAVGATK was used to stimulate
      PBL derived from six additional HLA-A3.1 melanoma patients and seven healthy
      donors. After 7 weeks of peptide stimulation in vitro the generation of anti
      gp100 and tumor-specific T cell lines was achieved in one out of the six patients
      analyzed. Taken together these data indicate that an in vivo priming leading to a
      systemic immunity against gp100 in HLA-A3 melanoma patients may occasionally
      occur and that the immunogenicity of ALLAVGATK peptide in melanoma patients is
      comparable to that of other HLA-A2-restricted epitopes derived from gp100/Mel 17
      protein.

PMID- 9565354
TI  - Differential IgE recognition of recombinant Aspergillus fumigatus allergens by
      cystic fibrosis patients with allergic bronchopulmonary aspergillosis or
      Aspergillus allergy.
AB  - Allergic bronchopulmonary aspergillosis (ABPA), an intense inflammatory reaction
      to Aspergillus in the lung, is recognized as a severe complication in patients
      with cystic fibrosis (CF). The diagnosis of ABPA in CF patients sensitized to
      Aspergillus fumigatus is complicated by interfering laboratory and clinical
      findings shared by the diseases. We have used cDNA encoding A. fumigatus
      allergens which were cloned from a cDNA library displayed on phage surface to
      produce recombinant proteins in Escherichia coli. Differential IgE responses to
      the allergens in A. fumigatus-sensitized CF patients with or without ABPA and CF
      controls without sensitization to A. fumigatus were demonstrated. A secreted
      ribotoxin (rAsp f 1) and a peroxisomal protein (rAsp f 3) were recognized by sera
      from A. fumigatus-sensitized CF-patients with or without ABPA. An intracellular
      manganese superoxide dismutase (rAsp f 6) and rAsp f 4, a protein with unknown
      function, were recognized exclusively by IgE from sera of CF patients with ABPA.
      Therefore, Asp f 4 and Asp f 6 represent specific markers for ABPA and allow a
      sensitive, fully specific diagnosis of the disease. The data suggest distinct IgE
      responses to colonization of the bronchial tree in CF patients with ABPA or A.
      fumigatus allergy and therefore a differential recognition of the pathogen in the
      two IgE-related inflammatory diseases.

PMID- 9565355
TI  - A composite DNA element in the promoter of the polymeric immunoglobulin receptor
      regulates its constitutive expression.
AB  - The polymeric immunoglobulin receptor (pIgR), which is constitutively expressed
      on the basolateral surface of secretory epithelial cells, mediates external
      translocation of polymeric IgA and pentameric IgM (collectively called pIg) to
      exocrine secretions. A high level of synthesis must be maintained because the
      receptor is continuously cleaved to release bound secretory component (SC) in
      secretory IgA and secretory IgM, as well as free SC from unoccupied receptor. We
      have isolated the promoter of the pIgR gene and identified a short activating
      region that is required for the expression of pIgR promoter-driven reporter
      genes. This region contained an E-box and an inverted repeat sequence (IRS). Gel
      electrophoresis mobility shift assays with nuclear extracts from different pIgR
      expressing epithelial cell lines demonstrated proteins that bind independently to
      both the E-box and the IRS sequence of the pIgR promoter. In addition, a DNA
      probe that contained both the E-box and the IRS gave rise to a larger complex
      that could not be competed by either element on its own. Binding was confirmed by
      DNase I footprinting of the E-box and IRS sequences with nuclear extracts, and by
      dimethyl sulfide footprinting in living HT-29 epithelial cells. Finally, a
      mutation in the pIgR promoter that inhibited protein binding to the E-box and the
      formation of the larger complex, abolished activated transcription from the
      reporter gene.

PMID- 9565356
TI  - Evidence for the persistence of monoclonal expansions of CD8+ T cells following
      primary simian immunodeficiency virus infection.
AB  - A longitudinal study of the CD8+ TCR variable (Vbeta) chain repertoire was
      performed in rhesus macaques experimentally infected with simian immunodeficiency
      virus (SIV) using both TCR Vbeta chain-specific monoclonal antibodies and TCR
      beta chain CDR3 length analysis. Expansions of subpopulations of CD8+ T cells
      were detected during the acute phase of SIV infection. In all monkeys studied,
      monoclonal expansions persisted for at least 18 months and increasingly dominated
      the repertoire of CD8+ T cells expressing the relevant Vbeta chain. This study
      shows that persistent CD8+ T cell expansions develop in response to a virus
      infection. This is important not only for our understanding of the T cell
      response to viruses but also for understanding the factors that determine the
      normal CD8+ TCR repertoire.

PMID- 9565357
TI  - IFN-gamma inhibits the production of latent transforming growth factor-beta1 by
      mouse inflammatory macrophages.
AB  - Transforming growth factor (TGF)-beta is a multifunctional cytokine, which in
      mammals exists in three isoforms (TGF-beta1, 2 and 3). It is synthesized by a
      variety of cells including macrophages, and exerts potent immunoregulatory
      effects such as the inhibition of Th1 development and the suppression or reversal
      of IFN-gamma-induced macrophage activation. In this study we analyzed the effect
      of IFN-gamma on the production of TGF-beta1 by thioglycolate-elicited mouse
      peritoneal macrophages under serum-free conditions. Untreated macrophages
      released TGF-beta1 in its latent form, which became detectable in a capture ELISA
      specific for active TGF-beta1 after acid activation of the culture supernatants.
      Treatment with IFN-gamma reduced the amount of latent TGF-beta1 in the culture
      supernatants in a dose-dependent fashion. The effect of IFN-gamma was confirmed
      by a newly developed Western blot system for the detection of mouse TGF-beta1
      protein. IFN-gamma only weakly (16-24 %) reduced the levels TGF-beta1 mRNA at
      early and late time points of stimulation, and no evidence was obtained that IFN
      gamma suppresses the secretion of latent TGF-beta1. Thus, inhibition of TGF-beta1
      production by IFN-gamma is most likely due to decreased synthesis and/or
      stability of the TGF-beta1 protein, and might be important for the generation of
      fully activated macrophages and a Th1 response.

PMID- 9565359
TI  - Cellular interactions in the thymus regulate the protein kinase C signaling
      pathway.
AB  - We provide evidence that thymocytes receive signals from the thymic
      microenvironment which regulate the protein kinase C (PKC) signaling pathway.
      Thus, phorbol 12-myristate 13-acetate (PMA) causes a PKC-dependent down
      regulation of CD4 expression and induces apoptosis in isolated thymocytes but has
      little effect on thymocytes maintained within intact thymic lobes or in
      reaggregate lobes containing purified thymocytes with either thymic or non-thymic
      stromal cells. Moreover, compact pellets of thymocytes alone are protected from
      the effects of PMA. This protection is maintained when the compacted thymocytes
      are rigorously depleted of MHC class II-expressing cells. We conclude that
      signals arising from thymocyte-thymocyte contact control the utilization of the
      PKC cascade. These observations have implications for thymocyte signaling in
      general as well as for the interpretation of studies carried out on thymocyte
      suspensions.

PMID- 9565358
TI  - Up-regulated expression of decay-accelerating factor (CD55) confers increased
      complement resistance to sprouting neural cells.
AB  - We studied gene expression in relation to induced neural differentiation in a
      human neural crest-derived cell line, Paju. Messenger RNA isolated before and
      after treatment with phorbol 12-myristate 13-acetate was analyzed by differential
      display reverse transcription PCR. A strongly up-regulated expression of decay
      accelerating factor (DAF, CD55) was found to parallel the induced neural
      sprouting while the expression of two other complement regulatory proteins
      (CD59/protectin, CD46/membrane cofactor protein) remained unaltered during neural
      differentiation. The increased membrane expression of DAF, which was also seen on
      neural processes and growth cones, conferred elevated resistance to complement
      mediated lysis. Our findings suggest that in sprouting neurons DAF expression is
      up-regulated to provide additional complement resistance to pathfinding
      axons/dendrites invading new environment. It is also suggested that membrane
      expression of DAF may constitute a marker of growing and regenerating neurons.

PMID- 9565360
TI  - Functional diversity and clonal frequencies of reactivity in the available
      antibody repertoire.
AB  - The present experiments address functional antibody diversity and clonal
      distribution in murine available repertoires. IgM-containing supernatants were
      prepared by unbiased, polyclonal stimulation of resting splenic B cells from
      C57BL/6 mice, to ensure similar numbers of responding clones/culture and
      equivalent growth and maturation of all clones. The repertoires of clones and
      clonal mixtures were quantitatively assayed by limiting dilution analysis (LDA)
      on immunoblots of sodium dodecylsulfate polyacrylamide gel electrophoresis of
      homologous liver extracts, allowing to determine specific clonal frequencies
      towards the many hundred blotted antigens. The clonal frequency of reactivity of
      B cells with the extract was shown to be a bi-modal distribution of specific
      frequencies between 1/220 and 1/100,000. Cross-correlation analysis of reactivity
      to different bands in individual supernatants revealed low levels of cross
      reactivity, suggesting that the blotted extract provides a very diverse set of
      antigens. Investigation of the affinity/concentration thresholds for detection of
      antigen-antibody interactions of our assay supports the notion that global
      repertoire analyses on immunoblots were highly discriminative and non-degenerate.
      Furthermore, reactivity patterns obtained with complex antibody mixtures
      correlated with the frequency of clonal reactivities as determined by LDA. The
      results demonstrate a large functional diversity of resting B lymphocytes,
      indicating a minimal repertoire size that is orders of magnitude higher than
      previous theoretical proposals suggested, and extensively heterogeneous in the
      size of clonal specificities.

PMID- 9565361
TI  - Analysis of TCR beta chains in Lewis rats with experimental allergic
      encephalomyelitis. II. Vbeta8.2+ T cells with limited CDR3 N region additions
      derive from the adult thymus.
AB  - Immunization of Lewis (LEW) rats with guinea pig myelin basic protein (MBP)
      induces a population of encephalitogenic CD4 T cells having specificity for the
      dominant immunogenic peptide of MBP, 68-86. The TCR beta chains of these disease
      causing T cells show three distinct features: they are almost exclusively
      Vbeta8.2, they use AspSer as the first two amino acid residues of the third
      complementarity-determining region (CDR3) and these junctional region sequences
      show few if any non-germline N-region nucleotide additions. This last feature
      raises the possibility that these autoimmune T cell precursors derive from TCR
      gene rearrangements occurring during early, perinatal ontogeny, a period when the
      enzyme terminal deoxynucleotidyl transferase (TdT), responsible for N region
      additions, is not expressed. An alternative possibility is that these features of
      the TCR of MBP 68-86-reactive T cells are dictated by considerations of antigen
      selection throughout ontogeny both in the thymus and in the periphery--ie., that
      such beta chains are conformationally the most appropriate for triggering by an
      epitope of 68-86 complexed to class II RT1.BI MHC molecules. We show here that
      active experimental allergic encephalomyelitis, while delayed in onset, occurs in
      heavily irradiated animals, but not in the absence of a thymus, a finding
      indicating that this autoimmune disease is caused by a T cell subpopulation
      derived from the post-irradiation adult thymus. These disease-causing T cells are
      heavily Vbeta8.2+, CDR3 AspSer+ and use few N region additions. We conclude that
      T cells with these TCR beta chain features can be generated in the adult thymus
      and most likely reflect requirements imposed by antigen selection.

PMID- 9565362
TI  - Multi-plasmid DNA vaccination avoids antigenic competition and enhances
      immunogenicity of a poorly immunogenic plasmid.
AB  - DNA immunization is a very promising approach to the formulation of multivalent
      vaccines. However, little information is currently available on the
      immunogenicity of multi-plasmid formulations. To address this issue, we immunized
      mice with a combination of four plasmids encoding malarial antigens and we
      compared antibody responses with those obtained with single-plasmid injections.
      We found that when four plasmids encoding Plasmodium falciparum circumsporozoite
      protein, thrombospondin-related anonymous protein, major merozoite surface
      protein (MSP)1 and Pfs25 are co-injected into mice, Ab responses against each
      antigen are elicited at levels at least as high as the level obtained with single
      plasmid injection. The quality of antibody production, as determined by isotype
      analysis, was similar when single- and multi-plasmid administrations were
      compared, indicating the priming of the same cytokine profile for CD4+ T helper
      cells. The sera from mice immunized with the four-plasmid formulation
      specifically recognized sporozoites, blood stage schizonts and gametes,
      indicating that DNA immunization induced antibody responses relevant to the
      native conformation. Finally and of particular interest, in the case of MSP1, the
      antibody response appears to be strongly potentiated by the presence of
      additional plasmids, indicating an adjuvant effect of DNA.

PMID- 9565363
TI  - Selective immunomodulation by the autoimmunity-inducing xenobiotics
      streptozotocin and HgCl2.
AB  - Exposure to certain drugs and environmental chemicals can provoke the onset of
      autoimmune disease in susceptible individuals by releasing (self) epitopes for
      which tolerance has not been established, while simultaneously providing the
      necessary adjuvant activity. The resulting response type is influenced by the
      genotype of exposed individuals and relates to susceptibility to the adverse
      immune effects of the chemicals. Here, we assessed the modulatory role of the
      chemical compounds themselves. A single injection of streptozotocin (STZ)
      increased the number of CD8+ cells, macrophages, apoptotic cells, and IFN-gamma
      producing T helper and T cytotoxic cells, whereas the number of CD4+ cells and B
      cells was reduced in the draining lymph node. Coinjection with the reporter
      antigen TNP-OVA resulted in primary and secondary production of TNP-specific
      antibodies that were predominantly of IgG2a and IgG2b isotype, whereas STZ did
      not enhance priming for delayed-type hypersensitivity (DTH) responses to TNP-OVA.
      Injection of HgCl2 on the other hand, reduced the number of IFN-gamma-producing
      cells, induced accumulation of B cells and CD4+ and CD8+ T cells, enhanced IgG1
      and IgE production to TNP-OVA, and primed for secondary IgG1 and IgE production
      as well as for DTH reactions. Together these results indicate that a single
      injection of STZ stimulates type-1 responses, whereas HgCl2 enhanced mixed type-1
      and -2 responses in BALB/c mice. These response types match the (auto)immune
      effects elicited to unknown (auto)antigens following multiple injections of these
      chemicals.

PMID- 9565364
TI  - Mutational analysis of the role of ADP-ribosylation activity and GM1-binding
      activity in the adjuvant properties of the Escherichia coli heat-labile
      enterotoxin towards intranasally administered keyhole limpet hemocyanin.
AB  - The Escherichia coli heat-labile enterotoxin (LT) is known for its potent mucosal
      immunoadjuvant activity towards co-administered antigens. LT is composed of one A
      subunit, which has ADP-ribosylation activity, and a homopentameric B subunit,
      which has high affinity for the toxin receptor, ganglioside GM1. In previous
      studies, we have investigated the role of the LTA and LTB subunits in the
      adjuvanticity of LT towards influenza virus hemagglutinin (HA), administered
      intranasally to mice. We now studied the adjuvant properties of LT and LT
      variants towards keyhole limpet hemocyanin (KLH), which, in contrast to HA, does
      not bind specifically to mucosal surfaces. It is demonstrated that LT mutants
      without ADP-ribosylation activity, as well as LTB, retain mucosal immunoadjuvant
      activity when administered intranasally to mice in conjunction with KLH. As with
      influenza HA, adjuvanticity of LTB required GM1-binding activity, whereas GM1
      binding was not essential for adjuvant activity of LT. Furthermore, we found that
      also recombinant LTA alone acts as a potent mucosal adjuvant, and that this
      adjuvanticity is independent of ADP-ribosylation activity. It is concluded that
      binding of the antigen to mucosal surfaces does not play an essential role in the
      immunostimulation by LT and LT variants, and that both recombinant LTA and LTB
      represent powerful nontoxic mucosal adjuvants.

PMID- 9565365
TI  - Hierarchy in the ability of T cell epitopes to induce peripheral tolerance to
      antigens from myelin.
AB  - Nasal administration of peptide antigens has been shown to induce T cell
      tolerance. We have investigated the potential for peptide therapy of the
      autoimmune response to myelin antigens in experimental autoimmune
      encephalomyelitis (EAE). Three major encephalitogenic epitopes were studied for
      their ability to induce nasal tolerance to myelin antigens. These included
      epitopes Ac1-9 and 89-101 of myelin basic protein (MBP) and 139-151 from
      proteolipid protein (PLP). Peptide Ac1-9 from MBP effectively suppressed
      responses to both MBP epitopes, following immunization with whole myelin (linked
      suppression). The N-terminal epitope failed, however, to modify the response to
      epitope 139-151 of PLP. The second MBP epitope (89-101) was poorly tolerogenic
      for the immune response to any naturally processed myelin epitope. By contrast,
      PLP[139-151] was able to induce bystander suppression of T cells responsive to
      both itself and the two epitopes from MBP. Furthermore, this epitope suppressed
      EAE induced with peptides derived from MBP and was capable of treating ongoing
      disease. The mechanism of bystander suppression, mediated by PLP[139-151], did
      not correlate with an overt switch from the T helper 1 to the T helper 2
      phenotype. These results demonstrate how a complex autoimmune disease may be
      controlled by treatment with a single peptide epitope and reveal a hierarchy in
      the suppressive properties of different myelin antigens.

PMID- 9565366
TI  - Natural truncation of RANTES abolishes signaling through the CC chemokine
      receptors CCR1 and CCR3, impairs its chemotactic potency and generates a CC
      chemokine inhibitor.
AB  - Selective leukocyte trafficking towards sites of inflammation is mediated by
      chemokines. RANTES is a CC chemokine that attracts lymphocytes, monocytes,
      dendritic cells, eosinophils, basophils and NK cells. A natural form of human
      RANTES lacking two N-terminal residues was isolated from stimulated sarcoma
      cells, fibroblasts, and leukocytes. RANTES(3-68) showed a more than tenfold
      reduction in chemotactic potency for monocytes and eosinophils. To elucidate the
      mechanism involved, receptor recognition studies were performed. In cells
      transfected with the CC chemokine receptor (CCR) 5, the major co-receptor for
      macrophage-tropic HIV-1 strains, RANTES(3-68) mobilized calcium and desensitized
      RANTES(1-68)-induced calcium fluxes equally well as RANTES(1-68). However,
      RANTES(3-68) was ineffective on CCR1 and CCR3 transfectants. The reduced potency
      of natural RANTES(3-68) by selective loss of receptor-activating characteristics
      was confirmed with recombinant RANTES(3-68). In chemotaxis assays using monocytic
      cells, RANTES(3-68) inhibited RANTES(1-68), macrophage inflammatory protein
      1alpha (MIP-1alpha), MIP-1beta or monocyte chemotactic protein-3 (MCP-3), but not
      MCP-1- or MCP-2-induced chemotaxis. Thus, a minor post-translational modification
      has a remarkable impact on the biological activities of RANTES and a
      pathophysiologically induced change in the relative amounts of intact and
      truncated RANTES might affect the outcome of inflammation or HIV infection.

PMID- 9565367
TI  - Peptide length preferences for rat and mouse MHC class I molecules using random
      peptide libraries.
AB  - MHC class I molecules bind short peptides for presentation to CD8+ T cells. The
      determination of the three-dimensional structure of various MHC class I complexes
      has revealed that both ends of the peptide binding site are composed of polar
      residues conserved among all human and murine MHC class I sequences, which act to
      lock the ends of the peptide into the groove. In the rat, however, differences in
      these important residues occur, suggesting the possibility that certain rat MHC
      class I molecules may be able to bind and present longer peptides. Here we have
      studied the peptide length preferences of two rat MHC class Ia molecules
      expressed in the TAP2-deficient mouse cell line RMA-S: RT1-A1c, which carries
      unusual key residues at both ends of the groove, and RT1.Aa which carries the
      canonical residues. Temperature-dependent peptide stabilization assays were
      performed using synthetic random peptide libraries of different lengths (7-15
      amino acids) and successful stabilization was determined by FACS analysis.
      Results for two naturally expressed mouse MHC class I molecules revealed
      different length preferences (H2-Kb, 8-13-mer and H2-Db, 9-15-mer peptides). The
      rat MHC class Ia molecule, RT1-Aa, revealed a preference for 9-15-mer peptides,
      whereas RT1-A1c showed a more stringent preference for 9-12-mer peptides, thereby
      ruling out the hypothesis that unusual residues in rat MHC molecules allow
      binding of longer peptides.

PMID- 9565368
TI  - Specific engagement of the CD94/NKG2-A killer inhibitory receptor by the HLA-E
      class Ib molecule induces SHP-1 phosphatase recruitment to tyrosine
      phosphorylated NKG2-A: evidence for receptor function in heterologous
      transfectants.
AB  - It has been recently demonstrated that the CD94/NKG2-A killer inhibitory receptor
      (KIR) specifically recognizes the HLA-E class Ib molecule. Moreover, the apparent
      CD94-mediated specific recognition of different HLA class Ia allotypes,
      transfected into the HLA-defective cell line 721.221, indeed depends on their
      selective ability to concomitantly stabilize the surface expression of endogenous
      HLA-E molecules, which confer protection against CD94/NKG2-A+ effector cells. In
      the present study, we show that a selective engagement of the CD94/NKG2-A
      inhibitory receptor with a specific monoclonal antibody (mAb) (Z199) was
      sufficient to induce tyrosine phosphorylation of the NKG2-A subunit and SHP-1
      recruitment. These early biochemical events, commonly related to negative
      signaling pathways, were also detected upon the specific interaction of NK cells
      with an HLA-E+ 721.221 transfectant (.221-AEH), and were prevented by pre
      incubation of .221-AEH with an anti-HLA class I mAb. Furthermore, mAb cross
      linking of the CD94/NKG2-A receptor, segregated from other NK-associated
      molecules by transfection into a rat basophilic leukemia cell line (RBL-2H3),
      promoted tyrosine phosphorylation of NKG2-A and co-precipitation of SHP-1,
      together with an inhibition of secretory events triggered via Fc epsilonRI.
      Remarkably, interaction of CD94/NKG2-A+ RBL cells with the HLA-E+ .221-AEH
      transfectant specifically induced a detectable association of SHP-1 with NKG2-A,
      constituting a more formal evidence for the receptor-HLA class I interaction.

PMID- 9565369
TI  - Activation-induced NK cell death triggered by CD2 stimulation.
AB  - Both T cells and natural killer (NK) cells express CD2, the target of an
      alternative activation pathway that induces the proliferation of both cell types.
      The mitogenic response to CD2 ligation requires the co-expression of CD3:TCR in T
      cells and FcgammaRIII in NK cells, suggesting that these receptors are involved
      in transducing the response initiated by CD2. The ability of FcgammaRIII to
      trigger the activation-induced death of IL-2-primed NK cells led us to
      investigate the potential for CD2 to trigger activation-induced NK cell death.
      Our results reveal that the same anti-CD2 monoclonal antibodies (mAb) that
      activate freshly isolated NK cells induce apoptosis in IL-2-primed NK cells. CD2
      induced apoptosis results in chromatin condensation, DNA fragmentation and
      cleavage of caspase-3. Activation-induced NK cell death triggered by CD2 ligation
      is extremely rapid (DNA fragmentation is first observed at 90 min) and it is not
      inhibited by neutralizing antibodies reactive with TNF-alpha or Fas ligand.
      Whereas mAb reactive with distinct CD2 epitopes (i.e. T11.1, T11.2, and T11.3)
      are required for activation-induced T cell death, mAb reactive with a single CD2
      epitope are sufficient for activation-induced NK cell death. The ability of CD2,
      CD16, and CD94 to induce apoptosis in IL-2-primed lymphocytes suggests that
      cytokine priming changes the response to a signaling cascade that is common to
      each of these activation receptors.

PMID- 9565370
TI  - Enhanced MHC class II-restricted presentation of measles virus (MV) hemagglutinin
      in transgenic mice expressing human MV receptor CD46.
AB  - This study analyzes the role of the measles virus (MV) receptor, i.e. the human
      CD46 molecule, in the MHC class II-restricted presentation of MV hemagglutinin
      (H). We generated transgenic mice ubiquitously expressing CD46, with a similar
      level of transgene expression on the surface of antigen-presenting cells (APC),
      i.e. B cells, dendritic cells (DC) and macrophages. APC isolated from transgenic
      mice and nontransgenic controls were tested for their ability to present MV H to
      H-specific CD4+ I-Ed-restricted T cell hybridomas. All three populations of APC
      were capable of presenting MV to T cell hybridomas, DC being the most efficient.
      Expression of CD46 on B lymphocytes increased MHC class II-dependent presentation
      of MV H up to 100-fold, while CD46-transgenic DC stimulated H-specific T cell
      hybridomas up to 10-fold better than nontransgenic DC. Interestingly, expression
      of CD46 did not change the presentation efficiency of transgenic macrophages,
      indicating that CD46-dependent enhancement of antigen presentation depends on the
      nature of the APC. Furthermore, a single injection of UV-inactivated MV particles
      into CD46-transgenic mice, but not nontransgenic controls, induced generation of
      MV-specific T lymphocytes and production of anti-H antibodies, suggesting a role
      for CD46 in the efficient capture of MV in vivo. These results show for the first
      time that one ubiquitously expressed cell surface receptor, like CD46, could
      function in receptor-mediated antigen presentation both in vitro and in vivo and
      its performance depends on the type of APC which expresses it.

PMID- 9565371
TI  - Fine tuning of natural killer cell specificity and maintenance of self tolerance
      in MHC class I-deficient mice.
AB  - TAP1-/-, beta2-microglobulin (beta2m)-/- and TAP1/beta2m-/- mice all express low
      but quantitatively different levels of MHC class I molecules. Using these mice,
      we have addressed questions relating to the fine tuning of natural killer (NK)
      cell specificity and maintenance of self tolerance in the NK cell system. NK
      cells from B6 wild-type mice killed target cells from TAP1-/-, beta2m-/- and
      TAP1/beta2m-/- mice in vivo and rejected bone marrow grafts from the same mice in
      vivo at equivalent levels. NK cells from TAP1-/-, beta2m-/- mice did not kill
      target cells or reject bone marrow grafts from TAP1/beta2m-/- mice. NK cells in
      all MHC class I-deficient mice were tolerant to autologous MHC class I-deficient
      cells, as revealed by in vitro cytotoxicity assays using NK cell effectors
      activated with the interferon-inducing agent Tilorone, or by in vivo bone marrow
      graft experiments. However, the self-tolerant state of MHC class I-deficient NK
      cells was broken by in vitro stimulation with IL-2 for 4 days. Under these
      conditions, NK cells from the MHC class I-deficient mice killed autologous MHC
      class I-deficient cells while MHC class I-positive targets were spared. The C
      type lectin inhibitory receptor Ly49C has a specificity for H-2Kb and is
      expressed on a subset of NK1.1+ cells in B6 mice. Wild-type and all MHC class I
      deficient mice had similar numbers of Ly49C-positive NK1.1+ cells. However, Ly49C
      expression was markedly down-regulated on NK1.1+ cells from B6 mice, as compared
      to TAP1-/-, beta2m-/- and TAP1/beta2m-/- mice. In vitro stimulation of NK cells
      with IL-2 for 4 days did not significantly change this pattern. The present
      results are discussed in relation to the role of MHC class I molecules and Ly49
      receptors in shaping the NK cell repertoire and raise new questions about
      maintenance of self tolerance in the NK cell system.

PMID- 9565372
TI  - LFA-3 co-stimulates cytokine secretion by cytotoxic T lymphocytes by providing a
      TCR-independent activation signal.
AB  - T cell activation is known to depend not only on efficient antigen recognition
      and subsequent signaling through TCR, but also on interactions involving multiple
      adhesion and accessory molecules such as CD28/B7, LFA-1/ICAM-1 and LFA-3/CD2. The
      present study dissects the role of LFA-3/CD2 interactions in the activation of
      melanoma-specific CD8+ T cell clones. To this end we analyzed the influence of
      LFA-3 density on melanoma cells on lysis and cytokine production (TNF, IL-2, IFN
      gamma) by T cells following activation by various amounts of antigenic peptides.
      Our results indicate that increasing LFA-3 density on melanoma cells variably
      affects their lysis susceptibility, but systematically and considerably enhances
      cytokine production by melanoma-specific cytotoxic T lymphocyte (CTL) clones. At
      any stimulatory antigen density, LFA-3 increased the fraction of responding cells
      and/or cytokine amounts produced by individual cells, without affecting TCR down
      regulation. These results show that CD2 engagement increases cytokine gene
      activation essentially by providing to T cells a TCR-independent co-activation
      signal. From a practical point of view, our data demonstrate that the level of
      LFA-3 expressed on tumors critically affects cytokine production by specific CTL
      and thus the efficiency of specific immune reactions mediated by these cells.

PMID- 9565373
TI  - Mice with an inactivation of the inducible nitric oxide synthase gene are
      susceptible to experimental autoimmune encephalomyelitis.
AB  - Nitric oxide (NO) generated by the inducible nitric oxide synthase (iNOS) has
      been implicated in the pathogenesis of experimental autoimmune encephalomyelitis
      (EAE). In this study mice genetically deficient for iNOS are shown to be
      susceptible to EAE induced by immunization with myelin oligodendrocyte
      glycoprotein (MOG). In iNOS (-/-) mice the course of disease was earlier in onset
      and more aggressive compared to control animals. A disease-relevant compensatory
      up-regulation of neuronal (n)NOS and endothelial (e)NOS with increased production
      of NO in iNOS (-/-) mice is excluded by 1) the failure to detect increased nNOS
      and eNOS mRNA, 2) the absence of detection of nitrosylated tyrosine residues in
      EAE tissue indicating absence of NO-derived peroxynitrite, and 3) the lack of
      disease-preventing effects of NG-nitro-L-arginine methyl ester. In conclusion,
      these results do not support the hypothesis that NO is crucial for the
      development of EAE.

PMID- 9565374
TI  - Promiscuous liberation of MHC-class I-binding peptides from the C termini of
      membrane and soluble proteins in the secretory pathway.
AB  - TAP can efficiently transport peptides up to twice as long as those bound to MHC
      class I molecules, suggesting a role for endoplasmic reticulum (ER) proteases in
      the trimming of TAP-transported peptides. To better define ER processing of
      antigenic peptides, we examined the capacity of TAP-deficient cells to present
      determinants derived from ER-targeted proteins encoded by recombinant vaccinia
      viruses. TAP-deficient cells failed to present antigenic peptides from internal
      locations in secreted proteins to MHC class I-restricted T lymphocytes. The same
      peptides were liberated from the C termini of a secreted protein and the lumenal
      domains of two membrane proteins delivered to the ER via different routes. These
      findings suggest that proteases in the secretory compartment can liberate C
      terminal antigenic peptides from virtually any context. We propose that this
      activity often participates in the removal of N-terminal extensions from TAP
      transported peptides, thereby creating optimally sized products for MHC class I
      binding. We further demonstrate that ER trimming of C termini can occur if we
      express an appropriate carboxypeptidase in the secretory pathway. The absence of
      such trimming under normal circumstances suggests that carboxypeptidase activity
      is generally deficient in the ER, consistent with the concordance between the
      specificity of TAP and MHC class I molecules for the same types of C-terminal
      residues.

PMID- 9565375
TI  - Differential immunosuppressive activity of monoclonal CD2 antibodies on allograft
      rejection versus specific antibody production.
AB  - CD2 is a co-stimulatory receptor involved in T cell activation. Here we report on
      immunosuppressive effects of three mouse CD2 monoclonal antibodies (OX34, OX54,
      OX55) directed against non-overlapping epitopes of the rat CD2 receptor on
      various modes of T cell activation in vitro and in vivo. Although non-ligand
      blocking OX54 and OX55, in concert, activated T cells through CD2 in vitro, they
      individually suppressed the mixed lymphocyte reaction (MLR) and significantly
      prolonged allograft survival after rat heart transplantation in vivo. Phenotype
      analysis revealed that OX55 significantly down-modulated CD2 in vivo, whereas
      OX54 depleted T cells. Graft rejection coincided with re-expression of CD2 and
      clearance of OX55 from serum, whereas T cell depletion by OX54 outlasted the
      period of graft survival. The most suppressive antibody, OX34, down-modulated CD2
      and inhibited T cell activation through the TCR or CD2 and the MLR and prolonged
      median allograft survival time from 7 days in controls to 45 days in the absence
      of any additional treatment. Graft survival was clearly dose dependent and
      correlated with the duration of CD2 down-modulation and the presence of
      circulating CD2 antibody in serum. Importantly, the specific antibody production
      to a T cell-dependent antigen as demonstrated by immunization with keyhole limpet
      hemocyanin in vivo remained unaffected after treatment with OX34. These results
      demonstrate the pivotal role of CD2 signaling in mediating allogeneic immune
      reactions after vascularized organ transplantation while allowing specific
      humoral immune responses in vivo.

PMID- 9565376
TI  - In vivo and in vitro assessment of B-B cell interactions: inhibition of
      proliferation and antibody production of the CRIA B cells mediated by the surface
      immunoglobulins of anti-CRIA B cells.
AB  - In this work we have assessed the effect of cell surface anti-immunoglobulin (Ig)
      of anti-idiotypic B cells on their idiotypic counterparts in vivo and in vitro,
      as a surrogate for soluble anti-surface Ig, using the well-characterized anti
      arsonate system. The response of A/J mice against the hapten arsonate coupled to
      keyhole limpet hemocyanin (ARS-KLH) is dominated by a closely related family of
      antibodies sharing the same determinant, named the CRIA idiotype. We show herein
      that a massive induction of anti-CRIA B cells, subsequent to immunization with
      the mAb 3665 (CRIA+, arsonate binding) coupled to KLH, mediated a strong and long
      lasting inhibition of this dominant oligoclonal response to arsonate. The titer
      of anti-arsonate antibodies remained, however, unchanged. Adoptive transfers to x
      irradiated syngeneic mice showed that anti-CRIA-producing B cells have a direct
      effect on induction of inhibition. This was supported by the in vitro data where
      irradiated anti-CRIA B cells could induce inhibition of both antibody production
      and mitogenesis of their counterparts, CRIA B cells. This inhibitory effect could
      be decreased when the surface anti-surface Ig were hidden by the 3665 Fab
      fragments but not by anti-MHC class II antibodies. These interactions between
      CRIA and anti-CRIA B cells were solely Igh restricted and the inhibition was
      likely initiated by hyperaggregation of surface Ig. The presence of ARS-KLH
      primed T cells in vitro could prevent the growth inhibition but not the
      suppression of antibody production. A similar profile was noticed in vitro for
      soluble polyclonal rabbit anti-CRIA Ab. All together, our data suggest that a
      negative signaling in B cells may be initiated by surface Ig of their idiotypic
      partners subsequent to a strong cross-linking of their surface Ig receptors.

PMID- 9565377
TI  - Evidence of stage-specific element for germ-line transcription of the TCR alpha
      gene located upstream of J alpha49 locus.
AB  - T cell receptor (TCR) genes are rearranged and expressed in an ordered manner
      during T cell development. The basic mechanism regulating this stepwise DNA
      alteration is poorly understood. To address this issue, we explored the presence
      of a stage-specific element for germ-line transcription of the TCR alpha gene
      which is closely associated with gene rearrangement. First, germ-line
      transcription of the TCR alpha gene including the first segment of the J alpha
      locus, J alpha49, was delayed compared to that of the TCR beta gene in both
      normal and TCR-transgenic (Tg) mice. Furthermore, expression of this transcript
      could be induced by CD3epsilon-mediated signals in recombination-activating gene
      (RAG)-2-deficient mice. In TCR-Tg mice, the endogenous J alpha49 germ-line
      transcript could not yet be observed at the CD25+ double-negative (DN) stage when
      the TCR alpha transgene was expressed. Of immature T cell hybridomas derived from
      either scid thymocytes (CD25+ DN) or immature CD8-single positive (ISP)
      thymocytes, only the latter hybridoma expressed the J alpha49 germ-line
      transcript. These data indicate that the J alpha49 germ-line transcription occurs
      only at a specific developmental stage. Second, to determine which elements may
      be regulating stage specificity, we performed transient transfection analysis
      with a reporter gene and demonstrated that the upstream region of the J alpha49
      locus possesses promoter activity in correlation with germ-line transcription in
      ISP-derived but not in SCID-derived hybridomas. These results indicate that the
      expression of TCR alpha germ-line transcripts is regulated in a stage-specific
      manner by a cis-element located within the J alpha locus.

PMID- 9565378
TI  - Lymphadenopathy, elevated serum IgE levels, autoimmunity, and mast cell
      accumulation in flaky skin mutant mice.
AB  - The autosomal recessive mutation "flaky skin" (fsn) causes pleiotropic
      abnormalities in the immune and hematopoietic systems accompanied by pathologic
      changes in the skin. Homozygotes (fsn/fsn) showed increased size and histological
      alterations in the spleen and lymph nodes. Abnormalities in lymphoid architecture
      of the spleen in fsn/fsn mice were accompanied by marked increases in total
      numbers of B cells, macrophages, and immature erythroid cells. Splenic B cells
      displayed elevated MHC class II expression. Serum IgE levels were greater than
      100 microg/ml by 10 weeks of age, representing > 7000-fold increase compared with
      normal littermates. This increased IgE level was associated with elevated IL-4
      production by spleen cells and with increased amounts of serum IL-4. Serum IgM,
      IgG1, and IgG2b levels were also increased in fsn/fsn mice while IgG3 was
      decreased. Autoimmunity in fsn/fsn mice was evidenced by glomerulonephritis
      accompanied by immune complex deposition in the kidneys, increased serum blood
      urea nitrogen levels, and the presence of circulating anti-double-stranded DNA
      autoantibodies. Pathological changes in the skin of fsn/fsn mice were
      characterized by epidermal hyperplasia and mixed dermal inflammation. Increased
      numbers of mast cells were also observed in the dermis of the truncal skin as
      well as in the epithelial stomach. These marked immunological abnormalities
      suggest that the fsn locus encodes a major immunoregulatory molecule important in
      multiple immune and hematopoietic functions.

PMID- 9565379
TI  - Analysis of cytokine production by inflammatory mouse macrophages at the single
      cell level: selective impairment of IL-12 induction in Leishmania-infected cells.
AB  - Intracellular staining for cytokines and parasites, combined with two-color flow
      cytometric analyses, were used to examine the frequencies of IL-12-, TNF-alpha-
      and IL-6-producing macrophages in response to Leishmania major infection and/or
      activation with IFN-gamma/lipopolysaccharide (LPS). Inflammatory macrophages were
      obtained from nonimmune granulomas, initiated by the injection of polyacrylamide
      microbeads (Bio-gel P-100) into subcutaneous pouches of different mouse strains.
      Infection of inflammatory macrophages in vitro using metacyclic promastigotes
      produced identical effects on cytokine responses regardless of whether cells from
      genetically resistant or susceptible mouse strains were used: IL-12 was not
      produced in response to infection itself, virtually every infected cell lost its
      ability to produce IL-12 in response to IFN-gamma/LPS, and the IL-6 response was
      partially inhibited, while the TNF-alpha response of infected cells was
      unimpaired. Low-multiplicity infection of inflammatory macrophages in vivo using
      either metacyclic promastigotes or tissue amastigotes also resulted in the
      complete and selective inhibition of IL-12 responses in infected cells. These
      data establish the physiologic relevance of prior observations regarding the
      selective impairment of IL-12 induction pathways in infected macrophages, and
      suggest a mechanisms for the delayed onset of cell-mediated control mechanisms
      that is typical of even self-limiting forms of leishmanial disease.

PMID- 9565380
TI  - A recombinant virus-like particle system derived from parvovirus as an efficient
      antigen carrier to elicit a polarized Th1 immune response without adjuvant.
AB  - Hybrid virus-like particles (VLP) were prepared by self-assembly of the modified
      porcine parvovirus (PPV) VP2 capsid protein carrying a CD8+ or CD4+ T cell
      epitope. Immunization of mice with a single dose of these hybrid pseudo
      particles, without adjuvant, induced strong cytotoxic T lymphocyte and T helper
      (Th) responses against the reporter epitope. The Th response was characterized by
      a Th1 phenotype. We also analyzed in vitro the uptake mechanism of these
      parvovirus-like particles and the processing requirements associated with
      presentation by MHC molecules. Although previously shown to be presented by MHC
      class I molecules, these particles also enter very efficiently the MHC class II
      endocytic pathway, and behave as conventional exogenous antigens. Indeed, the
      processing of chimeric PPV:VLP was performed in endosomal/lysosomal acidic
      vesicles and the presentation of the foreign epitope carried by these particles
      was sensitive to brefeldin A and cycloheximide, showing that the foreign peptide
      was loaded on nascent MHC class II molecules. These results give some indication
      of how PPV:VLP can be presented by MHC class I and class II molecules, and
      underscore the wide potency of such VLP system to deliver foreign antigens for
      vaccine design.

PMID- 9565381
TI  - Type 1 and type 2 cytokine-producing mouse CD4+ and CD8+ T cells in acute
      Schistosoma mansoni infection.
AB  - CD4+ and CD8+ T cells can be divided based on the cytokines that they secrete
      into type 1 (Th1, Tc1) and type 2 (Th2, Tc2) subsets. Schistosoma mansoni
      infection in mice is characterized by a type 2-dominated response. We have used
      intracellular cytokine staining to demonstrate dramatic changes in the relative
      numbers of Tc1 and Th2 cells in the spleens of mice during acute schistosome
      infection. In infected mice prior to egg laying a generalized type 1 response
      dominated, and was associated with an expansion in the frequency of Tc1 and Th1
      cells. By week 7 after infection the cytokine response was of type 2, with an
      increase in the numbers of Th2 cells and a dramatic reduction in the frequency of
      Tc1 cells. Following the onset of egg laying there was apoptosis of cells in the
      spleens of mice, with CD4+ and in particular CD8+ T cells undergoing apoptosis.
      The loss of CD8+ T cells may in part be attributable to the development of a type
      2 environment, following egg laying, with type 2 responses mediating the
      apoptosis of Tc1 cells. Schistosome regulation of Tc1 during egg laying may be
      required to prevent type 1 inflammatory responses from exacerbating egg-induced
      pathology.

PMID- 9565382
TI  - The crucial role of IL-10 in the suppression of the immunological response in
      mice exposed to staphylococcal enterotoxin B.
AB  - Staphylococcal enterotoxin B (SEB), a bacterial superantigen, activates the
      immune system resulting in a burst of pro- and anti-inflammatory cytokines. A
      central anti-inflammatory mediator in this process is IL-10. Using IL-10
      deficient C57BL/6 (IL-10 KO) mice, we studied the role of endogenous IL-10 in the
      regulation of the immune response to SEB. SEB (100 microg) induced the release of
      IL-10 in control C57BL/6 [IL-10 wild type (WT)] mice, but not in their IL-10 KO
      counterparts. SEB-evoked plasma levels of TNF-alpha, IL-1beta, IL-2, IL-6, IL-12
      and IFN-gamma were significantly higher in the IL-10 KO mice than in the WT
      animals. The release of macrophage inflammatory proteins-1alpha and -2 was also
      enhanced in the IL-10 KO mice. Further, upon SEB challenge, mice deficient in IL
      10 produced higher levels of nitric oxide than the WT animals. IL-10 deficiency
      resulted in a marked enhancement of the SEB-induced apoptosis of thymocytes.
      Finally, IL-10 KO mice were more susceptible to SEB-induced lethal shock than
      their WT controls. These results show that IL-10 plays an important
      immunoregulatory role in the response to a superantigenic stimulus, by dampening
      of the shock-inducing inflammatory response and early activation-induced cell
      death elicited by SEB.

PMID- 9565383
TI  - IL-12 prevents neonatal induction of transplantation tolerance in mice.
AB  - We investigated the effect of IL-12 on the induction of transplantation tolerance
      by neonatal injection of allogenic cells. We first observed that injection of
      newborn BALB/c mice with IL-12 and (A/J x BALB/c)F1 spleen cells prevented the
      Th2 alloimmune response induced by neonatal inoculation of F1 cells alone and
      allowed the differentiation of T cells secreting high amounts of IL-2 and IFN
      gamma in mixed lymphocyte cultures with donor-type stimulators. Furthermore, IL
      12 administration resulted in the emergence of anti-donor cytotoxic T lymphocyte
      responses although at lower levels than in control uninjected mice. In parallel,
      we found that mice injected at birth with IL-12 and F1 cells did not develop
      chimerism and were able to reject a donor-type skin graft as efficiently as
      control mice. We conclude that IL-12 inhibits the Th2 polarization of the newborn
      response to alloantigens and prevents thereby the establishment of
      transplantation tolerance.

PMID- 9565384
TI  - The relation between health status changes and patient satisfaction in older
      hospitalized medical patients.
AB  - OBJECTIVE: To examine the relation between two patient outcome measures that can
      be used to assess the quality of hospital care: changes in health status between
      admission and discharge, and patient satisfaction. DESIGN: Prospective cohort
      study. SETTING AND PATIENTS: Subjects were 445 older medical patients (aged > or
      =70 years) hospitalized on the medical service of a teaching hospital.
      MEASUREMENTS AND MAIN RESULTS: We interviewed patients at admission and discharge
      to obtain two measures of health status: global health and independence in five
      activities of daily living (ADLs). At discharge, we also administered a 5-item
      patient satisfaction questionnaire. We assessed the relation between changes in
      health status and patient satisfaction in two sets of analyses, that controlled
      for either admission or discharge health status. When controlling for admission
      health status, changes in health status between admission and discharge were
      positively associated with patient satisfaction (p values ranging from .01 to
      .08). However, when controlling for discharge health status, changes in health
      status were no longer associated with patient satisfaction. For example, among
      patients independent in ADLs at discharge, mean satisfaction scores were similar
      regardless of whether patients were dependent at admission (i.e., had improved)
      or independent at admission (i.e., remained stable) (79.6 vs 81.2, p = .46).
      Among patients dependent in ADLs at discharge, mean satisfaction scores were
      similar regardless of whether they were dependent at admission (i.e., remained
      stable) or independent at admission (i.e., had worsened) (74.0 vs 75.7, p = .63).
      These findings were similar using the measure of global health and in
      multivariate analyses. CONCLUSIONS: Patients with similar discharge health status
      have similar satisfaction regardless of whether that discharge health status
      represents stable health, improvement, or a decline in health status. The
      previously described positive association between patient satisfaction and health
      status more likely represents a tendency of healthier patients to report greater
      satisfaction with health care, rather than a tendency of patients who improve
      following an interaction with the health system to report greater satisfaction.
      This suggests that changes in health status and patient satisfaction are
      measuring different domains of hospital outcomes and quality. Comprehensive
      efforts to measure the outcomes and quality of hospital care will need to
      consider both patient satisfaction and changes in health status during
      hospitalization.

PMID- 9565385
TI  - Intervention to increase mammography utilization in a public hospital.
AB  - OBJECTIVE: To study the effects of three approaches to increasing utilization of
      screening mammography in a public hospital setting in Northwest Louisiana.
      DESIGN: Randomized intervention study. POPULATION: Four hundred forty-five women
      aged 40 years and over, predominantly low-income and with low literacy skills,
      who had not had a mammogram in the preceding year. INTERVENTION: All
      interventions were chosen to motivate women to get a mammogram. Group 1 received
      a personal recommendation from one of the investigators. Group 2 received the
      recommendation plus an easy-to-read National Cancer Institute (NCI) brochure.
      Group 3 received the recommendation, the brochure, and a 12-minute interactive
      educational and motivational program, including a soap-opera-style video,
      developed in collaboration with women from the target population. MEASUREMENTS
      AND MAIN RESULTS: Mammography utilization was determined at 6 months and 2 years
      after intervention. A significant increase (p = .05) in mammography utilization
      was observed after the intervention designed in collaboration with patients (29%)
      as compared with recommendation alone (21%) or recommendation with brochure (18%)
      at 6 months. However, at 2 years the difference favoring the custom-made
      intervention was no longer significant. CONCLUSIONS: At 6 months there was at
      least a 30% increase in the mammography utilization rate in the group receiving
      the intervention designed in collaboration with patients as compared with those
      receiving the recommendation alone or recommendation with brochure. Giving
      patients an easy-to-read NCI brochure and a personal recommendation was no more
      effective than giving them a recommendation alone, suggesting that simply
      providing women in a public hospital with a low-literacy-level, culturally
      appropriate brochure is not sufficient to increase screening mammography rates.
      In a multivariate analysis, the only significant predictor of mammography use at
      6 months was the custom-made intervention.

PMID- 9565386
TI  - Does delirium contribute to poor hospital outcomes? A three-site epidemiologic
      study.
AB  - OBJECTIVE: To determine the independent contribution of admission delirium to
      hospital outcomes including mortality, institutionalization, and functional
      decline. DESIGN: Three prospective cohort studies. SETTING: Three university
      affiliated teaching hospitals. PATIENTS: Consecutive samples of 727 patients,
      aged 65 years and older. MEASUREMENTS AND MAIN RESULTS: Delirium was present at
      admission in 88 (12%) of 727 patients. The main outcome measures at hospital
      discharge and 3-month follow-up were death, new nursing home placement, death or
      new nursing home placement, and functional decline. At hospital discharge, new
      nursing home placement occurred in 60 (9%) of 692 patients, and the adjusted odds
      ratio (OR) for delirium, controlling for baseline covariates of age, gender,
      dementia, APACHE II score, and functional measures, was 3.0, (95% confidence
      interval [CI] 1.4, 6.2). Death or new nursing home placement occurred in 95 (13%)
      of 727 patients (adjusted OR for delirium 2.1, 95% CI 1.1, 4.0). The findings
      were replicated across all sites. The associations between delirium and death
      alone (in 35 [5%] of 727 patients) and between delirium and length of stay were
      not statistically significant. At 3-month follow-up, new nursing home placement
      occurred in 77 (13%) of 600 patients (adjusted OR for delirium 3.0; 95% CI 1.5,
      6.0). Death or new nursing home placement occurred in 165 (25%) of 663 patients
      (adjusted OR for delirium 2.6; 95% CI 1.4, 4.5). The findings were replicated
      across all sites. For death alone (in 98 [14%] of 680 patients), the adjusted OR
      for delirium was 1.6 (95% CI 0.8, 3.2). Delirium was a significant predictor of
      functional decline at both hospital discharge (adjusted OR 3.0; 95% CI 1.6, 5.8)
      and follow-up (adjusted OR 2.7; 95% CI 1.4, 5.2). CONCLUSIONS: Delirium is an
      important independent prognostic determinant of hospital outcomes including new
      nursing home placement, death or new nursing home placement, and functional
      decline-even after controlling for age, gender, dementia, illness severity, and
      functional status. Thus, delirium should be considered as a prognostic variable
      in case-mix adjustment systems and in studies examining hospital outcomes in
      older persons.

PMID- 9565387
TI  - Correlates and prevalence of benzodiazepine use in community-dwelling elderly.
AB  - OBJECTIVE: To describe the prevalence of benzodiazepine use, sociodemographic and
      physical health factors associated with use, dosages taken, and directions for
      use among individuals aged 65 years and older. DESIGN: Cross-sectional analysis
      of baseline data from the community-based, prospective observational
      Cardiovascular Health Study. PATIENTS/PARTICIPANTS: Medicare eligibility lists
      from four U.S. communities were used to recruit a representative sample of 5,201
      community-dwelling elderly, of which 5,181 participants met all study criteria.
      MEASUREMENTS AND MAIN RESULTS: Among participants, 511 (9.9%) were taking at
      least one benzodiazepine, primarily anxiolytics (73%). Benzodiazepines were often
      prescribed to be taken pro re nata (PRN "as needed"), and 36.5% of prescriptions
      with instructions to be taken regularly were taken at a dose lower than
      prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2% in
      benzodiazepine users and 3.3% in nonusers. In a multivariate logistic model, the
      significant independent correlates of benzodiazepine use were being white (odds
      ratio [OR] 1.9; 95% confidence interval [CI] 1.0, 3.4), female (OR 1.7; CI 1.4,
      2.2), and living in Forsyth County, North Carolina, or Washington County,
      Maryland, compared with living in Sacramento County, California, or Allegheny
      County, Pennsylvania (OR 2.3; CI 1.4, 2.2); having coronary heart disease (OR
      1.6; CI 1.2, 2.1), health status reported as poor or fair (OR 1.8; CI 1.4, 2.3),
      self-reported diagnosis of nervous or emotional disorder (OR 6.7; CI 5.1, 8.7),
      and reporting use of an OTC sleep aid medication (OR 18.7; CI 14.1, 24.7).
      CONCLUSIONS: One in 10 participants reported taking a benzodiazepine, most
      frequently an anxiolytic, often at a lower dose than prescribed and usually PRN.
      The high prevalence of OTC sleep aid medication and benzodiazepine use may place
      the patient at increased risk of psychomotor impairment. Physicians should assess
      OTC sleep aid medication use when prescribing benzodiazepines.

PMID- 9565388
TI  - Screening for problem drinking: impact on physician behavior and patient drinking
      habits.
AB  - OBJECTIVE: To assess the effect of a screen for problem drinking on medical
      residents and their patients. DESIGN: Descriptive cohort study. SETTING: Veterans
      Affairs Medical Clinic. PATIENTS: Patients were screened 2 weeks before a
      scheduled visit (n = 714). Physicians were informed if their patients scored
      positive. MEASUREMENTS AND MAIN RESULTS: Physician discussion of alcohol use was
      documented through patient interview and chart review. Self-reported alcohol
      consumption was recorded. Of 236 current drinkers, 28% were positive for problem
      drinking by the Alcohol Use Disorders Identification Test (AUDIT). Of 58 positive
      patients contacted at 1 month, 78% recalled a discussion about alcohol use, 58%
      were advised to decrease drinking, and 9% were referred for treatment. In 57
      positive patient charts, alcohol use was noted in 33 (58%), and a recommendation
      in 14 (25%). Newly identified patients had fewer notations than patients with
      prior alcohol problems. Overall, 6-month alcohol consumption decreased in both
      AUDIT-positive and AUDIT-negative patients. The proportion of positive patients
      who consumed more than 16 drinks per week (problem drinking) decreased from 58%
      to 49%. Problem drinking at 6 months was independent of physician discussion or
      chart notation. CONCLUSIONS: Resident physicians discussed alcohol use in a
      majority of patients who screened positive for alcohol problems but less often
      offered specific advice or treatment. Furthermore, residents were less likely to
      note concerns about alcohol use in charts of patients newly identified. Finally,
      a screen for alcohol abuse may influence patient consumption.

PMID- 9565390
TI  - Targeting depression interviewing: an exercise in diagnostic reasoning.

PMID- 9565389
TI  - What influences career choices among graduates of a primary care training
      program?
AB  - OBJECTIVE: To identify factors that influence primary care residents to become
      generalists or specialists. DESIGN: Structured survey and interview. SETTING: A
      large university-based, internal medicine residency program in primary care.
      PARTICIPANTS: Of 92 residency graduates who completed training between 1979 and
      1993, 88 (96%) participated. MAIN RESULTS: Although 82% of the participating
      graduates reported themselves very committed to primary care at the beginning of
      residency, only 68% pursued generalist careers. Factors influencing career choice
      that were more important to generalists than specialists included breadth of
      knowledge used in primary care practice (p = .04), breadth of clinical problems
      in practice (p = .001), and opportunity for continuity of care (p = .01).
      Although salary was rated "not important," 50% of generalists and specialists
      advocated increased salaries for generalists as a way to increase interest in
      primary care. Other promoting factors included mentors, increased prestige for
      generalists, community-based training, lifestyle changes, and decreased
      paperwork. Seventy-three percent of participants felt it was easier to be a
      specialist than a generalist. CONCLUSIONS: A substantial minority of primary care
      residents pursue specialty careers. To produce more generalists, graduates
      recommend addressing income inequities, providing generalist role models,
      increasing community-based teaching, and increasing prestige for generalists.

PMID- 9565391
TI  - Entitling the student doctor: defining the student's role in patient care.

PMID- 9565392
TI  - Laughter and balance: a letter to a junior resident.

PMID- 9565393
TI  - Patients' desires and expectations for medical care in primary care clinics.
AB  - To explore whether patients' desires for and expectations of medical care differ
      between the United States and Canada, we surveyed 652 patients and 105 physicians
      at primary care sites in Michigan and Ontario. Patient desires were similar at
      both sites, but expectations were higher in Michigan. Michigan physicians gave
      higher estimates of patient desire than physicians in Ontario. Physicians at both
      sites, however, similarly underestimated patients' desires. These between-site
      differences in expectation may reflect differences both in general cultural
      factors and in patient exposure to different clinical policies within the medical
      systems.

PMID- 9565394
TI  - Prevalence of domestic violence in an inpatient female population.
AB  - Studies have evaluated the prevalence of domestic violence in populations of
      patients in emergency and primary care settings, but there are little data on
      patients admitted to hospitals. We undertook a study to evaluate the prevalence
      of domestic violence among female inpatients. Of 131 consecutive female patients
      between the ages of 18 and 60 admitted to a nontrauma urban teaching hospital
      asked to complete a self-administered survey about domestic violence, 101
      completed the questionnaire. Twenty-six percent of the respondents reported being
      in an abusive relationship at one time. Two patients felt that domestic violence
      contributed to their current reason for admission. No respondents were asked
      about domestic violence by health care providers. Domestic violence is an
      uncommon but important precipitant to nontrauma hospital admissions. Physicians
      should query all female inpatients about domestic assault.

PMID- 9565395
TI  - Patient satisfaction with health care: critical outcome or trivial pursuit?

PMID- 9565396
TI  - Medical student name tags.

PMID- 9565398
TI  - Editorial: perspectives in general physiology 

PMID- 9565397
TI  - Disclosing medical mistakes.

PMID- 9565399
TI  - Molecular identity of the outwardly rectifying, swelling-activated anion channel:
      time to reevaluate pICln.

PMID- 9565400
TI  - The list of potential volume-sensitive chloride currents continues to swell (and
      shrink).

PMID- 9565401
TI  - Fast inactivation in Shaker K+ channels. Properties of ionic and gating currents.
AB  - Fast inactivating Shaker H4 potassium channels and nonconducting pore mutant
      Shaker H4 W434F channels have been used to correlate the installation and
      recovery of the fast inactivation of ionic current with changes in the kinetics
      of gating current known as "charge immobilization" (Armstrong, C.M., and F.
      Bezanilla. 1977. J. Gen. Physiol. 70:567-590.). Shaker H4 W434F gating currents
      are very similar to those of the conducting clone recorded in potassium-free
      solutions. This mutant channel allows the recording of the total gating charge
      return, even when returning from potentials that would largely inactivate
      conducting channels. As the depolarizing potential increased, the OFF gating
      currents decay phase at -90 mV return potential changed from a single fast
      component to at least two components, the slower requiring approximately 200 ms
      for a full charge return. The charge immobilization onset and the ionic current
      decay have an identical time course. The recoveries of gating current (Shaker H4
      W434F) and ionic current (Shaker H4) in 2 mM external potassium have at least two
      components. Both recoveries are similar at -120 and -90 mV. In contrast, at
      higher potentials (-70 and -50 mV), the gating charge recovers significantly more
      slowly than the ionic current. A model with a single inactivated state cannot
      account for all our data, which strongly support the existence of "parallel"
      inactivated states. In this model, a fraction of the charge can be recovered upon
      repolarization while the channel pore is occupied by the NH2-terminus region.

PMID- 9565402
TI  - Glutamine substitution at alanine1649 in the S4-S5 cytoplasmic loop of domain 4
      removes the voltage sensitivity of fast inactivation in the human heart sodium
      channel.
AB  - Normal activation-inactivation coupling in sodium channels insures that
      inactivation is slow at small but rapid at large depolarizations. M1651Q/M1652Q
      substitutions in the cytoplasmic loop connecting the fourth and fifth
      transmembrane segments of Domain 4 (S4-S5/D4) of the human heart sodium channel
      subtype 1 (hH1) affect the kinetics and voltage dependence of inactivation (Tang,
      L., R.G. Kallen, and R. Horn. 1996. J. Gen. Physiol. 108:89-104.). We now show
      that glutamine substitutions NH2-terminal to the methionines (L1646, L1647,
      F1648, A1649, L1650) also influence the kinetics and voltage dependence of
      inactivation compared with the wild-type channel. In contrast, mutations at the
      COOH-terminal end of the S4-S5/D4 segment (L1654, P1655, A1656) are without
      significant effect. Strikingly, the A1649Q mutation renders the current decay
      time constants virtually voltage independent and decreases the voltage
      dependences of steady state inactivation and the time constants for the recovery
      from inactivation. Single-channel measurements show that at negative voltages
      latency times to first opening are shorter and less voltage dependent in A1649Q
      than in wild-type channels; peak open probabilities are significantly smaller and
      the mean open times are shorter. This indicates that the rate constants for
      inactivation and, probably, activation are increased at negative voltages by the
      A1649Q mutation reminiscent of Y1494Q/ Y1495Q mutations in the cytoplasmic loop
      between the third and fourth domains (O'Leary, M.E., L.Q. Chen, R.G. Kallen, and
      R. Horn. 1995. J. Gen. Physiol. 106:641-658.). Other substitutions, A1649S and
      A1649V, decrease but fail to eliminate the voltage dependence of time constants
      for inactivation, suggesting that the decreased hydrophobicity of glutamine at
      either residues A1649 or Y1494Y1495 may disrupt a linkage between S4-S5/D4 and
      the interdomain 3-4 loop interfering with normal activation-inactivation
      coupling.

PMID- 9565403
TI  - Permeation and block of the skeletal muscle chloride channel, ClC-1, by foreign
      anions.
AB  - A distinctive feature of the voltage-dependent chloride channels ClC-0 (the
      Torpedo electroplaque chloride channel) and ClC-1 (the major skeletal muscle
      chloride channel) is that chloride acts as a ligand to its own channel,
      regulating channel opening and so controlling the permeation of its own species.
      We have now studied the permeation of a number of foreign anions through ClC-1
      using voltage-clamp techniques on Xenopus oocytes and Sf9 cells expressing human
      (hClC-1) or rat (rClC-1) isoforms, respectively. From their effect on channel
      gating, the anions presented in this paper can be divided into three groups:
      impermeant or poorly permeant anions that can not replace Cl- as a channel opener
      and do not block the channel appreciably (glutamate, gluconate, HCO3-, BrO3-);
      impermeant anions that can open the channel and show significant block
      (methanesulfonate, cyclamate); and permeant anions that replace Cl- at the
      regulatory binding site but impair Cl- passage through the channel pore (Br-, NO3
      , ClO3-, I-, ClO4-, SCN-). The permeability sequence for rClC-1, SCN-
      approximately ClO4- > Cl- > Br- > NO3- approximately ClO3- > I- >> BrO3- > HCO3-
      >> methanesulfonate approximately cyclamate approximately glutamate, was
      different from the sequence determined for blocking potency and ability to shift
      the Popen curve, SCN- approximately ClO4- > I- > NO3- approximately ClO3-
      approximately methanesulfonate > Br- > cyclamate > BrO3- > HCO3- > glutamate,
      implying that the regulatory binding site that opens the channel is different
      from the selectivity center and situated closer to the external side. Channel
      block by foreign anions is voltage dependent and can be entirely accounted for by
      reduction in single channel conductance. Minimum pore diameter was estimated to
      be approximately 4.5 A. Anomalous mole-fraction effects found for permeability
      ratios and conductance in mixtures of Cl- and SCN- or ClO4- suggest a multi-ion
      pore. Hydrophobic interactions with the wall of the channel pore may explain
      discrepancies between the measured permeabilities of some anions and their size.

PMID- 9565404
TI  - Self-inhibition in amiloride-sensitive sodium channels in taste receptor cells.
AB  - Electrophysiological recording techniques were used to study the Na+ dependence
      of currents through amiloride-sensitive sodium channels (ASSCs) in rat taste
      cells from the fungiform and vallate papillae. Perforated patch voltage clamp
      recordings were made from isolated fungiform and vallate taste receptor cells
      (TRCs) and Na+ transport was measured across lingual epithelia containing
      fungiform or vallate taste buds in a modified Ussing chamber. In isolated
      fungiform TRCs that contain Na+ currents sensitive to the diuretic amiloride, Na+
      ions inhibit their own influx through ASSCs, a process known as sodium self
      inhibition. Due to the interaction between self-inhibition and the driving force
      for Na+ entry, self-inhibition is most evident in whole-cell recordings at Na+
      concentrations from 50 to 75 mM. In amiloride-sensitive cells, the Na
      permeability is significantly higher in extracellular solutions containing 35 mM
      Na+ than in 70 or 140 mM Na+. Compared with the block by amiloride, the
      development of self-inhibition is slow, taking up to 15 s to become maximally
      inhibited. Approximately one third of fungiform TRCs and all vallate TRCs lack
      functional ASSCs. These amiloride-insensitive TRCs show no signs of self
      inhibition, tying this phenomenon to the presence of ASSCs. The sulfhydryl
      reagent, p-hydroxymercuribenzoate (p-HMB; 200 microM), reversibly removed self
      inhibition from amiloride-sensitive Na+ currents, apparently by modifying
      cysteine residues in the ASSC. Na+ currents in amiloride-insensitive TRCs were
      unaffected by p-HMB. In sodium transport studies in fungiform taste bud
      containing lingual epithelia, approximately 40% of the change in short-circuit
      current (Isc) after addition of 500 mM NaCl to the mucosal chamber is amiloride
      sensitive (0.5 mM). p-HMB significantly enhanced mucosal NaCl-induced changes in
      these epithelia at mucosal Na+ concentrations of 50 mM and above. In contrast,
      the vallate-containing epithelia, which are insensitive to amiloride, showed no
      enhancement of Isc during p-HMB treatment. These findings suggest that sodium
      self-inhibition is present in ASSCs in taste receptor cells where it may play a
      crucial role in performance of salt-sensitive pathways in taste tissue during
      sodium stimulation. This phenomenon may be important in the process of TRC
      adaptation, in the conservation of cellular resources during chronic sodium
      exposure, or in the gustatory response to water.

PMID- 9565405
TI  - Imperatoxin A induces subconductance states in Ca2+ release channels (ryanodine
      receptors) of cardiac and skeletal muscle.
AB  - Single-channel and [3H]ryanodine binding experiments were carried out to examine
      the effects of imperatoxin activator (IpTxa), a 33 amino acid peptide isolated
      from the venom of the African scorpion Pandinus imperator, on rabbit skeletal and
      canine cardiac muscle Ca2+ release channels (CRCs). Single channel currents from
      purified CRCs incorporated into planar lipid bilayers were recorded in 250 mM KCl
      media. Addition of IpTxa in nanomolar concentration to the cytosolic (cis) side,
      but not to the lumenal (trans) side, induced substates in both ryanodine receptor
      isoforms. The substates displayed a slightly rectifying current-voltage
      relationship. The chord conductance at -40 mV was approximately 43% of the full
      conductance, whereas it was approximately 28% at a holding potential of +40 mV.
      The substate formation by IpTxa was voltage and concentration dependent. Analysis
      of voltage and concentration dependence and kinetics of substate formation
      suggested that IpTxa reversibly binds to the CRC at a single site in the voltage
      drop across the channel. The rate constant for IpTxa binding to the skeletal
      muscle CRC increased e-fold per +53 mV and the rate constant of dissociation
      decreased e-fold per +25 mV applied holding potential. The effective valence of
      the reaction leading to the substate was approximately 1.5. The IpTxa binding
      site was calculated to be located at approximately 23% of the voltage drop from
      the cytosolic side. IpTxa induced substates in the ryanodine-modified skeletal
      CRC and increased or reduced [3H]ryanodine binding to sarcoplasmic reticulum
      vesicles depending on the level of channel activation. These results suggest that
      IpTxa induces subconductance states in skeletal and cardiac muscle Ca2+ release
      channels by binding to a single, cytosolically accessible site different from the
      ryanodine binding site.

PMID- 9565406
TI  - Functional differences in ionic regulation between alternatively spliced isoforms
      of the Na+-Ca2+ exchanger from Drosophila melanogaster.
AB  - Ion transport and regulation were studied in two, alternatively spliced isoforms
      of the Na+-Ca2+ exchanger from Drosophila melanogaster. These exchangers,
      designated CALX1.1 and CALX1.2, differ by five amino acids in a region where
      alternative splicing also occurs in the mammalian Na+-Ca2+ exchanger, NCX1. The
      CALX isoforms were expressed in Xenopus laevis oocytes and characterized
      electrophysiologically using the giant, excised patch clamp technique. Outward
      Na+-Ca2+ exchange currents, where pipette Ca2+o exchanges for bath Na+i, were
      examined in all cases. Although the isoforms exhibited similar transport
      properties with respect to their Na+i affinities and current-voltage
      relationships, significant differences were observed in their Na+i- and Ca2+i
      dependent regulatory properties. Both isoforms underwent Na+i-dependent
      inactivation, apparent as a time-dependent decrease in outward exchange current
      upon Na+i application. We observed a two- to threefold difference in recovery
      rates from this inactive state and the extent of Na+i-dependent inactivation was
      approximately twofold greater for CALX1.2 as compared with CALX1.1. Both isoforms
      showed regulation of Na+-Ca2+ exchange activity by Ca2+i, but their responses to
      regulatory Ca2+i differed markedly. For both isoforms, the application of
      cytoplasmic Ca2+i led to a decrease in outward exchange currents. This negative
      regulation by Ca2+i is unique to Na+-Ca2+ exchangers from Drosophila, and
      contrasts to the positive regulation produced by cytoplasmic Ca2+ for all other
      characterized Na+-Ca2+ exchangers. For CALX1.1, Ca2+i inhibited peak and steady
      state currents almost equally, with the extent of inhibition being approximately
      80%. In comparison, the effects of regulatory Ca2+i occurred with much higher
      affinity for CALX1.2, but the extent of these effects was greatly reduced (
      approximately 20-40% inhibition). For both exchangers, the effects of regulatory
      Ca2+i occurred by a direct mechanism and indirectly through effects on Na+i
      induced inactivation. Our results show that regulatory Ca2+i decreases Na+i
      induced inactivation of CALX1.2, whereas it stabilizes the Na+i-induced inactive
      state of CALX1.1. These effects of Ca2+i produce striking differences in
      regulation between CALX isoforms. Our findings indicate that alternative splicing
      may play a significant role in tailoring the regulatory profile of CALX isoforms
      and, possibly, other Na+-Ca2+ exchange proteins.

PMID- 9565407
TI  - Accuracy of a polymerase chain reaction-based assay for detection of pneumococcal
      bacteremia in children.
AB  - OBJECTIVE: To evaluate the utility of a polymerase chain reaction (PCR)-based
      assay for identifying pneumococcal DNA in the blood of pediatric patients with
      suspected bacteremia. METHODS: Children evaluated at the Children's Hospital of
      Pittsburgh who were having blood drawn for culture had an additional 2 to 3 mL of
      blood (from the same sampling) obtained and placed in a sodium citrate tube for
      PCR processing (study group). The control group for this study consisted of
      children having blood drawn for biochemical analysis who were afebrile, well
      appearing, and had no recent illnesses. Specimens were frozen at -70 degrees C
      and then batch-processed for PCR-based analyses with the JM201/202-204
      primer/probe set. Amplified products were detected after liquid hybridization
      format wherein a 32P end-labeled probe was annealed to the amplified DNA and
      visualized by autoradiographic analysis after gel retardation. RESULTS: Four
      hundred eighty study group patients and 103 controls had specimens tested by both
      PCR and blood culture. Twenty-six (5%) patients had a positive blood culture for
      a pathogenic organism (21 of which were Streptococcus pneumoniae). Twelve (57%)
      of the 21 patients with blood cultures positive for S pneumoniae also were
      positive by PCR. In addition, 206 study group patients and 16 controls with
      negative blood cultures had positive PCR results. A greater proportion of study
      group patients were PCR-positive/culture-negative than were controls (206/459 vs
      16/103). CONCLUSION: Although this assay currently lacks adequate sensitivity and
      specificity for clinical use, the high frequency of PCR-positive cases in
      patients with suspected bacteremia may indicate a greater role for S pneumoniae
      than had previously been appreciated. Further refinement of this assay as well as
      the development of a rapid PCR-based assay appears warranted.

PMID- 9565408
TI  - Intervention to improve physician documentation and knowledge of child sexual
      abuse: a randomized, controlled trial.
AB  - OBJECTIVE: To determine if written feedback improves the chart documentation and
      knowledge of physicians doing evaluations for child sexual abuse and to learn
      what other factors are associated with better documentation and knowledge.
      DESIGN: Randomized, controlled trial. SETTING: A statewide network of physicians
      performing child abuse evaluations. PARTICIPANTS: All physicians who performed
      evaluations for sexual abuse during 1991 to 1992. One hundred forty-seven
      physicians were randomized to control (n = 75) and intervention (n = 72) groups,
      122 (83%) remained at follow-up, and 87 of the 122 (71%) had done evaluations for
      child sexual abuse. INTERVENTIONS: Tailored written feedback based on chart
      reviews and relevant articles were sent to a randomly selected one-half of the
      physicians during a 3-month period. MAIN OUTCOME MEASURES: The quality of
      documentation and physician knowledge before and after the intervention. RESULTS:
      Documentation by chart review of up to five randomly chosen records per physician
      (preintervention, n = 552; postintervention, n = 259) by reviewers blinded to
      intervention status and physician knowledge was assessed by survey (78%
      completion). Change in documentation and knowledge for physicians in the
      intervention group was not statistically significant compared with the control
      group. The risk ratio for a mean overall history rating of excellent/good was
      0.89 (0.63, 1.25) and for a mean overall physical examination rating of
      excellent/good was 1.03 (0.73, 1.45). Both groups improved significantly during
      the time period. The largest improvements in the time period were in documenting
      the history of where abuse occurred, in the physical examination position,
      hymenal description, penile findings, and knowing that chlamydia infection should
      be assessed by culture. A structured medical record, female physicians, and
      credits in continuing medical education were associated with better
      documentation. CONCLUSIONS: Tailored feedback to the physician with directed
      educational materials did not seem to improve most aspects of documentation and
      knowledge of child sexual abuse, although notable improvement was seen during the
      time period studied. This study suggests that chart audits may not be the best
      use of resources for trying to improve physician behavior; credits in continuing
      medical education and use of structured records may be more likely to be
      beneficial.

PMID- 9565409
TI  - Pediatricians' awareness of and attitudes about four clinical practice
      guidelines.
AB  - BACKGROUND: The increasing complexity of medical care and a desire to increase
      quality and control costs have led to growing use of clinical practice guidelines
      (CPGs). It is unclear how helpful these guidelines are to the practitioners
      expected to use them. We surveyed pediatricians about their knowledge and
      impressions of four well-publicized CPGs: the American Academy of Pediatrics'
      "Practice Parameter for Hyperbilirubinemia in Newborns" (hyperbilirubinemia), "A
      Guideline for the Management of Febrile Infants" (fever), the Agency for Health
      Care Policy and Research's "Guideline for Otitis Media With Effusion" (otitis),
      and the US Preventive Services Task Force Guide to Clinical Preventive Services
      (preventive care). OBJECTIVES: 1) What percentage of practicing pediatricians are
      aware of these guidelines? 2) How helpful do they find them? 3) What are
      practitioners' perceived limitations of these guidelines? 4) Have these
      guidelines affected provider behavior? 5) Are there features of a provider's
      training or practice that are associated with changing practice as a result of
      guidelines? DESIGN: A national survey of 600 pediatricians selected at random
      from the American Medical Association master file. RESULTS: A total of 300 of 555
      eligible participants (54%) returned surveys. Of the respondents, 66% were aware
      of the hyperbilirubinemia guideline, 64% of the fever guideline, 50% of the
      otitis guideline, but only 16% knew of the preventive care guidelines. Mean
      helpfulness scores (1 to 10 scale, where 1 = "not at all helpful" and 10 =
      "extremely helpful") ranged from 3.67 to 6.67 for the different guidelines. In
      terms of limitations, 15% to 33% of respondents reported that CPGs were "too
      cookbook," 6% to 19% reported that they were "too time-consuming," and 4% to 16%
      reported that they were "too cumbersome." Additional reported limitations were
      believing that a guideline left no room for personal experience and judgment,
      concern of increased liability risk, and poor parental acceptance of CPG
      recommendations. The proportions reporting change in management as a result of a
      CPG were 28% for the hyperbilirubinemia guideline, 36% for the fever guideline,
      19% for the preventive care guidelines, and 28% for the otitis guideline. Mean
      helpfulness scores reported by nonuniversity-affiliated physicians were
      significantly higher than those reported by university-affiliated physicians. In
      a regression model of respondents aware of a particular guideline, more recent
      graduation from medical school and increased helpfulness scores were associated
      with guideline-related behavior change. CONCLUSION: In their present form, CPGs
      are not perceived as very helpful by most practitioners. More recent medical
      school graduates and nonuniversity-affiliated physicians are more likely to find
      them helpful and more likely to change their behavior because of them.

PMID- 9565411
TI  - Increasing breastfeeding rates to reduce infant illness at the community level.
AB  - OBJECTIVE: Although breastfeeding is associated with lower rates of a variety of
      infant illnesses, skeptics have suggested that much of the association is
      attributable to confounding, even after appropriate statistical adjustment. This
      article utilizes a novel design to investigate changes in infant illness at the
      community level after a successful breastfeeding promotion program. METHODS: In
      this population-based cohort study, the medical records of all infants born in
      one Navajo community the year before a breastfeeding promotion program (n = 977)
      and the year during the intervention (n = 858) were reviewed. Outcomes assessed
      include changes after the intervention in: proportion breastfeeding and/or
      breastfeeding exclusively; incidence of common infant illnesses in the first year
      of life; and feeding-group specific incidence of illness. RESULTS: The proportion
      of women breastfeeding exclusively for any period of time increased from 16.4% to
      54.6% after the intervention. The percent of children having pneumonia and
      gastroenteritis declined 32. 2% and 14.6%, respectively, after the intervention.
      Feeding-group specific rates of these illnesses were unchanged, indicating that
      the decline observed was attributable to the increased proportion of infants
      breastfeeding. In contrast, rates of croup and bronchiolitis increased after the
      intervention among those fed formula from birth, suggesting a viral epidemic
      which was limited to those never exclusively breastfed. Finally, sepsis declined
      in both formula-fed and breastfed infants after the intervention, suggesting that
      other factors affected this illness outcome after the intervention. CONCLUSIONS:
      Increasing the proportion of exclusively breastfed infants seems to be an
      effective means of reducing infant illness at the community level. The
      experimental design suggests that the increased incidence of illness among
      minimally breastfed infants is causally related to lack of breast milk, rather
      than being attributable to confounding.

PMID- 9565410
TI  - Impact of education for physicians on patient outcomes.
AB  - OBJECTIVES: This study was conducted to assess the impact of an interactive
      seminar based on self-regulation theory on 1) the treatment practices and
      communications and education behavior of physicians, 2) the health status and
      medical care utilization of their pediatric patients with asthma, and 3) the
      satisfaction with care of the subjects' parents. METHODS: A total of 74 general
      practice pediatricians were assigned to either a program or a control group in a
      randomized controlled study. Data were collected from physicians at baseline, and
      69 (93%) provided follow-up data 5 months after the program. Data were also
      collected from 637 of their patients at baseline, and in a 22-month window after
      the intervention, 472 (74%) of this number provided follow-up data. RESULTS:
      After the seminar, physicians in the program group were more likely than were
      control group physicians to address patients' fears about medicines, review
      written instructions, provide a sequence of educational messages, write down how
      to adjust the medicines at home when symptoms change, and report that they spent
      less time with their patients. Parents of the children treated by program
      physicians were significantly more likely than were control group parents to
      report that the physician had been reassuring, described as a goal that the child
      be fully active, and gave information to relieve specific worries. After a visit
      with the physician, these parents were also more likely to report that they knew
      how to make management decisions at home. After the intervention compared to
      controls, patients of physicians in the program group were more likely to have
      received a prescription for inhaled antiinflammatory medicine and to have been
      asked by the physician to demonstrate how to use a metered-dose inhaler. After
      the intervention, children seen by program physicians made significantly fewer
      nonemergency office visits and visits for follow-up of an episode of symptoms;
      however, there were no differences in emergency department visits and
      hospitalizations. Among children who were placed on inhaled corticosteroids
      during this study, however, children treated by physicians who had received
      education had significantly fewer symptoms and fewer follow-up office visits,
      nonemergency physician office visits, emergency department visits, and
      hospitalizations. CONCLUSIONS: The interactive seminar based on theories of self
      regulation led to patient-physician encounters that were of shorter duration, had
      significant impact on the prescribing and communications behavior of physicians,
      led to more favorable patient responses to physicians' actions, and led to
      reductions in health care utilization.

PMID- 9565412
TI  - Adverse asthma outcomes among children hospitalized with asthma in California.
AB  - OBJECTIVE: To use administrative data to determine whether adverse asthma
      outcomes for pediatric asthma hospitalizations are related to specific clinical
      and nonclinical patient characteristics. DESIGN: Cross-sectional study. SETTING:
      All pediatric (0 to 17 years of age) asthma-related hospital discharges, 1986 to
      1993, in California. PATIENTS: A total of 113 974 eligible patients with asthma
      related discharges. MAIN OUTCOME MEASURE: Adverse asthma outcomes (intubation,
      cardiopulmonary arrest, and death). RESULTS: Adverse asthma outcomes occurred in
      0.48% of subjects. The frequency of adverse asthma outcomes increased during the
      1990s compared with 1986. After controlling for differences in gender, age,
      specific comorbid conditions, year, race, and insurance type, adverse asthma
      outcomes were more likely to occur in the 5- to 11-year-old group (odds ratio
      [OR]: 1.39; 95% confidence interval [CI]: 1.13-1.69) and in the 12- to 17-year
      old group (OR: 4.48; CI: 3.20-6.21) compared with those children in the 0 to 4
      year-old age group. Asian Pacific-American children were more likely (OR: 1.59;
      CI: 1.24-2.59) than were white children to experience an adverse asthma outcome.
      Children who had a secondary diagnoses of pneumonia (OR: 1.54; CI: 1. 19-2.00)
      also were more likely to experience an adverse asthma outcome. The odds of an
      adverse outcome increased progressively after 1986, becoming significant after
      1989. Gender and insurance type were not associated with increased odds of
      experiencing an adverse asthma outcome. CONCLUSIONS: Adverse asthma outcomes
      among hospitalized children are increasing in the 1990s and are associated with
      specific clinical and nonclinical patient characteristics.

PMID- 9565413
TI  - Buccal cell DNA mutation analysis for diagnosis of cystic fibrosis in newborns
      and infants inaccessible to sweat chloride measurement.
AB  - OBJECTIVES: To assess the application of DNA-based cystic fibrosis transmembrane
      conductance regulator (CFTR) gene mutation analysis as a primary cystic fibrosis
      (CF) diagnostic test in preterm and term newborns and infants for whom the
      quantitative pilocarpine iontophoresis test (QPIT) cannot be used. DESIGN:
      Retrospective survey. SETTING: DNA Diagnostic Laboratory, Children's Hospital,
      Boston, Massachusetts. Buccal cell DNA samples were received from inpatients,
      outpatients, and three neonatal intensive care units. OUTCOME MEASURE: Detection
      of at least 1 of 12 CFTR mutations. PATIENTS: Between November 1, 1992, and April
      30, 1994, 28 newborns and infants under 12 months of age at risk for CF had CFTR
      DNA mutation analysis performed because a sweat chloride (SC) value could not be
      obtained. QPIT was either not performed (infant weight <2 kg, QPIT not available
      at site of hospitalization, or infant not accessible to QPIT laboratory) or was
      inconclusive (sweat volume <75 mg or indeterminate SC [>/=40, <60 mEq/L]). The
      postnatal age at time of testing ranged from 1 day to 11 months, and gestational
      age at birth from 25 to 40 weeks. RESULTS: Six (21%) of 28 infants with
      unobtainable or indeterminate QPIT had 1 or 2 CFTR mutations detected. Immediate
      CF diagnosis by direct detection of 2 CFTR mutations was made in 5 of these 6
      patients. Definitive CF diagnosis in the infant with 1 CFTR mutation was delayed
      until an elevation in SC could be documented. The patients with no CFTR mutations
      detected had a low likelihood of CF. CONCLUSIONS: For infants in whom CF is
      suspected but QPIT cannot be obtained, buccal cell DNA-based CFTR mutation
      analysis can be used as a rapid, noninvasive primary diagnostic test. This simple
      mode of DNA collection may aid in the diagnosis of other inherited disorders in
      newborns.

PMID- 9565414
TI  - Health and developmental outcomes at 18 months in very preterm infants with
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: To determine whether very preterm infants who are oxygen-dependent at
      28 days of life but not at 36 weeks' gestational age are at high risk of
      morbidities at 18 months. POPULATION: A total of 217 infants born in a tertiary
      care center at 24 to 28 weeks' gestation in 1987 to 1992, classified into three
      groups: neonatal comparison group, O2 <28 days of life (n = 76); bronchopulmonary
      dysplasia (BPD)-1, O2 >/=28 days but not at 36 weeks' gestational age (n = 48);
      and BPD-2, O2 >/=36 weeks (n = 93). OUTCOME MEASURES: Growth, persistent
      respiratory problems (asthma, tracheostomy, home oxygen therapy), surgery,
      hospitalizations, and neurodevelopmental impairments. RESULTS: Among the three
      groups, no differences were found in weight, height, head circumference, or total
      number of days of rehospitalizations for any causes, or in rate of
      rehospitalizations to the intensive care unit, persistent respiratory problems,
      cerebral palsy, or sensory impairment. Children with BPD-2 needed more hernia
      repairs compared with the other two groups (comparison group: 12% vs BPD-1: 10%
      vs BPD-2: 30%), had more days of readmissions for respiratory problems
      (comparison group: 2.0 vs BPD-1: 2.0 vs BPD-2 6.3 [BPD-1 vs BPD-2]), had a lower
      mean developmental quotient (comparison group: 97.4 +/- 15.0 vs BPD-1: 97.9 +/-
      11.6 vs BPD-2: 90.7 +/- 19.3). Intraparenchymal cerebral lesions, high family
      adversity, and prolonged ventilation were the most important factors influencing
      the developmental outcome. CONCLUSION: Children with BPD-1 are similar in all
      respect at 18 months to children in the comparison group. Children with BPD-2 are
      similar to the other groups at 18 months in growth, general health, and
      neurologic outcome but differ in having a higher number of days of
      rehospitalizations for respiratory causes, more hernia repairs, and more
      developmental delays.

PMID- 9565415
TI  - Serum cholesterol and triglyceride distribution in 7767 school-aged Greek
      children.
AB  - OBJECTIVE: To elucidate associations of age and sex with serum cholesterol and
      triglyceride levels and to provide for the first time percentile distribution
      data for pediatric lipids. PARTICIPANTS AND METHODS: A high sample of 7767 (3980
      boys, 3787 girls) fasting schoolchildren, 6 to 14 years of age, were studied in
      Athens, Greece. RESULTS: The mean cholesterol ranged from 157 to 174 mg/dL for
      boys and from 158 to 172 mg/dL for girls peaking at 9 years of age for both
      sexes. Triglyceride levels also tended to increase gradually and to peak at 11
      years of age for both sexes. The high-density lipoprotein cholesterol levels were
      highest at 9 years of age for both sexes and the low-density lipoprotein
      cholesterol levels also tended to peak at 9 years of age for boys and at 8 years
      of age for girls. Atherogenic indices ranged from 1.54 to 1.68 for boys and 1. 51
      to 1.85 for girls. CONCLUSION: According to these findings, it could be suggested
      that diet changes in the Greek population, especially in children and
      adolescents, living in big cities is significantly influencing their total
      cholesterol profiles throughout the last 10 years.

PMID- 9565416
TI  - Somatosensory evoked potentials in very preterm infants in relation to L
      thyroxine supplementation.
AB  - OBJECTIVE: To study the effect of L-thyroxine supplementation on neurologic
      maturation in very preterm infants with transient hypothyroxinemia. DESIGN:
      Randomized, double-blind, placebo-controlled, L-thyroxine supplementation trial.
      SETTING: Level III neonatal intensive care unit. SUBJECTS: A total of 200 infants
      <30 weeks' gestational age. INTERVENTION: Subjects were randomly assigned to
      receive L-thyroxine (8 microg/kg birth weight per day) or a placebo during the
      first 6 weeks of life. METHODS: Median nerve somatosensory evoked potentials were
      recorded, measuring cortical N1 peak latency at 2 weeks of age, at term, and at 6
      months (corrected) age. RESULTS: Cortical N1 peak latency was not decreased
      significantly in the L-thyroxine group compared with the placebo group throughout
      the study period. CONCLUSION: L-Thyroxine supplementation during the first 6
      weeks of life did not decrease cortical N1 peak latency in infants of <30 weeks'
      gestational age.

PMID- 9565417
TI  - Plasma 3-nitrotyrosine is elevated in premature infants who develop
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: Premature infants are susceptible to bronchopulmonary dysplasia (BPD),
      a chronic lung disease of infancy that appears to be caused in part by oxidative
      stress from hyperoxia. To investigate the possible role of nitric oxide-derived
      oxidants such as peroxynitrite in the etiology of BPD, we measured levels of
      plasma 3-nitrotyrosine, which is produced by the reaction of peroxynitrite with
      proteins. PATIENTS AND METHODS: Ten premature infants who developed BPD, defined
      as requiring supplemental oxygen beyond 36 weeks' postmenstrual age, were
      identified retrospectively from a group of subjects enrolled in a clinical trial
      of antenatal therapy. Serial plasma samples had been collected on these infants
      during the first month of life as part of the trial. Sixteen comparison premature
      infants were identified from the same population: 5 had no lung disease, 6 had
      respiratory distress syndrome that resolved, and 5 had residual lung disease at
      28 days of life that resolved by 36 weeks' postmenstrual age. Plasma 3
      nitrotyrosine levels were measured using a solid phase immunoradiochemical
      method. RESULTS: All 3-nitrotyrosine values in infants without BPD were <0.25
      ng/mg protein, and levels did not change with postnatal age. Plasma 3
      nitrotyrosine concentrations were significantly higher in infants with BPD,
      increasing approximately fourfold during the first month of life. For the 20
      infants who had blood samples available at 28 days of life, plasma 3
      nitrotyrosine levels correlated with the fraction of inspired oxygen that the
      infant was receiving (r = 0.7). CONCLUSION: Plasma 3-nitrotyrosine content is
      increased during the first month of life in infants who develop BPD. This
      suggests that peroxynitrite-mediated oxidant stress may contribute to the
      development of this disease in premature infants and that 3-nitrotyrosine may be
      useful as an early plasma indicator of infants at risk for developing BPD.

PMID- 9565418
TI  - Cystatin C--a new marker of glomerular filtration rate in children independent of
      age and height.
AB  - OBJECTIVES: Serum creatinine is the most common endogenous marker of renal
      function. The proportionality between creatinine production and muscle mass
      requires adjustment for height and body composition. The low molecular weight
      protein cystatin C is produced by all nucleated cells and eliminated by
      glomerular filtration. Therefore, cystatin C was studied as an alternative marker
      of glomerular filtration rate (GFR) in children. METHODS: Cystatin C and
      creatinine were measured in sera from inulin clearance (CIn) examinations
      performed in 184 children aged 0.24 to 17.96 years. CIn ranged from 7 to 209
      mL/min/1.73 m (median, 77). RESULTS: The reciprocal of cystatin C correlated
      better with CIn (r = 0.88) than the reciprocal of creatinine (r = 0.72). Stepwise
      regression analysis identified no covariates for the correlation between cystatin
      C and CIn, whereas height was a covariate for creatinine. Using an estimate of
      GFR from serum creatinine and height, correlation with CIn was similar to
      cystatin C, but female gender and dystrophy were associated with an
      overestimation of GFR. Diagnostic accuracy in the identification of reduced GFR
      measured as area under the receiver-operating characteristic plot was 0.970 +/-
      0.135 (mean +/- SE) for cystatin C and 0.894 +/- 0.131 for creatinine (NS). A
      cutoff cystatin C concentration of 1.39 mg/L had 90% sensitivity and 86%
      specificity for detecting abnormal GFR. CONCLUSION: Unlike creatinine, serum
      cystatin C reflects renal function in children independent of age, gender,
      height, and body composition.

PMID- 9565419
TI  - Venipuncture is more effective and less painful than heel lancing for blood tests
      in neonates.
AB  - OBJECTIVE: Heel lancing has hitherto been the method of choice for screening
      tests of inborn errors of metabolism in neonates. Eutectic mixture of local
      anesthetic has little, if any, analgesic effect when applied to the heel of pre-
      and full-term infants. Today there seems to be no practical method that
      effectively alleviates the pain caused by heel lancing. The aim of this study was
      to investigate whether other methods, such as venipuncture of the dorsal side of
      the hand, are less painful and more efficient than heel lancing in neonates.
      METHODS: One hundred twenty healthy, full-term infants who underwent testing for
      phenylketonuria (PKU) were included in the study. They were randomized into three
      groups: a venipuncture group (VP) (n = 50), a heel-lance group with a small
      lancet (SL) (n = 50), or a large lancet (LL) (n = 20). Pain reactions were
      assessed by the Neonatal Facial Coding System (NFCS). The latency and duration of
      the first cry as well as the total screaming time was analyzed. The efficacy of
      the method was assessed by the time taken to complete the PKU test and number of
      times the skin had to be punctured. RESULTS: Nociceptive response. The NFCS
      scores after the first skin puncture were: VP, 247; SL, 333; and LL, 460. The
      NFCS scores were significantly lower in the VP than in the groups subjected to
      heel lancing. During the first 60 seconds after skin puncture, 44% of the infants
      cried in the VP group, compared with 72% and 85% in the SL and LL groups,
      respectively. Efficacy. A successful PKU test with only one skin puncture was
      performed in 86% of the VP group, but in only 19% in the SL group and 40% in the
      LL group. The total time needed to obtain the PKU blood sample was 191 seconds
      (median) in the VP group, 419 seconds in the SL group, and 279 seconds in the LL
      group. CONCLUSION: Venipuncture is more effective and less painful than heel
      lancing for blood tests in neonates.

PMID- 9565420
TI  - Developmental changes in energy expenditure and physical activity in children:
      evidence for a decline in physical activity in girls before puberty.
AB  - OBJECTIVE: To examine individual changes in energy expenditure and physical
      activity during prepubertal growth in boys and girls. METHODS: Total energy
      expenditure (TEE), resting energy expenditure, physical activity-related energy
      expenditure, reported physical activity, and fat and fat-free mass were measured
      three times over 5 years in 11 boys (5.3 +/- 0.9 years at baseline) and 11 girls
      (5.5 +/- 0.9 years at baseline). RESULTS: Four-year increases in fat (
      approximately 6 kg) and fat-free mass ( approximately 10 kg) and resting energy
      expenditure ( approximately 200 kcal/day) were similar in boys and girls. In
      boys, TEE increased at each measurement year, whereas in girls, there was an
      initial increase from age 5.5 (1365 +/- 330 kcal/day) to age 6.5 (1815 +/- 392
      kcal/day); however, by age 9.5, TEE was reduced significantly (1608 +/- 284
      kcal/day) with no change in energy intake. The gender difference in TEE changes
      over time was explained by a 50% reduction in physical activity (kcal/day and
      hours/week) in girls between the ages of 6.5 and 9.5. CONCLUSIONS: These data
      suggest a gender dimorphism in the developmental changes in energy expenditure
      before adolescence, with a conservation of energy use in girls achieved through a
      marked reduction in physical activity.

PMID- 9565421
TI  - Management of acute gastroenteritis in children in Israel.
AB  - OBJECTIVE: Diarrheal diseases are a major cause of morbidity and mortality
      worldwide. Guidelines about the use of oral rehydration solutions (ORS) and
      dietary management of acute gastroenteritis (GE) were recently revised and
      published by the American Academy of Pediatrics (AAP). Study aims were to examine
      Israeli pediatricians' knowledge and implementation of the revised AAP
      guidelines, the effect of medical school (Israeli versus foreign medical
      graduates) on the physicians' practice, and the effect of the type of practice
      (community vs hospital-based) on the management of gastroenteritis. METHODS: A
      multiple-choice, written questionnaire was distributed at two pediatrics annual
      meetings. RESULTS: A total of 87 pediatricians completed the questionnaire. They
      were aware of 73% of the current AAP guidelines and followed 60% of the
      guidelines. Most pediatricians (83%) use ORS for treatment of dehydration in GE,
      but 60% of pediatricians believe that full-strength feeds are inappropriate in
      the presence of GE, and 67% of them do not recommend full-strength formulas. In
      addition, 37% of the pediatricians stop feeding temporarily in the presence of
      GE, in contrast to the 1996 AAP guidelines. There were no differences in
      knowledge and management practices among pediatricians graduating in Israel,
      Europe, or the United States, and no differences between pediatricians working in
      an ambulatory setting or in a hospital. CONCLUSIONS: Pediatricians in Israel,
      regardless of country of origin, medical school, or place of practice, are aware
      of the correct use of ORS but do not follow nutritional practices recommended
      recently by the AAP. These findings suggest that steps for implementing the
      guidelines are needed in Israel and most probably worldwide.

PMID- 9565422
TI  - The association between health risk behaviors and sexual orientation among a
      school-based sample of adolescents.
AB  - OBJECTIVE: This study is one of the first to examine the association between
      sexual orientation and health risk behaviors among a representative, school-based
      sample of adolescents. DESIGN: This study was conducted on an anonymous,
      representative sample of 4159 9th- to 12th-grade students in public high schools
      from Massachusetts' expanded Centers for Disease Control and Prevention 1995
      Youth Risk Behavior Survey. Sexual orientation was determined by the following
      question: "Which of the following best describes you?" A total of 104 students
      self-identified as gay, lesbian, or bisexual (GLB), representing 2.5% of the
      overall population. Of GLB youth, 66.7% were male and 70% were white (not
      Hispanic). Health risk and problem behaviors were analyzed comparing GLB youth
      and their peers. Those variables found to be significantly associated with GLB
      youth were then analyzed by multiple logistic regression models. RESULTS: GLB
      youth were more likely than their peers to have been victimized and threatened
      and to have been engaged in a variety of risk behaviors including suicidal
      ideation and attempts, multiple substance use, and sexual risk behaviors. Four
      separate logistic regression models were constructed. Model I, Onset of Behaviors
      Before Age 13, showed use of cocaine before age 13 years as strongly associated
      with GLB orientation (odds ratio [OR]: 6.10; 95% confidence interval [CI] = 2.45
      15.20). Early initiation of sexual intercourse (2.15; 10.6-4.38), marijuana use
      (1.98; 1.04-4.09), and alcohol use (1.82; 1.03-3.23) also was associated with GLB
      orientation. Model II, Lifetime Frequencies of Behaviors, showed that frequency
      of crack cocaine use (1.38; 1.06-1.79), inhalant use (1.30; 1.05-1.61), and
      number of sexual partners (1.27; 1.06-1.43) was associated with GLB orientation.
      Model III, Frequency of Recent Behaviors, showed smokeless tobacco use in the
      past 30 days (1.38; 1. 20-1.59) and number of sexual partners in the previous 3
      months (1. 47; 1.31-1.65) were associated with GLB orientation. Model IV,
      Frequency of Behaviors at School, showed having one's property stolen or
      deliberately damaged (1.23; 1.08-1.40) and using marijuana (1.29; 1.05-1.59) and
      smokeless tobacco (1.53; 1.30-1.81) were associated with GLB orientation.
      Overall, GLB respondents engaged disproportionately in multiple risk behaviors,
      reporting an increased mean number of risk behaviors (mean = 6.81 +/- 4.49)
      compared with the overall student population (mean = 3.45 +/- 3.15). CONCLUSION:
      GLB youth who self-identify during high school report disproportionate risk for a
      variety of health risk and problem behaviors, including suicide, victimization,
      sexual risk behaviors, and multiple substance use. In addition, these youth are
      more likely to report engaging in multiple risk behaviors and initiating risk
      behaviors at an earlier age than are their peers. These findings suggest that
      educational efforts, prevention programs, and health services must be designed to
      address the unique needs of GLB youth.

PMID- 9565423
TI  - Low serum thyroxine on initial newborn screening is associated with
      intraventricular hemorrhage and death in very low birth weight infants.
AB  - Transient hypothyroxinemia (TH) of prematurity has been correlated with poor
      neurodevelopmental outcome. However, the relationship between thyroid function
      and neonatal mortality and brain injury has not been described. OBJECTIVE: To
      investigate the relationship between thyroid function and neonatal outcome.
      METHODS: Review of infants weighing <1500 grams admitted to a single level III
      newborn intensive care unit (n = 342). Serum total T4 values of initial newborn
      screening of infants dying before hospital discharge were compared with those of
      surviving infants. Total T4 values from infants with and without intraventricular
      hemorrhage (IVH) and periventricular leukomalacia (PVL) also were compared.
      RESULTS: T4 values strongly correlated with gestational age (r = .56). Overall,
      289 (85%) of 342 infants had TH. None of the infants had true congenital
      hypothyroidism. T4 values of infants with cystic PVL (n = 15) were not
      statistically different from those for infants who did not develop cystic PVL.
      Infants with IVH (n = 58) had a lower T4 value than did infants who did not
      develop IVH (5.4 +/- 3.4 microg/dL vs 7.8 +/- 3.6 microg/dL). Infants who died
      before hospital discharge (n = 24) had a lower T4 value than did infants
      discharged to home (3.4 +/- 2.2 vs 7.9 +/- 3.7 microg/dL). After controlling for
      potential confounding variables, T4 value remained associated with an increased
      odds of IVH (odds ratio: 1.2; 95% confidence interval: 1.05 to 1.4) and mortality
      (odds ratio: 2.3; 95% confidence interval 1.6 to 3.4). CONCLUSIONS: In our
      population of very low birth weight infants, TH has an incidence of 85%. Very low
      T4 values on initial newborn screening are associated with increased odds of
      death and IVH. Additional investigation is needed to determine whether low serum
      thyroxine level contributes to IVH and neonatal death or whether it is simply an
      associated factor.

PMID- 9565424
TI  - Cystic fibrosis: when should high-resolution computed tomography of the chest Be
      obtained?
AB  - OBJECTIVE: To provide indications for high-resolution computed tomography (HRCT)
      of the chest in patients with cystic fibrosis (CF). DESIGN: We compared the HRCT
      and conventional chest radiography (CCR) scores and assessed their correlation
      with clinical scores and pulmonary function tests. SETTING: Department of
      Pediatrics, Federico II University, Naples, Italy. SUBJECTS: A total of 30
      patients with CF 6.75 to 24 years of age. RESULTS: CCR scores correlated highly
      with HRCT (r = -0.8) and clinical (r = 0.5) scores, whereas total HRCT scores
      were not related to clinical scores. Of all the specific HRCT findings, only
      bronchiectasis appeared related significantly to the clinical score (r = 0.6).
      Most pulmonary function tests were related to CCR and total HRCT scores, but not
      to HRCT scoring of specific changes. Forced vital capacity and CCR scores
      appeared the best predictors of the HRCT score (multiple R = 0.58 and 0.79,
      respectively). In patients with mild lung disease, HRCT detected bronchiectasis
      and air trapping in 57% and 71% of the cases, respectively. In patients with more
      abnormal chest radiographs, bronchiectasis and air trapping were demonstrated on
      HRCT in all cases. CONCLUSIONS: These findings suggest that HRCT of the chest is
      most useful in the identification of early lung abnormalities in patients with CF
      with mild respiratory symptoms, whereas for established disease, CCR is still the
      first-line imaging technique. The advantage of detecting early changes on CT
      imaging awaits additional confirmation, at least until early therapeutic
      interventions affecting significantly the final outcome of the disease are
      demonstrated. In patients with advanced disease, HRCT may be useful in the
      evaluation of specific lung changes when more aggressive treatment such as chest
      surgical interventions is indicated. Given the cost of the procedure and the high
      radiation dosage compared with CCR, a careful assessment of the cost:benefit
      ratios of HRCT is strongly recommended in CF.

PMID- 9565425
TI  - Four cases of severe hepatotoxicity associated with pemoline: possible autoimmune
      pathogenesis.

PMID- 9565426
TI  - Point mutation in exon 12 of the receptor tyrosine kinase proto-oncogene RET in
      Ondine-Hirschsprung syndrome.
AB  - A 5-year-old girl with congenital central hypoventilation syndrome associated
      with Hirschsprung's disease (Ondine-Hirschsprung syndrome) representing a
      missense mutation in exon 12 of the receptor tyrosine kinase (RET) proto-oncogene
      is reported. Using a direct sequencing technique, genomic DNA obtained from the
      patient's peripheral leukocytes was analyzed for its nucleotide sequences in all
      20 exons of the RET proto-oncogene, seven regions of the 1st to the 7th exon of
      the endothelin-B receptor gene and endothelin 3 gene, including sequences
      corresponding to proteolytic cleavage sites. The analysis revealed that adenine
      at the 2116th base in the 12th exon in the RET proto-oncogene was substituted by
      guanine, supposedly resulting in a mutation of Thr 706 to Ala. No other
      mutational change was observed in the gene examined in this case. Mutation
      analysis has not been described previously on the gene in this disease complex.
      Mutation in this case might impair the maturation of the tyrosine kinase protein
      and subsequently cause neurocristopathy supposedly originating from the neural
      crest.

PMID- 9565427
TI  - Minocycline-induced lupus in adolescents.

PMID- 9565428
TI  - Growth hormone deficiency in patients with 22q11.2 deletion: expanding the
      phenotype.
AB  - The list of findings associated with the 22q11.2 deletion is quite long and
      varies from patient to patient. The hallmark features include: conoruncal cardiac
      anomalies, palatal defects, thymic aplasia or hypoplasia, T cell abnormalities,
      mild facial dysmorphia, and learning disabilities. The 22q11.2 deletion has been
      seen in association with the DiGeorge sequence, velocardiofacial syndrome (VCFS),
      conotruncal anomaly face syndrome, isolated conotruncal cardiac anomalies, and
      some cases of autosomal dominant Optiz G/BBB syndrome. Short stature has been
      seen in one to two thirds of children reported in the literature with a diagnosis
      of VCFS, but growth hormone deficiency (GHD) has not been described in
      conjunction with this diagnosis. We present 4 patients with a 22q11.2 deletion
      and short stature who were found to have abnormalities in the growth hormone
      insulin-like growth factor I axis. All had growth factors less than -2 SD for age
      and failed provocative growth hormone testing. Two patients were found to have
      abnormal pituitary anatomy. In our population, the incidence of GHD in 4 or 95
      children with 22q11 deletion is significantly greater than the estimated
      incidence of GHD in the general population. Children with a 22q11.2 deletion
      appear to be at a greater risk for pituitary abnormalities. Therefore, those
      children with the 22q11.2 deletion and short stature or poor growth should be
      evaluated for GHD, as replacement growth hormone therapy may improve their growth
      velocity and final height prediction.

PMID- 9565429
TI  - Human immunodeficiency virus/acquired immunodeficiency syndrome education in
      schools. American Academy of Pediatrics. Committee on Pediatric AIDS.
AB  - The human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      epidemic has grown during the past 15 years. Education remains a critical
      component of our efforts to prevent HIV infection/AIDS in school children and
      young adults. To accomplish this goal, school personnel should receive updated
      information about HIV infection/AIDS so that accurate teaching on this topic can
      be included in the K-12 health education curriculum. Informed pediatricians and
      nurses can serve as important resources for school health services and
      administration to provide current information for the curriculum. Each community
      should have a school health advisory committee that enlists community support and
      provides input to health education programs in schools.

PMID- 9565430
TI  - The emergency physician and the office-based pediatrician: an EMSC team. American
      Academy of Pediatrics. Committee on Pediatric Emergency Medicine.
AB  - In a quality and cost-conscious health care environment, the pediatrician and
      emergency physician must work as a team. This statement clarifies important
      issues of this relationship, including coordination of patient care,
      communication between clinicians, provision of continuity care, and
      responsibility for quality emergency care.

PMID- 9565431
TI  - Counseling the adolescent about pregnancy options. American Academy of
      Pediatrics. Committee on Adolescence.
AB  - When consulted by a pregnant adolescent, pediatricians should be able to make a
      timely diagnosis and to help the adolescent understand her options and act on her
      decision to continue or terminate her pregnancy. Pediatricians may not impose
      their values on the decision-making process and should be prepared to support the
      adolescent in her decision or refer her to a physician who can.

PMID- 9565432
TI  - The role of the pediatrician in rural EMSC. American Academy of Pediatrics.
      Committee on Pediatric Emergency Medicine.
AB  - In rural America pediatricians can play a key role in the development,
      implementation, and ongoing supervision of emergency medical services for
      children (EMSC). Often the only pediatric resource for a large region, rural
      access pediatricians are more likely to treat pediatric emergencies in their own
      offices, and are a vital resource for rural physicians, or other rural health
      care professionals (physician assistants, nurse practitioners), and emergency
      medical technicians (EMTs) to improve system-wide EMSC by providing education
      about issues from prevention to rehabilitation, technical assistance in protocol
      writing, hospital care, and dat accumulation, and as advocates for community and
      state legislation to support the goals of EMSC.

PMID- 9565433
TI  - Implementation principles and strategies for Title XXI (State Children's Health
      Insurance Program). Academy of Pediatrics. Committee on Child Health Financing.
AB  - A major provision of the Balanced Budget Act of 1997 established the State
      Children's Health Insurance Program (Title XXI of the Social Security Act). This
      program is a historic milestone in the financing of health care for children. Not
      since the enactment of Medicaid has there been a greater investment in children's
      health care. Title XXI does not create universal coverage for all children, but
      this program does offer an unprecedented opportunity to expand insurance ot a
      large portion of uninsured children. Title XXI of the Social Security Act makes
      >$40 billion in federal grants available to states over the next 10 years to
      provide health insurance coverage, including Medicaid. However, states mus
      contribute a defined share of funds to obtain federal matching funds. The
      legislation gives great flexibility to states in designing and implementing their
      programs, and it is critical that they do this in a timely manner. If states fail
      to use all State Children's Health Insurance Program funds available, it is
      possible that future federal funding will be reduced. If this happens, a major
      opportunity to improve health insurance coverage of America's children will be
      diminished.

PMID- 9565434
TI  - Control of hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient
      newborns using an inhibitor of bilirubin production, Sn-mesoporphyrin.
AB  - BACKGROUND: Hyperbilirubinemia in new-borns with glucose-6-phosphate
      dehydrogenase (G6PD) deficiency is a serious clinical problem because of the
      severity and unpredictability of its course. An innovative approach to this
      problem is suggested by previous experience with Sn-mesoporphyrin (SnMP), a
      potent inhibitor of bilirubin production, in moderating neonatal
      hyperbilirubinemia caused by ABO incompatibility, immaturity, and unspecified
      mechanisms. OBJECTIVE: To compare the effectiveness of the preventive and
      therapeutic uses of SnMP in ameliorating the course of bilirubinemia of G6PD
      deficient neonates. METHODS: Neonates born at the Metera Maternity Hospital,
      Athens, Greece, and found to be G6PD-deficient by cord blood testing were
      stratified by sex and gestational age (210-265 days and >265 days) and randomized
      in pairs to receive SnMP (6 micromol/kg birth weight, intramuscularly) either on
      the first day of life (preventive use) or if and when the plasma bilirubin
      concentration (PBC) level reached an age-specific threshold level for
      intervention (therapeutic use). In the case of failure of SnMP to control the
      rise of PBC levels, the protocol defined precisely the threshold PBC levels for
      switchover to phototherapy (PT) and, if necessary, exchange transfusion. PBC was
      measured daily until a declining value was obtained and the case was closed.
      RESULTS: A total of 86 G6PD-deficient neonates were randomized: 42 in the
      preventive arm and 44 in the therapeutic arm. Of the latter, 20 (45%) reached PBC
      levels requiring therapeutic intervention and thus received SnMP. Regardless of
      the trial arm, none of the 86 neonates required PT, whereas in a previous study
      in the same population, 33% of G6PD-deficient neonates required PT. In the
      intrapair sequential analysis, the favored arm was decided on the criterion of
      the age at closure of the case being shorter by at least 1 day. After plotting 30
      untied pairs in the sequential analysis graph, the preventive use of SnMP proved
      to be the favored arm, and the trial was stopped. At this point, there were 2
      unpaired neonates, 12 tied pairs, 22 pairs in which the preventive use of SnMP
      was favored and 8 pairs in which the therapeutic use of SnMP was favored. In the
      group analysis, infants in the preventive group, compared with those in the
      therapeutic group, had a lower maximum PBC level (8.2 +/- 3.1 and 10.9 +/- 2.8
      mg/dL, respectively), which was reached at an earlier age (63.5 +/- 34.8 and 82.2
      +/- 24.7 hours, respectively) as well as a lower closing PBC level (7.2 +/- 2.9
      and 9.6 +/- 2.5 mg/dL, respectively) and an earlier age at closing (89.1 +/- 35.6
      and 110.8 +/- 23.6 hours, respectively). Moreover, a PBC level of >/=8.0 mg/dL, a
      level at which jaundice is clearly visible, was not reached by 52% of the
      neonates in the preventive arm and 16% of the neonates in the therapeutic arm.
      CONCLUSIONS: In G6PD-deficient neonates, a single dose of SnMP administered
      preventively or therapeutically entirely supplanted the need for PT to control
      hyperbilirubinemia. The preventive use of SnMP offers practical advantages in
      populations with a high enough prevalence of G6PD deficiency to justify cord
      blood screening.

PMID- 9565435
TI  - Effects of exposure to alcohol in mother's milk on infant sleep.
AB  - OBJECTIVE: To test the hypothesis that exposure to alcohol in breast milk affects
      infants' sleep and activity levels in the short term. METHODS: Thirteen lactating
      women and their infants were tested on 2 days, separated by an interval of 1
      week. On each testing day, the mother expressed 100 mL of milk, while a small,
      computerized movement detector called an actigraph was placed on the infant's
      left leg to monitor sleep and activity patterning. After the actigraph had been
      in place for approximately 15 minutes, the infants ingested their mother's breast
      milk flavored with alcohol (32 mg) on one testing day and breast milk alone on
      the other. The infants' behaviors were monitored for the next 3.5 hours. RESULTS:
      The infants spent significantly less time sleeping during the 3.5 hours after
      consuming the alcohol-flavored milk (78.2 minutes compared with 56.8 minutes
      after feeding alcohol in breast milk). This reduction was apparently attributable
      to a shortening in the longest sleeping bout (34.5 compared with 56.7 minutes for
      sleeping after breast milk alone) and the amount of time spent in active sleep
      (25.8 minutes compared with 44.2 minutes after breast milk alone); the decrease
      in active sleep was observed in all but 2 of the 13 infants tested. CONCLUSIONS:
      Although the mechanisms underlying the reduction in sleep remain to be
      elucidated, this study shows that short-term exposure to small amounts of alcohol
      in breast milk produces distinctive changes in the infant's sleep-wake
      patterning.

PMID- 9565436
TI  - Adverse effects of high-dose vitamin A supplements in children hospitalized with
      pneumonia.
AB  - OBJECTIVE: To test the hypothesis that high-dose vitamin A supplements will
      enhance recovery of children hospitalized for the treatment of community-acquired
      pneumonia. DESIGN: We conducted a randomized, double-blind, placebo-controlled
      clinical trial of high-dose vitamin A supplements among children 3 months to 10
      years of age (N = 95) admitted to hospital with community-acquired pneumonia in
      Lima, Peru. Children </=1 year of age received 100 000 IU of water-miscible
      vitamin A on admission to the hospital and an additional 50 000 IU the next day.
      Children >1 year of age received 200 000 IU on admission and 100 000 IU the next
      day. RESULTS: Children receiving vitamin A (n = 48) had lower blood oxygen
      saturation (the mean difference on day 3 in hospital was 1.1%), higher prevalence
      rates of retractions (37% in the vitamin A group vs 15% in the placebo group on
      day 3), auscultatory evidence of consolidation (28% in the vitamin A group vs 17%
      in the placebo group on day 3), and were more likely to require supplemental
      oxygen (21% in the vitamin A group vs 8% in the placebo group on day 3) than
      children in the placebo group (n = 47). Adjustment for baseline severity of
      disease and nutritional status did not alter the association of vitamin A with
      increased clinical severity, although the difference in blood oxygen saturation
      was no longer statistically significant. No differences were seen in duration of
      hospitalization or in chest x-ray changes 14 days after admission. No deaths
      occurred, and toxicity of vitamin A was not seen. CONCLUSIONS: This study
      indicates that high-dose vitamin A supplements cause modest adverse effects in
      children recovering from pneumonia and should not be used therapeutically in such
      patients unless there is clinical evidence of vitamin A deficiency or concurrent
      measles infection.

PMID- 9565437
TI  - Attitudes of the physician membership of the society for adolescent medicine
      toward medical abortions for adolescents.
AB  - OBJECTIVE: To document the practices and attitudes of the US physician members of
      the Society for Adolescent Medicine (SAM) regarding adolescent abortion and
      contraception, as well as physician willingness to prescribe medical abortion if
      approved by the Food and Drug Administration (FDA). DESIGN: Cross-sectional
      questionnaire survey. Participants. The entire physician membership of SAM (N =
      1001) was surveyed. A total of 713 physicians responded, with 668 usable surveys
      yielding an adjusted response rate of 70%. RESULTS: Of the respondents, 81% were
      trained as pediatricians; 58% had additional adolescent medicine training. Ninety
      six percent prescribed contraception for their patients. Sixty-one percent of
      respondents identified abortion as an option for pregnant adolescents in all
      circumstances, whereas 4% believed abortion should never be an option. Eighty
      nine percent referred their patients for abortions; 90% were aware of medications
      to induce abortions medically. If these medications (methotrexate and
      misoprostol, RU-486) were FDA-approved, 42% would prescribe them for their
      patients; 34% were unsure. Fifty-four percent believed if medical abortions were
      routinely available, they should be available from primary care physicians.
      Physicians were significantly more likely to consider prescribing medical
      abortions if the physician were female, offered postcoital contraception,
      performed Norplant insertions, referred adolescents for abortions, or performed
      postabortion medical checkups. Physicians were no more likely to consider
      prescribing medical abortions according to physician age, specialty training, or
      date of residency training. Religious affiliation per se was not associated with
      likelihood of prescribing medical abortions, but Catholic physicians were
      significantly less likely to consider prescribing medical abortions. CONCLUSIONS:
      Virtually all SAM physician respondents (96%) reported that abortion for pregnant
      adolescents should be available under some circumstances. Forty-two percent would
      prescribe medical abortion if the medications were FDA-approved, suggesting that
      medical abortion would potentially be available to adolescents from a larger
      group of physicians than is currently available.

PMID- 9565438
TI  - Do missed opportunities stay missed? A 6-month follow-up of missed vaccine
      opportunities in inner city Milwaukee children.
AB  - OBJECTIVES: To determine 1) the frequency of missed vaccine opportunities (VOs)
      in inner city children </=3 years of age; 2) whether the recommended vaccine(s)
      were given within 6 months of the missed opportunity (MO); 3) whether these
      vaccinations were age-appropriate according to the guidelines of the Advisory
      Committee on Immunization Practices; and 4) variables associated with MOs.
      DESIGN: Retrospective chart review with a nested retrospective cohort of children
      with MOs. SETTING: Two inner city practice settings in Milwaukee: a community
      health center and an academic continuity care practice. PATIENTS/SELECTION
      PROCEDURE: A consecutive sample of 710 visits of inner city children </=3 years
      of age with VOs, seen between January 1 and March 31, 1995. A VO was defined as
      any encounter when the child was vaccine-eligible according to Advisory Committee
      on Immunization Practices guidelines. RESULTS: MOs occurred in 47% (330/710) of
      the VOs. Only 40% of the children with MOs received age-appropriate immunizations
      within 6 months; 30% received the vaccinations beyond the age-appropriate time.
      The remaining 30% either did not return or were not vaccinated on return. The
      variables significantly associated with MOs were 1) age: children with MOs were
      older than those without, with a mean age of 15.5 months vs 10.9 months; 2) minor
      febrile illness; 3) moderate/severe illness; 4) acute illness encounters; and 5)
      patient's being seen at the community health center. Only 15.5% of all MOs were
      justified by the presence of moderate/severe illness. CONCLUSIONS: VOs are
      frequently missed in inner city children. Most of the MOs were not justified by
      the valid contraindication of moderate/severe illness. Sixty percent of the
      children with MOs did not receive age-appropriate immunizations within 6 months.
      These children are vulnerable to vaccine-preventable diseases such as measles and
      pertussis.

PMID- 9565439
TI  - Anabolic steroid use by male and female middle school students.
AB  - BACKGROUND: The prevalence of anabolic steroid use by high school and college
      students has been reported in the literature. However, rumors persist regarding
      the use of steroids by younger populations. OBJECTIVE: To assess the extent of
      steroid use by male and female middle school students and to explore their
      attitudes and perceptions about these drugs. Methods. A confidential self-report
      questionnaire was administered to 466 male and 499 female students between 9 and
      13 years of age (mean +/- SD, 11.4 +/- 0.9 years) in 5th, 6th, and 7th grades
      from four public middle schools in Massachusetts. The number of students
      reporting steroid use and differences between users' and nonusers' underlying
      attitudes and perceptions about these drugs were evaluated. RESULTS: The response
      rate was 82% (965/1175 eligible). Results indicated that 2.7% of all middle
      school students reported using steroids; 2.6% were males and 2.8% were females.
      When steroid users were compared with nonusers, 47% versus 43% thought that
      steroids make muscles bigger; 58% versus 31% thought that steroids make muscles
      stronger; 31% versus 11% thought that steroids improve athletic performance; 23%
      versus 13% thought that steroids make one look better; 23% versus 9% knew someone
      their own age who currently took steroids; 38% versus 4% were asked by someone to
      take steroids; 54% versus 91% thought that steroids were bad for them; and 35%
      versus 2% indicated that they would take steroids in the future. Additional
      analyses determined steroid user involvement in sports and activities.
      CONCLUSION: The results of this study suggest that the problem of illicit steroid
      use extends to children and young adolescents and that a segment of this
      population is mindful of the potential physiologic effects of steroids. This
      information will be useful to pediatricians, sport authorities, and school
      teachers whose guidance will become increasingly more important as steroid
      educational interventions for male and female middle school students are
      developed.

PMID- 9565440
TI  - Early dexamethasone therapy in preterm infants: a follow-up study.
AB  - OBJECTIVES: To study the outcome at 2-year corrected age of infants who
      participated in a double-blind controlled trial of early (<12 hours)
      dexamethasone therapy for the prevention of chronic lung disease (CLD). METHODS
      AND MATERIALS: A total of 133 children (70 in the control group, 63 in the
      dexamethasone-treated group) who survived the initial study period and lived to 2
      years of age were studied. All infants had birth weights of 500 to 1999 g and had
      severe respiratory distress syndrome requiring mechanical ventilation within 6
      hours after birth. For infants in the treatment group, dexamethasone was started
      at a mean age of 8.1 hours and given 0.25 mg/kg every 12 hours for 1 week and
      then tapered off gradually over a 3-week period. The following variables were
      evaluated: interim medical history, socioeconomic background, physical growth,
      neurologic examinations, mental and psychomotor development index score (MDI and
      PDI), pulmonary function, electroencephalogram, and auditory and visual evoked
      potential. RESULTS: Infants in the control group tended to have a higher
      incidence of upper respiratory infection and rehospitalization than did the
      dexamethasone-treated group because of respiratory problems. Although there was
      no difference between the groups in somatic growth in girls, the dexamethasone
      treated boys had significantly lower body weight and shorter height than the
      control boys (10.7 +/- 3.0 vs 11.9 +/- 2.0 kg; 84.9 +/- 5.7 vs 87.5 +/- 4.8 cm).
      The dexamethasone-treated group had a significantly higher incidence of
      neuromotor dysfunction (25/63 vs 12/70) than did the control group. The
      dexamethasone-treated infants also had a lower PDI score (79 +/- 26) than did the
      control group (87 +/- 23), but the difference was not statistically significant.
      Both groups were comparable in MDI, incidence of vision impairment, and auditory
      and visual evoked potential. Significant handicap, defined as severe neurologic
      defect and/or intellectual defect (MDI and/or PDI </= 69), was seen in 22
      children (31.4%) in the control group and 26 (41.2%) in the dexamethasone-treated
      group. CONCLUSIONS: Although early postnatal dexamethasone therapy for 4 weeks
      significantly reduces the incidence of CLD, this therapeutic regimen cannot be
      recommended at present because of its adverse effects on neuromotor function and
      somatic growth in male infants, detected at 2 years of age. A longer follow-up is
      needed. If early dexamethasone therapy is to be used for the prevention of CLD,
      the therapeutic regimen should be modified. The proper route of administration,
      the critical time to initiate the therapy, and the dosage and duration of therapy
      remain to be defined further.

PMID- 9565442
TI  - Valproate therapy does not deplete carnitine levels in otherwise healthy
      children.
AB  - OBJECTIVE: To determine whether children with epilepsy undergoing valproate (VPA)
      antiepileptic therapy and who are otherwise healthy have a lower serum level of
      carnitine (CAR) and a higher plasma level of plasma ammonia than do normal
      children. METHODOLOGY: A total of 45 children with epilepsy, 6.3 to 21.7 years of
      age, who were treated solely with VPA and were free of abnormal neurologic
      findings or nutritional problems were randomly selected (VPA-treated group). An
      age-matched control group (n = 45) was selected from subjects without epilepsy
      (control group). Total (T) and free (F) serum CAR, serum VPA concentration, and
      the plasma ammonia level were measured and analyzed. RESULTS: Serum VPA
      concentration exhibited a weak negative correlation with both T- (r = -0.34) and
      F-CAR (r = -0.41). The T-CAR levels were 55.7 +/- 12.4 and 57.6 +/- 12.1 mM, and
      the F-CAR levels 42.7 +/- 9.9 and 44.4 +/- 9.9 mM in the VPA-treated and control
      groups, respectively. Thus, there was no significant difference in T- or F-CAR
      levels between the VPA-treated and control groups. Plasma ammonia levels were the
      same in the two groups: 26 +/- 9.2 and 29.4 +/- 11.8 mM in the VPA-treated and
      control groups, respectively. There was no significant correlation between blood
      ammonia and either T- (r = +0.024) or F-CAR (r = -0. 026). CONCLUSION: Children
      on a regular diet ingest a sufficient amount of CAR that more than meets their
      daily CAR requirement. The level of neither T- nor F-CAR in patients with
      epilepsy and without severe neurologic or nutritional problems being treated with
      VPA appeared to be affected by VPA therapy. Because the blood CAR level depends
      on nutritional condition rather than on blood VPA concentration, CAR deficiency
      caused by VPA is not likely to occur in this population. The usefulness of
      supplementation of CAR for this type of patient with epilepsy, therefore, must be
      reevaluated carefully.

PMID- 9565441
TI  - Self-reported adherence, management behavior, and barriers to care after an
      emergency department visit by inner city children with asthma.
AB  - OBJECTIVE: The inability to adhere to a prescribed therapeutic program for the
      treatment of a chronic disease may be responsible in part for continued disease
      activity. This problem may be more of an issue in the treatment of asthma, a
      common, potentially lethal chronic condition in which the lack of symptoms may be
      interpreted as remission. Adherence was one of the key areas of interest for the
      National Cooperative Inner-City Asthma Study. The focus of this study was to
      identify those issues reported by families that could adversely affect their
      adherence to an asthma care program. The identification of barriers to adherence
      could then form the basis of a successful intervention program. This study
      describes barriers to adherence, asthma management behavior, and self-reported
      adherence. METHODS: Patients presenting during an acute attack of asthma at an
      emergency department (ED) were recruited for this study. The medical record of
      the ED encounter was abstracted and compared with information that was obtained
      during a baseline interview 3 to 5 weeks later. During the baseline interview,
      parents were asked about health care behaviors related to adherence. RESULTS:
      There were 344 children 4 to 9 years of age living in inner city census tracts in
      the study. Four areas of adherence (medicine use, appointment-keeping, emergency
      actions, and asthma attack prevention) were investigated. The parental report of
      medications prescribed at the ED and the information on the abstracted ED report
      agreed 94.9% of the time for the beta-agonists, 86.8% for steroids, and 69.4% for
      cromolyn. Among respondents, 85.4% of parents reported that they are able to
      follow the ED recommendations almost all of the time; side effects of medicines
      were a concern for 81.1% of caretakers who were adherent and for 89.5% of
      caretakers who were nonadherent. Doubts regarding the usefulness of medications
      occurred in 34.4% of those considered adherent and 54.2% who admitted
      nonadherence. Medications were forgotten some of the time by 45.2% of the
      children, and 52.8% tried to get out of taking medicine. Appointments for follow
      up care were kept by 69% of those given an appointment in the ED, by an estimated
      60.0% of those who were told specifically to call for an appointment, and by an
      estimated 25.2% of those who were neither given an appointment nor told
      specifically to make one. Only one third of parents report that they were able to
      keep the child away from known asthma triggers nearly all of the time.
      Approximately half avoided allergens; however, only 37.5% reported avoidance of
      cigarette smoke. The use of preventive medicines occurred in 23.5%. Using a
      medicine and taking the child to a physician were reported as the first or second
      action during an acute attack of asthma by 72.1% of respondents. CONCLUSIONS:
      Adherence to an asthma-management program involves a number of areas: medication,
      appointment-keeping, prevention, and applying an emergency plan of action.
      Barriers to adherence may exist in one or all four of these areas, leading to
      ineffective control of asthma. Recommendations are made for improving the patient
      physician partnership to improve adherence.

PMID- 9565443
TI  - Symptomatic splenic hamartoma: case report and literature review.
AB  - An 11-year-old girl with low-grade fever, night sweats, thrombocytopenia, and an
      8-year history of progressive splenomegaly underwent an elective splenectomy.
      Pathologic diagnosis was multiple splenic hamartoma. The patient's symptoms
      resolved after the splenectomy. Since first described by Rokitansky in 1861,
      approximately 140 cases of splenic hamartoma have been described in the
      literature. Most of the splenic hamartomas were discovered incidentally. A
      minority of these lesions were associated with hematologic symptoms such as
      pancytopenia, anemia, and thrombocytopenia. Only 20 of the reported cases of
      splenic hamartoma occurred in pediatric patients. However, compared with the
      adult patients, nearly half of these cases in pediatric patients was associated
      with symptoms. Splenectomy and partial splenectomy have relieved these symptoms.
      With advances in imaging, splenic hamartomas are being discovered with increasing
      frequency. A multimodal radiologic work-up has enabled some cases of splenic
      hamartoma to be diagnosed preoperatively. Inclusion of this benign entity in the
      differential diagnoses of symptomatic splenomegaly in a pediatric patient is
      important in the preoperative management and counseling of the patient and
      family. In patients who have discrete lesions, consideration of this entity
      preoperatively may avoid total splenectomy.

PMID- 9565444
TI  - School-age follow-up of prophylactic versus rescue surfactant trial: pulmonary,
      neurodevelopmental, and educational outcomes.
AB  - BACKGROUND: Exogenous surfactant replacement has improved survival and reduced
      pulmonary complications of prematurity. Improved early outcomes for infants of
      <30 weeks' gestation treated with a strategy of prophylactic versus rescue
      surfactant, if needed, were demonstrated in a multicenter, randomized trial
      conducted between 1985 and 1988. We reevaluated a subset of survivors from this
      trial to determine the pulmonary and neurodevelopmental outcomes at school age.
      METHODS: At 4.5 to 8 years of age, all survivors from one of the three centers
      were located, and 96% were evaluated. The original randomization included
      stratification by center and followed an intention-to-treat methodology in
      assessing the efficacy of prophylactic versus rescue treatment with surfactant.
      The follow-up test battery included a health-assessment questionnaire,
      spirometry, 88% saturation test, neurologic examination, and the McCarthy Scales
      of Children's Abilities (MSCA) and the Conners' Parent Rating Scale-48.
      Educational achievement was determined by school class placement and teachers'
      reports of achievement. RESULTS: Of the 192 children originally enrolled, 154
      survived. Evaluations were performed on 148 of these infants. An abnormal
      pulmonary history was found in 45 (30%) of the children: 16 (22%) in the
      prophylactic group and 29 (39%) in the rescue group. Formal pulmonary function
      was evaluated in 81 children; 29 (78%) in the prophylactic group and 33 (75%) in
      the rescue group were considered abnormal. No significant differences were found
      between the two groups on either cognitive or motor subscales of the MSCA, the
      Conners' Parent Rating Scale-48, the neurologic examination, the education
      services received in school, or the teacher ratings of below-average academic
      performance. Intelligence scores measured on the MSCA were low-normal for both
      groups. Some level of educational assistance was being provided to 72 (49%) of
      the cohort studied, and both groups had below average educational performance and
      increased needs for educational assistance. CONCLUSIONS: Prophylactic surfactant
      administration to infants of <30 weeks' gestation was associated with fewer long
      term clinical pulmonary complications than assignment to rescue administration.
      Formal pulmonary testing at school age did not reveal significant differences
      between treatment groups in those infants who could be tested. There also were no
      group differences found on neurologic, cognitive, behavioral, or educational
      assessments at school age.

PMID- 9565445
TI  - Predictors of mortality from fires in young children.
AB  - BACKGROUND: In the United States in 1994, fires claimed 3.75 lives per 100 000
      child years and accounted for 17.3% of all injury deaths in children <5 years of
      age. OBJECTIVES: To conduct a historical cohort study that uses maternal
      demographic characteristics to identify young children at high risk of fire
      related deaths, thus defining appropriate targets for prevention programs.
      METHODS: The cohort consisted of children born to mothers who resided in the
      state of Tennessee between 1980 and 1995. Information was obtained by linking
      birth certificates, 1990 census data, and death certificates. Children were
      eligible for the study if they were <5 years of age at any time within the study
      period and if key study variables were present (99.2% of births). Birth
      certificates provided information on maternal characteristics including age,
      race, education, previous live births, use of prenatal care, and residence (in
      standard metropolitan statistical area). Child characteristics included gender,
      gestational age, and birth type (singleton/multiple gestation). Neighborhood
      income was estimated by linking the mother's address at the time of birth to the
      1990 census (block group mean per capita income). The study outcome was a fire
      resulting in at least one fatality (fatal fire event) during the study period,
      identified from death certificates (coded E880 through E889 in the International
      Classification of Diseases, 9th rev). We calculated the fatal fire event rate
      corresponding to each stratum of maternal/child characteristics. We assessed the
      independent association between each characteristic and the risk of a fatal fire
      event from a Poisson regression multivariate analysis. RESULTS: During the study
      period, 1 428 694 children contributed 5 415 213 child years to the cohort: there
      were 270 deaths from fire (4.99 deaths per 100 000 child years) and 231 fatal
      fire events. In the multivariate analysis, factors associated with greater than a
      threefold increase in fatal fire events included maternal education, age, and
      number of other children. Compared with children whose mothers had a college
      education, children whose mothers had less than a high school education had 19.4
      times (95% confidence interval [CI], 2.6-142.4) an increased risk of a fatal fire
      event. Children whose mothers had more than two other children had 6.1 times (95%
      CI, 3.8-9.8) an increased risk of a fatal fire event compared with children whose
      mothers had no other children. Children of mothers <20 years of age had 3.9 times
      (95% CI, 2.2-7.1) increased risk of a fatal fire event compared with children
      whose mothers were >/=30 years old. Although both maternal neighborhood income
      and race were associated strongly with increased rates of fatal fire events in
      the univariate analysis, this association did not persist in the multivariate
      analysis. Other factors that were associated with increased risk of fatal fire
      events in the multivariate analysis were male gender and having a mother who was
      unmarried or who had delayed prenatal care. The three factors associated most
      strongly with fire mortality were combined to create a risk score based on
      maternal education (>/=16 years, 0 points; 13 to 15 years, 1 point; 12 years, 2
      points; <12 years, 3 points); age (>/=30 years, 0 points; 25 to 29 years, 1
      point; 20 to 24 years, 2 points; <20 years, 3 points); and number of other
      children (none, 0 points; one, 1 point; two, 2 points; three or more, 3 points).
      The lowest-risk group (score <3) included 19% of the population and had 0.19
      fatal fire events per 100 000 child years. In contrast, highest-risk children
      (score >7) comprised 1.5% of the population and had 28.6 fatal fire events per
      100 000 child years, 150 times higher than low-risk children. Children with risk
      scores >5 contributed 26% of child years but experienced 68% of all fatal fire
      events. If the fatal fire event rate for all children had been equal to that of
      the low-risk group (risk score <3), then 95% of deaths from

PMID- 9565446
TI  - Cat scratch disease presenting with peripheral facial nerve paralysis.
AB  - Acquired peripheral facial nerve paralysis is a relatively common disorder that
      affects both children and adults. The most frequent nontrauma-related etiologies
      in otherwise neurologically intact patients are idiopathic (Bell's palsy) and
      infectious, which includes otitis media, herpes zoster, Lyme disease, herpes
      simplex virus, Epstein-Barr virus, and Mycoplasma pneumoniae. Cat scratch disease
      (CSD) is typically a subacute, regional lymphadenitis caused by Bartonella
      henselae that is seen in children and young adults. CSD most often has a benign,
      self-limited course. However, 11% of CSD patients may present atypically, most
      commonly with Perinaud's oculoglandular syndrome or acute encephalopathy. We
      present a child with the first reported case of acute facial nerve paralysis in
      serologically proven CSD with typical lymphadenitis.

PMID- 9565447
TI  - Hepatorenal syndrome.
AB  - The hepatorenal syndrome is a severe and common complication of patients with
      advanced cirrhosis and ascites. It is characterised not only by renal failure but
      also by marked alterations in systemic haemodynamics. Renal failure is due to a
      marked hypoperfusion of the kidney secondary to renal vasoconstriction. Although
      the pathogenesis of hepatorenal syndrome is not completely understood, it is
      thought to be the extreme manifestation of the underfilling of the arterial
      circulation secondary to an arterial vasodilation, located mainly in the
      splanchnic circulation. Recently, a revised definition and diagnostic criteria of
      hepatorenal syndrome have been proposed. The prognosis of patients with
      hepatorenal syndrome is very poor. Liver transplantation is the only effective
      treatment but it is not applicable in most cases due to short survival. New
      therapies developed during the last years, such as the use of systemic
      vasoconstrictors or transjugular intra-hepatic portosystemic shunts appear to be
      promising, but prospective investigations are needed to delineate their real
      usefulness.

PMID- 9565448
TI  - Nothing but the evidence.

PMID- 9565449
TI  - Most compensation claims concern restorative or oral surgery procedures.

PMID- 9565451
TI  - Analysis of Well Characterized Biotechnology Pharmaceuticals. Conference
      proceedings. San Francisco, California, USA. 6-8 January 1997.

PMID- 9565450
TI  - High-spin states (S >/= 5/2) of the photosystem II manganese complex.
AB  - The Mn4 complex which is involved in water oxidation in photosystem II (PSII) is
      known to exhibit two types of EPR signals in the S2 state, one of the five redox
      states of the enzyme cycle: either a multiline signal (S = 1/2) or a signal at g
      = 4.1 (S = 3/2 or S= 5/2). The S = 1/2 state can be converted to that responsible
      for the g = 4.1 signal upon the absorption of near-infrared (IR) light [Boussac,
      A., Girerd, J.-J., and Rutherford, A.W. (1996) Biochemistry 35, 6984-6989]. It is
      shown here that a third state gives rise to signals at g = 10 and 6. This state
      is formed by IR illumination of the S = 1/2 state at 65 K, a temperature where IR
      illumination leads to the loss of the S = 1/2 signal but to no formation of the g
      = 4.1 state. On the basis of the corresponding decrease of the S = 1/2 state, the
      new state can be trapped in approximately 40% of the PSII centers. Warming of the
      sample above 65 K, in the dark, leads to the loss of the g = 10 and 6 resonances
      with the corresponding appearance of the g = 4.1 signal. It is suggested that the
      IR-induced conversion of the S = 1/2 state into the g = 4.1 state at 150 K
      involves the transient formation of the new state. The new state is attributed to
      a S = 5/2 state of the Mn4 complex (although a S value > 5/2 is also a
      possibility). Spectral simulations indicate an E/D ratio of -0.05 with D </= 1 cm
      1. The resonances at g = 10 and 6 correspond to the gz of the +/-5/2 and +/-3/2
      transition, respectively. The temperature-dependent conversion of this S = 5/2
      state into the g = 4.1 state is proposed to be due to relaxation of the ligand
      environment around the Mn4 cluster that leads to a change in the zero field
      splitting parameters, assuming an S = 5/2 value for the g = 4.1 state. The new
      form of the S2 state reported here may explain some earlier data where the S2
      state was present and yet not detectable as either a S = 1/2 or a g = 4.1 EPR
      signal.

PMID- 9565452
TI  - A practical in vitro sperm-egg binding assay that detects subfertile males.
AB  - A series of in vitro assays of sperm-egg binding were developed to identify
      potentially subfertile roosters. Initial assays used either segments of intact
      hen's egg perivitelline membrane (PVM) placed on a microscope slide or a heat
      solubilized extract of PVM (HS-PVM) dried within a flat-bottomed microwell plate,
      with bound sperm detected with a DNA-specific stain and epifluorescence
      microscopy. An automated assay was developed using prestained sulfosuccinimidyl-7
      amino-4-methylcoumarin-3-acetate-HS-PVM and enumeration of bound sperm with a
      fluorometric microwell plate reader. Four populations of chickens differing in
      fertility were evaluated with the following results: 1) the correlation across
      lines between in vitro sperm binding and fertility was 0.83 (N = 40; p < 0.0001);
      2) correlations with other seminal parameters were low; and 3) the relationship
      between sperm binding and fertility was not linear, but a threshold plot allowed
      identification of males with low binding and low fertility. Motile sperm from
      roosters, turkeys, bulls, humans, mice, rams, and stallions bound in a dose
      responsive manner. Features of binding were revealed by both scanning and
      transmission electron microscopy. Use of this assay to cull males whose semen
      appears normal by traditional modes of analysis but differs in the obligatory
      trait of sperm-egg binding could be of value to avoid expensive progeny testing.

PMID- 9565453
TI  - [Primary pulmonary lymphoma presented as Pasteurella multocida pneumonia].

PMID- 9565454
TI  - [A prospective study on the relationship between body mass index and mortality in
      middle-aged and elderly people in Japan].
AB  - We conducted a prospective study to clarify the relationship between mortality
      and body mass index (BMI) in a middle-aged and elderly population in Japan. The
      subjects included 12,649 people (5,686 males and 6,963 females) aged from 40-69
      years, who were identified by a mail survey between 1987 and 1989, and thereafter
      were followed up from the date of the survey until February 28, 1995. Cox's
      proportional hazards model was used to adjust for age, smoking status, drinking
      habit and occupation, and hazard ratios were calculated for total mortality and
      cancer mortality based on levels of BMI, while using a BMI of 22 to approximately
      24 as a reference level. Results showed a U shaped relationship between BMI and
      total mortality in females. Females demonstrated a minimal total mortality in the
      reference group, but a significantly high hazard ratio in the lowest group of BMI
      < 20 (hazard ratio = 1.95, p < 0.01) and the highest group of BMI > or= 26
      (hazard ratio = 1.71, p < 0.01). On the other hand, males did not demonstrate
      such a U shaped relationship, but instead showed an L shaped relationship between
      BMI and total mortality. Males showed a minimal total mortality at a BMI of 24 of
      approximately 26 (hazard ratio = 0.92), but a significantly high hazard ratio in
      the lowest BMI group (hazard ratio = 1.57, p < 0.01). In contrast, an elevated
      hazard ratio was not observed in the highest BMI group (hazard ratio = 1.05). The
      relationship between BMI and cancer mortality was found to be similar to the
      relationship between BMI and total mortality in both males and females. Our
      findings suggest that moderate overweight may be a sign of good health among both
      middle-aged and elderly men in Japan.

PMID- 9565455
TI  - Osteoporosis Update 1997. Symposium proceedings. Osaka, Japan, 13-16 November
      1997.

PMID- 9565456
TI  - Electronic preprints: what should the BMJ do?

PMID- 9565457
TI  - How much does relapse after one year erode effectiveness of smoking cessation
      treatments? Long-term follow up of randomised trial of nicotine nasal spray.

PMID- 9565459
TI  - Proceedings of the 21st International Symposium on High Performance Liquid Phase
      Separations and Related Techniques. Part II. Birmingham, United Kingdom, 22-27
      June 1997.

PMID- 9565460
TI  - Annual meeting of the Hungarian Society for Microbiology. Szekszard, August 25
      27, 1997. Abstracts.

PMID- 9565458
TI  - Commentary: management of the patient.

PMID- 9565461
TI  - Treatment options for cirrhotic ascites.
AB  - Ascites due to cirrhosis can usually be managed successfully by dietary sodium
      restriction and carefully monitored diuretic therapy. However, paracentesis with
      an albumin infusion is a relatively safe alternative that has gained widespread
      acceptance. Other plasma expanders offer a cheaper alternative to albumin. Other
      recently developed techniques include peritoneovenous shunt and transjugular
      intrahepatic portosystemic stent shunt. Each of these is associated with an
      operative mortality and substantial complications, but for diuretic-resistant
      ascites a peritoneovenous shunt has comparable results to paracentesis/albumin.
      For patients with spontaneously occurring renal failure the prognosis is poor.
      None of the above treatments improves renal function. Management should therefore
      be symptomatic with paracentesis as necessary.

PMID- 9565462
TI  - Transition to managed care, part 1.

PMID- 9565463
TI  - Translocation(3;5)(q21-24;q31-34) in two cases of acute myeloid leukemia and in
      one case of thrombocytosis.

PMID- 9565464
TI  - The early recognition of cardiac insufficiency in the presence of pregnancy.
      1937.

PMID- 9565465
TI  - Issue dedicated to Professor Dr.Med. Nepomuk Zollner on the occasion of his 75th
      birthday.

PMID- 9565466
TI  - SERIN II: Second Symposium on Experimental Rhinology and Immunology of the Nose.
      Rotterdam, The Netherlands, 8-10 February 1996.

PMID- 9565467
TI  - Reduction of Cr, Mo, Se and U by Desulfovibrio desulfuricans immobilized in
      polyacrylamide gels.
AB  - Intact cells of Desulfovibrio desulfuricans, immobilized in polyacrylamide gel,
      removed Cr, Mo, Se and U from solution by enzymatic-mediated reduction reactions.
      Lactate or H2 served as the electron donor and the oxidized Cr(VI), Mo(VI),
      Se(VI) and U(VI) served as electron acceptors. Reduction of the oxidized metal
      species resulted in the precipitation of solid phases of the metals. Metal
      removal efficiencies of 86-96% were achieved for initial concentrations of 1 mM
      Mo, Se, and U and 0.5 mM Cr. Insoluble metal phases accumulated on both the
      surface and the interior of the polyacrylamide gel. In column tests conducted for
      U removal, effluent concentrations less than 20 micrograms L(-1) were achieved
      with initial concentrations of 5 mg L(-1) and 20 mg L(-1) U and residence times
      from 25-37 h. The enzymatic reduction of Cr, Mo, Se, and U by immobilized cells
      of D. desulfuricans may be a practical method for removing these metals from
      solution in a biological reactor.

PMID- 9565468
TI  - Stuart Roath.

PMID- 9565469
TI  - [Petr Kuz'mich Anokhin: a biographic assay (on the 100-th birthday)].

PMID- 9565470
TI  - Cost of care for diabetes in Wisconsin hospitals and ambulatory surgery centers
      in 1996.
AB  - Diabetes mellitus imposes a significant financial burden on Wisconsin's health
      care system. One portion of this burden is attributable to the cost of
      hospitalizing diabetes patients. During 1996 hospital inpatients with a principal
      diagnosis of diabetes generated over $60 million in hospital charges (physician
      fees excluded). Ambulatory surgery patients generated an additional $3.4 million
      in facility charges. This article examines those costs, according to age and
      gender, expected pay source, and by county. It also reports the reasons for
      hospitalization and ambulatory surgery for patients whose principal diagnosis was
      diabetes. Employers, public health professionals, physicians and managed care
      firms are interested in containing the social and personal costs of diabetes
      mellitus. This paper explores the financial burden associated with
      hospitalization and ambulatory surgeries for diabetes in Wisconsin for 1996.

PMID- 9565471
TI  - Lipids in Cardiology. Proceedings of an International Workshop. Dijon, France, 11
      13 April 1996.

PMID- 9565472
TI  - [Progress of the Japanese Pharmacological Society during the period 1987 to
      1997].

PMID- 9565473
TI  - The evolution of a discipline--my life in veterinary medicine.

PMID- 9565474
TI  - The 50th anniversary of the Veterinary Medical Corps Officers of the US Public
      Health Service.

PMID- 9565475
TI  - Proceedings of the 4th South-East Asian Ergonomics Society (SEAES) Conference:
      Ergonomics for Productivity and Safe Work. Bangkok, Thailand, November 21-23,
      1994.

PMID- 9565476
TI  - [Molecular biology and molecular genetics in the field of otorhinolaryngology-
      tumorigenesis and oncogenes].

PMID- 9565477
TI  - Joseph Dancis Festschrift.

PMID- 9565478
TI  - The effect of genotype on response thresholds to sucrose and foraging behavior of
      honey bees (Apis mellifera L.).
AB  - Honey bee foragers were tested for their proboscis extension response (PER) to
      water and varying solutions of sucrose. Returning pollen and nectar foragers were
      collected at the entrance of a colony and were assayed in the laboratory. Pollen
      foragers had a significantly higher probability of responding to water and to
      lower concentrations of sucrose. Bees derived from artificially selected high-
      and low-pollen-hoarding strains were also tested using the proboscis extension
      assay. Returning foragers were captured and tested for PERs0 to 30% sucrose.
      Results demonstrated a genotypic effect on PERs of returnining foragers. The PERs
      of departing high- and low-strain foragers were consistent with those of
      returning foragers. The PERs were related to nectar and water reward perception
      of foragers. High strain bees were more likely to return with loads of water and
      lower concentrations of sucrose than foragers from low pollen strain. Low-strain
      bees were more likely to return empty. We identified a previously mapped genomic
      region that contains a variable quantitative trait locus that appears to
      influence sucrose response thresholds. These studies demonstrate a gene-brain
      behavior pathway that can be altered as a consequence of colony-level selection
      for quantities of stored food.

PMID- 9565479
TI  - [Clinical studies of multiple myeloma and related diseases].

PMID- 9565480
TI  - [Antithymocyte globulin therapy].

PMID- 9565481
TI  - [Present and future aspect of artificial blood].

PMID- 9565482
TI  - [Induction of differentiation of leukemia cells].

PMID- 9565484
TI  - Brain tumours and mobile phones?

PMID- 9565483
TI  - Proceedings of the 14th International EuroPACS Meeting. Heraklion, Crete, Greece.
      3-5 October 1996.

PMID- 9565485
TI  - Tuberculosis morbidity--United States, 1997.
AB  - During 1997, a total of 19,855 cases of tuberculosis (TB) (7.4 cases per 100,000
      population) were reported to CDC from the 50 states and the District of Columbia,
      representing a 7% decrease from 1996 and a 26% decrease from 1992, when the
      number of cases peaked during the resurgence of TB in the United States. This
      report summarizes national TB surveillance data for 1997 and compares it with
      similar data for previous years. The findings indicate that, although the overall
      number of TB cases continued to decrease, trends in the number of reported cases
      and TB case rates differed by geographic area and population characteristics.

PMID- 9565486
TI  - Suicide prevention evaluation in a Western Athabaskan American Indian Tribe--New
      Mexico, 1988-1997.
AB  - Since 1979, suicide and homicide have alternated as the second and third leading
      causes of death among young American Indians and Alaska Natives (AI/ANs). From
      1979 through 1992, suicide rates for AI/ANs in all age groups were approximately
      1.5 times the rates for the overall U.S. population. During 1991-1993, suicide
      rates for AI/ANs aged 15-24 and 25-34 years were 31.7 and 26.6 per 100,000
      population, respectively; males aged 15-34 years accounted for 64% of all AI/AN
      suicides. In the overall U.S. population during 1991-1993, the rates for persons
      in these same age groups were 13.0 and 14.5, respectively. Since 1980, suicide
      has been either the second or third leading cause of death for persons aged 15-24
      years in the overall U.S. population. Although knowledge about suicide among
      AI/ANs has increased, information about the efficacy of suicide prevention and
      intervention programs in general, and specifically in AI/AN communities, is
      scarce. In January 1990, following concern raised by tribal officials in 1988
      about suicide among youth, a Western Athabaskan tribe in rural New Mexico
      implemented a suicide prevention and intervention program that targeted tribal
      members aged 15-19 years. This report summarizes the results of the program
      through 1997 and indicates that rates of suicide and attempted suicide among this
      target population decreased substantially after the program was implemented.

PMID- 9565487
TI  - Rift Valley Fever--East Africa, 1997-1998.
AB  - In December 1997, the Kenya Ministry of Health and the World Health Organization
      (WHO) in Nairobi received reports of 478 unexplained deaths in the North Eastern
      province of Kenya and southern Somalia. Clinical features included acute onset of
      fever and headache associated with hemorrhage (hematochezia, hematemesis, and
      bleeding from other mucosal sites). Local health officials also reported high
      rates of illness and death resulting from hemorrhage among domestic animals in
      the area. This report describes the preliminary results of the outbreak
      investigation and the results of a serologic survey.

PMID- 9565488
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 14-1998. A 49-year-old woman with primary biliary cirrhosis,
      pulmonary opacities, and a pleural effusion.

PMID- 9565489
TI  - Hepatitis B virus infection.

PMID- 9565490
TI  - Hepatitis B virus infection.

PMID- 9565491
TI  - Hepatitis B virus infection.

PMID- 9565492
TI  - Effects of raloxifene in postmenopausal women.

PMID- 9565493
TI  - Effects of raloxifene in postmenopausal women.

PMID- 9565494
TI  - Cardiac troponins in patients with chest pain.

PMID- 9565495
TI  - Cardiac troponins in patients with chest pain.

PMID- 9565496
TI  - Cardiac troponins in patients with chest pain.

PMID- 9565497
TI  - Endocardial fibrosis associated with fenfluramine-phentermine.

PMID- 9565498
TI  - Deletion of thyroid transcription factor-1 gene in an infant with neonatal
      thyroid dysfunction and respiratory failure.

PMID- 9565499
TI  - Case 32-1997: Rocky Mountain spotted fever.

PMID- 9565500
TI  - First, do no harm (pending prior approval)

PMID- 9565501
TI  - In vitro studies on the potential for biological control of Aspergillus flavus
      and Fusarium moniliforme by Trichoderma species. 1. Macroscopical and
      microscopical observations of fungal interactions.
AB  - The possible biological control of the seed-associated fungi, Aspergillus flavus
      and Fusarium moniliforme by Trichoderma species was investigated. A study of the
      fungal growth in dual cultures revealed that four of nine isolates of two
      Trichoderma spp. (T. harzianum and T. viride) inhibited fungal growth. A scanning
      electron microscopical investigation of fungal interactions demonstrated no
      obvious hyphae penetration of A. flavus or F. moniliforme by Trichoderma spp.
      Morphological alteration of Fusarium hyphae with pronounced collapse and the
      production of aberrant conidial heads and microheads by A. flavus were observed.
      The results suggest that mycoparasitism is not the mechanism involved in the
      inhibitory interaction of either A. flavus or F. moniliforme with Trichoderma
      spp.

PMID- 9565502
TI  - Advances in Nephrology and Dialysis. Proceedings of the 28th San Carlo Course.
      Milan, Italy, December 9-11, 1996.

PMID- 9565503
TI  - Biventricular long axis function after repair of tetralogy of Fallot.
AB  - Right ventricular restrictive physiology is common after repair of tetralogy of
      Fallot and relates to exercise performance and symptomatic arrhythmias. In this
      study, we examined biventricular long axis function in an attempt to clarify
      further the mechanical substrate of this phenomenon. We studied prospectively 95
      patients with tetralogy of Fallot (age range 1-44.3 years) at a median of 4.3
      years after repair with Doppler and M-mode echocardiography. Pulmonary arterial,
      tricuspid, and mitral Doppler spectrals and 2-D guided M-mode recordings of
      ventricular minor and long axes were obtained with simultaneous phonocardiogram
      and respirometer recordings. Right ventricular restriction was defined by the
      presence of antegrade pulmonary arterial flow during atrial systole throughout
      the respiratory cycle. Restrictive right ventricular physiology was demonstrated
      in 36 (39%) [group 1] of the 92 patients in whom the data were analyzed. Left
      ventricular function (FS, isovolumic relaxation time and transmitral E wave
      deceleration time) was not different in the two groups (p < 0.1, p < 0.6, and p <
      0.8, respectively). The presence of antegrade diastolic flow shortened the
      pulmonary regurgitation in the restrictive group (PR duration/square root of RR
      10.7 +/- 2.1 vs 12.1 +/- 2.1, p < 0.01). There was delayed onset of shortening
      (97.4 +/- 24 vs 88.8 +/- 24 ms, p = 0.01), and the amplitude of right
      atrioventricular ring excursion, corrected for body surface area, was
      significantly lower during atrial systole in the restrictive group (0.43 +/- 0.15
      vs 0.54 +/- 0.2 cm/m2, p < 0.01). There was also a tendency toward a smaller
      ratio of right to left total atrioventricular ring excursion in the same group
      (1.14 +/- 0.19 vs 1.22 +/- 0.23, p = 0.1). Impaired long axis function in
      patients with restrictive right ventricular physiology following repair of
      tetralogy of Fallot is associated with abnormal diastolic filling and may
      contribute to the long-term cardioprotective effect of restrictive physiology by
      limiting the degree of right ventricular dilatation.

PMID- 9565504
TI  - The histology of the lung in neonates with tricuspid valve disease and gross
      cardiomegaly due to severe regurgitation.
AB  - Lung autopsies from four neonates with Ebstein's anomaly or tricuspid valve
      dysplasia and gross cardiomegaly were examined. The mean cardiothoracic ratio was
      92 +/- 0.5%. The degrees of pulmonary hypoplasia and pulmonary artery
      muscularization were assessed and were compared with those in lungs from four
      controls and four patients with diaphragmatic hernias. Lung and body weight
      ratios and radial alveolar counts, which reflect pulmonary hypoplasia and
      immaturity, were significantly decreased only in patients with diaphragmatic
      hernia. The thickness of the medical muscle layer in small pulmonary arteries was
      greater in patients with diaphragmatic hernia; however, in patients with
      tricuspid valve disease, it was relatively small. Abnormal vascular muscle
      extension was seen only in patients with diaphragmatic hernia. In the cases of
      tricuspid valve disease, although cardiomegaly and lung compression were severe,
      lung hypoplasia and immaturity were not, and neither abnormal medial thickening
      nor extension were found. Our results suggest that, at least in full-term infants
      with tricuspid valve disease, surgical relief of lung compression may improve
      respiratory function, even if the cardiomegaly is severe.

PMID- 9565505
TI  - X-chromosomal (p21) muscular dystrophy and left ventricular diastolic and
      systolic function.
AB  - In order to screen for cardiac abnormalities, we prospectively studied 15
      patients (age 8-25 years, mean 15.5 years) with Duchenne's (DMD) (n = 9) and
      Becker's (BMD) (n = 6) muscular dystrophy using the echocardiogram. Data were
      compared to a control group of 92 healthy individuals (age 7.9-25 years, mean
      14.3 years). Left ventricular filling in diastole showed a different pattern when
      comparing echocardiographic Doppler results in patients and controls: Patients
      had lower peak velocity of early left ventricular diastolic filling (E-vmax)(P <
      0.0001) and smaller time velocity integral of the E-wave (E-tvi)(P < 0.0001). In
      contrast, the atrial component (A-vmax, A-tvi) of diastolic filling in DMD/ BMD
      showed no significant difference to controls. The mean area of the mitral valve
      orifice was significantly larger in patients (P < 0.0001) without presence of
      mitral regurgitation. Systolic left ventricular function was significantly
      impaired in the DMD/BMD group; we found lower heart rate corrected fiber
      shortening velocity VCFc (P < 0.001) and higher peak systolic wall stress (P <
      0.001) in DMD/BMD. In 8 of 15 patients, peak systolic wall stress was above 95th
      percentile of controls. In 6 of 15 patients, VCFc was lower than the 5th
      percentile of controls. Systolic and diastolic myocardial impairment was found
      even in young patients and at low stages of disability--equally among patients
      with DMD or BMD. Diastolic left ventricular impairment predominantly affected the
      early diastolic filling, but atrial compensation was poor. Peak systolic wall
      stress measurements were particularly useful in patients with CMP, reflecting the
      left ventricular afterload.

PMID- 9565506
TI  - Use of platinum microcoils to embolize vascular abnormalities in children with
      congenital heart disease.
AB  - Many vascular anomalies found in children with congenital heart disease can be
      embolized with catheter-delivered steel coils. Platinum microcoils delivered
      through a microcatheter broaden the spectrum of lesions amenable to transcatheter
      closure. Platinum microcoil delivery technique is described, and representative
      cases demonstrating microcoil utility and benefits are presented.

PMID- 9565507
TI  - A comparison between MUGA and echocardiography in patients with muscular
      dystrophy in the early detection of cardiac involvement.
AB  - Muscular dystrophies are a group of sex-linked diseases with frequent myocardial
      involvement. In this study 14 patients with Duchenne Muscular Dystrophy (DMD), 7
      with Becker Muscular Dystrophy (BMD), and 8 female carriers who were asymptomatic
      were evaluated with echocardiography and multigated radionuclide ventriculography
      (MUGA). All showed predominant systolic and minor diastolic left ventricular
      dysfunction determined both by echocardiography and MUGA when compared with
      healthy controls. In conclusion, it is recommended that DMD, BMD, and female
      carriers be evaluated and closely monitored for cardiac functions. Though MUGA
      and echocardiography are both effective and sensitive techniques,
      echocardiography is more convenient for availability and serial evaluation.

PMID- 9565508
TI  - Histopathologic changes in the infundibular septum after balloon pulmonary
      valvuloplasty in tetralogy of Fallot.
AB  - Balloon pulmonary valvuloplasty (BPV) has been applied to tetralogy of Fallot
      (TOF) as a palliative procedure. To investigate the histopathologic changes by
      BPV in the infundibular septum of TOF, we performed histopathologic examinations
      of the infundibular septum resected at corrective surgery. The subjects were 5
      patients with TOF, who underwent BPV at the median age of 2.2 months and the
      corrective surgery at the median age of 15.0 months (BPV group), and 4 patients
      with TOF who had no prior BPV and who underwent the corrective surgery at the
      median age of 14.5 months (control group). There was no significant difference
      between the two groups in the endocardial thickness, myocardial vacuole
      degeneration, or fraction of fibrous and interstitial space. However, the
      specimens from 3 patients in the BPV group had localized dense fibrous lesions in
      the myocardium. The findings in this limited sample suggest that BPV for TOF does
      not produce overall histopathologic alterations such as fibrosis, thick
      endocardium, and myocardial vacuole degeneration, but may sometimes damage the
      myocardium of the infundibular septum resulting in the formation of localized
      dense fibrous lesions. The clinical significance of this damage is still unknown,
      and further cases should be investigated.

PMID- 9565509
TI  - Double-inlet and double-outlet left ventricle in situs inversus.
AB  - Double-outlet left ventricle is a rare congenital cardiac malformation that has
      been traditionally difficult to diagnose accurately. We report a unique case of
      situs inversus totalis, L-loop, double-inlet left ventricle and double-outlet
      left ventricle with pulmonary stenosis, diagnosed mainly by transesophageal
      echocardiography and magnetic resonance imaging.

PMID- 9565511
TI  - Severe cyanosis in a newborn after transvenous pacing wire placement.
AB  - Inadvertent disruption of tricuspid valve apposition by a pacing catheter in a
      neonate is described. Severe cyanosis due to atrial level shunting resulted,
      similar to the pathophysiologic state seen in Ebstein's anomaly.

PMID- 9565510
TI  - Recurrent congenital left atrial aneurysm in a newborn.
AB  - Recurrent congenital left atrial aneurysm presenting in a newborn as cardiac
      tamponade is described. Such a presentation has not been previously reported.

PMID- 9565512
TI  - Reversible second degree atrioventricular block after a severe sickle cell
      crisis.
AB  - Despite the high prevalence of sickle cell disease and trait in the black
      population and its serious potential for microinfarction, there are only a few
      reports on acute myocardial damage during vasoocclusive crisis. We report a
      unique case of transient second degree atrioventricular (A-V) block of Mobitz I
      and II type during a severe sickle cell crisis. Localized high ventricular septum
      hypoperfusion demonstrated by a 99mTc-MIBI radionuclide study and reversible
      echocardiographic wall motion abnormalities in the same area were strong
      indicators for a local ischemic event in the A-V node and His bundle area,
      explaining the observed transient conduction abnormalities. The present report
      draws attention to a potentially lethal complication of sickle cell crisis.

PMID- 9565514
TI  - Dobutamine stress echocardiography in anomalous left coronary artery.
AB  - The evaluation of left ventricular function with dobutamine stress
      echocardiography is described for the first time in a patient with anomalous left
      coronary artery from the pulmonary trunk during the preoperative and
      postoperative periods. This method demonstrated signs of myocardial ischemia that
      were not seen on the resting echocardiogram during the preoperative period and
      ventricular function recovery after surgical intervention.

PMID- 9565513
TI  - Primary mitral valve sarcoma in infancy.
AB  - Primary cardiac sarcoma is a rare tumor, found especially in children,
      particularly in the left side of the heart. This report describes a rare case of
      primary mitral valve sarcoma in a 7-month-old male infant with hemiparesis and
      heart murmur who underwent mitral valve replacement because of excessive invasion
      of the mitral valve by the tumor. The patient remains well, free of recurrence
      and cerebral metastasis, and without adjuvant therapy 18 months after the
      operation.

PMID- 9565516
TI  - Atrial flutter complicating neonatal Coxsackie B2 myocarditis.
AB  - A neonate presented with atrial flutter complicating acute Coxsackie B2
      myocarditis. The tachyarrhythmia was successfully terminated with
      electrocardioversion followed by digoxin administration. The infant survived with
      no long-term cardiac sequelae. Atrial flutter is an unusual complication of
      Coxsackie myocarditis that has not previously been reported.

PMID- 9565515
TI  - Echocardiographic evidence for a ductal tissue sling causing discrete coarctation
      of the aorta in the neonate: case report.
AB  - A neonate presented to our institution with the physical findings of coarctation
      of the aorta. After starting prostaglandin E1 the signs and symptoms resolved
      despite persistent closure of the ductus arteriosus. We present echocardiographic
      evidence to support the contention that a ductal tissue sling contributes to the
      formation of juxtaductal coarctation of the aorta.

PMID- 9565517
TI  - Pulmonary hypertension and trisomy 16.
AB  - An infant girl, born small for gestational age, with abnormal single creases on
      the fifth digits, subsequent severe developmental delay, hypertelorism, bilateral
      equinovalgus deformities, grade IV genitourinary reflux and mild right
      hydronephrosis, was found to have an inverted duplication of the short arm of
      chromosome 16 [46,XX; inv dup (16) (p 13.3-->p 11.2]. The cardiac anomalies
      included a large perimembranous ventricular septal defect (VSD) and a moderate
      sized atrial septal defect (ASD). Cardiac catheterization at 6 months of age
      revealed systemic level pulmonary artery pressure, bilateral pulmonary venous
      desaturation, and in room air a pulmonary/systemic blood flow ratio (Qp/Qs) of
      0.8:1.0, which did not change significantly with administration of oxygen and
      nitric oxide. To our knowledge, this is the first description of early
      nonreactive pulmonary vascular disease in a patient with duplication 16p and a
      large VSD.

PMID- 9565518
TI  - Congenital heart disease in primary ciliary dyskinesia.

PMID- 9565519
TI  - Intrapericardial and cardiac lymphangiomas.

PMID- 9565520
TI  - Leiomyosarcoma on an infant's mitral valve.

PMID- 9565521
TI  - Atomic Force microscopy of neuron networks.
AB  - We imaged uncoated neuron networks by an atomic force microscope in the repulsive
      regime of contact mode. Images of granule cells and their axons have been clearly
      revealed with details smaller than 20 nm. The good stability of the sample and
      the mechanical reproducibility of the microscope allowed the imaging of a neuron
      culture area of several square microns. By combining tens of images, we were able
      to reconstruct a highly defined neuronal network. Furthermore, the images were
      very reproducible over repeated scanning acquisition, demonstrating the
      mechanical and thermal stability of the instrument-sample system.

PMID- 9565523
TI  - Halting the march of the immune defenses.

PMID- 9565522
TI  - Consistency in calibrated backscattered electron images of calcified tissues and
      minerals analyzed in multiple imaging sessions.
AB  - Pure metal standards have been used to calibrate the operating envionment in
      quatitative backscattered electron (BSE) imaging of mineralized tissue, allowing
      comparisons to be made between various mineralization states of bone at the
      microscopic level. It has not previuously been documented that calibration
      procedures produce consistent, reliable results over multiple imaging sessions.
      In this study, BSE images were obtained from bones, pure metals, and a naturally
      occurring mineral in multiple imaging sessions over a six day period. The
      graylevel histogram profile (GHP) from each specimen was analyzed for changes in
      the shape and relative placement on the graylevel spectrum. Computer controlled
      calibration and a restrospective calibration method using pure aluminum and pure
      magnesium-aluminum-zinc demonstrated consistency between imaging sessions.
      Calibrated weighted mean graylevels (WMGLs) for biological meterials had an
      average standard deviation of 5.9 graylevels (2.4% variation) during the course
      of the study. WMGLs for inorganic materials had an average standard deviation of
      0.9 graylevels (0.4% variation). A trend towards increased image brightness, due
      to specimen and/or embedding media degradation, was observed in the biological
      tissues. No increase in rightness was observed for the inorgtanic specimens.
      Kurtosis and skewness tests revealed a slight deviation from normality in all
      specimens, which remained consistent between multiple imaging sessions. These
      results demonstrate the BSE image analysis of bones and mineral can be calibrated
      with negligible precision error allowing comparisons between data within and
      between multiple imaging sessions.

PMID- 9565524
TI  - Anatomy of "regenerating axons".

PMID- 9565526
TI  - Pharma giant creates genomics institute.

PMID- 9565525
TI  - Kennewick Man's trials continue.

PMID- 9565527
TI  - Tamoxifen. 'A big deal,' but a complex hand to play.

PMID- 9565528
TI  - T cells on the mucosal frontline.

PMID- 9565530
TI  - Jumbo gene offers clue to Parkinson's.

PMID- 9565529
TI  - Flying by the seat of their halteres.

PMID- 9565531
TI  - Viruses have many ways to be unwelcome guests.

PMID- 9565532
TI  - One for all and all for one.

PMID- 9565533
TI  - The numbers game for virus-specific CD8+ T cells.

PMID- 9565534
TI  - [Jubilees of the Serbian Medical Society. Golden jubilee--a time of renewal and
      remembrance].
AB  - The Serbian medical association was founded in Belgrade 125 years ago. At that
      time, Serbia was liberated from the Ottoman domination, and was one of some
      thirty existing independent states gaining international recognition in 1878. The
      physicians of the Serbian medical association have shared the fate of their
      people over the past 125 years. This is best illustrated by the fact that Serbia
      lost more than 1,000,000 people in World War I and that every third doctor in
      Serbia lost his life serving his people during the war. This was the highest
      expression of philanthropy, unsurpassed in the history of mankind. The period of
      time after the war, was the time of renewal and commemoration. In that time John
      Maynard Keynes, one of the most outstanding figures in the field of world
      economics, was on the Peace Conference in Paris, after the World War I, in charge
      of estimating war damages and the degree of destruction in the Allied countries,
      but without considering their losses in "human capital"-- the only exception he
      made for Serbia. In his book "The Economic Consequences of the Peace (published
      in 1920) he wrote: "The losses of Serbia, although from a human point of view her
      sufferings were the greatest of all, are not measured pecuniarily by great
      figures, on account of her low economic development." He quoted some
      extraordinary figures of the loss of life--"at above 1,000,000, or more than one
      third of the population of Old Serbia." In the end he concludes: "Of all the
      Allies, Serbian sufferings and losses were proportionately the greatest, and
      after Serbian, the French. In these times, also, according to professor Hichmann
      (Geographical Statistical Atlas 1920) "it was found, when the nations counted
      their losses after the war, that Serb casualties amounted to 23% of her
      population as compared with 3.7% for Great Britain, 8.5% for France and 9.3% for
      Germany. No small nation can suffer a loss such as Serbia, drawn moreover
      entirely from its able-bodied manhood, without coming near the risk of
      extinction. Every single man who could be saved from the debacle strengthened the
      hope for the future.

PMID- 9565535
TI  - [In October 1997 Lieut. Col. of the Medical Service V. V. Kolkutin was appointed
      to the post of head of the Forensic Medical Laboratory of the Ministry of Defense
      of the Russian Federation. Interview by L. L. Galin].

PMID- 9565536
TI  - [Directives from the commander of the Main Military Medical Administration of the
      Ministry of Defense of the Russian Federation].

PMID- 9565537
TI  - [Directives from the commander of the Main Military Medical Administration of the
      Ministry of Defense of the Russian Federation].

PMID- 9565538
TI  - Proceedings of the 24th annual meeting of the International Society on Oxygen
      Transport to Tissue. Dundee, Scotland, August 19-23, 1996.

PMID- 9565539
TI  - Proceedings of the 9th Annual Symposium Transcatheter Cardiovascular
      Therapeutics. Washington, DC, USA. September 24-28, 1997.

PMID- 9565540
TI  - One hundred years of journal publication.

PMID- 9565541
TI  - A 100-year perspective on gastrointestinal motility.
AB  - This contribution to the centennial commemorative issue of the American Journal
      of Physiology: Gastrointestinal and Liver Physiology identifies some of the
      important studies of spontaneous electrical and motor activity in the
      gastrointestinal tract published in the Journal between 1898 and 1996. Emphasis
      is given to the contributions made by Walter B. Cannon, Walter C. Alvarez, Emil
      Bozler, C. Ladd Prosser, and James Christensen.

PMID- 9565542
TI  - Practice guideline for psychiatric evaluation of adults. American Psychiatric
      Association.

PMID- 9565543
TI  - [Apropos of the article by Y. Finkelstein et al.: "Anti-Ro (SSA) and anti-La
      (SSB) antibodies and complete congenital heart block"].

PMID- 9565544
TI  - [Apropos of the article by Y. Finkelstein et al.: "Anti-Ro (SSA) anti-La (SSB)
      antibodies and complete congenital heart block"].

PMID- 9565545
TI  - Use your power to be an advocate for women's health.

PMID- 9565546
TI  - Networking can lead to new career opportunities in perioperative nursing.

PMID- 9565547
TI  - Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss.
AB  - Activation of apoptosis is associated with generation of reactive oxygen species.
      The present research shows that superoxide is produced by mitochondria isolated
      from apoptotic cells due to a switch from the normal 4-electron reduction of O2
      to a 1-electron reduction when cytochrome c is released from mitochondria. Bcl-2,
      a protein that protects against apoptosis and blocks cytochrome c release,
      prevents superoxide production when it is overexpressed. The switch in electron
      transfer provides a mechanism for redox signaling that is concomitant with
      cytochrome c-dependent activation of caspases. The block of cytochrome c release
      provides a mechanism for the apparent antioxidant function of Bcl-2.

PMID- 9565548
TI  - A signal peptide that directs non-Sec transport in bacteria also directs
      efficient and exclusive transport on the thylakoid Delta pH pathway.
AB  - Signal peptides that specifically direct precursor proteins to the thylakoid
      Delta pH pathway possess an N domain RR motif. Signal peptides that direct
      transport of bacterial proteins across a non-Sec export pathway possess an N
      domain RRXFLK consensus motif. Recent genetic studies suggest an evolutionary
      link between these two protein translocation pathways. To further explore this
      relationship, we examined the thylakoid targeting capability of the signal
      peptide for Escherichia coli hydrogenase 1 small subunit (HyaA) by linking it to
      plastocyanin and assaying the chimeric protein in an in vitro thylakoid transport
      assay. The chimeric precursor was transported across thylakoids with high
      efficiency. Transport was characteristic of the Delta pH but not the Sec pathway,
      i.e. it was eliminated by ionophores that dissipate the DeltapH but occurred in
      the absence of stromal extract or ATP. This result was confirmed by competition
      with chemical quantities of a Delta pH pathway precursor. This indicates that the
      HyaA signal peptide has the necessary elements for efficient and exclusive
      targeting to the Delta pH pathway and further supports the notion that the
      alternate targeting pathways in prokaryotes and plant thylakoids are analogous.

PMID- 9565549
TI  - Synthetic signal peptides specifically recognize SecA and stimulate ATPase
      activity in the absence of preprotein.
AB  - Although it is known that virtually all exported proteins require a signal
      peptide, it is not clearly understood how the signal peptide interfaces with the
      translocation machinery to achieve transport. In this study we document a direct
      interaction between the signal peptide and SecA, a primary component of the
      translocase in Escherichia coli, and show that the signal peptide itself can
      stimulate SecA-lipid ATPase activity. Using synthetic signal peptides
      corresponding to the wild type alkaline phosphatase signal sequence and two model
      sequences, we find that the extent of stimulation of SecA ATPase activity by the
      different peptides parallels the hierarchy of results found for in vivo function
      (Izard, J. W., Doughty, M. B., and Kendall, D. A. (1995) Biochemistry 34, 9904
      9912). The peptide-induced activity requires a lipid to protein molar ratio of at
      least 300:1 and liposomes enriched in negatively charged phospholipids.
      Furthermore, specific binding of the signal peptide to SecA was demonstrated
      using chemical cross-linking and competition with unlabeled peptides.

PMID- 9565550
TI  - Structure of peptide deformylase and identification of the substrate binding
      site.
AB  - Peptide deformylase is an essential metalloenzyme required for the removal of the
      formyl group at the N terminus of nascent polypeptide chains in eubacteria. The
      Escherichia coli enzyme uses Fe2+ and nearly retains its activity on substitution
      of the metal ion by Ni2+. We have solved the structure of the Ni2+ enzyme at 1.9
      A resolution by x-ray crystallography. Each of the three monomers in the
      asymmetric unit contains one Ni2+ ion and, in close proximity, one molecule of
      polyethylene glycol. Polyethylene glycol is shown to be a competitive inhibitor
      with a KI value of 6 mM with respect to formylmethionine under conditions similar
      to those used for crystallization. We have also solved the structure of the
      inhibitor-free enzyme at 2.5-A resolution. The two structures are identical
      within the estimated errors of the models. The hydrogen bond network stabilizing
      the active site involves nearly all conserved amino acid residues and well
      defined water molecules, one of which ligates to the tetrahedrally coordinated
      Ni2+ ion.

PMID- 9565551
TI  - Mutation of an active site residue of tryptophan synthase (beta-serine 377)
      alters cofactor chemistry.
AB  - To better understand how an enzyme controls cofactor chemistry, we have changed a
      tryptophan synthase residue that interacts with the pyridine nitrogen of the
      pyridoxal phosphate cofactor from a neutral Ser (beta-Ser377) to a negatively
      charged Asp or Glu. The spectroscopic properties of the mutant enzymes are
      altered and become similar to those of tryptophanase and aspartate
      aminotransferase, enzymes in which an Asp residue interacts with the pyridine
      nitrogen of pyridoxal phosphate. The absorption spectrum of each mutant enzyme
      undergoes a pH-dependent change (pKa approximately 7.7) from a form with a
      protonated internal aldimine nitrogen (lambdamax = 416 nm) to a deprotonated form
      (lambdamax = 336 nm), whereas the absorption spectra of the wild type tryptophan
      synthase beta2 subunit and alpha2 beta2 complex are pH-independent. The reaction
      of the S377D alpha2 beta2 complex with L-serine, L-tryptophan, and other
      substrates results in the accumulation of pronounced absorption bands (lambdamax
      = 498-510 nm) ascribed to quinonoid intermediates. We propose that the engineered
      Asp or Glu residue changes the cofactor chemistry by stabilizing the protonated
      pyridine nitrogen of pyridoxal phosphate, reducing the pKa of the internal
      aldimine nitrogen and promoting formation of quinonoid intermediates.

PMID- 9565552
TI  - Identification of the ligand binding site for the integrin alpha9 beta1 in the
      third fibronectin type III repeat of tenascin-C.
AB  - The integrin alpha9 subunit forms a single heterodimer, alpha9 beta1 that
      mediates cell adhesion to a site within the third fibronectin type III repeat of
      tenascin-C (TNfn3). In contrast to at least 3 other integrins that bind to this
      region of tenascin-C, alpha9 beta1 does not recognize the common integrin
      recognition motif, Arg-Gly-Asp (RGD). In this report, we have used substitution
      mutagenesis to identify a unique ligand recognition sequence in TNfn3. We
      introduced mutations substituting alanine for each of the acidic residues in or
      adjacent to each of the exposed loops predicted from the solved crystal
      structure. Most of these mutations had little or no effect on adhesion of alpha9
      transfected SW480 colon carcinoma cells, but mutations of either of two acidic
      residues in the B-C loop region markedly reduced attachment of these cells. In
      contrast, cells expressing the integrin alphav beta3, previously reported to bind
      to the RGD sequence in the adjacent F-G loop, attached to all mutant fragments
      except one in which the RGD site was mutated to RAA. The peptide, AEIDGIEL, based
      on the sequence of human tenascin-C in this region blocked the binding of alpha9
      transfected cells, but not beta3-transfected cells to wild type TNfn3. This
      sequence contains a tripeptide, IDG, homologous to the sequences LDV, IDA, and
      LDA in fibronectin and IDS in VCAM-1 recognized by the closely related integrin
      alpha4 beta1. These findings support the idea that this tripeptide motif serves
      as a ligand binding site for the alpha4/alpha9 subfamily of integrins.

PMID- 9565553
TI  - Identification and characterization of a novel human aldose reductase-like gene.
AB  - We have identified a novel human protein that is highly homologous to aldose
      reductase (AR). This protein, which we called ARL-1, consists of 316 amino acids,
      the same size as AR, and its amino acid sequence is 71% identical to that of AR.
      It is more closely related to the AR-like proteins such as mouse vas deferens
      protein, fibroblast growth factor-regulated protein, and Chinese hamster ovary
      reductase, with 81, 82, and 83%, respectively, of its amino acid sequence
      identical to the amino acid sequence of these proteins. The cDNA of ARL-1 was
      expressed in Escherichia coli to obtain recombinant protein for characterization
      of its enzymatic activities. For comparison, the cDNA of human AR was also
      expressed in E. coli and analyzed in parallel. These two enzymes differ in their
      pH optima and salt requirement, but they act on a similar spectrum of substrates.
      Similar to AR, ARL-1 can efficiently reduce aliphatic and aromatic aldehydes, and
      it is less active on hexoses. While AR mRNA is found in most tissues studied, ARL
      1 is primarily expressed in the small intestines and in the colon, with a low
      level of its mRNA in the liver. The ability of ARL-1 to reduce various aldehydes
      and the locations of expression of this gene suggest that it may be responsible
      for detoxification of reactive aldehydes in the digested food before the
      nutrients are passed on to other organs. Interestingly, ARL-1 and AR are
      overexpressed in some liver cancers, but it is not clear if they contribute to
      the pathogenesis of this disease.

PMID- 9565554
TI  - Skeletal muscle myosin monomer in equilibrium with filaments forms a folded
      conformation.
AB  - Rabbit skeletal myosin forms stable filaments under physiological conditions, and
      only a small amount stays as a monomer in equilibrium with filaments. The myosin
      monomers were observed in two conformational states, as extended and folded forms
      upon electron microscopy and gel filtration high performance liquid
      chromatography. The fraction of monomers in the folded conformation increased
      with a decrease in the concentration of NaCl below 0.2 M, and the conformational
      state was affected neither by the presence of ATP nor by the phosphorylation of
      regulatory light chain. In most of the folded monomers, the tail bent back toward
      the heads at one region, 45 nm apart from the head-tail junction, and the
      remaining tail portion containing the C-terminal tip appeared to interact with
      the head-tail junction. Only a small percentage of the folded monomers was in a
      more compact conformation close to the 10 S conformation of vertebrate smooth
      muscle and non-muscle myosins. The folded monomers, however, may not trap the
      products of ATP hydrolysis as assessed by single turnover experiments. The
      percentage of monomers in the 10 S-like conformation was increased by the
      exchange of a regulatory light chain with the smooth muscle light chain,
      indicating the participation of head-tail junction, including the regulatory
      light chain in the formation of folded conformation. The folded conformation may
      be common to various myosin IIs, suggestive of common roles for the folded
      monomers.

PMID- 9565555
TI  - Presentation of the Goodpasture autoantigen to CD4 T cells is influenced more by
      processing constraints than by HLA class II peptide binding preferences.
AB  - Class II molecules are believed to influence immune responses by selectively
      binding antigen-derived peptides for recognition by T cells. In Goodpasture's
      (anti-glomerular basement membrane) disease, autoimmunity to the NC1 domain of
      the alpha3-chain of type IV collagen (alpha3(IV)NC1) is strongly associated with
      HLA-DR15. We have examined the influence of the peptide binding preferences of
      DR15 molecules on the selection of alpha3(IV)NC1-derived peptides displayed bound
      to DR15 molecules on the surface of alpha3(IV)NC1-pulsed DR15-homozygous Epstein
      Barr virus-transformed human B cells. The preferences of DR15 molecules were
      investigated using a panel of 24 overlapping peptides spanning the sequence of
      alpha3(IV)NC1. The alpha3(IV)NC1-derived peptides selected for display to T cells
      were determined by biochemical analysis as reported previously (Phelps, R. G.,
      Turner, A. N., and Rees, A. J. (1996) J. Biol. Chem. 271, 18549-18553). Three
      nested sets of naturally presented alpha3(IV)NC1 peptides were detectable bound
      to DR15 molecules. Peptides representative of each nested set bound to DR15
      molecules, but almost two-thirds of the alpha3(IV)NC1 peptides studied had as
      good or better DR15 affinity than those identified as naturally processed. Thus
      alpha3(IV)NC1 presentation to T cells is determined more by "processing factors"
      than by the preferences of relatively indiscriminate DR15 molecules. The results
      have important implications for the use of class II peptide binding data to aid
      identification of potential T cell epitopes, especially for antigens which, like
      alpha3(IV)NC1, contain many sequences able to bind class II molecules.

PMID- 9565556
TI  - The mutant plasmacytoma cell line S107 allows the identification of distinct
      pathways leading to NF-kappaB activation.
AB  - Studies on the mechanisms of inducible and constitutive activity of NF-kappaB
      transcription factors have been hampered by the lack of appropriate mutant cell
      lines. We have analyzed the defect in the murine S107 plasmacytoma cell line,
      which was previously found to lack both constitutive and inducible NF-kappaB
      activity. Our analysis shows that these cells bear a specific defect that
      interferes with NF-kappaB induction by many diverse stimuli, such as
      lipopolysaccharide, phorbol 12-myristate 13-acetate, UV light, x-rays, and H2O2.
      This does not however represent a general signal transduction defect, because AP
      1 transcription factors are readily induced by the same stimuli. Phosphatase
      inhibitors such as okadaic acid as well as calyculin A can efficiently induce NF
      kappaB in S107 cells via a pathway apparently insensitive to the radical
      scavenger pyrrolidine dithiocarbamate. Furthermore, MEKK1 a protein kinase
      supposedly induced by some of the above stimuli, is also capable of activating NF
      kappaB. Interestingly, both the potent physiological inducer of NF-kappaB
      TNFalpha as well as endoplasmic reticulum overload can induce NF-kappaB via a
      PDTC sensitive pathway. In all cases, DNA-binding NF-kappaB complexes are
      comprised predominantly of p50-RelA heterodimers, and NF-kappaB activation
      results in the induction of transiently transfected or resident reporter genes.
      In summary, these results suggest that the pathways for many NF-kappaB-inducing
      stimuli converge at a specific junction, and this pivotal step is mutated in the
      S107 cell line. Yet there are alternative routes bypassing this critical step
      that also lead to NF-kappaB induction. These routes utilized by tumor necrosis
      factor alpha and endoplasmic reticulum overload are still intact in this cell
      line.

PMID- 9565557
TI  - Alteration of substrate affinities and specificities of the Chlorella Hexose/H+
      symporters by mutations and construction of chimeras.
AB  - The cDNAs HUP1 and HUP2 of Chlorella kessleri code for monosaccharide/H+
      symporters that can be functionally expressed in Schizosaccharomyces pombe. By
      random mutagenesis three HUP1 mutants with an increased Km value for D-glucose
      were isolated. The 40-fold increase in Km of the first mutant is due to the amino
      acid exchange N436I in putative transmembrane helix XI. Two substitutions were
      found in a second (G97C/I303N) and third mutant (G120D/F292L), which show a 270
      fold and 50-fold increase in Km for D-glucose, respectively. An investigation of
      the individual mutations revealed that the substitutions I303N and F292L (both in
      helix VII) cause the Km shifts seen in the corresponding double mutants. These
      mutations together with those previously found support the hypothesis that
      helices V, VII, and XI participate in the transmembrane sugar pathway. Whereas
      for most mutants obtained so far the Km change for D-glucose is paralleled by a
      corresponding change for other hexoses tested, the exchange D44E exclusively
      alters the Km for D-glucose. Moreover the pH profile of this mutant is shifted by
      more than 2 pH units to alkaline values, indicating that the activity of the
      transporter may require deprotonation of the corresponding carboxyl group.
      Chimeric transporters were constructed to study the 100-fold lower affinity for D
      galactose of the HUP1 symporter as compared with that of the HUP2 protein. A
      crucial determinant for the differential D-galactose recognition was shown to be
      associated with the first external loop. The effect could be pinpointed to a
      single amino acid change: replacement of Asn-45 of HUP1 with isoleucine, the
      corresponding amino acid of HUP2, yields a transporter with a 20 times higher
      affinity for D-galactose. The reverse substitution (I47N) decreases the affinity
      of HUP2 for D-galactose 20-fold.

PMID- 9565558
TI  - Mapping of multiple RNA binding sites of human T-cell lymphotropic virus type I
      rex protein within 5'- and 3'-Rex response elements.
AB  - Interaction between the human T-cell lymphotropic virus type I Rex protein and
      viral transcripts in the nucleus is essential to the cytoplasmic appearance of
      unspliced and singly spliced viral RNA. Rex has been shown to mediate its
      function through direct interaction with a highly ordered secondary structure in
      the 3'-untranslated region of all human T-cell lymphotropic virus type I mRNAs
      termed the Rex response element (3'-RxRE). Part of the 3'-RxRE sequence is also
      present in the 5'-end of viral transcripts (5'-RxRE), and we demonstrate that Rex
      binds to this RNA with essentially the same affinity and specificity as to the 3'
      RxRE. We have analyzed the secondary structures and binding sites of Rex within
      the 5'- and 3'-RxREs by enzymatic probing and chemical modification interference
      and show that multiple Rex molecules bind within a stem-loop, which is similarly
      structured in the two RxREs. Our experiments confirm the presence of a previously
      characterized Rex binding site but also identify a common motif within an
      extended region that comprises an additional Rex binding site. This suggests that
      Rex oligomerizes on the RxREs similarly to what has been observed for binding of
      the human immunodeficiency virus type 1 Rev protein to the Rev response element.

PMID- 9565559
TI  - Gonadotropin-releasing hormone receptors with intracellular carboxyl-terminal
      tails undergo acute desensitization of total inositol phosphate production and
      exhibit accelerated internalization kinetics.
AB  - The mammalian gonadotropin-releasing hormone receptor (GnRH-R) is the only G
      protein-coupled receptor (GPCR) in which the intracellular C-terminal tail is
      completely absent. In contrast to other GPCRs, the GnRH-R does not show rapid
      desensitization of total inositol (IP) production, and the rates of
      internalization are exceptionally slow. We investigated whether the incorporation
      of a cytoplasmic tail into the C terminus of the GnRH-R affects desensitization
      events and receptor internalization rates. A GnRH-R/TRH-R chimera was created
      where the intracellular tail of the rat thyrotropin-releasing hormone receptor
      (TRH-R) was engineered into the C terminus of the rat GnRH-R. Three different rat
      GnRH-R cDNA stop codon mutations (one for each reading frame) were also made. The
      GnRH-stimulated IP production of the wild-type rat GnRH-R expressed in either COS
      7 or HEK 293 cells did not desensitize even after prolonged stimulation with
      GnRH. In contrast, the catfish GnRH-R (which does possess an intracellular tail)
      and the TRH-R rapidly (<10 min) desensitized following agonist stimulation. The
      GnRH-R/TRH-R chimera also desensitized following treatment with GnRH, resembling
      the pattern shown by the TRH-R and the catfish GnRH-R. Two of the stop codon
      mutants did not show desensitization of IP production, and the third mutant with
      the longest tail was not functional. Internalization experiments showed that the
      rat GnRH-R had the slowest endocytosis and recycling rates compared with the TRH
      R, the catfish GnRH-R, and the chimeric GnRH/TRH-R. This study demonstrates that
      the addition of a functional intracellular C-terminal tail to the GnRH-R produces
      rapid desensitization of IP production and significantly increases
      internalization rates.

PMID- 9565560
TI  - Chaperone properties of bacterial elongation factor EF-Tu.
AB  - Elongation factor Tu (EF-Tu) is involved in the binding and transport of the
      appropriate codon-specified aminoacyl-tRNA to the aminoacyl site of the ribosome.
      We report herewith that the Escherichia coli EF-Tu interacts with unfolded and
      denatured proteins as do molecular chaperones that are involved in protein
      folding and protein renaturation after stress. EF-Tu promotes the functional
      folding of citrate synthase and alpha-glucosidase after urea denaturation. It
      prevents the aggregation of citrate synthase under heat shock conditions, and it
      forms stable complexes with several unfolded proteins such as reduced
      carboxymethyl alpha-lactalbumin and unfolded bovine pancreatic trypsin inhibitor.
      The EF-Tu.GDP complex is much more active than EF-Tu.GTP in stimulating protein
      renaturation. These chaperone-like functions of EF-Tu occur at concentrations
      that are at least 20-fold lower than the cellular concentration of this factor.
      These results suggest that EF-Tu, in addition to its function in translation
      elongation, might be implicated in protein folding and protection from stress.

PMID- 9565561
TI  - Cell surface glycosaminoglycans do not serve as ligands for PECAM-1. PECAM-1 is
      not a heparin-binding protein.
AB  - Previous studies have suggested that PECAM-1 mediates cellular interactions via
      both homophilic and heterophilic adhesive mechanisms. Cell surface
      glycoaminoglycans have been implicated as one of the heterophilic ligands for
      PECAM-1. To determine whether PECAM-1 is capable of interacting directly with
      glycosaminoglycans, we examined the adhesive properties of multiple monovalent
      and multivalent forms of this adhesion molecule. We found that the binding of a
      bivalent PECAM-1/IgG chimeric protein or multivalent PECAM-1-containing
      proteoliposomes to multiple different cell lines was 1) strictly dependent upon
      cell surface expression of PECAM-1 and 2) unaffected by the presence of excess
      heparin or heparan sulfate. The extracellular domain of PECAM-1 failed to
      interact specifically with heparin-Sepharose, 3H-labeled heparin, or a heparin
      bovine serum albumin conjugate. In addition, an amino acid sequence motif
      inadvertently created by the juxtaposition of PECAM-1 and IgG sequences within
      the hinge region of certain PECAM-1/IgG chimeric constructs was found to confer
      glycosaminoglycan binding properties not normally present within the
      extracellular domain of the native molecule. Together, these data suggest that
      the mechanism by which heparin is able to affect PECAM-1-dependent cell-cell
      adhesion is indirect and occurs via inhibition of events that occur downstream
      from PECAM-1 engagement.

PMID- 9565562
TI  - Pre-steady state of reaction of nucleoside diphosphate kinase with anti-HIV
      nucleotides.
AB  - The pre-steady-state reaction of Dictyostelium nucleoside diphosphate (NDP)
      kinase with dideoxynucleotide triphosphates (ddNTP) and AZT triphosphate was
      studied by quenching of protein fluorescence after manual mixing or by stopped
      flow. The fluorescence signal, which is correlated with the phosphorylation state
      of the catalytic histidine in the enzyme active site, decreases upon ddNTP
      addition according to a monoexponential time course. The pseudo-first order rate
      constant was determined for different concentrations of the various ddNTPs and
      was found to be saturable. The data are compatible with a two-step reaction
      scheme, where fast association of the enzyme with the dideoxynucleotide is
      followed by a rate-limiting phosphorylation step. The rate constants and
      dissociation equilibrium constants determined for each dideoxynucleotide were
      correlated with the steady-state kinetic parameters measured in the enzymatic
      assay in the presence of the two substrates. It is shown that ddNTPs and AZT
      triphosphate are poor substrates for NDP kinase with a rate of phosphate transfer
      of 0.02 to 3.5 s-1 and a KS of 1-5 mM. The equilibrium dissociation constants for
      ADP, GDP, ddADP, and ddGDP were also determined by fluorescence titration of a
      mutant F64W NDP kinase, where the introduction of a tryptophan at the nucleotide
      binding site provides a direct spectroscopic probe. The lack of the 3'-OH in
      ddNTP causes a 10-fold increase in KD. Contrary to "natural" NTPs, NDP kinase
      discriminates between various ddNTPs, with ddGTP the more efficient and ddCTP the
      least efficient substrate within a range of 100 in kcat values.

PMID- 9565563
TI  - pH-induced conformational transitions of the propeptide of human cathepsin L. A
      role for a molten globule state in zymogen activation.
AB  - Synthesis of proteases as inactive zymogens is a very important mechanism for the
      regulation of their activity. For lysosomal proteases proteolytic cleavage of the
      propeptide is triggered by the acidic pH. By using fluorescence, circular
      dichroism, and NMR spectroscopy, we show that upon decreasing the pH from 6.5 to
      3 the propeptide of cathepsin L loses most of the tertiary structure, but almost
      none of the secondary structure is lost. Another partially structured
      intermediate, prone to aggregation, was identified between pH 6.5 and 4. The
      conformation, populated below pH 4, where the activation of cathepsin L occurs,
      is not completely unfolded and has the properties of molten globule, including
      characteristic binding of the 1-anilinonaphthalene-8-sulfonic acid. This pH
      unfolding of the propeptide parallels a decrease of its affinity for cathepsin L
      and suggests the mechanism for the acidic zymogen activation. Addition of anionic
      polysaccharides that activate cathepsin L already at pH 5.5 unfolds the tertiary
      structure of the propeptide at this pH. Propeptide of human cathepsin L which is
      able to fold independently represents an evolutionary intermediate in the
      emergence of novel inhibitors originating from the enzyme proregions.

PMID- 9565564
TI  - Polyomavirus middle T antigen as a probe for T cell antigen receptor-coupled
      signaling pathways.
AB  - Stimulation of the T cell antigen receptor (TCR) triggers a complex series of
      signaling events that culminate in T cell activation and proliferation. The
      complex structure of the TCR has hindered efforts to link specific signaling
      events induced by TCR cross-linkage to downstream activation responses, such as
      interleukin-2 (IL-2) gene transcription. Previous studies have shown that the
      polyomavirus-derived oncoprotein, middle T antigen (mT), transforms rodent
      fibroblasts by interacting with and activating several cytoplasmic signaling
      proteins (Src kinases, phospholipase C (PLC)-gamma1, Shc, and phosphoinositide 3
      kinase (PI3-K) implicated in cell growth control. In this study, we demonstrate
      that expression of mT activates Jurkat T cells, as measured by increases in IL-2
      promoter- and NFAT (nuclear factor of activated T cells)-dependent reporter gene
      transcription. The transcriptional response provoked by mT was blocked by the
      immunosuppressive drug FK506, a potent inhibitor of TCR-mediated IL-2 gene
      expression. Mutations that disrupted the binding of mT to Src kinases or PLC
      gamma1 abrogated the ability of mT to deliver the signals needed for IL-2
      promoter activation. In contrast, a mT mutant that failed to bind PI3-K induced a
      markedly elevated transcriptional response in Jurkat cells, whereas mutation of
      the Shc binding site in mT had little effect on the transactivating potential of
      this viral oncoprotein. Additional studies demonstrated that the association of
      mT with PLC-gamma1 was necessary and sufficient to activate both Ca2+- and Ras
      dependent signaling cascades in Jurkat cells. These results indicate that PLC
      gamma1 activation plays pivotal and pleiotropic roles in the stimulation of IL-2
      gene expression, whereas activation of PI3-K negatively modulates this response
      in Jurkat T cells.

PMID- 9565565
TI  - Phosphatidylglycerol is a physiologic activator of nuclear protein kinase C.
AB  - A major mechanism by which protein kinase C (PKC) function is regulated is
      through the selective targeting and activation of individual PKC isotypes at
      distinct subcellular locations. PKC betaII is selectively activated at the
      nucleus during G2 phase of cell cycle where it is required for entry into
      mitosis. Selective nuclear activation of PKC betaII is conferred by molecular
      determinants within the carboxyl-terminal catalytic domain of the kinase (Walker,
      S. D., Murray, N. R., Burns, D. J., and Fields, A. P. (1995) Proc. Natl. Acad.
      Sci. U. S. A. 92, 9156-9160). We previously described a lipid-like PKC activator
      in nuclear membranes, termed nuclear membrane activation factor (NMAF), that
      potently stimulates PKC betaII activity through interactions involving this
      domain (Murray, N. R., Burns, D. J., and Fields, A. P. (1994) J. Biol. Chem. 269,
      21385-21390). We have now identified NMAF as phosphatidylglycerol (PG), based on
      several lines of evidence. First, NMAF cofractionates with PG as a single peak of
      activity through multiple chromatographic separations and exhibits phospholipase
      sensitivity identical to that of PG. Second, purified PG, but not other
      phospholipids, exhibits dose-dependent NMAF activity. Third, defined molecular
      species of PG exhibit different abilities to stimulate PKC betaII activity. 1,2
      Dioleoyl-PG possesses significantly higher activity than other PG species,
      suggesting that both fatty acid side chain composition and the glycerol head
      group are important determinants for activity. Fourth, in vitro binding studies
      demonstrate that PG binds to the carboxyl-terminal region of PKC betaII, the same
      region we previously implicated in NMAF-mediated activation of PKC betaII. Taken
      together, our results indicate that specific molecular species of nuclear PG
      function to physiologically regulate PKC betaII activity at the nucleus.

PMID- 9565566
TI  - Human protein S cleavage and inactivation by coagulation factor Xa.
AB  - Human factor Xa specifically cleaves the anticoagulant protein S within the
      thrombin-sensitive domain. Amino-terminal amino acid sequencing of the heavy
      chain cleavage product indicates cleavage of protein S by factor Xa at Arg60, a
      site that is distinct from those utilized by alpha-thrombin. Cleavage by factor
      Xa is unaffected by the presence of hirudin and is completely blocked by tick
      anticoagulant-peptide and D-Glu-Gly-Arg-chloromethyl ketone, the latter two being
      specific inhibitors of factor Xa. The cleavage requires the presence of
      phospholipid and Ca2+, and is markedly inhibited by the presence of factor Va.
      Factor Xa-cleaved protein S no longer possesses its activated protein C-dependent
      or -independent anticoagulant activity, as measured in a factor VIII-based
      activated partial thromboplastin time clot assay. The apparent binding constant
      for protein S binding to phospholipid (Kd approximately 4 nM +/- 1.0) is
      unaffected by factor Xa or thrombin cleavage, suggesting that the loss of
      anticoagulant activity resulting from cleavage is not primarily due to the loss
      of membrane binding ability. Cleavage and inactivation of protein S by factor Xa
      may be an additional way in which factor Xa exerts its procoagulant effect, after
      the initial stages of clot formation.

PMID- 9565567
TI  - An import signal in the cytosolic domain of the Neurospora mitochondrial outer
      membrane protein TOM22.
AB  - TOM22 is an integral component of the preprotein translocase of the mitochondrial
      outer membrane (TOM complex). The protein is anchored to the lipid bilayer by a
      central trans-membrane segment, thereby exposing the amino-terminal domain to the
      cytosol and the carboxyl-terminal portion to the intermembrane space. Here, we
      describe the sequence requirements for the targeting and correct insertion of
      Neurospora TOM22 into the outer membrane. The orientation of the protein is not
      influenced by the charges flanking its trans-membrane segment, in contrast to
      observations regarding proteins of other membranes. In vitro import studies
      utilizing TOM22 preproteins harboring deletions or mutations in the cytosolic
      domain revealed that the combination of the trans-membrane segment and
      intermembrane space domain of TOM22 is not sufficient to direct import into the
      outer membrane. In contrast, a short segment of the cytosolic domain was found to
      be essential for the import and assembly of TOM22. This sequence, a novel
      internal import signal for the outer membrane, carries a net positive charge. A
      mutant TOM22 in which the charge of the import signal was altered to -1 was
      imported less efficiently than the wild-type protein. Our data indicate that
      TOM22 contains physically separate import and membrane anchor sequences.

PMID- 9565568
TI  - Simultaneous expression of type 1 and type 2 Lewis blood group antigens by
      Helicobacter pylori lipopolysaccharides. Molecular mimicry between h. pylori
      lipopolysaccharides and human gastric epithelial cell surface glycoforms.
AB  - Previous structural investigations performed on the lipopolysaccharides (LPSs)
      from the human gastric pathogen Helicobacter pylori have revealed that these cell
      surface glycan molecules express type 2 partially fucosylated, glucosylated, or
      galactosylated N-acetyllactosamine O antigen chains (O-chains) of various
      lengths, which may or may not be terminated at the nonreducing end by Lewis X
      (Lex) and/or Ley blood group epitopes in mimicry of human cell surface
      glycoconjugates and glycolipids. Subsequently, serological experiments with
      commercially available Lewis-specific monoclonal antibodies also have recognized
      the presence of Lex and Ley blood group antigens in H. pylori but, in addition,
      have indicated the presence of type 1 chain Lea, Leb, and Led (H-type 1) blood
      group epitopes in some H. pylori strains. To confirm their presence, structural
      studies and additional serological experiments were undertaken on H. pylori
      strains suspected of carrying type 1 chain epitopes. These investigations
      revealed that the O-chain region of H. pylori strain UA948 carried both Lea (type
      1) and Lex (type 2) blood group determinants. The O-chain from H. pylori UA955
      LPS expressed the terminal Lewis disaccharide (type 1 chain) and Lex and Ley
      antigens (type 2). The O-chain of H. pylori J223 LPS carried the type 1 chain
      precursor Lec, the H-1 epitope (Led, type 1 chain) and an elongated
      nonfucosylated type 2 N-acetyllactosamine chain (i antigen). Thus, O-chains from
      H. pylori LPSs can also express fucosylated type 1 sequences, and the LPS from a
      single H. pylori strain may carry O-chains with type 1 and 2 Lewis blood groups
      simultaneously. That monoclonal antibodies putatively specific for the Leb
      determinant can detect glycan substructures (Le disaccharide, Lec, and Led) of
      Leb indicates their nonspecificity. The expression of both type 1 and 2 Lewis
      antigens by H. pylori LPSs mimics the cell surface glycomolecules present in both
      the gastric superficial (which expresses mainly type 1 determinants) and the
      superficial and glandular epithelium regions (both of which express predominantly
      type 2 determinants). Therefore, each H. pylori strain may have a different niche
      within the gastric mucosa, and each individual LPS blood group antigen may have a
      dissimilar role in H. pylori adaptation.

PMID- 9565569
TI  - P2X1 purinoceptor in human platelets. Molecular cloning and functional
      characterization after heterologous expression.
AB  - ADP is an important physiological platelet agonist. The molecular identity of the
      ADP receptor(s) in human platelets, however, is still unclear. Although P2T
      purinoceptor was believed to be the ligand-gated cation channel for ADP in human
      platelets, recent patch clamp studies now suggest it is P2X1 type. In the present
      study, we have cloned a cDNA encoding a P2X1 purinoceptor from human platelets
      using degenerate reverse transcription and polymerase chain reaction. Northern
      blotting with a P2X1-specific probe revealed a band of 1.8 kilobases in human
      platelets as well as in several megakaryoblastic cell lines. 1321N1 human
      astrocytoma cells expressing the cloned P2X1 cDNA exhibited both ATP- and ADP
      stimulated Ca2+ influx that could be blocked by the purinoceptor antagonist
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin. Additionally, a
      polyclonal antibody raised against glutathione-S-transferase-P2X1 fusion peptide
      reacted with a 70-kDa band on Western blot of human platelets. It is therefore
      concluded that functional P2X1 purinoceptors are present in human platelets.

PMID- 9565570
TI  - Dynamics of insulin signaling in 3T3-L1 adipocytes. Differential
      compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and
      IRS-2.
AB  - The ability of the insulin receptor to phosphorylate multiple substrates and
      their subcellular localization are two of the determinants that contribute to
      diversity of signaling. We find that insulin receptor substrate (IRS)-1 is 2-fold
      more concentrated in the intracellular membrane (IM) compartment than in cytosol,
      whereas IRS-2 is 2-fold more concentrated in cytosol than in IM. Insulin
      stimulation induces rapid tyrosine phosphorylation of both IRS-1 and IRS-2. This
      occurs mainly in the IM compartment, even though IRS-2 is located predominantly
      in cytosol. Furthermore, after insulin stimulation, both IRS-1 and IRS-2
      translocate from IM to cytosol with a t1/2 of 3.5 min. Using an in vitro
      reconstitution assay, we have demonstrated an association between IRS-1 and
      internal membranes and have shown that the dissociation of IRS-1 from IM is
      dependent on serine/threonine phosphorylation of IM. By comparison, within 1 min
      after insulin stimulation, 40% of the total pool of the 85-kDa subunit of
      phosphatidylinositol 3-kinase (p85) is recruited from cytosol to IM, the greater
      part of which can be accounted for by binding to IRS-1 present in the IM. The p85
      binding and phosphatidylinositol 3-kinase activity associated with IRS-2 rapidly
      decrease in both IM and cytosol, whereas those associated with IRS-1 stay at a
      relatively high level in IM and increase with time in cytosol despite a return of
      p85 to the cytosol and decreasing tyrosine phosphorylation of cytosolic IRS-1.
      These data indicate that IRS-1 and IRS-2 are differentially distributed in the
      cell and move from IM to cytosol following insulin stimulation. Insulin
      stimulated IRS-1 and IRS-2 signaling occurs mainly in the IM and shows different
      kinetics; IRS-1-mediated signaling is more stable, whereas IRS-2-mediated
      signaling is more transient. These differences in substrate utilization and
      compartmentalization may contribute to the complexity and diversity of the
      insulin signaling network.

PMID- 9565571
TI  - cDNA cloning and expression of bovine UDP-N-acetylglucosamine: alpha1, 3-D
      mannoside beta1,4-N-acetylglucosaminyltransferase IV.
AB  - UDP-N-acetylglucosamine:alpha1,3-D-mannoside beta1, 4-N
      acetylglucosaminyltransferase (GnT-IV) is one of the essential enzymes in the
      production of tri- and tetra-antennary Asn-linked sugar chains. Recently, we have
      successfully purified GnT-IV from bovine small intestine. Based on the partial
      amino acid sequence of the purified bovine GnT-IV enzyme, its cDNA has been
      cloned from bovine small intestine. The open reading frame is 1,605 base pairs
      long, and this sequence produced GnT-IV activity on transient expression in COS-7
      cells. Although the deduced amino acid sequence does not have any significant
      homology with other known N-acetylglucosaminyltransferases (GnTs), the
      hydrophobicity profile showed a typical type II transmembrane protein structure,
      which is common to many glycosyltransferases. N-terminal amino acid sequencing of
      the purified GnT-IV revealed that 92 amino acids, including a transmembrane
      region, were truncated during purification. Of the three potential N
      glycosylation sites Asn-458 was actually glycosylated in the purified enzyme,
      although this N-glycosylation site could be abolished without any reduction in
      GnT-IV activity. Serial deletions at both the N and C termini proved that the
      catalytic domain of GnT-IV is located in the central region of the enzyme. The
      GnT-IV mRNA level correlated with enzymatic activity in the various bovine
      tissues tested.

PMID- 9565572
TI  - Syndecans, heparan sulfate proteoglycans, maintain the proteolytic balance of
      acute wound fluids.
AB  - An imbalance between proteases and antiproteases is thought to play a role in the
      inflammatory injury that regulates wound healing. The activities of some
      proteases and antiproteases found in inflammatory fluids can be modified in vitro
      by heparin, a mast cell-derived glycosaminoglycan. Because syndecans, a family of
      cell surface heparan sulfate proteoglycans, are the major cellular source of
      heparin-like glycosaminoglycan, we asked whether syndecans modify protease
      activities in vivo. Syndecan-1 and syndecan-4 ectodomains are shed into acute
      human dermal wound fluids (Subramanian, S. V., Fitzgerald, M. L., and Bernfield,
      M. (1997) J. Biol. Chem. 272, 14713-14720). Moreover, purified syndecan-1
      ectodomain binds cathepsin G (Kd = 56 nM) and elastase (Kd = 35 nM) tightly and
      reduces the affinity of these proteases for their physiological inhibitors.
      Purified syndecan-1 ectodomain protects cathepsin G from inhibition by alpha1
      antichymotrypsin and squamous cell carcinoma antigen 2 and elastase from
      inhibition by alpha1-proteinase inhibitor by decreasing second order rate
      constants for protease-antiprotease associations (kass) by 3700-, 32-, and 60
      fold, respectively. Both enzymatic degradation of heparan sulfate and
      immunodepletion of the syndecan-1 and -4 in wound fluid reduce these proteolytic
      activities in the fluid, indicating that the proteases in the wound environment
      are regulated by interactions with syndecan ectodomains. Thus, syndecans are shed
      into acute wound fluids, where they can modify the proteolytic balance of the
      fluid. This suggests a novel physiological role for these soluble heparan sulfate
      proteoglycans.

PMID- 9565573
TI  - Analysis of the molecular mechanism of substrate-mediated inactivation of
      leukotriene A4 hydrolase.
AB  - The bifunctional leukotriene A4 hydrolase catalyzes the final step in the
      biosynthesis of the proinflammatory leukotriene B4. During exposure to the
      substrate leukotriene A4, a labile allylic epoxide, the enzyme is gradually
      inactivated as a consequence of the covalent binding of leukotriene A4 to the
      active site. This phenomenon, commonly referred to as suicide inactivation, has
      previously been rationalized as a mechanism-based process in which the enzyme
      converts the substrate to a highly reactive intermediate within an activated
      enzyme-substrate complex that partitions between covalent bond formation
      (inactivation) and catalysis. To further explore the molecular mechanism of the
      self-inactivation of leukotriene A4 hydrolase by leukotriene A4, we prepared and
      analyzed mutated forms of the enzyme that were either catalytically incompetent
      or fully active but resistant toward substrate-mediated inactivation. These
      mutants were treated with leukotriene A4 and leukotriene A4 methyl and ethyl
      esters and subjected to differential peptide mapping and enzyme activity
      determinations, which showed that inactivation and/or covalent modification can
      be completely dissociated from catalysis. Our results, together with recent
      findings described in the literature, argue against a mechanism-based model for
      suicide inactivation. We conclude that the collected data on the substrate
      mediated inactivation of leukotriene A4 hydrolase best conforms to an affinity
      labeling mechanism.

PMID- 9565574
TI  - Fibronectin-mediated cell adhesion is required for induction of 92-kDa type IV
      collagenase/gelatinase (MMP-9) gene expression during macrophage differentiation.
      The signaling role of protein kinase C-beta.
AB  - Induction of the 92-kDa gelatinase (MMP-9) gene expression is associated with
      macrophage differentiation. In this study, we explored the regulatory mechanisms
      underlying this differentiation-associated MMP-9 gene expression in human HL-60
      myeloid leukemia cells and human peripheral blood monocytes. Phorbol 12-myristate
      13-acetate (PMA) markedly induced MMP-9 gene expression in HL-60 cells; the
      induction closely paralleled the timing and extent of PMA-induced cell adhesion
      and spreading, a hallmark of macrophage differentiation. Similarly, treatment
      with PMA or macrophage-colony stimulating factor stimulated adherence and
      spreading of blood monocytes with a concurrent 7- or 5-fold increase in MMP-9
      production, respectively. In protein kinase C (PKC)-beta-deficient HL-60 variant
      cells (HL-525), PMA failed to induce cell adhesion and MMP-9 gene expression.
      Transfecting HL-525 cells with a PKC-beta expression plasmid restored PKC-beta
      levels and PMA inducibility of cell adhesion and spreading as well as MMP-9 gene
      expression. Induction of cell adhesion and MMP-9 gene expression in HL-60 cells
      and blood monocytes was strongly inhibited by neutralizing monoclonal antibodies
      to fibronectin (FN) and its receptor alpha5 beta1 integrin. HL-525 cells, which
      constitutively display high levels of surface alpha5 beta1 integrin, adhered and
      spread on immobilized FN with concomitant induction of MMP-9 gene expression.
      Cytochalasins B and D were each a potent inhibitor of MMP-9 production. Our
      results suggest that alpha5 beta1 integrin-mediated interaction of immature
      hematopoietic cells with FN plays a critical role in modulating matrix-degrading
      activities during macrophage differentiation.

PMID- 9565575
TI  - Autocrine regulation of macrophage differentiation and 92-kDa gelatinase
      production by tumor necrosis factor-alpha via alpha5 beta1 integrin in HL-60
      cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) gene is one of the early response genes
      induced by phorbol 12-myristate 13-acetate (PMA) in human HL-60 myeloid leukemia
      cells. In the present study, we examined the role of the TNF-alpha autocrine loop
      in PMA-induced macrophage differentiation and gene expression of 92- and 72-kDa
      gelatinases (MMP-9 and MMP-2). In HL-60 cells, PMA inhibited cell proliferation
      and induced cell adhesion and spreading, expression of surface maturation marker
      OKM1 and phagocytic activity, as well as the expression of both gelatinases,
      which all characterize the macrophage phenotype. In contrast, TNF-alpha alone was
      only effective in inhibiting cell proliferation. Blocking the endogenous TNF
      alpha activity with neutralizing anti-TNF-alpha antibodies abolished all these
      PMA-induced events with the exception of MMP-2 gene expression. Since fibronectin
      (FN)-mediated cell adhesion and spreading are prerequisite for both macrophage
      differentiation and MMP-9 gene expression in HL-60 cells, we hypothesized that
      TNF-alpha might be involved in modulating the expression of either the FN or its
      integrin receptor genes. Whereas PMA substantially enhanced the steady state mRNA
      and protein levels of both FN and alpha5 beta1 integrins, TNF-alpha alone had
      little effect on the expression of these genes. However, anti-TNF-alpha
      antibodies blocked PMA-induced augmentation of both alpha5 and beta1 integrin
      gene expression without affecting the expression of the FN gene. Our results
      suggest that TNF-alpha may regulate macrophage differentiation and critical
      matrix-degrading activities of myeloid progenitor cells in an autocrine manner by
      augmenting surface levels of the alpha5 beta1 integrin, thus promoting
      interactions with the extracellular matrix, a key event for maturation and
      migration of these cells during inflammation.

PMID- 9565576
TI  - A catalytic domain of eukaryotic DNA topoisomerase I.
AB  - Eukaryotic type IB topoisomerases catalyze the cleavage and rejoining of DNA
      strands through a DNA-(3'-phosphotyrosyl)-enzyme intermediate. The 314-amino acid
      vaccinia topoisomerase is the smallest member of this family and is distinguished
      from its cellular counterparts by its specificity for cleavage at the target
      sequence 5'-CCCTT downward arrow. Here we show that Topo-(81-314), a truncated
      derivative that lacks the N-terminal domain, performs the same repertoire of
      reactions as the full-sized topoisomerase: relaxation of supercoiled DNA, site
      specific DNA transesterification, and DNA strand transfer. Elimination of the N
      terminal domain slows the rate of single-turnover DNA cleavage by 10(-3.6), but
      has little effect on the rate of single-turnover DNA religation. DNA relaxation
      and strand cleavage by Topo-(81-314) are inhibited by salt and magnesium; these
      effects are indicative of reduced affinity in noncovalent DNA binding. We report
      that identical properties are displayed by a full-length mutant protein,
      Topo(Y70A/Y72A), which lacks two tyrosine side chains within the N-terminal
      domain that contact the DNA target site in the major groove. We speculate that
      Topo-(81-314) is fully competent for transesterification chemistry, but is
      compromised with respect to a rate-limiting precleavage conformational step that
      is contingent on DNA contacts made by Tyr-70 and Tyr-72.

PMID- 9565577
TI  - Determination of interaction sites on the small G protein RhoA for phospholipase
      D.
AB  - Phospholipase D (PLD) has been identified as a target of small G proteins of the
      Rho family. The present study was directed at defining the interaction sites of
      RhoA with rat brain PLD in vitro using chimeric proteins between RhoA and Ha-Ras
      or Cdc42Hs and point mutations. The switch I region of RhoA, which is the common
      effector domain of Ras-like G proteins, was a crucial interaction site for PLD.
      Mutations in conserved amino acids (Tyr34, Thr37, Phe39) totally abolished PLD
      activation, while mutations in Val38 or Tyr42 caused partial loss. Two additional
      sites were responsible for the differential PLD activation ability between RhoA
      and Cdc42Hs. Changing Asp76 in the switch II region of RhoA to the corresponding
      amino acid in Cdc42Hs led to partial loss of PLD activation. A chimeric protein
      with the N-terminal third of Cdc42Hs changed to RhoA showed enhanced PLD
      activation. Analysis of other Rho/Ha-Ras chimeric proteins and mutations
      indicated that Gln52 adjacent to the switch II region is responsible for this
      gain of function. In conclusion, the present study shows that conserved amino
      acids in the switch I region of RhoA are major PLD interaction sites and that
      residues in the switch II and internal regions are responsible for the
      differential activation of PLD by RhoA and Cdc42Hs.

PMID- 9565578
TI  - Sequences outside recognition sets are not neutral for tRNA aminoacylation.
      Evidence for nonpermissive combinations of nucleotides in the acceptor stem of
      yeast tRNAPhe.
AB  - Phenylalanine identity of yeast tRNAPhe is governed by five nucleotides including
      residues A73, G20, and the three anticodon nucleotides (Sampson et al., 1989,
      Science 243, 1363-1366). Analysis of in vitro transcripts derived from yeast
      tRNAPhe and Escherichia coli tRNAAla bearing these recognition elements shows
      that phenylalanyl-tRNA synthetase is sensitive to additional nucleotides within
      the acceptor stem. Insertion of G2-C71 has dramatic negative effects in both tRNA
      frameworks. These effects become compensated by a second-site mutation, the
      insertion of the wobble G3-U70 pair, which by itself has no effect on
      phenylalanylation. From a mechanistic point of view, the G2-C71/G3-U70
      combination is not a "classical" recognition element since its antideterminant
      effect is compensated for by a second-site mutation. This enlarges our
      understanding of tRNA identity that appears not only to be the outcome of a
      combination of positive and negative signals forming the so-called
      recognition/identity set but that is also based on the presence of nonrandom
      combinations of sequences elsewhere in tRNA. These sequences, we name "permissive
      elements," are retained by evolution so that they do not hinder aminoacylation.
      Likely, no nucleotide within a tRNA is of random nature but has been selected so
      that a tRNA can fulfill all its functions efficiently.

PMID- 9565579
TI  - Isolation and characterization of thymitaq (AG337) and 5-fluoro-2-deoxyuridylate
      resistant mutants of human thymidylate synthase from ethyl methanesulfonate
      exposed human sarcoma HT1080 cells.
AB  - Thymidylate synthase plays an essential role in the synthesis of DNA. Recently,
      several new and specific thymidylate synthase inhibitors that occupy the folate
      binding site, including Tomudex(R), BW1843U89, and Thymitaq, have demonstrated
      therapeutic activity in patients with advanced cancer. In order to find drug
      resistant forms of human thymidylate synthase for gene therapy applications,
      human sarcoma HT1080 cells were exposed to ethyl methanesulfonate and Thymitaq
      selection. Thymitaq-resistant clonal derived sublines were established, and
      analysis indicated that both gene amplification and point mutations contributed
      to drug resistance. Eight mutant cDNAs that were identified from Thymitaq
      resistant sublines were generated by site-directed mutagenesis and transfected
      into thymidylate synthase-negative cells. Only K47E, D49G, or G52S mutants retain
      enzyme activity. Moreover, cytotoxicity studies demonstrated that D49G and G52S
      transfected cells, besides displaying resistance to Thymitaq with IC50 values 40-
      and 12-fold greater than wild-type enzyme transfected cells, respectively, also
      lead to fluorodeoxyuridine resistance (26- and 97-fold in IC50 values,
      respectively) but not to Tomudex or BW1843U89. Characterization of the purified
      altered enzymes obtained from expression in Escherichia coli is consistent with
      the cell growth inhibition results. We postulate that the D49G or G52S mutation
      leads to the structural perturbation of the highly conserved Arg50 loop,
      decreasing the binding of thymidylate synthase to the inhibitors, Thymitaq and
      fluorodeoxyuridylate.

PMID- 9565581
TI  - Folding of chromatin in the presence of heterogeneous histone H1 binding to
      nucleosomes.
AB  - We have reconstituted oligonucleosome complexes containing histone H1 starting
      from a synthetic DNA template, consisting of 12 tandemly arranged 208-base pair
      fragments of the 5 S rRNA gene, purified HeLa histone octamers, and histone H1. A
      ratio of histone H1 per histone octamer used in the reconstitution (0.8-0.9 mol
      of histone H1/mol of histone octamer) similar to that observed in vivo was used.
      The reconstituted chromatin complexes exhibit a salt-dependent folding, which is
      almost indistinguishable from that exhibited by chromatin fragments obtained from
      nuclease digestion of native chromatin. The folding of this reconstituted
      chromatin complex seems to be rather independent of the symmetrical or
      asymmetrical position occupied by H1 in the individual nucleosomes. Binding of
      histone H1 to the oligonucleosome complexes, under the stoichiometric binding
      conditions used, had no inhibitory effect on the transcriptional potential of
      these complexes.

PMID- 9565580
TI  - Intracellular signaling by reactive oxygen species during hypoxia in
      cardiomyocytes.
AB  - Cardiomyocytes suppress contraction and O2 consumption during hypoxia. Cytochrome
      oxidase undergoes a decrease in Vmax during hypoxia, which could alter
      mitochondrial redox and increase generation of reactive oxygen species (ROS). We
      therefore tested whether ROS generated by mitochondria act as second messengers
      in the signaling pathway linking the detection of O2 with the functional
      response. Contracting cardiomyocytes were superfused under controlled O2
      conditions while fluorescence imaging of 2, 7-dichlorofluorescein (DCF) was used
      to assess ROS generation. Compared with normoxia (PO2 approximately 107 torr, 15%
      O2), graded increases in DCF fluorescence were seen during hypoxia, with
      responses at PO2 = 7 torr > 20 torr > 35 torr. The antioxidants 2
      mercaptopropionyl glycine and 1,10-phenanthroline attenuated these increases and
      abolished the inhibition of contraction. Superfusion of normoxic cells with H2O2
      (25 microM) for >60 min mimicked the effects of hypoxia by eliciting decreases in
      contraction that were reversible after washout of H2O2. To test the role of
      cytochrome oxidase, sodium azide (0.75-2 microM) was added during normoxia to
      reduce the Vmax of the enzyme. Azide produced graded increases in ROS signaling,
      accompanied by graded decreases in contraction that were reversible. These
      results demonstrate that mitochondria respond to graded hypoxia by increasing the
      generation of ROS and suggest that cytochrome oxidase may contribute to this O2
      sensing.

PMID- 9565582
TI  - Biphasic activation of PKBalpha/Akt in platelets. Evidence for stimulation both
      by phosphatidylinositol 3,4-bisphosphate, produced via a novel pathway, and by
      phosphatidylinositol 3,4,5-trisphosphate.
AB  - Stimulation of platelet thrombin receptors or protein kinase C causes fibrinogen
      dependent aggregation that is a function of integrin alphaIIb beta3 activation.
      Such platelets rapidly and transiently form phosphatidylinositol 3,4,5
      trisphosphate (PtdIns(3,4,5)P3) and a small amount of phosphatidylinositol 3,4
      bisphosphate (PtdIns(3,4)P2). After aggregation, a larger amount of PtdIns(3,4)P2
      is generated. We report that this latter PtdIns(3,4)P2 arises largely through
      wortmannin-inhibitable generation of PtdIns3P and then phosphorylation by
      PtdIns3P 4-kinase (PtdIns3P 4-K), a novel pathway apparently contingent upon the
      activation of the Ca2+-dependent protease calpain. Elevation of cytosolic Ca2+ by
      ionophore, without integrin/ligand binding, is insufficient to activate the
      pathway. PtdIns3P 4-K is not the recently described "PIP5KIIalpha." Cytoskeletal
      activities of phosphatidylinositol 3-kinase and PtdIns3P 4-K increase after
      aggregation. Prior to aggregation, PtdIns3P 4-K can be regulated negatively by
      the beta gamma subunit of heterotrimeric GTP-binding protein. After aggregation,
      PtdIns3P 4-K calpain-dependently loses its susceptibility to Gbeta gamma and is,
      in addition, activated. Both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 have been shown to
      stimulate PKBalpha/Akt phosphorylation and activation by phosphoinositide
      dependent kinase 1. We find that activation of PKBalpha/Akt in platelets is
      phosphorylation-dependent and biphasic; the initial phase is PtdIns(3,4,5)P3
      dependent and more efficient, whereas the second phase depends upon PtdIns(3,4)P2
      generated after aggregation. There is thus potential for both pre- and post
      aggregation-dependent signaling by PKBalpha/Akt.

PMID- 9565583
TI  - Regulation of phosphatidylglycerophosphate synthase levels in Saccharomyces
      cerevisiae.
AB  - The PGS1 gene of Saccharomyces cerevisiae encodes phosphatidylglycerophosphate
      (PG-P) synthase. PG-P synthase activity is regulated by factors affecting
      mitochondrial development and through cross-pathway control by inositol. The
      molecular mechanism of this regulation was examined by using a reporter gene
      under control of the PGS1 gene promoter (PPGS1-lacZ). Gene expression subject to
      carbon source regulation was monitored both at steady-state level and during the
      switch between different carbon sources. Cells grown in a non-fermentable carbon
      source had beta-galactosidase levels 3-fold higher than those grown in glucose. A
      shift from glucose to lactate rapidly raised the level of gene expression,
      whereas a shift back to glucose had the opposite effect. In either a pgs1 null
      mutant or a rho mutant grown in glucose, PPGS1-lacZ expression was 30-50% of the
      level in wild type cells. Addition of inositol to the growth medium resulted in a
      2-3-fold reduction in gene expression in wild type cells. In ino2 and ino4
      mutants, gene expression was greatly reduced and was not subject to inositol
      regulation consistent with inositol repression being dependent on the INO2 and
      INO4 regulatory genes. PPGS1-lacZ expression was elevated in a cds1 null mutant
      in the presence or absence of inositol, indicating that the capacity to
      synthesize CDP-diacylglycerol affects gene expression. Lack of cardiolipin
      synthesis (cls1 null mutant) had no effect on reporter gene expression.

PMID- 9565584
TI  - An alternative domain determines nuclear localization in multifunctional protein
      4.1.
AB  - Multiple protein 4.1 isoforms are originated by alternative pre-mRNA splicing,
      differential use of two translation initiation sites, and posttranslational
      modifications. The complexity of alternative splicing events suffered by the 4.1
      pre-mRNA makes necessary the direct cloning of 4.1 full-coding cDNA sequences to
      ensure that the encoded 4.1 proteins are naturally occurring isoforms. We have
      approached this point by reverse transcription-polymerase chain reaction
      techniques using RNA from the nucleated human Molt-4 T-cell line as a starting
      template. Molecular cloning of 4.1 cDNAs using the second translation initiation
      codon has allowed us to identify two 4.1 isoforms, designated 4.1H and 4.1I,
      which are differentially targeted to the nucleus (4.1H) and the cytoplasm (4.1I).
      These two isoforms differ only in the inclusion (4.1H) or exclusion (4.1I) of 21
      amino acids encoded by exon 16. A cluster of basic amino acids, KKKR, generated
      by joining of the sequences encoded by the constitutive exon 13 and the
      alternative exon 16, is necessary for the nuclear targeting of 4.1H, as
      demonstrated by site-directed mutagenesis analysis. Immunofluorescence microscopy
      and biochemical studies indicate that 4.1H belongs to the group of nuclear 4.1
      proteins that are distributed diffusely throughout the nucleoplasm and that are
      extractable in 0.5% Triton X-100. This is the first demonstration of differential
      nuclear targeting by the presence of an alternative domain, among naturally
      occurring protein 4.1 isoforms.

PMID- 9565585
TI  - Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational
      analysis of residues within the active site and hydrophobic ridge of plcdelta1.
AB  - Structural studies of phospholipase C delta1 (PLCdelta1) in complexes with the
      inositol-lipid headgroup and calcium identified residues within the catalytic
      domain that could be involved in substrate recognition, calcium binding, and
      catalysis. In addition, the structure of the PLCdelta1 catalytic domain revealed
      a cluster of hydrophobic residues at the rim of the active site opening
      (hydrophobic ridge). To assess a role of each of these residues, we have
      expressed, purified, and characterized enzymes with the point mutations of
      putative active site residues (His311, Asn312, Glu341, Asp343, His356, Glu390,
      Lys438, Lys440, Ser522, Arg549, and Tyr551) and residues from the hydrophobic
      ridge (Leu320, Phe360, and Trp555). The replacements of most active site residues
      by alanine resulted in a great reduction (1,000-200,000-fold) of PLC activity
      analyzed in an inositol lipid/sodium cholate mixed micelle assay. Measurements of
      the enzyme activity toward phosphatidylinositol, phosphatidylinositol 4
      monophosphate, and phosphatidylinositol 4, 5-bis-phosphate (PIP2) identified
      Ser522, Lys438, and Arg549 as important for preferential hydrolysis of
      polyphosphoinositides, whereas replacement of Lys440 selectively affected only
      hydrolysis of PIP2. When PLC activity was analyzed at different calcium
      concentrations, substitutions of Asn312, Glu390, Glu341, and Asp343 resulted in a
      shift toward higher calcium concentrations required for PIP2 hydrolysis,
      suggesting that all these residues contribute toward Ca2+ binding. Mutational
      analysis also confirmed the importance of His311 ( approximately 20,000-fold
      reduction) and His356 ( approximately 6,000-fold reduction) for the catalysis.
      Mutations within the hydrophobic ridge, which had little effect on PIP2
      hydrolysis in the mixed-micelles, resulted in an enzyme that was less dependent
      on the surface pressure when analyzed in a monolayer. This systematic mutational
      analysis provides further insights into the structural basis for the substrate
      specificity, requirement for Ca2+ ion, catalysis, and surface pressure/activity
      dependence, with general implications for eukaryotic phosphoinositide-specific
      PLCs.

PMID- 9565586
TI  - BAG-1L protein enhances androgen receptor function.
AB  - BAG-1 is a regulator of heat shock protein (Hsp) 70/Hsc70 family proteins that
      interacts with steroid hormone receptors. The recently identified BAG-1 long (BAG
      1L) protein, an isoform of BAG-1 that arises from translation initiation at a
      noncanonical CUG codon, was co-immunoprecipitated with androgen receptors (AR)
      from LNCaP prostate cancer cells and other cell lysates, whereas the shorter
      originally identified BAG-1 and BAG-1M (RAP 46) proteins were not. BAG-1L, but
      not BAG-1 or BAG-1M (RAP46), also markedly enhanced the ability of AR to
      transactivate reporter gene plasmids containing an androgen response element
      (ARE) in PC3 prostate cancer and other cell lines. A C-terminal region deletion
      mutant of BAG-1L failed to co-immunoprecipitate with AR and functioned as a trans
      dominant inhibitor of BAG-1L, impairing AR-induced transactivation of ARE
      containing reporter plasmids. In addition, BAG-1L significantly reduced the
      concentrations of 5alpha-dihydrotestosterone (DHT) required for AR activity but
      did not induce ligand-independent transactivation. BAG-1L also markedly improved
      the ability of AR to transactivate reporter genes when cells were cultured with
      DHT in combination with the anti-androgen cyproterone acetate. The effects of BAG
      1L on AR could not be explained by detectable alterations in the DHT-induced
      translocation of AR from cytosol to nucleus, nor by BAG-1L-induced increases in
      the amounts of AR protein. These findings implicate BAG-1L in the regulation of
      AR function and may have relevance to mechanisms of prostate cancer resistance to
      hormone-ablative and anti-androgen therapy.

PMID- 9565587
TI  - Binding interaction of the heregulinbeta egf domain with ErbB3 and ErbB4
      receptors assessed by alanine scanning mutagenesis.
AB  - Individual residues of the heregulinbeta (HRG) egf domain were mutated to alanine
      and displayed monovalently on phagemid particles as gene III fusion proteins.
      Wild type HRGbeta egf domain displayed on phage was properly folded as evidenced
      by its ability to bind ErbB3 and ErbB4 receptor-IgG fusion proteins with
      affinities close to those measured for bacterially produced HRGbeta egf domain.
      Binding to ErbB3 and ErbB4 receptors was affected by mutation of residues
      throughout the egf domain; including the NH2 terminus (His2 and Leu3), the two
      beta-turns (Val15-Gly18 and Gly42-Gln46), and some discontinuous residues
      (including Leu3, Val4, Phe13, Val23, and Leu33) that form a patch on the major
      beta-sheet and the COOH-terminal region (Tyr48 and Met50-Phe53). Binding affinity
      was least changed by mutations throughout the Omega-loop and the second strand of
      the major beta-sheet. More mutants had greater affinity loss for ErbB3 compared
      with ErbB4 implying that it has more stringent binding requirements. Many
      residues important for HRG binding to its receptors correspond to critical
      residues for epidermal growth factor (EGF) and transforming growth factor alpha
      binding to the EGF receptor. Specificity may be determined in part by bulky
      groups that prevent binding to the unwanted receptor. All of the mutants tested
      were able to induce phosphorylation and mitogen-activated protein kinase
      activation through ErbB4 receptors and were able to modulate a
      transphosphorylation signal from ErbB3 to ErbB2 in MCF7 cells. An understanding
      of binding similarities and differences among the EGF family of ligands may
      facilitate the development of egf-like analogs with broad or narrow specificity.

PMID- 9565588
TI  - Selection of heregulin variants having higher affinity for the ErbB3 receptor by
      monovalent phage display.
AB  - Heregulins (HRGs) are epidermal growth factor (egf) domain containing polypeptide
      growth factors that bind and activate several members of the ErbB receptor
      family. Although HRG can bind to ErbB3 and ErbB4 homodimers, the highest affinity
      and most intracellularly active receptor complexes are hetero-oligomers
      containing ErbB2. The HRGbeta egf domain was displayed on the surface of M13
      phage to facilitate mutagenic analysis and optimize for binding to a homodimeric
      ErbB3-immunoglobulin (IgG) fusion. Nine libraries were constructed in which
      virtually the entire sequence was randomized in stretches of four to six amino
      acids. These were selected separately for binding to immobilized ErbB3-IgG.
      Analysis of the resulting sequences revealed some areas that diverged radically
      from the wild-type, whereas others showed strong conservation. The degree of wild
      type conservation correlated strongly with the functional importance of the
      residues as determined by alanine scanning mutagenesis (Jones, J. T., Ballinger,
      M. D., Pisacane, P. I., Lofgren, J. A., Fitzpatrick, V. D., Fairbrother, W. J.,
      Wells, J. A., and Sliwkowski, M. X. (1998) J. Biol. Chem. 273, 11667-11674). Some
      variants from several libraries showed significant improvements in binding
      affinity to the ErbB3-IgG. These optimized segments were combined in various ways
      in the same molecule to generate variants (containing up to 16 mutations) that
      had >50-fold higher affinity than wild-type HRGbeta. The optimized variants
      stimulated ErbB2 phophorylation on MCF7 cells at levels similar to wild-type.
      This indicates wild-type affinity is optimized for potency and that factors other
      than affinity for ErbB3 are limiting. These variants showed enhanced affinity
      toward the ErbB4 homodimer, suggesting these receptors use very similar binding
      determinants despite them having 65% sequence identity.

PMID- 9565589
TI  - Identification of amino acid residues of Gsalpha critical to repression of
      adipogenesis.
AB  - Gsalpha regulates the differentiation of 3T3-L1 mouse embryonic fibroblasts to
      adipocytes, a process termed adipogenesis. Through the expression of chimera
      created by substituting regions of Gsalpha with corresponding regions of the G
      protein Gialpha2, the domain of Gsalpha involved in repression of adipogenesis
      was localized to sequence 146-235 of the molecule (Wang, H-y., Johnson, G. L.,
      Liu, X. , Malbon, C. C. (1996) J. Biol. Chem. 271, 22022-22029). As a prelude to
      alanine-scanning mutagenesis, chimeras in Gsalpha constructed from trisection of
      the sequence 125-213 of Gialpha2 were expressed stably, and clones were evaluated
      for the ability of the chimera to repress adipogenesis in response to the
      inducers, dexamethasone and methylisobutylxanthine, in combination. The chimera
      containing sequence 150-177 of Gialpha2 repressed adipogenesis, whereas the
      chimeras with either sequence 125-149 or 178-213 of Gialpha2 failed to repress
      induction of adipogenesis. Alanine-scanning mutagenesis of these two critical
      domains was performed first in clusters and then confirmed by analysis of single
      mutations. Six residues unique to Gsalpha were identified as critical to
      repression of adipogenesis, Asn167, Cys200, Leu203, Ser205, Val214, and Lys216.
      Leu203 and Ser205 are required in tandem, as mutagenesis to alanine of either one
      alone was without effect on repressor activity. The remaining four residues are
      required for repressor activity; mutation of any one of these abolishes the
      ability of Gsalpha to repress adipogenesis, although not affecting the ability of
      the mutant form of Gsalpha to regulate adenylylcyclase. Using conserved landmarks
      found in the crystal structures of Gialpha1 and Gsalpha, the Leu203 and Ser205
      cluster appears to be exposed, closely aligned and located in switch I region.
      Asn167, Val214, and Lys216 project to regions on Gsalpha that are exposed in the
      GTPgammaS-liganded state of the alpha subunit. We speculate that these residues
      constitute an important contact domain between Gsalpha and the effector
      controlling adipogenesis, which is yet to be identified.

PMID- 9565590
TI  - Natriuretic peptide regulation of endochondral ossification. Evidence for
      possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.
AB  - The natriuretic peptide family consists of three structurally related endogenous
      ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C
      type natriuretic peptide (CNP). The biological actions of natriuretic peptides
      are thought to be mediated through the activation of two guanylyl cyclase (GC)
      coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects
      of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on
      bone growth using an organ culture of fetal mouse tibias, an in vitro model of
      endochondral ossification. CNP increased the cGMP production much more potently
      than ANP, thereby resulting in an increase in the total longitudinal bone length.
      Histological examination revealed an increase in the height of the proliferative
      and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The
      natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo
      cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide
      receptor antagonist. The spontaneous increase in the total longitudinal bone
      growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA
      was expressed abundantly in fetal mouse tibias, where no significant amounts of
      ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present
      in fetal mouse tibias. This study suggests the physiologic significance of the
      CNP/GC-B pathway in the process of endochondral ossification.

PMID- 9565591
TI  - Hyperactivity of human DNase I variants. Dependence on the number of positively
      charged residues and concentration, length, and environment of DNA.
AB  - Human DNase I, an enzyme used to treat cystic fibrosis patients, has been
      engineered to more effectively degrade double-stranded DNA to lower molecular
      weight forms by introducing positively charged amino acids at positions that can
      interact favorably with the proximal negatively charged phosphate groups of the
      DNA. A series of combination mutants having from one to six additional basic
      residues compared with the wild type has been constructed, expressed in human 293
      cells, and characterized. The degree of hyperactivity for the mutants was highly
      dependent upon the conditions in various assays, including the concentration and
      length of the DNA substrate and the salt and divalent metal ion concentrations.
      The level of hyperactivity was inversely proportional to both DNA concentration
      and DNA length, consistent with the processive nicking mechanism for the
      hyperactive variants. Salt was inhibitory for wild type DNase I but actually
      enhanced the activity of the hyperactive variants. Under optimal conditions for
      wild type, variants with one additional positive charge possessed the highest
      activity, which was only severalfold greater than that for wild type. However, in
      the presence of low DNA concentrations and molecular weights, no Ca2+, and 150 mM
      NaCl, the variant with six engineered basic residues was most active, having
      >10,000-fold higher activity than the wild type enzyme. Therefore, any potential
      increase in potency for the hyperactive variants in vivo will be determined by
      the concentration, length, and environment of the DNA.

PMID- 9565592
TI  - Leupaxin is a novel LIM domain protein that forms a complex with PYK2.
AB  - We have identified a novel cytoplasmic protein, leupaxin, that is preferentially
      expressed in hematopoietic cells and is most homologous to the focal adhesion
      protein, paxillin. Leupaxin possesses two types of protein interaction domains.
      There are four carboxyl-terminal LIM domains in leupaxin that share 70% amino
      acid identity and 80% similarity with those in paxillin. Paxillin LIM domains
      mediate localization to focal contacts. In the amino-terminal region of leupaxin
      there are three short stretches of approximately 13 amino acids that share 70-90%
      similarity with paxillin LD motifs. Paxillin LD motifs have been implicated in
      focal adhesion kinase (FAK) and vinculin binding resulting in the localization of
      FAK to focal adhesions. Leupaxin is expressed in cell types, such as macrophage,
      that lack FAK. We demonstrate here that leupaxin associates with a second FAK
      family member, PYK2. As leupaxin and PYK2 are both preferentially expressed in
      leukocytes they may therefore form a cell type-specific signaling complex. We
      also demonstrate that leupaxin is a substrate for a tyrosine kinase in lymphoid
      cells and thus may function in and be regulated by tyrosine kinase activity.
      Leupaxin is thus a phosphotyrosine protein with LD and LIM binding motifs most
      homologous to paxillin that may assemble and regulate PYK2 signaling complexes in
      leukocytes.

PMID- 9565593
TI  - Binding of an oligopeptide to a specific plane of ice.
AB  - The alpha-helical antifreeze protein (AFP) from winter flounder inhibits ice
      growth by binding to a specific set of pyramidal surface planes that are not
      otherwise macroscopically expressed. The 37-residue AFP contains three 11-amino
      acid repeats that make a stereo-specific fit to the ice lattice along the <01-12>
      direction of the (20-21) and equivalent binding planes. When the AFP was
      shortened to delete two of the three 11-amino acid ice-binding repeats, the
      resulting 15-residue peptide and its variants were less helical and showed no
      antifreeze activity. However, when the helicity of the peptide was reinforced by
      an internal lactam bridge between Glu-7 and Lys-11, the minimized AFP was able to
      stably express the pyramidal plane (20-21) on the surface of growing ice
      crystals. This dynamic shaping of the ice surface by a single ice-binding repeat
      provides evidence that AFP adsorption to the ice lattice is not an "all-or
      nothing" interaction. Instead, a partial interaction can help develop the binding
      site on ice to which the remainder of the AFP (or other AFP molecules) can orient
      and bind.

PMID- 9565595
TI  - Phosphorylation of vimentin by Rho-associated kinase at a unique amino-terminal
      site that is specifically phosphorylated during cytokinesis.
AB  - We found that vimentin, the most widely expressed intermediate filament protein,
      served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that
      vimentin phosphorylated by Rho-kinase lost its ability to form filaments in
      vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as
      the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored
      and unique phosphorylation site for Rho-kinase in vitro. To analyze the vimentin
      phosphorylation by Rho-kinase in vivo, we prepared an antibody GK71 that
      specifically recognizes the phosphorylation of vimentin-Ser71. Ectopic expression
      of constitutively active Rho-kinase in COS-7 cells induced phosphorylation of
      vimentin at Ser71, followed by the reorganization of vimentin filament networks.
      During the cell cycle, the phosphorylation of vimentin-Ser71 occurred only at the
      cleavage furrow in late mitotic cells but not in interphase or early mitotic
      cells. This cleavage furrow-specific phosphorylation of vimentin-Ser71 was
      observed in the various types of cells we examined. All these accumulating
      observations increase the possibility that Rho-kinase may have a definite role in
      governing regulatory processes in assembly-disassembly and turnover of vimentin
      filaments at the cleavage furrow during cytokinesis.

PMID- 9565594
TI  - Tlg2p, a yeast syntaxin homolog that resides on the Golgi and endocytic
      structures.
AB  - Intracellular membrane fusion events in eukaryotic cells are thought to be
      mediated by protein-protein interactions between soluble N-ethylmaleimide
      sensitive factor attachment protein receptor (SNARE) complex proteins. We have
      identified and analyzed a new yeast syntaxin homolog, Tlg2p. Tlg2p is unique
      among known syntaxin family proteins in possessing a sizeable hydrophilic domain
      of 63 amino acids that is C-terminal to the membrane spanning region and
      nonessential for Tlg2p function. Tlg2p resides on the endosome and late Golgi by
      co-localization with an endocytic intermediate and co-fractionation with markers
      for both endosomes and late Golgi. Cells depleted for Tlg2p missort a portion of
      carboxypeptidase Y and are defective in endocytosis. In addition, we report that
      Tlg2p forms a SEC18-dependent SNARE complex with Snc2p, a vesicle SNARE known to
      function in Golgi to plasma membrane trafficking. Based on these findings we
      propose that Tlg2p is a t-SNARE that functions in transport from the endosome to
      the late Golgi and on the endocytic pathway.

PMID- 9565596
TI  - The human ICAM-2 promoter is endothelial cell-specific in vitro and in vivo and
      contains critical Sp1 and GATA binding sites.
AB  - The expression of intercellular adhesion molecule 2 (ICAM-2) in adult tissues is
      restricted to vascular endothelial cells and megakaryocytes. We have previously
      shown that the endothelial-specific in vivo activity of the human ICAM-2 promoter
      is contained within a small (0.33-kilobase (kbp)) 5'-flanking region of the gene.
      Here we describe the in vitro characterization of this region. The ICAM-2
      promoter is TATA-less, and transcription in endothelial cells initiates at four
      sites. Reporter gene expression directed by the promoter was 125-fold greater
      than vector alone in bovine aortic endothelial cells but less than 2-fold vector
      alone in non-endothelial (COS) cells, confirming that specificity in vivo was
      paralleled in vitro. The addition of 2.7 kbp of 5'-flanking region to the 0.33
      kbp fragment had no effect on promoter activity or specificity. The mutation of
      an Sp1 motif centered at base pair -194 or an eight-base pair palindrome at -268
      each reduced promoter activity by 70%. Mutation of GATA motifs at -145 and -53
      reduced promoter activity by 78 and 61%, respectively. Specific binding of bovine
      aortic endothelial cells nuclear proteins to the Sp1 and GATA sites was
      demonstrated by gel shift analysis. Promoter activity in COS cells was
      transactivated 3-4-fold by overexpression of GATA-2. The results presented here
      suggest that transcription from the ICAM-2 promoter in endothelial cells is
      regulated by the interplay of several positive-acting factors and provide the
      basis for further analysis of endothelial-specific gene expression.

PMID- 9565597
TI  - Cloning and expression of a novel K+ channel regulatory protein, KChAP.
AB  - Voltage-gated K+ (Kv) channels are important in the physiology of both excitable
      and nonexcitable cells. The diversity in Kv currents is reflected in multiple Kv
      channel genes whose products may assemble as multisubunit heteromeric complexes.
      Given the fundamental importance and diversity of Kv channels, surprisingly
      little is known regarding the cellular mechanisms regulating their synthesis,
      assembly, and metabolism. To begin to dissect these processes, we have used the
      yeast two-hybrid system to identify cytoplasmic regulatory molecules that
      interact with Kv channel proteins. Here we report the cloning of a novel gene
      encoding a Kv channel binding protein (KChAP, for K+ channel-associated protein),
      which modulates the expression of Kv2 channels in heterologous expression system
      assays. KChAP interacts with the N termini of Kvalpha2 subunits, as well as the N
      termini of Kvalpha1 and the C termini of Kvbeta subunits. Kv2.1 and KChAP were
      coimmunoprecipitated from in vitro translation reactions supporting a direct
      interaction between the two proteins. The amplitudes of Kv2. 1 and Kv2.2 currents
      are enhanced dramatically in Xenopus oocytes coexpressing KChAP, but channel
      kinetics and gating are unaffected. Although KChAP binds to Kv1.5, it has no
      effect on Kv1.5 currents. We suggest that KChAP may act as a novel type of
      chaperone protein to facilitate the cell surface expression of Kv2 channels.

PMID- 9565598
TI  - Characterization of the glycosyltransferase enzyme from the Escherichia coli K5
      capsule gene cluster and identification and characterization of the glucuronyl
      active site.
AB  - Bacterial capsular polysaccharides play an important role in virulence and
      survival. The Escherichia coli K5 capsule consists of a repeat structure of 
      4)GlcA-beta(1,4)-GlcNAc alpha(1-, identical to N-acetylheparosan. A 60-kDa
      protein, KfiC, has been identified as a bifunctional glycosyltransferase,
      responsible for the alternating alpha and beta addition of each UDP-sugar to the
      nonreducing end of the polysaccharide chain. Using hydrophobic cluster analysis,
      a conserved secondary structure motif characteristic of beta-glycosyltransferases
      was identified along with two highly conserved aspartic acid residues at
      positions 301 and 352 within the KfiC protein. Site-directed mutagenesis was used
      to identify catalytically active amino acids within domain A of the KfiC protein.
      The conserved aspartic acid residues at 301 and 352 were shown to be critical for
      the beta addition of UDP-GlcA (uridine diphosphoglucuronic acid) to defined
      nonreducing end oligosaccharide acceptors, suggesting that these conserved
      aspartic acid residues are catalytically important for beta-glycosyltransferase
      activity. A deleted derivative of the kfiC gene was generated, which encoded for
      a truncated KfiC (kfiC') protein. This protein lacked 139 amino acids at the C
      terminus. This enzyme had no UDP-GlcA transferase activity but still retained UDP
      GlcNAc transferase activity, indicating that two separate active sites are
      present within the KfiC protein.

PMID- 9565599
TI  - Biochemical evidence that small proline-rich proteins and trichohyalin function
      in epithelia by modulation of the biomechanical properties of their cornified
      cell envelopes.
AB  - The cornified cell envelope (CE) is a specialized structure involved in barrier
      function in stratified squamous epithelia, and is assembled by transglutaminase
      cross-linking of several proteins. Murine forestomach epithelium undergoes
      particularly rigorous mechanical trauma, and these CEs contain the highest known
      content of small proline-rich proteins (SPRs). Sequencing analyses of these CEs
      revealed that SPRs function as cross-bridgers by joining other proteins by use of
      multiple adjacent glutamines and lysines on only the amino and carboxyl termini
      and in functionally non-polar ways. Forestomach CEs also use trichohyalin as a
      novel cross-bridging protein. We performed mathematical modeling of amino acid
      compositions of the CEs of mouse and human epidermis of different body sites.
      Although the sum of loricrin + SPRs was conserved, the amount of SPRs varied in
      relation to the presumed physical requirements of the tissues. Our data suggest
      that SPRs could serve as modifiers of a composite CE material composed of mostly
      loricrin; we propose that increasing amounts of cross-bridging SPRs modify the
      structure of the CE, just as cross-linking proteins strengthen other types of
      tissues. In this way, different epithelia may use varying amounts of the cross
      bridging SPRs to alter the biomechanical properties of the tissue in accordance
      with specific physical requirements and functions.

PMID- 9565600
TI  - Primary and tertiary structures of the Fab fragment of a monoclonal anti-E
      selectin 7A9 antibody that inhibits neutrophil attachment to endothelial cells.
AB  - The murine monoclonal IgG1 antibody 7A9 binds specifically to the endothelial
      leukocyte adhesion molecule-1 (E-selectin), inhibiting the attachment of
      neutrophils to endothelial cells. The primary and three-dimensional structures of
      the Fab fragment of 7A9 are reported. The amino acid sequence was determined by
      automated Edman degradation analysis of proteolytic fragments of both the heavy
      and light chains of the Fab. The sequences of the two chains are consistent with
      that of the IgG1 class with an associated kappa light chain with two intrachain
      disulfide bridges in each of the heavy and light chains. The tertiary structure
      of the antibody fragment was determined by x-ray crystallographic methods at 2.8
      A resolution. The F(ab')2 molecule, treated with dithiothreitol, crystallizes in
      the space group P2(1) 2(1) 2(1) with unit cell parameters a = 44.5 A, b = 83.8 A,
      and c = 132.5 A with one Fab molecule in the asymmetric unit. The structure was
      solved by the molecular replacement method and subsequently refined using
      simulated annealing followed by conventional least squares optimization of the
      coordinates. The resulting model has reasonable stereochemistry with an R factor
      of 0.195. The 7A9 Fab structure has an elbow bend of 162 degrees and is
      remarkably similar to that of the monoclonal anti-intercellular adhesion molecule
      1 (ICAM-1) antibody Fab fragment. The 7A9 antigen combining site presents a
      groove resembling the structure of the anti-ICAM-1 antibody, and other antibodies
      raised against surface receptors and peptides. Residues from the six
      complementary determining regions (CDRs) and framework residues form the floor
      and walls of the groove that is approximately 22 A wide and 8 A deep and that is
      lined with many aromatic residues. The groove is large enough to accommodate the
      loop between beta-strands beta4 and beta5 of the lectin domain of E-selectin that
      has been implicated in neutrophil adhesion (1).

PMID- 9565601
TI  - The hydrophobic face orientation of apolipoprotein A-I amphipathic helix domain
      143-164 regulates lecithin:cholesterol acyltransferase activation.
AB  - Apolipoprotein A-I (apoA-I) activates the plasma enzyme lecithin:cholesterol
      acyltransferase (LCAT), catalyzing the rapid conversion of lipoprotein
      cholesterol to cholesterol ester. Structural mutants of apoA-I have been used to
      study the details of apoA-I-LCAT-catalyzed cholesterol ester formation. Several
      studies have shown that the alpha-helical segments corresponding to amino acids
      143-164 and 165-186 (repeats 6 and 7) are essential for LCAT activation. In the
      present studies, we examined how the orientation of the hydrophobic face,
      independent of an increase in overall hydrophobicity, affects LCAT activation. We
      designed, expressed, and characterized a mutant, reverse of 6 apoA-I (RO6 apoA
      I), in which the primary amino acid sequence of repeat 6 (amino acids 143-164)
      was reversed from its normal orientation. This mutation rotates the hydrophobic
      face of repeat 6 approximately 80 degrees. Lipid-free RO6 apoA-I showed a marked
      stabilization when denatured by guanidine hydrochloride, but showed significant
      destabilization to guanidine hydrochloride denaturation in the lipid-bound state
      compared with wild-type apoA-I. Recombinant high density lipoprotein discs (rHDL)
      formed from RO6 apoA-I, sn-1-palmitoyl-sn-2-oleoyl phosphati-dylcholine, and
      cholesterol were approximately 12 A smaller than wild-type apoA-I rHDL. The
      reduced size suggests that one of the repeats did not effectively participate in
      phospholipid binding and organization. The sn-1-palmitoyl-sn-2-oleoyl
      phosphatidylcholine RO6 rHDL were a less effective substrate for LCAT. Mapping
      the entire lipid-free and lipid-bound RO6 apoA-I with a series of monoclonal
      antibodies revealed that both the lipid-free and lipid-bound RO6 apoA-I displayed
      altered or absent epitopes in domains within and adjacent to repeat 6. Together,
      these results suggest that the proper alignment and orientation of the
      hydrophobic face of repeat 6 is an important determinant for maintaining and
      stabilizing helix-bilayer and helix-helix interactions.

PMID- 9565602
TI  - Multivalent DNA binding complex generated by small Maf and Bach1 as a possible
      biochemical basis for beta-globin locus control region complex.
AB  - The human beta-globin locus control region (LCR) is required to properly regulate
      chromatin domain opening, replication timing, and globin gene activation. The LCR
      contains multiple NF-E2 sites (Maf recognition elements, MAREs) that allow the
      binding of various basic leucine zipper (bZip) proteins like p45 NF-E2, Nrf1,
      Nrf2, Bach1, and Bach2, in some cases as obligate heterodimers with a small Maf
      protein. In addition to the bZip domain, the Bach proteins bear a BTB/POZ domain,
      which has been implicated in the regulation of chromatin structure. We show here
      that Bach1 is highly expressed in hematopoietic cells and constitutes one of the
      two MARE-binding activities in murine erythroleukemic (MEL) cells. We further
      demonstrate that Bach1/MafK heterodimers interact with each other through the BTB
      domain, generating a multimeric and multivalent DNA binding complex. These
      results strongly implicate Bach1/MafK heterodimer as an architectural
      transcription factor that mediates interactions among multiple MAREs. Such a
      factor could then provide a model for assembly of the theoretical beta-globin LCR
      "holocomplex. " Other BTB domain proteins have already been demonstrated to be
      involved in remodeling chromatin, and thus this class of proteins likely promote
      the formation of nucleoprotein complexes required to establish the architecture
      of regulatory domains.

PMID- 9565603
TI  - Purification and characterization of a polyisoprenyl phosphate phosphatase from
      pig brain. Possible dual specificity.
AB  - Microsomal fractions from pig and calf brain catalyze the enzymatic
      dephosphorylation of endogenous and exogenous dolichyl monophosphate (Dol-P)
      (Sumbilla, C. A., and Waechter, C. J. (1985) Methods Enzymol. 111, 471-482). The
      Dol-P phosphatase (EC 3.1.3.51) has been solubilized by extracting pig brain
      microsomes with the nonionic detergent Nonidet P-40 and purified approximately
      1,107-fold by a combination of anion exchange chromatography, polyethylene glycol
      fractionation, dye-ligand chromatography, and wheat germ agglutinin affinity
      chromatography. Treatment of the enzyme with neuraminidase prevented binding to
      wheat germ agglutinin-Sepharose, indicating the presence of one or more N
      acetylneuraminyl residues per molecule of enzyme. When the highly purified
      polyisoprenyl phosphate phosphatase was analyzed by SDS-polyacrylamide gel
      electrophoresis, a major 33-kDa polypeptide was observed. Enzymatic
      dephosphorylation of Dol-P by the purified phosphatase was 1) optimal at pH 7; 2)
      potently inhibited by F-, orthovanadate, and Zn2+ > Co2+ > Mn2+ but unaffected by
      Mg2+; 3) exhibited an approximate Km for C95-Dol-P of 45 microM; and 4) was
      sensitive to N-ethylmaleimide, phenylglyoxal, and diethylpyrocarbonate. The pig
      brain phosphatase did not dephosphorylate glucose 6-phosphate, mannose 6
      phosphate, 5'-AMP, or p-nitrophenylphosphate, but it dephosphorylated dioleoyl
      phosphatidic acid at initial rates similar to those determined for Dol-P. Based
      on the virtually identical sensitivity of Dol-P and phosphatidic acid
      dephosphorylation by the highly purified enzyme to N-ethylmaleimide, F-,
      phenylglyoxal, and diethylpyrocarbonate, both substrates appear to be hydrolyzed
      by a single enzyme with an apparent dual specificity. This is the first report of
      the purification of a neutral Dol-P phosphatase from mammalian tissues. Although
      the enzyme is Mg2+-independent and capable of dephosphorylating Dol-P and PA,
      several enzymological properties distinguish this lipid phosphomonoesterase from
      PAP2.

PMID- 9565604
TI  - Differential myeloma cell responsiveness to interferon-alpha correlates with
      differential induction of p19(INK4d) and cyclin D2 expression.
AB  - Interferon-alpha (IFN-alpha) has been used as therapy for the treatment of a
      variety of viral diseases and malignancies including multiple myeloma. The
      effectiveness of interferon-alpha in treating multiple myeloma, however, has been
      somewhat variable, and the mechanism(s) accounting for this is not well
      understood. As a means to examine the basis for the differential effectiveness of
      this cytokine, we have analyzed IFN-alpha-mediated modulation of the cell cycle
      in two human myeloma cell lines. These two cell lines, ANBL-6 and KAS-6/1,
      display dramatically different outcomes in response to this cytokine. Although
      IFN-alpha inhibited the growth of ANBL-6 cells by blocking cell cycle progression
      from G0/G1 to S phase, IFN-alpha stimulated cell cycle progression in KAS-6/1
      cells. Moreover, the effects of IFN-alpha on cell cycle progression correlated
      with the phosphorylation status of the retinoblastoma protein. Of interest, IFN
      alpha increased cyclin D2 expression and cyclin-dependent kinase activity in the
      KAS-6/1 cells but not in the ANBL-6 cells. To determine whether the differential
      effects of IFN-alpha on myeloma cell cycle progression could also result from
      differences in the expression of cyclin-dependent kinase inhibitors, we examined
      the effects of IFN-alpha on the induction of cyclin-dependent kinase inhibitors
      with broad regulatory function (p21 and p27) and those with specificity for G1
      associated cyclin-cyclin-dependent kinase complexes (p15, p16, p18, and p19).
      Although we failed to detect an effect of IFN-alpha on expression levels of p21,
      p15, p16, or p18, IFN-alpha treatment of the ANBL-6 cell line resulted in
      induction of p19 expression, whereas it was without effect on the KAS-6/1 cell
      line. These results suggest that heterogeneity in IFN-alpha-mediated growth
      effects in myeloma cells correlates with differential induction of cyclin D2 and
      p19(INK4d) expression.

PMID- 9565605
TI  - Instability of the amyloidogenic cystatin C variant of hereditary cerebral
      hemorrhage with amyloidosis, Icelandic type.
AB  - A cystatin C variant with L68Q substitution and a truncation of 10 NH2-terminal
      residues is the major constituent of the amyloid deposited in the cerebral
      vasculature of patients with the Icelandic form of hereditary cerebral hemorrhage
      with amyloidosis (HCHWA-I). Variant and wild type cystatin C production,
      processing, secretion, and clearance were studied in human cell lines stably
      overexpressing the cystatin C genes. Immunoblot and mass spectrometry analyses
      demonstrated monomeric cystatin C in cell homogenates and culture media. While
      cystatin C formed concentration-dependent dimers, the HCHWA-I variant dimerized
      at lower concentrations than the wild type protein. Amino-terminal sequence
      analysis revealed that the variant and normal proteins produced and secreted are
      the full-length cystatin C. Pulse-chase experiments demonstrated similar levels
      of normal and variant cystatin C production and secretion. However, the secreted
      variant cystatin C exhibited an increased susceptibility to a serine protease in
      conditioned media and in human cerebrospinal fluid, explaining its depletion from
      the cerebrospinal fluid of HCHWA-I patients. Thus, the amino acid substitution
      may induce unstable cystatin C with intact inhibitory activity and predisposition
      to self-aggregation and amyloid fibril formation.

PMID- 9565606
TI  - An RNA pseudoknot as the molecular switch for translation of the repZ gene
      encoding the replication initiator of IncIalpha plasmid ColIb-P9.
AB  - Translation initiation of the repZ gene encoding the replication initiator of
      plasmid ColIb-P9 is not only negatively regulated by the action of the antisense
      Inc RNA encoded in the leader region, but is also coupled to the translation and
      termination of a transcribed leader sequence, repY, a positive regulatory element
      for repZ gene expression. This translational coupling depends on base pairing
      between two complementary sequences, 5'-rGGCG-3' and 5'-rCGCC-3', which are
      located upstream of and in the middle of repY, respectively, and have the
      potential to form a pseudoknot with the stem-loop structure I. Another stem-loop
      called structure III near the 3'-end of repY sequesters both the 5'-rCGCC-3'
      sequence and the repZ ribosome-binding site. Here we show that the RepZ mRNA
      leader sequence synthesized in vitro indeed contains several stem-loop structures
      including structures I and III, but not the pseudoknot. However, disruption of
      structure III, without changing the repZ ribosome-binding site, by means of base
      substitution and deletion induces base pairing between the two short
      complementary sequences distantly separated, resulting in the formation of a
      pseudoknot. When the pseudoknot is allowed to form in vivo due to the same
      mutations, a maximum level of repZ expression is obtained comparable to one
      observed in the absence of Inc RNA. These results strengthen our previously
      proposed model that the pseudoknot induced by the translation and termination of
      the repY reading frame functions as the molecular switch for translational
      initiation of the repZ gene.

PMID- 9565607
TI  - Structural basis for binding of the plasmid ColIb-P9 antisense Inc RNA to its
      target RNA with the 5'-rUUGGCG-3' motif in the loop sequence.
AB  - The sequence 5'-rUUGGCG-3' is conserved within the loop regions of antisense RNAs
      or their targets involved in replication of various prokaryotic plasmids. In
      IncIalpha plasmid ColIb-P9, the partially base paired 21-nucleotide loop of a
      stem-loop called structure I within RepZ mRNA contains this hexanucleotide
      sequence, and comprises the target site for the antisense Inc RNA. In this
      report, we find that the base pairing interaction at the 5'-rGGC-3' sequence in
      the hexanucleotide motif is important for interaction between Inc RNA and
      structure I. In addition, the 21-base loop domain of structure I is folded
      tighter than predicted, with the hexanucleotide sequence at the top. The second U
      residue in the sequence is favored for Inc RNA binding in a base-specific manner.
      On the other hand, the upper domain of the Inc RNA stem-loop is loosely
      structured, and maintaining the loop sequence single-stranded is important for
      the intermolecular interaction. Based on these results, we propose that a
      structural feature in the loop I domain, conferred probably by the conserved 5'
      rUUGGCG-3' sequence, favors binding to a complementary, single-stranded RNA. This
      model also explains how the RepZ mRNA pseudoknot, described in the accompanying
      paper (Asano, K., and Mizobuchi, K. (1998) J. Biol. Chem. 273, 11815-11825) is
      formed specifically with structure I. A possible conformation adopted by the 5'
      rUUGGCG-3' loop sequence is discussed.

PMID- 9565608
TI  - Poly(ADP-ribose) binds to specific domains of p53 and alters its DNA binding
      functions.
AB  - DNA strand breaks are potential interaction sites for the nuclear enzyme poly(ADP
      ribose) polymerase (PARP; E.C. 2.4.2.30) and the tumor suppressor protein p53.
      Both proteins bind and respond to DNA breaks and both play a role in DNA damage
      signaling. A temporary colocalization and complex formation between these
      proteins has been demonstrated in mammalian cells. Here we show that free and
      poly(ADP-ribose) polymerase-bound ADP-ribose polymers target three domains in p53
      protein for strong noncovalent interactions. The polymer binding sites could be
      mapped to two amino acid sequences in the sequence-specific core DNA binding
      domain of p53 (amino acid positions 153-178 and 231-253) and another one in the
      oligomerization domain (amino acids 326-348). In mobility shift experiments,
      poly(ADP-ribose) effectively prevented and reversed p53 binding to the
      palindromic p53 consensus sequence. Additionally, poly(ADP-ribose) also
      interfered with the DNA single strand end binding of p53. The results suggest
      that ADP-ribose polymers could play a role in regulating the DNA binding
      properties of p53.

PMID- 9565609
TI  - Biochemical and biological characterization of wild-type and ATPase-deficient
      Cockayne syndrome B repair protein.
AB  - Cockayne syndrome (CS) is a nucleotide excision repair disorder characterized by
      sun (UV) sensitivity and severe developmental problems. Two genes have been shown
      to be involved: CSA and CSB. Both proteins play an essential role in preferential
      repair of transcription-blocking lesions from active genes. In this study we
      report the purification and characterization of baculovirus-produced HA-His6
      tagged CSB protein (dtCSB), using a highly efficient three-step purification
      protocol. Microinjection of dtCSB protein in CS-B fibroblasts shows that it is
      biologically functional in vivo. dtCSB exhibits DNA-dependent ATPase activity,
      stimulated by naked as well as nucleosomal DNA. Using structurally defined DNA
      oligonucleotides, we show that double-stranded DNA and double-stranded DNA with
      partial single-stranded character but not true single-stranded DNA act as
      efficient cofactors for CSB ATPase activity. Using a variety of substrates, no
      overt DNA unwinding by dtCSB could be detected, as found with other SNF2/SWI2
      family proteins. By site-directed mutagenesis the invariant lysine residue in the
      NTP-binding motif of CSB was substituted with a physicochemically related
      arginine. As expected, this mutation abolished ATPase activity. Surprisingly, the
      mutant protein was nevertheless able to partially rescue the defect in recovery
      of RNA synthesis after UV upon microinjection in CS-B fibroblasts. These results
      indicate that integrity of the conserved nucleotide-binding domain is important
      for the in vivo function of CSB but that also other properties independent from
      ATP hydrolysis may contribute to CSB biological functions.

PMID- 9565610
TI  - INP51, a yeast inositol polyphosphate 5-phosphatase required for
      phosphatidylinositol 4,5-bisphosphate homeostasis and whose absence confers a
      cold-resistant phenotype.
AB  - Sequence analysis of Saccharomyces cerevisiae chromosome IX identified a 946
      amino acid open reading frame (YIL002C), designated here as INP51, that has
      carboxyl- and amino-terminal regions similar to mammalian inositol polyphosphate
      5-phosphatases and to yeast SAC1. This two-domain primary structure resembles the
      mammalian 5-phosphatase, synaptojanin. We report that Inp51p is associated with a
      particulate fraction and that recombinant Inp51p exhibits intrinsic
      phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity. Deletion of INP51
      (inp51) results in a "cold-tolerant" phenotype, enabling significantly faster
      growth at temperatures below 15 degreesC as compared with a parental strain.
      Complementation analysis of an inp51 mutant strain demonstrates that the cold
      tolerance is strictly due to loss of 5-phosphatase catalytic activity.
      Furthermore, deletion of PLC1 in an inp51 mutant does not abrogate cold
      tolerance, indicating that Plc1p-mediated production of soluble inositol
      phosphates is not required. Cells lacking INP51 have a 2-4-fold increase in
      levels of phosphatidylinositol 4,5-bisphosphate and inositol 1,4, 5
      trisphosphate, whereas cells overexpressing Inp51p exhibit a 35% decrease in
      levels of phosphatidylinositol 4,5-bisphosphate. We conclude that INP51 function
      is critical for proper phosphatidylinositol 4,5-bisphosphate homeostasis. In
      addition, we define a novel role for a 5-phosphatase loss of function mutant that
      improves the growth of cells at colder temperatures without alteration of growth
      at normal temperatures, which may have useful commercial applications.

PMID- 9565612
TI  - Sustained long term potentiation and anxiety in mice lacking the Mas
      protooncogene.
AB  - The Mas protooncogene is a maternally imprinted gene encoding an orphan G protein
      coupled receptor expressed mainly in forebrain and testis. Here, we provide
      evidence for a function of Mas in the central nervous system. Targeted disruption
      of the Mas protooncogene leads to an increased durability of long term
      potentiation in the dentate gyrus, without affecting hippocampal morphology,
      basal synaptic transmission, and presynaptic function. In addition, Mas-/- mice
      show alterations in the onset of depotentiation. The permissive influence of Mas
      ablation on hippocampal synaptic plasticity is paralleled by behavioral changes.
      While spatial learning in the Morris water maze is not significantly influenced,
      Mas-deficient animals display an increased anxiety as assessed in the elevated
      plus maze. Thus, Mas is an important modulating factor in the electrophysiology
      of the hippocampus and is involved in behavioral pathways in the adult brain.

PMID- 9565611
TI  - Mechanical strain suppresses inducible nitric-oxide synthase in cardiac myocytes.
AB  - We investigated the effects of precisely controlled mechanical strain on nitric
      oxide synthase activity in cultured neonatal rat cardiac myocytes. Incubation of
      cardiac myocytes for 24 h with 4 ng/ml interleukin-1beta and 100 units/ml
      interferon-gamma stimulated an increase in nitric oxide production, inducible
      nitric-oxide synthase (iNOS) mRNA, and iNOS protein. Mechanical strain suppressed
      nitric oxide production, iNOS mRNA, and iNOS protein stimulated by cytokines in
      an amplitude-dependent manner. Losartan (1 microM), an angiotensin II type 1
      receptor antagonist, weakly inhibited the effect of strain, suggesting that
      paracrine angiotensin II is not the mediator of the strain effect. In addition,
      cycloheximide (10 microM), a protein synthesis inhibitor, inhibited the effect of
      strain by 46%. Transforming growth factor-beta (1 ng/ml) suppressed iNOS mRNA
      expression, but anti-transforming growth factor-beta antibody (30 microg/ml) did
      not block the effect of strain. In contrast, staurosporine (100 nM; a
      nonselective protein kinase inhibitor), calphostin C (1 microM; a selective
      protein kinase C inhibitor), and pretreatment with phorbol 12-myristate 13
      acetate abolished the effect of strain. Genistein (100 microM), a tyrosine kinase
      inhibitor, partially inhibited the effect of strain. Thus, cyclic mechanical
      deformation suppresses cytokine-induced iNOS expression in cardiac myocytes, and
      this effect is mediated at least partially via activation of protein kinase C.

PMID- 9565614
TI  - Genomic organization of Drosophila poly(ADP-ribose) polymerase and distribution
      of its mRNA during development.
AB  - Poly(ADP-ribosyl)ation of proteins catalyzed by poly(ADP-ribose) polymerase
      (PARP; EC 2.4.2.30) modulates several biological activities. However, little is
      known about the role of PARP in developmental process. Here we report the
      organization of the Drosophila PARP gene and the expression patterns during
      Drosophila development. The Drosophila PARP gene was a single copy gene mapped at
      81F and composed of six exons. Organization of exons corresponds to the
      functional domains of PARP. The DNA-binding domain was encoded by exons 1, 2, 3,
      and 4. The auto-modification domain was encoded by exon 5, and the catalytic
      domain was in exon 6. The promoter region of the PARP gene contained putative
      TATA box and CCAAT box unlike human PARP. Expression of the PARP gene was at high
      levels in embryos at 0-6 h after egg laying and gradually decreased until 8 h.
      PARP mRNA increased again at 8-12 h and was observed in pupae and adult flies but
      not in larvae. In situ mRNA hybridization of embryos revealed large amount of
      PARP mRNA observed homogeneously except the pole cells at the early stage of
      embryos, possibly due to presence of the maternal mRNA for PARP, and decreased
      gradually until the stage 12 in which stage PARP mRNA localized in anal plates.
      At late stage of embryogenesis PARP mRNA was localized in cells along the central
      nervous system.

PMID- 9565613
TI  - Production of the thyrotrophin receptor extracellular domain as a
      glycosylphosphatidylinositol-anchored membrane protein and its interaction with
      thyrotrophin and autoantibodies.
AB  - The thyrotrophin (TSH) receptor (TSHR) is synthesized as a single polypeptide
      with a predicted large extracellular domain (ECD), a seven-transmembrane pass
      region and a C-terminal intracellular tail. It is a common target for production
      of autoantibodies. To investigate whether the ECD is solely responsible for
      ligand interaction, we directed the expression of this domain in isolation on the
      cell surface by means of a glycosylphosphatidylinositol (GPI) anchor sequence.
      Immunoblotting detected TSHR material of Mr 70,000 expressed at high levels. In
      immunoprecipitation studies, the GPI-anchored ECD was recognized by experimental
      and pathological antibodies. The molecule was detected on the cell surface by
      flow cytofluorimetry at up to 10-fold higher amounts than the highest expressing
      full-length receptor clone. Radioligand binding studies confirmed this and showed
      that the recombinant molecule bound TSH with high affinity similar to full-length
      receptor; however, studies with human autoimmune sera indicated differences in
      the degree of inhibition when compared with full-length receptor. The existence
      of the GPI anchor was confirmed by cleavage with a GPI-specific phospholipase C
      and biosynthetic labeling with [3H]ethanolamine. TSHR material was also present
      inside the cell in both soluble and membrane-bound forms. Thus, the recombinant
      GPI-anchored ECD is the smallest known fragment of the TSHR that retains high
      affinity TSH binding and is expressed at high levels on the cell surface as well
      as internally; this approach may well be useful for other membrane proteins.

PMID- 9565615
TI  - Calnexin and other factors that alter translocation affect the rapid binding of
      ubiquitin to apoB in the Sec61 complex.
AB  - Several secretory proteins, including apolipoprotein B, have been shown to
      undergo degradation by proteasomes. We found that the rapid degradation of
      nascent apolipoprotein B in HepG2 cells was diminished but not abolished by the
      addition of any of three different inhibitors of proteasomes. Ubiquitin is
      conjugated to apolipoprotein B that is not assembled with sufficient lipids
      either during or soon after synthesis. In addition, we found that apolipoprotein
      B that has entered the endoplasmic reticulum sufficiently to become glycosylated
      can be degraded by proteasomes. Furthermore, we detected ubiquitin-apolipoprotein
      B that is associated with the Sec61 complex, the major constituent of the
      translocational channel. Treatment of cells with monomethylethanolamine or
      dithiothreitol decreased the translocation of apolipoprotein B and increased the
      proportion of ubiquitin-conjugated molecules associated with Sec61. Conversely,
      treatment of cells with oleic acid, which increased the proportion of
      translocated apolipoprotein B, decreased the amount of ubiquitin-apolipoprotein B
      in the Sec61 complex. Finally, we found that inhibition of the interaction
      between calnexin and apolipoprotein B decreases the translocation of
      apolipoprotein B, increases the ubiquitin-apolipoprotein B in the Sec61 complex,
      and increases the proteasomal degradation of glycosylated apolipoprotein B. Thus,
      ubiquitin can be attached to unassembled apolipoprotein B in the Sec61 complex,
      and this process is affected by factors including calnexin that alter the
      translocation of apolipoprotein B.

PMID- 9565616
TI  - Cloning and characterization of the cDNA for human airway trypsin-like protease.
AB  - Previously we isolated a trypsin-like enzyme designated human airway trypsin-like
      protease from the sputum of patients with chronic airway diseases. This paper
      describes the cDNA cloning, characterization of the primary protein structure
      deduced from the cDNA, and gene expression of this enzyme in various human
      tissues. We obtained an entire 1517-base pair sequence of cDNA with an open
      reading frame encoding a polypeptide with 418-amino acid residues. The
      polypeptide consisted of a 232-residue catalytic region and a 186-residue
      noncatalytic region with a hydrophobic putative transmembrane domain near the NH2
      terminus. The polypeptide was suggested to be a type II integral membrane protein
      in which the COOH-terminal catalytic region is extracellular. Therefore, this
      protein is thought to be synthesized as a membrane-bound precursor and to mature
      to a soluble and active protease by limited proteolysis. It showed 29-38%
      identity in the sequence of the catalytic region with human hepsin,
      enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region had
      little similarity to other known proteins. In Northern blot analysis a transcript
      of 1.9 kilobases was detectable most prominently in the trachea among 17 human
      tissues examined.

PMID- 9565617
TI  - Identification and expression in mouse of two heparan sulfate glucosaminyl N
      deacetylase/N-sulfotransferase genes.
AB  - The biosynthesis of heparan sulfate/heparin is a complex process that requires
      the coordinate action of a number of different enzymes. In close connection with
      polymerization of the polysaccharide chain, the modification reactions are
      initiated by N-deacetylation followed by N-sulfation of N-acetylglucosamine
      units. These two reactions are carried out by a single protein. Proteins with
      such dual activities were first purified and cloned from rat liver and mouse
      mastocytoma. The mouse mastocytoma enzyme is encoded by an approximately 4
      kilobase (kb) mRNA, whereas the rat liver transcript contains approximately 8 kb.
      In the present study, the primary structure of the enzyme encoded by the mouse 8
      kb transcript is described. It is demonstrated that both the 4-and 8-kb
      transcripts have a wide tissue distribution and that they are encoded by separate
      genes. Characterization of the gene encoding the 4-kb transcript demonstrates
      that it spans a region of about 8 kb and that it contains at least 14 exons. The
      similarity of this gene and the previously characterized human gene for the 8-kb
      transcript is discussed.

PMID- 9565618
TI  - c-Src is required for stimulation of gelsolin-associated phosphatidylinositol 3
      kinase.
AB  - We have shown that osteopontin binding to integrin alphav beta3 in osteoclasts
      stimulates gelsolin-associated phosphatidylinositol (PtdIns) 3-hydroxyl kinase
      (PI 3-kinase), leading to increased levels of gelsolin-bound PtdIns 3,4-P2,
      PtdIns 4,5-P2, and PtdIns 3, 4,5-P3, uncapping of barbed end actin, and actin
      filament formation. Inhibition of PI 3-kinase activity by wortmannin blocks
      osteopontin stimulation of actin filament formation, suggesting that activation
      of gelsolin-associated PI 3-kinase is an important pathway in cytoskeletal
      regulation. To study the mechanism of gelsolin-associated PI 3-kinase activation,
      we analyzed anti-gelsolin immunoprecipitates for the association of protein
      kinases. We demonstrated that c-Src co-immunoprecipitates with gelsolin, and that
      osteopontin stimulates its activity. Elimination of osteopontin-stimulated Src
      activity associated with gelsolin through antisense oligodeoxynucleotides blocked
      the stimulation of PI 3-kinase activity associated with gelsolin and the gelsolin
      dependent cytoskeletal reorganization induced by osteopontin, including increased
      F-actin levels. In addition, treatment of osteoclasts with antisense
      oligonucleotides to Src reduced bone resorption. Our results demonstrate that
      osteopontin stimulates gelsolin-associated Src, leading to increased gelsolin
      associated PI 3-kinase activity and PtdIns 3,4,5-P3 levels, which facilitate
      actin filament formation, osteoclast motility, and bone resorption.

PMID- 9565619
TI  - The role of charged amino acids in the alpha1-beta4 loop of the iron-sulfur
      protein of the cytochrome bc1 complex of yeast mitochondria.
AB  - Previous experiments using deletion mutants of the iron-sulfur protein had
      indicated that amino acid residues 138-153 might be involved in the assembly of
      this protein into the cytochrome bc1 complex. To determine which specific
      residues might be involved in the assembly process, charged amino acids located
      in the alpha1-beta4 loop of the iron-sulfur protein were mutated to uncharged
      residues and tryptophan 152 to phenylalanine. The mutant genes were used to
      transform yeast cells (JPJ1) lacking the iron-sulfur protein gene. Mutants R146I
      and W152F had almost undetectable growth in medium containing glycerol/ethanol,
      whereas mutants D143A, K148I, and D149A grew more slowly than the wild type.
      Activity of the cytochrome bc1 complex was decreased 50, 90, 67, 89, and 90% in
      mutants D143A, R146I, K148I, D149A, and W152F, respectively, but unchanged in
      mutants D139A, Q141I, D145L, and V147S. In all of these mutants except W152F, the
      cytochrome c1 content, determined by immunoblotting, was comparable with that of
      wild-type cells. However, immunoblotting revealed that the content of the iron
      sulfur protein was decreased proportionately in the five mutants with lowered
      enzymatic activity and growth suggesting that these amino acids are critical for
      maintaining the stability of the iron-sulfur protein. The efficiency of assembly
      in vitro compared with the wild type determined by selective immunoprecipitation
      was unchanged in the mutants with the exception of R146I, D149A, and W152F where
      decreases of 80, 60, and 60%, respectively, were observed suggesting that these
      amino acids are critical for the proper assembly of the iron-sulfur protein into
      the bc1 complex.

PMID- 9565620
TI  - Transcriptional regulation of the prothrombin gene in muscle.
AB  - Thrombin has been shown to mediate neurite retraction in neurons and synapse
      elimination at the neuromuscular junction. The presence of prothrombin mRNA has
      been demonstrated in brain and in muscle, but extra-hepatic regulation of the
      prothrombin gene has not been investigated. To identify cis-acting DNA elements
      involved in the expression of the prothrombin gene in muscle, we have isolated
      and analyzed a 1.3-kilobase pair promoter region of the mouse prothrombin gene.
      Using a series of transiently transfected plasmid constructs in which gene
      segments of the prothrombin promoter were linked to the luciferase gene, we have
      identified a sequence, -302 to -210, essential for prothrombin promoter activity
      in C2-myotubes. Fine analysis revealed that deletion of nucleotides between -248
      and -235 eliminated prothrombin promoter activity in C2-myotubes. Furthermore,
      electrophoretic mobility shift assays demonstrated that a nuclear factor present
      in C2-myotubes, but not in C2-myoblasts or HepG2 hepatocytes, specifically binds
      to the sequence -241 to -225. Substitutional mutation of nucleotides -237 to -231
      abolished myotube-specific promoter activity and inhibited the nuclear factor
      binding. Quantitative reverse transcription polymerase chain reaction
      demonstrated the expression of prothrombin mRNA in myotubes, but not in
      myoblasts, of primary, C2, and G8 muscle cells. This result correlates with the
      lack of prothrombin promoter activity in C2-myoblasts. The data thus suggest that
      a myotube-specific nuclear factor binds to a cis-acting sequence encompassing the
      core nucleotides -237 to -231 and plays a critical role in muscle-specific,
      differentiation-dependent expression of the mouse prothrombin gene.

PMID- 9565621
TI  - A novel splice variant of the cell death-promoting protein BAX.
AB  - Cell death plays an important role in a number of physiological processes in all
      complex multicellular organisms. One of the molecules that regulates this process
      is BAX, an integral membrane protein, that promotes apoptosis. The function of
      BAX is countered by BCL-2 and BCL-XL. The differential expression of these
      proteins can influence the ability of the cell to die or survive. In this paper,
      we describe the cloning, biochemical, and functional characterization of a novel
      splice isoform of BAX, called BAX-omega. Transient overexpression of BAX-omega
      protein potentiates cell death at levels comparable to that of BAX-alpha
      overexpression.

PMID- 9565623
TI  - Molecular ordering in HIV-induced apoptosis. Oxidative stress, activation of
      caspases, and cell survival are regulated by transaldolase.
AB  - Dysregulated apoptosis may underlie the etiology of T cell depletion by human
      immunodeficiency virus type 1 (HIV-1). We show that HIV-induced apoptosis is
      preceded by an exponential increase in reactive oxygen intermediates (ROIs)
      produced in mitochondria. This leads to caspase-3 activation, phosphatidylserine
      (PS) externalization, and GSH depletion. Since mitochondrial ROI levels are
      regulated by the supply of NADPH from the pentose phosphate pathway (PPP), the
      effect of transaldolase (TAL), a key enzyme of PPP, was investigated. Jurkat and
      H9 human CD4+ T cells were transfected with TAL expression vectors oriented in
      the sense or antisense direction. TAL overexpression down-regulated glucose-6
      phosphate dehydrogenase activities and GSH levels. Alternatively, decreased TAL
      expression up-regulated glucose-6-phosphate dehydrogenase activities and GSH
      levels. HIV-induced 1) mitochondrial ROI production, 2) caspase-3 activation, 3)
      proteolysis of poly(ADP-ribose) polymerase, and 4) PS externalization were
      accelerated in cells overexpressing TAL. In contrast, suppression of TAL
      abrogated these four activities. Thus, susceptibility to HIV-induced apoptosis
      can be regulated by TAL through controlling the balance between mitochondrial ROI
      production and the metabolic supply of reducing equivalents by the PPP. The
      dominant effect of TAL expression on oxidative stress, caspase activation, PS
      externalization, and cell death suggests that this balance plays a pivotal role
      in HIV-induced apoptosis.

PMID- 9565622
TI  - Construction and characterization of a conditionally active version of the
      serine/threonine kinase Akt.
AB  - Akt is a serine/threonine kinase that requires a functional phosphatidylinositol
      3-kinase to be stimulated by insulin and other growth factors. When directed to
      membranes by the addition of a src myristoylation sequence, Akt becomes
      constitutively active. In the present study, a conditionally active version of
      Akt was constructed by fusing the Akt containing the myristoylation sequence to
      the hormone binding domain of a mutant murine estrogen receptor that selectively
      binds 4-hydroxytamoxifen. The chimeric protein was expressed in NIH3T3 cells and
      was shown to be stimulated by hormone treatment 17-fold after only a 20-min
      treatment. This hormone treatment also stimulated an approximate 3-fold increase
      in the phosphorylation of the chimeric protein and a shift in its migration on
      SDS gels. Activation of this conditionally active Akt resulted in the rapid
      stimulation of the 70-kDa S6 kinase. This conditionally active Akt was also found
      to rapidly stimulate in these cells the phosphorylation of properties of PHAS-I,
      a key protein in the regulation of protein synthesis. The conditionally active
      Akt, when expressed in 3T3-L1 adipocytes, was also stimulated, although its rate
      and extent of activation was less then in the NIH3T3 cells. Its stimulation was
      shown to be capable of inducing glucose uptake into adipocytes by stimulating
      translocation of the insulin-responsive glucose transporter GLUT4 to the plasma
      membrane.

PMID- 9565624
TI  - Simultaneous up-regulation of viral receptor expression and DNA synthesis is
      required for increasing efficiency of retroviral hepatic gene transfer.
AB  - To understand the relative contribution of viral receptor expression and cell
      proliferation in retroviral gene transfer, we created human hepatocyte-derived
      HuH-7.MCAT-1 cell lines. These cells constitutively express the murine ecotropic
      retroviral receptor MCAT-1 without changes in morphology or proliferation states.
      The MCAT-1 receptor is also a cationic amino acid transporter, and the HuH-7.MCAT
      1.7 cells showed increased Vmax of uptake and steady-state accumulation of the
      cationic amino acids L-arginine and L-lysine. In HuH-7.MCAT-1 cells, L-arginine
      uptake was significantly up-regulated by norepinephrine and dexamethasone, and
      hepatocyte growth factor also increased L-arginine uptake along with cellular DNA
      synthesis. Gene transfer was also markedly increased in HuH-7. MCAT-1.7 cells
      incubated with an ecotropic LacZ retrovirus, and this further increased with
      hormones and hepatocyte growth factor. To define whether viral receptor up
      regulation by itself increased gene transfer, cell cycling was inhibited by a
      recombinant adenovirus expressing the Mad transcription factor (AdMad), which is
      a dominant-negative c-Myc regulator. This restricted cells in G0/G1, without
      attenuating MCAT-1 activity, as shown by flow cytometry and L-arginine uptake
      analysis, respectively. When asynchronously cycling HuH-7.MCAT-1.7 cells were
      first infected with the AdMad virus and then exposed to the ecotropic LacZ virus,
      gene transfer was virtually abolished. The data indicate that while up-regulation
      of viral receptors can greatly enhance retrovirally mediated gene transfer, DNA
      synthesis remains an absolute requirement for hepatic gene therapy with this
      approach.

PMID- 9565625
TI  - Insulin-like growth factor-1 (IGF-1) receptor-insulin receptor substrate
      complexes in the uterus. Altered signaling response to estradiol in the IGF
      1(m/m) mouse.
AB  - Some of the actions of estradiol occur through stimulation of growth factor
      pathways in target organs. Tyrosine-phosphorylated (Tyr(P)) insulin-like growth
      factor-1 receptor (IGF-1R) and the insulin receptor substrate (IRS)-1 are found
      in the uterus of mice treated with estradiol. Immunoprecipitates of uterine
      Tyr(P) IRS-1 contained both p85, the regulatory subunit of phosphatidylinositol
      (PI) 3-kinase, and PI 3-kinase catalytic activity. Estradiol also stimulated
      binding of IRS-1 and PI 3-kinase to the IGF-1R. Depletion of IRS-1 from uterine
      extracts reduced PI 3-kinase associated with the receptor, which suggests that
      binding of the enzyme to IGF-1R occurs primarily in a complex that also contains
      IRS-1. Following treatment with estradiol, formation of Tyr(P) IGF-1R, Tyr(P) IRS
      1, and the p85.IRS-1 complex was very weak in the uterus of IGF-1(m/m) mice,
      which are severely deficient in IGF-1. This indicated that most, if not all, of
      the estradiol-stimulated Tyr phosphorylation of uterine IRS-1 originates from
      ligand activation of IGF-1R kinase. IRS-2 was also Tyr-phosphorylated in the
      normal uterus and bound more IGF-1R and p85 in response to estradiol; however, a
      marked decrease in levels of uterine IRS-2 occurred 12-24 h after treatment with
      estradiol. Since IRS-2 was present in IGF-1R precipitates and a recombinant form
      of IGF-1 (long R3 IGF-1) stimulated formation of Tyr(P) IRS-2, hormonal
      activation of this docking protein probably occurs through the IGF-1R. In
      summary, our findings show that estrogen activation of uterine IGF-1R kinase
      results in enhanced binding of p85 (PI 3-kinase) to IRS-1 and IRS-2. The
      formation of one or both of these complexes may be important for the potent
      mitogenic action of this steroid. That estradiol stimulated a decrease of IRS-2,
      but not of IRS-1, suggests that these docking proteins have different roles in
      hormone-induced signaling in the uterus.

PMID- 9565626
TI  - Major histocompatibility class II-mediated signal transduction is regulated by
      the protein-tyrosine phosphatase CD45.
AB  - Major histocompatibility complex class II molecules and the B cell antigen
      receptor (BCR) transduce similar signals when cross-linked by ligand. Therefore,
      studies were conducted to determine whether the protein tyrosine phosphatase CD45
      regulates signaling via these transmembrane receptors in an analogous manner.
      Cross-linking of either class II molecules or the BCR on CD45-positive K46
      17micromlambda B lymphoma cells was observed to induce activation of the Src
      family protein- tyrosine kinase Lyn, tyrosine phosphorylation of Syk and
      phospholipase Cgamma, and the production of inositol 1,4,5-trisphosphate leading
      to intracellular mobilization as well as extracellular influx of Ca2+. In the
      absence of CD45, cross-linking of either class II molecules or the BCR failed to
      induce activation of Lyn. Syk was inducibly phosphorylated on tyrosine in a
      normal manner, whereas phospholipase Cgamma exhibited a high basal level of
      tyrosine phosphorylation that was not significantly increased upon stimulation.
      Nevertheless, phospholipase Cgamma appeared to be functional because CD45
      negative cells produced elevated levels of inositol 1,4,5-trisphosphate following
      stimulation through class II or the BCR. Regardless of this, CD45-negative cells
      exhibited Ca2+ mobilization responses that were greatly diminished and transient
      in nature. Whereas little or no mobilization of Ca2+ was observed in response to
      class II cross-linking, CD45-deficient cells mobilized Ca2+ from intracellular
      stores but not the extracellular environment in response to BCR cross-linking.
      These results demonstrate that CD45 regulates both Src family kinase activation
      and Ca2+ mobilization associated with class II- and BCR-mediated signal
      transduction.

PMID- 9565627
TI  - Abnormal properties of prion protein with insertional mutations in different cell
      types.
AB  - Inherited forms of the human transmissible spongiform encephalopathy Creutzfeldt
      Jakob disease (CJD) have been associated with mutations in the normal soluble,
      protease-sensitive form of the host prion protein (PrP-sen). Normal PrP protein
      contains five copies of a repeating eight-amino acid region, and PrP molecules
      with six or more copies of this region are associated with disease in familial
      CJD. It has been hypothesized that these mutations might facilitate spontaneous
      formation of the abnormal, aggregated protease-resistant PrP isoform, PrP-res,
      associated with clinical CJD and other transmissible spongiform encephalopathies
      (TSE). In the present experiments, hamster PrP molecules with 5 (wild-type), 7,
      9, or 11 copies of this repeat region were generated and expressed in mouse
      fibroblast cells or mouse neuroblastoma cells. In mouse fibroblast cells, mutant
      hamster PrP molecules expressing 7, 9, and 11 copies of the octapeptide repeat
      sequence showed altered cell surface expression, but both mutant and wild-type
      hamster PrP-sen molecules demonstrated abnormal properties of aggregation and
      increased protease resistance. By contrast in mouse neuroblastoma cells, hamster
      PrP-sen with 5, 9, and 11 octapeptide repeats were expressed normally on the cell
      surface, but only PrP-sen molecules with 9 or 11 copies of the repeat motif had
      abnormal properties of aggregation and increased protease resistance. Overall,
      regardless of cell type, hamster PrP molecules with greater than 7 octapeptide
      repeats were more aggregated and more protease-resistant than molecules with 7
      repeats or less. However, these abnormal molecules were at least 1000-fold less
      protease-resistant than bona fide PrP-res derived from TSE-infected brain tissue,
      and they showed no increased ability to form PrP-res in a cell-free system.

PMID- 9565628
TI  - The multiplex function of nitric oxide in (auto)immunity.

PMID- 9565629
TI  - A new look at T cells.

PMID- 9565630
TI  - Analysis of Gag-specific cytotoxic T lymphocytes in simian immunodeficiency virus
      infected rhesus monkeys by cell staining with a tetrameric major
      histocompatibility complex class I-peptide complex.
AB  - A tetrameric recombinant major histocompatibility complex (MHC) class I-peptide
      complex was used as a staining reagent in flow cytometric analyses to quantitate
      and define the phenotype of Gag-specific cytotoxic T lymphocytes (CTLs) in the
      peripheral blood of simian immunodeficiency virus macaque (SIVmac)-infected
      rhesus monkeys. The heavy chain of the rhesus monkey MHC class I molecule Mamu
      A*01 and beta2-microglobulin were refolded in the presence of an SIVmac Gag
      synthetic peptide (p11C, C-M) representing the optimal nine-amino acid peptide of
      Mamu-A*01-restricted predominant CTL epitope to create a tetrameric Mamu
      A*01/p11C, C-M complex. Tetrameric Mamu-A*01/p11C, C-M complex bound to T cells
      of SIVmac-infected, Mamu-A*01(+), but not uninfected, Mamu-A*01(+), or infected,
      Mamu-A*01(-) rhesus monkeys. Specific staining of peripheral blood mononuclear
      cells (PBMC) from SIVmac-infected, Mamu-A*01(+) rhesus monkeys was only found in
      the cluster of differentiation (CD)8alpha/beta+ T lymphocyte subset and the
      percentage of CD8alpha/beta+ T cells in the peripheral blood of four SIVmac
      infected, Mamu-A*01+ rhesus monkeys staining with this complex ranged from 0.7 to
      10.3%. Importantly, functional SIVmac Gag p11C-specific CTL activity was seen in
      sorted and expanded tetrameric Mamu-A*01/p11C, C-M complex-binding, but not
      nonbinding, CD8alpha/beta+ T cells. Furthermore, the percentage of CD8alpha/beta+
      T cells binding this tetrameric Mamu-A*01/p11C, C-M complex correlated well with
      p11C-specific cytotoxic activity as measured in both bulk and limiting dilution
      effector frequency assays. Finally, phenotypic characterization of the cells
      binding this tetrameric complex indicated that this lymphocyte population is
      heterogeneous. These studies indicate the power of this approach for examining
      virus-specific CTLs in in vivo settings.

PMID- 9565631
TI  - Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic
      T lymphocytes visualized using soluble tetrameric major histocompatibility
      complex class I-peptide complexes.
AB  - This study describes the construction of soluble major histocompatibility
      complexes consisting of the mouse class I molecule, H-2Db, chemically
      biotinylated beta2 microglobulin and a peptide epitope derived from the
      glycoprotein (GP; amino acids 33-41) of lymphocytic choriomeningitis virus
      (LCMV). Tetrameric class I complexes, which were produced by mixing the class I
      complexes with phycoerythrin-labeled neutravidin, permitted direct analysis of
      virus-specific cytotoxic T lymphocytes (CTLs) by flow cytometry. This technique
      was validated by (a) staining CD8+ cells in the spleens of transgenic mice that
      express a T cell receptor (TCR) specific for H-2Db in association with peptide
      GP33-41, and (b) by staining virus-specific CTLs in the cerebrospinal fluid of
      C57BL/6 (B6) mice that had been infected intracranially with LCMV-DOCILE.
      Staining of spleen cells isolated from B6 mice revealed that up to 40% of CD8(+)
      T cells were GP33 tetramer+ during the initial phase of LCMV infection. In
      contrast, GP33 tetramers did not stain CD8+ T cells isolated from the spleens of
      B6 mice that had been infected 2 mo previously with LCMV above the background
      levels found in naive mice. The fate of virus-specific CTLs was analyzed during
      the acute phase of infection in mice challenged both intracranially and
      intravenously with a high or low dose of LCMV-DOCILE. The results of the study
      show that the outcome of infection by LCMV is determined by antigen load alone.
      Furthermore, the data indicate that deletion of virus-specific CTLs in the
      presence of excessive antigen is preceded by TCR downregulation and is dependent
      upon perforin.

PMID- 9565632
TI  - Direct visualization of antigen-specific CD8+ T cells during the primary immune
      response to Epstein-Barr virus In vivo.
AB  - Primary infection with virus can stimulate a vigorous cytotoxic T cell response.
      The magnitude of the antigen-specific component versus the bystander component of
      a primary T cell response remains controversial. In this study, we have used
      tetrameric major histocompatibility complex-peptide complexes to directly
      visualize antigen-specific cluster of differentration (CD)8+ T cells during the
      primary immune response to Epstein-Barr virus (EBV) infection in humans. We show
      that massive expansion of activated, antigen-specific T cells occurs during the
      primary response to this virus. In one individual, T cells specific for a single
      EBV epitope comprised 44% of the total CD8+ T cells within peripheral blood. The
      majority of the antigen-specific cells had an activated/memory phenotype, with
      expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and
      CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of
      CD45RA. After recovery from AIM, the frequency of antigen-specific T cells fell
      in most donors studied, although populations of antigen-specific cells continued
      to be easily detectable for at least 3 yr.

PMID- 9565633
TI  - Exogenously provided peptides of a self-antigen can be processed into forms that
      are recognized by self-T cells.
AB  - Major histocompatibility complex (MHC) class II molecules can present peptides
      derived from two different sources. The predominant source of peptide in
      uninfected antigen presenting cells (APCs) is from self-proteins that are
      synthesized within the cell and traffic through the MHC class II compartment. The
      other source of antigen is endocytosed proteins, which includes both self- and
      foreign proteins. Foreign protein antigens generate adaptive immune responses,
      whereas self-peptides stabilize the MHC class II heterodimer on the cell surface,
      allowing positive and negative selection of thymocytes. Therefore, self-antigens
      play an important normal role in shaping the T cell receptor repertoire as well
      as a pathological role in autoimmunity. To determine whether processing and
      presentation of self-antigens by MHC class II molecules differs depending on
      whether the antigen is supplied through synthesis within the cell or by
      endocytosis, we used a T cell clone against an Ealpha peptide presented by I-Ab
      to show that processing through these two routes can differ. We also show that
      mice can be tolerant to the epitope formed through the endogenous route, but
      responsive to the epitope that can be formed through endocytosis. This suggests
      that negative selection occurs primarily against antigens that are synthesized
      within the APC, and that endocytosed self-antigens could serve as autoantigens.
      Finally, we also demonstrate that lipopolysaccharide-activated B cells are
      defective for uptake, processing, and presentation of this self-antigen, and that
      this correlates with the increased expression of the costimulatory molecules B7.1
      and B7.2. This may provide a model for studying the onset of an autoimmune
      response.

PMID- 9565634
TI  - The phosphotyrosine phosphatase SHP-2 participates in a multimeric signaling
      complex and regulates T cell receptor (TCR) coupling to the Ras/mitogen-activated
      protein kinase (MAPK) pathway in Jurkat T cells.
AB  - Src homology 2 (SH2) domain-containing phosphotyrosine phosphatases (SHPs) are
      increasingly being shown to play critical roles in protein tyrosine kinase
      mediated signaling pathways. The role of SHP-1 as a negative regulator of T cell
      receptor (TCR) signaling has been established. To further explore the function of
      the other member of this family, SHP-2, in TCR-mediated events, a catalytically
      inactive mutant SHP-2 was expressed under an inducible promoter in Jurkat T
      cells. Expression of the mutant phosphatase significantly inhibited TCR-induced
      activation of the extracellular-regulated kinase (ERK)-2 member of the mitogen
      activated protein kinase (MAPK) family, but had no effect on TCR-zeta chain
      tyrosine phosphorylation or TCR-elicited Ca2+ transients. Inactive SHP-2 was
      targeted to membranes resulting in the selective increase in tyrosine
      phosphorylation of three membrane-associated candidate SHP-2 substrates of 110
      kD, 55-60 kD, and 36 kD, respectively. Analysis of immunoprecipitates containing
      inactive SHP-2 also indicated that the 110-kD and 36-kD Grb-2-associated proteins
      were putative substrates for SHP-2. TCR-stimulation of Jurkat T cells expressing
      wild-type SHP-2 resulted in the formation of a multimeric cytosolic complex
      composed of SHP-2, Grb-2, phosphatidylinositol (PI) 3'-kinase, and p110. A
      significant proportion of this complex was shown to be membrane associated,
      presumably as a result of translocation from the cytosol. Catalytically inactive
      SHP-2, rather than the wild-type PTPase, was preferentially localized in complex
      with Grb-2 and the p85 subunit of PI 3'-kinase, suggesting that the
      dephosphorylating actions of SHP-2 may regulate the association of these
      signaling molecules to the p110 complex. Our results show that SHP-2 plays a
      critical role in linking the TCR to the Ras/MAPK pathway in Jurkat T cells, and
      also provide some insight into the molecular interactions of SHP-2 that form the
      basis of this signal transduction process.

PMID- 9565636
TI  - Disturbed CD4+ T cell homeostasis and in vitro HIV-1 susceptibility in transgenic
      mice expressing T cell line-tropic HIV-1 receptors.
AB  - T cell line-tropic (T-tropic) HIV type 1 strains enter cells by interacting with
      the cell-surface molecules CD4 and CXCR4. We have generated transgenic mice
      predominantly expressing human CD4 and CXCR4 on their CD4-positive T lymphocytes
      (CD4+ T cells). Their primary thymocytes are susceptible to T-tropic but not to
      macrophage-tropic HIV-1 infection in vitro, albeit with a viral antigen
      production less efficient than human peripheral blood mononuclear cells.
      Interestingly, even without HIV infection, transgenic mice display a CD4+ T cell
      depletion profile of peripheral blood reminiscent of that seen in AIDS patients.
      We demonstrate that CD4+ T cell trafficking in transgenic mice is biased toward
      bone marrow essentially due to CXCR4 overexpression, resulting in the severe loss
      of CD4+ T cells from circulating blood. Our data suggest that CXCR4 plays an
      important role in lymphocyte trafficking through tissues, especially between
      peripheral blood and bone marrow, participating in the regulation of lymphocyte
      homeostasis in these compartments. Based on these findings, we propose a
      hypothetical model in which the dual function of CXCR4 in HIV-1 infection and in
      lymphocyte trafficking may cooperatively induce progressive HIV-1 infection and
      CD4+ T cell decline in patients.

PMID- 9565635
TI  - A role for Fas in negative selection of thymocytes in vivo.
AB  - To seek information on the role of Fas in negative selection, we examined subsets
      of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice
      injected with graded doses of antigen. In normal mice, injection of 1-100 microg
      of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive
      Vbeta8+ cells at the level of the semi-mature population of HSAhi CD4+ 8- cells
      found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection
      also caused marked elimination of Vbeta8+ HSAhi CD4+ 8- thymocytes in lpr/lpr
      mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was
      induced by low-to-moderate doses of SEB (</=1 microg) but not by high doses (100
      microg). Similar findings applied when T cell receptor transgenic mice were
      injected with specific peptide. These findings suggest that clonal elimination of
      semi-mature medullary T cells is Fas independent at low doses of antigen but Fas
      dependent at high doses. Previous reports documenting that negative selection is
      not obviously impaired in lpr/lpr mice could thus reflect that the antigens
      studied were expressed at only a low level.

PMID- 9565637
TI  - Role of dimerization of the membrane-associated growth factor kit ligand in
      juxtacrine signaling: the Sl17H mutation affects dimerization and stability
      phenotypes in hematopoiesis.
AB  - The Kit ligand (KL)/Kit receptor pair functions in hematopoiesis, gametogenesis,
      and melanogenesis. KL is encoded at the murine steel (Sl) locus and encodes a
      membrane growth factor which may be proteolytically processed to produce soluble
      KL. The membrane-associated form of KL is critical in mediating Kit function in
      vivo. Evidence for a role of cytoplasmic domain sequences of KL comes from the
      Sl17H mutation, a splice site mutation that replaces the cytoplasmic domain with
      extraneous amino acids. Using deletion mutants and the Sl17H allele, we have
      investigated the role of the cytoplasmic domain sequences of KL in biosynthetic
      processing and cell surface presentation. The normal KL protein products are
      processed for cell surface expression, where they form dimers. Both Sl17H and the
      cytoplasmic deletion mutants of KL were processed to the cell surface; however,
      the rate of transport and protein stability were affected by the mutations.
      Deletion of cytoplasmic domain sequences of KL did not affect dimerization of KL.
      In contrast, dimerization of the Sl17H protein was reduced substantially. In
      addition, we have characterized the hematopoietic cell compartment in Sl17H
      mutant mice. The Sl17H mutation has only minor effects on hematopoiesis. Tissue
      and peritoneal mast cell numbers were reduced in mutant mice as well as in
      myeloid progenitors. Interestingly, long-term bone marrow cultures from Sl17H
      mice did not sustain the long-term production of hematopoietic cells. In
      addition, homing of normal hematopoietic progenitors to the spleen of irradiated
      Sl17H/Sl17H recipient mice was diminished in transplantation experiments,
      providing evidence for a role of Kit in homing or lodging. These results
      demonstrate that the membrane forms of KL exist as homodimers on the cell surface
      and that dimerization may play an important role in KL/Kit-mediated juxtacrine
      signaling.

PMID- 9565638
TI  - Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL
      1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in
      turpentine-induced fever development and glucocorticoid secretion.
AB  - Interleukin (IL)-1 is a major mediator of inflammation and exerts pleiotropic
      effects on the neuro-immuno-endocrine system. To elucidate pathophysiological
      roles of IL-1, we have first produced IL-1alpha/beta doubly deficient (KO) mice
      together with mice deficient in either the IL-1alpha, IL-1beta, or IL-1 receptor
      antagonist (IL-1ra) genes. These mice were born healthy, and their growth was
      normal except for IL-1ra KO mice, which showed growth retardation after weaning.
      Fever development upon injection with turpentine was suppressed in IL-1beta as
      well as IL-1alpha/beta KO mice, but not in IL-1alpha KO mice, whereas IL-1ra KO
      mice showed an elevated response. At this time, expression of IL-1beta mRNA in
      the diencephalon decreased 1.5-fold in IL-1alpha KO mice, whereas expression of
      IL-1alpha mRNA decreased >30-fold in IL-1beta KO mice, suggesting mutual
      induction between IL-1alpha and IL-1beta. This mutual induction was also
      suggested in peritoneal macrophages stimulated with lipopolysaccharide in vitro.
      In IL-1beta KO mice treated with turpentine, the induction of cyclooxygenase-2
      (EC 1.14.99.1) in the diencephalon was suppressed, whereas it was enhanced in IL
      1ra KO mice. We also found that glucocorticoid induction 8 h after turpentine
      treatment was suppressed in IL-1beta but not IL-1alpha KO mice. These
      observations suggest that IL-1beta but not IL-1alpha is crucial in febrile and
      neuro-immuno-endocrine responses, and that this is because IL-1alpha expression
      in the brain is dependent on IL-1beta. The importance of IL-1ra both in normal
      physiology and under stress is also suggested.

PMID- 9565639
TI  - Inhibition of caspases increases the sensitivity of L929 cells to necrosis
      mediated by tumor necrosis factor.
AB  - Murine L929 fibrosarcoma cells treated with tumor necrosis factor (TNF) rapidly
      die in a necrotic way, due to excessive formation of reactive oxygen
      intermediates. We investigated the role of caspases in the necrotic cell death
      pathway. When the cytokine response modifier A (CrmA), a serpin-like caspase
      inhibitor of viral origin, was stably overexpressed in L929 cells, the latter
      became 1,000-fold more sensitive to TNF-mediated cell death. In addition, TNF
      sensitization was also observed when the cells were pretreated with Ac-YVAD-cmk
      or zDEVD-fmk, which inhibits caspase-1- and caspase-3-like proteases,
      respectively. zVAD-fmk and zD-fmk, two broad-spectrum inhibitors of caspases,
      also rendered the cells more sensitive, since the half-maximal dose for TNF
      mediated necrosis decreased by a factor of 1,000. The presence of zVAD-fmk also
      resulted in a more rapid increase of TNF-mediated production of oxygen radicals.
      zVAD-fmk-dependent sensitization of TNF cytotoxicity could be completely
      inhibited by the oxygen radical scavenger butylated hydroxyanisole. These results
      indicate an involvement of caspases in protection against TNF-induced formation
      of oxygen radicals and necrosis.

PMID- 9565640
TI  - Interleukin 4 gene-defective mice reconstituted with wild-type bone marrow fail
      to produce normal immunoglobulin E levels.
AB  - The ability to reconstitute interleukin (IL)-4-/- mice with bone marrow of IL
      4+/+ mice was investigated. The absence of the IL-4-/- gene in donor or recipient
      cells did not impair the reconstitution. All immunoglobulin (Ig) subsets occurred
      at normal serum levels except for IgE and to some extent IgG1. IgE production did
      not recover in the reconstituted mice over prolonged time. However, these mice
      were competent for IgE production, because a single intrasplenic injection of IL
      4 restored IgE levels, which then remained constant. Wild-type mice reconstituted
      with wild-type bone marrow constantly had IgE serum levels comparable to
      untreated animals. In wild-type mice reconstituted with IL-4-/- bone marrow, IgE
      levels dropped gradually and disappeared by week 12. We make three unrelated but
      nonetheless important conclusions: (a) (immunoregulation) the tightly regulated
      IL-4 gene should be expressed constantly in low amounts (and with apparent
      absence of antigen stimulation) to keep the normal threshold of IgE; (b)
      (ontogeny of the immune system) an early unidentified source of IL-4 must be
      postulated which is lost in adult mice; and (c) (bone marrow transfer/gene
      therapy) under certain circumstances, the genotype of the recipient influences
      the reconstitution.

PMID- 9565641
TI  - Sequence of the spacer in the recombination signal sequence affects V(D)J
      rearrangement frequency and correlates with nonrandom Vkappa usage in vivo.
AB  - Functional variable (V), diversity (D), and joining (J) gene segments contribute
      unequally to the primary repertoire. One factor contributing to this nonrandom
      usage is the relative frequency with which the different gene segments rearrange.
      Variation from the consensus sequence in the heptamer and nonamer of the
      recombination signal sequence (RSS) is therefore considered a major factor
      affecting the relative representation of gene segments in the primary repertoire.
      In this study, we show that the sequence of the spacer is also a determinant
      factor contributing to the frequency of rearrangement. Moreover, the effect of
      the spacer on recombination rates of various human Vkappa gene segments in vitro
      correlates with their frequency of rearrangement in vivo in pre-B cells and with
      their representation in the peripheral repertoire.

PMID- 9565642
TI  - Evidence that the autoimmune antigen myelin basic protein (MBP) Ac1-9 binds
      towards one end of the major histocompatibility complex (MHC) cleft.
AB  - The NH2-terminal peptide of myelin basic protein (MBP) bound to the class II
      major histocompatibility complex (MHC) protein I-Au is an immunodominant epitope
      in experimental autoimmune encephalomyelitis, a murine model of multiple
      sclerosis. However, the MBP-I-Au complex is very unstable. To investigate this,
      we performed site-directed mutagenesis of the I-Au MHC protein and the MBP
      peptide. Biochemical, T cell activation, and molecular modeling studies of mutant
      complexes demonstrate that the MBP peptide's key residue for MHC binding, lysine
      4, is buried in the P6 pocket of I-Au, which is predominantly hydrophobic. This
      implies that the MBP-I-Au complex differs from more stable complexes in two
      respects: (a) the peptide leaves the NH2-terminal region of the MHC peptide
      binding cleft unoccupied; (b) the peptide is not anchored by typical favorable
      interactions between peptide side chains and MHC pockets. To test these
      hypotheses, a modified MBP peptide was designed based on molecular modeling, with
      the aim of producing strong I-Au binding. Extension of the NH2 terminus of MBP
      with six amino acids from the ova peptide, and replacement of the lysine side
      chain in the P6 pocket with an aromatic anchor, results in >1,000-fold increased
      binding stability. These results provide an explanation for the unusual peptide
      MHC-binding kinetics of MBP, and should facilitate an understanding of why mice
      are not tolerant to this self-peptide- MHC complex.

PMID- 9565643
TI  - Challenging cytokine redundancy: inflammatory cell movement and clinical course
      of experimental autoimmune encephalomyelitis are normal in lymphotoxin-deficient,
      but not tumor necrosis factor-deficient, mice.
AB  - Lymphotoxin (LT) is widely regarded as a proinflammatory cytokine with activities
      equivalent to tumor necrosis factor (TNF). The contribution of LT to experimental
      autoimmune encephalomyelitis (EAE) was examined using TNF/LTalpha-/- mice, TNF-/-
      mice, and a new LTalpha-/- line described here. All mice were generated directly
      in the C57BL/6 strain and used for the preparation of radiation bone marrow
      chimeras to reconstitute peripheral lymphoid organs and restore immunocompetence.
      This approach overcame the problems related to the lack of lymph nodes that
      results from LTalpha gene targeting. We show here that when LT is absent but TNF
      is present, EAE progresses normally. In contrast, when TNF is absent but LT is
      present, EAE is delayed in onset and inflammatory leukocytes fail to move
      normally into the central nervous system parenchyma, even at the peak of disease.
      In the absence of both cytokines, the clinical and histological picture is
      identical to that seen when TNF alone is deficient, including demyelination.
      Furthermore, the therapeutic inhibition of TNF and LTalpha with soluble TNF
      receptor in unmanipulated wild-type or TNF-/- mice exactly reproduces these
      outcomes. We conclude from these studies that TNF and LT are functionally
      distinct cytokines in vivo, and despite sharing common receptors, show no
      redundancy of function nor mutual compensation.

PMID- 9565645
TI  - Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in
      signal transducers and activators of transcription (STAT)6-deficient mice.
AB  - Signal transducers and activators of transcription 6 (STAT6) is essential for
      interleukin 4-mediated responses, including class switching to IgE and induction
      of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in
      vivo, we developed a murine model of allergen-induced airway inflammation.
      Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol
      increased the level of serum IgE, the number of eosinophils in bronchoalveolar
      lavage (BAL) fluid, and airway reactivity. Histological analysis revealed
      peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In
      STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were
      no eosinophilia in BAL and significantly less peribronchial inflammation than in
      wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild
      type mice. These findings suggest that STAT6 plays a crucial role in the
      pathogenesis of allergen-induced airway inflammation.

PMID- 9565644
TI  - One of the CD3epsilon subunits within a T cell receptor complex lies in close
      proximity to the Cbeta FG loop.
AB  - A recent crystal structure of the N15 alpha/beta-T cell receptor (TCR) in complex
      with an Fab derived from the H57 Cbeta-specific monoclonal antibody (mAb) shows
      the mAb fragment interacting with the elongated FG loop of the Cbeta domain. This
      loop creates one side wall of a cavity within the TCR Ti-alpha/beta constant
      region module (CalphaCbeta) while the CD and EF loops of the Calpha domain form
      another wall. The cavity size is sufficient to accommodate a single
      nonglycosylated Ig domain such as the CD3epsilon ectodomain. By using specific
      mAbs to mouse TCR-beta (H57) and CD3epsilon (2C11) subunits, we herein provide
      evidence that only one of the two CD3epsilon chains within the TCR complex is
      located in close proximity to the TCR Cbeta FG loop, in support of the above
      notion. Moreover, analysis of T cells isolated from transgenic mice expressing
      both human and mouse CD3epsilon genes shows that the heterologous human
      CD3epsilon component can replace the mouse CD3epsilon at this site. The location
      of one CD3epsilon subunit within the rigid constant domain module has
      implications for the mechanism of signal transduction throughout T cell
      development.

PMID- 9565646
TI  - Vaccination with DNA encoding an immunodominant myelin basic protein peptide
      targeted to Fc of immunoglobulin G suppresses experimental autoimmune
      encephalomyelitis.
AB  - We explore here if vaccination with DNA encoding an autoantigenic peptide can
      suppress autoimmune disease. For this purpose we used experimental autoimmune
      encephalomyelitis (EAE), which is an autoaggressive disease in the central
      nervous system and an animal model for multiple sclerosis. Lewis rats were
      vaccinated with DNA encoding an encephalitogenic T cell epitope, guinea pig
      myelin basic protein peptide 68-85 (MBP68-85), before induction of EAE with MBP68
      85 in complete Freund's adjuvant. Compared to vaccination with a control DNA
      construct, the vaccination suppressed clinical and histopathological signs of
      EAE, and reduced the interferon gamma production after challenge with MBP68-85.
      Targeting of the gene product to Fc of IgG was essential for this effect. There
      were no signs of a Th2 cytokine bias. Our data suggest that DNA vaccines encoding
      autoantigenic peptides may be useful tools in controlling autoimmune disease.

PMID- 9565647
TI  - Structural and comparative analysis of the mouse gene for pigment epithelium
      derived factor (PEDF).
AB  - PURPOSE: Pigment epithelium-derived factor (PEDF), a neurotrophic protein, is a
      member of the serine protease inhibitor supergene family. PEDF promotes both
      neuronal phenotype in cultured Y79 cells and neuronal survival in cultured
      cerebellar granulocytes. The purpose of this study was to clone the mouse PEDF
      gene and to determine its structure and levels of expression in different
      tissues. METHODS: The mouse PEDF cDNA was cloned from a mouse liver cDNA library
      using human PEDF cDNA as a probe. The mouse PEDF gene was cloned from a mouse ES
      genomic P1 library. DNA sequencing was performed using a PE-Applied Biosystems
      model 373 automated fluorescent sequencer. RESULTS: The mouse PEDF cDNA is 1461
      bp in length and contains an open reading frame of 417 amino acids. The mouse
      PEDF gene spans approximately 13 kb and, like the human, it is fragmented into 8
      exons. The splice sites follow the AG/GT consensus rule. Southern blot analysis
      indicates that the mouse genome contains only one gene for PEDF. Northern blot
      analysis shows the presence of the PEDF transcript in a broad range of adult
      mouse tissues with liver showing the highest level of expression. CONCLUSIONS:
      The mouse and human PEDF promoters share overall 27% similarity but are nearly
      identical between mouse +86 to -166 and human +102 to -96. The present study will
      allow us to move from in vitro experiments to in vivo studies through the
      development of a "knock-out" mouse model.

PMID- 9565648
TI  - Cloning and mapping the mouse Crygs gene and non-lens expression of [gamma]S
      crystallin.
AB  - PURPOSE: [gamma]-Crystallins are major structural proteins of the eye lens. While
      other crystallins have revealed distinct non-lens functions and patterns of
      expression, [gamma]-crystallins have generally appeared to be the most lens
      specific of the crystallins. Here we examine the mouse [gamma]S-crystallin
      ([gamma]S) gene and its expression. METHODS: The cDNA and gene for mouse [gamma]S
      were cloned and sequenced. The Crygs gene was mapped using genetic crosses.
      Expression patterns in mouse and cow were examined by northern blot, PCR and
      western blot using a specific peptide antibody. RESULTS: The Crygs gene was
      sequenced and mapped to mouse chromosome 16, at or near the locus for the genetic
      cataract Opj. Northern blots of tissues from new born mice, showed lens specific
      expression of [gamma]S. However, in the mature mouse eye there was, in addition,
      clear non-lens expression of [gamma]S. In the adult bovine eye RT-PCR shows that
      [gamma]S is expressed in lens, retina and cornea. A peptide antibody directed
      against [gamma]S detects bands of the expected size in western blots of mouse
      lens and in 33 day old mouse retina. CONCLUSIONS: These results suggest that
      [gamma]-crystallins have a non-crystallin role outside the lens, one which may
      predate the lens in evolutionary terms. Non-lens expression seems to increase
      with age in young mice, hinting that [gamma]S may have a role similar to that of
      a stress protein in tissues of the eye, perhaps related to accumulating insults
      resulting from light exposure.

PMID- 9565649
TI  - Biomembrane affinity chromatographic analysis of inhibitor binding to the human
      red cell nucleoside transporter in immobilized cells, vesicles and
      proteoliposomes.
AB  - The affinity of the human red cell nucleoside transporter for the transport
      inhibitor nitrobenzylthioinosine decreases upon protein purification. The
      affinity was highest for the whole cells (Kd, 0.04 nM), lowered upon cytoskeleton
      depletion (Kd, 0.2 nM) and lowest after partial purification and reconstitution
      (Kd, 0.3 nM), as determined by frontal affinity chromatography.

PMID- 9565650
TI  - Luteinizing hormone receptors are associated with non-receptor plasma membrane
      proteins on bovine luteal cell membranes.
AB  - Biophysical studies of the bovine luteinizing hormone (LH) receptor on luteal
      cell membranes suggest that this receptor may be part of a larger molecular
      weight structure. We have used 5-iodonaphthyl-1-azide (INA) to identify plasma
      membrane proteins near LH receptors on plasma membranes from bovine corpora
      lutea. Following binding of eosin isothiocyanate-derivatized ovine LH or human
      chorionic gonadotropin (hCG), five proteins with molecular weights of 71, 57, 55,
      49 and 36 kDa were selectively derivatized with [125I]-INA following 2 h exposure
      at 22 degreesC to 514 nm light. However, there was no fluorescence energy
      transfer between LH receptors occupied by ovine LH or hCG indicating that LH
      receptors were not self-associated in these membrane preparations. Together these
      results suggest that, following hormone binding, single copies of the LH receptor
      may exist in large molecular weight structures that include non-receptor
      proteins.

PMID- 9565652
TI  - Preparation of immunoliposomes directed against CD34 antigen as target.
AB  - The My-10 monoclonal antibody has facilitated the search of haematopoietic stem
      cells by recognizing selectively the human CD34 antigen. In the present work, My
      10 immunoliposomes directed specifically against CD34+ cells were prepared,
      characterized and tested in vitro. Binding to target cells at 4 degreesC of
      immunoliposomes containing carboxyfluorescein as aqueous marker was evaluated by
      flow cytometry and fluorescence microscopy. These immunoliposomes demonstrated
      their capacity to bind specifically to CD34+ cells. Studies have shown that 9
      antibodies/vesicle were sufficient to obtain a good binding efficiency. The
      product was stable over one month at 4 degreesC in terms of leakage of
      encapsulated carboxyfluorescein, particle size and antigen binding capacity.

PMID- 9565651
TI  - Membrane fusion mediated by ricin and viscumin.
AB  - The ribosome inactivating plant proteins (RIPs) ricin and viscumin but not
      Ricinus communis agglutinin are able induce vesicle-vesicle fusion. A model is
      suggested in which the toxicity of the RIPs is partially determined by their
      fusogenicity. Herein, fusion is hypothesized to allow the RIPs to leak across
      endocytic vesicles to approve their access to cytoplasmic ribosomes.

PMID- 9565653
TI  - Sequence and phylogenetic analysis of the Borrelia burgdorferi secA gene.
AB  - A Borrelia burgdorferi secA homologue was cloned and the complete DNA sequence
      was determined. The deduced protein sequence consists of 899 amino acids and
      shows a high degree of homology to SecA homologues from other Bacteria and
      photosynthetic plastids. The presence of the secA gene in Spirochetes suggests
      that this gene is present in most if not all major lineages within Bacteria. The
      ease of isolation of secA by conservation of its ATP-binding motifs combined with
      its extreme conservation in protein secretion pathways and the presence of a
      phylogenetic sequence marker in one of its ATP-binding domains makes this gene
      useful for phylogenetic analysis of Bacteria and photosynthetic plastids.

PMID- 9565654
TI  - Interactions between liposomes and human skin in vitro, a confocal laser scanning
      microscopy study.
AB  - One major problem in (trans)dermal drug delivery is the low penetration rate of
      drugs through the barrier of the skin. Encapsulation of a drug in lipid vesicles
      is one strategy to increase the penetration rate of a drug across the skin. In
      this study, the interactions between fluorescent-labelled liposomes and skin are
      visualized by confocal laser scanning microscopy (CLSM). Bilayer labelled gel
      state and liquid-state liposomes (conventional or with flexible bilayers) were
      non-occlusively applied on human skin in vitro. The penetration pathway and
      penetration depth of the lipophilic fluorescent label into the skin were
      visualized. From the CLSM images, it was clear that the label applied in micelles
      and gel-state liposomes did not penetrate as deep into the skin as the label
      applied in liquid-state vesicles. Among the liquid-state vesicles, the
      suspensions with the flexible bilayers showed the highest fluorescence intensity
      in the dermis. Thus, the thermodynamic state of the bilayer and, to a smaller
      extent, the flexibility of the bilayer influence, strongly the penetration depth
      of the label into the skin. The label applied non-occlusively in flexible
      liposomes penetrated deeper into the skin than after occlusive application.

PMID- 9565655
TI  - Membrane topology of the rat brain Na+-Ca2+ exchanger.
AB  - To provide experimental evidence for the topology of the Na+-Ca2+ exchanger
      protein NCX1 in the membrane, indirect immunofluorescence studies using site
      specific anti-peptide antibodies and Flag-epitope insertion into chosen locations
      of the protein were carried out. Anti-peptide antibodies AbO-6 and AbO-8 were
      raised against peptide segments present in a large hydrophilic loop of about 500
      amino acids, which separates the hydrophobic amino terminal part of the protein
      from the hydrophobic carboxy terminal. AbO-10 was raised against the C-terminal
      tail of the protein. All three antibodies bound to the exchanger protein
      expressed in transfected cells, in rat brain synaptic plasma membrane and in dog
      sarcolemmal preparations. The antibodies bound only to those NCX1 isoforms that
      contained the epitope against which they were raised. Detection of the exchanger
      protein in transfected cells in situ required the addition of permeabilizing
      agents suggesting an intracellular location of the epitopes to which AbO-6, AbO-8
      and AbO-10 bind. The Flag epitope was inserted into ten putative extramembraneous
      segments along the exchanger protein. For topology studies, only the Flag-mutants
      that retained Na+-Ca2+ exchange activity in whole HeLa cells, were used.
      Immunofluorescence studies indicated, that the N-terminal of the protein is
      extracellular, the first hydrophilic loop separating transmembrane helices 1 and
      2 as well as the C-terminal, are intracellular.

PMID- 9565656
TI  - Transgene expression kinetics after transfection with cationic phosphonolipids in
      hematopoietic non adherent cells.
AB  - Cationic lipids are considered to be capable of efficiently and safely mediating
      DNA transfer into cells, although expression is transient. A new family of
      cationic lipids, called phosphonolipids, has been developed, with the
      relationship between the hydrophobic domain of the lipid molecules and the
      significant enhancement of transduction efficiency in a non-adherent cell line
      characterised in the present study. The kinetics of transfection efficiency were
      also investigated. Our results demonstrate that the peak of the transient
      expression of these reporter genes mediated by cationic lipids occurred within 3
      to 14 days, depending on the aliphatic chain length of the complex used and on
      its formulation in the presence or absence of DOPE. Furthermore, the kinetics of
      transgene expression were found to differ in adherent and non-adherent cells.
      These results were obtained using three different techniques: CPRG, luminescence,
      and FACS-gal, and were in agreement with electron microscopy studies. We thus
      hypothesized that the plasma membrane composition of cells could affect the
      efficiency of transfection with cationic lipids. Our results suggest that
      phosphonolipids constitute a promising class of compounds for gene transfer
      protocols, and that galenic optimization should improve and modify the
      transfection efficiency of these DNA-lipid complexes.

PMID- 9565658
TI  - Miscibility of phospholipids with identical headgroups and acyl chain lengths
      differing by two methylene units: effects of headgroup structure and headgroup
      charge.
AB  - We have investigated the influence of the chemical structure and charge of the
      hydrophillic headgroup on the miscibility of saturated phospholipids with acyl
      chain lengths differing by two methylene units, namely DMPA/DPPA, DMPC/DPPC,
      DMPE/DPPE and DMPG/DPPG (0.1 M NaCl). All four mixtures were analysed by DSC at
      pH 7. To study the influence of a change in headgroup charge, we additionally
      investigated DMPA/DPPA mixtures at pH 4 and 12, and DMPG/DPPG mixtures at pH 2.
      The experimental DSC thermograms were fitted using methods described before
      [Johann et al., Biophys. J. 71 (1996), 3215-3228] to obtain the temperatures of
      onset and end of melting and first approximations for the non-ideality parameters
      as a function of composition. The resulting phase diagrams were then fitted using
      a four non-ideality parameter model for non-ideal, non-symmetric mixing in both
      phases. The phase diagram of the system DMPG/DPPG has a lens-like shape, the non
      ideality parameters rhog and rhol for the gel and the liquid-crystalline phase,
      respectively, are zero, indicating ideal mixing in both phases. For the other
      mixtures, differences in miscibility are observed depending on the structure of
      the headgroup. At pH 7, rhog > rhol, i.e., the miscibility in the liquid
      crystalline phase is more ideal than in the gel state. All rhog values are
      positive and the sequence for rhog observed is PA>PE>PC>PG. Partial protonation
      of PA at pH 4 or complete deprotonation at pH 12 leads to negative non-ideality
      parameters for both phases, indicating a preference for mixed pair formation.
      Protonation of PG in DMPG/DPPG mixtures at pH 2 leads to positive non-ideality
      parameters for both phases, indicating a tendency for demixing. The results show,
      that the miscibility of phospholipids with identical headgroups but chain lengths
      differing by two methylene groups is dependent on headgroup structure and on
      headgroup charge.

PMID- 9565657
TI  - Variations in the subunit content and catalytic activity of the cytochrome c
      oxidase complex from different tissues and different cardiac compartments.
AB  - The composition and activity of cytochrome c oxidase (COX) was studied in
      mitochondria from rat liver, brain, kidney and heart and also in different
      compartments of the bovine heart to see whether any correlation exists between
      known oxidative capacity and COX activity. Immunoblot analysis showed that the
      levels of ubiquitously expressed subunits IV and Vb are about 8-12-fold lower in
      liver mitochondria as compared to the heart, kidney and brain. The heart enzyme
      with higher abundance of COX IV and Vb showed lower turnover number (495) while
      the liver enzyme with lower abundance of these subunits exhibited higher turnover
      number of 750. In support of the immunoblot results, immunohistochemical analysis
      of heart and kidney tissue sections showed an intense staining with the COX Vb
      antibody as compared to the liver sections. COX Vb antibody stained certain
      tubular regions of the kidney more intensely than the other regions suggesting
      region specific variation in the subunit level. Bovine heart compartments showed
      variation in subunit levels and also differed in the kinetic parameters of COX.
      The right atrium contained relatively more Vb protein, while the left ventricle
      contained higher level of subunit VIa. COX from both the ventricles showed high
      Km for cytochrome c (23-37 microM) as compared to the atrial COX (Km 8-15
      microM). These results suggest a correlation between tissue specific oxidative
      capacity/work load and changes in subunit composition and associated changes in
      the activity of COX complex. More important, our results suggest variations based
      on the oxidative load of cell types within a tissue.

PMID- 9565659
TI  - Stimulation of the yeast mitochondrial calcium uniporter by hypotonicity and by
      ruthenium red.
AB  - The Ca2+ uptake by mitochondria from the yeast Endomyces magnusii has earlier
      been found to be driven by the membrane potential and to be stimulated by
      spermine. It thus functions in a similar fashion as the animal mitochondrial
      calcium uniporter. Here, it is shown that the uptake is stimulated, i.e., Ca2+
      can be accumulated from lower [Ca2+], under hypotonic conditions. Ruthenium Red,
      an inhibitor of the animal uniporter, under certain conditions, stimulates the
      yeast uniporter. The mechanism of the stimulation by hypotonicity and Ruthenium
      Red is discussed.

PMID- 9565660
TI  - Swelling-activated potassium currents of Ehrlich ascites tumour cells.
AB  - The K+ and Cl- currents activated by Ca2+-ionophore treatment or by hypotonic
      cell swelling have been studied in Ehrlich ascites tumour cells by the patch
      clamp technique. A charybdotoxin-inhibitable K+ current was activated by
      increasing intracellular Ca2+ concentration. In contrast, the K+ current
      activated by cell swelling was insensitive to charybdotoxin as well as to apamin,
      suggesting that channels different from those sensitive to Ca2+ are responsible
      for regulatory volume adjustments in these cells. The magnitude of the K+ and Cl-
      currents activated by hypotonic challenge was markedly temperature-dependent,
      possibly reflecting the temperature-dependence of enzymes involved in the
      intracellular signalling of cell volume regulation.

PMID- 9565661
TI  - Characterization of the pH dependence of hemoglobin binding to band 3. Evidence
      for a pH-dependent conformational change within the hemoglobin-band 3 complex.
AB  - The pH dependence of hemoglobin binding to inside-out red cell membrane vesicles
      was studied using 90 degrees light scattering (Salhany, J.M. et al., Biochemistry
      19 (1980) 1447-1454). Hyperbolic binding curves were observed for high-affinity
      hemoglobin binding to the cytoplasmic domain of band 3 (CDB3) within the intact
      transporter. Analysis of these saturation curves yielded the apparent Kd and the
      maximum light scattering signal change (DeltaLSmax ). The apparent Kd for
      hemoglobin binding did not change substantially between pH 5.5 and 7.0, while at
      pH 8, there is no binding. In contrast, DeltaLSmax decreased by about 20-fold
      between pH 5.5 and 7.0, with an apparent pK of 6.5. These results suggest that
      hemoglobin binds to CDB3 with high affinity at both neutral and acid pH, a
      suggestion that was confirmed using a centrifugation method. Thus, the pK for the
      light scattering signal change is significantly lower than the pK for the actual
      binding process. We show that the change in DeltaLSmax is not related to a change
      in band 3 binding capacity, which remains constant as a function of pH. We also
      show that hemoglobin binding to non-band 3 sites contributes less than 10% to
      DeltaLSmax under our specific experimental conditions. On the basis of these and
      previous fluorescence quenching results in the literature, we propose a new model
      for hemoglobin binding to band 3, where raising the pH from 6 and 7 causes the
      CDB3-hemoglobin complex to undergo a conformational change leading to the
      movement of the bound hemoglobin away from the surface of the bilayer. The
      possible implication of this new mechanistic interpretation is discussed briefly.

PMID- 9565662
TI  - Effect of site-directed mutagenesis of the arginine residues 509 and 748 on mouse
      band 3 protein-mediated anion transport.
AB  - Using site-directed mutagenesis, the arginine residues 509 and 748 in mouse band
      3 protein were substituted by Lys, Thr, and Cys, or by Lys and Gln, respectively.
      After expression in Xenopus oocytes of the cRNAs encoding wild type band 3 or any
      one of the band 3 mutants, chloride equilibrium exchange was measured. When the
      flux measurements were performed two to three days after microinjection of the
      cRNAs, in contrast to the wild type, neither one of the mutants was able to
      accomplish transport, with the possible exception of the mutants R509K and R748K
      both of which showed some transport activity of doubtful significance.
      Immunoprecipitates revealed that the Arg 748 mutants were expressed similar to
      the wild type band 3 while no expression of the Arg 509 mutants could be
      detected. When the flux measurements were performed only 3 h after microinjection
      of the cRNAs, transport activity was observed in the oocytes that had received
      cRNAs encoding wild type band 3. In some oocytes of a population, a very slight
      transport activity was brought about by cRNA encoding Arg 509 mutants. No
      transport activity could be detected after injection of the Arg 748 mutant.
      Immunoprecipitation demonstrated the successful biosynthesis of wild type band 3
      and of both the Arg 509 and the Arg 748 mutants. The experiments suggest that
      mutation of Arg 748 leads to biosynthesis of an inactive form of the band 3
      protein, while that of Arg 509 results in expression of an abnormally folded,
      possibly functionally more or less intact form, which is proteolytically degraded
      within less than one day.

PMID- 9565663
TI  - Gene structure of chick lumican and identification of the first exon.
AB  - Three overlapping genomic clones to chick lumican were isolated and then
      characterized using restriction enzyme analyses, Southern blot analyses with cDNA
      probes, and by DNA sequencing. The results showed chick lumican gene to consist
      of 3 exons with a 2.9-kb first intron and a 4.2-kb second intron. Transcription
      initiation sites, identified by S1 nuclease experiments using genomic fragments
      containing exon 1 and by primer extension analysis of RNA, indicated the first
      exon to be 303 b. Two TATA sequences were 31 and 49 bases upstream of the first
      exon. The first exon contained all 5' untranslated sequence. The second exon was
      896 b and contains 20 b of untranslated sequence, and codes for the start
      methionine to the end of the 10th leucine rich repeat. The third exon is 880 b
      and codes for the remainder of the core protein, and 724 b of untranslated 3'
      sequence. A 1-kb genomic fragment containing a portion of exon 1 and upstream
      sequence in a luciferase reporter sector showed specific promotor activity in the
      forward, but not the reverse direction when transfected into corneal fibroblasts.
      These results show the chick lumican gene to consist of three exons, and that
      regulatory elements are present within 1 kb upstream of the first exon.

PMID- 9565664
TI  - Membrane skeleton and red blood cell vesiculation at low pH.
AB  - Shapes of red blood cells at low pH were studied theoretically. It is assumed
      that the equilibrium shape of the red blood cell corresponds to the minimum of
      its membrane elastic energy which consists of the bending energy and relative
      stretching energy of the bilayer, the stretching energy of the skeleton and the
      interaction energy between the skeleton and the bilayer. It is shown that the
      aggregation of the skeleton at low pH can cause the red blood cell shape
      transformation from the stomatocytic shape to the cell shape composed of a
      spherical parent cell having the bilayer completely underlaid with the skeleton
      and spherical daughter vesicles without the skeleton.

PMID- 9565665
TI  - Isolation and functional analysis of the promoter of the rat CMP-NeuAc:GM3
      alpha2,8 sialyltransferase gene 1.
AB  - A 2.1-kb 5'-flanking fragment of the rat CMP-NeuAc:GM3 alpha2,8 sialyltransferase
      (GD3-synthase) gene was cloned by the genomic walking procedure. The promoter
      activity of the fragment was assessed in F-11 cells by transient transfection and
      the locations for the basal and maximal promoter activities were defined. Primer
      extension analysis identified a transcription start site approximately 98 bp
      upstream of the ATG start codon. DNA sequence analysis of the promoter revealed a
      number of consensus binding sites for known transcription factors such as SP1,
      AP1, NFkappaB, C/EBP and TFIID, and a repeat GC-GT sequence motif seen for the
      formation of Z-type DNA. Both TATA and CCAAT boxes were not found in the
      promoter. Our results from deletion constructs suggested that both positive and
      negative cis-acting regulatory regions were present in this TATA-less promoter of
      the rat GD3-synthase gene.

PMID- 9565666
TI  - Independence of dimethylamiloride-sensitive Li+ efflux pathways and Na+-Li+
      countertransport in human erythrocytes.
AB  - The in vivo function of the erythrocyte Na+-Li+ countertransport (SLC) is
      unknown. Whether SLC may reflect an operational mode of the widespread Na+-H+
      exchanger (NHE) or may otherwise be expression of an independent membrane
      transport, remains presently unclear. We explored the presence of 5-(N,N
      dimethyl)-amiloride (DMA)-sensitive Li+ pathways in human erythrocytes where the
      activity of the Na+ pump, Na+-K+ cotransport and anion exchange were suitably
      inhibited. A total of 0.02 mM DMA had no effect on SLC as expected, but gave a
      significant inhibition of Li+ efflux into both Na+ and Na+-free media. This DMA
      sensitive Li+ pathway, but not SLC, was significantly enhanced by hyperosmolar
      cell shrinkage, which is a characteristic feature of NHE. In conclusion, DMA
      sensitive Li+ pathways, possibly mediated by NHE, are present in erythrocytes and
      coexist with the DMA-insensitive, SLC. This finding supports the notion that SLC
      is independent of amiloride-sensitive NHE.

PMID- 9565667
TI  - A novel DEAD-box RNA helicase exhibits high sequence conservation from yeast to
      humans.
AB  - We have identified a novel Drosophila protein, DBP80, that exhibits significant
      similarity to mouse mDEAD5, yeast TIF1/2, and mammalian eIF-4A. DBP80 is a member
      of a subclass of DEAD-box proteins that contains a distinct domain,
      PX(I/R)ILLKR(E/D)EETLEGIKQ(F/Y)(F/Y), in addition to the seven canonical helicase
      domains.

PMID- 9565668
TI  - Effects of fumonisin B1 on lipid peroxidation in membranes.
AB  - Electron spin resonance (ESR)1 spin-label oximetry and spin trapping techniques
      have been used to study the effect of fumonisin B1 (FB1), an amphipathic
      mycotoxin on lipid peroxidation in egg yolk phosphatidylcholine (EYPC) bilayers.
      In the study of the interaction between FB1 and lipid bilayers our results show
      that fumonisin disturbs the ordering of membranes, enhances oxygen transport in
      membranes, and also increases membrane permeability. In our model system, lipid
      peroxidations were initiated by extended incubation of the liposomes, or by
      inducing Fe2+ ions, UV illumination of H2O2 or ultrasound irradiation. As an
      indication of the rates of lipid oxidation in EYPC, the consumption of molecular
      oxygen was studied by monitoring the oxygen concentration in the aqueous phases
      of the liposomes. Lipid-derived free radicals generated during the oxidation
      process were measured by a spin trapping method. The incorporation of FB1 in the
      test samples made the membranes highly susceptible to oxidation. Our results
      provide the first evidence that the fumonisins appear to increase the rate of
      oxidation, promote the free radical intermediate production and accelerate the
      chain reactions associated with lipid peroxidation. The disruption of membrane
      structure, the enlargement of the relative oxygen diffusion-concentration
      products, as well as the enhancement effects on membrane permeability, thus
      provide additional insights into potential mechanisms by which the fumonisins
      could enhance oxidative stress and cell damage.

PMID- 9565669
TI  - Characterization of the region downstream of the pilus biogenesis gene pilC1 in
      Neisseria gonorrhoeae.
AB  - The nucleotide sequence of a 3 kb region downstream of pilC1 in Neisseria
      gonorrhoeae MS11 was analyzed. This region contains two open reading frames, ORF1
      and ORF2, and several repetitive DNA elements. ORF1 encodes an outer membrane
      protein that shows homology to orf98 of Pediococcus acidilactici. PCR with
      primers specific for ORF1 revealed that the gene is present in all gonococcal
      strains tested. The other open reading frame, ORF2, is highly homologous to the
      putative integral membrane protein HI1680 of Haemophilus influenzae.

PMID- 9565670
TI  - Plasmids for the in vitro analysis of RNA polymerase II-dependent transcription
      based on a G-free template.
AB  - Described are a series of plasmids containing combinations of adenovirus-2 major
      late promoter elements, including consensus TATA box and initiator, upstream of G
      free transcription cassettes of various lengths. These provide an assortment of
      tools for investigating both basal and regulated transcription mechanisms by in
      vitro transcription methods.

PMID- 9565671
TI  - In vitro characterization of iron-phytosiderophore interaction with maize root
      plasma membranes: evidences for slow association kinetics.
AB  - As an attempt to characterize iron(III)-phytosiderophore transport across plant
      membranes in vitro, a rapid filtration approach was set up in which plasma
      membrane vesicles from maize roots were incubated with 55Fe-labelled
      deoxymugineic acid (DMA). Fe-DMA, and not Fe-EDTA, could associate with plasma
      membrane vesicles. The rate of Fe-DMA association decreased with a half time of
      15 min. The initial Fe-DMA association rate, estimated from the amount of Fe-DMA
      associated after 10 min incubation, exhibited a saturation curve as a function of
      Fe-DMA concentration. This curve could be satisfactorily fitted to the Michaelis
      Menten model (KM=600 nM, Vmax=2 nmol min-1 mg-1 protein). The association rate of
      Fe-DMA with control liposomes remained negligible and constant in a pH range from
      4 to 8, whereas it strongly increased at acidic pH with plasma membrane vesicles.
      However, the specific association of Fe-DMA to root plasma membrane could not be
      explained by a vesicle-filling process because: (i) lowering the vesicle volume
      by decreasing the osmotic potential of the assay medium with sorbitol did not
      decrease 55(Fe) labelling of the vesicles, (ii) creating inside-out vesicles by a
      Brij-58 treatment had almost no effect on Fe-DMA association to vesicles, (iii)
      55(Fe) labelling is reversible by EDTA and excess free DMA, and (iv) 55(Fe)
      labelling was the same using plasmalemma vesicles prepared either from wild type
      maize or from the ys1 maize mutant deficient in iron-phytosiderophore transport.
      A model is proposed to account for the observed Fe-DMA association as the result
      of very slow binding kinetics onto membrane proteins. This model was validated by
      its ability to describe quantitatively both Fe-DMA association as a function of
      time and of substrate concentration. A prediction of the model was that
      association of Fe-DMA to plasma membranes might overcome a high activation energy
      barrier. Indeed, the Arrhenius plot for the association rate constant was linear
      with an activation energy of 64 kJ mol-1.

PMID- 9565672
TI  - The gene for ribosomal protein L7a-1 in Schizosaccharomyces pombe contains an
      intron after the initiation codon.
AB  - The gene encoding ribosomal protein L7a-1 in the fission yeast
      Schizosaccharomyces pombe is identified by the similarity of its open reading
      frame to the respective gene in Saccharomyces cerevisiae. The L7a gene is encoded
      in two different genomic environments as frequently found for ribosomal protein
      genes in this organism. One of these genes, L75a-1, is located on chromosome 2.
      The two consensus promoter elements homol D and homol E are both identified
      upstream of the start codon of this gene. The ATG start codon is separated from
      the main reading frame by an intron of 66 nucleotides.

PMID- 9565673
TI  - The gene downstream of Streptomyces aureofaciens whiB encodes a large protein
      with proposed transmembrane localization, and is induced by glucose.
AB  - The sequence analysis of the region downstream of the Streptomyces aureofaciens
      whiB sporulation gene revealed a long open reading frame (1219 amino acids; Mr
      128 209) encoding protein with potential transmembrane structure. By integrative
      transformation, via double cross-over, a stable null mutant of the gene, orf1219,
      was prepared. This mutation appeared to have no obvious effect on vegetative
      growth and differentiation. In vitro and in vivo transcriptional analysis of the
      downstream gene revealed a single apparent promoter induced by glucose.

PMID- 9565674
TI  - Cloning and sequence analysis of cDNAs encoding the heavy and light chain
      variable regions of a human monoclonal antibody with specificity for hepatitis B
      surface antigen.
AB  - We cloned and analyzed the cDNA sequences encoding the variable regions of a
      human monoclonal antibody (23HN) (gamma1, kappa) that binds to the common a
      antigenic determinant on hepatitis B surface antigen and its fine epitope is
      different from those of previously known mAbs with the same specificity. The
      heavy and light chain variable regions are the members of human heavy chain
      subgroup III and kappa light chain subgroup III, respectively, and are most
      homologous to human germline VH segment DP-50 and Vkappa segment DPK-22,
      respectively.

PMID- 9565675
TI  - The exon-intron architecture of human chloride channel genes is not conserved.
AB  - The human CLCN6 gene contains a 167 bp exon that is optionally included or
      excluded in ClC-6 mRNAs. The corresponding region (3.4 kbp) of the human CLCN7
      gene has now been cloned and sequenced. A comparison of the human CLCN1, CLCN5,
      CLCN6 and CLCN7 genes indicates that there is no homologue of the optional CLCN6
      exon in the CLCN1, CLCN5 or CLCN7 genes. Thus, the CLCN6 type of alternative
      splicing and the ensuing structural diversity is not conserved within the CLC
      gene family.

PMID- 9565676
TI  - Cloning and characterization of cDNAs coding for heavy and light chains of
      agglutinating monoclonal antibody (HAG12islrh) specific for human red blood
      cells.
AB  - Complementary DNAs encoding the heavy and light chains of the Fab fragment of
      mouse agglutinating monoclonal antibody against human red blood cells were cloned
      by polymerase chain reaction and their nucleotide sequences were determined. The
      sequence analysis showed that the variable regions of the heavy and light chains
      were the members of mouse heavy-chain subgroup IIa and kappa light-chain subgroup
      I, respectively. A few unusual amino acids in the constant regions of the heavy
      chain were also recognized.

PMID- 9565677
TI  - The oxidative metabolism of catecholamines in the brain: a review.
AB  - This paper summarizes the strong evidence that we now have that the oxidative
      pathway of metabolism of the catecholamines, dopamine and norepinephrine via
      their respective quinones occurs in vivo in the brain. This fact is not yet
      widely appreciated. The evidence is based on the chemical structure of
      neuromelanin, advanced mass spectrometry techniques and the identification of
      intermediates of this system, such as 5-cysteinyl dopamine, in the brain.
      Supportive evidence is presented from a number of sources including enzymology. A
      suggestion as to the possible normal function of this system is made.

PMID- 9565678
TI  - A tellurite-resistance genetic determinant from phytopathogenic pseudomonads
      encodes a thiopurine methyltransferase: evidence of a widely-conserved family of
      methyltransferases.
AB  - A tellurite-resistance genetic determinant was isolated from the pea blight
      pathogen Pseudomonas syringae pathovar pisi by a shotgun strategy involving a
      tellurite-selective screening in Escherichia coli. A 1.65 kb tellurite resistance
      insert was obtained and analysed. It harbours a single complete and functional
      ORF encoding a deduced protein of 24, 445 Da. The deduced AA sequence shows
      significant similarities with the complete human thiopurine methyltransferase
      enzyme, a methyltransferase from Synechocystis and a methyltransferase-like
      sequence from Bordetella pertussis. The encoded thiopurine methyltransferase
      activity was demonstrated using a radiochemical microassay for the methylation of
      6-mercaptopurine. This gene was detected in most P. syringae legume pathogens.

PMID- 9565679
TI  - A novel function of enolase from rabbit muscle; an immunoglobulin production
      stimulating factor.
AB  - Rabbit muscle enolase stimulates immunoglobulin production by a human hybridoma
      line, HB4C5 cells under serum-free condition. IgM productivity of HB4C5 cells was
      enhanced more than 20-fold by this enzyme at 220 micro/ml. Human peripheral blood
      lymphocytes were also facilitated their IgM and IgG productivity in the serum
      free medium. However, baker's yeast enolase was ineffective to accelerate
      immunoglobulin production by HB4C5 cells, in spite of the same specific enzymatic
      activity as rabbit muscle enolase. There were differences in sensitivities
      against heat treatment and trypsin digestion between IPSF and enzymatic
      activities of enolase. These results imply that the immunoglobulin production
      stimulating effect of rabbit muscle enolase is irrelevant to its enzymatic
      function and reaction products. This fact also means that this enzyme has another
      function other than enzymatic one in glycolysis. Rabbit muscle enolase enhanced
      IgM production of transcription-suppressed HB4C5 cells treated with actinomycin
      D. Cycloheximide treatment of HB4C5 cells was useless to inhibit the expression
      of immunoglobulin production stimulating activity. However, inhibition of post
      transcriptional process by monensin invalidated the activity of enolase. These
      findings suggest that enolase from rabbit muscle accelerates the steps between
      translation and post-translational processes to enhance immunoglobulin
      productivity. In addition, laser confocal microscopic analysis revealed that
      enolase from rabbit muscle was subsequently incorporated by HB4C5 cells.

PMID- 9565680
TI  - Analysis and overexpression in Escherichia coli of a staphylococcal gene encoding
      seryl-tRNA synthetase.
AB  - We have sequenced and expressed in Escherichia coli the gene encoding the seryl
      tRNA synthetase from the pathogenic bacterium Staphylococcus aureus. The
      overexpressed and purified recombinant enzyme was able to aminoacylate
      unfractionated tRNA from E. coli. Its activity was not affected by antibodies
      raised against and inhibiting the E. coli seryl-tRNA synthetase.

PMID- 9565681
TI  - Cloning and sequencing of a novel murine liver carboxylesterase cDNA.
AB  - Carboxylesterases (EC 3.1.1.1) comprise a group of serine hydrolases with at
      least 20 genetically distinct loci in mice. Here, we describe differential
      display PCR-based cloning of a cDNA, encoding a novel murine carboxylesterase
      termed ES-x, which was expressed predominantly in liver but also in kidney and
      lung. The cDNA of ES-x spanned a 2249-bp sequence with an open reading frame
      encoding 565 amino acids, including an N-terminal hydrophobic signal peptide
      which directs the synthesis into microsomal lumen and a C-terminal HVEL consensus
      sequence for retaining the protein in the lumen of the endoplasmic reticulum. The
      predicted amino acid sequence of ES-x exhibited 75% identity with rat liver pI
      6.1 esterase. We further demonstrate that feeding mice with diets containing
      cholestyramine or sodium cholate increases mRNA-expression of ES-x in liver 2.5-
      to 3-fold.

PMID- 9565682
TI  - Characterization of tau phosphorylation in glycogen synthase kinase-3beta and
      cyclin dependent kinase-5 activator (p23) transfected cells.
AB  - One of the histopathological markers in Alzheimer's disease is the accumulation
      of hyperphosphorylated tau in neurons called neurofibrillary tangles (NFT)
      composing paired helical filaments (PHF). Combined tau protein kinase II (TPK
      II), which consists of CDK5 and its activator (p23), and glycogen synthase kinase
      3beta (GSK-3beta) phosphorylate tau to the PHF-form in vitro. To investigate tau
      phosphorylation by these kinases in intact cells, the phosphorylation sites were
      examined in detail using well-characterized phosphorylation-dependent anti-tau
      antibodies after overexpressing the kinases in COS-7 cells with a human tau
      isoform. The overexpression of tau in COS-7 cells showed extensive
      phosphorylation at Ser-202 and Ser-404. The p23 overexpression induced a mobility
      shift of tau, but most of the phosphorylation sites overlapped the endogenous
      phosphorylation sites. GSK-3beta transfection showed the phosphorylation at Ser
      199, Thr-231, Ser-396, and Ser-413. Triplicated transfection resulted in
      phosphorylation of tau at 8 observed sites (Ser-199, Ser-202, Thr-205, Thr-231,
      Ser-235, Ser-396, Ser-404, and Ser-413).

PMID- 9565683
TI  - A new Drosophila ultraviolet light-damaged DNA recognition endonuclease that
      selectively nicks a (6-4) photoproduct site.
AB  - We have previously described the purification of an ultraviolet light (UV) damage
      specific DNA-binding protein from Drosophila melanogaster, designated D-DDB P1
      [Nucleic Acids Res., 23 (1995) 2600-2607]. Here, we obtained highly purified D
      DDB P1 from Drosophila Kc cells, and we found that D-DDB P1 is also a nuclease. D
      DDB P1 can selectively bind to pyrimidine (6-4) pyrimidone photoproducts, and in
      the presence of Mg++, D-DDB P1 can catalyze an incision immediately on the 3' and
      5' sides of the (6-4) photoproduct site.

PMID- 9565685
TI  - Sequences flanking the E-box contribute to cooperative binding by c-Myc/Max
      heterodimers to adjacent binding sites.
AB  - Previously, we have shown that c-Myc/Max heterodimers, bind cooperatively to the
      two adjacent, canonical E-boxes (CACGTG) located in the rat ornithine
      decarboxylase (ODC) gene. In order to study this in more detail, we changed the
      length of the linker that separates the two E-boxes, as well as their flanking
      sequences. We found that high affinity, cooperative binding requires a minimal
      linker length of 1-4 bp and that the binding affinity is influenced by E-box
      flanking sequences. Binding to the c-Myc responsive element of prothymosin alpha,
      containing both a canonical and a noncanonical E-box (CAAGTG) was also studied.
      As shown by DNAseI footprinting analysis, only the canonical E-box is bound by c
      Myc/Max and c-Max/Max dimers. Replacing the noncanonical site with a canonical E
      box only partially restored high affinity, cooperative binding. By making hybrid
      fragments between ODC and prothymosin alpha, we found that nucleotides in the
      linker between the E-boxes influence the affinity of c-Myc/Max heterodimers.
      Taken together, our results show that E-box sequences and sequences in the linker
      separating both E-boxes influence cooperative, high affinity binding by c-Myc/Max
      dimers.

PMID- 9565684
TI  - In vivo roles of Bm3R1 repressor in the barbiturate-mediated induction of the
      cytochrome P450 genes (P450(BM-3) and P450(BM-)1) of Bacillus megaterium.
AB  - We previously showed [Q. Liang, A.J. Fulco, J. Biol. Chem., 270 (1995) 18606
      18614) that the binding of Bm3R1 repressor to Barbie box elements and operator
      sites in the 5'-flanking regions of the P450BM-3 and P450BM-1 (CYP102 and CYP106)
      genes in Bacillus megaterium was a critical factor in their regulation at the
      level of transcription. We now describe experiments that delineate specific roles
      for Bm3R1 in the barbiturate-mediated induction of these genes. We directly
      demonstrate the interaction of Bm3R1 with Barbie box and operator sequences and
      show that high in vivo levels of Bm3R1 prevent putative positive factors from
      binding to Barbie box elements, strongly inhibit the expression of the P450
      genes, prolong the lag phase of growth in Bacillus megaterium cultures and
      increase the sensitivity of the cells to the growth-inhibitory effects of
      barbiturates. Finally, our data suggest that there may be two forms of Bm3R1,
      either of which can interact with OIII, the bicistronic operator sequence.

PMID- 9565686
TI  - 13C-Glycogen deposition during pregnancy in the rat following routine meal
      feeding.
AB  - In vivo -NMR was employed to determine the hepatic fate of infused [1-]-d-glucose
      (200 mg/kg) following ad libitum or routine meal feeding (RMF) regimes imposed
      during pregnancy. Hepatic glycogen synthesis was measured immediately following
      the last meal in virgin, 10 and 20 day pregnant rats. No detectable incorporation
      of -glucose into glycogen was observed in 20 day pregnant and control fed virgin
      rats. In 20 day pregnant RMF rats, glycogen synthesis from -glucose occurred at a
      linear rate of 0.10/s (S.D. 0.018/s). By 50 min post-infusion, 13C-glycogen
      levels were 131% (p<0.01) higher than those seen for the 22 h starved and 2 h
      refed virgin group. Following 10 days of gestation, glucose incorporation into
      glycogen was maximal in both the ad libitum and RMF groups. Compared with the 20
      day pregnant RMF group, the 10 day pregnant ad libitum and RMF rats produced 146%
      (p<0.001) and 315% (p<0.001) more incorporation of -glucose into the glycogen
      macromolecule, respectively. Hepatic glycogen values were similar for both 10 and
      20 day pregnant ad libitum rats (65.7+/-4.7 and 58.8+/-4.5 mg/g weight) but lower
      in the RMF groups by 58% and 48%, respectively. In conclusion, meal feeding
      regimes in the pregnant rat alter carbohydrate control of the liver producing
      increased glycogen synthesis initially via direct incorporation of glucose into
      the macromolecule.

PMID- 9565687
TI  - Molecular cloning, expression and tissue distribution of canine
      lipopolysaccharide (LPS)-binding protein.
AB  - The plasma lipopolysaccharide (LPS)-binding protein (LBP) plays an important role
      in infection caused by Gram-negative bacteria. It is markedly increased during
      acute-phase responses. In this study, we cloned the full length of canine LBP
      cDNA and determined its amino-acid sequence and its expression in several canine
      tissues. The isolated LBP cDNA contained a 1443-bp coding region, which encodes a
      25-amino-acid signal peptide, a 456-amino-acid mature LBP and a stop codon, and a
      3'-noncoding region containing a TATTTAT motif, which is probably involved in the
      degradation and/or suppression of mRNA translation. The amino-acid sequence of
      the mature canine LBP showed 78%, 66% and 67% identity with that of human, rat
      and rabbit LBPs, respectively. In transient expression assays, canine and human
      LBPs accelerated the production of tumor necrosis factor-alpha induced by LPS in
      human monocytes. Northern blot analysis showed that LBP mRNA is mainly expressed
      in the liver and kidneys of normal dogs. In situ hybridization analysis revealed
      that the canine LBP mRNA is mainly located in hepatocytes and in epithelial cells
      of the proximal urinary tubules of the kidneys. These findings suggest that LBP
      is produced in organs readily exposed to LPS, where it probably plays an
      important role in bacterial infections, particularly in those occurring after
      major surgery.

PMID- 9565688
TI  - Six isoforms of cardiotoxin in malayan spitting cobra (Naja naja sputatrix)
      venom: cloning and characterization of cDNAs.
AB  - Cardiotoxins are the most abundant toxin components of cobra venom. Although many
      cardiotoxins have been purified and characterized by amino acid sequencing and
      other pharmacological and biochemical studies, to date only five cardiotoxin
      cDNAs from Taiwan cobra (Naja naja atra), three cDNAs from Chinese cobra (Naja
      atra) and two more of uncertain origin (either Chinese or Taiwan cobra) have been
      reported. In this paper we show the existence of four isoforms of cardiotoxin by
      protein analysis and nine cDNA sequences encoding six isoforms of cardiotoxins
      (CTX 1-3, 4a, 4b and 5) from N. n. sputatrix by cDNA cloning. This forms the
      first report on the cloning and characterization of several cardiotoxin genes
      from a single species of a spitting cobra. The cDNAs encoding these isoforms,
      obtained by reverse transcription-polymerase chain reaction (RT-PCR), were
      subsequently expressed in Escherichia coli. The native and recombinant
      cardiotoxins were first characterized by Western blotting and N-terminal protein
      sequencing. These proteins were also found to have different levels of cytolytic
      activity on cultured baby hamster kidney cells. Four of the isoforms (CTX 1, 2, 4
      and 5) are unique to N. n. sputatrix, with CTX 2 being the most abundant species
      constituting about 50% of the total cardiotoxins. The isoform CTX 3 (20%
      constitution) is highly homologous to the cardiotoxins of N. n. atra and N. n.
      naja, indicating that it may be universally present in all Naja naja subspecies.
      Our studies suggest that the most hydrophilic isoform (CTX 5) could have evolved
      first followed by the hydrophobic isoforms (CTX 1, 2, 3 and 4). We also speculate
      that Asiatic cobras could be the modern descendants of the African and Egyptian
      counterparts.

PMID- 9565689
TI  - Peroxisomal and mitochondrial carnitine acetyltransferase isozymes of the n
      alkane-assimilating yeast, Candida tropicalis, occurred by alternative initiation
      of translation from the transcripts of a single gene.
AB  - Carnitine acetyltransferase (CAT; EC 2.3.1.7) is localized in two subcellular
      organelles, peroxisomes and mitochondria, in an n-alkane-assimilating yeast,
      Candida tropicalis. The isozymes are synthesized from the first and second ATG
      codon of the open reading frame of one gene, CtCAT. Primer extension analysis and
      RNase protection assay (RPA) revealed that multiple transcription initiation
      sites were found upstream of the first ATG codon. 5' ends could not be detected
      between the first and second ATG codons. These results suggested that the
      peroxisomal CAT of C. tropicalis, initiating at the second AUG codon of the
      transcripts, was synthesized by a translational readthrough of the first AUG
      codon of the open reading frame. When CtCAT was introduced into the other yeast,
      Saccharomyces cerevisiae, 5' ends of transcripts and the protein products were
      similar to those observed in C. tropicalis. This suggested that the transcripts
      harbored sufficient information to bring about alternative initiation of
      translation in both yeasts. Using S. cerevisiae as the host cell, introduction of
      mutations into the sequence near the first AUG codon or a deletion in the region
      between the first and second AUG codons resulted in an increased ratio of
      translation from the first AUG codon, although initiation sites of transcription
      did not change. Moreover, replacing the 5' leader sequence to that of C.
      tropicalis isocitrate lyase promoter (UPR-ICL) eliminated the product initiating
      at the second AUG codon. The transcript from these cells was shorter than those
      detected from the native CtCAT-harboring cells. From these results, it was
      strongly suggested that peroxisomal and mitochondrial CAT isozymes occurred by
      the alternative initiation of translation mainly dependent on the structure and
      sequence context of the region from the 5' end to the second AUG codon, and not
      the insufficient length of the 5' leader.

PMID- 9565690
TI  - Enhancement of expression of stress proteins by agents that lower the levels of
      glutathione in cells.
AB  - The effects of diethyl maleate and buthionine sulfoximine, agents that lower
      cellular levels of glutathione, on expression of hsp27 and alphaB crystallin in
      response to stress were studied. When C6 rat glioma cells were treated with 100
      microM arsenite for 1 h, accumulation of the two proteins, estimated by specific
      immunoassays, was markedly enhanced by additional exposure to 1 mM diethyl
      maleate or 2.5 mM buthionine sulfoximine. The latter also increased heat- and
      CdCl2-induced accumulation of hsp27 and alphaB crystallin. Stress-induced
      accumulation of hsp70, estimated by Western blotting analysis, was also enhanced
      by these agents. Northern blotting analysis revealed increase in levels of mRNAs
      for hsp27, alphaB crystallin and hsp70. The period of heat shock element (HSE)
      binding activity of heat shock factor (HSF) stimulated by arsenite was extended
      by addition of diethyl maleate and buthionine sulfoximine. The induced
      phosphorylated state of HSF1 was also prolonged by diethyl maleate. Although
      exposure of cells to diethyl maleate alone for 1 h caused neither accumulation of
      hsp27, alphaB crystallin and hsp70 nor expression of mRNAs for these proteins,
      HSE-binding activity of HSF was stimulated. However, the activated HSF was not
      phosphorylated. These results suggest that diethyl maleate induces an
      intermediate state of HSF that binds to HSE but is transcriptionally inert. The
      mechanism is unclear but the levels of glutathione in cells that were exposed to
      diethyl maleate or buthionine sulfoximine were markedly decreased.

PMID- 9565691
TI  - Separation and characterization of three beta-galactosidases from Bacillus
      circulans.
AB  - Crude preparation of Bacillus circulans beta-galactosidase is known to have a
      good transglycolytic activity. Two isoforms of the enzyme have been described so
      far in the literature. Aiming at separating these two forms to assess their
      relative contribution to the regioselectivity of transglycosylation, we observed
      the presence of a third isoform never described before. This paper deals with the
      isolation procedures of the three enzymes and a re-consideration of their
      properties. The estimated molecular weight for the isoforms were 212 kDa (I), 145
      kDa (II) and 86 kDa (III), respectively. Kinetic parameters were determined
      towards the hydrolysis of o-nitrophenyl-beta-d-galactopyranoside (ONPG) and
      lactose. For ONPG the following values of Km were found: 3.6, 5.0 and 3.3 mM for
      I, II and III, respectively, whereas for lactose the values were 3.7, 2.94 and
      2.71 mM, respectively.

PMID- 9565692
TI  - Nucleotides of 18S rRNA surrounding mRNA at the decoding site of translating
      human ribosome as revealed from the cross-linking data.
AB  - mRNA analogs, 4-(N-2-chloroethyl-N-methylamino)benzylmethyl-[5'-32P]-phosphamide
      derivatives of oligoribonucleotides pAUGUn (n=0, 3 or 6), were used for affinity
      labelling of human 80S ribosomes in complexes with codon-anticodon interaction at
      the P-site. These complexes were obtained in the presence of fractionated lysate
      from rabbit reticulocytes deprived of endogenous ribosomes and mRNAs. In all
      cases, 40S subunits were labelled preferentially. Within the subunits, both
      ribosomal proteins and 18S rRNA were modified. Ribosomal proteins cross-linked to
      pAUGUn derivatives were identified earlier. In this paper, nucleotides G-1010, G
      1029, G-1033, G-1051, G-1054 and G-1059 of 18S rRNA cross-linked to both pAUG and
      pAUGU3 derivatives were identified by reverse transcription analysis.

PMID- 9565693
TI  - Adenosine 5'-tetraphosphate phosphohydrolase activity is an inherent property of
      soluble exopolyphosphatase from yeast Saccharomyces cerevisiae.
AB  - Homogeneous soluble exopolyphosphatase (EC 3.6.1.11) from yeast Saccharomyces
      cerevisiae, (scPPX1) behaves as an adenosine 5'-tetraphosphate phosphohydrolase
      (EC 3.6.1.14). The hydrolysis of adenosine 5'-tetraphosphate (p4A) to ATP and
      orthophosphate absolutely depends on one of the following cations:
      Co2+>Mn2+>Mg2+>Ni2+. Optimum pH is around 4.75 and the Km for p4A estimated at
      that pH in 50 mM sodium acetate and at 5 mM CoCl2 is 80+/-10 microM. Adenosine 5'
      pentaphosphate (p5A) is degraded under these conditions 18-fold more slowly than
      p4A. Assuming that the mass of scPPX1 is 45 kDa, the calculated kcat values for
      p4A and for p5A are 723 and 40 s-1, respectively. Two other nucleoside 5'
      tetraphosphates (p4N), guanosine tetraphosphate (p4G) and inosine tetraphosphate
      (p4I), were hydrolyzed to Pi and either GTP or ITP, respectively, at the same
      rate as that observed for the hydrolysis of p4A. Ammonium molybdate, sodium o
      vanadate and zinc chloride inhibit the hydrolysis of p4A (I50 values are 0.08,
      0.3 and 0.4 mM, respectively). This newly recognized 'acidic' adenosine
      tetraphosphatase activity from yeast is compared with two 'pH 8' adenosine
      tetraphosphatases described earlier in rabbit and yellow lupin.

PMID- 9565694
TI  - Characterization of a small chondroitin sulfate proteoglycan isolated from the
      mucus surrounding the embryos of Viviparus ater (Mollusca Gastropoda).
AB  - A small chondroitin sulfate proteoglycan was isolated and partially characterized
      for core protein and glycosaminoglycan structures from the mucus surrounding
      embryos in the developmental pouch of Viviparus ater (Mollusca Gastropoda). The
      protein bearing polysaccharide nature was confirmed by gel-permeation
      chromatography separation of fractions positive to the uronic acid dosage, 7.5%
      SDS-PAGE under reducing conditions, sequential staining with alcian blue and
      ammoniacal silver. Its molecular mass was calculated at about 228,800. After
      degradation of the galactosaminoglycan components by chondroitinase ABC in the
      presence of proteinase inhibitors, the molecular mass of the core protein was
      determined at about 72,200. Treatment of the proteoglycan with keratanase did not
      modify its electrophoretic migration. Isoelectric focusing of the core protein
      demonstrated a micro-heterogeneity with the presence of two isoforms with
      different isoelectric point, pI=8.2 and 6.6, in a ratio of about 1:2.2. The
      glycosaminoglycan component of the proteoglycan was characterized as chondroitin
      sulfate with a molecular mass of about 30,750 composed of 5% non-sulfated
      unsaturated disaccharide, 94% monosulfated disaccharides (4-monosulfated to 6
      monosulfated disaccharide ratio of 1.36) and 1. 5% disulfated disaccharides (in
      particular 1.3% 2,6-disulfated disaccharide) with a sulfate to carboxyl ratio of
      0.96. Degradation of the chondroitin sulfate with chondroitinase ABC and ACII
      permitted to determine a percentage of glucuronic acid of about 78.4. The
      proteoglycan isolated from the mucus surrounding the embryos of Viviparus ater is
      formed by a small core protein bearing about five chondroitin sulfate chains (80%
      chondroitin sulfate/20% dermatan sulfate) with potential function in the
      developmental processes of molluscs embryos.

PMID- 9565695
TI  - N-Acetyl-D-glucosamine-specific lectin from the ascidian Didemnum ternatanum.
AB  - We report the characterization of the affinity chromatography-purified N-acetyl-d
      glucosamine-specific lectin from the ascidian Didemnum ternatanum (DTL). Native
      molecular weight of lectin estimated by gel filtration was 28 000. The
      hemagglutinating activity of DTL independent of divalent cations Ca2+ and Mg2+.
      Significant activity was observed between pH 6-10. In hemagglutination inhibition
      assays among the mono- and oligosaccharides tested, N-acetyl-d-glucosamine, N, N'
      diacetylchitobiose, N,N'N"-triacetylchitotriose were the most potent inhibitors.
      They showed similar inhibitory activity. Hapten inhibition with various sugars
      indicated that DTL requires the presence of hydroxyl groups at the C-3 and C-4 of
      N-acetyl-d-glucosamine. The presence of the hydrophobic p-nitrophenyl aglycone
      significantly enhanced inhibitory power of N-acetyl-d-glucosamine. On the other
      hand among the glycoproteins ovomucoid and ovalbumin were the best inhibitors.
      The interaction of DTL with specific saccharides was investigated by UV
      difference spectroscopy and association constants were obtained. CD analysis of
      DTL suggested 4% alpha-helix, 57% beta-sheet, 24% beta-turn and 15% unorder.

PMID- 9565696
TI  - Methanopterin biosynthesis: methylation of the biosynthetic intermediates.
AB  - The basic scheme for the biosynthesis of methanopterin (MPT) in Methanobacterium
      thermoautotrophicum strain DeltaH, and M. thermoautotrophicum strain Marburg, has
      been shown to be the same as that recently determined for Methanosarcina
      thermophila strain TM-1. This scheme has, as one of its unique steps, the
      condensation of 4-aminobenzoic acid with 5-phospho-alpha-d-ribosyl diphosphate
      (PRPP) to form 4-(beta-d-ribofuranosyl)aminobenzene 5'-phosphate (beta-RFA-P).
      Labeling experiments with each of these organisms have established that the sites
      in the overall sequence of reactions from beta-RFA-P to MPT, where the S
      adenosylmethionine-dependent C-9 and C-7 methylations of the pterin-containing
      intermediates occur, are organism related. In this work, cell extracts of M.
      thermoautotrophicum strain DeltaH, and M. thermoautotrophicum strain Marburg were
      found to contain significant amounts of methanopterin lacking the phosphate and 2
      hydroxyglutaric acid groups.

PMID- 9565697
TI  - Distribution of glycoproteins with beta-N-acetylgalactosaminylated N-linked sugar
      chains among bovine tissues.
AB  - Only a small number of glycoproteins has been reported to contain N-linked sugar
      chains with GalNAcbeta1-->4GlcNAc structure. Our previous studies showed that
      most glycoproteins from bovine milk fat globule membranes contain beta-N
      acetylgalactosaminylated N-linked sugar chains [Sato et al., J. Biochem. 114
      (1993) 890-900]. In order to study how widely this glycosylation occurs, lectin
      blot analysis of membrane glycoproteins from 12 bovine tissues was performed
      using Wistaria floribunda agglutinin (WFA), which interacts with oligosaccharides
      terminating with N-acetylgalactosamine. The WFA-positive bands were detected in
      samples from most tissues except for intestine although the number and reactivity
      of bands to lectin varied among the tissues. Upon pretreatment of blotted filters
      with Bacillus beta-N-acetylgalactosaminidase or N-glycanase, no lectin binding
      was observed. WFA-agarose column chromatography of oligosaccharides released by
      hydrazinolysis from membrane glycoproteins of bovine tissues except for intestine
      revealed that a few to 18% of the released oligosaccharides bind and are eluted
      from the column with 100 mM N-acetylgalactosamine. These results indicate that
      many glycoproteins from a variety of bovine tissues contain N-linked sugar chains
      with GalNAcbeta1-->4GlcNAc structure, suggesting a wider occurrence of this
      glycosylation in bovine tissues.

PMID- 9565698
TI  - Kinetics of hydrogen peroxide elimination by human umbilical vein endothelial
      cells in culture.
AB  - H2O2 is a key substance in the oxidative stress. To evaluate the antioxidant
      activity of intact human umbilical vein endothelial cells (HUVEC), we measured
      the H2O2 removal rate by the cell in monolayer culture at various H2O2
      concentrations (1-300 microM). It was shown that the removal reaction can be
      divided into two kinetically different reactions: reaction 1 apparently following
      the Michaelis-Menten kinetics and reaction 2 following the first-order kinetics.
      Reaction 1, which was diminished by treatment with diethyl maleate, could be
      attributed to GPx. Reaction 2, which was inhibited by aminotriazole, was
      principally attributable to catalase, though non-enzymatic reactions may
      contribute to it partially. Furthermore, we have constructed a mathematical model
      for the H2O2 elimination including the pentose phosphate pathway enzymes, GSSG
      reductase and GSH peroxidase. On the basis of the known kinetics and observed
      activities of the enzymes, the model could reproduce well the observed
      concentration dependence of the H2O2 removal rate. It was suggested from the
      simulation study that GSSG reductase is more important than G6PD in determining
      the rate of the NADPH-dependent H2O2 elimination.

PMID- 9565699
TI  - Regulation of a common, low-affinity binding site for primary prostanoids on
      bovine aortic endothelial cells.
AB  - Bovine aortic endothelial cells contain a prostaglandin site which binds with
      similar low-affinity PGE2, PGF2alpha and the thromboxane agonist U-46619.
      Treatment of the cells with agents that increase the level of cellular cAMP such
      as forskolin, a direct activator of adenylate cyclase or IBMX, a
      phosphodiesterase inhibitor, decreased the binding of PGE2 to the cells. Addition
      of dibutyryl cAMP to intact cells caused a quick reduction in PGE2 binding with a
      half time of less than 2 min. The reduction in PGE2 binding was completely
      reversible after removing the dibutyryl cAMP. The reduction in PGE2 binding after
      addition of dibutyryl cAMP to the intact cells was also observed after a
      mechanical disruption of the cells or after permeabilization with digitonin.
      Incubation of the cells with myristoylated PKI(14-22) amide, a specific protein
      kinase A inhibitor, resulted in partial suppression of the reduction of PGE2
      binding by dibutyryl cAMP. Pretreatment of intact cells for 24 h with 10(-6) M
      PGE2 or a PKC activator did not reduce the specific binding of [3H]-PGE2. These
      results suggest that PKA, but not PKC, is involved in a fast reversible
      regulation of the common prostanoid receptor on bovine endothelial cells.

PMID- 9565700
TI  - The pathophysiology of brain injury: understanding innovative drug therapies.
AB  - The advancement of acute care for persons with brain injury is predicated on the
      further clarification of the mechanical and biochemical processes that are begun
      at the time of the injury. Attempts to enhance survival and functional outcome
      have led to cerebral perfusion and intracranial pressure management techniques.
      In addition, novel neuroprotective pharmacotherapeutic strategies have been borne
      from an ever growing knowledge of the degradative biochemical injury that occurs
      subsequent to the initial insult. The link between the acute and rehabilitation
      phases of care continues to grow closer, thus compelling the rehabilitationist to
      be aware of the potential effect these processes and treatments have on outcome.

PMID- 9565701
TI  - Metabolic responses and nutritional therapy in patients with severe head
      injuries.
AB  - The severe hypermetabolism and hypercatabolism seen in patients with severe head
      injuries results in malnutrition that occurs very rapidly and can cause impaired
      healing and an increased tendency to infection and multiple organ failure. Thus,
      early adequate nutritional support plays a role in functional outcome. Total
      enteral nutrition (TEN) is preferred over total parenteral nutrition (TPN), but
      TPN should be supplied promptly while increasing TEN to a goal of at least 25 to
      35 nonprotein kcal/kg/d and 2.0 to 2.5 g protein/kg/d. Nutritional formulas high
      in branched chain amino acids, glutamine, arginine, vitamins E and C, and zinc
      may also have some advantages. Growth hormone may improve anabolism.
      Hyperglycemia, especially glucose levels exceeding 200 mg/dL, must be prevented
      and/or treated promptly with insulin or decreased glucose intake. Careful
      monitoring with indirect calorimetry and nitrogen balance studies should help
      prevent inadequate protein or excessive carbohydrate intake.

PMID- 9565702
TI  - Pulmonary complications in traumatic brain injury.
AB  - Survivors of traumatic brain injury frequently develop respiratory complications
      that require specialized knowledge and management skills in both acute and
      postacute environments. This article discusses the pathophysiology of and
      treatment options for ventilatory failure, neurogenic pulmonary edema, and
      aspiration. Management of tracheostomies is also discussed, with particular
      attention paid to decision making regarding the removal of a tracheal appliance.
      Long-term tracheal complications are also outlined.

PMID- 9565703
TI  - Venous thromboembolism in the patient with acute traumatic brain injury:
      screening, diagnosis, prophylaxis, and treatment issues.
AB  - Venous thromboembolism is a life-threatening complication of traumatic brain
      injury. Consequently, knowledge of available screening, diagnostic, prophylactic,
      and treatment methods is critical to the management of the individual with
      traumatic brain injury. Venous thromboembolic risk varies among individuals,
      resulting in unique screening and prophylactic needs for each patient. In
      addition, anticoagulation, commonly employed for prophylaxis and treatment in
      other patient populations, may create an increased risk for intracranial
      hemorrhage when utilized following traumatic brain injury. The cost, sensitivity,
      specificity, efficacy, potential side effects, and alternatives for preventing,
      detecting, and treating venous thromboembolism are important considerations
      discussed in this article.

PMID- 9565704
TI  - Application of evoked potentials to the prediction of discharge status in
      minimally responsive patients: a pilot study.
AB  - Evoked potentials (EPs) have been shown to have useful prognostic value during
      the acute phase of traumatic and anoxic coma. We have hypothesized that EPs
      obtained in the subacute phase can be used to assess prognosis for functional
      recovery in minimally responsive patients with diffuse brain damage due to either
      brain trauma or anoxia. This pilot study correlated graded brainstem auditory
      evoked potentials (BAEPs) and upper extremity somatosensory evoked potentials
      (UESSEPs) with outcome grade based on the discharge Disability Rating Scale (DRS)
      score of 33 patients admitted to a responsiveness assessment program of a brain
      injury rehabilitation unit with an initial DRS score of 22 or greater. Results
      indicated a significant correlation with outcome grade for both the BAEP grade (P
      < .02) and the UESSEP grade (P < .02). The BAEP had a higher sensitivity and
      lower specificity, as false-positive exceeded false-negative predictions. The
      UESSEP tended to predict outcome more accurately and with a balanced number of
      false-positive and false-negative predictions. EPs were also found to be useful
      for detecting occult impairment of sensory function. This pilot study
      demonstrates that EPs performed near the time of admission to the rehabilitation
      unit can be useful in guiding the rehabilitation management of the minimally
      responsive patient by helping to predict functional recovery and to detect occult
      impairment of sensory systems.

PMID- 9565705
TI  - A psychodynamic model of behavior after acute central nervous system damage.
AB  - This article describes a conceptual psychodynamic model for understanding the
      neurobehavioral manifestations of acute central nervous system damage (ACNSD)
      displayed by patients during the rehabilitation process. According to the
      proposed model, patientsO behavioral responses are viewed as their only means of
      emotional expression and therefore may not be considered entirely abnormal when
      viewed from the perspective of patientsO interpersonal contexts. An improved
      understanding of the dynamic processes through which recovering patients with
      ACNSD journey may lead to better interaction between the patient and the
      therapeutic environment, the interdisciplinary team, and family members.
      Combining this proposed psychodynamic model with an emerging understanding of the
      neurobehavioral foundations of aggression and depression may also lead to a more
      rational approach to intervention with various psychopharmacologic agents. During
      the rehabilitation process, understanding patients' cognitive deficits,
      motivational drives, and emotional needs and proper implementation of medical and
      environmental treatment can ultimately lead to a better psychosocial outcome.

PMID- 9565706
TI  - A good first step toward nationwide aid to persons with brain injury: the
      Traumatic Brain Injury Act of 1996.

PMID- 9565707
TI  - Antihistamines.

PMID- 9565708
TI  - From the editor 

PMID- 9565709
TI  - Neuroimaging in patients with traumatic brain injury.

PMID- 9565710
TI  - Health services research on mental health in primary care.
AB  - OBJECTIVE: The article seeks to provide an international perspective on the
      facilitating role of health services research in the treatment of psychiatric
      disorders in primary care. It builds on Goldberg and Huxley's model describing
      pathways to mental care for the psychiatrically ill in the community. METHOD:
      Seventy studies were selected for review by Medline search, sixteen studies by
      contacting prominent researchers in the field. All studies are discussed more or
      less extensively. RESULTS: Case identification strategies including screening
      tools and diagnostic modules have been developed. Other strategies include
      educational training programs and psychiatric consultation services designed to
      facilitate psychopharmacological and other types of treatment of psychiatric
      disorders in primary care. Several models for the linkage of primary care and
      specialty mental health providers are discussed, and a primary care psychiatry
      programme is examined. CONCLUSION: Better psychiatric training of general
      practitioners (GPs), on-site consultation, and better communication between
      mental health professionals and GPs can improve the recognition, management, and
      referral of psychiatrically ill primary care patients. The further development of
      guidelines focusing on anxiety disorders, somatization, subthreshold disorders,
      and effectiveness in primary care is recommended.

PMID- 9565711
TI  - Mental health and health care utilization in geriatric primary care patients.
AB  - OBJECTIVE: This study examines the effect of mental health factors on health care
      utilization in a group of community dwelling elderly subjects followed in a
      primary care setting. METHOD: Data on utilization was obtained prospectively from
      computerized billing records for a one-year period following completion of a
      structured survey. Relationships between variables were characterized by
      Spearman's rank correlation. Multivariate linear regression modeling was employed
      to relate health care utilization, as measured by total cost, to the baseline
      variables. RESULTS: No significant relationship was found between mental health
      measures and health care utilization as measured by total costs in this elderly
      population. However, total costs were found to be related to medical comorbidity
      and total daily medication use. CONCLUSION: The present study did not find the
      relationship of psychiatric distress and increased use of health care services to
      apply to a group of community dwelling elderly. Future research will need to
      focus on larger data sets and improvement of models that attempt to examine the
      relationships between mental health and health care utilization in the elderly.

PMID- 9565712
TI  - Perceived mental health and disablement of primary care and end-stage renal
      disease patients.
AB  - OBJECTIVE: To compare perceived current mental health and disablement between
      primary care and end-stage renal disease (ESRD) patients, and to study social
      support and stress and severity of illness as possible determinants of mental
      health and disablement. METHOD: Observational cross-sectional analysis of 414
      primary care patients in a rural community health center and 125 ESRD patients
      requiring hemodialysis in two community dialysis units. The Duke Health Profile
      (DUKE) anxiety-depression scale was used to assess mental health; the DUKE
      disability scale, to indicate disablement; the Duke Social Support and Stress
      Scale, to measure support and stress; and the Duke Severity of Illness Scale, to
      rate severity of illness. RESULTS: Perceived current mental health in terms of
      anxiety and depression symptoms was worse for primary care than for ESRD
      patients, and perceived current disablement was no different for the two groups.
      Patients' perception of their health status and of stress from family members
      were more closely associated with their level of anxiety and depression symptoms
      than were their diagnostic profiles or overall severity of illness. In turn,
      their level of anxiety and depression symptoms was the principal correlate of
      their disablement. CONCLUSIONS: The demonstration of strong relationships among
      anxiety and depression symptoms, disablement, and family stress in these two very
      different patient populations should stimulate further research and motivate
      clinicians to evaluate all three parameters as part of routine patient care.

PMID- 9565713
TI  - Self-reported allergy-related symptoms and psychological morbidity in primary
      care.
AB  - OBJECTIVE: To examine the relationship between allergy-related symptoms, food
      intolerance and psychological distress in primary care. METHODS: Two thousand
      three hundred and thirty two adults in five General Practices in the South of
      England completed questionnaires regarding allergy-related symptoms and
      psychological symptoms, but no association was demonstrated between a history of
      diagnosed or treated asthma, eczema or hay fever and psychological morbidity.
      Cases of food intolerance had lower levels of psychological distress than
      expected compared to hospital samples. Current, but not past wheezing and eczema,
      was associated with an excess of life stresses in the previous six months.
      CONCLUSIONS: The association between psychological distress and the label of food
      allergy/intolerance found in specialist care does not extend to primary care.

PMID- 9565714
TI  - Anxiety and depression in patients receiving implanted cardioverter
      defibrillators: a longitudinal investigation.
AB  - OBJECTIVE: The implantable cardioverter-defibrillator (ICD) has dramatically
      improved survival rates following sudden cardiac death episodes. However,
      researchers have devoted little attention to the psychosocial consequences of
      living with the device. The current study used a longitudinal design to evaluate
      the impact of adaptation to the ICD on incidence and severity of anxiety and
      depression. METHOD: ICD recipients were administered standardized anxiety and
      depression questionnaires as well as questions evaluating quality of life related
      to the ICD in two consecutive yearly assessments. A preliminary evaluation of
      potentially important theoretical variables, such as the perceived predictability
      and controllability of shock onset was also conducted. RESULTS: One-third of the
      study population (N = 38) had clinically significant levels of anxiety, depressed
      mood, and fear of symptoms of autonomic arousal. These negative affective states
      persisted over time, with 40 to 63 percent of subjects continuing to have ongoing
      difficulties over a one-year time period. Anxiety about the ICD firing was
      closely associated with the occurrence of depression, while avoidance of
      activities was associated with anxiety. "Worry" about the ICD and a belief that
      ICD firing can be predicted were associated with anxiety sensitivity.
      CONCLUSIONS: Depressive and anxiety states in ICD recipients may be frequent,
      clinically significant, and resistant to spontaneous resolution. Early signs of
      anxiety and depression in ICD recipients should be evaluated. Implications for
      future research are discussed.

PMID- 9565715
TI  - Fluoxetine in depressed patients on dialysis.
AB  - OBJECTIVE: To test the safety and efficacy of fluoxetine in patients with renal
      failure on dialysis. METHOD: Fourteen patients with major depression and end
      stage renal disease on hemodialysis were randomized into two groups for an eight
      week study. Subjects as well as investigators were blinded as to which subject
      received fluoxetine and which placebo. Patients were carefully monitored
      concerning adverse events, serum fluoxetine and norfluoxetine levels, and
      psychological measurements of degree of depression. RESULTS: No patients
      discontinued treatment because of adverse events, all of which were minor. All
      psychological tests showed improvement in depression at the four-week and eight
      weeks point, although statistical significance could only be demonstrated at the
      fourth week of this study. All patients in the active group had serum plasma
      concentrations of fluoxetine and norfluoxetine less than 250 ng/ml at eight
      weeks, similar to levels in patients with normal renal function in a previous
      open label study. CONCLUSIONS: This study confirms the relative safety of
      fluoxetine in depressed patients in renal failure on hemodialysis. It also
      suggests that fluoxetine may be efficacious in depressed patients on dialysis.

PMID- 9565716
TI  - Serotonin reuptake inhibitors and the adequacy of antidepressant treatment.
AB  - OBJECTIVE: To determine whether the use of serotonin reuptake inhibitors (SSRIs)
      improves antidepressant medication prescribing patterns for both psychiatric and
      non-psychiatric physicians. DATA SOURCES/SETTING: Drug utilization review of
      4,103 prescriptions for antidepressant medications with patients diagnosed with
      depressive disorders over an eighteen-month period from the formulary records of
      a large insurance company. DESIGN: Using standards developed for clinical
      guidelines, variation in trial and treatment adequacy between drug types and
      physician specialty was studied. PRINCIPAL FINDINGS: Thirty-five percent of
      initial antidepressant trials were not prescribed for an adequate duration or at
      an adequate dosage level. SSRIs were more likely to be prescribed adequately than
      any other antidepressant reviewed. Psychiatrists were more likely to prescribe
      antidepressants at an adequate dosage level, whereas non-psychiatric physicians
      were more likely to attain adequate duration of treatment. CONCLUSIONS: A greater
      reliance on SSRIs may increase the likelihood of maintaining adequacy in
      antidepressant treatments. Although higher in cost than other treatment choices,
      their lower side effect profile is likely to maximize patient satisfaction and
      physician and patient adherence to guidelines. In order to ensure effective and
      efficient antidepressant usage, such patterns must be identified and appropriate
      performance improvement strategies (e.g., Total Quality Improvement, critical
      pathways) may be employed.

PMID- 9565717
TI  - Assessing psychiatric impairment in primary care with the Sheehan Disability
      Scale.
AB  - OBJECTIVE: Several recent studies have documented that substantial functional
      impairment is associated with many of the mental disorders seen in primary care.
      However, brief measures of mental health-related functional impairment are not
      commonly applied in primary care settings. The Sheehan Disability Scale (SDS), a
      three-item instrument for assessing such impairment, is evaluated in this study.
      METHOD: A psychometric analysis of the SDS was conducted with a sample of 1001
      primary care patients at Kaiser Permanente In Oakland, California. The SDS and
      the Symptom Driven Diagnostic System for Primary Care assessments were completed.
      RESULTS: The internal consistency reliability of the SDS is high, with
      coefficient alpha of 0.89. The construct validity was substantiated in two ways.
      A one-factor model fit the data quite well. Furthermore, patients with each of
      six psychiatric disorders had significantly higher impairment scores than those
      who did not. Finally, over 80 percent of the patients with mental disorder
      diagnoses had an elevated SDS score and nearly 50 percent of those with elevated
      SDS scores had at least one disorder. CONCLUSIONS: The psychometric properties of
      the SDS were evaluated in primary care. The internal consistency reliability was
      high. The analyses also lend empirical support for the construct validity. The
      scale is a sensitive tool for identifying primary care patients with mental
      health-related functional impairment, who would warrant a diagnostically-oriented
      mental health assessment.

PMID- 9565718
TI  - PRIME-MD: its utility in detecting mental disorders in American Indians.
AB  - OBJECTIVE: To examine the utility of using PRIME-MD (Primary Care Evaluation of
      Mental Disorders) for diagnosing mental disorders in American Indians. METHOD:
      One hundred randomly selected, adult, American-Indian patients who receive health
      care services at an urban Indian Health Service primary care clinic were
      evaluated for mental disorder by three primary care physicians using the PRIME-MD
      diagnostic assessment procedure. The main outcome measures were PRIME-MD
      diagnoses, diagnoses by an independent mental health professional, and
      treatment/referral decisions. RESULTS: Eighteen percent of the patients had a
      threshold (met full DSM-IV criteria ) PRIME-MD diagnosis, and an additional 17
      percent had a subthreshold PRIME-MD diagnosis. The most frequently occurring
      PRIME-MD diagnoses were: probable alcohol abuse/dependence, major depressive
      disorder, and generalized anxiety disorder. Over 60 percent of the patients with
      a PRIME-MD diagnosis who were known "somewhat" or "fairly well" to their
      physician had not been recognized as having that psychiatric disorder prior to
      the PRIME-MD assessment. Therapy and/or referral was initiated for nineteen of
      the twenty-seven patients with a PRIME-MD diagnosis who were not previously
      receiving treatment. The primary care physicians were able to complete the PRIME
      MD evaluations within an average of 7.8 minutes. There was a fair agreement
      between the PRIME-MD diagnoses and the diagnoses of the mental health
      professional (kappa = 0.56; overall accuracy rate = 79%). CONCLUSIONS: The
      present study represents the first formal examination of the use of PRIME-MD with
      American Indians. The results are encouraging. Further studies using PRIME-MD
      with other urban groups and reservation populations are recommended.

PMID- 9565719
TI  - Sociodemographic predictors of response to antidepressant treatment.
AB  - OBJECTIVE: Our goal was to assess whether sociodemographic variables such as
      gender, marital status, level of education, and employment status are related to
      the changes in social functioning that have been reported after drug treatment in
      outpatients with major depressive disorder. METHOD: Eligible subjects were 166
      depressed outpatients participating in a study involving open treatment with
      fluoxetine 20 mg/day for eight weeks. Diagnosis of major depressive disorder was
      made with the use of the Structured Clinical Interview for DSM-III-R-Patient
      Edition (SCID-P), and patients were required to have a seventeen-item Hamilton
      Rating Scale for Depression (HAM-D-17) score > or = at study entry. All subjects
      were administered the HAM-d-17 and the Social Adjustment Scale-Self-Report (SAS
      SR) before and after treatment with fluoxetine. RESULTS: We found that SAS-SR
      scores decreased significantly following treatment with fluoxetine from a mean
      score at baseline of 2.6 +/- 0.7 to a mean score at endpoint of 2.3 +/- 0.6.
      After adjusting for the degree of change in HAM-D-17 scores, we found a
      significant relationship between degree of change in SAS-SR and level of
      education. No statistically significant relationships were observed between SAS
      SR change and age, gender, marital status, and employment status. CONCLUSION: The
      degree of improvement in psychosocial functioning observed in depressed
      outpatients following antidepressant treatment appears to be related to the level
      of education at study entry, but not to other sociodemographic variables. Further
      studies need to investigate the nature of this relationship.

PMID- 9565720
TI  - Vegetative and psychological symptoms associated with depressed mood over the
      first two years after stroke.
AB  - INTRODUCTION: In patients with acute physical illness, symptoms used in the
      diagnosis of major depression such as sleep or appetite disturbance may be
      nonspecific for depression. This study was undertaken to examine the association
      of depressed mood with other depressive symptoms to determine which symptoms were
      most useful in the accurate diagnosis of major depression after stroke. METHODS:
      Using a structured mental status examination, 142 patients with acute stroke were
      followed at three, six, twelve, and twenty-four months. RESULTS: The median
      number of vegetative and psychological symptoms among patients with depressed
      mood was more than three times the respective rates among nondepressed patients
      at all time points over two years. Autonomic anxiety, morning depression,
      subjective anergia, worrying, brooding, loss of interest, hopelessness, and lack
      of self-confidence were significantly more frequent among depressed patients than
      nondepressed patients throughout the entire two-year period. Some symptoms such
      as anxious foreboding and loss of libido, as well as self-depreciation, feelings
      of guilt, and irritability were no longer significantly more common among
      depressed compared with nondepressed patients after six months. Standard DSM-IV
      diagnostic criteria and modified DSM-IV diagnostic criteria which included only
      specific symptoms of depression (i.e., symptoms which were significantly more
      frequent among depressed than nondepressed mood patients) yielded similar
      frequencies of major depression diagnosis. There were only a few patients (i.e.,
      2% to 3%) with depressive symptoms without a depressed mood (perhaps "masked"
      depression). CONCLUSIONS: Vegetative and psychological depressive symptoms are
      significantly more common in depressed patients over the first two years after
      stroke and DSM-IV criteria do not overdiagnose major depression even in this
      population with chronic physical illness. The symptoms which characterize major
      depression appear to change between the subacute and chronic post-stroke periods.

PMID- 9565721
TI  - Psychological distress in HIV-1 disease in relationship to hypocholesterolemia.
AB  - OBJECTIVE: Altered levels of serum cholesterol, which are prevalent in early HIV
      1 infection, have been associated with disturbances in mood state and behavior.
      The objective of this study was to evaluate the relationship of serum cholesterol
      status and psychological distress in HIV-1 seropositive and seronegative men.
      METHOD: The association between serum cholesterol level and psychological
      distress, measured with the Profile of Mood States (POMS), was examined in 169
      individuals (117 HIV-1 seropositive and 52 seronegative homosexual men),
      controlling for negative life events, social support, coping style, and HIV-1
      serostatus. RESULTS: Individuals with hypocholesterolemia (serum cholesterol
      levels < 150 mg/dL), exhibited significantly higher levels of distress, relative
      to individuals with values of cholesterol > 150 mg/dL (p = 0.01). HIV-1
      seropositive men had significantly lower cholesterol levels (p = 0.0001) and
      higher levels of distress than the seronegative men (p = 0.03). A significant
      interaction between negative life events and cholesterol status was demonstrated
      as well (p = 0.04). CONCLUSIONS: Hypocholesterolemia appears to be associated
      with increased psychological distress. Whereas the causal direction of the
      cholesterol-distress association cannot be specified, our results suggest that
      HIV-1 infected men with low cholesterol levels may benefit from being monitored
      for changes in distress level, so that appropriate psychosocial intervention can
      be instituted, as necessary.

PMID- 9565722
TI  - Reassurance therapy: what to say to symptomatic patients with benign or non
      existent medical disease.
AB  - Reassurance is one of the most important therapies that primary care physicians
      give; however, little has been written about it in the literature. This article
      suggests six steps needed for effective reassurance in patients with benign
      disease or symptoms not explained by disease. These include; 1) question and
      examine the patient, 2) assure the patient that serious illness is not present,
      3) suggest the symptom will resolve, 4) tell the patient to return to normal
      activity, 5) consider non-specific treatment, and 6) follow the patient Only if
      these systematic steps are followed will reassurance consistently work. Since
      examination of the patient is a critical component of reassurance therapy, it can
      most effectively be administered by individuals who include a physical assessment
      as a part of the clinical evaluation.

PMID- 9565723
TI  - The 'research magnificent' in late life: psychiatric epidemiology and the primary
      health care of older adults.
AB  - OBJECTIVE: Primary care occupies a strategic positive in the evaluation,
      treatment, and prevention of the mental disturbances of later life. This article
      highlights four themes that are crucial to understanding mental disturbances
      among older adults: 1) subsyndromal depression, 2) coexisting depression and
      anxiety, 3) comorbidity of depression and chronic medical conditions, and 4) risk
      factors for cognitive impairment. METHOD: The literature was selectively reviewed
      for each theme to ask the central question, "What can primary care physicians
      learn about mental disturbances of their older patients from epidemiologic and
      community studies?" RESULTS: The primary care setting itself is an important
      venue for an examination of aging issues and mental health. Workers in the
      "middle ground of psychiatric epidemiology"--primary health care--have not yet
      reached a full appreciation for the value of research in the primary care setting
      for enhancing our understanding of the mental disturbances of late life, and how
      these intersect with other salient factors. CONCLUSIONS: Primary care physicians
      and others who work in primary care should advocate for further mental health
      integration and research in primary care. Research is needed that will lead to
      new ways of maximizing the health and quality of life of older adults and their
      families.

PMID- 9565724
TI  - Psychogeriatrics and general practice in Australia.
AB  - We describe the interface between general practice and psychogeriatrics in
      Australia. While aged care services are complex and there are serious
      deficiencies in the management of the elderly, several initiatives appear set to
      improve the level of care. Economic considerations, mutual education of general
      practitioners and psychogeriatricians, and social factors are strong determinants
      of good primary care of the mental health needs of older people.

PMID- 9565725
TI  - Treatment of depression in older primary care patients in health maintenance
      organizations.
AB  - OBJECTIVE: To examine whether older HMO patients with depression are treated
      differently than younger patients in terms of diagnosis, treatment by specialty
      provider, and pharmacotherapy. DESIGN: Chart-review, Cross sectional study.
      SETTING AND PARTICIPANTS: Patients were selected from six HMOs in the United
      States who had one or more of five medical diagnoses: arthritis, asthma, otitis
      media, epigastric pain/ulcer, and hypertension, (n = 9143). From this group,
      chart diagnoses and pharmacy records were used to identify patients who also had
      a diagnosis of depression (n = 416) or who had a diagnosis of depression and/or
      treatment with antidepressant medication (n = 1286). MEASUREMENT: Medical records
      and computerized service and pharmacy records were reviewed to obtain diagnoses,
      office visits by provider type, and psychiatric medication prescription counts.
      RESULTS: Significant differences were found in treatment of depression for older
      versus younger patients. Although depression was identified at a similar rate for
      both groups, older patients received fewer mental health specialty visits and
      fewer prescriptions for SSRI antidepressants. Older patients with a diagnosis of
      depression were more likely to be treated with benzodiazepines (49.2% of older
      vs. 33.2% of younger) though they were less likely to receive long half-life
      benzodiazepines. CONCLUSIONS: Psychotropic medication management is an important
      target for improving quality of care for older patients with depression in HMOs.
      Decreasing inefficient minor tranquilizer use and increasing use of newer
      antidepressant medications may lead to improved outcomes for older depressed
      adults.

PMID- 9565726
TI  - Attendance at religious services, interleukin-6, and other biological parameters
      of immune function in older adults.
AB  - OBJECTIVE: First, to examine and explain the relationship between religious
      service attendance and plasma Interleukin-6 (IL-6) levels, and second, to examine
      the relationship between religious attendance and other immune-system regulators
      and inflammatory substances. METHODS: During the third in-person interview (1992)
      of the Establishment of Populations for Epidemiologic Studies of the Elderly
      (EPESE) project, Duke site, 1718 subjects age sixty-five or over had blood drawn
      for analysis of immune regulators and inflammatory factors, including IL-6
      measurements. IL-6 was examined both as a continuous variable and at a cutoff of
      5 pg/ml. Information on attendance at religious services was available from the
      1992 interview and two prior interviews (1986 and 1989). RESULTS: Religious
      attendance was inversely related to high IL-6 levels (> 5 pg/ml), but not to IL-6
      measured as a continuous variable. Bivariate analyses revealed that high
      religious attendance in 1989 predicted a lower proportion of subjects with high
      IL-6 in 1992 (beta-.10, p = .01) High religious attendance in 1992 also predicted
      a lower proportion of subjects with high IL-6 levels in 1992 (beta-.14, p =
      .0005). When age, sex, race, education, chronic illnesses, and physical
      functioning were controlled, 1989 religious attendance weakened as a predictor of
      high IL-6 (beta-.07, p = .10), but 1992 religious attendance retained its effect
      (beta-.10, p = .02). When religious attenders were compared to non- attenders,
      they were only about one-half as likely to have IL-6 levels greater than 5 ng/ml
      (OR 0.58, 95% CI 0.40-0.84, p < .005). Religious attendance was also related to
      lower levels of the immune-inflammatory markers alpha-2 globulin, fibrin d
      dimers, polymorphonuclear leukocytes, and lymphocytes. While controlling for
      covariates weakened most of these relationships, adjusting analyses for
      depression and negative life events had little effect. CONCLUSIONS: There is a
      weak relationship between religious attendance and high IL-6 levels that could
      not be explained by other covariates, depression, or negative life events. This
      finding provides some support for the hypothesis that older adults who frequently
      attend religious services have healthier immune systems, although mechanism of
      effect remains unknown.

PMID- 9565727
TI  - Deciphering the physician-older patient interaction.
AB  - OBJECTIVE: The purpose of this article is to provide a commentary on non-verbal
      communication in the physician-older patient interaction. METHOD: A literature
      review of physician-older patient communication yielded several published studies
      on this topic. Nonverbal behaviors were rarely examined in this body of
      literature even though the need to adopt a more "biopsychosocial" model of care
      was mentioned in several of the articles. The nonverbal communication literature
      was also reviewed to determine whether aging had been a variable of interest with
      regard to encoding (sending) and decoding communication (receiving) skills.
      RESULTS: To date there have been very few studies that have investigated the role
      of nonverbal communication in the physician-older patient interaction. Selected
      encoding and decoding characteristics for both physicians and patients are
      discussed with the context of the aging process. In lieu of direct evidence
      linking nonverbal behavior and physician-older patient communication, possible
      implications are offered for the following characteristics: expression of
      emotion, pain expression, gestures, gaze, touch, hearing, and vocal affect. Three
      relevant outcomes (satisfaction with care, quality of life, and health status)
      are also discussed within the nonverbal behavior-aging framework. CONCLUSION: The
      connection between nonverbal behavior and how physicians and older patients
      interact with one another has not been rigorously examined. Identifying and
      improving nonverbal communication will likely enhance the verbal exchange in the
      medical encounter and may improve the older patient's quality of care.

PMID- 9565728
TI  - Diagnosis and management of late life depression: a guide for the primary care
      physician.
AB  - OBJECTIVE: The purpose of this article is to provide a brief and practical
      approach for the primary care physician regarding the recognition, diagnosis, and
      management of depression in elderly patients. METHOD: Empirical evidence and
      current recommendations regarding the recognition, diagnosis, and treatment of
      depression are reviewed as the basis for this approach. Appropriate modifications
      for geriatric depression are added where indicated. RESULTS: The recommendations
      are listed by category and briefly explained. CONCLUSIONS: It is important to be
      vigilant for the variety of depressive presentations that occur in older primary
      care patients. Neurological causes of depression (such as stroke), suicide, and a
      longer time to recovery are all more frequent concerns in older depressed
      patients.

PMID- 9565729
TI  - Evidence based health care in old age psychiatry.
AB  - OBJECTIVE: The purpose of this article is to present the current status and
      future needs of old age psychiatry in relation to evidence-based health care.
      METHOD: The opportunities and difficulties of evidence-based medicine as applied
      to old age psychiatry are described. Depression is used as a specific example.
      The role of the Cochrane Collaboration and of clinical guidelines in dealing with
      these difficulties are discussed. RESULTS: There has been a tendency for drug
      studies to focus on younger age groups and to exclude patients with comorbidity
      or polypharmacy. Aspects of clinical management separate from drugs are given
      insufficient attention. The generalizability of current studies is a problem in
      old age psychiatry. CONCLUSIONS: Psychiatry is no less part of medicine than any
      other specialty. Increased attention to studies of effectiveness, as opposed to
      efficacy, is indicated. The Cochrane Collaboration is an international network
      which promotes and conducts systematic reviews of the effectiveness of health
      care. Systematic reviews can increase the generalizability of the current
      knowledge base and better define the needs for future research.

PMID- 9565730
TI  - Addressing Murphy's law in health care policy: a responsibility for physicians.

PMID- 9565731
TI  - Antidepressant efficacy and cardiovascular safety of venlafaxine in young vs old
      patients with comorbid medical disorders.
AB  - OBJECTIVE: To determine whether venlafaxine exerts a differential effect on blood
      pressure in young versus old depressed patients. METHOD: We compared thirty-four
      consecutive patients treated with 50-250 mg/day venlafaxine for major depressive
      disorder or another major mood disorder at our medical college's ambulatory
      neuropsychiatry program. We obtained baseline and follow-up blood pressure
      measurements. Each patient also received a baseline and final Clinical Global
      Impressions (CGI) score; global improvement was determined by consensus of two
      clinicians. RESULTS: Sixteen nongeriatric patients (age, 13 to 56 years) were
      compared with eighteen elderly patients (age, 65 to 86 years). Most patients
      (88%) had serious medical comorbidities or histories. Despite a higher mean daily
      venlafaxine dosage for patients in the young group, no significant changes in
      systolic blood pressure were noted in either group. For the older group, we found
      a non-statistically significant 4.7 mm Hg mean increase in diastolic blood
      pressure. No patient became hypertensive. We also found a negative correlation
      between baseline diastolic blood pressure and change in diastolic blood pressure
      during treatment with venlafaxine. This inverse relationship was statistically
      significant in the older patients. CONCLUSIONS: Venlafaxine was not associated
      with significant, sustained changes in blood pressure in any patient receiving
      dosages of 50-250 mg/day. Minimal changes in diastolic blood pressure were no
      more likely to occur in older venlafaxine-treated patients than in younger ones.
      Higher baseline diastolic blood pressure in older patients, but not in younger
      ones, seemed to protect against diastolic adrenergic blood pressure effects of
      venlafaxine.

PMID- 9565732
TI  - Religious coping in the nursing home: a biopsychosocial model.
AB  - OBJECTIVE: To examine psychosocial and physical health correlates of religious
      coping in medically ill chronically institutionalized older adults. Religious
      coping is defined as the extent to which persons use religious beliefs and
      practices to help them to cope. METHOD: This is a cross-sectional cohort study
      conducted in a 120 bed VA-affiliated and a 125 bed university affiliated
      community-based nursing home in Durham, North Carolina. Participants were 115
      chronic care nursing home residents; mean age of the sample was seventy-nine
      years, 44 percent were women, and 17 percent were African Americans. Subjects
      were enrolled for a one-month period during which comprehensive psychosocial and
      health assessments were performed, including evaluation of cognitive function
      (Mini-Mental State Exam), physical function (Barthel index), severity of medical
      comorbidity (Cumulative Illness Rating Scale), self-reported physical pain
      (vertical verbal descriptor scale), depressive symptoms (Geriatric Depression
      Scale), social support (social network), and religious coping (Religious Coping
      Index). RESULTS: Over 43 percent of the sample scored in the depressed range of
      the Geriatric Depression Scale. Almost 60 percent reported they used religion at
      least to a large extent when coping with their problems; 34 percent said that it
      was the most important factor that enabled them to cope. Patients who used
      religion to cope had greater social support (p = .01), more severe medical
      illness (p = .04), and better cognitive functioning (p = .02). CONCLUSIONS:
      Religious beliefs and practices are frequently used by chronically
      institutionalized older adults to help them to cope. Religious coping is
      associated with more severe medical illness, higher social support, and better
      cognitive functioning.

PMID- 9565733
TI  - Cost-benefit & cost-effectiveness analysis of the rapid onset of selective
      serotonin reuptake inhibitors by augmentation.
AB  - OBJECTIVE: This article describes a method for evaluating the value of the
      increased cost of pharmacologic augmentation of an antidepressant. METHOD: Data
      to illustrate the method and interpretation of results were derived from a
      randomized, placebo controlled double blind trial. Eighty outpatients meeting ICD
      10 criteria for depressive disorder and scoring > 18 on the Montgomery Asberg
      Depression Rating Scale (MADRS) were recruited from a primary care population.
      All patients received SSRI antidepressant and either "augmenting agent" or
      placebo. The trial period was six weeks, during which the patients were monitored
      for changes in depressive symptoms using the MADRS. The economic analysis is
      based only on direct costs of treatment. The analytic approach includes decision
      analysis, cost-effectiveness and cost-benefit techniques, and a sensitivity
      analysis. RESULTS: The economic analysis was performed on both the intention-to
      treat and per-protocol population. Intention-to-treat and per-protocol results
      show that the direct cost of six weeks' treatment with the combination of
      "augmenting agent" and SSRI antidepressant, if the acceleration effect is taken
      into account, was more cost effective than the SSRI antidepressant and placebo.
      CONCLUSION: The direct costs of treatment are higher than those of previous
      pharmaco-economic studies, but the rate of onset of antidepressant action must be
      taken into account. The application of the evaluative model appears valid and
      useful. The model is pragmatic and should be expanded for generalizability.

PMID- 9565734
TI  - Reference to psychiatric consultation in the discharge letter of general hospital
      inpatients.
AB  - OBJECTIVE: The consultation-liaison psychiatrist is frequently confronted with
      the consultees' lack of adherence to the consultants' recommendations. The aim of
      this study was to investigate the question if and how the C-L psychiatrist's
      diagnoses and recommendations are mentioned in the consultee's final medical
      report and thus communicated to the physician responsible for the aftercare.
      METHOD: Psychiatric consult reports of a consecutive sample of 144 patients of
      the departments of neurology, internal medicine, and gynecology and obstetrics at
      the University Hospital of Zurich were compared to the content of the respective
      discharge letters. RESULTS: Some kind of information about the psychiatric
      consultation was found in 84 percent of the discharge letters (consultation as
      such: 71.5%; psychiatric diagnosis: 66.7%; recommendations: 76.2%. Length of
      stay, timing of the consultation, length of the consult report and type of
      recommendation correlated significantly with the mention of psychiatric aspects
      in the final medical report. Psychotropic medication and psychiatric
      hospitalization were the recommendations most reliably mentioned. CONCLUSIONS:
      Psychiatric consultation seems to be taken seriously by attending physicians and
      is communicated in a high percentage to the physicians responsible for the
      aftercare. Nevertheless, in patients where active post-discharge management is
      needed the C-L psychiatrist should actively manage referral to outpatient
      settings and/or instruct primary care providers.

PMID- 9565735
TI  - Risperidone in the treatment of delusions of infestation.
AB  - OBJECTIVE: The aim of this study is to describe the efficacy and safety of
      risperidone, in the treatment of delusions of infestation. METHOD: The authors
      present a three-case series in which risperidone was used to treat delusions of
      infestation. RESULTS: All three patients responded to risperidone and experienced
      no extrapyramidal side effects. Two of our patients had failed treatment with
      haloperidol and another had failed treatment with pimozide. CONCLUSION:
      Risperidone was an effective and safe treatment in three cases of delusions of
      infestation. It is possible that 5-HT2 antagonism is essential for therapeutic
      benefit in this condition.

PMID- 9565738
TI  - Retinoic acid syndrome. Recognition, prevention and management.
AB  - The introduction of treatment with tretinoin (all-trans retinoic acid) and its
      combination with antineoplastic therapy has improved the outcome of acute
      promyelocytic leukaemia (APL). Retinoic acid syndrome is the major adverse effect
      of tretinoin and it occurs in about 25% of treated APL patients in the absence of
      prophylactic measures and is often fatal. Generally, the retinoic acid syndrome
      is associated with increasing leucocyte counts and is probably caused by the
      release of several cytokines by maturing blast cells. The retinoic acid syndrome
      gives a clinical picture of bodyweight gain, respiratory distress, serous
      effusions and cardiac and renal failure. Adequate prophylaxis, based on the
      addition to tretinoin of dexamethasone and also, according to most authors,
      antineoplastic therapy (in case of rapidly increasing leucocyte counts) has
      decreased the incidence of retinoic acid syndrome to about 15%. Most importantly,
      these measures have reduced its mortality to about 1% of all treated patients.

PMID- 9565737
TI  - Drug interactions with grapefruit juice. Extent, probable mechanism and clinical
      relevance.
AB  - Concomitant intake with grapefruit juice increases the concentrations of many
      drugs in humans. The effect seems to be mediated mainly by suppression of the
      cytochrome P450 enzyme CYP3A4 in the small intestine wall. This results in a
      diminished first pass metabolism with higher bioavailability and increased
      maximal plasma concentrations of substrates of this enzyme. The effect was most
      pronounced in drugs with a high first pass degradation and in many cases has the
      clear potential to reach clinical relevance, as shown by an occasional change in
      drug effects or tolerability. For felodipine, nitrendipine, nisoldipine and
      saquinavir, the interaction was most marked with median increases of area under
      the curve (AUC) and/or the maximum (peak) plasma drug concentration after single
      dose administration (Cmax) values exceeding 70% of respective control periods.
      Less pronounced, but possibly relevant, concentration increases were found for
      nifedipine, nimodipine, verapamil, cyclosporin, midazolam, triazolam and
      terfenadine. This list is not complete because many drugs have not been studied
      yet. The components of grapefruit juice which are the most probable causes of the
      interactions are psoralen derivatives, but the flavonoid naringenin may also
      contribute. Concomitant grapefruit juice intake does not generally decrease the
      variability of drug pharmacokinetic parameters. Therefore, it is recommended that
      patients refrain from drinking grapefruit juice when they are taking a drug that
      is extensively metabolised, unless a lack of interaction has already been
      demonstrated for the drug. It is also recommended that drugs possibly interacting
      with grapefruit juice should be appropriately labelled. A place for grapefruit
      juice as a drug-sparing agent in treatment involving expensive medicine cannot be
      derived from the information currently available on grapefruit juice
      interactions.

PMID- 9565739
TI  - Safety review of adult clinical trial experience with lamotrigine.
AB  - To date approximately 4000 adults > 12 years of age have been treated with
      lamotrigine in Glaxo Wellcome sponsored clinical trials. Review of the data from
      these trials shows lamotrigine to be effective and well tolerated in both add-on
      and monotherapy treatment. Safety of lamotrigine was comparable to that of other
      anticonvulsants in add-on controlled clinical trials. In addition, fewer than
      half the number of patients in monotherapy studies who were taking lamotrigine
      discontinued treatment because of adverse events compared to those taking
      carbamazepine and phenytoin. Most of the reported adverse events seen in
      lamotrigine treated patients in all studies were judged by the investigator to be
      mild or moderate in severity; few of the adverse events resulted in the
      withdrawal of patients from studies. Analysis of vital signs and clinical
      laboratory data have revealed no undesirable effect of lamotrigine on major
      systems of the body. The most concerning adverse event has been rash. In clinical
      trials, this has most often been limited to a simple morbilliform rash which is
      not associated with evidence of systemic involvement. The incidence of Stevens
      Johnson syndrome (SJS) in clinical trials is approximately 1 in 1000. Rash
      associated with lamotrigine has typically occurred within the first 8 weeks of
      treatment. Data from clinical trials clearly point to exceeding currently
      recommended dosage guidelines of lamotrigine and co-administration of valproic
      acid (valproate sodium) as risk factors for rash. Early in 1997, Glaxo Wellcome
      strengthened existing warnings in the product label regarding the risk of rash
      and reinforced the importance of adherence to administration guidelines in an
      effort to reduce the incidence of rash.

PMID- 9565740
TI  - A meta-analysis to assess the incidence of adverse effects associated with the
      transdermal nicotine patch.
AB  - To estimate the frequency of adverse effects associated with the use of the
      transdermal nicotine patch, we abstracted and analysed data from 47 reports of 35
      clinical trials. The meta-analysis presented here represents a synthesis of data
      from 41 groups of nicotine patch recipients totalling 5501 patients, and 33
      groups of placebo recipients totalling 3752 patients. Smoking abstinence was the
      primary outcome in 32 of the trials, and relief of colitis symptoms was the
      primary outcome in 2 of the trials; 1 study of contact sensitisation was included
      in the skin irritation analysis. The patch was clearly effective as an aid to
      smoking abstinence. Despite the large number of patients in the analysis, few
      adverse cardiovascular outcomes (myocardial infarction, stroke, tachycardia,
      arrhythmia, angina) were reported, and no excess of these outcomes was detected
      among patients assigned to nicotine-patch use. The incidences of several minor
      adverse effects were clearly elevated among the nicotine-patch groups, especially
      sleep disturbances, nausea or vomiting, localised skin irritation and respiratory
      symptoms, but the background rates and risk ratios varied considerably across
      studies. The incidence of nausea or vomiting appeared to be lowest when the patch
      dose was tapered. The results of this meta-analysis indicate that very large
      studies would be needed to assess the effect of the patch, if any, on serious,
      rare outcomes. These results also suggest that the rate of minor adverse effects
      might be lowered by modifying patch-use protocols.

PMID- 9565741
TI  - Treatment with growth hormone and insulin-like growth factor-1 in septicemia:
      effects on carbohydrate metabolism.
AB  - Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may be beneficial
      against the protein catabolism seen in injury and septicemia. Further
      understanding of their effects on carbohydrate metabolism is needed. In a septic
      porcine model receiving total parenteral nutrition, pretreatment with GH or IGF-1
      (or no treatment in controls) was followed by an infusion of live Escherichia
      coli bacteria. Endogenous glucose production, carbohydrate oxidation, glucose and
      lactate fluxes over the liver, gastrointestinal organs, kidney, and hindleg were
      determined. Endogenous glucose production increased during septicemia in the GH
      group. The metabolic acidosis induced by septicemia was augmented by GH, but
      attenuated by IGF-1. The alanine and lactate levels were significantly higher in
      the GH- than in the IGF-1 treated animals during septicemia. IGF-1 pretreatment
      appeared to induce favorable effects while GH pretreatment might produce
      unfavorable effects on carbohydrate metabolism in septic piglets.

PMID- 9565743
TI  - Attenuation of renal ischemia-reperfusion injury in rats by allopurinol and
      prostaglandin E1.
AB  - 50 Sprague-Dawley rats were used to study the effect of allopurinol and
      prostaglandin E1 (PGE1) on renal ischemia-reperfusion injury. They underwent left
      renal ischemia for 1 h and reperfusion. A right nephrectomy was performed, and 5
      groups were made. Group AP received allopurinol 50 mg/kg and PGE1 20
      micrograms/kg; group A, allopurinol; group P, PGE1; group C, control, and group
      S, sham group. Five animals from each group were used to study renal functions
      and 5 for renal histology. The serum creatinine values were lower in the
      treatment groups compared to the controls on days 1-3 and 7 (p < 0.05). The blood
      urea nitrogen values showed a similar trend. Maximum histological damage was seen
      in group C, followed by groups A, P and AP, in this order. We conclude that
      allopurinol and PGE1 attenuate renal ischemia-reperfusion injury in rats.

PMID- 9565742
TI  - Lipid peroxidation products and antioxidant capacity in portal venous and
      systemic arterial plasma during gradual intestinal ischemia and reperfusion in
      pigs.
AB  - Intestinal ischemia may evoke an inflammatory response and eventually multiple
      organ failure. We investigated whether intestinal ischemic injury induces
      systemic lipid peroxidation and changes in the plasma antioxidant capacity in a
      pig model. Together with cardiovascular parameters, arterial and portal venous
      blood of 7 pigs were measured for thiobarbituric acid-reactive material diene
      conjugates, fluorescent chromolipids and plasma antioxidant capacity during
      graded occlusion of superior mesenteric artery and reperfusion. Plasma levels of
      lipid peroxidation products did not change significantly during graded ischemia
      and reperfusion. Portal venous plasma antioxidant capacity increased slightly
      during reperfusion (from 96.16 +/- to 3.91 to 142.49 +/- 12.01 mumol/l, p <
      0.05). Although elevated levels of free radical reaction products have been found
      in ischemia-reperfusion, we found no evidence of systemic lipid peroxidation in
      our intestinal ischemia model.

PMID- 9565744
TI  - Laser Doppler evaluation of microcirculation behaviour during an ischaemia
      reperfusion injury.
AB  - Laser Doppler flowmetry (LDF) was tested in an experimental ischaemic model on
      rat limbs to evaluate the degree of ischaemia and to find a possible correlation
      with values obtained with this device and prognosis. Under general anaesthesia,
      40 Wistar rats were submitted to 4 h and 30 min of ischaemia of the left hind
      limb. Ten rats formed the control group (group 1). Two enzymes, native superoxide
      dismutase (SOD) and SOD modified with polyethylene glycol, were employed in 15
      rats each (groups 2 and 3). Data were collected by means of LDF both in the sole
      and muscles before ischaemia (steady state), during ischaemia and at the
      beginning of reperfusion, and only in the sole after 1 h of reperfusion. A range
      of predictive (95%) perfusion values (PU) for limb healing or necrosis was
      identified at the beginning of reperfusion. During ischaemia, PU changed from 0
      to 10, both in the sole and in the muscle. A three-factor ANOVA (site, group,
      time) did not show interaction of these factors with PU (F = 1.655; p = 0.195),
      even if every single effect was significant (p < 0.0005). A two-factor ANOVA
      (group, time) showed a significant interaction of these factors with PU (F =
      4.079; p = 0.019). The logistic regression between the reperfusion PU of each
      site and the survival of the limb was observed at the beginning and after 1 h of
      reperfusion in the sole only. Furthermore, a correlation between sole and muscle
      PU at the steady state and at the beginning of the reperfusion period was
      observed. The results showed the effectiveness of LDF, which can be considered a
      quite reliable tool to evaluate the degree of ischaemia and to have a good
      correlation with prognosis in this kind of experiments.

PMID- 9565745
TI  - Effects of prostaglandin E1 on hepatic blood flow in conscious dogs with chronic
      biliary obstruction.
AB  - To evaluate the effects of prostaglandin E1 (PGE1) on the hepatic circulation in
      cholestasis, hepatic arterial blood flow (HAP), portal venous blood flow (PVF),
      cardiac output, and heart rate during PGE1 infusions were investigated before and
      2 weeks after biliary obstruction in conscious dogs by a transit-time ultrasonic
      flowmeter. In the control period, HAF and PVF increased dose dependently with the
      infusion of PGE1 from 0.05 to 0.5 micrograms/kg/min. During the biliary
      obstruction period, a lower dose of PGE1 increased HAF and PVF. The plasma
      concentration level of PGE1 during the infusion of PGE1 was significantly higher
      at each dose in the cholestatic animals. These results suggest that the
      metabolism of PGE1 is attenuated by cholestasis. Plasma PGE1 concentrations
      should be useful in deciding the optimal dose of PGE1.

PMID- 9565746
TI  - Blood flow in rat gastrocnemius muscle and Achilles tendon after Achilles
      tenotomy.
AB  - The effect of Achilles tenotomy on resting blood flow of rat gastrocnemius muscle
      and Achilles tendon was studied by radioactive microspheres. Tenotomy produced an
      immediate, marked decrease in both intramuscular and intratendinous blood flow
      and it remained significantly lowered at both sites till the end of the
      observation period, i.e., day 18 after tenotomy. The decrease in the resting
      blood flow was more rapid and pronounced in the Achilles tendon than in the
      gastrocnemius muscle. Although the blood flow of the Achilles tendon started to
      recover after the 4th postoperative day, it was still 33% (statistically not
      significant) lower than that in the controls 18 days after tenotomy. In the
      gastrocnemius muscle, the 18-day deficit was 38% (p < 0.001), respectively. The
      results indicate that after division of a rat Achilles tendon the resting blood
      flow to the gastrocnemius muscle and Achilles tendon is not adequately restored,
      remaining at a significantly lowered level even 18 days after tenotomy.

PMID- 9565736
TI  - Adverse effects and drug interactions associated with local and regional
      anaesthesia.
AB  - Systemic and localised adverse effects of local anaesthetic drugs usually occur
      because of excessive dosage, rapid absorption or inadvertent intravascular
      injection. Small children are more prone than adults to methaemoglobinaemia, and
      the combination of sulfonamides and prilocaine, even when correctly administered,
      should be avoided in this age group. The incidence of true allergy to local
      anaesthetics is rare. All local anaesthetics can cause CNS toxicity and
      cardiovascular toxicity if their plasma concentrations are increased by
      accidental intravenous injection or an absolute overdose. Excitation of the CNS
      may be manifested by numbness of the tongue and perioral area, and restlessness,
      which may progress to seizures, respiratory failure and coma. Bupivacaine is the
      local anaesthetic most frequently associated with seizures. Treatment of CNS
      toxicity includes maintaining adequate ventilation and oxygenation, and
      controlling seizures with the administration of thiopental sodium or
      benzodiazepines. Cardiovascular toxicity generally begins after signs of CNS
      toxicity have occurred. Bupivacaine and etidocaine appear to be more cardiotoxic
      than most other commonly used local anaesthetics. Sudden onset of profound
      bradycardia and asystole during neuraxial blockade is of great concern and the
      mechanism(s) remains largely unknown. Treatment of cardiovascular toxicity
      depends on the severity of effects. Cardiac arrest caused by local anaesthetics
      should be treated with cardiopulmonary resuscitation procedures, but bupivacaine
      induced dysrhythmias may be refractory to treatment. Many recent reports of
      permanent neurological complications involved patients who had received
      continuous spinal anaesthesia through a microcatheter. Injection of local
      anaesthetic through microcatheters and possibly small-gauge spinal needles
      results in poor CSF mixing and accumulation of high concentrations of local
      anaesthetic in the areas of the lumbosacral nerve roots. In contrast to
      bupivacaine, the hyperbaric lidocaine (lignocaine) formulation carries a
      substantial risk of neurotoxicity when given intrathecally. Drugs altering plasma
      cholinesterase activity have the potential to decrease hydrolysis of ester-type
      local anaesthetics. Drugs inhibiting hepatic microsomal enzymes, such as
      cimetidine, may allow the accumulation of unexpectedly high (possibly toxic)
      blood concentrations of lidocaine. Reduction of hepatic blood flow by drugs or
      hypotension will decrease the hepatic clearance of amide local anaesthetics.
      Special caution must be exercised in patients taking digoxin, calcium antagonists
      and/or beta-blockers.

PMID- 9565747
TI  - Relationship of p53 and vascular endothelial growth factor expression of
      clinicopathological factors in human scirrhous gastric cancer.
AB  - Although scrirrhous cancer has the highest malignant potential among various
      types of gastric cancer, its pathogenesis is still unclear. The relationship
      between expression of p53 or vascular endothelial growth factor (VEGF) and
      clinicopathological variables was investigated by immunohistochemical analysis of
      archival specimens from 40 patients with scirrhous gastric cancer. Staining for
      p53 and VEGF was observed in the nuclei and cytoplasm of the tumor cells,
      respectively. There was no significant association between expression of p53 or
      VEGF and sex, age, depth of invasion, lymph node metastasis or histological
      stage. Peritoneal dissemination was the most frequent mode of recurrence, and the
      depth of tumor invasion was a crucial factor. The recurrence rate was 83.9% (2/9)
      in patients without serosal invasion. Only 7 out of 40 patients (17.5%) survived
      without recurrence. Among them, the VEGF-positive rate was 14.3% (1/7), whereas
      it was 52.6% (10/19) in the patients with recurrence. There was no correlation
      between p53 and VEGF staining. These findings suggest that the progression of
      scirrhous gastric cancer may be promoted by VEGF overexpression, which is not
      upregulated by p53 mutation.

PMID- 9565748
TI  - Effect of omental angiogenic lipid factor on revascularization of
      autotransplanted spleen in dogs.
AB  - Since the turn of the century, studies have been carried out showing that the
      omentum contains a factor which enhances revascularization of ischemic tissues.
      This study was conducted for a period of 3 months and was designed to evaluate
      the effect of an omental lipid fraction on neovascularization of autotransplanted
      spleen chips in dogs. Twelve dogs underwent splenectomy and autotransplantation
      of 5 splenic chips into an omental pouch. In 4 dogs, the splenic chips were
      immersed in omental angiogenic lipid factor (OAF), while on another 4 dogs, an
      intramuscular injection of 4 cm3 of OAF was given each day for 7 days
      postoperatively. A further 4 dogs were not given any of the above treatments
      (control group). Serial angiographies and histologic examinations demonstrated
      better neovascularization and regeneration of the transplanted spleen in the dogs
      from the immersion plus injection group. These data suggest that the omental
      lipid fraction contains a factor which induces a better regeneration of splenic
      transplants.

PMID- 9565749
TI  - Cellular signal level of cyclic AMP and functional integrity of the small bowel
      after ischemic preservation: an experimental pilot study in the rat.
AB  - The intestinal mucosa is one the tissues most sensitive to ischemia. Anoxia of
      the gut is known to result in an early impairment of cellular permeability and
      transcapillary barrier function upon reperfusion. In vitro, an increased
      permeability of endothelial cell monolayers could be shown to be related to a
      decrease in cellular content of cyclic AMP (cAMP). Thus, the present study was
      aimed at investigating the role of the cellular cAMP second messenger signal in
      the context of intestinal ischemia/reperfusion injury after cold preservation.
      Segments of the upper jejunum were isolated from Wistar rats with vascular
      pedicle and flushed with 10 ml of UW preservation solution. The intestinal lumen
      was rinsed with 10-15 ml of UW solution and the organ was stored immersed in UW
      solution at 4 degrees C for 4 or 18 h. After 18 h of cold ischemic storage
      structural and functional integrity of the preparation was tested by perfusion
      via the vascular system with modified Krebs-Henseleit buffer and the intestinal
      lumen with saline solution (containing 200 mg % of galactose) for 30 min. In half
      of the experiments, dibutyryl-cAMP a membrane permeable cAMP analogue, was
      admixed to the flush solution (2 mM). It was found that tissue levels of cAMP
      linearily decreased to 34% during 18 h of ischemic preservation in UW. Addition
      of dibutyryl cAMP significantly improved postischemic recovery of the intestinal
      preparations by decreasing cellular loss of lactic dehydrogenase (18.2 +/- 4.6
      vs. 7.6 +/- 2.6 U/I) and improving intestinal absorbtion of galactose from the
      luminal circuit (0.18 +/- 0.14 vs. 0.36 +/- 0.14 mg %) after 30 min of oxygenated
      reperfusion, but was not effective to reduce transcapillary water loss into the
      gut lumen. It is concluded that the anoxia-related decrease of the cellular cAMP
      level may represent a codeterminator influencing postischemic recovery of the
      small bowel and that the control of the cAMP signal of ischemic intestines might
      improve the quality of cold preservation of the gut prior to transplantation.

PMID- 9565750
TI  - Analysis and design of three-stranded coiled coils and three-helix bundles.
AB  - Three-stranded coiled coils and three-helix bundles are increasingly being
      identified in proteins. Design and engineering on the scaffolds of these motifs
      is a potential route towards combating associated viral infections as well as
      introducing novel functional sites.

PMID- 9565751
TI  - Folding rate dependence on the chain length of RNA-like heteropolymers.
AB  - BACKGROUND: Computer experiments and analytical estimates have shown that protein
      and RNA chains can reach their most stable folds without an exhaustive search
      over all their possible conformations. Protein-like chain folding proceeds via a
      specific nucleus and under conditions optimal for the fastest folding of these
      chains the dependence of the folding time (t) on the chain length (L) is in
      accord with the power law t integral of Lb (b is a constant). RESULTS: Using
      Monte-Carlo folding simulations for a simple model of RNA secondary structure
      formation, we estimated the RNA chain length dependence of the time necessary to
      reach the lowest energy fold. Our results are compatible with a relatively weak
      power dependence of the folding time on the chain length, t integral of Lb. Such
      dependencies have been observed for different folding conditions, both for random
      sequences (here, b > 5) and for sequences edited to stabilize their lowest energy
      folds (for extremely edited sequences b < 2). Although folding transitions in RNA
      chains are not an all-or-none type in terms of thermodynamics, they proceed via a
      folding nucleus in terms of kinetics. The peculiarity (compared with protein
      folding) is that the RNA critical nucleus is big and non-specific. CONCLUSIONS:
      We have obtained a general scaling for the dependence of the RNA secondary
      structure on the chain length. The obtained power dependence is very weak
      compared with an exponential dependence for an exhaustive sorting.

PMID- 9565752
TI  - Reading protein sequences backwards.
AB  - BACKGROUND: Reading a protein sequence backwards provides a new polypeptide that
      does not align with its parent sequence. The foldability of this new sequence is
      questionable. On one hand, structure prediction at low resolution using lattice
      simulations for such a protein provided a model close to the native parent fold
      or to a topological mirror image of it. On the other hand, there is no
      experimental evidence yet to tell whether such a retro protein folds (and to
      which structure) or not. RESULTS: In this work, we have analysed the possibility
      of a retro protein folding in two different ways. First, we modelled the retro
      sequence of the alpha-spectrin SH3 domain through distance geometry and molecular
      dynamics. This contradicted the plausibility of a mirror image of the native
      domain, whereas basic considerations opposed the likelihood of the native fold.
      Second, we obtained experimental evidence that the retro sequences of the SH3
      domain, as well as the B domain of Staphylococcal protein A and the B1 domain of
      Streptococcal protein G, are unfolded proteins, even though some propensities for
      the formation of secondary structures might remain. CONCLUSIONS: Retro proteins
      are no more similar to their parent sequences than any random sequence despite
      their common hydrophobic/hydrophilic pattern, global amino acid composition and
      possible tertiary contacts. Although simple folding models contribute to our
      global understanding of protein folding, they cannot yet be used to predict the
      structure of new proteins.

PMID- 9565753
TI  - Coupling protein stability and protein function in Escherichia coli CspA.
AB  - BACKGROUND: CspA is a small protein that binds single-stranded RNA and DNA. The
      binding site of CspA consists of a cluster of aromatic amino acids, which form an
      unusually large nonpolar patch on the surface of the protein. Because nonpolar
      residues are generally found in the interiors of proteins, this cluster may have
      evolved to bind nucleic acids at the expense of protein stability. RESULTS: Three
      neighboring phenylalanines have been mutated singly and in combination to leucine
      and to serine. All mutations adversely affect DNA binding. Surprisingly, all
      mutations, and especially those to serine, are destabilizing. CONCLUSIONS: The
      aromatic cluster in CspA is required not only for protein function but also for
      protein stability. This result is pertinent to the design of beta-sheet proteins
      and single-stranded nucleic acid binding proteins, whose binding mode is proposed
      to be of aromatic-aromatic intercalation.

PMID- 9565754
TI  - Design and NMR analyses of compact, independently folded BBA motifs.
AB  - BACKGROUND: Small folded polypeptide motifs represented highly simplified systems
      for theoretical and experimental studies on protein structure and folding. We
      have recently reported the design and characterization of a metal-ion-independent
      23-residue peptide with a beta beta alpha structure (BBA1), based on the zinc
      finger domains. To understand better the determinants of structure for this small
      peptide, we investigated the conformational role of the synthetic residue 3-(1,
      10-phenanthrol-2-yl)-L-alanine (Fen) in BBA1. RESULTS: NMR analysis revealed that
      replacing the Fen residue of peptide BBA1 by either of the natural amino acids
      tyrosine (BBA2) or tryptophan (BBA3) resulted in conformational flexibility in
      the sheet and loop regions of the structure. This conformational ambiguity was
      eliminated in peptides BBA4 and BBA5 by including charged residues on the
      exterior of the beta hairpin designed to both select against the undesired fold
      and stabilize the desired structure. The evaluation of two additional peptides
      (BBA6 and BBA7) provided further insight into the specific involvement of the
      surface polar residues in the creation of well-defined structure in BBA4 and
      BBA5. The sequences of BBA5, BBA6 and BBA7 include only one non-standard amino
      acid (D-proline), which constrains a critical engineered type II' turn.
      CONCLUSIONS: Manipulation of residues on the exterior of small beta beta alpha
      motifs has led to the design of 23-residue polypeptides that adopt a defined
      tertiary structure in the absence of synthetic amino acids, increasing the
      availability and expanding the potential uses of the BBA motif. The importance of
      negative design concepts to the creation of structured polypeptides is also
      highlighted.

PMID- 9565755
TI  - Protein hydration and unfolding--insights from experimental partial specific
      volumes and unfolded protein models.
AB  - BACKGROUND: The partial specific volume of a protein is an experimental quantity
      containing information about solute-solvent interactions and protein hydration.
      We use a hydration-shell model to partition the partial specific volume into an
      intrinsic volume occupied by the protein and a change in the volume occupied by
      the solvent resulting from the solvent interactions with the protein. We seek to
      extract microscopic information about protein hydration and unfolding from
      experimental volume measurements without using computer simulations. We employ
      the idea that the protein-solvent interaction will be proportional to the surface
      area of the protein. RESULTS: A linear relationship is obtained when the
      difference between the experimental protein partial specific volume and its
      intrinsic volume is plotted as a function of the protein solvent-accessible
      surface area. The effect of using different protein volume definitions on the
      analysis of protein volumetric properties is discussed. Volumetric data are used
      to test a model for the unfolded state of proteins and to make predictions about
      the denatured state. CONCLUSIONS: The linear relationship between hydration-shell
      volume change and accessible surface area reflects the similar surface properties
      (fractional composition of nonpolar, polar and charged surface) among a diverse
      set of proteins. This linear relationship is found to be independent of how the
      solution is partitioned into solute and solvent components. The interpretation of
      hydration shell versus bulk water properties is found to be very model dependent,
      however. The maximally exposed unfolded protein model is found to be inconsistent
      with experimental volume changes of unfolding.

PMID- 9565756
TI  - Tolerance of a protein helix to multiple alanine and valine substitutions.
AB  - BACKGROUND: Protein stability is influenced by the intrinsic secondary structure
      propensities of the amino acids and by tertiary interactions, but which of these
      factors dominates is not known in most cases. We have used combinatorial
      mutagenesis to examine the effects of substituting a good helix-forming residue
      (alanine) and a poor helix-forming residue (valine) at many positions in an alpha
      helix of a native protein. This has allowed us to average over many molecular
      environments and assess to what extent the results reflect intrinsic helical
      propensities or are masked by tertiary effects. RESULTS: Alanine or valine
      residues were combinatorially substituted at 12 positions in alpha-helix lambda
      repressor. Functional proteins were selected and sequenced to determine the
      degree to which each residue type was tolerated. On average, valine substitutions
      were accommodated slightly less well than alanine substitutions. On a positional
      basis, however, valine was tolerated as well as alanine at the majority of sites.
      In fact, alanine was preferred over valine statistically significantly only at
      four sites. Studies of mutant protein and peptide stabilities suggest that
      tertiary interactions mask the intrinsic secondary structure propensity
      differences at most of the remaining residue positions in this alpha helix.
      CONCLUSIONS: At the majority of positions in alpha-helix lambda repressor,
      tertiary interactions with other parts of the protein can be viewed as an
      environmental "buffer" that help to diminish the helix destabilizing effects of
      valine mutations and allow these mutations to be tolerated at frequencies similar
      to alanine mutations.

PMID- 9565757
TI  - Cooperativity in protein folding: from lattice models with sidechains to real
      proteins.
AB  - BACKGROUND: Over the past few years novel folding mechanisms of globular proteins
      have been proposed using minimal lattice and off-lattice models. The factors
      determining the cooperativity of folding in these models and especially their
      explicit relation to experiments have not been fully established, however.
      RESULTS: We consider equilibrium folding transitions in lattice models with and
      without sidechains. A dimensionless measure, omega c, is introduced to
      quantitatively assess the degree of cooperativity in lattice models and in real
      proteins. We show that larger values of omega c resembling the values seen in
      proteins are obtained in lattice models with sidechains. The enhanced
      cooperativity of such models results from possible denser packing of sidechains
      in the interior of the model polypeptide chain. We also establish that omega c
      correlates extremely well with sigma T = (T o - T f) /T o, where T o and T f are
      collapse and folding transition temperatures, respectively. These theoretical
      ideas are used to analyze folding transitions in two-state folders (RNase A,
      chymotrypsin inhibitor 2, fibronectin type III modules and tendamistat) and three
      state folders (apomyoglobin and lysozyme). The values of omega c extracted from
      experiments show a correlation with sigma T (suitably generalized when folding is
      induced by denaturants or acid). CONCLUSIONS: A quantitative description of the
      cooperative transition of real proteins can be made by lattice models with
      sidechains. The degree of cooperativity in minimal models and real proteins can
      be expressed in terms of the single parameter sigma, which can be estimated from
      experimental data.

PMID- 9565758
TI  - What is the probability of a chance prediction of a protein structure with an
      rmsd of 6 A?
AB  - BACKGROUND: The root mean square deviation (rmsd) between corresponding atoms of
      two protein chains is a commonly used measure of similarity between two protein
      structures. The smaller the rmsd is between two structures, the more similar are
      these two structures. In protein structure prediction, one needs the rmsd between
      predicted and experimental structures for which a prediction can be considered to
      be successful. Success is obvious only when the rmsd is as small as that for
      closely homologous proteins (< 3 A). To estimate the quality of the prediction in
      the more general case, one has to compare the native structure not only with the
      predicted one but also with randomly chosen protein-like folds. One can ask: how
      many such structures must be considered to find a structure with a given rmsd
      from the native structure? RESULTS: We calculated the rmsd values between native
      structures of 142 proteins and all compact structures obtained in the threading
      of these protein chains over 364 non-homologous structures. The rmsd
      distributions have a Gaussian form, with the average rmsd approximately
      proportional to the radius of gyration. CONCLUSIONS: We estimated the number of
      protein-like structures required to obtain a structure within an rmsd of 6 A to
      be 10(4)-10(5) for chains of 60-80 residues and 10(11)-10(12) structures for
      chains of 160-200 residues. The probability of obtaining a 6 A rmsd by chance is
      so remote that when such structures are obtained from a prediction algorithm, it
      should be considered quite successful.

PMID- 9565759
TI  - [The current status of psychotherapy research in schizophrenia].
AB  - After a preponderance of psychoanalytically orientated individual psychotherapy,
      family therapy dominated in recent years, in most cases of limited duration.
      Family therapy proved very helpful in unburdening relatives and deemotionalising
      familiar surroundings. Earlier studies demonstrated the significance of family
      therapy for relapse prevention, but controlled studies could not show that these
      methods were more effective than careful neuroleptic medication. Time-limited
      group psychotherapy was also criticised for lack of controlled studies. Though
      these modalities were shown to be effective in individual cases, long-lasting and
      relapse-preventing effects could not be shown. Psychological therapies lasting
      for only some months obviously overcharge patients in some cases and may
      occasionally even have counterproductive effects.

PMID- 9565760
TI  - [Hearing loss as the leading symptom in anterior inferior cerebellar artery
      infarction].
AB  - Hearing impairment is a rare but characteristic symptom of vertebrobasilar
      occlusive disease. Two patients with anterior inferior cerebellar artery (AICA)
      infarction and hearing loss as presenting complaint, are described. In patient 1
      progressive bilateral AICA infarction was caused by occlusion of the basilar
      artery, verified by transcranial Doppler sonography. Initial dizziness and
      bilateral hearing loss were followed by ataxia, dysarthria, dysphagia and right
      facial sensory impairment. Hearing loss improved during the second week, parallel
      to a temporary partial recanalisation of the basilar artery, but the patient
      subsequently developed further progressive brain stem symptoms and died. A right
      sided AICA-infarction was diagnosed in patient 2. Initial symptoms were right
      sided deafness and dizziness. Neurological examination revealed nystagmus, ataxia
      and involvement of th 5th and 6th cranial nerve. A progressive improvement of
      hearing loss and total recovery of the other brain stem symptoms was evident. In
      conclusion every patient with sudden hearing loss should be examined for
      additional brain stem symptoms since this can be the presenting sign of a life
      threatening basilar artery thrombosis.

PMID- 9565761
TI  - [Oxidative stress in the pathogenesis of Alzheimer's disease and antioxidant
      neuroprotection].
AB  - Alzheimer's disease (AD) is one of the most frequent causes of dementia in the
      aged. The elucidation of the pathomechanisms of this neurodegenerative disease
      with age, as the only risk factor for the majority of cases, is in the centre of
      the efforts of molecular and cellular neurobiology in preclinical research.
      Various findings point to the involvement of the amyloid beta protein (A beta) in
      the pathogenesis and progression of AD. Precipitated A beta aggregates are found
      in the brain of AD patients post mortem in the so-called plaques, a major
      histopathological hallmark of this progressive destructive disease. A beta can be
      toxic to cultivated neuronal cells only in its aggregated fibril form. After
      interaction with the neuronal cell membrane, these aggregates can induce
      intracellular oxidative events and can lead to the release of so-called free
      radicals. This is just one important finding for the involvement of oxidative
      events in the nerve cell degeneration in AD supporting the oxidative stress
      hypothesis. Furthermore, different neurochemical methods revealed many additional
      traits and scars of oxidative reactions in the brain of AD patients. Inflammatory
      events also seem to take part in the generation of an oxidative environment and
      therefore in nerve cell death as well. In addition, various age-dependent
      pathophysiological changes can increase neuronal vulnerability. Different
      antioxidants can protect cultivated neurons against A beta toxicity, but also
      against other oxidative stressors relevant to the disease. Besides the classical
      lipophilic antioxidant vitamin E, the female sex hormone oestrogen could also
      play an important neuroprotective role as an antioxidant, as was shown recently.
      Oestrogen, oestrogen derivatives, but also other potential free radical
      scavengers could block the accumulation of oxidative events on the long run and
      could, therefore, possibly slow down or prevent progressive nerve cell death of
      AD, which occurs over decades. If future clinical trials using antioxidants as
      neuroprotectants in AD would also support the oxidative stress hypothesis of the
      aetiopathogenesis of AD, antioxidants identified in the laboratory could then
      find their way more and more into the clinical treatment of Alzheimer's dementia.

PMID- 9565762
TI  - [History of scientific research films in neurology in germany 1895-1929].
AB  - Based on a systematic journal survey, an account is given of the history of
      research films in neurology and psychiatry in Germany in the era of the silent
      film 1895-1929. In 1897, Paul Schuster of Berlin was the first who filmed
      patients with a variety of movement disorders. Since 1927, Otto Lowenstein of
      Bonn developed the method of pupillography which was based on single-frame
      analysis and allowed quantitative evaluation of pupillary responses. Film
      recordings of epileptic fits proved to be of value in the scientific study of
      epilepsy. The few films copies that have survived the passage of time are
      valuable documents of medical history.

PMID- 9565763
TI  - [The revised definitions of schizophrenic disorders in ICD-10 and DSM-IV].
AB  - Starting from the original concept of "dementia praecox", in this article, the
      ICD 10 and DSM-IV revisions of their respective definitions of schizophrenia are
      made more transparent and evaluative in regards to their development. For the ICD
      10 definition, the schizophrenia concept of K. Schneider and its characteristic
      orientation towards diagnostic validity had a pre-eminent impact, whereas in DSM
      IV the authors intended to follow the schizophrenia concept of E. Bleuler and
      thereby aimed at placing greater emphasis on the negative symptomatology.
      However, the results of the revision of schizophrenic disorders of this
      diagnostic system surprisingly leaned again towards the concept of K. Schneider.
      With regard to own findings on the diagnostic validity of positive and negative
      symptoms, it is shown that this result is justified in accordance with the
      present state of the art in schizophrenia research. In addition, the article
      deals with the definitions of schizotype features, prodromal and residual
      symptoms in these new diagnostic systems and critically evaluates these elements.
      To sum up it is clear that the recent definitions are based on the German
      psychopathological tradition on the one hand and the empirical findings of the
      last centuries on the other. Taking the latter into account, this might lead to a
      new understanding of schizophrenic disorders in the future.

PMID- 9565765
TI  - Drugs interacting with G protein alpha subunits: selectivity and perspectives.
AB  - Extracellular signal molecules as diverse as hormones, neurotransmitters and
      photons use a signal transduction pathway involving a receptor, a G protein and
      effectors. Compounds that interact directly with G proteins can mimic the
      receptor-G protein interaction or can block the activation of G proteins by
      receptors. Several binding sites exist on the G alpha protein that may be
      exploited for the design of synthetic stimulatory or inhibitory ligands. The
      effector binding site is regulated by endogenous proteins and appears to be a
      target for selective exogenous ligands. The GTP binding site presents a large
      homology within the G protein families and therefore the nucleotide analogs might
      not be considered as a tool to discriminate between the G protein subclasses. In
      contrast, different experimental strategies have substantiated the specificity in
      the interaction between a receptor and a G protein, the receptor binding site of
      G proteins should be considered as potential drug targets. Drugs interfering with
      this site such as mastoparan and related peptides, GPAnt-2 and suramin, are lead
      compounds in the design of selective G protein antagonists. Benzalkonium chloride
      and methoctramine have agonist or antagonist properties, depending on G protein
      subtypes. Such compounds would be very useful to delineate the functions of G
      proteins and G protein-coupled receptors, to understand some side effects of
      drugs used in therapy and to develop new therapeutic agents.

PMID- 9565766
TI  - Receptors involved in the positive inotropic action induced by dopamine on the
      ventricle of a 7-day-old chick embryo heart.
AB  - Earlier experiments only revealed involvement of sympathetic pre-synaptic
      dopaminergic receptors in dopamine induced inotropism in myocardium. We therefore
      used electrically stimulated (1 Hz) isolated 7-day-old chick embryo heart
      ventricles, thought to be devoid of functional sympathetic nerves, to re
      investigate post-synaptic receptors involvement and particularly that of
      dopaminergic receptors in the positive inotropic effect of dopamine. The results
      showed that noradrenaline, isoprenaline and dopamine produced a positive
      inotropic effect with a similar efficacy and with an order of potency as follows:
      Isoprenaline = Noradrenaline > Dopamine. Tyramine induced no significant
      modification of the "initial tension" indicating that functional sympathetic
      innervation and/or releasable endogenous catecholamines were not demonstrable in
      the 7-day-old chick embryo heart ventricle. Propranolol (1 microM) competitively
      antagonized the positive inotropic response to isoprenaline, noradrenaline and
      dopamine, meanwhile phentolamine (3 microM) failed to significantly modify the
      effects of both noradrenaline and dopamine, indicating that these catecholamines
      induced their positive inotropic effects via stimulation of beta-adrenoceptors;
      involvement of alpha-adrenergic receptors stimulation was not demonstrable in
      these effects. Moreover, haloperidol (2 microM) antagonized the positive
      inotropic response to dopamine but had not any significant effect on the response
      to isoprenaline. The combined application of both propranolol and haloperidol
      antagonized the positive inotropic response to dopamine to a greater extent than
      when these two antagonists were given alone. Consequently, post-synaptic
      dopaminergic receptors were also involved in the positive inotropic effect of
      dopamine. Furthermore, in preparations in which sodium channels were inactivated
      by high potassium physiological salt solution, high concentrations of dopamine
      (0.1 mM to 1 mM) induced a slow developing electrical and positive inotropic
      responses which were also inhibited by propranolol and haloperidol, but not by
      phentolamine. These latter results indicated that like beta-adrenergic
      stimulation, the slow inward calcium current activated by stimulation of
      adenylate cyclase, was at least in part involved in the positive inotropic
      response to dopamine. In conclusion, dopamine induced its positive inotropism via
      stimulation of post-synaptic beta-adrenergic and dopaminergic receptors. The
      contribution of dopaminergic receptors in this positive inotropic effect might be
      of the DA-2 receptors since haloperidol used had been reported to be more DA-2
      than DA-1 antagonist. These DA-2 receptors subtypes would mediate activation of
      adenylate cyclase.

PMID- 9565767
TI  - Potentiating effect of nicorandil on the adenosine A2 receptor-mediated
      vasodepression in rats: potential role for KATP channels.
AB  - The effects of nicorandil on systemic blood pressure (SBP) and heart rate (HR)
      responses to adenosine were compared with those to N6-cyclopentyladenosine (CPA),
      a selective adenosine A1 receptor agonist, and 5'-(N-cyclopropyl)
      carboxamidoadenosine (CPCA), a selective adenosine A2 receptor agonist, in
      anesthetized rats. When injected intravenously (i.v.), single bolus doses of CPCA
      (0.01-1.0 micrograms/kg), like adenosine (30 micrograms/kg), elicited dose
      dependent decreases in SBP scarcely affecting HR, while CPA (0.03-1.0
      micrograms/kg) produced only reduction of HR without influencing SBP. The
      enhancement of the vasodepressor response to CPCA, like adenosine, was induced by
      the i.v. infusion of either nicorandil (10 micrograms/kg per min) or cromakalim
      (0.1 micrograms/kg per min), but the response to CPA in HR remained unmodified
      during the infusion of nicorandil as well as cromakalim. After i.v. treatment
      with glibenclamide (20 mg/kg), and adenosine triphosphate (ATP)-sensitive K+
      channel blocker, or 3,7-dimethyl-1-propargylxanthine (DMPX) (1 mg/kg), a
      selective antagonist of adenosine A2 receptor, not only CPCA action but also the
      enhancement of CPCA action by nicorandil and cromakalim were significantly
      attenuated. Similar results were obtained in the case of single bolus i.v.
      adenosine. The present result indicates that the augmentation of the adenosine
      action by nicorandil appears to be mediated by activation of ATP-sensitive K+
      channels, closely linked with stimulation on A2 receptors by adenosine.

PMID- 9565768
TI  - Contractile responses evoked by dihydroergotamine, naratriptan and sumatriptan in
      the canine isolated coronary artery.
AB  - Contractile responses evoked by the 5-HT IB/D receptor agonists,
      dihydroergotamine, naratriptan and sumatriptan, were compared in canine isolated
      coronary artery rings before and after endothelial dysfunction as obtained by
      inhibition of nitric oxide synthase with Nw-nitro-L-arginine methyl ester (L
      NAME; 10 microM). The three agonists contracted rings in the potency order of
      dihydroergotamine (geometric mean pD2 value with 95% confidence limits in
      parentheses: 6.9 [5.3-7.9] and 7.0 [5.4-7.3] in the absence and presence of
      nitric oxide synthase (NOS) inhibition [I], respectively) > or = naratriptan (6.8
      [5.7-7.3] and 6.4 [5.7-6.6]) > sumatriptan (4.8 [3.6-5.6] and 5.0 [3.6-5.6])
      independently of the presence or absence of L-NAME. In absence of L-NAME,
      efficacy, as assessed by the mean maximal contractile response (Emax), tended to
      be greater, although not significantly, for sumatriptan and naratriptan compared
      to dihydroergotamine. L-NAME per se markedly increased developed tension (43.0 +/
      4.6 mN; n = 50) and potentiated maximal responses (0.6 +/- 0.2 and 10.7 +/- 2.4
      mN for dihydroergotamine in the absence and presence of L-NAME respectively; 1.7
      +/- 0.6 and 18.7 +/- 3.7 mN for naratriptan; 2.5 +/- 0.6 and 21.3 +/- 3.8 mN for
      sumatriptan; P < 0.01 in each case). Emax values of sumatriptan and naratriptan
      were greater than those produced by dihydroergotamine in the presence of L-NAME
      but remained lower than the sub-maximal contractile responses evoked by the
      thromboxane A2 analogue, U-46619 (ie, 32.4 +/- 5.2 mN in the absence of L-NAME; n
      = 50), or L-NAME per se. In conclusion, 5-HT IB/D receptor agonist efficacies in
      contracting coronary arteries are relatively low under basal conditions and are
      potentiated in the presence of a dysfunctional endothelium, whereas agonist
      potencies remain unaffected.

PMID- 9565769
TI  - Cardioprotective profile of MET-88, an inhibitor of carnitine synthesis, and
      insulin during hypoxia in isolated perfused rat hearts.
AB  - 3-(2,2,2-trimethylhydrazinium) propionate (MET-88) is an inhibitor of carnitine
      synthesis. This study was carried out to investigate whether or not reduction of
      carnitine content could attenuate hypoxic damage in isolated perfused rat hearts.
      Rats were divided into four groups: 1) vehicle control; 2) pretreatment with MET
      88 (MET-88); 3) application of insulin (500 muU/mL) in the perfusate (insulin);
      and 4) pretreatment with MET-88 and application of insulin (MET-88 + insulin).
      MET-88 (100 mg/kg) was orally administered once a day for 10 days until the day
      before the experiments. Hearts were initially perfused for a 10 min period under
      normoxia, followed by a 30 min period under hypoxia. Hearts were frozen at the
      end of hypoxia for the measurement of high-energy phosphates, carnitine
      derivatives, and glycolysis intermediates. In a separate series of untreated and
      MET-88 treated hearts, exogenous glucose and palmitate oxidation was measured.
      MET-88 decreased the extent of the depression of cardiac contractility (+dP/dt),
      and aortic flow during the hypoxic state. Insulin also improved cardiac function,
      and co-treatment of MET-88 and insulin additionally improved cardiac function
      during hypoxia. MET-88 prevented the decrease of high-energy phosphate and the
      increase of long-chain acylcarnitine after 30 min of hypoxic perfusion. In
      addition, MET-88 increased the steady state of glucose oxidation in hypoxic
      perfused rat hearts. These results indicate that MET-88 has cardioprotective
      effects on contractile function and energy metabolism of isolated perfused rat
      hearts in a hypoxic condition. Preventing the accumulation of long-chain
      acylcarnitine may serve to protect hypoxic hearts.

PMID- 9565770
TI  - Vitamin E analogues reduce the incidence of ventricular fibrillations and
      scavenge free radicals.
AB  - The aim of our study was to analyse the protective effects of different alpha
      tocopherol analogues 1) against fibrillations induced by an ischemia-reperfusion
      sequence, and 2) to further investigate in vitro the radical scavenging
      properties of these analogues by two sensitive methods. Concerning 1: isolated
      rat hearts underwent 10 min of coronary ligation followed by reperfusion and the
      alpha-tocopherol analogues were infused 15 min before occlusion. Functional
      parameters including heart rate and fibrillations were recorded. Concerning 2:
      the beta-phycoerythrin assay was utilised to determine the oxygen radical
      absorbing capacity (ORAC) of these vitamin E analogues against peroxyl radicals.
      Electron paramagnetic resonance (EPR) was used to measure their scavenger
      abilities on hydroxyl radical and superoxide anion production. Concerning 1:
      ventricular fibrillation times were reduced for all analogues treated hearts at
      concentrations of 1 microM and 5 microM, with Trolox being the most efficacious.
      Concerning 2: in our experimental conditions of intense production of free
      radicals, scavenging IC50 values for hydroxyl radical were 1.15, 2.17 and 4.04 mM
      for Trolox, MDL 74270 and MDL 74366 respectively. Superoxide anion IC50 values
      were 1.0 and 6.75 mM for Trolox and MDL 74270. Our results show that water
      soluble analogues of vitamin E are effective in the prevention of coronary
      ligation induced reperfusion arrhythmia, under our experimental conditions.
      Moreover, our data demonstrate that these vitamin E analogues are effective
      scavengers for a variety of radicals. Our studies support the view that compounds
      that can either inhibit the formation or scavenge free radicals can protect the
      heart against arrhythmia associated with ischemia-reperfusion.

PMID- 9565771
TI  - Effects of alpha 1-acid glycoprotein in different rodent models of shock.
AB  - It was the aim of the present study to investigate the effects of the acute phase
      protein alpha 1-acid glycoprotein in different models of shock. The human plasma
      preparation used was without effect on mortality in lipopolysaccharide-injected
      mice when administered in two different doses (1 or 0.33 g/kg i.v.) and according
      to different treatment schedules. The same preparation significantly increased
      survival rate (48 h) in rats with septic peritonitis. This effect was seen when
      alpha 1-acid glycoprotein (200 mg/kg i.v.) was given 15 min prior to and 24 h
      after cecal puncture. All other dose regimes tested were without significant
      effect on survival rate. A hemorrhagic/hypovolemic shock model (including a
      defined trauma) in rats resuscitated with 200 mg/kg alpha 1-acid glycoprotein
      resulted in significantly higher values of mean arterial blood pressure, cardiac
      output and stroke volume when compared to corresponding values obtained after
      resuscitation with Ringer's solution or 200 mg/kg albumin i.v. (free of alpha 1
      acid glycoprotein; placebo formulation). Taking all other possible mechanisms of
      alpha 1-acid glycoprotein into consideration, the partially protective effects of
      the preparation are explained by enhancing the capillary barrier function and
      thereby maintaining perfusion of vital organs.

PMID- 9565772
TI  - Calcium antagonist properties of the bisbenzylisoquinoline alkaloid cycleanine.
AB  - The alkaloid cycleanine ([12aR-(12aR,24aR)]-2,3,12a,13,14,15,24,24a-octa hydro
      5,6,17,18- tetramethoxy-1,13-dimethyl-8, 11:20,23-dietheno-1H,12H
      [1,10]dioxacyclooctadecino[2,3,4-ij:11,12,13-i'j']diisoquinolin e) was extracted
      from the bulbs of Stephania glabra (Roxb) Miers and its effects on cardiac and
      smooth muscle preparations were studied and compared to those of nifedipine (1,4
      dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid
      dimethylesther). Cycleanine inhibited the KCl-induced contraction of rabbit
      aortic rings with higher potency than nifedipine. IC50s for cycleanine and
      nifedipine were 0.8 and 7.10(-9) M respectively. Cycleanine had minor effects on
      the norepinephrine-induced contraction of rabbit aortic rings. Cycleanine and
      nifedipine also depressed the contraction of rat ventricular preparations but
      with lower potency (IC50 = 3 and 0.03.10(-6) M respectively). Action potential
      duration of rat right ventricular strips was decreased by both compounds. L-type
      Ca-current (ICaL) of single rat ventricular cardiomyocytes was inhibited by
      cycleanine in a voltage- and frequency-dependent manner. With a higher potency
      nifedipine inhibited ICaL in a tonic and almost frequency-independent manner. The
      results suggest that cycleanine can act as a potent vascular selective Ca
      antagonist.

PMID- 9565773
TI  - Effect of WIN 64338, a B2 bradykinin receptor antagonist on guinea-pig tracheal
      smooth muscle cells in culture.
AB  - This study investigated the effect of the non-peptidic B2 bradykinin (BK)
      receptor antagonist WIN 64338 on BK binding and BK-induced inositol phosphate
      formation on guinea-pig tracheal smooth muscle cells in culture. The presence of
      specific and saturable binding sites for BK was demonstrated using [3H]BK.
      Scatchard analysis indicates a single population of binding sites for [3H]BK with
      a maximal density (Bmax) of 245.4 +/- 71 fmol/mg of protein and an equilibrium
      dissociation constant (Kd) of 87.7 +/- 0.12 pM. The order of potency of] B2 BK
      receptor ligands was Hoe 140 = NPC 17731 > BK > WIN 64338 > D- Arg0[Hyp3, D-Phe7]
      BK > > des-Arg9-BK, while B1 BK receptor antagonist, des-Arg9-[Leu8]-BK, was
      without effect on [3H]BK binding. These results demonstrate the presence of B2 Bk
      receptors on cultured tracheal smooth muscle cells. The cells were stimulated by
      BK, and inositol phosphate formation was determined by anion exchange
      chromatography. The stimulating effect of BK on inositol phosphate formation was
      concentration dependent (1 nM to 10 microM). The B1 BK agonist des-Arg9-BK did
      not induce inositol phosphate formation. The order of potency of B2 antagonists
      to inhibit BK-induced inositol phosphate formation was Hoe 140 = NPC 17731 > WIN
      64338 > D-Arg0[Hyp3, D-Phe7]-BK. This study demonstrates that WIN 64338 is able
      to displace [3H]BK binding and to inhibit B2-BK-induced inositol phosphate
      formation on cultured guinea-pig tracheal smooth muscle cells.

PMID- 9565774
TI  - In vitro interactions between fluoxetine or fluvoxamine and methadone or
      buprenorphine.
AB  - Methadone and buprenorphine, widely used in the treatment of opioid abuse, are
      metabolized by cytochrome P450 3A4, while fluoxetine and fluvoxamine, both
      selective serotonin reuptake inhibitors, are known to be P450 2D6 and 3A4
      inhibitors in vitro. This study deals with the in vitro interactions between
      methadone or buprenorphine and fluoxetine or fluvoxamine. Fluoxetine inhibited
      methadone N-demethylation (Ki = 55 microM), but conversely did not inhibit
      buprenorphine dealkylation. Norfluoxetine inhibited the metabolism of both
      methadone and buprenorphine metabolisms (Ki 13 and 100 microM, respectively).
      Fluvoxamine inhibited methadone N-demethylation with a Ki of 7 microM and
      buprenorphine dealkylation, uncompetitively, with a Ki of 260 microM. Finally,
      these results suggest that care should be taken when selective serotonin reuptake
      inhibitors are administered in the treatment of drug craving. This is
      particularly true in the case of fluvoxamine which is more potent than fluoxetine
      in inhibiting methadone and buprenorphine metabolism.

PMID- 9565775
TI  - Evidence for a role for bulbospinal pathways in the spinal antinociceptive effect
      of systemically administered vapreotide in normal rats.
AB  - Numerous neurotransmitters are involved in nociceptive transmission or
      regulation. Several reports have shown the analgesic effects of somatostatin and
      its analogues. Somatostatin, when given intrathecally, markedly reduced pain in
      cancer patients. Somatostatin analogues that possess a longer half-life time are
      more convenient for therapeutic use. Vapreotide, a somatostatin analogue, was
      shown to induce a long-lasting antinociceptive effect in rats. We studied the
      site and the mechanism of action of vapreotide in rats using the paw pressure
      test. Intrathecal administration of vapreotide induced no antinociception.
      Systemically administered vapreotide-induced antinociception was inhibited by
      several intrathecal (i.t.) administered antagonists (yohimbine, naloxone and to a
      lesser degree tropisetron). These results show a lack of spinal effect and
      suggest a supraspinal site of action with an involvement of noradrenergic and to
      a lesser degree serotonergic bulbospinal pathways. In addition, spinal opioid
      receptors also seen to be involved.

PMID- 9565776
TI  - In vitro antioxidant properties of calcium dobesilate.
AB  - Calcium dobesilate, a vascular protective agent, was tested in vitro for its
      scavenging action against oxygen free radicals. Calcium dobesilate was as potent
      as rutin to scavenge hydroxyl radicals (IC50 = 1.1 vs 0.7 microM, respectively).
      It was also able to scavenge superoxide radicals, but with 23 times less potency
      than rutin (IC50 = 682 vs 30 microM, respectively). Calcium dobesilate
      significantly reduced platelet activating factor (PAF)-induced chemiluminescence
      in human PMN cells and lipid peroxidation by oxygen free radicals in human
      erythrocyte membranes, although these actions required calcium dobesilate
      concentrations > or = 50 microM. Finally, in cultured bovine aortic endothelial
      cells, magnesium dobesilate reduced the increase in cytosolic free calcium
      induced by hydrogen peroxide and inhibited phenazine methosulfate-induced cell
      potassium loss. In conclusion, calcium dobesilate was effective in scavenging
      hydroxyl radicals in vitro, at therapeutically relevant concentrations.
      Conversely, higher concentrations of the compound were required to scavenge
      superoxide radicals or to protect the cells against the deleterious effects of
      intracellular reactive oxygen species. Further studies in vivo are required to
      determine if these antioxidant properties of calcium dobesilate can play a role
      in its vascular protective mechanisms.

PMID- 9565777
TI  - Alteration of lipid composition of hepatic membranes associated with manganese
      bilirubin induced cholestasis.
AB  - One hypothesis concerning the pathogenesis of manganese-bilirubin (Mn-BR)-induced
      cholestasis is that the molecular organization of the bile canalicular membrane
      is altered. The purpose of the present study was to evaluate lipid composition
      and fluidity of hepatic membranes during cholestasis in male Sprague-Dawley rats.
      To induce cholestasis, manganese (Mn, 4.5 mg/kg, intravenously [i.v.]) was given
      15 min before bilirubin (BR, 25 mg/kg, i.v.). The rats were killed 30 min after
      BR injection, at which time bile flow was decreased by approximately 40% compared
      to control values. Liver cell plasma membranes enriched in canalicular fractions
      (BCM) and plasma membranes enriched in sinusoidal and lateral fractions (PM),
      microsomes, mitochondria and cytosol were isolated by differential
      centrifugation. Total lipids were extracted and measured colorimetrically. To
      assess fluidity, membranes were incubated in vitro with fluorescent probes [1,6
      diphenyl-1,3,5-hexatriene and 1-(4'-trimethyl-ammonium-phenyl)-6-phenyl-1,3,5
      hexatriene]. After Mn-BR treatment, BCM cholesterol incorporation increased
      markedly (about 3-fold) accompanied by a decrease in fluidity. BCM phospholipid
      content was unaltered by the cholestatic challenge. In PM-enriched fractions, the
      changes in cholesterol and phospholipid content after Mn-BR treatment were not
      statistically significant (P > 0.05) compared to controls. Furthermore, the
      biochemical alterations in PM were not accompanied by changes in membrane
      fluidity. These results support the hypothesis that altered lipid composition and
      fluidity of BCM are involved in the pathogenesis of Mn-BR cholestasis.

PMID- 9565779
TI  - Identification of human and rabbit cytochromes P450 1A2 as major isoforms
      involved in thiabendazole 5-hydroxylation.
AB  - This report characterized one of the major cytochrome P450 isozyme involved in
      thiabendazole metabolism. This study was undertaken by using both cultured rabbit
      hepatocytes treated or not with drugs known to specifically induced various
      cytochromes P450 isoenzymes (i.e., P450 1A1/2 by beta-naphthoflavone, P450 2B4 by
      phenobarbital, P450 3A6 by rifampicine and P450 4A by clofibrate) and human liver
      (THLE-5) and bronchial (BEAS-2B) epithelial cells expressing or not the major
      constitutive human cytochromes P450 (i.e., CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1 or
      3A4). Only hepatocytes exposed to beta-naphthoflavone and clofibrate
      significantly metabolized thiabendazole to 5-hydroxythiabendazole. Extensive
      biotransformation of this anthelmintic only occurred in human cells expressing
      CYP1A2. Moreover, experiments performed on rabbit preparations showed good
      correlations between thiabendazole 5-hydroxylase activity and both
      ethoxyresorufin and methoxyresorufin O-dealkylase activities. Thus, CYP1A2 is a
      major isoenzyme involved in thiabendazole 5-hydroxylation.

PMID- 9565778
TI  - Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in
      cimetidine treated rats.
AB  - The aim of this work was to evaluate the effects of exogenous glutathione (GSH)
      and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX)
      from lidocaine in rats with and without the administration of cimetidine. GSH and
      NAC were administered intraperitoneally (i.p.) (1 mmol/kg) 1 hour before
      treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were
      injected i.p. with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the
      lidocaine injection. MEGX and lidocaine serum concentrations were determined by
      means of fluorescence polarization immuno-assay using the TDX system. Cimetidine
      produced a decrease in MEGX levels (from 210 +/- 18 to 164 +/- 13 ng/mL) and a
      parallel increase in lidocaine levels (from 73 +/- 22 to 172 +/- 47 ng/mL),
      consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produce a
      significant decrease in MEGX levels (151 +/- 16 and 139 +/- 14 ng/mL,
      respectively), but no significant increase in lidocaine levels were found. As
      compared to the cimetidine group, pre-treatment using either GSH or NAC with
      cimetidine produced a marked decrease in lidocaine levels (37 +/- 27 and 63 +/-
      28 ng/mL, respectively) and no modification of MEGX levels (155 +/- 12 and 165 +/
      22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate
      the lidocaine metabolism while counteracting the inhibitory effect of cimetidine.

PMID- 9565780
TI  - Plasma iron status and lipid peroxidation following thrombolytic therapy for
      acute myocardial infarction.
AB  - Free radical species have been implicated as important agents involved in
      myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing
      iron from ferritin and the released iron can cause hydroxyl formation from H2O2.
      The aim of this study was to evaluate the time-dependent increase in lipid
      peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS)
      and the relationship between lipid-peroxidation and the iron status. Peripheral
      venous blood samples were obtained from 17 men with acute myocardial infarction
      (AMI) before thrombolytic treatment (T0) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48
      hours after commencing fibrinolytic treatment. The concentration of TBARS, the
      parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine
      kinase-MB were measured. Early reperfusion was judged by regression of sinus
      tachycardia (ST) elevation and reduction of chest pain. Recanalization of
      coronary artery was evaluated by a late coronary angiography 24-96 hours after
      thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 +/
      0.80 (T0) to 4.57 +/- 1.24 (peak), and decreased to 2.96 +/- 0.40 nmol/mL plasma
      at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean
      time of the peak was observed at 9.7 +/- 7.5 hours. The iron increased
      significantly from 0.67 +/- 0.34 (T0) to 1.15 +/- 0.52 mg/L (peak), and returned
      to the pre-reperfusion to levels: 0.53 +/- 0.28 UI/L at T48 (TO vs peak: P <
      0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was
      observed at 9.4 +/- 7.3 hours. In return, no correlation was found between the
      increase of plasma creatine-kinase activity, myoglobin and iron or between the
      biochemical markers and time of fibrinolytic therapy. The results confirmed the
      importance of the temporal relationship between lipid peroxidation and iron
      status after thrombolytic therapy. Our results are in agreement with the concept
      that antioxidant agents used in association with thrombolytic therapy might be
      useful.

PMID- 9565781
TI  - Pharmacokinetics of oral artemether in Thai patients with uncomplicated
      falciparum malaria.

PMID- 9565782
TI  - [Adjuvant interferon-alpha therapy of malignant melanoma. Position of the
      Dermatologic Oncology Working Group].

PMID- 9565783
TI  - [Special characteristics of topical treatment in childhood].
AB  - Although the barrier function and thickness of the stratum corneum is fully
      developed in newborns, the infant shows numerous differences in cutaneous and
      systemic metabolism of topically applied substances in comparison to adults. This
      discrepancy between children and adults has been explained by the greater
      systemic availability due to the greater surface area to weight ratio in
      children. Several topically applied drugs such as hexachlorophene, phenol,
      salicylic acid and boric acid in high concentration or on large areas have caused
      toxic reactions and fatalities in infants. Therapeutic approaches to childhood
      dermatoses differ from these used in adults. These age-dependent differences
      concerning the topical application of glucocorticosteroids, urea and dyes are
      described for the treatment of atopic eczema. The development of innovative
      topical drugs may extend therapeutic options especially in children as shown by a
      new topical anesthetic cream improving the treatment of mollusca contagiosa, a
      common childhood problem. Finally, certain physiological differences should be
      considered in newborn and infant skin care.

PMID- 9565784
TI  - [Tissue eosinophilia and local deposition of eosinophil-specific granule
      proteins. Regulation and significance for inflammatory response in atopic
      dermatitis and other inflammatory dermatoses].
AB  - Recent in vitro-studies have substantially increased our knowledge of eosinophil
      activation, the regulation of eosinophilia in the peripheral blood and the role
      of cytokines in that process. Accordingly, chemoattraction and activation of
      eosinophils by cytokines results in the local release of reactive oxygen species
      and toxic cationic granule proteins followed by local propagation of the
      inflammatory reaction and tissue damage. This extracellular tissue deposition of
      toxic granule proteins as an expression of complete activation of eosinophils,
      rather than only the presence of intact eosinophil granulocytes, is crucial for
      their functional effect in situ. Semi-quantitative studies of local eosinophil
      granula deposition so far have been done only in atopic dermatitis and a limited
      number of other inflammatory skin diseases as summarized in this review.
      Evaluation of the pathogenetic role of eosinophils may be of potential
      therapeutic importance.

PMID- 9565785
TI  - [Differentiated contact allergy lists serve in quality improvement].
AB  - Through cooperation between the German Contact Dermatitis Research Group (DKG)
      and the Information Network of Departments of Dermatology (IVDK), results of
      standardized patch tests performed by the participating centres are centrally
      recorded in Germany. For this study, data from 24 departments of dermatology
      (19678 patients) were evaluated retrospectively and separately for 1995 and 1996.
      With decreasing frequency, nickel, fragrance mix, balsam of peru, and thimerosal
      yielded positive reactions most often; surprisingly high numbers of positive
      reactions were also seen with amerchol L-101 and palladium. Differentiated lists
      of allergens were compiled for 1995, referring to subgroups of patients (defined
      by gender, age, localization of eczema, geographical region, occupation,
      sensitization) and particular problems. In men, percentages of positive reactions
      were markedly lower for nickel, fragrance mix and balsam of peru than in women.
      Younger patients reacted more often to thimerosal and older ones to topical
      medical preparations. Medical allergens were also often positive in patients with
      leg eczema, whereas occupational allergens were found more frequently in patients
      with hand eczema. A comparison of positive reactions obtained in distinct
      geographical regions was problematic because of differences between test
      populations. The spectrum of allergens found in office workers was similar to
      that of the whole test population. Patients with positive reactions to nickel and
      fragrance mix had more positive reactions to unrelated allergens than the total
      test population. Sex- and age-adjusted frequencies of sensitization revealed a
      decrease in reactions to nickel and an increase in reactions to mercury allergens
      from 1995 to 1996. The clinical relevance of mercury reactions was often not
      apparent. Differentiated lists of allergens can be used to improve the quality of
      diagnostic and prophylactic procedures in allergic contact dermatitis.

PMID- 9565786
TI  - [Laser and cryotherapy of hemangioma in infants in a direct comparison].
AB  - In our comparative study, 40 infants ranging in age from 1 week to six months,
      were treated for their hemangiomas. Cryosurgery was performed on 20 hemangiomas
      whereas the others were treated with flash lamp-pumped pulsed dye laser (FPDL).
      In 72% of initial macular, flat-topped, superficial hemangiomas a predominant (>
      75%) or complete regression could be achieved. In 68% of cutaneous-exophytic
      lesions, both therapeutical modalities showed a sufficient regression (> 50%) or
      marked growth inhibition after two sessions with further improvement after
      additional treatment. Cutaneous hemangiomas and the cutaneous part of combined
      hemangiomas responded well to both therapies whereas subcutaneous hemangiomas
      were predominantly influenced by cryotherapy. Our data emphasise the efficiency
      of early treatment of childhood hemangiomas. Since FPDL therapy is easy to
      perform, less time-consuming and reduces post-therapeutic exsudation, this
      treatment is preferable in initial macular, flat-topped and superficial lesions
      while cryotherapy is considered to be superior in lesions with marked elevated
      and/or subcutaneous parts.

PMID- 9565787
TI  - [HIV-associated psoriasis. Clinical and histological observations in 36
      patients].
AB  - Between 1982 and 1995, over 700 HIV-infected patients with different skin
      diseases were registered at the Department of Dermatology, Benjamin Franklin
      Medical Center, The Free University of Berlin. Thirty-six of them (approximately
      5%) were diagnosed as having psoriasis. This is clearly a higher prevalence of
      psoriasis than in the general population (1-2%). If psoriasis lesions are not
      clinically seen before diagnosis of HIV infection, the disease will
      preferentially (approximately 80% of these cases) appear during the late stages
      of the infection (CD4/CD8 ratio < 0.4). Six of the 36 patients with HIV-related
      psoriasis (= 16%) were found to have severe disease, showing an exsudative
      clinical picture. In this paper we report in detail on two representative cases
      from this group of patients. Histological examination also revealed exsudative
      changes in HIV-infected patients with clinically moderate psoriasis.
      Immunohistochemically, HIV-related psoriasis showed a moderately decreased number
      of infiltrating T-cells, in contrast to psoriatic skin from non-infected
      patients. A marked difference was the reduced expression of the lymphocyte
      antigen OPD-4 in HIV-related psoriasis. Routine antipsoriatic treatment
      modalities in combination with systemic retinoids and phototherapy (SUP/PUVA)
      were successful in the treatment of severe exsudative psoriasis in HIV patients,
      but the course of the disease was prolonged and exacerbation was more frequent.
      HIV-related psoriasis was found not to influence the underlying HIV infection.

PMID- 9565788
TI  - [Integrated brief psychotherapy in skin diseases. Case contribution with 1-year
      catamnesis].
AB  - The effectiveness of concurrent psychotherapeutic treatment for various skin
      diseases can be regarded as sufficiently validated. Contributions on in-patient
      treatment concepts are rare, and there are up to now no reports on methods
      integrating psychotherapeutic treatment approaches. Our concept of a 4-week short
      term psychotherapy-starting from a conflict hypothesis in the complaint
      intensifying, acute situation-includes the bimodal work on both understanding and
      practice oriented treatment focus. By means of 2 case studies with 1-year-follow
      up, insight is given into the treatment approach from which effective factors of
      psychotherapeutic treatment were tentatively in with patients with skin diseases.

PMID- 9565789
TI  - [Sex-dependent differences in sweating of normal probands and atopic patients in
      cardiovascular stress].
AB  - Sweating (perspiratio sensibillis) due to cholinergic sweat gland activity serves
      predominantly for thermoregulation and is triggered among others by physical
      stress. Individuals suffering from atopic eczema usually respond to sweating with
      generalized itching. Different sweat regulation in atopic patients and healthy
      controls under cholinergic stimulation and heat chamber provocation tests has
      already been examined in several studies. However, no clinical trial has yet been
      done on atopic sweat regulation during physical stress. Sex-specific sweat
      secretion rates have not been evaluated. In our trial we compared sweat amounts
      of male and female atopics (14 m, 10 f) and healthy controls (14 m, 10 f) during
      and after physical activity on a bicycle ergometer. We used a special sweat
      collector system reliable even at intensive body movement. The individual stress
      limit had been determined by previous endurance training with lactate level and
      heart rate measurement. We found a highly significant difference in maximum sweat
      amounts between atopics and controls. On average, healthy individuals (of both
      sexes) perspired nearly three times as much as atopic patients. Male controls
      perspired nearly twice as much as corresponding females. Among the atopics, sex
      specific differences were found to be not statistically relevant.

PMID- 9565790
TI  - [Allopurinol in treatment of cutaneous sarcoidosis].
AB  - Several reports more than ten years ago provided evidence that allopurinol may be
      effective for cutaneous sarcoidosis. We therefore treated two patients with
      histologically confirmed scar sarcoidosis and two with nodular sarcoidosis. A
      daily dosage of 300 mg allopurinol was given over a period of 4-7 months as
      single drug therapy. In both patients with scar sarcoidosis, the skin
      manifestations completely regressed while in the patients with nodular
      sarcoidosis there was significant improvement. The concomittant pulmonary
      involvement in two patients was unpredictable, in one patient improved while the
      other was deteriorated, The mode of action is still unclear but because of the
      positive results and the low rate of side effects, allopurinol seems a reasonable
      agent for treating cutaneous sarcoidosis.

PMID- 9565791
TI  - [Minocycline-induced hyperpigmentation].
AB  - A common adverse effect of minocycline therapy is cutaneous pigmentation. We
      describe two patients who presented with hyperpigmentation caused by minocycline.
      One patient, aged 54 years, had taken minocycline due to lung silicosis for 3
      years before black pigmentation of the face occurred. The other 49 year-old
      patient developed grey-black hyperpigmentation on both lower legs after a 6-month
      therapy with minocycline for folliculitis. This patient was treated with the Q
      switched ruby laser and the pigmentation resolved in the treated area. The
      different clinical and histological forms of minocycline-induced
      hyperpigmentation are discussed.

PMID- 9565793
TI  - [Granulomatosis disciformis Miescher].
AB  - We describe granulomatosis disciformis Miescher in a 57-year old female patient
      with typical clinical manifestation: disc-shaped plaques with slight central
      sclerosis and lesions resembling necrobiosis lipoidica and granuloma anulare.
      Histology revealed an infiltrate mainly composed of macrophages and lymphocytes
      and small foci of necrobiotic collagen and of new collagen formation. We review
      the literature on granulomatosis disciformis and nosology, concluding--as do most
      authors--that granulomatosis disciformis is a characteristic variant within the
      spectrum of cutaneous noninfectious granulomatous disease lying in between
      generalized granuloma anulare and necrobiosis lipoidica.

PMID- 9565792
TI  - [Amantadine-induced livedo reticularis].
AB  - A 63-year old women developed livedo reticularis during treatment with
      amantadine. This reversible side effect of amantadine has been most often seen in
      women and is frequently associated with persistent ankle edema. We discuss the
      signs and symptoms, pathogenesis and treatment of amantadine-induced livedo
      reticularis.

PMID- 9565794
TI  - [World conference on melanoma in Sydney 10-14 June 1997].

PMID- 9565795
TI  - [Malignant melanoma--first workshop in Dresden].

PMID- 9565796
TI  - [Symposium: Recent developments in pathogenesis and therapy of hair diseases 9
      July 1997 in Munich].

PMID- 9565797
TI  - [Allergic rhinitis. An antihistamine with dual effect also reduces obstruction].

PMID- 9565798
TI  - [Pyoderma].

PMID- 9565799
TI  - Improving the appropriateness and effectiveness of ICU practices.

PMID- 9565800
TI  - Refusal of care in the ICU any meaning for doctors?

PMID- 9565802
TI  - Implementation of a clinical practice guideline for stress ulcer prophylaxis
      increases appropriateness and decreases cost of care.
AB  - OBJECTIVE: To develop, implement and evaluate a practice guideline for stress
      ulcer prophylaxis. DESIGN: Before-after study. SETTING: Ten-bed Intensive Care
      Unit (ICU) and 4-bed Step-down Unit in a teaching hospital. PATIENTS AND
      PARTICIPANTS: Fifty patients admitted during 1 year before and 50 patients
      admitted 3-6 months after introduction of the guideline. INTERVENTION:
      Introduction of the practice guideline by dissemination of pocket cards, seminars
      and "academic detailing". MEASUREMENTS AND RESULTS: Appropriateness (defined as
      proportion of days in which the prophylaxis met the criteria in the guideline),
      incidence of gastrointestinal bleeding and of ventilator-associated pneumonia,
      length of stay in ICU and in hospital, ventilator days. ICU mortality and
      medication costs for stress ulcer prophylaxis. After the introduction of the
      guideline, appropriateness increased from 75.8% to 91.1%, and medication costs
      decreased from C $2.50/day to C $1.30/day. There were no differences in any
      clinical outcomes. Predictors of appropriate use or the withholding of
      prophylaxis were the introduction of the guideline, lack of an indication for
      prophylaxis and number of days studied. CONCLUSIONS: Introduction of this
      guideline was associated with an increase in appropriateness of prophylaxis and a
      decrease in medication costs.

PMID- 9565801
TI  - Epidemiology, diagnosis and treatment of systemic Candida infection in surgical
      patients under intensive care.
AB  - The incidence of systemic Candida infections in patients requiring intensive care
      has increased substantially in recent years as a result of a combination of
      factors. More patients with severe underlying disease or immunosuppression from
      anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection
      are now admitted to the ICU. Improvements in supportive medical and surgical care
      have led to many patients who would previously have died as a result of trauma or
      disease surviving to receive intensive care. Moreover, some therapeutic
      interventions used in the ICU, most notably broad-spectrum antibiotics and
      intravascular catheters, are also associated with increased risks of candidiasis.
      Systemic Candida infections are associated with a high morbidity and mortality,
      but remain difficult to diagnose and ICU staff need to be acutely aware of this
      often insidious pathogen. A number of studies have identified risk factors for
      systemic Candida infection which may be used to identify those at highest risk.
      Such patients may be potential candidates for early, presumptive therapy. Here we
      review the epidemiology, pathogenesis, morbidity and mortality of systemic
      Candida infections in the ICU setting, and examine predisposing risk factors.
      Antifungal treatment, including the use of amphotericin B, flucytosine and
      fluconazole, and the roles of early presumptive therapy and prophylaxis, is also
      reviewed.

PMID- 9565803
TI  - Pro-inflammatory cytokine release and mediation of the acute phase protein
      response in fulminant hepatic failure.
AB  - OBJECTIVE: To study the relationship between interleukin-6 (IL-6), tumour
      necrosis factor (TNF) and the acute phase protein C-reactive protein (CRP) in
      patients with fulminant hepatic failure (FHF) and to investigate the potential of
      peripheral blood mononuclear cells (PBMC) isolated from these patients to
      stimulate CRP production by isolated human hepatocytes in vitro. SETTING:
      Patients with FHF were studied at the time of their admission to the intensive
      care unit. STUDY DESIGN: Serum TNF and IL-6 were measured in 12 patients with
      FHF, PBMC from 6 of these patients were then cultured in the presence and absence
      of lipopolysaccharides (LPS). TNF and IL-6 in serum and supernatants were
      measured by ELISA. PBMC supernatants were added to isolated human hepatocytes and
      CRP production was measured. RESULTS: Serum IL-6 (348 +/- 172 pg/ml) and TNF
      (118.5 +/- 15.5 pg/ml) were elevated compared with healthy controls (not
      detected) and these observations were matched by elevated serum CRP in patients
      with FHF (38.9 +/- 7 mg/l). Both the production of IL-6 and TNF by PBMC isolated
      from patients with FHF and the potential of supernatants from these cells to
      stimulate CRP production by hepatocytes in vitro was significantly reduced
      compared with controls. CONCLUSION: Despite the observation that patients with
      FHF have an elevated hepatic acute phase response, PBMC from patients with FHF
      have reduced potential to produce IL-6 and TNF and elicit an acute phase response
      in vitro by the time of patient admission to the intensive care unit. One
      explanation for this observation is early activation and exhaustion of PBMC in
      vivo.

PMID- 9565804
TI  - The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary
      albumin excretion in critically ill patients.
AB  - OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) when given as an
      early treatment to critically ill patients on the serum total anti-oxidant
      potential (TAP) and urine micro-albumin:creatinine (M:Cr) ratio. DESIGN:
      Prospective, placebo controlled double blinded clinical trial. SETTING: General
      intensive care unit in a teaching hospital. PATIENTS: Sixty critically ill
      patients were recruited but ten were withdrawn due to less than 48 h of ICU stay.
      INTERVENTIONS: After envelope randomisation, patients received either NAC (n =
      23): a bolus of 150 mg/kg in 250 ml of 5% dextrose followed by a continuous
      infusion of 12 mg/kg per h in 500 ml of 5% dextrose over 24 h or, as controls (n
      = 27), the equal volume of placebo. Treatment lasted for a minimum of 3, up to a
      maximum of 5, days. Blood and urine samples were collected on admission (0 h) and
      then 6 hourly up 18 h. MEASUREMENTS AND RESULTS: There was no significant
      difference between NAC and placebo groups regarding the required length of
      inotropic support, mechanical ventilation and ICU stay. There was no significant
      difference in TAP or M:Cr ratio over 18 h or between the groups. CONCLUSIONS: Our
      results suggest that NAC had no significant effects on the progress of the TAP
      and the urinary albumin excretion in our patients, which may suggest that NAC at
      the given dose has no clinical relevance as an early treatment in the critically
      ill.

PMID- 9565805
TI  - Cerebral perfusion pressure and intracranial pressure in relation to
      neuropsychological outcome.
AB  - OBJECTIVE: The study attempted to examine the relationship between
      neuropsychological functioning and reduced cerebral perfusion pressure (CPP),
      raised intracranial pressure (ICP), and reduced mean arterial pressure (MAP),
      monitored during intensive care treatment. DESIGN: This prospective follow-up
      study included consecutive patients and evaluated outcome at 6 months postinjury
      by the administration of a neuropsychological test battery. SETTING: The study
      was conducted at the University Hospital of Gent, Belgium. PATIENTS AND
      PARTICIPANTS: Over a 30-month period, 43 patients were included. Inclusion
      criteria were the following: hospital admission following closed head injury. ICP
      monitoring, no medical history of central nervous system disease or mental
      retardation, survival for at least 6 months, and informed consent for
      participation. INTERVENTIONS: All patients received the hospital's standard
      treatment for head injury, which remained unchanged during the study period.
      MEASUREMENTS AND RESULTS: Reduced CPP was analyzed using the number of observed
      values below 70 mmhg, raised ICP using the number of values above 20 mmHg, and
      MAP using the number of values below 80 mmHg. The neuropsychological test battery
      included 11 measures of attention, information processing, motor reaction time,
      memory, learning, visuoconstruction, verbal fluency, and mental flexibility. No
      linear relationships were found between overall neuropsychological impairment and
      episodes of reduced CPP, raised ICP, or reduced MAP. CONCLUSIONS: Although
      reduced CPP and raised ICP are frequent, often fatal, complications of head
      injury, in survivors they do not seem to be related to later neuropsychological
      functioning.

PMID- 9565806
TI  - Pulse oximetry for assessment of pulsus paradoxus: a clinical study in children.
AB  - OBJECTIVE: To evaluate the relationship between intraarterial measured pulsus
      paradoxus (PP) and photoplethysmographic wave changes. SETTING: Tertiary
      pediatric intensive care unit. PATIENTS: 62 nonintubated children with or without
      respiratory disorders. DESIGN: Prospective, clinical study. MEASUREMENTS AND
      RESULTS: Simultaneous paper recordings of photoplethysmographic wave, arterial
      blood pressure, breathing cycle and electrocardiogram. The respiratory dependent
      changes of the plethysmographic respiratory wave (delta pleth, mm) were defined
      as the difference between the highest value of the upper peak of the wave (in
      expiration) and the lowest value of the upper peak (in inspiration). In each
      patient, ten consecutive breaths were averaged for analysis. Five recordings
      could not be evaluated (movement artifacts). In 57 children (median age 2.4
      years, range 7 days to 17 years), the photoplethysmographic fluctuations (delta
      pleth, mm) correlated with PP (mm Hg). r = 0.85; 95% confidence interval (CI),
      0.76 to 0.91. The sensitivity to detect a PP of > 10 mmHg with a plethysmographic
      fluctuation of > 8 mm was 89% (95% CI, 77 to 100%) and the specificity was 90%
      (95% CI, 79 to 100%). CONCLUSIONS: Pulse oximetry appears to be a rapid and
      easily performed, noninvasive method for the objective estimation of the degree
      of PP.

PMID- 9565807
TI  - Severe transient neonatal lactic acidosis during prophylactic zidovudine
      treatment.
AB  - Zidovudine (ZDV) treatment during pregnancy, delivery and the postnatal period is
      effective in reducing the maternal-infant transmission of the human
      immunodeficiency virus. Reported adverse effects in the neonate during this
      longterm treatment are bone marrow suppression and elevation in aspartate
      aminotransferase activity. We report a case of severe ZDV-associated lactic
      acidosis in a neonate, which resolved rapidly following discontinuation of ZDV.
      The mechanisms leading to this side effect are poorly understood.

PMID- 9565809
TI  - Prediction of outcome after resuscitation in a case of electrocution.
AB  - Electrical shocks commonly cause widespread acute and delayed tissue damage.
      Cardiac arrhythmias and respiratory arrest are the most life-threatening
      complications in the acute phase. Prediction of outcome after cardiopulmonary
      resuscitation is usually based on neurological findings compatible with anoxic
      encephalopathy. This report describes a case of electrocution followed by
      cardiopulmonary resuscitation. Although neurological signs on admission pointed
      towards severe brain injury, the patient fully recovered and was able to resume
      the level of cognitive functioning prior to the accident.

PMID- 9565808
TI  - Heart transplantation without informed consent: discussion of a case.
AB  - OBJECTIVE: To discuss informed consent to heart transplantation in the case of an
      intensive care unit (ICU) patient: relatives' informed consent was refused by the
      patient himself whose cognitive ability appeared to be reasonable for the
      purpose. SETTING: ICU of a university teaching hospital. PATIENT: A 62-year-old
      man who underwent myocardial revascularization had in the immediate post
      operative hemodynamic instability, continuous serious arrhythmias, ventilatory
      support, fentanyl infusion. Heart transplantation could be the only chance for
      his survival. INVENTION: Heart transplantation. RESULTS: Despite patient's
      refusal, we decided to hold the relative's consent as valid, and transplantation
      was accordingly performed, to the subsequent satisfaction of the patient.
      CONCLUSIONS: Our decision was based on two beliefs: (1) the severity of the
      patient's clinical condition may have impaired his cognitive abilities; (2) the
      very same conditions may mask impairment and certainly make reliable assessment
      of cognition and judgment impossible. This being so, the preservation of life
      assumes priority.

PMID- 9565810
TI  - Fibrinolytic changes in a patient with toxic shock syndrome; release of active u
      PA.
AB  - OBJECTIVE: Definition of the changes in the activators of plasminogen, u-PA and t
      PA, and examination of the possible generation of plasmin in the circulation in
      overwhelming sepsis. DESIGN: Serial blood analysis starting 4 h after development
      of symptoms of toxic shock syndrome. SETTING: Intensive care unit. PATIENT: A
      previously healthy woman underwent endometrial ablation and rapidly thereafter
      developed staphylococcal toxic shock syndrome with organ failure. MEASUREMENT AND
      RESULT: t-PA, PAI-1, t-PA-PAI-1 complexes, plasminogen, fibrinogen and plasmin
      alpha 2-antiplasmin complexes were measured serially by ELISA and free u-PA by
      SDS-PAGE with zymography. The onset of symptoms was accompanied by a rise of t-PA
      antigen-followed rapidly by PAI-1 antigen. Plasmin-alpha 2-antiplasmin complex
      was generated in large amounts but disappeared within hours. From day 3, free u
      PA was detectable in the circulation without plasmin generation. CONCLUSION:
      Despite the sustained presence of active u-PA in the circulation and of t-PA
      antigen at the onset of symptoms, plasmin-alpha 2-antiplasmin generation was
      largely suppressed by high levels of PAI-1. The suppression of plasmin generation
      by u-PA and t-PA may ensure the persistence of fibrin in the microcirculation and
      so contribute to organ failure.

PMID- 9565811
TI  - Continuous venovenous hemodiafiltration (CVVHDF) with citrate anticoagulation in
      the treatment of a patient with acute renal failure, hypercalcemia, and
      thrombocytopenia.
AB  - A 72-year-old patient with multiple myeloma was admitted to the intensive care
      unit because of hypercalcemic crisis and acute renal failure. After 7 days of
      comprehensive therapy including diuretics steroids, calcitonin, and intermittent
      hemodialysis (IHD) with low-calcium dialysate, calcium still reached high levels
      between IHD treatments and thrombocytopenia developed after chemotherapy. CVVHDF
      with calcium-free bicarbonate dialysate was started. Anticoagulation with 2.2%
      citrate was performed in order to chelate calcium, and thus treat the
      hypercalcemia, and to provide regional anticoagulation, and thus reduce the risk
      of bleeding due to thrombocytopenia. CVVHDF with citrate anticoagulation was
      continued for 6 days, and standard heparin anticoagulation was started when the
      hypercalcemia and thrombocytopenia abated.

PMID- 9565812
TI  - Acute respiratory failure caused by secondary alveolar proteinosis in a patient
      with acute myeloid leukemia: a case report.
AB  - Pulmonary alvelolar proteinosis (PAP) is a rare cause of chronic respiratory
      failure due to progressive alveolar accumulation of a periodic acid-schiff (PAS)
      positive proteinaceous material. In some cases, the rapid accumulation of intra
      alveolar material leads to acute respiratory failure (ARF). We report the
      causative role of secondary PAP in the case of a 26-year-old man with acute
      myeloid leukemia who developed fever, increased serum lactate dehydrogenase level
      and ARF, and required mechanical ventilation. The diagnosis of PAP was
      established by the examination of material obtained by bronchoalveolar lavage
      (BAL). Respiratory improvement occurred several days after the patient had
      recovered from neutropenia. This report underlines the importance of the early
      diagnosis of PAP as a potential cause of ARF in leukemic patients. Adequate stain
      on BAL fluid provides the diagnosis and avoids repeated invasive procedures and
      inappropriate treatments.

PMID- 9565814
TI  - Two unusual complications of prone-dependency in severe ARDS.

PMID- 9565815
TI  - Major reduction in alarm frequency with a new pulse oximeter.

PMID- 9565813
TI  - Markers of cellular dysoxia during orthotopic liver transplantation in pigs.
AB  - OBJECTIVE: To characterize global, regional, and end-organ markers of cellular
      dysoxia during orthotopic liver transplantation and early reperfusion in pigs.
      DESIGN: Descriptive study. SETTING: University hospital research laboratory.
      ANIMALS AND INTERVENTIONS: 7 fasted, anesthetized, and mechanically ventilated
      Yorkshire pigs underwent orthotopic liver transplantation. Oxygen consumption
      (VO2) and oxygen delivery (DO2) were both calculated using standard formulae.
      Gastric interstitial pH and the gastroarterial partial pressure of carbon dioxide
      (PCO2) gradient were measured with a gastric tonometer. The following were
      determined from arterial blood samples: serum lactate to pyruvate ratio, serum 3
      hydroxybutyrate to acetoacetate ratio, plasma free fatty acids, and plasma free
      and total carnitine levels. MEASUREMENTS AND RESULTS: Data were collected 1 h
      after induction of anesthesia (I), at the end of the anhepatic phase (A), and 1 h
      after reperfusion (R), Median (range) VO2 values obtained at the specified time
      points were: I 318 (206-1860), A 210 (152-408), R 330 (214-424) ml/kg per min,
      respectively (NS); DO2 values were: I 1828 (1382-3259), A 1219 (452-2492), R 1741
      (1345-12,071) ml/kg per min, respectively (NS). The lactate to pyruvate ratio,
      reflecting the redox potential of the cytosol, progressively increased: I 22 (9
      46), A 29 (16-68), R 43 (23-55), (p < 0.05). Gastric interstitial pH, as well as
      the gastroarterial PCO2 gradient values at the specified time points did not
      reach statistical significance. Levels of ketone bodies (3
      hydroxybutyrate+acetoacetate) remained lower than 0.120 mmol/l. The ketone body
      ratio did not significantly vary over time (NS). Plasma esterified and free
      carnitine concentrations and free fatty acid values remained within normal limits
      (NS). Among these markers, the ketone body ratio presented the largest area under
      the receiver operating characteristic curve as a marker of postoperative
      mortality, with an inflexion point at 0.9. CONCLUSION: In this study, orthotopic
      liver transplantation was associated with significant variations over time in the
      redox potential of the cytosol. Postoperative mortality was, however, related to
      the redox state of the liver mitochondria. Our data suggest the occurrence of
      abnormal tissue oxygenation during liver transplantation.

PMID- 9565816
TI  - Continuous syringe pumps.

PMID- 9565817
TI  - Peristomal infection after translaryngeal tracheostomy: a risk linked to the
      colonization of the oropharynx?

PMID- 9565818
TI  - Hypercarbia during tracheostomy.

PMID- 9565820
TI  - Optimization of patient-ventilator interactions.

PMID- 9565819
TI  - Gastrointestinal permeability following cardiopulmonary bypass.

PMID- 9565821
TI  - Effects of long-term oral beta-carotene supplementation on lipid peroxidation in
      patients with cystic fibrosis.
AB  - The aim of this study was to determine the efficacy of oral beta-carotene
      supplementation for the correction of an oxidant-antioxidant imbalance in cystic
      fibrosis (CF). We studied 24-patients with cystic fibrosis and 14 healthy
      controls. 13 CF-patients were allocated to a CF-supplementation group, which
      received 1 mg beta-carotene/kg BW/d up to a body weight (BW) of 50 kg, patients
      with a BW greater 50 kg received 50 mg beta-carotene/d for 12 weeks. For the
      following 12 weeks all patients of the CF-supplementation group were treated with
      10 mg beta-carotene/d. Placebos with starch were applied to 11 CF-patients.
      Baseline plasma beta-carotene concentrations of CF patients (mean +/- SD, 0.08 +/
      0.04 mumol/l) were significantly lower than those of age-matched controls (o.3
      +/- 0.1 mumol/l) (p < 0.001). beta-carotene concentrations of the CF
      supplementation group increased rapidly and reached a value of 0.6 mumol/l after
      12 weeks of supplementation. Normal values were measured for plasma ascorbate and
      alpha-tocopherol. Plasma retinol concentrations were in the lower normal range
      and did not increase during supplementation. Total antioxidative capacity in
      plasma of the CF-supplementation group increased after 12 weeks of
      supplementation at an extent of 12%. Positive influence was indicated by a
      decrease of plasma malondialdehyde. Thus oral beta-carotene supplementation is
      effective in normalizing status of beta-carotene and malondialdehyde in CF
      patients.

PMID- 9565822
TI  - Continuous of "pulse-and-withdraw" supply of ascorbic acid in the diet: a new
      approach to altering the bioavailability of ascorbic acid, using teleost fish as
      a scurvy-prone model.
AB  - In scurvy-prone animals ascorbic acid uptake is regulated by the number of
      intestinal "brush-border" carriers available for transport. The number of
      carriers is negatively affected by an increasing dietary ascorbic acid intake,
      thus limiting the maximum attainable uptake. We tested a new approach towards
      manipulating the accumulation of ascorbic acid in rainbow trout by repeatedly
      feeding a 10 day ascorbic acid allowance in a 1 or 3 day "pulse" followed by
      withdrawal, rather than spread out over the entire 10 day period. Pulse dosing
      led to initially increased mortalities compared to continuous dosing, but this
      was reversed after 55 days. Although individual weight and cumulative mortality
      were not significantly different after 88 days, total liver ascorbic acid levels
      were significantly higher in the 1-day pulse group (16.3 +/- 3.9 micrograms/g)
      than in the 3-day pulse (9.8 +/- 0.9 micrograms/g) or continuous (9.3 +/- 0.9
      micrograms/g) groups. This led us to conclude that after an initial adaptation
      phase a feeding profile with intermittent ascorbic acid withdrawal results in a
      compensatory increase in uptake of ascorbic acid from the diet and/or a better
      conservation of the body pool of ascorbic acid, opening interesting new avenues
      for ascorbic acid dosing and therapy.

PMID- 9565823
TI  - Serum C3 content in vitamin B(12)-deficient rats.
AB  - As a clue to clarifying the role of vitamin B12 (B12) in the function of the
      complement system, serum C3 content was determined in B12-deficient rats, and the
      effect of the administration of methylcobalamin (CH3-B12) on the serum C3 content
      was also studied. It was found that the serum C3 content in rats fed on a vitamin
      B12-deficient diet for 90 and 120 days significantly decreased compared with that
      in control rats. The administration of CH3-B12) restored the serum C3 content to
      control levels. The above results indicate that B12-deficiency depressed the
      serum C3 content and lowered humoral immunocompetence, and that these changes
      were ascribable to B12-deficiency.

PMID- 9565824
TI  - Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations
      in healthy young women.
AB  - Elevated plasma homocysteine levels are a risk factor for atherosclerotic
      disease. Elevated fasting plasma homocysteine concentrations can be reduced by
      vitamin supplementation with folic acid, vitamin B6 and vitamin B12, but the
      effect of nutritive amounts of single vitamins on homocysteine plasma levels
      within the normal range is not known. This study was performed to investigate the
      effect of folic acid supplementation (400 micrograms/d) on fasting plasma
      homocysteine levels in healthy young women, in comparison to vitamin B6 (2 mg/d)
      or a combination of both vitamins. Healthy young women with normal homocysteine
      levels were supplemented for four weeks either with folic acid, vitamin B6 or the
      combination. The combination of folic acid and vitamin B6 reduced plasma
      homocysteine by 17%. Supplementation with folic acid reduced plasma homocysteine
      levels by 11.5%. The effect of folic acid and vitamin B6 was not significantly
      different from the effect of folic acid alone. Vitamin B6 had no effect on plasma
      homocysteine concentrations. Results show that homocysteine levels within the
      normal range are lowered by low-dose vitamin supplementation including folic
      acid.

PMID- 9565825
TI  - NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa
      by rat hepatocytes--effect of clofibrate-feeding.
AB  - NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa
      by rat hepatocytes was investigated. In the control hepatocytes, NAD+ synthesis
      from tryptophan was not affected by nicotinic acid from 0.026 to 0.26 mM. NAD+
      synthesis from nicotinic acid was slightly inhibited with varying concentrations
      of tryptophan from 0.1 to 1.0 mM. In the clofibrate-treated hepatocytes, NAD+
      synthesis from tryptophan was greatly increased (234% of the control), while that
      from nicotinic acid was decreased (71.2% of the control). Both, NAD+ synthesis
      from tryptophan and that from nicotinic acid were decreased by the coexisting
      nicotinic acid or tryptophan. Total amount of NAD+ synthesized from tryptophan
      and nicotinic acid at their physiological concentrations was significantly higher
      than that in the control hepatocytes as a result of a large increase of NAD+
      synthesized from tryptophan. When the metabolic flux of 0.1 or 0.5mM tryptophan
      was investigated, the glutarate pathway was suppressed in the clofibrate-treated
      hepatocytes, the quinolinic acid-NAD+ flux being elevated. Similarly to
      clofibrate, DEHP and CPP revealed an increase in NAD+ synthesis from tryptophan.
      Mutual relationship of NAD+ biosyntheses from tryptophan and nicotinic acid in
      rat hepatocytes is discussed and the relevance with peroxisomal proliferation is
      suggested.

PMID- 9565826
TI  - Relative bioavailability of coenzyme Q10 formulations in human subjects.
AB  - The relative bioavailability of typical commercially available forms of coenzyme
      Q10 (CoQ10) was compared with that of Q-Gel, a new solubilized form of CoQ10, in
      human subjects in two separate trials. In the first, standard softgel capsules
      containing CoQ10 suspension in oil, powder-filled hardshell capsules and powder
      based tablets were tested along with Q-Gel using a daily dosage of 120 mg for
      three weeks. The baseline plasma CoQ10 values were all very tight (0.50-0.52
      microgram/mL) and after three weeks the values were 1.37, 1.63 and 1.60
      micrograms/mL for the first three products and 3.31 micrograms/mL for Q-Gel. The
      relative bioavailability calculated using the areas under the plasma CoQ10 curve
      (AUC) were (micrograms/mL x time in days) 7.16 (100%), 8.97 (125%), 9.19 (128%)
      and for Q-Gel 22.86 (319%). The second trial, carried out to replicate the
      findings in the first, employed only two groups, namely the standard softgel
      capsules containing the suspension and Q-Gel, and the duration was extended to
      four weeks. Plasma CoQ10 values were: baseline 0.40 and 0.38 and after four weeks
      1.26 and 2.80; the corresponding AUCs were: 8.33 (100%) and 22.75 (273%). Thus,
      the data from both the trials show that Q-Gel, the new solubilized form of CoQ10,
      is vastly superior to typical commercially available preparations of CoQ10. This
      means much lower doses of Q-Gel will be required to rapidly reach and maintain
      adequate blood CoQ10 values than with any of the other currently available
      products.

PMID- 9565827
TI  - Modulation of select immune responses by dietary capsaicin.
AB  - Capsaicin (CAP) is the spicy principle of hot peppers that has been used as a
      food additive, preservative, and medicine. In this study, we investigated the
      effect of dietary CAP on immune status and selected immune responses. BALB/c mice
      were divided into 5 groups and fed diets with either 0, 5, 20, 50 or 100 ppm CAP
      for 3 weeks. The parameters measured with lymphocytes included mitogen-induced
      proliferation, plaque-forming cell number, and total serum immunoglobulin levels.
      In spleen cells of mice fed 20 ppm CAP there was a greater T-cell mitogen
      induced, lymphocyte proliferative response. In addition, the number of antibody
      producing B cells and serum IgG and IgM levels increased in mice fed 20 ppm CAP
      as compared to the control with no CAP. The effect of dietary CAP on macrophage
      activity was assessed by phagocytosis and tumor necrosis factor-alpha (TNF alpha)
      production. Dietary CAP had no effect on phagocytic activity by peritoneal
      macrophages, but the levels of secreted TNF alpha increased in the groups fed 20
      ppm CAP compared to the control. These results suggest that dietary CAP may
      differentially enhance immune status as well as select immune functions. That is
      in contrast with previous studies that show immunosuppression observed after CAP
      injection.

PMID- 9565828
TI  - Difference in the breakfast habits of overweight/obese and normal weight
      schoolchildren.
AB  - The aim of the present study was to analyse the differences between the breakfast
      habits of obese/overweight (O) (those with body mass index [BMI] above the 75th
      percentile) and normal weight schoolchildren (N) (those with BMI equal to or
      below the 75th percentile). A seven consecutive days "food record" was used to
      record the intake of foods at breakfast and throughout the rest of the day. O
      subjects, and in particular female O subjects, omitted breakfast more frequently
      and took significantly smaller quantities of cereals than did N subjects. The
      energy supplied by breakfast, measured as a percentage of energy expenditure, was
      significantly lower in O subjects (17.0 +/- 8.5% in males and 14.6 +/- 6.1% in
      females) than in N subjects (20.9 +/- 9.4% in males and 17.6 +/- 6.5% in
      females). With respect to the energy and nutrients supplied by breakfast, O
      subjects took lower quantities of carbohydrates, thiamin, niacin, pyridoxine,
      vitamin D and iron than did N subjects. The energy profiles of O subjects
      breakfasts were more imbalanced than those of N subjects. A significant
      difference was seen between the amounts of energy supplied by carbohydrates.
      Without doubt, O subjects have less satisfactory breakfast habits than N
      subjects. This might be a reflection of whole diet that is less adequate,
      however, it is possible that an inadequate breakfast contributes to the making of
      poor food choices over the rest of the day, and, in the long term, to an
      increased risk of obesity.

PMID- 9565829
TI  - Ageing, nutritional status and immune response.
AB  - The effects of vitamin supplementation on the age-related decline in immune
      function was studied in a population of elderly subjects with a high prevalence
      of low and deficient serum values of vitamin C, vitamin E, riboflavin and
      pyridoxin, as well as iron and zinc. The immune function was examined by
      measuring delayed cutaneous hypersensitivity (DCH) after intradermal application
      of a set of 7 antigens in 72 subjects aged 60-89 years living in two homes for
      the elderly. The results showed an almost linear statistically significant
      decline in the DCH test with age (p < 0.01). Vitamin supplementation for a period
      of 10 weeks significantly improved the biochemical parameters for those vitamins
      and the age related decline in the DCH test was no longer statistically
      significant (P > 0.05). No statistically significant changes in DCH were observed
      in the placebo group. The results of this study suggest that nutrition may be an
      important determinant of immunocompetence in the elderly.

PMID- 9565830
TI  - The effects of fasting and refeeding healthy volunteers on serum folate levels.
AB  - Fasting serum folate levels are commonly used in assessing folate status and also
      in estimating the bioavailability of synthetic folic acid and food folate.
      Previous work has shown that serum folate more than doubles in concentration
      during a 48 hour fast. Following a 24-hour standardisation procedure, serum and
      urinary folate levels were measured in nine healthy female volunteers fasting for
      36 hours and in the first 6 hours during refeeding. Serum folate concentration
      increased from a mean of 14.8 ng/ml to 29.3 ng/ml during the 36 hour fast and
      fell to 22.1 ng/ml during the 6 hour refeeding period. The rise in serum folate
      concentration during the fast was negatively related to serum folate
      concentration at 0 hours fasting. It is hypothesised that the enterohepatic
      recirculation of folate plays an important role in the underlying physiological
      mechanism. These findings highlight the need to standardise energy intake to
      control for hepatic influences on folate metabolism in future studies assessing
      the bioavailability of folate in food.

PMID- 9565831
TI  - Effect of beta-sitosterol on ultrastructure of liver cells in young and aged
      mice.
AB  - The effects of beta-sitosterol on liver ultrastructure were studied using young
      and aged male mice. Both groups of mice were fed a beta-sitosterol or a control
      diet. The beta-sitosterol diet contained 1% beta-sitosterol. Ultrastructural
      differences in the liver cells were evident between two groups fed the two diets.
      The number of peroxisomes was significantly greater in the liver cells of both
      young and aged mice fed the beta-sitosterol diet than in those fed the control
      diet. There were also significant differences in the maximum length of lipid
      droplets between the young and aged mice fed the beta-sitosterol diet. These
      results suggest that beta-sitosterol affects liver ultrastructure, and that some
      ultrastructural differences in liver cells exist between young and aged mice fed
      the beta-sitosterol diets.

PMID- 9565832
TI  - Gustatory and food habit changes during the menstrual cycle.
AB  - Gustatory and food habit changes during the menstrual cycle were studied in 8
      women, 6 smokers and 2 non-smokers, aged 23-37 years. The following parameters
      were evaluated during three consecutive menstrual cycles: blood oestradiol and
      progesterone levels on the 7th, 14th and 21st day of each cycle
      (radioimmunoassay); detection and recognition thresholds and concentration
      preferences for sucrose, sodium chloride, citric acid and quinine sulphate on the
      1st, 7th, 14th and 21st day of each cycle; food consumption (weighed record) on
      days 1 and 2, 6-8, 13-15 and 20-22 each cycle. The four basic tastes were
      influenced differently by blood hormone levels during the menstrual cycle.
      Sensitivity to sweet taste increased with an increase of oestradiol, while
      sensitivity to bitter taste increased with an increase of progesterone. No
      correlations between hormone levels and acid taste, and only a few correlations
      for salt taste were found. Food habits changed during the cycle particularly for
      meat and fruit. Vegetables and cereals showed only a tendency to vary. In
      correspondence with the highest oestradiol values there was a tendency towards
      lower energy intake, -122 kcal (-0.51 MJ) = 8%, predominantly provided by
      carbohydrates (as bread).

PMID- 9565834
TI  - Computed tomography in the elderly.

PMID- 9565833
TI  - Pernicious anemia and reversible dementia: Strachan and Henderson 30 years later.

PMID- 9565835
TI  - Late-life depression in private practice depressed outpatients: a 203-case study.
AB  - OBJECTIVE: To establish the prevalence of late-life depression in
      unipolar/bipolar depressed outpatients in private practice, to compare it with
      depression in younger patients and to compare its early/late-onset subtypes.
      METHODS: Two hundred and three consecutive unipolar/bipolar depressed outpatients
      presenting for treatment of depression were interviewed with the Comprehensive
      Assessment of Symptoms and History structured interview and depression severity
      was assessed with the Montgomery and Asberg Depression Rating Scale and the
      Global Assessment of Functioning Scale. RESULTS: Prevalence was 21%. Late-life
      depression had significantly more unipolar/fewer bipolar patients, higher age at
      onset, longer duration of illness and lower psychiatric comorbidity than
      depression in younger patients. Severity, psychosis, chronicity and recurrences
      were not significantly different. Early-onset late-life depression had
      significantly lower age at baseline, longer duration of illness and more
      recurrences than late-life depression. CONCLUSIONS: Findings support suggested
      age subdivisions of depression and provide a picture of private practice late
      life depression.

PMID- 9565836
TI  - Can staff training reduce behavioural problems in residential care for the
      elderly mentally ill?
AB  - The effect of a brief in-service training programme on the psychosocial
      management of behavioural disturbance in residential care is described. Although
      the incidence of problematic behaviour did not change 3 months after training,
      staff in the experimental homes reported a significant improvement in their
      management of problematic behaviour, as compared to the control home. However,
      these effects were not maintained a year later. The importance of post-training
      supervision and the sociocultural context of the home in the maintenance of
      psychosocial intervention in residential settings is discussed.

PMID- 9565837
TI  - The role of the old age psychiatry consultation liaison nurse.
AB  - OBJECTIVE: To assess and describe service changes when a psychiatric consultation
      liaison nursing service is introduced. DESIGN: Prospective collection of basic
      service data before and after implementation of the service change. SETTING: A
      newly established comprehensive old age psychiatry service. PATIENTS: People on
      medical and surgical wards aged over 65 years referred for psychiatric
      assessment. OUTCOME MEASURES: Numbers of referrals made and patients seen,
      details of psychiatric diagnoses made and follow-up offered before and after the
      change in the service. RESULTS: Within 6 months there was an increase in liaison
      referrals to the service. The proportion of people offered follow-up showed
      little change and delay before assessment decreased substantially with the PCLN
      service. CONCLUSIONS: A psychiatric consultation liaison nursing (PCLN) service
      was successfully initiated. Numerous difficulties were encountered but this is a
      useful model for old age psychiatry services to consider researching and
      developing further.

PMID- 9565838
TI  - Lithium in the over-65s: who is taking it and who is monitoring it? A survey of
      older adults on lithium in the Cambridge Mental Health Services catchment area.
AB  - OBJECTIVES: To determine the prevalence of lithium therapy in the over-65s in the
      Cambridge Mental Health Services catchment area, to obtain a profile of this
      group and to find out how well and by whom lithium treatment is being monitored.
      METHODS: A census was carried out of patients over the age of 65 in the Cambridge
      Mental Health Services catchment area who were on lithium therapy on 1 February
      1995. The records of these patients were examined retrospectively for demographic
      details, details of lithium therapy, information about lithium monitoring and
      risk factors associated with lithium treatment. RESULTS: One hundred and forty
      eight patients were identified representing a point prevalence of 0.27%. GPs
      carried out lithium monitoring for the majority of this group and 47% had not
      been seen by a psychiatrist in the 12 months leading up to the census date.
      Thirty-two per cent of the group were on thyroxine treatment or had raised TSH
      levels. CONCLUSIONS: The prevalence of lithium therapy in this study was greater
      than the prevalences reported in studies of patients of all ages. Standards of
      monitoring varied widely and were not always better where psychiatrists monitored
      the treatment, although psychiatrists were more likely than GPs to monitor renal
      function. There was a high rate of thyroid dysfunction in the study group.

PMID- 9565839
TI  - The recognition and treatment of depression in older people in primary care.
AB  - OBJECTIVES: To examine general practitioners' (GP) awareness of depression in
      their elderly patients (aged over 65) and to identify characteristics of those
      patients least likely to be recognized and treated. DESIGN: A cross-sectional
      study comparing the clinical opinion of the GP with assessment of mental state
      using a validated interview schedule (the Short Comprehensive Assessment and
      Referral Evaluation). SETTING AND SUBJECTS: 510 elderly residents in the Gospel
      Oak area of Camden in North London registered with 28 GPs at 13 practices. MAIN
      OUTCOME MEASURES: Agreement between GP view and patients interview. Evidence of
      active management measured by examining GP records for appointments, referrals
      and prescription of psychotropic mediation. RESULTS: GPs were aware of depression
      in 36 (51%) of 70 depressed patients. Those least likely to be recognized were
      men, the married, those with high levels of physical handicap, those suffering
      from visual impairment and those who were least well educated. Of the 32 patients
      believed to be depressed, 12 (38%) were prescribed antidepressant medication
      and/or referred to mental health/social services. CONCLUSIONS: Levels of
      recognition of depression were lower than other recent reports. These findings
      may reflect the continued debate about the most suitable management of the
      elderly depressed in primary care and stress the need for further evaluation of
      appropriate treatment strategies for this group.

PMID- 9565840
TI  - Effect of apolipoprotein E status on clinical features of dementia.
AB  - OBJECTIVE: The aims of this study were (a) to determine the frequency of APOE
      genotypes in dementia, (b) to relate e4 allele frequency to clinical
      symptomatology of dementia and (c) to relate e4 and assess risk factors for
      different types of dementia. DESIGN: Prospective clinical study setting older
      patients with dementia known to a community-based old age psychiatry service.
      SAMPLE: 101 patients fulfilling ICD 10 criteria for dementia. RESULTS:
      Replication of previous findings of an association between APOE4 and Alzheimer's
      disease: younger age of onset of dementia; family history of dementia;
      persecutory ideation; and (retrospectively determined) rate of competent decline.
      No association was found between APOE4 and vascular dementia. The association
      between APOE4 and 'mixed dementia' was intermediate between that of pure
      Alzheimer's disease and pure vascular dementia. CONCLUSION: The results confirm
      the relationship between clinical features of dementia and APOE4 status. It may
      be that APOE can be used as an adjunct to clinical diagnosis.

PMID- 9565841
TI  - Be aware of the second revolution: the need to expand the market for infertility
      services and how to do it.

PMID- 9565842
TI  - The uterus: idiot savant or Rosetta Stone?

PMID- 9565843
TI  - Embryo quality and endometrial receptivity: lessons learned from the ART
      experience.

PMID- 9565844
TI  - To what extent does endometrial receptivity influence the outcome of assisted
      reproductive technology?

PMID- 9565845
TI  - Commonality within diversity: the plasma membrane transformation of uterine
      epithelial cells during early placentation.

PMID- 9565846
TI  - What is a preclinical pregnancy loss?
AB  - PURPOSE: To evaluate the contribution of embryo quality to preclinical loss rates
      after in vitro fertilization (IVF)/embryo transfer (ET) pregnancy, multiple
      gestation, and clinical loss rates were compared to preclinical pregnancy loss
      rates over a 3-year period. METHODS: The pregnancy outcomes after 1675 fresh ETs
      from 1994 to 1997 were studied. While establishment of a clinical pregnancy
      confirms uterine receptivity, multiple gestation rates reflect embryo quality.
      Because the majority of clinical losses are chromosomally abnormal, clinical loss
      rates serve as another indicator of embryo quality. RESULTS: The overall
      preclinical pregnancy loss rate was 5% (78/1675) of ETs and 17% (78/472) of
      pregnancies. During the 3-year period the pregnancy rates per ET increased from
      19 to 36% (P < 0.0001), multiple gestation rates increased from 21 to 48% (P <
      0.008), clinical loss rates decreased from 20 to 6% (P < 0.0001), and preclinical
      pregnancy loss rates remained unchanged from 13 to 19% (P = 0.1). CONCLUSIONS:
      Preclinical pregnancy loss more likely reflects abnormalities in uterine
      receptivity rather than embryo quality. If recurrent preclinical pregnancy loss
      occurs after IVF/ET, evaluation for abnormalities of uterine receptivity should
      be performed.

PMID- 9565847
TI  - Relationship between creatine kinase levels and clinical diagnosis of
      infertility.
AB  - PURPOSE: The creatine kinase level indicates sperm maturity and correlates with
      the spermatozoal fertilizing potential. The relationship between creatine kinase
      levels in subfertile men and their clinical diagnosis was examined. METHODS:
      Patients with unexplained infertility (n = 34), varicocele (n = 20),
      postvasectomy reversal (n = 7), or cancer (n = 22) were included in this
      prospective clinical study. The control group consisted of healthy normal donors
      (n = 15). RESULTS: The median and interquartile range values of creatine kinase
      for each group were as follows: normal donors, 0.061 U/10(8) sperm (0.056 to
      0.076 U/10(8) sperm); idiopathic male factor, 0.119 U/10(8) sperm (0.061 to 0.190
      U/10(8) sperm); varicocele, 0.392 U/10(8) sperm (0.209 to 1.494 U/10(8) sperm);
      postvasectomy reversal, 0.589 U/10(8) sperm (0.425 to 4.043 U/10(8) sperm); and
      cancer, 0.068 U/10(8) sperm (0.047 to 0.168 U/10(8) sperm). Sperm creatine kinase
      levels were significantly higher in patients with varicocele compared to normal
      donors (P = 0.0001), cancer patients (P = 0.0002), and men with idiopathic
      infertility (P = 0.0009). Sperm concentration and creatine kinase level were
      inversely correlated in patients (r = -0.7, P < 0.001) but not in normal donors.
      CONCLUSIONS: Semen quality is poorer in subfertile patients with clinical
      varicocele and postvasectomy reversal than in cancer patients and patients with
      idiopathic male infertility. That the creatine kinase levels in cancer patients
      were similar to those of normal donors suggests that the final phase of
      spermatogenesis may not be altered in men with cancer; thus semen from these
      patients should be banked to ensure fertility after cancer treatment.

PMID- 9565849
TI  - Contamination of embryo transfer catheter and treatment outcome in in vitro
      fertilization.
AB  - PURPOSE: The effect of embryo transfer (ET) catheter contamination with mucus
      and/or blood on treatment outcome in an in vitro fertilization (IVF) program was
      evaluated. METHODS: One thousand four ET procedures in 877 patients having
      conventional IVF in the long (1189 cycle) and short (15 cycles) protocol were
      analyzed to determine the impact of catheter contamination on the incidence of
      retained embryos and the clinical pregnancy rate. RESULTS: Catheter contamination
      with mucus and/or blood is a feature of difficult ET. Embryos were significantly
      more likely to be retained when the transfer catheter was contaminated with mucus
      (17.8 versus 3.3%) or blood (12 versus 3.3%). When the catheter was contaminated
      and an embryo(s) was retained and immediately retransferred, the pregnancy rate
      was not compromised. The pregnancy rate was significantly reduced when the ET
      catheter was contaminated with blood (15.5 versus 27.1%; P = 0.002), but no
      embryo was retained in the catheter set. CONCLUSIONS: Catheter contamination
      compromises the treatment outcome in IVF only when there is no associated
      retained embryo(s). As increased vigilance in searching for extruded embryos may
      not be practical, we suggest that cervical mucus should be routinely aspirated
      and ET performed as atraumatically as possible.

PMID- 9565848
TI  - Effects of endometriomas on ooccyte quality, embryo quality, and pregnancy rates
      in in vitro fertilization cycles: a prospective, case-controlled study.
AB  - PURPOSE: The effect of endometriomas on oocyte quality, embryo quality, and
      pregnancy rates in in vitro fertilization (IVF) cycles was evaluated. METHODS:
      Forty-five women had "chocolate" cysts aspirated at the time of oocyte retrieval,
      and cyst fluid CA 125 levels were measured to ascertain presence of "true"
      endometriomas. Fifty-seven women without any complex cysts at the time of oocyte
      retrieval served as controls. IVF cycle outcome parameters were compared between
      the two groups. RESULTS: Women with endometriomas experienced a significantly
      higher rate of early pregnancy loss compared to controls (47 vs 14%). There was
      also a trend toward fewer oocytes retrieved and fewer embryos reaching at least
      the four-cell stage 48 hr after retrieval in patients with true endometriomas vs
      controls. CONCLUSIONS: The presence of endometriomas at the time of oocyte
      retrieval is associated with increased rates of early pregnancy losses. The
      number of oocytes retrieved and the embryo quality may also be affected adversely
      in the presence of endometriomas.

PMID- 9565851
TI  - The influence of advanced age on the outcome of assisted reproduction.
AB  - PURPOSE: Our purpose was to determine the influence of age on the outcome of
      assisted reproduction, with particular interest in women aged 40 years or older.
      METHODS: A retrospective review of the 779 patients enrolled in the Royal
      Hospital for Women Fertility Group fertility program between 1987 and 1994 was
      performed. The results for women aged 40 years or older were compared with those
      for women between 36 and 39 years and those younger than 36 years. The main
      outcome measures were pregnancy rate, pregnancy outcome, fertilization rate, and
      ovarian response. RESULTS: Compared with those in younger women, pregnancy rate,
      pregnancy outcome, fertilization rate, and ovarian response to controlled ovarian
      stimulation were significantly worse in women aged 40 years or older.
      CONCLUSIONS: The outcome of assisted reproduction in women of 40 years of age or
      older was extremely poor. Compared with those in younger women, pregnancy outcome
      and ovarian response to controlled ovarian stimulation were significantly worse
      in women of 40 years or more.

PMID- 9565852
TI  - The evolution of modern technology and its societal impact on biocommunications
      in academe.
AB  - A perspective is presented on how communications technology has evolved over the
      last century and has resulted in the digital revolution and information explosion
      affecting biocommunications today. The paper includes three sections: historical
      perspective, current situation, and future direction. The relationship between
      information technology and societal factors impacting on higher education, health
      care, and the field of biocommunications is discussed and suggestions made for
      understanding and coping with this change.

PMID- 9565850
TI  - The pathogenesis of ovarian hyperstimulation syndrome: a continuing enigma.
AB  - PURPOSE: Our purpose was to review the available literature concerning the
      pathogenesis of ovarian hyperstimulation syndrome and, in light of the most
      recent information, to attempt to provide further insight on this iatrogenic
      complication associated with the induction of ovulation. METHODS: Published
      studies related to this topic were identified through a computerized
      bibliographic search. CONCLUSIONS: The exact mechanism for the development of
      ovarian hyperstimulation syndrome is still obscure. It is well established that
      the syndrome is associated with the process of ovulation induced by either
      luteinizing hormone or human chorionic gonadotropin. Following ovulation, one or
      more substances produced by the ovary are liberated in excess, increasing
      capillary permeability, resulting in the clinical features of the syndrome. It
      may well be that the syndrome is not triggered by a single mechanism but by the
      production and secretion of several substances acting in concert. These may
      include prostaglandins, cytokines, the ovarian reninangiotensin system, vascular
      endothelial growth factor, and nitric oxide.

PMID- 9565854
TI  - The 1997 Margaret Hay Edwards Achievement Medal.

PMID- 9565853
TI  - Resolving discrepancies in image research: the importance of direct observation
      in the illustration of the human soleus muscle.
AB  - A historical analysis of fourteen published illustrations of the soleus muscle
      from the sixteenth to the twentieth century reveals obvious inconsistencies in
      the representational accuracy of the architecture of the muscle. To ensure the
      most accurate illustrations possible, biomedical communicators should conduct
      direct laboratory observations. A review of reference images alone is
      insufficient for assuring anatomical accuracy. Having followed this protocol,
      three architecturally distinct regions of soleus were observed and illustrated
      and the final results suggest that soleus is a complex multipennate muscle with
      significant architectural characteristics not typically represented in published
      illustrations.

PMID- 9565855
TI  - Making a difference.

PMID- 9565856
TI  - Teaching oncology and cancer care to general practice trainees in Sweden: a two
      year prospective, randomized study.
AB  - OBJECTIVE: To improve general practice (GP) trainees' knowledge of and attitudes
      towards oncology and their management of cancer patients. METHOD: A prospective
      study of 33 GP trainees who, after a first assessment, were randomized either to
      attend a two-year cancer course (n = 17) or to a control group (n = 16). Both
      groups were tested at the beginning (pretest) and end (post-test) of the two
      years. The maximum possible score was 76. All tests were corrected blindly by an
      oncologist and a general practitioner. RESULTS: The intervention group showed
      significant post-test-pretest improvements in the domains "knowledge" (mean
      difference 2.6, 95% CI 1.3-3.8) and "attitudes" (mean difference 2.9, 95% CI 0.8
      5.0), but not in "patient management" (mean difference 0.3, 95% CI -0.6-1.2).
      There was no significant change in the test scores of the controls. The total
      mean (post-test-pretest) differences were 8.3 (95% CI 4.9-11.6 for the
      intervention group and -1.4 (95% CI -4.1-1.3) for the controls. CONCLUSION: A low
      intensity two-year cancer course improved the knowledge and attitudes of GP
      trainees. Patient management, however, was not improved and may be more suited
      for hospital training. The current five-year specific training in general
      practice in Sweden seemed to be of limited value in the field of oncology. Thus,
      there is a need for further development of educational tools for cancer training
      of GP trainees, at least in Sweden.

PMID- 9565857
TI  - Improving residents' performances of clinical breast examination.
AB  - BACKGROUND: Clinical breast examination and mammography are recommended as
      combined modalities for breast cancer screening. Rates of mammography are
      increasing; however, clinical breast examination rates are decreasing. Specific
      training in breast examination may be warranted. METHODS: The authors developed
      an ambulatory rotation to teach breast cancer screening to medical residents. To
      assess whether this training improved screening performance, they compared
      clinical breast examination and mammography rates in residents' continuity
      clinics before and after training among residents who were assigned to the
      training program and residents who were not. RESULTS: 314 women patients were
      seen by 28 residents. The rates for annual clinical breast examination and
      mammography were 39% and 71%, respectively. Clinical breast examination rates
      increased by 18% among the residents assigned to the training program, whereas
      they dropped by 13% over than same period among the residents who had not
      received the training (p < 0.005). Female residents performed more clinical
      breast examinations than did their male counterparts (50% vs 34% p < 0.01).
      Mammography rates did not change with training, and were not associated with
      resident gender or career plans. CONCLUSION: Although the residents performed
      mammography at high rates, clinical breast examination rates were low. Short-term
      directed teaching about clinical breast examination increased the performance of
      this screening test, and is important to incorporate into teaching programs.

PMID- 9565858
TI  - Age-related differences in mammography use and in breast cancer knowledge,
      attitudes, and behaviors.
AB  - BACKGROUND: This study examined age differences in breast cancer knowledge,
      attitudes, and early-detection behaviors in a multi-ethnic sample of economically
      disadvantaged women participating in a breast-cancer education outreach program.
      METHODS: Age differences in breast cancer knowledge, perceptions of risk of
      breast cancer, barriers to mammography, recommendations of mammography by health
      professionals, health promotion behaviors, and mammography use and intention were
      investigated. The subjects were 139 women aged 30 or older who were categorized
      in one of three age groups: 30 to 39, 40 to 49, and 50 years old or older.
      RESULTS: One fourth of the women between the ages of 30 and 39 reported both that
      they had had mammography in the past and that they intended to have it in the
      next year. Fifty percent of those in their forties reported mammography use at
      some time in the past, and 56% intended to obtain it in the coming year. Fifty
      percent of those 50 or older reported that they had had mammography in the past
      year. Women aged 40 or older were more likely than those in their thirties to
      report that their healthcare providers had encouraged them to get mammograms. No
      significant age differences were observed in breast cancer knowledge or
      perceptions of personal risk of breast cancer. CONCLUSION: The fact that the
      three age groups were similar in their perceptions of personal risk of breast
      cancer suggests that older women may not be accurately assessing their risk and
      thus may be obtaining screening mammography at less-than-optimal levels.

PMID- 9565859
TI  - A strategy for informing patients and health professionals about unconventional
      cancer therapies.
AB  - BACKGROUND: A Guide to Unconventional Cancer Therapies was produced by the
      Ontario Breast Cancer Information Exchange Project with the intention of meeting
      needs of patients, family members, and health professionals for information about
      unconventional therapies. Concerns raised by health professionals during the
      development of the guide serve as a focus for considering its impact on cancer
      patients who purchased it. MATERIALS AND METHODS: Purchasers of the guide were
      sent a survey questionnaire inquiring about their access to, use of, and
      attitudes toward it. RESULTS: A total of 634 individuals responded to the survey,
      including cancer patients, health professionals, and family members. The guide
      was rated moderately helpful overall, and health professionals found it
      significantly more helpful than did cancer patients. A minority of patients were
      influenced to try an unconventional therapy as a result of reading the guide.
      Those who did try a new therapy typically chose ones that are most popular and
      have few potential negative effects. CONCLUSIONS: As an informational strategy,
      the Guide to Unconventional Cancer Therapies has been successful. Concerns
      expressed by some health professionals about potential harm through implementing
      the strategy have been shown to be largely unwarranted, at least for study
      respondents.

PMID- 9565860
TI  - What do Greek physicians know about managing cancer pain?
AB  - BACKGROUND: Pain is prevalent in cancer patients. Although the World Health
      Organization has issued guidelines for treating pain in cancer patients, pain is
      often not treated optimally. Numerous barriers have been identified that prevent
      health care professionals from providing effective treatment for pain. The
      knowledge and attitudes of health care professionals with regard to pain and its
      impact on the patient are among them. The purpose of the present study was to
      evaluate knowledge about and attitudes toward cancer pain and its management
      among Greek oncologists, surgeons, anesthesiologists, and general practitioners.
      METHOD: Knowledge of the principles and methods of cancer pain treatment was
      assessed by a questionnaire distributed to a representative sample of 1,200 Greek
      physicians. RESULTS: The study results highlight very substantial knowledge
      deficits in the treatment of cancer pain by the evaluated physicians.
      CONCLUSIONS: Cancer pain management in Greece is still developing, and the latest
      knowledge is spreading slowly but steadily.

PMID- 9565861
TI  - Information sources and barriers to cancer treatment by racial/ethnic minority
      status of patients.
AB  - BACKGROUND: This study examined the sources used by cancer patients to obtain
      helpful information regarding their treatment options and side effects and the
      major predictors that facilitated usage of information. METHODS: The survey was
      administered to a representative sample of cancer patients in Texas. The cancer
      treatment facilities from which the patients were sampled were part of the
      University of Texas M. D. Anderson Cancer Center's Texas Community Oncology
      Network. A total of 593 patients (65%) out of 910 contacted responded to the
      survey. RESULTS: The patients reported that providers such as physicians and
      nurses were the most helpful sources of information. White patients tended to use
      books and reference materials more heavily to gather additional information
      regarding their treatment, while black patients relied on pamphlets and
      television. Educational level appeared to have a major influence on the black
      patient's use of printed materials. CONCLUSIONS: The results document the
      important role that providers play in influencing patients' treatment decisions.
      Effective ways to communicate with cancer patients are different for patients
      with different racial backgrounds. Implications for the future development of
      patient education materials and cancer prevention initiatives targeting ethnic
      minorities are addressed.

PMID- 9565862
TI  - Changes in cancer awareness in the Polish population, 1976-1990.
AB  - BACKGROUND: Public awareness of cancer plays a major role in its prevention.
      Knowledge of changes in public awareness provides a good foundation for public
      health education interventions and facilitates their evaluation. METHODS: Three
      nationwide studies of representative samples of the Polish population were
      carried out in 1976, 1986, and 1990. During this period extensive public health
      education was provided. RESULTS: Favorable changes were observed in nearly all
      the aspects investigated. Belief in the curability of cancer increased by 33%;
      knowledge of breast self-examination increased by 46%; the opinion that cancer is
      difficult to detect declined by 19%, knowledge that smoking encourages cancer of
      the lung increased by 15%, and knowledge that cancer is not infectious increased
      by 35%. Other changes were smaller, but were also positive. CONCLUSIONS: Despite
      improvement in the public awareness, there are still urgent unmet needs in health
      education in Poland. For example, efforts should be increased to control smoking
      addiction, especially among the young, persuade women to do breast self
      examination and have Pap tests, and inform the public about healthy lifestyles
      and behaviors that prevent cancer.

PMID- 9565863
TI  - Learning to care for dying patients: a controlled longitudinal study of a death
      education course.
AB  - BACKGROUND: This study examines the long-term impact of a medical-school death
      education course on death-related anxiety and attitudes. METHODS: A four-year
      longitudinal, controlled study design was used. Ninety-nine course participants
      and 92 controls were initially evaluated using the Collett-Lester Fear of Death
      Scale and a semantic differential technique measuring attitudes toward the dying
      patient and his or her family. The evaluation was repeated at the end of the
      course and yearly thereafter. RESULTS: Attitudes towards "treating the dying
      patient" and "dealing with the dying patient's family" were improved as a result
      of the course. The effects were sustained throughout medical school, with
      significant differences between the groups at the end of the course (p < 0.001)
      and for third-year students (p < or = 0.002). Regarding fear of death, analyses
      showed no significant group-time interaction at any test period (p > or = 0.13).
      CONCLUSIONS: Preclinical education has an enduring effect on attitudes involving
      end-of-life care.

PMID- 9565864
TI  - Thoughts from the medical oncologist.

PMID- 9565865
TI  - Marschall Rhone-Poulenc Award Lecture. Nutritional and functional characteristics
      of whey proteins in food products.
AB  - Whey proteins are well known for their high nutritional value and versatile
      functional properties in food products. Estimates of the worldwide production of
      whey indicate that about 700,000 tonnes of true whey proteins are available as
      valuable food ingredients. Nutritional and functional characteristics of whey
      proteins are related to the structure and biological functions of these proteins.
      During recent decades, interest has grown in the nutritional efficacy of whey
      proteins in infant formula and in dietetic and health foods, using either native
      or predigested proteins. This paper focuses attention on the differences and
      similarities in composition of human and bovine milks with reference to infant
      formula. More desirable milk protein composition for consumption by humans is
      obtained by the addition of lactoferrin and more specific fractionations of
      proteins from bovine milk. Optimization of heating processes is important to
      minimize the destruction of milk components during fractionation and preservation
      processes. Some functional characteristics of whey proteins are discussed in
      relation to their properties for application in food products. Information
      obtained from functional characterization tests in model systems is more suitable
      to explain retroactively protein behavior in complex food systems than to predict
      functionality.

PMID- 9565866
TI  - Inhibitory activity against plasmin, trypsin, and elastase in rennet whey and in
      cheese fortified with whey protein.
AB  - The inhibitory activity against trypsin, elastase, and plasmin was determined in
      samples of Danbo 45+ that were manufactured from milk pasteurized at 72, 80, and
      90 degrees C for 15, 30 and 60 s; the corresponding rennet wheys; and Havarti 45+
      manufactured from milk concentrated 1.8-fold, 2.7-fold, and 4.6-fold by
      ultrafiltration. A sensitive colorimetric assay demonstrated that the
      incorporation of thermally denatured whey proteins into the cheese curd by
      pasteurization resulted in a decreased proteinase inhibitory activity against
      trypsin and elastase in Danbo 45+ and against trypsin, elastase, and plasmin in
      the corresponding rennet wheys. However, incorporation of native whey proteins
      into Havarti 45+ by ultrafiltration of the cheese milk resulted in an increased
      inhibitory activity against trypsin and elastase in the cheeses. Cheese
      manufactured from milk concentrated 1.8-fold, 2.7-fold, or 4.6-fold displayed
      trypsin inhibitory activity that was 1.8, 2.9, and 5.1 times, respectively, that
      of the reference cheese. Similarly, the elastase inhibitory activity in the
      cheeses increased 2.2, 3.2 and 7.8 times. The increased inhibitory activity in
      cheese fortified with native whey protein likely contributes to the decreased
      proteolysis and altered ripening characteristics of the resulting cheeses, and
      further, the method can be adapted to detection of other inhibitors if
      sufficiently sensitive substrates are available.

PMID- 9565867
TI  - The addition of oat fiber and natural alternative sweeteners in the manufacture
      of plain yogurt.
AB  - Calorie-reduced yogurts that were fortified with 1.32% oat fiber were prepared
      from lactose-hydrolyzed milk, alone and supplemented with 2 and 4% sucrose or
      with 1.6, 3.6, and 5.5% fructose. Treated samples were compared with unsweetened
      yogurt and with yogurts sweetened with 2, 4, and 6% sucrose. Addition of 5.5%
      fructose increased fermentation time by 60%, slowing down the production of
      lactic, pyruvic, acetic, and propionic acids and the consumption of hippuric and
      orotic acids. Lactose hydrolysis had an inhibitory effect on starter activity at
      the beginning of fermentation and a stimulatory effect at the end of
      fermentation. Fiber addition led to increases in concentrations of acetic and
      propionic acid. Lactobacilli counts were lower in samples treated with fructose.
      The use of hydrolyzed milk had a stimulatory effect on total bacteria and
      lactobacilli counts throughout the cold storage period. After 28 d of storage,
      lactobacilli counts were consistently higher in fiber-fortified yogurts, but
      total bacteria counts were lower. Apparent viscosity increased with the addition
      of sweetener and fiber. Lactose-hydrolyzed and fructose yogurts had the highest
      viscosity values. Samples sweetened with sucrose received the highest scores for
      flavor. Fiber addition decreased overall flavor quality. The lactose-hydrolyzed
      yogurts received the highest flavor scores, independent of fiber fortification.
      Fiber addition improved the body and texture of unsweetened yogurts but lowered
      overall scores for body and texture in yogurts sweetened with sucrose.

PMID- 9565868
TI  - Effects of hydrolysis of milk glycerides on the antimutagenicity of a hexane
      extract of milk.
AB  - Reconstituted nonfat dry milk was treated with different amounts of lipase from
      Pseudomonas fluorescens. Hexane extracts of treated milks were dissolved in
      dimethylsulfoxide and assayed for antimutagenicity using the Ames test
      (Salmonella typhimurium TA 100) against N-methyl, N'-nitro, N-nitrosoguanidine.
      Anti-N-methyl, N'-nitro, N-nitrosoguanidine activity increased significantly as
      the amount of added lipase increased. At the highest lipase concentration tested,
      activity increased 5-fold, suggesting that liberated fatty acids contributed to
      the increased antimutagenicity. The activities of mixtures of pure fatty acids on
      antimutagenesis were examined using the Ames test. At the lowest concentrations
      tested, mixtures of palmitic and stearic acids and mixtures of palmitic and
      isopalmitic acids exhibited greater activity than did the individual acids. At
      all doses tested, mixtures of the monoacylglycerides of palmitic and stearic
      acids exhibited the same activity as the individual components. Quantification of
      fatty acids in milk and yogurt by gas chromatography indicated a 2 to 20-fold
      greater content of free fatty acids in yogurt. The increase in free fatty acids
      may contribute to the increase in antimutagenicity of yogurt relative to that of
      milk.

PMID- 9565869
TI  - Reduction of acyloxyacyl hydrolase activity in circulating neutrophils from cows
      after parturition.
AB  - Bovine neutrophils contain the enzyme acyloxyacyl hydrolase, which hydrolyzes the
      acyloxyacyl linkage of the two nonhydroxylated fatty acyl chains to two 3-hydroxy
      fatty acids in the highly conserved lipid A part of endotoxins with high
      specificity. This hydrolysis decreases the toxicity of lipid A, but the
      immunostimulatory capacity of endotoxins is largely maintained. In two trials, we
      studied the activity of acyloxyacyl hydrolase in neutrophils that had been
      isolated from the blood of 18 dairy cows around parturition. Between 10 and 26 d
      after parturition, the activity of acyloxyacyl hydrolase in neutrophils decreased
      approximately 20% below prepartum activity. At about 2 mo after parturition,
      acyloxyacyl hydrolase activity returned to prepartum values. Changes in
      acyloxyacyl hydrolase activity could not be attributed to changes in binding of
      lipopolysaccharides by the CD14 molecules on neutrophils or monocytes. We
      hypothesize that decreased acyloxyacyl hydrolase activity in neutrophils shortly
      after parturition is a factor that increases the susceptibility of dairy cows to
      coliform mastitis during early lactation.

PMID- 9565870
TI  - Invasion and persistence of Streptococcus dysgalactiae within bovine mammary
      epithelial cells.
AB  - Little is known about bacterial and host factors that contribute to the
      establishment and persistence of intramammary infection by Streptococcus
      dysgalactiae. Streptococcus dysgalactiae adheres to epithelial cells from the
      bovine mammary gland and to extracellular matrix proteins in vitro and invades
      mammary epithelial cell cultures, all of which can be potentially important
      pathogenic mechanisms. In this study, mechanisms involved in the invasion of
      Strep. dysgalactiae into epithelial cells from the bovine mammary gland were
      characterized. Studies were conducted to determine whether Strep. dysgalactiae
      invaded mammary epithelial cell cultures in a dose-dependent manner and whether
      mammary epithelial cells that harbored different numbers of Strep. dysgalactiae
      for varying times were damaged. Bacterial invasion increased as inoculum size
      increased; however, the number of intracellular bacteria was not proportional to
      the inoculum size, increased; however, the number of intracellular bacteria was
      not proportional to the inoculum size, indicating that a finite number of
      organisms is capable of invading epithelial cells. No net increase in
      intracellular organisms was detected at any bacterial density evaluated; however,
      Strep. dysgalactiae remained viable throughout the evaluation. In addition,
      Strep. dysgalactiae did not appear to cause cell injury at any bacterial density
      or time point evaluated. These data suggest that Strep. dysgalactiae can survive
      within mammary epithelial cells for an extended time without losing viability or
      damaging the eukaryotic cell. This feature may be associated with the development
      of persistent infection and protection of organisms from antimicrobial drugs and
      host defense mechanisms and may provide a route for bacterial colonization of
      subepithelial tissues.

PMID- 9565871
TI  - Sources of intramammary infections from Staphylococcus aureus in dairy heifers at
      first parturition.
AB  - The study objective was to identify probable sources and modes of transmission of
      91 Staphylococcus aureus isolates obtained from the colostrum of 76 heifers at
      parturition. Sources cultured were milk (including colostrum), heifer body sites
      (teats, muzzle, rectum, vagina, and lacteal secretions), and environmental sites
      (bedding, insects, housing, water, feedstuffs, humans, nonbovine animals, air,
      and equipment). Staphylococcus aureus isolates were characterized by 63
      phenotypic traits. A similarity coefficient was calculated by herd to identify
      the S. aureus that most closely resembled the S. aureus obtained from heifer
      colostrum. Staphylococcus aureus from a heifer's colostrum was compared with all
      preexisting S. aureus isolates from that heifer's herd. Isolates that were > or =
      90% similar were considered to be identical. Because 30 (of the 91) S. aureus
      isolates from heifer colostrum were collected prior to environmental sampling,
      only 61 S. aureus isolates from heifer colostrum were available for comparison
      among all three sources. Possible sources of S. aureus from heifer colostrum at
      parturition were milk (70%, 43 of 61 isolates), heifer body sites (39%, 24 of
      61), environmental sites (28%, 17 of 61), or no identified source (16%, 10 of
      61). Three heifers with intramammary infection (IMI) from S. aureus at
      parturition had the same S. aureus on their teats prior to parturition. Milk was
      the only source identified for 41% (25 of 61) of isolates from heifer colostrum.
      Isolates from heifer body sites were the only source identified for 5% (3 of 61)
      of heifer colostrum isolates. Staphylococcus aureus from the environment was
      never the sole possible source for S. aureus from heifer colostrum. Data suggest
      that the major sources of S. aureus IMI in heifers at parturition are milk and
      heifer body sites. Contact among heifers may be an important mode of transmission
      of S. aureus leading to IMI in heifers at parturition.

PMID- 9565872
TI  - A simulation of strategies to lower bulk tank somatic cell count below 500,000
      per milliliter.
AB  - In the future, the Pasteurized Milk Ordinance may make milk quality standards
      more stringent by lowering the somatic cell count (SCC) limit on Grade A raw milk
      to 500,000/ml. Therefore, using a discrete event simulation model, we
      investigated the effects of the prevention of intramammary infection (as
      recommended by the National Mastitis Council), lactation therapy, and dry cow
      therapy (all seven possible combinations) on bulk tank SCC; milk, fat, and
      protein yields; prevalence of intramammary infection; and culling for mastitis.
      Untreated controls were also tested. Ten replicates of each intervention and each
      control were run for 2 simulated yr, including the daily sampling of 100 cows.
      The goal was to lower bulk tank SCC < 500,000/ml in the 2nd yr for herds that
      previously had stable bulk tank SCC between 500,000 and 750,000/ml. Although all
      strategies occasionally met this goal, on no occasion did all replicates perform
      without a violation in the 2nd yr of the study (median last month of violation
      ranged from mo 12 to 23). The combination of the prevention of intramammary
      infection, lactation therapy, and dry cow therapy resulted in the lowest bulk
      tank linear score, most replicated without a violation in the 2nd yr, fewest
      months with a bulk tank linear score > or = 5.3, and fewest mastitis culls. The
      combination of the prevention of intramammary infection and dry cow therapy also
      was favorably ranked (highest milk yield, fewest clinical intramammary infections
      during lactation, and highest percentage of uninfected cows).

PMID- 9565873
TI  - Design and validation of a dynamic discrete event stochastic simulation model of
      mastitis control in dairy herds.
AB  - A dynamic stochastic simulation model for discrete events, SIMMAST, was developed
      to simulate the effect of mastitis on the composition of the bulk tank milk of
      dairy herds. Intramammary infections caused by Streptococcus agalactiae,
      Streptococcus spp. other than Strep. agalactiae, Staphylococcus aureus, and
      coagulase-negative staphylococci were modeled as were the milk, fat, and protein
      test day solutions for individual cows, which accounted for the fixed effects of
      days in milk, age at calving, season of calving, somatic cell count (SCC), and
      random effects of test day, cow yield differences from herdmates, and
      autocorrelated errors. Probabilities for the transitions among various states of
      udder health (uninfected or subclinically or clinically infected) were calculated
      to account for exposure, heifer infection, spontaneous recovery, lactation cure,
      infection or cure during the dry period, month of lactation, parity, within-herd
      yields, and the number of quarters with clinical intramammary infection in the
      previous and current lactations. The stochastic simulation model was constructed
      using estimates from the literature and also using data from 164 herds enrolled
      with Quality Milk Promotion Services that each had bulk tank SCC between 500,000
      and 750,000/ml. Model parameters and outputs were validated against a separate
      data file of 69 herds from the Northeast Dairy Herd Improvement Association, each
      with a bulk tank SCC that was > or = 500,000/ml. Sensitivity analysis was
      performed on all input parameters for control herds. Using the validated
      stochastic simulation model, the control herds had a stable time average bulk
      tank SCC between 500,000 and 750,000/ml.

PMID- 9565874
TI  - Vegetational association of host-seeking adult blacklegged ticks, Ixodes
      scapularis Say (Acari: Ixodidae), on dairy farms in northwestern Wisconsin.
AB  - As a measure of the risk for exposure to Lyme disease, we estimated the
      distribution of host-seeking adults of the blacklegged tick, Ixodes scapularis
      Say, on dairy farms in Barron County in northwestern Wisconsin. Vegetation
      ecotypes that were common to 18 farms that were representative of the county were
      surveyed by flag sampling. Tick prevalence and abundance, which were similar
      during fall and spring periods, were very low in farmhouse yards and forage
      croplands; only a single male was collected from 17 lawns. Sampling of 18
      pastures with lactating cows also yielded only a single I. scapularis. In
      contrast, I. scapularis adults were captured in 9 of 37 samples from 18 pastures
      with heifers and dry cows; in those pastures, ticks were associated with woods
      and secondary vegetation or margins of pastures adjacent to woodlands.
      Blacklegged ticks were most prevalent and numerous in ungrazed woodlands; adults
      were captured in 27 of 53 samples on 13 of 15 farms, particularly when evidence
      of white-tailed deer, Odocoileus virginianus (Zimmermann), was apparent. The risk
      of encountering adult blacklegged ticks on dairy farms in Barron County,
      Wisconsin is therefore greatest in woodlands habitat. The presence of adult ticks
      in pastures with heifers and dry cows establishes an ecological basis for the
      exposure of dairy cattle to adult I. scapularis. Pastures with lactating cows,
      farmhouse yards, and forage croplands represent negligible risk.

PMID- 9565875
TI  - Effects of electric and magnetic fields on nocturnal melatonin concentrations in
      dairy cows.
AB  - Sixteen multiparous, pregnant, lactating Holstein cows (weighing 600 +/- 50 kg,
      at 184.8 +/- 52 d of lactation, and at 101.9 +/- 43 d of gestation) were confined
      to wooden metabolism cages and exposed to a vertical electric field of 10 kV/m
      and a uniform horizontal magnetic field of 30 microT. The trial was conducted
      using a switchback statistical design. Cows were divided into two sequence groups
      of 8 cows each. One sequence group was exposed for three periods of 28 d each.
      The electric and magnetic fields were off during the first period, on during the
      second period, and off during the final period. The second sequence group was
      exposed for three periods also, but the activity of the fields was reversed (on
      during the first period, off during the second period, and on during the third
      period). On d 25 of each exposure period, blood samples were obtained every 0.5 h
      for 14 h starting at 1700 h to determine melatonin concentration. Nocturnal
      melatonin concentrations did not show any variation that could be attributed to
      exposure to electric and magnetic fields.

PMID- 9565876
TI  - Effect of long-chain fatty acids on triglyceride accumulation, gluconeogenesis,
      and ureagenesis in bovine hepatocytes.
AB  - A relationship between increased lipid concentration in the liver and reduced
      hepatic function has been suggested; however, there is little direct evidence of
      change in specific hepatic functions. Hepatocytes were obtained from ruminating
      calves and were incubated as monolayers for 36 h. The media contained a mixture
      of nonesterified fatty acids (NEFA) at 0, 0.5, 1.0, and 1.5 mM NEFA with molar
      proportions of 0.435 oleate, 0.319 palmitate, 0.144 stearate, 0.049 linoleate,
      and 0.053 palmitoleate. Ureagenesis or gluconeogenesis was measured from 48 to 51
      h after plating using hepatocytes that had only previous (12 to 48 h), only
      concurrent (48 to 51 h), or previous and concurrent (12 to 51 h) exposure to
      NEFA. A previous 36-h exposure to NEFA caused cell triglyceride accumulation,
      yielding triglyceride concentrations that corresponded with liver that is
      clinically described as normal to moderately fatty. Previous, prolonged exposure
      to NEFA reduced ureagenesis and increased gluconeogenesis. Concurrent exposure to
      NEFA did not significantly affect gluconeogenesis or ureagenesis and did not
      alter the residual effect of prolonged incubation with NEFA. Reduced ureagenesis
      was related to increased cell triglyceride accumulation independently of other
      direct NEFA effects. Decreased ureagenic capacity may play a role in the
      morbidity associated with periparturient fatty liver in dairy cows.

PMID- 9565877
TI  - Relationship of triglyceride accumulation to insulin clearance and hormonal
      responsiveness in bovine hepatocytes.
AB  - The accumulation of triglycerides in the liver has been associated with reduced
      hepatic function; however, direct evidence that fat accumulation causes decreased
      liver function is lacking. Hepatocyte monolayers isolated from ruminating calves
      with an initial low triglyceride concentration were either loaded or not loaded
      with triglycerides by incubation with 1.5 or 0 mM exogenous nonesterified fatty
      acids from 12 to 48 h after plating. Basal rates of synthesis of albumin and
      protein were not affected by triglycerides in the cell. Inclusion of insulin and
      glucagon from 12 to 72 h after plating increased rates of albumin and protein
      synthesis. Hepatocytes loaded with triglycerides were less sensitive to the
      hormonal stimulation of albumin and protein synthesis than were normal
      hepatocytes. Insulin clearance rates were also lower in hepatocytes loaded with
      triglycerides than in normal hepatocytes. Decreased insulin clearance and
      hormonal control of protein synthesis could contribute to the etiology of
      metabolic disorders that are associated with periparturient fatty liver in dairy
      cows.

PMID- 9565878
TI  - Peptides generated from milk proteins in the bovine mammary gland during
      involution.
AB  - Proteolytic activity in mammary gland secretions is associated with hydrolysis of
      secretory proteins during involution. Peptides generated from hydrolysis of milk
      proteins were characterized in secretions from the bovine mammary gland during
      involution to understand the fate of the milk proteins better. Mass spectral
      analysis of mammary secretions showed numerous peptides ranging between 0.7 and
      14 kDa during mammary involution, but these peptides were not observed in normal
      milk. Mass spectral profiles representing discrete peptide fragments were similar
      on d 7, 14, and 21 of involution, suggesting that milk proteins were only
      partially hydrolyzed during involution. N-Terminal amino acid sequences of four
      peptides indicated that they were produced by hydrolysis of beta-casein during
      involution and probably resulted from plasmin hydrolysis. A 20-kDa peptide was
      identified as a fragment of a 39-kDa protein that was previously identified in
      bovine mammary secretions during involution. Mass spectral analysis of
      lactoferrin isolated from mammary secretions during involution showed major
      hydrolytic products. Immunoblot analysis confirmed that lactoferrin that was
      isolated from mammary secretions during involution contained a number of
      hydrolytic products. Intramammary hydrolysis of milk proteins by plasmin probably
      leads to the generation of the discrete peptides observed in the mammary
      secretions and contributes to the fate of these proteins during involution of the
      bovine mammary gland.

PMID- 9565879
TI  - Milk production of Holstein heifers fed either alfalfa or corn silage diets at
      two rates of daily gain.
AB  - Seventy-five prepubertal heifers were fed diets based on either alfalfa silage or
      corn silage plus soybean meal for daily gains of either 725 or 950 g/d in a 2 x 2
      factorial. Heifers were fed from 175 to 325 kg of body weight (BW). The alfalfa
      diet contained more digestible protein and less digestible energy than did the
      diet containing corn silage plus soybean meal. Actual gains were preexperimental
      BW gain, 633 g/d; lowest experimental BW gain, 785 g/d; highest experimental BW
      gain, 994 g/d; lowest postexperimental BW gain, 494 g/d; and highest
      postexperimental BW gain, 546 g/d. Compensatory postexperimental BW gains of
      heifers fed a common diet allowed the heifers to calve at 732 d of age. The
      postcalving BW was 508 kg, and precalving height at withers was 134 cm. A total
      mixed diet containing 17.1% CP and digestible energy at 3.12 Mcal/kg of dry
      matter was fed during lactation. Feed intake, milk and milk component production,
      and milk composition were not affected by either experimental diet or growth
      rate. As covariates, milk production was related to age at calving and was more
      strongly related to BW after calving, but no differences were observed among
      growth diets. Differences in protein and energy concentrations in experimental
      growth diets did not affect lactation performance. About 75% of total BW gains
      during the treatment period occurred before puberty, but rate of gain did not
      affect milk production. This lack of an effect of prepubertal growth rates on the
      milk production of primiparous heifers is consistent with six other similar
      studies that were conducted recently.

PMID- 9565880
TI  - Protein preservation and ruminal degradation of ensiled forage treated with heat,
      formic acid, ammonia, or microbial inoculant.
AB  - The objectives of this study were to determine whether treatment of forage with
      heat would reduce proteolysis during subsequent fermentation. In Experiment 1,
      direct-cut barley forage and alfalfa were untreated, microwaved, or steamed and
      then ensiled in laboratory silos as wilted forages. Silages of microwaved or
      steamed forage showed a marked increase in N bound to neutral detergent fiber and
      in the recovery of protein; however, alfalfa silages also had high pH values and
      concentrations of butyric acid. In Experiment 2, steam heating was compared with
      formic acid and NH3 treatments for the prevention of proteolysis in alfalfa
      silages. Silage of steamed alfalfa had a greater amount of N bound to neutral
      detergent fiber and greater recovery of protein than did control silage or
      silages of forage treated with formic acid or NH3. Silage of steamed forage had
      lower pH values than did silages of wilted, direct-cut, or control forage.
      Microbial innoculant added to steamed forage increased the recovery of protein.
      Silage of steamed forage had less aerobic stability than did silage of direct-cut
      forage. Ruminal degradability of crude protein (CP) and organic matter of silage
      from both experiments was evaluated. Degradability of CP was 8 to 26 percentage
      units lower in silages of microwaved or steamed forage in Experiment 1 than in
      silage of unheated forage because of slower degradation rates, but all had
      similar undegraded CP after incubation for 72 h. In Experiment 2, wilting, steam,
      formic acid, and NH3 treatments affected CP degradability similarly, but CP
      degradability was decreased when compared with silage of direct-cut forage
      without treatment.

PMID- 9565881
TI  - Effects of ground, steam-flaked, and steam-rolled corn grains on performance of
      lactating cows.
AB  - Five types of processed corn were compared to determine the effects of processing
      on lactational performance and nutrient digestibilities in dairy cows. Forty
      lactating Holstein cows averaging 160 +/- 60 d in milk were randomly divided into
      five groups on the basis of pretreatment milk yields and were fed diets
      containing 40% corn grain for 56 d. Treatments were 1) finely ground corn, 2)
      coarsely ground corn, 3) steam-flaked corn at a low density, 4) steam-flaked corn
      at a medium density, and 5) steam-rolled corn. Cows fed the diet containing steam
      flaked corn at a medium density had a higher milk yield (37.1 kg/d) than did cows
      fed the diets containing coarsely ground corn, steam-flaked corn at a low
      density, or steam-rolled corn; cows fed the diet containing finely ground corn
      had an intermediate milk yield (35.5 kg/d). Efficiency of feed utilization was
      greater, and dry matter intake was lower, for cows fed the diet containing finely
      ground corn than for cows fed the other diets. The fat content of milk was higher
      for cows fed the diets containing coarsely ground corn and steam-rolled corn than
      for cows fed the diet containing steam-flaked corn at a medium density. Milk
      protein and SNF contents and yields of protein, lactose, and SNF did not differ
      among diets. Apparent starch digestibilities in the total digestive tract were
      lower for diets containing coarsely ground corn (87.4%) and steam-rolled corn
      (91.3%) than for the other diets (X = 96.3%). Milk yield was highest for cows fed
      the diet containing steam-flaked corn with a medium density. Fine grinding
      resulted in the greatest efficiency of feed utilization.

PMID- 9565882
TI  - Effects of rumen-undegradable protein and feed intake on nitrogen balance and
      milk protein production in dairy cows.
AB  - An experiment was designed to determine the response of milk protein production
      and N utilization in dairy cows to supplementation of a predominantly rumen
      undegradable protein (RUP) mixture with a fixed amino acid (AA) pattern and the
      response to the amount of feed intake. The experiment was designed as a 6 x 6
      Latin square with a 3 x 2 factorial arrangement of treatments. The factors were
      three concentrations of RUP supplement (4.5, 14.9, and 29.1% of dry matter
      intake) and two levels of feed intake restriction (10 and 20%) of the basal diet.
      The supplement was designed to approximate a postruminal AA pattern that was
      similar to bovine caseins for Met, Lys, Phe, His, and Thr. Measurements were made
      during the last 5 d of each 21-d period. Milk protein production responded
      linearly as the concentration of RUP supplement in the treatment diet increased
      within the given range. The difference in feed intake restriction did not affect
      milk protein production. Efficiency of N utilization for milk production exceeded
      30% for cows fed the lowest RUP supplement. Results indicated that there is an
      opportunity to increase milk protein production by using RUP formulations that
      are balanced for AA while minimizing waste N excretion.

PMID- 9565883
TI  - Fatty acid composition of milk from Holstein cows fed oleamide or canola oil.
AB  - Based on previous in vitro results that showed reduced biohydrogenation of
      oleamide by ruminal microbes, this study was conducted to determine whether the
      addition of oleamide to the diets of dairy cows would enhance the C18:1
      concentration in milk. Nine first lactation Holstein cows were fed three diets in
      a 3 x 3 Latin square replicated three times. Each period lasted 3 wk. The total
      mixed diets consisted of 42% corn silage and 58% concentrate (dry matter basis)
      with either no added fat (control), 3.5% high oleic canola oil, or 3.5% oleamide.
      Dry matter intake was reduced when oleamide was added to the diet but not when
      canola oil was added. Milk yields were the same for cows fed all three diets.
      Canola oil reduced fat-corrected milk yield and milk fat concentration, but these
      were not affected by oleamide. Milk protein concentration was lower for cows fed
      oleamide than for cows fed canola oil. Milk C18:1 averaged 23.16% of total fatty
      acids for cows fed the control diet and increased to 35.13% when canola oil was
      fed. Oleamide further increased C18:1 to 48.16% of total fatty acids in milk. All
      fatty acids with > or = 16 carbon chain length were reduced by oleamide. Oleamide
      was more effective than was canola oil in this study at increasing the oleic acid
      content of bovine milk. Oleamide reduced dietary intake when added at 3.5% of the
      dietary dry matter but still had no effect on milk yield or milk composition.

PMID- 9565884
TI  - Nutrition management, nitrogen efficiency, and income over feed cost on dairy
      farms in Costa Rica.
AB  - Twenty-two dairy farms in two ecologically different zones were visited
      repeatedly during the dry and wet seasons of 1995 to evaluate nutrition and
      pasture management, N efficiency on the farm, and income over feed costs with the
      use of a management support program. Excessive amounts of concentrates were fed,
      and no differences in amounts were detected between seasons. Utilization of
      forage was consequently low and even negligible on some farms. The amount of
      crude protein in the diet was generally too high. The removal of N from the farms
      via milk and culling represented 27 and 31% of the total N input for the two
      regions, respectively. The income over feed costs per cow ($3.04 and $1.84/d,
      respectively) was considered reasonable despite the high amount of concentrates.

PMID- 9565885
TI  - Optimization of sire selection based on maximization of guaranteed income and
      risk associated with sire merit.
AB  - A method based on discounted income and risk assessment was developed to aid in
      the selection of dairy sires. The discounted profit generated from milk
      production of daughters was proposed as the suitable composite selection
      criterion to combine estimates of predicted transmitting ability (PTA) for yields
      of milk, fat, and protein and estimates of sire evaluations for dystocia or
      expected progeny difference. Steps are described to derive discounted profit
      (defined as expected income) for a sire with known PTA and evaluation for
      dystocia. The derivation of profit considered costs for semen, dystocia, heifer
      raising, production and maintenance of the daughter, and income from milk.
      Variance of income from a sire depended on the reliability of his PTA and
      evaluation for dystocia. Total variance from a selected set of sires was defined
      as the risk. A quadratic programming procedure was developed to identify the best
      set of sires from a given pool of sires that met a desired expected income goal
      with minimum risk. Combinations of sires with minimum risk for all possible
      levels of expected income were defined by the expected income variance frontier.
      The set of sires at the maximum lower boundary for 95% confidence of the expected
      income variance frontier was defined as the optimum set of sires to be selected;
      the optimum set maximized the 95% guaranteed expected income. The quadratic
      programming procedure provided the optimum percentage of cows to be mated to each
      sire in the selected set.

PMID- 9565886
TI  - Evaluation of adenosine triphosphate-bioluminescence hygiene monitoring for
      trouble-shooting fluid milk shelf-life problems.
AB  - An ATP-bioluminescence hygiene monitoring system was used to evaluate food
      contact surfaces in four fluid milk plants experiencing shelf-life problems.
      Postpasteurization surfaces, including gaskets, pipe fittings, valves, filler
      parts, and hand-washed items, were evaluated. Swab results, measured in relative
      light units proportional to total recovered ATP, were compared with results from
      the standard method of microbiological swab contact for adjacent sites of equal
      area. Microbiological procedures included standard plate count, coliform count,
      and Gram-negative bacteria count. Standard plate counts were < 1, 1 to 50, and >
      50 cfu in 65, 22, and 13% of swabbed sites of < 100 RLU (relative light units);
      in 9, 36, and 55% of sites of 100 to 150 RLU; and in 22, 18, and 60% of sites of
      > 50 RLU, respectively. Thirteen sites were found with standard plate counts >
      10,000 cfu per site and identified with the hygiene monitoring system (> 150
      RLU). Gram-negative bacteria were the dominant bacterial type in a majority of
      these samples. Gram-negative bacteria were detected in a total of 22 sites
      tested; mean counts were 2100 cfu per site for Gram-negative bacteria and 20 cfu
      per site for coliform bacteria. Although limited to use on accessible sites, the
      hygiene monitoring system proved to be an effective, rapid tool for identifying
      the possible sources of postpasteurization contamination in the fluid milk plants
      evaluated.

PMID- 9565887
TI  - Profitability of moderate intensive grazing of diary cows in the northeast.
AB  - Empirical analysis of the profitability of moderate grazing are presented based
      on sample dairy farms in Pennsylvania and New York. Net income per cow was higher
      for dairy farms that employed moderate intensive grazing than for dairy farms
      that employed extensive grazing. Income appeared to be adequate for family living
      expenses, but moderate intensive grazing could not be considered a high profit
      system. Detailed analyses of dairy farms that employed moderate and extensive
      grazing in northern Pennsylvania indicated that returns to management and owner
      equity were higher for pasture enterprises than for corn silage or hay
      enterprises. Positive dairy profits were related to lower feed costs. Milk
      production was lower on farms that employed moderate grazing than on farms that
      employed extensive grazing. Logit regression analysis characterized farms that
      employed moderate intensive grazing as oriented toward dairy rather than toward
      crop production; these farms had lower culling rates and a greater dependence on
      milk sales as a share of total sales. The reduced use of fertilizers and
      chemicals suggests that moderate grazing had environmentally sustainable
      features.

PMID- 9565888
TI  - Estimating the available energy content of feeds for dairy cattle.
AB  - The available energy content of feeds must be known before diets can be
      formulated, but the difficulty in measuring energy availability requires that
      estimated values be used. Based on production data, the current system using net
      energy for lactation (NEL) or total digestible nutrients (TDN) over-valued the
      energy in feeds by 7 to 8%. A standard discount of 8 TDN units was used for both
      NEL and TDN. When the discount was calculated from actual intake (4 units per
      increment of maintenance), feed values for NEL and TDN were overestimated by 5 to
      6%. Most feed values for NEL and TDN are estimated from acid detergent fiber.
      These models do not account for all sources of variation in digestibility, do not
      allow for variable discounts based on intake and associative effects, and are
      specific for a given population. Mechanistic models account for many sources of
      variation and can be modified to include variable discounts based on digestion
      and passage kinetics. The equation used to convert TDN to NEL does not consider
      the source of the digestible energy. The NEL of the fat that is contained within
      feeds is under-valued, and fiber is probably overvalued. Single-component
      equations are not adequate to describe the complex processes that determine
      energy availability. The current NEL and TDN systems overvalue the energy in
      feeds, but both systems still work remarkably well. These systems need to be
      modified to improve accuracy, but they should not be discarded.

PMID- 9565889
TI  - Diet energy requirements of growing Holsteins.
AB  - The conceptual bases of recent NRC publications of nutrient requirements to meet
      dietary energy needs of growing Holsteins, emphasizing heifers gaining 0.75 kg/d,
      are described and compared with several world systems and with body composition
      data. Requirements of Holsteins for net energy for maintenance are generally
      thought to be higher (from 7 to 20%) than those of British beef breeds. Total
      estimates of metabolizable energy requirements are quite similar for most energy
      systems for cattle at 200 to 400 kg of body weight. For heavier cattle, the
      energy density estimates based on beef breed equations project higher
      metabolizable energy for gain and total metabolizable energy requirements.
      Extrapolations from the chemical composition of growing Holstein heifers indicate
      that, at the slower growth that is typical of replacements, energy densities are
      lower than for more rapidly growing heifers and that net energy requirements are
      consistent with current US standards.

PMID- 9565890
TI  - Comparison of the National Research Council energy system for lactating cows with
      four European systems.
AB  - The structure, prediction steps, and accuracy of the US (NRC), United Kingdom
      (ARC), Dutch (VEM), French (UFL), and German (NEL) systems for feeding high
      producing cows were compared. Simulations were made using 15 feeds ranging from
      hays to cereals. Agreement was satisfactory among European systems for the
      prediction of metabolizable energy and net energy for lactation (NEL) contents of
      feeds and the quantities of feeds in balanced diets necessary to meet the energy
      requirements of lactating cows. The metabolizable energy and NEL contents of
      feeds seemed overestimated by the US system compared with results using the
      European systems, and the ratio of NEL to total digestible nutrients was almost
      constant, unlike the other systems. Estimating the NEL content of feeds for a
      level three times maintenance intake allowed satisfactory rationing for the
      production of 20 to 25 kg of fat-corrected milk/d. However, feed allowances
      seemed underestimated for higher milk production, especially with diets based on
      hay, probably because of the overestimation of feed NEL content, the
      underestimation of level of feeding, and the effects associated with feeding
      levels > 3 and high concentrate diets.

PMID- 9565891
TI  - Influence of supplemental fats on reproductive tissues and performance of
      lactating cows.
AB  - Fat supplementation (about 3% of dietary dry matter) has often positively
      influenced the reproductive status of the dairy cow, including increased size of
      the ovulatory follicle, increased numbers of ovarian follicles, increased plasma
      concentration of progesterone, reduced secretion of prostaglandin metabolite,
      increased lifespan of the corpus luteum, and improved fertility. Supplemental fat
      may allay partially negative energy status during the early postpartum period,
      yet often the positive reproductive influence of supplemental fat has been
      independent of the energy status of the cow. The fatty acid profile of
      supplemental fats is influential to their impact. Linoleic acid and
      eicosapentaenoic acid (found in fish meal) are proven inhibitors of
      cyclooxygenase in endometrial tissue of dairy cows. As a result, endometrial
      secretion of PGF alpha can be suppressed, thus potentially preventing early
      embryonic death. This process may be aided by the effect fat has in suppressing
      estradiol-17 beta secretion, thus reducing uterine PGF2 alpha secretion and
      decreasing the sensitivity of the corpus luteum to PGF2 alpha. Targeting of
      dietary fatty acids toward ovarian and uterine function may enhance efficiency of
      reproductive management and fertility.

PMID- 9565892
TI  - A veterinary perspective of on-farm evaluation of nutrition and reproduction.
AB  - Reproductive herd health programs of the 1960s and 1970s focused primarily on the
      control of infectious and noninfectious diseases of the reproductive tract,
      estrus detection, breeding technique, semen quality and handling, and endocrine
      imbalances. Despite veterinary intervention, conception rates dropped from 55%
      before this period to 45% after this period, but milk production increased
      greatly. Because studies have shown that the additional nutritional needs for
      high producing cows may be a factor limiting reproduction, bovine practitioners
      have become more involved with dairy nutrition. New emphasis has been placed on
      the concept of total production medicine with the anticipation that improved
      nutrition would improve reproduction. Because of a better understanding of the
      dynamics of energy in the dairy cow and its effect on reproduction, fertility
      examinations now include nutrition monitoring and body condition scoring. Several
      relationships between nutrition and fertility have been identified: high
      producing thin cows that drop 0.75 to 1.0 in body condition score resulting in
      anestrus; fat dry cows that develop fatty livers and associated postpartum
      disease; heifers that have good milk production but prolonged anestrus; dry cows
      with ration imbalances during the transition period that develop milk fever,
      retained placenta, displaced abomasum, metritis, or endometritis; lactating cows
      with disease in midlactation, especially feet and leg problems, resulting in
      lowered fertility; and healthy, lactating cows with poor conception that have
      high concentrations of urea N in blood or milk.

PMID- 9565893
TI  - Economists, public provision, and the market: changing values in policy debate.
AB  - Among health services researchers, an "economizing model" of health care has
      eclipsed two traditional models, "social conflict" and "collective welfare." The
      older models emphasized social solidarity and distributive justice, but the newer
      one focuses on improving efficiency, minimizing risks borne by third-party
      payers, constraining cost increases, and improving the functioning of markets.
      This article examines one source of the economizing model, the work of several
      early and persistently prominent economists of health care, especially Mark
      Pauly, Martin Feldstein, and Joseph Newhouse and his colleagues at the Rand
      Corporation. In particular, it explores their role in transforming perceptions of
      health care from a set of special services into an ordinary commodity, in giving
      currency to apparently dispassionate as opposed to overtly value-laden analysis,
      and in according priority, among health services researchers and policy makers,
      to economists' traditional interest in fostering smoothly functioning markets. It
      exhibits their principal policy recommendation-income-graduate cost sharing-the
      sources and character of their modes of analysis, and the character of their
      influence on policy makers. The article concludes that the supposedly value-free
      economic analysis of health care rests on a cluster of values that inhibit the
      expression of social solidarity and the formulation of policies intended to
      foster distributive justice.

PMID- 9565894
TI  - A cross-national comparison of orphan drug policies: implications for the U.S.
      Orphan Drug Act.
AB  - Six countries--Canada, France, Japan, Sweden, the United Kingdom, and the United
      States--were studied to compare public policies affecting the development and
      marketing of pharmaceuticals for rare diseases (i.e., orphan drugs). Information
      was obtained from a variety of published and unpublished sources, including
      interviews with public policy and pharmaceutical experts in each country. This
      article presents different approaches to encouraging the development of orphan
      drugs while ensuring access by regulating their prices. Additionally, the article
      describes access to orphan drugs as promoted by special coverage for population
      subgroups, disease categories, and/or specific drugs. Not all efforts to increase
      access to orphan pharmaceuticals have been the result of government action, as
      illustrated by the proliferation of for-profit organizations that specialize in
      orphan drugs. The many policy options from other countries identified in this
      study are especially relevant, given increasing calls for reform of the U.S.
      Orphan Drug Act.

PMID- 9565895
TI  - Back to the future: community involvement in the Healthy Start Program.
AB  - This article discusses how community involvement is incorporated into Healthy
      Start, a major initiative to reduce infant mortality in selected communities with
      disproportionately high levels of infant mortality. Based on site visits to each
      of the fifteen original Healthy Start project areas, we discovered that two main
      community involvement strategies were used: a service consortium model and a
      community empowerment model. In the service consortium model, the community is
      involved primarily through a consortium of local providers, other professionals,
      and some governmental representatives who help to plan services. The community
      empowerment model involves the community by engaging neighborhood-based groups,
      contracting with community-based organizations, employing community residents as
      lay workers in the Healthy Start program, and creating other economic development
      initiatives. Important lessons drawn from this study are that the purpose and
      commitment to community involvement is not always clear; that it is difficult to
      involve community residents; that efforts to involve the community are extremely
      labor intensive; that given monetary incentives, it is easier to involve
      community providers than residents; that community involvement may conflict with
      efficient program operations; that increased community involvement may create
      program goals that differ from the program's original goals; and that community
      involvement may slow program development.

PMID- 9565896
TI  - The states and health care reform: the road traveled and lessons learned from
      seven that took the lead.
AB  - During the past decade, an area of major policy activity among the states has
      been that of health care reform. As of May 1993, seven states--Florida, Hawaii,
      Massachusetts, Minnesota, Oregon, Vermont, and Washington--had progressed the
      furthest in enacting comprehensive statutes designed to expand health insurance
      coverage and slow the growth of health care costs. This article reviews the
      activities of these states to achieve health care reform and the lessons learned
      from those activities. The analysis focuses specifically on identifying the
      common problems addressed and determining the common factors that maximized
      states' opportunities for success. In all, some nine lessons are identified that
      have relevance for other states wishing to follow a similar road to reform. Most
      important among these are a "window of opportunity" for policy action, having
      entrepreneurial leadership to push the reform agenda forward, and support from
      key stakeholder interests. If these conditions of opportunity, policy
      entrepreneurship, and stakeholder commitment are met, a state can move forward in
      addressing key aspects of its health care reform agenda.

PMID- 9565897
TI  - Variation in state spending for long-term care: factors associated with more
      balanced systems.
AB  - Pressures to turn over responsibility for long-term care to the states will
      exacerbate the already sizable difference in such efforts. This article describes
      the nature of the interstate variation in the types and amounts of long-term care
      provided under Medicaid. The average Medicaid long-term care expenditure on
      persons sixty-five years and older varies from $2,720 in New York to $380 in
      Arizona. Likewise, payments for home and community-based services (HCBS) vary
      from $1,180 in New York to $29 in Mississippi. Only a modest portion (28 percent)
      of the variance in total long-term care expenditures appears to be related to
      differences in population characteristics, and even less (7 percent) appears to
      be related to differences in HCBS expenditures. When supply factors (e.g.,
      nursing home beds) are added, the explained variance increases to 52 percent and
      17 percent, respectively. Medicare replaces some--but not most--of the difference
      in Medicaid home and community-based services payments.

PMID- 9565898
TI  - Developmental theory and the postmodern psychoanalyst.

PMID- 9565899
TI  - Experience as a guide to psychoanalytic theory and practice.

PMID- 9565900
TI  - Coordinating developmental and psychoanalytic processes: conceptualizing
      technique.
AB  - Throughout childhood and adolescence, psychological growth proceeds in a sequence
      of progressive hierarchical organizations. Consequently, children are
      continuously consolidating existing positions or are in transition from one to
      another. When analytic treatment is proposed, analysts often find themselves in
      the position of being required to technically coordinate the requirements of the
      analytic process with those of the ongoing developmental process. While it is the
      patient who will ultimately bring the needs of both processes together, the
      approach the analyst assumes to recognizing and addressing these needs can have a
      facilitating influence on the treatment. Play, for example, is a window on old
      conflicts and impaired object relationships from the past, but it is also a way
      in which children consolidate existing organizational hierarchies. Similarly, the
      analytic interaction provides a pathway to the past, but it is also used by
      children to provide the building blocks for newly emerging structures. To
      facilitate further clinical research, a conceptual outline of the relationship
      between the two processes is provided.

PMID- 9565901
TI  - Refusal of autonomy: the use of words by a young adult in analysis.
AB  - Analytic work with a depressed twenty-three-year-old woman is presented showing
      how she used ruminative thoughts to maintain a fixed internal dyadic relationship
      in which neither self not object had autonomy. The resulting omnipotent/impotent
      impasse meant that she was unable to move forward in her development. In the
      analysis this relationship was externalized through her use of words, which were
      employed as actions designed to have a concrete effect on both her self and her
      analyst. For a long period in the analysis it was essential to understand and
      interpret the function of her words, rather than to look for symbolic meaning,
      and it was this which gradually enabled her to take a third, observing, position
      from which she had greater freedom to operate as a adult.

PMID- 9565902
TI  - An expanded developmental line for negation: rejection, refusal, denial.
AB  - Freud's 1925 paper on negation provides the foundation for exploring an expanded
      developmental line of negation. Incorporating evidence from child language
      studies and explanations from the philosophy of language, this paper describes
      three types of negation that emerge in a developmental sequence: rejection,
      refusal, and denial. Clinical examples illustrate each type of negation,
      demonstrating how it might appear in clinical interactions. Along the way,
      confusions in terminology (due partly to translation problems) and questions for
      developmental theory are discussed. An expanded developmental line of negation
      provides additional interpretive perspectives on the forms of defense that Freud
      was addressing in "Negation" (1925) and subsequent papers (1927, 1940a,b).

PMID- 9565903
TI  - Screen reconstructions: traumatic memory, conviction, and the problem of
      verification.
AB  - Just as formerly recalled screen memories may be remembered again in the course
      of psychoanalysis, so new screen phenomena can arise during the treatment
      process. This paper attempts to relate the process of reconstruction and the
      occurrence of a type of screening. It is proposed that, under certain
      circumstances, psychoanalysis can result in a mutually determined screen
      construction that both patient and analyst consider convincing and valid but
      which may, for the most part, actually be untrue as a result of the screen
      function. Screen memories arising during the reconstructive process resemble the
      deja vu and deja raconte situation in that the experience is felt with certainty
      to have actually occurred previously, although a degree of doubt about its having
      happened can consciously or unconsciously coincide. Factors contributing to the
      formation of screen constructions include regressive aspects of the analytic
      situation; superego elements and the experience of an injunction to remember; the
      wish to witness what took place in the past; direct or indirect suggestive
      influence by the analyst; a defensive identification with the analyst; and the
      analyst's theoretical orientation to reconstruction. Like a screen memory having
      some veridical content yet serving a masking function, a screen construction can
      have elements of truth. At the same time such constructions may function as a
      strong resistance of compromise against intense erotic, sadomasochistic, or
      narcissistic themes in the transference/counter-transference that were painful or
      conflictual in the past. If screen constructions are assumed to be historically
      real or valid, they may not be analyzed for their transferential screening role.
      A previously published case involving a presumably repressed memory of sexual
      molestation is considered from the perspective of the possible development of a
      screen reconstruction. Clinical and scientific aspects of seeking extra-analytic
      confirmation or falsification of reconstructions are discussed.

PMID- 9565904
TI  - A new view of developmental research for psychoanalysts.
AB  - Three major epistemological perspectives in psychoanalysis are summarized, and
      the developmental research relevant to each is described. Not all research is
      useful for all psychoanalytic perspectives. The most historically recent of the
      three perspectives, exemplified by Winnicott, others in the British Independent
      Group, and the "relationists" in the United States, who focus on the experiential
      immediacy of the analyst-analysand interaction and emotions, presents new
      problems and challenges for meaningful dialogue with the developmental
      researcher. Research in extrapsychoanalytic disciplines has traditionally been
      posed as authoritative for the grounding of psychoanalytic "truth," and, unlike
      the earlier perspectives, this view explicity rejects any truth deriving from
      authority outside the psychoanalytic process itself. To illustrate how
      developmental research inquiry would be different for each epistemological
      perspective in psychoanalysis, the same study of infant development is described
      in three different ways as relevant to each perspective. Child development
      research has been changing as a field in ways parallel to psychoanalysis, each
      undergoing fundamental changes that encourage a new integration.

PMID- 9565905
TI  - Maternal identification: a description of the process in real time.
AB  - This research, using the method of microanalysis, explores the to-and-fro
      activity of the self- and object representational world of mothers as they
      observe their children. Under examination is a "moment" usually lasting not more
      than 5-20 seconds that was selected by the mother as outstanding to her during
      the time she was observing her child. A microanalytic interview technique was
      developed in which the mother is asked about everything she experienced about
      "the moment," including what she was feeling, imagining, doing, perceiving, and
      remembering. At brief intervals she was asked to indicate on a scale where--on
      herself or her child--her experience was centered. These data were organized in
      terms of tracking the locus of the mother's perspective: from dwelling in her own
      mind (self-representation) to inhabiting that of her child (object
      representation). Results indicate that these representational shifts occurred
      frequently, usually every one to three seconds, and that there were significant
      individual differences among the mothers.

PMID- 9565907
TI  - Classics revisited: Erik Erikson's childhood and society. Panel report.

PMID- 9565906
TI  - Erikson's concept of ego identity reconsidered.
AB  - This paper explores and attempts to explain the paradox that Erik Erikson--after
      Freud, undoubtedly the psychoanalyst best known, most deeply esteemed, and most
      widely influential in the sociohistorical surround of world culture--has at the
      same time never been properly integrated into the psychoanalytic mainstream, but
      has instead been marginalized, consigned to a persisting psychoanalytic limbo.
      Two successive contexts within the historical unfolding of psychoanalysis in
      America, the milieu in which Erikson worked, would seem to account for this
      neglect. First, Erikson's monumental contributions to our understanding of the
      psychosocial developmental process, of the epigenesis of the ego, of the phase
      specific developmental tasks across the eight postulated stages of the life
      cycle, and of the intergenerational cogwheeling of the life cycles were made
      during the 1950s and 1960s and could not easily be integrated into the ego
      psychology metapsychological paradigm then monolithically regnant within American
      psychoanalysis. And, second, as a major paradigm shift took place in America,
      beginning in the 1970s, toward a more relational, interpersonal, and
      intersubjective framework, Erikson's contributions, couched as they were in the
      structural language of the ego psychology of his time, were overlooked and went
      unremarked as seminal precursors of the newly emerging emphases. The clear
      relationship of Erikson's concepts of (ego) identity to emerging conceptions of
      self in relation to objects was simply not noticed, and his work continues to
      this day to be neglected and unintegrated within psychoanalysis.

PMID- 9565908
TI  - Classics revisited: Erik Erikson's "the dream specimen in psychoanalysis". Panel
      report.

PMID- 9565909
TI  - The relevance of infant observation.

PMID- 9565910
TI  - The irrelevance of Wolff?

PMID- 9565911
TI  - Factors associated with PTSD symptoms following treatment for breast cancer: test
      of the Andersen model.
AB  - The utility of Andersen's (1993, 1994) model of psychologic morbidity following
      cancer treatment for predicting PTSD symptoms in breast cancer survivors (N = 82)
      was examined. PTSD symptoms, physical comorbidity, social support, depression
      history, and pre-cancer traumatic stressors were assessed in a structured
      telephone interview. Multiple regression analysis indicated that Andersen model
      variables (physical comorbidity, education, disease stage, cancer treatment,
      depression history, social support) accounted for 39% of variance in PTSD symptom
      reports (p < .001). Addition to the model of time since treatment completion, pre
      cancer traumatic stressors, age at diagnosis, and tamoxifen usage accounted for
      an additional 16% of variance (p < .001). Higher levels of PTSD symptoms were
      associated with less social support, greater pre-cancer trauma history, less time
      since treatment completion, and more advanced disease.

PMID- 9565912
TI  - Posttraumatic stress disorder and family functioning in adolescent cancer.
AB  - Twenty three adolescents with a history of cancer, 27 physically abused
      adolescents, and 23 healthy, nonabused adolescents were administered structured
      posttraumatic stress disorder (PTSD) interviews and self-report questionnaires
      regarding family functioning. Thirty five percent of adolescent cancer subjects
      met criteria for lifetime PTSD as compared to only 7% of the abused adolescents:
      17% of the cancer subjects and 11% of the abuse subjects met criteria for current
      PTSD. Adolescents with cancer viewed their mothers and fathers as significantly
      more caring and more protective than the comparison and abused adolescents.
      Cancer subjects who met criteria for lifetime PTSD saw their families as
      significantly more chaotic than those who did not have PTSD. Eighty three percent
      of cancer subjects who had lifetime PTSD also had mothers who had PTSD.

PMID- 9565914
TI  - Animal defensive reactions as a model for trauma-induced dissociative reactions.
AB  - Patients with complex dissociative disorders remain in alternating
      psychophysiological states which are discrete, discontinuous, and resistant
      against integrative tendencies. In this contribution, a parallel is drawn between
      animal defensive and recuperative states that are evoked in the face of severe
      threat and the characteristic responses of dissociative disorder patients as
      displayed in major dissociative states. Empirical data and clinical observations
      seem to be supportive of the idea that there are similarities between freezing,
      concomitant development of analgesia and anesthesia, and acute pain in threatened
      animals and severely traumatized human beings.

PMID- 9565913
TI  - Comparative distress levels of inner-city family members of homicide victims.
AB  - This study investigated the distress levels of 150 family members of homicide
      victims, as well as how pre-event, peri-event, and postevent variables were
      related to distress. Distress levels were very high, with 26% of the sample
      reporting clinical distress. Because it was not possible to say if this distress
      resulted from the homicide itself or from the fact that people who lose family
      members to homicide generally have lives rooted in stressful contexts, we
      compared the homicide sample to two sociodemographically comparable groups of 108
      other trauma victims and 119 nonvictims selected from a larger epidemiological
      dataset. Homicide survivors were significantly more distressed than either group,
      suggesting that loss of a family member to homicide has definite clinical
      implications. Although event-related variables were somewhat predictive of
      distress, pre-event and postevent variables selected for this study had greater
      predictive utility.

PMID- 9565915
TI  - The development of a measure of correlates of child sexual abuse: the Traumatic
      Sexualization Survey.
AB  - The present research developed an instrument which assesses cognitive and
      behavioral factors purportedly associated with child sexual abuse histories.
      Finkelhor and Browne's construct of traumatic sexualization served as a guide for
      item selection. The study resulted in a 38-item reliable measure consisting of
      four subscales: Avoidance and Fear of Sexual and Physical Intimacy, Thoughts
      About Sex, Role of Sex in Relationships, and Attraction/Interest and Sexuality.
      Construct validity was established using a variety of self-report instruments
      associated with the dimensions of traumatic sexualization. Sexually abused women
      scored higher than nonabused women on three TSS factors. Physically abused women
      differed from nonabused women on only one factor. Sexually abused women did not
      score significantly higher than physically abused women on any factors.

PMID- 9565916
TI  - Dysfunctional cognitions and adult psychological functioning in child sexual
      abuse survivors.
AB  - Two studies explored the relationship between cognitions and long-term symptoms
      in adult child sexual abuse (CSA) survivors. In Study 1, an American sample of 43
      survivors completed questionnaires assessing attributional style and
      dysfunctional beliefs in cognitive themes affected by victimization, as well as
      measures of posttraumatic symptoms. Survivors' attributions of negative events
      were more internal, stable, and global than those of 29 comparison subjects
      without a history of CSA. However, only the globality scale was significantly
      related with severity of long-term symptoms. High correlations between
      dysfunctional beliefs concerning safety, trust, esteem, or intimacy, and
      posttrauma symptoms were found. The latter finding was replicated in Study 2 with
      a German sample of 35 CSA survivors, even when controlling for frequency of
      abuse.

PMID- 9565917
TI  - Recovered memory of childhood sexual trauma: a documented case from a
      longitudinal study.
AB  - A case of recovered memory of childhood trauma is reported with documented sexual
      trauma in early childhood, chronicled evidence of the absence of memory for
      traumatic experience over a period of time, and substantial evidence of
      'spontaneous' recovery of memory. This account contains the first available
      prospective report of memory loss in a case in which there is both documented
      evidence of trauma and evidence of recovery of memory. The case emerged as part
      of a broadband, large-scale study of children followed closely from birth to
      adulthood which was not focused on memory for trauma. Prospective data gathered
      in a neutral research context, corroborated and supplemented by retrospective
      information, circumvent many limitations of previous retrospective accounts of
      recovered memories.

PMID- 9565918
TI  - Structural aspects of survivors' thinking about the Holocaust.
AB  - Videotaped interviews of 30 Holocaust survivors were scored for integrative
      complexity, the recognition of alternate perspectives or dimensions of a topic
      ("differentiation") and the joint consideration of several perspectives or
      dimensions ("integration"). Memories showed decreased differentiation and
      integration as they moved from pre-war life to the shock and upheaval when
      organized persecution began. High complexity levels reflected survivors mustering
      their resources to enhance their chances of survival and successful postwar
      adaptation. These findings demonstrate the usefulness of quantitative, objective
      content analytic methods in Holocaust survivor research, add a cognitive
      dimension to the study of survival during and after extreme situations, and
      confirm theoretical propositions about decision making and information processing
      under stress.

PMID- 9565919
TI  - Effects of litigation settlements on posttraumatic stress symptoms in motor
      vehicle accident victims.
AB  - In order to investigate the effects of the initiation of litigation and its
      settlement on victims of motor vehicle accidents (MVAs), we followed up 132 MVA
      victims from an initial assessment 1 to 4 months post-MVA for 1 year. Of the 67
      who had initiated litigation, 18 (27%) settled within the 12 months, while 49
      still had litigation pending; 65 never initiated litigation. Those who initiated
      litigation had more severe injuries and higher initial levels of posttraumatic
      stress (PTS) symptoms. All three groups improved in major role function and had
      reduced PTS symptoms over the 1 year follow-up. Those whose suits were still
      pending, as well as those whose suits had been settled, showed no reduction in
      measures of anxiety or depression, whereas the nonlitigants did show improvement
      on these measures.

PMID- 9565920
TI  - MMPI scales for diagnosing acute and chronic PTSD in civilians. Minnesota
      Multiphasic Personality Inventory.
AB  - To develop new Minnesota Multiphasic Personality Inventory (MMPI) scales for
      diagnosing acute and chronic posttraumatic stress disorder (PTSD), 237 civilians
      with PTSD or panic disorder (controls) completed the MMPI-R. All 399 items were
      submitted to chi-square analysis to select those differentiating acute or chronic
      PTSD from controls. The analyses yielded an MMPI Acute PTSD scale (32 items) and
      a MMPI Chronic PTSD scale (41 items). Discriminating between acute PTSD and
      controls, the MMPI Acute PTSD scale had a hit rate of 83% and the MMPI Chronic
      PTSD scale produced a hit rate of 75% to 80%. Cross-validation produced similar
      hit rates. These scales scores were not substantially influenced by gender or
      types of traumatic events, and only the MMPI Acute PTSD scale seemed to not be
      sensitive to co-morbidity.

PMID- 9565921
TI  - Female partners' estimations of male veterans' combat-related PTSD severity.
AB  - This study investigated concordance between male Vietnam veterans' and their
      female partners' reports of veterans' posttraumatic stress disorder (PTSD)
      symptoms. Fifty male Vietnam combat veterans and their partners rated the
      severity of their own PTSD symptoms. Also, partners rated the severity of
      veterans' symptoms. Results indicated modest levels of agreement in reports of
      symptom presence/absence. Partner ratings of veterans' PTSD severity were
      positively correlated with veteran reports and partners' own self-reported PTSD
      symptoms. After controlling for veterans' self-reported symptoms, partners'
      symptoms significantly predicted their estimates of veterans' avoidance symptoms,
      but not veterans' reexperiencing or hyperarousal symptoms. Theoretical and
      practical implications of these findings are discussed.

PMID- 9565922
TI  - The development of a scale to assess war-time atrocities: the War Events Scale.
AB  - The War Events Scale (WES) was developed to assist clinicians with the assessment
      of war zone veterans' exposure to, and participation in war-time atrocities
      distinct from combat, and their current distress from these events. Data
      concerning content validity, test-retest reliability, internal consistency, as
      well as correlational data with the Combat Exposure Scale and the Mississippi
      Scale are presented. Results indicate that the WES does have adequate internal
      consistency and test-retest reliability, and correlates moderately with the
      Combat Exposure and Mississippi Scales. Initial results suggest that the WES may
      be helpful in collecting extremely sensitive information concerning the exposure
      of war zone veterans to atrocities.

PMID- 9565923
TI  - Relationship between trauma narratives and trauma pathology.
AB  - In this study we examined the relationship between posttrauma pathology and the
      level of articulation (complexity) in rape narratives recounted by victims
      shortly after the assault. Degree of articulation was operationalized as the
      reading level of the narrative as determined by a computer program. Shortly after
      the trauma, reading level was correlated with severity of anxiety but not with
      posttraumatic stress disorder (PTSD) symptoms. Degree of the narrative
      articulation shortly after the trauma, however, was related to severity of later
      PTSD. These results are consistent with the hypothesis that the less developed
      trauma narratives hinder recovery from trauma.

PMID- 9565924
TI  - Screening for PTSD in a substance abuse sample: psychometric properties of a
      modified version of the PTSD Symptom Scale Self-Report. Posttraumatic stress
      disorder.
AB  - The high rate of posttraumatic stress disorder (PTSD) among substance use
      disorder (SUD) patients has been documented in research protocols, but there is
      evidence that it is markedly under-diagnosed in clinical settings. To address the
      need for a brief self-report measure to identify SUD patients who may benefit
      from further assessment and/or treatment for PTSD, the psychometric properties of
      a modified version of the PTSD Symptom Scale Self-Report (PSS-SR) were examined
      in a treatment-seeking SUD sample (N = 118). The modified version of the PSS-SR,
      which measures both frequency and severity of PTSD symptoms, demonstrated good
      internal consistency reliability and was correlated with other self-report
      measures of trauma-related symptomatology. Comparisons between a structured PTSD
      diagnostic interview and the modified PSS-SR indicated that 89% of the PTSD
      positive patients were correctly classified by the modified PSS-SR. The clinical
      relevance of these findings was discussed.

PMID- 9565925
TI  - Aerobic exercise as therapy for cancer fatigue.
AB  - PURPOSE: Fatigue and impairment of physical performance are common and severe
      problems of cancer patients. We describe the effect of an aerobic exercise
      program designed for cancer patients suffering from these symptoms. METHODS: Five
      cancer patients (4 female, 1 male, age 18 to 55), participated in the training
      program. Fatigue had been present for a time ranging between 5 wk and 18 months
      and hindered the patients from carrying out normal daily activities. The training
      program consisted of walking daily on a treadmill with an intensity corresponding
      to a lactate concentration of 3 +/- 0.5 mmol.L-1 and was carried out for 6 wk.
      RESULTS: By the end of the exercise program we observed an improvement in maximal
      physical performance (from 6.4 +/- 0.4 km.h-1 to 7.5 +/- 0.9 km.h-1, P < 0.05)
      and maximal walked distance (from 1640 +/- 724 m to 3300 +/- 953 m, P < 0.05).
      Heart rate and lactate concentration by an equivalent submaximal workload (5 km.h
      1) were significant reduced (from 138 +/- 21 beats.min-1 to 113 +/- 20 beats.min
      1, P < 0.05, and from 2.6 +/- 1.4 mmol.L-1 to 1.3 +/- 0.6 mmol.L-1, P < 0.05);
      all patients experienced a clear reduction of fatigue and could carry out normal
      daily activities again without substantial limitations. CONCLUSION: We conclude
      that an aerobic exercise program of precisely defined intensity, duration, and
      frequency can be prescribed as therapy for primary fatigue in cancer patients.

PMID- 9565926
TI  - Comparison of dyspnea ratings during submaximal constant work exercise with
      incremental testing.
AB  - PURPOSE: The purpose of this study was to determine whether dyspnea ratings would
      be similar during submaximal (as used for training) and incremental (as used in
      testing) exercise at specific intensities in patients with chronic obstructive
      pulmonary disease (COPD). METHODS: We studied 20 patients with COPD. Age was 66
      +/- 9 yr (mean +/- SD); FEV1 was 43 +/- 14% pred. At Visit 1 patients provided
      dyspnea ratings (0 to 10 scale) each minute during incremental exercise on the
      cycle ergometer. At Visit 2 patients rated dyspnea during production of
      submaximal exercise for 10 min at two intensities. RESULTS: Peak oxygen
      consumption (VO2) was 13.9 +/- 3.2 mL.kg-1.min-1. At visit 2 VO2 was stable, but
      dyspnea ratings increased slightly. Dyspnea ratings (2.0 +/- 1.2) during
      submaximal exercise were higher than during incremental exercise (1.1 +/- 0.7) at
      55 +/- 8% of peak VO2 (P = 0.02) but were similar (4.3 +/- 1.5 vs 3.9 +/- 1.5) at
      77 +/- 8% of peak VO2 (P = 0.40). CONCLUSIONS: In patients with COPD, dyspnea
      ratings were similar during steady state compared with equivalent levels of
      incremental exercise at a "high" intensity, but were slightly higher at the "low"
      exercise intensity. These data support the potential use of dyspnea ratings
      obtained during incremental exercise as a target for exercise training in
      patients with respiratory disease.

PMID- 9565927
TI  - Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant
      recipients.
AB  - PURPOSE: To determine the effect of resistance exercise training (ET) on
      glucocorticoid-induced myopathy in heart transplant recipients (HTR), 14 male HTR
      were randomly assigned to a ET group that trained for 6 months (54 +/- 3 yr old;
      mean +/- SD) or a control group (51 +/- 8 yr old; mean +/- SD). METHODS: Fat
      mass, fat-free mass, and total body mass were measured by dual-energy x-ray
      absorptiometry before and 2 months after transplantation (Tx), and after 3 and 6
      months of ET or control period. The exercise regimen consisted of lumbar
      extension (MedX) performed 1 d.wk-1 and variable resistance exercises (Nautilus)
      performed 2 d.wk-1. PreTx body composition did not differ between groups.
      RESULTS: At 2 months after Tx, fat-free mass was significantly decreased below
      baseline in both control (-3.4 +/- 2.1%) and ET groups (-4.3 +/- 2.4%). Fat mass
      was significantly increased at 2 months after Tx in both the control (+8.3 +/-
      2.8%) and ET groups (+7.3 +/- 4.0%). Six months of ET restored fat-free mass to
      levels 3.9 +/- 2.1% greater (P < or = 0.05) than before Tx. Fat-free mass of the
      control group decreased progressively to levels that were 7 +/- 4.4% lower than
      preTx values (P < or = 0.05). Both groups increased knee extension, chest press,
      and lumbar extensor strength, but improvements in the ET group were four- to six
      fold greater (P < or = 0.05). CONCLUSION: Our results demonstrate that
      glucocorticoid-induced changes in body composition in HTR occur early after Tx.
      However, 6 months of specific ET restores fat-free mass to levels greater than
      before Tx and dramatically increases skeletal muscle strength. Resistance
      exercise, as part of a strategy to prevent steroid-induced myopathy, appears to
      be safe and should be initiated early after heart Tx.

PMID- 9565928
TI  - Muscle metaboreceptor modulation of cutaneous active vasodilation.
AB  - PURPOSE: Isometric handgrip exercise in hyperthermia has been shown to reduce
      cutaneous vascular conductance (CVC) by inhibiting the cutaneous active
      vasodilator system. METHODS: To identify whether this response was initiated by
      muscle metaboreceptors, in seven subjects two 3-min bouts of isometric handgrip
      exercise in hyperthermia were performed, followed by 2 min of postexercise
      ischemia (PEI). An index of forearm skin blood flow (laser-Doppler flowmetry) was
      measured on the contralateral arm at an unblocked site and at a site at which
      adrenergic vasoconstrictor function was blocked via bretylium iontophoresis to
      reveal active cutaneous vasodilator function unambiguously. Sweat rate was
      measured via capacitance hygrometry, CVC was indexed from the ratio of skin blood
      flow to mean arterial pressure and was expressed as a percentage of maximal CVC
      at that site. In normothermia, neither isometric exercise nor PEI affected CVC (P
      > 0.05). RESULTS: The first bout of isometric handgrip exercise in hyperthermia
      reduced CVC at control sites and this reduction persisted through PEI (pre
      exercise: 59.8 +/- 5.4, exercise: 49.8 +/- 4.9, PEI: 49.7 +/- 5.3% of maximum;
      both P < 0.05), whereas there were no significant changes in CVC at the bretylium
      treated sites. The succeeding bout of isometric exercise in hyperthermia
      significantly reduced CVC at both untreated (pre-exercise: 59.0 +/- 4.8,
      exercise: 47.3 +/- 4.0, PEI: 50.1 +/- 4.1% of maximum; both P < 0.05) and
      bretylium treated sites (pre-exercise: 61.4 +/- 7.3, exercise: 50.6 +/- 5.1, PEI:
      53.9 +/- 6.0% of maximum, both P < 0.05). At both sites, CVC during PEI was lower
      than during the pre-exercise period (P < 0.05). Sweat rate rose significantly
      during both bouts of isometric exercise and remained elevated during PEI.
      CONCLUSIONS: These data suggest that the reduction in CVC during isometric
      exercise in hyperthermia, including the inhibition of the active vasodilator
      system, is primarily mediated by muscle metaboreceptors, whereas central command
      or muscle mechanoreceptors have less influence.

PMID- 9565929
TI  - Relationships between fluid and electrolyte hormones and plasma volume during
      exercise with training and detraining.
AB  - PURPOSE: The purpose of this study was to investigate the relationship between
      training-induced alterations in plasma volume (PV) and changes in fluid and
      electrolyte regulatory hormones during prolonged exercise. METHODS: Seven male
      subjects (VO2peak 49.2 +/- 2.4 mL.kg-1.min-1, X +/- SE) performed a cycling test
      before (C) and after (T) 6 d of training and after 6 d of detraining (DT).
      Training was conducted for 2 h.d-1 at 68% VO2peak at a room temperature between
      26-28 degrees C. The 60-min exercise challenge included 20 min at 50%, 65%, and
      75% VO2peak workloads. RESULTS: Training resulted in a calculated 13.8 +/- 1.6%
      PV expansion (P < 0.05) which recovered to C levels with DT (1.8 +/- 2.3%, P >
      0.05). Compared with that at C, training resulted in a reduction of aldosterone
      (ALDO) concentration at all exercise intensities (P < 0.05) which normalized to C
      levels with DT. With T, epinephrine (EPI) concentrations were reduced at the
      highest power output only (365 +/- 51 vs 113 +/- 22 pg.mL-1; P < 0.05) and
      returned to C levels with DT. Arginine vasopressin (AVP) concentrations were also
      reduced at the highest workload only (20.2 +/- 3.2 pg.mL-1 vs 10.4 +/- 0.7 pg.mL
      1; P < 0.05) and remained depressed after DT (11.8 +/- 1.3 pg.mL-1; P < 0.05).
      Atrial natriuretic factor (ANF) and norepinephrine (NOREPI) were not affected by
      T or DT. CONCLUSIONS: The results suggest that concentrations of ALDO, and to a
      lesser extent EPI, during exercise are related to PV levels, whereas ANF and
      NOREPI concentrations are not. AVP concentrations are related to other adaptive
      factors, the effects of which persist for a longer time course than do PV
      changes.

PMID- 9565930
TI  - High frequency diaphragmatic fatigue detected with paired stimuli in humans.
AB  - PURPOSE: The purpose of this study was to determine whether high frequency
      fatigue was present in the diaphragm after intense whole body endurance exercise.
      METHODS: We used bilateral phrenic nerve stimulation (BPNS) before and during
      recovery from whole body exercise to detect fatigue in the diaphragm. To detect
      high frequency fatigue we used paired stimuli at 10, 20, 50, 70, and 100 Hz
      frequency and determined the transdiaphragmatic pressure (Pdi) response to the
      second stimulation (T2). RESULTS: The subjects (N = 10) exercised at 93.3 +/-
      2.3% of their VO2max for 9.9 +/- 0.5 min. The Pdi response to "twitch" and 10 Hz
      "tetanic" stimulation was decreased immediately after exercise versus pre
      exercise values (-23.4 +/- 3.3%). The T2 amplitude was substantially reduced at
      all frequencies immediately after exercise (-28.0%), but by 30 min into recovery
      the T2 amplitude at 70 and 100 Hz was not different from pre-exercise values. In
      contrast, at 10 and 20 Hz the T2 response was still significantly reduced.
      CONCLUSIONS: We interpret these data to mean that high frequency fatigue as well
      as low frequency fatigue were present in the diaphragm after intense whole body
      endurance exercise.

PMID- 9565931
TI  - Peak oxygen uptake, muscle volume, and the growth hormone-insulin-like growth
      factor-I axis in adolescent males.
AB  - PURPOSE: The growth effects of exercise appear to be mediated in part by central
      neuroendocrine control reflected in circulating levels of growth hormone (GH),
      insulin-like growth factor-I (IGF-I), and their binding proteins (BP). In
      previous studies positive correlations between peak VO2 and circulating IGF-I
      have been demonstrated. The relationship between peak oxygen uptake and these
      potential regulating factors has not been examined in adolescent males where
      patterns of GH pulsatility and levels of IGF-I are rapidly changing. METHODS:
      Forty-three healthy adolescent males (age 16 +/- 0.7 yr, 70% at Tanner V)
      performed cycle ergometry to determine p oxygen uptake (peak VO2), and magnetic
      resonance images to determine the thigh muscle volume. Baseline blood samples
      were collected for GHBP, the extracellular portion of the GH tissue receptor (by
      ligand mediated immunofunctional assay), IGF-I (by RIA), and IGFBPs 1-5 (by RIA).
      Mean GH was determined from samples obtained every 20 min overnight. RESULTS:
      Peak VO2/kg was positively correlated with mean overnight GH levels (r = 0.41, P
      < 0.005). Both peak VO2/kg and thigh muscle volume/kg were negatively correlated
      with GHBP (r = -0.33, P < 0.02) and IGFBP-4 (r = -0.52, P < 0.005). There were no
      correlations between peak VO2/kg and IGF-I or IGFBPs 1-3, and 5. CONCLUSIONS: GH
      pulsatility is increased adolescent males who have higher peak VO2, but this did
      not translate into increases in IGF-I. We speculate that in the fitter males,
      lower GHBP levels may reduce hepatic sensitivity to GH. Thus, circulating IGF-I
      was unchanged despite higher mean GH in subjects with higher peak VO2. IGFBP-4
      which is known to inhibit IGF-I was negatively correlated with peak VO2 leading,
      possibly, to increased IGF-I bioactivity. Fitness (as assessed by muscle mass and
      peak VO2) does modulate the GH-IGF-I axis, but not solely through circulating IGF
      I; both GHBP and IGFBPs play important roles.

PMID- 9565932
TI  - Effect of weight training exercise and treadmill exercise on post-exercise oxygen
      consumption.
AB  - Effect of weight training exercise and treadmill exercise on postexercise oxygen
      consumption. Med. Sci. Sports Exerc., Vol. 30, No. 4, pp. 518-522, 1998. To
      compare the effect of weight training (WT) and treadmill (TM) exercise on
      postexercise oxygen consumption (VO2), 15 males (mean +/- SD) age = 22.7 +/- 1.6
      yr; height = 175.0 +/- 6.2 cm; mass = 82.0 +/- 14.3 kg) performed a 27-min bout
      of WT and a 27-min bout of TM exercise at matched rates of VO2. WT consisted of
      performing two circuits of eight exercises at 60% of each subject's one
      repetition maximum with a work/rest ratio of 45 s/60 s. Approximately 5 d after
      WT each subject walked or jogged on the TM at a pace that elicited an average VO2
      matched with his mean value during WT. VO2 was measured continuously during
      exercise and the first 30 min into recovery and at 60 and 90 min into recovery.
      VO2 during WT (1.58 L.min-1) and TM exercise (1.55 L.min-1) were not
      significantly (P > 0.05) different; thus the two activities were matched for VO2.
      Total oxygen consumption during the first 30 min of recovery was significantly
      higher (P < 0.05) as a result of WT (19.0 L) compared with that during TM
      exercise (12.7 L). However, VO2 values at 60 (0.32 vs 0.29 L.min-1), and 90 min
      (0.33 vs 0.30 L.min-1) were not significantly different (P > 0.05) between WT and
      TM exercise, respectively. The results suggest that, during the first 30 min
      following exercise. WT elicits a greater elevated postexercise VO2 than TM
      exercise when the two activities are performed at matched VO2 and equal
      durations. Therefore, total energy expenditure as a consequence of WT will be
      underestimated if based on exercise VO2 only.

PMID- 9565933
TI  - Effect of induced alkalosis on exhaustive leg press performance.
AB  - PURPOSE: Fifteen males were studied before, during, and in recovery from
      exhaustive resistance exercise 105 min after ingesting 0.3 g.kg-1 of either a
      placebo (white flour) or sodium bicarbonate (NaHCO3). METHODS: The exercise
      consisted of five maximal sets on a leg press machine, The load was adjusted to
      maintain the number of repetitions per set for each subject at approximately 12
      repetitions. A significant (P < 0.05) increase in pH (7.40 to 7.47), oxygenated
      base excess (OxyBE) (-1.3 to 4.0 mEq.L-1), and bicarbonate concentration ([HCO3
      ]) (22.8 to 27.4 mM) was achieved before exercise with the ingestion of NaHCO3.
      RESULTS: The exercise protocol produced significant changes in acid base status
      consistent with metabolic acidosis for both trials (pH sets 1-5: placebo, 7.4 to
      7.26; NaHCO3, 7.47 to 7.33), (OxyBE sets 1-5: placebo, -1.3 to -12.3 mEq.L-1;
      NaHCO3, 4.0 to -6.9 mEq.L-1) and ([HCO3-] sets 1-5: placebo, 22.9 to 14.0 mM;
      NaHCO3, 27.4 to 17.6 mM). After every set; pH, OxyBE, and [HCO3-] were
      significantly higher in the NaHCO3 trial. Blood lactate concentration ([La-])
      significantly increased throughout exercise for both trials ([La-] sets 1-5:
      placebo, 4.6 to 11.3 mM; NaHCO3, 4.8 to 13.4 mM). After sets 4 and 5, blood [La-]
      was significantly higher in the NaHCO3 trial. Bicarbonate ingestion did not
      improve performance (total repetitions: NaHCO3 = 59 +/- 3; placebo = 60 +/- 2).
      CONCLUSIONS: This may be a result of a lower demand on the whole body metabolic
      system in comparison with that for other modes of exercise in which ergogenic
      effects have been found.

PMID- 9565934
TI  - Relationship between muscle swelling and stiffness after eccentric exercise.
AB  - PURPOSE: The time courses of muscle compartmental swelling and passive stiffness
      change were measured to determine whether muscle compartmental swelling accounted
      for increased stiffness. METHODS: Eleven untrained female college students
      exercised eccentrically by lowering a weight with their elbow flexors.
      Measurements of muscle compartment volume, stiffness, relaxed elbow angle,
      circumference, and pain were recorded before exercise, immediately after
      exercise, and 1-5, 7, 9, and 11 d after exercise. Muscle compartment volume was
      calculated from cross-sectional ultrasound images taken along the upper arm.
      Stiffness was measured using a device that extended the elbow and recorded the
      torque required to hold the forearm at successive angles. RESULTS: Elbow flexor
      volume increased gradually to peak on the fourth day (26.1 +/- 4.3%, P < 0.05)
      and then decreased to baseline values over days 7-11. Stiffness increased
      immediately after exercise (59.9 +/- 14.1%, P < 0.05) and remained at or above
      this level until decreasing to pre-exercise levels over days 7-11. CONCLUSIONS:
      This suggests that muscle swelling does not account for the sudden increase in
      stiffness of the elbow flexor muscles within the first 48 h after exercise but
      may play a role in the subsequent time course of stiffness.

PMID- 9565935
TI  - Lactate influx into red blood cells from trained and untrained human subjects.
AB  - PURPOSE: The purpose of this study was to compare the fractional contributions of
      the three pathways of lactate transport (band 3 system, nonionic diffusion, and
      monocarboxylate pathway) into red blood cells (RBC) from trained and untrained
      humans. METHODS: Blood samples were obtained from 19 male subjects: 5 untrained,
      5 aerobically-trained, 5 competitive collegiate cross-country runners, and 4
      competitive collegiate sprinters. The influx of lactate into the RBC was measured
      by a radioactive tracer technique using [14C]lactate. Discrimination of each
      pathway of lactate transport was achieved by using PCMBS (1 mM) to block the
      monocarboxylate pathway and DIDS (0.2 mM) to block the band 3 system. Nonionic
      diffusion was calculated as the difference between total lactate influx and the
      sum of band 3 and monocarboxylate lactate influx. RESULTS: Total lactate influx
      into the RBC from the more aerobic individuals (trained subjects and cross
      country runners) was significantly faster at 1.6 mM lactate concentration ([La])
      as compared with the influx into RBC of the untrained subjects. Total influx of
      lactate was significantly higher (P < 0.05) in the RBC from the sprinters as
      compared with that in the RBC from the untrained subjects at 41 mM [La]. There
      were no significant differences among the four groups with regard to the total
      influx of lactate at 4.1, 8.1, and 20 mM [La]. In general, the percentage of
      total lactate influx accounted for by each of the three parallel pathways at 1.6,
      8.1, and 41.0 mM [La] was not different among the four groups of subjects.
      CONCLUSIONS: Overall, the groups were more similar than different with regard to
      RBC lactate influx.

PMID- 9565936
TI  - Physical activity and lipids and lipoproteins in American Indians ages 45-74.
AB  - PURPOSE: The Strong Heart Study is a study of cardiovascular disease and its risk
      factors among American Indian men and women aged 45-74 yr representative of 13
      communities from Arizona (AZ), Oklahoma (OK), and North/South Dakota (N/SD). This
      investigation sought to characterize the amount and type of physical activity and
      to determine the association between activity and lipids in this population.
      METHODS: Total physical activity (occupational plus leisure) was assessed with a
      validated questionnaire. RESULTS: Men and women from OK (21 +/- 19 and 16 +/- 15
      h.wk-1; respectively) and N/SD (23 +/- 21 and 17 +/- 17 h.wk-1; respectively) had
      activity levels that were similar if not lower than the U.S. population with the
      AZ communities (17 +/- 21 and 10 +/- 14 h.wk-1; respectively) being substantially
      lower than the other two communities. Total cholesterol (TC), high density
      lipoprotein cholesterol (HDL-c), and low density lipoprotein cholesterol (LDL-c)
      levels were lower than the U.S. population. CONCLUSIONS: For most of the
      population (diabetic men and nondiabetic men and women), activity was
      significantly associated (P < 0.05) with apolipoprotein (apo) AI after
      controlling for covariates. With levels of activity as low if not lower than the
      general U.S. population coupled with high prevalence of obesity and diabetes,
      efforts to increase physical activity in American Indians are warranted.
      Hopefully these increases in activity will result in favorable lipid changes as
      well as decreasing the risk of diabetes which is epidemic in these populations.

PMID- 9565937
TI  - Effect of shoe insert construction on foot and leg movement.
AB  - PURPOSE: The purpose of this study was to quantify changes in foot eversion and
      tibial rotation during running resulting from systematic changes of material
      composition of five shoe inserts of the same shape. METHODS: Tests were performed
      with 12 subjects. The inserts had a bilayer design using two different materials
      at the top and bottom of the insert. The functional kinematic variables examined
      in this study were the foot-leg in-eversion angle, beta, and the leg-foot tibial
      rotation, rho. Additionally, the subject characteristics of arch height, relative
      arch deformation, and active range of motion were quantified. The statistical
      analysis used was a two way repeated measures MANOVA (within trials and inserts).
      RESULTS: The average group changes resulting from the studied inserts in total
      shoe eversion, total foot eversion, and total internal tibial rotation were
      typically smaller than 1 degree when compared with the no-insert condition and
      were statistically not significant. The measured ranges of total foot eversion
      for all subjects were smallest for the softest and about twice as large for the
      hardest insert construction. Thus, the soft insert construction was more
      restrictive, forcing all feet into a similar movement pattern, whereas the harder
      combinations allowed for more individual variation of foot and leg movement and
      did not force the foot into a preset movement pattern. The individual results
      showed substantial differences between subjects and a trend: Subjects who
      generally showed a reduction of tibial rotation with all tested inserts typically
      had a flexible foot. However, subjects who generally showed an increase of tibial
      rotation typically had a stiff foot. CONCLUSIONS: The results of this study
      suggest that subject specific factors such as static, dynamic, and neuro
      physiological characteristics of foot and leg are important to match specific
      feet and shoe inserts optimally.

PMID- 9565938
TI  - Biomechanics of the knee during closed kinetic chain and open kinetic chain
      exercises.
AB  - PURPOSE: Although closed (CKCE) and open (OKCE) kinetic chain exercises are used
      in athletic training and clinical environments, few studies have compared knee
      joint biomechanics while these exercises are performed dynamically. The purpose
      of this study was to quantify knee forces and muscle activity in CKCE (squat and
      leg press) and OKCE (knee extension). METHODS: Ten male subjects performed three
      repetitions of each exercise at their 12-repetition maximum. Kinematic, kinetic,
      and electromyographic data were calculated using video cameras (60 Hz), force
      transducers (960 Hz), and EMG (960 Hz). Mathematical muscle modeling and
      optimization techniques were employed to estimate internal muscle forces.
      RESULTS: Overall, the squat generated approximately twice as much hamstring
      activity as the leg press and knee extensions. Quadriceps muscle activity was
      greatest in CKCE when the knee was near full flexion and in OKCE when the knee
      was near full extension. OKCE produced more rectus femoris activity while CKCE
      produced more vasti muscle activity. Tibiofemoral compressive force was greatest
      in CKCE near full flexion and in OKCE near full extension. Peak tension in the
      posterior cruciate ligament was approximately twice as great in CKCE, and
      increased with knee flexion. Tension in the anterior cruciate ligament was
      present only in OKCE, and occurred near full extension. Patellofemoral
      compressive force was greatest in CKCE near full flexion and in the mid-range of
      the knee extending phase in OKCE. CONCLUSION: An understanding of these results
      can help in choosing appropriate exercises for rehabilitation and training.

PMID- 9565939
TI  - Energy cost of rifle carriage in biathlon skiing.
AB  - PURPOSE: Since biathlon racing involves cross-country skiing while carrying a
      minimum weight 3.5-kg rifle, energy cost for rifle carriage could be significant
      to race outcome. The purposes of this study were to: 1) compare physiological
      measurements of biathletes roller skiing with and without rifle carriage, 2)
      compare energy cost of rifle carriage between women and men, 3) examine the
      relationship of cycle length and cycle rate to energy cost of rifle carriage, and
      4) compare physiological measurements to calculated estimates of power
      requirements of rifle carriage. METHODS: We examined metabolic cost of rifle
      carriage during inclined roller ski-skating. National Team Biathletes (7 W, 8 M)
      performed treadmill roller ski-skating (2.46, 2.68, and 2.91 m.s-1, 8% incline, 5
      min stages) with and without a 3.65 kg rifle. RESULTS: For W, HR, VO2, and VE
      during carriage were higher at all speeds, LA was higher at the fastest speed (P
      < 0.05). For M, VO2 and VE were higher at all speeds, HR and LA were higher at
      2.68 and 2.91 m.s-1 (P < 0.05). Rifle mass as percent of body mass was different
      between W and M (6.6 +/- 0.7% vs 5.0 +/- 0.3%, P < 0.05). Percent increase in VO2
      (2.1% and 1.3% per kg load; for W and M, respectively) was not different than
      rifle mass as percent body wt. Cycle length was related to increased VO2 and LA
      during rifle carriage for W (r = -0.59 and -0.70 to -0.85), and to LA for M (r = 
      0.66 to -0.83). CONCLUSION: The large range in cost between individuals (0.2 +/-
      0.08 and 0.19 +/- 0.17 L.min-1; for W & M, respectively) suggests that individual
      economies for load carriage can be improved.

PMID- 9565940
TI  - Different effects of physical exercise on cold pain sensitivity in fighter pilots
      with and without the history of acute in-flight neck pain attacks.
AB  - PURPOSE: The cold pain sensitivity in fighter pilots was studied by using a cold
      pressor test. METHODS: The pilots were divided into two groups: one group
      consisting of eight pilots (N = 8) who had experienced several acute in-flight
      neck pain attacks, and the control group (N = 8) who had not experienced these
      pain conditions under similar work and environment conditions. In each pilot cold
      pain thresholds and pain and unpleasantness responses to suprathreshold cold
      stimulations were recorded during repeated tests. The ratings of pain and
      unpleasantness responses to cold stimulations were evaluated by visual analog
      scales (VAS). The effect of exercise on cold pain sensitivity was tested in a
      separate experiment. Exercise was performed on a cycle ergometer at different
      workload levels (50-200 W). RESULTS: In the control conditions (resting measures)
      of this study during repeated cold pressor tests, the average pain thresholds and
      pain or unpleasantness responses to suprathreshold cold stimulation were not
      different between groups. Physical exercise increased pain thresholds (P < 0.001)
      in pilots with a history of neck pain attacks but not in control group. Exercise
      induced a significant decrease in pain responses and unpleasantness responses to
      suprathreshold stimulation in both groups. This exercise effect was more marked
      both in pain intensity (P < 0.05) and unpleasantness responses (P < 0.01) in
      pilots with a history of neck pain attacks. Moreover, exercise more markedly (P <
      0.05) decreased unpleasantness than pain intensity responses in both groups of
      pilots. CONCLUSIONS: The results suggest that exercise stress-related analgesia
      mechanisms may be enhanced in pilots with a history of acute in-flight neck pain
      attacks. Moreover, sensory and nonsensory aspects of pain experience may be
      differentially influenced by exercise stress.

PMID- 9565941
TI  - Eating attitudes and energy intakes of female skaters.
AB  - PURPOSE: This study examined potential links between dietary intakes, body
      fatness, menstrual status, and hematological and serum iron status in 21
      competitive female figure skaters aged 11-16 yr. METHODS: Attitudes toward
      dieting were assessed using the Eating Attitudes Test (EAT). Dietary intakes were
      based on 3-d food records. Percent body fat was calculated using measures of
      triceps, subscapular, suprailiac, pectoral, axillary, abdominal, and thigh
      skinfold measures. Blood iron status was measured using hematocrit (Hct),
      hemoglobin (Hgb), total iron binding capacity (TIBC), and serum iron. Menstrual
      status was based on a self-report questionnaire. RESULTS: Body weights and
      estimated energy intakes were all within normal range for this age group. Higher
      EAT scores were associated with lower micronutrient, but not lower energy
      intakes. Menstrual status and iron status were normal. No significant
      correlations between measures of body fatness, menstrual status, and
      hematological or serum iron status were observed. CONCLUSION: Although the
      measured indices of nutritional status were normal, adolescent athletes have
      higher energy needs than does the general population. Depending on energy
      expenditure levels, energy and nutrition intakes in the low normal range may put
      some athletes at risk for undernutrition.

PMID- 9565942
TI  - Role of taste preference on fluid intake during and after 90 min of running at
      60% of VO2max in the heat.
AB  - PURPOSE: The purpose of this study was to determine the relationship between
      taste preference and total fluid intake during a 90-min run at 60% VO2max as well
      as during a 90-min period of seated recovery under hyperthermic conditions (30
      degrees C, 50% RH), comparing the ad libitum intake of water and two carbohydrate
      electrolyte drinks (one containing 6% CHO and the other 8% CHO) randomized over
      three trails. METHODS: Fifteen men runners and triathletes, 18 to 40 yr of age,
      completed an initial test to determine VO2max, a practice 90-min run at 60%
      VO2max, and three experimental 90-min run/90-min recovery trials on separate days
      approximately 1 wk apart. RESULTS: There were no differences across the three
      treatments in fluid intake, rectal temperature, or RPE during exercise, but
      subjects consumed 54% and 59% more fluid during recovery with the two
      carbohydrate-electrolyte drinks compared with water. When comparing the subjects'
      trials with the most liked versus the least liked of the three fluids, they
      consumed more of the most liked fluid during exercise (1.10 vs 0.97 L.90 min-1)
      but not during recovery (1.02 vs 0.90 L.90 min-1.ns). CONCLUSIONS: Thus,
      perceived taste of a beverage is important for fluid replacement during exercise.

PMID- 9565943
TI  - Influence of acute endurance activity on leg neuromuscular and musculoskeletal
      performance.
AB  - PURPOSE: The purpose of this study was to investigate the effect of endurance
      activities designed to simulate the physiological demands of soccer match-play
      and training, on leg strength, electromechanical delay, and knee laxity. METHODS:
      Eight recreational soccer players completed four exercise trials in random order:
      1) a prolonged intermittent high intensity shuttle run (PHISR) which required
      subjects to complete a total distance of 9600 m in a form simulating the pattern
      of physical activity in soccer match-play (activity mode; rest-to-work intervals;
      approximately 90 min duration), 2) a shuttle-run (SR), (3) a treadmill run (TR)
      which required subjects to complete an equivalent distance at a running speed
      corresponding to 70% VO2max, and 4) a control condition consisting of no
      exercise. RESULTS: Results from repeated measures ANOVA revealed significant
      condition (PHISR; SR; TR; control) by time (pre; mid; post) interactions for peak
      torque (PT: knee extension and flexion: 1.05 rad.s-1), EMD and anterior tibio
      femoral displacement (TFD) (P < 0.05). Impairment to indices of knee joint
      performance was observed in PHISR, SR, and TR trials. The greatest decrement
      occurred in PHISR and SR trials (up to 44%). Knee extensor and flexor strength
      performance near to full knee extension (0.44 rad knee flexion) was not changed
      following the functionally-relevant endurance activities. CONCLUSIONS: Even
      though strength performance near to full knee extension was preserved following
      acute endurance activities, the risk of ligamentous injury may be increased by
      concomitant impairment to EMD and anterior TFD.

PMID- 9565944
TI  - Cardiovascular differences between sedentary and wheelchair-trained subjects with
      paraplegia.
AB  - PURPOSE: Heart dimensions, left ventricular function, and internal dimensions of
      limb arteries, as well as physical fitness, were examined in sedentary male
      subjects with paraplegia (SP, N = 20), national elite male athletes with
      paraplegia (PA, N = 29), and untrained able-bodied males (AB, N = 30). METHODS:
      All subjects underwent two-dimensional echocardiography, duplex sonography of
      common femoral artery and subclavian artery at rest, and an incremental
      wheelchair ergometer exercise test. RESULTS: Heart volume in relation to body
      weight was not different in PA as compared with that in AB (11.5 +/- 1.6 vs 11.6
      +/- 2.2 mL.kg-1; mean +/- SD), whereas SP showed significantly lower values (9.7
      +/- 1.5 mL.kg-1). Left ventricular ejection fraction was similar in all subjects
      (59.9-60.8%). In relation to body surface area, subclavian artery cross-sectional
      area was significantly higher in PA compared with that in AB and SP, respectively
      (PA: 0.32 +/- 0.05, AB: 0.21 +/- 0.06, SP: 0.22 +/- 0.05 cm2/m2). The
      corresponding values for the common femoral artery were significantly lower in
      all subjects with paraplegia as compared with those in AB, whereas no difference
      was found between PA and SP (AB: 0.31 +/- 0.05, PA: 0.14 +/- 0.05, SP: 0.15 +/-
      0.04 cm2/m2). Peak oxygen uptake (VO2peak) determined in the wheelchair ergometer
      exercise test was within the same range in PA and AB, but significantly (P <
      0.05) lower in SP (PA: 34.5 +/- 4.3, AB: 31.5 +/- 4.1, SP: 23.9 +/- 3.8 mL.kg
      1.min-1). CONCLUSIONS: In conclusion, cardiac dimensions and VO2peak of PA were
      larger than in SP but do not exceed those of AB. Intensive wheelchair training
      was associated with larger dimensions of the subclavian arteries in PA, whereas a
      hypotrophy of the common femoral artery was found in SP and PA compared with that
      in AB.

PMID- 9565945
TI  - Energetics of best performances in track cycling.
AB  - VO2max and best performance times (BPTs) obtained during maximal voluntary trials
      over 1, 2, 5, and 10 km from a stationary start were assessed in 10 elite
      cyclists. Steady-state VO2 and peak blood lactate concentration ([La]b) were also
      determined in the same subjects pedaling on a track at constant submaximal
      speeds. The energy cost of cycling (Cc, J.m-1) was calculated as the ratio of
      VO2, corrected for glycolytic energy production and expressed in W, to v (m.s-1).
      Individual relationships between Cc and v were described by: Cc = Ccrr + k1 v2
      where Ccrr is the energy spent against friction and k1 v2 is that spent against
      drag. Overall energy cost of cycling (Cctot) was obtained, adding to Cc the
      energy spent to accelerate the total moving mass from a stationary start.
      Individual theoretical BPTs were then calculated and compared with the actual
      ones as follows. The maximal metabolic power sustained at a constant level by a
      given subject (Emax, W) is a known function of the exhaustion time (te). It
      depends on his VO2max and maximal anaerobic capacity; it was obtained from
      individual VO2max and [La]b values. The metabolic power (Ec, W) necessary to
      cover any given distance (d) is a known function of the performance time over d
      (td); it is given by Ec = Cctot v = Cctot d td. For all subjects and distances,
      the t values solving the equalities Emax F(te) = Ec F(td) were calculated and
      assumed to yield theoretical BPTs. Calculations showed a fairly good agreement
      between actual and calculated BPTs with an average ratio of 1.035 +/- 0.058.

PMID- 9565946
TI  - Weight loss patterns and success rates in high school wrestlers.
AB  - PURPOSE: The purposes were to: 1) examine the weight loss patterns in a group of
      high school varsity wrestlers whose teams participated in a body composition
      measurement@nutrition education program, and 2) test the hypothesis that
      wrestling at a weight below recommended Minimum Wrestling Weight (MWW) results in
      decreased wrestling success. METHODS: We measured skinfold thickness in 465
      wrestlers at 16 schools and, using the Lohman method, determined their percent
      body fat. An educational program presented at each school explained the results,
      provided nutritional information regarding proper diet and methods of weight
      loss, and suggested a voluntary MWW corresponding to 5% body fat. After excluding
      the heavyweight wrestlers, there were 159 varsity wrestlers. At the end of the
      season, we noted their weight class and whether they placed in post-season state
      championship qualifying tournaments. RESULTS: We found that 53 wrestlers (33%)
      wrestled below MWW. When analyzed by school, wrestlers' non-adherence to MWW
      ranged from 0% to 56% of all wrestlers. In the lightest four weight classes, 62%
      wrestled below MWW; in the middle four classes, 29%; and in the heaviest four
      classes, 6%. Of the 53 wrestlers below MWW, 57% placed and of the 106 above MWW,
      33% placed (P < 0.01). CONCLUSIONS: These results show that a substantial number
      of wrestlers who participate in a voluntary body fat measurement and diet
      education program wrestle below recommended MWW. This is particularly true at
      lower weight classes. Further, wrestling below MWW was associated with greater
      wrestling success. The current concept of MWW should not be based on wrestling
      performance effects.

PMID- 9565947
TI  - Validity of the computer science and applications (CSA) activity monitor in
      children.
AB  - PURPOSE: The purpose of this study was to evaluate the validity of the CSA
      activity monitor as a measure of children's physical activity using energy
      expenditure (EE) as a criterion measure. METHODS: Thirty subjects aged 10 to 14
      performed three 5-min treadmill bouts at 3, 4, and 6 mph, respectively. While on
      the treadmill, subjects wore CSA (WAM 7164) activity monitors on the right and
      left hips. VO2 was monitored continuously by an automated system. EE was
      determined by multiplying the average VO2 by the caloric equivalent of the mean
      respiratory exchange ratio. RESULTS: Repeated measures ANOVA indicated that both
      CSA monitors were sensitive to changes in treadmill speed. Mean activity counts
      from each CSA unit were not significantly different and the intraclass
      reliability coefficient for the two CSA units across all speeds was 0.87.
      Activity counts from both CSA units were strongly correlated with EE (r = 0.86
      and 0.87, P < 0.001). An EE prediction equation was developed from 20 randomly
      selected subjects and cross-validated on the remaining 10. The equation predicted
      mean EE within 0.01 kcal.min-1. The correlation between actual and predicted
      values was 0.93 (P < 0.01) and the SEE was 0.93 kcal.min-1. CONCLUSION: These
      data indicate that the CSA monitor is a valid and reliable tool for quantifying
      treadmill walking and running in children.

PMID- 9565948
TI  - Accuracy of self-reported exercise and the relationship with weight loss in
      overweight women.
AB  - PURPOSE: The purpose of this study was to compare self-reported exercise to a
      more objective measurement of exercise (i.e., Tri-Trac Accelerometer) and to
      assess whether there is a difference in weight loss between individuals who under
      and over-report their exercise. METHODS: Fifty overweight females (BMI = 34.0 +/
      4.2 kg.m-2) who were participating in a behavioral weight control program were
      included in this study. Subjects were randomly assigned to a long-bout or a short
      bout exercise condition, with both groups instructed to exercise 30 min.day-1 on
      5 d.wk-1 for a period of 20 wk. The long-bout group was to exercise in one
      continuous session (e.g., one 30-min session per day), whereas the short-bout
      group was to divide the exercise into multiple 10-min sessions (e.g., three 10
      min sessions per day). Subjects recorded their exercise in a daily exercise log
      and wore a Tri-Trac accelerometer for a 1-wk period to validate self-reported
      exercise bouts. RESULTS: Results showed that approximately 45% of the women over
      reported the amount of exercise that they performed, and this did not differ
      between the long-bout and short-bout groups. Women who over-reported their
      exercise had significantly poorer weight loss across the 20-wk program than women
      who under-reported their exercise (6.3 +/- 3.6 kg vs 9.4 +/- 5.2 kg).
      CONCLUSIONS: The results of this study suggest that overweight women who over
      report their exercise will have poorer weight loss while enrolled in a behavioral
      weight loss program compared with others enrolled in the program, and the Tri
      Trac Accelerometer may be useful in identifying individuals who inaccurately
      report the amount of their exercise. The ability to classify individuals as
      either over- or under-reporters of their exercise may be helpful to weight loss
      therapists and lead to more successful treatment for obesity.

PMID- 9565949
TI  - Clinical exam of the shoulder.
AB  - This paper outlines the important features of the clinical assessment of the
      shoulder in a systematic and thorough manner. We highlight the key symptoms,
      particularly pain and instability, and describe how they may be associated with
      the various different pathologies. The physical examination is detailed in order
      of inspection, palpation, and motion, and then considerable emphasis is given to
      specific shoulder tests looking for evidence of rotator cuff weakness,
      impingement, biceps pathology, and instability. A number of specific tests of
      instability are outlined including an examination technique for posterior
      instability that has not previously been described.

PMID- 9565950
TI  - Magnetic resonance imaging of the shoulder in the primary care setting.
AB  - MRI is an excellent noninvasive method of diagnosing difficult shoulder problems.
      Although usually not needed for classic primary impingement syndrome or
      clinically obvious rotator cuff tears, MRI may be helpful in diagnosing secondary
      causes of impingement or in some cases involving partial rotator cuff tears. Some
      surgeons may use MRI preoperatively to define the extent of the rotator cuff
      tear, as this may alter their surgical approaches.

PMID- 9565951
TI  - Rotator cuff tendinopathy and subacromial impingement syndrome.
AB  - Subacromial impingement syndrome is one of the most frequently seen causes of
      shoulder pain. The symptoms are often vague and may be difficult to differentiate
      from other shoulder problems. The purpose of this paper is to provide the
      clinician with a more thorough understanding of this entity by reviewing the
      pertinent anatomy and underlying etiology. Suggestions are made to aid in
      establishing the diagnosis, and treatment recommendations are proposed.

PMID- 9565952
TI  - Shoulder instability and impingement in throwing athletes.
AB  - The glenohumeral articulation maintains a fine balance between mobility and
      stability. In the throwing athlete, this balance is stressed from the repetitive
      microtrauma incurred to achieve peak performances. The presentation of shoulder
      pain in the throwing athlete can be confusing, and a thorough understanding of
      anatomy and biomechanics, in addition to the history and physical examination,
      are necessary to delineate the correct diagnosis. Specifically, differentiating
      between instability and impingement is critical to initiate appropriate
      nonoperative and operative interventions. This paper discusses the anatomy and
      biomechanics in the shoulder and provides a comprehensive approach to evaluate
      anterior shoulder pain in throwing athletes. In addition, treatment options will
      be discussed with specific emphasis or nonoperative interventions.

PMID- 9565953
TI  - Acromioclavicular joint disorders.
AB  - The acromioclavicular joint is commonly involved in athletic injuries. Most
      commonly, a sprain to the joint occurs with variability in the amount of
      ligamentous damage and displacement that occurs. In all but the most severe
      dislocations, treatment consists of initial sling immobilization and early
      functional rehabilitation. The outcome is usually excellent with full return of
      function following these injuries. The rarer types (IV, V, and VI) require
      operative reduction and fixation. Distal clavicle fractures are related injuries,
      which many times disrupt the stabilizing ligaments of the acromioclavicular
      joint. Many can be treated nonoperatively, but there are several subtypes that
      should be considered for early fixation to reduce complications of pain and
      shoulder dysfunction. An atraumatic, overuse condition, which is becoming more
      prevalent and seems related to weight training, is osteolysis of the distal
      clavicle. There is insidious onset of shoulder pain with symptoms and signs
      consistent with acromioclavicular pathology. Activity modification is the best
      method of controlling symptoms. Failure of the conservative approach necessitates
      operative excision of the distal clavicle.

PMID- 9565954
TI  - Frozen shoulder syndrome: diagnostic and treatment strategies in the primary care
      setting.
AB  - The term "frozen shoulder" has been used to describe an array of clinical
      conditions. The authors consider a patient as meeting the criteria of primary or
      secondary frozen shoulder syndrome if he/she has a clinical history of worsening
      painful shoulder motion loss of at least 1 month duration and a physical
      examination documenting painful restricted shoulder motion. In the evaluation of
      the patient with suspected FSS, initial screening shoulder radiographs are
      required to exclude other conditions. The physical examination of the frozen
      shoulder patient should include observation, cervical examination, assessment of
      range of motion, and the use of provocative testing. The treatment of the patient
      with FSS should include preventative education, various medications including
      NSAIDS and oral corticosteroids, physical therapy, and finally, for the patient
      with refractory symptoms, surgical intervention. For those patients necessitating
      surgical intervention, the authors recommend a selective arthroscopic capsular
      release.

PMID- 9565955
TI  - Shoulder rehabilitation: principles and practice.
AB  - The goal of shoulder rehabilitation is to restore the function of the shoulder.
      Function can be described in many different ways, but the framework for
      restoration of function should include restoration of the anatomy plus
      normalization of physiology and biomechanics. Without the normalization of
      physiology and biomechanics, the shoulder will not function in a normal fashion.
      Most of the methods and practice of shoulder rehabilitation are involved in
      strategies to normalize physiology and biomechanics of the shoulder motion. This
      study will review the physiology and biomechanics of normal shoulder function and
      then describe basic principles and clinical practices to restore those functions.

PMID- 9565956
TI  - Experimental laparoscopic and thoracoscopic discectomy and instrumented spinal
      fusion. A feasibility study using a porcine model.
AB  - To explore the safety and the effectiveness of laparoscopic and thoracoscopic
      spinal surgery, an acute/non-survival animal trial was performed in 5 pigs using
      rigid and flexible endoscopes, flouroscopy, a holmium-YAG laser, and prototype
      instruments and implants. Our study aimed to approach the intervertebral disc
      space and spinal canal using laparoscopic and thoracoscopic techniques and to
      explore the potential and limits for endoscopic anterior spinal decompression and
      fusion. In a lateral recumbency access was provided to the anterolateral aspect
      of the lumbar spine from L1/2 to L7/S1, the thoracic spine was accessible from
      T2/3 to the diaphragmatic insertion. Complete disc space emptying with
      penetration into the spinal canal could be performed, epidural bleeding could be
      controlled by a hemostatic sponge, however bleeding restricted visualization for
      further endoscopic manipulation in the spinal canal. Intervertebral fusion was
      accomplished at T6/7, L4/5 and L7/S1 using small fragment plates with 3.5 mm
      screws and iliac bone grafts or prototype carbon fiber cages. On post mortem
      examination we found no dural tears and no nerve root damage, all animals had
      stabilized fusion sites and good implant position. We conclude that minimally
      invasive thoracoscopic and laparoscopic approaches to the spine are feasible and
      safe to perform disc decompression and implant placement for spinal fusion. In
      addition to currently performed laparoscopic interbody fusion, also plate
      fixation to reestablish lordosis of the lumbar spine is feasible at least in the
      porcine model. Careful disc decompression must be performed prior to implant
      introduction to prevent iatrogenic disc protrusion and spinal cord or nerve root
      compression. However, further surgical exploration of the spinal canal using
      these techniques does not provide adequate visualization of epidural spaces and
      therefore must be regarded as unsafe.

PMID- 9565957
TI  - Endoscopic laser foraminoplasty on the lumbar spine--early experience.
AB  - Since April 1995 this endoscope assisted laser technique has been used for
      widening the lumbar exit route foramina. Patient selection included individuals
      with primarily unilateral sciatica as well as low back pain and referred buttock
      pain following various operative interventions. Endoscopic laser foraminoplasty
      (ELF) utilises an endoscope, a uniportal posterolateral approach and a side
      firing holmium laser probe. Under direct vision and within the protection of
      saline solution, epidural scarring, extruded and sequestrated disc protrusions
      and/or osteophytes are removed by holmium laser ablation. The patient is
      responsive and aware under neurolept analgesia and this ensures the protection
      and the integrity of the nerve root. A total of 219 such interventions has been
      performed up to January 1, 1997. The first 48 cases with a follow-up exceeding 12
      months have been included in this preliminary review. Initial experience is
      encouraging. The ELF seems to provide another means of addressing sequelae of
      primary degenerative disorders as well as the common consequences of conventional
      spine surgery. ELF provides an alternative to minimal intervention fenestrectomy
      and open surgical undercutting for predominantly unisegmental and unilateral
      lateral recess stenosis and in selected cases it may prevent or delay the
      indication of spinal fusion.

PMID- 9565958
TI  - The use of small malleable endoscopes to assess pedicle screw placement:
      technical note.
AB  - Because the improper insertion of pedicle screws can be associated with
      significant neurologic morbidity, attempts are being made to improve on the
      accuracy of pedicle screw placement. As a possible strategy we have studied the
      use of small malleable endoscopes to explore the pedicle and exiting nerve root
      during and after pedicle screw placement. These small endoscopes are 1.2 mm in
      diameter and can be bent so that the superior, medial and inferior walls of the
      pedicle can be visualized. Additionally, the nerve roots superior to and inferior
      to the pedicle can be seen throughout their entire intraspinal course. Using
      these endoscopes in ten patients requiring the placement of forty-four pedicle
      screws we were able to visualize the pedicles and nerve roots in all cases. The
      endoscope demonstrated that one screw had penetrated the inferior cortex of the
      pedicle. This penetration was not palpable with blind probing of the pedicle and
      foramina. These cases suggest that this simple technique may be of use in
      limiting improper pedicle screw placement.

PMID- 9565959
TI  - Intraoperative three-dimensional ultrasonography: an approach to register brain
      shift using multidimensional image processing.
AB  - Neuronavigation uses the skull as a reference system for transfer of image-space
      data to physical space during brain surgery. This requires a stable spatial
      relation between the skull and intracranial structures. However, especially dura
      opening and preparation for lesion removal causes brain shift. This shift may
      mislead the surgeon unless preoperatively defined image-space data are corrected
      for shifting online intraoperatively. Since a real-time modality is required
      intraoperatively, we propose three-dimensional (3 D) ultrasonography for
      detection of brain shift. By coupling common ultrasound probes (3.5/6.5 MHz) to a
      magnetic digitizer receiver 2 D-ultrasound scans were obtained intraoperatively
      along with their spatial orientation. 3 D-ultrasonography was achieved by
      alignment of sequentially obtained 2 D-scans. For multimodal matching,
      preoperative MRI data was segmented for landmarks (cerebral ventricles, lesion)
      automatically. The 3 D-ultrasonography data set scanned intraoperatively was
      contoured and matched with the MRI data set. Intraoperative 3 D-ultrasonography
      revealed excellent delineation of landmarks in almost real time in six patients
      studied. Matching of MRI data and intraoperative 3 D-ultrasonography data was
      successful with good correspondence of landmarks. Intraoperative 3 D
      ultrasonography is proposed as a promising tool for on-line detection of brain
      shift during intracranial operations.

PMID- 9565960
TI  - Microanatomical considerations for the fenestration of the septum pellucidum.
AB  - The anatomical foundations for the endoscopic fenestration of the septum
      pellucidum have not been presented previously in an isolated fashion. Using a
      surgical microscope, the microsurgical anatomy of the septum pellucidum, lateral
      ventricles, and surrounding structures was examined in ten adult brains injected
      with silicone rubber. The mean anteroposterior length of the septum pellucidum
      was 41 mm (range 40-42). Its mean height was 13.11 mm (range 12-15) at the level
      of the foramen of Monro; 10 mm (range 9-11) at the frontal horns, and 8 mm (range
      7-10) at the ventricular atrium. One to three septal veins delimited 2 or 3
      avascular areas in the septum pellucidum. We found an anterior area which was
      consistently avascular and large enough to be fenestrated safety. More posterior
      areas, while avascular, were inconsistent in their size and shape.

PMID- 9565961
TI  - Interactive image guided surgery of the pineal region.
AB  - A wide variety of lesions occur in the pineal region. Of these, only 25% may
      benefit from surgical resection, being benign or radioresistant in nature. In the
      remaining 75% (malignant or radiosensitive), a conservative approach is
      preferred. Surgical resection of lesions arising from the pineal region has been
      associated with high morbidity and mortality, due to the complex microanatomy of
      this area. Recently computer-assisted surgery has emerged as an ideal method to
      safely approach many intracranial lesions. In the present study we discuss our
      experience in interactive image-guided surgical management of pineal mass
      lesions, in terms of patient selection, methodology, and surgical morbidity and
      mortality. From July 1992 to December 1996, 15 patients underwent interactive
      image guided surgical procedures. There were eight men and seven women. Age
      ranged from 5 to 79 years (mean 30). Preoperatively all patients underwent
      neuroimaging studies that included computed tomography and magnetic resonance
      imaging under stereotactic conditions. Surgical planning was carried out using
      the Neurological Surgical Planning System software developed at Wayne State
      University. In patients with a preoperative diagnosis of a malignant or
      radiosensitive lesion (n = 10), an interactive image-guided stereotactic biopsy
      was considered, whereas for those with benign or radioresistant lesions (n = 5)
      surgical excision using an infrared based system was carried out. Histological
      diagnosis was obtained in all patients. There was no morbidity and mortality
      associated with computer-assisted procedures for biopsies the diagnostic yield
      was 100%. For patients that underwent interactive image-guided surgery, gross
      total removal was accomplished in 3 and in 1 patient a subtotal resection greater
      than 90% was achieved. Interactive image-guided biopsy represents a safe and
      accurate method in the diagnosis of malignant and/or radiosensitive pineal
      lesions. Using this technique surgeons can simulate preoperatively the surgical
      trajectory, thus avoiding damage to critical and vascular structures. For
      patients with benign or radioresistant lesions, computer-assisted surgical
      excision is recommended.

PMID- 9565962
TI  - Interactive image-guided neuroendoscopy: development and early clinical
      experience.
AB  - Technical advances and pioneering surgeons have established neuroendoscopy as an
      accepted diagnostic and therapeutic tool. The clinical indications for endoscopy,
      variety of operative techniques and number of endoscopic surgeons continue to
      increase steadily. However, there are fundamental limits to the scope of freehand
      endoscopy principally governed by the need for direct vision of anatomical and
      pathological structures. In addition, whilst the expert neuroendoscopist is only
      occasionally disorientated by complex distorted anatomy, the rising number of
      novices are likely to be mislead relatively often. We report the integration of
      neuroendoscopy with an optical neuronavigation system to provide interactive
      image-guided neuroendoscopy. This combination both removes the constraining
      requirement for direct vision and provides accurate localisation to guide the
      surgeon during surgery. We describe the clinical application of this method to
      two cases where image-guided endoscopy was essential to the safe completion of
      the procedure.

PMID- 9565963
TI  - Primary multiple cerebral hydatid cysts: case report with CT and MRI study.
AB  - We present a case of a patient with multiple cerebral hydatidosis. We could not
      find any other origin of hydatidosis. In the light of the radiodiagnostic and
      biochemical findings, we assessed this case as a primary cerebral hydatidosis.
      The cysts were delivered completely. Two months after operation, the patient's
      neurological examination and control MRI were normal.

PMID- 9565964
TI  - Minimally invasive treatment of giant CSF pseudocyst complicating
      ventriculoperitoneal shunt.
AB  - A two-liter cerebrospinal fluid pseudocyst complicating a ventriculoperitoneal
      shunt was drained and a distal catheter retrieved from the peritoneal cavity by
      laparoscopy. Adoption of such a minimally invasive approach allowed the prompt
      resolution of the complication and an early recovery for out patient.

PMID- 9565965
TI  - Delayed cyst formation after radiosurgery for cerebral arteriovenous
      malformation: two case reports.
AB  - Two patients who underwent gamma knife radiosurgery for ruptured cerebral
      arteriovenous malformations (AVM) developed cystic lesions at 78 and 111 months
      after undergoing treatment. Both patients presented initially with intracerebral
      hemorrhage. In one patient, the cystic lesion was discovered during routine
      follow-up imaging and clinical examination revealed homonymous hemianopsia; the
      second patient presented with seizure and the lesion was identified more than 9
      years after radiosurgery. One patient underwent resection of the nidus and
      histologic analysis of the resected specimen showed vessels in various stages of
      obliteration. The present paper discusses the possible mechanism for the delayed
      development of cystic lesions, and the possibility that radiation-induced
      vascular changes may continue in a nidus even when angiography shows complete
      obliteration of the nidus.

PMID- 9565966
TI  - Traumatic basilar artery dissection causing locked-in syndrome.
AB  - We report on a patient with traumatic dissection limited to the basilar artery
      causing a locked-in syndrome. Magnetic resonance imaging (MRI) showed infarction
      of the basis pontis and a high signal intensity ring surrounding the central
      lumen of the basilar artery. Vertebral angiography revealed a double lumen within
      the basilar artery, consistent with a dissection. MRI and angiography are
      complementary to each other, and we consider both to be necessary for accurate
      diagnosis. Because MRI is less invasive than angiography, MR examinations should
      be performed before angiography for screening.

PMID- 9565967
TI  - L-DOPA exacerbates amphetamine-induced dopamine depletion.
AB  - Administration of L-DOPA to Parkinson patients has been suggested to exacerbate
      "functional denervation" of the nigrostriatal system. Therefore, experiments were
      conducted to determine if L-DOPA combined with the DOPA decarboxylase inhibitor,
      Ro4-4602 (benserazide hydrochloride) would potentiate amphetamine-induced
      neurotoxicity. Mice received two injections of saline or benserazide + L-DOPA
      (25.0 or 100.0 mg/kg) interspersed with four injections of amphetamine (15.0
      mg/kg) at 2-h intervals. Significant depletion of striatal dopamine, DOPAC, and
      HVA was evident 1 wk following amphetamine administered with or without 25.0
      mg/kg L-DOPA + benserazide, whereas 100.0 mg/kg L-DOPA + benserazide potentiated
      amphetamine-induced depletion of striatal dopamine (17 vs 28% of control values).
      This enhanced toxicity may be consequent to increased dopamine turnover following
      L-DOPA (360 vs 231%), a situation akin to that observed in compromised
      dopaminergic nigrostriatal systems of parkinsonian patients. Furthermore,
      striatal 5-HT was not altered by amphetamine alone, whereas concurrent
      administration of L-DOPA/ benserazide depleted 5-HT to 82% of control values. No
      changes were evident in the frontal cortex following amphetamine with or without
      concurrent L-DOPA/benserazide; however, L-DOPA/benserazide administered alone
      reduced 5-HT and 5-HT turnover to 58% of control values.

PMID- 9565969
TI  - Anoxic injury of endothelial cells causes divergent changes in protein kinase C
      and protein kinase A signaling pathways.
AB  - Alterations in protein kinase C (PKC) and cAMP-dependent kinase have been
      documented in anoxic brain injury. However, the regulation of these signaling
      enzymes in the cerebrovasculature has not been explored. In this study, cultured
      brain endothelial cells exposed to anoxic injury (anoxia--20 min/reoxygenation-
      40 min) showed both a significant increase (p < 0.001) in PKC and decrease (p <
      0.01) in cAMP-dependent kinase activity. Analysis of PKC by Western blot
      indicated an increase in kinase level in response to anoxic injury, whereas there
      was no change in the level of cAMP-dependent protein kinase, as measured by
      labeled cAMP binding. Inhibition of nitric oxide synthase did not affect these
      changes. Addition of the nitric oxide-releasing compound sodium nitroprusside
      caused a dose-dependent increase in the activity of both signaling systems in
      endothelial cells. These data demonstrate that anoxic injury of brain endothelial
      cells in culture causes significant and divergent changes in signaling kinase
      activity. Abnormalities in brain endothelial PKC and cAMP-dependent kinase could
      have important consequences for the blood-brain barrier in anoxic brain injury.

PMID- 9565968
TI  - Prenatal ethanol exposure enhances glutamate release stimulated by quisqualate in
      rat cerebellar granule cell cultures.
AB  - Effects of prenatal ethanol exposure on extracellular glutamate accumulation
      stimulated by glutamate receptor agonists were studied in rat cerebellar granule
      cell cultures. The prenatal exposure to ethanol was achieved via maternal
      consumption of a Sustacal liquid diet containing either 5% ethanol or isocaloric
      sucrose (pair-fed) substituted for ethanol from gestation d 11 until the day of
      parturition. Neither the basal level of extracellular glutamate nor the increased
      accumulation of glutamate stimulated by KCl (40 mM) or by ionotropic glutamate
      receptor agonists, N-methyl-D-aspartate (NMDA) or kainate (KA) (100 microM each),
      in cells prepared from the ethanol-fed group was significantly different from
      that in cells prepared from the pair-fed group. Glutamate accumulation stimulated
      by quisqualate (QA, 100 microM) or by trans-(+/-)-1-amino-1,3
      cyclopentanedicarboxylic acid (t-ACPD, 250 microM) in the ethanol-fed group was
      higher than that in the pair-fed group by 116 and 36%, respectively. In the
      presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 100 microM), an
      ionotropic QA receptor antagonist, the QA-induced accumulation of glutamate in
      the ethanol-fed group was still higher than that in the pair-fed group. In the
      presence of MK-801 (5 microM), an antagonist of the NMDA receptor, the enhanced
      accumulation of glutamate stimulated by either QA or t-ACPD was still observable
      in the ethanol-fed group as compared to the pair-fed group. Addition of (RS)
      alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM), a selective antagonist of
      the metabotropic glutamate receptor, abolished the enhanced accumulation of
      glutamate stimulated by either QA or t-ACPD in the ethanol-fed group. Although
      immunoblotting of mGluR1 and mGluR2/3 did not show apparent differences between
      the pair-fed and the ethanol-fed groups, the overall results suggest that the
      effect of prenatal ethanol exposure was selectively through a pathway mediated by
      the metabotropic glutamate receptor.

PMID- 9565970
TI  - Interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor type I, IL-1 receptor
      antagonist, and TGF-beta 1 mRNAs in pediatric astrocytomas, ependymomas, and
      primitive neuroectodermal tumors.
AB  - Interleukin-1 alpha (IL-1 alpha), IL-1 beta, interleukin-1 receptor type I (IL
      1RI, signaling receptor), and IL-1 receptor antagonist (IL-1Ra, endogenous
      inhibitor) are pivotal components of the IL-1 system. IL-1 and other cytokines
      induced by IL-1, such as TGF-beta 1, may participate in the growth of various
      tumor cells. In children, primary nervous system tumors represent the most common
      solid malignancy. We investigated the levels of IL-1 alpha, IL-1 beta, IL-1RI, IL
      1Ra, and TGF-beta 1 mRNAs in pediatric astrocytomas (n = 19), ependymomas (n =
      13), and primitive neuroectodermal tumors (n = 22) using sensitive and specific
      RNase protection assays. The data show a significant distinct cytokine mRNA
      profile among brain tumor types. Pilocytic, nonpilocytic, and anaplastic
      astrocytomas have significant increased levels of IL-1 beta, IL-1RI, and TGF-beta
      1 mRNAs, but low levels of IL-1Ra mRNA; this may have implications for an IL-1
      beta feedback system and IL-1 beta<-->TGF-beta 1 interactions in astrocytomas.
      Ependymomas show increased levels of IL-1 alpha and IL-1 beta mRNAs associated
      with low levels of IL-1Ra mRNA; primitive neuroectodermal tumors do not exhibit
      increased levels of any cytokine component examined. The data also suggest that a
      dysregulation of the balance between stimulatory and inhibitory cytokines may be
      involved in the growth and development of brain tumors via autocrine/paracrine
      mechanisms.

PMID- 9565971
TI  - Oxidized lipoproteins may play a role in neuronal cell death in Alzheimer
      disease.
AB  - Oxidative stress in the central nervous system (CNS) may cause oxidation of
      lipoprotein particles. The oxidized lipoproteins may damage cellular and
      subcellular membranes, leading to tissue injury and cell death. Human low-density
      lipoprotein (LDL) and very low-density lipoprotein (VLDL) are oxidized by
      transition metal ions, such as Cu2+. Using PC 12 cells, we tested the
      cytotoxicity of oxidized LDL and VLDL. Cell death was increased in a dose
      dependent manner. Antioxidants added to the incubation medium, such as vitamins E
      or C, or resveratrol showed some protection. Results indicated that oxidized
      lipoproteins may serve as an oxidative stressor, which may initiate the neuronal
      cell death leading to the manifestation of Alzheimer disease (AD).

PMID- 9565972
TI  - [Thyroid gland function in lithium treatment].
AB  - Lithium is widely used in the acute and prophylactic treatment of affective
      disorders. Lithium affects thyroid hormone metabolism via different mechanisms.
      In patients this leads to a compensatory increase in pituitary thyroid
      stimulating hormone (TSH) which usually maintains the euthyroid status. This is
      probably the reason for the relatively high prevalence of goitre in lithium
      treated patients; however, the enlargement of the gland is only moderate in most
      cases. Due to its immunostimulating effects lithium may support the appearance of
      thyroid auto-antibodies and the development of thyroiditis, which may be the
      reason for a higher prevalence of hypothyroidism in patients receiving lithium.
      However, also cases of hyperthyroidism in such patients have been reported
      repeatedly. Therapeutic recommendations for the treatment of disturbances of
      thyroid function during lithium treatment are given.

PMID- 9565973
TI  - [Schizophrenia concepts in Soviet and Russian psychiatry].
AB  - Concepts of schizophrenia of the Soviet Russian school are presented. They are
      historically based upon the broad concepts of schizophrenia by Kraepelin and
      Bleuler. The relationships to the German concept of "Einheitspsychose" (unitary
      psychosis) is emphasized. Along with the discussion of correspondence to and
      differences with Western diagnostic systems (DSM, ICD) it is pointed out that the
      old Soviet system of classification extends to psychotic and also non-psychotic
      forms which in ICD-10 are not attributed to schizophrenia, but to other
      categories. Differential-diagnostic criteria of sluggish schizophrenia and
      neurosis, such as positive psychopathological symptoms, thought disturbances and
      changes in personality, will be delineated. Furthermore, recent developments in
      Russian psychiatry and modifications in Russian schizophrenia concepts will be
      exemplified by the concept of "psychic diathesis."

PMID- 9565974
TI  - [The social status of schizophrenic patients].
AB  - In the German multicenter ANI study comparing continuous prophylactic treatment
      with intermittent medication, the social situation of a large sample of 364
      schizophrenic patients was investigated and followed up over a 2-year period of
      outpatient aftercare. Effective therapy and prophylaxis substantially reduced
      relapses and rehospitalization. On the other hand, the psychosocial situation
      still showed considerable disadvantages. Of the patients (35 years old on
      average), 60% were still unmarried. Almost one-half of the patients still lived
      alone or with their parents, and one-third lived a very solitary life. At the end
      of the 2-year aftercare period, one-third was able to earn their own living.
      Almost one-half retired early from their occupations. Predictors and intervening
      variables are presented in order to stimulate early rehabilitation approaches.
      Schizophrenics are particularly placed at a disadvantage by tighter competition
      in the employment market, even though the course of illness can be improve.
      Social psychiatry must to be involved in helping to improve social contacts,
      accommodation and employment in order to prevent major distress.

PMID- 9565975
TI  - [The course of illness and rehabilitation of schizophrenic patients in ambulatory
      vocational therapy. A prospective study over 3 years].
AB  - Within the framework of a study on vocational rehabilitation of the mentally ill,
      we examined 83 schizophrenic outpatients enrolled in a work therapy program. The
      course of illness and rehabilitation was documented over a 3-year period by means
      of annual follow-up examinations. The sample comprised 44 men and 39 women with
      an average age of 35 years (SD +/- 8.5). The majority were chronically ill
      patients with a history of frequent and long psychiatric hospitalization. After 3
      years, 22% of the patients were integrated into the general labor market, 26% had
      sheltered employment, 23% were still in work therapy, and 29% were unemployed.
      Besides the patients' subjective expectations, early introduction of
      rehabilitative measures and a favourable course of illness were found to be
      predictors of a successful rehabilitation leading to vocational integration.
      Outpatient work therapy is a contemporary, effective organizational form of
      sociotherapy. It may contribute to improved vocational competence and
      integration, reduced psychiatric hospitalization and stabilized psychopathology.

PMID- 9565976
TI  - [Measuring changes in subjective quality of life in chronic schizophrenic
      patients].
AB  - Subjective quality of life in a group of chronic schizophrenia outpatients was
      assessed within 1 1/2 years (n = 50) and 4-6 weeks (n = 47) using the Berliner
      Lebensqualitatsprofil (German version of the Lancashire Quality of Life Profile).
      There had been no systematic therapeutic interventions meanwhile. Stability and
      constancy for the longer interval was similar to results in the general
      population. The statistics for the shorter interval justify in particular use of
      the profile's total score and general well-being for the measurement of change.
      In contrast to cross-sectional data and the longer observation period, no
      significant common variation between psychopathological symptoms and subjective
      quality of life could be found for the shorter period.

PMID- 9565977
TI  - [Phenomenology of cycloid axis syndromes and their delineation from a
      schizophrenic core group].
AB  - The concept of cycloid psychoses means a certain species as part of the group of
      schizophrenias. From our clinical point of view, the subtypes of Leonard and
      their poles are axial syndromes. They can occur simultaneously or intermingle
      during one phase. In the present phenomenological study the inner connections of
      these axial syndromes are shown. Apart from these connections, cycloid psychoses
      can be differentiated from core schizophrenia by three conditions: (1) the lack
      of deformation of affect and affect expression; (2) the lack of deformaton of
      thought structure; and (3) the lack of certain movement deformations, e.g.,
      parakinesis. Our concept of phenomenon is explained to criticize the current
      operational definitions of cycloid psychoses. A different approach is suggested.

PMID- 9565978
TI  - [The 5 factor model of childhood schizophrenia].
AB  - Forty-four first-admission patients with childhood-onset schizophrenia (age at
      onset < or = 14 years) were examined retrospectively for 30 clinical symptoms
      using the Positive and Negative Syndrome Scale (PANSS; 15). A principal component
      analysis with varimax rotation was applied to the full item set of this scale and
      revealed five orthogonal independent symptom groups: cognition affect, social
      withdrawal, anti-social behavior, excitement, and reality distortion. In order to
      validate these psychopathological dimensions we analyzed the relation between the
      five factor scores and outcome variables (Disability Assessment Schedule, DAS-M;
      13) several years after onset: Social withdrawal was correlated with poor
      outcome; reality distortion was related to good outcome (P < 0.01). A
      multivariate ANOVA identified group differences in the anti-social behavior
      factor between acute and insidious onset of illness and between boys and girls;
      patients with an acute onset scored significantly higher on the excitement factor
      than those with an insidious onset (P < 0.05). According to our results more than
      two dimensions are necessary to describe the psychopathology of childhood-onset
      schizophrenia, similar to adolescent- and adult-onset schizophrenia.

PMID- 9565979
TI  - [Dimensions of schizophrenia in the elderly. Correlations with cognitive and
      motor symptoms].
AB  - In most factor analytical studies of schizophrenic symptomatology a three-factor
      solution was found. The aim of this study was to investigate symptomatological
      dimensions in old age and to clarify whether the dimensions correlate differently
      with neuropsychological and motor parameters. A total of 131 DSM-III-R
      schizophrenics (mean age 68 years) were assessed using SANS, SAPS, a
      neuropsychological test battery and motor scales. A factor analysis yielded three
      dimensions (negative, disorganized, paranoid), two of which (negative,
      disorganized) showed different correlations with neuropsychological and motor
      phenomena. Thus, three symptomatological dimensions could also be demonstrated in
      a chronic, old-age schizophrenic sample. The pathophysiological significance of
      the different correlations with neuropsychological and motor parameters should be
      clarified in neuroimaging and neuropathological studies.

PMID- 9565980
TI  - [Sex specific differences in hemispheric lateralization in schizophrenia? An MEG
      MRI study].
AB  - In this magnetoencephalography study the issue of hemispheric lateralisation in
      patients with schizophrenia was addressed using acoustically evoked neuromagnetic
      fields. The characteristics of dipoles in the superior temporal gyrus, the
      primary auditory cortex, were calculated. In contrast to other studies,
      alterations did not concern the localisation, but rather the orientation of
      dipoles. Of pathophysiological interest was that the dipoles abnormalities were
      found left-hemispherically in male (p = 0.02) and right-hemispherically in female
      patients with schizophrenia (p = 0.01) when compared to controls. The findings
      suggest gender-specific alterations of hemispheric lateralisation in
      schizophrenia.

PMID- 9565981
TI  - [Cataphasia: a by formal thought disorders and speech characteristics
      distinguished psychosis of the schizophrenic domain].
AB  - Cataphasia, one form of Leonard's unsystematic schizophrenias, shows a
      polymorphous, but nevertheless specific symptomatology. The key features of the
      psychopathology of this condition are formal thought and speech disorders.
      Hallucinations and delusional ideas can be present, but they are incidental and
      do not determine the syndrome. The characteristic elements of this thought
      disorder are logical derailment, paralogic thinking and, especially in the
      excited form, incoherence with contaminations up to "word salad". The speech
      shows strange verbalizations, paragrammatisms, agrammatisms, and occasionally
      neologisms. The course mostly fluctuates with acute attacks and incomplete
      remissions leading to residual states of varying degrees of severity determined
      by a flattened and somewhat euphoric affect. Usually the disorder appears in an
      excited or inhibited form. In the latter case, thought disorder is difficult to
      recognize. Sometimes it can only be stated by the facial expression, which
      reveals an internal emptiness and dullness, and a tendency to state fixedly at
      the examiner. Psychopharmacotherapy can diminish accompanying delusional ideas or
      hallucinations, but does not have much influences on the core syndrome of formal
      thought and speech disorder.

PMID- 9565982
TI  - [Schizophrenia-like symptoms in the Westphal-Strumpell variation of Wilson
      disease].
AB  - Wilson's disease is a rare, autosomal recessive disorder of copper metabolism due
      to low serum ceruloplasm, resulting in increased copper deposition, especially in
      the liver and basal ganglia in the brain. The pseudosclerotic type of Wilson's
      disease, also known as the Westphal-Strumpell form, is distinguished by
      positional tremor, ataxia and dysarthria as the main symptoms. We use the example
      of a 23-year-old patient whose neurological symptoms were preceded by a long
      history of a schizophrenic-like disorder. Clinical symptoms are presented. MRI,
      SPECT and PET images are illustrated. Therapy and outcome are discussed.

PMID- 9565983
TI  - ["BPSSD": behavioral disorders in dementia. A new diagnostic and therapeutic
      concept?].

PMID- 9565984
TI  - Very-long-chain acyl-coenzyme A dehydrogenase deficiency in a child with
      recurrent myoglobinuria.
AB  - A 9-year-old boy had recurrent episodes of myoglobinuria and normal urinary
      organic acid profile. Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD)
      deficiency was detected biochemically in cultured skin fibroblasts and confirmed
      by Western blot analysis. The patient had a distinctive plasma fatty-acid
      profile, which was present even between attacks. Early diagnosis of this disorder
      is important because of the apparently protective effect of an appropriate
      dietary regimen.

PMID- 9565985
TI  - Neurotrophic factors decrease the release of creatine kinase and prostaglandin E2
      from metabolically stressed muscle.
AB  - We have used an in vitro model of oxidative stress by exposing rat muscle to 2:4
      dinitrophenol. This causes an efflux of creatine kinase (CK) and prostaglandin E2
      (PGE2) commonly used as indicators of muscle cell damage. We then investigated
      compounds with a putative cell protective effect in the system. Ciliary
      neurotrophic factor, brain derived neurotrophic factor and insulin like growth
      factor 1 all prevent the release of PGE2 and CK. To the extent that these
      indicators may reflect cell damage, the results might support the investigation
      of the therapeutic potential of these compounds in muscle disease.

PMID- 9565986
TI  - Muscle cells from mdx mice have an increased susceptibility to oxidative stress.
AB  - Several lines of evidence suggest that free radical mediated injury and oxidative
      stress may lead to muscle necrosis in the muscular dystrophies, including those
      related to defects in the dystrophin gene. We have examined muscle cell death
      using an in vitro assay in which the processes that lead to myofiber necrosis in
      vivo may be amenable to investigation in a simplified cell culture system. Using
      myotube cultures from normal and dystrophin-deficient (mdx) mice, we have
      examined the susceptibilities of the cells to different metabolic stresses.
      Dystrophin-deficient cells were more susceptible to free radical induced injury
      when compared to normal cells, but the two populations were equally susceptible
      to other forms of metabolic stress. The differential response appeared to be
      specifically related to dystrophin expression since undifferentiated myoblasts
      (which do not express dystrophin) from normal and mdx mice were equally sensitive
      to oxidative stress. Thus, the absence of dystrophin appears to render muscle
      specifically more susceptible to free radical induced injury. These results
      support the hypothesis that oxidative stress may lead to myofiber necrosis in
      these disorders. Elucidating the mechanisms leading to cell death may help to
      explain the variabilities in disease expression that are seen as a function of
      age, among different muscles, and across species in animals with muscular
      dystrophy due to dystrophin deficiency.

PMID- 9565987
TI  - Sparing of mdx extraocular muscles from dystrophic pathology is not attributable
      to normalized concentration or distribution of neuronal nitric oxide synthase.
AB  - Previous findings have led to speculations that decreased concentration of nNOS
      (neuronal nitric oxide synthase) may underlie some aspects of the pathophysiology
      of dystrophic muscle. We have tested whether the sparing of extraocular muscles
      (EOM) in muscular dystrophy is attributable to the presence of normal nNOS
      concentration and distribution in these muscles. Measurements of total nNOS
      concentration in control muscle showed that total nNOS comprises approximately
      0.05% of total muscle protein, indicating a molar stoichiometry of approximately
      60 and 20 to total dystrophin and syntrophin, respectively. Thus, most muscle
      nNOS is either not associated with the dystrophin complex, or binds to yet
      unidentified sites in the complex. nNOS concentration was at least two-fold
      greater in C57 EOM and tibialis anterior (TA) compared with mdx samples. No
      significant differences in nNOS concentration in EOM versus TA in either mdx or
      C57 mice were observed, nNOS was concentrated at the sarcolemma of all C57
      samples, while mdx nNOS displayed a cytosolic distribution, except in fibers that
      reverted to express dystrophin. These data show that mdx EOM are spared by a
      mechanism other than normalized concentration and location of nNOS.

PMID- 9565988
TI  - Beta-sarcoglycan: genomic analysis and identification of a novel missense
      mutation in the LGMD2E Amish isolate.
AB  - The sarcoglycan complex is involved in the etiology of four autosomal recessive
      limb-girdle muscular dystrophies (LGMD2C-F). A missense mutation (T151R) in the
      beta-sarcoglycan gene on chromosome 4q12 has been shown to cause a mild form of
      LGMD2E in 11 families from a Southern Indiana Amish community sharing a common
      haplotype. We now report that two sibs from another Amish family with mild LGMD2E
      are compound heterozygotes for chromosome 4q12 markers. In order to characterize
      the genetic defect in this new family, we determined the genomic organization of
      the beta-sarcoglycan gene. A second missense mutation (R91C) has now been
      identified in this LGMD2E Amish family. This mutation is also present in the
      homozygous state in another family of probable Amish ancestry. Finally, analysis
      of all the components of the dystrophin-glycoprotein complex was performed for
      the first time on a biopsy from a patient homozygous for the beta-sarcoglycan
      mutation (T151R). Interestingly, in addition to the loss of the entire
      sarcoglycan complex, we detected a reduction of alpha-dystroglycan which suggests
      a role for the sarcoglycan complex in stabilizing alpha-dystroglycan at the
      sarcolemma.

PMID- 9565989
TI  - Impaired cerebral glucose metabolism in myotonic dystrophy: a triplet-size
      dependent phenomenon.
AB  - Myotonic dystrophy (DM) is caused by an expansion of a CTG triplet repeat
      sequence in the 3'-noncoding region of a protein kinase gene, yet the mechanism
      by which the triplet repeat expansion causes disease remains unknown. Impaired
      glucose penetration into brain tissues has been described in DM patients and is a
      phenomenon that remains unexplained. The present study shows that altered brain
      glucose metabolism is triplet repeat dependent. We studied brain glucose
      metabolism (CMRGlu, mumol/100 g/min) by the use of positron emission tomography
      and 18F-fluoro-2-deoxy-D-glucose in 11 ambulatory non-obese DM patients and in 11
      age and sex matched healthy subjects. All subjects underwent a glucose tolerance
      test with plasma insulin determinations. The expansion of CTG triplet repeats was
      analyzed in patients with the probe cDNA25 after EcoRI digestion. As compared to
      controls, in DM patients, the CMRGlu was significantly decreased (26.26 +/- 5.05
      vs. 33.43 +/- 2.18, mumol/100 g/min, P = 0.004), and after oral glucose loading,
      plasma insulin levels were significantly higher and plasma glucose levels
      remained unchanged (respectively, F = 11.21, P = 0.004 and F = 0.20, P = 0.66).
      Subsequently, the glucose/insulin ratio was significantly lower in DM patients (F
      = 6.25, P = 0.02). The length of the expansion of the CTG repeats correlated
      negatively with the CMRGlu (r2 = 0.63, P = 0.003) and positively with the area
      under the curve for insulin changes over time after oral glucose (r2 = 0.49, P =
      0.016). We conclude that, in DM patients, the brain metabolism of glucose is
      impaired in a repeat dependent manner.

PMID- 9565990
TI  - Platelet function deficiency in Duchenne muscular dystrophy.
AB  - Platelet function and plasmatic coagulation of 51 patients with Duchenne muscular
      dystrophy (DMD) were studied in order to find an explanation for the known
      substantial blood loss in spinal surgery of these very patients. A normal
      plasmatic coagulation and a slight but not significant increase of bleeding time
      was found. However, a significant deficiency of platelet adhesion and ristocetin
      induced aggregation (P < 0.001) as well as a marked reduction of expression of
      glycoprotein i.v. (synonyms: GPIV, GPIIIb, CD36) to 50% were detected. We
      conclude from our study, that this finding of deficiency of platelet function in
      DMD patients is of no importance in everyday life and minor operations, e.g.
      lower limb surgery. In major spinal surgery, however, the platelet function
      deficiency occurs. A decompensation of platelet adhesion as well as aggregation
      capacity can be assumed due to the unavoidable intraoperative dilution effect by
      the inevitable volume replacement.

PMID- 9565992
TI  - 51st ENMC International Workshop: Nemaline Myopathy. 13-15 June 1997, Naarden,
      The Netherlands.

PMID- 9565991
TI  - Guillain-Barre syndrome with associated thrombocytopenia: prompt response to
      combined corticosteroid and immunoglobulin treatment.
AB  - We report a case of Guillain-Barre syndrome (GBS), requiring prolonged mechanical
      ventilation, associated at its presentation with thrombocytopenia, in a 50-year
      old woman. She was treated with immunoglobulin, and short-term corticosteroids
      for thrombocytopenia. In spite of the severe presentation we observed a very good
      and rapid recovery, which could have been determined by the therapeutic
      association. The incidence of thrombocytopenia in GBS patients could be
      underestimated, and should be kept in mind in order to avoid hemorrhagic
      complications.

PMID- 9565993
TI  - 52nd ENMC International Workshop: International Consortium on Nucleo
      mitochondrial Interactions. 4-6 July 1997, Naarden, The Netherlands.

PMID- 9565994
TI  - Neuromuscular disorders: gene location.

PMID- 9565995
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 9565996
TI  - [Neural regeneration and its promoting factors in peripheral nerves].

PMID- 9565997
TI  - [Optic nerve regeneration and functional recovery of vision following peripheral
      nerve transplant].

PMID- 9565998
TI  - [Cytology of posttraumatic nerve repair of the spinal cord].

PMID- 9565999
TI  - [Functional difference between the left supplementary motor area and the left
      premotor area in a task of confrontation naming and word fluency].
AB  - We assessed the faculty of confrontation naming and word fluency of the 11
      patients afflicted with frontal lobe infarction or hemorrhage. All the patients
      were right-handed and manifested transcortical motor aphasia due to
      cerebrovascular diseases. We carried out the Western Aphasia Battery, and we
      adopted V-A; the naming task involved confrontation naming of 20 objects, and V
      B; the word fluency task involved the naming as many animals as possible in a one
      minute period. Six patients who have lesions in the left medial frontal lobe
      performed excellency in the confrontation naming task but exhibited poor word
      fluency, and 5 patients who have lesions in the left dorso-lateral frontal lobe
      performed poorly in both tasks. This results suggests that the left dorso-lateral
      frontal lobe is important in confrontation naming, while the left medial frontal
      lobe is important in word fluency. Mushiake et al. (1991) showed that the
      premotor area was involved in visually guided sequential movements, and the
      supplementary motor area was involved internally determined sequential movements
      in primates. Regarding language function as analogous to movement, confrontation
      naming is analogous to visually guided movements and word fluency is analogous to
      internally determined movements. Thus, our results suggest that the functional
      difference between the left medial frontal lobe, which includes the supplementary
      motor area, and the left dorso-lateral frontal lobe, which includes the premotor
      area, which was demonstrated in primates for movement is also true of language
      function in humans.

PMID- 9566000
TI  - [Improvement of cognition after trepanation for the chronic subdural hematoma].
AB  - The cognitive functions were examined in the pre- and post-operative stages about
      the 16 cases of the chronic subdural hematoma. The evaluation was performed with
      MMS (mini-mental state) test. Although the average of the total score was 16.6 in
      the preoperative stage, it increased to 22.7 in the postoperative stage.
      Orientation of time and place, recall and the ability of writing a sentence,
      which were impaired prominently in the preoperative stage, improved significantly
      in the postoperative stage. The improvement was poorer in the patients with gait
      instability and in those older than 80 years. Trepanation surgery seems to be
      efficient for the improvement of cognition.

PMID- 9566002
TI  - [Radical endovascular surgery of a huge cavernous internal carotid artery
      aneurysm of an aged patient].
AB  - A case of a huge aneurysm of the cavernous portion of the internal carotid artery
      (ICA) is reported. The aneurysm was successfully treated by endovascular surgery.
      A 78-year-old woman presenting with mild headache and cavernous sinus syndrome on
      the left side was incidentally disclosed to have a huge aneurysm at the cavernous
      portion of the left ICA by MRI and MRA. An angiogram revealed that the aneurysm
      had a broad neck. In view of patient's age, concomitant coronary ischemia and
      wide aneurysmal neck, endovascular surgery under local anesthesia was thought to
      be the treatment of choice. The aneurysmal sac was completely embolized with
      platinum coils and the ICA by a balloon proximal to the aneurysm. Over the 5
      months period, the patient's symptoms has all disappeared save for mild abducens
      palsy. It is believed that neck clipping is the method of treatment of
      intracranial aneurysms. However, endovascular surgery is less invasive and may be
      applicable to some of high risk patients.

PMID- 9566001
TI  - [Relationship between imaging and pathological features and clinical factors in
      surgical cases of temporal lobe epilepsy].
AB  - The relationships between imaging, pathology and presumed causes in surgical
      cases of temporal lobe epilepsy (TLE) was studied. The subject was 62 patients
      (33 males and 29 females) who had had no attacks for more than one year after
      surgery. Average age at surgery was 28.2 +/- 9.9 years. Obvious neurological
      abnormalities were not found in these cases. MRI, PET and SPECT were performed.
      Hematoxylin and eosin was used for pathological judgement. Their medical charts
      were used to investigate their clinical factors. Although patients suspected of
      having encephalitis/meningitis had been hospitalized for 2 days to three months
      during childhood due to disturbance of consciousness with high fever and
      convulsion for several days; they were not diagnosed with encephalitis/meningitis
      at that time, and they suffered almost no handicaps other than epilepsy for
      several years following their comatose episodes. [Result] (1) On MRI, mesial
      temporal sclerosis (MTS) was detected in 48 of 52 patients (92%); 32 (62%) had
      high-signal intensity on T 2-weighted images; 31 (60%) had atrophy ?23 (44%) had
      high-signal intensity on T 2 + atrophy?; 5 (10%) had calcified lesions; and 2
      (4%) had cystic lesions. On PET and SPECT, abnormal cerebral blood flow was noted
      in 33 of 36 (92%). (2) On pathological findings (61 cases), Ammon's horn
      sclerosis (AHS), tumors, gliosis in lateral temporal and meningeal inflammatory
      finding were detected in 42 (69%), 10 (23%) and 8 (13%) cases, respectively,
      whereas 2 showed no abnormalities. The 2 patients with normal pathology showed
      both high-signal intensity and atrophy on MRI. (3) The presumed causes of TLE
      were encephalitis/meningitis and/or suspected of these diseases in 15 patients
      (24%), injuries at birth in 5 (8%), and none in 42 (68%). The presumed causes in
      the 43 patients with AHS were encephalitis/meningitis in 11, injuries at birth in
      3, and none in 29. Of the 15 patients in whom encephalitis/meningitis was
      estimated as the causes of TLE, only 6 (40%) had pathological evidence of
      meningeal inflammatory finding. Of the 42 patients in whom cause could not be
      determined, 2 had pathological evidence of meningeal inflammatory finding.

PMID- 9566004
TI  - [Brain magnetic resonance imaging findings in two cases of Hunter's syndrome].
AB  - Magnetic resonance (MR) imaging findings in two cases of Hunter's syndrome
      [mucopolysaccharidosis (MPS) type II A] are reported. The first case is a 15-year
      old boy in whom the diagnosis of Hunter's syndrome was made at 2 years of age on
      the basis of increased glycosaminoglycans in the urine, developmental delay,
      characteristic faces, joint contraction, family histories, and radiological
      characteristics including oar-like deformed ribs and dysplasia of lumbar
      vertebrae. MR images showed marked enlargement of the lateral ventricles and
      third ventricle. The cerebral cortical sulci were diffusely dilated. Abnormal
      intensity lesions in the lateral part of the lentiform nucleus, the subcortex of
      the insula, the pons, and the right thalamus were seen. Diffuse hyperintensity
      throughout the periventricular white matter is also seen on T2-weighted images.
      The second case is a 3-year-old boy, born at immature delivery. At 2 months of
      age, he was admitted to a pediatric department because of liver dysfunction,
      inguinal hernias and umbilical hernia. The diagnosis of Hunter's syndrome was
      made by developmental delay, gargoylism, joint contraction, kyphosis, and
      biochemical investigation of urine. Urinary glycosaminoglycans significantly
      increased. Skeletal radiography showed dysplasia of the lumbar vertebrae and
      acetabulum. T1-weighted MR images demonstrated numerous hypointense spots in the
      corpus callosum and the cerebral white matter, presumably suggesting large
      perivascular spaces. Multiple cystic changes appeared to be hyperintense on T2
      weighted images. Numerous linear hyperintense lesions were visible in the corona
      radiata. Patchy areas of hyperintense areas were seen, more prominent in the
      parietal lobes. Neuropathological examinations in cases of Hunter's syndrome have
      previously shown marked dilatation of ventricular system, large perivascular
      spaces secondary to mucopolysaccharide storage, demyelination and gliosis in the
      white matter and so forth. MR findings correlated well with previously reported
      neuropathological findings. MR study is not only useful for diagnosing Hunter's
      syndrome but also helpful to follow the pathological status.

PMID- 9566003
TI  - [A case manifested overlapping neuropathologic features of both progressive
      supranuclear palsy (PSP) and corticobasal degeneration (CBD)].
AB  - A 62-year-old man developed clumsiness, vertical ophthalmoplegia, right-side
      dominant parkinsonism, pyramidal signs, limb-kinetic apraxia and dementia. His
      brain MRI and SPECT revealed mild fronto-parietal atrophy and hypoperfusion
      predominately on the right side. At the age of 65, the patient died of sepsis.
      The duration of his illness was approximately 3 years. Clinical diagnosis was
      corticobasal degeneration (CBD). On neuropathological examination, there was no
      neuronal loss and many neurofibrillary tangles (NFTs) in the cerebral cortices.
      Basal ganglia and substantia nigra showed moderate to severe neuronal loss. And
      there were many NFTs and argyrophillic threads (threads) in the subthalamic
      nucleus and nuclei of the brainstem. These findings were almost compatible to
      those of PSP. However, the following findings were atypical for PSP, 1) mild
      atrophy and absence of gliosis in the tegmentum of the brain stem, 2) Mild
      neuronal loss in the subthalamic nucleus and the dentate nucleus without grumose
      degeneration. Furthermore, characteristic findings were noted on modified Gallyas
      Braak stain. Numerous threads and many astrocytic plaques (AP) were shown in
      cerebral cortices, which were particular to CBD cases. So this case demonstrated
      neuropathological findings of both PSP and CBD. Therefore, it was difficult to
      classify this case as either PSP or CBD, and we diagnosed this case as a
      neuropathological overlapping case of both PSP and CBD.

PMID- 9566005
TI  - [A case of neurofibromatosis type I associated with basal meningocele and
      abnormal vessels].
AB  - A 21-year-old man with neurofibromatosis type 1 (NF 1) had many widespread
      cutaneous neurofibroma on his right face. Magnetic resonance imaging (MRI)
      revealed basal meningocele due to dysplasia of the skull base. Carotid and
      vertebral angiograms revealed occlusion of the right internal carotid artery,
      persistent primitive trigeminal artery. We have reviewed the clinical and
      radiographic features of this case of neurofibromatosis, meningocele and cerebral
      arterial abnormalities. NF associated with both intracranial vascular
      malformation and meningocele is very rare, and in our case both were thought to
      arise congenitally as a manifestation of mesodermal dysplasia. Careful follow up
      using MRI and MR angiography should be performed for such patients.

PMID- 9566006
TI  - [Glioma in appearance of multiple metastatic brain tumor on enhanced MRI].

PMID- 9566007
TI  - [CSF flow void phenomenon in thoracic intradural extramedullary region].

PMID- 9566009
TI  - Evidence-based practice.

PMID- 9566008
TI  - [An 81-year-old woman with progressive motor disturbance, extrapyramidal
      features, dementia, and oculomotor palsy].
AB  - We report an 81-year-old woman who presented with motor disturbance in her right
      hand which was followed by parkinsonism, dementia, and supranuclear gaze palsy.
      She was well until her age of 73 (1989) when she had an onset of difficulty in
      using her right hand; she did not have weakness. She also developed small step
      gait. These symptoms had progressively become worse. She was admitted to our
      hospital in July of 1992 when she was 75 years old. On admission, she was alert
      and oriented, but she showed some difficulty in recent memory. She did not have
      aphasia or ideomotor apraxia, but she showed limb-kinetic apraxia in her right
      hand, ideational apraxia, dressing apraxia, constructional apraxia, tactile
      agnosia, and left-right disorientation. Alien-hand syndrome was observed in her
      right hand. Ocular movement was within normal limit for her age. She had oro
      lingual dyskinesia. Otherwise, cranial nerves were intact. She walked in small
      steps. She had rigidity and fine myoclonic movements in her right upper
      extremity. Deep reflexes were within normal limits and symmetric. Superficial and
      deep sensations were intact. Laboratory findings were unremarkable. She was
      discharged on August 15, 1992 for outpatient follow-up. Her motor and mental
      symptoms were progressive. By October of 1992, she developed supranuclear
      vertical gaze palsy, marked rigidity in the neck, and astereognosis. By June
      1993, she became unable to walk without support. MRI taken in May of 1994
      revealed atrophy of insular cortices, temporal lobe tips and parietal lobes more
      on the left side; the third ventricle was slightly dilated. She was admitted to
      another hospital on June 30, 1994. She had become a bed-ridden state with marked
      dementia and dysphagia. She developed fever on November 5, 1996 and expired on
      December 16 of the same year. She was discussed in a neurological CPC and the
      chief discussant arrived at the conclusion that the patient had corticobasal
      degeneration. Other diagnoses entertained included progressive supranuclear
      palsy, pallidonigroluysian atrophy, diffuse Lewy body disease, and Pick's
      disease. But the most of the participants agreed with the chief discussant's
      diagnosis. Post-mortem examination revealed aspiration pneumonia in the lungs and
      liver fibrosis apparently due to viral hepatitis. In the central nervous system,
      frontal and parietal lobes were atrophic more on the left side. Atrophy was
      accentuated in the superior frontal gyri, precentral and postcentral gyri, and
      superior and inferior parietal lobuli. Neuronal loss and astrocytosis were seen
      in these regions with scattered ballooned neurons. The substantia nigra showed
      marked neuronal loss and gliosis; neuronal loss was also seen in the pars
      reticulata. The outer and inner segments of globus pallidus and the
      periacqueductal gray matter showed gliosis, however, no apparent neuronal loss
      was seen. Putamen, subthalamic nucleus, and the dentate nucleus were preserved.
      Pathologic changes were consistent with the diagnosis of corticobasal
      degeneration. It was interesting to note that anti-tau immunostaining and Gallyas
      staining revealed neuropil threads and astrocytic plaques in the cortical areas,
      and intracytoplasmic inclusion bodies in the cortical neurons; these inclusions
      were not stained by Bodian stain. Tuft-shaped astrocytes which may be seen in
      progressive supranuclear palsy were not observed in this patient. Although
      corticobasal degeneration and progressive supranuclear palsy share some
      neurological features in common, this patient showed typical pathologic changes
      of corticobasal degeneration.

PMID- 9566010
TI  - Bonding systems for restorative materials--a comprehensive review.
AB  - The acid-etch technique for bonding composite resins to enamel has revolutionized
      the practice of pediatric restorative dentistry. Although bonding resins to
      dentin has proved to be a difficult challenge, ongoing advances have improved the
      reliability and predictability of dentinal adhesion. The purpose of this paper is
      to review the subject of dentin bonding; its development, current status, and
      clinical methods to improve performance.

PMID- 9566011
TI  - Sealants and preventive restorations: review of effectiveness and clinical
      changes for improvement.
AB  - Sealants are effective caries-preventive agents to the extent they remain bonded
      to teeth. Preventive resin restorations (PRR) have a proven record, but are
      susceptible to failure as the overlying sealant fails. Careful analyses of
      studies reveal a measurable failure rate of sealants (5-10% per year) that must
      be addressed. Even under the best of circumstances, sealants fail. Therefore,
      dentistry (as well as third-party systems) must accept that sealants need
      vigilant recall and proper preventive maintenance. In addition, it is clear that
      cost-effective use of sealants will involve selective application on teeth with
      the greatest caries risk. Caries risk analysis of the patient as well as the
      tooth is an essential step in the treatment planning process. To improve sealant
      success, new material advances are suggested. Data from studies using an
      intermediate layer of dentin bonding agent between etched enamel and sealant show
      dramatic reduction of failure for sealants, particularly in instances of molars
      judged difficult to seal due to early stage of eruption.

PMID- 9566012
TI  - The continuum of restorative materials in pediatric dentistry--a review for the
      clinician.
AB  - Many choices are available to the practitioner of restorative dentistry for
      children. With the introduction of several new classes of restorative materials
      in recent years, some confusion has been created about what these materials are,
      making it difficult to identify their appropriate clinical use. This paper
      reviews glass-ionomer materials, resin-modified (reinforced) glass ionomers,
      compomers, and composite resins for the practitioner. Definitions of these
      materials, a general description of their contents, and usage-selection criteria
      are provided. Although more choices for tooth restoration can make the selection
      of the right material more difficult, a better understanding of the components
      and the strengths and weaknesses of each category of materials offers the
      opportunity to select the right material for the right situation.

PMID- 9566013
TI  - The role of fluoride mouthrinses in the control of dental caries: a brief review.
AB  - Fluoride mouthrinses have generally proved to be effective in controlling caries
      in clinical studies. Caries reductions in North American studies have averaged
      about 30%. Large-scale school-based mouthrinse programs conducted during the
      1970s, however, used historical controls at a time when caries rates were now
      known to be declining. Post-hoc analysis of the absolute (not relative) caries
      reductions in these studies showed that school-based fluoride mouthrinse programs
      were of questionable benefit from a cost standpoint. Fluoride mouthrinses have
      been shown to reduce demineralization and enhance remineralization of enamel
      adjacent to orthodontic bands and brackets. Benefits in adults have been less
      well documented. Use of fluoride mouthrinses by young children is discouraged
      until they have mastery of their swallowing reflexes. This paper recommends the
      use of fluoride mouthrinses for patients at increased or high risk for dental
      caries, but cautions that school-based programs be undertaken only in communities
      with a high population caries rate.

PMID- 9566014
TI  - Effectiveness of electronic dental anesthesia for restorative care in children.
AB  - The effectiveness of electronic dental anesthesia (EDA) for pain control during
      restorative procedures was compared with local anesthetic injection (LA) in 32
      children aged 6 to 12 years. Each child selected had two antimere primary or
      permanent molars requiring similar-sized Class I or Class II restorations. The
      pain levels during restorative treatment were assessed using a visual analogue
      scale. Heart rates and behavior were also recorded. A crossover design was used
      with each child acting as his/her own control. The results showed that overall,
      EDA was less effective than LA for cavity preparation. The reported pain scores
      for EDA were higher in permanent teeth for the deeper cavities, and with one of
      the operators. The pre- or post-treatment anxiety scores were not found to differ
      significantly between the two restorative appointments. However, children with
      the highest pretreatment scores were more likely to report higher pain scores
      with EDA. Despite this, 63% of the children preferred EDA to LA. Dental anxiety,
      cavity depth, the tooth being treated, and operator attitude may also be
      important factors in determining the success of EDA.

PMID- 9566016
TI  - An impacted primary lateral incisor as a cause of delayed eruption of a permanent
      tooth: case report.

PMID- 9566015
TI  - Diagnosis and treatment of dental trauma in a children's hospital.
AB  - A comprehensive review of 487 emergency dental trauma visits seen at a children's
      hospital during a 3-year period was performed to investigate aspects of trauma
      care that have not been previously reported. Patient characteristics, diagnoses,
      and injury treatment were analyzed. General patient characteristics and diagnoses
      were consistent with other studies. Young children were often injured in falls
      within the home whereas older children were often injured in sports and
      activities outside the home. The emergency visit was the first contact with the
      dentist for 80% of children 3.5 years old and younger. Maxillary incisors
      accounted for 84% of primary tooth injuries: examination and extraction were
      common treatments. Maxillary incisors accounted for 87% of permanent tooth
      injuries: bandage restorations and splint placement were frequent treatments. An
      assistive restraint device was used most often for children 4 years and younger
      who required extractions. The restraint was used more frequently during clinic
      hours with support staff present than after hours with a sole provider. Hospital
      facilities were not essential for treatment of the patients in this study.

PMID- 9566017
TI  - Fluoride use by pediatric dentists in Houston.

PMID- 9566018
TI  - Differentiation of the inhibitory effects of calcium antagonists on abnormal
      behaviors induced by methamphetamine or phencyclidine.
AB  - The abnormal behaviors induced by methamphetamine (MAP: 1 mg/kg) or phencyclidine
      (PCP: 10 mg/kg) were measured using behavioral analysis following the
      microinjection of one of three calcium (Ca) antagonists (nifedipine: Nif,
      nicardipine: Nic and flunarizine: Flu) into the rat caudate putamen or amygdala.
      The intraperitoneal administration of MAP or PCP induced abnormal behaviors in a
      time-dependent manner; the maximum locomotor activity was measured 30-45 min
      after the administration of MAP or PCP. This hyperactivity was sustained for more
      than 2 h. Following microinjection of these Ca antagonists into the caudate
      putamen, each showed a different pattern of inhibition on MAP- or PCP-induced
      abnormal behaviors. Nic and Flu were effective at reducing these abnormal
      behaviors, in contrast, Nif was ineffective. In particular, the inhibitory effect
      of Nic was stronger than that of Flu. Microinjection of these Ca antagonists into
      the amygdala did not show any reductive effect on the hyperactivity induced by
      MAP or PCP. These results demonstrate that these Ca antagonists have different
      pharmacological properties and that both L- and T-type Ca2+ channels modulate the
      dopamine release in the rat caudate putamen. These results further lead us to
      suggest the presence of a subtype of L-type Ca2+ channels in the caudate putamen.

PMID- 9566019
TI  - M1, M3 and M5 muscarinic receptors stimulate mitogen-activated protein kinase.
AB  - We report here that the M1, M3 and M5 muscarinic acetylcholine receptor subtypes
      that have been shown to couple to phosphoinositide hydrolysis also activate the
      mitogen-activated protein kinase (MAPK). Pharmacological characterization as well
      as mechanistic details of the activation pathway are presented. Carbachol-induced
      MAPK activation was time- and concentration-dependent at all subtypes.
      Pharmacological characterization of the MAPK response revealed that McN-A-343 was
      a partial agonist at the M1 and M3 subtypes, and that pilocarpine was a partial
      agonist at the M3 and M5 receptors. Carbachol-mediated MAPK activation at these
      receptor subtypes was pertussis toxin and wortmannin insensitive. By contrast,
      both agents significantly inhibited carbachol-induced MAPK activation by the M2
      muscarinic receptor subtype. Furthermore, two independent single point mutations
      in the M1 receptor attenuated carbachol-induced activation of MAPK. Activation of
      MAPK at the M1, M3 and M5 muscarinic receptor subtypes was not dependent on
      intracellular or extracellular Ca2+, but was partially dependent upon protein
      kinase C. These data suggest that activation of MAPK by M1, M3 and M5 muscarinic
      receptors involves protein kinase C-dependent and independent pathways.

PMID- 9566020
TI  - Esculentoside A inhibits tumor necrosis factor, interleukin-1, and interleukin-6
      production induced by lipopolysaccharide in mice.
AB  - Esculentoside A, a kind of saponin isolated from the root of the Chinese herb
      Phytolaca esculenta, is reported to possess potent anti-inflammatory effects in
      acute and chronic experimental models. In the present study, we investigated the
      effects of esculentoside A on the production of tumor necrosis factor (TNF),
      interleukin-1 (IL-1) and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS)
      in mice. In vitro experiments demonstrated that esculentoside A (0.1-10 mumol/l)
      significantly reduced the release of TNF from the peritoneal macrophages derived
      from mice pretreated with thioglycolate. IL-1 and IL-6 secretion was also
      obviously inhibited in a concentration-dependent manner by esculentoside A from
      0.01 to 10 mumol/l. In vivo experiments demonstrated that detectable TNF was
      observed 0.25 h after injection, was maximal at 0.5 h, and returned to baseline
      at 4 h. Maximal production of IL-1 and IL-6 were observed to be 1 and 2 h,
      respectively, after injection of LPS. Pretreatment of mice with 5, 10, or 20
      mg/kg esculentoside A once a day for 7 consecutive days dose-dependently
      decreased the TNF, IL-1 and IL-6 levels in the sera of mice following LPS
      challenge. TNF, IL-1, and IL-6 are important cytokines involved in the
      pathogenesis of inflammatory lesions. Inhibition of inflammatory cytokine
      production may contribute to the anti-inflammatory effects of esculentoside A.

PMID- 9566021
TI  - Heterogeneity of alpha 1-adrenoceptor subtypes mediating noradrenaline-induced
      contractions of the rat superior mesenteric artery.
AB  - The effects of subtype-selective alpha 1-adrenoceptor antagonists on
      noradrenaline-induced contractions of ring segments of rat superior mesenteric
      artery were investigated to determine the subtype(s) of alpha 1-adrenoceptors
      mediating contractions in this preparation. Noradrenaline-induced contractions of
      rat mesenteric artery ring segments were potently and surmountably antagonized by
      prazosin, WB 4101 and BMY 7378. Judging from the slopes of the Schild regression
      lines, which were significantly different from 1, WB 4101 and BMY 7378 behaved as
      noncompetitive antagonists. Spiperone and 5-methylurapidil were only effective at
      high concentrations. Chloroethylclonidine (CEC, 100 mumol/l) displaced the
      noradrenaline concentration-response curve to the right reducing its potency
      approximately 100-fold. Noradrenaline-induced contractions post-CEC were also
      antagonized by prazosin. However, prazosin was less potent against these
      contractions. A 61,603, a selective alpha 1A-adrenoceptor agonist, contracted
      ring segments of the mesenteric artery. These contractions were antagonized by
      prazosin, however with a low affinity, indicating interaction with a low-affinity
      receptor subtype. It was therefore concluded that alpha 1D- and, possibly, alpha
      1L-adrenoceptor subtypes mediated noradrenaline- induced contractions of the rat
      superior mesenteric artery.

PMID- 9566022
TI  - Impaired contraction and relaxation in the aorta of streptozotocin-diabetic rats.
AB  - It is known that diabetes mellitus alters the vascular responsiveness to several
      vasoconstrictors and vasodilators. Endothelium-derived nitric oxide is a potent
      endogenous nitrovasodilator, and endothelin-1 (ET-1) is a potent endothelium
      derived vasoconstrictor substance. They play a major role in the modulation of
      vascular tone. Selective impairment of endothelium-dependent relaxation and
      impaired vasoconstriction in response to ET-1 could result in vascular disorders.
      The purpose of our study was to determine whether vascular responses to ET-1 and
      endothelium-dependent relaxing substances are impaired in rats with
      streptozotocin-induced diabetes of 2 weeks duration. Endothelium-dependent
      relaxations produced by carbachol and ATP in aortic rings precontracted with
      phenylephrine were significantly attenuated in rings from diabetic rats, but the
      endothelium-independent relaxations produced by sodium nitroprusside and
      adenosine in diabetic preparations were not changed when compared to the
      corresponding controls. The ET-1-induced contractions were significantly
      attenuated with no change in agonist potency (pD2 value) in aortae with and
      without endothelium obtained from diabetic rats when compared to those from
      controls. Mechanical removal of the endothelium did not significantly change ET-1
      responses of aortae from either diabetic or control rats compared with responses
      of aortae with intact endothelium. These results suggest that, in this diabetic
      model, the contractile responsiveness of thoracic aortic muscles and the
      endothelial functions are significantly altered during 2 weeks of diabetes.

PMID- 9566023
TI  - Digital analysis of the pharmacological effects of in vitro ischemia on rabbit
      corpus cavernosum.
AB  - PURPOSE: Regulation of corporal smooth muscle tone is essential for the
      initiation of penile erection. In recent years, in vitro isometric tension
      studies using isolated corpus cavernosal tissue have been used extensively to
      investigate the mechanisms regulating corporal smooth muscle tone and tension. In
      the present study, we utilized digital analysis of contractile data generated
      from investigation of contractile and relaxation responses of isolated rabbit
      corpus cavenosum to various forms of stimulation. Digital analysis of the
      contractile and relaxation data allows quantitation of both maximal and mean
      rates of tension change, and time elapsed to maximal response. Rates of tension
      changes may provide additional important information regarding cellular events
      that mediate corporal tone and tension changes. METHODS: Sexually mature male New
      Zealand White rabbits were used. Each corpus cavernosum was dissected sharply
      from the removed penis, then two longitudinal strips were prepared for isometric
      tension studies and placed in individual baths. Tension was monitored continually
      using an 8-channel Grass Polygraph. The Grass PolyVIEW system simultaneously
      converted analog signals to digital information and stored data using a 486 PC
      computer. Each corporal strip was prestimulated with 300 mumol/l phenylephrine to
      produce a maximal contraction, then field stimulation (FS), carbachol and
      nitroprusside were applied consecutively to determine relaxation effects. This
      procedure was repeated after strips were deprived of glucose and oxygen (in vitro
      ischemia) for 1 h. The following parameters were quantitated for all responses:
      maximal tension change; maximal and mean rates of tension change, and time to
      maximal response. RESULTS: Effects of 1-hour in vitro ischemia on rabbit corporal
      tissue were as follows: (1) an 85% decrease in contractile response to
      phenylephrine, and (2) a marked increase in rate of contractile response to
      phenylephrine. Phenylephrine precontracted strips exhibited: (3) no change in
      relaxant response to FS; (4) increased relaxant responses to carbachol and
      nitroprusside; (5) no change in rates of relaxation in response to FS; (6)
      increased rates of relaxation in response to carbachol and nitroprusside, (7) no
      change in elapsed time to maximal relaxation in response to FS, and (8) decreased
      elapsed time to maximal relaxation in response to carbachol and nitroprusside.
      CONCLUSION: Digital analysis of the data generated facilitates recording,
      reviewing and analyzing of in vitro isometric tension studies on rabbit corpus
      cavernosum. Digital analysis allows quantification of additional parameters that
      have important implications for determination of mechanisms by which specific
      pathological processes occur.

PMID- 9566024
TI  - Professor Jerzy Maj on his 75th birthday.

PMID- 9566025
TI  - Presence and function of dopamine D1 receptors in the rat ventral tegmental area.
AB  - In the recent years there is a growing number of reports suggesting that dopamine
      D1 receptors are involved in the phenomenon of sensitization. In this article we
      are reviewing the data suggesting the crucial role of dopamine D1 receptors,
      localized in the rat ventral tegmental area in this phenomenon.

PMID- 9566026
TI  - Prolonged treatment with beta-adrenoceptor antagonists counteracts the aggression
      deficit induced by chronic stress.
AB  - Chronic stress-induced behavioral disturbances have been used as experimental
      models of depression. One of them is the deficit of fighting behavior induced by
      16-day application of various unpredictable stressors. In the present study we
      investigated the effect of beta-adrenoceptor antagonists (propranolol, pindolol,
      nadolol and acebutolol) on electric footshock-induced fighting behavior in
      chronically stressed (14 various stressors over 16 days) male Wistar rats. It was
      found that the number of fighting attacks was reduced by about 50-80% in the rats
      submitted to chronic stress. Prolonged, 14-day, but not acute, treatment with
      propranolol, pindolol or nadolol (but not acebutolol) counteracted the deficit of
      aggression induced by chronic stress. It is suggested that beta-adrenoceptor
      antagonists which penetrate the blood-brain barrier may prevent the behavioral
      changes induced by chronic stress.

PMID- 9566027
TI  - Nitric oxide (NO) pathway and locomotor hyperactivity towards dopaminomimetics in
      rats.
AB  - The effects of the NO donor molsidomine and the inhibitors of the NO synthase
      (NOS) 7-nitroindazole (7-NI) and NG-nitro-L-arginine methyl ester (L-NAME) on the
      motor hyperactivity induced by indirect (amphetamine and cocaine) or direct (SKF
      38393 and bromocriptine) dopamine (DA) agonists were studied in rats. The
      hyperactivity induced by 0.5 mg/kg of amphetamine or 5 mg/kg of cocaine was
      potentiated in a dose-dependent manner by molsidomine (30-100 mg/kg), but
      attenuated by 7-NI (3-30 mg/kg) or L-NAME (3-30 mg/kg). The NOS inhibitors also
      inhibited the locomotor hyperactivity evoked by 15 mg/kg of SKF 38393 (a DA D1
      agonist) or 5 mg/kg of bromocriptine (a DA D2 agonist). On the other hand, the
      hyperactivity induced by those direct DA receptor agonists was potentiated by
      molsidomine. The present findings provide further evidence for an interaction at
      the behavioral level between NO and the DA-mediated effects of amphetamine and
      cocaine; moreover, they seem to indicate that both DA D1 and DA D2 receptor
      subtypes are under such influence.

PMID- 9566028
TI  - Involvement of 5-hydroxytryptamine 2A (5-HT2A) receptors in the mediation of the
      discriminative stimulus properties of (+/-)DOI in rats.
AB  - Rats were trained to discriminate between the 5-HT2A/2C receptor agonist (+/-)1
      (2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI, 0.35 mg/kg] and saline
      using a two-lever drug discrimination procedure; afterwards, the effects of
      different 5-HT agonists and antagonists on the discriminative stimulus properties
      induced by (+/-)DOI were studied. In substitution tests, D-lysergic acid
      diethylamide (LSD, 0.02 and 0.04 mg/kg) and quipazine (0.5, 1.5 and 3 mg/kg), 5
      HT2A/2C agonists, evoked dose-related responses to the (+/-)DOI-appropriate
      lever, while the non-selective 5-HT agonist 1-(3-chlorophenyl)piperazine (m-CPP,
      0.1, 0.5 and 1 mg/kg), which has the highest binding affinity for 5-HT2C
      receptors, failed to show substitution. In antagonist studies, the discriminative
      stimulus effect of (+/-)DOI was completely antagonized by ketanserin (0.5 mg/kg)
      and cyproheptadine (0.5 mg/kg), preferential 5-HT2A receptor antagonists, and
      partially by the 5-HT2A/2C receptor antagonist mesulergine (0.25, 0.5 and 1.0
      mg/kg) and the 5-HT2A/D2 antagonist spiperone (0.025, 0.05 and 0.1 mg/kg). The
      above data suggest that the discriminative stimulus effects of (+/-)DOI are
      predominantly mediated by 5-HT2A receptors.

PMID- 9566029
TI  - Impact of metyrapone on MK-801-induced alterations in the rat dopamine D1
      receptors.
AB  - Our earlier studies have shown that changes in serum corticosterone levels played
      an important role in the acquisition of sensitization to MK-801, a non
      competitive NMDA receptor antagonist. Dopaminergic mechanisms are found to be
      particularly important in the development of sensitization; hence in the present
      study we assessed the binding of [3H]SCH 23390 at brain dopaminergic D1
      receptors, after administration of MK-801 (0.4 mg/kg), in rats in which
      corticosterone synthesis was inhibited by metyrapone (150 + 50 mg/kg). Such
      metyrapone pretreatment prevented the increases in serum corticosterone level
      induced by MK-801. The binding studies, using receptor autoradiography, were
      performed in the following brain structures: the striatum, nucleus accumbens,
      olfactory tubercle and substantia nigra. Metyrapone per se did not change or
      slightly increased D1 receptor binding in the substantia nigra, while in other
      brain structures tested it decreased the number of these receptors by about 30%.
      MK-801 increased the level of D1 receptors in the nucleus accumbens core and
      olfactory tubercle, being without effect in the remaining brain structures
      tested. In rats which were pretreated with metyrapone, the effect of MK-801 on D1
      receptors was inhibited in the nucleus accumbens core only. In substantia nigra,
      metyrapone provoked the MK-801-induced decrease in D1 receptors whereas in all
      other structures MK-801 reversed the effects of metyrapone on D1 receptors.
      Additionally, the effect of metyrapone and MK-801 on grooming behavior induced by
      D1 receptor agonist SKF 38393 (10 mg/kg) was tested. Metyrapone did not influence
      grooming induced by SKF 38393, but significantly potentiated the inhibitory
      effect of MK-801 on this behavior. Finally, we found that metyrapone did not
      influence the expression of the sensitization induced by MK-801. Our results seem
      not to support hypothesis that MK-801 evokes enhancement of dopaminergic
      neurotransmission (at the level of D1 receptors) via corticosterone liberation,
      since in most brain regions studied inhibition of increases in corticosterone
      level did not prevent MK-801-induced effects on D1 receptors. The present study
      may suggest that NMDA receptors are involved in the corticosterone-dependent
      regulation of the density of the D1 receptors.

PMID- 9566030
TI  - Adenosine receptors--the role in modulation of dopamine and glutamate release in
      the rat striatum.
AB  - The aim of present study was to assess the role of activation of adenosine A-1
      and A-2a receptors in the modulation of dopamine (DA) and glutamate release in
      the rat striatum by microdialysis in freely moving animals. Adenosine A-1
      receptor agonist N6-cyclopentyladenosine (CPA) and A-2a receptor agonist 2-p-(2
      carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) were
      administered locally into the striatum through microdialysis probe. CPA (10, 100
      and 500 microM) did not affect basal levels of DA or glutamate. In contrast, CGS
      21680 at the concentrations of 10, 50 and 100 microM increased in a dose
      dependent manner the level of DA and at 100 microM also the level of glutamate.
      Both agonists at the concentration of 100 microM inhibited KCl-induced (100 mM)
      DA and glutamate release. The present results suggest, that in physiological
      conditions only excitatory effects of adenosine may be observed and adenosine A
      2a receptors seem to be involved. During depolarization with KCl, adenosine, by
      inhibiting excessive outflow of neurotransmitters mediated via A-1 and A-2a
      receptors, manifests its protective role as homeostatic neuromodulator.

PMID- 9566031
TI  - Haloperidol-induced catalepsy is influenced by adenosine receptor antagonists.
AB  - Cataleptogenic effects of haloperidol (1 mg/kg i.p.) in rats was antagonized by
      caffeine and theophylline (10-50 mg/kg i.p.), and by selective adenosine A2
      receptor antagonist (3,7-dimethyl-1-propargylxanthine) (3 and 6 mg/kg i.p.).
      Selective A1-adenosine receptor antagonist (8-cyclopentyltheophylline) (1.5 and 3
      mg/kg i.p.) was not able to reduce this effect of haloperidol. These results
      confirm the antagonistic interaction between adenosine A2A and dopamine D2
      receptors, and suggest the involvement of adenosine A2 receptors in the
      mechanisms of catalepsy.

PMID- 9566032
TI  - Effect of 1,3-di-o-tolylguanidine (DTG), rimcazole and EMD 57445, the sigma
      receptor ligands, in the forced swimming test.
AB  - As it is known, sigma receptor ligands have been able to modulate the central
      neurotransmitter systems, including noradrenergic-, NMDA-ergic- and dopaminergic
      ones, which are essential for the mechanism of action of antidepressant drugs.
      Therefore, it can be assumed that some selective sigma ligands can possess
      antidepressant-like activity. In the present studies 1,3-di-o-tolylguanidine
      (DTG), rimcazole (RIM) and EMD 57445 were examined in the forced swimming test in
      rats and mice. DTG and RIM decreased the immobility time in mice. EMD 57445 was
      inactive but it antagonized the anti-immobility effects of DTG and RIM. Both
      latter drugs did not change the locomotor activity of mice, EMD 57445 at higher
      dose decreased it. In addition, DTG showed antidepressant-like activity in rats,
      this effect being counteracted by EMD 57445. At the same time both drugs
      attenuated the spontaneous motor activity in rats. Taken together, the present
      results suggested that DTG and RIM may possess sigma agonistic activity while EMD
      57445--the antagonistic one. Further investigations are needed to support
      agonistic/antagonistic activities of the studied sigma ligands and to elucidate
      the potential involvement of sigma site subtypes in this model.

PMID- 9566033
TI  - Time-dependent effects of antidepressant drugs on the low dose of apomorphine
      induced locomotor hypoactivity in rats.
AB  - In the present study the hypothesis of antidepressant-induced subsensitivity of
      presynaptic dopamine receptors was readdressed. We used the behavioral model of
      low dose of apomorphine-induced locomotor hypoactivity in rats. Indeed, repeated
      administration of imipramine and citalopram attenuated the effect of low dose of
      apomorphine. However, the most interesting finding of the present study was the
      observation that similar and even stronger attenuation of low dose of apomorphine
      induced hypoactivity was obtained by the acute treatment with imipramine,
      citalopram and amitriptyline, followed by 14 drug free days. That means that the
      acute antidepressant drug treatment seems to be sufficient to trigger the changes
      at the level of dopamine D2 presynaptic receptors and/or signal transduction
      mechanisms as a function of time, regardless of whether the drug is again
      administered. On the other hand, such the effect of time was not observed in the
      experiments using D-amphetamine as a motor stimulant. Only the repeated
      administration of antidepressant drugs enhanced the locomotor hyperactivity
      induced by D-amphetamine. Acute treatment, neither 2 h nor 14 days after the last
      dose, changed the D-amphetamine-induced hyperactivity. Such a difference in the
      time-dependent effects of antidepressant drugs on the locomotor activity induced
      by either the low dose of apomorphine or D-amphetamine may possibly result from
      the different mechanisms involved in the regulation of the biosynthesis of
      dopamine presynaptic and postsynaptic receptors in the rat brain.

PMID- 9566034
TI  - Imipramine-induced subsensitivity to the 5-HT4 receptor activation, a possible
      mediation via an alteration in the postreceptor transduction mechanism involving
      adenylate cyclase.
AB  - The effects of repeated treatment with imipramine on the reactivity of CA1
      neurons in the rat hippocampus to the 5-HT4 receptor agonist zacopride and the
      direct adenylate cyclase activator forskolin were compared ex vivo to assess
      whether a modulation of signal transduction pathway may contribute to the
      antidepressant-induced adaptive changes in the responsiveness of pyramidal
      neurons to 5-HT4 receptor activation. The population spike recorded in the CA1
      cell layer was a measure of pyramidal cell excitability, while the dendritic
      field excitatory postsynaptic potential (fEPSP) recorded in the stratum radiatum
      of the CA1 region was employed to assess the effects of the tested drugs on the
      excitatory amino-acid-mediated synaptic transmission. Zacopride (5 microM) and
      forskolin (1 microM) increased the amplitude of the half-maximal population spike
      (by 37 +/- 5% and 42 +/- 4%, respectively). Forskolin, but not zacopride,
      increased the slope of the fEPSP (by 13 +/- 2%). Repeated treatment with
      imipramine (14 days, twice daily, 10 mg/kg po) attenuated the excitatory effect
      of zacopride and forskolin on the population spike and the effect of forskolin on
      the fEPSP. It is concluded that the reduction in the responsiveness of CA1 cells
      to zacopride, induced by repeated administration of imipramine, may be due to
      modifications of the signal transduction pathway, i.e. adenylate cyclase and
      protein kinase A, which is responsible for the 5-HT4 receptor-mediated decrease
      in the activity of potassium channels.

PMID- 9566035
TI  - Imipramine induces alterations in proenkephalin and prodynorphin mRNAs level in
      the nucleus accumbens and striatum in the rat.
AB  - Endogenous opioids have been implicated in the mechanism of action of
      antidepressant drugs. In this study, we evaluated effects of single and repeated
      imipramine administration on proenkephalin and prodynorphin gene expression in
      the rat nucleus accumbens and striatum. In situ hybridization study showed that
      single imipramine injection (10 mg/kg, i.p.) decreased the level of proenkephalin
      (by ca. 20%) and prodynorphin (by ca. 25%) mRNA to the same extent in both
      structures. Repeated imipramine administration (10 mg/kg i.p. twice daily for 10
      days) had no effect on proenkephalin mRNA level, whereas the prodynorphin gene
      expression was regulated differently. At 3 h after the last dose of imipramine
      the prodynorphin mRNA level was decreased (by ca. 25%) in the striatum, but not
      in the nucleus accumbens, whereas at 24 h an up-regulation (by ca. 27%) of
      prodynorphin mRNA level could be observed in the nucleus accumbens only. In the
      light of involvement of opioids in mood regulation, these adaptive changes may
      participate in neurochemical mechanisms of antidepressant therapy.

PMID- 9566036
TI  - Activation of metabotropic glutamate receptors increases neuropeptide Y
      expression in the rat hippocampus. Immunohistochemical studies.
AB  - Neuropeptide Y (NPY), a 36-amino acid peptide, is present in some hippocampal
      interneurons and nerve terminals and seems to modulate glutamatergic transmission
      in this structure. Earlier studies of some other authors showed an increase in
      NPY expression in the hippocampus during seizures and activation of ionotropic
      glutamate receptors. In the present study the effect of metabotropic glutamate
      receptor (mGluR) stimulation was investigated in rat hippocampus by
      immunohistochemical methods. It was found that (1S,3R)1-aminocyclopentane-1,3
      dicarboxylic acid (1S,3R-ACPD), a selective agonist of mGluRs injected into the
      rat lateral ventricle (1 mumol/10 microliters) or hippocampus (0.1 mumol/1
      microliter), 24 h before taking the brains for immunohistochemical studies,
      induced a significant increase in NPY-immunoreactivity in the hippocampus,
      especially in the hilar region. The obtained results indicate that mGluRs
      positively modulate the NPY content in the hippocampal neurons.

PMID- 9566037
TI  - Effect of nitric oxide synthase inhibitors and molsidomine on the anticonvulsant
      activity of some antiepileptic drugs.
AB  - The present study examined effects of the two nitric oxide synthase (NOS)
      inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI),
      as well as of the NO donor molsidomine on the anticonvulsant activity of
      conventional antiepileptic drugs (diphenylhydantoin and carbamazepine) and
      competitive (CGP 37,849) and non-competitive (dizocilpine) NMDA receptor
      antagonists against the maximal electroshock in mice. It was found that L-NAME
      (25 and 50 mg/kg) did not affect the anticonvulsant activity of either drug,
      having had no influence on their anticonvulsive ED50 values. 7-NI (50 and 100
      mg/kg) reduced the anticonvulsive ED50 (augmentation of the anticonvulsant
      activity) of CGP 37,849 and dizocilpine, raised the anticonvulsive ED50
      (attenuation of the anticonvulsant activity) of diphenylhydantoin and had no
      influence on the anticonvulsant effect of carbamazepine. At the same time,
      augmentation of the anticonvulsant activity (reduction of the ED50 values) of
      diphenylhydantoin, carbamazepine and CGP 37,849, but not of dizocilpine, was
      observed after molsidomine (100-150 mg/kg). Moreover, 7-NI (100 mg/kg) and
      molsidomine (100 and 150 mg/kg), but not L-NAME (25 and 50 mg/kg), raised the
      threshold for electroconvulsions. The obtained results indicate that alterations
      in the anticonvulsant activity of the investigated drugs evoked by 7-NI and
      mosidomine, may result from non-specific effects of the NOS inhibitor and the NO
      donor, having no connection with the brain NO pathway.

PMID- 9566038
TI  - Role of voltage dependent calcium channels and cholinergic receptors in the
      convulsant action of BAY k-8644.
AB  - The study was designed to investigate the effects of administration of
      cholinomimetic agents and nifedipine on seizures induced by BAY k-8644 in rats.
      Injection of pilocarpine (3 mg/kg) increased seizures induced by BAY k-8644 (2
      mg/kg). Administration of nifedipine (10 mg/kg) did not affect the convulsions
      and mortality elicited by coadministration of BAY k-8644 and pilocarpine.
      However, the facilitating effect of pilocarpine on BAY k-8644-induced seizures
      was fully prevented by pretreatment of rats with a cholinergic antagonist
      atropine (5 mg/kg). No similar effects were observed after injection of another
      cholinomimetic agent physostigmine (0.3 mg/kg). This finding implies, that
      facilitation of convulsant action of BAY k-8644 by pilocarpine may be related to
      activity of cholinergic system, but not strictly to activity of voltage dependent
      calcium channels.

PMID- 9566039
TI  - Protective effects of TRH and its analogues in chemical and genetic models of
      seizures.
AB  - TRH shows strong influence on neuronal excitability and may participate in the
      regulation of seizures. We investigated the effect of TRH and its stable
      analogues on seizures induced by intravenous (i.v.) infusion of pentetrazole in
      rats. The data showed that i.v. administration of TRH (10 and 20 mg/kg), RGH-2202
      (0.1 mg/kg) and Z-p-Glu-His-Pro-NH2 (10 mg/kg) increased threshold for
      pentetrazole-induced clonic seizures, but did not affect the tonic ones. Another
      stable analogue of TRH, 1p-Glu-Tyr-Pro-NH2 (0.1-10 mg/kg), had no effect on
      pentetrazole-induced seizures. In further study, effects of TRH and RGH-2202 were
      examined in WAG/Rij rats, a genetic model of absence epilepsy. TRH (25 and 50
      micrograms i.c.v.) decreased dose-dependently the number and mean duration of
      spike-wave discharges in cortical EEG of WAG/Rij rats at 90 and 120 min after the
      peptide administration. On the other hand, RGH-2202 (1 microgram i.c.v.)
      significantly decreased only the number of spike-wave discharges at 60 min post
      injection. These results confirm that TRH and some of its analogues have moderate
      antiepileptic activity.

PMID- 9566040
TI  - Chronic electroconvulsive treatment increases the activity of nitric oxide
      synthase in the rat brain.
AB  - Activation of the NMDA receptor complex increases the intracellular free Ca2+
      concentration, which in turn influences a nitric oxide synthase (NOS) activity.
      In this study we investigated the NOS activity after acute and chronic
      electroconvulsive treatment in different rat brain regions. Chronic (10 daily
      treatments) but not acute (single treatment) significantly increased the NOS
      activity by 60% in the cerebral cortex and by 20-30% in hippocampus and
      cerebellum. The increased NOS activity might be a compensatory mechanism which
      balanced the reduced NMDA receptor complex reactivity. In fact, the adaptation of
      the NMDA receptor complex induced by chronic electroconvulsive treatment (and
      antidepressant drugs) measured at the receptor level, suggests the subsensitivity
      of that complex. Present results support the hypothesis of the critical role of
      the NMDA receptor pathway in the mechanism of antidepressant action.

PMID- 9566041
TI  - Participation of the multispecific organic anion transporter in hepatobiliary
      excretion of glutathione S-conjugates, drugs and other xenobiotics.
AB  - Polarized liver cells, hepatocytes, are involved in carbohydrate, protein and fat
      metabolism, breakdown of hemoglobin and production of bile. They are also
      involved in overall detoxification processes in an organism associated with the
      transport of bile salts, cholesterol, phospholipids, endo- and xenobiotics, end
      products of cellular metabolism and ions through the canalicular region of the
      hepatocyte plasma membrane. Uptake of the above-mentioned compounds into
      hepatocytes through the basolateral region of plasma membrane is followed by
      their chemical modification by enzymes of detoxification phase I (e.g.
      cytochromes P-450) and phase II (e.g. glutathione S-transferases). Canalicular
      transport participates in phase III of detoxification, and the molecular
      machinery involved in this process is localized in the canalicular region of the
      plasma membrane. Canalicular transport includes the following transport systems:
      a specific canalicular transporter for bile salts, a multidrug resistance 2 P
      glycoprotein (MDR2) participating in the transport of lipids, a multidrug
      resistance 3 P-glycoprotein (MDR3) responsible for the transport of organic
      cations and the multispecific organic anion transporter (cMOAT) involved in the
      transport of non-bile acid organic anions. The cMOAT transport system is
      discussed in this detailed review.

PMID- 9566042
TI  - Studies on the antinociceptive effects of sodium nitroprusside and molsidomine in
      mice.
AB  - The participation of nitric oxide (NO) in antinociceptive activity of molsidomine
      and sodium nitroprusside (SNP) was studied in mice using the writhing test.
      Molsidomine (300 and 150 mg/kg) and SNP (1.52-0.38 mg/kg) induced antinociception
      that was antagonized by naloxone. L-arginine (500-62.5 mg/kg) did not produce
      antinociceptive effects, whereas N omega-nitro-L-arginine methyl ester (L-NAME)
      (37.5-150 mg/kg) induced antinociception which was suppressed by naloxone.
      Methylene blue did not change the molsidomine- and SNP-induced antinociception,
      but significantly intensified that produced by L-NAME. L-arginine increased
      antinociceptive effect of molsidomine but not that of SNP. Antinociceptive
      activity of L-NAME was partially reversed by L-arginine. D-arginine failed to
      influence these effects. The present findings suggest that the NO-cGMP pathway is
      not involved in the mechanism of molsidomine- and SNP-induced antinociception in
      the writhing test in mice.

PMID- 9566044
TI  - Effects of neurosteroids on kainate-induced seizures, neurotoxicity and lethality
      in mice.
AB  - In the present study we examined effects of some neurosteroids on the kainate
      induced seizures, lethality and neurotoxicity in mice. We found that 5 alpha
      pregnan-3 alpha-ol-20-one (allopregnanolone; 10 and 20 mg/kg) markedly elevated
      CD50 for kainate-induced convulsions, whereas 5 beta-pregnan-3 alpha-ol-20-one, 5
      alpha-pregnan-3 alpha-ol-11,20-dione, 5 alpha-androstan-3 alpha-ol-17-one,
      dehydroepiandrosterone sulfate, pregnenolone sulfate and aminosteroid (U-107)
      were ineffective in that test. Furthermore, 5 alpha-pregnan-3 alpha-ol-20-one (5
      20 mg/kg), 5 beta-pregnan-3 alpha-ol-20-one (20 mg/kg) and 5 alpha-androstan-3
      alpha-ol 17-one (10 and 20 mg/kg) decreased, while dehydroepiandrosterone sulfate
      (25 and 50 mg/kg) and pregnenolone sulfate (25 mg/kg) elevated the kainate
      induced lethality in mice. A histological analysis showed that kainate caused a
      dose-dependent neuronal loss of CA1 and CA3 hippocampal fields. Of the
      neurosteroids tested, only allopregnanolone attenuated the kainate-induced
      neurotoxicity. The above data indicate that neurosteroids exert moderate effects
      on seizures and neurotoxic effects of kainate. On the other hand, neurosteroids
      with a GABAA receptor agonistic or antagonistic activity decrease or increase,
      respectively, the kainate-evoked lethality.

PMID- 9566043
TI  - Age-related changes in glutamate receptors: an autoradiographic analysis.
AB  - The aim of the present study was to evaluate age-related changes in NMDA and AMPA
      receptors in old female rats. To this end a quantitative autoradiography of [3H]
      MK-801 and [3H]-AMPA binding was performed in the brain of young (3-month-old),
      middle-aged (12-month-old) and old (36-month-old) rats. Moreover, the binding of
      [3H]-spiperone to D2 dopamine receptors was also examined. No changes were
      observed in the binding of [3H]-MK-801 or [3H]-AMPA in middle-aged rats compared
      to young ones. In the caudate-putamen and shell and core of the nucleus accumbens
      septi of old rats, a pronounced decrease in the [3H]-MK-801 binding and a
      decreasing tendency in the [3H]-AMPA binding were observed. Furthermore, the
      binding of [3H]-MK-801 and [3H]-AMPA was reduced in the hippocampal formation
      and, additionally, a marked decline in the [3H]-MK-801 binding in different parts
      of the cerebral cortex including the frontal, parietal, cingulate, pyriform and
      insular cortices was found. The [3H]-spiperone binding progressively decreased
      with age in the dorsolateral, ventrolateral and medial caudate-putamen. The
      present results show that aging processes lead to changes in the binding of both
      [3H]-MK-801 to NMDA and [3H]-AMPA to AMPA receptors in a number of structures, a
      phenomenon which may reflect motor and memory disturbances found in old rats and
      elderly humans.

PMID- 9566045
TI  - Effects of cholecystokinin, caerulein and pentagastrin on arterial blood pressure
      and plasma renin activity in rats.
AB  - Effects of cholecystokinin (CCK-33), caerulein (CER) and pentagastrin (PG) on
      arterial blood pressure and plasma renin activity (PRA) were studied in rats. The
      results showed that CCK-33 (106.25, 212.5 and 425.0 pmoles/kg i.v.) increased
      systolic and diastolic blood pressure and decreased PRA. CER used at doses: 0.37,
      1.85 and 3.7 nmoles/kg (i.v.) did not change systolic blood pressure. CER
      administered at the higher doses slightly decreased diastolic blood pressure,
      evoked bradycardia and increased PRA. PG used at doses of 0.13, 1.3 and 13.0
      nmoles/kg (i.v.) and the peptide given at the highest dose (13.0 nmoles/kg, i.v.)
      slightly increased arterial blood pressure. PG administered at all doses did not
      change PRA. This research shows that in spite of similarity in biochemical
      structure of CCK-33, CER, PG there are differences in effects of the studied
      peptides on arterial blood pressure and PRA. The correlation between an influence
      of CCK-33, CER and PG on arterial blood pressure and PRA was also observed.

PMID- 9566046
TI  - Thapsigargin attenuates the potentiation of positive inotropic effect of digoxin
      induced by pretreatment with rimalkalim in the guinea pig heart.
AB  - The influence of thapsigargin, a selective inhibitor of sarcoplasmic reticulum
      (SR) Ca2+ ATPase, on the positive inotropic effects of digoxin before and after
      pretreatment with rimalkalim [(3S,4R)-3-hydroxy-2,2-dimethyl-4-(oxopyrrolidinyl)
      6-phenyl-su lfonylchroman hemihydrate (formerly HOE 234)], a known activator of
      ATP-sensitive K+ channels, was studied in the guinea pig heart. The isolated
      papillary muscles from the guinea pig heart were used to study these effects. The
      following parameters were measured: force of contraction (Fc), rate of rise
      (+dF/dt) and rate of fall (-dF/dt) of Fc, time to peak contraction (ttp) and time
      to 10% of the total amplitude of force (tt10). After pretreatment with rimalkalim
      (1 microM), digoxin caused a significant increase in the amplitude of Fc and
      significant shortening of ttp and tt10 (p < 0.05 compared with the values
      obtained with digoxin alone). Thapsigargin (1 microM), a selective inhibitor of
      sarcoplasmic reticulum Ca2+ ATPase, added to rimalkalim, prevented the
      enhancement of the amplitude of Fc induced by digoxin after pretreatment with
      rimalkalim but had no significant influence on the effects of digoxin itself. The
      results demonstrate significant influence of activation of KATP channels on
      digoxin-induced positive inotropic effects in the guinea pig heart. Attenuation
      of this effects of rimalkalim by addition of thapsigargin suggests that
      activation of SR Ca2+ ATPase can be included in this interaction.

PMID- 9566048
TI  - Pharmacokinetics of thioridazine and its metabolites in blood plasma and the
      brain of rats after acute and chronic treatment.
AB  - This study was aimed at investigation of the pharmacokinetics of thioridazine and
      its metabolites after a single and repeated administrations. Male Wistar rats
      received thioridazine as a single dose (10 mg/kg i.p.) or they were treated
      chronically with the neuroleptic (10 mg/kg i.p., twice a day for two weeks).
      Plasma and brain concentrations of thioridazine and its metabolites (N
      desmethylthioridazine, mesoridazine, sulforidazine, and the ring sulfoxide) were
      determined using the HPLC method. The obtained data showed that sulfoxidation in
      position 2 of the thiomethyl substituent and in the thiazine ring are main
      metabolic pathways of thioridazine, and showed that, in contrast to humans, in
      the rat N-desmethylthioridazine is formed in appreciable amount. The
      biotransformation of thioridazine was rather fast yielding plasma peak
      concentrations of metabolites lower than that of the parent compound. The maximum
      concentrations of thioridazine and its metabolites in the brain appeared later
      than in plasma. The peak concentrations and AUC values of thioridazine and its
      metabolites were higher in the brain than in plasma and this corresponded well
      with their longer half-lives in the brain as compared to plasma. The drug was not
      taken up by the brain as efficiently as other phenothiazines. Chronic treatment
      with thioridazine produced significant increases (with the exception of
      thioridazine ring sulfoxide) in the plasma concentrations of the parent compound
      and its metabolites which was accompanied with the prolongation of their plasma
      half-lives. The observed plasma levels of thioridazine were within 'therapeutic
      range' while the concentrations of its metabolites were relatively lower as
      compared to those observed in psychiatric patients. The increased plasma
      concentrations of thioridazine and its metabolites observed in plasma after
      chronic treatment were not followed by parallel changes in the brain.

PMID- 9566047
TI  - Effect of prostaglandin F2 alpha on free radical generation, glutathione content
      and microsomal oxidase activities in rat liver microsomes induced either by
      ethanol or acetone.
AB  - We studied the effect of prostaglandin F2 alpha on parameters related to
      microsomal metabolism (free radical production and lipid peroxidation,
      glutathione content and activity of microsomal oxidases) after an induction by
      ethanol or acetone combined with starvation. Long-term ethanol administration led
      to a significant increase in lipid peroxide formation and NADPH-dependent
      chemiluminescence amplified by luminol and lucigenin. At the same time hydrogen
      peroxide production and NADPH-stimulated lipid peroxidation were enhanced
      although the effect did not reach the level of statistical significance. The
      concentration of reduced glutathione (GSH) in the liver was decreased 2-fold,
      whereas oxidized glutathione (GSSG) content remained unaltered. Ethanol
      intoxication resulted in an increase in 7-ethoxycoumarin-O-deethylase (ECOD), 7
      benzyloxycoumarin-O-deethylase (BCOD) and 7-ethoxy-resorufin-O-deethylase (EROD)
      activities, whereas 7-pentoxyresorufin-O-deethylase (PROD) and ethylmorphin-N
      demethylase (EMND) activities were unaltered. The combination of acetone
      treatment with starvation resulted in a significant increase in lipid and
      hydrogen peroxide formation, NADPH-dependent lipid peroxidation and
      chemiluminescence. GSH and GSSG concentration in the liver dramatically decreased
      5- and 3-fold, respectively. The acetone treatment led to significant increase in
      EROD, ECOD, BCOD, PROD and EMND activities. The treatment of ethanol-intoxicated
      rats with prostaglandin F2 alpha (PGF2 alpha) exerted more pronounced prooxidant
      effect on liver than action of alcohol itself. At the same time, PGF2 alpha
      improved most of parameters changed by acetone treatment combined with
      starvation, decreasing lipid peroxide and radical formation and enhancing GSH and
      GSSG contents.

PMID- 9566050
TI  - Pharmacokinetic-stereoselective differentiation of some isomeric analogues of
      ifosfamide.
AB  - Three bromine-ifosfamide analogues: racemic chlorobromofosfamide (+/-)-(R,S)-1,
      its levorotatory enantiomer (-)-(S)-2 and racemic bromofosfamide (+/-)-(R,S)-3
      showed considerable stereoselective differences in their pharmacokinetics and
      bioavailability depending on the route of administration and regimen of dosage
      studies in rats. Remarkable differences in the AUCi.p. parameters (212, 54, 89
      mumol x min x ml-1, respectively) were demonstrated in comparison with a standard
      ifosfamide (158 mumol x min x ml-1). However, the AUCp.o. established for (+/-)
      (R,S)-1 and (-)-(S)-2 were similar and different from the value measured for (+/
      )-(R,S)-3. A wide variability in the determined parameters after i.p. injection
      and similarities after p.o. administration were finally confirmed by the
      AUCp.o./AUCi.p. mean ratio which equaled 0.24; 0.79;, 0.54, respectively, as well
      as by different bioavailability data. The results showed that the pharmacokinetic
      bioequivalance between i.v. and p.o. treatment is possible to approach by
      adjustment of fractionated oral dosage.

PMID- 9566049
TI  - Promazine pharmacokinetics during concurrent treatment with tricyclic
      antidepressants.
AB  - The aim of the present study was to search for a possible effect of tricyclic
      antidepressants on the pharmacokinetics of promazine. Male Wistar rats received
      promazine and/or an antidepressant (amitriptyline, imipramine) at a dose of 10
      mg/kg i.p. twice a day for two weeks. Amitriptyline increased the plasma
      concentrations of promazine and N-desmethylpromazine. The concentration of
      promazine sulfoxide was lowered after 30 min, but later it was raised after 6 and
      12 h. The interaction was pronounced after 6 and 12 h when the concentration of
      promazine was 3 times as high, that of N-desmethylpromazine 25 times as high, and
      that of sulfoxide 22 times as high as those observed after administration of
      promazine alone. Similar results were obtained in the brain. Imipramine produced
      less distinct changes in promazine pharmacokinetics. It did not produce any
      significant changes in promazine concentration (a tendency to raise it after 30
      min was observed) in plasma, but it significantly increased the concentration of
      N-desmethylpromazine and decreased that of promazine sulfoxide. Changes in the
      brain did not follow closely those in the plasma. In the brain, significant
      increases in the levels of promazine and its metabolites were observed after 6
      and 12 h. In vitro studies with liver microsomes showed that chronic co
      administration of the antidepressants did not significantly influence the rate of
      promazine demethylation and sulfoxidation. Instead, the Lineweaver-Burk's
      analysis showed that both amitriptyline and imipramine competitively inhibited
      the two metabolic pathways of the neuroleptic. The potency of imipramine to
      inhibit the promazine metabolism in vitro was lower than that of amitriptyline,
      which was in line with its weaker effect on the pharmacokinetics of promazine in
      vivo. The observed increase in the sum of concentrations of the measured
      compounds (promazine + metabolites) in the plasma suggests additional inhibition
      by amitriptyline of another, metabolic pathway of promazine (e.g. hydroxylation).
      It is concluded that amitriptyline and imipramine which interfere with the
      metabolism (and probably distribution) of promazine produce potent increases in
      the brain (in the case of amitriptyline also in the plasma) concentrations of the
      neuroleptic.

PMID- 9566051
TI  - In vitro cytostatic activity of 1,2,4-triazolo- and 1,2,3,4-tetrazolo
      pyridazines.
AB  - Out of a series of fourteen 1,2,4-triazolo(4,3-b)-, and 1,2,3,4-tetrazolo-(1,5
      b)pyridazine derivatives, 4 compounds have been found to reveal high cytostatic
      activity in KB and HeLa human cancer cell lines in vitro with ED50 activity
      values ranging from 0.25 to 3.0 micrograms/cm3 (0.009-0.158 x 10(-4) mole/l), and
      according to DR and D, NCI, NIH Bethesda criterion were qualified for further in
      vivo screening investigation. 6-Chloro-8-(N,N-dimethylaminosulfonylmethyl)
      1,2,3,4-tetrazolo+ ++-(1,5-b)- pyridazine exhibited the strongest in vitro
      cytostatic activity (ED50 = 0.009 x 10(-4) mole/l), comparable with the best
      standards, and higher in comparison with a standard cytosine arabinoside (ED50 =
      0.03-0.04 x 10(-4) mole/l). The presence of chlorine atom at C-6 position in the
      pyridazine ring determines the cytotoxic activity of tetrazolopyridazines as the
      primary factor and C-8 substituents, which influence their better solubility
      seems to be a secondary one, as confirmed by the results of the structure
      activity and solubility-activity relationship analysis. However, for the
      exhibition of the triazolopyridazine activities the presence of two chlorine
      atoms at C-6 and C-3 position was essential.

PMID- 9566052
TI  - Suppressive effect of NMDA receptor antagonist MK-801 on nocturnal serotonin N
      acetyltransferase activity in the rat pineal gland.
AB  - Treatment of rats at night with a non-competitive NMDA receptor antagonist MK-801
      (0.025-1 mg/kg, i.p.) produced a dose-dependent decrease in the nocturnal
      activity of the pineal serotonin N-acetyltransferase (NAT), the rate limiting
      enzyme in melatonin biosynthesis. A maximal inhibition (by 67-75%) of the enzyme
      activity was observed after the drug doses of 0.1 mg/kg in female rats, and 1
      mg/kg in male animals. The data suggest that the NMDA receptor-mediated
      glutamatergic neurotransmission is a step necessary for NAT induction (and
      melatonin biosynthesis) in the mammalian pineal gland.

PMID- 9566053
TI  - Blockade by nifedipine of repeated restraint stress-induced delayed hyperactivity
      in rats.
AB  - Male Wistar rats subjected to repeated restraint stress (1 h per day for 6 days)
      displayed increasing locomotor horizontal and vertical activity, measured for 1 h
      in an autotrack actometer 2 days after the last restraint. The administration of
      L-type Ca2+ channel blocker nifedipine (5 mg/kg i.p.) before each immobilization
      session completely prevented the stress-related augmentation of the locomotor
      activity. This shows that functional Ca2+ channels are required for development
      of stress-related motor activation and suggests that some effects of repeated
      stress may be prevented by application of Ca2+ channel blockade before stressful
      stimuli.

PMID- 9566054
TI  - EMD 57445, the selective sigma receptor ligand, has no effect on the 5
      hydroxytryptamine system.
AB  - The behavioral and biochemical effects of EMD 57445, a selective sigma receptor
      ligand with potential antipsychotic activity, on the 5-hydroxytryptamine (5-HT)
      system were studied in rats and mice. The drug influence was investigated in
      three behavioral tests: 8-OH-DPAT (5-HT1A agonist)-induced behavioral syndrome in
      rats, m-chlorophenylpiperazine (m-CPP, 5-HT1B agonist)-induced hypothermia in
      mice and L-5-hydroxytryptophan (L-5-HTP)-induced head twitches (5-HT2A
      stimulation) in rats. EMD 57445 did not show any activity in all three behavioral
      models. In biochemical studies, no changes in the 5-HT and 5-HIAA levels in rat
      brain cortex, nucleus accumbens, striatum, hypothalamus and hippocampus were
      found. The results indicate that EMD 57445 does not interact with 5-HT (5-HT1A, 5
      HT1B, 5-HT2A) receptor subpopulations and does not affect 5-HT metabolism.

PMID- 9566055
TI  - Influence of imipramine treatment on the group I of metabotropic glutamate
      receptors in CA1 region of hippocampus.
AB  - Effects of repeated imipramine treatment on inositol phosphates accumulation and
      on the reactivity of neurons to metabotropic glutamate receptor (mGlu) agonist
      (1S,3R)-1-carboxycyclopentane-3acetic acid (1S,3R-ACPD) were investigated in the
      rat hippocampal slices. The concentration-dependent increase in inositol
      phosphate accumulation in the slices from CA1 region of hippocampus induced by
      1S,3R-ACPD was not modified by imipramine treatment. 1S,3R-ACPD produced a
      concentration-dependent increase in population spike amplitude recorded in the
      CA1 cell layer. This effect of 1S,3R-ACPD was markedly attenuated by repeated
      imipramine administration. Our results indicate that antidepressant treatment may
      induce a subsensitivity of mGlu receptors in the CA1 region of hippocampus when
      estimated by electrophysiological, but not biochemical measures.

PMID- 9566056
TI  - Carotid angioplasty and stenting. Will they match the gold standard?
AB  - Technological advances in endoluminal equipment have changed treatment strategies
      for vascular disease. While the successful results of intervention in the
      subclavian and innominate arteries are well documented, our experience in the
      carotid arterial region is still in the early stages, and we are mindful of the
      potential for neurologic complications. We now find ourselves in the position of
      comparing the results of endovascular intervention with those of what has become
      a classic, "gold standard" procedure, carotid endarterectomy. Although we have
      yet to determine definitively the superiority of one method over another, it has
      become clear that some carotid lesions are considerably more amenable to
      endovascular treatment than others. We must evaluate the type and location of
      lesions, as well as the technical features of carotid angioplasty and stent
      placement, when we compare the results of endovascular and open procedures.

PMID- 9566057
TI  - Current status of endoluminal grafting for exclusion of abdominal aortic
      aneurysms. The beauty and the beast.
AB  - The exclusion of abdominal aortic aneurysms with endoluminal grafts has generated
      a great deal of interest since the early 1990s, and many centers are currently
      evaluating the procedure and comparing it to classic surgical exclusion. Although
      endoluminal grafting procedures show promise, development and clinical testing of
      devices is a time-consuming process that is influenced greatly by the regulatory
      climate in the country where the clinical trials take place. Nevertheless, a
      number of devices are currently under study, and the advantages of 2nd- and 3rd
      generation technology are reflected in reduced rates of complications such as
      endoleaks and thrombosis. Further study will be required to perfect these devices
      and observe their long-term success in the exclusion of abdominal aortic
      aneurysms.

PMID- 9566058
TI  - Evolution of complete arterial grafting. For coronary artery disease.
AB  - Arterial grafting for the correction of coronary artery disease preceded the use
      of saphenous vein grafts, but the overwhelming popularity of the saphenous vein
      from 1970 to 1985 left the development of arterial grafting dormant. Excellent
      graft patency results from pedicled internal thoracic artery grafting and
      continued saphenous vein graft failure prompted our unit to explore complete
      arterial grafting with internal thoracic artery and radial artery grafts. One
      thousand and fifty-three patients who received a combination of internal thoracic
      artery and radial artery grafts were compared with 1,156 patients who received
      internal thoracic artery and saphenous vein grafts. All patients underwent
      primary coronary artery bypass surgery between 1995 and 1998. The early mortality
      and morbidity and the probability of survival at 2 years were similar in both
      groups of patients. Early graft patency studies of 35 radial artery grafts showed
      33 (94%) were patent at a mean of 12 months. Complete arterial grafting using
      internal thoracic and radial arteries is safe and may provide a long-term
      benefit.

PMID- 9566059
TI  - Transmyocardial laser revascularization. Does it have a role in the treatment of
      ischemic heart disease?
AB  - Transmyocardial laser revascularization, with or without coronary artery bypass
      grafting, is an alternative modality for complete revascularization in selected
      patients with coronary artery disease. Arguably, this modality works by shunting
      left ventricular blood directly into the ischemic myocardium via laser-mediated
      transmural channels. In clinical trials, drilling of laser channels has been
      strongly correlated with long-term improvement of angina, but a causal
      relationship has not yet been documented. For now, the usefulness of
      transmyocardial laser revascularization and the nature of its mechanism remain
      controversial. Some researchers question the existence of myocardial sinusoids
      altogether. Others question the physiologic possibility of moving blood from the
      left ventricular cavity into the myocardium against a pressure gradient. Further
      questions concern the possible routes through which the additional blood gains
      access to the myocardium; the difficulty of objectively documenting improved
      myocardial perfusion after transmyocardial laser revascularization; and the
      nature of the mechanism responsible for the observed clinical benefit. This
      article examines the different aspects of this controversy and discusses the
      current status of transmyocardial laser revascularization, as well as possible
      future directions.

PMID- 9566060
TI  - Prevention of vascular restenosis with radiation.
AB  - Recently, ionizing radiation has been shown to decrease the proliferative
      response to injury in animal models of restenosis. The Scripps Coronary Radiation
      to Inhibit Proliferation Post-Stenting (SCRIPPS) trial was a double-blind,
      placebo-controlled, randomized trial to test this new treatment modality in
      restenotic stented human coronary arteries. Patients with previous restenosis and
      stent implantation were randomized to receive catheter-based radiation with
      Iridium-192 or a placebo using a catheter-based delivery system. Fifty-five
      patients were enrolled; 26 were assigned to Iridium-192 and 29 to the placebo.
      Follow-up angiography was obtained in 96% of patients. Restenosis was observed in
      53.6% of placebo patients compared with only 16.7% of treated patients (P =
      0.025). Late luminal loss was also significantly lower in the Iridium-192 group
      (0.38 +/- 1.06 mm vs 1.03 +/- 0.97 mm, P = 0.009). Clinical outcome also revealed
      a significant reduction in the need for target lesion revascularization in the
      Iridium-192 group (44.8% vs 11.5%, P = 0.008). In this preliminary study,
      catheter-based intracoronary radiotherapy substantially reduced the rate of
      subsequent restenosis. Clinical trials using gamma emitters, beta emitters, and
      beta-emitting radioactive stents are ongoing.

PMID- 9566061
TI  - Atherosclerotic stenosis of the renal arteries. Indications for intervention.
AB  - Advances in the ability to diagnose atherosclerotic stenosis of the renal
      arteries have increased awareness of this disorder over the past decade, and
      several medical specialties have become interested in its pathophysiology,
      diagnosis, and therapy. Improved surgical and anesthetic techniques and the
      development of endovascular technology have paved the way for more aggressive
      management of atherosclerotic renal artery stenosis. However, there is a lack of
      prospective data supporting this aggressive approach, and there is little
      agreement among physician groups concerning the appropriateness of
      revascularization in many patient scenarios. We will examine the available data
      and make recommendations about which patient groups might benefit most from renal
      artery revascularization (surgical or endovascular).

PMID- 9566063
TI  - A novel method for endoluminal treatment of abdominal aortic aneurysms. With bare
      metal Wallstent endoprostheses and endovascular coils.
AB  - The established therapy for symptomatic, expanding abdominal aortic aneurysms is
      open surgical replacement with an artificial graft. Over the last several years,
      there has been increasing enthusiasm for the use of endoluminal graft prostheses
      to exclude abdominal aortic aneurysms. However, even with rapid advances in stent
      graft technology, certain problems (i.e., large profile of the devices, risk of
      thromboembolism, poor flexibility, endoleak formation, and side-branch occlusion)
      have yet to be overcome. We present the case of an 85-year-old woman with
      multiple comorbid illnesses who underwent endoluminal repair of her expanding
      abdominal aortic aneurysms. We used bare-metal Wallstent endoprostheses
      (Schneider, Inc.; Minneapolis, Minn) in combination with endovascular coils
      (Cook, Inc.; Bloomington, Ind). The bare-metal Wallstent endoprostheses were used
      because the patient had severely narrowed iliac arteries and a large side branch
      originating from the aneurysm. The procedure was technically successful, and
      there was no significant morbidity. Follow-up angiographic evaluation at 6 months
      revealed no evidence of vascular enlargement; it also revealed preservation of
      important side branches, and spontaneous thrombosis of the aneurysms.

PMID- 9566062
TI  - Stent revascularization for atherosclerotic renal artery stenosis. 1-year
      clinical follow-up.
AB  - Patients who had undergone stent revascularization of renal artery stenosis for
      poorly controlled hypertension, preservation of renal function, or both were
      monitored to assess the procedure's effect upon subsequent renal function and
      blood pressure control. At 1-year follow-up, systolic and diastolic blood
      pressures had significantly decreased (166 +/- 26 to 156 +/- 25 mmHg and 86 +/-
      14 to 80 +/- 13 mmHg, respectively; P < 0.05), and creatinine levels decreased or
      remained stable in approximately two thirds of the patients. Renal artery stent
      revascularization appears to have a beneficial effect upon blood pressure control
      and a nondeleterious effect upon renal function in the majority of patients.

PMID- 9566064
TI  - Perspectives on the future of platelet glycoprotein IIb/IIIa blockade therapy.
AB  - During the past 2 decades, advances in molecular and cellular biology have
      greatly expanded our understanding of the critical role of platelets in the
      pathogenesis of acute coronary syndromes. This work has suggested that aggressive
      platelet inhibition might reduce cardiovascular morbidity and mortality rates
      beyond the reductions already achieved with aspirin and other conventional
      therapies. Researchers in basic science laboratories have identified a specific
      platelet receptor, the glycoprotein IIb/IIIa integrin, which serves as the
      mediator, or final common pathway, leading to platelet aggregation. This
      glycoprotein receptor is a logical target for the development of antagonists to
      inhibit thrombosis. A number of these antagonists have been tested in clinical
      trials involving coronary intervention, unstable angina, and acute myocardial
      infarction. Herein, I present some of the rationale behind the investigation of
      these agents, as well as some issues to be considered with regard to the future
      of this exciting new class of drugs.

PMID- 9566065
TI  - Cardiac transplantation for pediatric patients. With inoperable congenital heart
      disease.
AB  - Recent studies have reported the expanding use of transplantation as the
      definitive option for pediatric patients with inoperable congenital heart
      disease. This study compares perioperative risk factors and outcomes in pediatric
      patients who received heart transplants for congenital heart disease with those
      in pediatric patients who received heart transplants for cardiomyopathy.
      Retrospective data collected on 40 consecutive pediatric patients undergoing
      cardiac transplantation from 1 January 1990 through 31 January 1995 provided the
      following results: 26 patients with cardiomyopathy (mean age, 7.6 years) and 14
      patients with congenital heart disease (mean age, 7.2 years) underwent heart
      transplantation. Between groups, no significant difference was detected in
      waiting time for a donor heart (cardiomyopathy = 85 days, range = 2 to 409;
      congenital heart disease = 126 days, range = 9 to 396; P = NS); in
      donor/recipient weight ratio (1.27 +/- 0.34 vs 1.27 +/- 0.28, P = NS); or in
      ischemic times (209 +/- 92 minutes vs 248 +/- 70 minutes, P = NS).
      Cardiopulmonary bypass times accounted for the only significant difference (73 +/
      21 minutes vs 102 +/- 29 minutes, P = 0.003). No significant difference was
      found in the number of infection episodes, total days hospitalized, rejection
      episodes, or incidence of transplant coronary artery disease. Forty-month
      actuarial survival was 88% +/- 6% and 92% +/- 7% for cardiomyopathy and
      congenital heart disease transplant recipients, respectively (P = NS). We
      conclude that post-transplantation morbidity and mortality in patients with
      previous congenital heart disease are not significantly different from morbidity
      and mortality in patients with cardiomyopathy. Transplantation should be
      considered an acceptable therapeutic option for patients with congenital heart
      disease when surgical repair of the native heart is not possible.

PMID- 9566066
TI  - Stanford type A aortic dissection. A new surgical approach.
AB  - We describe a new surgical technique adopted for the repair of Stanford type A
      aortic dissection. In order to minimize the risk of malperfusion caused by
      retrograde flow during cardiopulmonary bypass, we avoid femoral artery
      cannulation. On the hypothesis that it is best not to interfere with the
      hemodynamics of the dissection, we cannulate the dissected ascending aorta, in
      either the true or false lumen. We here report 2 cases of successful surgical
      treatment of Stanford type A aortic dissection. In both cases, the false lumen
      was cannulated under deep hypothermic circulatory arrest, without clamping the
      aorta. While the patient was cooling, a 10-mm GORE-TEX side arm was sutured to a
      Dacron graft prosthesis. Repair of the aortic arch was carried out 1st. The
      aortic cannula was inserted into the GORE-TEX side arm, the tubular prosthesis
      was cross-clamped, and cardiopulmonary bypass was reinstituted. After this, the
      aortic bulb was repaired as usual and the tubular prosthesis was sutured to the
      bulb. No postoperative cerebral complication occurred. Our experience must be
      confirmed by more cases and a longer follow up.

PMID- 9566067
TI  - Management of annuloaortic ectasia in association with aortic regurgitation.
AB  - Annuloaortic ectasia associated with severe aortic regurgitation is usually
      managed by implanting a composite graft that comprises both valve and conduit.
      Synthetic valved conduits have been used by most cardiovascular surgeons, with
      various modifications in the technique. Yet prosthetic valves carry the risks
      associated with anticoagulation therapy, together with an increased risk of
      infective endocarditis. We report a case in which a cryopreserved aortic
      homograft was used for a Bentall procedure in a patient who had annuloaortic
      ectasia with severe aortic regurgitation. To the best of our knowledge, there are
      no prior published reports of homograft insertion in treatment of annuloaortic
      ectasia.

PMID- 9566068
TI  - Aortopulmonary artery fistula. Presenting with congestive heart failure in a
      patient with aortic dissection.
AB  - Although it is a rare occurrence, aortic dissections can rupture into the cardiac
      chambers or great vessels. A review of the English literature revealed only 3
      cases of fistula between an aortic false lumen and the main pulmonary artery that
      were repaired successfully. In this article, we report the case of a chronic type
      I aortic dissection with an aortopulmonary artery fistula. The patient presented
      with congestive heart failure. One year earlier he had undergone aortic valve
      replacement. To our knowledge, this is the 4th case of a successfully repaired
      type I aortic dissection with rupture into the pulmonary artery and the 1st such
      case involving a patient who had undergone a previous cardiac operation.

PMID- 9566069
TI  - Successful surgical treatment of visceral artery aneurysms. After failure of
      percutaneous treatment.
AB  - We report 2 cases involving aneurysms of visceral arteries that needed surgical
      treatment after unsuccessful percutaneous treatment. In the 1st case, repeated
      embolizations with Gianturco coils and angiographic guidewires had failed to
      obliterate a large aneurysm of the hepatic artery. In the 2nd case, a
      peripancreatic pseudoaneurysm caused recurrent gastrointestinal bleeding despite
      embolization with Gianturco coils. In both patients, left medial rotation of the
      viscera provided access to the origin of the affected artery at the aorta,
      enabling the surgeon to control bleeding before opening the aneurysm. The
      advantages and limitations of the most commonly performed percutaneous procedures
      are discussed, as are the surgical options.

PMID- 9566070
TI  - Balloon pulmonary valvuloplasty and stent implantation. For peripheral pulmonary
      artery stenosis in Alagille syndrome.
AB  - We report the case of a patient with Alagille syndrome and severe pulmonary valve
      and bilateral pulmonary artery branch stenosis. In this patient, transcatheter
      balloon pulmonary valvuloplasty combined with bilateral pulmonary artery
      angioplasty and stent placement provided excellent immediate results and long
      term improvement.

PMID- 9566071
TI  - Cardiac hemangioma. A case report and discussion.
AB  - A cardiac hemangioma is a rare form of primary cardiac tumor. To our knowledge,
      only 34 cases of cardiac hemangioma have been discussed in the literature at the
      time of this writing. We report the case of a patient who presented with 1
      episode of exertional dyspnea. The medical history, physical exam, work-up,
      surgical approach, and outcome are discussed. Other published reports on this
      topic are also reviewed.

PMID- 9566072
TI  - False aneurysm of the right internal mammary artery. Late rupture after
      sternotomy.
AB  - This report describes a late, near-fatal rupture of a false aneurysm of the right
      internal mammary artery subsequent to coronary artery bypass grafting. The
      patient presented to us in shock due to hemorrhaging, 8 weeks after bypass
      surgery that had been complicated by sternal fracture, dehiscence, and infection.
      Emergent thoracotomy and suture ligation controlled the hemorrhage. To the best
      of our knowledge, this is the 1st reported case of late massive hemorrhage caused
      by injury to an internal mammary artery after sternotomy. The literature is
      reviewed and discussed.

PMID- 9566073
TI  - Preocclusive thrombosis of an internal carotid artery.

PMID- 9566074
TI  - Persistent left superior vena cava discovered during placement of central venous
      catheter.

PMID- 9566075
TI  - Blood, drugs, and the United States Pharmacopeia.

PMID- 9566076
TI  - Hepatitis C lookback.

PMID- 9566077
TI  - GBV-C/HGV: a new virus within the Flaviviridae and its clinical implications.

PMID- 9566079
TI  - Hemophilia management. United States Pharmacopeial Convention, Inc.

PMID- 9566078
TI  - Surveillance of blood transfusion safety: contribution of the hemovigilance
      strategy in France.

PMID- 9566080
TI  - Platelet storage variables and in vivo characteristics.

PMID- 9566081
TI  - Physiologic and perceptual responses to hypercarbia during warm- and cold-water
      immersion.
AB  - Thermoregulatory, respiratory, and perceptual responses to acute CO2 exposure
      during light exercise (75 W) were assessed in 12 U.S. Navy divers clad only in
      swim trunks while immersed to the neck in water at 18 degrees and 34 degrees C.
      The CO2 exposures consisted of a linear 10-min ramp increase in the inspired
      fraction of CO2 (FICO2) from 0 to 6% followed by 5 min of breathing 6% CO2. The
      ability to detect and rate the severity of hypercarbia, as well as subjective
      changes in thermal comfort, were assessed by comparing subjective ratings given
      during the CO2 exposures with those given during immersion trials where the FICO2
      was maintained at 0%. Hypercarbia was recognized earlier and, at a given PETCO2,
      was perceived to be greater during cold- than during warm-water immersions (P <
      0.01). The CO2 exposures did not affect the thermal balance of divers as assessed
      by changes in heat flux and rectal temperature. However, increased feelings of
      warmth were reported during both the cold and warm immersions when breathing
      raised concentrations of CO2 (P < 0.01). During the cold immersions, acute
      exposure to 6% CO2 significantly decreased forearm blood flow (P < 0.05), but did
      not affect finger blood flow. It is concluded that PETCO2 levels can reach
      unacceptably high concentrations (> 60 mmHg) before hypercarbia can be reliably
      detected by working divers. Furthermore, the ability to detect hypercarbia is
      poorer when immersed in warm water than when in cold water.

PMID- 9566082
TI  - Diving response and apneic time in humans.
AB  - The aim of this study was to compare apneic time with the human diving response,
      defined as heart rate (HR) reduction and reduced skin blood flow, in groups with
      varying degrees of breath-hold diving experience. Apneic time and HR reduction at
      apneas in air and apneas with face immersion in cold water were thus recorded in
      nine groups. Skin capillary blood flow was recorded in six of the groups. All
      subjects received the same information on maximizing apneic duration, and no
      information about their progress during the apneas. The longest apneas and the
      most pronounced cardiovascular adjustments were found in the young, trained
      divers. It was found that apneic time was significantly correlated to HR
      reduction among the nine groups (r = 0.94, P < 0.001), and to skin capillary
      blood flow reduction among the six groups where the parameter was measured (r =
      0.82, P < 0.05). The correlation between HR reduction and skin capillary blood
      flow reduction was also significant (r = 0.85, P < 0.05). When the difference in
      HR reduction and apneic time between apneas in air and apneas with face immersion
      were compared in the nine groups, it was found that all groups reacted with a
      more pronounced HR reduction during apneas with face immersion. All groups
      without prior breath-hold diving experience were found to perform shorter apneas
      with face immersion than apneas in air, or apneas of the same duration in both
      conditions, which has been reported in other studies. However, in all groups with
      diving experience, the apneic time was prolonged during apneas with face
      immersion. The results of this study suggest an oxygen-conserving effect of the
      diving response in trained apneic divers.

PMID- 9566083
TI  - Arterial oxygen desaturation during apnea in humans.
AB  - We studied the effect of the human diving response, defined as bradycardia and
      reduced peripheral blood flow, on arterial hemoglobin desaturation. We induced a
      diving response of different magnitudes by using apnea in air and apnea with face
      immersion. Each of 21 subjects performed five apneas in air and five apneas with
      face immersion in 10 degrees C water. Periods of apnea in both conditions were of
      the same duration in any individual subject (average: 126.4 s) and the order of
      air and water was equally distributed among subjects. Heart rate, skin capillary
      blood flow, arterial blood pressure, arterial hemoglobin oxygen saturation during
      apneas, and end-tidal fractions of CO2 after apneas were recorded with non
      invasive methods. The bradycardia and capillary blood flow reduction during apnea
      in air (7.8 and 37.7% change from control, respectively) were significantly
      potentiated by face immersion (13.6 and 55.9%, respectively). Arterial hemoglobin
      desaturated more during apnea in air (2.7%) compared to during apnea with face
      immersion (1.4%). We conclude that the potentiation of the human diving response
      with face immersion in cold water leads to a smaller decrease in arterial
      hemoglobin saturation, which may reflect an oxygen-conserving effect.

PMID- 9566084
TI  - Pattern shift visual evoked potential screening for HBO2 in mild-to-moderate
      carbon monoxide poisoning.
AB  - Pattern shift visual evoked potential (PSVEP) N75 and P100 latencies were
      evaluated as an objective, widely available and rapid test of brain dysfunction
      in a group of 11 patients in the acute phase (first 6 h) of mild-to-moderate
      carbon monoxide (CO) poisoning. N75 and P100 latency results were compared to
      nearly simultaneously obtained standard CO Neuropsychological Screening Battery
      (CONSB). Patients were sought in whom treatment decisions concerning hyperbaric
      oxygen (HBO2) vs. normobaric oxygen (NBO2) might be difficult, and were excluded
      from the study if confounding variables existed for CONSB or PSVEP. N75 and P100
      latencies were also obtained after completion of NBO2 or HBO2 therapies. Only one
      patient, judged clinically to have the mildest poisoning in the series, had
      significantly abnormal initial PSVEP latencies. This patient's simultaneous CONSB
      was normal and the abnormal PSVEP latencies failed to normalize post treatment
      with NBO2. PSVEP latencies were not found to be a sensitive screening tool for
      treatment decision making in a group of acutely CO poisoned patients where
      treatment decisions might be difficult.

PMID- 9566085
TI  - Toxicity of hyperoxia and high pressure on C3H/10T1/2 cells and effects on
      cellular glutathione.
AB  - Saturation diving involves the exposure of humans to elevated partial pressure of
      oxygen (PO2) and high ambient pressure. The present study is part of a research
      program that focuses on how such conditions affect basal cellular functions.
      C3H/10T1/2 Cl 8 mouse embryo fibroblasts were exposed to 20-80 kPa O2 in a He-O2
      mixture at 0.1 and 5.0 MPa ambient pressure for 24-72 h. Elevated PO2 had severe
      toxic effects on the cells, and there was an additional effect of high pressure
      on net cell growth. A persistent reduction of cell growth rate after the end of
      exposure to He-O2 was noted, suggesting genetic effects. We observed no effects
      of the ambient pressure per se in this respect. High PO2 increased the cellular
      glutathione level reaching a plateau approximately 100% above control at a PO2 of
      60 kPa. No alteration of the glutathione redox status was observed, and high
      ambient pressure per se had no significant effect on the cellular glutathione
      content. The increased glutathione content did not completely protect the cells
      against toxic injury of high oxygen levels.

PMID- 9566086
TI  - Computer simulation of microscopic cerebral air emboli absorption during cardiac
      surgery.
AB  - Microscopic cerebral arterial air emboli (MCAAE) cause neurologic injury during
      cardiac surgery. We used a mathematical model of gas absorption to gain a
      preliminary assessment of what physical or physiologic parameters affect MCAAE
      absorption in the setting of cardiac surgery with its unique set of normal
      values. Simulated MCAAE of radii 50 and 200 microns have absorption times of 2
      and 32 min, respectively. Predicted absorption times depend dramatically on PaN2.
      MCAAE are predicted to be absorbed twice as quickly at a PaN2 of 0 vs. 380 mmHg
      (FiO2 approximately equal to 0.50). Moderate hypothermia (27 degrees C) is
      predicted to cause only small decreases in absorption time. Changes in cerebral
      blood flow (for example, as affected by hemoglobin concentration, PaCO2, PaO2,
      collateral circulation, anesthetics, or cerebral metabolism) probably have only
      small effects on absorption time. Intravascular perfluorocarbons are predicted to
      cause small-to-moderate decreases in absorption time. In conclusion, there is
      probably only one important determinant of MCAAE absorption time during
      normothermic or moderately hypothermic CPB: arterial nitrogen partial pressure.

PMID- 9566088
TI  - Does cold water truly promote diver's ear?
AB  - Ninety-seven Japanese military divers from two districts, Mutsu (Northern Japan)
      and Yokosuka (Central Japan), were examined for the incidence of diver's ear
      (exostosis of the external auditory canal). The average temperature of sea water
      of the two districts is different because of their latitude, but the two groups
      had no significant difference in diving career. The incidence of exostosis in the
      Mutsu (cold area) group showed a significant increase as the diving career
      progressed. This tendency was not seen in the Yokosuka (warm area) group. The
      severity of exostosis increased in divers in both districts. The incidence of
      exostosis in Mutsu was significantly higher than in Yokosuka. The Mutsu group
      also showed a higher ratio of exostosis grade 2 than the Yokosuka group. These
      results may support the hypothesis that cold water facilitates formation of
      external auditory canal exostosis.

PMID- 9566087
TI  - Evaluation of oxygen and pressure in treatment of decompression sickness in
      guinea pigs.
AB  - These experiments examined whether increasing the partial pressure of oxygen
      (PO2), hydrostatic pressure, or both were responsible for the improvement in
      effectiveness of recompression treatment previously observed in guinea pigs with
      increasing depths of air. Unanesthetized male guinea pigs (600-700 g) were
      subjected to 8.6 atm abs (871 kPa) air dives for 60 min and then decompressed at
      1.82 atm (184 kPa)/min to the surface. Subsequently, animals usually displayed
      hypotension, cardiac arrhythmia, and tachypnea, indicative of a fatal bout (> 95%
      death rate) of decompression sickness (DCS). Animals that developed DCS were
      treated by recompressing to depths ranging from 2.5 to 11.6 atm abs (253-1175
      kPa), with 14, 28, 42, or 100% O2/balance N2. This design produced PO2's at
      treatment depth ranging from 0.4 to 3.6 atm abs (41-365 kPa). Upon recompression,
      recovery of blood pressure, heart rate, and breathing rate generally occurred.
      The area under the breathing rate vs. time curve was used to examine the
      effectiveness of treatment over a period of 60 min. A dramatic improvement in
      recovery over time was observed with increasing recompression depth for all gas
      mixtures. Analysis indicated that the positive response to depth was related to
      increasing hydrostatic pressure, increasing PO2 had no statistically significant
      beneficial effect.

PMID- 9566089
TI  - Changes in antibody titres against Leishmania infantum in naturally infected dogs
      in southern Spain.
AB  - Monthly serological follow-up of the antibody titres against Leishmania infantum
      in hunting dogs in rural southern Spain was carried out during the transmission
      period (from April to October in 1996). Titres > or = 160 were regarded as
      indicating disease, while lower positive tires were also recorded as
      'seropositive'. Over this period, a significant (p < 0.05) increase in the
      percentage of dogs with a titre > or = 160 was observed; from 12.6% in April to
      19.2% in October. The same pattern was observed with the seropositives (titre >
      or = 20) which increased from 36.3% in April to 55.6% in October. Of
      seronegatives in April, 60% were still negative in October whereas 22% had a
      titre of 20-40 and 18% had a titre > or = 80. Similarly, 68% of those with a
      titre > or = 80 in April still had a titre in this range in October, 25% of the
      titre had decreased to 20-40 and in 7% to a zero titre. The most noteworthy is
      that 25% of animals reached titres of > or = 80 and decreased to zero or 20 more
      than once. Parallel to this study, another survey was conducted on dogs from
      Granada city centre. The seroprevalences (titres > or = 160) at the start and the
      end of the transmission period were 1.7 and 3.7% respectively and the
      seropositively values were 12 and 11% respectively.

PMID- 9566090
TI  - Serum immune response to Giardia duodenalis in experimentally infected lambs.
AB  - Twenty-three protozoan-free lambs were experimentally infected with Giardia
      duodenalis trophozoites at 6 weeks of age, while 24 controls lambs were not
      challenged. Weekly blood samples were taken and faecal cyst counts monitored for
      11 weeks following infection. All experimentally infected lambs remained infected
      throughout the 11 week study period and control animals remained free of the
      parasite. Giardia-specific serum IgM, IgG and IgA antibody titers were determined
      weekly in 10 infected and 10 control lambs by enzyme-linked-immunosorbent assay
      (ELISA). Western blot analysis of serum immunoglobulins to proteins derived from
      four different Giardia isolates (S2, WB, D3 and NF) was performed. Weekly mean
      control IgM, IgG and IgA titers did not change throughout the study. Infected
      lambs showed no difference in IgM titers between weeks 0 and 11, but IgG and IgA
      titers of infected lambs differed from the preimmune (week 0) serum titer at
      weeks 5, 7, 9, 11 and weeks 5, 9 and 11 respectively. SDS polyacrylamide gel
      electrophoresis analysis showed homogeneity in the proteins of the four Giardia
      isolates. Antigenic proteins were also similar for all four isolates; however,
      the proteins recognized by IgM, IgG and IgA antibodies differed. The weak immune
      response of lambs to Giardia may account for the chronic nature of this disease
      in sheep.

PMID- 9566091
TI  - Ultrastructural morphology of sarcosporidiosis in alpine ibex (Capra ibex).
AB  - The authors describe the ultrastructural morphology of the cyst wall of
      sarcocysts in the muscles from Ibex, found dead and sent to this department to be
      examined. Several samples of the diaphragm were taken from 52 Ibex of different
      age and sex, one Hispanic and the others from the Gran Paradiso National Park
      (GPNP). The samples were prepared for electron microscopy after testing for
      sarcocystiosis through extemporaneous microscopic examination. Eighty-six percent
      were positive. The morphology of the cyst wall led to the identification of three
      types of sarcocysts in the Ibex of the GPNP and a further type in the Hispanic
      one. The morphology of the sarcocysts wall is similar to the wall of the species
      described in the domestic ruminants from several authors.

PMID- 9566092
TI  - Pharmacokinetics of meglumine antimoniate after administration of a multiple dose
      in dogs experimentally infected with Leishmania infantum.
AB  - Pharmacokinetics of meglumine antimoniate in dogs with experimentally induced
      leishmaniosis has been investigated. After infection, dogs received a dose of 75
      mg kg-1 of meglumine antimoniate twice daily by subcutaneous injection for 10
      days. Blood samples were collected throughout the treatment. No statistical
      differences were found in the kinetic behaviour of the drug administered as a
      single dose to healthy dogs and that administered as a multiple dose to infected
      animals. However, peak plasma concentrations (Cmax) of 30.8 +/- 12.8 micrograms
      ml-1 found after this dosage regimen were higher than those observed after the
      single dose administration of 100 mg kg-1 24 h-1. Furthermore, sustained antimony
      concentrations of 1.14 +/- 0.52 micrograms Sb ml-1 were detected throughout the
      treatment. No signs of toxicity were found in the animals treated indicating that
      this regimen would be very appropriate to treat canine leishmaniosis.

PMID- 9566093
TI  - Nucleotide sequence heterogeneity in the small subunit ribosomal RNA gene
      variable (V4) region among and within geographic isolates of Theileria from
      cattle, elk and white-tailed deer.
AB  - The phylogenetic relationships among fourteen isolates of benign Theileria spp.
      infecting cattle, elk and white-tailed deer were studied by nucleotide sequence
      comparisons of the variable (V4) region (200 nucleotides) of the small subunit
      ribosomal RNA gene. Included were six Korean bovine, one Japanese bovine, three
      North American bovine, and four North American cervine isolates. The SSU rRNA
      gene from each isolate was amplified, cloned, and the V4 region fragment
      sequenced. Seven different nucleotide sequence patterns were obtained and
      classified. Type A was identical to T. buffeli SSU rRNA gene sequence (GenBank
      Accession No. Z15106) and was found in Korean, Japanese, and North American
      bovine isolates. Type B was found in bovine isolates from Korea, Japan and North
      America. Type C was found only in the Korean bovine isolate from Chungnam. Type D
      was found in a Korean and in a North American bovine isolate. Type E was found in
      a bovine isolate from Cheju Island of Korea and a North American cervine (elk)
      isolate. Types F and G were found only in North American cervine isolates (both
      white-tailed deer and elk) and appear to represent a species separate from the
      bovine isolates. The presence of several sequence types observed in most of the
      bovine Theileria isolates may indicate mixed species (or subspecies) populations
      and/or multiple genotypes within a single species.

PMID- 9566094
TI  - Prevalence of antibodies to Neospora caninum and Toxoplasma gondii in cattle and
      water buffaloes in southern Vietnam.
AB  - Serum samples from 200 dairy cattle and 200 beef water buffaloes were collected
      in southern Vietnam during May to September 1995. The sera were analysed for
      antibodies to Neospora caninum by an enzyme-linked immunosorbent assay and the
      indirect fluorescent antibody test, and for antibodies to Toxoplasma gondii by
      the direct agglutination test. Significant levels of N. caninum antibodies were
      detected in 5.5% of the cattle sera and in 1.5% of the water buffalo sera. 10.5%
      of the cattle sera and 3% of the water buffalo sera were found to contain T.
      gondii antibodies. Two of the cattle sera had both T. gondii and N. caninum
      antibodies. The present communication is the first to report serological evidence
      of N. caninum infection in the water buffalo.

PMID- 9566095
TI  - Distribution, prevalence and intensity of Schistosoma bovis infection in cattle
      in Iringa district, Tanzania.
AB  - Monthly abattoir, farms and village surveys were carried out to determine the
      distribution, prevalence and intensity of Schistosoma bovis infection in cattle
      in Iringa district in the southern highlands of Tanzania between August 1991 to
      August 1992. Abattoir surveys were conducted at the Iringa regional abattoir and
      age, sex, live animal grade and livestock market of origin of each of 342 animals
      examined were recorded. Five grams of the central part of the jejunum were
      collected from each animal and schistosome egg counting was carried out after
      tissue digestion. Nine farms and six villages were randomly selected and age, sex
      and origin of 501 cattle was recorded. Faecal samples were collected from each
      animal and quantification of schistosome eggs was carried out by means of the
      Modified Bell filtration technique. Abattoir surveys revealed S. bovis to be
      present in 116 out of 342 cattle examined in 10 out of the 12 livestock markets
      surveyed giving a point prevalence of 34%. A high frequency (70.1%) of low tissue
      egg counts (< 200 eggs per gram) was observed among the infected animals. The
      prevalence and intensities of infection observed in the slaughtered cattle were
      not related to the age-group, sex and grade of the animals. Results from faecal
      egg counts in nine farms and six villages disclosed that the infection was
      predominant in four farms (Lulanzi, Igumbiro, Ruaha and Mlolo) and three villages
      (Itunundu, Ibumu and Lulanzi). Egg counts per gram of faeces (EPGF) at Lulanzi
      dairy farm revealed a peak egg excretion in 1-3 yr old animals which was followed
      by a decline in the number of EPGF within the age group of 3- to 9-yr old
      animals. However, the faecal egg excretion tended to rise again in animals over 9
      years old. Deaths of four animals which were preceded by signs of intermittent
      diarrhea, loss of condition, anaemia and high faecal egg counts was observed at
      Lulanzi farm. Postmortem examination of the dead animals revealed that they had
      severe schistosomal lesions and higher tissue egg counts than the slaughtered
      cattle. It was concluded from the present study that S. bovis infection in cattle
      is very common in foci in Iringa district and possibly the whole of the southern
      highlands of Tanzania and in some enzootic farms it could be among the major
      causes of ill-health and lowered productivity.

PMID- 9566097
TI  - Prevalence of Dirofilaria immitis in cats in Japan.
AB  - The prevalence of Dirofilaria immitis in cats in Japan has been examined since
      1957. Twenty surveys involving a total of 3775 cats, conducted in two islands of
      Japan (Honshu and Kyushu), were studied. The surveys evaluated both stray (3617)
      and house (158) cats. Presence of D. immitis was detected at necropsy. The
      results show a prevalence of D. immitis varying from 0.5 to 9.5% for stray cats
      and from 3.0 to 5.2% for house cats on the two islands.

PMID- 9566098
TI  - [Rheumatology in Switzerland].

PMID- 9566096
TI  - Epidemiology of Anoplocephala perfoliata infection in foals on a stud farm in
      south-western Sweden.
AB  - The egg output and humoral antibody response to scolex antigens of the equine
      tapeworm Anoplocephala perfoliata were monitored in naturally infected foals by
      an egg flotation/centrifugation method and an indirect enzyme-linked
      immunosorbent assay (ELISA). The study was performed on a stud farm in south
      western Sweden between May 1994 and April 1995. Sequential blood and faecal
      samples were taken from 21 foals during their first summer on pasture and until
      tapeworm eggs were detected. Results were expressed separately for 10 and 11
      foals born before and after the end of April 1994, respectively. Increased levels
      of antibodies were noticed from October and onwards in both groups whereas
      tapeworm eggs were detected in the faeces of all foals about 4 months later. The
      antibody response was similar in both groups but it was more pronounced in foals
      born before April 1994. All foals were treated in March 1995 with an oral paste
      formulation of pyrantel pamoate at a dose rate of 38 mg/kg bodyweight. Most
      animals responded to the anthelmintic treatment and one month later, tapeworm
      eggs were only detected in one out of the 18 foals examined one month after
      treatment. Thus, the treatment reduced the number of A. perfoliata egg positive
      horses by 94%. A concomitant decline in antibody levels was also observed.
      Western immunoblot analysis of sequential individual serum samples showed that at
      least 10 different scolex antigens in the molecular weight range 10-200 kDa were
      recognised. Banding intensities, especially of the 10 kDa, 45 kDa and 66 kDa
      proteins were different in the sequential sera taken during the course of
      infection.

PMID- 9566099
TI  - [Measuring knee joint kinesthesis for determining proprioceptive deficits in
      varus gonarthrosis].
AB  - Studying knee osteoarthrosis proprioceptive deficits play a growing role.
      However, the methods for the detection of these deficits using joint position
      sense measurements have been criticized recently. Therefore, we developed a new
      method for the measurement of knee-joint kinaesthesia. At 5 different angular
      velocities of passive knee movement both movement and stop detection were tested.
      Tests were performed both in 25 patients with osteoarthrosis of the knee and in a
      control group of 20 age related normal subjects. In addition to the measurements
      of movement detection and stop-detection thresholds, a specific detection-failure
      analysis was performed in our study. In addition to a significant improvement of
      proprioceptive abilities with increasing angular velocities, detection failure
      analysis brought about significant differences between patients with knee
      osteoarthrosis and normal subjects yielding a significant proprioceptive deficit
      in osteoarthrosis of the knee. In contrast, in case of correct movement detection
      or stop-detection there were no significant differences in the detection
      threshold values between normal and ostheoarthrotic knees. In conclusion, both
      the lack of differences in detection thresholds between the arthrosis and the
      control-groups and the increased detection failure rates in arthrosis patients
      gave evidence for these proprioceptive differences being a result of central
      nervous dysregulation in knee osteoarthrosis.

PMID- 9566100
TI  - [Is H15 (resin extract of Boswellia serrata, "incense") a useful supplement to
      established drug therapy of chronic polyarthritis? Results of a double-blind
      pilot study].
AB  - BACKGROUND: Leukotrienes and prostaglandines are important mediators of
      inflammation. While prostaglandine synthesis can be influenced by NSAIDs
      therapeutical approaches to the 5-lipoxygenase pathway are rare. Resinous
      extracts of Boswellia serrata (H15, indish incense), known from traditional
      ayurvedic medicine, decrease leukotriene synthesis in vitro. Case reports suggest
      a clinical role for that drug. METHODS: Outpatients with active RA have been
      enrolled into a multicenter controlled trial. Patients received 9 tablets of
      active drug (3600 mg) or placebo daily in addition to their previous therapy.
      Doses of NSAIDs could be adjusted on demand. Efficacy parameters, Ritchies Index
      for swelling and pain, ESR, CRP, pain on VAS and NSAID dose were documented at
      baseline and 6 and 12 weeks after initiation. Mean values and medians were
      calculated to compare the groups for significant or clinically relevant change
      from baseline or difference between both groups at any time point of observation.
      RESULTS: A total of 78 patients were recruited in 4 centers, the data have been
      published in abstract form. Only 37 patients (verum 18, placebo 19), enrolled in
      Ratingen were available for detailed efficacy and safety analysis. All
      evaluations in these patients were performed by one investigator (G.H.). There
      was no subjective, clinical or laboratory parameter showing a significant or
      clinically relevant change from baseline or difference between both groups at any
      time point of observation. The mean NSAID dose reduction reached levels of 5.8%
      (H15) and 3.1% (placebo). One patient in each group showed a good response in all
      parameters but 4 patients in each group worsened. The others showed no alteration
      of their disease. CONCLUSION: Treatment with H15 showed no measurable efficacy.
      Controlled studies including a greater patient population are necessary to
      confirm or reject our results.

PMID- 9566101
TI  - [Introducing "combination therapy"].

PMID- 9566102
TI  - Clinical pharmacology of combination disease-controlling (DCART/DMARD) therapy in
      rheumatoid arthritis.

PMID- 9566103
TI  - [Basic therapeutic combination therapy in chronic polyarthritis: an overview].
AB  - Therapy of rheumatoid arthritis with a combination of several disease-modifying
      drugs aims towards better control of the disease than achievable by monotherapy.
      Based on a broad variety of clinical studies, revealing more or less positive
      results, several combinations have been suggested: the inclusion of cyclosporin
      into combinations with methotrexate, the inclusion of sulfasalazine into
      combinations with methotrexate, the combined use of two chemotherapeutic
      substances, including methotrexate, azathioprine and cyclophosphamide, the
      inclusion of chloroquine derivatives into such or other combinations, and the
      combination of methotrexate with injectable gold. The validity of some of the
      studies is affected by high drop out rates and by the unknown influence of
      concomitant therapy with corticosteroids. Our own beneficial experience with the
      triple combination of methotrexate with azathioprine and chloroquine in 21
      patients with refractory rheumatoid arthritis is summarized.

PMID- 9566104
TI  - Combination of sulphasalazine and methotrexate in the treatment of rheumatoid
      arthritis.

PMID- 9566105
TI  - Combination therapy for rheumatoid arthritis with methotrexate and cyclosporine.

PMID- 9566106
TI  - [Long-term combination therapy of chronic polyarthritis: methotrexate and
      parenteral gold].

PMID- 9566107
TI  - Future use of biologic agents alone and in combination for the treatment of
      rheumatoid arthritis.

PMID- 9566108
TI  - Limitations of randomized controlled clinical trials to depict accurately long
      term outcomes in rheumatoid arthritis.

PMID- 9566109
TI  - [Concomitant manifestation of ochronosis and chronic polyarthritis in a patient].
AB  - Ochronosis is rare disorder of tyrosin catabolism with an autosomal, recessive
      trait. Clinical signs predominantly affect the locomotor system. Inflammatory
      episodes in large joints can mimick Rheumatoid Arthritis (RA). Brownish
      discoloration of sclerae and cartilage is characteristic, diagnosis is confirmed
      by typical changes of spinal X-rays and the findings of homogentisic acid in
      urine samples. We describe a case of a 53 year old female patient with ochronosis
      and a second diagnosis of RA.

PMID- 9566110
TI  - Unfinished business: the asbestos textiles mystery.

PMID- 9566111
TI  - Dust exposure and lung cancer in Quebec chrysotile miners and millers.
AB  - A large cohort of men born between 1891 and 1920 and employed for at least a
      month in the chrysotile producing industry of Quebec has been under study since
      1966. These men were followed from first employment (the earliest in 1904) to
      1992, by which time over 8000 had died, 657 from lung cancer. The current study
      is of 488 cases of lung cancer formerly employed at three places, viz. a major
      complex, here called Company 3, in the region of Thetford Mines (243 cases), the
      mine and mill in the town of Asbestos (206) and a small asbestos-products factory
      in the same town (39). For each case, four referents were sought by random
      selection from among survivors to a greater age, after matching on place of
      employment, age of starting work, smoking habit and date of birth. This process
      was highly successful, although six cases had less than four referents. For each
      man (the 488 cases with 1941 referents) and for each calendar year of employment,
      we obtained the fraction of the year worked at various levels of intensity,
      assessed in 13 'dust categories' of mpcf (million particles per cubic foot). We
      then calculated how many years each man spent at these various levels; these
      years, adjusted for the length of the working week (66 h until 1937; 48 h 1938
      1949; and 40 h 1950-1985), were accumulated up to ten years before the death of
      the case. The men were classified according as they were non- or ex-smokers, or
      smokers, of cigarettes. For each man at Company 3 and one referent for each, his
      years of work in a central area of five mines and in a peripheral area of ten
      mines were differentiated; contamination of the chrysotile by fibrous tremolite
      was known to be much greater in the central than in the peripheral area. Case
      referent comparisons, within place of employment, were made by conditional
      logistic regression. As anticipated from earlier subject-years analyses, lung
      cancer risks were found to be negligible for years worked in dust categories 1
      and 2 (averaging 0.5 and 2 mpcf), regardless of place; as the upper limit of
      category 1 is considerably higher than permitted nowadays, the lung cancer risk
      from exposure to chrysotile at permitted levels can be taken as extremely small.
      Patterns of exposure-response for higher categories were irregular. At Company 3,
      some risks appeared elevated for years spent in the higher dust categories: 3-4,
      5-7, 8-10 and 11-13, with averages around 9, 20, 36 and 92 mpcf, respectively.
      For categories 3-4 and 8-10, the odds ratios were high for some or all work in
      the central area, but minimal for years spent in the peripheral area only. Odds
      ratios were fairly low for cigarette smokers who worked in categories 5-7 and
      also for years spent in the highest categories (11-13). At the mine and mill in
      Asbestos, all risks were low except for years worked by non- and ex-smokers in
      categories 7-13 (ca. 40 mpcf). There were no increased risks at the factory. It
      was known from the subject-years analyses that most of the excess had occurred at
      Company 3, but it is now clear that for all practical purposes it was confined to
      the central area there, probably due largely to fibrous tremolite and in dust
      conditions of at least dust category 3. The average of this category was 7 mpcf
      or very roughly 24 fibres/ml, about two orders of magnitude higher than today's
      hygiene standards.

PMID- 9566112
TI  - A comparison of historic asbestos measurements using a thermal precipitator with
      the membrane filter-phase contrast microscopy method.
AB  - The published results and analytical methods used in a 1938 survey of the
      spinning area in a UK crocidolite asbestos factory have been described and re
      interpreted, by comparing the method used with the current membrane filter-phase
      contrast microscopy (MF-PCM) method for asbestos. By good fortune, most of the
      original microscope, and thermal precipitator sampling heads similar to those
      used for sampling were available, as well as guidance from the factory inspector
      who collected and analysed the original samples. A textile grade crocidolite
      asbestos was used to generate a fibrous dust cloud whose size distribution was
      characterised by scanning and transmission electron microscopy and found to give
      a close approximation to the fibre size distributions monitored in 1938. Samples
      taken over the same sampling time, but at lower concentrations than originally
      sampled, showed that the thermal precipitator-oil immersion microscopy (TP-OI)
      method used at x 2000 magnification, gave higher > 5 microns long fibre counts by
      a factor of between 3 and 4, than the current MF-PCM method. The differences in
      performance could be explained by the superior resolving power of the TP-OI
      method for fine crocidolite fibres. Exposures of airborne asbestos fibres in the
      spinning area were found to be equivalent to about 20 f ml-1 for personal samples
      and 10 f ml-1 for area samples, but due to the high levels of ventilation on the
      day the samples were collected, the average levels throughout the year may have
      been somewhat higher.

PMID- 9566114
TI  - An investigation into the composition of products evolved during heating of hot
      melt adhesives.
AB  - The major chemical components generated by a selection of fourteen hot melt
      adhesives during heating have been identified. This information is required so
      that the possible health consequences of occupational exposure can be assessed
      and advice on controls developed. Details are also given of the test apparatus
      and standard testing procedure devised for this investigation. Analysis of the
      evolved material indicates the presence of a wide range of chemical compounds,
      including resin acids, volatile terpenes, aliphatic aldehydes, aliphatic and
      aromatic hydrocarbons and isocyanates. Some components, including resin acids and
      formaldehyde, are common to several types of adhesive, whereas others, such as
      acrolein and isocyanates, are specific to just one. There is no component which
      is characteristic of fume from all fourteen adhesives. Concentrations of
      individual chemical components show significant variation, both between different
      types of adhesive, and between samples of the same adhesive heated to different
      temperatures or for different periods of time. For individual adhesives,
      concentrations of evolved material tend to increase as the temperature of the
      glue is raised, with the highest levels being observed in samples taken directly
      after commencement of heating.

PMID- 9566113
TI  - Mechanisms of occupational asthma induced by isocyanates.
AB  - Isocyanates are some of the most important low molecular weight chemicals
      associated with occupational asthma. These compounds are often volatile and they
      are highly reactive on mucous membranes, especially the conjunctivae and
      respiratory tract. Despite numerous data derived from experimental and clinical
      investigations, there is no agreement concerning the real mechanisms involved in
      isocyanate-induced occupational asthma. In fact, the cause of occupational asthma
      is multifactorial. The aim of this paper is to review the involved physiological
      causes of isocyanate-induced asthma; the main mechanisms are immunological,
      pharmacological and/or irritative.

PMID- 9566115
TI  - The development of an improved method for the determination of coal tar pitch
      volatiles (CTPV) in air.
AB  - Test samples were collected at a range of sites using the MDHS 68 sampler, a 7
      hole sampler, and a cyclone respirable-dust sampler. Glass fibre, Zefluor,
      Fluoropore and silver (0.8 and 5 microns) filters were compared for weighing
      error, handling characteristics, and amount collected. The effects of a carbon
      back-up, of extraction solvent, and of analytical method were studied. The
      current HSE method for the sampling and analysis of coal tar pitch volatiles,
      MDHS 68 has been reviewed. It is recommended that the MDHS 68 sampler be replaced
      by a 7-hole head containing a silver or PTFE filter (approximately 1 micron pore
      size), with a graphitized carbon back-up if efficient collection of 2 to 4-ring
      PAHs is required. Cyclohexane is recommended as the extraction solvent. Methods
      of analysis which quantify the fume as a whole (MDHS 68, u.v., ELSD) were shown
      to give a response which varied according to the type of CTPV generating process.
      Therefore analysis of specific PAHs of occupational interest, by GC-MS or HPLC is
      recommended.

PMID- 9566116
TI  - Health effects of diesel emissions.

PMID- 9566117
TI  - Growth factor receptors: structure, mechanism, and drug discovery.
AB  - The focus of this review is the relationship between the three-dimensional
      structure of ligands of the various members of the growth factor receptor
      tyrosine kinase superfamily and their interaction with the cognate receptor.
      Particular attention is given to the transforming growth factor-alpha, epidermal
      growth factor (EGF); nerve growth factor, neurotrophin; and insulin-like growth
      factor-1 (IGF-1), insulin systems since these have been extensively studied in
      recent years. The three receptor types, which bind these ligands, are the
      epidermal growth factor receptor family (erb B receptors), the neurotrophin or
      Trk receptor family, and IGF-1/insulin receptors, respectively, and represent
      three distinct members of the tyrosine kinase superfamily. For each of these,
      formation of the ligand-receptor complex initiates the signal transduction
      cascade through autophosphorylation by the intracellular tyrosine kinase domain.
      The extracellular portion of the receptor that contains the ligand binding domain
      in these systems varies significantly in organization in each case. For the EGF
      receptor system, ligand binding induces homo- and heterodimerization of the
      receptor leading to activation of the intracellular kinase. For the Trk receptor
      system, homodimerization of receptors has been shown to occur, although a second
      receptor, p75, is also required for high affinity binding of neurotrophins and
      for enhanced sensitivity of tyrosine kinase activation at low ligand
      concentrations. The IGF-1 and insulin receptors exist as covalent cross-linked
      dimers where each monomer is composed of two subunits. The aim of this review is
      also to discuss the mechanism of ligand-receptor interaction for each of these
      cases; however, since no structural information is yet available for the ligand
      receptor complex, the discussion will largely be centered on the molecular
      requirements of ligand binding. As these receptors are activated through the
      ligand binding site on the extracellular domain, this represents a possible
      target for pharmacological intervention by inhibition or stimulation of this
      portion of the receptor. Thus from a drug design perspective, the focus of this
      review is to discuss progress in the development of agonists or antagonists of
      the ligand for these receptors.

PMID- 9566118
TI  - Immunoglobulin superfamily proteins: structure, mechanisms, and drug discovery.
AB  - We review the recent progress made in our laboratories in structure-based drug
      design targeting proteins of the immunoglobulin superfamily (IgSF). We will focus
      on the CD4 protein, which is involved in T cell function, as a specific example
      of how the general concept and methodologies can be applied. Recent studies of
      CD4 structure and function have revealed new insight into possible mechanisms for
      CD4 self-association and its role in binding to major histocompatibility complex
      (MHC) class II molecules and initiation of T cell activation. This has led to the
      formulation of a hypothetical model of co-oligomerization of CD4, MHC class II,
      and T cell receptor (TCR). Such a basic understanding of CD4 structure and
      mechanisms has aided the development of a new generation of potential
      immunotherapeutics targeting specific CD4 surface functional sites. The design
      and discovery of small molecular inhibitors of CD4 and other IgSF proteins, in
      peptide, peptidomimetic, and nonpeptidic organic forms have opened new avenues
      for chemical research in which peptide, organic, and more recently combinatorial
      chemistry techniques can be used to further develop these promising lead analogs
      into a new generation of effective pharmaceuticals.

PMID- 9566119
TI  - SH3 domains and drug design: ligands, structure, and biological function.
AB  - The ligand binding preferences, structural features, and biological function of
      SH3 (Src homology 3) domains are discussed. SH3 domains bind "core" Pro-rich
      peptide ligands (7-9 amino acids in length) in a polyproline II helical
      conformation in a highly conserved aromatic rich patch on the protein surface
      (approximately 390 A2). The ligands can interact with the protein in one of two
      orientations, depending on the position (N- vs C-terminal) of ligand residues
      binding to the SH3 selectivity pocket. Core SH3 ligands are characterized by
      relatively weak interactions (KD = 5-100 microM) that show little binding
      selectivity within SH3 families. Higher affinity, more selective contiguous
      ligands require additional flanking residues that bind to less conserved portions
      of the SH3 surface, with corresponding increase in ligand size and complexity. In
      contrast to peptide ligands, protein ligands of SH3 domains can exploit multiple
      discontiguous interactions to enhance affinity and selectivity. A protein-SH3
      interaction that utilizes unique interactions may permit the design of small high
      affinity SH3 ligands. At present, the extended nature of the binding site and
      homologous nature of the core binding region among SH3 domains present key
      challenges for structure-based drug design.

PMID- 9566120
TI  - Factors associated with the conditional release of persons acquitted by reason of
      insanity: a decision tree approach.
AB  - Most NGRI (not guilty by reason of insanity) acquitties are hospitalized for some
      period of time following acquittal, which raises the question of when an
      individual can be safely released into the community. The conditional release
      (CR) of persons acquitted by reason of insanity, therefore, provokes the question
      of public safety. This study examines the CR systems in four states--Connecticut,
      Maryland, New York, and Ohio. A study sample of 529 persons acquitted as NGRI
      from 1985 to 1987 was followed up for at least five years to determine who is
      conditionally released. Following a description of the CR systems, findings
      suggestive of the role of dangerousness and diagnosis as predictors of CR are
      presented. Personal characteristics are also significant factors in predicting
      who will be released. The length of hospitalization for this population and other
      descriptive factors such as history of hospitalization, arrests, substance abuse,
      family violence, and living arrangements are also addressed.

PMID- 9566121
TI  - Face-to-face confrontation: effects of closed-circuit technology on children's
      eyewitness testimony and jurors' decisions.
AB  - The present study was designed to examine effects of closed-circuit technology on
      children's testimony and jurors' perceptions of child witnesses. For the study, a
      series of elaborately staged mock trials was held. First, 5- to 6-year-old and 8-
      to 9-year-old children individually participated in a play session with an
      unfamiliar male confederate. Approximately 2 weeks later, children individually
      testified about the event at downtown city courtroom. Mock juries composed of
      community recruits viewed the trials, with the child's testimony presented either
      live in open court or over closed-circuit television. Mock jurors made ratings
      concerning the child witness and the defendant, and deliberated to reach a
      verdict. Results indicated that overall, older children were more accurate
      witnesses than younger children. However, older, not younger children produced
      more inaccurate information in free recall. Compared to live testimony in open
      court, use of closed-circuit technology led to decreased suggestibility for
      younger children. Testifying in open court was also associated with children
      experiencing greater pretrial anxiety. Closed-circuit technology did not diminish
      fact finders' abilities to discriminate accurate from inaccurate child testimony,
      nor did it directly bias jurors against the defendant. However, closed-circuit
      testimony biased jurors against child witnesses. Moreover, jurors tended to base
      their impressions of witness credibility on perceived confidence and consistency.
      Implications for the use of closed-circuit technology when children testify are
      discussed.

PMID- 9566122
TI  - Using the Referral Decision Scale to screen mentally ill jail detainees: validity
      and implementation issues.
AB  - The prevalence of serious mental illnesses in jail populations is significantly
      greater than in the general population. Identifying individuals who warrant
      psychiatric evaluations is important and benefits correctional staff as well as
      detainees. One widely used screening instrument intended for this task is the
      Referral Decision Scale (RDS). This paper reviews the development and validation
      of the RDS. Using data from a multisite study which assessed postrelease outcomes
      for detainees with mental illness, various types of validity are addressed. The
      results confirm that the RDS has some inherent characteristics that seriously
      limit its practical application as a screening instrument for use by correctional
      staff.

PMID- 9566123
TI  - Inflammation and apoptosis.
AB  - Apoptosis is a highly regulated form of programmed cell death defined by distinct
      morphological and biochemical features; it plays an important role in
      embryogenesis and the maintenance of cellular and tissue homeostasis in
      multicellular organisms. Its perturbation has been implicated in a wide range of
      patho-physiological stages, including autoimmune, bacterial, and viral disease,
      and degenerative disorders. The critical role of apoptosis in eliminating harmful
      or injured cells from tissues suggests its participation in inflammatory
      processes and in the resolution of inflammatory reactions. In this article, we
      briefly review the molecular mechanism of apoptosis and the role of apoptosis in
      inflammation.

PMID- 9566124
TI  - Studies on the effects of the spillway on the occlusal table of complete dentures
      upon the bearing of masticatory force.
AB  - We studied the effect of spillways in the posterior artificial teeth of complete
      dentures in reducing masticatory pressure on the basal mucosa by making
      completely edentulous patients masticate food. Using two kinds of experimental
      dentures, one with spillways on the occlusal table and the other without, five
      subjects wearing complete dentures were instructed to masticate four different
      types of test food. The results showed that the mastication time and the number
      of masticatory strokes were not much affected by the existence of spillways.
      However, the masticatory force of artificial teeth with spillways was slightly
      smaller than that of artificial teeth without spillways.

PMID- 9566125
TI  - Internal structure of the temporomandibular joint and the circumferential bone:
      comparison between dentulous and edentulous specimens.
AB  - To clarify changes in the trabecular structure due to loss of the teeth, the
      author compared soft X-ray images and morphological measurement values of the
      mandibular condyle and articular eminence between dentulous and edentulous
      specimens. The center of the skull base containing the temporomandibular joint
      was removed along the Frankfort horizontal and median sagittal planes. A block in
      the center of the cranial base was rejected using the Frankfort horizontal plane
      and median sagittal plane as references. The specimens were embedded in polyester
      resin by the routine method. The hardened specimens were horizontally cut into
      500 microns sections and photographed using soft X-ray films. Soft X-ray of each
      section was taken for observation by naked eye and morphometry by computer.
      Observation of the compact bone in the articular eminence showed thinner compact
      bone on the posterior slope of the articular eminence, which is a functional
      plane, than on the anterior slope of the articular eminence. There was a
      trabecular bone group on the lateral area running from the compact bone on the
      posterior surface of the articular eminence into the zygomatic arch and a thick
      trabecular bone group in a network pattern on the medial area. In the central
      area of the mandibular condyle, spongy bone was surrounded by oval compact bone,
      and the internal trabecular bone ran anteromedially in nearly the same pattern as
      the arrangement of the lateral pterygoid muscle. At all sites, the density,
      width, extent, and index indicating the complexity of the trabecular bone had
      higher values in dentulous specimens than in edentulous specimens.

PMID- 9566126
TI  - Soldering strength of post-soldering of palladium-based metal-ceramic alloys.
AB  - To evaluate the post soldering of metal-ceramic alloys that have palladium as
      their main component, palladium-based metal-ceramic alloys with different
      compositions were used to assess soldering strength. Four palladium-based metal
      ceramic alloys were selected: Pd-Cu system, Pd-Ag system, Pd-Ni system, and Pd-Sb
      system, and gold-silver-palladium alloy was also used. As soldering materials, 12
      k gold solder and 16 k gold solder were used. After post-soldering by butt joint
      samples that had been heat treated (equivalent to the porcelain firing cycle),
      soldering strength was evaluated by measuring the flexural strength. The yield
      strength had a range of 300 to 800 MPa, and the ultimate strength was in the
      range of 350 to 1,000 MPa; the Pd-Ag type showed the highest value. There was no
      correlation between the yield strength of the metal-ceramic alloys and that of
      the soldering samples. When the soldering strength of 12 k gold solder and 16 k
      solder were compared, the samples soldered with 12 k gold solder showed higher
      values in all cases. Samples in which heating was prolonged for 10 seconds had a
      high strength, within 100 to 500 MPa in yield strength and 100 to 800 MPa in
      ultimate strength.

PMID- 9566127
TI  - Corrosion resistance of the soldering joint of post-soldering of palladium-based
      metal-ceramic alloys.
AB  - To evaluate the corrosion resistance of post soldering of metal-ceramic alloys,
      four commercially available palladium-system metal-ceramic alloys (Pd-Cu, Pd-Ni,
      Pd-Ag, and Pd-Sb systems) and two types of solder (12 k gold solder and 16 k gold
      solder) with different compositions and melting points were used. The corrosion
      resistance of the soldered joint was evaluated by anodic polarization. The
      electrochemical characteristics of soldered surface were measured using
      electrochemical equipment. Declines in corrosion resistance were not detectable
      with Pd-Cu, Pd-Ag and Pd-Sb types, but break down at low potential occurred with
      Pd-Ni type.

PMID- 9566128
TI  - Light and electron microscopic study of autologous implants of dental roots in
      the subcutaneous tissue of rats.
AB  - Maxillary first molars of rats were extracted. The roots were separated and
      subsequently implanted in the dorsal subcutaneous tissue of the same animal. In
      Experiment 1, the roots were implanted immediately after removal; in Experiment
      2, the roots were subjected to freeze-thawing (devitalized) before implantation.
      After 4, 8, and 15 weeks of implantation, the roots were removed and processed
      for light and transmission electron microscopy. Roots of Experiment 1 showed an
      amorphous clear material filling depressions on the irregular surface of the
      cementum. This material consisted predominantly of collagen fibrils. Cells
      adjacent to the amorphous clear material exhibited numerous cytoplasmic processes
      surrounded by collagen fibrils. Globular structures with an electron-opacity
      similar to that of neighbouring cementum were observed within the bundles of
      collagen fibrils. Multinucleated cells with features of osteo/odontoclasts were
      often closely apposed to deep depressions of the cementum. In Experiment 2, only
      large multinucleated giant cells appeared around the surfaces of the roots. It
      seems therefore that, in Experiment 1, precementum formation and
      osteo/odontoclast mediated destruction occurred. It is likely that these
      activities may have originated from periodontal ligament cells carried to the
      implantation site. This conclusion is supported by the observation that such
      activities were absent in Experiment 2. Devitalized roots were unable to form
      precementum and were surrounded by foreign body giant cells.

PMID- 9566129
TI  - Self-reported oral hygiene habits, health knowledge, and sources of oral health
      information in a group of Japanese junior high school students.
AB  - The purpose of the present study was to analyze self-reported oral hygiene
      habits, sources of oral health information, and oral health knowledge in a group
      of Japanese junior high school students and to determine whether there is a need
      for improvement in the school's present oral health instruction. A sample of 110
      students aged 12-14 in Chiba City were surveyed by means of a questionnaire
      composed of 24 multiple choice questions. The questions focused on: (1)
      experience of school-based oral health education, (2) sources of oral health
      information, (3) knowledge about dental caries, periodontal disease, and the
      preventive action of fluoride, (4) oral hygiene habits, and (5) dietary behavior.
      Results showed that more than two-thirds of the students had participated in some
      kind of school-based oral health education program. Most students (76%) claimed
      that toothbrushing was the main event attended and 63% claimed that toothbrushing
      was the main subject they had been taught. The school nurse was identified by 48%
      of the students as their main source of oral health information in school-based
      oral health education. When asked to identify their main source of oral health
      information, most of the students identified "school". Half of the students (48%)
      identified dental plaque as the main cause of dental caries but only 31%, as the
      main cause of periodontal disease. Few students (11%) were able to identify the
      preventive action of fluoride; 58% answered "I don't know"). These results
      suggest that a meaningful target for the oral health education of children should
      be the improvement of the school's oral health instruction.

PMID- 9566131
TI  - A study on the grinding accuracy of a copy milling machine for dental use.
AB  - In order to assess the relationship between the profiling pressure of a copy
      milling machine for dental use and the accuracy of the dimensions of the objects
      produced, a Celay System was used to profile a metal-cylinder model, and its
      dimensions were compared with the workpieces. The results showed that, when a
      cylindrical model with a diameter of 6 mm was subjected to freehand profiling,
      the mean processing error of the object produced was -0.026 mm, and the profiling
      pressure was 4.6 gf to 131.7 gf (mean: 76.6 gf). However, the fluctuations in
      profiling pressure decreased by 1/5 during profiling operations when accessories
      that fixed the profiling pressure and the profiling loci were used. Moreover,
      while the processing error when the model was profiled at a profiling pressure of
      76 gf or less was a mere 0.005 mm, at 110 gf it rose to 0.022 mm. Based on the
      above, the processing error that occurred as a result of profiling pressure
      appeared to affect processing accuracy. On the basis of these findings, profiling
      as light weight must be performed with as possible in order to obtain accurate
      products using the copy milling machine for dental use, and the results suggested
      the necessity of attaching control devices to the copy milling machine to make
      accurate restorations.

PMID- 9566130
TI  - Protein synthesis dependent and independent apoptosis of murine splenic T cells.
AB  - To elucidate the mechanism of apoptosis in matured T cells, we examined the
      effect of phorbol esters capable of activating protein kinase C, cAMP agonists,
      calcium ionophores, and dexamethasone on apoptosis in mouse splenic T cells. All
      of these agents induced apoptosis in thymocytes. Neither phorbol esters nor
      calcium ionophores induced apoptosis in the splenic T cells. Dibutyrylcyclic AMP
      induced apoptosis in splenic T cells but to a lesser extent than that in
      thymocytes. The results suggest that matured T cells are more resistant to
      various apoptogenic stimuli than thymocytes. Dexamethasone induced apoptotic cell
      death in splenic T cells as well as in thymocytes. Cycloheximide, an inhibitor of
      protein synthesis which completely inhibited thymocyte apoptosis, induced slight
      apoptosis in splenic T cells, but it inhibited the dexamethasone-induced
      apoptosis to a level at which cycloheximide induced apoptosis, indicating that at
      least two pathways of apoptosis exist in peripheral T cells; one protein
      synthesis dependent and the other independent. Taken together, the results
      suggest that the apoptosis of peripheral T cells is regulated by a mechanism
      different from that of thymocytes.

PMID- 9566132
TI  - Measurements of cytosolic free Ca2+ concentrations in odontoblasts.
AB  - To investigate the responsiveness of odontoblasts to electrical and mechanical
      stimuli, the concentrations of cytosolic free Ca2+ ([Ca2+]i) were measured using
      fura-2 microfluorometry in slice preparations of rat dental pulp. [Ca2+]i under
      resting conditions (basal [Ca2+]i) were 258.0 +/- 37.7 nM (mean +/- S.E., n =
      113). The basal [Ca2+]i of the odontoblasts with remarkably active responses to
      stimuli were 221.0 +/- 81.1 nM (mean +/- S.E., range: 16-685 nM). Depolarization
      by high extracellular K+ concentration ([K+]o) caused a rapid increase in
      [Ca2+]i. The depolarization-induced increase in [Ca2+]i was enhanced by caffeine.
      The intense depolarization elicited [Ca2+]i oscillation in odontoblasts, which
      was enhanced by caffeine and suppressed by dantrolene. Hypotonic stimulation also
      induced an increase in [Ca2+]i of odontoblasts. The results indicate that the
      odontoblast possesses voltage-dependent Ca2+ channels, caffeine-sensitive Ca2+
      stores and mechanosensitive cation channels.

PMID- 9566133
TI  - Immunolocalization of proliferating cell nuclear antigen in the peri-implant
      epithelium.
AB  - The aim of the present study was to investigate the proliferating activity of
      peri-implant epithelium immunohistochemically using proliferating cell nuclear
      antigen (PCNA). Eight ITI (Internationale Team fur Implantologie) implants were
      placed into simulated sockets in the mandibles of two beagle dogs two months
      following tooth extraction. As a control, junctional epithelium of the molar
      teeth in the same animals were used. The nature of staining and the distribution
      of PCNA immunoreactivity were determined by scoring a minimum of 100 cells on two
      sections from each of the implants. In the junctional epithelium, the
      immunoreactivity to PCNA was detected mainly in the basal cells, in some of the
      prickle cells, and in a few cells attached to the enamel. In peri-implant
      epithelium, only some of the basal cells were positive for PCNA. The PCNA score
      of the peri-implant epithelium was significantly lower than that of junctional
      epithelium. These results suggest that the peri-implant epithelium maintains a
      lower capacity to act as a proliferative defence mechanism than does the
      junctional epithelium.

PMID- 9566134
TI  - Immuno-histochemical demonstration of alpha-tubulin distribution in rat incisor
      ameloblasts after vinblastine administration.
AB  - This study used the immunoperoxidase method to demonstrate post-vinblastine
      administration distribution of alpha-tubulin, a structural component of the
      microtubule, in rat incisor secretory-stage and maturation-stage ameloblasts.
      Immunostaining for alpha-tubulin in secretory-stage ameloblasts and maturation
      stage ameloblasts decreased from 1 hr to 6 hrs after vinblastine administration.
      At 12 to 24 hrs after administration, it appeared to begin recovering from the
      distal region of the cytoplasm toward the proximal side of the cytoplasm and, by
      48 hrs after administration, had almost reached control levels. In both stages,
      ameloblast cell shapes and organelle polarities changed concurrently after the
      decrease in alpha-tubulin staining.

PMID- 9566135
TI  - Occlusal migration of the maxillary first primary molars subsequent to the loss
      of antagonists.
AB  - The purpose of this study was to observe the vertical changes in unopposed
      maxillary first primary molars longitudinally. The subjects of this study were 17
      children whose lower first primary molars had to be extracted. Space closure were
      prevented by crown-loop space maintainers for all these children. Plaster casts
      were made every 4 months for 16 to 24 months after the extraction. These series
      of casts were standardized, and vertical changes of the maxillary first primary
      molars against the occlusal plane were measured using a micro-reader. The mean
      changes indicated that maxillary first primary molars without intercuspidation
      tend to drift toward the extraction space. On the control side with antagonists,
      the maxillary first molars seemed to move reversed to apical throughout the
      observation period. Accordingly, the results of this study showed new trends
      after the premature loss of primary molars. The vertical changes toward
      extraction space varied from -0.40 mm to 1.43 mm at the 16 months after
      extraction. Mean changes were small, but there were some individual differences
      in reaction, giving negative values. However, we should always be concerned about
      loss of arch length and also occlusal drift of unopposed teeth, because the
      vertical changes were greater than 1 mm at 16 months after extraction in some
      cases.

PMID- 9566136
TI  - Anatomical study of the pectoral branch of thoracoacromial artery.
AB  - Reconstructive surgery uses various musculocutaneous flaps following resection of
      head and neck malignant tumor. Numerous anatomical studies have reported that the
      thoracoacromial artery arises from the axillary artery, but those findings have
      not been completely confirmed. The aim of this study was to investigate the path
      from the origin of the thoracoacromial artery until its pectoral branches enter
      the pectoralis major muscle. The following results were obtained. 1. There were
      no cases in which the thoracoacromial artery arose from the third part of the
      axillary artery. 2. There were differences between the left and right sides in
      the vertical and horizontal origins of the thoracoacromial artery in relation to
      the clavicle and median line. 3. Pectoral branches showed a single origin from
      the thoracoacromial artery most frequently. 4. Pectoral branches descend in
      parallel to the median line most frequently on the right side and descended
      medially to the median line most frequently on the left side. 5. The largest
      number of branches approached the venter vertically at the height of the third
      rib. There findings suggest that, during operations involving a musculocutaneous
      flap, the surgeon must pay attention to the differences in vascular morphology of
      the right and left sides.

PMID- 9566137
TI  - Anatomical study of arrangement and attachment of the medial pterygoid muscle in
      Japanese men.
AB  - We precisely examined the origin, attachment, manner and insertion of the medial
      pterygoid muscle to clarify the relationship between muscle morphology and
      mastication movement. The muscular bundle attachment of the medial pterygoid
      muscle at the origin could be divided into three types; 1) the muscle was
      attached to the inner surface of the medial pterygoid plate with a strong tendon,
      2) to the posterior maxilla wall with a strong tendon, and 3) directly to the
      periosteum of the inner surface of the lateral plate without a tendon. Provided
      that the muscular bundles had a firmly tendinous attachment under strong and
      significant force during their functioning, significant force would be applied to
      the medial pterygoid muscle in two directions. Observations of the intersection
      with the medial pterygoid muscle in the posterior wall of the maxillary bone at
      the origin revealed intersecting fibers or tendon fusion in all 55 specimens.
      Since there are different muscular bundle groups within the medial pterygoid
      muscle, we expect to elucidate more of masticatory function by observing other
      masticatory muscles as well as the medial pterygoid muscle.

PMID- 9566138
TI  - A case of desmoplastic ameloblastoma of the maxilla.
AB  - A case of desmoplastic ameloblastoma of the maxilla is presented. The tumor
      showed characteristic radiographical and histological features. Radiographically,
      the tumor showed a mixed radiolucent-radiopaque lesion occupying the left
      maxillary sinus with undefined borders in the alveolar process.
      Histopathologically, the tumor was characterized by abundant, densely collagenous
      stroma with small nests and strands of odontogenic epithelium and bone tissues.
      Findings during operation suggested that the tumor arising in the alveolar
      process had grown upwards and almost displaced the left maxillary sinus. Complete
      resection is recommended for this variant because of the possibility of tumor
      infiltration into the surrounding bone marrow spaces.

PMID- 9566139
TI  - Dental diseases and gastroenterology.
AB  - Recently, the relationship between digestive diseases and oral diseases has been
      a focus of interest. Physicians and dentists should not simply diagnose diseases
      without understanding the possible relationships between the mouth and digestive
      system, such as double cancers in oral cavity and esophagus or stomach.
      Physicians should learn to examine the mouth systematically. On the other hand,
      dentists should not only treat dental caries, periodontitis, and denture
      problems, but should also study medical knowledge in order to develop dental
      treatment for total oral health care. In other words, dentists should become oral
      physicians or stomatologists. In this paper, we describe how digestive diseases
      relate to oral diseases and the important systemic findings you can deduce from
      oral findings. We hope that the knowledge presented here will be helpful for
      dentists and physicians in their daily practice.

PMID- 9566140
TI  - On the linearization of eruption series of the permanent teeth.
AB  - In order to confirm the linearization of permanent eruption, Masuyama's
      linearization method was applied to the data of Kitamura's study. At first, we
      considered the eruption age t alpha i of permanent teeth T alpha, where alpha
      corresponds a tooth of every description, and examined the linear regression of Y
      alpha i = log10 t alpha i on m(y) alpha (the mean of Y alpha i with respect to
      i), but the result was not good. For the correlation coefficient r between two
      variables in linear regression, the percentage of subjects with r > or = 0.970
      was only 10.3% in males and 28.8% in females in Kitamura's study. Next we took
      notice of the eruption age u beta i of each tooth, which is the beta-th in order
      of eruption. The fitness of the linear regression of Z beta i = log10 u beta i on
      mz beta (the mean of Z beta i) was very good. The percentage of subjects with r >
      or = 0.970 increased to 80.0% in males and 86.0% in females. Then we used m(y)
      (beta) (rearranged m(y) alpha in order of increasing size) instead of mz beta as
      an independent variable in the linear regression. The degree of the linearization
      was slightly inferior to that using mz beta. In every linearization, a quasi
      fixed point with coordinates (C, C) existed on the linearized dentition plot,
      where the value of C was almost equal in each way, i.e., C = 10.23 (years) for
      males and C = 8.91 (years) for females in Kitamura's data. This linearized
      dentition plot will be useful in detecting certain growth disturbances. The
      existence of a quasi-fixed point may be useful in forecasting the age of the
      eruption of subsequent teeth, once the first eruption is observed.

PMID- 9566142
TI  - Soft laser irradiation effects on pain reduction in orthodontic treatment.
AB  - The effects of soft laser (low reactive level laser) on reduction of pain while
      undergoing orthodontic treatment was examined in this study. These patients were
      randomly separated into 3 groups: non-treated control group (CG), blind
      irradiation group (BG), and laser irradiated group (LG). The effect of laser
      irradiation on reduction in pain was analyzed by a questionnaire given to
      patients who had been wired with an edgewise appliance of a multi-bracket system
      for orthodontic therapy. Just after application of the initial wire, LG patients
      were irradiated with the soft laser from the labial and lingual sites for a total
      of one minute. Reduction in pain was found in some patients who had been
      irradiated. In particularly, delay in the pain appearance was noted as compared
      to the other two control groups.

PMID- 9566141
TI  - A study of the growth changes in the maxillofacial skeleton of females with
      reversed occlusion: investigation by means of lateral x-ray cephalogram.
AB  - 321 females with reversed occlusion from the ages of 6 to 20 were classified into
      15 groups according to chronological age, and the changes of maxillofacial
      skeleton accompanying growth were investigated. Lateral cephalometric
      roentgenogram before treatment of the subjects were used for analyses and
      measurements of maxillofacial skeleton and overjet. The cephalometric analysis
      was standardized on the S-N plane, and 5 angular items and 6 linear distances
      were examined. The results of the investigation are summarized as follows: (1)
      angle ANB, the relationship between the upper and lower jaws, deteriorated to a
      minus degree from the age of 9 and became -3.3 degrees at the age of 14. Skeletal
      convexity became negative from the same age and was -7.3 degrees at the age of
      14. Thus, the abnormal skeletal features progressed in this condition. (2) The Ar
      Gn distance measurement gradually increased from the age of 6 to 18. The increase
      was 16.2 mm from 7 to 12, an increase of 3.2 mm yearly. (3) A high correlation (r
      = 0.99) was observed between angle ANB and Convexity. As well, a high coefficient
      of correlation (r = 0.87) was observed between skeletal convexity and soft tissue
      convexity. The change in soft tissue convexity may occur 3-4 years later than
      that of skeletal convexity. (4) The growth curve of Ar-Gn became a logistic curve
      with the point of deflection at the age of 10.87. The growth curves of S-Gn and N
      Me became logistic curves in the same way.

PMID- 9566143
TI  - Bactericidal effects of mouth rinses on oral bacteria.
AB  - The bactericidal efficacy of two types of Listerine; Listerine and Cool Mint
      Listerine, and povidone iodine on oral microorganisms, methicillin-resistant
      Staphylococcus aureus (MRSA), Streptococcus pyogenes, Helicobacter pylori and
      Candida albicans were examined. Most of the oral bacteria were killed completely
      by a 10-sec exposure to Listerine or Cool Mint Listerine. H. pylori, MRSA and C.
      albicans were also reduced by a 30-sec exposure to the Listerine mouth rinse.
      Bacteria in dental plaque were decreased by exposure to Listerine, Cool Mint
      Listerine, and povidone iodine for 30 seconds. Mouthwashing with Listerine for 30
      seconds resulted in a decrease to approximately 1/100 of the viable bacterial
      counts in saliva. These bactericidal effects against bacteria in saliva and
      dental plaque indicated that Listerine and Cool Mint Listerine antiseptic are
      useful in oral cavity as antiseptic mouth rinses.

PMID- 9566144
TI  - A morphological study for isolation of a single rat trigeminal motoneuron.
AB  - We conducted a morphological study for isolation of a single neuron to
      investigate the electrophysiological properties of trigeminal motoneurons in a
      further study using the patch clamp technique. Transverse slices of rat brain
      stem containing the trigeminal motor nucleus (200-300 microns thick) were
      prepared and stained by the methylene blue staining method. The trigeminal motor
      nuclei, approximately 1,000 microns in diameter, were identified as densely
      stained regions in the slices. The somata of motoneurons were classified into two
      types by shape; ellipsoidal and spherical. The ellipsoidal somata were 50.3 +/-
      12.3 microns (mean +/- S.D., n = 290) in long axis and 21.8 +/- 5.3 microns (n =
      290) in short axis. The spherical somata were 35.0 +/- 6.9 microns (n = 290) in
      long axis and 29.3 +/- 5.7 microns (n = 290) in short axis. The neurons were all
      multipolar with 2-8 dendrites emanating from the soma.

PMID- 9566145
TI  - An HRP study of the distribution of primary afferent neurons innervating the
      buccal stretch receptor in rats.
AB  - Retrograde transport of horseradish peroxidase conjugated with wheat germ
      agglutinin (WGA-HRP) was used to observe the ganglionic origin of primary
      afferent neurons innervating the buccal stretch receptor (BSR) in the rat. WGA
      HRP was applied to the proximal stump of the severed nerve branch innervating the
      BSR. HRP-labeled cell bodies were observed only in posterolateral portion of the
      ipsilateral trigeminal ganglion. The diameter of these cell bodies was 25.5-52.5
      microns, of which 54.9% was in the range of 31-40 microns and 36.3% larger than
      41 microns. Taken together with its ontogenetic origin, the BSR is suggested to
      have differentiated from the mechanoreceptors in the oral mucosa or the fascia of
      masticatory muscles.

PMID- 9566147
TI  - Essential research projects of oral health science in Tokyo Dental College for
      the 21st century.
AB  - In this era of an aging society, no longer will it be sufficient for us to sit in
      small research units and concentrate on individual experiments. Tokyo Dental
      College must expand its abilities and develop new attitudes to meet society's
      evolving needs. The Search Eye 21 will provide us with new opportunities to
      identify such research goals and to unite coordinated efforts for the advancement
      of oral health science.

PMID- 9566146
TI  - Repair of a cheek defect with the tissue expander method: a case report.
AB  - A 28-year-old female had a severe depressed deformity of the left cheek due to
      false local injection of ZnCl2 into her buccal mucosa instead of an anesthetic.
      After several attempts at plastic surgery in another hospital with unsatisfactory
      results, she was treated surgically in our clinic using cheek skin expanded by a
      tissue expander. The outcome was satisfactory.

PMID- 9566148
TI  - Vascular consideration in raising the pectoralis major flap.
AB  - Several types of musculocutaneous flaps, including that the pectoralis major,
      have been used for reconstruction following resection of malignant tumors in the
      head and neck region. Although several clinical studies have investigated the
      vascularity of such musculocutaneous flaps, the findings have been inconsistent.
      The present study examined the distribution of arteries in the pectoralis major
      muscle and surrounding subcutaneous tissue by macroscopic dissection and
      angiography. Based on the results of this examination, muscle layer and
      surrounding subcutaneous tissue appear to be supplied by different arteries and
      show different distribution patterns. However, evidence of penetrating branches
      from the muscle layer to the subcutaneous tissue layer suggests the existence of
      blood flow from the muscle layer to the subcutaneous tissue layer. Such arterial
      branches should be considered when raising the pectoralis major flap in order to
      prevent necrosis and improve the viability of the flap.

PMID- 9566149
TI  - Responses of peri-implant tissues to undisturbed plaque formation in dogs:
      clinical, radiographic, and microbiological findings.
AB  - The present investigation evaluated the clinical and microbiological effects of
      long-term undisturbed plaque formation on peri-implant tissues. Four mongrel dogs
      were used in the study. The mandibular 3rd and 4th premolars were extracted.
      Three months later, four Branemark implants (BR, n = 8) or Integral implants (IN,
      n = 8) were placed in the edentulous area of each dog. After another 3 months, an
      abutment connection was performed. Plaque control regiment was maintained for 30
      days until the superstructure was placed (Day 0: baseline). Then the plaque
      control program was terminated to allow gross plaque accumulation. Clinical,
      radiographical and microbiological data were recorded at the baseline, and at 90
      and 180 days after the termination of the plaque control. Values for the clinical
      indices such as probing depth, plaque index and bleeding on probing increased at
      day 90 on both the implant and tooth sites, and remained unchanged at day 180.
      Significantly more implant sites showed bleeding on probing than did tooth sites.
      Neither implants nor tooth sites showed clinically significant changes in
      mobility. No distinct bone resorption was observed over time by radiography. In
      microscopic morphological observations, cocci dominated at the baseline, and
      decreased by day 180, while the proportion of motile bacteria increased. In a
      culture study, black-pigmented anaerobic rods, which consisted predominantly of
      Porphyromonas gingivalis-like bacteria, were consistently found from the baseline
      to day 180. No Actinobacillus actinomycetemcomitans-like organisms were isolated.
      These results indicate that, although the long-term plaque accumulation did not
      cause marked periodontal destruction, the peri-implant tissue may be more
      susceptible to plaque accumulation than the periodontal tissue, and that teeth
      may serve as a reservoir for the bacterial colonization of the implant sulcus.

PMID- 9566150
TI  - Radiation dosage reduction in general dental practice using digital intraoral
      radiographic systems.
AB  - This report describes the radiation dosage reduction possible in the general
      dental practice with two CCD (charge-coupled device)-based intraoral radiographic
      systems: the RVG-S (Trophy Radiologie, Vincennes, France) and the Sens-A-Ray
      (Regam Medical Systems, Sundsvall, Sweden). Radiation dosages (air-kerma; Gy)
      necessary for obtaining clinically acceptable images were measured at the cone
      tip using an ionization chamber type 660-1 (Nuclear Associates, Victoreen, Inc.,
      Carle Place, New York, USA). When the RVG-S was used with an Oramatic 70 (Trophy
      Radiologie) X-ray generator, dosages at the cone tip ranged from 322 to 612
      microGy. These corresponded to 40-60% of the dosages necessary when using
      Ektaspeed dental X-ray film (Eastman Kodak, Rochester, New York, USA) with a
      Heliodent 70 (Siemens, Erlangen, Germany) X-ray generator. At 60 kVp, the Sens-A
      Ray reduced the dosage in the order of 30% compared with Ektaspeed dental X-ray
      film. Reduction in radiation dosage is one of the benefits of digital intraoral
      radiographic systems in general dental clinics. The RVG-S provides greater dose
      savings than does the Sens-A-Ray.

PMID- 9566151
TI  - Prevalence of congenital dental anomalies of the deciduous dentition in Japanese
      children.
AB  - We examined the prevalence of anomalies in deciduous dentition in 2,733 Japanese
      three-year-old children. The results showed that fused teeth occurs in 4.10%,
      congenital missing teeth in 2.38%, enamel hypoplasia in 1.50%, peg-shaped teeth
      in 0.55%, palatal cusps in upper deciduous incisors in 0.37%, supernumerary teeth
      in 0.07%, and color anomalies in 0.07%. Sixty-nine boys and 43 girls had fused
      teeth, percentages of 4.88 and 3.26, respectively. This difference was
      significant. All the fused teeth were located in the anterior region and were
      more frequent in the mandibular than in the maxillary arch. In the mandibular
      arch, 50 cases involved the lateral incisor and canine; the central incisor and
      lateral incisor were fused in 48 instances. There were 30 boys (2.12%) and 35
      girls (2.65%) with congenitally missing deciduous teeth. This difference was not
      significant. Unilateral missing teeth were more frequently observed than
      bilateral missing ones. The lower lateral deciduous incisor was the most
      frequently missing tooth. The prevalences of fused teeth and congenital missing
      teeth were significantly higher in this study than in studies of American and
      Scandinavian children. These two anomalies are tending to increase in frequency
      in Japan.

PMID- 9566152
TI  - A dynamic study of the effect on the maxillofacial complex of the face bow:
      analysis by a three-dimensional finite element method.
AB  - In order to investigate the effects of a face bow on the maxillofacial complex,
      we applied an analysis by a finite element method. To create a skull model, we
      measured an adult skull sample, and constructed a left lateral model without a
      mandible with 11 bones of 11 types, 30 sutures, and 3 synchondroses. The numbers
      of elements and nodes in the model were 1,207 and 1,539, respectively. The
      numbers of elements in the face bows used were 16 for the short type and 22 for
      the long one, respectively. Both of them were directly connected to the first
      molar tooth. To establish the constraining conditions, a symmetrical condition at
      the center of the model was chosen, and the basal part of the occipital bone was
      completely fixed. Each 1 kg loading was applied in three directions: 30 degrees
      post-superior, 0 degree posterior, and 30 degrees post-inferior. The results from
      this face bow loading experiment showed that the direction of displacement and
      the stress distribution were significantly different among the kinds of the face
      bows and the loading directions. For the short type face bow, simple compression
      appeared due to the post-superior loading and bending deformation due to the
      posterior and post-inferior ones. For the long type face bow, some bending
      deformations appeared, including anterior-elongation and posterior compression
      due to the post-superior loading. Post-inferior bending due to posterior loading
      and post-inferior bending and inferior displacement due to the post-inferior
      loading also appeared. Thus it is feasible to dynamically control the
      maxillofacial complex form by changing the type of the face bow and the direction
      of the loading traction.

PMID- 9566153
TI  - Condylar surface forms in edentulous patients: examination findings.
AB  - The incidence of abnormal condylar surface forms was assessed by zonograms on
      edentulous patients who visited this department with various chief complaints
      other than temporomandibular disorder. The relation between these abnormal
      condylar surface forms and the conditions involved in the manifestation of the
      abnormalities was studied. Abnormal condylar surface forms were observed in 71%
      of the subjects. Bilateral abnormalities were found in 66% of these subjects:
      These abnormalities were classified into four types: erosion, flattening,
      osteophyte, and concavity. Those with erosion showed the highest incidence at
      60.6%. The incidence of abnormal condylar surface forms was significantly higher
      in patients over 70 years old and/or in unstable denture wearers.

PMID- 9566154
TI  - A study on the evaluation of masticatory ability in osseointegrated implants
      applied to lower molar region.
AB  - Masticatory function was investigated in 7 subjects (5 women and 2 men) with
      unilateral OIB in their lower molar region. Masticatory movement and myoelectric
      discharge were analyzed. To examine occlusal contact, the closely occlusal
      contact area and occluding forces were investigated. The results from the OIB
      side were compared with the ones from the opposite side. In all subjects, there
      were no significant differences in the parameters of mandibular movement between
      chewing the test foods on the OIB side and chewing them on the opposite side. In
      6 out of 7 subjects, the closely occlusal area of the interocclusal space
      differed by less than 1.0 mm between the OIB side and the opposite side in the
      molar region, and the occluding forces between them were similar. In 6 out of 7
      subjects, the masticatory sensations were also similar between the two sides.
      There were no significant differences between the OIB side and the opposite side
      in the parameters of mandibular movement, the condition of occlusal contact and
      the sensation of mastication in patients who were treated with unilateral OIB in
      the lower molar region. The data seem to suggest that there is little difference
      between the masticatory ability of OIB and that of natural dentition.

PMID- 9566155
TI  - Combined orthodontic/TMJ treatment in general practice. Report of a court case.

PMID- 9566156
TI  - Criteria used to establish the ideal plane of occlusion. Part II.

PMID- 9566157
TI  - Clinical application of psychometric analysis for temporomandibular dysfunction.
AB  - The proper diagnostic modalities needed for detecting a temporomandibular
      dysfunction should include testing procedures from three distinct arenas of data.
      Those encompass anatomic diagnostic imaging, physiologic testing and psychometric
      analysis. This article addresses the clinical pretreatment uses and benefits, as
      well as the post treatment application of a specific psychometric analysis, the
      TMJ Scale. Additionally, medical-legal issues and case studies are provided.

PMID- 9566158
TI  - Twin Block appliance. Part II.
AB  - The main purpose of the Twin Block is to advance the mandible and to correct
      moderate to severe overjets. When the first molars are encouraged to erupt, the
      Twin Block also results in a partial correction of the overbite. The Rick-A-Nator
      or Rick-A-Nator 2 Appliances are utilized to hold the mandible in a forward
      position and also to help erupt the bicuspids to complete the orthopedic
      correction of the overbite. It is vital that the total treatment time for the
      active phase with the Twin Block and the support phase with the Rick-A-Nator be a
      minimum of 15 to 18 months to allow for permanent muscular, skeletal and dental
      changes to be accomplished.

PMID- 9566159
TI  - Alternatives to extraction orthodontics: a nitanium palatal expander.

PMID- 9566160
TI  - Snoring. What's all the noise about?

PMID- 9566161
TI  - ALF appliance design conforms to functional cranial anatomy.

PMID- 9566162
TI  - TMJ orthodontics.

PMID- 9566163
TI  - Criteria used to establish the ideal plane of occlusion. Part I.

PMID- 9566164
TI  - Non-surgical correction of Class III malocclusion.

PMID- 9566165
TI  - Indication of the Rossi orthopedic appliance: a case study.

PMID- 9566166
TI  - The 10 great laws of orthodontics. Part II. Laws VI-X.

PMID- 9566167
TI  - A modified, lingually supported cantilevered Herbst appliance.
AB  - This new, fixed-functional appliance/Herbst/Bioprogressive system is designed for
      patient comfort and mandatory compliance. It also combines the positive clinical
      effects of four fixed-functional systems. It allows rapid palatal expansion of
      the upper arch, alveolar uprighting of the lower arch, upper and lower incisor
      alignment, and sagittal correction of Class II malocclusions to occur
      simultaneously with one appliance fixed in both arches. It is indicated for use
      in growing patients with skeletal Class II malocclusions. The ideal timing for
      treatment is the late mixed dentition. Being able to remove the appliance after
      one year with the upper second bicuspids erupting slightly Class III so the
      clinician can immediately begin fixed finishing mechanics would be ideal. This
      new Herbst design will reduce the frequency of orthognathic surgery and upper
      bicuspid extraction to camouflage Class II malocclusions. At the same time, it
      gives total control to the clinician in treating some more difficult, non
      compliant patients. Fixed-functional appliances, which improve treatment
      efficiency and treatment results and provide for patient comfort, while at the
      same time give the treating clinician almost total control of the three planes of
      facial growth will open new doors for orthodontic treatment and research in the
      next century.

PMID- 9566169
TI  - The standardization of the temporal-mandibular joint.

PMID- 9566168
TI  - FJO in early interceptive orthodontics or "prophylactic orthodontics". Functional
      jaw orthopedics.

PMID- 9566170
TI  - New methods of construction and action of Herbst thermoformed splint appliances.

PMID- 9566171
TI  - Guidelines for the surgical management of breast cancer. Council of the Royal
      Australasian College of Surgeons.

PMID- 9566173
TI  - Approaching death: improving care at the end of life--a report of the Institute
      of Medicine.

PMID- 9566172
TI  - Foreign bodies in the pediatric patient.

PMID- 9566174
TI  - HSR: Health Services Research annual report to our readers and the field,
      September 1, 1996 through August 31, 1997.

PMID- 9566175
TI  - Do vouchers improve breast cancer screening rates? Results from a randomized
      trial.
AB  - OBJECTIVE: To determine the effect of a voucher for free mammography on
      compliance with recommended mammography screening guidelines. STUDY DESIGN:
      Vouchers for free mammography distributed to a random sample of women over the
      age of 50 in two rural southern Minnesota counties. The vouchers were good for
      one year. Baseline and follow-up data were collected and rates of compliance with
      current mammography guidelines were observed for the voucher group and a control
      group of women living in the same counties. METHODS: Logistic regression models
      were used to estimate the effect of the voucher on compliance with mammography
      guidelines and the impact of factors potentially influencing the effectiveness of
      the voucher. PRINCIPAL FINDINGS: The voucher improved mammography rates primarily
      through increasing screening among women who were out of compliance at baseline.
      CONCLUSIONS: Vouchers, even when distributed randomly within a population of
      rural Midwestern women, can significantly improve compliance rates. Vouchers are
      no less effective a means of increasing screening among vulnerable women than
      among other women.

PMID- 9566177
TI  - A comparison of capitated and fee-for-service Medicaid reimbursement methods on
      pregnancy outcomes.
AB  - OBJECTIVE: To determine if the payment method influenced the likelihood of
      selected obstetrical process measures and pregnancy outcome indicators among
      Medicaid women. DATA SOURCE/STUDY SETTING: Data from the live birth certificates
      computer file for 1993 from the State of California. The computer files contain
      information about the demographic characteristics of the mother, her medical
      conditions prior to delivery, medical problems during labor and delivery,
      delivery method, newborn and maternal outcomes, and expected principal source of
      payment for prenatal care and for hospital delivery. STUDY DESIGN: The study
      sample consisted of singleton live births to women in the California Medi-Cal
      program residing in one of two counties in which a mixed-model managed care plan
      was the method of reimbursement or in one of three counties in which fee-for
      service was the payment method. The study and control counties were matched in
      terms of geographic proximity and sociodemographics. PRINCIPAL FINDINGS: Among
      Medi-Cal women, the likelihood of low birth weight (LBW) was lower in the
      capitated payment group than in the fee-for-service payment group even when
      controlling for maternal and newborn characteristics and adequacy of prenatal
      care. There was no difference in either the adequacy of prenatal care, the
      cesarean birth rate, or the likelihood of adverse pregnancy outcomes other than
      LBW between the two payer groups. CONCLUSIONS: Results of this "natural
      experiment" suggest that enrollment of pregnant Medi-Cal beneficiaries in
      capitated healthcare services through a primary care case management system in a
      county-organized health system/health insuring organization can have a beneficial
      effect on low birth weight and provide care comparable to a fee-for-service
      system.

PMID- 9566176
TI  - Factors associated with women's adherence to mammography screening guidelines.
AB  - OBJECTIVE: To examine individual and environmental factors associated with
      adherence to mammography screening guidelines. DATA SOURCES: A unique data set
      that combines a national probability sample (1992 National Health Interview
      Survey); a national probability sample of mammography facility characteristics
      (1992 National Survey of Mammography Facilities); county-level data on 1990 HMO
      market share; and county-level data on the supply of primary care providers (1991
      Area Resource File). STUDY DESIGN: The design was cross-sectional. DATA
      EXTRACTION/ANALYSIS: Data sets were linked to create an individual-level sample
      of women ages 50-74 (weighted n = 2,026). We used multipart, sequential logistic
      regression models to examine the predictors of having ever had mammography,
      having had recent mammography, and adherence to guidelines. We categorized women
      as adherent if they reported a lifetime number of exams appropriate for their age
      (based on screening every two years) and they reported having had an exam in the
      past two years. PRINCIPAL FINDINGS: Only 27 percent of women had the age
      appropriate number of screening exams (range 16 percent-37 percent), while 59
      percent of women had been screened within two years. Women were significantly
      more likely to adhere to screening guidelines if they reported participating with
      their doctor in the decision to be screened; were younger; had smaller families,
      higher education and income, and a recent Pap smear; reported breast problems;
      and lived in an area with a higher percentage of mammography facilities with
      reminder systems, no shortage of primary care providers, higher HMO market share,
      and higher screening charges. CONCLUSIONS: A small percentage of women adhere to
      screening guidelines, suggesting that adherence needs to become a focus of
      clinical, programmatic, and policy efforts.

PMID- 9566178
TI  - Commentary: burden of proof in an era of outcomes research and managed care.

PMID- 9566179
TI  - How do HMOs achieve savings? The effectiveness of one organization's strategies.
AB  - OBJECTIVE: To examine how a group practice used organizational strategies rather
      than provider-level incentives to achieve savings for health maintenance
      organization (HMO) compared to fee-for-service (FFS) patients. DATA SOURCES/STUDY
      SETTING: A large group practice with a group model HMO also treating FFS
      patients. Data sources were all patient encounter records, demographic files, and
      clinic records covering 3.5 years (1986-1989). The clinic's procedures to record
      services and charges were identical for FFS and HMO patients. All FFS and HMO
      patients under age 65 who received any outpatient services during approximately
      100,000 episodes of the seven study illnesses were eligible. STUDY DESIGN: Using
      an explanatory case design, we first compared HMO and FFS rates of resource
      utilization, in standardized dollars, which measured the impact of organizational
      strategies to influence patient and provider behavior. We then examined the
      effect of HMO insurance and organizational measures to explain total outpatient
      use. Key variables were standardized charges for all outpatient services and the
      HMO's strategies. PRINCIPAL FINDINGS: Patient and provider behavior responded to
      organizational strategies designed to achieve savings for HMO patients; for
      instance, HMO patients used midlevel providers and generalists more often and ER
      and specialists less often. Overall HMO savings, adjusted for case mix, were
      explained by the specialty of the physicians the patients first visited and
      appeared to affect patients with average health more than others. CONCLUSION:
      Organizational strategies, without resort to differential financial incentives to
      each provider, resulted in lower rates of outpatient services for HMO patients.
      Savings from outpatient use, especially for common diseases that rarely require
      hospitalization, can be substantial.

PMID- 9566180
TI  - Advance care planning in nursing homes: pre- and post-Patient Self-Determination
      Act.
AB  - OBJECTIVES: (1) To identify resident and organizational factors associated with
      the use of advance care plans pre- and post-implementation of the Patient Self
      Determination Act (PSDA), and (2) to identify changes (pre- and post
      implementation of the PSDA) in the relationship between these factors and the use
      of advance care plans. DESIGN: Complex, multistage cluster sampling. SETTING: Ten
      states were selected for variation in geographic location, Medicaid reimbursement
      rate, and average staffing patterns. Participants were 4,215 nursing home
      residents in 268 facilities. PRINCIPAL FINDINGS: Seventeen resident and
      organizational factors were associated with the use of do-not-resuscitate (DNR)
      orders in 1990, and 12 resident and organizational factors were associated with
      their use in 1993. Five factors showed a significant change from 1990 to 1993:
      activities of daily living (ADL) scores, race, cognitive performance scale (CPS)
      scores, full-time equivalent (FTE) nurse aides per resident, and bed size. Ten
      resident and organizational factors were associated with use of do-not
      hospitalize (DNH) orders in 1990 and six resident and organizational factors were
      associated with DNH orders in 1993. Four factors showed a significant change from
      1990 to 1993: legal guardian, FTE LPNs per resident, Medicaid census, and
      forprofit ownership. Five resident and organizational factors were associated
      with the use of living wills in 1990 and seven resident and organizational
      factors were associated with the use of living wills in 1993. Four factors showed
      a significant change from 1990 to 1993: ADL scores, race, length of stay, and for
      profit ownership. CONCLUSION: The results indicate that the PSDA may have been
      successful in increasing the use of advance care plans and in changing the types
      of residents who use advance care plans. However, they also show that the use of
      advance care plans is associated with organizational characteristics, indicating
      that some types of facilities may be more willing and able to address the PSDA
      mandates.

PMID- 9566182
TI  - Advice to coaches of students in one of the youngest sciences.

PMID- 9566181
TI  - A discrete choice model of drug abuse treatment location.
AB  - OBJECTIVE: To identify short-term drug abuse treatment location risk factors for
      ten large, self-insured firms starting January 1, 1989 and ending December 31,
      1991. DATA SOURCES/STUDY SETTING: Study population selected from a large database
      of health insurance claims for all treatment events starting January 1, 1989 and
      ending December 31, 1991. STUDY DESIGN: A nested binomial logit method is used to
      estimate firm-specific patterns of treatment location. The differences in
      treatment location patterns among firms are then decomposed into firm effects
      (holding explanatory variables constant among firms) and variable effects
      (holding firm-specific parameters constant). PRINCIPAL FINDINGS: Probability of
      inpatient drug treatment is directly related to the type of drug diagnosis. The
      most important factors are diagnoses of drug dependence (versus drug abuse)
      and/or a cocaine dependence. Firm-specific factors also make a substantive
      difference. Controlling for patient risk factors, firm-specific probabilities of
      inpatient treatment vary by as much as 87 percent. Controlling for practices of
      firms and their insurance carriers, differing patient risk profiles cause
      probabilities of inpatient treatment to vary by as much as 69 percent among
      firms. Use of the outpatient setting increased over the three-year period.
      CONCLUSIONS: There are two plausible explanations for the findings. First, people
      beginning treatment later in the three-year period had less severe conditions
      than earlier cases and therefore had less need of inpatient treatment. Second,
      drug abuse treatment experienced the same trend toward the increased use of
      outpatient care that characterized treatment for other illnesses in the 1980s and
      early 1990s.

PMID- 9566184
TI  - The rationale for patient cases in the National Board Dental Hygiene
      Examinations.

PMID- 9566185
TI  - Problem-based learning: using cases to drive the learning process.

PMID- 9566186
TI  - An overview of case-based test construction.

PMID- 9566187
TI  - Implementation of an interactive case study on CD-ROM.

PMID- 9566188
TI  - Integrating case-based instruction into dental hygiene curricula.

PMID- 9566189
TI  - Use of case-based learning in dental hygiene curricula.

PMID- 9566190
TI  - The effect of steam sterilization on the physical properties and perceived
      cutting characteristics of extracted teeth.

PMID- 9566191
TI  - Metal ion dependency of microfibrils supports a rod-like conformation for
      fibrillin-1 calcium-binding epidermal growth factor-like domains.
AB  - The effects of the removal and replacement of divalent cations on the
      ultrastructure of 10 to 12 nm fibrillin-1-containing microfibrils have been
      studied, in order to investigate the conformation of fibrillin-1 calcium-binding
      epidermal growth factor-like (cbEGF-like) domains within the microfibril. The NMR
      structure of a covalently linked pair of cbEGF-like domains from fibrillin-1
      recently identified a rigid rod-like conformation for the domain pair stabilised
      by interdomain calcium binding. This suggested that tandem arrays of fibrillin-1
      cbEGF-like domains may adopt an extended conformation within a microfibril. If
      correct, then removal of bound calcium from fibrillin-1 would be expected to
      increase the flexibility of each cbEGF-like interdomain linkage, resulting in a
      decrease in the length of the interbead region of the microfibril (and thus a
      decrease in bead to bead periodicity), a concomitant increase in its diameter,
      and an overall increase in the flexibility of the microfibril. Our results show
      that removal of calcium by treatment with EGTA causes a large alteration of the
      microfibril structure, resulting in microfibrils with a reduced beaded
      periodicity, a disrupted interbead region and an increased overall flexibility.
      These effects are readily reversible by the re-addition of calcium (in the form
      of CaCl2), but not by the addition of magnesium (MgCl2). This is consistent with
      conformational changes in cbEGF-like domains causing the major structural effects
      on the microfibril. These results provide the first direct experimental evidence
      to support an extended rod-like conformation for multiple tandem repeats of
      fibrillin-1 cbEGF-like domains within the microfibril, as predicted by the NMR
      structure of an isolated fibrillin-1 cbEGF-like domain pair.

PMID- 9566192
TI  - On the mechanism of inhibition of phage T7 RNA polymerase by lac repressor.
AB  - We study here the effect on phage T7 RNA polymerase activity of lac repressor
      bound downstream of the T7 promoter. When repressor binds in vitro at an operator
      centered at +13 or +15 with respect to transcription start, it does not prevent
      initiation, though the transcript yield is reduced. However, the processivity of
      the polymerase is depressed and transcript extension is blocked at positions +4
      and +6, respectively. These results indicate that repressor and polymerase do not
      simply exclude each other from the promoter. Rather, they would come into steric
      conflict and compete for establishment or retention of interactions with the same
      segment of DNA, without this leading to the immediate displacement of either
      polymerase or repressor. The resulting destabilization of the transcription
      complex would depress both initiation rate and enzyme processivity. In contrast
      to the above results, little reduction in runoff transcription is observed when
      operator is centered at +47. The decreased sensitivity of polymerase to repressor
      bound at +47 versus +13 or +15 is likely to be due to the higher stability of the
      elongation complex during the transcription of downstream regions in comparison
      with the first transcribed nucleotides. We also show that under conditions of
      leaky repression and with operator centered at +13, a mutant T7 RNA polymerase
      showing normal promoter affinity but a slower elongation rate is more sensitive
      to repression than the wild-type enzyme, both in vitro and in vivo. In vitro,
      this higher sensitivity is largely due to a reduced ability of the mutant to
      overcome the elongation block at position +4. The parallel between the in vitro
      and in vivo data suggests that in vivo the repressor also does not prevent
      polymerase from binding to promoter, but interferes with subsequent steps in
      initiation and transcript extension, in this case presumably largely extension
      beyond +4.

PMID- 9566194
TI  - The activation specificities of wild-type and mutant Gcn4p in vivo can be
      different from the DNA binding specificities of the corresponding bZip peptides
      in vitro.
AB  - Single amino acid substitutions which previously have been shown to alter the DNA
      binding specificity of a Gcn4p bZip peptide in vitro were transformed to full
      length Gcn4p, and activation of a test promoter carrying various palindromic and
      pseudo-palindromic binding sites was measured. All mutations were found to have
      different phenotypes, and the first change-of-specificity mutants for Gcn4p in
      vivo are described. The comparison of plasmids encoding no protein or a
      particular Gcn4p mutant with broadened activation specificity in gcn4 and gcn4
      acr1 genetic backgrounds revealed three new DNA targets of the yeast Acr1p
      repressor. Surprisingly, we found the activation specificities Gcn4p and the
      mutants tested in vivo to be generally different from DNA binding specificities
      of the corresponding bZip peptides in vitro. Especially, the proteins respond
      differently, in vitro and in vivo, on changes in half site spacing of the DNA
      binding sites. We present data which largely exclude that the differences between
      in vivo and in vitro-derived results are due to differences in protein structure,
      or to the presence of competing protein factors in the yeast cell. We conclude
      that the differences between in vitro and in vivo-derived results are caused by
      differences in the degree of flexibility of the target DNA sequences in vitro and
      in vivo.

PMID- 9566193
TI  - The Drosophila melanogaster lipase homologs: a gene family with tissue and
      developmental specific expression.
AB  - We report the molecular cloning of Drosophila genes encoding putative lipase
      homologs, Dm lip1, lip2 and lip3, the definition of their structure and the
      expression patterns during development. These Drosophila lipases are related to
      acid lipases, with a common GHSQG motif, within a more general consensus GXSXG,
      identified as the active site shared by all the members of lipase superfamily.
      The lip1 and lip3 genes are transcribed in different tissues and developmental
      stages, suggesting that they have different functions. The lip1 gene, coding for
      a protein similar to digestive lipases, is expressed in ovaries and early embryos
      and, with a different sized transcript, in all the other developmental stages.
      The lip3 gene, whose translation product is more similar to lysosomal acid
      lipases, is expressed only during the larval period. The lip2 gene seems non
      functional. The Drosophila putative lipases do not show similarity with the
      Drosophila yolk proteins that are reported to have sequence similarity with
      lipoprotein lipases, but share a consistent similarity with lepidopteran proteins
      reported as egg specific or yolk proteins, probably corresponding to lipase
      homologs. The results reported here are discussed in relation to the evolution
      and functions of lipases within the between species.

PMID- 9566195
TI  - Aminoglycoside binding to the hammerhead ribozyme: a general model for the
      interaction of cationic antibiotics with RNA.
AB  - A variety of drugs inhibit biological key processes by binding to a specific RNA
      component. We focus here on the well-analysed hammer-head ribozyme RNA that is
      inhibited by aminoglycoside antibiotics, a process considered as a paradigm for
      studying drug/RNA interactions. With insight gained from molecular dynamics
      simulations of the ribozyme in the presence of Mg2+ identified by crystallography
      and of aminoglycosides in solution, a general model for aminoglycoside binding to
      RNA is proposed. A striking structurally based complementarity between the
      charged ammonium groups of the aminoglycosides and the metal binding sites in the
      hammerhead was uncovered. Despite dynamical flexibility of the aminoglycosides,
      several of the intramolecular distances between the charged ammonium groups of
      the drugs were found to be rather constant. Intramolecular ammonium distances of
      the aminoglycosides span ranges similar to the interionic distances between Mg2+
      in the hammerhead. Successful docking of aminoglycosides to the hammerhead
      ribozyme could be achieved by positioning the ammonium groups at the sites
      occupied by Mg2+. The covalently linked ammonium groups of the aminoglycosides
      are thus able to complement in space the negative electrostatic potential created
      by a three-dimensional RNA fold. Consequently, it is suggested that
      aminoglycoside-derived sugars could constitute a basic set of yardstick synthons
      ideal for rational and combinatorial synthesis of drugs targeted at biologically
      relevant RNA folds.

PMID- 9566196
TI  - Molecular genetic analysis of transposase-end DNA sequence recognition:
      cooperativity of three adjacent base-pairs in specific interaction with a mutant
      Tn5 transposase.
AB  - Transposition of Tn5 and IS50 requires the specific binding of transposase (Tnp)
      to the end inverted repeats, the outside end (OE) and the inside end (IE). OE and
      IE have 12 identical base-pairs and seven non-identical base-pairs. Previously we
      described the isolation of a Tnp mutant, EK54, that shows an altered preference
      for OE versus IE compared to wild-type (wt) Tnp. EK54 enhances OE recognition and
      decreases IE recognition both in DNA binding and in overall transposition. Here
      we report that base-pairs 10, 11 and 12 of the OE are critical for the specific
      recognition by EK54 Tnp. These three adjacent base-pairs act cooperatively; all
      three must be present in order for EK54 Tnp to interact very favorably with the
      end DNA. The existence of only one or two of these three base-pairs decreases
      binding of EK54 Tnp. The combined use of EK54 Tnp and a new OE/IE mosaic end
      sequence containing the OE base-pairs 10, 11 and 12 gives rise to an
      extraordinarily high transposition frequency. Just as the Tnp is a
      multifunctional protein, the nucleotides in the 19 bp Tn5 ends also affect other
      functions besides Tnp binding. Furthermore, the fact that we were able to isolate
      end sequence variants that transpose at a higher frequency than the natural ends
      (OE and IE) with wt Tnp reveals yet another way in which the wt transposition
      frequency is depressed, i.e. by keeping the end sequences suboptimal.

PMID- 9566197
TI  - Structural characterization of a dynein motor domain.
AB  - Cytoplasmic dynein is a microtubule-based mechanochemical protein that plays an
      essential role in cell division, vesicle transport, and cytoplasmic membrane
      organization. As a molecular motor, dynein utilizes an ATP hydrolysis mechanism
      to bind and release microtubules and to undergo conformational changes that
      result in a net displacement towards the microtubule's minus end. To visualize
      structural features of this motor protein, we have begun to characterize the
      dynein head domain by electron microscopy and image processing. Transmission
      electron microscopy of negatively stained native dynein from Dictyostelium has
      been performed and images of the head domain have been aligned and analyzed with
      the software SPIDER. The resulting 2D averages show an oblong round shape
      composed of seven to eight globular domains or lobes that encircle a stain-filled
      area. A recombinant 380 kDa fragment of the dynein heavy chain encodes just the
      globular head domain; analysis of these particles reveals a high structural
      similarity with the native head domain. A prominent stalk can be seen in several
      projections of this fragment, suggesting a structure analogous to the B-link
      described for some axonemal dyneins. Single tilt pair images were used to compute
      low resolution 3D reconstructions of the dynein head domain. These show a
      flattened spheroidal shape of 13.5 nm in length with seven similar domains
      arranged in a ring. Slices through the reconstructions reveal a large central
      cavity. This is the first detailed description of the head domain structure for a
      dynein molecule. The presence of a central cavity and the outer globular
      features, along with its large size make dynein structurally distinct from either
      myosin or kinesin.

PMID- 9566198
TI  - A study of protein side-chain dynamics from new 2H auto-correlation and 13C cross
      correlation NMR experiments: application to the N-terminal SH3 domain from drk.
AB  - Two new NMR experiments are presented for measuring side-chain dynamics in
      proteins. The first method, requiring 15N, 13C, approximately 50% 2H-labeled
      protein, measures 2H T1 and T1p spin relaxation times at side-chain positions. A
      second experiment permits the straightforward measurement of 13C-1H dipole-dipole
      cross-correlation relaxation rates at 13C beta positions in 15N, 13C-labeled
      molecules. An excellent correlation is observed between order parameters,
      describing the amplitude of motion at these sites, obtained on the basis of 2H
      relaxation and dipole-dipole cross-correlation relaxation rates. Together these
      experiments provide a powerful approach for selecting appropriate motional
      models. The methods are applied to study the side-chain motional properties of
      the N-terminal SH3 domain from the signaling protein drk.

PMID- 9566199
TI  - The crystal structure of bikunin from the inter-alpha-inhibitor complex: a serine
      protease inhibitor with two Kunitz domains.
AB  - Bikunin is a serine protease inhibitor found in the blood serum and urine of
      humans and other animals. Its sequence shows internal repetition, suggesting that
      it contains two domains that resemble bovine pancreatic trypsin inhibitor (BPTI).
      A fragment of bikunin has been crystallised, its structure solved and
      subsequently refined against 2.5 A data. The two BPTI-like domains pack closely
      together and are related by an approximate 60 degrees rotation combined with a
      translation. These domains are very similar to each other and other proteins with
      this fold. The largest variations occur in the loops responsible for protease
      recognition. The loops of the first domain are unobstructed by the remaining
      protein. However, the loops of the second domain are close to the first domain
      and it is possible that protease binding may be affected or, in some cases,
      abolished by the presence of the first domain. Thus, cleavage of the two domains
      could alter the substrate specificity of domain II. Bikunin has a hydrophobic
      patch close to the N terminus of domain I, which is the most likely site for cell
      surface receptor binding. In addition, there is a basic patch at one end of
      domain II that may be responsible for the inhibition of calcium oxalate
      crystallization in urine.

PMID- 9566200
TI  - Primary chemotherapy for breast cancer: hope or hype?

PMID- 9566201
TI  - Indications for neoadjuvant chemotherapy for breast cancer.

PMID- 9566202
TI  - Breast-conserving surgery in the neoadjuvant setting.
AB  - The use of neoadjuvant chemotherapy for the treatment of patients with operable
      breast cancer remains controversial. Neoadjuvant chemotherapy is highly effective
      in achieving significant tumor regression. However, the primary goal of improved
      survival has yet to be clearly demonstrated. The largest prospective trial with
      adequate follow-up to report 5-year disease-free survival data demonstrated no
      significant difference between patients treated with neoadjuvant chemotherapy
      followed by locoregional treatment and locoregional treatment followed by
      adjuvant chemotherapy. Survival data from the National Surgical Adjuvant Breast
      and Bowel Project B-18 trial are not yet available. The potential impact on the
      breast conservation rate for patients with early operable breast cancer is small,
      and careful follow-up of the long-term risk of local recurrence for patients with
      neoadjuvant therapy induced downstaging followed by BCT is not yet available. At
      this time, neoadjuvant chemotherapy for the treatment of patients with operable
      breast cancer should be considered investigational.

PMID- 9566203
TI  - Molecular and biologic determinants of neoadjuvant chemotherapy of locoregional
      breast cancer.

PMID- 9566204
TI  - Primary chemotherapy regimens and schedules.

PMID- 9566205
TI  - Overview of National Surgical Adjuvant Breast Project neoadjuvant chemotherapy
      studies.

PMID- 9566206
TI  - Future direction of neoadjuvant therapy for breast cancer.

PMID- 9566207
TI  - Physical factors influencing the oviposition of Lutzomyia migonei (Diptera:
      Psychodidae) in laboratory conditions.
AB  - To determine the influence of physical factors on oviposition of Lutzomyia
      migonei (Diptera: Psychodidae) under laboratory conditions, two sets of
      experiments were performed. The first test was to determine the influence of the
      size of pots on oviposition. Gravid flies were placed individually or in groups
      in different oviposition pots. The number of eggs laid, oviposition time and
      survival of gravid females were observed. In the second experiment, the influence
      of irregular surfaces on oviposition was studied. The results suggested that
      physical space was not an important factor in the oviposition behavior of L.
      migonei and that the flies showed a preference to oviposit on irregular
      horizontal surfaces in response to thigmotropic behavior.

PMID- 9566208
TI  - The influence of self-fertilization performance and copulation behaviour in
      reproduction by cross-fertilization in groups of Biomphalaria tenagophila
      (Mollusca, Planorbidae).
AB  - The following hypotheses were tested for groups of simultaneous hermaphrodites
      Biomphalaria tenagophila: (a) snails that have low reproductive success during
      the process of self-fertilization do not increase their reproductive success
      after the end of grouping; (b) the copulation behaviour and the presence of one
      snail whose eggs have a low viability rate influence the partner's reproductive
      success by cross-fertilization. Groups were constituted by a homozygous pigmented
      snail and two albinos: one with a viability rate higher than 70% ("good
      reproducers") and the other less than 10% ("bad reproducers"). All pigmented
      snails had viability rates higher than 70%. The "good" and "bad" reproducer
      albino snails had similar copulation behaviour. However, after the end of
      grouping, the "bad reproducers" continued to have viability rates less than 10%
      over 30 days. In 100% of the cases that pigmented snails copulated (performing
      either a male role or simultaneously male and female roles) exclusively with
      "good" reproducer albinos, they presented high reproductive success (producing,
      on average of 8.4 pigmented embryos/egg-mass). However, in 100% of the cases that
      pigmented snails copulated with both partners, the "good" reproducer albino
      snails produced none or very few embryos (the highest average was 2.2 pigmented
      embryos/egg-mass). Therefore, the production of viable embryos by cross
      fertilization was more influenced by self-fertilization performance than by
      copulation behaviour. The presence of a snail whose eggs have a low viability
      rate could decrease their partners reproductive success.

PMID- 9566209
TI  - Detection of Toxoplasma gondii-specific antibodies in dogs. A comparative study
      of immunoenzymatic, immunofluorescent and haemagglutination titers.
AB  - We evaluated the titers of anti-T. gondii antibodies by various serological tests
      in 40 serum samples from dogs exhibiting clinical signs of infectious diseases.
      Indirect immunofluorescence (IgG-IFI), indirect haemagglutination (IHA and M
      Toxo) and immunoenzymatic (ELISA and PA-ELISA) tests were carried out. Titers >
      or = 64 were considered as positive. Anti-Toxoplasma antibodies were found in 9
      (22.5%), 14 (35%), 14 (35%) and 12 (30%) samples, respectively for IHA, IgG-IFI,
      ELISA and PA-ELISA. The results showed that 57% were negative in all tests and
      43% of the dogs presented antibodies to T. gondii; from these, 20% were positive
      in all three tests with high titers of antibodies and 23% were positive in only
      one or two tests with low titers of antibodies and mainly related to the IFI and
      ELISA tests. We observed 5 (12.5%) and 1 (2.5%) reactive samples, respectively,
      by M-Toxo and IHA with or without 2-mercapthoethanol, in the attempt to detect
      specific IgM. We can conclude that serodiagnosis of toxoplasmosis in dog have to
      be based on the combination of serological tests (IFI and ELISA) and with
      emphasis at the determination of the titers and the classes of the specific
      antibodies.

PMID- 9566210
TI  - Differential serodiagnosis of human infections caused by Trypanosoma cruzi and
      Leishmania spp. using ELISA with a recombinant antigen (rTc24).

PMID- 9566211
TI  - Cell growth inhibitor factor in hemolymph of Dipetalogaster maximus.

PMID- 9566212
TI  - Induction of glutathione S-transferase activity in Triatoma infestans.
AB  - Several synthetic pesticides and allelochemicals used to treat Triatoma infestans
      adults by topic application showed some degree of cytosolic glutathione S
      transferase (GST) induction. General inducers of detoxication systems such as
      phenobarbital and 3-methylcholantrene topically applied on T. infestans resulted
      in no GST induction. Meanwhile, general insecticide synergist such as piperonyl
      butoxide (160 micrograms/insect) increased the GST-activity in the range of 120
      140%. Insects injected with reduced glutathione (300 mg/insect) presented at the
      forth day elevated GST activity.

PMID- 9566213
TI  - Biological parameters and molecular markers of clone CL Brener--the reference
      organism of the Trypanosoma cruzi genome project.
AB  - Clone CL Brener is the reference organism used in the Trypanosoma cruzi Genome
      Project. Some biological parameters of CL Brener were determined: (a) the
      doubling time of epimastigote forms cultured in liver infusion-tryptose (LIT)
      medium at 28 degrees C is 58 +/- 13 hr; (b) differentiation of epimastigotes to
      metacyclic trypomastigotes is obtained by incubation in LIT-20% Grace's medium;
      (c) trypomastigotes infect mammalian cultured cells and perform the complete
      intracellular cycle at 33 and 37 degrees C; (d) blood forms are highly infective
      to mice; (e) blood forms are susceptible to nifurtimox and benznidazole. The
      molecular typing of CL Brener has been determined: (a) isoenzymatic profiles are
      characteristic of zymodeme ZB; (b) PCR amplification of a 24S alpha ribosomal RNA
      sequence indicates it belongs to T. cruzi lineage 1; (c) schizodeme, randomly
      amplified polymorphic DNA (RAPD) and DNA fingerprinting analyses were performed.

PMID- 9566214
TI  - Separation and mapping of chromosomes of parasitic protozoa.
AB  - Many protozoan parasites represent an important group of human pathogens. Pulsed
      Field Gradient Gel Electrophoresis (PFGE) analysis has been an important tool for
      fundamental genetic studies of parasites like Trypanosoma, Leishmania, Giardia or
      the human malaria parasite Plasmodium falciparum. We present PFGE conditions
      allowing a high resolution separation of chromosomes ranging from 500 to 4000 kb
      within a two day electrophoresis run. In addition, we present conditions for
      separating large chromosomes (2000-6000 kb) within 36 hr. We demonstrate that the
      application of two dimensional PFGE (2D-PFGE) technique to parasite karyotypes is
      a very useful method for the analysis of dispersed gene families and comparative
      studies of the intrachromosomal genome organization.

PMID- 9566215
TI  - Proceedings of the schistosome genome project.
AB  - "The host-parasite relationship" is a vast and diverse research field which,
      despite huge human and financial input over many years, remains largely shrouded
      in mystery. Clearly, the adaptation of parasites to their different host species,
      and to the different environmental stresses that they represent, depends on
      interactions with, and responses to, various molecules of host and/or parasite
      origin. The schistosome genome project is a primary strategy to reach the goal;
      this systematic research project has successfully developed novel technologies
      for qualitative and quantitative characterization of schistosome genes and genome
      organization by extensive international collaboration between top quality
      laboratories. Schistosomes are a family of parasitic blood flukes (Phylum
      Platyhelminthes), which have seven pairs of autosomal chromosomes and one pair of
      sex chromosomes (ZZ for a male worm and ZW for a female), of a haploid genome
      size of 2.7 x 10(8) base pairs (Simpson et al. 1982). Schistosomes are ideal
      model organisms for the development of genome mapping strategies since they have
      a small genome size comparable to that of well-characterized model organisms such
      as Caenorhabditis elegans (100 Mb) and Drosophila (165 Mb), and contain
      functional genes with a high level of homology to the host mammalian genes. Here
      we summarize the current progress in the schistosome genome project, the
      information of 3,047 transcribed genes (Expressed Sequence Tags; EST), complete
      sets of cDNA and genomic DNA libraries (including YAC and cosmid libraries) with
      a mapping technique to the well defined schistosome chromosomes. The schistosome
      genome project will further identify and characterize the key molecules that are
      responsible for host-parasite adaptation, i.e., successful growth, development,
      maturation and reproduction of the parasite within its host in the near future.

PMID- 9566216
TI  - Compositional constraints in the extremely GC-poor genome of Plasmodium
      falciparum.
AB  - We have analyzed the compositional properties of coding (protein encoding) and
      non-coding sequences of Plasmodium falciparum, a unicellular parasite
      characterized by an extremely AT-rich genome. GC% levels, base and dinucleotide
      frequencies were studied. We found that among the various factors that contribute
      to the properties of the sequences analyzed, the most relevant are the
      compositional constraints which operate on the whole genome.

PMID- 9566217
TI  - Towards the physical map of the Trypanosoma cruzi nuclear genome: construction of
      YAC and BAC libraries of the reference clone T. cruzi CL-Brener.
AB  - Strategies to construct the physical map of the Trypanosoma cruzi nuclear genome
      have to capitalize on three main advantages of the parasite genome, namely (a)
      its small size, (b) the fact that all chromosomes can be defined, and many of
      them can be isolated by pulse field gel electrophoresis, and (c) the fact that
      simple Southern blots of electrophoretic karyotypes can be used to map sequence
      tagged sites and expressed sequence tags to chromosomal bands. A major drawback
      to cope with is the complexity of T. cruzi genetics, that hinders the
      construction of a comprehensive genetic map. As a first step towards physical
      mapping, we report the construction and partial characterization of a T. cruzi CL
      Brener genomic library in yeast artificial chromosomes (YACs) that consists of
      2,770 individual YACs with a mean insert size of 365 kb encompassing around 10
      genomic equivalents. Two libraries in bacterial artificial chromosomes (BACs)
      have been constructed, BACI and BACII. Both libraries represent about three
      genome equivalents. A third BAC library (BAC III) is being constructed. YACs and
      BACs are invaluable tools for physical mapping. More generally, they have to be
      considered as a common resource for research in Chagas disease.

PMID- 9566218
TI  - Genes and chromosomes of Leishmania infantum.
AB  - During recent years, several Leishmania infantum genes have been cloned and
      characterized. Here, we have summarized the available information on the gene
      organization and expression in this protozoan parasite. From a comparative
      analysis, the following outstanding features were found to be common to most of
      the genes characterized: tandemly organized genes with conserved coding regions
      and divergent untranslated regions, polycistronic transcription and post
      transcriptional regulation of gene expression. The analysis of chromosomes of L.
      infantum by pulsed-field electrophoresis showed the existence of both size and
      number polymorphisms such that each strain has a distinctive molecular karyotype.
      Despite this variability, highly conserved physical linkage groups exists among
      different strains of L. infantum and even among Old World Leishmania species.
      Gene mapping on the L. infantum molecular karyotype evidenced a bias in
      chromosomal distribution of, at least, the evolutionary conserved genes.

PMID- 9566219
TI  - Parasite genome projects and the Trypanosoma cruzi genome initiative.
AB  - Since the start of the human genome project, a great number of genome projects on
      other "model" organism have been initiated, some of them already completed.
      Several initiatives have also been started on parasite genomes, mainly through
      support from WHO/TDR, involving North-South and South-South collaborations, and
      great hopes are vested in that these initiatives will lead to new tools for
      disease control and prevention, as well as to the establishment of genomic
      research technology in developing countries. The Trypanosoma cruzi genome
      project, using the clone CL-Brener as starting point, has made considerable
      progress through the concerted action of more than 20 laboratories, most of them
      in the South. A brief overview of the current state of the project is given.

PMID- 9566220
TI  - Epidemiological characteristics of Schistosoma mansoni infection in rural and
      urban endemic areas of Minas Gerais, Brazil.
AB  - To compare the epidemiological profile and socioeconomic factors associated to
      the infection by Schistosoma mansoni in a rural and an urban endemic area a cross
      sectional study was performed in Agua Branca de Minas (rural area) and Bela Fama
      (urban area), both situated in the State of Minas Gerais, Brazil. Two hundred and
      eighty eight individuals were surveyed in the rural area and 787 in the urban
      area. Water contact and socioeconomic questionnaires were used to identify risk
      factors for the infection. The prevalences of 38.8% and 9.7% and the geometric
      mean of eggs per gram of faeces of 117.8 and 62.3 were found in the rural and
      urban areas, respectively. By multivariate statistical analysis age groups over
      nine years old and previous specific treatment were associated with the infection
      in rural area. In urban area age over nine years old, low quality housing, weekly
      fishing and swimming were associated after adjustment by logistic regression.

PMID- 9566221
TI  - Cutaneous leishmaniasis in Venezuela caused by infection with a new hybrid
      between Leishmania (Viannia) braziliensis and L. (V.) guyanensis.

PMID- 9566222
TI  - Detection of sylvatic dark morphs of Triatoma infestans in the Bolivian Chaco.

PMID- 9566223
TI  - Comparison between two methods for diagnosis of trichinellosis: trichinoscopy and
      artificial digestion.
AB  - Two direct methods for the diagnosis of trichinellosis were compared:
      trichinoscopy and artificial digestion. Muscles from 17 wistar rats, orally
      infected with 500 Trichinella spiralis encysted larvae were examined. From each
      of the following muscles: diaphragm, tongue, masseters, intercostals, triceps
      brachialis and cuadriceps femoralis, 648,440 larvae from 1 g samples were
      recovered. The linear correlation between trichinoscopy and artificial digestion
      was very high and significant (r = 0.94, p < 0.0001), showing that both methods
      for the detection of muscular larvae did not differ significantly. In both
      methods, significant differences were found in the distribution of larvae per
      gramme of muscle.

PMID- 9566224
TI  - Toxoplasma gondii antigenuria in patients with acquired immune deficiency
      syndrome.
AB  - A longitudinal study was performed with sera and urine of patients with acquired
      immune deficiency syndrome (AIDS), taken before, during and after clinically
      Toxoplasma infection. The tested patients were followed for an average of two
      years. The titres of the specific IgG and IgM antibodies were measured by an
      indirect fluorescent antibody test (IFAT), and the appearance of circulating
      antigens of T. gondii was determined in 36 urine samples of 13 patients with
      neurotoxoplasmosis by means of the coagglutination test. The presence of T.
      gondii antigens in the urine of AIDS patients by this test was correlated with
      the immunoblot technique, with clinical symptoms and also with pathological
      findings. Our results indicate that the detection of T. gondii antigens in the
      urine of AIDS patients can be regarded as a rapid and efficient method for the
      diagnosis of acute toxoplasmosis.

PMID- 9566225
TI  - Diagnosis of dengue by using reverse transcriptase-polymerase chain reaction.
AB  - A rapid identification of dengue viruses from clinical samples by using a nested
      reverse transcriptase-polymerase chain reaction (RT-PCR) procedure was carried
      out for diagnostic and epidemiological purposes. RT-PCR identified DEN-1 and DEN
      2 viruses in 41% (41/100) of previously confirmed cases and provided an accurate
      confirmation of DHF in four fatal cases. RT-PCR was also useful for detecting and
      typing dengue viruses in suspected cases, allowing a rapid identification of new
      serotypes in endemic areas.

PMID- 9566226
TI  - Sensitivity of Leishmania spp. to glibenclamide and 4-aminopyridine: a tool for
      the study of drug resistance development.
AB  - We have demonstrated that Leishmania spp. grown as promastigotes, are sensitive
      to the K+ channel inhibitors 4-aminopyridine and glibenclamide. Their host cells,
      the macrophages, are not affected by similar concentrations of the drugs. We have
      also initiated the molecular characterization of the mechanisms involved in the
      development of drug resistance to glibenclamide by the parasite. Therefore, we
      have selected experimentally and begun to characterize the Venezuelan Leishmania
      (Leishmania) strain, NR resistant to glibenclamide [NR(Gr)]. The analysis of
      genomic DNA evidenced the existence of a fragment which apparently is amplified
      in NR(Gr). The fragment recognized by the pgpA probe, related to the Leishmania P
      glycoprotein family and which was originally isolated from L. tarentolae, showed
      a size polymorfism between the sensitive and the resistant strain. These results
      suggest that the development of resistance to glibenclamide in the strain NR(Gr)
      might be associated with the amplification of the ltpgpA or related gene(s).

PMID- 9566227
TI  - The role of protein kinases in antigen-activation of peripheral blood mononuclear
      cells of Schistosoma mansoni infected individuals.
AB  - T cell recognition of antigens displayed on the surface of antigen presenting
      cell results in rapid activation of protein tyrosine kinases and kinase C. This
      process leads to second messengers, such as inositol phosphates and
      diacylgycerol, and phosphorylation of multiple proteins. The role of different
      protein kinases in the activation of peripheral blood mononuclear cells (PBMC)
      from Schistosoma mansoni infected individuals was evaluated using genistein and H
      7, specific inhibitors of protein tyrosine kinase and kinase C, respectively. Our
      results showed that proliferation in response to soluble egg antigen or adult
      worm antigen preparation of S. mansoni was reduced when PBMC were cultured in
      presence of protein kinase inhibitors. Using these inhibitors on in vitro
      granuloma reaction, we also observed a marked reduction of granuloma index. Taken
      together, our results suggest that S. mansoni antigen activation of PBMC involves
      protein kinases activity.

PMID- 9566228
TI  - Effects of Bayluscide WP 70 on the survival and water-leaving behaviour of
      Biomphalaria straminea, snail host of schistosomiasis in northeast Brazil.
AB  - The toxic and behavioural effects of niclosamide (Bayluscide WP 70) on
      Biomphalaria straminea from a highly endemic area of schistosomiasis in
      northeastern Brazil were investigated through laboratory bioassays. The LD50 and
      LD90 were 0.114 mg/l and 0.212 mg/l, respectively. Water-leaving behaviour
      occurred among 14% to 30% of the snails in the presence of sublethal doses of
      niclosamide and among 16% of the controls. It was concluded that both the
      relatively low susceptibility to niclosamide and water-leaving behaviour of local
      B. straminea may be responsible for the recolonization of transmission foci after
      mollusciciding. It was suggested that recently improved measures of snail
      control, such as controlled-release formulations of niclosamide and plant
      molluscicides should be considered in areas where snail control is recommended.

PMID- 9566229
TI  - Update of the gene discovery program in Schistosoma mansoni with the expressed
      sequence tag approach.
AB  - Continuing the Schistosoma mansoni Genome Project 363 new templates were
      sequenced generating 205 more ESTs corresponding to 91 genes. Seventy four of
      these genes (81%) had not previously been described in S. mansoni. Among the
      newly discovered genes there are several of significant biological interest such
      as synaptophysin, NIFs-like and rho-GDP dissociation inhibitor.

PMID- 9566230
TI  - Acute schistosomiasis: report on five singular cases.
AB  - The cases of five patients with unusual manifestations of acute schistosomiasis
      mansoni are described in this paper. One patient developed skin lesions, three
      displayed diverse lung involvement, and one presented pyogenic liver abscesses
      caused by Staphylococcus aureus.

PMID- 9566231
TI  - Expression of recombinant antigens in Escherichia coli: application on
      immunochemical studies of Schistosoma mansoni tegumental antigens.
AB  - Sm15 and Sm13 are recognized by antibodies from mice protectively vaccinated with
      tegumental membranes, suggesting a potential role in protective immunity. In
      order to raise antibodies for immunochemical investigations, the genes for these
      antigens were expressed in pGEX and pMal vectors so that comparisons could be
      made among different expression systems and different genes. The fusion proteins
      corresponding to several parts of the gene for the precursor of Sm15 failed in
      producing antibodies recognizing the parasite counterpart. On the other hand,
      antibodies raised against Sm13 MBP-fusion proteins recognized the 13 kDa
      tegumental protein. Thus the peculiarities of the gene of interest are important
      and the choice of the expression system must sometimes be decided on an empirical
      basis.

PMID- 9566232
TI  - Cloning and characterization of a Schistosoma mansoni cDNA clone with a specific
      antigenic expression during development in a vertebrate host.
AB  - Approximately 2.0 x 10 cDNA clones of an Schistosoma mansoni lambda gt11 cDNA
      library were screened in duplicate with serum from infected mice corresponding to
      distinct phases of infection. A cDNA clone (7/1) was isolated and recognized only
      by seven week serum. The clone was subcloned in pGEX-2T and Western-blot studies
      showed a specific antigenic expression confirming that only serum from the
      chronic phase is capable of recognizing this antigen. Dot-hybridization with RNA
      from different developmental phases of the parasite showed that the corresponding
      7/1 RNA is expressed in all phases of parasite development in vertebrate hosts.

PMID- 9566233
TI  - Morphological study of adult male worms of Schistosoma mansoni Sambon, 1907 by
      scanning electron microscopy.
AB  - Tubercles, spines and sensory receptors are the most studied structures of adult
      male worms of Schistosoma mansoni isolated in other countries. The purpose of
      this investigation was to properly define these structures in Brazilian worms.
      Specimens 7-8 weeks after infection were recovered from albino SW mice and from a
      wild rodent (Nectomys squamipes) and processed for scanning electron microscopy
      studies. Photomicrographs of the anterior region with the aspects related to the
      outer and inner regions of both suckers were considered. The ventral portion of
      the middle region was represented by the anterior of gynaecophoric canal while
      the dorsal surface was studied in its ventral and dorsal regions mainly focusing
      the aspect of the tubercles, spines and sensorial papillae. The outer surface of
      the oral sucker is spiny and spines are bigger, sharp with sensory receptors in
      their posterior edge. Tubercles with spines or receptors are more concentrated in
      the middle region and in one of the margins of the gynaecophoric canal. An
      excretory pore-like structure in the posterior portion was observed. The
      gynaecophoric canal has few sensory structures, spines broadened in their mid
      region and are sharp pointed at the distal end. It was concluded that the
      presently studied characters are similar to those previously reported.

PMID- 9566234
TI  - Antigenic recognition pattern of schistosomiasis patients bearing different
      parasite burdens.

PMID- 9566235
TI  - Photodegradation of the molluscicidal latex of "crown-of-thorns" (Euphorbia milii
      var hislopii).

PMID- 9566236
TI  - A laboratory-based approach to biological control of snails.
AB  - Development of Schistosoma mansoni in the intermediate host Biomphalaria glabrata
      is influenced by a number of parasite and snail genes. Understanding the genetics
      involved in this complex host/ parasite relationship may lead to an often
      discussed approach of introducing resistant B. glabrata into the field as a means
      of biological control for the parasite. For the snail, juvenile susceptibility to
      the parasite is controlled by at least four genes, whereas one gene seems to be
      responsible for adult nonsusceptibility. Obtaining DNA from F2 progeny snails
      from crosses between parasite-resistant and -susceptible snails, we have searched
      for molecular markers that show linkage to either the resistant or susceptible
      phenotype. Both restriction fragment length polymorphism (RFLP) and random
      amplified polymorphic DNA (RAPD) approaches have been used. To date, using a
      variety of snail and heterologous species probes, no RFLP marker has been found
      that segregates with either the resistant or susceptible phenotype in F2 progeny
      snails. More promising results however have been found with the RAPD approach,
      where a 1.3 kb marker appears in nearly all resistant progeny, and a 1.1 kb
      marker appears in all susceptible progeny.

PMID- 9566237
TI  - Evidentiation of paramyosin (Sm-97) as a modulating antigen on granulomatous
      hypersensitivity to Schistosoma mansoni eggs.
AB  - A Schistosoma mansoni adult worm anionic fraction (PIII) has previously been
      shown to protect mice against challenge infection and to reduce pulmonary and
      hepatic granulomatous hypersensitivity. Serum from PIII-immunized rabbit was used
      to screen a lambda gt11 cDNA library from S. mansoni adult worm in order to
      identify antigens capable of modulating granulomatous hypersensitivity. We
      obtained four clones with 400 (Sm-III.11), 900 (Sm-III.16), 1100 (Sm-III.10) and
      1300 (Sm-III.12) bp of length. All clone-specific antibodies were able to
      recognize most of the PIII components. The sequence analysis showed that these
      clones presented high homology with S. mansoni paramyosin (Sm-97). These findings
      ascribe a new function to this antigen with an important role in modulation of
      granulomatous hypersensitivity to S. mansoni eggs.

PMID- 9566238
TI  - Diagnosing schistosomiasis.
AB  - The ideal diagnostic method for schistosomiasis detection seems to be still far
      from available. Paucity of egg output in low prevalence situations, low levels of
      circulating antigens in individuals with low intensity of infection and
      inadequate specificity of antibody detection systems outline pieces of a puzzle
      that challenges scientific efforts. Estimated prevalence, financial resources and
      operational reality must be taken into account when deciding the diagnostic
      method to be used. A combination of a screening step, using a fast strip test for
      antibody detection with a parasitological ratification step such as Kato-Katz
      repeated stool examination may serve as a diagnostic approach for a previously
      untreated low level endemic area. However, when eradication is the aim, and high
      financial investment is available, re-treatment may be based on the association
      between multiple stool examination and circulating antigen detection. Ethical
      aspects as well as cost-benefit rates between treatment and diagnosis approaches
      lead to the conclusion that in spite of the recent advances in simple
      administered and relatively safe drugs, treatment should only be performed when
      supported by appropriated diagnosis.

PMID- 9566239
TI  - Role of immune complexes from patients with different clinical forms of
      schistosomiasis in the modulation of in vitro granuloma research.
AB  - Schistosomiasis is a disease whose pathology is strongly related to the
      granulomatous reaction formed around parasite eggs trapped in host tissues.
      Studies have shown that the chronic intestinal form (INT) of this infection is
      associated with a variety of immunoregulatory mechanisms which lead to a
      diminished granulomatous reaction. Using an in vitro model of granuloma reaction,
      we show that immune complexes (IC) isolated from sera of INT patients are able to
      reduce granulomatous reaction developed by peripheral blood mononuclear cells
      (PBMC) from acute (AC), INT and hepatosplenic (HE) patients to soluble egg
      antigen (SEA)-conjugated polyacrylamide beads (PB-SEA). This inhibitory activity
      is also observed in cell proliferation assay of PBMC from INT and HE patients
      stimulated with SEA and adult worm antigen (SWAP). Furthermore, IC isolated from
      sera of patients with different clinical forms of the disease are also able to
      suppress INT patients PBMC reactivity. Therefore, our results show that
      circulating IC present in sera of patients with different clinical forms of
      schistosomiasis may downregulate PBMC reactivity to parasite antigens resulting
      in a diminished granuloma reaction to parasite eggs.

PMID- 9566240
TI  - Differential regulation of granuloma size and hepatic fibrosis in schistosome
      infections.
AB  - Granuloma size is the variable most frequently used to evaluate the
      immunopathogenesis of schistosome infections. However, hepatic fibrosis is at the
      least an equally relevant variable. Hepatic fibrosis and the size of circumoval
      granulomas are frequently dissociated in experimental murine Schistosoma mansoni
      and S. japonicum infections. Virtually nothing is known of the immunoregulation
      of schistosomal hepatic fibrosis. This review notes many of the studies which
      have found discrepancies in granuloma volume and hepatic fibrosis, attempts to
      put them in perspective and to evaluate different methods of calculating changes
      in collagen synthesis or content.

PMID- 9566241
TI  - Impact of antifibrotic treatment of the course of Schistosoma mansoni infection
      in murine model.
AB  - Administration of an antifibrotic agent as an adjunct to antihelmintic treatment
      with the objective of morbidity reduction was investigated in the murine
      schistosomiasis mansoni model. Antifibrotic, beta-aminopropionitrile treatment
      has a profound effect on the cellular matrix composition of the liver granuloma
      of Schistosoma mansoni infected mice when given alone, resulting in increase
      macrophage infiltration. These macrophages, in response to stimulation with
      soluble egg antigen or lipopolysaccharide produced elevated levels of nitric
      oxide but low levels of tumor necrosis factor alpha compared to untreated
      infected mice. This also correlated with reduced liver granuloma size. In spite
      of low numbers of eggs in the liver, mice receiving a combine treatment had a
      high level of resistance to a challenge infection compared with mice receiving
      only praziquantel. Those mice also exhibited a reduced lymphocyte proliferative
      response, similar to that of infected untreated mice. Antifibrotic treatment has
      an impact on the dynamic of the cellular nature of granulomas and impacts on the
      host immunity of infection.

PMID- 9566242
TI  - An experimental approach to the pathogenesis of "pipestem" fibrosis (Symmers'
      fibrosis of the liver).
AB  - Pathogenesis of schistosomal hepatic fibrosis ("pipestem" fibrosis of the liver)
      was investigated by means of the murine model. Although worm load appears as the
      main pathogenetic factor, alone it is not sufficient to produce that
      characteristic lesion. By comparing the findings in animals with heavy and
      prolonged Schistosoma mansoni infection, which developed or not "pipestem"
      fibrosis, it was observed that the lesion was more frequent in intact animals
      than in the splenectomized one. However, the size of the spleen, the number of
      recovered worms, the number of eggs per gram of liver tissue, the level of serum
      idiotype and anti-idiotype antibodies, the size and volume of periovular
      granulomas formed in the liver, all that failed to show statistically significant
      differences between the two groups. After analysing all these data, other
      factors, that apparently have been hitherto negleted, rested to explain the
      findings. Among them, the timing and sequence of the egg-induced intrahepatic
      vascular changes seemed crucial. The sequential development of intrahepatic
      portal vein obstruction, followed by the opening of periportal collateral veins
      and the continous arrival of schistosome eggs going to be lodged into the latter,
      appeared as essential steps in the pathogenesis of "pipestem" fibrosis.

PMID- 9566243
TI  - Factors involved in Schistosoma mansoni infection in rural areas of northeast
      Brazil.
AB  - Two contiguous villages in Tracunhaem county (State of Pernambuco), endemic for
      schistosomiasis, were studied: Itapinassu (138 inhabitants) and Sao Joaquim (91
      inhabitants). Agriculture predominates in the former region while ceramics is the
      main activity in the latter. Although no statistical difference was found
      regarding prevalence, severe infection (> 400 epg) predominated in Itapinassu,
      probably related to the kind of occupation. No association was found between
      parasite burden and severity of disease, in spite of the high infection rates for
      Schistosoma mansoni in both communities (approx. 60%). Typical epidemiological
      features of schistosomiasis such as age-related prevalences and intensities of
      infection (high in children, low in adults) were also mutual characteristics.
      Nutritional status determined through anthropometric evaluation was carried out
      by measuring specific anthropometric indicators. A deficit of energy intake, as
      well as vitamin A and riboflavin deficiencies were detected. The prevalence of
      moderate or severe undernutrition in patients under 18 years old was 21.9% in
      Itapinassu and 24.1% in Sao Joaquim. In this group an association was found
      between prevalence of schistosomiasis and chronic undernutrition. Similarly, for
      patients over 18 year old the prevalence of undernutrition was higher than 20%.
      However, in this case no association between nutritional status and either
      prevalence of schistosomiasis or parasite burden could be detected. The two
      communities had not been treated for eight years.

PMID- 9566244
TI  - Paleoparasitology of schistosomiasis.

PMID- 9566245
TI  - Evaluation of the molluscicidal properties of Euphorbia splendens var. hislopii
      (N.E.B.) latex: experimental test in an endemic area in the State of Minas
      Gerais, Brazil.
AB  - Following the positive results obtained regarding the molluscicidal properties of
      the latex of Euphorbia splendens that were corroborated in laboratory and field
      tests under restricted conditions, a field study was conducted in experimental
      streams located in an endemic area. After recording the average annual
      fluctuations of vectors in three streams, a solution of E. splendens latex at 12
      ppm was applied in stream A, a solution of niclosamide at 3 ppm that was applied
      in stream B and a third stream (C) remained untreated for negative control.
      Applications of E. splendens and niclosamide resulted in a mortality of 100%
      among the snails collected in the streams A and B. No dead snails were found in
      the negative control stream. A monthly follow-up survey conducted during three
      consecutive months confirmed the return of vectors to both experimental streams
      treated with latex and niclosamide. This fact has called for a need to repeat
      application in order to reach the snails that remained buried in the mud
      substrate or escaped to the water edge, as well as, newly hatched snails that did
      not respond to the concentration of these molluscicides. Adults snails collected
      a month following treatment led us to believe that they had migrate from
      untreated areas of the streams to those previously treated.

PMID- 9566246
TI  - The WHO Collaborating Centre for Research and Control of Schistosomiasis at
      Niamey, Niger.
AB  - The Centre de Recherche sur les Meningites et les Schistosomes (CERMES) is a
      research institute depending on the Organisation de Coordination et de
      Cooperation pour la lutte contre les Grandes Endemies--a West African
      Organization for Public Health--devoted to the studies on schistosomiasis and
      meningitis. The staff includes 32 persons with 11 scientists and one financial
      officer. The activities of the CERMES involving schistosomiasis concern three
      research units: (a) ecology of human and animal schistosomiasis transmission; the
      CERMES defined the different patterns of schistosomiasis transmission in Niger
      (involving African dry savana); in this field, we have shown, (i) the existence
      of important variability in conditions of transmission of S. haematobium and,
      (ii) natural hybridization between parasitic species of the ruminants (S. bovis
      and S. curassoni) and genetic interaction between human and animal parasites; (b)
      definition of morbidity indicators usable for rapid assessment methods, for
      appraisal of the severity of the disease and for the evaluation of the efficiency
      of control methods; we have established the correlation between ultrasonographic
      data and some cheap and simple field indicators; (c) immune response and
      protective immunity induced by recombinant glutathion S-transferase (Sm28, Sb28
      and Sh28) in homologous and heterologous animal models including goats, sheep and
      non human primates (Erythrocebus patas). In Niger, we participate in all control
      programs against schistosomiasis to define control strategies, to supervise
      operations and to participate in their evaluation with external experts.
      International collaborations constitute a frame including four laboratories in
      Africa and six laboratories in developed countries (Europe and USA).

PMID- 9566247
TI  - [Structural and functional dynamics of DNA and RNA polymerases].

PMID- 9566248
TI  - [Alternatives in molecular biology].

PMID- 9566249
TI  - [Molecular mechanisms of "protein heredity": yeast prions].

PMID- 9566250
TI  - [New approaches to studying the structural-functional organization of eukaryotic
      genome].

PMID- 9566251
TI  - [Perseverance of viruses].

PMID- 9566252
TI  - [Chemical ribonucleases].

PMID- 9566253
TI  - [Presenilins: detection and characterization of Alzheimer's disease genes].

PMID- 9566254
TI  - [Alu elements in human genome. Invariant secondary structure of left and right
      monomers].

PMID- 9566255
TI  - [Kinetic analysis of reaction catalyzed by the phage T7 RNA polymerase].

PMID- 9566256
TI  - [Chromatin organization in the tumor necrosis factor/lymphotoxin gene locus:
      correlation with tissue-specific expression].

PMID- 9566257
TI  - [Computer analysis of DNA sequences].

PMID- 9566258
TI  - [Stability of DNA complexes with peptide-nucleic acid].

PMID- 9566259
TI  - [Circular permutation of Thermus thermophilus ribosomal protein S6 to artificial
      protein albebetin topology].

PMID- 9566260
TI  - [Release of hydrophobic ligand from retinol-binding protein under conditions
      mimicked the membrane field].

PMID- 9566261
TI  - [Cooperative interactions in tandems of oligonucleotides and their derivatives on
      complementary template].

PMID- 9566262
TI  - [Mechanism of differentiating action of L-glutamic acid on HL-60 cells].

PMID- 9566263
TI  - [One of the kinesin light chains is selectively associated with mitochondria].

PMID- 9566264
TI  - [Modified nucleoside 5'-triphosphates with enhanced stability to
      dephosphorylating enzymes].

PMID- 9566265
TI  - [Mobile elements and speciation].

PMID- 9566266
TI  - Positive and negative syndromes, and Borna disease virus infection in
      schizophrenia.
AB  - The relationship between Borna disease virus (BDV) infection and positive and
      negative syndromes in schizophrenia was investigated. By nested RT-PCR and
      Western blotting, BDV-specific RNA and anti-BDV antibodies were examined in blood
      from 67 schizophrenic patients (DSM-III-R) in Japan, and the psychometric
      properties of the Positive and Negative Syndrome Scale (PANSS) were analyzed.
      There were significant (p < 0.05) differences in the composite index denoting the
      positive minus negative difference indicating a dominant contribution by negative
      items, and the proportion of negative type (positive minus negative value below
      zero) patients, between patients positive and negative for anti-BDV p24
      antibodies. It is possible that BDV infection with induction of BDV p24
      antibodies may be associated with negative syndromes in schizophrenic patients.

PMID- 9566267
TI  - Nitric oxide, free radicals and polyamines may have a role in the membrane
      pathology of schizophrenia.
AB  - Studies on skin fibroblasts in culture derived from schizophrenic and control
      subjects showed that polyamines are increased, nitrate levels are reduced and
      thiobarbituric acid reacting substances did not alter in cultured cells from
      schizophrenic patients compared to control subjects. Results seem to indicate
      some alteration in membrane functions in schizophrenia, which is susceptible to
      neuroleptic treatment. Significantly increased levels of polyamines in drug
      treated schizophrenic cells indicates a possible role of polyamines in the
      activation of proposed hypofunctional NMDA subtype of glutamate receptor systems
      in schizophrenia.

PMID- 9566268
TI  - Anxiety disorders and obsessive compulsive disorder.

PMID- 9566269
TI  - Drug treatment for bulimia nervosa.

PMID- 9566270
TI  - Depression, cardiac death, and the central nervous system.

PMID- 9566271
TI  - Clinical characteristics and management of unipolar depressive disorders comorbid
      with neurological disorders.

PMID- 9566272
TI  - Thyroid parameters during therapy with zotepine in delusional depression.
      Preliminary results.
AB  - There are only few data on the effects of atpyical neuroleptics on thyroid
      function. In an open pilot study of 12 inpatients with delusional depression,
      thyroid hormone levels and TRH-TSH test were determined during neuroleptic
      treatment with zotepine. No significant changes in triiodothyronine (T3),
      thyroxine (T4) and delta-TSH levels were found in this observation period (28
      days).

PMID- 9566273
TI  - Obsessive-compulsive symptom exacerbation following cortisone treatment.
AB  - We here report a case of obsessive-compulsive symptom exacerbation during
      cortisone therapy in an adult patient without organic brain disorder. Possible
      clinical and pathophysiological considerations are discussed.

PMID- 9566274
TI  - Interferon alpha-induced depression in chronic hepatitis C patients: comparison
      between different types of interferon alpha.
AB  - IFN alpha treatment is able to produce dose-related side effects, such as
      depression, in the central nervous system. We assessed the effects on depression
      of four different types of IFN alpha (recombinant IFN alpha 2a, recombinant IFN
      alpha 2b, lymphoblastoid IFN alpha, leukocyte IFN alpha), administered at the
      same doses in four homogeneous groups of chronic hepatitis C patients (96
      patients; 24 patients for each group). A group of 18 untreated hepatitis C
      patients was considered as a control group. Depression was measured using Zung's
      self-rating depression scale (SDS scale) before starting IFN alpha therapy and at
      the 1st, 3rd and 6th month of treatment. In all patients evaluated, mean SDS
      values increased from mild to moderate depression, but never attained severe
      depression (SDS > 70). More elevated SDS values were observed in the 1st month of
      treatment, with a progressive decrease during the end points above-mentioned. The
      recombinant IFN alpha 2a and lymphoblastoid IFN alpha arms presented higher SDS
      mean scores compared to the recombinant IFN alpha 2b and leukocyte IFN alpha arm.
      Only in the leukocyte IFN alpha arm SDS values returned to basal values at the 6
      month end point. Leukocyte IFN alpha seemed to present a more elevated
      tolerability than other IFN alpha types available for clinical practice. A very
      careful selection of hepatitis C patients is required before starting IFN alpha
      therapy.

PMID- 9566275
TI  - Scopolamine-induced impairment of delayed recognition of abstract visual shapes.
AB  - Since the limbic system, whose involvement in cognitive processes is well
      documented, constitutes a major central cholinergic area, the effect of
      cholinergic drugs on cognitive tasks has been studied extensively. In the present
      study, we used a long-term visual recognition task to evaluate the persistence of
      the scopolamine-induced anterograde amnesia beyond drug clearance intervals.
      Following memorization of a list of abstract shapes, subjects were evaluated on
      recognition performance immediately after encoding, and after a 3-day interval.
      Administration of scopolamine (0.4-0.8 mg) 70 min prior to encoding induced a
      significant (8-16%) deficit in delayed recognition performance. In contrast, a
      scopolamine challenge on delayed recognition following a drug-free encoding did
      not influence memory performance. In contrast, even at peak levels, scopolamine
      did not alter immediate recognition, detection or visual discriminative
      performances. Hence, the presence of scopolamine during the encoding of the
      shapes induced a significant long-term memory deficit that persisted after
      scopolamine clearance. Therefore, this paradigm is useful for imaging regional
      brain activation during impaired recognition without the confounding direct
      effects of scopolamine on cerebral blood flow or metabolism, two physiological
      variables underlying the indirect measurement of brain activation.

PMID- 9566276
TI  - The effects of tetrahydrocannabinol on the recognition of emotionally charged
      words: an analysis using event-related brain potentials.
AB  - The effects of synthetic tetrahydrocannabinol (THC) on event-related brain
      potentials (ERPs) were assessed in 19 healthy male volunteers while they
      performed a visual continuous word recognition task. The study used a double
      blind cross-over design. Specifically, word lists were manipulated to contain an
      equal number of emotionally neutral, negative, and positive words. Most words
      were repeated after several intervening items with the subject's task to classify
      each word as old (previously seen) or new. Behaviorally, a decrease in
      recognition rate was observed under THC but no influence of the emotional charge
      of a word on recognition rate was seen. The ERPs showed a typical difference
      between old and new words taking the form of an enhanced positivity for old words
      beginning 250 ms poststimulus. The effects of THC were confined to the positive
      words, for which an enhancement of the positivity to the old words was seen. This
      effect was interpreted in terms of a congruity of the drug-induced mood state and
      the material to be recognized. The dissociation between ERPs and behavioral
      indices suggested that the former primarily reflect implicit memory processes.

PMID- 9566277
TI  - Quantitative EEG effects of nicotine replacement by cigarette smoking.
AB  - The effects of cigarette smoking on the central nervous system can be assessed
      directly using the electroencephalogram (EEG). Nicotine withdrawal and subsequent
      replacement have been studied, but have produced conflicting effects on brain
      electrical activity. We studied the effect of smoking 2 cigarettes at subjects'
      own pace in 20 subjects. EEG was recorded using the EEGSYS program in the eyes
      closed awake state using a bipolar montage. Delta power decreased in central
      posterior head regions. Theta power and power in the lower half of the alpha band
      decreased. Beta power and power in the upper half of the alpha band increased
      significantly over frontotemporal head regions. Examination of spectra underlying
      the usual frequency bands revealed that many effects of smoking on EEG power
      probably resulted from a shift of the overall power spectrum toward higher
      frequencies, rather than resulting from alterations in activity in specific
      frequency bands.

PMID- 9566278
TI  - Alpha-smooth muscle actin distribution in the pulmonary vasculature comparing
      hypoplastic and normal fetal lungs.
AB  - We investigated the intra-acinar pulmonary vascular muscularization in the
      developing human fetal lung between the 17th and 24th gestational weeks, that is,
      during the canalicular phase of lung development. Fifteen hypoplastic and 25
      normal developed lungs were included in this study using monoclonal alpha-smooth
      muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image
      analysis was performed for morphometrical measurements and statistical
      evaluation. Alpha-sm-actin-immunoreactive intra-acinar vessels down to a luminal
      diameter of less than 10 microns were detected in hypoplastic as well as in
      normally developed lungs. Crucial differences presented as follows: significantly
      higher density of intra-acinar vessels, especially due to alpha-sm-actin-negative
      vessels less than 30 microns in luminal diameter, in the control group;
      significantly higher alpha-sm-actin immunore-activity per section unit as well as
      per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin
      positive cells of the intra-acinar vessel wall in the developing human lung were
      demonstrated to be smooth muscle cells, their immediate precursors, and
      pericytes. We conclude that the increased alpha-sm-actin immunoreactivity
      represents muscularization of the vessel wall in functional terms and may be
      regarded as one structural cause among others for the establishment of persistent
      fetal circulation in hypoplastic lungs.

PMID- 9566279
TI  - Detection of parvovirus B19 infection in first and second trimester fetal loss.
AB  - Fetal and placental tissues and maternal sera from a series of 273 cases of first
      and second trimester fetal loss were collected to detect the frequency of
      parvovirus B19 infection. In addition, fetal tissues were studied for the
      presence of congenital anomalies. Serology of maternal sera, histology of fetal
      tissues and placenta, polymerase chain reaction (PCR), in situ hybridization
      (ISH), and immunohistochemistry (IHC) were used for the detection of parvovirus
      B19 infection. Sera were tested for B19-specific immunoglobulin M (IgM) and/or
      IgG using an enzyme-linked immunosorbent assay technique. Based on serology, 149
      cases not related to B19 infection were excluded from further analysis. Two of
      the remaining 124 cases (0.7% of all 273 cases) had parvovirus B19-specific IgM
      and IgG at the time of abortion, indicating a recent maternal parvovirus B19
      infection. In our histological examination, 10 cases contained nuclear
      vacuolization in fetal erythroid progenitor cells, either in fetal tissues (n =
      2) or in placental tissue (n = 8). However, this vacuolization was considered a
      fixation artifact and not identical to parvovirus B19-specific nuclear inclusions
      described in previous reports. Only 1 of these 10 cases had parvovirus B19 DNA
      detectable in placental tissue by PCR analysis. Neither in this case nor in any
      of the other cases tested was parvovirus B19 DNA or protein detectable by ISH or
      IHC, respectively. In none of 41 cases in which fetal tissues were available were
      congenital anomalies found. In conclusion, the frequency of maternal parvovirus
      B19 infection in this series of fetal losses is low (0.8%). This low frequency
      does not allow any conclusions with regard to the occurrence of congenital
      anomalies resulting from parvovirus B19 infection and the usage of nuclear
      histology for the detection of fetal parvovirus B19 infection is considered a
      nonspecific parameter that requires confirmation by PCR.

PMID- 9566280
TI  - Use of fine needle aspiration for fibroblast culture.
AB  - Diagnosis in certain metabolic diseases or the establishment of long-term
      reservoirs of cytogenetic material requires tissue culture of fibroblasts
      obtained by skin snip or punch biopsy. Fine needle aspiration biopsy (FNAB) was
      investigated as an alternative method of fibroblast collection with advantages of
      minimal morbidity and the potential of better patient acceptance. After flank
      FNAB, culture, and incubation, confluent fibroblast growth was achieved within 19
      days. The number of cells produced was sufficient for potential cytogenetic or
      metabolic studies. Cultured fibroblasts obtained via FNAB proved to be a
      successful alternative to skin biopsy, with reduced trauma and better cosmetic
      results.

PMID- 9566281
TI  - Blood glucose determinations in newborns: four instruments compared.
AB  - Four portable analyzers, HemoCue B-Glucose (I), Accu-Check III (II), One-touch II
      (III), and Glucometer Elite (IV), with different measuring principles were tested
      for their suitability for measuring blood glucose in neonates. Precision of all
      instruments is satisfactory. In the analysis of capillary blood from newborns,
      two instruments show an excellent accuracy; however, the scatter of the results
      for instrument (II) is about 1.6 times greater than for instrument (I). The
      inaccuracy of instruments (III) and (IV) is not acceptable from a clinical point
      of view. All devices show an influence of hematocrit, the magnitude of which
      varies between 5% (I) and 12% (III) for every 10% change of hematocrit.
      Instruments II and IV show that temperature has a marked influence on the
      readings; the same is true for oxygen in instrument IV. In conclusion, only
      instrument (I) has met the requirements of accurate and precise blood glucose
      determinations in neonates.

PMID- 9566282
TI  - Cytomegaly of pancreatic D cells in triploidy.
AB  - Triploidy is a common chromosomal aberration seen in 1% of clinically recognized
      human pregnancies. Development beyond 10 weeks is unusual. Occasionally fetuses
      survive past 20 weeks; however, they usually present as a stillbirth with only a
      few managing some hours of independent life. The clinical features of these
      infants cover a wide spectrum, but a consistent feature is organ hypoplasia and
      hypotonia. We observed marked enlargement of somatostatin-producing cells (D
      cells) in the pancreata of triploid fetuses. Somatostatin-producing cells are
      widely distributed in normal mammals although concentrated in the pancreas and
      gastrointestinal tract, generally being antiproliferative and having an
      inhibitory effect on various functions. The control of fetal growth is not well
      understood. There is, however, some evidence that somatostatin does play a
      significant part and our consistent observation of cytomegaly of the pancreatic D
      cells in growth-retarded triploid fetuses provides more support for this
      contention.

PMID- 9566284
TI  - Atypical Pneumocystis carinii pneumonia in a child with hyper-IgM syndrome.
AB  - Children with hyper-immunoglobulin M (hyper-IgM) syndrome are at increased risk
      for Pneumocystis carinii pneumonia (PCP), an opportunistic infection often found
      in immunodeficient hosts. PCP can present with increasing hypoxia, fever, cough,
      and respiratory distress. We describe a child with hyper-IgM syndrome in whom
      bronchoalveolar washings were negative for PCP. However, there was an atypical
      lung response in which caseating granulomas predominated. The histopathology,
      resembling that found in tuberculosis, stresses the importance of a high index of
      clinical suspicion and histologic confirmation for early intervention and
      treatment. Immunocompromised children with rapidly progressive pulmonary disease
      may require lung biopsy and stains such as GMS to identify PCP.

PMID- 9566283
TI  - Alterations of the enteric nervous system in neonatal necrotizing enterocolitis
      revealed by whole-mount immunohistochemistry.
AB  - Pathology reports on neonatal necrotizing enterocolitis (NNEC) rarely consider
      its effects on the enteric nervous system (ENS). Thus, the aim of this study has
      been to perform a two-dimensional assessment of neuropathologic lesions within
      the three ganglionated plexuses of the intestinal wall by means of whole-mount
      immunohistochemistry. Resected segments of ileum and colon affected by acute NNEC
      were submitted to immunohistochemical procedures using antibodies against
      neuronal (protein gene product 9.5) and glial (protein S-100, glial fibrillary
      acidic protein) proteins. Examination of the myenteric plexus and external
      submucosal plexus revealed a noticeable reduction in glial cells concomitant with
      the gradual deterioration of nerve cells, both findings predominating in the
      antimesenteric intestinal circumference, where ischemic lesions tend to appear
      first. The most severe damage of nervous tissue was observed in the plexus
      submucosus internus dependent on the depth of mucosal injury. The destroyed
      ganglia appeared like "empty baskets" (residual tangles) and housed deteriorated
      nerve and glial cells. Taking the anatomy of the intestinal vascular blood supply
      into consideration, the characteristic topography of neuropathologic lesions
      gives further support to an ischemic event within the cascade of different
      pathogenetic factors culminating in NNEC. Moreover, the demonstrated alterations
      of the ENS and their potential adverse effects on intestinal motility and
      neuroimmunologic interactions may contribute to the complex pathogenesis of NNEC,
      which remains a field of further investigation.

PMID- 9566285
TI  - Child fatality associated with pathological features of histiocytic necrotizing
      lymphadenitis (Kikuchi-Fujimoto disease).
AB  - We report a case of histiocytic necrotizing lymphadenitis without granulocytic
      infiltration (Kikuchi-Fujimoto disease), diagnosed at necropsy in a 19-month-old
      child dying unexpectedly after a febrile illness. This is the youngest case with
      this disease that has been thus far reported. It is one of only two reported
      cases in which the patient died during the acute phase of the illness.
      Histological findings not unlike those seen in the lymph nodes were present at
      extranodal sites; this is the first case in which this feature has been
      described. In keeping with many other reported cases, it was not possible to
      identify an underlying etiology that might explain the morphologic changes.

PMID- 9566287
TI  - Renal medullary carcinoma: a potential sickle cell nephropathy of children and
      adolescents.
AB  - An extremely aggressive malignant epithelial neoplasm of the kidney has recently
      been described and named renal medullary carcinoma. The finding of this tumor is
      highly predictive of drepanocytes (sickle cells) in tissue sections and thus the
      presence of sickle hemoglobin, specifically sickle cell trait, in the patient. We
      present a case report of this rare tumor in a 10-year-old male. The tumor
      displayed a variable histologic architecture including gland-like areas with
      intra- and extracytoplasmic material resembling mucin with hematoxylin and eosin
      stain. This material was negative with periodic acid-Schiff and mucicarmine
      stains, stained only weakly with Alcian Blue, and was positive using antibodies
      against peanut agglutinin. Tumor cells stained positively with antibodies to
      epithelial membrane antigen, cytokeratin, vimentin, and Ulex europaeus lectin.
      The luminal face of tumor cells stained with peanut agglutinin. Stains using
      antibodies against carcinoembryonic antigen and alpha-fetoprotein were negative.
      Ultrastructurally, the tumor cells were characterized by short microvilli lining
      the luminal surface and lateral complex infoldings of adjacent plasma membranes.
      We discuss the relationship of this neoplasm to another renal pelvic neoplasm,
      collecting duct carcinoma, which may rarely occur in children. Renal medullary
      carcinoma should be included in the differential diagnosis of gross hematuria,
      which is most commonly benign self-limited hematuria, in young patients with
      sickle cell trait.

PMID- 9566286
TI  - Amebic osteomyelitis in a child with acquired immunodeficiency syndrome: a case
      report.
AB  - Disseminated Acanthamoeba infection has been described in immunocompromised or
      debilitated patients. The usual sites of involvement are skin, sinus, and brain.
      Sporadic reports of Acanthamoeba infection in patients infected with the human
      immunodeficiency virus are present in recent literature, predominantly in adults,
      and one case involving an 8-year-old child. We describe a case of amebic
      osteomyelitis, seen in a 6-year-old child with vertically acquired human
      immunodeficiency virus and a 6-month history of cutaneous Acanthamoeba infection.

PMID- 9566288
TI  - Cytogenetics of an atypical Spitz nevus metastatic to a single lymph node.
AB  - Clinicopathologic details of an atypical Spitz nevus are reported. A metastasis
      to a single ipsilateral lymph node is documented. Cytogenetic analysis of the
      metastatic lesion revealed a clonal chromosomal abnormality, add(6)(q12-13),
      previously noted in cases of malignant melanoma.

PMID- 9566289
TI  - [Tetrapyrroles: diversity, biosynthesis, biotechnology].
AB  - Various aspects of metabolism and biotechnology of tetrapyrroles are reviewed.
      Structures and properties of newly discovered tetrapyrrole pigments, biosynthesis
      of most important functional tetrapyrroles (hemes, chlorophylls, corrinoids,
      siroheme, and methanogenesis factor F430), and biotechnological methods of
      production of porphyrins and corrinoids are discussed. 5-Aminolevulinic acid is
      shown to be a promising anticancer preparation.

PMID- 9566290
TI  - [Biosensors for detecting organic compounds. II. Sensors for carbohydrates,
      aromatic, heterocyclic and other organic compounds].
AB  - The use of biosensors for detecting aromatic compounds (aniline, hydroquinone,
      phenol, and N,N-dimethyl-p-phenylenediamine), heterocyclic compounds (adenosine,
      AMP, ATP, bilirubin, hypoxanthine, guanine, inosine, inosine 5'-phosphate,
      xanthine, creatinine, uric acid, and NAD), carbohydrates (glucose, galactose,
      lactose, maltose, and sucrose), vitamins, antibiotics, steroids, mutagens, and
      organophosphorous pesticides is discussed. Basic metrological characteristics of
      these biosensors are reviewed.

PMID- 9566291
TI  - [Preparation and properties of pancreatin immobilized on carboxymethylcellulose].
AB  - A method for immobilizing pancreation on carboxymethylcellulose (CMC) is
      proposed. The optimum reaction conditions were determined: CMC, 1 x 10(-4) M; 1
      ethyl 3-(dimethylaminopropyl)-carbodiimide, 2 x 10(-4) M; incubation time, 18 h
      at 4 degrees C. They allow obtaining a conjugate of the enzyme with the polymer
      displaying 85% of the protease and 92% of the esterase activity. Both the native
      and immobilized enzymes were shown to contain thermolabile and thermostable
      fractions with different inactivation constants. Immobilization of the enzyme was
      found to increase its thermal stability by a factor of 1.5 to 3. Thermodynamic
      constants of blood protein hydrolysis by native and immobilized enzymes were
      determined.

PMID- 9566292
TI  - [Method of assessing the carbohydrate specificity of interaction of
      immunoglobulins with biotinylated lectins].
AB  - A method for analysis of mammalian immunoglobulins--an analogue of enzyme
      immunoassay--with biotin-conjugated vegetable lectins as specific reagents was
      proposed. The method enables the use of biotin-conjugated lectins for studies of
      immunoglobulin glycosylation.

PMID- 9566293
TI  - [Preparation of lymphotoxin and properties of it].
AB  - The process of isolation of highly purified human lymphotoxin was studied and
      optimized. A set of methods providing an increase in the content of the target
      product in the biomass (plasmid DNA amplification and selection of clones of
      transformed cells) was applied at the stage of cultivation. A two-step
      purification scheme (ion-exchange chromatography on DEAE-Biotone A1 and
      hydroxylapatite) was developed. A number of physical characteristics were
      studied.

PMID- 9566294
TI  - A review of the environmental fate, effects, and exposures of bisphenol A.
AB  - Bisphenol A (CAS 85-05-7) may be released into the environment through its use
      and handling, and permitted discharges. BPA is moderately soluble (120 to 300
      mg/L at pH 7), may adsorb to sediment (Koc 314 to 1524), has low volatility, and
      is not persistent based on its rapid biodegradation in acclimated wastewater
      treatment plants and receiving waters (half-lives 2.5 to 4 days). BPA is
      "slightly to moderately" toxic (algal EC50 of 1000 micrograms/L) and has low
      potential for bioaccumulation in aquatic organisms (BCFs 5 to 68). The chronic
      NOEC for Daphnia magna is > 3146 micrograms/L. Surface water concentrations are
      at least one to several orders of magnitude lower than chronic effects, with most
      levels nondetected.

PMID- 9566295
TI  - Atmospheric mercury deposition on Fanjing Mountain Nature Reserve, Guizhou,
      China.
AB  - Fanjing Mountain Nature Reserve (FMNR) is surrounded with several Hg emission
      sources within distances of 100-200 km. At the two sites studied, Tongren and
      Danzai, Hg emission and deposition fluxes, Hg concentration in the air, soil and
      other samples are all several hundred times higher than at other relatively clean
      areas. Hg accumulation in soil and moss at FMNR varies with the sampling heights.
      Total Hg deposition to this area has been estimated to be 115 micrograms m-2 y-1
      using moss bag technique. Dry deposition was determined to be about 5.2
      micrograms m-2 month-1 during March to June, corresponding to more than 50% of
      the total deposition.

PMID- 9566296
TI  - Comparative levels of organochlorine compounds in flounders from the northeast
      coast of Newfoundland and an offshore site.
AB  - Muscle tissue of yellowtail flounder, Pleuronectes ferruginea (n = 6) and winter
      flounder, Pseudopleuronectes americanus (n = 9) collected from Bonavista Bay,
      Conception Bay and an offshore location off northeastern Newfoundland, Canada,
      were analyzed for PCBs and other organochlorine compounds to determine if there
      are geographical variations in the concentrations and patterns of these
      persistent contaminants. The concentrations of total PCB congeners on a wet
      weight basis were relatively homogeneous at low ng/g levels. DDE, HCH compounds,
      and components of technical chlordane were the dominant organochlorine
      contaminants. Lipid normalized data indicate that PCB concentrations were higher
      in both species collected in the moderately urbanized region of Conception Bay.
      Principal Component Analysis (PCA) of PCB congener patterns indicated that
      flounder collected in Conception Bay had greater proportions of highly
      chlorinated PCB congeners, which may indicate point-source contamination in this
      region. Concentrations and patterns of other organochlorine compounds were
      relatively consistent across all sampling locations.

PMID- 9566298
TI  - An indicator of pesticide environmental impact based on a fuzzy expert system.
AB  - Pesticide use options available to farmers differ strongly with respect to the
      risks they pose to the environment. This paper proposes a fuzzy expert system to
      calculate an indicator "Ipest" which reflects an expert perception of the
      potential environmental impact of the application of a pesticide in a field crop.
      We defined four modules, one reflecting the presence (rate of application) of the
      pesticide, the other three reflecting the risk for three major environmental
      compartments (groundwater, surface water, air). The input variables for these
      modules are pesticide properties, site-specific conditions and characteristics of
      the pesticide application. For each input variable two functions describing
      membership to the fuzzy subsets Favourable (F) and Unfavourable (U) have been
      defined. These functions are based on criteria drawn from the literature or on
      the authors' expert judgment. The expert system calculates the value of modules
      according to the degree of membership of the input variables to the fuzzy subsets
      F and U and according to sets of decision rules. The four modules can be
      considered individually or can be aggregated (again according to membership to
      fuzzy subsets F and U and a set of decision rules) into the indicator Ipest. The
      system is flexible and can be turned to expert perception, it can be used as a
      decision aid tool to rank or choose between alternative pesticide application
      options with respect to their potential environmental impact. Results of a
      sensitivity analysis and module and Ipest scores for some pesticide application
      cases are presented. An agro-ecological indicator IPEST, based on the expert
      system, is proposed as a tool to assess the environmental impact of all pesticide
      applications related to a crop within a year. The practical implementation of the
      expert system and its validation are discussed.

PMID- 9566297
TI  - The use of 13C-labelled polycyclic aromatic hydrocarbons for the analysis of
      their transformation in soil.
AB  - The formation of non-extractable residues during biodegradation and humification
      processes in soils and sediments represents a major sink for organic
      contaminants. The mode of incorporation of polycyclic aromatic hydrocarbons (PAH)
      and their metabolites into macromolecular organic matter during microbial
      degradation was studied applying 13C-labelled compounds. Mineralisation rates
      were determined by measuring the 13CO2 production. An incorporation of 13C-PAH
      fragments into humic material could be traced by isotopic analysis of the bulk
      organic matter. Furthermore, selective chemical degradation reactions were
      performed to analyse the precise chemical structure of covalently bound 13C
      labelled PAH fragments in soil humic substances. Structural assignments by GC-MS
      combined with isotope measurements on the bulk organic carbon and at the
      molecular level (Isotope Ratio Monitoring-GC-MS) provided useful information on
      the fate of xenobiotics within the soil.

PMID- 9566299
TI  - Formation of 3-amino-2,6,8-trimethyl-10-phenyldeca-4E,6E-dienoic acid from
      microcystin LR by the treatment with various proteases, and its detection in
      mouce liver.
AB  - Microcystin LR metabolism in mammals was examined. The degradation of microcystin
      LR by the enzymes, pepsin, trypsin and chymotrypsin, from porcine or human
      gastrointestinal tract was examined. Microcystin LR was digested by these
      proteases, but 3-amino-2, 6, 8-trimethyl-10-phenyldeca-4E, 6E-dienoic acid
      (DmADDA) was not formed from microcystin LR treated with pepsin and chymotrypsin.
      The formation of DmADDA was detected from microcystin LR treated with trypsin.
      Furthermore, DmADDA was detected from the male ddY mice liver orally administered
      microcystin LR.

PMID- 9566300
TI  - A simplified modeling approach using microbial growth kinetics for predicting
      exposure concentrations of organic chemicals in treated wastewater effluents.
AB  - Various mathematical relationships have been used to assess exposure
      concentrations of organic chemicals when emissions occur via wastewater
      treatment. These relationships range from a simple removal factor calculation to
      more sophisticated approaches using kinetic based mathematical models. While
      these existing approaches have been used by decision makers to screen new
      chemicals for exposure assessments, they all have limitations in the predictive
      capabilities. Thus, a simplified modeling approach grounded in sound scientific
      fundamentals that utilizes relatively easy to obtain input parameters is needed.
      In this paper a simplified modeling approach that utilizes microbial growth
      kinetics was developed for predicting effluent concentrations in secondary
      biological wastewater treatment systems. Receiving water predicted exposure
      concentrations (PEC) are assessed by using a dilution factor. One advantage of
      this approach is that it allows for wastewater treatment plant effluent
      concentrations, and therefore receiving water exposure levels, to be predicted
      with a minimum amount of experimental data. It also provides quantitative data
      that can be used to assess the relative biodegradability of different chemicals
      for use in regulatory and risk assessment activities.

PMID- 9566301
TI  - Site-specific lead distribution in scales of lead-administered carp (Cyprinus
      carpio) by non-destructive SR-XRF analysis.
AB  - By utilizing non-destructive synchrotron radiation-excited X-ray fluorescence (SR
      XRF), we observed the distribution of lead (Pb) in both ontogenic and
      regenerating scales of lead-administrated carp, Cyprinus carpio. The fish in the
      Pb-administered group were fed pellets containing 1 mg/g of Pb at a rate of 1.5%
      body weight per day for 30 days. In the ontogenic scales, Pb was highly
      accumulated near the basal edge of the scale and the accumulated amount decreased
      toward the focus of the scale. On the other hand, in the regenerating scales,
      high accumulation was observed near the basal edge and the accumulated amount
      remained high toward the focus. The present results of Pb accumulation correspond
      well with the region which is calcifying in the ontogenic and regenerating
      scales, and indicate that the distributions of Pb show when and how long Pb was
      administered.

PMID- 9566302
TI  - Effect of selected environmental factors on degradation and mineralization of
      biaryl compounds by the bacterium Ralstonia pickettii in soil and compost.
AB  - By varying selected environmental factors, the degradation and mineralization of
      biaryl compounds by the bacterium Ralstonia pickettii in soil and compost were
      investigated. An optimized soil moisture and enhanced bioavailability by using
      the nonionic surfactant Tween 80 were of great importance for the degradation
      rates of biaryl compounds like biphenyl and 4-chlorobiphenyl by cells of
      Ralstonia picketti SBUG 290 inoculated into soil. Additionally, degradation of
      these compounds by the investigated strain in soil was strongly dependent upon
      the medium of precultivation. Also the influence of temperature and soil pH-value
      was tested. In contrast to the used soil, the autochthonous flora of the compost
      seemed to have a higher physiological activity. All investigated compounds
      (biphenyl, 4-chlorobiphenyl and dibenzofuran) were degraded quickly in compost.
      Inoculation with the investigated bacterium did not enhance the degradation rates
      significantly.

PMID- 9566303
TI  - Toxicity and anaerobic biodegradability of pyridine and its derivatives under
      sulfidogenic conditions.
AB  - Attempts were made to correlate the chemical structure of pyridine and 15
      pyridine derivatives with both their biodegradability by estuarine sediment
      microorganisms under anaerobic conditions and also with their toxicity to the
      marine bacterium Vibrio fischeri Beijerinck 1889 by using the Microtox bacterial
      assay. Among monosubstituted pyridines, comparisons of different substituents at
      positions C-2, C-3, or C-4 atom of the pyridine ring showed that isomers of
      carboxylpyridine (COOHPYR), hydroxypyridine (OHPYR), and cyanopyridine (CNPYR)
      were more susceptible to biotransformation than isomers of chloropyridine (ClPYR)
      and methylpyridine (CH3PYR) in anoxic estuarine sediment slurries under
      sulfidogenic conditions. Isomers with the functional group at the C-2 or C-3 atom
      of the pyridine ring were biotransformed faster than those with the same
      functional group at C-4. The only exception was 4-ClPYR, which was biotransformed
      within 130 days, while 2- and 3-ClPYR continued to persist in the anoxic sediment
      slurries. Median effect concentrations (EC50) of pyridine and pyridine
      derivatives were in the range of 0.027 to 49.1 mmol/L. Pyridine derivatives with 
      CN and -OH functional groups tended to be less toxic, while pyridine derivatives
      with -CH3, -Cl, and -COOH functional groups tended to be more toxic. Isomers with
      the substituent at C-2 were less toxic than the C-3 or C-4 isomers. There was no
      clear correlation between the pseudo-first-order rate constants for the microbial
      transformation of pyridine and its derivatives and their toxicity to the marine
      bacterium.

PMID- 9566304
TI  - Differential effects of heavy metals on the binding of Xenopus upstream binding
      factor(xUBF) to DNA.
AB  - Xenopus upstream binding factor (xUBF) is a transcription factor for RNA
      polymerase I which contains multiple DNA-binding motifs. Among these DNA-binding
      motifs, HMG box I is essential for promoting RNA polymerase I-dependent rRNA gene
      transcription. Gel shift assay indicated that the binding of recombinant HMG box
      I to a 136-bp linear DNA probe was significantly inhibited by Cd2+ at 1 microM.
      The formation of larger protein-DNA complexes was particularly sensitive to Cd2+.
      The interaction between HMG box I and DNA was completely inhibited by 10 microM
      of Cd2+, yet this interaction was not inhibited by the same concentration of
      Ca2+. Hg2+ at 0.1 microM began to cause abnormal band shifting, and protein-DNA
      bands disappeared to the wells of a polyacrylamide gel in the presence of 10
      microM of Hg2+, reflecting that a drastic change in the conformation of HMG box I
      DNA had occurred. The binding of HMG box I to DNA was slightly disturbed by As3+
      at 1 microM and was significantly affected at 10 microM. Our results suggest that
      inhibition of the normal binding of UBF to its target DNA may be one of the
      mechanisms of heavy metal-induced inhibition of RNA synthesis.

PMID- 9566305
TI  - The use of the mitochondrial transmembrane electric potential as an effective
      biosensor in ecotoxicological research.
AB  - In this work, the mitochondrial transmembrane electric potential (delta psi) of
      isolated mitochondria was used to evaluate the toxicity of some chemicals
      (endosulfan, 3,4-dichloroaniline, parathion, tributyltin and cadmium) and
      wastewater. Mitochondria were isolated from rat liver, and the delta psi measured
      in a suitable assay medium, using a sensitive tetraphenylphosphonium (TPP+)
      electrode. The test substance was pre-incubated in a rotenone-containing medium
      during 3 min with 1.0 mg of mitochondrial protein. Mitochondria were energised
      with succinate and after the establishment of a constant maximal potential ADP
      was added to induce the phosphorylative cycle. Chosen endpoints were the membrane
      potential from mitochondria oxidising succinate and the depolarisation induced by
      ADP. After the appropriate transformations the EC50 (effective concentration) was
      calculated for each toxicant. Even very low concentrations of a toxicant were
      able to affect the delta psi, thus showing its suitability as a biosensor in
      ecotoxicology and results were reproducible between tests. The utilisation of
      delta psi in screening tests of pure substances and wastewater seems to be very
      effective and can be carried out routinely.

PMID- 9566306
TI  - Transcription factor Stat5 is an early marker of differentiation of murine
      embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent descendants of the inner cell mass of
      blastocysts capable of differentiating into progenitor cells of most if not all
      tissues. The pluripotency of ES cells is maintained by leukemia inhibitory factor
      (LIF), a member of the family of interleukin-6-type cytokines. These cytokines
      activate Janus tyrosine kinases and signal transducer and activator of
      transcription factors (Stat) via the signalling receptor component gp130.
      Pluripotent ES1 cells proliferating in the presence of LIF were known from
      previous studies to contain Stat3 and Stat1 capable of transcriptional
      activation. Here we report that the level of tyrosine-phosphorylated Stat3
      decreases rapidly during differentiation induced by treatment of ES1 cells either
      with retinoic acid (RA) or by withdrawal of LIF. In line with this finding, the
      DNA-binding activity of Stat3 decreased during differentiation. In contrast,
      Stat5 was absent from pluripotent proliferating ES cells, but appeared early
      after induction of differentiation. The positive correlation between induction of
      differentiation and expression of Stat5 mRNA was confirmed for three independent
      ES cell lines. Stat5 transcripts were detectable in ES1 cells as early as 12 h
      after treatment with RA and 36 h after withdrawal of LIF. Stat5 protein was
      detectable 2 days after the onset of differentiation. These results establish
      Stat5 as a novel marker of very early stages of differentiation of ES cells.

PMID- 9566307
TI  - Estrogen receptor-negative epithelial cells in mouse mammary gland development
      and growth.
AB  - The mouse mammary gland undergoes rapid proliferation during puberty, then
      cyclical proliferation and involution during adulthood within a 5-day estrous
      cycle. Although proliferation of mammary epithelial cells is directed by elevated
      serum levels of estrogen acting via the estrogen receptor (ER), the ER status of
      the proliferating cells remains unknown. We examined the ER expression of
      proliferating epithelial cell types during pubertal development and normal adult
      growth using simultaneous immunohistochemistry for ER and tritiated thymidine (3H
      Tdr) autoradiography. These studies demonstrate that during pubertal growth (4-6
      weeks) ER-negative cells comprise more than 50% of the epithelial cell
      populations in the terminal end buds (TEBs) and ducts. Furthermore, the majority
      of proliferating cells in both TEBs and ducts are ER-negative. These findings
      indicate that proliferation of cells within both the TEBs and the mammary ducts
      contribute to pubertal growth of the mammary gland and that the greater
      proportion of dividing cells are ER-negative. Similar patterns of cell growth
      were observed in the normal estrous cycle when the majority of dividing cells
      were ER-negative during both pro-estrous and estrous. Intensive labelling of
      cells with 3H-Tdr was used to identify long-lived mammary epithelial cells which
      retained 3H-Tdr 2 weeks following labelling (i.e., following 3 estrous cycles).
      Of the small number of mammary epithelial cells retaining 3H-Tdr label, most were
      ER-positive luminal cells and only a few were ER-negative basal cells. This study
      indicates that pubertal growth of the mammary gland comprises division of ER
      negative cap cells and of both ER-negative and ER-positive cells in the body of
      the TEBs and elongating mammary ducts. Similarly, estrogen-driven proliferation
      of ER-negative and ER-positive luminal cells and ER-negative basal cells
      maintains the differentiated mammary gland in the adult mouse.

PMID- 9566308
TI  - Enlargement of the ampullary gland and seminal vesicle, but not the prostate in
      int-2/Fgf-3 transgenic mice.
AB  - Expression of the int2/Fgf-3 gene occurs during normal embryonic development and
      is associated with mammary cancer in mice. Overexpression of this gene under the
      control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) in males
      was reported to result in prostatic enlargement. In this report male Fgf-3
      overexpressing mice were shown to have enlarged ampullary glands, seminal
      vesicles, and ductus deferens; there was extensive epithelial hyperplasia in the
      ampullary glands and seminal vesicles. The prostates of these animals were of
      normal size and histology. The transgene was expressed in all of the enlarged
      organs, which are derived exclusively from the Wolffian duct. Male secondary sex
      organs derived from the urogenital sinus, e.g., the ventral prostate, coagulating
      gland, and bulbourethral glands, were normal and did not express the MMTV-LTR
      driven Fgf-3 transgene. A dorsolateral prostate was also morphologically normal
      but did express the transgene. This study underscores the importance of careful
      organ identification in transgenic models in which gross organ enlargement or
      distortion occurs. It also highlights the heterogeneity of the response to Fgf-3
      among the secondary sex organs and even within the prostate itself.

PMID- 9566309
TI  - Induction of precocious pepsinogen synthesis by glucocorticoids in fetal rat
      gastric epithelium in organ culture: importance of mesenchyme for epithelial
      differentiation.
AB  - Glucocorticoids significantly affect both proliferation and differentiation of
      gastric epithelial cells in vivo. Here we examined the mechanism of action of
      glucocorticoids on the cells in vitro, with special reference to the epithelial
      mesenchymal interaction. When 16.5-day fetal rat gastric explants were maintained
      in organ culture, the epithelial cells began to invaginate into mesenchyme on
      days 3 to 4, and formed glandular structures on days 5 to 6 in culture.
      Immunohistochemical analysis with specific antibodies revealed that pepsinogen
      synthesizing cells first appeared on day 2, and they increased in number with
      epithelial morphogenesis to about 20%-30% of total epithelial cells on days 4 to
      6, and that these cells were localized at the base of glandular structures in
      control media. When the explants were treated with hydrocortisone (1
      microgram/ml), epithelial morphogenesis was mostly suppressed, but epithelial
      cytodifferentiation was significantly stimulated, indicating that epithelial
      morphogenesis is not necessary for their cytodifferentiation. In glucocorticoid
      treated explants, pepsinogen-synthesizing cells first appeared on day 1, and more
      than 90% of the cells were positively stained with the antibodies from days 3 to
      5 in culture. Biochemical analysis showed that much higher acid protease activity
      could be detected in glucocorticoid-treated explants than in controls from days 2
      to 6 in culture, and analysis by zymography indicated that the synthesis of
      pepsinogen 1 but not cathepsin E was stimulated by the hormone. Northern blotting
      analysis showed that the level of pepsinogen 1 mRNA was greatly increased by
      glucocorticoids. Examination of the effect of the hormone on the epithelial
      proliferation showed that hydrocortisone (1 microgram/ml) significantly inhibited
      the epithelial growth from days 1 to 3 in culture. To investigate the role of
      epithelial-mesenchymal interaction in the glucocorticoid-induced differentiation
      of the gastric epithelial cells, effects of the hormone on the proliferation and
      differentiation of the cells in the absence of mesenchyme were examined, using a
      recently established primary culture system. The epithelial cells synthesized
      cathepsin E but not pepsinogen in cell culture, irrespective of glucocorticoid
      treatment, and the level of acid protease activity was not affected by the
      hormone, indicating that mesenchyme is necessary for the hormone to induce
      pepsinogen gene expression in the epithelial cells. In the cell culture system,
      glucocorticoids did not inhibit but significantly stimulated epithelial
      proliferation. This suggests that the hormone indirectly inhibited epithelial
      proliferation in organ culture, probably via mesenchyme. The mechanism of action
      of glucocorticoids on the epithelial-mesenchymal interaction in the fetal
      glandular stomach is discussed.

PMID- 9566310
TI  - Acquisition of cell adhesion and induction of focal adhesion kinase of human
      colon cancer Colo 201 cells by retinoic acid-induced differentiation.
AB  - The human colon adenocarcinoma cell lines Colo 201 and Colo 205 lose adhevise
      capacity to the extracellular matrix (ECM) and take on a round and floating cell
      shape. Treatment of these cells with all-trans-retinoic acid (RA) results in
      inhibition of growth and in a marked increase in the production of
      carcinoembryonic antigen, thereby indicating that the cells undergo
      differentiation. This RA-induced differentiation was accompanied by a large
      increase in the degree of cell adhesion with localization of E-cadherin molecules
      at cell-cell contact sites. We examined several adhesion molecules involved in
      cell-cell and cell-ECM interaction by immunoblotting, but no change in E
      cadherin, intercellular adhesion molecule-1, or CD44 was observed in RA-treated
      Colo 201 cells. Although the adhesion of Colo 201 cells to ECM depends on the Arg
      Gly-Asp sequence, levels of integrins, alpha 2, alpha 3, alpha 5, alpha V, and
      beta 1 in differentiated adherent cells were similar to those in untreated cells.
      In contrast to equivalent amounts of cell surface adhesion molecules before and
      after differentiation, intracellular focal adhesion kinase (FAK) was markedly
      induced during RA treatment, and the increase in FAK resulted in elevation of
      tyrosine-phosphorylated FAK. These findings suggest a role for FAK in activation
      of cell adhesion of RA-induced differentiation of these colon cancer cells. This
      may serve as an appropriate model to examine the mode of activation of the
      adhesive capacity of cancer cells.

PMID- 9566311
TI  - A NOESY-HSQC simulation program, SPIRIT.
AB  - A program SPIRIT (Simulation Program considering Incomplete Recovery of z
      magnetization and INEPT Transfer efficiency) has been developed to simulate three
      dimensional NOESY-HSQC spectra. This program takes into account (1) different
      transfer efficiency during INEPT and reverse INEPT durations due to differential
      relaxation rates and 1J coupling constants; (2) the different effect of the
      sensitivity-enhancement scheme on CH, CH2 and CH3 systems; and (3) incomplete
      recovery of longitudinal magnetization between scans. The simulation program
      incorporates anisotropic tumbling mode for symmetric tops, and allows for
      differential external relaxation rates for protons. Some well-defined internal
      motions, such as the fast rotation of methyl groups, are taken into account. The
      simulation program also allows for input of multiple conformations and their
      relative populations to calculate the average relaxation matrix to account for
      slow internal motions. With the SPIRIT program, the sensitivity-enhanced NOESY
      HSQC experiment can be used directly in the evaluation of the accuracy of
      structures, which can potentially be improved by direct refinement against the
      primary data.

PMID- 9566312
TI  - Chemical shift homology in proteins.
AB  - The degree of chemical shift similarity for homologous proteins has been
      determined from a chemical shift database of over 50 proteins representing a
      variety of families and folds, and spanning a wide range of sequence homologies.
      After sequence alignment, the similarity of the secondary chemical shifts of C
      alpha protons was examined as a function of amino acid sequence identity for 37
      pairs of structurally homologous proteins. A correlation between sequence
      identity and secondary chemical shift rmsd was observed. Important insights are
      provided by examining the sequence identity of homologous proteins versus
      percentage of secondary chemical shifts that fall within 0.1 and 0.3 ppm
      thresholds. These results begin to establish practical guidelines for the extent
      of chemical shift similarity to expect among structurally homologous proteins.

PMID- 9566313
TI  - Determination of the NMR structure of the complex between U1A protein and its RNA
      polyadenylation inhibition element.
AB  - RNA-protein recognition is critical to post-transcriptional regulation of gene
      expression, yet poorly understood at the molecular level. The relatively slow
      progress in understanding this important area of molecular biology is due to
      difficulties in obtaining good-quality crystals and derivatives, and in preparing
      samples suitable for NMR investigation. The determination of the structure of the
      complex between the human U1A protein and its polyadenylation inhibition element
      is described here. In this paper, we describe the sample preparation, spectral
      assignments, construction of the NOE-based distance constraints and methodology
      for calculating the structure of the complex. The structure was determined to an
      overall precision of 2.03 A (for all ordered regions), and 1.08 A for the protein
      RNA interface. The patterns of hydrogen bonding and hydrophobic interactions at
      the interface were analysed statistically using the final ensemble of 31
      structures.

PMID- 9566314
TI  - Improved distance analysis in RNA using network-editing techniques for overcoming
      errors due to spin diffusion.
AB  - Multispin magnetization transfer, or spin diffusion, is a significant source of
      error in NOESY-derived distance measurements for the determination of nucleic
      acid solution structures. The BD-NOESY and CBD-NOESY experiments, which allow the
      measurement of interproton distances with greatly reduced contributions from spin
      diffusion, have been adapted to structural analysis in RNA oligonucleotides. The
      techniques are applied to a lead-dependent ribozyme (LZ2). We demonstrate the
      measurement of both aromatic proton-aromatic proton NOEs free of spin diffusion
      involving the intervening ribose moieties and aromatic proton-ribose proton NOEs
      free of the efficient cross-relaxation within the ribose ring. In LZ2, the
      accuracy and precision of the resulting distances are significantly improved. We
      also find that, by allowing the use of longer mixing times with greater
      sensitivity, the experimental attenuation of spin diffusion in RNA increases the
      distance range of interactions that can be analyzed. This effect permits
      measurement of important long-range distances in LZ2 that are not accessible with
      standard techniques. Thus, these techniques allow the simultaneous optimization
      of the number, accuracy, and precision of distance constraints used for RNA
      structure determinations.

PMID- 9566316
TI  - The functionally and physiologically plastic adult auditory system.
AB  - The potential for functional and underlying physiological change in the adult
      auditory system is examined through review and evaluation of several sets of
      literature including auditory deprivation and recovery, auditory learning after
      hearing aid fitting, auditory abilities of normal listeners exposed to masking
      noise, and neural plasticity in the sensory and motor systems of animals. This
      tutorial review is meant for the reader who may be interested in auditory
      learning and who would like to have a summary and evaluation of the various
      findings to date. The focus of the review is the effect that various findings of
      auditory learning may have on hearing aid fitting and selection.

PMID- 9566315
TI  - An efficient and cost-effective isotope labeling protocol for proteins expressed
      in Escherichia coli.
AB  - A cost-effective protocol for uniform 15N and/or 13C isotope labeling of
      bacterially expressed proteins is presented. Unlike most standard protocols,
      cells are initially grown in a medium containing nutrients at natural abundance
      and isotopically labeled nutrients are only supplied at the later stages of
      growth and during protein expression. This permits the accumulation of a large
      cell mass without the need to employ expensive isotopically labeled nutrients.
      The abrupt decrease in oxygen consumption that occurs upon complete exhaustion of
      essential nutrients is used to precisely time the switch between unlabeled and
      labeled nutrients. Application of the protocol is demonstrated for wild-type and
      a mutant of the N-terminal zinc-binding domain of HIV-1 integrase.

PMID- 9566317
TI  - Mechanisms of the cochlear nucleus octopus cell's onset response: synaptic
      effectiveness and threshold.
AB  - Octopus cells are one of the principal cell types in the mammalian posteroventral
      cochlear nucleus. These cells respond to the onset of a toneburst with a
      precisely timed spike followed by little, if any, sustained activity. While
      experimental studies have partially characterized the cell, the mechanisms of
      this onset response are not well understood. The present study involved a model
      based investigation that analyzed the responses of a compartmental model of the
      octopus cell in terms of synaptic effectiveness and dynamic spike threshold. The
      simulations demonstrate that properties of the onset response (first-spike
      latency, temporal precision of the first spike, and sustained firing rate) can be
      predicted from the values of these cell properties for a wide range of model
      configurations. These relationships were further analyzed through the development
      of mathematical expressions for synaptic effectiveness and dynamic spike
      threshold. This computational analysis resulted in a relatively simple
      explanation of the onset response, as well as predictions of the responses of
      octopus cells to nontonal, complex stimuli.

PMID- 9566318
TI  - The role of the chinchilla pinna and ear canal in electrophysiological measures
      of hearing thresholds.
AB  - Measurements of the acoustic transfer function (ATF) of the pinnae of 8
      chinchillas were compared with the auditory-evoked potential (AEP) thresholds of
      16 chinchillas measured in free field and with insert earphones. The ATF was
      measured in anesthetized chinchillas in a far-field condition in a semi-anechoic
      room using a logarithmic frequency sweep from 100 Hz to 20 kHz. Probe microphone
      measurements were collected with the probe opening at the tympanic membrane and
      in the same approximate position with the chinchilla removed from the sound
      field. For each animal's acoustic transfer function, the average of five in-the
      ear and three free-field measurements were determined. The ATF exhibited a 5-dB
      passive gain at about 1 kHz and a broad resonance between 2.5 and 6 kHz of about
      a 10-dB gain. AEP thresholds were obtained from monaural chronically implanted
      chinchillas at 0.5, 1, 2, 4, and 8 kHz using first free-field and then insert
      earphone stimuli. The free-field sound pressure was measured with a microphone in
      the approximate position of the chinchilla's head. The earphone sound pressures
      were measured with a probe microphone positioned near the tympanic membrane. The
      free-field AEP hearing thresholds exhibited +10-dB gain at 4 kHz compared to the
      insert earphone AEP thresholds. The agreement between the ATF and AEP derived
      transfer function suggested that the threshold differences at 4 kHz between the
      two testing configurations can be accounted for by the pinna and ear canal gain.

PMID- 9566319
TI  - Locus of generation for the 2f1-f2 vs 2f2-f1 distortion-product otoacoustic
      emissions in normal-hearing humans revealed by suppression tuning, onset
      latencies, and amplitude correlations.
AB  - The present study used distortion-product otoacoustic emission (DPOAE)
      suppression tuning curves (STCs), DPOAE onset latencies (OLs), and DPOAE
      amplitude correlations to investigate the locus of generation of the 2f1-f2 DPOAE
      versus the 2f2-f1 DPOAE in humans. The results of the tuning study revealed that,
      for the 2f1-f2 DPOAE, the tips of the STCs tuned consistently below the geometric
      mean (GM) frequency of the primary tones. In contrast, for the 2f2-f1 DPOAE, STCs
      tuned above the GM of the primaries, with 50% of the tip frequencies at, or
      above, the 2f2-f1 frequency place. When the average ratio of the 2f2-f1 to the
      2f1-f2 tip frequencies was computed, a factor of 1.44 provided an estimate of the
      frequency shift needed to align the two DPOAE generation sites. Other results
      showed that OLs for the 2f2-f1 DPOAE were uniformly shorter than those for the
      2f1-f2, with differences at the low frequencies amounting to as much as 6-7 ms.
      Further, for both DPOAEs, curves describing latency decreases as a function of
      increasing GM frequencies were best fit by power functions. Shifting the GM
      frequency producing the 2f2-f1 DPOAE by a factor of 1.6 caused the latency
      distributions for both DPOAEs to overlap thus resulting in a single function that
      described cochlear delay as a function of GM frequency. Finally, for each GM
      frequency in the DP-gram, sliding correlations from 108 normal ears were
      performed on both DPOAEs by holding the primaries producing the 2f1-f2 DPOAE
      constant, while all 2f2-f1 DPOAE amplitudes were successively correlated with the
      2f1-f2 amplitudes. This procedure demonstrated that, for a given GM frequency
      producing the 2f1-f2, the correlations between the two DPOAEs peaked when the
      primaries of the 2f2-f1 were at a GM frequency that positioned the 2f2-f1
      frequency place near the GM of the primaries that produced the 2f1-f2 DPOAE. As a
      whole, the above findings strongly suggest that the 2f2-f1 DPOAE in humans is
      generated basal to the primary-tone place on the basilar membrane.

PMID- 9566321
TI  - Responses of auditory nerve fibers to trains of clicks.
AB  - Responses of auditory nerve fibers to trains of clicks were recorded in ketamine
      anesthetized chinchillas. By varying the number of clicks and the interclick
      interval, this study examined whether "post-onset adaptation," described in
      psychoacoustic experiments on localization, occurred in auditory nerve fibers.
      The results showed that the number of action potentials recorded from a nerve
      fiber in response to a train of clicks was a power function of the number of
      clicks. For interclick intervals of 2 ms or greater the exponent of the power
      function was 0.5, and this exponent did not change over a 20-dB range of
      intensities. The timing of action potentials relative to the click stimuli was
      measured using synchronization coefficients. The coefficients increased with
      interclick interval, decreased with increasing intensity, and were greater for
      fibers with low rates of spontaneous activity than for high spontaneous fibers.
      Recovery functions showed that for interclick intervals of 2 ms or more, the
      responses to the second click were at least 70% of the response to the initial
      click. The recovery depended upon the number of clicks in the train. These
      findings indicate that auditory nerve fibers respond to high rates of stimulus
      presentation and do not display the adaptation observed in localization studies.

PMID- 9566320
TI  - Basilar-membrane responses to clicks at the base of the chinchilla cochlea.
AB  - Basilar-membrane responses to clicks were measured, using laser velocimetry, at a
      site of the chinchilla cochlea located about 3.5 mm from the oval window
      (characteristic frequency or CF: typically 8-10 kHz). They consisted of
      relatively undamped oscillations with instantaneous frequency that increased
      rapidly (time constant: 200 microseconds) from a few kHz to CF. Such frequency
      modulation was evident regardless of stimulus level and was also present post
      mortem. Responses grew linearly at low stimulus levels, but exhibited a
      compressive nonlinearity at higher levels. Velocity-intensity functions were
      almost linear near response onset but became nonlinear within 100 microseconds.
      Slopes could be as low as 0.1-0.2 dB/dB at later times. Hence, the response
      envelopes became increasingly skewed at higher stimulus levels, with their center
      of gravity shifting to earlier times. The phases of near-CF response components
      changed by nearly 180 degrees as a function of time. At high stimulus levels,
      this generated cancellation notches and phase jumps in the frequency spectra.
      With increases in click level, sharpness of tuning deteriorated and the spectral
      maximum shifted to lower frequencies. Response phases also changed as a function
      of increasing stimulus intensity, exhibiting relative lags and leads at
      frequencies somewhat lower and higher than CF, respectively. In most respects,
      the magnitude and phase frequency spectra of responses to clicks closely
      resembled those of responses to tones. Post-mortem responses were similar to in
      vivo responses to very intense clicks.

PMID- 9566322
TI  - Effects of wide band inhibitors in the dorsal cochlear nucleus. II. Model
      calculations of the responses to complex sounds.
AB  - In a previous modeling study of signal processing in the dorsal cochlear nucleus
      [Reed and Blum, J. Acoust. Soc. Am 96, 1442-1453 (1997)] it was shown that
      inclusion of a wideband inhibitor (WBI) greatly improved the fit between model
      response maps and the experimental response maps of type IV units to pure tones.
      In this study we examine the effect of the WBI on the responses to complex sound
      stimuli such as broadband noise (BBN), notch noise, noise bands, and band/notch
      combinations. A new and more realistic model for auditory nerve (AN) response in
      the presence of different levels of noise is used. It is shown that one can
      explain and understand the qualitative features of virtually all the published
      data on type II and type IV unit responses to BBN, notch noise and noise bands.
      The monotone decreasing response of the maximum firing rate of type II units to
      noise bands of increasing width that is observed experimentally occurs in the
      model due to the increasing inhibition of type II cells by the WBI. Similarly,
      the various nonmonotone patterns of maximum firing rate of type IV units to noise
      bands of increasing width is shown to arise from the complex and highly nonlinear
      effects of inhibition from the type II to type IV and the WBI to type IV cells
      and the nonlinear direct excitation from the AN to the type IV cells. A number of
      experiments using double notches, double noise bands, or notch-noise band pairs
      are suggested which, by comparison with model results, would allow one to infer
      probable connectional patterns between type II and type IV units and between the
      WBI units and the type IV units.

PMID- 9566323
TI  - Basilar membrane nonlinearity and loudness.
AB  - Loudness matching functions for tones for persons with one shifted-threshold ear
      (hearing loss and noise-shifted thresholds) and one ear within normal limits were
      used to derive the presumed basilar membrane (BM) input-output (I/O) function in
      a normal ear. The comparison was made by assuming that the BM I/O function for
      the ear with the cochlear threshold shift has a slope of one (a linearized
      cochlea). The function for the normal ear was derived from the loudness matching
      function based on this assumption. Comparisons were made for archival basilar
      membrane data [M. A. Ruggero, N. C. Rich, A. Recio, S. S. Narayan, and L. Robles,
      J. Acoust. Soc. Am. 101, 2151-2163 (1997)] for chinchilla and archival loudness
      matches for long-duration tones for persons with various degrees of cochlear
      hearing loss [F. Miskolczy-Fodor, J. Acoust Soc. Am. 32, 486-492 (1960)].
      Comparisons were made also between BM I/O functions and ones derived from
      loudness matches for persons with unilateral hearing loss simulated by broadband
      noise. The results show a close resemblance between the basilar membrane I/O
      function and the function derived from loudness matches for long-duration tones,
      even though the comparison was between human and chinchilla data. As the degree
      of threshold shift increases from 40 to 80 dB, the derived BM I/O functions
      become shallower, with slopes for losses of 60 dB or more falling in the range of
      values reported for physiological data. Additional measures with short-duration
      tones in noise show that the slope of the loudness function and the slope of the
      derived basilar membrane I/O function are associated with the behavioral
      threshold for the tone. The results for long-duration tones suggest a
      correspondence between BM displacement and loudness perception in cases of
      recruitment, but the relation between the degree of loss and the amount of BM
      compression and the relation between signal duration and compression suggests
      that other factors, such as the neural population response, may play a role.

PMID- 9566324
TI  - Interactions of forward and simultaneous masking in intensity discrimination.
AB  - Intensity coding mechanisms are explored in a paradigm involving both forward and
      simultaneous masking. For intensity discrimination of 1000-Hz pure tone in quiet,
      a near-miss to Weber's law is observed. However, as more stimulus components are
      added to this relatively simple experiment, interactions among components produce
      a more complex pattern of results. An intense forward masker, while not causing
      any threshold shift for the test tone, produces a nonmonotonic intensity
      discrimination function ["the midlevel hump," Zeng et al., Hearing Res. 55, 223
      230 (1991)]. The midlevel hump can be removed by the presence of additional
      notched noise [Plack and Viemeister, J. Acoust. Soc. Am. 92, 1902-1910 (1992)] or
      narrow-band noise whose level is increased along with the test tone's standard
      level. The same midlevel hump can also be enhanced by a fixed-low-level notched
      noise or a high-level, high-pass noise which causes minimal masking at the test
      frequency. Interactions of forward masking and simultaneous masking present a
      serious problem for a clear interpretation of these results. For example, the
      notched noise was originally intended to restrict off-frequency listening, but on
      frequency masking compromised this original purpose and confounded the
      interpretation of the notched noise effects. By measuring systematically the
      growth-of-masking functions, the present study identified various interactions of
      forward and simultaneous masking and clarified the role of off-frequency
      listening in forward-masked intensity discrimination. Both peripheral and central
      mechanisms may have contributed to the occurrence, reduction and enhancement of
      the midlevel hump under these masking conditions.

PMID- 9566325
TI  - Intensity discrimination for precedence effect stimuli.
AB  - When two identical stimuli are presented from two loudspeakers with a brief delay
      between them, a single image is heard near the source of the leading sound. The
      delayed sound or echo appears to be suppressed whereas the preceding sound
      determines perceived location, hence the name, the precedence effect. This study
      investigated normal-hearing listeners' sensitivity to changes in the intensity of
      the lagging sound. Pairs of 2-ms white noise bursts, with a 2-ms delay between
      the onsets of lead and lag, were presented from two loudspeakers 45 degrees left
      and right of midline in an anechoic chamber. A 2AFC procedure was used to test
      discrimination of intensity changes in the lead, lag, and both sounds together.
      The untreated results showed discrimination to be poorest for changes in the lag
      stimulus. However, when the intensity differences were transformed into
      predictions of equivalent monaural level based on KEMAR measurements and binaural
      loudness summation, discrimination for the lag was equal to the other two
      conditions. A follow-up experiment found that listeners were highly sensitive to
      the presence of the lag, more sensitive than would be predicted from loudness
      changes. It is concluded that the precedence effect does not consist of a general
      suppression or attenuation of the lagging sound, but rather that suppression may
      be limited to directionality cues.

PMID- 9566326
TI  - Ripple density resolution for various rippled-noise patterns.
AB  - Ripple-density resolution was measured in normal humans using rippled noise with
      a phase-reversal test. The principle of the test was to find the highest ripple
      density at which an interchange of spectral peak and trough positions (the phase
      reversal) is detectable. Different rippled noise patterns were used: (i) either
      frequency-proportional or constant ripple spacing; (ii) various bandwidth; and
      (iii) either steep or shallow slopes of the spectrum envelope. When tested with
      frequency-proportional rippled noise, ripple-density resolution as expressed in
      relative units (the center frequency to ripple spacing ratio) little depended on
      frequency within a range of 1 to 8 kHz: from 11.4 at 1 kHz to 14.9 at 8 kHz, mean
      13.1. These values were virtually independent on noise bandwidth. When tested
      with constant ripple spacing, the resolution was of similar values taking the
      relative ripple density at the lower part of the passband. Being measured by
      noise with steep spectral edges, the resolution was five units higher than it was
      for shallow-enveloped spectra, thus suggesting some edge effects at the spectrum
      boundaries. The resolution values obtained were about twice higher than those
      predicted by peripheral auditory filter tuning.

PMID- 9566327
TI  - Temporal processing of the pitch of complex tones.
AB  - The effect of tone duration on fundamental frequency (F0) discrimination is
      greater for complexes containing unresolved harmonics than for those containing
      resolved harmonics [Plack and Carlyon, J. Acoust. Soc. Am. 98, 1355-1364 (1995)].
      Three experiments explored this effect further. The first experiment measured
      sensitivity (as d') to fundamental frequency (F0) differences for two complexes,
      both with an F0 of 250 Hz. The first complex was low-pass filtered at 1875 Hz to
      create a resolved complex and the second was bandpass filtered between 5500 and
      7500 Hz to create an unresolved complex. The harmonics for the resolved complex
      were selected so that no two harmonics were the same between the two observation
      intervals. Performance for both complexes was measured for tone durations of 20,
      40, 80, and 160 ms. For the unresolved complex, the effect of duration was
      greater than that for the resolved complex and greater than the predictions of a
      "multiple-looks" model assuming either peripheral (before sampling) or central
      (after combining samples) sources of variance. The second experiment replicated
      these results using an F0 of 62.5 Hz with the cutoff frequencies of the bandpass
      filters divided by four, confirming that the effect is related to resolvability
      and not to spectral region. In the final experiment, F0 discrimination for pairs
      of complexes separated by a temporal gap was measured relative to that for one
      complex. Performance for the resolved and unresolved complexes was similar: Very
      little effect of gap duration was observed and the results were consistent with
      the predictions of the peripheral-variance multiple-looks model. Taken together,
      the results suggest that the pitch mechanism for resolved harmonics uses a
      relatively short sampling window of around 20 ms, while the mechanism for
      unresolved harmonics may use a more complex strategy for optimizing the
      combination of information over time, perhaps involving a flexible integration
      time.

PMID- 9566328
TI  - "Central" auditory gap detection: a spatial case.
AB  - Normal listeners were tested for their temporal auditory gap detection thresholds
      using free-field presentation of white-noise stimuli delivered from the left (L)
      and right (R) poles of the interaural axis. The noise bursts serving as the
      leading and trailing markers for the silent period were presented in either the
      same (LL,RR) or different (LR,RL) auditory locations. The duration of the leading
      marker was a second independent variable. Gap thresholds for stimuli in which the
      markers had the same location were low, and usually were independent of the
      duration of the leading marker. Gap thresholds for the LR and RL conditions were
      longer. These gap thresholds were sensitive to the duration of the leading
      marker, and increased as the leading marker duration decreased. This finding is
      consistent with the hypothesis that a relative timing operation mediates gap
      detection when the markers activate different perceptual channels. The present
      data suggest that this timing process can operate on perceptual channels emerging
      from central nervous system processing.

PMID- 9566329
TI  - Inter-individual differences in binaural detection of low-frequency or high
      frequency tonal signals masked by narrow-band or broadband noise.
AB  - Detection thresholds for either 500-Hz tones or 4-kHz tones were measured for a
      group of 19 listeners utilizing the interaural configurations NoSo and NoS pi.
      Both broadband (100-8500 Hz) noises and narrow-band (50-Hz-wide) noises served as
      maskers. In addition, direct measures of the listeners' sensitivities to changes
      in interaural temporal differences (ITDs) and interaural intensitive differences
      (IIDs) were measured using 400-Hz-wide noises centered at 500 Hz or 4 kHz. A
      rather large range of inter-individual differences in threshold was observed for
      4-kHz tonal signals masked by narrow-band noise in the NoS pi configuration. This
      result is consistent with several sets of data from our previous experiments
      conducted over more than a decade. A broad range of thresholds was also obtained
      for 500-Hz tonal signals masked by narrow-band noise in the NoS pi configuration.
      This outcome, coupled with the fact that the use of a broadband masker did not
      yield a large distribution of thresholds for the detection of a 500-Hz tone
      masked by a broad band of noise, suggests that it is the use of a narrow-band
      masker, per se, that results in a large range of thresholds. Statistical analyses
      revealed that thresholds in the NoS pi detection tasks were not highly correlated
      with thresholds measured in the ITD- and the IID-discrimination tasks.
      Nevertheless, the five listeners who were the most sensitive in the narrow-band
      NoS pi detection and the five listeners who were the least sensitive in the
      narrow-band NoS pi detection tasks were those who were the most and least
      sensitive, respectively, to changes in ITDs and to changes in IIDs.

PMID- 9566330
TI  - Effects of sensorineural hearing loss on interaural discrimination and virtual
      localization.
AB  - Cross-frequency binaural processing was investigated in listeners with normal
      hearing (NH) and with bilateral high-frequency sensorineural hearing impairment
      (IH). In experiment 1 just-noticeable-differences for interaural time and
      interaural intensity were measured using 1/3-octave narrow-band noises (NBNs)
      centered at 0.5 and 4 kHz. These stimuli were presented in isolation and in
      different cross-frequency interaural combinations. IH listeners displayed the
      best interaural time discrimination when the 0.5-kHz NBN was dichotic and the
      best intensity discrimination when both bands were dichotic. Both NH listeners
      (time) and IH listeners (time and intensity) displayed the poorest interaural
      discrimination when the NBNs were presented simultaneously with interaural
      differences in only the 4-kHz NBN (0.5 kHz NBN dichotic). Localization accuracy
      was measured in experiment 2 using the 0.5- and 4-kHz NBNs in isolation and with
      0.5-kHz target/4-kHz interferer and 4-kHz target/0.5-kHz interferer conditions.
      Best localization of NH and IH subjects was seen for the 0.5-kHz target, with or
      without an interferer. Poorest localization of IH subjects was observed for the 4
      kHz target and 0.5-kHz interferer. Results suggest that for these IH subjects,
      localization is most difficult when they are forced to rely on interaural
      information in a higher-frequency region with conflicting interaural information
      at low frequencies.

PMID- 9566331
TI  - Diotic and dichotic detection using multiplied-noise maskers.
AB  - Detection thresholds were measured with a multiplied-noise masker that was in
      phase in both ears and a sinusoidal signal which was either in phase or out of
      phase (NoSo and NoS pi conditions). The masker was generated by multiplying a low
      pass noise with a sinusoidal carrier. The signal was a sinusoid with the same
      frequency as the carrier and a constant phase offset, theta, with respect to the
      carrier. By adjusting the phase offset, the stimulus properties were varied in
      such a way that only interaural time delays (theta = pi/2) or interaural
      intensity differences (theta = 0) were present within the NoS pi stimulus.
      Thresholds were measured at a center frequency of 4 kHz as a function of
      bandwidth for theta = pi/2 and for theta = 0. In a second experiment thresholds
      were measured for a bandwidth of 25 Hz as a function of the center frequency. The
      results show that narrow-band BMLDs at 4 kHz can amount to 30 dB for the theta =
      0 condition. For this condition, narrow-band BMLDs are also reasonably constant
      across frequency, in contrast to results obtained with standard Gaussian-noise
      maskers. For theta = pi/2, BMLDs are restricted to the frequency region below 2
      kHz provided that the masker is narrow band, but BMLDs of up to 15 dB are found
      at 4 kHz if the masker is 50 Hz or wider. The frequency dependence of the
      binaural thresholds seems to be best explained by assuming that the stimulus
      waveforms are compressed before binaural interaction.

PMID- 9566332
TI  - Radio frequency hearing: electrostrictive detection and bone conduction.
AB  - A hearing aid patented by C. R. Schafer and supposedly based on detection of an
      amplitude-modulated carrier wave in the auditory cortex was re-examined. It is
      shown here that the hearing aid actually works by bone conduction of sound. It is
      concluded that detection of the modulation signal occurs by electrical
      nonlinearities and electrostriction in the bones of the face and skull.

PMID- 9566333
TI  - Auditory and linguistic factors in the perception of voice offset time as a cue
      for preaspiration.
AB  - Previous research [J. Pind, Acta Psychol. 89, 53-81 (1995)] has shown that
      preaspiration in Icelandic, an [h]-like sound inserted between a vowel and the
      following closure, can be cued by Voice Offset Time (VOffT), a speech cue which
      is the mirror image of Voice Onset Time (VOT). Research has also revealed that
      VOffT is much more sensitive to the duration of the neighboring vowel than is VOT
      [J. Pind, Q. J. Exp. Psychol. 49A, 745-764 (1996)]. This paper explores the
      hypothesis that it is primarily the perceived quantity of the vowel that is
      responsible for the effect of the vowel on the perception of preaspiration. This
      hypothesis is based on the linguistic fact that preaspiration can only follow a
      phonemically short vowel. This linguistic hypothesis is contrasted with an
      auditory hypothesis in terms of forward masking. Perceptual experiments show that
      the perceptual boundaries for preaspiration can be affected either by changing
      the preceding vowel's duration or its spectrum. If the spectrum of the vowel
      changes towards that of a long vowel, longer VOffT's are needed for listeners to
      perceive preaspiration, thus lending support to the linguistic hypothesis.

PMID- 9566334
TI  - Acoustical and physical dynamics of the diatonic harmonica.
AB  - The harmonica is arguably the most widely played instrument in the world, yet
      there is a surprising paucity of published studies of its acoustics or physical
      dynamics. The typical diatonic harmonica and the physical forces involved in its
      natural function are described, and simple observations of the harp's functions
      are reported. The speaking of the reeds, naturally, when producing a bend, and
      when speaking as an overblow or overdraw is discussed and investigated by simple
      stopping of the reeds, by videostroboscopic analysis, and by recording vibration
      of the reeds with displacement gauges. The reeds of the ten hole harmonica can be
      made to vibrate at varying frequencies depending on the size and shape of the
      player's vocal tract. Three different modes of speaking from each hole and its
      pair of reeds are revealed and studied: first, naturally in a closing mode,
      either blown or drawn; second, as a bend, either blown or drawn, with pitch in
      the interval between the two notes in the hole; and third, as an overblow or
      overdraw in an opening mode with a pitch outside the interval between the two
      natural notes of the hole. This dynamic interaction allows the player to speak
      with the instrument perhaps as with no other.

PMID- 9566335
TI  - Broadband measurements of phase velocity in Albunex suspensions.
AB  - The phase velocities in suspensions of Albunex, an ultrasound contrast agent, are
      determined using the technique of broadband phase spectroscopy. In these
      suspensions, phase velocities were measured as a function of Albunex
      concentration in Isoton II (buffered saline). The dispersion over the measurement
      bandwidth (1-15 MHz) grew with increasing Albunex concentration, exhibiting a 221
      m/s change (17% increase) in phase velocity between 1.0 and 3.8 MHz at the
      highest concentration reported (32 microL Albunex/8 mL Isoton). The dispersion
      behavior of the Albunex suspensions is described using a model of encapsulated
      gas bubbles. The influence of the dispersion in Albunex on broadband pulses is
      discussed, as well as the potential impact this dispersion may have on the
      formation of ultrasonic images of the heart.

PMID- 9566336
TI  - Target flutter rate discrimination by bats using frequency-modulated sonar
      sounds: behavior and signal processing models.
AB  - This study utilized psychophysical data and acoustical measurements of sonar
      echoes from artificial fluttering targets to develop insights to the information
      used by FM bats to discriminate the wingbeat rate of flying insects. Fluttering
      targets were produced by rotating blades that moved towards the bat, and the
      animal learned to discriminate between two rates of movement, a reference rate
      (30 or 50 Hz) and a slower, variable rate. Threshold discrimination performance
      depended on the rotation rate of the reference target, with a difference value of
      9 Hz for the reference rate of 30 Hz and 14 Hz for the reference rate of 50 Hz.
      Control experiments demonstrated that the bats used sonar echoes from the moving
      targets to perform the discrimination task. Acoustical measurements showed that
      the moving target produced a Doppler shift in the echo and a concomitant change
      in the arrival time of each frequency in the linear period FM sweep. The
      difference in delay between echoes from moving and stationary parts varied
      linearly with flutter rate and depended on the characteristics of the bat's sonar
      sounds. Simulations also showed a reduction in average echo bandwidth with
      increasing flutter rate, which may account for a higher delay discrimination
      threshold using the 50-Hz reference rate. This work suggests that Doppler-induced
      changes in echo delays produced by fluttering targets may contribute to the FM
      bat's perception of flying insect prey.

PMID- 9566337
TI  - Broadband spectra of seismic survey air-gun emissions, with reference to dolphin
      auditory thresholds.
AB  - Acoustic emissions from a 2120 cubic in air-gun array were recorded through a
      towed hydrophone assembly during an oil industry 2-D seismic survey off the West
      Wales Coast of the British Isles. Recorded seismic pulses were sampled,
      calibrated, and analyzed post-survey to investigate power levels of the pulses in
      the band 200 Hz-22 kHz at 750-m, 1-km, 2.2-km, and 8-km range from source. At 750
      m range from source, seismic pulse power at the 200-Hz end of the spectrum was
      140 dB re: 1 microPa2/Hz, and at the 20-kHz end of the spectrum seismic pulse
      power was 90 dB re: 1 microPa2/Hz. Although the background noise levels of the
      seismic recordings were far in excess of ambient, due to the proximity of engine,
      propeller, and flow sources of the ship towing the hydrophone, seismic power
      dominated the entire recorded bandwidth of 200 Hz-22 kHz at ranges of up to 2 km
      from the air-gun source. Even at 8-km range seismic power was still clearly in
      excess of the high background noise levels up to 8 kHz. Acoustic observations of
      common dolphins during preceding seismic surveys suggest that these animals
      avoided the immediate vicinity of the air-gun array while firing was in progress,
      i.e., localized disturbance occurred during seismic surveying. Although a general
      pattern of localized disturbance is suggested, one specific observation revealed
      that common dolphins were able to tolerate the seismic pulses at 1-km range from
      the air-gun array. Given the high broadband seismic pulse power levels across the
      entire recorded bandwidth, and known auditory thresholds for several dolphin
      species, we consider such seismic emissions to be clearly audible to dolphins
      across a bandwidth of tens on kilohertz, and at least out to 8-km range.

PMID- 9566338
TI  - Automated recognition of bird song elements from continuous recordings using
      dynamic time warping and hidden Markov models: a comparative study.
AB  - The performance of two techniques is compared for automated recognition of bird
      song units from continuous recordings. The advantages and limitations of dynamic
      time warping (DTW) and hidden Markov models (HMMs) are evaluated on a large
      database of male songs of zebra finches (Taeniopygia guttata) and indigo buntings
      (Passerina cyanea), which have different types of vocalizations and have been
      recorded under different laboratory conditions. Depending on the quality of
      recordings and complexity of song, the DTW-based technique gives excellent to
      satisfactory performance. Under challenging conditions such as noisy recordings
      or presence of confusing short-duration calls, good performance of the DTW-based
      technique requires careful selection of templates that may demand expert
      knowledge. Because HMMs are trained, equivalent or even better performance of
      HMMs can be achieved based only on segmentation and labeling of constituent
      vocalizations, albeit with many more training examples than DTW templates. One
      weakness in HMM performance is the misclassification of short-duration
      vocalizations or song units with more variable structure (e.g., some calls, and
      syllables of plastic songs). To address these and other limitations, new
      approaches for analyzing bird vocalizations are discussed.

PMID- 9566340
TI  - Low-frequency amphibious hearing in pinnipeds: methods, measurements, noise, and
      ecology.
AB  - Aerial low-frequency (100-6400 Hz) hearing thresholds were obtained for one
      California sea lion (Zalophus californianus), one harbor seal (Phoca vitulina),
      and one northern elephant seal (Mirounga angustirostris). Underwater thresholds
      over a similar frequency range (75-6300 or 6400 Hz) were obtained for these three
      animals in addition to another California sea lion. Such data are critical, not
      only for understanding mechanisms about amphibious hearing and relating them to
      pinniped ecology and evolution, but also for identifying species at risk to man
      made noise in the marine environment. Under water, the elephant seal was most
      sensitive, followed by the harbor seal and the sea lions. In air, the harbor seal
      was most sensitive, followed by the older of the two sea lions and the elephant
      seal. The following trends emerged from comparisons of each subject's aerial and
      underwater thresholds: (a) the sea lion (although possessing some aquatic
      modifications) is adapted to hear best in air; (b) the harbor seal hears almost
      equally well in air and under water; and (c) the elephant seal's auditory system
      is adapted for underwater functioning at the expense of aerial hearing
      sensitivity. These differences became evident only when aerial and underwater
      thresholds were compared with respect to sound pressure rather than intensity.
      When such biologically relevant comparisons are made, differences in auditory
      sensitivity can be shown to relate directly to ecology and life history.

PMID- 9566339
TI  - Acoustic and articulatory correlates of stop consonants in a parrot and a human
      subject.
AB  - General acoustic patterns in productions of American English stops /p,b,t,d,k,g/
      by a Grey parrot (Psittacus erithacus) and his primary human trainer are
      identified. Comparisons demonstrated both differences (coherence of voicing
      [/p,t,k/ and /b,d,g/] and place [/p,b/, /t,d/, and /k,g/] subsets, predictive
      power of measures related to F1 and F3) and similarities (categorical
      distinctions among stop consonants) in acoustic properties of psittacine and
      human speech. The authors suggest how acoustic data might be correlated with
      articulatory events in the parrot. Our data are also compared with speech from a
      mynah (Gracula religiosa). Because humans perceive and correctly label psittacine
      stop consonants despite differences in avian and human articulatory and acoustic
      parameters, our findings (a) further expand our initial work with vowels
      [Patterson and Pepperberg, J. Acoust. Soc. Am. 96, 634-648 (1994)], (b)
      corroborate findings suggesting that the perceptual discontinuities exploited by
      speech may be accessible to various sensory systems, and (c) challenge the notion
      that human speech production is a unique process.

PMID- 9566343
TI  - Piezoelectrical shear-force distance control in near-field optical microscopy for
      biological applications.
AB  - We present a piezoelectrical shear-force distance control setup for scanning near
      field optical microscopy. The setup is compact and tip exchange is easy. The
      topographical sensitivity is comparable to optical feedback systems. With an
      acceptable vibration amplitude of 5-10 nm we obtained a topographical resolution
      of 5 pm/square root of Hz. Because there is no laser necessary for tip position
      feedback, there is no extraneous light to interfere with spectroscopic and other
      low-light level experiments. Our technique permits measurements of soft
      biological samples in aqueous solution, which opens up many possible applications
      of near-field optical microscopy in biology and medicine.

PMID- 9566344
TI  - Tuning fork shear-force feedback.
AB  - Investigations have been performed on the dynamics of a distance regulation
      system based on an oscillating probe at resonance. This was examined at a tuning
      fork shear-force feedback system, which is used as a distance control mechanism
      in near-field scanning optical microscopy. In this form of microscopy, a tapered
      optical fiber is attached to the tuning fork and scanned over the sample surface
      to be imaged. Experiments were performed measuring both amplitude and phase of
      the oscillation of the tuning fork as a function of driving frequency and tip
      sample distance. These experiments reveal that the resonance frequency of the
      tuning fork changes upon approaching the sample. Both the amplitude and the phase
      of the tuning fork can be used as distance control parameter in the feedback
      system. Using the amplitude a second-order behavior is observed, while with phase
      only a first-order behavior is observed. Numerical calculations confirm these
      observations. This first-order behavior results in an improved stability of the
      feedback system. As an example, a sample consisting of DNA strands on mica was
      imaged which showed the height of the DNA as 1.4 +/- 0.2 nm.

PMID- 9566345
TI  - Near-field fluorescence microscopy of cells.
AB  - We demonstrate the surface sensitivity of near-field scanning optical microscopy
      by fluorescence imaging of membrane and bulk proteins in cells. We discuss
      instrument design considerations for successful cell-biology work with NSOM and
      show that the technique is most suited for studying membrane proteins.

PMID- 9566346
TI  - Near-field optical and shear-force microscopy of single fluorophores and DNA
      molecules.
AB  - Photodynamics of individual fluorescence molecules has been studied using an
      aperture-type near-field scanning optical microscope with two channel
      fluorescence polarisation detection and tuning fork shear-force feedback. The
      position of maximum fluorescence from individual molecules could be localised
      with an accuracy of 1 nm. Dynamic processes such as translational and rotational
      diffusion were observed for molecules adsorbed to a glass surface or embedded in
      a polymer host. The in-plane molecular dipole orientation could be determined by
      monitoring the relative contribution of the fluorescence signal in the two
      perpendicular polarised directions. Rotational dynamics was investigated on 10 ms
      1000 s timescale. Shear-force phase feedback was used to obtain topographic
      imaging of DNA fragments, with a lateral and vertical resolution comparable to
      scanning force microscopy. A DNA height of 1.4 nm has been measured, an
      indication of the non-disturbing character of the shear force mechanism.

PMID- 9566347
TI  - Near-field optical imaging of unstained bacteria: comparison with normal atomic
      force and far-field optical microscopy in air and aqueous media.
AB  - Simultaneous near-field scanning optical and atomic force imaging of bacteria is
      presented. The bacteria imaged in these studies were unstained. The near-field
      optical images had excellent signal-to-noise and showed excellent contrast even
      in these unstained specimens. The images obtained were interpreted in terms of
      the images that have been obtained by transmission electron microscopy and X-ray
      imaging. The results show that bacterial near-field optical imaging is going to
      be a very important tool in the arsenal of the bacteriologist both in terms of
      understanding the fundamental processes in the life cycle of bacteria with and
      without cytochemical staining and in terms of clinical diagnostic applications.

PMID- 9566349
TI  - Natural anti-immunoglobulin autoantibodies: irrelevant by-products or
      immunoregulatory molecules?
AB  - Anti-immunoglobulin autoantibodies (anti-Ig auto-Abs), particularly IgM-anti-IgG
      (classical rheumatoid factor), have been studied mainly in the context of
      rheumatoid arthritis. In this article we focus on other members of the anti-Ig
      family, including the natural IgG-anti-F(ab')2 auto-Ab, and look for clinical and
      experimental findings supporting a role of these antibodies in the regulation of
      the immune response. We discuss the evidence for suppression of auto- and
      alloreactive B cells by IgG-anti-F(ab')2 auto-Ab and the role of this Ab in the
      pathogenesis of certain diseases, such as autoimmune hemolytic anemia. The
      structure of the antibody's antigen-binding site was clarified by isolating the
      VL and VH gene segments from the cDNA of B cells. Sequence analyses revealed
      germline gene identity of VL chains and 88% homology with the closest germline
      gene of VH chains. Finally, we discuss hypothetical models concerning the
      immunoregulatory role of natural anti-Ig auto-Abs.

PMID- 9566348
TI  - Molecular mechanisms of immunoglobulin E regulation.

PMID- 9566350
TI  - Lactobacillus casei inhibits antigen-induced IgE secretion through regulation of
      cytokine production in murine splenocyte cultures.
AB  - BACKGROUND: Lactobacillus casei is a nonpathogenic gram-positive bacterium widely
      used in dairy products and has been shown to enhance the cellular immunity of the
      host. METHODS: To examine the inhibitory effect of L. casei on IgE production,
      splenocytes obtained from ovalbumin (OVA)-primed BALB/c mice were restimulated in
      vitro with the same antigen in the presence of heat-killed L. casei. The effect
      of this bacterium on T helper (Th) phenotype development was also examined with
      naive T cells from OVA-specific T cell receptor-transgenic mice. RESULTS: L.
      casei induced IFN-gamma, but inhibited IL-4 and IL-5 secretion, and markedly
      suppressed total and antigen-specific IgE secretion by OVA-stimulated
      splenocytes. The inhibitory effect of L. casei on IgE, IL-4, and IL-5 production
      was partially abrogated by addition of neutralizing antibody to IFN-gamma.
      Augmented IL-12 production was also observed in the cell cultures containing L.
      casei, and anti-IL-12 monoclonal antibody completely restored the IgE, IL-4, and
      IL-5 production to the control levels. The IL-12 augmentation by L. casei was
      macrophage-dependent. The Th cell development assay showed the ability of L.
      casei to induce Th1 development preferentially. This effect was also completely
      blocked by anti-IL-12 antibody. CONCLUSIONS: This is the first demonstration that
      a nonpathogenic microorganism, L. casei, can inhibit antigen-induced IgE
      production through induction of IL-12 secretion by macrophages. The findings
      suggest a potential use of this organism in preventing IgE-mediated allergy.

PMID- 9566351
TI  - Histamine-stimulated cytokine secretion from human conjunctival epithelial cells:
      inhibition by the histamine H1 antagonist emedastine.
AB  - The present studies demonstrate that histamine induces the secretion of IL-6, IL
      8 and GM-CSF from human conjunctival epithelial cells in a dose- and time
      dependent manner. The histamine antagonists emedastine (H1), ranitidine (H2) and
      thioperamide (H3) were evaluated for their ability to inhibit secretion of these
      cytokines. Emedastine potently inhibited histamine-induced IL-6, IL-8 and GM-CSF
      secretion with mean IC50 values of 2.23, 3.42 and 1.50 nM, respectively.
      Ranitidine and thioperamide failed to inhibit cytokine secretion over a wide dose
      range. These data suggest that mast cell derived histamine may stimulate
      inflammatory cytokine production in allergic conjunctivitis via activation of
      epithelial cell H1 receptors. The histamine H1 antagonist emedastine potently
      inhibits this response.

PMID- 9566352
TI  - Purification of filaggrin from human epidermis and measurement of antifilaggrin
      autoantibodies in sera from patients with rheumatoid arthritis by an enzyme
      linked immunosorbent assay.
AB  - BACKGROUND: The so-called antikeratin antibody (AKA) and the antiperinuclear
      factor (APF) that recognize proteins related to human epidermal filaggrin belong
      to the most specific serological markers of rheumatoid arthritis (RA). However,
      assays for the detection of AKA and APF are currently based on
      immunofluorescence, a method that is subject to arbitrary interpretation and
      inadequate standardization of the substrates. METHODS: Proteins extracted from
      human epidermis were separated by reversed-phase high-performance liquid
      chromatography (HPLC). Filaggrin-containing fractions, identified in
      immunoblotting by monoclonal antifilaggrin antibodies, were then subjected to gel
      filtration HPLC and, finally, to a second reversed-phase HPLC step. Tryptic
      digestion, amino acid sequencing and mass spectrometry were used to confirm the
      identity of the purified protein. Filaggrin was used as antigen in enzyme-linked
      immunosorbent assay (ELISA) to measure IgG class antifilaggrin antibodies.
      RESULTS: The filaggrin preparation obtained gave a single band in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, binding monoclonal antifilaggrin
      antibody in immunoblotting. Amino acid sequences of all 10 tryptic peptides
      analyzed were shown to originate from human filaggrin. Antifilaggrin antibody
      levels exceeded the 99th percentile level of 100 middle-aged blood donors in
      26/55 (47%) RA sera. At a similar cutoff level 28/55 (51%) of the RA sera were
      positive in the AKA test. Of the 26 antifilaggrin-positive sera, 21 were also AKA
      positive. CONCLUSION: Human filaggrin can be purified by standard biochemical
      techniques, despite the heterogeneity of the protein, and used in ELISA for
      testing autoantibodies to filaggrin. The sensitivity of the assay equals that of
      the AKA test.

PMID- 9566353
TI  - Experimental monkey model sensitized with mite antigen.
AB  - BACKGROUND: Monkeys are considered to have an immune system very similar to that
      of humans, as compared with mice, rats, and guinea pigs. Although primate
      allergic models to several pollen allergens have been developed, no model of
      house dust mite allergy has been reported. In this study, we attempted to induce
      type I allergy to mite allergens in rhesus monkeys. METHODS: Six rhesus monkeys
      were immunized subcutaneously with crude mite extract adsorbed on aluminum
      hydroxide for 4 months. Then 5 monkeys positive for IgE production to mite
      extract were further immunized subcutaneously and conjunctivally with recombinant
      Der f 2 (rDer f 2). The status of sensitization to mite extract and rDer f 2 in
      monkeys was examined before and after the immunization. Plasma antigen-specific
      IgE and IgG levels, cutaneous reaction, and histamine release from peripheral
      blood leukocytes were measured. After conjunctival immunization, immediate
      conjunctivitis and leukocyte influx into conjunctiva after rDer f 2 challenge
      were examined. RESULTS: After immunization with crude mite extract, 5 of 6
      sensitized monkeys showed IgE response to the mite, and 4 out of 5 rDer f 2
      sensitized monkeys exhibited IgE production to rDer f 2. Three monkeys sensitized
      with rDer f 2 showed immediate conjunctivitis and conjunctival eosinophilia after
      applying rDer f 2 to their eyes. Sensitized animals also showed IgG response to
      mite antigens. CONCLUSION: Four rhesus monkeys were positive for IgE production
      and allergic reactions to both mite extract and rDer f 2. These monkeys could
      represent a useful model for studying the development and regulation of house
      dust mite allergy.

PMID- 9566354
TI  - Distribution of small intestinal lesions in anaphylaxis of rats.
AB  - Hemorrhage and congestion were not uniformly distributed along the small
      intestine during systemic anaphylaxis in rats. Duodenum had little hemorrhage and
      congestion and the terminal ileum had even less. Maximum involvement occurred in
      jejunum of 13% of rats, in ileum of 47%, and in both jejunum and ileum of 40%.
      Sequential scoring along the entire length of small intestine revealed different
      patterns of distribution with more than one peak of intensity in some of the
      rats. Within a lesioned area, banding was common except where hemorrhage and
      congestion were so severe as to obliterate all patterns. Banding represented a
      gradient of injury with respect to the vascular supply. The pale stripes (less
      severe hemorrhage) contained the penetrating vessels derived from the terminal
      mesenteric arcades. The dark stripes (more severe hemorrhage) did not contain
      such vessels. In addition, the mesenteric side of the intestine was less affected
      than the antimesenteric side. This constituted a second gradient that might also
      be related to the distance from the vascular supply. In both instances, proximity
      to larger blood vessels had a protective effect. These two gradients and the
      variable sites and patterns of distribution have not been described previously in
      intestinal anaphylaxis. Gradients and the variability of the distribution of
      lesions in intestinal anaphylaxis should be considered in experiments on
      pathogenesis and altered function.

PMID- 9566355
TI  - Ultraviolet A radiation (320-400 nm) protects hairless mice from
      immunosuppression induced by ultraviolet B radiation (280-320 nm) or cis-urocanic
      acid.
AB  - T cell-mediated immune function, here measured as the contact hypersensitivity
      reaction, is readily suppressed by moderate exposure of mice to ultraviolet B
      (UVB) or solar-simulated radiation (SSUV), or by topical application of cis
      urocanic acid. The effect of ultraviolet A (UVA) radiation on immune function has
      been unclear. Here we have demonstrated that when UVA radiation from a
      fluorescent tube source was rigorously filtered to remove contaminating UVB
      radiation, it was immunologically innocuous at physiologically relevant doses.
      Furthermore, we have found that mice exposed to UVA radiation, either immediately
      after, or up to 24 h before, immunosuppressive treatment with either UVB
      radiation, SSUV or cis-urocanic acid, became refractory to the immunosuppression
      and retained more normal contact hypersensitivity. A greater UVA exposure
      reversed the immunosuppression more effectively. The results suggest that there
      are immunologically significant interactions between UV wavebands, and that UVA
      exposure may induce a relatively long-lived immunoprotective photoproduct, as yet
      unidentified, that can inhibit the activity of epidermal cis-urocanic acid and
      thus provide protection from photoimmunosuppression.

PMID- 9566356
TI  - Lacunes: small, deep cerebral infarcts. 1965.

PMID- 9566357
TI  - Magnetic resonance imaging in acute stroke: not ready for prime time.

PMID- 9566358
TI  - When you look for evidence and find too much: systematic reviews to the rescue.

PMID- 9566359
TI  - Subtle hippocampal malformation: importance in febrile seizures and development
      of epilepsy.

PMID- 9566360
TI  - Breast implants redux: this time with data.

PMID- 9566361
TI  - Dopa-responsive dystonia: some pieces of the puzzle are still missing.

PMID- 9566362
TI  - The pathogenesis of diffuse infiltrative lymphocytosis syndrome: an AIDS-related
      peripheral neuropathy.

PMID- 9566363
TI  - Levodopa: is toxicity a myth?
AB  - Whether a drug such as levodopa, which is prescribed for long periods, may be
      toxic is a legitimate and even indispensable question. The problem is no
      different from that posed by other drugs-such as calcium antagonists,
      antihypertensives, or hormones-normally prescribed for chronic diseases. What,
      however, is meant in this context by "toxic" (from the Greek toxicon, meaning
      poison)? Irrevocable damage such as cell loss should not be confused with
      reversible side effects resulting from cell dysfunction. Clinically or
      experimentally, levodopa has not been shown to accelerate neurodegeneration or
      cause permanent impairment of cell function in a manner that would result in
      irreversible side effects. These data have been reasonably well established in
      vivo in animals and humans, although preliminary studies suggesting that levodopa
      is a trophic factor remain unconfirmed. Like oxygen or calcium, levodopa can be
      toxic in vitro when it is present in high concentrations or in the absence of
      glial cells. However, glial cells are much more numerous than neurons in vivo, so
      these conditions cannot simply be extrapolated to three-dimensional brain
      structures in which protective interactions with the cellular environment abound.
      Because levodopa remains the most effective treatment available for Parkinson's
      disease, questions regarding timing or manner of administration of the drug
      should arise not because levodopa is toxic to nerve cells, but because it causes
      reversible side effects. When the elementary rules of substitutive therapy to
      provide maximum comfort while limiting side effects are followed, we need not
      fear that levodopa is dangerous unless the contrary is proven.

PMID- 9566364
TI  - Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute
      (<6.5 hour) ischemic stroke.
AB  - BACKGROUND: Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI are
      powerful new techniques for the assessment of acute cerebral ischemia. However,
      quantitative data comparing the severity of clinical neurologic deficit with the
      results of DWI or PWI in the earliest phases of stroke are scarce. Such
      information is vital if MRI is potentially to be used as an objective adjunctive
      measure of stroke severity and outcome. OBJECTIVE: The authors compared initial
      DWI and PWI lesion volumes with subsequent 24-hour neurologic deficit as
      determined by National Institutes of Health Stroke Scale (NIHSS) score in acute
      stroke patients. Initial DWI and PWI volumes were also compared with T2W MRI
      lesion volume at 1 week to assess the accuracy of these MRI techniques for the
      detection of acute cerebral ischemia. METHODS: Patients with stroke underwent MRI
      scanning within 6.5 hours of symptom onset. Lesion volumes on DWI and PWI were
      measured and compared with 24-hour NIHSS score. Initial DWI and PWI volumes were
      also compared with T2W lesion size at 1 week. RESULTS: There was a high
      correlation between 24-hour NIHSS score and lesion volume as determined by PWI (r
      = 0.96, p < 0.001) or DWI (r = 0.67, p = 0.03). A similar high correlation was
      seen between T2W stroke size at 7 days and initial DWI and PWI lesion size (r =
      0.99, p < 0.00001). CONCLUSIONS: Both DWI and PWI are highly correlated with
      severity of neurologic deficit by 24-hour NIHSS score. These findings may have
      substantial implications for the use of MRI scanning in the assessment and
      management of acute stroke patients.

PMID- 9566365
TI  - Efficacy of intra-arterial and intravenous prourokinase in an embolic stroke
      model evaluated by diffusion-perfusion magnetic resonance imaging.
AB  - OBJECTIVE: To explore the utility of intravenous (i.v.) prourokinase treatment,
      we compared intra-arterial (i.a.) and i.v. delivery in a rat embolic stroke
      model, using diffusion (DWI) and perfusion (PI) magnetic resonance imaging to
      assess in vivo effects on ischemic lesion evolution and reperfusion. BACKGROUND:
      Thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA)
      for acute ischemic stroke is useful during the initial hours after onset.
      Prourokinase is a novel thrombolytic agent with potential safety advantages in
      comparison to rt-PA. METHODS: Twenty-four male Sprague-Dawley rats were embolized
      with autologous blood clots into the middle cerebral artery territory and then
      randomly assigned at 30 minutes after embolization to a 2-hour bolus infusion
      with i.a. prourokinase, i.v. prourokinase, or vehicle. DWI and PI were performed
      before treatment and repeated during and at the end of the treatment. RESULTS: PI
      demonstrated that both i.a. and i.v. significantly improved the percentage of the
      ischemic hemisphere that was normally perfused when the 20-minute, pretreatment,
      and 145-minute after embolization time points were compared; in the control
      group, the hypoperfused volume increased over time. DWI disclosed that the
      ischemic lesion evolution slightly decreased in the i.a. group, remained stable
      in the i.v. group, and increased over time in the control group. Infarct volume
      by triphenyltetrazolium chloride (TTC) staining was significantly smaller in both
      treatment groups than controls. CONCLUSIONS: These results demonstrate that i.a.
      and i.v. therapy with prourokinase are equally effective in promoting reperfusion
      and inhibiting the development of focal ischemic injury in this rat embolic
      stroke model.

PMID- 9566366
TI  - Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a
      systematic review.
AB  - BACKGROUND AND PURPOSE: It has been reported that nimodipine reduces the
      frequency of secondary ischemia and improves outcome after aneurysmal SAH, but
      definitive evidence concerning all available calcium antagonists is lacking.
      METHODS: Systematic overview of randomized trials that were completed by January
      1996 compared calcium antagonists with control and started treatment within 10
      days after onset of subarachnoid hemorrhage (SAH) was performed. All calcium
      antagonists studied thus far (nimodipine, nicardipine, and AT877) were included.
      RESULTS: We analyzed 10 trials totaling 2756 patients. The relative risk (RR)
      reduction of poor outcome (death or dependency) was 16% (95% CI, 6 to 27%) and
      that of case fatality was 10% (95% CI, -6 to 25%). To prevent one poor outcome,
      19 (12 to 59) patients need to be treated. Calcium antagonists give a 33% (95%,
      CI 25 to 41) RR reduction in the frequency of ischemic neurologic deficit and a
      20% (95% CI, 11 to 28) RR reduction in the frequency of CT-scan documented
      cerebral infarction. Eight (6 to 11) patients need to be treated to prevent one
      ischemic neurologic deficit. In the analyses for nimodipine only, treatment was
      associated with a 24% RR reduction of poor outcome (95% CI, 12 to 38). To prevent
      one poor outcome, 13 (8 to 30) patients need to be treated with nimodipine. The
      RR reduction of angiographically detected cerebral vasospasm was statistically
      significant for AT877 (38%; 95% CI, 17 to 54%) and nicardipine (21%; 95% CI, 6 to
      34%) but not for nimodipine (9%; 95% CI, -2 to 19%). CONCLUSION: Calcium
      antagonists reduce the proportion of ischemic neurologic deficits and nimodipine
      improves overall outcome within 3 months of aneurysmal SAH; evidence for a
      reduction of poor outcome from all causes by nicardipine and AT877 is
      inconclusive. The intermediate factors by which nimodipine exerts its beneficial
      effect remain uncertain.

PMID- 9566367
TI  - Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke.
      NINDS rt-PA Stroke Study Group.
AB  - Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in
      stroke patients treated within 3 hours of symptom onset. The costs associated
      with this new treatment will be a factor in determining the extent of its
      utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature
      were used to estimate the health and economic outcomes associated with using tPA
      in acute stroke patients. A Markov model was developed to estimate the costs per
      1,000 patients eligible for treatment with tPA compared with the costs per 1,000
      untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo
      simulation) were performed to estimate the overall uncertainty of the model
      results. In the NINDS rt-PA Stroke Trial, the average length of stay was
      significantly shorter in tPA-treated patients than in placebo-treated patients
      (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home
      than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002).
      The Markov model estimated an increase in hospitalization costs of $1.7 million
      and a decrease in rehabilitation costs of $1.4 million and nursing home cost of
      $4.8 million per 1,000 eligible treated patients for a health care system that
      includes acute through long-term care facilities. Multiway sensitivity analysis
      revealed a greater than 90% probability of cost savings. The estimated impact on
      long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved
      over 30 years of the model per 1,000 patients. Treating acute ischemic stroke
      patients with tPA within 3 hours of symptom onset improves functional outcome at
      3 months and is likely to result in a net cost savings to the health care system.

PMID- 9566368
TI  - Cerebral infarction in young adults: the Baltimore-Washington Cooperative Young
      Stroke Study.
AB  - BACKGROUND: Few reports on stroke in young adults have included cases from all
      community and referral hospitals in a defined geographic region. METHODS: At 46
      hospitals in Baltimore City, 5 central Maryland counties, and Washington, DC, the
      chart of every patient 15 to 44 years of age with a primary or secondary
      diagnosis of possible cerebral arterial infarction during 1988 and 1991 was
      abstracted. Probable and possible etiologies were assigned following written
      guidelines. RESULTS: Of 428 first strokes, 212 (49.5%) were assigned at least one
      probable cause, 80 (18.7%) had no probable cause but at least one possible cause,
      and 136 (31.8%) had no identified probable or possible cause. Of the 212 with at
      least one probable cause, the distribution of etiologies was cardiac embolism
      (31.1%), hematologic and other (19.8%), small vessel (lacunar) disease (19.8%),
      nonatherosclerotic vasculopathy (11.3%), illicit drug use (9.4%), oral
      contraceptive use (5.2%), large artery atherosclerotic disease (3.8%), and
      migraine (1.4%). There were an additional 69 recurrent stroke patients.
      CONCLUSIONS: In this hospital-based registry within a region characterized by
      racial/ethnic diversity, cardiac embolism, hematologic and other causes, and
      lacunar stroke were the most common etiologies of cerebral infarction in young
      adults. Nearly a third of both first and recurrent strokes had no identified
      cause.

PMID- 9566369
TI  - Ischemic stroke after surgical procedures: clinical features, neuroimaging, and
      risk factors.
AB  - OBJECTIVE: To describe risk factors and explore mechanisms of ischemic strokes
      after general surgery. BACKGROUND: Strokes follow general surgery in about 0.08%
      to 2.9% of cases. Patients with previous cerebrovascular disease, atrial
      fibrillation, hypertension, advanced age, or atherosclerosis were found to have
      an increased risk. Knowledge of factors involved may guide physicians in
      determining the overall risk of surgery. METHODS: This case-control study was
      performed in a referral center. A total of 61 patients identified through a
      computerized database with ischemic strokes after surgical procedures-excluding
      heart, brain, vessels, or neck-between July 1986 and July 1996 were studied.
      Procedures included 11 urogenital, 16 gastrointestinal, 17 orthopedic, 12
      pulmonary, and 5 other. A total of 122 randomly selected controls were matched
      for age, sex, procedure, and year of procedure. Main outcome measures included
      arterial territory, timing, risk factors, and perioperative events. Differences
      were expressed as adjusted odds ratios (AOR) with 95% confidence limits (CL),
      using multivariate conditional logistic analyses for matched case-control design.
      RESULTS: Arterial territory included 37 middle cerebral artery, 11 posterior
      circulation, 7 borderzone, and 6 multiple. Median procedure to stroke interval
      was 2 days (range, 0 to 16); 10 patients had intraoperative strokes. Three major
      risk factors emerged: previous cerebrovascular disease (AOR 12.57, 95% CL
      2.14/73.70), chronic obstructive pulmonary disease (COPD) (7.51, 1.87/30.12), and
      peripheral vascular disease (PVD) (5.35, 1.25/22.94). After adding stroke-related
      factors, PVD (14.70, 2.01/107.71) and COPD (10.04, 1.90/53.14) remained the
      strongest variables; blood pressure (1.05, 1.01/1.10) and urea (1.04, 1.01/1.07)
      contributed slightly. Hypotension did not contribute. Four patients (6.6%) and no
      controls had diffuse intravascular coagulation (p = 0.01). Four stroke patients
      had myocardial infarction (6.6% versus 0%; p = 0.01). CONCLUSIONS: Ischemic
      strokes after general surgery most commonly occur after an asymptomatic interval.
      Previous cerebrovascular disease, COPD, and PVD greatly increase the risk.
      Hypotension rarely accounts for postoperative strokes. Major comorbidity of the
      patient at risk seems more important than complicating events during surgery.

PMID- 9566370
TI  - Brain-behavior correlations in hemispatial neglect using CT and SPECT: the
      Sunnybrook Stroke Study.
AB  - OBJECTIVE: Structural and functional lesion localization in patients with
      hemispatial neglect. DESIGN: Location and severity of brain damage on CT and
      SPECT correlated with neglect performance as assessed with a battery of drawings,
      line bisection, and line and shape cancellation subtests. PATIENTS: Participants
      included 120 consecutive stroke patients with a single right-hemisphere-damaged
      lesion on CT who were admitted to the Acute Stroke Care Unit at Sunnybrook Health
      Science Centre. Of these, 88 also had a SPECT. RESULTS: On CT, 82 patients with
      neglect (compared with 38 without neglect) had more extensive damage in the
      parietal and sensorimotor cortex and white matter fiber bundles, including the
      posterior-superior longitudinal and inferior-frontal fasciculi (p < 0.05).
      Parietal and anterior cingulate damage best predicted neglect score using the CT
      data (p < 0.05), and regional blood flow in the parietal cortex best predicted
      neglect score using the SPECT data (p < 0.05) after controlling for the influence
      of age and lesion size on multiple linear regression. CONCLUSIONS: Damage in the
      parietal and anterior cingulate cortex and posterior white matter fiber bundles
      correlated with hemispatial neglect. Combining structural- and functional-imaging
      techniques with neurobehavioral analysis can elucidate brain-behavior
      relationships.

PMID- 9566371
TI  - Hippocampal malformation as a cause of familial febrile convulsions and
      subsequent hippocampal sclerosis.
AB  - OBJECTIVE: One hypothesis proposes that a pre-existing alteration of medial
      temporal lobe structures contributes to febrile convulsions and subsequent
      hippocampal sclerosis (HS) in patients with temporal lobe epilepsy (TLE) and
      antecedent febrile convulsions. It is possible that such a structural alteration
      does not always lead to convulsions and may also be present in clinically
      unaffected relatives. METHODS: We tested this hypothesis by MRI investigation of
      23 members of two families, of whom 13 had experienced febrile convulsions and 10
      had not. One member of each family with febrile convulsions subsequently
      developed TLE. We compared the right/left ratios of hippocampal volumes (RHV)
      with 23 age- and sex-matched controls. Additionally, two independent raters
      assessed hippocampal signal intensity and pattern in T2- and fluid-attenuated
      inversion recovery images. RESULTS: Both TLE patients showed left HS. All
      subjects with febrile convulsions who did not develop epilepsy and six clinically
      unaffected relatives also showed asymmetric RHV (>3 standard deviation) but a
      normal hippocampal signal intensity. In all of these subjects, the left
      hippocampus was smaller. Visual inspection of these smaller hippocampi revealed
      blurred internal pattern or flat hippocampal bodies or both in one family and
      smaller hippocampal heads in the other. The pattern of HS in TLE patients showed
      a structural correlation with the abnormalities seen in their relatives. One
      subject with febrile convulsions had additional subcortical heterotopias.
      CONCLUSION: These findings suggest a subtle, pre-existing hippocampal
      malformation that may facilitate febrile convulsions and contribute to the
      development of subsequent HS.

PMID- 9566372
TI  - Epilepsy diagnosis and localization in patients with antecedent childhood febrile
      convulsions.
AB  - PURPOSE: A history of febrile convulsions (FC) is often obtained in patients
      presenting for surgical treatment of temporal lobe epilepsy (TLE), but it is not
      clear that preferential temporal localization of epilepsy is associated with
      antecedent FC. METHODS: We prospectively inquired about FC and their
      characteristics in all patients presenting to an epilepsy clinic through a
      patient questionnaire and interview. We studied the incidence of antecedent
      childhood febrile convulsions in relation to epilepsy diagnosis. RESULTS: FC were
      reported by 133 of 1005 study patients (13.2%). TLE was more likely to be
      preceded by FC (78/310, 25.2%) than extratemporal epilepsy (ETE) (12/216, 5.6%)
      (p < 0.000001) or generalized epilepsy (GE) (16/146, 11.0%) (p < 0.001). Patients
      with GE were more likely than patients with TLE to have had simple FC (p <
      0.00005). Prolonged duration was the most common FC complex feature in TLE
      patients. CONCLUSIONS: We demonstrated a preferential association of FC with
      temporal lobe foci and a weaker association between FC and GE. FC does not appear
      to be a clear risk factor for ETE.

PMID- 9566373
TI  - A potential mechanism of slowed pubertal maturation after chronic administration
      of sodium valproic acid.
AB  - Sodium valproic acid (VPA) occasionally delays pubertal maturation in children
      and gonadal and skeletal growth in juvenile, seizure-prone, inbred DBA/2J mice.
      Fourteen-day-old mice received either VPA or control solution, and the medial
      preoptic area (mPOA) of the hypothalamus was studied after 4, 7, 10, 14, or 18
      days by immunocytochemically processing for gonadotropin-releasing hormone
      (GnRH). Significant differences were found for the proportion of bipolar to
      unipolar neurons in the mPOA. VPA may slow pubertal maturation by altering
      neurochemical systems that normally play an important role in timing maturation
      of the GnRH pulse generator.

PMID- 9566375
TI  - Cortical myoclonus: sensorimotor hyperexcitability.
AB  - Cortical or cortical reflex myoclonus is characterized by abnormally enlarged
      cortical somatosensory evoked potentials (giant SEPs), which most likely reflect
      pathologically hyperexcitable sensorimotor cortex. To clarify the pathogenesis of
      myoclonus of cortical origin, we simultaneously recorded SEPs and whole head
      somatosensory evoked magnetic fields (SEFs) following electric stimulation of the
      median nerve at the wrist in six patients with cortical myoclonus. N20m and
      enlarged P30m were observed in all patients and were localized at the posterior
      bank of the central sulcus (Brodmann area 3b of the primary somatosensory
      cortex). In addition, P25m and N35m components of SEFs were recognized in five
      and four patients, respectively. P25m component, that is, the magnetic
      counterpart of P25 in EEG, was the earliest cortical component showing
      enhancement in patients. Multidipole analysis combined with magnetic resonance
      imaging (MRI) coregistration revealed that the generators of P25m were in the
      precentral gyrus in four patients and in the postcentral gyrus in one patient.
      The second SEFs around 200 msec after the single stimulus were recorded in three
      patients at area 3b (repetitive SEFs); two of whom showed negative as well as
      positive myoclonus. The importance of motor cortex for the generation of cortical
      reflex myoclonus was thus demonstrated. The pathologic features of SEFs suggest
      abnormal excitability of primary sensorimotor cortex.

PMID- 9566374
TI  - Functional MRI lateralization of memory in temporal lobe epilepsy.
AB  - OBJECTIVE: To determine the feasibility of using functional magnetic resonance
      imaging (fMRI) to detect asymmetries in the lateralization of memory activation
      in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial
      temporal lobe function is a critical aspect of the preoperative evaluation for
      epilepsy surgery, both for predicting postoperative memory deficits and for
      seizure lateralization. fMRI offers several potential advantages over the current
      gold standard, intracarotid amobarbital testing (IAT). fMRI has already been
      successfully applied to language lateralization in TLE. METHODS: fMRI was carried
      out in eight normal subjects and 10 consecutively recruited patients with TLE
      undergoing preoperative evaluation for epilepsy surgery. A complex visual scene
      encoding task known to activate mesial temporal structures was used during fMRI.
      Asymmetry ratios for mesial temporal activation were calculated, using regions of
      interest defined in normals. Patient findings were compared with the results of
      IAT performed as part of routine clinical evaluation. RESULTS: Task activation
      was nearly symmetric in normal subjects, whereas in patients with TLE,
      significant asymmetries were observed. In all nine patients in whom the IAT
      result was interpretable, memory asymmetry by fMRI concurred with the findings of
      IAT including two patients with paradoxical IAT memory lateralization ipsilateral
      to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory
      activation in patients with TLE. Because fMRI studies are noninvasive and provide
      excellent spatial resolution for functional activation, these preliminary results
      suggest a promising role for fMRI in improving the preoperative evaluation for
      epilepsy surgery.

PMID- 9566376
TI  - Regional cerebral blood flow and language dominance: SPECT during intracarotid
      amobarbital testing.
AB  - We examined the relation between language dominance and regional cerebral blood
      flow (rCBF) during the intracarotid amobarbital procedure (IAP). A previous
      report limited to three patients suggested that dominant rather than nondominant
      hemisphere IAP may have a differential effect on rCBF. Behavioral assessment
      during the IAP also suggests that dominant hemisphere injection results in a
      differential effect on memory and affective symptoms rather than nondominant
      injection. Thirteen patients were assessed using single-photon emission CT
      (SPECT) brain imaging during both left and right IAP. The SPECTs were
      coregistered with the individual's MRI. Changes in rCBF during each IAP were
      compared with the patient's baseline SPECT. Nine patients had left hemisphere
      dominance, two were right dominant, and two had bilateral speech representation.
      In the left dominant subjects, left-hemisphere injection had a consistently
      greater effect on rCBF than right-hemisphere injection in the anterior (p <
      0.005) and posterior (p < 0.01) temporal neocortex. There was also a trend for
      greater hypoperfusion in the frontal lobe of the left hemisphere. rCBF in the
      ipsilateral hippocampus was not significantly different after each injection (p >
      0.05). In the two patients with right hemisphere speech, the reverse pattern was
      seen, with greater hypoperfusion after right (dominant) hemisphere injection.
      There was no consistent asymmetry in the two patients with bilateral speech.
      Dominant hemisphere IAP results in significantly greater hypoperfusion than does
      nondominant injection. These data provide a physiologic basis for behavioral
      differences noted after dominant versus nondominant IAP.

PMID- 9566377
TI  - Neurologic disease among women with breast implants.
AB  - OBJECTIVE: To investigate the risk of neurologic disease among women with
      silicone breast implants. BACKGROUND: Since 1992, several case series reported an
      association between silicone breast implants and neurologic diseases. METHODS:
      Between 1977 and 1992, 1,135 women received cosmetic silicone breast implants,
      and 7,071 women had breast reduction surgery, as identified by the Danish
      National Register of Patients (NRP). NRP files provided information on numbers
      and types of subsequent neurologic disorders at hospital discharge, which were
      compared with expected numbers, calculated on the basis of national hospital
      discharge rates. RESULTS: In the two study cohorts, hospital discharge rates for
      neurologic diseases were raised by some 60% to 70% compared with Danish women in
      general. Among women with silicone breast implants, 13 subsequently developed a
      neurologic disorder compared with 7.7 expected; whereas in the comparison group,
      63 observed versus 39.1 expected disorders were recorded. These results indicate
      that relative to the comparison cohort, women with implants had no excessive
      levels of definite neurologic disease. Furthermore, medical record reviews
      revealed that the majority of women with implants discharged with a neurologic
      diagnosis had either symptoms before implant surgery or neurologic symptoms
      secondary to degenerative diseases. CONCLUSIONS: Our findings do not support the
      hypothesis of silicone-induced neurologic disease. The reasons for the elevated
      rates of neurologic disease in both the exposed and comparison cohorts remain
      unclear, but may reflect selection processes associated with these women seeking
      medical care more often than the general population.

PMID- 9566378
TI  - Breast implants and risk of neurologic disease: a population-based cohort study
      in Sweden.
AB  - OBJECTIVE: To examine the risk of neurologic disorders among women with breast
      implants. BACKGROUND: Case reports in the literature have raised concern about a
      possible link between silicone breast implants and some types of neurologic
      disorders, but there is a dearth of epidemiologic studies in this area. METHODS:
      Through the nationwide Swedish hospital discharge register, we identified a
      population-based cohort of 7433 women with breast implants. A similarly
      identified cohort of 3351 women who underwent breast reduction surgery served as
      a comparison. The women were followed from 1972 (or date of breast surgery if it
      occurred later) through 1993 by means of record linkages and review of inpatient
      medical records. Ratios of observed to expected numbers, and relative risks (RR)
      with 95% confidence intervals (CI), were calculated as measures of the risk of
      neurologic diseases among women with implants. RESULTS: A direct comparison of
      the exposed (implant) versus comparison (breast reduction) groups, after
      exclusion of patients with pre-existing disease or incorrect neurologic
      diagnoses, showed no excess risk among implant patients (RR = 0.8; 95% CI = 0.5
      to 1.4). When external rates derived from the background population were used as
      comparison, we found a small, statistically nonsignificant excess of neurologic
      disorders both in the breast implant (RR = 1.3; 95% CI = 0.9 to 1.9) and the
      breast reduction (RR = 1.5; 95% CI = 0.9 to 2.4) cohorts. CONCLUSION: Our results
      provide no support for the conjecture that breast implants cause neurologic
      disease.

PMID- 9566379
TI  - Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid
      angiopathy.
AB  - OBJECTIVE: Hemorrhage related to cerebral amyloid angiopathy (CAA) appears to
      occur through a multistep pathway that includes deposition of beta-amyloid in
      cerebral vessels and specific vasculopathic changes in the amyloid-laden vessels,
      such as cracking of the vessel wall. Recent reports suggest a positive
      association between CAA-related hemorrhage and both the apolipoprotein E (APOE)
      epsilon4 allele and, unexpectedly, the APOE epsilon2 allele. Unlike APOE
      epsilon4, APOE epsilon2 does not appear to act through increased beta-amyloid
      deposition. We therefore sought to determine whether it might specifically
      accelerate the second step in this pathway, that is, development of the
      vasculopathic changes that lead to hemorrhage. METHODS: To determine the role of
      APOE in development of vasculopathic changes, we compared APOE genotypes in two
      groups of postmortem brains: 52 brains with complete amyloid replacement of
      vessel walls but without vasculopathic changes, and 23 brains with complete
      amyloid replacement of vessels with the accompanying changes of cracking of the
      vessel wall and paravascular leaking of blood. RESULTS: Frequency of APOE
      epsilon2 was significantly greater in the group with vasculopathy (0.09) than the
      group without (0.01, p = 0.03). The groups did not differ in mean age or extent
      of neuritic plaques. Analysis of a clinical series of patients with CAA-related
      hemorrhage confirmed an overrepresentation of APOE epsilon2 as well as an
      association between this allele and earlier age of first hemorrhage. CONCLUSIONS:
      These data suggest that APOE epsilon2 and epsilon4 might promote CAA-related
      hemorrhage through separate mechanisms: epsilon4 by enhancing amyloid deposition
      and epsilon2 by causing amyloid-laden vessels to undergo the vasculopathic
      changes that lead to rupture.

PMID- 9566380
TI  - A population study on blood-brain barrier function in 85-year-olds: relation to
      Alzheimer's disease and vascular dementia.
AB  - We investigated blood-brain barrier (BBB) function in relation to Alzheimer's
      disease (AD) and vascular dementia (VAD) in the very elderly. Sixty-five 85-year
      old persons from a population-based sample were followed for 3 years; 29 were
      demented at age 85 (13 with AD, 14 with VAD, and 2 with other dementias), 7
      developed dementia during follow-up, and 29 remained nondemented. CSF/serum
      albumin ratio was used as as a measure of BBB function. Dementia was defined
      according to the DSM-III-R, AD according to the NINCDS-ADRDA criteria, and VAD
      according to the NINDS-Association Internationale pour la Recherche et
      l'Enseignement en Neurosciences (AIREN) criteria. Mean CSF/serum albumin ratio
      was higher in all dementias (8.5 +/- 4.3; p = 0.007) and in the subtypes AD (8.9
      +/- 5.3; p = 0.046) and VAD (8.7 +/- 3.5; p = 0.002) than in nondemented
      individuals (versus 6.5 +/- 2.0), but it was not related to dementia severity.
      Nondemented women at age 85 (n = 3) who developed dementia during the follow-up
      had a higher CSF/serum albumin ratio than those not developing dementia (10.4 +/-
      2.0 versus 6.0 +/- 1.9; p = 0.007). Nondemented individuals lacking the
      apolipoprotein E epsilon3 allele (n = 4) had a higher CSF/serum albumin ratio
      (9.3 +/- 0.8 versus 6.6 +/- 2.1; p = 0.029) than other individuals. A relative
      BBB dysfunction is associated with both AD and VAD among very elderly
      individuals. This finding is possibly found early in the disease before the onset
      of clinical dementia.

PMID- 9566381
TI  - White matter changes with normal aging.
AB  - We evaluated brain tissue compartments in 72 healthy volunteers between the ages
      of 18 and 81 years with quantitative MRI. The intracranial fraction of white
      matter was significantly lower in the age categories above 59 years. The CSF
      fraction increased significantly with age, consistent with previous reports. The
      intracranial percentage of gray matter decreased somewhat with age, but there was
      no significant difference between the youngest subjects and the subjects above
      59. A covariance adjustment for the volume of hyperintensities did not alter the
      foregoing results. The intracranial percentage of white matter volume was
      strongly correlated with the percentage volume of CSF. The finding of a highly
      significant decrease with age in white matter, in the absence of a substantial
      decrease in gray matter, is consistent with recent neuropathologic reports in
      humans and nonhuman primates.

PMID- 9566383
TI  - Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging.
AB  - Anti-inflammatory drugs have been suggested as a possible treatment for
      Alzheimer's disease (AD). The association of immune proteins and immune-competent
      microglial cells with senile plaques (SP) in both AD and normal aging suggests
      that these drugs may be able to modify the course of AD, either by interfering
      with SP formation or by suppressing the inflammation associated with SP. We
      compared postmortem brain tissue from elderly, nondemented, arthritic patients
      with a history of chronic nonsteroidal anti-inflammatory drug (NSAID) use (n =
      32, aged 77 +/- 7 years) and nondemented control subjects with no history of
      arthritis or other condition that might promote the regular use of NSAIDs (n =
      34, aged 77 +/- 6 years). In both the NSAID-treated group and control subjects,
      59% of patients had some SP. There was no difference between the two groups in
      the mean number of plaques or in the number of specific SP subtypes (diffuse or
      neuritic). The degree of neurofibrillary pathology was also similar. Activated
      microglia were identified using CR3/43, an anti-MHC class II antibody. Both
      patient age and the presence of SP correlated positively with the number of
      CR3/43+ microglia (p < 0.02), whereas NSAID use was associated with less
      microglial activation (p < 0.01). Control patients with SP had almost three times
      the number of activated microglia as NSAID-treated patients with SP (11 versus 4
      cells/mm2, p < 0.02). These results suggest that if NSAID use is effective in
      treating AD, the mechanism is more likely to be through the suppression of
      microglial activity than by inhibiting the formation of SP or neurofibrillary
      tangles.

PMID- 9566382
TI  - Relating anatomy to function in Alzheimer's disease: neuropsychological profiles
      predict regional neuropathology 5 years later.
AB  - Neuropsychological profiles were assessed in a large group of nondemented control
      subjects (n = 261) and individuals with dementia of the Alzheimer type (DAT) (n =
      407) by subjecting their psychometric test results to a factor analysis.
      Nondemented control subjects were functionally homogeneous with only one factor
      accounting for the results. The results of the factor analysis on the very mild
      DAT and mild DAT groups, however, yielded a mental control/frontal factor, a
      memory-verbal/temporal factor, and a visuospatial/parietal factor. Forty-one of
      the original set of participants came to autopsy an average of 5.1 years after
      psychometric testing and had neurofibrillary tangles, total senile plaques, and
      cored senile plaques estimated from frontal, temporal, and parietal regions. The
      results of correlations indicated that the relative burden of cored senile
      plaques was systematically related to the three psychometric factors. These
      results suggest a connection between the specific functions as defined by
      neuropsychological measures and specific neuropathology occurring in associated
      areas of cortex.

PMID- 9566384
TI  - Earlier onset of Alzheimer's disease in men with Down syndrome.
AB  - BACKGROUND: Virtually all individuals with Down syndrome (DS) have
      neuropathologic changes characteristic of Alzheimer's disease (AD) beginning at
      40 years of age. Few studies have examined factors that influence age at onset of
      AD in DS. We investigated whether sex differences in age at onset and risk of AD
      among adults with DS are similar to those observed in the general population and
      whether the effect of sex on risk of AD is modified by apolipoprotein E (APOE)
      genotype. METHODS: A community-based sample of 111 adults with cytogenetically
      confirmed DS (34 to 71 years of age) was ascertained through the New York State
      Developmental Disabilities system. A semistructured interview with caregivers and
      review of medical records was used to ascertain the presence or absence of AD.
      APOE genotyping was carried out without knowledge of the subject's medical
      history or clinical diagnosis. RESULTS AND CONCLUSIONS: Both male gender and the
      presence of an APOE epsilon4 allele were associated with an earlier onset of AD.
      Compared with women, men with DS were three times as likely to develop AD.
      Compared with those with the APOE 3/3 genotype, adults with DS with the 3/4 or
      4/4 genotypes were four times as likely to develop AD. No individual with an APOE
      epsilon2 allele developed AD. No evidence of interaction of sex and APOE genotype
      was found in risk of AD. The higher risk of AD in men may be related to
      differences in hormonal function between men and women with DS that are distinct
      from those in the general population.

PMID- 9566385
TI  - Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal
      Study on Aging.
AB  - OBJECTIVE: To study the association of estrogen-replacement therapy and other
      estrogen-related variables with Alzheimer's disease in postmenopausal women.
      BACKGROUND: Postmenopausal estrogen use has been reported to lower the risk of
      Alzheimer's disease. DESIGN: A population-based, multicenter survey was carried
      out in eight Italian municipalities. The sample of 2,816 women, aged 65 to 84
      years, was randomly selected from the population register of each municipality
      and stratified in 5-year age groups. All women were screened using the Mini
      Mental State Examination and interviewed concerning risk factors. Those who
      screened positive underwent a clinical assessment. Dementia syndrome was
      diagnosed according to DSM-III-R criteria, and Alzheimer's disease was diagnosed
      according to NINCDS-ADRDA criteria for possible and probable Alzheimer's disease.
      RESULTS: The estimated prevalence of postmenopausal estrogen use adjusted to the
      1991 Italian female population was 12.3%. The frequency of estrogen use was
      higher among nonpatients compared with Alzheimer's disease patients (odds ratio,
      0.24; 95% confidence interval, 0.07 to 0.77). The inverse association between
      estrogen therapy and Alzheimer's disease remained significant after adjustment
      for age, education, age at menarche, age at menopause, smoking and alcohol
      habits, body weight at the age of 50 years, and number of children (odds ratio,
      0.28; 95% confidence interval, 0.08 to 0.98). CONCLUSIONS: Our data from a
      population-based study support the hypothesis that estrogen-replacement therapy
      is associated with a reduced prevalence of Alzheimer's disease in postmenopausal
      women. Prospective clinical trials are required to enable women and their
      physicians to weigh risks and benefits of estrogen-replacement therapy for the
      prevention of dementia.

PMID- 9566386
TI  - Prevalence of dementia in Chinese elderly in Hong Kong.
AB  - This study examines the prevalence of dementia in elderly Chinese aged 70 years
      and older in Hong Kong using a two-phase design. In phase 1, 1,034 elderly were
      interviewed with the Cantonese version of the Mini-Mental State Examination.
      Those who scored below the cutoff points and a subsample of those with scores in
      the normal range were interviewed in phase 2 to identify those with dementia. The
      overall weighted prevalence of dementia in our subjects was 6.1 +/- 0.7%, which
      is at the lower end of the range of rates reported in whites. Alzheimer's disease
      (AD) accounted for 64.6% and vascular dementia, 29.3%. Our results, together with
      previous studies in Chinese populations, suggest that the rates of AD in Chinese
      are low compared with those in whites. Substantial differences are possible in
      the epidemiology of dementia across cultures related to interactions of genetic
      and environmental factors.

PMID- 9566387
TI  - Tactile salience influences extinction.
AB  - We delivered unilateral (left or right) or bilateral tactile stimuli to hands or
      feet of right-brain-damaged patients, six with tactile extinction and two
      without. Stimuli were simple touches or sliding stimuli directed proximo-distally
      (e.g., toward the fingers) or disto-proximally (e.g., toward the forearm).
      Patients were asked to report number (one or two), type (touch or slide), and
      direction (proximo-distally or disto-proximally) of the experimental stimuli.
      Nonextinction patients performed perfectly. Extinction patients, although
      accurate in reporting single stimuli, omitted left stimuli under double-stimuli
      conditions. However, the number of left stimuli detected consciously was related
      to an imbalance of the salience between left and right stimuli. Moreover, in
      three patients the extinguished, left-sided stimulus, even when inaccessible to
      consciousness, influenced implicitly the report of the features of the right
      stimulus. Thus, the relationships between left and right stimuli can modulate
      both overtly and covertly the performance of extinction patients.

PMID- 9566388
TI  - Gender-related penetrance and de novo GTP-cyclohydrolase I gene mutations in dopa
      responsive dystonia.
AB  - We evaluated the influence of gender on penetrance of GTP-cyclohydrolase I (GCH)
      gene mutations in hereditary progressive dystonia/dopa-responsive dystonia
      (HPD/DRD) and determined whether some apparently sporadic HPD/DRD patients owe
      their disorder to a de novo mutation of the GCH gene. Previous clinical
      investigations of HPD/DRD have shown a predominance of affected women, with
      approximately half of HPD/DRD patients being sporadic. We conducted genomic DNA
      sequencing of the GCH gene in five HPD/DRD families having at least two
      generations of affected members and in four apparently sporadic cases and all of
      their parents. In the nine HPD/DRD pedigrees, we found independent mutations of
      the GCH gene (five deletions, one insertion, one nonsense mutation, and two point
      mutations at splice acceptor sites). The female-to-male ratio of the HPD/DRD
      patients was 4.3 with the penetrance of GCH gene mutations in women being 2.3
      times higher than that in men (87% versus 38%, p = 0.026). There was no
      significant difference in the penetrance between maternally and paternally
      transmitted offspring. All of the four sporadic cases had de novo mutations
      because none of their parents were carriers. The results demonstrate gender
      related incomplete penetrance of GCH gene mutations in HPD/DRD and suggest that
      this may not be due to genomic imprinting. Our data also suggest a relatively
      high spontaneous mutation rate of the GCH gene in this autosomal dominant
      disorder.

PMID- 9566389
TI  - Reduced lymphoblast neopterin detects GTP cyclohydrolase dysfunction in dopa
      responsive dystonia.
AB  - OBJECTIVE: To demonstrate that measurement of endogenous neopterin levels in
      unstimulated lymphoblasts identifies inherited GTP cyclohydrolase 1 (GCH1)
      dysfunction and can be a diagnostic test for dopa-responsive dystonia (DRD).
      BACKGROUND: DRD results from decreased dopamine biosynthesis due to dysfunctional
      GCH1. GCH1 is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin
      (BH4), an essential cofactor for catecholamine synthesis. Mutations in the GCH1
      coding region are identified in 60 to 70% of DRD cases; in others, the cause of
      GCH1 dysfunction is unknown. METHODS: Using HPLC, we measured endogenous
      neopterin, the main byproduct of the GCH1 reaction, in lymphoblasts under basal
      conditions and following GCH1 stimulation conditions. RESULTS: In a four
      generation family, all identified carriers of dysfunctional GCH1 had basal
      neopterin levels that were below those of controls. The spouse of one carrier had
      a mutation in exon 6 of GCH1. Although this man's GCH1 function appeared
      unaffected by this, his daughter, who was a compound heterozygote with her
      mother's dysfunctional GCH1 and this mutation, had a phenotype that was more
      severe than that of typical DRD. Cytokine or phytohemagglutinin (PHA) did not
      induce GCH1 activity in any carrier of dysfunctional GCH1; controls who did not
      respond to PHA had increased neopterin levels following cytokine induction.
      CONCLUSIONS: Endogenous neopterin measurement in unstimulated lymphoblasts is an
      accurate tool to identify dysfunctional GCH1 and a potential specific diagnostic
      marker for dysfunctional GCH1 in DRD and other neurologic disorders. Not all
      mutations in GCH1 affect GCH1 enzyme activity. PHA induction alone, previously
      used by others, may result in incorrect identification of GCH1 dysfunction in
      DRD.

PMID- 9566390
TI  - Striatal D2 receptors in symptomatic and asymptomatic carriers of dopa-responsive
      dystonia measured with [11C]-raclopride and positron-emission tomography.
AB  - We tested the hypothesis that asymptomatic carriers of dopa-responsive dystonia
      (DRD) have increased dopamine D2 receptors in the striatum that protect them from
      the clinical manifestations of dopaminergic deficiency. We examined striatal D2
      receptor binding in (1) symptomatic subjects (treated and untreated) and (2)
      asymptomatic gene carriers. Using [11C]-raclopride PET, we found elevated
      striatal D2-receptor binding in both groups. In one of our drug-naive symptomatic
      subjects, 7 months of treatment with levodopa/carbidopa did not affect the
      receptor binding as measured on a second scan. We conclude that increased D2
      receptor binding in DRD may be a homeostatic response to the dopaminergic deficit
      in subjects carrying the DRD gene, but is not the sole factor determining the
      clinical state of these individuals.

PMID- 9566391
TI  - Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of
      Huntington's and Parkinson's diseases.
AB  - OBJECTIVE: To determine cerebral energy status in patients with Huntington's
      disease (HD) and Parkinson's disease (PD). METHODS: The study included 15
      patients with DNA-proven, symptomatic HD and five patients with medically
      treated, idiopathic PD, all of whom were candidates for neurotransplant
      treatment, as well as 20 age-related normal subjects. Quantitative noninvasive,
      MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia
      (BG), occipital gray matter, and posterior parietal white matter; in addition,
      quantitative phosphorus and proton-decoupled phosphorus MRS of superior
      biparietal white and gray matter was done. Outcome measures were quantitative
      metabolite ratios and millimolar concentrations of neuronal and glial markers,
      creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. RESULTS: In
      volume-corrected control BG (10.46 +/- 0.37 mM), [Cr] was 29% (p < 0.05) higher
      than in control gray matter (8.10 +/- 1.04 mM). In HD and PD, energy metabolism
      was not abnormal in the four cerebral locations measured by MRS. No increase in
      cerebral lactate or decrease in phosphocreatine and ATP was detected. Small,
      systematic abnormalities in N-acetylaspartate (NAA, decreased), Cr (decreased),
      choline-containing compounds (Cho, increased), and myoinositol (mI, increased)
      were demonstrable in all patient's individually and in summed spectra but were
      insufficient to make diagnosis possible in the individual patient. CONCLUSION:
      Previously described failure of global energy metabolism in HD was not confirmed.
      However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are
      sensitive to +/-10% alterations in key cerebral metabolites, and may be of value
      in noninvasive monitoring of appropriate therapies.

PMID- 9566392
TI  - Neuropathy in diffuse infiltrative lymphocytosis syndrome: an HIV neuropathy, not
      a lymphoma.
AB  - OBJECTIVE: To determine whether CD8 lymphoid infiltrates in nerves of patients
      with HIV-associated diffuse infiltrative lymphocytosis syndrome (DILS)
      corresponds to a lymphomatous neoplastic process or to a proliferation of T cells
      reactional to HIV. BACKGROUND: DILS is characterized by persistent CD8
      hyperlymphocytosis and multivisceral CD8 T-cell infiltration, which may affect
      peripheral nerves. METHODS: Presence of monoclonal T cells and HIV-1 proviral
      load were evaluated by polymerase chain reaction (PCR) techniques in frozen
      peripheral nerve samples from six patients with DILS neuropathy and 22 patients
      with other HIV-associated peripheral neuropathies, including mononeuritis
      multiplex (MM:6), inflammatory demyelinating polyneuropathies (IDP:6), distal
      sensory polyneuropathy (DSP:5), and toxic distal sensory polyneuropathy (TDSP:5).
      RESULTS: Five of six patients with DILS showed no detectable monoclonal T-cell
      clones in their nerves. Nerve proviral load in DILS (6.8 +/- 0.2 log/10(5) cells)
      was much higher than in MM (p < 0.008), IDP (p < 0.001), DSP (p < 0.001), and
      TDSP (p < 0.005). CONCLUSIONS: DILS neuropathy represents a separate entity among
      HIV-associated neuropathies. It is associated with massive HIV proviral load in
      nerve and must not be confused with a peripheral nerve T-cell lymphoma.

PMID- 9566393
TI  - T-cell recognition of muscle acetylcholine receptor subunits in generalized and
      ocular myasthenia gravis.
AB  - OBJECTIVES: Our purpose was to identify the muscle acetylcholine receptor (AChR)
      subunits recognized by autoimmune CD4+ T cells in myasthenia gravis (MG) and
      determine whether they differ in generalized (gMG) and ocular MG (oMG), and as
      gMG progresses. METHODS: We tested the proliferative response of blood CD4+ cells
      from 25 patients with gMG and four patients with oMG to synthetic peptides
      spanning the sequence of each subunit of human muscle AChR. We also investigated
      the antisubunit response of Th1 cells (a CD4+ subset frequently involved in
      autoimmune phenomena) using an enzyme-linked immunospot (ELISPOT) assay of
      antigen-induced secretion of interferon-gamma by individual CD4 cells. RESULTS:
      In gMG patients both the total CD4+ population and the Th1 subset recognized all
      AChR subunits to comparable extents. oMG patients recognized the AChR epsilon
      subunit minimally, and other subunits consistently and more strongly. gMG
      patients whose disease had lasted less than 5 years had lower antisubunit
      responses, and several of them did not recognize some AChR subunits; patients
      whose disease had lasted for 5 or more years had higher antisubunit responses and
      always responded to all AChR subunits. CONCLUSIONS: CD4+ and Thl responses in MG
      involve the entire AChR molecule. This likely results from spreading of the CD4+
      sensitization to increasingly larger parts of the AChR as the disease progresses.
      The differential recognition of AChR subunits in oMG might be related to the
      preferential involvement of extrinsic ocular muscles, which express AChR
      containing the gamma subunit.

PMID- 9566394
TI  - Effects of aerobic training in patients with mitochondrial myopathies.
AB  - We studied the physiologic adaptation of patients with mitochondrial myopathies
      to aerobic training. Ten patients underwent individually supervised, moderate
      intensity aerobic training on a treadmill for 8 weeks. Biochemical and functional
      measures improved with training. Estimated aerobic capacity increased by 30%.
      Blood lactate concentrations at rest and after exercise decreased by 30%. Muscle
      phosphorus magnetic resonance spectroscopy measurements of adenosine diphosphate
      recovery after exercise improved by more than 60%. Fatigue and tolerance to daily
      activities also improved. Although the improvement in exercise tolerance may be
      due in part to reversal of the effects of secondary deconditioning, this
      uncontrolled clinical trial suggests that aerobic training can benefit patients
      with mitochondrial myopathies.

PMID- 9566395
TI  - Charcot-Marie-Tooth disease type 1A with 17p duplication in infancy and early
      childhood: a longitudinal clinical and electrophysiologic study.
AB  - OBJECTIVE: We describe longitudinal clinical and electrophysiologic evaluation of
      Charcot-Marie-Tooth disease type 1A (CMT-1A) in infancy and early childhood.
      BACKGROUND: The clinical picture and electrophysiologic evaluation of CMT-1A
      during the age of nerve conduction maturation have not been documented.
      DESIGN/METHODS: Twenty at-risk children from six unrelated CMT-1A families were
      examined in the first 5 years of life. Initial ages were 1 month to 4 years
      (mean, 1.5 years) and final ages 4 to 19 years (mean, 9 years). All subjects had
      two or more motor and sensory conduction velocities (MCV and SCV), corrected
      distal motor latencies (DML), and F-waves. RESULTS: Twelve children were
      affected. Initially, two of these (17%) had symptoms, whereas five (42%) were
      symptomatic at the end. Numbers of abnormal examinations at the beginning was six
      (50%) and at conclusion was 10 (83%). None of the patients were disabled. From 2
      years of age, all affected children had abnormal MCV, SVC, F-waves, and DML.
      Prolonged DML was already present in the first months of life and preceded
      slowing of MCV in three cases. CONCLUSION: The electrophysiologic studies were
      concordant with the presence or absence of the CMT-1A DNA duplication. In most
      CMT-1A patients, symptoms appear in early childhood, although the florid clinical
      picture does not occur until the second decade of life. Serial electrophysiologic
      studies can detect the CMT-1A gene carrier in infancy.

PMID- 9566396
TI  - Charcot-Marie-Tooth disease and Noonan syndrome with giant proximal nerve
      hypertrophy.
AB  - We report a family with Noonan syndrome (NS), giant proximal nerve hypertrophy,
      and hereditary motor sensory neuropathy type 1A (HMSN1A). Five members of a
      family were found to have clinical features of NS. In all cases, NS was
      associated with giant hypertrophy of proximal nerves and two individuals also
      exhibited cafe-au-lait spots. In one case, an 8-to-10-cm diameter pelvic mass was
      shown to be a grossly hypertrophied nerve, with histologic features of
      demyelination and remyelination. In addition, four of five family members
      affected with NS were found to have HMSN1A clinically and by demonstration of
      constitutional HMSN1A duplication on DNA testing. Linkage analysis for NS ruled
      out the involvement of the neurofibromatosis type 1 gene and the known NS locus
      in chromosome 12, supporting the existence of an additional NS locus.

PMID- 9566397
TI  - X-linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and
      electrophysiologic study.
AB  - OBJECTIVE: To relate X-linked Charcot-Marie-Tooth disease (CMTX) phenotypes to
      gender and type of neuropathy by the study of a large series of CMTX patients
      with proven Cx32 point mutations. BACKGROUND: CMTX is an X-linked form of Charcot
      Marie-Tooth disease, caused by mutations in the connexin 32 gene. Males are
      usually more severely affected and have slower nerve conduction velocities than
      females. METHODS: Forty-eight patients from 10 families with Cx32 mutations were
      examined clinically and electrophysiologically. Mutations were characterized in
      index cases by automatic sequencing and detected in at-risk individuals by
      polymerase chain reaction (PCR)-restriction or single strand conformation
      polymorphism (SSCP) analysis. Two patients from different families had light and
      electron microscopy examination of a sural nerve biopsy. RESULTS: Males (n = 21)
      were more severely affected than females (n = 27), although six of the females
      were severely disabled. In the majority of males, the median motor nerve
      conduction velocity (MNCV) was between 30 and 40 m/s, whereas in females it
      ranged from 30 to normal values. Two children with mutation, a 6-year-old boy and
      a 7-year-old girl, were normal clinically and electrophysiologically. In most
      patients, the amplitude of motor nerve compound muscle action potentials (CMAP)
      was reduced in all nerves tested. MNCV was reduced as a function of the degree of
      axonal loss. A significant correlation was found between the decrease in CMAP
      amplitude and MNCV in the median, ulnar, and peroneal nerves. Sural nerve
      biopsies in one patient with a missense and one with a nonsense mutation both
      showed axonal neuropathy. CONCLUSION: Electrophysiologic and histologic findings
      support primary axonal neuropathy in CMTX with Cx32 mutations. Clinical and
      electrophysiologic data in males with different missense mutations in the of Cx32
      gene differed significantly. Furthermore, males with a nonsense mutation
      (Arg22Stop) had earlier onset and a more severe phenotype than males with
      missense mutations.

PMID- 9566398
TI  - Decay of postexercise augmentation in the Lambert-Eaton myasthenic syndrome:
      effect of cooling.
AB  - The effect of local cooling on surface recorded compound muscle action potential
      (CMAP) amplitude was studied in five patients with the Lambert-Eaton myasthenic
      syndrome (LEMS). The time course of decay of postexercise augmentation of CMAP
      amplitude characteristically seen in patients with LEMS was determined. We
      recorded the CMAP from abductor digiti minimi (ADM) in response to supramaximal
      stimulation of the ulnar nerve. Thirty consecutive stimuli were delivered at 1 Hz
      immediately after a 10-second period of maximal voluntary contraction. Skin
      surface temperature was recorded throughout. Initial testing at approximately 30
      degrees C was repeated after cooling the hand and forearm by 6 to 12 degrees C.
      The effects of blood flow on temperature were counteracted by the application of
      a sphygmomanometer cuff, inflated above systolic blood pressure. The CMAP
      amplitude following contraction decayed in an exponential manner both during warm
      and cold conditions. The mean time constant for decay (1/b) in all patients was
      increased by approximately 25% after cooling. This prolongation of the period of
      postexercise augmentation of CMAP amplitude in LEMS after cooling concurs with
      patient reports of symptomatic improvement in cold weather. The mechanism for
      this benefit is thought to be due to reduction in the rate of removal of calcium
      ions from the nerve terminal following stimulation, similar to that seen in
      animal models of short-term synaptic enhancement.

PMID- 9566399
TI  - Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study.
AB  - Clinical, neuroanatomic, neurobehavioral, and functional brain-imaging studies
      suggest a role for the cerebellum in cognitive functions, including attention.
      However, the cerebellum has not been systematically studied in attention-deficit
      hyperactivity disorder (ADHD). We quantified the cerebellar and vermal volumes,
      and the midsagittal areas of three vermal regions, from MRIs of 46 right-handed
      boys with ADHD and 47 matched healthy controls. Vermal volume was significantly
      less in the boys with ADHD. This reduction involved mainly the posterior inferior
      lobe (lobules VIII to X) but not the posterior superior lobe (lobules VI to VII).
      These results remained significant even after adjustment for brain volume and IQ.
      A cerebello-thalamo-prefrontal circuit dysfunction may subserve the motor
      control, inhibition, and executive function deficits encountered in ADHD.

PMID- 9566400
TI  - Effects of weight loss on the course of idiopathic intracranial hypertension in
      women.
AB  - OBJECTIVE: To determine the role of weight loss in the treatment of idiopathic
      intracranial hypertension (IIH) in obese women. METHODS: Chart review of 250
      patients with suspected IIH revealed 58 women who met our criteria, did not
      undergo early surgical intervention, and had adequate documentation of visual
      status, papilledema, and weight at the baseline evaluation and at 6 months or
      longer. Patients were divided into two groups based on whether weight loss > or =
      2.5 kg occurred during any 3-month interval. Papilledema grade, visual acuity,
      and visual field grade at 6 months or longer and the time to improve each were
      recorded. RESULTS: Mean time in months to improve one grade for papilledema and
      visual field in one eye was 4.0 versus 6.7 (p = 0.013) and 4.6 versus 12.2 (p =
      0.032), respectively, for the 38 patients with weight loss compared with the 20
      patients with no weight loss. Papilledema resolved in 28/38 with weight loss
      (mean, 7.6 months) and 8/20 without weight loss (mean, 10.2 months; p = 0.352).
      There were no differences in final visual acuity or visual field between the two
      groups, but the papilledema grade was slightly better in the worst eye in each
      patient at baseline in the weight loss group (p = 0.03). CONCLUSIONS: Weight
      reduction is associated with more rapid recovery of both papilledema and visual
      field dysfunction in patients with IIH compared with those who do not lose
      weight.

PMID- 9566401
TI  - Idiopathic intracranial hypertension and orthostatic edema may share a common
      pathogenesis.
AB  - Our aim was to determine the frequency of orthostatic edema (OE) in patients with
      idiopathic intracranial hypertension (IIH). We evaluated 30 women with IIH for
      evidence of OE by comparing sodium and water excretion in the recumbent and
      standing postures and morning and evening body weights. Data were compared with
      findings in 30 women with OE, 22 weight-matched obese normal subjects, and 20
      lean normal subjects. The effect of treatment with diuretics or diuretics plus
      sympathomimetic agents was compared. Seventy-seven percent of IIH patients had
      evidence of peripheral edema and 80% had significant orthostatic retention of
      sodium or water. Excretion of a standard saline load and of a tap water load was
      significantly impaired in the upright posture in the IIH and OE patients compared
      with the lean and obese normal subjects. Diuretic therapy induced weight loss (up
      to 9 kg) and decreased mean weight gain from morning to evening in 5 of 12
      patients treated. In seven patients also treated with diuretics plus
      sympathomimetic drugs, the diuretic-induced morning weight loss and morning to
      evening weight gain were both significantly improved with the addition of
      sympathomimetic agents. Therapy reduced the frequency or severity of headaches in
      seven patients and reduced papilledema in four patients who received no other
      concurrent treatment for IIH. The orthostatic retention of sodium and water and
      the consequent edema is very similar in IIH and OE patients, suggesting a common
      pathogenesis for both disorders. Diuretic therapy, dietary salt and water
      restriction, and planned periods of recumbency merit study as a treatment for
      these patients.

PMID- 9566402
TI  - Variable clinical expression of mutations in the P/Q-type calcium channel gene in
      familial hemiplegic migraine. Dutch Migraine Genetics Research Group.
AB  - Familial hemiplegic migraine (FHM) is an autosomal dominant subtype of migraine
      with aura, with half of the families being assigned to chromosome 19p13. We
      identified missense mutations in a brain-specific calcium channel alpha1A-subunit
      (CACNA1A) gene on 19p13 segregating with FHM and truncating mutations in families
      with episodic ataxia type 2 (EA-2). Expansions of an intragenic CAG repeat have
      been shown in autosomal dominant cerebellar ataxia (SCA6). Hence, FHM, EA-2, and
      SCA6 are allelic ion channel disorders. We analyzed the phenotype-genotype
      relation in three unrelated FHM families with the calcium channel alpha1A-subunit
      gene mutations I1811L (two families) and V714A (one family). We found mutations
      in all but three patients with FHM (i.e., three phenocopies). In addition, the
      I1811L mutation occurred in two patients with "nonhemiplegic" migraine and in one
      subject without migraine. Cerebellar ataxia was found in both families with the
      I1811L mutation but not in the family with the V714A mutation. We failed to find
      expansions of the intragenic CAG repeat in FHM patients with cerebellar ataxia.
      We conclude that the I1811L mutation causes both FHM and cerebellar ataxia
      independent of the number of CAG repeats. The I1811L mutation may also occur in
      "normal" migraine patients, supporting the hypothesis that FHM is part of the
      migraine spectrum.

PMID- 9566403
TI  - Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex
      in migraine.
AB  - OBJECTIVES: We hypothesized that the hyperexcitability of occipital cortex
      neurons may predispose migraine subjects to develop spreading depression, the
      putative basis of migraine with aura (MwA). To date there is no direct
      physiologic correlate confirming this in patients. Accordingly, we evaluated the
      differences in the threshold of occipital cortex excitation between MwA patients
      and normal controls (C) using transcranial magnetic stimulation (TMS). METHODS:
      TMS was performed using the Cadwell MES 10 stimulator. A circular coil 9.5 cm in
      diameter was applied to the occipital scalp (7 cm above the inion). Stimulator
      intensity was increased in 10% increments until subjects reported visual
      phenomena or 100% intensity was reached. Stimulation intensity was then fine
      tuned to determine the threshold at which phosphenes were just visualized.
      RESULTS: Eleven MwA patients, mean age 37 +/- 7 years, were compared with 11 C,
      mean age 37.7 +/- 7 years. The difference in the proportion of subjects with
      phosphene generation between MwA patients and C was significant (MwA patients
      100% versus C 27.3%, p = 0.001). The mean threshold level for MwA patients was
      44.2 +/- 8.6 versus 68.7 +/- 3.1 for C (p = 0.0001). All threshold levels for MwA
      patients were lower than the lowest threshold for C; the MwA patient with the
      lowest threshold had an aura after stimulation. CONCLUSIONS: The threshold for
      excitability of occipital cortex is lower in MwA patients compared with C. This
      is a direct neurophysiologic correlate for clinical observations that have
      indicated hyperexcitability of the occipital cortex in migraineurs.

PMID- 9566404
TI  - Cortical sensorimotor reorganization after spinal cord injury: an
      electroencephalographic study.
AB  - The aim of this study was to determine if cortical motor representation and
      generators change after partial or complete paralysis after spinal cord injury
      (SCI). Previously reported evidence for a change in cortical motor function after
      SCI was derived from transcranial magnetic stimulation. These studies inferred a
      reorganization of the cortical motor system. We applied the new technique of high
      resolution EEG to measure changes in cortical motor representation directly. We
      recorded and mapped the motor potential (MP) of the movement-related cortical
      potentials in 12 SCI patients and 11 control subjects. Results were analyzed
      using a distance metric to compare MP locations between patients and control
      subjects. EEG was coregistered with subject-specific MR images and a boundary
      element model created for dipole source analysis (DSA). When compared with normal
      control subjects, seven quadriparetics had posteriorly located MPs with finger
      movements. One paraparetic had a posterior MP with toe movements, but three who
      could not move the toes had normally located MPs on attempts to move. DSA
      confirmed the electrical field map distributions of the MPs. We are reporting a
      reorganization of cortical motor activity to a posterior location after SCI.
      These results suggest an important role of the somatosensory cortex (S1) in the
      recovery process after SCI.

PMID- 9566405
TI  - CSF neurofilament and glial fibrillary acidic protein in normal pressure
      hydrocephalus.
AB  - We examined CSF levels of markers of neuronal degeneration and astrogliosis-the
      light subunit of the neurofilament triplet protein (NFL) and the glial fibrillary
      acidic protein (GFAP)-in 65 patients with normal pressure hydrocephalus (NPH).
      NFL was increased sixfold (864 +/- 1,538 [mean +/- SD] versus 156 +/- 81 ng/L; p
      < or = 0.001) and GFAP twofold (1,116 +/- 1,085 versus 637 +/- 295 ng/L; p < or =
      0.01) in NPH patients compared with neurologically healthy age-matched controls.
      No correlation was found between any particular symptom or sign and GFAP levels
      in CSF. The levels of NFL, on the other hand, were higher in patients with severe
      symptoms compared with those with moderate or no symptoms. Furthermore, there was
      a correlation between a high level of NFL and gait disturbance, incontinence,
      psychometric incapability, and social dysfunction. A high preoperative NFL level
      was associated with favorable outcome after shunt surgery. This indicates that
      NFL is a marker of ongoing and possibly still-reversible axonal damage in NPH.

PMID- 9566406
TI  - Effect of copolymer-1 on serial gadolinium-enhanced MRI in relapsing remitting
      multiple sclerosis.
AB  - We examined the effect of Copolymer-1 (Cop1) on magnetic resonance (MR) imaging
      changes in 10 patients with relapsing-remitting multiple sclerosis (RRMS).
      Monthly gadolinium (Gd)-enhanced MR imaging was performed for 9 to 27 months in
      the pretreatment period followed by 10 to 14 additional months during Cop1
      treatment. MR images were evaluated by two radiologists (F.S. and R.C.P.) masked
      to the scan date. We found a 57% decrease in the frequency of new Gd-enhancing
      lesions and in the mean area/month of new Gd-enhancing lesions in the Cop1
      treatment period compared with the pretreatment period (0.92 versus 2.20 lesions
      per month and 22 mm2 versus 43 mm2 area/month; p = 0.1, Wilcoxon signed rank
      test). Percentage change in lesion load area on T2-weighted images showed a
      decrease in the accumulation of lesion area during treatment, which was
      significant for the patient group with a longer pretreatment period (p = 0.05,
      Friedman test). These results demonstrate a reduction in the number of new Gd
      enhancing lesions and in the lesion load during Cop1 treatment compared with the
      preceding period without therapy and are suggestive of an effect of Cop1 on MR
      abnormalities observed in multiple sclerosis.

PMID- 9566407
TI  - Tardive dyskinesia in dopa-responsive dystonia: a reappraisal of the dopamine
      hypothesis of tardive dyskinesia.
AB  - Dopa-responsive dystonia, an autosomal-dominant disorder caused by mutations in
      the guanosine triphosphate (GTP)-cyclohydrolase I gene, is characterized by
      severe striatal dopamine depletion. Tardive dyskinesia, on the other hand, has
      often been associated with striatal dopamine overactivity. This article reports
      on a 44-year-old man with dopa-responsive dystonia who developed tardive
      dyskinesia on long-term haloperidol therapy. Nigrostriatal dopamine deficiency
      may be necessary for the development of tardive dyskinesia.

PMID- 9566408
TI  - Absence of mutations in the coding region of the alpha-synuclein gene in
      pathologically proven Parkinson's disease.
AB  - A missense mutation of the alpha-synuclein gene has been associated with
      parkinsonism in a large Italian kindred. Recently, alpha-synuclein was also
      identified in Lewy bodies. Using reverse transcribed-polymerase chain reaction
      (RT-PCR) technique, we sequenced the entire coding region of the alpha-synuclein
      gene using brain tissue from 24 pathologically proven Parkinson's disease cases.
      No mutations were found in any of the patients, suggesting that a mutation at the
      coding region of the alpha-synuclein gene is unlikely to be responsible for
      nigrostriatal degeneration in typical sporadic Parkinson's disease.

PMID- 9566409
TI  - Systemic iron metabolism and mortality from Parkinson's disease.
AB  - Six measures of systemic iron metabolism were used to predict mortality among 103
      patients with Parkinson's disease and 353 controls followed in a longitudinal
      study. Adjusting for gender, education, ethnicity, presence of dementia, and
      extrapyramidal signs, transferrin receptor concentration was strongly associated
      with mortality in patients with PD but not controls. This increase in serum
      transferrin receptor concentration before death suggests that the previously
      observed perturbation in iron metabolism continues throughout the disease course.

PMID- 9566410
TI  - Postmenopausal estrogen use and Parkinson's disease with and without dementia.
AB  - We investigated the effects of estrogen replacement therapy (ERT) on the risk of
      development of dementia in 87 women with Parkinson's disease without dementia
      (PDND), 80 women with Parkinson's disease with dementia (PDD), and 989
      nondemented healthy women from the same community. ERT was protective for the
      development of dementia within the setting of PD (OR 0.22, 95% CI 0.05-1.0) and
      when PDD patients were compared with controls (OR 0.24, 95% CI 0.07-0.78), but
      did not affect the risk of PD. The results of the study suggest that a randomized
      clinical trial of ERT may be warranted.

PMID- 9566411
TI  - X-linked female band heterotopia-male lissencephaly syndrome.
AB  - We report a family with band heterotopia in a mother and daughter and
      lissencephaly in a son (X-linked inheritance pattern). Postmortem examination of
      the boy revealed classical lissencephaly and, among other findings, simplified
      and discontinuous inferior olives without inferior olivary heterotopia. The
      absence of inferior olivary heterotopia may distinguish X-linked lissencephaly
      from other conditions with classic lissencephaly such as Miller-Dieker syndrome.

PMID- 9566412
TI  - Gabapentin does not interact with a contraceptive regimen of norethindrone
      acetate and ethinyl estradiol.
AB  - Anticonvulsants that induce hepatic metabolism increase clearance of oral
      contraceptive hormones and thereby cause contraceptive failure. Gabapentin is not
      metabolized in humans and has little liability for causing metabolic-based drug
      drug interactions. In healthy women receiving 2.5 mg norethindrone acetate and 50
      microg ethinyl estradiol daily for three consecutive menstrual cycles, concurrent
      gabapentin administration did not alter the steady-state pharmacokinetics of
      either hormone. Thus, gabapentin is unlikely to cause contraceptive failure.

PMID- 9566413
TI  - In vivo and in vitro immune variables in patients with narcolepsy and HLA-DR2
      matched controls.
AB  - We investigated cytokine levels (interleukin [IL]-1beta, IL-1ra, IL-2, IL-6,
      tumor necrosis factor [TNF]-alpha, TNF-beta) in plasma and secreted by mitogen
      stimulated blood monocytes and lymphocytes; T-cell subsets; and natural killer
      cell activity in patients with narcolepsy and in human leukocyte antigen (HLA)
      DR2 matched controls. The only significant finding was higher IL-6 secretion by
      monocytes of patients than by those of the HLA-DR2-positive controls. In
      conclusion, we found no major abnormalities of T-cell function in patients with
      narcolepsy, but slight alterations of monocyte function deserving further
      investigation.

PMID- 9566414
TI  - Postpartum cerebral angiopathy with intracerebral hemorrhage in a patient
      receiving lisuride.
AB  - Postpartum cerebral angiopathy is a recognized but infrequent complication of
      ergot alkaloid derivatives. We describe a patient who experienced reversible
      cerebral vasoconstriction with intracerebral hemorrhage (ICH) after ingesting
      lisuride in the postpartum period. Lisuride is likely to cause postpartum
      cerebral angiopathy, and ICH must now be considered a possible cerebrovascular
      complication of postpartum cerebral angiopathy. Our observation calls for further
      study to verify these findings.

PMID- 9566415
TI  - Cerebral vasculitis during FK 506 treatment in a liver transplant patient.
AB  - The immunosuppressive agent FK 506 is widely used in liver transplant patients.
      Neurotoxicity is a major complication of its use. We report progressive and
      irreversible neurologic complications occurring in a 39-year-old woman who
      underwent liver transplantation and was treated with FK 506. Neuropathologic
      examination revealed multiple vasculitic lesions. The possibility of an FK 506
      mediated toxic effect on the cerebral vessels is suggested.

PMID- 9566416
TI  - Middle cerebral artery main stem thrombosis in two siblings with familial
      thrombotic thrombocytopenic purpura.
AB  - Idiopathic thrombotic thrombocytopenic purpura (TTP) is frequently complicated by
      microinfarcts in cerebral cortex and subcortical white matter. We describe two
      sisters who suffered massive hemispheric infarction due to thrombosis of the
      middle cerebral artery main stem during exacerbations of TTP. Acute TTP may be
      associated with intraluminal thrombosis of large-diameter arteries in addition to
      arterioles and capillaries.

PMID- 9566417
TI  - Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura:
      report of seven patients and a meta-analysis.
AB  - We present the results of a meta-analysis using clinical data obtained from seven
      of our patients and 24 previously reported patients with idiopathic
      thrombocytopenic purpura complicated by intracranial hemorrhage. Twenty-four had
      an intracerebral hemorrhage (ICH) and seven had a subdural hematoma (SDH). Mean
      age of the patients with ICH was significantly younger than those with SDH. The
      mortality rate of ICH associated with ITP was similar to that of spontaneous ICH.
      All seven patients with SDH improved without sequelae.

PMID- 9566418
TI  - Rapid development of giant fusiform cerebral aneurysms in angiographically normal
      vessels.
AB  - Several reports have mentioned formation of new saccular aneurysms in previously
      normal-appearing vessels, but de novo fusiform aneurysms have not been reported.
      We describe three children who initially presented with giant fusiform aneurysms
      involving the cervical and petrous portions of the internal carotid artery and
      were treated with balloon occlusion. Between 2 and 6 years later, they were found
      to have new giant fusiform aneurysms in the vertebrobasilar system.

PMID- 9566419
TI  - Heritable connective tissue disorders in cervical artery dissections: a
      prospective study.
AB  - We prospectively evaluated 15 consecutive patients with spontaneous cervical
      artery dissections. Three patients (20%) had a heritable connective tissue
      disorder, each with a unique phenotype. None of these patients met the criteria
      of any of the named syndromes, and collagen and fibrillin analyses were normal.
      Heritable connective tissue disorders are common among patients with spontaneous
      cervical artery dissections, but, despite intensive investigations, the type of
      disorder usually cannot be identified. The underlying arteriopathy in cervical
      artery dissections is likely to be heterogeneous.

PMID- 9566420
TI  - Vertical and horizontal meridian sparing in occipital lobe homonymous
      hemianopias.
AB  - We report two patients with unique homonymous hemianopias from occipital lobe
      infarctions. One patient had vertical meridian sparing, and the other displayed
      horizontal meridian sparing. MRI correlation with the visual field defects
      confirmed that the vertical hemianopic meridian was represented along the border
      of the calcarine lips, and the horizontal meridian lies at the base of the
      calcarine banks deep within the calcarine fissure.

PMID- 9566421
TI  - Cytologically negative carcinomatous meningitis: usefulness of CSF biochemical
      markers.
AB  - Eighteen patients (age range, 28 to 62 years; median, 58) with carcinomatous
      meningitis defined clinically (100%) and neuroradiographically (39%) with
      negative CSF cytology were evaluated with CSF biochemical markers. In only four
      patients (22%), CSF biochemical markers corroborated a diagnosis of carcinomatous
      meningitis.

PMID- 9566422
TI  - Novel muscle chloride channel (CLCN1) mutations in myotonia congenita with
      various modes of inheritance including incomplete dominance and penetrance.
AB  - Autosomal-dominant and -recessive myotonia congenita are caused by mutations in
      the skeletal muscle voltage-gated chloride channel gene (CLCN1). We searched for
      mutations in this gene in 20 unrelated families with myotonia congenita. We
      identified 11 different mutations in 10 families. Two of five new mutations
      (Ala313Thr and Ile556Asn) were both autosomal recessive and dominant with either
      reduced penetrance or incomplete dominance. Mutations in the CLCN1 gene do not
      therefore necessarily behave in a classic Mendelian manner.

PMID- 9566423
TI  - Micturitional disturbance in patients with chronic inflammatory demyelinating
      polyneuropathy.
AB  - Eight of 32 patients (25%) with chronic inflammatory demyelinating polyneuropathy
      (CIDP) had micturitional disturbance, which consisted of voiding difficulty (n =
      4), urgency (n = 4), or urgency incontinence (n = 1). Urodynamic studies on four
      symptomatic patients showed disturbed bladder sensation in two, bladder areflexia
      in one, and neurogenic changes of the external sphincter in one, indicative of
      peripheral parasympathetic and somatic nerve dysfunctions. Cystometry also showed
      detrusor overactivity in two patients but no evidence of CNS involvement,
      evidence that bladder overactivity occurs by probable pelvic nerve irritation.

PMID- 9566424
TI  - Absence of the G209A mutation in the alpha-synuclein gene in British families
      with Parkinson's disease.

PMID- 9566425
TI  - Olanzapine can worsen parkinsonism.

PMID- 9566426
TI  - Delayed stimulation-induced thalamic ataxia syndrome.

PMID- 9566427
TI  - Audible pulsatile tinnitus in idiopathic intracranial hypertension.

PMID- 9566428
TI  - Dissociation of gesture and object recognition.

PMID- 9566429
TI  - Response to corticosteroid therapy in a patient with HTLV-I-associated motor
      neuron disease.

PMID- 9566430
TI  - Neurologic symptoms mistaken for gastrointestinal disease.

PMID- 9566431
TI  - Pachymeningitis with a perinuclear antineutrophil cytoplasmic antibody: response
      to pulse steroid.

PMID- 9566432
TI  - Alternative uses of lamotrigine and gabapentin in the treatment of trigeminal
      neuralgia.

PMID- 9566433
TI  - What are the obstacles for an accurate clinical diagnosis of Pick's disease?

PMID- 9566434
TI  - Jaw clenching following Gamma Knife treatment for trigeminal neuralgia.

PMID- 9566435
TI  - Lacunes due to dilatations of perivascular spaces.

PMID- 9566436
TI  - Drugs acting at the glycine site on the NMDA receptor as cognitive enhancers in
      patients with Alzheimer's disease.

PMID- 9566437
TI  - Olanzapine in the treatment of dopaminomimetic psychosis in patients with
      Parkinson's disease.

PMID- 9566438
TI  - Assessing response to chemotherapy in malignant glioma: the role of steroids.

PMID- 9566439
TI  - Assessing response to chemotherapy in malignant glioma: the role of steroids.

PMID- 9566440
TI  - Computer-aided video angiometry in isolated rabbit hearts: a new method assessing
      epicardial coronary selectivity.
AB  - The clinical value of coronary vasodilators in antianginal therapy depends on the
      ratio of their epicardial versus resistance coronary vessel actions. The coronary
      flow measured in standard isolated heart preparations, however, does not allow
      any conclusion about the function of epicardial vessels. Thus, we established a
      new technique assessing the epicardial coronary diameter directly by video
      angiometry. Pictures from the cardiac surface were taken by a videocamera mounted
      on a long-distance microscope. The video signal was digitized for computer-aided
      evaluation. An area of interest (AOI) was laid over the vascular section to be
      measured. The gray values of the pixels across the epicardial vessel were
      registered, and a mean curve of distribution was obtained by averaging the gray
      values from all video lines within the AOI. The inner epicardial coronary
      diameter resulted from the distance between the points of inflection of this mean
      curve of distribution. Experiments with NO-vasodilators and adenosine showed that
      epicardial coronary arteries of isolated perfused rabbit hearts have no
      appreciable tone. Pretreatment of the hearts with a combination of histamine (10[
      6] mol/l), cimetidine (10[-5] mol/l), and adenosine (10[-7] mol/1), however,
      caused a marked contraction of the conductive vessels. NO-donors selectively
      dilated epicardial vessels in such pretreated hearts whereas adenosine increased
      both epicardial coronary diameter and coronary flow, with only a slight tendency
      toward preferential action on resistance vessels in low concentrations.
      Simultaneous registration of coronary flow and epicardial coronary diameter in
      isolated rabbit hearts pretreated with a spasmogenic drug combination (histamine,
      cimetidine, and adenosine) may be a feasible method assessing epicardial
      selectivity of coronary vasodilators.

PMID- 9566441
TI  - Rapid changes in intracellular Zn2+ in rat hepatocytes.
AB  - Changes in the concentration of free Zn2+ were monitored in isolated rat
      hepatocytes using the fluorescent indicator zinquin (ethyl[2-methyl-8-p
      toluenesulphonamido-6-quinolyloxy]acetat e). The concentration of Zn2+ in freshly
      isolated hepatocytes was 1.3 x 10(-6) M (range 0.61-2.7 x 10[-6] M). This value
      decreased by about 10%-15% during incubation in the absence of zinc and increased
      in a time- and concentration-dependent manner in the presence of exogenous zinc
      (Km approximately 10 microM). IIb group metal ions led to a concentration
      dependent increase in zinquin fluorescence. The rank of efficacy was Hg
      approximately Cd > Pb (IVa) >> Cu (Ib) >>> Ni (VIII). This rank resembles their
      ability to mobilize zinc from metallothioneins. 8-Br-3',5'-cAMP (10[-4]M) caused
      a rapid decrease in Zn2+ epifluorescence which was apparent within 10 min and was
      sustained throughout the experiment. This effect was gradually obliterated in the
      presence of external ZnCl2. The effect was specific for cAMP (or cAMP generating
      hormones) as the calcium-dependent hormone [arg8]vasopressin (5 x 10[-8] M) did
      not affect intracellular Zn2+. An integrated role of zinc as a possible mediator
      in signal transduction is discussed.

PMID- 9566442
TI  - In vitro analysis of the activity of the major human hepatic CYP enzyme (CYP3A4)
      using [N-methyl-14C]-erythromycin.
AB  - Although the N-demethylation of erythromycin has found widespread use in a
      noninvasive assay with which to phenotype hepatic CYP3A function, currently, the
      routine in vitro analysis of erythromycin N-demethylase activity relies on the
      quantitation of liberated formaldehyde by relatively labor-intensive and
      insensitive colorimetric or fluorimetric detection. This report describes the
      development of a rapid, sensitive, and reproducible radioassay for human CYP3A4
      using solid-phase extraction (SPE). The kinetics of erythromycin N-demethylation
      were best described by a one-site Michaelis-Menten model with autoinhibition and
      the apparent kinetic parameters for pooled human liver microsomes (HLM; Km=88
      microM, Vmax=345 pmol/min/mg) and expressed CYP3A4 (Km=33 microM, Vmax=130
      pmol/min/ mg) were in good agreement. Erythromycin N-demethylase activity was
      found to vary 14-fold in HLM and correlated with the rate of testosterone 6beta
      hydroxylation (r2=0.92, p < 0.001; N=9). Ketoconazole was a potent inhibitor of
      the N-demethylation of erythromycin, and the estimated IC50 value (104+/-23 nM)
      agreed well with that obtained using testosterone as a probe for CYP3A (71+/-4
      nM). The addition of this radioassay to those established for human CYP1A2, 2C9,
      2D6, and 2E1 and its subsequent automation should enable the routine use of this
      methodology in the analysis of CYP-dependent reactions.

PMID- 9566443
TI  - Tobacco smoke influence on heart rate, body temperature, and locomotor activity
      daily rhythms as assessed by radiotelemetry in rats.
AB  - Using radiotelemetry, this study aimed to evaluate the influence of tobacco smoke
      on heart rate (H), body temperature (T) and locomotor activity (A) daily rhythms
      in rats. The tobacco smoke intoxication was produced with a smoking apparatus. H,
      T, and A data were captured by radiotelemetry. The study was divided into three
      periods: a 1-week control period (P1), a 1-week stress period (P2), in order to
      evaluate the stress induced by the animals' restraint in the smoking apparatus,
      and a 1-week daily tobacco smoke intoxication period (P3). For P1, P2, and P3, a
      power spectrum analysis was applied in order to determine the dominant period of
      rhythmicity. Then, characteristics of the rhythms were determined by cosinor
      analysis. Statistical comparisons were done by ANOVA. Power spectrum analysis
      showed that neither stress nor tobacco suppressed the daily rhythmicity. Cosinor
      revealed some modifications: H amplitude was decreased during P2 and P3 with a
      greater reduction during P3, while T and A amplitudes were decreased during P2
      and P3 without difference between P2 and P3. T acrophase was delayed during P2,
      while A acrophase was delayed during P2 and P3 without any difference between P2
      and P3. These perturbations may reflect the effects of stress and tobacco on the
      suprachiasmatic nucleus by a dopaminergic mechanism.

PMID- 9566444
TI  - QT corrected for heart rate and relation between QT and RR intervals in beagle
      dogs.
AB  - The beagle dog has been widely used in cardiovascular research, but the adequacy
      of QT prediction formulas in dogs over a wide range of RR intervals has not been
      evaluated sufficiently. We investigated the QT-RR relation in beagles by analysis
      of the QT and preceding RR intervals obtained from 24-h ambulatory
      electrocardiograms. The acceptability of 14 QT prediction formulas was evaluated
      by use of 100-150 selected pairs of QT-RR points per animal in seven male and
      seven female beagles. The accuracy of fit with the measured data was assessed
      according to the minimum Akaike information criterion. The best fit was given by
      the logarithmic and inverse Kovacs' formulas among one- and two-parameter linear
      regression equations, respectively. Exponential formulas produced a better fit
      than did the linear regression formulas, but are impractical because of the
      complicated interpretation of parameters due to the nonlinearity. In addition,
      the results obtained under physiological conditions were also confirmed by those
      of the pharmacological intervention study with disopyramide. Consequently, we
      propose a one-parameter logarithmic formula (QTc= log600 x QT/logRR) for
      correcting the QT interval for a heart rate of 100 bpm and the inverse Kovacs'
      formula for evaluating a reverse-use-dependency of QT prolongation.

PMID- 9566445
TI  - A novel computer-controlled conditioned avoidance apparatus for rats.
AB  - Described and evaluated here is a newly designed apparatus for the assessment of
      conditioned avoidance response (CAR) performance in rats. The system is computer
      assisted using a design and system control development package based on the
      virtual instrument concept (LabView). The program, which allows for significant
      flexibility, greatly facilitated and simplified the process of timing and data
      acquisition. The apparatus was found effective and appropriately designed for CAR
      performance training, as well as for a reliable assessment of the effects of
      antipsychotic and potentially antipsychotic compounds on CAR in rats. The design
      presents a new, effective, and inexpensive option for laboratories involved in
      animal behavioral research.

PMID- 9566446
TI  - An international comparison of physicians' judgments of outcome rates of cardiac
      procedures and attitudes toward risk, uncertainty, justifiability, and regret.
AB  - OBJECTIVE: Compare U.K. and U.S. physicians' judgments of population
      probabilities of important outcomes of invasive cardiac procedures; and values
      held by them about risk, uncertainty, regret, and justifiability relevant to
      utilization of cardiac treatments. DESIGN: Cross-sectional study. SETTING:
      University hospital and VA medical center in the United States; two teaching
      hospitals in the United Kingdom. PARTICIPANTS: 171 housestaff and attendings at
      U.S. teaching hospitals; 51 physician trainees and consultants at U.K. hospitals.
      MEASURES: Judgments of probabilities of severe complications and deaths due to
      Swan-Ganz catheterization, cardiac catheterization, percutaneous transluminal
      coronary angioplasty (PTCA), and coronary artery bypass grafting (CABG);
      judgments of malpractice risks for case vignettes; Nightingale's risk-aversion
      instrument; Gerrity's reaction-to-uncertainty instrument; questions about need to
      justify decisions; responses to case vignettes regarding regret. RESULTS: The
      U.S. physicians judged rates of two bad outcomes of cardiac procedures
      (complications due to cardiac catheterization; death due to CABG) to be
      significantly higher (p < or = 0.01) than did the U.K. physicians (U.S. medians,
      5 and 3.5, respectively; U.K. medians 3 and 2). The median ratio of (risk of
      malpractice suit I error of omission)/(risk of suit I error of commission) judged
      by U.K. physicians, 3, was significantly (p=0.0006) higher than that judged by
      U.S. physicians, 1.5. The U.K. physicians were less often risk-seeking in the
      context of possible losses than the U.S. physicians (odds ratio for practicing in
      the U.K. as a predictor of risk seeking 0.3, p=0.003). The U.K. physicians had
      significantly more discomfort with uncertainty than did the U.S. physicians, as
      reflected by higher scores on the stress scale (U.K. median 48, U.S. 42,
      p=0.0001) and the reluctance-to-disclose-uncertainty scale (U.K. 40, U.S. 37, p <
      0.0001) of the Gerrity instrument. There was no clear international difference in
      perceived need to justify decisions, or in regret. CONCLUSIONS: The results were
      not clearly consistent with the uncertainty hypothesis that international
      practice variation is due to differences in judged rates of outcomes of therapy
      or with the imperfect-agency hypothesis that practice variation is due to
      differences in physicians' personal values. The causes and implications of
      practice variations remain unclear.

PMID- 9566447
TI  - Public preferences for prevention versus cure: what if an ounce of prevention is
      worth only an ounce of cure?
AB  - BACKGROUND: The belief that small preventive efforts bring large benefits may
      explain why many people say they value prevention above all other types of health
      care. However, it often takes a great deal of preventive medicine to prevent a
      bad outcome. This study explores whether people value prevention or cure more
      when each brings the same magnitude of benefit and examines whether preferences
      for prevention or cure vary according to the severity of the disability of the
      patients who can receive the preventive or curative intervention. METHODS: 289
      prospective jurors were presented with a policy dilemma involving how best to
      allocate funds to benefit people with varying levels of disability. Each project
      was said to influence the functional ability of 100 nursing home residents,
      either by improving their level of function or by preventing their level of
      function from declining. RESULTS: When given a choice between preventive and
      curative interventions, more subjects preferred the preventive intervention (37%
      vs 21%, p=0.002). However, when the strength of people's preferences was taken
      into account, the preference for preventive interventions was not statistically
      significant (p=0.135). With both preventive and curative interventions, the
      subjects preferred helping patients with more severe disabilities (p < 0.005 for
      both comparisons). This preference for helping more severely disabled patients
      did not differ for prevention and cure (p=0.663). CONCLUSION: When the magnitude
      of benefit was held constant, the subjects slightly preferred prevention over
      cure. In addition, they preferred directing limited resources toward those with
      greater disabilities, regardless of whether those resources were targeted toward
      prevention or cure. These findings suggest that previously stated preferences for
      prevention over cure may result from a belief that small efforts at prevention
      will be repaid by large reductions in the later need for cure.

PMID- 9566448
TI  - Physicians' diagnostic judgments and treatment decisions for acute otitis media
      in children.
AB  - Physicians' diagnoses of acute otitis media (AOM) and their treatment choices
      were investigated using judgment and decision-making analyses. Thirty-two
      pediatricians in the Albany, New York, area provided probability judgments of the
      presence of AOM and made treatment decisions for 32 patient vignettes, each
      described in terms of historical and examination variables. Their probability
      judgments were well predicted by linear combinations of the patient variables
      (R2s ranged from 0.76 to 0.97). Information about the observed condition of the
      eardrum proved to be most critical to the physicians' diagnoses. They
      demonstrated good levels of agreement on diagnoses. They varied, however, in
      their tendencies to treat with amoxicillin rather than another antibiotic. Case
      vagueness was related to the rate of antibiotic treatment. The rate of antibiotic
      treatment was higher for vague than for non-vague cases when the mean judged
      probability of AOM was low. In combination, the findings highlight the importance
      of performing and interpreting ear examinations and the role that consistent
      training may have in improving management of AOM.

PMID- 9566449
TI  - The role of clinical "experience" in diagnostic performance.
AB  - Twenty-one physicians examined records of 43 patients who had attended the
      hospital because of chest pain. Of these patients, 20 had had coronary heart
      disease (CHD), 15 had had nonspecific pain, and eight had had pulmonary embolism.
      The physicians indicated the probability of CHD in each case on the basis of 18
      clinical findings, not including ECG, x-ray, or biochemical studies. The trial
      was repeated five years later, using the same records, by 16 of the same
      physicians. Diagnostic accuracy was evaluated by ROC curves, and the weight
      ascribed to each cue was inferred by multiple regression with estimated
      probability of CHD as the dependent variable. No significant change of areas
      under the ROC curves with increasing length of clinical experience was observed.
      Multiple regression was significant in 30 of 37 analyses. The distributions of
      most physicians' estimates of probabilities had similar shapes five years apart.
      It is concluded that "experience" does not have a clear role in diagnostic
      performance based on recorded data and that personal calibration and preferences
      in estimating probabilities often persist for years.

PMID- 9566450
TI  - Implicit discount rates of vascular surgeons in the management of abdominal
      aortic aneurysms.
AB  - A growing empirical literature has investigated attitudes towards discounting of
      health benefits with regard to social choices of life-saving and health-improving
      measures and individuals' time preferences for the management of their own
      health. In this study, the authors elicited the time preferences of vascular
      surgeons in the context of management of small abdominal aortic aneurysms, for
      which the choice between early elective surgery and watchful waiting is not
      straightforward. They interviewed 25 of a random sample of 30 Swedish vascular
      surgeons. Considerable variation in the time preferences was found in the choices
      between watchful waiting and surgical intervention among the otherwise very
      homogeneous group of surgeons. The discount rates derived ranged from 5.3% to
      19.4%. The median discount rate (10.4%) is similar to those usually reported for
      social choices concerning life-saving measures. The surgeons who were employed in
      university hospitals had higher discount rates than did their colleagues in
      county and district hospitals.

PMID- 9566451
TI  - Sequence effects, health profiles, and the QALY model: in search of realistic
      modeling.
AB  - The authors conducted an experiment to determine whether the sequence of
      presentation of states in a health profile would affect the valuations assigned
      to them. The empirical task was part of a large standardized experiment involving
      104 students. Thirteen health states were valued using two variations of the time
      tradeoff method. At the group level, a small but distinct overall effect of the
      sequence of the tradeoffs was detected after accounting for discounting effects.
      The respondents were not preference-indifferent concerning the sequence of health
      states presented. Detailed analysis at the individual level indicated that the
      overall sequence effect was attributable to two groups of respondents who were
      sensitive to the sequence of events. One small group, referred to as "best-things
      first" respondents, preferred the best years first; the other group, classified
      as "happy-end" respondents, preferred the reverse sequence. The majority of the
      respondents, however, were indifferent to the sequence. These results suggest
      that 1) in valuation experiments involving the time-tradeoff method and 2) in
      applying valuation results to the evaluation of real-life health consequences, a
      varying lifetime health profile may not be regarded as simply a chain of
      independent separately valued and discounted QALY periods. Even elementary
      valuation tasks cannot safely assume ignorance of prognosis, as the additive
      utility independence assumption of the QALY model does not hold. The sequence
      effect at least supplements the conventional general time-preference concept, and
      specific strategies are suggested to disentangle quantitatively the sequence
      effect and the time-preference effect.

PMID- 9566452
TI  - Decision and cost-utility analyses of surgical versus transcatheter closure of
      patent ductus arteriosus: should you let a smile be your umbrella?
AB  - Decision and cost-utility analyses considered the tradeoffs of treating patent
      ductus arteriosus (PDA) using conventional surgery versus transcatheter
      implantation of the Rashkind occluder. Physicians and informed lay parents
      assigned utility scores to procedure success/complications combinations seen in
      prognostically similar pediatric patients with isolated PDA treated from 1982 to
      1987. Utility scores multiplied by outcome frequencies from a comparative study
      generated expected utility values for the two approaches. Cost-utility analyses
      combined these results with simulated provider cost estimates from 1989. On a 0
      100 scale (worst to best observed outcome), the median expected utility for
      surgery was 99.96, versus 98.88 for the occluder. Results of most sensitivity
      analyses also slightly favored surgery. Expected utility differences based on
      1987 data were minimal. With a mean overall simulated cost of $8,838 vs $12,466
      for the occluder, surgery was favored in most cost-utility analyses. Use of the
      inherently less invasive but less successful, more risky, and more costly
      occluder approach conferred no apparent net advantage in this study. Analyses of
      comparable current data would be informative.

PMID- 9566453
TI  - Carrier screening for cystic fibrosis: costs and clinical outcomes.
AB  - OBJECTIVES: To evaluate the costs and clinical effects of 16 alternative
      strategies for cystic fibrosis (CF) carrier screening in the reproductive
      setting; and to test the sensitivity of the results to assumptions about cost and
      detection rate, stakeholder perspective, DNA test specificity, chance of
      nonpaternity, and couples' reproductive plans. METHOD: Cost-effectiveness
      analysis. RESULTS: A sequential screening strategy had the lowest cost per CF
      birth avoided. In this strategy, the first partner was screened with a standard
      test that identifies 85% of carriers. The second partner was screened with an
      expanded test if the first partner's screen was positive. This strategy
      identified 75% of anticipated CF births at a cost of $367,000 each. This figure
      does not include the lifetime medical costs of caring for a patient with CF, and
      it assumes that couples who identify a pregnancy at risk will choose to have
      prenatal diagnosis and termination of affected pregnancies. The cost per CF birth
      identified is approximately half this figure when couples plan two children.
      CONCLUSIONS: The cost-effectiveness of CF carrier screening depends greatly on
      couples' reproductive plans. CF carrier screening is most cost-effective when it
      is performed sequentially, when the information is used for more than one
      pregnancy, and when the intention of the couple is to identify and terminate
      affected pregnancies. These conclusions are important for policy considerations
      regarding population-based screening for CF, and may also have important
      implications for screening for less common diseases.

PMID- 9566454
TI  - Treatment of early-stage breast cancer in the elderly: a health-outcome-based
      approach.
AB  - PURPOSE: To evaluate the post-lumpectomy treatment of a nonpalpable, stage I, T1b
      tumor, mammographically detected, in a 74-year-old woman without comorbidities.
      METHODS: A Markov process, through 120 monthly cycles, was used to model patient
      progression through a treatment program, employing literature data and a health
      outcome utility. Treatments considered were: observation; radiation totaling
      5,000 cGy over six weeks; tamoxifen, 20 mg/day, for five years; simple
      mastectomy; and radiation therapy plus tamoxifen. Health states included absence
      of disease (NED), loco-regional recurrence, distant metastasis, age-sex-race
      (ASR)-adjusted death, cancer mortality, treatment complications, and post
      mastectomy death. Transition probabilities were established from the literature.
      Health-state utilities were determined from the responses of health care
      professionals to a basic reference gamble. RESULTS: Quality-adjusted life years
      (QALYs) were determined to be 8.19 for radiation plus tamoxifen, decreasing to
      8.04 for mastectomy, a difference of only a 0.15 years (1.8 months). Sensitivity
      analysis, however, showed relative stability in the ranking among treatment
      options. CONCLUSION: Although the model showed little difference between QALYs
      with the treatments, the combination of radiation and tamoxifen provides the
      optimal therapy for this case.

PMID- 9566455
TI  - Effect of an explicit decision-support tool on decisions to prescribe antibiotics
      for sore throat.
AB  - Studies of scoring rules for sore throat have failed to show that they lower
      antibiotic prescription rates. The authors studied the effect of an explicit
      decision-support tool, incorporating a modified score, on antibiotic-prescription
      decisions. Four hundred and fifty family physicians received an information
      package, a score card, and a recording form to use during one sore-throat
      encounter. The physicians randomly received either a control form or an
      intervention form that required them to interact with the score during the
      clinical recording process. There was a trend towards a reduction in antibiotic
      prescriptions (21%, p=0.09) in the physicians using the intervention form. A
      greater reduction (45%, p=0.06) was observed for patients whose probabilities of
      infection with group A streptococcus were low. Sore-throat-scoring rules may
      reduce unnecessary antibiotic prescriptions if physicians are specifically cued
      to use them during clinical encounters and appropriate management responses are
      linked to score estimates for the likelihood of group A streptococcus infection.

PMID- 9566456
TI  - Predicting mortality after coronary artery bypass surgery: what do artificial
      neural networks learn? The Steering Committee of the Cardiac Care Network of
      Ontario.
AB  - OBJECTIVE: To compare the abilities of artificial neural network and logistic
      regression models to predict the risk of in-hospital mortality after coronary
      artery bypass graft (CABG) surgery. METHODS: Neural network and logistic
      regression models were developed using a training set of 4,782 patients
      undergoing CABG surgery in Ontario, Canada, in 1991, and they were validated in
      two test sets of 5,309 and 5,517 patients having CABG surgery in 1992 and 1993,
      respectively. RESULTS: The probabilities predicted from a fully trained neural
      network were similar to those of a "saturated" regression model, with both models
      detecting all possible interactions in the training set and validating poorly in
      the two test sets. A second neural network was developed by cross-validating a
      network against a new set of data and terminating network training early to
      create a more generalizable model. A simple "main effects" regression model
      without any interaction terms was also developed. Both of these models validated
      well, with areas under the receiver operating characteristic curves of 0.78 and
      0.77 (p > 0.10) in the 1993 test set. The predictions from the two models were
      very highly correlated (r=0.95). CONCLUSIONS: Artificial neural networks and
      logistic regression models learn similar relationships between patient
      characteristics and mortality after CABG surgery.

PMID- 9566457
TI  - Rating scales in context.

PMID- 9566459
TI  - Confidentiality agreements and scientific independence.

PMID- 9566458
TI  - Producing informed consumers and users of decision analysis.

PMID- 9566460
TI  - Economics, pharmaceuticals, and pharmacoeconomics.

PMID- 9566461
TI  - Pharmacoeconomics and managed care: methodologic and policy issues.

PMID- 9566462
TI  - Experimental versus observational data in the economic evaluation of
      pharmaceuticals.

PMID- 9566463
TI  - Guidelines for measuring the costs and consequences of adopting new
      pharmaceutical products: are they on track?

PMID- 9566464
TI  - Paying the piper for pharmacoeconomic studies.

PMID- 9566465
TI  - Ex post value reimbursement for pharmaceuticals.
AB  - The paper examines the welfare properties of an ex post value regulation scheme
      in which a pharmaceutical firm's revenue varies with the social value of its
      product. The mechanism, which is a variant of that proposed by Loeb and Magat,
      leads to efficient investment in research and development (R&D), production,
      consumption, and promotion under certain market and technologic conditions. The
      mechanism's attractive simplicity is lost when account is taken of the rivalrous
      nature of R&D, the fact that drugs can be complements or substitutes, the excess
      cost of taxes needed to finance the mechanism, and the multinational character of
      most pharmaceutical firms.

PMID- 9566466
TI  - Predicting the cost of illness: a comparison of alternative models applied to
      stroke.
AB  - Predictions of cost over well-defined time horizons are frequently required in
      the analysis of clinical trials and social experiments, for decision models
      investigating the cost-effectiveness of interventions, and for macro-level
      estimates of the resource impact of disease. With rare exceptions, cost
      predictions used in such applications continue to take the form of deterministic
      point estimates. However, the growing availability of large administrative and
      clinical data sets offers new opportunities for a more general approach to
      disease cost forecasting: the estimation of multivariable cost functions that
      yield predictions at the individual level, conditional on intervention(s),
      patient characteristics, and other factors. This raises the fundamental question
      of how to choose the "best" cost model for a given application. The central
      purpose of this paper is to demonstrate how to evaluate competing models on the
      basis of predictive validity. This concept is operationalized according to three
      alternative criteria: 1) root mean square error (RMSE), for evaluating predicted
      mean cost; 2) mean absolute error (MAE), for evaluating predicted median cost;
      and 3) a logarithmic scoring rule (log score), an information-theoretic index for
      evaluating the entire predictive distribution of cost. To illustrate these
      concepts, the authors conducted a split-sample analysis of data from a national
      sample of Medicare-covered patients hospitalized for ischemic stroke in 1991 and
      followed to the end of 1993. Using test and training samples of about 500,000
      observations each, they investigated five models: single-equation linear models,
      with and without log transform of cost; two-part (mixture) models, with and
      without log transform, to directly address the problem of zero-cost observations;
      and a Cox proportional-hazards model stratified by time interval. For deriving
      the predictive distribution of cost, the log transformed two-part and
      proportional-hazards models are superior. For deriving the predicted mean or
      median cost, these two models and the commonly used log-transformed linear model
      all perform about the same. The untransformed models are dominated in every
      instance. The approaches to model selection illustrated here can be applied
      across a wide range of settings.

PMID- 9566467
TI  - Eliciting stated health preferences: an application to willingness to pay for
      longevity.
AB  - The economic analysis of many health policies requires evaluation of the benefits
      of programs that may prolong human lives. This article contributes to the
      development of credible values for longevity, demonstrating the feasibility of
      applying stated-preference market-research techniques to a new area of preference
      revelation and framing the problem as extending longevity under realistic health
      states associated with advanced age. Respondents to the authors' stated
      preference survey clearly indicated that quality of life affects the value of
      quantity of life. The results demonstrate the sensitivity of life-extension
      values to specific health and activity-limitation conditions. The article also
      discusses problems that remain to be solved before valid and reliable longevity
      values can be obtained.

PMID- 9566468
TI  - Net health benefits: a new framework for the analysis of uncertainty in cost
      effectiveness analysis.
AB  - In recent years, considerable attention has been devoted to the development of
      statistical methods for the analysis of uncertainty in cost-effectiveness (CE)
      analysis, with a focus on situations in which the analyst has patient-level data
      on the costs and health effects of alternative interventions. To date,
      discussions have focused almost exclusively on addressing the practical
      challenges involved in estimating confidence intervals for CE ratios. However,
      the general approach of using confidence intervals to convey information about
      uncertainty around CE ratio estimates suffers from theoretical limitations that
      render it inappropriate in many situations. The authors present an alternative
      framework for analyzing uncertainty in the economic evaluation of health
      interventions (the "net health benefits" approach) that is more broadly
      applicable and that avoids some problems of prior methods. This approach offers
      several practical and theoretical advantages over the analysis of CE ratios, is
      straightforward to apply, and highlights some important principles in the
      theoretical underpinnings of CE analysis.

PMID- 9566469
TI  - Power and sample size calculations for stochastic cost-effectiveness analysis.
AB  - As the data for economic analyses are increasingly collected prospectively
      alongside clinical trials, many commentators have highlighted that the sample
      sizes in such trials should be based on the requirements for the economic
      analysis as well as those for the clinical evaluation. However, issues associated
      with sample size calculations for economic analysis have yet to receive the
      rigorous attention given to sample size calculation for clinical evaluation. In
      particular, no sample size formula for cost-effectiveness analysis is available
      for analysts hoping either to calculate the required sample size at the design
      stage of a study or to calculate the power a given size of clinical trial will
      generate for cost-effectiveness analysis. Building on the recent literature for
      calculating confidence intervals for cost-effectiveness ratios, the authors
      explore possible techniques for deriving a sample size formula for cost
      effectiveness analysis based on simple combination of the confidence limits on
      costs and effects.

PMID- 9566470
TI  - A Monte Carlo simulation of advanced HIV disease: application to prevention of
      CMV infection.
AB  - BACKGROUND: Disagreement exists among decision makers regarding the allocation of
      limited HIV patient care resources and, specifically, the comparative value of
      preventing opportunistic infections in late-stage disease. METHODS: A Monte Carlo
      simulation framework was used to evaluate a state-transition model of the natural
      history of HIV illness in patients with CD4 counts below 300/mm3 and to project
      the costs and consequences of alternative strategies for preventing AIDS-related
      complications. The authors describe the model and demonstrate how it may be
      employed to assess the cost-effectiveness of oral ganciclovir for prevention of
      cytomegalovirus (CMV) infection. RESULTS: Ganciclovir prophylaxis confers an
      estimated additional 0.7 quality-adjusted month of life at a net cost of $10,700,
      implying an incremental cost-effectiveness ratio of roughly $173,000 per quality
      adjusted life year gained. Sensitivity analysis reveals that this baseline result
      is stable over a wide range of input data estimates, including quality of life
      and drug efficacy, but it is sensitive to CMV incidence and drug price
      assumptions. CONCLUSIONS: The Monte Carlo simulation framework offers decision
      makers a powerful and flexible tool for evaluating choices in the realm of
      chronic disease patient care. The authors have used it to assess HIV-related
      treatment options and continue to refine it to reflect advances in defining the
      pathogenesis and treatment of AIDS. Compared with alternative interventions, CMV
      prophylaxis does not appear to be a cost-effective use of scarce HIV clinical
      care funds. However, targeted prevention in patients identified to be at higher
      risk for CMV-related disease may warrant consideration.

PMID- 9566471
TI  - The drug treatment of alcohol withdrawal symptoms: a systematic review.
AB  - A computer-assisted and cross-reference literature search identified trials of
      therapy for alcohol withdrawal symptoms. Those with a randomized, double-blind
      placebo-controlled design were systematically assessed for quality of
      methodology. Fourteen studies were identified investigating 12 different drugs.
      The quality of methodological design, even among this highly selected group of
      published studies, was often poor. Study populations were generally under
      defined, most studies excluded severely ill patients, control groups were poorly
      matched, and the use of additional medication may have confounded results in some
      studies. Twelve different rating scales were used to assess severity of symptoms.
      All 12 compounds investigated were reported to be superior to placebo, but this
      has only been replicated for benzodiazepines and chlormethiazole. Further
      research using better methods is required to allow comparison of different drugs
      in the treatment of alcohol withdrawal symptoms. On the evidence available, a
      long-acting benzodiazepine should be the drug of first choice.

PMID- 9566472
TI  - Prior exposure to MK-801 sensitizes rats to ethanol-induced conditioned taste
      aversion.
AB  - Pretreatment with an uncompetitive NMDA receptor antagonist, dizocilpine [(+)MK
      801; six daily injections of 0.1 or 0.2 mg/kg, i.p.] significantly enhanced
      subsequent 1.5 g/kg ethanol-induced conditioned taste aversion (CTA). In a
      control experiment, dizocilpine (0.05-.2 mg/kg) produced only a marginal CTA.
      Thus, pre-exposure to low, non-aversive doses of MK-801 may sensitize rats to the
      aversive stimulus effects of ethanol.

PMID- 9566473
TI  - High sensitivity to gamma-hydroxybutyric acid in ethanol-preferring sP rats.
AB  - Sensitivity to the sedative effect of gamma-hydroxybutyric acid (GHB), an
      endogenous constituent of mammalian brain as well as an effective drug in the
      pharmacotherapy of alcoholism, was evaluated in rats of the selectively bred,
      ethanol-preferring sP and non-preferring sNP lines. GHB (0.75 and 1.0 g/kg) was
      administered i.p. to ethanol-naive sP and sNP rats. Times to lose (onset) and
      recover (sleep time) the righting reflex following GHB injection were measured.
      At both doses, sP rats showed a greater sensitivity to the effects of GHB than
      did sNP rats, as evidenced by significantly shorter onset and longer sleep time.
      The results of the present study indicate that genetically controlled sensitivity
      to the sedative effect of GHB is positively correlated to ethanol preference in
      sP and sNP rats and suggest a possible involvement of the brain GHB system in
      predisposition to ethanol preference.

PMID- 9566474
TI  - Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the
      cannabinoid antagonist SR-141716.
AB  - The present study assessed the efficacy of the cannabinoid CB1 receptor
      antagonist, SR-141716, in reducing voluntary ethanol intake in selectively bred
      Sardinian alcohol-preferring (sP) rats. Ethanol (10%, v/v) and food were
      available in daily 4 h scheduled access periods; water was present 24 h/day. The
      acute administration of a 2.5 and a 5 mg/kg dose of SR-141716 selectively reduced
      ethanol intake, whereas a 10 mg/kg dose of SR-141716 reduced to a similar extent
      both ethanol and food intake. These results suggest that the cannabinoid CB1
      receptor is involved in the mediation of the ethanol-reinforcing effects in sP
      rats.

PMID- 9566475
TI  - Saccharin drinking rather than open field behaviour predicts initial ethanol
      acceptance in Wistar rats.
AB  - This study examined the relationship between saccharin drinking, open field
      behaviour and ethanol drinking in Wistar rats. Correlational analysis revealed
      that both absolute saccharin drinking and an increase in total fluid intake in
      the presence of saccharin positively correlated with the initial acceptance of
      increasing ethanol concentrations in a two-bottle choice situation (2-8% v/v
      ethanol vs water). This relationship disappeared, however, during further weeks
      of ethanol drinking when ethanol was available in a three-bottle choice situation
      (8% ethanol vs 16% ethanol vs water). In contrast, none of the behavioural
      parameters measured in the open field test (forward locomotion, rearings, central
      entries, time in central area) correlated with subsequent ethanol consumption.
      These results indicate that saccharin drinking, rather than open field
      parameters, may predict subsequent ethanol intake during the initial period of
      exposure to low ethanol concentrations.

PMID- 9566476
TI  - Social climate on alcohol in Rotterdam, The Netherlands: public opinion on
      drinking behaviour and alcohol control measures.
AB  - Research was undertaken regarding the Dutch climate on alcohol in 1994 and
      results were compared with earlier findings. It was found that the social climate
      on alcohol in The Netherlands can be characterized by 'moderation'. Over the
      years, drinking without problems has become more acceptable (and is even
      encouraged at times) whereas excessive drinking and consequent problems still
      meet strong disapproval. Opinions concerning alcohol control measures mirror this
      attitude. Measures such as the restriction of drinking in public places and
      raising the age limits are endorsed by the public. However, more people are now
      against restrictions on the general availability of alcohol. Although drink
      driving has decreased over the years, its prevalence is still high, especially
      among those who are most at risk.

PMID- 9566477
TI  - Effects of fluvoxamine and citalopram in maintaining abstinence in a sample of
      Italian detoxified alcoholics.
AB  - A 16-week, randomized study was performed to test the efficacy of two selective
      serotonin reuptake inhibitors (SSRIs) fluvoxamine and citalopram, in decreasing
      relapse and craving in alcoholics, and to investigate possible differences in
      their clinical profile. After detoxification, each of the 81 patients (55 males
      and 26 females) was randomly assigned to one of three groups: 23 subjects did not
      receive any pharmacological treatment, 25 were treated with fluvoxamine,
      150mg/day, and 33 with citalopram, 20 mg/day. All patients received standard
      cognitive-behavioural therapy. Craving was assessed twice a month using a 10-step
      scale. Every intake of alcohol was considered a relapse and the subject was taken
      out of the study. At the end of the study, both the fluvoxamine and citalopram
      groups showed a statistically higher rate of continuous abstinence (63.6 and
      60.7%, respectively) compared to the group without pharmacological treatment
      (30.4%). Relapse severity did not differ among the three groups. Only citalopram
      showed a significant effect on craving throughout the study period. This study
      confirmed the efficacy of SSRIs as an adjunct to psychotherapy to prevent relapse
      in alcoholics. The relationship between the effects of these SSRIs on abstinence
      and craving, as well as the differences between their profiles, are discussed.

PMID- 9566478
TI  - A comparison of home detoxification and minimal intervention strategies for
      problem drinkers.
AB  - The Home Detoxification Service (HDS) established in central Scotland was
      introduced in response to a high admission rate of problem drinkers to the acute
      psychiatric wards in Bellsdyke Hospital. This paper reports the results of a
      comparison of two types of management for people referred to the HDS by local
      general practitioners (family doctors). Ninety-five patients referred to the HDS
      were randomly allocated to two groups of differing treatment intensities. With
      one group, the home detoxification (HD) programme was utilized and with the
      other, minimal intervention (MI) strategies were employed. Post-treatment outcome
      information collected after 6 months was examined in relation to drinking
      behaviour, changes in levels of alcohol-related problems and uptake of on-going
      support from other alcohol agencies. The majority of patients in both treatment
      groups demonstrated some degree of improvement in relation to these criteria and
      the most striking factor was that patients in the HD group remained abstinent
      twice as long after treatment as those in the MI group.

PMID- 9566479
TI  - Sensitivity of carbohydrate-deficient transferrin (CDT) in relation to age and
      duration of abstinence.
AB  - Carbohydrate-deficient transferrin (CDT) serum concentrations were prospectively
      determined in 162 subjects (alcoholics n=62, controls n=100) using three
      different methods of detection (IEF, CDTect, Axis%CDT). Repeated testing in
      alcoholics after 3 and 5 days of abstinence demonstrated a significantly higher
      sensitivity of CDT in patients above 40 years of age compared to younger
      patients.

PMID- 9566480
TI  - Reduced binocular depth inversion in patients with alcoholism.
AB  - Binocular depth inversion represents an illusion of visual perception, serving to
      invert the perception of implausible hollow objects, e.g. a hollow face into a
      normal face. Such inversion occurs frequently, especially when objects with a
      higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive
      factors are assumed to override the binocular disparity cues of stereopsis. The
      hypothesis was tested that during mild and moderate alcohol withdrawal, and
      severe and mild alcohol intoxication, the central nervous system is unable to
      correct implausible perceptual hypotheses. Measurements of binocular depth
      inversion in perception of three-dimensional objects were performed in 10
      patients with severe alcohol intoxication, in 10 subjects with mild alcohol
      intoxication, in nine patients with moderate alcohol withdrawal treated with
      carbamazepine, in 10 patients with moderate alcohol withdrawal without any
      pharmacological treatment, in 11 patients with mild alcohol withdrawal and in 10
      healthy volunteers. The binocular depth inversion scores were highly elevated in
      the severely intoxicated patients group and in the group with moderate withdrawal
      symptoms without carbamazepine treatment, in comparison to the healthy
      volunteers. The data demonstrate a strong impairment of binocular depth inversion
      in moderate alcohol withdrawal and during severe alcohol intoxication. This
      supports the view that these states may be accompanied by a disorganization of
      the interaction between sensory input and top-down component. The effects of
      carbamazepine are discussed.

PMID- 9566481
TI  - Population distribution of alcohol dehydrogenase class I in France: comparison
      with other populations, and distribution with respect to gender and age. The
      French Group for Research on Alcohol and Liver.
AB  - In Caucasians, a genetic polymorphism is known for some alcohol dehydrogenase
      (ADH) systems (beta and gamma). Knowledge of population frequencies of the beta
      and gamma hepatic isozyme variants in France is a prerequisite to understanding
      any role this genetic variation might play in determining the risk of alcohol
      related diseases. For the present study, the ADH phenotypes of 115 French
      Caucasian control subjects, consisting of 64 men and 51 women, were studied. The
      beta2 subunit was found to have a very low frequency. The relative frequencies of
      ADH gamma subunits observed in French Caucasians were found to be in good
      agreement with those already observed in other Caucasian populations. When gender
      and age were taken into account, a particular group corresponding to young men
      (age <50 years) was characterized by a manifest discordance with the comparable
      female population.

PMID- 9566483
TI  - Recombinant human erythropoietin: 10 years of clinical experience.
AB  - The need for a renewable source of erythropoietin to treat the anaemia of chronic
      renal failure was first recognized in the 1960s, but cloning and expression of
      the human gene was not achieved until 1983. Clinical testing of recombinant human
      erythropoietin (r-HuEPO) began in 1985, leading to the first licence as a
      therapeutic agent in 1988. The first clinical trials showed that an intravenous
      dose requirement of about 200 IU/kg/week would increase haemoglobin
      concentrations to 10-12g/dl in >90% of haemodialysis patients. Subcutaneous
      administration has subsequently been found to be effective, and may allow lower
      maintenance doses. It is now the route of choice in Europe, but not the USA. The
      best marker of benefit of the introduction of r-HuEPO is the reduction in need
      for regular blood transfusions. A marked improvement in anaemia-related symptoms
      has been clearly demonstrated. The most important factor in optimizing the
      response to r-HuEPO is iron supply. The marrow should be stimulated slowly, to
      allow mobilization of iron stores. Functional or absolute iron deficiency should
      be pre-empted by regular iron supplementation. It is also important to recognize
      resistant states induced by inflammation and bleeding, and to exclude severe
      hyperparathyroidism, aluminium overload and other haematological diseases. The
      most important adverse events associated with r-HuEPO are increased blood
      pressure and a possible increased risk of access failure. These are, however,
      challenges to improve practice, not reasons to avoid the use of r-HuEPO.

PMID- 9566482
TI  - Health Locus of Control in problem drinkers with and without liver disease.
AB  - The purpose of this study was to investigate whether patients who developed
      alcoholic liver disease have more awareness of the link between their behaviour
      and subsequent health than patients with non-alcoholic liver disease and people
      with drink problems with no liver disease. This study included three groups of
      patients, alcoholic liver disease (ALD) (n=57), non-alcoholic liver disease
      (n=77), and problem drinkers with no liver disease attending a London community
      day treatment centre (ACCEPT) (n=115). Health locus of control differentiates
      people into two groups, health externals who are individuals who maintain that
      their health is largely determined by external factors, as opposed to health
      internals, who believe that their behaviour plays a major role in determining
      their subsequent health or illness. The results of the Health Locus of Control
      (HLC) scale administered to the above subjects suggested that the ALD group had
      limited insight into the relationship between their drinking and subsequent liver
      disease, compared to the ACCEPT group. It is suggested that alcoholic liver
      disease patients receive counselling as part of their total management.

PMID- 9566484
TI  - Iron monitoring and supplementation: how do we achieve the best results?
AB  - A number of factors have been shown to limit the response to recombinant human
      erythropoietin (r-HuEPO). One major factor appears to be an inadequate iron
      supply to the bone marrow. Erythropoiesis is dependent upon a continuous supply
      of iron to the bone marrow. The rate at which iron can be drawn from existing
      stores may easily limit the rate of delivery for haemoglobin synthesis. This
      results in 'functional iron deficiency' which is distinct from 'absolute iron
      deficiency' caused by depletion of iron stores. At present there are three main
      parameters available to clinicians wishing to monitor iron status in their
      patients: serum ferritin and transferrin saturation (TFS), which are indirect
      measurements, and the percentage of hypochromic red cells, which directly
      reflects marrow iron status. Ferritin levels should be measured before starting r
      HuEPO therapy to ensure adequate iron stores (>200 microg/l), and when patients
      move from the correction phase to the maintenance phase of therapy (have stores
      become depleted during the correction phase?). In addition, ferritin levels can
      give an indication of iron overload following excess parenteral iron
      administration. The TFS represents a balance between iron supply by stores and
      demand by bone marrow. A saturation below 20% probably indicates iron-deficient
      erythropoiesis. However, this is an indirect measure of marrow iron supply and
      wide fluctuations have been observed when determined at different time points.
      The percentage of hypochromic red blood cells is measured by flow cytometry and a
      hypochromic subpopulation of more than 10% (normal percentage <2.5%) indicates
      iron-deficient erythropoiesis. However, not all departments may have access to
      the required equipment. The aim of iron supplementation is to provide sufficient
      iron for the correction phase and to replace iron losses (1500-2000 mg/year in
      haemodialysis patients) during the maintenance phase of r-HuEPO therapy. This
      amounts to a daily iron need in the range of 5 7 mg, which is well above the
      normal dietary intake and absorptive capacity of the human intestine. Therefore,
      there is a need for intravenous iron, in particular when the patient has absolute
      or functional iron deficiency, is intolerant of oral iron, or is not complying
      well with the oral regimen.

PMID- 9566485
TI  - Benefits and concerns of treating pre-dialysis and renal transplant patients with
      recombinant human erythropoietin.
AB  - The possibility of lower efficacy and the fear of an increased incidence of side
      effects may explain the reluctance to use recombinant human erythropoietin (r
      HuEPO) in patients with impaired renal function who do not yet require dialysis,
      as well as in transplanted patients with a failing renal allograft. Several
      recent studies have clearly shown that r-HuEPO is effective in these patient
      populations and that the doses needed to control anaemia are comparable with or
      lower than those needed for dialysis patients. When started at a low dose, the
      risk of severe hypertension is minimal, although in a significant number of
      patients intensification of the antihypertensive regimen is needed. Moreover,
      there are no indications that the use of r-HuEPO accelerates the deterioration of
      residual renal function.

PMID- 9566486
TI  - Optimal haemoglobin during treatment with recombinant human erythropoietin.
AB  - The optimal target haemoglobin during treatment with recombinant human
      erythropoietin (r-HuEPO) is still controversial. The impact of haemoglobin on
      cardiovascular function or survival, on physical performance and on medical
      rehabilitation have to be taken into consideration. Although currently there is
      no solid evidence to show that haemoglobin beyond that recommended by the ad hoc
      committee of the National Kidney Foundation improves survival, sound theoretical
      arguments can be offered for this proposition, particularly in cardiac patients.
      It is sensible to individualize the target haemoglobin and to avoid rapid
      correction of anaemia.

PMID- 9566487
TI  - Meeting the challenges of a new millennium: optimizing the use of recombinant
      human erythropoietin.
AB  - Optimizing the use of recombinant human erythropoietin (r-HuEPO) involves
      choosing an appropriate dose regimen and target haemoglobin level, addressing
      factors that inhibit response, and considering appropriate adjuvant therapy.
      Subcutaneous administration of r-HuEPO two or three times weekly is optimal for
      most patients. Early detection and treatment of iron deficiency is mandatory.
      Measurement of the percentage of hypochromic red blood cells is a reliable marker
      of functional iron deficiency, and the treatment of choice is intravenous iron.
      Other factors that can affect the response to r-HuEPO include blood loss
      (sometimes occult), infection, inflammation, hyperparathyroidism with marrow
      fibrosis, aluminium toxicity, vitamin B12/folate deficiency, haemolysis, bone
      marrow disorders, haemoglobinopathies, under-dialysis and possibly angiotensin
      converting enzyme inhibitors. These factors should be identified and corrected
      where possible. Ascorbic acid, vitamin D, folic acid, carnitine, other cytokines
      and growth factors have all been shown to augment the response to r-HuEPO in some
      patients. Further research is required before any of these adjuvant therapies can
      be incorporated into routine clinical practice. With regard to target haemoglobin
      value, the current practice is to aim for a level of 10-12 g/dl, but it may be
      argued that a higher target would achieve greater benefits in terms of physical
      performance, quality of life, and possibly cardiac morbidity and mortality.
      International multicentre trials are currently in progress to address this issue,
      as are studies on other substances that may be able to stimulate erythropoiesis.

PMID- 9566488
TI  - Salmonella infection-induced non-responsiveness of murine splenic T-lymphocytes
      to interleukin-2 (IL-2) involves inhibition of IL-2 receptor gamma chain
      expression.
AB  - In a previous study we demonstrated that Salmonella typhimurium-induced
      immunosuppression involved T-cell non-responsiveness to interleukin-2 (IL-2). In
      this study we observed that Salmonella-induced T-cell non-responsiveness to IL-2
      was not reversed completely by treatment with N(G)-monomethyl-L-arginine, which
      is known to inhibit nitric oxide (NO) secretion by macrophages in culture.
      Furthermore, when purified splenic T-lymphocytes from Salmonella-infected mice
      were activated with an anti-CD3 antibody, the responsiveness of these T-cells to
      IL-2 was suppressed significantly. Results of flow cytometric analysis using an
      anti-IL-2 receptor gamma chain (IL-2Rgamma) antibody showed that IL-2Rgamma
      expression in mitogen-activated T-cells was down-regulated by Salmonella
      infection. These results suggest that Salmonella infection-induced T-cell non
      responsiveness to IL-2 involves a defective function of T-cells themselves and
      appears to be regulated by inhibition of IL-2Rgamma expression in T-cells.

PMID- 9566489
TI  - Morphological effects of itraconazole on murine macrophage.
AB  - Morphological effects of itraconazole (ITCZ) on murine macrophages were examined
      by light microscopy (LM), scanning electron microscopy (SEM) and transmission
      electron microscopy (TEM), and compared with the effects of other antifungal
      agents. Thioglycolate-induced peritoneal macrophages were prepared from C3H/He J
      mice and cultured for 20 h in the presence of the antifungal azoles econazole,
      fluconazole, miconazole, ketoconazole, ITCZ, hydroxy-itraconazole (ITCZ-OH), and
      a polyene antibiotic amphotericin B (AMPH). Among these reagents, only ITCZ and
      its derivative ITCZ-OH were effective in causing morphological changes of murine
      macrophage as determined by LM and SEM. Macrophages treated with 2 microg/ml ITCZ
      or ITCZ-OH were stretched out bidirectionally, their surface was smooth and their
      'ruffles' decreased. TEM observation showed that the bundles of the filamentous
      structure existed along the cell shape in the cytoplasm. These findings suggest
      that ITCZ and ITCZ-OH affect the morphology of macrophages.

PMID- 9566490
TI  - Macrophages recognize and adhere to an OmpD-like protein of Salmonella
      typhimurium.
AB  - Murine peritoneal macrophages bind to Salmonella typhimurium in vitro in the
      absence of exogenous opsonins. We have identified an outer membrane protein of S.
      typhimurium that mediates this adhesion. Biotin-labeled macrophages were used to
      probe electroblotted envelope proteins of S. typhimurium that had been previously
      resolved by polyacrylamide electrophoresis under denaturing and reducing
      conditions. Macrophages bound to an outer membrane protein with an apparent
      molecular mass of 44 kDa. The protein was purified to homogeneity and free of
      detectable lipopolysaccharide. Limited microsequencing of this protein resulted
      in a 15-amino acid query sequence of A-E-V-Y-N-K-D-G-N-K-L-D-L-Y-G, which shares
      complete identity with a 15-mer of both the OmpD of S. typhimurium SH 7454 and
      the OmpC polypeptide of Escherichia coli K-12. Picomolar concentrations of this
      purified protein significantly inhibited the subsequent adherence of 35S-labeled
      S. typhimurium to macrophages in monolayers. We propose that this 44-kDa protein
      is involved in the recognition of S. typhimurium by macrophage during the initial
      stages of infection.

PMID- 9566491
TI  - Development and evaluation of a multiplex PCR assay for rapid detection of
      toxigenic Vibrio cholerae O1 and O139.
AB  - A multiplex polymerase chain reaction assay was developed for concurrent
      detection of rfb sequences specific for the O1 and the O139 serogroups of Vibrio
      cholerae and for ctxA specific sequences. The multiplex PCR assay was found to be
      highly specific and sensitive and was capable of detecting 65 cfu and 200 cfu per
      assay of V. cholerae O1 and O139, respectively. Evaluation of the multiplex PCR
      assay using 121 stool samples from patients admitted to the Infectious Diseases
      Hospital, Calcutta, showed the assay to be 100% sensitive and 95.2% specific when
      the culture method was taken as the standard. In addition to the 38 PCR positive
      stool samples, an additional four samples which were negative by culture method
      but positive by PCR assay belonged to the O139 serogroup. All the 38 stool
      samples positive for either O1 or O139 serogroup by PCR assay were also positive
      for the ctxA amplicon indicating that the O1 and O139 V. cholerae strains have
      the genetic potential of producing cholera toxin.

PMID- 9566492
TI  - The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised
      by Th1 cells in humans with naturally acquired immunity to L. major.
AB  - The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen,
      which can induce Th1-mediated protection against murine leishmaniasis when used
      as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell
      response to PSA-2 was characterised in individuals immune to cutaneous
      leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with
      a past history of self-healing cutaneous leishmaniasis proliferated vigorously in
      response to PSA-2 isolated from Leishmania major, whereas the antigen did not
      activate cells from presumably unexposed Danes. Peripheral blood mononuclear
      cells from individuals with previous L. major infection had varying proliferative
      responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood
      mononuclear cells activated by PSA-2 from L. major produced high amounts of
      interferon-gamma and tumour necrosis factor-beta, and little interleukin-4,
      thereby showing a Th1 cytokine pattern. Parallel cultures showed clear Th1 and
      Th2 response patterns to purified protein derivative of tuberculin or tetanus
      toxoid, respectively. Flow cytometric analysis revealed that PSA-2 induced
      blastogenesis in the CD3 positive population and that these cells were the major
      source of interferon-gamma. The results show that Th1-like cells recognising PSA
      2 are expanded during infection by L. major and that they maintain their Th1-like
      cytokine profile upon reactivation in vitro. Since immunity to cutaneous
      leishmaniasis is mediated by antigen-specific Th1-like cells, PSA-2 might be
      considered a vaccine candidate for human leishmaniasis.

PMID- 9566493
TI  - Analysis of the interaction of Aeromonas caviae, A. hydrophila and A. sobria with
      mucins.
AB  - Aeromonas species are known to be involved in human gastrointestinal diseases.
      These organisms colonize the gastrointestinal tract. Aeromonas hydrophila, A.
      caviae, and A. sobria have been demonstrated microscopically to adhere to animal
      cell lines that express mucous receptors, but quantitative studies of adherence
      to mucosal components such as mucin have not been published to date. Purified
      bovine submaxillary gland, hog gastric mucin, and fish skin mucin were used as a
      model to study mucin-binding activity among A. caviae, A. hydrophila, and A.
      sobria strains. Our findings revealed that binding of radiolabeled and enzyme
      conjugated mucins to Aeromonas cells varied depending on the labeling procedure.
      The highest binding was observed when the three mucin preparations were labeled
      with horseradish peroxidase. Binding of the various horseradish peroxidase
      labeled mucins by A. caviae, A. hydrophila, and A. sobria cells is a common
      property among Aeromonas species isolated from human infections, diseased fish,
      and from environmental sources. The proportion of Aeromonas strains which bind
      the various horseradish peroxidase-labeled mucins was significantly higher for A.
      hydrophila than for A. caviae and A. sobria. Bacterial cell-surface extracts
      containing active mucin-binding components recognized the horseradish peroxidase
      labeled mucins. The molecular masses of the mucin-binding proteins were estimated
      by SDS-PAGE and Western blot as follows: A. caviae strain A4812 (95 and 44 kDa);
      A. hydrophila strain 48748 (97, 45, 33 and 22 kDa); and A. sobria strain 48739
      (95 and 43 kDa). Mucin interaction with Aeromonas cells was also studied in terms
      of growth in mucin-rich media. The culture conditions greatly influence the
      expression of A. hydrophila mucin-binding activity.

PMID- 9566495
TI  - Presumptive identification of an emerging yeast pathogen: Candida dubliniensis
      (sp. nov.) reduces 2,3,5-triphenyltetrazolium chloride.
AB  - Developments in medical intervention and the increasing population of patients
      with immunodeficiencies and transient or long-term immunosuppression have
      increased the list of yeast species that can cause disease. Candida dubliniensis
      is a novel species with close genetic relatedness to C. albicans. The two species
      share many common physiological and biochemical properties thus making their
      distinction cumbrous. A rapid and inexpensive way to presumptively differentiate
      between the two species, having previously performed a germ tube test, is the
      ability of C. dubliniensis to reduce the tetrazolium salt and it is reported for
      the first time. Microbiological information about new and emerging yeast
      pathogens, including rapid means for their identification, equips medical
      microbiologists with the means to identify and physicians to treat effectively
      infections attributed to unusual yeasts.

PMID- 9566494
TI  - Mycobacterial crossreactivity of M. tuberculosis reactive T cell clones from
      naturally converted PPD positive healthy subjects.
AB  - Mycobacterium tuberculosis reactive CD4+, CD8- T cell clones were established
      from six naturally converted PPD positive healthy subjects by using whole bacilli
      as the primary stimulation antigen in vitro. Antigen specificity of the T cell
      clones was mapped by testing their proliferative response against a panel of
      pathogenic and environmental mycobacterial species. The crossreactivity patterns
      obtained showed that the T cell clones distributed along a spectrum from
      reactivity restricted to the M. tuberculosis complex to broadly crossreactive
      clones recognizing all mycobacterial species tested. Two of the T cell clones
      were able to discriminate between M. tuberculosis and M. bovis BCG, and
      importantly one of these clones was exclusively specific to M. tuberculosis. All
      of the CD4+ T cell clones tested, displayed MHC class II restricted cytotoxicity
      against macrophages pulsed with M. tuberculosis. In addition, some of these
      clones secreted GM-CSF upon antigen stimulation. The T cell clones described here
      represent relevant tools to identify and characterize target antigens of the
      immune response against M. tuberculosis with relevance to diagnosis and subunit
      vaccine design.

PMID- 9566496
TI  - Oxidized glutathione promotes sleep in rabbits.
AB  - Glutatione is implicated in sleep regulation. There are circadian changes in
      brain glutathione levels, and nocturnal intracerebroventricular (i.c.v.) slow
      infusion of oxidized glutathione (GSSG) or reduced glutathione (GSH) promotes
      rapid-eye-movement sleep (REMS) and non-REMS (NREMS) in rats. In the present
      experiments, we tested the effects of GSSG on duration of sleep, NREMS intensity,
      and brain temperature in another species, rabbits. Male New Zealand rabbits were
      injected with isotonic NaCl on a baseline day and one dose of GSSG on the test
      day [0.15, 1.5, 15, and 150 microg/rabbit, i.c.v., or 1.5 or 15 mg/kg
      intravenously (i.v.)]. Electroencephalogram (EEG), motor activity, and brain
      temperature were recorded for 6 h. Injection of 15 microg GSSG i.c.v.
      significantly increased the time spent in NREMS in the first 3 h after the
      injection. Injection of 0.15, 1.5, and 150 microg i.s.v. GSSG, as well as
      systemic injections of GSSG did not affect NREMS. Intensity of NREMS as measured
      by EEG slow-wave activity during NREMS, and brain temperature were not affected
      by any of the treatments. These results are consistent with the hypothesis that
      glutathione may be a sleep-inducing factor in the brain.

PMID- 9566497
TI  - Self-stimulation from the mesencephalon following intraventricular interleukin-2
      administration.
AB  - Intracranial self-stimulation was evaluated among CD-1 mice responding for brain
      stimulation from the dorsal and ventral aspects of the ventral tegmental area
      (VTA). Intraventricular interleukin-2 (IL-2) administration (5 ng) in a 1-microl
      volume elevated the stimulation frequency required to effect half-maximal
      responding for brain stimulation from the dorsal A10 region 15 min, 24 h, 48 h,
      and 1 week following drug administration relative to vehicle-treated animals.
      Intraventricular IL-2 administration did not influence responding for brain
      stimulation from the ventral A10 area, and performance of these animals was
      indistinguishable from the performance of vehicle-challenged animals implanted
      with a stimulating electrode in the ventral A10 area. These data suggest that
      central IL-2 administration reduces the value of previously rewarding brain
      stimulation from subregions of the VTA. The implications of these data for
      behavioural pathology are discussed.

PMID- 9566498
TI  - Alterations in catecholamine turnover in specific regions of the rat brain
      following acute exposure to nitrous oxide.
AB  - The effects of nitrous oxide (N2O) on steady-state concentrations and turnover
      rates of catecholamines in the olfactory bulb, hypothalamus, brain stem,
      hippocampus, striatum, thalamus, cerebral cortex, and spinal cord were determined
      in rats. Animals were exposed for 2 h to either 60% N2O or air. Immediately
      following exposure, all animals were injected intraperitoneally with alpha
      methylparatyrosine (alphaMPT), a competitive inhibitor of tyrosine hydroxylase,
      and sacrificed at 0, 30, or 90 min postinjection. Brain catecholamine
      concentrations were determined using high-performance liquid chromatography
      coupled with electrochemical detection (HPLC-EC). Results indicate that N2O
      exposure significantly elevates steady-state concentrations of norepinephrine
      (NE) in the hypothalamus and striatum yet decreases amine levels in the brain
      stem region. Steady-state levels of dopamine (DA) were not significantly altered
      in any region of the CNS by N2O exposure. Acute exposure to N2O also resulted in
      significant decreases in the turnover rate of NE in the brain stem, yet it
      increased turnover of this amine in the olfactory bulb, hypothalamus, and
      striatum. Acute exposure to N2O resulted in a decreased turnover rate of DA in
      the hippocampus and striatum. In contrast, N2O appears to increase DA turnover in
      the olfactory bulb. These results indicate that acute exposure to N2O in rats
      causes region-specific alterations in steady-state levels and turnover rates of
      DA and NE within the central nervous system.

PMID- 9566499
TI  - Substance P- and calcitonin gene-related peptide-containing nerve fibers in the
      nasal mucosa of chronically hypoxic rats.
AB  - The distribution of substance P-immunoreactive and calcitonin gene-related
      peptide-immunoreactive nerve fibers in the nasal mucosa was compared between
      normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). In
      the normoxic nasal mucosa, substance P- and calcitonin gene-related peptide
      immunoreactive nerve fibers were found within and under the epithelium and around
      the glands and blood vessels in the lamina propria. These immunoreactive fibers
      have many varicosities. In the chronically hypoxic nasal mucosa, the relative
      density of intra- and subepithelial substance P-immunoreactive and calcitonin
      gene-related peptide-immunoreactive fibers and those in the lamina propria was
      higher than in normoxic mucosa. The length of substance P-positive fibers within
      the chronically hypoxic olfactory and respiratory epithelium was 1.66 and 2.45
      times higher than within the normoxic epithelium, respectively. The length of
      calcitonin gene-related peptide-immunostained fibers within the chronically
      hypoxic olfactory and respiratory epithelium was 1.56 and 1.84 times higher,
      respectively. Because substance P and calcitonin gene-related peptide are the
      predominant signal peptides of primary sensory neurons, the increased number of
      these fibers may represent enhanced sensory mechanisms in the hypoxic nasal
      mucosa. In addition, considered together with the findings in chronically hypoxic
      tracheal mucosa, the increased density of intraepithelial fibers containing
      substance P and calcitonin gene-related peptide suggests that this is a
      predominant feature of hypoxic adaptation throughout the upper and lower
      respiratory tracts.

PMID- 9566500
TI  - Expression of Fos in the spinal motoneurons labelled by horseradish peroxidase
      following middle cerebral artery occlusion in rat.
AB  - The study was aimed at the investigation of the rat corticospinal system both
      functionally and anatomically using as a functional marker the immediate early
      gene c-fos, combined with retrograde tracing with horseradish peroxidase (HRP).
      This was achieved by mapping c-fos induction immunocytochemically in the spinal
      cord as a result of occlusion of the middle cerebral artery (MCA). Following left
      sided MCA occlusion, Fos-like immunoreactivity (Fos-LI) was localized in both the
      dorsal and ventral horn neurons at the lumbar segment of the spinal cord.
      Labelling was often bilateral but was generally more substantial ipsilaterally.
      In the ventral horn, some of the Fos-positive neurons were confirmed to be
      somatic motoneurons innervating the tibialis anterior muscle of the lower
      extremity contralateral to MCA occlusion, as shown by their retrograde labelling
      with horseradish peroxidase injected into the muscle. Fos-LI was absent in the
      ventral horn of the spinal cord at cervical, thoracic, and sacral segments in
      both experimental and sham-operated rats. These findings suggest that the
      expression of c-fos may be used as a sensitive transneuronal marker for the study
      of neuronal activity in the spinal cord elicited by brain damage, viz. focal
      cerebral ischaemia, and when coupled with injection of HRP as a retrograde
      tracer, the method may prove to be useful for the study of transneuronal effect
      of the damage of the corticospinal motor system. While the expression of c-fos in
      the spinal motoneurons was most probably attributable to transneuronal effect
      following MCA occlusion, the possibility of that c-fos can be induced by altered
      hindlimb activity after the cerebral ischaemic insult cannot be excluded.

PMID- 9566501
TI  - Cognitive changes in mice following moderate MPTP exposure.
AB  - We evaluated the cognitive effects of two moderate doses (30 mg/kg x 3 every 12 h
      and 20 mg/kg x 6 every 8 h, i.p.) of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine
      (MPTP) in mice. The dose of 30 mg/kg x 3 caused about 60% depletion of striatal
      dopamine but did not reduce the levels of its metabolites. Mice treated with MPTP
      did not differ from controls in their motor behavior in the open field. Mice
      treated with MPTP were comparable to controls in T-maze delayed alternation with
      fixed delays but were impaired when trials with mixed 20 s and 120 s delays were
      presented, indicative of a spatial working memory impairment. Dexmedetomidine at
      10 microg/kg (s.c.) slightly improved delayed alternation performance in all
      groups but also slowed initiation of the motor response. Mice treated with MPTP
      at the dose of 30 mg/kg x 3 were less sensitive to this adverse effect of
      dexmedetomidine. The impairment in spatial working memory after MPTP exposure in
      mice parallels the findings in monkeys, but the deficit is much less severe.

PMID- 9566502
TI  - Further characterization of forebrain serotonin receptors mediating tachycardia
      in conscious rats.
AB  - It has been shown recently that activation of forebrain serotonin1A (5-HT1A)
      receptors, likely within the preoptic area, elicits a slight increase in blood
      pressure and a substantial tachycardia. The present studies were designed to
      characterize: (1) the requirement of the 5-HT1A receptor agonist R(+)-8-hydroxy-2
      (di-n-propylamino) tetralin [R(+)8-OH-DPAT]-induced tachycardia on the integrity
      of serotonergic innervation of the preoptic area, (2) the ability of the 5-HT1A
      receptor partial agonist buspirone to elicit cardiovascular responses when
      microinjected into the preoptic area, (3) the role of 5-HT2 and 5-HT3 receptors
      in the preoptic area in cardiovascular regulation, and (4) the site specificity
      of the tachycardia produced by R(+)8-OH-DPAT. The data suggest that activation of
      5-HT1A receptors, but not 5-HT2 or 5-HT3 receptors, within or very near the
      preoptic area increases blood pressure and heart rate in conscious rats.
      Furthermore, the full response is dependent on afferent serotonergic innervation,
      suggesting a presynaptic modulatory role for 5-HT in the preoptic area.

PMID- 9566503
TI  - A kinetic model on calcium residues and facilitation.
AB  - The role of calcium as a regulator for neuronal function is very important.
      Calcium initiates many reactions that determine the behavior of the neuronal
      cell. In this article we use a kinetic model of the presynaptic synapsin I
      protein. This protein is responsible, via phosphorylation, for regulating the
      amount of transmitter vesicles available for release. This protein has been shown
      to inhibit the amount of vesicles ready for release in its dephosphorylated
      state, and releases its inhibitory binding due to phosphorylation. The
      phosphorylation of synapsin I depends on cyclic adenosine monophosphate and type
      II calcium/calmodulin protein kinase. Due to the duration of these two second
      messengers, we show that short-term facilitation does not have to depend on
      calcium residues. Furthermore, we show that calcium residues (in parts of microM
      range) promote increased facilitation due to the additional calcium reacting with
      the second messenger system.

PMID- 9566504
TI  - Time-dependent changes in neurotrophic factor mRNA expression after kindling and
      long-term potentiation in rats.
AB  - We compared the time-dependent changes in messenger ribonucleic acid (mRNA)
      levels for two neurotrophic factors after amygdala-kindled seizures and
      hippocampal long-term potentiation (LTP) in rats in vivo. The brain-derived
      neurotrophic factor (BDNF) mRNA levels in the bilateral granule cell layer of the
      dentate gyrus, increased significantly 1-4 h after stage 5 kindled seizures.
      Nerve growth factor (NGF) mRNA levels increased throughout the bilateral limbic
      regions more gradually than those of BDNF mRNA. The maximum levels in the dentate
      gyrus ipsilateral to stimulation (BDNF mRNA: 493%, NGF mRNA: 199% of control
      levels) occurred 2 h after seizures. As observed with kindling, BDNF and NGF mRNA
      expression increased in the dentate gyrus ipsilateral to stimulation also
      increased following LTP induced by the perforant path stimulation, with maximum
      levels occurring 2 h and 4 h, respectively, after stimulation, when they reached
      284% and 189% of the control levels, respectively. These results suggest that
      BDNF and NGF are involved in enhancement of synaptic efficacy in the granule
      cells of the dentate gyrus in the hippocampus in kindling, not related to the
      neuronal excitability associated with seizure activity.

PMID- 9566506
TI  - Neurotoxicity of 25-OH-cholesterol on sympathetic neurons.
AB  - Cultured rat sympathetic neurons derived from postnatal rat superior cervical
      ganglia (SCG) were used to compare the neurotoxicity of several cholesterol
      oxides. The cholesterol oxides tested included: 7-beta-OH-, 7-keto-, 19-OH-,
      22(R)-OH-, 22(S)-OH-, and 25-OH-cholesterol. These agents caused an acute as well
      as a delayed toxicity in sympathetic neurons with 25-OH-cholesterol appearing to
      be the most toxic. A time-dependent experiment indicated that 25-OH-cholesterol
      at 4 microg/ml (10 microM) was able to kill 50% of the cells in 36 h.
      Morphological studies indicate that most of the cells do not exhibit a structural
      change similar to that observed in neuronal programmed cell death. Whole-cell
      patch clamp recording of untreated controls and 25-OH-cholesterol (2 microg/ml)
      treated cells indicated that this toxicity was not accompanied by significant
      changes in voltage-dependent calcium channel activity. A number of
      pharmacological agents including ethylene glycolbis (beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid (EGTA), cycloheximide, KCl, vitamin E, and methyl-beta
      cyclodextrin were able to prevent the 25-OH-cholesterol-induced cell death to
      various degrees. These results suggest that, in addition to causing pathological
      changes in cells directly involved in atherosclerosis, cholesterol oxides may
      induce neurotoxicity in sympathetic neurons.

PMID- 9566505
TI  - Postsynaptic integration of cholinergic and dopaminergic signals on medium-sized
      GABAergic projection neurons in the neostriatum.
AB  - The effects of cholinergic drugs and the interaction between cholinergic and
      dopaminergic compounds were studied on electrically evoked [3H]gamma-aminobutyric
      acid (GABA) overflow in slices of the rat neostriatum. Slices were prepared and
      loaded with [3H]GABA in the presence of beta-alanine and then superfused with
      Krebs-bicarbonate buffer containing aminooxyacetic acid and nipecotic acid to
      inhibit GABA uptake and metabolism, respectively. The nonselective muscarinic
      agonist oxotremorine (0.1-10 microM) increased the release of [3H]GABA and the
      selective M1 receptor agonist McN-A-343 (0.1-10 microM) exerted similar effect.
      The stimulatory effect of oxotremorine (10 microM) on [3H][GABA overflow was
      antagonized by the nonselective muscarinic antagonist atropine (1 microM) and the
      selective M1 receptor antagonist pirenzepine (0.1-1.0 microM). The M2 receptor
      antagonist methoctramine (1.0 microM) did not alter the stimulatory effect of
      oxotremorine. Of the muscarinic receptor antagonists atropine, pirenzepine, and
      methoctramine (1.0 microM) failed to affect [3H]GABA overflow. The M3 receptor
      antagonist p-F-HHSiD (1 microM) increased [3H]GABA overflow and p-F-HHSiD and
      oxotremorine were found to be additive in increasing this effect. The D2 dopamine
      receptor antagonist sulpiride (10 microM) increased the electrical stimulation
      induced [3H]GABA overflow, and this stimulation was counteracted by concomitant
      administration of atropine (1 microM). McN-A-343 and sulpiride also increased the
      KCl-induced [3H]GABA overflow from superfused neostriatal slices and tetrodotoxin
      (1 microM) did not affect these stimulations. These data indicate that the
      release of GABA in the neostriatum is under the control of M1 stimulatory and M3
      inhibitory muscarinic receptors. Dopamine, which exerts inhibition on GABA
      release via D2 receptors, may counteract the M1 facilitation, and M1 and D2
      receptors involved in the cholinergic-dopaminergic interaction may be located
      postsynaptically on medium-sized spiny GABAergic projection neurons.

PMID- 9566507
TI  - The globus pallidus sends axons to the thalamic reticular nucleus neurons
      projecting to the centromedian nucleus of the thalamus: a light and electron
      microscope study in the cat.
AB  - We examined whether light and electron microscopically projection fibers from the
      globus pallidus (GP) of the cat might terminate on neurons of the thalamic
      reticular nucleus (RT) sending axons to the centromedian thalamic nucleus (CM).
      In the first group of experiments, wheat germ agglutinin-conjugated horseradish
      peroxidase (WGA-HRP) was injected into the GP, and anterogradely labeled
      preterminal and terminal-like elements were seen in the anterior part of RT. At
      the anterior pole of RT, these labeled elements were localized in its lateral
      portion. In the second group of experiments, the retrograde labeling method with
      WGA-HRP was combined with the degeneration method using kainic acid. In each cat,
      lesion was placed stereotaxically in the GP by kainic acid injection, and WGA-HRP
      was then injected into the CM ipsilateral to the kainic acid injection. In the
      rostral part of RT, a considerable number of degenerated axon terminals deriving
      from GP were seen to establish synaptic contact with dendritic and somatic
      profiles, which were retrogradely labeled by WGA-HRP injections in CM. The
      results indicate that GP innervates directly RT nucleus neurons projecting to CM.

PMID- 9566508
TI  - Regulation of hippocampal theta activity by corticosterone: opposing functions of
      mineralocorticoid and glucocorticoid receptors.
AB  - Recently, we reported that intrahippocampal cholinergic blockade increased
      corticosterone (CORT) and adrenocorticotrophin (ACTH) secretion induced by
      restraint stress. These data suggested to us that CORT may modify hippocampal
      cholinergic function as part of the negative-feedback control of hypothalamic
      pituitary-adrenal (HPA) axis activity. Hippocampal cholinergic theta is a
      rhythmic, sinusoidal waveform that occurs in alert, immobile rats presented with
      threatening stimuli and is reliably expressed in urethanized rats. We reasoned
      that if hippocampal cholinergic systems regulate HPA axis activity, perhaps CORT
      acts to modulate theta activity. In the present study we have examined the
      effects of blocking mineralocorticoid receptors (MR) and glucocorticoid receptors
      (GR) on theta activity in urethane-anesthetized rats. Adult male, Lister hooded
      rats (n=15) were anesthetized with urethane, and a theta recording electrode was
      positioned in the hippocampus adjacent to an infusion cannula. A bipolar
      stimulating electrode was placed in the dorsomedial posterior hypothalamus (DMPH)
      to activate theta. Baseline recordings of DMPH-stimulated activity (0.1-0.5 mA)
      were obtained. Rats were then administered either the MR antagonist
      spironolactone or the GR antagonist RU 38486 (150 ng), and DMPH-stimulated
      activities were monitored for 45 min. Changes in theta frequency (Hz) and
      amplitude (mV; energy at peak theta frequency) were analyzed using analysis of
      variance (ANOVA) followed by Bonferroni t-tests. Neither drug affected
      hippocampal theta frequencies elicited by DMPH stimulation. However, GR blockade
      produced marked increases in theta amplitudes of approximately 100% above predrug
      levels. Alternatively, MR blockade produced exactly the opposite response, as
      amplitude values fell to approximately 50% of predrug levels. Hippocampal
      cholinergic theta activity is modulated by CORT acting through MR and GR, and the
      rapidity of the response suggests a nongenomic mechanism. These data raise the
      possibility that hippocampal cholinergic systems, and theta activity, are
      involved in CORT-mediated negative-feedback control of the HPA axis.

PMID- 9566510
TI  - Practical imaging in acute pancreatitis.
AB  - Pancreatitis may be acute or chronic, mild or severe. In patients with acute
      pancreatitis the optimal imaging test is dynamic intravenous and oral contrast
      enhanced computed tomography (CECT). Serial CECTs are useful to monitor disease
      progression and to assess intraabdominal complications in patients with severe
      acute pancreatitis. CECT is helpful in planning the approach (endoscopic
      transmural versus percutaneous) for pancreatic drainage. Computed tomography or
      ultrasound-guided aspiration of pancreatic collections is safe, sensitive, and
      specific and has become a routine procedure used to screen for infected necrosis.
      When pancreatic drainage is contemplated, magnetic resonance imaging is useful
      for identifying residual necrotic debris within the collection. Patients with
      mild acute pancreatitis usually require no cross-sectional imaging study other
      than ultrasound screening for gallstones, if gallstone pancreatitis is suspected
      clinically. In patients with chronic pancreatitis, screening for complications
      such as superimposed acute pancreatitis or development of pancreatic pseudocysts
      may be performed with CECT or ultrasound.

PMID- 9566509
TI  - The fatty acid composition of maternal diet affects the response to excitotoxic
      neural injury in neonatal rat pups.
AB  - Fatty acids and their derivatives play a role in the response to neural injury.
      The effects of prenatal and postnatal dietary fatty acid composition on
      excitotoxic neural injury were investigated in neonatal rat pups. Dams were fed
      during gestation and lactation a diet whose fat source was either corn oil or
      menhaden fish oil. On postnatal day 3, litters were culled to 10 per dam. On
      postnatal day 4, excitotoxic neural injury was induced by infusion of the
      glutamate analog N-methyl-DL-aspartate (NMA) into the left cerebral hemisphere.
      Three days later, pups were killed and brains were removed for histological and
      volume assessments. Levels of arachidonic acid were 2.3-fold higher in cerebrums
      of pups in the corn oil group than in the fish oil group. Left cerebral
      hemispheres among all pups were atrophic. Right cerebral hemispheres of pups in
      the corn oil group showed more histological evidence of edema, and had
      significantly higher volumes than pups in the fish oil group (66 vs. 42 mm2,
      p=0.007). These data suggest that the fatty acid composition of prenatal and/or
      postnatal diet can affect the neonatal response to excitotoxic neural injury.

PMID- 9566511
TI  - Endoscopic ultrasonography in pancreatic disease.
AB  - Endoscopic ultrasound has emerged as an important modality for management of
      pancreatic disease because of its ability to provide high frequency images of the
      pancreatic ducts and the parenchyma. Development of interventional techniques
      under endosonographic guidance has further advanced the potential use of this
      technique in pancreatic disorders. This paper shows and reviews the current
      knowledge on endoscopic ultrasound in pancreatic imaging.

PMID- 9566512
TI  - Pancreatic fluid collections: diagnosis and endoscopic management.
AB  - Pancreatitis may be acute or chronic, mild or severe. Acute necrotizing
      pancreatitis remains the most serious form of acute pancreatitis and accounts for
      the majority of complications. Although there is an established nomenclature for
      pancreatitis and pancreatic fluid collections, such as pancreatic pseudocysts, it
      is not widely understood or recognized by gastroenterologists. Because the
      management options for the treatment of pancreatic fluid collections continues to
      evolve with an increased use of endoscopic therapy, gastroenterologists will be
      increasingly called on to treat patients with pancreatitis and its complications.
      This article addresses and summarizes pancreatic fluid collections and their
      management, with an emphasis on endoscopic drainage.

PMID- 9566513
TI  - Pancreatic duct stenting in benign pancreatic disease.
AB  - The ability to place endoscopic stents into the pancreatic duct has led to a
      dramatic increase in stent therapy for benign pancreatic diseases, particularly
      chronic pancreatitis and pancreas divisum. The overall effectiveness of this
      therapy remains unknown. This article critically reviews the available literature
      with a focus on patient selection, efficacy, and risk. The risk of pancreatic
      duct stenting is only now beginning to be appreciated, and clinicians must
      understand not only the potential effectiveness of pancreatic duct stenting but
      also the magnitude of the potential risk when considering this therapy.

PMID- 9566514
TI  - The surgical management of chronic pancreatitis (ductal strictures).
AB  - Chronic pancreatitis is a lifelong illness for patients and a persistent medical
      challenge for the gastrointestinal physician. Most cases are induced by alcohol
      abuse. This leads to a process of recurrent injury, chronic fibrosis and
      subsequent pain, pancreatic ductal scarring, and dilatation. The surgical
      management of these associated complications as seen in the patient presented in
      this report will be discussed in the context of the current surgical literature.

PMID- 9566515
TI  - Thioredoxin peroxidases from Brugia malayi.
AB  - Parasite-derived antioxidant proteins have been implicated in playing an
      important role in protection against the oxygen radicals that are generated
      during aerobic metabolism and in defense against host immune cell attack. Here we
      report that filarial nematodes include the thioredoxin peroxidase/thiol-specific
      antioxidant (TPx/TSA) family of antioxidant proteins as part of their complex
      defense against radical-mediated damage. At the protein level, the TPx/TSA from
      Brugia malayi (Bm-TPx-1) was approximately 50% identical and approximately 60%
      similar to TPx/TSAs from mammals, amphibians and yeast. Bm-TPx-1 was also
      approximately 60% identical to putative TPx proteins from a related filarial
      nematode, Onchocerca volvulus, and from the free-living nematode Caenorhabditis
      elegans. That B. malayi may express multiple forms of molecules with TPx/TSA
      activity was indicated by the identification of a B. malayi gene encoding a
      second, distinct member of the TPx/TSA family (Bm-tpx-2). Bm-tpx-1 was found to
      be transcribed in all stages of the parasite present in the mammalian host and
      the 25 kDa translation product was present in all of the developmental stages
      studied. The results of immunohistochemical, immunofluorescent and
      immunoprecipitation studies showed Bm-TPx-1 to be localized in the cells of the
      hypodermis/lateral chord in adult parasites and not to be present at the surface
      or in excretory/secretory products. The distribution in the parasite suggests
      that Bm-TPx-1 may play its major role in countering radicals produced within
      cells. A recombinant form of Bm-TPx-1 was biologically active and capable of
      protecting DNA from oxygen radical-mediated damage. Thioredoxin peroxidases may
      prove to be a critical component in the parasite's defense against injury caused
      by oxygen radicals derived from endogenous and exogenous sources.

PMID- 9566516
TI  - Thioredoxin peroxidase from Onchocerca volvulus: a major hydrogen peroxide
      detoxifying enzyme in filarial parasites.
AB  - Random screening of an Onchocerca volvulus third-stage (L3) cDNA library
      identified a highly abundant cDNA encoding a newly discovered antioxidant enzyme,
      thioredoxin peroxidase (TPx), a member of the peroxidoxin superfamily. This TPx
      cDNA (Ov-tpx-2) encodes a polypeptide of 199 amino acid residues with a
      calculated molecular weight of 21,890 Da. The Ov-tpx-2 cDNA represents roughly
      2.5% of the total cDNAs from the L3 cDNA library. The gene was expressed in
      Escherichia coli and the protein product was shown to have antioxidant activity.
      Antiserum raised against Ov-TPX-2 recognized a native protein from extracts of
      both the L3 and adult-stages with a molecular weight of 22 kD. The localization
      and stage-specificity of Ov-TPX-2 protein was analyzed by immunocytochemistry and
      immunoelectron microscopy using monospecific antibodies. Expression was detected
      in late first-stage larvae during development in the vector and increased in
      intensity during differentiation to the infective L3-stage. The antigen was also
      detected in post-infective larvae and adult worms. In larvae, Ov-TPX-2 protein
      was predominantly localized to the hypodermis and cuticle, with additional sites
      in the hypodermal chords and multivesicular bodies. In adult worms, the primary
      sites of expression were the uterine epithelium and intestine, with additional
      labeling of the body wall and cuticle. Developing embryos and microfilariae in
      utero were bathed in Ov-TPX-2 protein discharged from epithelial cells. These
      results suggest that Ov-TPX-2 may protect the parasites from being damaged by
      host-generated oxidative stress and that Ov-TPX-2 protein provides the H2O2
      detoxifying activity predicted but not previously identified in filarial
      parasites. Its highly upregulated expression in infective larvae may aid in
      parasite establishment following transmission to the definitive host.

PMID- 9566518
TI  - GRA7, an excretory 29 kDa Toxoplasma gondii dense granule antigen released by
      infected host cells.
AB  - Monoclonal antibody (mAb) TxE2, reactive with Toxoplasma gondii excretory
      products, detects an acidic 29 kDa protein (p29) which, in 2D gel
      electrophoresis, exhibits a migration pattern distinct from those of the
      toxoplasmic excretory proteins described so far. The sequence of seven peptides
      from tryptic digestion of isolated p29 allowed the design of primers to obtain
      the coding DNA sequence. The full-length gene was amplified from genomic DNA of
      T. gondii strain BK and the sequence was identical with that of the corresponding
      cDNA, providing evidence for an intron-free gene structure. A single mRNA
      transcript of 1.3 kb was detected by Northern blot analysis. The deduced 236
      amino acid protein contains a putative N-terminal signal peptide, one site of
      potential N-linked glycosylation, and, close to the C-terminus, a further
      hydrophobic, putative transmembrane domain. With synthetic peptides spanning the
      sequence of p29, the epitope for mAb TxE2 was mapped adjacent to the putative
      signal sequence. The antigen, which represents almost 0.5% of T. gondii protein,
      is expressed in strains of all three intraspecies subgroups, and is associated
      with the parasite dense granules as demonstrated by immunoelectron microscopy. In
      tachyzoite-infected cells, p29 accumulates within the parasitophorous vacuole and
      co-localizes with its delimiting membrane. In bradyzoite-infected cells, p29 is
      present within the host cell cytoplasm as detected by immunofluorescence
      staining, and, furthermore, in the supernatant of cyst-bearing cell culture
      lacking extracellular parasites as shown by enzyme-linked immunosorbent assay
      (ELISA). Thus, p29 which is named dense granule protein (GRA)7 may indicate the
      presence of intracellular toxoplasma.

PMID- 9566517
TI  - Identification and heterologous expression of a new dense granule protein (GRA7)
      from Toxoplasma gondii.
AB  - Immunoscreening of an expression library constructed with Toxoplasma gondii
      tachyzoite mRNA with sera from toxoplasmosis-positive humans has led to the
      identification of a new parasite antigen. Sequence analysis of the gene encoding
      this antigen allowed the calculation of the theoretical molecular mass (25,857
      Da) and showed that the protein contains a putative signal sequence. The C
      terminal region contains two hydrophobic regions, the last of which has the
      characteristics of a membrane-spanning domain. When the protein was
      heterologously expressed in E. coli and tested by Western blot, it reacted with
      the human sera originally used for screening. The new antigen also reacted with a
      monoclonal antibody raised against the entire parasite. Ultrastructural analysis
      showed that the protein is localized in the dense granules. After host cell
      invasion, the protein is secreted into the vacuolar network, the parasitophorous
      vacuole membrane, and into extensions protruding in the cytoplasm. Therefore, it
      is suggested to designate this new dense granule protein GRA7, following the
      established nomenclature for this protein family.

PMID- 9566519
TI  - Characterisation of a Trypanosoma cruzi acidic 30 kDa cysteine protease.
AB  - A novel proteolytic activity was identified in epimastigote, amastigote and
      trypomastigote forms of Trypanosoma cruzi using the fluorogenic substrate N
      Succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin. Epimastigotes showed enzyme
      activity to be 2-fold higher than amastigotes and trypomastigotes. The protease
      that displays this activity was purified from epimastigote forms by a four step
      chromatographic procedure: Diethylaminoethyl-Sephacel, Phenyl-Sepharose, Phenyl
      Superose, and Concanavalin A Sepharose columns. The purified enzyme is a
      glycoprotein that migrates as a 30 kDa protein in 12.5% SDS-polyacrylamide gel
      electrophoresis (PAGE), under reducing conditions. Its optimal enzymatic activity
      on both fluorogenic and protein substrates was found to occur at an acidic pH.
      The inhibition pattern of the purified 30 kDa protease showed that it belongs to
      the cysteine-protease class. In addition to the synthetic substrate, the purified
      protease hydrolysed bovine serum albumin (BSA) and human type I collagen. The N
      terminal amino acid sequence of the protease shows similarity to the mammalian
      cathepsin B protease.

PMID- 9566520
TI  - Identification of peripheral membrane proteins associated with the tubo-vesicular
      network of Plasmodium falciparum infected erythrocytes.
AB  - During intracellular development of the malarial parasite numerous membranous
      vesicles appear in the infected erythrocyte cytoplasm between the parasitophorous
      vacuolar membrane (PVM) and the erythrocyte plasma membrane. In this study we
      describe the characterization of a monoclonal antibody which recognizes two major
      parasite-encoded proteins of 50 and 41 kDa. Immunofluorescence and immunoelectron
      microscopy demonstrated that the monoclonal antibody reacts with cytoplasmic
      vesicles of Plasmodium falciparum infected erythrocyte referred to as Maurer's
      clefts. The antigens recognized by the monoclonal antibody were expressed very
      early during the erythrocytic life cycle of the parasite, and remained tightly
      associated within membrane vesicles even after merozoites are released from
      infected erythrocytes. The antigens were partially soluble in non-ionic
      detergents, and were released from the membrane by alkali treatment, indicating
      that the proteins recognized by the monoclonal antibody are peripheral membrane
      proteins. It is proposed that the 50 and 41 kDa antigens might be part of an
      underlying membrane skeletal network that provides structural support to vesicles
      and tubules present in the infected erythrocyte cytoplasm.

PMID- 9566521
TI  - Stage-specific expression of the 14-3-3 gene in Echinococcus multilocularis.
AB  - A cDNA expression library representing the metacestode developmental stage of the
      tapeworm Echinococcus multilocularis was immunoscreened with monospecific
      antibodies affinity purified following differential immunoblot analysis. Using
      this procedure, a metacestode-specific clone was isolated representing a 14-3-3
      gene of the parasite, which is present as a single copy in the parasite genome.
      The identity of this clone was demonstrated by cross-reactivity of the
      recombinant E. multilocularis 14-3-3 protein with antibodies raised against a
      heterologous 14-3-3 protein from Saccharomyces cerevisiae. In addition,
      expression of the E. multilocularis 14-3-3 gene in the mutant S. cerevisiae
      strain, DS9-22, resulted in complementation of the phenotypic deficiency of this
      strain, thus demonstrating the functionality of the respective gene product. By
      reverse transcription-polymerase chain reaction (RT-PCR) we showed that the E.
      multilocularis 14-3-3 protein is about 10-fold overexpressed in the metacestode
      stage compared with the expression level in the adult stage. Immunolocalization
      of the 14-3-3 protein in E. multilocularis metacestodes revealed its predominant
      presence in the germinal layer of the parasite. The results of this study, taken
      together with the current knowledge on the 14-3-3 protein family, suggest that
      this parasite molecule may contribute to the promotion of the progressive,
      potentially unlimited growth behaviour of the E. multilocularis metacestode
      within the host tissue.

PMID- 9566522
TI  - Gene knock-outs and allelic replacements in Toxoplasma gondii: HXGPRT as a
      selectable marker for hit-and-run mutagenesis.
AB  - The hypoxanthine-xanthine-guanine phosphoribosyl transferase (HXGPRT) gene of the
      protozoan parasite Toxoplasma gondii encodes a safe, practical genetic marker
      suitable for both positive and negative selection. Taking advantage of the
      ability to control homologous versus nonhomologous recombination in haploid T.
      gondii tachyzoites by manipulating the length of homologous DNA sequence, we have
      explored the possibility of 'hit-and-run' mutagenesis to introduce gene knock
      outs (or allelic replacements) at loci for which no known selection or screen is
      available. Using the uracil phosphoribosyl transferase (UPRT) locus as a target,
      a genomic clone containing approximately 8 kb encompassing the UPRT gene (but
      lacking essential coding sequence) was fused to a cDNA-derived HXGPRT 'minigene',
      which lacks sufficient contiguous genomic sequence for homologous recombination.
      After transfection of circular plasmid DNA, positive selection for HXGPRT
      activity identified stable transformants, > 30% of which were found to have
      integrated at the UPRT locus as 'pseudodiploids' (produced by single-site
      homologous recombination between the circular plasmid and genomic DNA). Upon
      removal of mycophenolic acid, resolution of pseudodiploids by spontaneous
      intrachromosomal homologous recombination was selected using 6-thioxanthine,
      yielding a 1:1 ratio of UPRT knock-out parasites to wild-type revertants, at
      frequencies of approximately 10(-6) per parasite doubling. Applications of 'hit
      and-run' technology relative to other gene targeting strategies are discussed.

PMID- 9566523
TI  - Developmental and tissue-specific expression of 2-methyl branched-chain enoyl CoA
      reductase isoforms in the parasitic nematode, Ascaris suum.
AB  - The 2-methyl branched-chain enoyl CoA reductase (ECR) plays a pivotal role in the
      reversal of beta-oxidation operating in anaerobic mitochondria of the parasitic
      nematode, Ascaris suum. Two-dimensional gel electrophoresis of the purified ECR
      yielded multiple spots, with two distinct but overlapping N-terminal sequences.
      These multiple isoforms were not the result of population effects, as the pattern
      observed on 2-D gels of the purified ECR was identical to those on immunoblots of
      muscle homogenates isolated from individual worms. A full-length cDNA coding for
      the major ECR isoform (ECRI) has been cloned and sequenced and compared with that
      of the minor isoform (ECRII) which has been described previously (Duran et al. J
      Biol Chem 1993;268:22391-22396). ECRI contained the 22-nucleotide trans-spliced
      leader sequence characteristic of many nematode mRNAs, a 5' untranslated region
      (UTR) of 13 nucleotides, an open reading frame (ORF) of 1257 nucleotides, a 3'
      UTR of 110 nucleotides that included the polyadenylation signal AATAAA downstream
      of the termination codon and a short poly(A) tail. The ORF predicted a 16 amino
      acid leader sequence not found in the native protein and a mature protein of 403
      amino acids with a molecular weight of 43 698 and a predicted pI of 6.2. ECRI and
      ECRII were 73% identical at the predicted amino acid level and their mRNAs
      exhibited significant structural similarity even though they were products of
      separate genes. Comparison of ECRI and ECRII with the sequences of acyl CoA
      dehydrogenases from a variety of different sources revealed a high degree of
      interspecies sequence identity, suggesting that these enzymes may have evolved
      from a common ancestral gene. This result is surprising since the ascarid enzymes
      function as reductases, not as dehydrogenases. Both ECRs were tissue-specific and
      developmentally regulated and were found in transitional third-stage larvae (L3)
      and adult muscle, but not in early, aerobic larval stages or adult testis, ovary,
      or intestine. The ratio of ECRII to ECRI was greater in L3 than in adult muscle.
      Interestingly, both ECRs also appeared to be expressed in pharyngeal muscle,
      suggesting that branched-chain fatty acid synthesis may not be confined
      exclusively to body wall muscle.

PMID- 9566524
TI  - The DnaJ family of protein chaperones in Trypanosoma cruzi.
AB  - We have molecularly cloned four members of the DnaJ (heat shock protein 40)
      family of protein chaperones of the protozoan parasite Trypanosoma cruzi--tcj1,
      tcj2, tcj3 and tcj4. While all the proteins contain defining J domains at their N
      termini, only tcj2, tcj3 and tcj4 contain glycine/phenylalanine-rich and zinc
      finger domains common to many other DnaJ homologues. Furthermore, tcj2 and tcj4
      contain C-terminal CaaX motifs, substrates for prenyl modifications, suggesting
      that they are associated with cellular membranes. tcj1 is a divergent member of
      the family, containing neither glycine/phenylalanine-rich nor zinc finger
      domains. All the T. cruzi DnaJ genes are single copy, in contrast to other T.
      cruzi heat shock genes, which are arranged in multicopy direct tandem arrays.
      Among the tcj mRNAs, only tcj2 is heat inducible, which may result from
      posttranscriptional regulation involving a sequence found in the 3' untranslated
      regions of all heat-inducible T. cruzi mRNAs described to date. Further study of
      this important family of protein chaperones will aid our understanding of the
      protein folding and assembly processes in protozoans.

PMID- 9566525
TI  - Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein
      homolog.
AB  - Resistance to ivermectin and related drugs is an increasing problem for parasite
      control. The mechanism of ivermectin resistance in nematode parasites is
      currently unknown. Some P-glycoproteins and multidrug resistance proteins have
      been found to act as membrane transporters which pump drugs from the cell. A
      disruption of the mdrla gene, which encodes a P-glycoprotein in mice, results in
      hypersensitivity to ivermectin. Genes encoding members of the P-glycoprotein
      family are known to exist in nematodes but the involvement of P-glycoprotein in
      nematode ivermectin-resistance has not been described. Our data suggest that a P
      glycoprotein may play a role in ivermectin resistance in the sheep nematode
      parasite Haemonchus contortus. A full length P-glycoprotein cDNA from H.
      contortus has been cloned and sequenced. Analysis of the sequence showed 61-65%
      homology to other P-glycoprotein/multidrug resistant protein sequences, such as
      mice, human and Caenorhabditis elegans. Expression of P-glycoprotein mRNA was
      higher in ivermectin-selected than unselected strains of H. contortus. An
      alteration in the restriction pattern was also found for the genomic locus of P
      glycoprotein derived from ivermectin-selected strains of H. contortus compared
      with unselected strains. P-glycoprotein gene structure and/or its transcription
      are altered in ivermectin-selected H. contortus. The multidrug resistance
      reversing agent, verapamil, increased the efficacy of ivermectin and moxidectin
      against a moxidectin-selected strain of this nematode in jirds (Meriones
      unguiculatus). These data indicate that a P-glycoprotein may be involved in
      resistance to ivermectin and other macrocyclic lactones in H. contortus.

PMID- 9566526
TI  - Cloning, expression and characterization of a new filarial cyclophilin.

PMID- 9566527
TI  - Cloning and characterization of the kinetoplastid membrane protein-11 gene locus
      of Trypanosoma brucei.

PMID- 9566528
TI  - 3D topography of noncompact zone Golgi tubules in rat spermatids: a computer
      assisted serial section reconstruction study.
AB  - BACKGROUND: In the Golgi apparatus, the 3D topography of saccules in the compact
      zones (CZs) is better understood than that of tubules in the noncompact zones
      (NCZs). The positioning of NCZ tubules relative to each other and to CZ saccules
      was studied in rat spermatids by computer-assisted serial section microscopy.
      METHODS: Twenty-four (semi) serials (3-6 consecutive sections each) in total were
      collected from untreated tissues and from tissues treated for glucose-6
      phosphatase (G6P) cytochemistry as an alignment tool. The serials proceeded along
      either the cis-trans or the medial-lateral axes of the Golgi and collectively
      sampled all portions of this organelle. Selected serials were computer
      reconstructed and the final models displayed in red-green/red-blue stereo.
      RESULTS: In single thin sections, NCZ tubules typically appeared randomly
      oriented; however, in serial sections a high degree of organization was evident.
      Most tubules were traceable to the type of tubular networks (TNs) that
      interconnect equivalent CZ saccules (see review Rambourg and Clermont, 1990) Such
      TNs were present at consecutive saccular levels through each NCZ, were stacked
      like the saccules from which they originate, and in many regions were aligned
      from cis-trans. The cis-most of the TNs projected above the cis-pole of the
      stacked saccules and were penetrated by coated and uncoated ER buds. CONCLUSIONS:
      The function of the extensive NCZ tubular domain, consisting of the stacked and
      aligned TNs, will have to be addressed in future studies. However, the specific
      topography of the cis-most TNs make them candidates to serve as acceptor
      membranes in ER-Golgi transport.

PMID- 9566529
TI  - Degradation and repair of elastic fibers in rat lung interstitial fibroblast
      cultures.
AB  - BACKGROUND: Evidence from in vitro and in vivo studies indicates that damaged
      elastic fibers can be repaired. METHODS: Lipid interstitial pulmonary fibroblasts
      were cultured for 6 weeks. Cultures were then exposed to 25 microg of porcine
      pancreatic elastase and fixed in pairs (control, elastase-treated) immediately
      after exposure and at 1, 2, 3, 4, 7, 10, 14, and 22 days for ultrastructural
      examination. Elastin was also analyzed biochemically for resistance to hot
      alkali, an indicator of repair. Steady-state levels of tropoelastin and lysyl
      oxidase mRNA at 2, 4, and 7 days after elastase treatment were determined by
      Northern blot analysis. RESULTS: Immediately after exposure to elastase, damaged
      elastic fibers exhibited a frayed, porous appearance and a granular texture.
      Through day 4, fibers showed no evidence of repair. By day 7, the granular
      texture of damaged fibers was no longer evident and a gradual filling-in of
      porous areas appeared to be taking place. By 22 days, elastic fibers were
      indistinguishable from elastic fibers in control cultures. The ultrastructural
      changes were paralleled by changes in hot alkali resistance. Through day 4, there
      was no change in the level of hot alkali resistant elastin. Between day 4 and day
      7, resistance to hot alkali increased sharply and continued to increase at a
      slower rate, reaching 84% of the control level by day 22. Steady-state levels of
      tropoelastin and lysyl oxidase mRNA showed no increase over control levels at 2,
      4, and 7 days after elastase treatment. CONCLUSIONS: Elastic fibers synthesized
      by lipid interstitial pulmonary fibroblasts in culture were repaired after damage
      by elastase. This type of repair may have relevance to the prevention of
      pathological conditions, such as emphysema.

PMID- 9566530
TI  - Comparison of biomechanical properties of the incisor periodontal ligament among
      different species.
AB  - BACKGROUND: The aim of this study was to obtain a more precise understanding of
      the mechanical properties of the periodontal ligament in continuously erupting
      incisors by comparing the shear stress-strain relations among teeth from four
      closely related species. METHODS: Four species of experimental animals (mice,
      hamsters, rats, and rabbits) were used. Transverse sections of the left
      mandibular incisors were cut from the incisal, middle, and basal regions of each
      incisor. The tooth was pushed out of the alveolar bone in an extrusive direction
      at 5 mm/min using a materials testing machine. The maximum shear stress, maximum
      shear strain, tangent modulus, and failure strain energy density were estimated
      from the resulting stress-strain curve. Polarized light microscopic observations
      of collagen fibers were also made. RESULTS: All the biomechanical measures tended
      to decrease from the incisal toward the basal regions in all species. There were
      large species differences, especially in the incisal region, with the greatest
      maximum shear stress and failure strain energy density in hamsters. The greatest
      tangent modulus and the smallest maximum shear strain were observed in mice. The
      birefringent fiber architectures of the periodontal ligaments in the four species
      appeared to be similarly organized; the incisal periodontal ligament appeared to
      have more organized and thicker collagen fibres than did the middle and basal
      ligaments in the four species. CONCLUSIONS: These results suggest that the
      regional differences in the biomechanical properties of the periodontal ligament
      depend upon the developmental stages of the periodontal collagen fibers that may
      be related to the general arrangement, diameters, and densities of the collagen
      fiber bundles and the fiber insertions into the alveolar bone and cementum. The
      species differences in the biomechanical properties may be due to differences in
      the width of the periodontal ligament and the waviness as well as the strength
      and stiffness of the periodontal collagen fibers.

PMID- 9566531
TI  - Chondrocyte apoptosis increases with age in the articular cartilage of adult
      animals.
AB  - BACKGROUND: Apoptosis in vivo has been identified in developing cartilage from
      embryonic chick sterna and avian and murine growth plates. To date, no evidence
      exists that chondrocytes in articular cartilage undergo apoptosis. METHODS: We
      examined the distribution of cells demonstrating fragmented DNA in the articular
      knee cartilage of C57BL/6 mice (aged 11, 18, 24, and 30 months) and Wistar rats
      (aged 6, 12, and 24 months) using a DNA end-labeling technique. RESULTS: Control
      experiments utilizing retinoic acid-induced apoptosis in a chondrocyte cell line,
      established that DNA end-labeling correlated with DNA ladder formation. In vivo,
      apoptotic cells were detected in articular cartilage tissue in both species
      examined. The percentage of apoptotic cells increased significantly (P < 0.05
      with age) for all joint surfaces in both species. No significant difference was
      found between the medial and lateral or femoral and tibial joint surfaces of the
      knee. Apoptotic cells were observed in both the calcified and uncalcified regions
      of the articular cartilage of C57 mice. In the rat, only the calcified region of
      articular cartilage contained apoptotic cells. CONCLUSIONS: These results suggest
      that apoptosis plays a role in some aspect of maintenance, remodeling, or
      turnover of mature articular cartilage. In addition, the increase in apoptosis
      associated with aging could contribute to the greater risk for cartilage
      degeneration.

PMID- 9566532
TI  - Effect of intramuscular sulfadoxine-pyrimethamine on pregnant Wistar rats.
AB  - BACKGROUND: Sulfadoxine-pyrimethamine preparations are used commonly for the
      treatment and or prevention of malaria in the endemic regions of Sub-Sahara
      Africa. Pyrimethamine alone has been shown to be teratogenic in rats, mice and
      hamsters, and others animals. METHODS: Pregnant Wistar rats were divided into
      three groups. The first group received a therapeutic dose of sulfadoxine
      pyrimethamine (0.72 mg/kg body weight) intramuscularly (1.m) on the 5th, 12th,
      and 19th of gestation (3 doses). The second group received a similar dose on the
      10th and 17th days of gestation (2 doses); the third group received the same dose
      on the 15th and 22nd days of gestation (2 doses). Controls for each group
      received 2 ml of physiological saline through the same route on similar days
      instead of the drugs. RESULTS: All control animals produced normal litters
      (average 5.6), but group 3a animals produced litters with no obvious congenital
      malformations (average 4.8). Animals in groups 1a and 2a produced no litters.
      When they were sacrificed, they showed implantation sites in their uterine horns.
      Histological sections of these implantation sites showed that the embryos had
      been resorbed. CONCLUSIONS: Therapeutic dose of sulfadoxine-pyrimethamine (0.72
      mg/kg body weight) administered early in gestation resulted in complete embryo
      resorption in Wistar rats. The use of these preparations in early pregnancy in
      man demands caution.

PMID- 9566533
TI  - Morphology of sites of adhesion between hepatic stellate cells (vitamin A-storing
      cells) and a three-dimensional extracellular matrix.
AB  - BACKGROUND: Hepatic stellate cells lie in the perisinusoidal space in a three
      dimensionally distributed extracellular matrix (ECM). This three-dimensional
      structure of the ECM regulates the proliferation, morphology, and functions of
      the stellate cell. To investigate how the three-dimensional structure of ECM
      regulates behavior of the cells, we cultured stellate cells two- or three
      dimensionally and examined the morphology of the cells in both cases as well as
      the localization of cell-surface adhesion molecules specific for the ECM.
      METHODS: Isolated rat stellate cells and human stellate cells were cultured in
      Dulbecco's modified Eagle's medium. Rat stellate cells were cultured in non
      coated polystyrene culture dishes, or on or in type I collagen gels. The
      morphology of cell-ECM adhesion was examined under transmission and scanning
      electron microscopes. Localization of integrin alpha2 and integrin beta1 in human
      stellate cells was examined by immunoelectron microscopy. Immunostaining was
      performed with a mouse monoclonal anti-human integrin alpha2 or integrin beta1
      antibody and goat anti-mouse IgG coupled with 10-nm immunogold. RESULTS: Hepatic
      stellate cells cultured in polystyrene dishes spread well. However, the cells
      cultured on or in the type I collagen gel became slender. The cells extended long
      cellular processes onto or into the gel. The cellular processes were entangled
      three-dimensionally with the type I collagen fibers and directly adhered to these
      fibers. The cells inoculated in type I collagen gels formed a large number of
      adhesive structures that resembled focal adhesions. These adhesive structures
      were distributed not only on the lower side but also on the upper side of both
      the cell bodies and cellular processes. Moreover, each adhesive area formed a
      face but not a point. Integrin alpha2 and integrin beta1 were detected on the
      surfaces of cell bodies, cellular processes, and microprojections. CONCLUSIONS:
      The cells cultured in type I collagen gel develop a three-dimensional adhesive
      structure.

PMID- 9566534
TI  - Morphological and quantitative study of the intrinsic nerve plexuses of the
      canine trachea as revealed by immunohistochemical staining of protein gene
      product 9.5.
AB  - BACKGROUND: The ganglionated nervous plexuses in the trachea play an important
      role in the regulation of respiration. Although the tracheal tissue of the dog
      has frequently been used in physiological and pharmacological studies, little is
      known about the morphology of the intrinsic nervous plexuses in the dog trachea
      and quantitative data about the ganglia and nerve cell bodies are lacking. The
      structure of the nervous plexuses and detailed morphometric data about the
      intrinsic neurons of the dog have not previously been reported. METHODS: The
      structure of the intrinsic nerves in the dog trachea was examined by a
      combination method of digestion with KOH and immunohistochemical attaining of
      protein gene product 9.5. In addition, areas of nerve cell profiles, numbers of
      nerve cell bodies per ganglion and densities of nerve cell bodies per ganglion
      were estimated in preparations from five dogs. RESULTS: In the dog trachea, the
      peritracheal plexus, outer submucosal plexus, inner submucosal plexus, and
      mucosal plexus were identified from adventitia to epithelium in that order. The
      peritracheal plexus, situated in the lamina adventitia of the trachea, consisted
      of thick nerve bundles that were densely distributed in the membranous wall. The
      peritracheal plexus contained ganglia with round or oval nerve cell bodies. In
      the trachealis muscle, the intramuscular plexus, which was a well-developed,
      three-dimensional nervous network, was observed. It did not include ganglia and
      consisted of inter- and intrafascicular networks. The outer submucosal plexus was
      observed as small clusters in the inside of the trachealis muscle. A few round
      nerve cells were observed in the outer submucosal plexus as small clusters. The
      ganglionated inner submucosal plexus was identified in the superficial layer of
      the submucosal layer. A finer meshwork, namely, the mucosal plexus, was observed
      in the lamina propria. Among the entire length of the trachea, we counted 2,134
      2,873 ganglia (average, 2,389) and 13,902-24,232 nerve cell bodies
      (average,18,461) were counted in the peritracheal plexuses of five dogs. The
      densities of ganglia and nerve cell bodies were high near the carina and low near
      the thoracic inlet. The number of nerve cell bodies per ganglion was estimated as
      6.5-8.8 (average, 7.7). The average maximum area of nerve cell profiles was 522
      +/- 223 microm2. CONCLUSIONS: The structure of the tracheal plexuses in the dog
      is more complex than those in other smaller animals. The constitution of the
      plexuses seems to be that of the intestine. The numerous nerve cells in the
      peritracheal plexus in the adventitia can be expected to play important roles in
      airway regulation and in the pathogenesis of tracheal collapse.

PMID- 9566535
TI  - Gonadotropic and thyrotropic cells from the Mediterranean yellowtail (Seriola
      dumerilii; Risso, 1810): immunocytochemical and ultrastructural characterization.
AB  - BACKGROUND: Gonadotropins GTH I and GTH II from the pituitary of Mediterranean
      (M.) yellowtail (Seriola dumerilii) were isolated and characterized, and antisera
      to the whole GTH II molecule (anti-My alpha,betaGTH II) and to its beta-subunit
      (anti-My betaGTH II) were obtained. At the light microscopic level, anti-My
      alpha,betaGTH II reacted with My betaGTH II-immunoreactive cells (GTH II cells),
      thyroid-stimulating hormone (TSH) cells, and a third cell population, which could
      have been GTH I cells. The aim of this study was the ultrastructural
      characterization of GTH and TSH cells in M. yellowtail using the immunogold
      method in order to provide a basis for future research into reproduction of this
      species. METHODS: Pituitaries from mature male and female specimens reared in
      captivity were dissected out and processed for electron microscopy. The
      immunogold method was carried out by using anti-My alpha,betaGTH II, anti-My
      alpha,betaGTH II preabsorbed with the alpha subunit of the M. yellowtail GTH (My
      alphaGTH-subunit), anti-My betaGTH II, anti-human (h) alpha,betaTSH, and anti-h
      betaTSH sera to reveal gonadotropic and thyrotropic cells. RESULTS: M. yellowtail
      gonadotropic cells were very heterogeneous with regard to their size, shape, and
      ultrastructural features. Cells were found with numerous, round, variably
      electron-dense, secretory granules and globules; others were found with their
      cytoplasm occupied mostly by dilated cisternae of rough endoplasmic reticulum
      (RER) and scarce secretory granules; and other intermediate cell forms were found
      that showed varying proportions of secretory granules and dilated RER. The
      secretory granules and globules were immunogold labeled with anti-My
      alpha,betaGTH II, and the reaction was weaker in the latter. A similar immunogold
      labeling pattern was found with anti-My betaGTH II and with anti-My alpha,betaGTH
      II preabsorbed with the My alphaGTH-subunit, although some cells that showed the
      same ultrastructural features described above were not immunogold labeled and
      could have been GTH I cells. Thyrotropic cells had small, round, secretory
      granules of medium or high electron density that were immunogold labeled with
      anti-My alpha,betaGTH II, anti-h alpha,betaTSH, and anti-h betaTSH sera, but not
      with anti-My betaGTH II or anti-My alpha,betaGTH II serum preabsorbed with the My
      alphaGTH-subunit. All of the cell forms described for gonadotropes and
      thyrotropes were also found in a state of involution. CONCLUSIONS: Gonadotropes
      that are of a single morphological type but that vary in ultrastructure are
      present in the pituitary of captive M. yellowtail. GTH II- and putative GTH I
      producing cells were distinguishable from one another and from TSH cells by their
      different reactions to anti-My alpha,betaGTH II, anti-My betaGTH II, and anti-My
      alpha,betaGTH II preabsorbed with the My alphaGTH-subunit.

PMID- 9566536
TI  - The development of the terminal end bud in the prepubertal-pubertal mouse mammary
      gland.
AB  - BACKGROUND: The mammary gland is one of the few organ systems in mammals that
      completes its morphologic development postnatally. Due to this unique
      developmental property, it serves as an excellent model for studying ductal
      morphogenesis beyond embryonic life. The primary objective of this study was to
      investigate the development of terminal end bud (TEB) structure in the
      prepubertal-pubertal mouse mammary gland. METHODS: Seventy-five mice, weaned at
      21 days of age, were fed a high fat, nonrestricted intake diet for optimum
      mammary gland growth. Whole-mount preparations and a computer-assisted image
      analyzer were used to record the size and number of TEB structures in the
      thoracic and inguinal mammary glands. Alight microscope was used to determine the
      number of cap cells present in select TEB structures. RESULTS: In the prepubertal
      age group, the size and number (No.) of TEBs in the No. 2 and No. 3 thoracic
      glands were significantly greater than those in the No. 4 inguinal gland. In the
      pubertal age group, the size and number of TEBs in the No. 2 gland significantly
      decreased, indicating that for this particular gland the largest size and
      greatest number of TEBs are present during the prepubertal growth period. In
      contrast, the size and number of TEBs in the No. 3 and No. 4 glands remained
      relatively constant throughout the prepubertal-pubertal growth period.
      CONCLUSIONS: The results of this study show: (1) like the rat mammary gland,
      there is asynchronous growth among the mouse mammary glands, (2) the maximum size
      and number of TEBs in the prepubertal-pubertal mouse mammary glands are a
      function of the gland of origin and the age of the mouse, and (3) the number of
      cap cells per TEB structure is directly correlated with the size of the TEB
      structure.

PMID- 9566537
TI  - A novel junction-like membrane complex in the optic nerve astrocyte of the
      Japanese macaque with a possible relation to a potassium ion channel.
AB  - BACKGROUND: A new type of junction-like membrane complex (JMC) was detected
      between adjacent astrocytes in the optic nerve of Japanese macaque (macaca
      fuscata). This membrane complex morphologically resembled a cell junction, but a
      possible role for potassium ion channels could not be denied based on freeze
      fracture replica observation. We attempted to determine the chemical nature and
      function of the novel JMC. METHODS: Using an electron microscope, we observed
      JMCs in the optic nerve astrocyte. In addition, we observed them using a freeze
      fracture replica and immunohistochemistry with connexin 43, a gap junction
      specific protein. Furthermore, immunolocalization of an inwardly rectifying
      potassium ion channel, K(AB)-2 (Kir4.1), was studied with a confocal laser
      scanning microscope, and an electron microscope using a newly developed pre
      embedding method. RESULTS: These JMCs were abundant around the blood vessel in
      the area just behind the lamina cribrosa. At JMCs the inner leaflet was thicker
      than the outer leaflet and electron-dense materials were packed in the
      intercellular space. Freeze-fracture replica observation revealed orthogonal
      arrays of particles, probably at the place of JMCs, that have been considered a
      potassium ion channel. No connexin 43 immunoreactivity was detected in JMCs,
      while K(AB)-2 was mostly localized on either side of the opposing cell membranes
      of JMC. CONCLUSIONS: These JMCs do not seem to be a simple junction, but relate
      to a potassium ion channel. The area just behind the lamina cribrosa may be
      important in terms of conductance of the optic nerve impulse.

PMID- 9566538
TI  - Biomechanical stability of abductor pollicis longus muscles with variable numbers
      of tendinous insertions.
AB  - BACKGROUND: In the course of a study of different variants of the tendon of the
      abductor pollicis longus (APL) muscle, the unusual finding of a tendon with six
      subdivisions was observed in the first compartment. Using this preparation and
      others with various numbers of tendons (2, 3, 4, and 6), we intended to establish
      whether the multitendoned muscles increased the strength of the thumb. METHODS:
      Fifty-two upper extremities were examined with attention to the tendons of the
      APL muscle. The strain on each tendon was biomechanically determined using a
      microcomputer and potentiometer. The stress was measured continuously and plotted
      against strain. RESULTS: Following treatment with elastase, it is seen that the
      significance of changes in stability and Young's modulus is inversely
      proportional to the number of tendons arising from the APL. CONCLUSIONS: Division
      of the tendon into several parts leads to better mechanical distribution of
      stress and extension on thumb abduction. In addition, palmar-flexion in the wrist
      may be supported.

PMID- 9566539
TI  - Facial volume changes during normal human growth and development.
AB  - BACKGROUND: To describe normal soft tissue growth and development of the human
      face through volume changes and to assess the presence of sexual dimorphism.
      METHODS: Facial landmark identifications (2,023) were performed on 1,347 healthy
      Caucasian children and adolescents, ages 6-18 yr, and young adults, ages 19-32
      yr. Three-dimensional coordinates of 22 facial landmarks were collected by
      automated infrared photogrammetry. Facial volumes and selected linear distances
      and ratios were calculated and averaged for age and sex. RESULTS: Whereas in
      females in the 14-15 age group, the face had almost completed its growth relative
      to the adult group, in males a large increase was still to occur, in general
      agreement with previous reports on craniofacial growth, which suggested a strong
      tendency in males for growth to continue for several years beyond that seen in
      females. The male vs. female comparison reflected the different growth patterns.
      On average, within each age group volumes were significantly larger in males than
      in females, with some exceptions in the 11-12 age group, where female growth
      velocity showed a spurt. Sexual dimorphism in facial volume did not appear in
      different parts of the face to the same extent: a large part of male facial
      volume preponderance occurred in the lower third of the face. CONCLUSIONS: From 6
      yr of age to adulthood, facial soft tissues increased their volumes by >40%, with
      different growth patterns in boys and girls.

PMID- 9566540
TI  - Simultaneous observation of capillary nets and tenascin in intestinal villi.
AB  - BACKGROUND: In order to reveal the biological role of capillaries in a tissue, it
      is desirable to study the three-dimensional distribution of capillary nets in
      relation to tissue architecture. However, the simultaneous observation of the
      three-dimensional distribution of these nets and other substances has been rarely
      performed to date. In the present study, we have developed a novel method for
      investigating the three-dimensional distribution of capillary nets simultaneously
      with that of extracellular matrix components, such as tenascin, using the
      confocal laser scanning microscope. METHODS: Adult male mice were perfused with
      TRITC-labelled gelatin. After perfusion, the intestine was irrigated with chilled
      fixative containing paraformaldehyde and picric acid, dissected, and returned to
      the same fixative. The intestine was further sectioned and indirectly
      immunostained for tenascin using an FITC-labelled antibody. RESULTS: The three
      dimensional distribution of capillary nets and tenascin in villi was
      simultaneously observed on stereo pairs of pseudo-colored and superimposed
      images. Tenascin was distributed at the basement membrane zone and in the
      underlying connective tissue but absent in some regions where capillary nets were
      running just beneath the epithelium. Substances other than tenascin also can be
      examined in correlation with capillary nets. CONCLUSIONS: This method will be
      useful for investigating the biological role of capillary nets.

PMID- 9566541
TI  - Improving methodologies for the treatment of child and adolescent disorders:
      introduction.
AB  - This special issue grew out of a workshop sponsored by the National Institute of
      Mental Health, the MacArthur Foundation, and the Child and Adolescent
      Psychosocial Interventions Consortium. The goals of the workshop are outlined.
      The contents of the special issue are then described: definitions of
      psychotherapy and its mechanisms of action, developmental issues in psychotherapy
      research, methodologies for the treatment of anxious youth, measurement of change
      in interventions, predicting the outcome of treatment, and advancing the efficacy
      and effectiveness of psychosocial treatments. Finally, some areas that need to be
      addressed in the future are discussed, such as process research, the effects of
      comorbidity on outcomes, intensity, and duration, and transferability of
      treatments.

PMID- 9566542
TI  - Methodological strategies in child clinical trials: advancing the efficacy and
      effectiveness of psychosocial treatments.
AB  - The present paper reviews issues of treatment efficacy (i.e., potency) and
      effectiveness (i.e., clinical utility) in applied clinical child research.
      Threats to treatment evaluation are reviewed in the context of these two
      dimensions. It is proposed that treatment outcome research faces new challenges
      stemming from the ever increasing emphasis on generalization of gains and
      dissemination of interventions outside of clinical research settings. Issues and
      approaches proposed as warranting further development and attention include
      development, flexibility, acceptability, and disseminability of psychosocial
      assessment and treatment methods. A research emphasis is promoted that balances
      experimental control with the need for treatment generalization and delivery
      outside of the research setting, in order to maximize the utility of clinical
      research.

PMID- 9566544
TI  - Methodological issues in treatment research for anxiety disorders in youth.
AB  - This article identifies and addresses three methodological domains relevant to
      the treatment of anxiety disorders in youth: (a) procedural matters, (b) the
      assessment of anxious distress, and (c) the analysis of treatment-produced
      change. Procedural topics include the need to manualize treatment, have diversity
      among participants and comparability of the duration of treatment and control
      conditions, and control for medication status. Multiple-method measurement issues
      include child and parent reports, observations, and structured interviewing. Our
      examination of change issues considers comorbidity, analyzing the intent-to-treat
      sample, treatment "spillover," and clinical as well as statistical significance.
      Problems are identified and potential ameliorative strategies are offered.

PMID- 9566543
TI  - Psychotherapy: definitions, mechanisms of action, and relationship to etiological
      models.
AB  - In this paper, we define psychotherapy as a modality of treatment in which the
      therapist and patient(s) work together to ameliorate psychopathologic conditions
      and functional impairment through focus on the therapeutic relationship; the
      patient's attitudes, thoughts, affect, and behavior; and social context and
      development. The possible mechanisms of action and active ingredients of
      psychotherapy in children and adolescents are discussed, with an emphasis on the
      above-noted domains. The adult psychotherapy literature strongly supports the
      central roles of the therapeutic relationship and therapeutic empathy; this has
      been much less intensively explored in the child and adolescent psychotherapy
      literature. Similarly, there have been few studies examining the mediation of
      treatment effects by impact on specific domains. Ideally, treatment studies
      should gather data that can be informative about the impact of putative mediating
      and moderating psychosocial and biological variables on outcome and course. The
      results of such studies can aid further refinements in both theories of etiology
      and improvement in treatments for children and adolescents.

PMID- 9566545
TI  - Predicting the outcome of treatment.
AB  - The clinical question--"Which treatment(s) for which patients with what set of
      subgrouping characteristics working by what mechanism(s)?"--rests at the heart of
      differential therapeutics. Experimentally, this question reduces to a test of how
      well we can predict the outcome of treatment using the treatment conditions plus
      other moderating and mediating variables. Reflecting the discussions held at a
      recent National Institute of Mental Health (NIMH) conference on psychosocial
      treatments, and using pediatric anxiety disorders as a case in point, we discuss
      the problem of prediction in treatment outcome studies from the standpoint of
      definition of terms, using the general linear model of prediction. We also
      outline types of studies that may be useful in testing potential predictors, and
      put forward a possible matrix of predictor variables as currently implemented in
      an NIMH-funded treatment outcome study of pediatric obsessive-compulsive disorder
      (OCD). We conclude by making specific suggestions for implementing a broader
      approach to the study of predictors.

PMID- 9566546
TI  - The analysis of intervention change in children and families: methodological and
      conceptual issues embedded in intervention studies.
AB  - This article provides an overview of methodological and conceptual issues
      underlying the assessment of change during psychotherapy with children and
      families. Three central considerations are discussed: (1) What changes do we
      measure? (2) When do we measure change? (3) How do we measure change? The
      difficulties with the traditional methods of assessing change are highlighted,
      and suggestions for a new paradigm that calls for expansion of the nomological
      network relevant to the analysis of change, as well as the inclusion of more
      assessment points and more reliable and valid measures of the change process, are
      presented. Illustrations of key points are provided from the Adolescent
      Transitions Program, a theoretically based intervention program targeting high
      risk youth.

PMID- 9566548
TI  - Phylogenetic analysis of HIV type 2 strains from Portugal.

PMID- 9566547
TI  - Child and adolescent psychotherapy research: developmental issues.
AB  - Describes developmental issues that pose current challenges to the design of
      treatment outcome investigation with children and adolescents. Normal childhood
      development and the development of childhood disorders are discussed using the
      transactional model of development. Challenges in diagnostic decision making, the
      selection of the most appropriate treatment regimen, and the measurement methods
      are highlighted. Recognition of the need to study child treatments through long
      term follow-up periods underscores the need for resolution of these developmental
      issues.

PMID- 9566549
TI  - Neutralizing antibody and perinatal transmission of human immunodeficiency virus
      type 1. New York City Perinatal HIV Transmission Collaborative Study Group.
AB  - The major immunologic determinants for perinatal transmission of human
      immunodeficiency virus type 1 (HIV-1) remain largely unknown. The presence of
      maternal neutralizing antibodies has been proposed as an explanation for why the
      majority of infants born to untreated HIV-1-infected women do not become
      infected. Using maternal and infant specimens collected as part of a longitudinal
      cohort study of perinatal transmission in New York City between 1991 and 1995, we
      successfully obtained primary viral isolates from 10 of 20 perinatally
      nontransmitting (NTR) women, 14 of 20 perinatally transmitting (TR) women, and 13
      of 13 of their HIV-1-infected infants. Neutralizing antibody titers were then
      determined using a titer reduction assay. TR and NTR women did not differ in
      their ability to neutralize autologous virus or laboratory strains LAI and MN.
      Infant viruses were not less sensitive to neutralization by maternal sera than
      autologous viruses. Similarly, TR and NTR isolates were neutralized equally well
      using a reference serum with broad neutralizing ability. Finally, a heteroduplex
      tracking assay (HTA) was used to analyze the degree of viral homology within 13
      TR maternal-infant pairs. In eight pairs, maternal and infant isolates were
      highly homologous. In five pairs, lesser degrees of homology were observed,
      consistent with perinatal transmission of a minor species. However, these
      isolates were no more or less resistant to maternal sera than were homologous
      isolates. Thus we found no association between the presence of neutralizing
      antibody in maternal sera as measured by a titer reduction neutralization
      (inactivation) assay and perinatal transmission of HIV-1.

PMID- 9566550
TI  - Active immunization of patients with HIV infection: a study of the effect of
      VaxSyn, a recombinant HIV envelope subunit vaccine, on progression of
      immunodeficiency.
AB  - Infection with the human immunodeficiency virus (HIV) leads to a progressive
      immunodeficiency characterized by decreasing levels of CD4+ T lymphocytes.
      VaxSyn, a vaccine based on the recombinant envelope glycoprotein subunit (rgp160)
      of HIV-1IIIB, was used to immunize HIV-infected patients to determine whether its
      administration was beneficial with respect to slowing disease progression. A 3
      year multicenter, randomized, placebo-controlled, double-blinded, efficacy and
      safety trial of repeated immunization with VaxSyn was used to evaluate the long
      term impact on the progression of immunodeficiency. VaxSyn in alum, or alum
      alone, was given to 278 HIV-infected asymptomatic individuals with initial CD4
      counts of > or =500 cells/mm3. Clinical findings, the CD4 count, and both
      virological and immunological parameters were followed. No significant
      differences were observed between the treatment and placebo control groups in
      rate of CD4 T cell decline, time to initiation of antiretroviral therapy,
      incidence of opportunistic infections, HIV RNA plasma viremia, HIV viral
      infectivity as measured by quantitative HIV coculture assay, and death. This
      study revealed no effect on either clinical or laboratory virological parameters
      from the administration of VaxSyn.

PMID- 9566551
TI  - Anti-F(ab')2 antibody in HIV type 1 infection: relationship to
      hypergammaglobulinemia and to antibody specific to the V3 loop region of
      glycoprotein 120.
AB  - As HIV infection and autoimmune disease share certain similarities, it has been
      suggested that HIV may disrupt control of humoral immunity by the antiidiotype
      network, and that this may be evident as increased IgG antibody to F(ab')2. When
      anti-F(ab')2 was quantified by ELISA in sera of randomly chosen HIV-infected
      versus uninfected donors, some HIV-infected sera did contain increased anti
      F(ab')2, resulting in a median amount twofold higher than in uninfected sera.
      Moreover, when data were grouped by blood CD4 lymphocyte count, anti-F(ab')2 in
      HIV+ groups appeared to rise as CD4 lymphocytes declined. However, increased anti
      F(ab')2 mirrored the elevation in serum IgG closely, and normalization of anti
      F(ab')2 to serum IgG concentration equalized the groups so that no relationship
      to CD4 lymphocytes remained. Hypergammaglobulinemia is therefore strongly
      implicated as a cause of variation in anti-F(ab')2. After dissociation of immune
      complexes, anti-F(ab')2 activity per microgram of monomeric IgG was slightly
      increased over normal only in the HIV-infected group with fewest CD4 lymphocytes,
      without statistical significance. In contrast, the proportion of IgG antibody to
      the V3-neutralizing determinant in HIV-1 decreased significantly as disease
      advanced. The same was true for 12 HIV+ individuals studied longitudinally for
      500-1300 days. The data suggest that measuring serum anti-F(ab')2 is misleading
      when immune complexes are present: apparent increases as disease progresses are
      due to increased IgG and, possibly, to related technical artifacts. During HIV
      infection, the proportion of antiidiotypic IgG in fact remains unaltered or
      falls, making this an unlikely cause of suppressed humoral immunity to HIV-1.

PMID- 9566552
TI  - Ciprofloxacin inhibits activation of latent human immunodeficiency virus type 1
      in chronically infected promonocytic U1 cells.
AB  - The effect of ciprofloxacin, a quinolone antibiotic widely used to treat
      opportunistic bacterial infections in AIDS patients, was examined in the context
      of reactivation of latent HIV-1 in chronically infected promonocytic U1 cells.
      Ciprofloxacin inhibited, in a dose-dependent manner, HIV-1 expression in U1 cells
      activated with phorbol 12-myristate 13-acetate (PMA). The inhibitory effect of
      ciprofloxacin was associated with a reduction in the production of tumor necrosis
      factor alpha, inhibition of activation of transcriptional factor NF-kappaB, and
      HIV LTR-driven gene expression. Furthermore, ciprofloxacin inhibited TNF-alpha
      induced HIV expression in U1 cells. The concentrations of ciprofloxacin that
      inhibited HIV production are readily achievable in vivo.

PMID- 9566553
TI  - Low CD83, but normal MHC class II and costimulatory molecule expression, on
      spleen dendritic cells from HIV+ patients.
AB  - Dendritic cells (DCs), which are the most potent antigen-presenting cells for T
      lymphocytes, are targets for HIV in vitro and in vivo. Antigen presentation by
      DCs has been suggested to be impaired during HIV infection; however, the extent
      to which DCs from HIV+ individuals are altered, particularly in lymphoid organs
      where T cell stimulation takes place, is not clear. To address this question, the
      levels of expression of functionally important molecules by spleen DCs from HIV+
      patients (n = 6), and HIV- organ donors (n = 5) were compared. By rare event
      analysis of flow cytometry data, spleen DCs from HIV+ patients were not depleted,
      representing 0.6 +/- 0.4% of spleen mononuclear cells compared with 0.8 +/- 0.5%
      in HIV- spleens. Fresh HIV+ spleen DCs were MHC II+ and weakly CD86+CD40+, but
      negative for CD83 and CD80, and hence had a normal phenotype, showing no signs of
      in vivo activation. After 24 hr of culture, they upregulated the expression of
      MHC II, CD40, CD80, and CD86 to levels just as high as those on DCs from organ
      transplant donors. However, cultured DCs from HIV+ spleens showed lower
      expression of CD83, compared with DCs from HIV- spleens. The biological
      significance of this observation will be appreciated further when the function of
      this molecule is better known. These results suggest that putative defects in
      antigen presentation by DCs from HIV+ patients are not related to the surface
      expression of MHC II, CD40, CD80, or CD86.

PMID- 9566554
TI  - Multiply spliced env and nef transcripts of simian immunodeficiency virus from
      West African green monkey (SIVagm-sab).
AB  - We have characterized the spliced transcripts of nef and envelope genes of SIVagm
      from African green monkey of the sabaeus subspecies. Most of the transcripts we
      have studied, representing the most abundant mRNA species in our assay, have
      undergone a specific splicing event that removes a part of the trans-activation
      response (TAR) element. This region is predicted to form a stable secondary
      structure (four stem-loop elements in SIVagm-sab) that affects the trans
      activation of viral gene expression by Tat and the translation of the viral
      transcripts. Contrary to what is observed in other viruses, in which this R
      region splicing has also been described (e.g., HIV-2), the LTR splicing in SIVagm
      sab removes part of the first stem-loop and the following ones, nearly completely
      disrupting the TAR element secondary structure. Because LTR splicing seems to be
      a conserved feature among the strains we have characterized, these results
      suggest that this phenomenon could have important consequences for virus
      replication, pathogenicity, and latency.

PMID- 9566555
TI  - Herpesvirus saimiri transformation of HIV type 1 suppressive CD8+ lymphocytes
      from an HIV type 1-infected asymptomatic individual.
AB  - CD8+ T lymphocytes from HIV+ individuals can potently suppress HIV-1 replication
      in a noncytolytic manner. This suppression appears to be multifactorial and the
      molecules contributing have not been fully elucidated. As an approach to this
      question we used herpesvirus saimiri (HVS) to transform CD8+ T lymphocytes from
      an HIV+ asymptomatic donor to a continuously growing, activation-independent, IL
      2-dependent phenotype. The transformed cell population, termed CD8(HVS), had an
      activated phenotype, contained HVS sequences, did not shed infectious HVS virus,
      and was polyclonal. The CD8(HVS) cells, despite the absence of detectable CTL
      activity, potently suppressed HIV-1 production by both autologous and
      heterologous CD4+ cells from infected donors. The CD8(HVS) cells in coculture
      also suppressed virus production from PBMCs acutely infected with syncytium
      inducing (SI) strains or NSI primary isolates of HIV-1. The supernatants from the
      CD8(HVS) cells and their concentrates derived from these supernatants were
      suppressive to NSI primary isolates of HIV-1 but not to SI strains. Fractionation
      of these concentrates showed that the suppressive activity was associated with
      low molecular mass (6500- to 19,300-Da) protein species. Western blotting and
      ELISA indicated that the CC chemokines MIP-1alpha, MIP-1beta, and RANTES were
      present in these fractions. Antibody-blocking studies with antibodies to the CC
      chemokines indicated that a significant portion of the soluble HIV-suppressive
      activity was due to these molecules. However, these experiments also suggested
      the inhibitory activity of the CD8(HVS) cells in coculture is not due exclusively
      to the CC chemokines. The HVS-transformed cells provide a useful tool for the
      study of noncytolytic CD8+ T lymphocyte-mediated suppression of HIV-1.

PMID- 9566556
TI  - Geographic and demographic differences in the frequency of human cytomegalovirus
      gB genotypes 1-4 in immunocompromised patients.
AB  - To test the hypothesis that human cytomegalovirus (CMV) gB genotype may differ
      with geographic origin or patient demographics, CMV DNA was amplified for gB
      typing from immunocompromised patients in Italy and Africa and compared with
      previously reported frequencies in California. Increased gB2 frequency occurred
      in Italian homosexual AIDS patients, as compared with both Italian heterosexual
      injection drug users with AIDS and heterosexual Zimbabwe AIDS patients.
      Occurrence of gB3 in Italy was higher in injection drug users than in homosexual
      AIDS patients. The incidence of gB4 was higher overall in the Italian as compared
      with the California patients. Therefore geographic and demographic differences in
      patients affect gB distribution and should be considered before associations of
      gB genotypes and virulence are made.

PMID- 9566557
TI  - Identification and molecular characterization of human T lymphotropic virus type
      II infections in intravenous drug abusers in the former South Vietnam.
AB  - Previous serological studies have demonstrated that some 60% of intravenous drug
      abusers (IVDAs) in urban areas of the former South Vietnam are infected with HTLV
      II. In the present report we have attempted to characterize the viruses using
      restriction fragment length polymorphism (RFLP) and nucleotide sequence analysis
      of the provirus long terminal repeat (LTR) region. RFLP analysis of nine samples
      demonstrated that all were infected with the HTLV-IIb subtype. The HTLV-IIa
      subtype was not detected. Phylogenetic analysis of the nucleotide sequences
      demonstrated that the viruses clustered closely with HTLV-IIb isolates present in
      IVDAs from the New York City area. The present molecular analysis together with
      the previously reported absence of HTLV-II infection in North Vietnam supports
      the view that HTLV-II may have been introduced from the United States to this
      part of Asia by military personnel during the Vietnam conflict.

PMID- 9566558
TI  - Evaluation of the biliary tree during laparoscopic cholecystectomy: laparoscopic
      ultrasound versus intraoperative cholangiography: a prospective study of 150
      cases.
AB  - From November 1994 to March 1996, 150 patients treated by laparoscopic
      cholecystectomy were included in a prospective study, to compare intraoperative
      cholangiography (IOC) and laparoscopic ultrasonography (LU). The biliary tree was
      successively explored by these two methods in the routine detection of common
      bile duct stones. The feasibility of LU was 100%. Cholangiography was performed
      only in 125 cases (83%). The time taken for LU was significantly shorter (11.6
      vs. 17.6 minutes, p = 0.0001). In this study, common bile duct stones were found
      in 14 cases (9%). For their detection, results were comparable to LU and IOC. For
      LU, sensitivity was 80% and specificity 99%; and for IOC, 78 and 97%,
      respectively. Both examinations combined had a 100% sensitivity and specificity.
      Laparoscopic ultrasonography failed to recognize the intrapancreatic part of the
      common bile duct in 25 cases (17%) and did not show anatomic abnormalities
      detected by IOC. It did, however, detect other unsuspected intraabdominal
      abnormalities. Although LU is safe, repeatable, and noninvasive, a considerable
      learning curve is necessary to optimize its efficacy. Comparison of relative cost
      must be undertaken.

PMID- 9566559
TI  - Open versus laparoscopic gastrojejunostomy for palliation in advanced pancreatic
      cancer.
AB  - To assess short-term outcome of open (OGJ) versus laparoscopic (LGJ)
      gastrojejunostomy in palliation of gastric outlet obstruction (GOO) caused by
      advanced pancreatic cancer, 22 OGJ patients were compared with 9 diagnosis
      matched LGJ controls operated on at the same hospital between 1991 and 1996.
      Patients undergoing OGJ and LGJ were comparable for age, gender, weight, American
      Society of Anesthesiologists grading, and previous extensive abdominal surgery,
      but not for gastroenterostomy performed as a prophylactic procedure (9 vs. 0,
      respectively). Mortality (5 vs. 1, p = 1.5), overall morbidity (9 vs. 3, p =
      0.42), operating time (113.6 +/- 24.5 minutes vs. 125 +/- 15.2 minutes, p < 0.5),
      time to oral solid food intake (7.2 +/- 0.9 days vs. 5.3 +/- 1.3 days, p < 0.5),
      nonsteroidal anti-inflammatory drug consumption (7,563.6 +/- 3,381.3 mg vs. 2,044
      +/- 673 mg, p < 0.5), opioid consumption (688.5 +/- 258.6 mg vs. 2,910.5 +/-
      2,659.9 mg, p < 0.5), delayed-return gastric emptying (5 vs. 1, p = 0.12),
      postoperative hospital stay (14.6 +/- 1.9 days vs. 10.1 +/- 1.8 days, p < 0.5),
      survival (5.7 +/- 0.8 months vs. 4.6 +/- 0.6 months, p < 0.5), and further
      hospital stay before death (9.8 +/- 3.3 days vs. 11.6 +/- 3.4 days, p > 0.5) were
      not significantly different in 22 OGJ and 9 LGJ patients, respectively. Estimated
      blood loss was significantly lower in LGJ patients (270.2 +/- 45.8 ml vs. 66 +/-
      15.7 ml, p < 0.01). When 13 of 22 patients undergoing OGJ for treatment were
      compared with 9 LGJ patients, only estimated blood loss (p < 0.01) and hospital
      stay (p < 0.05) were significantly reduced in LGJ patients. Recurrent GOO before
      death occurred in one patient (1 of 22, 4.5%) 9 months after OGJ. LGJ for
      palliative treatment of GOO in advanced pancreatic cancer offered (in spite of
      the learning curve) reduced estimated blood loss and hospital stay when compared
      with OGJ.

PMID- 9566560
TI  - Microcirculation in lower limbs during laparoscopic cholecystectomy.
AB  - To study the influence of venous hypertension, which develops in lower limbs
      under pneumoperitoneal pressure, on microcirculation, plethysmographic
      measurements were performed in patients before and during laparoscopic and
      traditional (open) cholecystectomy. During laparoscopy, isovolumetric venous
      pressure (estimate of capillary pressure), and filtration coefficient (estimate
      of patent capillary surface) decreased, which was not the case during open
      surgery. These results indicates that venous hypertension during laparoscopic
      surgery does not extend to the microcirculation; vasoconstriction is a result of
      protective mechanisms, which disable excessive fluid filtration in
      microcirculation. Parameters of macrocirculation (ambient venous pressure,
      compliance of calf tissue) changed intraoperatively in both groups similarly,
      irrespectively of the surgical technique.

PMID- 9566561
TI  - Resistance to venous outflow during laparoscopic cholecystectomy and laparoscopic
      herniorrhaphy.
AB  - The effects of pneumoperitoneum on peak venous flow velocity in the common
      femoral vein and the vena cava have already been studied. The results suggested
      that venous stasis occurs during surgical pneumoperitoneum. This study determines
      the effects of pneumoperitoneum on the overall venous outflow resistance of the
      lower limbs. Venous outflow resistance was measured during surgical procedures by
      impedance plethysmography in 12 patients undergoing laparoscopic cholecystectomy,
      4 patients undergoing laparoscopic herniorrhaphy, 4 patients undergoing
      conventional cholecystectomy, and 2 patients undergoing conventional
      herniorrhaphy. Venous outflow resistance did not change significantly during
      laparoscopic cholecystectomy or herniorrhaphy. No difference in venous outflow
      resistance between laparoscopic cholecystectomy and herniorrhaphy was found.
      During pneumoperitoneum, no obstruction to total lower limb venous outflow could
      be demonstrated, indicating that venous stasis in the limbs did not occur, and
      consequently, flow in the iliac and inferior caval veins was not compromised.
      Hypothetically, active vasodilatation resulting from mild compression may explain
      this. In our view, no special measures to prevent deep venous thrombosis have to
      be taken during laparoscopic procedures.

PMID- 9566562
TI  - Treatment of primary and secondary spontaneous pneumothorax using
      videothoracoscopy.
AB  - Our aim is to assess the results of surgical treatment for spontaneous
      pneumothorax (SP) using video-assisted thoracoscopic surgery (VATS) and to
      determine whether this technique is equally effective for primary SP (PSP) and
      secondary SP (SSP). A prospective study was performed on 54 patients with
      persistent and recurrent SP (42 PSPs and 12 SSPs). Mean operating time, time
      before drainage removal, and hospital stay were significantly longer with SSP
      (67.1 vs. 48.1 minutes; 5.4 vs. 3.6 days; and 7.7 vs. 5.3 days; p < 0.01,
      respectively). There was one conversion due to bleeding (PSP). Postoperative
      complications were greater with SSP (33% vs. 12%; p = 0.09). Although these were
      mild in all cases, the most common was air leak (25 vs. 5%; p = 0.06). The SP
      persisted in three cases [2 (5%) with PSP, and 1 (8%) with SSP] and recurred in 2
      (1 in each group; 2% and 8%, respectively). Follow-up averaged 24 months. VATS is
      effective in the surgical treatment of PSP and SSP, although the technical
      difficulty, morbidity rate, hospital stay, and incidence of persistences and
      recurrences are greater in the latter than in the former.

PMID- 9566563
TI  - Does chemical composition have an influence on the fate of intraperitoneal
      gallstone in rat?
AB  - Perforation and spillage of gallstones is a common occurrence in laparoscopic
      cholecystectomies. The long-term complications of these stones remains
      controversial. Experimental studies have been carried out to elucidate the
      outcome of intraperitoneal gallstones, but the chemical composition of these
      stones has not been considered in previous studies. In this study, we
      investigated the local effects of intraperitoneal gallstones in rats with respect
      to their chemical composition. Bile and gallstones were taken from human
      cholecystectomy specimens, and sent for bacteriologic and chemical analysis.
      Twenty cholesterol and 10 pigment stones were placed in the abdominal cavity of
      rats. Long-term local effects of gallstones were determined at the end of 3
      months with macroscopic and microscopic examination. The fragments of two pigment
      stones were infected by Staphylococcus aureus. Five (17%) cholesterol stones were
      found free in the abdominal cavity, and 25 stones (83%) were wrapped with
      adjacent structures. Granuloma formation was found around 4 pigment stones (13%
      of all stones, 40% of pigment stones; p = 0.0077). We observed large granulomas
      and cutaneous fistula formation in two rats with infected pigment stones placed
      in the abdominal cavity. Histhopathologic examination also showed significantly
      severe inflammatory reactions secondary to pigment stones (p<0.001). In
      conclusion our findings revealed that chemical composition has a significant
      influence on the fate of intraabdominal gallstones, and infection may aggravate
      local reactions and complications. Based on our findings, laparoscopic retrieval
      of spilled stones whenever possible seems to be useful to prevent subsequent
      infectious complications and inflammatory reactions. Patients with retained
      intraperitoneal pigment stones after laparoscopic cholecystectomy must be
      followed up closely.

PMID- 9566564
TI  - Rectal expander-assisted transanal endoscopic microsurgery in rectal tumors.
AB  - Rectal expander-assisted transanal endoscopic microsurgery (RE-TEM) was performed
      for two cases of early rectal cancer and a case of villous tumor under saddle
      block anesthesia. RE-TEM is the new technique for local excision of rectal tumors
      with a rectal expander that we developed. The rectal expander expands the rectum
      after insertion through the anus and provides adequate vision for microsurgery
      with standard video monitors. Tumors were located 8, 8, and 5 cm from the anal
      verge, and all of them were excised completely with no difficulty. Minor bleeding
      was noted in all cases and was controlled by electric coagulation and/or sutures.
      Average operative time for the three cases was 105 min. We conclude that RE-TEM
      is useful for rectal tumors and/or early rectal cancer that cannot be removed by
      endoscopy.

PMID- 9566565
TI  - A prospective review of laparoscopic cholecystectomy in Brunei.
AB  - Brunei has a small population and a unique medical setup: The number of
      laparoscopic cholecystectomies (LCs) performed in our institution represents the
      total number of cases performed in this country. A prospective analysis of all
      the LCs performed in Brunei is presented. All 220 LCs performed between February
      1, 1992, and November 30, 1996, were prospectively recorded on a detailed
      protocol. Analyses were made with respect to preoperative patient demography,
      intraoperative complications, and postoperative morbidity and mortality.
      Symptomatic gallstone disease was found to be common among the ethnic Nepalese
      population. In this series, nine patients required conversion to open surgery
      (4%). Acute cholecystitis comprised 21% of cases, and the mean operating time was
      longer in these cases (144.1 min) than in elective cases (101.2 min; P = 0.002).
      The overall morbidity was 5% with one ductal injury (0.5%). The mortality rate in
      this series was 0.5%. Our results of LC are favorable and comparable with those
      of published series. We conclude that LC has been successfully introduced into
      our institution. This study also represents an unofficial audit of the state of
      development of LC in Brunei.

PMID- 9566566
TI  - Intraoperative endoscopy during colorectal surgery.
AB  - In cases where preoperative studies may have been inadequate or could not be
      performed, intraoperative endoscopy (IOE) becomes an essential investigative tool
      for identification of synchronous lesions, of nonpalpable lesions, of sources of
      bleeding, and localization of lesions during laparoscopic colonic surgery. We
      report our experience with IOE, and describe our techniques of transabdominal
      colonoscopy. A review of the IOE performed in hospitals affiliated with the
      University of Miami was done. Fifty-eight patients received IOE from July 1994 to
      August 1996. There were 47 colonoscopies (38 transanal and 9 transabdominal), and
      11 flexible sigmoidoscopies. Colorectal cancer, diverticulitis, inflammatory
      bowel disease, and lower gastrointestinal bleeding represented 83% of cases. In
      10% of cases IOE changed the extent of the surgical procedure. There were no
      complications related to IOE. We conclude that in selected patients undergoing
      colorectal procedures, IOE is an essential tool. It can be performed safely,
      effectively, and rapidly.

PMID- 9566567
TI  - Laparoscopic vagotomy and open pyloroplasty for bleeding duodenal ulcer not
      controlled endoscopically.
AB  - The majority of our patients with bleeding duodenal ulcer responded to endoscopic
      injection treatment. However, in six patients admitted during a 2 1/2-year
      period, we were forced to do emergency surgery to control the hemorrhage (three
      with failed injection and persisting exsanguination from a brisk bleeder and
      three rebled soon after apparent initial hemostasis). We performed an innovative
      procedure: pyloroplasty was done after oversewing the arterial bleeder in the
      duodenum through a small transverse wound in the right upper quadrant. The wound
      was then closed around a 10-mm trocar sheath. With the addition of three more
      ports, a truncal vagotomy was completed laparoscopically. Recovery was rapid and
      uneventful in all six cases; postoperative pain was minimal. The mean operative
      time was 85 minutes. We believe that, in a selected group of patients,
      laparoscopic vagotomy and open pyloroplasty through an essentially extended port
      wound (as described in detail) is an expedient and effective procedure in the
      emergency setting.

PMID- 9566568
TI  - Value of peritoneal lavage cytology during laparoscopic staging of patients with
      gastric carcinoma.
AB  - Forty-nine consecutive patients with advanced gastric carcinoma underwent
      preoperative staging by laparoscopy between June 1991 and June 1992. Peritoneal
      lavage with cytologic examination was performed when ascites was not present. In
      eight cases (16.3%), laparoscopy revealed carcinomatosis and/or multiple hepatic
      metastases, so laparotomy was not performed. Intraperitoneal free cancer cells
      (IFCCs) were detected in 41% of patients (65% in patients with ascites and 28% by
      peritoneal lavage). In the absence of macroscopic peritoneal dissemination, IFCCs
      were encountered in 29% of patients. IFCCs were present only when invasion of the
      gastric serosa was >3 cm2 or when adjacent organs and structures were already
      invaded. Mucinous adenocarcinoma, Borrmann class IV tumors, and Stage IV patients
      had higher incidence of IFCCs. Cytologic results were similar at laparoscopy and
      laparotomy (p > 0.05). Therefore, cytologic evaluation of peritoneal lavage added
      sensitivity to laparoscopy in assessing patients with advanced gastric carcinoma
      and may alter their therapeutic approach.

PMID- 9566569
TI  - Videolaparoscopic treatment of Spigelian hernias.
AB  - Because treatment for Spigelian hernia is rarely discussed in the literature,
      this report presents two cases observed in a recent 6-month period by the U.O.A.
      Independent General Surgery Department, Hospital of Este. Both patients had
      laparoscopic treatment using a polypropylene prosthesis, which confirms the
      technological validity of the surgical method. The described cases are
      emblematic, because the intervention permitted a resolution of associated
      pathologies (gallbladder gallstones and umbilical hernia), which confirms both
      the efficacy of the surgical technique and of the high diagnostic precision of
      laparoscopy, as it is described by several sources. The validity of the technique
      is also confirmed by the quick recovery of patients and by the reduced
      hospitalization time, especially in elderly patients and in precarious general
      conditions.

PMID- 9566571
TI  - Video-assisted thoracoscopic resection of an epiphrenic diverticulum with
      esophagomyotomy and partial fundoplication.
AB  - Videothoracoscopic stapled diverticulectomy with distal esophageal myotomy and
      partial fundoplasty was successfully done for a 65-year-old woman who had a
      large, symptomatic epiphrenic diverticulum associated with achalasia. This
      minimally invasive approach resulted in good symptomatic relief of dysphagia,
      minimal postoperative pain, a 1-day hospital stay, and early return to normal
      activity.

PMID- 9566570
TI  - Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectomy
      with special reference to postoperative pain.
AB  - To study the possible benefits of N2O pneumoperitoneum, 40 patients scheduled for
      laparoscopic cholecystectomy for symptomatic cholelithiasis were randomized into
      either CO2-induced (n = 20) or N2O-induced (n = 20) pneumoperitoneum groups. The
      intensity of postoperative pain was assessed by the patients themselves using an
      visual analogue pain score scale. CO2 insufflation caused respiratory acidosis.
      The total amount of anesthetic enflurane needed was lower in the N2O than in the
      CO2 group (p < 0.041). The N2O group experienced less pain 1 hour (p < 0.040) and
      6 hours (p < 0.017) postoperatively and the next morning. Serum cortisol and
      plasma adrenaline concentrations in the N2O group did not differ from those in
      the CO2 group. Patients with N2O pneumoperitoneum seem to have less pain without
      the side effects caused by CO2. The N2O pneumoperitoneum is a good alternative to
      the CO2 pneumoperitoneum, especially for prolonged laparoscopic operations in
      patients with chronic cardiopulmonary diseases.

PMID- 9566572
TI  - A minimally invasive technique of appendectomy using a minimal skin incision and
      laparoscopic instruments.
AB  - To take advantage of the laparoscopic procedure, a new minimally invasive
      technique of appendectomy for nonobese and uncomplicated appendicitis is
      presented. Initially, diagnostic laparoscopy is performed through a minimal skin
      incision (microceliotomy) 1.5-2.0 cm in length in the right lower abdomen to rule
      out other disease. Then an appendectomy is performed using conventional surgical
      instruments under direct vision through the previous skin incision. There were 18
      women and 12 men in this series. The mean age was 22.6 years. Pathologic findings
      of the appendix were: 2 normal, 13 catarrhal, 10 suppurative, and 5 gangrenous
      type. The mean operation time was 30.7 min. The mean frequency of postoperative
      analgesic requirement (nalbuphine 0.2 mg/kg) was 0.9 times. The mean hospital
      stay was 4.1 days (range, 2-7 days), and the duration until return to full
      activity was 7.6 days (range, 5-14 days). There was no mortality or morbidity.
      This appendectomy technique is a useful method for minimizing the postoperative
      pain and operative scar, thus allowing the patient an early return to full
      activity.

PMID- 9566573
TI  - Laparoscopic repair for perforation of duodenal ulcer with omental patch: report
      of initial six cases.
AB  - We report our initial experience with perforated duodenal ulcer treated by
      laparoscopic repair with omental patch in six patients, and the results are
      compared with those of other procedures retrospectively. The average operative
      time was 85.0 min, and the estimated blood loss was 13.7 ml. The estimated blood
      loss of laparoscopic repair was significantly less than that of gastrectomy (p <
      0.01). However, although all patients with gastrectomy or open omental patch
      needed administration of analgesia, only half of patients require analgesia in
      laparoscopic repair. No postoperative complication was encountered, and the
      recurrence of ulcer was not recognized in a mean follow-up of 10 months. We
      recognized this procedure to be safe and feasible. Although a larger number of
      patients with longer follow-up is needed, this procedure may become one of the
      treatments for perforated duodenal ulcer.

PMID- 9566574
TI  - Is it necessary to catheterise the bladder before laparoscopy?
AB  - Fifty patients had residual urine measured by catheterisation immediately before
      laparoscopic cholecystectomy. The median amount of urine in the bladder was 100
      ml (range 5-500 ml). This urine volume does not distend the bladder enough to
      risk inadvertant perforation during insertion of a subumbilical port. Urinary
      bladder catheterisation is unnecessary before laparoscopy especially if the
      bladder is impalpable.

PMID- 9566575
TI  - Three-trocar laparoscopic cholecystectomy: a cautionary note.

PMID- 9566576
TI  - Remedying some complications of laparoscopic cholecystectomy.

PMID- 9566577
TI  - Modification of Veress needle insertion.

PMID- 9566578
TI  - Manda, a fermented natural food, suppresses lipid peroxidation in the senescent
      rat brain.
AB  - The level of lipid peroxidation reflects the degree of free radical-induced
      oxidative damage in brain tissue of the elderly. We examined the effects of
      Manda, a product prepared by yeast fermentation of several fruits and black
      sugar, on lipid peroxidation in the senescent rat brain as model of aging.
      Senescent rats were provided with a diet containing 50 g/100 g Manda for 8 days,
      supplemented on day 8 with an intragastric administration of Manda (6.0 g/kg body
      wt.) twice daily. The hydroxyl radical scavenging activity was generated by the
      FeSO4-H2O2 system and analyzed by electron spin resonance spectrometry. Using
      this method, the addition of Manda (2.88 mg/ml) to brain homogenates of adult
      rats (0.06 mg/ml) had an additive inhibitory effect on lipid peroxidation
      compared with control adult rats not treated with Manda. Incubation of brain
      homogenates with Manda for 2 h and 3 h, significantly inhibited the increase in
      lipid peroxides (malondialdehydes and 4-hydroxyalkenals) levels in aged rats due
      to auto-oxidation. In addition, oral administration of Manda significantly
      suppressed the age-related increase in lipid peroxidation in the hippocampus and
      striatum, although such change was not observed in the cerebral cortex. Although
      Manda contains trace level of alpha-tocopherol, the level of alpha-tocopherol in
      Manda did no correlate with its antioxidant effect. Our results suggest that
      Manda protects against age-dependent oxidative neuronal damage caused by
      oxidative stress and that this protective effect may be due, in part, to its
      scavenging activity against free radicals.

PMID- 9566579
TI  - Changes in [3H]forskolin binding to adenylate cyclase and [3H]phorbol dibutyrate
      binding to protein kinase C in pentobarbital tolerant/dependent rats.
AB  - These studies were designed to examine the effect of chronic administration of
      pentobarbital on activity of adenylate cyclase (AC) and protein kinase C (PKC) in
      the rat brain by autoradiography. Recently, it has been suggested that the
      phosphorylation of specific proteins may be involved in the development of
      physical dependence. An experimental model of barbiturate tolerance and
      dependence was developed using i.c.v. infusion of pentobarbital (300 microg/10
      microl/hr for 7 days) by osmotic minipumps and abrupt withdrawal from
      pentobarbital. The levels of [3H]forskolin binding were elevated (28-67%) in
      cortex, thalamus, dentate gyrus, hippocampal CA3 and cerebellum of the
      pentobarbital withdrawal animals, while these changes were not observed in
      tolerant rats. The levels of [3H]phorbol dibutyrate binding were highly elevated
      (38-65%) in the region of cortex, caudate putamen, septum, thalamus, dentate
      gyrus, and cerebellum of rats withdrawal from pentobarbital. These results show
      that the levels of AC and PKC were significantly elevated in pentobarbital
      withdrawal rats, and suggest that the levels of AC and PKC are altered in a
      region-specific manner during pentobarbital withdrawal.

PMID- 9566582
TI  - Developmental regulation of protein phosphatase types 1 and 2A in post-hatch
      chicken brain.
AB  - The activity and subcellular distribution of protein phosphatases 1 and 2A were
      measured in chicken forebrain and cerebellum during post-hatch development. At
      all post-hatch ages, a large proportion of PP1 and PP2A was membrane bound and
      these enzymes were less active than their cytosolic counterparts. The protein
      concentration of PP1 in the membranes increased 40% between 2 and 14 days and a
      further 60% between 14 days and adult, whereas the PP1 enzyme activity in the
      membranes progressively decreased. In contrast to PP1, the protein concentration
      of PP2A remained constant in all fractions during post-hatch development, and the
      enzyme activity of PP2A did not change except for a decrease in the membrane
      bound activity between 2 and 14 days. These results show that the subcellular
      distribution and activity of PP1 is selectively regulated during post-hatch
      development and that membrane association and inactivation of PP1 are independent
      events.

PMID- 9566580
TI  - Potassium-stimulated taurine release and nitric oxide synthase activity during
      quinolinic acid lesion of the rat striatum.
AB  - The microdialysis technique was used to study the effect of nitric oxide synthase
      (NOS) activity on taurine release. Taurine release was characterized in rat
      striatum that was excitotoxically lesioned compared to normal conditions. The
      basal taurine level of the dialysate decreased during quinolinate (QUIN) lesion
      in parallel to the cell degeneration process. The K+-stimulated taurine
      concentration also decreased during QUIN-lesion, but to an extent that was
      different from that of basal values. K+-stimulated taurine levels were further
      markedly lowered by coapplication of the NOS inhibitor L-NAME in control and in
      lesioned animals up to 30 days after QUIN-injection. Postdegenerative tissue did
      not show any NOS-dependency in K+-induced taurine release. We conclude that a
      substantial part of K+-induced taurine release depends on NOS-activity both in
      normal brain tissue and in excitotoxically induced neurodegeneration. The main
      source of K+-induced taurine release in control rats are neurons but in lesioned
      animals are activated astroglial cells.

PMID- 9566581
TI  - Effects of external pH variations on brain presynaptic sodium and calcium
      channels; repercussion on the evoked release of amino acid neurotransmitters.
AB  - The effects of external pH (pHout) variations on the Na+ and on the Ca2+
      dependent fractions of the evoked amino acid neurotransmitter release were
      separately investigated, using GABA as a model transmitter. In [3H]GABA loaded
      mouse brain synaptosomes, the external acidification (pHout 6.0) markedly
      decreased the Na+ dependent fraction of [3H]GABA release evoked by veratridine
      (10 microM) in the absence of external Ca2+, as well as the Ca2+ dependent
      fraction of [3H]GABA release evoked by high (20 mM) K+ in the absence of external
      Na+. The depolarization-induced elevation of [Na(i)] (monitored in synaptosomes
      loaded with the Na+ indicator dye, SBFI) and the depolarization-induced elevation
      of [Ca(i)] (monitored in synaptosomes loaded with the Ca2+ indicator dye fura-2)
      were also markedly decreased at pHout 6. On the contrary, the external
      alkalinization (pHout 8) facilitated all the above responses. A slight increase
      of the baseline release of the [3H]GABA was observed when pHout was changed from
      7.4 to 8. This effect was only observed in the presence of Ca2+. pHout changes
      from 7.4 to 6 or to 7 did not modify the baseline release of the transmitter. All
      the effects of pHout variations on [3H]GABA release were independent on the
      presence of HCO3-. It is concluded that external H+ regulate amino acid
      neurotransmitter release by their actions on presynaptic Na+ channels, as well as
      on presynaptic Ca2+ channels.

PMID- 9566583
TI  - Intrinsic innervation of a reptilian esophagus (Podarcis hispanica).
AB  - We study the esophagus of Podarcis hispanica through different methods to clarify
      the structure and affinities of its wall innervation. The acetylcholinesterase
      method reveals cholinesterase activity in two submucosal nervous plexuses, with
      an increasing degree of structural complexity in the reptilian esophagus,
      compared with amphibians. Noradrenergic innervation, detected through
      fluorescence induced by formol, widely spreads its network in both the myenteric
      and submucosal plexuses (around the blood vessels in the external submucosal
      plexus, and to the glandular lamina propria in the inner submucosal plexus).
      Immunohistochemistry for vasoactive intestinal peptide shows a widespread
      innervation, with neurons clustered in ganglia and also scattered through the
      VIPergic network, only at the myenteric plexus. Immunohistochemistry for
      substance P shows a rich innervation along the entire wall of the esophagus, more
      concentrated in its caudal region, around the blood vessels. Electron microscopy
      shows the enteric neuronal ultrastructure and its relationship with the esophagus
      wall.

PMID- 9566584
TI  - Regional quantitation of preprodynorphin mRNA in guinea pig gastrointestinal
      tract.
AB  - The endogenous opioid peptide dynorphin has been shown by immunochemical studies
      to be widely distributed in the gastrointestinal tract. The aim of this study was
      to determine basal levels of preprodynorphin (ppDyn) mRNA in different regions of
      the gastrointestinal tract of the guinea pig. A modified sensitive and specific
      solution hybridization RNase protection assay was used to quantitate ppDyn mRNA,
      with confirmation by gel analysis of the RNase protected hybrids and PCR
      amplified cDNA. This method combines high sensitivity and sufficient throughput
      to analyze large number of samples in a single assay. Low but measurable amounts
      of ppDyn mRNA were detected in fundus, duodenum, jejunum, ileum, cecum, and
      rectum. The rectum contained significantly more ppDyn mRNA than the stomach,
      small bowel, and cecum. The muscularis/myenteric plexus layer of both ileum and
      rectum contained a higher concentration of ppDyn mRNA per microg total RNA
      compared to the mucosa/submucosa/submucosal plexus. However, a greater absolute
      amount of ppDyn mRNA (80-85%) localized to the mucosal layer. The greater
      absolute amount of ppDyn mRNA in the mucosal layer may indicate the presence of
      dynorphin in the endocrine cells of the mucosa.

PMID- 9566585
TI  - An in vivo microdialysis study of striatal 6-[18F]fluoro-L-m-tyrosine metabolism.
AB  - In vivo brain microdialysis was used to monitor 6-[18F]fluoro-L-m-tyrosine (FMT)
      uptake and metabolism in the striatum of conscious freely moving rats for 3 hours
      after FMT injection (25 mg/kg, i.v.). Microdialysate collected 20 to 120 min post
      dose, contained FMT at a concentration (0.2 to 0.3 nM) approximately ten-fold
      below that of its metabolite [18F]fluoro-3-hydroxyphenylacetic acid (FPAC; 3.2 to
      3.3 nM). D-amphetamine (2.5 mg/kg, i.p.) injected 120 min after significantly
      increased microdialysate FPAC (3.27 +/- 0.31 nM to 4.51 +/- 0.45 nM) in control
      but not reserpinized rats. Taken together these data demonstrate FMT is heavily
      metabolized following its entry into the striatum yielding FPAC which appears to
      be stored, at least in part, in reserpine sensitive cytoplasmic vesicles.
      Presynaptic retention of FPAC may contribute to the preferential accumulation of
      FMT positron emission tomography (PET) signaling in dopaminergic brain areas.

PMID- 9566586
TI  - Effects of guanine nucleotides on glutamate-induced chemiluminescence in rat
      hippocampal slices submitted to hypoxia.
AB  - Glutamate significantly increased levels of spontaneous chemiluminescence (CL) in
      rat hippocampal slices incubated under hypoxic conditions. Although it has been
      previously shown that guanine nucleotides (GN) displace glutamate from several of
      its receptors, in our study only GMP, as well as the glutamate antagonist MK-801,
      was able to reverse the increase in CL provoked by glutamate. On the other hand,
      not only GTP or Gpp(NH)p failed to reverse the action of glutamate, but they
      increased CL production like glutamate. This effect of GTP/Gpp(NH)p was also
      reversed by GMP. We concluded that, under neurotoxic conditions, GMP acted as an
      antagonist and GTP or Gpp(NH)p acted as agonists of glutamate. These results
      reinforced the evidence of the existence of extracellular site(s) for GN and
      indicated a possible role for GN in excitotoxicity.

PMID- 9566587
TI  - Modulation of nigrostriatal dopaminergic transmission by antisense
      oligodeoxynucleotide against brain-derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) promotes the differentiation and growth
      of developing dopamine (DA) neurons and supports the survival of mature DA cells
      in culture. However, the neurotrophic role of endogenous BDNF in the adult DA
      system in vivo has not been well established. To investigate the hypothesis that
      blockade of endogenous BDNF expression results in DA dysregulation, we used an 18
      mer antisense oligodeoxynucleotide (ODN) targeted to the first ATG codon of the
      BDNF transcript. The biological activity of the antisense ODN was initially
      tested in vitro. In cultured dopaminergic MES 23.5 cells, antisense BDNF (20
      microM) effectively reduced BDNF protein expression and cell survival.
      Furthermore, in primary embryonic mesencephalic cultures, antisense BDNF reduced
      the number of tyrosine hydroxylase positive neurons and inhibited [3H]DA uptake
      in a time- and dose-dependent manner. The specificity of the antisense molecule
      was confirmed by comparing its effects with those of a control ODN having the
      same base composition but in scrambled sequence. In rats, two days following an
      intranigral or intrastriatal injection of antisense BDNF (0.5 microg), we
      observed a two-fold and five-fold increase in nigral DA levels, respectively, but
      no change in striatal DA content. Seven days after an intrastriatal antisense
      BDNF injection, DA levels were elevated in the striatum apparently due to
      decreased DA turnover. These observations suggest that inhibition of endogenous
      BDNF expression tends to augment rather than inhibit nigrostriatal DA
      transmission. Thus, the biological effects of endogenous BDNF on the
      nigrostriatal DA system in the adult organism merits further investigation.

PMID- 9566588
TI  - Novel protein inhibitor of calmodulin-dependent cyclic nucleotide
      phosphodiesterase from glioblastoma multiforme.
AB  - Previous investigations from our laboratory have demonstrated a significant
      reduction in the catalytic function of the 60 kDa and 63 kDa isozymes of
      calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) when comparing
      human cerebral tissue that was free of tumor and glioblastoma multiforme (GBM)
      and gliosarcoma [Lal S., Raju R. V. S., Macaulay R. B. J., and Sharma R. K.
      (1996) Can. J. Neurol. Sci., 23, 245-250]. The results suggested the possibility
      of an endogenously produced inhibitor of CaMPDE expressed in these tumors.
      Further investigation has initially characterized the presence of a heat-labile,
      protein inhibitor of both the 60 kDa and 63 kDa isozymes of CaMPDE. Sephacryl S
      200 gel filtration column chromatography indicated that the inhibitor has an
      apparent molecular weight of 22 kDa and experimental evidence demonstrates that
      this inhibitor protein may act independently of calmodulin, and is therefore a
      novel CaMPDE inhibitor. Previous work on non-CNS tumors has shown high levels of
      CaMPDE activity and absence of an inhibitor. This suggests that a different
      mechanism may exist for the proliferation of these subsets of tumors.

PMID- 9566589
TI  - Effects of ischemic tolerance on mRNA levels of IP3R1, beta-actin, and neuron
      specific enolase in hippocampal CA1 area of the gerbil brain.
AB  - Global cerebral ischemia induced to Mongolian gerbils by ligation of common
      carotid arteries (CCAs) is known to result in injury to the hippocampal CA1
      region. In this study, we examined whether neuronal injury can be depicted by
      measuring levels of mRNA encoding inositol 1,4,5-trisphosphate receptor type 1
      (IP3R1), neuron specific enolase (NSE) and beta-actin and whether these
      measurements can be use to assess ischemic tolerance. Gerbils were subjected
      either to cerebral ischemia induced by ligation of both CCAs for 5 min, or to an
      ischemic tolerance paradigm in which a 2 min ischemic preconditioning was
      performed 24 hr prior to the 5 min ischemia. At 48 hr after the 5 min ischemic
      insult, significant decreases in mRNA levels for IP3R1 (26%), NSE (38%) and beta
      actin (50%) could be observed in the hippocampal CA1 region. Although levels of
      mRNA in the preconditioning group were decreased as compared to the sham control,
      the levels were significantly higher than those in the ischemic group. These
      results indicate the feasibility of using mRNA measurement as a parameter to
      assess cerebral ischemic damage. In addition, based on the differences in the
      decline in mRNA levels between the ischemia group and the preconditioned ischemia
      group, it can be concluded that this ischemic tolerance paradigm could offer
      partial protection (around 45%) against the injury due to the 5 min cerebral
      ischemic insult.

PMID- 9566590
TI  - Activation of transcription factor AP-1 by extracellular ATP in PC12 cells.
AB  - We have previously shown that extracellular ATP caused cell death in PC12 cells
      through activation of its receptors. Oxidative stress has been implicated as a
      mechanism of cell death caused by extracellular ATP. In the present study we
      examined the possible signal transduction cascades leading to cell death by
      extracellular ATP. We found, using the electrophoretic mobility shift assay, that
      transcription factor AP-1 DNA binding activity was stimulated by extracellular
      ATP. Northern blot analysis showed that mRNA levels of c-fos, c-jun were elevated
      after treatment with ATP. The stimulation was receptor mediated, since it was
      blocked by the ATP receptor antagonist, suramin. The stimulated AP-1 binding was
      also blocked by the antioxidant N-acetyl-L-cysteine, indicating that reactive
      oxygen species generated following ATP stimulation were involved in the induction
      of AP-1 activity. It appears that both translational and posttranslational events
      contributed to the increased AP-1 DNA binding since cyclohexamide (a protein
      synthesis inhibitor), genistein (tyrosine kinase inhibitor) and staurosporine
      (PKC inhibitor) each partially blocked the AP-1 activation. Changes in AP-1 DNA
      binding activity may modulate expression of target genes involved in cell death
      pathways.

PMID- 9566591
TI  - Arecoline stimulation of radiolabeled arachidonate incorporation from plasma into
      brain microvessels of awake rat.
AB  - The cholinergic agonist, arecoline, was used to examine the effects of
      cholinergic stimulation upon incorporation of radiolabeled arachidonic acid from
      blood into cerebral microvessels of awake rats. Animals received a single i.p.
      injection of arecoline (1 mg/kg) followed 3 to 5 minutes later by a 5 minute
      intravenous infusion of [1-14C]arachidonic acid (AA) (170 microCi/kg) via the
      femoral vein. Timed arterial blood samples were collected over 20 minutes
      following the start of infusion, after which the animal was killed, and the brain
      was removed. The incorporation coefficient k* for [1-14C]AA was approximately 2
      fold higher in microvessels isolated from arecoline-injected than from sham
      injected animals. The data demonstrate in an in vivo paradigm, that activation of
      cholinergic pathways within the rat CNS stimulates arachidonic acid turnover in
      cerebral microvessels. This suggests a direct involvement of this fatty acid in
      second messenger function within microvessel endothelial cells and possibly
      attached pericytes.

PMID- 9566592
TI  - Alteration of enzymatic activities implicating neuronal degeneration in the
      spinal cord of the motor neuron degeneration mouse during postnatal development.
AB  - Oxidative stress is suggested as a significant causative factor for pathogenesis
      of neuronal degeneration on spinal cord of human ALS. We measured some enzymic
      activities implicating neuronal degeneration process, such as cytochrome c
      oxidase (CO), superoxide dismutase (SOD), and transglutaminase (TG) in spinal
      cord of an animal model of ALS, motor neuron degeneration (Mnd) mouse, a mutant
      that exhibits progressive degeneration of lower spinal neurons during
      developmental growth, and compared them with age-matched control C57BL/6 mice. CO
      activity in Mnd spinal cord decreased during early postnatal period, while SOD
      activity reduced in later stage. In Mnd tissue, TG activity in lumbar cord was
      increasing during early stage, but tended to decline in later period gradually.
      These biochemical alterations became evident prior to the appearance of clinical
      motor dysfunction which were observed in later stages of development in Mnd
      spinal cord.

PMID- 9566593
TI  - Release of endogenous glutamate, aspartate, GABA, and taurine from hippocampal
      slices from adult and developing mice under cell-damaging conditions.
AB  - The releases of endogenous glutamate, aspartate, GABA and taurine from
      hippocampal slices from 7-day-, 3-, 12-, and 18-month-old mice were investigated
      under cell-damaging conditions using a superfusion system. The slices were
      superfused under hypoxic conditions in the presence and absence of glucose and
      exposed to hydrogen peroxide. In the adult hippocampus under normal conditions
      the basal release of taurine was highest, with a response only about 2-fold to
      potassium stimulation (50 mM). The low basal releases of glutamate, aspartate,
      and GABA were markedly potentiated by K+ ions. In general, the release of the
      four amino acids was enhanced under all above cell-damaging conditions. In
      hypoxia and ischemia (i.e., hypoxia in the absence of glucose) the release of
      glutamate, aspartate and GABA increased relatively more than that of taurine, and
      membrane depolarization by K+ markedly potentiated the release processes. Taurine
      release was doubled in hypoxia and tripled in ischemia but K+ stimulation was
      abolished. In both the mature and immature hippocampus the release of glutamate
      and aspartate was greatly enhanced in the presence of H2O2, that of aspartate
      particularly in developing mice. In the immature hippocampus the increase in
      taurine release was 10-fold in hypoxia and 30-fold in ischemia, and potassium
      stimulation was partly preserved. The release processes of the four amino acids
      in ischemia were all partially Ca2+-dependent. High concentrations of excitatory
      amino acids released under cell-damaging conditions are neurotoxic and contribute
      to neuronal death during ischemia. The substantial amounts of the inhibitory
      amino acids GABA and taurine released simultaneously may constitute an important
      protective mechanism against excitatory amino acids in excess, counteracting
      their harmful effects. In the immature hippocampus in particular, the massive
      release of taurine under cell-damaging conditions may have a significant function
      in protecting neural cells and aiding in preserving their viability.

PMID- 9566595
TI  - Sexually dimorphic activation of liver and brain phosphatidylethanolamine N
      methyltransferase by dietary choline deficiency.
AB  - Phosphatidylethanolamine N-methyltransferase (PEMT) activity was measured by a
      radioenzymatic assay in homogenates of brain and liver obtained from Sprague
      Dawley rats fed a choline-free or control (0.3 g/kg of choline chloride) diet for
      seven days. Choline deficiency increased PEMT activity in the liver of male rats
      by 34% but had no effect on hepatic PEMT in females. In contrast, brain PEMT
      activity was increased in brain of choline deficient females (by 49%) but was
      unaltered in males. Activation of the PE methylation pathway in female brain may
      constitute a compensatory mechanism to sustain PC synthesis during choline
      deficiency.

PMID- 9566594
TI  - Cannabinoid receptors and their endogenous agonist, anandamide.
AB  - Cannabinoids are a class of compound found in marijuana which have been known for
      their therapeutic and psychoactive properties for at least 4000 years. Isolation
      of the active principle in marijuana, delta9-THC, provided the lead structure in
      the development of highly potent congeners which were used to probe for the
      mechanism of marijuana action. Cannabinoids were shown to bind to selective
      binding sites in brain tissue thereby regulating second messenger formation. Such
      studies led to the cloning of three cannabinoid receptor subtypes, CB1, CB2, and
      CB1A all of which belong to the superfamily of G protein-coupled plasma membrane
      receptors. Analogous to the discovery of endogenous opiates, isolation of
      cannabinoid receptors provided the appropriate tool to isolate an endogenous
      cannabimimetic eicosanoid, anandamide, from porcine brain. Recent studies
      indicate that anandamide is a member of a family of fatty acid ethanolamides that
      may represent a novel class of lipid neurotransmitters. This review discusses
      recent progress in cannabinoid research with a focus on the receptors for delta9
      THC, their coupling to second messenger responses, and the endogenous lipid
      cannabimimetic, anandamide.

PMID- 9566596
TI  - Kinetic analysis in mixed micelles of partially purified rat brain phospholipase
      D activity and its activation by phosphatidylinositol 4,5-bisphosphate.
AB  - A partially purified rat brain membrane phospholipase D (PLD) activity was
      characterized in a mixed micellar system consisting of 1-palmitoyl-2-[6-N-(7
      nitrobenzo-2-oxa-1,3-diazol-4-yl)-amino]capr oyl-phosphatidylcholine (NBD-PC) and
      Triton X-100, under conditions where Triton X-100 has a surface dilution effect
      on PLD activity and the catalytic rate is dependent on the surface concentration
      (expressed in terms of molar ratio) of NBD-PC. PLD activity was specifically
      activated by phosphatidylinositol 4,5-bisphosphate (PIP2), and the curve of
      activation versus PIP2 molar ratio fitted a Michaelis-Menten equation with a
      K(act) value between molar ratios of 0.001-0.002. Maximal activation was observed
      at a PIP2 molar ratio of 0.01. Similar values were obtained when activities of
      partially purified PLD as well as membrane-bound PLD were determined towards pure
      NBD-PC micelles. In the mixed micellar system PIP2 was shown to elevate by 6-22
      fold the specificity constant of PLD towards NBD-PC (K(A), which is proportional
      to Vmax/Km). Kinetic analysis of PLD trans-phosphatidylation activity towards
      ethanol, 1-propanol and 1-butanol revealed a Michaelis-Menten type dependence on
      alcohol concentration up to 1000, 200 and 80 mM, respectively. While Vmax values
      were similar towards all three alcohols, enzyme affinity increased as the alcohol
      was longer, and Km values for ethanol, 1-propanol and 1-butanol were 291, 75 and
      16 mM (respectively). PLD specificity constants (K(A)) towards ethanol, 1
      propanol and 1-butanol were shown to be respectively 260, 940 and 5,920 times
      higher than to water, the competing substrate. 1-Propanol and 1-butanol inhibited
      PLD activity above 400 and 100 mM, respectively. The present results indicate
      that partially purified PLD obeys surface dilution kinetics with regard to its
      phospholipid substrate PC and its cofactor PIP2, and that in the presence of
      alcohols, its transphosphatidylation activity may be analyzed as a competitive
      reaction to the hydrolysis reaction.

PMID- 9566597
TI  - In vitro stimulation of protein kinase C by melatonin.
AB  - It has been shown that melatonin through binding to calmodulin acts both in vitro
      and in vivo as a potent calmodulin antagonist. It is known that calmodulin
      antagonists both bind to the hydrophobic domain of Ca2+ activated calmodulin, and
      inhibit protein kinase C activity. In this work we explored the effects of
      melatonin on Ca2+ dependent protein kinase C activity in vitro using both a pure
      commercial rat brain protein kinase C, and a partially purified enzyme from MDCK
      and N1E-115 cell homogenates. The results showed that melatonin directly
      activated protein kinase C with a half stimulatory concentration of 1 nM. In
      addition the hormone augmented by 30% the phorbol ester stimulated protein kinase
      C activity and increased [3H] PDBu binding to the kinase. In contrast, calmodulin
      antagonists (500 microM) and protein kinase C inhibitors (100 microM) abolished
      the enzyme activity. Melatonin analogs tested were ineffective in increasing
      either protein kinase C activity or [3H] PDBu binding. Moreover, the hormone
      stimulated protein kinase C autophosphorylation directly and in the presence of
      phorbol ester and phosphatidylserine. The results show that besides the melatonin
      binding to calmodulin, the hormone also interacts with protein kinase C only in
      the presence of Ca2+. They also suggest that the melatonin mechanism of action
      may involve interactions with other intracellular hydrophobic and Ca2+ dependent
      proteins.

PMID- 9566599
TI  - Dietary saturated fatty acids and brain function.
AB  - The degree to which fatty acids modulate brain function beyond periods of rapid
      brain growth is poorly understood. Nevertheless, recent evidence suggests that
      dietary fatty acid composition influences numerous behaviors including body
      temperature regulation, pain sensitivity, feeding behavior including
      macronutrient selection, and cognitive performance. Importantly, alterations are
      observed in the absence of essential fatty acid (EFA) deficiency, beyond periods
      of rapid brain development, and at levels similar to those consumed by the North
      American population. Data suggest that the content of saturated fatty acids
      (SFAs), and not that of the EFAs, may be the important component of dietary fat
      mediating macronutrient selection and cognition under these experimental
      conditions. Yet, a direct role of SFAs in modulating brain functions has not been
      elucidated. A discussion of potential mechanisms which may directly involve the
      central nervous system, or may indirectly influence central processes via
      peripheral pathway(s) is presented.

PMID- 9566598
TI  - The rhythmic GABAergic system.
AB  - GABA is the major inhibitory neurotransmitter in the mammalian brain, and has
      been implicated in the regulation of a variety of behavioral functions, including
      biological rhythms. The focus of this minireview is the rhythmic variation of the
      central GABAergic system, comprising fluctuations of GABA levels and turnover,
      GABA receptor affinity and postsynaptic activity on the chloride ionophore in
      rodent's brain. Neurochemical rhythms correlated with diurnal and circadian
      changes in several behaviors associated with the GABA(A) receptor, e.g.,
      anxiolysis-related behavior. GABA is considered to be the principal
      neurotransmitter of the mammalian circadian system, being present in the
      suprachiasmatic nuclei and the intergeniculate leaflet. Pharmacological
      manipulations of GABA(A) receptors phase shift circadian rhythms and alter
      circadian responses to light. Administration of putative modulators of GABA
      function, like melatonin or neuroactive steroids, affects the timing of
      biological rhythms. Therefore, not only does the GABAergic system exhibit strong
      diurnal and circadian variations, but it also serves as one of the key modulators
      of the circadian apparatus.

PMID- 9566600
TI  - Modulation of learning and neuronal membrane composition in the rat by essential
      fatty acid preparation: time-course analysis.
AB  - Previous studies have shown that chronic administration of SR-3 (a 1:4 mixture of
      alpha-linolenic and linoleic acid) affects spatial learning, thermoregulation,
      pain threshold and protection from seizures. The mode of action is unknown. One
      possible explanation is that the preparation induces changes in the fatty acids
      profile and in the cholesterol level in the neuronal membrane. This study used 15
      independent groups of rats (n = 12) which were given either saline, mineral oil
      (vehicle) or SR-3 (25 mg/kg) for 0, 1, 2, 3, or 4 weeks. The learning performance
      was measured in the Morris Water tank and the fatty acids profile and the
      cholesterol level were examined by the GC method in synaptosomes obtained from
      the frontal cortex of the rats. SR-3 improved the learning performance and
      induced major changes in the neuronal membrane composition, such as an increase
      in the total level of fatty acids, an increase in the level of essential fatty
      acids and a decrease in the cholesterol level. Those changes occurred after 3
      weeks of treatment. The biochemical variables can predict the behavioral
      variables but not vice versa. The changes in the neuronal membrane may result in
      a modification of the membrane fluidity, which may, in turn, enhance cognitive
      and neuropharmacological effects.

PMID- 9566601
TI  - Blood-brain barrier carrier-mediated transport and brain metabolism of amino
      acids.
AB  - The transport of neutral amino acids through the brain capillary endothelial
      wall, which makes up the blood-brain barrier (BBB) in vivo, is an important
      control point for the overall regulation of cerebral metabolism, including
      protein synthesis and neurotransmitter production. The Michaelis-Menten kinetics
      of BBB amino acid transport have been investigated in vivo with the brain uptake
      index (BUI) technique, and in vitro with the isolated human brain capillary
      preparation. The only amino acid that is albumin-bound is tryptophan, and the
      majority of albumin-bound tryptophan in the plasma is available for transport
      through the BBB via an enhanced dissociation mechanism that operates at the
      surface of the brain capillary endothelium. The availability in brain of amino
      acids is predicted from the BBB Km values to be sharply influenced by supra
      physiological concentrations of phenyalanine in the 200-500 microM range.
      Moreover, the measurement of cerebral protein synthesis with an internal carotid
      artery perfusion technique and HPLC-based measurements of aminoacyl-transfer RNA
      specific activities shows an inverse relationship between cerebral protein
      synthesis and plasma phenyalanine concentrations in the 200-500 microM range.
      These findings indicate the neurotoxicity of hyperphenylalninemia is not
      restricted to the phenylketonuria range of approximately 2000 microM, but is
      exerted in the supra-physiological range of 200-500 microM.

PMID- 9566602
TI  - Effects of dexamethasone in vivo and in vitro on hexose transport in brain
      microvasculature.
AB  - Glucocorticoids induce hyperinsulinemia, hyperglycemia, and depress glucose
      transport by aortic endothelium. High glucocorticoid doses are used for many
      diseases, but with unknown effects on brain glucose transport or metabolism. This
      study tested the hypothesis that glucocorticoids affect glucose transport or
      metabolism by brain microvascular endothelium. Male rats received dexamethasone
      (DEX) s.c. with sucrose feeding for up to seven days. Cerebral microvessels from
      rats treated with DEX/sucrose demonstrated increased GLUT1 and brain glucose
      extraction compared to controls. Glucose transport in vivo correlated with
      hyperinsulinemia. Pre-treatment with low doses of streptozotocin blunted
      hyperinsulinemia and prevented increased glucose extraction induced by DEX. In
      contrast, isolated brain microvessels exposed to DEX in vitro demonstrated
      suppression of 2-deoxyglucose uptake and glucose oxidation. We conclude that
      DEX/sucrose treatment in vivo increases blood-brain glucose transport in a manner
      that requires the effects of chronic hyperinsulinemia. These effects override any
      direct inhibitory effects of either hyperglycemia or DEX.

PMID- 9566604
TI  - Altered tryptophan metabolism in mice with herpes simplex virus encephalitis:
      increases in spinal cord quinolinic acid.
AB  - Mice infected with the herpes simplex virus, type-1, developed a paralysis which
      was associated with increased levels of the neurotoxin quinolinic acid (QUIN).
      The largest increases in QUIN were observed in the spinal cord with much smaller
      changes in the rostral forebrain or serum. The time course for the paralysis
      coincided with the increase in spinal cord QUIN, a maximal 40-fold elevation, at
      7-10 days post infection. The time course suggested that the increases in QUIN
      were due to its local synthesis. Consistent with this possibility, herpes virus
      infected mice had increased activities of indoleamine 2,3-dioxygenase and
      kynurenine hydroxylase (two key enzymes in QUIN formation), when compared to non
      infected controls. Since QUIN is formed by activated macrophages, these new data
      are consistent with QUIN formation as part of the host response to a pathogen
      whose importance is discussed.

PMID- 9566603
TI  - The central 5-HT3 receptor in CNS disorders.
AB  - Among the characterized 5-HT receptors of the central nervous system, the type 3
      receptor subtype (5-HT3R) is the only one known to be a ligand-gated ion channel.
      Its early pharmacological characterization and mapping by radioligand binding
      autoradiography suggested that this receptor may, among other actions, regulate
      dopamine release in the nigro-striatal pathway and reduce alcohol consumption in
      experimental animals while antagonists of this receptor have been reported to
      treat anxiety disorders. Following the cloning of this receptor in 1991, direct
      cellular localization was made possible by in situ hybridization and
      immunohistochemical analysis. Here we summarize our recent efforts showing that 5
      HT3R-expressing neurons are mainly GABA containing cells in the rat neocortex,
      olfactory cortex, hippocampus, and amygdala which also often contain
      cholecystokinin (CCK) immunoreactivity. These results provide a means to unify
      some of the initial pharmacological observations.

PMID- 9566605
TI  - Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal
      dopamine release in conscious rats.
AB  - Theanine, r-glutamylethylamide, is one of the major components of amino acids in
      Japanese green tea. Effect of theanine on brain amino acids and monoamines, and
      the striatal release of dopamine (DA) was investigated. Determination of amino
      acids in the brain after the intragastric administration of theanine showed that
      theanine was incorporated into brain through blood-brain barrier via leucine
      preferring transport system. The concentrations of norepinephrine, 3,4
      dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the
      brain regions were unaffected by the theanine administration except in striatum.
      Theanine administration caused significant increases in serotonin and/or DA
      concentrations in the brain, especially in striatum, hypothalamus and
      hippocampus. Direct administration of theanine into brain striatum by
      microinjection caused a significant increase of DA release in a dose-dependent
      manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the
      theanine-induced DA release. Pretreatment with the Ringer buffer containing an
      antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1
      hr did not change the significant increase of DA release induced by theanine.
      However, in the case of pretreatment with AP-5, (+/-)-2-amino-5
      phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine
      induced DA release from striatum was significantly inhibited. These results
      suggest that theanine might affect the metabolism and/or the release of some
      neurotransmitters in the brain, such as DA.

PMID- 9566607
TI  - Protection against developmental deficiencies by a lipophilic VIP analogue.
AB  - Stearyl-Nle-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP)
      exhibiting a 100-fold greater potency than the parent molecule and specificity
      for a receptor associated with neuronal survival. Here, the developmental and
      protective effects of SNV were investigated in vivo using two models of
      developmental retardation, hypoxia and cholinergic blockade. In both cases
      chronic administration of SNV during development provided protective effects.
      Water maze experiments on the weaned animals have demonstrated a prophylactic
      action for SNV and enhancement of spatial memory in animals exposed to a
      cholinotoxin. SNV may act by providing neuroprotection, thereby improving
      cognitive functions. This work is dedicated to Prof. R.J. Wurtman whose
      inspiration and leadership in the field of neuroscience and cognition is beyond
      comparison.

PMID- 9566608
TI  - Vasopressinergic, oxytocinergic, and somatostatinergic neuronal activity after
      adrenalectomy and immobilization stress.
AB  - Twenty days after bilateral adrenalectomy (ADX) or immediately after the last of
      three 6-h long immobilization periods, the levels of hypothalamic and
      neurohypophyseal L-[35S]Cys-labeled arginine vasopressin (AVP), oxytocin (OT),
      and somatostatin-14 (SRIF) (only stressed animals) were measured simultaneously
      in male Wistar rats, after third ventricular administration of the labeled
      precursor, via guide-cannulae. The acetic acid-extracted labeled peptide
      fractions were purified by two sequential HPLC steps. After a 4 h period of
      labeling, only L-[35S]Cys-AVP was selectively increased in the hypothalami of ADX
      ized rats, compared to the sham-operated animals, possibly reflecting a
      significant activation of the paraventricular parvocellular (PVC)
      AVP/corticotropin-releasing factor (CRF) neurons. The increased accumulation of
      neurohypophyseal L-[35S]Cys-labeled AVP and OT in these animals, without changes
      in the endogenous levels of these peptides, as measured by UV absorbance, also
      suggests a moderate activation of the magnocellular (MGC) AVP and OT neurons, as
      a consequence of adrenal insufficiency. In response to immobilization stress,
      levels of L-[35S]Cys-OT were selectively increased in the hypothalami and
      corresponding neurohypophyses, 2 h and 4 h after receiving the label,
      concomitantly with a statistically significant reduction in the stores of OT in
      the neural lobes. AVP and SRIF biosynthesis remained unaffected by
      immobilization; the neurohypophyseal AVP stores likewise remained unchanged.
      These observations suggest the selective activation of MGC-OT neurons in response
      to chronic immobilization stress. Selective increases in hypothalamic L-[35S]Cys
      AVP in ADX-ized rats, and in hypothalamic L-[35S]Cys-OT in chronically stress
      immobilized rats, are presented as a measure of PVC-AVP/CRF and MGC-OT neuronal
      activation, respectively.

PMID- 9566609
TI  - Cryptic expression of the 70-kDa heat shock protein, hsp72, in gerbil hippocampus
      after transient ischemia.
AB  - The 70 kDa heat shock protein, hsp72, is known to be induced following transient
      global ischemia in brain, as detected by immunocytochemistry and in situ
      hybridization techniques. However, while hsp72 mRNA is expressed rapidly
      following postischemic recirculation, immunocytochemistry fails to detect hsp72
      protein for many hours after such insults, even in cell populations that readily
      express Fos and other proteins encoded by ischemia-induced mRNAs. In the present
      study, hsp72 expression in gerbil hippocampus was compared by immunocytochemistry
      and immunoblot methods at several intervals following 10 min ischemia. As
      established in previous studies, hsp72 immunoreactivity remained undetectable in
      postischemic neurons at 6 h following such insults. In contrast, immunoblots of
      dissected gerbil hippocampus demonstrated nearly maximal accumulation of hsp72 at
      this time point. These results indicate that the protein is present, but cryptic
      to detection in perfusion-fixed sections, during early recirculation. The
      constitutively expressed heat shock cognate protein, hsc70, did not show
      significant changes in level or distribution by either method, except for a
      decrease in CA1 staining at 48 h. These results confirm that hsp72 rapidly
      accumulates to high levels in postischemic hippocampus, and suggest that further
      studies of its subcellular localization during this interval may offer insight
      into its functional role as a component of the stress response in neurons after
      such insults.

PMID- 9566610
TI  - In vitro reconstitution of neurotransmitter release.
AB  - The vesicular hypothesis has stimulated fruitful investigations on many secreting
      systems. In the case of rapid synaptic transmission, however, the hypothesis has
      been found difficult to reconcile with a number of well established observations.
      Brief impulses of transmitter molecules (quanta) are emitted from nerve terminals
      at the arrival of an action potential by a mechanism which is under the control
      of multiple regulations. It is therefore not surprising that quantal release
      could be disrupted by experimental manipulation of a variety of cellular
      processes, such as a) transmitter uptake, synthesis, or transport, b) energy
      supply, c) calcium entry, sequestration and extrusion, d) exo- or endocytosis, e)
      expression of vesicular and plasmalemmal proteins, f) modulatory systems and
      second messengers, g) cytoskeleton integrity, etc. Hence, the approaches by
      "ablation strategy" do not provide unequivocal information on the final step of
      the release process since there are so many ways to stop the release. We propose
      an alternate approach: the "reconstitution strategy". To this end, we developed
      several preparations for determining the minimal system supporting Ca2+-dependent
      transmitter release. Release was reconstituted in proteoliposomes, Xenopus
      oocytes and transfected cell lines. Using these systems, it appears that a
      presynaptic plasmalemmal proteolipid, that we called mediatophore should be
      considered as a key molecule for the generation of transmitter quanta in natural
      synapses.

PMID- 9566611
TI  - Age-related alterations in pre-synaptic and receptor-mediated cholinergic
      functions in rat brain.
AB  - Fractional [3H]acetylcholine (ACh) release and regulation of release process by
      muscarinic receptors were studied in corpus striatum of young and aged rat
      brains. [3H] Quinuclidinyl benzilate (QNB) binding and carbachol stimulated
      phosphoinositide turnover, on the other hand, were compared in striatal,
      hippocampal and cortical tissues. High potassium (10 mM)-induced fractional
      [3H]ACh release from striatal slices was reduced by aging. Although inhibition of
      acetylcholinesterase with eserine (20 microM) significantly decreased stimulation
      induced fractional [3H]ACh release in two groups of rats, this inhibition
      slightly lessened with aging. Incubation of striatal slices with muscarinic
      antagonists reversed eserine-induced inhibition in fractional [3H]ACh release
      with a similar order of potency (atropine = 4-DAMP > AF-DX 116 > pirenzepine) in
      young and aged rat striatum, but age-induced difference in stimulated ACh release
      was not abolish by muscarinic antagonists. These results suggested that
      fractional [3H]ACh release from striatum of both age groups is modulated mainly
      by M3 muscarinic receptor subtype. Although both muscarinic receptor density and
      labeling of inositol lipids with [myo-3H]inositol decreased with aging, carbachol
      stimulated [3H]myo inositol-1-fosfat (IP1) accumulation was found similar in
      striatal, cortical and hippocampal slices.

PMID- 9566606
TI  - Gonadal steroids and neuronal function.
AB  - Gonadal steroid hormones may affect, simultaneously, a wide variety of neuronal
      targets, influencing the way the brain reacts to many external and internal
      stimuli. Some of the effects of these hormones are permanent, whereas others are
      short lasting and transitory. The ways gonadal steroids affect brain function are
      very versatile and encompass intracellular, as well as, membrane receptors. In
      some cases, these compounds can interact with several neurotransmitter systems
      and/or transcription factors modulating gene expression. Knowledge about the
      mechanisms implicated in steroid hormone action will facilitate the understanding
      of brain sexual dimorphism and how we react to the environment, to drugs, and to
      certain disease states.

PMID- 9566612
TI  - Decreased serum choline concentrations in humans after surgery, childbirth, and
      traumatic head injury.
AB  - The serum levels of choline decreased by approximately 50% in patients having a
      surgery under general as well as epidural anesthesia. The decrease is lasts for
      two days after surgery. Intravenous administration of succinylcholine, either by
      a single bolus injection or by a slow continuous infusion, increased the serum
      choline levels several folds during surgery. In these patients, a significant
      decrease in the serum choline levels was observed one and two days after surgery.
      In 16 pregnant women at the term, serum choline levels were higher than the value
      observed in 19 nonpregnant women. The serum choline levels decreased by about 40%
      or 60% after having a childbirth either by vaginal delivery or caesarean section,
      respectively. Serum choline levels in blood obtained from 9 patients with
      traumatic head injury were significantly lower than the observed levels in blood
      samples obtained from healthy volunteers. These observations show that serum
      choline levels increase during pregnancy and decrease during stressful situations
      in humans.

PMID- 9566613
TI  - Choline administration reverses hypotension in spinal cord transected rats: the
      involvement of vasopressin.
AB  - Intracerebroventricular (i.c.v.) choline (50-150 microg) increased blood pressure
      and decreased heart rate in spinal cord transected, hypotensive rats. Choline
      administered intraperitoneally (60 mg/kg), also, increased blood pressure, but to
      a lesser extent. The pressor response to i.c.v. choline was associated with an
      increase in plasma vasopressin. Mecamylamine pretreatment (50 microg; i.c.v.)
      blocked the pressor, bradycardic and vasopressin responses to choline (150
      microg). Atropine pretreatment (10 microg; i.c.v.) abolished the bradycardia but
      failed to alter pressor and vasopressin responses. Hemicholinium-3 [HC-3 (20
      microg; i.c.v.)] pretreatment attenuated both bradycardia and pressor responses
      to choline. The vasopressin V1 receptor antagonist, (beta-mercapto-beta,beta
      cyclopenta-methylenepropionyl1, O-Me-Tyr2, Arg8)-vasopressin (10 microg/kg)
      administered intravenously 5 min after choline abolished the pressor response and
      attenuated the bradycardia-induced by choline. These data show that choline
      restores hypotension effectively by activating central nicotinic receptors via
      presynaptic mechanisms, in spinal shock. Choline-induced bradycardia is mediated
      by central nicotinic and muscarinic receptors. Increase in plasma vasopressin is
      involved in cardiovascular effects of choline.

PMID- 9566614
TI  - AF64A-induced changes in N-myc expression in the LA-N-2 human neuroblastoma cell
      line are modulated by choline and hemicholinium-3.
AB  - Due to AF64A's structural similarity to choline, AF64A can selectively affect
      cholinergic neurons, which possess a high affinity choline transport system for
      acetylcholine synthesis. The mechanism by which AF64A selectively produces its
      cytotoxic effect is unknown. However, based on previous studies that demonstrate
      that DNA lesions produced by AF64A caused premature termination of N-myc
      transcription in vitro, it is possible that AF64A may affect the transcription of
      genes necessary for developmental maintenance in cholinergic cells. Using the LA
      N-2 cells as a model to study the effects of AF64A in a purely cholinergic
      system, we investigated the effects of AF64A on the expression of the N-myc gene
      and monitored cell growth. AF64A produced a maximal decrease in N-myc mRNA with a
      return to steady state levels at later time points. Moreover, a decrease in cell
      numbers in AF64A-treated cells was observed, and these cells did not double in
      number at their respective doubling time as compared to control. In other
      studies, a causal relationship between a reduction in N-myc and an inhibition of
      cell growth and replication has been reported. While these studies do not allow
      us to conclude that AF64A is specific for N-myc, the data do, nevertheless,
      suggest that AF64A affects cell growth and/or replication by down-regulating the
      expression of N-myc which is involved in differentiation and cell growth in
      neuroblastomas. Presence of choline or hemicholinium-3 prevented the AF64A
      induced decrease of N-myc levels by competing with, or inhibiting the choline
      transport mechanism by which AF64A enters the cell, respectively.

PMID- 9566615
TI  - Choline availability modulates the expression of TGFbeta1 and cytoskeletal
      proteins in the hippocampus of developing rat brain.
AB  - Choline availability influences long-term memory in concert with changes in the
      spatial organization and morphology of septal neurons, however little is known
      concerning the effects of choline on the hippocampus, a region of the brain also
      important for memory performance. Pregnant rats on gestational day 12 were fed a
      choline control (CT), choline supplemented (CS), or choline deficient (CD) diet
      for 6 days and fetal brain slices were prepared on embryonic day 18 (E18). The
      hippocampus in these brain slices was studied for the immunohistochemical
      localization of the growth-related proteins transforming growth factor beta type
      1 (TGFbeta1) and GAP43, the cytoskeletal proteins vimentin and microtubule
      associated protein type 1 (MAP1), and the neuronal cell marker neuron specific
      enolase (NSE). In control hippocampus, there was weak expression of TGFbeta1 and
      vimentin proteins, but moderately intense expression of MAP1 protein. These
      proteins were not homogeneously distributed, but were preferentially localized to
      cells with large cell bodies located in the central (approximately CA1-CA3)
      region of the hippocampus, and to the filamentous processes of small cells in the
      fimbria region. Feeding a choline-supplemented diet decreased, whereas a choline
      deficient diet increased the intensity of immunohistochemical labeling for these
      proteins in E18 hippocampus. GAP43 and NSE were localized to peripheral nervous
      tissue but not hippocampus, indicating that the maturation of axons and neurite
      outgrowth in embryonic hippocampus were unaffected by the availability of choline
      in the diet. These data suggest that the availability of choline affects the
      differentiation of specific regions of developing hippocampus.

PMID- 9566616
TI  - Neuronal death: is there a role for astrocytes?
AB  - Astrocytes are ubiquitous in the brain and have multiple functions. It is
      becoming increasingly clear that they play an important role in monitoring the
      neuromicroenvironment in CNS and in information processing or signaling in the
      nervous system in normal conditions and respond to CNS injuries in a gradual and
      varied way. It is still debated whether such reactions are beneficial or
      detrimental. It was believed that reactive astrogliosis observed in most
      neurological disorders may regulate the removal of toxic compounds produced by
      damaged neurons and support neuronal growth by releasing trophic factors. However
      it was also suggested that astrocytes contribute to a decline of neurologic
      function, for example by accumulation and release of excitotoxic aminoacids after
      ischemia and oxidative stress, formation of epileptogenic scars in response to
      CNS injury and metabolism of protoxins to potent toxins. In a number of metabolic
      diseases astrocytes, not neurons, may be the primary target. The astrocyte's role
      in normal and pathological conditions will be discussed in the light of recent
      information about their metabolism, receptor distribution and release.

PMID- 9566618
TI  - NGF gene expression in dividing and non-dividing cells from AAV-derived
      constructs.
AB  - NGF expression in COS cells when driven by pTR.NGF (CMV promoter, AAV TRs) was
      more effective than either pc.NGF (CMV promoter, no AAV TRs) or dlk.NGF (AAV
      promoters and TRs). This NGF was able to differentiate PC12 cells. Differentiated
      PC12 cells transfected with pTR.NGF released NGF into medium. The fraction of
      pTR.NGF transfected PC12 cells that extended neurite-like processes 7 days post
      transfection was similar to the transfection efficiency, suggesting that
      transfected cells were selectively differentiated by locally released NGF.
      pTR.NGF-transfected primary cultures of either neurons or glia did not express
      exogenous NGF. These results indicate that NGF can be released by dividing and
      non-dividing cells, but not neonatally derived brain cells.

PMID- 9566617
TI  - Expression of cell cycle-related genes during neuronal apoptosis: is there a
      distinct pattern?
AB  - An emerging hypothesis considers the process of neuronal apoptosis as a
      consequence of unscheduled and unsynchronized induction of cell cycle mediators.
      Induction of several cell cycle genes precedes neuronal apoptosis and may be
      involved in determination of cell fate. We have now characterized changes in
      expression of cell cycle genes during apoptosis induced by oxidative stress in
      chick post-mitotic sympathetic neurons. Induction of cyclin B occurred prior to
      the commitment of neurons to both dopamine- and peroxide-triggered apoptosis.
      Both the neuronal death and the rise in cyclin B were inhibited by antioxidant
      treatment, suggesting a functional role for cyclin B induction during neuronal
      apoptosis. Induction of the cyclin dependent kinase CDK5 protein coincided with
      the time point when neurons were irreversibly committed to die. Expression of
      other cell cycle mediators such as cyclin D1 and the cyclin dependent kinases
      CDC2 and CDK2 was undetected and not induced by exposure to oxidative stress.
      Comparative analysis of the profile of cell cycle mediators induced during
      neuronal apoptosis of different neuronal cell populations revealed no distinct
      pattern of events. There are no cell cycle stage-specific mediators that are
      ultimately stimulated during neuronal apoptosis, suggesting that multiple
      pathways of re-activating the dormant cell-cycle, converge to determine entry
      into apoptosis. Nevertheless, the existence of some cell cycle mediators, that
      were not reported so far to be induced in post mitotic neurons during oxidative
      stress, substantiate them as part of the strong differentiating forces.

PMID- 9566619
TI  - The cognitive psychopharmacology of Alzheimer's disease: focus on cholinergic
      systems.
AB  - The primary pathology in Alzheimer's disease (DAT) occurs in the basal forebrain
      cholinergic system (BFCS), which provides the major cholinergic innervation to
      the neocortex, hippocampus and amygdala. Consistent with the 'cholinergic
      hypothesis' of dementia in DAT, the most effective treatments so far developed
      for DAT are drugs which act to boost the functions of the BFCS. These include the
      centrally acting cholinesterase inhibitor tacrine, and the cholinergic agonist
      nicotine, acute administration of which leads to an improvement in attentional
      functions, in line with recent animal studies of the role of the BFCS in
      cognition. We conclude that future research should include the development of
      more potent, longer-lasting, less toxic cholinergic agents, which appear to be
      the best candidates for alleviating the cognitive symptomatology of DAT. Such
      drugs may also be useful in the treatment of a number of other cognitive
      disorders, including Lewy body dementia, attention deficit/hyperactivity
      disorder, and schizophrenia.

PMID- 9566622
TI  - Use of a hemoglobin-trapping approach in the determination of nitric oxide in in
      vitro and in vivo systems.
AB  - We describe methods for measuring the release of nitric oxide (NO) derived from
      organic nitrates in vitro, using triple wavelength and difference
      spectrophotometry in the presence and absence of concentric microdialysis probes.
      These methods are based on the ability of NO to oxidize oxyhemoglobin (OxyHb) to
      methemoglobin (MetHb) quantitatively in aqueous solution. Isosorbide dinitrate
      (ISDN), a thiol-dependent organic nitrate, increased MetHb concentration in 45
      min from 2.47 +/- 0.47 to 4.15 +/- 0.12 microM (p < 0.05) and decreased OxyHb
      concentration from 2.13 +/- 0.35 to 0.33 +/- 0.26 microM (p < 0.05) at 37 degrees
      C. At 27 degrees C, the OxyHb concentration was not significantly altered (2.04
      +/- 0.23 to 1.60 +/- 0.04 microM) by ISDN, nor was the MetHb concentration (from
      2.68 +/- 0.50 to 2.59 +/- 0.25 microM). Sodium nitroprusside (SNP), a thiol
      independent organic nitrate, increased MetHb concentrations in 30 min from 4.21
      +/- 0.26 to 6.00 +/- 0.56 microM (p < 0.05) at 37 degrees C, and from 4.23 +/-
      0.39 to 5.90 +/- 0.43 microM (p < 0.01) at 27 degrees C. SNP also decreased OxyHb
      concentrations in 30 min from 1.99 +/- 0.32 to 0.13 +/- 0.12 microM (p < 0.01) at
      37 degrees C, and from 2.25 +/- 0.31 to 0.13 +/- 0.09 microM (p < 0.01) at 27
      degrees C. Difference spectrophometry indicated that 0.25-5 mM SNP significantly
      increased NO production in a dose-dependent fashion. This hemoglobin-trapping
      technique was also useful in quantifying the concentrations of NO released from
      SNP in aqueous solution in vitro, using concentric microdialysis probes. The NO
      concentration following exposure to SNP was 530 +/- 50 nM, as determined using
      the difference spectrophotometric technique. To demonstrate the applicability of
      this technique to in vivo microdialysis, we implanted concentric microdialysis
      probes into hippocampus and cerebellum of conscious and anesthetized rats.
      Baseline NO concentrations in hippocampus of conscious and anesthetized rats were
      11 +/- 2 nM and 23 +/- 9 nM, respectively, while in the cerebellum NO
      concentrations were 28 +/- 9 nM and 41 +/- 20 nM, respectively. These results
      demonstrate that microdialysis using a novel hemoglobin-trapping technique
      possesses adequate sensitivity to measure the NO levels produced from organic
      nitrates in aqueous solutions, and further document the applicability of this
      approach to in vivo systems.

PMID- 9566621
TI  - Vasopressin and bradykinin regulate secretory processing of the amyloid protein
      precursor of Alzheimer's disease.
AB  - The amyloid protein precursor (APP) can be processed via several alternative
      processing pathways. Alpha-secretase processing by cleavage within the amyloid
      beta-peptide domain of APP is highly regulated by several external and internal
      signals including G protein-coupled receptors, protein kinase C and phospholipase
      A2. In order to demonstrate that G protein-coupled neuropeptide receptors for
      bradykinin and vasopressin can increase alpha-secretase processing of APP, we
      stimulated endogenously expressed bradykinin or vasopressin receptors in cell
      culture with the neuropeptides and measured the secreted ectodomain (APPs) in the
      conditioned media. Both bradykinin and vasopressin rapidly increased
      phosphatidylinositol (PI) turnover in PC-12 and in NRK-49F cells, indicating that
      these cell lines constitutively expressed functional PI-linked receptors for
      these neuropeptides. Both bradykinin and vasopressin readily stimulated APPs
      secretion. Increased APPs secretion was concentration-dependent and saturable,
      and it was blocked by receptor antagonists indicating specific receptor
      interaction of the peptides. The bradykinin-induced increase in APPs secretion in
      PC-12 cells was mediated by protein kinase C (PKC), whereas vasopressin receptors
      in NRK-49F cells were coupled to APP processing by PKC-independent signalling
      pathways. Our data show that neuropeptides can modulate APP processing in cell
      culture. In as much as increased alpha-secretase processing is associated with
      decreased formation of A beta(1-40), a major constituent of amyloid plaques, our
      findings suggest a possible role for modulating neuropeptide receptors as a
      strategy for altering amyloid metabolism in Alzheimer's disease brain.

PMID- 9566623
TI  - Spontaneous EEG theta activity controls frontal visual evoked potential
      amplitudes.
AB  - Frontal visual evoked potentials (VEPs) were studied in order to extend the
      application of a recently introduced algorithm for selective averaging of evoked
      potentials. This algorithm is based on the inverse relationship between
      amplitudes of alpha or theta components of the spontaneous EEG activity and
      evoked potential (EP) amplitudes. Stimuli were only applied if the root mean
      square (RMS) value of the ongoing EEG at the lead F4 was below an individual
      threshold level ('selective stimulation'). For this comparison, the EEG was
      filtered in one of the frequency ranges 'alpha', 'theta' and 'alpha and theta',
      respectively. 'Alpha' and 'alpha-and-theta-dependent' selective stimulation
      conditions resulted in significant amplitude increases (P < 0.05) at the input
      reference channel F4 and partly at ipsihemispherical temporal and parietal leads
      and at Cz. The largest increase of 35% at F4 (P < 0.01) was obtained with visual
      stimulation during low prestimulus theta activity. We conclude that spontaneous
      theta activity of the frontal cortex may be a factor influencing the amplitudes
      of frontal VEPs. A sophisticated analysis of frontal EPs, mainly in the framework
      of cognitive studies, should consider the theta activity prior to stimulation.

PMID- 9566624
TI  - Localization of spatial attention processes with the aid of a probe technique.
AB  - A sudden visual onset is thought to 'attract attention to its location' within
      less than 100 ms. We attempted to measure the effect of this attentional process
      on the event-related potential (ERP) to a probe presented about 140 ms after the
      onset, and to delineate the spatiotemporal characteristics of such an effect, if
      any. ERPs were recorded from 30 channels from 6 subjects while they performed a
      target detection task. Both targets and probes could be located in each of the 4
      quadrants (eccentricities 6.1 degrees and 7 degrees, respectively). For a given
      single target, the subsequent probe was either presented near the location of the
      target ('valid target') or at the diagonal opposite ('invalid target').
      Appropriate 'neutral' conditions (probes preceded by no target, or by
      simultaneous targets in all quadrants) were applied, and ERPs to probes were
      corrected for the contribution of the ERPs to targets. The earliest effect of
      (in)validity was found at about 120 ms after probe onset for lower field probes.
      This effect consisted of enhanced posterior positivity for valid relative to
      neutral relative to invalid conditions. This positivity was superposed on a
      contralateral, extrastriate negative ongoing wave peaking at about 150 ms
      ('N150'). Source localization suggested that the (in)validity effects originate
      from deep medial parietal areas. The source corresponding to the N150 activity
      was not influenced by (in)validity. An earlier deflection to the probe at 80 ms
      ('NP80') depended on location, but not on (in)validity, and seemed to be of
      striate origin. Results are discussed in terms of a model postulating an
      attention-independent 'input module' from which activation is fed to a 'location
      module' embodying the actual attention mechanism.

PMID- 9566620
TI  - The role of the amyloid protein precursor (APP) in Alzheimer's disease: does the
      normal function of APP explain the topography of neurodegeneration?
AB  - Alzheimer's disease (AD) is the most common form of dementia in the aged
      population. Early-onset familial AD (FAD) involves mutations in a gene on
      chromosome 21 encoding the amyloid protein precursor or on chromosomes 14 or 1
      encoding genes known as presenilins. All mutations examined have been found to
      increase the production of amyloidogenic forms of the amyloid protein (A beta), a
      4 kDa peptide derived from APP. Despite the remarkable progress in elucidating
      the biochemical mechanisms responsible for AD, little is known about the normal
      function of APP. A model of how APP and A beta are involved in pathogenesis is
      presented. This model may explain why certain neuronal populations are
      selectively vulnerable in AD. It is suggested that those neurons which more
      readily undergo neuritic sprouting and synaptic remodelling are more vulnerable
      to A beta neurotoxicity.

PMID- 9566625
TI  - A method for the calculation of induced band power: implications for the
      significance of brain oscillations.
AB  - A method for the calculation of significant changes in induced band power (IBP)
      is presented. In contrast to traditional measures of event-related band power
      (ERBP) which are composed of evoked and not evoked EEG components, the proposed
      measure for IBP is deprived from phase locked (or evoked) EEG activity. It is
      assumed that changes in IBP reflect the modulation of brain oscillations that are
      largely independent from ERPs. The results of a visual oddball task show that
      significant changes in IBP can be observed in response to the presentation of a
      warning signal (preceding a target or nontarget) and the imperative stimulus
      (i.e. a target or nontarget) in the alpha, theta and delta band. Only a few
      significant changes in IBP were obtained for the warning signal in the theta band
      although highly significant changes in ERBP were found. Our findings document
      that changes in IBP may be considered a phenomenon that is largely independent
      from the occurrence of ERPs. They underline the significance of oscillatory
      processes and suggest that induced rhythms are modulated by stimuli and/or events
      in a not phase locked way.

PMID- 9566626
TI  - Auditory evoked potentials to abrupt pitch and timbre change of complex tones:
      electrophysiological evidence of 'streaming'?
AB  - Examination of the cortical auditory evoked potentials to complex tones changing
      in pitch and timbre suggests a useful new method for investigating higher
      auditory processes, in particular those concerned with 'streaming' and auditory
      object formation. The main conclusions were: (i) the N1 evoked by a sudden change
      in pitch or timbre was more posteriorly distributed than the N1 at the onset of
      the tone, indicating at least partial segregation of the neuronal populations
      responsive to sound onset and spectral change; (ii) the T-complex was
      consistently larger over the right hemisphere, consistent with clinical and PET
      evidence for particular involvement of the right temporal lobe in the processing
      of timbral and musical material; (iii) responses to timbral change were
      relatively unaffected by increasing the rate of interspersed changes in pitch,
      suggesting a mechanism for detecting the onset of a new voice in a constantly
      modulated sound stream; (iv) responses to onset, offset and pitch change of
      complex tones were relatively unaffected by interfering tones when the latter
      were of a different timbre, suggesting these responses must be generated
      subsequent to auditory stream segregation.

PMID- 9566627
TI  - Impaired mismatch negativity (MMN) generation in schizophrenia as a function of
      stimulus deviance, probability, and interstimulus/interdeviant interval.
AB  - Schizophrenia is a severe mental disorder associated with disturbances in
      perception and cognition. Event-related potentials (ERP) provide a mechanism for
      evaluating potential mechanisms underlying neurophysiological dysfunction in
      schizophrenia. Mismatch negativity (MMN) is a short-duration auditory cognitive
      ERP component that indexes operation of the auditory sensory ('echoic') memory
      system. Prior studies have demonstrated impaired MMN generation in schizophrenia
      along with deficits in auditory sensory memory performance. MMN is elicited in an
      auditory oddball paradigm in which a sequence of repetitive standard tones is
      interrupted infrequently by a physically deviant ('oddball') stimulus. The
      present study evaluates MMN generation as a function of deviant stimulus
      probability, interstimulus interval, interdeviant interval and the degree of
      pitch separation between the standard and deviant stimuli. The major findings of
      the present study are first, that MMN amplitude is decreased in schizophrenia
      across a broad range of stimulus conditions, and second, that the degree of
      deficit in schizophrenia is largest under conditions when MMN is normally
      largest. The pattern of deficit observed in schizophrenia differs from the
      pattern observed in other conditions associated with MMN dysfunction, including
      Alzheimer's disease, stroke, and alcohol intoxication.

PMID- 9566628
TI  - The mismatch negativity for duration decrement of auditory stimuli in healthy
      subjects.
AB  - The amplitude and latency of the mismatch negativity (MMN) elicited by occasional
      shorter-duration tones (25 and 50 ms) in a sequence of 75 ms standard tones were
      studied in 40 healthy subjects (9-84 years). The replicability and age dependence
      of the MMN-responses were determined. The 25 ms deviant tone evoked a clear
      response in 39 of the subjects, while the 50 ms deviant tone evoked an observable
      MMN only in 32 of the subjects. The MMN peak amplitude for the 25 ms deviants was
      significantly larger than for the 50 ms deviants. There was no significant
      difference in the peak latencies (measured from stimulus offset). For the 25 ms
      deviant, the amplitude diminished with increasing age. The MMN curves for the 25
      ms deviant, measured on separate days in 14 subjects, looked very replicable. As
      a result of noise and filtering effect, the product-moment correlations were
      poor. The results indicate that the signal-to-noise ratio for the MMN to 25 ms
      deviants, obtained even in a 25 min recording session, is large enough for
      clinical use and individual diagnostics when undetectable (or very low amplitude)
      MMN is used as a sign of pathology. However, judged from the low correlation
      coefficients, despite the good replicability in visual evaluation, better methods
      for MMN quantification have to be used for clinical follow-up.

PMID- 9566629
TI  - Differential effects of normal aging on sources of standard N1, target N1 and
      target P300 auditory event-related brain potentials revealed by low resolution
      electromagnetic tomography (LORETA).
AB  - The P300 event-related potential (ERP) is considered to be closely related to
      cognitive processes. In normal aging, P300 scalp latencies increase, parietal
      P300 scalp amplitudes decrease and the scalp potential field shifts to a
      relatively more frontal distribution. Based on ERPs recorded in 172 normal
      healthy subjects aged between 20 and 88 years in an auditory oddball paradigm,
      the effects of age on the electrical activity in the brain corresponding to N1
      and P300 components were estimated by means of low resolution electromagnetic
      tomography (LORETA). This distributed approach directly computes a unique 3
      dimensional electrical source distribution by assuming that neighbouring neurons
      are simultaneously and synchronously active. N1 LORETA generators, located
      predominantly in both auditory cortices and also symmetrically in prefrontal
      areas, increased with advancing age for standards but remained stable for
      targets. P300 LORETA generators, located symmetrically in the prefrontal cortex,
      in the parieto-occipital junction and in the inferior parietal cortex
      (supramarginal gyrus) and medially in the superior parietal cortex, were
      differentially affected by age. While age did not affect parieto-occipital
      sources, superior parietal and right prefrontal sources decreased pronouncedly.
      Thus, in normal aging, P300 current density decreased in regions were a fronto
      parietal network for sustained attention was localized.

PMID- 9566630
TI  - Isoflurane plus nitrous oxide versus propofol for recording of motor evoked
      potentials after high frequency repetitive electrical stimulation.
AB  - The goal of this study was to test the influence of two widespread techniques of
      general anesthesia on motor evoked potentials (MEP) in response to transcranial
      and direct cortical high frequency repetitive electrical stimulation. Total
      intravenous anesthesia (TIVA) based on propofol and alfentanil was examined in 17
      patients (group A), and balanced anesthesia (BA), based on nitrous oxide,
      isoflurane and fentanyl, was studied in 13 patients (group B). Distinct motor
      responses were available in 15 of 17 patients (88%) of group A, and in one of 13
      patients (8%) of group B. Amplitudes increased significantly with increasing
      stimulus intensity and number of pulses under conditions of TIVA. At the same
      time, latencies decreased significantly with increasing stimulus intensity and
      decreasing interstimulus interval, but not with increasing number of pulses. It
      is hypothesized that propofol suppresses corticospinal I-waves at the cortical
      level, resulting in a conduction block at the level of the alpha-motoneuron, and
      that this effect may be overcome by high frequency repetitive stimulation. In
      contrast, nitrous oxide and isoflurane seem to have an additional suppressive
      effect on corticospinal D-waves, which may be overcome by higher stimulation
      intensity. In conclusion, transcranial high frequency repetitive stimulation and
      TIVA provide a feasible setting for intraoperative MEP monitoring, while higher
      doses of nitrous oxide and isoflurane are not compatible with recording of
      muscular activity elicited by the stimulation technique as described.

PMID- 9566631
TI  - High-frequency (600 Hz) SEP activities originating in the subcortical and
      cortical human somatosensory system.
AB  - Digitally high-pass filtered median nerve SEP show an oscillatory burst of low
      amplitude high-frequency (600 Hz) wavelets superimposed on the N20 component
      which itself is generated by excitatory postsynaptic potentials of area 3b
      pyramidal cells. Prior studies using magnetoencephalography (MEG) localized one
      wavelet generator close to the primary somatosensory hand cortex. Since MEG
      recordings are biased towards tangentially oriented and superficial generators, a
      dipole source analysis of 32-channel electric SEP recordings was employed here to
      test for the possibility of deep and/or radially oriented burst generators: in 10
      normal subjects low noise (16,000 averages) median nerve SEP were evaluated using
      dipole source analysis before and after applying a digital 475 Hz high-pass
      filter. Two main oscillatory 600 Hz burst sources were modeled; (i) a deep burst
      source close to the thalamus, most active in a time window between the brain-stem
      P14 and the cortical N20 sources, detectable in 7 of 10 subjects; most probably,
      this activity originates from deep axon segments of thalamocortical fibers; and
      (ii) a subsequent burst source timed around the N20 and located in the vicinity
      of the primary somatosensory hand cortex in all subjects, which was already known
      from MEG data. This superficial oscillatory source may be dominated by repetitive
      activity conducted in the terminal segments of the thalamocortical projection
      fibers initiated by the thalamic burst generator.

PMID- 9566632
TI  - Dissociation induced by voluntary movement between two different components of
      the centro-parietal P40 SEP to tibial nerve stimulation.
AB  - Whether the two earliest cortical somatosensory evoked potentials (SEPs) to
      tibial nerve stimulation (N37 and P40) are generated by the same dipolar source
      or, instead, originate from different neuronal populations is still a debated
      problem. We recorded the early scalp SEPs to tibial nerve stimulation in 10
      healthy subjects at rest and during voluntary movement of the stimulated foot. We
      found that the P40, which reached its highest amplitude on the vertex at rest,
      changed its topography during movement, since its amplitude was reduced much more
      in the central than in the parietal traces. These findings suggest that two
      different components contribute to the centro-parietal positivity at rest: (1)
      the P37 response, which is parietally distributed and is not modified by
      movement, and (2) the 'real' P40 SEP, which is focused on the vertex and is
      reduced in amplitude during voluntary movement. Since, also, the N37 response did
      not vary its amplitude under interference condition, it is possible that the N37
      and P37 potentials are generated by the same dipolar source. Other later
      components, namely P50 and N50 were significantly reduced in amplitude during
      foot movement. Lastly, the subcortical P30 far-field remained unchanged and this
      suggests that the phenomenon of amplitude reduction during movement (i.e. gating)
      occurs above the cervico-medullary junction.

PMID- 9566633
TI  - Multimodality evoked potentials as a prognostic tool in term asphyxiated
      newborns.
AB  - Hypoxic-ischemic (HI) events may cause permanent brain damage, and it is
      difficult to predict the long-term neurological outcome of survivors.
      Multimodality evoked potentials (MEPs), using flash visual (fVEPs), somatosensory
      (SEPs), and brain-stem auditory evoked potentials (BAEPs) may assess the cerebral
      function in term neonates. MEPs were recorded in 40 hypoxic-ischemic term or near
      term neonates during the first week of life in order to predict the neurological
      outcome. A 3 point grading system registered either mild, moderate, or severe
      abnormalities. At 24 months of corrected age, the infants were assessed with a
      blind protocol to determine neurological development. Grade 0 fVEPs and SEPs were
      associated with a normal neurological status with 100% (P < 0.001) of the
      infants. Abnormal SEPs or total grade (VEPs + SEPs) > I were not associated with
      normal outcomes (P < 0.0001). Normal BAEPs did not predict a normal outcome, but
      severely abnormal BAEPs did predict an abnormal outcome. A significant
      correlation was found between EP (VEPs + SEPs) grade (r = 0.9, P < 0.0001),
      Sarnat stage (r = 0.6, P < 0.001), and clinical outcome. This study confirmed
      that both fVEPs and SEPs are more accurate as prognostic indicators for term
      neonates. EPs (VEPs + SEPs) also are more accurate in predicting the ultimate
      neurological outcome compared with the Sarnat scoring.

PMID- 9566634
TI  - Chemosensory event-related potentials change with age.
AB  - The study examined age-related changes in the perception of olfactory and
      trigeminal chemical stimuli using chemosensory event-related potentials (CSERP).
      Three groups of healthy volunteers, each comprised of 8 men and 8 women, were
      tested (age ranges 15-34, 35-54, and 55-74 years). Subjects underwent extensive
      psychological testing focusing on impairments of memory and attention. In
      addition, odor identification and discrimination ability was evaluated, as well
      as detection threshold sensitivity for two odorants. Odor discrimination scores
      exhibited a significant age-related decrease. Significant age-related changes
      were also observed for CSERP N1P2 and P2 amplitudes, and for the N1 peak latency.
      The age-related decrease of CSERP amplitudes appeared to follow a different time
      course for responses to trigeminal and olfactory stimulants.

PMID- 9566635
TI  - The activated immune system in congestive heart failure--from dropsy to the
      cytokine paradigm.

PMID- 9566636
TI  - The activated immune system and the renin-angiotensin-aldosterone system in
      congestive heart failure.
AB  - OBJECTS: The aim of the study was to investigate a possible relationship between
      plasma renin activity, angiotensin II, serum levels of angiotensin-converting
      enzyme, aldosterone and markers of immune activation in congestive heart failure
      (CHF). PATIENTS AND METHODS: Fifty-three patients (50 male, three female, mean
      age 46 +/- 16 years) with congestive heart failure were studied. Twenty-eight
      patients had I or II NYHA class of CHF and 25 patients had III or IV NYHA class
      (NYHA class, mean +/- SD: 2.3 +/- 0.9). Serum neopterin concentration and
      hormones were measured by commercial radioimmunoassays. Serum soluble receptors
      of tumour necrosis factor and interleukin-2 were determined by ELISA. RESULTS:
      All analytes significantly correlated with NYHA classes (P < 0.05). There existed
      correlations between neopterin and angiotensin-converting enzyme or aldosterone
      (rs = 0.35 and rs = 0.36, P < 0.05). The soluble tumour necrosis factor receptor
      concentrations correlated with plasma renin activity (rs = 0.38, P < 0.05).
      CONCLUSION: The result of our study suggest that there exists some relationship
      between the renin-angiotensin-aldosterone system and immune activation in severe
      congestive heart failure, however, the associations found are rather weak.

PMID- 9566637
TI  - Perceived health modifies the effect of biomedical risk factors in the prediction
      of acute myocardial infarction. An incident case-control study from northern
      Sweden.
AB  - OBJECTIVES: To assess the importance of biomedical risk factors, social factors
      and self-reported health in the prediction of the first event of acute myocardial
      infarction (AMI) in an apparently healthy middle-aged population. DESIGN: An
      incident case-control study. SETTING: The study was nested within the
      Vasterbotten Intervention Program and the Northern Sweden MONICA cohorts.
      SUBJECTS: The study consists of 78 AMI cases with two randomly selected controls
      per case from the same study cohorts. RESULTS: Significant odds ratios were found
      for history of diabetes, daily smoking, cholesterol, body-mass index,
      hypertension, lower education and perceived ill health. In multivariate logistic
      regression smoking, hypertension and cholesterol of > or =7.8 mmol L(-1) remained
      significant. An interaction was observed between number of biomedical risk
      factors and perceived health. CONCLUSIONS: Smoking, hypertension and
      hypercholesterolaemia explain a major share of incident AMI events in a Swedish
      middle-aged population. The study further illustrates that perceived ill health
      negatively modifies the impact of these risk factors.

PMID- 9566638
TI  - Helicobacter pylori seropositivity is not associated with inflammatory
      parameters, lipid concentrations and degree of coronary artery disease.
AB  - OBJECTIVES: To determine the prevalence of chronic infection with Helicobacter
      pylori (HP) in patients with established coronary artery disease (CAD) and in
      healthy controls. Furthermore, to investigate whether HP infection is associated
      with inflammatory parameters, lipid concentrations and degree and progression of
      CAD. DESIGN: A case-control study combined with a prospective angiographic study.
      SETTING: Stockholm Metropolitan Area, Sweden. PATIENTS AND METHODS: A material
      consisting of 92 young men aged 40.9 +/- 3.2 (mean +/- SD) years, with previous
      myocardial infarction and documented coronary atherosclerosis, and 95 healthy sex
      matched controls, aged 43.2 +/- 3.0 (mean +/- SD) years, with similar socio
      economic status and ethnic background was analysed for the prevalence of HP
      seropositivity, plasma concentrations of the inflammatory parameters fibrinogen,
      tumour necrosis factor alpha and orosomucoid, and serum concentrations of lipids.
      The impact of HP seropositivity on degree and progression of CAD, as assessed by
      quantitative coronary angiography, was also determined. RESULTS: The study
      population of mainly Scandinavian origin had a low prevalence of HP
      seropositivity in comparison with previously published European populations. No
      significant increase in HP seropositivity was found in patients compared with
      controls (42.2 vs. 32.6%). Furthermore, HP infection was not associated with
      increased levels of inflammatory parameters, lipid concentrations or with degree
      of angiographically determined CAD at baseline, or progression of CAD and
      clinical events over 5 years. CONCLUSIONS: HP infection is not associated with
      inflammatory parameters and lipid concentrations and could not be confirmed as a
      risk factor for CAD.

PMID- 9566639
TI  - Increased biochemical markers of bone formation and resorption in primary
      hyperparathyroidism with special reference to patients with mild disease.
AB  - OBJECTIVES: To evaluate the impact on bone turnover of primary
      hyperparathyroidism (pHPT) with special reference to patients with mild pHPT,
      using biochemical markers of bone formation and resorption. DESIGN: A
      longitudinal study of patients with pHPT before and one year after surgical
      treatment. SETTING: The Departments of Internal Medicine and Surgery, Lund
      University Hospital. SUBJECTS: Forty consecutive patients with pHPT. Thirty of
      these patients had mild pHPT and are reported separately. Data on bone mineral
      was also compared to a reference population. INTERVENTION: All patients were
      operated upon and restudied one year later. MAIN OUTCOME MEASURES: Bone
      resorption and formation was studied by means of the serum concentrations of the
      telopeptide of the carboxyterminal region of type 1 collagen (ICTP) and of
      alkaline phosphatase (ALP), osteocalcin and the carboxyterminal propeptide of
      type 1 procollagen (PICP), respectively. Bone density was measured at the distal
      radius by single photon absorptiometry (SPA). RESULTS: Bone formation markers
      consistently decreased after parathyroid surgery: ALP from 3.51 +/- 0.23 to 2.94
      +/- 0.21 microkat L(-1) (P < 0.05), osteocalcin from 6.15 +/- 0.53 to 2.89 +/-
      0.23 microg L(-1) (P < 0.001) and PICP from 126.4 +/- 10.9 to 96.0 +/- 6.5 microg
      L(-1) (P < 0.001). In parallel, the ICTP concentration, reflecting bone
      resorption, decreased from 5.10 +/- 0.54 to 3.94 +/- 0.34 microg L(-1) (P <
      0.001). There was not any significant change in distal radius bone mineral 1 one
      year after surgery. In the subgroup of patients classified as mild pHPT, a
      significant decrease was noted for osteocalcin, PICP and for ICTP but not for
      ALP, without significant changes in variables reflecting distal radius bone
      mineral content. Glomerular filtration rate was inversely correlated to serum
      levels of intact PTH, ionized calcium, alkaline phosphatase, osteocalcin and ICTP
      and directly correlated to the 1.25-dihydroxy-vitamin D concentrations.
      CONCLUSIONS: pHPT is associated with substantial changes in circulating levels of
      biochemical markers of bone formation and resorption. These findings are also
      present in patients with mild pHPT. Renal function should be considered in the
      evaluation of the impact of pHPT on bone turnover.

PMID- 9566640
TI  - Bone mineral density in patients with Crohn's disease during long-term treatment
      with azathioprine.
AB  - OBJECTIVES: To ascertain whether patients with Crohn's disease treated with
      azathioprine maintained bone mineral mass better than patients treated with
      steroids alone. DESIGN: Retrospective study. SETTING: University Hospital of
      Malmo, Sweden. SUBJECTS: A total of 59 patients with ileocolonic, ileocaecal or
      colonic Crohn's disease. METHODS: Bone mass was assessed by dual photon X-ray
      absorptiometry at the level of L2-L4. RESULTS: Patients treated with a high
      lifetime dose of steroids (> 5 g prednisolone) had significantly (P = 0.011)
      lower Z-score of L2-L4 (-0.87 +/- 1.11; 11 SD) than steroid-treated patients, who
      had received a low dose of prednisolone (< 5 g) (0.08 +/- 1.16 SD). Azathioprine
      did not negatively influence the steroid effect on bone mineral density.
      CONCLUSIONS: Azathioprine does not seem to affect bone mineral density by itself.
      However, by being steroid-saving, it seems to conserve bone mineral mass in
      patients with Crohn's disease.

PMID- 9566641
TI  - QT interval and QT dispersion in systemic sclerosis (scleroderma).
AB  - OBJECTIVES: To measure QT interval and QT dispersion, and to evaluate possible
      relationships between these measurements, heart rate variability parameters, and
      early myocardial involvement in patients with systemic sclerosis (SSc). DESIGN:
      Prospective study. SETTING: Tertiary care centre, University 'La Sapienza', Rome,
      Italy. SUBJECTS: Thirty-eight patients with SSc (35 females and three males, mean
      age 47 +/- 11 years), 19 patients with the diffuse form of disease and 19 with
      the limited form, and 17 healthy controls (11 females and six males, mean age 43
      +/- 10 years) were studied. INTERVENTIONS: Both patients and control subjects
      underwent resting 12-lead electrocardiogram and 24-hour Holter monitoring.
      Moreover, resting myocardial scintigraphy with 99 m Tc-sestamibi was performed in
      all SSc patients. MAIN OUTCOME MEASURES: Bazett's formula was used to obtain rate
      corrected value of QT interval (QTc). QT and QTc dispersion were defined as the
      difference between maximum and minimum QT or QTc interval, respectively. Twenty
      four-hour heart rate variability was analysed both in the frequency and in the
      time domain. RESULTS: Twenty-three SSc patients (60.5%) had myocardial resting
      perfusion defects (group A) and 15 (39.5%) did not (group B). Maximum QTc
      interval, QT and QTc dispersion were significantly increased in SSc patients
      compared to the control subjects. No significant differences between group A and
      group B were observed for all QT measurements. Furthermore, maximum QTc interval,
      QT dispersion and QTc dispersion were significantly increased in group A patients
      compared to the control group. Total power, low-frequency, and high-frequency
      values were significantly lower in all SSc patients, whether in group A or group
      B, than in control subjects. On the other hand, low-frequency/high-frequency
      ratio was similar in all groups. Heart rate variability in time domain analysis
      showed no statistically significant differences between groups. CONCLUSIONS:
      Patients with SSc have increased QTc interval, QT dispersion, and QTc dispersion.
      The role of autonomic nervous system and myocardial involvement on ventricular
      repolarization in patients with SSc needs further investigation.

PMID- 9566642
TI  - Screening for coeliac disease in adult insulin-dependent diabetes mellitus.
AB  - OBJECTIVES: To study, by sequential screening for gliadin antibodies (GA) and
      endomysial antibodies (EMA), the prevalence and clinical characteristics of
      coeliac disease (CD) in adult IDDM patients. SUBJECTS AND MEASUREMENTS: A series
      comprising 1664 diabetes patients [848 with IDDM, 745 with non-insulin-dependent
      diabetes (NIDDM) and 71 with secondary diabetes] were screened for GA. IgA- or
      IgG-GA positive sera were analysed for EMA. RESULTS: IgA-GA were more frequent in
      all the diabetes subgroups (13.7% in IDDM,12.3% in NIDDM and 23.9% in secondary
      diabetes, P < 0.001 in all three cases) than among healthy blood donors (4.7%).
      Two patients with NIDDM had CD. Of the IDDM group (n = 848), 8 had previously
      diagnosed CD and 14 more (of whom 7 could be biopsied) were EMA positive. All had
      villous atrophy. The minimum prevalence of CD (including probable cases) in IDDM
      was 2.6% (22/848). Patients with previously known CD had more symptoms (P <
      0.001), more deficiency states (P < 0.001) and more autoimmune diseases (P <
      0.04) than those identified by screening. IDDM patients with a diabetes duration
      of 31-40 years were characterised by a higher prevalence of CD than patients with
      a duration of less than 30 years (6.7% vs. 1.7%; P < 0.02). CONCLUSIONS: Serial
      analysis of GA and EMA confirmed a high prevalence of CD in adult IDDM (2.6%).
      False-positive IgA-GA test results are frequent in patients with diabetes,
      irrespective of type. EMA analysis is the preferable screening tool for CD in
      diabetes.

PMID- 9566643
TI  - Muscle fibre composition and glycogen synthase activity in hypertension-prone
      men.
AB  - OBJECTIVES: To study muscle fibre characteristics and glycogen synthase activity
      in relation to peripheral glucose disposal in skeletal muscle in hypertension
      prone men. DESIGN: The hyperinsuliemic euglycemic clamp method was used to
      calculate insulin sensitivity index (M/I). Muscle biopsies were performed for the
      analysis of slow-twitch (ST) and fast twitch (FT, low insulin sensitivity and low
      capillarisation compared to ST fibres) muscle fibres, capillarisation (number of
      capillaries per fibre) and diffusional index (mean area per fibre divided by
      capillarisation) of muscle fibres, capillary density (capillaries mm(-2) muscle
      fibre) and glycogen synthase activity. SUBJECTS: Thirty-two young, healthy,
      normotensive men with a family history of hypertension (REL) were compared to 2 5
      age-matched men with no family history of hypertension (CON) and similar body
      mass index (BMI). RESULTS: REL had a lower M/I (P = 0.021), lower capillarisation
      (P = 0.04) and a tendency of a lower diffusional index of subgroup b of FT muscle
      fibres (P = 0.10) compared to CON. Glycogen synthase activity did not differ
      between the groups. CONCLUSIONS: Men with a family history of hypertension have
      less capillaries per FTb fibre and greater diffusion distance from the capillary
      to the muscle cell compared to controls, which may be a contributory factor to
      the lower insulin sensitivity in the former group. However, additional
      investigations are needed to study the causality in this association.

PMID- 9566644
TI  - Thyroid hormone treatment aiming at reduced, but not suppressed, serum thyroid
      stimulating hormone levels in nontoxic goitre: effects on bone metabolism amongst
      premenopausal women.
AB  - OBJECTIVES: To study the effects of six months' treatment with either T4 or T3,
      aiming at reduced but not totally suppressed serum TSH levels, as measured by a
      third generation TSH assay, on biochemical bone turnover parameters as well as
      bone mass in patients with nontoxic goitre. DESIGN: Prospective randomized study
      with a matched control group, not blinded. SETTING: Two University Hospital
      Clinics in Copenhagen. SUBJECTS AND INTERVENTION: Twenty-four consecutive
      premenopausal women with moderate sized nontoxic goitre. Fourteen patients
      randomized to T4 or T3 treatment for six months with monthly titration of the
      dose, aiming at TSH values between 0.005 and 0.2 mUL(-1). Ten controls. MAIN
      OUTCOME MEASURES: Serum parathyroid hormone (PTH), serum procollagen I C-terminal
      propeptide (PICP), serum alkaline phosphatase, serum osteocalcin, u-pyridinoline,
      u-deoxypyridinoline, u-hydroxyproline. Bone mass (BMD) at the lumbar spine and at
      both femoral necks. RESULTS: Serum TSH was generally kept within the desired
      interval. There was no difference in any marker of bone metabolism between the
      effects of T4 and T3. Consequently, these groups were combined in order to
      evaluate the effect of thyroid hormones on the bone and mineral metabolism.
      Thyroid hormone treatment resulted in increased levels of serum ionized calcium
      (Ca) (P=0.02), serum alkaline phosphatase (P=0.007), serum-PICP (P=0.003), serum
      osteocalcin (P=0.02) and urinary excretion of deoxypridinoline (P=0.03) compared
      to untreated controls. Bone mass did not change. CONCLUSION: Six months treatment
      with either T4 or T3 of premenopausal women with nontoxic goitre, aiming at
      reduced but not totally suppressed TSH values, resulted in biochemical signs of
      increased bone turnover, whereas bone mass remained unaltered. No differences
      were found between the effects of T4 or T3 treatment.

PMID- 9566645
TI  - Radiocontrast-induced natriuresis associated with increased urinary urodilatin
      excretion.
AB  - OBJECTIVE: Intravascular radiocontrast agents induce a pronounced diuresis. The
      aim of the present study was to investigate the (patho-)physiological mechanisms
      of the radiocontrast-induced diuresis. DESIGN: The fractional excretion of
      sodium, the urinary excretion of the renal natriuretic peptide urodilatin and the
      plasma concentration of atrial natriuretic peptide were measured in 42 unselected
      patients immediately before and after intravascular radiocontrast administration
      during coronary angiography. SETTING: Cardiac catheterization laboratory of a
      university hospital. RESULTS: After angiography both the plasma concentration of
      atrial natriuretic peptide (median post-pre difference: 3.9 pmol L(-1), quartiles
      -1.2; 7.0) and the urinary excretion of urodilatin (median post-pre difference:
      67.0 nmol urodilatin/mol creatinine, quartiles 39.7; 152.1) were increased. The
      urinary urodilatin excretion was correlated with an increase in the fractional
      excretion of sodium (median post-pre difference: 1.7%, quartiles 0.6; 3.1). There
      was no correlation between the serum concentration of atrial natriuretic peptide
      and urinary sodium excretion. For the radiocontrast-induced increase in both
      urodilatin and sodium excretion there was no indication for differences between
      patients without (31) and with (11) intravenous saline infusion. CONCLUSION: The
      radiocontrast-induced diuresis is a natriuresis which is associated with an
      increased urinary excretion of urodilatin. The association between natriuresis
      and urinary urodilatin excretion irrespective of baseline volume status
      corroborates the hypothesis that urodilatin contributes to the sodium excretion
      after radiocontrast administration in a paracrine manner. This finding has
      pathophysiological and potentially therapeutic implications in radiocontrast
      induced nephropathy.

PMID- 9566646
TI  - Effects of Simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid
      peroxidation in patients with combined hyperlipidaemia.
AB  - OBJECTIVES: Patients with combined hyperlipidemia are at increased risk for
      development of coronary heart disease. The purpose of this study was to evaluate
      the efficiency and the safety of treatment with Simvastatin and omega-3 fatty
      acids in patients with this lipid disorder. DESIGN: A double-blind placebo
      controlled, randomized study evaluating the effects of Simvastatin separately and
      in combination with omega-3 fatty acids in 41 healthy patients with defined
      hyperlipidemia. After a 16 weeks dietary run-in period the patients were treated
      in periods of 5 weeks. RESULTS: As expected Simvastatin (20 mg day[-1]) reduced
      serum total cholesterol, triacylglycerols, apolipoproteins B and E and increased
      HDL-cholesterol and apolipoprotein A1. Addition of omega-3 fatty acids (4 g day[
      1]) further decreased serum triacylglycerols (P = 0.007), total cholesterol (P =
      0.052) and apolipoprotein E (P = 0.035). No significant changes attributable to
      supplementation of polyunsaturated fatty acids on the content of lipid peroxides
      in plasma and in the various lipoprotein fractions were observed. CONCLUSIONS:
      The combined treatment of Simvastatin and omega-3 fatty acids seems to be an
      efficient and safe alternative for patients with combined hyperlipidemia.

PMID- 9566647
TI  - Recovery from Marie-Bamberger's syndrome and diabetes insipidus after removal of
      a lung adenocarcinoma with neuroendocrine features.
AB  - A 44-year-old woman with Marie-Bamberger's syndrome and diabetes insipidus had a
      lung tumour with mediastinal metastases, but no signs of metastases to the
      hypothalamus or pituitary gland. A week after removal of the tumour, the joint
      pain, polyuria and polydipsia disappeared. The tumour was diagnosed
      histopathologically as a moderately differentiated adenocarcinoma with focal
      neuroendocrine cell differentiation and dispersed cells reacting with antisera
      against neurone-specific enolase, S-100 protein, neuropeptide Y, follicle
      stimulating hormone, substance P, vasoactive polypeptide (VIP),
      adrenocorticotropic hormone and pancreatic polypeptide (PP) as well as to one of
      three tested antisera raised against antidiuretic hormone (ADH). It was suggested
      that Marie-Bamberger's syndrome might be caused by one of these immunoreactive
      substances or by a substance that shares an amino acid sequence with one of these
      neuroendocrine peptides. It was also suggested that the tumour might produce an
      ADH-like substance which might have an ADH-antagonist effect.

PMID- 9566648
TI  - Imported rickettsioses: think of murine typhus.
AB  - Murine typhus is a disease still prevalent in many parts of the world. Because
      the incidence in the US and Europe has declined rapidly, physicians in these
      continents have become unfamiliar with the clinical picture. Murine typhus is
      associated with significant morbidity and fatalities do occur, especially in the
      elderly and when late recognized. We present a patient with murine typhus that
      illustrates the wide variety of symptoms in this disease, which makes diagnosis
      difficult. However, if one keeps the possibility of murine typhus in mind, it is
      easily diagnosed and treated.

PMID- 9566649
TI  - Non-progressive congenital ataxia with or without cerebellar hypoplasia: a review
      of 34 subjects.
AB  - Information on the long-term development of larger series of children with non
      progressive congenital ataxia (NPCA) is scarce. We have updated a personal cohort
      of subjects previously diagnosed as having NPCA. Children with brain
      malformations, acquired neurological illness, or defined syndromes were excluded.
      From 58 subjects, 34 were available for review (including three pairs of
      siblings). All our subjects had delayed motor and speech development. Truncal
      ataxia persisted but became less significant. Two subjects developed spasticity
      and three a focal dystonia. Epilepsy was a feature in 10 of the subjects.
      Cognitive impairment was present in 22 of 34 subjects. MRI was normal in 15 of
      27. There were no obvious correlations between degree of motor delay, severity of
      ataxia, cognitive impairment, and neuroimaging. Although genetically and
      clinically not a homogeneous entity, NPCA is a helpful diagnostic label. Major
      problems arise in the majority of subjects related to cognitive impairment and
      less to neurological symptoms. Early individual prognosis is not possible from
      early developmental milestones, neurological signs, or neuroimaging.

PMID- 9566651
TI  - Delayed visual maturation: pupillary responses implicate subcortical and cortical
      visual systems.
AB  - Vision in very early infancy is probably subserved by subcortical pathways, with
      many cortical processes only fully emerging by 3 months of age. The improvement
      of vision in delayed visual maturation (DVM) occurs around this time, and this
      has given rise to the suggestion that the condition may have a subcortical basis
      that resolves with the appearance of cortical function. To explore further the
      role of cortical and subcortical visual systems in DVM we studied the visual
      development in identical twins, one of whom had type 1b DVM. Two non-invasive
      methods of investigating visual pathway function were employed: the acuity card
      procedure (a behavioural response) and luminance and grating pupillometry. While
      the former reflects both subcortical and cortical function and can be detected at
      birth, pupil responses to gratings reflect cortical activity alone and normally
      become measurable at 1 month of age. Development of both behavioural and
      pupillary responses was delayed in DVM, indicating that although the underlying
      defect is primarily subcortical, secondarily it delays the emergence of
      cortically mediated responses. The observed rapidity of improvement--over a very
      few days and within a narrow age range--suggests a discrete rather than a
      widespread structural abnormality, the improvement of which is closely linked to
      postmenstrual age.

PMID- 9566650
TI  - Children with blindness due to retinopathy of prematurity: a population-based
      study. Perinatal data, neurological and ophthalmological outcome.
AB  - A population-based group of 27 children with total blindness due to retinopathy
      of prematurity (ROP), born in Sweden from 1980 to 1990, was examined. They
      constituted all but two of the total of 29 children with total blindness due to
      ROP known to the national register of visually impaired children when reviewed
      from 1980 to 1 January 1995. All children had a gestational age of less than 31
      weeks and most had had a complicated perinatal period. The retinal disease was
      discovered late, most often after it had already progressed to bilateral retinal
      detachment. Repeated vitreoretinal surgery had been performed in most children,
      but postoperative visual function did not improve. Three-quarters of the group
      had major neurological impairment (mental retardation, cerebral palsy, or
      epilepsy) at age 4 to 14 years. There was an impression that extensive
      ophthalmological efforts delayed neurodevelopmental assessments and examinations
      as well as adequate habilitation.

PMID- 9566652
TI  - Infant nutrition and cognitive development in the first offspring of a national
      UK birth cohort.
AB  - Several studies show a modest beneficial effect of breastfeeding on cognitive
      development after controlling for sociodemographic confounders. It is still
      unclear, however, to what extent this is due to the nutritional advantage of
      breast milk or to environmental influences associated with breastfeeding. We
      compared verbal ability scores at age 8 years in 511 first-born offspring of the
      National Survey of Health and Development who were ever or never breastfed,
      adjusting for paternal occupation, maternal education, maternal cognitive
      performance, attendance at nursery school, and maternal age at birth of the
      participant. A positive association between breastfeeding and cognitive
      performance was found but this was no longer the case after adjusting for either
      paternal occupation, maternal education, or maternal cognitive performance in
      turn. In contrast, an association between breastfeeding and cognitive function
      was not found for mothers of these offspring. Breastfeeding was increasingly
      associated with a non-manual social class across the generations although it
      remains unclear how this might mediate the effect of breastfeeding on cognitive
      performance.

PMID- 9566653
TI  - Reflex excitability and isometric force production in cerebral palsy: the effect
      of serial casting.
AB  - During passive dorsiflexion, the angle of stretch-reflex onset was earlier in the
      dorsiflexion range for children with spastic cerebral palsy (CP) (N=10) compared
      with controls (P<0.001) at comparable velocities of stretch. Isometric plantar
      flexor force was lower in children with CP (P<0.0001) and a leftward shift in the
      length-tension curve reflected that peak forces were produced in greater plantar
      flexion in children with CP than in controls (P<0.0001). Seven children with CP
      underwent 3 weeks of serial casting resulting in increased dorsiflexion at
      postcasting and at 6 weeks follow-up (P<0.002). There was no associated loss in
      plantar-flexor strength (P>0.32), but increased reflex threshold (P<0.03) and a
      decline in restraint to imposed stretch (P<0.002) were evident. A rightward shift
      in the length-tension curve illustrated that peak tension was generated in
      dorsiflexion rather than plantar flexion following casting (P<0.001). The gains
      were still evident at follow-up although generally to a lesser extent.

PMID- 9566655
TI  - The impact of diagnostic labelling in population-based research into cerebral
      palsy.
AB  - This study explores and quantifies the impact on the estimation of prevalence
      rates and aetiological hypotheses of inclusion and exclusion of different
      diagnostic labels and types of cerebral palsy (CP). The study was based on data
      from a CP register which had been established in the English North East Thames
      Regional Health Authority (NETRHA). As a deliberate policy, no definition of CP
      was given to notifiers and no inclusion or exclusion criteria were specified.
      Clinical information, including known malformations, genetic disorders, and
      features that made the diagnosis doubtful, was requested. Rates and relative
      risks for different inclusion and exclusion criteria were calculated. The crude
      rate of CP as defined above was 1.6/1000 (95%CI 1.5, 1.7). Exclusion of all cases
      with a known or potentially causal association reduced this rate to 1.2/1000
      (95%CI 1.0, 1.3). Comparison with an intensively investigated sample from Germany
      and Sweden showed that more of the same causal associations (or diagnostic
      labels) were found, particularly where MRI studies had been carried out. Future
      comparative studies in CP will need to be very precise in specifying inclusions
      and exclusions and in estimating the effects they will have on monitoring trends
      over time and aetiological hypotheses.

PMID- 9566654
TI  - Effects of a movement and swimming program on vital capacity and water
      orientation skills of children with cerebral palsy.
AB  - Swimming and aquatic exercise are known for their effects on respiration in
      normal and asthmatic people. The purpose of the present study was to evaluate the
      effect of a 6-month movement and swimming program on the respiratory function and
      water orientation skills of children with cerebral palsy (CP). Forty-six
      kindergarten children aged 5 to 7 years were assigned either to a treatment or
      control group. The intervention program consisted of swimming sessions twice
      weekly and sessions of group physical activity in a gym once weekly, each session
      lasting 30 minutes, for a period of 6 months. Children in the control group were
      treated (30 minutes, 4 days per week) with Bobath physical therapy. The children
      in the treatment and control groups had comparable disability types, age, and
      anthropometric measurements. A 2 x 2 (group x test period) repeated measures
      ANOVA design confirmed a significant effect of interaction of time with group.
      The results also confirmed that children with CP have reduced lung function
      compared with normative data for children in the same age category. The treatment
      program improved baseline vital capacity results by 65%, while children in the
      control group improved by only 23%. The movement and swimming exercise program
      had a better effect than a physical therapy routine implemented in a previous
      study, consisting of respiratory exercise alone.

PMID- 9566656
TI  - Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment.
AB  - Nine girls with Rett syndrome (mean age, 10.1 years) were monitored 24 hours a
      day over a period of 10 weeks using wrist actigraphy. Baseline sleep-wake
      patterns were assessed for 1 week. Subsequently, patients underwent a 4-week
      melatonin treatment period in a double-blind, placebo-controlled, crossover
      protocol that employed a 1-week washout between treatment trials. Melatonin doses
      ranged from 2.5 to 7.5 mg, based upon individual body weight. Baseline sleep
      quality was poor compared with healthy children. At baseline the group
      demonstrated a low sleep efficiency (mean [+/- SE], 68.0+/-3.9%), long sleep
      onset latency (42.1+/-12.0 minutes), and a short and fragmented total sleep time
      (7.5+/-0.3 hours; 15+/-2 awakenings per night). Melatonin significantly decreased
      sleep-onset latency to (mean +/- SE) 19.1+/-5.3 minutes (P<0.05) during the first
      3 weeks of treatment. While the variability of individual responsiveness was
      high, melatonin appeared to improve total sleep time and sleep efficiency in the
      patients with the worse baseline sleep quality. Finally, a 4-week administration
      of melatonin appears to be a safe treatment as no adverse side effects were
      detected, yet long-term effects of chronic melatonin use in pediatric patients
      are unknown at this time.

PMID- 9566657
TI  - Bladder control a consequence of maturation: evidence after renal
      transplantation.
AB  - This report contains case studies on three children with early end-stage renal
      failure due to renal malformation or nephrotic syndrome, but without bladder
      involvement. All patients became anuric in the second year of life, before having
      obtained bladder control. They underwent successful cadaveric renal
      transplantation, having been anuric for almost 2 to 4 years. When the bladder
      catheter was removed 5 days after transplantation, all three children asked for
      the urine potty without ever having been prompted. Three weeks after
      transplantation, all three children achieved complete bladder control during the
      day, and two of them also at night. These observations add further evidence to
      the notion that the development of bladder control is a consequence of maturation
      and not of training.

PMID- 9566658
TI  - Acquired spinal cord lesion associated with os odontoideum causing deterioration
      in dystonic cerebral palsy: case report and review of the literature.
AB  - A boy with a dystonic quadriparesis presented with acquired paralysis,
      spasticity, and a feeding disorder. Spinal MRI revealed a cervical cord lesion
      and os odontoideum. Excessive movement of the neck, leading to failure of
      ossification of the dens and then to cervical cord trauma was the likely
      mechanism. The poor outcome of this subject is described, emphasising the need to
      pay careful attention to neurological changes in children with extrapyramidal
      cerebral palsy, who may be at particular risk of cord pathology. The management
      issues are discussed.

PMID- 9566659
TI  - Autoimmune and genetic disorders at the neuromuscular junction. The 1997 Ronnie
      Mac Keith lecture.

PMID- 9566660
TI  - Preeclampsia and cerebral palsy: are they related?

PMID- 9566661
TI  - The relevance of arthritis research in non-human primates.

PMID- 9566662
TI  - Standards of care for arthritis: pointing the way forward.

PMID- 9566663
TI  - Nitric oxide and inflammatory joint diseases.
AB  - Nitric oxide (NO) is synthesized from L-arginine by the NO synthases. At present,
      mainly three NO synthase isoenzyme groups are differentiated: two constitutive NO
      synthases, responsible for homeostatic cardiovascular and neuronal functions of
      NO, and an inducible NO synthase. After induction by certain cytokines or
      endotoxin, this latter isoform produces large quantities of NO with cyto- and
      bacteriotoxic effects. High amounts of NO, synthesized systemically and intra
      articularly, play an important role in inflammatory joint diseases, as shown in
      animal models of arthritis and in patients with rheumatoid arthritis or
      spondyloarthropathies. In experimental arthritis, administration of NO synthase
      inhibitors profoundly reduced disease activity. In humans, beneficial effects of
      NO synthesis inhibition are inferred from indirect evidence: glucocorticoids,
      inhibiting induction of the inducible NO synthase, reduce enhanced NO synthesis
      and disease activity. Thus, selective inhibition of the pathologically enhanced
      NO synthesis emerges as a new experimental therapeutic approach in the treatment
      of inflammatory joint diseases.

PMID- 9566664
TI  - The epidemiology of hyperuricaemia and gout in Taiwan aborigines.
AB  - To determine the prevalence of hyperuricaemia, gout and gout-related factors in
      Central Taiwan Atayal aborigines, 342 subjects over 18 yr old were interviewed
      and examined. A questionnaire was designed to screen for signs and symptoms of
      gout and gout-related risk factors. Serum uric acid, triglyceride and creatinine
      were measured in all subjects. The prevalence of hyperuricaemia was 41.4% and
      that of gout 11.7% in aborigines. The uric acid level was 7.9+/-1.7 mg/dl in
      males and 5.7+/-1.5 in females, and differed significantly under age 70 yr (P <
      0.001). Significantly increased triglyceride, creatinine and alcoholism was found
      in gouty patients compared with non-gouty patients. In 40 cases with gout, 54%
      had tophi and 35% of their first-degree relatives had gout. The high prevalence
      of hyperuricaemia and gout in Taiwan Atayal aborigines, a significant family
      predisposition, increased creatinine level and alcoholism suggest multiple
      factors affecting the hyperuricaemia.

PMID- 9566665
TI  - A longitudinal study of pulmonary involvement in primary Sjogren's syndrome:
      relationship between alveolitis and subsequent lung changes on high-resolution
      computed tomography.
AB  - Eighteen non-smoking women suffering from primary Sjogren's syndrome (pSS) with
      previously documented alveolitis were re-examined, clinically and by pulmonary
      function tests (PFT), bronchoalveolar lavage (BAL), chest X-ray and high
      resolution computed tomography (HRCT) after a 2 yr follow-up period. Longitudinal
      evaluation revealed unchanged PFT. The final BAL study showed a normal
      differential count in six of 14 patients with initial lymphocyte alveolitis, and
      a persistent alveolar lymphocytosis in the remaining eight patients, associated
      with an increased percentage of neutrophils in one of them. In four patients with
      initial mixed alveolitis, the BAL cell profile was unchanged 2 yr later. Five of
      18 patients (28%) had abnormal HRCT, represented by isolated septal/subpleural
      lines in three patients, ground-glass opacities with irregular pleural margins in
      one patient, and ground-glass opacities associated with septal/subpleural lines
      in another. All these patients had abnormal BAL results with an increased
      proportion of both neutrophils and lymphocytes. The presence of alveolar
      neutrophils was associated with a significantly (P=0.005) greater mean rate of
      reduction of carbon monoxide diffusing capacity (DLCO) -- more than four times
      the normal rate of loss of DLCO. Chest X-ray, repeated at the end of the 2 yr
      follow-up period, showed parenchymal abnormalities in only one patient who had
      evidence of fibrosis on HRCT. This study provides evidence that lung involvement
      is not an uncommon extraglandular manifestation of pSS and that a BAL
      neutrophilia may play an important role in the pathogenesis of pulmonary disease
      in this autoimmune disorder.

PMID- 9566666
TI  - Anti-neutrophil cytoplasmic autoantibodies in leprosy.
AB  - The objective was to evaluate the frequency of cytoplasmic and peripheral
      antineutrophil cytoplasmic antibodies (ANCA) in patients with leprosy, and to
      correlate the presence of ANCA with type and disease activity. Consecutive
      patients with leprosy were assessed clinically, and IgG ANCA were measured by
      indirect immunofluorescence. The presence of three of the following was used to
      assess disease activity: reactional state, fever, new cutaneous lesions,
      erythrocyte sedimentation rate and C-reactive protein. Sixty-four patients were
      studied and divided according to the Ridley-Jopling classification: of 38
      patients with lepromatous leprosy, eight (21%) had perinuclear (p) ANCA and two
      (6%) had cytoplasmic ANCA. ANCA titres ranged from 1:20 to 1:320. Of six
      borderline leprosy patients, one (16%) had p-ANCA. All 20 tuberculoid leprosy
      patients and 65 healthy control subjects had negative ANCA. There was no
      correlation between ANCA titres and disease activity in positive patients. ANCA,
      mainly those with a perinuclear pattern, may be present in leprosy, especially in
      the lepromatous pole. This disease should be added to the spectrum of diseases
      with ANCA positivity.

PMID- 9566667
TI  - Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis.
AB  - We tested the effects of an uncooked vegan diet, rich in lactobacilli, in
      rheumatoid patients randomized into diet and control groups. The intervention
      group experienced subjective relief of rheumatic symptoms during intervention. A
      return to an omnivorous diet aggravated symptoms. Half of the patients
      experienced adverse effects (nausea, diarrhoea) during the diet and stopped the
      experiment prematurely. Indicators of rheumatic disease activity did not differ
      statistically between groups. The positive subjective effect experienced by the
      patients was not discernible in the more objective measures of disease activity
      (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and
      pain on movement). However, a composite index showed a higher number of patients
      with 3-5 improved disease activity measures in the intervention group. Stepwise
      regression analysis associated a decrease in the disease activity (measured as
      change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll
      rich drinks, increase in fibre intake, and no need for gold, methotrexate or
      steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan
      diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid
      arthritis. Large amounts of living lactobacilli consumed daily may also have
      positive effects on objective measures of rheumatoid arthritis.

PMID- 9566668
TI  - Steroid pulse therapy for rheumatoid arthritis: effect on lymphocyte subsets and
      mononuclear cell adhesion.
AB  - Eighteen patients with clinically active rheumatoid arthritis, satisfying the ARA
      criteria, were admitted to hospital for i.v. methylprednisolone pulse therapy.
      Studies of circulating lymphocyte subsets 1 h before and 24 h after pulsing were
      carried out together with studies on their adhesion to endothelium-containing
      lamina propria of porcine gut at various time points. Additionally, circulating
      VCAM-1 was estimated pre- and post-pulse by ELISA. We observed a marked fall
      (59%) in mononuclear cell adhesion 24 h post-pulse therapy (P < 0.001).
      Accompanying this was a significant, though slight, fall in circulating
      mononuclear cells (P < 0.01), mainly involving T cells. However, the degree of
      reduction in cell adhesion did not appear to reflect change in any particular
      circulating subset, but was more likely due to changes in adhesion molecule
      expression of several subsets. No significant change in circulating VCAM-1 was
      observed. It would appear, therefore, that the early beneficial effect of steroid
      pulsing in rheumatoid arthritis coincides with a demonstrable reduction in cell
      adhesion to gut. This may have implications for the pathogenesis of this disease.

PMID- 9566669
TI  - An immunocytochemical study of the distribution of proline-4-hydroxylase in
      normal, osteoarthritic and rheumatoid arthritic synovium at both the light and
      electron microscopic level.
AB  - The monoclonal antibody 5B5 reacts with the beta subunit of proline-4
      hydroxylase, the enzyme which catalyses the formation of 4-hydroxyl proline in
      collagen and other proteins with collagen-like amino acid sequences. This study
      aims to assess the production and tissue distribution of this enzyme in normal
      and diseased synovia from patients with various joint diseases, on the basis that
      it is a putative marker of collagen-producing cells and, therefore, in this
      context, of fibroblasts. Sections from five normal, 10 osteoarthritic (OA) and 26
      rheumatoid arthritic (RA) synovia were labelled with a mouse monoclonal antibody
      to proline-4-hydroxylase. The enzyme was found to be expressed by a proportion of
      synovial intimal cells and by fibroblasts in the underlying connective tissue in
      normal, OA and RA synovia. Labelling was more pronounced in OA and RA cases. The
      intimal cells labelling positively showed type B synoviocyte morphology, which
      was confirmed by subsequent double immunolabelling with 5B5 and antibody against
      type IV collagen using immunocytochemistry and immunoelectron microscopy.

PMID- 9566671
TI  - Headache in systemic lupus erythematosus: a controlled study.
AB  - Intractable headaches, the so-called 'lupus headaches', have been long thought of
      as a common and characteristic manifestation of systemic lupus erythematosus
      (SLE). Seventy-eight patients with SLE, including 10 patients with definite
      central nervous system (CNS) involvement, and 89 healthy individuals matched for
      age, sex and socioeconomic status, were studied by a specific questionnaire
      addressing the characteristics and type of headache. Clinical features of SLE,
      neurological manifestations and treatment, disease severity and autoantibody
      profiles were correlated to the presence of headache. One year prevalence of
      headache was similar between patients (32%) and otherwise healthy individuals
      (30%). No significant differences regarding frequency, family history of headache
      and need for analgesic medication were observed. Headache refractory to analgesic
      treatment, but responsive to corticosteroid regimen, was recorded in only one
      patient. Clinical and serological features of SLE, including Raynaud's phenomenon
      and the presence of anticardiolipin antibodies, were not significantly different
      between headache sufferers and non-sufferers. In the majority of patients
      reporting headache, anxiety and/or depression co-existed. Episodic tension
      headache was the most frequent type, while migraine was traced in a quarter of
      headache sufferers. Neither the presence nor the clinical type of headache was
      related to, or predictive of, the development of seizures or psychosis. These
      results indicate that headache is not specifically related to SLE expression or
      severity, and suggest that accepting the presence even of a severe headache as a
      neurological manifestation of SLE in the absence of seizures or overt psychosis
      may result in overestimation of the disease status.

PMID- 9566670
TI  - The deleterious effects of low-dose corticosteroids on bone density in patients
      with polymyalgia rheumatica.
AB  - The beneficial effects of corticosteroid therapy in the treatment of rheumatic
      diseases may be offset by the occurrence of corticosteroid-related osteoporosis.
      This problem may be overcome by using low-dose corticosteroids; however, the dose
      of corticosteroids that is both efficacious and skeletal sparing is uncertain.
      Therefore, the aim of this study was to determine whether low-dose prednisolone
      treatment results in bone loss and modifies bone turnover. Nineteen patients (12
      female, seven male) suffering from polymyalgia rheumatica received 10 mg or less
      daily, given in reducing dosage, with a range of 2.5-10 mg and an average of
      6.0+/-0.2 mg daily (+/-S.E.M.). Prior to the commencement of therapy and at
      regular intervals during treatment, bone mineral density (BMD) using dual X-ray
      absorptiometry and circulating biochemical and hormonal determinants of bone
      turnover were measured. The patients were followed for 14.4+/-1.6 months (range 6
      27). They were compared to 19 age-matched controls. Despite a mean exposure dose
      of 6 mg/day and disease remission, BMD decreased in the patients at the lumbar
      spine (2.6+/-0.8%, P < 0.01), femoral neck (2.9+/-1.5%, P=0.06), Ward's triangle
      (5.5+/-2.9%, P=0.06) and the trochanter (4.3+/-1.9%, P < 0.05). Total body bone
      mass decreased by 50+/-19 g in the first 6 months (P < 0.02), and by 39+/-30 g in
      the remaining 8 months of follow-up [not significant (NS)]. In the first 6
      months, BMD decreased at the lumbar spine (1.7+/-0.9%, P = 0.06). From 6 months
      to the end of follow-up, BMD decreased by 8.5+/-3.5% at Ward's triangle (P <
      0.05) and by 4.8+/-2.5% at the femoral neck (P=0.08). The fall in BMD correlated
      with the cumulative prednisolone dose at trabecular-rich regions (trunk r=-0.72,
      P < 0.001; ribs r=-0.53, P < 0.05). Bone resorption, assessed by urinary cross
      laps, was 54.7% higher than controls before treatment was started (P < 0.05) and
      decreased by 23.5+/-7.1% in the first month of treatment when the mean
      prednisolone dose was 9.1 mg/day, range 5-10 (P < 0.0001). Serum osteocalcin was
      not suppressed by disease before treatment, decreased by 27.4+/-5.1% during the
      first month of treatment (P < 0.001), remained suppressed while the daily dose of
      prednisolone was > 5 mg/day, but returned to baseline below this dose. Serum
      parathyroid hormone was 19.3% lower in the patients than controls at baseline
      (NS), and increased by 46.1% (P < 0.05) but was no higher than controls at any
      time. Muscle strength increased by 20-60% (P < 0.05 to < 0.01). Prophylaxis
      should be considered in patients receiving > or = 5 mg/day prednisolone daily as
      bone loss is 2- to 3-fold expected rates. Earlier trabecular bone loss may
      predispose to spine and rib fracture; later cortical bone loss may predispose to
      hip fractures. Doses of prednisolone of < 5 mg daily may be skeletal sparing, but
      may not be efficacious.

PMID- 9566672
TI  - Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2
      receptors (sIL-2R) in scleroderma skin.
AB  - In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM
      1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin,
      and to compare their levels to concentrations measured in plasma and clinical
      parameters, we examined suction blister fluid and plasma from 13 patients with
      systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were
      from the transition zone between normal skin and scleroderma, and uninvolved
      abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in
      both plasma and suction blister fluid from systemic sclerosis patients compared
      with healthy volunteers. ICAM-1 was localized to vessels and perivascular
      mononuclear infiltrates by immunohistochemical methods. IL-2R was expressed by
      CD3-positive cells. The elevated levels of sICAM-1 and sIL-2R in suction blister
      fluid point towards activation of endothelial cells and T cells in both the
      transition zone and uninvolved skin of systemic sclerosis patients.

PMID- 9566673
TI  - Chickenpox monoarthritis: demonstration of varicella-zoster virus in joint fluid
      by polymerase chain reaction.
AB  - A case of chickenpox monoarthritis is described. The presence of varicella zoster
      virus (VZV) within the joint was demonstrated by the detection of viral DNA in
      synovial fluid at a time when peripheral blood cells were negative. This strongly
      suggests a direct role of VZV in causing monoarthritis complicating chickenpox.
      The use of the polymerase chain reaction allows more rapid (2 days) confirmation
      of the diagnosis. Early enough diagnosis would raise the question of using
      acyclovir to shorten the duration of arthritis.

PMID- 9566674
TI  - Collagen-induced arthritis in rhesus monkeys: evaluation of markers for
      inflammation and joint degradation.
AB  - The objective of this study was to analyse parameters in rhesus monkey collagen
      induced arthritis (CIA) with which the inflammation and destruction of the joints
      can be described in quantitative terms. CIA was induced in genetically
      susceptible and resistant monkeys, which can be distinguished on the basis of the
      dominant resistance marker Mamu-A26. The disease course was monitored daily using
      a semiquantitative scoring system. Plasma samples were collected once or twice
      weekly and analysed for C-reactive protein (CRP). Urines were collected overnight
      once a week and analysed for excretion rates of the collagen cross-links
      hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The results show that
      periods of active CIA are characterized by substantial weight loss and increased
      plasma CRP levels, followed shortly thereafter by increased excretion rates of
      the collagen cross-links HP and LP. Remission of the disease can be recognized by
      a decline in plasma CRP levels and especially an increase in body weight. The
      highest CRP levels were found in the most severely arthritic monkeys, indicating
      a possible relationship of the absolute plasma CRP levels to the severity of
      inflammation. During periods of active arthritis, increased excretion rates of
      collagen cross-links HP and LP in the urine were found. In particular, the major
      collagen cross-link in articular cartilage, HP, showed a strong increase (9- to
      15-fold). The excretion rates of LP, which is considered as a bone-specific
      degradation marker, only increased 4- to 6-fold, thus indicating predominant
      destruction of cartilage and less of bone. In conclusion, the severity of CIA can
      be monitored in a quantitative manner using plasma CRP levels, urinary excretion
      rates of HP and LP, and body weights, superimposed on semiquantitative clinical
      scores. The parameters also facilitate a more objective assessment of the effect
      of anti-arthritic drugs in the model than with the clinical scores alone.

PMID- 9566676
TI  - Relapse of Wegener's granulomatosis in the first trimester of pregnancy: a case
      report.
AB  - The association of Wegener's granulomatosis and pregnancy is rare and poses
      unique therapeutic challenges, particularly when active disease presents in early
      pregnancy. We describe a 22-yr-old woman who recovered successfully from her
      initial episode of Wegener's granulomatosis with a standard course of treatment
      with prednisolone and cyclophosphamide. Two and a half years later, she presented
      with relapse during the first trimester of pregnancy (primigravida). Since the
      clinical features suggested mild disease, she was started on prednisolone at a
      dose of 1 mg/kg/day, to which she seemed to respond very well for 3 months.
      Unfortunately, she had a spontaneous abortion at 5 months of gestation while on
      25 mg/day of prednisolone. At this time, her disease flared further, with
      clinically manifest lung disease which was not part of her initial presentation.
      She was treated with another course of oral cyclophosphamide and prednisolone,
      and a remission was achieved in 4 months. There are no agreed guidelines on the
      treatment of Wegener's granulomatosis during pregnancy. In this report, the
      therapeutic issues are discussed against the background of the available
      literature.

PMID- 9566675
TI  - Distribution of T cells and signs of T-cell activation in the rheumatoid joint:
      implications for semiquantitative comparative histology.
AB  - A prerequisite for comparative histology of synovial tissue by means of biopsies
      is insight into the distribution of a marker under study. This investigation
      focuses on the variation in the presence of T cells and signs of T-cell
      activation within the rheumatoid joint. For this purpose, multiple slides from
      several pieces of synovial tissue from different parts of a joint were stained
      and scored for the expression of CD3, CD25, HLA-DR, Ki67 and interferon-gamma.
      The variation in scores for the presence of T cells and markers of activation was
      more pronounced in slides prepared from different pieces of tissue than in slides
      from one piece of tissue. Based on multiple analysis of variance, methods are
      suggested to establish a reliable overall score for the expression of a certain
      marker within a joint. Following validation, such methods may prove to be useful
      by allowing semiquantitative histology of synovial tissue for studies on
      arthritis.

PMID- 9566677
TI  - International letter: the awakening of Latin American rheumatology.

PMID- 9566679
TI  - Clinical and immune peculiarities of pseudotuberculous polyarthritis against a
      background of chronic opisthorchiasis.

PMID- 9566678
TI  - Grand rounds in rheumatology: acute rheumatic fever or post-streptococcal
      reactive arthritis: a clinical problem revisited.

PMID- 9566680
TI  - Successful child bearing during intravenous cyclophosphamide therapy in a patient
      with systemic lupus erythematosus.

PMID- 9566681
TI  - Fluoroquinolones as a cause of tendon disorders in patients with renal
      failure/renal transplants.

PMID- 9566682
TI  - Successful response to angioplasty in a patient with upper limb ischaemia
      secondary to giant cell arteritis.

PMID- 9566683
TI  - First-time manifestation of generalized Wegener's granulomatosis despite
      methotrexate.

PMID- 9566684
TI  - Symptomatic antiphospholipid syndrome induced by chlorpromazine.

PMID- 9566685
TI  - Jaccoud's arthropathy in acrodermatitis chronica atrophicans.

PMID- 9566687
TI  - Pneumocystis carinii investigation in patients with Wegener's granulomatosis.

PMID- 9566686
TI  - Effect of low-dose cyclosporin treatment on interstitial pneumonitis associated
      with Sjogren's syndrome.

PMID- 9566688
TI  - p53 point mutation enhanced by hepatic regeneration in aflatoxin B1-induced rat
      liver tumors and preneoplastic lesions.
AB  - Aflatoxin B1 (AFB1) is a well-known mutagen and carcinogen which induces human
      hepatocellular carcinoma (HCC). It has been found to be an important factor in
      inducing a high frequency of codon 249 mutation in the p53 gene. We characterized
      p53 mutations in specimens from preneoplastic lesions or tumors from the liver of
      rats induced by AFB1 with or without regeneration by partial hepatectomy
      treatment. PCR-SSCP and direct sequencing were used for screening and
      identification of p53 gene mutations in these samples. In rats treated with AFB1
      with or without liver regeneration, 29% (5/17) of rats with hepatoma or
      neoplastic lesion had p53 mutation. No p53 mutations were found in the tumor
      samples from the rats without liver regeneration. However, in samples from the
      rats with liver regeneration, 38% (5/13) of the rats with hepatoma or neoplastic
      lesion were found to have p53 mutations. In one of these samples, we also
      observed a transversion mutation G --> T on codon 247, compared to codon 249 in
      humans. These findings suggest that the process of hepatocarcinogenesis induced
      by AFB1 does not necessarily involve p53 mutation, but mutation of the p53 gene
      can be enhanced by liver regeneration and that there is a possibility of a high
      mutability of the third base of codon 247, even though there is a small
      probability of detecting such a mutation in rats due to its silent mutation.

PMID- 9566689
TI  - Helicobacter pylori and gastric cancer in Croatia.
AB  - The seroprevalence of Helicobacter pylori infection was studied in a population
      from two areas of Croatia with significantly different average gastric cancer
      (GC) cumulative incidence and mortality rates. In a random sample of 456 blood
      sera from both areas, which was tested with the ELISA Helicobacter pylori
      antibody test, 48.8% of people in the north and 53.3% in the south of the country
      were found to be infected. The difference between the two areas in the
      seroprevalence of the infection was not statistically significant, nor did their
      populations differ in age, sex, educational background, smoking habit or wine
      consumption. Our results do not point to any association between the prevalence
      of Helicobacter pylori infection and the level of cumulative incidence and GC
      mortality levels.

PMID- 9566691
TI  - Epstein-Barr virus infection and response to radiotherapy in squamous cell
      carcinoma of the oral cavity.
AB  - We have retrospectively investigated the presence of Epstein-Barr virus (EBV) DNA
      in 45 cases of squamous cell carcinomas (SCCs) of the oral cavity using
      polymerase chain reaction (PCR). We analyzed the association between EBV
      infection and the clinicopathological characteristics, tumor response to
      radiotherapy, or prognosis to determine the clinical significance of EBV. EBV DNA
      was detected in 29 cases (64.4%) of SCCs. No significant differences were
      observed between the presence or absence of EBV. Our results indicate that EBV
      infection is not related to tumor response to radiotherapy, or the prognosis of
      the patients.

PMID- 9566690
TI  - Increased susceptibility of the c-Myc overexpressing cell line, SNU-16, to TNF
      alpha.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived multifunctional
      cytokine that acts as a cytostatic or cytotoxic agent in many tumor cells.
      However, the molecular mechanisms by which tumor cells become sensitive to the
      cytotoxic action of TNF-alpha are not clear. In this study we demonstrated that
      the cytotoxicity of TNF-alpha markedly increased in c-Myc overexpressing tumor
      cells. The stomach cancer cell line, SNU-16, in which c-Myc expression is high
      due to gene amplification, showed programmed cell death detected by DNA
      fragmentation and morphological changes. An antisense c-myc S-oligonucleotide
      specifically inhibited the TNF-alpha-induced apoptosis of SNU-16 cells, provided
      that the oligonucleotide was added 4 h prior to TNF-alpha treatment. Western
      immunoblot analysis of p53 and Bax showed that in this cell line, TNF-alpha
      increased the level of these proteins in a time-dependent manner and that this
      effect lasted for 12 h. Taken together these data indicate that the deregulation
      of c-Myc plays an important role in sensitizing tumor cells to TNF-alpha.
      Furthermore, TNF-alpha-induced apoptosis in the SNU-16 cell line showed increased
      expression of p53 and Bax protein levels following TNF-alpha treatment.
      Therefore, we suggest that TNF-alpha-induced apoptosis, which is cytotoxic to
      tumor cells, is coupled with a p53 and Bax apoptotic pathway.

PMID- 9566692
TI  - Report of a hitherto unreported sequence present and expressed in a cancer cell
      line.
AB  - During the amplification of a 202 base pair (bp) fragment around the 61st codon
      of the N-ras gene, an extra band of about 150 bp in length was observed when
      genomic DNA from a human epidermoid carcinoma cell line was used as template.
      This fragment was cloned and sequenced. However, this sequence was not found in
      the databank. RT-PCR experiments indicated that the sequence is expressed in the
      cells about 8 h after serum induction. The relevant RNA hybridized to one strand
      of the sequence but not to the other.

PMID- 9566693
TI  - Circulating vascular endothelial growth factor (VEGF) is not a prognostic
      indicator in malignant melanoma.
AB  - Among angiogenic peptides, vascular endothelial growth factor (VEGF) is
      associated with growth and metastasis of solid tumours. In order to determine
      whether VEGF could be involved in the clinical course of malignant melanoma, we
      studied 96 patients with primary or metastatic melanoma and we reported the
      follow-up of nine cases who initially presented with a primary melanoma and
      further developed metastasis over a period of 12-25 months. Circulating VEGF
      levels quantified by enzyme-linked immunosorbent assay were found to be elevated
      in patients with primary or metastatic melanoma compared to a control group (P <
      0.001), but no significant difference occurred between primary and metastatic
      melanoma. The follow-up of patients who developed metastasis showed high initial
      VEGF levels (in five out nine cases) which remained increased with the course of
      the disease. It is conceivable that increased VEGF levels reflect an intense
      activation of the host immune system but the variations in the concentration of
      circulating VEGF were not considered as an indicator of disease evolution in
      malignant melanoma.

PMID- 9566694
TI  - Antitumor efficacy of the combination of photodynamic therapy and chemotherapy in
      murine tumors.
AB  - Photodynamic therapy (PDT) is based on the administration of tumor-localizing
      photosensitizers followed by light exposure of the tumor mass. The photocytotoxic
      effects are mainly caused by the generation of singlet oxygen. Recently, PDT has
      been proposed for use in combination with anticancer chemotherapy with a view to
      exploiting any additive antitumor effect. We investigated the effect of PDT with
      photoactivated aluminum disulfonated phthalocyanine (AlS2Pc) combined with the
      antiblastic drugs Adriamycin (ADR) and cisplatinum (CDDP) on murine tumors. Mice
      bearing L1210 leukemia and P388 lymphoma were treated with ADR or CDDP and
      subsequently treated with PDT. Low chemotherapy doses were ineffective, but the
      combination of antiblastic drugs + PDT had a significantly additive antitumor
      effect. In conclusion, with this combined therapy we were able to greatly reduce
      the effective doses of antiblastic drugs, thus lowering their toxic effects on
      normal host tissues.

PMID- 9566695
TI  - Cytotoxic action of 2-deoxy-D-glucose tetraacetate in tumoral pancreatic islet
      cells.
AB  - Tumoral insulin-producing cells of the RINm5F line were cultured for 8-96 h in
      the absence or presence of 2-deoxy-D-glucose (0.15-0.80 mM) or its tetraacetate
      ester (0.08-0.80 mM). Despite the fact that over a short incubation of 120 min
      the utilization of D-[5-3H]glucose and oxidation of D-[U-14C]glucose were not
      more markedly decreased by 2-deoxy-D-glucose tetraacetate than by the
      unesterified glucose analogue, the growth of the tumoral cells, as assessed by
      either the generation of formazan from 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide or direct cell counting, was more severely affected
      by the ester than by 2-deoxy-D-glucose. At a high concentration (0.80 mM), the
      ester even decreased the cell number below its initial value. No restoration of
      cell growth was observed when the cells were exposed for only 8 h to 2-deoxy-D
      glucose tetraacetate (0.80 mM) and then further cultured for 64 h in the absence
      of the ester. These findings indicate that such an ester acts as a powerful
      cytostatic and cytotoxic agent in this tumoral cell line.

PMID- 9566696
TI  - Melatonin's growth-inhibitory effect on hepatoma AH 130 in the rat.
AB  - We tested the effects of daily melatonin treatment on the growth of the ascites
      hepatoma in rats, determining survival time, cell number and cell cycle phases at
      various stages of tumor development. Melatonin inhibited cellular proliferation,
      doubled mean life-time and increased survival. Thymidine incorporation in
      hepatoma cells from treated rats decreased significantly without changes in the
      apoptotic index. Flow cytometric analysis showed that melatonin slowed cell cycle
      progression by increasing the number of cells in phase G0G1. Thus, similar to in
      vitro models, melatonin's oncostatic action in vivo appears to be directed to
      specific cell cycle mechanisms, which remain to be elucidated.

PMID- 9566697
TI  - Benzo[a]pyrene diol-epoxide-I-DNA and oxidative DNA adducts associated with
      gastric adenocarcinoma.
AB  - BPDE-I-DNA and oxidative DNA adducts (8-OHdG) were investigated in stomach
      tissues (tumor and tumor-adjacent) of patients (N = 211) with gastric
      adenocarcinoma and in normal stomach tissues (N = 113). In each stomach specimen,
      the levels of BPDE-I-DNA adducts were quantitatively measured by enzyme linked
      immunosorbent assay (ELISA) and oxidative DNA damage was measured by HPLC-ECD.
      Higher levels of total BPDE-I-DNA adduct were observed in tumor (4.20 +/- 0.59
      fmol/microg DNA) and tumor-adjacent (3.68 +/- 0.62 fmol/microg DNA) tissues than
      in normal stomach tissues (2.80 +/- 0.53 fmol/microg DNA) but were not
      significant. In males, BPDE-I-DNA adduct was significantly higher in tumor
      tissues (4.25 +/- 0.42 fmol/microg DNA) than in normal tissues (2.83 +/- 0.59
      fmol/microg DNA) (P < 0.05). In smokers, BPDE-I-DNA adduct was slightly higher in
      tumor tissues (4.92 +/- 0.82 fmol/microg DNA) than in tumor-adjacent tissues
      (3.99 +/- 0.92 fmol/microg DNA). Gastric cancer patients had significantly higher
      levels of 8-OHdG in their tumor-adjacent (7.54 +/- 0.43 residues/10(5) dG) and
      tumor tissues (6.29 +/- 0.39 residues/10(5) dG) than in normal tissues (2.86 +/-
      0.11 residues/10(5) dG) (P < 0.001). Smokers showed higher levels of 8-OHdG in
      both tumor (6.44 +/- 0.62 residues/10(5) dG) and tumor-adjacent (8.12 +/- 0.68
      residues/10(5) dG) tissues than in non-smokers (5.80 +/- 0.47 and 7.11 +/- 0.57
      residues/10(5) dG, respectively). 8-OHdG levels were significantly increased in
      positive tissues with Helicobacter pylori (H. pylori) infection compared with
      negative tissues (P < 0.01). Also, the frequency of H. pylori infection was
      higher in tumor-adjacent tissues (73%) than in tumor (42%) or normal tissues
      (44%). These results demonstrate that there are higher levels of 8-OHdG and BPDE
      I-DNA adducts in tumor and tumor-adjacent tissues than in normal tissues and that
      these higher levels might be related to gastric tumorigenesis, although
      benzo[a]pyrene could be a minor contributing component in the environment.

PMID- 9566699
TI  - The radioprotective potential of the Bowman-Birk protease inhibitor is
      independent of its secondary structure.
AB  - The Bowman-Birk protease inhibitor (BBI), a serine-protease inhibitor, has been
      reported to exert both anticarcinogenic and radioprotective activity. In this
      work we examined whether this effect is mediated through inhibition of serine
      proteases of the trypsin-chymotrypsin type. Using linearized forms of BBI,
      evidence will be provided that the secondary structure, obligatory for the
      protease inhibitory function, is not necessary for the radioprotective effect.
      Detailed analysis indicated that the radioprotective effect is correlated with
      the chymotrypsin-inhibitory region of the molecule. Using a synthetic nonapeptide
      lacking protease inhibitor activity, the radioprotective effect of the total BBI
      molecule could be mimicked, indicating that the radioprotective effect is
      independent of the protease inhibitor function.

PMID- 9566698
TI  - Flaxseed and its mammalian lignan precursor cause a lengthening or cessation of
      estrous cycling in rats.
AB  - Flaxseed and its mammalian lignan precursor secoisolariciresinol diglycoside
      (SDG) have been shown to be mammary cancer-protective in rats. Thus, the
      antiestrogenic effects of flaxseed and SDG were compared with tamoxifen, an
      antiestrogen, by monitoring rat estrous cycling. Four-week supplementation of a
      high-fat diet with flaxseed (2.5, 5, or 10%) or SDG (0.75, 1.5 or 3.0 mg/day)
      produced a dose-related cessation or lengthening (by 18-39%) of estrous cycles in
      up to 66% of rats. With tamoxifen (1 mg/kg body weight/day), 83% of the animals
      had irregular cycles or were in persistent diestrus. Flaxseed and SDG were
      antiestrogenic without gross tissue toxicity.

PMID- 9566700
TI  - Dimethylarsinic acid, a main metabolite of inorganic arsenics, has tumorigenicity
      and progression effects in the pulmonary tumors of A/J mice.
AB  - The pulmonary tumorigenicity of dimethylarsinic acid (DMAA), a main metabolite of
      inorganic arsenics, was examined in A/J mice fed with drinking water containing
      DMAA for 25 and 50 weeks. Mice fed with 400 ppm DMAA for 50 weeks produced more
      pulmonary tumors than untreated mice (mean number per animal 1.36 versus 0.50; P
      < 0.05). Histological examination revealed that the number of mice which bore
      adenocarcinomas or papillary adenomas correlated with the concentration of DMAA
      given (untreated versus 400 ppm; P = 0.002), suggesting that DMAA could promote
      tumorigenic processes. These results are consistent with the epidemiological
      studies on the pulmonary carcinogenesis of arsenics and suggest that DMAA alone
      can act as a carcinogen in mice.

PMID- 9566701
TI  - Genetic alterations are frequent in APC but rare in the TGF-beta type II receptor
      gene in cancer in adenomas of the colon.
AB  - Cancer in adenomas are thought to be an excellent model of colorectal
      carcinogenesis based on the adenoma-carcinoma sequence. We searched for
      alterations in the APC mutation cluster region, the whole coding regions of TGF
      beta type II receptor (RII) and beta-catenin exon 3 in 16 cases of cancer in
      adenomas of the colon. Overexpression of the p53 protein was also analyzed. Nine
      of the 16 cases showed APC mutations in both the adenoma and cancer regions. Loss
      of heterozygosity in APC was found in one cancer in adenoma that had no mutation.
      p53 overexpression was detected in one adenoma and 10 cancerous regions, most of
      which also exhibited APC alterations. Two cases showed a missense mutation at
      codon 191 or loss of heterozygosity in TGF-beta RII in both the adenoma and
      cancer. Our data support the hypothesis that alterations of APC and p53 are
      responsible for most of the adenoma-carcinoma pathway, rather than TGF-beta RII
      alterations.

PMID- 9566702
TI  - Uptake of suramin by human microvascular endothelial cells.
AB  - We have demonstrated for the first time that suramin is taken up by human dermal
      microvascular endothelial (HMEC-1) cells by an active process involving the
      caveolae system. The uptake of suramin was time-dependent and reduced by more
      than 90% when incubated in the presence of albumin or at 4 degrees C. Suramin
      uptake was also inhibited when incubated in the presence of filipin and
      digitonin, both potent cholesterol-binding agents, but not in the presence of
      probenecid. The [3H]suramin taken up by the HMEC-1 cells was located primarily
      within the nucleus, followed by the cytoplasmic fraction. The presence of suramin
      in these cellular compartments suggests that this drug may act through
      intracellular mechanisms.

PMID- 9566703
TI  - Inhibitory effect of selenomethionine on the growth of three selected human tumor
      cell lines.
AB  - Selenium supplementation has been shown for many years to work as an
      anticarcinogenic agent both in epidemiology and in in vitro studies. Selenium
      supplementation has recently been shown to decrease total cancer incidence.
      However, the mechanism of action of selenium as an anticarcinogenic agent has yet
      to be elucidated. Selenomethionine was the predominant form of selenium in the
      dietary supplement in the study by Clark et al. (Clark, L.C., Combs, G.F.,
      Turnbull, W.B., Slate, E.H., Chalker, D.K., Chow, J., Davis, L.S., Glover, R.A.,
      Graham, G.F., Gross, E.G., Krongrad, A., Lesher, J.L., Park, H.K., Sanders, B.B.,
      Smith, C.L., Taylor, J.R. and The Nutritional Prevention of Cancer Study Group
      (1996) Effects of selenium supplementation for cancer prevention in patients with
      carcinoma of the skin: a randomized controlled trial. J. Am. Med. Assoc., 276
      (24), 1957-1963) and therefore we evaluated the growth inhibitory effects of
      selenomethionine against human tumor cells. Selenomethionine was tested against
      each of three human tumor cell lines (MCF-7/S breast carcinoma, DU-145 prostate
      cancer cells and UACC-375 melanoma) and against normal human diploid fibroblasts.
      All cell lines demonstrated a dose-dependent manner of growth inhibition by
      selenomethionine. Selenomethionine inhibited the growth of all of the human tumor
      cell lines in the micromolar (microM) range (ranging from 45 to 130 microM) while
      growth inhibition of normal diploid fibroblasts required 1 mM selenomethionine,
      approximately 1000-fold higher than for the cancer cell lines. In short, normal
      diploid fibroblasts were less sensitive than the cancer cell lines to the growth
      inhibitory effects of selenomethionine. Furthermore, we show that
      selenomethionine administration to these cancer cell lines results in apoptotic
      cell death and aberrant mitoses. These results demonstrate the differential
      sensitivity of tumor cells and normal cells to selenomethionine.

PMID- 9566704
TI  - Sex differences in dehydroepiandrosterone-induced hepatocarcinogenesis in the
      rat.
AB  - Dehydroepiandrosterone (DHEA), a steroid secreted by the adrenal gland, is a
      peroxisome proliferator and a hepatocarcinogen. Previously, we have shown that 15
      week-old male rats given DHEA in AIN-76 diet without vitamin E developed liver
      tumors. In the present study, we have examined the carcinogenic effect of DHEA in
      5-6-week-old male rats and in intact and ovariectomized female rats. Rats were
      fed Purina chow containing DHEA at a concentration of 0.45% for 100 weeks and
      livers were evaluated for tumor incidence and multiplicity. In male rats the
      incidence of total tumors and hepatocellular carcinomas (HCC) was 94 and 81%,
      respectively, with 1.9 +/- 0.3 (mean +/- SD) tumors per liver. In intact and
      ovariectomized females the total tumor incidence was 46 and 60%, respectively.
      However, the incidence of HCC and the mean number of tumors were similar in both
      intact and ovariectomized groups. Phenotypically the neoplastic nodules and HCC
      in female rats were negative for gamma-glutamyltranspeptidase. The results of
      these studies further confirm that DHEA is a hepatocarcinogen in male and female
      rats. The possible reasons for the decreased incidence of liver tumors in females
      in relation to the peroxisome proliferative effect of DHEA is discussed.

PMID- 9566705
TI  - Peroxidation of membrane lipids and oxidative DNA damage by fumonisin B1 in
      isolated rat liver nuclei.
AB  - Fumonisin B1 (FB1), a contaminant of corn, has been reported to be a
      hepatocarcinogen in rats. In an attempt to understand its mechanisms of action, a
      model system of isolated rat liver nuclei was used to determine what effects, if
      any, FB1 might have on nuclear membrane lipids and DNA. The data suggested that
      FB1 induced lipid peroxidation concurrently with DNA strand breaks in this in
      vitro system. Iron and copper had no statistically significant stimulatory
      effects on these reactions. In addition, the active oxygen scavengers catalase,
      superoxide dismutase (SOD), mannitol and sodium azide had no significant
      inhibitory effects on the FB1-induced DNA strand breaks. However, a small but
      significant reduction in lipid peroxidation by catalase and mannitol was
      observed. These results suggested that hydroxyl radicals may be the initiators of
      the nuclear membrane lipid peroxidation, which results in production of peroxyl
      radicals. In turn, the peroxyl radicals may be responsible for the DNA strand
      breaks. An alternative explanation is that the hydroxyl radicals, produced close
      to the DNA-bound metal ions, may induce direct site-specific strand breaks, which
      are insensitive to the scavengers of active oxygen.

PMID- 9566706
TI  - Enhanced expression of the 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase gene in
      human breast tumor cells.
AB  - The expression of the 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo
      dGTPase) gene in human breast tumors was evaluated at the level of the single
      cell to better understand how breast tumor cells regulate expression in response
      to oxidative stress. Compared to normal breast ductal cells, the level of 8-oxo
      dGTPase expression in the breast tumor cells increased from non-detectable levels
      in normal breast to expression in 30-85% of the tumor cells in individual tumors.
      There was no significant association between 8-oxo-dGTPase expression and tumor
      grade and metastatic malignancy. The upregulation of 8-oxo-dGTPase was not
      directly linked to the expression of cyclins D1 and D3, estrogen receptor, p53,
      Ki-67 and c-erbB-2, which are genes involved in cell cycle regulation and tumor
      growth. The elevated expression of 8-oxo-dGTPase in human breast ductal carcinoma
      cells appears to be a general characteristic of breast tumors and may provide the
      tumor cell with a cellular defense mechanism to prevent the incorporation of 8
      hydroxy-deoxyguanosine during DNA replication.

PMID- 9566707
TI  - PACAP(6-38) inhibits the growth of prostate cancer cells.
AB  - The effects of pituitary adenylyl cyclase activating polypeptide (PACAP) analogs
      on prostate cancer cell lines was investigated. 125I-PACAP-27 bound with high
      affinity to PC-3 cells (Kd = 10 nM) to a single class of sites (Bmax =
      30000/cell). By RT-PCR, a major 305 bp band was observed using cDNA derived from
      PC-3, LNCaP or DU-145 cells. Specific 125I-PACAP binding was inhibited with high
      affinity by PACAP-27, PACAP-38 and PACAP(6-38) (IC50 values of 15, 10 and 300 nM,
      respectively) but not by PACAP(28-38). PACAP elevated cAMP and the increase
      caused by PACAP-27 was reversed by PACAP(6-38). PACAP transiently increased c-fos
      gene expression and the increase in c-fos mRNA was reversed by PACAP(6-38). PACAP
      27 stimulated colony formation in PC-3 cells, whereas PACAP(6-38) reduced colony
      number and size. In nude mice bearing PC-3 xenografts, PACAP(6-38) significantly
      slowed tumor growth. These data suggest that biologically active type 1 PACAP
      receptors are present on human prostate cancer cells and that prostate cancer
      cell growth is inhibited by PACAP(6-38).

PMID- 9566709
TI  - Establishment of two human small cell lung cancer cell lines: the evidence of
      accelerated production of parathyroid hormone-related protein with tumor
      progression.
AB  - Two small cell lung cancer (SCLC) cell lines have been established from malignant
      effusions obtained from an SCLC patient with hypercalcemia during a 3-month
      follow-up period. The two cell lines established were shown to transcribe the
      parathyroid hormone-related protein (PTHrP) gene and to constantly secrete fairly
      large amounts of PTHrP into the culture medium. The efficiency of PTHrP gene
      transcription and secretion was greater in the cell line established in the late
      stage (KOT-2) as compared with that obtained in the early stage (KOT-1).
      Immunohistochemical studies showed that these cells also coexpress neuroendocrine
      (NE) products such as chromogranin A and neuron-specific enolase (NSE).

PMID- 9566708
TI  - Epithelial cell proliferation in the digestive tract induced by space restriction
      and water-immersion stress.
AB  - The effects of space restriction and water-immersion stress on epithelial cell
      proliferation in the digestive tract, with special attention to the esophagus,
      stomach and duodenum, in 8-week-old SD male rats were examined. Histological
      assessment revealed spotted hemorrhagic lesions in the fundus of the glandular
      stomach, accompanied by statistically increased 5-bromo-2'-deoxyuridine (BrdU)
      labeling index in the fundic and pyloric regions. Furthermore, biochemical
      analysis demonstrated an increased activity of ornithine decarboxylase (ODC) and
      spermidine/spermine N1-acetyltransferase (SAT), known as key late-limiting
      enzymes of the polyamine pathway, in the gastric fundus. The stress may induce a
      remarkable increase in expression of c-fos, c-jun and c-myc mRNAs in both fundic
      and pyloric regions of the glandular stomach. There were no remarkable changes in
      the esophagus. These results indicate that space restriction and water-immersion
      stress induced cell proliferation in the glandular stomach through overexpression
      of proto-oncogenes and increased ODC and SAT activities that might be related to
      the promotion of gastric carcinogenesis.

PMID- 9566711
TI  - Restriction fragment length polymorphism of the L-myc oncogene in non-Hodgkin's
      lymphoma patients from India.
AB  - We examined 89 non-Hodgkin's lymphoma (NHL) patients of Indian origin for EcoRI
      restriction fragment length polymorphism (RFLP) of the L-myc gene with a view to
      testing the hypothesis that the presence of the L-myc S-allele predisposes
      towards NHL. We found no significant difference either in the distribution of the
      LL, LS and SS genotypes or in the allelic frequencies between the patient group
      and the control group with the frequencies of L-myc alleles, L (10.0 kb) and S
      (6.6 kb), being 0.56 and 0.44, respectively, in the patient group and 0.54 and
      0.46, respectively, in the control group. However, a higher proportion (70%) of
      the S-allele was observed in our control group of normal healthy volunteers.
      Thus, the presence of L-myc S-allele did not indicate increased susceptibility or
      predisposition to the malignancy.

PMID- 9566710
TI  - Enhancement by antisense oligonucleotides to NF-kappaB of the differentiation of
      HL-60 promyelocytic leukemia cells induced by vitamin D3.
AB  - We have demonstrated previously that a phosphorothioate antisense oligonucleotide
      to the p65 subunit of the inducible transcription factor NF-kappaB produced rapid
      changes in the expression of leukocyte integrin CD11b (Mo 1) and in the adhesion
      of dimethylsulfoxide (DMSO)-differentiated HL-60 cells stimulated by 12-O
      tetradecanoylphorbol 13-acetate. We have also shown that a variety of agents
      which inhibit NF-kappaB, including vitamin E and related antioxidants, curcumin
      and several non-steroidal anti-inflammatory agents, significantly enhanced the
      differentiation of HL-60 leukemia cells when combined with low levels of 1,25
      dihydroxyvitamin D3 (vitamin D3). To provide further evidence that interference
      with the activation of NF-kappaB affects the maturation of HL-60 leukemia cells
      by creating an environment conducive to terminal differentiation, we measured the
      effects of phosphorothioate antisense oligonucleotides to the various subunits of
      NF-kappaB on the differentiation of HL-60 cells produced by low levels of vitamin
      D3. When used alone these oligonucleotides had no significant effect on the
      differentiation of HL-60 cells. However, the antisense oligomer to the Rel A
      subunit of NF-kappaB markedly increased the extent of differentiation produced by
      low levels of vitamin D3. An enhancement of the differentiation of HL-60 cells
      induced by vitamin D3 was also obtained by several transcription factor decoys
      designed to mimic the consensus sequences of genes activated by Rel A. The
      findings provide additional support for the concept that inhibition of the
      activation of NF-kappaB may be involved in regulating the entry of promyelocytic
      leukemia cells into a differentiation pathway.

PMID- 9566712
TI  - Prevention of severe hepatic injury by interferon-alpha in chronic active
      hepatitis lacking HBeAg (mutant strain) in a patient with malignant lymphoma.
AB  - Multidrug chemotherapy with concomitant interferon (IFN)-alpha was performed in a
      patient with chronic hepatitis lacking the hepatitis Be antigen and malignant
      lymphoma (ML). Levels of trans-aminases and DNA polymerase (DNA-P) values
      increased after the fifth course of chemotherapy. Therapy with IFN-alpha for 9
      weeks induced a remission in liver disease and complete remission of ML was
      obtained with subsequent chemotherapy. It was possible to prevent severe liver
      damage by administering IFN immediately after the elevation of DNA-P. Early
      introduction of IFN may be effective in the prevention of fulminant hepatic
      failure from hepatitis from a precore mutant after chemotherapy.

PMID- 9566713
TI  - Photodynamic therapy of ovarian tumours and normal cells using 5,10,15,20-tetra
      (3-carboxymethoxyphenyl)-chlorin.
AB  - The photosensitizing ability of the second generation photosensitizer 5,10,15,20
      tetra-(3-carboxymethoxyphenyl)-chlorin (m-TCMPC), a derivative of m-THPC, was
      tested on both three-dimensional multicellular spheroids of varying sizes and on
      monolayer cultures. These experiments were carried out on two spheroid-forming
      cell lines, A2780 (a human ovarian adenocarcinoma) and CHO (Chinese hamster
      ovarian cells). For both cell lines, photodynamic therapy (sensitizer plus
      visible light) treatments were carried out. The chlorin m-TCMPC was shown to have
      considerable promise as a photosensitizing agent. Cell kill was achieved for all
      situations tested, i.e. monolayer, 100, 500 and 750 microm spheroids. In addition
      no significant dark toxicity was observed.

PMID- 9566714
TI  - Pituitary adenylate cyclase activating polypeptide (PACAP) in human ovarian
      cancers.
AB  - Synthesis of regulatory peptides has been described in a number of ovarian
      tumours. The recently isolated neuropeptide pituitary adenylate cyclase
      activating polypeptide (PACAP) is expressed transiently in steroidogenic cells of
      normal rat ovary. In order to evaluate if ovarian tumours also synthesize PACAP,
      we investigated the expression and processing of pro-PACAP in 11 serous
      cystadenocarcinomas, one non-differentiated carcinoma, one borderline malignant
      and four adenomas. Using sequence specific radioimmunoassays and gel
      chromatography, we found that all tumours expressed PACAP-38 immunoreactivity.
      Ovarian cancers contained higher (P < 0.03) concentrations (median 0.9 pmol/g,
      range 0.5-1.6 pmol/g, n = 13) than benign tumours (median 0.5 pmol/g, range 0.4
      0.6 pmol/g, n = 4). Chromatography showed that the tumours contained PACAP-38 and
      PACAP-31-38 suggesting a rather complete processing. By immunohistochemistry, few
      scattered PACAP positive cells in small clusters or as single cells were
      identified in the tumours.

PMID- 9566715
TI  - Similarities between TNF and exogenous oxidants on the cytotoxic response of c
      Myc-expressing fibroblasts in vitro.
AB  - Normal fibroblasts are resistant to the cytotoxic activity of tumor necrosis
      factor-alpha, but are rendered TNF-sensitive upon oncogenic expression of c-Myc.
      Free radical generation has been implicated in non-cytotoxic TNF-signaling but
      also as a mediator of TNF-induced cell death. In this study we used Rat1
      fibroblasts containing a conditionally active form of oncogenic c-Myc (MycER) to
      investigate single cell line TNF-induced free oxygen radical formation during the
      non-cytotoxic TNF-response (inactive c-Myc) and cytotoxic response (active c
      Myc). The generation of reactive oxygen species (ROS) was assayed using a
      fluorescent probe, dichlorodihydrofluorescein (DCFH-DA), and the following
      cellular injury by measuring the high energy nucleotide (ATP, ADP and AMP)
      depletion. We found that TNF treatment of Rat1 cells containing c-Myc in an
      inactive form did not induce a detectable level of ROS generation. In contrast,
      TNF treatment of Rat1 cells containing activated c-Myc caused fluorescence
      reaction indicative of ROS generation within 80 min after DCFH-DA exposure of the
      cells. The nucleotide depletion likely reflected the action of ROS, since the
      nucleotide depletion caused by TNF or oxidants such as menadione or H2O2 in cells
      with active c-Myc was partly inhibited by the anti-oxidant N-acetylcysteine.

PMID- 9566716
TI  - Screening of edible Japanese plants for nitric oxide generation inhibitory
      activities in RAW 264.7 cells.
AB  - A total of 48 (60 test samples) species of plants commonly eaten in Japan were
      randomly collected and their methanol extracts were tested for in vitro nitric
      oxide (NO) generation inhibitory activities in a murine macrophage cell line, RAW
      264.7, stimulated with both lipopolysaccharide (LPS, 100 ng/ml) and interferon
      gamma (IFN-gamma, 100 U/ml). Seventeen (28.3%) of the 48 extracts strongly
      inhibited NO generation at a concentration of 200 microg/ml by 70% or more with
      significant cell viability (>50%). The extracts from avocado, taro, red turnip,
      sereves, komatsuna, basil, mitsuba and Chinese mustard markedly inhibited iNOS
      activity. These results suggest that a wide variety of edible plants in Japan
      contain the secondary metabolites carrying cancer preventive activity through
      reduction of excess amounts of NO.

PMID- 9566717
TI  - Sonodynamically-induced cell damage with fluorinated anthracycline derivative,
      FAD104.
AB  - The ultrasonically-induced in vitro cell damaging effect of fluorine-containing
      anthracycline derivative (FAD104) was investigated. Sarcoma 180 cells suspended
      in air-saturated PBS were exposed to ultrasound for up to 60 s in the presence
      and absence of FAD104. The rate of inducing cell damage with ultrasound was
      doubled with 80 microM FAD104, while no cell damage was observed with FAD104
      alone. This enhancement was significantly inhibited by histidine, which may
      suggest a sonochemical mechanism.

PMID- 9566718
TI  - Agonist activity of antiestrogen-receptor complexes to regulate urokinase
      plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1)
      endogenous gene expression in breast cancer cells.
AB  - We have shown that 4-hydroxytamoxifen (4-OHT) has estrogen-like effects on
      induction of TGFalpha mRNA in estrogen receptor (ER)-negative MDA-MB-231 human
      breast cancer cells, transfected with either wildtype (S30 cells) or a codon
      351asp-->tyr mutant ER (BC-2 cells). The mutant receptor used to produce the
      stable transfectants was identified in a tamoxifen-stimulated human breast tumor.
      We have also demonstrated that raloxifene exhibits a gene-specific estrogen-like
      effect with mutant ER (BC-2 cells) but not with wildtype ER (S30 cells)
      (Levenson, A.S., Catherino, W.H. and Jordan, V.C. (1997) Estrogenic activity is
      increased for an antiestrogen by a natural mutation of the estrogen receptor. J.
      Steroid Biochem. Mol. Biol., 60, 261-268). We now describe the regulation of
      urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type 1
      (PAI-1) endogenous gene expression by estradiol (E2) and different antiestrogens
      in BC-2 cells. Northern blot analyses revealed that 4-OHT and raloxifene have
      concentration-dependent agonistic (E2-like) effects on the regulation of these
      genes. In contrast, the pure antiestrogen ICI 182780 alone had no effect but
      could block the action of E2, 4-OHT and raloxifene. The E2-like effects of non
      steroidal antiestrogens in this model system cannot be explained by the mutation
      in the ER alone because 4-OHT acts as an agonist with wildtype receptor as well.
      We propose that the clear cut biological expression of estrogen-like qualities
      with different antiestrogens will in the future serve as an important model to
      dissect the signal transduction pathway.

PMID- 9566719
TI  - CD44 exon v6 is not implicated in the progression and metastasis of endometrial
      cancer.
AB  - We examined the presence of mRNA for CD44v6 and assessed the association with
      clinicopathological features in 42 patients with endometrial cancer by RT-PCR and
      subsequent Southern blot hybridization with oligonucleotide probe specific for
      v6. The standard form of CD44 was expressed in all specimens and 20 out of 42
      endometrial cancers expressed an isoform containing exon v6 in combination with
      other variant exons. However, there was no correlation between the expression of
      CD44v6 and any clinicopathological factors. These findings suggested that the
      expression of CD44v6 is not implicated in the progression and metastasis of
      endometrial cancer.

PMID- 9566720
TI  - Isolation and characterization of [3H]fucose-labeled glycoproteins from the serum
      of normal rats and rats bearing Zajdela hepatoma.
AB  - Specific [3H]fucose-labeled glycoproteins were found in the serum of rats bearing
      Zajdela hepatoma, which possess different isoelectric points in comparison with
      serum glycoproteins from normal rats. The electrophoretic profile of the serum
      glycoproteins is significantly altered. There is approximately a 2.5 times
      increase of [3H]fucose incorporation into serum glycoproteins from rats with an
      ascitic form of hepatoma, compared with normal rats and to animals bearing a
      solid form of the tumor (which have a considerably greater survival). Serum
      fucoproteins identical for the two forms of hepatoma were isolated, as well as
      glycoproteins strongly specific for each of the forms.

PMID- 9566721
TI  - Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables?
AB  - Indole-3-carbinol (I3C) is one of several compounds in brassica vegetables that
      demonstrate anticarcinogenic effects in experimental animals. A review of Medline
      and CancerLit databases indicated that interest in I3C, as a cancer
      chemopreventive agent, has increased significantly in the past 5-10 years.
      Whereas most studies report inhibitory or protective effects of I3C in vivo, a
      few provide clear evidence for promotion or enhancement of carcinogenesis,
      depending upon the initiator, exposure protocol and species. In the absence of
      detailed information on the inhibitory and in particular, promotional mechanisms,
      it would seem advisable to proceed with caution before including I3C in extensive
      human clinical trials.

PMID- 9566722
TI  - Modulation of DNA repair by various inhibitors of DNA synthesis following 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced DNA damage.
AB  - The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) is present in tobacco smoke and is hepatocarcinogenic in rats. Its
      bioactivation in rat hepatocytes leads to methylation and pyridyloxobutylation of
      DNA. Rat hepatocytes were cultured in serum-free William medium E on collagen
      coated dishes. We demonstrated that some enzymes of the base and/or excision
      repair pathways were involved in repair of NNK-induced DNA damage, measured by
      [methyl-3H] thymidine incorporation. Unscheduled DNA synthesis (UDS) induced by N
      methyl-N-nitrosourea (MNU), NNK, N'-nitrosonornicotine (NNN) and 4
      (acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc) increased 2.9-, 2.8
      , 1.5- and 3.5-fold, respectively, suggesting that methylated and/or
      pyridyloxobutylated-DNA by these four nitroso compounds is repaired by the
      excision pathway. Moreover, levels of NNK-induced UDS were dose (1-3 mM) and time
      (1-18 h) dependent. Enzymes involved in the excision repair pathways were
      selectively inhibited. Inhibitors of DNA topoisomerase I (camptothecin) and
      topoisomerase II (etoposide, nalidixic acid) did not decrease the induction of
      UDS, suggesting that topoisomerases are not involved in the repair of NNK-induced
      damage. While aphidicolin and arabinocytidine (DNA polymerase alpha, delta,
      epsilon inhibitors) totally inhibited NNK- and NNKOAc-induced UDS,
      dideoxythymidine (DNA polymerase beta inhibitor) inhibited NNK- and NNKOAc
      induced UDS by 40 and 33%, respectively. We conclude that DNA polymerase alpha,
      delta or epsilon and to a lesser degree polymerase beta are involved in the
      repair of pyridyloxobutylated DNA. Previous studies showed that inhibition of
      poly(ADP-ribosyl) polymerase (PARP) by 3-aminobenzamide (3-ab) facilitated DNA
      ligation. Our results demonstrate that 3-ab increased NNK-induced UDS, but does
      not affect NNKOAc-induced UDS. These observations suggest that the ligation step
      is rate limiting in the repair of methylated DNA but not of pyridyloxobutylated
      DNA.

PMID- 9566723
TI  - DNA sequence selectivity of cisplatin analogues in intact human cells.
AB  - The sequence specificity of ten cisplatin analogues was examined in intact human
      cells. Six of these compounds have anti-tumour activity. The sequence selectivity
      was investigated using a Taq DNA polymerase/linear amplification assay on damaged
      DNA extracted from treated cells. Cisplatin and tetraplatin(IV) produced strong
      damage and DACH RR(II) and cis-[Pt(II)Cl,2(iPrNH2)2] weak DNA damage in intact
      HeLa cells. The sequence selectivity of tetraplatin(IV) in intact human cells was
      very similar to that of cisplatin and favored runs of consecutive purines,
      especially consecutive guanines. The compounds transplatin, carboplatin, cis
      [PtCl(NH3)2(C8H17.NH2)], cis-[PtCl2(iPentNH2)2], cis-[PtCl2(C6H11NH2)2, DACH
      SS(II) and CHIP(IV) did not significantly damage DNA in cells. It was concluded
      that the interactions of these cisplatin analogues with DNA in human cells were
      strongly influenced by their ability to damage purified DNA.

PMID- 9566724
TI  - Rapid and transient induction of CYP1A1 gene expression in human cells by the
      tryptophan photoproduct 6-formylindolo[3,2-b]carbazole.
AB  - Studies to assess the induction of CYP1A1 gene expression by tryptophan derived
      oxidation products which are suggested as endogenous ligands for the Ah receptor
      are described. For the two high affinity Ah receptor ligands produced from
      tryptophan, the chemical structure was recently identified as 6-formylindolo[3,2
      b]carbazole (FICZ) and 6,12-diformylindolo[3,2-b]carbazole (dFICZ), respectively.
      Therefore these two compounds show a close similarity to the indolecarbinol
      derived condensation product indolo[3,2-b]carbazole (ICZ). Incubation of cells
      from a human keratinocyte (HaCaT) cell line together with ICZ, FICZ, dFICZ and
      some structurally related indole compounds was performed. The compound with the
      highest affinity to the Ah receptor, FICZ, was found to be the most efficient
      inducer of CYP1A1 gene expression in short time incubation (0.5 h) experiments.
      With longer incubation times (24 h) ICZ was the most efficient inducer. The two
      most active compounds, FICZ and ICZ, caused increased mRNA levels already at a
      concentration of 100 pM. FICZ was also shown to increase CYP1A1 mRNA levels in
      fresh human peripheral blood cells at the same low concentration. FICZ and ICZ
      were furthermore compared with regard to their capacity to inhibit cDNA-expressed
      human CYP1A1 enzyme and FICZ was found to be the most potent inhibitor. The
      inhibition was, however, transient in character indicating that FICZ is also an
      exceptionally good substrate for the CYP1A1 enzyme. The results showing the
      potent and transient effect of these formylindolocarbazoles, thus emphasize their
      important properties as signal substances in the Ah receptor pathway. This makes
      the most potent compound, FICZ, a good candidate for the endogenous ligand of the
      Ah receptor necessary for normal development and for the basal expression of Ah
      receptor-dependent genes.

PMID- 9566726
TI  - Sensitive 32P-HPLC technique shows base sequence dependent differences in
      photolesion repair in human keratinocytes.
AB  - Understanding the basis for individual susceptibility to skin cancer requires an
      understanding of the factors contributing to tumorigenesis. One such factor is
      the ability of the cell to repair DNA lesions induced following insult to the
      genome. Currently, research in this field is hampered by the lack of a suitably
      sensitive and specific method for the detection of DNA lesions. Developed
      previously 32P-HPLC in vitro analysis is applied in this study to measure UVB
      induced dipyrimidine photolesions in human keratinocyte cultures. The high
      sensitivity of this method permitted the detection of individual cyclobutane
      pyrimidine dimers and 6-4 photoproducts in cells irradiated with UVB at doses
      below one minimal erythema dose. Using this technique one could detect
      approximately a 2-fold difference in a base sequence repair of photolesions. The
      rates of repair in the chromosomally unstable HaCaT keratinocyte cell line and in
      cultured primary human keratinocytes were compared. The presented data indicate
      the potential of the 32P-HPLC method for the study of DNA repair in cultured
      cells as well as for biomonitoring studies in humans.

PMID- 9566725
TI  - Apoptosis as a mechanism of 2-chloroethylethyl sulfide-induced cytotoxicity.
AB  - Apoptosis is a mode of active cell death. We have examined whether 2
      chloroethylethyl sulfide (CEES), a sulfur vesicating agent, triggers apoptosis as
      a cytotoxic mechanism. Incubation of thymocytes with CEES, resulted in an
      induction of apoptotic features of cell death. Treatment of cells with 100 microM
      CEES for 5 h increased DNA fragmentation to approximately 40% of control. The
      fragmentation of DNA was visualized by agarose gel electrophoresis. It showed
      ladder pattern of DNA fragmentation, which indicates internucleosomal cleavage of
      DNA. Further evidence of apoptosis was observed in morphological changes of
      nuclei by using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end labeling (TUNEL) method. The percentage of TUNEL positive cells was
      dependent upon CEES concentrations. CEES induced the classical morphological
      features of apoptosis in nucleus. These features were accompanied by condensation
      of chromatin, which arranged in sharply declined clumps and fragmentation of
      nucleus. To study requirement for synthesis of new protein in CEES-induced
      apoptosis, we studied the effect of cycloheximide for apoptotic activity. This
      protein synthesis inhibitor did not suppress the CEES-induced apoptotic activity.
      Taken together, these results suggest that CEES-induced apoptosis as a
      cytotoxicmechanism and this process occurs independent of synthesis of new
      protein.

PMID- 9566727
TI  - Comparison of immunoaffinity chromatography enrichment and nuclease P1 procedures
      for 32P-postlabelling analysis of PAH-DNA adducts.
AB  - 32P-postlabelling analysis for detecting DNA adducts formed by polycyclic
      aromatic compounds is one of the most widely used techniques for assessing
      genotoxicity associated with these compounds. In cases where the formation of
      adducts is extremely low, a crucial step in the analysis is an enrichment
      procedure for adducts prior to the radiolabelling step. The nuclease P1
      enhancement procedure is the most established and frequently used of these
      methods. An immunoaffinity procedure developed for class specific recognition for
      polycyclic aromatic hydrocarbon (PAH)-DNA adducts has therefore been compared
      with the nuclease P1 method for a range of DNA adducts formed by PAHs. The
      evaluation was carried out with skin DNA from mice treated topically with
      benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, 5-methylchrysene or chrysene. The
      immobilised antibody had the highest affinity for adducts structurally similar to
      the BPDE-I-deoxyguanosine adduct ([+/-]-N2-(7r,8t,9r-trihydroxy-7,8,9,10
      tetrahydrobenzo[a]pyrene-1 0t-yl)-2'-deoxyguanosine) against which the antibody
      had been raised. Of the PAH-modified DNAs evaluated, the maximum adduct recovery
      was obtained for DNA containing the BPDE I-deoxyguanosine adduct. With DMBA
      modified DNA, the profiles of adducts recovered from the column were similar when
      the column material was treated either with a digest of DMBA-modified DNA or with
      32P-labelled DMBA adducts. I-compounds (endogenous adducts in tissue DNA of
      unexposed animals), which had similar chromatographic properties to PAH-DNA
      adducts, were not enriched by the immunoaffinity procedure. Compared to the
      simple nuclease P1 enhancement procedure, the immunoaffinity methods were
      lengthier and more labour intensive. Advantages of the immunoaffinity procedure
      include: specificity, allowing the selective detection of a certain class of
      adducts: efficient adduct enrichment, providing a viable alternative to other
      enrichment procedures; adequate sensitivity for model studies and the potential
      to purify adducts for further characterisation. However, as a general screen for
      detecting the formation of DNA adducts, the nuclease P1 procedure was viewed as
      the initial method of choice since it was capable of detecting a wider range of
      PAH-DNA adducts.

PMID- 9566728
TI  - Cytochrome P450-dependent desaturation of lauric acid: isoform selectivity and
      mechanism of formation of 11-dodecenoic acid.
AB  - Cytochrome P450-catalyzed desaturation reactions have been reported infrequently
      in the literature. Previously, we documented the formation of the terminal
      olefinic metabolite of valproic acid by various members of the CYP2B and CYP4B
      sub-families. However, despite the extensive use of fatty acid substrates in drug
      metabolism studies, other examples of terminal desaturation at non-activated
      carbon centers are lacking. The goals of the present studies were to determine
      whether the archetypal P450 substrate, lauric acid (dodecanoic acid; DDA), also
      undergoes desaturation reactions, identify specific rabbit P450 isoforms which
      catalyze this reaction and examine its mechanism. A highly sensitive, capillary
      GC/MS assay was developed to separate and quantitate the trimethylsilyl
      derivatives of 11-ene-DDA, cis- and trans-10-ene-DDA and cis- and trans-9-ene
      DDA. Among all of these potential olefinic metabolites, only 11-ene-DDA was
      formed at a significant rate by rabbit liver microsomes. The formation of 11-ene
      DDA was NADPH-dependent, and was induced markedly by acetone pre-treatment, but
      not by phenobarbital, rifampin or Arochlor 1254. Studies with seven purified,
      reconstituted rabbit P450 isoforms showed that the most rapid rates of
      desaturation were obtained with CYP2E1, CYP4A5/7 and CYP4B1. Non-competitive,
      intermolecular isotope effect experiments, conducted with [12,12,12-2H3]DDA and
      [11,11-2H2]DDA, demonstrated further that CYP4B1-mediated terminal desaturation
      of DDA is initiated by removal of a hydrogen atom from the omega-1 rather than
      the omega position.

PMID- 9566730
TI  - Biology and function of the reversible sulfation pathway catalysed by human
      sulfotransferases and sulfatases.
AB  - Sulfation and sulfate conjugate hydrolysis play an important role in metabolism,
      and are catalysed by members of the sulfotransferase and sulfatase enzyme super
      families. In general, sulfation is a deactivating, detoxication pathway, but for
      some chemicals the sulfate conjugates are much more reactive than the parent
      compound. The range of compounds which are sulfated is enormous, yet we still
      understand relatively little of the function of this pathway. This review
      summarises current knowledge of the sulfation system and the enzymes involved,
      and illustrates how heterologous expression of sulfotransferases (SULTs) and
      sulfatases is aiding our appreciation of the properties of these important
      proteins. The role of sulfation in the bioactivation of procarcinogens and
      promutagens is discussed, and new data on the inhibition of the
      sulfotransferase(s) involved by common dietary components such as tea and coffee
      are presented. The genetic and environmental factors which are known to influence
      the activity and expression of human SULTs and sulfatases are also reviewed.

PMID- 9566729
TI  - Paracetamol increases sensitivity to ultraviolet (UV) irradiation, delays repair
      of the UNG-gene and recovery of RNA synthesis in HaCaT cells.
AB  - We have studied the effect of low levels of paracetamol (0.3 and 1.0 mM) on gene
      specific DNA repair, recovery of total RNA synthesis and cytotoxicity after
      exposure of human keratinocyte cells (HaCaT) to ultraviolet (UV) irradiation.
      Repair of cyclobutane pyrimidine dimers (CPDs) was measured in the
      transcriptionally active uracil-DNA glycosylase (UNG) and c-MYC loci. Repair of
      both strands in the UNG gene was consistently lower in the presence of
      paracetamol, but this reduction reached significance only at 8 h after
      irradiation and no dose-response was observed. For the c-MYC gene, we found no
      significant effect of paracetamol on the repair of CPDs, possibly because UV
      irradiation is known to induce transcription of the c-MYC gene and enhanced
      transcription coupled repair might counteract a negative effect of paracetamol on
      global genome repair. A dose-dependent delay in the recovery of total RNA
      synthesis after UV exposure was observed in the presence of paracetamol, which
      also caused a 20% increase in UV-induced cytotoxicity after 24 h. Paracetamol had
      no significant effect on either RNA synthesis or cell survival in the absence of
      UV after 24 h, but reduced cell survival by approximately 10% (at 0.3 mM) and
      50%, (at 1.0 mM) after 96 h exposure. Our results demonstrate that paracetamol
      may inhibit gene-specific repair of CPDs by affecting global genome repair and
      that different genes may be differentially affected.

PMID- 9566731
TI  - Cloning of the human phenol sulfotransferase gene family: three genes implicated
      in the metabolism of catecholamines, thyroid hormones and drugs.
AB  - Phenol sulfotransferases (PST) catalyze the sulfonation of catecholamines,
      thyroid hormones and phenolic drugs. At least two major forms of human PST enzyme
      have been characterized biochemically from liver, platelets and other tissues,
      the phenol-preferring PST (P-PST) and the monoamine neurotransmitter-preferring
      PST (M-PST). Molecular cloning efforts worldwide over the past 7 years have
      resulted in the identification of numerous PST cDNA isolates representing alleles
      of three human PST gene loci termed as STP1, STP2 and STM. All three genes have
      been mapped precisely to a small region on human chromosome 16p12.1-p11.2
      (homologous to mouse chromosome 7), using somatic cell hybrids and cosmid clones.
      The two most closely related genes, STP1 and STP2, encoding P-PST isozymes have
      been mapped to a single cosmid clone and are, therefore, in close proximity to
      one another. STP1 and STP2 are approximately 96% identical at the amino acid
      sequence level, whereas, the STM gene (encoding M-PST) exhibits a lower level of
      identity (approximately 93-90.5%) relative to STP1 and STP2. STM is located at a
      distance of ca. 100 Kb from the STP1 and STP2 doublet. One may speculate that the
      three genes arose by gene duplication and/or gene conversion in humans. Genomic
      clones have been sequenced to determine the genomic organization for each of the
      three highly-related genes. All contain seven coding exons, with conserved intron
      exon boundaries. Sequencing of individual cDNA isolates of STP1 and STM from
      various tissues has revealed significant heterogeneity in the 5' nontranslated
      region, likely due to alternative splicing and/or tissue-specific promoter
      utilization. DNA polymorphisms have been detected in these genes in the human
      population and may be useful for molecular genetic studies of the metabolism of
      endogenous and xenobiotic phenolic molecules. Recent advances in the molecular
      biology of the human PST gene family are summarized.

PMID- 9566732
TI  - Novel sulfotransferases cloned by RT-PCR: real proteins or PCR artifacts?
AB  - During studies designed to subclone human phenol sulfotransferase (STP and STM)
      sequences for use in heterologous E. coli-based expression systems, we designed
      two oligonucleotide primers that would allow for the simultaneous PCR
      amplification of expression cassettes containing the coding regions of the STP1,
      STP2 and STM cDNAs. Following total RNA isolation from human liver, reverse
      transcription of cDNA, PCR amplification under standard conditions, plasmid
      subcloning and restriction analysis to select for suitable ST recombinants, we
      recovered plasmids containing inserts corresponding to STP1, STP2 and STM.
      However, ten additional, closely related but apparently novel ST sequences were
      also isolated. Alignments of the three known ST sequences (and one published
      allelic variant) with these new clones revealed that each one appears to be a PCR
      generated modular chimera possessing a combination of DNA segments derived from
      STP1, STP2 and STM. This observation should serve as an alert to the potential
      pitfalls of using PCR techniques for the cloning of highly related genes and
      their cDNA products, especially when PCR primer design allows for the
      amplification of multiple products in a single reaction.

PMID- 9566733
TI  - Sulfation of minoxidil by multiple human cytosolic sulfotransferases.
AB  - Minoxidil is an antihypertensive agent and hair growth promoter that is
      metabolized by sulfation to the active compound, minoxidil sulfate. Thermostable
      phenol sulfotransferase (TS PST or P-PST) was initially thought to catalyze the
      reaction, and the enzyme was designated minoxidil sulfotransferase (MNX-ST).
      Information about human ST activities toward minoxidil would be useful in
      developing the capacity to predict individual responses to minoxidil based on
      tissue levels of STs. Therefore, human STs were studied from platelet
      homogenates, partially purified platelets, scalp skin high speed supernatants and
      COS-1 cell cDNA expressed preparations using a radiochemical enzymatic assay with
      minoxidil as the substrate. Studies showed the presence of TS PST, TL
      (thermolabile) PST and MNX-ST activities in human scalp skin. Biochemical
      properties and correlation studies suggested that in addition to TS PST, the TL
      PST activity, another ST activity or both were involved in the reaction.
      Partially purified human platelet TL PST tested with minoxidil and dopamine
      showed identical thermal stabilities and similar responses to the inhibitors 2,6
      dichloro-4-nitrophenol (DCNP) and NaCl. To characterize the activity of TL PST
      toward minoxidil, several biochemical properties of the enzyme expressed from a
      human liver cDNA clone were investigated. When assayed with minoxidil and
      dopamine, thermal stabilities of the expressed enzyme were identical and IC50
      values for the inhibitors DCNP and NaCl were similar. It was also demonstrated
      that cDNA encoded human liver dehydroepiandrosterone sulfotransferase and
      estrogen sulfotransferase contributed to the sulfation of minoxidil. The results
      confirm that at least four human STs contribute to minoxidil sulfation. MNX-ST
      activity represents a combination of ST activities. The data indicate that
      multiple ST activities should be taken into account in attempts to predict the
      regulation of minoxidil sulfation and individual responses to minoxidil.

PMID- 9566734
TI  - On the nature of rat hepatic and mouse olfactory sulfotransferases.
AB  - Rat hydroxysteroid sulfotransferase (HS-SULT) cDNAs, ST-40 and ST-20 are 90%
      identical in amino acid sequences and show different substrate specificities
      toward dehydroepiandrosterone (DHEA), androsterone (AD) and cortisol (CS). ST-40
      enzyme is active toward the three substrates, whereas ST-20 enzyme is
      preferentially active for CS. First we prepared mutants of well conserved
      histidine, lysine and asparagine by site-directed mutagenesis. Secondly we
      constructed 20 chimeric HS-SULTs by reciprocal exchange of five protein domains
      between ST-20 and ST-40 enzymes. The studies on the expressed mutant and chimeric
      enzymes indicate the importance of the C-terminal region for the substrate
      specificity and the involvement of multiple regions for the enzyme activities.
      Next we determined the genetic loci of ST-40 and ST-20 by fluorescence in situ
      hybridization. Biotinylated ST-20 and ST-40 probes gave a pair of fluorescent
      spots on the same region of rat chromosome 1 and the loci of these genes were
      localized to the same chromosomal region of 1q21.3 --> q22.1. Finally we studied
      mouse olfactory phenol SULT (P-SULT). It was immunolocalized in the cytoplasm of
      mouse olfactory sustentacular cells and mouse nasal cytosols show high SULT
      activities toward phenolic aromatic odorants. We subsequently isolated a mouse P
      SULT cDNA from mouse olfactory cDNA library. It encodes 304 amino acid
      polypeptide and is 94% identical with rat ST1C1 in amino acid sequences.

PMID- 9566735
TI  - Studies on an affinity label for the sulfuryl acceptor binding site in an aryl
      sulfotransferase.
AB  - Active site-directed affinity labeling was utilized to elucidate peptide
      sequences at the binding site for sulfuryl acceptors in rat hepatic aryl
      sulfotransferase (AST) IV (also known as tyrosine-ester sulfotransferase, EC
      2.8.2.9). The affinity labeling reagent, N-bromoacetyl-4-hydroxyphenylamine, was
      designed on the basis of substrate specificity studies with para-substituted
      phenols, utilization of a bromoacetamido group for reactivity with active site
      amino acid residues and its similarity to acetaminophen, a known substrate for
      aryl (phenol) sulfotransferases. AST IV utilized N-bromoacetyl-4
      hydroxyphenylamine as a substrate with kinetic constants that compared favorably
      to those obtained with acetaminophen. Incubation of AST IV with N-bromoacetyl-4
      hydroxyphenylamine at pH 7.0 in the absence of PAPS and other substrates resulted
      in an irreversible inactivation of the enzyme that was both time- and
      concentration-dependent. [14C]-N-bromoacetyl-4-hydroxyphenylamine was synthesized
      and used to analyze the regions of protein sequence that were involved in the
      binding of the affinity label. AST IV was incubated with [14C]-N-bromoacetyl-4
      hydroxyphenylamine, hydrolyzed with endoproteinase Lys-C and the labeled peptides
      were purified by HPLC. Control incubations of AST IV with the affinity label in
      the presence of 4-propylphenol and PAP were utilized to ascertain the specificity
      of the interaction. Sequence analysis of the labeled peptides, carried out by
      automated Edman degradation, revealed labeling sites on cysteine (Cys-232, Cys
      283 and Cys-289) and lysine (Lys-286) residues near the C-terminus of the
      protein. The locations of these labeling sites were further evaluated both by
      sequence-alignment with other sulfotransferases and by theoretical calculations
      on predicted secondary structure.

PMID- 9566736
TI  - Cooperative ligand binding by bovine phenol sulfotransferase.
AB  - Although several phenol sulfotransferases (PSTs) that metabolize hormones and
      xenobiotics have been purified and examined by steady state kinetic methods,
      little is known about ligand binding and subunit interactions in these enzymes.
      Inhibition of a purified recombinant homodimeric bovine PST by 2,6-dichloro-4
      nitrophenol (DCNP) and pentachlorophenol (PCP) displayed very sharp titration
      curves that required modeling with Hill equations with slope factors of 2 and 3,
      respectively. This observation suggested positive cooperative ligand binding
      during catalytic turnover. The binding of PCP was also monitored by intrinsic
      protein fluorescence, which was quenched up to 36% upon saturation with the
      inhibitor. In the absence of 3'-phosphoadenosine-5'-phosphosulfate (PAPS),
      quenching curves were fit with the Hill equation and an interaction factor of 1.
      In contrast, inclusion of PAPS increased the association of PCP and resulted in
      positive cooperative binding with an interaction factor of 1.6-1.9. Whereas
      adenosine-3',5'-diphosphate (PAP) also facilitated cooperative binding of PCP,
      adenosine-5'-monophosphate (AMP) was not effective. This correlated to inhibition
      of PST by PAP, whereas AMP was not inhibitory up to 1 mM. Therefore, occupation
      of the PST nucleotide binding site(s) facilitates a subunit interaction that can
      promote subsequent binding of phenolic ligands.

PMID- 9566737
TI  - A review of the effects of manipulation of the cysteine residues of rat aryl
      sulfotransferase IV.
AB  - Aryl sulfotransferase IV from rat liver has the broad substrate range that is
      characteristic of the enzymes of detoxication. With the standard assay
      substrates, 4-nitrophenol and 3'-phosphoadenosine 5'-phosphosulfate (PAPS),
      sulfation is optimum at pH 5.4 whereas the reaction is minimal in the
      physiological pH range. These properties preclude a physiological function for
      this cytosolic enzyme. Partial oxidation of the enzyme, however, results not only
      in an increase in the rate of sulfation but also in a shift of the pH optimum to
      the physiological pH range. The mechanism for this dependence on the redox
      environment involves oxidation at Cys66, the cysteine residue that is conserved
      throughout the phenol sulfotransferase family. As documented by mass
      spectroscopic methods, oxidation by GSSG leads to the formation of an internal
      disulfide between Cys66 and Cys232; for mutants at Cys232, the oxidation product
      is a mixed disulfide of Cys66 and glutathione. Both of these disulfide species
      activate the enzyme and allow it to function at a pH optimum in the physiological
      range. The activated enzyme differs from the reduced form by a more circumscribed
      substrate spectrum. All five mutants, in which each of the cysteines of the
      sulfotransferase subunit have been changed to serine, are catalytically active.
      Only Cys66 is required for the redox response.

PMID- 9566738
TI  - Recent developments in the study of the structure-function relationship of
      flavonol sulfotransferases.
AB  - With the rapid proliferation of sulfotransferase (ST) cDNA sequences in the last
      5 years, consensus sequences were identified in four conserved regions. The
      association of these regions with substrate binding or catalysis was tested in
      several site-directed mutagenesis studies. Due to their strict substrate and
      position specificities, the flavonol 3- and 4'-STs represent an advantageous
      model system for the study of the structure-function relationship of cytosolic
      STs. Using a combination of chimeric and site-directed mutant proteins, a domain
      was identified containing all the determinants responsible for the substrate
      specificity of these enzymes, and characterized amino acid residues conserved in
      all cloned STs that are involved in substrate binding and catalysis. This paper
      summarizes the results of these studies.

PMID- 9566739
TI  - Structural and functional characterisation of human sulfotransferases.
AB  - The human aryl sulfotransferases HAST4 and HAST4v vary by only two amino acids
      but exhibit markedly different affinity towards the sulfonate acceptor p
      nitrophenol and the sulfonate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS).
      To determine the importance of each of these amino acid differences, chimeric
      constructs were made of HAST4 and HAST4v. By attaching the last 120 amino acids
      of HAST4v to HAST4 (changing Thr235 to Asn235) we have been able to produce a
      protein that has a Km for PAPS similar to HAST4v. The reverse construct, HAST4v/4
      produces a protein with a Km for PAPS similar to HAST4. These data suggests that
      the COOH-terminal of sulfotransferases is involved in co-factor binding.

PMID- 9566740
TI  - Effects of 3'-phosphoadenosine 5'-phosphate on the activity and folding of phenol
      sulfotransferase.
AB  - Known spectroscopic and kinetic data are used to formulate pathways of the
      physiological and transfer reactions and the substrate inhibition of phenol
      sulfotransferase. Kinetic mechanisms indicate that release of PAP from enzyme
      complex is required for the physiological reaction but not for the transfer
      reaction. The pathways explain rate difference between the physiological and
      transfer reactions since the release of PAP is the rate-limiting step of the
      former reaction. Two enzyme species of phenol sulfotransferase which distinguish
      the physiological and transfer reaction were found to involve the binding of PAP.
      Differences between two forms of phenol sulfotransferase, alpha and beta,
      indicate that they assemble through different folding process. It is demonstrated
      that only alpha enzyme renatures in the presence of PAP and beta enzyme renatures
      only in the absence of PAP in vitro. In the over-expressed system, formation of
      alpha and beta phenol sulfotransferase is also dependent on the availability of
      PAP in Escherichia coli. It is concluded that folding of phenol sulfotransferase
      is assisted by PAP to form alpha enzyme. In the absence of PAP, beta form of
      phenol sulfotransferase is produced.

PMID- 9566741
TI  - Bacterial expression of two human aryl sulfotransferases.
AB  - The effect of replacing a single codon in the N-terminal of human aryl
      sulfotransferase (HAST) 1 and 3 with one that is more commonly found in E. coli
      genes was assessed. The pKK233-2 E. coli expression vector was employed and the
      polymerase chain reaction (PCR) was used to introduce the 5' nucleotide
      substitution, at the same time maintaining the fidelity of the amino acid
      sequence. The data indicates that this change had a minimal effect on protein
      production, subcellular localization or, in the case of HAST3, catalytic
      activity. In general, the pKK233-2 E. coli vector has been less than optimal for
      expressing human sulfotransferase cDNAs.

PMID- 9566742
TI  - Sulfate activation and transport in mammals: system components and mechanisms.
AB  - Extensive studies on the mammalian sulfate-activating enzymes and PAPS
      translocase have enhanced our understanding of the overall pathway of sulfate
      activation and utilization. Isolation of the PAPS-synthesizing activities from
      rat chondrosarcoma and preparation of stable non-hydrolyzable analogs of APS and
      PAPS have facilitated the kinetic characterization of mammalian ATP sulfurylase
      and APS kinase. These studies provided the basis for further experimental work
      showing that APS, the labile intermediate product, is channeled directly between
      the sulfurylase and kinase active sites. The defect in the brachymorphic mutant
      mouse lies in this channeling mechanism, thus interfering with efficient PAPS
      production. The rat chondrosarcoma ATP sulfurylase and APS kinase activities, in
      fact, reside in a single bifunctional cytoplasmic protein, which has now been
      cloned and expressed. The mechanism by which PAPS reaches its sites of
      utilization in the Golgi lumen has also been elucidated: The PAPS translocase is
      a 230-kDa integral Golgi membrane protein which functions as an antiport.

PMID- 9566743
TI  - Redefining reductive sulfate assimilation in higher plants: a role for APS
      reductase, a new member of the thioredoxin superfamily?
AB  - The reaction steps leading from the intermediate adenosine 5'-phosphosulfate
      (APS) to sulfide within the higher plant reductive sulfate assimilation pathway
      are the subject of controversy. Two pathways have been proposed: a 'bound
      intermediate' pathway in which the sulfo group of APS is first transferred by APS
      sulfotransferase to a carrier molecule to form a bound sulfite intermediate and
      is then further reduced by thiosulfonate reductase to bound sulfide; and a 'free
      intermediate' pathway in which APS is further activated to 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) by APS kinase followed by reduction of the sulfo group to
      free sulfite by PAPS reductase. Sulfite is then reduced to free sulfide by
      sulfite reductase. Sulfide, either free or bound, is then incorporated into
      organic form (as cysteine) by the enzyme O-acetylserine (thiol) lyase. In order
      to better characterize the pathway we attempted to clone PAPS reductase cDNAs by
      functional complementation of an Escherichia coli cysH mutant to prototrophy. We
      found no evidence for PAPS reductase cDNAs but did identify cDNAs that encode a
      small family of novel, chloroplast-localized proteins with APS reductase activity
      that are new members of the thioredoxin superfamily. We show here that the
      thioredoxin domain of these proteins is functional. We speculate that rather than
      proceeding via either of the pathways proposed above, reductive sulfate
      assimilation proceeds via the reduction of APS to sulfite by APS reductase and
      the subsequent reduction of sulfite to sulfide by sulfite reductase. In this
      scheme the product of the APS kinase reaction, PAPS, is not a direct intermediate
      in the pathway but rather acts as a substrate for sulfotransferase action and
      perhaps as a store of activated sulfate that can be returned to the pathway as
      APS via phosphohydrolase action on PAPS. Interactions between enzyme isoforms
      within the chloroplast stroma may bring about substrate channeling of APS and
      contribute to the partitioning of APS between sulfotransferase reactions on the
      one hand and the synthesis of cysteine and related metabolites via the reductive
      sulfate assimilation pathway on the other.

PMID- 9566744
TI  - Microsomal steroid sulfatase: interactions with cytosolic steroid
      sulfotransferases.
AB  - Net sulfation of 4-methylumbelliferone in intact hepatocytes is regulated, in
      part, by substrate cycling between sulfotransferases (SULT) and arylsulfatases
      (ARS). Thus, ARS have the potential to influence rates of net sulfate conjugation
      of a variety of compounds in intact cells via interaction with SULT. Unlike ARSA
      and ARSB, which are lysosomal, steroid sulfate sulfatase (ARSC, also known as
      STS) is localized exclusively in the endoplasmic reticulum (ER). The present
      study was designed to assess the existence and extent of substrate cycling
      between steroids and their sulfate conjugates through ARSC and SULT, and also to
      initiate studies of the topology of the catalytic site of ARSC in the rat liver
      ER. Addition of rat liver microsomes to cytosol and 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) reduced rates of sulfation of dehydroepiandrosterone (DHEA)
      by SULT, and similarly hydrolysis of DHEA sulfate (DHEAS) was reduced when
      recombinant human hydroxysteroid SULT was added to rat liver microsomes in the
      presence of PAPS. There was no evidence for ARSC latency in the presence of
      detergent at either 4 or 37 degrees C, indicating that facilitated transport of
      steroid sulfates across the ER membrane may not be required for ARSC activity.
      The effect of proteases on ARSC activity in intact and disrupted microsomes was
      determined and compared with effects on components of the glucose-6-phosphatase
      system known to be localized on the lumenal and cytoplasmic surfaces of the ER.
      In contrast to the components of the glucose-6-phosphatase system, activity of
      ARSC in both intact and disrupted microsomes was substantially more resistant to
      protease inactivation. Our results indicate that substrate cycling of steroids
      and their sulfates does occur, and suggest that the active site of ARSC may be
      located within the ER membrane.

PMID- 9566745
TI  - Steroid sulphatase: expression, isolation and inhibition for active-site
      identification studies.
AB  - Steroid sulphatase, which can hydrolyse 3-hydroxysteroid sulphates, has important
      roles in several physiological and pathological processes. A number of steroid
      sulphatase inhibitors have now been developed, of which the most potent to date
      is oestrone-3-O-sulphamate (EMATE). This inhibitor inactivates steroid sulphatase
      in an irreversible, time- and concentration-dependent manner. In order to be able
      to use a radiolabelled derivative of EMATE to study the active site, it will be
      essential to prepare the steroid sulphatase in a pure form. For this, attempts
      have been made to express the protein, using the steroid sulphatase cDNA, in the
      pGEX2T expression system and also to express a mutant form of the protein, in
      which the putative membrane-spanning domain was deleted, in CHO cells. In
      addition, a soluble steroid sulphatase has been identified from the snail Helix
      pomatia. This steroid sulphatase is inhibited by EMATE in an irreversible manner,
      similar to the human steroid sulphatase and appears to possess a histidine
      residue at its active site. The expression and/or isolation of a steroid
      sulphatase, in conjunction with the use of a radiolabelled derivative of EMATE
      should allow important new information about the active site of this enzyme and
      the mechanism of its inactivation to be obtained.

PMID- 9566746
TI  - Sulfotransferase-mediated activation of mutagens studied using heterologous
      expression systems.
AB  - Sulfation is a common final step in the biotransformation of xenobiotics and is
      traditionally associated with inactivation. However, the sulfate group is
      electron-withdrawing and may be cleaved off heterolytically in some molecules
      leading to electrophilic cations which may form adducts with DNA and other
      important cellular structures. Since endogenous sulfotransferases do not appear
      to be expressed in indicator cells of standard mutagenicity tests, rat and human
      sulfotransferases have been stably expressed in his- Salmonella typhimurium
      strain TA1538 and Chinese hamster V79 cells. Using these recombinant indicator
      cells, sulfotransferase-dependent genotoxic activities were detected with N
      hydroxy-2-acetylaminofluorene, 2-acetylaminofluorene (in the presence of co
      expressed rat cytochrome P450 1A2), hycanthone, 1'-hydroxysafrole, alpha
      hydroxytamoxifen and various benzylic alcohols derived from polycyclic aromatic
      hydrocarbons. In several cases, it was critical that the reactive sulfuric acid
      conjugates were formed directly within the indicator cells, owing to the
      inefficient penetration of cell membranes. In other cases, spontaneous benzylic
      substitution reactions with medium components, such as halogenide ions or amino
      acids, led to secondary, membrane-penetrating reactive species. Different
      sulfotransferases, including related forms from rat and human, substantially
      differed in their substrate specificity towards the investigated promutagens. It
      is known that some sulfotransferases are expressed with high tissue and cell type
      specificities. This site-dependent expression together with the limitations in
      the distribution of reactive sulfuric acid conjugates may explain organotropic
      effects of compounds activated by this metabolic pathway.

PMID- 9566747
TI  - Bioactivation of benzylic and allylic alcohols via sulfo-conjugation.
AB  - Although sulfo-conjugation, in general, has been regarded as a detoxification
      process in the xenobiotic metabolism, there is a substantial body of data
      supporting that the same reaction can also lead to activation of certain types of
      chemical carcinogens and mutagens. Examples include some aromatic amines and
      amides, alkenylbenzenes, methyl-substituted polyaromatic hydrocarbons,
      nitrotoluenes and nitrosamines. The N- or O-hydroxy derivatives of these
      compounds undergo sulfonation to form extremely reactive sulfuric acid esters
      that can play a role as ultimate carcinogenic/mutagenic metabolites. Previous
      studies from several laboratories have shown that hydroxymethyl polyarenes, such
      as hydroxymethylbenz[a]anthracenes, 6-hydroxymethylbenzo[a]pyrene, and 1
      hydroxymethylpyrene, are activated to reactive benzylic sulfuric acid esters,
      preferentially by rat hepatic hydroxysteroid sulfotransferase. Some aromatic
      hydrocarbons bearing the secondary benzylic hydroxy functionality can also yield
      electrophilic sulfate esters in the presence of hepatic sulfotransferase
      activity. Thus, benzylic mono- and dihydroxy derivatives of cyclopenta[cd]pyrene
      form mutagenic and DNA binding species when incubated with rat liver cytosol and
      the sulfo-group donor, 3'-phosphoadenosine-5'-phosphosulfate. 1-Hydroxy-3
      methylcholanthrene that also possesses the cyclopenta-fused ring system appears
      to be metabolically activated through sulfo-conjugation. Likewise, benzo[a]pyrene
      tetraol might be activated through sulfuric acid esterification at one of two
      benzylic hydroxyl groups. Methylene-bridged polyarenols represent another
      potential group of cyclic secondary benzylic alcohols that can be activated by
      sulfotransferases. Certain non-polycyclic aromatic type benzylic alcohols have
      also been proposed to undergo sulfotransferase-mediated activation. Besides
      benzylic sulfonation, sulfuric acid esterification of certain allylic alcohols
      can produce reactive species.

PMID- 9566748
TI  - Genetic polymorphisms in human liver phenol sulfotransferases involved in the
      bioactivation of N-hydroxy derivatives of carcinogenic arylamines and
      heterocyclic amines.
AB  - Three related forms of phenol sulfotransferase (PSULT), thermostable ST1A2
      (SULT1A2hum) and ST1A3 (SULT1A1hum) and a thermolabile TL-PST (SULT1A3hum), are
      known to exist in human livers. Thermostable forms, whose activities are
      polymorphically distributed, have been shown to mediate the bioactivation of
      carcinogenic N-hydroxy arylamines and heterocyclic amines. To clarify the nature
      of the sulfation polymorphism, the study compared the expressed levels of ST1A2,
      ST1A3 and TL-PST mRNAs in human livers by the method of reverse-transcriptase
      polymerase chain reaction (RT-PCR), utilizing HindIII, BamHI and SnaBI sites
      which were unique to the above PSULT cDNAs, respectively. Of the PCR products
      derived from human liver (n = 26), 43-89, < 1-29 and < 1-21% showed the
      restriction pattern characteristic for ST1A3, ST1A2 and TL-PST cDNAs,
      respectively, thus indicating that ST1A3 mRNA is the major transcript. Hepatic p
      nitrophenol and dopamine sulfation rates ranged from 440-2670 and < 5-460
      pmol/min per mg protein in the 26 individuals, respectively. The observed
      differences in the ST1A3 and TL-PST mRNA levels were consistent with the
      differences in p-nitrophenol and dopamine sulfations. Relative levels of hepatic
      ST1A3 mRNA were non-normally distributed and correlated significantly with p
      nitrophenol sulfation. In addition, variant forms of ST1A3 mRNA encoding
      Arg213His and Met223Val were detected in human livers. With regard to Arg213His,
      28 individuals who had homozygous 213Arg alleles, 15 individuals who were
      heterozygotes and nine homozygous 213His individuals were found by a newly
      established genotyping method among 52 human liver samples. Frequency of 223Val
      allele was apparently lower than that of 213His allele, as no homozygous 223Val
      individual and only three individuals who were heterozygotes (223Met/Val) were
      observed among 52 individuals. These results suggest that regulation of p
      nitrophenol sulfation occurs at the level of gene transcription of ST1A3 which is
      the major transcript of the three PSULT mRNAs and that a polygenic basis for the
      apparent genetic polymorphism of sulfation was likely because of the existence of
      ST1A3 variants.

PMID- 9566749
TI  - Expression of human estrogen sulfotransferase in Salmonella typhimurium:
      differences between hHST and hEST in the enantioselective activation of 1
      hydroxyethylpyrene to a mutagen.
AB  - Various human sulfotransferases (hP-PST, hM-PST, hHST) and rat sulfotransferases
      (rPST-IV, rHSTa) have already been expressed in Ames' Salmonella strains (in
      particular in TA1538). Now a further strain, TA1538-hEST, which expresses the
      human estrogen sulfotransferase (hEST), has been constructed. This strain
      activated the primary benzylic alcohol 1-hydroxymethylpyrene (1-HMP) and the
      secondary benzylic alcohol 1-hydroxyethylpyrene (1-HEP) to mutagens. Human
      sulfotransferases hEST and hHST both activated 1-HEP, but they differed
      substantially in their enantioselectivity for this compound.

PMID- 9566750
TI  - Inhibitory effect of hemin on mutagenicity of the electrophilic sulfuric acid
      ester of 6-hydroxymethylbenzo[a]pyrene.
AB  - In the present study, we examined the effects of hemin on the mutagenicity of 6
      sulfooxymethylbenzo[a]pyrene (SMBP) in Salmonella typhimurium TA98 and Chinese
      hamster lung fibroblast (V79) cells. The compound was tested for the possible
      chemoprotective activity against mutagenesis induced by SMBP and its precursor, 6
      hydroxymethylbenzo[a]pyrene (HMBP), activated by hepatic cytosol and PAPS in S.
      typhimurium TA98. Hemin not only inhibited the mutagenic activity of SMBP in V79
      cells but repressed the cytotoxicity induced by this reactive ester as
      demonstrated by increased cell growth. The intracellular accumulation of
      radioactivity in V79 cells exposed to [3H]SMBP was reduced by approximately 50%
      when hemin (10 microM) was added to the medium. Likewise, the formation of SMBP
      DNA adducts in these cells was significantly attenuated by treatment with hemin.
      The covalent complex formation of hemin with SMBP was confirmed by solvent
      extraction and reverse-phase HPLC.

PMID- 9566751
TI  - Inhibition of androgen action by dehydroepiandrosterone sulfotransferase
      transfected in PC-3 prostate cancer cells.
AB  - Age-dependent loss of androgen sensitivity of the rat liver is associated with a
      marked increase in dehydroepiandrosterone/hydroxysteroid sulfotransferase (rStd)
      activity. Sulfonated steroid hormones are known to be ineffective in binding
      receptor proteins. These observations suggest that intracellular androgen
      sulfonation can physiologically influence androgen action. We have examined the
      inhibitory effect of rStd on androgen action in the human prostate cancer-derived
      PC-3 cells transfected with the rat androgen receptor (AR) expression plasmid and
      two androgen-responsive promoter reporter constructs (murine mammary tumor long
      terminal repeat ligated to chloramphenicol acetyltransferase (CAT) gene and rat
      probasin androgen response element (ARE) ligated to firefly luciferase (LUC)
      gene). These transfected cells were dependent on 5alpha-dihydrotestosterone (DHT)
      for the activation of both reporter genes and showed about a 200- and a 800-fold
      increase of CAT and LUC activity, respectively, at 10(-10) M DHT over the no
      hormone control. Expression of the sulfonating enzyme in this cell transfection
      system via the rStd expression plasmid caused a dose-dependent decline in the
      reporter activity with approximately 90% inhibition of androgen action at a
      rStd:AR plasmid ratio of 100. From these results we conclude that irrespective of
      a high level of AR, changes in the Std expression can markedly alter the androgen
      sensitivity of target cells.

PMID- 9566752
TI  - Characterization of thyroid hormone sulfotransferases.
AB  - Sulfation is an intriguing pathway of thyroid hormone metabolism since it
      facilitates the degradation of the hormone by the type I deiodinase (D1). This
      study reports the preliminary characterization of iodothyronine sulfotransferase
      activities of rat and human liver cytosol and recombinant rSULT1C1 and hSULT1A1
      isoenzymes. All these enzyme preparations catalyzed the sulfation of--in
      decreasing order of efficiency--3,3'-diiodothyronine (3,3'-T2) > 3,3',5
      triiodothyronine (T3) approximately 3,3',5'-triiodothyronine (rT3) > thyroxine
      (T4). 3,3'-T2 sulfotransferase activity was found to be higher in male than in
      female rat liver, which has also been shown by others for the expression of
      rSULT1A1 and rSULT1C1. No sulfation of iodothyronines was observed with rSULT1A1.
      Different phenol derivatives were found to be potent inhibitors of the sulfation
      of 3,3'-T2 by native and recombinant sulfotransferases, with pentachlorophenol
      and 2,4,6-tribromophenol being the most potent. The inhibitions exerted by the
      different phenols on 3,3'-T2 sulfation by rSULT1C1 correlated better with the
      effects observed in male than with those in female liver. A strong correlation
      was also observed between the inhibition profiles of human liver cytosol and
      hSUL1T1A1. These results suggest that: (1) rSULT1C1 is an important isoenzyme for
      the sulfation of thyroid hormone in male rat liver; (2) another isoenzyme with
      similar properties, perhaps rSULT1B1, is responsible for thyroid hormone
      sulfation in female rat liver and may also contribute to this process in male rat
      liver; and (3) hSULT1A1 is an important isoenzyme for thyroid hormone sulfation
      in human liver.

PMID- 9566753
TI  - Inhibition of thyroid hormone sulfation by hydroxylated metabolites of
      polychlorinated biphenyls.
AB  - In this study we investigated the possible inhibitory effects of hydroxylated
      metabolites of polychlorinated biphenyls (OH-PCBs) on iodothyronine
      sulfotransferase activity. The results indicate that OH-PCBs are potent
      inhibitors of this activity in vitro, with IC50 concentrations in the low micro
      molar range. Inhibition of sulfotransferase activity towards 3,3'-diiodothyronine
      (T2) was similar to that towards 3,3',5-triiodothyronine (T3) in this in vitro
      assay, therefore, T2 can be used as the model substrate for the active hormone
      T3. An important structural requirement for T2 sulfotransferase inhibition is a
      hydroxyl group on the para or meta position of the OH-PCBs. Since T3 is the
      active hormone, playing a very important role in somatic and brain development
      and since hydroxylated PCBs can accumulate in fetuses, inhibition of T3 sulfation
      could be a possible mechanism for the developmental neurotoxicity of PCBs.

PMID- 9566754
TI  - Regulation of sulfotransferase mRNA expression in male and female rats of various
      ages.
AB  - Sulfotransferases (SULTs) are Phase II drug-metabolizing enzymes that catalyze
      the addition of a sulfuryl moiety to both endogenous compounds, including
      steroids and neurotransmitters, and certain xenobiotics, including N-hydroxy-2
      acetylaminoflourine and phenolic compounds, like alpha-naphthol. In contrast to
      certain Phase I drug-metabolizing enzymes, little is known about the regulation
      of the sulfotransferases. These series of studies were designed to analyze SULT
      mRNA expression and hormonal regulation in male and female rats. The hepatic
      expression of six different SULT isoforms was examined including three phenol
      SULTs and three hydroxysteroid SULTs. SULT mRNA expression was examined in adult
      and developing rats, as well as, in hypophysectomized (HX) and growth hormone
      supplemented HX animals. SULT1A1 is thought to be important for the sulfation of
      simple phenols and its mRNA expression is about twice as high in adult male as in
      female rats. This difference in SULT1A1 mRNA levels is largely due to a greater
      decrease in mRNA levels after puberty in female than in male rats. Hypophysectomy
      resulted in a decrease in expression of SULT1A1 mRNA in both male and female
      rats. Replacement of growth hormone (GH) by either intermittent injection (male
      pattern) or infusion (female pattern) failed to restore SULT1A1 expression.
      Sulfotransferase SULT1C1 has been implicated in activation of N
      hydroxyacetylaminoflourine. In contrast to SULT1A1, SULT1C1 mRNA expression is
      about 10-fold higher in adult males than in adult female rats. This male-dominant
      expression pattern emerges at 40-50 days of age and is due to an increase in
      SULT1C1 mRNA in males. Hypophysectomy abolished SULT1C1 expression in male rats.
      Interestingly, replacement of GH by injection (male pattern) restored SULT1C1
      mRNA expression in males and enhanced SULT1C1 expression in female rats to levels
      observed in adult male rats. GH infusion (female pattern) did not affect SULT1C1
      mRNA expression in either male or female rats. Estrogen sulfotransferase
      (SULT1E2) may play a role in estrogen homeostasis. Adult male rats express
      SULTIE2 mRNA at levels 10-fold higher than those observed in adult females and
      similar to SULT1C1, this is due to an increase in SULT1E2 mRNA occurring during
      puberty in the male rat. Hypophysectomy did not appreciably affect SULT1E2
      expression in male rats, however in contrast to males, hypophysectomy markedly
      enhanced SULT1E2 expression in female rats. GH infusion suppressed SULT1E2 levels
      in HX male rats. The expression of hydroxysteroid sulfotransferases was also
      examined. The SULT-20/21 isoform was expressed in both male and female rats. Male
      expression of this isoform peaked at 30 days of age and then declined to
      approximately 30% of the level observed in adult females. SULT-20/21 mRNA
      expression increased sharply at 45 days of age in female rats and remained
      elevated. Expression of SULT-20/21 mRNA was decreased markedly by hypophysectomy
      in both male and female rats. GH injection did not affect SULT-20/21 mRNA
      expression in HX males, however this treatment resulted in a 4-fold increase in
      SULT-20/21 mRNA in HX females. GH infusion restored SULT-20/21 expression in HX
      male rats. GH infusion did elevate SULT-20/21 mRNA expression in female-HX rats,
      but not to the level observed in intact females. Hydroxysteroid SULT isoform SULT
      40/41 was expressed in adult female but not adult male rats. SULT-40/41
      expression peaked at 15 days of age in both male and female rats and decreased
      thereafter. The decrease in expression was more pronounced in male rats. SULT-60
      mRNA, like SULT-40/41, was expressed only in adult female rats. Male rats express
      SULT-60 at 30 days of age, but SULT-60 mRNA is undetectable at 60 days. SULT-60
      mRNA was expressed in females only after day 30 and female SULT-60 mRNA
      expression remains high thereafter. SULT-40/41 and SULT-60 mRNA expression was
      increased by HX in male rats and decreased by HX in female rats. (ABSTRACT
      TRUNCATED)

PMID- 9566755
TI  - Regulation of sulfotransferase gene expression by glucocorticoid hormones and
      xenobiotics in primary rat hepatocyte culture.
AB  - In the rat liver, hydroxysteroid sulfotransferase-a (HST-a) and aryl
      sulfotransferase IV (ASTIV) represent two major rat hepatic sulfotransferases
      that are important to xenobiotic metabolism. Prototypic CYP1A1 and CYP2B/3A
      inducers regulate rat hepatic sulfotransferase gene expression although not
      necessarily in a coordinate direction. It has been previously reported that in
      vivo treatment with CYP1A1 inducer 3-methylcholanthrene (3-MC) suppresses rat
      hepatic HST-a mRNA expression in a dose-dependent manner. Similarly, HST-a and
      ASTIV mRNA levels become suppressed or induced, respectively, following in vivo
      treatment with phenobarbital (PB)-like CYP2B/3A inducers or prototypic CYP3A
      inducers such as glucocorticoid hormones. In the whole animal, sulfotransferase
      gene expression is modulated by members of the hypothalamic/pituitary-adrenal
      gonadal hormone axis. However, studies in primary rat hepatocyte culture suggest
      that prototypic P450 inducers regulate HST-a and ASTIV gene expression directly
      at the level of the hepatocyte. Glucocorticoid-mediated sulfotransferase
      expression was compared with the regulation of tyrosine amino transferase (TAT),
      a gene that is transcriptionally regulated by ligand bound glucocorticoid
      receptor. It was found that lower doses of dexamethasone (DEX, 10(-7) M) produced
      concomitant increases in ASTIV and TAT mRNA expression, whereas HST-a mRNA
      expression continued to rise as the DEX dose was increased through 10(-5) M. When
      hepatocytes were co-incubated with DEX and antiglucocorticoid/antiprogestin RU
      486, DEX-stimulated HST-a mRNA expression was not significantly inhibited by RU
      486, but ASTIV and TAT mRNA expression were inhibited to a similar extent. The
      results suggested that ASTIV, like TAT, is likely regulated by a classical
      glucocorticoid receptor mediated mechanism, whereas HST-a is probably regulated
      by glucocorticoids via an alternative mechanism. In contrast to the positive
      effects of glucocorticoid hormones, HST-a and ASTIV mRNA expression was
      negatively regulated by xenobiotics such as PB-like CYP2B/3A inducers or aryl
      hydrocarbon receptor (AhR) agonist CYP1A1 inducers. Incubation of primary
      cultured rat hepatocytes with PB or structurally dissimilar PB-like inducers
      clotrimazole, diphenylhydantoin, heptachlor, gamma-hexachlorocyclohexane or
      2,2',4,4',5,5'-hexachlorobiphenyl suppressed HST-a and ASTIV mRNA levels. Also,
      incubation of primary cultured rat hepatocytes with CYP1A1 inducer beta
      naphthoflavone or with archetypic AhR agonist, 2,3,7,8-tetrachloro-p-dioxin
      (TCDD) markedly suppressed HST-a and ASTIV mRNA expression. These data suggest
      that the rat HST-a and ASTIV genes are positively regulated by glucocorticoid
      hormones and negatively regulated by xenobiotics as a result of molecular and
      cellular mechanisms that act directly on the hepatocyte.

PMID- 9566756
TI  - Identification and characterization of cytosolic sulfotransferases in normal
      human endometrium.
AB  - Understanding the factors which alter estrogen metabolism and activity in
      endometrial tissue is important because unopposed estrogen stimulation is an
      important risk factor in the development of endometrial carcinoma. The cyclic
      progression of the endometrium through proliferative and secretory phases is
      normally under the control of the ovarian hormones beta-estradiol (E2) and
      progesterone. One mechanism by which progesterone inhibits the activity of E2 in
      secretory endometrium is by elevating the degree of E2 sulfation, thereby
      reducing its ability to bind to the estrogen receptor and elicit a cellular
      response. Our laboratories have investigated the cytosolic sulfotransferases
      (STs) found in biopsies of both proliferative and secretory endometrium obtained
      from five normal pre-menopausal women who were not taking any drugs or steroids.
      Two of the human cytosolic STs were detected in human endometrial tissues. The
      phenol-sulfating form of phenol ST (P-PST) was found at varying levels in cytosol
      from both proliferative and secretory endometrium in all of the women studied but
      with no consistent correlation to the phase of the menstrual cycle. In contrast,
      estrogen ST (EST) was not detected in the proliferative endometrial cytosol of
      any of the women studied but was consistently found in all of the secretory
      endometrial cytosols. The presence and levels of these STs was confirmed by ST
      activity studies, immunoblot analysis and Northern blot analysis. These results
      indicate that the expression of EST in human endometrial tissues varies with the
      phase of the menstrual cycle and is most likely regulated by progesterone
      secreted from the ovaries.

PMID- 9566757
TI  - Localisation of aryl sulfotransferase expression in human tissues using
      hybridisation histochemistry and immunohistochemistry.
AB  - To date, the laboratory has cloned seven unique human sulfotransferases; five
      aryl sulfotransferases (HAST1, HAST2, HAST3, HAST4 and HAST4v), an estrogen
      sulfotransferase and a dehydroepiandrosterone sulfotransferase. The cellular
      distribution of human aryl sulfotransferases in human hepatic and extrahepatic
      tissues has been determined using the techniques of hybridization histochemistry
      and immunohistochemistry. Human aryl sulfotransferase expression was detected in
      liver, epithelial cells of the gastrointestinal mucosal layer, epithelial cells
      lining bronchioles and in mammary duct epithelial cells.

PMID- 9566758
TI  - Specificity of the T-cell responses in covalently linked peptides each comprising
      of a T helper epitope.
AB  - The selection of T-cell specificities in chimeric peptides comprising of two T
      helper epitopes (288-302 and 240-252) from the fusion protein of measles virus
      was investigated. The resulting chimeric peptides (288-P-240 and 240-P-288) were
      shown to be immunogenic by inducing proliferative responses in both B10.s and
      C57BL/6 strains of mice. In B10.s mice immunization with the chimeric peptides
      resulted in proliferative T-cell responses only to the constituent 288-302
      peptide, whereas in C57BL/6 mice no proliferative responses to the constituent
      288-302 or 240-252 peptides were detected. In vivo competition studies between
      the 288-302 and 240-252 peptides for binding to the I-As molecule have shown that
      the peptide 288-302 was dominant in B10.s mice and competed with the non-dominant
      240-252 peptide for the induction of an in vivo response. The absence of any
      proliferative T-cell response to the constituent 288-302 and 240-252 peptides
      after immunization of C57BL/6 mice with the 288-P-240 or 240-P-288 chimeric
      peptides, suggests that the dominant T-cell responses might have shifted to newly
      formed T cell epitope(s) as a result of the covalent linkage of the two peptides.
      In conclusion, these results indicate that the selection of Th epitopes within
      chimeric peptides is dependent not only on the amino acid composition of the
      epitope but also on the context of the epitope within the chimera and the
      haplotype of the mouse strain used.

PMID- 9566759
TI  - Induction of cross-reactive antibodies against a self protein by immunization
      with a modified self protein containing a foreign T helper epitope.
AB  - Self proteins are handled in the same way as foreign proteins by antigen
      presenting cells, but because of T-cell tolerance the presentation of self
      peptides does not normally lead to T cell activation. By providing physically
      linked T-cell help it is possible to overcome the B cell non-responsiveness
      toward self antigens. We have shown previously that a very potent antibody
      response, cross-reactive with a self protein, can be rapidly induced by
      immunizing with a recombinant immunogen consisting of the self protein with a
      foreign immunodominant T helper epitope inserted into its sequence (Dalum, I.,
      Jensen, M. R., Hindersson, P., Elsner, H. I. and Mouritsen, S. (1996) J.
      Immnunol. 157, 4796). In this study we compare this approach for inducing
      autoantibodies against a self protein with the traditional method of conjugating
      the self antigen to a foreign carrier protein. The highly conserved self protein
      ubiquitin with an inserted epitope from ovalbumin (UbiOVA) is used as a model
      protein and compared to two traditionally conjugated immunogens consisting of
      ubiquitin chemically conjugated to a peptidic T helper epitope or to ovalbumin.
      The traditionally conjugated immunogens induce much slower and low titered
      ubiquitin specific antibody responses than the recombinant construct which also
      is capable of inducing antibodies directed against a much broader range of
      potential ubiquitin B cell determinants than the chemically conjugated
      immunogens. All three constructs are processed by antigen presenting cells and
      ovalbumin derived T cell epitopes are presented to T helper cells. From these
      observations it seems likely that the presence of non-shielded autologous B cell
      determinants on the immunogen is critical for the ability to induce a strong
      autoantibody response with a diverse fine specificity. Furthermore, the ubiquitin
      specific antibodies induced by UbiOVA contain higher levels of IgG2a/b relative
      to IgG1 compared to the conjugates. We therefore speculate that the insertion of
      a T cell epitope directly into the self antigen could possibly induce an immune
      response with a different Th1/Th2 balance than a response induced with
      traditional conjugates.

PMID- 9566760
TI  - Comparison of llama VH sequences from conventional and heavy chain antibodies.
AB  - Forty different PCR clones encoding a llama variable heavy chain domain were
      analysed. The majority of these clones are derived from heavy-chain antibody cDNA
      in which the entire CH1 exon is absent. It appears from the amino acid within the
      VHH framework 1 and 3 that all the llama clones belong to the VH III family.
      However, the individual llama VHH sequences differ more substantially from each
      other than expected for members of the same family. Several remarkable amino acid
      substitutions in the framework 2 hinder the proper association of the VL.
      However, they lay the foundation for the secretion from the endoplasmic reticulum
      and good solubility behaviour of llama H2 antibodies. The repertoire of the llama
      VHHs may be extensive due to the presence of a long CDR3-loop, often constrained
      by a disulfide bridge and the occurrence of H1 and H2 loop conformations not yet
      encountered in mice or human VHs. The variability plot of the amino acids in the
      VHH shows that the first hypervariable region coincides with the structural H1
      loop in contrast to the situation found in mice and man where the CDR1 and H1 are
      slightly offset. We propose that the amino acids of the llama H1 loop participate
      actively in the antigen binding. All these observations are characteristic for
      the llama VHHs of the homodimeric heavy-chain H2 antibodies, but are not
      maintained in the llama clones from conventional heterotetrameric H2L2
      immunoglobulins.

PMID- 9566761
TI  - Contribution of peptide backbone atoms to binding of an antigenic peptide to
      class I major histocompatibility complex molecule.
AB  - Antigenic peptides are thought to bind to class I major histocompatibility
      complex (MHC) molecules through three modes of interaction: van der Waals
      interaction and, to a lesser extent, hydrogen bonding of anchor side chain atoms
      to residues comprising the binding pockets of the MHC molecule; hydrogen bonding
      of N- and C-termini to residues at the ends of the binding groove; and hydrogen
      bonding of peptide backbone atoms to residues lining the binding groove. To
      dissect the relative contribution of each of these interactions to class I MHC
      peptide stability, a retro inverso (RI) analog of VSV-8. an H-2Kb restricted
      cytotoxic T lymphocyte (CTL) epitope and terminally modified variants of both VSV
      8 and RI VSV-8 were synthesized and their ability to target H-2Kb bearing cells
      for CTL mediated lysis was compared. None of RI VSV-8 analogs elicited lysis of
      target cells by CTL specific for VSV-8 nor did they appear to compete with the
      native peptide for binding to H-2Kb. In contrast, terminally modified VSV-8
      peptides elicited target lysis. These findings suggest that side chain
      topochemistry of the peptide is insufficient for stable peptide binding to H-2Kb;
      rather, hydrogen bonding of the peptide backbone atoms to H-2Kb side chain atoms
      appears to play a major role in the stability of the complex. Computer modeling
      confirmed that none of the RI analogs participate in the extensive hydrogen
      bonding network between the peptide backbone and the MHC molecule seen in the
      native structure.

PMID- 9566762
TI  - Lipopolysaccharide (LPS)-induced IL-6 production by embryonic fibroblasts
      isolated and cloned from LPS-responsive and LPS-hyporesponsive mice.
AB  - Fibroblasts participate in inflammatory processes and non-specific immunity by
      producing cytokines and mediators in response to bacterial lipopolysaccharide
      (LPS). The detailed mechanism of LPS-induced cytokine production by fibroblasts
      has not been sufficiently studied. We isolated murine embryonic fibroblasts (MEF)
      from LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice and
      established MEF cell lines and MEF clones. Primarily cultured MEF, MEF cell lines
      and MEF clones from C3H/HeN mice (MEF.He) expressed interleukin (IL)-6 mRNA and
      produced IL-6 molecules in response to even a very low dose (1 ng/ml) of LPS. By
      contrast, those from C3H/HeJ mice (MEF.HeJ) neither expressed IL-6 mRNA nor
      produced IL-6 in response to 1 ng of LPS per ml, although they expressed IL-6
      mRNA and produced IL-6 in response to high doses (more than 100 ng/ml) of LPS.
      The MEF.He clone, but not the MEF.HeJ clone, expressed IL-6 mRNA in response to
      taxol or ceramide, whereas MEF.HeJ clones as well as the MEF.He clone expressed
      IL-6 mRNA in response to IL-1alpha. These results indicate that in the responses
      to LPS, taxol and ceramide, MEF retain the same reactivity as that of the mouse
      strains from which the MEF were derived, and LPS shares the IL-6 signal
      transduction pathway with taxol and ceramide, but not with IL-1. CD14 is not
      relevant to the LPS-induced IL-6 production by MEF, since cloned MEF.He and
      MEF.HeJ were shown not to express CD14 mRNA by Northern blot analysis. No
      difference in LPS-specific binding capacity was shown between the MEF.He and
      MEF.HeJ clones. This finding, together with the fact that hyporesponsiveness of
      MEF.HeJ to LPS was shown at the level of IL-6 mRNA expression, suggests that the
      defect in the LPS-induced IL-6 signal transduction pathway in MEF from C3H/HeJ
      mice is probably located at some site after the LPS-recognition site on the cell
      surface and before transcription of the IL-6 gene.

PMID- 9566763
TI  - Construction and characterisation of a functional CD19 specific single chain Fv
      fragment for immunotherapy of B lineage leukaemia and lymphoma.
AB  - The B cell specific antigen CD19 is a target for the immunotherapy of B lineage
      leukaemias and lymphomas. We have engineered a single chain Fv (scFv) fragment
      from the mouse hybridoma cell line FMC63 which produces monoclonal antibody
      specific for CD19. The genes encoding the FMC63 heavy and light chain variable
      regions were amplified from cDNA and a scFv was constructed by splice overlap
      extension PCR. Analysis of staining of lymphoblastoid cell lines, peripheral
      blood lymphocytes and tonsil sections demonstrated that the monovalent scFv
      fragment has the same cellular specificity as the parent hybridoma antibody.
      Kinetic studies with radiolabelled material showed that the scFv binds target
      cells with a Ka of 2.3 x 10(-9), compared with 4.2 x 10(-9) for the parent
      antibody. This CD19 scFv will be used in experimental models to test its
      therapeutic efficacy and immunogenicity, with a view to application in the
      diagnosis and treatment of human B cell cancers.

PMID- 9566764
TI  - Immunoglobulin as a vehicle for foreign antigenic peptides immunogenic to T
      cells.
AB  - Antibody (Ab) molecules may serve as targeting vehicles for delivery of foreign
      antigenic peptides to antigen presenting cells (APC). An attractive strategy is
      to substitute segments between beta-strands of immunoglobulin (Ig) constant (C)
      region domains with antigenic peptides. For this to work, the mutant Ab must
      maintain its conformation so that it can be secreted from transfected cells.
      Furthermore, the antigenic peptides must be excised by the processing machinery
      of APC and loaded onto major histo-compatibility complex (MHC) class II
      molecules. To test this, we have introduced a peptide of eleven amino acids
      (a.a.) as either of three different loops in the first C-region domain of the
      heavy (H) chain (CH1) of human IgG3. When the resulting mutant H chain genes were
      expressed in a fibroblast cell line equipped with proper class II molecules, the
      H chains were retained intracellularly, probably due to the light (L) chain
      deficiency of the fibroblasts. Nevertheless, by the endogenous class II
      processing pathway, presentation of the epitope to CD4+ cells was observed for
      all three mutants. The presentation efficiency, however, depended on the position
      of the peptide in the H chain. This could be due to influence of flanking
      sequences, which differ in the three loop replacement mutants. When L chain
      expressing Chinese hamster ovary (CHO) lambda cells were transfected with the
      same constructs, two out of the three mutant Ig were secreted. The mutants had
      the expected antigen specificity and were recognized by anti-IgG Ab. When added
      exogenously to dendritic cell APC, the mutant IgG3 were processed, and the
      liberated foreign epitopes presented to T cells. The results suggest that the
      loops connecting beta-strands in the Ig fold may be replaced by foreign peptides,
      which upon processing become stimulatory to CD4+ T cells. Combined with the well
      known targeting function of antibodies, this principle may be useful for
      construction of a new generation of vaccines.

PMID- 9566765
TI  - Linear and cyclic peptides mimicking the disulfide loops in HIV-2 envelope
      glycoprotein induced antibodies with different specificity.
AB  - The aim of this study was to compare the immunogenicity and antigenicity of
      cyclic and linear peptides that mimic the disulfide loops in HIV-2ROD gp125.
      Based on the hypothetical assignment of intrachain disulfide bonds in HIV-2
      envelope glycoprotein, peptides expected to mimic all 11 disulfide-bonded domains
      were synthesized, oxidized or cysteine-alkylated; they were then purified and
      characterized. Rabbits were immunized with either linear cysteine-alkylated
      peptides (L1-L11) or cyclic oxidized peptides (C1-C11). All peptides except 7L
      elicited antibodies with titers between 10(3) and 5 x 10(6). Anti-peptide C (2,
      3, 4, 7, 8, 9, 11) and anti-peptide L (2, 3, 8, 9, 11) antibodies recognized the
      native HIV-2 gp 125. Moreover, we found that cyclization of the peptides
      significantly increased the level of anti-peptide antibodies reacting with the
      intact antigen protein. Deglycosylation increased the level of protein reactivity
      of anti-peptide antibodies and rendered the epitopes in peptides 5, 6, 10
      accessible, which were masked in the native protein. Peptide 1 induced antibodies
      reacting only with the denatured reduced gp125 HIV-2. In addition, while anti
      peptide L antibodies reacted better with L peptide (called "linear" structural
      specificity), anti-peptide C antibodies reacted similarly with L and C peptides
      (called "broad" structural specificity). Interestingly, the "broad" structural
      specificity of antibodies correlated with reactivity against native gp125.
      Although none of these anti-peptide antisera displayed neutralizing activity
      against HIV-2ROD, these results support the hypothesis that the structural
      restriction of peptides have a major influence upon the generation of more
      specific antibodies for recognizing the intact protein.

PMID- 9566766
TI  - Murine mast cells and monocytes express distinctive sets of CD45 isoforms.
AB  - CD45 isoform expression patterns were examined in various mast and monocyte cell
      populations. The reverse transcription-polymerase chain reaction (RT/PCR) and
      Southern analysis showed these myeloid cells express characteristic sets of CD45
      isoforms. Mast cells produce mRNA for two splice variants, one containing exons
      5, 7 and 8 of the alternatively expressed exons (therefore lacking exons 4 and 6)
      and another containing variable exons 7 and 8. Monocytes express three prominent
      CD45 mRNA species, one which includes exons 5, 7 and 8, another with exons 7 and
      8 and the third containing only exon 8 of the variable exons. These results show
      that there are clear differences within the myeloid lineage sub-populations with
      respect to CD45 exon usage which appear to delineate mast cell and monocyte
      specific patterns.

PMID- 9566767
TI  - The differences between the structural repertoires of VH germ-line gene segments
      of mice and humans: implication for the molecular mechanism of the immune
      response.
AB  - Although human and murine antibodies are similar when considering their
      diversification strategies, they differ in the proportion by which kappa and
      lambda type chains are present in their receptive V, repertoires. It has been
      shown that this difference implies a divergence in the structural repertoire of
      the kappa and lambda genes of these species. Nonetheless, the differences in VH
      have not been systematically studied. In this paper a systematic characterization
      of the VH structural repertoire of mice is made, so that a comparison with the VH
      structural repertoire of humans, described in detail elsewhere, could be properly
      accomplished. Our study shows the structural repertoire of mice to be dominated
      by canonical structure class 1-2 (approximately 60%), while in humans the
      dominant one is class 1-3 (approximately 40%). Analysis of the evolutionary
      relationships between human and mice suggest that this divergence may have a
      functional meaning. The implications of such findings are discussed.

PMID- 9566768
TI  - Structural analysis of an anti-estradiol antibody.
AB  - An anti-estradiol antibody with improved specificity is searched for by combining
      steroid analog binding studies, mutant antibodies obtained from a phage-display
      library and structural modeling. Three-dimensional models for the anti-estradiol
      antibody 57-2 were constructed by comparative model building. Estradiol and
      analogs were docked into the combining site and molecular dynamics simulation was
      used to further refine this area of the protein. Cross-reactivities measured
      against 36 steroid analogs were used to help in the docking process and to
      evaluate the models. The roles of a number of residues were assessed by
      characterization of cross-reactivity mutants obtained from a phage display
      library. The cross-reactivity data and the results observed for mutants are
      explained by the structural model, in which the estradiol D-ring inserts deeply
      into the binding site and interacts with the antibody through at least one
      specific hydrogen bond. The binding data strongly suggest that this hydrogen bond
      connects the estradiol 17-hydroxyl group with the side chain of Gln H35. As
      expected for the binding of a small aromatic molecule, the antibody binding site
      contains many aromatic residues, e.g. Trp H50, H95 and L96 and Tyr L32, L49 and
      Phe L91.

PMID- 9566769
TI  - A mouse molecular mimic of human vascular adhesion protein-1.
AB  - Human vascular adhesion protein-1 (VAP-1) is an endothelial sialoglycoprotein
      which exists in forms of Mr 90000 and 170000 and mediates lymphocyte binding to
      vessels under shear. VAP-1 is functionally defined by an inhibitory mouse mAb
      1B2. A large-scale immunoaffinity purification of VAP-1 from human tonsil lysates
      was performed to determine the protein sequence for VAP-1 cDNA cloning. A
      dominant protein of molecular weight 90000 was obtained which yielded an N
      terminal sequence of 20 amino acids which bore no significant identity to any
      protein sequence in the data banks. A mouse mAb (5B11) against a synthetic
      peptide from this sequence was raised and found to stain tissues in an identical
      manner to mAb 1B2, to inhibit lymphocyte adhesion to endothelial cells and to
      recognize VAP-1. Later, the N-terminal sequence obtained from the 1B2
      immunoprecipitations was found to be identical to a mouse cyclophilin C
      associated protein (mCyCAP) subsequently published by others. We show here by
      several criteria at the protein and DNA level that VAP-1 is distinct from mCyCAP.
      Moreover, we elucidate the mechanism which results in binding of mCyCAP to mAb
      1B2 during antibody synthesis in hybridoma cells and the sequelae of co
      precipitation of mCyCAP during the immunoaffinity chromatography. Binding of
      mCyCAP to a mouse mAb has not been described before and suggests a new function
      for this molecule in immunoglobulin synthesis and/or secretion. Moreover, these
      data indicate that the N-terminal peptide of mCyCAP is a molecular mimic of a
      functionally important epitope of VAP-1.

PMID- 9566770
TI  - LEA-1/ICAM-1 interaction is essentially involved in the pathogenesis of delayed
      type hypersensitivity-induced liver injury to picryl chloride.
AB  - The kinetics of lymphocyte function associated antigen 1 (LFA-1) expression on
      spleen cells (SPC) and liver non-parenchymal cells (NPC), and intercellular
      adhesion molecule 1 (ICAM-1) expression on hepatocytes (HC) was examined in acute
      liver injury mice induced by a DTH reaction to picryl chloride (PCl). The peak
      expression of LFA-1 on SPC was seen at 6 hr after eliciting liver injury, and
      then that of LFA-1 on NPC and ICAM-1 on HC appeared at 12 hr. Thereafter, the
      serum ALT elevation reached to a peak at 18 hr. A splenectomy before the PCl
      elicitation significantly reduced the ALT elevation. Both SPC and NPC from liver
      injury mice induced a remarkable release of ALT from HC in vitro, in parallel
      with their LFA-1 expression. The pre-treatment of NPC or SPC with anti-LFA-1 mAb,
      irrespective of the presence of complement, completely blocked the ALT release.
      Also, when HC was prebound with anti-ICAM-1 mAb, neither NPC nor SPC showed a
      cytotoxicity against the HC. Furthermore, the treatment of NPC with either anti
      Thy1.2 or anti-CD4 mAb in the presence but not absence of complement, showed a
      complete abolishment of ALT release. Anti-CD8 mAb plus complement also tended to
      inhibit ALT release. The twofold increase in CD4+ LFA-1+ and mild increase in
      CD8+ LFA-1+ populations were also confirmed in NPC at 12 hr. These results
      suggest that PCl elicitation in liver may trigger an increased expression of LFA
      1 on SPC and NPC and ICAM-1 on HC. LFA-1/ICAM-1 interaction between liver
      infiltrating NPC, mainly including CD4+ and CD8+ T cells, and HC may be an
      essential step for the hepatocyte damage in PCl-DTH liver injury.

PMID- 9566771
TI  - Alpha interferon administration paradoxically inhibits the development of
      diabetes in BB rats.
AB  - Alpha-interferon (IFN-alpha) is thought to be important in the pathogenesis of
      insulin dependent diabetes mellitus (IDDM). However, since potent inducers of IFN
      alpha, viruses, have been shown to modulate immune function and autoimmunity, we
      investigated whether administration of recombinant IFN-alpha (rIFN-alpha) would
      inhibit the diabetic process in BB rats. The development of diabetes was
      significantly inhibited by injections of either 10(5) units or 4x10(5) units rIFN
      alpha. rIFN-alpha was more effective in preventing disease when injections were
      initiated at an earlier age (28-30 days vs 35-40 days). Histologic examination
      revealed a markedly lower degree of insulitis in rIFN-alpha treated rats. The
      mean total peripheral WBC and differential count, T-cell subsets, peripheral
      blood NK cell number, splenic NK cell activity, and serum cytotoxic beta cell
      surface antibody levels were unaltered by rIFN-alpha administration. In vitro
      incubation with rIFN-alpha inhibited the Con A proliferative response of
      mononuclear splenocytes of BB rats but not of Sprague Dawley rats. These results
      document that rIFN-alpha treatment potently prevents diabetes by inhibiting the
      development of insulitis. This paradoxical diabetes sparing effect may have
      significant implications for the treatment and prevention of IDDM and towards the
      understanding the autoimmune process.

PMID- 9566772
TI  - Evidence supporting a role for ATP as non-adrenergic non-cholinergic inhibitory
      transmitter in the porcine ileum.
AB  - The aim of this study was to investigate the nature of the non-adrenergic non
      cholinergic (NANC) inhibitory transmitter of the circular muscle of the porcine
      ileum. For this purpose, the effects of putative NANC mediators i.e. NO,
      vasoactive intestinal polypeptide (VIP) and ATP were measured in isolated organ
      bath experiments (in basal conditions and after incubation with neostigmine 3 x
      10[-5] M) and using the microelectrode technique. The NO donor sodium
      nitroprusside (NaNP) up to 10(-4) M, VIP up to 10(-7) M and ATP up to 10(-4) M
      failed to cause significant relaxation in the basal state. However, all of them
      induced marked relaxations when the tissue had been preincubated with neostigmine
      (3 x 10[-5] M) which was added to increase basal mechanical activity. The resting
      membrane potential (RMP) was unaffected by NaNP(up to 10(-4) M and VIP up to 10(
      7) M whereas ATP (up to 10[-4] M) induced a transient hyperpolarization. The
      inhibitory junction potentials (IJPs) induced by electrical field stimulation
      (EFS) were not affected by N omega-nitro-L-arginine (L-NNA) (10[-4] M) whereas
      suramin, a purinoceptor antagonist, decreased (10[-4] M) or abolished (10[-3] M)
      the IJPs. Relaxations induced by ATP in neostigmine preincubated tissue were
      resistant to 10(-6) M tetrodotoxin, an axonal blocker, and inhibited by suramin.
      Apamin (10[-6] M, a small conductance calcium activated potassium channel
      blocker, completely abolished the IJP (n=5) and significantly decreased the
      relaxation induced by ATP (n=5). The present data provide support to the
      hypothesis that ATP is the NANC inhibitory transmitter in the porcine ileum
      acting on P2 muscular receptors. Nevertheless, VIP and NaNP do also cause
      relaxation of preparations preincubated with neostigmine.

PMID- 9566773
TI  - The effect of high altitude and caloric restriction on reactive carbonyl
      derivatives and activity of glutamine synthetase in rat brain.
AB  - Both exposure to high altitude (HA) and caloric restriction (CR) may influence
      free radical generation. The aim of the present study was to evaluate the effects
      of 4 wk chronic exposure to 4,000m of HA and CR (60% of CR of control (C) rats)
      on protein oxidation in brain. Eighteen rats with similar body mass were assigned
      to CR, HA and C rats. Reactive carbonyl derivatives (RCD), marker of protein
      oxidation, were measured by Western blot. In addition, the activity and protein
      content of glutamine synthetase (GS) were determined. The body mass of C rats was
      significantly higher (P< 0.001) than that of HA and CR groups. The quantified
      signal intensity of RCD was significantly stronger in C rats than in HA and CR
      rats. The activity of GS was significantly increased in CR rats, while the
      protein content of GS was decreased in HA rats compared to C group. The data
      suggest that both HA and CR decreases the accumulation of RCD in the brain,
      however the mechanism of the decrease seems to be different during HA and CR.

PMID- 9566774
TI  - Plasma and platelet concentration and platelet uptake of serotonin in normal and
      pre-eclamptic pregnancies.
AB  - Pharmacologic and methodologic advances over the last decade have resulted in a
      body of information implicating serotonin as a mediator in the genesis of pre
      eclamptic hypertension. Platelets contain the largest storage of serotonin in
      peripheral blood and have the ability to take up this amine from surroundings,
      store and release it by several mechanisms. Plasma and platelet serotonin
      concentrations and platelet serotonin uptake have been measured in 8 non-pregnant
      women, 12 normal pregnant women and 8 women with severe pre-eclampsia. Plasma
      serotonin concentration was significantly higher in severely preeclamptic women,
      compared with age and gestation matched normal pregnant women. In addition,
      plasma serotonin concentration was directly related to systolic and diastolic
      blood pressure with severity of the syndrome. Furthermore, platelet serotonin
      concentration in women with pre-eclampsia was significantly higher than in non
      pregnant controls, but it was not significantly different from the normal
      pregnant women. Moreover, serotonin is effectively taken up by platelets through
      a saturable transport process. The calculated apparent Km for serotonin uptake
      process did not differ significantly among non-pregnant women, normal pregnant
      women and women with pre-eclampsia. However, Vmax values were significantly
      higher in women with pre-eclampsia than in the normotensive pregnant women. As
      the actions of serotonin in the periphery could be terminated primarily by active
      uptake system by platelets and placenta, significant alterations in the rate of
      transport could result in physiologically significant changes in serotonin
      levels. These data raise the possibility that abnormal regulation of transporter
      function is involved in the etiology of pre-eclampsia.

PMID- 9566775
TI  - Docosahexaenoic acid exhibits a potent protection of small intestine from
      methotrexate-induced damage in mice.
AB  - Oral administration of methotrexate (MTX) to mice causes the damage of small
      intestine. The permeability of poorly absorbable compound fluorescein
      isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) through
      the small intestine was studied in vitro using everted segments of the small
      intestine. The permeability of FITC-dextran increased remarkably in the MTX
      treated mice and oral administration of docosahexaenoic acid ethyl ester (DHA)
      protected the small intestine from the increase in the small intestinal
      permeability induced by the MTX treatment. The MTX treatment decreased retinol
      concentration in plasma of mice and the coadministration of DHA maintained its
      concentration to the level of control mice. The present study showed that DHA
      protected the small intestine of mice from the MTX-induced damage.

PMID- 9566776
TI  - Cigarette smoke extract is a modulator of mitogenic action in vascular smooth
      muscle cells.
AB  - Cigarette smoking is associated with an increased incidence of atherosclerotic
      disease. In this study, we examined the mechanism underlying the growth
      modulating effects of cigarette smoke extract (CSE) in confluent vascular smooth
      muscle cells (VSMCs). The treatment of VSMC by CSE decreased the activities of
      superoxide dismutase (SOD), catalase and glutathione peroxidase of VSMC in a time
      dependent manner. In mitogenesis assays using the confluent cells, CSE was not a
      direct mitogen for VSMC, but potentiated the stimulatory effect of hydrogen
      peroxides. The reduction of activities of catalase and glutathione peroxidase was
      partially prevented by SH-containing compounds. In summary, CSE enhanced the
      mitogenic effect response of hydrogen peroxides, largely depending on the
      dysregulation of the activities of SOD, catalase and glutathione peroxidase by
      CSE.

PMID- 9566777
TI  - Structural determinants of oleoyl-estrone slimming effects.
AB  - Female adult 9-week old Wistar rats were implanted with osmotic minipumps
      releasing for 14 days a liposome suspension (controls) loaded with oleoyl-estrone
      or other compounds of the Merlin series: estrone, estradiol, oleoyl-estradiol,
      oleoyl-DHEA, stearoyl-estrone, palmitoyl-estrone, oleoyl-diethylstilbestrol
      (DES), estrone oleoyl-ether and oleoyl-3-methoxy-estrone. All compounds were
      given at the same dose of 3.5 micromol/day x kg for 14 days. The effects on body
      weight and food intake were recorded. In the case of estrone esters, the body
      composition and nitrogen balance were also determined. The chronic administration
      of oleoyl-estrone in liposomes to rats lowers food intake, maintaining energy
      consumption, thus inducing the active utilization of internal stores and,
      consequently, the loss of body weight. This loss is mainly due to a decrease in
      fat, with lower proportional losses of water and a limited consumption of body
      protein. Free estrone had no effects on body weight, but estradiol did induce a
      decrease in body weight, similar to that of oleoyl-estradiol. Oleoyl-DHEA had no
      significant effect on body weight nor in food intake. Oleoyl-DES mimicked fairly
      well the effects of oleoyl-estrone, both affecting food intake and body weight.
      There was a relative lack of effects of estrone oleoyl-ether and of oleoyl-3
      methoxy-estrone. The effects of oleoyl-estrone were in part mimicked by stearoyl-
      and palmitoyl-estrone, but their activity on a molar basis was lower, which
      suggests that the fatty acid moiety significantly influences the activity of the
      estrone ester as a slimming agent. The differences observed in the appetite
      suppression and overall slimming power of the stearoyl and palmitoyl-estrone
      clearly indicate that the sites of action of the physiological agonist oleoyl
      estrone are at least two; the shape of the molecule, thus, may elicit a different
      degree of response of the systems controlled by oleoyl-estrone levels. From this
      interaction a series of global effects are elicited, such as appetite suppression
      and the loss of body (fat) weight, the latter in part (but not only) due to
      decreased food intake. The results shown here also suggest that the overall
      configuration of fatty acyl-estrone is more constrictive for its function as
      slimming agent than for its role as appetite suppressant, which hints to
      different target organs or sites of action endowed with receptors showing
      different degrees of fulfilling the structural constrictions of the agonist
      molecule.

PMID- 9566778
TI  - The effect of gentamicin on acetylsalicylic acid-induced platelet antiaggregatory
      action in mouse pial arterioles.
AB  - Gentamicin (G) treatment (5, 20, 40 and 80 mg kg[-1] day[-1] given
      intramuscularly for 6 days) was shown to cause a dose-related platelet
      proaggregatory effect in mouse pial microcirculation. This was associated with a
      reduction in mouse renal function, indicated by high plasma creatinine and urea
      concentrations. When G was given at the same doses but as a single injection, it
      caused no change in renal function or platelet aggregation. Gentamicin (20 and 80
      mg kg/day, given intramuscularly for 6 days) significantly (P < 0.05) impeded the
      platelet antiaggregatory effect of acetylsalicylic acid (100 mg kg[-1],
      intraperitoneally).

PMID- 9566779
TI  - Comparison of three different experimental methods for the assessment of
      peripheral compartment pharmacokinetics in humans.
AB  - In many cases the concentration reached in a peripheral effect compartment rather
      than in plasma determines the clinical outcome of therapy. Therefore, several
      experimental approaches have been developed for direct assessment of drug
      kinetics in peripheral compartments. Particularly saliva sampling, skin blister
      fluid sampling, and in vivo microdialysis are frequently employed for measuring
      peripheral drug concentrations. However, data derived from these techniques have
      never been directly compared. In the present study, the tissue kinetics of
      theophylline were measured following single dose administration simultaneously in
      cantharides induced skin blisters, saliva and microdialysates of subcutaneous-
      and skeletal muscle- tissue and compared to plasma concentrations. Theophylline
      was administered to 9 healthy volunteers as an i.v. infusion of 240 mg. Mean
      ratio (AUCsaliva/AUCplasma) was 0.63 +/- 0.05, mean ratio (AUCblister/AUCplasma)
      was 0.69 +/- 0.12, mean ratio (AUCmuscle/AUCplasma) was 0.41 +/- 0.10, mean ratio
      (AUCsubcutaneous/AUCplasma) was 0.34 +/- 0.07. The time course of the
      concentration(peripheral)/concentration(plasma)-ratios showed that tissue
      concentrations obtained by microdialysis were closely correlated to free plasma
      levels, whereas saliva- and cantharides blister data overestimated the
      corresponding free plasma concentrations. It is concluded that microdialysis
      represents a reliable technique for the measurement of unbound peripheral
      compartment concentrations and is superior to saliva- and skin blister
      concentration measurements.

PMID- 9566781
TI  - Fructose-1,6-diphosphate enhanced oxyradicals and nitric oxide-dependent
      suppressions by dexamethasone of ischemic and histamine paw edema of mice.
AB  - Dexamethasone (Dex, 0.1 mg/kg, s.c.) suppressions of ischemic paw edema in mice
      at 1, 3, 6, 8, 18 hr were; 2, 22, 12, 11, 7%. Dex suppression in fructose-1,6
      diphosphate (FDP, 100 mg/kg, i.p.)-treated mice were; 5, 49, 51, 42, 33%.
      Suppressions by this dose of FDP alone were less than 10% during 0-18 hr. ED30 at
      6 hr of Dex +/- FDP was: 80 versus 500 mg/kg in ischemic-, and 5 versus 30 mg/kg
      in histamine edema. Endogenous oxyradicals or NO and protein synthesis were
      essential for suppressions. FDP may not change glucocorticoid receptor (GR)
      conformation, but increase ATP-dependent GR recycling efflux from nucleus. FDP is
      possible to supply this ATP. Clinical trial of FDP with low dose of Dex seems
      advantageous.

PMID- 9566780
TI  - Effect of a nitric oxide-releasing naproxen derivative on hypertension and
      gastric damage induced by chronic nitric oxide inhibition in the rat.
AB  - NSAIDs can elevate blood pressure through mechanisms such as renal
      vasoconstriction and sodium retention. These effects are particularly evident in
      hypertensive individuals. Nitric oxide-releasing NSAID derivatives have been
      shown to have greatly reduced toxicity in the gastrointestinal tract and kidney.
      We therefore evaluated the effects of a 4 week treatment with either naproxen or
      its nitric oxide-releasing derivative (NO-naproxen) on systemic arterial blood
      pressure and gastric damage in rats in which hypertension was induced by L-NAME.
      Rats received either L-NAME dissolved in the drinking water (400 mg/L) or tap
      water (control). Vehicle, naproxen (10 mg/kg) or an equimolar dose of NO-naproxen
      (14.5 mg/kg) were administered orally each day. After 4 weeks, blood pressure was
      measured, blood samples were taken for measurement of thromboxane synthesis, and
      gastric damage was evaluated by blind, macroscopic scoring. Both naproxen and NO
      naproxen inhibited systemic cyclooxygenase activity by >90%. NO-naproxen-treated
      rats exhibited no significant gastric damage. The gastric damage produced by L
      NAME alone was potentiated by naproxen but prevented by NO-naproxen. L-NAME
      treatment significantly increased blood pressure. In the absence of L-NAME, the
      naproxen group had significantly higher blood pressure than both the control and
      NO-naproxen groups. In rats receiving L-NAME, the same conclusions apply, but the
      concomitant administration of NO-naproxen was able to significantly reduce the
      blood pressure compared to L-NAME alone. Based on these results, we conclude that
      NO-naproxen may represent a safer alternative to standard NSAIDs in the treatment
      of inflammatory conditions in hypertensive patients.

PMID- 9566782
TI  - Selective CD8+ T cells accumulate in the lungs of patients with allergic asthma
      after allergen bronchoprovocation.
AB  - Our objective was to study whether CD4+ or CD8+ T cells expressing particular T
      cell receptors (TCR) would accumulate in the lungs of patients with allergic
      asthma following allergen exposure. We thus analysed the TCR Valpha and Vbeta
      gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBL) of eight
      patients with allergic asthma before and 4 days after inhalation challenge with
      the relevant allergen. Lung cells obtained by bronchoalveolar lavage (BAL) and
      paired PBL samples were analysed by flow cytometry using a panel of anti-TCR V
      specific monoclonal antibodies that encompass = 50% of the T cell repertoire.
      Lung-limited T cell expansions were recorded in both the CD4+ and the CD8+
      subsets. In BAL CD8+, out of a total of 126 analyses, the number of T cell
      expansions increased from two to 11 after challenge, some of them dramatic. In
      BAL CD4+ the frequency of expansions was moderately increased already before
      challenge, but remained unchanged. A few expansions that tended to persist were
      noted in PBL CD8+. When analysing the overall change in TCR V gene usage the
      largest changes were also recorded in the BAL CD8+ subset. Specific interactions
      between T cells and antigens may lead to an increased frequency of T cells using
      selected TCR V gene segments. In this study we demonstrate that following
      allergen bronchoprovocation in allergic asthmatic subjects, T cell expansions
      preferentially emerge in the lung CD8+ T cell subset.

PMID- 9566783
TI  - Catalase and alpha-enolase: two novel granulocyte autoantigens in inflammatory
      bowel disease (IBD).
AB  - In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA)
      have not been fully identified, which limits the analysis of the diagnostic
      significance as well as of the possible pathophysiological role of these
      antibodies. In this study, we identify the target antigens of ANCA in large
      groups of patients with ulcerative colitis (UC) and Crohn's disease (CD). Apart
      from antibodies against lactoferrin and bactericidal/permeability-increasing
      protein (BPI), which have been reported before, antibodies against two novel
      granulocyte antigens were identified: antibodies against a 57/56-kD doublet were
      found in 38% of samples from UC patients and in 26% of samples from CD patients,
      whereas antibodies against a 47-kD protein were found in 10% of samples from UC
      patients and in 18% of samples from CD patients. Partial purification and amino
      acid sequence analysis identified the 57-kD protein as catalase and the 47-kD
      protein as alpha-enolase. This study is the first to report catalase and alpha
      enolase as granulocyte antigens for autoantibodies in IBD.

PMID- 9566784
TI  - Epitopes expressed in myasthenia gravis (MG) thymomas are not recognized by
      patients' T cells or autoantibodies.
AB  - Most thymic epithelial tumours that associate with MG express an epitope that
      resembles the sequence alpha373-380 from the cytoplasmic loop of the
      acetylcholine receptor (AChR). It has been proposed that sensitization to this
      linear epitope initiates autoimmunity to the AChR in thymoma-associated MG. We
      therefore tested whether MG/thymoma patients have T cell responses or antibodies
      to this region of the AChR. We found no significant recognition of the alpha309
      417 region by their thymoma or peripheral blood T cells, or by their serum anti
      AChR antibodies. Instead, the T cell epitopes that were recognized, like the
      previously characterized B cell epitopes, were in the extracellular AChR domain.

PMID- 9566785
TI  - Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+CD18+
      cells and CD8+CD103+ cells by multi-epitope imaging.
AB  - Pancreatic cancer is characterized by an increasing incidence and an extremely
      poor prognosis. It is resistant to most of the conventional treatment modalities.
      Histomorphologically, it presents with a strong desmoplastic reaction around
      cancer cells, and lymphocytes are typically localized as aggregates in the
      fibrotic interstitial tissue. Using the method of multi-epitope imaging with
      fluorochrome-tagged specific MoAbs which allows the simultaneous localization and
      characterization of T cells in tissues, we studied phenotypes and distribution of
      tumour-infiltrating lymphocytes (TIL) in pancreatic cancer. CD3+ T cells
      comprised up to 90% of the tumour-infiltrating cells which were either CD4+ or
      CD8+, most of them being memory cells (CD45RO+). In decreasing order of
      frequency, T lymphocytes carried the markers for CD45RO, CD18, CD103 and TCR
      gammadelta. Very few natural killer cells (CD56+) were observed. Twenty percent
      of CD8+ were labelled with CD103. These CD8+CD103+ T cells, analogous to the gut
      intraepithelial lymphocytes (IEL), were found in the fibrous interstitial tissue.
      Furthermore, an inverse correlation was found between the expression of CD18, the
      beta2-integrin, which mediates adhesion of activated lymphocytes, and CD45RO in
      the CD8+ subset of TIL (P = 0.046). In conclusion, phenotyping of T lymphocytes
      in pancreatic cancer raises the possibility that pancreatic cancer cells develop
      several strategies to escape the T cell-induced cytolysis by (i) the aggregation
      of cytotoxic CD8+CD103+ T cells in the fibrous tissue distant from the tumour
      cells, and (ii) the presence of CD18-bearing cells which lack the expression of
      the activation marker CD45RO.

PMID- 9566786
TI  - Mapping epitopes for 20 monoclonal antibodies to CR1.
AB  - Complement receptor type one (CR1; CD35) binds and processes C3b and C4b
      opsonized immune complexes and regulates complement activation. We have
      characterized the epitopes of 13 previously reported and seven new MoAbs to human
      CR1. The MoAbs formed seven groups based on their reactivity with a panel of
      deletion forms of CR1. Seventeen of the MoAbs reacted with CR1 at more than one
      site, a consequence of its repetitive sequence. All five of the MoAbs recognizing
      epitopes in the nearly identical repeats 3, 10, and 17, as well as one MoAb which
      reacted with repeats 8 or 1/2 of 9 and 15 or 1/2 of 16, blocked cofactor activity
      for C3b. Knowledge of the repeats bearing the epitopes for these MoAbs should
      facilitate the further characterization of CR1.

PMID- 9566787
TI  - Polarized secretion of IL-6 and IL-8 by human retinal pigment epithelial cells.
AB  - A number of cell types situated along interfaces of various tissues and organs
      such as the peritoneum and the intestine have been shown to secrete inflammatory
      cytokines in a polarized fashion. Retinal pigment epithelial (RPE) cells are
      positioned at the interface between the vascularized choroid and the avascular
      retina, forming part of the blood-retina barrier. These cells are potent
      producers of inflammatory cytokines and are therefore considered to play an
      important role in the pathogenesis of ocular inflammation. Whether cytokine
      secretion by these cells also follows a vectorial pattern is not yet known, and
      was therefore the subject of this study. Monolayers of human RPE cells (primary
      cultures and the ARPE-19 cell line) cultured on transwell filters were stimulated
      to produce IL-6 and IL-8 by adding IL-1beta (100 U/ml) to either the upper or the
      lower compartment. After stimulation, the human RPE cell lines showed polarized
      secretion of IL-6 and IL-8 towards the basal side, irrespective of the side of
      stimulation. The ARPE- 19 cell line also secreted IL-6 and IL-8 in a polarized
      fashion towards the basal side after basal stimulation; polarized secretion was,
      however, not apparent after apical stimulation. The observation that human RPE
      cells secrete IL-6 and IL-8 in a polarized fashion towards the choroid may
      represent a mechanism to prevent damage to the adjacent fragile retinal tissue.

PMID- 9566788
TI  - Characterization of the CDR3 region of rearranged alpha heavy chain genes in
      human fetal liver.
AB  - The human fetal liver is an early site for B cell development. Pre B cells are
      first detectable in human fetal life at 8 weeks of gestation, when the
      rearrangement of the mu heavy chain genes starts. In this study we characterize
      the CDR3 region of rearranged alpha heavy chain transcripts from four human fetal
      livers ranging from 8 to 11 weeks of gestation. Each fetal liver showed a limited
      number of variations in CDR3 sequences compared with adult peripheral blood
      mononuclear cells (PBMC). Sequence analysis of 91 clones demonstrated that there
      was no preference for the usage of a certain JH gene segment, whereas a
      preference for usage of DH family genes, DXP and DLR, was seen in most cases
      during early fetal life. This is the first study where rearranged alpha heavy
      chain genes in fetal liver have been characterized. Our data suggest that the
      usage of JH genes is random, while there is a preference for DH family genes in
      human fetal liver.

PMID- 9566789
TI  - Progressive decrease of CD8high+ CD28+ CD57- cells with ageing.
AB  - An age-dependent decrease in T cell responsiveness to CD28 costimulation has been
      described. In order to test the hypothesis that an age-related decrease in CD28
      expression by CD8+ T lymphocytes might be involved, we analysed 67 healthy donors
      ranging in age from 15 to 69 years for their CD8+ T cell expression of CD28 and
      CD57. We found a statistically significant decrease of CD28 expression through
      ageing and a significant increase of CD57 expression, both markers being mutually
      exclusive. Given that cytomegalovirus (CMV) is reported to induce CD57
      expression, and since the carrier status for this ubiquitous virus increases with
      age in the general population, it seemed essential to evaluate whether the
      phenotypic age-related changes described in CD8high+ cells were not influenced by
      the CMV carrier status of the individuals. Accordingly, we performed a
      multivariate analysis to assess the independent association of age and CMV
      carrier status with CD28 and CD57 expression in CD8high+ cells. Results showed
      that the progressive decrease in CD8high+ CD28+ CD57- cells was associated only
      with age, while the expansion of the CD8high+ CD28- CD57+ subset depended both on
      age and CMV, although mainly on age. We conclude that ageing is accompanied by a
      progressive loss of CD28 expression in CD8+ T cells and a reciprocal enhancement
      of CD57 expression, both facts being probably related to the repeated antigenic
      stimulation occurring throughout life.

PMID- 9566790
TI  - Gammadelta+ and CD4+ alphabeta+ human T cell subset responses upon stimulation
      with various Mycobacterium tuberculosis soluble extracts.
AB  - By using a flow cytometric technique which allows direct identification of
      proliferating cells within mixed cell populations, we have previously described
      that soluble extracts obtained from Mycobacterium tuberculosis or M. avium
      represent strong stimuli for human gammadelta+ T cells. In the present study, we
      demonstrate that the protocol used for the preparation of M. tuberculosis soluble
      extracts may have an impact on their gammadelta+ T cell stimulatory capacity. In
      agreement with our previous data, soluble extracts prepared from bacteria killed
      at 85 degrees C and directly disrupted by prolonged sonication (TBe), elicited a
      strong proliferation of gammadelta+ T cells after 6-7 days of stimulation. In
      contrast, when soluble extracts were obtained from bacteria autoclaved (121
      degrees C, 25 min) and then washed by centrifugation, a predominant proportion of
      CD4+ alphabeta+ T cells was achieved in the responding population. The
      stimulatory activity for gammadelta+ T cells was recovered in the supernatant of
      the autoclaved bacteria, indicating that autoclaving of M. tuberculosis bacilli
      releases an antigen(s) into the supernatant which stimulates human gammadelta+ T
      cells. While protease digestion of TBe only partially reduced its stimulatory
      capacity on gammadelta+ T cells, the stimulatory component(s) released into the
      supernatant after autoclavation of bacilli was found to be sensitive to protease
      digestion. Interestingly, in contrast to the preponderant proportion of
      gammadelta+ T cells induced in the responding population by unfractionated TBe,
      when the extract was fractionated by fast performance liquid chromatography
      (FPLC), most of the fractions exhibited a strong stimulatory capacity on CD4+
      alphabeta+ T cells only. The gammadelta+ T cell stimulatory activity was confined
      to the low molecular weight range FPLC fractions. Such results may suggest a
      possible regulatory role of gammadelta+ T cells on CD4+ alphabeta+ T cells.

PMID- 9566791
TI  - Differential potentiation of anti-mycobacterial activity and reactive nitrogen
      intermediate-producing ability of murine peritoneal macrophages activated by
      interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha).
AB  - The anti-mycobacterial activities of IFN-gamma and TNF-alpha-treated murine
      peritoneal macrophages were determined. Resident macrophages pretreated with IFN
      gamma or TNF-alpha for 2 days were infected with test organisms and subsequently
      cultured for up to 7 days. First, the early-phase growth of Mycobacterium
      tuberculosis (days 0-3) was strongly suppressed in IFN-gamma-treated macrophages,
      and progressive bacterial elimination was subsequently observed. Although TNF
      alpha treatment of macrophages did not affect the early phase growth of
      organisms, bacterial killing was observed in the later phase of cultivation.
      Second, although IFN-gamma-treated macrophages killed M. avium during the first 3
      days of culture, regrowth of the intracellular organisms was subsequently
      observed. TNF-alpha treatment of macrophages did not influence the mode of
      intracellular growth of M. avium. Third, IFN-gamma but not TNF-alpha enhanced
      production of reactive nitrogen intermediates (RNI) by macrophages infected with
      M. tuberculosis or M. avium, whereas both cytokines increased macrophage release
      of reactive oxygen intermediates (ROI). The present findings therefore show that
      IFN-gamma and TNF-alpha potentiated the anti-mycobacterial activity of murine
      peritoneal macrophages in different fashions. They also suggest that RNI played
      more important roles than did ROI in the expression of macrophage anti
      mycobacterial, particularly anti-M. avium, activity.

PMID- 9566792
TI  - Differential antigen-stimulated proliferation of human mononuclear cells by
      recombinant Schistosoma japonicum antigens in a Chinese population.
AB  - Peripheral blood mononuclear cells (PBMC) from 117 individuals living on two
      islands in an area (Dongting Lake) endemic for schistosomiasis japonica in China,
      and 15 control individuals from a non-endemic area of China, were assessed for
      antigen-stimulated proliferation against five recombinant Schistosoma japonicum
      antigens of recognized interest in the development of immunity to
      schistosomiasis. Two recombinant antigens, paramyosin and 28-kD glutathione-S
      transferase, stimulated cellular proliferation (stimulation index > or = 3.0) in
      38.5% and 42.5% of subjects, respectively, a level similar to that induced by a
      soluble whole parasite extract (51.3%). In contrast, three other recombinant
      antigens tested--a fatty acid binding protein, 22-kD tegumental membrane
      associated antigen, and glyceraldehyde-3-phosphate dehydrogenase--stimulated PBMC
      proliferation in only 3-8% of subjects. Moreover, we also identified a positive
      association between the degree of exposure, and cellular proliferation following
      stimulation with recombinant paramyosin or whole parasite extract. Highly
      significant differences in antigen-stimulated proliferation were also observed
      between the two islands, Niangashan and Qingshan. The whole parasite extract
      stimulated proliferation in 90% of subjects from Niangashan island compared with
      only 42.1% of subjects from Qingshan island (chi2 = 16.88, P = 0.00004), while
      glutathione-S-transferase stimulated proliferation in 77.3% of subjects from
      Niangashan island compared with only 34.7% of subjects from Qingshan island (chi2
      = 13.09, P = 0.003). A similar, but not significant, trend was observed for
      paramyosin and the fatty-acid binding protein. The identification of differential
      cellular proliferative responses to specific schistosome antigens within an
      infected human population may have important practical implications for vaccine
      development against schistosomiasis japonica.

PMID- 9566793
TI  - Transforming growth factor-beta 1 (TGF-beta1) expression in ovine lentivirus
      induced lymphoid interstitial pneumonia.
AB  - The aim of this study was to detect the localization of TGF-beta1 protein
      expression in normal sheep lungs and lungs with interstitial pneumonia associated
      with infection with maedi-visna virus (MVV). Immunohistochemical localization of
      TGF-beta1 was determined in 24 lungs of adult sheep naturally infected with MVV
      and six control lungs of seronegative sheep. The lungs of infected animals showed
      different lesional degrees: grade 0, no lesions; grade I, mild; grade II,
      moderate; grade III, severe. In normal lungs, TGF-beta1 was primarily expressed
      in airway epithelium, bronchial cartilage and glands, endothelial cells and
      smooth muscle of blood vessels, alveolar macrophages and type II pneumocytes. No
      staining was observed in alveolar interstitium. In MVV-infected sheep an
      increased number of positive alveolar and interstitial macrophages and staining
      of alveolar interstitium was observed in grade I, grade II and some grade III
      lesions. In grade III lesions an inverse relationship was found between TGF-beta1
      staining and smooth muscle hyperplasia. Small lymphoid aggregates, in general,
      showed strong reactivity, whereas larger ones showed weak reactivity, mainly
      associated with follicular areas. No significant differences in the staining
      intensity of airways and blood vessels were observed between control and MVV
      lungs. The increased expression of TGF-beta1 in early maedi lesions and its down
      regulation in more advanced disease suggest the operation of a temporal
      regulatory mechanism whereby early expression may lead to the smooth muscle
      hyperplasia which develops during the disease. The striking inverse relationship
      between TGF-beta1 expression and follicle organization is intriguing and warrants
      further investigation.

PMID- 9566795
TI  - Expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES
      genes in lymph nodes from HIV+ individuals: correlation with a Th1-type cytokine
      response.
AB  - The in vivo response of the immune system after HIV infection in regard to
      cytokine production and C-C chemokine synthesis is not well known. Here we have
      analysed cytokine and chemokine mRNA production in lymph nodes with follicular
      hyperplasia (FHLN) of HIV-infected patients by in situ hybridization using anti
      sense mRNA probes. The synthesis of mRNAs for interferon-gamma (IFN-gamma), IL
      12p35, IL-12p40, IL-4, and for the C-C chemokines RANTES, MIP-1alpha, and MIP
      1beta was compared with that of lymph nodes from non-infected individuals to
      define HIV-specific events. Only few cells expressing IFN-gamma, RANTES, MIP
      1alpha, and MIP-1beta mRNAs were detectable in the T-dependent area of lymph
      nodes from HIV-negatives. In contrast, in FHLN from HIV+ patients a high number
      of IFN-gamma, RANTES, MIP-1alpha, and MIP-1beta mRNA-containing cells were
      detectable. Remarkably, only single individual IL-12p35 mRNA-producing cells were
      present in the T-dependent area from both HIV+ and HIV lymph nodes. Furthermore,
      the low number of IL-12p40 mRNA-expressing cells did not differ between HIV+ and
      HIV- lymph nodes. This indicates that IFN-gamma is expressed independently of IL
      12, possibly by a direct T cell-mediated reaction. IL-4 mRNA-producing cells were
      hardly detectable in infected and control lymph nodes. The same findings were
      made in a limited number of samples from patients with advanced disease. Thus,
      these results demonstrate that a high IFN-gamma production is accompanied by a
      strong expression of MIP-1alpha, MIP-1beta, and RANTES in the lymph node after
      HIV infection. This favours the idea that a Th1-type immune response correlates
      with a preferential production of C-C chemokines in FHLN of HIV+ patients.

PMID- 9566796
TI  - Changes to the cytokine microenvironment in the genital tract mucosa of HIV+
      women.
AB  - As previous studies have indicated that genital tract mucosal T cell function may
      be impaired in HIV infection, we investigated the T cell cytokine mRNA in the
      genital tract mucosa of HIV-infected women to determine if there are alterations
      in the cytokine profile which may explain the T cell impairment. The in situ
      hybridization technique was used to investigate the T helper-1 (Th1: IL-2,
      interferon-gamma (IFN-gamma)) and Th2 cytokine (IL-4, IL-5, IL-10) mRNA profile
      in cervical biopsies from 10 HIV+ and 10 HIV- subjects. Cervical intraepithelial
      neoplasia (CIN) and genital infection had previously been excluded and the
      distribution of immunocompetent cells within the cervical mucosa was known for
      each subject. Non-parametric tests were used to compare the optical density (OD)
      of cytokine mRNA in the HIV+ and HIV- groups. Comparisons were also made between
      peripheral CD4 lymphocyte counts, cervical CD4/CD8 T lymphocyte ratios and
      cytokine mRNA OD in HIV+ subjects. The HIV+ women had significantly higher mRNA
      OD for the Th2 cytokines IL-4, IL-5 and IL-10 than HIV women. There was also
      significantly lower IL-2 mRNA OD in the former group. HIV+ women had lower IFN
      gamma mRNA than HIV- women, but the difference was not statistically significant.
      There was no correlation between cytokine mRNA OD and peripheral CD4 count or
      cervical CD4/CD8 ratio. The predominance of Th2 cytokines, which are immuno
      inhibitory, in the cervical mucosa of HIV+ women may underlie the impaired
      cytotoxic potential observed in the CD8+ T lymphocytes and may contribute to the
      susceptibility of HIV-infected women to recurrent genital tract infections and
      cervical neoplasia.

PMID- 9566794
TI  - Recombinant human IL-16 inhibits HIV-1 replication and protects against
      activation-induced cell death (AICD).
AB  - The chemoattractant cytokine IL- 16 has been reported to suppress lymphocyte
      activation and to inhibit HIV-1 replication in acutely infected T cells. We have
      cloned and expressed human IL-16 in Escherichia coli and investigated whether the
      recombinant protein could regulate the level of lymphocyte apoptosis from HIV-1
      infected subjects. After purification and refolding, only 2-10% of the
      recombinant cytokine was present in a biologically active homotetrameric form.
      This could explain the need for high concentrations of the bacterially derived IL
      16 to induce significant inhibition of HIV-1 replication. Addition of IL-16 to
      unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-1
      infected subjects did not modify the observed level of spontaneous lymphocyte
      apoptosis. In contrast, IL-16 added to PBMC cultures stimulated with anti-CD3,
      anti-CD95 or dexamethasone reduced significantly the percentage of lymphocytes
      undergoing AICD. This effect was found to correlate with the ability of the
      cytokine to decrease CD95 expression on activated CD4+ T cells. Comparative
      studies on PBMC from healthy individuals indicated that the regulation of
      apoptosis levels by IL-16 is a complex phenomenon and could depend on the nature
      of the activator used and/or the immune status of lymphocytes tested. The outcome
      of CD4 cross-linking on T cells by various ligands is discussed in the context of
      the observed beneficial activities of IL- 16 and its potential role in the
      treatment of HIV disease.

PMID- 9566797
TI  - HIV-1 does not alter in vitro and in vivo IL-10 production by human monocytes and
      macrophages.
AB  - The present study analyses the ability of HIV-1 to modulate IL-10 production in
      cells of monocyte-macrophage lineage cultured in the presence of macrophage
      colony-stimulating factor (M-CSF). Both monocytes and macrophages spontaneously
      produced low amount of IL-10. Lipopolysaccharide (LPS) induced a strong IL-10
      response in fresh monocytes and in M-CSF-treated macrophages. In contrast,
      macrophages cultured in the absence of M-CSF exhibited a marked decrease in their
      susceptibility to LPS stimulation. M-CSF increased the IL-10 response of
      macrophages to LPS by enhancing both the expression of membrane-bound CD14, the
      protein that serves as LPS receptor, and the sensibility of CD14-expressing cells
      to LPS stimulation. Neither spontaneous nor LPS-induced expression of IL-10 was
      modulated in monocytes and macrophages by infection with eight monocytotropic
      strains, as demonstrated by ELISA and cytofluorimetric analysis. In contrast, all
      the HIV-1 strains primed macrophages for an increased IL-6 response to LPS
      stimulation. To determine whether IL-10 production was associated with in vivo
      infection, monocytes from AIDS individuals were analysed for IL-10 production. We
      found that neither spontaneous nor LPS-induced IL-10 production were different
      between healthy controls and HIV-infected patients. Taken together, these data
      strongly suggest that HIV-1 infection of monocytes-macrophages does not play a
      significant role in the regulation of IL-10 in infected patients. This study also
      emphasizes the role of M-CSF activation in the regulation of the cytokine
      response in macrophages.

PMID- 9566798
TI  - The effect of cyclosporin A, FK506 and rapamycin on the murine contact
      sensitivity reaction.
AB  - We have evaluated the effects of three potent immunosuppressive agents,
      cyclosporin A (CsA), FK506 and rapamycin, on the murine contact sensitivity (CS)
      reaction to the hapten trinitrochlorobenzene. Development of CS reaction requires
      participation of three distinct T cell subsets: alphabeta+, CD4+ T lymphocytes,
      which are the classical effector cell of the CS reaction, gammadelta+ T
      lymphocytes, and alphabeta+, double-negative (CD4- CD8-) T lymphocytes that
      express the B220 molecule and produce IL-4. We found that all three drugs inhibit
      the development of the CS reaction, but they affect different target cells. In
      fact, rapamycin and FK-506 block both alphabeta+, CD4+ and gammadelta+ T
      lymphocytes, while CsA inhibits only the alphabeta+, CD4+ T lymphocyte. None of
      the three drugs exerted any inhibitory activity on the alphabeta+, double
      negative (CD4- CD8-) T lymphocytes. Hapten-immune lymph node cells from mice
      treated in vivo with CsA or FK506 failed to proliferate and to produce IL-2 when
      re-exposed to the specific antigen in vitro. In contrast, immune lymph node cells
      from mice that had been treated in vivo with rapamycin gave optimal antigen
      specific proliferation and IL-2 production in vitro. The implications of these
      observations are discussed in relation to the use of these immunosuppressive
      agents for prevention of allograft rejection.

PMID- 9566799
TI  - Up-regulation of Fas ligand (FasL) mRNA expression in peripheral blood
      mononuclear cells (PBMC) after major surgery.
AB  - FasL, which is expressed mainly on activated lymphocytes, can induce apoptosis
      (programmed cell death) of cells which express Fas. Fas/FasL interaction is
      primarily beneficial in maintaining immunological and physiological homeostasis
      by eliminating unnecessary cells. Dysregulation of the interaction, however,
      leads to tissue damage. We investigated how Fas/FasL levels changed after major
      surgery. The major aim of this study was to elucidate the involvement of the
      Fas/FasL system in postoperative inflammation. The investigation involved 10
      patients admitted to the intensive care unit after surgery. Although the
      percentage of Fas+ cells and the amount of Fas expression tended to increase,
      there was no significant difference between pre- and post-operative samples. In
      contrast, the levels of FasL mRNA were dramatically up-regulated after operation.
      Post-operative C-reactive protein (CRP) levels increased and correlated well with
      FasL levels (r=0.91, P<0.01). Lymphocyte counts decreased after operation and
      were inversely proportional to FasL levels (r=0.58, P < 0.05). These results
      suggest that the enhanced FasL expression is likely to be related to systemic
      inflammatory responses induced during the perioperative period. FasL up
      regulation may be involved in the aggravation of tissue damage, including
      lymphocytopenia, in the early post-operative period.

PMID- 9566800
TI  - Suppression of IL-6 biological activities by activin A and implications for
      inflammatory arthropathies.
AB  - Activin A is a cytokine whose multiple functions have yet to be fully determined.
      In this study, the role of proinflammatory cytokines in regulatory control of
      activin A production was shown in synoviocytes and chondrocytes. Additional
      facets of functional inflammation-related activities of activin A were also
      determined. Results showed that activin A concentrations in the synovial fluid of
      patients with rheumatoid arthritis and gout were elevated relative to those in
      patients with osteoarthritis. Further studies showed that production of activin A
      by synoviocytes and chondrocytes in culture was stimulated by cytokines such as
      IL-1, transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma),
      and IL-8, consistent with previous studies in regard to the control of activin A
      production in marrow stromal cells and monocytes by cytokines, glucocorticoids
      and retinoic acid. In addition, the relationship of activin A to IL-6-induced
      biological activities was investigated. Three major IL-6 activities involved in
      inflammatory responses were found to be suppressed by activin A. In a dose
      dependent manner, activin A efficiently suppressed IL-6-induced proliferation of
      7TD1 B lymphoid cells, phagocytic activity of monocytic M1 cells, and fibrinogen
      production in HepG2. Therefore, it is likely that activin A serves as a
      suppressor for IL-6, dampening inflammatory responses, and has the potential to
      perform some previously unrecognized roles in inflammation.

PMID- 9566802
TI  - Anti-ribosomal antibodies bind the Sm proteins D and B/B'.
AB  - In order to analyse the specificity of human anti-ribosomal P protein antibodies,
      anti-ribosomal P protein antibodies were affinity-purified from the sera of lupus
      patients. Their binding capacity towards recombinant SmD protein and recombinant
      SmB/B' protein was evaluated by immunoblot and ELISA. Epitope mapping of SmD was
      performed by means of synthetic peptides. Anti-ribosomal P protein antibodies
      bound recombinant SmD (5/10) and SmB/B' (4/10) on immunoblot; 6/10 showed binding
      capacity to SmD on ELISA. Inhibition experiments using ELISA confirmed the
      specificity of this binding. Our data indicate the cross-reactivity of
      spontaneously developed anti-ribosomal P protein antibodies with the B/B' and D
      constituents of the Sm complex. The coexistence of anti-Sm and anti-ribosomal
      antibodies in lupus sera may therefore be due, at least in part, to the
      reactivity of a single autoantibody population.

PMID- 9566801
TI  - Differential inhibitory effects of indomethacin, dexamethasone, and interferon
      gamma (IFN-gamma) on IL-11 production by rheumatoid synovial cells.
AB  - IL-11, a member of the IL-6 type cytokines, has some biological activity related
      to the joint destruction in rheumatoid arthritis (RA), such as induction of
      osteoclast differentiation. However, its expression and regulation in rheumatoid
      inflamed joints has not been clarified. In the present study we examined the
      capacity of fresh rheumatoid synovial cells (fresh RSC) to produce IL-11, and the
      effect of indomethacin, dexamethasone and IFN-gamma on IL-11 production. Fresh
      RSC obtained from eight patients with RA produced large amounts of IL-11,
      measured by ELISA, and showed strong expression of IL-11 mRNA, determined by
      Northern blotting. Indomethacin inhibited the production of IL-11 by about 55%.
      Prostaglandin E2 (PGE2) completely prevented the inhibition, suggesting that IL
      11 production by fresh RSC was in part mediated by PGE2. Dexamethasone inhibited
      the production of IL-11 by more than 80%. Interestingly, the inhibition was not
      abolished by PGE2. IFN-gamma inhibited the production of IL-11 from IL-1alpha
      stimulated cultured rheumatoid synovial fibroblasts, although IFN-gamma did not
      inhibit the production of IL-11 by fresh RSC. These results suggest that the
      production of IL-11 by rheumatoid synovia was differentially regulated by PGE2
      and IFN-gamma, and that treatment with indomethacin or dexamethasone decreased
      the level of IL-11 at inflammatory joints in patients with RA.

PMID- 9566803
TI  - Anti-mitochondrial M5 type antibody represents one of the serological markers for
      anti-phospholipid syndrome distinct from anti-cardiolipin and anti-beta2
      glycoprotein I antibodies.
AB  - The aim of this study was to characterize the antigen specificity and to evaluate
      the diagnostic and prognostic value of anti-mitochondrial M5 type antibodies (AMA
      M5). Fifty-eight patients selected on the basis of their AMA M5 positivity were
      investigated in relationship to their clinical and serological profile. Cross
      absorption studies, Western blotting and immunoprecipitation analysis were
      carried out for AMA M5 antigen specificity characterization. Most patients had a
      diagnosis of systemic lupus erythematosus (SLE) (65.5%) or of primary anti
      phospholipid syndrome (PAPS) (24%); all the patients were positive for IgG or IgM
      anti-cardiolipin (anti-CL) antibodies and 49% of them also displayed lupus
      anticoagulant (LA) activity. Anti-beta2-glycoprotein I (beta2-GPI) IgG were
      detectable in 30/38 sera (78.9%) and IgM in 34/38 (89.4%). While anti-CL and anti
      beta2-GPI IgG antibodies were significantly associated with history of thrombosis
      and fetal loss, AMA M5 displayed a statistical association only for
      thrombocytopenia and recurrent fetal loss. Absorption with human beta2-GPI both
      in free solution or in solid phase as well as with CL liposomes or CL/beta2-GPI
      liposome complexes did not affect AMA M5 fluorescence. While AMA M5 activity is
      absorbed by whole mitochondrial preparations, no specific reactivities against
      several human, bovine and rat mitochondrial proteins could be detected in Western
      blotting and immunoprecipitation studies. AMA M5 appear to be detectable in both
      primary and secondary APS, displaying a strong association with the presence of
      thrombocytopenia and fetal loss. Although strictly related to anti-phospholipid
      antibodies, AMA M5, anti-CL and anti-beta2-GPI antibodies represent distinct
      serological markers of the APS.

PMID- 9566804
TI  - The value of synthetic linear epitope analogues of La/SSB for the detection of
      autoantibodies to La/SSB; specificity, sensitivity and comparison of methods.
AB  - In a previous study it was shown that La/SSB contains four linear epitopes, p147
      154, p291-302, p301-318 and p349-364. The aim of the present study was to
      investigate the value of the synthetic epitope analogues of the La/SSB
      autoantigen for the detection of antibodies to La/SSB, in comparison with
      recombinant La and fragments of this protein. A total of 122 sera with anti
      La/SSB activity, from patients with primary Sjogren's syndrome (pSS) or systemic
      lupus erythematosus (SLE), were tested in various peptide-based assays. In
      addition, 62 sera from pSS or SLE patients with other autoantibody specificities
      and 95 sera from healthy individuals were used as controls. The autoantibody
      specificity was identified by counter immunoelectrophoresis and immunoblot. The
      peptide-based ELISA assays presented sensitivities ranging from 78% to 88-8% and
      specificities from 69% to 94-3%. Dot blot assays exhibited sensitivities ranging
      from 93-6% to 97%, but remarkably lower specificities from 56% to 88%. The most
      sensitive and specific peptide 349GSGKGKVQFQGKKTKF364 was synthesized and
      attached on a tetramer sequential oligopeptide carrier SOC4 and used for
      immunoassay development. Assays based on the recombinant native La protein, the
      La-C terminal (215 aa), and the N-terminal of La with a mutation at base pair 640
      (nine adenines instead of eight) were also developed and compared with the SOC4
      peptide-based assay. Of anti-La-positive sera, 88.1% were reactive with both the
      synthetic peptide SOC4-(349-364aa) and the recombinant La protein. Eighty-three
      percent of sera were reactive with the La N-terminus and 67.8% of sera were
      reactive with the La C-terminus. Using sera that were anti-Ro-positive but anti
      La-negative, 37% were reactive with the recombinant protein, 26% with the La N
      terminus, 33% with the La C-terminus and only 11 % with the synthetic peptide.
      Our results suggest that the synthetic peptide epitopes exhibit high sensitivity
      and specificity for the detection of anti-La/ SSB antibodies in ELISA and dot
      blot techniques. The peptide SOC4-(349-364aa) has the same sensitivity for the
      detection of anti-La/SSB antibodies as the recombinant protein.

PMID- 9566805
TI  - Behavioral versus pharmacological treatments of obsessive compulsive disorder: a
      meta-analysis.
AB  - The goal of the study was to provide a quantitative analysis of the relative
      efficacy of all five currently available serotonin reuptake inhibitors (SRIs) and
      behavior therapy [exposure and response prevention (ERP)] for obsessive
      compulsive disorder. The relationship between effect size and methodological
      characteristics was also empirically examined. A search was conducted of several
      computerized databases covering the dates from 1973 to 1997. Seventy-seven
      studies were identified, yielding 106 treatment comparisons involving 4641
      patients. Effect sizes were analyzed between individual interventions and between
      intervention class [SRI, ERP or the combined treatment of an SRI with
      ERP(ERP/SRI)]. Data were analyzed both before and after controlling for
      methodological variables. The effect size for clomipramine (CMI) was
      significantly greater than the other SRIs, with the exception of fluoxetine
      (FLX). CMI was not significantly greater than ERP or ERP/SRI. As a class, ERP was
      significantly greater than SRIs as a whole. Effect sizes were larger for studies
      without a control group or random assignment, for self-reported outcome measures,
      and varied significantly by method of effect size calculation. Year of
      publication was significantly related to effect size. When controlling for these
      methodological variables, CMI was not significantly greater than FLX or
      fluvoxamine (FLV), and ERP was no longer significantly greater than the SRIs as a
      whole. No significant difference was found between CMI and the other SRIs as a
      group in head to head trials. No differences in drop-out rates were found. CMI
      stands out from the other SRIs. This difference is probably not clinically
      significant enough to warrant first choice treatment, given CMI's greater
      lethality in overdose. The choice between an SRI or ERP is dominated primarily by
      the infrequent availability of ERP and to a lesser degree by personal preference.
      Methodological differences significantly impact effect size.

PMID- 9566806
TI  - Alternate-day buprenorphine dosing is preferred to daily dosing by opioid
      dependent humans.
AB  - Alternate-day buprenorphine dosing was compared to daily dosing in opioid
      dependent outpatients and choice of alternate-day versus daily dosing was
      assessed. Four dosing schedules were presented in random order under blind and
      open dosing conditions. Subjects received two exposures to each dosing schedule.
      During daily dosing, subjects received maintenance doses every 24 h. During blind
      alternate-day dosing, subjects received double maintenance doses every 48 h;
      placebo was interposed on intervening days. During open alternate-day dosing,
      subjects received twice their maintenance dose on Monday, Wednesday and Friday
      and maintenance doses on Sunday. After completing two exposures to each dosing
      schedule, subjects chose either daily or alternate-day schedules each week for 1
      month. Study participation was contingent on daily attendance and opioid
      abstinence. Ten subjects were exposed to the four conditions once. Seven subjects
      repeated these conditions and participated in the choice phase. The effects of
      daily versus alternate-day dosing were not influenced by blind or open dosing
      conditions. Subjects' ratings of withdrawal, "sick" and sedation were lower
      during daily than during alternate-day dosing, but the difference between
      treatments was small. Nonetheless, subjects still chose alternate-day dosing on
      96% of occasions, suggesting that the subject-rated differences between dosing
      schedules were not influential. These results extend prior findings to open
      dosing conditions, and replicate the safety and acceptability of alternate-day
      buprenorphine treatment. Choice of alternate-day buprenorphine administration
      underscores the procedure's clinical utility and potential use as a positive
      reinforcer to enhance opioid treatment.

PMID- 9566807
TI  - Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant
      activity in the mouse forced swimming test.
AB  - The present study was undertaken to identify the receptor subtypes involved in
      (+/-) pindolol's ability to enhance the effects of antidepressant drugs in the
      mouse forced swimming test. Interaction studies were performed with S 15535
      (presynaptic 5-HT1A receptor agonist) and methiothepin (5-HT1B autoreceptor
      antagonist) in an attempt to attenuate or potentiate antidepressant-like
      activity. (+/-) Pindolol was tested in combination with selective agonists and
      antagonists at 5-HT1, 5-HT2 and 5-HT3 receptor subtypes. Pretreatment with S
      15535 and methiothepin attenuated the activity of paroxetine, fluvoxamine and
      citalopram (32 mg/kg, i.p.; P < 0.01). (+/-) Pindolol (32 mg/kg, i.p.) induced
      significant anti-immobility effects when tested in combination with 5-methoxy-3
      (1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.; P < 0.05), 1
      (2-methoxyphenyl)-4-[-(2-phthalimido) butyl]piperazine) (NAN 190) (0.5 mg/kg; P <
      0.05) and ondansetron (0.00001 mg/kg, i.p.; P < 0.01). Pretreatment with NAN 190
      (0.5 mg/kg, i.p.) potentiated the effects of RU 24969 (1 mg/kg, i.p.; P < 0.05)
      and (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) in the forced swimming test, as did
      ondansetron (0.00001 mg/kg, i.p.). Significant additive effects were induced when
      RU 24969 (1 mg/kg, i.p.) was tested in combination with NAN 190 (0.5 mg/kg, i.p.;
      P < 0.05), (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) and ondansetron (0.0000
      mg/kg, i.p.; P < 0.05). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1
      mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.) did not induce significant
      antidepressant-like effects with any of the agonists/antagonists tested. The
      results of the present study suggest that pindolol is acting at presynaptic 5
      HT1B serotonergic receptors, in addition to the 5-HT1A subtype, in augmenting the
      activity of antidepressants in the mouse forced swimming test.

PMID- 9566808
TI  - Effect of destruction of noradrenergic neurones with DSP4 on performance on a
      free-operant timing schedule.
AB  - This experiment examined the effect of destroying central noradrenergic neurones,
      using the selective neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine], on performance in a free-operant timing schedule. Rats
      received either systemic treatment with DSP4 or vehicle-alone injections. They
      were trained to press levers for a sucrose reinforcer. Training sessions
      consisted of 40, 50-s trials in which reinforcers were available on a variable
      interval 25-s schedule; in the first 25 s of each trial, reinforcers were only
      available for responses on lever A, whereas in the last 25 s reinforcers were
      available only for responses on lever B. Data were collected from probe trials
      (four per session), in which no reinforcers were delivered, during the last ten
      of 60 training sessions. Both groups showed decreasing response rates on lever A,
      and increasing response rates on lever B, as a function of time from the onset of
      the trial. Quantitative indices of timing behaviour were derived from a two
      parameter logistic function fitted to the relative response rates on lever B
      (response rate on lever B, expressed as a percentage of overall response rate);
      this function accounted for > 90% of the data variance in each group. The DSP4
      treated group showed a significantly lower value of the indifference point (i.e.
      the time corresponding to 50% responding on lever B) than the control group. The
      slope of the function and the rate of switching between response alternatives did
      not differ significantly between the two groups. The concentrations of
      noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4
      treated group, but the concentrations of dopamine, 5-hydroxytryptamine and 5
      hydroxyindoleacetic acid were not significantly altered. It is suggested that
      results may be consistent with a role of the dorsal ascending noradrenergic
      pathway in behavioural "arousal".

PMID- 9566809
TI  - Antidepressant-associated mania: a study of anxiety disorders patients.
AB  - Antidepressants are related to the emergence of manic and hypomanic episodes in
      mood disorder patients. This study examined whether antidepressant-associated
      manic states are also present in anxiety disorder patients, so that this
      phenomenon may be defined as a side-effect. A total of 167 consecutive patients
      at a specialized outpatient clinic, suffering from anxiety disorders and treated
      by antidepressants, were assessed in a blind, retrospective chart review. Five
      patients (2.99%) were identified as having suffered an episode of antidepressant
      associated mania within 3 months of initiation of treatment. All were females and
      all had an axis II diagnosis of a cluster B personality disorder. Antidepressant
      associated mania appears to be related to risk factors such as personality
      disorder, even in non-mood disorder patients, tentatively suggesting that it is
      not simply an adverse event but rather a reflection of an underlying
      psychopathology.

PMID- 9566810
TI  - Corticotropin-releasing factor receptor blockade enhances conditioned aversive
      properties of cocaine in rats.
AB  - The behavioral profile of corticotropin-releasing factor (CRF) in mediating
      anxiogenic-like and aversive responses to stressors may be particularly relevant
      for dependence and withdrawal in drug-experienced organisms. Moreover, stressful
      aspects of drug exposure in the drug naive organism may also induce CRF system
      activation. In the present studies, the dependence of aversive properties of
      cocaine on activation of endogenous CRF systems has been evaluated in rats using
      taste conditioning and runway self-administration paradigms. Systemic cocaine
      administration (20 mg/kg i.p.) produced a conditioned saccharin aversion which
      was dose-dependently potentiated by central administration of the CRF receptor
      antagonist, D-phe CRF (12 41). In addition, i.v. cocaine administration (0.75
      mg/kg per injection i.v.) produced runway goal-box avoidance and conditioned
      place avoidance responses which were significantly accelerated by CRF antagonist
      treatment. In contrast, CRF receptor stimulation using CRF itself abolished
      cocaine-induced increases in goal latency in the runway paradigm. This
      generalized involvement of CRF systems in cocaine-related
      motivational/associative states is consistent with the comprehensive role of CRF
      in mediating emotional responses to non-drug stressors.

PMID- 9566812
TI  - Quadratic dose-response relationship between caffeine (1,3,7-trimethylxanthine)
      and EEG correlation dimension.
AB  - Many studies have failed to determine a systematic dose-response relationship
      across different cognitive tasks between caffeine and EEG power spectra. However,
      a nonlinear approach to EEG analysis, which reconstructs a multi-dimensional
      state space from each electrode recording, can be used to compute the number of
      active degrees of freedom in the signal (the correlation dimension, D2), and can
      be interpreted as a measure of signal complexity. This study attempted to
      determine a consistent dose-response relationship between caffeine and EEG D2,
      across six oral caffeine doses (100-600 mg), with each subject acting as their
      own control, to create a probabilistic bias against finding any consistent linear
      or nonlinear dose-response relationship across different cognitive tasks. The
      experiment (n = 10) was conducted with three within-subjects explanatory
      variables, 2 (experimental, placebo) x 8 (caffeine level) x 4 (type of cognitive
      task performed), with EEG D2 as the response variable, measured from Fz, F3, F4
      and Cz. A significant three-way interaction was found [F(21,245.3) = 3.65, P =
      0.001]. Regression analyses revealed a linear trend for the response variable
      across trials for the placebo condition (average R2 = 0.54), whereas
      linear+quadratic trends explained an average 30% of the variance for the
      experimental condition, compared to 0.01% for the linear fit, indicating a robust
      quadratic dose-response relationship between caffeine and EEG D2. Three
      conditions had positive quadratic co-efficients, and one condition had a negative
      quadratic co-efficient. These results are discussed in terms of the implications
      for brain dynamics, and with respect to recent criticisms of the computation of
      D2 from EEG.

PMID- 9566811
TI  - Physostigmine results in an increased decrement in brain glucose consumption in
      Alzheimer's disease.
AB  - The responsibility of cerebral cholinergic lesions for the weak clinical response
      to cholinergic neurotransmission enhancement of Alzheimer's disease (AD) was
      studied by measuring the effects of physostigmine on glucose consumption and
      neuropsychological tests. Ten AD and ten aged normals (AN) were examined twice,
      under placebo and under maximal tolerated dose of physostigmine, in randomized
      order and blind fashion. Under physostigmine, both groups showed better
      performances in tests measuring attention (P < 0.05-0.001) but not long-term
      memory, and cerebral glucose consumption was regionally modified (P < 0.0001). We
      observed a regional decrease in AD and in AN which was larger in AD, where each
      patient exhibited a mean metabolic decrease. With normalized values, AD and AN
      showed a similar decrease in the metabolic values of prefrontal cortex and
      striatum (P = 0.0003). These findings suggest that cholinergic neurotransmission
      enhancement depresses glucose consumption and increases selective attention in
      similar ways in both groups, but to a larger extent in AD. This suggests that
      brain metabolism in AD over-responds to enhancement of cholinergic
      neurotransmission. The observed weak response of clinical symptomatology to
      anticholinesterase agents does not appear to be due to the failure to enhance the
      activity of the cholinergic system in AD.

PMID- 9566813
TI  - "Depression" increases "craving" for sweet rewards in animal and human models of
      depression and craving.
AB  - This study consisted of two experiments, one in rats and one in human volunteers,
      that used the identical progressive ratio (PR) operant procedure. In both
      experiments, responding was reinforced under a progressively increasing work
      requirement, and different groups of subjects received reinforcers that varied in
      sweetness. In experiment 1, rats were subjected to chronic mild stress, a well
      validated animal model of depression. Performance under the PR schedule increased
      in subjects reinforced with conventional precision pellets (which contain 10%
      sucrose) or very sweet pellets, but not in subjects reinforced with sugar-free
      pellets. In experiment 2, volunteers were subjected to a depressive musical mood
      induction. Performance under the PR schedule increased in subjects reinforced
      with chocolate buttons, but not in subjects reinforced with with buttons made
      from the relatively unpalatable chocolate substitute carob. In experiment 2,
      depressive mood induction also increased chocolate craving, as measured by a
      novel questionnaire, and there were significant correlations between chocolate
      craving and chocolate-reinforced PR performance. These results suggest that
      performance under the PR schedule provides a measure of craving rather than
      reward, and that craving for sweet rewards is increased by depressive mood
      induction in both animal and human models. Implications for the interpretation of
      pharmacological studies using the PR procedure are also discussed.

PMID- 9566814
TI  - Heterogeneity of behavioural profile between three new putative selective D3
      dopamine receptor antagonists using an ethologically based approach.
AB  - The effects on behaviour of the putative selective D3 dopamine receptor
      antagonists GR 103691, nafadotride and U 99194A were compared with those of the
      generic D2-like antagonist haloperidol, using an ethologically based approach.
      Neither GR 103691 (0.008-1.0 mg/kg) nor nafadotride (0.025-1.6 mg/kg) influenced
      any element of behaviour. Conversely, U99194A (1.67-45 mg/kg) effected a dose
      dependent stimulation of episodes of non-stereotyped sniffing, locomotion,
      chewing and eating, with some stimulation of rearing, and reduced baseline levels
      of grooming; thereafter, as sniffing and locomotion declined, stimulation of
      episodes of grooming emerged. Haloperidol (0.0008-0.1 mg/kg) failed to promote
      any element of behaviour and reduced baseline levels of grooming; responsivity to
      U99194A was antagonised by pretreatment with haloperidol. The lack of effect of
      GR 103691 (> 100-fold D3/D2 selectivity) and nafadotride (10-fold D3/D2
      preference), in contrast to the characteristic "ethogram" for U99194A (25-fold
      D3/D2 selectivity), indicated a fundamental difference in their mechanisms of
      action. This topography of responsivity to U99194A overlapped somewhat with the
      profiles of both D2-like and D1-like agonists, and its sensitivity to antagonism
      by haloperidol also indicated a dopaminergic basis thereto. However, differences
      among GR 103691, nafadotride and U99194A bore no relation to their relative
      selectivities for the D3 receptor, and the basis thereof remains unclear.
      Theorising as to the behavioural role of the D3 receptor may need to be tempered
      pending the identification of a range of chemically distinct D3 antagonists of
      higher selectivity.

PMID- 9566815
TI  - mCPP-induced anxiety in the light-dark box in rats--a new method for screening
      anxiolytic activity.
AB  - The activity of anxiolytic and other drugs in a light-dark test situation was
      studied in rats treated with the anxiogenic compound m-chlorophenyl-piperazine
      (mCPP). mCPP 0.5 mg/kg significantly diminished the exploratory activity of the
      animals in the light compartment of the apparatus. Drugs to be tested against
      mCPP-induced anxiety when studied alone (not in combination with mCPP) did not
      significantly alter the activity of rats in the light-dark apparatus, except
      yohimbine, which reduced the movement time values in the lit area. 1,4
      Benzodiazepines [diazepam (0.1-4mg/kg) and chlordiazepoxide (2-8mg/kg)], 5
      HT2A/2C antagonists [ritanserin (0.25-8 mg/kg) and deramciclane (0.5-8 g/kg)],
      the 5-HT3 antagonist MDL-72222 (3 mg/kg) and ethanol (2-4 mg/kg) significantly
      reduced the effect of mCPP. A dose-dependent increase in the exploratory activity
      of mCPP-treated animals was found in the 2,3-benzodiazepine girisopam (2.5-5
      mg/kg)-treated groups. Tofisopam, another 2,3-benzodiazepine molecule, also
      showed activity against mCPP, although its effect was not statistically
      significant. The 5-HT1A partial agonist buspirone was also active in the dose
      range of 0.25-0.5 mg/kg, while the 5-HT1A full agonist 8-OH-DPAT was the only
      drug with presumed anxiolytic activity that clearly lacked any effect in this
      model. Imipramine, amitriptyline, morphine, naloxone, haloperidol, clozapine,
      amphetamine, yohimbine, carbamazepine and diphenylhydantoin were not effective.
      We conclude that mCPP-induced anxiety in the light-dark box is a potent and
      useful method for screening and detecting anxiolytic activity of a wide range of
      compounds with various modes of action.

PMID- 9566816
TI  - A partial noradrenergic lesion induced by DSP-4 increases extracellular
      noradrenaline concentration in rat frontal cortex: a microdialysis study in vivo.
AB  - The effect of systemic administration of the selective neurotoxin N-(2
      chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on noradrenaline efflux in the
      frontal cortex was studied in freely-moving rats using microdialysis in vivo.
      Five days after treatment with DSP-4 (40 mg/kg i.p.), the noradrenaline content
      of the frontal cortex was reduced by 75%. Yet, noradrenaline efflux in the
      frontal cortex was nearly two-fold greater in DSP-4 treated rats than in saline
      injected controls. Local infusion of the noradrenaline-selective uptake blocker,
      desipramine (5 microM), via the microdialysis probe, increased noradrenaline
      efflux in rats from both groups. Perfusion of Ringer's solution, containing 80 mM
      K+, also increased noradrenaline efflux in both groups, but the increase after
      DSP-4 pretreatment was greater than in the controls. In contrast, removal of Ca2+
      from the infusion medium reduced noradrenaline efflux in both treatment groups.
      These results indicate that, at this dose, DSP-4 increases the extracellular
      concentration of noradrenaline in rat frontal cortex despite causing a partial
      lesion of noradrenergic neurones. This is due to an increase in the release of
      noradrenaline, although reduced clearance is also likely. These data challenge
      the assumption that depletion of noradrenaline content after treatment with DSP-4
      invariably translates into diminished noradrenergic transmission.

PMID- 9566817
TI  - Infusion of the serotonin1B (5-HT1B) agonist CP-93,129 into the parabrachial
      nucleus potently and selectively reduces food intake in rats.
AB  - Unilateral infusion of the selective 5-HT1B agonist, CP-93,129 (3-(1,2,5,6
      tetrahydropyrid-4-yl) pyrrolo[3,2-b]pyrid-5-one) into the parabrachial nucleus
      (PBN) of the pons reduced food consumption by rats. The hypophagia was dose
      related (ED50 approximately 1 nmol) and associated with fewer observations of
      feeding and more periods of inactivity. Water intake, grooming and exploratory
      activity were unaffected. CP-93,129 also decreased food intake when injected into
      the hypothalamic paraventricular nucleus, but this action was 50-fold less potent
      than administration into the PBN. Autoradiography demonstrated 5-HT1B sites in
      the PBN; this binding was displaced by CP-93,129. The results implicate
      parabrachial 5-HT1B receptors in mediating serotonergic enhancement of satiation.

PMID- 9566818
TI  - Sensitisation to repeated withdrawal, in mice treated chronically with diazepam,
      is blocked by an NMDA receptor antagonist.
AB  - Mice were treated either with diazepam (15 mg/kg s.c. in oil), for 21 days, or
      for 3x7-day periods interspersed with two 72-h drug-free periods. Convulsant
      thresholds to pentylentetrazole infused into the tail vein 72 h following the
      final chronic treatment were lower in multiple-withdrawal mice than in mice which
      had experienced the same drug load, but only a single withdrawal, consistent with
      sensitisation of withdrawal events following previous withdrawal experience. The
      increase in seizure sensitivity of repeatedly withdrawn mice was prevented by
      treatment with the NMDA receptor antagonist CGP 39551 (20 mg/kg, i.p.) given once
      daily during the 3-day breaks in diazepam treatment, suggesting a role of
      glutamatergic transmission in the sensitisation process.

PMID- 9566819
TI  - Long-term course of interferon-treated chronic hepatitis C.
AB  - BACKGROUND/AIMS: To evaluate whether sustained response to a-interferon improves
      clinical outcome in patients with chronic hepatitis C. METHODS: A cohort of 410
      consecutive patients (65% with chronic hepatitis, 35% with cirrhosis) were
      treated with a-interferon in two trials (mean follow-up 62.1 months, range 7-109
      months). All were serum HCV RNA positive before therapy and received first 10
      then 5 million units of a-2b or a-nl interferon three times weekly for 6 to 12
      months. Sustained response was defined as normal aminotransferases 12 months
      after stopping interferon. RESULTS: Sixty-two patients (15.1%: 54 with chronic
      hepatitis, eight with cirrhosis) were sustained responders. At the end of follow
      up, 56 out of 62 sustained responders (90.3%) were serum HCV RNA negative. No
      biochemical relapse after 12 months was seen in sustained responders, regardless
      of initial histology, HCV genotype or persistence of HCV RNA. Although three died
      of non-hepatic causes, no liver-related events were observed among sustained
      responders. Complications of liver disease occurred in 34 relapsers/non
      responders: nine hepatocellular carcinomas, 21 ascites and four portal
      hypertensive bleedings. Eleven relapsers/nonresponders died: eight of hepatic and
      three of non-hepatic causes. Event-free survival was significantly longer in
      sustained responders than in all the remaining patients. In a regression
      analysis, sustained response to interferon, low age and absence of cirrhosis were
      independent predictors of event-free survival. CONCLUSIONS: Hepatitis C virus is
      probably eradicated and progression of liver disease is prevented in most
      patients who remain HCV RNA negative with normal transaminases for more than 1
      year after stopping treatment.

PMID- 9566820
TI  - Pattern of HCV antibodies with special reference to NS5A reactivity in HCV
      infected patients: relation to viral genotype, cryoglobulinemia and response to
      interferon.
AB  - BACKGROUND/AIMS: We aimed to compare the anti-hepatitis C virus reactivity in
      confirmatory assays (RIBA 3.0 Ortho Diagnostic and INNO-LIA HCV Ab III
      Innogenetics) among patients infected with different hepatitis C virus genotypes,
      with or without cryoglobulinemia, and in patients treated with interferon.
      METHODS: One hundred and three patients followed in our hepatogastroenterology
      unit were included in the study and compared to 320 consecutive patients tested
      using RIBA 3.0. Seventy-nine of the 103 patients were treated with interferon.
      Long-term responders to interferon were defined as having normal alanine
      aminotransferase levels and being HCV RNA negative 6 months after the end of
      treatment. Initial responders were defined as having normal alanine
      aminotransferase levels at the end of interferon therapy but abnormal alanine
      aminotransferase levels and/or detectable HCV RNA during the following 6 months.
      Non-responders were defined as still having elevated alanine aminotransferase
      during and after interferon. Serological tests (RIBA and INNO-LIA) were performed
      according to the manufacturers' instructions. HCV RNA was detected by nested
      polymerase chain reaction. Hepatitis C virus genotype was determined by using a
      Line Probe Assay (Innogenetics). RESULTS: There was no significant difference in
      the pattern of hepatitis C virus reactivity according to the hepatitis C virus
      genotype or presence of cryoglobulinemia. Twenty-three patients were classified
      as non-responders, 35 as initial responders, 21 as long-term responders. NS5
      reactivity was significantly different (p<0.01) between these three groups: 34%
      of non-responders (8/23) had RIBA 3.0 NS5 reactivity and 13% (3/23) were reactive
      in the INNO-LIA III. Almost all long-term responders (95%) had NS5 reactivity by
      both RIBA 3.0 and INNO-LIA III. CONCLUSION: We conclude that patients who respond
      to interferon have stronger reactivity against NS5 antigens than non-responders.
      Molecular changes in the NS5A region may be responsible for such differences, as
      recently suggested.

PMID- 9566821
TI  - Ultrasound detection of abdominal lymphadenomegaly in subjects with hepatitis C
      virus infection and persistently normal transaminases: a predictive index of
      liver histology severity.
AB  - BACKGROUND/AIMS: The indications for liver biopsy in anti-HCV-positive patients
      with persistently normal alanine aminotransferase levels are not clearly
      established. Recent studies have correlated the presence of abdominal
      lymphoadenomegaly with disease severity in patients with chronic hepatitis C. Our
      study aimed to evaluate the frequency of abdominal lymphoadenomegaly in an anti
      HCV positive blood donor population with persistently normal alanine
      aminotransferase and the relationship of abdominal lymphoadenomegaly with the
      severity of liver changes. METHODS: Eighty-six anti-HCV positive blood donors (58
      M, 28 F) with normal alanine aminotransferase were followed up for a median of 31
      months (range 12-50). To evaluate the frequency of abdominal lymphoadenomegaly,
      all patients underwent ultrasound scan. The common parameters of liver function
      as well as serum HCV RNA levels were determined. Histological changes were
      evaluated both in a conventional manner and using the numerical scoring systems
      of Knodell and Desmet. RESULTS: Of the 86 donors, 68 (79%) maintained
      persistently normal alanine aminotransferase levels during follow-up, and
      abdominal lymphoadenomegaly was present in 15 of them (22.0%). The remaining 18
      donors (21%) showed rises in alanine aminotransferase above normal levels during
      the follow-up and seven of them (38%) had abdominal lymphoadenomegaly (p=n.s.).
      In the subjects with normal alanine aminotransferase, there were no significant
      differences in the common parameters of liver function and the serum presence of
      HCV RNA between those with or without abdominal lymphoadenomegaly. Normal liver
      was found in five patients without abdominal lymphoadenomegaly, but never in
      patients with abdominal lymphoadenomegaly. Analysis with the Mantel-Haenszel test
      showed a trend toward more serious changes in patients with abdominal
      lymphoadenomegaly (chi-square MH=9.5, p<0.003). Histological changes did not
      differ when Knodell's score was used; in contrast, staging, evaluated by Desmet's
      score, and periportal necrosis were significantly higher in subjects with
      abdominal lymphoadenomegaly (p<0.01 and p<0.004, respectively). Multiple logistic
      regression showed a significant relation between histological changes and the
      presence in serum of HCV RNA (p<0.004) and gamma-globulin (p<0.002), and
      abdominal lymphoadenomegaly p<0.003). CONCLUSION: Our study shows a prevalence of
      22.0% of abdominal lymphoadenomegaly in anti-HCV positive subjects with normal
      alanine aminotransferase values and a relationship with the degree of liver
      histology change. Therefore, we suggest that the evidence of abdominal
      lymphoadenomegaly in these patients could be an indication to perform liver
      biopsy.

PMID- 9566822
TI  - High prevalence of infection with hepatitis G virus in patients with hepatic and
      extrahepatic malignancies.
AB  - BACKGROUND/AIMS: The pathogenic role of hepatitis G virus, the recently
      discovered blood-borne agent, is controversial. Our aim was to ascertain the
      prevalence of hepatitis G virus infection in hepatic and in extrahepatic
      malignancies. METHODS: We studied 166 Italian patients (112 male, 54 female, mean
      age 61.8+/-9.3, mean+/-SD, range 34-85). One hundred and eighteen had cirrhosis,
      which was complicated by hepatocellular carcinoma in 66 cases. Forty-eight
      patients had extra-hepatic malignancies. Circulating HGV RNA was detected by
      reverse transcriptase-polymerase chain reaction (RT-PCR) of both the
      nonstructural-3 and 5'noncoding regions of the hepatitis G virus genome.
      Antibodies to the E2 protein of hepatitis G virus were detected by means of an
      enzyme-linked immunosorbent assay. RESULTS: Ongoing HGV infection was detected in
      30/66 (46%) patients with hepatocellular carcinoma, 12/52 (23%) patients with
      cirrhosis, and 14/48 (29%) patients with extrahepatic malignancies (p<0.05).
      Evidence of exposure to hepatitis G virus (detection of either HGV RNA or anti-E2
      antibodies) was found in 46% of patients with cirrhosis, 66% of patients with
      hepatocellular carcinoma, and 39% of patients with extrahepatic malignancies.
      Serum HGV RNA positivity was associated with a hematocrit value < or = 0.35 and
      with history of exposure to blood products (p<0.005). CONCLUSIONS: Ongoing
      hepatitis G virus infection is detected at a very high rate in patients with
      hepatocellular carcinoma, but is also fairly common in extrahepatic malignancies.
      Hepatitis G virus infection in these patients is likely to originate from
      exposure to blood products, and to persist because of deficient immune
      surveillance.

PMID- 9566823
TI  - Liver failure associated with mitochondrial DNA depletion.
AB  - BACKGROUND/AIMS: Liver failure in infancy can result from several disorders of
      the mitochondrial respiratory chain. In some patients, levels of mitochondrial
      DNA are markedly reduced, a phenomenon referred to as mitochondrial DNA
      depletion. To facilitate diagnosis of this condition, we have reviewed the
      clinical and pathological features in five patients with mitochondrial DNA
      depletion. METHODS: Cases were identified by preparing Southern blots of DNA from
      muscle and liver, hybridising with appropriate probes and quantifying
      mitochondrial DNA relative to nuclear DNA. RESULTS: All our patients with
      mitochondrial DNA depletion died of liver failure. Other problems included
      hypotonia, hypoglycaemia, neurological abnormalities (including Leigh syndrome)
      and cataracts. Liver histology showed geographic areas of fatty change, bile duct
      proliferation, collapse of liver architecture and fibrosis; some cells showed
      decreased cytochrome oxidase activity. Muscle from three patients showed
      mitochondrial proliferation, with loss of cytochrome oxidase activity in some
      fibres but not in others; in these cases, muscle mitochondrial DNA levels were
      less than 5% of the median control value. The remaining two patients (from a
      single pedigree) had normal muscle histology and histochemistry associated with
      less severe depletion of mitochondrial DNA in muscle. CONCLUSIONS: Liver failure
      is common in patients with mitochondrial DNA depletion. Associated clinical
      features often include neuromuscular disease. Liver and muscle histology can be
      helpful in making the diagnosis. Mitochondrial DNA levels should be measured
      whenever liver failure is thought to have resulted from respiratory chain
      disease.

PMID- 9566824
TI  - Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among
      alcoholics.
AB  - BACKGROUND/AIMS: Animal studies have shown that the induction of cytochrome
      P4502E1 (CYP2E1) modulates oxidative damage induced by ethanol. Since CYP2E1
      activity varies substantially in humans, we have investigated whether differences
      in CYP2E1 activity might influence the formation of hydroxyethyl free radicals
      and the stimulation of lipid peroxidation among alcohol abusers. METHODS:
      Chlorzoxazone oxidation, an index of CYP2E1 activity, and the levels of
      antibodies reacting with hydroxyethyl radical and malonyldialdehyde protein
      adducts were investigated in 51 alcoholic patients. RESULTS: We observed that in
      40 out of 51 (78%) alcoholics, chlorzoxazone oxidation was increased over the
      control levels, consistently with CYP2E1 induction by ethanol. However, in the
      remaining 22% of the patients, in spite of a similar alcohol intake,
      chlorzoxazone oxidation was within the control range, indicating a lack of CYP2E1
      inducibility. IgG reacting with hydroxyethyl free radical-protein adducts were
      absent in subjects without CYP2E1 induction, while they were significantly
      increased in alcoholics with induced CYP2E1 activity. IgG against
      malonyldialdehyde protein-adducts were increased in all patients, irrespective of
      CYP2E1 inducibility. Moreover, chlorzoxazone oxidation was significantly lower in
      alcoholics without clinical and biochemical signs of liver disease as compared to
      patients with alcoholic liver disease. CONCLUSIONS: These results indicate that
      CYP2E1 activity greatly influences the formation of hydroxyethyl radicals in
      humans, and suggest a possible role of CYP2E1 in the development of alcoholic
      liver disease.

PMID- 9566825
TI  - Differential expression of transforming growth factor-beta and its receptors in
      hepatocytes and nonparenchymal cells of rat liver after CCl4 administration.
AB  - BACKGROUND/AIMS: Transforming growth factor-beta (TGF-beta) is a family of
      multifunctional proteins that regulate hepatocyte proliferation, and biosynthesis
      of the extracellular matrix. In this study we examined whether modulation of TGF
      beta receptor expression contributes to the liver diseases. METHODS: The mRNA
      expression of TGF-beta1, TGF-beta type I receptor (TGFbetaRI), TGF-beta type II
      receptor (TGFbetaRII) and TGF-beta type III receptor (TGFbetaRIII) in rat livers
      injured by CCl4 administration was studied by Northern blotting. The mRNA
      expression patterns were confirmed by in situ hybridization. RESULT: The peak of
      TGF-beta1 mRNA expression was observed 48 h after acute intoxication with CCl4 in
      nonparenchymal cells. However, the levels of TGFbetaRI and TGFbetaRII mRNA
      expression decreased from 24 h to 48 h and from 12 h to 48 h, respectively, and
      returned to the normal level by 72 h. TGFbetaRII mRNA expression was depressed
      more and for longer than that of TGFbetaRI mRNA. Analysis in separated
      hepatocytes and nonparenchymal cells from the injured livers indicated that the
      mRNA changes occurred in hepatocytes. Nonparenchymal cells expressed TGFbetaRI
      and TGFbetaRII mRNAs at constant levels during liver regeneration. TGFbetaRIII
      mRNA, which also decreased after 12 h, was not apparent in hepatocytes but only
      in nonparenchymal cells. CONCLUSIONS: These observations suggest that: (i)
      whenever TGF-beta1 is increased in CCl4-treated livers, it may induce liver
      fibrogenesis via nonparenchymal cells; (ii) the mitoinhibitory effect of TGF
      beta1 on hepatocytes is transiently relieved by down-regulation of TGF-beta
      receptors for 72 h post-damage; and (iii) the resistance to TGF-beta growth
      inhibition between 24 to 48 h may be predominantly due to down-regulation of the
      expression of TGFbetaRII.

PMID- 9566826
TI  - Immunogenetic analysis of a panel of monoclonal IgG and IgM anti-PDC-E2/X
      antibodies derived from patients with primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Autoantibodies with specificity for the E2 component of the
      pyruvate dehydrogenase complex (PDC-E2) are commonly present in primary biliary
      cirrhosis. The aim of this study was to generate and characterise human anti-PDC
      E2 monoclonal antibodies and analyse immunoglobulin gene usage and mutation for
      clues to pathogenesis. METHODS: Peripheral B-lymphocytes from two patients with
      primary biliary cirrhosis were used to generate heterohybridomas secreting PDC-E2
      specific monoclonal antibodies. The antibodies were characterised by ELISA,
      immunoblotting, indirect immunofluorescence and enzyme inhibition techniques, and
      their encoding immunoglobulin genes were amplified, cloned and sequenced.
      RESULTS: Four IgGlambda and one IgMlambda monoclonal antibodies specific for PDC
      E2 were generated: all gave bands at 74 kD and 52 kD on PDC immunoblots, two
      clones were specific for the lipoylated inner lipoyl domain, and all inhibited
      target enzyme function. Sequence analysis suggested unrestricted VH gene usage,
      but a strong preference for lambda light chains. The extent of somatic mutation
      was high (3-20%), with evidence for antigen selection in 3/5 VH sequences.
      CONCLUSIONS: These monoclonal antibodies closely resemble the hallmark
      autoantibodies of primary biliary cirrhosis. Their specificities demonstrate true
      cross reactivity between an epitope on PDC-E2 and Protein X, and the existence of
      a subset of B cells that recognise only the lipoylated form of the antigen. The
      pattern of immunoglobulin gene mutations suggests an antigen-driven selection of
      high affinity IgG autoantibodies, supporting a possible role for exogenous
      antigen in the pathogenesis of primary biliary cirrhosis.

PMID- 9566827
TI  - Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in
      humans.
AB  - BACKGROUND/AIMS: Acute hyperglycemia inhibits gallbladder contraction. In non
      diabetic subjects this inhibitory effect may result from endogenous
      hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia
      and euglycemic hyperinsulinemia on basal and cholecystokinin-stimulated
      gallbladder motility. METHODS: Gallbladder volume (ultrasonography) and duodenal
      bilirubin output were studied simultaneously in nine healthy volunteers (age 20
      52 years) on 3 separate occasions in random order during: (a) saline infusion
      (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15
      mmol/l), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150
      mU/l, glucose at 4-5 mmol/l). After a 2-h basal clamp period, cholecystokinin was
      infused intravenously for 60 min at 0.25 IDU x kg(-1) x h(-1), followed by
      another 60 min at 0.5 IDU x kg(-1) x h(-1). RESULTS: HI and HG significantly
      (p<0.05) reduced basal duodenal bilirubin output compared to control, while basal
      gallbladder volume did not change. At the low dose cholecystokinin, gallbladder
      emptying during HG (25+/-3%) and HI (39+/-4%) was significantly (p<0.01) reduced
      compared to control (61+/-4%). The inhibitory effect of HG was significantly
      (p<0.05) stronger compared to HI. Duodenal bilirubin output during the low dose
      cholecystokinin was significantly (p<0.05) reduced by HG, but not by HI. No
      inhibitory effect of HG and HI on gallbladder emptying and duodenal bilirubin
      output was observed with the high dose of cholecystokinin. CONCLUSIONS: In
      healthy subjects acute hyperglycemia and euglycemic hyperinsulinemia reduce basal
      duodenal bilirubin output and inhibit gallbladder emptying stimulated by low dose
      cholecystokinin. These results suggest that insulin is involved in the inhibitory
      effect of hyperglycemia on basal and cholecystokinin-stimulated gallbladder
      motility.

PMID- 9566828
TI  - Diverse morphology of biliary atresia in an animal model.
AB  - BACKGROUND/AIMS: Extrahepatic biliary atresia can be simulated in Balb/c-mice
      which have been infected with rotavirus. Irreversible occlusion of the common
      bile duct is the result of an inflammatory process of the whole biliary tract.
      The observations in this animal model are similar to extrahepatic biliary atresia
      in newborn children. The present study describes the wide range of morphological
      findings in mice and compares the results with several classifications of
      extrahepatic biliary atresia in children. METHODS: Newborn Balb/c-mice were
      infected intraperitoneally with rhesus rotavirus; the pathological morphology of
      the extrahepatic bile ducts in 73 mice is described and illustrated by scanning
      electron microscopy. RESULTS: The extension and localisation of atresia varied
      from short to interrupted or long-segment atresia, with or without prestenotic
      dilatation. The gallbladder was small and atretic, or appeared hydropic due to
      atresia of the common bile duct. The wide range of pathomorphological findings is
      the final stage of an inflammatory process. The morphological changes of the
      extrahepatic bile ducts do not fit any pattern, and no classification is evident.
      CONCLUSIONS: Most types of extrahepatic biliary atresia in children can be
      mimicked in this animal model. Comparing these observations with different
      classifications of extrahepatic biliary atresia in children, it must be asked if
      any classification of the disease is justified, having regard only to
      pathomorphological findings in the extrahepatic biliary tract.

PMID- 9566829
TI  - Attributable risk for symptomatic liver cirrhosis in Italy. Collaborative Groups
      for the Study of Liver Diseases in Italy.
AB  - BACKGROUNDS/AIMS: Knowledge of the proportion of liver cirrhosis attributable to
      the main risk factors is largely based on methodologically questionable clinical
      reports. METHODS: The proportion of newly diagnosed cases of symptomatic liver
      cirrhosis attributable to known risk factors was estimated by a case-control
      study performed during 1989-1996 in 23 medical divisions of several hospitals
      distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted
      for the first time for liver decompensation. Controls were 651 patients admitted
      during the same period and to the same hospitals as the cases, for acute diseases
      unrelated to alcohol and virus infection. The proportion of symptomatic liver
      cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the
      combination of these was expressed as the population attributable risk. RESULTS:
      Attributable risks were 67.9% (95% confidence interval (CI): 53.8-79.4) for
      alcohol, 40.1% (95% CI: 35.3-45.2) for hepatitis C virus and 4.4% (95% CI: 2.5
      7.6) for hepatitis B virus. The three factors together explained 98.1% (95% CI:
      81.6-99.6) of cases in men and 67.0% (95% CI: 50.4-85.8) in women. CONCLUSIONS:
      Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis
      risk in Italy. From a public health viewpoint, with the elimination of the well
      known risk factors (particularly alcohol and hepatitis C virus), liver cirrhosis
      should become a rare disease.

PMID- 9566831
TI  - Doppler sonography and hepatic vein catheterization in portal hypertension:
      assessment of agreement in evaluating severity and response to treatment.
AB  - BACKGROUND/AIM: The study was designed to assess to what extent portal
      hemodynamic parameters obtained by duplex Doppler ultrasonography may be
      substituted for the measurement of hepatic venous pressure gradient in evaluating
      the severity of portal hypertension and the response to medical treatment with
      beta-blockers or beta-blockers plus nitrates in patients with cirrhosis and
      portal hypertension. METHODS: In 39 of these patients hepatic venous pressure
      gradient was determined by hepatic vein catheterization, and portal blood flow
      velocity and the congestion index of the portal vein were measured by duplex
      Doppler ultrasonography. In 19 of these patients the changes in hepatic venous
      pressure gradient and in Doppler parameters were also assessed after chronic
      administration of nadolol. In 11 of the 19 patients the changes after chronic
      administration of nadolol plus isosorbide-5-mononitrate were also measured.
      RESULTS: In the whole series, no significant correlation was found between
      hepatic venous pressure gradient and duplex Doppler parameters, but, when the 12
      patients with a patent para-umbilical vein were excluded, significant linear
      correlations were found between hepatic venous pressure gradient and portal blood
      velocity (r=-0.39; p=0.05) or congestion index (r=0.37; p=0.05). Considering
      together the changes induced by nadolol and nadolol plus isosorbide-5
      mononitrate, no correlation was apparent between changes in duplex Doppler
      parameters and in hepatic venous pressure gradient. Agreement between hepatic
      venous pressure gradient and duplex Doppler parameters in defining good and poor
      responders was insufficient. CONCLUSIONS: These data suggest that portal blood
      velocity and the congestion index of the portal vein are related to portal
      hypertension in patients without a patent para-umbilical vein, but are of limited
      value in discriminating good responders from poor responders to medical treatment
      for portal hypertension.

PMID- 9566830
TI  - Effects of silymarin in alcoholic patients with cirrhosis of the liver: results
      of a controlled, double-blind, randomized and multicenter trial.
AB  - BACKGROUND/AIMS: Silymarin has protective effects in different experimental
      conditions, but its efficacy in human liver cirrhosis has not been completely
      established. Therefore, this study was carried out to determine the effect of
      silymarin in alcoholics with liver cirrhosis with respect to survival and
      clinical and laboratory changes. METHODS: From February 1986 to June 1989, we
      enrolled 200 alcoholics with histologically or laparoscopically proven liver
      cirrhosis in a randomized, double-blind multicenter trial comparing 450 mg of
      silymarin (150 mg/ three times per day) with placebo. The primary outcome was
      time to death, and the secondary outcome was the progression of liver failure.
      Additional analyses were also performed in 75 patients in whom anti-hepatitis C
      virus antibodies were measured after completion of the trial. RESULTS: One
      hundred and three patients were assigned to receive silymarin and 97 to receive
      placebo. The two groups were well matched for demographic and baseline clinical
      and laboratory features. A 2-year study period was completed in 125 patients (57
      receiving silymarin and 68 receiving placebo). Twenty-nine patients (15 receiving
      silymarin, and 14 receiving placebo) died during the trial. Survival was similar
      in patients receiving silymarin or placebo. The effect of silymarin on survival
      was not influenced by sex, the persistence of alcohol intake, the severity of
      liver dysfunction or by the presence of alcoholic hepatitis in the liver biopsy.
      Silymarin did not have any significant effect on the course of the disease. No
      relevant side-effects were observed in any group. CONCLUSIONS: The results of
      this study indicate that silymarin has no effect on survival and the clinical
      course in alcoholics with liver cirrhosis.

PMID- 9566832
TI  - The postprandial portal flow is related to the severity of portal hypertension
      and liver cirrhosis.
AB  - BACKGROUND/AIMS: Diminished postprandial portal hyperemia has been demonstrated
      by echo-Doppler flowmetry in patients with liver cirrhosis, but its diagnostic
      role is unclear. This prospective study was therefore undertaken in patients with
      varying severity of portal hypertension and degree of liver cirrhosis. METHODS:
      Portal flowmetry was performed in 66 patients with cirrhosis and 20 healthy
      volunteers during fasting and 30 min after ingestion of a standardized meal.
      Hemodynamic parameters were related to the degree of esophageal varices, variceal
      bleeding, portal hypertensive gastropathy and Child-Pugh score. RESULTS: The
      postprandial portal blood velocity increment was low in patients with esophageal
      varices of any degree (22-24%), compared to patients without varices (49%,
      p<0.01) and healthy controls (65%, p<0.001), but was not different in patients
      with or without variceal bleeding (22% vs. 20%). In contrast, the congestion
      index (CI; ratio of portal vein cross-sectional area and portal blood velocity)
      pre-/postprandial decreased in the bleeding group only (CI pre/ CI post 1.30+/
      0.23 (no bleeding) vs. 0.86+/-0.29 (bleeding); p<0.01). Portal hypertensive
      gastropathy was not related to any of the portal flow parameters. The portal
      blood velocity increment was comparable in controls (65%) and patients with Child
      Pugh class A cirrhosis (56%), but lower in patients with class B (32%) and class
      C cirrhosis (15%, p<0.05 vs. class A). Also, there was no postprandial decrease
      in congestion index in patients with the most severe cirrhosis (p<0.01 class C
      vs. class A and B). CONCLUSIONS: The postprandial rise in portal flow is
      inversely related to the severity of portal hypertension and liver cirrhosis, and
      may be a valuable parameter with respect to the risk of variceal bleeding.

PMID- 9566833
TI  - Hemodynamic changes in patients developing effective hypovolemia after total
      paracentesis.
AB  - BACKGROUND/AIMS: In many centers paracentesis is considered the treatment of
      choice for tense ascites. However, the mechanism of effective hypovolemia after
      paracentesis, the main complication associated with this procedure, remains
      unknown. In the current study, systemic hemodynamics was sequentially studied
      before and after total paracentesis in 46 patients with cirrhosis and tense
      ascites. The aim of the study was to assess the mechanism of effective
      hypovolemia after paracentesis. METHODS: Plasma renin activity and aldosterone,
      mean arterial pressure, cardiac output (ECO-Doppler) and systemic vascular
      resistance were measured before, and 3 h, 6 h and 6 days after total paracentesis
      associated with plasma volume expansion. RESULTS: Effective hypovolemia after
      paracentesis (defined as 50% increase in plasma renin activity up to a level over
      4 ng x m(-1) x h(-1) at the 6th day after paracentesis) occurred in 20 cases
      [plasma renin activity increased from 8+/-17 to 19+/-2.7 ng x m(-1) x h(-1)]. In
      the remaining 26 cases no changes in plasma renin activity [8.5+/-2.4 vs. 8.7+/
      2.2 ng x m(-1) x h(-1)] were observed. The amounts of ascitic fluid volume
      removed were similar. Effective hypovolemia after paracentesis was associated
      with a significant decrease in mean arterial pressure (89+/-2 vs. 81+/-3 mmHg)
      and systemic vascular resistance [1263+/-67 vs. 1014+/-80 dyn x s(-1) x cm(-5)] 6
      days after treatment. In contrast, no significant changes in these parameters
      were observed in patients not developing this complication. In the whole group of
      patients a significant inverse relation was observed between changes in plasma
      renin activity and in systemic vascular resistance (r=0.74;p< 0.001).
      CONCLUSIONS: These results indicate that effective hypovolemia after paracentesis
      in cirrhosis is predominantly due to an accentuation of the arteriolar
      vasodilation already present in these patients.

PMID- 9566834
TI  - The number connection tests A and B: interindividual variability and use for the
      assessment of early hepatic encephalopathy.
AB  - BACKGROUND/AIMS: The number connection tests A and B are regarded as sensitive
      psychometric measures for the assessment of early hepatic encephalopathy. Review
      of the studies dealing with the diagnostic sensitivity of the number connection
      tests, however, shows that the scoring of the number connection tests results
      differs between studies. Most groups define the limits of the normal range by
      studying small control groups. Others use scores given in the literature without
      ensuring the comparability of the test versions used. Thus, there is a need for
      normative data for the number connection test results and for re-evaluation of
      the sensitivity of the tests using valid scores. METHODS: In this study the
      number connection tests A and B were administered to 249 healthy volunteers (age:
      18 to 76 years) to analyze the influence of age, education and occupation on
      their results. In addition, the age-corrected normative data were applied to 169
      patients with grade 0-I hepatic encephalopathy. The specificity and sensitivity
      of age-corrected and age-independent normative data of the number connection
      tests were compared. RESULTS: There was a significant influence of age and
      education on the number connection test results, but only a negligible effect of
      occupation. Application of the age-corrected normative data to the test results
      of the patients with grade I hepatic encephalopathy significantly decreased the
      sensitivity of the number connection tests for hepatic encephalopathy compared to
      widely used age-independent normal ranges, but also increased the specificity.
      CONCLUSION: The use of standardized versions of the number connection tests and
      age-related normative data is recommended.

PMID- 9566835
TI  - Effects of supplementation with unsaturated fatty acids on plasma and membrane
      lipid composition and platelet function in patients with cirrhosis and defective
      aggregation.
AB  - BACKGROUND/AIMS: Defective platelet aggregation and reduced platelet production
      of thromboxane A2, a metabolite of arachidonic acid, are common findings in
      patients with cirrhosis. We evaluated the effects of dietary supplementation with
      two combinations of unsaturated fatty acids on platelet function and plasma and
      membrane fatty acids in patients with liver cirrhosis. METHODS: In a double-blind
      study, 15 patients with cirrhosis and defective aggregation were randomized to
      receive a 6-week supplementation with gamma-linolenic and linoleic acid (1 g/day
      of each fatty acid) or with oleic acid and linoleic acid (groups GLA and OA,
      respectively). RESULTS: Under baseline conditions, patients showed elevated
      concentrations of monounsaturated fatty acids and a reduction in polyunsaturated
      fatty acids. The product/precursor ratios for delta6 and delta5 desaturases, two
      key enzymes in the pathway leading to arachidonic acid, were significantly
      reduced in the group of patients. In the GLA group, a significant increase in the
      levels of dihomo-gamma-linolenic acid (20:3omega6) was observed in plasma and
      membranes, together with a parallel decrease in the 20:4/20:3omega6 ratio after
      supplementation. No significant changes were observed in the OA group. The levels
      of arachidonic acid did not change significantly in either group of patients.
      Platelet aggregation to collagen was unchanged in the GLA group, but
      significantly improved in the OA group. CONCLUSIONS: These results show that
      supplementation with precursors of arachidonic acid is ineffective in elevating
      plasma or membrane arachidonate levels and does not improve platelet aggregation,
      suggesting that synthesis of arachidonic acid through the delta5 desaturase
      cannot be correspondingly activated or that incorporation/retention of the
      produced fatty acid into lipids is impaired. The increased platelet aggregation
      in the OA group is likely to be explained by the effect of oleic acid contained
      in the diet, the effects of which may have been counteracted by the elevation in
      20:3omega6, a source of anti-aggregatory prostanoids, in the GLA group.

PMID- 9566836
TI  - Dietary nucleotides correct plasma and liver microsomal fatty acid alterations in
      rats with liver cirrhosis induced by oral intake of thioacetamide.
AB  - BACKGROUND/AIMS: Dietary nucleotides modulate a number of metabolic processes,
      including long-chain polyunsaturated fatty acid metabolism. In this study, we
      evaluated the effect of dietary nucleotides on plasma and liver microsomal fatty
      acid profiles in a rat model of liver cirrhosis induced by oral intake of
      thioacetamide. METHODS: Fifty-four female Wistar rats were assigned to one of the
      following groups: rats in the thioacetamide group (n=45) were given 300 mg
      thioacetamide/l in their drinking water for 4 months, and rats in the control
      group (n=9) received water during the same period. After 4 months of treatment, 9
      rats in each group were killed. The remaining rats in the thioacetamide group
      were divided into two new groups, and the animals in each were allowed to recover
      for 1 or 2 weeks on either a nucleotide-free diet or the same diet supplemented
      with 50 mg of each of the following: AMP, GMP, CMP, IMP and UMP per 100 g diet.
      RESULTS: Saturated (mainly stearic acid), monounsaturated, and n-6 long-chain
      polyunsaturated fatty acids (mainly arachidonic acid), and also the unsaturation
      index decreased in plasma of rats with experimental cirrhosis. Administration of
      the diet supplemented with nucleotides to thioacetamide-treated rats corrected
      plasma levels of saturated, n-6 long-chain polyunsaturated fatty acids and the
      unsaturation index. In liver microsomes, the cirrhotic rats showed lower levels
      of protein and higher levels of palmitic, oleic, linoleic and arachidonic acids.
      Protein concentrations and levels of all the above-mentioned fatty acids were
      corrected with the nucleotide-enriched diet. CONCLUSIONS: Dietary nucleotides
      contribute to correcting plasma and liver microsomal fatty acid alterations in
      rats with liver cirrhosis induced by chronic oral administration of
      thioacetamide.

PMID- 9566837
TI  - Protein kinase C alterations in aortic vascular smooth muscle cells from rats
      with cirrhosis.
AB  - BACKGROUND/AIMS: Alterations in signal transduction in vascular smooth muscle
      cells may contribute to vascular hyporeactivity in cirrhosis. Protein kinase C
      plays a role in vascular cell contraction by modifying contractile proteins and
      intracellular [Ca2+] homeostasis. The aim of this study was to examine the
      vascular reactivity and expression of protein kinase Calpha in aortae from rats
      with cirrhosis. METHODS: The contractile response to phorbol ester, a protein
      kinase C activator, was evaluated in endothelium-denuded aortic rings from normal
      and cirrhotic rats. Protein kinase Calpha expression was determined by Western
      blot analysis. RESULTS: Maximal contraction was significantly less marked in
      cirrhotic (1.24+/-0.24 g) than in control (3.43+/-0.27 g) aortae. Phorbol
      myristate-acetate-induced contraction was dependent on extracellular [Ca2+]
      concentrations, as shown by a reduction in maximal contraction when control and
      cirrhotic aortic rings were exposed to a Ca2+-free medium. Increasing the
      intracellular [Ca2+], by incubation with a Ca2+ ionophore, significantly
      increased the maximal contraction induced by phorbol myristate-acetate in
      cirrhotic but not in control rat aortae. Protein kinase Calpha expression was
      significantly lower in aortae in cirrhotic than in control rats. CONCLUSION:
      These results confirm alterations in protein kinase C in aortae from cirrhotic
      rats.

PMID- 9566838
TI  - Dedifferentiation of human hepatocytes by extracellular matrix proteins in vitro:
      quantitative and qualitative investigation of cytokeratin 7, 8, 18, 19 and
      vimentin filaments.
AB  - BACKGROUND/AIMS: Liver cirrhosis and carcinogenesis are accompanied by an
      alteration in extracellular matrix material. Histological studies reveal
      upregulation of the intermediate filaments cytokeratins 8 and 18 and de novo
      synthesis of vimentin, and cytokeratin 7 or 19 in hepatocytes. The aim of this
      study was to investigate how these two processes are linked. METHODS: Human
      hepatocytes were seeded: (i) on the matrix components collagen I, IV, laminin, or
      fibronectin; (ii) on stoichiometrically different complete matrices, derived from
      human placenta (matrix I) or the Englebreth-Holm-Swarm tumor (matrix II), and
      (iii) inside a three-dimensional collagen I sandwich. Filament expression and
      assembly were measured by cytofluor analysis or confocal laserscan microscopy.
      RESULTS: The matrix components or complete matrices triggered enhancement of
      cytokeratins 8 and 18 and de novo synthesis of cytokeratins 7, 19 and vimentin in
      a characteristic way. Confocal images demonstrated a dense and uniform network of
      cytokeratin 18 in freshly isolated cells, which was "replaced" by a few, thick
      protein bundles within 20 days. Interestingly, newly synthesized cytokeratin 19
      structurally resembled the cytokeratin 19 organization in biliary epithelial
      cells. Marked cytokeratin alterations could be partially prevented when
      hepatocytes were grown in a three-dimensional collagen sandwich. CONCLUSIONS:
      Pathological alterations to the chemical composition, molecular structure, or
      spatial arrangement of the liver matrix lead to specific changes in the
      intermediate filament pattern in human hepatocytes. We assume that degradation of
      the matrix results in pathological alterations to the hepatocyte-receptor matrix
      ligand ratio, followed by a switch from physiological to pathological cell
      activation.

PMID- 9566839
TI  - Laminin isoforms in non-tumoral and tumoral human livers. Expression of alpha1,
      alpha2, beta1, beta2 and gamma1 chain mRNA and an alpha chain homologous to the
      alpha2 chain.
AB  - BACKGROUND/AIMS: Laminins, the major non-collagenous basement membrane
      components, are involved in various biological processes. Laminin isoforms have
      never been characterized in human livers. The expression of five laminin mRNA was
      investigated in livers with or without cancer and in hepatoma cells and, by
      comparison, in both rat hepatoma and hepatic stellate cells. METHODS: Laminin
      alpha1, alpha2, beta1, beta2 and gamma1 mRNA was detected by northern blot and/or
      RT-PCR in livers without chronic disease (n=5), in both tumoral and non-tumoral
      areas of livers with hepatocellular carcinomas (n=13) or metastases (n=18), in
      human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic
      stellate cell cultures. RESULTS: Laminin alpha1, alpha2 and beta1 mRNA were found
      in 25-33% and gamma1 mRNA in 58% of the livers, the signal for laminin beta2 mRNA
      being faint in all the samples. Laminin alpha2, beta1, beta2 and gamma1 mRNA were
      expressed in hepatoma and stellate cells. The laminin alpha2 cDNA probe
      recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated
      oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells
      revealed 90% identity with the alpha2 chain sequence. Antibodies against peptide
      deduced from the conserved C-terminal domain of both alpha1 and alpha2 chains
      recognized polypeptides corresponding to the degradation products of alpha2 chain
      in liver extracts and both media and cell layers from hepatoma and stellate
      cells. In addition, a Mr=130000 polypeptide was revealed by these antibodies in
      liver extracts and cell layers, which was consistent with the expected size
      deduced from the 3.5 kb mRNA. CONCLUSIONS: This first report on laminin isoforms
      in human livers indicates that laminin 1 (alpha1-beta1-gamma1), 2 (alpha2-beta1
      gamma1), 3 (alpha1-beta2-gamma1) and 4 (alpha2-beta2-gamma1) mRNA and a
      polypeptide homologous to the alpha2 isoform, which could correspond to a
      truncated form of this chain, are usually expressed in non-tumoral and/or tumoral
      livers.

PMID- 9566840
TI  - Putrescine decreases cytochrome P450 3A4 levels during liver regeneration in the
      rat.
AB  - BACKGROUND/AIMS: The mechanism by which many cytochrome P450 (CYP) isozymes
      decrease during liver regeneration is unclear. Peptides and growth factors are
      thought to be involved. Putrescine, the first polyamine synthesised by ornithine
      decarboxylase, peaks early following partial hepatectomy and is known to play an
      essential role in hepatic regeneration. Gamma amino butyric acid was reported as
      a physiologic inhibitor of ornithine decarboxylase. In this work we studied the
      possible involvement of putrescine in the CYP reduction during liver
      regeneration. METHODS: Hepatectomised, putrescine-treated sham, and GABA-treated
      hepatectomised rats were used throughout. Total hepatic cytochrome P450, o
      dealkylase activities (CYP1A1 and CYP2B1/2), nifedipine oxidase activity
      (CYP3A4), and Western blot assays of their respective apoproteins were analysed
      in liver microsomes. Putrescine levels in hepatic tissue were also measured.
      RESULTS: Partial hepatectomy and putrescine treatment induced a significant
      diminution in total CYP (50% and 30% of sham-operated rats, respectively). Gamma
      amino butyric acid treatment prevented this decrease in partially hepatectomised
      rats. Nifedipine oxidase activity of partially hepatectomised and putrescine
      treated rats significantly decreased to 43% and 60% of that in sham-operated
      rats, respectively. Again, gamma amino butyric acid prevented the diminution in
      partially hepatectomised rats. No significant changes were observed in o
      dealkylase activities. CONCLUSIONS: These results show that inducible CYP1A1 and
      CYP2B1/2, which are important in carcinogen metabolisation, are preserved after
      partial hepatectomy. However, constitutive CYP3A4, which represents 50% of total
      CYP and metabolises drugs like nifedipine, warfarin, acetaminophen, cyclosporin
      and FK-506, is reduced during liver regeneration. Our experiments suggest that
      endogenous putrescine is, at least, partly responsible for this decrease.

PMID- 9566841
TI  - Nonparenchymal cells in chronically hyperinsulinemic liver acini of diabetic
      rats, with special regard to hepatic stellate cells.
AB  - BACKGROUND/AIMS: An increase in proliferative activity and other distinct
      hepatocellular alterations--resembling preneoplastic foci and progressing to
      hepatocellular tumors--have been shown to develop in liver acini draining the
      blood from islets of Langerhans, transplanted through the portal vein into the
      liver of streptozotocin-diabetic rats. METHODS: Altered and unaltered liver acini
      were investigated for possible changes in hepatic stellate cells 4-76 days after
      islet transplantation. RESULTS: Corresponding to a significant increase in the
      hepatocellular volume, the volume density of total nonparenchymal cells was
      significantly reduced in altered compared to unaltered liver acini. With regard
      to the total nonparenchymal cell volume, the hepatic stellate cell fraction was
      not different, whereas the fraction of Kupffer cells was significantly reduced
      and the fraction of sinusoidal endothelial cells was significantly increased in
      altered compared to unaltered liver acini, respectively. The volume density as
      well as the single volume of the hepatic stellate cell mitochondria increased
      significantly in altered compared to unaltered liver acini. Hepatic stellate cell
      lipid droplets did not show significant differences between altered and unaltered
      liver acini. In situ hybridization for hepatocyte growth factor mRNA showed no
      differences in intensity of the specific signals in hepatic stellate cells of
      altered versus unaltered liver acini. The transplanted islets were negative for
      hepatic growth factor mRNA. CONCLUSIONS: The results suggest that hepatic growth
      factor production by hepatic stellate cells or by islet cells is not relevant to
      hepatocellular proliferative activity in altered liver acini.

PMID- 9566842
TI  - Intrahepatic cholangiocarcinoma arising in congenital hepatic fibrosis: report of
      an autopsy case.
AB  - We report an autopsy case of a 60-year-old woman who had congenital hepatic
      fibrosis with intrahepatic cholangiocarcinoma. A white nodular lesion with a
      surrounding vague gray area was detected in the right lobe of the liver.
      Microscopically, most of the nodular lesion was a poorly-differentiated
      adenocarcinoma. In the surrounding gray area, small bile ducts and bile ductules
      showed prominent epithelial overgrowth, some of which was composed of dysplasia
      and well-differentiated adenocarcinoma. The background liver showed the
      characteristic features of congenital hepatic fibrosis. Immunohistochemically,
      biliary oncofetal markers (mucin core protein 1 and carcinoembryonic antigen)
      were more frequently and extensively expressed in poorly-differentiated than well
      differentiated adenocarcinoma. This is the 4th reported case of intrahepatic
      cholangiocarcinoma arising in congenital hepatic fibrosis and suggests that
      malignant transformation via dysplasia occurs in the abnormal intrahepatic
      biliary tree of older congenital hepatic fibrosis patients.

PMID- 9566843
TI  - Post-traumatic membranous obstruction of the inferior vena cava associated with a
      hypercoagulable state.
AB  - It has been hypothesized that abdominal trauma may be one of the factors involved
      in membranous obstruction of the inferior vena cava. We present two cases of
      membranous obstruction of the inferior vena cava associated with trauma. One
      asymptomatic case, associated with an occult myeloproliferative disorder,
      developed within 3 years of a violent abdominal trauma. The other case,
      associated with familial plasminogen deficiency, was discovered at surgery 3 days
      after a road accident with obvious abdominal trauma, since superimposed extensive
      thrombosis of the inferior vena cava caused acute Budd-Chiari syndrome. We
      conclude that underlying prothrombotic conditions are probably necessary for the
      development of membranous obstruction of the inferior vena cava and that minor
      trauma may contribute to the development of thrombosis through indirect
      mechanisms.

PMID- 9566844
TI  - Images in hepatology: bile acid-induced diarrhea due to a choledochocolic
      fistula.

PMID- 9566845
TI  - Alcohol, HCV infection, and liver cirrhosis: is the cup half full or half empty?

PMID- 9566846
TI  - "Negative trials" are positive!

PMID- 9566847
TI  - Wilson's disease: the scourge of copper.

PMID- 9566848
TI  - Prevalence of the haemochromatosis gene mutation in non-cirrhotic liver with
      hepatocellular carcinoma.

PMID- 9566849
TI  - "P-glycoproteins are not released into bile".

PMID- 9566850
TI  - Insulin antagonism: a novel role for human serum transferrin.
AB  - We have purified alpha2-glycoprotein (alpha2-GP), an insulin antagonist from
      human plasma which is induced by growth hormone (GH), and shown that pure alpha2
      GP is a potent antagonist of severe insulin-induced hypoglycemia, producing acute
      hyperglycemia in intact rats and ketonuria in diabetic rats. The N-terminal amino
      acid sequence of alpha2-GP and the reactivity of alpha2-GP with an
      antitransferrin monoclonal antibody show that alpha2-GP is identical to human
      serum transferrin. Furthermore, pure human serum transferrin and non-glycosylated
      recombinant human transferrin reproduce the insulin antagonist effects of alpha2
      GP in rats, whereas ovotransferrin shows no such effect. The neutralization of
      the insulin antagonism of human serum transferrin by an anti-transferrin
      monoclonal antibody shows that transferrin has a new function as a potent insulin
      antagonist. This novel role for human serum transferrin in the regulation of
      glucose metabolism provides a reasonable mechanism for the diabetogenic effect of
      GH, and has important implications for the etiology and progression of diabetes.

PMID- 9566851
TI  - Epinephrine-induced reduction in insulin receptor mRNA level and stability in U
      937 human promonocytic cells.
AB  - The administration of 10(-5) M epinephrine transiently decreased insulin receptor
      (IR) mRNA levels in U-937 human promonocytic cells, which reached their minimum
      value after 24 hours. Such a decrease seems to be due, at least in part, to a
      reduction in transcript stability, since the IR mRNA half-life was observed to
      decline from approximately 4h in untreated cells to 3 h in epinephrine-treated
      cells. Computer inspection of the sequence of the 3' untranslated region of the
      human IR mRNA showed nine AUUUA pentamers and three U-rich regions. These domains
      could be targets for a RNA-binding protein induced by treatment with epinephrine
      producing a destabilization of IR mRNA in U-937 cells.

PMID- 9566852
TI  - The long acting human insulin analog HOE 901: characteristics of insulin
      signalling in comparison to Asp(B10) and regular insulin.
AB  - HOE 901 is a new biosynthetic long-acting human insulin analog
      (GLY[A21]ARG[B31]ARG[B32]). We compared HOE 901 with normal human insulin and the
      insulin analog Asp(B10), which is known to have increased mitogenic activity at
      least partially mediated through the insulin receptor. We have analyzed receptor
      binding, insulin-induced receptor autophosphorylation and phosphorylation of
      receptor substrates in rat-1 fibroblasts overexpressing human insulin receptor
      isoform A (HIR A) or B (HIR B). In HIR A expressing cells, insulin and its
      analogs showed no significant differences in receptor association while clearly
      different dissociation kinetics were observed. In HIR B expressing cells, no
      significant differences in association and dissociation kinetics were observed.
      All insulins induced rapid autophosphorylation of the insulin receptor reaching a
      maximum after 10 min of stimulation. Asp(B10)insulin induced a prolonged
      phosphorylation state (over 60 minutes) of the 95 kDa receptor beta-subunit and
      of the substrates IRS-1/IRS-2 and Shc in contrast to normal human insulin and to
      HOE 901. In addition, we observed an increased and prolonged tyrosine
      phosphorylation of an unidentified protein with Asp(B10)insulin at about 60 kDa.
      Insulin-dependent dephosphorylation of the focal adhesion kinase (p125FAK) was
      equally induced by all these ligands. With respect to [3H]thymidine incorporation
      into DNA, HOE 901 had similar effects as normal human insulin, while
      Asp(B10)insulin showed increased [3H]thymidine incorporation. In summary, the
      data show that the increased mitogenic activity of Asp(B10)insulin may be
      explained with a prolonged kinetics of tyrosine phosphorylation of the insulin
      receptor and of insulin signalling elements together with the preferential
      phosphorylation of an yet unidentified 60 kDa protein. HOE 901 behaves with
      respect to insulin receptor binding, receptor autophosphorylation,
      phosphorylation of signalling elements and promotion of mitogenesis like regular
      human insulin.

PMID- 9566853
TI  - Unspecific binding capacity of androgen receptors in the rat uterus.
AB  - Rat uterine cytosol receptor homogenate binds estradiol and testosterone alike.
      Saturation and displacement studies were done with these two hormones.
      Testosterone displaced only testosterone while estradiol displaced estradiol as
      well as testosterone. The experiments call attention to the unspecific binding
      capacity of rat uterine androgen receptors.

PMID- 9566854
TI  - Secretion of major adrenal androgens following ACTH administration in obese women
      with different body fat distribution.
AB  - To investigate whether obese female subjects with abdominal obesity may have
      adrenal androgen hypersecretion, we examined two groups of women with abdominal
      (n = 12) and peripheral (n = 13) obesity (defined by body mass index and waist-to
      hip ratio) and a group of seven healthy normal-weight women. All subjects
      underwent the following protocol study that included a) baseline determination of
      major adrenal androgens, b) an ACTH test, performed by administering two boli of
      ACTH (Synacthen, 0.2 microg/Kg BW, e.v.), at 90 min intervals, with blood samples
      taken for cortisol and androgens, c) an oral glucose tolerance test, performed by
      administering glucose (75 gr), with blood samples taken for glucose and insulin
      determination. Each woman also underwent a control saline study. We then
      investigated the relationships between basal and stimulated androgen levels, body
      weight and fat distribution and fasting and stimulated insulin levels. Although
      basal cortisol levels were similar, their increase (as AUC) after the ACTH test
      was higher in women with abdominal obesity than in the other groups. On the
      contrary, there were no significant differences in basal and stimulated serum
      levels of dehydroepiandrosterone, androstenedione and 17-hydroxyprogesterone
      among the three groups. Fasting and stimulated (as AUC) insulin levels were
      significantly higher (p < 0.05) in women with abdominal obesity than in those
      with peripheral obesity and controls. No significant correlation was present
      between basal and stimulated androgen levels and body mass index, the waist-to
      hip ratio or basal and stimulated cortisol values. Therefore, our data indicate
      that adrenal androgen secretion following low-dose ACTH administration in
      premenopausal women does not seem to be a function of body fat mass, fat
      distribution and insulin levels, nor does it correlate with the capacity of the
      adrenal glands to secrete cortisol in both basal and stimulated conditions.

PMID- 9566855
TI  - The relation between plasma lipid levels and pseudocholinesterase activity in
      hypothyroidism.
AB  - The relation of plasma lipids and pseudocholinesterase (PChE) activity was
      studied in rats made hypothyroid by treatment with propylthiouracil (0.05% in
      drinking water for 28 days) and in hypothyroid patients prior and after L
      thyroxine-therapy (1. week 25-50 microg, 2.-4. week 100 microg daily). In rats,
      thyroid hormone deficiency caused a significant increase in plasma and adipose
      tissue PChE activity as well as total plasma cholesterol (TC) concentration, and
      a decrease in plasma triglyceride (TG) concentration. In contrast to rats,
      thyroid-deficient humans demonstrated a decrease in plasma PChE activity and an
      increase in both TC and TG, in comparison with euthyroid controls. After one
      month's therapy with L-thyroxine, reversion of PChE activity and lipid
      concentrations occurred. The opposite changes of PChE elicited by thyroid hormone
      deficiency in men and rats are similar to the respective changes in lipoprotein
      lipase (LPL) activity, observed by other authors. The inverse correlation between
      both PChE and LPL activity and TG concentration suggests that PChE, similarly to
      LPL, may be involved in TG hydrolysis.

PMID- 9566856
TI  - Body fat distribution, insulin mediated suppression of non-esterified fatty acids
      and plasma triglycerides in obese subjects.
AB  - Triglyceride levels and free fatty acid metabolism are influenced by body fat
      distribution. To test whether the pattern of fat distribution in obese subjects
      results in distinct insulin mediated suppression of non-esterified fatty acids
      which could account for differences in plasma triglycerides, we studied 59 obese
      subjects who were classified according to waist-to-hip ratio. Non-esterified
      fatty acids and insulin response to a 75 g oral glucose tolerance test were
      higher in abdominal obesity. Total non-esterified fatty acids response, after
      adjustment for sex, showed a positive association with waist-to hip ratio (r =
      0.292; p < 0.05). The abdominal obese group had higher fasting triglycerides
      (1.74+/-0.83 versus 1.11+/-0.71 mmol/L; p = 0.003) and lower glucose/insulin
      ratio (5.2+/-2.3 versus 7.1+/-2.4; p = 0.003). Stepwise multiple regression
      analysis showed that triglyceride levels are explained by fasting and 120 min non
      esterified fatty acids and by glucose/insulin ratio. We conclude that abdominal
      obesity is associated with a higher resistance to insulin mediated suppression of
      non-esterified fatty acids in obese subjects. Variation of triglyceride
      concentrations in obesity is dependent on both fasting and 120 min non-esterified
      fatty acids as well as on insulin sensitivity to glucose utilization.

PMID- 9566857
TI  - Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the
      possible role of oxidative stress.
AB  - ICAM-1 is one of the most important intercellular adhesion molecules involved in
      atherogenesis. Previous studies reported increased circulating ICAM-1 plasma
      levels in NIDDM patients with or without vascular complications. It has been
      suggested that an acute increase of plasma glucose may produce an oxidative
      stress in man, and in vitro studies have demonstrated that high glucose and free
      radicals induce cellular expression of ICAM-1. In this study, three different
      experiments were performed in nine NIDDM patients and in seven matched healthy
      controls: oral glucose tolerance test, antioxidant glutathione i.v.
      administration for two h, oral glucose tolerance test plus glutathione i.v.
      administration. Blood samples were drawn at -15 min and every 30 min from 0 to
      180 min. During the oral glucose tolerance test, circulating ICAM-1 plasma levels
      significantly increased in both diabetic and normal subjects. Glutathione
      administration during the oral glucose tolerance test abolished this phenomenon.
      Glutathione administered alone significantly decreased circulating ICAM-1 plasma
      levels in diabetic patients, while no effect was observed in the normal subjects.
      These data suggest that hyperglycemia may induce an increase of circulating ICAM
      1 plasma levels through an oxidative stress, and that the antioxidant glutathione
      counterbalances this effect. These data support the hypothesis of a causal
      relationship linking hyperglycemia, oxidative stress and atherogenesis in
      diabetes mellitus.

PMID- 9566858
TI  - Vanadyl treatment normalizes submandibular salivary gland insulin-like
      immunoreactivity in streptozotocin-diabetic rats.
AB  - Rat submandibular salivary glands (SSG) contain a compound displaying insulin
      like immunoreactivity (ILI) and various biological activities of insulin. As SSG
      ILI levels were reported to be increased in streptozotocin (STZ)-induced diabetes
      but not normalized by a two-week insulin treatment, we decided to check whether
      another antidiabetic treatment, vanadyl sulphate (VOSO4), was able to regulate
      SSG ILI concentration. A short term (8 days) i.p. VOSO4 treatment (total dose =
      1.3 mmol/kg) of rats made diabetic 8 days earlier by a single i.v. injection of
      STZ (60 mg/kg BW) was able to induce a long-term (4 weeks) correction of
      hyperglycemia while weight gain was re-established. In untreated diabetic animals
      (approximately -25%) and increased (approximately +175%) as compared to normal
      rats. Both parameters were normalized in VOSO4-treated diabetic rats.

PMID- 9566859
TI  - Insulin resistance, dehydroepiandrosterone sulfate and sex hormone-binding
      globulin in essential hypertension.
AB  - OBJECTIVE: To evaluate insulin sensitivity, and serum levels of sex hormone
      binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEA-sulfate), in
      patients with essential hypertension. DESIGN AND METHODS: In 15 non-treated
      hypertensive patients, insulin resistance was measured by an insulin suppression
      test (IST). Serum levels of DHEA-sulfate and SHBG were measured at the beginning
      and at the end of the IST. The results were compared to those of a control group
      of 10 healthy normotensive subjects matched for age, sex and body mass index
      (BMI).

PMID- 9566860
TI  - Significance of tumor necrosis factor alpha in patients with long-standing type-I
      diabetes mellitus.
AB  - Fifteen out of the forty-five patients with long-standing diabetes mellitus type
      I were characterised by the presence of TNFalpha in the sera when examined on
      several occasions over a period of five years. TNFalpha-producing patients had a
      better control of the disease and a smaller percentage of them suffered from
      diabetic complications as compared with those not producing this cytokine.
      TNFalpha-producing patients had lower levels of the proinflammatory markers - IL6
      and CRP, and higher concentrations of ACTH and cortisol than those not producing
      this cytokine. We suggest that TNFalpha released systemically in diabetic
      patients stimulates the hypophysis-adrenal axis, and in that way indirectly
      ameliorates autoimmune response occurring during the advanced phase of the
      disease.

PMID- 9566861
TI  - Application of a bioassay with CHO cells for the routine detection of stimulating
      and blocking autoantibodies to the TSH-receptor.
AB  - The importance of bioassays measuring stimulating and blocking autoantibodies to
      the TSH-receptor (TSH-R) by their effect on cAMP production in CHO cells
      transfected with the recombinant TSH-R is increasingly recognized. The standard
      technique for this bioassay is cumbersome, as it involves purification of serum
      IgG with polyethylene glycol (PEG) and resuspension in hypotonic buffer. We have
      therefore established a simpler approach for the detection of stimulating and
      blocking autoantibodies using JP09 CHO cells and unfractionated human serum. The
      cAMP concentration was measured by a highly sensitive commercial radioimmuno
      assay. Thyroid stimulating autoantibodies (TSAb) were present in 107 out of 126
      patients with Graves' disease (85%) and in 4 out of 40 patients with Hashimoto's
      thyroiditis (10%). Specificity was confirmed by the fact that only 1 patient with
      insulin dependent diabetes mellitus (IDDM) out of 64 patients with different non
      thyroid autoimmune disorders (46 with IDDM, 10 with stiff man syndrome and 8 with
      rheumatoid arthritis) and 2 out of 100 healthy controls (2%) were positive in
      this assay. In the subgroup of hyperthyroid Graves' disease patients 76 out of 83
      (92%) had TSAb and the same number had TSH binding inhibiting immunoglobulin
      (TBII), as assessed by the commercial TRAK assay. Although both antibody types
      showed only a weak correlation (r = 0.30), a combination of TSAb and TBII
      detected 98% of all Graves' patients and 99% of the hyperthyroid subgroup.
      Thyroid blocking autoantibodies (TBAb) were measured in 4 out of 24 TSAb negative
      patients with Graves' disease (17%), who were hypothyroid and positive for TBII.
      A comparison of our bioassay with the standard bioassay using PEG precipitation
      showed a good correlation (r = 0.76,p < 0.001), demonstrating the feasibility of
      the simplified assay for the routine detection of TSAb and TBAb in Graves'
      disease.

PMID- 9566862
TI  - Insulinotropic action of 6-O-acyl-D-glucose esters.
AB  - Several 6-O-acyl-D-glucose esters were examined for their possible insulinotropic
      action in rats islets incubated for 90 minutes in the absence or presence of
      either D-glucose or L-leucine. As a rule, 6-O-acetyl-D-glucose and either medium-
      and long-chain acyl-D-glucose esters only exerted modest effects upon insulin
      release, much less pronounced than those previously recorded with hexose
      pentaacetate esters. Nevertheless, under suitable experimental conditions, 6-O
      octanoyl-D-glucose and 6-O-decanoyl-D-glucose significantly augmented insulin
      output, suggesting that such esters could be used, instead of D-glucose itself,
      as cell nutrients.

PMID- 9566863
TI  - Serum leptin concentration increase during luteal phase in healthy premenopausal
      women.

PMID- 9566864
TI  - Double-stranded RNA-independent dimerization of interferon-induced protein kinase
      PKR and inhibition of dimerization by the cellular P58IPK inhibitor.
AB  - The interferon (IFN)-induced, double-stranded RNA-activated protein kinase (PKR)
      mediates the antiviral and antiproliferative actions of IFN, in part, via its
      translational inhibitory properties. Previous studies have demonstrated that PKR
      forms dimers and that dimerization is likely to be required for activation and/or
      function. In the present study we used multiple approaches to examine the
      modulation of PKR dimerization. Deletion analysis with the lambda repressor
      fusion system identified a previously unrecognized site involved in PKR
      dimerization. This site comprised amino acids (aa) 244 to 296, which span part of
      the third basic region of PKR and the catalytic subdomains I and II. Using the
      yeast two-hybrid system and far-Western analysis, we verified the importance of
      this region for dimerization. Furthermore, coexpression of the 52-aa region alone
      inhibited the formation of full-length PKR dimers in the lambda repressor fusion
      and two-hybrid systems. Importantly, coexpression of aa 244 to 296 exerted a
      dominant-negative effect on wild-type kinase activity in a functional assay. Due
      to its role as a mediator of IFN-induced antiviral resistance, PKR is a target of
      viral and cellular inhibitors. Curiously, PKR aa 244 to 296 contain the binding
      site for a select group of specific inhibitors, including the cellular protein
      P58IPK. We demonstrated, utilizing both the yeast and lambda systems, that
      P58IPK, a member of the tetratricopeptide repeat protein family, can block kinase
      activity by preventing PKR dimerization. In contrast, a nonfunctional form of
      P58IPK lacking a TPR motif did not inhibit kinase activity or perturb PKR dimers.
      These results highlight a potential mechanism of PKR inhibition and define a
      novel class of PKR inhibitors. Finally, the data document the first known example
      of inhibition of protein kinase dimerization by a cellular protein inhibitor. On
      the basis of these results we propose a model for the regulation of PKR
      dimerization.

PMID- 9566865
TI  - Intrinsic transcriptional activation-inhibition domains of the polyomavirus
      enhancer binding protein 2/core binding factor alpha subunit revealed in the
      presence of the beta subunit.
AB  - A member of the polyomavirus enhancer binding protein 2/core binding factor
      (PEBP2/CBF) is composed of PEBP2 alphaB1/AML1 (as the alpha subunit) and a beta
      subunit. It plays an essential role in definitive hematopoiesis and is frequently
      involved in the chromosomal abnormalities associated with leukemia. In the
      present study, we report functionally separable modular structures in PEBP2
      alphaB1 for DNA binding and for transcriptional activation. DNA binding through
      the Runt domain of PEBP2 alphaB1 was hindered by the adjacent carboxy-terminal
      region, and this inhibition was relieved by interaction with the beta subunit.
      Utilizing a reporter assay system in which both the alpha and beta subunits are
      required to achieve strong transactivation, we uncovered the presence of
      transcriptional activation and inhibitory domains in PEBP2 alphaB1 that were only
      apparent in the presence of the beta subunit. The inhibitory domain keeps the
      full transactivation potential of full-length PEBP2 alphaB1 below its maximum
      potential. Fusion of the transactivation domain of PEBP2 alphaB1 to the yeast
      GAL4 DNA-binding domain conferred transactivation potential, but further addition
      of the inhibitory domain diminished the activity. These results suggest that the
      activity of the alpha subunit as a transcriptional activator is regulated
      intramolecularly as well as by the beta subunit. PEBP2 alphaB1 and the beta
      subunit were targeted to the nuclear matrix via signals distinct from the nuclear
      localization signal. Moreover, the transactivation domain by itself was capable
      of associating with the nuclear matrix, which implies the existence of a
      relationship between transactivation and nuclear matrix attachment.

PMID- 9566866
TI  - Chromatin remodeling mediated by Drosophila GAGA factor and ISWI activates fushi
      tarazu gene transcription in vitro.
AB  - GAGA factor is known to remodel the chromatin structure in concert with
      nucleosome-remodeling factor NURF in a Drosophila embryonic S150 extract. The
      promoter region of the Drosophila fushi tarazu (ftz) gene carries several binding
      sites for GAGA factor. Both the GAGA factor-binding sites and GAGA factor per se
      are necessary for the proper expression of ftz in vivo. We observed
      transcriptional activation of the ftz gene when a preassembled chromatin template
      was incubated with GAGA factor and the S150 extract. The chromatin structure
      within the ftz promoter was specifically disrupted by incubation of the
      preassembled chromatin with GAGA factor and the S150 extract. Both
      transcriptional activation and chromatin disruption were blocked by an antiserum
      raised against ISWI or by base substitutions in the GAGA factor-binding sites in
      the ftz promoter region. These results demonstrate that GAGA factor- and ISWI
      mediated disruption of the chromatin structure within the promoter region of ftz
      activates transcription on the chromatin template.

PMID- 9566867
TI  - The Gfi-1B proto-oncoprotein represses p21WAF1 and inhibits myeloid cell
      differentiation.
AB  - Gfi-1 is a cellular proto-oncogene that was identified as a target of provirus
      integration in T-cell lymphoma lines selected for interleukin-2 (IL-2)
      independence in culture and in primary retrovirus-induced lymphomas. Gfi-1
      encodes a zinc finger protein that functions as a transcriptional repressor. Here
      we show that Gfi-1B, a Gfi-1 related gene expressed in bone marrow and spleen,
      also encodes a transcriptional repressor. IL-6-induced G1 arrest and
      differentiation of the myelomonocytic cell line M1 were linked to the
      downregulation of Gfi-1B and the parallel induction of the cyclin-dependent
      kinase inhibitor p21WAF1. Experiments addressing the potential mechanism of the
      apparent coordinate regulation of these genes revealed that Gfi-1B represses
      p21WAF1 directly by binding to a high-affinity site at -1518 to -1530 in the
      p21WAF1 promoter. Forced expression of Gfi-1B, but not of Gfi-1B deletion mutants
      lacking the repressor domain, blocked the IL-6-mediated induction of p21WAF1 and
      inhibited G1 arrest and differentiation. We conclude that Gfi-1B is a direct
      repressor of the p21WAF1 promoter, the first such repressor identified to date,
      and that sustained expression of Gfi-1B blocks IL-6-induced G1 arrest and
      differentiation of M1 cells perhaps because it prevents p21WAF1 induction by IL
      6.

PMID- 9566868
TI  - Wnt-1 induces growth, cytosolic beta-catenin, and Tcf/Lef transcriptional
      activation in Rat-1 fibroblasts.
AB  - Genetic evidence suggests that regulation of beta-catenin and regulation of
      Tcf/Lef family transcription factors are downstream events of the Wnt signal
      transduction pathway. However, a direct link between Wnt activity and Tcf/Lef
      transcriptional activation has yet to be established. In this study, we show that
      Wnt-1 induces a growth response in a cultured mammalian cell line, Rat-1
      fibroblasts. Wnt-1 induces serum-independent cellular proliferation of Rat-1
      fibroblasts and changes in morphology. Rat-1 cells stably expressing Wnt-1 (Rat
      1/Wnt-1) show a constitutive up-regulation of cytosolic beta-catenin, while
      membrane-associated beta-catenin remains unaffected. Induction of cytosolic beta
      catenin in Rat-1/Wnt-1 cells is correlated with activation of a Tcf-responsive
      transcriptional element. We thus provide evidence that Wnt-1 induces Tcf/Lef
      transcriptional activation in a mammalian system. Expression of a mutant beta
      catenin (beta-CatS37A) in Rat-1 cells does not result in a proliferative response
      or a detectable change in the cytosolic beta-catenin protein level. However, beta
      CatS37A expression in Rat-1 cells results in strong Tcf/Lef transcriptional
      activation, comparable to that seen in Wnt-1-expressing cells. These results
      suggest that Wnt-1 induction of cytosolic beta-catenin may have functions in
      addition to Tcf/Lef transcriptional activation.

PMID- 9566869
TI  - Activation of the small GTPase Ral in platelets.
AB  - Ral is a ubiquitously expressed Ras-like small GTPase which is abundantly present
      in human platelets. The biological function of Ral and the signaling pathway in
      which Ral is involved are largely unknown. Here we describe a novel method to
      measure Ral activation utilizing the Ral binding domain of the putative Ral
      effector RLIP76 as an activation-specific probe. With this assay we investigated
      the signaling pathway that leads to Ral activation in human platelets. We found
      that Ral is rapidly activated after stimulation with various platelet agonists,
      including alpha-thrombin. In contrast, the platelet antagonist prostaglandin I2
      inhibited alpha-thrombin-induced Ral activation. Activation of Ral by alpha
      thrombin could be inhibited by depletion of intracellular Ca2+, whereas the
      induction of intracellular Ca2+ resulted in the activation of Ral. Our results
      show that Ral can be activated by extracellular stimuli. Furthermore, we show
      that increased levels of intracellular Ca2+ are sufficient for Ral activation in
      platelets. This activation mechanism correlates with the activation mechanism of
      the small GTPase Rap1, a putative upstream regulator of Ral guanine nucleotide
      exchange factors.

PMID- 9566870
TI  - Regulation of cell size by glucose is exerted via repression of the CLN1
      promoter.
AB  - Yeast cells are keenly sensitive to the availability and quality of nutrients.
      Addition of glucose to cells growing on a poorer carbon source elicits a cell
      cycle delay during G1 phase and a concomitant increase in the cell size. The
      signal is transduced through the RAS-cyclic AMP pathway. Using synchronized
      populations of G1 cells, we show that the increase in cell size required for
      budding depends upon CLN1 but not other G1 cyclins. This delay in cell cycle
      initiation is associated specifically with transcriptional repression of CLN1.
      CLN2 is not repressed. Repression of CLN1 is not limited to the first cycle
      following glucose addition but occurs in each cell cycle during growth on
      glucose. A 106-bp fragment of the CLN1 promoter containing the three MluI cell
      cycle box (MCB) core elements responsible for the majority of CLN1-associated
      upstream activation sequence activity is sufficient to confer glucose-induced
      repression on a heterologous reporter. A mutant CLN2 promoter that is rendered
      dependent upon its three MCB core elements due to inactivation of its Swi4
      dependent cell cycle box (SCB) elements is also repressed by glucose. The
      response to glucose is partially suppressed by inactivation of SWI4, but not
      MBP1, which is consistent with the dependence of MCB core elements upon the SCB
      binding transcription factor (SBF). We suggest that differential regulation of
      CLN1 and CLN2 by glucose results from differences in the capacity of SBF to
      activate transcription driven by SCB and MCB core elements. Finally, we show that
      transcriptional repression is sufficient to explain the cell cycle delay that
      occurs in response to glucose.

PMID- 9566871
TI  - Posttranslational regulation of Ty1 retrotransposition by mitogen-activated
      protein kinase Fus3.
AB  - Ty1 retrotransposons in Saccharomyces cerevisiae are maintained in a state of
      transpositional dormancy. We isolated a mutation, rtt100-1, that increases the
      transposition of genomic Ty1 elements 18- to 56-fold but has little effect on the
      transposition of related Ty2 elements. rtt100-1 was shown to be a null allele of
      the FUS3 gene, which encodes a haploid-specific mitogen-activated protein kinase.
      In fus3 mutants, the levels of Ty1 RNA, protein synthesis, and proteolytic
      processing were not altered relative to those in FUS3 strains but steady-state
      levels of TyA, integrase, and reverse transcriptase proteins and Ty1 cDNA were
      all increased. These findings suggest that Fus3 suppresses Ty1 transposition by
      destabilizing viruslike particle-associated proteins. The Fus3 kinase is
      activated through the mating-pheromone response pathway by phosphorylation at
      basal levels in naive cells and at enhanced levels in pheromone-treated cells. We
      demonstrate that suppression of Ty1 transposition in naive cells requires basal
      levels of Fus3 activation. Substitution of conserved amino acids required for
      activation of Fus3 derepressed Ty1 transposition. Moreover, epistasis analyses
      revealed that components of the pheromone response pathway that act upstream of
      Fus3, including Ste4, Ste5, Ste7, and Ste11, are required for the
      posttranslational suppression of Ty1 transposition by Fus3. The regulation of Ty1
      transposition by Fus3 provides a haploid-specific mechanism through which
      environmental signals can modulate the levels of retrotransposition.

PMID- 9566872
TI  - Nuclear localization of IkappaB alpha is mediated by the second ankyrin repeat:
      the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear
      import sequences.
AB  - The ability of the IkappaB alpha protein to sequester dimeric NF-kappaB/Rel
      proteins in the cytoplasm provides an effective mechanism for regulating the
      potent transcriptional activation properties of NF-kappaB/Rel family members.
      IkappaB alpha can also act in the nucleus as a postinduction repressor of NF
      kappaB/Rel proteins. The mechanism by which IkappaB alpha enters the nucleus is
      not known, as IkappaB alpha lacks a discernible classical nuclear localization
      sequence (NLS). We now report that nuclear localization of IkappaB alpha is
      mediated by a novel nuclear import sequence within the second ankyrin repeat.
      Deletion of the second ankyrin repeat or alanine substitution of hydrophobic
      residues within the second ankyrin repeat disrupts nuclear localization of
      IkappaB alpha. Furthermore, a region encompassing the second ankyrin repeat of
      IkappaB alpha is able to function as a discrete nuclear import sequence. The
      presence of a discrete nuclear import sequence in IkappaB alpha suggests that
      cytoplasmic sequestration of the NF-kappaB/Rel-IkappaB alpha complex is a
      consequence of the mutual masking of the NLS within NF-kappaB/Rel proteins and
      the import sequence within IkappaB alpha. Nuclear import may be a conserved
      property of ankyrin repeat domains (ARDs), as the ARDs from two other ARD
      containing proteins, 53BP2 and GABPbeta, are also able to function as nuclear
      import sequences. We propose that the IkappaB alpha ankyrin repeats define a
      novel class of cis-acting nuclear import sequences.

PMID- 9566873
TI  - Transcriptional activation of the integrated chromatin-associated human
      immunodeficiency virus type 1 promoter.
AB  - The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression
      involves a complex interplay between cellular transcription factors, chromatin
      associated proviral DNA, and the virus-encoded transactivator protein, Tat. Here
      we show that Tat transactivates the integrated HIV-1 long terminal repeat (LTR),
      even in the absence of detectable basal promoter activity, and this
      transcriptional activation is accompanied by chromatin remodeling downstream of
      the transcription initiation site, as monitored by increased accessibility to
      restriction endonucleases. However, with an integrated promoter lacking both Sp1
      and NF-kappaB sites, Tat was unable to either activate transcription or induce
      changes in chromatin structure even when it was tethered to the HIV-1 core
      promoter upstream of the TATA box. Tat responsiveness was observed only when Sp1
      or NF-kappaB was bound to the promoter, implying that Tat functions subsequent to
      the formation of a specific transcription initiation complex. Unlike Tat, NF
      kappaB failed to stimulate the integrated transcriptionally silent HIV-1
      promoter. Histone acetylation renders the inactive HIV-1 LTR responsive to NF
      kappaB, indicating that a suppressive chromatin structure must be remodeled prior
      to transcriptional activation by NF-kappaB. Taken together, these results suggest
      that Sp1 and NF-kappaB are required for the assembly of transcriptional complexes
      on the integrated viral promoter exhibiting a continuum of basal activities, all
      of which are fully responsive to Tat.

PMID- 9566874
TI  - Stat3 activation by Src induces specific gene regulation and is required for cell
      transformation.
AB  - While signal transducers and activators of transcription (STATs) were originally
      discovered as intracellular effectors of normal signaling by cytokines,
      increasing evidence also points to a role for STAT transcription factors in
      oncogenesis. Previous studies have demonstrated that one STAT family member,
      Stat3, possesses constitutively elevated tyrosine phosphorylation and DNA-binding
      activity in fibroblasts stably transformed by the Src oncoprotein. To determine
      if this Stat3 activation by Src could induce Stat3-mediated gene expression,
      luciferase reporter constructs based on synthetic and authentic promoters were
      transfected into NIH 3T3 cells. Activation of endogenous cellular Stat3 by the
      Src oncoprotein induced gene expression through a Stat3-specific binding element
      (TTCCCGAA) of the C-reactive protein gene promoter. A naturally occurring splice
      variant of human Stat3 protein, Stat3beta, with a deletion in the C-terminal
      transactivation domain abolished this gene induction in a dominant negative
      manner. Expression of Stat3beta did not have any effect on a reporter construct
      based on the c-fos serum response element, which is not dependent on Stat3
      signaling, indicating that Stat3beta does not nonspecifically inhibit other
      signaling pathways or Src function. Transfection of vectors expressing Stat3beta
      together with Src blocked cell transformation by Src as measured in a
      quantitative focus formation assay using NIH 3T3 cells. By contrast, Stat3beta
      had a much less pronounced effect on focus formation induced by the Ras
      oncoprotein, which does not activate Stat3 signaling. In addition, three
      independent clones of NIH 3T3 cells stably overexpressing Stat3beta were
      generated and characterized, demonstrating that Stat3beta overexpression does not
      have a toxic effect on cell viability. These Stat3beta-overexpressing clones were
      shown to be deficient in Stat3-mediated signaling and refractory to Src-induced
      cell transformation. We conclude that Stat3 activation by the Src oncoprotein
      leads to specific gene regulation and that Stat3 is one of the critical signaling
      pathways involved in Src oncogenesis. Our findings provide evidence that
      oncogenesis-associated activation of Stat3 signaling is part of the process of
      malignant transformation.

PMID- 9566875
TI  - Stat3 activation is required for cellular transformation by v-src.
AB  - Stat3 activation has been associated with cytokine-induced proliferation, anti
      apoptosis, and transformation. Constitutively activated Stat3 has been found in
      many human tumors as well as v-abl- and v-src-transformed cell lines. Because of
      these correlations, we examined directly the relationship of activated Stat3 to
      cellular transformation and found that wild-type Stat3 enhances the transforming
      potential of v-src while three dominant negative Stat3 mutants inhibit v-src
      transformation. Stat3 wild-type or mutant proteins did not affect v-ras
      transformation. We conclude that Stat3 has a necessary role in v-src
      transformation.

PMID- 9566878
TI  - Ras signals to the cell cycle machinery via multiple pathways to induce anchorage
      independent growth.
AB  - Several specific cell cycle activities are dependent on cell-substratum adhesion
      in nontransformed cells, and the ability of the Ras oncoprotein to induce
      anchorage-independent growth is linked to its ability to abrogate this adhesion
      requirement. Ras signals via multiple downstream effector proteins, a synergistic
      combination of which may be required for the highly altered phenotype of fully
      transformed cells. We describe here studies on cell cycle regulation of anchorage
      independent growth that utilize Ras effector loop mutants in NIH 3T3 and Rat 6
      cells. Stable expression of activated H-Ras (12V) induced soft agar colony
      formation by both cell types, but each of three effector loop mutants (12V,35S,
      12V,37G, and 12V,40C) was defective in producing this response. Expression of all
      three possible pairwise combinations of these mutants synergized to induce
      anchorage-independent growth of NIH 3T3 cells, but only the 12V,35S-12V,37G and
      12V,37G-12V,40C combinations were complementary in Rat 6 cells. Each individual
      effector loop mutant partially relieved adhesion dependence of pRB
      phosphorylation, cyclin E-dependent kinase activity, and expression of cyclin A
      in NIH 3T3, but not Rat 6, cells. The pairwise combinations of effector loop
      mutants that were synergistic in producing anchorage-independent growth in Rat 6
      cells also led to synergistic abrogation of the adhesion requirement for these
      cell cycle activities. The relationship between complementation in producing
      anchorage-independent growth and enhancement of cell cycle activities was not as
      clear in NIH 3T3 cells that expressed pairs of mutants, implying the existence of
      either thresholds for these activities or additional requirements in the
      induction of anchorage-independent growth. Ectopic expression of cyclin D1, E, or
      A synergized with individual effector loop mutants to induce soft agar colony
      formation in NIH 3T3 cells, cyclin A being particularly effective. Taken
      together, these data indicate that Ras utilizes multiple pathways to signal to
      the cell cycle machinery and that these pathways synergize to supplant the
      adhesion requirements of specific cell cycle events, leading to anchorage
      independent growth.

PMID- 9566876
TI  - Association of transcription factor IIA with TATA binding protein is required for
      transcriptional activation of a subset of promoters and cell cycle progression in
      Saccharomyces cerevisiae.
AB  - The general transcription factor IIA (TFIIA) interacts with the TATA binding
      protein (TBP) and promoter DNA to mediate transcription activation in vitro. To
      determine if this interaction is generally required for activation of all class
      II genes in vivo, we have constructed substitution mutations in yeast TFIIA which
      compromise its ability to bind TBP. Substitution mutations in the small subunit
      of TFIIA (Toa2) at residue Y69 or W76 significantly impaired the ability of TFIIA
      to stimulate TBP-promoter binding in vitro. Gene replacement of wild-type TOA2
      with a W76E or Y69A/W76A mutant was lethal in Saccharomyces cerevisiae, while the
      Y69F/W76F mutant exhibited extremely slow growth at 30 degrees C. Both the Y69A
      and W76A mutants were conditionally lethal at higher temperatures. Light
      microscopy indicated that viable toa2 mutant strains accumulate as equal-size
      dumbbells and multibudded clumps. Transcription of the cell cycle-regulatory
      genes CLB1, CLB2, CLN1, and CTS1 was significantly reduced in the toa2 mutant
      strains, while the noncycling genes PMA1 and ENO2 were only modestly affected,
      suggesting that these toa2 mutant alleles disrupt cell cycle progression. The
      differential effect of these toa2 mutants on gene transcription was examined for
      a number of other genes. toa2 mutant strains supported high levels of CUP1, PHO5,
      TRP3, and GAL1 gene activation, but the constitutive expression of DED1 was
      significantly reduced. Activator-induced start site expression for HIS3, GAL80,
      URA1, and URA3 promoters was defective in toa2 mutant strains, suggesting that
      the TFIIA-TBP complex is important for promoters which require an activator
      dependent start site selection from constitutive to regulated expression. We
      present evidence to indicate that transcription defects in toa2 mutants can be
      both activator and promoter dependent. These results suggest that the association
      of TFIIA with TBP regulates activator-induced start site selection and cell cycle
      progression in S. cerevisiae.

PMID- 9566877
TI  - Multiple Grb2-mediated integrin-stimulated signaling pathways to ERK2/mitogen
      activated protein kinase: summation of both c-Src- and focal adhesion kinase
      initiated tyrosine phosphorylation events.
AB  - Fibronectin receptor integrin-mediated cell adhesion triggers intracellular
      signaling events such as the activation of the Ras/mitogen-activated protein
      (MAP) kinase cascade. In this study, we show that the nonreceptor protein
      tyrosine kinases (PTKs) c-Src and focal adhesion kinase (FAK) can be
      independently activated after fibronectin (FN) stimulation and that their
      combined activity promotes signaling to extracellular signal-regulated kinase 2
      (ERK2)/MAP kinase through multiple pathways upstream of Ras. FN stimulation of
      NIH 3T3 fibroblasts promotes c-Src and FAK association in the Triton-insoluble
      cell fraction, and the time course of FN-stimulated ERK2 activation paralleled
      that of Grb2 binding to FAK at Tyr-925 and Grb2 binding to Shc. Cytochalasin D
      treatment of fibroblasts inhibited FN-induced FAK in vitro kinase activity and
      signaling to ERK2, but it only partially inhibited c-Src activation. Treatment of
      fibroblasts with protein kinase C inhibitors or with the PTK inhibitor herbimycin
      A or PP1 resulted in reduced Src PTK activity, no Grb2 binding to FAK, and
      lowered levels of ERK2 activation. FN-stimulated FAK PTK activity was not
      significantly affected by herbimycin A treatment and, under these conditions, FAK
      autophosphorylation promoted Shc binding to FAK. In vitro, FAK directly
      phosphorylated Shc Tyr-317 to promote Grb2 binding, and in vivo Grb2 binding to
      Shc was observed in herbimycin A-treated fibroblasts after FN stimulation.
      Interestingly, c-Src in vitro phosphorylation of Shc promoted Grb2 binding to
      both wild-type and Phe-317 Shc. In vivo, Phe-317 Shc was tyrosine phosphorylated
      after FN stimulation of human 293T cells and its expression did not inhibit
      signaling to ERK2. Surprisingly, expression of Phe-925 FAK with Phe-317 Shc also
      did not block signaling to ERK2, whereas FN-stimulated signaling to ERK2 was
      inhibited by coexpression of an SH3 domain-inactivated mutant of Grb2. Our
      studies show that FN receptor integrin signaling upstream of Ras and ERK2 does
      not follow a linear pathway but that, instead, multiple Grb2-mediated
      interactions with Shc, FAK, and perhaps other yet-to-be-determined phosphorylated
      targets represent parallel signaling pathways that cooperate to promote maximal
      ERK2 activation.

PMID- 9566879
TI  - Alternative splicing variants of IkappaB beta establish differential NF-kappaB
      signal responsiveness in human cells.
AB  - To release transcription factor NF-kappaB into the nucleus, the mammalian IkappaB
      molecules IkappaB alpha and IkappaB beta are inactivated by phosphorylation and
      proteolytic degradation. Both proteins contain conserved signal-responsive
      phosphorylation sites and have conserved ankyrin repeats. To confer specific
      physiological functions to members of the NF-kappaB/Rel family, the different
      IkappaB molecules could vary in their specific NF-kappaB/Rel factor binding
      activities and could respond differently to activation signals. We have
      demonstrated that both mechanisms apply to differential regulation of NF-kappaB
      function by IkappaB beta relative to IkappaB alpha. Via alternative RNA
      processing, human IkappaB beta gives rise to different protein isoforms. IkappaB
      beta1 and IkappaB beta2, the major forms in human cells, differ in their carboxy
      terminal PEST sequences. IkappaB beta2 is the most abundant species in a number
      of human cell lines tested, whereas IkappaB beta1 is the only form detected in
      murine cells. These isoforms are indistinguishable in their binding preferences
      to cellular NF-kappaB/Rel homo- and heterodimers, which are distinct from those
      of IkappaB alpha, and both are constitutively phosphorylated. In unstimulated B
      cells, however, IkappaB beta1, but not IkappaB beta2, is found in the nucleus.
      Furthermore, the two forms differ markedly in their efficiency of proteolytic
      degradation after stimulation with several inducing agents tested. While IkappaB
      beta1 is nearly as responsive as IkappaB alpha, indicative of a shared activation
      mechanism, IkappaB beta2 is only weakly degraded and often not responsive at all.
      Alternative splicing of the IkappaB beta pre-mRNA may thus provide a means to
      selectively control the amount of IkappaB beta-bound NF-kappaB heteromers to be
      released under NF-kappaB stimulating conditions.

PMID- 9566880
TI  - The second catalytic domain of protein tyrosine phosphatase delta (PTP delta)
      binds to and inhibits the first catalytic domain of PTP sigma.
AB  - The LAR family protein tyrosine phosphatases (PTPs), including LAR, PTP delta,
      and PTP sigma, are transmembrane proteins composed of a cell adhesion molecule
      like ectodomain and two cytoplasmic catalytic domains: active D1 and inactive D2.
      We performed a yeast two-hybrid screen with the first catalytic domain of PTP
      sigma (PTP sigma-D1) as bait to identify interacting regulatory proteins. Using
      this screen, we identified the second catalytic domain of PTP delta (PTP delta
      D2) as an interactor of PTP sigma-D1. Both yeast two-hybrid binding assays and
      coprecipitation from mammalian cells revealed strong binding between PTP sigma-D1
      and PTP delta-D2, an association which required the presence of the wedge
      sequence in PTP sigma-D1, a sequence recently shown to mediate D1-D1
      homodimerization in the phosphatase RPTP alpha. This interaction was not
      reciprocal, as PTP delta-D1 did not bind PTP sigma-D2. Addition of a glutathione
      S-transferase (GST)-PTP delta-D2 fusion protein (but not GST alone) to GST-PTP
      sigma-D1 led to approximately 50% inhibition of the catalytic activity of PTP
      sigma-D1, as determined by an in vitro phosphatase assay against p
      nitrophenylphosphate. A similar inhibition of PTP sigma-D1 activity was obtained
      with coimmunoprecipitated PTP delta-D2. Interestingly, the second catalytic
      domains of LAR (LAR-D2) and PTP sigma (PTP sigma-D2), very similar in sequence to
      PTP delta-D2, bound poorly to PTP sigma-D1. PTP delta-D1 and LAR-D1 were also
      able to bind PTP delta-D2, but more weakly than PTP sigma-D1, with a binding
      hierarchy of PTP sigma-D1 >> PTP delta-D1 > LAR-D1. These results suggest that
      association between PTP sigma-D1 and PTP delta-D2, possibly via receptor
      heterodimerization, provides a negative regulatory function and that the second
      catalytic domains of this and likely other receptor PTPs, which are often
      inactive, may function instead to regulate the activity of the first catalytic
      domains.

PMID- 9566881
TI  - The HMG domain protein SSRP1/PREIIBF is involved in activation of the human
      embryonic beta-like globin gene.
AB  - The human embryonic beta-like globin (epsilon-globin) gene is expressed in
      primitive erythroid cells of the yolk sac during the first few weeks of
      development. We have previously shown that developmental stage-specific
      expression of the epsilon-globin gene is mediated by multiple positive and
      negative regulatory elements upstream of the start of transcription. Of
      particular interest is one positive regulatory element, PRE II, that works
      together with other elements (PRE I and PRE V) to confer developmental stage-
      and/or tissue-specific expression on a minimal promoter. An approximately 85- to
      90-kDa PRE II binding factor (PREIIBF) was identified in the nuclei of erythroid
      cells and shown to bind specifically to a novel 19-bp region within PRE II;
      binding of this protein to PRE II resulted in bending of the target DNA and was
      required for promoter activation. In this report, we present the cDNA expression
      cloning of PREIIBF. The cDNA encodes a previously identified member of the HMG
      domain family of DNA binding proteins termed SSRP1. By a number of biochemical
      and immunological criteria, recombinant SSRP1 appears to be identical to the
      PREII binding factor from erythroid nuclei. A hallmark of HMG domain proteins is
      their ability to bend their target DNAs; therefore, as we speculated previously,
      DNA bending by SSRP1/PREIIBF may contribute to the mechanism by which PRE II
      synergizes with other regulatory elements located upstream and downstream. In
      contrast with reports from other investigators, we demonstrate that SSRP1 binds
      DNA with clear sequence specificity. Moreover, we show that SSRP1/PREIIBF lacks a
      classical activation domain but that binding by this protein to PRE II is
      required for activation of a minimal promoter in stable erythroid cell lines.
      These studies provide the first evidence that SSRP1 plays a role in
      transcriptional regulation. SSRP1/PREIIBF may serve an architectural function by
      helping to coordinate the assembly of a multiprotein complex required for stage
      specific regulation of the human epsilon-globin gene.

PMID- 9566882
TI  - Cooperative Pho2-Pho4 interactions at the PHO5 promoter are critical for binding
      of Pho4 to UASp1 and for efficient transactivation by Pho4 at UASp2.
AB  - The activation of the PHO5 gene in Saccharomyces cerevisiae in response to
      phosphate starvation critically depends on two transcriptional activators, the
      basic helix-loop-helix protein Pho4 and the homeodomain protein Pho2. Pho4 acts
      through two essential binding sites corresponding to the regulatory elements
      UASp1 and UASp2. Mutation of either of them results in a 10-fold decrease in
      promoter activity, and mutation of both sites renders the promoter totally
      uninducible. The role of Pho4 appears relatively straightforward, but the
      mechanism of action of Pho2 had remained elusive. By in vitro footprinting, we
      have recently mapped multiple Pho2 binding sites adjacent to the Pho4 sites, and
      by mutating them individually or in combination, we now show that each of them
      contributes to PHO5 promoter activity. Their function is not only to recruit Pho2
      to the promoter but to allow cooperative binding of Pho4 together with Pho2.
      Cooperativity requires DNA binding of Pho2 to its target sites and Pho2-Pho4
      interactions. A Pho4 derivative lacking the Pho2 interaction domain is unable to
      activate the promoter, but testing of UASp1 and UASp2 individually in a minimal
      CYC1 promoter reveals a striking difference between the two UAS elements. UASp1
      is fully inactive, presumably because the Pho4 derivative is not recruited to its
      binding site. In contrast, UASp2 activates strongly in a Pho2-independent manner.
      From in vivo footprinting experiments and activity measurements with a promoter
      variant containing two UASp2 elements, we conclude that at UASp2, Pho2 is mainly
      required for the ability of Pho4 to transactivate.

PMID- 9566883
TI  - The N-terminal domain of IkappaB alpha masks the nuclear localization signal(s)
      of p50 and c-Rel homodimers.
AB  - Members of the Rel/NF-kappaB family of transcription factors are related to each
      other over a region of about 300 amino acids called the Rel Homology Domain
      (RHD), which governs DNA binding, dimerization, and binding to inhibitor. At the
      C-terminal end of the RHD, each protein has a nuclear localization signal (NLS).
      The crystal structures of the p50 and RelA family members show that the RHD
      consists of two regions: an N-terminal section which contains some of the DNA
      contacts and a C-terminal section which contains the remaining DNA contacts and
      controls dimerization. In unstimulated cells, the homo- or heterodimeric Rel/NF
      kappaB proteins are cytoplasmic by virtue of binding to an inhibitor protein
      (IkappaB) which somehow masks the NLS of each member of the dimer. The IkappaB
      proteins consist of an ankyrin-repeat-containing domain that is required for
      binding to dimers and N- and C-terminal domains that are dispensable for binding
      to most dimers. In this study, we examined the interaction between IkappaB alpha
      and Rel family homodimers by mutational analysis. We show that (i) the
      dimerization regions of p50, RelA, and c-Rel are sufficient for binding to
      IkappaB alpha, (ii) the NLSs of RelA and c-Rel are not required for binding to
      IkappaB alpha but do stabilize the interaction, (iii) the NLS of p50 is required
      for binding to IkappaB alpha, (iv) only certain residues within the p50 NLS are
      required for binding, and (v) in a p50-IkappaB alpha complex or a c-Rel-IkappaB
      alpha complex, the N terminus of IkappaB alpha either directly or indirectly
      masks one or both of the dimer NLSs.

PMID- 9566884
TI  - Two distinct domains in Staf to selectively activate small nuclear RNA-type and
      mRNA promoters.
AB  - Staf is a transcriptional activator of prime importance for enhanced
      transcription of small nuclear (snRNA) and snRNA-type genes transcribed by RNA
      polymerases II and III (Pol II and III). In addition to this activity, it also
      possesses the capacity to stimulate expression from an RNA polymerase II mRNA
      promoter. This promiscuous activator thus provides a useful model system for
      studying the mechanism by which one single transcription factor can activate a
      large variety of promoters. Here, we report the use of in vivo assays to identify
      the Staf activation domains involved in promoter selectivity. Analysis of Staf
      mutants reveals the existence of two physically and functionally distinct
      regions, outside of the DNA binding domain, responsible for mediating selective
      transcriptional activation. While a 93-amino-acid domain, with the striking
      presence of four repeated units, is specialized for transcriptional activation of
      an mRNA promoter, a segment of only 18 amino acids, with a critical Leu-213
      residue, acts specifically on Pol II and Pol III snRNA and snRNA-type promoters.
      In addition, this study disclosed the fundamental importance of invariant leucine
      and aspartic acid residues located in each repeat unit of the mRNA activation
      domain. Staf is therefore the first transcriptional activator described so far to
      harbor two physically and functionally distinct activator domains. This finding
      suggests that the same activator can contact different, specialized transcription
      complexes formed on different types of basal promoters through promoter-specific
      transactivation pathways.

PMID- 9566885
TI  - Increased c-fos mRNA expression by human fibroblasts contracting stressed
      collagen matrices.
AB  - We studied early changes in gene expression during fibroblast contraction of
      stressed collagen matrices. The level of c-fos mRNA increased dramatically and
      peaked 50 to 60 min after matrix contraction was initiated. This response did not
      require serum and could not be accounted for simply by disruption of the actin
      cytoskeleton. Increased c-fos mRNA levels required Ca2+ influx but not the cyclic
      AMP or extracellular signal-regulated kinase (ERK 1/2) signaling pathways, both
      of which are activated when fibroblasts contract stressed collagen matrices. The
      levels of two other immediate-early genes, fosb and c-jun, also increased
      transiently after fibroblast contraction, whereas the levels of fra-1, fra-2, c
      myc, and the transcription factor NF-kappaB remained the same, indicating that
      fibroblast contraction caused changes in a selective group of genes. The increase
      in c-fos mRNA during contraction of stressed collagen matrices may reflect a
      unique role for c-fos in mechanoregulated events at the end of wound repair.

PMID- 9566886
TI  - Yeast RNA polymerase II transcription in vitro is inhibited in the presence of
      nucleotide excision repair: complementation of inhibition by Holo-TFIIH and
      requirement for RAD26.
AB  - The Saccharomyces cerevisiae transcription factor IIH (TFIIH) is essential both
      for transcription by RNA polymerase II (RNAP II) and for nucleotide excision
      repair (NER) of damaged DNA. We have established cell extracts which support RNAP
      II transcription from the yeast CYC1 promoter or NER of transcriptionally silent
      damaged DNA on independent plasmid templates and substrates. When plasmid
      templates and substrates for both processes are simultaneously incubated with
      these extracts, transcription is significantly inhibited. This inhibition is
      strictly dependent on active NER and can be complemented with purified holo
      TFIIH. These results suggest that in the presence of active NER, TFIIH is
      preferentially mobilized from the basal transcription machinery for use in NER.
      Inhibition of transcription in the presence of active NER requires the RAD26
      gene, the yeast homolog of the human Cockayne syndrome group B gene (CSB).

PMID- 9566887
TI  - Assembly of T-antigen double hexamers on the simian virus 40 core origin requires
      only a subset of the available binding sites.
AB  - Initiation of simian virus 40 (SV40) DNA replication is dependent upon the
      assembly of two T-antigen (T-ag) hexamers on the SV40 core origin. To further
      define the oligomerization mechanism, the pentanucleotide requirements for T-ag
      assembly were investigated. Here, we demonstrate that individual pentanucleotides
      support hexamer formation, while particular pairs of pentanucleotides suffice for
      the assembly of T-ag double hexamers. Related studies demonstrate that T-ag
      double hexamers formed on "active pairs" of pentanucleotides catalyze a set of
      previously described structural distortions within the core origin. For the four
      pentanucleotide-containing wild-type SV40 core origin, footprinting experiments
      indicate that T-ag double hexamers prefer to bind to pentanucleotides 1 and 3.
      Collectively, these experiments demonstrate that only two of the four
      pentanucleotides in the core origin are necessary for T-ag assembly and the
      induction of structural changes in the core origin. Since all four
      pentanucleotides in the wild-type origin are necessary for extensive DNA
      unwinding, we concluded that the second pair of pentanucleotides is required at a
      step subsequent to the initial assembly process.

PMID- 9566888
TI  - Ski6p is a homolog of RNA-processing enzymes that affects translation of non
      poly(A) mRNAs and 60S ribosomal subunit biogenesis.
AB  - We mapped and cloned SKI6 of Saccharomyces cerevisiae, a gene that represses the
      copy number of the L-A double-stranded RNA virus, and found that it encodes an
      essential 246-residue protein with homology to a tRNA-processing enzyme, RNase
      PH. The ski6-2 mutant expressed electroporated non-poly(A) luciferase mRNAs 8- to
      10-fold better than did the isogenic wild type. No effect of ski6-2 on expression
      of uncapped or normal mRNAs was found. Kinetics of luciferase synthesis and
      direct measurement of radiolabeled electroporated mRNA indicate that the primary
      effect of Ski6p was on efficiency of translation rather than on mRNA stability.
      Both ski6 and ski2 mutants show hypersensitivity to hygromycin, suggesting
      functional alteration of the translation apparatus. The ski6-2 mutant has normal
      amounts of 40S and 60S ribosomal subunits but accumulates a 38S particle
      containing 5'-truncated 25S rRNA but no 5.8S rRNA, apparently an incomplete or
      degraded 60S subunit. This suggests an abnormality in 60S subunit assembly. The
      ski6-2 mutation suppresses the poor expression of the poly(A)- viral mRNA in a
      strain deficient in the 60S ribosomal protein L4. Thus, a ski6 mutation bypasses
      the requirement of the poly(A) tail for translation, allowing better translation
      of non-poly(A) mRNA, including the L-A virus mRNA which lacks poly(A). We
      speculate that the derepressed translation of non-poly(A) mRNAs is due to
      abnormal (but full-size) 60S subunits.

PMID- 9566889
TI  - Dimerization by translation initiation factor 2 kinase GCN2 is mediated by
      interactions in the C-terminal ribosome-binding region and the protein kinase
      domain.
AB  - The protein kinase GCN2 stimulates translation of the transcriptional activator
      GCN4 in yeast cells starved for amino acids by phosphorylating translation
      initiation factor 2. Several regulatory domains, including a pseudokinase domain,
      a histidyl-tRNA synthetase (HisRS)-related region, and a C-terminal (C-term)
      segment required for ribosome association, have been identified in GCN2. We used
      the yeast two-hybrid assay, coimmunoprecipitation analysis, and in vitro binding
      assays to investigate physical interactions between the different functional
      domains of GCN2. A segment containing about two thirds of the protein kinase (PK)
      catalytic domain and another containing the C-term region of GCN2 interacted with
      themselves in the two-hybrid assay, and both the PK and the C-term domains could
      be coimmunoprecipitated with wild-type GCN2 from yeast cell extracts. In
      addition, in vitro-translated PK and C-term segments showed specific binding in
      vitro to recombinant glutathione S-transferase (GST)-PK and GST-C-term fusion
      proteins, respectively. Wild-type GCN2 could be coimmunoprecipitated with a full
      length LexA-GCN2 fusion protein from cell extracts, providing direct evidence for
      dimerization by full-length GCN2 molecules. Deleting the C-term or PK segments
      abolished or reduced, respectively, the yield of GCN2-LexA-GCN2 complexes. These
      results provide in vivo and in vitro evidence that GCN2 dimerizes through self
      interactions involving the C-term and PK domains. The PK domain showed pairwise
      in vitro binding interactions with the pseudokinase, HisRS, and C-term domains;
      additionally, the HisRS domain interacted with the C-term region. We propose that
      physical interactions between the PK domain and its flanking regulatory regions
      and dimerization through the PK and C-term domains both play important roles in
      restricting GCN2 kinase activity to amino acid-starved cells.

PMID- 9566890
TI  - The Drosophila polycomb group protein Psc contacts ph and Pc through specific
      conserved domains.
AB  - The Polycomb group proteins are transcriptional repressors that are thought to
      act through multimeric nuclear complexes. We show that ph and Psc coprecipitate
      with Pc from nuclear extracts. We have analyzed the domains required for the
      association of Psc with ph and Pc by using the yeast two-hybrid system and an in
      vitro protein-binding assay. Psc and ph interact through regions of sequence
      conservation with mammalian homologs, i.e., the H1 domain of ph (amino acids 1297
      to 1418) and the helix-turn-helix-containing region of Psc (amino acids 336 to
      473). Psc contacts Pc primarily at the helix-turn-helix-containing region of Psc
      (amino acids 336 to 473), but also at the ring finger (amino acids 250 to 335).
      The Pc chromobox is not required for this interaction. We discuss the implication
      of these results for the nature of the complexes formed by Polycomb group
      proteins.

PMID- 9566891
TI  - Fission yeast rad12+ regulates cell cycle checkpoint control and is homologous to
      the Bloom's syndrome disease gene.
AB  - The human BLM gene is a member of the Escherichia coli recQ helicase family,
      which includes the Saccharomyces cerevisiae SGS1 and human WRN genes. Defects in
      BLM are responsible for the human disease Bloom's syndrome, which is
      characterized in part by genomic instability and a high incidence of cancer. Here
      we describe the cloning of rad12+, which is the fission yeast homolog of BLM and
      is identical to the recently reported rhq1+ gene. We showed that rad12 null cells
      are sensitive to DNA damage induced by UV light and gamma radiation, as well as
      to the DNA synthesis inhibitor hydroxyurea. Overexpression of the wild-type
      rad12+ gene also leads to sensitivity to these agents and to defects associated
      with the loss of the S-phase and G2-phase checkpoint control. We showed
      genetically and biochemically that rad12+ acts upstream from rad9+, one of the
      fission yeast G2 checkpoint control genes, in regulating exit from the S-phase
      checkpoint. The physical chromosome segregation defects seen in rad12 null cells
      combined with the checkpoint regulation defect seen in the rad12+ overproducer
      implicate rad12+ as a key coupler of chromosomal integrity with cell cycle
      progression.

PMID- 9566892
TI  - c-Maf interacts with c-Myb to regulate transcription of an early myeloid gene
      during differentiation.
AB  - The MafB transcriptional activator plays a pivotal role in regulating lineage
      specific gene expression during hematopoiesis by repressing Ets-1-mediated
      transcription of key erythroid-specific genes in myeloid cells. To determine the
      effects of Maf family proteins on the transactivation of myeloid-specific genes
      in myeloid cells, we tested the ability of c-Maf to influence Ets-1- and c-Myb
      dependent CD13/APN transcription. Expression of c-Maf in human immature
      myeloblastic cells inhibited CD13/APN-driven reporter gene activity (85 to 95%
      reduction) and required the binding of both c-Myb and Ets, but not Maf, to the
      promoter fragment. c-Maf's inhibition of CD13/APN expression correlates with its
      ability to physically associate with c-Myb. While c-Maf mRNA and protein levels
      remain constant during myeloid differentiation, formation of inhibitory Myb-Maf
      complexes was developmentally regulated, with their levels being highest in
      immature myeloid cell lines and markedly decreased in cell lines representing
      later developmental stages. This pattern matched that of CD13/APN reporter gene
      expression, indicating that Maf modulation of c-Myb activity may be an important
      mechanism for the control of gene transcription during hematopoietic cell
      development.

PMID- 9566893
TI  - Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint.
AB  - Saccharomyces cerevisiae BUB1 encodes a protein kinase required for spindle
      assembly checkpoint function. In the presence of spindle damage, BUB1 is required
      to prevent cell cycle progression into anaphase. We have identified a dominantly
      acting BUB1 allele that appears to activate the spindle assembly checkpoint
      pathway in cells with undamaged spindles. High-level expression of BUB1-5 did not
      cause detectable spindle damage, yet it delayed yeast cells in mitosis at a stage
      following bipolar spindle assembly but prior to anaphase spindle elongation.
      Delayed cells possessed a G2 DNA content and elevated Clb2p mitotic cyclin
      levels. Unlike cells delayed in mitosis by spindle damage or MPS1 kinase
      overexpression, hyperphosphorylated forms of the Mad1p checkpoint protein did not
      accumulate. Similar to cells overexpressing MPS1, the BUB1-5 delay was dependent
      upon the functions of the other checkpoint genes, including BUB2 and BUB3 and
      MAD1, MAD2, and MAD3. We found that the mitotic delay caused by BUB1-5 or MPS1
      overexpression was interdependent upon the function of the other. This suggests
      that the Bub1p and Mps1p kinases act together at an early step in generating the
      spindle damage signal.

PMID- 9566894
TI  - Negative regulation of DNA replication by the retinoblastoma protein is mediated
      by its association with MCM7.
AB  - A yeast two-hybrid screen was employed to identify human proteins that
      specifically bind the amino-terminal 400 amino acids of the retinoblastoma (Rb)
      protein. Two independent cDNAs resulting from this screen were found to encode
      the carboxy-terminal 137 amino acids of MCM7, a member of a family of proteins
      that comprise replication licensing factor. Full-length Rb and MCM7 form protein
      complexes in vitro, and the amino termini of two Rb-related proteins, p107 and
      p130, also bind MCM7. Protein complexes between Rb and MCM7 were also detected in
      anti-Rb immunoprecipitates prepared from human cells. The amino-termini of Rb and
      p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus
      in vitro DNA replication assay system. These data provide the first evidence that
      Rb and Rb-related proteins can directly regulate DNA replication and that
      components of licensing factor are targets of the products of tumor suppressor
      genes.

PMID- 9566895
TI  - Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively
      eliminated from the nucleus at the onset of S phase.
AB  - In a two-hybrid screen for proteins that interact with human PCNA, we identified
      and cloned a human protein (hCdc18) homologous to yeast CDC6/Cdc18 and human
      Orc1. Unlike yeast, in which the rapid and total destruction of CDC6/Cdc18
      protein in S phase is a central feature of DNA replication, the total level of
      the human protein is unchanged throughout the cell cycle. Epitope-tagged protein
      is nuclear in G1 and cytoplasmic in S-phase cells, suggesting that DNA
      replication may be regulated by either the translocation of this protein between
      the nucleus and the cytoplasm or the selective degradation of the protein in the
      nucleus. Mutation of the only nuclear localization signal of this protein does
      not alter its nuclear localization, implying that the protein is translocated to
      the nucleus through its association with other nuclear proteins. Rapid
      elimination of the nuclear pool of this protein after the onset of DNA
      replication and its association with human Orc1 protein and cyclin-cdks supports
      its identification as human CDC6/Cdc18 protein.

PMID- 9566896
TI  - Tumor suppressor p53 can participate in transcriptional induction of the GADD45
      promoter in the absence of direct DNA binding.
AB  - The GADD45 gene is a growth arrest-associated gene that is induced by certain DNA
      damaging agents and other stresses, such as starvation, in all mammalian cells.
      In addition to a strong p53-binding element in an intronic sequence, we have
      recently found that p53, while not required or sufficient alone, may contribute
      to the stress responsiveness of the promoter. Much of the responsiveness was
      localized to a GC-rich motif in the proximal promoter which contains multiple
      Egr1 sites and a larger WT1 site; this 20-bp WT1 motif is identical to the WT1
      binding site in the PDGF-A gene. In extracts from a human breast carcinoma cell
      line expressing p53 and WT1, which is known to associate with p53 in vivo,
      evidence was obtained that these proteins are in a complex that binds this 20-bp
      element. A combination of p53 and WT1 expression vectors strongly induced a
      GADD45-reporter construct, while mutation of the WT1-Egr1 site in the promoter
      prevented this induction. Abrogation of p53 function by a dominant-negative
      vector or abrogation of WT1 function by an antisense vector markedly reduced the
      induction of this promoter. Since p53 does not bind directly to the promoter,
      these results indicate that p53 can contribute to the positive regulation of a
      promoter by protein-protein interactions.

PMID- 9566897
TI  - Destabilization of yeast micro- and minisatellite DNA sequences by mutations
      affecting a nuclease involved in Okazaki fragment processing (rad27) and DNA
      polymerase delta (pol3-t).
AB  - We examined the effects of mutations in the Saccharomyces cerevisiae RAD27
      (encoding a nuclease involved in the processing of Okazaki fragments) and POL3
      (encoding DNA polymerase delta) genes on the stability of a minisatellite
      sequence (20-bp repeats) and microsatellites (1- to 8-bp repeat units). Both the
      rad27 and pol3-t mutations destabilized both classes of repeats, although the
      types of tract alterations observed in the two mutant strains were different. The
      tract alterations observed in rad27 strains were primarily additions, and those
      observed in pol3-t strains were primarily deletions. Measurements of the rates of
      repetitive tract alterations in strains with both rad27 and pol3-t indicated that
      the stimulation of microsatellite instability by rad27 was reduced by the effects
      of the pol3-t mutation. We also found that rad27 and pol3-01 (an allele carrying
      a mutation in the "proofreading" exonuclease domain of DNA polymerase delta)
      mutations were synthetically lethal.

PMID- 9566898
TI  - Mutants of the yeast Yarrowia lipolytica defective in protein exit from the
      endoplasmic reticulum are also defective in peroxisome biogenesis.
AB  - Mutations in the SEC238 and SRP54 genes of the yeast Yarrowia lipolytica not only
      cause temperature-sensitive defects in the exit of the precursor form of alkaline
      extracellular protease and of other secretory proteins from the endoplasmic
      reticulum and in protein secretion but also lead to temperature-sensitive growth
      in oleic acid-containing medium, the metabolism of which requires the assembly of
      functionally intact peroxisomes. The sec238A and srp54KO mutations at the
      restrictive temperature significantly reduce the size and number of peroxisomes,
      affect the import of peroxisomal matrix and membrane proteins into the organelle,
      and significantly delay, but do not prevent, the exit of two peroxisomal membrane
      proteins, Pex2p and Pex16p, from the endoplasmic reticulum en route to the
      peroxisomal membrane. Mutations in the PEX1 and PEX6 genes, which encode members
      of the AAA family of N-ethylmaleimide-sensitive fusion protein-like ATPases, not
      only affect the exit of precursor forms of secretory proteins from the
      endoplasmic reticulum but also prevent the exit of the peroxisomal membrane
      proteins Pex2p and Pex16p from the endoplasmic reticulum and cause the
      accumulation of an extensive network of endoplasmic reticulum membranes. None of
      the peroxisomal matrix proteins tested associated with the endoplasmic reticulum
      in sec238A, srp54KO, pex1-1, and pex6KO mutant cells. Our data provide evidence
      that the endoplasmic reticulum is required for peroxisome biogenesis and suggest
      that in Y. lipolytica, the trafficking of some membrane proteins, but not matrix
      proteins, to the peroxisome occurs via the endoplasmic reticulum, results in
      their glycosylation within the lumen of the endoplasmic reticulum, does not
      involve transport through the Golgi, and requires the products encoded by the
      SEC238, SRP54, PEX1, and PEX6 genes.

PMID- 9566899
TI  - Two distinct types of repression domain in engrailed: one interacts with the
      groucho corepressor and is preferentially active on integrated target genes.
AB  - Active transcriptional repression has been characterized as a function of many
      regulatory factors. It facilitates combinatorial regulation of gene expression by
      allowing repressors to be dominant over activators under certain conditions.
      Here, we show that the Engrailed protein uses two distinct mechanisms to repress
      transcription. One activity is predominant under normal transient transfection
      assay conditions in cultured cells. A second activity is predominant in an in
      vivo active repression assay. The domain mediating the in vivo activity (eh1) is
      highly conserved throughout several classes of homeoproteins and interacts
      specifically with the Groucho corepressor. While eh1 shows only weak activity in
      transient transfections, much stronger activity is seen in culture when an
      integrated target gene is used. In this assay, the relative activities of
      different repression domains closely parallel those seen in vivo, with eh1
      showing the predominant activity. Reducing the amounts of repressor and target
      gene in a transient transfection assay also increases the sensitivity of the
      assay to the Groucho interaction domain, albeit to a lesser extent. This suggests
      that it utilizes rate-limiting components that are relatively low in abundance.
      Since Groucho itself is abundant in these cells, the results suggest that a
      limiting component is recruited effectively by the repressor-corepressor complex
      only on integrated target genes.

PMID- 9566900
TI  - Tumor necrosis factor alpha gene regulation: enhancement of C/EBPbeta-induced
      activation by c-Jun.
AB  - Tumor necrosis factor alpha (TNF alpha) is a key regulatory cytokine whose
      expression is controlled by a complex set of stimuli in a variety of cell types.
      Previously, we found that the monocyte/macrophage-enriched nuclear transcription
      factor C/EBPbeta played an important role in the regulation of the TNF alpha gene
      in myelomonocytic cells. Abundant evidence suggests that other transcription
      factors participate as well. Here we have analyzed interactions between C/EBPbeta
      and c-Jun, a component of the ubiquitously expressed AP-1 complex. In phorbol
      myristate acetate (PMA)-treated Jurkat T cells, which did not possess endogenous
      C/EBPbeta, expression of c-Jun by itself had relatively little effect on TNF
      alpha promoter activity. However, the combination of C/EBPbeta and c-Jun was
      synergistic, resulting in greater than 130-fold activation. This effect required
      both the leucine zipper and DNA binding domains, but not the transactivation
      domain, of c-Jun, plus the AP-1 binding site centered 102/103 bp upstream of the
      transcription start site in the TNF alpha promoter. To determine if C/EBPbeta and
      c-Jun might cooperate to regulate the cellular TNF alpha gene in myelomonocytic
      cells, U937 cells that possess endogenous C/EBPbeta and were stably transfected
      with either wild-type c-Jun or the transactivation domain deletion mutant (TAM
      67) were examined. U937 cells expressing ectopic wild-type c-Jun or TAM-67
      secreted over threefold more TNF alpha than the control line in response to PMA
      plus lipopolysaccharide. Transient transfection of the U937 cells expressing TAM
      67 suggested that TAM-67 binding to the -106/-99-bp AP-1 binding site cooperated
      with endogenous C/EBPbeta in the activation of the -120 TNF alpha promoter
      reporter. DNA binding assays using oligonucleotides derived from the TNF alpha
      promoter suggested that C/EBPbeta and c-Jun interact in vitro and that the
      interaction may be DNA dependent. Our data demonstrate that the TNF alpha gene is
      regulated by the interaction of the ubiquitous AP-1 complex protein c-Jun and the
      monocyte/macrophage-enriched transcription factor C/EBPbeta and that this
      interaction contributes to the expression of the cellular TNF alpha gene in
      myelomonocytic cells. This interaction was unique in that it did not require the
      c-Jun transactivation domain, providing new insight into the cell-type-specific
      regulation of the TNF alpha gene.

PMID- 9566902
TI  - Interaction of tumor necrosis factor receptor-associated factor signaling
      proteins with the latent membrane protein 1 PXQXT motif is essential for
      induction of epidermal growth factor receptor expression.
AB  - The Epstein-Barr virus latent membrane protein 1 (LMP1) oncoprotein causes
      multiple cellular changes, including induction of epidermal growth factor
      receptor (EGFR) expression and activation of the NF-kappaB transcription factor.
      LMP1 and the cellular protein CD40, which also induces EGFR expression, interact
      with the tumor necrosis factor receptor-associated factor (TRAF) proteins. The
      LMP1 carboxy-terminal activation region 1 signaling domain interacts specifically
      with the TRAFs and is essential for EGFR induction through a mechanism
      independent of NF-kappaB alone. LMP1 and CD40 share a common TRAF binding motif,
      PXQXT. In this study, the PXQXT motifs in both LMP1 and CD40 were altered and
      mutant proteins were analyzed for induction of EGFR expression. Replacement of
      the T residue with A in CD40 completely blocked induction of the EGFR, while the
      same mutation in LMP1 did not affect EGFR induction. Replacement of both P and Q
      residues with A's in LMP1 reduced EGFR induction by >75%, while deletion of PXQXT
      blocked EGFR induction. These results genetically link EGFR induction by LMP1 to
      the TRAF signaling pathway. Overexpression of TRAF2 potently activates NF-kappaB,
      although TRAF2 did not induce expression of the EGFR either alone or in
      combination with TRAF1 and TRAF3. In vivo analyses of the interaction of the
      TRAFs with LMP1 variants mutated in the PXQXT domain indicate that high-level
      induction of EGFR expression requires interaction with TRAF1, -2, and -3.
      However, exogenous expression of TRAF3 decreased EGFR induction mediated by
      either LMP1 or CD40. These data suggest that TRAF-mediated activation of EGFR
      expression requires assembly of a complex containing the appropriate
      stoichiometry of TRAF proteins clustered at the cell membrane with LMP1.

PMID- 9566901
TI  - The Drosophila esc and E(z) proteins are direct partners in polycomb group
      mediated repression.
AB  - The extra sex combs (esc) and Enhancer of zeste [E(z)] proteins are members of
      the Drosophila Polycomb group (Pc-G) of transcriptional repressors. Here we
      present evidence for direct physical interaction between the esc and E(z)
      proteins using yeast two-hybrid and in vitro binding assays. In addition,
      coimmunoprecipitation from embryo extracts demonstrates association of esc and
      E(z) in vivo. We have delimited the esc-binding domain of E(z) to an N-terminal
      33-amino-acid region. Furthermore, we demonstrate that site-directed mutations in
      the esc protein previously shown to impair esc function in vivo disrupt esc-E(z)
      interactions in vitro. We also show an in vitro interaction between the heed and
      EZH1 proteins, which are human homologs of esc and E(z), respectively. These
      results suggest that the esc-E(z) molecular partnership has been conserved in
      evolution. Previous studies suggested that esc is primarily involved in the early
      stages of Pc-G-mediated silencing during embryogenesis. However, E(z) is
      continuously required in order to maintain chromosome binding by other Pc-G
      proteins. In light of these earlier observations and the molecular data presented
      here, we discuss how esc-E(z) protein complexes may contribute to transcriptional
      silencing by the Pc-G.

PMID- 9566903
TI  - Regulation of proliferation-survival decisions during tumor cell hypoxia.
AB  - Hypoxia may influence tumor biology in paradoxically opposing ways: it is lethal
      as a direct stress trigger, yet hypoxic zones in solid tumors harbor viable cells
      which are particularly resistant to treatment and contribute importantly to
      disease relapse. To examine mechanisms underlying growth-survival decisions
      during hypoxia, we have compared genetically related transformed and
      untransformed fibroblast cells in vitro for proliferation, survival,
      clonogenicity, cell cycle, and p53 expression. Hypoxia induces G0/G1 arrest in
      primary fibroblasts but triggers apoptosis in oncogene-transformed derivatives.
      Unexpectedly, the mechanism of apoptosis is seen to require accumulated acidosis
      and is rescued by enhanced buffering. The direct effect of hypoxia under
      nonacidotic conditions is unique to transformed cells in that they override the
      hypoxic G0/G1 arrest of primary cells. Moreover, when uncoupled from acidosis,
      hypoxia enhances tumor cell viability and clonogenicity relative to normoxia. p53
      is correspondingly upregulated in response to hypoxia-induced acidosis but
      downregulated during hypoxia without acidosis. Hypoxia may thus produce both
      treatment resistance and a growth advantage. Given strong evidence that hypoxic
      regions in solid tumors are often nonacidotic (G. Helmlinger, F. Yuan, M.
      Dellian, and R. K. Jain, Nat. Med. 3:177-182, 1997), this behavior may influence
      relapse and implicates such cells as potentially important therapeutic targets.

PMID- 9566905
TI  - Axil, a member of the Axin family, interacts with both glycogen synthase kinase
      3beta and beta-catenin and inhibits axis formation of Xenopus embryos.
AB  - Using a yeast two-hybrid method, we identified a novel protein which interacts
      with glycogen synthase kinase 3beta (GSK-3beta). This protein had 44% amino acid
      identity with Axin, a negative regulator of the Wnt signaling pathway. We
      designated this protein Axil for Axin like. Like Axin, Axil ventralized Xenopus
      embryos and inhibited Xwnt8-induced Xenopus axis duplication. Axil was
      phosphorylated by GSK-3beta. Axil bound not only to GSK-3beta but also to beta
      catenin, and the GSK-3beta-binding site of Axil was distinct from the beta
      catenin-binding site. Furthermore, Axil enhanced GSK-3beta-dependent
      phosphorylation of beta-catenin. These results indicate that Axil negatively
      regulates the Wnt signaling pathway by mediating GSK-3beta-dependent
      phosphorylation of beta-catenin, thereby inhibiting axis formation.

PMID- 9566904
TI  - Genetic evidence of a role for Lck in T-cell receptor function independent or
      downstream of ZAP-70/Syk protein tyrosine kinases.
AB  - T-cell antigen receptor (TCR) engagement results in sequential activation of the
      Src protein tyrosine kinases (PTKs) Lck and Fyn and the Syk PTKs, ZAP-70 and Syk.
      While the Src PTKs mediate the phosphorylation of TCR-associated signaling
      subunits and the phosphorylation and activation of the Syk PTKs, the lack of a
      constitutively active Syk PTK has prohibited the analysis of Lck function
      downstream of these initiating signaling events. We describe here the generation
      of an activated Syk family PTK by substituting the kinase domain of Syk for the
      homologous region in ZAP-70 (designated as KS for kinase swap). Expression of the
      KS chimera resulted in its autophosphorylation, the phosphorylation of cellular
      proteins, the upregulation of T-cell activation markers, and the induction of
      interleukin-2 gene synthesis in a TCR-independent fashion. The KS chimera and
      downstream ZAP-70 or Syk substrates, such as SLP-76, were still phosphorylated
      when expressed in Lck-deficient JCaM1.6 T cells. However, expression of the KS
      chimera in JCaM1.6 cells failed to rescue downstream signaling events,
      demonstrating a functional role for Lck beyond the activation of the ZAP-70 and
      Syk PTKs. These results indicate that downstream TCR signaling pathways may be
      differentially regulated by ZAP-70 and Lck PTKs and provide a mechanism by which
      effector functions may be selectively activated in response to TCR stimulation.

PMID- 9566906
TI  - Stepwise recruitment of components of the preinitiation complex by upstream
      activators in vivo.
AB  - Recently, it was found that if either the TATA binding protein or RNA polymerase
      II holoenzyme is artificially tethered to a promoter, transcription is activated.
      This finding provided presumptive evidence that upstream activating proteins
      function by recruiting components of the preinitiation complex (PIC) to the
      promoter. To date, however, there have been no studies demonstrating that
      upstream factors actually recruit components of the PIC to the promoter in vivo.
      Therefore, we have studied the mechanism of action of two disparate
      transactivating domains. We present a series of in vivo functional assays that
      demonstrate that each of these proteins targets different components of the PIC
      for recruitment. We show that, by targeting different components of the PIC for
      recruitment, these activating domains can cooperate with each other to activate
      transcription synergistically and that, even within one protein, two different
      activating subdomains can activate transcription synergistically by cooperating
      to recruit different components of the PIC. Finally, considering our work
      together with previous studies, we propose that certain transcription factors
      both recruit components of the PIC and facilitate steps in transcriptional
      activation that occur subsequent to recruitment.

PMID- 9566907
TI  - Ash1, a daughter cell-specific protein, is required for pseudohyphal growth of
      Saccharomyces cerevisiae.
AB  - Ash1 (for asymmetric synthesis of HO) was first uncovered in genetic screens that
      revealed its role in mating-type switching. Ash1 prevents HO expression in
      daughter cells. Because Ash1 has a zinc finger-like domain related to that of the
      GATA family of transcription factors, it presumably acts by repressing HO
      transcription. Nonswitching diploid cells also express Ash1, suggesting it could
      have functions in addition to regulation of HO expression. We show here that Ash1
      has an essential function for pseudohyphal growth. Our epistasis analyses are
      consistent with the deduction that Ash1 acts separately from the mitogen
      activated protein kinase cascade and Ste12. Similarly to the case in yeast form
      cells, Ash1 is asymmetrically localized to the nuclei of daughter cells during
      pseudohyphal growth. This asymmetric localization reveals that there is a
      previously unsuspected daughter cell-specific function necessary for pseudohyphal
      growth.

PMID- 9566908
TI  - Developmental regulation of bicoid mRNA stability is mediated by the first 43
      nucleotides of the 3' untranslated region.
AB  - During the transition from the maternal to the zygotic developmental program, the
      expression of genes important for pattern formation or cell cycle regulation
      changes dramatically. Rapid changes in gene expression are achieved in part
      through the control of mRNA stability. This report focuses on bicoid, a gene
      essential for formation of anterior embryonic structures in Drosophila
      melanogaster. bicoid mRNA is synthesized exclusively during oogenesis. Here, we
      show that bicoid mRNA stability is regulated. While bicoid mRNA is stable in
      retained oocytes, in unfertilized eggs, and during the first 2 h of
      embryogenesis, specific degradation is activated at cellularization of the
      blastoderm. To identify cis-acting sequences required for bicoid mRNA's regulated
      stability, fusions between bicoid and genes producing stable mRNAs were
      introduced into the Drosophila germ line by P-element-mediated transformation.
      The analysis of the fusion mRNAs identified a bicoid instability element (BIE)
      contained within a 43-nucleotide sequence immediately following the stop codon.
      The BIE is sufficient to destabilize the otherwise-stable ribosomal protein A1
      mRNA and is separable from the previously identified bicoid mRNA localization
      signals and from the "nanos response element." Similar mechanisms may regulate a
      class of developmentally important maternal genes whose mRNA has a temporal
      profile similar to that of bicoid.

PMID- 9566909
TI  - Distinct functions are implicated for the GATA-4, -5, and -6 transcription
      factors in the regulation of intestine epithelial cell differentiation.
AB  - Based on conserved expression patterns, three members of the GATA family of
      transcriptional regulatory proteins, GATA-4, -5, and -6, are thought to be
      involved in the regulation of cardiogenesis and gut development. Functions for
      these factors are known in the heart, but relatively little is understood
      regarding their possible roles in the regulation of gut-specific gene expression.
      In this study, we analyze the expression and function of GATA-4, -5, and -6 using
      three separate but complementary vertebrate systems, and the results support a
      function for these proteins in regulating the terminal-differentiation program of
      intestinal epithelial cells. We show that xGATA-4, -5, and -6 can stimulate
      directly activity of the promoter for the intestinal fatty acid-binding protein
      (xIFABP) gene, which is a marker for differentiated enterocytes. This is the
      first direct demonstration of a target for GATA factors in the vertebrate
      intestinal epithelium. Transactivation by xGATA-4, -5, and -6 is mediated at
      least in part by a defined proximal IFABP promoter element. The expression
      patterns for cGATA-4, -5, and -6 are markedly distinct along the proximal-distal
      villus axis. Transcript levels for cGATA-4 increase along the axis toward the
      villus tip; likewise, cGATA-5 transcripts are largely restricted to the distal
      tip containing differentiated cells. In contrast, the pattern of cGATA-6
      transcripts is complementary to cGATA-5, with highest levels detected in the
      region of proliferating progenitor cells. Undifferentiated and proliferating
      human HT-29 cells express hGATA-6 but not hGATA-4 or hGATA-5. Upon stimulation to
      differentiate, the transcript levels for hGATA-5 increase, and this occurs prior
      to increased transcription of the terminal differentiation marker intestinal
      alkaline phosphatase. At the same time, hGATA-6 steady-state transcript levels
      decline appreciably. All of the data are consistent with evolutionarily conserved
      but distinct roles for these factors in regulating the differentiation program of
      intestinal epithelium. Based on this data, we suggest that GATA-6 might function
      primarily within the proliferating progenitor population, while GATA-4 and GATA-5
      function during differentiation to activate terminal-differentiation genes
      including IFABP.

PMID- 9566910
TI  - Commitment and effector phases of the physiological cell death pathway elucidated
      with respect to Bcl-2 caspase, and cyclin-dependent kinase activities.
AB  - Physiological cell deaths occur ubiquitously throughout biology and have common
      attributes, including apoptotic morphology with mitosis-like chromatin
      condensation and prelytic genome digestion. The fundamental question is whether a
      common mechanism of dying underlies these common hallmarks of death. Here we
      describe evidence of such a conserved mechanism in different cells induced by
      distinct stimuli to undergo physiological cell death. Our genetic and
      quantitative biochemical analyses of T- and B-cell deaths reveal a conserved
      pattern of requisite components. We have dissected the role of cysteine proteases
      (caspases) in cell death to reflect two obligate classes of cytoplasmic
      activities functioning in an amplifying cascade, with upstream interleukin-1beta
      converting enzyme-like proteases activating downstream caspase 3-like caspases.
      Bcl-2 spares cells from death by punctuating this cascade, preventing the
      activation of downstream caspases while leaving upstream activity undisturbed.
      This observation permits an operational definition of the stages of the cell
      death process. Upstream steps, which are necessary but not themselves lethal, are
      modulators of the death process. Downstream steps are effectors of, and not
      dissociable from, actual death; the irreversible commitment to cell death
      reflects the initiation of this downstream phase. In addition to caspase 3-like
      proteases, the effector phase of death involves the activation in the nucleus of
      cell cycle kinases of the cyclin-dependent kinase (Cdk) family. Nuclear
      recruitment and activation of Cdk components is dependent on the caspase cascade,
      suggesting that catastrophic Cdk activity may be the actual effector of cell
      death. The conservation of the cell death mechanism is not reflected in the
      molecular identity of its individual components, however. For example, we have
      detected different cyclin-Cdk pairs in different instances of cell death. The
      ordered course of events that we have observed in distinct cases reflects
      essential thematic elements of a conserved sequence of modulatory and effector
      activities comprising a common pathway of physiological cell death.

PMID- 9566911
TI  - Molecular evolution allows bypass of the requirement for activation loop
      phosphorylation of the Cdc28 cyclin-dependent kinase.
AB  - Many protein kinases are regulated by phosphorylation in the activation loop,
      which is required for enzymatic activity. Glutamic acid can substitute for
      phosphothreonine in some proteins activated by phosphorylation, but this
      substitution (T169E) at the site of activation loop phosphorylation in the
      Saccharomyces cerevisiae cyclin-dependent kinase (Cdk) Cdc28p blocks biological
      function and protein kinase activity. Using cycles of error-prone DNA
      amplification followed by selection for successively higher levels of function,
      we identified mutant versions of Cdc28p-T169E with high biological activity. The
      enzymatic and biological activity of the mutant Cdc28p was essentially normally
      regulated by cyclin, and the mutants supported normal cell cycle progression and
      regulation. Therefore, it is not a requirement for control of the yeast cell
      cycle that Cdc28p be cyclically phosphorylated and dephosphorylated. These CDC28
      mutants allow viability in the absence of Cak1p, the essential kinase that
      phosphorylates Cdc28p-T169, demonstrating that T169 phosphorylation is the only
      essential function of Cak1p. Some growth defects remain in suppressed cak1 cdc28
      strains carrying the mutant CDC28 genes, consistent with additional nonessential
      roles for CAK1.

PMID- 9566912
TI  - Selenium deficiency reduces the abundance of mRNA for Se-dependent glutathione
      peroxidase 1 by a UGA-dependent mechanism likely to be nonsense codon-mediated
      decay of cytoplasmic mRNA.
AB  - The mammalian mRNA for selenium-dependent glutathione peroxidase 1 (Se-GPx1)
      contains a UGA codon that is recognized as a codon for the nonstandard amino acid
      selenocysteine (Sec). Inadequate concentrations of selenium (Se) result in a
      decrease in Se-GPx1 mRNA abundance by an uncharacterized mechanism that may be
      dependent on translation, independent of translation, or both. In this study, we
      have begun to elucidate this mechanism. We demonstrate using hepatocytes from
      rats fed either a Se-supplemented or Se-deficient diet for 9 to 13 weeks that Se
      deprivation results in an approximately 50-fold reduction in Se-GPx1 activity and
      an approximately 20-fold reduction in Se-GPx1 mRNA abundance. Reverse
      transcription-PCR analyses of nuclear and cytoplasmic fractions revealed that Se
      deprivation has no effect on the levels of either nuclear pre-mRNA or nuclear
      mRNA but reduces the level of cytoplasmic mRNA. The regulation of Se-GPx1 gene
      expression by Se was recapitulated in transient transfections of NIH 3T3 cells,
      and experiments were extended to examine the consequences of converting the Sec
      codon (TGA) to either a termination codon (TAA) or a cysteine codon (TGC).
      Regardless of the type of codon, an alteration in the Se concentration was of no
      consequence to the ratio of nuclear Se-GPx1 mRNA to nuclear Se-GPx1 pre-mRNA. The
      ratio of cytoplasmic Se-GPx1 mRNA to nuclear Se-GPx1 mRNA from the wild-type (TGA
      containing) allele was reduced twofold when cells were deprived of Se for 48 h
      after transfection, which has been shown to be the extent of the reduction for
      the endogenous Se-GPx1 mRNA of cultured cells incubated as long as 20 days in Se
      deficient medium. In contrast to the TGA allele, Se had no effect on expression
      of either the TAA allele or the TGC allele. Under Se-deficient conditions, the
      TAA and TGC alleles generated, respectively, 1.7-fold-less and 3-fold-more
      cytoplasmic Se-GPx1 mRNA relative to the amount of nuclear Se-GPx1 mRNA than the
      TGA allele. These results indicate that (i) under conditions of Se deprivation,
      the Sec codon reduces the abundance of cytoplasmic Se-GPx1 mRNA by a translation
      dependent mechanism and (ii) there is no additional mechanism by which Se
      regulates Se-GPx1 mRNA production. These data suggest that the inefficient
      incorporation of Sec at the UGA codon during mRNA translation augments the
      nonsense-codon-mediated decay of cytoplasmic Se-GPx1 mRNA.

PMID- 9566913
TI  - Carbon source-dependent phosphorylation of hexokinase PII and its role in the
      glucose-signaling response in yeast.
AB  - The HXK2 gene is required for a variety of regulatory effects leading to an
      adaptation for fermentative metabolism in Saccharomyces cerevisiae. However, the
      molecular basis of the specific role of Hxk2p in these effects is still unclear.
      One important feature in order to understand the physiological function of
      hexokinase PH is that it is a phosphoprotein, since protein phosphorylation is
      essential in most metabolic signal transductions in eukaryotic cells. Here we
      show that Hxk2p exists in vivo in a dimeric-monomeric equilibrium which is
      affected by phosphorylation. Only the monomeric form appears phosphorylated,
      whereas the dimer does not. The reversible phosphorylation of Hxk2p is carbon
      source dependent, being more extensive on poor carbon sources such as galactose,
      raffinose, and ethanol. In vivo dephosphorylation of Hxk2p is promoted after
      addition of glucose. This effect is absent in glucose repression mutants
      cat80/grr1, hex2/reg1, and cid1/glc7. Treatment of a glucose crude extract from
      cid1-226 (glc7-T152K) mutant cells with lambda-phosphatase drastically reduces
      the presence of phosphoprotein, suggesting that CID1/GLC7 phosphatase together
      with its regulatory HEX2/REG1 subunit are involved in the dephosphorylation of
      the Hxk2p monomer. An HXK2 mutation encoding a serine-to-alanine change at
      position 15 [HXK2 (S15A)] was to clarify the in vivo function of the
      phosphorylation of hexokinase PII. In this mutant, where the Hxk2 protein is
      unable to undergo phosphorylation, the cells could not provide glucose repression
      of invertase. Glucose induction of HXT gene expression is also affected in cells
      expressing the mutated enzyme. Although we cannot rule out a defect in the
      metabolic state of the cell as the origin of these phenomena, our results suggest
      that the phosphorylation of hexokinase is essential in vivo for glucose signal
      transduction.

PMID- 9566914
TI  - Nuclear receptor DAX-1 recruits nuclear receptor corepressor N-CoR to
      steroidogenic factor 1.
AB  - The orphan nuclear receptor steroidogenic factor 1 (SF-1) is a critical
      developmental regulator in the urogenital ridge, because mice targeted for
      disruption of the SF-1 gene lack adrenal glands and gonads. SF-1 was recently
      shown to interact with DAX-1, another orphan receptor whose tissue distribution
      overlaps that of SF-1. Naturally occurring loss-of-function mutations of the DAX
      1 gene cause the human disorder X-linked adrenal hypoplasia congenita (AHC),
      which resembles the phenotype of SF-1-deficient mice. Paradoxically, however, DAX
      1 represses the transcriptional activity of SF-1, and AHC mutants of DAX-1 lose
      repression function. To further investigate these findings, we characterized the
      interaction between SF-1 and DAX-1 and found that their interaction indeed occurs
      through a repressive domain within the carboxy terminus of SF-1. Furthermore, we
      demonstrate that DAX-1 recruits the nuclear receptor corepressor N-CoR to SF-1,
      whereas naturally occurring AHC mutations of DAX-1 permit the SF-1-DAX-1
      interaction, but markedly diminish corepressor recruitment. Finally, the
      interaction between DAX-1 and N-CoR shares similarities with that of the nuclear
      receptor RevErb and N-CoR, because the related corepressor SMRT was not
      efficiently recruited by DAX-1. Therefore, DAX-1 can serve as an adapter molecule
      that recruits nuclear receptor corepressors to DNA-bound nuclear receptors like
      SF-1, thereby extending the range of corepressor action.

PMID- 9566915
TI  - p300 mediates transcriptional stimulation by the basic helix-loop-helix
      activators of the insulin gene.
AB  - Pancreatic beta-cell-type-specific and glucose-inducible transcription of the
      insulin gene is mediated by the basic helix-loop-helix factors that bind to and
      activate expression from an E-box element within its enhancer. The E-box
      activator is a heteromeric complex composed of a beta-cell-enriched factor,
      BETA2/NeuroD, and ubiquitously distributed proteins encoded by the E2A and HEB
      genes. Previously, we demonstrated that the adenovirus type 5 E1A proteins
      repressed stimulation by the E-box activator in beta cells. In this study, our
      objective was to determine how E1A repressed activator function. The results
      indicate that E1A reduces activation by binding to and sequestering the p300
      cellular coactivator protein. Thus, we show that expression of p300 in beta cells
      can relieve inhibition by E1A, as well as potentiate activation by the endogenous
      insulin E-box transcription factors. p300 stimulated activation from GAL4 (amino
      acids 1 to 147) fusion constructs of either BETA2/NeuroD or the E2A-encoded E47
      protein. The sequences spanning the activation domains of BETA2/NeuroD (amino
      acids 156 to 355) and E47 (amino acids 1 to 99 and 325 to 432) were required for
      this response. The same region of BETA2/NeuroD was shown to be important for
      binding to p300 in vitro. The sequences of p300 involved in E47 and BETA2/NeuroD
      association resided between amino acids 1 and 1257 and 1945 and 2377,
      respectively. A mutation in p300 that abolished binding to BETA2/NeuroD also
      destroyed the ability of p300 to activate insulin E-box-directed transcription in
      beta cells. Our results indicate that physical and functional interactions
      between p300 and the E-box activator factors play an important role in insulin
      gene transcription.

PMID- 9566916
TI  - Protein tyrosine phosphatase 1B antagonizes signalling by oncoprotein tyrosine
      kinase p210 bcr-abl in vivo.
AB  - The p210 bcr-abl protein tyrosine kinase (PTK) appears to be directly responsible
      for the initial manifestations of chronic myelogenous leukemia (CML). In contrast
      to the extensive characterization of the PTK and its effects on cell function,
      relatively little is known about the nature of the protein tyrosine phosphatases
      (PTPs) that may modulate p210 bcr-abl-induced signalling. In this study, we have
      demonstrated that expression of PTP1B is enhanced specifically in various cells
      expressing p210 bcr-abl, including a cell line derived from a patient with CML.
      This effect on expression of PTP1B required the kinase activity of p210 bcr-abl
      and occurred rapidly, concomitant with maximal activation of a temperature
      sensitive mutant of the PTK. The effect is apparently specific for PTP1B since,
      among several PTPs tested, we detected no change in the levels of TCPTP, the
      closest relative of PTP1B. We have developed a strategy for identification of
      physiological substrates of individual PTPs which utilizes substrate-trapping
      mutant forms of the enzymes that retain the ability to bind to substrate but fail
      to catalyze efficient dephosphorylation. We have observed association between a
      substrate-trapping mutant of PTP1B (PTP1B-D181A) and p210 bcr-abl, but not v-Abl,
      in a cellular context. Consistent with the trapping data, we observed
      dephosphorylation of p210 bcr-abl, but not v-Abl, by PTP1B in vivo. We have
      demonstrated that PTP1B inhibited binding of the adapter protein Grb2 to p210 bcr
      abl and suppressed p210 bcr-abl-induced transcriptional activation that is
      dependent on Ras. These results illustrate selectivity in the effects of PTPs in
      a cellular context and suggest that PTP1B may function as a specific, negative
      regulator of p210 bcr-abl signalling in vivo.

PMID- 9566917
TI  - Transcription-dependent DNA transactions in the mitochondrial genome of a yeast
      hypersuppressive petite mutant.
AB  - Mitochondrial DNA (mtDNA) of Saccharomyces cerevisiae contains highly conserved
      sequences, called rep/ori, that are associated with several aspects of its
      metabolism. These rep/ori sequences confer the transmission advantage exhibited
      by a class of deletion mutants called hypersuppressive petite mutants. In
      addition, because they share features with the mitochondrial leading-strand DNA
      replication origin of mammals, rep/ori sequences have also been proposed to
      participate in mtDNA replication initiation. Like the mammalian origins, where
      transcription is used as a priming mechanism for DNA synthesis, yeast rep/ori
      sequences contain an active promoter. Although transcription is required for
      maintenance of wild-type mtDNA in yeast, the role of the rep/ori promoter as a
      cis-acting element involved in the replication of wild-type mtDNA is unclear,
      since mitochondrial deletion mutants need neither transcription nor a rep/ori
      sequence to maintain their genome. Similarly, transcription from the rep/ori
      promoter does not seem to be necessary for biased inheritance of mtDNA. As a step
      to elucidate the function of the rep/ori promoter, we have attempted to detect
      transcription-dependent DNA transactions in the mtDNA of a hypersuppressive
      petite mutant. We have examined the mtDNA of the well-characterized petite mutant
      a-1/1R/Z1, whose repeat unit shelters the rep/ori sequence ori1, in strains
      carrying either wild-type or null alleles of the nuclear genes encoding the
      mitochondrial transcription apparatus. Complex DNA transactions were detected
      that take place around GC-cluster C, an evolutionarily conserved GC-rich sequence
      block immediately downstream from the rep/ori promoter. These transactions are
      strictly dependent upon mitochondrial transcription.

PMID- 9566918
TI  - Virus-dependent phosphorylation of the IRF-3 transcription factor regulates
      nuclear translocation, transactivation potential, and proteasome-mediated
      degradation.
AB  - The interferon regulatory factors (IRF) consist of a growing family of related
      transcription proteins first identified as regulators of the alpha beta
      interferon (IFN-alpha/beta) gene promoters, as well as the interferon-stimulated
      response element (ISRE) of some IFN-stimulated genes. IRF-3 was originally
      identified as a member of the IRF family based on homology with other IRF family
      members and on binding to the ISRE of the ISG15 promoter. IRF-3 is expressed
      constitutively in a variety of tissues, and the relative levels of IRF-3 mRNA do
      not change in virus-infected or IFN-treated cells. In the present study, we
      demonstrate that following Sendai virus infection, IRF-3 is posttranslationally
      modified by protein phosphorylation at multiple serine and threonine residues,
      which are located in the carboxy terminus of IRF-3. A combination of IRF-3
      deletion and point mutations localized the inducible phosphorylation sites to the
      region -ISNSHPLSLTSDQ- between amino acids 395 and 407; point mutation of
      residues Ser-396 and Ser-398 eliminated virus-induced phosphorylation of IRF-3
      protein, although residues Ser-402, Thr-404, and Ser-405 were also targets.
      Phosphorylation results in the cytoplasm-to-nucleus translocation of IRF-3, DNA
      binding, and increased transcriptional activation. Substitution of the Ser-Thr
      sites with the phosphomimetic Asp generated a constitutively active form of IRF-3
      that functioned as a very strong activator of promoters containing PRDI-PRDIII or
      ISRE regulatory elements. Phosphorylation also appears to represent a signal for
      virus-mediated degradation, since the virus-induced turnover of IRF-3 was
      prevented by mutation of the IRF-3 Ser-Thr cluster or by proteasome inhibitors.
      Interestingly, virus infection resulted in the association of IRF-3 with the CREB
      binding protein (CBP) coactivator, as detected by coimmunoprecipitation with anti
      CBP antibody, an interaction mediated by the C-terminal domains of both proteins.
      Mutation of residues Ser-396 and Ser-398 in IRF-3 abrogated its binding to CBP.
      These results are discussed in terms of a model in which virus-inducible, C
      terminal phosphorylation of IRF-3 alters protein conformation to permit nuclear
      translocation, association with transcriptional partners, and primary activation
      of IFN- and IFN-responsive genes.

PMID- 9566919
TI  - AP-1 factors play an important role in transformation induced by the v-rel
      oncogene.
AB  - v-rel is the oncogenic member of the Rel/NF-kappaB family of transcription
      factors. The mechanism by which v-Rel induces transformation of avian lymphoid
      cells and fibroblasts is not precisely known. However, most models propose that v
      rel disrupts the normal transcriptional regulatory network. In this study we
      evaluated the role of AP-1 family members in v-Rel-mediated transformation. The
      overexpression of v-Rel, c-Rel, and c-Rel delta resulted in a prolonged elevation
      of c-fos and c-jun expression and in a sustained repression of fra-2 at both the
      mRNA and protein levels in fibroblasts and lymphoid cells. Moreover, the
      transforming abilities of these Rel proteins correlated with their ability to
      alter the expression of these AP-1 factors. v-Rel exhibited the most pronounced
      effect, whereas c-Rel, with poor transforming ability, elicited only moderate
      changes in AP-1 levels. Furthermore, c-Rel delta, which exhibits enhanced
      transforming potential relative to c-Rel, induced intermediate changes in AP-1
      expression. To directly evaluate the role of AP-1 family members in the v-Rel
      transformation process, a supjun-1 transdominant mutant was used. The supjun-1
      mutant functions as a general inhibitor of AP-1 activity by inhibiting AP-1
      mediated transactivation and by reducing AP-1 DNA-binding activity. Coinfection
      or sequential infection of fibroblasts or lymphoid cells with viruses carrying
      rel oncogenes and supjun-1 resulted in a reduction of the transformation
      efficiency of the Rel proteins. The expression of supjun-1 inhibited the ability
      of v-Rel transformed lymphoid cells and fibroblasts to form colonies in soft agar
      by over 70%. Furthermore, the expression of supjun-1 strongly interfered with the
      ability of v-Rel to morphologically transform avian fibroblasts. This is the
      first report showing that v-Rel might execute its oncogenic potential through
      modulating the activity of early response genes.

PMID- 9566920
TI  - Induction of Sp1 in differentiating human embryonal carcinoma cells triggers
      transcription of the fibronectin gene.
AB  - Cells of the human embryonal carcinoma line NEC14 proliferate as densely packed
      clusters consisting of small, polygonal stem cells and do not express a
      detectable level of fibronectin (FN). Upon induction of differentiation by
      treatment with N,N'-hexamethylene bisacetamide (HMBA), the level of FN mRNA
      increased steeply within 24 h and FN began to be accumulated, along with the
      organization of actin filaments in the cells. The FN promoter elements required
      for the activation were analyzed in reference to a cluster of GC boxes by using
      the chloramphenicol acetyltransferase (CAT) gene fused to 5' sequential-deletion
      derivatives of the promoter and promoters carrying base substitutions in the GC
      boxes. Among four GC boxes, GC boxes 2 and 3 had the greatest effect on promoter
      activation, and base substitutions in these GC boxes resulted in 80% reduction in
      promoter activity. The pattern of DNA-protein complex formation with these GC
      boxes changed drastically after induction of differentiation. The extract
      prepared from undifferentiated NEC14 cells formed fast-migrating complexes (UnD
      complexes), while the extract prepared from NEC14 cells treated with HMBA for 24
      h formed slow-migrating complexes containing Sp1. Both complexes were formed
      predominantly with GC box 2. Base substitutions within the GC boxes completely
      abolished the formation of both UnD and Sp1 complexes. Consistent with these
      changes, the Sp1 level increased steeply within 24 h. Induction of Sp1 expression
      in NEC14 cells effectively stimulated the promoter activity of the transfected FN
      promoter-CAT constructs. These results indicate that activation of the FN
      promoter in differentiating NEC14 cells occurs by the steep induction of Sp1,
      which prevents an undifferentiated cell factor from binding to the Sp1 sites.

PMID- 9566921
TI  - A promoter region mutation affecting replication of the Tetrahymena ribosomal DNA
      minichromosome.
AB  - In the ciliated protozoan Tetrahymena thermophila the ribosomal DNA (rDNA)
      minichromosome replicates partially under cell cycle control and is also subject
      to a copy number control mechanism. The relationship between rDNA replication and
      rRNA gene transcription was investigated by the analysis of replication,
      transcription, and DNA-protein interactions in a mutant rDNA, the rmm3 rDNA. The
      rmm3 (for rDNA maturation or maintenance mutant 3) rDNA contains a single-base
      deletion in the rRNA promoter region, in a phylogenetically conserved sequence
      element that is repeated in the replication origin region of the rDNA
      minichromosome. The multicopy rmm3 rDNA minichromosome has a maintenance defect
      in the presence of a competing rDNA allele in heterozygous cells. No difference
      in the level of rRNA transcription was found between wild-type and rmm3 strains.
      However, rmm3 rDNA replicating intermediates exhibited an enhanced pause in the
      region of the replication origin, roughly 750 bp upstream from the rmm3 mutation.
      In footprinting of isolated nuclei, the rmm3 rDNA lacked the wild-type dimethyl
      sulfate (DMS) footprint in the promoter region adjacent to the base change. In
      addition, a DMS footprint in the origin region was lost in the rmm3 rDNA
      minichromosome. This is the first reported correlation in this system between an
      rDNA minichromosome maintenance defect and an altered footprint in the origin
      region. Our results suggest that a promoter region mutation can affect
      replication without detectably affecting transcription. We propose a model in
      which interactions between promoter and origin region complexes facilitate
      replication and maintenance of the Tetrahymena rDNA minichromosome.

PMID- 9566922
TI  - Mutation in the Arabidopsis PASTICCINO1 gene, which encodes a new FK506-binding
      protein-like protein, has a dramatic effect on plant development.
AB  - The pasticcino (pas) mutants of Arabidopsis thaliana are a new class of plant
      developmental mutants; members of this class show ectopic cell proliferation in
      cotyledons, extra layers of cells in the hypocotyl, and an abnormal apical
      meristem. This phenotype is correlated with both cell division and cell
      elongation defects. There are three complementation groups of pas mutants (pas1,
      pas2, and pas3, with, respectively 2, 1, and 4 alleles). Here we describe in more
      detail the pas1-1 allele, which was obtained by insertional mutagenesis. The PAS1
      gene has been cloned and characterized; it encodes an immunophilin-like protein
      similar to the p59 FK506-binding protein (FKBP52). PAS1 is characterized by an
      FKBP-like domain and three tetratricopeptide repeat units. Although the presence
      of immunophilins in plants has already been demonstrated, the pas1-1 mutant
      represents the first inactivation of an FKBP-like gene in plants. PAS1 expression
      is altered in pas1 mutants and in the pas2 and pas3 mutants. The expression of
      the PAS1 gene is increased in the presence of cytokinins, a class of
      phytohormones originally discovered because of their ability to stimulate cell
      division. These results are of particular relevance as they show for the first
      time that an FKBP-like protein plays an important role in the control of plant
      development.

PMID- 9566924
TI  - Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1alpha
      knockout mouse.
AB  - Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1alpha) were produced by
      use of the Cre-loxP recombination system. HNF-1alpha-null mice are viable but
      sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non
      insulin-dependent diabetes mellitus (NIDDM). In contrast to an earlier HNF-1alpha
      null mouse line that had been produced by use of standard gene disruption
      methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P.
      Bach, C. Babinet, and M. Yaniv, Cell 84:575-585, 1996), these mice exhibited no
      increased mortality and only minimal renal dysfunction during the first 6 months
      of development. Both dwarfism and NIDDM are most likely due to the loss of
      expression of insulin-like growth factor I (IGF-I) and lower levels of insulin,
      resulting in stunted growth and elevated serum glucose levels, respectively.
      These results confirm the functional significance of the HNF-1alpha regulatory
      elements that had previously been shown to reside in the promoter regions of both
      the IGF-I and the insulin genes.

PMID- 9566923
TI  - Activation of Rho-dependent cell spreading and focal adhesion biogenesis by the v
      Crk adaptor protein.
AB  - The small GTPase RhoA plays a critical role in signaling pathways activated by
      serum-derived factors, such as lysophosphatidic acid (LPA), including the
      formation of stress fibers in fibroblasts and neurite retraction and rounding of
      soma in neuronal cells. Previously, we have shown that ectopic expression of v
      Crk, an SH2/SH3 domain-containing adapter proteins, in PC12 cells potentiates
      nerve growth factor (NGF)-induced neurite outgrowth and promotes the survival of
      cells when NGF is withdrawn. In the present study we show that, when cultured in
      15% serum or lysophosphatidic acid-containing medium, the majority of v-Crk
      expressing PC12 cells (v-CrkPC12 cells) display a flattened phenotype with broad
      lamellipodia and are refractory to NGF-induced neurite outgrowth unless serum is
      withdrawn. v-Crk-mediated cell flattening is inhibited by treatment of cells with
      C3 toxin or by mutation in the Crk SH2 or SH3 domain. Transient cotransfection of
      293T cells with expression plasmids for p160ROCK (Rho-associated coiled-coil
      containing kinase) and v-Crk, but not SH2 or SH3 mutants of v-Crk, results in
      hyperactivation of p160ROCK. Moreover, the level of phosphatidylinositol-4,5
      bisphosphate is increased in v-CrkPC12 cells compared to the levels in mutant v
      Crk-expressing cells or wild-type cells, consistent with PI(4)P5 kinase being a
      downstream target for Rho. Expression of v-Crk in PC12 cells does not result in
      activation of Rac- or Cdc42-dependent kinases PAK and S6 kinase, demonstrating
      specificity for Rho. In contrast to native PC12 cells, in which focal adhesions
      and actin stress fibers are not observed, immunohistochemical analysis of v
      CrkPC12 cells reveals focal adhesion complexes which are formed at the periphery
      of the cell and are connected to actin cables. The formation of focal adhesions
      correlates with a concomitant upregulation in the expression of focal adhesion
      proteins FAK, paxillin, alpha3-integrin, and a higher-molecular-weight form of
      beta1-integrin. Our results indicate that v-Crk activates the Rho-signaling
      pathway and serves as a scaffolding protein during the assembly of focal
      adhesions in PC12 cells.

PMID- 9566925
TI  - Localization of atypical protein kinase C isoforms into lysosome-targeted
      endosomes through interaction with p62.
AB  - An increasing number of independent studies indicate that the atypical protein
      kinase C (PKC) isoforms (aPKCs) are critically involved in the control of cell
      proliferation and survival. The aPKCs are targets of important lipid mediators
      such as ceramide and the products of the PI 3-kinase. In addition, the aPKCs have
      been shown to interact with Ras and with two novel proteins, LIP (lambda
      interacting protein; a selective activator of lambda/iotaPKC) and the product of
      par-4 (a gene induced during apoptosis), which is an inhibitor of both
      lambda/iotaPKC and zetaPKC. LIP and Par-4 interact with the zinc finger domain of
      the aPKCs where the lipid mediators have been shown to bind. Here we report the
      identification of p62, a previously described phosphotyrosine-independent
      p56(lck) SH2-interacting protein, as a molecule that interacts potently with the
      V1 domain of lambda/iotaPKC and, albeit with lower affinity, with zetaPKC. We
      also show in this study that ectopically expressed p62 colocalizes perfectly with
      both lambda/iotaPKC and zetaPKC. Interestingly, the endogenous p62, like the
      ectopically expressed protein, displays a punctate vesicular pattern and clearly
      colocalizes with endogenous lambda/iotaPKC and endogenous zetaPKC. P62
      colocalizes with Rab7 and partially with lamp-1 and limp-II as well as with the
      epidermal growth factor (EGF) receptor in activated cells, but not with Rab5 or
      the transferrin receptor. Of functional relevance, expression of dominant
      negative lambda/iotaPKC, but not of the wild-type enzyme, severely impairs the
      endocytic membrane transport of the EGF receptor with no effect on the
      transferrin receptor. These findings strongly suggest that the aPKCs are anchored
      by p62 in the lysosome-targeted endosomal compartment, which seems critical for
      the control of the growth factor receptor trafficking. This is particularly
      relevant in light of the role played by the aPKCs in mitogenic cell signaling
      events.

PMID- 9566926
TI  - Selective disruption of genes transiently induced in differentiating mouse
      embryonic stem cells by using gene trap mutagenesis and site-specific
      recombination.
AB  - A strategy employing gene trap mutagenesis and site-specific recombination
      (Cre/loxP) has been used to identify genes that are transiently expressed during
      early mouse development. Embryonic stem cells expressing a reporter plasmid that
      codes for neomycin phosphotransferase and Escherichia coli LacZ were infected
      with a retroviral gene trap vector (U3Cre) 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 two
      selectable marker genes and consequently the expression of beta-galactosidase
      (beta-Gal). As a result, clones in which U3Cre had disrupted genes that were only
      transiently expressed could be selected. Moreover, U3Cre-activating cells
      acquired a cell autonomous marker that could be traced to cells and tissues of
      the developing embryo. Thus, when two of the clones with inducible U3Cre
      integrations were passaged in the germ line, they generated spatial patterns of
      beta-Gal expression.

PMID- 9566928
TI  - Prevention in managed care: joining forces for value and quality. Proceedings of
      a conference. Atlanta, Georgia, USA. January 15-16, 1997.

PMID- 9566929
TI  - Prevention in managed care: joining forces for value and quality. Opening
      plenary.

PMID- 9566930
TI  - Prevention in managed care: joining forces for value and quality. Opening
      plenary.

PMID- 9566931
TI  - Measuring the public's health in an era of accountability: lessons from HEDIS.
      Health Plan Employer Data and Information Set.

PMID- 9566932
TI  - Developing a clinical performance measure.
AB  - BACKGROUND: Clinical performance measurement is an increasingly important way for
      public and private purchasers alike to compare the value of health services
      provided by competing health delivery systems. The widespread use of performance
      measures has increased the demand for development of new measures that cover
      previously unevaluated aspects of care. METHODS: Four steps required to develop a
      clinical performance measure that is suitable for making comparisons among health
      delivery systems are discussed: (1) choosing clinical areas to measure, (2)
      selecting performance indicators within each area, (3) designing specifications
      for consistent implementation of a measure, and (4) evaluating the scientific
      strength of a measure. RESULTS: The application of these steps to developing
      measures of quality for hypertension is provided, with an emphasis on a measure
      of adequacy of control of blood pressure. CONCLUSIONS: Developing useful clinical
      performance measures requires careful attention to methodologic issues. Following
      the steps outlined in this paper should enhance the quality of future measurement
      development.

PMID- 9566927
TI  - Gene amplification in a p53-deficient cell line requires cell cycle progression
      under conditions that generate DNA breakage.
AB  - Amplification of genes involved in signal transduction and cell cycle control
      occurs in a significant fraction of human cancers. Loss of p53 function has been
      proposed to enable cells with gene amplification to arise spontaneously during
      growth in vitro. However, this conclusion derives from studies employing the UMP
      synthesis inhibitor N-phosphonacetyl-L-aspartate (PALA), which, in addition to
      selecting for cells containing extra copies of the CAD locus, enables p53
      deficient cells to enter S phase and acquire the DNA breaks that initiate the
      amplification process. Thus, it has not been possible to determine if gene
      amplification occurs spontaneously or results from the inductive effects of the
      selective agent. The studies reported here assess whether p53 deficiency leads to
      spontaneous genetic instability by comparing cell cycle responses and
      amplification frequencies of the human fibrosarcoma cell line HT1080 when treated
      with PALA or with methotrexate, an antifolate that, under the conditions used,
      should not generate DNA breaks. p53-deficient HT1080 cells generated PALA
      resistant variants containing amplified CAD genes at a frequency of >10(-5). By
      contrast, methotrexate selection did not result in resistant cells at a
      detectable frequency (<10(-9)). However, growth of HT1080 cells under conditions
      that induced DNA breakage prior to selection generated methotrexate-resistant
      clones containing amplified dihydrofolate reductase sequences at a high
      frequency. These data demonstrate that, under standard growth conditions, p53
      loss is not sufficient to enable cells to produce the DNA breaks that initiate
      amplification. We propose that p53-deficient cells must proceed through S phase
      under conditions that induce DNA breakage for genetic instability to occur.

PMID- 9566933
TI  - Partnering to improve infant immunizations: The Arizona Partnership for Infant
      Immunization (TAPII).
AB  - The Arizona Partnership for Infant Immunization (TAPII) is a public-private
      partnership intended to achieve the year 2000 goal of 90% infant immunizations.
      Created in 1992 as a means to develop a statewide approach to improving infant
      immunization rates, TAPII is a broad-based partnership that includes public
      health departments, managed care plans, professional organizations, medical
      organizations, pharmaceutical companies, businesses, the faith community, the
      media, and many others. TAPII's organizational structure includes a steering
      committee and five subcommittees: advocacy and policy, community awareness,
      provider awareness, survey and assessment, and strategic planning. A key
      accomplishment of TAPII has been the development of a statewide infant
      immunization registry known as the Arizona Statewide Immunization Information
      System (ASIIS). This registry will facilitate up-to-date immunizations of
      children and improve statewide immunization assessment capability. Since the
      advent of TAPII, infant immunization rates within private managed care plans have
      increased. However, significant improvement in statewide rates will require long
      term strategic efforts in provider and community awareness and a fully
      operational statewide registry, ASIIS, which is set to begin in January 1998.
      TAPII has been a successful partnership for a number of reasons: private sector
      participation, a single and measurable goal, vision and leadership, a strong
      emphasis on assessment, a broad-based membership, community ownership, Governor's
      Office participation, health plan involvement, and full-time project staffing. As
      resources to improve the health of communities diminish, public-private
      partnerships such as TAPII can effectively consolidate resources and expertise to
      improve the health of populations.

PMID- 9566934
TI  - Cancer screening in HMOs: program development and evaluation.
AB  - INTRODUCTION: In many clinical settings, effective cancer control is hampered by
      barriers related to the acute-care orientation of most medical practices. These
      include: prioritization of medical problems on the basis of urgency; a problem
      oriented medical record that provides no ongoing documentation mechanism for
      cancer screening; conflicting guidelines; and no method for identifying and
      targeting persons who are eligible for screening. In contrast, HMOs are uniquely
      suited to deliver effective cancer control as they have already established many
      of the linkages required for successful primary and secondary prevention.
      METHODS: This paper describes the principles of a population-based approach to
      cancer prevention and draws on the experience of Group Health Cooperative of
      Puget Sound, an HMO in western Washington with more than 20 years' experience in
      prevention and centralized cancer screening. Methods for selecting and
      determining priorities among cancer prevention issues, components of successful
      screening programs, and measures of short- and long-term evaluation are discussed
      through examples of screening for breast, prostate, cervix, and colorectal
      cancers. CONCLUSIONS: HMOs have provided leadership in the integration of health
      services and the promotion of continuity of care. Using a population-based
      approach, cancer prevention programs may be supported by existing automated
      information services to reduce morbidity and mortality through early detection.

PMID- 9566935
TI  - Prevention of work-related disability.
AB  - INTRODUCTION: The cost of work-related injury is large and is rising in many
      states. Managed care providers are being asked to assist with solutions,
      particularly in the area of facilitating return to work. Kaiser Permanente of the
      Northwest responded by developing the Kaiser on-the-job program, which includes
      processes to facilitate the primary, secondary, and tertiary prevention of work
      related disability. METHODS: This paper describes the role that managed care can
      play in the prevention of work-related disability through consultation, training,
      immunization programs, and targeted screening and case management interventions.
      A quality and case management system is described, which gives physicians
      feedback on modified work and time-off authorization by diagnosis. RESULTS: The
      results demonstrate statistically significant decreasing physician-authorized
      average time loss for low back cases from 1991 through 1995 (17.8 disability days
      per case in 1991 and 15 per case in 1995, P = .01). According to Oregon State
      Accident Insurance Fund (SAIF Corporation) data, the Kaiser on-the-job average
      total claims cost was reduced 33% for disabling cases as compared to two other
      health care organizations (P = .002). CONCLUSION: The methods utilized here to
      prevent work-related disability appear effective. They are relevant to many
      managed care program models and their efforts to improve workplace health and
      productivity.

PMID- 9566936
TI  - Comprehensive health data systems spanning the public-private divide: the
      Massachusetts experience.
AB  - As systems of health care delivery have evolved from claims-based fee-for-service
      to capitated or managed care, with its emphasis on cost-effectiveness, quality,
      and performance measurement, some states have begun to experiment with new ways
      to collect, organize, and share health information. In many cases, the drivers of
      these changes have been purchasers of health care, including large and small
      private employers and public agencies such as Medicaid. One of the results of
      these changes is the increased interest in the sharing of health information,
      between health plans and employers, and, in some instances, between private plans
      and public agencies such as public health. Massachusetts, which has one of the
      highest rates of managed care penetration in the United States, has brought
      together the various parties involved in the collection and utilization of health
      information, to craft agreements on standards and protocols that will allow the
      sharing of health data. While much of the activity involves business transactions
      between private sector health plans, the Department of Medical Assistance
      (Medicaid) has joined with its private sector purchasing partners in demanding
      cost-effective, high-quality care; it is these demands that have helped stimulate
      the need to reorganize previously proprietary health information systems. The
      activities of two public-private coalitions, the Massachusetts Healthcare
      Purchaser Group and the Massachusetts Health Data Consortium, have been critical
      in initiating and supporting the complex processes that have led to significant
      changes in state-based systems of health information.

PMID- 9566937
TI  - The role of tobacco intervention in population-based health care: a case study.
AB  - Managed care organizations are in an excellent position to implement population
      based, as well as patient-centered, approaches to reduce behavioral risk factors
      associated with major chronic diseases. Group Health Cooperative of Puget Sound
      employed a population-based model for smoking that contributed to a decrease from
      25% to 15.5% in smoking prevalence in 10 years among its more than 550,000 adult
      enrollees in western Washington. This model may have application to other arenas
      where health systems can support beneficial behavior change.

PMID- 9566938
TI  - Public health, communicable diseases, and managed care: Will managed care improve
      or weaken communicable disease control?
AB  - BACKGROUND: Several changes can be anticipated in the practice of communicable
      disease control as a result of the health care delivery system's transition from
      a predominantly fee-for-service system to a predominantly managed care system.
      These changes will clearly involve clinical services provided by public health
      agencies, such as immunizations and diagnosis and treatment of tuberculosis and
      sexually transmitted diseases, as well as those that do not involve direct
      patient care, such as public health surveillance, disease investigation, outbreak
      control, contact tracing, public health laboratory services, and health
      education. METHODS: In this paper I review the potential impact of managed care
      on each of these areas of communicable disease control and suggest strategies for
      minimizing adverse effects and maximizing potential areas of cooperation.
      RESULTS: Examples of successful strategies include California's Medi-Cal managed
      care expansion, which allows local public health agencies to bill managed care
      organizations for the sexually transmitted disease, immunization, and
      confidential HIV services they provide to managed care beneficiaries. A different
      strategy is illustrated by the Pacific Business Group on Health, an employer
      based purchasing group, that uses purchasing power to standardize the clinical
      preventive services benefit across all plans with which it contracts and to
      promote immunization goals. CONCLUSION: This analysis and these examples suggest
      that the emergence of managed care as the predominant form of health care
      financing and delivery in the United States offers an important opportunity for
      public health.

PMID- 9566939
TI  - School and adolescent health and managed care.
AB  - BACKGROUND: The current rapid expansion of managed care in the United States
      creates opportunities and dilemmas for improving adolescent health. Collaboration
      among managed care organizations, schools, and public health agencies
      increasingly is critical to adequately address the health needs of youth and to
      increase adolescent access to effective prevention services. RESULTS: This paper
      discusses exigencies that schools and adolescent health care providers are
      facing, the relationship of managed care to public health, and the implications
      of managed care for adolescent health promotion. To illustrate some of these
      issues, we describe a unique collaborative relationship between HealthPartners, a
      managed care organization in Minneapolis, Minnesota, and Health Start, a
      nonprofit organization based in St. Paul, Minnesota, that manages the eight
      school-based health centers in the St. Paul Public Schools.

PMID- 9566940
TI  - Negotiating the new health system: purchasing publicly accountable managed care.
AB  - The transformation to managed care is one of the most important and complex
      changes ever to take place in the American health system. One key aspect of this
      transformation is its implications for public health policy and practice. Both
      public and private buyers purchase managed care; increasingly, public programs
      that used to act as their own insurers (i.e., Medicare, Medicaid and CHAMPUS) are
      purchasing large quantities of managed care insurance from private companies. The
      transformation to managed care is altering the manner in which public health
      policy makers conceive of and carry out public health activities (particularly
      activities that involve the provision of personal health services). The degree to
      which managed care changes public health and in turn is altered by public health
      will depend in great measure on the extent to which public and private policy
      makers understand the implications of their choices for various aspects of public
      health and take steps to address them. Because both publicly and privately
      managed care arrangements are relatively deregulated, much of the dialogue
      between public health and managed care purchasers can be expected to take place
      within the context of the large service agreements that are negotiated between
      buyers and sellers of managed care products. This is particularly true for
      Medicaid because of the importance of Medicaid coverage, payment and access
      policies to public health policy makers, and because of the public nature of the
      Medicaid contracting process. A nationwide study of Medicaid managed care
      contracts offers the first detailed analysis of the content and structure of
      managed care service agreements and the public health issues they raise. Four
      major findings emerge from a review of the contracts. First, most of the
      agreements fail to address key issues regarding which Medicaid-covered services
      and benefits are the contractor's responsibility and which remain the residual
      responsibility of the state agency. Second, most contracts fail to address the
      legal and structural issues arising from the relationship between the managed
      care service system and the public health system, including such key matters as
      access to care for communicable diseases and contractors' relationship to state
      public health laboratories. Third, many contracts are silent on health agencies'
      access to data for surveillance and community health measurement purposes.
      Finally, many contracts may be developed with only a limited understanding of the
      key public health-related issues facing the community from which the members will
      be drawn. The CDC and state and local public health agencies must expand their
      activities in the area of managed care contract specifications. For several years
      the CDC has been involved in an ongoing effort to develop quality of care
      measures to be collected from all companies through the HEDIS process. As
      important as this effort is, it represents only an attempt to measure what
      managed care does rather than an a priori effort to shape the underlying policy
      and organizational structure of managed care itself. Integrating managed care
      with public health policy will require this type of affirmative effort with both
      Medicaid agencies as well as other managed care purchasers.

PMID- 9566941
TI  - Building public health goals into the purchasing process: the Missouri Medicaid
      agency as purchaser.
AB  - INTRODUCTION: As managed care radically changes the medical care environment,
      public health leaders are under increasing pressure to focus more on core public
      health functions and less on personal health services. As public health re
      evaluates its key strategies, it can take advantage of its strategic role in
      purchasing medical care to forge new partnerships that benefit its constituents.
      METHODS: Specific roles for public health in medical care purchasing are
      discussed. The state of Missouri is used as an example of successful strategies
      for positioning public health as a leader in the managed care environment. Key
      strategies include increasing influence in contracting; selecting and reporting
      of key health status indicators; promoting use of population-based data files;
      taking leadership roles in government-sponsored insurance programs; and assuring
      stability of critical health conditions during managed care transitions.
      CONCLUSION: Public health has unprecedented opportunities to develop new methods
      for improving health status. Public health's well-developed scientific principles
      and methods, combined with strategic leadership, will position the discipline in
      the forefront of the dialogue about our nation's health system into the next
      century.

PMID- 9566942
TI  - Building public health goals into the purchasing process: managed care
      perspective.
AB  - Public health and managed care organizations are increasingly developing
      contracts for the care of Medicaid patients. Factors leading to this relationship
      include increasing managed care interest in returning to the concept of "health
      maintenance" and population medicine, and the decreasing funding available to
      public health. Each partner has strengths that can be utilized in such
      relationships. Obstacles exist in the development of this relationship, including
      the already considerable reporting burdens on managed care organizations and
      issues surrounding the contracts and delegation of services. Despite this there
      are many examples of public health managed care partnerships.

PMID- 9566943
TI  - Preventing childhood lead poisoning: the challenge of change.
AB  - Because of their rapid growth, immature biologic systems, and their developmental
      characteristics, children are uniquely vulnerable to exposure to environmental
      hazards. One of these is lead. Revised lead screening guidelines, published by
      the Centers for Disease Control and Prevention in Fall 1997, no longer advocate
      universal screening in some places. These guidelines will (1) require new
      policies from local public health agencies, (2) require new approaches for
      clinicians and managed care organizations, especially those with Medicaid
      recipient enrollees, to conduct screening of children who may be at risk for
      exposure to lead, (3) offer new challenges for environmental follow-up to
      children identified with elevated lead levels, and (4) provide opportunities for
      collaboration between managed care and public health agencies.

PMID- 9566944
TI  - Diabetes mellitus and asthma: "twin" challenges for public health and managed
      care systems.
AB  - Many changes are rapidly occurring in and to health care systems in the United
      States. These changes reflect fundamental concerns about issues of access,
      quality of care, and cost of health services. The emergence of chronic diseases,
      the importance of economic considerations in health decisions; and the proper
      role of managed care organizations (MCOs) are of particular significance.
      Diabetes mellitus (DM) and asthma are two conditions that are frequently used as
      "model diseases" to study the impact of these changes. In spite of apparent
      differences between asthma and DM, there are, in fact, many important
      commonalities that explain the attention being directed to these diseases. In
      considering basic tenets, objectives, and approaches, MCOs and public health
      systems also have very common interests and characteristics. In understanding the
      impact of the many emerging health care concepts and approaches on DM and asthma,
      public health and MCOs can be better positioned not only to understand each
      other, but also to subsequently address other important chronic diseases, injury
      related disorders, and behavioral/emotional conditions in an effective and
      efficient manner.

PMID- 9566945
TI  - Community solutions to violence: a Minnesota managed care action plan.
AB  - Reducing violence is a critical health and economic priority. In Minnesota, as in
      other parts of the United States, violence is increasingly viewed as a public
      health problem. Helping people work together to prevent violence is one way that
      managed care organizations are collaborating with public health to improve the
      health of communities. In 1994, Blue Cross and Blue Shield of Minnesota worked
      with community organizations to develop The Minnesota Action Plan to End Gun
      Violence, a broad-based solution to a community problem: violence in Minnesota.
      The goal of this initiative was to develop grassroots solutions to violence and
      to inspire community members to take action. Outcomes of the initiative included:
      participation by over 1,000 Minnesotans in 12 community violence prevention
      forums; a widely distributed action plan; Students Stop Guns, a school-based
      intervention to keep Minnesota schools gun-free; the Governor's Task Force on
      Violence as a Public Health Problem, which led to a commitment of resources to
      prevent violence and respond to the victims and consequences of violence, and the
      Health Care Coalition on Violence, to institutionalize strategies within the
      Minnesota health care environment. The project's qualitative evaluation resulted
      in lessons and advice on how to execute a collaborative health improvement
      initiative. These lessons have been widely shared with Minnesota community health
      advocates.

PMID- 9566946
TI  - Prevention in managed care: joining forces for value and quality. Closing
      plenary.

PMID- 9566947
TI  - HCFA's influence as the nation's largest purchaser of health services.

PMID- 9566948
TI  - Prevention, public health, and managed care: obstacles and opportunities.

PMID- 9566949
TI  - Expression of Smad1 and Smad2 during embryogenesis suggests a role in organ
      development.
AB  - Smad proteins are intracellular signalling molecules and putative transcription
      factors that transduce signals elicited by members of the transforming growth
      factor beta (TGF-beta) superfamily. By comparing the expression of Smad1 and
      Smad2 during embryonic development, we show that mRNAs of both Smad isoforms are
      present in a variety of tissues. The major sites of expression of both Smads can
      be correlated with the expression domains of several members of the TGF-beta
      superfamily. Our expression data suggest that Smad proteins are involved in organ
      development, particularly that of organs arising from mesenchymal-epithelial
      interactions. A second site of strong expression is the central nervous system.
      Transcriptional control mediated by Smad1 and Smad2, therefore, may exert an
      important function in differentiation processes of embryonic development that are
      controlled by ligands of the TGF-beta superfamily.

PMID- 9566950
TI  - Embryonic implantation in galectin 1/galectin 3 double mutant mice.
AB  - Galectin 1 and galectin 3 are first expressed in the trophectoderm cells of the
      implanting embryo and have been implicated in the process of implantation.
      However, we had previously shown that the lack of galectin 1 in galectin 1 null
      mutant mice is compatible with implantation. In this study, we describe the
      generation of galectin 3 null mutant mice and show that they are viable and have
      no overt abnormalities. The importance of galectin 1 and galectin 3 in
      implantation was assessed by obtaining double mutant mice [gal1 -/-; gal3 -/-].
      We find that implantation can still occur in the absence of both galectin 1 and
      galectin 3. However, we show that galectin 5, a third member of this gene family,
      is also present in the blastocyst at the time of implantation.

PMID- 9566951
TI  - New cell surface marker of the rat floor plate and notochord.
AB  - Regionally expressed cell surface molecules are thought to mediate contact
      dependent interactions that regulate pattern formation and axon pathfinding in
      the developing vertebrate central nervous system (CNS). We recently isolated
      monoclonal antibody (mAb) CARO 2 through a screen for positional markers in the
      developing rat CNS. Between embryonic day (E)11.5 and E13, mAb CARO 2
      specifically labels both the floor plate and notochord in the developing spinal
      cord. In contrast to the distribution of several well-characterized ventral
      midline markers, mAb CARO 2 labeling is restricted to the apical portion of the
      floor plate and the outer surface of the notochord. The anterior limit of mAb
      CARO 2 immunoreactivity corresponds to the midbrain/hindbrain border. Floor plate
      labeling persists throughout embryogenesis, whereas notochord labeling is not
      detectable after E13. During later stages of embryonic development (E16-E20)
      apically restricted floor plate labeling is present only in the rostral spinal
      cord. In postnatal rats, mAb CARO immunoreactivity is not present in any region
      of the CNS. Immunoblot analyses show that mAb CARO 2 recognizes an epitope on a
      28-kD protein that is enriched in the floor plate, transiently expressed during
      embryogenesis, and membrane-associated. Consistent with the latter result, mAb
      CARO 2 labels the surfaces of floor plate cells. These findings suggest that the
      CARO 2 antigen is a new cell surface marker of the floor plate and notochord
      which may participate in neural cell patterning and/or axon guidance in the
      developing rat spinal cord.

PMID- 9566952
TI  - Ontogeny of the opioid growth factor, [Met5]-enkephalin, preproenkephalin gene
      expression, and the zeta opioid receptor in the developing and adult aorta of
      rat.
AB  - Opioid peptides are known to play a role in the function of the mammalian
      cardiovascular system in the newborn. To learn about mechanisms underlying the
      morphogenesis of the developing vasculature and the principles contributing to
      the organization and maintenance of adult blood vessels, we have investigated the
      expression of the opioid growth factor (OGF), [Met5]-enkephalin, and its
      receptor, zeta. Moreover, gene expression for preproenkephalin mRNA, which
      encodes OGF, was studied to determine the source(s) of this inhibitory growth
      factor. By using immunocytochemistry, both OGF and the zeta opioid receptor were
      detected at embryonic day (E) 16 in the mesenchymal cells of the aortic wall.
      Staining appeared to be abundant in endothelial cells, smooth muscle cells, and
      fibroblasts at E20 and in the neonate. Immunoreactivity was noted to decrease
      progressively from day 5 to 10, but by weaning (day 21) and continuing into
      adulthood intense staining for both the peptide and receptor were observed.
      Preproenkephalin mRNA was detected throughout the aortic wall at E16, and the
      number of silver grains increased up today. Message was progressively reduced at
      days 5, 10, and 21, but signal in the adult aorta was comparable to that observed
      at day 5. These results indicate that components related to an endogenous opioid
      system regulating growth are present in the embryo, display a distinct spatial
      and temporal pattern of ontogeny, and persist into adulthood. In addition, these
      data indicate that OGF is an autocrine produced growth factor that is related to
      the emergence of vascular architecture and the maintenance of homeostasis in
      blood vessels.

PMID- 9566953
TI  - Cadherin-6 in the developing mouse brain: expression along restricted connection
      systems and synaptic localization suggest a potential role in neuronal circuitry.
AB  - Multiple subtypes of the cadherin homophilic cell-cell adhesion molecule are
      expressed differentially in developing and mature brains, each being expressed in
      restricted neuronal groups. Cadherin-6 (cad6) is one of such cadherins. Recent
      studies of cad6 mRNA expression in the postnatal mouse forebrain showed that it
      occurs in neurons constituting a specific subset of thalamocortical connections.
      Here we analyzed the localization of cad6 mRNA as well as its protein in the
      entire central nervous system and also in cranial ganglia of mice at late
      embryonic to postnatal stages. Our results showed that cad6 is expressed by a
      limited population of neurons or their precursors, which are synaptically
      connected to one another, throughout the perinatal stages, and that this
      expression delineates restricted neuronal circuits from the central to peripheral
      nervous systems, which include subpathways of the auditory, somatosensory,
      solitary, vestibular, and olivocerebellar systems. cad6 proteins were detected in
      these cad6 mRNA-positive neurons on the surface of their cell bodies or dendrites
      as well as in the cytoplasm. Confocal microscopic analysis revealed that the cad6
      protein distribution overlapped that of synaptotagmin in synapse forming areas,
      suggesting that homotypic cad6 interactions are involved in synaptic connections
      between neurons expressing this protein. These findings support the idea that
      cadherin-mediated cell-cell adhesions take part in specific interneuronal
      connections.

PMID- 9566954
TI  - zALK-8, a novel type I serine/threonine kinase receptor, is expressed throughout
      early zebrafish development.
AB  - Here, we report the isolation and characterization of zebrafish activin receptor
      like kinase-8 (zALK-8), a novel type I serine/threonine (ser/thr) kinase receptor
      of the transforming growth factor beta (TGF-beta) family. zALK-8 is novel, in
      that it contains an extracellular domain that is quite distinct from that of
      previously identified ALK receptors 1 through 7. Analysis of the predicted amino
      acid sequence of the 506 amino acid zALK-8 receptor reveals an ser/thr kinase
      domain characteristic of type I TGF-beta family member receptors. zALK-8,
      therefore, is a traditional type I ser/thr kinase receptor of the TGF-beta
      family, but it may exhibit novel ligand-binding activities. The developmental
      expression of zALK-8 mRNA was examined by wholemount in situ hybridization
      analysis using a probe from the 3'-untranslated sequence of zALK-8, which does
      not cross react with other members of the highly conserved TGF-beta receptor
      family. zALK-8 mRNA is present as a maternal message that is expressed
      ubiquitously before the start of zygotic transcription. By 16 hr
      postfertilization (hpf), zALK-8 mRNA is still expressed fairly evenly throughout
      the embryo. In 24-hpf embryos, zALK-8 mRNA is expressed predominantly in the
      developing eye and neural structures. By 48 hpf, zALK-8 mRNA is faintly
      detectable as a diffuse signal throughout the head. zALK-8 mRNA is not detectable
      by this method in 72-hpf or 96-hpf embryos. Northern analysis of zALK-8 mRNA in
      poly(A+) mRNA isolated from 6-9 hpf embryos detects a major transcript of 3.6 kb
      and a minor transcript of 4.3 kb. zALK-8 mRNA expression correlates well with
      known functions of TGF-beta family members as early axial patterning and mesoderm
      inducing growth factors and as potent growth and differentiation factors in
      craniofacial development.

PMID- 9566955
TI  - Developmentally regulated expression and localization of fibroblast growth factor
      receptors in the human muscle.
AB  - Fibroblast growth factors (FGFs) are believed to play a key role in tissue
      differentiation and maturation. Thus, the expression of the four members of the
      high-affinity tyrosine kinase FGF receptor family (FGFRs) and of the low-affinity
      heparan sulphate proteoglycan binding sites, syndecan-1 and perlecan, was studied
      in the human skeletal muscle during development. Northern blot analysis
      demonstrated a developmentally regulated expression of the mRNAs for FGFR-1, FGFR
      3, FGFR-4, whereas only traces of FGFR-2 mRNA were found. Each receptor type had
      a different developmental pattern, suggesting an independent regulation. Signal
      for FGFR-3 was retained only in the adult muscle. Among the low-affinity FGF
      binding sites, perlecan was absent, whereas RNA transcript for syndecan-1 peaked
      at week 13 of gestation, after which a significant decrease was observed.
      Immunohistochemistry for FGFRs revealed that their localization changed with
      muscle maturation. At early embryonic stages, FGFR-3 and FGFR-4 had a scattered
      distribution in the tissue, and FGFR-1 was found on myotube and myofiber plasma
      membranes. At later stages, FGFR-1 positivity decreased and was found in a few
      areas of the muscle, FGFR-3 was concentrated in the nuclei of some, but not all,
      muscle fibers, and FGFR-4 maintained an association with plasma membrane. In
      adult tissue, weak positivity for FGFR-3 and FGFR-4 was observed in the
      connective tissue only. When immunocytochemistry was performed on human fetal
      myoblasts in culture, confocal microscope analysis revealed a nonhomogeneous cell
      membrane distribution of FGFRs. Taken together, the data strongly suggest that
      developmentally regulated expression and cell distribution of FGFRs play a role
      during muscle maturation.

PMID- 9566956
TI  - Malformation of trachea and pelvic region in goosecoid mutant mice.
AB  - The homeobox gene goosecoid is expressed in the Spemann organizer tissue of
      gastrulating vertebrate embryos, and in the craniofacial region and appendicular
      skeleton during organogenesis. The goosecoid knockout mutant mouse revealed
      defects related to the second phase of expression. Here we describe new
      expression sites in the developing trachea and external genitalia, and in the
      developing shoulder and hip joint with their associated ligaments and muscles. We
      show that mutant mice display abnormalities in the forming trachea and
      appendicular skeleton related to these sites of gene expression. In addition, we
      discuss evidence for the existence of at least three goosecoid genes in
      vertebrates, which may account for the lack of a defect of axial patterning in
      goosecoid mutant mice.

PMID- 9566957
TI  - Role of differential cell proliferation in the tail bud in aberrant mouse
      neurulation.
AB  - In the mouse mutant curly tail, the phenotypes spina bifida and curled tail
      result from a delay in closure of the posterior neuropore (PNP). At the
      developmental stage when this delay can first be recognized, the caudal region of
      the embryo demonstrates a transiently enhanced curvature of the body axis which
      likely inhibits elevation, convergence, and fusion of the neural folds. The
      enhanced curvature is thought to be the result of a decreased proliferation in
      the ventrally located gut endoderm and notochord, together with a normal
      proliferation of the overlying neuroepithelium of the PNP. However, the
      proliferation defect and the enhanced curvature were originally demonstrated at
      the same developmental stage, while it is expected that reduced proliferation
      should precede enhanced curvature and delayed PNP closure. The caudal region
      originates from the tail bud and we therefore propose that the enhanced curvature
      is induced by a disturbed dorso-ventral proliferation pattern in the tail bud.
      Using flow cytometry, proliferation patterns were determined separately for the
      dorsal and ventral halves of the tail bud of curly tail and of control embryos as
      well as of recombinant embryos having the curly tail phenotype with a genetic
      background which is matched to the BALB/c control strain. In general, it appeared
      that about half of the cell cycle duration in tail bud cells was occupied by S
      phase, about 40% by G0/G1 and the rest by G2/M. For the control embryos, no dorso
      ventral differences in relative phase duration were demonstrated. However, curly
      tail and recombinant embryos at the 21-25 somite stage, prior to the onset of
      enhanced curvature, exhibited ventrally a higher proportion of G0/G1 phase cells
      than dorsally, and a complementary relationship for S phase cells. We interpret
      these observations as indicating a prolonged G1 phase at the ventral side of the
      tail bud, resulting in a prolongation of the cell cycle and thus a decreased
      proliferation. In 26-30 somite stage embryos, prior to the normalization of
      curvature in curly tail embryos, the dorso-ventral proliferation balance was re
      established. We conclude that a reduced proliferation in the ventral part of the
      tail bud of the curly tail embryo precedes both the onset of enhanced curvature
      and the previously observed reduction in proliferation of the hindgut and
      notochord, and is a likely candidate for an early event in the pathogenetic
      sequence leading to the curly tail phenotype.

PMID- 9566958
TI  - Thrombospondins in early Xenopus embryos: dynamic patterns of expression suggest
      diverse roles in nervous system, notochord, and muscle development.
AB  - The thrombospondins (TSPs) are a family of extracellular matrix (ECM)
      glycoproteins that modulate many cell behaviors including adhesion, migration,
      and proliferation. Here we report the molecular cloning of the Xenopus homologs
      of TSP-1 and TSP-3, and the developmental patterns of expression of Xenopus TSP
      1, TSP-3, and TSP-4 mRNAs. Xenopus TSP-1 and TSP-3 protein sequences each share
      approximately 80% amino acid identity with their mammalian counterparts. TSP-1
      mRNAs are detectable at low levels in fertilized eggs indicating that this TSP is
      a maternally deposited transcript. Zygotic expression of TSP-1, TSP-3, and TSP-4
      begins at the end of gastrulation and transcripts encoding each protein
      accumulate through the tadpole stages of development. Whole mount in situ
      hybridizations reveal that each TSP mRNA is localized in the embryo with
      distinct, developmentally regulated patterns of expression. TSP-1 mRNAs are
      detected in a wide range of tissues including the floor plate of the neural tube,
      epidermis, somites, notochord and, most notably, alternating rhombomeres.
      Transcripts encoding TSP-3 are expressed in the notochord, floor plate, sensorial
      layer of the epidermis and sensory epithelia. TSP-4 mRNAs are restricted to
      somitic mesoderm and skeletal muscle. These data suggest that the TSPs represent
      a functionally diverse family of ECM proteins with tissue-specific functions
      during embryogenesis.

PMID- 9566959
TI  - NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved
      in neuronal differentiation.
AB  - The nuclear matrix is defined as the insoluble framework of the nucleus and has
      been implicated in the regulation of gene expression, the cell cycle, and nuclear
      structural integrity via linkage to intermediate filaments of the cytoskeleton.
      We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted
      protein/brain), which contains two major structural elements: a BTB domain-like
      structure in the predicted NH2 terminus, and a "kelch motif" in the predicted
      COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human
      fetal and adult brain with minor expression in kidney and pancreas. During mouse
      embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The
      NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary
      astrocytes. NRP/B expression was upregulated during the differentiation of murine
      Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these
      cells augmented neuronal process formation. Treatment with antisense NRP/B
      oligodeoxynucleotides inhibited the neurite development of rat primary
      hippocampal neurons as well as the neuronal process formation during neuronal
      differentiation of PC-12 cells. Since the hypophosphorylated form of
      retinoblastoma protein (p110(RB)) is found to be associated with the nuclear
      matrix and overexpression of p110(RB) induces neuronal differentiation, we
      investigated whether NRP/B is associated with p110(RB). Both in vivo and in vitro
      experiments demonstrate that NRP/B can be phosphorylated and can bind to the
      functionally active hypophosphorylated form of the p110(RB) during neuronal
      differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our
      studies indicate that NRP/B is a novel nuclear matrix protein, specifically
      expressed in primary neurons, that interacts with p110(RB) and participates in
      the regulation of neuronal process formation.

PMID- 9566960
TI  - Rvs161p interacts with Fus2p to promote cell fusion in Saccharomyces cerevisiae.
AB  - FUS7 was previously identified by a mutation that causes a defect in cell fusion
      in a screen for bilateral mating defects. Here we show that FUS7 is allelic to
      RVS161/END6, a gene implicated in a variety of processes including viability
      after starvation, endocytosis, and actin cytoskeletal organization. Two lines of
      evidence indicate that RVS161/END6's endocytic function is not required for cell
      fusion. First, several other endocytic mutants showed no cell fusion defects.
      Second, we isolated five function-specific alleles of RVS161/FUS7 that were
      defective for endocytosis, but not mating, and three alleles that were defective
      for cell fusion but not endocytosis. The organization of the actin cytoskeleton
      was normal in the cell fusion mutants, indicating that Rvs161p's function in cell
      fusion is independent of actin organization. The three to fourfold induction of
      RVS161 by mating pheromone and the localization of Rvs161p-GFP to the cell fusion
      zone suggested that Rvs161p plays a direct role in cell fusion. The phenotypes of
      double mutants, the coprecipitation of Rvs161p and Fus2p, and the fact that the
      stability of Fus2p was strongly dependent on Rvs161p's mating function lead to
      the conclusion that Rvs161p is required to interact with Fus2p for efficient cell
      fusion.

PMID- 9566961
TI  - Identification of two regions in apolipoprotein B100 that are exposed on the
      cytosolic side of the endoplasmic reticulum membrane.
AB  - Protease protection assays of apolipoprotein B100 (apoB) in digitonin
      permeabilized HepG2 cells indicated that multiple domains of apoB are exposed to
      the cytosol through an extensive portion of the secretory pathway. The
      intracellular orientation of apoB in the secretory pathway was confirmed by
      immunocytochemistry using antibodies recognizing specific domains of apoB in
      streptolysin-O (STP-O)- and saponin-permeabilized HepG2 cells. Lumenal epitopes
      on marker proteins in secretory pathway compartments (p63, p53, and
      galactosyltransferase) were not stained by antibodies in STP-O-treated cells, but
      were brightly stained in saponin-treated cells, confirming that internal
      membranes were not perforated in STP-O-treated cells. An anti-apoB peptide
      antibody (B4) recognizing amino acids 3221-3240 caused intense staining in close
      proximity to the nuclear membrane, and less intensely throughout the secretory
      pathway in STP-O-permeabilized cells. Staining with this antibody was similar in
      STP-O- and saponin-treated cells, indicating that this epitope in apoB is exposed
      to the cytosol at the site of apoB synthesis and throughout most of the remaining
      secretory pathway. Similar results indicating a cytosolic orientation were
      obtained with monoclonal antibody CC3.4, which recognizes amino acids 690-797 (79
      91 kD) in apoB. Two polyclonal antibodies made to human LDL and two monoclonal
      antibodies recognizing amino acids 1878-2148 (D7.2) and 3214-3506 (B1B6) in apoB
      did not produce a strong reticular signal for apoB in STP-O-treated cells. The
      anti-LDL and B1B6 antibodies produced almost identical punctate patterns in STP-O
      treated cells that overlapped with LAMP-1, a membrane marker for lysosomes. These
      observations suggest that the B1B6 epitope of apoB is exposed on the surface of
      the lysosome. The results identify two specific regions in apoB that are exposed
      to the cytosol in the secretory pathway.

PMID- 9566962
TI  - Targeting of protein kinase Calpha to caveolae.
AB  - Previously, we showed caveolae contain a population of protein kinase Calpha
      (PKCalpha) that appears to regulate membrane invagination. We now report that
      multiple PKC isoenzymes are enriched in caveolae of unstimulated fibroblasts. To
      understand the mechanism of PKC targeting, we prepared caveolae lacking PKCalpha
      and measured the interaction of recombinant PKCalpha with these membranes.
      PKCalpha bound with high affinity and specificity to caveolae membranes. Binding
      was calcium dependent, did not require the addition of factors that activate the
      enzyme, and involved the regulatory domain of the molecule. A 68-kD PKCalpha
      binding protein identified as sdr (serum deprivation response) was isolated by
      interaction cloning and localized to caveolae. Antibodies against sdr inhibited
      PKCalpha binding. A 100-amino acid sequence from the middle of sdr competitively
      blocked PKCalpha binding while flanking sequences were inactive. Caveolae appear
      to be a membrane site where PKC enzymes are organized to carry out essential
      regulatory functions as well as to modulate signal transduction at the cell
      surface.

PMID- 9566963
TI  - In polarized MDCK cells basolateral vesicles arise from clathrin-gamma-adaptin
      coated domains on endosomal tubules.
AB  - Human transferrin receptors (TR) and receptors for polymeric immunoglobulins
      (pIgR) expressed in polarized MDCK cells maintain steady-state, asymmetric
      distributions on the separate basolateral and apical surfaces even though they
      are trafficking continuously into and across these cells. The intracellular
      mechanisms required to maintain these asymmetric distributions have not been
      located. Here we show that TR and pIgR internalize from both surfaces to a common
      interconnected endosome compartment that includes tubules with buds coated with
      clathrin lattices. These buds generate vesicles that carry TR to the basolateral
      border. The lattices contain gamma-adaptin and are dispersed by treatment with
      brefeldin A (BFA). Since BFA treatment abrogates the vectorial trafficking of TR
      in polarized MDCK cells, we propose that the clathrin-coated domains of the
      endosome tubules contain the polarized sorting mechanism responsible for their
      preferential basolateral distribution.

PMID- 9566964
TI  - Peroxisome degradation by microautophagy in Pichia pastoris: identification of
      specific steps and morphological intermediates.
AB  - We used the dye N-(3-triethylammoniumpropyl)-4-(p-diethylaminophenylhexatrienyl )
      pyridinium dibromide (FM4-64) and a fusion protein, consisting of the green
      fluorescent protein appended to the peroxisomal targeting signal, Ser-Lys-Leu
      (SKL), to label the vacuolar membrane and the peroxisomal matrix, respectively,
      in living Pichia pastoris cells and followed by fluorescence microscopy the
      morphological and kinetic intermediates in the vacuolar degradation of
      peroxisomes by microautophagy and macroautophagy. Structures corresponding to the
      intermediates were also identified by electron microscopy. The kinetics of
      appearance and disappearance of these intermediates is consistent with a
      precursor-product relationship between intermediates, which form the basis of a
      model for microautophagy. Inhibitors affecting different steps of microautophagy
      did not impair peroxisome delivery to the vacuole via macroautophagy, although
      inhibition of vacuolar proteases affected the final vacuolar degradation of green
      fluorescent protein (S65T mutant version [GFP])-SKL via both autophagic pathways.
      P. pastoris mutants defective in peroxisome microautophagy (pag mutants) were
      isolated and characterized for the presence or absence of the intermediates.
      These mutants, comprising 6 complementation groups, support the model for
      microautophagy. Our studies indicate that the microautophagic degradation of
      peroxisomes proceeds via specific intermediates, whose generation and/or
      processing is controlled by PAG gene products, and shed light on the poorly
      understood phenomenon of peroxisome homeostasis.

PMID- 9566965
TI  - Folding of insulin receptor monomers is facilitated by the molecular chaperones
      calnexin and calreticulin and impaired by rapid dimerization.
AB  - Many complex membrane proteins undergo subunit folding and assembly in the ER
      before transport to the cell surface. Receptors for insulin and insulin-like
      growth factor I, both integral membrane proteins and members of the family of
      receptor tyrosine kinases (RTKs), are unusual in that they require
      homodimerization before export from the ER. To better understand chaperone
      mechanisms in endogenous membrane protein assembly in living cells, we have
      examined the folding, assembly, and transport of the human insulin receptor
      (HIR), a dimeric RTK. Using pulse-chase labeling and nonreducing SDS-PAGE
      analysis, we have explored the molecular basis of several sequential maturation
      steps during receptor biosynthesis. Under normal growth conditions, newly
      synthesized receptor monomers undergo disulfide bond formation while associated
      with the homologous chaperones calnexin (Cnx) and calreticulin (Crt). An
      inhibitor of glucose trimming, castanospermine (CST), abolished binding to
      Cnx/Crt but also unexpectedly accelerated receptor homodimerization resulting in
      misfolded oligomeric proreceptors whose processing was delayed and cell surface
      expression was also decreased by approximately 30%. Prematurely-dimerized
      receptors were retained in the ER and more avidly associated with the heat shock
      protein of 70 kD homologue binding protein. In CST-treated cells, receptor
      misfolding followed disordered oligomerization. Together, these studies
      demonstrate a chaperone function for Cnx/Crt in HIR folding in vivo and also
      provide evidence that folding efficiency and homodimerization are
      counterbalanced.

PMID- 9566967
TI  - The mammalian gamma-tubulin complex contains homologues of the yeast spindle pole
      body components spc97p and spc98p.
AB  - gamma-Tubulin is a universal component of microtubule organizing centers where it
      is believed to play an important role in the nucleation of microtubule
      polymerization. gamma-Tubulin also exists as part of a cytoplasmic complex whose
      size and complexity varies in different organisms. To investigate the composition
      of the cytoplasmic gamma-tubulin complex in mammalian cells, cell lines stably
      expressing epitope-tagged versions of human gamma-tubulin were made. The epitope
      tagged gamma-tubulins expressed in these cells localize to the centrosome and are
      incorporated into the cytoplasmic gamma-tubulin complex. Immunoprecipitation of
      this complex identifies at least seven proteins, with calculated molecular
      weights of 48, 71, 76, 100, 101, 128, and 211 kD. We have identified the 100- and
      101-kD components of the gamma-tubulin complex as homologues of the yeast spindle
      pole body proteins Spc97p and Spc98p, and named the corresponding human proteins
      hGCP2 and hGCP3. Sequence analysis revealed that these proteins are not only
      related to their respective homologues, but are also related to each other. GCP2
      and GCP3 colocalize with gamma-tubulin at the centrosome, cosediment with gamma
      tubulin in sucrose gradients, and coimmunoprecipitate with gamma-tubulin,
      indicating that they are part of the gamma-tubulin complex. The conservation of a
      complex involving gamma-tubulin, GCP2, and GCP3 from yeast to mammals suggests
      that structurally diverse microtubule organizing centers such as the yeast
      spindle pole body and the animal centrosome share a common molecular mechanism
      for microtubule nucleation.

PMID- 9566968
TI  - Xgrip109: a gamma tubulin-associated protein with an essential role in gamma
      tubulin ring complex (gammaTuRC) assembly and centrosome function.
AB  - Previous studies indicate that gamma tubulin ring complex (gammaTuRC) can
      nucleate microtubule assembly and may be important in centrosome formation.
      gammaTuRC contains approximately eight subunits, which we refer to as Xenopus
      gamma ring proteins (Xgrips), in addition to gamma tubulin. We found that one
      gammaTuRC subunit, Xgrip109, is a highly conserved protein, with homologues
      present in yeast, rice, flies, zebrafish, mice, and humans. The yeast Xgrip109
      homologue, Spc98, is a spindle-pole body component that interacts with gamma
      tubulin. In vertebrates, Xgrip109 identifies two families of related proteins.
      Xgrip109 and Spc98 have more homology to one family than the other. We show that
      Xgrip109 is a centrosomal protein that directly interacts with gamma tubulin. We
      have developed a complementation assay for centrosome formation using
      demembranated Xenopus sperm and Xenopus egg extract. Using this assay, we show
      that Xgrip109 is necessary for the reassembly of salt-disrupted gammaTuRC and for
      the recruitment of gamma tubulin to the centrosome. Xgrip109, therefore, is
      essential for the formation of a functional centrosome.

PMID- 9566966
TI  - Calpain regulates actin remodeling during cell spreading.
AB  - Previous studies suggest that the Ca2+-dependent proteases, calpains, participate
      in remodeling of the actin cytoskeleton during wound healing and are active
      during cell migration. To directly test the role that calpains play in cell
      spreading, several NIH-3T3- derived clonal cell lines were isolated that
      overexpress the biological inhibitor of calpains, calpastatin. These cells stably
      overexpress calpastatin two- to eightfold relative to controls and differ from
      both parental and control cell lines in morphology, spreading, cytoskeletal
      structure, and biochemical characteristics. Morphologic characteristics of the
      mutant cells include failure to extend lamellipodia, as well as abnormal
      filopodia, extensions, and retractions. Whereas wild-type cells extend lamellae
      within 30 min after plating, all of the calpastatin-overexpressing cell lines
      fail to spread and assemble actin-rich processes. The cells genetically altered
      to overexpress calpastatin display decreased calpain activity as measured in situ
      or in vitro. The ERM protein ezrin, but not radixin or moesin, is markedly
      increased due to calpain inhibition. To confirm that inhibition of calpain
      activity is related to the defect in spreading, pharmacological inhibitors of
      calpain were also analyzed. The cell permeant inhibitors calpeptin and MDL 28,
      170 cause immediate inhibition of spreading. Failure of the intimately related
      processes of filopodia formation and lamellar extension indicate that calpain is
      intimately involved in actin remodeling and cell spreading.

PMID- 9566969
TI  - Characterization of the human homologue of the yeast spc98p and its association
      with gamma-tubulin.
AB  - A trimeric complex formed by Tub4p, the budding yeast gamma-tubulin, and the two
      spindle pole body components, Spc98p and Spc97p, has recently been characterized
      in Saccharomyces cerevisiae. We reasoned that crucial functions, such as the
      control of microtubule nucleation, could be maintained among divergent species.
      SPC98-related sequences were searched in dbEST using the BLASTN program. Primers
      derived from the human expressed sequence tag matching SPC98 were used to clone
      the 5' and 3' cDNA ends by rapid amplification of cDNA ends (RACE)-PCR. The human
      Spc98 cDNA presents an alternative splicing at the 3' end. The deduced protein
      possesses 22% identity and 45% similarity with the yeast homologue. We further
      report that the human Spc98p, like gamma-tubulin, is concentrated at the
      centrosome, although a large fraction is found in cytosolic complexes. Sucrose
      gradient sedimentation of the cytosolic fraction and immunoprecipitation
      experiments demonstrate that both gamma-tubulin and HsSpc98p are in the same
      complex. Interestingly, Xenopus sperm centrosomes, which are incompetent for
      microtubule nucleation before their activation in the egg cytoplasm, were found
      to contain similar amounts of both Spc98p and gamma-tubulin to human somatic
      centrosomes, which are competent for microtubule nucleation. Finally, affinity
      purified antibodies against Spc98p inhibit microtubule nucleation on isolated
      centrosomes, as well as in microinjected cells, suggesting that this novel
      protein is indeed required for the nucleation reaction.

PMID- 9566970
TI  - Anaphase A chromosome movement and poleward spindle microtubule flux occur At
      similar rates in Xenopus extract spindles.
AB  - We have used local fluorescence photoactivation to mark the lattice of spindle
      microtubules during anaphase A in Xenopus extract spindles. We find that both
      poleward spindle microtubule flux and anaphase A chromosome movement occur at
      similar rates ( approximately 2 microm/min). This result suggests that poleward
      microtubule flux, coupled to microtubule depolymerization near the spindle poles,
      is the predominant mechanism for anaphase A in Xenopus egg extracts. In contrast,
      in vertebrate somatic cells a "Pacman" kinetochore mechanism, coupled to
      microtubule depolymerization near the kinetochore, predominates during anaphase
      A. Consistent with the conclusion from fluorescence photoactivation analysis,
      both anaphase A chromosome movement and poleward spindle microtubule flux respond
      similarly to pharmacological perturbations in Xenopus extracts. Furthermore, the
      pharmacological profile of anaphase A in Xenopus extracts differs from the
      previously established profile for anaphase A in vertebrate somatic cells. The
      difference between these profiles is consistent with poleward microtubule flux
      playing the predominant role in anaphase chromosome movement in Xenopus extracts,
      but not in vertebrate somatic cells. We discuss the possible biological
      implications of the existence of two distinct anaphase A mechanisms and their
      differential contributions to poleward chromosome movement in different cell
      types.

PMID- 9566971
TI  - Agrin can mediate acetylcholine receptor gene expression in muscle by aggregation
      of muscle-derived neuregulins.
AB  - The neural isoforms of agrin can stimulate transcription of the acetylcholine
      receptor (AChR) epsilon subunit gene in electrically active muscle fibers, as
      does the motor neuron upon the formation of a neuromuscular junction. It is not
      clear, however, whether this induction involves neuregulins (NRGs), which
      stimulate AChR subunit gene transcription in vitro by activating ErbB receptors.
      In this study, we show that agrin- induced induction of AChR epsilon subunit gene
      transcription is inhibited in cultured myotubes overexpressing an inactive mutant
      of the ErbB2 receptor, demonstrating involvement of the NRG/ErbB pathway in agrin
      induced AChR expression. Furthermore, salt extracts from the surface of cultured
      myotubes induce tyrosine phosphorylation of ErbB2 receptors, indicating that
      muscle cells express biological NRG-like activity on their surface. We further
      demonstrate by RT-PCR analysis that muscle NRGs have Ig-like domains required for
      their immobilization at heparan sulfate proteoglycans (HSPGs) of the
      extracellular matrix. In extrasynaptic regions of innervated muscle fibers in
      vivo, ectopically expressed neural agrin induces the colocalized accumulation of
      AChRs, muscle-derived NRGs, and HSPGs. By using overlay and radioligand-binding
      assays we show that the Ig domain of NRGs bind to the HSPGs agrin and perlecan.
      These findings show that neural agrin can induce AChR subunit gene transcription
      by aggregating muscle HSPGs on the muscle fiber surface that then serve as a
      local sink for focal binding of muscle-derived NRGs to regulate AChR gene
      expression at the neuromuscular junction.

PMID- 9566972
TI  - Absence of the mid-sized neurofilament subunit decreases axonal calibers, levels
      of light neurofilament (NF-L), and neurofilament content.
AB  - Neurofilaments (NFs) are prominent components of large myelinated axons and
      probably the most abundant of neuronal intermediate filament proteins. Here we
      show that mice with a null mutation in the mid-sized NF (NF-M) subunit have
      dramatically decreased levels of light NF (NF-L) and increased levels of heavy NF
      (NF-H). The calibers of both large and small diameter axons in the central and
      peripheral nervous systems are diminished. Axons of mutant animals contain fewer
      neurofilaments and increased numbers of microtubules. Yet the mice lack any overt
      behavioral phenotype or gross structural defects in the nervous system. These
      studies suggest that the NF-M subunit is a major regulator of the level of NF-L
      and that its presence is required to achieve maximal axonal diameter in all size
      classes of myelinated axons.

PMID- 9566973
TI  - Altered cellular responses by varying expression of a ribosomal protein gene:
      sequential coordination of enhancement and suppression of ribosomal protein S3a
      gene expression induces apoptosis.
AB  - A growing body of evidence indicates that individual ribosomal proteins and
      changes in their expression, participate in, and modulate, a variety of cellular
      activities. Our earlier studies have found that apoptosis could be induced by
      inhibiting expression of ribosomal protein S3a (RPS3a) in many tumor cells which
      constitutively express RPS3a at levels much higher than in normal cells. This
      study aimed to investigate cellular responses to enhancement of RPS3a expression,
      and whether apoptosis could be induced by sequential alterations in RPS3a
      expression involving enhancement from an initially low constitutive level,
      followed by suppression. Stably transfected NIH 3T3- derived cell lines were
      established in which exogenous RPS3a expression could be readily manipulated.
      Enhancement of RPS3a expression appeared to induce transformation as assessed by
      well-established criteria such as foci formation and anchorage-independent growth
      in vitro, and formation of tumors in nude mice. These properties were compared
      with those observed in ras-transformed NIH 3T3 cells. Apparent transformation
      occurred only when enhanced RPS3a-expressing cells were in close cell-cell
      contact. Suppression of enhanced RPS3a expression was observed to induce
      apoptosis as assessed by various morphological and biochemical characteristics
      including cell shrinkage, membrane blebbing, chromatin condensation, nuclear and
      cell fragmentation, phosphatidylserine externalization, and internucleosomal DNA
      fragmentation. This induction of apoptosis was not specific to apparently
      transformed cells, as cells at low confluence, which likewise expressed RPS3a at
      enhanced levels but exhibited no morphological transformation, underwent
      apoptosis when RPS3a expression was inhibited. These results support a role for
      RPS3a in the apoptotic process, but not as an oncoprotein per se.

PMID- 9566974
TI  - Vinculin is part of the cadherin-catenin junctional complex: complex formation
      between alpha-catenin and vinculin.
AB  - In epithelial cells, alpha-, beta-, and gamma-catenin are involved in linking the
      peripheral microfilament belt to the transmembrane protein E-cadherin. alpha
      Catenin exhibits sequence homologies over three regions to vinculin, another
      adherens junction protein. While vinculin is found in cell-matrix and cell-cell
      contacts, alpha-catenin is restricted to the latter. To elucidate, whether
      vinculin is part of the cell-cell junctional complex, we investigated complex
      formation and intracellular targeting of vinculin and alpha-catenin. We show that
      alpha-catenin colocalizes at cell-cell contacts with endogenous vinculin and also
      with the transfected vinculin head domain forming immunoprecipitable complexes.
      In vitro, the vinculin NH2-terminal head binds to alpha-catenin, as seen by
      immunoprecipitation, dot overlay, cosedimentation, and surface plasmon resonance
      measurements. The Kd of the complex was determined to 2-4 x 10(-7) M. As seen by
      overlays and affinity mass spectrometry, the COOH-terminal region of alpha
      catenin is involved in this interaction. Complex formation of vinculin and alpha
      catenin was challenged in transfected cells. In PtK2 cells, intact alpha-catenin
      and alpha-catenin1-670, harboring the beta-catenin- binding site, were directed
      to cell-cell contacts. In contrast, alpha-catenin697-906 fragments were recruited
      to cell-cell contacts, focal adhesions, and stress fibers. Our results imply that
      in vivo alpha-catenin, like vinculin, is tightly regulated in its ligand binding
      activity.

PMID- 9566975
TI  - Effects of forced expression of an NH2-terminal truncated beta-Catenin on mouse
      intestinal epithelial homeostasis.
AB  - beta-Catenin functions as a downstream component of the Wnt/Wingless signal
      transduction pathway and as an effector of cell-cell adhesion through its
      association with cadherins. To explore the in vivo effects of beta-catenin on
      proliferation, cell fate specification, adhesion, and migration in a mammalian
      epithelium, a human NH2-terminal truncation mutant (DeltaN89 beta-catenin) was
      expressed in the 129/Sv embryonic stem cell-derived component of the small
      intestine of adult C57Bl/6-ROSA26 left and right arrow 129/Sv chimeric mice.
      DeltaN89 beta-Catenin was chosen because mutants of this type are more stable
      than the wild-type protein, and phenocopy activation of the Wnt/Wingless
      signaling pathway in Xenopus and Drosophila. DeltaN89 beta-Catenin had several
      effects. Cell division was stimulated fourfold in undifferentiated cells located
      in the proliferative compartment of the intestine (crypts of Lieberkuhn). The
      proliferative response was not associated with any discernible changes in cell
      fate specification but was accompanied by a three- to fourfold increase in crypt
      apoptosis. There was a marked augmentation of E-cadherin at the adherens
      junctions and basolateral surfaces of 129/Sv (DeltaN89 beta-catenin) intestinal
      epithelial cells and an accompanying slowing of cellular migration along crypt
      villus units. 1-2% of 129/Sv (DeltaN89 beta-catenin) villi exhibited an abnormal
      branched architecture. Forced expression of DeltaN89 beta-catenin expression did
      not perturb the level or intracellular distribution of the tumor suppressor
      adenomatous polyposis coli (APC). The ability of DeltaN89 beta-catenin to
      interact with normal cellular pools of APC and/or augmented pools of E-cadherin
      may have helped prevent the 129/Sv gut epithelium from undergoing neoplastic
      transformation during the 10-mo period that animals were studied. Together, these
      in vivo studies emphasize the importance of beta-catenin in regulating normal
      adhesive and signaling functions within this epithelium.

PMID- 9566976
TI  - The juxtamembrane region of the cadherin cytoplasmic tail supports lateral
      clustering, adhesive strengthening, and interaction with p120ctn.
AB  - Cadherin cell-cell adhesion molecules form membrane-spanning molecular complexes
      that couple homophilic binding by the cadherin ectodomain to the actin
      cytoskeleton. A fundamental issue in cadherin biology is how this complex
      converts the weak intrinsic binding activity of the ectodomain into strong
      adhesion. Recently we demonstrated that cellular cadherins cluster in a ligand
      dependent fashion when cells attached to substrata coated with the adhesive
      ectodomain of Xenopus C-cadherin (CEC1-5). Moreover, forced clustering of the
      ectodomain alone significantly strengthened adhesiveness (Yap, A.S., W.M.
      Brieher, M. Pruschy, and B.M. Gumbiner. Curr. Biol. 7:308-315). In this study we
      sought to identify the determinants of the cadherin cytoplasmic tail responsible
      for clustering activity. A deletion mutant of C-cadherin (CT669) that retained
      the juxtamembrane 94-amino acid region of the cytoplasmic tail, but not the beta
      catenin-binding domain, clustered upon attachment to substrata coated with CEC1
      5. Like wild-type C-cadherin, this clustering was ligand dependent. In contrast,
      mutant molecules lacking either the complete cytoplasmic tail or just the
      juxtamembrane region did not cluster. The juxtamembrane region was itself
      sufficient to induce clustering when fused to a heterologous membrane-anchored
      protein, albeit in a ligand-independent fashion. The CT669 cadherin mutant also
      displayed significant adhesive activity when tested in laminar flow detachment
      assays and aggregation assays. Purification of proteins binding to the
      juxtamembrane region revealed that the major associated protein is p120(ctn).
      These findings identify the juxtamembrane region of the cadherin cytoplasmic tail
      as a functionally active region supporting cadherin clustering and adhesive
      strength and raise the possibility that p120(ctn) is involved in clustering and
      cell adhesion.

PMID- 9566977
TI  - Regulation of endothelial cell motility by complexes of tetraspan molecules
      CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial
      lateral junctions.
AB  - Cell-to-cell junction structures play a key role in cell growth rate control and
      cell polarization. In endothelial cells (EC), these structures are also involved
      in regulation of vascular permeability and leukocyte extravasation. To identify
      novel components in EC intercellular junctions, mAbs against these cells were
      produced and selected using a morphological screening by immunofluorescence
      microscopy. Two novel mAbs, LIA1/1 and VJ1/16, specifically recognized a 25-kD
      protein that was selectively localized at cell-cell junctions of EC, both in the
      primary formation of cell monolayers and when EC reorganized in the process of
      wound healing. This antigen corresponded to the recently cloned platelet
      endothelial tetraspan antigen CD151/PETA-3 (platelet-endothelial tetraspan
      antigen-3), and was consistently detected at EC cell-cell contact sites. In
      addition to CD151/PETA-3, two other members of the tetraspan superfamily, CD9 and
      CD81/ TAPA-1 (target of antiproliferative antibody-1), localized at endothelial
      cell-to-cell junctions. Biochemical analysis demonstrated molecular associations
      among tetraspan molecules themselves and those of CD151/ PETA-3 and CD9 with
      alpha3 beta1 integrin. Interestingly, mAbs directed to both CD151/PETA-3 and
      CD81/ TAPA-1 as well as mAb specific for alpha3 integrin, were able to inhibit
      the migration of ECs in the process of wound healing. The engagement of
      CD151/PETA-3 and CD81/TAPA-1 inhibited the movement of individual ECs, as
      determined by quantitative time-lapse video microscopy studies. Furthermore, mAbs
      against the CD151/PETA-3 molecule diminished the rate of EC invasion into
      collagen gels. In addition, these mAbs were able to increase the adhesion of EC
      to extracellular matrix proteins. Together these results indicate that CD81/TAPA
      1 and CD151/PETA-3 tetraspan molecules are components of the endothelial lateral
      junctions implicated in the regulation of cell motility, either directly or by
      modulation of the function of the associated integrin heterodimers.

PMID- 9566978
TI  - PDGF, TGF-beta, and heterotypic cell-cell interactions mediate endothelial cell
      induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle
      fate.
AB  - We aimed to determine if and how endothelial cells (EC) recruit precursors of
      smooth muscle cells and pericytes and induce their differentiation during vessel
      formation. Multipotent embryonic 10T1/2 cells were used as presumptive mural cell
      precursors. In an under-agarose coculture, EC induced migration of 10T1/2 cells
      via platelet-derived growth factor BB. 10T1/2 cells in coculture with EC changed
      from polygonal to spindle-shaped, reminiscent of smooth muscle cells in culture.
      Immunohistochemical and Western blot analyses were used to examine the expression
      of smooth muscle (SM)-specific markers in 10T1/2 cells cultured in the absence
      and presence of EC. SM-myosin, SM22alpha, and calponin proteins were undetectable
      in 10T1/2 cells cultured alone; however, expression of all three SM-specific
      proteins was significantly induced in 10T1/2 cells cocultured with EC. Treatment
      of 10T1/2 cells with TGF-beta induced phenotypic changes and changes in SM
      markers similar to those seen in the cocultures. Neutralization of TGF-beta in
      the cocultures blocked expression of the SM markers and the shape change. To
      assess the ability of 10T1/2 cells to contribute to the developing vessel wall in
      vivo, prelabeled 10T1/2 cells were grown in a collagen matrix and implanted
      subcutaneously into mice. The fluorescently marked cells became incorporated into
      the medial layer of developing vessels where they expressed SM markers. These in
      vitro and in vivo observations shed light on the cell-cell interactions that
      occur during vessel development, as well as in pathologies in which developmental
      processes are recapitulated.

PMID- 9566979
TI  - Mannose 6-phosphate/insulin-like growth factor-II receptor targets the urokinase
      receptor to lysosomes via a novel binding interaction.
AB  - The urokinase-type plasminogen activator receptor (uPAR) plays an important role
      on the cell surface in mediating extracellular degradative processes and
      formation of active TGF-beta, and in nonproteolytic events such as cell adhesion,
      migration, and transmembrane signaling. We have searched for mechanisms that
      determine the cellular location of uPAR and may participate in its disposal. When
      using purified receptor preparations, we find that uPAR binds to the cation
      independent, mannose 6-phosphate/insulin-like growth factor-II (IGF-II) receptor
      (CIMPR) with an affinity in the low micromolar range, but not to the 46-kD,
      cation-dependent, mannose 6-phosphate receptor (CDMPR). The binding is not
      perturbed by uPA and appears to involve domains DII + DIII of the uPAR protein
      moiety, but not the glycosylphosphatidylinositol anchor. The binding occurs at
      site(s) on the CIMPR different from those engaged in binding of mannose 6
      phosphate epitopes or IGF-II. To evaluate the significance of the binding,
      immunofluorescence and immunoelectron microscopy studies were performed in
      transfected cells, and the results show that wild-type CIMPR, but not CIMPR
      lacking an intact sorting signal, modulates the subcellular distribution of uPAR
      and is capable of directing it to lysosomes. We conclude that a site within
      CIMPR, distinct from its previously known ligand binding sites, binds uPAR and
      modulates its subcellular distribution.

PMID- 9566980
TI  - Calcium determines the supramolecular organization of fibrillin-rich
      microfibrils.
AB  - Microfibrils are ubiquitous fibrillin-rich polymers that are thought to provide
      long-range elasticity to extracellular matrices, including the zonular filaments
      of mammalian eyes. X-ray diffraction of hydrated bovine zonular filaments
      demonstrated meridional diffraction peaks indexing on a fundamental axial
      periodicity (D) of approximately 56 nm. A Ca2+-induced reversible change in the
      intensities of the meridional Bragg peaks indicated that supramolecular
      rearrangements occurred in response to altered concentrations of free Ca2+. In
      the presence of Ca2+, the dominant diffracting subspecies were microfibrils
      aligned in an axial 0.33-D stagger. The removal of Ca2+ caused an enhanced
      regularity in molecular spacing of individual microfibrils, and the contribution
      from microfibrils not involved in staggered arrays became more dominant. Scanning
      transmission electron microscopy of isolated microfibrils revealed that Ca2+
      removal or addition caused significant, reversible changes in microfibril mass
      distribution and periodicity. These results were consistent with evidence from x
      ray diffraction. Simulated meridional x-ray diffraction profiles and analyses of
      isolated Ca2+-containing, staggered microfibrillar arrays were used to interpret
      the effects of Ca2+. These observations highlight the importance of Ca2+ to
      microfibrils and microfibrillar arrays in vivo.

PMID- 9566981
TI  - Bone matrix proteins: isolation and characterization of a novel cell-binding
      keratan sulfate proteoglycan (osteoadherin) from bovine bone.
AB  - A small cell-binding proteoglycan for which we propose the name osteoadherin was
      extracted from bovine bone with guanidine hydrochloride-containing EDTA. It was
      purified to homogeneity using a combination of ion-exchange chromatography,
      hydroxyapatite chromatography, and gel filtration. The Mof the proteoglycan was
      85, 000 as determined by SDS-PAGE. The protein is rich in aspartic acid, glutamic
      acid, and leucine. Two internal octapeptides from the proteoglycan contained the
      sequences Glu-Ile-Asn-Leu-Ser-His-Asn-Lys and Arg-Asp-Leu-Tyr-Phe-Asn-Lys-Ile.
      These sequences are not previously described, and support the notion that
      osteoadherin belongs to the family of leucine-rich repeat proteins. A
      monospecific antiserum was raised in rabbits. An enzyme-linked immunosorbent
      assay was developed, and showed the osteoadherin content of bone extracts to be
      0.4 mg/g of tissue wet weight, whereas none was found in extracts of various
      other bovine tissues. Metabolic labeling of primary bovine osteoblasts followed
      by immunoprecipitation showed the cells to synthesize and secrete the
      proteoglycan. Digesting the immunoprecipitated osteoadherin with N-glycosidase
      reduced its apparent size to 47 kD, thus showing the presence of several N-linked
      oligosaccharides. Digestion with keratanase indicated some of the
      oligosaccharides to be extended to keratan sulfate chains. In immunohistochemical
      studies of the bovine fetal rib growth plate, osteoadherin was exclusively
      identified in the primary bone spongiosa. Osteoadherin binds to hydroxyapatite. A
      potential function of this proteoglycan is to bind cells, since we showed it to
      be as efficient as fibronectin in promoting osteoblast attachment in vitro. The
      binding appears to be mediated by the integrin alphavbeta3, since this was the
      only integrin isolated by osteoadherin affinity chromatography of surface
      iodinated osteoblast extracts.

PMID- 9566982
TI  - Dietary intake and adequacy of vitamin K.
AB  - The current daily recommended dietary allowance for vitamin K is 1 microg/kg.
      Reliable measurements of vitamin K content in foods are now available, and data
      from 11 studies of vitamin K intake indicate that the mean intake of young adults
      is approximately 80 microg phylloquinone/d and that older adults consume
      approximately 150 microg/d. The vitamin K concentration in most foods is very low
      (<10 microg/100 g), and the majority of the vitamin is obtained from a few leafy
      green vegetables and four vegetable oils (soybean, cottonseed, canola and olive)
      that contain high amounts. Limited data indicate that absorption of phylloquinone
      from a food matrix is poor. Hydrogenated oils also contain appreciable amounts of
      2', 3'-dihydrophylloquinone of unknown physiological importance. Menaquinones
      absorbed from the diet or the gut appear to provide only a minor portion of the
      human daily requirement. Measures of the extent to which plasma prothrombin or
      serum osteocalcin lack essential gamma-carboxyglutamic acid residues formed by
      vitamin K action, or the urinary excretion of this amino acid, provide more
      sensitive measures of vitamin K status than measures of plasma phylloquinone or
      insensitive clotting assays.

PMID- 9566983
TI  - Old and new substrates in clinical nutrition.

PMID- 9566984
TI  - Pharmacological nutrition after burn injury.
AB  - Burn patients develop pathophysiological alterations, which include extensive
      nitrogen loss, malnutrition, markedly increased metabolic rate and immunologic
      deficiency. This predisposes burn patients to frequent infections, poor wound
      healing, increased length of hospitalization and increased mortality. The
      nutritional support requires high protein and high energy diets preferably
      administered enterally soon after injury. The effects of increased dietary
      components such as glutamine, arginine and (n-3) fatty acids and related
      compounds have been evaluated in burn victims. These components, when supplied in
      quantities two to seven times of those in normal diets of healthy persons, appear
      to have beneficial pharmacological effects on the pathophysiological alterations
      associated with burns. However, the efficacy of immune-enhancing diets remains to
      be convincingly shown.

PMID- 9566985
TI  - A diet containing chickpeas and wheat offers less protection against colon tumors
      than a casein and wheat diet in dimethylhydrazine-treated rats.
AB  - We examined the influence of extruded chickpeas and wheat relative to casein and
      wheat in a dimethylhydrazine (DMH)-induced colon tumor study in male Sprague
      Dawley rats. The three diets, based on a modified AIN76 rodent diet with fat
      present at 10 g/100 g dry matter (DM), were as follows: casein with wheat starch
      (Cas/S) as control, casein with wheat (Cas/W) and chickpeas with wheat (CP/W).
      All diets were fed from 5 wk of age throughout the 28-wk study. At 28 wk, there
      was a significantly lower incidence of large intestinal tumors in rats fed Cas/W
      relative to those fed CP/W ( 11 vs. 56%, chi-square test, P = 0.018). The colonic
      tumor burden (tumors/tumor-bearing animal) was not different in Cas/W-fed and
      CP/W-fed rats (1 vs. 1.7), but the tumor mass index was significantly lower in
      the former group (0.22 vs. 1.21, P = 0.026). Rats fed the CP/W diet had
      significantly lower plasma cholesterol concentration (P < 0.01) than rats fed the
      other two diets. The cecal contents of rats fed the CP/W diet had significantly
      greater relative weights (46%, P < 0.05) than those of the Cas/W-fed rats; this
      was associated with higher concentrations of all short-chain fatty acids. Fecal
      analyses showed significantly (P < 0.05) higher concentrations of total fat
      (54%), total steroids (83%) and secondary bile acids (179%) in the CP/W-fed rats
      relative those fed Cas/W. There were higher concentrations of nitrogen in the
      feces of CP/W rats relative to the Cas/W-fed rats (84%, P < 0.05), associated
      with greater fecal weights (67%, P < 0.05). Although wheat and its fibers have
      been shown to be protective against DMH-induced cancers in rats, this was not the
      case in this study in which chickpeas (45 g/100 g diet) provided the protein and
      were an important source of soluble fiber. Elevated fat, secondary bile acid
      concentrations and/or nitrogenous compounds could be responsible for the
      increased colon tumorigenesis seen and may reflect a legume effect.

PMID- 9566986
TI  - Exercise training down-regulates hepatic lipogenic enzymes in meal-fed rats:
      fructose versus complex-carbohydrate diets.
AB  - The maximal activity and mRNA abundance of hepatic fatty acid synthase (FAS) and
      other lipogenic enzymes were investigated in rats meal-fed either a high fructose
      (F) or a high cornstarch (C) diet. The diet contained 50% F or C (g/100 g),
      casein (20%), cornstarch (16.13%), corn oil (5%), minerals (5.37%), vitamins (1%)
      and Solka-floc (2%). Female Sprague-Dawley rats (n = 44) were randomly divided
      into C or F groups that were meal-fed for 3 h/d; each group was subdivided into
      exercise-trained (T) and untrained (U) groups. Treadmill training was performed 4
      h after the initiation of the meal at 25 m/min, 10% grade for 2 h/d, 5 d/wk, for
      10 wk. Rats were killed 9 h after the meal and 27 h after the last training
      session. F-fed rats had significantly higher activities of all lipogenic enzymes
      assayed and mRNA abundance of FAS and acetyl-coenzyme A carboxylase (ACC) than C
      rats (P < 0.05). Concentrations of plasma insulin and glucose and liver pyruvate
      were not altered by F feeding. Proportions of the fatty acids 18:2 and 20:4 were
      lower, whereas those of 16:0 and 16:1 were higher, in livers of F than of C rats
      (P < 0.05). Training decreased FAS activity by 50% (P < 0.05), without affecting
      FAS mRNA level in C rats; this down-regulation was absent in the F rats. ACC mRNA
      abundance tended to be lower in CT than in CU rats (P < 0.075). L-Type pyruvate
      kinase activity was lower in FT than in FU rats (P < 0.05), whereas other
      lipogenic enzyme activities did not differ between T and U rats of each diet
      group. We conclude that hepatic lipogenic enzyme induction by high carbohydrate
      meal feeding may be inhibited by exercise training and that a fructose-rich diet
      may attenuate this training-induced down-regulation.

PMID- 9566987
TI  - Histidase expression is regulated by dietary protein at the pretranslational
      level in rat liver.
AB  - The effect of dietary protein on the expression of histidase (Hal) was
      investigated to understand the mechanism of induction of histidase by a high
      protein diet. In this study, we examined the following: 1) the effect of 0, 6,
      18, 35 and 50% casein diets on hepatic and epidermal Hal activity, amount of the
      enzyme and Hal-mRNA; 2) the effect of a high histidine diet (1.25%) on Hal
      expression; 3) the response of Hal expression in rats fed a 10% casein diet and
      injected with glucagon (0.6 mg /(100 g body wt.d); and 4) the half-lives of the
      enzyme and Hal-mRNA in rats fed an 80% casein diet for 7 d followed by a protein
      free diet. Hal activity increased as the protein content in the diet increased (r
      = 0.986, P < 0.001) and was associated with a significant increase in Vmax
      without a change in Km. The dietary regulation was liver specific because skin
      Hal was unresponsive. Increments in hepatic Hal activity were accompanied by
      concomitant significant increases in the amount of histidase and its mRNA. The
      response was more pronounced in rats fed diets containing >18% casein. Rats fed a
      12% casein diet containing 1.25% histidine did not have different Hal activity
      and mRNA levels compared with rats fed a 12% casein diet, indicating that Hal
      expression is not modified by its substrate. Injection of glucagon into rats fed
      the 10% casein diet increased Hal activity threefold and Hal- mRNA expression
      fivefold compared with uninjected rats fed the same diet. The apparent half-life
      of hepatic histidase in protein-depleted rats previously fed an 80% casein diet
      was 2.8 d, whereas the half-life of Hal-mRNA was 17 h. In summary, these data
      support the hypothesis that Hal expression is regulated by dietary protein at the
      pretranslational level in rat liver, and that glucagon is one of the hormones
      involved in the induction of Hal.

PMID- 9566988
TI  - Metallothionein knockout and transgenic mice exhibit altered intestinal
      processing of zinc with uniform zinc-dependent zinc transporter-1 expression.
AB  - A role for metallothionein in intestinal zinc absorption has been the subject of
      considerable debate. If metallothionein affects zinc absorption, then those
      factors that induce metallothionein synthesis (e.g., heavy metals, hormones)
      should alter zinc absorption and homeostasis. The present studies used
      metallothionein transgenic mice (overexpressing) and metallothionein knockout
      mice (no expression of metallothionein-1 or metallothionein-2) to examine
      directly the effects of metallothionein on zinc absorption, independent of
      secondary effects that could be caused by metallothionein inducers. Zinc
      absorption was examined by administering a single oral zinc dose (0.5 mmol/kg) by
      feeding tube to metallothionein transgenic and metallothionein knockout mice and
      measuring the serum zinc concentration. Two hours after the dose, the serum zinc
      concentration was 2.3 times higher in metallothionein knockout mice than in their
      control strain. Conversely, the concentration was elevated only one third as much
      in the metallothionein transgenic mice as in their controls after the zinc dose.
      We found that the serum zinc concentration was inversely related to the level of
      metallothionein protein. The intestinal zinc content was higher in the
      metallothionein knockout mice, however, suggesting that metallothionein did not
      reduce zinc absorption by simply sequestering zinc in the mucosa. The expression
      of the zinc transporter ZnT-1 was directly related to the serum zinc level and
      was independent of the level of metallothionein. These results further support
      metallothionein as an important component for reducing the efficiency of zinc
      absorption at elevated zinc intakes.

PMID- 9566990
TI  - Intake of soy protein and soy protein extracts influences lipid metabolism and
      hepatic gene expression in gerbils.
AB  - The ability of alcohol extract of isolated soy protein to contribute to the
      hypochoesterolemic effect mediated by the intake of soy protein was tested in
      gerbils. Gerbils were assigned to five different groups (n = 8) and provided
      experimental diets for 28 d. Diets contained either casein or alcohol-washed
      isolated soy protein (ISP). The ISP diet was provided alone, or supplemented with
      one of three different levels of an alcohol extract of isolated soy protein
      contributing either 2.1, 3.6 or 6.2 mg isoflavones/g protein. Gerbils fed all of
      the soy-based diets had significantly lower (P < 0.05) total cholesterol, LDL +
      VLDL cholesterol, and apolipoprotein B concentrations than those fed casein. The
      addition of the alcohol extract to ISP did not reduce serum cholesterol
      concentrations any further, but reduced hepatic apolipoprotein A-I mRNA levels (P
      < 0. 05) compared with casein- and ISP-fed groups. Levels of apolipoprotein E
      mRNA were not affected by diet. These data suggest that in gerbils, consumption
      of an isoflavone-containing extract does not contribute to the
      hypocholesterolemic effect of alcohol-extracted soy, but may influence lipid
      metabolism by altering gene expression for lipid-related genes.

PMID- 9566989
TI  - Ascorbic acid deficiency changes hepatic gene expression of acute phase proteins
      in scurvy-prone ODS rats.
AB  - The ODS rat (genotype od/od), which has a hereditary defect in ascorbic acid
      biosynthesis, was used to investigate the effects of ascorbic acid deficiency on
      the hepatic gene expression of both the positive acute phase proteins,
      haptoglobin and alpha1-acid glycoprotein, and the negative acute phase proteins,
      apolipoprotein A-I and albumin. Male ODS rats (6 wk old, body weight
      approximately 140 g) were fed a basal diet containing ascorbic acid (300 mg/kg
      diet) or a diet without ascorbic acid for 14 d. Ascorbic acid deficiency
      significantly elevated the serum concentration of haptoglobin and significantly
      lowered those of apolipoprotein A-I and albumin. The hepatic mRNA levels of
      haptoglobin and alpha1-acid glycoprotein in the ascorbic acid-deficient rats were
      significantly elevated on d 12, and reached 260 (P < 0.05) and 360% (P < 0.01) of
      respective values in the control rats on d 14. On the contrary, the hepatic mRNA
      levels of apolipoprotein A-I and albumin in the ascorbic acid-deficient rats were
      lowered to 68 (P < 0.01) and 71% (P < 0.05) of respective values in the control
      rats on d 14. Although ascorbic acid deficiency significantly elevated the serum
      corticosterone concentration on d 14, the changes in mRNA levels of haptoglobin,
      alpha1-acid glycoprotein, apolipoprotein A-I and albumin due to ascorbic acid
      deficiency were not affected by adrenalectomy, as assessed in a separate
      experiment. The serum concentration of interleukin-6, an inflammatory cytokine
      that stimulates gene expression of some acute phase proteins, was significantly
      higher in the ascorbic acid-deficient rats on d 14 than in the control rats.
      These results suggest that ascorbic acid deficiency causes physiologic changes
      similar to those that occur in the acute phase response.

PMID- 9566991
TI  - Stimulation of epithelial cell proliferation of isolated distal colon of rats by
      continuous colonic infusion of ammonia or short-chain fatty acids is nonadditive.
AB  - Dietary fibers accelerate colonic epithelial cell proliferation at least in part
      by modulating bacterial metabolism in the large intestine. Ammonia and short
      chain fatty acids (SCFA) are major metabolites of hindgut bacteria and are
      believed to affect epithelial cell kinetics of the colon. However, the effect of
      luminal ammonia itself and the possible interaction of ammonia with SCFA on
      colonic epithelial cell proliferation have not yet been studied. The colon of
      rats was surgically isolated and continuously administered infusates with saline,
      ammonia, SCFA or both into the isolated colon for 7 d in a two-way factorial
      design. On d 7, vincrystine sulfate was administered intravenously to cause
      metaphase arrest. The activity of epithelial cell proliferation in the distal
      colon was estimated by using a stathmokinetic method and by histologic
      examination. The crypt size was significantly larger in rats given infusates
      containing SCFA than in rats given infusates without SCFA. Infusion of ammonia or
      SCFA significantly stimulated colonic epithelial cell proliferation compared with
      the saline infusion. Infusion of both ammonia and SCFA resulted in accumulated
      mitoses per crypt that did not differ from the other three infusions although the
      value tended to be lower than when SCFA alone were infused. Thus, stimulation of
      epithelial cell proliferation by ammonia and SCFA is not additive, and the
      interaction between them should be considered when the effects of dietary fibers
      on gut epithelial proliferation are investigated.

PMID- 9566992
TI  - Hydroxypropyl-modified potato starch increases fecal bile acid excretion in rats.
AB  - The effects of hydroxypropyl potato starches (HPS) of three different degrees of
      substitution (DS) on concentration of plasma cholesterol, apparent digestibility
      of protein, fecal excretion of bile acids, fecal output and cecal pool of organic
      acids such as acetic, propionic, butyric, lactic and succinic acid were studied
      in rats in Experiment 1. In Experiment 2, the effects of hydroxypropyl distarch
      phosphate (HDP) of three different degrees of cross-linking (DC) on the same
      indexes were studied. Gelatinized potato starch that was not modified chemically
      (PS) was used as a control. Rats were fed a fiber-free, purified diet containing
      either HPS, HDP or PS (100 g/kg) for 21 d. In each experiment, fecal output was
      greater and fecal excretion of bile acids was higher in rats fed the HPS diets
      with higher DS and the HDP diets compared with control rats fed the PS diet.
      Apparent protein digestibility in rats fed the HPS diets with higher DS and the
      HDP diets with higher DC was lower than that in control rats fed the PS diet. The
      pool size of cecal organic acids was not affected by diet. In Experiment 1,
      apparent protein digestibility, fecal output and fecal bile acids excretion were
      significantly correlated with DS (r = -0.994, P = 0.0059; r = 0.976, P = 0.0236;
      and r = 0.899, P = 0.0077, respectively). The plasma cholesterol concentration
      was significantly lower in rats fed the HPS diets than in control rats fed the PS
      diet. The HPS diets resulted in higher proportions of propionic acid, lactic acid
      and succinic acid and a lower proportion of n-butyric acid than the PS diet. In
      Experiment 2, apparent protein digestibility was significantly correlated with
      DSP (r = 0.996, P = 0.0028), which was inversely related to DC. The HDP diets did
      not affect the plasma cholesterol concentration. The HDP diets resulted in higher
      proportions of acetic acid, lactic acid and succinic acid and a lower proportion
      of n-butyric acid than the PS diet. These results suggest that the physiological
      effects of chemically modified starches are affected by the type of modification.

PMID- 9566993
TI  - Iron nutritional status is improved in Brazilian preterm infants fed food cooked
      in iron pots.
AB  - To determine the efficacy of cooking food in iron pots to prevent anemia in
      premature infants, a longitudinal study on iron nutritional status was conducted
      in preterm, healthy infants from families of low socioeconomic level between mo 4
      and 12 of life. The infants were divided randomly into two groups. The study
      group consisted of 22 infants whose food was cooked in iron pots; the control
      group consisted of 23 infants whose food was cooked in aluminum pots.
      Supplemental iron [2 mg/(kg.d)] was recommended from 15 d to 12 mo of age for
      both groups. At 12 mo of age, the group fed food cooked in iron pots had
      significantly better hematologic values than the group fed food cooked in
      aluminum pots. Differences included hemoglobin (116 +/- 16 vs. 103 +/- 20 g/L, P
      = 0.02), hematocrit (0.35 +/- 0.04 vs. 0.31 +/- 0.05, P = 0.005), mean
      corpuscular volume (72.1 +/- 10.4 vs. 62.7 +/- 11.1 fL, P = 0.005), free
      erythrocyte protoporphyrin (0.78 +/- 0.60 vs. 1.46 +/- 0.94 mol/L, P = 0.006) and
      serum ferritin (median 5 vs. 0 g/L, P = 0.001). No significant differences
      between groups were observed in serum iron concentration, total iron-binding
      capacity or transferrin saturation. Iron deficiency anemia (hemoglobin </= 110
      g/L) was observed in 36.4% (8 of 22) of infants in the group fed food cooked in
      iron pots and in 73.9% (17 of 23) of the infants fed food cooked in aluminum pots
      (P = 0.03). These results indicate that the iron added to food cooked in iron
      pots is bioavailable. However, this increased iron availability was insufficient
      to satisfy the high iron requirements of this group of preterm infants.

PMID- 9566994
TI  - Fortified foods contribute one half of recommended vitamin A intake in poor urban
      Guatemalan toddlers.
AB  - Vitamin A intake from food sources, not including breast milk, was determined
      from seven consecutive 24-h recalls for 55 children (mean age 20.8 mo, SD 8.9)
      from two poor communities of Guatemala City. Not including vitamin A derived from
      fortified sugar or breast milk, the median daily vitamin A intake was 194 retinol
      equivalents (RE). Including vitamin A derived from fortified sugar but not
      including that derived from breast milk, the median total vitamin A intake (25th
      and 75th percentiles) was 338 RE (146 and 617 RE) of which 78% was preformed
      retinol and 22% provitamin A. More than 90% of total vitamin A intake from non
      breast milk food sources was derived from only 10 items; over half came from
      three fortified foods: fortified sugar, Incaparina and margarine. Sugar samples
      from 91 households in 1991 had a median of 3.3 RE/g (range, 0.0-29.9 RE/g), <25%
      of the target level (13-17 RE/g); nevertheless, fortified sugar provided 25% of
      these children's total vitamin A intake (81 RE/d) from non-breast milk food
      sources and their intake approached the level recommended by the FAO/WHO (400
      RE/d). These results show that fortified foods make an important contribution
      towards vitamin A intake in this sample of poor urban Guatemalan toddlers.

PMID- 9566995
TI  - Full-fat rice bran and oat bran similarly reduce hypercholesterolemia in humans.
AB  - Scientific studies support recommendations to increase dietary soluble fiber as
      part of hyperlipidemia treatment. Rice bran contains minimal soluble fiber, but
      rice bran oil has a hypolipidemic effect. Full-fat rice bran was compared with
      oat bran and a rice starch placebo in hyperlipidemic humans to see if it might
      have a role in the treatment of hyperlipidemia. Moderately hypercholesterolemic
      (5.95-8.02 mmol/L), nonsmoking, nonobese adults were studied in a 6-wk,
      randomized, double-blind, noncross-over trial. Three groups added 84 g/d of a
      heat-stabilized, full-fat, medium-grain rice bran product (n = 14), oat bran
      product (n = 13) or rice starch placebo (n = 17) to their usual low-fat diet.
      Serum cholesterol, triglycerides, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL
      C), apoA1 and apoB were measured before and at the end of the supplementation
      period. Serum cholesterol decreased significantly (P </= 0.05) by 8.3 +/- 2.4%
      and 13.0 +/- 1.8% in the rice bran and oat bran groups, respectively, but there
      was no change in the rice starch group. This change was attributable to LDL-C,
      which decreased by 13.7 +/- 2.8% in the rice bran group and 17.1 +/- 2.4% in the
      oat bran group (P </= 0.05). Serum apoB decreased proportionately. There was no
      consistent effect on triglycerides within each group and HDL-C and apoA
      concentrations did not change. The LDL-C:HDL-C ratio decreased significantly in
      the rice bran and oat bran groups. Stabilized, full-fat rice bran or oat bran,
      added to the prudent diet of hyperlipidemic adults, similarly reduced cholesterol
      and LDL-C and improved lipid ratios in 78% of these individuals. Rice bran, as
      well as oat bran, should be included in the prudent diet of individuals with
      hyperlipidemia.

PMID- 9566996
TI  - Dietary effects on coagulation factor VII vary across genotypes of the R/Q353
      polymorphism in elderly people.
AB  - The objective of this study was to evaluate the association of factor VII with
      dietary factors while also considering the R/Q353 polymorphism. Nutrition is an
      important determinant of coagulation factor VII, which is also genetically
      determined by the R/Q353 polymorphism. High levels of coagulation factor VII
      clotting activity (FVII:C) are associated with the risk of myocardial infarction;
      nutrition may have an effect on these levels if people are genetically
      susceptible to dietary changes. FVII:C was measured in 3005 elderly subjects, and
      the extreme quintiles of the FVII:C distribution were selected for measurement of
      the R/Q353 genotype and FVII:Chr (reflects total factor VII). In these 1158
      subjects, habitual diet was assessed with a semiquantitative food-frequency
      questionnaire. The frequency of the Q353 allele was 0.24 in the lowest and 0.09
      in the highest quintile. The quintiles were combined for linear regression
      analyses. FVII:C was inversely associated with fiber [beta = -0.64 %pooled plasma
      (PP)/g, confidence interval (CI): -1.07,-0.21] and protein intake (beta = -0.16
      %PP/g, CI: -0.31,-0. 01) and positively with saturated fat intake (beta = 0.19
      %PP/g, CI: -0.10,0.48). FVII:Chr was inversely associated with fiber (beta = -0.
      38 %PP/g, CI: -0.71,-0.05). No other associations with diet were observed. The
      inverse association of FVII:C with fiber was stronger in subjects with the RR
      genotype (beta = -0.76 %PP/g, CI: -1.23,-0. 29), than in those with the RQ/QQ
      genotypes (beta = -0.19 %PP/g, CI: -0.97,0.59). The same was found for FVII:Chr.
      The association of FVII:C with saturated fat was positive in those with the RR
      allele and inverse in those carrying the Q allele. These findings suggest that
      the strength of the association between coagulation factor VII and diet varies
      across the genotypes of the R/Q353 polymorphism.

PMID- 9566997
TI  - Poor digestibility of fully hydrogenated soybean oil in rats: a potential benefit
      of hydrogenated fats and oils.
AB  - The digestibility and absorption of dietary triacylglycerols are dependent on a
      number of factors including their fatty acid profile. Data demonstrating poor
      bioavailability of dietary stearic acid would suggest that hydrogenated oil
      sources would have lower digestibility coefficients compared with their native
      oils. To test this hypothesis, postweanling rats were fed one of four diets,
      formulated to contain 40% of energy as fat (assuming complete bioavailability),
      for 14 d. The diets only differed by fat type, containing soybean oil (SBO),
      fully hydrogenated soybean oil (HSB), medium-chain triglyceride oil (MCT), or
      hydrogenated coconut oil (HCO). Rats fed HSB consumed more food during the last 6
      d (155.2 +/- 2.7 g) than those in each of the other groups (MCT: 118.9 +/- 2. 2
      g; HCO: 124.7 +/- 3.2 g; SBO: 123.8 +/- 2.3 g), yet, they did not gain more
      weight. Two-day fecal excretion was almost three times greater in HSB-fed rats
      than in rats fed any other diet (P < 0.0001) because HSB was very poorly
      available. The digestibility coefficients (a measure of bioavailability) of the
      four fats were: HSB (30.9 +/- 1.3%) < HCO (94.5 +/- 0.4%) < SBO (97.0 +/- 0.4%) <
      MCT (98.7 +/- 0.2%) (P < 0.0007). All rats compensated for the incomplete
      availability of the fats, as apparent absorbable energy consumed did not differ
      among diet groups. The present data suggest that HSB only contributes 11.6 kJ/g
      (most fats contribute approximately 37.7 kJ/g) and that not only manufactured fat
      substitutes, such as olestra, but also more conventional fats are incompletely
      available to the body. Foods that currently contain HSB may contribute much less
      utilizable fat and energy than presently realized.

PMID- 9566998
TI  - Dietary fatty acid sources affect conjugated linoleic acid concentrations in milk
      from lactating dairy cows.
AB  - Conjugated linoleic acid (CLA), a naturally occurring anticarcinogen found in
      dairy products, is an intermediary product of ruminal biohydrogenation of
      polyunsaturated fatty acids. Our objective was to determine the effect of
      different dietary oils, which vary in fatty acid composition, on CLA
      concentrations in milk from lactating dairy cows. Twelve Holstein cows were
      randomly assigned to a 3 x 3 Latin square design. Dietary treatments were the
      addition (53 g/kg dietary dry matter) of peanut oil (high oleic acid), sunflower
      oil (high linoleic acid) and linseed oil (high linolenic acid). Each treatment
      period was 2 wk, and milk samples were collected on the last 4 d of each period.
      Milk yield (34.2 +/- 1.3 kg/d) and milk fat (2.25 +/- 0.06%) were not different
      among treatments. Milk protein during the sunflower oil treatment (mean, 3.44%
      protein) was significantly higher (P < 0.01) than during the other treatments.
      Milk fat concentration of CLA during the sunflower oil treatment was
      significantly different from other treatments (P < 0.001) and approximately 500%
      greater than typically observed when cows consume traditional diets. CLA
      concentrations (mg/g of milk fat) were 13.3, 24.4 and 16.7 during peanut oil,
      sunflower oil and linseed oil treatment, respectively. CLA concentration in milk
      fat can be enhanced by the addition of polyunsaturated fatty acids to the diet,
      especially oils high in linoleic acid.

PMID- 9566999
TI  - Carnitine palmitoyltransferase I (CPT I) activity and its regulation by malonyl
      CoA are modulated by age and cold exposure in skeletal muscle mitochondria from
      newborn pigs.
AB  - Whole-body lipid utilization is progressively enhanced during the first postnatal
      day in pigs, especially during cold exposure and muscular shivering
      thermogenesis. This study was designed to examine early postnatal changes in
      fatty acid oxidation potential, carnitine palmitoyltransferase I activity and
      regulation by malonyl-CoA in skeletal muscle mitochondria isolated from newborn
      and 5-d-old piglets. At 5 d of life, pigs were maintained for a 4-h period in
      thermoneutral (30 degreesC) or cold (20 degreesC) conditions. Intermyofibrillar
      and subsarcolemmal mitochondria were isolated from longissimus dorsi and
      rhomboideus muscles. In subsarcolemmal mitochondria, carnitine
      palmitoyltransferase I activity increased with age (P < 0.01) and was 80% lower
      (P < 0.001) than in intermyofibrillar mitochondria. Intermyofibrillar
      mitochondria had high enzyme activities and fatty acid oxidation potential from
      birth. The fatty acids 16:0, 18:1(n-9) and 18:2(n-6) were oxidized at a higher
      rate than 18:0 (-37%) and 8:0 (-55%). Sensitivity of carnitine
      palmitoyltransferase I to malonyl-CoA inhibition and malonyl-CoA levels decreased
      by 47% (P < 0.05) and 33% (P < 0.01) with age, respectively. After 4 h of cold
      exposure, sensitivity of carnitine palmitoyltransferase I to malonyl-CoA was
      unaffected in the rhomboideus and tended to be greater (P < 0.06) in longissimus
      dorsi muscle. Malonyl-CoA levels were lower (P < 0.05) in the rhomboideus and
      were unaffected in longissimus dorsi muscle. These results demonstrate that fatty
      acid oxidation is effective from birth in isolated intermyofibrillar
      mitochondria. The postnatal enhancement of fatty acid utilization observed in
      vivo can be explained, at least in part, by a rise in carnitine
      palmitoyltransferase I activity in subsarcolemmal mitochondria and a modulation
      of its activity by malonyl-CoA in intermyofibrillar mitochondria.

PMID- 9567000
TI  - Maternal dietary protein deficiency decreases amino acid concentrations in fetal
      plasma and allantoic fluid of pigs.
AB  - This study was conducted to test the hypothesis that maternal dietary protein
      deficiency decreases amino acid availability to the fetus, thereby contributing
      to retarded fetal growth. Primiparous gilts selected genetically for low or high
      plasma total cholesterol concentrations (low line and high line, respectively)
      were mated, and then fed 1.8 kg/d of isocaloric diets containing 13% or 0.5%
      crude protein. At d 40 or 60 of gestation, they were hysterectomized, and
      maternal and fetal blood samples as well as amniotic and allantoic fluids were
      obtained for analyses of amino acids, ammonia and urea. Dietary protein
      restriction decreased (P < 0.05) the following: 1) maternal plasma concentrations
      of urea at d 40 and 60 of gestation; 2) fetal plasma concentrations of alanine,
      arginine, branched-chain amino acids (BCAA), glutamine, glycine, lysine,
      ornithine, proline, taurine, threonine and urea at d 60 of gestation; 3) amniotic
      and allantoic fluid concentrations of urea at d 40 and 60 of gestation; and 4)
      allantoic fluid concentrations of alanine, arginine, BCAA, citrulline, cystine,
      glycine, histidine, methionine, proline, serine, taurine, threonine and tyrosine
      at d 40 of gestation, in gilts of both genetic lines. At d 60 of gestation,
      protein deficiency decreased (P < 0.05) allantoic fluid concentrations of
      arginine, cystine, glycine, taurine and tyrosine in low line gilts and of
      cystine, glutamine, ornithine, serine, taurine and tyrosine in high line gilts.
      Low line and high line gilts also differed remarkably in allantoic fluid
      concentrations of arginine, glutamine, ornithine and ammonia at d 40 and 60 of
      gestation. Our results suggest the following: 1) protein-deficient gilts maintain
      maternal plasma concentrations of amino acids by mobilizing maternal protein
      stores and decreasing oxidation of amino acids during the first half of
      gestation; 2) protein deficiency may impair placental transport of amino acids
      from the maternal to the fetal blood; and 3) low line and high line gilts differ
      in fetal amino acid metabolism. Decreases in concentrations of the essential and
      nonessential amino acids in the fetus may be a mechanism whereby maternal dietary
      protein restriction results in fetal growth retardation.

PMID- 9567001
TI  - Increased dermal carotenoid levels assessed by noninvasive reflection
      spectrophotometry correlate with serum levels in women ingesting Betatene.
AB  - beta-Carotene is being used as an oral sun protectant, and evidence indicates
      that carotenoids may protect human skin from light-induced lesions. However,
      limited information is available on the distribution and accumulation of beta
      carotene in skin, especially with respect to various skin regions. With the use
      of reflection spectroscopy, we investigated the accumulation of total carotenoids
      in human skin after repeated supplementation of 12 women with beta-carotene from
      a natural source Betatene, an algal extract. After daily ingestion of 24 mg beta
      carotene (in Betatene) for 12 wk, an increase in carotenoid skin levels was
      observed. Highest basal values were measured in skin of the forehead, palm of the
      hand and dorsal skin, with lower levels measured in skin of the arm and back of
      the hand. Upon treatment, increases in carotenoid skin levels were found in all
      areas as follows: 2.4-fold in forehead, 0.7-fold in dorsal skin, 2.2-fold in the
      palm of the hand, 17-fold on the back of the hand and 1.7-fold on the inside of
      the arm. After cessation of treatment, the carotenoid levels decreased in all
      skin areas. Serum beta-carotene levels were elevated upon treatment and
      correlated with carotenoid skin levels. Correlations for serum vs. skin from the
      palm of the hand (r = 0.94) and skin from the forehead (r = 0.89) were
      calculated, indicating that serum levels appeared to be a suitable indicator for
      carotenoid accumulation in specific regions of the skin. With doses of
      approximately 20-25 mg carotenoids/d, it is possible to raise dermal carotenoid
      levels.

PMID- 9567002
TI  - Chitin but not chitosan supplementation enhances growth of grass shrimp, Penaeus
      monodon.
AB  - The effect of chitin, poly-beta-(1 --> 4)-N-acetyl-glucosamine, and chitosan, a
      polymer of glucosamine obtained by the deacetylation of chitin, on growth and
      nutrient digestibility was studied in grass shrimp, Penaeus monodon. Shrimp were
      fed for 8 wk diets containing no supplement (control) or 2, 5 or 10 g/100 g
      chitin or chitosan. Each diet was fed to triplicate groups of shrimp with a mean
      initial body weight of 0.45 +/- 0.05 g. Significantly higher body weight gains
      were observed in shrimp fed the 5% chitin diet than in those fed the 10% chitin
      or the control diet. The weight gain of shrimp decreased as dietary chitosan
      supplementation level increased (r = 0. 87, P < 0.05). Feed efficiencies (FE) and
      protein efficiency ratios (PER) followed the same pattern. Lower protein and
      lipid digestibilities and lower body protein and lipid contents were observed in
      shrimp fed all chitosan-containing diets than in controls (P < 0.05).
      Carbohydrate digestibility was lower in shrimp fed the 10% chitosan diet than in
      those fed the control diet. Lower protein and lipid digestibilities, body lipid
      content and blood cholesterol concentration were observed in shrimp fed the 10%
      chitin diet compared with controls (P < 0.05). Higher weight gains, body lipid
      contents and blood cholesterol concentrations were observed in shrimp fed the 2
      and 5% chitin diets than in those fed the chitosan diets. Shrimp fed the 5%
      chitin diet had higher protein and lipid digestibilities and higher body protein
      content than those fed the 5% chitosan diet (P < 0.05). These data suggest that
      dietary chitin, supplemented at 5%, enhances P. monodon growth, whereas chitosan
      depresses shrimp growth, regardless of the supplementation level.

PMID- 9567003
TI  - Bioavailability of beta-carotene is lower in raw than in processed carrots and
      spinach in women.
AB  - Populations at risk of vitamin A deficiency usually rely on dietary provitamin A
      carotenoids to meet vitamin A needs, yet bioavailability of these compounds is
      influenced by several factors as follows: location in the plant source, the
      presence of other influencing dietary components, and type and extent of
      processing. The purpose of this study was to examine the plasma beta-carotene
      response to raw vs. processed carrots and spinach. Subjects were eight healthy
      females aged 23-36 y who consumed approximately 9.3 mg beta-carotene daily from
      either raw or thermally processed and pureed vegetables in two 4-wk treatment
      periods in a crossover study. Plasma concentrations of total, all-trans-, and cis
      beta-carotene and alpha-carotene were measured at base line and the end of each
      treatment period by using HPLC assays. Total and all-trans (but not cis) plasma
      beta-carotene concentrations were significantly greater than base-line
      concentrations in the processed feeding period (P < 0. 04) and tended to be
      greater in the raw feeding period (P = 0.08). Daily consumption of processed
      carrots and spinach over a 4-wk period produced an increase in plasma beta
      carotene concentration that averaged three times that associated with consumption
      of the same amount of beta-carotene from these vegetables in the raw form (P =
      0.09). Increased cis isomers provided in the processed vegetables did not result
      in significantly greater plasma cis-beta-carotene isomer concentrations. These
      results suggest that isomerization of beta-carotene by heat treatment does not
      negate the enhanced beta-carotene uptake associated with consuming commercially
      processed vegetables compared with raw vegetables.

PMID- 9567004
TI  - Calcium absorption--a paradigm for mineral absorption.
AB  - Intestinal calcium absorption proceeds by two mechanisms, an active transcellular
      process that takes place in the duodenum and a passive paracellular process
      throughout the small intestine. This article characterizes the three steps of
      transcellular calcium movement-entry, intracellular diffusion and extrusion-and
      identifies conditions that must be satisfied for other mineral ions to move
      transcellularly as part of a transepithelial transport process. Passive calcium
      movement is down a chemical gradient with the amount absorbed by this pathway
      determined in large measure by the sojourn time, most of which is spent in the
      ileum. Because transcellular movement of most mineral ions other than calcium,
      where measured, is either small or negligible, passive transport is likely to be
      the major route of intestinal absorption, the nature of which, however, has not
      been well established experimentally.

PMID- 9567005
TI  - Therapeutic angiogenesis.
AB  - Therapeutic angiogenesis constitutes a fundamental survival mechanism that acts
      to preserve the integrity of tissues subjected to ischemia. Supplemental
      administration of angiogenic cytokines--as recombinant protein or plasmid DNA-
      have been shown to augment collateral development when endogenous angiogenesis is
      suboptimal for organ function, and thus constitute a novel therapeutic option for
      the treatment of cardiovascular disease. These angiogenic cytokines, all of which
      share in common the ability to act as mitogens for endothelial cells, do not
      promote angiogenesis in an indiscriminate fashion; thus angiogenic cytokines
      selectively produce neovascularization in the ischemic tissues. The purpose of
      this review is to consider the mechanisms responsible for therapeutic
      angiogenesis which develops endogenously as well as strategies which have been
      devised to augment this response. The development of blood vessels is considered
      from the context of the embryonic paradigm; certain principles which have emerged
      from studies of pathologic neovascularization; and, principally, the development
      of collateral blood vessels supplying ischemic tissues, either endogenously or in
      response to administered growth factors.

PMID- 9567006
TI  - Pearls in the management of macular disorders. Introduction.

PMID- 9567007
TI  - Diagnostic pearls in the management of vitreomacular disorders.
AB  - The posterior precortical vitreous pocket is a premacular liquefied lacuna that
      is physiologically present in adult eyes. The posterior wall of the pocket
      consists of a thin layer of the vitreous, and its anterior border is delineated
      by vitreous gel. This peculiar structure of the premacular vitreous cortex plays
      a key role in the development of various vitreomacular disorders. In diabetic
      retinopathy, fibrovascular tissue tends to develop along the outer margin of the
      pocket, resulting in a ring- or c-shaped structure. Tangential contraction of the
      posterior wall of the pocket or premacular cortex causes the formation of macular
      holes. The posterior wall of the pocket serves as a major structural component of
      idiopathic premacular fibrosis. The concept of the posterior precortical vitreous
      pocket provides a guideline to manage vitreoretinal disorders occurring in the
      macular area.

PMID- 9567008
TI  - Pearls in the management of macular holes.
AB  - We studied the efficacy of removing the retinal pigment epithelium (RPE) from the
      base of the macular hole to treat 124 eyes of 118 patients with stage 2 (n = 38),
      stage 3 (n = 52), or stage 4 (n = 34) macular hole. The patients ranged in age
      from 42 to 81 years (mean = 66.7 years), and the duration of symptoms
      preoperatively ranged from 1 to 140 months (average = 16.8 months). During
      vitrectomy for the macular hole, the RPE at the base of the hole was gently
      aspirated with either a silicone-tipped extrusion needle or a blunt-tipped 27
      gauge needle. The follow-up period averaged 18.6 months (range = 3 to 48 months).
      The holes resolved in 112 (90%) of the 124 eyes after one surgical procedure. In
      107 eyes with a follow-up period of 6 months or longer, 91 (85.0%) showed
      improved visual acuity of at least 2 lines of Snellen equivalent. The final
      visual acuity was 20/25 or better in 34 (31.8%) and 20/40 or better in 80 (74.8%)
      of the 107 eyes. A complication peculiar to RPE removal is the hypertrophy of the
      RPE. This complication was observed in 15 (14.0%) of the 107 eyes that were
      followed for 6 months or longer. From these results, I conclude that RPE removal
      will improve the anatomical and the visual results in selected macular hole
      cases.

PMID- 9567009
TI  - Surgical management of macular edema.
AB  - Macular edema, often a component of diabetic retinopathy, can be complicated by
      many other diseases. It is considered to be multifactorial and difficult to
      treat. The relation of the vitreous and macular edema is discussed. We examined
      many eyes of patients with diabetic macular edema that improved after spontaneous
      posterior vitreous detachment or vitrectomy for proliferative diabetic
      retinopathy. Recent advances in vitreous surgery have enabled us to treat
      surgically eyes with good visual acuity. We began surgical treatment for macular
      edema without the fibrous membrane in 1990. Here we discuss our experience in
      surgical treatment of macular edema as contrasted to photocoagulation therapy.
      This review is based on the published and unpublished results of our cases of
      more than 100 eyes that underwent vitrectomy for diabetic macular edema.

PMID- 9567010
TI  - Treatment options In subfoveal choroidal neovascularization secondary to age
      related macular degeneration.
AB  - Laser photocoagulation of the entire area of the neovascular lesion is the only
      proven treatment for subfoveal choroidal neovascularization secondary to age
      related macular degeneration with a poor natural history. However, there are some
      limiting factors such as patient eligibility, a significant decline in visual
      acuity after treatment, and a very low possibility of a final vision of 20/100 or
      better. Although no large benefit of other treatment modalities, such as
      indocyanine green videoangiography-guided laser photocoagulation, surgical
      removal of neovascular membranes, and radiation therapy, has yet been proven,
      carefully selected patients may be suitable candidates for such treatments. This
      article reviews the status of treatment modalities for subfoveal choroidal
      neovascularization secondary to age-related macular degeneration, including laser
      photocoagulation of the entire area of the neovascular lesion, and discusses
      factors prognostic of visual outcome in these treatment options.

PMID- 9567011
TI  - Pearls in the management of submacular hematoma.
AB  - Subretinal hemorrhage (SRH), complicated by choroidal neovascularization such as
      age-related macular degeneration, often reduces central vision in middle-aged
      patients. Although the visual results of SRH removal by surgery seem to have
      improved recently, the efficacy has not yet been confirmed in a prospective,
      controlled fashion. Therefore, it cannot be stated with certainty that surgery
      for SRH is more beneficial than the natural course of the disease. However, we
      believe surgery is beneficial in selected patients. Herein, we describe our
      technique for the surgical removal of SRH. The development of safer, more
      effective techniques should further improve patient outcomes.

PMID- 9567012
TI  - Foveal translocation: a comparison of two techniques.
AB  - Subfoveal choroidal neovascular membrane is a leading cause of legal blindness.
      Photocoagulation has been effective, but photocoagulation of the fovea causes a
      decrease in vision immediately after treatment. Surgical removal of the choroidal
      neovascular membrane is effective for choroidal neovascular membrane in some
      cases, but it restores useful vision for reading (20/40 or better) in a small
      number of cases of choroidal neovascular membrane not due to presumed ocular
      histoplasmosis syndrome. A new treatment for subfoveal choroidal neovascular
      membrane, foveal translocation, is an innovative procedure in which the fovea is
      translocated onto healthier retinal pigment epithelium. Three techniques have
      been developed to relocate the retina, 2 of which (retinotomy and scleral
      shortening) we performed in 5 cases each. Preliminary results in these 10 cases
      indicate that foveal translocation provides improvement of visual acuity in 40%
      of eyes and final visual acuities useful for reading (better than 20/40) in 20%
      of eyes undergoing translocation with either technique. Further study is
      essential to refine the amount of translocation needed and to decrease
      complications of the 2 techniques, including retinal detachment, proliferative
      vitreoretinopathy, macular pucker, corneal astigmatism, and constricted visual
      field.

PMID- 9567013
TI  - What role do epidemiology and public health have in dealing with blindness in
      India?

PMID- 9567014
TI  - Ophthalmic antiviral chemotherapy: an overview.
AB  - Antiviral drug development has been slow due to many factors. One such factor is
      the difficulty to block the viral replication in the cell without adversely
      affecting the host cell metabolic activity. Most of the antiviral compounds are
      analogs of purines and pyramidines. Currently available antiviral drugs mainly
      inhibit viral nucleic acid synthesis, hence act only on actively replicating
      viruses. This article presents an overview of some of the commonly used antiviral
      agents in clinical ophthalmology.

PMID- 9567015
TI  - Evaluation of the role of syringing prior to cataract surgery.
AB  - Patients for cataract surgery in India routinely undergo preoperative syringing
      to rule out chronic dacryocystitis. We determined the sensitivity and specificity
      of the clinical test of regurgitation on pressure over the lacrimal sac (ROPLAS)
      as a screening test for chronic dacryocystitis and compared it to syringing. 621
      consecutive outpatients who needed syringing for various reasons (including 318
      who had routine syringing prior to cataract surgery) were examined in a masked
      manner for regurgitation on pressure over the lacrimal sac. They then underwent
      syringing by a trained (masked) observer. The sensitivity and specificity of
      ROPLAS were 93.2% and 99.3%, respectively. Using a 6.6% prevalence of chronic
      dacryocystitis (the prevalence in our cataract population), the negative
      predictive value of the test was 99.5%. In the presence of regurgitation of
      pressure over the sac, the high specificity of ROPLAS confirms chronic
      dacryocystitis. In view of the opportunity costs, when ROPLAS is negative,
      preoperative syringing in cataract is perhaps unnecessary, unless the findings
      are equivocal or the index of suspicion for chronic dacryocystitis is very high.

PMID- 9567016
TI  - Visual outcome and complications of residents learning phacoemulsification.
AB  - The increasing popularity of phacoemulsification in our country raises important
      training issues. We prospectively analyzed the incidence of complications and
      visual outcomes in the initial 70 phacoemulsifications (70 patients) performed by
      the first two residents learning phacoemulsification in our training programme.
      Both were experienced in standard (manual) extracapsular cataract extraction.
      Postoperative follow up of 6 weeks or longer was available in 59 eyes. The 11
      patients (11 eyes) lost to follow up did not have any intra-operative
      complications. The overall incidence of vitreous loss was 10%, similar to the
      frequency of this complication (determined retrospectively) in the first 70
      standard extracapsular cataract extractions performed by the same residents.
      Intraocular lenses (IOL) were successfully implanted in 62 eyes, as planned. One
      IOL dislocated into the vitreous was successfully repositioned. Other
      complications encountered included superior corneal edema (3 eyes), iris damage
      inferiorly (7 eyes) and clinical cystoid macular edema (5 eyes). A best corrected
      visual acuity of 6/12 or better was obtained in 56 (94.8%) of the 59 eyes
      available for the six week follow up. In the eyes with vitreous loss, 6 out of 7
      had visual acuity better than 6/12. No nuclei were lost into the vitreous. The
      rate of surgical complications for residents learning phacoemulsification in a
      supervised manner can be acceptably low.

PMID- 9567017
TI  - Topical aspirin provides protection against galactosemic cataract.
AB  - Effect of twice daily administration of aspirin eyedrops on the onset and
      progression of cataract induced by 30% galactose diet was studied. On the 30th
      day of galactose feeding while all control group rats showed complete stage IV
      opacity, those receiving aspirin eyedrops showed only mild cataractous changes of
      stage I. In vitro studies showed that addition of aspirin to the medium
      significantly decreased dulcitol formation (p < 0.01) and maintained glutathione
      levels (p < 0.02). Intraocular penetration studies using isolated goat cornea
      showed excellent penetration by salicylate indicating feasibility of topical
      administration. The results of the present study demonstrate that topical aspirin
      possesses significant anticataract activity in galactosemic cataract.

PMID- 9567018
TI  - Possible role of lens collagen in cataractogenesis.
AB  - The solubility characteristics of collagen in human cataractous eye lenses were
      studied in relation to age. Post-operative cataractous lenses were collected form
      eye camps in Phulbani district of Orissa. These were preserved in 70% alcohol and
      immediately transferred to the laboratory. Various fractions in the collagen
      obtained from lens capsule of each lens sample were estimated. The salt-soluble
      and the acid-soluble collagens showed positive correlation with age. The
      insoluble and total capsular collagen increased with increasing age. The
      solubility percentage of collagen in salt and acid solutions decreased
      significantly with increasing age. The possible role of lens collagen in the
      development of cataract with increasing age is discussed in the background of
      cross-link theory of aging.

PMID- 9567019
TI  - Blepharitis and lid ulcer as initial ocular manifestation in acquired
      immunodeficiency syndrome patients.

PMID- 9567020
TI  - Lid abscess with extensive molluscum contagiosum in a patient with acquired
      immunodeficiency syndrome.

PMID- 9567021
TI  - Optic neuritis following snake bite.

PMID- 9567022
TI  - Rheumatoid corneal melting.

PMID- 9567023
TI  - Physical and mechanical principles of phacoemulsification and their clinical
      relevance.
AB  - A clear understanding of the physical and mechanical principles that govern
      phacoemulsification can facilitate usage of this technique for effective and
      efficient cataract removal in a variety of clinical situations. This article
      addresses separately, concepts pertaining to the three essential components of
      phacoemulsification, namely, irrigation, aspiration and emulsification. Machine
      settings are suggested for the various techniques presently in use. Finally,
      alternative approaches for lens removal that are currently being investigated are
      briefly discussed.

PMID- 9567024
TI  - Design of a population-based study of visual impairment in India: The Andhra
      Pradesh Eye Disease Study.
AB  - Reliable population-based epidemiologic data regarding vision and ocular
      morbidity, as well as those about the perceptions of people regarding visual
      impairment and eye care, are lacking for the most part in the developing world
      including India. These data are the basis on which effective eye care services
      can be developed. To meet this need we designed the Andhra Pradesh Eye Disease
      Study, a population-based epidemiology study of 10,000 people in the Indian state
      of Andhra Pradesh. The design of this study is described in this paper. Various
      options for the sample size, study areas, sampling procedure, and recruitment of
      subjects were considered. A sample size of 10,000 people, 5,000 each in the < or
      = 30 and > 30 years age groups, was determined to obtain reasonable confidence in
      estimating the prevalence of diseases and odds ratios for risk factors of
      interest. A multistage sampling strategy was chosen for the study which was
      assumed to give a design effect of 1.5 for the estimates. One urban area,
      Hyderabad, and three rural areas, West Godavari, Adilabad and Mahbubnagar
      districts, were selected in Andhra Pradesh. Interview instruments were developed
      to obtain detailed information about demographic data, diet, ocular and systemic
      history, risk factors for eye diseases, visual function, quality of life,
      barriers to eye care, and knowledge about eye diseases. A detailed examination
      procedure was devised to obtain a broad range of normative and abnormal data
      related to eyes and vision. A protocol was developed for doing automated visual
      fields, slitlamp and fundus photography. Computer databases were made in FoxPro
      for data entry and subsequent analysis with SPSS. Pilot studies were done to test
      the instruments, procedures, and logistics of the study in urban and rural areas.
      Information from the Andhra Pradesh Eye Disease Study is expected to help in
      planning and implementation of effective long-term preventive, curative, and
      rehabilitative eye care services in Andhra Pradesh.

PMID- 9567025
TI  - Estimating cataract blindness in India.

PMID- 9567026
TI  - Treatment outcome in diabetic macular edema.

PMID- 9567027
TI  - Treatment outcome in diabetic macular edema.

PMID- 9567028
TI  - Central retinal vein occlusion study.

PMID- 9567029
TI  - [Determination of energy window width and position for the triple energy window
      (TEW) scatter compensation method].
AB  - Since primary photons can provide information concerning the position of
      radioisotope (RI) accumulation and the energy of the photons, it would seem
      reasonable to vary the position and width of the energy window depending on the
      type of RI and the energy resolution of the detector to collect as many of the
      primary photons as possible. We propose a method for determining energy window
      width and position for scintigraphic imaging to collect as many of the primary
      photons as possible, and studied the influence on the Triple Energy Window (TEW)
      scatter compensation method of setting such energy window levels for 99mTc
      (single photopeak) and 201Tl (multiple photopeaks) using detector with different
      energy resolution through simulation. The Monte Carlo simulations were verified
      by comparing the regional energy spectrum at the phantom obtained from the
      simulation against experimental measurements. The energy window with our proposed
      method for 99mTc is 20% and 47.3% for 201Tl using gamma camera, and 9.8% for
      99mTc using a semiconductor detector with a theorized energy resolution of 7.0
      keV.

PMID- 9567030
TI  - [Effect of attenuation by the cranium on quantitative SPECT measurements of
      cerebral blood flow and a correction method].
AB  - Attenuation correction for cerebral blood flow SPECT image reconstruction is
      usually performed by considering the head as a whole to be equivalent to water,
      and the effects of differences in attenuation between subjects produced by the
      cranium have not been taken into account. We determined the differences in
      attenuation between subjects and assessed a method of correcting quantitative
      cerebral blood flow values. Attenuations by head on the right and left sides were
      measured before intravenous injection of 123I-IMP, and water-converted diameters
      of both sides (Ta) were calculated from the measurements obtained. After
      acquiring SPECT images, attenuation correction was conducted according to the
      method of Sorenson, and images were reconstructed. The diameters of the right and
      left sides in the same position as the Ta (Tt) were calculated from the contours
      determined by threshold values. Using Ts given by 2Ts = Ta - Tt, the correction
      factor gamma = exp (mu(1)Ts) was calculated and multiplied as the correction
      factor when rCBF was determined. The results revealed significant differences
      between Tt and Ta. Although no gender differences were observed in Tt, they were
      seen in both Ta and Ts. Thus, interindividual differences in attenuation by the
      cranium were found to have an influence that cannot be ignored. Inter-subject
      correlation is needed to obtain accurate quantitative values.

PMID- 9567031
TI  - [Quantification of regional cerebral blood flow at the control state and loaded
      with diamox using split-dose 99mTc-ECD SPECT and venous blood samples].
AB  - The purpose of the study is to develop a simple and less invasive method for
      quantifying regional cerebral blood flow (rCBF) at pre- and post Diamox test
      using split-dose 99mTc-ECD and SPECT. By employing a microsphere model, integral
      of input function was calculated by the one-point venous sampling method
      previously reported. The study was performed on 5 subjects with cerebrovascular
      diseases. A split dose of 99mTc-ECD was injected pre- and post Diamox injection,
      and rCBF was measured by two SPECT scans and single venous samples, respectively.
      Mean CBF obtained by the present method was 0.47 +/- 0.07 ml/g/min at the control
      state, and 0.63 +/- 0.12 ml/g/min loaded with Diamox (mean % increase; 35%),
      showing good agreement with those obtained by the 133Xe-inhalation method. Since
      the present method does not require arterial blood sampling, dynamic data
      acquisition and dose corrections, it is simple, less invasive and useful in
      clinical SPECT studies.

PMID- 9567032
TI  - [Automatic calculation of left ventricular volume and ejection fraction from
      gated myocardial perfusion SPECT--basic evaluation using phantom].
AB  - We evaluated accuracy of Quantitative Gated SPECT Program that enabled
      calculation of the left ventricular (LV) volume and ejection fraction by
      automatically tracing the contour of the cardiac surface. Cardiac phantoms filled
      with 99mTc-solution were used. Data acquisition was made by 180-degree projection
      in L type and 360-degree projection in opposed type. Automatic calculation could
      be done in all processes, which required 3-4 minutes. Reproducibility was
      sufficient. The adequate cut off value of a prefilter was 0.45. At this value LV
      volume was 93% of the actual volume in L type acquisition and 95.9% in opposed
      type acquisition. The LV volume obtained in L type was smaller than that obtained
      in opposed type (p < 0.05). The tracing of the defects was fair, on the cardiac
      phantoms with all of 90-degree defects and 180-degree defects of the septal and
      lateral wall. The LV volume was estimated to be larger on the phantom with 180
      degree defect of the anterior wall, and to be smaller on the phantom of 180
      degree defect of the inferoposterior wall. Because tracing was deviated
      anteriorly at the defects. In the patients with similar conditions to 180-degree
      defect of the anterior wall or inferoposterior wall, the LV volume should be
      carefully evaluated.

PMID- 9567033
TI  - [Simple kinetic analysis of 99mTc-GSA by direct integral linear least square
      regression method: calculation of hepatic blood flow and receptor index based on
      three-compartment model].
AB  - To obtain both hepatic blood flow and an index of asialoglycoprotein receptor
      amount by simple calculation in the asialoglycoprotein receptor imaging with
      99mTc-DTPA-Galactosyl Human Serum Albumin (99mTc-GSA), we have tested the
      applicability of the direct integral linear least square regression (DILS) method
      based on a linear 3-compartment model (Bronqvist, 1984) to the kinetic analysis
      of 99mTc-GSA scintigraphy. DILS method can provide hepatic blood flow (k1) and
      the product of receptor amount and forward binding rate constant (k1k3/k2) as a
      receptor index, without requiring iterative calculation and initial estimates of
      the parameters. To compare DILS method with nonlinear least square regression
      (NLS) method as a standard, data from 35 patients with liver dysfunction were
      analyzed by both methods. The effect of the data noise to parameter estimate were
      simulated, and both DILS and NLS method could provide reliable parameter estimate
      which is relatively insensitive to the data noise. In estimated model parameters,
      both hepatic blood flow (k1) and the receptor index (k1k3/k2) showed significant
      correlation between 2 methods (r2 = 0.96, p < 0.0001; r2 = 0.99, p < 0.0001,
      respectively). We concluded that DILS method was comparable to NLS method in
      determination of the model parameters and could be useful in the
      asialoglycoprotein receptor imaging.

PMID- 9567034
TI  - [Cerebral kinetics of brain perfusion agents].
AB  - Radiotracers called chemical microsphere are widely accepted as brain perfusion
      agents. Following the intravenous administration, these drugs are transported via
      the artery to the brain, cross the intact blood-brain barrier, and enter the
      brain tissue. Once the tracer flows into the brain, the efflux of the tracer is
      prevented by some trapping mechanism, resulting in prolonged retention. Because
      the distribution of the accumulated tracer remains approximately consistent with
      regional cerebral blood flow for a relatively long period, high-quality SPECT
      images reflecting the distribution pattern of cerebral blood flow can be
      acquired. However, unlike true microsphere, cerebral kinetics of the brain
      perfusion agents is complicated, and various causes may produce discrepancy
      between the distributions of the tracer and blood flow. In this review, cerebral
      kinetics of the brain perfusion agents used commonly is discussed. The knowledge
      of the mechanism of brain accumulation appears to be essential to appropriately
      determine the tracer of choice and interpret the obtained images.

PMID- 9567035
TI  - [Eighty cases of minimally invasive direct coronary artery bypass grafting].
AB  - Between March 1996 and November 1997, 80 patients with a mean age of 70 years (45
      89) have undergone minimally invasive direct coronary artery bypass grafting via
      anterior minithoracotomy or subxiphoid incision with left internal thoracic
      artery and right epigastric artery using local coronary occlusion on a beating
      heart. Cardiac-related hospital mortality was 2.5% (2/80). Routine angiographic
      assessment of anastomotic patency showed an overall patency. rate of 94.6%, but
      demonstrated the severe stenosis at the anastomotic site in 8 patients. Further
      study is required to establish the efficacy of minimally invasive direct coronary
      artery bypass grafting and combination therapy with PTCA.

PMID- 9567036
TI  - [Coronary artery bypass grafting under beating heart without cardiopulmonary
      bypass].
AB  - Recently coronary artery bypass grafting under beating heart without
      cardiopulmonary bypass has been widely accepted for patients with associated
      risks of standard bypass surgery. Between October 1995 and October 1997, we
      performed this procedure on 40 (11 reoperative procedures). There were 26 single
      vessel (9 reoperative procedures), 12 double-vessel (2 reoperative procedures)
      and 2 triple-vessel bypass procedures. Major risk factors and concomitant
      disorders were as follows: chronic hemodialysis, 3; poor renal function, 5; poor
      lung function, 6; reoperative procedure, 11; elder patient (age > or = 75 y), 4.
      Twenty-five patients were operated through a mediansternotomy, 11 through left
      thoracotomy (small thoracotomy 7), 1 through a small right thoracotomy, 3 through
      a laparotomy with the diaphragm approach, 1 through both a left thoracotomy and a
      laparotomy with the diaphragm approach. Fifty-three grafts were used during this
      course (internal thoracic artery [ITA] = 42, gastroepiploic artery [GEA] = 7,
      saphenous vein [SV] = 4) and the sequential bypass was performed with 2 LITA
      grafts. In selected patients this procedure is very safe, cost-effective and
      required less blood loss compared to standard bypass surgery. This procedure was
      considered to be very effective for patient with chronic hemodialysis. Also, left
      thoracotomy (a small thoracotomy) and laparotomy with the diaphragm approach
      showed particular effectiveness to reoperative procedures in order to preserve
      the patent grafts.

PMID- 9567037
TI  - [Clinical experiences of minimally invasive direct coronary artery bypass
      (MIDCAB)].
AB  - From Jan. to Oct. in 1997, we performed 18 minimally invasive direct coronary
      artery bypass (MIDCAB), aged from 45 to 86 years (the mean age of 69 years). They
      had single LAD disease post PTCA failure in 2 patients, and multiple vessel
      disease in 16 patients including left main stenosis in 2 patients. Sixteen
      patients had associated risk factors for using cardiopulmonary bypass, such as
      cerebrovascular disease in 9 patients, calcification of ascending aorta in 5
      patients, renal failure in 2 patients, old age over 80 years in 4 patients and
      cancer in one patient. Single bypass grafting of left internal thoracic artery
      (LITA) to left anterior descending artery (LAD) underwent through left anterior
      small thoracotomy in 9 patients, double bypass grafting of gastroepiploic artery
      or right ITA to right coronary artery with LITA to LAD in 9 patients through
      subxiphoid small incision or right anterior small thoracotomy. The mean number of
      distal anastomosis was 1.5/patient. All patients are alive and asymptomatic, and
      postoperative angiography demonstrated the patency rate of 96.2% (26/27). MIDCAB
      is considered as a justified and safe technique for the patients who are
      ineligible for standard coronary artery bypass grafting.

PMID- 9567038
TI  - [The early results of the minimally invasive direct coronary artery bypass
      (MIDCAB)].
AB  - The clinical experiences of 29 consecutive MIDCAB procedures performed at our
      institution between October, 1996, and October, 1997, were analyzed. Preoperative
      patient's characteristics were as follows; LAD single vessel disease: 25, double
      vessel disease: 1, triple vessel disease: 1, RC single vessel disease: 1, LMT
      lesion: 1, concomitant procedures: 2 (ASO: 1, AAA: 1). LITA harvesting was
      performed using the video-assisted thoracoscopy in initial 4 patients, and in
      last 10 patients we used the specially designed retractor THORALIFT (Autosuture
      Co., Ltd.) for harvesting LITA by direct vision. LAD was stabilized mechanically
      using the stabilizer when we performed the anastomosis in last 10 patients to
      enhance the quality of the anastomosis. The patency rate was 96%, but there were
      two patients (6%) who had the stenosis of the anastomosis site. Coronary artery
      occlusion time was 13.2 minutes in the mean. We also studied the hemodynamics of
      blood flow in LITA grafts with the aid of 7.5 MHz transthoracic duplex imaging in
      these MIDCAB patients and compared with the LITA grafts in conventional CABG
      performed in same periods. There were no statistical differences between the two
      groups about the graft flow and velocity. We conclude that MIDCAB would be an
      alternative procedure that can be performed with low risk and acceptable early
      results in selected patients.

PMID- 9567039
TI  - [Minimally invasive direct coronary artery bypass for ischemic heart disease
      associated with preoperative severe complications].
AB  - Our experiences of minimally invasive direct coronary artery bypass (MIDCAB) were
      reported with review of literatures. Patient #1 was a 69 years-old man with left
      main lesion associated with cerebral infarction and impaired renal function.
      Preoperative CT examination showed calcified ascending aorta. There was no
      significant lesions in the large right coronary artery and the circumflex was
      small. The patient underwent MIDCAB via minithoracotomy on the fourth intercostal
      space with left internal thoracic artery (ITA) to left anterior descending artery
      (LAD). The patient was weaned from ventilator 3 hours after the operation and his
      postoperative course was uneventful. Patient #2 was a 80 years-old man with acute
      myocardial infarction requiring intraaortic balloon pumping (IABP) due to
      significant stenosis in the right coronary artery and left main lesion associated
      with chronic hemodialysis due to renal failure. The right coronary artery was
      dilated by balloon angioplasty at the time of emergency coronary angiogram.
      However, the emergent operation was required because of the left main lesion. The
      circumflex was relatively small and because of severe complication, MIDCAB was
      selected to improve his condition. He underwent MIDCAB via minithoracotomy. The
      heart was enlarged because of congestive heart failure and left inferior
      epigastric artery was used to extend the length of the left ITA. The composite
      graft of ITA and IEA was anastomosed to the LAD under beating heart. The IABP was
      removed 8 hours after the operation and his postoperative course was uneventful.
      The MIDCAB for coronary artery bypass was first reported by Benetti et al in 1995
      and the procedure seemed to be very effective for preventing postoperative
      complications in selected patients as seen in ours.

PMID- 9567040
TI  - [Video-assisted mammary harvest technique with harmonic scalpel].
AB  - We have developed a video-assisted mammary harvest technique using the Harmonic
      Scalpel. The clinical method and results are reported here. Since Nov. 1995, 70
      left and 5 right internal mammary arteries (L/RIMAs) were taken down
      thoracoscopically and utilized for minimally invasive coronary artery bypass
      grafting. Each of the IMAs was harvested up to the upper margin of the first rib
      or higher and down to the bifurcation. Coagulation and cutting of the branches
      were achieved with excellent hemostasis using only the Harmonic Scalpel with a
      hook dissector. A CO2 insufflation technique with 8-10 mmHg of intrathoracic
      pressure safely improved visualization of the IMA in each case. The mean
      operative time was 65 minutes (range 45-95) for the left and 35 minutes (range 25
      45) for the right. All the pedicled IMAs but one which was lost due to intimal
      dissection had satisfactory free flows. Video-assisted mammary harvest can be
      accomplished with insufflation technique and facilitated by using the Harmonic
      Scalpel with a hook dissector.

PMID- 9567041
TI  - [Efficacy of the MIDCAB doughnut: a new instrument for immobilization and
      hemostasis during MIDCAB].
AB  - A new instrument for the immobilization and hemostasis of an anastomotic site
      during off-pump bypass is described. The instrument called "MIDCAB doughnut" was
      used safely and accurately in 31 patients who underwent MIDCAB without CPB. In
      these, the instrument was applied in 44 anastomotic sites on the beating heart
      (30 left anterior descending, 7 right coronary, and 7 obtuse marginal arteries).
      It can make an operative field motionless and bloodless without distal snaring,
      because of air sucked fixation of an entire circuit of the anastomotic site.
      There was no operative and hospital deaths. Postoperative angiography revealed a
      100% patency rate of the grafts. MIDCAB doughnut can improve a quality of the
      anastomosis during beating bypass surgery.

PMID- 9567042
TI  - [Minimally invasive direct coronary artery bypass grafting (MIDCAB) for right and
      circumflex coronary artery systems].
AB  - BACKGROUND: Single-vessel coronary bypass grafting of the left internal thoracic
      artery (LITA) to the left anterior descending coronary artery (LAD) with mini
      thoracotomy has been shown to produce excellent results with almost no mortality.
      However this procedure cannot be used in patients with double or triple vessel
      disease. METHODS: Between Aug. 96 and Dec. 97, 17 pts underwent minimally
      invasive direct coronary artery bypass (MIDCAB) to right (RCA) and circumflex
      coronary artery (CX). LITA and RITA were thoracicscopically harvested and the
      right gastroepiploic artery (RGEA), inferior epigastric artery, and radial artery
      were then harvested. A limited left thoracotomy in combination with limited
      anterior right thoracotomy (n = 3) or right lower parasternal incision extending
      to below the xiphoid process (n = 6) were made. The double MIDCAB as performed in
      16 pts and triple in 1 pt. RESULTS: There was no operative death. At follow up,
      all pts are alive and well. The postoperative angiographic studies showed 30/31
      grafts were patent. CONCLUSION: The utility of multi-vessel MIDCAB for the LAD,
      CX and RCA with in-site arterial grafts has been demonstrated in the present
      study. This less invasive surgical technique may become a viable option for the
      management of multi-vessel coronary artery disease.

PMID- 9567043
TI  - [A case report of pre-operative simultaneous angiography of the LITA and LAD for
      MIDCAB surgery].
AB  - The patient was 59-year-old man, who had a 90% stenotic lesion of LAD (seg 6,
      just proximal). We performed minimally invasive direct coronary artery bypass
      (MIDCAB) surgery. At preoperative angiography, we took a photo of the
      posteroanterior view which is equivalent to position of an operation. Also,
      photos of the LITA and LAD were taken simultaneously. This simultaneous
      angiography was useful for deciding on the skin incision line. During the
      postoperative angiography, it was recognized that the skin incision line existed
      at the middle of the LITA and anastomotic point. In MIDCAB surgery, to obtain a
      good operative view could have an influence on the difficulty of the operation
      and effect the results of the operation. Therefore, our new angiographic
      technique is though to be useful for new surgical technique (MIDCAB).

PMID- 9567044
TI  - [A case of MIDCAB to the left circumflex via the left posterolateral
      thoracotomy].
AB  - There have been many reports of MIDCAB to left anterior descending artery via a
      small dissection utilizing the left anterolateral thoracotomy. We report here a
      case of CABG reoperation to the circumflex artery by MIDCAB via the left
      posterolateral thoracotomy. A 66-year-old male patient had received a 3 branch
      bypass graft on the LITA-LAD and the SVG-OM-4 PD at another institution.
      Postoperative angiography revealed a SVG occlusion. Since repeated intervention
      was unsuccessful, reoperation was necessary. To preserve the patency of the LITA,
      the 4th left intercostal posterolateral thoracotomy was selected. We utilized a
      commercially available rib retractor for MIDCAB, as well as a stabilizer and a
      CO2 blower to obtain a nearly perfect bloodless stabilized view. A new SVG was
      used to connect the left circumflex artery. The operation was successful without
      any postoperative complications or need for transfusion. After a two week
      hospital stay, the graft patency was confirmed and the patient was discharged.

PMID- 9567045
TI  - [Pitfall of minimally invasive direct coronary artery bypass].
AB  - Six thoroughly selected patients underwent minimally invasive direct coronary
      artery bypass grafting (MIDCAB). While monitoring left ventricular function with
      transesophageal echocardiography, MIDCAB was done by performing small left
      thoracotomy through the fourth intercostal space, dissection of the left internal
      thoracic artery without thoracoscopy, ischemic preconditioning, and grafting of
      the internal thoracic artery to the left anterior descending coronary artery with
      8-0 polypropylene continuous suture. A home-made cardiac stabilizer and Visuflow
      enabled us to perform precise suturing of the internal thoracic artery. The
      patency of all grafts was confirmed by early transthoracic Doppler
      echocardiography and selective angiography. A new stenosis of the coronary artery
      distal to the anastomosis was detected probably due to coronary snaring in one
      patient. The anastomosis sites were confined to the distal segments of the left
      anterior descending coronary artery in MIDCAB patients. The optimal anastomosis
      site may be missed in the patients with proximal left anterior descending artery
      disease. An experimental study of myocardial tissue oxygen saturation using near
      infrared spectroscopy showed that two times of coronary occlusion and reperfusion
      provided satisfactory effects of ischemic preconditioning. Measurement of the
      myocardial tissue oxygen saturation may be helpful for confirming effective
      ischemic preconditioning and a safe coronary occlusion during MIDCAB. Although
      MIDCAB is an attractive procedure, we should consider the accuracy of
      anastomosis, the risk of possible incomplete revascularization, the indications,
      and long-term results.

PMID- 9567046
TI  - [Pitfalls and their solution in MIDCAB].
AB  - Between July 1996 and September 1997, 11 patients underwent coronary artery
      bypass starting with left anterior small thoracotomy. All patients were evaluated
      with Electron Beam Computed Tomography (EBCT) preoperatively. Two patients out of
      11 required conversion to sternotomy due to inadequate length of left internal
      mammary artery (LIMA) graft. One patient had a graft occlusion and underwent
      reoperation, when a graft avulsion was identified. Distance between LIMA and LAD
      by EBCT highly predicted needs of procedure modification to obtain additional
      length of graft. We demonstrated anterior pericardiopexy as an additional
      technique for protecting LIMA graft from abnormal tension. We conclude that it is
      crucial to harvest adequate length of LIMA in MIDCAB and anterior pericardiopexy
      may be useful to prevent a graft avulsion.

PMID- 9567047
TI  - [A study of minimally invasive direct coronary artery bypass (MIDCAB): comparison
      of low risk group and high risk group].
AB  - We started to perform MIDCAB for the cases of markedly low cardiac function from
      June, 1996 and obtained satisfactory results. So we expanded the indications to
      include only left anterior descending artery (LAD) lesion from June, 1997 and
      have since performed this operation on 14 cases. The 14 cases of MIDCAB were
      divided into two groups, Group L consisting of 6 low risk cases: 1 lesion alone
      without any complications involving other organ before operation and Group H made
      up of 8 high risk cases: multi branch lesion but rated as high risk because of
      the extracorporeal circulation being used. Both Group L and Group H were free of
      operation death and hospital death. In Group L, all the cases underwent operation
      without blood transfusion, the period of postoperative stay in ICU was not longer
      than 1 day, on catecholamine was required after operation and complications were
      not found either. The patency of the graft was 100 percent. The patients were
      discharged 13.7 days after operation. In Group H, 2 cases required blood
      transfusion and 3 cases required catecholamine after operation. Complication
      arising from operative wound were noted in 3 cases. One GEA graft to the right
      coronary artery and one LITA to the LAD buried in the muscle were occluded. After
      operation, hospital stay for 23.9 days was required. In Group L, the
      postoperative course was excellent, so MIDCAB was considered indicated well for
      this group. In Group H too, the selection of MIDCAB was considered adequate that
      the risk of conventional CABG is considered much higher.

PMID- 9567048
TI  - [MIDCAB procedure by original stabilizer and usual devices].
AB  - The key of MIDCAB is how to stabilize the left anterior descending artery. We
      introduce our MIDCAB procedure by using our original stabilizer and usual devices
      in this paper. METHOD: Between March 1997 and August 1997, 13 patients underwent
      left internal thoracic artery to left anterior descending artery
      revascularization without extracorporeal circulation, and one case underwent
      right internal thoracic artery to right coronary artery. In all cases, we exposed
      the internal thoracic artery through a 8 cm anterior fifth space thoracotomy. One
      case of MIDCAB to right coronary artery was added an inferior hemisternotomy for
      anastomosis to the right coronary artery. The internal thoracic artery was
      harvested by using the Kent retractor. The anastomosis were done by using our
      original stabilizer and retract O tapes. RESULTS: In our method, there was no
      mortality and no postoperative cardiac event. There were 5 postoperative
      complications, one was reoperation due to bleeding from a branch of the internal
      thoracic artery, two cases were wound infection. Cerebral infarction, bleeding
      due to urinary bladder tumor and lumbar compression fracture was seen in one case
      each. CONCLUSION: MIDCAB procedure was performed safety and effectively by using
      our original stabilizer and usual devices.

PMID- 9567049
TI  - [A case of synchronous resection of double cancers in the lung and stomach
      through median sternotomy and abdominal incision].
AB  - A 72-year-old male was admitted to our clinic for the treatment of early stomach
      cancer. A chest X-ray film on admission showed a mass in the right lung field. CT
      scan and transbronchoscopic lung biopsy revealed lung cancer (C-T2N2M0-stage
      IIIA). Histologically it was poorly differentiated adenocarcinoma, which was
      different from stomach cancer. We underwent synchronous resection of this double
      cancer through median sternotomy and abdominal incision. We conducted lobectomy,
      bilateral mediastinal lymph node dissection, and wedge resection of stomach.
      Postoperative diagnosis was early lung cancer (p-T2N0M0-stage I) and advanced
      stomach cancer (A-IIc+IIa advanced t2 (mp) n1H0P0M0-stage II). Postoperative
      course was stable and the patient was healthy at present. As such, this case
      report suggests that synchronous double cancers involving the lung and stomach,
      if both cancer are early stage, should be resected synchronously.

PMID- 9567050
TI  - [A case of Poland's syndrome with giant bulla resected by using autologous fascia
      lata].
AB  - We reported a case of giant bulla with Poland's syndrome, only left pectoral
      major and minor muscles defect. A 58-year-old man was admitted to our hospital
      with shortness of breath on exertion. Computed tomographic scan revealed right
      giant bulla in emphysematous lung. The giant bulla was resected by linear stapler
      with autologous fascia lata. Though minor air leakage persisted for 5
      postoperative days, the postoperative course was uneventful. It could be
      effective to reinforce staple line by using autologous fascia lata in
      emphysematous bulla without any infectious problem.

PMID- 9567051
TI  - [Ideal production of the magnifying glass for the coronary artery bypass
      surgery].
AB  - In recent year, the number of coronary artery bypass grafting (CABG) has been
      increased more than 10,000 cases in the year of 1996 in Japan. However, it is
      very important to use a magnifying glass in CABG, especially for the anastomosis
      of small-caliber vessels, and to get high patency rate in the long-term. There is
      no ideal magnifying glass to be available during operation for CABG in the world
      wide. Therefore, I have produced it with some ideal considerations in the
      standpoints of from the availability, lightness, and cost performance which will
      be soon commercially available.

PMID- 9567052
TI  - [Open heart surgery in patients with a tracheostoma].
AB  - From April 1992 to May 1997 six patients underwent open heart surgery, who had
      tracheostoma at the time of operation. The sternum was divided completely in
      three patients whose tracheostoma lay highly on the neck, and it was cut
      transversely on the manubrium at the level of the first intercostal space, below
      which it was split longitudinally in two patients (partial median sternotomy). In
      one patient right anterolateral thoracotomy was used. There were no operative
      death and no complication related to infection. A left internal thoracic artery
      (LITA) was used successfully for a bypass conduit in two patients who underwent
      partial median sternotomy. Dissection of the proximal portion of the LITA through
      the second intercostal space prior to the sternotomy made the graft procurement
      feasible in this particular situation. In conclusion, full-length sternotomy is
      performable safely when the tracheostoma lies highly on the neck, and the partial
      sternotomy up to the midmanubrium is applicable, including LITA harvesting, even
      if it is just at the sternal angle.

PMID- 9567053
TI  - Assessing placebo response using Bayesian hierarchical survival models.
AB  - The National Institute of Mental Health (NIMH) Collaborative Study of Long-Term
      Maintenance Drug Therapy in Recurrent Affective Illness was a multicenter
      randomized controlled clinical trial designed to determine the efficacy of a
      pharmacotherapy for the prevention of the recurrence of unipolar affective
      disorders. The outcome of interest in this study was the time until the
      recurrence of a depressive episode. The data show much heterogeneity between
      centers for the placebo group. The aim of this paper is to use Bayesian
      hierarchical survival models to investigate the heterogeneity of placebo effects
      among centers in the NIMH study. This heterogeneity is explored in terms of the
      marginal posterior distributions of parameters of interest and predictive
      distributions of future observations. The Gibbs sampling algorithm is used to
      approximate posterior and predictive distributions. Sensitivity of results to the
      assumption of a constant hazard survival distribution at the first stage of the
      hierarchy is examined by comparing results derived from a two component
      exponential mixture and a two component exponential changepoint model to the
      results derived from an exponential model. The second component of the mixture
      and changepoint models is assumed to be a surviving fraction. For each of these
      first stage parametric models sensitivity of results to second stage prior
      distributions is also examined.

PMID- 9567054
TI  - Generalized additive models for current status data.
AB  - Current status data arise in studies where the target measurement is the time of
      occurrence of some event, but observations are limited to indicators of whether
      or not the event has occurred at the time the sample is collected--only the
      current status of each individual with respect to event occurrence is observed.
      Examples of such data arise in several fields, including demography,
      epidemiology, econometrics and bioassay. Although estimation of the marginal
      distribution of times of event occurrence is well understood, techniques for
      incorporating covariate information are not well developed. This paper proposes a
      semiparametric approach to estimation for regression models of current status
      data, using techniques from generalized additive modeling and isotonic
      regression. This procedure provides simultaneous estimates of the baseline
      distribution of event times and covariate effects. No parametric assumptions
      about the form of the baseline distribution are required. The results are
      illustrated using data from a demographic survey of breastfeeding practices in
      developing countries, and from an epidemiological study of heterosexual Human
      Immunodeficiency Virus (HIV) transmission.

PMID- 9567055
TI  - A method to compare two samples of recurrence data.
AB  - This paper presents a nonparametric comparison of two samples of units subject to
      recurrent events. The method is illustrated with applications to the repair of
      locomotive braking grids and to recurrent bladder tumors in patients.

PMID- 9567056
TI  - Model misspecification effects within a family of alternative discrete
      reliability-growth models.
AB  - We describe a family of related discrete reliability-growth methodologies
      potentially applicable to one-shot systems undergoing a test-analyze-and-fix
      development process. The common feature shared by the models is their connection
      to Duane's renowned learning-curve property. The major difference, however, lies
      in their applicability in the context of two intrinsically different sampling
      schemes. For each model, a summary of the statistical properties of various
      estimators of the parameters as well as the reliability of the system, are
      reported. For purposes of assessing model misspecification, a particular text
      execution scenario conforming to a inverse sampling scheme is adopted. In
      reliability applications, it is not an uncommon practice to borrow inference
      results from models which are inappropriate in this setting. A detailed study of
      the potential impact of such misspecification on the estimation of system
      reliability is presented.

PMID- 9567057
TI  - Identity for the NPMLE in censored data models.
AB  - We derive an identity for nonparametric maximum likelihood estimators (NPMLE) and
      regularized MLEs in censored data models which expresses the standardized maximum
      likelihood estimators in terms of the standardized empirical process. This
      identity provides an effective starting point in proving both consistency and
      efficiency of NPMLE and regularized MLE. The identity and corresponding method
      for proving efficiency is illustrated for the NPMLE in the univariate right
      censored data model, the regularized MLE in the current status data model and for
      an implicit NPMLE based on a mixture of right-censored and current status data.
      Furthermore, a general algorithm for estimation of the limiting variance of the
      NPMLE is provided.

PMID- 9567058
TI  - [What effect does using the Latham devices have on craniofacial growth in uni-
      and bilateral lip-jaw-palate clefts].
AB  - Primary gingivoperiosteoplasty according to Millard consists of active
      presurgical orthopedic treatment with the Latham device at the age of 4 months
      and surgical covering of the alveolar cleft by local mucoperiosteum flaps at the
      age of 6 months. The aim of this investigation was to evaluate the facial growth
      following use of the Latham device. Lateral head X-rays and plaster casts from
      146 patients with unilateral and bilateral clefts of lip and palate were
      investigated (follow-up of 16 years). Ninety-one of these patients formed the
      control group and received no Latham device and no gingivoperiosteoplasty. The
      same surgeon and orthodontist treated all of the 146 patients. Three-dimensional
      growth disturbance was observed after application of the Latham device and
      gingivoperiosteoplasty. Forty-two percent of patients with UCLP and 40% patients
      with BCLP had an "open bite" following closure of the alveolar cleft (control
      group 5%-10%): the length of the upper jaw was shorter than in the control group
      and the frequency of cross-bite was higher. These results demonstrate that
      treatment with a Latham device followed by gingivoperiosteoplasty disturbs facial
      growth. Therefore this treatment should be rejected.

PMID- 9567060
TI  - [Diagnostic pitfalls in benign and malignant salivary gland diseases. Their
      significance for prognosis and therapy].
AB  - Diagnostic pitfalls exist when benign salivary gland diseases are mistakenly
      classified as malignant, with consequences for treatment and prognosis. Examples
      are necrotizing sialometaplasia, metaplastic Warthin tumour and sclerosing
      polycystic sialadenopathy. The proper diagnosis is of eminent importance to
      distinguish cases of primary tumours that have developed in salivary glands or
      their lymph nodes from cases of extraglandular tumours with metastases in these
      glands or their nodes. In these cases clinical data and additional
      immunocytochemical methods are necessary to clarify the exact diagnosis,
      especially when the primary salivary gland tumours have a structure largely
      identical to the metastases (e.g. squamous cell carcinoma). Nasopharyngeal or
      cervical chordomas can be mistaken for pleomorphic adenoma or mucinous
      adenocarcinoma. The initial stage of malignant MALT lymphomas in association with
      Sjogren's syndrome demands identification of clonal rearrangement for therapeutic
      implication. The diagnostic criteria for proper classification are analysed in
      detail.

PMID- 9567059
TI  - [Squamous epithelial carcinoma in a 27-year-old patient with cellular immune
      defect].
AB  - Squamous cell cancer of the oral cavity mainly occurs in older patients or in
      patients with alcohol or nicotine abuse. Younger patients are seldom involved.
      The case of a 27-year-old woman with a squamous cell cancer of the right cheek
      will be presented. Without any risk factors, an immune defect resulting in
      chronic Candida infection of the oral cavity seems to be responsible for the
      carcinogenesis.

PMID- 9567061
TI  - [Quality of cardiopulmonary resuscitation by dentists in dental emergency care].
AB  - The crucial factor deciding the success of cardiopulmonary resuscitation is a
      sufficient oxygen supply. At about 4 min after cardiac arrest, cerebral death
      results because of hypoxia, and cardiopulmonary resuscitation has to be started
      regardless of the pathogenesis of the cardiac arrest. The purpose of the study
      was to assess the application of guidelines for cardiopulmonary resuscitation by
      participants at a dental surgery congress (n = 96) and to evaluate previous
      knowledge in cardiopulmonary resuscitation and knowledge after instruction. The
      present study was based on the standards and guidelines for cardiopulmonary
      resuscitation issued by the American Heart Association. The group was divided
      into four groups of doctors experienced or inexperienced in clinical emergencies
      or with dummies. For the study the Skillmeter-ResusciAnne (Laerdal, Stavanger,
      Norway) was used, which has automatic data recording. After analysis of the
      individual errors, the success of new instruction was assessed. Good previous
      knowledge was registered, particularly with respect to checking respiration and
      hyperextension of the head (67.7%), primary insufflation (93.8%), closed-chest
      cardiac massage (99%) and correct compression rate (68.4%). The participants
      demonstrated post-instruction improvement in all subdivisions except in the group
      without practice on dummies (primary insufflation: from 94.4 to 88.9%; correct
      order of checking consciousness and respiration, primary insufflation, the
      carotid pulse and closed-chest cardiac massage: from 22.2 to 5.6%). Good results
      with marked improvements in the second passage were achieved in checking
      consciousness and the carotid pulse, closed-chest cardiac massage and correct
      implementation of compression. The participants were, however, found to be in
      need of further education and training in diagnostics and certain cardiopulmonary
      resuscitation measures. Knowledge should be improved concerning recognition of
      the emergency (42.7%), checking the carotid pulse (22.9%), the correct order of
      primary insufflation and closed-chest cardiac massage (9.4%), correct
      implementation of compression (21.8%) and ventilation (36.4%), and the correct
      ratio of compression and ventilation (21.9%). Regular courses should be targeted
      at these specific aspects.

PMID- 9567063
TI  - [Histotomography studies of direct radiogenic dental enamel changes].
AB  - OBJECTIVE: The volume of literature on radiation-induced caries is still
      inconsistent as regards the state of the art. Our histotomographic studies have
      shown direct radiogenic effects on the dentoenamel junction (atrophy of the
      odontoblast processes). Whether there are direct effects of radiation on dental
      enamel is not yet known. MATERIAL AND METHOD: Sound teeth (group 1, n = 10) were
      compared either with enamel specimens after high dose in vitro radiation (500
      2500 Gy; group 2; n = 10) and after experimental enoral in situ irradiation (60
      Gy; group 3; n = 20), or with teeth from patients after cancer radiotherapy (36
      Gy; group 4; n = 20) and with teeth which had obviously decayed due to cancer
      radiotherapy (60 Gy; group 5; n = 20). Vestibular enamel surfaces of the teeth
      were exposed to identical in vitro demineralizations (lactic acid gel; pH = 5.0).
      Each of the samples was prospectively studied histologically by confocal laser
      scanning microscopy (CLSM) after 90, 180 and 270 min of acid interaction. Data
      were interpreted micromorphometrically (width of the demineralized area) and
      micromorphologically. RESULTS: The width of the demineralized area varies between
      the two in vivo irradiated groups of specimens (group 4: P < 0.01; group 5: P <
      0.001) and the high dose in vitro irradiated teeth (P < 0.01) and is
      significantly different from the sound controls. The histological image of the
      demineralization in subsurface areas in the teeth of radiotherapy patients is
      characterized by a total loss of the prismatic structure (homogeneously,
      amorphous substance). CONCLUSIONS: Direct radiogenic effects at the dentoenamel
      junction have been described earlier. The additional information offered by this
      study is that there are significant micromorphometric differences in the
      demineralizing behaviour of irradiated enamel. Obviously, enamel is less
      resistant to acid attack after irradiation.

PMID- 9567062
TI  - [Withdrawal therapy of patients with alcoholism and nicotine dependence with
      carcinomas in the area of the head and neck. Luxury or necessity?].
AB  - PURPOSE: Alcohol and nicotine abuse play a major role in the etiology of oral
      squamous cell carcinomas. In the present study, we investigated the number of
      patients with oral/oropharyngeal carcinomas who regularly consume alcohol and
      nicotine and what type of specific treatment should be prescribed for the
      addiction. PATIENTS AND METHOD: A total of 105 patients (90 men, 15 women) with
      oral/oropharyngeal squamous cell carcinomas were studied based on catamnestic
      data as well as a special questionnaire designed to assess drinking and smoking
      habits (40 g alcohol/day for men and 20 g alcohol/day for women was taken as the
      standard measure for those considered at risk for alcoholism). For smokers, the
      number of packs smoked per year was determined and compared to clinical data
      (i.e., tumor size, location) and laboratory data (gamma-GT). Particular attention
      was given to the addiction behavior before and after tumor therapy (recorded at
      least 1 year after successful tumor treatment). RESULTS: At the time of
      diagnosis, 83.1% regularly drank alcohol (71.9% reported drinking over 40 g/ 20 g
      of alcohol per day). Another 17.9% stopped drinking after therapy. Of the
      alcoholics 59.8% had been exposed to a daily consumption level above the
      threshold amount for more than 20 years. Some 70% of the patients reported that
      they exclusively drank beer. Tobacco consumption came from cigarette smoking
      92.7% and 89.7% reported that they smoked before therapy--after therapy only
      37.8% smoked. Carcinomas of the floor of the mouth indicated a prevalence toward
      alcohol and nicotine abuse. Of the patients with a T3 and T4 carcinoma 84% had
      daily alcohol consumption levels over the threshold value stated above. None of
      the 105 patients underwent specific alcohol treatment therapy. CONCLUSION: In
      light of the high prevalence of carcinomas of the oral cavity in patients with
      alcohol and nicotine addiction, mandatory withdrawal therapy should be offered in
      the form of postoperative treatment to prevent recurrence or the development of
      second primary tumors, as well as to improve the quality of life and encourage
      social rehabilitation. Before further treatment, for example, with retinoids, a
      successful withdrawal treatment should be completed.

PMID- 9567064
TI  - [Stereolithography models vs. milled 3D models. Production, indications,
      accuracy].
AB  - Anatomic, life-like, three-dimensional models have a definite place in cranio
      maxillofacial surgery. Our experience with 541 computer tomographic (CT)-based
      three-dimensional (3D)-models for diagnostic purposes, preoperative planning and
      model operations in our department was gained using stereolithographic and milled
      models. The question of which production method is preferable is a matter of
      controversy in the literature. Both methods are based on CT and magnetic
      resonance imaging data, but the differences in production give rise to specific
      advantages and disadvantages. For comparison we scanned two measurement models,
      fabricated milled and stereolithographic models, and analyzed the differences
      concerning accuracy and shape of specific structures. The scan distance (feed) is
      the limiting factor for the accuracy for both methods. Milled models show the
      highest precision in the plane of CT scanning--the more oblique the measurements
      became to this plane, the greater the decrease in accuracy. Hollows and undercuts
      can only be produced by splitting the model. Stereolithographic models show
      higher deviations with randomly distributed errors. The mean deviation was 0.81
      mm on stereolithography and 0.54 mm on milled models. The accuracy of both
      methods is sufficient for clinical use. In routine cases the milling method seems
      to be superior because of shorter production time and lower costs. In special
      cases, where hollows and fine structures play a major role, stereolithography is
      the method of choice.

PMID- 9567065
TI  - [Natural coral calcium carbonate as alternative substitute in bone defects of the
      skull].
AB  - A biomaterial derived from natural corals with surgical applications is the
      calcium carbonate Biocoral. Since 1992 the author has been using this material as
      a bone graft substitute in maxillofacial surgery. Eighty-nine clinical
      implantations were done in 68 patients for different indications. The results
      suggested that coral grafts are well tolerated and are simultaneously partially
      ossified as the calcified skeleton is resorbed. Clinical cases show that use of
      this material has been successful.

PMID- 9567066
TI  - [Some current comments on online media].

PMID- 9567067
TI  - [Decision of the Zweibrucken Federal Court on oral surgery].

PMID- 9567068
TI  - [Oral Langerhans cell granulomatosis simulating necrotizing gingivostomatitis].
AB  - An unusual case of nonhealing necrotizing gingivostomatitis in a 66-year-old man
      is described. Microscopic examination of biopsy material showed an infiltrate of
      Langerhans cells. Merely oral lesions of Langerhans cell granulomatosis-
      especially in an old person--occur very seldom.

PMID- 9567069
TI  - [Sairei-to inhibits the production of endothelin-1 by nephritic glomeruli(2):
      alisols, possible candidates as active compounds].
AB  - We have previously reported that Sairei-to (TJ-114), a Japanese herbal medicine,
      prevented the production of endothelin-1 in anti-GBM nephritic rats, and that
      Alismatis Rhizoma (Takusha in Japanese), one of the twelve herbs composing TJ
      114, might be responsible for the action. In order to further clarify the
      antinephritic components of TJ-114, we investigated the effects of Takusha
      extracts on various parameters, including endothelin-1 production of glomeruli in
      vitro and in vivo using anti-GBM nephritic rats. MeOH-100% MeOH and MeOH-50% MeOH
      fractions (31.3 microgram/ml or higher) strongly inhibited an increase in
      endothelin-1 concentration in culture medium when they were added to a culture of
      glomerular cells derived from nephritic rats. In addition, oral administration of
      the MeOH-100% MeOH fraction (30 mg/kg) ameliorated the proteinuria, increase in
      systolic blood pressure and changes in histopathological parameters in nephritic
      rats. Oral administration of the MeOH-100% MeOH fraction inhibited increase in
      endothelin-1 expression in the glomeruli of nephritic rats and in endothelin-1
      production by a culture of glomerular cells derived from the nephritic rats.
      Alisols A and B, the main constituents of the MeOH-100% MeOH fraction, inhibited
      in vitro endothelin-1 production by glomerular cells derived from the nephritic
      rats. Oral administration of alisol B (30 mg/kg) prevented the endothelin-1
      expression by glomeruli and the increase in endothelin-1 production by cultured
      nephritic glomerular cells. Oral administration of alisol B also ameliorated the
      proteinuria, the increase in systolic blood pressure and the changes in
      histopathological parameters in the nephritic rats. These results indicate that
      the antinephritic action of TJ-114, resulting from the inhibition of endothelin-1
      production, may be attributed to the alisols in Takusha.

PMID- 9567070
TI  - [Intracranial aneurysms in autosomal dominant polycystic kidney disease detected
      by MR angiography: screening and treatment].
AB  - The association of intracranial aneurysm with ADPKD is well-known, and patients
      with ADPKD are at increased risk of subarachnoid hemorrhage from rupture of
      intracranial aneurysms. We prospectively performed three-dimensional time-of
      flight magnetic resonance angiography (MRA) in 30 nonselective adult patients
      with ADPKD. Sixteen were women and 14 were men with a mean age of 51 yr (range 24
      to 79 yr). The diagnosis of ADPKD was made on the basis of abdominal ultrasound
      or computed tomographic studies. Three patients were on maintenance hemodialysis,
      8 patients were nondialysed patients with chronic renal failure (serum creatinine
      > or = mg/dl) and 25 patients had hypertension (BP > or = 140/90 mmHg). None of
      these patients have a previous diagnosis of intracranial aneurysm. Unruptured
      intracranial aneurysms were suspected in 5 patients by MRA, and 8 aneurysms were
      confirmed in 4 (13.3%) of 30 patients by conventional arteriography. These
      aneurysms were 3 approximately 10 mm in diameter and 3 aneurysms (3 approximately
      4 mm in diameter) were newly detected by cerebral arteriography. After informed
      consent was obtained, neck clipping of the intracranial aneurysms were performed
      successfully in all the patients. These results suggest that the prevalence of
      intracranial aneurysms is about 13% in ADPKD, and that MRA is useful in screening
      for occult intracranial aneurysms in patients with ADPKD.

PMID- 9567071
TI  - [Renal damage in a chronic active hepatitis C patient receiving interferon-alpha
      therapy].
AB  - A 68-year-old male patient with chronic active hepatitis C was treated with
      interferon-alpha (IFN-alpha) for a period of 5 months. The patient responded well
      to the IFN therapy showing substantial improvement in liver function and
      disappearance of HCV-RNA. However, one year after the treatment he was found to
      have developed proteinuria and showed a reduction in Ccr. Renal biopsy findings
      were as follows: Light microscopy showed diffuse expansion of mesangial cells
      with a focal/local increase in cellularity accompanied by capillary loop
      thickening. Splitting of the basement membrane was also present. An
      immunofluorescent study showed that IgA was localized predominantly in the
      peripheral capillary wall. Electron microscopy showed that there was mesangial
      cell interposition between the peripheral capillary wall and endothelial cells.
      Furthermore, endothelial cells were expanded and numerous platelets were seen in
      the capillary lumen. These findings were compatible with focal MPGN accompanied
      by activation of endothelial cells. These histological data suggest two clinical
      disease entities: late-onset renal damage induced by IFN-alpha alone, and HCV
      induced renal damage possibly modified by the direct effect of IFN-alpha on the
      endothelium. The present case suggests that IFN therapy for HCV may produce a
      particular type of renal damage, under the influence of either IFN or HCV
      infection, and/or both.

PMID- 9567072
TI  - [A case of glomerulonephritis with singular high titer of anticardiolipin
      antibody].
AB  - We report here a case of severe membranoproliferative glomerulonephritis with a
      singular high titer of anticardiolipin antibody (aCL). A 19-year-old Japanese
      female was admitted to Tsukuba Gakuen Hospital after complaining of general edema
      for 5 months. She had no past history of thrombosis, thrombocytopenia, or
      spontaneous abortion. Laboratory findings revealed that she had nephrotic
      syndrome and moderate renal dysfunction. Immunological test showed a high titer
      of aCL with a high-normal limit of antinuclear antibody, negativity for anti
      beta(2) glycoprotein I antibody and negativity for anti-DNA antibody. In the
      renal biopsy tissue, most glomeruli showed global sclerosis and the remaining
      glomeruli revealed membranoproliferative change with crescent formation. Steroid
      therapy with warfarin and dipyridamole was effective and her renal function
      improved gradually. This case lacked the typical symptoms of primary
      antiphospholipid syndrome and did not satisfy the criteria of SLE. In spite of
      these findings, the singular high titer of aCL with membranoproliferative
      glomerulonephritis characterized this case.

PMID- 9567073
TI  - [Age-related changes in static maximal inspiratory and expiratory pressures].
AB  - We evaluated 240 consecutive subjects (aged 20-91) without cardiopulmonary,
      endocrine or, neuromuscular disease consecutively regarding pulmonary function
      (TLC, VC, FEV1, RV) and static maximal inspiratory (PImax) and expiratory (PEmax)
      pressures. PImax and PEmax declined with advancing age. PImax correlated with
      grip strength, VC, FEV1, height, weight, and RV/TLC. PEmax also correlated with
      grip strength, TLC, VC, FEV1, height, and weight. Age, height, weight, and grip
      strength were entered stepwise into multiple linear regression models with PImax
      or PEmax as the dependent variable. Stepwise regression analysis revealed that
      grip strength was an independent predictor for both PImax and PEmax. However, age
      itself was not an independent predictor for PImax or PEmax. These results suggest
      that static maximal respiratory pressures decrease with aging, and that age
      dependent changes in respiratory muscle function may depend on other factors,
      including lung volume, skeletal muscle status, and body composition.

PMID- 9567074
TI  - [Effect of DNA topoisomerase I inhibitor on the transduction efficiency of an
      deno-associated virus vector in human airway epithelial cells].
AB  - We tested the effects of a DNA topoisomerase inhibitor (camptothecin; CPT) on the
      transduction efficiency of AAV vectors in cultured human airway epithelial cells.
      The cells were treated with CPT for 24 hours, then exposed to AAV-CMV-LacZ for 1
      hour at different multiplicities of infection (moi). Transduction efficiency of
      AAV vectors was assessed using X-gal staining as the percentage of LacZ
      expressing cells. The transduction efficiency was approximately 1.5 to 10 fold
      increased by treatment with CPT prior to AAV vector exposure. However, treatment
      with CPT after AAV vector infection did not enhance the transduction efficiency
      of the vectors. These results suggest that pre-treatment with CPT increases the
      transduction efficiency of AAV vectors, probably by nodulating cellular function.

PMID- 9567075
TI  - [Effect of dopamine receptor on hypoxic ventilatory response].
AB  - We studied the effect of intravenous administration of a dopamine (DA) agonist
      and antagonist on the hypoxic response of phrenic nerve activity in anesthetized,
      vagotomized and mechanically ventilated rabbits. The experiments were performed
      in both intact and carotid sinus denervated animals. In the intact animals,
      hypoxic challenge (FIO2 = 0.10) increased the amplitude of integrated phrenic
      nerve activity (iPNA) without any alteration in respiratory frequency. In the
      carotid sinus denervated animals, the hypoxia progressively depressed iPNA.
      Neither the DA antagonist, haloperidol (0.5mg/kg i.v.), nor the DA agonist,
      apomorphine (0.3mg/kg, i.v.) changed the iPNA during normoxia in either the
      intact or denervated group. Administration of haloperidol enhanced iPNA response
      to hypoxia in the intact group. Apomorphine decreased the hypoxic response to
      iPNA. Although apomorphine did not change the control hypoxic response to iPNA in
      the denervated group, haloperidol augmented hypoxic respiratory depression in the
      carotid sinus denervated group. Therefore, we concluded that the effect of DA on
      peripheral chemoreceptors inhibits the hypoxic ventilatory response, but
      stimulates the hypoxic ventilatory response in the central nervous system.

PMID- 9567076
TI  - [Clinico-pathological analysis of interstitial pneumonia associated with collagen
      vascular disease in patients with lung cancer].
AB  - We investigated interstitial pneumonia associated with collagen vascular disease
      (IP-CVD) in association with lung cancer. Seventy-three cases of IP-CVD were
      included in this study. Nine (12%) of the 73 cases were associated with lung
      cancer, one of which had double lung cancers. The histological types of the
      cancers were adenocarcinoma (5 cases), epidermoid carcinoma (2 cases), small cell
      carcinoma, large cell carcinoma and large cell neuroendocrine carcinoma (one case
      each). The lesions were located in the central or peripheral lung in 3 and 7 of
      the ten cancers, respectively. Of the seven cases diagnosed as having IP-CVD
      followed by lung cancer, five had stage I disease, and one each of the remaining
      two cases was in stage IIIA and stage IV. Six of the seven peripheral cancer
      lesions which were resected or autopsied could be analyzed with regard to the
      topographical relationship between the primary site and fibrotic lesions. Only
      three cancers were encased by or in close proximity to, honeycomb lung, although
      most of the lung cancers arose in relation to fibrotic lesions. Moreover, the
      acute exacerbation of IP-CVD after operation or chemotherapy without thoracic
      irradiation should be monitored carefully.

PMID- 9567077
TI  - [CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with
      pulmonary tuberculosis--comparison with healthy controls].
AB  - We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from
      healthy donors had similar effector functions (cytotoxicity and cytokine
      production) in response to mycobacterial antigens, despite differences in the
      antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis,
      this study was undertaken to compare T cell functions between patients with
      pulmonary tuberculosis with no complications and healthy controls. Both resting
      and activated CD4+ and gamma delta T cells from the patient group proliferated in
      response to live BCG at a significantly lower rate than those from the control
      group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both
      the CD4+ and gamma delta T cells from patients was significantly lower than those
      of controls. In contrast to IFN-gamma, significantly higher IL-10 production by
      both CD4+ and gamma delta T cells from patients was detected. The proliferative
      responses to BCG by CD4+ and gamma delta T cells from patients after
      antituberculous therapy were partially restored, but remained at lower levels
      compared with controls. These results suggest that not only a general
      deterioration in CD4+ and gamma delta T cells effector functions, but also
      suppressive factors (such as IL-10) might be responsible for the pathogenesis of
      pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma
      delta T cells in patients with tuberculosis is in part attributable to patient
      predisposition.

PMID- 9567078
TI  - [Estimation of respiratory muscle endurance using an inspiratory threshold
      loading device in patients with chronic pulmonary emphysema and in elderly
      subjects].
AB  - We studied respiratory muscle endurance with an inspiratory threshold loading
      (ITL) device using Martyn's method (2-min incremental loading test) in 9 patients
      with chronic pulmonary emphysema (CPE patients) and in 9 elderly subjects with no
      lung disease (NE subjects), and their endurance was compared with that of 9
      normal young subjects (NY subjects). In 11 cases (8 CPE patients and 3 NE
      subjects) a treadmill exercise test was performed and cardiopulmonary parameters
      obtained from the ITL and treadmill tests were compared. The maximum weight
      tolerated for 2 minutes (Wmax) and the mean peak inspiratory mouth
      pressure/maximum inspiratory mouth pressure ratio at the maximum load (Ppk/MIP at
      Max Load) were used as indices of respiratory muscle endurance. CPE patients had
      significantly decreased Wmax compared with those of NE and NY subjects. Wmax in
      all cases positively correlated with Ppk/MIP at Max Load, and endurance time of
      both the ITL and treadmill tests. During both tests, SaO2 significantly
      decreased, and heart rate and mean blood pressure significantly increased. There
      was less change in SaO2 and heart rate during the ITL test than during the
      treadmill test, and neither arrhythmias nor ST changes on ECG were observed
      during the ITL test. These results indicate that the ITL test can be easily and
      safely employed in CPE patients and elderly subjects to estimate respiratory
      muscle endurance.

PMID- 9567079
TI  - [A case of Sairei-to-induced pneumonitis diagnosed by lymphocyte stimulation test
      of bronchoalveolar lavage fluid].
AB  - A 51-year-old woman was admitted with fever, cough and dyspnea. She had been
      taking Sairei-to, a traditional Chinese medicine, for 2 months. On admission,
      chest X-ray revealed a ground-glass appearance in the lung fields bilaterally and
      serum LDH was elevated. A differential cell count of the bronchoalveolar lavage
      fluid (BALF) showed that lymphocytes were increased, with a decreased ratio of
      CD4/CD8 cells. A lymphocyte stimulation test (LST) for Sairei-to using the
      lymphocytes in BALF was a positive, although a test of peripheral blood was
      negative. Sairei-to-induced pneumonitis was diagnosed based on the clinical
      course, laboratory findings, BALF cell analysis and LST of BALF. Only 4 cases of
      pneumonitis due to Sairei-to have been reported. This case suggests that LST of
      BALF is useful for diagnosing drug-induced pneumonitis.

PMID- 9567080
TI  - [Nasopharyngeal myiasis during mechanical ventilation].
AB  - We report a case of myiasis caused by Phaenicia sericata during mechanical
      ventilation. An 86-year-old woman with bronchiectasis was admitted to our
      hospital with severe respiratory failure. Treatment with mechanical ventilation
      and sedatives was initiated. On the 10th day of hospitalization, about 20 white
      larvae were found in the patient's oral or nasal cavities. The larvae were
      removed and identified as Phaenicia sericata. No mucosal injury was found in the
      patient's oral or nasal cavity by endoscopic examination. The patient died of
      multiple organ failure caused by sepsis that had no association with myiasis.
      From the clinical course and the fly's life cycle, it is considered that the fly
      laid eggs in the patient's oral or nasal cavity while she was sedated during
      mechanical ventilation. Myiasis can occur even in a hospital.

PMID- 9567081
TI  - [A case of Goodpasture's syndrome with myeloperoxidase specific anti-neutrophil
      cytoplasmic autoantibody (MPO-ANCA) during chronic interstitial pneumonia].
AB  - A 55-year-old man was admitted to our hospital with of hemoptysis, progression of
      anemia and renal failure in February, 1996. Idiopathic interstitial pneumonia had
      been diagnosed and he had been followed at a regional hospital since 1988. On the
      third day after admission, he suffered from sudden and massive hemoptysis.
      Goodpasture's syndrome was diagnosed because anti-GBM antibody was detected in
      serum. A high titer of MPO-ANCA was also recognized simultaneously. Steroid pulse
      therapy, immunosuppressive therapy, and plasmapheresis were begun, but he died on
      the 28th hospital day because of severe hypoxemia and multi-organ failure.
      Histological examination after autopsy revealed crescentic glomerulonephritis
      with linear deposition of IgG in the glomerular capillary wall, and interstitial
      pneumonia accompanied by massive alveolar hemorrhage. It was suggested that in
      this patient, not only anti-GBM antibody but also circulating MPO-ANCA might have
      participated in the progression of the crescentic glomerulonephritis and alveolar
      hemorrhage observed in Goodpasture's syndrome.

PMID- 9567082
TI  - [Extracorporeal membrane oxygenation for acute respiratory failure induced by
      Legionella pneumoniae. (Case report)].
AB  - We report a case of severe legionella pneumonia with acute respiratory failure,
      successfully managed with veno-venous extracorporeal membrane oxygenation (VV
      ECMO). The patient presented with 4-day history of fever and cough. He was in
      critical condition, with exacerbated respiratory failure. Mechanical ventilation,
      volume replacement and antibiotic therapy were initiated. Despite increasing
      mechanical ventilatory support (FiO2 100%, TV 10 ml/kg, f 30/min, PEEP 5 cmH20),
      PaO2 fell below 40Torr and life sustaining measures were undertaken. VV-ECMO
      (flow 30 ml/kg/min) was commenced, and the patient responded well, with an
      elevation of PaO2. Erythromycin therapy was effective against the pneumonia. VV
      ECMO was maintained for 92 hours, mechanical ventilation was successfully
      discontinued 11 days after and the patient was discharged 82 days after cessation
      of ventilator support. Serum antibody examination proved legionella infection. VV
      ECMO may have a role in the management of patients with acute respiratory failure
      caused by bacterial pneumonia.

PMID- 9567083
TI  - [Sero-negative tsutsugamushi disease (scrub typhus) diagnosed by polymerase chain
      reaction].
AB  - We report a case of sero-negative tsutsugamushi disease diagnosed by polymerase
      chain reaction (PCR). A 54-year-old man who worked in Nagano prefecture presented
      with flu-like symptoms that did not respond to cephalosporin therapy. On
      admission to another hospital, chest roentgenography revealed abnormal shadows;
      liver dysfunction was also present. Despite therapy, the patient's condition
      gradually worsened and he was transferred to our intensive care unit. Erythema on
      all extremities and scabs on the right medial femoral region and the dorsum of
      the left foot suggested a diagnosis of tsutsugamushi disease. We administered
      minocycline and gave percutaneous cardiopulmonary support for adult respiratory
      distress syndrome. Despite all efforts, the patient died. Although serologic
      tests were not positive, Karp strains of R. tsutsugamuschi were identified on PCR
      amplification. Autopsy revealed evidence of acute hemorrhagic pancreatitis, which
      has not been reported previously in tsutsugamushi disease. We conclude that PCR
      techniques may be useful in confirming a diagnosis of early tsutsugamushi
      disease.

PMID- 9567084
TI  - [A case of acute eosinophilic pneumonia due to Sho-saiko-to].
AB  - A 16-year-boy who had taken a common over-the-counter cold remedy containing Sho
      saiko-to, presented with fever, severe cough, sputum and dyspena. Two days later,
      he was admitted because a negative density, pulmonary edema-like shadow was noted
      on chest X-ray. A diagnosis of drug-induced pneumonia was strongly suspected,
      because an arterial blood gas analysis showed severe hypoxemia and leukocytosis
      with eosinophilia, and the chest X-ray showed a diffuse negative density
      pulmonary edema like shadow bilaterally. The findings on microscopic examination
      of transbronchial lung biopsy specimens were compatible with eosinophilic
      pneumonia. The eosinophil percentage in the bronchoalveolar lavage fluid was
      high. The result of a lymphocyte-stimulation test was positive for Sho-saiko-to,
      and Sho-saiko-to-induced pneumonia was strongly suspected. The patient ceased
      taking the cold remedy, and prednisolone was given. The clinical symptoms, severe
      hypoxemia, and chest X-ray findings markedly improved. To the best of our
      knowledge, there have been no previous reports of acute eosinophilic pneumonia
      induced by Sho-saiko-to.

PMID- 9567085
TI  - [A case of amyloidosis of the tracheobronchial tree and inferior nasal concha].
AB  - A 50-year-old man resented at a local medical clinic with nasal obstruction. He
      was treated but did not improve. He then consulted our institution. Chest X-ray
      disclosed infiltrative shadows in the basal region of the left lung. A computed
      tomography scan of the lung showed marked thickening of the airway walls
      extending from the trachea to both bronchial trees and obstructive changes in the
      left lower lobe of the lung. On bronchoscopic examination the bronchial mucosa
      was reddened and edematous with a pinhole bronchial obstruction in one region.
      Congo red staining of biopsy samples taken from the bronchial mucosa showed
      deposition of an amorphous substance. Tracheobronchial amyloidosis was diagnosed.
      The amyloid material was resistant to potassium permanganate and tested positive
      for lambda-chain of L immunoglobulin. Otorrhinolaryngological examination
      disclosed a tumor in the inferior nasal concha as the cause of his nasal
      obstruction. The nasal tumor was resected and AL lambda-type amyloidosis was
      diagnosed pathologically. Tracheobronchial and inferior nasal concha amyloidosis
      is an extremely rare pathological condition. The patient was followed for one
      year and remain asymptomatic without treatment.

PMID- 9567086
TI  - [A case of interstitial pneumonia induced by intravesical administration of
      bacillus Calmette-Guerin (BCG)].
AB  - A 61-year-old man with superficial bladder cancer, which was detected after he
      complained of hematuria, was treated three times with intravesical BCG
      administration. Since liver dysfunction was detected thereafter, he was admitted
      to our hospital. Three days after admission, he complained of dyspnea on exertion
      associated with severe hypoxemia, as well as abnormal findings on chest X-ray,
      i.e. extensive bilateral lung densities. We performed bronchoscopic examination
      and obtained bronchoalveolar lavage fluid (BALF) and lung biopsy specimens
      (TBLB). In the BALF, a marked increase in the total cell number, particularly
      lymphocytes with a high CD4/CD8 ratio was noted. TBLB specimens revealed the
      lesions to be numerous non-caseating granulomas. We failed to obtain definite
      evidence of BCG in the sputum, urine, blood, and BALF. Instead, we found that a
      lymphocyte stimulation test for BCG (DLST) was strongly positive. Based on these
      findings, severe interstitial pneumonia probably induced by hypersensitivity
      against BCG, was diagnosed. Anti-tuberculous agents, and steroid-pulse therapy
      followed by oral administration of relatively low dose of steroid ameliorated the
      abnormal conditions, including chest X-ray film findings and hypoxemia. The
      population of lymphocytes and CD4/CD8 ratio in the BALF were reduced as well.
      Serious interstitial pneumonia was induced by the intravesical administration of
      BCG, which resulted in transitional changes in the BALF cell component.

PMID- 9567087
TI  - [A case of multifocal Langerhans cell granulomatosis: a BAL follow up study].
AB  - Langerhans cell granulomatosis, once called histiocytosis X, is a rare disease. A
      case of multifocal Langerhans cell granulomatosis in the bone, lymph nodes, skin
      and lungs of an 18-year-old man is described. Head CT and MRI showed a soft
      tissue mass of the left temporal bone. Lymph node and skin biopsies substantiated
      a diagnosis of Langerhans cell granulomatosis. A High resolution CT scan of the
      lung revealed a small cystic lesion, and bronchoalveolar lavage (BAL) showed an
      increased number of S-100 positive cells. Steroid therapy resulted in complete
      resolution, and no S-100 positive cells were obtained in the follow-up BAL study.

PMID- 9567088
TI  - [A case of non-specific interstitial pneumonia associated with psoriasis vulgaris
      and polymyalgia rheumatica].
AB  - We describe the first case, to the best of our knowledge, of non-specific
      interstitial pneumonia associated with psoriasis vulgaris and polymyalgia
      rheumatica (PMR). A 50-year-old woman was admitted with a dry cough and a
      bilateral basilar reticulonodular shadows on chest X-ray. Bronchoalveolar lavage
      fluid analysis revealed lymphocytosis and a decreased CD4/CD8 ratio. A
      thoracoscopic lung biopsy specimen showed evidence of non-specific interstitial
      pneumonia. During her clinical course, she began suffering from psoriasis
      vulgaris and polymyalgia rheumatica. Corticosteroid therapy had no effect, but
      maintained a stable condition during a follow-up period of 4 years.

PMID- 9567089
TI  - [A case of primary acute pulmonary cavitation in sarcoidosis complicated by
      multiple nodular lesions in the central nervous system].
AB  - A 20-year-old man visited our hospital complaining of headache and a dry cough.
      Chest X-ray and chest CT showed bilateral hilar and mediastinal lymphadenopathy,
      multiple cavitations with thin, smooth walls, and diffuse granular shadows. A
      transbronchial biopsy specimen revealed sarcoid granuloma. Primary acute
      pulmonary cavitation of sarcoidosis was diagnosed, since there was no evidence of
      infection, emphysematous change, fibrotic or cystic bronchiectatic change on
      chest X-ray. EEG, contrast enhancement of brain CT scans and MRI were performed
      because the patient complained of headache. EEG showed a high voltage paroxysmal
      slow wave and giant build-up, whereas brain CT showed no abnormalities. T1
      weighted MRI with gadolinium enhancement showed multiple high intensity nodules
      in the convexity, brain stem, and spinal cord. Corticosteroid therapy (60 mg/day)
      was started. After 1 week of treatment, the headache ceased. After 2 weeks of
      treatment, both the cavities in the lung field's and the nodules in the central
      nervous system disappeared. Therefore, the dose of corticosteroids was gradually
      reduced to a maintenance dose of 5 mg/day, and no relapse was noted. We report a
      very rare case of primary acute pulmonary cavitation in sarcoidosis complicated
      by multiple nodular lesions in the central nervous system.

PMID- 9567090
TI  - [Clinical investigation of three cases of pulmonary eosinophilic granuloma].
AB  - Patient 1: An 18-year-old woman was admitted to our hospital with pneumothorax.
      She had no history of smoking. Chest CT showed multiple cysts, and pulmonary
      eosinophilic granuloma was diagnosed by open lung biopsy. She recovered without
      therapy 3 months later and a chest CT taken at that time was normal. She began
      smoking, 3 years later, and bore two children. She is without recurrence after 8
      years. Patient 2: A 23-year-old man was admitted to our hospital with
      pneumothorax. He had a smoking history (index = 180). Chest CT showed multiple
      cysts, and pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. He
      stopped smoking and recovered without therapy one month later, and subsequently,
      his CT findings returned to normal. Two years later, he began smoking again, but
      has no relapse. Patient 3: A 21-year-old man was admitted to our hospital with
      pneumothorax. He had no history of smoking. A chest CT showed multiple cysts, and
      pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. Diabetes
      insipidus was subsequently noted. Dyspnea persisted, and he recovered 4 months
      later after steroid treatment. He was without relapse 2 years later but the
      multiple cysts remained. We report three cases of pulmonary eosinophilic
      granuloma, and discuss their pertinent clinical features.

PMID- 9567091
TI  - [Pulmonary thromboembolism associated with antiphospholipid syndrome in
      scleroderma].
AB  - A 51-year-old woman was referred to our hospital with dyspnea. Chest
      roentgenogram on admission showed dilation of the pulmonary arteries and
      hyperlucency in the lung fields. An ultrasonic cardiographic examination showed
      that the right atrium and ventricle were dilated. Pulmonary thromboembolism due
      to left popliteal vein thrombosis was diagnosed by perfusion scintigram of the
      lung, which showed multiple wedge-shaped defects, and by digital subtraction
      angiogram, which showed a filing defect in the left popliteal vein.
      Antiphospholipid syndrome was diagnosed after IgG anticardiolipin antibody was
      defected. Scleroderma was subsequently diagnosed because the patient exhibited
      Raynaud's phenomenon and proximal scleroderma. Although closely associated with
      lupus erythematosus and other lupus variants, antiphospholipid syndrome has not
      been recognized as a common complication of scleroderma. This is the first report
      of a patient with pulmonary thromboembolism associated with antiphospholipid
      syndrome and scleroderma.

PMID- 9567092
TI  - [A case of allergic bronchopulmonary aspergillosis caused by Aspergillus
      terreus].
AB  - A 66-year-old woman was admitted to our hospital with a cough, wheezing, and
      expectoration. Chest X-ray and CT scanning revealed atelectasis and infiltration
      of the middle lobe, but no central bronchiectatic change. The patient had
      eosinophilic infiltration elevated serum IgE, RAST against Aspergillus )(A.)
      fumigatus, a positive immediate skin reaction, and a positive test for antibodies
      against A. funmigatus. Bronchoscopy demonstrated mucoid impaction that plugged
      the middle lobe bronchus. The mucoid plug contained A. terreus and numerous
      eosinophils. Because the level of the precipitating antibody for counter
      immunoelectrophoresis against A. terreus was higher than that at A. fumigatus,
      allergic bronchopulmonary aspergillus caused be A. terreus was diagnosed. Oral
      and inhalation therapy of corticosteroids ameliorated the symptoms and abnormal
      laboratory findings.

PMID- 9567093
TI  - [A resected case of intralobar pulmonary sequestration with increased serum tumor
      markers, CA19-9, CA125 and NCC-ST-439].
AB  - A 39-year old female was found to have intralobar pulmonary sequestration with a
      high serum level of the tumor markers, CA19-9, CA125 and NCC-ST-439. The lesion
      was located in the left S10 and an aberrant artery from the aorta was noted.
      After partial resection of the left lower lobe, serum levels of the tumor markers
      (CA19-9 2418U/ml, CA125 50.3U/ml, NCC-ST-439 13.0U/ml) gradually returned to
      normal. The half-life of serum CA19-9 was about 7 days. Immunohistochemical
      analysis revealed that CA19-9 was being produced in the bronchial epithelium of
      the sequestered lung. Increased serum levels of CA19-9 may be helpful in
      diagnosing pulmonary sequestration.

PMID- 9567095
TI  - The evolution of the dental practice: the functionally designed office.

PMID- 9567094
TI  - [A case of expanding pulmonary aspergilloma].
AB  - A 60-year-old female had old pulmonary tuberculosis. Chest radiographs taken in
      1980 revealed a small cavitary lesion due to old lung tuberculosis in the right
      upper lung fields. Chest radiographs taken in 1984 revealed a fungus ball in the
      cavity and the adjacent pleura was thickened. Chest radiographs taken in 1994,
      revealed that the margin of the fungus ball had become ill-defined, and
      infiltrative shadows surrounded the cavity. A test for aspergillus antigen was
      positive and toxicolor test was elevated in serum. Chest radiographs taken in
      1996 revealed that the fungus ball had enlarged substantially. We consider this
      case to be a semi-invasive pulmonary aspergillosis which spread by direct
      invasion from an aspergilloma to the surrounding cavitary wall.

PMID- 9567097
TI  - Contemporary periodontics and a vision for the future: diagnostics and monitoring
      the treated case.

PMID- 9567096
TI  - Buying high technology on a shoestring.

PMID- 9567098
TI  - Beyond technique: The need for educated fee-setting.

PMID- 9567100
TI  - A potpourri of overdenture stud attachment systems.

PMID- 9567099
TI  - Progressive bone loading.

PMID- 9567101
TI  - Simplified method for direct resin composite veneers placement.

PMID- 9567102
TI  - Managed care in dentistry. Interview by Phillip Bonner.

PMID- 9567103
TI  - Update on TB, waterlines, ventilation and ergonomics.
AB  - As the study of diseases changes, the focus must remain the same: To provide the
      highest quality of care in the safest healthcare environment. It is absolutely
      necessary to continue a relentless pursuit to keep current with new emerging
      diseases and adapt solutions that eliminate waterline contamination, support
      ventilation standards, and ergonomic practices as they apply to dentistry. It's
      not enough to eliminate the symptom, we must prevent the cause. The standard of
      care must be constantly challenged with an awareness and acceptance to improve
      modes of operation as they become necessary. This commitment, in and of itself,
      allows us to take a proactive approach in ensuring not only our own futures, but
      also those of whom we serve.

PMID- 9567104
TI  - Gingivitis: to treat or not to treat?

PMID- 9567105
TI  - Following up on collection calls.

PMID- 9567106
TI  - Should dentists use medical codes for third-party reimbursement?. Interview by
      Phillip Bonner.

PMID- 9567107
TI  - A vision for the future: diagnostics and recognition.

PMID- 9567108
TI  - A conservative alternative to traditional fixed partial dentures.

PMID- 9567109
TI  - Protocol for predictable porcelain veneers: case selection, preparation,
      temporization, cementation and finishing.

PMID- 9567110
TI  - Using opalescent light filters in restoring teeth.

PMID- 9567111
TI  - Conquering space, Part I.

PMID- 9567112
TI  - Restoring endodontically treated teeth.

PMID- 9567113
TI  - Dental iatrogenesis, Part 2.
AB  - To substantiate biocompatibility of dental materials and techniques, and thereby
      reduce iatrogenesis, tests for pulp and dentinal responses have been developed.
      These have shown that high-speed tooth cutting techniques are superior to low
      speed techniques even when both incorporate air-water coolant sprays; pressure
      when placing restorative materials intensifies pulp responses induced by the
      cutting procedure, and that chemically self-cured resin composites requiring the
      application of a matrix to enhance adaptation intensify pulp response as compared
      to visible light-cured equivalents applied incrementally, fully cured throughout,
      and not requiring the pressure of a matrix. Most cements are irritating to the
      pulp when used as luting agents and when used less than 0.5 mm from it.
      Conditioning agents using weak acids for short periods induce little irritation
      while bonding agents appear to be beneficial by providing protection from
      subsequently placed restorative material. Clinicians should make every effort to
      minimize the development of pulp responses and reduce iatrogenic efforts.

PMID- 9567115
TI  - Tooth whitening: an idea whose time has come.

PMID- 9567114
TI  - Endodontics in the fourth dimension: dentin meets the silicon chip in new
      millennium.

PMID- 9567116
TI  - Collections and the practice interview: the next line of attack.

PMID- 9567117
TI  - Peace of mind, Part 1: how much is enough?

PMID- 9567118
TI  - Author reacts to letters.

PMID- 9567119
TI  - AIDS letters generate response.

PMID- 9567120
TI  - Survey reveals physician reluctance to treat HIV babies for 'expensive'
      conditions.

PMID- 9567121
TI  - HIV/AIDS and healthcare workers report update.

PMID- 9567122
TI  - Dealing proactively with disaster. Interview by Cheryl Farr.

PMID- 9567123
TI  - Update on adhesive dentistry: an interview with Dr. Harald Heymann. Interview by
      Phillip Bonner.

PMID- 9567124
TI  - Sub-opaquing tetracycline stains to attain aesthetic porcelain veneers.

PMID- 9567125
TI  - Bioaesthetics: the study of beauty in life.

PMID- 9567126
TI  - Full team approach for provisional stabilization of edentulous patients.

PMID- 9567127
TI  - The continuous wave of obturation technique: 'centered' condensation of warm
      gutta percha in 12 seconds.

PMID- 9567128
TI  - Multidisciplinary approach to achieving aesthetics and function: a case report
      using adhesive dentistry.

PMID- 9567129
TI  - Syncope: treating fainting in the dental office.

PMID- 9567131
TI  - Lease or purchase?

PMID- 9567130
TI  - Aesthetic restorations for congenitally missing teeth--a case study.

PMID- 9567132
TI  - The ergo factor: the most common equipment & design flaws & how to avoid them!

PMID- 9567133
TI  - Managing time for greater effectiveness: designing doctor's ideal day.

PMID- 9567134
TI  - AIDS debate built on hysteria.

PMID- 9567135
TI  - Update on dentistry: an interview with Dr. Gordon Christensen. Interview by
      Phillip Bonner.

PMID- 9567136
TI  - The road ahead. Interview by Cheryl Farr.

PMID- 9567137
TI  - The art of endodontics: files of greater taper.

PMID- 9567138
TI  - New directions in periodontics: the future is now.

PMID- 9567139
TI  - Above the drill: a perspective on cosmetic dentistry.

PMID- 9567140
TI  - The art of indirect composites, Part 1.

PMID- 9567142
TI  - Maxillary anterior porcelain crowns: ingredients for optimum aesthetics, Part
      III.

PMID- 9567143
TI  - Benefit-driven treatment planning, Part II: the implant-retained bar overdenture.

PMID- 9567141
TI  - An aesthetic alternative to PFM. Porcelain fused to metal.

PMID- 9567144
TI  - Bleaching for veneering.

PMID- 9567145
TI  - Orthodontic repositioning of a severely impacted maxillary canine.

PMID- 9567146
TI  - Instrument circulation, Part 2.

PMID- 9567147
TI  - Scheduling to make the most of the practice day.

PMID- 9567148
TI  - How to introduce and retain associate dentists.

PMID- 9567149
TI  - [A Biotop is dying--or dealing with unloved child. The future of pain therapy in
      field of anesthesiology].

PMID- 9567150
TI  - [Stereoisomers in anesthesia. Theoretical basis and clinical significance].
AB  - All optically active molecules have at least one asymmetric atom in common which
      is attached to four ligands, that can have different three dimensional positions.
      Therefore it can be concluded that the resulting isomers are chemically identical
      in all respects except for the direction with which they rotate plane-polarized
      light. When the isomer and its corresponding enantiomer are present in equal
      proportions, they are called racemic mixture, a mixture that does not rotate
      polarized light, since the optical activities of the two isomers cancel each
      other. Although the isomers are chemically identical other optically active
      molecules can interact with these isomers in a geometrically specific way termed
      stereoselectivity. The human body comprises a chiral environment due to optically
      active proteins; thus it is not surprising that enantiomeric drugs exhibit
      different pharmacological properties, when used as pure optical isomers. Till
      today most modern anaesthetics have been optical isomers, which are mainly used
      as racemic mixture (1:1 mixture). For financial reasons pure isomers were only
      used for research purposes, but nowadays the wide clinical use of pure isomers is
      financially feasible due to new production techniques. The terms eutomer and
      distomer were chosen to indicate the more or less potent form of the drug. The
      clinical use of pure isomers is only of advisable, if there are significant
      differences between eutomer and distomer in desired or side effects. Among the
      modern anaesthetics ketamine, isoflurane, bupivacaine and atracurium exhibit an
      asymmetric carbon. For most drugs the separation in pure isomers will reduce side
      effects. For volatile anaesthetics this question is still unanswered, since
      experimental and clinical results are inconsistent so far.

PMID- 9567151
TI  - [Recovery time after (S)-ketamine or ketamine racemate. Recovery time after short
      anesthesia in volunteers].
AB  - The anaesthetic potency of the (S)-ketamine isomer is approximately double that
      of racemic ketamine. The aim of this study was to compare the recovery of
      cerebral function after a bolus of 1.3 mg/kg racemic ketamine or 0.65 mg/kg (S)
      ketamine followed by continuous application of 4 or 2 mg/kg x h over 15 minutes.
      METHODS: With their informed consent and approval of the local ethics committee
      12 healthy volunteers were enrolled in a double-blind, cross-over study. All
      drugs were dissolved in identical volumes. On three dates with an interval of one
      week at least ketamine/NaCl, (S)-ketamine/physostigmine or (S)-ketamine/NaCl was
      administered (table 1). The sequence was randomized. In addition, the unspecific
      antagonistic potential of the centrally acting, cholinergic agonist physostigmine
      (0.012 mg/kg) after (S)-ketamine was tested against saline-placebo.
      Neuropsychological tests (tests 3-5 of the syndrome-short-test [Erzigkeit, see
      references]) were used to quantify cerebral function before and at 45, 75, 105,
      135, 165 and 195 min after anaesthesia. All data are mean values and standard
      deviation. Comparisons over time and between drugs were carried out using two
      dimensional analysis of variance (ANOVA). Wilcoxon-tests were used post-hoc. p <
      0.05 was considered significant. RESULTS: After (S)-ketamine the subjects were
      able to carry out the tasks more rapidly than after racemic ketamine (p < 0.05).
      Mean time to reach preoperative test performance +10% was 117.5 min for (S)
      ketamine/physostigmine, 121.3 min for (S)-ketamine/NaCl and 141.6 min for racemic
      ketamine (p < 0.05 between (S)-ketamine and racemic ketamine). No differences
      were found between physostigmine and placebo. The incidence of side effects
      (mainly nausea, vomiting) was not different. DISCUSSION: (S)-ketamine offers a
      shorter recovery time after short anaesthesia compared to racemic ketamine. The
      investigated dose of physostigmine was probably too low to produce antagonism of
      (S)-ketamine. An increased dosage of physostigmine has yet to be studied, but is
      likely to cause a higher rate of side effects such as nausea, vomiting,
      bradycardia and possibly even tonic-clonic seizures.

PMID- 9567152
TI  - [Acute kidney failure. Non-invasive diagnosis of acute kidney failure in
      operative intensive care patients].
AB  - Acute renal failure is a common and severe complication in ICU. Renal laboratory
      examinations like creatinine and urea are late signs of renal dysfunction: Most
      of the functional abilities are reduced and there is no time for therapeutical
      interventions. The aim of this study was to find some earlier sensitive
      parameters of renal dysfunction and the order of appearance, the cause of acute
      renal failure and the value of the measured parameters. METHODS: After agreement
      of the local ethic committee, 21 patients of the ICU were investigated. They were
      divided into two groups: 1st (n = 14) with no signs of renal dysfunction and were
      regarded as control group and 2nd (n = 7) were examined until the beginning of
      acute renal failure. For five days the glomerular filtration rate, proteinuria
      (immunoglobulin G, Tamm-Horsfall protein, alpha-1- and beta-2 microglobulin,
      lysozyme), the brush border enzymes angiotensinase A and the lysosomal enzyme N
      acetyl-beta-d-glucosaminidase were daily measured and compared with clinical
      standards like the excretion of albumin, the clearances of creatinine and urea
      and the fractional excretion of sodium. RESULTS: Both groups were comparable with
      respect to drug therapy, APACHE-II-score (with the exception of the last day
      before ARF), and infusion therapy. There were differences in tubular functions
      between the 2 groups. Patients developing renal insufficiency showed an increased
      excretion of alpha-1-microglobulin, and decreased excretions of Tamm-Horsfall
      protein, angiotensinase A as well as a low renal blood flow. Significant
      differences were also detectable in glomerular functions (glomerular filtration
      rate), albumin, and immunoglobulin G. DISCUSSION: Only a short time interval (1
      to 2 days) between tubular and glomerular damage were detectable in patients with
      renal insufficiency. Renal failure must be due to circulatory problems because of
      the nearly simultaneous increase of tubular and glomerular parameters after RPF
      decreased. The parameters alpha 1-microglobulin, angiotensinase A and Tamm
      Horsfall-protein gave early indications for the acute renal failure. They showed
      satisfactory sensitivity and specificity, but the positive predictive value was
      poor.

PMID- 9567153
TI  - [Plasma concentrations of bupivacaine for continuous peridural anesthesia in
      children].
AB  - Epidural anaesthesia is extremely useful in providing postoperative analgesia for
      children after surgery of the lower body. Although results on early
      pharmacokinetics in children have previously been reported, no data are available
      on the long-term effects of epidural anaesthesia. The aim of this investigation
      was the assessment of plasma bupivacaine levels in children with continuous
      epidural anaesthesia in the postoperative period. A catheter with an outer
      diameter of 0.63 mm was inserted through a 19G Tuohy cannula into the epidural
      space. A maximum dose of 0.4 mg/kg/h bupivacaine was administered for continuous
      epidural infusion. Careful monitoring was performed to detect early signs of
      local anaesthetic intoxication. Two milliliters of blood were obtained in each
      patient per day and nepholometric serum measurement were performed to determine
      alpha 1-acid glycoprotein and albumin levels. Bupivacaine plasma concentrations
      were assessed according to the method described by Sattler et al. [25]. Ten
      children were included in the investigation. The measured albumin and alpha 1
      acid glycoprotein concentrations were within the range described by other
      investigators. At the onset of pain therapy maximum levels of 0.5 microgram/ml
      were recorded after a loading dose of bupivacaine and levels of up to 2.2
      micrograms/ml were achieved following continuous infusion. There were no
      neurologic complications or signs of local anesthetic intoxication. In conclusion
      our results show that a dose of up to 0.4 mg/kg/h bupivacaine during continuous
      epidural infusion is not associated with toxic complications. Careful monitoring
      of the children by experienced staff is mandatory.

PMID- 9567155
TI  - [Transpulmonary indicator methods in intensive medicine].
AB  - The management of critically ill patients often requires an advanced hemodynamic
      monitoring. Beside pulmonary artery catheter (PAC) and transesophageal
      echocardiography (TEE) the transpulmonary indicator dilution technique (TPID)
      with arterial registration of the indicator dilution curves is a possible
      approach to get additional hemodynamic information. Being less invasive,
      measurements of cardiac output by transpulmonary thermodilution are as reliable
      as the thermodilution using a PAC. Transpulmonary thermodilution can be used even
      in small children. In addition, intrathoracic blood volume (ITBV) and
      extravascular lung water (EVLW) can be estimated. ITBV seems to be a better
      surrogate of cardiac filling than central venous pressure and pulmonary capillary
      wedge pressure. EVLW can be of special value in the fluid-management of patients
      with systemic inflammatory response syndrome or acute respiratory failure. By
      using the dye indocyanine green (ICG) as a second indicator TPID can be performed
      as transpulmonary double indicator dilution technique. The resulting
      thermodilution and dye curves are measured with a combined fiberoptic-thermistor
      catheter. This allows the more accurate measurement of ITBV and EVLW and in
      addition the assessment of total circulating blood volume and ICG-clearance. ICG
      clearance serves clinically as a rapidly reacting indirect measure of liver
      function. As with the other methods of advanced hemodynamic monitoring the data
      available at present do not show a positive effect on the incidence of organ
      failure and mortality by monitoring critically ill patients with TPID. Before
      applying an advanced hemodynamic monitoring it should be asked critically which
      parameter is needed for the therapy-management of the individual patient. Based
      on this a differentiated monitoring decision has to be made.

PMID- 9567154
TI  - [SHFJV. Jet-adapter for application of superimposed high-frequency jet
      ventilation (SHFJV) via a tube in intensive care: a new technique].
AB  - Despite advances and technical developments in the area of intensive care
      medicine it has not been possible to lower the mortality of patients with
      pulmonary insufficiency. Therefore, alternative ventilation strategies have been
      developed and applied. One of these ventilation techniques is superimposed high
      frequency jet ventilation (SHFJV). For optimal application of SHFJV we designed a
      special jet-adapter. METHODS: This jet-adapter made of plastic consists of a T
      piece and four central, small-bore cannulas and can be connected to any
      commercially available endotracheal tube. Therefore, it does not require
      reintubation with an endotracheal jet tube when beginning SHFJV. The simultaneous
      high-frequency and low-frequency jet ventilation is performed over two jet
      nozzles that have been designed according to optimal flow dynamic measurements.
      Two further cannulas are used for continuous airway pressure monitoring and
      humidification of the applied gases. A pre-warmed and humidified bias flow with
      exactly defined oxygen concentration is led through the cross-part of the T-piece
      for gas entrainment. Additionally, the cross-part contains a port that can be
      opened for endotracheal suctioning or bronchoscopy and makes disconnection of the
      jet adapter from the endotracheal tube for either purpose unnecessary.
      CONCLUSION: The jet adapter can be used: (1) to apply SHFJV; (2) to measure
      airway pressures continuously; (3) to humidify and warm inspired gases; (4) to
      administer medications or add nitrous oxide by the inspiratory route, enabling
      combination with new therapeutic possibilities in the management of patients with
      severe ARDS.

PMID- 9567156
TI  - [Propofol for anesthesia and short-term sedation. The final word on use in
      children under three years].
AB  - Since its introduction in clinical use more than ten years ago, propofol is well
      appreciated for sedation and supplemental hypnosis in anaesthesia. However the
      substance is approved only for anaesthesia in children elder than three years. As
      can be substantiated by many data reported in literature, there are no
      pharmacokinetic or pharmacodynamic reasons whatsoever to withhold propofol from
      the younger children; this applies both to the use as a narcotic supplement and
      as a short term hypnotic for diagnostic and therapeutic interventions.

PMID- 9567157
TI  - [Patient-controlled analgesia. PCA in a three year old child after traumatic
      amputation].
AB  - We report the case of a 3-year-old boy, who received long-term parent-controlled
      analgesia after traumatic amputation of one leg. He underwent surgery 17 times
      for a period of 25 days. Parent-controlled analgesia was started four days after
      admission because analgesia with non-opioid analgetics (acetaminophen) proved to
      be insufficient. The pump was set to a bolus-dose of 23 micrograms kg-1
      piritramide (dipidolor) and a lockout interval of 10 minutes. Permitted maximum
      cumulative dose in four hours was 5 mg piritramide. There was no continuous
      infusion of opioid. PCA and possible adverse effects were explained to the
      mother. A monitoring regimen was used to assess efficacy (pain intensity
      estimated by the mother), adverse effects (sedation score, occurrence of nausea
      and vomiting) and piritramide consumption. For fear of side effects opioid
      administration was insufficient in the beginning. After three days the mother
      used the PCA effectively and no additional analgesic medication was required.
      Nausea or other side effects were not observed. After seven days opioid
      consumption nearly doubled. Apart from tolerance, this might have resulted from
      the mother's caution in the first days. After 17 days the PCA was discontinued.
      Oral analgetics (tramadol) controlled the pain adequately. Management of
      postoperative pain in children is difficult and too often insufficient. PCA is a
      safe and effective method of providing postoperative pain relief. Feasibility was
      shown in adolescents and, more recently, in children aged five years and over.
      Only few reports are available describing long term use of PCA in children
      younger than five years. Our case suggests that PCA may also be used effectively
      and safely in children younger than five years, if experienced staff, a
      monitoring regimen and cooperative and well instructed parents are available.

PMID- 9567158
TI  - [Prehospital thrombolytic therapy in acute myocardial infarction. Anaesthesist
      (1997) 46:829-839].

PMID- 9567159
TI  - [Nitrous oxide. Trends and current importance].

PMID- 9567160
TI  - [Blood transfusion and blood coagulation in the perioperative phase. Graz,
      December 12-13, 1997].

PMID- 9567161
TI  - [Diseases of acid-base imbalance].

PMID- 9567162
TI  - [Anesthesia risks with anabolic steroids].

PMID- 9567163
TI  - Relationship between sperm cell ubiquinone and seminal parameters in subjects
      with and without varicocele.
AB  - In a previous paper it was demonstrated that Coenzyme Q10, a lipidic molecule
      with important antioxidant properties, is present at remarkable levels in human
      seminal fluid, and shows a direct correlation with seminal parameters (sperm
      count and motility). In patients with varicocele, on the contrary, correlation
      with sperm motility was lacking and a higher proportion of Coenzyme Q10 was found
      in seminal plasma. In the present study, the levels of Coenzyme Q10 in the cell
      pellet of spermatozoa, obtained after centrifugation of semen, were evaluated. In
      nonvaricocele subjects it was observed that a higher concentration of Coenzyme
      Q10 (expressed as ng of the molecule per million of cells) was present in the
      spermatozoa of oligospermic and asthenospermic patients (sperm count < 20 x 10(6)
      spermatozoa ml-1, sperm motility < 40%). This relationship was not observed in
      varicocele subjects, who also showed slightly lower intracellular absolute values
      of the conenzyme. Since Coenzyme Q10 is an antioxidant molecule involved in the
      defence of the cell from free radical damage, higher intracellular concentrations
      may represent a mechanism of protection of the spermatozoa. In varicocele
      patients, this mechanism could be deficient, leading to higher sensitivity to
      oxidative damage.

PMID- 9567164
TI  - Erectile dysfunction following treatments of benign prostatic hyperplasia: a
      prospective study.
AB  - The effects of open prostatectomy, transurethral resection, transurethral
      vaporization, doxazosin and finasteride on sexual functions of men were
      investigated in a total of 305 patients with benign prostatic hyperplasia. The
      sexual functions of the patients were assessed with a questionnaire before
      treatment and 3 and 6 months after the treatment. A total of 212 (70%) patients
      were judged to be potent before the treatment. At 3 months, open prostatectomy
      and transurethral resection caused erectile dysfunction in 2 of 40 (5%) and 5 of
      89 (6%) potent patients, respectively. At 6 months, one of the patients from the
      former and 2 of the patients from the latter groups who developed erectile
      dysfunction at 3 months stated improvement. Transurethral vaporization caused
      loss of erectile functions in 4 of 14 potent patients (29%) at the 3-month follow
      up and, one of these patients recovered erectile functions at 6 months. Only one
      of the 33 patients (3%) using doxazosin stated that he lost his erectile
      functions both at 3 months and 6 months. At 3 months follow-up, finasteride
      caused loss of erectile functions in 8 of 36 potent patients (22%). Four of these
      patients underwent surgery (transurethral resection) after 3 months of
      finasteride use. At the 6-month follow-up, 4 more patients suffered from loss of
      erectile functions. We suggest that finasteride and transurethral vaporization
      have the greatest potential of impairing the sexual functions among the treatment
      options investigated in this study and that they must be carefully offered to the
      potent patients.

PMID- 9567165
TI  - Prevalence of human papilloma virus in men attending the infertility clinic.
AB  - Subclinical human papilloma virus is a potential carcinogen in the male and
      female genital tract. The sexually active male infertility population represents
      a high risk group for harbouring this disease. To determine the prevalence of
      subclinical human papillomavirus in this group, penoscopy was done on 96 male
      patients visiting the infertility clinic. The feasibility of routine penoscopy as
      part of the infertility work-up was also investigated. Of the 96 patients 20 had
      aceto-white lesions on their penises with penoscopy. Thirteen patients (13.5%),
      12 proven by biopsy of the aceto-white lesions, and one proven by fluid in situ
      hybridization on superficial epithelial cells of the distal urethra, were
      positive for human papillomavirus. Two of the 12 biopsy-positive cases were also
      proven positive by fluid in situ hybridization. It was concluded that human
      papillomavirus had a high prevalence amongst asymptomatic male patients attending
      the infertility clinic and that penoscopy should be included as routine
      investigation in the work-up of the male infertility patient.

PMID- 9567166
TI  - Estimation of sperm morphology using a new CASA system.
AB  - The rate of morphologically normal and abnormal spermatozoa plays a role in the
      prediction of male fertility and in the description of the integrity of
      spermatogenesis. It is thus important to estimate sperm morphology with
      reproducible results. For this purpose, several systems using computer-assisted
      image analysis were developed, similar to those used for the determination of
      sperm motility, which are known as CASA-systems. We tested an advanced CASA
      system using a neuronal network, which could be trained for the determination of
      classes of morphology defined by the WHO group. For the first time, this system
      also provided the automatic determination of midpieces and sperm tails. The
      system revealed no significant differences of the percentage of normal forms when
      compared to the direct microscopical estimation. However, nearly all the classes
      of pathological sperm heads were estimated by the two methods as being
      significantly different. Concerning midpieces, the neuronal net was unable to
      classify the normal forms correctly. The estimation of normal sperm tails by the
      two methods led to a sufficient correlation of values. Other classes of sperm
      tails, like curled or kinked tails, were not recognized by the software. The
      investigation time with the CASA system was twice as long as with the direct
      microscopical evaluation. Since functional characteristics of spermatozoa cannot
      be read from morphological parameters, it would be of use to measure the
      functional parameters directly. The main advantages of a CASA-system for sperm
      morphometry concerns laboratory quality controls.

PMID- 9567167
TI  - Association between sperm cell chromatin condensation, morphology based on strict
      criteria, and fertilization, cleavage and pregnancy rates in an IVF program.
AB  - In this study, a total of 95 ejaculates from infertile patients were investigated
      morphologically according to Kruger's strict criteria and 78 of the 95 ejaculates
      were stained for chromatin condensation with acidic aniline blue. Patients were
      divided into two groups based on the percentage of morphologically normal
      spermatozoa as follows: Men with normal sperm morphology < 14% (Group 1), and men
      with normal morphology > 14% (Group 2). The relationship between percentage of
      normal sperm morphology and fertilization, cleavage and pregnancy rate was
      analysed. The rates were 33.7%, 57.1% and 0.0% respectively, in the first group.
      The corresponding values for the second group were 76.1%, 68.2% and 32.1%. The
      fertilization and pregnancy rates correlate significantly with morphologically
      normal spermatozoa. In regard to the percentage of morphologically normal
      spermatozoa stained with aniline blue, patients were divided into two groups:
      patients with 0-20% stained spermatozoa (Group I) and those with > 20% (Group 2).
      Fertilization and pregnancy rates were higher in the first group than in the
      second group (79.9%, 52.8% vs. 58.8%, 29.5%). The results demonstrate that
      chromatin condensation visualized by aniline blue staining is a good predictor
      for IVF outcome and should be considered besides morphology by sperm assessment
      for patients undergoing IVF treatment.

PMID- 9567168
TI  - Effects of very high doses of human growth hormone (hGH) on the male reproductive
      system in the dog.
AB  - The effects of very high doses of human growth hormone (hGH), pituitary derived
      or recombinant methionyl-hGH, on the morphology of reproductive organs and on
      some hormones in the male dog are described. The studies were part of a
      toxicological documentation of hGH. A total of 18 male dogs aged 7.5-20.5 months,
      from four studies were treated subcutaneously with hGH for 20-28 days at dose
      levels of 3, 10 or 25 IU kg-1 day-1 or 1 IU kg-1 three times weekly. Plasma
      levels of luteinizing hormone (LH), testosterone and prolactin were determined in
      one study. Organ weighing, macroscopic and histopathologic examinations of male
      reproductive organs at the end of the treatment period were included in all
      studies. Treatment with 25 IU kg-1 day-1 resulted in reduction of testis and
      prostate weights, degeneration of germ cells and epithelial atrophy in the
      testis, degenerative changes in epididymis and reduced height of the prostatic
      epithelium. Similar, although less severe morphological changes were observed
      after treatment with 10 IU kg-1 day-1. Treatment with 25 IU kg-1 day-1 also
      caused a marked reduction of plasma prolactin, LH and testosterone levels. These
      results suggest that repeated administration of very high doses of hGH interferes
      with the hormonal regulation of the testis in the dog.

PMID- 9567169
TI  - Human sperm morphology and in vitro fertilization: sperm tail defects are
      prognostic for fertilization failure.
AB  - The aim of this study was to determine the relationship between sperm morphology
      and fertilization rates in vitro. Semen samples were obtained from 50 couples
      undergoing IVF treatment. Sperm morphology was classified by strict criteria
      (Tygerberg) according to head, midpiece and tail defects in neat semen and after
      sperm selection by Percoll gradient centrifugation. Percoll preparation
      significantly increased the percentage of sperm with normal morphology from 13 to
      20%. However, the greatest single regression coefficient was observed with the
      percentage of sperm with tail defects and correlated negatively with
      fertilization rates in vitro both before and after Percoll preparation.
      Therefore, tail morphology may be of value as a prognostic factor in assisted
      conception both before and after Percoll preparation.

PMID- 9567170
TI  - Direct measurement of the tail beat frequency of human sperm by flash light
      synchronization.
AB  - Based on the synchronization between a periodic vibration and flashing light, we
      designed a device to determine the flagellar beating frequency of human sperm.
      The head of a spermatozoon was either held by the tip of a micropipette operated
      with a micromanipulator or adhered by itself on the surface of a glass slide when
      the sperm swam out of the micropipette into the fresh Ham's F-10 medium. The beat
      frequency of the flagellum was measured by synchronization of the frequency
      adjustable flash light built on an inverted microscope. The light frequency
      synchronizer included a controller, a pulse generator, a signal counter, and a
      flash illuminator. During each measurement, the spermatozoon was transferred to
      the center of the observing field and the frequency generator created a series of
      signals which developed flashing signals onto the sample plane. When the
      vibration of the flagellum was observed as a constant two-step-like movement
      after frequency adjustment, the beating frequency was read from the signal
      counter and the count was twice that of the beat frequency of the sperm tail. As
      the flash signal was decreased to half of this frequency, an apparently
      immobilized sperm flagellum was observed and the exact beating frequency could
      then be determined. This device was then used to measure the effect of
      pentoxifylline on sperm motility. The results showed that the increase of tail
      beat frequency as measured by this device is well correlated with the increase of
      beat cross frequency as detected by a computer-assisted semen analyzer. These
      findings suggest that this flash light synchronization device is a reliable and
      useful system for the assessment of sperm motility.

PMID- 9567171
TI  - Declining sperm quality in men of childless couples.

PMID- 9567172
TI  - [Applicability of molecular electrostatic interaction models to describing ionic
      strength dependence of reaction rate between myoglobin and cytochrome c].
AB  - The nonlinear regression method was used for the evaluation of applicability of
      the known model equations (Wherland-Gray, Bronsted-Debay-Hukkel and "parallel
      disks") which describe the ionic strength dependence of the reaction rate between
      charged molecules to the redox reaction of cytochrome c with sperm whale
      myoglobin modified at His 12(A10) with the bromoacetate spin label, and pig
      myoglobin. Unlike the native sperm whale Mb studied earlier [1], the objects
      chosen have monotonous pH-dependence of the reaction rate and are more simple
      with regards to electrostatic interactions in the electron-transfer complex. This
      allowed to study the influence of the total as well as the local protein charge
      on the correspondence of the ion strength dependencies to the theoretical models
      and optimal parameters of the equations. It was shown that the models considered,
      as in the case of the native sperm whale Mb-Cyt c reaction, permit satisfactory
      description of the experimental data, but the obtained parameters cannot be
      applied to the whole proteins or their contact sites. In the best case (Wherland
      Gray equation) it is possible to do if the distribution of electrostatic
      potential in the contact area is considered. The reason can be that, unlike other
      protein redox-systems, the contact sites of both Mb and Cyt c have the charged
      residues of both signs, and the His GH1 residue located in the contact Mb site is
      not only involved in the electrostatic interactions in electron-transfer complex,
      but also participates directly in the mechanism of charge transfer.

PMID- 9567173
TI  - [Elastic properties of triclinic crystals of lysozyme in anhydric acetonitrile].
AB  - Measurements of lysozyme crystal elastic properties in anhydrous acetonitrile
      were performed in order to investigate the role of water in protein elasticity.
      It was shown that triclinic crystals of lysozyme are suitable for such kind of
      investigation because of being placed in acetonitrile they save crystal lattice
      parameters. The observed changes of lysozyme crystals elastic properties are
      close to those found earlier for partially dehydrated protein. These results
      point to water influence on intramolecular conformational mobility of protein.
      The water-protein electrostatic interaction and Laplase's pressure as possible
      mechanisms of this influence are discussed.

PMID- 9567174
TI  - [Inhibition of endogenous oxidation of DNA by spin traps].
AB  - It was shown that spin trap feeding resulted in a decrease of oxidation of rat
      DNA. This is an evidence of free radical mechanism of endogenous DNA oxidation.

PMID- 9567175
TI  - [Volume effect and change in compressibility in intercalation of ethidium bromide
      and daunomycin in DNA].
AB  - A combination of high-precision and density techniques was used to investigate
      the binding of ethidium bromide and daunomycin to DNA. It was shown that
      intercalation is accompanied by a decrease in apparent volume and adiabatic
      compressibility of DNA, which were -28 cm3mol-1 and -20.10(-4) cm3mol-1bar-1 for
      binding of ethidium to DNA, and -28 cm3mol-1 and -18.10(-4) cm3mol-1bar-1 for
      daunomycin, respectively. The values obtained have been compared with those of
      the hydration contributions of atomic groups to the apparent molar volume and
      apparent molar compressibility of the ligands as well as the contribution of
      intrinsic compressibility of DNA. The volume effects in the intercalation of
      ligands correspond to the values expected for the dehydration of aromatic
      heterocyclic rings. On other hand, negative compressibility changes may be
      explained by a decrease of the intrinsic compressibility of DNA and possible
      increase of its hydration as result of conformational changes upon ligand
      binding.

PMID- 9567177
TI  - [DNA inside bacteriophage lambda forms a Z-form].
AB  - The site of the transition regions between the B- and Z-forms of the DNA duplex
      (B-Z junction) may serve as marker of the existence of Z-DNA in situ. The
      structure of (dC-dG)10 insert in the bacteriophage lambda gt10 has been studied
      in situ by modification of B-Z junction with O-beta
      diethylaminoethylhydroxylamine (OHA). The latter is an analogue of hydroxylamine
      possessing specificity with respect to unpaired cytidine. This modification
      inhibited the process of restriction at BamHI site adjacent to the Z-insert.
      Judging by the extent of the inhibition about 5% of all inserts has been
      converted in Z-form. The certain role of Z-form at process of the packaging DNA
      into bacteriophage's capsid suggest.

PMID- 9567176
TI  - [Calorimetric study of the helix-coil transition in DNA during interaction with
      Cu2+ ions].
AB  - Using the method of differential scanning calorimetry, the DNA helix-coil
      transition was studied in solutions (10(-3) M Na+, 10(-3) M tris HCl, pH 7.0)
      containing divalent copper ions at relative metal ion concentrations (Mt2+/PDNA)
      ranging from 0.2 to 20. Dependences of the melting temperature and enthalpy on
      relative ion concentration were determined. An aggregation of Cu(2+) + DNA
      complexes in the range of average ion concentration was established. It is shown
      that the melting enthalpy of "units" increases with copper ion concentration. The
      data obtained were compared with values determined by UV-spectroscopy.
      Association constants for Cu2+ binding to DNA were defined by the ligand theory.

PMID- 9567178
TI  - [Lipid pores and life time of lipid bilayer membranes in gel and liquid crystal
      states].
AB  - The lifetime of lipid bilayer membranes formed from hydrogenated egg lecithin has
      been studied at the phase transition from liquid crystalline state to the gel. It
      was shown the lowering of the membrane stability at the phase transition
      temperature of hydrogenated egg lecithin. Using lifetime values and measured
      surface tension of bilayer the critical radius of transmembrane pore has been
      evaluated in comparison with experimental data, obtained by transmembrane current
      fluctuation registration. It was shown that lifetimes of bilayer lipid membrane
      in gel state conform data, derived from Deryagin-Gutop-Prokhorov's theory. The
      radii of pores corresponded to maximal transmembrane current fluctuations are
      close to critical values of pores in the gel state.

PMID- 9567179
TI  - [Conductivity fluctuation of lipid bilayer membranes formed on a substrate].
AB  - In the range of voltages -0.9-(+)0.9 V the fluctuations of conductivity of
      bilayer lipid membranes formed on the support (s-BLM) were measured. The new cut
      of the wire from stainless steel SS-10T served as the support. The similarity of
      current fluctuations for s-BLM as well as for support-electrolyte interface was
      observed, some quantitative distinctions are revealed. Three types of
      fluctuations are observed; 1) large current jumps observed as current steps at DC
      channel; 2) small current fluctuations near zero line with the spectrum of 1/f
      alpha type (flicker noise); 3) short current jumps, whose amplitudes are many
      folds higher than mean noise level, and the density of distribution function
      falls off as fluctuation magnitude raised to power 2.5 for s-BLM.

PMID- 9567180
TI  - [H+-K+-exchange in anaerobically grown Escherichia coli bacteria during use of
      various sugars as exogenous energy sources].
AB  - E.coli bacteria, grown in anaerobic conditions, in the medium with glucose,
      lactose or maltose, upon transferring into a fresh medium with the same sugar
      acidify it and accumulate potassium ions with a fixed stoichiometry for the N,N'
      dicyclohexylcarbodiimide-inhibited cation fluxes, which is equal to 2H+ of the
      cytoplasm per one K+ of the medium. Such an H(+)-K(+)-exchange is sensitive to
      osmotic shock. In the medium with lactose or maltose cation fluxes are less and
      the intracellular K+ activity at the moment of maximal accumulation is lower. The
      H(+)-K(+)-exchange with a variable stoichiometry of cation fluxes is lost in
      bacteria, grown in a medium with lactose or maltose.

PMID- 9567181
TI  - [Theoretical analysis of the multistability of pyramidal neurons].
AB  - The two-step switch off the long duration Ca action potential was observed
      recently in neocortex pyramids [1]. The phenomenon was interpreted as an evidence
      of the N-type Ca-channel distribution in isolated loci [1]. We demonstrate here
      that the two-step switch off can be imitated in the model with even channel
      distribution in a reconstructed pyramidal neuron as well. The first high plateau
      of the action potential corresponds to steady polarization of the whole membrane.
      The first switch off of the high plateau to the second low plateau corresponds to
      the switch off of the steady depolarization of the short basal dendrites. The
      steady depolarization of the long apical dendrite is more stable thus the switch
      off of the low plateau is a consequence of the apical dendrite repolarization.
      The model includes N-channel inactivation and a somatic shunt. The shunt may be
      artifactual, due to implement, or natural, due to postspike hyperpolarization.
      Recent experiments [2] have proved that the Ca-channels are located everywhere in
      the pyramidal cell.

PMID- 9567182
TI  - [Key role of plasma membrane receptor domains in carcinogenesis].
AB  - Within the limits of the previously proposed conception concerning the dynamical
      domain organization of receptor molecules in biological membranes the possible
      role of receptor domains (RD) of plasma membranes in the mechanism of
      carcinogenesis is discussed. On the basis of extensive experimental material
      accumulating to present by study of different aspects of carcinogenesis, and
      based on the key role of receptor domains of plasma membranes in this process the
      attempt has been made to build the general theory of carcinogenesis. Particular
      attention is given to the analysis of possible genetically depended changes in
      the system of cell division and cell differentiation control, which may be
      responsible for the appearance of non-malignant and malignant tumours in the
      organism, and also to the consideration of the conditions of the appearance of
      clones of transformed cells with uncontrolled growth in the organism. Differences
      in the molecular mechanisms of the appearance of non-malignant and malignant
      tumours are explained.

PMID- 9567183
TI  - [Multiparametric model for regulating the rate of somatic cell proliferation].
AB  - A mathematical model is proposed, which describes the dependence of cell
      proliferation rate on the composition of culture medium. The model uses no
      kinetic relations. The main assumption of the model is that the modification of
      the composition of culture medium changes the properties of cells in the A-state
      of cell cycle. This results in changes in the rates of subsequent intracellular
      processes and hence of cell proliferation. Numerical results are presented, which
      characterize the behaviour of a model culture, which is similar in
      characteristics to the cell 3T3 cell culture. The results do not contradict the
      known facts and may be used for further development of the model.

PMID- 9567184
TI  - [Variant of the Hodgkin-Huxley model with a reduced number of parameters].
AB  - The time constants of variations in sodium and potassium conductances of neural
      cell membrane have been investigated as a function of transmembrane potential. It
      is shown that the dependences can be described by the model of self-organization
      and self-regulation in open dynamic systems reported early. This approach has two
      advantages over the empirical formulae by Hodgkin and Huxley: 1) the number of
      parameters to be defined is substantially reduced, which simplifies modeling of
      real cells, and 2) the model involves a particular mechanisms by which the
      transmembrane potential regulates the time constants of variations in membrane
      conductance, which can promote further development of theoretical conceptions of
      the action potential generation process.

PMID- 9567185
TI  - [Mechanism of radiation death of human peripheral blood lymphocytes, assessed by
      the DNA-comet method].
AB  - Radiation-induced death of human peripheral blood lymphocytes (HPBL) was studied
      using the comet assay. It has been shown that gamma-irradiation induced
      simultaneously two forms of death, necrosis and apoptosis which may be
      discriminated by the comet assay. Three groups of comets formed by HPBL are
      specified: symmetric/slowly asymmetric comets attributed to viable cells (C0/C1
      class of comets); comets reminding "tear-drop" (C3/C4-class of comets) which are
      characterized by decreased total fluorescence of comet and formed by dying/dead
      (necrotic or apoptotic) cells; intermediate form of comets (C2-class), containing
      head, tail and attributed to cells committed to apoptosis (containing high
      molecular weight fragments of DNA). Kinetics of C2-comets permits detection of
      early stage of apoptotic death of irradiated HPBL.

PMID- 9567186
TI  - [Water exchange in human crystalline lens studied by combined dispersion confocal
      microspectroscopy].
AB  - We have employed the technique of the confocal Raman microspectroscopy to monitor
      water exchange in human eye lens in vitro. Heavy water (D2O) was used as a marker
      of the exchange. Raman spectra in the high frequency range (2200-3500 cm-1) were
      successively recorded at several locations inside the lens in order to register
      dynamics of the replacement of H2O by D2O. The intensities of the Raman peaks at
      2450 cm-1 (OD stretch) and 3390 cm-1 (OH stretch) were used as indicators of
      H2O/D2O exchange, whereas the Raman peak at 2935 cm-1 (CH stretch of protein)
      served as an internal standard. The ratios of the Raman intensities I2450/I2935
      and I3390/I2935 determined the relative concentrations of D2O and H2O,
      respectively. For the quantitative description of the exchange, we proposed a
      diffusion model assuming a constant diffusion coefficient over the volume of the
      lens. We report the results of experiments performed on four fresh and one fixed
      lenses. The diffusion coefficient of D2O in the human eye lens was estimated
      using the least-squares fit of the experimental data.

PMID- 9567187
TI  - [Features of kinetics of thrombocytic thrombi growth in the microcirculatory
      system].
AB  - The nonuniform distribution of thrombocytes in a microvessel is considered in
      terms of a previously advanced phenomenological theory, which describes the
      relationship between the mean blood velocity and thrombus growth rate.

PMID- 9567189
TI  - [Temperature dependence of the electrical activity of wasp cardiac function].
AB  - Changes in the temporal structure and amplitude of electrical fluctuations
      connected with the heart function were revealed by the electrophysiological
      method. In the range of optimum temperatures, high- and low-amplitude impulses
      are predominantly generated. Their amplitudes differ approximately by a factor of
      three. Hypo- and hyperthermia stimulate pauses in heart function. Their duration
      increases with the unfavorable effect of temperature. During the activation of
      heart function, high-amplitude fluctuations are predominantly generated. In cold
      torpor, all forms of electric activity stop, whereas in the active state they are
      resumed.

PMID- 9567188
TI  - [Effect of a series of brief cycles of ischemia and reperfusion on free radical
      centers of isolated rat myocardial tissue].
AB  - Free-radical species of rat isolated hearts, perfused by Langendorf mode before
      and after the ischemic preconditioning, have been studied by the ESR method. It
      has been obtained that the preconditioning results in increasing of
      ubisemiquinone concentration in myocardium, which cause the changes in spectral
      and relaxation characteristics of the ESR signals.

PMID- 9567191
TI  - [Explantation of residual effect].
AB  - The direct spatial-temporal description of oscillations of the internal ear
      basilar membrane, arbitrarily called "oscillographic vision" of these
      oscillations, made it possible to create a model for two systems of auditory
      perception of sound pitch [1]. On the basis of this model, the residual effect is
      explained by the action of the main system, the system of periodicity analysis. A
      procedure of calculating the zone of occurrence of the residuum is described. The
      predominance of the complex of low-frequency constituents of the residual sound
      is explained. A qualitative and a quantitative description of high-frequency
      rectangular pulse shifts induced by the action of the fine structure of these
      pulses are given. The assumption is made that these results can be used for
      comparing the accuracy of the two systems of sound pitch perception.

PMID- 9567190
TI  - [Active form of ribonucleotide reductase and level of free iron in human uterine
      myoma].

PMID- 9567192
TI  - [Self-organization nature of forming speech rhythm (the voice source model].
AB  - The rhythmic structure of the temporal organization for acoustical speech signal
      is outlined on the base of self-organization. Suggested physiologically plausible
      nonlinear dynamics for process in discrete time has agreement with the experiment
      and explains the nature of the speech rhythm. Empirical speech rhythm has a good
      agreement with the model prediction.

PMID- 9567193
TI  - [Genesis of rhythmic activity in a neuronal net model].
AB  - The behavior of the summary activity is learned on the proposed model of neuronal
      net, taking into account the data of the neuronal interactions in Ca3
      hippocampus. The summary activities existence of the own oscillations frequency,
      depending on the synaptic connection weights is found. The hypothesis of this
      phenomena role on the theta-activity genesis in the hippocampus is proposed. The
      change of own oscillations under the influence of the external rhythmic
      excitation, coming on the net is investigated.

PMID- 9567194
TI  - [Effect of irradiation from a personal computer video terminal on estrus
      function, melatonin level, and free radical processes in laboratory rodents].
AB  - Chronic irradiation by the video terminal of a personal computer leads to the
      acceleration of sexual maturation and premature termination of the reproductive
      function, decreases the nocturnal level of melatonin, the content of diene
      conjugates and schiff bases in blood serum of female rats and does not affect the
      intensity of blood serum chemiluminescence in male rats. The data obtained
      indicate that the irradiation by the personal computer video terminal has a
      marked biological effect and may affect adversely the health of users.

PMID- 9567195
TI  - [Mechanisms of distribution and elimination of perfluorocarbons upon multiple
      exposures].
AB  - In clinical practice much more often one meets a necessity of repeated
      administration of fluorocarbon blood substitutes. The 19F(-)-NMR-spectroscopy has
      been used to study the kinetics of the blood and tissue fluorocarbon
      concentration after repeated administration of PFC emulsion. Analysis of the data
      suggests that redistribution of PFCs between organs and blood after their
      repeated administration is under control of Ostwald ripening depending on PFC
      physicochemical properties (water and lipid solubility), emulsion particle
      diameter etc and does not connect with activity of reticuloendothelial system.

PMID- 9567196
TI  - A satellite DNA element specific for roe deer (Capreolus capreolus).
AB  - An abundant tandem repetitive DNA segment (CCsatIII) with a repeat unit of 2.2 kb
      has been found in the genome of roe deer (Capreolus capreolus). It accounts for
      approximately 5%-10% of the genome and is only present in the two species of the
      genus Capreolus. The sequence has no similarity or common motives with other deer
      satellite DNAs and there is no internal repeat structure. A 93 bp fragment is
      homologous to a bovine repeat. Fluorescent in situ hybridisation showed a
      predominant centromeric staining of most chromosomes accompanied by a weak
      interstitial staining of the same chromosomes. On Southern blots, CCsatIII probes
      do not discriminate between the closely related Capreolus species.

PMID- 9567197
TI  - Nested insertions of short mobile sequences in Drosophila P elements.
AB  - A potentially full-sized P element isolated from the genome of Drosophila ambigua
      by polymerase chain reaction amplification was completely sequenced. It has a
      length of 3329 bp and the termini are formed by 33 bp inverted repeats. Sequence
      comparisons show that it can be classified as a member of the T-type P element
      subfamily. The translational reading frames of all four exons are interrupted by
      stop codons and frameshift mutations. At the 3' end of exon 3 a 687 bp insertion
      sequence (IS-amb-P) is found that also occurs in the form of dispersed copies (IS
      amb) in the genome in D. ambigua. At the interspecific level it shows homology to
      mobile sequences of other species of the obscura group. Although variable in
      length, these IS elements are characterized by conserved sections without coding
      function and by 14 bp inverted repeats, one at a terminal, the other at a
      subterminal position. In situ hybridization revealed that P elements in D.
      ambigua are restricted to only two euchromatic sites on chromosome elements A and
      E. This situation resembles that found in Drosophila guanche and Drosophila
      subobscura where P homologs are clustered at a single site on chromosome element
      E and where the section corresponding to exon 3 of P elements carries an IS
      element. The gene sik-hom, which is located at the 5' side of the D. guanche
      cluster of P homologs, was used as a marker to examine whether the P element
      sites on chromosome element E of D. guanche and D. ambigua are homologous. The
      results suggest that the nested insertions of IS elements into P elements must
      have occurred independently in the two different lineages.

PMID- 9567198
TI  - Highly repetitive DNA sequences that are restricted to the germ line in the
      hagfish Eptatretus cirrhatus: a mosaic of eliminated elements.
AB  - The New Zealand hagfish, Eptatretus cirrhatus, is known to eliminate parts of its
      chromosomes during embryogenesis from presumptive somatic cells. Electrophoresis
      of germ line and somatic DNAs of this species, after treatment with the
      restriction endonucleases DraI and EcoRI, revealed three fragments of DNA that
      were restricted to the germ line. DNA filter hybridization experiments
      demonstrated that these fragments were present almost exclusively in the germ
      line DNA of E. cirrhatus and that they were highly and tandemly repeated. Thus,
      these DNA fragments appeared to be eliminated during embryogenesis. Moreover, one
      fragment (a DraI fragment) cross-hybridized with the germ line DNA from other
      species of hagfish, namely, Eptatretus okinoseanus and Paramyxine atami.
      Molecular cloning and sequence analysis revealed that the DraI fragment was
      composed mainly of closely related sequences of 85 bp in length and that this
      sequence was about 75% homologous to the sequence of EEEo2 (eliminated element of
      E. okinoseanus 2) which is a germ line-restricted and highly repetitive sequence
      that was isolated previously from E. okinoseanus. The other two fragments were
      composed of three families of closely related sequences that were 172 bp long
      (designated EEEc1), 61 bp long (EEEc2) and 54 bp long (EEEc3). Fluorescence in
      situ hybridization experiments revealed that each eliminated element was
      distributed on several chromosomes that are limited to germ cells. EEEo2 was
      dispersed on 12 C-band-positive chromosomes. EEEc1 and EEEc3 were dispersed on
      all C-band-positive and several C-band-negative chromosomes. By contrast, EEEc2
      was located to terminal regions of several C-band-negative chromosomes. These
      results suggest that the eliminated chromosomes in hagfish are mosaics of highly
      repeated, germ line-restricted families of DNA sequences.

PMID- 9567199
TI  - Activation of SV40 DNA replication in vivo by amplification-promoting sequences
      of the mouse ribosomal gene cluster.
AB  - Mouse genomic DNA sequences from the region upstream of the ribosomal genes
      reported to contain amplification-promoting activity (APS1 and APS2) were tested
      for their ability to support SV40 replication in vivo. Both APSs can functionally
      replace the auxiliary sequence 2 on the late side of the SV40 origin, which
      facilitates initiation of replication. This stimulatory activity on the SV40
      origin was orientation independent and was exerted over a distance of at least
      0.9 kb. However, the APS2 element can not substitute for the auxiliary sequence 1
      on the early side of the origin. Although both APS elements contain various
      prospective transcription factor binding sites, they do not trans-activate
      transcription from a minimal promoter. In this respect they differ from the
      enhancer element of the auxiliary sequence 2 of the SV40 origin. These results
      suggest that the rDNA sequences tested contain genetic information facilitating
      replication initiation on a viral core origin.

PMID- 9567200
TI  - Preparation and imaging of nuclear spreads from cells of the zebrafish embryo.
      Evidence for large degradation intermediates in apoptosis.
AB  - We describe a method for preparing nuclear spreads from cells of live, unfixed
      zebrafish embryos at the late-gastrula (approximately 8000 cell) stage of
      development. The method consists of a sequence of four steps: (1) a slow, gentle
      lysis, in low to moderate salt concentration, of cells and then nuclei, to
      release DNA-containing fibres; (2) spreading of the released fibres by a
      transverse fluid flow; (3) electrostatic, and possibly also covalent, attachment
      of the spread fibers to poly(L-lysine)-coated glass microscope slides; and (4)
      continued incubation to produce periodic cleavage of the DNA within the fibres,
      apparently through activation of endogenous nucleases. The nuclear spreads are
      imaged with epifluorescence, at a spatial resolution approaching the Rayleigh
      limit (approximately 230 nm for blue light). The epifluorescent signal is
      provided from Hoechst 33,258 bound specifically to the DNA, from a dye-coupled
      antibody conjugate bound specifically to histone H1 in the fibres, or from a DNA
      nick end-labelling assay. The spontaneous cleavage of DNA-containing fibres in
      step (4) of the above procedure can be blocked by the chelating agents EGTA and
      EDTA, by the caspase-2,3,7 inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde, and by
      the caspase-1,4,5 inhibitors N-acetyl-Tyr-Val-Ala-Asp-aldehyde and N-acetyl-Tyr
      Val-Ala-Asp-chloromethyl ketone. These data suggest that the spontaneous cleavage
      of fibres is catalysed by nucleases that become activated through a caspase
      mediated mechanism. The involvement of caspase-dependent nucleases would suggest
      that an apoptosis pathway is activated in the spreads during their prolonged
      incubation. If bona fide apoptosis is induced in living zebrafish embryos by
      treatment with camptothecin (a topoisomerase I poison), and then nuclear spreads
      are prepared, we observe a similar fragmentation of the spread fibres. However,
      in this case the fragmentation is more rapid and complete. We hypothesize that,
      during the early phase of apoptosis, one or more endogenous nucleases are
      activated by a caspase-mediated mechanism. The nuclease(s) then specifically
      recognize and cleave a susceptible, periodically repeating feature of interphase
      chromatin.

PMID- 9567201
TI  - Defining the anatomy of the Rangifer tarandus sex chromosomes.
AB  - A comprehensive cytogenetic characterization of the unusally large reindeer
      (Rangifer tarandus) sex chromosomes is presented for the purpose of studying the
      evolution of these atypical gonosomes. Sex chromosome idiograms were constructed
      from G-banded and C-banded chromosomes to illustrate the relative amounts and
      locations of euchromatin and heterochromatin. Hybridization with a Mazama
      gouazoubira X whole-chromosome paint revealed that essentially all reindeer X
      linked euchromatin and most reindeer Y-linked euchromatin is conserved
      interspecifically. Subsequently, painting probes were generated from flow-sorted
      reindeer X chromosomes, flow-sorted reindeer Y chromosomes, and from
      microdissections of specific gonosomal regions to establish specific segment-to
      segment homologies between these gonosomes. In particular, one microdissection
      generated paint demonstrated that certain constituent repetitive DNAs, found in C
      band region Xq31, were also present in essentially all heterochromatin blocks of
      the Y chromosome. Microdissection-generated paints from other X-linked
      heterochromatin blocks revealed the presence of DNA sequences that lacked
      homologous sequences on the Y chromosomes and were more specific for their region
      of origin. These characteristics of the reindeer sex chromosomes are consistent
      with the notion that mammalian sex chromosomes were derived from homologous
      progenitor chromosome pairs and provide insights into the evolution of these
      atypical mammalian gonosomes.

PMID- 9567202
TI  - Fibromyalgia, chronic fatigue syndrome, and myofascial pain.
AB  - Epidemiologic studies continue to provide evidence that fibromyalgia is part of a
      spectrum of chronic widespread pain. The prevalence of chronic widespread pain is
      several times higher than fibromyalgia as defined by the 1990 American College of
      Rheumatology guidelines. There is now compelling evidence of a familial
      clustering of fibromyalgia cases in female sufferers; whether this clustering
      results from nature or nature remains to be elucidated. A wide spectrum of
      fibromyalgia-associated symptomatology and syndromes continues to be described.
      During the past year the association with interstitial cystitis has been
      explored, and neurally mediated hypotension has been documented in both
      fibromyalgia and chronic fatigue syndrome. Abnormalities of the growth hormone
      insulin-like growth factor-1 axis have been also documented in both fibromyalgia
      and chronic fatigue syndrome. The commonly reported but anecdotal association of
      fibromyalgia with whiplash-type neck trauma was validated in a report from
      Israel. However, unlike North America, 100% of Israeli patients with
      posttraumatic fibromyalgia returned to work. Basic research in fibromyalgia
      continues to pinpoint abnormal sensory processing as being integral to
      understanding fibromyalgia pain. Drugs such as ketamine, which block N-methyl-D
      aspartate receptors (which are often upregulated in central pain states) were
      shown to benefit fibromyalgia pain in an experimental setting. The combination of
      fluoxetine and amitriptyline was reported to be more beneficial than either drug
      alone in patients with fibromyalgia. A high prevalence of autoantibodies to
      cytoskeletal and nuclear envelope proteins was found in chronic fatigue syndrome,
      and an increased prevalence of antipolymer antibodies was found in symptomatic
      silicone breast implant recipients who often have fibromyalgia.

PMID- 9567203
TI  - Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.
AB  - Low-income populations have a lower prevalence of low back pain than high-income
      populations. Pathologic processes affecting the intervertebral disc are affected
      by genetic factors and degeneration of annular fibers. Historical and physical
      findings are not helpful in identifying damaged tissues in patients with
      nonspecific low back pain. Agency for Health Care Policy and Research guidelines
      for plain radiographs in the evaluation of low back pain are too sensitive and
      expose patients unnecessarily to ionizing radiation. Clinical entities reviewed
      in the literature include septic sacroiliitis, prognosis of metastatic spinal
      tumors, and low back pain in health care professionals. Epidural corticosteroid
      injections are useful for leg pain and sensory deficits early in the course of
      sciatica secondary to a herniated nucleus pulposus. Poor nutritional state
      increases the risk for postoperative infections for spinal fusion patients.

PMID- 9567204
TI  - Cervical spine disorders.
AB  - Recent research of disorders of the neck has concentrated on the efficacy of
      manual and other conservative therapies for neck pain and whiplash. Systematic
      reviews paint a poor picture of the quality of literature upon which many
      conventional, conservative therapies are based. Conclusive scientific data are
      lacking. Despite its unsavory reputation, whiplash has attracted considerable
      scientific inquiry. Multiple studies have brought data to bear that indicate that
      chronic neck pain after whiplash is not psychogenic, and that psychologic
      distress is secondary to the pain. Strong studies have shown that cervical
      zygapophysial joint pain is the most common basis for chronic neck pain after
      whiplash but that this condition cannot be diagnosed other than by using
      controlled diagnostic blocks. Surgical treatment of cervical zygapophysial joint
      pain has been proven to be effective in a double-blind controlled trial.

PMID- 9567205
TI  - Surgery of the rheumatoid foot and ankle.
AB  - Numerous reconstructive procedures have been used to address the manifestations
      of rheumatoid arthritis in the foot and ankle. Clinical studies have documented
      that these procedures relieve pain, however they often sacrifice motion essential
      to the normal function of the foot. In the forefoot, metatarsophalangeal joint
      resection arthroplasty shortens the lever arm of the foot, defunctions the toes,
      and disables the plantar plate and fat pad. Arthrodesis of the ankle and hindfoot
      alters gait and the effective transmission of weight-bearing stresses through the
      foot and ankle. These ablative procedures may provoke the deterioration of
      adjacent joints and may cripple the long-term function of the lower extremity.
      The introduction of reconstructive procedures designed to preserve motion in
      joints essential to function and the recognition and treatment of muscle
      imbalances associated with bone and joint deformities are recent advances in the
      surgical management of the rheumatoid foot and ankle.

PMID- 9567206
TI  - Epidemiology and health services research.

PMID- 9567207
TI  - Update on clinical trials in the rheumatic diseases.
AB  - Therapeutic trials in rheumatoid arthritis (RA), osteoarthritis, seronegative
      spondyloarthopathies, back pain, systemic lupus erythematosus, and systemic
      sclerosis are reviewed. For RA, minocycline has been proven effective in some
      subsets of RA, whereas tumor necrosis factor receptor IgG fusion protein appears
      quite effective for treating the symptoms of RA in a more resistant group. The
      latter trial illustrates the importance of tumor necrosis factor in RA. Also, the
      triple combination of hydroxychloroquine, sulfasalazine, and methotrexate is very
      effective even in resistant RA. In osteoarthritis, the effects of nonsteroidal
      anti-inflammatory drugs, intra-articular steroids, and biologics are reviewed,
      with generally nondifferentiable nonsteroidal anti-inflammatory drug effects and
      some short-term intra-articular effects of new biologics. Sulfasalazine is
      moderately effective for ankylosing spondylitis and psoriatic arthritis, although
      the large placebo response in the latter makes it more difficult to show
      responses. Trials in the treatment of back pain are beginning to be published,
      with a large cohort study over 1 year favoring surgery for early relief of pain
      in both sciatica and lumbar stenosis, but not showing a clear advantage in
      functional outcome at 1 year. Finally, early reports show the ability of
      dihydroepiandrosterone to decrease steroid use in systemic lupus erythematosus,
      whereas Relaxin appears to be effective in decreasing skin involvement in
      systemic sclerosis. These trials demonstrate in numerous ways the need to
      consider the elements of good trial design when testing therapeutic modalities in
      the rheumatic diseases. These key elements include 1) careful patient definition
      and selection; 2) removal of bias (requiring blinding, randomization, prospective
      studies, and often, placebo); 3) use of well-defined outcomes; and 4) careful
      analytic techniques.

PMID- 9567208
TI  - Update in the epidemiology of the rheumatic diseases.
AB  - The epidemiology of early synovitis syndromes in the community remains of
      interest. Attempts to identify those cases likely to progress to erosive
      rheumatoid arthritis have yielded some prognostic features that may be clinically
      applicable. The incidence of juvenile rheumatoid arthritis appears to fluctuate
      in a cyclic pattern, suggesting microbial or other environmental factors
      contributing to its occurrence. In the United States, the frequency of
      scleroderma varies among racial groups with rising rates noted especially among
      African-American women. A very high prevalence of scleroderma among Oklahoma
      Choctaws is providing an opportunity to study interactions of environmental and
      genetic risk factors. Excess weight in middle-aged women and possibly low intake
      of antioxidants contribute to the progression of established osteoarthritis of
      the knee.

PMID- 9567209
TI  - A review of cost-effectiveness analyses in rheumatology and related disciplines.
AB  - A MEDLINE search of the 1996 and 1997 literature yielded two reviews of the
      methodology of cost-effectiveness analyses (CEAs) in the field of rheumatology
      and eight original CEAs evaluating slow-acting antirheumatic agents (two
      studies), total hip arthroplasty for patients with osteoarthritis (one study),
      educational intervention for patients with fibromyalgia (one study),
      interventions for patients with low back pain (three studies), and hormone
      replacement therapy for women with osteoporosis (one study). Most CEAs relied on
      modelling of data that were assembled from various sources; however, in one CEA a
      cost-effectiveness comparison was based on data collected prospectively within a
      randomized clinical trial. Extensive sensitivity analyses were conducted by a
      majority of the studies. The CEAs of slow-acting antirheumatic agents provided
      results that were difficult to interpret given extensive modelling and reliance
      on expert estimates. Only one CEA was supported by an industry grant. Most of the
      studies were of high quality and met current methodologic requirements, including
      the use of discounting, sensitivity analysis, and incremental analysis. However,
      the major shortcoming of these recent studies continues to be the use of
      estimated costs instead of prospectively measured resource utilization data
      presented in terms of separate physical units.

PMID- 9567211
TI  - The patient's role in rheumatology care.
AB  - This article reviews narrative and empiric studies in rheumatology and related
      literature to explicate the patient's role in rheumatology care. In contrast to
      early conceptualizations, such as Parsons' sick role that emphasized compliance,
      current literature describes chronic disease patients as active participants in
      their care, rather than passive recipients of care. Active patients roles include
      participant in shared decision making, self-manager, and help and information
      seeker. All of these roles are colored by the individual's need to preserve a
      personally defined acceptable lifestyle. Suggestions for strategies that
      physicians and health professionals can use to engage and support these essential
      patient roles are also reviewed.

PMID- 9567210
TI  - Disability caused by work-related musculoskeletal disorders.
AB  - This article describes the magnitude, extent, and economic consequences of some
      of the more common, work-related musculoskeletal disorders. In addition, it
      provides a brief historic overview of the state-federal vocational rehabilitation
      program in the United States. It identifies and considers a constellation of risk
      factors for work-related disability because of musculoskeletal disorders, and it
      discusses phases of physical rehabilitation as that process relates to injured
      workers. The shifting disability paradigm is examined, and attention is given to
      terminology that has become fashionable since passage of the landmark Americans
      with Disabilities Act of 1990. Finally, various factors and conditions that often
      become barriers to an injured person's successful return to the workforce are
      briefly discussed.

PMID- 9567212
TI  - Nonarticular rheumatism, sports-related injuries and related conditions.

PMID- 9567213
TI  - Epidemiology and health services research.

PMID- 9567214
TI  - P glycoprotein: a new mechanism to control drug-induced nephrotoxicity.
AB  - The role of P glycoprotein (P-gp) in kidney is now being explored, and under
      physiological conditions, this protein is thought to be an excretory pump of
      cationic xenobiotics and metabolites. Functionally, two different types of P-gp
      have been described, but only the class I has been related to drug transport, and
      its overexpression confers the multidrug resistance phenotype in tumoral cells.
      It has been proposed that P-gp is involved in the energy-dependent transport of
      substrates through the cell membrane (toxic metabolites, toxins, nutrients, ions,
      peptides, etc.)--like a 'hydrophobic molecule vacuum cleaner'. Several
      physiological functions have been attributed to P-gp: defense against xenobiotic
      aggression and transmembrane transport of prenylcysteine methyl esters, removing
      these cytotoxic metabolites from cells. A variety of substrates ranging from
      chemotherapeutics to steroid hormones, antibiotics, and calcium channel blockers
      can be transported by P-gp, suggesting the possible involvement of this protein
      in other unknown functions. Results from our group and others have suggested that
      overexpression of P-gp in renal tubular and mesangial cells prevents
      pharmacological nephrotoxicity by cyclosporin A (CsA). On the other hand CsA, a
      substrate of the pump, could act as a blocker in tubular cells by competitive
      inhibition. One relevant aspect in kidney is the possible relationship between P
      gp and protein kinase C. Several reports suggest that protein kinase C may play a
      role in inducing the P-gp overexpression in cells under xenobiotic pressure,
      through activation of the ras oncoprotein family. This could be mediated directly
      by angiotensin II as a ras activator. This way, the detoxicant function of P-gp
      against products of the ras catabolism could mediate their accumulation when the
      'vacuum cleaner' function is blocked by CsA or tacrolimus, contributing to the
      initial development of fibroblastic activation that leads to interstitial
      fibrosis associated with nephrotoxicity by these immunosuppressor drugs. In
      conclusion, P-gp expression could be an important component of a complex
      detoxifying system in kidney against xenobiotics or regulating the traffic of
      endogenous metabolites responsible for the susceptibility of subjects to the
      development of nephrotoxicity against different drugs.

PMID- 9567215
TI  - The charge for going by foot: modifying the surface of podocytes.
AB  - The podocyte is a highly differentiated cell which forms a crucial component of
      the glomerular filtration barrier. It maintains a large filtration surface
      through the slit membranes and counteracts the distension of the glomerular
      basement membrane. The podocyte is covered with an anionic glycocalyx believed to
      be important in the maintenance of foot process structures, but the mechanisms of
      the cellular interaction between podocyte charge and its function are not clearly
      understood. It has been speculated that the charge selectivity of the glomerular
      barrier is influenced by angiotensin II. In experimental models of glomerular
      nephropathy neutralization of the polyanionic surface with polycations causes a
      retraction of podocyte foot processes. The effect of polycations is energy and
      Ca2+ dependent and results in tyrosine kinase induced phosphorylation of proteins
      of the foot processes. Charge alterations of the podocyte seem also associated
      with proteinuria in several human glomerular diseases such as membranous or
      diabetic nephropathy. The knowledge of the interaction between charge and
      podocyte function might offer new strategies in the treatment of glomerular
      diseases.

PMID- 9567216
TI  - Evidence for atrial natriuretic factor induced natriuretic peptide receptor
      subtype switching in rat proximal tubular cells during culture.
AB  - Culture and natriuretic peptide dependent changes in the expression of the
      natriuretic peptides atrial natriuretic factor (ANF), brain natriuretic peptide
      (BNP), and C-type natriuretic peptide (CNP) and the natriuretic peptide receptors
      A, B, and C in primary cultures of rat proximal tubular cells were demonstrated
      using polymerase chain reaction analysis and cyclic guanosine monophosphate
      response to ANF and CNP. Freshly isolated cells expressed mRNA coding for the
      natriuretic peptide receptor C only, with no expression of the natriuretic
      peptides or the natriuretic peptide receptors A or B. At confluence natriuretic
      peptide receptor C expression was lost, while mRNA transcripts for both ANF and
      BNP and the A and B receptors became apparent. The appearance of mRNA transcripts
      for the natriuretic peptide receptors A and B during cell growth correspond with
      a significant increase in the cyclic guanosine monophosphate response to both ANF
      and CNP, confirming the presence of functionally active guanylate cyclase linked
      A and B natriuretic peptide receptors. The observed changes in peptide receptor
      expression during culture were preceded by changes in natriuretic peptide mRNA
      expression, suggesting the possibility that natriuretic peptide receptor subtype
      switching may be under the control of endogenous peptide release. Incubation of
      freshly isolated proximal tubular cells with ANF, BNP, or CNP for 3 h induced
      similar changes in receptor expression. Incubation with ANF induced expression of
      the natriuretic peptide receptor B and CNP while inhibiting natriuretic peptide
      receptor C. Incubation with BNP induced expression of the natriuretic peptide
      receptor B and CNP. Incubation with CNP induced expression of the natriuretic
      peptide receptors A and B and CNP. These results suggest that primary cultures of
      rat proximal tubular cells may experience natriuretic peptide and natriuretic
      peptide receptor subtype switching as they approach confluence under the control
      of endogenously expressed natriuretic peptides.

PMID- 9567217
TI  - AT1-receptor antagonists abolish glomerular MCP-1 expression in a model of
      mesangial proliferative glomerulonephritis.
AB  - BACKGROUND: Glomerular accumulation of macrophages/monocytes (M/M) is a typical
      early feature in the course of anti-thymocyte serum (ATS)-induced nephritis. We
      have previously shown that glomerular synthesis and expression of monocyte
      chemoattractant protein-1 (MCP-1) occurs before influx of M/M and a neutralizing
      anti-MCP-1 antibody reduced this cell infiltrate by one third. The present study
      was undertaken to test the effect of two angiotensin II type 1 (AT1) receptor
      antagonists, losartan and irbesartan, on ATS-stimulated MCP-1 expression as well
      as glomerular influx of M/M. METHODS: Treatment of rats with either losartan or
      irbesartan was started 24 h before administration of ATS. After 24 h, MCP-1 mRNA
      expression was evaluated by RT-PCR and Northern blots. MCP-1 protein was
      determined by Western blots and chemotactic factors released from isolated
      glomeruli were measured by chemotactic assay. Kidney sections were stained for
      rabbit IgG, complement C3, and M/M (ED1 antigen). RESULTS: Both AT1-receptor
      antagonists caused a significant, but not total reduction in MCP-1 mRNA and
      protein expression 24 h after injection of ATS. Treatment with losartan or
      irbesartan also reduced the chemotactic activity of isolated glomeruli from
      nephritic animals. Quantification of ED1-positive cells revealed that losartan as
      well as irbesartan reduced glomerular M/M invagination in nephritic rats by
      approximately 30-50%. However, treatment with AT1-receptor antagonists did not
      influence binding of ATS to mesangial cells and subsequent complement activation
      indicating that the attenuated MCP-1 expression is not due to differences in
      delivery and binding of ATS to mesangial cells. CONCLUSION: Our data indicate
      that short-term antagonism of AT1 receptors abolished the early glomerular MCP-1
      expression and M/M influx. These results indicate that angiotensin II may exert
      immunomodulatory effects in vivo and adds a new mechanism showing how this
      vasopeptide may be involved in the pathogenesis of renal diseases.

PMID- 9567218
TI  - Angiotensin II blockade limits tubular protein overreabsorption and the
      consequent upregulation of endothelin 1 gene in experimental membranous
      nephropathy.
AB  - Proteinuric renal diseases are associated with excessive renal synthesis of
      endothelin 1 (ET-1) either in experimental animals or humans. This has been
      interpreted as an upregulation of ET-1 gene in proximal tubular cells secondary
      to overreabsorption of an unusual amount of filtered proteins. Here we used a
      model of chronic proteinuria, passive Heymann nephritis (PHN), to localize the
      structure of the kidney responsible for excessive ET-1 expression and synthesis
      and to clarify whether drugs that reduce glomerular protein trafficking modified
      the distribution of ET-1 mRNA and the corresponding peptide in the kidney. PHN
      was induced in Sprague-Dawley rats after injection of rabbit anti-Fx1A antibody.
      Group 1 (n = 5) was untreated, group 2 (n = 5) was given daily the angiotensin
      converting enzyme inhibitor lisinopril (40 mg/l) plus the angiotensin II receptor
      antagonist L-158,809 (50 mg/l) from day 7--when rats were already proteinuric--to
      month 12. An additional group of normal rats (n = 5) was used as controls.
      Urinary excretion of ET-1 was significantly increased in PHN rats as compared
      with controls and normalized by the treatment. By in situ hybridization a weak
      signal for ET-1 mRNA was detectable in glomeruli, distal tubular segments, and
      proximal tubules of control kidneys. By contrast, a strong labeling was found in
      the kidneys of rats with PHN which was mainly localized to proximal tubules and
      renal interstitium. The pattern of renal ET-1-like immunoreactivity was
      remarkably consistent with ET-1 mRNA expression. In animals with PHN given the
      angiotensin II blocking therapy, the urinary excretion of proteins normalized,
      and the structural integrity of the kidney was well preserved. In the kidney
      tissue taken from these animals, both ET-1 mRNA and protein staining were quite
      comparable to controls. These data suggest a link between excessive protein
      tubular reabsorption and enhanced renal ET-1 in chronic nephropathies and provide
      a novel explanation for the renoprotective effect in vivo of drugs that, by
      blocking the biological activity of angiotensin II, reduce glomerular protein
      traffic and possible deleterious effects of excessive tubular protein
      overloading.

PMID- 9567219
TI  - Differential response of activated versus non-activated renal fibroblasts to
      tubular epithelial cells: a model of initiation and progression of fibrosis?
AB  - BACKGROUND/AIMS: The mechanisms of initiation and maintenance of renal fibrosis
      remain obscure, but one hypothesis highlights the importance of tubular
      epithelial cell-interstitial fibroblast interactions and suggests that tubular
      injury may be a precipitating factor. The aims of the study were to examine the
      effects of factors of proximal tubular origin on renal fibroblasts expressing
      different levels of smooth muscle actin (SMA; a putative marker of fibroblast
      activation) and to examine the modulation of SMA by extracellular matrix (ECM)
      proteins and transforming growth factor beta 1 (TGF-beta 1), a major profibrotic
      cytokine. METHODS: Primary cultures of rat cortical fibroblasts (CF) and the rat
      kidney fibroblast cell line NRK-49F were (1) cultured on different ECM proteins;
      (2) treated with medium conditioned by rat proximal tubular epithelial cells
      (PTE), and (3) treated with TGF-beta 1. SMA protein expression was examined by
      immunocytochemistry, while expression of MMP-2, MMP-3, TIMP-1, and collagen I
      mRNA was determined by Northern blot analysis or reverse-transcriptase polymerase
      chain reaction. RESULTS: In cells with low basal levels of SMA (CF), serum was
      the most potent inducer of increased SMA expression, although ECM proteins also
      modulated expression. With high basal levels of SMA expression (NRK), ECM
      proteins alone had little or no effect, but acted synergistically with serum to
      stimulate expression. In CF, PTE-conditioned medium (CM) had no effect on SMA and
      TIMP mRNA levels, but suppressed expression of MMP mRNAs. In NRK-49F, PTE-CM
      stimulated SMA and TIMP-1 mRNA levels, but had no effect on MMP mRNA levels.
      Although TGF-beta 1 modulated some cellular responses in NRK-49F, neutralizing
      antibody studies showed it was not the main mediator of the PTE-CM-induced
      effects. CONCLUSIONS: These data suggest (1) that in renal fibroblasts SMA
      expression can be modulated by both serum and ECM proteins and (2) that PTE
      induce a fibrogenic phenotype in both non-activated (low SMA) and activated (high
      SMA) fibroblasts via different mechanisms.

PMID- 9567220
TI  - The HVJ liposome method.
AB  - Recent advancement of gene technology allows us a practical approach to gene
      therapy. Among various in vivo gene transfer techniques available, the HVJ
      liposome method is an efficient procedure which could target the glomerular
      cells. Using this method, HVJ-mediated cell fusion activity enables us to
      introduce genetic materials directly into the cytosol without degradation. In
      addition, cointroduction of non-histone nuclear protein, high-mobility group (HMG
      1), efficiently facilitates migration of foreign DNA to the nucleus. Although
      there still exist some limitations, the HVJ liposome method may be applicable to
      the treatment of glomerular diseases as well as to analysis of the molecular
      aspects of renal pathophysiology.

PMID- 9567221
TI  - Glycosyl phosphatidylinositol anchor.
AB  - Recently, we and others demonstrated the unique potential for glycosyl
      phosphatidylinositol (GPI) anchored proteins to transfer from one cell membrane
      to another in a process we termed 'painting'. The GPI-anchored proteins were
      shown to transfer intact and functional. The full significance of this phenomenon
      has yet to be fully realized, but implications exist in many areas including
      disease transmission (prions), cell protection (endothelial cells), and
      senescence (erythrocytes). It is of interest to note that cells exhibiting
      limited or no biosynthetic capacity (spermatozoa and erythrocytes) have been
      implicated thus far in cell-cell transfer of GPI-linked molecules. This
      observation demonstrates the potential for GPI-linked proteins to be 'painted'
      onto cells which otherwise may be incapable of expressing exogenous proteins. We
      show in this paper that GPI-linked CD59 and decay-accelerating factor will
      transfer intact from erythrocytes to endothelial cells in transgenic mice. We
      also demonstrate that the transfer process occurs under physiological conditions
      using several experimental models including organ and bone marrow
      transplantation. We detail the procedure to effect transfer of GPI-linked
      proteins from one cell type to another in either an in vivo or in vitro system.

PMID- 9567222
TI  - The effect of a restricted smoking policy on motivation to quit smoking in
      psychiatric patients.
AB  - As dissatisfaction with unrestricted smoking in institutional settings has grown,
      a number of psychiatric facilities have banned smoking. A compromise, restricted
      smoking, was recently introduced on an inpatient psychiatric unit at a University
      of Michigan Hospital. The subsequent rescission of the restricted smoking policy
      enabled us to compare the effects of restricted smoking vs. ad lib smoking on
      motivation to quit smoking. METHOD: Current smokers admitted to an inpatient
      psychiatry unit were asked to participate in this study. As soon as possible
      after intake, the patient completed a smoking history questionnaire, depression
      and anxiety scales, and a stage of change measure. The stage of change measure
      was readministered upon discharge from the unit. RESULTS: Repeated measures ANOVA
      revealed an interaction for Condition (Restricted vs. Ad Lib) by Time (Admission
      vs. Discharge) for the Action scale, which assesses current level of activity in
      smoking cessation efforts. Restricted smokers decreased while ad lib smokers
      increased in motivation over time. CONCLUSIONS: Results suggest that the
      restricted smoking policy does not have beneficial motivational effects.
      Alternative strategies for controlling smoking on an inpatient psychiatric unit
      are suggested.

PMID- 9567223
TI  - Interest in smoking cessation among methadone maintained outpatients.
AB  - The prevalence of cigarette smoking among opiate abusers is extremely high and
      tobacco related diseases are a major factor associated with morbidity and
      mortality for this group. Yet, many treatment providers remain reluctant to
      address smoking cessation with their clients due in part to the belief that
      substance abusers are not interested in quitting smoking. The present study
      examined self-reported interest in smoking cessation among methadone maintenance
      clients (N = 120) in four clinics in Los Angeles. Fifty-eight percent of subjects
      rated themselves as 'Somewhat' or 'Very Interested' in a smoking cessation
      program. Overall subjects appeared to accurately perceive the personal risks from
      tobacco smoking. In conclusion we find that clients in methadone maintenance
      treatment programs evidence a high level of interest in quitting smoking and may
      well be suited for a highly structured smoking cessation intervention.

PMID- 9567224
TI  - Substance abuse and the emergency room: programmatic implications.
AB  - A literature review (1984 to 1995) was conducted to identify cost effective
      policy implications regarding substance use in the emergency room (ER) and trauma
      unit. Prevalence rates, ranging from 9% to 47%, vary according to where, when and
      who is tested. Other drugs, most commonly marijuana, benzodiazepines and cocaine,
      follow a similar pattern to alcohol. The optimal method of measuring substance
      use depends on the goal of the assessment and a combination of clinical, self
      report and biochemical markers is recommended. Simple screening questions such as
      the TWEAK or AUDIT should be routinely used with all attendants and further
      assessment provided only when high risk factors have been identified. These
      include: males, younger patients, metropolitan centres, after midnight and on
      weekends, injury from violence, accidents including MVAs, high acuity and
      psychiatric morbidity. Further, this screening should be complimented by an
      intervention, referral and treatment resource for those in need.

PMID- 9567225
TI  - Four addictions: the MMPI and discriminant function analysis.
AB  - Over the past twenty years many MMPI studies of substance abuse have investigated
      the complex relationship between personality profile and drug of choice. This
      work has repeatedly established that alcoholics, heroin, cocaine and polydrug
      addicts share 4-2/2-4 (Psychopathy and Depression) or 4-8/8-4 (Psychopathy and
      Thought Disorder) MMPI profiles, but that the substance abuse populations differ
      in the plane of severity in that general profile. The alcoholics occupy the least
      disturbed sector, the polydrug abusers the most disturbed level and the heroin
      and cocaine addicts positions of moderate disturbance. The vast majority of
      studies, however, cite only group means to buttress their conclusions. Our work
      probed more deeply into the data using Discriminant Function Analysis. With this
      methodology we discovered important differences between the groups, previously
      hidden, which may carry differential treatment implications.

PMID- 9567226
TI  - Efficiency and validity of commonly used substance abuse screening instruments in
      public psychiatric patients.
AB  - BACKGROUND: The more commonly used screening instruments for substance abuse were
      largely developed for addictive populations. We compared several alcohol and drug
      abuse scales to determine their efficiency and validity for psychiatric patients.
      METHOD: The subjects were 100 consecutively admitted patients to a public
      psychiatric facility. DSM-III-R diagnoses, obtained from the alcohol and drug
      scales of the SCID-P, were the criterion measure. Methods of reliability included
      inter-rater agreement, estimates of internal consistency, and repeat test
      administration. Sensitivity, specificity and more infrequently used accuracy
      indices, such as likelihood ratios and Receiver Operating Characteristic (ROC)
      analysis, were utilized to assess scale validity. RESULTS: First, the reliability
      of all scales was high. Second, the instruments generally demonstrated highly
      acceptable levels of screening accuracy. Third, the intake evaluation was as
      reliable and valid as screening after admission on the unit. Finally, instruments
      were least discriminating for current problems (past 30 days). CONCLUSIONS:
      Lifetime measures were found to be reliable and valid for public psychiatric
      patients but further research is need on increasing the accuracy of screening for
      current substance abuse problems and the effectiveness of multiple screening
      approaches.

PMID- 9567227
TI  - A field application of the ASAM placement criteria in a 12-step model of
      treatment for chemical dependency.
AB  - Procedures followed in the development of a standardized method of rating patient
      behavior relevant to engaging in a 12 step model of recovery are presented in the
      context of deriving an empirical cross-walk for the ASAM PPC. This instrument
      permits addictions counselors to rate the severity of operationally defined
      behaviors on each of the six criteria dimensions identified in the adaptation of
      the PPC by the WV Division on Alcoholism and Drug Abuse for use in the 14 member
      community mental health centers funded by the state. Substance dependent adults
      (N = 78), who self-selected either residential or partial day treatment at
      EastRidge's Addictions Treatment Center were evaluated with this procedure over a
      nine month period. Intercorrelations of ratings on six criteria dimensions at
      intake ranged from .053 to .576 and after an average length of stay of 18 days,
      behavioral severity on all dimensions was significantly reduced (p < .0001) on
      the discharge evaluation with this tool. An empirically based, treatment matching
      matrix, was constructed from confidence intervals calculated obtained from intake
      data to form norm referenced ranges for four levels of care (which equate to PPC
      2 Levels: III.5, II.5, II.2, I). The utility of this methodology in facilitating
      the application of the WVPC and PPC-2, and the potential of the DRS as a multiple
      baseline measure in treatment outcome research is discussed.

PMID- 9567228
TI  - Differential therapeutics and the impaired physician: patient-treatment matching
      by specificity and intensity.
AB  - The objective of this study was to determine the nature and degree of patient to
      treatment matching for a sample of physicians based on differential problem type
      and severity. Methods included a single assessment of variables using
      retrospective chart review. Subjects included 108 physicians (98 men and 10
      women), who were sampled consecutively from assessments performed over a 2-year
      period. They represented a variety of specialties, and most were third-party
      referred, predominantly by state medical societies. Main outcome measures
      included demographic information, DSM-IV multiaxial diagnoses, the Severity of
      Substance-Related Disorder scale, and the type and intensity of recommended
      treatment. It was found that the physicians presented with a variety of
      conditions that were clustered into three categories: active substance use
      disorders (52.8%), substance use disorders in remission (17.6%), and
      psychiatric/behavioral problems (29.6%). An analysis of the appropriateness of
      matching types of treatment to these problem categories appeared to support a
      differential assignment process. A range in severity was also found within
      problem categories and was subsequently tested for correspondence with the range
      in intensity of recommended treatment. It was found that severity correlated
      strongly with recommended treatment intensity for all groups. In addition,
      multiple regression analyses showed that two factors, ability to sustain
      abstinence and emotional disturbance, were predictive of treatment intensity for
      the two substance use disorder subgroups (64% of variance accounted for). In the
      psychiatric/behavioral problem subgroup, such analysis demonstrated that the
      severity of difficulties with one's significant other was predictive of treatment
      intensity (89% of variance accounted for).

PMID- 9567229
TI  - Reviewing ASAM's goals and accomplishments. American Society of Addiction
      Medicine.

PMID- 9567230
TI  - Public policy statement on definitions related to the use of opioids in pain
      treatment. American Society of Addiction Medicine.

PMID- 9567231
TI  - Vertebral artery flow and spinal manipulation: a randomized, controlled and
      observer-blinded study.
AB  - BACKGROUND: Several studies have been published on the effect of cervical
      rotation alone upon blood flow in the vertebral arteries. However, we have not
      found articles addressing the question of how spinal manipulative therapy per se
      affects the vertebral artery flow. OBJECTIVE: The aim of the present study was to
      investigate whether any changes occur in peak flow velocity in the vertebral
      artery after spinal manipulative therapy as measured using the latest Doppler
      ultrasound technology. DESIGN AND SETTING: A randomized, controlled and observer
      blinded study at a university hospital vascular laboratory. PARTICIPANTS: Twenty
      university students with a "biomechanical dysfunction" in the cervical spine.
      RESULTS: We observed no change in peak flow velocity immediately after spinal
      manipulative therapy and found no correlation between peak flow velocity and
      systolic blood pressure. CONCLUSION: To the best of our knowledge, this is the
      first study comparing flow velocity in the vertebral artery before and after
      spinal manipulative therapy. We found no significant changes in otherwise healthy
      subjects with a biomechanical dysfunction of the cervical spine. Major changes in
      peak flow velocity might in theory explain the pathophysiology of cerebrovascular
      accidents after spinal manipulative therapy. However, in uncomplicated spinal
      manipulative therapy, this potential risk factor was not prevalent.

PMID- 9567232
TI  - Attachments of the ligamentum nuchae to cervical posterior spinal dura and the
      lateral part of the occipital bone.
AB  - OBJECTIVE: To describe previously unrecorded attachments of the ligamentum nuchae
      to the cervical posterior spinal dura, and to posterolateral parts of the
      occipital bone in an anatomical study, with particular reference to the deep
      aspects of the suboccipital triangle and upper cervical region. DESIGN:
      Dissections of 10 heads and necks from embalmed cadavers were made in the
      suboccipital and upper cervical region, either in whole specimens or in
      parasagitally sectioned specimens. RESULTS: In parasagittally sectioned material,
      continuity was observed between the ligamentum nuchae and the posterior cervical
      spinal dura as the latter passed deeply from the midline toward the dura, but
      only at the first and second cervical vertebral levels. The ligamentum nuchae
      also passed bilaterally on to the occipital bone as far as the sutures between
      the occipital bone and the temporal bones, approaching the inferior nuchal line
      superiorly. CONCLUSION: The present study is the first to describe the full
      morphology of the relationship between the ligamentum nuchae and the cervical
      posterior spinal dura and the lateral aspects of the occipital bone. This is of
      significance for understanding the biomechanics of the cervical spine,
      particularly rotational movements of the head in the sagittal or transverse
      planes. This may have implications in manipulative therapy for conditions as
      cervicogenic headache and for various degenerative disorders affecting the
      cervical spine.

PMID- 9567233
TI  - Development of a practice-based research program.
AB  - OBJECTIVE: To establish an infrastructure to collect accurate data from
      ambulatory settings. DESIGN: The program was developed through an iterative model
      governed by a process of formative evaluation. The three iterations were a needs
      assessment, feasibility study and pilot project. Necessary program components
      were identified as infrastructure, practitioner-researcher partnership,
      centralized data management and standardized quality assurance measures. SETTING
      AND PARTICIPANTS: Volunteer chiropractors and their staff collected data on
      patients in their practices in ambulatory settings in the U.S. and Canada.
      OUTCOME MEASURES: Evaluative measures were counts of participants, patients and
      completed forms. Standardized, validated and reliable measures collected by
      patient self-report were used to assess treatment outcomes. These included the SF
      36 or SF-12 Health Survey, the Pain Disability Index, and the Global Well-Being
      Scale. For characteristics for which appropriate standardized instruments were
      not available, questionnaires were designed and and pilot-tested before use.
      RESULTS: Information was gathered on practice and patient characteristics and
      treatment outcomes, but for this report, only those data concerning process
      evaluation are reported. Through the three program iterations, 65 DCs collected
      data on 1360 patients, 663 of whom were new patients. Follow-up data recorded by
      doctors were obtained for more than 70% of patients; a maximum of 50% of patient
      completed follow-up forms were collected in the three iterations. CONCLUSIONS:
      This program is capable of providing data for descriptive epidemiology of
      ambulatory patients, and, with continued effort to maximize follow-up, may have
      utility in providing insight into utilization patterns and patient outcomes.

PMID- 9567235
TI  - The use of Learning and Study Strategies Inventory (LASSI) as a predictor for
      success or failure on part I of the National Board of Chiropractic Examiners
      Test.
AB  - INTRODUCTION: The need for each chiropractic student to pass the National
      Chiropractic Board of Examiners (NCBE) exams is of great importance in their
      educational process. To date, no literature has evaluated the effectiveness of
      any outcome in predicting the success or failure on the NCBE exams. The Learning
      and Study Strategies Inventory (LASSI) was developed to assess students' learning
      and studying strategies. In this study, the LASSI and NCBE Part 1 scores and
      entering and cumulative grade point averages (GPAs) were used to assess any
      correlations related to NCBE scores. METHODS: The LASSI was administered to a
      group of trimester-6 students at Texas Chiropractic College after their
      completion of Part 1 of NCBE exams. The scores were analyzed by computer and
      appropriate statistical procedures were performed. RESULTS: Moderately high
      correlations were found with NCBE scores and each component of the LASSI. There
      were also moderately high correlations found with the NCBE scores and cumulative
      GPAs. Low correlations were found with NCBE scores and entering GPAs.
      CONCLUSIONS: Because of the high correlation of NCBE scores and the LASSI scores,
      it is recommended that this test be introduced to first-trimester students and
      that follow-up correlations be performed with NCBE scores, GPAs and LASSI scores.
      An elective course for students that perform poorly on LASSI could be developed
      to aid students weak in study skills and strategies. The need for further studies
      includes the evaluation of students put through the LASSI and preparation course
      as it relates to their NCBE scores.

PMID- 9567234
TI  - The effects of high and low loading forces on measured values of lumbar
      stiffness.
AB  - OBJECTIVE: One explanation for the poor reliability of manual judgments of
      posteroanterior (PA) stiffness may be that if manual therapists use different
      forces when testing, different stiffness is perceived. This study was conducted
      to examine measurements of lumbar PA stiffness obtained using a device programmed
      to generate different loading forces. SUBJECTS: Twenty-five subjects with no
      history of low back pain and a mean age of 23.5 yr were measured. METHODS:
      Measures of lumbar PA stiffness were obtained using a mechanical device that
      applied a testing force of 200 N to the skin overlying the L3 spinous process.
      Six stiffness coefficients were determined from the force/displacement curve
      obtained from each subject by performing linear regressions from 30-80 N, 30-150
      N, 30-200 N, and from 30-83.3 N, 83.3-136.7 N, and 136.7-200 N. Intraclass
      correlation coefficients and repeated measures analysis of variance were used to
      analyze the data. RESULTS: Although moderate reliability [ICC 2,1 = 0.67] was
      found for stiffness measures arising from increasingly wide force-interval
      regressions (30-80 N, 30-150 N, 300-200 N), poor reliability [ICC (2,1) = 0.39]
      was found for stiffness measures arising from same-width, higher force
      regressions (30-83.3 N, 83-137 N, 137-200 N). In both cases there were
      significant differences between the obtained K stiffness values corresponding to
      different force intervals. CONCLUSION: These results show that if therapists push
      harder, different stiffnesses will be felt. Studies using instrumental
      measurement of spinal stiffness to obtain 'K' values should report the force
      intervals used. Also, revised protocols for manually judging PA stiffness should
      ensure that stiffness is assessed by sampling specified force intervals rather
      than the raters determining their own force limits.

PMID- 9567236
TI  - Raymond L. Nimmo and the evolution of trigger point therapy, 1929-1986.
AB  - Dr. Raymond L. Nimmo (1904-86) was the definitive chiropractic pioneer in the now
      widely accepted field of soft tissue and trigger point therapy. This article
      explores how Nimmo was able to make the radical conceptual leap from moving bones
      to working with muscles that move the bones. Also discussed are the
      neurophysiological explanations that Nimmo evolved in the 1950s for the trigger
      point phenomenon, formulations that are still regarded as highly sophisticated
      half a century later. Finally, the article describes how Nimmo, with a basic
      chiropractic education absent much of the background in the biological and
      physical sciences of today's preparation, was able to combine his clinical
      experiences and intellectual formulation to arrive at a theory that became widely
      accepted.

PMID- 9567237
TI  - Chiropractic utilization of lumbar magnetic resonance imaging: how accurate are
      we compared with other specialties?
AB  - OBJECTIVE: To determine, through the review of lumbar magnetic resonance images
      (MRIs), which specialty ordering these scans was more successful and accurate in
      coming up with "positive findings" that would warrant the use of the modality.
      Such data can demonstrate to managed care organizations and insurance companies
      that chiropractors have a good working knowledge of when to use this test and
      that the profession deserves the right to direct access to MRI. DESIGN: Seven
      hundred and two lumbar MRIs taken over a 3-yr period were reviewed. A list of
      seven criteria was made consisting of (a) disc derangement, (b) stenosis, (c)
      trauma, (d) tumors, (e) hematologic and vascular, (f) infection and (g) metabolic
      endocrine disorders. Scans found to have one of the seven categories were listed
      as positive findings. The number of positives were then entered under each
      separate specialty group and a percentage was calculated for each. RESULTS: This
      study showed that DCs fared better than all providers except for oncologists and
      general surgeons. Chiropractors fared 2.42% better than orthopedists and 10.06%
      better than general practitioners, who, ironically, DCs must rely on at times for
      authorization of MRIs in certain managed care situations. CONCLUSION: It would be
      fruitful to conduct similar studies of this type, thus obtaining a larger
      database of information that reflects more accurate numbers nationwide and
      documents chiropractors' working knowledge of when to use this imaging modality.

PMID- 9567238
TI  - Three-dimensional spinal coupling mechanics: Part II. Implications for
      chiropractic theories and practice.
AB  - OBJECTIVE: To compare the current knowledge of 3-D spinal mechanics and abnormal
      equilibrium states with chiropractic motion theories, chiropractic vertebral
      letter listing theories, and chiropractic technique theories. DATA COLLECTION: A
      manual search of available reference texts and a computer search of literature
      from Index Medicus were collected with an emphasis on 3-D studies of human spinal
      movements, segmental instability, Euler buckling of the spine, and chiropractic
      theories concerning vertebral movements. RESULTS: Previous spinal coupling
      results based upon two-dimensional radiographic studies are inadequate and
      inaccurate. Therefore, the validity of any chiropractic technique procedure,
      listing, motion analysis or adjusting style based on the two-dimensional
      radiograph and coupling studies must be questioned. We have identified four types
      of spinal subluxations (displacements) in the biomechanical literature: (a)
      posture main motion and associated segmental coupling, (b) Euler buckling viewed
      in the anteroposterior view, (c) snap through viewed in the lateral view and (d)
      segmental instability. CONCLUSIONS: Full three-dimensional investigations of
      spinal coupling patterns have shown that the vertebrae rotate and translate in
      all three axes and that previous theories of spinal coupling based upon two
      dimensional studies are inaccurate and invalid. Previous chiropractic letter
      listings (e.g., PRI, PLS, etc.) of spinal displacements are inadequate and
      invalid. Only one of the four types of biomechanical displacements, segmental
      instability, is consistent with the traditional chiropractic theory of segmental
      spinal displacements; in general, this does not respond well to care. In general,
      vertebrae displacement must be viewed in the context of equilibrium
      configurations and one vertebra can not be displaced as an individual
      misalignment. Validity questions arise for any technique methods that use letter
      listings of displacement taken from motion palpation or two-dimensional
      radiographic analysis.

PMID- 9567239
TI  - Treatment of symptomatic lumbar disc herniation using activator methods
      chiropractic technique.
AB  - OBJECTIVE: To describe a case of symptomatic lumbar disc herniation, successfully
      treated via chiropractic intervention using Activator Methods Chiropractic
      Technique. CLINICAL FEATURES: A 26-yr-old man suffered from a chronic
      multisymptom complex composed of low back pain, left groin pain, left leg pain,
      left foot drop and associated muscle weakness with atrophy. The symptoms had
      persisted for more than 2 yr after an athletic injury. Magnetic resonance imaging
      evaluation revealed a 6-mm focal central disc protrusion with accompanying
      deformation of the thecal sac, consistent with the presenting symptoms. Lumbar
      spinal surgery had been recommended to the patient as the appropriate medical
      management for optimal outcome. INTERVENTION AND OUTCOME: The patient elected to
      pursue chiropractic treatment in an effort to resolve his condition via
      conservative management. Chiropractic intervention consisted of mechanical-force,
      manually assisted short-lever adjusting procedures, rendered via an Activator
      Adjusting Instrument (AAI). The patient responded favorably and his multisymptom
      complex resolved within 90 days of treatment. No residuals or recurrences were
      noted at examination over 1 yr later. CONCLUSION: This report suggests that
      chiropractic treatment of lumbar disc disorders may be effectively implemented,
      in certain cases, via mechanical-force, manually assisted adjusting procedures
      using an AAI. We speculate that the use of an AAI, combined with Activator
      methods, may provide definitive benefits over side-posture manipulation of the
      lumbar spine in treatment of resistive disc lesions, because of the lack of
      torsional stress imposed upon the disc during instrumental spinal adjustment.
      Further study should be made in this regard to determine the safest and most
      effective method to treat lumbar disc lesions in a chiropractic setting.

PMID- 9567240
TI  - Management of a patient with calcium pyrophosphate deposition disease and
      meniscal tear of the knee: a case report.
AB  - OBJECTIVE: To describe the chiropractic management of a patient suffering from a
      right lateral meniscus tear concurrent with calcium pyrophosphate dihydrate
      (CPPD) deposition disease. CLINICAL FEATURES: A 51-yr-old bus driver suffered
      from right knee pain (7 on a 1-10 pain scale). The onset of the pain was gradual
      and increased during braking and accelerating. Palpatory tenderness was noted at
      the right lateral knee joint line and the inferior lateral margin of the patella.
      Active resistive range of motion (ROM) in the knee during extension was painful
      throughout the full ROM, whereas passive ROM was restricted in flexion at 110
      degrees. A positive McMurray's test reproduced pain at the knee. Radiographic
      analysis revealed CPPD deposition disease, and magnetic resonance imaging
      revealed a probable "parrot's beak" tear in the posterior horn of the right
      lateral meniscus. INTERVENTION AND OUTCOME: The patient was treated
      conservatively. He was instructed not to put weight on the knee and not to return
      to work for 5 days. Initial treatments involved the use of ice and interferential
      electrical stimulation along with glucosamine sulfate supplements. Bicycling,
      weight lifting for general fitness and general knee strengthening exercises were
      prescribed. Approximately 5 months after initial treatment, the patient was lost
      to follow-up; 12 months later, he returned for treatment because of a recurrence.
      Physical examination at that time revealed knee pain rated at 3/10 but there was
      no pain upon palpation, McMurray's test was negative and right knee ROM was full
      without pain. CONCLUSION: A patient suffering from CPPD can be managed by
      conservative means. The pathophysiology, clinical features and management
      considerations in the treatment of the patient's condition(s) are also discussed.

PMID- 9567241
TI  - Quantitative, qualitative and emergent approaches to chiropractic research: a
      philosophical background.

PMID- 9567243
TI  - An interactive model of chiropractic practice: reconstructing clinical reality.

PMID- 9567242
TI  - Normal response to large posteroanterior lumbar loads--a case study approach.

PMID- 9567244
TI  - X-ray of trunk rotation.

PMID- 9567245
TI  - Cancer reviews need to be systematic--but how?

PMID- 9567246
TI  - Consumption of tea and coffee and the risk of lung cancer in cigarette-smoking
      men: a case-control study in Uruguay.
AB  - This study investigated the effect of drinking tea or coffee on the lung cancer
      risk of male cigarette smokers in a case-control in Uruguay. Four hundred and
      twenty-seven lung cancer cases were frequency matched on age and residence with
      428 hospitalized controls suffering from conditions unrelated to tobacco smoking
      and diet. Whereas coffee drinking had no effect on the lung cancer risk of the
      cigarette-smoking men in this study, black tea consumption decreased this risk.
      Heavy drinkers of tea (two or more cups of tea per day) were associated with a
      reduced risk of 0.34 (95% CI 0.14-0.84). This protective effect was more evident
      among Kreyberg I tumors (squamous cell and small cell) and among light smokers.
      Possible sources of bias and mechanisms of action are discussed.

PMID- 9567247
TI  - The relevance of transforming growth factor beta 1 in pulmonary injury after
      radiation therapy.
AB  - The maximum dose of radiation which can be delivered to a tumor is limited by the
      tolerance of the surrounding normal tissues. The ability to identify patients at
      high or low risk of injury from radiation therapy might enable the clinician to
      tailor radiation doses in order to maximize efficacy and minimize risk. The
      cytokine transforming growth factor beta 1 (TGF beta 1) has been implicated in
      the development of normal tissue injury after irradiation in several organs,
      including the lung. Herein, the evidence supporting the role of TGF beta 1 in
      radiation-induced lung injury is reviewed. Using the treatment of non-small cell
      lung cancer as a model, we also discuss how it may be possible to identify
      patients at risk for this complication using measurements of plasma TGF beta 1,
      and how this information may be used in the future to adjust doses of radiation
      in the treatment of lung cancer.

PMID- 9567248
TI  - A randomized controlled trial of sulfamethoxazole/trimethoprim plus norfloxacin
      versus sulfamethoxazole/trimethoprim alone for the prophylaxis of bacteria
      infection during chemotherapy for lung cancer.
AB  - The efficacy of the prophylactic administration of sulfamethoxazole/trimethoprim
      (ST) plus norfloxacin (NFLX) versus ST alone to prevent the development of
      bacterial infection during chemotherapy-induced leukopenia was compared in
      patients with lung cancer. Patients who underwent systemic chemotherapy were
      randomized into one of the prophylactic regimens when grade 3 or 4 leukopenia
      occurred. Prophylactic treatment was performed on 133 courses of leukopenia in 75
      patients and the efficacy was evaluated on 127 of those courses after excluding
      those patients who demonstrated a fever within 24 h from the start of the
      prophylaxis. The number of patients who had leukopenia associated fever was two
      out of 63 (3.2%) with the ST plus NFLX regimen and 10 out of 64 (15.6%) with ST
      alone; the difference was statistically significant. The prophylactic use of ST
      plus NFLX was thus found to be more useful than ST alone for the treatment of
      chemotherapy-induced leukopenia in patients with lung cancer.

PMID- 9567249
TI  - Spontaneous biloma as a complication of small cell lung cancer.
AB  - Biloma is an extraductular collection of bile within a defined capsular space.
      Prior reports have documented an association between biloma and abdominal trauma,
      and between biloma and iatrogenic injury resulting from abdominal surgery,
      percutaneous catheter drainage, or transhepatic cholangiogram. To our knowledge,
      bilomas have not previously been associated with lung cancer. We report a case of
      spontaneous biloma that developed as a complication of small cell lung cancer.

PMID- 9567250
TI  - Synchronous double primary lung carcinomas associated with multiple atypical
      adenomatous hyperplasia.
AB  - A 71-year-old woman with synchronous bilateral primary lung carcinomas
      accompanied by multiple atypical adenomatous hyperplasias is described. The
      patient was found to have bilateral tumors during preoperative workup for the
      previously detected well differentiated adenocarcinoma of the right lung.
      Thoracoscopic wedge resection of the left upper lobe was performed to obtain a
      definitive diagnosis of the left lesion. Although intraoperative diagnosis was
      made by frozen section as atypical papillary lesion, postoperative diagnosis of
      this lesion was changed to well differentiated adenocarcinoma accompanied by
      surrounding atypical adenomatous hyperplasia (AAH). We diagnosed that the
      bilateral lesions were synchronous primary well differentiated adenocarcinomas
      independent to each other based on the criteria of Martini and Melamed and
      performed right upper and mediastinal lymph node dissection. The resected lobe
      contained not only the primary adenocarcinoma but also multiple small gray
      nodules which were diagnosed as AAHs. In summary, it was diagnosed that the
      patient had synchronous double primary lung adenocarcinomas of T1 N0 M0
      pathological stage and 12 solitary atypical adenomatous hyperplasias. The patient
      is doing well with no signs of recurrence 24 months after the operation. This
      case might be an example of the adenoma-carcinoma sequence of lung cancer. A
      careful follow-up study is mandatory for this patient with special regard to the
      further development of lung carcinoma in the future.

PMID- 9567251
TI  - Maintenance chemotherapy for small cell lung cancer: a critical review of the
      literature.
AB  - Maintenance chemotherapy after induction therapy is a controversial topic in
      small cell lung cancer. We carried out a critical review of the literature on
      this topic. Since 1980, 13 randomized trials have been published. One shows a
      statistically significant difference in survival in favor of maintenance, five
      obtain some survival advantages in subgroups of patients, one shows a
      significantly shorter survival with maintenance and in six studies, there is no
      difference between both arms. A quantitative overview or meta-analysis was
      unpracticable because of the lack of data for calculation of the odds ratio in
      the publications and because of the heterogeneity of the studies' designs. A
      qualitative overview was carried out using two scales: the Chalmers scores and
      the European Lung Cancer Working Party (ELCWP) score. Correlation between both
      scores was excellent. There was no significant difference in quality scores with
      both methods between negative trials and those who showed some survival advantage
      for survival. The overall quality of the publications was not good, with
      important methodological aspects missing, such as a clear definition of the
      primary objective or an a priori estimate of the sample size necessary to conduct
      the trial. We concluded that maintenance chemotherapy could have some indications
      and that good quality trials, as reflected by very high quality scores, need to
      be carried out in the future.

PMID- 9567252
TI  - Various clinical entities of bronchogenic adenocarcinoma.

PMID- 9567253
TI  - [Virologic analysis of 1,000 blood samples processed for cytomegalovirus
      isolation (viremia) and pp65 antigenemia in immunodepressed patients].
AB  - BACKGROUND: To study the principal virological aspects of 1,000 blood samples
      processed for cytomegalovirus (CMV) isolation (viremia) and pp65 antigenemia
      assay in immunosuppressed patients, and to compare the diagnostic efficacy of
      both technics. PATIENTS AND METHODS: All the blood samples collected with EDTA,
      were fraccionated by dextran sedimentation. The polymorfonuclear rich fraction
      was used for the isolation of CMV by the shell-vial cell culture and the pp65
      antigenemia assay. The cell cultures were stained at 18-24 hours with a
      monoclonal antibody against p72 CMV antigen. RESULTS: The 1,000 blood samples
      studied belonged to 363 patients (299 infected by the HIV, 49 renal transplant
      recipients, and 15 patients with haematologic diseases). 78 patients (21.4%)
      developed a CMV infection and/or disease. The overall results obtained in the
      comparative study for the CMV detection in peripheral blood were 86.7% for the
      antigenemia assay and 58.5% for the shell-vial culture (p = 0.0001). Of 49
      patients with renal transplant, 20 (40.8%) presented with a CMV infection versus
      19.3% in the HIV-positive group. The transplant recipient patients presented most
      frequently positivity for both diagnostic technics, and the HIV-positive patients
      a higher percentage of antigenemia-positive with culture negative. The shell-vial
      culture (viremia) had most diagnostic efficacy in the transplant recipients
      group. CONCLUSIONS: In the immunosuppressed patients the pp65 antigenemia assay
      has demonstrated a high diagnostic efficacy for CMV detection in peripheral
      blood. However because the antigenemia not always correlates with a replicative
      viral load, it is necessary to routinely perform culture of the blood in a cell
      culture system, preferently by the shell-vial method, because this system allows
      to make the diagnosis of CMV infection in a short period of time.

PMID- 9567254
TI  - [Usefulness of preoperative location studies in the initial surgical intervention
      in primary hyperparathyroidism].
AB  - BACKGROUND: The aim of the study was to assess whether preoperative localization
      is helpful in improving the outcome of initial surgery of primary
      hyperparathyroidism (PHPT). PATIENTS AND METHODS: Retrospective review of 100
      patients treated surgically for PHPT. In 30 cases (group I) 3 or 4 localization
      studies were performed from the following: ultrasonography (US), computed
      tomography (CT), thallium-technetium substraction scintigraphy (TTS), and
      technetium 99m-sestamibi scanning (MIBI). Thirty one patients (group II) were
      operated without previous localization. Sensitivity and false localization rate
      of image studies were calculated, and cure and surgical complication rates were
      compared in both groups. RESULTS: Both groups were similar in mean age (56.2 vs
      52.2 years), serum calcium (12.3 vs 12.1 mg/dl), intact PTH levels (304 vs 254
      pg/ml), pathology (26 adenomas, 3 hyperplasias and 1 carcinoma vs 27 adenomas, 3
      hyperplasias and 1 carcinoma) and additional clinical and biochemical data. The
      highest sensitivity technique was for MIBI (62.5%). The highest false
      localization rate was for CT (27.6%). No significative differences were found
      between groups I and II for the cure rate (90% vs 87.1%) or surgical
      complications (3.3% vs 3.2%). CONCLUSIONS: In our series of patients with primary
      hyperparathyroidism preoperative localization studies display low sensitivity and
      estimable false localization rate. These techniques increment cost and don't
      improve success rate of initial surgery in PHPT. Therefore, we believe its
      performance controversial.

PMID- 9567256
TI  - [Role of endothelial cells in the biological cycle of human cytomegalovirus].

PMID- 9567255
TI  - [Site of care provision, etiology and treatment of community-acquired pneumonia
      in Palma de Mallorca].
AB  - BACKGROUND: It is not common that community-acquired pneumonias studies include
      patients non treated in hospital. The objectives were: to determine the cases
      managed in the ambulatory setting; to describe the clinical features; to identify
      the aetiological agents, and to describe the treatment, comparing inpatients with
      outpatients. PATIENTS AND METHODS: Observational prospective study. Population
      attended at three teaching primary care centers of Palma de Mallorca (60,450
      habitants). Patients (> 14 years) were investigated when diagnosticated of
      community-acquired pneumoniae, from November 1992 to December 1994. Exclussions:
      HIV infection, patients living in a nursing home and tuberculosis. Data were
      collected in both Hospital and primary health care centers. Epidemiological,
      clinical, radiological and laboratory findings were recorded at the initial visit
      and 21 days after. RESULTS: 91 cases were investigated. 57% were managed at the
      primary care centers exclusively, 63.3% of the patients who went initially to the
      hospital were admitted in; but only 10.9% of those who went initially to the
      primary care centers (p < 0.005). 24 patients were hospitalized. 56
      microbiological agents were identified in 48 patients (52.7%): Mycoplasma
      pneumoniae (10); Streptococcus pneumoniae (9); Influenza B (8); Chlamydia
      psittacci (7); Influenza A (7); Coxiella burnetii (5); Chlamydia pneumoniae (4);
      Legionella (3); Adenovirus (2); and Parainfluenza 3 (1). Mycoplasma was
      predominant in outpatients: 9 cases. S. pneumoniae in inpatients: 5 cases.
      Eritromycin was the most common treatment prescribed (76.9% of patients), alone
      or in combination with other antibiotics. Monotherapy was most common at primary
      care yield (96.7%) than at the hospital (45.2%) (p < 0.005). CONCLUSIONS: Most of
      the patients with community-acquired pneumonias are managed at primary health
      care centers. M. pneumoniae is the predominant microbiological agent in
      outpatients and S. pneumoniae in inpatients. Erithromycin is the most used
      antibiotic in both groups of patients.

PMID- 9567257
TI  - [Detection of predisposition to cancer: a solution or a problem?].

PMID- 9567258
TI  - [Familial hypercholesterolemia: molecular identification and characterization of
      the first compound homozygote in Spain].
AB  - Homozygous familial hypercholestrolemia (FH) is a rare genetic disorder (one in 1
      million persons) due to two different mutations in the LDL receptor gene
      (compound homozygous) or, rarely, to the presence of the same mutation in the two
      aleles. In these patients the absence of a functional LDL receptor produces
      extreme elevations of plasma cholesterol levels that need an aggressive and
      expensive treatment with LDL apheresis or hepatic transplantation. The clinical
      evolution is poor with early coronary heart disease. Molecular biology techniques
      allow a genetic diagnosis and a genetic counseling in the affected subjects. We
      have identified and characterized the first compound homozygous of FH in Spain
      using the single strand conformational polymorphism (SSCP) analysis. The patient
      is a 30 years old female, who carried two different mutations in the LDL receptor
      gene: the G528V and the D280G (a new mutation). These mutations produce
      significant changes in the aminoacid sequence and could be classified as class 2.

PMID- 9567259
TI  - [Factors influencing economic cost of home oxygen therapy].

PMID- 9567260
TI  - [Role of nutrition in chronic obstructive pulmonary disease].

PMID- 9567261
TI  - [Toxic psychosis as unusual presentation of body packer syndrome].

PMID- 9567262
TI  - [Gastric disease caused by Helicobacter pylori: recent advances in treatment].

PMID- 9567263
TI  - [Prevalence of obesity in the Valencian community].

PMID- 9567264
TI  - [Association between C virus infection and anticardiolipin antibodies].

PMID- 9567265
TI  - [Cardiovascular mortality in Spain and its autonomous communities (1975-1992)].
AB  - BACKGROUND: Given the great relevancy of the cardiovascular diseases, were
      analyzed the cardiovascular mortality in the Spanish autonomous communities and
      its trend during the period 1975-1992, to identify communities with a high death
      risk by these diseases and to as certain the underlying factors. MATERIAL AND
      METHODS: The mortality rates standardized by age are calculated for the diseases
      of the circulatory system (DCS), ischaemic heart disease (IHD) and
      cerebrovascular disease (CVD). The mortality trend has been quantified through
      the percentual change annual means, using a log-lineal model. RESULTS: The
      Communities of Valencia, Extremadura, Andalusia and Murcia show the highest
      cardiovascular diseases mortality rates while the Communities of Madrid, Navarra,
      Castilla and Leon and Aragon present the most decreases. In all the communities a
      decrease of the mortality by DCS has occurred, that ranges from a percentual
      decrease annual means higher than 3% in Navarre (-3.7%) and Madrid (-3.4%) to
      values that they do not reach to the 2% of decrease in Murcia (-1.8%) and
      Balearic Islands (-1.9%). In males as well as in females, the mortality by IHD
      and CVD falls in all the communities in the period 1975-1992, though the decrease
      is much greater for CVD. CONCLUSIONS: This study demonstrates a consistent fall
      of the cardiovascular mortality in all the Spanish autonomous communities and
      some considerable differences in the level and in the trends of the magnitude
      mortality among these communities during all the studied period.

PMID- 9567266
TI  - [Smoking initiation in students: cross-sectional and longitudinal study of
      predictive factors].
AB  - BACKGROUND: This study examines the evolution of tobacco use among schoolchildren
      in sixth and seventh grades in Barcelona (11-13 years) and identifies smoking
      risk factors through cross-sectional and follow-up analysis. POBLATION AND
      METHODS: The cohort consists of 1,003 students attending 13 schools who served as
      control units for a study assessing the effects of a school-based addictive
      substances prevention program. Participants answered the same questionnaire in
      1990 and 1991. Risk factors for the experimentation and for regular smoking are
      studied through cross-sectional and prospective studies. RESULT: In a year,
      smokers increase from 9.7% to 18.9% and regular smokers rise from 1.1% to 5.5%.
      The initial cross-sectional analysis finds stronger associations than the follow
      up one. Some variables loose their significance in the longitudinal analysis.
      Among non-smokers, the strongest predictors to emerge are intention to smoke, the
      belief that smoking is fun, peers, siblings and mother consumption, and being
      male; however girls appear to consolidate the consumption more than boys among
      the cohort of triers. CONCLUSIONS: Tobacco use prevalences are consistent with
      other studies developed in our city. Social environment emerges as an important
      predictor; friends, siblings and mothers tobacco use and gender are the main risk
      factors.

PMID- 9567267
TI  - [Genetic research on Usher's syndrome in Spain].

PMID- 9567268
TI  - [Role of angiotensin II as blood pressure regulator and the the development of
      lesions in hypertension target organs].

PMID- 9567269
TI  - [Clinical and biochemical characteristics of a new case of Tangier disease in
      Spain].
AB  - Tangier disease (TD) is a rare autosomal recessively inherited disorder
      characterized by the absence or severe deficiency of high density lipoproteins
      (HDL) in plasma. The affected subjects have no HDL subfraction alpha-Lp A-I,
      which is the most important subfraction in normal HDL, and can not transform
      prebeta-Lp A-I subfraction in alpha-Lp A-I. In this article we describe the
      second homozygous patient for TD in Spain, who presented the typical clinical and
      biological features (hypocholesterolemia with the absence of plasmatic HDL
      cholesterol, hepatosplenomegaly and orange yellow tonsils) and the alterations in
      HDL subfractions.

PMID- 9567270
TI  - [Obesity and socioeconomic status].

PMID- 9567271
TI  - [Primary heart tumors. Study of 21 cases].

PMID- 9567273
TI  - [Quantification of blood levels of tryptase in the diagnosis of anaphylaxis].

PMID- 9567272
TI  - [Acute nephrotoxicity resolved by cyclosporine A, induced by simultaneous
      administration of colchicine].

PMID- 9567274
TI  - [Availability of clinical laboratories for the assessment of cardiovascular risk
      in Catalonia].

PMID- 9567275
TI  - [Bacteremia in non-hospitalized patients].

PMID- 9567276
TI  - [Campaign for the detection of minor beta-thalassemia and prevention of major
      beta-thalassemia in the isle of Menorca. 10-year experience].
AB  - BACKGROUND: The high prevalence of betathalassemia minor and the presence of
      several cases of thalassemia major in Menorca (Spain) led us, ten years ago, to
      set up a population based prevention campaign, following the basic schedule of
      those already taking place in other areas, specially in Italy. PATIENTS AND
      METHODS: The target population was the children in the last year of mandatory
      school, when they are 13 to 14 years old. The campaign started in the school year
      1986-1987 and in the 1995-1996 course we reached the tenth yearly campaign. The
      campaign was structured in three stages: the first one included all information
      and educational aspects; the second step corresponded to blood sampling and
      detection of carriers; finally, results were reported to the individuals and
      genetic counseling was given. For evaluation purposes, we have monitored
      participation rates, the proportion of detected carriers which present to
      haematology visit and the trend in the proportion of carriers which previously
      knew their status. RESULTS: A total of 8,591 children were screened, accounting
      for a 83.8% participation rate. The observed prevalence was 26.7/1000 (95% CI,
      23.5-29.9/1000). We also detected 9 cases of alfathalassemia and 4 cases of
      deltabetathalassemia. CONCLUSIONS: Our results show that participation rates may
      be reached through school screening campaigns for thalassemia. After ten years of
      campaign, the number of not previously known cases has become small, indicating
      that the campaign screening to relatives of detected carriers and a higher
      consciousness level in the general population have given the expected effect. In
      the last 14 years, not a single homozigote case has been born, although we cannot
      conclude that this has been only due to the campaign.

PMID- 9567277
TI  - [Content of carbohydrates and trace elements in a group of non-alcoholic drinks].
AB  - BACKGROUND: In order to elaborate recommendations for the dietetic care of
      diabetic patients and other clinical disorders we have measured the concentration
      of carbohydrates and trace elements in a group of non alcoholic refreshments of
      current use in Spain. MATERIAL AND METHODS: Thirty refreshments were classified
      into 10 groups. Glucose and phosphate were measured by hexokinase and reduction
      of phospho-molybdate methods respectively in an autoanalyzer Dax-72. Glucose and
      fructose were analyzed by cellulose thin-layer chromatography; glucose, fructose
      and sucrose by gas chromatographys. Sodium and potassium by emission
      spectrophotometry and calcium, magnesium, iron, copper and zinc by atomic
      absorption spectrophotometry. RESULTS: Light refreshments and soft drinks have no
      carbohydrates. Isotonic beverages, fruit juices, cool tea and non alcoholic beers
      had less than 10 g/dl. Tonic waters, Fanta, different coles, non alcoholic bitter
      and others had more than 10 g/dl. Sodium levels between 15-20 mEq/l were found in
      the isotonic beverages and 7-Up and levels of 7 mEq/l in the others. Potassium
      values between 15-40 mEq/l were found in the fruit juices, 3-4 mEq/l in Gatorade
      and less than 1 mEq/l in the others. CONCLUSIONS: Light refreshments and soft
      drinks contain low concentrations of carbohydrates and sodium. Fruit juices have
      high potassium concentration. Such information can be especially useful for
      dietetic care of diabetic patients.

PMID- 9567279
TI  - [Beta-thalassemia, 1998].

PMID- 9567280
TI  - [Protease inhibitors of the human immunodeficiency virus].

PMID- 9567278
TI  - [Breast cancer and heredity: results of a population case-control study in
      Girona].
AB  - BACKGROUND: To characterise the relationship between breast cancer and different
      aspects of the reproductive life, use of drugs and alcohol by family history of
      breast cancer. PATIENTS AND METHODS: From the cancer registry of Girona, Spain,
      330 women were identified with histologically confirmed breast cancer during 1986
      1989. For each case, a control woman was selected from a random sample of the
      population living in the matched area to the case by age (+/- 5 yr.). The
      information was collected by a personal interview and included: family history of
      breast cancer, reproductive history, presence of acne during the teenage years,
      use of oral contraceptives and drugs for sleep and anxiety disorders, and alcohol
      consumption. RESULTS: 18.5% of breast cancer cases and 8.9% of all controls had a
      family history of breast cancer. Family history on a first degree relative
      (mother or sister) was present in 10.6% of the cases and 2.8% of controls, which
      represented an odds ratio for breast cancer of 3.7 (95% CI, 1.8-7.8) higher than
      the general population. Women with a first degree family history of breast cancer
      were at higher risk for breast cancer if they had a history of acne during the
      teenage period (OR = 2.4; 95% CI, 1.1-5.2) and if they referred long menstrual
      periods in the early years of menarche (OR = 3.1; 95% CI, 1.3-7.0). Women with no
      family history had a higher breast cancer risk if they had a late menarche, long
      menstrual periods, late first full term pregnancy, and history of acne during
      puberty. Alcohol consumption and use of drugs for anxiety and sleep disorders
      were associated with a decreased risk of breast cancer. CONCLUSIONS: First degree
      family history of breast cancer seems to be the best risk indicator for
      developing breast cancer. Long menstrual periods and presence of acne during
      puberty may indicate hormonal imbalance that act independently of the family
      history in breast cancer development.

PMID- 9567281
TI  - [Diagnostic usefulness of glutamic acid decarboxylase antibodies in stiff-man
      syndrome].
AB  - Stiff-man syndrome (SMS) is a rare neurological disorder characterized by
      progressive rigidity of the axial musculature with superimposed spasms.
      Frequently, SMS remains undiagnosed for prolonged periods or the patients are
      diagnosed of a primary psychiatric disorder. 60% of the SMS patients harbor GAD
      autoantibodies (GAD-Ab). We have analyzed the diagnostic value of GAD-Ab in a
      syndrome whose clinical expression is not well known, but its diagnosis is
      performed by clinical criteria. Five patients were studied following the
      established clinical criteria for diagnosis of SMS. GAD-Ab were analyzed by
      radioimmunoassay (RIA) and immunohistochemistry, and confirmed by immunoblot. The
      GAD-Ab titers were compared with those of 49 patients with insulin-dependent
      diabetes mellitus (IDDM), 322 with other neurological disorders, 14 non-IDDM
      first-degree relatives of IDDM patients with antibodies anti-islet cells and 91
      normal subjects. Three patients fulfilled all clinical criteria (typical SMS).
      Unilateral limb symptoms alone, and acute onset with rapid progression involving
      the distal limb muscles constituted the atypical features of SMS in the remaining
      2 patients. The 5 patients presented several serum organ-specific autoantibodies.
      All but one also presented autoimmune diseases. By RIA, GAD-Ab titers from all
      patients were elevated (mean: 24,532 +/- 26,892 U/ml) and significantly higher
      than the titers of IDDM patients without neurological disorders (mean: 48 +/- 112
      U/ml) (p < 0.0001). GAD-Ab were absent in the non-SMS patients and in normal
      subjects. These findings suggest that clinical expression of SMS is more
      extensive than that recognized by the established criteria. GAD-Ab are helpful to
      define the clinical spectrum of SMS.

PMID- 9567282
TI  - [Variations in medical practice: importance, causes, and implications].

PMID- 9567283
TI  - [The future of tuberculosis prevention].

PMID- 9567284
TI  - [Characteristics of psychiatric patients seeking medical advice].

PMID- 9567285
TI  - [Pulmonary hemorrhage and thrombolysis].

PMID- 9567286
TI  - [Rationale for hospital emergencies].

PMID- 9567287
TI  - [Soft and depressive abdomen].

PMID- 9567288
TI  - [The good use of medicinal plants].

PMID- 9567289
TI  - [Apolipoprotein E and response to statins].

PMID- 9567290
TI  - [Restriction endonuclease Sse9I from Sporosarcina sp. strain 9D recognizes the 5'
      AATT-3' DNA sequence].
AB  - A new restriction endonuclease Sse9I was isolated from the bacterial strain
      Sporosarcina sp. 9D. The enzyme belongs to Type II restrictases and recognizes
      the tetranucleotide sequence 5'-AATT-3'. The enzyme cleaves DNA before the first
      adenine residue, so it is a true isoschizomer of Tsp509I restrictase. However,
      unlike the prototype, Sse9I digests DNA at 55 degrees C and loses its activity
      after 20 min storage at 65 degrees C.

PMID- 9567291
TI  - [Coimmobilization of proteolytic and bacteriolytic enzymes and properties of
      isolated materials].
AB  - Coimmobilization of proteolytic and bacteriolytic enzymes on a carboxyl
      containing grafted cellulose copolymer was studied. The resistance of lysozyme to
      gamma-sterilization significantly increased after coimmobilization with a
      proteolytic enzyme. The resulting material accelerated the cleansing of wounds.

PMID- 9567292
TI  - [The effect of physical and chemical environmental factors on the growth of
      Pseudomonas aeruginosa dissociants].
AB  - The growth rates of the R-, S-, and M-dissociants of a hydrocarbon oxidizing
      strain of Pseudomonas aeruginosa were comparatively studied under variable
      environmental conditions (aeration, temperature, pH, UV radiation, and
      concentration of NaCl). The R-dissociant was found to be more tolerant to UV
      radiation, high aeration, and temperature. The S-dissociant, which is the most
      effective in degrading hydrocarbons, gains a selection advantage under acidic
      conditions. The M-dissociant has advantages over the other dissociants under
      conditions of decreased aeration, low temperature, and high concentration of
      NaCl. The results of this work are important for optimizing microbial growth
      conditions and for identification of bacteria. Probably, the biological sense of
      dissociation is to broaden the boundaries within which a species can survive
      under changeable environmental conditions.

PMID- 9567293
TI  - [Study of cytokinins produced by rhizospheric microorganisms].
AB  - A high-molecular-weight complex of a polysaccharide and biologically active
      cytokinins was found in the culture liquid of rhizosphere microorganisms of the
      genus Bacillus. Enzyme immunoassay and thin-layer chromatography showed that
      zeatin riboside and a hormone nucleotide were the main cytokinins observed.
      Components of this complex were linked by a noncovalent bond.

PMID- 9567294
TI  - [Element composition of bacterial cells of various taxa].
AB  - The elemental compositions of cells of representatives of five bacterial genera
      (Hyphomonas vulgare NP-160, Caulobacter bacteroides NP-105, Flectobacillus major
      Mm, Escherichia coli, and Spirulina platensis) was studied by electron
      microscopic x-ray microanalysis. The contents of P, S, Cl, K, and Ca were
      determined. The bacterial species studied in this work substantially differ by
      the contents of these elements. A high content of K is typical of S. platensis,
      whereas F. major, an aquatic form, is rich in Cl. The other bacterial species
      were had the levels of K, Ca, and the K/Ca index, which correlated with the
      stability of their cell membranes and resistance to stress. In E. coli, the
      spectrum of the elemental composition and the values of P/S and K/Ca are
      indicative of high energy potential and low tolerance of membranes.

PMID- 9567295
TI  - [Relationship between the structure and antioxidant activity of various
      betalains].
AB  - Antioxidant activities of nine betalains were studied on the model of linetol
      peroxidation. Betaxanthins were shown to have the highest antioxidant activity.
      The relationship between the chemical structure and antioxidant activity of
      betalains was examined.

PMID- 9567296
TI  - [Analysis of B-epitopes formed on proteins after treatment with glutaraldehyde].
AB  - Structural analysis of the B-epitopes formed on protein macromolecules by
      glutaraldehyde treatment with subsequent block of free active groups by glycine
      was performed. Two types of antigenic determinants recognized by different
      antibody populations were found by protein chemistry and immunochemistry
      techniques. An efficient method of blocking the antibodies to the epitopes formed
      on proteins by glutaraldehyde was developed.

PMID- 9567297
TI  - [A novel use of cholinesterase amperometric biosensor for selective determination
      of 2,4-dichlorophenoxyacetic acid].
AB  - A new method of detection of 2,4-dichlorophenoxyacetic acid by means of
      immobilized monoclonal antibodies and an amperometric cholinesterase biosensor is
      proposed. A combination of monoclonal antibodies to 2,4-dichlorophenoxyacetic
      acid with an enzyme electrode provides high selectivity of measurements and
      allows trace amounts of this pesticide to be detected within a concentration
      range of 1 x 10(-1) to 5 x 10(-7) M with a sensitivity threshold of 5 x 10(-12)
      M.

PMID- 9567298
TI  - [Model for the organizational structure of the Regional Service for Animal
      Health].
AB  - The organisational structure of any unit must be a reflection of the way in which
      work is distributed and of specialisation in the constituent parts. Co-ordination
      between these parts requires the establishment of standards, strategies,
      procedures and official controls, as well as a chain of command, in order to
      attain the desired objectives. The authors present an alternative model for
      designing an organisational structure for district Veterinary Services of a given
      country. This model will assist the establishment of basic criteria for
      evaluating such Services, facilitating their integration into the procedure for
      planning animal health activities, and providing a better comprehension of their
      function within the livestock sector.

PMID- 9567299
TI  - Veterinary ethics in the liberalized market: the Zambian environment.
AB  - The Zambian veterinary delivery system is responding to changes in the socio
      economic environment and in the structural organisation and functions of the
      delivery system itself. Privatisation and liberalization are now being actively
      pursued as official Government policy with free competition being encouraged. As
      a profession, veterinarians must safeguard their interests by, among other
      actions, self-regulating their activities so as to enhance their standing in
      society and to develop or maintain standards worthy of the profession. This will
      be achieved largely through the Veterinary Association of Zambia. It is also
      imperative for the Government to ensure that governmental policy succeeds by
      providing an appropriate environment and by protecting the public and animals
      from undesirable actions by agents of the delivery system (veterinarians and para
      professionals). There is also the need to maintain harmony among these agents and
      to resolve any differences which develop between colleagues and subordinates.
      Such objectives call for laws and codes of ethics appropriate to the environment
      of Zambia to be established to guide practitioners, the Veterinary Association,
      the public and any statutory body which is established to enforce these laws and
      codes of conduct. The authors explore the meanings of ethics and laws, the
      principles which will guide stakeholders to develop such ethics and the roles of
      veterinary associations, statutory bodies, e.g. Veterinary Boards or Councils,
      veterinary schools and other stakeholders, such as para-professionals, including
      auxiliaries. The authors also examine the implications of certain rules, such as
      free competition in service delivery. The establishment of regulations and
      quality control methods are discussed briefly.

PMID- 9567300
TI  - A proposed classification of veterinary epidemiosurveillance networks.
AB  - With the signing of the General Agreement on Tariffs and Trade and the
      establishment of the World Trade Organisation, the trading environment for animal
      products has changed. Disease control measures can no longer be applied as trade
      barriers unless supported by scientific epidemiological data. In this context, it
      has become necessary, if not obligatory, to gain accurate and up-to-date
      knowledge about the epidemiological status of important infectious animal
      diseases. The role of veterinary epidemiosurveillance networks is therefore
      gaining importance. Furthermore, epidemiosurveillance contributes to the
      protection of animal populations from exotic or emerging diseases, as well as to
      the development and evaluation of disease control programmes. Despite the large
      diversity of surveillance networks, the authors propose a method of network
      classification. The criteria for classification are as follows: the type of
      disease being monitored (i.e., surveillance of exotic versus endemic diseases).
      The number of diseases concerned (i.e., focused networks versus broad-based
      networks). The area being covered (i.e., local, national or international
      networks). The population being monitored (i.e., whether the network is targeted
      at suspect or susceptible animals). The sampling strategy of the network (i.e.,
      sample-based networks versus exhaustive networks). The method of collecting data
      (i.e., passive data collection versus active collection). The type of network
      management (i.e., autonomous management versus that which is integrated with
      other programmes). This classification is discussed and illustrated by examples
      published in the literature. It may aid in the future development of a grid for
      the evaluation of veterinary epidemiosurveillance networks.

PMID- 9567301
TI  - [Network for epidemiologic surveillance of animal diseases in Chad].
AB  - An epidemiosurveillance network for diseases of animals was introduced in Chad to
      ensure early reporting to animal husbandry organisations should the incidence of
      an existing disease increase, or should an exotic disease reappear. The network
      also serves for the collection of information on the principal diseases of
      livestock. A list of eight priority diseases was drawn up with specific
      surveillance objectives for each disease. Information (from surveys and sampling)
      from all new outbreaks of the diseases under surveillance is gathered by
      participants in the field (officials in public service and private veterinarians)
      and sent to the diagnostic laboratory, which examines the findings before
      disseminating them to the field. The first year of operation in the field has
      made it possible to evaluate the feasibility of the method and to collect
      fundamental epidemiological information on the diseases under surveillance. The
      advantage of the network is the provision of a means of communication between the
      field and the laboratory. The network enables collection of information in a
      standard form, the training of field agents and the organisation of the structure
      of the laboratory. Persistent problems are the motivation of some participants in
      the field and difficulties in communication which have to be overcome in order to
      obtain reliable data rapidly.

PMID- 9567302
TI  - National surveillance of poultry diseases in Lebanon.
AB  - From 1992 to mid-1996, a national survey of poultry diseases in Lebanon was
      conducted. This surveillance included meat breeder, layer breeder, commercial
      layer and chicken broiler flocks. The history, signs, lesions and laboratory
      tests of poultry were used in the diagnosis of prevalent poultry diseases.
      Culture techniques were used to screen for bacterial diseases; serological
      techniques and, to a lesser extent, culture techniques were used to diagnose
      viral diseases; and both serological and culture techniques were used to diagnose
      Mycoplasma infections. The outbreaks of diseases detected in broiler breeder
      flocks and the number of such flocks experiencing these diseases were as follows:
      femoral head necrosis (6), egg-drop syndrome (3), reovirus-associated
      malabsorption syndrome (3), synovitis (Mycoplasma synoviae infection) (7),
      swollen head syndrome (SHS) (3), tenosynovitis (viral arthritis) (1), lymphoid
      leukosis (3), avian encephalomyelitis (1), fowl pox (1) and aortic rupture (1).
      The disease outbreaks detected in layer breeders were as follows: SHS (2), bumble
      foot (2), egg-drop syndrome (3) and avian infectious bronchitis (IB) (1). The
      disease outbreaks detected in commercial layer flocks were as follows: egg-drop
      syndrome (5), avian infectious laryngotracheitis (2), avian IB (nephrogenic
      strain) (1), malabsorption (1), avian tuberculosis (Mycobacterium avium) (1),
      Marek's disease (1), fowl pox (1), Salmonella enterica subsp. enterica
      Enteritidis infection (1), salpingitis (1) and Heterakis gallinae infestation
      (1). The disease outbreaks detected in broiler flocks were as follows:
      colibacillosis (40), infectious bursal disease (Gumboro disease) (15),
      malabsorption syndrome (8), avian infectious laryngotracheitis (8), paratyphoids
      (salmonellosis) (7), femoral head necrosis (8), SHS (6), avian mycoplasmosis
      (Mycoplasma gallisepticum infection) (6), synovitis (7), avian IB (6), botulism
      (1), avian encephalomyelitis (1) and gangrenous dermatitis (1). Diseases which
      occurred and which were reported for the first time in Lebanon were as follows:
      bumble foot, femoral head necrosis, avian IB (nephrogenic strain), malabsorption
      syndrome and SHS. This surveillance helped to establish baseline data concerning
      the predominant poultry diseases in Lebanon. Such information is a prerequisite
      for future regional and international collaboration to identify the source of the
      aetiological agents and to control their spread to neighbouring countries.

PMID- 9567303
TI  - Preliminary seromonitoring of rinderpest among cattle raised under different
      husbandry systems in Saudi Arabia.
AB  - Using the competitive enzyme-linked immunosorbent assay for the seromonitoring of
      rinderpest in Saudi Arabia, antibodies were detected in 30% of the sera of 1,018
      cattle slaughtered at Riyadh abattoir during June and July 1995. The correlation
      between the detection of antibodies and the origins of the slaughtered animals
      was analysed. All the culled dairy cows had detectable antibodies. The
      proportions of bulls giving serologically positive results were as follows: 57%
      for animals imported from rinderpest-free countries and vaccinated upon arrival
      in Saudi quarantine, 20% for native breeding animals and 17% for five- to ten
      month-old bull calves born on commercial dairy farms and then raised on separate
      feedlot farms. In addition, of 105 native cattle sacrificed during the Hajj
      season in May 1994, 77% had antibodies against rinderpest virus. On the other
      hand, testing of 17 groups of dairy heifers (from 1 week to 24 months of age),
      born to immune dams and vaccinated against rinderpest at the ages of six and ten
      months, revealed the absence of detectable antibodies in the sera of some animals
      which were between two and ten months of age. Results are interpreted in relation
      to evaluation of the continuing vaccination programmes and their efficacy as an
      element of the national programme for the control of rinderpest.

PMID- 9567304
TI  - [Seroepidemiologic indicators for the evaluation of campaigns for the control of
      foot-and-mouth disease].
AB  - A sero-epidemiological survey was conducted in two districts in Argentina between
      1993 and 1995, to provide additional information on the epidemiology of foot and
      mouth disease (FMD) in Argentina and to assess the level of immunity in cattle
      populations, and the circulation of FMD virus. As part of the final stage of this
      survey, a comparison was made of the results obtained by the enzyme-linked
      immunosorbent assay (ELISA) and agar gel immunodiffusion techniques. Levels of
      population immunity against the four types of virus included in the vaccine
      increased progressively during the period of the survey until, in 1995, at the
      end of the vaccination period, the percentage of animals possessing adequate
      levels of protection was approximately 77% in yearlings, and more than 94% in
      cattle over one year old. During the three-year study, there was a clear tendency
      for viral activity to diminish, until in 1995 when between 3% and 0.6% were
      positive to the agar gel immunodiffusion test for the antigen associated with
      viral infection. By contrast, the ELISA detected antibody in about five times as
      many animals. The authors show how the increase in the level of population
      immunity was accompanied by a fall in viral activity.

PMID- 9567305
TI  - Computerised methods for animal health risk assessment using the EPIZOO 2.6
      program.
AB  - A computerised set of methods for the risk assessment of infectious diseases has
      been developed as part of a software package which deals with animal population
      health and disease analyses and programming (EPIZOO, version 2.6). This set
      includes methods for calculating the following: general indicators of risk of
      animal disease. Risk probability assessment of propagation of disease. Risk
      probability assessment of the introduction of disease through the importation of
      animals and their products, based on predefined criteria and on non-predefined
      criteria. Risk comparison of the introduction of one disease agent from several
      territories. Risk comparison of the introduction of several disease agents from
      one territory. Risk of disease propagation related to the movement and
      concentration of the animal population. Risk of disease propagation related to
      the transfer of animal products. Risk of the probability of negative test results
      in infected animals. Risk of the probability that at least one imported animal or
      animal product unit is infected.

PMID- 9567306
TI  - Risk assessment and risk regionalization, based on the surveillance system for
      foot and mouth disease in South America.
AB  - Within the framework of the International Animal Health Code of the Office
      International des Epizooties (OIE), important contributions have been made by the
      Animal and Plant Health Inspection Service/United States Department of
      Agriculture (APHIS/USDA), the Ministry of Agriculture of Canada, the Ministry of
      Agriculture and Fisheries of New Zealand and other organisations, by the
      development of risk assessment methods and regionalization criteria for risk
      assessment. The authors attempt to contribute to these efforts by proposing a
      regional risk evaluation of foot and mouth disease (FMD) in South America. Two
      examples of risk assessments for international trade, i.e., in bovine embryos and
      in meat, are used to demonstrate the importance of an effective disease
      surveillance system as the basis for risk regionalization for international trade
      in animals and animal products. As a result of progress in the control and
      eradication of FMD in South America, it is expected that major livestock
      production regions will soon be in low- to very low-risk categories.

PMID- 9567307
TI  - [International and regional standardization of immunoenzyme tests: methods,
      concerns and limitations].
AB  - Numerous attempts have been made to standardise immuno-enzyme techniques (enzyme
      linked immunosorbent assay: ELISA) used for the diagnosis of infectious diseases,
      in order to improve the reproducibility of the tests, expression of results,
      choice of a positive threshold, and selection of reference samples. The
      international standardisation of reagents and test protocols appears essential
      for quality control and the comparison of results between laboratories, but the
      interpretation of results can encounter major differences depending on the
      geographical sector under study. Based on these studies, and in the light of a
      model indirect ELISA for detecting antibodies against Trypanosoma vivax in
      cattle, the author proposes the international standardisation of reagents, test
      protocol, and the expression of results of ELISA using international reference
      samples. For local standardisation, the following proposals are made: sampling of
      representative local populations. Establishment of the distribution patterns of
      infected and uninfected local populations. Selection of representative controls
      from local populations (secondary reference samples). Expression of test results
      in comparison with these controls. Establishment of internal quality control
      based on the response of controls. Determination of a positive threshold, in
      accordance with the requirements of the user. Adaptation of the positive
      threshold according to the prevalence observed in the geographical sector under
      study.

PMID- 9567308
TI  - International reference standards: antibody standards for the indirect enzyme
      linked immunosorbent assay.
AB  - Reference standards are used to calibrate similar assay systems against an
      international reference protocol and to provide a template for the preparation of
      secondary and/or working standards. Three reference standards are recommended for
      the indirect enzyme-linked immunosorbent assay: a strong positive standard, a
      weak positive standard and a negative serum standard. The negative standard
      should be derived from a single serum or from a serum pool which exhibits typical
      background activity in the reference protocol. The strong and weak positive
      standards should be derived from a single serum or from a serum pool which
      typifies the humoral response (antibody) to natural infection. Suitable
      candidates for the positive reference standards should exhibit dose/response
      curves in the mid-range of antibody activity. The strong and weak positive
      standards should each be prepared from a one-time dilution in the negative
      standard, to yield antibody activities which are defined by specific points on
      the linear portion of the dose/response curve. The strong positive standard
      should represent an antibody activity (absorbance value) midway between the upper
      and central points and the weak positive standard should represent an antibody
      activity midway between the central and lower points of the linear portion of the
      curve. Owing to inherent differences among assay systems, antibody activities
      should be expressed in relative rather than in absolute terms. It is recommended
      that the antibody activity of the strong positive standard should denote 100%
      positivity. The activities of the weak positive and negative standards should
      then be expressed as relative percentages. Every set of international reference
      standards should be accompanied by an information sheet which includes, among
      other things, a plot of the dose/response curve and an indication of the
      dilutions used to prepare the standards.

PMID- 9567309
TI  - Detection of virus infection-associated antigen and 3D antibodies in cattle
      vaccinated against foot and mouth disease.
AB  - The analysis of sera obtained from animals vaccinated or revaccinated with
      inactivated vaccines against foot and mouth disease (FMD) virus showed that these
      vaccines induced antibodies against the virus infection-associated (VIA) antigen,
      detectable by agar gel immunodiffusion (AGID). The present study evaluates the
      antibody response to protein 3D and the VIA antigen (VIAA) of FMD virus induced
      by different vaccines in a group of 51 calves. This response was detected using
      AGID and a liquid-phase blocking sandwich enzyme-linked immunosorbent assay
      (ELISA) for anti-3D antibodies (ELISA-3D). No anti-VIAA or anti-3D antibodies
      were detected after the initial vaccination. Following revaccination, animals
      giving positive results were detected by both methods. This immune response
      disappeared 60-120 days post-revaccination (dprv) according to the AGID method,
      and 90-180 dprv when ELISA-3D was used. Samples of oesophageal-pharyngeal fluid
      obtained from animals that remained positive for anti-VIAA antibodies at 90-120
      dprv gave negative results for viral isolation, indicating that the transitional
      antibody response induced by the vaccine was due to the presence of non
      structural antigens in the vaccine and not to viral infection. These results
      indicate that the ELISA-3D method could be used as a complementary method for
      sero-epidemiological studies as an indirect indicator of viral activity, as long
      as the age and vaccination status of the animals being sampled are taken into
      consideration.

PMID- 9567310
TI  - An investigation of camelpox outbreaks in two principal camel (Camelus
      dromedarius) rearing areas of Kenya.
AB  - In 1992, during an investigation into camelpox in two principal camel-rearing
      areas of Kenya, the disease was found in 1,100 camels at a prevalence of 6% in
      Turkana and 27% in Samburu. In Turkana, outbreaks were detected in two herds of
      young animals, while in Samburu, outbreaks were found in two herds of adult
      animals, as well as in two herds of young camels. In all cases, there was 100%
      morbidity in the affected herds. When young camels were involved, the main
      lesions were confined to the mouth, nose and muzzle as distinct pustular lesions.
      In adults, there was also extensive oedema of the head and neck. Direct electron
      microscopy and virus isolation on tissue culture were used to confirm the
      orthopoxvirus infection. The outbreaks appeared related to the stress of weaning
      and, in the case of the adults, to recent long-distance travel.

PMID- 9567311
TI  - Contagious agalactia of small ruminants: current knowledge concerning
      epidemiology, diagnosis and control.
AB  - Contagious agalactia of small ruminants is a syndrome which principally affects
      the mammary glands, joints and eyes. The main causal agents are Mycoplasma
      agalactiae in sheep, and M. agalactiae, M. mycoides subsp. mycoides large colony
      type and M. capricolum subsp. capricolum in goats. In addition, M. putrefaciens
      can produce a similar clinical picture, particularly in goats. Contagious
      agalactia occurs on all five continents and is often enzootic. The evolution of
      the infection tends to be chronic in affected animals and herds. Symptomless
      shedding of mycoplasmas, mainly in the milk, may persist for a long time. These
      insidious infections, associated with carriage in the ears of healthy animals,
      are difficult to diagnose and to control. The main mode of transmission between
      flocks is related to the sale of carrier animals and contact during transhumance,
      whereas transmission within a flock occurs through contact, suckling and milking.
      This review discusses the clinical features, epidemiology, treatment, prevention
      and control of the disease.

PMID- 9567312
TI  - Oral rabies vaccination of red foxes and golden jackals in Israel: preliminary
      bait evaluation.
AB  - Field trials were conducted in late April to early May of 1995 and 1996 in
      central Israel to assess the potential for controlling rabies in red foxes
      (Vulpes vulpes) and golden jackals (Canis aureus) by using vaccine-laden baits.
      Of the bait types which were field tested, polymer fish meal baits were selected
      as the most suitable for both species. Fish meal baits containing tetracycline
      hydrochloride, an oral biomarker, were distributed by four-wheel-drive vehicle at
      a density of approximately 30 baits/km2 in two test areas of 35 km2. Of the
      animals which were trapped and euthanized seven to ten days after treatment, 65%
      of foxes and 56% of jackals gave positive results when tested for the biomarker.
      These results indicate the potential effectiveness of oral rabies vaccination of
      these species in Israel and possibly elsewhere in the Middle East, where rabies
      is a problem in wild canids.

PMID- 9567313
TI  - Nocardia asteroides as a cause of pneumonia in a buffalo calf.
AB  - Pulmonary nocardiosis has been described in a four-month-old male buffalo calf
      (Bubalus bubalis) with a history of respiratory distress lasting ten days.
      Microscopic examination of tissue imprints from the infected lungs revealed
      numerous Gram-positive, acid-fast, fine, branched, filamentous organisms which
      were morphologically identical with those of Nocardia spp. Cultures of pneumonic
      lung specimens on plain Sabouraud medium yielded pure growth of Nocardia
      asteroides at 37 degrees C. Lungs from ten healthy buffalo gave negative results
      for bacteria, suggesting that N. asteroides does not occur as a commensal in the
      pulmonary tissues. Epidemiological investigation established the source of
      infection in the immediate environment of the animal. It is emphasised that N.
      asteroides may be considered to be a respiratory pathogen and should be included
      in differential diagnosis of pulmonary diseases.

PMID- 9567314
TI  - The Swiss control programme for Salmonella enteritidis in laying hens:
      experiences and problems.
AB  - The Swiss control programme for Salmonella Enteritidis began at the end of 1993.
      All efforts are focused on the elimination of infected parent and layer flocks
      and on the production of S. Enteritidis-free eggs. The new Zoonosis Order and
      more stringent import regulations help to identify S. Enteritidis-positive parent
      layer and layer flocks. Other measures, such as additional voluntary monitoring
      of parent layer flocks, hatcheries and layer flocks, increased hygiene on poultry
      farms and the use of heat-treated feed, serve to prevent the spread of S.
      Enteritidis. An important point of concern is the elimination of S. Enteritidis
      from contaminated poultry farms, particularly from free-range farms. In the last
      two years, the number of reported infections of S. Enteritidis in humans has
      almost fallen to the level of 1988 (the year before the onset of S. Enteritidis
      infection in laying hens in Switzerland).

PMID- 9567315
TI  - Decontamination of chicken carcasses artificially contaminated with Salmonella.
AB  - A study was conducted to evaluate the efficacy of three chemical disinfectants
      and of ionising radiation in reducing the level of contamination in chicken
      carcasses which had been artificially contaminated with Salmonella Virchow.
      Chicken carcasses were obtained from a local abattoir. Five carcasses and one
      control carcass were used to test each concentration of disinfectant and the
      radiation. The amount of contaminant employed was 0.5 ml of 10(4) colony-forming
      units per ml of S. Virchow spread over the thigh, breast and wing areas. All
      treatments were conducted in duplicate. The three disinfectants used were as
      follows: calcium hypochlorite, at concentrations of 20 ppm, 50 ppm, 100 ppm and
      200 ppm of available chlorine. Lactic acid at concentrations of 0.5%, 0.75% and
      1%. Hydrogen peroxide compound at concentrations of 1%, 2% and 3%. Five
      inoculated carcasses were immersed at a time in one disinfectant concentration
      for 15 min, while the control carcasses were simultaneously immersed in water
      free from disinfectants. Five carcasses, each in a plastic bag, were subjected to
      varying ascending doses (from 2 to 7 k gray [kGy]) of ionising radiation from
      radioactive isotopes of cobalt 60. A bacteriological examination of each carcass
      was conducted after the treatment to determine the presence or absence of S.
      Virchow. The number of carcasses which gave positive results showing the presence
      of Salmonella decreased after chemical treatment, but the organism was not
      completely eliminated. However, in those carcasses subjected to 7 kGy of
      radiation, Salmonella was eliminated and no changes in the appearance, colour or
      smell of the carcasses were observed.

PMID- 9567316
TI  - Recommended standards for epidemiological surveillance systems for contagious
      bovine pleuropneumonia.
AB  - The initial draft of this document was prepared in June 1993 by the Ad hoc Group
      on Contagious Bovine Pleuropneumonia Surveillance Systems of the Office
      International des Epizooties. That draft was then amended in February 1997 by the
      Group of experts convened at the request of the International Committee to
      examine issues relating to the surveillance of the disease, with particular
      reference to the effects of vaccination programmes on surveillance systems. This
      updated report includes the following: epidemiological and other factors which
      influence the choice of surveillance systems. Sampling and surveillance
      strategies. Diagnostic methods applicable to surveillance systems. The
      repercussions of vaccination on surveillance systems.

PMID- 9567317
TI  - Human immunodeficiency virus (HIV) in America, 1981 to 1997: epidemiologic and
      therapeutic considerations.
AB  - In the last 16 years, acquired immunodeficiency syndrome (AIDS) has evolved from
      a mysterious syndrome apparently afflicting only gay men, into a viral illness
      affecting every segment of society. Until the advent of combination
      antiretroviral therapy, HIV appeared to be universally fatal. New therapies and
      technologies have been developed offering normal or near-normal life spans for
      some people living with HIV. Coincident with the development of life-prolonging
      therapies has been the realization that competent HIV care requires the
      integration of medical care, social services, and psychological support services
      to promote therapeutic adherence and maximize quality of life.

PMID- 9567318
TI  - Clinical correlates of human immunodeficiency virus (HIV)-related
      immunosuppression.
AB  - Opportunistic infections and cancers, collectively referred to as opportunistic
      diseases (OD), occur with increasing frequency as HIV-related immunosuppression
      advances. Knowledge of an individual's degree of immunosuppression, as measured
      by his or her CD4 cell count, will assist a clinician in constructing a
      differential diagnosis to account for a given clinical presentation. Likewise,
      the correlation of an individual's immunosuppression with their symptoms will
      enable a radiologist to assist a clinician in determining which radiological
      studies are most likely to lead to a diagnosis.

PMID- 9567319
TI  - Diagnostic imaging of the brain in acquired immunodeficiency syndrome (AIDS).
AB  - The central nervous system is commonly involved in acquired immunodeficiency
      syndrome (AIDS), resulting in a variety of lesions and diseases. They can be
      divided into the primary effects of human immunodeficiency virus (HIV),
      opportunistic infections, tumors, and vascular disease. This article is a review
      of the major imaging findings observed in each disease, with clinical and
      pathological correlations relevant to the goal of differential diagnosis.

PMID- 9567320
TI  - The role of computed tomography in the diagnosis and management of human
      immunodeficiency virus (HIV)-related pulmonary diseases.
AB  - This review summarizes the current role of CT in the diagnosis and management of
      respiratory disease in human immunodeficiency virus (HIV)-positive patients.
      Recommendations are made concerning optimum technique for diagnostic CT as well
      as practical considerations concerning the use of CT in biopsy and thoracic
      interventional procedures in acquired immune deficiency syndrome (AIDS)-related
      thoracic disease. Clinical scenarios discussed include the use of CT when the
      chest radiograph is normal in a patient with a high clinical suspicion of
      pulmonary disease, utility of CT in the differential diagnosis of parenchymal
      abnormalities and in the assessment of patients with airways disease, hemoptysis,
      progressive lung disease, and intrathoracic complications. Finally, the use of
      thoracic CT in the staging of AIDS-related neoplastic conditions involving the
      chest is discussed.

PMID- 9567321
TI  - CT manifestations of human immunodeficiency virus (HIV)-related pulmonary
      infections.
AB  - The infectious pulmonary complications of acquired immunodeficiency syndrome
      (AIDS) are reviewed, with emphasis on the spectrum of CT imaging findings and
      diagnostic accuracy and limitations as reported in the current literature.
      Changes in epidemiologic trends for common AIDS-related infections and the
      associated ranges of CD4 lymphocyte counts, when these infections are typically
      encountered, are discussed.

PMID- 9567322
TI  - Acquired immunodeficiency syndrome (AIDS) of the abdominal organs: imaging
      features.
AB  - The liver, spleen, biliary tract, pancreas, and kidneys are commonly affected by
      opportunistic infection, malignancy, and inflammatory disorders during the course
      of human immunodeficiency virus (HIV) infection. Clinical manifestations of solid
      abdominal visceral involvement are protean and usually nonspecific, but it is
      important to establish a specific diagnosis promptly in these often critically
      ill patients. This presentation reviews the cross-sectional imaging spectrum of
      HIV-associated lesions of these organs.

PMID- 9567323
TI  - Radiologic evaluation of the acute abdomen in the patient with acquired
      immunodeficiency syndrome (AIDS): the role of CT scanning.
AB  - Abdominal complaints are common in the HIV-infected patient, and the signs and
      symptoms of disease may be masked by concurrent illness and a weak immune
      response, making accurate diagnosis difficult. Patients with acquired
      immunodeficiency syndrome (AIDS) are susceptible to diseases common to the
      general population; however, their generalized state of immunodeficiency places
      them at increased risk for many unusual disorders, predominately infectious and
      neoplastic. Radiologic evaluation, in particular, computed tomography (CT) with
      its ability to image the entire abdomen and pelvis, plays a crucial role in the
      prompt and accurate diagnosis and treatment of these patients.

PMID- 9567324
TI  - Musculoskeletal complications of the patient with acquired immunodeficiency
      syndrome (AIDS): CT evaluation.
AB  - Musculoskeletal disorders are infrequent complications of HIV infection in this
      country. However, AIDS patients are susceptible to a wide range of
      musculoskeletal complications, from the common to the otherwise uncommon. The
      following is a summary of some of the more frequently encountered musculoskeletal
      manifestations of these disorders within the HIV-positive community and their
      associated imaging characteristics.

PMID- 9567325
TI  - Bloodborne pathogens and procedure safety in interventional radiology.
AB  - Concern about possible transmission of bloodborne pathogens during medical
      procedures is growing among patients and healthcare workers alike. This fear has
      primarily been focused on nosocomial transmission of human immunodeficiency virus
      (HIV), but other bloodborne infectious agents may also be transmitted during
      procedures. Chief among these are the hepatitis viruses, particularly hepatitis B
      virus (HBV) and hepatitis C virus (HCV), both of which are significantly more
      widespread than HIV. Although radiology is not traditionally thought of as a
      field with significant risk for exposure to or transmission of pathogens, the
      expanding role of interventional procedures in recent years belies that
      perception. The potential for exposure to blood or other possibly infectious
      material exists in virtually any invasive radiological procedure, from
      arteriography to image-guided biopsy. Fortunately, the risk of such exposure is
      low, and the risk of actual transmission of a bloodborne pathogen, whether from
      patient to healthcare worker or vice versa, is even lower. Nevertheless, it is
      important for all radiologists who perform invasive procedures to be aware of
      these risks and to observe pertinent safety and infection control
      recommendations. This article will review these topics.

PMID- 9567326
TI  - Bioactive furonaphtoquinones from Tabebuia barbata (Bignoniaceae).
AB  - Tabebuia barbata (E. Mey) Sandw. (Bignoniaceae), locally known as "palo de arco",
      is indigenous to the upper Orinoco and Amazonas rivers. Brine shrimp lethality
      directed fractionation and extensive column chromatography, normal-phase
      preparative TLC and normal-phase HPLC separation of the ethanol extract of the
      bark of this previously uninvestigated species has led to the isolation of five
      active compounds 1-5. The combined spectral evidence (UV, IR, 1H and 13C NMR and
      mass) identified these compounds as naphthoquinones. These compounds,
      characterized as lapachol (1), 2-acetylnaphtho-[2,3-b]-furan-4,9-dione (2), 2
      acetyl-5-hydroxy-naphtho-[2,3-b]-furan-4,9-dione (3), 2-acetyl-8-hydroxy-naphtho
      [2,3-b]-furan-4,9-dione (4), and (+)-8-hydroxy-2(1-hydroxy-ethyl) naphtho-[2,3-b]
      furan-4,9-dione (5), were reported previously from other species of the genus
      Tabebuia but not from T. barbata. Compounds 2-5, reference adriamycin, were
      significantly cytotoxic against A-549 human lung adeno-carcinoma, MCF-7 human
      breast carcinoma, and HT-29 human colon carcinoma cells. The compounds isolated
      (1-5) were also shown to be inhibitors of electron transport in rat liver
      mitochondria, reference to rotenone, with IC50 values in the range of 15 microM
      to 82.5 microM. In addition, this study demonstrated that screening and activity
      directed fractionation, using brine shrimp lethality as a simple and inexpensive
      bioassay, can effectively lead to potential antitumor compounds.

PMID- 9567329
TI  - [Systemic arterial hypertension. A disease programmed in the uterus?].

PMID- 9567328
TI  - [Antibiotic prophylaxis of infectious endocarditis. The need for longer
      observation?].

PMID- 9567327
TI  - [Molecular modeling of N-isopropyl lisergamides analogous to LSD using molecular
      mechanics and quantum mechanical calculations].
AB  - Molecular mechanics and quantum mechanics were used to study the preferred
      conformations, electron densities and frontier orbitals of d-LSD and their
      analogs with the isopropyl amide group, compounds with reported activity over the
      serotonin receptor. Electron densities and frontier orbitals for isopropyl
      analogs were similar to d-LSD, so these properties can not be related with the
      changes in biological activity previously reported. It was found that isopropyl
      analogs have preferred conformations similar to d-LSD with small variation in the
      alkylamide group. The variation in the alkylamide group causes small variations
      in the orientation of the carbonyl amide group, our study suggests that this
      variation could affect the binding with the hydrophobic region of the receptor.

PMID- 9567330
TI  - [Cardiac amyloidosis. A disease with many faces and different prognosis].
AB  - PURPOSE: To identify the principal forms of cardiac amiloydosis presentation in a
      terciary hospital. METHODS: Eight cases with cardiac amyloidosis were identified.
      Five were women, their ages ranged from 23 to 83 years (mean 62). After a medical
      history and clinical examination the patients were submitted to complementary
      tests: electrocardiogram (EKG), echocardiogram (ECHO), scintigraphy with
      technecium pirophosphate and cardiac biopsy these results allowed the
      identification of their clinical situation. RESULTS: Seven patients referred
      dyspnea, 6 were in heart failure, 1 patient had syncope. The EKG identified
      complete atrioventricular (AV) block in 4 patients, and antero septal inactive
      area in the other 4. The ECHO showed normal cardiac diameter in all (mean left
      ventricular diastolic diameter of 46.8) and slight reduction of left ventricular
      ejection fraction; hypertrophy of the left ventricular septal and posterior walls
      in all cases, in 7 cases there was a hyper refractile granular sparkling ECHO.
      Two different groups were identified: one with complete AV block and the second
      with restrictive cardiomyopathy. The prognosis was different in these two groups.
      Those with complete AV block evolved better after pacemaker implantation and
      those with restrictive cardiomyopathy had refractory heart failure and 3 of them
      died. CONCLUSION: The increased free wall and septal thickness, the slight
      systolic dysfunction and the infiltration aspect at ECHO allow us to identify the
      great majority of the cases. Those patients with restrictive cardiomyopathy
      evolve with refractory heart failure and most of them die in a few months.

PMID- 9567331
TI  - [Prognostic value of stress echocardiography by dobutamine combined with
      atropine].
AB  - PURPOSE: To determine the prognostic value of dobutamine-atropine stress
      echocardiography (DASE). METHODS: We studied 452 consecutive patients at high
      risk for coronary artery disease, using DASE. They were followed during a mean
      period of 23 months. RESULTS: There were 9 cardiac deaths and 2 acute myocardial
      infarctions in the group of patients with positive tests, and there were 2
      myocardial infarctions and 1 cardiac death in patients with negative DASE.
      CONCLUSION: We conclude that DASE reliably identifies patients at high risk for
      hard cardiac events.

PMID- 9567332
TI  - [Activation of the cardiac angiotensin-converting enzyme after myocardial
      infarction and its role in ventricular remodeling].
AB  - PURPOSE: To determine angiotensin converting enzyme (ACE) activity in the heart
      of infarcted rats and to investigate the effects of captopril and losartan on the
      post-infarction remodeling process. METHODS: Myocardial infarction (MI) was
      produced in Wistar rats by ligature of the left coronary artery. Control rats
      (Con) underwent a sham surgery. MI and Con rats remained untreated or were
      treated with captopril (30 mg/kg/day) or losartan (15 mg/kg/day) for 30 days. ACE
      activity was determined in right (RV) and left ventricular (LV) muscles and in
      the scar tissue. The effects of captopril therapy was also investigated in the
      hydroxiproline (OH-Pro) and protein in RV and LV. RESULTS: ACE activity increased
      25% in the RV and 70% in the remaining LV muscle. The highest ACE activity was
      found in the scar tissue, where it was 4.5 times the value of the LV muscle (420
      +/- 68 vs 94 +/- 8 nmoles/g/min; P < 0.01). An increase of the end-diastolic
      pressure and of the muscle mass was found in the RV and LV of MI rats. Captopril
      and losartan treatments were equally efficient to attenuate these parameters in
      both ventricles. Captopril also reduced the total OH-Pro content in the RV and LV
      muscles. The Prot concentration was significantly reduced in the myocardium of MI
      rats, an effect enhanced by captopril therapy. CONCLUSION: The AII concentration
      in the blood draining from the scar to the surrounding muscle is probably high.
      It is likely that this elevated local generation of AII contributes to
      hypertrophy and to collagen deposition. The effects of ACE inhibitors on
      remodeling are likely to depend on the reduction of the locally generated AII.

PMID- 9567333
TI  - [Late evaluation with spiral computed tomography of smooth bovine pericardium
      grafts].
AB  - PURPOSE: To evaluate morphologically by spiral computed tomography (SCT) bovine
      pericardial grafts as aortic substitutes. METHODS: Ten patients were submitted to
      aortic graft evaluation with SCT. There were 8 ascending and 2 descending grafts.
      Examination was done after 2 to 7 years post operative. Ages ranged from 49 to 67
      years, with 6 male and 4 female patients. All had implanted smooth surface naked
      pericardial grafts. RESULTS: Surgical result was good in all. Distal dissection
      persisted in some cases. One had a peri-graft hematoma, 5 had no structural
      changes and 4 presented mild graft dilatation. There were no graft calcification
      or pseudoaneurysm. CONCLUSION: Glutaraldehyde preserved naked smooth surface
      bovine pericardial aortic grafts present satisfactory structural aspect, as seen
      by SCT, at medium term follow-up. Mild dilatation may be seen in some cases.

PMID- 9567334
TI  - [Is the apical hypertrophic cardiomyopathy seen in one population in Rio de
      Janeiro city similar to that found in the East?].
AB  - PURPOSE: To investigate the differences between clinical aspects and evolution of
      apical hypertrophic cardiomyopathy (AHCM) seen in Rio de Janeiro and the Oriental
      form, which was the first described. METHODS: In 156 patients with AHCM diagnosed
      in our institution, there were 13 (8.34%) with the apical form of the disease,
      whose clinical settings, diagnostic procedures and evolution were studied.
      RESULTS: There were 8 males and 5 females, between 19 and 75 years old, all
      white. Electrocardiogram (EKG) showed giant T waves in precordial leads in 10
      (76.92%), echocardiogram (ECHO) demonstrated apical hypertrophy in all, 10
      (76.92%) had only in the left ventricle, 2 in right ventricle and one involving
      both. Cineangiography corroborated ECHO findings. Follow-up ranged from 6 to 294
      months (x = 95.4). Two deaths occurred in patients with RV involvement, due to
      large atria, atrial fibrillation, tricuspid or mitral insufficiency and
      thromboembolism. Among the survivors, the patient with RV disease has diastolic
      restriction and the ones with LV involvement, 9 are asymptomatic using either
      propranolol (8) or amiodarone (1), and one uses no medication. CONCLUSION: A HCM
      seen in Rio de Janeiro is similar to that found in the Orient (Japan) regarding
      presentation, diagnosis and evolution; but in 3 patients we have found RV
      disease, not described in Japan, characterizing a distinct group with a worse
      evolution.

PMID- 9567335
TI  - [Retroesophageal hematoma with severe dysfagia after streptokinase for the
      treatment of the axillosubclavian vein thrombosis].
AB  - We report the case of a 72 year-old man with advanced, stage IV, prostate cancer
      who underwent osteosynthesis of the cervical spine for nerve root decompression
      due to metastasis which was causing severe pain in his right upper limb. After
      three months in the hospital, he developed occlusive thrombosis of the right
      axillosubclavian vein as a complication of prolonged catheterization of the right
      subclavian vein for treatment of septicemia secondary to a hospital acquired
      pneumonia. The patient received thrombolytic therapy with IV streptokinase in the
      contralateral arm in the following dosage: 250,000 units in 15 minutes followed
      by 100,000 units per hour during five days. This led to total recanalization of
      the thrombus, with significant reduction of the arm edema. Twenty-four hours
      after the end of the thrombolytic therapy, the patient started to complain of
      dysfagia to solids and liquids and a contrasted esophagogram revealed extensive
      extrinsic compression of the esophagus due to a probable retroesophageal
      hematoma. The patient required enteral nutrition via nasoenteral tube during
      three months after which swallowing returned to normal and a repeat upper GI
      series confirmed that the hematoma had been reabsorbed, with normal passage of
      contrast through the esophagus. On late follow-up, the patient did not show
      evidence of any sequelae of deep venous thrombosis nor any residual dysfagia and
      is currently in use of elastic stockings and low molecular weight heparin.

PMID- 9567336
TI  - [Unstable angina due to communication between the coronary artery and the right
      pulmonary artery in patient with Takayasu's arteritis].
AB  - A sixty three year old woman suffering from Takayasu's arteritis with involvement
      of the aortic arch, subclavia arteries and occlusion of the right pulmonary
      artery, developed progressive precordial pain. Exercise electrocardiogram
      disclosed ST segment depression. Coronary arteriograms demonstrated no coronary
      stenosis, but collateral circulation arising from circumflex coronary artery to
      right pulmonary artery. The collateral blood flow was considered to be of great
      importance, and causing the coronary steal syndrome, leading to angina pectoris.

PMID- 9567337
TI  - [Partial ventriculectomy in a child--the Batista technique].
AB  - We present the case of a two and a half year old child with idiopatic dilated
      cardiomyopathy and end-stage congestive heart failure (NYHA III-IV) who underwent
      "partial ventriculectomy". The operation was performed under normothermic
      cardiopulmorary bypass and normothermic oxygenated blood cardioplegia and
      consisted of removal of a large wedge of muscle from the lateral wall of the left
      ventricle beginning at the apex and extending between the papillary muscles,
      ending proximal to the mitral annulus. Pre-operative the left ventricular
      ejection fraction (EF) was 13% by echocardiography and 20% by radionuclide
      ventriculography. Postoperative avaliation showed improvement of EF to 50% and
      30%, respectively. The child was in functional class I (NYHA) on discharge from
      hospital (16th postoperative day).

PMID- 9567338
TI  - [Anatomopathological correlation. (Case 5/97--Instituto do Coracao do Hospital
      das Clinicas-FMUSP)].

PMID- 9567339
TI  - [Postangioplasty restenosis. Physiopathogeny].

PMID- 9567340
TI  - [Retrovirus and cancer revisited].
AB  - The discovery of RNA oncoviruses dates back to 1911 when Rous isolated the avian
      virus which is the cause of the sarcoma which bears his name and to 1936 when
      Bittner related the "milk factor" to the development of murine mammary cancer.
      During the 50s, the successive descriptions of virus-induced sarcoma-leukemias in
      mice led to the oncogene theory and gradually to the postulation of a viral
      origin of cancer. The discovery of the reverse transcriptase in 1970 led to the
      establishment of the Retroviridae family including both onco and lentiviruses.
      The decade of the 80s was marked by three fundamental discoveries which altered
      the concept of oncovirus: 1) oncogenes became established as part of the cellular
      genome converting retroviruses into occasional vectors of the oncogene; 2) as the
      T cell growth factor, interleukin-2, became available, the first human oncovirus,
      HTLV-I, was isolated and proved to be the cause of adult T cell leukemia; 3) HIV
      was isolated and classified as a lentivirus and as the cause of AIDS. A few years
      later the antioncogenes were discovered. Both oncogenes and anti-oncogenes were
      found to collaborate in the cell cycle, maintaining an equilibrium between
      proliferation and apoptosis. Today the viral theory has been replaced by the gene
      theory of cancer which postulates that neoplastic transformation is the result of
      a cascade of events which include uncorrected DNA errors, blocking of apoptosis,
      activation of oncogenes and deletion of antioncogenes. At the present time, the
      intriguing question for retrovirologists is the role played by endogenous
      retroviruses which in man occupy up to 0.1% of the cellular genome.

PMID- 9567341
TI  - [Superantigens and murine mammary tumor retrovirus].
AB  - Hosts and their pathogens have co-evolved for millions of years, developing
      multiple and intimate interactions. Vertebrates have evolved a very complex
      immune system which pathogens have often been able to circumvent, in some cases
      even managing to appropriate some of its components for their own purpose. Among
      the pathogens which do use components of the immune system to survive and
      propagate, those coding for the expression of superantigens (SAgs) are now under
      intense scrutiny. Investigations concerning one of these pathogens, the mouse
      mammary tumor virus (MMTV), led to the understanding of how the expression of
      such components is a critical step in their life cycle. A number of milk-borne
      exogenous MMTV infect mice shortly after birth and, when expressed, produce
      superantigens. Herein, we describe the biological effects of new variants of
      MMTV. Two of these, BALB14 and BALB2 encoding SAgs with V beta 14+ and V beta 2+
      specificities, respectively, were present in BALB/c mice of our colony (BALB/cT);
      a third variant, termed MMTV LA, originated in (BALB/cTxAKR)F1 mice from
      recombination between BALB 14 and Mtv-7 endogenous provirus. The recombinant LA
      virus induces the deletion of V beta 6+ and V beta 8.1+ T cells as a consequence
      of the acquisition of SAg hypervariable coding region of Mtv-7. The SAg encoded
      by MMTV LA strongly stimulates cognate T cells in vivo leading to a very
      effective amplification of lymphoid cells in BALB/c mice, correlating with a high
      incidence of mammary tumors. These results suggest that the presence of non
      productive endogenous proviruses--generally considered to confer a selective
      advantage to the host by protecting it from infection with exogenous MMTVs
      encoding cross-reactive SAgs--could also be advantageous for the pathogen by
      increasing its variability, thus broadening the host range and allowing the
      expansion of highly tumorigenic variants.

PMID- 9567343
TI  - Retrovirus-host interactions. The mouse mammary tumor virus model.
AB  - Mouse mammary tumor virus (MMTV) is a retrovirus which can induce mammary
      carcinomas in mice late in life by activation of proto-oncogenes after
      integration in their vicinity. Surprisingly, it requires a functional immune
      system to achieve efficient infection of the mammary gland. This requirement
      became clear when it was discovered that it has developed strategies to exploit
      the immune response. Instead of escaping immune detection, it induces a vigorous
      polyclonal T-B interaction which is required to induce a chronic infection. This
      is achieved by activating and then infecting antigen presenting cells (B cells),
      expressing a superantigen on their cell surface and triggering unlimited help by
      the large number of superantigen-specific T cells. The end result of this strong
      T-B interaction is the proliferation and differentiation of the infected B cells
      leading to their long term survival.

PMID- 9567342
TI  - Mouse mammary tumor virus (MMTV), a retrovirus that exploits the immune system.
      Genetics of susceptibility to MMTV infection.
AB  - All animals, including humans, show differential susceptibility to infection with
      viruses. Study of the genetics of susceptibility or resistance to specific
      pathogens is most easily studied in inbred mice. We have been using mouse mammary
      tumor virus (MMTV), a retrovirus that causes mammary tumors in mice, to study
      virus/host interactions. These studies have focused on understanding the
      mechanisms that determine genetic susceptibility to MMTV-induced mammary tumors,
      the regulation of virus gene expression in vivo and how the virus is transmitted
      between different cell types. We have found that some endogenous MMTVs are only
      expressed in lymphoid tissue and that a single base pair change in the long
      terminal repeat of MMTV determines whether the virus is expressed in mammary
      gland. This expression in lymphoid cells is necessary for the infectious cycle of
      MMTV, and both T and B cells express and shed MMTV. Infected lymphocytes are
      required not only for the initial introduction of MMTV to the mammary gland, but
      also for virus spread at later times. Without this virus spread, mammary
      tumorigenesis is dramatically reduced. Mammary tumor incidence is also affected
      by the genetic background of the mouse and at least one gene that affects
      infection of both lymphocytes and mammary cells has not yet been identified. The
      results obtained from these studies will greatly increase our understanding of
      the genetic mechanisms that viruses use to infect their hosts and how genetic
      resistance to such viruses in the hosts occurs.

PMID- 9567344
TI  - [Progestin-induced mammary adenocarcinomas in BALB/c mice. Progression from
      hormone-dependent to autonomous tumors].
AB  - We have developed an experimental model in which the administration of progestins
      induces mammary tumors in female virgin BALB/c mice. In this paper we review the
      morphological and biological features of progestin-induced tumors, such as
      estrogen receptor (ER) and progesterone receptor (PR) patterns of expression,
      hormone dependence and epidermal growth factor receptors (EGF-R) we also examine
      our data concerning the systemic effects of medroxyprogesterone acetate (MPA) as
      regards its stimulating EGF synthesis in salivary glands and its subsequent
      increase in serum. This growth factor seems to play an important role in the
      induction of mammary tumors. Direct MPA proliferative effects mediated by PR were
      demonstrated using primary cultures of progestin-dependent (PD) mammary tumors.
      Antiprogestins inhibited cell growth beyond control values, suggesting that PR
      are involved in cell proliferation even in the absence of the ligand.
      Progesterone-independent (PI) tumors expressing high levels of PR and ER are also
      inhibited by estrogen or antiprogestin treatment, suggesting that PR are involved
      in the control of autonomous tumor growth. Estrogen-resistant variants may be
      selected which may revert to an estrogen-sensitive phenotype after several
      transplants in untreated mice. The similarities between the tumors obtained with
      this model and human breast cancer as regards morphological features, evolution
      and the regulation of growth control converts this model into a useful tool to
      explore the mechanisms related with acquisition of hormone independence and
      autonomous tumor growth.

PMID- 9567345
TI  - [Searching for retroviral sequences related to human breast cancer].
AB  - The participation of viruses in mammary carcinogenesis has been largely studied
      in animals. A model similar to the mouse mammary tumor virus (MMTV) was
      previously proposed. Several lines of research supported the participation of
      MMTV in human breast cancer, but these evidences were contradicted when further
      research was performed. One major issue was the presence of human endogenous
      retroviral sequences that confounded results reporting MMTV-like sequences in
      human breast cancer. To overcome this problem we selected a 660 bp sequence of
      the MMTV env gene with low homology to endogenous sequences and search for a
      sequence to it using the polymerase chain reaction (PCR). The sequence was found
      in 38% of the human breast cancers and in 2% of the normal breasts studied. The
      sequence was not present in tumors from other organs. It was 90-98% homologous to
      MMTV and only 18% to human endogenous retrovirus (HERV) K-10. It was also
      detected in some of the positive tumors by Southern blot hybridization using one
      of the cloned 660 bp as a probe. Using reverse transcriptase PCR, it was possible
      to demonstrate that the 660 bp sequence is expressed in the majority of the
      tumors. Also, preliminary experiments revealed that sequences related to the LTR
      and gag genes of MMTV were present in the DNA of breast tumors. The origin of the
      MMTV-like sequences in tumor DNA could be the result of integrated MMTV-like
      sequences derived from a human mammary virus or may represent unknown endogenous
      sequences that can only be detected in breast tumors.

PMID- 9567346
TI  - Differentiation and breast cancer.
AB  - The mammary gland is an organ whose size, shape and function undergo fundamental
      changes during the various phases of a woman's growth. Although the development
      of the mammary gland begins during infancy, the most dramatic changes occur with
      the initiation of puberty. Pregnancy and lactation complete the functional
      development of the organ, which regresses during menopause. Epidemiological and
      experimental studies have demonstrated that certain hormonal influences,
      especially those related to reproduction, modify the risk of developing breast
      cancer. Thus, a full term pregnancy completed before the age of 24 years
      significantly reduces the lifetime incidence of breast cancer. Although the
      mechanism through which pregnancy protects the breast from breast cancer has not
      been clearly established, experimental models of mammary carcinogenesis have
      allowed researchers to determine that pregnancy inhibits the initiation of the
      neoplastic process through the induction of a complete differentiation of the
      mammary gland. This process activates specific genes, which in turn modify the
      response of the organ to ulterior hormonal changes. It is postulated that the
      same mechanism might be responsible for the protective effect of a woman's early
      first full term pregnancy. The greater incidence of breast cancer observed in
      nulliparous women correlates well with the greater susceptibility of the virgin
      rat to develop mammary carcinomas when exposed to chemical carcinogens. The
      successful induction of malignant transformation in the virgin animal mammary
      epithelium is due to the presence of undifferentiated structures with a high rate
      of cell proliferation. These structures are eliminated by pregnancy. The breast
      of nulliparous women retains those undifferentiated structures, which increase
      the predisposition of the organ to undergo malignant transformation, which will
      manifest itself clinically several years after its initiation. The correlation of
      human epidemiological, clinical and experimental data with those data obtained in
      rodent experimental models lends support to this hypothesis.

PMID- 9567348
TI  - A lifetime of bisphosphonate.

PMID- 9567347
TI  - [The bisphosphonate project: 25 years of evolution].

PMID- 9567349
TI  - [Morphological studies of hydroxyapatite crystals exposed to disodium
      pamidronate].
AB  - "In vitro" effects of disodium pamidronate on hydroxyapatite crystals morphology,
      and some "in vivo" data from bone powder of tibia and vertebrae from treated
      young and mature rabbits are here reported. Hydroxyapatite, synthesized following
      Rigoli et al method, and bone powder from rabbits were studied with X-ray,
      infrared and raman emission techniques for crystallographic analysis. Adsorption
      studies were also performed with a balanced solution of hydroxyapatite exposed to
      different times, 48, 120 and 168 hours and concentrations 1 x 10(-5) M, 3 x 10(
      5) M, 8 x 10(-5) M y 1 x 10(-4) M of pamidronate. Infrared and raman spectrometry
      were not conclusive due to technical bias, but X-ray difractograms showed pure
      hydroxyapatite crystals in an hexagonal system. At constant time, pamidronate
      concentrations were varied, showing after 48 hours of exposition, a slight growth
      in the 002 plane, an aleatoric behavior in 213 and a marked increase in 004.
      After 120 hours, 002 plane is steady with a net growth in 004 and 213. After 168
      hours, the 3 mentioned planes grow in proportion to pamidronate concentrations,
      tending to enlarge the crystal shape. Plane 13 markedly grow with pamidronate 8 x
      10(-5) M a 1 x 10(-4) M, which are biologically high concentrations.
      Potentiometric assessments, in the 1 x 10(-5) to 1 x 10(-4) M range of
      concentrations show that bisphosphonate was completely adsorbed to the crystals.
      Additional "in vivo" observations showed changes in bone powder crystals isolated
      from pamidronate treated young animals, involving a growing of planes 002 and
      211, in samples from both epiphysis and diaphysis, regarding untreated samples.
      Changes were more evident at epiphysis. In mature rabbits, it was shown a
      decrease in basal plane 002 and growing at 210, 211 and 310 with a trend to
      enlarge the crystal shape in diaphysis and to shorten it in vertebrate spongiosa.
      The "in vivo" doses are equivalent to those used by Ferretti et al. in intact
      rats with pamidronate low dose groups, showing an improvement of bone material
      properties and stiffness. Thus, it may rather be lower than the "in vitro" used
      concentrations. In concordance with above experimental conditions it can be
      concluded that bisphosphonates exert morphological changes in hydroxyapatite
      crystals, in a dose dependent manner, at least when high concentrations are used.
      In addition, it is postulated that changes observed on "in vivo" samples may be
      the result with other adaptative factors as for example the local mechanical
      usage. The latter data were limited, and should be studied with more details if
      an extrapolation to the bisphosphonate treated osteoporotic women is intended.
      Finally, it is suggested that any agent that changes BMU activity (all known anti
      osteoporotic drugs) may potentially modify the quality of hydroxyapatite
      crystals, affecting in turn the bone resistance to fracture, independently from
      the quantity of bone mass gained. Thus, to help predicting the consequences on
      skeletal fragility, there is a need to know the direct or indirect effect of
      drugs on bone crystals.

PMID- 9567350
TI  - [Experimental effects of olpadronate and pamidronate on bone mass].
AB  - Ovariectomy and immobilization in rats have demonstrated to be useful models for
      osteopenia and they are considered to mimic some aspects of human osteoporosis
      associated with a deficit of ovarian hormones and the absence of mechanical
      function (disuse of the bone). Pamidronate (APD) and Olpadronate (OLPA), a new
      dimethylated aminobisphosphonate, on a continuous oral scheme (APD: 8 and OLPA:
      0.8 mg/kg/day) or on an intermittent parenteral scheme (APD: 1.25 and OLPA: 0.075
      mg/kg every 15 days) did effectively prevent the trabecular bone loss caused by
      immobilization (unilateral sciaticectomy), by lack of ovarian stimuli (bilateral
      ovariectomy) or by both approaches. There were no signs of deterioration in the
      cortical bone mass. In a model of preestablished osteopenia, caused by estrogen
      deprivation, OLPA stopped the progression of the bone mass loss (0.5 mg/kg/i.v.
      every 15 days) and restored (0.30-0.60 mg/kg/i.v. every 15 days) the bone mineral
      density which had been affected (trabecular and cortical). The different activity
      of OLPA and APD on trabecular and cortical regions of long bones seems to
      accompany their different responses because of negative stimulus: better
      responses were more evident in the trabecular bone which proved to be more
      labile. In these "in vivo" models of OLPA's efficacy was similar to APD's but it
      was roughly 5-10 times more potent. OLPA has a high safety margin. Therefore, it
      could advantageously be used in those bone diseases which benefit with the use of
      bisphosphonates.

PMID- 9567351
TI  - [Treatment of Paget's disease with olpadronate. Its efficacy in partial
      responders to oral pamidronate].
AB  - Bisphosphonates are the treatment of choice in patients with Paget's disease.
      However in patients with an extensive disease it has been difficult to achieve
      complete biochemical remission. We studied the efficacy of the new
      bisphosphonate: olpadronate (dimethyl APD) in 37 patients (21 men and 16 women)
      with Paget's disease of (mean +/- 1SD) 68 +/- 8 years of age: Group I: 12
      patients without previous specific treatment. Group II: 25 patients who had been
      treated before (time free of treatment before olpadronate: 11 +/- 8 months).
      (Table 1). Olpadronate was given orally in doses of 100 to 200 mg/day. Initial
      dose and/or increment of the dose during treatment were decided accordingly to
      the biochemical response. The length of therapy was (mean +/- 1SD) 3.5 +/- 2.4
      months (range 0.5-13 months) and was adjusted to the changes produced upon the
      biochemical indexes of bone turnover. Olpadronate was well tolerated by all the
      patients except for one who discontinued the treatment due to gastrointestinal
      symptoms. Mean alkaline phosphatase (APh) decreased in both groups of patients as
      follows: Group I: basal: 36 +/- 20 KAU, final: 12 +/- 3 KAU (normal range: 5 to
      15 KA units) and group II: basal 45 +/- 30 KAU final 14 +/- 10 KAU. (Table 2).
      Normalization of APh was observed in all patients of group I and in 21/25
      patients of group II. Three patients of group II had partial responses (60% of
      diminution of APh without reaching normal values) and treatment was not effective
      in 1 patient. The length of remission was 8.7 +/- 5.7 months in group I and 10.4
      +/- 8.1 months in group II. There was a significant inverse correlation between
      duration of remission and APh level post treatment. Fourteen patients of group II
      (7 women and 7 men) had previously received oral pamidronate (APD) in different
      cycles during a period of 6.6 +/- 4.2 years. After the first APD cycle, only 2
      out of 14 achieved normal APh values and none of the 14 achieved complete
      biochemical remission after the last APD cycle. Olpadronate caused a significant
      decrease of serum APh and THP compared to the lowest values observed during APD
      treatment. Normalization of APh was observed in 12/14 of these partial responders
      to APD. (Table 3 and Figure 1). In conclusion, oral Olpadronate in a dose of 100
      to 200 mg was well tolerated and effective in the treatment of Paget's disease
      even in those previous partial responders to APD.

PMID- 9567352
TI  - [New spine and non-spine fractures in 871 women/year treated with oral
      pamidronate plus calcium and vitamin D supplements].
AB  - A sample of 871.3 patients/year was conformed by 205 postmenopausal women, aged
      64.8 +/- 18.2 years (mean +/- SD), followed up during 51 +/- 12 months. All have
      osteoporosis, diagnosis assessed through radiological findings of at least one
      atraumatic fracture or vertebral crush ("severe osteoporosis" according to the
      new WHO classification). Each woman received 100 mg/day oral pamidronate (enteric
      coated soft gelatin capsules), half an hour before breakfast. Additional calcium
      and vitamin D were supplemented as follows: Total daily calcium = 1 g provided by
      diet and/or calcium carbonate. Vitamin D equivalent to 400-1200 IU/day. All
      patients were recommended to improve their physical activity, at least by walking
      exercise. Clinical examination radiological, bone mineral density (BMD) and
      biochemical studies were periodically performed. But, fracture indicence was the
      end-point of the study. Same was related to the 1,673 fall episodes recorded in
      the sample. In addition, height loss, lumbar BMD, proximal femur BMD, are also
      reported. Data has been cross-sectional collected in March 1995. All patients
      improved the symptomatology, specifically pain. This, and the good tolerability
      of the treatments proved to be considerably favorable for their compliance.
      Within the observation period, only 12 patients decreased their height (5.85%;
      mean = 0.85 cm; range = 0.5-2.0 cm). Lumbar spine BMD increased in 90% of 48
      women. Mean gain after 2 years was 5.3 +/- 1.0% (p < 0.001). Proximal femur
      increased in 78% of other 32 women. Mean gain 6.3 +/- 0.7% (p < 0.001) after 2
      years. A total of 78 new fractures were recorded, 47 vertebral crush, 29 forearm
      fractures and 2 hip fractures. Its incidence related to the fall episodes was of
      2.8; 1.7 and 0.12% respectively. When compared with a historical estimated data,
      from an untreated population (Cummings SR et al, 1994), both, the total number of
      new fractures and the new hip fractures were significantly lower (p < 0.01) in
      our treated population than the reference data. Pamidronate, in oral doses of 100
      mg/day, adequately supplemented with calcium and vitamin D, proved to be
      effective and a well tolerated therapy. The low rate of height's loss, BMD
      significant increases in subgroups of patients and the low rate of new fractures,
      strongly support the use of the compound to treat severe osteoporotic women. To
      our knowledge, this is the first time, that the new fracture incidence is related
      to the fall frequency reported in a bisphosphonate treated sample.

PMID- 9567353
TI  - [Extended use, up to 6 years, of an oral amino-bisphosphonate in patients with
      established osteoporosis].
AB  - In osteoporotic women (n:163), 63.8 (+/- 8.1) years old and 15.2 (+/- 8.3) years
      since menopause, oral (200 mg/day) pamidronate was administered during protracted
      periods, up to 6 years. During the first 4 years of therapy significant increases
      from basal in both, lumbar spine and femoral neck were reported (p < 0.01).
      Patients who underwent to 5-6 years of treatment also showed positive results in
      both skeletal sites. Whole body mineral content estimated a 23.8 g/year mean gain
      during a 4-year period. Biochemical bone markers of resorption and formation
      reflected a variable degree of bone turnover decrease. Such changes were more
      pronounced at the beginning, and remained steady after the first year of
      continuous therapy. Calcemia remained between normal range without any
      hypocalcemic episode being reported. Phosphatemia, within normal range, showed a
      smooth trend to increase. PTH remained within normal range and vitamin D tended
      to slightly increase. The total number of new bone fractures and total number of
      patients with new fractures were less frequent during the pamidronate treatment
      period than before (p < 0.01). Indeed, the relative risk (RR) of fracture was
      estimated comparing the treatment lapse, 495 patient/year, vs a pretreatment
      period of 1,814 patient/year. Overall RR resulted less than 1 (RR = 0.83; CI 95%
      = 0.53-1.26). In total, hip, forearm and "other" fractures, RR was also less than
      1 and remained over 1 in vertebral fractures. The latter can be explained because
      our sample started its treatment probably in a period of increased spine
      crushing. Overall fracture results, in a sample of patients as own controls and
      in spite of differences in ages, suggested that during treatment, patients
      improved their skeletal biomechanical competence, mainly in sites where cortical
      bone plays a meaningful role, as in femoral neck. It is concluded that
      pamidronate is an effective tool to ameliorate the skeletal conditions of
      postmenopausal osteoporotic women.

PMID- 9567354
TI  - [Role of bones in the physiopathology of idiopathic hypercalciuria: effect of
      amino-bisphosphonate alendronate].
AB  - Previous studies from our laboratory demonstrated that bone mineral content is
      affected in patients with idiopathic hypercalciuria and that there is a
      correlation between bone mineral loss and in-vitro cytokine production. At the
      same time we found that short term treatment with alendronate decreased urinary
      calcium in these subjects. In the present study we have examined the long-term
      effects of alendronate treatment (10 mg/day for one year) on urinary calcium,
      urinary hydroxyproline and bone mineral content in 18 idiopathic hypercalciuric
      and 8 normocalciuric stone formers. Clinical characteristics, as well as gender
      and age distribution were similar in both groups. Urinary calcium and
      hydroxyproline, were measured monthly. Calcium excretion decreased significantly
      at the end of the first month, and remained lower thereafter (277 +/- 28, before
      vs. 202 +/- 26 mg/g creatinine, after 12 months on alendronate, p < 0.01).
      Urinary hydroxyproline decreased significantly during the study (125.5 +/- 32.1
      vs. 39.66 +/- 17.5 mg/g creatinine, p < 0.05). Serum calcium, glomerular
      filtration rate, and urinary sodium, did not change during the study. Lumbar
      spine bone density (trabecular bone) obtained with X ray absorptiometry revealed
      a significant increase from 1.162 +/- 0.231 to 1.197 +/- 0.248 g/cm2 (p < 0.01).
      These changes were associated with a significant decrease in IL-1 alpha mRNA
      transcription by unstimulated and lipopolysaccharide stimulated blood mononuclear
      cells, as tested by the reverse transcriptase polymerase chain reaction. No
      changes were observed in bone cortical sites (femoral neck). Normocalciuric
      subjects showed no significant changes in urinary calcium. In summary, the
      changes observed in urinary calcium excretion and different bone metabolic
      parameters, suggest a role of bone in the pathophysiology of idiopathic
      hypercalciuria.

PMID- 9567355
TI  - [Effects on bone mass of oral alendronate, hormone replacement therapy and
      combined regimes in post-menopausal women: preliminary report on a comparative
      study].
AB  - The results of a prospective study that compared the short term effects on
      skeletal bone of oral alendronate, transdermal hormone replacement therapy (HRT)
      and two combined regimens with both medications are reported. Ninety six
      posmenopausal women with osteopenia (WHO classification) in lumbar spine or
      femoral neck measured by DEXA (table 1) were included in 4 therapeutic groups:
      Group I (n:19): 17 beta-Estradiol 50 micrograms daily
      transdermally/medroxiprogesterone 2.5 mg orally per day; Group II (n:42):
      alendronate 10 mg/day orally; Group III (n:15): HRT + alendronate 10 mg/day and
      Group IV (n:20): HTR + alendronate 5 mg/day. After 12 month treatment, lumbar
      bone mineral density (BMD) significantly increased to 3.6%; 4.1%; 6.5% y 3.1% in
      group I to IV, respectively (p < 0.01; figure 1). Differences among groups do not
      reached statistical significance. The percentage of responders to medication in
      each group was of 68.8%; 92%; 90% y 83%, respectively. Bone mineral density in
      femoral neck (FN) increased with all regimens, though mean values did not surpass
      method variation coefficient. Differences from baseline were statistically
      significant in group I (p < 0.05). The percentage of responders in this region
      was 58.8%; 60%; 62.5% y 45.5%, respectively. Biochemical bone markers (table 2),
      especially urinary pyridinoline and serum osteocalcin, showed a trend in bone
      metabolism inhibition that was more sustained in group III, as show mainly by the
      bone markers pyridinolines and osteocalcin. It is concluded that either single
      therapy with alendronate or estrogen or their combination halted bone loss in
      most patients leading to bone mass gain mainly in lumbar spine in the short term.
      However, bone effects with hormone replacement therapy in association with
      alendronate 10 mg were comparatively major, indicating the potential benefits of
      this regimen in the long term.

PMID- 9567356
TI  - [Clinical, humoral and scintigraphic assessment of a bisphosphonate as potential
      treatment of diaphyseal dysplasia: Ribbing and Cammurati-Engelmann diseases].
AB  - Cammurati-Engelmann's Disease or Progressive Diaphyseal Dysplasia (PDD), is a
      rare autosomal dominant disorder, sometimes non hereditable, which begins in
      childhood, and is characterized by symmetrical excess of osseous apposition in
      diaphysis and metaphysis of long bones. In severe cases skull and vertebrae could
      be involved. Clinically, patients refer limb pain, muscular weakness and atrophy,
      easy fatigability and waddling gait. Later on S. Ribbing described an illness
      that he thought was a separate entity with sclerosis and enlargement of diaphysis
      of femora and tibiae, which begins after puberty, is less extensive, not always
      symmetric and without gait or neurological involvement. Some authors think it may
      be an adult form of the PDD. As no specific treatments are available we report
      one case of each entity, treated with the bisphosphonate pamidronate, by the oral
      route. A white female, 69 years old, with clinic and radiology of Ribbing's
      Disease, had positive scintigraphy in the affected areas and elevated bone
      biochemical markers: Serum alkaline phosphatase (SAP): 57 UKA. Total urinary
      hydroxyproline (THP): 60 mg/24 h. Bone Gla protein (BGP): 40 ng/ml. Considering
      the high bone turnover treatment with oral pamidronate, 400 mg/day plus Calcium
      1g/day was started, dose was then progressively reduced. After two months pain
      almost disappeared, and THP became normal: 14 mg/24 h; with normalization of BGP
      values: 8 ng/ml, and a decrease of SAP: 21 UKA, 99mTc MDP uptake by affected
      bones decreased after 1 year of treatment. Because of these results we decided to
      begin treatment in a white female 17 years old, 32 kg weight, 1.47 m height with
      PDD characteristics and also a high bone turnover (THP: 95 mg/24 h. SAP: 32 UKA).
      After six months of Calcium 1 g/day, given with meals, and oral pamidronate 100
      mg/day, she became painless with normal strength and gait, almost normalization
      of THP (48 mg/24 h). Although a small decrease of SAP, and no charges in
      scintigraphy. These results obtained with pamidronate suggest that it may be
      useful to treat dysplasias with high bone turnover.

PMID- 9567357
TI  - Bisphosphonates: structure-activity relations from a clinical perspective.
AB  - Bisphosphonates, synthetic compounds containing two phosphonate groups bound to a
      central (geminal) carbon (P-C-P) and two additional chains (R1 and R2,
      respectively) bind strongly to calcium crystals, inhibit their growth and
      suppress osteoclast-mediated bone resorption. The availability of two side chains
      allows numerous substitutions and the development of a variety of analogs with
      different pharmacological properties. The R1 structure together with the P-C-P
      are primarily responsible for binding to bone mineral and for the physicochemical
      actions of the bisphosphonates and a hydroxyl group at R1 provides optimal
      conditions for these actions. The R2 is believed to be responsible for the
      antiresorptive action of the bisphosphonates and small modifications or
      conformational restrictions of this part of the molecule may result in marked
      differences in antiresorptive potency. The presence of a nitrogen function in an
      alkyl chain or in a ring structure in R2 greatly enhances the antiresorptive
      potency and specificity of bisphosphonates for bone resorption and most of the
      newer potent bisphosphonates contain a nitrogen in their structure. Recent
      evidence, however, suggests that the whole bisphosphonate molecule is essential
      for antiresorptive action. Thus, although the basic structural requirements for
      bisphosphonate actions have been defined, precise structure-activity relations
      have not been defined yet. These are essential for elucidating their molecular
      mechanism of action and for the rational design of compounds for various clinical
      indications.

PMID- 9567358
TI  - Mechanisms of action of the bisphosphonates.
AB  - Geminal bisphosphonates, usually called bisphosphonates, are synthetic compounds
      characterized by a P-C-P bond. Many such bisphosphonates have been synthesized,
      each of them having its own physicochemical and biologic characteristics. This
      implies that it is not possible to extrapolate from the results of one compound
      to others with respect to their actions. Bisphosphonates can exert
      physicochemical effects very similar to those of polyphosphates, binding to the
      surface of calcium phosphate crystals and inhibiting their formation and
      aggregation as well as their dissolution. Many of the bisphosphonates are very
      powerful inhibitors of bone resorption. This is seen both in normal animals and
      in animals where bone resorption is simulated by various means. Thus, they are
      active in various models of human diseases, such as hyperparathyroidism, tumoral
      bone disease and osteoporosis. They not only prevent bone loss, but actively
      increase bone mass and improve the biomechanical properties of the skeleton. The
      activity varies greatly from compound to compound, the newest bisphosphonates
      being 5,000 to 10,000 times more active than etidronate, the first bisphosphonate
      described. The mechanism of action appears to be complex. It involves: a) a
      direct effect on the osteoclast activity. b) A direct and indirect effect on the
      osteoclast recruitment. The latter is mediated by cells of the osteoblastic
      lineage and involves their production of an inhibitor of osteoclastic
      recruitment. c) A shortening of osteoclast survival by apoptosis. Large amounts
      of bisphosphonates can also inhibit mineralization through a physicochemical
      inhibition of crystal growth. Bisphosphonates are used therapeutically in humans
      to decrease bone resorption, among others in Paget's disease, tumor bone disease,
      and recently osteoporosis. Etidronate is also sometimes used to prevent ectopic
      calcification.

PMID- 9567359
TI  - [Clinical application of bisphosphonate's pharmacokinetic principles].
AB  - Bisphosphonates are a group of osteotropic substances able to modulate bone
      metabolism in different ways. They all display similar pharmacokinetic
      characteristics when administered in proportional dosages and assessed by similar
      methods. With the exception of olpadronate which is soluble in water,
      bisphosphonates have poor solubility, and may easily precipitate in the digestive
      media. In spite of their low digestive absorption (Bioavailability: 0.3-5%), they
      are effectively administered by oral route. Once in plasma they distribute
      rapidly, being uptaked by mineralized tissues, plasma proteins or eliminated by
      renal filtration in few minutes. The fraction retained in bones may be stored for
      long periods (from months up to 10 years depending on the compound) in an
      apparent inactive compartment. The risks of newly released molecules may be
      related to the potency of the drug. Within the clinical range of doses,
      bisphosphonates are not retained in soft tissues. This may explain the lack of
      extraskeletal collateral effects. Plasma blood levels are scarcely related to the
      clinical activity. Therefore, dosage may be guided better by biochemical markers
      of the bone disease than by the standard kinetic variables. On the other hand,
      dose is independent from age and/or body weight. Only renal impairment may induce
      additional dose adjustments.

PMID- 9567360
TI  - [Effects of bisphosphonates on the mechanical efficiency of normal and osteopenic
      bones].
AB  - Bone mechanical competence (stiffness, strength) at organ level is determined by
      mechanical quality (intrinsic stiffness) and spatial distribution (macro
      architecture) of bone material in cortical tissue (in every bone) and trabecular
      network (in vertebral bodies). These properties are inter-related and controlled
      according to mechanical usage by a feed-back mechanism known as mechanostat.
      Therefore, the effects on bone fragility of any treatment should be evaluated
      concerning the way they may have affected bone material or geometric properties
      as well as the mechanostatical interactions between them. Standard densitometry
      does not provide the necessary data, but some alternative methodologies (as
      peripheral quantitative computed tomography, pQCT) are being developed to
      complement or even substitute SPA, DPA or DXA determinations. Bisphosphonate (BP)
      effects on bone biomechanics have been studied only in animal models. Many
      sources of variation of results (type of compound, dose, mode of administration,
      species, race, sex, age, age since menopause, type of bone, remodeling ability of
      the skeleton, endocrine-metabolic status, interactions with other treatments,
      etc.) have been reported. In general terms, BPs are beneficial concerning
      cortical bone strength in purely modeling species (rodents) and trabecular
      strength in remodeling mammals (dogs, baboons). This positive action at organ
      level depends on independent improvements in bone macro-architecture (mainly
      affected by bone modeling) and material stiffness (chiefly affected by bone
      composition and remodeling). On one hand, bone macro-architecture has been
      positively affected by BPs in normal (not in ovariectomy (OX), steroid- or disuse
      induced osteopenic) animals. On the other, bone material quality has been
      improved in the latter but not in the former. Mechanostatic interrelationships
      have been differently affected according to the compound employed. Results
      reported by ours and other laboratories concerning the three derivatives
      available nowadays in Argentina were reviewed and summarized. Pamidronate
      improved small rodents' cortical bone strength and geometric properties at low
      doses but impaired mineralization, material properties and strength at toxic
      doses. In normal, remodeling animals it improved mechanical properties in
      vertebral bodies but not in long bones. It also prevented the negative impact of
      OX-, steroid- or disuse-induced osteopenia in rats by improving bone material
      properties without affecting normal mechanostatic interrelationships. Olpadronate
      exerted positive effects on long-bone strength at any dose in normal rats and
      mice by improving cross-sectional properties and preserving both mineralization
      and material properties. These effects were highly dependent upon bone
      deformability, body weight, and mechanical usage of the limb as an evidence of an
      anabolic interaction induced on bone modeling and mechanostatic
      interrelationships. This compound also prevented the OX- or disuse-induced
      impairment in rat cortical long-bone strength and recovered rat cortical bone
      when given since 3 months after OX by improving only bone material quality. No
      interaction with bone mechanostat was detected in these studies. Alendronate
      effects on bone biomechanics in normal rats and dogs were positive only in long
      treatments. They were highly dependent on body weight of the animals, hence a
      positive interaction with bone mechanostat should be hypothesized. It also
      prevented the negative impact of OX in rat femurs by improving cortical material
      quality with no effect on cross-sectional properties, i.e., exerting an anti
      catabolic interaction with bone mechanostat. The effects of all the three
      compounds were found positive for bone health, yet their mechanisms of action
      varied with type of bone and subject condition. A striking dissociation between
      (positive) effects on bone strength and (variable) effects on bone stiffness was
      repeatedly observed in these studies. Also an enla

PMID- 9567361
TI  - [Preclinical toxicology of bisphosphonates].
AB  - Bisphosphonates regulate bone turnover by inhibiting osteoclastic bone
      resorption. Due to their pharmacodynamic and pharmacokinetic characteristics,
      bisphosphonates have a special pharmacotoxicological profile related to their
      high degree of specificity: low or non-existent distribution in soft tissues and
      strong affinity for calcified tissues. Some general conclusions may be drawn from
      the pre-clinical toxicological studies, whose main aim is to identify the
      toxicity target organ/s and estimate the safety margins of a "prospective
      therapeutic agent" in laboratory animals. They are based on our own results and
      on data from the available literature as regards various bisphosphonates:
      Alendronate, Clodronate, Etidronate, Olpadronate and Pamidronate. Generally, very
      high doses of bisphosphonates are required to produce in different levels and
      incidence various extra-skeletical toxic side effects: local reaction,
      hypocalcemia (and its consequences on the cardiovascular system and the
      possibility of tetany), affection of the dental structures and renal dysfunction.
      Most of side effects may be related to the low solubility in biological fluids,
      the formation of calcium complexes, the potent inhibitory effect of endogenous or
      induced bone resorption as well as to its main excretion pathway. Some other side
      effects (on the eye, lungs and liver), may be related to repeated excessive high
      doses. A safety margin of 200 to 300 : 1 between the "toxic" and
      "pharmacological" doses may be estimated if the total quantity of Olpadronate
      given to various animal species in toxicological studies and in pharmacodynamic
      experimental models (osteopenias due to estrogen deprivation or immobilization
      and retinoid-induced hypercalcemia) is considered. If the toxic doses in animals
      are related to the highest doses suggested for human beings, then the ratio
      increases from 300 to 1000 : 1 depending on the pathology and the route of
      administration. As regards their effect on the bone, experimental data with the
      new bisphosphonates suggest a significant dissociation between pharmacologically
      active doses and those ones producing defective mineralization. The excessive
      inhibition of bone remodelling, due to the use of high doses in normal animals,
      is the natural consequence of the pharmacological effect of this family of
      compounds. A bisphosphonate's toxic potential effect on bone should not be
      evaluated in normal animals but in particular situations with a high bone
      turnover. Furthermore, the doses should be adjusted in order to regulate the
      magnitude of bone remodelling inhibition so as to take it to a normal level
      without totally suppressing it. Potency, safety margins, doses and proper
      administration schemes, should be considered as key elements for the optimum use
      of the therapeutic potentiality of these compounds.

PMID- 9567362
TI  - Use of pamidronate in chronic and acute bone loss conditions.
AB  - Involutional osteoporosis (OP), Osteogenesis imperfecta (OI) and Reflex
      sympathetic dystrophy syndrome (RSDS) are conditions in which an increase in bone
      resorption has been described. It therefore seems logical to prescribe a potent
      inhibitor of bone resorption like pamidronate (APD) in a patient suffering from
      any of these conditions. In our experience, oral as well as intravenous APD
      therapy was able to increase significantly bone mineral density (BMD) in patients
      with OP. This increase was more marked at the lumbar spine than at the proximal
      femur. With cyclical intermittent APD therapy, a plateauing effect in the BMD
      results during the third year appeared. After weaning from APD therapy, a
      remanent effect was observed: no loss of bone apparently occurred for at least
      two years, but the biological remodeling parameters re-increased earlier. The
      protective action on OP fractures has still to be clearly demonstrated, however.
      In children with OI, oral APD therapy has produced a dramatic increase in bone
      mass, without adversely interfering with the growth spur. The effect on fracture
      rate is still debatable in such a protean condition. Intravenous APD administered
      daily for twelve days has provoked a dramatic improvement in patients with long
      lasting RSDS which had resisted to various well-accepted therapies. However, this
      was an open trial, and these favorable preliminary results should be confirmed in
      a double-blind study.

PMID- 9567363
TI  - Oral pamidronate in the prevention and treatment of skeletal metastases in
      patients with breast cancer.
AB  - Bone metastases are common in patients with breast cancer and cause considerable
      morbidity and deterioration of the quality of life. The main pathogenetic
      mechanism is stimulation of osteoclastic bone resorption by factors produced by
      the cancer cells. Pamidronate given intravenously suppresses bone resorption and
      is an effective treatment of malignancy-associated hypercalcemia. Recent data
      indicate that it can also reduce skeletal morbidity in normocalcemic patients
      with breast cancer and osteolytic metastases. In a series of studies we examined
      the long-term efficacy of oral pamidronate in the prevention and treatment of
      skeletal metastases in patients with breast cancer. In patients with bone
      metastases oral pamidronate given for a median period of about 20 months reduced
      significantly skeletal morbidity and had a favourable effect on selective aspects
      of the quality of life of the patients. Treatment did not alter the radiological
      course of the disease or the overall survival of the patients. In contrast, oral
      pamidronate given to patients with advanced breast cancer but no demonstrable
      bone metastases did not prevent or delay the appearance of the first clinical or
      radiological manifestation of bone metastases. This treatment is therefore very
      effective in patients with established metastatic bone disease. More studies are
      needed to define the place of pamidronate (and of other bisphosphonates) in the
      prevention of bone metastases in patients at risk.

PMID- 9567364
TI  - [Tolerability of oral bisphosponates in patients with osteoporosis and other
      osteopathies].
AB  - Oral nitrogen containing bisphosphonates (NCB) are effective drugs to inhibit
      bone metabolism turnover in osteoporosis and other bone diseases.
      Notwithstanding, some digestive disturbances create concern on the long term
      acceptance of the oral route. Side effects are mainly caused by low absorption
      and poor solubility in digestive content. Therefore the compound may precipitate
      and irritate the mucosas. Furthermore, the administered amount of a particular
      molecule, its intrinsic potency to irritate digestive walls and the degree of
      exposition to such sensitive tissue are other facts that combined, may determine
      the clinical tolerability. Thus, a single factor cannot predict the clinical
      tolerability. Pamidronate, alendronate and olpadronate are the main NCB under
      clinical usage. Alendronate is 10 times more potent than pamidronate but
      possesses a similar slight solubility (2.4 vs 3.0% W/V respectively). It also
      seems to be more (3 times fold) ulcerogenic in experimental assays. The current
      available pamidronate formulation protects from esophagus and gastric exposition.
      Up to now and until randomized clinical trials be performed the selection of the
      most tolerated aminobisphosphonate in clinical practice will depend on the
      interplay of many factors (table 1 shows a hypothetical view). Moreover,
      different patients may react dissimilarly depending on their sensitivity to a
      particular factor. Olpadronate is free-soluble (24% W/V), almost equipotent with
      alendronate (figure 1) and seems to lack relevant irritation potential, but
      clinical data is on its early phases and is still not available. Micronization of
      the bisphosphonate preparation may be of help to improve tolerability as shown
      with newer pamidronate oral formulations. The current clinical published data
      shows more or less the same safety profile for pamidronate (only when enteric
      coated capsules are used) as alendronate, with more than 90% of patients
      complying with long term treatments. Anyway the trials are not entirely
      comparable as said before. Some other pamidronate formulations proved to be
      intolerable and have not been accepted. Identifying the many factors of oral
      NCB's digestive tolerability may help with their clinical management. And in
      those countries where the two compounds are available they may alternatively be
      used in the sensitive patients. Finally, extra-digestive side effects, not
      commented in this article, should also be weighted when selecting a
      bisphosphonate.

PMID- 9567365
TI  - Osteoporosis treatment: quo vadis? (A brief overview).
AB  - What we formerly called osteoporosis includes four conditions with an osteopenia:
      A) osteopenias usually due to mechanical disuse, where injuries cause fractures,
      and in limb bones more than the spine; B) osteopenias with such fragile bone that
      normal activities instead of injuries can cause fractures and/or bone pain, and
      in the spine more than limb bones; C) a group that combines features of (A) and
      (B); D) temporary osteopenias while major fractures, burns or other injures heal.
      If belatedly, we now realize our past failure to view those conditions as
      separate entities compromised many past studies of the prevalence, diagnosis and
      ways to prevent and cure each of them. That failure also compromised many past
      explanations of the nature, pathogenesis and natural course of "osteoporosis",
      and much of the related research. This caused some confusion as well as
      controversies about illusory instead of genuine issues. Controlling existing
      osteoblasts and osteoclasts with drugs has not prevented or cured those
      conditions. That will require controlling the modeling drifts and remodeling BMUs
      that create those cells. Modeling can increase bone mass and strength, remodeling
      can conserve or reduce them, and neither can provide the other's functions.
      During normal mechanical usage modeling is OFF and remodeling works in its
      "conservation mode" to keep existing bone. In disuse, modeling stays OFF while
      remodeling works in its "disuse mode" to remove bone and cause an osteopenia.
      Most natural nonmechanical agents (Table 1) can help or hinder those mechanical
      responses, but cannot duplicate or override them. Wrist and hip fractures from
      falls cause the most serious problems associated with these conditions. Those
      fractures begin in the cortex of epiphyseal-metaphyseal regions of limb bones.
      They never begin in trabecular bone and rarely in the shafts of long bones. They
      never begin in the trabecular bone and rarely in the shafts of long bones. Since
      a bone's strength depends on its shape and size (architecture) as well as on the
      amount of bone in it (bone mineral "density" and content), treatments intended to
      prevent or cure these conditions should strengthen the above cortex, and
      absorptiometric studies should begin to account for both bone architecture and
      bone tissue content. "Bone anabolic" agents (parathyroid hormone and some
      prostaglandins) can make modeling add bone to normal and osteopenic skeletons,
      but when the treatment stops remodeling begins removing that bone.
      "Antiremodeling agents" (including estrogen and many bisphosphonates) can make
      remodeling tend to keep existing bone, but when such treatments stop remodeling
      usually resumes removing bone. Combining anabolic agents with antiremodeling
      agents offers an exceptionally promising prospect of effective prevention and
      cure of the above osteopenias. Practical problems make this approach not yet
      ready for human use, but it soon could be.

PMID- 9567366
TI  - Histochemical staining of bone aluminum: comparison of aluminon and acid
      solochrome azurine and their correlation with bone aluminum content.
AB  - Aluminum (Al) may be a pathogenic factor in dialysis associated osteodistrophy.
      Aluminon and Acid Solochrome Azurine have been used for the detection of Al
      deposits in bone. We compared Aluminon and Acid Solochrome Azurine stains in
      normal (N) and uremic (U) rats. Both received intraperitoneal injections of
      aluminum chloride (AlCl3), until a cumulative dose of 5 mg/Al (NAL5; UAL5) or 30
      mg/Al (NAL30; UAL30). The control groups received an equal volume of distilled
      water by means of intraperitoneal injections. Histomorphometric analysis showed
      that formation parameters (osteoid volume-OV/BV and osteoid surface-OS/BS), were
      significantly greater in the uremic groups than the control groups. In addition,
      the aluminum intoxication increased these values. When we compared the aluminum
      deposits in the undecalcified bone detected by both staining methods, we observed
      that Acid Solochrome Azurine was more sensitive than Aluminon in the normal renal
      function group and uremic treated with 5 mg of AlCl3. All our results were
      compared with atomic absorption spectrophotometry, showing that Al content
      presented a positive correlation with Aluminon stain in U and N rats,
      nevertheless it was not observed using Acid Solochrome Azurine stain. We conclude
      that histochemistry is important in diagnosing and monitoring aluminum bone
      disease.

PMID- 9567367
TI  - [Surgical treatment outcome of hemorrhoidal in 475 patients].
AB  - Despite feared by patients and reserved for the minority of patients suffering
      from hemorrohoids, hemorrhoidectomy remains as the most effective approach to
      this condition. To analyse results from 475 hemorrhoidectomies performed at
      University of Sao Paulo Hospital das Clinicas between 1984 and 1995, a
      retrospective chart review regarding gender, age, associated anorectal
      conditions, surgical technique, complications and their management and follow-up
      was addressed. Two hundred and seven (43.6%) were male. Age between fourth and
      sixth decades were observed for 70.8%. Associated anorectal conditions were
      diagnosed in 18.9%. Chronic anal fissure was the commonest one. Milligan-Morgan
      operation was performed in the majority of patients (91.2%) and Ferguson
      technique in 6.7%. There were no intraoperative complications postoperative
      complications occurred in 38 (8%) patients regardless of employed surgical
      technique. Urinary retention was the commonest postoperative complication. Mean
      follow-up was 5.8 years for 70% of patients. Surgical hemorrhoidectomy remains as
      a treatment with excellent results in the management of hemorrhoid disease for
      selected patients. Produces erradications of the disease in all cases in spite of
      low morbidity.

PMID- 9567368
TI  - [Technical and histological standardization of experimental colitis with
      trinitrobenzenosulfonic acid (TNBS)].
AB  - Attempts to reproduce inflammatory colitis have created many experimental models.
      Since the pioneer work of Morris et al. (1989), trinitrobenzenosulfonic (TNBS)
      solutions have been used with different dosages. The aims of this work were
      standardize the induction of colitis, evaluate the clinical and intestinal
      effects of different doses and verify the reproducibility of the intestinal
      inflammatory process. Wistar rats were inoculated endo rectally with 2.5 ml
      solutions of different concentrations of TNBS and ethanol, and the rats were
      sacrificed after 14 days. According to the solution concentrations of TNBS (mg)
      and ethanol (%), six groups of animals were established: Control (saline), 30
      mg/30%, 30 mg/40%, 30 mg/50%, 50 mg/10% and 50 mg/30%. Statistical analysis of
      food ingestion showed no differences between groups (p = 0.247). The 30/50 group
      presented greater weight loss when compared to 50/10 and 50/30 groups (p =
      0.012). Groups 30/50 and 30/40 showed greater degrees of macroscopic lesion than
      control and 50/10 group (p < 0.05). Histologic lesion was not uniform to all rats
      regardless of the solution employed. Group 50/10 presented the less severe
      histologic alterations; on the other hand, 30/40 and 30/50 groups had important
      changes on mucosal thickness, on vascularization and ulceration. The authors
      conclude that experimental colitis with TNBS 1) cause intestinal lesions that are
      not uniform to all animals, although they may be reproduced in many of them; 2)
      with the same doses of TNBS, the increase in ethanol concentrations leads to a
      greater inflammatory process, intestinal thickness, vascularization, abscess
      formation and intestinal ulceration; 3) 50/10 and 50/30 solutions make less
      severe lesions when compared to 30/40 and 30/50 solutions; 4) 30/50 solution was
      the best one, as it produces inflammation 90% of the animals, increases in wall
      thickness in 50%, abscess in 70% and ulceration in 38%.

PMID- 9567369
TI  - [X-linked agammaglobulinemia in nine patients: review of the literature].
AB  - The X-linked agammaglobulinemia (XLA) is a rare immunodeficiency, characterized
      by absence or accentuated diminuition of all the isotypes of serum
      immunoglobulins and greater susceptibility to infections, mainly after the sixth
      mouth of life. The authors present nine patients bearers of XLA, with recurrent
      infectious processes (pneumonias 7/9, otitis 7/9, sinusitis 5/9, sepsis 5/9,
      diarrheas 3/9, infectious arthritis 3/9, meningitis 3/9, pyodermitis 3/9, viral
      encephalitis 1/9), with the beginning of symptoms on average in a nine months
      life. The laboratory examination showed absence of antibody response, with normal
      cellular immunity. The patients received immunoglobulin with control of the
      infectious processes. Five children received prophylactic antibiotic therapy for
      sinusitis control. The precocious diagnosis of XLA is of extreme importance, with
      institution of therapy with intravenous immunoglobulin for reduction in
      infectious process occurrence and complications, besides improving the patient's
      life quality.

PMID- 9567370
TI  - [Evaluation of the eventual activity of cyclosporin A in preventing the
      transmission, by blood transfusion, of Trypanosoma cruzi infection].
AB  - Cyclosporin A has activity "in vitro" against trypomastigotes of Trypanosoma
      cruzi. We tried to evaluate, in an "in vitro" model, using variable
      concentrations in whole blood contaminated with known numbers of parasites and
      injecting this blood after a two hour incubation period in mice if it was
      possible to prevent infection. In this model the drug, in the concentrations
      used, was unable to prevent infection.

PMID- 9567371
TI  - [Gallbladder emptying evaluation in chronic calcifying pancreatitis, by means of
      a scintilographic study with Tc-99m DISIDA].
AB  - The aim of this study was to analyze the gallbladder motor function in chronic
      pancreatitis (CP) patients. Gallbladder emptying was evaluated in 11 patients,
      without and with addition of pancreatic extract and in ten controls. The results
      were compared and analyzed statistically. The ejection fraction (EF) of the
      gallbladder (GB) at 30, 45 and 60 minutes were calculated by using Tc-99m DISIDA
      scintigraphy. The EF of GB at 60 minutes was significantly higher in the controls
      when compared to patients, although the results between patients were similar
      without and with addition of pancreatic extract. The results suggest that the
      delay in the GB emptying does not depend on the eventual alteration in the
      intestinal phase of the vesicular stimulation, but it probably results from a
      mechanic factor, which depends on the chronic pathological process located in the
      head of the pancreas.

PMID- 9567372
TI  - [Antibiotic prophylaxis in oncologic surgery].
AB  - Perioperative antibiotic administration can decrease surgical morbidity, shorten
      hospitalization, while lowering the overall costs attributable to infections. Its
      use in surgery is widespread and often inappropriate. In this study, the authors
      evaluate the guidelines for selection and use of prophylactic antibiotics in
      surgical cancer patients at the Hospital of Cancer in Rio de Janeiro, Brazil.
      During 36 non-consecutive months, 1681 cancer patients submitted to surgical
      procedures were prospectively followed-up by members of the Hospital Infection
      Control Committee. The overall surgical site infection (SSI) and mortality rates
      were 17.7% and 4.8% respectively. Prophylactic antibiotics were used in 1262
      elective surgeries (75.1%), and their use was not considered to be in accordance
      with the recommended protocol in 37.6% of the cases. The inadequate antimicrobial
      prophylaxis resulted in higher incidence of SSI than did prophylaxis in according
      to the protocol (21.7% vs. 16.4, Relative Risk 1.32; 95% Confidence Internal 1.05
      1.67; p0.01). This study calls the attention for the need of a more strict and
      determined educational program in order to provide mechanisms for an adequate
      administration of prophylactic antibiotics to patients submitted to high-risk
      surgeries.

PMID- 9567373
TI  - [Reconstruction of a thoracic wall defect using a flap of omentum obtained by
      laparoscopy].
AB  - Reconstructive of complex chest wall defects following infected sternotomy
      represents a surgical challenge. Several options were described for these defects
      reconstructions, using muscles flaps and omentum which provided obliteration of
      dead space and coverage. We present a reconstruction of a major chest and
      abdominal wall defect in a 62-year old patient, who had mediastinitis,
      osteomyelitis and necrosis of sternum after myocardial revascularization. The
      pectoralis major was used unsuccessfully, with total loose of the flap. After
      wound failure, a flap of omentum based on the left gastroepiploic vessels was
      obtained by a laparoscopic surgery, with no complication. The omentum was
      translocated through the defect that reached the abdominal wall covering the
      defect and allowing the use of split-thickness grafts. The laparoscopic procedure
      showed advantages over the laparotomy in the management of omentum, with the same
      results in the reconstruction of the defect added the advantages of a minimal
      invasive procedure, mainly in patient with bad clinical conditions.

PMID- 9567374
TI  - [Evaluation of the degree of client satisfaction with ICHC/PAMB regarding
      secretarial and medical assistance].
AB  - This survey was intended to evaluate the degree of satisfaction from clients of
      Predio dos Ambulatorios do Instituto Central do Hospital das Clinicas concerning
      waiting time for appointment, kind of reception and quality of attention by
      secretaries and doctors. It was also intended to evaluate the interest people
      have in the video system, that has monitors in the majority of the great waiting
      rooms, as well as what people think about Instituto Central do Hospital das
      Clinicas as an institution.

PMID- 9567375
TI  - [Profile of medical schools of the State of Sao Paulo, Brazil, in 1996].
AB  - The author examines different aspects of medical schools located in the region of
      Sao Paulo State (Brazil). There are 19 schools corresponding to 23% of the total
      number of medical schools in Brazil. The analysis includes elements about
      students and teachers, including their number and academic titulation; elements
      about teaching-learning process are also evaluated. An important contribution is
      the comparative analysis of the curricular evolution from 1986 to 1996.

PMID- 9567376
TI  - [Revista Medica de Chile: a long and beautiful educational task].
AB  - Revista Medica de Chile is one of the oldest medical journals in the world. Since
      its foundation in 1972, it had an educational character. Its successive editors
      and members of editorial committees have been distinguished clinicians,
      investigators and teachers. The diffusion of this journal among physicians and
      students for more than a century, renders it as a pioneer form of continuous
      distance education and could be considered as a "silent and peaceful campus".
      Through the years, this journal has coped with the progress in medical and
      biological knowledge,the perfecting of graphic arts and editorial processes and
      the development of computing. It has improved its management and professionalized
      the editorial process. In the near future, this last aspect will need further
      improvements due to its increasing complexity. The journal adheres to
      international publication norms for scientific manuscripts and is connected to
      international associations of medical journal editors. The editors have assumed
      the professional and ethical responsibility of controlling that publications
      provide valid information in a language intelligible for most readers. This
      compromise implies an independent work and the rejection of any form of undue
      pressure. We can state that Revista Medica de Chile, as a whole, is a historical
      document and that its pages reflect the capacity and intelligence of several
      generations of Chilean physicians.

PMID- 9567377
TI  - [125th anniversary of Revista Medica de Chile].
AB  - The first issue of Revista Medica de Chile was printed in July, 1872. Since then,
      it has been published monthly, interrupted only for a few months during a Chilean
      civil war (1891). This medical journal has been devoted mainly to clinical topics
      in internal medicine, but currently it includes an increasing proportion of
      research papers in other biomedical and preclinical subjects. This journal is
      included in the most important international indexes of biomedical publications.
      Most issues cover also medical education, public health, the ethics of clinical
      and experimental research, medical administration and the history of medicine.
      The evolution of medicine in Chile along 125 years is clearly reflected in the
      contents of this journal. Revista Medica de Chile is one of the oldest medical
      journals in the world, particularly among those published in Spanish, and a top
      ranking biomedical publication in Chile.

PMID- 9567378
TI  - [A tribute to German Schneider, MD, first editor of Revista Medica de Chile].
AB  - German Schneider was born in 1820 in Magdeburg, Germany, and graduated as M.D. at
      the University of Bonn. In 1848, caught by the political and intellectual
      reformist movement in Europe, he was exiled in Paris. As part of a large group of
      German immigrants, he arrived in Valdivia, Chile, in 1851. Later on he moved to
      Santiago and in 1871 he was nominated Professor of Clinical Medicine at the
      University of Chile school of Medicine. An active participant in the academic
      activities organized by Sociedad Medica de Santiago (a scientific society that
      evolved into the chilean Society of Internal Medicine) he was the leader of a six
      men team who founded Revista Medica de Chile, in 1872. As first Editor of this
      medical journal, he established the basis for its continuous success and devotion
      to medical progress and education. Dr. Schneider died in 1884, leaving several
      distinguished pupils who followed his path, and a medical journal that now stands
      as one of the oldest in the world.

PMID- 9567379
TI  - [History of Revista Medica de Chile from its creation in 1872 until 1997].
AB  - Revista Medica de Chile, official journal of Sociedad Medica de Santiago, was
      founded in 1872 and has appeared uninterruptedly until today. Its aim, since its
      creation, has been the diffusion of scientific knowledge of Chilean physicians
      through original contributions, medical review articles and information about
      foreign medical literature. During the first 50 years of existence, physicians of
      medical and surgical specialties collaborated with articles, butafterwards, its
      main interest was oriented towards internal medicine. Its preoccupation for
      public health has been constant. Between 1930 and 1950, the interest in
      internists to divulge national clinical investigation gave a great impulse to
      this journal. Two important design modifications in 1958 and 1973 allowed the
      magnification of its information range. The incorporation of peer review of
      manuscripts in 1973 was an important achievement. Since its foundation, Revista
      Medica de Chile has been the principal written source of postgraduate training in
      our country.

PMID- 9567380
TI  - [A scientometric radiography of Revista Medica de Chile].
AB  - In the context of a festschrift to commemorate the 125th anniversary of the
      Revista Medica de Chile, "radiography" of the journal has been depicted using
      several scientometric indicators. Among the mainstream journals in the category
      of Medicine, General & Internal and taking into account the wide editorial
      coverage and the language of the publication that fulfills the need for the
      required social appropriation of science that the country requires, the Revista
      Medica de Chile portrays healthy and quite relevant. Among the articles published
      between 1981 and 1995, some concerning public health have reached, particularly,
      an impact which surpasses their mean expected citation rate.

PMID- 9567381
TI  - [Essential aspects of the reorganization of medical education at the University
      of Chile School of Medicine].
AB  - The Medical School of the University of Chile is enforcing deep transformations
      in its curricular setting, to cope with the physician model of the next century.
      It is following the universal trends that look for new objectives, methodologies,
      scenarios and resources in medical teaching. These goals should be accomplished
      very soon, allowing the School to be in the lead of curricular transformations.
      These changes have overflowed the limits of curricular renovation and a process
      of institutional reorganisation is aiming to increase its efficacy and yield. The
      bases of this reorganisation are the search for excellency, the renovation of
      academic staff with the incorporation of better trained professionals, the
      integration of basic and clinical disciplines in coherent programmatic proposals
      and the configuration of structures to organise and articulate medical knowledge.
      Optimisation of education has also extra-institutional implications with the
      establishment of accreditation systems for professionals and educational
      institutions. These systems are mandatory world wide and guarantee the capability
      of educational institutions and their products. The School of Medicine is
      committed in this achievement along with the Association of Medical Schools and
      The Superior Education Council.

PMID- 9567382
TI  - [Aims and objectives of medical education at the Medical School of Universidad de
      Concepcion].
AB  - Ultimately, medical education is oriented world wide towards the promotion and
      improvement of people's health and the promotion of welfare, along with other
      organisations. The development of science, technology and instructional
      resources, the concerns of the community and nations about health matters and
      their health care policies, require a new approach towards medical education.
      Universities must be aware of these new demands, that must be taken into account
      in medical education. New medical curricula should consider the new scenarios in
      which the process of health and disease takes place and the new participants in
      such process, the need for technological offices with trained and committed
      personnel devoted to its design and the need to be permanently evaluated.

PMID- 9567383
TI  - [Undergraduate curriculum reform at the Pontifical Catholic University Medical
      School: aims, methodology and advance status].
AB  - The Medical School of the Pontifical Catholic University is devoted to a reform
      process aiming to adequate undergraduate training to scientific, technological,
      cultural and social changes in medical practice in Chile and to incorporate novel
      teaching methodology. One of the main modifications is the change of the
      resulting professional from "a general physician capable of resolving most
      medical problems of rural or urban populations" to "a physician with a solid
      general training but qualified for a subsequent specialization". This requires
      curricular flexibility to obtain different professional profiles. Other important
      changes are a reduction in curricular contents and their vertical and horizontal
      integration, modernization of teaching methodologies with the incorporation of
      computing techniques and problem oriented teaching and the incorporation of new
      subjects such as molecular biology, clinical genetics, health economics. To
      achieve these objectives, a semi-flexible curriculum was devised, the curricular
      mesh has been modified extensively, an outpatient and a nine months elective
      internship were added. Most modifications have been implemented, remaining
      changes in 4th and 5th years. These changes required a reorganisation of academic
      structure, the use of new selection, training and perfecting criteria for
      teachers, better salaries for outstanding professors and improvement of teaching
      infrastructure. This reform must be seen as a medium term integral change in the
      context of an integral academic development plan.

PMID- 9567384
TI  - [Aims and objectives of medical training at the University of Valparaiso].
AB  - The Medical School of the University of Valparaiso was founded thirty years ago
      aiming to produce a physician considering the health needs of the population and
      with a solid humanitarian training. The epidemiological, demographic and
      scientific changes of the last decades prompted the introduction of modifications
      in the curriculum such as using problem oriented active learning, incorporation
      of new subjects such as geriatrics, labour medicine and trauma and training in
      communication skills. The curricular mesh will be modified to allow an efficient
      vertical integration of educational contents, which will be delivered
      sequentially during the different years of the career. The internship, as a
      crucial part of the career, has incorporated outpatient clinical practice, has
      emphasized preventive medicine and has stimulated active learning through
      research projects and active reviews of specific issues. These changes will
      require cultural changes of professors and students and more resources that are
      difficult to obtain.

PMID- 9567386
TI  - [The School of Medicine of the Universidad de La Frontera].
AB  - The School of Medicine of Universidad de La Frontera is the result of a tight
      relationship between teaching and patient care. Its recent development is based
      on the strengthening of international bonds. Curricular innovation is an
      important accomplishment, mandated by the strategic setting up of its academic
      corps. The aim of undergraduate teaching is to train health professionals able to
      successfully face prevalent health problems, with health team management
      capabilities, that work in close relationship with the community, with continuous
      educational, research, communicational and learning skills and with a solid
      ethical and humanitarian education. Student based education using priority health
      problems as models, small group tutorials and community training are the bases of
      medical training for the next century.

PMID- 9567385
TI  - [The Universidad Austral de Chile Medical School: a regional commitment].
AB  - The Universidad Austral de Chile Medical School was created in 1966. Its general
      goal was to train a general physician with capacities to integrate biological,
      psychological and social issues, to deal with prevalent diseases as well as with
      the non referable casualties, to analyze health situations and to manage health
      teams. From its beginning, it incorporated anthropological and the public health
      contents to medical curriculum. Moreover, the formal teaching formation was
      reduced to 5 years, increasing the internship cycle to 2 years, with an important
      practice on primary health care in regional hospitals, that included a research
      project on health administration. A revision of the School curriculum showed the
      need of a better horizontal and vertical integration of medical education.
      Consequently, global courses were organized to gather knowledge that, until now,
      was delivered in a fragmented form. Our Medical School has a major impact in the
      southern region of the country and over 60% of its graduates have settled in this
      zone, improving its physician/inhabitant relationship and the number of
      specialists.

PMID- 9567387
TI  - [The School of Medical Sciences of the University of Santiago de Chile].
AB  - The Medical Sciences School of the University of Santiago de Chile, is an
      institution inserted in the occidental culture and therefore on its conceptions
      and traditions. It subscribes the Principles defined in the Universal Declaration
      of the Human Rights of the United Nations and especially the importance of the
      human person, as an entity irrepetible, different to others. The human rights are
      over the institutions, the society and the laws of science. The Faculty considers
      the family as the cell or natural and fundamental element for the development of
      the human being in the society. It defines its historic mission as the search of
      the truth and the achievement of a society in pro of the welfare and health of
      the people in a frame of excellence, justice, humanism, efficiency and
      participation. As an expression of the cultural patrimony it should create and
      transfer knowledge. As guarantor of the ethical principles it should protect the
      dignity that emanates from the transcendent nature of the person and its moral
      principles and therefore its right to life, justice, freedom, equality, health,
      education, and happiness. As a paradigm of progress it must be involved in
      modernization and should impulse the development. As an entity committed with
      Society it should participate in the search of solutions for politics and
      programs looking for a higher level of life and a better model of health. The
      profile of our graduated students will identify them due to their profound spirit
      of welfare of the person, his family, his community, ethical sense, solidarity,
      justness and humanity, their orientation to the community and the environment
      with a solid professional formation in the strategy of Primary Health Care. They
      will provide education in health for the whole family in order to improve a
      better way of life. They will be trained to detect and solve the risks of
      individual, communities and environment. Research is also a priority of the
      Faculty in order to contribute to solve the problems of health of the Nation,
      since there is no development without education and there is no education neither
      development without health. For the Faculty the achievement of these purposes is
      mandatory and we will make them reality through the Prometeo Project 1997-2001.

PMID- 9567388
TI  - [Present and future of internal medicine].
AB  - To mention the crisis of Internal Medicine has become a commonplace, that is
      extremely wrong, because Internal Medicine is stronger than ever, with many
      recent and important contributions like randomised clinical trials, metaanalysis,
      evidence-based diagnosis, cost-benefits analysis, etc. We consider as Internists
      the General Internist, the sub-specialist and the primary care physician. Among
      them, it is the General Internist who needs to redefine his working areas, that
      are progressively moving from the hospital into ambulatory care. Internal
      Medicine is stretched by 3 strong vectorial forces: 1. Its own development and
      technological progress. 2. Economical factors trying to limit increasing costs.
      3. Social forces demanding a better quality of care Internal Medicine shall need
      to equilibrate all these forces and be prepared to solve future challenges such
      as demographic changes, including an ageing population, the compression of
      morbidity, increasing demands of better care and quality of life, contemption of
      excessively high costs and now technical and ethical problems. The internist
      should be the best prepared specialist to cope with these challenges; but to
      better assume them, deep changes in pre and post graduate medical education are
      needed.

PMID- 9567389
TI  - [Is there a relationship between parent's short height and their children's?
      Social interclass epidemiologic study].
AB  - BACKGROUND: Stunting is a prevalent problem in developing countries and may
      affect up to 50% of school age children. AIM: To search for a relationship
      between the short stature of school age children of opposing socioeconomic levels
      and that of their parents. SUBJECTS AND METHODS: One thousand, eight hundred and
      forty two children of low socioeconomic level and 2,770 children of high
      socioeconomic level were initially measured. Those with a z score for height
      below -1 were selected (251 of low socioeconomic level and 157 of high
      socioeconomic level) and the height of their parents was measured. RESULTS:
      Mothers and fathers of low socioeconomic level were 6.1 and 7.4 cm shorter than
      their counterparts of high socioeconomic level. The z score for height of low
      socioeconomic level children was significantly better than that of their parents
      and the relative risk for stunting was 2 when one of the parents had a short
      stature. Among children of high socioeconomic level, the relative risk of
      stunting was 4.8 and 11, when the mother or the father had a short stature,
      respectively. CONCLUSIONS: The better height adequacy of low socioeconomic level
      children, compared to their parents, suggests that the new generations are
      growing better than their ancestors. Among children of high socioeconomic level,
      whose growth potential is fully expressed, the parents height is a good predictor
      of stunting.

PMID- 9567391
TI  - [Copper intake and blood levels as risk factors for atheromatous disease].
AB  - BACKGROUND: Copper is part of antioxidant enzymes and could have a cardiovascular
      protective effect. A higher cardiovascular risk has been associated with high as
      well as low plasma copper levels. AIM: To search for differences in copper intake
      and plasma levels between patients with coronary artery or cerebrovascular
      diseases and normal subjects. PATIENTS AND METHODS: Zinc and copper intake,
      plasma levels and serum lipid levels were measured in 20 patients with
      cerebrovascular disease, 20 patients with an acute myocardial infarction and 40
      subjects hospitalized for elective surgery, that served as controls. RESULTS:
      Copper and zinc intake was below recommended allowances in all subjects. Serum
      zinc and copper levels did not differ in the three study groups. In patients with
      myocardial infarction a weak correlation was found between serum copper and total
      cholesterol (r = 0.24; p < 0.05) and LDL cholesterol (r = 0.31; p < 0.05).
      CONCLUSIONS: No differences in copper levels were found in subjects with
      atherosclerosis and controls. The correlation between serum copper and
      cholesterol deserves further investigation.

PMID- 9567390
TI  - [Immune response against modified low-density lipoproteins in patients with non
      insulin-dependent diabetes mellitus].
AB  - BACKGROUND: Diabetes mellitus is a risk factor for atherosclerosis. Low density
      lipoproteins are considered a key factor in the formation of atheroma and the
      immune system has an important contribution to this process. AIM: To quantify the
      immune response against modified low density lipoproteins in patients with non
      insulin dependent diabetes mellitus. MATERIAL AND METHODS: LDLs obtained from
      blood of healthy subjects, were glycated or altered with malondialdehyde and used
      as antigens. Serum autoantibodies against these LDLs were measured by ELISA in 22
      patients with non insulin dependent diabetes mellitus aged 46 to 67 years old and
      13 healthy controls aged 41 to 65 years old. Basal and LDL stimulated tumor
      necrosis factor a production in vitro, by peripheral leukocytes of diabetics and
      controls was also measured. RESULTS: The ratio of glycated LDL/native LDL
      antibodies was higher in diabetics than in controls (9.37 +/- 2.72 and 0.41 +/-
      0.11 respectively p < 0.05) and the ratio of MDA modified LDL/native LDL
      antibodies was not significantly different (8.64 +/- 3.83 and 2.14 +/- 1.26
      respectively, NS). Tumor necrosis or production by leukocytes was higher in
      diabetics than in controls in basal conditions (53.3 +/- 15.3 and 26.9 +/- 14.7
      arbitrary units (a.u.) respectively), when stimulated with native LDL (46.5 +/- 5
      and 24.3 +/- 9.4 a.u. respectively), when stimulated with malondialdehyde
      modified LDL (50 +/- 16.2 and 24.4 +/- 7.7 a.u. respectively) or when stimulated
      with glycated LDL (38.3 +/- 8.8 and 14.4 +/- 7.5 a.u. respectively). CONCLUSIONS:
      Diabetic patients have an enhanced immune response against low density
      lipoproteins, factor that could contribute to the accelerated atherogenesis of
      this disease.

PMID- 9567392
TI  - [Twelve-year trends of hip fracture rates in Chile. Is there a relationship
      between their increase and population aging?].
AB  - BACKGROUND: Epidemiology of osteoporosis is assessed measuring bone density or
      measuring the rates of bone frailty-related fracture rates. Of these, the most
      important are hip fractures, that markedly increase after 65 years of age. AIM:
      To measure the incidence of hip fractures in Chile from 1982 to 1993. MATERIAL
      AND METHODS: All hospital discharges that occurred in Chile from 1982 to 1993
      were analyzed, looking for the diagnosis of hip fracture. National censuses in
      the same period were also analyzed searching for possible changes in the age
      structure of the population. Fracture rates were analyzed for three age groups,
      and changes along the years were calculated correlating the rates with the number
      of the year. RESULTS: In the twelve year period, women aged 55-64 years old had a
      correlation of 0.32 (NS), women aged 65-74 years old had a correlation of 0.58
      (NS) and women aged over 75 years old had a correlation of 0.95 (p < 0.001). This
      age group corresponded to 2.01% of the whole population in 1982 and to 2.52% in
      1993. The mean age of the group increased from 80.7 to 80.9 years in the same
      lapse. CONCLUSIONS: Fracture rates increased in the 12 years period studied,
      specially among women older than 75 years old. During the same period the
      proportion of people over 75 years old also increased, but there was only a
      slight increase in its mean age. Thus, the increase in fracture rates is
      disproportionate to population aging and could be related to changes in
      lifestyles.

PMID- 9567393
TI  - [Intrasphincteric injection of botulinum toxin in patients with esophageal
      achalasia].
AB  - BACKGROUND: Intrasphincteric injection of botulinum toxin (BoTx) has demonstrated
      to be effective in the short-term treatment of achalasia. AIM: To assess the
      efficacy, safety and long-term outcome of BoTx injection into the lower
      esophageal sphincter (LES) of patients with achalasia. PATIENTS AND METHODS:
      Eight patients received 80 units of BoTx. Assessment of response was based on
      changes in the symptom scores (0-9) and esophageal manometric studies. RESULTS:
      Six out of 8 patients (75%) had sustained clinical improvement after therapy.
      This effect was maintained for a mean time of 17.8 months. The symptom score
      decreased from a mean of 6.7 to 0.5 (p < 0.01) and after treatment, LES pressure
      decreased from 63 to 25.5 mm Hg (p = 0.07). There were no serious adverse
      effects. Five of the six responders have relapsed. Two of these patients received
      a second BoTx injection with satisfactory results, two went to surgery and one
      refused other type of therapy and died of pneumonia. CONCLUSIONS:
      Intrasphincteric BoTx injection is a simple, safe and effective method of
      treatment in patients with achalasia, with a duration of response averaging 1.5
      years. Its use may be suggested in some patients with high surgical risk and
      those who refuse a more invasive therapy. It is also useful in malnourished
      patients to attain an adequate nutritional status before surgery.

PMID- 9567394
TI  - [Clinical and epidemiological study of blood donors seropositive for Trypanosoma
      cruzi].
AB  - BACKGROUND: The prevalence of positive antibodies for Chagas disease in a blood
      bank of a public hospital in Santiago is 1.2%. These positive individuals should
      be informed about their condition and further studied. AIM: To perform a
      serological confirmation, an epidemiological and clinical assessment of blood
      donors seropositive for Chagas disease in a blood bank of Santiago. SUBJECTS AND
      METHODS: One hundred eleven seropositive donors, detected between 1994 and 1996,
      were studied. Serological reactions were confirmed with ELISA and indirect
      immunofluorescence reactions. Those confirmed as positive were subjected to a
      clinical-epidemiological questionnaire, physical examination, EKG and barium
      enema or swallow according to symptoms. RESULTS: Seventy individuals were
      confirmed as positive for Chagas disease. Most of them lived at least once in an
      endemic zone for Chagas disease or in a sun-dried clay brick house. Forty-percent
      of individuals knew reduviid bugs and 14% had been bitten by these insects.
      Twenty six percent of these subjects had an abnormal EKG (61% with bradycardia).
      No digestive diseases attributable to Chagas disease were detected. CONCLUSIONS:
      The high prevalence of problems attributable to Chagas disease among seropositive
      blood donors underscores the need of an epidemiological follow up of these
      individuals.

PMID- 9567395
TI  - [Chronic pancreatitis. A recent national experience with its surgical
      management].
AB  - BACKGROUND: The prevalence of chronic pancreatitis in Chile is not known and
      there is no local information about the surgical treatment of this disease. AIM:
      To review retrospectively the results of surgical treatment of chronic
      pancreatitis. MATERIAL AND METHODS: The charts of 17 patients (12 male), aged 7
      to 65 years old, with chronic pancreatitis that were operated in three different
      Chilean regions, were reviewed. RESULTS: Seven patients had previous endoscopic
      therapeutic procedures (papillotomy in 4 and stent placing in 3). Seven patients
      had been subjected to previous biliary surgical procedures. Indications for
      surgery were severe pain in 14 patients, the suspicion of a pancreatic carcinoma
      in 4 patients, an infected pseudocyst in one and massive bleeding of multiple
      pseudo-aneurysms in a pseudocyst in one patient. Twelve patients were subjected
      to decompressions and 5 to pancreatic resections. There was no operative
      mortality and one transient pancreatic fistula. After an average follow up of 22
      months, pain improved in 94% of cases, pancreatic cancer was diagnosed in one
      patient and 79% of subjects gained weight. One patient became insulin dependent,
      one increased his insulin requirements and one had transient steatorrhea, since
      she could not afford pancreatic enzyme replacement therapy. CONCLUSIONS: The
      multidisciplinary approach of patients with chronic pancreatitis, with selective
      use of surgery, may greatly improve their quality of life.

PMID- 9567396
TI  - [Multiple hepatosplenic abscesses caused by Yersinia enterocolitica in a patient
      with hemochromatosis].
AB  - Yersinia enterocolitica is a gram-negative bacillus that thrives in conditions
      associated with iron overload. We describe an unusual case of a diabetic patient
      with a previously unrecognized hemochromatosis presenting with Y. enterocolitica
      septicemia. He was admitted because of a 10 day history of abdominal pain, fever
      and jaundice. Blood cultures grew Y. enterocolitica. The abdomen CT scan showed
      multiple liver and splenic abscesses. Antibiotic treatment with ciprofloxacin (2
      months) resulted in a good clinical response. Serum iron studies showed iron
      overload. Liver biopsy revealed moderate fibrosis and early cirrhosis with large
      amounts of hemosiderin granules deposited in hepatocytes and bile duct
      epithelium. This report reviews the literature and highlights that iron overload
      must be ruled out in Yersinia septicemia patients.

PMID- 9567397
TI  - [Mycetomas caused by Microsporum canis. Report of one case].
AB  - We report an eight years old boy presenting with a pyogenic granuloma of the
      scalp, generalized alopecia, descamative plates in the neck, trunk and limbs and
      nail involvement. Cultures for fungus of all these lesions disclosed Microspore
      canis. The patient was treated with oral griseofulvin, miconazole and topical
      tolnaftate. Five years later and after several incomplete treatments, the patient
      returns with a fistulous mass of 15 x 8 cm in the dorsal area whose culture
      revealed Microspore canis. The mass was excised and oral ketoconazole was
      indicated. After three months of follow up, the patient was lost from control.

PMID- 9567398
TI  - [Balo concentric sclerosis. Report of one case].
AB  - We report a 50 years old woman admitted to the hospital due to progressive
      dysphagia and disarthria of there weeks duration. On admission a right
      hemiparesis was noted. CSF examination showed a protein of 9 mg/dl and no cells.
      A brain CAT scan showed rounded bilateral subcortical frontoparietal hypodense
      zones peripheral contrast material enhancement. Pseudobulbar palsies and
      hemiparesis worsened and the patient required nasoenteral feeding. She was
      discharged after four months, with severe disabilities, with the diagnosis of
      Balo concentric, a progressive demyelinating disease.

PMID- 9567399
TI  - [Medical liability in the treatment of intensive care unit patients].
AB  - Critical care medicine was practiced informally during several years, specially
      during war periods. Nowadays it is, however, a fundamental part of health systems
      in which patients attain care facilities of increasing complexity in a cost
      effective manner, according to their needs. The importance of this discipline in
      Chile, during its 30 years of development, has progressively increased and at the
      present time, intensive care units represent up to 30% of the total number of
      beds in some hospitals. Even though these units require great budgets and many
      resources, their place and the role of physicians who work in them has not been
      recognized adequately by the national medical community. The present document
      presents the official position of the Chilean Society of Intensive Medicine on
      the general objectives of this discipline. It indicates the scope of action of
      the specialty and the role of intensive care physicians, their relationship with
      other specialties, their duties and responsibilities with their patients.

PMID- 9567400
TI  - [Nitric oxide in respiratory diseases].
AB  - Recent reports have described a pathogenic role of nitric oxide in several
      respiratory disease. It is specially useful in the adult respiratory distress
      syndrome, where it acts as a selective vasodilator and improves gas exchange,
      decreasing pulmonary shunting. Although it has a proven bronchodilator effect,
      its therapeutic role in diseases such as asthma and chronic limitation of airway
      flow is not well defined. This article review the metabolism, mechanisms of
      action, potential uses and adverse effects of nitric oxide in respiratory
      disease.

PMID- 9567401
TI  - [Eradication of Helicobacter pylori in developing countries].
AB  - A NIH Consensus Conference recommended Helicobacter pylori eradication to all
      ulcer patients, based mainly on information coming from countries with a low
      prevalence of infection in general population. The epidemiological situation is
      different in developing countries, where a pandemic of H. pylori goes unchecked,
      and most people become infected at young age. It is possible that response to
      eradication therapies and reinfection rate were to be included among the
      differences between developed and developing countries, raising doubts about the
      worldwide applicability of NIH recommendations. Limited published evidence and
      our experience suggest that eradication therapies have a lower efficacy and
      reinfection rate is significantly higher in developing compared to developed
      countries. In spite of this, the risk of ulcer recurrence after H. pylori
      eradication is substantially reduced compared to antisecretory therapy. Model
      analysis to evaluate the cost-effectiveness of H. pylori eradication, using
      figures that probably include the clinical and costs situation of developing
      countries, suggests that also from an economic perspective H. pylori eradication
      should be the standard treatment for peptic ulcer disease in developing
      countries. Local studies must determine the best eradication therapy for a
      particular geographical location, and longer follow-up of eradicated patients is
      needed to determine the true reinfection rate.

PMID- 9567403
TI  - [A computerized bibliographic search of articles in the Revista Medica de Chile.
      An article on cat-scratch disease].

PMID- 9567402
TI  - [Characteristics and management of morbidity in seven Chilean cities].
AB  - BACKGROUND: Health population inquiries give information about morbidity as
      perceived by people, the quality of medical care and the costs of diseases. AIM:
      To inform the results on morbidity and medical care surveys performed in the
      Chilean cities of Antofagasta, La Serena, Concepcion, Temuco, Llay Llay, Tiltil y
      Lampa-Batuco. MATERIAL AND METHODS: A random sample of 951 dwellings with 4.192
      people was selected and studied three times, in 1995 and 1996. All health events
      (acute and chronic disease episodes, accidents, health examinations, dental care)
      and the main features of medical care were registered in the interviews which
      covered a 2-week period each time. RESULTS: Health events were registered in
      30.1% people. When extrapolating fortnight findings to a one year period, each
      person had 2.37 annual episodes of acute diseases, 0.94 health examinations and
      0.69 dental attentions. The prevalence of chronic diseases was 13.2%. The
      frequency of health events was higher among women and in elders. Hospital stays
      and deaths were less frequent in higher income levels. Most acute diseases were
      respiratory illnesses, followed by communicable diseases. The most important
      chronic diseases detected were hypertension, diabetes mellitus, bronchial asthma
      and heart diseases. Medical care was provided in 66% of acute and 34% of chronic
      diseases. CONCLUSIONS: When comparing these results with previous surveys, an
      increase in the frequency of acute and chronic diseases is found.

PMID- 9567404
TI  - [Physical activity, health and aging].

PMID- 9567405
TI  - [Plastic surgery or esthetic surgery?].

PMID- 9567406
TI  - [Free flaps in the reconstruction of head and neck. Clinical experience].
AB  - The reconstruction of head and neck defects, due to trauma, tumor resection or
      other, begins with a careful assessment of the patient and the respective defect.
      Ideally, it ends with the successful reconstructive procedure that optimally
      restores form and function to the patient. Free flaps have often been used as a
      last resort reconstructive option in the head and neck because of the need for
      added technical skill, a longer operating time and a perception of poor
      reliability. This study reviews our experience with forty-eight patients
      submitted to microvascular reconstructive procedures. Twelve different kinds of
      free flaps have been involved as the preferred choice for free flap
      reconstruction of a specific defect of the head and neck. The latissimus dorsi
      flap was used for scalp and skull reconstruction, whereas the serratus anterior
      or rectus abdominis free flaps were used for the reconstruction of complex
      defects of the middle third of the face. The radial forearm flap and the free
      jejunal transfer have become the preferred choices for intraoral and pharyngo
      esophageal reconstruction, respectively. Good results were obtained with both
      functional and social rehabilitation. There were three flap losses probably due
      to thrombosis of the microvascular anastomosis. There was no surgical mortality.
      The indications for each free flap are discussed.

PMID- 9567407
TI  - [Total rehabilitation of cleft palate and lip].

PMID- 9567408
TI  - [History of the treatment of fractures of the face].
AB  - Throughout most of recorded human history, facial fractures have received either
      no treatment what so ever or only rudimentary surgical attention. The treatment
      of facial fractures has made more progress over the past two decades than in the
      entire two millenia before that. The authors describe how facial fractures have
      been treated since the New Kingdom in Ancient Egypt until today, with the methods
      of Stable Internal Fixation.

PMID- 9567409
TI  - [Traumatic lesions of the brachial plexus].
AB  - The diagnosis and treatment of brachial plexus lesions have developed remarkably
      in recent decades. The knowledge of anatomy and histology, the physiology of
      lesions, and the definition of ideal conditions for nervous regeneration created
      the basic support, which caused the use of microsurgery to improve the surgical
      results of these lesions. On the other hand, patients used to be seen by
      specialists from different fields, no one saw the need to join efforts in order
      to achieve a multidisciplinary approach. These lesions essentially affect young
      males who belong to a social and professional environment in which motorcycles
      are usually used as their main means of transport. The correct diagnosis of this
      histology is based on a clinical analysis of each case, which requires separate
      evaluations in some instances. Only thus is it possible to establish a
      therapeutic plan in which physiotherapy plays a permanent and vital role.
      Complementary studies always included electromyography, which seems to be a
      useful guide to the progression of the lesions. For operated cases, cervical
      myelography, ultrasonography and magnetic resonance seem to be a useful aid to
      characterise the lesions and define the prognosis. The therapeutic decisions must
      be early and convenient. We found all types of nervous lesions and performed
      various types of surgery with microsurgery techniques, mostly using nerve grafts.
      In the case of infra-ganglion lesions. nerve grafts were used to neurotize
      peripheral nerves from proximal stumps. In case of supra-ganglionic complete
      lesions, we used the accessory spinal nerve, the motor branches of the cervical
      plexus and the intercostal nerves. In relation to peripheral neurolization, we
      tried to establish a certain order, beginning with reinnervation of muscles
      responsible for proximal function.

PMID- 9567410
TI  - [Cutaneous reconstruction at the leg and foot level. Experience in 277 clinical
      cases].
AB  - The authors present their clinical experience of leg and foot reconstruction with
      227 clinical cases. Based on these cases the authors analyse the use of 18
      musculocutaneous, 53 axial, 72 septocutaneous and 84 free flaps, totalling 29
      different kinds of flaps performed. Although no definitive conclusions can be
      drawn about which are the best flaps for foot and leg reconstruction, the
      preferential options are pointed out.

PMID- 9567411
TI  - [Evaluation of the surgical treatment of trapeziometacarpal arthroses].
AB  - The authors describe their experience, from July 1995 to December 1996, in the
      management of patients suffering from trapeziometacarpal degenerative arthrosis.
      Dell's classification is used for disease staging. The results of two different
      techniques are compared: 1) distal tenotomy of supranumerary insertions of
      abductor pollicis longus; and 2) trapeziectomy with tendon interposition
      arthroplasty and ligamentoplasty using the flexor carpi radialis.

PMID- 9567412
TI  - [Postmastectomy breast reconstruction. 10-year experience in the hospital of
      Santarem].
AB  - The authors describe ten years of experience in breast reconstruction in the
      Department of Plastic and Reconstructive Surgery in the District Hospital of
      Santarem--Portugal. Ninety-nine patients were treated with 106 reconstructions,
      most of these were immediate and some were delayed. The authors were interested
      in providing an adequate volume, but also into obtaining an acceptable aesthetic
      result. This contributes considerably to the psychological recovery of the
      patients.

PMID- 9567413
TI  - [Avulsion of the skin of the penis and scrotum].
AB  - The authors present a case report of traumatic avulsion of the skin of the penis
      and scrotum. Surgical treatment was performed in one surgical stage a few hours
      after the accident. The skin repair of the penis was carried out with a skin
      graft, while scrotum reconstruction was performed with fasciocutaneous flaps of
      the inner face of the thighs, with supero-medial pedicle, achieving a good
      result. The authors justify their choice of procedure, also mentioning the other
      methods most employed.

PMID- 9567414
TI  - [Inhalation lesions in the burn patient].
AB  - Inhalation injuries are currently the factor most responsible for mortality in
      thermally injured patients. Inhalation injuries may occur independently, but
      generally occur together with skin burn. Smoke inhalation affects all levels of
      the respiratory system and the extent of the inhalation injury depends on the
      duration, exposure, amount and toxicity of the fume temperature, concentration
      and solubility of toxic gases, the occurrence of the accident in a closed space
      and pre-existing diseases. Smoke inhalation also induces changes in the systemic
      organs with the need for more fluid for resuscitation. Systemic vasoconstriction,
      with an elevation in systemic vascular resistance, a fall in myocardial
      contractility and a great increase in lymphatic flow in soft tissue are the most
      important changes in systemic organs. On admission of a burn patient there is a
      high suspicion of inhalation injury when there are signs and symptoms such as
      hoarseness, strides, dyspnea, carbonaceous sputum, anxiety or disorientation,
      with or without face burns. The patient with these findings has partial airway
      obstruction and there is substantial risk complete airway obstruction occurring
      of secondary to the edema. Patients with suspected inhalation injury should be
      intubated so as to maintain airway patency and avoid a total obstruction. This
      group of patients frequently develop respiratory failure with the need for
      mechanical ventilatory support. Nosocomial infections, sepsis and multiple organ
      system failure may occur. Late complications of inhalation injury are tracheitis,
      tracheal stenosis or tracheomalacia and chronic airway disease, which is
      relatively rare. Early diagnosis of inhalation injury and treatment in a Burn
      Unit by a group of highly motivated clinicians and a good team of nurses is
      essential in order to decrease the morbidity and mortality related to inhalation
      injury.

PMID- 9567415
TI  - [Feeding in burn patients].

PMID- 9567416
TI  - [Serial and multiple tissue expansion in burn sequela].
AB  - The authors present the case of a 16 year old female with 3rd degree burn
      sequelae. They describe the surgical steps during the three years of treatment
      with serial and multiple tissue expansion. From the 9 tissue expanders used with
      reference capacities of 3350cc, 10350 were achieved. The conclusions point out
      the utility of this technique, using re-expansion and supraexpansion as one,
      should be associated with careful surgical planning and constant rapport with the
      patient.

PMID- 9567417
TI  - [Marjolin ulcer].
AB  - Marjolin Ulcer is a squamous cell carcinoma developed in a burn scar. The term
      was applied to all malignancies developed in scars or chronic draining sinuses,
      and its connotation with burn scars has been forgotten. It is an uncommon tumour
      in the developed world. The scars with iterative ulcerations are the ones that
      could be the origin of a carcinoma. As regards pathogenesis, it is attractive to
      speculate about the relation between wound healing and cutaneous malignancy since
      these processes share common tissue factors. The author presents his experience
      in the treatment of these tumours. Regarding prognosis and treatment, it is the
      author's opinion that carcinoma from scars are curable by adequate local
      excision, contrally to carcinoma of chronic sinuses, namely osteomyelitis,
      because cancer cells tend to follow the fistulous tract and multiply inside the
      bone cavity, generally only amputation is effective. Finally the author stresses
      that with good treatment vicious scars or draining sinuses could be prevented,
      therefore Marjolin Ulcer is an entity that disappears with good health care.

PMID- 9567418
TI  - [Topography of facial aging].
AB  - The Author studies the ageing process of human tissues, pointing out the main
      histologic features and functional decrements of the human skin, and some
      exogenous factors. The topographical study of the aging face is presented in
      accordance with the aesthetic division of the face into three thirds, plus the
      anterior cervical region. In each one of these sectors, from a clinical point of
      view, the Author describes the stigma and changes produced by ageing on the skin,
      fatty tissue, muscles and bones.

PMID- 9567419
TI  - [Open rhinoplasty. 5-years experience].
AB  - The principle advantages of open rhinoplasty concern diagnosis as well as
      technical facilities. The transcolumelar approach, initially described by Rheti
      in 1934 for surgical corrections of the cleft lip nose, was adopted by us since
      1992 in 48 patients. We have systematically made a "staggered incision" at the
      collumella's narrowest point, that allows a great view of nasal structures. The
      results were considered good, even in difficult rhinoplasties. The scars were
      inconspicous, without cicatricial hypertrophies or deformities.

PMID- 9567420
TI  - [Multidrug combination therapy in HIV infection treatment: "monotherapy has died,
      long live multidrug therapy!"].

PMID- 9567421
TI  - [Efficacy and safety of zidovudine in monotherapy in patients with HIV
      infection].
AB  - BACKGROUND: To study the efficacy and the tolerance of the zidovudine (ZDV) in
      monotherapy for the treatment of a cohort of patients with HIV infection, most of
      them injection-drug users (IDU). METHODS: Retrospective study of a historic
      cohort of 350 patients, from January 1988 to December 1994. The clinic
      progression, the immunologic deterioriation and the survival after the ZDV
      administration were evaluated, like the toxicity of the drug. RESULTS: The
      estimated progression time to AIDS for the 25% of the cohort was 29 months for
      the initially asymptomatic patients and 22 months for the subjects who showed
      symptoms. After 26 months half of the patients showed CD4 cell counts less to 50%
      of the basals. The cumulative survival probability after a year was 99%, 97% and
      85% for the groups A, B y C of the CDC classification, and 94%, 87% and 58% after
      two years for these groups. The predictive factors associated with the survival
      were the clinic and immunologic status, ESR, LDH, and beta 2-microglobulin levels
      at the beginning of the treatment. The 35% of the patients suffered adverse
      events, mainly hematologic effects, although they only forced to suspend the
      treatment in the 5% of the cases. The only predictive factor associated with the
      toxicity was a neutrophile count less than 1.500 cells/mm3 previous to the
      treatment (p < 0.001). CONCLUSION: The ZDV use in monotherapy in a cohort of
      patients majority IDU shows the same efficacy and safety as the treatment in
      other patients with HIV infection.

PMID- 9567422
TI  - [Efficacy of combining zidovudine plus didanosine in patients with and without
      previous exposure to zidovudine].
AB  - BACKGROUND: The virologic and immunologic efficacy of the combination of
      zidovudine (ZDV) and didanosine (DDI) was examined in 27 HIV-infected patients.
      METHODS: 27 HIV-infected patients, 15 of whom were naive for antiretroviral
      drugs. The remaining 12 subjects had been exposed to ZDV for at least 16 weeks.
      Mean plasma viral load was of 4.7 logs and 4.5 logs, respectively. All patients
      had less than 350 x 10(6)/l CD4+ T lymphocytes at baseline. RESULT: Significant
      reductions in viremia (> 0.5 logs) were seen at the first and third months,
      respectively, in 71.4% and 64.3% of naive patients. In contrast, it occurred only
      in 10% and 0%, respectively, of pre-treated patients. Moreover, the CD4 count
      only increased significantly (> 15%) in naive individuals. Changes in serum p24
      antigenemia were not significant in both groups neither at the first nor at the
      third months of began therapy. CONCLUSION: The antiviral efficacy of the ZDV plus
      DDI combination is limited and transient in patients with advanced HIV disease,
      and disappears in subjects already exposed to ZDV.

PMID- 9567423
TI  - [Combined antiretroviral therapy for prevention of vertical HIV-1 transmission].
AB  - A 25-year old woman with rapid HIV disease progression had been receiving
      zidovudine (ZDV) for two years, when she became pregnant. She had a high viral
      load and carried out zidovudine-resistant viral strains. For these reasons, and
      with the main objective to maximally reduce viremia, the association of DDI to
      ZDV was introduced a few weeks before delivery. The virological follow-up for one
      year has confirmed the lack of HIV infection in the child. Combined
      antiretroviral therapy during the last weeks of pregnancy might be considered for
      the prevention of vertical transmission of HIV in cases of high risk of newborn
      infection, without adding relevant toxicity.

PMID- 9567424
TI  - [Bronchiolitis obliterans organizing pneumonia. Experience in a second level
      hospital].
AB  - Bronchiolitis obliterans organizing pneumonia is a disease characterized by the
      presence of granulation tissue within small airways and areas of organizing
      pneumonia. Over the last three years two patients were studied. Its clinical
      spectrum, radiological presentations and spirometric findings are discussed.
      Response to treatment with steroids was favorable.

PMID- 9567425
TI  - [Cytomegalovirus acalculous cholecystitis in an AIDS patient].
AB  - We report a case of acalculous cholecystitis in an AIDS patient, that appeared
      with insidious onset, abdominal right upper quadrant pain and fever.
      Cholecystectomy was performed and CMV inclusions were observed in tissue
      sections. CMV acalculous cholecystitis is an uncommon condition associated to the
      acquired immunodeficiency syndrome. It should be considered, especially when
      abdominal pain and fever are present in marked immunosuppressed AIDS patients.
      Unfortunately, a limited experience in treatment, either medical or surgical, was
      reported. In our case, the response to surgical procedure was successful,
      disappearing the abdominal pain and the fever. The patient refused both
      ganciclovir and foscarnet therapy.

PMID- 9567426
TI  - [Past, present and future of zidovudine, the first antiretroviral drug].
AB  - The zidovudine (ZDV) was the first drug approved to treat the VIH infection. The
      ZDV prescriptions have been changing throughout the years. Actually it's known
      that its efficacy is limited over time, and same substances have been discovered
      which inhibtes more strongly the VIH replication. However the ZDV appears in
      majority the combined therapy regimens as a first line drug. Even in same special
      situations there is no existence of another antiretroviral drugs which have
      showed utility. In this essay it s revised the mainly studies which have provided
      new knowledge about the ZDV treatment and it s also considered the possibilities
      of this drug in the more new therapies against the VIH.

PMID- 9567427
TI  - [A new case of ciguatera fish poisoning and favorable evolution with
      corticotherapy].

PMID- 9567428
TI  - [Alcohol induced pseudo-Cushing's syndrome versus cushingoid phenotype].

PMID- 9567429
TI  - [Foscarnet and tetany, is prevention possible?].

PMID- 9567430
TI  - [Calcium antagonists, not long acting].

PMID- 9567431
TI  - [Rhabdomyolysis after ingestion of toxins].

PMID- 9567432
TI  - [Cardiovascular risk factors in Alcala de Henares. A lost opportunity?].

PMID- 9567433
TI  - [Gemfibrozil induced impotence].

PMID- 9567434
TI  - [Sepsis from Gemella morbillorum].

PMID- 9567435
TI  - How data influence third party payers.

PMID- 9567436
TI  - Kindred spirits: finding then in ASHA's special interest divisions.

PMID- 9567437
TI  - Telehealth. Part II. A total system approach.
AB  - Digitization and telecommunications technology makes possible greater access to
      health care for remote and underserved populations. But although many telehealth
      programs were implemented over the last 25 years, few have survived withdrawal of
      external funding. This, in spite of data indicating few hardware problems and
      that in general patients are satisfied with their experiences of telehealth.
      What's the problem? Why are telehealth programs marginally successful at best?

PMID- 9567438
TI  - It's about time ... saving now for later.

PMID- 9567439
TI  - Retirement planning.

PMID- 9567440
TI  - The need for phonemic awareness.

PMID- 9567441
TI  - Activities to encourage speech and language development.

PMID- 9567442
TI  - No conflict between religion, healing.

PMID- 9567443
TI  - Managing audiological aspects of care.

PMID- 9567444
TI  - Resource for kids with apraxia.

PMID- 9567446
TI  - Hearing loss: terminology and classification. Joint Committee of the American
      Speech-Language-Hearing Association and the Council on Education of the Deaf.
AB  - The following position statement and technical report were developed by the Joint
      Committee of the American Speech-Language-Hearing Association (ASHA) and the
      Council on Education of the Deaf (CED) and approved as Association policy by the
      ASHA Legislative Council in November 1997 (LC 6-97). CED member organizations are
      reviewing the document for approval in 1998. Joint Committee members responsible
      for the development of this document include (from ASHA) Joan Marttila, chair
      1996-97; Linda Seestedt-Stanford, chair 1994-95; Evelyn Cherow, ex official;
      Donald Goldberg; Dawna Lewis; Leslie Ann McMillian; Jane Seaton; Alicia Stewart;
      and Larry Higdon, vice president for professional practices in audiology and
      monitoring vice president; and (from CED) Kathee Christensen; Steve Nover;
      Marilyn Sass-Lehrer; and Patrick Stone. This document supersedes ASHA policy:
      Definitions of Communication Disorders and Variations: Hearing Disorders section.

PMID- 9567445
TI  - Position statement and guidelines on support personnel in audiology. American
      Speech-Language Hearing Association.
AB  - This policy document of the American Speech-Language-Hearing Association (ASHA)
      reflects the Association's position that the Certificate of Clinical Competence
      Audiology (CCC-A) is a nationally recognized quality indicator and education
      standard for the profession. The following statement includes the CCC-A as the
      appropriate credential for audiologists supervising support personnel. The
      consensus panel document's exclusion of the CCC-A conflicts with ASHA's policy.
      Member organizations that composed the consensus panel on support personnel in
      audiology included: Academy of Dispensing Audiologists (ADA), American Academy of
      Audiology (AAA), ASHA, Educational Audiology Association (EAA), Military
      Audiology Association (MAA), and the National Hearing Conservation Association
      (NHCA). Representatives to the panel included Donald Bender (AAA) and Evelyn
      Cherow (ASHA), co-chairs; James McDonald and Meredy Hase (ADA); Albert deChiccis
      and Cheryl deConde Johnson (AAA); Chris Halpin and Deborah Price (ASHA); Peggy
      Benson (EAA); James Jerome (MAA); and Lloyd Bowling and Richard Danielson (NHCA).
      ASHA's Legislative Council and Executive Board elected not to adopt the consensus
      panel document because it excluded the CCC-A. In all others aspects, the
      documents remain similar. This position statement and guidelines supersede the
      audiology sections of the Guidelines for the Employment and Utilization of
      Supportive Personnel (LC 32-80).

PMID- 9567448
TI  - Students and professionals who speak English with accents and nonstandard
      dialects: issues and recommendations. ASHA Joint Subcommittee of the Executive
      Board on English Language Proficiency.

PMID- 9567447
TI  - Provision of English-as-a-second-language instruction by speech-language
      pathologists in school settings. ASHA Multicultural Issues Board.

PMID- 9567449
TI  - Maximizing the provision of appropriate technology services and devices for
      students in schools--executive summary. Ad Hoc Committee on Maximizing the
      Provision of Appropriate Technology Services and Devices for Students in Schools.

PMID- 9567450
TI  - Cytokeratin intermediate filaments in oral and odontogenic epithelia.
AB  - With the development of monoclonal antibodies, the intermediate filaments of the
      cytoskeleton have attracted a great deal of interest in the last twenty years.
      Because they are highly antigenic, they could be easily identified using
      immunohistochemical methods and their specificity for one type of cell offered
      possibilities in the field of diagnostic pathology. The intermediate filaments
      most specific for epithelial cells are the cytokeratins (CK). After CK were
      classified, and certain "rules" regarding CK defined, research proceeded a pace
      to investigate epithelia in a vast array of anatomical and pathological
      situations. However, much of the immunohistochemical data that was generated
      during the 1980's was difficult to digest and some difficult to interpret.
      Reasons for this include identification of CK by molecular weight rather than CK
      number, or confusion as to which CK were being labelled by a particular antibody
      clone known to detect more than one CK. The aim of this article is therefore to
      present a digest of current knowledge of the CK present within the epithelium of
      the oral cavity (including the odontogenic epithelium) and its glandular
      component, and to highlight the significance of the CK phenotype in our
      understanding of pathological change.

PMID- 9567451
TI  - Oral hairy leukoplakia with ultrastructural evidence of Merkel-like cells in
      human tongue epithelium.
AB  - The purpose of this investigation was to examine cells in the stratum basale and
      subjacent lamina propria of oral hairy leukoplakia (OHL) specimens for previously
      unreported morphological changes. Tongue biopsy specimens were obtained from ten
      HIV-positive and five healthy male patients and examined by light (LM) and
      transmission electron microscopy (TEM). Observations made during the
      investigation revealed the following: (1) LM comparisons of control and OHL
      specimens indicated that clear cells in the stratum basale ranged from 3 to 7 per
      100 basal epithelial cells in healthy tongue mucosa vs. 6 to 15 in OHL. (2)
      Merkel-like cells were noted in the stratum basale of control biopsies from the
      dorsal-lateral tongue surface. However, the frequency of observation was so rare
      as to imply that their presence was an exception rather than the norm. (3) In
      contrast, Merkel-like cells in OHL specimens were commonly encountered,
      indicating a possible unique relationship to the pathology. (4) Merkel-like cells
      associated with OHL lesions were morphologically similar, in all respects, to
      that of control specimens except for the presence of large, membrane bound, dense
      granules that ranged in size from 150-300 nm. (5) All biopsies of OHL exhibited
      evidence of Epstein Barr virus in the stratum corneum and superficial layers of
      the stratum spinosum. (6) A mild inflammatory infiltrate associated with OHL
      specimens revealed cytopathic changes in fibroblasts that appeared related to the
      presence of lymphoid cell types; indicating a possible cytolytic lymphocyte
      mediated degradation of antigen altered host cells.

PMID- 9567452
TI  - Glass ionomer cement, an intelligent material.
AB  - The main task of a dental filling material is to permanently seal the dentinal
      wound and to restore the anatomy. In particular with respect to the former
      requirement, glass-ionomer cements exhibit, thanks to it's ingenious composition,
      unique properties, which allows it to react on external information in such a way
      that the cement automatically and adequately fulfills it's function as a proper
      restorative material. Because of it's setting mechanism, glass-ionomer cement
      restorations have a better perspective to seal the tissue than amalgam or resin
      composites do. As resistance to wear of glass ionomers is inferior to resin
      composites it proves to be a better dentin replacement, than a substitute for
      tooth enamel. Restorations made in a combination of glass-ionomer cement and
      resin composite, the so called sandwich restorations, have shown to function
      excellently, both at the tooth interface as well as the outer surface. As any
      leakage still cannot be excluded, the fluoride release at the margins of the
      restoration forms a wellcome contribution to the prevention of secondary caries.
      Once more, glass-ionomer cement shows to be intelligent by automatically
      activating an advantageous process when the environment requires it.

PMID- 9567453
TI  - Follow-up treatment after surgery of internal derangement of temporomandibular
      joint--a survey of 20 patients.
AB  - The effect of surgical treatment of internal derangement of temporomandibular
      joint (TMJ) combined with regular follow-ups was evaluated in 20 patients (16
      women, 4 men, mean age 38 years, range 17-58 years). The function of the
      masticatory system was examined before surgery and at 3 months, 6 months and 1
      year afterwards. The follow-up treatment immediately after operation included the
      use of analgesics for two to four weeks and mobilization exercises of the lower
      jaw, beginning the day after the operation. Twelve patients had complete or
      virtually complete dentition and six patients had prosthesis. The occlusal
      adjustment and occlusion of the prosthesis was corrected or new prosthesis was
      constructed approximately six months after surgery. Degree of temporomandibular
      disorders (TMD) was assessed using the clinical dysfunction index of Helkimo. A
      statistically significant decrease (p < 0.001) was seen in the scores of the
      dysfunction index in all recordings after surgery compared to preoperative
      values. All the ranges of the mandibular movements increased statistically
      significantly. It seems that regular follow-ups and adequate oral rehabilitation
      after surgery of internal derangement of TMJ have a great influence on the
      outcome of the surgical treatment of TMJ.

PMID- 9567454
TI  - Role of endogenous proteases and their inhibitors in periodontal diseases.

PMID- 9567455
TI  - [The Romanian Society of Surgery--a century of activity].

PMID- 9567456
TI  - [Immediate and early reinterventions in the surgery of colorectal cancer].
AB  - Out of 584 cases submitted to colorectal surgery 461 (78.92%) were performed for
      cancer. Thirty-three patients (7.16%) necessitated immediate (1) or precocious
      reinterventions for bleeding, fistulae, peritoneal infections, bowel occlusion,
      necrosis or stenosis of the iliac anus. We are out the technical procedures
      chosen for each class of complications asking for reintervention. We registered 4
      deaths, in aged patients with hard associated morbidity, with emergency
      reinterventions. We appreciate that a correct preoperative preparation reduces
      the rate of reintervention and an early reintervention reduces the post-operative
      mortality.

PMID- 9567457
TI  - [Sandostatin treatment in postoperative external digestive fistulae].
AB  - The aim of the conservative treatment of postoperative external digestive
      fistulae is to obtain a reduction of the output, thus favoring spontaneous
      closure and shortening outcome. A retrospective comparative study has been
      performed on two groups of patients with postoperative anastomotic
      gastrointestinal and pancreatic fistulae. Group A included 18 cases (14
      anastomotic, 4 pancreatic fistulae) receiving conventional treatment only. Group
      B included 25 cases (18 anastomotic and 7 pancreatic fistulae) in which
      Sandostatin was associated to conventional therapy, using daily doses ranging
      from 0.1 mg to 0.3 mg, administered after variable intervals after fistulas'
      occurrence. Duration of treatment ranged from 1 to 25 days. In group A, 27.77% of
      the cases were cured in comparison with group B in which the healing rate
      increased to 56%. Global hospital mortality rate was 25.58% (11 cases). In group
      A this was 44.44% (8 cases) in comparison with group B with 12% (3 cases) only.
      As a conclusion of our study, the use of Sandostatin is remarkable effective in
      the treatment of external digestive postoperative fistulae. Thus a doubling of
      healing rate and a reduction by 73% of mortality rate was achieved.

PMID- 9567458
TI  - [Pancreatic fistula after cephalic duodenopancreatectomy. Its incidence,
      significance and therapeutic characteristics].
AB  - In this paper the authors present a study of pancreatic fistula after cephalic
      duodenopancreatectomy concerning the incidence, importance and the therapeutic
      features in a number of 37 patients operated between 1.Jan.1990-1.Jan. 1997 at
      the 1st Department of Surgery of Clinical County Hospital of Targu-Mures. A
      number of 8 patients (22%) had pancreatic fistula; a half of them were treated by
      surgical reintervention, and the second half by conservative procedures.

PMID- 9567459
TI  - [Clinical and therapeutic considerations in pseudomyxoma peritonei].
AB  - Pseudomyxoma peritonei (PMP) is an uncommon clinical entity, lacking a precisely
      defined etiopathogenesis. Its clinical features are not specific and diagnosis is
      difficult. We analysed 10 patients, all of them women, whom we had treated
      surgically in combination with intraperitoneal chemotherapy. Postoperative
      complications had been minimal and no death had occurred. 5 patients were
      followed up in time, 4 of them presenting a favourable evolution (2 required
      reintervention), and 1 patient decreased. We analysed up-to-date therapeutic
      approaches and the benefit of their combinations in order to identify the optimal
      therapeutic strategy. We consider that the combinations surgery + intraperitoneal
      chemotherapy or surgery + intracavitary radiotherapy are the most effective up to
      date.

PMID- 9567460
TI  - [A new surgical technic in the treatment of uncomplicated hepatic hydatid cyst].
AB  - The authors are presenting a new surgical technique in the therapeutical arsenal
      of the II-nd Surgery Clinic, County General Hospital, Constanta starting with
      this year, 1997, for the surgical treatment of the uncomplicated hydatid cyst of
      the liver. Without any present evaluation of the results, the article describes
      the technique in accordance to the world scientific literature. This procedure
      consists of a minimum cystotomy with the extraction of the proligerous membrane
      and tight cystorafta after introducing 9/1000 sodium chloride in relative
      tension. The minimum approaching incision, the short time of the operation, the
      elimination of the "annoying" cavitary and intra-abdominally drin tubes, the fast
      social reintegration include this technique in the group of the minimum invasive
      surgical procedures and recommend its application in the uncomplicated hydatid
      cyst of the liver.

PMID- 9567462
TI  - [A rare cause of postoperative digestive hemorrhage].
AB  - Despite all the diagnosis's technical progress achieved in the past years, there
      are possible haemorrhagic complications after abdominal surgery, creating
      problems of diagnosis and treatment. The author presents a rare case of
      postoperative gastrointestinal bleeding due to an ulcer of the jejunal mucosa,
      located quite close to a hepaticojejunostomy. The mucosal ulcer, with consequent
      severe, massive bleeding was caused by the migration of a thread from the
      hepaticojejunostomy, proved by histopathological examination.

PMID- 9567461
TI  - [Anterior resection of the rectum via laparoscopy].
AB  - Of the newer laparoscopic procedures for colorectal cancers the abdominoperineal
      resection of the rectum was previously communicated in this journal. The
      laparoscopic anterior resection is a more technically demanding operation. We
      report the case of 63 years old women with a rectal cancer at 9 cm from the anus.
      The procedure was realised under general anaesthesia, with a urinary catheter in
      place. An blunt obturator was introduced into the uterine cavity and used to
      manipulate the uterus during the procedure. After establishing of the
      pneumoperitoneum, a 30 degrees telescope was introduced through the umbilical
      port (10 mm). The 30 degrees telescope allows visualization of the splenic
      flexure and rectal side wall. The main steps of the procedure were the
      exploration of the abdominal cavity, mobilization of the descendent colon and
      sigmoid, exposure of the left ureter, division of the left sided peritoneal leaf
      and division of the inferior mesenteric vessels. The anterior dissection of the
      rectum was facilitated by manipulation of the uterus. The rectum was then
      mobilized with the "abdominalization of the tumor". A 5 cm left paramedian
      vertical incision was performed; through this incision a stapler was introduced
      and the rectum was transected 5 cm under the tumor. The rectum with the tumor,
      the sigmoid and mesosigmoid were exteriorized through the incision; the sigmoid
      was divided with a linear stapler cutter 20 cm above the tumor and the specimen
      was removed extracorporeally. The anvil of a circular stapler was secured in the
      left colon and returned in the abdominal cavity. The body of the stapler was
      inserted into the rectal stump through the anus and connected intracorporeally to
      the anvil. The postoperative evolution was simple; flatus and feces were passed
      at 48 hours. The patient was discharged to home after 6 days, 13 months after
      operation she has no morbidity.

PMID- 9567463
TI  - [Statistical structure of the interaction between the main EEG components in
      children of school age].

PMID- 9567464
TI  - [Neurophysiologic mechanisms of delay in psychic development in children.
      Structural analysis of EEG].

PMID- 9567465
TI  - [Dynamics of the rhythmic components in the alpha range of the encephalogram in 7
      8-year-old children during relaxation].

PMID- 9567466
TI  - [Topogram analysis of the spatial-temporal organization of potentials in the
      human cerebral cortex during set formation].

PMID- 9567467
TI  - [Dynamics of EEG coherence in right- and left-handed people when falling asleep.
      II. Analysis of interhemispheric relations].

PMID- 9567468
TI  - [Perception of impulse signals and human evaluation of the direction of motion of
      a sound source in the context of medium intensity noise].

PMID- 9567469
TI  - [Physiological effects of voluntary breath holding in children and adolescents].

PMID- 9567470
TI  - [Reference systems and interpretation of proprioceptive signals].

PMID- 9567471
TI  - [Characteristics of rheologic and acoustic properties of the skin covering of the
      human leg during its stretching].

PMID- 9567473
TI  - [Lymphocyte regulation of cellular growth in somatic tissues and a new immune
      theory of aging].

PMID- 9567472
TI  - [Theoretical substantiation of experimental research on graft survival in various
      phenotypes of xenobiotic metabolism in the donor and the recipient].

PMID- 9567474
TI  - [Evaluation of the renal barrier in Antarctic explorers according to the content
      of apolipoproteins A-I and B in urine in wintering dynamics].

PMID- 9567475
TI  - [Change in pulmonary gas exchange when breathing cold air in non-native
      inhabitants on the Russian North].

PMID- 9567476
TI  - [Age-related dynamics of various physiological functions in inhabitants of the
      Russian North].

PMID- 9567477
TI  - [Effect of ecological factors in an industrial city on the health of students].

PMID- 9567478
TI  - [Effect of ionizing radiation on cellular immunity].

PMID- 9567479
TI  - [Dependence of the secretion of hormones of the fetoplacental complex on the time
      of year].

PMID- 9567481
TI  - [Stress-induced disorders of immune function and their psychocorrection].

PMID- 9567480
TI  - [Effect of phenibut, obsidan and their combination on the human functional state
      in hyperthermia].

PMID- 9567482
TI  - [Lateralization of tactile perception in right- and left-handed people].

PMID- 9567483
TI  - [Characterization of the types of hemispheric response and anxiety level in right
      handed and left-handed individuals in various regions of Russia and Latvia].

PMID- 9567484
TI  - [Comparative evaluation of selective visual attention in healthy subjects and in
      schizophrenic patients].

PMID- 9567485
TI  - [Physical working capacity and the status of central hemodynamics in women with
      alimentary obesity in the process of fasting-diet therapy].

PMID- 9567487
TI  - [Digestive neoplasms of the diffuse neuroendocrine system: physiopathologic and
      clinical aspects].

PMID- 9567489
TI  - [Rupture of the diaphragm caused by closed thoraco-abdominal trauma. Case
      contribution and anatomo-clinical considerations].
AB  - Diaphragmatic rupture is a potentially severe complication of blunt trauma which
      can easily be overlooked during initial emergency department evaluation. Delayed
      diagnosis is due to severe concurrent injuries and lack of specific clinical
      features and instrumental procedures. Clinical features of diaphragmatic
      herniation, in the early presentation, include respiratory symptoms, while
      abdominal symptoms and signs are late. Plain chest radiography repeated, if
      negative, is the main help in the diagnosis: especially in patients managed with
      intermittent positive-pressure ventilation. Experience in five cases of
      diaphragmatic hernia is reported.

PMID- 9567488
TI  - [Is it possible to consider intranuclear DNA imaging analysis as a new parameter
      in the staging of colorectal cancer?].
AB  - Intranuclear DNA imaging may be considered as a marker of the biological
      behaviour of neoplasias. However, some questions fundamentally related to the
      interpretation of cytometric data, to the correlation with other
      histomorphological parameters and to tissue sampling concerning staging and
      prognostic evaluation of colon cancer patients are still unsolved. A way to solve
      this problem may be to perform multiple full thickness samplings.

PMID- 9567490
TI  - [Transpyloric prolapse of a gastric carcinoma arising from a pedunculated
      hyperplastic polyp].
AB  - A case of gastric carcinoma developed on a large pedunculated hyperplastic polyp
      prolapsed into duodenum is reported. The cases of transpyloric prolapsed primary
      pedunculated gastric carcinoma are rare, only 34 cases have been described in
      Japan during the past 35 years, including the sessile forms. These gastric polyps
      should be considered in the differential diagnosis of intraluminar filling
      defects of the duodenal bulb. Endoscopy and biopsy are essential for a correct
      diagnostic evaluation. Large hyperplastic polyps, especially if prolapsed,
      require a surgical excision.

PMID- 9567491
TI  - [Appendiceal "mucocele": apropos of 2 cases].
AB  - Two patients affected by appendiceal mucocele underwent emergency operation in
      our Department. Clinical findings and surgical management of the disease are
      discussed as well as controversy regarding the pathologic classification of the
      disease. The term "mucocele" is not referred to an exact histopathologic lesion:
      it describes the gross enlargement of the appendix, due to the accumulation of
      mucus in the dilated lumen. Currently such lesions are classified as
      nonneoplastic or as retention appendiceal cysts or as mucous-secreting tumours;
      the benign forms are cured by appendectomy, the malignant ones often require
      right colectomy for technical reasons. Pseudomyxoma peritonei significantly
      decreases survival of patients suffering from mucinous cystadenocarcinoma, but it
      does not affect survival in case of mucinous cystadenoma.

PMID- 9567493
TI  - [Neurinoma of the vagus nerve. Description of 2 cases and review of the
      literature].
AB  - The Authors report two rare cases of schwannoma of the cervical and thoracic
      portion of the vagus nerve. Schwannomas of the vagus nerve are particularly
      uncommon; patients suffering from these neurogenic tumors typically exhibit a
      paucity of symptoms and in the majority of cases they present with an
      asymptomatic mass noted on incidental chest X-ray. Chest pain and cough may occur
      with tumors arising next to and compressing the trachea or major bronchi. In the
      cases observed, schwannomas appeared like a mass whose size had increased during
      the last months without producing any clinical symptom. Clinical features of the
      mass, laboratory tests, ultrasound, CT scanning, magnetic resonance imaging were
      useful only to define its extension and relationships with the adjacent
      structures. Needle aspiration of these lesions is not indicated because of the
      paucity of the material obtained for the exact diagnosis. Surgery, with
      preservation of the vagus nerve when possible, is the treatment of choice also
      for a correct diagnosis of nature and to prevent further growth and compression
      on adjacent structures. When the individual fibers of the vagus nerve are
      displayed over the surface of the tumor within a discrete capsule nerve
      preservation is possible. On the contrary, when it is technically difficult to
      preserve the nerve trunk microsurgical procedures allow to reanastomose the cut
      ends. Injury of homolateral recurrent nerve often is the complication of a
      radical removal. Recurrence of benign lesions is not usual; malignant tumors
      carry a poor prognosis with patients rarely surviving beyond 1 year.

PMID- 9567492
TI  - [Post-thymectomy extrathymic tumors].
AB  - The Authors report the case of a 78 year old woman affected with two synchronous
      primary cancers (epidermoid bronchial and rectal adenocarcinoma); 16 years
      previously, after the discovery of a thymoma, she underwent thymectomy. Thus, the
      discussion issue is if post-thymectomy extra-thymic malignancies are to be
      considered just a simple coincidence or a true syndrome.

PMID- 9567495
TI  - [Clinical study of residual function and recurrence in patients undergoing
      partial thyroidectomy for euthyroid nodular goiter].
AB  - The different surgical options for the treatment of non toxic nodular goiter led
      the Authors to study the residual thyroid function following conservative surgery
      (subtotal thyroidectomy, lobectomy and enucleation). Follow-up showed an overall
      recurrence rate of 49%, with a higher rate after lobectomy and enucleation than
      after subtotal thyroidectomy. On the other hand, subclinical hypothyroidism was
      higher in patients who underwent subtotal thyroidectomy. No significative
      correlation was found between high plasmatic levels of TSH and recurrences.

PMID- 9567494
TI  - [Diaphragmatic eventration in the adult: repair with Gore-Tex surgical mesh].
AB  - The Authors report the case of a fifty-nine-year-old patient, affected by
      complete eventration of the left diaphragm and cranial stomach dislocation with
      axial volvulus, associated with an upward movement of part of the left colon and
      some jejunal loops. The subclinical condition had been occasionally discovered
      during a routine chest X-ray at the age of eighteen and the patient remained
      without symptoms up to five years ago, when he began to show significant
      digestive and cardiorespiratory symptoms. The patient has been successfully
      treated via thoracotomy with phrenic alloplastic using Gore-Tex patch and has
      obtained an immediate remission of the symptoms. Left diaphragmatic eventration
      of the adult is a rare pathology, either congenital or acquired, with few and
      definite surgical indications such as severe digestive and cardiorespiratory
      symptoms. Different surgical techniques including the use of patches are herein
      illustrated.

PMID- 9567496
TI  - [Primary gastric lymphomas: analysis and considerations on 7 cases].
AB  - The Authors report on 7 cases of primary gastric lymphoma. Some considerations
      about the diagnosis and the surgical treatment of these tumors are illustrated.

PMID- 9567497
TI  - [Hydatid cysts of the right lobe of the liver treated with total pericystectomy
      using a transparenchymal approach].
AB  - The Authors report on 2 cases of hydatid cyst of the right hepatic lobe. A
      transparenchymal approach with total pericystectomy was the treatment of choice.

PMID- 9567498
TI  - [The rational use of prosthesis in laparocele].
AB  - The Authors report their cases of incisional hernias observed from 1990 to 1995
      involving 142 patients treated either in emergency or under normal conditions. A
      guideline in the choice of prosthetic materials of current use, considering the
      relative chemo-physical characteristics, the biocompatibility and the costs is
      outlined. Although not entering into the merit of the surgical technique some
      general criteria that should guide the surgeon facing the incisional hernial
      pathology are ruled out.

PMID- 9567499
TI  - [Advantages of reabsorbable intradermal sutures in general surgery. Experience on
      201 sutures].
AB  - Surgical wound suture is often considered of minor importance compared to the
      whole surgical operation. The aesthetical result of a wound suture is still
      hardly considered in general surgical practice compared to other "traditional"
      wound sutures. The Authors carried a prospective study an 201 intradermal
      absorbable sutures in clean general surgery. The results clearly show that with a
      limited increase of the mean operation time of 90 seconds, for a 10 cm suture,
      there are such positive clinical, and aesthetical results that it is advisable to
      use routinely this type of suture in elective clean surgery.

PMID- 9567501
TI  - Gastroenteritis due to Vibrio cholerae El-Tor Ogawa in Dhule.
AB  - For V. Cholerae isolation, stool sample is better than rectal swab. Direct
      oxidase test on stool is easy and reliable. V. cholerae El-Tor Ogawa is
      predominant type in Dhule area. New phage type T27 was reported. Tetracyclin
      resistance needs further studies.

PMID- 9567500
TI  - Accuracy of palpation and percussion manoeuvres in the diagnosis of splenomegaly.
AB  - A study was conducted on 80 patients admitted in a teaching hospital to see the
      accuracy of two palpatory methods (Supine palpation and Middleton's manoeuvre)
      and three percussion methods (Traube's space percussion, Castell's and Nixon's
      manoeuvres) in the diagnosis of splenomegaly. Ultrasonographic findings were
      considered as gold standard for diagnosing splenomegaly. Mean age of study
      subjects was 31.5 years and mean Quetelet's index was 17.8 +/- 2.6 kg/m2.
      Sensitivity of Middleton's and Castell's manoeuvres was similar (85.7%) and
      higher than other manoeuvres. Nixon's manoeuvre had the least sensitivity
      (66.7%). Specificity was highest (92.1%) with supine palpation and least (31.6%)
      with Castell's manoeuvre. Supine palpation showed highest positive predictive
      value (91.7%). Receiver Operating Characteristics curves showed greater area with
      middleton's manoeuvre (0.93) followed by supine palpation (0.92), Castell's
      manoeuvre (0.75) and Traube's space percussion (0.74), the findings of the study
      suggests that palpatory methods like Middeton's manoeuvre and Supine palpation
      should be routinely used for diagnosing splenomegaly among non-obese individuals.

PMID- 9567502
TI  - Dyslipidemia: clinical approaches, evaluation of methods and strategies for
      standardization.
AB  - Disorders in lipid metabolism (dyslipidemia) can result to the chronic heart
      disease. The low density lipoprotein (LDL) is a critical subfraction of total
      cholesterol present in serum because it is directly linked to coronary heart
      disease (CHD). The growing awareness of the risks of CHD stipulates the need for
      more accurate and precise measurement of LDL cholesterol. Current approaches in
      diagnosing and monitoring CHD is largely dependent on calculated LDL (CLDL) value
      due to the inherent complexity of ultracentrifugation method. While friedwald's
      calculated formula may provide comparable values with ultracentrifugation method,
      it may provide a result which is different. This difference may be of clinical
      significance. The lipoprotein electrophoresis may be useful in measuring LDL
      cholesterol, in the diagnosis of type III hyperlipidemia (broad beta band) and
      when the triglyceride level exceeds 400 mg/dl. The result that compares the CLDL
      with that obtained by the electrophoresis showed a significant difference (P > or
      = 0.000) for LDL and insignificant difference (P = 0.068) for high density
      lipoprotein (HDL) cholesterol.

PMID- 9567503
TI  - Bone marrow transplantation.

PMID- 9567504
TI  - Right-sided endocarditis following abortion--underdiagnosed condition case
      report.
AB  - We have presented a patient who followed abortion went on to develop septicemia,
      right-sided endocarditis and septic pulomonary emboil. Such potentially fatal
      condition should be prevented and diagnosed early to prevent morbidity and
      mortality.

PMID- 9567505
TI  - Role of Helicobacter pylori in gastric pathophysiology--a review.

PMID- 9567506
TI  - Interobserver variations in clinical signs for diagnosis of pleuritis.
AB  - A study was conducted on 150 patients admitted in a teaching hospital to find out
      reliable clinical signs for diagnosing pleuritis. Cases were selected based on
      suspicion of pleural involvement by history and examination. Final diagnosis was
      made by correlations with radiographic and ultrasonographic reports. Reliability
      of the signs was determined on the basis of high concordance of independently
      observed variations between two medical consultants. Inflammatory involvement of
      pleura was seen in 69.3% cases and 30.7% were due to oedema disorders.
      Concordance between observers was high for crepitations (95.5%) and pleural rub
      (93.8%) followed by vocal resonance (87.6%), dull percussion note (76.9%) and
      mediastinal shift (76.9%).

PMID- 9567507
TI  - Toxocara cati: hatching of second stage larvae.
AB  - A method for hatching second-stage larvae of Toxocara cati is described. Whole
      adult worms are processed by centrifugation in the presence of hypochlorite which
      allows the grinding step to be eliminated. The technique is more rapid and a high
      yield is obtained.

PMID- 9567508
TI  - Biochemical speciation of enterococci causing human infections.
AB  - As Enterococci are now coming up as important nosocomial pathogens, their
      speciation and antibiotic sensitivity testing is important. 120 isolates of
      Enterococci from various clinical samples were physiologically and biologically
      characterised. Speciation on the basis of recommended methods revealed 114(95%)
      as E. faecalis and 6(5%) as E. faecium. Antibiogram of the 120 isolates showed
      that 100(83.3%) were sensitive to Ampicillin. Combination of Penicillin and
      Gentamicin was more effective. E. faecium was more drug resistant.

PMID- 9567509
TI  - The free radicals--the hidden culprits--an update.
AB  - Free radicals are normally produced as a by-product of cellular metabolism. Free
      radicals are capable of killing bacteria, damage biomolecules, provoke immune
      response, activate oncogens, cause atherogenesis and enhance ageing process.
      However, in healthy conditions nature has endowed human body with enormous
      antioxidant potential. Subtle balance exists between free radical generation and
      antioxidant defence system to cope with oxidative stress by various enzymes and
      vitamins at cellular level which prevent the occurrence of disease. However,
      factors tilting the balance in favour of excess free radicals generation lead to
      widespread oxidative tissue damage and diseases. Therefore, trouble starts when
      there is an excess of free radicals and the defence mechanism lags behind.
      Overwhelming production of free radicals in response to exposure to toxic
      chemicals and ageing may necessitate judicious antioxidant supplement to help
      alleviate free radical mediated damage.

PMID- 9567510
TI  - Ancient insights and modern discoveries in the process of aging--an overview.

PMID- 9567511
TI  - Prevention of aging.

PMID- 9567512
TI  - Health and aging.
AB  - Regular meditation is the key to health (mental, physical and social wellbeing).
      It elevates mind from gross level to finer aspect and makes the body and mind
      follow the law of nature achieving good health, preventing disease, improving
      performance and reducing aging process. Balanced diet (less sugar, less salt and
      less fat as age advances supplemented with vitamins and minerals) and mild to
      moderate exercise (walking etc.) are complimentary to the effects of meditation.

PMID- 9567513
TI  - Prevalence of hepatitis C virus (HCV) infection in Mumbai.
AB  - A study was carried out to determine the prevalence of Hepatitis C virus (HCV) in
      Mumbai among certain high risk groups such as renal transplant recipients,
      multitransfused and haemodialysis patients; professional and voluntary blood
      donors and viral hepatitis cases for comparison. Repeated testing of 602 subjects
      for antibodies to HCV using a second generation ELISA assay (Abbott, USA) showed
      an overall prevalence of 16.9%. We found 36.4% of multitransfused patients, 27.8%
      of renal failure cases and 26.2% of renal transplant recipients to be
      seropositive. Voluntary blood donors in our series showed a surprisingly high
      prevalence of 15.9%, and this group needs further investigation. Fifty-six of
      these sera (of which 45 were anti-HCV positive) were tested for HCV RNA by PCR
      and 14(31.1%) of the seropositive samples were also HCV RNA positive. The present
      investigation not only shows a high prevalence of HCV in the study groups but
      also proves the presence of HCV genomes in a significant proportion.

PMID- 9567514
TI  - Microbial profile of pelvic inflammatory disease.
AB  - A total of 100 cases were studied. Fallopian tubes removed at operation
      constituted a very good material to study the infections of upper genital tract.
      Along with fallopian tubes, HVS from same patients were cultured both for aerobic
      and anaerobic organisms. Bacteriological analysis of 100 cases of fallopian tubes
      and same number of HVS showed bacterial growth in 30 cases (30%) whereas in HVS
      samples growth was obtained in 50 cases (50%). In 66.67% of cases same bacteria
      were isolated both from HVS and fallopian tubes which strongly favours the theory
      of ascending infection. Out of all antibiotics ciprofloxacin showed the widest
      spectrum of activity (94.20%). All anaerobes were sensitive to metronidazole.

PMID- 9567515
TI  - Down syndrome associated malformations.
AB  - This paper reports the associated malformations and the clinical findings that
      were observed in 417 cytogenetically confirmed Down Syndrome patients. Among them
      congenital heart defects have occurred more frequently [75; 17.98%] than
      osteoarticular malformations [23; 5.52]; eye anomalies [22; 5.27%]; and
      gastroenterological malformations [n 16; 3.84%]. With regard to prognosis and
      treatment appropriate counselling has been given to Down Syndrome patients and
      their families.

PMID- 9567516
TI  - Mania secondary to alcohol binge.

PMID- 9567517
TI  - Infant feeding practices in urban population--a clinic based study.
AB  - A clinic based cross-sectional study was conducted at Immunoprophylaxis Clinic at
      Govt. Medical College, Nagpur. Mothers of 217 children were interviewed for
      infant feeding practices. In 62.67% of children, breast-feeding was initiated
      within 24 hrs. after birth. About 22% mother used prelacteal feed and 70% mothers
      preferred demand feeding. Prominent area of concern includes discarding of
      colostrum, low exclusive breast feeding rate, delayed weaning and early
      termination of breast feeding. Further improvement in present day infant feeding
      practices is possible by emphasising on the health education component of
      existing nutritional programmes.

PMID- 9567518
TI  - Child health.

PMID- 9567519
TI  - Monkey bites: a public health problem in urban setting.
AB  - Animal bites constitute an important public health problem. Monkey bites
      accounted for 8.8% of total animal bites (1987-1991) treated in Postgraduate
      institute of Medical Sciences, Rohtak. It was noted that monkeys are becoming the
      second most common animal to inflict bites. The hospital data revealed that 63.5%
      of the total animal bites belonged to class-III type. The article also details
      two case studies of monkey bites.

PMID- 9567520
TI  - Epidemiology of group-A streptococcal infection amongst children of different
      ethnic groups in Darjeeling.
AB  - The carrier rate of Group A Streptococcus (GAS) was studied amongst 932 children
      from 1+ upto 12 years of age in three major racial groups in the foothills of the
      Darjeeling district of West Bengal. It was altogether 13 per cent and was found
      to be evenly distributed in the three ethnic groups as Gurkhas: 11 per cent,
      Rajbanshis: 15 per cent and Cosmopolitans: 13 per cent, but the incidence of
      Rheumatic fever and/or Rheumatic heart diseases were unnoticed among the Gurkha
      children who also had significant low ASO titres.

PMID- 9567521
TI  - Community perception about disaster preparedness and response programme in four
      states of India.
AB  - It is well felt that community participation, local planning, development of self
      reliance and manpower resource within the community itself can strengthen the
      effort of disaster preparedness and response. The present study was intended to
      bring out the salient features about perception and opinion of community leaders
      and community members about existing preparedness programme and appropriateness
      of mitigatory exercise against flood disaster in four eastern states of India
      viz. West Bengal, Bihar, Assam and Orissa. Many snags at the implementation
      level, in terms of co-ordination, directives, logistics and knowledge gap were
      noted, which should be dealt with due care for successful disaster preparedness
      programme.

PMID- 9567522
TI  - The relation of exposure to asbestos and smoking habit with pulmonary function
      tests and chest radiograph.
AB  - Environmental cum medical study was conducted in asbestos cement factory. The
      environment was evaluated for asbestos fiber by the methods recommended by BIS.
      Total 355 exposed and 312 suitably matched control workers were investigated by
      spirometer, Wright's peak flow meter and full sized postero-anterior chest
      radiograph. The levels of asbestos fiber were 2 to 3 times higher than TLV i.e. 2
      f/ml in pipe cutting dept., crude fiber grinding inlet count was more than the
      ACGIH recommended limit i.e. 5 mpccf of air in pipe cutting dept. and silica
      mill. In the rest of the department, fiber level as well as dust particle count
      were below prescribed limit. The comparison of mean values of PFT parameters of
      workers with 16-20 years exposure history with control one was showing
      statistically significant decline in mean values of FVC only suggesting
      restrictive type of PFT impairment in this group of workers. But in workers with
      more than 20 years exposure, the mean values of all the parameters studied were
      reduced as compared to control one suggesting combined type of PFT impairment.
      When the mean values of PFT parameters of exposed smokers were compared with
      exposed non-smokers there was statistically no significant difference. This can
      be due to marginal contribution of smoking habit in impairment of PFT parameters
      of exposed smokers. The percentages of workers with parenchymal and pleural
      changes due to asbestos exposure were nearly two times more in more than 20 years
      exposure groups as compared to 11-20 years exposure groups. The parenchymal and
      pleural changes due to asbestos exposure were more common in exposed smokers as
      compared exposed non-smokers. However the detailed analysis revealed that if
      smoking contributes to the development of interstitial fibrosis, the contribution
      is a marginal one in comparison to the effect of asbestos dust exposure.

PMID- 9567523
TI  - National Programme for Control of Blindness--a review.

PMID- 9567524
TI  - An assessment of missed opportunities for immunization in children and pregnant
      women attending different health facilities of a state hospital.
AB  - The present study carried out in Calcutta National Medical College, Calcutta, has
      revealed problem of missed opportunities of immunisation in children and pregnant
      women and factors contributing to the problem. The percentage of missed
      opportunity in children and pregnant woman are 30% and 7% respectively. The major
      cause in case of children were that all the vaccines are not administered in all
      the days of week (71.05%) and in pregnant woman were wrong ideas about
      contraindication (42.86%) and indifferent attitude of the health worker (42.86%).
      All the missed opportunities were attributed to the health care providers.

PMID- 9567526
TI  - Birth asphyxia, Apgar score and neonatal encephalopathy.

PMID- 9567525
TI  - Is there any intersectoral coordination between health and education department
      at primary health center level?
AB  - One of the principles of primary health care is intersectoral co-ordination. A
      cross sectional study done at the primary health center revealed existence of
      unsatisfactory co-ordination between health and education department.

PMID- 9567527
TI  - Clinical and immunological profile of SLE: some unusual features.
AB  - OBJECTIVE: To study the clinical and immunological profile of children with
      systemic lupus erythematosus (SLE). DESIGN: Retrospective hospital based study.
      SETTING: Tertiary level center of North India. SUBJECTS: Sixteen children in the
      age group 4-12 years. METHODS: Medical records of children with SLE were
      analyzed. Clinico pathological features were compared with 2 other series from
      India. RESULTS: Mean age of children at the time of diagnosis was 10 yr and 8
      (50%) children were less than 10 yr of age. The female to male ratio was 7:1.
      Fever (56.2%), rash (87%) and arthritis (87%) were the common clinical
      manifestations, Renal involvement was noted in 56.2% of cases. Other clinical
      features included hemolytic anemia (31.2%), thrombocytopenia (18.6%) and
      Raynaud's phenomenon (12.5%). Cardiac involvement in the form of severe
      myocarditis and endocarditis occurred in one patient each. Pulmonary hypertension
      was the presenting feature in one child with right heart failure. One child had
      multiple sclerosis along with SLE--a rare combination. ANA positivity was seen in
      all children. Five children died; two had severe cardiac involvement. Three
      children had renal involvement and one died of pulmonary hypertension. Two-thirds
      of subjects with renal involvement improved after therapy according to NIH,
      Bethesda protocol. CONCLUSIONS: SLE must be considered in any child with
      multisystem disease, as the disease may have certain unusual presentations.

PMID- 9567528
TI  - Seasonal pattern of morbidities in preschool slum children in Lucknow, north
      India.
AB  - OBJECTIVE: To quantify the burden of common morbidities for each month in one
      year, in preschool children. SETTING: Anganwadi centers under the Integrated
      Child Development Services Scheme (ICDS) in Lucknow, North India. DESIGN:
      Prospective cohort study, METHODS: From 153 anganwadi centers in urban Lucknow,
      32 were selected by random draw. All eligible children registered with the
      anganwadi worker were enrolled over a period of six months from July 1995 to
      January 1996. All the subjects were then contacted a second time six months
      later. SUBJECTS: There were 1061 children (48.3% girls and 51.7% boys) between
      the ages of 1.5 to 3.5 years. RESULTS: The annual incidence rate (IR) per 100
      child-years for respiratory, diarrhea and skin diseases and pneumonia were 167,
      79.9, 30.6 and 9.6, respectively. When compared to other seasons, the IR of
      pneumonia was lowest in the winter months (October to February) while those of
      diarrhea and skin diseases were the highest in summer (March-June) and monsoon
      (July to September) months, respectively. Season specific diseases were measles
      in summer, and fever as the isolated symptom in monsoon. The IR for combined
      morbidities was the highest in the monsoon as compared to winter months.
      CONCLUSIONS: Season specific intensification of existing health care resources
      for these morbidities can be considered. Similar studies are needed from other
      parts of the country.

PMID- 9567529
TI  - A prospective cohort study on the survival experience of under five children in
      rural western India.
AB  - OBJECTIVE: To study the role of birth weight, nutrition, immunization and other
      medical as well as social factors in determining child survival. DESIGN: A
      prospective cohort study. SETTING: 45 villages in Shirur Development Block in
      Pune District in Maharashtra. METHODS: A cohort of 4129 children were followed
      from birth till 5 years of age. Weight and length/height of the child was
      measured at birth and at 3 monthly home visits. Information was also obtained on
      common childhood morbidities, immunization status and other bio-medical factors.
      Cause of death was ascertained by verbal autopsy. RESULTS: The neonatal, infant
      and underfive mortality was rates were estimated to be 37, 60 and 79 per 1000
      live births, respectively. Diarrhea and ARI contributed to the major mortality
      burden. The Kaplan Meier Survival curve showed a sharp fall in the neonatal
      period, a less rapid decline in the post-neonatal period followed by a marginal
      fall in the post-infancy period till 5 years age. Girls had a better survival in
      the early neonatal period but the trend reversed in the late neonatal period.
      Normal birth weight children had better survival curves compared to low birth
      weight children. Survival improved with increasing birth order. Multivariate
      analysis revealed that birth weight, immunization status, and mother's and
      child's nutritional status influenced infant and under five mortality.
      CONCLUSION: Birth weight continues to exert its influence not only on
      survival/mortality in early life but even as late as 5 years of age. Strategies
      to improve child survival should include immunization and breastfeeding.

PMID- 9567530
TI  - Management of nephrotic syndrome.

PMID- 9567531
TI  - Examination reform at the grassroots: teacher as the change agent.

PMID- 9567532
TI  - Evaluation of training programme for traditional birth attendants in newborn
      care.

PMID- 9567533
TI  - High risk factors for development of retinopathy of prematurity.

PMID- 9567534
TI  - Transfusion malaria in sick neonates.

PMID- 9567535
TI  - Carotenoderma in metabolic carotenemia.

PMID- 9567536
TI  - Ectopic bronchogenic cyst.

PMID- 9567537
TI  - Importance of etiologic diagnosis of hydrocephalus as illustrated by a case of
      Walker Warburg syndrome.

PMID- 9567539
TI  - Images in Clinical Practice. Caffey's disease.

PMID- 9567538
TI  - Neonatal morbidity and mortality: report of the National Neonatal-Perinatal
      Database.

PMID- 9567540
TI  - DPT-OPV immunization and sudden infant death syndrome.

PMID- 9567541
TI  - Lipoprotein-lipase deficiency.

PMID- 9567542
TI  - Pulmonary agenesis.

PMID- 9567543
TI  - Status of poliomyelitis--1996 after "pulse polio immunization programme" sentinel
      center experience.

PMID- 9567545
TI  - Consumer Protection Act and medical profession.

PMID- 9567544
TI  - Splenic infarct in falciparum malaria.

PMID- 9567546
TI  - Caesarean sans pediatrician!

PMID- 9567547
TI  - Effect of long-term treatment with antiepileptic drugs on serum lipids.

PMID- 9567548
TI  - The paroxysmal cough in pertussis can be extremely distressing.

PMID- 9567549
TI  - Acute respiratory infections in developing countries: current status and future
      directions.

PMID- 9567550
TI  - Current spectrum of hepatobiliary disorders in northern India.
AB  - OBJECTIVE: To evaluate the current spectrum of hepatobiliary disorders in
      children in Northern India. SETTING: Tertiary level referral hospital. METHODS:
      All children with hepatobiliary disorders presenting between January 1992 through
      July 1995 were evaluated by clinical assessment, liver function tests, viral and
      autoimmune markers, liver biopsy, copper studies and other relevant
      investigations. RESULTS: Two hundred and thirty five children with hepatobiliary
      disorders were seen over three and a half years period (67 cases per year). Acute
      hepatitis (28%), chronic liver disease (36%) and neonatal cholestasis syndrome
      (NCS) (26%) were the most common patterns of liver diseases. Chronic liver
      diseases were constituted by ICC (2%), post-hepatitic etiology (13%), Wilson's
      disease (21%), autoimmune (4%), non-Wilsonian metabolic diseases (16%), hepatic
      venous outflow obstruction (2%) and non-cirrhotic portal fibrosis (1%). Cirrhosis
      was documented in 71% and chronic hepatitis in 12% of cases with chronic liver
      disease. Fulminant hepatic failure was the presentation in 4% of children with
      liver diseases. CONCLUSION: Chronic liver diseases in Northern India are mainly
      constituted by post hepatitic, metabolic and cryptogenic etiology and ICC is
      rarely encountered. NCS is also one of the major subgroups of liver diseases in
      children.

PMID- 9567551
TI  - Multi-drug resistant typhoid fever with diarrhea.
AB  - OBJECTIVE: To provide information about the characteristics of diarrheal stool in
      multi-drug resistant typhoid fever and observe the clinical course after
      treatment with furazolidone or ciprofloxacin. SETTING: Hospital based. SUBJECTS
      AND METHODS: Twenty one male children who were positive for multi-drug resistant
      S. typhi by blood and stool cultures, having diarrhea at the time of
      hospitalization comprised the subjects. Serum and stool electrolytes were
      estimated. Stool samples were also processed to detect established
      enteropathogens, leukocytes and red blood cells. Children were treated either
      with furazolidone or ciprofloxacin and evaluated till recovery. RESULTS: Mean (+/
      SD) pre-admission duration of fever and diarrhea of these cases were 19.1 (+/-
      5.6) and 15.8 (+/- 4.6) days, respectively. Stool character in 81% of the
      patients was watery with mean (+/- SD) volume of stool 51.4 (+/- 25.1) ml per kg
      body weight in the first 24 hours of observation. Leukocyte count varied between
      20-49 per high power field in 66.7% stool samples. Occult blood was present in
      only 19% cases. Fecal red blood cells in high power field were detected in 52.4%
      cases. Mean fecal electrolytes (mmol/liter) were as follows: sodium-53.8,
      potassium-51.4, chloride-41.6 and total CO2-24.3. Most of the children (71.4%)
      had no dehydration and had normal serum electrolytes. The isolated strains of S.
      typhi were multi-drug resistant. These children were treated successfully either
      with furazolidone or ciprofloxacin. CONCLUSION: The stools of multi-drug
      resistant typhoid fever patients were watery with little blood. Their electrolyte
      contents were more similar to the diarrheal stool seen in shigellosis rather than
      cholera. Uncontrolled observations revealed that children recovered with
      furazolidone or ciprofloxacin therapy.

PMID- 9567552
TI  - Longitudinal study of human milk creamatocrit and weight gain in exclusively
      breastfed infants.
AB  - OBJECTIVE: To determine the creamatocrit values of breastmilk at different
      lactational periods during the first 6 months after delivery and its relation to
      infant growth. DESIGN: Prospective follow-up study. SETTING: Maternity and well
      baby clinics of a metropolitan teaching, a rural teaching and a suburban
      municipal hospital. SUBJECTS: 1322 exclusively breastfed infants and their
      mothers. There were 160 preterm, 281 term low birth weight (LBW) and 881 term
      appropriate for date (AFD) babies. METHODS: Creamatocrit of breastmilk and
      infant's body weight were recorded at 4,8,12,16,20 and 24 weeks after birth.
      RESULTS: Creamatocrit values of breastmilk in all mothers increased upto 16 post
      partum weeks and then declined. There were no significant differences in
      creamatocrit values of breastmilk of mothers of preterm, term LBW and term non
      LBW infants. Preterm and term LBW infants showed a catch up in body weight with
      the term AFD group by 20 weeks post-partum. CONCLUSIONS: The breastmilk
      creamatocrit progressively rises upto the fourth month of lactation but is not
      influenced by gestation or intra uterine growth retardation. There is no
      relationship between breastmilk creamatocrit and infant growth. Exclusive breast
      feeding adequately supports growth of LBW infants in comparison to their normal
      peers during the first 6 months of life.

PMID- 9567553
TI  - Newer hepatitis viruses.

PMID- 9567554
TI  - Integrated Child Development Services Programme--need for reappraisal.

PMID- 9567555
TI  - Validation of revised prescreening Denver Questionnaire in preschool children of
      urban slums.

PMID- 9567556
TI  - Tobacco use in rural Indian children.

PMID- 9567557
TI  - Hepatic profile in asphyxia neonatorum.

PMID- 9567558
TI  - Catastrophic WPW syndrome in a 13-month child: cure by radiofrequency ablation.

PMID- 9567559
TI  - Pulmonary veno occlusive disease.

PMID- 9567560
TI  - Galactosemia with rubella infection.

PMID- 9567561
TI  - Reiter's syndrome.

PMID- 9567562
TI  - Images in clinical practice. Progeria.

PMID- 9567563
TI  - A cheap alternative to a stadiometer and an infantometer.

PMID- 9567564
TI  - A cheap alternative to a stadiometer?

PMID- 9567565
TI  - Infantile spasms.

PMID- 9567566
TI  - Minimum inhibitory concentration of furazolidone in children with typhoid fever.

PMID- 9567567
TI  - Resurgence of epidemic dropsy.

PMID- 9567568
TI  - Medical management of hypertrophic pyloric stenosis.

PMID- 9567569
TI  - Of the two generally available diagnostic tests for childhood tuberculosis,
      namely, Mantoux and BCG, which is better?

PMID- 9567570
TI  - Ethnic identities, food and health.

PMID- 9567571
TI  - Dietary intakes among Siberian Yupiks of Alaska and implications for
      cardiovascular disease.
AB  - We describe dietary intake for 65 Siberian Yupik residents of Gambell, AK using
      24-h recalls and annual food frequencies collected in October 1992. The
      objectives were to describe dietary characteristics important in risk of
      cardiovascular disease, determine the extent that their diet differs from the
      diet of general US and northern populations, assess how the diet met national
      guidelines for the prevention of cardiovascular disease, and propose dietary
      recommendations. Compared to US intakes in general (NHANES III), intakes of
      Siberian Yupiks expressed as percent of energy were: 8-10% higher in fat, 6%
      higher in protein, 5-7% higher in monounsaturated fats and 12-15% lower in
      carbohydrate. Energy from saturated and polyunsaturated fats was similar (11% and
      8% respectively). Cholesterol intakes were not significantly different. Mean
      intakes of selenium, a-topocopherol, folacin (men), and vitamin C (men) met
      Recommended Dietary Allowances, which may contribute to cardiovascular health.
      Mean intake of n-3 fatty acids (7.0 g/d), twice the 3 g/d associated with
      favorable effects, was comparable with intake of Greenlandic Eskimos. Dietary
      risk factors included high intakes of % energy from fat and saturated fat, and
      low intakes of fiber. Native foods were important sources of monounsaturated
      fats, n-3 fatty acids and selenium.

PMID- 9567572
TI  - Hypolactasia in the indigenous populations of northern Russia.
AB  - The distribution of hypolactasia (PH) in the indigenous populations of the polar
      and related territories of the Russian Federation was investigated by an oral
      lactose tolerance. The frequency of hypolactasia in Kildin Saami population is
      48%, Komi-Izhem-63%, Northern Mansi-71%, Northern Khanty-72%, West Siberia Nenets
      78%. Generally hypolactasia frequencies in indigenous groups of Arctic and Sub
      Arctic territories of Russia are higher than in the "reference" samples of Slav
      (Russian, 40-49%) and Permian Finn (Komi-Permiak and Udmurtian, 50-59%) groups.

PMID- 9567573
TI  - Fatty acid composition in serum among males 4-16 years after myocardial
      infarction.
AB  - In a case-control study we compared men who had suffered a myocardial infarction
      with age-matched controls free from clinically apparent ischemic heart disease.
      Our main interest were differences in serum lipid and apolipoprotein
      concentrations. We found no significant differences between these two
      populations. The fatty acid composition of the serum cholesterol esters was
      studied as an indirect measure of the dietary fat quality. There were rather
      small differences with regard to the fatty acid composition between the survivor
      cases and the controls suggesting that the quality of the dietary fat was not
      better among the cases after the myocardial infarction than among the average
      male in Kiruna. The cases had a significantly higher proportion of palmitoleic
      acid (16:1 n-7, p < 0.004) than the controls, also after controlling for other
      biomedical risk factors. A high content of palmitoleic acid may be a marker of
      increased risk for coronary heart disease.

PMID- 9567574
TI  - Nasopharyngeal bacteria found on blood agar plates from healthy children in
      Greenland.
AB  - We have systematically studied the aerobic nasopharyngeal bacteria isolated from
      swabs by unselective subculturing on 5% horse blood agar and chocolate agar in 70
      healthy children aged 0-1, 3-5 and 8 years in Nuuk and Sisimiut, Greenland. The
      purpose was to provide a basis for a better understanding of the infectious
      pathology and blind antibiotic treatment against potential pathogens thereby
      improving standard antimicrobial treatment of upper respiratory tract infections
      (URTI) and otitis media (OM) among children in Greenland. The study serves also
      as a baseline for future microbiological and immunological research projects. The
      children were clinically examined for any infectious diseases and a medical
      history was obtained which allowed for selection of children without a history of
      severe clinical infection. Nasopharyngeal swabs obtained via the oral route were
      instantly spread on 5% blood agar and chocolate agar culture plates and incubated
      aerobically. Subsequently, potentially pathogenic as well as non-pathogenic
      bacteria were identified by conventional methods. Healthy children in Greenland
      carry grossly the same aerobic bacterial flora as children in other parts of the
      world but potentially pathogenic bacteria were found in very high frequency
      (94%). Staphylococcus aureus, Streptococcus pneumoniae and Moraxella catarrhalis
      were found in higher frequencies in the youngest children. Haemophilus influenzae
      non-b was found in high frequencies in all age groups (67-76%). H. influenzae
      type b was carried by 11.4%. Group A streptococci were found more frequently in
      older children and in children from Sisimiut. Of M. catarrhalis strains 88%
      produced beta-lactamase. Neisseria meningitidis, Mycoplasma pneumoniae and
      chlamydiae were not detected at all. The high carrier frequency of potentially
      pathogenic bacteria in healthy children in Greenland may be related to the high
      frequency of URTI's and episodes of OM among children in Greenland.

PMID- 9567575
TI  - Uses of mushrooms by Finns and Karelians.
AB  - Finns have adopted two traditions of mushroom use: one, the old Roman tradition,
      came through France and Sweden to the educated, mostly Swedish speaking people of
      southwest Finland; the other came from the east via Karelia and was adopted by
      ordinary country folk. This eastern tradition is still maintained among the
      Karelinas living in Tver government in Russia. Even the use of Amanita muscaria
      for killing flies is still utilized there. The western tradition favoured
      chanterelles and Boletus edulis, the eastern acrid milk caps, the Lactarius
      species. During the famines in the 1860's and after the World War II the
      government authorities tried to promote the use of wild mushrooms, but the real
      impulse to a more versatile mushroom use was initiated after the war when 400,000
      evacuees from that part of Karelia conquered by the Soviet Union were resettled
      among farming families all over Finland. In 1969 the National Board of Forestry
      began to train mushroom advisors, a programme which still continues. In 1981
      Finland passed a statute on edible mushrooms and drew up a list of commercial
      species. Even today the largest percentage of marketed mushrooms comes from
      Eastern Finland and the Lactarius tivialis species sells best. Gyromitra
      esculenta, the false morel is considered a delicacy. Today picking mushrooms is a
      passionate hobby for many Finns.

PMID- 9567576
TI  - Psychological adaptation to the polar environment.
AB  - Until the 1950's, psychological adaptation to the polar regions was expressed by
      survivors more in terms of their endurance and heroism after the event than by
      any studied preparation beforehand, a careful monitoring of performance in situ,
      the follow-up of subjects afterwards, and a scholarly comparison of data-based
      research finding. This paper covers some of the omissions, and presents the
      results of a few studies that should be of value to the variety of people who for
      quite different periods and purposes visit polar regions. Because of the author's
      own background in Antarctic research it draws upon material collected in
      Antarctica, but it also includes empirical studies made by behavioural scientists
      in the Arctic. Its aim is to encourage potential venturers to the polar areas to
      prepare themselves mentally as well as physically and logistically for the task
      ahead of them, whether it be for the long winter night at base or for the long
      summer day in the field. It concludes with a plea for all the venturers to accept
      an obligation to provide research data on themselves. The outcome, if done
      systematically, could be of value both for future participants and for
      behavioural scientists, because in the past human factors in exploration have
      been given little attention.

PMID- 9567577
TI  - Toward a new paradigm in substance abuse and other problem behavior prevention
      for youth: youth development and empowerment approach.
AB  - The purpose of this article is to 1) address a paradigm shift taking place in the
      field of substance abuse prevention directed for youth and 2) to introduce an
      innovative approach to substance abuse and other problem behavior prevention that
      reflects this shift in prevention paradigm. The new path introduced is youth
      development and empowerment (YD&E) approach. In order to establish a conceptual
      foundation for this approach, this article 3) reviews the theoretical advances
      made in the field of substance abuse prevention during the last three decades.
      This is followed by a conceptualization of the processes of implementing the YD&E
      program by 4) specifying the mechanism used for the empowering processes and by
      5) identifying the structural components of the youth empowerment model that
      serve the empowering processes. It is hoped that this article serves as a conduit
      for an improved approach to adolescent substance abuse prevention and youth
      development that goes beyond, rather than against, the traditional risk-factor
      approach. In this new approach, youths are viewed as assets and resources to our
      community rather than social problems or community liabilities. The organizing
      concept of this new paradigm is: social, economic, and public opportunity denied
      to youth is equal to social problems imposed on youth by adults.

PMID- 9567578
TI  - Alcohol dependence in adult children of alcoholics: longitudinal evidence of
      early risk.
AB  - This study investigates familial alcoholism effects and the comparative
      probability of risk for alcohol dependence in adult children of alcoholics (ACAs)
      with a control group of non-ACAs. A cohort of 12,686 young adults from the
      National Longitudinal Survey of Youth (NLSY) is examined over a five-year period
      and conventional and lineal intergenerational models of alcoholism transmission
      are assessed. The results of multivariate logistic regression analyses indicate
      that the risk is relatively greater for male ACAs; sons of alcoholics drink
      significantly more heavily, experience problems earlier, and develop alcohol
      dependence more extensively than female ACAs or non-ACAs of either gender. The
      extent of dependence found in subjects with a lineal history of alcoholism on the
      father's side of the family, as well as heavy drinking, cigarette smoking and
      drinking onset in adolescence should be considered as critical predisposing
      factors of high risk for dependence at later ages. These observations corroborate
      clinical studies and support a growing body of biopsychosocial research
      literature.

PMID- 9567579
TI  - Training school counselors in substance abuse risk reduction techniques for use
      with children and adolescents.
AB  - A training project prepared school counselors for expanded roles in the
      prevention, early detection, and appropriate referral of students at high risk of
      substance abuse. The project trained middle and high school counselors to work as
      facilitators of support groups for students at greatest risk for substance abuse;
      the results were: 1) greater perceived self-efficacy, comfort, confidence, and
      competence by counselors as a result of Initial, Experiential, and Concurrent
      training, and 2) improved ability to use group counseling techniques as a result
      of training.

PMID- 9567580
TI  - Evaluating outcomes in a substance abuse training program for Southeast Asian
      human service workers: problems in measuring change cross-culturally.
AB  - The following article describes the evaluation challenges faced in a cross
      cultural substance abuse training program. Non-Southeast Asian instructors
      designed and taught courses for Cambodian and Vietnamese human service workers
      over a two-year period. Although cultural considerations were a central focus in
      the design of the program, instructors underestimated the difficulty of modifying
      standard questionnaires for use with Southeast Asian participants. As a
      consequence, the formal evaluation process had limited benefit but several
      insights were gleaned through alternative evaluation methods.

PMID- 9567581
TI  - A family based model of Hispanic adolescent substance use.
AB  - While adolescent substance use has been the focus of extensive research over the
      last few decades, Hispanic adolescent substance use has received only limited
      attention. Studies exploring predictors of Hispanic adolescent substance use have
      failed to adequately explore the contribution of the family on substance use. The
      present study examined the relative influence of family, school and peer
      influences, perceived student substance use, family substance use, and
      acculturation on a sample of Mexican-American early adolescents using structural
      equations modeling. The findings varied for males and females. Family functioning
      and family use directly influenced substance use for males. Family functioning
      influenced school and peer variables, however, these were unrelated to use. For
      females, family use and student use directly influenced substance use. Family
      functioning influenced family use and school and peer attachments. School and
      peer attachment predicted perceived student use. These findings suggest that
      family functioning has a primary role in Hispanic adolescent substance use.

PMID- 9567582
TI  - Calcium channel blockers--under a cloud?

PMID- 9567583
TI  - Mast cell count in surgically resected appendices.
AB  - Two hundred appendices were studied for mucosal and submucosal mast cell counts.
      In histologically normal appendices mucosal mean mast cell count (47.63/sq mm)
      was more than submucosal mean mast cell count (44.27/sq mm). Those patients who
      were aged under 15 and above 46 years showed more mean mucosal mast cell count
      compared to others. In acute appendicitis both mucosal and submucosal mast cells
      were decreased and in subacute appendicitis their count was found to be
      intermediate between normal and acute appendicitis.

PMID- 9567584
TI  - A clinicopathological study of infections in burn patients and importance of
      biopsy.
AB  - Thirty-four patients with burns were subjected to the clinicopathological study
      with special reference to culture of the wound and histological examination of
      the burned tissue. The commonest cause of burn was thermal burn (91.18%) followed
      by electric burn (5.88%) and chemical burn (2.94%). The maximum number of
      patients belonged to second and third decades of life (61.78%). Females were
      commonest victims, with male:female ratio was 1:1.6. On the 1st to 3rd postburn
      day (PBD) most of the wound remained sterile and Strept haemolyticus was first
      bacteria isolated on 1st PBD. Gram-positive and Gram-negative bacteria, specially
      pseudomonas, invaded the burn wound as early as 3rd PBD, it was more so with the
      patients of extensive burn. Among the Gram-positive bacteria Staph aureus was
      most notorious and invaded burn wound very early. Pseudomonas had maximum growth
      followed by klebsiella and Esch coli, multidrug resistance was more common with
      pseudomonas. Among the fungal infections Candida albicans had maximum incidence.
      Positive blood cultures for bacteria were seen during 2nd, 3rd and 4th postburn
      weeks. Pseudomonas was the commonest bacteria isolated. Biopsies were done in 17
      patients and showed maximum incidence of bacterial infection followed by fungal
      infection. Patients with burn more than 60% of total body surface area (TBSA) had
      100% mortality, while patients with 20-30% of TBSA burn had 20% mortality, the
      overall mortality was 50%. Biopsies of the burn wound played an important role in
      the accurate diagnosis and thus helped in starting early specific therapy to
      prevent death from sepsis.

PMID- 9567586
TI  - Diagnostic significance of excretory urography and ultrasonography in renal
      diseases.
AB  - A comparative study of intravenous urography (IVU) and ultrasonography (USG) was
      performed in 100 patients of all age groups, having symptoms and signs of various
      renal diseases. Sonography was found to be 100% sensitive and diagnostic in
      approximately 74% of renal pathologies included in this study, namely calculous
      disease (excluding midureteric calculi), obstructive lesions of pelvicalyceal
      system (PCS), cystic diseases, gross congenital lesions, traumatic lesions and
      neoplasms. It also provided information about the complications of long standing
      obstruction to PCS such as non-functional and atrophied kidneys, infection, etc.
      IVU proved better in midureteric calculi (100%), 88.2% of all congenital lesions
      including the major as well as minor variations. Both modalities proved to be of
      poor help in diffuse parenchymal diseases (IVU-40% and USG-50%) and renal
      tuberculosis (IVU-18.2% and USG-45.5%). Sonography was able to delineate the
      cause of obstruction to PCS in only 72.3% of cases as compared to 88% by IVU.

PMID- 9567585
TI  - Infant feeding and weaning practices in some semi-arid rural areas of Rajasthan.
AB  - The paper contains information on infant feeding and weaning practices in the
      rural communities of a semi-arid district of Rajasthan. The findings have been
      drawn from a recent survey of 328 rural mothers. The rural women of this area are
      found to believe in old deep seated beliefs and customs, which in turn deprive
      their infants from advantages of colostrum (77% discarded colostrum) and
      nutritionally rich supplements, which otherwise should be supplemented to them at
      any cost in order to keep them healthy. The practices of prolonged breast feeding
      and delayed supplementation to infants are rampant in this area. Mean age at
      weaning (27.1 months) again not only affects the health status of mothers and
      their children but also leads to the undernutrition among both. The findings of
      the study necessitate to evolve an exhaustive educative programme dealing with
      various aspects of infant feeding and weaning practices, keeping in view their
      traditions, so that the useful practices can be encouraged and harmful ones be
      prohibited.

PMID- 9567587
TI  - Cystoscopic staging of carcinoma uterine cervix, revisited.
AB  - Of the 378 cases of stage 3 carcinoma uterine cervix, only 10 showed vesical
      invasion, while 19 of 24 cases of stage 4 disease had vesical invasion. Results
      of this procedure did not alter the management of the disease in any of these
      cases. From the whole series it was concluded that cysto-urethroscopy is an
      unnecessary, cost ineffective, invasive procedure which has no role in either
      diagnosis or in planning the definitive treatment of carcinoma uterine cervix.

PMID- 9567588
TI  - Ultrasonically guided percutaneous drainage of breast abscess.
AB  - Percutaneous drainage of abscess under ultrasound guidance is a well established
      modality. Its use in breast abscess has still not found wide application. The
      present study on 25 consecutive cases of breast abscess with success rate of 84%
      is an attempt to recommend routine use of this modality wherever the facilities
      exist.

PMID- 9567590
TI  - Irritable bowel syndrome.

PMID- 9567589
TI  - Serodiagnosis and immune profile in rheumatoid arthritis.
AB  - One hundred and seventy-five cases of clinically diagnosed rheumatoid arthritis,
      82 non-rheumatoid cases suffering from various other diseases and 40 healthy
      normal controls were investigated for detection of rheumatoid factor,
      quantitation of serum immunoglobulin, demonstration of antinuclear antibody (ANA)
      and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid
      factor (RF) showed 64% positivity in rheumatoid group and 1.2% positivity in non
      rheumatoid group. All three immunoglobulins (IgG, IgM, IgA) were found to be
      raised in serum of patients with rheumatoid arthritis, whereas only IgA level was
      elevated in serum of patients with non-rheumatoid diseases. ANA and LE cell
      phenomenon were observed in 3.4% and 2.8% cases respectively in cases of
      clinically diagnosed rheumatoid arthritis who had been suffering from severe
      active rheumatoid arthritis. In non-rheumatoid group RF was positive in
      significant titre in only one case of leprosy. Synovial fluid and synovium were
      found to be heavily infiltrated by plasma cells and lymphocytes. RF appears first
      in synovial fluid and then in serum. Hence RF titre in blood may not attain
      significant level for the first several months.

PMID- 9567591
TI  - Medical conferences: present status and suggestions for the future.

PMID- 9567592
TI  - Gestational diabetes mellitus becoming insulin-dependent diabetic following
      hepatitis B virus infection.

PMID- 9567593
TI  - Beta-blocker in acute coronary insufficiency.

PMID- 9567594
TI  - Measles, mumps, rubella vaccine induced subacute sclerosing panencephalitis.

PMID- 9567595
TI  - Approach to aerosol therapy in management of asthma at primary care level.

PMID- 9567596
TI  - Medical practitioners in private sector and prevention and control of infectious
      diseases.

PMID- 9567597
TI  - Changing profile of diabetic ketosis.
AB  - Forty-three cases of diabetic ketosis were analysed to determine the mode of
      presentation, treatment modalities and outcome. Among these cases 62.8% were non
      insulin dependent diabetes mellitus (NIDDM) patients and 37.2% belonged to the
      insulin dependent diabetes mellitus (IDDM) group. Six patients had blood glucose
      levels of more than 250 mg/dl but less than 300 mg/dl who were grouped separately
      for analysis under the term "euglycaemic diabetic ketoacidosis (EGDK)". Infection
      was the commonest precipitating factor in diabetic ketosis in all groups.
      Abdominal pain and vomiting occurred with NIDDM and EGDK cases. Drowsiness was
      common and coma was rare. Acute myocardial infarction (MI) and pulmonary oedema
      occurred with NIDDM cases. Shock, acidosis, acquired respiratory distress
      syndrome (ARDS) and mucor mycosis were seen with IDDM cases. Mortality was 7 out
      of 43(16.3%). Saline requirement was lower in NIDDM and EGDK cases. Intensive
      insulin therapy with hourly intravenous doses were needed for IDDM cases while
      majority of NIDDM cases could be managed with 6 hourly doses of insulin given
      subcutaneously or intramuscularly.

PMID- 9567598
TI  - Effect of antihypertensives on plasma potassium in end stage renal disease: a
      retrospective study.
AB  - The antihypertensive drug therapy and the peri-operative plasma potassium trend
      in end stage renal disease (ESRD) patients undergoing renal transplant were
      analysed. Out of consecutive 107 live related donor renal transplant, complete
      data available for 74 patients between June 1991 and March 1993, were entered in
      proforma and analysed. On the basis of antihypertensive or no antihypertensive
      drugs prescribed, patients were grouped in 6 categories. Group I patients taking
      no antihypertensives were taken as control. All patients were comparable for
      their age, sex, weight, immunosuppressive therapy, anaesthetic and fluid
      management during surgery. At the time of induction of anaesthesia, patients
      taking atenolol (plasma K+ levels being 5.34 +/- 0.75 mmol/l in group II and 5.44
      +/- 0.63 mmol/l in group III) or captopril (serum K+ level being 5.05 +/- 0.94
      mmol/l in group V) in combination with nifedipine and with or without clonidine
      had significant hyperkalaemia than the patient without antihypertensives (serum
      K+ level being 4.49 +/- 0.71 mmol/l). Patients, on these two antihypertensives,
      frequently needed active treatment of alarming hyperkalaemia (blood K+ more than
      5 mmol/l and tall 'T' wave in lead II) and cardiac arrhythmias. In conclusion,
      ESRD patients taking atenolol or captopril are needed to be frequently monitored
      for blood potassium levels and it would be advisable to avoid these drugs to
      control hypertension in ESRD patients, especially, when scheduled for renal
      transplantation.

PMID- 9567599
TI  - Diabetes in acromegaly--a study of 34 cases.
AB  - The incidence and severity of diabetes mellitus (DM) in 34 patients with
      acromegaly were studied. The incidence was higher (55.9%) than any other series
      reported. Nineteen had DM, of which 10 were symptomatic. Only one had diabetic
      retinopathy. Glucose tolerance was improved after successful treatment of
      acromegaly.

PMID- 9567600
TI  - Hypertensive disorders of pregnancy and maternal and foetal outcome: a case
      controlled study.
AB  - A case controlled prospective study of 250 cases of hypertension complicating
      pregnancy (study group) and 400 normal pregnant women (control group) was carried
      out to determine the effect of hypertension on maternal and foetal outcome.
      Pregnancy induced hypertension was present in 96% cases and chronic hypertension
      in 4% cases. Preterm delivery (28.8% versus 3%), labour induction rate (52.8%
      versus 3.25%), caesarean section rate (14.8% versus 3.5%), stillbirth rate (4.8%
      versus 0.25%) and overall perinatal mortality rate (14.8% versus 1%) were higher
      in study group compared to controls. In study group (40%) babies required special
      nursery care compared to controls (6.75%). From these results it can be concluded
      that maternal hypertension is associated with adverse pregnancy outcome.

PMID- 9567601
TI  - Association of cerebral palsy with epilepsy.
AB  - Fifty patients of various types of cerebral palsy were studied to find out an
      association between cerebral palsy, EEG abnormalities and development quotient.
      Seventy-six per cent patients had spastic cerebral palsy. Hypotonic cerebral
      palsy was the next common type (14%). Athetosis and ataxic forms were found to be
      rare (2% each). Epilepsy was associated with 56% patients. Clinical types of
      seizures observed were: Generalised tonic-clonic (43%), myoclonic (17.9%),
      generalised tonic (10.7%), partial simple (10.7%) and partial complex (17.9%).
      The incidence of seizures was highest in hypotonic type in which 85.7% had
      epilepsy. Mean developmental quotient of cerebral palsy patients was 34.9% with
      maximum retardation in hypotonic cerebral palsy (25.14%). Sixty per cent of
      patients had abnormal EEG, out of these hypotonic patients had maximum (70%)
      chances of EEG abnormality followed by spastic patients (55%). Developmental
      retardation was more severe statistically in the patients with abnormal EEG than
      normal EEG.

PMID- 9567602
TI  - Simple renal cyst: an observation.
AB  - In the present study 1500 patients having abdominal ultrasonography were
      included. Unsuspected renal cysts were detected in 76 patients (5.06%). The age
      range was between 8 and 86 years with a maximum incidence being at 41-60 years
      age group. These asymptomatic cysts were observed commonly in the upper pole of
      right kidney. Incidence as well as size increased with age. Usually these cysts
      do not require any surgical intervention unless complicated.

PMID- 9567603
TI  - Abdominal hysterectomy: a new approach for young gynaecologists.
AB  - Abdominal hysterectomy is performed for various gynaecological conditions. During
      operative procedures haemorrhage caused by trauma or slipping and retraction of
      uterine or ovarian artery has been a cause of great concern to gynaecologists
      specially in absence of adequate blood transfusion facilities. To overcome this
      problem, a new approach has been developed--ligation of the uterine artery and
      ovarian artery (in case of salpingo-oophorectomy) before going for conventional
      hysterectomy procedures. Abdominal hysterectomy was performed in 500 cases during
      last 7 years. Traumatic injury to left uterine vessels was seen in 2 cases
      (0.4%). No other injury to ovarian vessels, right uterine vessels, ureter and
      bladder was observed. Hence it is concluded that ligation of uterine artery,
      prior to conventional abdominal hysterectomy procedures, is an extremely safe
      procedure reducing the risk of haemorrhage and thus allowing young gynaecologists
      to perform this operation with less fear and more confidence.

PMID- 9567604
TI  - Epidemic acute conjunctivitis.

PMID- 9567605
TI  - Role of nitric oxide in health and disease.

PMID- 9567606
TI  - Creutzfeldt-Jakob disease: report of a case from West Bengal.

PMID- 9567607
TI  - [Total intravenous anesthesia in neurosurgery. Our clinical experience].
AB  - BACKGROUND: The quality of a "neuroanesthetic" technique is the result of its
      pharmacokinetics, of its effect on intracerebral homeostasis and metabolism, of
      its antinociceptive and neuroprotective features. Aim of this study is to test
      the effectiveness of TIVA as the technique of choice in neurosurgical patients
      throughout a retrospective analysis of 1982 patients scheduled for brain tumors,
      neurovascular surgery and spine lesions. METHODS: 1982 patients (1023 F, 959 M),
      ASA I-IV, aging 15-80 yrs scheduled for neurosurgery were studied. Hemodynamic
      and electrophysiological parameters were monitored carefully. Time of recovery
      was evaluated although this parameter is influenced by perioperative clinical
      status and by area and kind of brain damage. RESULTS: A good hemodynamic
      stability was observed. Recovery time was quick, related with brain damage and
      time of surgery. Incidence of postoperative nausea, vomiting and seizures was
      very low. Two cases of awareness were noted. CONCLUSIONS: 1982 neurosurgical
      operations were carried out in TIVA without major complications and side effects:
      the authors are therefore sure that TIVA can be considered the anesthetic
      technique "of choice" in neurosurgical patients.

PMID- 9567608
TI  - [Anesthesiologic management of susceptible children at risk for malignant
      hyperthermia].
AB  - In order to prevent malignant hyperthermia (MH) in children, the authors are
      currently using a perioperative anaesthetic protocol. In vitro contracture tests
      with halothane and caffein are performed in selected patients: those with
      previous signs suggestive of MH, but not severe enough for a definite diagnosis;
      those with susceptibility to MH in their relatives; those affected by myopathies
      or other disorders very frequently associated with MH. Even though CK should be
      considered an unreliable predictor of MH susceptibility, trigger agents are
      avoided in children with high and constant CK levels. However, prophylactic
      dantrolene is never employed. In this way, over the last decade no episodes of
      classic malignant hyperthermia in a large number of children submitted to
      anaesthesia (more than 50,000) have been observed.

PMID- 9567609
TI  - Electric nerve stimulation (ENS): 70 clinical cases of bi-block aided by an
      electric bipolar signal.
AB  - INTRODUCTION: The practice of local anaesthesia aided by ENS, among other things,
      is based on the use of available electric signals searching peripheral nerves.
      Most electric generators produce a square monopolar signal that is potentially
      dangerous because it exists a risk of hyperpolarization damage with neural
      lesions by galvanic effect. AIM: To inform about the use of a bipolar signal,
      different than the usual square monophasic signal. In theory a bipolar signal
      prevents the risk of hyperpolarization by lessening average intensity of current
      crossing the tissues. METHODS: Our experience is based on 70 clinical cases of bi
      block performed by searching the nerve by using an electric bipolar signal to
      locate a peripheral nerve. RESULTS: Local anaesthesia can be successfully
      performed by using bipolar electric signals not currently employed. In 2/70
      patients it was needed to perform surgery under general anesthesia. The rate of
      successful blocks was similar to the results of current literature. DISCUSSION
      AND CONCLUSIONS: Most authors search peripheral nerves by square monophasic
      signals. It arrives because it's widely believed that a square signal is
      advantageous because of high ratio di/dt (intensity/time). Today, it's not
      assessed in clinical practice that an electric signal is deeply modified in its
      parameters and its form by capacitive and resistive properties of the human body.

PMID- 9567610
TI  - [Intensity of treatment and severity of illness in the intensive care unit
      (ICU)].
AB  - OBJECTIVE: To investigate the relationship between Therapeutic Intervention
      Scoring System (TISS), length of ICU stay and severity of illness. DESIGN:
      Prospective study lasting 1 year. SETTING: Two 4-bed surgical-medical ICU.
      PATIENTS: All consecutively ICU admitted patients. METHODS: Every day TISS of
      each patient during the last 24 h was computed. Age, sex, type of admission, SAPS
      II and APACHE II, length of ICU stay and hospital outcome were recorded. Out of
      446 admissions, 14 were excluded since the ICU stay was < 16 h. Severity of
      illness was considered in 405 of the remaining 432; total TISS of readmitted
      patients resulted from all ICU admissions during the same hospital stay. RESULTS:
      Median TISS on day 1 was 24 (range 3-58, CI 95% 0.57) and median TISS +/- CI 95%
      during the first 10 ICU days ranged from 20 to 26. Spearman's correlation
      coefficient between TISS total and length of stay in ICU was 0.962. Total TISS
      increased with risk of hospital death predicted by both SAPS II and APACHE II.
      Total TISS of non surviving patients was significantly (p < 0.001) higher than
      that of the surviving up to probability of death of 20%. CONCLUSIONS: Intensity
      of treatment is essentially steady and total TISS is well related to length of
      ICU stay. Total TISS increases with increasing risk of hospital death predicted
      by SAPS II and APACHE II, but it is high especially in non surviving patients
      with low probability of hospital mortality at the admission.

PMID- 9567611
TI  - [Respiratory circuits and infections of the airway].
AB  - OBJECTIVE: To study the effects of ventilator circuit changes on the rate of
      airway infections and to investigate the relationship between the microorganisms
      responsible for circuit colonization and those responsible for infection. DESIGN:
      Prospective study, carried out in two different periods, of one year duration
      each. SETTING: General Intensive Care Units (ICUs) in a University Hospital.
      PATIENTS: Seventy-eight patients, requiring mechanical ventilation (VAM) for more
      than 5 days, were enrolled. They were divided into two groups: in the first
      (group I, n. 36, 1st period) the ventilator circuit was changed every 5 days; in
      the second (group II, n. 42, 2nd period) every 10 days. INTERVENTION: Ventilator
      circuit change every 5 or 10 days. Daily culvert and filling of cascade
      humidifiers with sterile irrigation water. Daily replacement of mount catheter.
      MEASUREMENTS: Qualitative cultures of tracheobronchial aspirate and of fluid from
      the humidifying cascades and the expiratory tubing traps. RESULTS: The two groups
      were similar. Pneumonia and tracheobronchitis were found in the 25% and 11% of
      patients of group I and in 26% and 12% of those of group II respectively. The VAM
      duration was 26.5 +/- 15 days in patients who developed airway infection, and
      12.9 +/- 11.6 days (p < 0.001) in patients who did not. The Gram+ organisms were
      predominant. An identical microorganism was found both in the tracheo-bronchial
      aspirate and in the circuit in 44 of 78 (56%) patients; no difference was found
      between infected (16 of 29) and non infected (28 of 49) patients. CONCLUSIONS:
      Changing the ventilator circuit every 10 days rather than every 5 days, does not
      increase the incidence of airway infections and result in considerable savings in
      the expenses of tubing and personnel time. The infection or colonization rates
      due to the same microorganisms are quite low and it seems not useful to make
      routine cultures of fluid from humidifying cascades and the expiratory tubing
      traps in order to characterize in time the microorganism that could be
      responsible of airway infections.

PMID- 9567612
TI  - [Case report of severe multiple trauma. Anesthesiologic techniques].
AB  - The modern anaesthetic devices have now put an end to the sixties-fashioned
      aphorism: "Closed circuit=open coffin". The currently renewed interest in the
      recirculation systems is justified by the following reasons: economic benefit;
      environmental advantages; clinical features, such as: 1) better humidification of
      gases; 2) better preservation of warmth; 3) monitoring of O2 consume; 4) gas
      analysis on each respiratory act. This allows the use of fresh gases at low flow
      without the risk of hypoxia or overdosage in patients and it guarantees for safe
      anaesthesia. The following clinical case clearly shows the application of the
      above mentioned principles. An extremely serious case of head, chest and
      abdominal multiple trauma, personally observed, is described. The so called
      technics "partial rebreathing" was adopted thanks to the availability of a device
      which permits a punctual monitoring of SAO2, ETCO2, FI and FET, FLO2, VM, VT,
      VEmin, % of N2O, invasive SAP and body temperature. These are very important
      parameters for a safe anaesthesia and in conditions like those of the above
      described clinical case.

PMID- 9567613
TI  - [Osteo-conductive materials: animal experiments and instrumental analysis II].
AB  - BACKGROUND: In daily dental surgery practice, when it is not possible to obtain
      enough autogenous bone graft to fill bone defects, bone substitutes can be useful
      for bone regeneration. MATERIALS AND METHODS: After a preliminary microscopic
      examination of histologic samples obtained from semithin sections of the tibias
      of rats showing no major differences in the results both for the single material
      and implant time, further studies on five different osteoconductive materials
      used in oral clinical practice were carried out with microradiography, SEM and X
      ray microanalysis. In experimental animals (rats) bone defects 3 mm large were
      surgically induced in both tibias: one of the defects was filled by bone
      substitutes and on the other side the bone defect healed naturally. RESULTS AND
      CONCLUSIONS: The findings obtained were studied in depth, and allowed to conclude
      that the materials tested are suitable for the purpose for which they are
      marketed. Non-demineralized bovine bone showed the best results with a high
      degree of osteointegration. However, the results also show that not all the
      materials tested offer healing advantages over controls.

PMID- 9567614
TI  - [Study of compression resistance of conventional or passive post and core
      reconstructed roots].
AB  - BACKGROUND: The object of this study is to estimate if the reconstructed roots
      with passive post and core have a greater resistance to compression in relation
      to reconstructed roots with traditional post and core. MATERIALS AND METHODS:
      Experimental situations have been reproduced as close as possible to real
      clinical situations simulating the cervical edge of the crown with a supporting
      cervical ring. A comparative analysis of the resistance to compression has been
      carried out using three groups of roots: the first group constructed from
      reconstructed roots with traditional post and core; the second group of
      reconstructed roots with passive post and core; the third group of roots were not
      reconstructed. RESULTS: Our results have shown that if the root reconstruction
      includes a metallic support ring that goes beyond the root plate by at least 1 mm
      there is no difference in the resistance to compression of statistical
      significance between reconstructed roots with passive post and core and
      reconstructed roots with traditional post and core. It turns out instead that
      there is a significant increase in resistance to compression of the reconstructed
      roots (because of the presence of the cervical support ring) in respect of the
      third group of unreconstructed roots.

PMID- 9567615
TI  - [Treatment of dentin sensitivity with stannous fluoride gel. Electron microscopic
      study and evaluation of dentin permeability].
AB  - Dentine hypersensitivity still represent a major clinical problem only partially
      solved. The presence of exposed opened dentinal tubules has been demonstrated
      increase the dentine permeability and it is the responsible for pain and
      sensitivity. Stannous fluoride solution has been recently proposed to reduce
      dentine hypersensitivity. The aim of the present study was to evaluate the
      dentinal permeability of a new stannous fluoride gel proposed for the therapy of
      dentine hypersensitivity. Human extracted teeth have been used and mounted and
      connected with a hydraulic pressure apparatus working at 1 psi (70 cm of water
      pressure). It was calculated the permeability of untreated smear layer, treated
      smear layer (after gel application) and after acidic treatment. It was observed
      that gel treatment was able to reduce dentine permeability. Scanning electron
      microscopy demonstrated the presence of a homogeneous smear layer after treatment
      with gel. This in vitro study confirms that stannous fluoride treatment has the
      capacity to modify dentine permeability of sensitive dentine.

PMID- 9567616
TI  - [A peculiar form of anemia in patients operated on for cancer of the oral
      cavity].
AB  - The authors related about a peculiar form of anemia found in some patients
      operated on oral cancer; these patients had an almost normal hematic situation
      before their operation. 63 patients, operated in the course of a year for oral
      cancer, have been studied by the authors; they have found in 14 cases (22.2%) a
      light anemia which regressed after a self blood transfusion, during the first
      week after the operation; in other 8 cases (12.7%) the anemia, which was more
      serious, persisted beyond the 7th day after the operation. Those 8 patients,
      suffering from more serious and persistent anemia, were treated from 7th to 21st
      day after the operation with iron, vitamin B12 and folic acid without any
      improvement. The hematic situation improved about 10 days after the end of
      treatment, probably as a result of spontaneous renewal of medullar haemopoietic
      activity. This anemia, is characterized by normochromia, normocytosis, reduced
      response of reticulocytes, sideropenia and hyperferritinaemia. The authors think
      that the pathogenesis of anemia after operation in neoplastic patients is caused
      by medullary insufficiency existing before the operation, connected with reduced
      erythropoietin production and emphasized by an operation that sometimes cause
      bleeding. Consequently the authors hypothesis the use of erythropoietin in the
      therapy of most severe anemia in neoplastic operated patients.

PMID- 9567617
TI  - [p53 mutation and chemoresistance in oral-maxillofacial squamous cell carcinoma.
      Role of p53 in the cell cycle control and in the modulating action of
      chemotherapeutic agents].
AB  - p53 is a "tumor suppressor gene" with a basic function in the cellular cycle
      control and subsequently in the induction of the neoplastic process. p53 found
      changed in the majority of malignant human tumors. In the oral and maxillofacial
      cancers p53 mutations varies from 4% to 60% of the cases. Researches in vitro in
      tumors of the colon-rectum, breast, lung, ovary, testicle, bladder and in
      leukaemia, show a correlation between p53 overexpression (mutation) and
      resistance to the anti-tumor agents. The functional connection between the p53
      and the chemotherapic drugs action which cause a direct DNA damage, is the
      apoptosis, a physiologic mechanism activated by p53 for regulating cell growth
      but also indispensable for the cytotoxic effects (apoptosis is an irreversible
      process culminating in cell death). Loss of the p53 activity (mutation) in the
      tumoral cells determines non-activation of the apoptosis and the drug resistance.
      These results have led to early clinical applications. In the breast cancers the
      p53 is already utilized as chemoresistance marker, directing the therapy, if
      changed to alternative drugs (Taxolo) which have a p53-independent action. Even
      into cell lung cancers a retroviral vector containing the wild-type p53 gene was
      produced to mediate transfer of wild-type p53, noting tumor regression. In oral
      and maxillofacial tumors surgery is elective. It is emphasized that, in advanced
      cancers, it is included in multimode protocols where the neoadjuvant chemotherapy
      has an important clinical function, with precise indications. The possibility to
      determine previously the p53 "status" in the cancer cells by genetic study, may
      give a specific factor of screening, indicative of the tumor chemoresponse,
      together with other well-known prognostic factors, with advantage for the
      therapeutic programming and especially for the known surgical treatment.

PMID- 9567618
TI  - [Pathology of taste: knowledge and prospectives].
AB  - Taste anomalies have not been systematically investigated till recently in Italy.
      The influence of the taste on the choice of the foods, on the nutrition and on
      the same psycho-physic human mindedness has largely been demonstrated. In this
      study, taste anomalies associated with various pathologic conditions (nervous,
      endocrine, metabolic, infectious, immunological, carential or neoplastic
      disorders) are reported, as well as those produced by drugs, or surgical
      interventions. The type and the degree of taste anomalies associated to
      immunological diseases, allogeneic bone marrow transplantation and AL amyloidosis
      are particularly described.

PMID- 9567619
TI  - [The Melnick-Needless syndrome (osteodysplasia). Report of a clinical case].
AB  - The case of a girl with Melnick-Needles syndrome is reported. The face is
      characterized by prominent sopraorbital ridges, prominent eyes, full cheeks,
      large pinna, marked micrognathia, strabism, blue sclerae. Lateral and postero
      anterior cephalometric measurements are presented and odontostomatologic features
      of the syndrome are described.

PMID- 9567620
TI  - [Rokitamycin in odontostomatology. Controlled study of doses].
AB  - BACKGROUND: Rokitamycin is a semisynthetic macrolide with a lactonic ring with 16
      atoms, showing anti-bacterial action at concentrations near to MIC. A controlled
      clinical study is carried out, in parallel groups, whose aim was to assess the
      therapeutic action and safety of two dosage schemes of rokitamycin, in the short
      term treatment (5 days) of acute infective processes of odontostomatological
      origin. METHODS: Twenty patients (14 males, 6 females) were recruited for the
      trial, suffering from alveolitis, abscess, phlegmon, sialadenitis and suppurating
      cysts. The patients were divided in a randomized fashion into two groups: 10
      patients were treated orally with 800 mg/day and 10 with 1200 mg/day. Rokitamycin
      was supplied in 400 mg tablets. RESULTS: The 5 days of treatment with rokitamycin
      determined the complete resolution of the infective process, with eradication of
      the germs originally isolated, all belonging to the Streptococcus genus. Clinical
      efficacy was evident by the third day of treatment, with a prompt improvement of
      symptoms (functional limitation, pain, tumefaction) and the return of body
      temperature to within normal limits, in a totally superimposable fashion between
      the two groups. Safety was excellent with both doses, with no side effects
      observed. CONCLUSIONS: The results of the study show that treatment with
      rokitamycin in the short term, at the usual dosage of 800 mg/day, is a valid
      therapeutic scheme in infective processes in odontostomatology.

PMID- 9567621
TI  - [Tuberculosis, a health priority problem in 1997 too].

PMID- 9567622
TI  - [The descriptive epidemiological aspects of bronchopulmonary neoplasms in Dolj
      County].
AB  - This study represents a descriptive epidemiologic analysis of the morbidity and
      mortality incidence by lung cancer in Dolj. The usual processing of the
      registered values in primary evidences (report of the new cases to 100,000
      residents) is in accordance with the literature about the variation of the
      incidence depending on residential environment and sex greater values in urban
      environment and at man, beginning from the fifth decade of life. The
      epidemiologic analysis by indirect standardisation of the mortality and the
      morbidity emphasizes in Dolj higher incidence up to the media of the Dolj,
      specially in the rural environment, aspects that suggest the intervention of the
      environmental factors and behaviour factors in the etiology of the lung cancer.

PMID- 9567623
TI  - [The results of the chemotherapy of a patient cohort with pulmonary tuberculosis
      followed-up for a 3-year period].
AB  - In 1992, in the fourth district of Bucharest 184 news adult patients with
      pulmonary tuberculosis were registered, and they received specific chemotherapy.
      The initial sputum bacteriological examination was M+C+ in 63.1% of these
      patients, M-C+ in 21.7% and M-C- in 15.2%. After three years of surveillance the
      results of the treatment were evaluated. 27 patients were excluded from the
      initial group, because they failed to be controlled. The final results were
      influenced by the sex and the initial bacteriological examination of sputum: the
      persistent negativation of sputum was obtained in 96.2% of the women, and only in
      89.5% of men; depending on the initial bacteriological sputum examination, 100%
      of the M-C+ cases were negated, but only 86.4% of the M+C+ group.

PMID- 9567624
TI  - [The anatomico-radio-clinical forms of onset in pulmonary tuberculosis].
AB  - The aim of the study was to analyze the frequency of various radio-clinical forms
      of onset in newly discovered TB cases, in the area of the Sibiu dispensary on a
      period of 3 years (1992-1994). In the 327 cases included in the study, there was
      an equal sex ratio, with a symptomatic period of at least 3 months before the
      diagnosis. There was an increased percentage of unilateral cavitary forms, with
      an equal distribution in city and rural area. The severe forms were more frequent
      in villages and in male patients. The young patients (under 24) had mostly
      cavitary forms. The cavitary forms were more frequently associated with other
      illnesses than the caseous forms.

PMID- 9567625
TI  - [Secondary active-evolutive cavitary pulmonary tuberculosis of the apicodorsal
      segment of the left upper lobe associated with bronchial tuberculosis and
      bronchial geotrichosis].
AB  - A case of active pulmonary secondary tuberculosis associated with bronchial
      tuberculosis and bronchial geotrichosis is presented. This association is
      infrequent. Favoring factors: local and general immunodepression (recurrent
      infection with pyogenic germs, rubella, neutropenia, aggressive antibiotherapy,
      iron deficiency). The diagnosis was based mainly on the bacteriological sputum
      examination for bK (smear and culture) and the mycologic examination (smear and
      culture) of the bronchial aspiration, identifying Geotrichum candidum. The
      treatment consisted of antituberculous and antimycotic drugs, bronchodilators,
      bronchial aspirations and local endoscopic administration of antimycotic drugs.

PMID- 9567626
TI  - [Diffuse interstitial pneumopathy after the treatment with gold salts of a
      patient with rheumatoid polyarthritis].
AB  - We present the case of a male patient with sero-negative rheumatoid arthritis,
      treated with gold salts, admitted for clinical symptoms and chest X-ray
      alterations suggesting an interstitial lung disease. This was confirmed by
      complex lung function tests and fiber bronchoscopy with broncho-alveolar lavage.
      Considerations are made about the etiology of interstitial lung disease
      (pulmonary determination of the rheumatoid arthritis or secondary to the gold
      salts therapy), about the treatment and long-term prognosis, and about the good
      clinical, functional and radiological evolution under treatment.

PMID- 9567627
TI  - [Criteria for the preoperative evaluation of the risk of postoperative
      complications in pulmonary resections].

PMID- 9567628
TI  - [Video thoracoscopy--the boundary between minimally invasive surgery and invasive
      investigation].

PMID- 9567629
TI  - [Post-tuberculous respiratory syndromes (PTRS)].

PMID- 9567630
TI  - [A prospective study on the extent and views of smoking in a group of 13- and 14
      year-old schoolchildren].

PMID- 9567631
TI  - [Obstetric analgesia-anesthesia: state of the art].

PMID- 9567632
TI  - [Obstetrical anesthesia in 15 women with myasthenia gravis].
AB  - OBJECTIVES: To report our experience in managing anesthesia during obstetric
      delivery of women with myasthenia gravis (MG) and to review the anesthetic
      technique of choice for vaginal or cesarean delivery in such cases. PATIENTS AND
      METHODS: Fifteen pregnancies in 12 patients were recorded between 1980 and 1996;
      14 cases were documented. Disease course during pregnancy, delivery and
      postpartum, the course of pregnancy, the presence of severe neonatal myasthenia
      and anesthetic treatment during vaginal or cesarean delivery were analyzed.
      RESULTS: Improvement in MG was observed in 6 cases. No change was seen in 4
      patients and 3 worsened. In one woman generalized MG debuted 15 days after
      delivery. Two neonates were premature and a third suffered severe neonatal
      myasthenia. Six vaginal deliveries were aided by forceps; 8 deliveries were by
      cesarean and 1 fetus was aborted. Lumbar epidural anesthesia was employed in
      73.33% (5 vaginal deliveries and 6 cesareans) and general anesthesia in 26.66% (1
      abortion, 1 vaginal delivery and 2 cesareans). CONCLUSIONS: Continuous lumbar
      epidural anesthesia is the technique of choice for vaginal as well as cesarean
      deliveries. The combination of opioids and local anesthetics is considered
      particularly beneficial for patients, as it allows the motor blockade to be
      decreased. General anesthesia is only indicated when there is bulbar involvement.
      Short-acting non depolarizing agents, among them atracurium Besilate, are the
      muscle relaxants of choice. Succinylcholine is contraindicated. Thanks to current
      optimization of anesthetic and recovery techniques and administration of non
      depolarizing muscle relaxants with neuromuscular monitoring, the prognosis for
      pregnant MG patients has improved considerably.

PMID- 9567633
TI  - [Comparison of lidocaine and urapidil for prevention of hemodynamic response to
      tracheal intubation in patients in general good health].
AB  - OBJECTIVE: To compare the efficacy of endovenous administration of 0.5 mg/kg-1 of
      urapidil to 1 mg/kg-1 of lidocaine for attenuating hemodynamic response to
      laryngoscopy and tracheal intubation. PATIENTS AND METHODS: Study of 40 ASA I and
      II patients with normal blood pressure undergoing elective surgery under general
      anesthesia with orotracheal intubation. The patients were randomly assigned to
      two groups to receive either 0.5 mg/kg-1 of urapidil or 1 mg/kg-1 five minutes
      before anesthetic induction. Anesthesia was provided with 0.04 mg/kg-1 of
      midazolam, 2 micrograms/kg-1 of fentanyl, 2 mg/kg-1 of propofol, 0.1 mg/kg-1 of
      vecuronium before proceeding to orotracheal intubation, after electromyographic
      determination of neuromuscular response with T1 less than 5%, and laryngoscopy.
      Heart rate, systolic, diastolic and mean pressures, and the product of heart rate
      and mean arterial pressure (HR x MAP) were recorded at the following times:
      baseline (before administering either lidocaine or urapidil), after induction,
      after laryngoscopy and intubation, and 3 minutes and 5 minutes after intubation.
      RESULTS: ASA classification, age, sex and weight were similar in the two groups.
      Heart rate immediately after intubation, and after 3 and 5 minutes was
      significantly lower in the lidocaine group. Likewise HR x MAP immediately after
      intubation and 3 minutes later was significantly lower in the patients who
      received lidocaine. CONCLUSIONS: In healthy ASA I and II patients with normal
      blood pressure, a dose of 1 mg/kg-1 of lidocaine provided better protection
      against the hemodynamic response to laryngoscopy and tracheal intubation than
      does 0.5 mg/kg-1 of urapidil.

PMID- 9567634
TI  - [Perioperative renal protection: physiopathological basis of acute renal
      insufficiency and prophylactic methods].

PMID- 9567635
TI  - [Early pressure in pneumocephalus: an perioperative complication in
      neuroanesthesia].
AB  - We report two cases of early-onset pressure pneumocephalus, one occurring during
      supratentorial brain surgery (craniopharyngioma) which was diagnosed at the end
      of the anesthetic period upon appearance of comatose status leading to the
      suspicion of surgical complication in the form of a hematoma. The second case of
      pneumocephalus was detected after posterior fossa surgery performed with the
      patient in the sitting position. We review the significance of our anesthetic
      management on the prevention of tension pneumocephalus, and discuss diagnostic
      and therapeutic measures available for use in the Postoperative Intensive Care
      Recovery Unit.

PMID- 9567636
TI  - [Pressure pneumocephalus after posterior fossa surgery in the sitting position].
AB  - Pneumocephalus occurs commonly soon after intracranial surgery. When it presents
      as a significant increase in intracranial pressure it is called pressure
      pneumocephalus, a severe, life-threatening complication of neurosurgery that
      requires immediate treatment. Tension pneumocephalus must be suspected in
      patients unexpectedly fail to awaken at the end of surgery or who present
      progressive neurological deterioration after posterior fossa surgery. Diagnosis
      is by computerized axial thomography of the brain. Treatment is simple,
      consisting of promptly releasing the pressurized gas by trephination to save the
      patient's life or prevent severe neurological sequelae. We report two cases of
      pressure pneumocephalus that illustrate several risk factors: sitting position
      during surgery, preoperative hydrocephaly, surgical opening of the fourth
      ventricular and the presence of cerebrospinal shunt during surgery.

PMID- 9567637
TI  - [Acute pulmonary edema during delivery of a pregnancy with HELLP syndrome].

PMID- 9567638
TI  - [Anesthesiologic implications for epidermolysis bullosa. Presentation of a case].

PMID- 9567639
TI  - [Propofol and laryngeal mask in magnetic resonance].

PMID- 9567640
TI  - [Endoscopic biliary prosthesis in the treatment of malignant obstructive
      jaundice].

PMID- 9567641
TI  - Endoscopic stenting in the management of malignant biliary obstruction.
AB  - A relevant percentage of patients with malignant biliary obstruction are not
      candidates for surgery when the diagnosis is made. Endoscopically placed biliary
      stents have shown their efficacy in the palliative management of these patients
      although they do not seem to increase their survival. We report on a
      retrospective analysis of 37 patients with malignant biliary obstruction treated
      with endoscopic biliary stents. The distal third (62%) of the main life duct was
      the most frequent common location for the obstruction, and pancreatic cancer was
      the most frequent cause of obstruction (64%). Twenty three plastic (13-7F and 10
      10F) and 14 metallic stents were placed initially. Forty four percent of the
      plastic stents (all of them 7F, none 10F) were removed after 39 days against 30%
      of the metallic stents after a mean period of 60 days. Global survival was 153
      days (110 in the plastic stents' group versus 195 in the metallic one, p: NS). We
      could only make a complete follow up in 52% of the patients. CONCLUSIONS:
      endoprotheses are a good palliative treatment for malignant biliary obstruction.
      When plastic stents are used they should have a wide calibre (10F or greater).
      Metallic stents result in an increase of survival time without statistical
      significance.

PMID- 9567642
TI  - Can digital examination substitute anorectal manometry for the evaluation of anal
      canal pressures?
AB  - INTRODUCTION: Anorectal manometry provides objective information on the sphincter
      function of the anal canal. However, in many centers sphincter function is
      evaluated by digital examination, due to the unavailability of manometry.
      OBJECTIVE: A study is made to correlate the sensitivity and specificity of a
      quantitative digital examination in the analysis of sphincter tone with the
      pressures recorded by manometry, and to examine the capacity of both techniques
      to discriminate continent subjects and incontinent patients. PATIENTS AND
      METHODS: A total of 191 patients were divided into three groups: control (C),
      obstructive defecation (OD) and fecal incontinence (FI). Subjective quantitative
      digital evaluation of anal tone was performed on a scale of 0 to 5 points at
      rest, and 0 to 10 points at squeeze. A correlation analysis was performed, and
      the sensitivity and specificity of each fecal incontinence diagnostic test was
      determined. RESULTS: Digital examination found rectal tone to be diminished in
      elderly patients. A significant correlation was established between the digital
      and manometric tone readings, both at rest and at squeeze. Both techniques showed
      a low anal sphincter pressure in the FI group versus the C and OD groups.
      Differences in tone were recorded between the C and OD groups with manometry, but
      not with digital examination. The latter was in turn found to be more sensitive
      but less specific than manometry in differentiating between fecal continence and
      incontinence. CONCLUSIONS: Although digital examination does not substitute
      anorectal manometry, a good correlation exists between the two techniques. In
      this sense, digital examination may afford an approximate clinical evaluation of
      some fecal continence mechanisms in those centers where manometry is not
      available.

PMID- 9567643
TI  - Hemodynamic monitoring in a model of shock induced by intestinal reperfusion in
      the rat.
AB  - OBJECTIVE: An experimental model to monitor hemodynamics during intestinal
      reperfusion syndrome is presented. EXPERIMENTAL DESIGN: A) Three groups of rats
      were monitored during four hours: 1) CONTROL: sham operated, 2) Ischemic:
      clamping the superior mesenteric artery for 60' and 3) Saline: adding 2 ml of
      saline during the last 15' minutes of ischemia. Blood mean pressure, heart rate,
      breath rate and diuresis are monitored, while mortality is assessed 48 hours
      later, B) Blood gases, haematimetry and electrolytes were assessed both in
      control animals and in rats subjected to intestinal ischemia and reperfusion (at
      the beginning and concluding the ischemic period, and 5', 60' and 180' following
      reperfusion). RESULTS: Mortality rate was 0% for control animals, while 83% for
      both ischemic-reperfused groups (p < 0.01). Hemodynamic parameters remained
      stable during intestinal ischemia. Starting reperfusion, blood pressure and
      diuresis dropped sharply, while heart and breath rates showed a steady increase.
      The other parameters assessed also remained constant during ischemia. However,
      during reperfusion acidosis progressed (pH = 7.15, p < 0.01; HCO3 = 8, p < 0.01),
      hyperkalaemia appeared (6 mEq/l, p < 0.01), and haematocrit rose (56%, p < 0.01).
      CONCLUSION: This experimental model is easy to establish, allows an appropriate
      hemodynamic monitoring of shock during intestinal reperfusion syndrome, and seems
      appropriate for considering the impact of drug intervention.

PMID- 9567644
TI  - [A patient with five synchronous adenocarcinomas of the colon].

PMID- 9567645
TI  - [Small intestine obstruction caused by a splenic flexure volvulus of the colon].

PMID- 9567646
TI  - [Gastric necrosis associated with intestinal obstruction].

PMID- 9567647
TI  - [Reduction of automobile traffic: urgent health promotion policy].
AB  - During the last few decades, traffic injuries have become one of the leading
      causes of death and disability in the world. In urban areas, traffic congestion,
      noise, and emissions from motor vehicles produce subjective disturbances and
      detectable pathological effects. More than one billion people are exposed to
      harmful levels of environmental pollution. Because its combustion engine
      generates carbon dioxide (CO2), the automobile is one of the chief sources of the
      gases that are causing the greenhouse effect. The latter has already caused a
      rise in the average ambient temperature, and over the next decades it will
      predictable cause significant climatic changes whose consequences, though
      uncertain, are likely to be harmful and possibly catastrophic. Aside from the
      greenhouse effect, the relentless growth of parking zones, traffic, and the
      roadway infrastructure in urban and rural areas is currently one of the leading
      causes of environmental degradation. Urban development, which is nearly always
      "planned" around traffic instead of people, leads to a significant deterioration
      in the quality of life, while it also destroys the social fabric. Unlike the
      private automobile, public transportation, bicycles, and walking help reduce
      pollution, congestion, and traffic volume, as well as the morbidity and mortality
      resulting from injuries and ailments related to pollution. Non-automobile
      transportation also encourages physical activity--with its positive effect on
      general health--and helps reduce the greenhouse effect. The drop in traffic
      volume and the increased use of alternate means of transportation are thus an
      integrated health promotion policy which should become an inherent part of the
      movement for the promotion of healthy cities and of transportation policies and
      economic policy in general.

PMID- 9567649
TI  - [Chagas disease in the central region of Honduras: knowledge, beliefs, and
      practices].
AB  - From November to December 1991 and in March 1993 a survey was conducted in 17
      rural communities located in Central Honduras. The communities belonged to two
      areas where Chagas' disease is endemic. In one of them, disease control
      activities had been conducted. A total of 849 adults, one in each of an equal
      number of households, was interviewed. The objective of the survey was to
      investigate and compare in both locations knowledge about Chagas' disease and its
      routes of transmission, measures aimed at avoiding the presence of triatomines
      within households, beliefs surrounding the vector and its control, and the
      population's sources of information about the disease. A 23-item questionnaire
      was tested and precoded. Almost 100% of the subjects who were surveyed were able
      to identify the vector and to describe its habits, but only 30.1% knew that
      Triatoma is the vector for the disease and only about 6% associated it with a
      chronic heart condition. Around 47.9% of survey subjects indicated that
      eliminating triatomines from households is a personal responsibility, although
      78% identified as the control measure the institutional application of
      insecticides. Personal contact between a health worker and community members was
      the chief source of information for those who mentioned having heard of Chagas'
      disease (41.0%). These results suggest that health education should be included
      as a component in the planification of control programs. The role played by
      triatomines in disease transmission should be emphasized, as well as the
      importance of carrying out household improvements, with community participation,
      as an effective and sustainable measure. To achieve greater impact, this
      component should be developed through interpersonal communication channels.

PMID- 9567650
TI  - [Distribution of body mass indices of a Brazilian population under 25 years of
      age].
AB  - This paper presents the percentage distribution of the body mass index of the
      Brazilian population from birth to age 25, based on a national survey conducted
      in 1989. Survey data show that body mass index decreases from birth until around
      6 years of age, reaching a plateau at 8 years and progressively increasing until
      the age of 19 or 20 years for females and 20 or 21 for males. The survey also
      revealed that after the age of 12 females present a greater body mass index than
      males, as well as a larger range of percentile values (from 3 to 97). A
      comparison with data from other countries showed that the body mass index profile
      in Brazil is similar to that observed in France, Great Britain, and the United
      States. Before the age of 6, Brazilian youngsters have a mean body mass index
      that resembles that of North American children, and a lower one thereafter. A
      comparison between the median body mass index of Brazilian and British youngsters
      revealed consistently lower values among Brazilian females. When compared to that
      of France, Brazil's male population has a systematically lower body mass index
      after the age of 8. It is suggested that the data presented in our study be used
      only for comparing groups of individuals and studies, and not for screening or
      clinical monitoring, due to the great variability in growth patterns during
      adolescence.

PMID- 9567651
TI  - [Detection of IgM against the dengue++ virus in whole blood absorbed on filter
      paper].
AB  - This paper presents a standardized procedure for the detection of IgM antibodies
      to dengue virus in blood samples taken from filter paper. The samples were
      obtained from 118 patients, of whom 91 had been clinically diagnosed with dengue
      and 27 with a viral infection unrelated to that disease. The first group of
      patients came from Costa Rica and Nicaragua and the second group from Cuba. All
      the samples were tested for IgM antibody against dengue virus by means of a
      capture enzyme immunoassay (EIA). Analysis of the results for patients from all
      three countries together yielded a sensitivity of 98.1% and a specificity of
      98.5% for the test done on whole blood on filter paper stored at 4 degrees C;
      agreement between the results of that test and those of the EIA using serum
      samples was 96%. In a comparison of the results obtained with three samples from
      the same patient--whole blood on filter paper stored at room temperature, the
      same type of sample stored at 4 degrees C, and serum--the agreement was 86%. This
      study demonstrates the high diagnostic sensitivity and specificity achieved when
      whole blood absorbed on filter paper is processed in the manner described in
      detail in the article. The authors recommend the use of this method in the dengue
      surveillance programs in the Region.

PMID- 9567654
TI  - [Perception of the quality of care in the health services in Mexico. perspective
      of the users].
AB  - OBJECTIVE: To describe the quality of health services as perceived by users in
      Mexico, as well as an analysis of predisposing and enabling factors to the use of
      these services. MATERIAL AND METHODS: Data were selected from the National Health
      Survey II of 1994. The survey contains information from 3324 ambulatory health
      service users who sought care in the two week period previous to the survey.
      RESULTS: 81.2% of users perceived the quality as good and 18.8% thought it was
      poor. The main reasons for good quality of care were: personal attention (23.3%)
      improvement of the health problem (11.9%). For poor quality of care, the main
      reasons were: long waiting time (23.7%) and poor clinical examination (11.7%)
      Social security health service users perceived 2.6 times more frequently quality
      of attention as poor, than those who consulted private health services. Quality
      is represented by the aspects of the attention process (44.8% 9, its results
      (21.3%), the structure (18.0%) and accessibility (15.7%) The main reasons for not
      returning to the same health service center were: deficient attention (18.2%) and
      long waiting times (11.8%). CONCLUSIONS: The perspective of the population should
      be studied further and actions for the continuous improvement of the quality of
      health care should be implemented.

PMID- 9567655
TI  - [Prescriptions, access, and expenses on drugs among users of health services in
      Mexico].
AB  - OBJECTIVE: To analyze the medical prescription, drug access and drug expenditure
      by patients based on the National Health Survey in Mexico, 1994. MATERIAL AND
      METHODS: A descriptive analysis of drug access and expenditure was undertaken and
      predictive factors for medical prescription were identified by logistic
      regression for 3,324 patients. RESULTS: 78% of the patients received drug
      prescriptions. 92% of the Social Security patients and 35% of the Ministry of
      Health patients received drugs free of charge (p = 0.000). The region with the
      highest poverty index received the least amount of drugs free of charge.
      Regarding drug expenditure of patients who purchased drugs, median expenditure
      was 40.00 pesos (12.50 USD). Private health service patients spent significantly
      more than public health service patients. CONCLUSIONS: Drug access and drug
      expenditure are linked to socioeconomic factors and to the institutions attended
      by patients. The Mexican health system faces, among others, the challenge of
      increasing the equity of access to medical drugs.

PMID- 9567656
TI  - [Concordance of the clinical and autoptic pathological diagnosis].
AB  - OBJECTIVE: To determine the degree of concordance between clinical and autopsy
      diagnosis. MATERIAL AND METHODS: The records of 67 autopsies and clinical files
      of children and adults, comprising the years 1995 to 1996, from a third level
      hospital in the State of Veracruz, Mexico, were revised. The concordance score
      was calculated with the statistical kappa. RESULTS: In general, the rate of
      autopsy was 10.5%, with higher frequency for children (17.5%). In children, 59%
      of clinical diagnoses revealed mistakes and in adults, 57%. The degree of
      agreement in the underlying cause ante and postmortem was 26% in children and 41%
      in adults. CONCLUSIONS: The high rate of diagnostic error and low concordance
      score between clinical and autopsy diagnosis strongly suggests that, in spite of
      increased availability of modern diagnostic techniques, the necessity of
      postmortem studies to control the level of medical practice is evident.

PMID- 9567657
TI  - [Perspectives for the development of vaccines and immunotherapy against cervico
      uterine cancer].
AB  - Cervical cancer represents a severe public health problem and has been associated
      to the presence of human papillomavirus. Strategies are presently being tested
      which target the virus to attempt to control disease progress. Studies on the
      humoral and cell-mediated immunity of the papillomavirus infection have been
      useful in the development of a vaccine. Synthetic virus-like particles have been
      validated as vaccine against several animal papillomaviruses and used to map the
      seroepidemiology of the human papillomavirus infection, and define neutralizing
      antibodies. Induction of cell-mediated immunity to HPV early proteins is bound to
      become a therapeutic approach to HPV infections. Recent advances have centered on
      directing the immune response to prevent infection, to virus-infected cells and
      to virally transformed cells, with favourable results.

PMID- 9567658
TI  - [Smoking in health personnel: study in a hospital unit].
AB  - OBJECTIVE: To analyze the characteristics of smoking among health personnel,
      considered to be of particular importance for their strategic influence on the
      population. MATERIAL AND METHODS: A short survey was designed and applied in
      April 1997 to health personnel in one Mexico City hospital. Information and
      personal view on tobacco addiction was taken from smokers and non-smokers and
      analyzed by sex, age, region, function, shift, etc. RESULTS: Prevalence among
      administrative and medical personnel was high. CONCLUSIONS: The high smoking
      prevalence among health personnel should be carefully considered since it is
      opposed to medical principles on formation, activity and environment.

PMID- 9567659
TI  - [Child abuse: a world problem].
AB  - Several problems are encountered in the study of child abuse: ignorance of its
      real proportions, deep cultural and historical roots, diversity of opinion as to
      its definition and classification and, finally, very diverse considerations on
      its repercussions and therapeutic management. The present study approaches child
      abuse from its historical precedents, its classifications, definitions and
      epidemiology. In addition, repercussions are reviewed, and treatment alternatives
      considered which are held as fundamental to confront this alarmingly increasing
      phenomenon. It is important to unify criteria as to the definition and
      classification of scientific information surrounding demographic data which, in
      the end, will situate the problem, the progress related to its causes, diagnosis,
      preventive measures and treatment. It is extremely important to prevent child
      abuse by all possible means, since this harm is reflected in the adult life of
      the child. Various classifications are considered, as well as characteristics of
      the abuser and of the abused.

PMID- 9567660
TI  - [Conceptual and methodologic bases of the National Health Survey II, Mexico,
      1994. Conceptual Coordinating and Designing Group of ENSA-II].
AB  - The conceptual and methodological basis of the National Health Survey II (NHS-II)
      are described and recent advances in multidisciplinary public health research in
      Mexico, both conceptual and methodological, are synthesized. The design of the
      NHS-II concentrated on the study of the access, quality of care and health
      attention expenses in ambulatory and hospitalization services. Details on the
      conceptual framework related with the analysis and processing of data are also
      included. Five geographic regions were covered; 12,615 households at national
      level were visited and information on 61,524 individuals was gathered. The
      overall response rate was 96.7% both for households and for identified health
      service users. The general conclusion emphasises the need to incorporate the
      population perspective to the planning and allocation of health resources.

PMID- 9567662
TI  - [Statistics of hospital discharges of the Department of Health, 1996].

PMID- 9567663
TI  - Rethinking the relationship between ethnicity and mental health: the British
      Fourth National Survey of Ethnic Minorities.

PMID- 9567664
TI  - The measurement of culture shock.
AB  - This paper describes the development and evaluation of a new questionnaire to
      measure culture shock. The population was young British volunteers working in a
      variety of cultural settings overseas (N = 380). Core culture shock items were
      derived from a consensus statement from the literature on culture shock.
      Additional items were obtained from an analysis of reports by previous
      volunteers. Internal consistency of items, as determined by correlation
      coefficients and factor analysis, was satisfactory; this also lends some
      empirical support to the concept of culture shock. External criterion validity
      was established by reference to the country of destination and correlation with a
      measure of cultural distance. A 12-item questionnaire to measure culture shock is
      offered for further use and evaluation.

PMID- 9567665
TI  - Risk factors for suicide in Caucasians and in African-Americans: a matched case
      control study.
AB  - It is known that suicide rates for Caucasians are higher than those for African
      Americans. However, there has been little research examining whether risk factors
      associated with suicide differ by race, when the effects of age, gender, and
      educational-occupational status are taken into account. A matched case-control
      study was constructed from the 1986 National Mortality Followback Survey to
      address such concerns. Cases included all individuals aged between 25 and 64
      years dying from suicide. Controls were those who died of natural causes, who
      were frequency matched to cases by age and gender. The study results for
      Caucasians indicate that those who had at least a high school education were more
      likely to commit suicide [odds ratio (OR) = 1.91; 95% confidence interval (CI) =
      1.37-2.67] than those who had less than a high school education; those who were
      heavy drinkers were more likely to commit suicide (OR = 1.64; 95% CI = 1.16-2.33)
      than those who were light or moderate drinkers; those who lived alone were more
      likely to commit suicide (OR = 1.72; 95% CI = 1.28-2.30) than those who lived
      with others, those who had blue-collar occupations were more likely to commit
      suicide (OR = 1.79; 95% CI = 1.33-2.42) than those who had white-collar
      occupations, and those who had used mental health services were more likely to
      commit suicide (OR = 3.07; 95% CI = 2.34-4.01) than those who had not used them.
      For African-Americans, use of mental health services was the only factor
      significantly associated with suicide (OR = 4.56 95% CI = 1.69-12.29).

PMID- 9567666
TI  - Measurement of risk for mental disorders and competence in a psychiatric
      epidemiologic community survey: the National Institute of Mental Health Methods
      for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study.
AB  - This paper describes the implementation of the National Institute of Mental
      Health Methods for the Epidemiology of Child and Adolescent Mental Disorders
      (MECA) study's goals of measuring risk factors and competence. The emphasis is on
      the development and testing of the measures. Relevant constructs for measurement
      of risk and competence in relation to psychopathology were selected and pilot
      tested prior to the field trials. A structured interview was developed and field
      tested using lay interviewers. Using the full sample from the field trials (n =
      1285 caretaker-youth pairs), sample means, standard deviations, internal
      consistencies, parent-youth agreement, and associations with childhood disorder
      were computed. Descriptive statistics reveal a range of scores and means
      consistent with norming samples, when available, Internal consistencies were
      moderate to high. Parent-youth agreement on factual items was excellent and on
      scales was consistent with the literature. Several strong associations were found
      between risk factors and disorder, although most were related to disorder in
      general and not specific to a diagnostic category. This instrument provides a
      means of obtaining data that will be useful to researchers conducting
      epidemiologic and clinical studies designed to contribute to the understanding of
      mental disorders in children and adolescents, including nosology, risk factors,
      context, adaptive functioning, and treatment.

PMID- 9567667
TI  - Unplanned first contact as a predictor of future intensive use of mental health
      services.
AB  - The scheduled appointment system, widely used in most mental health services, has
      never been evaluated. This study attempts such an evaluation within a community
      based mental health service that permits unplanned access to specialist care, by
      comparing further service use of first-episode patients who come unannounced to
      seek psychiatric care with that of patients with a planned (scheduled) initial
      appointment. All patients with first lifetime psychiatric contact who contacted
      psychiatric services reporting to the South-Verona Psychiatric Case Register
      between 1 January 1982 and 31 December 1989 (n = 1261) were identified. A total
      of 1056 patients entered the study and were followed for 2 years. Poisson
      regression with the generalised estimating equation (GEE) method (to take into
      account both overdispersion of contacts between subjects and correlation between
      contacts within subjects) was used to evaluate the effects of the type of first
      ever contact (defined as planned or unplanned according to whether or not a
      regular appointment was previously arranged) and of other selected variables,
      including sociodemographic characteristics, on the annual rate of planned and
      unplanned care in the follow-up period. Thirty-six percent of first-ever contacts
      were unplanned. Patients who began with unplanned contact, as compared with
      others, were more often widowed, separated or divorced, unemployed and with a
      diagnosis of schizophrenia or organic psychosis. Moreover, they had, in the
      following 2 years, significantly higher rates of both unplanned and planned
      community care, as well as more in-patient care (higher admission rate and a
      longer mean length of stay). These results at follow-up were confirmed when the
      rates for the type of first-ever contact were adjusted for all other clinical and
      sociodemographic variables at initial contact. Step-down Poisson multiple
      regression analysis showed that the rates of both unplanned and planned contacts
      in the follow-up period were significantly and independently associated with:
      type of first-ever contact, diagnosis and type of service first contacted.
      Unplanned cases at initial contact require particular attention and are confirmed
      as at risk for placing higher demands on mental health services in the following
      2 years. The results of the present study may also have implications for other,
      non-psychiatric health services.

PMID- 9567668
TI  - Time trends in mental health care utilization in a Dutch area, 1976-1990.
AB  - This paper concerns time trends in mental health care utilization in a Dutch area
      from 1976 to 1990. In general, there was an increase in the use of psychiatric
      services during the study period, both in terms of the number of new patients
      (per 1000 population) and in terms of the amount of care utilized per patient.
      When only intramural services were taken into account the number of new
      psychiatric patients remained approximately constant, but the number of patients
      in care at a certain point in time (point prevalence) showed a rising trend. For
      most part, the increase in inpatient point prevalence rates could be ascribed to
      the increase in the elderly population (75 years or more). In addition to the
      proportional increase of the ageing population, a growing amount of psychosocial
      problems and broadening of the concept of illness were tentatively assumed to be
      related to the increase in mental health care utilization. Unlike some other
      countries, deinstitutionalization hardly occurred in the Netherlands.

PMID- 9567669
TI  - Current combat-related disorders in the absence of PTSD among Australian Vietnam
      veterans.
AB  - The research literature on the psychiatric consequences of the Vietnam War
      focuses primarily on the construct of Posttraumatic Stress Disorder (PTSD), after
      an initial focus in the 1970s on depression and alcohol and substance abuse. The
      present paper examines the hypothesis that among men without current PTSD, those
      with higher combat in Vietnam will be more likely to have current DSM-III-R
      illnesses. The Australian Vietnam Veterans' Health Study (AVVHS) collected a
      broad range of interview data on 641 Vietnam veterans throughout 1990-1993.
      Measures of combat exposure, age at embarkation to Vietnam, enlistment IQ and pre
      Army personality problems were drawn from Army records of the era. Retrospective
      measures of combat were obtained at interview. The interview also involved the
      administration by trained lay interviewers of the DSM-III-R based Diagnostic
      Interview Schedule (DIS). This epidemiological instrument provides current
      psychiatric diagnoses as well as temporal (retrospective) symptom and diagnosis
      onset data. The results of this study show that current disorders (without PTSD
      comorbidity) with onsets within 5 years of embarkation to Vietnam are more likely
      among men who saw higher combat, as indexed by combat-exposure measures drawn
      from Army records of the era as well as retrospective self-report. This combat
      relatedness remains when age at embarkation. IQ at enlistment and pre-Army
      personality measures are used as covariates. No more than 11.4% of sampled
      Vietnam veterans currently meet DSM-III-R diagnostic criteria for PTSD, while a
      further 7.8% do not have current PTSD but do have some other current DIS
      diagnosis with onset in the 5-year period following (first) emabarkation to
      Vietnam. Our data support the hypothesis that the current illnesses of many of
      these men without PTSD are combat-related DSM-III-R illnesses.

PMID- 9567670
TI  - [The diagnostic potentials of dynamometry indices in resolving the question of
      the time of death].
AB  - Table of dynamometry values for different intervals of the postmortem period
      cannot be used in cases when livores mortis beyond the lumbosacral area are
      examined, specifically, when the corpse is found lying with the face down. The
      process of formation of livor mortis is individual and runs a specific course in
      every corpse and in its different sites. Dynamometry of hypostases can be
      informative only during the first 16 h postmortem; in later periods the time
      course of dynamometry is unstable. Dynamometry can be used only as a tentative
      diagnostic test when solving the problem of the time of death and only together
      with other methods.

PMID- 9567671
TI  - [The forensic medical assessment of age-related changes in the thyroid].
AB  - The problem of assessing the age of unidentified corpses remains a pressing one.
      Relevant published data is reviewed in brief. This study was aimed at assessing
      the possibility of using quantitative morphometric parameters of thyroid
      involution for forensic medical evaluation. The method of using these parameters
      and their mathematical processing is described. An optimal model is selected for
      assessing the biological age from two parameters, the percentage and diameter of
      follicles; this model permits the diagnosis of age with an accuracy of 88%.

PMID- 9567672
TI  - [The determination of the type of structural stability of the human skull].
AB  - A total of 819 male and female skulls (frontal sections of 250 of these) were
      examined by traditional craniometry and MBS-2 microscope in order to assess the
      variability of morphogeometric parameters of biomechanical resistance of human
      brain skull and designing its structure typology. The following types of
      construction resistance of human brain skull (craniotypes) were distinguished: 1)
      structure resistant; 2) configuration resistant; 3) morphologically resistant;
      and 4) morphologically unstable.

PMID- 9567673
TI  - [The composition and characteristics of the spread of the shot products from a
      gas-barrel weapon].
AB  - Chemical composition and diffusion of additional factors of a shot from barrel
      gun supplied with a standard chemical cartridge are studied. Experimental shots
      from gas pistols of three designs were made. During shots from gas barrel guns
      the victim is exposed to additional factors characteristic of both fire arms and
      gas barrel guns, namely, fragments of plastic cartridge container and pads,
      magnesium particles, and lacquer powder. The characteristics of the short range
      zone for gas barrel guns correspond to those of short barrel fire arms.

PMID- 9567674
TI  - [The detection and investigation of traces of biological origin by cytological
      methods].
AB  - Thirty-four expert evaluations are analyzed in 1993-1996, in which trace
      particles of animal origin were pieces of material evidence. The presence of
      cells was certified and their species, group, and organ tissue appurtenance
      identified. Expert potentialities depending on the time when the object of study
      was formed and type of examined tissue are discussed. Combined use of biological
      and cytological methods permits an informative expert conclusion in cases when
      the traditional biological methods fail.

PMID- 9567675
TI  - [The gas chromatographic analysis of volatile compounds on the compact MKhP
      chromatograph].
AB  - Methods of analysis of biological specimens, alcohol beverages, and technological
      liquids in columns with standard adsorbents carbopaque B and C with carbowax 20M,
      widely used abroad, are described and examples of analyses presented. A special
      portable chromatographer (MCP) with flame ionization detector has been designed.
      It is intended for analysis of volatile organic compounds (alcohols,
      carbohydrates, organochlorine compounds, glycols, esters, etc.) in columns of
      different polarity. The system of processing of chromatographic findings permits
      a quantitative analysis of complex chromatograms and automated identification of
      substances in biological samples by using the available database.

PMID- 9567676
TI  - [The detection and quantitative determination of lidocaine and novocainamide in
      biological fluids].
AB  - Offers methods for isolation of lidocaine and novocainamide present together in
      the urine, blood plasma, and saliva. Demonstrates the possibility of identifying
      these substances in biological fluids by thin-layer and gas liquid
      chromatography. Proposes methods for measuring lidocaine and novocainamide in
      biological objects by UV spectrometry (combined polynomial) and gas liquid
      chromatography. Demonstrates the reliability of the results.

PMID- 9567677
TI  - [The possibilities for using in forensic medical practice a chemical analysis
      unit based on the Spectroscan spectrometer].
AB  - Trials of the Russian x-ray fluorescent crystal diffraction scanning spectrometer
      Spectroscan A01 manufactured by the Spectron firm in St. Petersburg showed its
      drawbacks which can lead to erroneous interpretation of the results; this does
      not permit us to recommend this device for practical forensic medical expert
      evaluations.

PMID- 9567678
TI  - [The detection of 10-acyl derivatives of phenothiazine by staining reactions and
      a spectrophotometric method for their hydrolysis products].
AB  - Identification of phenothiazine 10-acyl derivatives by staining and
      spectrophotometry of their hydrolysis products 2-chlorophenothiazine, 2
      trifluoromethylphenothiazine, and 2-carboxyaminophenothiazine appreciably
      improved the sensitivity and specificity of their detection. Staining on silufol
      plates detects at least 0.05 to 0.15 microgram per spot. The specific parameters
      of hydrolysis products absorption are notably superior to those of the native
      compounds and are (in chloroform, U1%1 cm): 1821 for 2-chlorophenothiazine, 1400
      for 2-trifluoromethylphenothiazine, and 1656 for 2-carboxyaminophenothiazine.

PMID- 9567679
TI  - [The detection of veterinary preparations in forensic chemical investigations].
AB  - A method for detecting tetramisole from biological objects by 10% acetic acid is
      proposed. Color tests and thin-layer chromatography were used for detecting
      tetramisole in biological objects.

PMID- 9567680
TI  - [The differential diagnosis of fatal outcomes in patient treatment with
      lidocaine].
AB  - A method for isolation, identification, and measurement of lidocaine is proposed
      for investigations of biological specimens. The presence of lidocaine is
      confirmed by common alkaloid reactions, chromatography in a thin layer of
      adsorbent, and color test. Lidocaine concentration is measured by extraction
      photoelectrocolorimetry. A formula is proposed, permitting a tentative assessment
      of the injected lidocaine dose. The threshold identification value is 0.2 mg%,
      threshold detection value 0.5 mg%.

PMID- 9567681
TI  - [The morphofunctional changes in human adrenals in death from acute alcoholic
      intoxication].
AB  - Delipidation of the adrenal cortex in acute alcohol intoxication often presents
      as complete "washing" of sudanophilic and birefringent lipids (cholesterol and
      its esters) from the reticular and bundle zones. The interface between cortical
      sites devoid of and containing lipids is clearly seen as a relatively smooth
      horizontal line. Accumulations of phospholipid granules are seen in the
      protoplasm of "dark" adrenocorticocytes; the number of these granules is in
      inverse proportion to the content of cholesterol and its esters in the cell. In
      parallel with this, ascorbic acid granules in the cortical cells notably
      decrease.

PMID- 9567682
TI  - [The complete separation of the legs in the collision of a car with a
      pedestrian].

PMID- 9567683
TI  - [A highly differentiated adenocarcinoma of the large intestine as the cause of
      massive blood loss].

PMID- 9567684
TI  - [Methods for the isolation of quaternary ammonium compounds].

PMID- 9567687
TI  - [Do you have anything to hide?].

PMID- 9567688
TI  - [How to achieve a better use of antibiotics in general practice?].

PMID- 9567689
TI  - [Antibiotic resistance--a challenge for hospital hygiene work].

PMID- 9567690
TI  - [Changing birthing institutions--is it possible to select high-risk deliveries?].

PMID- 9567691
TI  - [From horizontal to vertical patients--treatment with anticoagulants in primary
      health care].

PMID- 9567692
TI  - [C-reactive protein in general practice. An important diagnostic tool in
      infections].
AB  - In just a few years C-reactive protein (CRP) has become an important test in the
      rapid elucidation of infections in Norwegian general practice. 33 general
      practitioners in the southern part of Vestfold county, continuously registered
      546 consultations where a CRP analysis was performed. The protein was analyzed in
      10% of all the consultations (range 3-31%). The general practitioners stated that
      the CRP analysis has great diagnostic impact in the elucidation of acute
      infections, but significantly less impact in routine examinations. The result
      contributed to a change in diagnosis in 30% of the patients where a diagnosis
      involving infection was considered. C-reactive protein contributed to a reduction
      in the prescribing of antibiotics in a quarter of the consultations. C-reactive
      protein is an important supplement to clinical investigation in the elucidation
      of infections in Norwegian general practice.

PMID- 9567693
TI  - [Methicillin resistant yellow staphylococci].
AB  - The incidence of methicillin-resistant Staphylococcus aureus in Norway is
      extremely low. Isolation of such strains is nearly always associated with import.
      From December 1993 to January 1997 at the Ulleval University Hospital Department
      of Medical Microbiology, methicillin-resistant Staphylococcus aureus was isolated
      from 22 persons in Oslo (17 patients and five healthy carriers). A cluster of ten
      infected persons was detected (five patients and five carriers (nurses)) who were
      infected with strains showing an unusual antibiotic resistance pattern. All of
      the cluster strains except for beta-lactams were resistant to fucidic acid and
      sensitive to other antistaphylococcal agents. The cluster was associated with two
      hospitals. The five patients were all admitted to the same intensive care unit
      during the period May to July 1995. Four of the five patients (one died) were
      referred to the same department in a long-term care hospital for rehabilitation
      and training. Problems concerning epidemiological investigation and control are
      discussed.

PMID- 9567694
TI  - [First infection with vancomycin resistant type VanA enterococci in a Norwegian
      hospital].
AB  - Enterococci are part of the normal human and animal bowel flora. They are
      considered bacteria of relatively low virulence, but are important nosocomial
      pathogens. In the context of their intrinsic resistance to a number of
      antimicrobial agents, the rapid emergence of multiresistant enterococci is
      alarming. As inhabitants of the gastrointestinal tract, they come into close
      contact with other bacteria and may pass antibiotic resistance genes to them. We
      report the first case of infection with a VanA vancomycin-resistant. Enterococcus
      in Norway. The strain was identified as Enterococcus faccium with high level
      resistance to aminoglycosides, ampicillin, teicoplanin and vancomycin. The VanA
      phenotype was confirmed by PCR detection of the vanA gene. Transmission,
      treatment, prevention, and control of infections with vancomycin-resistant
      enterococci is discussed.

PMID- 9567695
TI  - [Tularemia after tick bite in Vestfold].
AB  - Direct contact with rodents or their faeces is a well-known risk factor for
      contracting tularaemia in Norway. Both insects and ticks can act as vectors of
      tularaemia, but transmission by this route has not previously been described in
      this country. We report three cases of serologically confirmed ulceroglandular
      tularaemia on a small island in Southern Norway, an area in which tularaemia has
      not previously been known to occur. Tick bites preceded infection in two of the
      patients. The third patient may also have become infected through a tick or
      insect bite. Diagnosis was made late in all cases, causing a delay in appropriate
      treatment. Two of the patients were successfully treated with ciprofloxacin. Our
      experience and previous reports suggest that quinolones should be considered as
      the first choice of drugs in the treatment of tularaemia in Norway.

PMID- 9567696
TI  - [Better quality of thrombotest in family practice. Results from the NOKLUS survey
      1993-97].
AB  - The Norwegian centre for external quality assurance of primary health care
      laboratories (Norwegian abbreviation: NOKLUS) was established in 1992. In 1997
      about 1,800 practices participated in NOKLUS' quality assurance schemes, and 576
      of these participated in the PT survey. Participation is voluntary and free of
      charge. The interlaboratory variation (CV%) was 17.7% in 1993 and 13.3% in 1997,
      and the percentage of results classified as "poor" has decreased from 7-8% in
      1993 to 4% in 1997. These data indicate that participation in the scheme has led
      to a widespread improvement in laboratory performance. Norwegian primary health
      care practices now seem to analyse PT just as accurately as the Norwegian
      hospital laboratories. Logistic regression showed that the two most important
      factors for ensuring quality analysis were having a medical laboratory technician
      perform the PT analyses, and using an analyzer rather than a manual procedure.

PMID- 9567697
TI  - [Inflammatory bowel disease and pregnancy].
AB  - Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic
      illness, often affecting people of reproductive age. Treatment involves drugs
      which have potential side effects and because of this pregnancy causes
      considerable concern. The course of the disease is not much affected by
      pregnancy. The relapse rate is only slightly increased when the disease is active
      at the time of conception. Relapses during pregnancy should be treated in the
      usual manner. Surgical intervention should be carried out on the same indications
      as in those who are not pregnant. Frequency of complications is not increased
      during pregnancy, at delivery or post partum. Sectio may be necessary in perianal
      disease. With few exceptions, drug treatment should be continued throughout
      pregnancy. No adverse effects are seen with normal doses of sulfasalazine, 5
      amino-salicylic acid and steroids. Planned pregnancies should be started in
      periods of quiescent disease.

PMID- 9567698
TI  - [Use of 5-aminolevulinic acid in photochemotherapy and fluorescence diagnostics].
AB  - 5-aminolevulinic acid is an early intermediate product in the synthesis of heme.
      Some of the enzymes in the heme synthesis chain have altered activities in tumor
      tissue, so that application of 5-aminolevulinic acid leads to an accumulation of
      protoporphyrin IX in tumors. This molecule absorbs light and acts as a potent
      photosensitizer; tumors containing the compound can therefore be destroyed by
      light. 5-aminolevulinic acid based photochemotherapy is presently being employed
      in the treatment of thin basal cell carcinomas in many countries. The cosmetic
      result of this treatment is excellent. Furthermore, it is a simple and
      inexpensive form of treatment with curative rates comparable to those of
      established therapy modalities. Experimentally, a number of other malignant
      lesions reachable by light via optical fibers are being treated. Since
      protoporphyrin IX has a characteristic red fluorescence, 5-aminolevulinic acid
      can also be applied for diagnostic purposes.

PMID- 9567699
TI  - [Can deliveries at risk be selected at smaller delivery units?].
AB  - In order to explore the possibility of converting a delivery unit at a small
      hospital to a maternity home, we examined the medical records of those women who
      delivered by Caesarean section, forceps or vacuum extraction at Lofoten hospital
      during 1995. How many of these women might it have been necessary to transfer to
      an obstetrical department if Lofoten hospital had been a maternity home caring
      for low risk deliveries (primipara and multipara)? Out of a total of 271
      deliveries (primiparas 98), 49 women delivered by Caesarean section (n = 35),
      forceps (n = 5) or vacuum extraction (n = 9). Using risk assessment, 22 women
      (45%) would have been selected for antenatal transfer, and 20 (41%) for
      intrapartum transport. For seven women no transfer would have been possible.
      These women would have delivered locally by vacuum extraction. Primipara versus
      multipara had a relative risk of 2.8 for Caesarean section or assisted vaginal
      delivery. It is estimated that 8-9% of the women would be selected prenatally for
      planned delivery at a hospital unit and that 7-8% would be transferred in labour
      if primiparas delivered at the maternity home. If primiparas were excluded, the
      proportions would be 41% and 1-2% respectively. In 1997 the delivery unit at
      Lofoten hospital was temporarily converted to a maternity home for a period of
      two years.

PMID- 9567700
TI  - [Polymer fume fever[].
AB  - Polymer fume fever is a self-limiting condition with influenza-like symptoms
      (fever, headache, dry cough, dyspnoea and myalgia). It is caused by inhalation of
      toxic products released by combustion of fluoro-carbon polymers. There is no
      causal treatment, and the symptoms usually clear up spontaneously within 24
      hours. This article describes an accident where 13 soldiers became ill when
      exposed to fumes released from a tent oven painted with a coating containing
      fluoro-carbons.

PMID- 9567701
TI  - [Interactions between physicians and drug industry. Between Skylla and
      Kharybdis].

PMID- 9567702
TI  - [Red prescriptions].

PMID- 9567703
TI  - [Drug industry--physicians--society].

PMID- 9567704
TI  - [Diagnosis: mental retardation].

PMID- 9567705
TI  - [Diabetic care in general practice].

PMID- 9567706
TI  - [Amalgam].

PMID- 9567707
TI  - [Health services to the mentally retarded].

PMID- 9567708
TI  - [Confusion of health education!].

PMID- 9567710
TI  - [Medical theory of admission].

PMID- 9567709
TI  - [More of meaningless alternative research].

PMID- 9567711
TI  - [Typological features of cardiac regulation and emotional stress in man when
      achieving his results under test loads].
AB  - The relationship between heart rate and errors and work quality was studied in
      the examinees during somatosensory, mathematic, and Lindolt's tests. There was a
      significantly higher correlation between the time course variations of heart
      rate, the types of cardiac regulation (central, respiratory, autonomic), and the
      levels of the achieved. There was a basic difference between the groups of
      subjects in their responses to testing errors, by reflecting in altered heart
      rate and work quality.

PMID- 9567712
TI  - [Systems analysis of polyparametrical syndromes in students under study-induced
      stress].
AB  - In addition to routine physical examinations, the polyparametrical method was
      used to examine 250 students to assess their health. For this, the methods of
      pattern discrimination and classification were employed to analyze multiparameter
      data. Clinical and polymetric findings correlated well. The polymetric method
      revealed 4 main classes of the students' functional and autonomic status.
      Autonomic changes can be systemic and local. The visualized data of objective
      functional parameters controlled by the autonomic system made it possible to give
      a syndromal assessment of functional states and to reveal the intermediate stage
      between health and disease.

PMID- 9567713
TI  - [Relaxing effects of local heat-air exposure under stresses in students].
AB  - The relaxing effects of local heat-air exposures (TAE) on man (60 male students
      aged 19-21 years) were studied using a specially designed device which may
      control temperatures and time on an individual basis depending on the examinees'
      sensation of a positive emotion. On study days and under examination stress. TAE
      was shown to reduce situation-induced anxiety, to increase the duration and
      variability of R-R intervals on ECG, to make EEG right-frontal delta- and theta
      indices lower and EEG right occipital and frontal alpha-index higher. The range
      of visual accommodation increased. The findings suggest that the proposed graded
      local heat-air exposure procedure is an effective tool of relaxation and
      prevention of negative effects of emotional stress.

PMID- 9567714
TI  - [Systems analysis of colour music corrective effect].
AB  - In the context of P. K. Anokhin's theory of functional systems, the corrective
      effects of various combinations of medical therapeutical resonance music (MTRM)
      and dynamic colour exposure were analyzed. As compared to rehabilitative music
      programmes, MRTM was shown to have a more pronounced relaxing effect as
      manifested both in the optimization of emotion and in the activity of autonomic
      regulation of cardiovascular functions. On combined MRTM and dynamic colour flow
      exposures, the relaxing effect is most marked. In the examinees, the personality
      and situation anxieties diminish, mood improves, cardiovascular parameters become
      normal, the rate of metabolic processes and muscular rigidity reduce, the
      spectral power of alpha-rhythm increases, these occurring predominantly in the
      anterior region of the brain. The findings suggest the high efficiency of the
      chosen way of normalizing the functional status of man.

PMID- 9567715
TI  - [Systemic mechanisms of advanced reflection of probability events in disease].
AB  - Using the systems approach, the paper considers the nodal mechanisms and the
      value of advanced reflection of the reality (a warning response) at different
      levels of vital activity in health and disease. It is suggested that a warning
      response retains in disease, though the advanced reflection may be transformed
      depending on the severity of the body's disorders and the efficiency of
      performance of functional systems. In disease, there are three types of the
      systems: 1) usual functional systems with the same properties of warning
      responses as those in health which prevent lesions and their progression, 2)
      systems whose performance result is both useful and adverse, 3) functional
      systems whose performance result leads to impaired vital activity or contributes
      to their generalization (abnormal systems). The mechanisms of dual and damaging
      effects of the systems are disclosed. The author concludes that in disease even
      in a dying process, there are only changes in the level and, occasionally, nature
      of a warning response, but it preserves until a person is alive.

PMID- 9567716
TI  - [Autoantibodies to neurotrophic factors and perinatal brain performance disorders
      in children].

PMID- 9567717
TI  - [System approach to national health security problems].
AB  - P. K. Anokhin's basic works on functional systems, on space-time continuum and
      advanced reflection of the reality, on the physiological structure of a behavior
      act, as well as his fundamental philosophical and scientific postulated are most
      fruitful for analyzing and solving a number of biomedical, societal, and
      political problems, among them there are problems of national security in general
      and its demographic and health aspects. Individual and public health as a measure
      of balance between the organism (population) and its biosocial environment
      depends on the efficiency of relevant physiological and societal functional
      systems is one of the basic prerequisites of national security and timely
      recognition, avoiding and overcoming numerous challenges, dangers, and threats to
      the nation. General political and socioeconomic crisis in Russia adversely
      affects the population's dynamics and public health and it is manifested by
      depopulatory processes, low birth and high mortality and morbidity rates, growing
      violence and crime, psychoemotional stress, decreased immunity level of vast
      majority of population, especially that of children, elderly and other vulnerable
      groups. Environmental pollution and degradation have reached dangerous
      proportions. The national health system is unable to meet basic needs of the
      population. To overcome the crisis, systemic measures should be in the foundation
      of all health reform concepts and strategies. Monitoring national health,
      including modelling its future status, as well as progress in health system
      reforms should be another basic condition for overcoming the national health
      crisis.

PMID- 9567718
TI  - [Specific features of epidemiological situation in the Russian Federation in 1991
      1996].

PMID- 9567719
TI  - [Congenital connective tissue dysplasias].

PMID- 9567720
TI  - [The ethical and legal aspects of the activity of the anesthesiologist and expert
      in resuscitation].

PMID- 9567721
TI  - [Medical groups of special assignment in the system of treatment and evacuation
      measures in the northern Caucasus].

PMID- 9567722
TI  - [Clinical picture, diagnosis and treatment of leptospirosis].

PMID- 9567723
TI  - [The operative videothoracosopy in rendering emergency surgical care in
      penetrating gunshot chest wounds].
AB  - The modern doctrine of military surgery is based on the concept of maximal and,
      if possible, simultaneous surgical aid to the wounded in the shortest period of
      time after the injury. It could be achieved by approximation of specialized
      surgical section to the zone of fighting and improvement of medical evaluation.
      These are conditions for applicability of modern methods of treatment and for
      perfecting of surgical strategies to the wounded, such as videothoracoscopy. To
      report the experience of the usage of videothoracoscopy in the treatment of the
      wounded with penetrating gunshot wounds of chest (PFAWT) in military hospital. 23
      patients with PFWAT was administer surgical therapy: 19 patients had pleural
      draining at previous stages of medical evacuation, 4 patients were delivered
      directly from the battle Geld 1.5 hours after the injury. 11 patients with
      pleural drains and 4 patients, delivered from battle Geld, had indications for
      videothoracoscopy. These indications included ongoing intrapleural bleeding,
      clotted hemothorax and prolonged leakage of the air through the drain. Suturing
      of the lung wounds was performed by Endo-GIA-30 stapler. If it was impossible,
      manual suture EndoStitch USSC was used. In 2 cases was performed wedge-like
      resection by EndoGIA-30. The bleeding from the thoracic wall wounds was
      controlled by electrocautery. The clotted hemothorax was removed by fragmentation
      with EndoBabcock, washing out and aspiration through large diameter tubes. The
      duration of the procedure ranged from 40 to 90 minutes. None had suppurative
      complications. All patients was survived. The mean duration of inpatient period
      was 20 days, rehabilitation period-14 days.

PMID- 9567724
TI  - [Change in neutrophils in liquidators of the consequences of the accident at the
      Chernobyl Atomic Electric Power Station].
AB  - In result of own researches and analysis of the literature? the information about
      high sensitivity of neutrophils of peripheric blood to infringements of constancy
      of internal state of body, arising as reply to radiating influence, are received.
      Ionized radiation modulates greatly properties and functions of neutrophilic
      granulocytes, which are the most sensitive and high-modulated cells of non
      specific resistance system. The changes of the functional-metabolic status of
      neutrophils in participants of liquidation of consequences of Chernobyl disaster
      have been saving during 10 years after influence of the extreme, including
      radiating, factors of failure.

PMID- 9567725
TI  - [Radiation injuries of the thyroid gland].

PMID- 9567726
TI  - [Standardization of pharmacotherapy of hypertensive disease].
AB  - The consumption of the antihypertensive means in Russia and abroad is analyzed,
      the efficiency and the cost of the recommended circuits of treatment of
      hypertonic heart disease are investigated and appreciated, taking into account
      the international researches. The list of medicines, offered as the standard of
      pharmacotherapy and for supply of military-medical establishments in peace time
      is made. The offered spectrum of preparations made by a domestic industry permits
      to ensure effective and inexpensive treatment of blood hypertension according to
      circuits existing for a today's day.

PMID- 9567727
TI  - [Experience in the treatment of syphilis with benzathine benzylpenicillin].

PMID- 9567728
TI  - [The system of the operative epidemiologic analysis in the air defense medical
      service].

PMID- 9567729
TI  - [Is an index of health possible?].

PMID- 9567730
TI  - [Diagnosis and medical rehabilitation in borderline neuro-psychiatric disorders
      in flight personnel].

PMID- 9567731
TI  - [Problems of pharmacologic correction of personal endurance].

PMID- 9567732
TI  - [A device for examination of anatomic cavities].

PMID- 9567733
TI  - [Preparation of scientific-pedagogic personnel at the Military Medicine Academy].

PMID- 9567734
TI  - A comparison of the efficacy of stimulus control for medicated and nonmedicated
      insomniacs.
AB  - A sample of 21 medicated and 20 nonmedicated insomniacs participated in a sleep
      medication withdrawal program that provided education about sleep medication and
      a gradual medication withdrawal schedule. Ten medicated participants received
      stimulus control treatment and the withdrawal program, and 11 medicated
      participants served as a control group that received only the withdrawal program.
      Half of the nonmedicated participants received stimulus control, and the
      remaining nonmedicated participants served as a wait-list control condition.
      Medicated participants significantly reduced sleep medication use without
      significant deterioration on sleep, anxiety, or depression measures from baseline
      to 8-week follow-up. Stimulus control participants, unlike control group
      participants, showed significant improvement at follow-up for total sleep time,
      sleep efficiency, and sleep quality. Stimulus control participants also reported
      less daytime sleepiness than control participants after treatment. Nonmedicated
      participants exhibited a more positive response to stimulus control than
      medicated participants.

PMID- 9567735
TI  - Counselor prompts to increase condom taking during treatment for cocaine
      dependence.
AB  - This study examined whether active prompting would increase the number of free
      condoms taken from dispensers placed in counselors' offices in a cocaine abuse
      treatment clinic. Using a combined multiple baseline and reversal design, two
      teams of counselors were instructed to actively prompt and encourage condom
      taking during some conditions and to avoid commenting on or encouraging condom
      use in other conditions. To monitor accuracy of implementing the intervention,
      counselors completed a checklist for every subject they saw in their office
      during the day. Overall, the number of condoms taken per visit during prompting
      conditions was almost six times greater than during baseline conditions. However,
      implementation declined during the study, and all counselors complained about the
      intervention. Implications for dispensing free condoms to reduce HIV risk in drug
      abuse treatment clinics are discussed.

PMID- 9567736
TI  - Worry versus anxiety. Is there really a difference?
AB  - The similarities and distinctions between the constructs of worry and anxiety
      were examined in a sample of 189 university students. Three worry scales and four
      measures of anxiety were compared in relation to measures of negative affect,
      personal control, and problem-solving style. Although measures of worry and
      anxiety were highly correlated, negative affect (e.g. depression, confusion)
      tended to be more closely related to anxiety than to worry, whereas problem
      solving style tended to be more closely related to worry than to anxiety.
      Personal control did not show a differential relationship to anxiety or worry.
      When the definition of anxiety was restricted to somatic anxiety, however,
      negative affect, perceived problem-solving abilities, and personal control were
      more strongly related to worry than to anxiety. Implications of these results are
      discussed in light of current definitions and measurement of these constructs.

PMID- 9567737
TI  - Avoidance and confrontation of painful, back-straining movements in chronic back
      pain patients.
AB  - Avoidance of painful activities has been proposed to be an important risk factor
      for the initiation and maintenance of chronic low back suffering, whereas
      exposure to these activities has been suggested to be beneficial for recovery. In
      a cross-sectional study, the differences between chronic patients with avoidant
      and confrontational styles were investigated using self-report measures and a
      behavioral test. Participants were first classified as avoiders or confronters.
      In comparison with confronters, avoiders reported greater frequency and duration
      of pain, higher fear of pain and injury, more disability in daily living, and
      more attention to back sensations. Finally, avoiders reported more fear of
      (re)injury during the behavioral test and had a worse performance than
      confronters. The results suggest a close link between the fear of pain/(re)injury
      on one hand and avoidance behavior and physical deconditioning on the other hand.

PMID- 9567738
TI  - The role of symptom induction in the treatment of panic and anxiety. Identifiable
      domains, conditional properties, and treatment targets.
AB  - Although the importance of affectively charged material in the treatment of panic
      and anxiety has been emphasized and implicitly viewed as essential for effective
      therapeutic change, a general framework for organizing, understanding,
      implementing, and evaluating symptom induction techniques has yet to be offered.
      This article offers a framework for organizing symptoms induction techniques,
      categorizing treatment targets, and, accordingly, assessing therapeutic change in
      the treatment of panic and anxiety. Symptom induction techniques are examined in
      three exposure domains: physiological, cognitive, and situational/circumstantial;
      treatment targets fall into five categories: (a) poor symptom tolerance and
      resultant hypersensitivity and hypervigilance, (b) avoidance of internal and
      external triggers, (c) the emergence of specific catastrophic thoughts and
      related misinterpretations, (d) diminished adaptive coping skills, and (e) a
      reduction in general self-efficacy. Additionally, a distinction is proposed
      between conditional and unconditional properties of symptom induction, with an
      emphasis on the potential deleterious role conditional properties play during the
      course of treatment.

PMID- 9567740
TI  - Animal models in experimental diabetes mellitus.

PMID- 9567739
TI  - Fear of intimacy and attachment among rape survivors.
AB  - The purpose of the present study was to investigate attachment and fear of
      intimacy among rape survivors. As previous research has documented that several
      domains of functioning are affected by the experience of rape, it was
      hypothesized that the survivors may have difficulties with attachment and
      intimacy. Subjects were selected from an undergraduate general psychology class
      on the basis of responses to a questionnaire on sexual experiences. All of the
      subjects were female and included 44 rape survivors and 57 controls. As
      predicted, rape survivors reported greater fear surrounding intimacy. Survivors
      also differed from the controls on all of the attachment dimensions. They
      reported less confidence in others' dependability, less comfort with closeness,
      and more fear of abandonment. Trait anxiety was also controlled in the analyses,
      and except for fear of abandonment, it attenuated the differences between the
      groups such that they were no longer significantly different.

PMID- 9567741
TI  - Pharmacological basis of drug therapy of Alzheimer's disease.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder primarily
      manifesting as a loss of memory. Senile plaques and neurofibrillary tangles are
      the major histopathological alteration in the brain of Alzheimer's disease
      patients. A considerable deficiency of cholinergic neurons is a consistent
      finding in Alzheimer's disease. Therefore, many therapeutic strategies to augment
      cerebral concentration of acetylcholine such as cholinergic precursors,
      cholinergic receptor agonists, cholinesterase inhibitors and acetylcholine
      release modulators have been evaluated in Alzheimer's disease. Although
      cholinesterase inhibitors such as tacrine and galanthamine offer modest clinical
      benefits, other cholinergic agents have proved to be of limited therapeutic
      value. Efforts to enhance monoaminergic neurotransmission have also been largely
      disappointing. Therefore, emphasis is not being put on the use of combination of
      two class of drugs. Moreover, use of therapeutic agents based on the putative
      pathogenic etiology of the disease such as excitotoxicity, amyloidosis, aluminium
      accumulation, inflammatory mechanisms and free radical production is being
      evaluated. Desferrioxamine, non-steroidal anti-inflammatory drugs, prednisone,
      dapsone, vitamin E and idebenone are some such agents that are currently under
      investigation for the preventive or palliative effect in Alzheimer's disease.
      Neurotrophic factors such as nerve growth factor, brain derived neurotrophic
      factor and epidermal growth factor have shown promising results in animal
      studies. However, novel methods for delivering these molecules into the brain
      required to be developed before launching their clinical trials in man.

PMID- 9567742
TI  - Characterization of primed lymphocytes on the basic of sensitivity of chromatin
      to DNase I.
AB  - Certain qualitative criteria for primed lymphocytes in the expression of
      cytotoxic function have been studied. Unlike normal lymphocytes, primed
      lymphocytes expressed cytotoxicity even when DNA synthesis and new gene
      expression were inhibited by hydroxyurea (HU) and bromodeoxyuridine (BU)
      respectively. Such differential cytotoxic expression in presence of HU and BU by
      primed lymphocytes might have their basis in conformational change within the
      chromatin. Chromatin from primed lymphocytes was more susceptible to DNase I
      digestion than virgin lymphocytes indicating exposition of more DNase I sensitive
      sites in primed state. The result suggest the presence of more ready to act sites
      for the polymerases in the genomic material of primed lymphocytes even at
      quiescent state.

PMID- 9567743
TI  - Atropine and testosterone propionate induced atretic changes in granulosa cells
      of house rat (Rattus rattus) ovary.
AB  - Degenerative changes in membrana granulosa of ovaries in R. rattus have been
      studied using scanning electron microscopy. Ovaries from rats treated with
      atropine (300 mg/kg body weight) and testosterone propionate (10 IU) were used to
      study sequential course of atresia in granulosa cells. Granulosa cells undergoing
      atresia showed degenerative changes in following order i) loosening of
      intercellular matrix, ii) changed morphology and texture of secretory granules,
      iii) destabilization of granulosa cell membranes, iv) erosion of cell membrane,
      v) formation of specific degenerative belts, vi) pycnosis, vii) ghost cell
      formation and their subsequent mixing in hazzy follicular fluid of cyst.
      Phenomenon of atresia, its duration, course and underlying causes have been
      discussed.

PMID- 9567744
TI  - Antispermatogenic and androgenic activities of various extracts of Hibiscus rosa
      sinesis in albino mice.
AB  - The benzene chloroform and alcoholic extracts of the flowers of H.r.sinensis were
      administered (i.p.) at two different dose levels of 125 and 250 mg/kg body weight
      to adult male albino mice for 20 days. The results have shown decrease in the
      spermatogenic elements of testis and epididymal sperm count. High content of
      testicular cholesterol may be due to lowered androgen synthesis. The increase in
      the weight of accessory reproductive organs indicates the androgenicity of the
      plant extract itself, which is proved in the present study by testing the benzene
      extract in immature mice.

PMID- 9567745
TI  - In vitro propagation of Theileria annulata infected schizonts in different media
      supplemented with heterologous sera.
AB  - Efficacy of medium RPMI-1640 (supplied by Gibco USA, Centron and Hi-media)
      supplemented with horse, donkey, sheep and goat sera was evaluated for in vitro
      propagation of Theileria annulata (Hisar) infected bovine mononuclear cells. The
      results were compared with the growth rate in RPMI-1640 supplemented with foetal
      bovine serum (Gibco). RPMI-1640 (Gibco) proved to be the best medium for in vitro
      cultivation of the parasite infected cells. Foetal bovine serum could be easily,
      safely and reliably substituted with goat and sheep sera in the growth medium.
      Horse and donkey sera also gave comparable growth of T. annulata infected cells
      in vitro. Successful use of heterologous sera greatly helped in reducing the cost
      of in vitro cultivation of T. annulata schizonts. These findings have important
      implications on mass production of an attenuated cell culture vaccine for the
      control of bovine tropical theileriosis.

PMID- 9567746
TI  - Effect of chronic treatment with spirapril on biochemical parameters in
      streptozotocin-diabetic and spontaneously hypertensive rats.
AB  - Present investigation was undertaken to study the effects of 6 week treatment
      with spirapril (2 mg/kg po) on insulin sensitivity, and serum lipid levels in
      streptozotocin (STZ)-diabetic and spontaneously hypertensive (SH) rats. Treatment
      of rats with spirapril in diabetic and diabetic with hypertensive animals
      significantly prevented STZ-induced loss of body weight, hypertension, and
      bradycardia. It also partially but significantly prevented STZ-induced
      hyperglycaemia in both diabetic Wistar and SH animals. Insulin level was not
      altered by spirapril treatment. There was significant reduction in cholesterol
      levels in the diabetic rats. In conclusion, the present investigation presents a
      number of beneficial effects of spirapril treatment in diabetic and/or
      hypertensive rats. Spirapril may be considered as one of the drugs of choice in
      treatment of hypertension when associated with diabetes

PMID- 9567747
TI  - Effect of aflatoxin B in vitro on rat liver mitochondrial respiratory functions.
AB  - Isolated rat liver mitochondria were incubated with various concentrations of
      aflatoxin B (AFB) for different periods of time. Respiration rates were then
      measured with two substrates (succinate and glutamate). State 3 respiration rate
      (with added ADP) declined with increase in preincubation concentrations of AFB1
      (0.15-0.50 mM). On the other hand, state 4 respiration rate (after depletion of
      added ADP) was found to increase with increased pretreatment concentration of
      AFB. As a consequence, respiratory control index was reduced attaining minimum
      value with 0.25 mM AFB and preincubation time of 10 min. The induced anomaly in
      mitochondrial respiratory functions appear to be due to membrane damage caused by
      interaction of reactive AFB1 metabolite generated by mitochondrial cytochrome P
      450 enzymes with mitochondrial components.

PMID- 9567748
TI  - Effect of insecticidal crystal proteins of Bacillus thuringiensis var.
      israelensis on the enzymes of rat intestinal brush border membrane vesicles.
AB  - In vivo treatment of intestinal brush border membrane vesicles with solubilized
      insecticidal crystal proteins (ICP) from the two strains of B. thuringiensis var.
      israelensis (VCRC B17 and VCRC MB24) caused no adverse effect on gamma glutamyl
      transpeptidase, Na+K+ATPase, sucrase and lactase enzymes. But, exposure of
      membrane vesicles to solubilized ICP's in vitro, lead to significant reduction in
      the activity of Na+K+ATPase, sucrase and lactase enzymes.

PMID- 9567749
TI  - Status of urea and related enzymes during Plasmodium yoelii infection and
      pyrimethamine treatment in mice.
AB  - Plasmodium yoelii infection alters the hepatic levels of key enzymes of urea
      cycle, viz.carbamoyl phosphates synthetase (EC 6.3.4.16) and ornithine
      transcarbamoylase (EC 2.1.3.3) and urea levels in mice. The urea level was found
      elevated in liver, brain and plasma during P. yoelii infection. However,
      carbamoyl phosphate synthetase and ornithine transcarbamoylase were noticeably
      decreased during P. yoelii infection. Pyrimethamine treatment (10 mg/kg body
      weight for 4 days) brought back the altered parameters to normal a week after
      cessation of drug treatment.

PMID- 9567750
TI  - Studies on proteases and alpha-macroglobulin activity in amphibian blood plasma.
AB  - Frog plasma effectively hydrolysed the synthetic chromogenic substrates, H-D-Glu
      Gly-Arg-p-nitroanilide (S-2444), benzoyl-Ile-Glu-Gly-Arg-p-nitroanilide (S-2222)
      and acetyl-Ile-Glu-Gly-Arg- p-nitroanilide (S-2423), all sensitive substrates for
      trypsin. Moderate hydrolytic activities was observed with H-D-Phe-Pip-Arg-p
      nitroanilide (S-2238, substrate for thrombin) and H-D-Pro-Phe-Arg-p-nitroanilide
      (S-2302, substrate for plasma kallikrein). Frog plasma contained moderate alpha
      macroglobulin activity. When plasma was incubated at 37 degrees C, the
      macroglobulin activity decreased in a time dependent manner while only a moderate
      decrease in the protease activity was observed. Ten fold dilution of plasma with
      0.1 M phosphate buffer, pH 7.6 prevented the inherent loss of macroglobulin
      activity but it had no effect on protease activity. Dye ligand chromatography of
      the plasma on red Sepharose revealed that bulk of alpha-macroglobulin activity
      along with minor proteolytic activity (S-2222 hydrolysis) was present i the
      washings. On the other hand, about one third of the alpha-macroglobulin activity
      and bulk of the protease activity was bound to the column and were eluted with
      1.5 M NaCl. alpha-Macroglobulin activity in red Sepharose washings and elutions
      on chromatography on Sephadex G-200, was eluted in two regions with Ve/Vo value
      of 1.33 and 1.08, respectively.

PMID- 9567751
TI  - Protein A linked latex antisera test for detection of infectious flacherie of
      silkworm, Bombyx mori L. caused by B. mori infectious flacherie virus.
AB  - Protein A linked latex antisera (PALLAS) test was used for detection of B. mori
      infectious flacherie virus (BmIFV) in silkworms. The test was found superior to
      direct latex agglutination (DLA) test for detection of BmIFV in infected larval
      and faecal matter extracts and purified preparations. Latex beads sensitized with
      anti-BmIFV IgG were able to detect up to 75 ng/ml BmIFV in PALLAS test and 300
      ng/ml in DLA test. BmIFV was detected in diluted extracts of infected larvae (up
      to 1:200) and their faecal matter (up to 1:500). BmIFV progressive infection was
      detected at 12 and 24 hr of post infection in PALLAS and DLA tests, respectively
      in both larval and faecal matter extracts. PALLAS tests provides a simple,
      specific and highly sensitive test for detection of infectious flacherie virus.

PMID- 9567752
TI  - Synthesis of some new pyrimidine derivatives as potential anticancer and anti-HIV
      agent.
AB  - Several 2,4-diaminopyrimidines have been synthesized and tested for their
      anticancer and anti-HIV activities. Out of these, eight compounds displayed
      significant activity against leukemia, melanoma, non-small cell and CNS cancer.
      Two compounds were active against leukemia P388. One compound has been found to
      be moderately active as compared to AZT.

PMID- 9567753
TI  - Oxyfedrine in myocardial stunning.
AB  - Effect of oxyfedrine (OXF)(1 mg/kg) administered just before reperfusion (post
      treatment) was investigated in a canine model of myocardial stunning. In the
      saline-treated animals, myocardial stunning was evidenced by fall in MAP,
      decrease in LV peak (+) dP/dt, rise in LVEDP and incomplete regeneration of
      myocardial ATP, after reperfusion. OXF was found to be effective in preventing
      the haemodynamic and metabolic changes associated with myocardial stunning.

PMID- 9567754
TI  - Lysine: arginine ratio of a protein influences cholesterol metabolism. Part 1-
      Studies on sesame protein having low lysine: arginine ratio.
AB  - The effect of globulin fraction with a lysine: arginine (lys:arg) ratio 0.67,
      isolated from sesame (Sesamum Indicum) seeds on cholesterol metabolism was
      studied in rats fed cholesterol free and cholesterol containing diet and compared
      with casein (lys:arg ratio-2.0). Rats fed sesame seed globulin showed
      significantly lower concentrations of cholesterol in the serum and aorta. The
      decrease in serum was manifested in both HDL and LDL + VLDL fractions. There was
      increased cholesterogenesis in the liver as was evident from increased
      incorporation of labeled acetate into cholesterol and increased activity of 3
      Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Increased hepatic diversion of
      cholesterol to bile acid synthesis and increased fecal excretion of bile acids
      and sterols were also observed in rats fed sesame seed globulins. Rats fed sesame
      globulins also showed significantly higher activity of lipoprotein lipase in the
      heart and adipose tissue and that of plasma Lecithin: cholesterol acyltransferase
      (LCAT). These studies suggest that low lysine: arginine ratios of a protein exert
      hypocholesterolemic effects.

PMID- 9567755
TI  - Effect of mycotoxins isolated from Penicillium nigricans on glucose-6-phosphate
      dehydrogenase.
AB  - A new mycotoxin product (NMP) was isolated from the culture of mutated wild
      strain of P. nigricans which is less toxic and has sterol derivative. NMP (LD50 >
      1 g/kg) showed antimicrobial and antineoplastic activities and does not affect
      the hematological parameters like RBC count and hemoglobin. It maintained normal
      blood glucose level by increasing the enzyme activity of glucose-6-phosphate
      dehydrogenase (EC-1.1.1.49; G-6-PDH) by 30%. It also maintained the normal ion
      balance in the blood of mice. NMP decreased Km value of glucose-6-phosphate
      dehydrogenase and thus increased substrate affinity of the enzyme. Reduction of
      toxicity of NMP has been well explained by higher activity of G-6-PDH which is
      highly specific for production of NADPH.

PMID- 9567756
TI  - Production of triploid transgenic zebrafish, Brachydanio rerio (Hamilton).
AB  - Eggs of zebrafish Brachydanio rerio were heat-shocked just after fertilisation to
      induce triploidy and subsequently subjected to microinjection with the linear
      recombinant plasmid containing the Rous Sarcoma Virus-Long Terminal Repeat (RSV
      LTR) promoter linked to the rainbow trout (Oncorhynchus mykiss) growth hormone
      (GH)cDNA(pRSVrtGH). Slot and Southern analyses showed the extra chromosomal
      transfer of pRSVrtGH. Expression of pRSVrtGH was detected in the triploid
      transformants by RNA slot, Northern and Western analyses.

PMID- 9567757
TI  - Effect of ibuprofen and diclofenac sodium on experimental would healing.
AB  - Effects of frequently used anti-inflammatory drugs ibuprofen and diclofenac was
      studied on experimental wound healing in rats. These drugs impede tissue repair
      by virtue of retarding inflammation. There was 16-36% reduction in wound strength
      measured in terms of tensile strength in experimental rats. The detrimental
      effect of anti-inflammatory drugs was confirmed by histological examination of
      wound and by measuring dry granuloma weight.

PMID- 9567758
TI  - Effect of diuron on germ cells of mice.
AB  - Diuron in both, acute (340 and 170 mg/kg body wt) and chronic (3400 ppm) doses
      induced dominant lethal mutations in male Swiss albino mice. The results suggest
      that diuron is mutagenic in dominant lethal test system.

PMID- 9567759
TI  - Autoantigen Ku and its role in multiple cellular processes.
AB  - Ku is a DNA binding protein composed of 70 and 80 kDa subunits which was
      discovered as autoantigen in a patient with scleroderma-polymyositis overlap
      syndrome. Ku can bind to the end of DNA and also to some internal sequences. Ku
      autoantigen acts as a potential transcription factor for several RNA polymerase
      II genes and RNA polymerase I gene. Ku is also associated with DNA-dependent
      protein kinase and involved in V(D)J recombination and DNA break repair
      mechanisms. Ku may be involved in replication, helicase activity and cell
      signaling. Therefore, Ku-autoantigen is a very important cellular factor which
      plays important role in the multiple cellular processes.

PMID- 9567760
TI  - Micromanipulation and cloning studies on buffalo oocytes and embryos using
      nucleus transfer.
AB  - An investigation for testing the viability of production of cloned buffalo
      embryos through nucleus transfer has been made. Matured buffalo oocytes, after
      zona cutting to an extent of 60 degrees near polar body, were enucleated using a
      new approach. Instead of aspirating the cytoplasm contents in a pipette, the half
      of cytoplasm of oocyte was pushed out, thereby also taking away the nuclear
      material of the oocyte, leaving the demi-oocyte with the zona pellucida
      enucleated. The absence of fluorescence confirmed the success of the enucleating
      process. For enucleating, the oocytes which had intact plasma membrane were
      eligible for bisectioning. There was no significant difference in oocytes having
      intact membrane among grade I (33.9%) and grade II (31.4%) oocytes, whereas lower
      percentage of grade III oocytes had a very low percentage having intact plasma
      membranes (8.5%). The hours of maturation for 32, 37 and 42 did not influence the
      per cent oocytes which had intact membranes. All the bisected or demi-oocytes
      tested with fluorescence screening yielded successful enucleation in 88.2% demi
      oocytes. The temporal effect of three maturation hours of 32, 37, and 42 hr; two
      electrical pulse numbers of 2 and 3 pulses and two magnitudes of electric pulses
      of 15 and 20 V were studied for their effect on the percentage of successful
      fusion of demi-oocyte blastomere complexes and the rate of complexes undergoing
      cleavages. The time period for which the oocytes were subjected to the process of
      maturation significantly affected the per cent fusions and per cent cleavage of
      the demi-oocyte blastomere complexes and 32 hr maturation yielded less fusions
      (38.5%) compared to maturation for 37 and 42 h (53.2 and 57.8%, respectively).
      The treatment of either 2 or 3 electrical pulse numbers resulted in significantly
      different fusion (45.6 and 54.1%) as well as cleavage rates (18.2 and 26.1%) of
      demi-oocyte-blastomere complexes electrofused. The treatment of two levels of
      magnitude of 15 and 20 V of an electric current resulted in similar per cent
      fusion (48.0 and 51.6%) and cleavage rates (21.0 and 23.2%). Fortified TCM with
      either 10 or 20% FBS for culturing freshly electrofused complexes for 1 hr did
      not differ significantly with respect to per cent complexes fused and cleaved,
      giving a fusion rate of 46.2 and 53.8% and cleavage rate of 21.2 and 23.2% for
      10% and 20% FBS, respectively. Production of cloned embryos through the process
      of nuclear transfer has been accomplished. The successful cleavages of the
      nuclear transferred oocytes demonstrated the viability of enucleation procedures
      of the oocytes and technology implementation of electrofusion in buffalo oocytes.

PMID- 9567761
TI  - Effect of prenatal haloperidol administration on anxiety patterns in rats.
AB  - Haloperidol (0.1 mg/kg, i.p.) treatment was given from day 12 to 20 of gestation
      to pregnant rats, this being the critical period for neural development in this
      species. The pups born were subjected to open-field exploratory behaviour, tunnel
      board exploratory behaviour, elevated zero-maze and elevated plus maze behaviour
      tests at 7-8 weeks of age. The results indicate that prenatal haloperidol
      treatment induces a significant increase in open-field ambulations and rearings,
      decrease in scratching and licking/washing behaviours whereas grooming and faecal
      droppings remain unchanged. Significantly reduced activity in the centre and
      increased activity in the periphery of the tunnel board was noted. These suggest
      presence of anxiety in these animals. Significant anxiogenic behavioural patterns
      were also observed on elevated zero-maze and plus-maze in the prenatally
      haloperidol treated offsprings. The results suggest that prenatal exposure of
      haloperidol leaves a lasting effect on offsprings resulting in hyper-emotional
      responsiveness and anxiety state.

PMID- 9567762
TI  - Effect of postweaning nutritional and environmental restrictions on
      discrimination learning in albino rats.
AB  - Charles Foster littermate albino rats (72) were randomized into 9 independent
      groups in a 3 x 3 factorial design by varying nutrition and environment each at
      three levels: normal nutrition, 25% nutritional restriction and 50% nutritional
      restriction; normal environment, 3-week environmental restriction and 6-week
      environmental restriction. The nutritional and environmental restrictions were
      imposed from the 30th day of life for 6 weeks. The animals were subsequently
      tested for black/white original learning followed by reversal discrimination
      learning in a T-maze. The results indicated significant main effects for
      nutrition and environment on indices of learning ability. However, the nutrition
      x environment interaction was not significant. Post hoc analysis revealed that
      moderate and severe nutritional restriction as well as long-term environmental
      restriction caused significant discrimination learning deficits. Short-term
      environmental restriction failed to produce significant effect on learning
      behaviour. The results are discussed in context of environmental stress effects,
      altered brain mechanisms and psychological changes such as increased drive level
      and emotionality of the animal.

PMID- 9567763
TI  - Haloperidol-induced catalepsy: a model for screening antidepressants effective in
      treatment of depression with Parkinson's disease.
AB  - Incidence of severe depression is very common in Parkinson's disease (PD). Use of
      antidepressants in such cases is known to improve or worsen the existing PD.
      However, prediction of the effect of antidepressant on symptoms of PD is limited
      due to lack of suitable animal model. The present study examines the possibility
      of using haloperidol-induced catalepsy model in rats for this purpose.
      Antidepressants showed distinct effect on haloperidol-induced catalepsy, although
      most of them reduced forced-swimming induced immobility. In general,
      antidepressants with greater noradrenergic reuptake inhibition (desipramine,
      imipramine, amitriptyline, nortriptyline, protriptyline and maprotiline) reduced,
      whereas those with serotonergic reuptake inhibition (fluoxetine and clomipramine)
      increased haloperidol-induced catalepsy. Mianserin, an atypical antidepressant,
      and alprazolam, a benzodiazepine receptor analogue had no effect on haloperidol
      induced catalepsy. The results suggest that haloperidol-induced catalepsy model
      in rats needs to be incorporated in the screening procedure when evaluating the
      utility of antidepressant drugs for the treatment of depression associated with
      PD.

PMID- 9567764
TI  - Protective effect of picroliv, active constituent of Picrorhiza kurrooa, against
      oxytetracycline induced hepatic damage.
AB  - Picroliv, the active constituent of P. kurrooa, showed a dose dependent (1.5-12
      mg/kg, po for 7 days) hepatoprotective activity against oxytetracycline induced
      hepatic damage in rat. It increased the number of viable hepatocytes (ex-vivo)
      significantly. Increase in bile volume and its contents in conscious rat suggests
      potent anticholestatic property. Picroliv also antagonised alterations in enzyme
      levels (GOT, GPT, and alkaline phosphatase) in isolated hepatocytes and serum,
      induced by oxytetracycline (200 mg/kg, i.p.) feeding. Picroliv was more potent
      than silymarin a known hepatoprotective drug.

PMID- 9567765
TI  - Hepatoprotection with Glycosmis pentaphylla (Retz).
AB  - Effects of extracts of leaf (250, 500 and 750 mg/kg body wt) and stem bark (100,
      200 and 400 mg/kg body wt) of G. pentaphylla were studied on CCl4 (1 mg/kg body
      wt) induced hepatic injury in albino rats. Parameters studied were plasma ALAT,
      ASAT, ALP, total bilirubin and tissue histopathology. Recovery of hepatic tissue
      was indicated with the highest dose (750 mg/kg body wt) of leaf extract. The
      therapeutic dose range was devoid of toxic effects. Toxicity of leaf extract was
      observed histopathologically at and above 2.5g/kg body wt.

PMID- 9567766
TI  - Antiinflammatory and antipyretic activity of Michelia champaca Linn., (white
      variety), Ixora brachiata Roxb. and Rhynchosia cana (Willd.) D.C. flower extract.
AB  - Methanolic extracts of the flowers of M. champaca, I. Brachiata and R. cana were
      found to possess antiinflammatory activity against cotton pellet granuloma in
      rats at a dose level of 100 mg/kg body weight, sc. The latter two drugs showed
      higher activity (AIA) as compared to that of M. champaca. They reduced the
      protein content, acid phosphatase, glutamate pyruvate transaminase and glutamate
      oxalo-acetate transaminase activities in liver and serum. A significant reduction
      in the ascorbic acid content in adrenals was also observed in drug-treated
      animals. R. cana was recorded to possess significant antipyretic activity from
      the first hour of administration. These pharmacological properties may be traced
      to the presence of flavonoids in the flowers of these plants.

PMID- 9567767
TI  - Antilymphocytic and immunosuppressive effects of Lantana camara leaves in rats.
AB  - Once daily administration of Lantana camara leaves juice at different dose levels
      (60, 300, 600 and 1500 mg/kg/day) for 14 days in rats resulted in alterations in
      various haemato- and biochemical parameters. Significant increase in blood urea
      nitrogen was observed with the doses of 600 and 1500 mg while significant
      increase in the relative weights of adrenals was observed at all the four dose
      levels. Total proteins, globulins, absolute lymphocyte count and per cent
      lymphocyte count were significantly decreased with 60, 600 and 1500 mg doses
      while a significant hypoglycemic effect was observed with 1500 mg only. Rats
      treated with 1500 mg dose did not exhibit any increase in alanine
      aminotransferase and aspartate aminotransferase activities or the alterations in
      relative kidney and liver weights. In another set of experiment, once daily oral
      administration of 1500 mg/kg/day for 14 days significantly inhibited the
      granulomatous tissue formation in rats and this effect was comparable to that of
      cyclophosphamide (10 mg/kg/day).

PMID- 9567768
TI  - Immunopotentiating activity of septilin.
AB  - Oral administration of septilin (100mg/animal/dose; five doses) was found to
      enhance natural killer cell mediated cytotoxicity and antibody-dependent cellular
      cytotoxicity in normal mice as well as tumour-bearing mice. Septilin treatment
      also activated the peritoneal macrophages which produced cytotoxicity to L929
      cells. Septilin increased proliferation of bone-marrow cells and there was an
      increase in the number of alpha-naphthyl acetate esterase staining cells in the
      bone-marrow. In addition to the activation of cellular immunity, septilin was
      found to increase the number of antibody producing cells in the spleen and
      activation of antibody-dependent complement-mediated cell lysis. These studies
      justifies the use of this herbal preparation in improving immunocompetence in
      disease states.

PMID- 9567769
TI  - In vitro transcorneal permeation of ketorolac from oil based ocular drops and
      ophthalmic ointment.
AB  - Transcorneal permeation of ketorolac from oil based ocular drops and ophthalmic
      ointments was studied in vitro, using goat cornea. Cumulative (%) permeation of
      ketorolac through cornea, was found to be maximum with 0.2% (w/v) ketorolac drops
      in sesame oil followed by formulations in corn oil and soyabean oil. Ketorolac 1%
      (w/v) drops in castor oil increased the quantity permeated but cumulative (%)
      permeation was less. Permeation profiles of ketorolac were in consistence with
      the partition characteristic of drug between oil and aqueous phase. Formulations
      favouring corneal permeation of ketorolac increased corneal hydration. Addition
      of benzyl alcohol, a preservative, to oil drops reduced permeation of ketorolac
      and corneal hydration indicating possible protective effect of benzyl alcohol
      against corneal damage. Permeation studies on ointment formulations containing
      either ketorolac acid or ketorolac tromethamine salt indicated better permeation
      for formulation containing ketorolac tromethamine aqueous solution. Thus for
      better transcorneal permeation, ketorolac 0.2% (w/v) drops, formulated in sesame
      oil, containing 0.5% v/v benzyl alcohol and ophthalmic ointment containing 0.5%
      (w/w) ketorolac tromethamine in dissolved state appear suitable.

PMID- 9567770
TI  - Expression of Rhizobium meliloti symbiotic promoters in Azorhizobium caulinodans.
AB  - Plasmids containing Rhizobium meliloti symbiotic promoters P1 (promoter of
      nifHDK) and P2 (promoter of fixABCX) when mobilized into the cells of
      Azorhizobium caulinodans strain IRBG 46 showed strong expression of these
      promoters under free-living microaerobic as well as symbiotic conditions. Under
      free-living conditions microaerobiosis (3% or less O2) was found to be sufficient
      to activate these promoters; expression being higher at 1% than at 3% O2
      concentration. Under symbiotic conditions the expression was much more stronger
      with bacteroids in stem nodules showing higher expression than those in root
      nodules. Under both the conditions expression of the promoters in the native R.
      meliloti strain Rm102F34 was lower than that in the A. caulinodans strain IRBG
      46. The results suggest a functional homology of these promoters in the
      heterologous background of A. caulinodans.

PMID- 9567771
TI  - In vivo effects of a single dose of norepinephrine and epinephrine on tissue
      respiration of hibernating and non-hibernating species of frogs.
AB  - In vivo effects of a single dose of norepinephrine (NE) and epinephrine (EP) were
      studied on the rate of tissue (liver and skeletal muscle) respiration in Rana
      limnocharis (hibernating Sp.) and Rana cyanophlyctis (non-hibernating Sp.) during
      winter and summer months after 10 and 30 min, 1, 6, 12 and 24 hr of
      administration. During winter both NE and EP induced significant increase in the
      rate of tissues respiration only after 30 min after their administration in both
      the species and the stimulatory effect lasted up to 6 hr. During summer, however,
      NE and EP stimulated respiratory rate of tissues comparatively after a shorter
      lag period (10 to 30 min) in R. limnocharis than that of R. cyanophlyctis (30 min
      to 6 hr). These findings seem to suggest that NE and EP can stimulate tissue
      respiration very quickly, and, therefore, might be suitable as emergency hormones
      for instant/faster stimulation of energy metabolism in amphibians.

PMID- 9567772
TI  - Body size, mating success and advantage of large flies in Drosophila bipectinata
      species complex.
AB  - Mating success of large and small flies of Drosophila malerkotliana and D.
      bipectinata was studied using multiple, male and female choice methods. In
      multiple choice method the large male mated with large female and small male
      paired with small female. In female choice method, large male was successful in
      mating with female irrespective of its size while in male choice method,
      preferential mating occurred between large male and large female as well as small
      male and small female. The consequence of such non-random mating in the presence
      of male rivarly and preferential mating has been discussed.

PMID- 9567773
TI  - Effects of acrolein on rat liver antioxidant defense system.
AB  - Effect of acrolein (2.5 mg/kg body wt/day) on the rat liver antioxidant defense
      system was investigated. Following 45 days of acrolein exposure, the levels of
      glutathione, ascorbic acid and the activity of catalase were decreased whereas
      the activities of superoxide dismutase and glutathione peroxidase were increased.
      The increase in the level of thiobarbituric acid reactive substances in the
      acrolein treated rats showed oxidative damage. The results indicate that acrolein
      interferes with the antioxidant defense system of rat liver.

PMID- 9567774
TI  - Triiodothyronine (T3) and thyroxine (T4) levels in Rana curtipes during
      development and metamorphosis.
AB  - During premetamorphosis, levels of circulating triiodothyronine (T3) and
      thyroxine (T4) were below the limits of detection of RIA. They became detectable
      in late prometamorphic stages. A gradual increase in T3 and T4 was observed
      during this period. A sharp rise in hormone levels was apparent at the onset of
      metamorphic climax. Peak levels of both hormones were found at Taylor-Kollros
      stage XXI. The T3 reached a peak level of 101.4 ng/dl, about 3 fold increase over
      the level at prometamorphosis. Thereafter the circulating hormones (particularly
      T4) decreased rapidly and reached levels similar to prometamorphic stages.
      Significant high levels of thyroid hormones (T3 and T4) in metamorphic climax
      suggest that like other anurans, elevation of these hormones is required for
      normal metamorphosis in R. curtipes tadpoles.

PMID- 9567775
TI  - Raman optical activity: an incisive new probe of the structure and dynamics of
      biomolecules.
AB  - Determination of the solution structure and function of biomolecules such as
      proteins, carbohydrates and nucleic acids remains at the forefront of biomedical
      research. Thanks to recent developments in instrumentation, biomolecules can now
      be studied using Raman optical activity (ROA), a novel technique which measures
      vibrational optical activity in chiral molecules by means of a small difference
      in the intensity of Raman scattering in right- and left-circularly polarized
      incident laser light. This article reviews recent progress in the application of
      ROA to the determination of the solution structure and dynamics of proteins,
      carbohydrates and nucleic acids.

PMID- 9567776
TI  - Plants under attack II.
AB  - In many diseases of plants there is a well defined genetic relationship between
      host and pathogen, the host possessing resistance genes and the pathogen
      possessing avirulence genes. Where these are cognate their products interact and
      trigger a variety of resistance responses, resulting in an incompatible
      interaction. Where they are not cognate the pathogen is not recognised and
      invades the host causing a compatible interaction. A few resistance genes and a
      larger number of avirulence genes have been cloned and this information has
      afforded us new perspectives of the recognition phenomenon itself and the means
      by which virulent pathogens avoid being recognised. Mechanisms of resistance
      range from preformed antimicrobial compounds to a series of components that are
      induced as a response to microbial challenge. Most of these induced reactions are
      preceded by and may be triggered by an oxidative burst which results in the cross
      linking of cell wall proteins and also causes the death of one to several cells.
      This localized death of host cells, termed the hypersensitive response, provides
      an explanation for resistance to obligate parasites which require living host
      tissue but not for resistance to facultative parasites which colonise dying or
      dead tissue. However, the hypersensitive response appears to be intimately
      involved with several other defence responses such as the synthesis and
      accumulation of phytoalexins, lignification and the production of hydrolase
      enzymes that attack the invader. Salicylic acid has proved fundamental to the
      effecting of these defence responses and also to the phenomenon of systemic
      acquired resistance whereby a previous challenge from a pathogen induces the
      expression of enhanced resistance to a second challenge by the same or another
      organism. Despite these sophisticated defences plants still succumb to attack.
      Two of the weapons to which they are vulnerable and which are produced by many
      successful pathogens are toxins and enzymes. In some instances an understanding
      of these has pointed to novel methods of control supplementary to that obtained
      by conventional breeding for resistance.

PMID- 9567777
TI  - Recent advances in biology: intercellular communication and quorum sensing in
      micro-organisms.
AB  - N-acyl-L-homoserine lactones are involved as intercellular signalling agents
      controlling a wide range of physiological responses in Gram-negative bacteria.
      They function especially in vibrios, pseudomonads and erwinias as well as in
      Rhizobium and Agrobacterium spp, particularly where the bacteria are in symbiotic
      or parasitic relationships with higher organisms. Several Gram-negatives, such as
      Escherichia coli, do not, however, appear to produce or respond to AHLs and they
      may have other intercellular signalling molecules. The present review reports
      that several stress related responses in E. coli can be induced by supernatant
      fluids from cultures which have already induced the response. In some cases at
      least, the active agents in the supernatant fluids are proteins rather than AHLs.

PMID- 9567778
TI  - HIV incidence and prevalence beginning to decline.

PMID- 9567779
TI  - Update: crown and bridge. Interview by Phillip Bonner.

PMID- 9567780
TI  - Porcelain veneers as an option for lower anterior dentition.

PMID- 9567781
TI  - Preliminary stabilization of full denture implant patients.

PMID- 9567782
TI  - Non-axial implant placement to avoid the maxillary sinus.

PMID- 9567783
TI  - Prophylactic antibiotics.

PMID- 9567784
TI  - Sharper image: next generation intraoral cameras.

PMID- 9567785
TI  - Air abrasion: the new standard of care.

PMID- 9567786
TI  - Dental laboratory excellence can help build a successful practice.

PMID- 9567787
TI  - Hiring, evaluating your hygienist.

PMID- 9567788
TI  - Laser tooth whitening.

PMID- 9567789
TI  - The crown-down technique: a paradigm shift. Interview by Donald E. Arens.

PMID- 9567791
TI  - Effectively using the three-wire tip edge.

PMID- 9567790
TI  - How to double orthodontic success.

PMID- 9567792
TI  - Options for aesthetic conservative Class I restorations.

PMID- 9567793
TI  - A check of cheeks.

PMID- 9567794
TI  - OSHA and dentistry: a progress report.

PMID- 9567795
TI  - Re-engineering infection control: trends, techniques and technologies.

PMID- 9567796
TI  - The dental waterline controversy.

PMID- 9567797
TI  - Simple scheduling techniques for better production and stress reduction.

PMID- 9567798
TI  - Update on restorative materials: an exclusive interview with Dr. Dan Nathanson.
      Interview by Phillip Bonner.

PMID- 9567799
TI  - Dentinal bonding as a desensitizing agent and composite resin provisionals.

PMID- 9567800
TI  - Mastering the art of indirect composite restorations, Part 2.

PMID- 9567801
TI  - A rational approach to perio-endo.

PMID- 9567802
TI  - Facial aesthetics without plastic surgery: the cosmetic dentistry alternative.

PMID- 9567804
TI  - Voice recognition technology: the voice of the future in dental computing.
      Interview by Cheryl Farr.

PMID- 9567803
TI  - Occlusion's role in TMD problems? An interview with Dr. Robert Kerstein.

PMID- 9567805
TI  - Solving anterior crowding with a resin-bonded bridge.

PMID- 9567806
TI  - Medical myths of clinical dentistry: endocarditis.

PMID- 9567807
TI  - Combating cross-contamination between dental labs and offices.

PMID- 9567808
TI  - Ten steps to no-shows and cancellations: the team approach.

PMID- 9567809
TI  - Guidelines for implementing the ideal day scheduling system.

PMID- 9567810
TI  - Current trends in dental benefits plans.

PMID- 9567811
TI  - Gold: is it still the standard for restorative dentistry?. Interview by Phillip
      Bonner.

PMID- 9567812
TI  - Early bone loss etiology and its effect on treatment planning.

PMID- 9567813
TI  - A simplified technique for treating mandibular edentulism.

PMID- 9567814
TI  - Restoring interdental papillae for maximum aesthetics.

PMID- 9567815
TI  - The greatest marketing tool ever: practice what you preach.

PMID- 9567816
TI  - Smile design terminology.

PMID- 9567817
TI  - Cosmetic dentistry and anterior guidance: a comprehensive approach.

PMID- 9567818
TI  - Optimal obturation and shaping.

PMID- 9567819
TI  - Multimedia: the gateway to better patient education.

PMID- 9567820
TI  - Mitral valve prolapse.

PMID- 9567821
TI  - Screening for temporomandibular disorders.

PMID- 9567822
TI  - Production and profit.

PMID- 9567823
TI  - Additional techniques for effective scheduling.

PMID- 9567824
TI  - Oral surgery for the general practitioner. Interview by Phillip Bonner.

PMID- 9567825
TI  - Endoscopic surgery: an alternative technique.

PMID- 9567826
TI  - Bar-supported overdentures.

PMID- 9567827
TI  - Uses for titanium anchors in bridge work.

PMID- 9567828
TI  - A problem-solving impression technique.

PMID- 9567829
TI  - Distraction osteogenesis.

PMID- 9567830
TI  - Diet and caries.

PMID- 9567832
TI  - Dentist-laboratory connection: one key to treatment excellence. Interview by
      Phillip Bonner.

PMID- 9567831
TI  - Hybrid posterior composite restorations: a simplified procedure with
      anticariogenic properties.

PMID- 9567833
TI  - Beware of your chair: sitting down is not enough!

PMID- 9567834
TI  - Practice behaviors and attitudes of U.S. practices.

PMID- 9567835
TI  - Power in scaling: the sonics and ultrasonics.

PMID- 9567836
TI  - How to buy the perfect dental computer.

PMID- 9567837
TI  - Treating halitosis: a new opportunity.

PMID- 9567838
TI  - Study links failure of anti-HIV drug to patients.

PMID- 9567839
TI  - Preserving fee-for-service dentistry.

PMID- 9567840
TI  - The art of endodontics: selected case histories, Part 1.

PMID- 9567841
TI  - Current dental chemotherapeutics.

PMID- 9567842
TI  - Scaling and root planing: effective therapeutic modalities. Interview by Phillip
      Bonner.

PMID- 9567843
TI  - High-tech periodontics: new weaponry for scaling back periodontal disease.

PMID- 9567844
TI  - Connective-tissue root coverage using microsurgery.
AB  - Use of the operating microscope and microsurgical instrumentation has made
      possible modifications in conventional root coverage procedures that eliminate
      vertical incisions, papillary elevation, and secondary intention wound healing.
      Greater precision in incisions and suturing done with microsurgery allows
      clinicians to obtain predictable root coverage with more aesthetic postoperative
      results and reduced patient discomfort.

PMID- 9567845
TI  - A taste of tongues.

PMID- 9567846
TI  - Managing erosion associated with bulimia nervosa.

PMID- 9567847
TI  - Temporary beauty: achieving optimal results.

PMID- 9567848
TI  - Introducing dentistry to the 21st century via the intraoral camera.

PMID- 9567849
TI  - Time management. Ideal scheduling concepts for reduced stress and increased
      production.

PMID- 9567850
TI  - Financial policy is the key to the bottom line.

PMID- 9567851
TI  - The art of the close.

PMID- 9567852
TI  - Predictable porcelain laminate veneers.

PMID- 9567853
TI  - A multi-disciplinary approach to cosmetic problems.

PMID- 9567854
TI  - Three-quarter porcelain veneers.

PMID- 9567855
TI  - Advanced techniques in porcelain veneering: orthodontic realignment with veneers.

PMID- 9567856
TI  - A conservative approach to regaining aesthetics and function.

PMID- 9567857
TI  - An interdisciplinary approach to implant therapy. Interview by Phillip Bonner.

PMID- 9567858
TI  - Hinged tripodal subperiosteal implants for severely atrophied mandibles.

PMID- 9567859
TI  - The art and science of computer imaging.

PMID- 9567860
TI  - Endodontic isolation and radiography.

PMID- 9567861
TI  - All-ceramic restorations in everyday practice.

PMID- 9567862
TI  - Objective electronic measurement, Part II.

PMID- 9567863
TI  - Placing and finishing aesthetic restorations.

PMID- 9567864
TI  - What you need to know about the Internet.

PMID- 9567865
TI  - How to have your hygienist (and staff) be a valuable team member.

PMID- 9567866
TI  - Clinical assistants. The key to sophisticated scheduling.

PMID- 9567868
TI  - One-visit endodontics: a new model of reality.

PMID- 9567867
TI  - Drug shows potency against HIV.

PMID- 9567869
TI  - Microendodontics: eliminating intracanal obstructions.

PMID- 9567871
TI  - The residual endodontic space: its use in achieving optimal post-core retention.

PMID- 9567870
TI  - Bonded post-endodontic rehabilitation.

PMID- 9567872
TI  - All-ceramic anterior fixed restorations: a most natural approach.

PMID- 9567873
TI  - Reattaching salvageable crowns.
AB  - The technique of reattachment of broken, but otherwise intact, crowns is one
      worth exploring. The time constraints placed upon the dentist to evaluate this
      type of emergency patient can be quite burdensome. The technique offers an
      alternative solution to this problem. As dental practitioners, our first reaction
      to this type of emergency situation might include a series of logical steps to
      restore the tooth. These steps might include a new core build up with pins, then
      onto a temporary crown. A second alternative might be to initiate root canal
      therapy and manufacture a temporary post and crown. Still another option may
      include extraction of the tooth and an impression for an interim partial denture,
      later to be replaced by implant supported crowns, removable partial denture, or
      other prosthesis. Adding reattachment of the broken crown back onto the tooth
      gives just one more alternative to an otherwise lengthy and difficult set of
      possible solutions. Most of the more conventional types of treatment listed above
      can be quite time-consuming. Multiple appointments may be needed, and the shock
      in learning this reality may be overwhelming to the patient. Quite often, a
      patient that is in need of reattachment of a crown will have many other dental
      needs. Exhausting a patient's finances, as well as their time limits in restoring
      just one tooth may not be prudent. It may make more sense to repair, if only
      temporarily, one tooth and to go on to the next most pressing dental concern.
      Reattachment of the crown, although not always an easy solution, can be learned,
      and with practice, the technique can be expanded to include more difficult cases,
      including fractured bridges,and teeth with broken posts. These methods can be
      performed in one appointment with a high degree of success. Although it is best
      to advise the patient of the temporary nature of the treatment, it is quite
      likely that the repair will hold up almost as well as the original project.

PMID- 9567874
TI  - An alternative to crown-and-bridge: restoration of an anterior malalignment.

PMID- 9567875
TI  - Achieving predictable results with posterior inlays and onlays.

PMID- 9567876
TI  - Maximizing the use of indirect composite restorations.

PMID- 9567877
TI  - Cyberknife: dental lasers enter the 21st century.

PMID- 9567878
TI  - How does your hygiene department measure up?

PMID- 9567879
TI  - Indoor air quality and the dental operatory.

PMID- 9567880
TI  - On the Internet: education on the information highway.

PMID- 9567881
TI  - Refining scheduling systems: is anesthetic time 'captive' or 'free'?

PMID- 9567882
TI  - New frontiers in pain management. Interview by Cheryl Farr.

PMID- 9567883
TI  - Update on antibiotics in dentistry. Interview by Phillip Bonner.

PMID- 9567884
TI  - Pain management in dentistry.

PMID- 9567885
TI  - Pulpotomy: the old reliable pulp therapy.

PMID- 9567886
TI  - Fifth-generation bonding systems. Predictable posterior composite restorations.

PMID- 9567887
TI  - Class 2 division I malocclusion: an orthodontic and porcelain veneer treatment.

PMID- 9567888
TI  - An aesthetic case study.

PMID- 9567889
TI  - A surgeon's diary: the children of Vietnam.

PMID- 9567890
TI  - Facial augmentation with HA. Launching a new industry. Hydroxyapatite.

PMID- 9567891
TI  - Taking responsibility for occlusion.

PMID- 9567892
TI  - Simplified impression-taking technique.

PMID- 9567893
TI  - Temporary cross arch stabilization of edentulous implant patients: the final
      case.

PMID- 9567894
TI  - The walking bleach: 35 years later.

PMID- 9567895
TI  - Suturing techniques for advanced extraction therapy.

PMID- 9567896
TI  - Can your hygienist go bowling between 10 AM and 2 PM?

PMID- 9567897
TI  - Scheduling for success.

PMID- 9567898
TI  - Ten steps to a 'wow' practice.

PMID- 9567900
TI  - Teaching as a tool.

PMID- 9567899
TI  - Increase case acceptance with effective communication skills.

PMID- 9567901
TI  - Learning in dental education.
AB  - Learning in dental education has long been a subject of academic research. There
      are different types of student learning which directly or indirectly contribute
      to the learning outcomes. In this paper, the various classifications of different
      types of learning; superficial, deep, individual, collaborative and resource
      based learning are explored. In order to achieve the learning objectives,
      different teaching methods such as group-work, role-play and problem-based
      learning are employed. The types of resources used in present day teaching are
      diverse and multiple: such as print-based, computer-based technologies and audio
      visual technologies. In order to assess the effectiveness of such teaching,
      different methods of assessment have been adopted for use in higher education. In
      the context of good teaching in higher education, there are a number of
      constraints placed upon the individual and the institution. These constraints are
      discussed and recommendations made whereby they may be overcome.

PMID- 9567902
TI  - X-ray microtomography: 3-dimensional imaging of teeth for computer-assisted
      learning.
AB  - X-ray microtomography (XMT), a miniaturised form of computed tomography, has been
      used to generate 3-dimensional volume data sets of the X-ray absorption of human
      teeth in vitro, with a resolution of approximately 40 microns (cubic voxel
      sidelength). Examples are presented of images relevant to dental morphology,
      cariology, and cavity preparation and restoration. Applications of XMT imaging to
      dental education are discussed in the context of new approaches to visual
      learning through computer-assisted methods.

PMID- 9567903
TI  - The effect of a multimedia interactive tutorial on learning endodontic problem
      solving.
AB  - New technology may create additional opportunities for learning in dental
      education. One of these new features is a multimedia approach, courseware
      combining sound, text, stills and video with interactive learning. A multimedia
      program was developed to train dental students and dental practitioners in
      decision making and problem solving in endodontics. This study compared the
      effects of the multimedia program with a more traditional approach consisting of
      written information, without interaction. 28, 4th-year dental students at the
      University of Kentucky in Lexington, KY, USA were randomly assigned to the
      multimedia or the text-based groups. They were given a written pre-test using 2
      cases of dental pain and were instructed to study independently using either the
      multimedia program (group A) or the written information (group B). No
      restrictions were imposed on the amount of time to be invested, and the total
      study time was recorded for each student. 3 weeks after the pre-test, the
      students completed the post-test. A total of 18 students completed both the pre
      test and the post-test and their scores were included in the final data.
      Statistical analysis of the average scores using paired t-tests revealed no
      significant difference between the performance of the students in either group,
      indicating that the multimedia approach to learning endodontic problem solving
      may successfully replace traditional learning strategies.

PMID- 9567904
TI  - A French dental school programme appraisal by alumni of 5-9 years standing.
AB  - The objective of this study was to analyse the perception of the practical value
      of their training experience for 4 groups of alumni graduated between 1986 and
      1989 at the Faculty of Odontology, University Paris 5. The 240 participants (45%
      response rate) perceived their training to have been adequate with respect to
      procedural activities. On the other hand, the graduates expressed a desire for
      more emphasis in emergencies, interpersonal relationship, office management and
      such clinical topics as fixed prosthodontics, surgery and periodontics. Surveys
      aimed at alumni may be useful for the evaluation of programme results and to
      determine which items should be added or deleted according to either health
      criteria or the conditions of dental practice.

PMID- 9567905
TI  - Teaching as a Tool. Proceedings of the 22nd Meeting of the Association for Dental
      Education in Europe. Utrecht, The Netherlands, 5-7 September 1996. Abstracts.

PMID- 9567906
TI  - The absence of a culture of science in dental education.

PMID- 9567907
TI  - A study of personality factors and interaction in 4th-year dental students and
      their teachers.
AB  - No previous investigation has considered dental student and teaching staff
      opinions on their relationship with each other. In a day when students are
      increasingly asked for feedback on the quality of teaching by staff, such
      investigations are of particular interest. This exploratory study was designed to
      compare the personality characteristics of a clinical year of dental students
      with those of the teaching staff they most frequently encountered, and to
      investigate these factors for possible associations with the quality of perceived
      teaching-learning interaction between the 2 groups. A complete 4th year of dental
      students (n = 87), and those teachers whom they met regularly (n = 80), were
      asked to participate. Subjects completed a form of the Myers-Briggs personality
      questionnaire simplified for use in education, and were asked to assess their
      relationship with persons in the other group. All the students and 75% of the
      staff, after follow-up, returned usable data. There was close similarity between
      staff and student personality profiles, and perception of working relationships
      by both groups was largely independent of personality factors and temperament.
      There were differences in staff perception of their relationship with extrovert
      and introvert students. Students showed minor differences in their perception of
      staff relationships with respect to two other personality factors. These findings
      indicate a substantial similarity between staff and students, and suggest a
      mature and stable relationship between people in the 2 groups.

PMID- 9567908
TI  - Acceptance of psychology teaching in paediatric dentistry by undergraduate dental
      students.
AB  - By means of a questionnaire, 4 cohorts of undergraduate students (n = 144) were
      asked before and after the clinical course in paediatric dentistry about their
      acceptance of the teaching of psychological aspects in dentistry. A generally
      very high interest was found for psychology as well as for child-related
      psychology. The teaching of this topic by means of lectures was thought to be
      useful, but other didactic means were demanded to supplement teaching. For many
      of the aspects taught, more information was requested. Moreover, teaching of
      aspects not taught in the lectures was also requested. The more obvious the
      practical relevance of each topic appeared, the greater was the students'
      interest. Psychology was thought to be useful as an aid to paediatric treatment.
      However, interest dropped after the completion of the paediatric dentistry
      course. It is concluded that undergraduate dental students have no particular
      inclination towards the treatment of children but rather a need for guidelines to
      avoid potential problems in dealing with this demanding group of patients.

PMID- 9567909
TI  - Problem solving and problem-solving education in dentistry.
AB  - Academic education in dentistry should lead to the capability to solve complex
      open problems. The student entering university is only familiar with closed
      problems. Research into the making of a medical diagnosis has shown that novices
      do so differently than experts. These research results are summarised and are
      presumed to be transferable to dental diagnosing and treatment planning. Examples
      of this transfer are given. Until 1 or 2 decades ago, education in problem
      solving was done only by extensive teacher-student interaction in clinical and
      scientific work. Presently, this is no longer adequate because of reduction of
      curriculum time for these activities. Therefore other methods have been developed
      in many places. These methods include the use of a problem-solving model
      (heuristic). Based on models in the literature, 3 new models are presented. These
      are intended for novices that solve a dentally relevant open problem in basic
      sciences, for novices that solve a clinical dental problem, and for more expert
      students that solve such a problem. Diagrams and examples are given.

PMID- 9567910
TI  - Student and staff opinion of electronic capture of data related to clinical
      activity.
AB  - OBJECTIVE: To seek the opinion of staff and students of a new electronic method
      for collection of data related to student clinical activity. DESIGN:
      Questionnaire survey. SETTING: Staff and students in the Department of Child
      Dental Health, Dental School, Cardiff, and staff in the Community Dental Service
      who undertake clinical supervision. METHOD: A questionnaire was circulated to all
      2nd and 3rd clinical year dental undergraduate students seeking their opinion on
      a range of issues associated with the recently introduced bar code system of data
      gathering of their clinical activity and achievement. A similar questionnaire was
      circulated to staff who have responsibility for clinical supervision of these
      students. RESULTS: A total of 102 replies were received. With the exception of 2
      aspects, there was no disagreement between staff and students. An overall
      majority preferred the use of bar codes to other methods of data collection; bar
      codes were perceived to be more accurate and reliable than other methods;
      students were satisfied with the method of quality assessment; staff were
      dissatisfied (P < 0.05). Staff were strongly in favour of extension of the use of
      bar codes to other clinics, whereas students were less strongly in favour (P <
      0.001); there was little enthusiasm to extend bar codes for recording attendance
      at lectures, seminars and other such activity. CONCLUSION: The new system has
      been accepted by staff and students alike. It has proven to be satisfactory for
      its intended purpose. As a result of this survey, minor adjustments to procedures
      will take place, and the method of assessment of clinical work will be
      reconsidered.

PMID- 9567911
TI  - The Baltic dental programme at the Faculty of Dentistry of The Karolinska
      Institute: first evaluation.
AB  - In 1992, The Faculty of Dentistry of The Karolinska Institute (KI) introduced a
      dental undergraduate programme specifically for Baltic students. Initiative for
      this programme came from both the Ministries of Health in Estonia and Latvia and
      a Member's Bill in the Swedish Committee for Foreign Affairs. The first 10
      students were admitted in January 1992, and in 1994, a further 8 students were
      accepted. The main objective is to train Baltic students according to the
      Scandinavian model of dental education, in order to facilitate a positive
      development in dentistry in these countries. Candidates for the programme, dental
      students in Latvia or Estonia who had completed several preclinical years, were
      interviewed and tested in their home countries by a Swedish Admissions Committee.
      The curriculum comprises 7 semesters at the School of Dentistry, and includes
      complementary courses in basic science, preventive dentistry, and theoretical and
      practical courses in all fields of clinical dentistry. The students work with
      increasing independence, treating patients with a great variety of oral diseases
      and from different age groups. A course in Informatics is central and forms a
      base for a research-based assignment in collaboration with the respective home
      universities. The Baltic Programme is the first time KI has designed and
      implemented a specially tailored dental undergraduate curriculum in English for a
      selected group of foreign undergraduates. The students have proved to be
      ambitious and industrious, with very high academic standards. Their results in
      the written examinations were equal to or better than those of the home students.
      Of the 9 students who to date have completed the course, all are working as
      dentists in their respective countries and 6 are associated with their
      university.

PMID- 9567912
TI  - Undergraduate training in the European Union. Convergence or divergence?
AB  - A survey of dental schools in the European Union was carried out for two main
      reasons. Firstly to promote the exchange of information in respect of curriculum
      objectives in the different countries and secondly to ascertain the differences
      in the interpretation of the 1978 EU sectoral directives for dental education and
      training. Out of 127 schools, only 30 responded, yet the information provided is
      of considerable importance. It demonstrates wide divergence in the interpretation
      of the 1978 Directives and methods of assessment of clinical competence. There is
      a considerable difference throughout Europe in hours devoted to the various
      subjects included in the Dental Directives. There is little evidence of
      convergence in methods of assessment or quality assurance. The survey
      demonstrates the difference in resources, levels of staff, availability of
      clinical training places, output in research and patient treatments throughout
      the European Union. The results question the effectiveness of the 1978 Dental
      Directives in promoting convergence of standards. As there is free movement of
      dentists throughout the European Union, it is concluded that a different approach
      may be necessary to ensure that all European Union dental graduates achieve
      comparable standards in their education and training.

PMID- 9567913
TI  - Information technology in oral health education.

PMID- 9567914
TI  - Curricular adaptations towards problem-based learning in dental education.

PMID- 9567915
TI  - A new admission procedure to dental education at The Karolinska Institute. An
      initial evaluation.
AB  - This study compares the performance to date of dental under-graduates selected by
      a new, individual admissions procedure, and those admitted by the traditional
      centralised system (control groups). Admission to all full-time tertiary study in
      Sweden was centralised and administered by special national units until 1993,
      following which the universities were allowed to adopt their own admission
      system. The Dental School at The Karolinska Institute in 1993 introduced an
      individualised selection system, initially for one-third and subsequently for 60%
      of the freshmen intake, the remaining places being reserved for students applying
      through the national admissions centre. The main objective of the new selection
      procedure is to seek out highly motivated students (less likely to drop-out) with
      general competence, high academic achievement, and personal attributes considered
      important in a health professional. An Admissions Committee (AC) comprising seven
      faculty members, was appointed by the Vice-Chancellor, for the new system which
      has been used unaltered since 1993. In the first stage applicants with the
      highest academic grades are selected in descending order. In the second stage,
      the prospective students spend a day at The Dental School writing separate
      assignments, which are assessed by the AC according to defined criteria.
      Applicants who do well in the written assessment proceed to the third stage in
      which each applicant is interviewed by two AC members on separate occasions. In
      the final selection procedure, the AC considers the combined merits of all the
      interviewed applicants. Analysis of the first three intakes discloses few or no
      drop-outs among AC-selected undergraduates. In three major integrated
      examinations, designed to disclose not only factual knowledge but also
      comprehension and maturity and as such reflect clinical conditions, their
      performance is as good as or better than the control groups.

PMID- 9567916
TI  - Clinical guidelines and self-assessment in dental education.
AB  - This paper describes an educational programme where clinical guidelines are used
      in dental education and assesses the value of these guidelines as perceived by
      undergraduate students. It presents a comparison of students' own assessments of
      their performance with those of their instructors, according to such guidelines.
      The educational programme at the Faculty of Odontology, Lund University, is
      described through 3 main principles: problem-based learning, adoption of a
      holistic attitude to patient care and the promotion of oral health. The dental
      curriculum occupies 5 years comprising 10 semesters. 41, 5th semester students
      (16 male and 25 female) participated in the study. Students were introduced to
      guidelines in group discussions at the beginning of the semester. At the
      completion of a patient's planned course of treatment, the outcome was formally
      assessed both by students and clinical instructors. Performance was scored in
      various categories as "excellent", "acceptable" or "unacceptable" according to
      the standards defined. A total of 1373 scores were made by both students and
      instructors. 88% cent of students used the guidelines often or almost always and
      found them useful. Overall, no students received an "unacceptable" score and 40%
      of students achieved a score of "excellent". Female students tended towards a
      higher score, but this was not significant. Instructors' and students' scores
      agreed in almost 90% of instances. Students under-scored their performance more
      frequently than they over-scored it. It appears that the use of clinical
      guidelines may encourage an increased awareness of the decision-making processes
      involved in clinical practice, but it must be acknowledged that these guidelines
      are complex both in derivation and application.

PMID- 9567917
TI  - Khmer dental and medical students' knowledge about the betel quid chewing habit
      in Cambodia.
AB  - 95 of 144 questionnaires submitted by volunteer Khmer medical and dental students
      on the betel quid chewing habit in Cambodia were evaluated (58 medical, 37
      dental). Questions related to the composition of the betel quid, the
      physiological and oral effects as well as traditional and sociological aspects.
      Statistical tests showed that there were differences between dental and medical
      students, particularly relating to the knowledge about oral effects. While 81.1%
      of dental students knew that betel quid chewing causes oral cancer, only 31.0% of
      the medical students were adequately informed. Similarly, 51.4% of the dental
      students knew about the relation between betel quid chewing and submucous
      fibrosis compared to 8.6% of the medical students (P < 0.001). In contrast, only
      18.9% of the dental students thought that betel quid chewing strengthens the gum,
      while 56.9% of the medical students believed that betel quid chewing would have
      this effect (P < 0.001). The answers also showed that students do not indulge in
      the betel quid habit. The decline of the betel quid chewing habit was also
      indicated by the fact that while 5.3% of students had parents chewing betel quid,
      in contrast 40% of students reported grandparents with this habit. There are
      deficiencies of knowledge about the most important effects of betel quid chewing,
      particularly in medical students. Since both medical and dental students will in
      their future professional life have an enormous impact on health and health
      education, it seems justified that the dental and medical curricula should focus
      on these traditional habits. Proper health education starting in the dental and
      medical school is warranted in Cambodia and probably also in other South and
      Southeast Asian countries where the betel quid chewing habit is prevalent so as
      ultimately to improve public knowledge on the oral and other effects of this
      habit.

PMID- 9567918
TI  - Undergraduate orthodontics in Belfast: 12 years on.
AB  - The British and European Community recommendations for teaching orthodontics in
      the undergraduate curriculum from 1963 up to the present day are reviewed. 12
      years experience of the course introduced in Belfast in 1984 is reviewed and some
      of the difficulties are identified. Modifications in the course to meet these
      difficulties are described.

PMID- 9567919
TI  - A study to determine if changes to an undergraduate orthodontic course improved
      course quality and student satisfaction.
AB  - A study was carried out to determine if changes to the undergraduate orthodontic
      course at Leeds Dental Institute resulted in increased student satisfaction. The
      study was based on a questionnaire distributed to dental students comprising
      statements related to the undergraduate orthodontic course. Questionnaires were
      distributed in 1993 and 1995 to 2 groups of 4th year undergraduate dental
      students at the same stage of their course on both occasions. Questions were in
      the form of 16 statements with which students expressed a level of agreement,
      ranging from strongly agree to strongly disagree. The numbers of responses at
      each level of agreement were compared between the 2 groups. Statistical
      differences were determined using a Mann Whitney-U test. 8 of the 16 statements
      had more favourable responses in 1995 than in 1993. No statement received a less
      favourable response in 1995 than in 1993. It is concluded that changes in the
      undergraduate orthodontic course at Leeds Dental Institute aimed at increased
      problem-based learning and clinician-led tutorials, have resulted in improved
      student satisfaction with the teaching.

PMID- 9567920
TI  - Communication skills training courses in dental education.
AB  - In this article, some reasons for teaching communication skills in dental schools
      are discussed. An overview of 3 courses at the Amsterdam dental school is
      presented, along with the results of a student evaluation. Students evaluated
      these courses as useful and relevant for dental practice. It is concluded that
      this is especially so when the students recognize direct applicability of the
      courses to dental practice.

PMID- 9567921
TI  - The development of the periodontium--a largely ectomesenchymally derived unit.

PMID- 9567922
TI  - The periodontal ligament: a unique, multifunctional connective tissue.

PMID- 9567923
TI  - Dental cementum: the dynamic tissue covering of the root.

PMID- 9567924
TI  - Alveolar bone and the alveolar process: the socket that is never stable.

PMID- 9567925
TI  - The gingival tissues: the architecture of periodontal protection.

PMID- 9567926
TI  - Apical periodontitis: a dynamic encounter between root canal infection and host
      response.

PMID- 9567927
TI  - Diagnostic techniques in periodontology: a historical review.

PMID- 9567928
TI  - Histology of the periodontal lesion: implications for diagnosis.

PMID- 9567929
TI  - Clinical evaluation of periodontal diseases.

PMID- 9567930
TI  - Radiographic diagnosis in periodontics.

PMID- 9567931
TI  - The laboratory diagnosis of periodontal infections.

PMID- 9567932
TI  - Diagnosis of periodontal disease based on analysis of the host response.

PMID- 9567933
TI  - Issues in assessment of diagnostic tests and risk for periodontal diseases.

PMID- 9567934
TI  - Pharmacokinetic principles of antimicrobial therapy.

PMID- 9567935
TI  - Selected antimicrobial agents: mechanisms of action, side effects and drug
      interactions.

PMID- 9567936
TI  - Evidence versus empiricism: rational use of systemic antimicrobial agents for
      treatment of periodontitis.

PMID- 9567937
TI  - Systemic antibiotic therapy in periodontics.

PMID- 9567938
TI  - The acquisition of antibiotic resistance in the periodontal microflora.

PMID- 9567939
TI  - Antifungal therapy in the oral cavity.

PMID- 9567940
TI  - Antibiotic prophylaxis and the medically compromised patient.

PMID- 9567941
TI  - Local delivery of antimicrobial agents in the periodontal pocket.

PMID- 9567942
TI  - Current patterns of oral hygiene product use and practices.

PMID- 9567943
TI  - Behavioral research related to oral hygiene practices: a new century model of
      oral health promotion.

PMID- 9567944
TI  - Monitoring the efficacy of plaque control methods.

PMID- 9567945
TI  - Supragingival dental plaque in the etiology of oral diseases.

PMID- 9567946
TI  - The expected effect on oral health of dental plaque control through mechanical
      removal.

PMID- 9567947
TI  - Chemical agents: plaque control, calculus reduction and treatment of dentinal
      hypersensitivity.

PMID- 9567949
TI  - The role of dental professionals and the patient in plaque control.

PMID- 9567948
TI  - Chemical agents to prevent and regulate plaque development.

PMID- 9567950
TI  - The effect of restorative and prosthetic materials on dental plaque.

PMID- 9567951
TI  - Supragingival dental calculus.

PMID- 9567952
TI  - The development of periodontal plastic surgery.

PMID- 9567953
TI  - The aesthetic smile: diagnosis and treatment.

PMID- 9567955
TI  - Double pedicle flap--predictability and aesthetics using connective tissue.

PMID- 9567954
TI  - The restorative-periodontal interface: biological parameters.

PMID- 9567956
TI  - Guided tissue regeneration in gingival recessions.

PMID- 9567957
TI  - A perspective on the future of periodontal microsurgery.

PMID- 9567958
TI  - Progress in gingival papilla reconstruction.

PMID- 9567959
TI  - Alveolar ridge preservation and reconstruction.

PMID- 9567960
TI  - Aesthetics and implant dentistry.

PMID- 9567961
TI  - Plastic surgery techniques applicable to periodontal flap surgery.

PMID- 9567962
TI  - Suturing techniques for periodontal plastic surgery.

PMID- 9567963
TI  - The pathogenesis of human periodontitis: an introduction.

PMID- 9567964
TI  - The microbial challenge in periodontitis.

PMID- 9567965
TI  - The host response to the microbial challenge in periodontitis: assembling the
      players.

PMID- 9567966
TI  - The acute inflammatory response and the role of phagocytic cells in periodontal
      health and disease.

PMID- 9567967
TI  - Induction of the immune response to periodontopathic bacteria and its role in the
      pathogenesis of periodontitis.

PMID- 9567968
TI  - Cytokines and prostaglandins in immune homeostasis and tissue destruction in
      periodontal disease.

PMID- 9567969
TI  - Mechanisms of connective tissue matrix destruction in periodontitis.

PMID- 9567970
TI  - Mechanisms of alveolar bone destruction in periodontitis.

PMID- 9567971
TI  - Influence of risk factors on the pathogenesis of periodontitis.

PMID- 9567972
TI  - Genetic factors in the pathogenesis of periodontitis.

PMID- 9567973
TI  - Advances in the pathogenesis of periodontitis: summary of developments, clinical
      implications and future directions.

PMID- 9567974
TI  - The rationale for periodontal therapy.

PMID- 9567975
TI  - Clinical and microbiological response to nonsurgical mechanical periodontal
      therapy.

PMID- 9567976
TI  - Clinical considerations in nonsurgical mechanical therapy.

PMID- 9567978
TI  - Conventional surgical procedures.

PMID- 9567977
TI  - Nonsurgical chemical periodontal therapy.

PMID- 9567979
TI  - Management of furcation involvement.

PMID- 9567980
TI  - Periodontal plastic and mucogingival surgery.

PMID- 9567981
TI  - Occlusal considerations in periodontology.

PMID- 9567982
TI  - Periodontal considerations in prosthetic dentistry.

PMID- 9567983
TI  - Orthodontics and periodontal therapy.

PMID- 9567984
TI  - Lasers in periodontal therapy.

PMID- 9567986
TI  - Supportive periodontal treatment.

PMID- 9567985
TI  - Periodontal management of the medically compromised patient.

PMID- 9567987
TI  - Supportive periodontal treatment introduction--definition, extent of need,
      therapeutic objectives, frequency and efficacy.

PMID- 9567988
TI  - Compliance and its role in periodontal therapy.

PMID- 9567989
TI  - A typical supportive periodontal treatment visit for patients with periodontal
      disease.

PMID- 9567990
TI  - A typical maintenance visit for patients with dental implants.

PMID- 9567991
TI  - Manual periodontal probing in supportive periodontal treatment.

PMID- 9567992
TI  - Computerized periodontal probing.

PMID- 9567993
TI  - Monitoring disease during supportive periodontal treatment by bleeding on
      probing.

PMID- 9567994
TI  - In-office diagnostic tests and their role in supportive periodontal treatment.

PMID- 9567995
TI  - Microbial analysis in supportive periodontal treatment.

PMID- 9567996
TI  - Monitoring disease around dental implants during supportive periodontal
      treatment.

PMID- 9567997
TI  - The use of hand instruments in supportive periodontal treatment.

PMID- 9567998
TI  - Ultrasonic instruments and antimicrobial agents in supportive periodontal
      treatment and retreatment of recurrent or refractory periodontitis.

PMID- 9567999
TI  - Retreatment for patients with inflammatory periodontal disease.

PMID- 9568000
TI  - Retreatment for patients with inflammatory periodontal disease.

PMID- 9568001
TI  - Retreatment for patients with inflammatory periodontal disease.

PMID- 9568002
TI  - Retreatment for patients with inflammatory periodontal disease.

PMID- 9568003
TI  - Retreatment for patients with inflammatory periodontal disease.

PMID- 9568004
TI  - The role of tetracycline--impregnated fibers in retreatment.

PMID- 9568005
TI  - Digestive Disease Week and the 99th annual meeting of the American
      Gastroenterological Association. New Orleans, Louisiana, USA. May 16-22, 1998.
      Abstracts.

PMID- 9568006
TI  - American Urological Association 93rd annual meeting. San Diego, California, USA.
      May 30-June 4, 1998. Abstracts.

PMID- 9568007
TI  - American Academy of Neurology 50th annual meeting. Minneapolis, Minnesota, USA.
      April 1998. Abstracts.

PMID- 9568008
TI  - A review of violence statistics among children and adolescents in the United
      States.
AB  - This article defines the violence and data on juvenile homicide rates and arrest
      rates for violent crimes in the United States. Mortality data associated with
      juvenile violence from the United States and similar data from other industrial
      countries are also compared.

PMID- 9568009
TI  - Theoretical frameworks. Developmental psychopathology, the public health approach
      to violence, and the cycle of violence.
AB  - In many disciplines, there are applications of theory to provide strategies for
      research and practice. But, at this point in time, given the complex nature of
      violence, few existing theories effectively address all important variables. In
      order to overcome deficiencies in violence theory development, it will be
      necessary for violence researchers and practitioners to better define the concept
      of violence, improve research designs and program evaluations, and make
      multidisciplinary collaboration a priority.

PMID- 9568010
TI  - Risk and resiliency factors for violence.
AB  - Research on human resiliency in the face of adversity has gained widespread
      currency in the study of the developmental outcomes for children exposed to
      multiple risk factors. This article reviews several of these studies from a
      multilevel perspective, with a view to documenting their contributions and
      limitations and what needs to be done in the future.

PMID- 9568011
TI  - Violence and associated high-risk health behavior in adolescents. Substance
      abuse, sexually transmitted diseases, and pregnancy of adolescents.
AB  - The intricate relationship between the social and health behaviors of persons of
      all ages has long been described. In adolescent health care, the risk-taking
      behaviors that are recognized in the areas of sexuality, drug and alcohol abuse,
      and violence need to be addressed. This article discusses adolescent risk
      behaviors and their relationships to violence. Health care providers need to
      consider these risk behaviors as they care for adolescents.

PMID- 9568012
TI  - Media violence.
AB  - American media are the most violent in the world, and American society is now
      paying a high price in terms of real life violence. Research has confirmed that
      mass media violence contributes to aggressive behavior, fear, and desensitization
      of violence. Television, movies, music videos, computer/video games are pervasive
      media and represent important influences on children and adolescents. Portraying
      rewards and punishments and showing the consequences of violence are probably the
      two most essential contextual factors for viewers as they interpret the meaning
      of what they are viewing on television. Public health efforts have emphasized
      public education, media literacy campaign for children and parents, and an
      increased use of technology to prevent access to certain harmful medial
      materials.

PMID- 9568013
TI  - Consequences of violence. Premature death, violence recidivism, and violent
      criminality.
AB  - The burden of violence is born disproportionately by the youngest of our country.
      In this article, three important aspects of violence are discussed: premature
      death, violence recidivism, and violent criminality. The author emphasizes the
      role of the pediatrician in preventing these consequences.

PMID- 9568014
TI  - Post-traumatic stress disorder in children and adolescents exposed to violence.
AB  - The common biopsychosocial sequelae of violence exposures are reviewed, with a
      focus on post-traumatic stress disorder in developmental, clinical, and familial
      contexts. Challenges to assessment are reviewed, and implications for prevention
      and treatment are presented. Pediatricians have an essential role to play in
      secondary and tertiary prevention through the use of anticipatory guidance and
      victimization as a marker of developmental risk.

PMID- 9568015
TI  - The impact of children witnessing violence.
AB  - Over the past decade, Americans have recognized that violence has deeply
      permeated the lives of the most vulnerable among us--children. There is great
      concern over the effect these terrible experiences will have on present and
      future generations. It has also awakened the collective consciousness of our
      society that the impact of violence extends well beyond the child who is
      physically victimized to other larger groups of children such as those who
      witness these events. This article reviews the impact violence has on children.

PMID- 9568016
TI  - Adolescent suicide.
AB  - This article reviews the origin of youth suicide. Theoretic suicide risk factors
      and empirically observed suicide risk factors are discussed along with proposed
      resiliency factors that prevent suicide. Finally, suicide prevention and
      intervention strategies are covered, and a call for better studies on suicide
      prevention is heralded.

PMID- 9568017
TI  - Dating violence.
AB  - Dating violence presents many challenges to pediatric health care providers. It
      spans an age range from early high school to early adult years. Prevalence of
      dating violence appears to be greater than for violence among married couples. In
      addition, both males and females appear to be at risk for perpetration and
      victimization. Therefore, physicians and other health care providers need to
      screen all adolescent and young adult patients for dating violence. Primary
      prevention at the community level is also an important task to stem the tide of
      dating violence.

PMID- 9568018
TI  - Psychosocial aspects of child abuse for primary care pediatricians.
AB  - Childhood is an image that advertisers use to conjure up feelings of care-free
      innocence. Society frequently calls for protecting our children and creating
      strong, healthy families. Yet thousands of children experience violence on a
      regular basis, and their lives are irretrievably altered. For these children, the
      sites of violence and not war-torn villages or crime-ridden streets but their own
      homes. This article provides primary care physicians with basic information about
      the psychosocial aspects of recognition and prevention of child abuse.

PMID- 9568019
TI  - Corporal punishment.
AB  - Pediatricians differ on the optimal ways to discipline children. The major
      controversy surrounds the use of corporal punishment. In an effort to resolve
      this controversy, the American Academy of Pediatrics (AAP) cosponsored a
      conference entitled "The Short and Long-Term Consequences of Corporal Punishment"
      in February 1996. This article reviews scientific literature on corporal
      punishment and summarizes the proceedings from the conference. The authors
      conclude that, although the research data are inadequate to resolve the
      controversy, there are areas of consensus. Practitioners should assess the
      spanking practices of the parent they see and counsel parents to avoid those that
      are, by AAP consensus, dangerous, ineffective, or abusive.

PMID- 9568020
TI  - Violence against children and adolescents. International perspectives.
AB  - Selected topics of violence against children and adolescents that occur in
      countries outside of the United States are discussed. Focus is given to middle
      income and low-income countries and emphasis is placed on the epidemiology of
      this pressing public health problem, particularly on conditions that are peculiar
      to children and adolescents in international settings, such as female genital
      mutilations, wars, displacements, and land mines. The discussion of child
      maltreatment is presented in the context of child rearing and discipline in
      different cultures. Recommendations for action and violence prevention are
      offered in the light of vast cultural differences.

PMID- 9568021
TI  - Prevention of firearm-related injuries and deaths among youth. A product-oriented
      approach.
AB  - Firearm-related injuries are the second leading cause of death in youth. A
      product-oriented approach, focusing on the gun, may be an efficient and effective
      strategy to reduce firearm-related injuries and death. Such an approach includes
      decreasing the number of guns in the environment and modifying the gun to reduce
      it potential for harm. As with efforts to reduce childhood injuries from motor
      vehicle crashes and poisonings, pediatric health professionals can assume a
      leadership role in preventing firearm-related injuries and death in youth.

PMID- 9568022
TI  - Violence anticipatory guidance.
AB  - A series of brief office counseling interventions for the prevention and
      treatment of violence is reviewed in this article. Primary prevention strategies
      throughout the pediatric age span cover topics from gun storage to nonviolent
      handling of a potential street fight. Secondary prevention strategies deal with
      patients who have been injured by violence or patients who engage in street
      violence, weapon carrying, or dating violence.

PMID- 9568023
TI  - Impact of violence and the emergency department response to victims and
      perpetrator. Issues and protocols.
AB  - Research on the current epidemic of violence and its victims is limited. In the
      past decade, considerable attention has been focused in the area of domestic
      violence. Comprehensive emergency department (ED) domestic violence protocols
      have been developed and evaluated that address identification, treatment, safety
      issues, legal reporting statutes, and medical and psychosocial interventions.
      This article focuses on victims, perpetrators, and the occurrence of violence in
      the ED and describes issues and strategies for identification, intervention, and
      documentation.

PMID- 9568025
TI  - Virus-induced host gene shutoff in animals and plants.

PMID- 9568024
TI  - Successful approaches to community violence intervention and prevention.
AB  - The field of injury prevention and control is diverse, cross-cutting, and has
      attracted the efforts of individuals from multiple disciplines. Many types of
      interventions have been applied in the area on intentional injury, specifically
      interpersonal violence. The results have been variable with few projects
      demonstrating scientific efficacy. Among the acknowledged stumbling blocks have
      been issues of project design, and deficiencies in the incorporation of
      communities into project development and implementation. This article discusses
      those elements that are critical to the creation of any community-based violence
      prevention intervention and offers guidelines for establishing a project's
      community context.

PMID- 9568026
TI  - Anti-HIV effects of HIV vectors.
AB  - We have recently developed an HIV-1 packaging cell line, psi 422, as an improved
      tool for anti-HIV gene therapy. After stable transfection with an HIV-1 or HIV-2
      vector, psi 422 has been shown to synthesize virions able to transduce CD4+ T
      cells and macrophages. We now report that HIV vectors per se, in the absence of
      antiviral genes, inhibit HIV infection of transduced cells. This antiviral effect
      was shown to be due, at least in part, to a TAR and RRE decoy effect. These data
      highlight further advantages of HIV-derived gene delivery systems for HIV
      therapy, in addition to CD4 cell targeting and the ability to transduce
      nondividing cells.

PMID- 9568027
TI  - Type specific and genotype cross reactive B epitopes of the L1 protein of HPV16
      defined by a panel of monoclonal antibodies.
AB  - Mouse monoclonal antibodies (mAbs) were raised against the major capsid protein,
      L1, of human papillomavirus type 16 (HPV16), produced in Escherichia coli with
      the expression plasmid pTrcL1. Epitope specificity could be assigned to 11 of
      these 12 antibodies using a series of linear peptides and fusion proteins from
      HPV16. One mAb (MC53) recognized a novel linear epitope that appears to be unique
      to the HPV16 genotype. A further 11 mAbs were characterized as recognizing novel
      and previously defined linear and conformational epitopes shared among more than
      one HPV genotype. The apparently genotype specific mAb could be useful for the
      development of diagnostic tests for vegetative virus infection in clinical
      specimens.

PMID- 9568028
TI  - Inhibition of Friend virus replication by a compound that reacts with the
      nucleocapsid zinc finger: anti-retroviral effect demonstrated in vivo.
AB  - The zinc finger structure that is found in the nucleocapsid protein of nearly all
      retroviruses has been proposed as a target for antiviral therapy. Since compounds
      that chemically attack the cysteines of the finger have been shown to inactivate
      both human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MuLV)
      in vitro, 14 of these compounds were tested in an MuLV-induced Friend disease
      model to assess their ability to inhibit retroviral replication in vivo. Of the
      14 compounds tested, only Aldrithiol-2 clearly exhibited anti-retroviral activity
      as measured indirectly by the delay of Friend disease onset (P < 0.05). These
      results were confirmed by quantitative competitive polymerase chain reaction
      studies which monitored viral spread by measuring the level of viral DNA in the
      peripheral blood mononuclear cells of treated mice. Comparison of treated mice
      with untreated mice revealed that Aldrithiol-2 produced a greater than 2-log
      reduction in virus levels. These results functionally demonstrate that a zinc
      finger-attacking compound can inhibit viral replication in vivo. Since only 1 of
      the 14 compounds studied was effective, this study also shows the importance of
      in vivo testing of these types of antiviral compounds in an animal model. Given
      the strict conservation of the metal-coordinating cysteine structure within HIV-1
      and MuLV zinc fingers, our results support the proposal that anti-retroviral
      drugs which target the nucleocapsid zinc finger may be clinically useful against
      HIV-1.

PMID- 9568029
TI  - Structural homology of the central conserved region of the attachment protein G
      of respiratory syncytial virus with the fourth subdomain of 55-kDa tumor necrosis
      factor receptor.
AB  - The attachment protein G of respiratory syncytial virus (RSV) has a modular
      architecture. The ectodomain of the protein comprises a small folded conserved
      region which is bounded by two mucin-like regions. In this study, a sequence and
      structural homology is described between this central conserved region of RSV-G
      and the fourth subdomain of the 55-kDa tumor necrosis factor receptor (TNFr). The
      three-dimensional structures of RSV-G and human TNFr were previously determined
      with NMR spectroscopy and X-ray crystallography, respectively. The C-terminal
      part of both subdomains fold into a cystine noose connected by two cystine
      bridges with the same spacing between cysteine residues and the same topology.
      Although a general structural similarity is observed, there are differences in
      secondary structure and other structural features. Molecular Dynamics
      calculations show that the BRSV-G NMR structure of the cystine noose is stable
      and that the TNFr crystal structure of the cystine noose drifts towards the BRSV
      G NMR structure in the simulated solution environment. By homology modelling a
      model was built for the unresolved N-terminal part of the central conserved
      region of RSV-G. The functions for both protein domains are not known but the
      structural similarity of both protein domains suggests a similar function.
      Although the homology suggests that the cystine noose of RSV-G may interfere with
      the antiviral and apoptotic effect of TNF, the biological activity remains to be
      proven.

PMID- 9568030
TI  - Two regions of simian virus 40 large T-antigen independently extend the life span
      of primary C57BL/6 mouse embryo fibroblasts and cooperate in immortalization.
AB  - Expression of the SV40 large T-antigen allows primary cells to escape senescence
      and thereby become immortalized. Immortalization occurs in two steps, extension
      of life span and acquisition of unlimited cell division potential. By following
      the increase in expression of a senescence-associated marker with increased cell
      passage, we show that C57Bl/6 mouse embryo fibroblast (B6MEF) cultures senesce by
      passage 4. Thus, the development of colonies from cultures transfected with T
      antigen expressing constructs indicates extension of life span. Two T-antigen
      regions independently extended the life span of B6MEF. Expression of either a T
      antigen consisting of amino acids 1-147 (T1-147) or a T-antigen consisting of
      amino acids 251-708 (T251-708) resulted in colony development. However, the
      colonies expressing these truncated T-antigens could not be expanded into cell
      lines efficiently. In contrast, coexpression of T1-147 and T251-708 produced
      colonies that could be expanded into cell lines as efficiently as could colonies
      expressing full-length T-antigen. Thus, the two regions of T-antigen contain
      analogous activities that are sufficient to extend cell life span; they cooperate
      to immortalize primary B6MEF; and they act in trans, indicating that the
      functions involved are independent.

PMID- 9568031
TI  - Antibodies directed to envelope proteins of hepatitis C virus outside of
      hypervariable region 1.
AB  - The relatively high variability of the hepatitis C virus (HCV) envelope proteins
      E1 and E2 suggests that parts of these proteins other than the hypervariable
      region 1 (HVR1) might be involved in the induction of virus neutralizing
      antibodies. To test this hypothesis, two HCV proteins, pE1 and pE2 delta, were
      generated by in vitro translation. They represent amino acids 174-337 of E1 and
      411-688 of E2, respectively, of isolate HCV-AD78; the protein pE2 delta contained
      no HVR1. As a control, protein pG.HVR1, which represents amino acids 384-410 of
      HVR1 of isolate HCV-AD78, was expressed separately. These three proteins were
      used in an immunoprecipitation assay to detect the presence of antiviral
      antibodies in sera of patients infected with the same isolate of HCV (HCV-AD78).
      Sera were obtained 4-8 months postinfection from patients who later resolved an
      acute infection or developed chronic liver disease. A high prevalence of
      antibodies (up to 85.7%) against pE1 and pE2 delta could be detected in both
      groups of patients, suggesting that these forms of the HCV envelope proteins
      contain B-cell epitopes. The antibody responses against proteins pE1 and pE2
      delta did not differ significantly between patients with resolving or chronic
      infection, whereas antibodies against protein pG.HVR1 were associated with
      resolution of infection. Rabbit antisera raised against pE1 and pE2 delta were
      tested for their ability to neutralize the binding of HCV to susceptible cells in
      tissue cultures. The results suggested that although a few B-cell epitopes
      outside of HVR1 can induce virus neutralizing antibodies, these antibodies are
      probably not associated with the resolution of infection.

PMID- 9568032
TI  - Mechanisms of replication-deficient vaccinia virus/T7 RNA polymerase hybrid
      expression: effect of T7 RNA polymerase levels and alpha-amanitin.
AB  - Components of the eukaryotic vaccinia virus/T7 RNA polymerase hybrid expression
      system were assessed using recombinant and nonrecombinant forms of modified
      vaccinia Ankara (MVA), a replication-deficient vaccinia virus strain. Recombinant
      MVA virus expressing T7 RNA polymerase (Wyatt, L. S., Moss, B., and Rozenblatt,
      S. (1995). Virology 210, 202-205) stimulated high levels of expression from a T7
      promoter-chloramphenicol acetyltransferase (CAT) reporter. Most, but not all, of
      the virally induced expression was T7 RNA polymerase and T7 promoter dependent,
      with no viral enhancement of translation of T7 transcripts. The efficacy of
      supplying T7 RNA polymerase expression from nonviral sources was evaluated using
      a self-amplifying T7 RNA polymerase autogene or an inducible T7 RNA polymerase
      expression vector. The latter modes yielded CAT activity dependent on T7 RNA
      polymerase expression; however, expression required viral factors independent of
      T7 RNA polymerase and did not reach that attained using the recombinant virus. In
      further experiments, MVA-induced T7 RNA polymerase expression was upregulated by
      alpha-amanitin, an inhibitor of eukaryotic polymerases. This indicates that
      MVA/T7 RNA polymerase hybrid expression may be rendered still more efficient by
      ameliorating transcriptional interference due to an alpha-amanitin-sensitive
      eukaryotic factor(s).

PMID- 9568033
TI  - The short Sendai virus leader region controls induction of programmed cell death.
AB  - The replication of nonsegmented minus-strand RNA genomes, like that of Sendai
      paramyxovirus (SeV), are controlled by the short leader regions present at each
      end of the linear genomes and antigenomes; the left and right promoters (PL and
      PR), respectively. Wild-type SeV is highly cytopathic in cell culture, because it
      induces programmed cell death (PCD). We have found that a recombinant SeV
      (rSeVGP42), in which the first 42 nt of le+ sequences at PL were replaced with
      the equivalent sequences of PR, and which produces infectious virus in amounts
      comparable to wild type, does not kill cells. Further, the increasing replacement
      of the terminal le+ sequences at PL with le- sequences led to a decreasing
      fraction of infected cells being apoptotic. This property (PCD-), moreover, is
      dominant in cells co-infected with SeVwt and rSeVGP42, and the mutant virus
      therefore appears to have gained a function which prevents PCD induced by SeVwt.
      Even though this virus has not been selected for naturally, it excludes SeVwt
      during co-infections of cultured cells or embryonated chicken eggs. The
      noncytopathic nature of cells infected or co-infected with rSeVGP42 leads
      automatically to stable, persistent infections. The mutation in rSeVGP42 is not
      in the protein coding regions of the viral genome, but in the 55-nt-long leader
      region which controls antigenome synthesis from genome templates. The SeV leader
      regions, which are expressed as short RNAs, thus appear to control the induction
      of PCD.

PMID- 9568034
TI  - Transposon-mediated random insertions and site-directed mutagenesis prevent the
      trafficking of a mouse mammary tumor virus superantigen.
AB  - Mouse mammary tumor viruses (MMTVs) encode superantigens (Sags) which are
      critical to the life cycle of infectious virus and can mediate extensive deletion
      of T lymphocytes when expressed by endogenous proviruses. Little is known about
      the structure, intracellular trafficking, or nature of Sag association with major
      histocompatibility (MHC) class II products. In order to gain a better
      understanding of Sag structure-function relationships, we extensively mutagenized
      this type II glycoprotein using two different approaches: transposon-mediated
      random in-frame insertion mutagenesis and site-directed mutagenesis targeting
      clusters of charged residues. We find that 31 codon insertions are infrequently
      tolerated in Mtv-7 Sag, with just 1 of 14 insertion mutants functionally
      presented on the surface of B cells. Surprisingly, similar effects were observed
      with Sag mutants with substitutions at pairs of charged residues; only 2 of 6
      mutants trafficked to the plasma membrane and stimulated T cells, 1 with a
      temperature-sensitive phenotype. The data suggest that the nonfunctional Mtv-7
      Sag mutants are stringently retained in the endoplasmic reticulum due to
      conformational defects rather than disrupted interactions with MHC class II, thus
      identifying charged amino acids critical to the structural stability of viral
      superantigens.

PMID- 9568035
TI  - The simian T-lymphotropic virus STLV-PP1664 from Pan paniscus is distinctly
      related to HTLV-2 but differs in genomic organization.
AB  - We have isolated a highly divergent simian T-lymphotropic virus, STLV-PP1664,
      from a wild-caught bonobo (Pan paniscus). Previous phylogenetic analysis
      suggested that this virus represents an additional type of STLV but this has now
      become a matter of discussion. We have now obtained and analyzed the entire
      genome of STLV-PP1664. All major genes and their corresponding viral messengers
      were identified. Sequence comparison and phylogenetic analysis indicated that
      this virus, together with the closely related panp isolate, belongs to an early
      lineage within the PTLV-2 clade, differing from HTLV-2 by about 25%. In contrast
      to the HTLV-1 and HTLV-2 LTR, only two 21-bp repeats instead of three were found
      in the STLV-PP1664 LTR. Additional messengers, resulting from alternative
      splicing, potentially encode five different accessory proteins from open reading
      frames in the pX region: prorfI, porfII, ptorfV', and two isoforms of Rex. The
      amino acid sequences of these proteins are only distinctly related to the
      accessory proteins from HTLV-2. These data suggest a different genomic
      organization of the STLV-PP1664 pX region than that of HTLV-2. We conclude that
      STLV-PP1664, although related to HTLV-2, has some distinct features in the LTR
      and the pX regions, the impact of which needs further investigation. Although
      arguments pro and contra a distinct classification are nearly equally balanced,
      we propose to classify this virus as an STLV-2, designated STLV-2PP1664.

PMID- 9568036
TI  - Mutations in the Sindbis virus capsid gene can partially suppress mutations in
      the cytoplasmic domain of the virus E2 glycoprotein spike.
AB  - Assembly and budding of alphaviruses are postulated to occur by protein-protein
      interactions between sites on the cytoplasmic domain of the transmembranal
      envelope E2 glycoprotein and on the surface of the nucleocapsid protein subunits.
      Genetic data to support this model have been obtained by isolating revertants of
      two slow-growth mutants of Sindbis virus and analyzing the sequences of the genes
      encoding their structural proteins. The slow-growth phenotypes of the mutants
      were previously shown to result from site-directed mutations of 2 amino acids in
      the sequence corresponding to the 33 amino acids at the carboxyl terminus of E2,
      which are localized to the cytoplasmic face of the plasma membrane. Putative
      revertants of these two mutants with faster growth rates were isolated by
      sequential passaging of virus grown on insect cells or chicken embryo
      fibroblasts. Sequence analysis of plaque-purified viruses that grew significantly
      better than the original mutant revealed that the original E2 mutation was
      present and that there were additional amino acid changes in the virus capsid.
      Two of the latter were introduced separately into the wild-type virus cDNA and
      into the genomes of the original mutants. The new strains of virus that contained
      both capsid and E2 mutations produced many more extracellular particles than
      those with the E2 mutations alone, indicating substantial suppression of the
      original E2 mutation. Both capsid mutations appear to be localized near a
      hydrophobic pocket of the capsid, which is postulated to be the site for docking
      of hydrophobic amino acids of the E2 cytoplasmic domain. This genetic study
      provides strong support for the current models of alphavirus assembly.

PMID- 9568037
TI  - Identification of a 24-kDa polypeptide processed from the coronavirus infectious
      bronchitis virus 1a polyprotein by the 3C-like proteinase and determination of
      its cleavage sites.
AB  - We report here the identification of a 24-kDa polypeptide in IBV-infected Vero
      cells by immunoprecipitation with a region-specific antiserum raised in rabbits
      against the IBV sequence encoded between nucleotides 10,928 and 11,493.
      Coexpression, deletion, and mutagenesis studies have demonstrated that this
      protein is encoded by ORF 1a from nucleotide 10,915 to 11,544 and is released
      from the 1a polyprotein by the 3C-like proteinase-mediated proteolysis. A
      previously predicted Q-S (Q3462S3463) dipeptide bond encoded by the IBV sequence
      from nucleotide 10,912 to 10,917 is identified as the N-terminal cleavage site,
      and a Q-N (Q3672N3673) dipeptide bond encoded by the IBV sequence between
      nucleotides 11,542 and 11,547 is identified as the C-terminal cleavage site of
      the 24-kDa polypeptide.

PMID- 9568038
TI  - Recombinant swinepox virus expressing beta-galactosidase: investigation of viral
      host range and gene expression levels in cell culture.
AB  - Swinepox virus (SPV) has been proposed as a potential vector for generating
      recombinant vaccines for swine. However, little is known about important aspects
      of SPV biology, such as the functionality of SPV promoters or the host range of
      SPV. Using a transient expression assay, well-characterized vaccinia virus
      promoters were shown to be active in cells infected with SPV. A recombinant SPV
      expressing beta-galactosidase (beta-gal) was constructed and characterized. The
      E. coli LacZ gene was placed under the control of a strong vaccinia synthetic
      early/late promoter and was inserted by homologous recombination in a noncoding
      region of the SPV genome. The recombinant SPV expressing beta-gal was used to
      characterize the host range of the virus by measuring protein expression and
      virus production in different cell lines. In general, SPV expressed more protein
      and grew more efficiently than vaccinia virus in porcine cell lines.
      Surprisingly, the recombinant SPV was able to infect and replicate in several
      cell lines of nonswine origin. The virus directed regulated early and late gene
      expression of beta-gal in those cells and formed blue plaques in cell monolayers
      in the presence of X-gal. Upon infection with the recombinant SPV, there was a
      significant level of viral replication, and the virus can be serially passaged in
      some nonswine cell lines. The data presented suggest that despite the strict host
      tropism of SPV, the virus exhibits a relatively broad host range in cell culture.

PMID- 9568039
TI  - Vaccinia virus E3L protein is an inhibitor of the interferon (i.f.n.)-induced 2
      5A synthetase enzyme.
AB  - Induction of apoptosis in mammalian cells by double-stranded (ds) RNA-dependent
      enzymes, protein kinase (PKR), and 2-5A-synthetase/RNase L (referred to as the 2
      5A system) might be a mechanism mediating anticellular and antiviral actions of
      interferon (i.f.n.). To counteract the effect of i.f.n., animal viruses have
      acquired genes that block specific i.f.n. pathways. Among poxviruses, vaccinia
      virus (VV) encodes E3L, a dsRNA-binding protein, which inhibits activation of
      i.f.n.-induced PKR. It has been proposed that E3L might also block activation of
      the 2-5A system, but direct proof is lacking. To establish if E3L inhibits the 2
      5A system, we have developed a method to assay apoptosis induced by increased
      production of enzymes in the 2-5A pathway, as well as of their putative
      modulators. This assay is based on the use of cells derived from homozygous PKR
      knockout mice (Pkr-/-) infected with a VV mutant lacking E3L (delta E3L) and
      transiently transfected with a luciferase reporter gene together with plasmid
      vectors expressing 2-5A-synthetase, RNase L, or E3L, all controlled by the same
      inducible promoter. We found that expression of 2-5A-synthetase inhibited
      luciferase activity in a dose-response manner, reaching inhibition values of 80%
      relative to transfections with control plasmids. Similar results were obtained by
      transfection with an RNase L vector, although in this case the extent of
      inhibition was further enhanced upon coexpression of 2-5A-synthetase and RNase L.
      Inhibition of protein synthesis mediated by the 2-5A system correlated well with
      induction of apoptosis. Transfection of cells with a plasmid vector expressing
      E3L together with 2-5A-synthetase completely prevented apoptosis induced by this
      enzyme. We conclude that VV E3L acts as an inhibitor of the i.f.n.-induced 2-5A
      synthetase enzyme.

PMID- 9568040
TI  - Quantitation of MoMuLV envelope protein on the cell surface.
AB  - The envelope glycoprotein (Env) of Moloney murine leukemia virus (MoMuLV) is
      proteolytically processed and transported to the cell surface where it can be
      incorporated into budding virions. Cell surface Env is frequently detected using
      an indirect immunofluorescence assay and fluorescence-activated cell sorting
      (FACS). We found that the detection of Env in this manner requires the expression
      of the MoMuLV receptor (ATRC-1) on the cell surface, and the level of envelope
      protein detected correlates with the level of receptors expressed on the cell. In
      addition, Env detection corresponds to the Env protein's ability to bind to its
      receptor and can be competed out by the addition of a truncated form of the Env
      protein. These data suggest that Env detected on the cell surface by the FACS
      assay is protein that has rebound to its receptor after being secreted or shed,
      rather than actual surface-expressed protein. In contrast, a combined
      immunoprecipitation and biotinylation assay detected equal amounts of Env on the
      surface of both receptor-lacking and receptor-expressing cell lines. The
      immunoprecipitation-biotinylation assay is therefore a more appropriate method
      for detecting surface expression of the MoMuLV envelope protein.

PMID- 9568041
TI  - Expression of human papillomavirus type 16 L1 protein in Escherichia coli:
      denaturation, renaturation, and self-assembly of virus-like particles in vitro.
AB  - Major capsid protein L1 of HPV16 was produced in a fused form in Escherichia coli
      using an inducible expression system. The protein formed insoluble aggregations
      (inclusion bodies) and the yield was more than 10% of total cell proteins. The
      inclusion bodies were isolated and solubilised with 8 M urea and the L1 proteins
      were purified by chromatographic separation. Following removal of the urea by
      gradual dialysis, the denatured L1 proteins spontaneously renatured and
      subsequently assembled into polymorphologic aggregations in vitro. Electron
      microscopy showed that the assembled material included structures resembling
      native empty capsids as well as incompletely formed capsids. After separation
      from the pool of polymorphologic structures by sucrose gradient sedimentation,
      the correctly formed virus-like particles (VLE. coliPs) were recognised by a
      HPV16 type-specific, conformational-dependent monoclonal antibody in an ELISA.
      This system offers not only a model for investigation of the intrinsic
      interactions that occur during L1 assembly, but also a potential route for
      convenient manufacture of highly purified VLP vaccines.

PMID- 9568042
TI  - The genomic sequence analysis of the left and right species-specific terminal
      region of a cowpox virus strain reveals unique sequences and a cluster of intact
      ORFs for immunomodulatory and host range proteins.
AB  - Sequencing and computer analysis of the left (52,283 bp) and right (49,649 bp)
      variable DNA regions of the cowpox virus strain GRI-90 (CPV-GRI) has revealed 51
      and 37 potential open reading frames (ORFs), respectively. Comparison of the
      structure-function organization of these DNA regions of CPV-GRI with those
      previously published for corresponding regions of genomes of vaccinia virus,
      strains Copenhagen (VAC-COP) and Western Reserve (VAC-WR); and variola major
      virus, strains India-1967 (VAR-IND), Bangladesh-1975 (VAR-BSH); and alastrim
      variola minor virus, strain Garcia-1966 (VAR-GAR), was performed. Within the left
      terminal region under study, an extended DNA sequence (14,171 bp), unique to CPV,
      has been found. Within the right region of the CPV-GRI genome two segments, which
      are unique to CPV DNA (1579 and 3585 bp) have been found. Numerous differences
      have been revealed in the genetic structure of CPV-GRI DNA regions, homologous to
      fragments of the genomes of the above-mentioned orthopoxvirus strains. A cluster
      of ORFs with structural similarity ot immunomodulatory and host range function of
      other poxviruses have also been detected. A comparison of the sequences of ORF B,
      crmA, crmB, crmC, IMP, and CHO hr genes of CPV Brighton strain (CPV-BRI) with the
      corresponding genes in strain GRI-90 have revealed an identity at the amino acid
      level ranging from 82 to 96% between the two strains. The findings are
      significant in light of the recent demonstration of CPV as an important poxvirus
      model system to probe the precise in vivo role(s) of the unique virally encoded
      immunomodulatory proteins. Also, the presence of a complete and intact repertoire
      of immunomodulatory proteins, ring canal proteins family, and host range genes
      indicates that CPV may have been the most ancient of all studied orthopoxviruses.

PMID- 9568043
TI  - The African swine fever virus proteins p54 and p30 are involved in two distinct
      steps of virus attachment and both contribute to the antibody-mediated protective
      immune response.
AB  - The nature of the initial interactions of African swine fever (ASF) virus with
      target cells is only partially known, and to date only the ASF virus protein p12
      has been identified as a viral attachment protein. More recently, antibodies to
      viral proteins p54 and p30 have been shown to neutralize the virus, inhibiting
      virus binding and internalization, respectively. Therefore, we investigated the
      role of these proteins in the receptor-mediated ASF virus endocytosis in swine
      macrophages, the natural host cells. Proteins p54 and p30, released from ASF
      virus particles after treatment of virions with a nonionic detergent, bound to
      virus-sensitive alveolar pig macrophages. Binding of these proteins was found to
      be specifically inhibited by neutralizing antibodies obtained from a convalescent
      pig or from pigs immunized with recombinant p54 or p30 proteins. The baculovirus
      expressed proteins p54 and p30 retained the same biological properties as the
      viral proteins, since they also bound specifically to these cells, and their
      binding was equally inhibited by neutralizing antibodies. Binding of 35S-labeled
      recombinant p54 and p30 proteins to macrophages was specifically competed by an
      excess of unlabeled p54 and p30, respectively. However, cross-binding inhibition
      was not observed, suggesting the existence of two different saturable binding
      sites for these proteins in the susceptible cells. In addition, protein p54
      blocked the specific binding of virus particles to the macrophage, while protein
      p30 blocked virus internalization. Both proteins independently prevented virus
      infection and in a dose-dependent manner, suggesting that binding interactions
      mediated by both proteins are necessary to give rise to a productive infection.
      The relevance of blockade of virus-cell interactions mediated by p54 and p30 in
      the protective immune response against ASF virus was then investigated.
      Immunization of pigs with either recombinant p54 or p30 proteins induced
      neutralizing antibodies which, as expected, inhibited virus attachment or
      internalization, respectively. However, immunized pigs were not protected against
      lethal infection and the disease course was not modified in these animals. In
      contrast, immunization with a combination of p54 and p30 proteins simultaneously
      stimulated both virus neutralizing mechanisms and modified drastically the
      disease course, rendering a variable degree of protection ranging from a delay in
      the onset of the disease to complete protection against virus infection. In
      conclusion, the above results strongly suggest that proteins p54 and p30 mediate
      specific interactions between ASF virus and cellular receptors and that
      simultaneous interference with these two interactions has a complementary effect
      in antibody-mediated protection.

PMID- 9568044
TI  - Isolation of a mutant of Arabidopsis thaliana carrying two simultaneous mutations
      affecting tobacco mosaic virus multiplication within a single cell.
AB  - Tobacco mosaic virus strain Cg (TMV-Cg) infects A. thaliana systemically. In
      order to identify host factors involved in the multiplication of TMV-Cg, we
      isolated mutant of A. thaliana from an M2 population mutagenized by fast neutron
      irradiation, in which the accumulation of the coat protein in upper systemic
      leaves was reduced to low levels. The phenotype of the mutant, YS241, was
      controlled primarily by a single nuclear recessive mutation named tom2-1, which
      was distinct from tom1, a separate mutation which also affects TMV-Cg
      multiplication. The tom2-1 mutation affected the accumulation of TMV-related RNAs
      in protoplasts in a tobamovirus-specific manner, suggesting that the wild-type
      TOM2 gene product is necessary for efficient amplification of TMV-related RNAs
      within a single cell, through specific interaction with virus-coded factors.
      Furthermore, we found that YS241 contained a single dominant modifier named ttm1,
      which increased the efficiency of multiplication of TMV-Cg and a tomato strain of
      TMV in a tom2-1 genetic background, both in plants and in protoplasts. We propose
      that the ttm1 element might be a translocated form of the TOM2 gene.

PMID- 9568045
TI  - DNA packaging by L1 and L2 capsid proteins of bovine papillomavirus type 1.
AB  - Encapsidation of circular DNA by papillomavirus capsid protein was investigated
      in Cos-1 cells. Plasmids carrying both an SV40 origin of replication (ori) and an
      E. coli ori were introduced into Cos-1 cells by DNA transfection PV capsid
      proteins were supplied in trans by recombinant vaccinia viruses. Pseudovirions
      were purified from infected cells and their packaged DNA was extracted and used
      to transform E. coli as an indication of packaging efficacy. VLPs assembled from
      BPV-1 L1 alone packaged little plasmid DNA, whereas VLPs assembled from BPV-1 L1
      + L2 packaged plasmid DNA at least 50 times more effectively. BPV-1 L1 + L2 VLPs
      packaged a plasmid containing BPV-1 sequence 8.2 +/- 3.1 times more effectively
      than a plasmid without BPV sequences. Using a series of plasmid constructs
      comprising a core BPV-1 sequence and spacer DNA it was demonstrated that BPV VLPs
      could accommodate a maximum of about 10.2 kb of plasmid DNA, and that longer
      closed circular DNA was truncated to produce less dense virions with shorter
      plasmid sequences. The present study suggests that packaging of genome within PV
      virions involves interaction of L2 protein with specific DNA sequences, and
      demonstrates that PV pseudovirions have the potential to be used as DNA delivery
      vectors for plasmids of up to 10.2 kb.

PMID- 9568046
TI  - Chromosomal aberrations induced by BK virus T antigen in human fibroblasts.
AB  - Human fibroblasts, transfected with a recombinant DNA containing the neo gene and
      BK virus (BKV) early region, which expresses BPV large T antigen (TAg), show
      cytogenetic alterations characterized by dicentric chromosomes and other
      structural aberrations such as deletions, duplications, translocations, and ring
      chromosomes. Such alterations were absent or significantly less frequent in human
      fibroblasts transfected with a plasmid expressing only the neo gene. The
      chromosome damage in BKV-transfected cells was evident before the appearance of
      the morphologically transformed phenotype and therefore seems to be a primary
      effect of TAg expression in human cells. The specific pattern of chromosome
      aberrations suggests the prevalence of an indirect clastogenic effect, determined
      by the inhibition of p53 regulatory functions on genome stability by BKV TAg. Due
      to the widespread distribution of BKV in the human population and to the latent
      state of BKV DNA in many human organs, the clastogenic activity of BKV TAg may
      potentially participate in an oncogenic process involving BKV latently infected
      cells.

PMID- 9568048
TI  - Cytostasis and cancer chemoprevention: investigating the action of
      triphenylselenonium chloride in in vivo models of mammary carcinogenesis.
AB  - In this study, specific aspects of the cancer chemopreventive activity of
      triphenylselenonium chloride were investigated. The research was carried out in
      three in vivo models of MNU-induced mammary carcinogenesis in rats: a) a newly
      developed model characterized by the rapid but time-dependent appearance of
      intraductal proliferations, ductal carcinoma in situ and adenocarcinomas; b) a
      conventional model which took 5 months for full expression of all palpable
      tumors; and c) a late stage model which used tumor-bearing rats as the target
      population. Our work indicated that a) triphenylselenonium was able to delay the
      progression of premalignant to malignant lesions; b) chronic exposure to
      triphenylselenonium was required to sustain its cancer inhibitory activity; and
      c) triphenylselenonium failed to induce regression of established mammary
      carcinomas or suppress the emergence of new tumors when it was given at the late
      stage of carcinogenesis. These findings highlight the importance of understanding
      the range of activity of a given chemopreventive agent in order to maximize the
      probability of a successful outcome in the design of any future intervention
      trial.

PMID- 9568047
TI  - Expression of the kidney-associated differentiation glycoprotein gp160 and
      resistance to the antitumor effects of interferon alpha in renal cell carcinomas.
AB  - BACKGROUND: Alpha interferon (IFN-alpha) is commonly used to treat patients with
      advanced renal cell carcinoma (RCC). We previously reported that resistance of
      RCCs to IFN-alpha in vitro correlated with the expression of a cell-surface
      glycoprotein of 160,00 kD molecular weight (gp160) which we subsequently
      identified as aminopeptidase A. MATERIALS AND METHODS: To directly test the role
      of gp160/APA in IFN-resistance, we stably introduced the gp160/APA cDNA into IFN
      sensitive SK-RC-49 cells resulting in the expression of an enzymatically active
      gp160/APA protein. In addition, to determine if gp160/APA expression could
      function as a marker of IFN-resistance in vivo, we assessed gp160/APA protein
      levels in autologous normal kidney and primary renal cancer specimens from 29
      patients half of which were randomized to receive adjuvant IFN-alpha therapy
      following nephrectomy. RESULTS: Four clones which possessed varying amounts of
      gp160/APA specific enzyme activity were assayed for sensitivity to the
      antiproliferative effects of IFN-alpha. All four clones exhibited sensitivity to
      IFN-alpha similar to that observed with parental SK-RC-49 cells. The analysis of
      tumor tissue detected no significant difference between the mean level of
      gp160/APA in tissue from control and IFN-alpha treated patients (1.33 A.U. versus
      0.9981 A.U., p = 0.23); however, the mean gp160/APA level was significantly less
      in tumor tissue (mean = 1.15 A.U.) compared to normal tissue (mean = 2.15 A.U.; p
      < 0.00001). Within the IFN-alpha treated group, tumor gp160/APA levels did not
      correlate with the development of metastases or survival (p = 0.469).
      CONCLUSIONS: These data indicate that gp160/APA does not directly convey IFN
      resistance to RCC cells and suggest that expression of gp160/APA in primary RCCs
      does not predict the benefit of IFN-alpha therapy.

PMID- 9568049
TI  - Liver metastasis of a human colorectal cancer containing two actively growing
      subclones.
AB  - A common pattern of karyotype evolution between clones involves gradual changes
      of one or only a few chromosomes. Karyotypes of one day-old cultures derived from
      a tumor nodule of colorectal cancer liver metastasis were studied by GTG
      chromosome banding. Two karyotypically distinct aneuploid CC-9-a and CC-9-b
      clones were found respectively, at about 1:3 ratio. Both clones showed common
      karyotype characteristics with the same number of copies for 13 normal and four
      marker chromosomes, indicating their common genetic origin. However, CC-9-b
      differed from CC-9-a by the loss of one copy each of eight normal and four common
      marker chromosomes. This mode of gross single-chromosome losses is also seen in
      established cell lines, and probably plays an important role in the drastic
      chromosome changes associated with the duplication-reduction cycle of karyotype
      evolution.

PMID- 9568051
TI  - Doxorubicin and vincristine with methionine depletion contributed to survival in
      the Yoshida sarcoma bearing rats.
AB  - Several anti-cancer agents show increased toxicity if administered with
      methionine-depleting total parenteral nutrition (Met-deplete TPN). Changes in the
      cell cycle due to Met-deplete TPN were investigated, and then the enhancement of
      the anti-tumor effects of serial combinations of doxorubicin (ADM), a drug acting
      on late S-G2 phase and vincristine (VCR), an antimitotic drug, under Met-deplete
      TPN was also examined in the tumor-bearing rats. According to the fraction of
      labeled mitosis, within 3 to 4 days after the introduction of Met-deplete TPN in
      the ascites type Yoshida sarcoma (YS) -bearing rats, the cell cycle of the tumor
      cells showed marked delay and the fraction of labeled mitosis decreased to less
      than 70%. However, this delay was recovered immediately after methionine
      infusion, with on increase in the labeled mitotic cell population. In the
      experiment using solid type YS-bearing rats, ADM was administered
      intraperitoneally under Met-deplete TPN for 8 days, followed by intraperitoneal
      VCR administration with methionine-containing TPN for 3 days, and then fed on
      solid food and water ad libitum until death. This serial combination of Met
      deplete TPN with ADM and VCR resulted in marked suppression of the tumor and
      prolonged survival in comparison to the control groups with a significant
      difference (p < 0.001) (generalized Wilcoxon test).

PMID- 9568050
TI  - Tumor growth suppression by a mouse/human chimeric anti-CEA antibody and
      lymphokine-activated killer cells in vitro and in SCID mouse xenograft model.
AB  - The mouse/human chimeric antibody Ch F11-39, recently generated by ourselves,
      shows the same high specificity and affinity for carcinoembryonic antigen (CEA)
      as those of its parental mouse monoclonal antibody. Ch F11-39 is capable of
      mediating antibody-dependent cell-mediated cytotoxicity (ADCC) with human
      peripheral blood lymphocytes (PBL). Interleukin-2 (IL-2) modulates the function
      of immunocytes, in particular inducing lymphokine-activated killer (LAK) cells
      and enhancing ADCC. In the present study, we therefore tested the combination
      immunotherapy of Ch F11-39 with LAK cells in vitro and in severe combined
      immunodeficiency (SCID) mice bearing human CEA-producing tumors. In vitro
      experiments using human gastric tumor cell lines, Ch F11-39 effectively mediated
      ADCC against CEA-positive MKN-45 cells, but not against CEA-negative cells. The
      specificity of ADCC for Ch F11-39 was demonstrated by experiments with irrelevant
      target cells or irrelevant antibody. ADCC activity of PBL with Ch F11-39 was
      enhanced by double after preincubation with IL-2 at 10 U/ml. The concentration of
      Ch F11-39 required for 50% maximal cell killing was about 0.25 microgram/ml at 10
      U/ml of IL-2. Increasing ADCC was triggered by IL-2 earlier (1 day) than the
      generation of LAK cells (3 days). Control human IgG blocked the ADCC, suggesting
      that the enhancement of ADCC by IL-2 may be caused by activation of effector
      cells expressing Fc receptors. In vivo anti-tumor activity of combined
      immunotherapy was estimated using SCID mice inoculated s.c. with 1 x 10(7) MKN-45
      cells. The i.v. administration of LAK cells and i.p. administration of Ch F11-39
      and IL-2 produced a marked growth inhibition of MKN-45 tumors in SCID mice (about
      50% reduction in tumor size as compared to the control untreated group, measured
      15 days after treatment). In summary, the enhanced antitumor activity of Ch F11
      39 with LAK cells suggests that it might be a useful immunotherapeutic reagent
      for CEA-expressing tumors.

PMID- 9568052
TI  - beta 1-Integrin expression in papillary thyroid carcinoma.
AB  - beta 1-integrins are widespread adhesion molecules which belong to a family of
      heterodimeric membrane glycoproteins and consist of two subunits, alpha and beta.
      Integrins seem to play an important role in the spreading and metastasis of
      malignant tumors. We investigated the expression and distribution of these
      adhesion molecules on papillary thyroid carcinomas by immunohistochemistry on
      formalin-fixed, paraffin embedded cancer tissues. We estimated the beta 1
      integrin expression in cancerous areas in comparison to normal adjacent thyroid
      tissue. Our results revealed a highly significant difference in all investigated
      parameters between cancer and normal thyroid cells (p < 0.0001). Comparing our
      findings with the metastatic potential of the primary thyroid tumors, our results
      show that beta 1-integrin expression could be used as a prognostic parameter for
      papillary thyroid tumors.

PMID- 9568053
TI  - Long-term primary human tumor cell cultures and mixed autologous tumor-lymphocyte
      cultures for adoptive specific antitumoral immunotherapy.
AB  - Anticancer immunotherapy may improve the body's cancer defences, quality of life
      and survival. Encouraging treatment models have been proposed, namely the non
      specific LAK and ALT cell therapies; the relatively specific TIL/CTL cell therapy
      as well as allogenic cancer vaccines; autologous cancer vaccines. A procedure to
      prepare an autologous antitumor serum for cancer therapy using ex vivo activated
      autologous cells is here reported. Peripheral blood lymphocytes obtained by
      leukaphoresis were cultured with autologous tumor cells in RPM1 1640 and rh-IL-2
      for 48 hours at 37 degrees C in a humidified, CO2 enriched atmosphere. The
      cytokine rich supernatant, as well as the activated cells in medium were frozen,
      lysed and aliquotted, frozen, and stored at -20 degrees C. The material was used
      for specific anticancer immunotherapy. Fibroblast-free tumor cells are being
      maintained in long term culture for future ex vivo sensitization of autologous
      cells.

PMID- 9568054
TI  - TGF-beta isoforms and fibroblast growth factor exhibit analogous indirect
      antioncogenic activity through triggering of intercellular induction of
      apoptosis.
AB  - TGF-beta-1 has recently been shown to trigger nontransformed effector cells to
      induce apoptosis specifically in transformed cells. This intercellular induction
      of apoptosis has been discussed as a potential control step in oncogenesis. Here
      we show that triggering of intercellular induction of apoptosis is not a non
      specific growth factor effect, but is restricted to the TGF-beta and FGF family
      of growth factors. Within the TGF-beta family, all isoforms triggered the
      intercellular induction of apoptosis with the same efficiency. This finding
      illustrates that these effects observed have been conserved throughout evolution,
      which thus points to their potential biological significance. The parallel action
      of TGF-beta and FGF in the intercellular induction of apoptosis correlates with
      the role of both families of factors in the establishment and maintenance of the
      transformed state. Autocrine loops of either growth factor seem to be recognized
      by the surrounding nontransformed cells and to evoke an apoptosis- inducing
      effect which thus prevents the survival and outgrowth of potential tumor cells.

PMID- 9568055
TI  - Growth and clonogenic assays compared for irradiated MCF-7 and Colo-205 cell
      lines.
AB  - Clonogenic assays have been the golden standard for the assessment of cytotoxic
      injury from irradiation or drugs. Since such assays are time consuming, growth
      assays, often with automatic quantifying equipment, are frequently used. Since
      these procedures do not immediately reflect loss of clonogenic capacity, it was
      considered important to validate the two procedures using gamma-irradiation (0, 2
      and 4 Gy) of two human cell lines (MCF-7 and Colo-205). The cells were growing
      exponentially in 96-well plates and crystal violet staining resulted in optical
      densities proportional to cell number. The homogeneity of optical densities
      within the plates was optimal if the wells to be measured were surrounded by
      liquid-containing ones. The slopes of the exponential growth curves were
      decreased upon irradiation. An "apparent cell survival", the mean of the three
      lowest ratios between irradiated and control cells, was defined. It was compared
      with the SF2 and SF4 as found in parallel Courtenay-Mills assays. In this work we
      found a modest underestimation of cell survival using the growth assay, ranging
      from 0 to 17 per cent in absolute terms.

PMID- 9568056
TI  - Biological activity of 6,12-dihydro-1-benzopyrano[3,4-b][1,4]benzothiazin-6-ones.
AB  - Ten 6,12-dihydro-1-benzopyrano[3,4-b][1,4]benzothiazin-6-ones (Coumarins)[1-7]
      and related coumarins [8-10] were compared for their cytotoxic activity and
      radical intensity. Among these compounds, compound 7 showed highest cytotoxic
      activity against human promyelocytic leukemic HL-60 cells. Compound 7 produced
      radicals under alkaline conditions, and showed the lowest pi-spin density at S
      atom of the molecule, suggesting the delocalization of pi-spin density. These
      data suggest the possible relation between radical intensity and biological
      activity.

PMID- 9568057
TI  - Immunohistochemical analysis of p53 expression in primary breast carcinomas.
AB  - Expression of p53 protein was investigated by immunohistochemical techniques in
      archival cases of 134 primary breast carcinomas comprising 13 comedo ductal
      carcinoma in situ (DCIS), 105 invasive ductal carcinomas, 7 contained the comedo
      DCIS component adjacent to the invasive ductal component, 5 invasive lobular
      carcinomas, three colloid carcinomas and one medullary carcinoma. Overexpression
      of p53 gene product was studied to determine the association with clinico
      pathological parameters and also its relationship to c-erbB2. Overexpression of
      p53 protein was observed in 31% (4/13) of comedo DCIS, 37% (39/105) of invasive
      ductal carcinomas, 57% (4/7) of carcinomas containing both the in situ and
      invasive lesions and all medullary carcinomas. A significant relationship (p <
      0.05) was observed between strong immunoreactivity of p53 protein and absence of
      estrogen receptor, histological grade and c-erbB2 but not with lymph node
      metastases or age of patient. These observations suggest that overexpression of
      p53 protein may play an important role in tumor progression from noninvasive to
      invasive in some breast carcinomas and may have potential as an indicator for
      poorer prognosis.

PMID- 9568058
TI  - Focal expression of thymidine phosphorylase associates with CD31 positive
      lymphocytic aggregation and local neo-angiogenesis in non-small cell lung cancer.
AB  - Platelet-derived endothelial cell growth factor (PDECGF) also called thymidine
      phosphorylaze (TP) has been shown to have considerable angiogenic activity. 141
      cases of early stage non-small cell lung cancer were stained for TP and vascular
      grade using the P-GF.44C and JC70 MoAbs, respectively. The early steps of TP
      activation could be identified in 27 cases, where one or two foci of cancer cell
      TP overexpression occurred within a general pattern of negative/weak staining.
      Thirty-three foci of overexpression were analyzed for the local microvessel
      density in the adjacent stroma, assessed by microvessel counting (MC) and
      Chalkley Score (CS) comparatively with the remaining TP negative tumor areas. The
      degree of local inflammatory (lymphocyte and macrophage) infiltration was also
      assessed. A statistically significant increase of mean MC and mean CS was
      observed in areas of TP overexpression in both low and high angiogenesis cases.
      Overall, the mean MC in overexpressing areas, assessed in 250x fields, was 20.4
      +/- 12.8 vs. 13.6 +/- 9.5 in areas with no TP expression (p = 0.0001). The mean
      CS was 5.7 +/- 3.3 and 4.0 +/- 2.1, respectively (p = 0.0003). Ten out of 19
      (54%) cases with low lymphocytic infiltration showed marked stromal lymphocytic
      infiltration in the area of focal TP overexpression (p = 0.01). The present study
      provides further evidence of a direct association of TP and the process of
      angiogenesis in non-small cell lung cancer.

PMID- 9568059
TI  - Expression of interleukin-8 receptors on tumor cells and vascular endothelial
      cells in human breast cancer tissue.
AB  - Recently, we demonstrated the presence of Interleukin-8 (IL-8) in human breast
      cancer (HBC) tissue. We hypothesize that the IL-8 receptors are present and play
      a role in tumor cell and vascular endothelial cell (VEC) activation (e.g.
      proliferation and angiogenesis). MATERIALS AND METHODS: Immunohistochemical
      analysis for IL-8 receptors (IL-8RA and IL-8RB) was performed on 43 malignant and
      8 benign breast tissue samples. RESULTS: Tumor cells expressed IL-8RA and IL-8RB
      in all of the malignant specimens. Only 50% of the benign ductal epithelial cell
      (DEC) samples expressed these receptors. The majority of small vessel endothelial
      cells (SVEC) expressed IL-8RA and IL-8RB, while large vessel endothelial cells
      (LVEC) showed primarily IL-8RB expression. CONCLUSIONS: Our results demonstrate
      that tumor and VEC express the IL-8 receptors and likely play a role in
      regulating tumor and VEC activation which controls proliferation, angiogenesis
      and metastasis in HBC.

PMID- 9568060
TI  - Tissue distribution and metabolism of radioiodinated DTPA0, D-Tyr1 and Tyr3
      derivatives of octreotide in rats.
AB  - Lesions containing somatostatin receptors (SSR) in rats and in man can be
      visualized in vivo using radiolabeled octreotide (OCT) analogs. SSR scintigraphy
      was initially performed with [123I-Tyr3]OCT and later with [111In-DTRA0]OCT. With
      the latter the residence time of radioactivity (111In) in SSR-positive targets is
      prolonged, most probably due to the DTPA group. Therefore, we hypothesized that
      its presence might also affect the metabolism of radioiodinated DTPA-OCT analogs.
      [D-Tyr1]OCT, [DTPA0, D-Tyr1]OCT, [Tyr3]OCT and [DTPA0,Tyr3]OCT were synthesized,
      and all 4 showed high and specific binding to the SSR in vitro, with IC50 values
      in the nanomolar range. The rate of internalization of the 4 radioiodinated OCT
      analogs by mouse AtT20 pituitary tumors cells was in accordance with the IC50
      values. The metabolism and tissue distribution of the 4 radioiodinated analogs
      were investigated in rats at 4, 24 and 48 hours pi, and the tissue vs blood
      ratios were calculated. High uptake of all OCT analogs was found in the
      somatostatin receptor-positive tissues at 4 hours, but only remained high at 24
      and 48 hours with [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT. Kidney uptake of
      [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT was also high. Blood clearance and
      disappearance from muscle was rapid for all 4 analogs. Urinary excretion of [125I
      D-Tyr1]OCT, [DTPA0,125I-D-Tyr1]OCT,[125I-Tyr3]OCT and [DTPA0, 125I-Tyr3]OCT
      amounted to 63%, 67%, 31% and 80% of injected dose respectively. [DTPA0,125I-D
      Tyr1]OCT showed highest tissue to blood ratio and residence time in SSR-positive
      tissues, such as adrenals (ratio: 31, 79, and 66 at 4, 24 and 48 hours
      respectively) and pancreas (ratio: 14, 48 and 44 at 4, 24 and 48 hours
      respectively). CONCLUSION: The position of the Tyr residues and the addition of
      the DTPA group greatly influence the biodistribution of radioiodinated [Tyr]OCT
      analogs.

PMID- 9568061
TI  - Effects of c-myc oncogene modulation on differentiation of human small cell lung
      carcinoma cell lines.
AB  - Amplification and over-expression of oncogenes of the myc family are related to
      the prognosis of certain solid tumors such as small cell lung cancer (SCLC). For
      SCLC, c-myc is the oncogene most consistently found to correlate with the end
      stage behaviour of the tumour, in particular with survival after chemotherapeutic
      treatment. C-myc is important in many cellular processes such as proliferation,
      differentiation and apoptosis. In the present study the relationship between c
      myc and differentiation was analyzed by down-regulation of endogenous c-myc
      protein, using two approaches: first by coculturing with antisense (AS)
      oligodeoxynucleotides (ODN) in the human SCLC cell line GLC4 and its 6-fold
      cisplatin resistant subline GLC4-CDDP, second by stable transfection of GLC4-CDDP
      with a dexamethasone-inducible AS c-myc expression vector. Basic characterization
      of the differentiation status of GLC4 and GLC4-CDDP showed a decrease in
      neuroendocrine differentiation in GLC4-CDDP compared to GLC4 Cytokeratin was
      absent in both cell lines. No significant differences in expression of adhesion
      molecules or myeloid antigens were observed between the lines. Vimentin
      expression was higher in GLC4-CDDP compared to GLC4 (AS c-myc ODN)-induced growth
      inhibition and down-regulation of endogenous c-myc protein further decreased
      neuroendocrine differentiation (CD57 positive cells) in GLC4-CDDP without
      affecting the expression of other antigens such as vimentin (intermediate
      filament),CD15 (myeloid antigen) and VLA-alpha 4 (adhesion molecule) and did not
      alter the expression of these antigens in GLC4 (AS c-myc RNA)-induced growth
      inhibition did not significantly affect the expression of the tested antigens in
      the AS c-myc transfected GLC4-CDDP/AS cell line. No effect of nonsense c-myc ODN
      or dexamethasone-induced control RNA (controls) was observed.

PMID- 9568062
TI  - Antitumor activity of novel octalactin A analogs in murine leukemia cells in
      vitro.
AB  - Octalactin A and B (code names K1 and K2) are eight-membered-ring lactones from a
      marine bacterium. K1 is reportedly cytotoxic. Since access to this natural
      product is severely limited, the entire synthesis of K1 has been achieved in K.
      Buszek's laboratory, and several of its structural and stereochemical analogs
      (code names K3-K9) have been tested for their ability to prevent murine L1210
      leukemic cells from synthesizing macromolecules and growing in vitro. At 50
      microM, K1 is inactive and the eight-membered lactone K4, an oxocene, is the only
      compound found to inhibit tumor cell growth by about 90% in the L1210 system. The
      long-term inhibition of L1210 cell growth by K4 is concentration dependent (IC50
      around 10 microM) and not reversible following drug removal. The delayed and
      weaker cytotoxic effects of K4 suggest that the inhibition of tumor cell
      proliferation observed 1-4 days after K4 treatment is not solely caused by drug
      cytotoxicity. When compared to a spectrum of representative anticancer drugs,
      higher concentrations of K4 must be used to maximally inhibit tumor cell growth.
      In contrast to its antiproliferative activity, 50 microM K4 fails to alter the
      rates of DNA, RNA and protein synthesis in L1210 cells. This discrepancy between
      the ability of K4 to inhibit macromolecule synthesis and leukemic cell growth
      suggests that other molecular targets are involved in the antitumor action of
      this drug. At 50 microM, K4 inhibits the polymerization of purified tubulin by
      about 45%, and therefore may be a novel microtubule de-stabilizing drug weaker
      than vincristine. Even though other mechanisms may be involved in its antitumor
      action, the ability of K4 to partially disrupt microtubule dynamics indirectly
      suggests that this synthetic oxocene may be a cell cycle-specific anticancer drug
      that blocks mammalian cells in M-phase.

PMID- 9568063
TI  - Glutathione and glutathione S-transferases in human squamous cell carcinomas of
      the larynx and GSTM1 dependent risk.
AB  - BACKGROUND: The aim of the present study was to establish the risk of squamous
      cell carcinoma (SCC) of the larynx associated with the congenital absence of
      glutathione S-transferase M1 (GSTM1), and to describe the expression of the
      isoenzymes GSTA1/2, GSTP1-1, and GSTM1 and glutathione (GSH) content in healthy
      and tumoral larynx tissue. MATERIAL AND METHODS: Blood samples from 160 SCC male
      patients and 158 controls were phenotyped for GSTM1 by ELISA. Using 37 paired
      samples (normal and tumour specimens) from cancer patients we carried out a
      descriptive study of enzyme activity by ELISA (GSTs) and Ellman's as say (GSH)
      RESULTS: GSTM1 null phenotype was more common in the SCC group than in controls
      (OR 1.9, CIs 1.18-3.05, p = 0.004). Total GST activity was higher in tumour
      samples than in matched healthy tissue (2.2-fold, p-0.00001), being largely
      determined by GSTP1-1 (1.9-fold increased in malignant tissue; p = 0.0003). The
      GSH content was also significantly higher in SCC than in normal mucosa (1.9-fold,
      p = 0.0007). CONCLUSIONS: We confirmed the GSTM1-dependent risk for larynx cancer
      among smokers. The overexpression of the GST/GSH system in tumours reported here
      indicates their possible role in chemoresistance to pharmacological therapy.

PMID- 9568064
TI  - Phorbol ester induces differentiation of a human prostatic cancer cell line TSU
      Pr1 into cells with characteristics of microglia.
AB  - The effects of various reagents on the induction of differentiation of the human
      prostatic cancer cell line, TSU-Pr1, were examined. Among these agents, the
      phorbol ester, TPA, almost completely suppressed cell proliferation at the
      concentration of 10(-8) M, and induced remarkable morphologic changes yielding
      cells with the microglial feature of an ameboid and/or ramified shape. More than
      90% of the cells underwent the induction of morphologic changes by day 7 after
      treatment with 10(-8) M TPA. The expression of reliable microglial markers, alpha
      naphthyl acetate esterase activity and CD11b, was observed in the differentiated
      cells. The data presented here suggest that TPA induces differentiation of a
      human prostate cancer cell line into cells with the characteristics of microglia.

PMID- 9568065
TI  - Momordins inhibit both AP-1 function and cell proliferation.
AB  - The activation of Jun/Fos is a crucial factor in transmitting the tumor promoting
      signal from the extracellular environment to nuclear transcription machinery. One
      of the final steps in signal transduction is the binding of Jun/Fos to the AP-1
      site in order to express gene transcription. Utilizing this concept, we screened
      about 100 extracts of natural plants to search for a Jun-Fos function inhibitor.
      The methanol extract of Ampelopsis radix reduced Jun/Foc retardation remarkably.
      The active principles of the extract were isolated and purified by repeated
      column chromatography and their structures were identified as oleanolic acid
      glycosides known as momordin I, Id, and Ie. These compounds reduced the Jun/Fos
      DNA interaction and their activities were quantitated with liquid scintillation
      counting of corresponding bands. Among them, momordin I had the strongest
      inhibitory activity, with an IC50 value of 22.8 micrograms/ml. The methanol
      extract and momordin I, Id and Ie also showed cell cytotoxicity against human
      cancer cell lines. As expected from a gel shift assay, momordin I showed the
      strongest cytotoxicity and its IC50 value was from 7.280 micrograms/ml to 16.05
      micrograms/ml depending on the cell line. With these data, it may be concluded
      that the mechanism of anticancer activity of momordin I comes from its inhibitory
      effect on the protein-DNA interaction. The in vivo test was done only with the
      methanol extract. The extract showed measurable anticancer activity against
      murine colon cancer. The wet tumor weight reduction rate was 17.73% at 90 mg/kg
      dose. We suggest that the Jun/Fos-DNA interaction results in cell cytotoxicity.

PMID- 9568066
TI  - Histoculture drug response assay, a possible examination system for predicting
      the antitumor effect of aromatase inhibitors in patients with breast cancer.
AB  - Histoculture drug response assay (HDRA) systems have been used in evaluating the
      cytotoxic effects of chemotherapeutic agents for many kinds of advanced cancers.
      We have adapted the HDRA system to estimate the antitumor effect of aromatase
      (estrogen synthetase) inhibitors on breast cancer. Small pieces of breast cancer
      tissue specimens were placed onto a collagen-matrix filled with medium containing
      testosterone (a substrate for aromatase) or testosterone plus an aromatase
      inhibitor. At the end of culture, [3H]-thymidine incorporation was measured in
      aliquots of the histocultured specimens after 10 days culture. The increment of
      thymidine incorporation in testosterone-treated specimens to that of control
      provides an index of existence of aromatase and estrogen-dependency, since
      converted estradiol from added testosterone by aromatase stimulates the
      incorporation. The decrease in the index of "testosterone + aromatase
      inhibitor"/"testosterone" indicates the antitumor effect of the aromatase
      inhibitor on breast cancer. Twenty-one 25 breast cancer surgical specimens were
      successfully cultured, and 6 showed the increased incorporation of [3H]-thymidine
      by testosterone. Aromatase inhibitor blocked this stimulation in these 6
      specimens. These results suggested that this antitumor effect is related to the
      inhibition of aromatase and the aromatase inhibitor would be effective for
      individual patients with breast cancer which responds to testosterone in this
      histoculture assay system. The histoculture technique we used here is therefore
      expected to be useful in predicting the efficacy of aromatase inhibitors for
      individual patients with breast cancer.

PMID- 9568067
TI  - A new calyculin derivative from the sponge Theonella swinhoei is a novel and
      potent inhibitor of tumor cell proliferation.
AB  - A novel calyculin derivative was isolated from the marine sponge Theonella
      swinhoei. Using human and animal tumor cell lines and freshly explanted
      peripheral blood cells, we investigated several biological effects of this
      natural product (i.e. cell growth, cytotoxicity, induction of differentiation and
      apoptosis). The new calyculin exhibited a dose-dependent cytotoxicity against
      various cell lines from different species and tissues. The ID50 values ranged
      between 20 and 90 ng/ml. Viability of a multidrug resistant HELA subclone was not
      affected. Apoptosis of the Hodgkin's lymphoma cell line HDLM-2 induced by
      antiserum was not prevented by the substance. A reduced drug sensitivity of the
      monocytic cell line MONOMAC-6 could be observed after induction of
      differentiation of these cells by phorbol ester and lipopolysaccharide. Even so,
      non-dividing peripheral blood cells were also resistant to the action of the
      calyculin derivative, suggesting that the cytotoxin may act preferentially on
      proliferating cells rather than on quiescent cells. Our data introduce a new
      calyculin as a marine natural product with interesting features stimulating
      further studies as a chemotherapeutic or investigational drug.

PMID- 9568068
TI  - Effect of FR143430, a novel cytokine suppressive agent, on adenocarcinoma colon26
      induced cachexia in mice.
AB  - Cancer cachexia, characterized by weight loss and progressive tissue wasting, has
      been postulated to be mediated by cytokines. In this study the effect of
      FR143430, (2-(4-fluorophenyl)-4, 5, 6, 7-tetrahydro-3-(4-pyridyl)pyrazolo[1, 5
      a]pyrimidine monohydrochloride), an inhibitor of Interleukin-1 and Tumor necrosis
      factor-a (TNF- a), on adenocarcinoma colon26-induced cachexia was investigated in
      mice. Tumor growth was not affected. Nevertheless, treatment with FR143430 (0.1
      to lmg) into the tumor resulted in the attenuation of the reduction in body
      weight, food intake, epididymal fat and carcass weight, the decrease in the
      circulating levels of triglyceride and glucose, and the increase in the
      circulating levels of total cholesterol, non esterified free fatty acid (NEFA)
      and total protein, which were induced by the presence of the tumor. However, oral
      treatment with FR143430 failed to show an inhibitory effect on cachexia
      induction. Overall, this study demonstrated that the cachexia induced by colon26
      was alleviated by the injection of FR143430 into the tumor in sufficient
      quantity, without any effect on tumor growth, suggesting the potential utility of
      cytokine suppressive agents e for the treatment of cancer cachexia.

PMID- 9568070
TI  - Effects of Sasa Health, extract of bamboo grass leaves, on spontaneous mammary
      tumourigenesis in SHN mice.
AB  - Chronic treatment with Sasa Health, extract of bamboo grass leaves obtained by
      alkaline hydrolysis, in drinking water at the concentration of 0.044%-0.088% Fe
      Chlorophyllin Na resulted in the significant inhibition of both development and
      growth of spontaneous mammary tumours in a high mammary tumour strain of SHN
      virgin mice. Limited treatment for 12 days in mice with palpable sizes of mammary
      tumours also markedly retarded the growth of the tumours. The end-bud formation
      and thymidylate synthetase activity of normal mammary glands were stimulated, but
      the formation of preneoplastic mammary hyperplastic alveolar nodules was
      inhibited by the treatment. Chronic ingestion of Sasa Health stimulated the
      excretion of urine components and decreased and increased the prolactin level and
      superoxide dismutase activity in serum, respectively. It showed no deleterious
      effects on food and water intake, body growth and any external appearance and all
      findings indicate that Sasa Health could be a promising agent for the protection
      and therapy of breast and other types of tumours.

PMID- 9568069
TI  - Myocardial infarction induces expression of midkine, a heparin-binding growth
      factor with reparative activity.
AB  - We examined midkine (MK) expression in the rat heart upon experimental myocardial
      infarction. Immunohistochemical staining revealed, 6 hours after ligation of the
      left anterior descending coronary artery, strong MK immunoreactivity in myocytes
      and endothelial cells of a non-infarcted cardiac region. The myocytes of the
      infarcted cardiac region destined for death showed only a little
      immunoreactivity. Northern blot analysis suggested that the increased
      immunoreactivity was due to increased MK synthesis. The induced MK expression is
      likely to mimic the expression during embryogenesis: MK was strong lye-expressed
      in the myocytes of embryonic heart, and the expression decreased during
      embryogenesis.

PMID- 9568071
TI  - The efficacy of immunochemotherapy with strontium (Sr) in the 1,2
      dimethylhydrazine (DMH) induced rat carcinogenetic model: ultrastructural
      characteristics of the mitochondria in the liver.
AB  - It is said that stable strontium (Sr), which exists naturally in living cells as
      a microelement, has cytoprotective effects on liver cells in mammals. We
      attempted to examine the cytoprotective and anticancer effects of Sr using the
      rat carcinogenetic model induced by DMH (1,2-dimethylhydrazine). In a comparison
      of animals given UFT, PSK and Sr or UFT and PSK, carcinogenes in the colon and
      also increases in immunosuppressive acidic protein (IAP) levels were suppressed.
      Electron microscopic observation in the Sr group revealed a tendency toward
      stabilization of the mitochondrial membrane and highly developed rough
      endoplasmic reticulum in both the right and left lobe. This tendency became more
      obvious as the duration of oral intake of Sr was prolonged. Our study suggest
      that the cytoprotective effect of Sr on mitochondria in the liver may suppress
      carcinogenesis.

PMID- 9568072
TI  - Impaired in vivo tumor growth of human pancreatic carcinoma cells retrovirally
      transduced with GM-CSF gene.
AB  - We have examined the antitumor effect of human pancreatic carcinoma cells (AsPC
      1) retrovirally transduced with mouse granulocyte macrophage-colony stimulating
      factor (GM-CSF) gene in nude mice. Growth retardation of the subcutaneous tumors
      of GM-CSF-producing AsPC-1 cells was observed, although their in vitro
      proliferation was not different from that of wild-type cells. Histological
      examination revealed infiltration of monocytic cells into the tumor of GM-CSF
      producing cells, and they were shown to be mainly CD11b positive cells by
      immunohistochemical staining. The survival of the mice inoculated
      intraperitoneally with GM-CSF- producing AsPC-1 cells was significantly prolonged
      compared with that of the mice inoculated with wild-type AsPC-1 cells. Thus, the
      expression of GM-CSF gene in human pancreatic cells induced an antitumor effect
      in vivo even in the mature T cell-deficient condition.

PMID- 9568073
TI  - Antitumor effects of SEF19, a new nonsteroidal aromatase inhibitor, on 7,12
      dimethylbenz[a]anthracene-induced mammary tumors in rats.
AB  - The antitumor and endocrine effects of a new nonsteroidal aromatase inhibitor, 2
      (imidazol-1-yl)-4,6-dimorphorino-l, 3, 5-triazine (SEF19) were examined in female
      Sprague-Dawley rats bearing estrogen dependent 7,12
      dimethylbenz[a]anthracene(DMBA)-induced mammary tumors, and the effects were
      compared with those of CGS20267. The rats bearing DMBA-induced mammary tumors
      within 6-15 weeks after the DMBA administration were divided into the treatment
      groups once a week every week, and they were treated with SEF19, CGS20267 and
      vehicle for 4 weeks. One hundred rats were sacrificed 4 hours after the last
      administration, and the remaining 60 rats were sacrificed after a 4-week recovery
      period. During the treatment and recovery period, the tumor size was generally
      smaller in the SEF19 and CGS20267-treated subgroups than in the control subgroup.
      Tumor sizes in the subgroups treated with high doses of SEF19 (25 mg/kg/day and
      50 mg/kg/2 days) were reduced to the size of the CGS20267-treated subgroup. The
      CGS20267-treated rats showed decrease in the serum estradiol level and an
      increase in the serum testosterone level. Their uterine weights were reduced.
      SEF19 treatment failed to show any effect on the serum levels of estrone,
      estradiol, testosterone and androstenedione, but it suppressed uterine weight in
      a dose-dependent manner. After the recovery period, no effect was detected in the
      serum concentrations of steroid hormones and the weight of the organs. At every
      dose used in the present study the aromatase inhibitory activity of SEF19 was
      weaker than that of CGS20267, but the inhibitory effect on mammary tumor growth
      of SEF19 at high doses was comparable to that of CGS20267. We conclude that the
      antitumor effect of SEF19 is not due to aromatase inhibition but mainly to its
      direct cytotoxicity.

PMID- 9568074
TI  - Effect of liposome-encapsulated alpha- or beta-interferon on breast cancer cell
      lines.
AB  - Experimental evidence and clinical studies have indicated that interferons (IFN)
      inhibit proliferation in a wide panel of neoplasms, including breast cancer.
      However, the antitumor activity of IFN requires the continuous presence of high
      concentrations of the drug and is associated with side effects. To explore the
      potential of liposomes as an IFN delivery system, we compared the effect of free
      or liposome-encapsulated alpha-IFN and beta-IFN on the growth of two breast
      cancer cell lines (MCF7 and MDA-MB231). Cells were cultured in the presence of
      IFN at different concentrations (500, 1000, 2000 IU/ml) or in the presence of
      multilamellar liposomes (phosphatidylcholine-phosphatidylserine at a molar ratio
      of 7:3) containing saline buffer, alpha-IFN or beta-IFN. Additional control
      groups consisted of cells cultured with alpha-IFN or beta-IFN plus empty
      liposomes. Empty liposomes were not cytotoxic and did not interfere with IFN
      activity. In both cell lines liposomes encapsulating alpha-IFN (at the highest
      lipid:drug ratio) inhibited cell growth in a manner similar to that of free alpha
      IFN, whereas liposomes encapsulating beta-IFN showed slightly, lower inhibition
      than free beta-IFN, this was more evident in MCF7 cells. The present results
      indicate that liposomes encapsulating alpha-IFN or beta-IFN were effective on the
      growth of both breast cancer cell lines, which are characterized by a different
      estrogen responsiveness, and that they might be a useful carrier system for the
      delivery of high doses of IFN.

PMID- 9568075
TI  - The p53 gene in soft tissue sarcomas: prognostic value of DNA sequencing versus
      immunohistochemistry.
AB  - BACKGROUND: The aim of this study was to compare sequencing and
      immunohistochemistry (IHC) for their ability to detect p53 mutations and to
      assess their prognostic value in soft tissue sarcomas (STS). MATERIAL AND
      METHODS: 146 STS samples were investigated by single strand DNA conformation
      polymorphism (SSCP)-sequencing for p53 mutations. Additionally, IHC with five p53
      antibodies (CM-1, Pab1801, Pab240, DO1, DO-7) was performed. RESULTS: In 65 to
      131 tumor samples (44.5% to 90.4%) elevated levels of p53 protein were recorded
      by IHC, depending on the antibody applied. Sixteen out of 146 STS tumor samples
      (11%) had p53 gene mutations. 13 cases (81.2%) of the 16 tumors with p53
      mutations could be detected by DO-1. However, of the 93 DO-1 positive tumors 79
      were negative by SSCP-sequencing analysis. Using multivariate regression analysis
      (Cox proportional hazards model) both p53 mutations (non-frameshift mutations)
      and IHC detection of p53 protein overexpression were prognostic predictors for
      poor survival. CONCLUSIONS: This study suggests that IHC is valuable for
      assessing p53 mutations in STS, but sequencing provides additional important
      information on the molecular characteristics of the alterations.

PMID- 9568076
TI  - Synthesis and biological activity of beta-ionone-derived alcohols for cancer
      chemoprevention.
AB  - Secondary products of plant mevalonate metabolism suppress the synthesis of
      mevalonate, the rate-limiting intermediate in the biosynthesis of isoprenoid
      derived compounds that stimulate cell proliferation. They exert their inhibitory
      action by the suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase (HMGR). They exhibit low toxicity and have proven their efficacy in
      animal cancer chemoprevention studies but their growth inhibitory activities
      leave room for improvement. We have chosen beta-ionone (1) as a lead compound for
      the development of more potent inhibitors of mevalonate pathways. A series of
      ionone-derived alcohols have been synthesized and tested on an in-vitro model
      system (B16F10 mouse melanoma). We have found several derivatives which show
      higher growth inhibitory properties and are promising candidates for further
      improvement of activity.

PMID- 9568077
TI  - Cloning of a human cancer cell line (NSCLC-N6) and comparative study of the
      clones in vitro.
AB  - Non-small-cell lung carcinoma (NSCLC) is a particularly serious disease because
      of its chemoresistance to current treatments. To investigate the nature of his
      generally innate resistance, we cloned an established cell line (NSCLC-N6)
      derived from a non-small cell bronchopulmonary carcinoma. Four cell
      subpopulations (C15, C65, C92 and C98) were isolated from the mother line. These
      four clones were studied in comparison with each other for cell doubling time in
      vitro, ploidy, chemosensitivity in vitro, cytogenetic, expression of the oncogene
      erb-B2 and other tumor markers (Kr, CEA and Chr A). Each clone shows a distinct
      biologic pattern for various biological parameters. Our results indicated hat
      cell doubling time (in vitro) increased when the hyperploid population was
      prevailing. The clones differ in their chemosensitivity to therapeutic agents.
      This cellular diversity might help to explain why these tumors are
      chemoresistant. This heterogeneity within NSCLC tumors should be taken into
      consideration in the choice of treatment.

PMID- 9568078
TI  - Prognostic aspects of the loss of epithelial basement membrane components in
      preinvasive and invasive laryngeal carcinomas.
AB  - The integrity of the epithelial basement membrane (BM) is an essential criterion
      or the biological behaviour of tumors. Previous studies on various types of
      carcinomas have demonstrated a good correlation between the amount of retained BM
      and the course of tumor growth. We therefore evaluated the prognostic
      significance of the tumor BM in laryngeal carcinomas. In this study, we analyzed
      66 cases of laryngeal carcinomas using immunohistochemistry for the visualization
      of the major BM components collagen IV and VII, laminin-1, heparan sulfate
      proteoglycan (HSPG, perlecan) and fibronectin. The extent of retained BM-material
      was quantified morphometrically. A subsequent statistical analysis correlated the
      immunohistochemical findings with clinical and routine histological parameters,
      such as the mode of tumor infiltration. All carcinomas showed a defective
      epithelial BM. In addition, we observed a correlation between the degree of tumor
      cell-differentiation and the amount of BM material retained. The loss of BM,
      however, affected the various components differently with an "early" loss of
      collagen VII. In non-infiltrative dysplastic lesions focal BM disruptions were
      seen which affected the various BM components very similarly. When we
      statistically analyzed the correlation between the BM staining pattern and
      prognostically relevant parameters, collagen VII represented a marker for "early"
      stroma invasion. It also positively correlated with tumor size/stage, presence of
      lymph node metastasis and the recurrence of tumor growth. The collagen IV
      expression was positively correlated with the degree of tumor cell
      differentiation. The other parameters did not show further prognostically
      relevant data. Our observations provide significant information on the biological
      course of the disease. Thus, collagen VII may be a marker for "early" invasive
      tumor growth, as well as for lymphatic metastasis and local tumor recurrence,
      while the amount of collagen IV correlates with the tumor cell differentiation.

PMID- 9568079
TI  - Effect of glucocorticoid hormone on nuclear matrix in cervical cancer cells in
      vitro.
AB  - Human papillomavirus (HPV) is one of the crucial factors in cervical
      carcinogenesis. High risk HPV16 prototype has been demonstrated in association
      with the nuclear matrix in a cervical carcinoma cell line(1,2). Nuclear matrix
      (NM) has been established as playing an important role in various nuclear
      activities as well as carcinogenic processes. Dexamethasone (DEX) (glucocorticoid
      hormone) inhibited the growth of CC2/CUHK2 cervical carcinoma cells with
      concurrent induction of epithelial cell differentiation. 2D- PAGE (IEF and
      NEPHGE) revealed alternations in NM protein composition. Further demonstration of
      changes in NM was evidenced by NuMA (a novel NM protein) labelling. The HPV16 E7
      oncoprotein was shown to be reduced in total cellular protein as well as in NM
      protein fractions in response to DEX treatment, and this suppressed expression
      was confirmed by RT-PCR. Thus, it is suggested that dexamethasone can down
      regulate the growth of cervical cancer cells and its induced changes in NM may be
      a cause of this suppression.

PMID- 9568080
TI  - Transcriptional regulation of retinoic acid responsive genes by cellular retinoic
      acid binding protein-II modulates RA mediated tumor cell proliferation and
      invasion.
AB  - The chemotherapeutic agent retinoic acid (RA) inhibits the proliferation and
      invasion of many tumor types. RA chemotherapy in head and neck squamous cell
      carcinoma (SCC) patients reduces recurrence and induces regression of
      premalignant lesions. The effects of RA are mediated by both cytoplasmic and
      nuclear proteins. In the nucleus, a family of ligand-dependent transcription
      factors, the retinoic acid receptors (RAR) and the retinoid X receptors (RXR),
      regulate target gene response to RA. In the cytoplasm, the cellular retinoic acid
      binding proteins I and II (CRABP) regulate intracellular RA concentration,
      transport, and metabolism. Alterations in CRABP expression have been shown to
      affect target gene response and the phenotype of cancer cells. To elucidate the
      role of these proteins in mediating the RA response, we examined target gene
      expression and malignant phenotype in SCC25 cells expressing an antisense CRABP
      II construct. RA induced CRABP II mRNA levels 2 fold in SCC25 cells by
      transcriptional upregulation. Expression of the antisense construct reduced CRABP
      II expression to undetectable levels. Inhibition of CRABP II expression resulted
      in significant downregulation of RA responsive genes. These reductions were the
      result of decreased transcription from RA responsive promoters. Surprisingly,
      clones expressing the antisense CRABP construct were less sensitive to RA
      mediated inhibition of proliferation. These clones were also less invasive in an
      in vitro invasion assay, likely due to downregulation of matrix metalloproteinase
      activity. We conclude that CRABP II affects the transcription of RA responsive
      genes which regulate proliferation and invasion of head and neck SCCs.

PMID- 9568081
TI  - Multiple synchronous colorectal carcinomas: a ploidy study by image analysis.
AB  - Cytometry could represent an ancillary technique to morphology in order to
      understand whether multiple synchronous colorectal carcinomas arose
      independently. Twenty-eight multiple synchronous tumours, assessed by means of a
      computerized image analysis system for DNA ploidy, were categorized as diploid
      (4) or not diploid (24). The ploidy classes were: DNA-diploid, DNA-tetraploid,
      and DNA-aneuploid. The DNA Index (DI) ranged from 0,90 to 2,66. The overall
      concordance rate for ploidy and DI class with synchronous tumours was 69% and
      31%, respectively. The high concordance rate in ploidic categories suggests the
      metastatic origin of our multiple synchronous tumours. Moreover, they showed
      site, Dukes' classification, degree of differentiation, percentage of ploidy
      class, and DI distribution comparable to the single colorectal carcinomas. In
      conclusion, image analysis is a reliable technique to determine the independent
      clonality or the common origin of multiple colorectal tumours when the evaluation
      based on the simple histopathological criteria is not satisfactory.

PMID- 9568082
TI  - Clinicopathologic differences between gastric remnant cancer and primary cancer
      in the upper third of the stomach.
AB  - BACKGROUND: The prognosis of gastric remnant cancer is considered to be poor
      compared with that of primary cancer. MATERIALS AND METHODS: This study was
      conducted to elucidate the differences of clinicopathologic findings and
      treatment results between 59 patients with gastric remnant cancer (GRC) and 579
      patients with primary proximal gastric cancer (PGC). RESULTS: There was no
      significant difference in the incidence of lymph node metastasis between GRC and
      PGC. However, changes in the metastatic pattern to lymph nodes were observed in
      GRC. In GRC, the tumor easily invaded the neighboring organs due to the adhesions
      around the remnant stomach, resulting in a low resectability with curative
      intent. The 5-year survival rate after curative resection for advanced GRC was
      50.9%. GRC patients without serosal invasion had a good prognosis. CONCLUSION:
      Although the survival rate after curative resection for GRC patients was similar
      to that of PGC, GRC patients without serosal invasion had a better prognosis.
      Therefore, early detection is an important way to improve overall survival in
      GRC.

PMID- 9568083
TI  - Correlation between p53 gene mutation, p53 protein labeling and PCNA expression
      in oral squamous cell carcinomas.
AB  - BACKGROUND: The prevalence of oral squamous cell carcinoma (OSCC) among the Black
      community in South Africa is unacceptably high. The association between p53
      protein, and PCNA overexpression and the presence of p53 gene mutations was
      evaluated. MATERIALS AND METHODS: One hundred and ten formalin-fixed, paraffin
      embedded blocks of OSCC were selected for immunohistochemical studies for p53
      protein and PCNA expression using the DO-7 and PC10 monoclonal antibodies,
      respectively. DNA was extracted from fifty-five blocks and exons 5 to 9 of the
      p53 gene were amplified with nested primers, thereafter sequencing was performed
      to confirm the presence of mutations detected by single stranded conformational
      polymorphism. RESULTS: Fifty-six cases (51%) showed p53 expression, while
      fourteen mutations (25%) were detected. A significant difference was found
      between the PCNA index in p53 positive and p53 negative tumors while the mean
      PCNA index for the tumors with p53 mutations was not significantly different from
      the tumors without mutations. CONCLUSIONS: No association between p53 protein
      overexpression and p53 gene mutations could be demonstrated.

PMID- 9568084
TI  - Biodistribution of 14C-misonidazole as a probe for hypoxic cells in a murine
      tumor model.
AB  - BACKGROUND: To evaluate potential of misonidazole (MISO) as a probe for hypoxia,
      the biodistribution of 14C-MISO was investigated in a murine tumor model.
      MATERIALS AND METHODS: Following intraperitoneal injection of 14C-MISO in C57BL/6
      mice with implanted meningial sarcoma tumors in the thighs, the animals were
      sacrificed at various times (0.5-120 hours), and 14C labeling was measured by a
      liquid-scintillation counter. The necrotic zone of tumor was identified by its
      appearance and separated from the non-necrotic tissue. RESULTS: Concentration
      time curves revealed a higher 14C label in the hypoxic areas, and the difference
      in 14C label between hypoxic and oxic areas widened as time elapsed. CONCLUSIONS:
      These results suggest that MISO bound the hypoxic cells more firmly, and the
      difference in 14C label reflects differences in the bioreductive ability of MISO
      in these cells. These promising results indicate the feasibility of MISO
      analogues as a non-invasive probe for hypoxic cell identification.

PMID- 9568085
TI  - Synergy of the combination of nedaplatin with etoposide in murine and human lung
      carcinoma.
AB  - BACKGROUND: The combination of cisplatin (CDDP) and etoposide (ETP) has been
      shown to be an effective treatment for lung cancer. Nedaplatin (NDP) has been
      developed as a second generation plainum complex. Because of its superior
      antitumor activity and lower nephrotoxicity in comparison with CDDP, the
      antitumor effects of NDP in combination with ETP against murine and human lung
      cancer was investigated. MATERIALS AND METHODS: Lewis murine lung carcinoma, RERF
      LC-AI, and Ma44 human lung cancer were used in this study. NDP (1/4 to 1 maximum
      to related dose; MTD) and CDDP (1/4 to 1 MTD) were administered once and ETP
      (1/32MTD) was administered daily for five days via the tail vein of mice.
      RESULTS: In the mice bearing Lewis lung carcinoma, a combination of NDP and ETP
      resulted in synergistically enhanced inhibition of tumor growth (Treated/Control
      ratio; T/C = 0.001) in comparison with either NDP or ETP alone (T/C = 0.12 for
      NDP, T/C = 0.13 for ETP), and prolonged survival (Increased Life Span; ILS% > or
      = 172) in comparison with either NDP or ETP alone (ILS% = 65 for NDP, ILS% = 54
      for ETP). NDP showed a more potent combination effect with ETP than CDDP did for
      both growth inhibition and survival. This effect was confirmed in human lung
      cancer. Although body weight loss was enhanced by the combined treatment, it was
      tolerable. With regards to myelosuppression, no significant difference between
      NDP plus ETP and CDDP plus ETP was observed. CONCLUSION: These results suggest
      the superiority of a combination of NDP with ETP against CDDP with ETP as a
      clinical therapy for lung cancer.

PMID- 9568086
TI  - Apoptosis induced by heavy ion (carbon) irradiation of two human tumours with
      different radiosensitivities in vivo: relative biological effectiveness (RBE) of
      carbon beam.
AB  - The effect of heavy ion (carbon beam) on apoptosis in vivo was studied. The human
      brain tumors xenografts of different radiosensitivities were used. The results
      demonstrated that the effect of carbon beam on apoptosis was similar to photon in
      radiosensitive tumors; however, carbon beam had the advantage on apoptosis in
      radioresistant tumors. In ependymoblastoma, a radiosensitive tumor, the incidence
      of apoptosis induced by photon and by carbon at 6 hours after irradiation were
      34.5 +/- 7.85% and 32.5 +/- 7.04%, respectively. In glioblastoma (radioresistant
      tumor), the incidence of apoptosis induced by photon and by carbon at 6 hours
      after irradiation were 1.35 +/- 1.68% and 4.4 +/- 2.47%, respectively. Therefore,
      the incidence of apoptosis was increased more than 3-fold (RBE 3.0) at 6 hours
      after irradiation in glioblastoma. The heavy ion (carbon) beam is effective in
      radioresistant tumors in vivo.

PMID- 9568087
TI  - Altered expression of integrins in adriamycin-resistant human breast cancer
      cells.
AB  - We investigated alterations in the expression of integrin on adriamycin-resistant
      MCF-7 (MCF-7/ADR) cells, which had been selected from MCF-7 human breast cancer
      cells, in order to examine the mechanisms behind the acquisition of malignancy in
      breast cancer progression. Expression of the alpha 6 integrin subunit of MCF
      7/ADR cells was stronger than that of MCF-7 cells, whereas expression of alpha 2
      integrin subunit of MCF-7/ADR cells was weaker than that of MCF-7 cells. MCF
      7/ADR showed increased binding activity to laminin, but not to collagen or
      fibronectin, compared to those of parental MCF-7 cells. Adhesion of MCF-7 cells
      to collagen and laminin was inhibited by the addition of antibody to alpha 2 and
      alpha 6 integrin subunit, respectively. On the other hand, adhesion of MCF-7/ADR
      cells to collagen was not inhibited by the addition of antibody to alpha 2, alpha
      3 or alpha 6 integrin subunit. Adhesion of MCF-7/ADR cells to laminin was
      inhibited by not only the antibody to alpha 6 subunit but also the antibody to
      the alpha 3 subunit. The transmigratory activity of MCF-7/ADR cells was higher
      than that of MCF-7 cells. A significant inhibitory effect on the transmigration
      of MCF-7/ADR cells was observed by the addition of antibody to alpha 6 and beta 1
      integrin subunit. MCF-7/ADR cells appeared smaller and flatter than MCF-7 cells,
      and spread to a greater extent on the culture dish. MCF-7 cells cultured on
      Matrigel for 24 hours formed clusters. In contrast to this, MCF-7/ADR cells
      expanded with a tubular-like pattern on Matrigel. The spread of MCF-7/ADR cells
      was incompletely inhibited by addition of the antibody to alpha 3 integrin
      subunit, and completely inhibited by addition of the antibody to alpha 6 and beta
      1 integrin subunit. These findings suggest that integrins on MCF-7/ADR cells are
      altered from those on parental MCF-7 cells in not only expression but also
      function, and that interaction between cancer cells and extracellular matrix
      protein is involved in augmentation of the invasiveness of MCF-7/ADR cells.

PMID- 9568088
TI  - Inhibition of xanthine oxidase by purpurogallin and silymarin group.
AB  - Thirteen phenolic compounds were tested for their inhibitory effects on xanthine
      oxidase. The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to
      xanthine and of xanthine to uric acid, which has lambda max of 295 nm, forming
      the basis for a spectrophotometric assay of the activity of xanthine oxidase. The
      results showed that purpurogallin and silymarin group displayed the inhibitory
      effects on xanthine oxidase (IC50 = 2.96 +/- 0.12 and 27.58 +/- 3.48 microM,
      respectively). Their apparent inhibition constants (Ki) were 1.16 and 5.85
      microM, and induced uncompetitive and mixed type (non-competitive-uncompetitive)
      inhibitions respectively, with respect to the substrate xanthine.

PMID- 9568089
TI  - Experimental observation of photochemically induced oxygen depletion in perfused
      cells undergoing photodynamic therapy.
AB  - This report presents a non invasive method for studying oxygen consumption during
      photodynamic therapy in cultured cells. The oxygen partial pressure of perfusion
      medium flowing through cells cultured on microcarrier beads, was investigated
      before, during and after treatment. Pheophorbide a was used as a sensitiser. Time
      dependent measurements demonstrate photochemical oxygen depletion induced by
      photosensitized reactions, followed by an oxygen pressure increase were
      attributed to a reduction in the cells' metabolism.

PMID- 9568090
TI  - Immune response of rat spleen cells to a carcinogen and to vaccination with anti
      p53 polyclonal antibodies.
AB  - BACKGROUND: The tumor-suppressive effects of rabbit anti-p53 antibodies on
      chemically induced rat colon cancer were demonstrated previously (Cancer J,
      10:116-120, 1997). METHODS: In this communication, the spleen's role in the
      immune response of rats to cancer and vaccination was evaluated histologically
      and immunohistochemically. The following groups of rats were studied: a) control
      non treated rats; b) tumor-free non vaccinated rats treated with a carcinogen; c)
      tumor-bearing non vaccinated rats; d) tumor-free vaccinated rats exposed to a
      carcinogen; e) tumor-bearing vaccinated rats. RESULTS: Exposure to a carcinogen
      (group 2) caused the appearance of the proliferative and apoptotic changes
      associated with immune response. They included abundant blast transformation of
      CD20-positive B lymphocytes, expansion of germinal centers and of periarterial
      sheaths (CD3-positive T cells), an increase in the number of plasma cells,
      mitotic and apoptotic cells in the follicles, and in CD25 IL2-depending T cells.
      The presence of colon tumors (group 3) caused insufficiency of the splenic
      lymphoid system: blast transformation was weaker, the white pulp area decreased
      and its devastation was reflected in fewer lymphoid cells. There were less plasma
      cells in the red pulp, while the number of dendritic cells, CD25+ T cells,
      macrophages and neutrophils increased sharply, suggesting a compensatory reaction
      to the severe antigenic effects. Similar, but stronger changes, occurred in tumor
      free vaccinated rats (group 4). In tumor-bearing vaccinated rats (group 5), the
      rate of proliferation change was higher than in group 3, probably as a result of
      a weaker splenic insufficiency. A strong correlation was found between the number
      of mitotic, apoptotic or dendritic cells, tumorigenesis and vaccination.
      CONCLUSIONS: A sharp increase in the number of dendritic cells in vaccinated
      tumor-bearing rats suggests that these cells participate in the host's reaction
      to tumorigenesis. We conclude that vaccination with anti-p53 polyclonal
      antibodies activates lymph components of the spleen.

PMID- 9568091
TI  - Red blood cell glutathione levels before and during treatment with neoadjuvant
      chemotherapy cisplatin/5-fluorouracil in patients with head and neck squamous
      cell carcinoma.
AB  - The purpose of this study was to find out whether the glutathione (GSH), in red
      blood cells could predict the response to neoadjuvant chemotherapy cisplatin/5
      fluorouracil (CDDP/5-FU) in patients with head and neck squamous cell carcinoma
      (HNSCC). Three courses of induction chemotherapy with CDDP/5-FU were administered
      and followed by surgery and radiotherapy or radiotherapy alone, in 51 patients
      with HNSCC. GSH was measured by spectrophotometry in red blood cell before any
      treatment (Sample 1: S1), after each course of chemotherapy (S2, S3, S4). Our
      results showed that GSH was the same at diagnosis in patients with complete or
      partial response (OR) compared to those with stable or progressive disease (NR).
      With regard to evolution of the GSH during the 3 courses of CT a significant
      difference was found between courses (S2: 5.06 +/- 0.35 vs S4 = 3.61 +/- 0.4
      mumol/g haemoglobin, p < 0.05). When we separated our patients into OR and NR, a
      significant difference was found over the 3 courses of chemotherapy for GSH
      content. Non responder patients showed decreased GSH content at the end of the
      treatment, (S2: 5 +/- 0.5 vs S4: 2.2 +/- 0.4 mumol/g haemoglobin, p < 0.05) while
      OR were stable. In conclusion, red blood cell GSH seems to have no early
      predictive value for chemoresponse to neoadjuvant chemotherapy CDDP/5-FU in
      HNSCC.

PMID- 9568092
TI  - Thyroid hormone depletion inhibits astrocytoma proliferation via a p53
      independent induction of p21 (WAF1/CIP1).
AB  - BACKGROUND: Clinical hypothyroidism has been associated with prolonged survival
      in several types of malignancies, but the mechanism of this effect is unknown.
      MATERIAL AND METHODS: In vitro studies of thyroid hormone depletion (via culture
      in medium containing 5% thyroid hormone-depleted fetal bovine serum (FBS)) were
      carried out using a human glioblastoma cell line (WITG3) which expresses a
      mutant, non-functional p53. RESULTS: Thyroid hormone depletion inhibited WITG3
      proliferation compared to control medium containing 5% euthyroid FBS. There was
      no evidence of apoptosis and viability was not compromised. Cell cycle analysis
      by flow cytometry indicated that thyroid hormone depletion accumulated WITG3
      cells in G1, with fewer cells progressing into S than in euthyroid medium. By
      immunoblotting, p21 (WAF1/CIP1) was only slightly detectable in lysates from
      WITG3 cells grown in control euthyroid medium; however, in thyroid hormone
      depleted FBS, a marked induction of p2 1 occurred which could be reversed by
      exogenous thyroid hormone CONCLUSIONS: These data indicate that thyroid hormone
      depletion may cause a G, arrest in astrocytoma mediated by a p53-independent
      induction of p21 (WAF1/CIP1). Results suggest a mechanism which may explain the
      effect of hypothyroidism on suppression of tumor cell growth.

PMID- 9568093
TI  - Modulation of cell rounding and apoptosis in trigeminal neurinoma cells by
      protein phosphatase inhibitors.
AB  - Exposure of trigeminal neurinoma 476-16 cells to C2-ceramide in a serum-deprived
      medium induces cell rounding followed by cell death characterized by cytoplasmic
      shrinkage and nuclear condensation. The induction of cell rounding and death
      occurs in proliferating cells but not in essentially quiescent cells of confluent
      cultures. Trypan blue-unpermeable round cells formed as a result of ceramide
      treatment undergo apoptosis without ceramide in a serum-containing medium,
      suggesting that they are irreversibly committed to cell death. The induction of
      cell rounding by ceramide is inhibited by low doses of the protein-tyrosine
      phosphatase inhibitors, orthovanadate and pervandate, and stimulated by high
      doses of pervanadate. The inhibition of protein-tyrosine phosphatases interfers
      the induction of cell death by ceramide. The protein-serine/threonine phosphatase
      inhibitor calyculin A induces cell rounding in proliferating cells. This cell
      rounding does not lead to cell death, thus calyculin A inhibits the induction of
      cell death by ceramide. While orthovanadate inhibits the induction of cell
      rounding by calyculin A, the latter is potentiated by ceramide. A combination of
      ceramide and calyculin A induces cell rounding and cell death in confluent
      cultures. These results demonstrate that modulation of phosphorylation of the
      serine/threonine and tyrosine of cellular proteins is intimately involved in the
      process of cell rounding and apoptosis in anchorage-dependent cells.

PMID- 9568095
TI  - Effects of radiotherapy and chemotherapeutic cytokines on a human salivary cell
      line.
AB  - BACKGROUND: Various malignancies are treated with radiotherapy or chemotherapy,
      or a combination of both. Unfortunately, these therapies also inflict damage to
      neighboring healthy tissues, such as salivary glands, during treatment for head
      and neck tumors. The purpose of this study was to evaluate the possible
      interaction between radiotherapy and chemotherapeutic cytokines [TNF-alpha and
      INF-gamma] on cell growth and survival, as well as IL-6 production in a human
      salivary cell line [HSG], and to examine the nature of salivary cellular death
      inflicted by the irradiation. RESULTS: A pronounced inhibitory effect on HSG cell
      growth was demonstrated 72 hours following treatment of the cells with TNF-alpha
      [10 u/ml] and INF-gamma [1000 u/ml] [69%, p < 0.01] or TNF-alpha [10 u/ml] and
      irradiation [15 Gy] [66%, p < 0.01]. This reduction in cell viability was
      accompanied by a pronounced increase in IL-6 production by the cells. Seventy-two
      hours post-irradiation [15 Gy], the HSG cell death rate was 70-75%, in agreement
      with a delayed salivary reproductive cell death model which could explain the
      life-long xerostomia which often results in head and neck irradiated patients.

PMID- 9568094
TI  - Alterations in focal adhesion and cytoskeletal proteins during apoptosis.
AB  - Ceramide induces cell rounding and subsequent apoptotic cell death in trigeminal
      neurinoma 476-16 cells. A protein tyrosine phosphatase inhibitor, orthovanadate,
      inhibits cell rounding and subsequent apoptotic death, while a serine/threonine
      phosphatase inhibitor, calyculin A, stimulates cell rounding but inhibits
      apoptosis (reference 11). In an attempt to determine critical cellular changes
      associated with cell rounding during the induction of apoptosis, focal adhesion
      and cytoskeletal proteins in apoptotic round cells induced by ceramide were
      examined by immunoblotting and compared with those of non-apoptotic round cells
      and adherent cells. As compared with adherent cells, tyrosine phosphorylation of
      a group of proteins between 110-125 KDa, including p125 focal adhesion kinase
      (FAK) is reduced in the apoptotic round cells as well as in non-apoptotic round
      cells induced by calyculin A and metaphase cells in mitosis. However, a concerted
      decrease of vinculin, paxillin and FAK, preceding the changes of whole cellular
      proteins, is seen in the apoptotic round cells but not in the non-apoptotic round
      cells. The inhibition of ceramide-induced apoptosis by orthovanadate is
      accompanied by a prevention of such a decrease in focal adhesion proteins. It
      thus appears that these focal adhesion proteins are degraded during the cell
      rounding occurring during apoptosis. Proteolysis of focal adhesion components may
      not only irreversibly disrupt cell adhesion but also impede transduction of
      growth and survival signals, and may play a critical role in the initiation and
      execution of apoptosis.

PMID- 9568096
TI  - Short- and long-term functional vs morphometrical salivary effects of irradiation
      in a rodent model.
AB  - BACKGROUND: Irradiation-induced salivary damage which results in severe
      xerostomia is a well known entity. However, the underlying mechanism of this
      phenomenon is still considered enigmatic. MATERIALS AND METHODS: We used one of
      the most studied models, male Wistar rats, and irradiated them to the head and
      neck region with both a low dose [2.5 Gy] and a high dose [15 Gy] of irradiation.
      Then we evaluated salivary gland function, weight and morphology of both parotid
      and submandibular glands in the same animals. Examinations were obtained for the
      short-term [3 days], long-term [40 days] and extended-term [90 days] time points.
      RESULTS: We found that irradiation with 15 Gy, but not 2.5 Gy, profoundly
      affected all salivary parameters evaluated, the parotid gland to a greater
      extent. At 40 days post- 15 Gy irradiation, parotid acini tissue was reduced by
      35% [p < 0.01], being replaced by fibrovascular stromal tissue. This reduction
      was accompanied by parotid weight and function reduction of 27% [p < 0.05] and
      58% [p < 0.01], respectively. At ninety days post-15 Gy irradiation, the parotid
      and submandibular functions were reduced by 84% [p < 0.01] and 62% [p < 0.01]
      respectively, while the gland weights were reduced by 62% [p < 0.01] and 39% [p <
      0.01], respectively. CONCLUSION: The accumulated data demonstrate the time and
      dose dependent effects of irradiation on both parotid and submandibular glands.
      The effects were more profound for the parotid gland and a partial correlation
      between salivary hypofunction and parenchymal destruction was demonstrated.

PMID- 9568097
TI  - Sensitivity of anticancer drugs in Saos-2 cells transfected with mutant p53
      varied with mutation point.
AB  - A human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53 gene,
      and clones of Saos-2 cells, which were transfected with wild type p53 or mutant
      p53 genes (123A, 143A, 175H and 273H), were observed for their surviving fraction
      after treatment with the commonly used anticancer drugs, cisplatin (CDDP),
      nimustine (ACNU), adriamicin (ADR) and bleomicin (BLM). The transfectants of the
      mutant 143A, 175H and 273H were significantly more resistant to CDDP than the
      transfectant of pOPI3 (expression plasmid only). The transfectants of the wild
      type p53 and mutant 123A were significantly more sensitive to ACNU than the
      transfectant of pOPI3. The transfectant of mutant 123A was more sensitive to ADR
      than the transfectant of pOPI3. There was no significant difference in
      sensitivity to BLM between Saos-2 and all kinds of transfectants. Thus the
      sensitivity of the cells to anticancer drugs varied with the mutation point of
      the p53 gene.

PMID- 9568098
TI  - Establishment of a liver metastatic model of human ovarian cancer.
AB  - We have established an in vivo experimental model in which human ovarian cancer
      grows in the ovary of nude mice and metastasizes to parenchymatous organs. An
      ovarian cancer cell line was orthotopically injected into the nude mouse ovary
      together with Matrigel by microsurgical techniques. The cells grew locally in the
      ovary and metastasized to the peritoneum, colon, omentum, liver, and spleen. When
      the cells were injected into the intraperitoneal cavity with Matrigel, they
      formed carcinomatous peritonitis but neither ovarian tumor formation nor the
      metastasis to parenchymatous organs was detected. Taken together, these findings
      indicate that the microenvironment of the ovary seems to be essential for
      metastasis of implanted human ovarian cancer cells. This in vivo experimental
      model allows us to investigate the mechanism of the metastasis of ovarian cancer,
      it will be also useful for the establishing a new therapeutic approach to
      preventing metastasis of human ovarian cancer to parenchymatous organs.

PMID- 9568099
TI  - Antitumor effect of human pancreatic cancer cells transduced with cytokine genes
      which activate Th1 helper T cells.
AB  - We have examined antitumor effect of human pancreatic carcinoma cells (AsPC-1)
      retrovirally transduced with interleukin-12 (IL-12), IL-15 or IL-18 gene in nude
      mice. The tumor growth of IL-12-expressing AsPC-1 cells was significantly
      retarded and that of IL-15-expressing cells was also impeded compared with that
      of wild-type cells, although their in vitro cell growth remained unchanged.
      However, the expression of IL-18 in AsPC-1 cells did not generate any antitumor
      effect since the tumor growth of the transduced cells was the same as that of
      wild-type cells. Thus, the differential actions of these cytokines on non-T cells
      can generate a variety of antitumor effect in nude mice, although their actions
      on T cells lineage favor the stimulation of Th1-type helper T cells.

PMID- 9568100
TI  - The primary in vitro anticancer activity of "half-mustard type" phenothiazines in
      NCI's revised anticancer screening paradigm.
AB  - Some new phenothiazines have been synthesized on the basis of previous studies.
      The anticancer activity of "half-mustard type" phenothiazines was investigated on
      sixty different cancer cell lines in vitro. The percentage of growth (PG), 50%
      inhibition of growth (GI50), the tumor growth inhibition (TGI) and the
      concentration required for 50% lethality of cells (IC50) were examined and
      calculated in the presence of various (from 10(-4) to 10(-8) M) concentrations of
      phenothiazine alkylurea derivatives. The following cell lines were involved in
      the study: 6 leukemia, 9 non-small-cell lung cancer, 7 colon cancer, 6 central
      nervous system cancer, 8 melanoma, 6 ovarian cancer, 8 renal cancer, 2 prostate
      and 8 breast cancer cell lines. The antileukemic activity of four chloroethyl
      substituted phenothiazine-alkylureas was shown by considerable growth inhibition,
      in the 10(-5) M range, of the six different leukemia cell lines. The 50%
      inhibition of growth was nearly the same for the four compounds on all cell
      lines. Tumor growth inhibition (TGI) and IC50 value to cells varied from -4.0 to 
      4.66. The two derivatives with the butylene bridge were more effective than
      propylene linked compounds against the CCRP-CEM, HL60 (TB), K-562 and MOLT-4 cell
      lines. However, the anti-leukemic activity of the derivatives was nearly the same
      for RPMT 8226 and SR cell lines. The substituent at the 2- position of
      phenothiazine ring and the length of the linker between the side chain nitrogen
      and the phenothiazine ring system are apparently important for antileukemic
      activity. Four of the 9 non-small-cell lung cancer cell lines were sensitive,
      while the other 5 cell lines were not. The compounds had a slight growth
      inhibitory effect on colon cell carcinoma and melanoma cells in which case the
      butylene linker seemed to be more effective than the propylene linker. At the
      same time, all of the compounds were weak or mostly inactive on cancer cells from
      the central nervous system. One ovarian cancer line of the 6, the IGROVI was
      sensitive to butylurea phenothiazines, however, the other five were not sensitive
      at all. The difference in the sensitivity of various renal cell carcinomas was
      significant: 5 lines were not sensitive, three of them (786-0, RXF-393 and TK-10)
      were sensitive to only butylene-substituted phenothiazine-ureas, propylene
      substitution resulted in ineffective compounds. The compounds were not able to
      inhibit the 2 prostate and 4 breast cancer cell lines, even at 10(-4) M. It was
      interesting that propylene-linked ureas were more effective than butylene-linked
      derivatives on MCF-7, but butylene-linked derivatives were more effective than
      propylene-linked compounds on MDA MB-231 and MDA-N. In addition, MDA MB 435 was
      more sensitive to the trifluoromethyl derivatives than the compounds without this
      substituent. Since the phthalimido-alkyl phenothiazines were not active at the
      first level of prescreen, these compounds were omitted from this study. The drug
      sensitivity of some cancer cell lines was not uniform for the different groups,
      therefore we postulate that the resistance can be related to some kind of
      (existing) drug-efflux mechanism. Apparently, the tumor specificity of
      phenothiazine alkylureas is more related to the leukemia specificity of
      alkylureas than to any CNS or lung specificity of phenothiazines.

PMID- 9568101
TI  - Microsatellite alterations in uterine leiomyomas.
AB  - Recent studies have shown that microsatellites instability (MI) has a leading
      role in the development of different types of cancer: a high rate of di-tri or
      tetranucleotide repeats have been found in familial polyposis and in sporadic
      colorectal, gastric, breast and endometrial carcinomas. In the present study, we
      selected the DNA of 23 histological samples from patients with uterine leimyomas,
      aged between 24 and 65 years. The negative portion was divided from the
      pathological portion in the same sample of each patient. Each sample was analyzed
      for 7 microsatellites (D25123, Mfd39, 635. 636. Mfd67, D11S905, SCZD1 and DM)
      through double amplification with the PCR using external and internal primer
      couples. Seven of 23 samples analyzed on the denaturant gel of acrylamide (30.4%)
      were positive for microsatellite alterations. The recurrence of these
      alterations, which appear in our study, suggest their involvement in benign
      transformation of smooth muscle cells.

PMID- 9568102
TI  - Hyaluronic acid binding capacity of malignant glioma cells.
AB  - The mechanisms underlying the rapid invasive growth of malignant gliomas are
      poorly understood. Adhesion to extracellular hyaluronic acid (HA) has been
      implicated in the invasive properties of tumor cells. We investigated the HA
      binding capacity of human (T98G, A172, U87MG, 86HG39, 85HG66) and rat (C6, 9L)
      glioma cell lines by means of HA coated, bovine serum albumin (BSA)-blocked
      (HA/BSA) and only BSA-blocked culture plates. Results were compared with adhesion
      to native wells (100% adhesion). Adhesion to HA/BSA was high for T98G (84.4%),
      medium for 86HG39 (36%), 9L (33.1%), A172 (35.5%) and low for 85HG66 (21.3%) and
      U87MG (26.8%). Adhesion to only BSA-coated wells was significantly lower in all
      these cell lines, suggesting a specific HA-adhesion. Only C6 showed similar
      adhesion to HA/BSA and BSA alone, therefore, C6 failed to bind HA specifically.
      These results suggest that adhesion to extracellular HA might be involved in the
      invasion of some gliomas.

PMID- 9568103
TI  - Effect of trichosanthin an anti-leukemia protein on normal mouse spleen cells.
AB  - Trichosanthin, from Trichosanthes kirilowii is a member of the Cucurbitaceae
      family. It has been reported to have anti-cancer activity. The effects of
      Trichosanthin peptides (15 amino acids in length) on ConA stimulated
      incorporation of 3[H] thymidine into cultured, primary mouse spleen cells and
      L1210 cells were determined. Both spleen cells and L1210 cells were plated at 7.5
      x 10(5) cells/ml in a microtiter plate. Different concentrations of the peptide
      (0.5, 5, 25, and 50 micrograms/ml) and ConA (1 microgram/ml) were added with
      serum free media, and half of the samples were labeled with 1 microCi/well of
      3[H] thymidine. The additional half of the cell samples were used to determine
      cell number and % viability. After 24 hours incubation, the N-terminal peptides
      (amino acid residues #1-15 and 16-30) caused increases in ConA stimulated
      incorporation of 3[H] thymidine into normal spleen cells at low concentrations of
      the peptides (5 micrograms/ml). The viability of spleen cells and L1210 cells
      were not affected by these peptides at 5 micrograms/ml. These N-terminal peptides
      (#1-15 and 16-30) were tested for in vivo anti-tumor activity. There was a delay
      of tumor formation in the treated vs control group. The results suggest that N
      terminal sequences of trichosanthin have anti-tumor activity.

PMID- 9568104
TI  - The effect of hyperbaric oxygen on growth and chemosensitivity of metastatic
      prostate cancer.
AB  - BACKGROUND: Currently, advanced prostate cancer (CaP) is not curable. In this
      report hyperbaric oxygen (HBO) is examined as an adjuvant to chemotherapy and as
      a stand-alone treatment. MATERIALS AND METHODS: CaP cell monolayers grown under
      normoxic conditions were exposed to cisplatin, taxol or doxorubicin for 90
      minutes under HBO (3.0 atmospheres, 100% O2) or normal pressure air. RESULTS: HBO
      reduced by 47% the concentration of doxorubicin required to produce a 20%
      reduction in cell numbers, but did not change the concentration required to
      produce a > 50% reduction. HBO increased the sensitivity of PC-3 cells to taxol
      at all concentrations, (mean 1.8%). Cisplatin chemosensitivity was not affected
      by HBO. HBO reduced the growth rate of DU-145 8.1% relative to control (p =
      0.01), and PC-3 2.7% (p = 0.12). CONCLUSIONS: This study shows that HBO can
      decrease the rate of growth, and increase sensitivity to anticancer agents,
      however, the effects are cell line dependent.

PMID- 9568105
TI  - Tempicol-2 (4-hydroxy-4-(2-picolyl)-2,2,6,6-tetramethylpiperidine-1-oxyl), a
      stable free radical, is a novel member of nitroxide class of antioxidants and
      anticancer agents.
AB  - As a part of our studies on the chemical, biochemical and pharmacological
      characteristics of the newly synthesized antioxidants, nitroxide derivatives, we
      designed a novel nitroxide, named Tempicol-2. Its capacity to act as antioxidant
      of potential pharmacological application was tested in three model systems:
      xanthine/xanthine oxidase, iron- and ascorbate Fenton reaction(s) and gamma
      radiolysis. The antioxidant properties of Tempicol-2 as a function of
      concentration were compared with those previously characterized nitroxide
      derivatives Tempace and Rutoxyl which we had synthesized. The possibility of one
      electron reduction of the novel substance by ascorbic acid was also examined and
      compared. The ability of Tempicol-2 to act as anticancer agent in vivo was also
      investigated in pharmacologic tests. The administration of Tempicol-2 to rats
      bearing 3 day-old Yoshida Sarcoma (promotion phase) led to both growth inhibition
      and the induction of apoptotic cells(s) death, comparable to the effects of
      Tempace and Rutoxyl under the same experimental conditions. Our results confirmed
      the suggested involvement of free radicals in the pathogenesis of model. Yoshida
      Sarcoma, thus indicating that anticancer activity of the investigated nitroxides
      may indirectly involve an antioxidant mechanism. The results reported here are
      encouraging as we find a limited correlation between the molecular redox
      properties, structure of nitroxides and their antitumor action. Tempicol-2,
      similarly to Tempace and Rutoxyl, is a promising antioxidant which can induce
      apoptosis, thus providing the basis for further investigations of the
      concentration and phase-dependent effects and the exact mechanisms of
      nitroxide(s) apoptotic action using cell line(s) model.

PMID- 9568106
TI  - Tumor cell membrane as a potential target for methyl-beta-cyclodextrin.
AB  - The purpose of this work was to determine the role of methyl-beta-cyclodextrin
      (MEBCD) in combination with doxorubicin (DOX) on DOX intracellular accumulation
      and efflux, in comparison to verapamil in a sensitive parental and multidrug
      resistant human cancer cell line (HL-60 S and HL-60 R). Moreover, cell membrane
      and nuclear modifications induced by MEBCD were investigated. At concentration of
      10 mumol for 10(6) cells, MEBCD combined with doxorubicin (DOX), was able to
      significantly enhance the intracellular concentration of DOX in HL-60 S and HL-60
      R cell lines during the period of exposure. In the resistant subline, MEBCD
      activity was higher than that of verapamil. Moreover, treatment of cells with
      MEBCD resulted in a modification in cell membrane integrity and cell morphology,
      but had no own activity in the distribution of the cells within cell cycle.

PMID- 9568107
TI  - Modulation of elongation factor-1 delta (EF-1 delta) expression by oncogenes in
      human epithelial cells.
AB  - A cDNA clone covering part of the C-terminal domain of human EF-1 delta was
      isolated from mammary cancer cells by subtractive hybridisation. The higher
      expression of EF-1 delta in the tumours suggested that malignant transformation
      in vivo requires an increase in translation factor mRNA and protein synthesis for
      entry into and transition through the cell cycle. To explore the relation between
      cell division and EF-1 delta expression, MCF-7 cells were treated with
      dexamethasone, an inducer of differentiation. There was no change in the mRNA
      levels of EF-1 delta in the dexamethasone-treated cells. To explore the relation
      between oncogenes and EF-1 delta expression, a variety of oncogenes were
      introduced into human mammary epithelial cells (MCF-7) and human keratinocytes
      (HaCaT). Despite high oncogene mRNA expression, there was no significant change
      in the EF-1 delta mRNA level by v-src, c-erbB (EGF Receptor), c-erbB-2, v-myc and
      v-fos oncogenes. However, overexpression of v-Ha-ras in HaCaT cells resulted in a
      three to five-fold decrease in the steady-state mRNA level of EF-1 delta. Taken
      together, the data provides further support on the interaction of translation
      factors and oncogenic transformation.

PMID- 9568108
TI  - Characterization of canine MDR1 mRNA: its abundance in drug resistant cell lines
      and in vivo.
AB  - BACKGROUND: Overexpression of the MDR1 gene often contributes to antineoplastic
      drug resistance. The purpose of this study was to characterize the canine MDR1
      mRNA homologue and evaluate its expression in both canine cell lines and
      lymphomas. MATERIALS AND METHODS: The abundance of the canine MDR1 transcript was
      assessed in three resistant cell lines and in pretreatment canine lymphoma using
      semi-quantitative RT/PCR. RESULTS: Canine transcript was 4.5 Kb with 93% sequence
      homology to human MDR1, and 90% homology to mouse and hamster equivalent genes.
      Increase in MDR1 transcript levels was observed in three progressively resistant
      canine cell lines. De novo MDR1 transcript expression was independent of response
      to therapy in dogs with lymphoma. CONCLUSIONS: We conclude that the canine MDR1
      mRNA homologue is structurally similar to the human transcript. Expression of
      MDR1 mRNA correlates with in vitro drug sensitivity but does not correlate with
      in vivo doxorubicin sensitivity in canine lymphoma.

PMID- 9568109
TI  - Antitumor effect of polysaccharide coated liposomal adriamycin on AH66 hepatoma
      in nude mice.
AB  - Drug delivery systems play a crucial role in cancer chemotherapy, not only in the
      achievement of sufficient tumoricidal effect but also in minimizing systemic side
      effects. We investigated the effect of liposomal adriamycin with tumor
      recognition molecule, 1-aminolactose (1-AL), on AH66 hepatoma transplanted into
      nude mice. Adriamycin (ADM) was encapsulated in liposome coating with cholesterol
      pullulan (CHP) to increase the stability in the blood stream. 1-AL was assembled
      to the outer layer of CHP-coated liposomal ADM as a tumor recognition molecule.
      In an in vivo therapeutic study. 1-AL/CHP-coated liposomal ADM restrained tumor
      growth more when compared with CHP-coated liposomal ADM. Thus, 1-AL/CHP-coated
      liposome seems to be a carrier of ADM to tumor cells.

PMID- 9568111
TI  - Modification of growth in small heat shock (hsp27) gene transfected breast
      carcinoma.
AB  - The role of hsp27 in the regulation of cell growth has been investigated in the
      breast cancer cell line MDA-MB-23 1. Cells were co-transfected with an expression
      vector carrying the human hsp27 gene (pSG-2711) and a plasmid conferring neomycin
      resistance (pWlneo). Transfected cells were selected for neomycin resistance.
      Stable transfectants were used as a pooled population for further experiments,
      since single-cell colonies were not able to grow into mass culture under
      continuous selection pressure. Over-expression of hsp27 was analysed by
      immunohistochemistry and immunoblotting. Cells only transfected for neomycin were
      used as control cells. The growth rate of the transfected cell line was
      determined whether overexpression of hsp27 directly influences the growth
      properties of the cells. Growth analysis of transfected cell lines in vitro
      revealed a lower proliferation rate of the hsp27 overexpressing cells compared to
      controls. These data suggest that hsp27 is involved in downregulation of cell
      proliferation in this human breast cancer cell line.

PMID- 9568110
TI  - Enhancement of anticancer effects of radiation and conventional anticancer agents
      by a quinolinone derivative, vesnarinone: studies on human gastric cancer tissue
      xenografts in nude mice.
AB  - Vesnarinone (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-
      quinolinone), a quinolinone derivative, is an orally active inotropic agent used
      in Japan for the treatment of chronic heart failure. Recently, it has been
      reported that vesnarinone induces differentiation and apoptosis in certain types
      of leukaemia and solid tumour cells, and exhibits antitumour effect on several
      tumours xenografted in nude mice. In the present study, we examined the
      antitumour effect of vesnarinone in combination with radiation and conventional
      anticancer agents in nude mice xenografted with human gastric carcinoma, a poorly
      differentiated adenocarcinoma, MKN-45 cell line which has a wild-type p53 gene.
      Vesnarinone treatment combined with radiation resulted in a higher antitumour
      activity compared with a single treatment with either vesnarinone or radiation
      alone. Further, vesnarinone treatment together with radiation and conventional
      anticancer agents including 5-FU and picibanil (an immunopotentiator) produced
      the highest antitumour effect compared with any other treatment. Additionally,
      the combination treatment induced marked differentiation and apoptosis of the
      tumour cells and an increase in the expression of p53 gene in the treated tumour
      cells. The results suggest that vesnarinone, in combination with radiation and
      the conventional antitumour agents, may be of clinical interest for treatment of
      certain types of gastric tumours.

PMID- 9568112
TI  - Inactivation of bone marrow cultures and K562 leukaemic cell line by Mossbauer
      effect.
AB  - Bone marrow cells collected from normal donors and from patients with chronic
      myelogenous leukemia (CML) and cultures of the K562 leukaemic cell line, were
      investigated after treatment with hematin and low-energy gamma rays from a 57Co
      Mossbauer source. Different degrees of growth inhibition were observed for bone
      marrow cultures and for the leukaemic cell line K562. Exposure to light
      irradiation during sample treatments was also investigated. The results seem
      promising and it is author's belief that cell inactivation by Mossbauer effect
      could have future applications in the field of tumor pathology as an alternative
      to or in the support of conventional radiotherapy.

PMID- 9568113
TI  - Interaction between eugenol-related compounds and radicals.
AB  - The radical modulating activity of 2-methoxy-4-(2-propenyl)phenol (eugenol), 2-t
      butyl-4-methoxy-phenol (BHA), and their dimers (bis-eugenol, bis-BHA) was
      investigated, using ESR spectroscopy. Eugenol produced radicals in alkaline
      solutions, and enhanced the radical intensity of both sodium-L-ascorbate and
      sodium 5,6-benzylidene-L-ascorbate. BHA has similar, but slightly lower activity,
      and their dimers were inactive. Their ability to scavenge the superoxide anion
      (O2-), generated by hypoxanthine and xanthine oxidase reaction, was in the order
      of eugenol > bis-eugenol > BHA > bis-BHA. The relative radical intensity among
      these compounds was paralleled by their cytotoxic activity. The present study
      demonstrates that eugenol and BHA were very reactive with radicals and their
      reactivity was considerably reduced by dimerization. The applicability of the
      dimerized eugenol in dentistry was discussed.

PMID- 9568114
TI  - Radical productions and pi-spin density by UHF/PM3 method on benz[c]acridines and
      benzo[a]phenothiazines.
AB  - On the calculated pi-spin density (rho pi) of benz[c]acridines [1-12],
      benz[c]acridines [2,8-12] with alternately value of pi-spin density (rho pi) on
      angular ring, large negative pi-spin density at C-1 and C-3 positions and large
      positive pi-spin density at C-2 and C-4 positions indicates their
      carcinogenicity, except for 7-methylbenz[c]acridine [7]. Benz[c]acridines [1,3-6]
      which do not follow were not carcinogenic. Radical producing
      benzo[a]phenothiazines [13-16] and non-radical producing benzo[a]phenothiazines
      [17-19] gave calculated pi-spin density (rho pi) which was positive in radical
      producing benzo[a]phenothiazines [13-16] at N-12 position, and had the opposite
      pi-spin density in non-radical producing benzo[a]phenothiazines [17-19].

PMID- 9568115
TI  - Growth curves: a method of monitoring established long-term primary human tumor
      cell cultures for autologous immunotherapy.
AB  - Cytomorphologic methods evidentiate tumor cells (TC) and differentiate them from
      fibroblasts, but are not indicated f for long term cultures. Growth rate and
      curve shape of TC and autologous fibroblasts cultures were recorded and compared
      over 4 weeks. Both were morphologically documented ex vivo and after MGG stain.
      No fibroblast overgrowth was noted in the TC cultures. The cultures showed rather
      peculiar curves with little variability among TC cultures. The 1st-week rate was
      higher in the TC cultures (p < .01). Growth curve evaluation with ex vivo
      observation of the morphology is- an alternative method in monitoring TC cultures
      for autologous immunotherapy.

PMID- 9568116
TI  - Suppression of growth of Bomirski Ab melanoma and its metastasis in hamsters by
      angiogenesis inhibitor TNP-470.
AB  - The growth of solid tumors and their metastasis is dependent on the development
      of new blood vessels (angiogenesis). In this study, we examined the effect of the
      angiogenesis inhibitor TNP-470 on a fast growing melanoma in hamsters. The effect
      was observed both on tumor growth and metastasis. Treatment with TNP-470 caused a
      significant decrease in the rate of tumor growth and suppression of the
      development of metastasis in 63% of treated animals. Some of the hamsters treated
      with TNP-470 had the tumor excised and the effect of that operation on the
      development of metastasis was examined. In such cases the inhibitory effect of
      TNP-470 was weaker than in tumor bearing animals. This indicates that excision of
      tumor created more favourable conditions for angiogenesis and that the dose of
      TNP-470 should be increased to be effective in such conditions.

PMID- 9568117
TI  - Effect of 7,12-dimethylbenz(a)anthracene on onco/suppressor gene action in vivo:
      a short-term experiment.
AB  - Dimethylbenz[a]anthracene is a pluripotent carcinogenic chemical, which acts as
      an initiator by causing point mutations in certain oncogenes and tumor suppressor
      genes. Changes in their expression may be another possible area of investigation
      the carcinogenic effect of DMBA. Elevated expression of oncogenes was previously
      has been shown after treatment with carcinogenic compounds. In the present study,
      expression of c-myc, c-Ha-ras and p53 24 hours after a single dose treatment of
      DMBA in the spleen and in the liver of Long-Evans rats was investigated. Control
      animals were injected with the solvent corn oil only. We could not find any
      significant change on the transcriptional level of the investigated oncogenes in
      the liver. In the spleen, the overexpression of Ha-ras was 2-fold and c-myc was 3
      fold higher in the DMBA-treated rats than in the corresponding control group.
      Since DMBA is a typical environmental carcinogen, the results of animal
      experiments may serve as a basis for application of gene expression
      investigations as a screening method in humans.

PMID- 9568118
TI  - Genotoxicity of polycyclic musk fragrances in the sister-chromatid exchange test.
AB  - The synthetic polycyclic musk fragrance compounds Galaxolide (1,3,4,6,7,8
      hexahydro-4,6,6,7,8,8-hexamethyl-cyclo-penta-(g)-2-++ +benzopyrane, Tonalide (7
      acetyl-1,1,3,4,4,6-hexamerthyltetraline), Celestolide (4-acetyl-1,1-dimethyl-6
      tert, butylindane), Phantolide (6-acetyl-1,1,2,3,3,5-hexamethylindane), Cashmeran
      (6,7-dihydro-1,1,2,3,3-pentamethyl-4-(5H) indanone) and Traseolide (5-acetyl
      1,1,2,6-tetramethyl-3-isopropylindane) are widely used as fragrance ingredients
      in perfumes, lotions and detergents; as food additives in cigarettes and fish
      baits. Several studies identified polycyclic musk fragrances in aquatic
      environment samples, human milk and human adipose tissue as highly lipophil with
      human lymphocytes.

PMID- 9568119
TI  - Loss of heterozygosity of chromosome 9p21 and 7q31 is correlated with high
      incidence of recurrent tumor in head and neck squamous cell carcinoma.
AB  - To examine whether genetic factors influence the prognosis of cancer patients,
      several polymorphic markers were used to determine the allelic loss of certain
      areas of the genome. Two polymorphic markers, IFNA and D9S171 were used to study
      the loss of heterozygosity (LOH) of chromosome 9p21 in 75 head and neck squamous
      cell carcinomas. LOH was detected in 14 out of 64(22%) DNA samples obtained from
      cancer specimens when at least one marker was used. The frequency of LOH was not
      correlated with the localization of the tumor, clinical stage of the patient,
      tumor size and lymph node involvement. However, the frequency of LOH was
      significantly higher in the recurrent tumors than in the non-recurrent tumors,
      suggesting that the allelic loss at 9p21 can be correlated with the short term
      prognosis of the patients. LOH was identified in only three out of 19(16%)
      samples when D7S522 was used as a marker. However, all of these three cases were
      recurrent, and two of the three showed the allelic loss at 9p21 at the same time.
      These results indicate that LOH of 9p21 and/or 7q31 is a novel prognostic factor
      independent of other clinical factors for head and neck squamous cell carcinoma.
      Replication error (RER) was observed in 4 cancers, implicating genetic
      instability in the carcinogenesis of a subset of head and neck squamous cell
      carcinoma.

PMID- 9568120
TI  - Inhibition of actin polymerization by cytochalasin B induces polyploidization and
      increases the number of nucleolar organizer regions in human megakaryocyte cell
      lines.
AB  - Megakaryocyte polyploidization is an advantageous and regulated mechanism which
      leads to an increase in platelet production. In megakaryocyte cell lines,
      polyploidization can be obtained by using cytochalasin B, an inhibitor of the
      actin polymerization. The Nucleolar Organizer Regions (AgNORs) are parts of
      nucleolar DNA transcribed into ribosomal RNA. They are detected by silver
      staining technique and their number is proportional to protein synthesis. In
      order to estimate protein synthesis in polyploidizing megakaryocytes, AgNORs were
      measured in three cell lines with megakaryocyte properties (DAMI, HEL and K562)
      after a 4-day culture in the presence or absence of cytochalasin B, an inhibitor
      of the actin polymerization. The mean number of AgNORs per cell was 16.4 +/- 4.3
      (m +/- SEM); 24.4 +/- 2.5 and 13.6 +/- 3.1 for DAMI, HEL and K-562 cell lines,
      respectively. The addition of cytochalasin B (2 micrograms/ml) increased
      significantly the number of AgNORs per cell (DAMI: 437%, HEL: 384% and K-562:
      345% of controls, p < 0.05 by t-test). Moreover, the numbers of nucleoles per
      cell after addition of cytochalasin B were augmented significantly (DAMI: 258%,
      HEL: 271% and K-562: 264% of controls, p < 0.05 by t-test). The total protein
      content estimated by Bradford's method increased significantly to 938%, 326% and
      388% of controls in DAMI, HEL and K562, respectively (p < 0.05 by t-test) in
      cells where actin was inhibited by cytochalasin B. In the presence of
      cytochalasin B, the endomitotic index (EI) [mean of (log2 DNA content expressed
      in N) 1] measured by flow cytometry increased to 368%, 207% and 538%, for DAMI,
      HEL and K-562 cell lines, respectively (p < 0.05 by t-test) after treatment with
      cytochalasin B. In contrast, the number of AgNORs per unit of DNA (EI) and the
      total protein content per unit of DNA did not change for DAMI, HEL and K-562 cell
      lines (p < 0.05 by t-test) after treatment with cytochalasin B. In conclusion,
      the increase in the number of the Nucleolar Organizer Regions by an agent known
      to stimulate polyploidization of megakaryocytic cell lines suggests that
      polyploidization occurs by enhanced protein production proportionally to DNA
      synthesis.

PMID- 9568121
TI  - Glycosylated antitumor ether lipids are more effective against oncogene
      transformed fibroblasts than alkyllysophospholipids.
AB  - We have investigated the antiproliferative effects of different types of
      antitumor ether lipids (AELs) against non-transformed and transformed
      fibroblasts. The compounds examined were choline phosphate-containing
      alkyllysophospholipids (1-O-octadecyl-2-O-methyl glycerophosphocholine (ET18
      OCH3), 2'-(trimethylammonio)ethyl 3-(hexadecyloxy)-2
      (methoxymethyl)propylphosphate (oxo-BM 41.440), 2'-(triethylammonio)ethyl 4
      (hexadecyloxy)-3-methoxybutane phosphonate (ET16-OCH3-phosphonocholine)), and
      glycosylated ether-linked diglycerides (1-O-hexadecyl-2-O-methyl-3-S-(beta-D-1'
      thioglucopyranosyl-sn-gly cerol) [ET16-OCH3-beta-thio-Glc] and 1-O-hexadecyl-2-O
      methyl-3-O-(2'amino-2'-deoxy-beta-D-glucopyranosyl)-sn -glycerol (ET16-OCH3
      Gln)). The choline phosphate-containing alkyllysophospholipids (ALPs) had little
      or moderate effect on the proliferation and none on the viability of NIH 3T3
      clone 7, and sublines transformed by raf (NIH/9IV #5), fes (Fes 1), src (Src 1)
      and mos (Mos 1) oncogenes. The glycosylated ether-linked diglycerides were more
      effective than the choline phosphate-containing ALPs. Of the two ether-linked
      diglycerides, ET16-OCH3-beta-thio-Glc did not affect the viability of the cells
      at any of the concentrations examined while ET16-OCH3-Gln was cytotoxic to all
      the transformed cell lines at concentrations equal to or greater than 9 microM.
      The IC50 for ET16-OCH3-Gln was 6.4 microM for Mos 1, 6.5 microM for NIH/9IV #5,
      7.5 microM for Src 1, 8.2 microM for Fes 1 and 8.4 microM for NIH 3T3 clone 7.
      These results suggest that the ether-linked diglycerides may be more effective
      against fibrosarcomas than the cholinephosphate containing ALPs. Also, with the
      exception of ET16-OCH3-Gln there was no significant difference in the effect of
      the compounds on the transformed and untransformed cell lines, suggesting that
      the selectivity displayed by AELs may depend on both the type of compound and
      transformation in the cell.

PMID- 9568122
TI  - beta-Sitosterol inhibits growth of HT-29 human colon cancer cells by activating
      the sphingomyelin cycle.
AB  - The present study examined the SM cycle as a mechanism to explain the inhibitory
      effect of SIT on HT-29 cell growth. SIT was the main phytosterol in the diet.
      Supplementation of SIT at 16 microM for 5 days in the media inhibited growth by
      55% as compared to cholesterol. SIT supplementation had no effect on sphingosine
      production. Ceramide production increased 45% with SIT supplementation as
      compared to cholesterol. Sterol supplementation had no effect on phospholipase C,
      a key enzyme in the PKC pathway. We concluded that the activation of the SM cycle
      may play a role in growth inhibition of HT-29 cells by SIT.

PMID- 9568123
TI  - Fine needle aspiration of the breast: a practical approach to diagnosis of
      carcinoma.

PMID- 9568124
TI  - Fine needle aspiration of the breast. A probabilistic approach to diagnosis of
      carcinoma.
AB  - OBJECTIVE: To develop a classification scheme for reporting the results of fine
      needle aspiration (FNA) cytology of a breast lesion according to its likelihood
      of being a carcinoma. STUDY DESIGN: To verify the validity of this scheme, we
      studied a total of 267 FNAs that were prospectively classified according to
      predefined criteria as positive (76), suspicious (41), proliferative with atypia
      (66), proliferative without atypia (48) and unremarkable (36), and compared these
      results with the final histology. RESULTS: The percentages of patients who had
      carcinoma on histology were 100% (76), 93% (38), 35% (23), 6% (3) and 31% (11) of
      cases diagnosed as positive, suspicious, atypical proliferative, proliferative
      without atypia and unremarkable on cytology, respectively. However, if only
      invasive carcinoma is considered, then the percentage of carcinoma was 99% (75),
      93% (38), 23% (15), 2% (1) and 11% (4), respectively. The only invasive carcinoma
      in the proliferative-without-atypia category was a tubular carcinoma and
      represented a false negative diagnosis. All four invasive carcinomas with an
      unremarkable cytologic diagnosis were due to sampling errors. Definitive surgery
      after FNA was common in cases with positive (65%) and suspicious (42%) cytologic
      diagnosis, whereas all but one patient with atypical, proliferative and
      unremarkable diagnoses had a biopsy initially. CONCLUSION: This scheme of
      reporting breast FNA results with defined criteria according to the probability
      of identifying carcinoma provides a rational basis for guidelines for the
      management of breast lesions.

PMID- 9568125
TI  - Significance of cell groups in voided urine.
AB  - OBJECTIVE: To determine the significance of different types of cell groups in
      voided urine for diagnosing transitional cell carcinoma (TCC). STUDY DESIGN: We
      reviewed voided urine specimens, with corresponding biopsies taken within 120
      days after urine collection, for cell groups. Type and number of cell groups were
      correlated with the histologic diagnoses. RESULTS: Of 5,001 voided urine
      specimens, 134 (3%) had corresponding biopsies. Flat sheets were significantly
      more common in urine specimens with corresponding negative biopsies (24%) than in
      those with biopsies showing TCC (6%) (chi 2 P = .0032). The incidence of
      collared, three-dimensional cell groups was low (0-7%) and not associated with
      biopsy findings. Irregular, three-dimensional cell groups were more common than
      collared cell groups and were most common in cases with invasive TCC on biopsy
      (38%). While this was statistically significantly more common than in urines
      associated with negative biopsies (17%) (chi 2 P = .0499), it was not specific.
      Requiring three or more irregular cell groups did not improve discrimination
      between TCC and benign cases. Cell groups of any type or number were not more
      common in cases associated with grade 1 papillary TCC than negative biopsies.
      Diagnoses associated with multiple irregular, three-dimensional cell groups and a
      negative biopsy included medullary sponge kidney, hemorrhagic cystitis, cystitis
      not otherwise specified, and urolithiasis. CONCLUSION: Irregular, three
      dimensional cell groups were most common in voided urine from patients with
      invasive TCC, but the identification of cell groups of any type in voided urine
      had little diagnostic utility.

PMID- 9568126
TI  - Mass screening for cancer of the endometrium in Miyagi Prefecture, Japan.
AB  - OBJECTIVE: To survey the results of mass screening for cancer of the endometrium
      performed over a six-year period in Miyagi Prefecture, Japan. STUDY DESIGN:
      Materials were cytodiagnostic samples of the endometrium examined by the Miyagi
      Cancer Society. The samples were classified into two groups: The mass screening
      group, from whom samples were collected according to the Health and Medical
      Service Law for the Aged, and the outpatient group, consisting of samples from
      other patients. The rates of subjects judged to require close examination and the
      detection rate of cancer of the endometrium in the two groups were compared.
      RESULTS: In the mass screening group, the rate of subjects judged to require
      close examination and the detection rate of cancer of the endometrium were 2.3%
      and 0.11%, respectively, while they were 5.9% and 0.39%, respectively, in the
      outpatient group; the differences between the two groups were significant.
      CONCLUSION: To improve the detection rate in mass screening for endometrial
      cancer according to the Health and Medical Service Law for the Aged, it is
      necessary to establish a new criterion for selecting subjects.

PMID- 9568127
TI  - Mass screening for cancer of the uterine cervix in Miyagi Prefecture, Japan.
      Effects and problems.
AB  - OBJECTIVE: To evaluate the effects of and problems with mass screening and in
      Miyagi Prefecture, Japan. STUDY DESIGN: About 3,570,000 females who underwent
      mass screening for cervical cancer between 1962 and 1994. RESULTS: The screening
      rate in the female population aged 30 years or older was 9.5% in 1970, gradually
      increased and exceeded that rate in 1991 but showed only slight changes
      thereafter. The standardized death rate due to malignant neoplasm of the cervix
      fell from 12.1 per 100,000 in 1961 to 4.0 in 1994. CONCLUSION: There still remain
      various problems, such as lack of a further increase in the screening rate, the
      fixation of examinees and an increase in the incidence of cervical cancer in
      young females.

PMID- 9568128
TI  - Relative value and cost-effectiveness of culture and special stains in fine
      needle aspirates of the lung.
AB  - OBJECTIVE: To define the role of microbiologic stains and culture in lung fine
      needle aspiration (FNA) specimens. STUDY DESIGN: All lung FNA specimens over a
      nine-year period, with results of both culture and microbiologic stains (Gram's,
      methenamine silver and acid fast) were reviewed and correlated with clinical
      information. RESULTS: Sixty-five cases were identified; 13 cases represented
      clinically significant infections (20%). Gram's stain identified 3 infections and
      had 1 false positive result, while culture identified 7 infections and had 9
      false positive results. However, all false positive cultures represented easily
      identifiable contaminants, and eight of nine cases had no associated acute
      inflammation or necrosis. Aspergillus species were detected in four cases by
      Papanicolaou and silver stain, while culture was positive in only one case.
      Coccidioides immitis was detected by both Papanicolaou stain and culture in one
      case. A single case of Mycobacterium tuberculosis was identified by both culture
      and acid-fast stain. While culture appeared more cost-effective than Gram's stain
      for identifying bacteria, both Papanicolaou and methenamine silver stain were
      more cost-effective for identifying fungi. CONCLUSION: In lung FNA specimens,
      culture and special stains should be restricted to specimens with acute
      inflammation or necrosis. Gram's stain and fungal culture are insensitive and not
      cost-effective, and fungi are often identifiable with routine stains.

PMID- 9568129
TI  - Testicular leukemia relapse. Fine needle aspiration findings.
AB  - OBJECTIVE: To study the role of testicular fine needle aspiration (FNA) in the
      diagnosis of leukemia relapse. STUDY DESIGN: The study group consisted of 32
      leukemia patients in complete remission for one to five years. Their ages ranged
      from 8 to 63 years. Twenty-five of them had bilateral testicular enlargement, and
      seven had unilateral enlargement. Hematologic workup and bone marrow studies of
      all of the patients showed no evidence of leukemia (full remission). FNA smears
      were obtained by using 22-gauge needles fitted to 20-mL syringes. RESULTS: The
      smears revealed 13 cases of acute lymphoblastic leukemia L2 (ALL-L2), 8 of ALL
      L3, 5 of acute monoblastic leukemia M5 (AML-M5), 1 of acute promyelocytic
      leukemia (APL-M3), 1 of AML-M1; 1 of erythroleukemia, AML-M6, 1 of chronic
      lymphocytic leukemia, 1 of chronic myelogenous leukemia and 1 of plasma cell
      leukemia. CONCLUSION: FNA study of the testis is safe, time saving, rapid and
      easy to perform for the diagnosis of testicular leukemia relapse, obviating the
      need for biopsy.

PMID- 9568130
TI  - Nuclear protrusions in cells from cytologic specimens. Mechanisms of formation.
AB  - OBJECTIVE: To explore the mechanisms of formation of nuclear protrusions (NPs)
      encountered in cytologic specimens and specifically the possibility of their
      being the result of an aberrant division of the cell and to determine how
      widespread the NP phenomenon is in cells from various tissues. STUDY DESIGN: Six
      hundred fifty-four cervical smears out of 5,000 with abundant cervical columnar
      epithelium examined were found to have many cells with NPs (group A). These cells
      were studied: (A) by light microscopy to define the structure and stages of
      formation of NPs, (B) by transmission electron microscopy (TEM), (C) by tubulin
      immunostaining for detection of mitotic spindle-associated microtubular
      structures, (D) by fluorescence in situ hybridization (FISH) utilizing X
      chromosome probes to monitor chromosomal movement into NPs, and (E) by direct
      fluorescence microscopy to examine autofluorescence patterns in cells with NPs.
      Also, tissue sections of 240 cervical cone biopsies, many including
      intraepithelial neoplasia (group B), were examined for NPs, and sections
      containing NPs were subjected to TEM. Last, 390 nongynecologic cytologic
      specimens from various lesions and organs obtained by fine needle aspiration or
      brushing methods were examined for the presence of NPs. RESULTS: NPs were found
      in a variety of tissues, epithelial and nonepithelial. Their formation in the
      cases examined appeared to be related to cell division, as indicated by: the
      light microscopic findings; the TEM findings (centriole at their tip, indication
      of spindle formation, nucleolar movement into the NP and suggestion of
      chromosomal movement as well); positive tubulin immunostaining of centrosome
      centriole in NPs and also of the underlying region of the nuclear pole,
      indicating the presence of microtubules consistent with mitotic spindle; and
      movement of one X chromosome into NPs, as shown by FISH. CONCLUSION: NPs are
      formed in cells from a variety of tissues, epithelial and nonepithelial. In many
      cases they appear to result from aberrant cell division--namely, unipolar mitosis
      -occurring before prophase events are completed. Another possible mechanism of NP
      formation not involving cell division is through alteration or remodeling of the
      cytoskeleton of the cell; that was shown experimentally to produce nuclear volume
      and shape changes, including formation of protrusions.

PMID- 9568131
TI  - Cytologic and immunoenzymatic findings in CSF from patients with tick-borne
      encephalitis.
AB  - OBJECTIVE: To evaluate the dynamics of cytologic changes in the cerebrospinal
      fluid (CSF) of patients with tick-borne encephalitis (TBE) and to determine the
      various forms of mononuclear cells by immunocytochemical methods. STUDY DESIGN:
      To perform a cytologic analysis of 200 cells in stained sediment of CSF. To
      determine the population and subpopulation of mononuclear cells by using
      monoclonal antibodies. RESULTS: Pleocytosis in CSF in patients with TBE during
      the first three days of illness was, on average, 570 cells per cubic millimeter
      with about 60% neutrophils. Mononuclear cells predominated from the fifth day of
      illness. Among lymphoid cells, 18% carried marker CD20 and 60% of them marker
      CD3. Among monocytoid cells, 66% carried marker CD32. CONCLUSION: CSF cytology
      findings reflect the immunologic and inflammatory changes in the CNS during TBE.

PMID- 9568132
TI  - Nodular pseudoangiomatous stromal hyperplasia of the breast. Cytologic features.
AB  - OBJECTIVE: To define and discuss the cytologic findings in six cases of nodular
      pseudoangiomatous stromal hyperplasia (PASH) of the breast. STUDY DESIGN:
      Retrospective evaluation of the medical records, cytologic and histologic
      material from six patients with palpable mammary PASH. Cases in which PASH was
      associated with other predominant mammary lesions were not included in the study.
      RESULTS: A total of six patients with histologically proven PASH underwent
      aspiration in nine occasions (three patients studied twice). Clinically, five
      patients were diagnosed as having fibroadenoma or another benign lesion, and in
      one patient carcinoma was suspected. In two patients, mammography disclosed rapid
      growth of the lesion. Seven aspirations, performed on five patients, were
      diagnosed as fibroadenoma (n = 5) or fibroadenomatous lesion (n = 2). An eighth
      aspiration was cystic and reported as fibrocystic disease. The last case was
      erroneously diagnosed as suspicious for carcinoma. Even after revision, the
      cytologic similarities of PASH with fibroadenoma were remarkable. Most smears
      were less cellular than those of conventional fibroadenomas. Epithelial clusters
      showed variable size, with a predominance of medium to small groups. Stromal
      elements were minimal or absent. Background cellularity was composed of round to
      oval naked nuclei and others with spindle shapes. Occasional epithelial clusters
      showed cellular dissociation and slight atypia. CONCLUSION: Due to the absence of
      specific cytologic features and similarities to fibroadenoma, a precise diagnosis
      of PASH cannot be made on cytologic material. However, the majority of cases can
      be diagnosed correctly as benign, allowing appropiate treatment.

PMID- 9568133
TI  - Cytologic application of p53 overexpression using immunocytochemistry and
      confocal laser scanning microscopy.
AB  - OBJECTIVE: p53 Protein plays an important role in cellular growth control. This
      study investigated p53 protein expression in cell smears of endometrial
      carcinomas supplemented by confocal laser scanning microscopy (CLSM). STUDY
      DESIGN: Imprints from surgical specimens of 20 endometrial carcinomas were used.
      p53 Protein expression was investigated immunocytochemically using the monoclonal
      antibody pAb1801. Using CLSM, three-dimensional morphology was studied. RESULTS:
      Of the 20 cases of endometrial carcinoma, 8 stained positively for p53 protein.
      p53 Showed heterogeneous intranuclear localization, which appeared to be
      associated with chromatin structure. CONCLUSION: Immunocytochemical detection of
      p53 overexpression in cell samples is practical, and CLSM has vast potentials in
      studying the intranuclear arrangement of chromatin.

PMID- 9568134
TI  - Intraoperative diagnosis of nervous system lesions.
AB  - OBJECTIVE: To determine the accuracy of comparative cytologic and frozen section
      intraoperative diagnosis in neuropathology and the relevance of diagnostic
      accuracy during both craniotomic and stereotactic biopsies and to provide further
      data on rare and/or diagnostically controversial lesions. STUDY DESIGN: Both
      cytologic and frozen section preparations were employed in the intraoperative
      diagnosis of 85 consecutive central and peripheral nervous system lesions
      obtained from classical surgery (70 samples, 4 of which were intramedullary) and
      stereotactic biopsies (15 samples). RESULTS: Combining cytologic and frozen
      section details allowed a fair diagnosis in 81 cases (95.29%), confirmed on
      paraffin sections. In the remaining cases intraoperative misdiagnosis was due to
      technical-staining defects (1 case); absence of tumor differentiation, resolved
      only by ultrastructural examination (2 cases); and marked tumor heterogeneity,
      resolved by wide tissue sampling and immunohistochemistry (1 case). CONCLUSION:
      Besides providing a general description of cytologic and frozen section criteria
      useful in intraoperative diagnostic neuropathology and adding further details
      about some problematic and/or rare entities, our work confirmed: (1) the
      usefulness of comparative cytologic and frozen section examination in the
      intraoperative diagnosis of central nervous system lesions, (2) the relevance of
      the accuracy of intraoperative diagnosis during both craniotomy and stereotaxis,
      including intramedullary samples; and (3) the importance of fair "conduct" in
      intraoperative neuropathology, always comparatively considering morphologic and
      clinicoradiologic data.

PMID- 9568135
TI  - Fine needle aspiration biopsy of recurrent and metastatic osteosarcoma.
AB  - OBJECTIVE: To assess the utility of fine needle aspiration (FNA) biopsy in
      evaluating local recurrence or disseminated metastases in patients with
      osteosarcoma. STUDY DESIGN: Cytology files from Saint Louis University Hospital
      and Indiana University Medical Center were searched for patients with
      osteosarcoma who had undergone FNA biopsy for evaluation of local recurrence or
      disseminated metastases. Clinical information was collected and all aspirate
      smears reviewed. RESULTS: Six FNA biopsies in five patients were procured by
      either the percutaneous or radiologically guided method. All six aspirates were
      diagnostic. Cytologic features showed a discohesive, cellular neoplasm with
      intermediate to large cells and oval to spindle nuclei. Chromatin was coarsely
      granular, with single or multiple nucleoli. Aspirate material included
      multinucleated giant cells and a variable amount of "osteoidlike" extracellular
      matrix. CONCLUSION: FNA biopsy is accurate, and these results reflect its ability
      to diagnose osteosarcoma when there is local recurrence or widely disseminated
      metastases.

PMID- 9568136
TI  - Role of cytopathology in the diagnosis of ocular malignancies.
AB  - OBJECTIVE: To determine the positive predictive value of ocular cytologic
      specimens and to describe the cytopathologic findings encountered in ocular
      samples from patients with intraocular neoplasms. STUDY DESIGN: Intraocular
      fluids and ocular fine needle aspirates (FNAs) cytologically diagnosed as either
      suspicious or positive for malignancy during a 15-year period were reviewed, and
      follow-up was obtained. RESULTS: Seventeen patients with intraocular samples
      diagnosed as suspicious or positive for malignancy (9 vitreous, 6 anterior
      chamber, 3 FNAs) were identified. The mean patient age was 58 years (range, 3
      91). Cytologic diagnoses included: lymphoma (5), suspicious for lymphoma (2),
      melanoma (6), suspicious for melanoma (2), carcinoma (2) and retinoblastoma (1).
      Clinical and/or surgical follow-up was available in 12 cases and was consistent
      with the presence of malignancy in all but one case, which proved to be fungal
      endophthalmitis. One of two patients with a cytologic diagnosis of carcinoma had
      melanoma on follow-up. Cytologic samples suspicious or positive for lymphoma
      showed single, large cells with scant cytoplasm and prominent nucleoli. Cytologic
      samples suspicious or positive for the epithelioid type of melanoma showed
      loosely cohesive groups or single cells, marked cellular pleomorphism, large
      nucleoli, scant to moderately abundant cytoplasm and variable amounts of melanin.
      Cytologic samples from spindle cell melanomas showed spindle cells without
      nuclear or cellular pleomorphism, without hyperchromasia, and with inconspicuous
      nucleoli and occasional nuclear grooves. Loose aggregates of small cells with
      hyperchromatic nuclei and scant cytoplasm characterized the retinoblastoma
      samples. CONCLUSION: The positive predictive value of intraocular fluid cytology
      was 92%. Reactive lymphoid processes may be difficult to differentiate from
      lymphoma and epithelioid melanoma from carcinoma in intraocular cytologic
      specimens.

PMID- 9568137
TI  - Fine needle aspiration diagnosis of a pulmonary metastasis from a cutaneous
      adenoid cystic carcinoma. A case report.
AB  - BACKGROUND: Primary cutaneous adenoid cystic carcinomas (CACC) rarely metastasize
      to the lung. The few documented cases have been diagnosed by surgical biopsy.
      CASE: An 82-year-old female presented with an enlarging lung mass 15 years after
      being diagnosed with CACC. The diagnosis of metastatic adenoid cystic carcinoma
      was made following a computed tomography-guided fine needle aspiration (FNA)
      biopsy. CONCLUSION: Metastatic CACC in the lung can be diagnosed by FNA.
      Knowledge of the patient's clinical history and morphologic variants of CACC is
      important in making the diagnosis.

PMID- 9568138
TI  - AIDS-related primary lymphoma of the pleural cavity. A case report.
AB  - BACKGROUND: Pleural effusions are common in patients with the acquired
      immunodeficiency syndrome (AIDS). Their most frequent causes are Kaposi's sarcoma
      and mycobacterial infections. We report cytologic, immunophenotypic and molecular
      features of a primary pleural non-Hodgkin's lymphoma (NHL) that represent an
      uncommon cause of isolated pleural effusion in patients with AIDS. CASE: A 66
      year-old, human immunodeficiency virus-positive male presented with chest pain
      and dyspnea. He had no history of opportunistic infections or Kaposi's sarcoma. A
      chest radiography displayed a right-sided pleural effusion. Cytology of pleural
      fluid revealed lymphomatous cells with markedly irregular nuclei. Their
      immunophenotype was indeterminate. Computed tomography of the thorax and abdomen
      did not show any tumor mass. Molecular analysis demonstrated that the
      lymphomatous cells had a B-cell genotype and contained Kaposi's sarcoma
      associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) DNA sequences.
      CONCLUSION: This case belongs to a new subgroup of AIDS-related NHL that is
      characterized by unusual morphology, null immunophenotype, B-cell genotype and
      association with both KSHV and EBV.

PMID- 9568139
TI  - Cytodiagnosis of a primary effusion lymphoma. A case report.
AB  - BACKGROUND: Primary effusion lymphoma (PEL), commonly described in AIDS patients,
      is a unique subset of lymphoma in which the neoplastic lymphocytes proliferate
      exclusively in serous cavities. CASE: A 27-year-old male, HIV positive for five
      years and with multiple opportunistic infections in the past, was admitted for
      sudden-onset shortness of breath caused by a pleural effusion. Cytologic
      examination of the pleural fluid revealed medium to large atypical lymphocytes
      with a high mitosis rate, suspicious for lymphoma. Further diagnostic tests, such
      as immunophenotypic analysis and cytogenetic and molecular studies, confirmed the
      diagnosis of PEL. CONCLUSION: Cytopathologists and cytotechnologists should be
      aware of this new entity since additional studies are required for a definitive
      diagnosis.

PMID- 9568140
TI  - Pulmonary alveolar proteinosis. A report of two cases with diagnostic features in
      bronchoalveolar lavage specimens.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare condition that has
      been associated with myriad diseases and disorders. Alveolar spaces are
      progressively filled with a phospholipoproteinaceous material, presumably related
      to a derangement of surfactant production and/or catabolism. The cytologic
      features of PAP in bronchoalveolar lavage (BAL) sediments are unique, and
      recognition of these characteristics can help guide clinical intervention. CASES:
      A 47-year-old male with a history of progressive dyspnea and recent pneumonia
      presented with a five-lobe alveolar infiltrate and subsequently underwent
      bronchoscopic examination. A 31-year-old female with chronic myelogenous leukemia
      in blast transformation developed unresponsive pulmonary infiltrates
      necessitating bronchoscopy with lavage. Both BAL lavage fluid sediments contained
      a homogeneous, basophilic, granular material typical of PAP. The material was
      composed of extracellular, multilamellated bodies when viewed by electron
      microscopy. Both patients required repeated therapeutic whole lung lavage, and
      one died of the disease eight months after the diagnosis. CONCLUSION: Clinical
      presentation, grossly milky BAL fluid and fluid sediment with light microscopic
      findings of basophilic, periodic acid-Schiff-positive, granular debris with
      cholesterol crystals and a few alveolar macrophages suggest this process. The
      light microscopic findings can be confirmed by ultramicroscopic demonstration of
      extracellular multilamellated bodies. BAL with appropriate examination of the
      effluent sediment facilitates the diagnosis of PAP.

PMID- 9568141
TI  - Lymphoepithelial cyst of the pancreas. Report of a case diagnosed by fine needle
      aspiration biopsy.
AB  - BACKGROUND: Lymphoepithelial cysts of the pancreas are very rare lesions. To the
      best of our knowledge, 24 cases are reported in the literature. CASE: A 64-year
      old male presented with gastrointestinal complaints. A computed tomography scan
      of the abdomen disclosed a 55 x 30-mm, homogeneous mass anterior to and
      contiguous with the pancreas. Fine needle aspiration biopsy (FNAB) showed threads
      of tissue composed of stratified squamous epithelium with subepithelial
      lymphocytic infiltrate and keratinous material. CONCLUSION: This case illustrates
      that FNAB is a rapid and reliable technique that can be used as the first
      diagnostic step in cases of cystic lesions of the pancreas. To our knowledge,
      this is the third case reported of this entity diagnosed with FNAB.

PMID- 9568142
TI  - Fine needle aspiration cytology of mixed tall and columnar cell papillary
      carcinoma of the thyroid. A case report.
AB  - BACKGROUND: We report the first case of a composite tumor (tall cell and columnar
      cell variants) of papillary thyroid carcinoma (PTC) diagnosed by fine needle
      aspiration. It is important to differentiate these uncommon aggressive variants
      from the usual indolent papillary carcinomas. CASE: Fine needle aspiration
      cytology was obtained from a rare composite tumor of tall cell and columnar cell
      variants of papillary thyroid carcinoma. The smears showed a cellular aspirate
      with scattered single tumor cells and several tissue fragments arranged in a
      papillary pattern. The tumor cells had abundant nuclear grooves and intranuclear
      pseudoinclusions. Several of the fragments showed columnar cells with nuclear
      pseudostratification, and a few clusters displayed tall columnar cells with basal
      nuclei and abundant cytoplasm. A rare cluster exhibited composite features of
      tall cell and columnar cell variants. CONCLUSION: Columnar cell and tall cell
      variants of PTC manifest aggressive clinical behavior. The differential diagnosis
      of columnar cell variant includes medullary carcinoma of thyroid and metastatic
      adenocarcinoma. Immunohistochemical stains for calcitonin and thyroglobulin play
      an important role in difficult cases. The tall cell variant needs to be
      differentiated from Hurthle cell papillary neoplasm of thyroid, which displays
      prominent nucleoli and lacks the characteristic nuclear features of PTC. The
      preoperative diagnosis of these aggressive variants' is important in planning the
      most appropriate type of treatment.

PMID- 9568143
TI  - Fine needle aspiration cytology of malignant phyllodes tumor with liposarcomatous
      stroma of the breast. A case report.
AB  - BACKGROUND: Liposarcoma arising within a phyllodes tumor is extremely rare. To
      the best of our knowledge, a malignant phyllodes tumor with liposarcomatous
      stroma diagnosed by fine needle aspiration (FNA) has not been reported before.
      CASE: A 39-year-old female had a malignant phyllodes tumor with liposarcomatous
      stroma diagnosed by FNA cytology. Two subtypes of liposarcomatous stroma,
      including lipomalike differentiated and myxoid, were found in the aspirates. The
      cytologic findings were very representative of the histologic features.
      CONCLUSION: It is very important to recognize the cytologic features of such rare
      tumors. An accurate diagnosis preoperatively by FNA permits better therapy
      planning.

PMID- 9568144
TI  - Fine needle aspiration cytology of primary isolated splenic Blastomyces
      dermatitidis. A case report.
AB  - BACKGROUND: Blastomyces dermatitidis is a dimorphic fungus; its usual port of
      entry is the lung. Although any organ system can be secondarily involved, non
      pulmonary sites of primary infection have been reported. CASE: This is the first
      reported case of primary isolated splenic B dermatitidis. The diagnostic value of
      fine needle aspiration cytology was examined by comparing it with the only
      previously reported case of primary (not isolated) splenic B dermatitidis.
      CONCLUSION: In patients with splenic involvement by B dermatitidis, cytologic
      evaluation can be prompt and diagnostic. FNA biopsy in patients with splenomegaly
      is safe and well tolerated.

PMID- 9568145
TI  - Cytodiagnosis of vaginal endodermal sinus tumor. A case report.
AB  - BACKGROUND: Endodermal sinus tumor (EST) of vaginal origin is extremely rare, and
      few previously published reports have described the cytology of this tumor. CASE:
      A high serum alpha-fetoprotein (AFP) level and magnetic resonance imaging
      findings in a 10-year-old female suggested EST of the lower genital tract.
      Laparotomy revealed EST occupying the pelvic cavity. The patient died on the 17th
      postoperative day due to complications from disseminated intravascular
      coagulation. Autopsy was performed immediately after death. The tumor originated
      in the posterior vaginal wall directly below the ectocervical area. Both ovaries
      were involved, and the tumor proliferated to occupy the cavity of the pelvis
      minor. A vaginal smear, obtained on two occasions, revealed severe necrosis with
      few cells, and a diagnosis could not be made. An imprint smear of the tumor
      obtained during surgery showed relatively characteristic cytologic findings of
      EST. Immunocytochemical and immunohistochemical studies revealed staining
      positive for AFP. CONCLUSION: Vaginal EST usually occurs in patients under 3
      years of age. This 10-year-old patient was the oldest among the reported cases.
      Vaginal EST is clinically similar to sarcoma botryoides and clear cell carcinoma,
      and a differential diagnosis is necessary. Immunocytostaining for AFP is
      essential for a definitive cytologic diagnosis of EST.

PMID- 9568146
TI  - Imprint cytology of chondroblastoma of bone. A case report.
AB  - BACKGROUND: Chondroblastoma is a rare benign tumor, and reports on its cytologic
      features are scant. To clarify its cytologic appearance, we report a case along
      with immunohistochemical and electron microscopic findings. CASE: A 23-year-old
      male presented with a pain in his left knee, and a plain roentgenogram revealed
      an osteolytic lesion in the distal epiphysis of the femur. Curettage of the tumor
      was performed with clinical diagnosis of giant cell tumor of bone. Imprint smears
      showed sheetlike clusters of mononuclear tumor cells with scattered,
      osteoclastlike giant cells. Chondroid matrix was focally observed among the cell
      clusters. The histologic appearance was a conventional one, with focal chondroid
      matrix formation. Immunohistochemically, mononuclear tumor cells were diffusely
      positive for S-100 protein. CONCLUSION: Cytologic features of condroblastoma are
      sheetlike clusters of mononuclear cells, scattered osteoclastlike giant cells and
      focal chondroid matrix formation. Immunohistochemical demonstration of S-100
      protein in mononuclear cells helps to make a correct diagnosis.

PMID- 9568147
TI  - Papillary urothelial carcinoma of the urinary bladder demonstrating prominent
      signet-ring cells in a smear. A case report.
AB  - BACKGROUND: The appearance of numerous signetring cells (SRCs) without any other
      type of adenocarcinoma cells originating in papillary transitional cell carcinoma
      (TCC) in a urine smear is rare. CASE: The cytology from mucus-urine that was
      initially obtained by washing from a 69-year-old female revealed three different
      types of cells: (1) numerous single SRC carcinoma-type cells, (2) low grade TCC
      type cells arranged in sheets, and (3) intermediate (transitional)-type cells
      with both aspects of TCC and adenocarcinoma (SRC carcinoma) and mucus in the
      background. The latter two cell populations were retrospectively confirmed after
      histologic diagnosis of a primary papillary TCC with glandular differentiation.
      CONCLUSION: One should keep in mind that even a low grade papillary TCC with
      glandular differentiation of the bladder can exhibit excessive SRC-type cells in
      urine.

PMID- 9568148
TI  - Fine needle aspiration cytology of glycogen-rich clear cell carcinoma of the
      breast. A case report.
AB  - BACKGROUND: Glycogen-rich clear cell carcinoma (GRCC) is a rare variant of breast
      carcinoma that was first described by Hull et al in 1981. The histologic findings
      have been described; however, the cytologic characteristics have not been well
      described. CASE: A 44-year-old female exhibited a palpable mass in her right
      breast. The fine needle aspirate contained cell clusters in a necrotic
      background. In addition to carcinoma cells with increased degrees of nuclear
      atypia, carcinoma cells with less atypia were identified. The tumor cells
      contained small round or ovoid nuclei and abundant, clear cytoplasm. The tumor,
      resected by modified radical mastectomy, was diagnosed as GRCC with detection of
      glycogen accumulation in the cytoplasm. CONCLUSION: Although rare, glycogen-rich
      clear cell carcinoma should be considered in the differential diagnosis of breast
      cancer in fine needle aspiration cytology to prevent misdiagnosis because of its
      varied morphologic patterns and less atypical cytologic features.

PMID- 9568149
TI  - Imprint cytology of Gaucher's disease presenting as a splenic mass. A case report
      with molecular approaches.
AB  - BACKGROUND: Gaucher's disease is an autosomally transmitted lysosomal storage
      disease caused by a defect in the lysosomal enzyme, beta-glucosidase. CASE: A 43
      year-old male presented with splenomegaly and anemia. Magnetic resonance imaging
      examination of the abdomen revealed huge, round masses in the spleen.
      Intraoperative cytology of the spleen showed Gaucher cells that resembled
      macrophages, with eccentric, small, oval nuclei, but distinguished by their
      abundant cytoplasm with the characteristic "wrinkled tissue paper" appearance.
      The cytologic features of the smears correlated well with the histologic sections
      from the splenectomized specimen. The DNA from this patient was examined for
      seven glucocerebrosidase mutations that are known to cause Gaucher's disease. The
      patient was heterozygous for the 754 mutation. Diagnosis was confirmed by a
      deficiency of beta-glucosidase. The residual activity was 15% of control values.
      CONCLUSION: Diagnosis of Gaucher's disease was made cytologically and
      subsequently confirmed by the polymerase chain reaction. Imprint cytology is a
      sensitive diagnostic test, and the combined use of histology and molecular
      techniques offers the highest probability of identifying this common lysosomal
      storage disorder.

PMID- 9568150
TI  - Nuclear pseudoinclusions in angiomyolipoma of the kidney. A case report.
AB  - BACKGROUND: Fine needle biopsy has been utilized for the preoperative diagnosis
      of angiomyolipoma of the kidney. However, the spectrum of diverse nuclear
      morphology shown by the constituent smooth muscle cells of angiomyolipoma has not
      been fully elucidated. CASES: An angiomyolipoma was found incidentally in the
      left kidney of an asymptomatic, 57-year-old woman, and nephrectomy was performed.
      The tumor was composed predominantly of smooth muscle cells occasionally showing
      atypical nuclear features. Small aggregates of adipocytes were also found. Direct
      stamp specimens of the tumor revealed plump, spindle-shaped smooth muscle cells,
      and the nuclei of many of these cells contained large pseudoinclusions
      (cytoplasmic invaginations). Histologic review of an additional four cases of
      renal angiomyolipoma further revealed the frequent occurrence of nuclear
      pseudoinclusions in smooth muscle cells of the tumor. CONCLUSION: Nuclear
      pseudoinclusions on fine needle aspiration cytology of renal angiomyolipoma have
      not received adequate attention. We showed that this finding is a rather common
      nuclear feature in angiomyolipoma. It is presumably one of the manifestations of
      nuclear pleomorphism frequently seen in smooth muscle cells of angiomyolipoma and
      should not be considered an indication of malignancy.

PMID- 9568151
TI  - Scapulohumeral tuberculosis diagnosed by fine needle aspiration cytology.

PMID- 9568152
TI  - Fine needle aspiration of breast hamartoma.

PMID- 9568153
TI  - Effective communication about breast aspiration.

PMID- 9568154
TI  - Hepatoblastomas and undifferentiated (embryonal) sarcoma of the liver: updating
      references while revising galley proofs.

PMID- 9568155
TI  - Uniform approach to breast fine needle aspiration biopsy.

PMID- 9568156
TI  - Imprint cytology of malignant plasmacytoid myoepithelioma of the palate.

PMID- 9568157
TI  - Peripheral giant cell granuloma: a diagnostic pitfall in FNAC material.

PMID- 9568158
TI  - Expression of dipeptidyl aminopeptidase IV in human thyroid tissues.

PMID- 9568159
TI  - Metastatic medullary thyroid carcinoma in a breast fine needle aspirate:
      cytopathologic findings.

PMID- 9568160
TI  - Primary hepatic undifferentiated embryonal sarcoma: cytopathologic findings in
      peritoneal washings.

PMID- 9568161
TI  - Follicular carcinoma of thyroid gland presenting as scalp metastasis.

PMID- 9568162
TI  - Breast filariasis mimicking Paget's disease.

PMID- 9568163
TI  - Microfilariae in fine needle aspirates of the liver.

PMID- 9568164
TI  - XIIIth International Congress of Cytology. Tokyo, Japan, May 10-14, 1998.
      Abstracts.

PMID- 9568165
TI  - Glucosylceramide: a marker for multiple-drug resistant cancers.
AB  - BACKGROUND: Multiple-drug resistance (MDR) is a major reason for chemotherapy
      failure. Herein we describe glucosylceramide, a new marker for MDR. METHODS:
      Cellular lipids were analyzed in three human MDR cancer cell lines and their drug
      sensitive counterparts. Analysis of glucosylceramide was also performed in six
      melanoma specimens and one breast tumor specimen obtained from patients who had
      undergone chemotherapy. Glucosylceramide, analyzed by mass and by cellular
      utilization of radiolabeled precursor ([3Hpalmitic acid), was isolated by lipid
      extraction techniques and resolved from other components by thin-layer
      chromatography. RESULTS: Glucosylceramide was present consistently in all MDR
      cell lines and was absent, or present only at very low levels, in the
      corresponding drug-sensitive cells. Examination of human tumor specimens
      documented presence of the marker in all patients who had failed chemotherapy,
      and absence of the marker in each of the patients with known clinical response to
      chemotherapy. The response to chemotherapy was followed for a median of 8 months
      in melanoma patients and for 22 months in the breast cancer patient. CONCLUSION:
      These findings suggest that glucosylceramide may hold clinical significance for
      the early identification of drug-resistant tumors.

PMID- 9568166
TI  - Mobilization of peripheral blood stem cells in patients with advanced thoracic
      malignancies after irinotecan (CPT-11) administration.
AB  - We evaluated the mobilization of peripheral blood stem cells (PBSCs) after the
      administration of chemotherapy including irinotecan (CPT-11) in individuals with
      advanced thoracic malignancies including lung cancer and mesothelioma. All
      patients were previously untreated. The numbers of CD34+ cells, CD34+ 38- cells,
      and colony-forming units granulocyte-macrophage (CFU-GM) in peripheral blood were
      determined to monitor PBSCs at least twice a week. Granulocyte colony-stimulating
      factor (G-CSF) (75 micrograms/body per day) was administered at the onset of
      neutropenia [absolute neutrophil count (ANC) of < 1000/microliter] until the ANC
      exceeded 5000/microliter. In patients who received G-CSF, sufficient counts of
      the PBSCs for PBSC transplantation were mobilized at the time when the white
      blood cell count was > 5000/microliter. CPT-11 with G-CSF is thus a promising
      induction regimen for PBSC transplantation. Patients who did not develop
      neutropenia after chemotherapy showed a significantly (p = 0.005) higher number
      of CD34+ cells in the peripheral blood at steady state (median, 1818; range, 1534
      to 4433; n = 8) than those who developed neutropenia (median, 666; range, 608 to
      1553; n = 5). This parameter may thus prove a useful marker for predicting
      neutropenia after the administration of CPT-11.

PMID- 9568168
TI  - Radiochemosensitivity and expression of p53 in patients with esophageal cancer
      treated by absolute noncurative resection.
AB  - The aim of this study was to investigate the relationship between the expression
      of p53 protein and radiochemosensitivity in patients with advanced esophageal
      cancer. We analyzed the expression of p53 protein by an immunohistochemical
      method in tumors from 28 patients with advanced esophageal cancer who had been
      treated by absolute noncurative resection. Four patients died from postoperative
      complications. Fourteen of the remaining 24 patients were treated with
      postoperative radiochemotherapy. The expression of p53 protein was detected in
      tumors from 16 of 28 patients (57.1%). The mean survival period was 16.4 months
      for 14 patients treated with radiochemotherapy, as compared to 6.9 months for 10
      patients who were not treated with radiation therapy (P = 0.112). In the case of
      the 14 patients treated with radiochemotherapy, the mean survival period was 24.7
      months for seven patients with p53-negative tumors while it was only 8 months for
      seven patients with p53-positive tumors. However, difference was not
      statistically significant (P = 0.149). Postoperative radiochemotherapy prolonged
      the survival of some patients with noncuratively operated esophageal tumors that
      were p53-negative. However, the enhanced survival was not statistically
      significant.

PMID- 9568167
TI  - Shortened time to recovery from chemotherapy induced neutropenia in pediatric
      patients with high dose combined cytokines.
AB  - Granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony
      stimulating factor (GM-CSF) are cytokines which have been extensively
      administered as monotherapy to patients with a variety of hematopoietic disorders
      at dosages of 5 mcg/kg/day. Because their spectrum of activity is both singular
      and simultaneously overlapping, we postulated that combined therapy would be more
      advantageous than monotherapy. Since 1992 we have carried out a study of G-CSF
      and GM-CSF as monotherapy or in combination in pediatric patients with solid
      tumors following chemotherapy induced nadirs of 0-800 WBC/mm3. When combined, the
      cytokines were given twice per day at 2.5 or 5.0 mcg/kg. For the monotherapy
      groups, either cytokine at 5 mcg/kg or 10 mcg/kg was given once daily. The mean
      time to recovery from neutropenia nadir ranged from 6.6-8.2 days in patients
      receiving a total of 10 mcg/kg/day compared to 10.4-10.6 days in patients treated
      with 5 mcg/kg/day. Side effects were ephemeral eosinophilia. The dosage of 10
      mcg/kg/day appears to be a better dosage for pediatric patients with a slight
      advantage in the combined twice a day schedule (6.6 days).

PMID- 9568169
TI  - Patients' opinion and use of non-proven therapies related to their view on cancer
      aetiology.
AB  - BACKGROUND: The aim of the study was to investigate patients' attitudes to and
      use of nonproven therapies (NPTs) in view of their opinions about causes of
      cancer. MATERIAL AND METHODS: A comparative questionnaire-based study was given
      to patients with non-malignant disease (n = 305) seen in general practice and
      cancer patients (n = 252) seen at the Department of Oncology, University Hospital
      of Tromso. RESULTS: Among non-cancer patients significantly more NPT-positive
      than NPT-negative patients considered the environment to be an important cancer
      cause (74% versus 52%) and that food and drink may be carcinogenic (57% versus
      40%). For cancer patients, there was no such difference. 60% of non-cancer
      patients and 35% of cancer patients believed that life style changes could alter
      the natural course of cancer. In both groups of patients, the NPT-positive
      believed, to a higher degree than the NPT-negative, that the outcome of cancer
      could be improved by a change in life style (69% and 48% versus 53% and 29%).
      CONCLUSION: Patients positive to NPTs have firmer beliefs with respect to the
      importance of environmental factors than non-believers/-users. Moreover, these
      patients believed more strongly than NPT-negative patients that change of
      lifestyle may influence the outcome of cancer positively.

PMID- 9568170
TI  - [111In-DTPA-D-Phe1]-octreotide scintigraphy in patients with hormone-refractory
      prostatic adenocarcinoma can predict therapy outcome with octreotide treatment: a
      pilot study.
AB  - A pilot study to evaluate the predictive value of Indium-111-labelled
      somatostatin analogue [DTPA-D-Phe1]-octreotide scintigraphy (OctreoScan111) in
      the Octreotide treatment of hormone-refractory prostatic adenocarcinoma was
      initiated. Ten patients were investigated with OctreoScan111 with regard to
      disease extension and tumor-to-background ratio. Subsequently, the patients were
      treated with Octreotide (Sandoz, Basel, Schweiz) at a dose of 100 micrograms
      twice a day subcutaneously. Three patients experienced symptomatic relief, and
      two of these responded with a decrease in PSA. Three patients did not notice any
      difference after 6 months of treatment and two of them developed an increase in
      their PSA value. One patient progressed after five months as regards both PSA and
      symptoms. Three patients were not able to complete treatment. Of the seven
      evaluable patients, the three with the highest tumour-to-background ratios at
      OctreoScan111 were those patients with reduced or stable PSA levels, and none of
      these progressed during treatment. Previous reports along with this study
      demonstrate that only a minority of patients with hormone-refractory prostatic
      adenocarcinoma benefit from Octreotide treatment. However, OctreoScan111
      investigations may identify patients who will respond to Octreotide therapy.

PMID- 9568171
TI  - Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in
      advanced colorectal cancer.
AB  - BACKGROUND: Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients
      (pts) with advanced colorectal cancer has been demonstrated to produce a highly
      significant benefit over single-agent 5-FU in terms of tumor response rate, but
      this advantage does not translate into an evident improvement of overall
      survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase
      II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken.
      PATIENTS AND METHODS: Seventy advanced colorectal patients were enrolled and
      treated by a weekly outpatient combination regimen according to the following
      schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm
      over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4
      hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were
      pretreated with fluoropyrimidines. RESULTS: The overall objective response rate
      (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated
      pts, and 6 PR (23% OR) were reported among previously treated pts. Major side
      effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot
      syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however,
      this did not significantly influence the therapeutic programme. Median 5-FU dose
      intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and
      pretreated pts, respectively. CONCLUSIONS: L-Leucovorin modulation of weekly
      short-term continuous infusion of high-dose 5-fluorouracil appeared a well
      tolerated outpatient regimen; it demonstrated a high activity in advanced
      colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based
      chemotherapy.

PMID- 9568172
TI  - Neoadjuvant chemotherapy of gastric cancer with oral UFT (a mixture of uracil and
      fturafur) during the waiting period for surgery.
AB  - Our previous experience has demonstrated that growth of gastric cancer during the
      waiting period for surgery cannot be neglected, and some patients hope to receive
      prophylactic treatment to inhibit the growth of tumor until surgery. The present
      study was designed to assess the clinical benefits of preoperative chemotherapy
      with oral UFT for gastric cancer during the waiting period for surgery. Fifty
      patients with gastric cancer (24 early, 25 advanced and 1 recurrent cancers) were
      treated with oral UFT at 300-600 mg/day for 7-36 days before surgery and the
      objective responses and the postsurgical survivals were evaluated. In 42 of 50
      patients objective responses of primary lesions were assessed by endoscopy or
      upper gastrointestinal series examination, and 2 CRs, 15 PRs and 25 NCs were seen
      (40% response). The histological effect was evaluated in 50 patients and the
      following classifications were made: grade 3 (complete disappearance or necrosis
      of tumor cells), 2; grade 2 (necrotic changes > 2/3 area), 4; grade 1b (> 1/3
      area), 7; grade 1a (< 1/3 area), 15; and grade 0 (no histological changes), 22. A
      longer period of UFT administration was associated with CR or PR. All the
      patients underwent gastrectomy (38 curative and 12 palliative gastrectomies): all
      patients with Stage I-III primary gastric cancer are alive after surgery, and the
      50% survival period of the patients with Stage IV cancer was 20 months. The side
      effects were not serious, including slight myelotoxicity, liver dysfunction and
      anorexia. It is concluded that preoperative chemotherapy for gastric cancer with
      oral UFT on outpatient basis may result in down-staging as well as the prevention
      of tumor growth during the waiting period for surgery without serious side
      effects.

PMID- 9568173
TI  - Immunoreactivity of nm23-H1 protein in renal cell carcinoma.
AB  - Formalin-fixed, paraffin-embedded tissue blocks from 25 surgical specimens of
      renal cell carcinoma (RCC) including 13 adjacent normal renal tissues were
      investigated. The specimens were examined by immunohistochemistry using the
      monoclonal antibody, nm23-H1. The positive immunostaining of nm23-H1 protein was
      confined primarily to the cytoplasm of both normal renal tubular epithelial cells
      and renal tumor cells. Immunostaining of nm23-H1 protein was reduced
      significantly in RCC as compared to the normal renal tissues (P = 0.003). The
      positive immunostaining of nm23-H1 protein was seen in 92% (12/13) of normal
      renal tissues and in 60% (15/25) of RCC. No relationship was found between
      immunostaining of nm23-H1 protein and the patient's clinicopathological factors
      including age, tumor size, tumor location, tumor grade and tumor stage.
      Furthermore, immunostaining of nm23-H1 protein was not correlated with patient
      survival. Although immunoreactivity of nm23-H1 protein in patients with RCC was
      not correlated with survival, nm23-H1 protein may play a role in human renal
      tubular tumorigenesis.

PMID- 9568174
TI  - The serum assay of soluble CD44 standard (sCD44-st), CD44 splice variant 5 (sCD44
      v5), and CD44 splice variant 6 (sCD44-v6) in patients with cervical cancer.
AB  - The pretreatment serum levels of soluble CD44 standard (sCD44st), CD44 splice
      variant 5 (sCD44-v5), and CD44 splice variant 6 (sCD44-v6) were retrospectively
      measured in 37 patients with untreated cervical cancer and in 36 patients with
      benign gynecological diseases as controls. Median sCD44-st levels were
      significantly higher in patients with cervical cancer than in controls (547
      ng/ml, range 244-880 ng/ml versus 400.5 ng/ml, range 217-723 ng/ml, p = 0.004),
      whereas sCD44-v5 and sCD44-v6 concentrations were significantly lower in the
      former (34 ng/ml, range 0-140 ng/ml versus 44 ng/ml, range 11-109 ng/ml, p =
      0.038; and 37 ng/ml, range 1-191 ng/ml versus 52.5 ng/ml, range 11-173 ng/ml, p =
      0.007, respectively). sCD44-st, sCD44-v5, and sCD44-v6 levels were not related to
      FIGO stage and histologic type. Moreover, among patients with stage Ib-IIa
      cervical cancer, the preoperative levels of these glycoproteins correlated with
      neither the common prognostic variables nor the clinical outcome. Therefore, the
      serum assay of sCD44-st, sCD44-v5, and sCD44-v6 seems to have no clinical
      relevance for the management of patients with cervical cancer.

PMID- 9568175
TI  - Significance of nm23 mRNA expression in human hepatocellular carcinoma.
AB  - It has been proposed that nm23-H1, a candidate suppressor gene for metastasis,
      plays an important role in the metastasis of human tumors. In order to
      investigate its role in the human hepatocellular carcinoma (HCC), 18 matched
      pairs of tumorous and adjacent nontumorous liver tissues of hepatectomy from
      patients with HCC were studied by quantitative reverse transcription-PCR. Further
      analyses of the nm23-H1 gene were also done. The results of these molecular
      studies were correlated with the clinicopathologic features of the patients. Nm23
      H1 transcript was expressed in all neoplastic and adjacent nontumorous liver
      tissue. The level of expression, however, did not correlate well with the
      extension or metastatic potential of the tumors. Instead, in 15 (83.3%) of 18
      HCC, nm23-H1 expression was higher in the tumorous tissues, compared with the
      adjacent nontumorous tissues; and significantly higher levels of nm23-H1 mRNA
      expression was detected in HCC with poor differentiation (Edmonson
      classification, III and IV) than those with moderate differentiation (I and II).
      Southern blot analysis of nm23-H1 gene revealed neither amplification nor loss of
      heterozygosity of all HCC tissues examined. Direct sequencing of the nm23-H1 gene
      in all HCC tissues detected no mutations. Our findings suggested that increased
      nm23-H1 mRNA expression is correlated with HCC tumor progression.

PMID- 9568176
TI  - Radiation therapy and chemotherapy in the treatment of head and neck extranodal
      non-Hodgkin's lymphoma in early stage with a high grade of malignancy.
AB  - BACKGROUND: Optimal management of patients with localized head and neck
      extranodal lymphoma remains controversial, both because of the lack of randomized
      studies and because of the heterogenous grouping of most reported series.
      MATERIALS AND METHODS: Patients treated at our institution between 1974 and 1993
      for extranodal head and neck lymphoma were retrospectively analyzed and
      classified. The therapy and outcome of 92 patients classified as having an
      intermediate (42) and high (50) level of malignancy according to the Working
      formulation and in stage I (39) or II (53) of the Ann Arbor Staging System were
      considered. Fifty-three patients (57.6%) received chemotherapy alone, and 39
      (42.4%) combined radiochemotherapy. RESULTS: The different treatment schedules
      allowed these patients to achieve global actuarial 5-year overall, event-free,
      and relapse-free survival rates of 81.2%, 78.1% and 89.3%, respectively. The
      patients that received combined modality treatment reported actuarial 10-year
      event-free and relapse-free survival rates of 65.3% and 90.7%, respectively, with
      a suggestion of decreased treatment-related morbidity compared to patients
      treated with chemotherapy. CONCLUSIONS: Our results underscore the important
      treatment role of combined radiochemotherapy for early stage intermediate and
      high grade lymphomas.

PMID- 9568179
TI  - Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham
      histological grades in a series of 825 cases of breast cancer: major importance
      of the mitotic count as a component of both grading systems.
AB  - The most commonly used system in Europe for breast carcinoma was developed by
      Scarff, Bloom and Richardson (SBR). It was recently modified by Elston and Ellis
      and significant improvement in reproducibility has been shown by using precise
      grading guidelines. This study investigated whether the use of this new grade
      (defined as the Nottingham grade, NG) would improve the prognostic stratification
      of patients. The respective prognostic value of the two grading schemes was
      compared in a retrospective series of 825 patients uniformly treated for a small
      invasive breast carcinoma and followed for a median of 6 years. Univariate and
      multivariate analysis showed that both histological grades were strongly
      correlated to overall and metastasis free survival. We have separately analysed
      the prognostic value of each of the three components used to assess the two
      grading systems and found that the mitotic index was the only significant
      prognostic factor for 5 year survival. Univariate analysis showed the count to be
      more discriminant in the NG scheme (p = 0.0006) than in the SBR scheme (p =
      0.04). However, in univariate and multivariate analysis, the prognostic value of
      the global NG was not significantly better than SBR grade. This may be related,
      in part, to an uneven distribution of cases reflected by a much lower number of
      cases with a high mitotic index in the NG system (2%) than in the SBR system
      (10%). Our study emphasizes the importance of the mitotic count in assessing the
      prognosis of breast cancers and indicates that the factors which condition this
      count (tissue processing, microscopic observation, threshold) must be well
      standardized and controlled.

PMID- 9568177
TI  - Protein expression of p53, p21WAF1, and Rb as prognostic indicators in patients
      with surgically treated hepatocellular carcinoma.
AB  - Many genes participate in the regulation of cell cycle progression from G1 to S
      phase. Functional loss of one or more of these genes has been reported to be
      associated with carcinogenesis and/or tumor progression and poor prognosis in
      many cancers. In a series of 126 patients with hepatocellular carcinoma (HCC), we
      immunohistochemically evaluated tumor expression of the cell cycle-related gene
      protein products of Rb, p21 (WAF1), and p53. Positive immunostaining for Rb, p21,
      and mutant p53 protein was detected in 58%, 33%, and 37% of the tumors,
      respectively. The proportion of HCCs exhibiting aberrant p53 protein expression
      increased significantly with advancing stage of disease (p < 0.001), poorer
      histological classification of differentiation (p < 0.01), and increasing tumor
      size (p < 0.01). A decrease in the proportion of HCCs expressing p21 protein was
      also associated with advancing clinical stage of disease (p < 0.01), and larger
      tumor size (p < 0.05). The only clinicopathological feature found to be
      associated with Rb status, was intrahepatic metastasis, which occurred with a
      higher frequency in HCCs exhibiting positive immunoreactivity for Rb protein
      expression (p < 0.05). Multivariate survival analysis revealed that, amongst the
      protein products of the different genes evaluated, only positive immunostaining
      for aberrant p53 protein expression served as an independent prognostic
      indicator, being significantly associated with worse survival in patients with
      HCC (p = 0.023). Analysis for relationships between gene products showed an
      inverse correlation between expression of aberrant p53 protein and p21 protein (p
      < 0.01), and also an inverse correlation between p21 protein and Rb protein
      expression (p < 0.05) in these cases of HCC. These findings demonstrate that
      positive immunostaining for mutant p53 protein expression is a significant
      indicator of tumor progression and poor prognosis, confirm that p21 protein
      expression is induced in a p53-dependent manner, and suggest that Rb protein
      expression may be regulated to some extent by p21 in HCC.

PMID- 9568178
TI  - Body size as a factor in different ages and breast cancer risk in Taiwan.
AB  - A matched case-control study was done on 175 pathologically proven new cases of
      female breast cancer from National Taiwan University Hospital from February 1993
      to June 1994 and 457 hospital controls individually matched for age and date of
      admission. Height and weight during one year before the first full-term pregnancy
      and one year before admission were collected from a questionnaire interview. Body
      mass index (BMI) (kg/m2) was derived accordingly. Demographic and reproductive
      characteristics, and family history of breast cancer were collected and adjusted
      as potential confounders. Conditional multiple logistic regression analysis was
      used to estimate the effect for each risk factor regarding body size of different
      ages. After adjustment for potential confounders, higher weight and BMI during
      one year before first full-term pregnancy were associated with a moderately lower
      risk of breast cancer especially in the premenopausal group. The heaviest group
      (> or = 65 kg) during one year before admission also had a moderately lower
      breast cancer risk. Height did not show any significant association with breast
      cancer risk. Weight and BMI gain were associated with an elevated breast cancer
      risk in the postmenopausal group but with wide confidence limits. The results of
      this study imply that adipose tissue may interfere with ovarian endocrine in the
      younger age group, and that there is increased hormonal production after obvious
      weight gain.

PMID- 9568180
TI  - pS2 is an independent prognostic factor for post-relapse survival in primary
      breast cancer.
AB  - BACKGROUND: The pS2 protein is involved in the maintenance of the integrity of
      the gastrointestinal tract. In breast cancer pS2 can be demonstrated in at least
      half of the tumors and probably reflects the functional status of ER. Several
      features make it likely that pS2 is involved in growth regulation. PATIENTS AND
      METHODS: We have investigated the value of immunohistochemical pS2 determination
      as a prognostic factor in 339 breast cancer patients with long follow-up from one
      hospital. RESULTS: A prognostic role for pS2 could not be demonstrated
      considering disease-free and overall survival, although in pS2-negative tumors a
      trend for less locoregional relapse was found. However, in multivariate analysis
      pS2 showed independent prognostic value for post-relapse survival. CONCLUSIONS:
      PS2 is an independent prognostic factor for post-relapse survival, most likely
      because it is a predictive factor for response to systemic therapy.

PMID- 9568181
TI  - Correlation of immune cell activities and beta-endorphin release in breast
      carcinoma patients treated with galactose-specific lectin standardized mistletoe
      extract.
AB  - A prospectively randomized clinical study was performed with breast carcinoma
      patients to determine the correlation of defined parameters of the cellular
      immunity and beta-endorphin plasma levels after mistletoe lectin (ML-1)
      standardized therapy. The subcutaneous administration of optimal ML-1 dosages
      (0.5-1.0 ng ML-1/kg body weight; twice a week) induced an increased beta
      endorphin plasma level, enhanced activity of peripheral blood natural killer (NK
      )cells and T-lymphocytes (expression of CD-25/interleukin-2 receptors and HLA/DR
      antigens). Statistical analysis of the data (Spearman correlation) revealed a
      significant correlation between NK- and T-cell activity and beta-endorphin plasma
      level. Thus, an obvious correlation between immune system and the neuroendocrine
      system may be anticipated which might gain therapeutical relevance.

PMID- 9568184
TI  - Epithelial-myoepithelial carcinoma of the salivary glands: a review of
      literature.
AB  - Epithelial-myoepithelial carcinoma (EMC) of the salivary glands is a rare tumor
      first described by Donath et al in 1972 and recognized as a distinct pathologic
      entity in the 1991 WHO classification. The EMC comprises approximately 1% of all
      salivary gland tumors. The histological hallmark is a biphasic cell arrangement
      formed by an inner layer of duct-forming epithelial cells and an outer layer of
      myoepithelial cells. The epithelial-myoepithelial dualism is confirmed using
      immunohistochemical methods: the epithelial cells are immunoreactive for low
      molecular weight keratin; the myoepithelial cells are immunoreactive for S-100
      protein, muscle specific actin and vimentin. Most reported follow-up information
      indicates that EMC is a low-grade malignant tumor; however, from the analysis of
      the various series it is demonstrated that tumors with a solid growing pattern,
      nuclear atypia, DNA aneuploidy and high proliferative activity, generally have a
      more aggressive behavior and a higher frequency of local recurrences and
      metastases.

PMID- 9568183
TI  - Thiamine supplementation to cancer patients: a double edged sword.
AB  - The objectives of this review are to (a) explain the mechanism by which thiamine
      (vitamin B1) promotes nucleic acid ribose synthesis and tumor cell proliferation
      via the nonoxidative transketolase (TK) pathway; (b) estimate the thiamine intake
      of cancer patients and (c) provide background information and to develop
      guidelines for alternative treatments with antithiamine transketolase inhibitors
      in the clinical setting. Clinical and experimental data demonstrate increased
      thiamine utilization of human tumors and its interference with experimental
      chemotherapy. Analysis of RNA ribose indicates that glucose carbons contribute to
      over 90% of ribose synthesis in cultured cervix und pancreatic carcinoma cells
      and that ribose is synthesized primarily through the thiamine dependent TK
      pathway (> 70%). Antithiamine compounds significantly inhibit nucleic acid
      synthesis and tumor cell proliferation in vitro and in vivo in several tumor
      models. The medical literature reveals little information regarding the role of
      the thiamine dependent TK reaction in tumor cell ribose production which is a
      central process in de novo nucleic acid synthesis and the salvage pathways for
      purines. Consequently, current thiamine administration protocols oversupply
      thiamine by 200% to 20,000% of the recommended dietary allowance, because it is
      considered harmless and needed by cancer patients. The thiamine dependent TK
      pathway is the central avenue which supplies ribose phosphate for nucleic acids
      in tumors and excessive thiamine supplementation maybe responsible for failed
      therapeutic attempts to terminate cancer cell proliferation. Limited
      administration of thiamine and concomitant treatment with transketolase
      inhibitors is a more rational approach to treat cancer.

PMID- 9568182
TI  - Prognostic factors influencing complete response to treatment and survival of
      patients with nasopharyngeal cancer.
AB  - The identification of prognostic factors influencing local control and survival
      of patients with nasopharyngeal cancer (NPC) might help in pointing out those
      patients who would probably benefit from primary treatment. A series of 137 Greek
      patients with locally advanced NPC treated with chemotherapy and/or radiation
      were analyzed for significant prognostic factors influencing complete response
      (CR) to treatment, time to progression (TTP) and overall survival (OS). After the
      completion of treatment, 92 (67%) patients achieved CR. Logistic regression
      analysis revealed that only T classification was significant for CR (p = 0.0058).
      After a median follow-up of 5 years, 66 (48%) patients demonstrated tumor
      progression and 64 (47%) died. Median TTP was 25.8 months (range, 0.3-118+) and
      median survival 58.3 months (range, 0.3-124+). Cox proportional hazards model
      identified age (p = 0.024) and T classification (p = 0.009) as significant
      factors for TTP. These two factors were also found to be significant for OS (p =
      0.005 and p = 0.013, respectively). The present study has shown that major
      prognostic factors influencing the outcome of our patients with NPC are similar
      to those reported in recent Chinese studies. These prognostic factors may be used
      as stratification factors in randomized clinical trials.

PMID- 9568186
TI  - Clinical contribution of bcl-2, p53 and Ki-67 proteins in pancreatic ductal
      adenocarcinoma.
AB  - The expression of apoptosis suppressing protein bcl-2, tumour-suppressor protein
      p53, and proliferation marker Ki-67 and their possible prognostic value were
      analysed in pancreatic ductal adenocarcinoma. Fifty-two % (34/64) of the samples
      were positive for bcl-2 and immunostaining were mainly localized in the cytoplasm
      of tumour cells. Bcl-2 expression was not related to tumour grade, DNA ploidy or
      S-phase fraction or to any clinical parameters. In univariate analysis bcl-2
      expression predicted favourable outcome (p = 0.008). Positive nuclear staining
      for p53 was found in 40% (24/59) of samples and 80% (60/74) of the tumours were
      positive for Ki-67. p53 and Ki-67 expressions were not related to patient
      survival. According to our results, bcl-2 expression seems to be a predictor of
      disease outcome and may have some clinical value in human pancreatic cancer.

PMID- 9568198
TI  - A unifying concept of primary venous insufficiency.

PMID- 9568185
TI  - Ras p21 immunostaining in early stage squamous cervical carcinoma: relationship
      with lymph nodal involvement and 72 kDa-metalloproteinase index.
AB  - BACKGROUND: Ras p21 expression seems to be associated with aggressiveness of
      neoplastic growth and metastatic potentially in human solid tumors. In our series
      of early-stage squamous cervical carcinoma, we evaluated ras p21 expression with
      respect to lymph nodal involvement; the aim was to analyse the ras p21
      immunostaining as potential marker of lymphatic spread, and investigate the
      relationship between ras p21 expression and 72 kDa-metalloproteinase
      immunostaining. PATIENTS AND METHODS: 46 patients with FIGO stage I squamous cell
      cervical carcinoma, who had undergone primary radical surgery with systematic
      pelvic and paraaortic lymphadenectomy (Piver's type III) at the Institute of
      Gynecologic and Obstetrics, Ancona University, were recruited from our series of
      59 consecutive cases, and included the study. Any characteristic that could be
      relevant for prognosis was recorded such as: histologic grade of differentiation,
      tumor size, lymphatic spread, or adjuvant radiotherapy. Immunohistochemical
      staining was performed using the avidin-biotin peroxidase complex method (LSAB,
      Dako, Copenhagen, Denmark). Monoclonal antibody anti-pan ras (Ab-1) (Oncogene
      Science) and affinity purified rabbit anti-72 kDa-metalloproteinase antibody were
      used. Positivity for ras p21 was evaluated by semiquantitative analysis, while 72
      kDa-metalloproteinase staining was expressed as the percentage of positive cells
      per 10(3) counted neoplastic cells (index). RESULTS: The expression of ras p21
      was observed in 31 patients (67%) with FIGO stage I squamous cervical carcinoma.
      No connection was found between ras p21 expression and tumor size (P = 0.2), or
      histologic grade (P = 0.9), while a significant relationship was observed with
      respect to lymph nodal status (p = 0.048). By analysing 72 kDa-metalloproteinase
      immunostaining, ras p21 positive carcinomas showed significantly higher 72 kDa
      metalloproteinase index than the negative ones (mean + standard deviation, 23.3%
      + 7.7% and 13.8% + 5.1% respectively, and P < 0.001). CONCLUSIONS: Though the
      relatively small size of our series does not allow any definitive conclusion, a
      significant relationship between ras p21 expression and risk of lymphatic spread
      was detected in early-stage cervical carcinoma. ras p21 positivity seems to be an
      indicator of neoplastic aggressiveness and lymphatic spread, and is associated
      with significantly higher expression of 72 kDa-metalloproteinase.

PMID- 9568187
TI  - Prospective studies of p53 and c-erbB-2 expression in relation to
      clinicopathological parameters of human ductal breast cancer in the second stage
      of clinical advancement.
AB  - BACKGROUND: The association between p53 and c-erbB-2 overexpression relation to
      ER status in ductal breast carcinoma is still unclear. Our aim was investigate
      the prognostic importance of the overexpression of c-erbB-2, p-53 factor, and ER
      status in stage II of human ductal breast cancer. MATERIALS AND METHODS: Th.
      expression of c-erbB-2 and p53 oncoproteins was evaluated by immunoperoxidase
      technique (PAP) in 62 cases of ductal breast carcinoma. The relationship between
      these cell growth regulatory factors was estimated and compared with the presence
      estrogen receptor (ER), tumor grading, tumor size, lymph node involvement, age
      patients and number of relapses up to the second year after surgery. RESULTS: c
      erbB-2 overexpression was found in 44% and p53 in 45% of carcinomas. ER level was
      usually inversely proportional to the presence of studied molecular markers.
      Stratifying patients on the basis of c-erbB-2, p53 and ER status revealed that
      the combination c-erbB-2 and p53 overexpression accompanied by undetectable ER,
      identified the population of poorly differentiated tumors and patients with a
      high incidence of axillary lymph node metastases and shorter relapse time. On the
      other hand, undetectable values of molecular markers were associated with a low
      grade of tumors and a lack of lymph nodes involvement. CONCLUSIONS: Estimation of
      c-erbB-2, p53 and ER status seems to be a powerful tool to discriminate between
      different phenotypes of breast carcinoma. c-erbB-2 and p53 oncoproteins have been
      recognized as independent molecular markers of aggressive tumor behaviour.

PMID- 9568199
TI  - The preoperative duplex examination.
AB  - BACKGROUND: Duplex evaluation of varicose veins has been described since 1986,
      but is still not used as routine examination prior to surgery. OBJECTIVE: To
      illustrate the importance of preoperative duplex varicose vein scan for the
      selection of operation and as a guide to surgery. METHODS: Illustration of
      varicose patterns and anatomical details provided by duplex but difficult or
      impossible to obtain by other means. CONCLUSION: Routine preoperative duplex
      evaluation is mandatory if varicose vein surgery is to be done on patients with
      accurate diagnosis.

PMID- 9568200
TI  - A study of the competency of the saphenopopliteal junction by duplex
      ultrasonography.
AB  - BACKGROUND: Objective determination of saphenopopliteal junction incompetency has
      eluded surgeons for many years. With the advent of duplex ultrasonography
      incompetency of the saphenopopliteal junction can be determined with an
      acceptable degree of clinical certitude. OBJECTIVE: This study was undertaken in
      order to determine the accuracy of duplex ultrasonography in studying the
      competency of the saphenopopliteal junction. METHODS: A total of 50 patients were
      included in the study, and the saphenopopliteal junction was studied bilaterally
      in each patient. The Biosound Phase II Duplex Ultrasound System with a 7.5-mHz B
      mode imaging was used. RESULTS: The degree of accuracy of ascertaining the
      competency of the saphenopopliteal junction was approximately 96%. CONCLUSION:
      This test is reliable, and provides helpful information to the clinician.

PMID- 9568201
TI  - Transillumination mapping prior to ambulatory phlebectomy.
AB  - BACKGROUND: Ambulatory phlebectomy (AP) for removal of varicose and reticular
      veins has become a very popular and widely used in-office outpatient technique
      over the past decade. One of the major obstacles of this or any other surgical
      vein removal technique is the technical difficulty presented to the surgeon by
      the disappearance of the veins to be removed when the patient is positioned
      horizontally on an operative table. Preoperative marking is therefore essential.
      OBJECTIVE: To investigate whether use of transillumination would facilitate and
      enhance marking of varicose veins prior to AP, we performed a study in which both
      traditional marking with the patient standing and transillumination marking with
      the patient horizontal were performed sequentially. METHODS: One hundred patients
      were sequentially examined prior to AP. The veins to be removed were mapped by
      the traditional way utilizing visual inspection and palpation in a standing
      position. They were then mapped in the supine or prone position utilizing a
      transillumination device specifically designed to enhance visualization of veins
      prior to venipuncture. RESULTS: In 100 out of 100 patients the markings performed
      using transillumination mapping most closely correlated with actual vein position
      during surgery. In addition, transillumination allowed for gauging of vein depth.
      CONCLUSIONS: Transillumination mapping significantly enhances the technique of
      ambulatory phlebectomy by more accurately visualizing the course of a varicose
      vein prior to extraction. Furthermore, sites for incisions or punctures are more
      accurately guided. As a result of this experience, it is now our routine practice
      to perform preoperative mapping for AP by transillumination in the horizontal
      position.

PMID- 9568202
TI  - Tumescent anesthesia in ambulatory phlebectomy.
AB  - BACKGROUND: Ambulatory phlebectomy is an elegant outpatient procedure for the
      removal of varicose veins. One of the keys to its success is the ability to
      perform the procedure under local anesthesia. A new form of anesthesia, tumescent
      anesthesia, has been developed for liposuction surgery and is now being expanded
      for use in other surgical disciplines. OBJECTIVE: To determine the efficacy and
      safety as well as review the use and advantages of tumescent anesthesia in
      ambulatory phlebectomy. METHODS: A retrospective review of phlebectomy cases
      performed in our offices under tumescent anesthesia. RESULTS: The reported level
      of intraoperative and postoperative pain was very low. The complication rate was
      consistent with other reports except for a higher number of hematomas (3.4%).
      CONCLUSIONS: Tumescent anesthesia provides a very safe, comfortable method of
      anesthetizing patients for ambulatory phlebectomy. Epinephrine, in appropriate
      concentrations, should be a part of all tumescent anesthetic solutions used for
      phlebectomy as it may decrease the incidence of hematoma.

PMID- 9568203
TI  - Ambulatory phlebectomy. Principles and evolution of the method.
AB  - BACKGROUND: An easy, effective, inexpensive, and aesthetic method of varicose
      vein avulsion, in an office setting, is the aim of most phlebologists. Muller's
      ambulatory phlebectomy probably comes very close to this goal. With the
      acceptance and diffusion of this method, imitations, deviations, and
      "ameliorations" are frequent but do not always represent a true evolution.
      OBJECTIVE: To describe the basic principles of the method and the evolution of
      some aspects (anesthesia, instruments, duplex mapping, eco-phlebectomy,
      compression) leading to effective advantages. CONCLUSION: In its 40 years in
      existence, ambulatory phlebectomy has not significantly changed, and has proved
      to be easy and safe. The most important progress has been made in anesthetic dose
      and in ultrasound applications.

PMID- 9568204
TI  - Muller's ambulatory phlebectomy for varicose veins of the foot.
AB  - BACKGROUND: Ambulatory phlebectomy is an accepted therapy for varicose veins. It
      has also been used for ankle and foot varicosities with success although the
      anatomy of the venous system of the foot is poorly described in the literature.
      OBJECTIVE: To review the relevant literature on the anatomy of the veins of the
      foot. Also to form an opinion on safe possibilities for the treatment of foot
      varicosis. METHODS: The English, French, German, and Dutch language literature
      was reviewed for anatomy and treatment of varicose veins of the foot. Fourteen
      patients (19 feet) were treated for varicose veins of the foot with ambulatory
      phlebectomy. RESULTS: Literature concerning the venous anatomy of the foot is
      very limited. Venous surgery, sclerotherapy, and ambulatory phlebectomy have all
      been used for the treatment of varicose veins of the foot. The former two have
      resulted in serious complications. All treated patients showed excellent results
      with ambulatory phlebectomy. No serious side effects were seen. CONCLUSIONS: The
      venous anatomy of the foot does not indicate major restrictions in the treatment
      of its varicosities. Ambulatory phlebectomy is the safest and most elegant
      treatment option for varicose veins of the foot. Venous surgery and sclerotherapy
      may be used successfully in special cases only.

PMID- 9568205
TI  - Muller's ambulatory phlebectomy and compression.
AB  - BACKGROUND: Compression therapy will relieve patients of symptoms of venous
      disease, if not prevent the occurrence of complications, and is used either alone
      or in combination with other treatment options. OBJECTIVE: To describe the use of
      compression in the two main therapy modalities: sclerocompression and ambulatory
      phlebectomy. METHODS: Aim and mechanism of compression therapy are analyzed and
      clinical implications are discussed. RESULTS: A modification of compression
      therapy after ambulatory phlebectomy is suggested based on empirical evidence.
      CONCLUSIONS: The use of broad compression pads after ambulatory phlebectomy
      reduces hemorrhage and enhances resorption.

PMID- 9568206
TI  - Combined high ligation and stab avulsion for varicose veins in an outpatient
      setting.
AB  - BACKGROUND: In recent years, the transition from radical surgery for the
      treatment of primary varicose veins has been modified from the previously
      described high ligation with complete stripping of the greater or lesser
      saphenous vein. OBJECTIVE: The purpose of the herewith-described technique is to
      present a less invasive technique that incorporates saphenofemoral ligation with
      hook avulsion of branch varicosities. METHODS: Sapheno-femoral ligation with hook
      avulsion of branch varicosities is carried out under local anesthesia utilizing
      the tumescent technique with dissection, ligation, and division of the greater
      saphenous vein and its tributaries. The hook avulsion procedure removes residual
      diseased venous segments. RESULTS: Patients treated by this combined ligation
      hook avulsion approach achieve excellent functional and clinical results
      associated with a minimal side effect profile. CONCLUSIONS: Combined flush
      sapheno-femoral ligation of normal saphenous veins (< 8 mm in diameter) and hook
      avulsion of branch tributaries produces excellent functional and cosmetic results
      with minimal morbidity.

PMID- 9568207
TI  - Red and blue telangiectasias: differences in oxygenation?

PMID- 9568208
TI  - Treatment of vulvar varicosities by injection-compression sclerotherapy.

PMID- 9568209
TI  - Actinic cheilitis.

PMID- 9568210
TI  - Scar tissue grafting.

PMID- 9568211
TI  - Master author and subject index, volumes 400-420.

PMID- 9568212
TI  - Emissary vein: an element of anomalous pulmonary venous connection.

PMID- 9568213
TI  - Regression of right ventricular dominance in the electrocardiogram after birth: a
      longitudinal follow-up of a healthy cohort from birth to 3 years.
AB  - To establish the incidence and course of right ventricular (RV) conduction delay
      during the regression of right ventricular dominance, 12 serial ECGs were
      recorded at regular intervals until age 36 months in a cohort of 43 normal
      neonates. Additionally, ECGs were recorded similarly in 6 infants from the age of
      1 month and in 7 from 2 months. The right precordial R waves were classified
      according to their amplitudes and their occurrence before or after the S wave. QR
      duration and its ratio to QRS were measured in right and left chest leads. The
      incidence of notched R waves, which is very rare in neonates, increased after the
      first month and occurred before the peak of R. Thereafter, the height of the
      notch decreased and then occurred after the peak of R. This turned into an r'
      (after the S wave) and finally the amplitude of r' decreased further and evolved
      into a notched S pattern. An rSR' or qRS pattern in the right precordial leads
      was never observed. An abnormal incomplete right bundle branch block during
      infancy can be distinguished from physiological right ventricular conduction
      delay by the unvarying amplitude of the R' wave, preceded by an S wave.

PMID- 9568214
TI  - Time course of myocardial amiodarone uptake in the piglet heart using a chronic
      animal model.
AB  - This investigation sought to study single dose pharmacokinetics of amiodarone in
      a chronic animal model. We developed a new chronic animal model that allows
      serial direct access to the heart of the immature piglet via an implanted acrylic
      thoracic window. Following instrumentation and 72-hour recovery, amiodarone (5
      mg/kg) was administered as a single intravenous bolus in immature piglets. Timed
      paired serum samples and myocardial biopsies for amiodarone level were obtained
      prior to, and up to 72 hours following, amiodarone administration. Peak
      concentrations of amiodarone in both serum (3.60 +/- 1.02 micrograms/ml) and
      tissue (84.2 +/- 6.50 ng/mg) occurred within 5 minutes of drug administration. As
      reported by others, this study demonstrated that the volume of distribution (VD)
      of amiodarone was large (33.31 +/- 35.21 L/kg), and the clearance (Cl) was low
      (13.6 +/- 4.4 ml/min/kg). Marked prolongation of both the serum t1/2 (29.98 +/-
      29.26 hours) and the myocardial t1/2 (29.20 +/- 29.49 hours) were noted as well.
      The early, rapid myocardial peak of amiodarone in the immature myocardium
      corresponds with recent clinical observations of onset of antiarrhythmic efficacy
      5 to 10 minutes following intravenous amiodarone administration in young
      children.

PMID- 9568215
TI  - Transcarotid balloon valvuloplasty with continuous transesophageal
      echocardiographic guidance for neonatal critical aortic valve stenosis: an
      alternative to surgical palliation.
AB  - Neonatal critical aortic valve stenosis is a life-threatening malformation if
      untreated. Before the late 1980s, the preferred treatment was surgical valvotomy;
      however, operative mortality was high. Early reports of transcatheter balloon
      dilation were encouraging, although femoral artery damage and aortic valve
      insufficiency were procedural limitations. With new balloon catheter technology,
      transumbilical, transvenous, and transcarotid approaches have been advocated,
      although a comparison with recent surgical results has not been performed. We
      compared all neonates who presented to our institution since 1985 with the
      diagnosis of critical aortic stenosis. Ten patients underwent surgical
      transventricular valvotomy and 13 patients underwent balloon valvuloplasty via a
      right carotid cutdown with continuous transesophageal echocardiographic guidance.
      Prior to intervention, all patients had either left ventricular dysfunction, an
      aortic valve gradient > 100 mmHg, significant mitral valve insufficiency, and/or
      ductal dependent systemic blood flow. All patients had successful relief of
      aortic valve obstruction with normalization of left ventricular function and
      successful discontinuation of prostaglandin E1. Use of continuous transesophageal
      echocardiographic guidance resulted in fluoroscopic exposure of only 12 +/- 8
      minutes. At the latest follow-up, a similar proportion of patients has required
      additional aortic valve procedures (38% vs 25%) and overall mortality (20% vs
      15%) is similar. In the transcarotid group, 9 of 13 patients (69%) have a normal
      appearing right carotid artery by Duplex imaging, and no neurologic events have
      been reported. Balloon aortic valvuloplasty via a right transcarotid approach is
      safe, simplifies crossing the valve, and is effective for the initial palliation
      of neonatal critical aortic stenosis. The use of transesophageal
      echocardiographic guidance reduces fluoroscopy exposure, enables accurate
      assessment of hemodynamics without catheter manipulation or angiography, and
      avoids femoral artery injury.

PMID- 9568216
TI  - Effects of age and respiration on right ventricular diastolic filling patterns in
      normal children.
AB  - Right ventricular diastolic filling was assessed in 88 normal Chinese children
      using Doppler echocardiographic interrogation of diastolic transtricuspid valve
      flow. Any influences of age and respiration on right ventricular diastolic
      filling were also investigated. The results showed that age-dependent differences
      were apparent for filling times, associated with the decrease in heart rate with
      increasing age. In addition, peak transtricuspid flow velocities were markedly
      greater in inspiration than in expiration, with corresponding increases in
      filling times and velocity-time integrals. The influence of age and respiration
      on transtricuspid flow parameters should be considered in the evaluation of right
      ventricular diastolic function by Doppler echocardiography. We believe that
      measurements should be standardized for respiratory phase and that right
      ventricular diastolic function parameters should be taken at end-inspiration and
      end-expiration, respectively.

PMID- 9568217
TI  - Persistent eustachian valves in infants: course and management in symptomatic
      patients.
AB  - Although commonly found on echocardiograms, persistent Eustachian valves rarely
      result in clinical symptoms in newborns and infants without other significant
      structural heart disease. Previous reports have suggested that such patients
      require surgical treatment. The goal of this study is to delineate better the
      clinical course in infants presenting with symptoms that are a result of
      persistent Eustachian valves. A review of all patients with symptoms attributed
      to persistent Eustachian valves over a 10-year period at Riley Hospital for
      Children showed 3 of 4 patients improved, with eventual resolution of symptoms,
      with conservative management alone. This suggests that, contrary to previous
      reports, clinical observation may be warranted in many of these infants.

PMID- 9568218
TI  - Effect of dexamethasone therapy on the neonatal ductus arteriosus.
AB  - Patent ductus arteriosus (PDA) is believed to be a contributing factor in the
      etiopathogenesis of bronchopulmonary dysplasia (BPD). We studied the effects of
      early dexamethasone therapy on persistent ductal patency and the role of PDA in
      the etiopathogenesis of BPD during the course of a randomized double-blind trial
      of dexamethasone to prevent BPD. Infants, who weighed between 700 and 999 g, had
      severe RDS, and had been given surfactant, were randomized to receive a 12-day
      course of dexamethasone (n = 13) or placebo (n = 17) starting within the first 12
      hours of postnatal life. The diagnosis of PDA was made clinically and was
      confirmed by cardiac ultrasound. The incidence of clinically significant ductus
      in infants who weighed less than 1000 g was 23% in the dexamethasone-treated
      group, as compared with 59% in infants who were given placebo. This difference
      was marginally significant, p = 0.05, odds ratio 0.21, 95% confidence interval
      0.04-1.05. None of the infants in the dexamethasone group had recurrence of PDA
      after indomethacin therapy as compared with three infants in the placebo group.
      Dexamethasone significantly reduced the number of days infants required
      ventilator and supplemental oxygen as compared with infants who received placebo.
      Dexamethasone, as compared with placebo, also reduced the incidence of BPD, p =
      0.025, odds ratio 0.08, 95% confidence interval 0.01-0.58. Dexamethasone may
      reduce the incidence of PDA in premature infants who weigh less than 1000 g at
      birth and thereby reduce the incidence of BPD.

PMID- 9568219
TI  - The natural course of isolated ventricular septal defect during adolescence.
AB  - Serial changes in patients with isolated VSD during adolescence have not
      previously been investigated. Hemodynamic status, diameter of the defect, and
      growth were studied yearly in 106 children with VSD. The mean duration of the
      follow-up was 13.16 years and ranged in 80% of subjects from 7 to 19 years (1395
      patients years). The mean ages at pre- and postpuberty were 8.62 and 16.67,
      respectively. The presented longitudinal study, in which losses due to death and
      operation were minimal (4%), ideally reflected the natural history of VSD.
      Although weight showed retardation during prepuberty, this lag was caught up by
      the end of adolescence. Stature showed no retardation in pre- and postpuberty.
      Cardiothoracic ratio decreased significantly from a mean of 0.48 to 0.44 and
      showed normal variation. Although the mean defect diameter at prepuberty was 5.33
      mm, this decreased to 2.7 postpubertally. The individual decrease (1.7 +/- 2.34
      mm) was significant (t = 5.349, p < 1/10(5)). The defect closed spontaneously in
      24 (22.6%). In the 75 patients without pulmonary hypertension and with mild left
      to-right shunting, 52 remained in the same class and spontaneous closure was
      observed in 23. In the 24 patients with moderate to severe left-to-right shunt,
      this decreased in 23 and only one remained stable. The 2 patients (1.9%) with
      Eisenmenger syndrome remained stable and 1 died. Aortic regurgitation developed
      in 10 patients (9.4%); however, this was of mild degree in most of them. No
      infective endocarditis was observed. It is concluded that patients with VSD
      should be followed closely through adolescence, because the diameter of the
      defect, as well as left-to-right shunting, can decrease, and it is concluded that
      the spontaneous closure of the defect is to be expected in a considerable 23%,
      and aortic prolapse or mild regurgitation may develop in approximately 10%.

PMID- 9568220
TI  - Immunosuppressive therapy of chronic myocarditis in children: three cases and the
      design of a randomized prospective trial of therapy.
AB  - Three infants, each with a clinical picture of dilated cardiomyopathy, underwent
      endomyocardial biopsy. Immunohistologic analysis revealed chronic myocarditis. In
      one infant, a postviral etiology of chronic myocarditis could be assessed on the
      basis of molecular techniques. Therapy with azathioprine and prednisone resulted
      in the normalization of echocardiographic findings. Based on these observations,
      a randomized, multicenter treatment study of chronic myocarditis in children
      (TCMC) has been initiated.

PMID- 9568221
TI  - The role of ductal constriction in transient stenosis of the left pulmonary
      artery.
AB  - To confirm the hypothesis that narrowing of the left pulmonary artery is produced
      by ductal closure, Doppler velocities in the pulmonary arteries from 20 premature
      infants with a patent duct were compared to velocities from 20 with a closed
      duct. In infants with a patent duct, the mean Doppler velocity in the main,
      right, and left pulmonary arteries were, respectively, 86 cm/sec +/- 5 standard
      error (SE), 120 +/- 7, and 125 +/- 8. With closed duct, the comparable velocities
      were 102 cm/sec +/- 7, 129 +/- 8, and 190 +/- 11. The only significant difference
      was the higher velocity in the left pulmonary artery associated with a closed
      duct (p = 0.00003). This physiologic origin of left-branch stenosis associated
      with ductal constriction should be considered when a murmur is detected after
      administration of indomethacin (in addition to possible persistent ductal flow),
      and as an explanation for some murmurs in the normal newborn. No anatomic or
      physiologic support was found for the theories that murmurs in the neonate were
      due to ductal flow, or to acute angulation of the branch pulmonary arteries.

PMID- 9568222
TI  - Atrioventricular septal defect with cor triatriatum: case report and review of
      the literature.
AB  - Atrioventricular septal defect with cor triatriatum is a rare combination, with
      only nine cases reported so far. Cor triatriatum, a potentially correctable cause
      of pulmonary arterial hypertension in atrioventricular septal defect patients,
      was missed in a few earlier case reports, leading to death and subsequent
      diagnosis at autopsy. We report the case of 3-year-old female child with this
      combination (partial atrioventricular septal defect with cor triatriatum) wherein
      the final diagnosis was made at cardiac catheterization. Successful surgical
      correction was performed.

PMID- 9568223
TI  - Premature "closing" of the foramen ovale in transposition of the great arteries
      with intact ventricular septum: rare cause of sudden neonatal death.
AB  - We report a male neonate who developed severe cyanosis and bradycardia at birth
      unresponsive to resuscitation. At autopsy he was found to have premature
      "closure" of the foramen ovale together with transposition of the great arteries
      and an intact ventricular septum. Reviewing the literature, we found only one
      case report describing a similar neonate with this lethal combination of cardiac
      malformations.

PMID- 9568224
TI  - Familial occurrence of congenital aneurysm of the muscular interventricular
      septum.
AB  - Congenital aneurysms of the muscular interventricular septum are rare. We report
      two brothers with this disease and their father, who had marked thinning of part
      of the muscular interventricular septum with paradoxical motion. These cases lend
      support to the idea that these aneurysms are the result of an inherited defect in
      the myocardium.

PMID- 9568225
TI  - Use of transvenous DDD pacing in a one-year-old with symptomatic hypertrophic
      cardiomyopathy.
AB  - Symptomatic hypertrophic cardiomyopathy (HCM) is rare in infants. Therapeutic
      options are limited and include beta-blocker or calcium-channel blocker therapy
      or surgical myotomy/myectomy. Atrioventricular sequential pacing has been
      utilized as an alternative to surgery in symptomatic adults with HCM. We report
      our results with transvenous dual chamber pacing in an infant with symptomatic
      HCM.

PMID- 9568226
TI  - Successful closure of the patent ductus arteriosus by indomethacin in an
      extremely low birth weight infant of very advanced postnatal age.
AB  - Many studies demonstrate the efficacy of closure of a patent ductus arteriosus
      with indomethacin, but also show that success diminishes markedly with increasing
      postnatal age. For this reason surgical ligation is usually preferred after the
      first month of life. We describe the case of a male premature infant (25 weeks
      gestation, birth weight 680 g), in whom a PDA was successfully closed with
      indomethacin (0.1 mg/kg once daily intravenously for 6 days) at the age of 11
      weeks. Thus it may be concluded that closure by drug may be attempted before
      surgical ligation even in cases of advanced postnatal age.

PMID- 9568227
TI  - CT and MRI findings in a child with constrictive pericarditis.
AB  - Constrictive pericarditis is rare in children. We report computed tomography (CT)
      and magnetic resonance imaging (MRI) findings in a 3-year-old girl. She had a
      swollen abdomen that increased in two months. CT and MRI showed a thickened
      pericardium (5.2 mm) without calcification. Both atria were enlarged and
      ventricles were relatively small. The engorged inferior vena cava had 2.8x the
      diameter of the descending aorta at the same level. Symptoms were dramatically
      improved after pericardiectomy. The histopathological features confirmed chronic
      pericarditis.

PMID- 9568228
TI  - Neonatal advanced heart block due to cardiac tumor.
AB  - We describe a unique case of a child who, since birth, has had a heart tumor at
      the atrioventricular junction associated with second degree atrioventricular
      block. The tumor is probably a rhabdomyoma.

PMID- 9568229
TI  - Hypertrophic cardiomyopathy with mitochondrial DNA depletion and respiratory
      enzyme defects.
AB  - We report the case of a child with severe hypertrophic cardiomyopathy, with
      decreased activity levels of cardiac mitochondrial respiratory complex I and III,
      and with a pronounced reduction in cardiac mitochondrial DNA copy number level.
      Mitochondrial DNA depletion has not been previously reported in hypertrophic
      cardiomyopathy and it may play a role in its pathogenesis.

PMID- 9568230
TI  - Right ventricular myocardial sinusoidal-coronary artery connections in critical
      pulmonary valve stenosis.
AB  - Ventriculo-coronary arterial connections are frequently observed in pulmonary
      atresia with intact interventricular septum. Sustained right ventricular
      hypertension during cardiac morphogenesis is thought to be responsible for
      persistence of myocardial sinusoidal-coronary artery connections. Considering an
      unusual observation of ventriculo-coronary arterial connections in a patient with
      critical pulmonary valve stenosis, we speculate that sinusoidal connections in
      pulmonary atresia with intact ventricular septum occur not only because it is the
      only exit for blood from the blind right ventricle, but also because of intrinsic
      altered morphogenesis of the right ventricle myocardium.

PMID- 9568232
TI  - Montelukast approved for asthma management.

PMID- 9568231
TI  - Propofol suppresses premature atrial contractions during anesthesia.

PMID- 9568233
TI  - CDC identifies immunizations needed by health care workers.

PMID- 9568234
TI  - Study poses new questions about calcium-channel blockers.

PMID- 9568235
TI  - JCAHO initiates Sentinel Event Alert.

PMID- 9568237
TI  - Health care spending growth at record low in 1996; prescription drugs break
      pattern with 9% increase.

PMID- 9568236
TI  - More than half of employers report steeper rise in pharmacy benefit costs than in
      overall medical costs.

PMID- 9568238
TI  - Adults over 60 depend heavily on pharmacists for guidance in medication use.

PMID- 9568239
TI  - Federal tax consequences of institutional pharmacy dispensing to outpatients.

PMID- 9568240
TI  - Infection in surgical patients: effects on mortality, hospitalization, and
      postdischarge care.
AB  - In-hospital mortality, length of stay (LOS), and level of postdischarge care in
      infected and noninfected surgical patients were studied. An analysis was
      conducted of a database that included diagnostic, procedure, and drug data
      collected when surgical patients were discharged from the hospital. Hospitals
      consisted of 90 nongovernment, nonspecialty, teaching, and nonteaching acute care
      hospitals of more than 100 beds. Patients in the database included 288,906
      patients of all ages hospitalized between July and September 1994. Patients
      selected of those who had undergone procedures likely to pose a moderate to high
      risk of infection. Of the 288,906 patients, 12,384 had undergone a moderate- to
      high-risk procedure; of these, 1,479 (11.9%) had had an infection during their
      hospitalization. Infection rates ranged from 1.9% to 25.4%, depending on the
      procedure. The in-hospital mortality rate in infected patients was 14.5%, versus
      1.8% for noninfected patients. Similarly, LOS in infected patients (median, 14
      days) was substantially greater than in noninfected patients (4 days). About 24%
      of infected patients required additional professional care after discharge,
      compared with 7% of noninfected patients. Infection occurs in a substantial
      portion of surgical patients and is associated with a higher death rate, longer
      hospitalization, and more intense postdischarge care.

PMID- 9568241
TI  - The journey to professional excellence: a matter of priorities.
AB  - Today and for the foreseeable future, it appears that we will confront continual
      challenges and almost overwhelming change that could easily disillusion and
      distract us from our primary purpose of patient care. To avoid that possibility
      and to ensure our continuing journey to excellence, let us remember and teach: It
      is always a matter of priorities.

PMID- 9568242
TI  - Inline filtration of ranitidine hydrochloride solutions.

PMID- 9568243
TI  - Mitochondrial biology, degenerative diseases and aging.

PMID- 9568245
TI  - Transfer of nuclear proteins to mitochondria--a role in mitochondrial disease.

PMID- 9568244
TI  - Mitochondrial diseases: genetics.

PMID- 9568246
TI  - Fatty acid metabolism in mitochondria: defects and genetics.

PMID- 9568247
TI  - Nuclear-mitochondrial intergenomic communication.

PMID- 9568248
TI  - Mitochondrial free radical damage and DNA repair.

PMID- 9568249
TI  - Problems in the diagnosis of mitochondrial cytopathies. Introduction.

PMID- 9568250
TI  - Biochemical methods for diagnosis of mitochondrial cytopathies: introduction and
      perspectives.

PMID- 9568251
TI  - Use of isolated mitochondria as a tool for biochemical characterization of
      neuromuscular disorders.

PMID- 9568252
TI  - Use of saponin-permeabilized muscle fibers for the diagnosis of mitochondrial
      diseases.

PMID- 9568253
TI  - Disturbances in mitochondrial transport systems leading to encephalomyopathies.

PMID- 9568254
TI  - Diagnosis of mitochondrial energy metabolism defects in tissue culture. Induction
      of MnSOD and bcl-2 in mitochondria from patients with complex I (NADH-CoQ
      reductase) deficiency.

PMID- 9568255
TI  - Ultrastructural alterations in encephalomyopathies of mitochondrial origin.

PMID- 9568256
TI  - Noninvasive approaches to mitochondrial myopathies: optical spectroscopy and
      imaging.

PMID- 9568257
TI  - Near-infrared spectrophotometry.

PMID- 9568258
TI  - Near-infrared spectroscopy in the diagnosis of mitochondrial disorders.

PMID- 9568260
TI  - The study of mitochondrial diseases using magnetic resonance spectroscopy.

PMID- 9568259
TI  - Introduction to magnetic resonance spectroscopy (MRS) and positron emission
      tomography (PET) for the investigation of mitochondrial myopathies.

PMID- 9568261
TI  - Correlative magnetic resonance and near-infrared technologies for the evaluation
      of mitochondrial disease.

PMID- 9568262
TI  - Positron emission tomography in mitochondrial diseases.

PMID- 9568263
TI  - Diet change in the management of metabolic encephalomyopathies.

PMID- 9568265
TI  - Leigh syndrome: historical perspective and clinical variations.

PMID- 9568264
TI  - Redox regulation of cell functions by alpha-lipoate: biochemical and molecular
      aspects.

PMID- 9568266
TI  - Biochemical defects and genetic abnormalities in cytochrome c oxidase of patients
      with Leigh syndrome.

PMID- 9568267
TI  - Mitochondrial diseases: clinical considerations.

PMID- 9568268
TI  - Simultaneous determination of creatine, uric acid, creatinine and hippuric acid
      in urine by high performance liquid chromatography.
AB  - A simple method for the simultaneous determination of creatine, uric acid,
      creatinine and hippuric acid in urine using reversed-phase high performance
      liquid chromatography was described. Chromatography was performed on a Nova-Pak
      C18 (3.9 x 150 mm) column with a mobile phase of 0.02 mol/L KH2PO4, and UV
      detection at 220 nm. The recoveries of creatine, uric acid, creatinine and
      hippuric acid were 103.13, 99.86, 98.26 and 98.24%, respectively. The calibration
      curves were linear within the concentration range of 2-200 micrograms/mL for
      creatine, uric acid and hippuric acid, and 2-400 micrograms/mL for creatinine.
      The detection limits of the method were 0.69, 0.21, 0.10 and 0.095 microgram/mL
      for creatine, uric acid, creatinine and hippuric acid, respectively. This method
      has been applied to the analysis of urine samples from normal subjects and some
      patients.

PMID- 9568269
TI  - Determination of nimesulide and hydroxynimesulide in human plasma by high
      performance liquid chromatography.
AB  - Two specific methods for the simultaneous determination of nimesulide, a non
      steroidal anti-inflammatory drug, and its hydroxylated metabolite in human plasma
      are described. Adopting a high performance liquid chromatographic (HPLC) system
      with UV detection (230 nm), the compounds, extracted from plasma in acidic
      medium, were separated on ODS columns under gradient conditions, using a
      phosphate buffer solution and methanol as mobile phase. For each method column
      length, gradient rate and composition were appropriately selected. The limit of
      quantitation was 25 ng/mL for both compounds. The two methods were validated by
      intra day assays at three concentration levels and applied in kinetic studies in
      healthy volunteers, during which inter-day assays were carried out confirming
      their feasibility.

PMID- 9568270
TI  - 3-Bromomethyl-propyphenazone as a new derivatization reagent for high performance
      liquid chromatography of captopril and hydrochlorothiazide with UV-detection.
AB  - 3-Bromomethyl-propyphenazone (BMP) was used as a derivatization reagent for the
      detection and quantification of captopril (CAP) and hydrochlorothiazide (HCT) by
      high performance liquid chromatography using Zorbax C8 column, and 0.05M sodium
      acetate, acetonitrile, methanol (14:17:4; pH 6.5) as mobile phase system with UV
      detection at 254 nm. The cited reagent reacts with the mercapto and amino groups
      of CAP and HCT in acetone using anhydrous potassium carbonate as hydrobromide
      acceptor. The reaction was completed within 30 min for CAP and 60 min for HCT
      with heating at 105 +/- 5 degrees C in mini-reaction vial. The linear
      concentration ranges for both CAP and HCT were 8 to 160 and 6 to 140 ng per
      injection, respectively. The derivatized captopril was synthesized and confirmed
      with spectral analysis. This method was applied for determination of spiked
      captopril in human urine after extraction with Extrelut-20 column using ethyl
      acetate:isopropanol (85:15 v/v) as eluant.

PMID- 9568271
TI  - Quantitative structure-retention relationship study of tetrazolium salts on
      alumina support.
AB  - The retention of 7 monotetrazolium and 9 ditetrazolium salts was determined on
      alumina and reversed-phase (RP) alumina layers using n-hexane-2-propanol and
      water-2-propanol mixtures as eluents. The retention capacity and the specific
      surface area of solutes in contact with the stationary phases were calculated.
      Quantitative structure-retention relationship calculations indicated that the
      retention capacity of solutes on RP alumina layers depended not only on the
      molecular hydrophobicity but also on the hydrogen-donor and acceptor properties.
      Specific surface areas were related to the electronic and steric parameters of
      the solutes. Calculations suggested that the retention on both alumina and RP
      alumina layers is of mixed character, hydrophobic, electronic and steric
      parameters are equally involved in the retention.

PMID- 9568272
TI  - High sensitivity determination of the remoxipride hydroquinone metabolite NCQ-344
      in plasma by coupled column reversed-phase liquid chromatography and
      electrochemical detection.
AB  - An HPLC method for the determination of NCQ-344, a remoxipride metabolite with a
      hydroquinone structure, in human plasma is described. Special precautions for the
      sampling were necessary as the compound rapidly decomposes. An efficient clean-up
      of the plasma samples was necessary to make use of the inherent sensitivity of
      the electrochemical detector. This was accomplished by a fast and simple liquid
      liquid extraction at pH 7.05 combined with further cleaning on-line by using a
      short cyanopropyl column as the first column in a column switching system. A
      heart-cut from the cyanopropyl column containing the NCQ-344 fraction was then
      injected onto the analytical octadecyl silica column and NCQ-344 was detected at
      an oxidation potential of 0.70 V. The absolute recovery was > 95% and
      concentrations down to 0.10 nM could be determined with acceptable precision. The
      NCQ-344 levels in a limited number of samples from patients given remoxipride
      were found to be between 0.10 and 1 nM. The remoxipride concentrations in the
      same samples were 5,000-20,000 nM.

PMID- 9568273
TI  - Determination of cyclohexamone after derivatization with 2,4-dinitrophenyl
      hydrazine in intravenous solutions stored in PVC bags by high performance liquid
      chromatography.
AB  - A high performance liquid chromatographic procedure is described for the
      determination of cyclohexanone leached in intravenous solutions from the
      poly(vinyl chloride) bags. After derivatization with 2,4-dinitrophenylhydrazine
      and extraction with pentane, the cyclohexanone derivative was analysed on a C18
      BDS Hypersil column using mobile phase mixture of acetonitrile:water (55:45).
      Ultra-violet detection was performed at 368 nm. The limit of quantification was
      30 ng/mL and the assay was linear from 0.05 to 50 micrograms/mL. The recovery was
      better than 95%. The proposed method is satisfactory in its accuracy and
      precision with particularly relative standard deviations (RSD) for intra-assay
      and inter-assay of below 10%. This method has been successfully used for the
      determination of cyclohexanone in aqueous solutions such as sodium chloride
      (0.9%) and glucose (5%) stored in PVC containers. The values obtained varied
      between 2.04 and 44.9 micrograms/mL according to solutions and volume.

PMID- 9568274
TI  - Enantiomeric separation and detection by high-performance liquid chromatography
      mass spectrometry of 2-arylpropionic acids derivatized with benzofurazan
      fluorescent reagents.
AB  - The enantiomneric separation and the detection of 2-arylpropionic acids after
      derivatization with the fluorescent reagents with a benzofurazan structure, (S)
      (+)-4-(N,N- dimethylaminosulphonyl)-7-(3-aminopyrrolidin-1-yl)-2,1,3-ben
      zoxadiazole ((S)-DBD-Apy), (R)-(-)-4-nitro-7-(3-aminopyrrolidin-1-yl)-2,1,3-
      benzoxadiazole ((R)-NBD-Apy), 4-N,N-dimethylaminosulphonyl-7-piperazino-2,1,3
      benzoxadi zole (DBD-PZ) and N-hydrazinoformylmethyl-N-methylamino-4,4- N,N
      dimethylaminosulphonyl-2,1,3-benzoxadiazole (DBD-CO-Hz) by high-performance
      liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI
      MS) were examined. The diastereomeric derivatization with (S)-DBD-Apy or (R)-NBD
      Apy and the separation on the reversed phase column afforded the high
      sensitivity. The separation on chiral stationary phase after non-chiral
      derivatization with DBD-PZ or DBD-CO-Hz provided less sensitivity. The signal-to
      noise ratio of (S)-DBD-Apy-(S)-ketoprofen of 200:1 was observed for 12.5 picomole
      (pmol) injection and selected ion monitoring (SIM) of the quasi-molecular ion
      after splitting 1:7 before entering into the electrospray ion sources. As a
      result, the usefulness of these reagents for MS detection has been demonstrated.

PMID- 9568275
TI  - Chromatography of medicinal plants and Chinese traditional medicines.
AB  - Applications of chromatographic techniques to medicinal plants and Chinese
      traditional medicines are outlined in this review. Areas involved are
      quantitation of active principles or index or principal components; quality
      evaluation of crude drugs; identification, characterization and preparative
      isolation of new compounds for medical use from plants; analysis of
      pharmaceutical preparations of plant origin and pharmacokinetic and
      pharmacological studies of herbal drugs and their preparations.

PMID- 9568276
TI  - Chromatographic analysis of polysaccharides extracted from Chinese Indocalamus
      tesselatus.
AB  - Three fractions of polysaccharides that have high biological activity were
      extracted from Chinese bamboo leaves (Indocalamus Tesselatus) with 0.9% sodium
      chloride, 1% ammonium oxalate and 85% ethanol. Their component sugars were
      investigated by paper chromatography developed with n-butanol-pyridine-water
      (6:4:3 by vol), and by gas chromatography with crown ester stationary-phase-fused
      silica capillary column. Their monosaccharide compositions are different from
      each other with glucuronic acid, galactose, arabinose, mannose, glucose, and
      xylose (52, 18, 9, 7 and 6%, respectively) in one fraction, only glucuronic acid
      in another and glucuronic acid, fucose, arabinose and xylose (36, 31, 24 and 9%,
      respectively) in the third fraction. The protection effect of two polysaccharides
      against experimental hepatitis was studied in mice.

PMID- 9568277
TI  - Determination of retinol, alpha-tocopherol, alpha- and beta-carotene by direct
      extraction of human serum using high performance liquid chromatography.
AB  - In this report we describe a modified reverse phase HPLC method that avoids the
      solvent evaporation step and allows simple and rapid determination of retinol,
      alpha-tocopherol, alpha-carotene and beta-carotene and achieves complete
      separation of alpha- and beta-carotene. Retinyl acetate, alpha-tocopheryl acetate
      and retinyl palmitate in ethanol were added to serum as internal standards. Serum
      was then deproteinized with an equal volume of ethanol, and the lipid was
      extracted with ethyl acetate-butanol (1:1 v/v). A portion of this solution was
      injected into a C18 reverse phase chromatographic column and absorbencies of the
      vitamins and internal standards were measured at 292 nm for tocopherols, 325 nm
      for retinoids and 450 nm for carotenoids; peak-height ratios were used to
      quantify each vitamin. The analytical recoveries for retinol, alpha-tocopherol
      alpha- and beta-carotene at various concentrations tested were 95-103, 90-98, 92
      99 and 94-96%, respectively. The intra- and interassay variations for low and
      high concentrations of retinol, alpha-tocopherol, alpha- and beta-carotene ranged
      from 2.4 to 6.7 for intraassay and from 4.3 to 8.5 for interassay replication.
      The detection limits were 1.25 (0.04), 19 (0.44), 0.35 (0.006) and 0.94 (0.017)
      micrograms/dL (delta mol/L) for retinol, alpha-tocopherol, alpha- and beta
      carotene, respectively.

PMID- 9568278
TI  - Simultaneous determination of chlorimuron-ethyl and its major metabolites in soil
      and water by reversed phase liquid chromatography.
AB  - A rapid reversed-phase HPLC method was developed for simultaneously determination
      of chlorimuron-ethyl and its metabolites such as ethyl-2-aminosulfonyl benzoate,
      4-methoxy-6-chloro-2-amino pyrimidine and saccharin in soil and water systems by
      using RP18 column and methanol-water (70:30 v/v) solvent system with detection at
      230 nm. The recoveries of chlorimuron-ethyl and its metabolites ranged from 80 to
      95%.

PMID- 9568279
TI  - Urinary NO2- and NO3- evaluation by an ion chromatography system.
AB  - We describe an ion chromatography system using a Dionex AS4A-SC column with
      carbonate-bicarbonate buffer (1.8-1.7 mM) as eluent for the evaluation of urinary
      NO2- and NO3-. This chromatographic system gives an accurate measurement of NO2-
      and NO3- in the urine as an index of NO production in vivo, making also possible
      to evaluate their relative proportion and providing useful tools to investigate
      the NO system.

PMID- 9568280
TI  - Branched-chain and unsaturated 1,7-diaminoheptane derivatives as deoxyhypusine
      synthase inhibitors.
AB  - Deoxyhypusine synthase catalyzes the first step in the posttranslational
      biosynthesis of the unusual amino acid hypusine [N epsilon-(4-amino-2
      hydroxybutyl)lysine] in eukaryotic translation initiation factor 5A (eIF-5A). eIF
      5A and its single hypusine residue are essential for cell proliferation. Two
      series of 1,7-diaminoheptane derivatives were prepared and tested as inhibitors
      of human deoxyhypusine synthase. These include branched-chain saturated
      derivatives and both branched- and straight-chain unsaturated derivatives
      providing size and positional variation in branching and different torsional
      constraints. Of the branched-chain compounds, 7-amino-1-guanidinooctane (39)
      proved to be the most potent inhibitor in vitro (IC50, 34 nM), while 1,7-diamino
      trans-hept-3-ene (20a) displayed the greatest inhibition (IC50, 0.7 microM) among
      the unsaturated compounds. Compound 39 also provided effective inhibition of
      hypusine production in Chinese hamster ovary cells in culture. Considerations of
      the in vitro inhibition data reported here, along with earlier findings, allowed
      some speculation concerning the conformation of the substrate spermidine during
      its productive interaction at the active site of deoxyhypusine synthase.

PMID- 9568281
TI  - 1,4-dihydro-2,3-quinoxalinediones as potential flavin metabolites and excitatory
      amino acid receptor ligands. Part 1: Synthesis and pharmacological evaluation of
      the benzylic oxidation series of 1,4-dihydro-6,7-dimethyl-2,3-quinoxalinedione.
AB  - A series of five 6,7-disubstituted 1,4-dihydro-2,3-quinoxalinediones was
      prepared, two of which are known microbial flavin metabolites and three of which
      are potential flavin metabolites. Four of the five compounds inhibited specific
      binding of [3H]-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid ([3H]AMPA),
      [3H]kainic acid, and [3H]6-cyano-1,4-dihydro-7-nitro-2,3-quinoxalinedione
      ([3H]CNQX) in rat brain homogenate fractions, with IC50 values in the low
      micromolar range (the fifth compound competed only with [3H]CNQX). Two of the
      compounds were moderately potent AMPA antagonists in an in vitro functional test.

PMID- 9568282
TI  - Chemical model studies on the monoamine oxidase-B catalyzed oxidation of 4
      substituted 1-cyclopropyl-1,2,3,6-tetrahydropyridines.
AB  - Two catalytic pathways have been proposed for the flavoenzyme monoamine oxidase B
      (MAO-B)--one based on an initial single electron transfer (SET) step from the
      nitrogen lone pair and the second based on an initial alpha-carbon hydrogen atom
      transfer (HAT) step. The SET pathway is consistent with the mechanism based
      inactivation properties of various cyclopropylamines. The observation that MAO-B
      catalyzes the efficient oxidation of certain 1-cyclopropyl-4-substituted-1,2,3,6
      tetrahydropyridines to the corresponding dihydropyridinium metabolites suggests
      that the catalytic pathway for these cyclic tertiary allylamines may not proceed
      via the putative SET generated aminyl radical cations. The present paper
      describes the chemical fate of a series of N-cyclopropyltetrahydropyridines
      examined under reaction conditions that model the SET and the HAT pathways. All
      of the test compounds were rapidly converted under HAT reaction conditions to
      their dihydropyridinium products. Although the test compounds also were oxidized
      rapidly under SET conditions, no evidence for dihydropyridinium product formation
      was observed. The products that were identified most likely were formed after
      cyclopropyl ring opening of the initially formed cyclopropylaminyl radical
      cation. The results are discussed in terms of the mechanism of MAO-B catalysis.

PMID- 9568283
TI  - Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole
      cells by CAAL peptidomimetics.
AB  - In this paper we describe the synthesis of a family of CAAL peptidomimetics as
      GGTase-I inhibitors. These inhibitors lack the central dipeptide AA in the key
      CAAL carboxy terminal sequence of geranylgeranylated proteins and are more
      selective for GGTase-I over FTase. In whole cells, these compounds are very
      potent inhibitors of the processing of the geranylgeranylated protein Rap1A
      without affecting the farnesylated protein H-Ras. One derivative, GGTI-298,
      inhibited cell division by blocking cells in the G1 phase of the cell cycle.

PMID- 9568284
TI  - Synthesis and evaluation of nitro 5-deazaflavin-pyrrolecarboxamide(s) hybrid
      molecules as novel DNA targeted bioreductive antitumor agents.
AB  - A series of 6-nitro-5-deazaflavins bearing at N(3) or N(10) position the
      pyrrolecarboxamide(s) group as DNA minor groove binder has been synthesized.
      These hybrid molecules show similar redox properties to those of 6-nitro-5
      deazaflavins with no pyrrolecarboxamide(s) group, suggesting that they generate
      stable one- and two-electron reduction product(s). Electrolytic reductions of the
      hybrid molecules were carried out at a controlled potential under anaerobic
      conditions in the presence of plasmid pBR322 DNA. Significant conversions of the
      supercoiled circular pBR322 DNA (form I) to the open circular DNA (form II) have
      been found by treatment with the reductively activated 6-nitro-5-deazaflavin
      derivatives. Their DNA damaging effects have been found to be enhanced as the
      number of pyrrolecarboxamide group as the DNA binder increases. Antitumor
      activities of the hybrid molecules towards KB and L1210 cells were evaluated in
      vitro. It has been found that the antitumor effects of the compounds on KB cells
      slightly change and those on L1210 cells decrease as the number of the
      pyrrolecarboxamide group increases. These results reveal that the combination of
      6-nitro-5-deazaflavin molecule with the pyrrolecarboxamide(s) group increase the
      DNA binding properties of the compounds, giving rise to promoted DNA damaging
      effects, and also suggest that the combination would affect the capacity of the
      compounds to act as the substrate for intracellular reductases and/or the
      cellular uptake of the compounds.

PMID- 9568285
TI  - Synthesis and hybridization properties of an acyclic achiral phosphonate DNA
      analogue.
AB  - Protected N-(2-hydroxyethyl)-N-(nucleobase-acetyl)aminomethanephosphonic+ ++ acid
      (6a-d) of all four DNA nucleobases have been prepared and oligomerized by solid
      phase synthesis. Four DNA decamers containing 1-10 of these 'PPNA' monomers were
      prepared and evaluated by Tm measurements (medium salt) for binding to their DNA
      and RNA complements. One central modification reduced the binding strongly (delta
      Tm = -10 degrees C), but contiguous PPNA monomers gave smaller effects, and the
      all-PPNA decamer bound to RNA with a delta Tm of -1.2 degrees C per modification.
      Thus PPNA oligomers are inferior DNA and RNA binders compared to the closely
      related and strongly binding PNA oligomers.

PMID- 9568286
TI  - Synthesis and vasorelaxant activity of 2-fluoromethylbenzopyran potassium channel
      openers.
AB  - The synthesis and vasorelaxant activity of 2-fluoromethylbenzopyran potassium
      channel openers are described. These (2-fluoromethyl) derivatives displayed
      smooth muscle relaxant activities comparable to or more potent than the
      corresponding 2-methyl analogues.

PMID- 9568287
TI  - Antioxidative and superoxide scavenging activities of retrochalcones in
      Glycyrrhiza inflata.
AB  - Licochalcone A, B, C, D and echinatin, retrochalcones isolated from the roots of
      Glycyrrhiza inflata (licorice), along with an ordinary chalcone
      isoliquiritigenin, were assessed for their inhibitory activities on lipid
      peroxidation in various systems and radical scavenging activity. Among those
      tested, licochalcones B and D strongly inhibited superoxide anion production in
      the xanthine/xanthine oxidase system. These two compounds also showed potent
      scavenging activity on DPPH radical. Microsomal lipid peroxidation induced by
      Fe(III)-ADP/NAPDH was inhibited almost completely by 3 micrograms/ml of
      licochalcones B and D. Mitochondrial lipid peroxidation induced by Fe(III)
      ADP/NADH was more sensitive to these retrochalcones; almost complete inhibition
      was observed at 10 micrograms/ml of all retrochalcones tested. Licochalcones B
      and D scavenged superoxide anion in microsome. Furthermore, these retrochalcones
      protected red cells against oxidative hemolysis. These phenolic compounds were
      shown to be effective to protect biological systems against various oxidative
      stresses.

PMID- 9568289
TI  - Discovery and structure--activity relationship studies of a novel and specific
      peptide motif, Pro-X-X-X-Asp-X, as a platelet fibrinogen receptor antagonist.
AB  - A novel hexapeptide, H-Pro-Ser-Nva-Gly-Asp-Trp-OH 6, a specific antagonist of
      platelet fibrinogen receptor (GpIIb/IIIa), was discovered in a structure-activity
      relationship (SAR) study where the role of the N-terminal Pro moiety of an RGD
      containing peptide, H-Pro-Ser-Arg-Gly-Asp-Trp-OH 1, which is a potent but not
      specific antagonist toward GpIIb/IIIa integrin, was investigated. This novel
      peptide 6 exhibits very high activity as a human platelet aggregation inhibitor
      (IC50 0.59 microM, human PRP/collagen) as well as marked specificity for
      GpIIb/IIIa. A series of substitutions at the third position (Nva residue) in this
      hexapeptide, focused on the conformational rigidity, led to compounds which are
      superior to the original novel peptide 6 with regard to anti-platelet activity.
      The peptides, H-Pro-Ser-Hyp-Gly-Asp-Trp-OH 17 and H-Pro-Ser-delta Pro-Gly-Asp-Trp
      OH 18 with the 5-membered ring structure, which restricted the conformation of
      the peptide backbone at the third position, inhibited the aggregation of human
      platelets at submicromolar concentrations (IC50 0.39 and 0.30 microM,
      respectively). Further structure-activity relationship studies at each position
      of the peptide sequence suggest a novel motif sequence, Pro-X1-X2-X3-Asp-X4, for
      specific GpIIb/IIIa integrin recognition, in which the N-terminal free Pro
      residue and the Asp residue at the fifth position are essential to the activity.
      This motif sequence is summarized as follows: (1) a small amino acid such as Ser,
      Ala or Gly is preferable at X1 position; (2) X2 may be any amino acid, preferably
      a bulky amino acid such as Tle or a cyclic amino acid such as Pro; (3) X3 must be
      a small amino acid such as Gly; and (4) X4 is preferably an amino acid with an
      aromatic side chain.

PMID- 9568288
TI  - Synthesis of new pyrrolo[1,2-d][1,2,4]triazines and thiazolo[3,4
      d][1,2,4]triazines as immunostimulating agents.
AB  - Four pyrrolo[1,2-d][1,2,4]triazines and four thiazolo[3,4-d][1,2,4]triazines were
      synthesized from trans-4-hydroxy-L-proline and L-thiaproline, respectively. The
      synthetic route involved formation of hydrazides followed by cyclization with
      orthoesters. The proliferative response to human lymphocyte mitogen
      (phytohemagglutinin) revealed significant immunostimulant activity for all test
      drugs. Furthermore, some triazine derivatives were effective to activate
      production of free oxygen radical by phagocytes in response to stimulation by
      opsonized zymosan.

PMID- 9568290
TI  - Gordon Memorial Lecture. A holistic view of poultry science from a reductionist
      perspective.
AB  - 1. The success of the poultry industry has been dependent upon development of a
      precise understanding of poultry biology. 2. The advent of tools and probes that
      reveal the molecular and cellular organisation of complex physiological systems
      should be embraced by the poultry industry to gain insights into recurring
      problems such as egg shell quality and ascites. 3. The ability to modify the
      genome of chickens provides an opportunity to breed chickens with unprecedented
      precision. 4. The judicious use of time and resources will require a working
      knowledge of molecular and cellular biology and the poultry industry. There is an
      urgent need for educational facilities that provide both perspectives.

PMID- 9568291
TI  - Long term effects of boron on layer bone strength and production parameters.
AB  - 1. The effects of dietary boron (0, 50, 100, 200, and 400 mg/kg) on bone strength
      characteristics and egg production of white leghorn layers were investigated. 2.
      The shear fracture energy increased in the tibia and radius at 72 weeks for birds
      started on the 200 mg/kg supplement at 32 weeks of age. 3. The shear force,
      stress, and fracture energy of the tibia and radius increased for the non-egg
      producing birds at 72 weeks. 4. Bird body weight, food consumption, egg weight,
      and egg production all decreased at 400 mg/kg boron. 5. Boron concentrations in
      the breast, liver, thigh and bone tissue increased with increasing concentrations
      of supplemental boron.

PMID- 9568292
TI  - A preliminary estimate of the heritability of plasma troponin T in broiler
      chickens.
AB  - 1. Male and female broiler chickens of a pure line were selected over one
      generation for low or high plasma, cardiac-derived troponin T concentrations at
      12 h of age. 2. Heritability of plasma troponin T was moderately high (h2 = 0.38
      +/- 0.06), and there was no difference in mean body weights of parents (G0) of
      the 2 lines at 4 and 19 weeks of age. 3. This preliminary study suggests that
      broiler breeder companies will be able to select for resistance against heart
      damage and ascites.

PMID- 9568293
TI  - Donor primordial germ cell-derived offspring from recipient germline chimaeric
      chickens: absence of long-term immune rejection and effects on sex ratios.
AB  - 1. Germline chimaeric chickens were produced by the transfer of primordial germ
      cells, and the generation of donor-derived offspring was examined for a maximum
      of 146 weeks. 2. The frequencies of donor-derived offspring from the chimaeras
      were 47% to 97%, and no apparent changes in frequency were observed with
      increasing age during the test period. 3. Differentiation of donor primordial
      germ cells into functional gametes appeared to be restricted to a degree at some
      developmental stage in the gonads of chimaeric chickens of the opposite sex.

PMID- 9568294
TI  - Reducing growth rate of broiler chickens with a low energy diet does not improve
      cortical bone quality.
AB  - 1. Reducing growth rate is often supposed to allow better skeletal development
      and improve bone quality. In order to test this assumption, flocks of broiler
      chickens fed on a diet containing 13.31 MJ ME/kg (H) were compared with flocks in
      which the growth rate was reduced by feeding birds with a low energy diet (L,
      9.62 MJ ME/kg). 2. Bone growth was studied in 2 experiments in order to identify
      any changes in bone tissue of slow-growing chickens that might explain why they
      are less predisposed to varus-valgus deformities (3.1% vs 19.9%). 3. In
      experiment 1, the morphology, composition and histomorphometry of the tibiotarsi
      were analysed in both groups at 1, 12, 26, 42 and 46 d of age. Tibial variables
      (weight, volume, length, cortex size and structure, dry content and ash
      percentage) were always reduced in slow-growing birds except at 42 d of age, when
      tibial weight and cortex areas were similar in both groups. 4. Every variable was
      similar in both groups, or even higher in H birds, when chickens were compared at
      similar body weight, suggesting that the low growth rate did not improve bone
      quantity or quality of the tibiae. 5. In experiment 2, the composition of the
      tibiotarsi was compared every 2 days during the first week and twice a week until
      36 d of age, in H and L birds. Weight and composition of the tibiotarsi did not
      differ between groups when compared at equal body weight, as also shown in
      experiment 1. 6. The reduced occurrence of varus-valgus deformities in slow
      growing chicks cannot be related to an improvement in the structure and the
      composition of their bone tissue.

PMID- 9568295
TI  - Factors affecting direct and correlated responses in a White Leghorn population
      under long-term selection for egg number.
AB  - 1. Data on 13,773 pullets, the progeny of 30 to 50 sires and about 135 to 220
      dams per generation of a strain of White Leghorn under long-term selection for
      part period egg production over 16 generations, were examined. 2. Realised
      genetic gain per generation was highly significant for egg production (2.55
      eggs), egg weight (-0.51 g), age at sexual maturity (-2.30 d) and 40 week body
      weight (-11.73 g). 3. The significant genetic response of 4.46 to 4.72 eggs per
      generation was realised in the first 8 generations only, which was accompanied by
      a marked decline in egg weight (-1.67 and -0.79 g per generation) and in age at
      sexual maturity (-4.63 and -6.39 d per generation). The 20 and 40 week body
      weights showed significant improvement in the last 4 generations. 4. Realised
      heritabilities were much lower in the last 8 than in the first 8 generation. 5.
      The additive genetic variance for most traits, except 20 week body weight and
      genetic covariances of egg production with egg weight and age at sexual maturity,
      declined significantly. 6. Natural selection did not seem to play any major role.
      No appreciable change in fitness traits was observed in the selected line. 7. The
      time trends were non-significant for all the traits in the control line,
      indicating its stability over generations.

PMID- 9568296
TI  - Association of endogenous viral genes with quantitative traits in chickens
      selected for high egg production and susceptibility or resistance to Marek's
      disease.
AB  - 1. The association of endogenous viral (ev) genes with quantitative traits in 2
      genetically distinct sets of White Leghorn strains were investigated. Strain S
      had been selected for susceptibility to Marek's disease (MD) whereas strain K had
      been selected for resistance to MD and high egg production and egg weight. 2. In
      all, 8 ev genes were typed. Ev10, ev19 and 'newB' occurred exclusively in strain
      S, 'newA' occurred only in strain K, and ev1, ev3, ev6 and ev8 occurred in both
      strains. 3. Whereas ev6 and ev8 were associated with reduction in egg production
      rate in strain S, in strain K, the presence of ev3 was associated with increased
      group specific antigen. 4. The genetic background of the chicken strain may play
      a role in the way certain ev genes affect traits. 5. It was thought that the
      position of ev genes on the chromosome may be important and their association
      with traits of economic importance make them potential genetic markers for
      uncovering quantitative trait loci.

PMID- 9568297
TI  - Effectiveness of two fluoroquinolones for the treatment of chronic respiratory
      disease outbreak in broilers.
AB  - 1. Chronic respiratory disease (CRD) caused by Mycoplasma synoviae in association
      with Escherichia coli is the disease most frequently encountered in poultry in
      Mexico. 2. Differences of antimycoplasmal activity, pharmacokinetics and cost
      among fluoroquinolones were the impetus for this clinical evaluation of efficacy
      of enrofloxacin and norfloxacin-nicotinate in broilers with CRD. 3. A total of
      99,600 broilers, naturally infected with M. synoviae and E. coli, were treated
      with enrofloxacin (10 mg/kg/d for 3 d) (n = 49,800) or norfloxacin-nicotinate (20
      mg/kg/d for 3 d) (n = 49,800). 4. Based on survivor analysis, there were no
      significant differences of efficacy of the 2 drugs. Survivor probabilities were
      above 0.99. 5. These results indicate that enrofloxacin and norfloxacin
      nicotinate are efficacious for treatment of CRD. Questions remaining to be
      answered by other studies include: public health concern about the use of
      fluoroquinolones for the treatment of CRD; clinical superiority of one of these
      drugs on the basis of an attribute other than antimicrobial activity, such as
      cost:benefit ratio or ability to prevent bacterial resistance. 6. Clinical
      efficacy is not a relevant variable in assessing whether norfloxacin-nicotinate
      or enrofloxacin should be used for the treatment of CRD associated with E. coli
      in broilers.

PMID- 9568298
TI  - Elimination of oxolinic acid in eggs after oral treatment of laying hens.
AB  - 1. Oxolinic acid is often used in poultry as a therapeutic agent. The aim of this
      study was to determine both its elimination into eggs, following oral dosing
      through the drinking water (12 mg/kg/d) or diet (13 mg/kg/d) for 5 d and its
      plasma concentrations. 2. Samples (albumen, yolk, plasma) were analysed by high
      performance liquid chromatography (HPLC) with fluorimetric detection. The limits
      of quantification were 10 ng/g in plasma and 5 ng/g in albumen and yolk. Residues
      were much higher in albumen than in plasma, whereas they were lower in yolk. 3.
      95% of the overall oxolinic acid detected in eggs was concentrated in the
      albumen. 4. Detectable residues persisted for 9 d and 7 d, respectively, in
      albumen and yolk after the treatment was discontinued.

PMID- 9568299
TI  - Hen age and fatty acid composition of egg yolk lipid.
AB  - 1. Total lipid, total cholesterol, and phospholipid contents per gram of egg yolk
      were found to be the same for eggs from 21 and 57 week-old hens. 2. In contrast,
      fatty acid composition of total egg yolk lipid was different for the 2 groups of
      hens. The contents of long-chain (20 C and 22 C) polyunsaturated fatty acids of n
      6 and n-3 series were 20% to 25% higher in egg yolks from the younger hens. 3.
      This finding is discussed with respect to the nutritional value of eggs from hens
      of different ages regarding the use of egg yolk lipid in the production of infant
      formulae.

PMID- 9568300
TI  - Effect of dietary oat administration on lipid stability in broiler meat.
AB  - 1. The susceptibility to oxidation of meat from broilers receiving 200 g/kg oats
      in the diet was compared to the stability of meat from broilers receiving a
      control diet (10 mg/kg of alpha-tocopheryl acetate) and a diet enriched in alpha
      tocopheryl acetate (200 mg/kg). 2. After 9 d of refrigerated storage
      thiobarbituric acid-reactive substances (TBARS) values in raw dark meat (thigh)
      were 0.51 and 0.19, respectively, for broilers fed on the control and the alpha
      tocopheryl acetate-enriched diets. Meat from broilers fed on the diet containing
      oats had a lower TBARS value than the control group (P < 0.05), but higher than
      the group receiving the supplemented diet. The same trend was observed in white
      meat (breast). Similar effects were observed after the frozen storage of meats,
      although the antioxidant effect of oats was more evident (P < 0.05) than in the
      raw meat. 3. Cholesterol oxidation products (COPS) in broiler meat were also
      influenced by the dietary regimen. COPS concentration in white and dark meat,
      respectively, from broilers fed on the oat diet were 43% and 32% lower than those
      in the control samples. 4. Supplemental alpha-tocopheryl acetate reduced COPS
      concentration by approximately 60%. The availability of natural antioxidants and
      their possible synergistic effects suggest an interesting way of improving meat
      stability.

PMID- 9568301
TI  - Evaluation of oligonucleotide probes for simple tandem repeats (STR) to produce
      informative DNA fingerprints of the chicken.
AB  - 1. DNA fingerprints of chickens from 2 commercial lines were used to identify
      oligonucleotide probes providing informative DNA fingerprints. 2. The
      oligonucleotides [CA]8, [CAC]5, [GGAT]4 and [GACA]4, producing a high number of
      bands of sufficient intensity and regular distribution, were chosen for further
      analysis out of 10 tested. 3. Analyses of banding patterns within families
      revealed Mendelian inheritance of the fragments detected. The DNA fingerprints
      obtained with the 4 chosen oligonucleotide probes showed about 40 scorable bands
      in total. 4. Comparison of banding patterns within and between the chicken lines
      for all 4 oligonucleotide probes revealed levels of bandsharing which did not
      differ significantly. The number of loci detected by these probes ranged from 25
      to 30 each. 5. The probes [CA]8, [CAC]5, [GGAT]4 and [GACA]4 can be used to
      produce informative DNA fingerprints of chicken. These probes provide estimates
      of the genetic similarity/variability of individuals or of populations and
      provide a valid measure of the actual degree of genetic similarity/variability.

PMID- 9568302
TI  - Linear model of nitrogen balance and examination of the nature of true
      metabolisable energy and its nitrogen corrected form.
AB  - 1. The nature of nitrogen (N) corrected true metabolisable energy (TMEN) was
      derived using a linear model of N balance, constructed from the relationship
      between excreted and ingested N. 2. TME was described in terms of a regression
      line, formed from 'fed' points relating energy voided to energy ingested (GE), as
      GE - (afed + bGE) + afast. On assignment of theoretical excreta and ingested
      energy components, a deviation from conceptual metabolisable energy (MEc), equal
      to the difference between afed and afast, was established and attributed to
      metabolic urinary energy (UmE). 3. The N balance model is based on the form of
      relationship between N excreted and N ingested (NI) that exhibits a linear
      deviation at 'initial' rates of N ingestion. The model postulates the following:
      The deviation is the result of a sparing effect of ingested N on the N component
      of UmE, viz. metabolic urinary N (UmN); The magnitude of UmN, through 'initial'
      values of fed N, is described by an intercept component, aNp, and a slope
      quantity, -(bNr - bNna) NI, where bNna and bNr are respectively the slopes of N
      excretion through 'initial' and 'subsequent' rates of ingested food N; The
      magnitude of the deviation from zero nitrogen balance (ZNB) through 'initial' and
      'subsequent' rates of ingested N is the sum of the previous terms and aNm - (1 -
      bNr) NI, where aNm is the intercept component representing maintenance losses of
      N at fasting and (1-bNr) NI is the quantity of fed N retained to replace
      maintenance N loss. 4. Application of the appropriate energetic forms of UmN and
      aNm, viz. Et aNp - Et (bNr - bNna) NI and EuaNm, to the expression for obtaining
      TME, demonstrated that TME exceeded MEc by the quantities Et (bNr - bNna) NI and
      Et aNp, for test food intakes resulting in 'initial' and 'subsequent' rates of
      food N, respectively. 5. Application of appropriate energetic components of the
      model to simulate correction of TME to ZNB, demonstrated TMEZNB to be a biased
      quantity, deviating from MEc by the amount -Eu (1 - bNr) NI or expressed as an
      excreta energy slope component, [formula: see text] where Eu is an appropriate
      energy coefficient. An alternative perspective is that ZNB correction removes the
      energetic form of UmN as a source of bias, but introduces one related to EuaNm.
      Its nature may be perceived by regarding TME as a function of a regression line
      relating energy excreted (EE) to energy ingested that has been corrected for UmN
      energetic bias and is pivoting on a fulcrum vertically aligned with the position
      of ZNB on the GE (x) axis. The regression line rotates anti-clockwise in response
      to ZNB correction by an amount equal to the magnitude of EuaNm measured on the EE
      (y) axis from the point of interception. 6. The study identified processes that
      may be employed to remove bias and improve precision of TME.

PMID- 9568303
TI  - Energy balance of laying hens selected on residual food consumption.

PMID- 9568304
TI  - Use of industrial amino acids to allow low protein concentrations in finishing
      diets for growing Muscovy ducks.
AB  - 1. Three experiments were performed to assess the effects of decreasing protein
      concentration in the finishing diets for growing Muscovy ducks (8 to 12 weeks of
      age) by adding 4 essential amino acids (AAs, lysine, methionine, threonine and
      tryptophan). Experimental diets with crude protein (CP) contents from 105 to 142
      g/kg, were compared with control diets providing 150 to 160 g/kg CP. In each
      trial, all diets were isocaloric. No significant modification in growth or
      carcase quality was observed when CP was greater than 124 g/kg in diets
      supplemented with the 4 essential AAs. 2. There was no advantages in supplying
      more than 4.3 g of digestible lysine per kg of diet (12.75 MJ ME/kg). When
      threonine was not added, breast yield decreased significantly (-4.3%), while
      omitting tryptophan supplementation did not influence performance. 3.
      Furthermore, the experiments confirmed that reducing CP had little or no effect
      on food conversion efficiency and fatness in Muscovy ducklings, unlike the
      observed situation in broiler chickens.

PMID- 9568305
TI  - Influence of growing season, tannin content and autoclave treatment on the
      nutritive value of near-isogenic lines of faba beans (Vicia faba L.) when fed to
      leghorn chicks.
AB  - 1. The objective of this study was to determine the influence of heat-treatment
      (autoclaving) on the utilisation by chicks of near-isogenic lines of faba beans
      that were either tannin-free (Winter-white or Spring-white) or had tannins in the
      seed coat (Winter-coloured or Spring-coloured). The effect of heat treatment on a
      common tannin-containing cultivar, Diana, was also studied. 2. The nitrogen
      corrected apparent metabolisable energy (AMEn) values of diets containing 600 g
      faba beans/kg diet were affected by tanning content and autoclave treatment of
      faba beans, with 59% of total variance in AMEn being attributable to the effect
      of autoclaving. The AMEn values were 9% higher for chicks fed on the autoclaved
      compared with those fed on diets containing the raw faba beans, 5% higher for the
      near-isogenic faba beans with no tannins compared with those with tannins, and 4%
      higher for the Winter compared with the Spring cultivars. 3. The above study was
      carried out on droppings obtained by total collection. Similar but not identical
      trends were obtained when AMEn was calculated using the chromic oxide index
      method (r = 0.91). 4. Both autoclaving and the use of tannin-free faba beans
      improved the apparent protein digestibility (APD) of the diets by similar amounts
      (4% as determined by the total collection method and 6% as determined by the
      chronic oxide index method). 5. The digestibility of most amino acids either
      alone or together was affected by a cultivar x tannin x processing interaction.
      The cultivar by tannin interaction demonstrated that autoclaving increased the
      digestibility of amino acids to a greater degree when the tannin-containing (for
      example, 9% for lysine) than when the tannin-free faba beans (4% for lysine) were
      used in the diets. 6. The improvements in AMEn, APD and total amino acid
      digestibilities of faba beans following heat treatments ranged from 18% to 33%,
      5% to 16% and 5% to 11%, respectively. The results demonstrate that the method of
      analysis can affect the values obtained but that they do not change the overall
      pattern of results. The results also suggest that, in most cases, more than half
      of the response to heat treatment is associated with the inactivation of tannins
      while the balance of the response is attributable to an effect of heat treatment
      on the non-tannin-containing factors. In summary, heat treatment can improve the
      utilisation of faba bean by chickens especially when they contain tannins. 7.
      Chicks, unlike rats, do not seem to adapt to tannins as the excretion of 3 amino
      acids that are the main constituents of a proline-rich protein were not affected
      by dietary tannins.

PMID- 9568306
TI  - Influence of high dietary vitamin E supplementation on egg production and plasma
      characteristics in hens subjected to heat stress.
AB  - 1. The effects of different dietary concentrations of vitamin E (alpha-tocopherol
      acetate) were investigated in 2 experiments on laying hens exposed to chronic
      heat stress at 32 degrees C. 2. In the first experiment, egg production and
      plasma concentrations of calcium and egg yolk precursors were measured in 24 hens
      before, during and after a stress period of one week and fed on diets containing
      10 or 500 mg vitamin E/kg. 3. In the second, larger experiment, egg production
      and food intake were measured in 300 hens housed in 2 temperature-controlled
      rooms and fed on diets containing 10, 125 or 500 mg vitamin E/kg. Birds in room 1
      were stressed from 24 to 28 weeks of age and those in room 2 from 32 to 36 weeks.
      4. In experiment 1, egg production and egg weight were significantly higher (72.6
      vs 51.2%, P < 0.05 and 66.6 vs 63.1 g, P < 0.005 respectively) during and after
      the period of stress in the group given 500 mg vitamin E/kg. Plasma
      concentrations of calcium, vitellogenin (zinc) and VLDL (triglyceride) were also
      higher in this group. 5. In experiment 2, egg production was significantly higher
      (65.4 vs 56.2%, P < 0.05) during and after the period of heat stress in birds in
      room 1 fed on the diet containing 500 mg vitamin E/kg. Egg production was also
      higher (49.9% vs 44.7%) on this treatment during the stress period in room 2,
      though the difference was not significant (P < 0.10). Egg weight and food intake
      were unaffected by treatment in either room. 6. It is concluded that dietary
      supplementation with extra vitamin E can, at least in part, alleviate the adverse
      effects of chronic heat stress in laying hens, perhaps by maintaining the supply
      of egg precursors in plasma.

PMID- 9568307
TI  - Order of amino acid limitation in poultry by-product meal.
AB  - 1. Two chick assays (from 8 to 17 d posthatching) were conducted to determine the
      order of amino acid (AA) limitation in poultry by-product meal (PBPM) using AA
      deletion and addition assays. 2. In the deletion assay, the basal diet contained
      155 g/kg crude protein (provided solely by PBPM) and was fortified with cystine,
      tryptophan, threonine, lysine, valine, isoleucine, histidine, methionine and
      phenylalanine to meet the Illinois ideal AA Pattern. Each AA was then deleted
      individually from the basal diet and its effect on growth assessed. 3. In the
      addition assay, various individual or combined additions of nine AAs were made to
      an unfortified 155 g/kg crude protein diet containing PBPM as the sole source of
      dietary crude protein. 4. The results from the deletion assay were in general
      agreement with those from the addition assay. Based on the combined results of
      the deletion and addition assays, the order of AA limitation in PBPM was 1)
      cystine, 2) tryptophan, 3) threonine and lysine, 5) valine, and 6) isoleucine and
      histidine with the degree of deficiency of valine, isoleucine and histidine being
      similar. The results also suggested that methionine may be slightly limiting in
      PBPM protein.

PMID- 9568308
TI  - Combined effects of clenbuterol and various concentrations of protein on
      performance of broiler chickens.
AB  - 1. The effects of the beta-adrenergic agonist, clenbuterol (1 mg/kg diet) on the
      growth and muscle composition in female broiler chickens (14 to 32 d of age) fed
      on diets containing various concentrations of protein (220, 240 or 260 g
      protein/kg) were examined. 2. Body weight gain over the 18 d period increased
      linearly with increasing protein intake. The rate of gain was significantly
      higher in clenbuterol-treated chickens than in control birds. 3. Dietary
      clenbuterol increased thigh muscle weight and protein concentration of breast and
      thigh muscle, regardless of dietary protein content. Protein/DNA ratio in thigh
      muscle was enhanced by clenbuterol feeding, and the magnitude of difference of
      the ratio was higher in chickens fed on the 240 and 260 g CP/kg diets than in
      those fed the 220 g CP/kg diet. 4. It was concluded that clenbuterol-treated
      chickens require increased dietary protein to maintain maximal growth, and that
      increased protein consumption is an important factor in improving growth in
      clenbuterol-fed broilers.

PMID- 9568309
TI  - Effects of corticotropin releasing factor on the production of
      adrenocorticotropic hormone by leukocyte populations.
AB  - 1. Corticotropin-releasing factor (CRF), a neuropeptide with immunomodulating
      properties, is known to stimulate avian splenic leukocytes to produce
      adrenocorticotropic hormone (ACTH). 2. The present study was to determine which
      avian splenic leukocyte subpopulation(s) produce ACTH in response to CRF
      stimulation. 3. Splenic leukocytes from 8-week-old male chickens were isolated on
      Histopaque 1077 and macrophages were separated from lymphocytes by adherence to a
      polystyrene surface. 4. Different concentrations of CRF (0, 5, 50, 500 or 1000
      ng/m) were incubated with the different leukocyte populations, supernatants were
      collected and ACTH was measured using a radioimmunoassay. 5. Isolated
      macrophages, stimulated with CRF, produced significantly more ACTH than either
      unstimulated macrophages or CRF-stimulated lymphocytes, suggesting that ACTH may
      be produced by a particular subset of leukocytes, the macrophages (and
      monocytes), in response to CRF stimulation.

PMID- 9568311
TI  - Thermoregulation in naked neck chickens subjected to different ambient
      temperatures.
AB  - 1. Heterozygous (Na/na) naked neck chickens and their normally feathered (na/na)
      sibs, were exposed to constant ambient temperatures (Ta) ranging between 15 and
      35 degrees C and 12h: 12h diurnal high:low temperatures of 15 degrees C:35
      degrees C. 2. No significant effect of genotype was obtained in weight gain and
      food intake. However, the naked neck birds tended to gain somewhat more weight at
      high Ta and consume more food at low Ta. 3. At 35 degrees C Na birds showed
      better regulation of body temperature (Tb) and demonstrated considerably higher
      radiation from the neck. 4. The greater food intake of the naked neck chickens at
      15 degrees C was associated with significantly higher packed cell volume,
      haemoglobin concentration, heart and liver size. These appear to involve both
      higher heat production and haemodynamic changes to accommodate the higher oxygen
      demands of the naked neck chickens at low Ta. 5. The results indicate the ability
      of the naked neck chickens, on the one hand to thermoregulate at low Tas and, on
      the other their slightly better capacity to maintain Tb at high Tas. However, no
      genotype advantage was obtained under diurnal cyclic temperature conditions.

PMID- 9568312
TI  - Progressive bradycardia, a possible factor in the pathogenesis of ascites in fast
      growing broiler chickens raised at low altitude.
AB  - 1. The first objective was to evaluate baseline heart rate (HR) responses in fast
      growing broilers fed ad libitum from 1 to 45d or subjected to a food restriction
      (85%, 70% and 55% of ad libitum from 7 to 21d) and a refeeding (22 to 45d)
      regimen in a normal thermal environment. The second was to evaluate HR and
      haematocrit responses in fast growing broilers reared at a low environmental
      temperature and fed ad libitum (A-L) from 1 to 42d, subjected to food restriction
      (70% ad libitum) between 7 to 21d and refed thereafter (R-R), or subjected to
      food restriction between 7 to 42d (R), and to follow the changes in normal birds
      and those prone to ascites. 2. The baseline HR in the normal thermal environment
      at 21 and 45d in birds fed ad libitum was lower (P < 0.001) than at 7d. The food
      restricted groups had higher HRs at 21d than at 7d, with the differences
      significant (P < 0.01) for the 70% and 55% treatments. At 21d the HRs in
      restricted groups were significantly higher (P < 0.01) than in ad libitum-fed
      birds. After returning to ad libitum feeding the HRs in these birds tended to
      decline, with the differences significant (P < 0.05) for the 70% and 55%
      treatments. 3. In the birds exposed to cold, each feeding regimen produced
      distinct patterns of change in HR and haematocrit. Both feeding regimen and age
      had significant (P < 0.001) effects on the changes of both variables. Relative to
      7d, on 14d and 21d the HRs decreased and haematocrits increased in all groups,
      but the rates of change were highest in the A-L and R-R birds. The first
      fulminant cases of ascites were observed during the third week in the A-L group
      and during the fourth week in the R-R group. None of the chickens from the R
      group developed ascites. Altogether, the incidence of ascites was 48% in the A-L
      group and 28% in the R-R group. 4. Among the birds exposed to cold, the ascitic
      birds had significantly (P < 0.001) lower HRs and higher haematocrits than normal
      birds from the same feeding regimen group. The time trends in the rates of change
      in HR and haematocrit were distinctly different (P < 0.001) for ascitic and
      normal birds. The change in feeding regimen from restricted to ad libitum in the
      R-R group resulted in a significant (P < 0.001) decrease in HR and increase in
      haematocrit. 5. In view of the evidence presented, it appears that hypoxaemia and
      tissue hypoxia in broiler chickens may be a result of circulatory insufficiency
      associated with progressive bradycardia rather than, as commonly believed,
      pulmonary insufficiency. In this situation the pulmonary hypertension may be a
      secondary symptom.

PMID- 9568310
TI  - Effect of follicle-stimulating hormone on different cell sub-populations in the
      ovary of newly hatched chicks treated during embryonic development.
AB  - 1. Cell sub-populations of the ovary of newly-hatched chicks were assessed
      following follicle stimulating hormone (FSH) treatment during embryonic
      development. Changes in cell number and the amount of oestradiol in serum were
      determined. 2. White Leghorn chick embryos received 1 microgram FSH applied to
      the chorioallantoic membrane at 13, 15, and 17 d of incubation. Within 24 h after
      hatching, animals were killed and blood was collected. The left ovary was
      immediately removed then weighed and processed by an enzymatic-mechanical
      dissociation method for total cell count. An air-drying method was also used for
      meiotic preparations to study the germinal cells. 3. The pre-follicular ovary is
      able to respond to FSH by inducing an increase both in the serum oestradiol
      concentration and in the number of steroidogenic cells and of poorly
      differentiated cells of the ovarian medulla. 4. FSH increases the number of
      oogonia, which are responsible for a sharp increase in the total population of
      germ cells in the FSH-treated ovary. 5. It is possible that FSH acts to increase
      the proliferation of oogonia and a delay in the meiotic prophase through a change
      in the microenvironment rather than by a direct effect on germ cells.

PMID- 9568313
TI  - A model for the effect of constant photoperiods on the rate of sexual maturation
      in pullets.
AB  - 1. This paper reviews evidence from 15 experiments, reported over a span of 44
      years, in which pullets were reared from hatching to sexual maturity on 2 or more
      constant photoperiods. 2. The evidence strongly indicates that earliest age at
      first egg (AFE) was observed when pullets were held on constant 10 h days (though
      earlier maturity is easily induced by increasing the photoperiod during rearing).
      The pair of equations which best describe the relationship between AFE (y, d) and
      photoperiod (x, h) are for x < or = 10 h, y = 175.8-1.731x; for x > or = 10 h, y
      = 155.5 + 0.301x. 3. This 2-straight-line model, hinged at 10 h, should be used
      in preference to curvilinear models published earlier, which wrongly predict that
      pullets reared on long days (14 h to 17 h) mature faster than birds reared on
      constant 10 h.

PMID- 9568314
TI  - Changes in plasma alpha 1-acid glycoprotein concentration and selected immune
      response in broiler chickens injected with Escherichia coli lipopolysaccharide.
AB  - 1. Changes in plasma alpha 1-acid glycoprotein (AGP) concentration and immune
      responses following Escherichia coli lipopolysaccharide (LPS) injection were
      studied in broiler chickens. 2. Higher plasma AGP concentrations were observed
      from 12 to 48 h after a single injection of LPS. 3. The highest concentration of
      plasma AGP was observed on day 2 followed by a gradual decrease in chicks
      injected with 150 micrograms/kg body weight of LPS every day for 13 d. 4. Plasma
      AGP concentration in chicks injected daily with LPS at 900 micrograms/kg body
      weight for 13 d increased on day 2, and decreased on day 4 to the concentration
      found before the injection. The concentration increased again on day 10. 5.
      Changes in plasma interleukin-1 (IL-1) like activity were similar to those in
      plasma AGP concentration when LPS was injected daily at 900 micrograms/kg body
      weight for 3 d. 6. Responses of blood mononuclear cell (MNC) proliferation to
      mitogen or concanavalin A, (Con A), and pokeweed mitogen (PWM) were positively
      correlated with changes in plasma AGP concentration. 7. The results suggest that
      plasma AGP concentration could be used as a positive indicator of changes in
      blood MNC proliferation to a mitogen and in plasma IL-1 like activity.

PMID- 9568315
TI  - Effects of food and water withdrawal and high temperature exposure on diurnal
      variation in blood viscosity of broiler chickens.
AB  - 1. Three experiments were conducted to investigate the diurnal variation of blood
      viscosity in broilers. In experiment 1 food and water were supplied freely at 20
      degrees C (20-FW). In experiment 2 food and water were withdrawn at 20 degrees C
      (20-NFW), while in experiment 3 food and water were withdrawn at 30 degrees C (30
      NFW). 2. Blood sampling time points were 09.00 h, 15.00 h, 21.00 h, 03.00 h and
      09.00 h the next day in each experiment. 3. In all experiments, whole blood
      viscosity (WBV), red blood cell count (RBC) and haematocrit (HCT) were greater
      during the dark (21.00 h and 03.00 h) than during the light period. During the
      dark period, there were no differences in WBV, RBC and HCT between 20-FW and 20
      NFW, or between 20-NFW and 30-NFW. At 09.00 h, WBV and HCT were higher in 20-FW
      than in 20-NFW. At 15.00 h and 09.00 h (day 2), WBV and HCT were greater in 20
      NFW than in 30-NFW. 4. There were no light-dark differences in plasma viscosity
      (PV), plasma protein concentration (PPC) or mean corpuscular volume (MCV) in any
      experiment. However, 20-NFW birds had a lower PPC and higher MCV compared with 20
      FW, and a higher PPC and lower MCV compared with 30-NFW, while no difference was
      found in PV. 5. WBV increased linearly with RBC and HCT. PV increased with PPC,
      while MCV decreased. 6. These results indicate that there is diurnal variation in
      whole blood viscosity, which is greater during the dark than during the light
      period. During the light period it is strongly influenced by high environmental
      temperature and food and water withdrawal.

PMID- 9568316
TI  - Heart rate in developing ostrich embryos.

PMID- 9568317
TI  - Notes on the contribution of wars and conflicts to medical achievements.

PMID- 9568318
TI  - Retroviral gene transfer into porcine keratinocytes following improved methods of
      cultivation.
AB  - We embarked on a program examining the application of cultured epithelial sheets
      to skin wounds in pigs using retroviral gene transfer as a means to follow the
      grafted cells. In the past similar studies have been hampered by an inability to
      grow porcine keratinocytes without seeding at an extremely high density. In this
      study we found that excellent results could be achieved with Opti-MEM-1 (Gibco
      BRL Life Technologies) containing 1 per cent foetal calf serum, 0.5 mM Ca2+ and
      no other growth factors or stimulants. Keratinocytes were plated on gamma
      irradiated 3T3 feeders on surfaces which had previously been coated with rat tail
      collagen I. Keratinocyte cultures were established at a seeding density of 5 x
      10(4) cm-2. The yield of cells from 1 cm2 of skin was sufficient to set up a 75
      cm2 flask. Cultures reached 80-90 per cent confluence in 7-10 days, after which
      they were passaged 1:3 multiple times, taking 3-4 days to reach the same
      confluency. Allowing cultures to remain confluent for 1 week was sufficient to
      allow Dispase removal of an intact sheet. Using these techniques porcine
      keratinocytes were transduced at an average frequency of 25.3 per cent (+/- 14.0
      SEM) with the retroviral vector MFG lacZ nls by growth on the gamma-irradiated
      retroviral producer line GP + envAm12.

PMID- 9568319
TI  - Oxidative damage to protein and alterations to antioxidant levels in human
      cutaneous thermal injury.
AB  - Evidence that oxygen free radicals may be contributory to further tissue damage
      in the events following cutaneous thermal injury supports a role for
      interventional therapy using antioxidants. However, previous work has relied
      almost entirely on animal-based models with little clinical information
      available. Also, methods used to support an oxidative role in thermal injury have
      relied almost exclusively upon the use of lipid peroxidation studies. Further
      work substantiating a contributory role of free radicals is therefore required
      using additional methodology before considering antioxidant therapy aimed at
      retarding tissue damage. We investigated general oxidative damage to protein in
      burn blister fluid by quantifying the protein carbonyl levels from 11 patients
      admitted with superficial or partial thickness burns. Total antioxidant capacity
      was also assessed, together with measurement of protein and the antioxidants uric
      acid and bilirubin. Data were compared with values obtained for serum in healthy
      volunteers. Following thermal injury, burn blister fluid protein carbonyl level
      was increased by almost 50 per cent (P = 0.005) compared with normal serum.
      Antioxidant scavenging capacity, protein and bilirubin were all significantly
      reduced, but uric acid unaltered compared with control values. The present data
      support a role for oxidative damage in cutaneous thermal injury.

PMID- 9568320
TI  - Effects of N-acetylcysteine on lung glutathione levels in rats after burn injury.
AB  - This study was designed to determine the effect of N-acetyl-cysteine (NAC, a
      natural hydroxyl radical scavenger) treatment on levels of pulmonary
      malondialdehyde (MDA, the end product of lipid peroxidation) and glutathione
      (GSH, a natural antioxidant) in thermally injured rats. Severe skin scald injury
      (30 percent TBSA) caused a significant decrease in GSH levels, and a significant
      increase in MDA levels in lung tissue both at 1 h and 1 day postburn injury.
      Treatment of rats with NAC (15 mg/kg intraperitoneally, 15 min and 12 h following
      the burn) significantly improved GSH levels, and decreased ongoing lipid
      peroxidation at 1 day. This study showed that thermal injury resulted in
      increased pulmonary lipid peroxidation, and this remote organ injury was
      decreased by treatment with NAC. In addition NAC, a scavenger of hydroxyl
      radicals, improved GSH levels in the lungs. The higher level of GSH in the lungs
      of the burned rats treated with NAC could be due to either a decrease in the rate
      of degradation of GSH or to an increase in its synthesis. No data about these
      possibilities are provided.

PMID- 9568321
TI  - Post-traumatic stress, pain and anxiety in adult burn victims.
AB  - This article describes the relationship between post-traumatic morbidity, anxious
      anticipation of pain and pain perception in 33 adult burn patients. Burn patients
      were assessed, on average, 7 days after admission to the hospital. Five times a
      day nurses asked the patients to provide pain ratings. The more patients suffered
      from post-traumatic stress, the more their anxiety state was elevated. The
      association between post-traumatic stress and pain perception was, controlling
      for the effects of anxious anticipation, spurious.

PMID- 9568322
TI  - An investigation of the prevalence of psychological morbidity in burn-injured
      patients.
AB  - Research on the psychological impact of burn injuries has concentrated on major
      burns, while small burns have been largely neglected. In a prospective study, 45
      patients with burn injuries ranging from 1 per cent or less up to 40 per cent
      total body surface area were assessed using semi-structured interviews within 2
      weeks of sustaining the burn, and followed-up at approximately 3 months postburn
      to investigate the prevalence of mental health problems. The prevalence of
      clinically significant levels of anxiety, intrusions and avoidance remained
      similar at 2 weeks and 3 months postburn, however, the prevalence of depression
      and Post Traumatic Stress Disorder (PTSD) increased 6- and 4-times, respectively,
      by 3 months. Patients with small burn injuries of 1 per cent or less also
      experienced clinically significant levels of psychological difficulties postburn.
      The implications for the identification of patients at risk of future
      psychological morbidity are discussed.

PMID- 9568323
TI  - Changes in levels of serum IL-8 in burned patients.
AB  - Interleukin (i.l.)-8 levels in serial serum samples of 10 burned patients were
      analysed. The total body surface areas (TBSAs) of the burn injury ranged 30 to 85
      per cent. Of these ten patients, five recovered and the other five, who were
      septic, died. On admission at about 5-13 h postburn, one of the five survivors
      and two of the non-survivors had serum IL-8 levels higher than 18.1 pg/ml, which
      is the detection limit of the IL-8 assay kit. The serum IL-8 values of six
      healthy laboratory personnel included in the present study were all less than
      18.1 pg/ml. Afterwards, an initial peak serum IL-8 response was detected within 2
      4.5 days postburn. Significant differences in the peak serum IL-8 levels were not
      found between patients with TBSAs of greater or less than 50 per cent and
      patients who survived or expired from burn injury. In the survivors, serum IL-8
      remained low, whereas IL-8 increased markedly, starting at about one week
      postburn in four of the five non-survivors with confirmed sepsis. Significant
      differences in the maximum serum IL-8 levels were detected between patients who
      recovered vs. those who died from the thermal injury. In conclusion, the results
      showed that there was an increase in serum IL-8 postburn. Serum IL-8 was
      significantly higher in the septic patients, who all died. This cytokine may play
      a significant role in the pathophysiology of sepsis in burned patients.

PMID- 9568324
TI  - Serum enzymatic changes modulated using trypsin: chymotrypsin preparation during
      burn wounds in humans.
AB  - The levels of marker enzymes for liver function, namely transaminases (SGPT,
      SGOT), creatine phosphokinase (CPK), alkaline phosphatase (ALP) and lactate
      dehydrogenase (LDH) were estimated in the sera of burn patients by administering
      trypsin: chymotrypsin preparation and comparing with an untreated group.
      Neutrophil proteolytic activity was also measured by assaying the lysosomal
      enzymes, namely neutrophil elastase and cathepsin D. Our earlier studies have
      already proved the efficacy of the above enzyme preparation to burn patients on
      the enhancement of vascular responses during the acute phase of the burn injury.
      These beneficial responses were brought about by the modulation of acute phase
      proteins expressed in the liver. Hence, it is of interest to study the changes in
      the above mentioned liver enzymes and certain lysosomal enzymes in the serum
      during the first 10 days of burn injury. The levels of liver and lysosomal
      enzymes markedly decreased in the treated group when compared with the untreated
      group. The enzyme studies clearly indicated that the initial rise in the liver
      enzymes was minimized in the treated group when compared with the untreated group
      and this helped in reducing the stress to the liver in the treated cases. The
      increase in the activity of alpha 1-antitrypsin and alpha 2-macroglobulin and
      decreased levels of C-reactive protein are attributed to the reduction of
      proteolytic enzyme levels in the treated group and minimizing the degradative
      changes during wound repair.

PMID- 9568326
TI  - Electrocution due to contact of industrial equipment with power lines.
AB  - Electrocution due to contact of construction equipment with power lines is not
      uncommon as a source of industrial injury. We report seven such cases. Two
      patients sustained cardiac arrest and were successfully resuscitated at the
      scene. Four patients lost consciousness and in two cases, amnesia for the event
      was encountered. No long-term cardiac or neurologic effects were noted. Surgery
      including amputation was sometimes required. In all cases, the patient was on the
      ground touching the machinery or touching cables connected to the machinery at
      the time of injury. The importance of exercising due care in industrial safety
      measures is stressed. Prompt CPR was life saving in two cases.

PMID- 9568325
TI  - Characterization of T-cell subsets infiltrating post-burn hypertrophic scar
      tissues.
AB  - In this study, skin-infiltrating cells were characterized in both the active and
      remission phases of post-burn hypertrophic scar biopsies. Immunohistochemistry
      examination of active phase samples showed an abundant presence of Langerhans
      cells, T cells, macrophages, a low presence of natural killer cells and the lack
      of B lymphocytes. In active hypertrophic scars T lymphocytes infiltrate deep into
      the superficial dermis and are also observed in the epidermis: CD3+ cells were
      present at about 222 +/- 107 per 0.25 mm2. In particular the analysis of
      lymphocyte subpopulations showed that CD4+ T cells predominate in the dermis as
      well as in the epidermis of active hypertrophic scars whereas CD8+ cells were
      less well represented (CD4/CD8 ratio is 2.06). This distribution was also shown
      in remission phase samples and in normotrophic scar specimens, although the
      lymphocyte number was significantly lower. Approximately 70 per cent of T
      lymphocytes present in the tissue involved in active phase hypertrophic scar
      samples were activated (positive with anti-HLA-DR and IL-2 receptor antibodies)
      which is significantly higher than remission phase hypertrophic and normotrophic
      scars, in which positivity was 40 and 38 per cent, respectively. Upon activation,
      the lesional lymphocytes release several cytokines, locally and transiently, that
      interact with specific receptors in response to different stimulation. Central to
      the immune hypothesis of hypertrophic scars is that some of the T-cell
      lymphokines act on keratinocytes, fibroblasts and other cell types to induce
      changes characteristic of these scars. The presence and close proximity of
      activated T lymphocytes and antigen-presenting cells of various phenotypes in
      both the epidermis and dermis of hypertrophic tissues provides strong
      circumstantial evidence of a local immune response. However, the manner in which
      T cells achieve and maintain their activated state in hypertrophic tissues is not
      yet known, and both antigen-dependent and independent mechanisms may contribute.

PMID- 9568327
TI  - Electrical injury and the frequency of cardiac complications.
AB  - A retrospective review of the patients with electrical injuries admitted over a 5
      year period was performed to establish the frequency of cardiac complications.
      There were 145 admissions during this time. A total of 128 (88 per cent) were low
      voltage injuries and 17 (12 per cent) were high voltage (> 1000 V) injuries. Of
      the 145 admissions, 104 (72 per cent) had a 12-lead electrocardiogram (ECG)
      recorded within 24 h of their injury. Of these patients, 73 (75 per cent) were
      then observed on a cardiac monitor for at least 24 h post-injury. Cardiac
      abnormalities were noted in four patients (3 per cent) during this period. Three
      patients had occasional ectopic beats which settled spontaneously over a 24 h
      period post-injury. The fourth patient developed atrial fibrillation (AF) after a
      high voltage injury which resolved following intravenous digoxin. Cardiac
      complications were more frequent in those who had experienced a loss of
      consciousness at the time of injury and in those who suffered a high voltage
      electrical injury. All of the patients with cardiac complications had these at
      the time of admission to hospital. This suggests that if there is no history of a
      loss of consciousness and the 12-lead ECG recorded on attendance at the hospital
      is normal, it is unlikely that the patient will go on to develop cardiac
      problems.

PMID- 9568328
TI  - Peripheral neuropathy in burn patients.
AB  - Neuropathy in burn patients is frequently overlooked. This study aimed at looking
      for neuropathies among burn patients. It included 55 burn patients, whether
      symptomatic or asymptomatic, with variable depths of burn at different stages.
      Their ages ranged from 8 to 55 years with a mean age of 23.6 +/- 11.1 years. All
      patients were submitted to clinical examination, electromyographic and motor
      conduction velocities of burned and unburned limbs. Serum electrolyte, blood urea
      and creatinine were measured for all patients. Sixteen patients (29 per cent) had
      peripheral neuropathy. Only six had symptoms and signs of peripheral neuropathy.
      The most frequently diagnosed neuropathy in this study was mononeuritis multiplex
      in nine patients (56 per cent), then generalized distal axonal neuropathy in five
      patients (31 per cent) and entrapment neuropathy in two patients (13 per cent).
      In patients with mononeuritis, 29 nerves were affected, 24 nerves related to the
      site of the burn and five nerves were away from the site of the burn. All the
      entrapment neuropathy developed after wound healing. Age above 20 years, electric
      burns burns involving full thickness of the skin and a surface area of more than
      20 per cent were associated with a significantly higher prevalence of neuropathy.
      Other parameters were not found to be significant in the development of
      neuropathy.

PMID- 9568330
TI  - Blood platelets in severely injured burned patients.
AB  - Unbelievable decrease of blood-platelet in the severely burned patients during
      the treatment of skingrafting caused two patients to unexpected death. From the
      records of changes of platelet number, a certain 'platelet curve' was made. By
      observing the curve, our treatments of skingrafting were carried out during the
      stable period and from then on we had no death cases.

PMID- 9568329
TI  - The last 10 years in a burn centre in Ankara, Turkey: an analysis of 5264 cases.
AB  - This is a retrospective study analysing 5264 patients treated in the burn centre
      at Gulhane Military Medical Academy from 1 January 1986 to 31 December 1995. Our
      burn centre is not only the first, but one of the best established and supported
      in Turkey. Our present study has the largest patient group of other previously
      published studies from Turkey. Of the total patients studied, 4464 patients had
      minor burns and were treated on an outpatient basis and 800 patients had moderate
      to major burns. Although our centre is in a military area in Ankara, only 1047
      (20 per cent) patients were military personnel and the military-related burn
      causes comprised only 6 per cent of the total. The remaining 4217 (80 per cent of
      the total patients) were civilians. Flame injuries were also more frequent in
      military patients than civilians. Minor burns were most common in the age group 0
      10 years old (40 per cent) and moderate to major burns in the age group 21-30
      years (54 per cent). Scalds were the main cause of paediatric burns. Male
      patients were dominant. The overall mortality among inpatients was 18.2 per cent
      and mean total body surface area (TBSA) was 57.6 per cent in patients who died.
      134 patients demonstrated inhalation injury and 82 per cent of these patients
      died. The epidemiological pattern of our patients is similar to that in other
      studies from developed countries, although some ethnic causative factors could be
      found. Our study indicates that emergency measures should be taken to prevent
      flame injuries at military barracks and industrial workplaces and scalding
      accidents to children at home and throughout the country.

PMID- 9568332
TI  - Opsite spray: its use for fixation of meshed skin grafts. Simple and low tech.
AB  - The fixation of skin grafts often poses a problem, particularly in patients who
      have undergone tangential excision and grafting for burns. Sutures, staples,
      fibrin glue and other adhesives have been used for graft fixation. We present the
      use of Opsite spray as a simple method for graft fixation and stabilization.
      Opsite markedly reduced pain and discomfort at the time of first graft dressing
      and obviated the necessity for an anaesthetic which is often required for the
      removal of staples.

PMID- 9568331
TI  - Burns during pregnancy: a gloomy outcome.
AB  - The effect of burns on fetal and maternal survival is known to be detrimental.
      This prospective study describes the performance of pregnant burned patients who
      were managed and followed up for fetal and maternal outcomes at Ain Shams
      University's burn unit and Maternity Hospital during the period from October 1995
      to September 1996. During the 12-month period, 27 pregnant burned patients were
      managed. Fetal and maternal mortality correlated with the total body surface area
      (TBSA) burned, the mortality rate being 63 per cent for both mothers and fetuses
      in the 25-50 per cent TBSA group. A fetal loss of 56 per cent with no maternal
      loss were recorded in the 15-25 per cent TBSA group. Experience in dealing with
      pregnant burned patients proves that early surgical excision and skin grafting,
      with timely termination of pregnancy are the best lines of treatment. Prevention
      or minimizing the effects of the burns may be achieved by proper education and
      guidance of the pregnant woman.

PMID- 9568333
TI  - Micrografting in the treatment of severely burned patients.
AB  - The micrografting technique, employed to treat patients with extensive TBSA burns
      and reduced areas of healthy donor skin, was assessed simultaneously with
      traditional mesh grafts (STSG) or Tiersch grafts in the treatment five severely
      burned subjects (average TBSA burned 35.6 per cent; average per cent of full
      thickness wounds 32.6 per cent). At the first clinical control on day 6 post
      surgery, 93 per cent of the micrografted area was in situ and health;
      epithelialization of the wound sites was complete at day 21. Meshed STSG yielded
      90 per cent attachment at day 6 post-surgery, with epithelialization complete at
      12 +/- 2 days post-surgery. Functional results were equivalent no matter what
      technique was used, while aesthetic results were better in the areas where
      micrografting was carried out. Although the micrograft technique is labour
      intensive, if the expansion needed is at least 1:6, the aesthetic and functional
      results obtained are comparable to, or better than, those with meshed grafts.
      Also, large segments of micrograft are not compromised if a small area of mesh
      becomes detached, and epithelialization is faster and more uniform, enabling a
      reduction in both infection and length of hospital stay.

PMID- 9568334
TI  - Cryopreserved cadaveric allografts for treatment of unexcised partial thickness
      flame burns: clinical experience with 12 patients.
AB  - Partial thickness burns (PTB) usually heal within 3 weeks. Prevention of
      infection and desiccation of the wounds are crucial for optimal healing. Early
      tangential excision of the burn eschar and allografting prevent deepening of the
      burns, and are therefore advocated for treatment with the best functional and
      aesthetic results. For superficial partial thickness burns (SPTB) conservative
      use of topical antimicrobial agents with frequent dressing changes are
      implemented. We compared the conservative treatment for PTBs and SPTBs to
      grafting cryopreserved cadaveric allografts with no prior excision. Twelve
      patients with flame PTB areas were allografted after mechanical debridement
      without excision of the burn wounds. The allografts were cadaveric skin
      cryopreserved by programmed freezing and stored at -180 degrees C for 30-48
      months. Matching burns for depth and area were treated with silver sulfadiazine
      (SSD) one to two times daily until healing or debridement and grafting were
      required. It was found that 80 per cent of the cryopreserved allografts adhered
      well and 76 per cent of the treated areas healed within 21 days, whereas only 40
      per cent of the SSD-treated burns healed within 21 days. Partial thickness burns
      can be treated successfully with viable human allografts (cryopreserved cadaveric
      skin) with no prior surgical excision. The burn wounds heal well within 3 weeks.
      For deep partial thickness burns (DPTB) treatment with allografts has no
      advantage if they have not been previously excised.

PMID- 9568335
TI  - The use of an 'adhesive contact medium' (Hypafix) for split skin graft fixation:
      a 12-year review.
AB  - Since the introduction in 1985 of the technique of graft fixation with Hypafix,
      the method has been adapted for use in burns of all sites and extent, and has
      proven to be effective in over 500 burn patients. The technique is versatile,
      safe, simple, reliable and inexpensive. More importantly, there is a significant
      improvement in cosmesis due to the earlier introduction of an 'Adhesive Contact
      Media', the blending of the graft at the edges, and the lack of skin bridges and
      shoulders. It has become an integral part of burn management at the Women's and
      Children's Hospital Burn Unit. Current scar management is based on the principles
      of: Excision of deep dermal burns about Day 7. Graft fixation with Hypafix.
      Continuing use of appropriate 'contact media'. Continuing close supervision in a
      designated Burn Scar Clinic.

PMID- 9568336
TI  - The role of pre-expanded free flaps in revision of burn scarring.
AB  - The authors present two patients affected by scars resulting from burning of over
      60 per cent of the total body area, in which the pre-expansion of a free flap has
      been used to increase the tissue surface useful for transfer from the only area
      of residual healthy skin (left forearm, left parascapular region). In both cases
      it was possible to transfer abundant healthy tissue into the desired areas,
      obtaining a rapid release of the region, which made possible an early physical
      rehabilitation of the patient starting after the second postoperative week. One
      of the main problems encountered, when facing surgical rehabilitation for the
      seriously burned patient, is the poor availability of skin donor areas suitable
      for reconstructive flaps. The pre-expansion of free flaps provides an advantage
      in that it allows the few integral residual areas to be used, improving
      vascularization and therefore increasing the available surface. Furthermore, as
      pre-expansion reduces tension on the margins, it allows for the easier closing of
      the donor area, with a minor risk of complications and a better scar outcome.

PMID- 9568337
TI  - Povidone iodine plus neosporin in superficial burns--a continuing study.
AB  - A total of 1053 patients with superficial burn injury were treated with povidone
      iodine plus neosporin (PVP + N) and the results after treatment were compared
      with those obtained after treating 1089 patients with silver sulphadiazine (SSD).
      Qualitative analysis showed Staphylococcus aureus and Pseudomonas spp. to be the
      most common infecting organisms. Quantitatively, fewer patients showed infection
      on the 7th and 18th day post-treatment in the PVP + N group (P < 0.01 and P <
      0.001, respectively). Similarly, healing times were also better with PVP + N,
      with a maximum number of patients having healed within 15 days (P < 0.001).
      However, the mortality rates were not much different between the two groups.

PMID- 9568338
TI  - Boiling wax burn in mid-autumn festival in Hong Kong.
AB  - An unusual cause of burn, contact with boiling wax by children and adolescents
      during the annual mid-autumn festival in Hong Kong is presented. 57 patients who
      suffered from hot wax burn over the period 1986-1996 were admitted to the Burns
      Unit of the Prince of Wales Hospital. This special burn should be preventable by
      public education.

PMID- 9568339
TI  - Atypical post burn oedema presenting with obstruction of veins at the thoracic
      inlet.

PMID- 9568340
TI  - Skin injuries afflicting three oil workers following contact with calcium bromide
      and/or calcium chloride.
AB  - Calcium bromide brine is a highly concentrated aqueous solution of calcium
      bromide and calcium chloride. It is used extensively in the oil industry. This
      solution and its components are recognized as causes of skin injury and
      information is available from the manufacturers on their safe use and handling.
      Two patients who were injured following unprotected skin exposure to this
      solution and one patient who was injured following exposure to calcium chloride
      powder are reported. All sustained skin injuries characterised by an absence of
      pain and a delayed clinical appearance of the full extent of the injury.
      Furthermore healing was complicated by graft loss or was slow. Although organic
      bromine compounds are recognized as a cause of skin injuries, no previous reports
      of such injuries to humans secondary to calcium chloride or bromide exposure were
      found in the medical literature. Our experience with these patients is described.

PMID- 9568341
TI  - Liquid nitrogen injury: a case report.
AB  - Despite the widespread use of liquid nitrogen, there are few reports of injuries
      caused by the use of this substance. We report a case in which a severe liquid
      nitrogen burn, requiring digital amputation, occurred despite the wearing of
      protective gloves. This case illustrates the potential dangers of working with
      liquid nitrogen, and raises questions as to whether adequate precautions are
      being taken to prevent such injuries.

PMID- 9568343
TI  - Use of cyanoacrylate glue to prepare cultured keratinocyte sheets for grafting.
AB  - We describe a method to prepare keratinocyte cultured sheets for grafting based
      on the use of an organic glue (n-butyl-2-cyanoacrylate). It is a rapid and easy
      method in which the cultured layers of keratinocytes remain with a surface area
      similar to the original cultures.

PMID- 9568342
TI  - A role for lasers in the treatment of pigmented skin grafts.
AB  - The development of aberrant pigmentation represents an unwelcome complication to
      an otherwise successful split skin graft resulting in a loss of colour match and,
      so it follows, of cosmesis. We present two cases where lasers have been
      successful in the treatment of this problem.

PMID- 9568344
TI  - Recent references.

PMID- 9568346
TI  - The diagnostic value of oesophageal radionuclide transit in patients admitted for
      but without acute myocardial infarction.
AB  - The use of radionuclide transit (RT) as a screening test for chest pain of
      oesophageal origin has been debated. The aim of this study was to determine the
      value of RT as a screening test for oesophageal disorders in comparison with
      oesophageal manometry in patients admitted with acute chest pain but without
      acute myocardial infarction (non-AMI patients), and to assess the frequency of
      oesophageal disease present in these patients. A total of 222 non-AMI patients
      entered the study. An extensive examination programme comprised noninvasive
      cardiac studies, pulmonary studies, a careful physical examination of the
      musculoskeletal system, and oesophago-gastric examinations including endoscopy,
      pH monitoring of the oesophagus and a Bernstein test. In 91% of the patients one
      or more diagnoses were obtained. Based on clinical and laboratory data a
      'consensus' diagnosis was made. With manometry as the reference RT had a poor
      sensitivity (35%) but an acceptable specificity (82%). With the consensus
      diagnosis as the gold standard the sensitivities of both manometry and RT were
      poor (29%), whereas the specificity of RT, but not of manometry, was very high
      (97%). Gastrointestinal diagnoses were found in 57% of the patients. In
      conclusion, none of the applied oesophageal examinations are valuable as single
      screening tests. Both RT and manometry have low sensitivities. RT may be used as
      a cheap, noninvasive and rapid supplementary examination. When positive, it
      strongly supports further invasive studies of the oesophagus in non-AMI patients
      with unexplained chest pain.

PMID- 9568345
TI  - Methodological aspects of the evaluation of endothelium-dependent vasodilatation
      in the human forearm.
AB  - The present study, involving 56 healthy subjects from a health screening, was
      undertaken to address some methodological questions regarding the measurement of
      endothelial function using local intra-arterial infusions of metacholine (2 and 5
      micrograms min-1) to evaluate endothelium-dependent vasodilatation, and sodium
      nitroprusside (SNP, 5 and 10 micrograms min-1) to evaluate endothelium
      independent vasodilatation. Forearm blood flow (FBF) was measured by venous
      occlusion plethysmography. The ratio of FBF during the highest dose of
      metacholine to FBF during the highest dose of SNP was used as an index of
      endothelial function. In 10 young volunteers the procedure was repeated after 2 h
      and again after 3 weeks in order to study short-term and long-term
      reproducibility of the method. Neither the vasodilatatory response to metacholine
      (r = 0.006) nor that to SNP (r = 0.08) was related to resting FBF. Neither the
      circumference nor the length of the arm was related to endothelial function (r =
      0.01-0.11), as evaluated by the FBF on metacholine to nitroprusside ratio (mean
      1.3 +/- 0.3 SD). The use of a wrist cuff to exclude hand circulation, or not, did
      not influence the evaluation of endothelial function significantly. Maximal FBF
      after 3 min of arterial occlusion of the forearm was significantly related to
      blood flow during both metacholine (r = 0.53, P < 0.01) and nitroprusside
      infusion (r = 0.36, P < 0.05), but not to the FBF on metacholine to nitroprusside
      ratio (r = 0.01). The short-term and long-term reproducibility of FBF during
      vasodilatation with metacholine and SNP was good (r = 0.89-0.97, P < 0.001),
      while the individual measurements for resting FBF were less reproducible when
      repeated after 3 weeks (r = 0.34). In conclusion, endothelial function was not
      related to resting FBF, nor to the arm circumference or length. No major
      difference was seen whether endothelial function was evaluated with or without
      exclusion of the hand circulation. Maximal FBF during reactive hyperaemia was not
      related to endothelial function.

PMID- 9568347
TI  - Myocardial perfusion scintigraphy (SPECT) during adenosine stress can be
      performed safely early on after thrombolytic therapy in acute myocardial
      infarction.
AB  - The objective of this study was to evaluate the safety of myocardial perfusion
      scintigraphy with Tc-99 m sestamibi during adenosine stress in patients with
      recent thrombolytically treated myocardial infarction. Eighty-four patients with
      thrombolytically treated myocardial infarction, 59 males and 25 females, aged
      62.9 +/- 8.4, were eligible for myocardial perfusion scintigraphy during
      adenosine provocation. Exclusion criteria for adenosine stress were hypotension,
      unstable angina pectoris, cardiac failure, pericarditis and atrioventricular
      block (AV block) II-III. Adenosine-stress and resting myocardial perfusion
      scintigraphy was performed 2-5 days after thrombolysis. Scintigraphy at rest was
      done 24 h after the stress study. Sixty patients (71%) experienced some kind of
      side-effects during adenosine infusion. The most frequent side-effects were
      dyspnoea in 43/84 patients (51%) and unspecific chest discomfort in 26/84
      patients (31%). During infusion, ST depressions or elevations on ECG were seen in
      9 patients (11%), 5 of whom experienced atypical chest discomfort. Five patients
      (6%) described typical angina but none of them showed electrographic signs of
      myocardial ischaemia during infusion. Six patients (7%) developed transient AV
      block I-II. Reversible scintigraphic perfusion defects were seen in 67 patients
      (79%). No serious complications, such as death, reinfarction or severe
      arrhythmias, occurred during adenosine infusion or during a 3-day clinical follow
      up period. In conclusion, MIBI-SPECT during adenosine stress is a safe diagnostic
      method that can be performed in most patients early on after thrombolytically
      treated acute myocardial infarction. Side-effects are common but benign, and not
      different from those seen in patients with chronic coronary artery disease.

PMID- 9568348
TI  - Finger skin blood flow in response to indirect cooling in normal subjects and in
      patients before and after sympathectomy.
AB  - Finger skin blood flow was measured in 80 healthy subjects, using laser Doppler
      imaging during basal vasodilatation at a local temperature of 40 degrees C. The
      response to cooling of the contralateral hand at 15 degrees C was studied. A
      vasoconstriction index was calculated in all subjects and a nomogram was
      constructed, taking age into consideration. Compared with these normal subjects,
      four patients operated on with transthoracic endoscopic sympathectomy due to hand
      hyperhidrosis showed clearly attenuated responses. The results indicate that the
      test can be used to assess disturbances in the sympathetic regulation of the
      peripheral blood flow.

PMID- 9568349
TI  - Arterial and venous plasma catecholamines during submaximal steady-state
      exercise.
AB  - Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of
      maximal oxygen uptake were examined 11 times during exercise and recovery in nine
      young men. Intra-arterial blood pressure, heart rate and oxygen uptake were
      recorded continuously. All variables increased significantly during the initial 4
      min, after which oxygen uptake, diastolic blood pressure and arterial plasma
      adrenaline showed no further increase. Heart rate and plasma noradrenaline,
      however, continued to increase, although significantly more slowly, and were
      closely correlated (r = 0.81, 95% CI 0.71-0.87), as were systolic blood pressure
      and heart rate (r = 0.78, 95% CI 0.71-0.87). Venous plasma adrenaline showed a
      steady increase during the whole exercise period and thus a different response
      pattern from arterial plasma adrenaline. In conclusion, arterial plasma
      catecholamines respond to steady-state exercise by a two-phase pattern
      paralleling the changes in arterial blood pressure and heart rate. Venous
      sampling does not reveal this association.

PMID- 9568350
TI  - Compression-induced pulsatile blood flow changes in human legs.
AB  - Initial and sustained (7-h) impacts of foot-to-knee compression bandaging on leg
      arterial pulsatile blood flow were assessed by nuclear magnetic resonance
      flowmetry in eight healthy supine subjects. A widely used bandaging method (zinc
      impregnated gauze + Coban) and a slight variant (Coban only) were applied one
      week apart to one leg. Blood flow was measured on each day of bandage application
      before and after bandaging and after 7 h of normal activity. Initial mean sub
      bandage pressures (lateral gaiter) were between 28.4 and 28.9 mmHg but were
      significantly reduced after 7 h to 16.3-19.4 mmHg. Overall below-knee pulsatile
      blood perfusion was initially significantly increased by both methods mainly due
      to increased proximal blood flow. Bandaging was also associated with a decrease
      in blood perfusion of the nonbandaged control leg mainly due to a decrease in
      distal blood flow. Neither of these effects were sustained after 7 h. The fact
      that neither sub-bandage pressure nor blood flow was sustained may indicate a
      causal linkage, a concept consistent with the finding of a linear relationship
      between afternoon blood flow and sub-bandage pressure reductions. The
      implications of the present findings for venous ulcer therapy are speculative and
      based on the concept that arterial pulsatile flow augmentation is a positive
      feature. If so, more frequent bandage changes to provide transient flow
      stimulation or use of bandages to better maintain sub-bandage pressure to sustain
      flow increases may be useful.

PMID- 9568351
TI  - Cholinergic blockade and the mesenteric artery response to head-up tilt-induced
      central hypovolaemia.
AB  - The influence of muscarinic blockade on the superior mesenteric artery (SMA)
      response to head-up tilt (HUT) was assessed by Doppler ultrasound in eight
      healthy adults pretreated with i.v. glycopyrron. During supine rest, cholinergic
      blockade increased heart rate from 58 +/- 3 to 106 +/- 6 beats min-1 (mean +/-
      SE) and mean arterial pressure from 81 +/- 3 to 97 +/- 4 mmHg (P < 0.01) and it
      reduced the cardiac stroke volume from 89 +/- 6 to 59 +/- 7 ml (P < 0.01) with no
      significant effect on the SMA diameter and blood flow velocities. HUT provoked a
      further increase in heart rate to 134 +/- 5 beats min-1 (P < 0.01) and a
      reduction in stroke volume to 45 +/- 4 ml (P < 0.01). The early diastolic
      velocity increased from -51 +/- 4 to 6 +/- 8 cm s-1 during the normotensive stage
      of HUT and further to 21 +/- 9 cm s-1 during the hypotensive stage with a
      reduction in mean arterial pressure from 97 +/- 4 to 73 +/- 7 mmHg (P < 0.01)
      but, in contrast to control HUT (without cholinergic blockade), the end-diastolic
      velocity did not change significantly. Maintenance of blood velocity and diameter
      in spite of an increase in arterial pressure at rest indicates increased SMA
      impedance. Likewise, during hypovolaemia, a glycopyrron-induced inhibition in
      diastolic velocity supports an increase in SMA impedance. The results indicate
      cholinergic vasorelaxing influence on the superior mesenteric artery both at rest
      and during normotensive central hypovolaemia.

PMID- 9568352
TI  - Pulmonary venous blood flow pattern in patients with univentricular hearts
      following total cavo-pulmonary connection.
AB  - The objective of the study was evaluation of the pulmonary venous blood flow
      (PVF) pattern and the influence of ventricular function and atrioventricular
      valve regurgitation on this flow in patients with univentricular hearts post
      total cavo-pulmonary connection (TCPC). Transthoracic or transoesophageal
      echocardiographic studies were performed in 24 children with normal hearts (group
      A) and in 24 patients with univentricular hearts (group B). Ventricular function
      and atrioventricular valve regurgitation was semiquantitatively assessed.
      Systolic/diastolic maximal velocities and velocity time integrals (VTI) were
      measured from PVF tracings. Ejection fraction was measured by radionuclide
      angiography in 11 patients. Twelve patients underwent heart catheterization and
      angiography. In group B the PVF showed a biphasic flow velocity curve. The
      systolic integrals were smaller and the diastolic integrals were larger than in
      group A (6.4 vs. 13.0 cm, P = 0.0001, and 13.9 vs. 10.0 cm, P = 0.005). The
      pulmonary venous systolic flow fraction in 13 patients with an open fenestration
      and/or atrioventricular valve regurgitation grade 2-3 was significantly lower
      than in those 11 patients without fenestration and none/small regurgitation (0.19
      vs. 0.40, P = 0.05). In conclusion, the PVF pattern in children with
      univentricular hearts pallitated with TCPC is similar to the PVF pattern found in
      individuals with biventricular hearts showing a biphasic flow velocity curve
      despite the absence of pulsatile pulmonary artery flow. The PVF in patients with
      TCPC-palliated univentricular hearts is influenced by atrioventricular valve
      regurgitation and fenestration flow.

PMID- 9568353
TI  - Intelligent computer reporting 'lack of experience': a confidence measure for
      decision support systems.
AB  - The purpose of this study was to explore the feasibility of developing artificial
      neural networks that are able to provide confidence measures for their diagnostic
      advice. Computer-aided decision making can improve physician performance, but
      many physicians hesitate to use these 'black boxes'. If we are to rely upon
      decision support systems for such tasks as medical diagnosis it is essential that
      the computers indicate when the advice given is based on experience, i.e. give a
      confidence measure. An artificial neural network was trained to diagnose healed
      anterior myocardial infarction and to indicate 'lack of experience' when test
      electrocardiograms were different from the electrocardiograms of the training
      set. A database of 1249 electrocardiograms from patients who had undergone
      cardiac catheterization was used to train and test the neural network.
      Thereafter, the ability of the network to indicate 'lack of experience' was
      assessed using 100 left bundle branch block electrocardiograms, an
      electrocardiographic pattern that was excluded from the training set. The network
      indicated that 83% of the left bundle branch block electrocardiograms and 1% of
      the test electrocardiograms from catheterized patients were different from the
      electrocardiograms of the training set. All but one of the left bundle branch
      block electrocardiograms would otherwise be falsely classified as anterior
      myocardial infarction by the network. Artificial neural networks can be trained
      to indicate 'lack of experience', and this ability increases the possibility for
      neural networks to be accepted as reliable decision support systems in clinical
      practice.

PMID- 9568354
TI  - Menopause is associated with the stiffness of the common carotid artery in 50
      year-old women.
AB  - To determine if menopause has an effect on the elasticity of the arteries, the
      stiffness index of the common carotid artery was studied in 84 premenopausal and
      139 post-menopausal women. The study group was age-homogeneous, all women being
      50 years of age. There were no significant differences between pre- and post
      menopausal women regarding atherosclerosis, when measured as the number of
      subjects with plaques or intimal-medial thickness. The diameter of the common
      carotid artery was significantly larger in post-menopausal women. The diameter
      was correlated to measurements of body size which did not, however, differ
      between the two groups. The mean stiffness indexes were 4.99 +/- 1.02 and 5.38 +/
      1.21 in the pre- and post-menopausal groups respectively (P < 0.05). In a
      multivariate analysis, menopause (P < 0.05), and also serum insulin levels (P <
      0.01) and smoking (P < 0.05) were found to have independent significant
      associations to the stiffness index. In conclusion, menopause is associated with
      reduced elasticity of the carotid arteries in 50-year-old women.

PMID- 9568355
TI  - Analogue and digital electrocardiogram recordings in the assessment of heart rate
      variability.
AB  - We compared analogue and digital 24-h electrocardiogram (ECG) recordings in the
      assessment of heart rate variability (HRV) in 41 patients with suspected coronary
      artery disease. The patients underwent ambulatory ECG recordings simultaneously
      with analogue (A) (Marquette 8500) and digital (D) (Oxford Medilog FD-3)
      recorders. Digital ECG recordings were analysed with the Excel Medilog II system
      (DE) and analogue recordings were analysed with both Marquette (AM) and Excel
      Medilog II (AE) systems. SDNN, SDANN, rMSSD and pNN50 were calculated for the
      assessment of time domain measures of HRV, and powers of low (0.04-0.15 Hz) and
      high (0.15-0.40 Hz) spectral components of HRV for the assessment of frequency
      domain measures of HRV. Correlations between time domain measures of HRV derived
      from AM, AE and DE recording and analysis techniques were high (r = 0.803-0.999,
      P < 0.001). SDANN and pNN50 assessed with AM and DE were equal, whereas SDNN and
      rMSSD values differed slightly but significantly from each other (P < 0.01 for
      both). All time domain measures of HRV assessed with AE differed significantly
      from AM (P < 0.001) and from DE (P < 0.01). Correlations between frequency domain
      measures of HRV derived from AM, AE and DE were also high (r = 0.973-0.992, P <
      0.001). Despite this, frequency domain measures of HRV assessed with AM, AE and
      DE differed significantly from each other (P < 0.001). In conclusion, when
      analysed with their own analysis systems, analogue and digital recordings
      provided almost identical time domain, but not frequency domain, measures of HRV.
      In addition, analysis of an ECG recording with an analysis system of different
      manufacturer should be avoided.

PMID- 9568356
TI  - Plasma vitellogenin of grouper (Epinephelus malabaricus): isolation and
      properties.
AB  - Radiolabelled vitellogenin produced by juvenile grouper following injection of 3H
      leucine, 32P-orthophosphate and estradiol-stimulation was purified by anion
      exchange and gel filtration chromatography and characterized by electrophoresis
      and chemical analysis. The radiolabelled product was found to exist in two
      heterogeneous molecular weight forms by electrophoresis under nondenaturing
      conditions on polyacrylamide gel with M(r), of 260,000 and 525,000. It showed two
      protein monomers (M(r) 113,000 and 140,000) on electrophoresis under denaturing
      condition on a sodium dodecyl sulphate-polyacrylamide gel. The purified material
      contained 17.2% total lipid with 1.3% cholesterol and 2.1% triglycerides, 8-21
      micrograms/mg protein total carbohydrate and 6.8 micrograms phosphate/mg protein;
      amino acid analysis showed a profile comparable to that found for vitellogenins
      isolated from the grouper, medaka, goldfish and rainbow trout. The study showed
      grouper vitellogenin to be a glycophospholipoprotein similar in composition to
      vitellogenins from other teleosts and demonstrated that vitellogenins can be
      induced in juveniles by injection with estradiol-17 beta.

PMID- 9568357
TI  - Cyclic AMP-dependent protein kinase in ovarian follicle cells of starfish
      Asterina pectinifera.
AB  - Adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) in
      ovarian follicle cells of the starfish Asterina pectinifera was studied. Protein
      kinase activity in follicle cell homogenate was activated by cAMP in a dose
      dependent manner, and Ka was obtained with 10(-7) M cAMP. The PKA activity
      required Mg2+ at concentrations between 2 and 10 mM. On Sephacryl S-300 column
      chromatography of partially purified PKA, Mr of the holoenzyme was estimated to
      be about 180,000. [2,3-3H]cAMP binding activity also suggested a regulatory
      subunit of Mr about 50,000. DE-52 column chromatography of the cell extract
      resolved the enzyme activity into two peaks, which eluted between 0.05 and 0.1 M
      NaCl (type I), and between 0.15 and 0.25 M NaCl (type II). The type I enzyme was
      the predominant form of PKA in starfish follicle cells. In a cell-free system, a
      70 kDa protein was phosphorylated during incubation with [gamma-32P]ATP in the
      presence of cAMP. These results suggest that PKA stimulates the phosphorylation
      of a 70 kDa protein following an increase in the level of cAMP.

PMID- 9568359
TI  - Dieldrin induces peroxisomal enzymes in fish (Sparus aurata) liver.
AB  - We have previously described the increase of microsomal lipid peroxidation and
      the appearance of new oxidized forms of Cu,Zn-superoxide dismutase in the liver
      of gilthead seabrams (Sparus aurata) injected with model xenobiotics, due to the
      increased production of reactive oxygen species (ROS) (Pedrajas et al., Chem.
      Biol. Interact., 1995). The effects of dieldrin and copper(II) on subcellular
      organelles directly related with ROS production are now studied. Immature fish
      were injected with dieldrin and copper, 0.15 and 1.0 mg/ kg, respectively. After
      2 and 7 days, the livers were homogenized and the catalase and superoxide
      dismutase activities were determined in subcellular fractions isolated by
      differential centrifugation: nucleus, mitochondria, light mitochondrial fraction
      (LMF), microsomes and cytosolic fraction. Peroxisomes were isolated from LMF by
      discontinuous gradient centrifugation using Nycodenz. Changes in catalase and
      superoxide dismutase depended on the xenobiotic and affected to different
      subcellular fractions. Thus, the effects of copper(II) were mainly in nucleus and
      cytosol, whereas dieldrin induced catalase and superoxide dismutase (up to 2.8
      fold) preferentially in nucleus and LMF fractions. Dieldrin-injected fish showed
      also highly increased activity of palmitoyl-CoA-oxidase (9.3-fold) and a nearly 2
      fold increase in the protein concentration of the peroxisomal fraction. The
      results described above suggest that the oxidative stress previously detected for
      dieldrin in fish liver affects also to the peroxisomal enzymes.

PMID- 9568358
TI  - The in vitro effects of forskolin, IBMX and cyanoketone on meiotic maturation in
      follicle-enclosed catfish (Clarias batrachus) oocytes.
AB  - The effects of an adenylate cyclase activator (forskolin, FK), phosphodiesterase
      inhibitor (3-isobutyl-l-methyl-xanthine, IBMX) and an inhibitor of
      steroidogenesis (cyanoketone, CK) on germinal vesicle breakdown (GVBD) in the
      catfish (Clarias batrachus) were investigated in vitro. In most of the
      experiments GVBD was induced by using 1 microgram/ml 17 alpha,20 beta-dihydroxy-4
      pregnen-3-one (17 alpha,20 beta-DP), which is the maturation-inducing steroid
      (MIS) for this species. Adenosine 3':5'-cyclic monophosphate (cAMP) levels were
      also measured in the control, MIS-induced and/or FK- and IBMX-treated follicle
      enclosed oocytes. MIS-induced GVBD was inhibited by FK (> or = 0.5 microM) or
      IBMX (> or = 1.0 mM), but oocyte exposed to 0.1 microM FK or 0.5 mM IBMX, after
      MIS stimulation, underwent GVBD. However, an inhibition of GVBD was recorded when
      the MIS-induced folliculated oocytes were preincubated with CK (1 microgram/ml)
      and subsequently treated with 0.1 microM FK. In the time course study, when the
      oocytes were stimulated by MIS for various time intervals and then treated with
      1.0 microM FK or 1.0 mM IBMX, both the substances blocked maturation if they were
      added up to 12 hr after MIS. The extent of inhibition was gradually decreased and
      was completely removed after 30 hr of post-MIS stimulation. The stimulatory dose
      of 17 alpha,20 beta-DP (1 microgram/ml) not only induced GVBD (83.2 +/- 1.50%) in
      vitro but also reduced oocyte cAMP level (65.3 +/- 2.85 pmol/100 micrograms
      protein) significantly after 6 hr of incubation. However, FK (10.0 microM) or
      IBMX (1.0 mM) countered these effects and promoted the accumulation of cAMP in
      the oocytes; FK being more potent. On the other hand, when unstimulated full
      grown but immature oocytes were cultured in vitro in the presence of different
      concentrations of FK, an induction of oocyte maturation was recorded in dose- and
      time-dependent manner. These results strongly suggest the involvement of cAMP in
      the regulation of catfish oocyte maturation.

PMID- 9568360
TI  - Growth hormone, gonad development, and steroid levels in female carp.
AB  - The pituitary and plasma growth hormone (GH) levels of female carp (Cyprinus
      carpio L.) were measured in fish of various sizes and degrees of maturity, and
      were matched against the levels of 17 beta-estradiol (E2), testosterone (T), 17
      alpha-hydroxyprogesterone (17-P), and progesterone (P) in the ovary and plasma.
      The short-term action of the above hormones and 17 alpha, 20 beta-dihydroxy-4
      pregnen-3-one (17,20-P) on the release of GH was examined in vitro in primary
      culture pituitary cells. The gonadosomatic index (%GSI) increased rapidly in
      specimens when they had attained 900 +/- 50 g body weight (BW). The pituitary and
      plasma GH levels increased between 150 and 600 g BW (when oocytes reached the
      stage at which lipoprotein appeared in the cytoplasm), but at 900 g BW (with
      oocytes in vitellogenesis) the plasma GH dropped, while pituitary GH remained
      high. E2 increased with BW, reaching its maximum at 600 and 900 g BW in the ovary
      and plasma, respectively. Similar patterns were found in the levels of T and P,
      both hormones reaching their maximum levels at 900 g BW. The level of 17-P was
      very low and did not increase in proportion to BW. The application of various
      concentrations of different steroids on a primary culture of pituitary cells led
      to release of GH. The highest degrees of release were obtained from 10(-6) and
      10(-7) M E2, 10(-6) M T, 10(-7) M 17-P and 10(-8) M 17,20-P. In all these cases,
      hormone treatment effected higher release of GH than was found in the control. A
      model of the relationship between GH and the steroids associated with maturation
      is proposed.

PMID- 9568361
TI  - Influence of prolactin on in vivo and in vitro lipolysis in rabbits.
AB  - Three experiments were conducted to assess the influence of prolactin on
      lipolysis in rabbits. In vivo, a single injection of 1 mg of ovine prolactin
      induces increased plasma glycerol and nonesterified fatty acids concentrations
      within 30 min (P < 0.01). On the contrary, in vitro, oPRL did not stimulate
      glycerol release in isolated adipocytes at physiological concentrations (under
      10(-8) M). In a third experiment, the effect of chronic hyperprolactinemia on the
      adrenergic control of lipolysis was studied (daily subcutaneous injections of 1
      mg ovine prolactin for 12 days). The weight of perirenal adipose tissue at the
      end of the period of injections was 27% lower in the prolactin-injected (PRL)
      rabbits than in the control (CTL) rabbits (88 +/- 15 g vs. 120 +/- 25 g; P <
      0.05). Food intake during the period of injections was 28% lower in the PRL group
      than in the CTL group (177 +/- 21 g/d vs. 246 +/- 13 g/d; P < 0.05). Basal
      glycerol release was 157% higher in adipocytes from PRL rabbits than in those
      from CTL rabbits (P < 0.05). Stimulation of lipolysis with different adrenergic
      agonists was similar in both groups. These results suggested an indirect
      influence of prolactin on adipose tissue lipolysis in rabbits, but mechanisms
      implicated in this effect remain to be elucidated.

PMID- 9568362
TI  - In vivo assessment of opioid agonists and antagonists on ovarian maturation in
      the red swamp crayfish, Procambarus clarkii.
AB  - The possible involvement of an endogenous opioid system in the regulation of
      ovarian development in the red swamp crayfish, Procambarus clarkii, was
      investigated in vivo. Injections of the opioid, methionine (Met) enkephalin, into
      females significantly slowed ovarian maturation in a dose-dependent manner. In
      contrast, injection of the general opioid antagonist, naloxone, produced dose
      dependent ovarian maturation. Furthermore, the highly selective delta opioid
      agonist, DADLE, also inhibited ovarian maturation, whereas a highly selective
      delta receptor antagonist, ICI-174,864, stimulated ovarian maturation. In view of
      these results and the fact that Met-enkephalin is a relatively selective delta
      receptor agonist, we hypothesize that in the crayfish the inhibitory effect of
      Met-enkephalin involves this type of binding site. Furthermore, it is
      hypothesized that the inhibitory action of these opioids is due to either (a)
      stimulation of release of the gonad-inhibiting hormone, (b) inhibition of release
      of the gonad-stimulating hormone or (c) both (a) and (b).

PMID- 9568363
TI  - Chemical and pharmacological characterization of halitoxin from Amphimedon
      viridis (Porifera) from the southeastern Brazilian coast.
AB  - The halitoxin complex from the marine sponge Amphimedon viridis, collected in the
      Sao Sebastiao channel (southeastern Brazilian coast), was isolated by gel
      filtration chromatography on Sephadex LH-20. Spectroscopic data (1H, 13C and 2D
      NMR) of halitoxin from A. viridis indicated that it has the same two
      alkylpyridine monomers composition of the previously isolated halitoxin from
      Amphimedon compressa (as Haliclona rubens). Nevertheless, analysis by High
      Performance Gel Permeation Chromatography indicated that the halitoxin complex of
      A. viridis has a lower molecular weight (500, 2000 and 5000 Da; the major
      component corresponding to the fraction of 2000 Da MW) when compared to the
      previously isolated halitoxin complex from A. compressa. Some pharmacological
      properties of the halitoxin complex from A. viridis were evaluated in terms of
      lethality, antimitosis, hemolysis and neurotoxicity. The possible chemotaxonomic
      value of alkyl pyridine alkaloids is discussed.

PMID- 9568364
TI  - Isoprenaline induces biosynthesis of proline-rich proteins in the salivary glands
      of rat but not in sheep.
AB  - Long-term treatment of rats with isoprenaline resulted in induction of proline
      rich proteins (PRPs) in the salivary glands, which were subsequently purified by
      TCA solubility and column chromatography. When rats were removed from beta
      agonist regimen, then these proteins were no longer observed. Treatment of sheep
      with isoprenaline did not reveal the induction of PRPs.

PMID- 9568365
TI  - Citral and testosterone interactions in inducing benign and atypical prostatic
      hyperplasia in rats.
AB  - Citral is a monoterpene in wide use as an aromatic supplement in the cosmetics
      and food industries. Previous studies in our laboratory have shown that cutaneous
      application of citral on adolescent rats may induce benign prostatic hyperplasia
      (BPH)-like and even atypical hyperplastic changes in the ventral lobes. In the
      present study we investigate the possible interactions between citral and serum
      testosterone levels on the induction of hyperplastic changes in the ventral
      prostate of adolescent rats. In addition, the study includes a comparative
      analysis of normal intact rats showing circadian variations of serum testosterone
      levels and rats in whom this rhythmic pattern was abolished either by excessive
      supplementation of exogenous androgen or by castration. Our results demonstrate
      an induction of benign as well as atypical prostatic hyperplasia following citral
      application. The most severe atypical changes were noted in the citral-treated
      rats with high serum testosterone levels. Although the mechanism of action of
      citral is yet unknown, the present results suggest a synergism between citral and
      testosterone resulting in hyperplastic changes in the rat ventral prostate. In
      addition, the results reconfirm that serum testosterone levels fluctuate
      according to a circadian rhythm in intact young and adolescent male rats. The
      application of citral tends to lower the morning circadian peaks, and the
      circadian pattern was abolished in orchiectomized rats and in those treated with
      testosterone implants.

PMID- 9568366
TI  - Comparison of ecdysteroid concentration in different morphs of aphids.
AB  - The amounts of ecdysteroids were determined in different morphs of holocyclic
      monoecious aphids (Acyrthosiphon pisum Harris, Dysaphis devecta Walk., Lachnus
      roboris L., Schizolachnus pineti F.) and holocyclic heteroecious aphids (Aphis
      sambuci L., Rhopalosiphum padi L.) by means enzyme immunoassay. Among the
      parthenogenetic morphs (fundatrices, virginoparae, and oviparae), the fundatrices
      have consistently higher amounts of ecdysteroids than those of other morphs of
      the same species. Alate and apterous virginoparae showed slight differences in
      their ecdysteroid titer both in heteroecious and monoecious aphids. The migrant
      morphs (i.e., alate fundatrices and gynoparae) have the lowest amounts of
      ecdysteroids within a species. With the exception of D. devecta, the oviparae of
      both heteroecious and monoecious aphids have the second greatest amounts of
      ecdysteroids among the morphs living on same host plant. Polyphenism, dispersal
      behavior, and fecundity in connection with weight, ovariole number, and
      ecdysteroid concentration of different morphs of aphids are discussed.

PMID- 9568367
TI  - Plasma angiotensin II, arginine vasopressin and atrial natriuretic peptide in
      free ranging and captive seals and sea lions.
AB  - We used radioimmunoassay methods to quantify arginine vasopressin (AVP), atrial
      natriuretic peptide (ANP), and angiotensin II (Ang II) in plasma samples from
      harbor seals (Phoca vitulina richardsii), Weddell seals (Leptonychotes
      weddellii), northern elephant seals (Mirounga angustirostris), ringed seals
      (Phoca hispida), California sea lions (Zalophus californianus), and Steller sea
      lions (Eumetopias jubatus). Plasma concentrations of AVP, ANP, and Ang II in
      these pinniped species were within the ranges reported for other vertebrates
      under resting conditions. However, there were species, geographic and
      developmental variations in these hormones: Levels of AVP in plasma samples from
      adult Steller sea lions and harbor seals were higher than in pups of the same
      species; higher levels of plasma ANP were found in wild captured Alaskan Steller
      sea lions and in hunted ringed seals; differences in plasma levels of all three
      hormones were found throughout the geographic distribution of harbor seals and
      Steller sea lions in Alaska. This is the first report on circulating
      concentrations of vasoactive hormones in pinnipeds, and demonstrates that further
      studies are needed to ascertain the natural variability in these levels with the
      impact of molting, fasting, diving and environmental factors in seals and sea
      lions.

PMID- 9568368
TI  - Changes in the plasma levels of vasoactive hormones during apnea in seals.
AB  - Prolonged and repetitive breath-hold periods (apnea) during and sleep are a
      routine component in the ecological physiology of marine mammals. Seals are among
      the few mammals in which control of heart rate (HR) can be studied independent of
      respiration, without pharmacochemical manipulation. We hypothesized that the
      vasoactive hormones angiotensin II (Ang II), arginine vasopressin (AVP), and
      atrial natriuretic peptide (ANP) were involved in the control of cardiovascular
      function in seals, and that the relationship was dependent upon input from the
      respiratory system. Venous plasma samples were collected and electrocardiograms
      were recorded from Northern elephant seal (Mirounga angustirostris) and Weddell
      seal (Leptonychotes weddellii) pups during both spontaneous breathing (eupnea)
      and apnea. Instantaneous HR and simultaneous plasma levels of ANP, AVP, and Ang
      II from periods of eupnea and apnea were compared. In these seal pups, apnea was
      associated with bradycardia, increased ANP, and decreased AVP and Ang II. The
      results support the hypothesis of a complex involvement between the vasoactive
      hormones and the control of cardiovascular function, and provide evidence for
      differential levels of control during periods of eupnea and apnea.

PMID- 9568369
TI  - Cholinergic mechanisms in the neurocontrol of the branchial heart of the
      cephalopod Sepia officinalis L.
AB  - Cholinergic mechanisms controlling the branchial heart of the cephalopod Sepia
      officinalis L. were examined. In vitro tests indicate that acetylcholine (ACh)
      exerts a dose-dependent negative inotropic and chronotropic effect. Although the
      nicotinic agonists carbachol and nicotine mimic the effects of ACh closely, the
      muscarinic agonists pilocarpine, muscarine and oxotremorine induce only a slight
      inhibition of amplitude and frequency. Other agents tested (including atropine,
      pirencepine, hexamethonium, tetraethylammonium (TEA), d-tubocurarine and alpha
      bungarotoxin) confirm that the acetylcholine receptor in branchial heart muscle
      is probably nicotinic.

PMID- 9568370
TI  - Seasonal changes in adrenal sensitivity alter corticosterone levels in Gambel's
      white-crowned sparrows (Zonotrichia leucophrys gambelii).
AB  - Recent work indicates that Gambel's white-crowned sparrows modulate
      corticosterone release seasonally in response to capture and restraint. Free
      living white-crowned sparrows dramatically elevate both baseline and stress
      induced corticosterone levels during the breeding season compared with either
      wintering or migrating birds. Although corticosteroid binding globulin capacity
      also rises during breeding, it does not fully compensate for elevated
      glucocorticoid levels. Consequently, we examined what hypothalamic-pituitary
      adrenal axis changes could account for seasonal changes in glucocorticoid levels.
      During winter and fall migration, exogenous ACTH failed to elevate corticosterone
      levels beyond the response to capture and handling, suggesting that the adrenal's
      ability to release corticosterone limits circulating levels during these seasons.
      In contrast, not only were corticosterone levels higher during breeding, but
      adrenals further responded to an exogenous ACTH signal, indicating a dramatic
      enhancement of the adrenal's ability to secrete corticosterone. Furthermore, we
      inferred the pituitary's ACTH secretory ability by injecting exogenous
      corticotrophin-releasing factor (CRF), arginine vasotocin (AVT) and mesotocin and
      measured corticosterone release. Pituitaries in breeding birds appear to respond
      to exogenous CRF and AVT, suggesting hypothalamic control of corticosterone
      release during this season. Taken together, these results suggest that seasonal
      modulation of corticosterone release in this species is controlled primarily at
      the adrenal.

PMID- 9568371
TI  - Annual and diurnal variations in, and effects of altered photoperiod and
      temperature, ovariectomy, and estradiol-17 beta replacement on catechol-O
      methyltransferase level in brain regions of the catfish, Heteropneustes fossilis.
AB  - The annual data show that catechol-O-methyltransferase (COMT) content increases
      with the progress of ovarian recrudescence in all the brain regions
      (telencephalon, hypothalamus, thalamus + tegmentum, and medulla oblongata) and
      declines after spawning to low values in quiescent phase. Diurnal variation in
      enzyme concentration with peak values at 24 hr was noticed in the hypothalamus
      throughout the reproductive cycle; in other brain regions, it was observed only
      in February and March. The stimulatory response of the enzyme to photoperiod and
      temperature alterations was differential and region-specific; an effect of
      photoperiod change was noticed only in the hypothalamus and was less in magnitude
      compared to the temperature effect. The response of the enzyme to ovariectomy
      (OVX) and E2 supplementation was region-specific (hypothalamus only), season
      specific (prespawning phase), and varied:inhibitory at 3 and 4 weeks, stimulatory
      at 6-week of OVX and after 0.05, 0.1, 5, and 10 micrograms/g doses of E2, and
      none at week 2 and 5 of OVX and after 0.5 and 1 microgram/g doses of E2. The
      season-specific changes in hypothalamic COMT may be indicative of its involvement
      in catecholamine (and possibly catecholestrogen)-mediated neuroendocrine control
      of gonadotropin.

PMID- 9568372
TI  - Isolation and characterization of new GalNAc/Gal-specific lectin from the sea
      mussel Crenomytilus grayanus.
AB  - A lectin, Crenomytilus grayanus (CGL), was purified from sea mussel C. grayanus
      by affinity chromatography on acid-treated Sepharose 6B and following gel
      filtration on Sephacryl S-200. Molecular weight of the lectin obtained was
      determined by SDS-PAGE to be 18,000, independent of the presence or absence of
      beta-mercaptoethanol. CGL was found to agglutinate all types of the human
      erythrocytes together with mouse and rabbit. In hemagglutination inhibition
      assays, N-acetyl-D-galactosamine, D-galactose, and D-talose were the most potent
      inhibitors among the monosaccharides tested. Out of the oligosaccharides
      containing nonreducing terminal D-galactose, melibiose, and raffinose were found
      to be strong inhibitors. On the other hand, among the glycoproteins, asialo-BSM
      was the best inhibitor. The hemagglutinating activity of CGL was independent of
      the divalent cations Ca2+ and Mg2+. Significant CGL activity was observed between
      pH 8-10.

PMID- 9568373
TI  - Effects of hypoxia and toxicant exposure on adenylate energy charge and cytosolic
      ADP concentrations in abalone.
AB  - Many studies have used adenylate energy charge (AEC) as an index of an organism's
      metabolic state under conditions of imposed stress, either through natural or
      xenobiotic stressors. AEC is a linear measure of the ratio of ATP concentration
      to total adenylate concentration, which ranges in value from 1 in the fully
      charged state to 0. Paradoxically, high values of AEC are often associated with
      high toxicant exposures, and low AEC values with low exposures. These
      discrepancies may be caused by the inability of AEC measurements to adequately
      evaluate cytosolic adenylate concentrations, which are the critical parameters in
      enzymatic regulation. Consequently, the goal of this study was to compare AEC
      values, as measured by high performance liquid chromatography (HPLC), to free
      adenosine diphosphate (ADPfree) concentrations, as measured using the arginine
      kinase equilibrium reaction and in vivo 31P-NMR, in red abalone (Haliotis
      rufescens) in response to either hypoxia or toxicant (pentachlorophenol, or
      sodium azide) exposure. AEC values remain essentially constant when compared with
      control animals during periods of stress exposure and recovery. In contrast,
      calculated ADPfree concentrations are approximately a third of those determined
      by HPLC and nearly double in response to stress exposure. The physiologic
      importance of this response is demonstrated by increases in ATP formation via
      arginine kinase. These results are discussed in light of the pertinent mammalian
      literature.

PMID- 9568374
TI  - Ischemia and ischemic preconditioning in the buffer-perfused pigeon heart.
AB  - Isolated pigeon hearts were perfused with Krebs-Henseleit bicarbonate buffer with
      1.25 mM Ca++ at a pressure of 60 cm H2O and paced at 210 beats per min. After an
      equilibration perfusion of 30 min, hearts were subjected to 10 min global
      ischemia and then reperfused for 30 min. Left ventricular +dP/dtmax, systolic,
      and end diastolic pressures differed significantly from baseline values during
      reperfusion as did the release of lactate dehydrogenase (LDH). When the hearts
      were preconditioned by interruption of flow for two 2.5-min intervals, followed
      by 10 min of ischemia and then reperfusion, the short periods of ischemia,
      followed by reperfusion, protected the hearts against the longer bout of ischemia
      as evidenced by significant differences between the left ventricular (LV)
      pressure, +dP/dtmax, LV end diastolic pressure and LDH values obtained from the
      hearts of control vs. preconditioned hearts. Substitution of 1 microM adenosine
      for the preconditioning ischemia also resulted in the preconditioning response.
      Ischemic preconditioning (IP) was not blocked by addition of 100 microM 8-(-p
      sulfophenyl) theophylline, an adenosine receptor antagonist. Therefore, isolated,
      perfused bird hearts can be preconditioned, and the mechanism may involve
      adenosine receptors, although their activation is not necessary for i.p. to
      occur. Factors in addition to adenosine are likely involved.

PMID- 9568375
TI  - Response of superoxide dismutase to pollutant metal stress in the marine
      dinoflagellate Gonyaulax polyedra.
AB  - The response of superoxide dismutase (SOD) activity in the marine dinoflagellate
      Gonyaulax polyedra to chronic (5.0 ppb Hg, 0.5 ppm Cd, 2.0 ppm Pb and 0.1 ppm Cu,
      during 30 days) and acute (10.0 ppb Hg, 1.0 ppm Cd, 5.0 ppm Pb and 0.25 ppm Cu,
      during 48 hours) exposure to metals was investigated. Under chronic exposure to
      Hg, Cd, Pb, and Cu, total SOD activity of metal-treated cells increased during
      the first day of exposure to plateau levels of 134, 148, 127, and 139% of control
      values respectively. Under acute metal exposure, SOD activity increases were of
      similar magnitude but much more rapid (within several hours) and of shorter
      duration. In addition, assays for oxidative damage to lipids revealed high levels
      of lipid peroxidation in cells kept in either chronic or acute exposure to metals
      reaching values 2-fold greater than the control group. Changes in SOD activity
      were dependent on the metal, its concentration, and the time of exposure. Non
      denaturing polyacrylamide gels revealed induction of Fe-SOD and Mn-SOD but not Cu
      Zn-SOD isoforms in cells kept under acute exposure to metals. These results
      suggest that oxidative stress may be an important mediator of metal toxicity in
      algal systems, with SOD providing antioxidant protection.

PMID- 9568376
TI  - The effect of insulin-like growth factor-I (IGF-I) on protein turnover in the
      meat-type chicken (Gallus domesticus).
AB  - Insulin-like growth factor-I (IGF-I) effects on chicken growth and development
      are poorly understood. This study examined the effect of IGF-I on protein
      synthesis rates in various tissues in the male broiler chicken. At three weeks of
      age, osmotic minipumps were subcutaneously implanted in the scapular area.
      Chickens were infused with either chicken IGF-I (450 micrograms/kg BW/day) or
      saline. After treatment for 5 days, the chickens received a flooding dose of [3H]
      phenylalanine, and were sacrificed 20 min later. Wing vein blood samples were
      taken at 0, 5, 10 and 20 min post-injection. The following tissues were removed
      and frozen for analysis: pectoralis muscle, gastrocnemius muscle, heart, liver,
      and small intestine. In vivo total protein synthesis measurements were made using
      the double-label technique. Contractile protein degradation was evaluated using
      intracellular free 3-methylhistidine concentrations in skeletal muscle. There
      were no significant differences in absolute or relative body growth rates over
      the treatment period. Skeletal muscle (pectoralis and gastrocnemius) weights were
      significantly decreased with IGF-I treatment, while heart weight was
      significantly increased. Plasma insulin levels were significantly lower in IGF
      treated chickens compared to that in control birds. There was no effect of IGF-I
      on protein synthesis rates in any of the tissues examined. Intracellular free 3
      methylhistidine concentrations were higher in both the gastrocnemius (17%) and
      pectoralis muscles (25%) of chickens treated with IGF-I. This data demonstrates
      that IGF-I may have an indirect effect to regulate muscle protein turnover rates.

PMID- 9568377
TI  - Reduced macrophage phagocytic activity in Wolffian lens regeneration of the newt
      after nickel subsulfide administration.
AB  - The inhibition of newt lens regeneration by intraocular injection of nickel
      subsulfide (alpha Ni3S2), a potent carcinogen, was shown in our previous studies.
      In the present study, we examined the effect of nickel subsulfide on macrophages
      involved in depigmentation in the early stages of regeneration using light and
      electron microscopic observations on semithin (1.5 microns) and ultrathin
      sections. Phagocytic activity of macrophages in ingestion of pigment granules
      from pigmented dorsal iris epithelial cells was much reduced in the carcinogen
      treated eyes, whereas the change in their number and pattern accumulating in the
      iris during lens regeneration was generally the same as in untreated eyes.

PMID- 9568378
TI  - Effects of protein kinase A inhibitor (H-89) on VIP- and GRF-induced release and
      mRNA expression of prolactin and growth hormone in the chicken pituitary gland.
AB  - Vasoactive intestine polypeptide (VIP) and growth hormone releasing factor (GRF)
      stimulated an increase of cAMP accumulation with a concomitant release of PRL and
      GH, respectively. Release of PRL induced by VIP was partially suppressed by 5 and
      25 microM of H-89, whereas VIP-induced gene expression of PRL was inhibited by
      all concentrations of H-89. Release and gene expression of GH induced by GRF was
      inhibited by H-89 in a dose-dependent manner and completely blocked by 25 microM
      of H-89. These results indicate that VIP-induced PRL release and gene expression
      may be mediated, at least in a part, by cAMP-dependent protein kinase pathway,
      whereas GRF-induced GH release and gene expression may be mediated predominantly
      by cAMP-dependent protein kinase.

PMID- 9568379
TI  - Effects of hexamethonium, phenothiazines, propranolol and ephedrine on
      acetylcholinesterase carbamylation by physostigmine, aldicarb and carbaryl:
      interaction between the active site and the functionally distinct peripheral
      sites in acetylcholinesterase.
AB  - Physostigmine, aldicarb and carbaryl were potent inhibitors of
      acetylcholinesterase (AChE). The physostigmine-inhibited AChE fluoresced at 300
      nm excitation and 500 nm emission wavelengths, but the aldicarb and carbaryl
      inhibited enzyme did not. This suggests that the carbamylated active center is
      not the fluorescing site in AChE. The fluorescence intensity of physostigmine
      inhibited AChE decreased with increasing the substrate (acetylthiocholine)
      concentration, thus indicating that physostigmine binding to the active site is
      essential for the development of fluorescence. Thus, the physostigmine-inhibited
      AChE fluoresces due to the binding of trimethylpyrrolo[2,3-b]indol (TMPI) moiety,
      formed by the hydrolysis of physostigmine, to a peripheral site in AChE. The
      fluorescence intensity of the physostigmine-inhibited enzyme decreased when the
      inhibited-enzyme was dialyzed for either 30 min that poorly reactivated the
      enzyme or 180 min that fully reactivated the enzyme. This suggests that dialysis
      dissociates the AChE-TMPI complex much faster than it reactivates the
      carbamylated AChE. Ephedrine, propranolol and phenothiazines including
      trifluoparazine (TPZ) caused non-competitive inhibition, while hexamethonium
      caused an uncompetitive inhibition of AChE activity. TPZ, upon binding with AChE,
      formed a fluorescent TPZ-enzyme complex. The fluorescence intensity of TPZ-AChE
      complex was effectively decreased by ephedrine, but not by propranolol or
      hexamethonium. This indicates that TPZ and ephedrine bind to the same site in
      AChE which is different from the site/or sites to which propranolol or
      hexamethonium bind. Hexamethonium protected AChE from inhibition by carbamates
      and decreased the fluorescence intensity of the physostigmine-inhibited AChE.
      Phenothiazines and ephedrine did not modulate the enzyme inhibition or the
      fluorescence intensity of the physostigmine-inhibited AChE. Propranolol and TPZ
      potentiated the enzyme inhibition and increased the fluorescence intensity in the
      presence of physostigmine. These compounds, however, did not affect the
      inhibition of AChE by carbaryl or aldicarb. Ephedrine blocked the effects of TPZ,
      but did not alter the effects of propranolol on physostigmine-inhibited AChE.
      AChE, therefore, contains multiple peripheral binding sites which, upon binding
      to specific ligands, transduce differential signals to the active center.

PMID- 9568380
TI  - Physicochemical, molecular-orbital and electronic properties of acephate and
      methamidophos.
AB  - Methamidophos (Me) and its N-acetylated derivative, acephate (Ac), are water
      soluble insecticides that have similar insecticidal potency, but different
      mammalian toxicity. Me is a potent inhibitor, while Ac is a poor inhibitor of
      mammalian AChE (mAChE). At physiological pH, both insecticides exhibit similar
      accumulation in RBC, while Ac exhibits greater binding to plasma proteins than
      Me. These differential effects of Ac and Me are attributed to the differences in
      their physicochemical, molecular-orbital and electronic properties. Ac and Me are
      freely soluble in aqueous solution, moderately soluble in ethyl-acetate (EtAct)
      and insoluble in n-hexane. The solubility of these insecticides in aqueous
      solution and the partitioning of these insecticides from aqueous solution into
      EtAct are independent of the pH of the aqueous solution. At pH 8, Me did not
      react with o-phthalaldehyde (a NH2 selective dye), but gamma-amino-butyric acid
      (pKa 10) did. Thus, despite the presence of an amino group, Ac and Me do not
      exhibit pH dependent solubility in aqueous and in organic solvents. Ac has two O
      atoms with non-bonding electrons (P = O delta- and C = O delta-) where P = O and
      C = O point in opposite directions. Me has only one O atom with non-bonding
      electrons (P = O delta-). However, because of charge translocation, the C = O
      group of Ac exists as C = O- and the P-NH3+ group of Me exists as P = NH2+ at a
      pH lower than their pKa. The P-N bond of Me, but not of Ac, is hydrolyzed at pH
      2. Thus, the presence of an electron rich domain stabilizes Ac's P-N bond. The
      CH3S-P bond of both insecticides is similarly hydrolyzed at pH 11. This indicates
      that the two compounds are considerably similar except that Ac has an additional
      electron rich domain. At physiological pH, therefore, the functional differences
      between these insecticides may be due to the differences in their electronic
      structure. We propose that, similar to a previous model for cationic inhibitors
      of AChE (13), the P = O delta- group of Me forms hydrogen bonds within the
      oxyanion-hole causing the leaving group (-SCH3) to orient towards the "gorge"
      opening. This orientation allows the P atom of Me to interact with Ser200,
      resulting in the phosphorylation of the enzyme. For acephate, either P = O or C =
      O, but not both, interact within the oxyanion-hole. This destabilizes the binding
      of Ac to the active center, resulting in reduced AChE phosphorylation.

PMID- 9568381
TI  - A web access script language to support clinical application development.
AB  - This paper describes the development of a script language to support the
      implementation of decentralized, clinical information applications on the World
      Wide Web (Web). The goal of this work is to facilitate construction of low
      overhead, fully functional clinical information systems that can be accessed
      anywhere by low cost Web browsers to search, retrieve and analyze stored patient
      data. The Web provides a model of network access to data bases on a global scale.
      Although it was originally conceived as a means to exchange scientific documents,
      Web browsers and servers currently support access to a wide variety of audio,
      video, graphical and text based data to a rapidly growing community. Access to
      these services is via inexpensive client software browsers that connect to
      servers by means of the open architecture of the Internet. In this paper, the
      design and implementation of a script language that supports the development of
      low cost, Web-based, distributed clinical information systems for both Inter- and
      Intra-Net use is presented. The language is based on the Mumps language and,
      consequently, supports many legacy applications with few modifications. Several
      enhancements, however, have been made to support modern programming practices and
      the Web interface. The interpreter for the language also supports standalone
      program execution on Unix, MS-Windows, OS/2 and other operating systems.

PMID- 9568382
TI  - Analytical validation of the BEM--application of the BEM to the
      electrocardiographic forward and inverse problem.
AB  - The objective of this study is to analytically validate a boundary element (BE)
      formulation for the relationship between the transmembrane potential on the
      heart's surface and the potential on the body surface applying a concentric
      spherical test geometry. The relative difference (reldif) between the potential
      on the outer sphere of the test geometry computed analytically and numerically is
      determined by 3.59% for the coarse discretization (48 BEs) and by 0.46% in the
      case of the finer subdivision (192 BEs). In the inverse problem, the
      transmembrane potential on the inner sphere is estimated numerically from the
      electric potential on the outer sphere by using a minimum-norm least-square
      approach. The relative differences found are 20.2% when no measurement noise is
      added and 26.4% in the presence of 2% additional Gaussian noise. The BE
      formulation is also applied to real world data for solving the
      electrocardiographic inverse problem. A normal volunteer's inhomogeneous thorax
      (outer thorax surface, surfaces of the lungs, epicardial heart surface) is
      modelled by 424 BEs. The same inverse method is then applied in order to
      reconstruct the transmembrane potential on the epicardium from the measured body
      surface potential (BSP) data during normal ventricular depolarisation.

PMID- 9568383
TI  - Standardized structure and modular design of a pharmacokinetic database.
AB  - BACKGROUND: The accumulated knowledge on drugs can be used for an individual drug
      dosage adjustment if it is placed at our disposal in an informatically structured
      form. THEORY AND METHODS: We have started building up a pharmacokinetic database
      aimed at adjusting drug dosages, in exemplary form, to patients with renal
      impairment. Parameters needed for the three dosage adjustment rules (Dettli,
      Kunin, Holford) and the most general concept of pharmacokinetics constituted the
      theoretical basis. TWO PROCESSES PERTAIN TO ALL DRUGS: Distribution and
      elimination. Total drug clearance and at least two parameters representing
      distribution and elimination processes are closely interdependent in mathematical
      terms (clearance = volume of distribution*rate of elimination). This relation
      yields the unifying concept that serves as a prerequisite for a structured
      recording of 30 assigned pharmacokinetic and pharmacodynamic parameters within an
      informatic database. SOLUTIONS AND RESULTS: The information is retrieved and
      referenced from 2383 original publications by means of a standardized input
      module. The complete database at present contains 15,397 records for 1573 drugs.
      A programmed meta-analytic algorithm is used to calculate the statistical
      measures for the central value and variance--as available--from the pooled values
      of primary records. The statistically standardized parameters are extracted for
      6601 pharmacokinetic parameters, and placed at the users disposal with the output
      module. PRACTICAL UTILITY: Following meta-analysis, published pharmacokinetics
      can be used as statistical estimates of population parameters. The statistical
      estimates with variances permit an individual drug dosage adjustment by applying
      the Bayesian approach or neural networks.

PMID- 9568384
TI  - Ultrasound characterization by stable statistical patterns.
AB  - It is shown that automated characterization of ultrasound images can be achieved
      effectively if the images are confined to single internal organs. The ultrasound
      image of a particular organ gives statistical textures of its structures, which
      are consistent with stable patterns. Analysis of these patterns leads to the
      construction, from a few statistical parameters, of a fast and effective
      algorithm to characterize these ultrasound images. A small training set is
      adequate. A similar approach may be used to detect tumour sites from liver
      ultrasonograms. The algorithms are implemented on an IBM-compatible personal
      computer for future incorporation into existing ultrasound machines.

PMID- 9568385
TI  - Mixed quantitative/qualitative modeling and simulation of the cardiovascular
      system.
AB  - The cardiovascular system is composed of the hemodynamical system and the central
      nervous system (CNS) control. Whereas the structure and functioning of the
      hemodynamical system are well known and a number of quantitative models have
      already been developed that capture the behavior of the hemodynamical system
      fairly accurately, the CNS control is, at present, still not completely
      understood and no good deductive models exist that are able to describe the CNS
      control from physical and physiological principles. The use of qualitative
      methodologies may offer an interesting alternative to quantitative modeling
      approaches for inductively capturing the behavior of the CNS control. In this
      paper, a qualitative model of the CNS control of the cardiovascular system is
      developed by means of the fuzzy inductive reasoning (FIR) methodology. FIR is a
      fairly new modeling technique that is based on the general system problem solving
      (GSPS) methodology developed by G.J. Klir (Architecture of Systems Problem
      Solving, Plenum Press, New York, 1985). Previous investigations have demonstrated
      the applicability of this approach to modeling and simulating systems, the
      structure of which is partially or totally unknown. In this paper, five separate
      controller models for different control actuations are described that have been
      identified independently using the FIR methodology. Then the loop between the
      hemodynamical system, modeled by means of differential equations, and the CNS
      control, modeled in terms of five FIR models, is closed, in order to study the
      behavior of the cardiovascular system as a whole. The model described in this
      paper has been validated for a single patient only.

PMID- 9568386
TI  - Development Web alert.

PMID- 9568387
TI  - Development. Editorial overview.

PMID- 9568388
TI  - Patterning of the embryonic forebrain.
AB  - The vertebrate forebrain is derived from the anterior neural plate, where
      anteroposterior, dorsoventral and local patterning mechanisms specify regional
      identify. The recent identification of genetic regulators of these processes has
      opened the way to elucidating how the major forebrain regions (i.e. cerebral
      cortex, basal ganglia, thalamus, and hypothalamus) are formed, and how molecular
      lesions in these processes cause human birth defects.

PMID- 9568389
TI  - Neuronal diversification: development of motor neuron subtypes.
AB  - Recent progress has been made in defining the developmental mechanisms that
      contribute to the diversification of motor neuron subtypes, which differ in
      transcription factor gene expression and synaptic connections. These studies
      suggest that progenitor cells acquire specific motor neuron identities through
      the coordinate actions of multiple factors. Current evidence suggests that Sonic
      hedgehog initiates a common pathway for motor neuron differentiation, while
      positionally distributed factors act to assign subtype identities.

PMID- 9568390
TI  - Neural progenitors and stem cells: mechanisms of progenitor heterogeneity.
AB  - Heterogeneity among progenitor cells in the vertebrate nervous system has been
      documented with increasing frequency over the past few years. It has become clear
      that differences in progenitor cells help to determine when and how they respond
      to environmental signals. More recent studies have begun to elucidate the
      molecular basis of the differences in progenitor cell subpopulations that control
      their developmental potential and responsiveness to environmental signals.

PMID- 9568391
TI  - New directions for neuronal migration.
AB  - Analysis of genetic mutations that lead to abnormal migration and layer formation
      in the developing cerebral cortex of mice and humans has led to important new
      discoveries regarding the molecular mechanisms that underlie these processes.
      Genetic manipulation and experimental analysis have demonstrated significant
      tangential migrations of cortical neurons, some arriving from very distant
      noncortical sites.

PMID- 9568392
TI  - Sealing one's fate: control of cell death in neurons.
AB  - BCL-2 family members and caspases are essential components of the death machinery
      in neurons. Identification of Apaf-1 as the mammalian homologue of Caenorhabditis
      elegans ced-4 provided the final proof of the complete conservation of the C.
      elegans programmed cell death pathway in mammals. When neurons are deprived of
      trophic factors, a sequence of events is initiated, which includes a reduction in
      macromolecule synthesis, elevation of c-Jun and cyclin D1, and activation of BAX.
      The final episode of this sequence is the activation of caspases, which may mark
      the death commitment point at which neurons cannot be rescued by addition of
      trophic factors. In addition, recent evidence suggests that the components in the
      developmental programmed cell death pathway may play a critical role in
      neurodegenerative disorders.

PMID- 9568393
TI  - Axon guidance to and from choice points.
AB  - Significant progress has been made recently in understanding axon guidance to and
      from choice points. Netrins have been shown to function as conserved midline
      chemoattractants in vertebrates and insects, and receptors for netrins and
      semaphorins/collapsins have been identified. More evidence has accumulated that
      repulsion plays a key role in guidance, including the involvement of the
      ephrin/Eph receptor system in contact repulsion.

PMID- 9568394
TI  - Axon guidance at choice points.
AB  - The common theme in many recent axonal pathfinding studies, both in vertebrates
      and invertebrates, is the demonstration of the importance of a balance between
      positive and negative cues. The integration of multiple and often opposing
      molecular interactions at each site along the axon's trajectory, especially at
      choice points, helps to fine tune the directional response of its growth cone,
      which continuously samples its environment for guidance cues. The dynamic
      regulation of the receptors for such cues, in response to extrinsic signals, also
      enhances the behavioral repertoire of growth cones at different points along
      their trajectory. Some of the molecules identified as being important for axon
      guidance at choice points are conserved between invertebrates and vertebrates
      (e.g. Robo and netrin), whereas other molecules have been identified, so far,
      only in invertebrates (e.g. Comm) or vertebrates (e.g. axonin-1 and NrCAM).

PMID- 9568395
TI  - Adhesion and signaling in axonal fasciculation.
AB  - Numerous in vitro assays and in vivo perturbation studies have led to a model of
      neural development in which selective fasciculation helps to define accurate
      axonal projections. Genetic analysis in vivo confirms the hypothesis that axonal
      fasciculation and defasciculation are controlled by adhesion mechanisms, but also
      suggests that, in many cases, adhesion and guidance are separable phenomena. In
      addition, receptors that control the level of tyrosine phosphorylation may play
      an important role in fasciculation, suggesting that complex intracellular
      pathways lie just beneath the surface.

PMID- 9568396
TI  - Neural cell recognition molecule L1: from cell biology to human hereditary brain
      malformations.
AB  - The neural cell recognition molecule L1 is a member of the immunoglobulin
      superfamily implicated in embryonic brain development. L1 is engaged in complex
      extracellular interactions, with multiple binding partners on cell surfaces and
      in the extracellular matrix. It is the founder of a neural group of related cell
      surface receptors that share with L1 a highly conserved cytoplasmic domain that
      associates with the cytoskeleton. Phenotypic analyses of human patients with
      mutations in the L1 gene and characterizations of L1-deficient mice suggest that
      L1 is important for embryonic brain histogenesis, in particular the development
      of axon tracts.

PMID- 9568397
TI  - Target selection: invasion, mapping and cell choice.
AB  - Recent research has shown that changes in the concentration of particular
      molecules lead axons to invade their target, and that concentration changes in
      other molecules at the borders of the target prevent axons from leaving the
      target area. After invasion, topographic and lamina-specific cues guide axons to
      the correct location within the target field. At the level of a single cell or
      part of a cell, the evidence raises the possibility that axon targeting might be
      a combinatorial affair whereby specific axons compare the relative concentrations
      of several molecules on the surface of postsynaptic cells in order to choose a
      particular target. Both proteins and carbohydrates of various classes play major
      roles in these processes.

PMID- 9568398
TI  - An emerging link between cytoskeletal dynamics and cell adhesion molecules in
      growth cone guidance.
AB  - It has become increasingly evident that growth cone guidance depends on the
      concerted actions of cytoskeletal proteins, molecular motors and cell adhesion
      molecules. Recent studies suggest that modulation of coupling between
      extracellular substrates and intracellular cytoskeletal networks via cell surface
      receptors is an important mechanism for regulating directed neuronal growth.

PMID- 9568399
TI  - Cell-contact-dependent signalling in axon growth and guidance: Eph receptor
      tyrosine kinases and receptor protein tyrosine phosphatase beta.
AB  - The growth and guidance of axons involves the recognition of complex
      environmental cues by receptor proteins on the surface of the growth cone and
      their interpretation by cellular machinery, leading to changes in cellular
      behaviour. Recent advances have demonstrated that the ligands for Eph receptor
      tyrosine kinases, the ephrins, act as repulsive axon guidance cues, and that Eph
      receptors are required for correct axonal navigation in vivo. Members of the
      receptor protein tyrosine phosphatase (RPTP) family also play important roles in
      axon guidance and growth. RPTP beta and Eph receptors interact with cell-surface
      bound ligands, and there is increasing evidence that both transmembrane ephrins
      and contactin, a ligand for RPTP beta, may possess an intrinsic signalling
      function. Thus, the cell-contact-dependent interactions between these receptors
      and ligands may lead to initiation of bidirectional signals that regulate axonal
      growth and migration.

PMID- 9568400
TI  - Forward and reverse genetic approaches to synaptogenesis.
AB  - Genetic approaches at the neuromuscular synapse are leading investigation into
      the mechanisms of synaptogenesis. The marriage of classical (forward) and reverse
      genetic techniques allows the isolation and analysis of novel proteins involved
      in synaptic maturation and the functional in vivo characterization of previously
      identified synaptic proteins. Of particular interest are recent advances using
      mouse reverse genetics and Drosophila forward genetics.

PMID- 9568401
TI  - LTP and activity-dependent synaptogenesis: the more alike they are, the more
      different they become.
AB  - Recent data suggest that long-term potentiation and activity-dependent
      synaptogenesis share the same mechanism at the initiation stage during which NMDA
      receptor activity is necessary to increase the postsynaptic response via AMPA
      receptor currents. However, several fundamental differences between the
      environments of young and mature synapses and the neurons that support them
      suggest that the same cellular mechanism is facilitated by very different
      parameters in the young versus the mature brain.

PMID- 9568402
TI  - Genetic analysis of synaptic development and plasticity: homeostatic regulation
      of synaptic efficacy.
AB  - When experimentally challenged with perturbations in synaptic structure and
      function, neurons have the remarkable ability to regulate their synaptic efficacy
      back to the normal range. Recent genetic analysis has provided insights into the
      mechanisms controlling this form of synaptic homeostasis, with implications for
      our understanding of synaptic development and plasticity.

PMID- 9568403
TI  - Schizophrenia as a developmental disorder of the cerebral cortex.
AB  - The hypothesis that schizophrenia results from a developmental, as opposed to a
      degenerative, process affecting the cerebral cortex has become popular in current
      thinking about the disorder. While many of the data gathered in support of this
      hypothesis do not in themselves represent conclusive proof, an intriguing picture
      is emerging from a variety of research approaches. These approaches include the
      observation of minor physical anomalies, premorbid neuropsychological and social
      deficits, obstetrical complications, and exposure to adverse intrauterine events.
      Morphometric brain measurement techniques and neuropathological studies have
      perhaps provided more substantial support.

PMID- 9568404
TI  - Newer advances in the diagnosis and treatment of mitral stenosis.
AB  - There have been significant changes in presentation, diagnosis, and therapy of
      patients with mitral stenosis. Both the prevalence of mitral stenosis, as well as
      the type of patient now with mitral stenosis, have changed significantly over the
      past few decades. In patients with mitral stenosis two-dimensional and Doppler
      echocardiography have become the diagnostic modalities of choice. The advent of
      percutaneous mitral balloon valvotomy now provides a nonsurgical approach for the
      treatment of selected patients with mitral stenosis.

PMID- 9568405
TI  - Sequence-based diagnosis of tyrosinase-related oculocutaneous albinism:
      successful sequence analysis of the tyrosinase gene from blood spots dried on
      filter paper.
AB  - BACKGROUND: A large number of mutations of the tyrosinase gene result in
      oculocutaneous albinism (OCA). Therefore, at present, sequence analysis of the
      tyrosinase gene has become necessary to diagnose OCA patients and their
      relatives. OBJECTIVE: The aim of this study was to facilitate the sequence-based
      diagnosis of tyrosinase-related OCA by using small amounts of the patient's
      blood. METHODS: Blood spots dried on filter papers were used as sources of
      genomic DNA. The exons and flanking regions of the tyrosinase gene were amplified
      by polymerase chain reaction (PCR) and were directly sequenced in both
      directions. RESULTS: We successfully amplified all exons of the tyrosinase gene
      by PCR and were able to characterize compound heterozygous mutations of R278X and
      + delta C310 in the patient's gene. CONCLUSION: Recent advances of PCR-related
      technology allowed us to use fairly limited samples of blood for sequence
      analysis of the tyrosinase gene.

PMID- 9568406
TI  - Superantigen production by Staphylococcus aureus in psoriasis.
AB  - BACKGROUND: Activation of T cells is believed to play a critical role in the
      pathogenesis of psoriasis. Recently, it has been proposed that psoriasis is a T
      cell-mediated autoimmune reaction triggered by bacterial superantigen. OBJECTIVE:
      We investigated whether patients with chronic plaque psoriasis bear superantigen
      producing Staphylococcus aureus on the skin or the throat. METHODS: S. aureus
      producing exfoliative toxin, staphylococcal enterotoxin B or toxic shock syndrome
      toxin 1 was isolated from the skin and throat of 100 psoriasis patients using
      Western blot analysis and polymerase chain reaction. RESULTS: Only 5, 4 and 9
      patients had super-antigen producing S. aureus identified on lesional skin,
      nonlesional skin and throat, respectively. The vast majority of patients did not
      bear superantigen-producing S. aureus. CONCLUSION: We believe that superantigens
      are not essential in sustaining disease activity but may, instead, be
      exacerbating or triggering factors for some psoriasis patients.

PMID- 9568408
TI  - Life span of skin fibroblasts in patients with systemic sclerosis.
AB  - BACKGROUND: It remains unknown whether the life span of systemic sclerosis (SSc)
      skin fibroblasts (FB) and that of normals are the same or not, though SSc skin FB
      have been shown to present abnormalities such as elevated collagen synthesis.
      OBJECTIVE: To find out whether the life span of SSc skin FB and that of normals
      are the same or not. METHODS: Cell generation and colony-forming efficiency were
      calculated in 10 normal and 7 SSc FB, and total life spans were studied. RESULTS:
      Colony-forming efficiency decreased from 30 to 5% until the cells reached
      senescence. The cell generations of normal and SSc FB showed no significant
      difference. CONCLUSION: SSc FB is senescent and may indicate that the senescence
      of SSc FB is independent of its abnormal features.

PMID- 9568407
TI  - Epiluminescence microscopy versus clinical evaluation of pigmented skin lesions:
      effects of Operator's training on reproducibility and accuracy. Dermatology and
      Venereology Society of the Canton of Ticino.
AB  - BACKGROUND: An acceptable level of reliability is a prerequisite for the
      introduction of epiluminescence microscopy (ELM) into the diagnosis of pigmented
      skin lesions. OBJECTIVE: To assess the effects of a training program on the
      reproducibility and accuracy of ELM as compared to clinical evaluation. METHODS:
      Before and after the program, 48 clinical images and their ELM counterparts were
      independently evaluated by seven participants. Reproducibility was measured by
      the kappa index, accuracy by the rate of exact diagnoses (RED) assuming histology
      as a reference. RESULTS: We observed (i) no effect of training on clinical
      reproducibility, (II) an improved reproducibility of ELM diagnoses of non
      melanocytic lesions (NML) and melanomas but not of melanocytic nevi (MN), (iii) a
      greater increase in the clinical RED of NML and melanomas compared with MN and
      (iv) a similar though more pronounced increase in the RED on ELM. CONCLUSIONS:
      The effects of training were greater for ELM as compared to clinical diagnosis,
      and for NML and melanomas as compared to MN.

PMID- 9568409
TI  - Merkel cells in hyperplastic and neoplastic lesions of the skin. An
      immunohistochemical study using an antibody to keratin 20.
AB  - BACKGROUND: Merkel cells are neuro-endocrine cells present in the basal layer of
      the human epidermis and the outer root sheath of hair follicles. OBJECTIVE AND
      METHOD: In order to gain further insight into the as yet ill-defined involvement
      of Merkel cells in skin diseases, we studied the distribution of these cells in
      formalin-fixed, paraffin-embedded sections of 165 inflammatory, hyperplastic or
      tumoral skin lesions of various anatomic locations, with a monoclonal antibody to
      keratin 20. RESULTS: Lesions with frequently increased Merkel Cell numbers
      included actinic keratosis, fibrous papules of the face and some conditions with
      (immature) hair follicle differentiation. CONCLUSION: These results suggest that
      Merkel cell hyperplasia is unrelated to epidermal proliferation but that it is
      rather specific to a limited number of skin diseases.

PMID- 9568410
TI  - A case of unique subepidermal blistering disease with autoantibodies against a
      novel dermal 200-kD antigen.
AB  - BACKGROUND: Several autoimmune subepidermal blistering diseases with
      autoantibodies against the epidermal basement membrane zone (BMZ) have been
      identified. Each shows distinct immunological findings. OBJECTIVES: Our patient
      showed clinical features which were indicative of bullous pemphigoid or linear
      IgA bullous dermatosis. In his serum, circulating IgG antibodies binding to the
      dermal side of skin split with 1 M NaCl were detected. To clarify the
      immunological character of the patient, we performed further studies. METHODS:
      Western immunoblot analysis using normal human skin extracts and indirect
      immunofluorescence (IF) with affinity-purified IgG antibodies to the detected
      dermal protein were done. RESULTS: Western immunoblot analysis demonstrated IgG
      antibodies reacting with a dermal 200-kD protein. Affinity-purified IgG
      antibodies to the 200-kD protein reacted to the dermal side of the split by
      indirect IF. Therefore, this dermal 200-kD protein is believed to be the
      epidermal BMZ antigen. CONCLUSION: Our patient showed an immunologically unique
      subepidermal blistering disease.

PMID- 9568411
TI  - Efficacy of urea therapy in children with ichthyosis. A multicenter randomized,
      placebo-controlled, double-blind, semilateral study.
AB  - BACKGROUND: Ichthyoses are genetic disorders of keratinization which are
      uncomfortable due to their conspicuous scaling, itching and cosmetic problems.
      Especially in childhood, ichthyoses can lead to social discrimination and
      psychological problems. Efficient therapies are necessary which are safe and well
      tolerated. OBJECTIVE: The aim of the study was to investigate the keratolytic and
      moisturizing properties as well as the tolerance of a new urea lotion when
      applied to hyperkeratotic and ichthyotic skin in childhood. METHODS: The study
      was conducted as a multicenter, randomized, placebo-controlled, double-blind,
      semilateral investigation. Sixty children between 1 and 16 years treated one side
      of the most affected extremity with Laceran 10% urea lotion for 8 weeks. On the
      other side the urea-free Laceran lotion base was given. On each side of the body
      a control area was left untreated. The investigators evaluated the global
      severity of ichthyotic symptoms with the help of a visual analogue scale.
      RESULTS: The analysis of the global estimation of severity of ichthyosis showed
      improvements being stronger in the body areas treated with Laceran 10% urea
      lotion (from 4.8 to 2.0 points) than in the areas treated with the urea-free
      Laceran lotion base (from 4.8 to 2.5 points). The response rates were 65% after 4
      weeks and 78% after 8 weeks for Laceran 10% urea lotion, 50% after 4 weeks and
      72% after 8 weeks for the urea-free Laceran lotion base. CONCLUSION: It can be
      ascertained that Laceran 10% urea lotion has a strong positive effect on
      generalized ichthyotic keratinization disorders.

PMID- 9568412
TI  - Fumaric acid esters suppress peripheral CD4- and CD8-positive lymphocytes in
      psoriasis.
AB  - BACKGROUND: For severe forms of psoriasis vulgaris, the antipsoriatic fumaric
      acid esters (FAE) therapy has recently gained increasing acceptance and
      importance. Until today, there is little knowledge about the mode of action of
      FAE. However, some evidence exists indicating immunosuppressive effects.
      OBJECTIVE: The aim of this study was to examine the systemic, particularly the
      immunological changes in patients suffering from psoriasis treated with FAE over
      a long period of time, since we expect to see pharmacological effects of FAE at
      this point. METHODS: This study is based on continuously recorded clinical data
      and laboratory parameters of 10 patients, who were treated over a period of 12
      months with FAE. A quantitative analysis of lymphocytes and their subtypes was
      carried out by means of flowcytometric methods. RESULTS: 3 months after starting
      treatment with FAE, a clinical effect with a remission index > 95% was achieved
      in all 10 patients examined. This remained constant until the end of this study.
      Focusing on leukopenia, and particularly on lymphopenia as important parameters,
      these effects were found in all patients. The lymphocyte subpopulations data
      demonstrated extensive proportionate reductions. Within the T cell fraction a
      stronger suppression of CD8+ lymphocytes was observed. CONCLUSION: Our
      investigations of systemic effects of fumaric acid esters demonstrate the
      suppressive character of this medication. Effects of cell count reduction in
      leukocyte and lymphocyte numbers over the entire period of 12 months could be
      observed. The lymphocytic cell count number is obviously linked to the clinical
      effect.

PMID- 9568413
TI  - Conversion of psoriasis patients from the conventional formulation of cyclosporin
      A to a new microemulsion formulation: a randomized, open, multicentre assessment
      of safety and tolerability.
AB  - OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A
      (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with
      severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS:
      In this 24-week, open, randomized, prospective, multicentre trial, 28 patients
      continued on the same dosage of SIM, while 30 converted to Neoral at 2.5
      mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the
      study, dosages could be adjusted to maintain efficacy, because of adverse events
      or after disease stabilization. The maximum permitted dosage for either
      formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis
      Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The
      dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and
      20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups,
      PASI scores remained stable throughout and relapses were primarily a result of
      dosage reduction after disease stabilization. No significant difference was found
      between groups in the proportion of patients remaining relapse-free. Adverse
      events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most
      drug-related events were of mild or moderate severity and reflected the known CyA
      side-effect profile. Dose titration guidelines ensured that mean blood pressure
      and serum creatinine concentrations remained stable in both groups. CONCLUSIONS:
      If the guidelines for CyA use are followed and the Neoral dosage does not exceed
      5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to
      Neoral should present no clinically relevant safety or tolerability problems and
      efficacy of treatment is maintained.

PMID- 9568414
TI  - Fluconazole in the treatment of tinea corporis and tinea cruris.
AB  - BACKGROUND: Results of topical dermatomycosis treatment are often unsatisfactory,
      particularly in patients with extended or multiple infection sites. OBJECTIVE:
      Given the high fluconazole concentrations attainable in the stratum corneum and
      the long elimination half-life of fluconazole, we investigated whether efficacy
      is satisfactory when using fluconazole at once weekly doses of 150 mg. METHODS:
      In an open, noncomparative study, tinea corporis and cruris patients were treated
      with once weekly fluconazole 150 mg over 2-4 weeks. Clinical (pruritus, erythema,
      scaling, burning/pain, vesiculation) and mycologic (culture and microscopy)
      assessments were performed before treatment, at weekly intervals until the end of
      treatment and 3 weeks after treatment. All adverse events were recorded. RESULTS:
      The total severity scores of clinical symptoms were reduced from 7.1 before to
      1.5 after treatment (p = 0.001, n = 100 patients). Seven patients experienced
      adverse events. CONCLUSIONS: Fluconazole 150 mg once weekly for 2-4 weeks is an
      efficacious and safe regimen in the treatment of tinea corporis and cruris.

PMID- 9568415
TI  - Eccrine syringofibroadenoma: report of a case and analysis of cytokeratin
      expression.
AB  - Eccrine syringofibroadenoma (ESFA) is a rare disorder which shows differentiation
      toward the eccrine sweat apparatus. There is a controversy concerning the
      pathogenesis and precise differentiation of this tumor. We report a case of ESFA
      and its differentiation pattern by an analysis of cytokeratin expression. Using
      paraffin-embedded materials, histopathological and immunohistochemical studies
      were performed. Staining patterns of the luminal, peripheral, and inner cells of
      the tumor strands closely matched or mimicked those of the luminal, outer and
      intermediate cells of the normal eccrine dermal duct, respectively. The case of
      ESFA reported revealed a pattern of differentiation suggestive of an eccrine duct
      origin.

PMID- 9568416
TI  - Primary cutaneous Nocardia asteroides infection after heart transplantation.
AB  - Skin diseases due to Nocardia are rare in Europe and usually occur as the
      secondary localization of a pulmonary lesion in immunocompromised patients. We
      describe a cutaneous pyoderma and cold abscess due to Nocardia asteroides
      infection in a cardiac transplant recipient. An insect bite represents the wound
      of this soil saprophyte belonging to the actinomycetes. Treatment by sulfone and
      ampicillin-clavulanic acid allowed the regression of lesions without
      extracutaneous dissemination.

PMID- 9568417
TI  - An unusual hypopigmentation in occupational dermatology: presentation of a case
      and review of the literature.
AB  - Contact dermatitis to cooling lubricants is commonly encountered in occupational
      dermatology, but it rarely induces pigmentary skin changes. It is sometimes
      difficult to differentiate between toxic leukoderma and postinflammatory
      hypopigmentation when examining a depigmentation. A differential diagnosis is
      described in the case of a 31-year-old metal worker, spending most of his time on
      a computer-numerically controlled machine, who presented with cumulative irritant
      hand dermatitis and secondary hypopigmentation. Patch tests gave negative
      reactions to the European standard series, the disinfection and preservative
      series, the base preparation and emollient series, the metal series, the
      mechanical worker series as well as to the cooling lubricant itself. Atopy
      screening was positive for a variety of pollens. Based on biopsy findings, toxic
      leukoderma could be diagnosed even though none of the known melanotoxic compounds
      could be identified in his work environment. The patient was advised to avoid
      further contact with the regular composed cooling lubricant and the contact
      eczema improved dramatically, whereas the condition of hypopigmentation got
      better slowly within weeks under PUVA therapy.

PMID- 9568418
TI  - Polythelia within Becker's naevus.
AB  - We report a case of accessory mammary tissue of type 2a (or polythelia) entirely
      localized within a Becker's naevus of mixed type in a 32-year-old Caucasian
      woman. Polythelia was congenital in origin while Becker's naevus appeared during
      puberty. Renal ultrasonographic studies, laboratory examinations and other
      instrumental investigations were either normal or negative. Although the
      association of accessory mammary tissue with Becker's naevus has previously been
      reported--also in the form of mammorenal and acromammorenal syndromes--this is
      the first case characterized by an anatomic overlap between the two anomalies. It
      may be the expression of a common disturbance acting early in embryogenesis in
      the specific developmental fields involved.

PMID- 9568419
TI  - Exfoliative cheilitis: a case report and review of the literature.
AB  - We examined a 16-year-old male with persistent crusting of the lips. Biopsy
      showed parakeratosis, which is a normal feature, and a mild inflammatory
      infiltrate without fungal infection. These findings are compatible with a
      diagnosis of exfoliative cheilitis. Medication with anti-depressants was helpful.
      To date, the condition has been reported under various names: factitious
      cheilitis, localized crusting as an artifact, factitious lip crusting, and
      exfoliative cheilitis, because some cases are thought to be factitious. We
      suggest to call this condition 'factitious type' or 'idiopathic type' of
      exfoliative cheilitis, respectively, independent of the presence of a psychiatric
      problem.

PMID- 9568420
TI  - Ulcerative porokeratosis.
AB  - A 54-year-old man presented with multiple annular plaques since infancy. During
      the intake of nifedipine and nitroglycerin over a period of 6 years, reddish,
      eruptive and ulcerative changes were seen in the pre-existing skin lesions on the
      penis, scrotum and legs. In addition to a typical cornoid lamella, histological
      examination revealed a band-like infiltration beneath the epidermis, liquefaction
      degeneration of the basal cell layer and subsequent coagulative necrosis of the
      keratinocytes. We review similar ulcerative types of porokeratosis in the
      literature and discuss the significance of our unusual case.

PMID- 9568421
TI  - A female patient with the Rothmund-Thomson syndrome associated with anhidrosis
      and severe infections of the respiratory tract.
AB  - The Rothmund-Thomson syndrome is a rare syndrome which is believed to be
      inherited in an autosomal pattern. Poikiloderma of the face and extremities is a
      characteristic feature. Besides this, less common aspects have been reported like
      alopecia, cataracts, short stature, musculoskeletal/bone defects or small hands,
      hypogonadism, abnormal teeth, dysplastic nails, anhidrosis and a high incidence
      of cutaneous and non-cutaneous malignancies. We present a patient with the
      Rothmund-Thomson syndrome together with anhidrosis and multiple infections of the
      upper and lower respiratory tract. Investigation of immunological function
      revealed a low total number of T lymphocytes with a slightly depressed
      reactivity. Immunoglobulins were markedly increased.

PMID- 9568422
TI  - Skin necrosis at the injection site induced by low-molecular-weight heparin: case
      report and review.
AB  - Heparin-induced skin necrosis at the injection site is a rare adverse effect,
      more commonly associated with standard heparins than with low-molecular-weight
      heparins (LMWH) and its mechanism remains unclear. We report a case of LMWH
      induced skin necrosis in a female during prophylactic treatment with LMWH after a
      surgical procedure. Determination of heparin-platelet-factor-4(PF4)-induced
      antibodies was positive. This case describes the occurrence of LMWH-induced skin
      necrosis and antibodies to heparin-PF4 complex, suggesting that this effect is
      more frequent than previously suspected.

PMID- 9568424
TI  - Linear lichen planus in the region of the mandibular nerve caused by an allergy
      to palladium in dental metals.
AB  - We observed a case of linear lichen planus extending from the right cheek to the
      jaw, which was accompanied by itching and an unusual sensation in the mouth. The
      eruption was located along the mandible and aligned with the mandibular nerve.
      The right molars of the patient contained metal compounds and these were
      considered to be the cause of his disease. Patch testing with various dental
      metals showed positive reactions to palladium and platinum. A biopsy specimen
      showed a lichenoid reaction in the lesional tissue, and dermal contact dermatitis
      was noted at the palladium patch test site. His dentist reported that palladium
      silver-gold or nickel-chrome alloys without platinum had been used in the crown
      and bridge of his molars. After removal of the dental alloys, the skin eruption
      resolved with some residual hyperpigmentation. In addition, the peculiar mouth
      sensation disappeared dramatically within 2 months.

PMID- 9568423
TI  - Interaction between terbinafine and warfarin.
AB  - A 71-year-old woman presented with gastrointestinal bleeding. She had been
      stabilized on warfarin for the previous few months. Terbinafine had been started
      32 days prior to this episode for the treatment of onychomycosis. The patient had
      been on cimetidine for the previous 2 years and on other medications for the last
      10 years. At the time of admission for the gastrointestinal bleeding, the
      coagulation indices were all above the therapeutic range. Endoscopy of the
      gastrointestinal tract exhibited diffuse intestinal 'oozing' consistent with
      coagulopathy as the cause of bleeding. Terbinafine may have had an effect on the
      metabolism of warfarin since both are metabolized through the liver and
      cimetidine can reduce terbinafine clearance by 33% resulting in higher
      concentrations of the antifungal agent. Our experience suggests that caution
      should be exercised when prescribing terbinafine to a patient receiving warfarin.

PMID- 9568426
TI  - Conjugal leprosy among Libyan patients.

PMID- 9568425
TI  - Acute generalized exanthematous pustulosis due to the combination of chloroquine
      and proguanil.

PMID- 9568427
TI  - Truncal telangiectases coinciding with felodipine.

PMID- 9568428
TI  - Multiple actinic keratosis and skin tumors secondary to hydroxyurea treatment.

PMID- 9568429
TI  - Not all black follicular plugs are comedones!

PMID- 9568430
TI  - Pityriasis rosea and human herpesvirus 7, a true association?

PMID- 9568432
TI  - Myocyte apoptosis and heart failure.

PMID- 9568433
TI  - Mortality in winter.

PMID- 9568434
TI  - Exercise training in chronic heart failure: the European experience.

PMID- 9568435
TI  - Factors leading to progression of atherosclerotic coronary artery disease in
      young males following a first myocardial infarction.

PMID- 9568436
TI  - Chronic infection and atherogenesis.

PMID- 9568437
TI  - Cardioprotection by pre-infarct angina: is it ischaemic preconditioning?

PMID- 9568438
TI  - Target doses of ACE inhibitors in heart failure: where should we aim?

PMID- 9568439
TI  - Diagnosis and investigation of essential and secondary hypertension.

PMID- 9568440
TI  - Survival analysis and classification of death in patients under anti-arrhythmic
      treatment.

PMID- 9568441
TI  - The long-term management of the patient with an aortic coarctation repair.

PMID- 9568442
TI  - Association between antibodies to heat shock protein 65 and coronary
      atherosclerosis. Possible mechanism of action of Helicobacter pylori and other
      bacterial infections in increasing cardiovascular risk.
AB  - INTRODUCTION: There is growing evidence that the immune response is involved in
      atherosclerosis. Antibodies to heat shock protein 60/65 have been shown to be a
      risk factor for carotid atherosclerosis and been proposed as a diagnostic marker
      of atherosclerosis. In addition, it has been suggested that the immune response
      to heat shock protein 60/65 may be a link between exposure to microorganisms and
      increased cardiovascular risk. AIMS: (1) To investigate the association between
      anti-shock protein 65 titre and coronary atherosclerosis. (2) To assess whether
      anti-mhsp65 titre is a useful diagnostic marker of atherosclerosis; (3) To
      examine the influence of Helicobacter pylori infection on anti-heat shock protein
      65 titre. METHODS AND RESULTS: In the first study we measured anti-heat shock
      protein 65 titres in 136 consecutive male subjects admitted for routine coronary
      angiography. Anti-heat shock protein 65 titres correlated with both the severity
      and extent of coronary atherosclerosis and the relationship remains statistically
      significant for the presence of atherosclerosis (P = 0.012) after adjustment for
      possible confounding influences. However the association had insufficient
      sensitivity to be a useful clinical test. In the second study we recruited 100
      patients with confirmed active H. pylori infection and double blindly randomized
      them to eradication therapy or placebo. Successful eradication of H. pylori led
      to a significant fall in anti-heat shock protein 65 titres (from a mean of 256.4
      AU.ml-1 to 137.5 AU. ml-1. P = 0.033). CONCLUSION: These results raise the
      possibility that exposure to H. pylori and other micro-organisms lead to an
      increased risk of clinically manifest coronary artery disease by an autoimmune
      process.

PMID- 9568443
TI  - High incidence of dyslipidaemia in the offspring of Greek men with premature
      coronary artery disease.
AB  - AIM: The present study aimed to assess the incidence and type of lipid disorders
      in the offspring of young Greek coronary patients. METHODS: One hundred and
      ninety-three children and youngsters were divided into two groups. Group A
      consisted of 104 children whose fathers had sustained a myocardial infarction
      before the age of 55 years. Eighty-nine young subjects matched for age, gender,
      dietary and smoking habits without a familial history of coronary artery disease
      served as controls (group B). Total cholesterol, triglycerides, high density
      lipoprotein cholesterol, low density lipoprotein cholesterol and lipoprotein(a)
      were measured in the children and the affected fathers. RESULTS: Fifty-three
      percent of the offspring of young coronary patients had elevated total
      cholesterol or elevated triglycerides or decreased high density lipoprotein
      cholesterol or a combination, while the 80.4% of the affected fathers had lipid
      disorders. The distribution of lipid disorders in the children bore a striking
      resemblance to those seen in their affected fathers and there was a significant
      correlation between offspring-father total cholesterol, low density lipoprotein
      cholesterol and lipoprotein(a). When excess lipoprotein(a) was added to the lipid
      disorders the incidence of dyslipidaemia in the offspring of the affected
      individuals was increased to 63.5%. CONCLUSIONS: Dyslipidaemia is very common in
      the offspring of Greek men with premature coronary artery disease; this
      occurrence emphasizes the need always to evaluate the lipid profile in these
      children. The detection of dyslipidaemia necessitates the early institution of
      preventive measures with the expectation that the incidence of cardiovascular
      disease will decrease later in life.

PMID- 9568444
TI  - Progression of coronary artery disease in young male post-infarction patients is
      linked to disturbances of carbohydrate and lipoprotein metabolism and to impaired
      fibrinolytic function.
AB  - AIMS: To assess determinants of coronary artery disease progression in men with
      previous myocardial infarction. METHODS AND RESULTS: A total of 102 unselected
      non-diabetic Swedish men (age 40.4 +/- 3.6, range 23-44 years) entered the study
      3-6 months after a first myocardial infarction. The programme included metabolic
      and haemostatic investigations and routine coronary angiography at baseline,
      followed by re-angiography 5 years later. Of the original cohort, 76 patients
      underwent a second angiogram. Separate semiquantitative scoring systems were used
      for diffuse coronary atherosclerosis and distinct stenoses in 15 proximal
      coronary segments. Smoking, global severity of coronary atherosclerosis and
      presence of multi-vessel disease at baseline (P < 0.001) characterized patients
      with severe progression of both diffuse and focal lesions. Higher plasma levels
      of low density lipoprotein cholesterol (P < 0.01) and low density lipoprotein
      triglycerides (P < 0.05), a lower plasma high density lipoprotein2 cholesterol
      level (P < 0.05) and higher plasma plasminogen activator inhibitor-1 activity (P
      < 0.05), together with a high baseline stenosis score (P < 0.001) characterized
      patients with severe progression of coronary atherosclerosis. On the other hand,
      more pronounced fasting and post-prandial glycaemia (P < 0.05), together with
      higher plasma plasminogen activator inhibitor-1 activity (P < 0.01) characterized
      severe progressors with respect to coronary stenosis. Multivariate analysis
      identified the presence of multi-vessel disease as an independent predictor of
      progression of both coronary atherosclerosis (P = 0.008) and stenoses (P =
      0.007), whereas a high low density lipoprotein triglyceride level (P < 0.01) was
      independently related to progression of coronary atherosclerosis and a high
      fasting glucose level (P = 0.02) to progression of coronary stenoses. CONCLUSION:
      Disturbances in carbohydrate and lipoprotein metabolism and impaired fibrinolytic
      function are associated with progression of coronary artery disease in young male
      post-infarction patients.

PMID- 9568445
TI  - New-onset angina preceding acute myocardial infarction is associated with
      improved contractile recovery after thrombolysis.
AB  - BACKGROUND: Ischaemic preconditioning reduces myocardial infarct size in animal
      models. Clinical data suggest that episodes of angina immediately before acute
      myocardial infarction may be associated with smaller infarct size in man.
      However, it is unclear whether ischaemic episodes preceding acute myocardial
      infarction also affect contractile recovery in patients. OBJECTIVE: In this study
      we investigated the recovery of regional myocardial function after thrombolysis
      in two groups of patients at their first Q-wave acute myocardial infarction; in
      one group (n = 42) myocardial infarction occurred unheralded, whereas patients of
      the second group (n = 48) had experienced new-onset angina in the 48 h that
      preceded infarction. Echocardiographic analysis of myocardial regional function
      in the infarct area was done at 2, 24 and 72 h after thrombolysis, and at 1 week,
      and 1 and 3 months follow-up. RESULTS: Peak level of MB-creatine kinase was
      significantly lower in patients with new-onset angina (96 +/- 47 as compared with
      221 +/- 108 IU.l-1, P < 0.01), as was the area under the MB-creatine kinase curve
      (1321 +/- 876 as compared to 3879 +/- 1555 U.l-1/36 h, P < 0.01). Hypokinetic
      segments were fewer in patients with pre-infarction angina. Similarly, wall
      motion score improved significantly earlier in patients who had new-onset angina
      before acute myocardial infarction. Thus, contractile recovery was more rapid in
      patients with previous angina than in those in whom infarction occurred
      unheralded. Complications during the in-hospital outcome and other variables
      considered during the 4-week follow-up were similar between groups. CONCLUSIONS:
      Patients who experienced new-onset angina before acute myocardial infarction
      showed better recovery of regional function after thrombolysis. Our study
      supports the hypothesis that brief periods of ischaemia immediately before
      myocardial infarction may precondition the human heart, thus improving
      contractile recovery.

PMID- 9568446
TI  - Exercise-induced T-wave normalization predicts recovery of regional contractile
      function after anterior myocardial infarction.
AB  - AIMS: We investigated the ability of T-wave pseudonormalization and ST-segment
      elevation, which are demonstrated in infarct-related leads during submaximal
      exercise testing, to predict late recovery of contractile function. METHODS: We
      studied 88 consecutive patients (73 males, mean age 59 +/- 8 years) with anterior
      infarction, persistent T-wave inversion and a documented lesion of the proximal
      segment of the left anterior descending coronary artery. They all underwent 2D
      echocardiography on admission, 4 weeks as well as 6 months after myocardial
      infarction to evaluate the dysfunction score and the ejection fraction.
      Submaximal (75% of maximal predicted heart rate) exercise testing was performed
      in 80 patients 2 weeks after myocardial infarction following discontinuation of
      treatment. RESULTS: During exercise testing, 59 of the 88 patients showing
      negative T-waves on the resting electrocardiogram exhibited pseudonormalization
      (group A) in at least three adjacent precordial leads, whilst 29 (group B) did
      not. Patients of group A more frequently exhibited an early creatine kinase peak
      (41% vs 24%, P < 0.05) and residual angiographic perfusion (97% vs 69%, P <
      0.05). The dysfunction score did not change in group B (from 19 +/- 7 to 22 +/-
      4), but decreased in group A (from 18 +/- 4 to 11 +/- 6 P < 0.05). The ejection
      fraction was similar in the two groups on admission (group A: 48 +/- 7%, group B:
      45 +/- 10%), but was significantly different at 4-week (52 +/- 99 vs 42 +/- 11%,
      P < 0.05) and 6-month follow-up (58 +/- 9 vs 44 +/- 10%, P < 0.01). The
      concomitant presence of ST-segment elevation and T-wave normalization showed the
      highest positive predictive value for left ventricular function recovery (100%).
      CONCLUSIONS: T-wave normalization induced by submaximal exercise test is
      frequently associated with residual perfusion to the infarct area and predicts
      progressive improvement in regional wall motion, especially if associated with ST
      segment elevation. Therefore, these electrocardiographic findings may be used as
      easily obtainable markers of residual viability that predict late recovery in
      contractile function.

PMID- 9568447
TI  - The incidence of suspected myocardial infarction in Dutch general practice in the
      period 1978-1994.
AB  - AIM: To evaluate how the incidence of suspected myocardial infarction has
      developed from 1978 to 1994 and to study the incidence of confirmed acute
      myocardial infarction in Dutch general practices during the period 1991-1994.
      METHODS: In three periods (1978, 1983-1985 and 1991-1994) the incidence of
      suspected myocardial infarction has been registered by the 'Dutch Sentinel
      Practice Network'. This is a registration system that obtains data from general
      practitioners covering about 150,000 persons. During the period 1991-1994 the
      incidence of confirmed myocardial infarction was also registered. RESULTS: For
      men, the incidence rate of suspected myocardial infarction decreased by 28% from
      4.7 per 1000 in 1978 to 3.4 per 1000 in the period 1991-1994. For women, the
      incidence fell by 23% from 2.6 per 1000 in 1978 to 2.0 per 1000 in the period
      1983-1985 and stabilized thereafter. The most pronounced decrease in the
      incidence of suspected myocardial infarction during the period 1978-1994 occurred
      in both men and women aged 45-64. In the period 1991-1994, the standardized
      incidence rate of confirmed myocardial infarction is 1.7 per 1000 for men and 0.9
      per 1000 for women. CONCLUSIONS: These data suggest that the incidence of
      suspected myocardial infarction has declined substantially between 1978 and 1994
      both for men and for women; this decline is most pronounced in the age group 45
      64.

PMID- 9568448
TI  - Single-beat analysis of ventricular late potentials in the surface
      electrocardiogram using the spectrotemporal pattern recognition algorithm in
      patients with coronary artery disease.
AB  - AIMS: Post-infarction risk stratification can be ascertained from beat-to-beat
      variations in ventricular late potentials. However, gaining such information by
      conventional late potential analysis using signal averaging is still not
      possible. METHODS: We therefore developed the spectrotemporal pattern recognition
      algorithm in order to detect beat-to-beat variations in late potentials. Based on
      the spectrotemporal pattern recognition algorithm two-dimensional correlation
      function, the typical spectral pattern of late potentials can be identified in
      spectrotemporal maps of single beats, even in the presence of noise. RESULTS:
      Surface electrocardiograms of 385 patients after myocardial infarction (85 with
      documented sustained ventricular tachycardia (group 1), 100 with fast,
      polymorphic ventricular tachycardia (> 270 cycles.min-1) or primary ventricular
      fibrillation (group 2), 200 without ventricular arrhythmias (group 3) and 45
      healthy volunteers (group 4), were analysed. The spectrotemporal pattern
      recognition algorithm detected late potentials in single beats in 89% of group 1
      patients, in 79% of group 2, in 22% of group 3 and in 4% of normals. The
      spectrotemporal pattern recognition algorithm measured late potential frequency
      and extension of late potentials into the ST segment, which was significantly
      different between groups 1 and 2. Beat-to-beat variations in late potentials,
      with respect to frequency and extension into the ST segment, were markedly higher
      in patients with a history of primary ventricular fibrillation. CONCLUSION:
      Single-beat analysis using the spectrotemporal pattern recognition algorithm may
      improve risk stratification of patients after myocardial infarction, and provides
      information on patients prone to ventricular fibrillation.

PMID- 9568449
TI  - Long-term clinical outcome following coronary artery bypass grafting for isolated
      stenosis of the left anterior descending coronary artery.
AB  - AIMS: To detail the clinical and angiographic profile, and long-term outcome in
      consecutive patients with isolated stenosis of the left anterior descending
      coronary artery undergoing bypass surgery. METHODS: A retrospective study of all
      patients (n = 301) (January 1984-December 1990) and undergoing coronary artery
      bypass grafting for isolated left anterior descending disease, in the Irish
      Republic, was performed. Survival was compared with that of an exact age- and
      gender-matched cohort. RESULTS: Mean age was 53 (+/- 9.3) years. There were 238
      (79%) males. In 241 (80%) patients an internal thoracic arterial bypass graft was
      used. Operative mortality was 1.3%. Of the 280 (93%) patients alive (16 cardiac
      deaths) at 7.1 (+/- 1.9) years, 105 (35%) had angina, 26 (9%) suffered an
      interval myocardial infarction, and repeat revascularization was required on 29
      (10%). Female gender (P = 0.002), pre-operative myocardial infarction (P = 0.02),
      significant diagonal disease (P = 0.04) and postoperative myocardial infarction
      (P = 0.0001) were independently associated with survival. Females were more
      likely to develop congestive cardiac failure (P = 0.01) or postoperative angina
      (P = 0.03) than their male counterparts. CONCLUSIONS: Survivorship (97%) and
      event-free survival (96%) at 5 years following coronary artery bypass grafting
      for isolated left anterior descending coronary artery disease is excellent and
      equivalent to an age-matched and gender-matched cohort.

PMID- 9568450
TI  - Complications of intra-aortic balloon counterpulsation. The role of catheter size
      and duration of support in a multivariate analysis of risk.
AB  - AIMS: The aim of this study was to assess the risk of intra-aortic balloon
      counterpulsation and to identify clinical and procedural variables that would
      predict complications. METHODS AND RESULTS: We analysed 381 consecutive patients
      who were treated between 1977 and 1995 at our catheterization laboratory and/or
      medical intensive care unit. The complications considered relevant were limb
      ischaemia requiring catheter removal, vascular injury, bleeding requiring
      transfusion, embolic events, and infection. In eight patients the balloon could
      not be inserted. The rate of complications for the remaining 373 patients was
      12.9%. Between 1977 and 1980, surgical insertion was performed using a 12 French
      catheter with a complication rate of 30.4% (seven of 23 patients). Percutaneous
      implantation, performed after 1981, had an overall complication rate of 11.7% (41
      of 350 patients). Using thinner catheters for percutaneous placement was
      associated with a reduction in the rate of complications, from 20.7% (17 of 82
      patients) for 12 French catheters to 9.9% (10 of 101 patients) for 10.5 French
      catheters (P = 0.04), and 8.4% (14 of 167 patients) for 9.5 French catheters (P =
      0.006). Multivariate logistic regression analysis identified duration of
      counterpulsation > 48 h (odds ratio 3.6), catheter size (odds ratio 3.4 for 12
      French catheters), peripheral vascular disease (odds ratio 2.7), and shock (odds
      ratio 2.0) as independent risk factors for counterpulsation-associated
      complications. When considering 9.5 French catheters only (167 patients, all
      after 1992), the sole remaining independent risk factor was duration of
      counterpulsation > 48 h (odds ratio 3.8). Those patients with 9.5 French
      catheters in whom counterpulsation did not exceed 48 h had a low complication
      rate of 3.9%. CONCLUSION: The rate of percutaneous intra-aortic balloon
      counterpulsation complications was thus significantly reduced by employing
      thinner catheters. It was at an acceptable level for 9.5 French catheters, where
      a long duration of counterpulsation emerged as the most significant factor
      associated with complications. Whether using even thinner catheters in
      combination with a sheathless implantation technique further minimizes the risk
      of counterpulsation remains to be seen.

PMID- 9568451
TI  - Experience from controlled trials of physical training in chronic heart failure.
      Protocol and patient factors in effectiveness in the improvement in exercise
      tolerance. European Heart Failure Training Group.
AB  - BACKGROUND: Beneficial effects of physical training on exercise tolerance,
      autonomic and skeletal muscle function and limb blood flow have been demonstrated
      in chronic heart failure. Because this rehabilitation is expensive, may involve
      risk, and has unknown effects on prognosis, the possibility of predicting benefit
      on the basis of individual patient data is intriguing. The most suitable exercise
      training programme has not yet been established. METHODS AND RESULTS: We reviewed
      the progress of 134 stable heart failure patients studied in randomized
      controlled trials of physical training. A significant training effect (+13% peak
      oxygen consumption, +17% exercise duration) was associated with improved
      autonomic indices (resting catecholamines and hormones, heart rate variability),
      without significant side-effects. No ventilatory, haemodynamic, autonomic or
      clinical factor at baseline was a predictor of outcome. Similar beneficial
      effects were observed in both male and female patients. The improvement in oxygen
      consumption after 16 weeks training was higher than after 6 weeks (+2.6 +/- 3.0
      vs +0.3 +/- 3.1 ml.kg.min-1, P < 0.05). The combination of cycle ergometer with
      calisthenic exercises was more beneficial than cycle ergometer alone (+2.7 +/-
      4.2 vs 1.2 +/- 2.0 ml.kg.min-1, P < 0.01). The presence of nonsustained
      ventricular tachycardia did not preclude a training effect. Patients older than
      70 years were able to train, although less effectively than the younger ones. No
      difference in exercise gain was observed whether the patients trained in the
      hospital or at home. CONCLUSION: The positive effects of physical rehabilitation
      in chronic stable heart failure patients are confirmed. No baseline patient
      factor was significantly correlated with outcome. A tailored, moderate, home
      based, combined cycle ergometer, plus calisthenic exercise training seems safe
      and beneficial in a large cohort of heart failure patients, with similar benefits
      in a variety of conditions and different hospital settings.

PMID- 9568452
TI  - Endogenous insulin and insulin sensitivity. An important determinant of skeletal
      muscle blood flow in chronic heart failure?
AB  - AIM: Patients with heart failure have a reduced sensitivity to insulin's actions
      on glucose metabolism and a compensatory increase in endogenous plasma insulin
      levels. As insulin has a selective vasodilatory action in skeletal muscle, we
      have studied the association between insulin sensitivity and central and regional
      haemodynamics in patients with heart failure. METHODS: Ten patients with stable
      symptomatic heart failure were studied. We used non-invasive techniques to
      measure cardiac output, forearm blood flow, superior mesenteric artery blood flow
      and right renal artery blood flow. Blood samples were assayed for noradrenaline,
      renin and atrial natriuretic peptide levels. Insulin sensitivity was assessed
      using the low dose short insulin tolerance test. RESULTS: There was a significant
      inverse correlation between forearm blood flow and insulin sensitivity (r = 
      0.67, P = 0.03), patients with lesser degrees of insulin sensitivity having the
      greater forearm blood flows. There was no correlation with the other haemodynamic
      or neurohumoral parameters. Patients with greater insulin resistance tended to
      have higher circulating endogenous insulin levels, although this relationship did
      not reach statistical significance (r = -0.53, P = 0.12). CONCLUSIONS: Insulin
      sensitivity appears to be an important determinant of skeletal muscle blood flow
      in heart failure. We speculate that this is secondary to the increased
      circulating endogenous insulin levels, and suggest that the therapeutic potential
      of exogenous insulin merits further investigation.

PMID- 9568453
TI  - Clinical outcome with enalapril in symptomatic chronic heart failure; a dose
      comparison. The NETWORK Investigators.
AB  - BACKGROUND: Angiotensin converting-enzyme (ACE) inhibitors used for the treatment
      of heart failure relieve symptoms, increase exercise performance, reduce hospital
      admissions and prolong life. The large survival studies have used higher doses of
      ACE inhibitors than those commonly used in clinical practice. NETWORK was set up
      to compare the effect of dose on the clinical outcome of ACE inhibition. METHODS
      AND PATIENTS: 1532 patients with heart failure drawn from primary care (n = 619)
      and hospital sources (n = 913) were randomized to receive enalapril 2.5 mg twice
      daily (n = 506). 5 mg twice daily (n = 510) or 10 mg twice daily (n = 516). The
      mean age was 70 years and 65% were male. Coronary heart disease was the cause of
      heart failure in 71%. Sixty-five percent were in NYHA class II and 35% in class
      III or IV. The mean left ventricular end-diastolic diameter was 59 (SD 11) mm.
      The incidence of the primary end-point of death, heart failure related
      hospitalization or worsening heart failure was assessed after follow-up of each
      patient for 24 weeks. FINDINGS: The number of patients reaching the primary end
      point was 62 (12.3%) in the 2.5 mg twice daily group, 66 (12.9%) in the 5 mg
      twice daily group and 76 (14.7%) in the 10 mg twice daily group. Deaths in each
      group were 21 (4.2%), 17 (3.3%) and 15 (2.9%), respectively. There were no
      significant differences in the results between the three groups. The crude
      relative risk for the combined end-point in the 10 mg twice daily group compared
      to the 2.5 mg twice daily group was 1.20 (95% CI 0.88 to 1.64). INTERPRETATION:
      NETWORK did not demonstrate a relationship between dose of enalapril and clinical
      outcome in patients with heart failure selected from both primary care and
      hospital practice.

PMID- 9568454
TI  - Familial hypertrophic cardiomyopathy. Cardiac ultrasonic abnormalities in
      genetically affected subjects without echocardiographic evidence of left
      ventricular hypertrophy.
AB  - AIMS: It is not known whether the apparent normality of echocardiographic
      examination results, in subjects bearing a mutation for hypertrophic
      cardiomyopathy but without ultrasonic left ventricular hypertrophy, is due to
      incomplete phenotypic expression, or inaccurate echocardiographic criteria. The
      aim of this study was to search for echocardiographic abnormalities in these
      patients. METHODS AND RESULTS: Echocardiography was performed in 100 subjects
      from two families with a mutation in the beta-MHC (720) or My-BPC (714) genes. We
      compared genetically affected subjects with an apparently normal left ventricle
      (thickness < 13 mm) (20 patients), and nonaffected first-degree relatives (61
      normal subjects). (1) Patients had a thicker left ventricular wall (9.7 +/- 1.4
      vs 8.9 +/- 1.4 mm, P = 0.03), a greater indexed mass (107 +/- 18 vs 97 +/- 17 g.
      m-2, P = 0.03), a larger left atrium (27 +/- 9 vs 23 +/- 10 mm3, P = 0.09) and
      lower wall stress (78 +/- 11 vs 89 +/- 15 10(3) dynes. cm-2, P = 0.002); these
      differences were highly significant after adjustment for height, age and systolic
      blood pressure either for wall thickness (P = 0.000003), mass (P = 0.005) or
      atrial volume (P = 0.001), and the ventricular systolic dimension appeared
      smaller (P = 0.01); (2) results remained significant (P < 0.01) when a lower cut
      off value (< or = 11 mm) or only adults (> or = 18 years) were considered; (3) a
      subanalysis of Family 714 (13 patients, 25 normals matched for sex, age and
      height) showed the same trends. CONCLUSION: In familial hypertrophic
      cardiomyopathy, genetically affected subjects with an apparently normal heart by
      echocardiography show slight ultrasonic structural and functional left
      ventricular modifications, suggesting that the phenotype of the disease is a
      continuous spectrum from normal structure to typical hypertrophy.

PMID- 9568456
TI  - Rate adaptation of QT intervals during and after exercise in children with
      congenital long QT syndrome.
AB  - OBJECTIVES: To improve the diagnostic criteria of the congenital long QT syndrome
      in borderline cases we examined rate adaptation of ventricular repolarization
      phases during exercise and subsequent recovery in children with the long QT
      syndrome and controls. METHODS: Nineteen children with definite long QT syndrome
      and 19 healthy controls underwent exercise testing. QT intervals were measured to
      the apex (early QT), to the end (total QT) and from apex to the end of the T wave
      (late QT) at heart rates from 90 by steps of 10 to 150 beats, min-1. RESULTS: In
      11/19 long QT syndrome patients (61%) and 2/19 controls (12%) the total QT
      lengthened during the recovery phase compared with exercise (P = 0.005) at the
      lowest comparable heart rate. No difference was found between the groups during
      exercise. The sensitivity of rate adaptation of repolarization intervals was
      analysed by calculating linear regression slopes relating the QT intervals to the
      heart rates. During recovery, slopes relating the total QT to heart rate were
      steeper in long QT syndrome patients than those in controls (-2.50 +/- 0.82 vs 
      1.79 +/- 0.47, P = 0.003). Total QT/heart rate slopes differed between exercise
      and recovery phases in the long QT syndrome group only (-1.77 +/- 0.71 vs 2.50 +/
      0.82, P = 0.009). In long QT syndrome patients, the difference in total QT/heart
      rate slopes was mainly because the late QT/heart rate slopes indicating
      inhomogeneity of repolarization were steeper during recovery (-1.27 +/- 0.74)
      than during exercise (-0.46 +/- 0.29, P < 0.0001). CONCLUSIONS: After exercise in
      long QT syndrome children the QT interval lengthens abnormally and inhomogeneity
      of repolarization increases. Evaluation of the QT interval, and especially its
      late portion after exercise, may help in establishing the diagnosis of long QT
      syndrome.

PMID- 9568455
TI  - Dipyridamole stress thallium-201 perfusion abnormalities in patients with
      hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome.
AB  - AIMS: Thallium-201 perfusion abnormalities are common in patients with
      hypertrophic cardiomyopathy and may be associated with an adverse prognosis in
      the young. The aim of this study was to prospectively determine the relationship
      between thallium-201 defects during dipyridamole stress to clinical presentation
      and outcome in a large consecutive series of patients with hypertrophic
      cardiomyopathy. METHODS/RESULTS: Thallium-201 single photon computed tomography
      was performed in 216 patients with hypertrophic cardiomyopathy during
      dipyridamole stress (0.5 mg. kg-1). Fixed perfusion defects occurred in 25%, and
      reversible defects in 22%. A combination of defects was present in 7%. Fixed
      defects were associated with: a history of syncope (17 of 46 with, vs 36 of 170
      without syncope, P = 0.03); larger left ventricular end-diastolic (46.9 +/- 7.4
      mm vs 43.3 +/- 6.4 mm; P = 0.001) and end-systolic dimension (30.2 +/- 8.4 mm vs
      24.5 +/- 5.9 mm, P < 0.0001); increased left atrial diameter (46.1 +/- 8.1 mm vs
      40.5 +/- 7.7 mm, P < 0.0001); lower fractional shortening (35.9 +/- 10.4% vs 43.8
      +/- 8.6%, P < 0.0001): and lower maximal exercise oxygen consumption (24.2 +/-
      8.1 ml. min-1. kg-1 vs 29.4 +/- 8.8 ml. min-1. kg-1, P < 0.0003). Reversible
      defects did not correlate with symptomatic status, but were associated with:
      larger left atrial dimensions (44.5 +/- 8.1 mm vs 41.0 +/- 8.0 mm; P = 0.009) and
      greater maximal left ventricular wall thickness (24.0 +/- 7.0 mm vs 20.6 +/- 7.0
      mm, P = 0.003). The mean follow up time was 41 +/- 21 months, range 0.6-124.
      There was no association between any thallium-201 abnormality and disease related
      death in young or adult patients. CONCLUSION: The present study shows that fixed
      thallium-201 perfusion defects detected during dipyridamole stress in patients
      with hypertrophic cardiomyopathy are associated with syncope, larger left
      ventricular cavity dimensions and reduced exercise capacity. Although the event
      rate was relatively small, there was no evidence for an association between
      thallium-201 defects and survival.

PMID- 9568457
TI  - Gastro-intestinal protein loss in late survivors of Fontan surgery and other
      congenital heart disease.
AB  - AIMS: Protein losing enteropathy is a serious complication of Fontan surgery. The
      aim of this study was to investigate gastro-intestinal protein loss in adults
      with congenital heart disease, both with and without Fontan surgery, and to
      correlate findings with systemic venous pressure. METHODS AND RESULTS: Forty
      eight patients were studied. The first group included adult survivors of Fontan
      surgery. The second and third groups were control patients with congenital heart
      disease who had not had Fontan surgery and had either normal or chronically
      elevated systemic venous pressure. Gastro-intestinal protein loss was assessed by
      measurement of faecal alpha-1-antitrypsin. Faecal alpha-1-antitrypsin levels were
      significantly higher in the Fontan group (0.55 +/- 0.15 mg. g-1 faeces, P =
      0.002) and the control group with chronically elevated venous pressure (0.60 +/-
      0.30 mg. g-1 faeces, P < 0.001) compared to the controls with normal venous
      pressure (0.29 = 0.12 mg. g-1 faeces). Of the 15 subjects who were found to have
      increased gastro-intestinal protein loss, only four had clinical protein-losing
      enteropathy. The degree of gastro-intestinal protein loss correlated
      significantly with venous pressure (P = 0.01) and with serum aspartate
      transaminase (P = 0.04). CONCLUSION: Increased gastro-intestinal protein loss is
      common in this select group of late survivors of Fontan surgery and in other
      subjects with congenital heart disease and chronic elevation of systemic venous
      pressure, and was present in patients who did not have protein-losing
      enteropathy. Increased faecal alpha-1-antitrypsin is an important finding in
      these patients as intervention at this stage, before the onset of florid protein
      losing enteropathy, might prevent the development of further complications.

PMID- 9568458
TI  - Spectrum of congenital heart disease in Malta. An excess of lesions causing right
      ventricular outflow tract obstruction in a population-base study.
AB  - AIMS: To quantify birth prevalence and spectrum of congenital heart disease in
      the Island population of Malta, and compare these rates with previous studies.
      METHODS: All patients diagnosed as having congenital heart disease by
      echocardiography, cardiac catheterization, surgery or post-mortem by 1 year of
      age between 1990-1994 were included. There were 231 cases of live born congenital
      heart disease with a birth prevalence of 8.8/1000 live births. The commonest
      lesions were ventricular septal defect, pulmonary stenosis and tetralogy of
      Fallot. The rates of individual lesions were compared with two recent
      epidemiological studies with similar methodologies. RESULTS: Although the overall
      birth prevalence of congenital heart disease was similar in three studies,
      significantly higher rates of pulmonary stenosis, tetralogy of Fallot and double
      outlet right ventricle were found in Malta, all of which predispose to right
      ventricular outflow tract obstruction. In contrast, there were lower rates of
      lesions causing left ventricular outflow tract obstruction. A higher rate of
      ventricular septal defect was also found. The Maltese gene pool may contain an
      inherent predisposition towards lesions causing right ventricular outflow tract
      obstruction.

PMID- 9568459
TI  - Univentricular heart.

PMID- 9568460
TI  - Where to publish European medical science?

PMID- 9568462
TI  - Effects of growth hormone and insulin-like growth factors on human osteoblasts.

PMID- 9568461
TI  - The effects of IGF-I and IGF-II on proliferation and differentiation of human
      osteoblasts and interactions with growth hormone.
AB  - BACKGROUND: We have previously shown that growth hormone (GH) consistently
      stimulates proliferation of human osteoblasts in vitro. In rat osteoblasts, GH
      augments the effects of insulin-like growth factor (IGF) I on cell proliferation
      and differentiation. We therefore investigated the effects of IGF-I and -II alone
      and in combination with GH on human osteoblasts in vitro. METHODS: Human
      osteoblast-like cells (HOB) were established from trabecular explants (n = 18)
      and human marrow stromal cells (HMS) from marrow aspiration (n = 21). The cell
      cultures were stimulated with IGF-I or IGF-II (1, 10 or 100 ng mL-1) alone, in
      combination with hGH (100 ng mL-1) or after prestimulation with hGH. RESULTS: IGF
      I alone, in combination with hGH and after pretreatment with hGH, increased
      proliferation of HOB and HMS by 49-190% (P < 0.05-0.01). IGF-II alone, in
      combination with hGH and after pretreatment with hGH increased proliferation of
      HOB by 57-158% (P < 0.01). In HMS only IGF-II in combination with hGH and after
      prestimulation with hGH increased proliferation. IGF-I alone and in combination
      with hGH decreased alkaline phosphatase (AP) in both cell types. IGF-II did not
      affect AP in HOB, but increased AP in HMS, this effect was abolished by hGH. In
      HOB, collagen production (PICP) was increased by IGF-II but unaffected by IGF-I.
      In HMS, PICP was decreased by IGF-I and -II but increased by hGH. Co-stimulation
      further increased PICP. CONCLUSION: IGF-I and -II exerted proliferative effects
      on both HOB and HMS. Co-stimulation with GH exhibited synergism in enhancing the
      proliferative response. In HMS prestimulation improved the proliferative response
      significantly. The effects of the IGFs on differentiation are more complex and
      dependent on cell maturation and of the IGF used.

PMID- 9568463
TI  - Glutathione homeostasis is disturbed in CD4-positive lymphocytes of HIV
      seropositive individuals.
AB  - BACKGROUND: Numerous in vitro tests have suggested that a disturbed cellular
      glutathione homeostasis plays an important role in the pathogenesis of human
      immunodeficiency virus (HIV) infection. METHODS: Using validated high-performance
      liquid chromatography (HPLC) methods, glutathione concentrations were determined
      in plasma and in cytosol of CD4+ lymphocytes and CD14+ cells of HIV-seropositive
      individuals and healthy control subjects. We measured concentrations of total
      glutathione, which is the sum of reduced (GSH) and oxidised (GSSG) glutathione
      and mixed disulphides of which there are two fractions: soluble mixed disulphides
      (GSSR) and protein bound glutathione (ProSSG). Also, non-protein-bound
      glutathione was measured, which is the sum of GSH, GSSG and GSSR. Thirty-five
      healthy control subjects and 35 HIV-infected individuals participated in the
      study. RESULTS: We found that in CD4+ lymphocytes from HIV-seropositive
      individuals, total glutathione levels were significantly higher than in healthy
      control subjects, whereas the fraction of non-protein-bound glutathione was not
      different. This can only be explained by an increase in the protein-bound
      fraction of glutathione indicating the presence of oxidative stress in CD4+
      lymphocytes of HIV-seropositive individuals. Glutathione measurements of cytosol
      of CD14+ cells and plasma were, however, not compatible with significant
      increased oxidation. Glutathione precursors (cysteine, cysteinylglycine,
      glutamylcysteine and homocysteine) and products of lipid peroxidation
      (thiobarbituric acid-reactive substances) were also measured in plasma and did
      not differ between healthy control subjects and HIV-seropositive individuals.
      CONCLUSION: We conclude that the glutathione homeostasis is disturbed in CD4+
      lymphocytes of HIV-seropositive individuals. The glutathione redox dysbalance in
      CD4+ lymphocytes could be important in the pathogenesis of HIV infection and have
      implications for therapy.

PMID- 9568464
TI  - Glutathione and HIV infection: reduced reduced, or increased oxidized?
AB  - Glutathione is the main intracellular defence against oxidative stress and
      regulates the cellular redox potential. HIV infection is accompanied by severe
      metabolic and immune dysfunctions. Several laboratories have demonstrated that
      the intracellular redox balance is disturbed in CD4+ T cells from HIV
      seropositive subjects, which may potentiate HIV replication and partly explain
      the immunological abnormalities associated with HIV disease. The importance of
      glutathione for immune function, regulation of gene expression, as well as
      therapeutic interventions with redox-active drugs are discussed in this
      commentary.

PMID- 9568465
TI  - Gastric emptying of the liquid, solid and oil phase of a meal in normal
      volunteers and patients with Billroth II gastrojejunostomy.
AB  - BACKGROUND: The relationship between gastric emptying of different phases of a
      meal in humans has only been partly studied in normal subjects and in patients
      with previous gastric surgery. METHODS: In the present study, gastric emptying of
      the liquid, solid and oil phase and the relationship between the phases was
      evaluated in 10 normal control subjects and in seven patients with Billroth II
      gastrojejunostomy using breath test technology. RESULTS: Gastric emptying in
      normal subjects showed a clear separation between the emptying of the liquid,
      solid and oil phase. In healthy volunteers, the liquid phase emptied in the same
      manner in the presence of a solid phase as in the presence of an oil phase. In
      contrast, the oil phase emptied more slowly with liquids than with solids. The
      emptying rate of the oil phase was not only inversely related to the amount
      administered but was also dependent on its chemical composition. Gastric emptying
      in patients with Billroth II gastroenterostomy was characterized by a complete
      loss of discrimination between the different phases of the meal, with an
      extremely fast emptying of the oil phase compared with normal control subjects.
      CONCLUSION: In normal subjects, the liquid, solid and oil phase of a meal are
      emptied differently. In patients with Billroth II gastrojejunostomy, dumping of
      the oil phase is the most pronounced difference from the normal physiology of
      gastric emptying. This could be one of the reasons why Billroth II gastrectomy
      may be associated with fat malabsorption.

PMID- 9568466
TI  - Different efficacy of soluble CD14 treatment in high- and low-dose LPS models.
AB  - BACKGROUND: About 50% of septic shock cases are attributed to Gram-negative
      bacteria or their cell wall compound lipopolysaccharide (LPS, endotoxin). An
      attractive therapeutic strategy could target the binding of LPS to its cellular
      receptors. In vitro the soluble form of the endotoxin receptor CD14 (sCD14)
      competitively prevents binding of LPS to membrane-bound CD14 and inhibits LPS
      stimulated macrophage responses. METHODS: We tested the in vivo endotoxin
      neutralizing capacity of human recombinant sCD14 using a mouse model of shock
      induced by 8 micrograms g-1 of LPS from Salmonella abortus equi. RESULTS: In this
      model, treatment with sCD14 reduced mortality if administered before or
      simultaneously with LPS. However, application of sCD14 had no effect on the
      secretion of early proinflammatory cytokines and did not protect the animals
      against the development of apparent shock symptoms and liver injury. sCD14 also
      failed to prevent LPS-inducible (7.5 ng g-1) liver injury in galactosamine
      sensitized mice. CONCLUSION: In line with these findings, sCD14 did not block LPS
      induced activation of Kupffer cells in vitro, which might explain why the
      compound only partially protected in vivo.

PMID- 9568467
TI  - Inflammatory bowel disease: no association between allele combinations of the
      interleukin (IL) I beta and IL-I receptor antagonist gene polymorphisms.
AB  - BACKGROUND: Interleukin 1 (IL-1) and its physiological antagonist interleukin-1
      receptor antagonist (IL-1 ra) play a crucial role in the pathogenesis of
      inflammatory bowel disease. Polymorphisms in the genes coding for these
      cytokines, the restriction enzyme TaqI polymorphism for IL-1 beta and the
      variable number of tandem repeats (VNTR) polymorphism for IL-1 ra, have been
      shown to influence cytokine synthesis in vitro. Recently, an association has been
      described for distinct allele combinations of these two polymorphisms in patients
      with ulcerative colitis and with Crohn's disease but not in healthy control
      subjects. METHODS: We studied 56 patients with ulcerative colitis, 64 patients
      with Crohn's disease and 196 healthy control subjects. All were unrelated
      Caucasians of European ancestry. After polymerase chain reaction (PCR) the
      amplification products were analysed on agarose gels. For the IL-1 beta
      polymorphism the PCR product was additionally digested using the restriction
      enzyme TaqI. RESULTS: The allele and genotype frequencies as well as the carriage
      rates of the IL-1 beta TaqI polymorphism in healthy control subjects were in
      agreement with previous findings in other populations. Allele and genotype
      frequencies of the IL-1 beta polymorphism were not different in inflammatory
      bowel disease patients compared with healthy control subjects. Comparing allele
      combinations of both polymorphisms no association could be identified either
      within healthy control subjects or in the groups of patients with ulcerative
      colitis or Crohn's disease. CONCLUSION: Thus, we could not confirm the results of
      a previous study reporting an association between the IL-1ra and IL-1 beta gene
      polymorphisms in patients with inflammatory bowel disease.

PMID- 9568468
TI  - Direct gene transfer into the rat pancreas using DNA-liposomes.
AB  - BACKGROUND: Pancreatic cancer represents a malignancy with very poor clinical
      prognosis and limited therapeutic potential. Recent developments of gene transfer
      technology offer new therapeutic avenues by delivering recombinant genes directly
      into normal or neoplastic tissue in vivo. METHODS: Here we show that the LacZ
      marker gene, complexed to cationic liposomes, can be introduced into the pancreas
      by either intraductal or intra-arterial injection. Expression of the beta
      galactosidase gene product was monitored by polymerase chain reaction and
      histochemistry. RESULTS: Up to 28 days after in vivo gene transfer, beta
      galactosidase activity could be demonstrated in the pancreas. Intraductal
      application induced gene expression in lining duct cells preferentially. Twenty
      four hours after intraductal injection of liposomes, a dose-dependent, transient
      increase in serum amylase levels was detected. Nevertheless, no histological
      signs of pancreatitis were evident. Intra-arterial injection resulted in beta
      galactosidase expression in endothelial cells of intrapancreatic arteries, as
      well as in the spleen, lymph nodes and liver, but not in ductal cells of the
      pancreas. Only occasionally were acinar cells positive for blue staining by
      either type of treatment. CONCLUSION: These experiments demonstrate that in vivo
      gene transfer into the pancreas is feasible using DNA-liposome complexes.
      Furthermore, the route of administration largely determines cell type specificity
      and side-effects. This technique might have an impact for the development of gene
      therapy strategies for pancreatic diseases.

PMID- 9568469
TI  - Effects of anti-C5a monoclonal antibodies on oxygen use in a porcine model of
      severe sepsis.
AB  - METHODS: We analysed the effects of complement depletion and of C5a inhibition on
      haemodynamic parameters, oxygen delivery (DO2), oxygen consumption (VO2), oxygen
      extraction ratio (OER) and blood lactate levels after live bacteria infusion in
      pigs. RESULTS: In the first series of experiments, animals were decomplemented by
      cobra venom factor (CVF, 125 micrograms kg-1) and challenged with 1.3 x 10(9)
      Escherichia coli kg-1. In a second series, animals were treated with neutralizing
      anti-C5a monoclonal antibodies (mAb) T13/9 before infusion of an increased E.
      coli dosage (1 x 10(10) E. coli kg-1). Administration of Gram-negative bacteria
      resulted in hypotension, tachycardia, pulmonary hypertension and decreased
      cardiac output typical for severe sepsis. These alterations were more pronounced
      in animals challenged with a higher bacteria concentration (1 x 10(10) E. coli kg
      1, n = 5) than with a lower dosage (1.3 x 10(9) E. coli kg-1, n = 4). Complement
      depletion by CVF injection 24 h before E. coli infusion (n = 4), or anti-C5a mAb
      T13/9 administration (n = 4) had no effect on the changes in haemodynamic
      parameters and in DO2 associated with E. coli challenge. Application of either
      1.3 x 10(9) or 1 x 10(10) E. coli kg-1 resulted in a marked decrease in VO2 and
      an increase in blood lactate levels, whereas the OER did not change throughout
      the experiment. In contrast, pretreatment with CVF 24 h before low-dose E. coli
      (1.3 x 10(9) kg-1) administration resulted in a significant increase in VO2 (P <
      0.05) and in OER (P < 0.05) compared with untreated septic animals (n = 4). No
      hyperlactaemia occurred in complement-depleted septic animals compared with
      complement-sufficient animals (P < 0.05). Animals challenged with a high E. coli
      dose (1 x 10(1) kg-1) and treated with anti-C5a mAbs showed a pronounced increase
      in VO2 and OER (P < 0.05) accompanied by an attenuated increase in lactate levels
      (P < 0.05) compared with untreated septic animals. CONCLUSION: The results
      demonstrate an improved oxygen use after complement depletion in this model of
      severe Gram-negative sepsis. Furthermore, a similar effect was seen after
      specifically neutralizing C5a by mAbs, indicating a role of C5a in the underlying
      mechanism.

PMID- 9568470
TI  - Gemfibrozil-induced decrease in serum ubiquinone and alpha- and gamma-tocopherol
      levels in men with combined hyperlipidaemia.
AB  - BACKGROUND: Low blood levels of antioxidants are associated with an increased
      risk of developing coronary artery disease. Lipophilic antioxidants are
      transported in lipoproteins, and hypolipidaemic therapy may therefore alter their
      blood concentrations. METHODS: The present randomized, placebo-controlled cross
      over study of 21 men with combined hyperlipidaemia examines whether 10-12 weeks
      of gemfibrozil treatment affects the serum concentrations of the antioxidants
      ubiquinone-10 or alpha- or gamma-tocopherol. RESULTS: Gemfibrozil treatment
      lowered plasma triglycerides and both total and very low-density lipoprotein
      (VLDL)-cholesterol (P < 0.001 for all by ANOVA), whereas high-density lipoprotein
      (HDL)-cholesterol increased (P < 0.001). The median serum levels of ubiquinone-10
      decreased from 1.30 mumol L-1 (interquartile range 0.87-1.71 mumol L-1) with
      placebo to 0.76 mumol L-1 (0.66-0.95) with gemfibrozil treatment (P < 0.001).
      Corresponding levels for alpha- and gamma-tocopherol were: 68.5 mumol L-1 (51.1
      84.7) vs. 40.8 mumol L-1 (30.3-55.0) and 8.6 mumol L-1 (5.2-16.7) vs. 4.3 mumol L
      1 (3.5-7.0) respectively (P < 0.001 for both). The decrease in serum antioxidants
      was also evident when standardized for total cholesterol (P < 0.05) or LDL
      cholesterol (P < 0.001). Normolipaemic control subjects had significantly lower
      antioxidant levels than placebo-treated patients: ubiquinone 0.63 mumol L-1 (0.41
      1.05), alpha-tocopherol 34.3 mumol L-1 (27.3-45.6) and gamma-tocopherol 3.2 mumol
      L-1 (2.5-4.2) (P < 0.001 for all). The association of antioxidants with
      lipoprotein lipids was further established by positive correlations between the
      levels of antioxidants and those of total cholesterol (r = 0.64, P < 0.001) or
      total triglycerides (r = 0.71, P < 0.001). CONCLUSION: Gemfibrozil treatment of
      men with combined hyperlipidaemia reduces serum antioxidant levels to the levels
      seen in healthy normolipidaemic men. The mechanisms and the relevance of this
      finding remain unclear and need to be addressed in further studies.

PMID- 9568471
TI  - Forearm composition contributes to differences in reactive hyperaemia between
      healthy men and women.
AB  - BACKGROUND: Post-ischaemic reactive hyperaemia in the forearm has been suggested
      as a marker of resistance vessel function. The contribution of forearm
      composition to the kinetics of reactive hyperaemia is largely unknown. The body
      composition of men and women differs in that women have a higher body fat content
      and less lean body mass. METHODS: In the present study, we investigated whether
      the kinetics of reactive hyperaemia in the forearm in 14 healthy subjects (seven
      men and seven women) show gender-specific differences and whether forearm
      composition contributes to such differences. RESULTS: Peak reactive hyperaemic
      flow as well as 1-min-flow debt repayment (measured by venous occlusion
      plethysmography) were significantly higher in male than in female study
      participants. This difference was explained to > 60% by gender-specific
      differences in forearm relative muscle mass (as determined by magnetic resonance
      imaging). The half-life of the reactive hyperaemic response, on the other hand,
      was not different between men and women and did not show an association with
      forearm muscle. CONCLUSION: Our results demonstrate that forearm composition must
      be considered if peak reactive hyperaemic or flow debt repayment is used as a
      target, and that dynamic measurements of the reactive hyperaemic process are more
      suitable to describe the function of resistance arteries than single-point
      observations.

PMID- 9568472
TI  - Effects of endotracheal intubation on airway neuropeptide content, arterial
      oxygenation and lung volumes in anaesthetized rats.
AB  - BACKGROUND: General anaesthesia affects lung volume and pulmonary gas exchange.
      What role is played by mechanical stimulation by the endotracheal tube? METHODS:
      We investigated the effects of intubation on arterial oxygenation and lung volume
      in rats. RESULTS: Endotracheal intubation caused an increase in PA-aO2 and volume
      of trapped gas in the lung. This was accompanied by a reduction in neuropeptides
      and calcitonin gene-related peptide (CGRP) in trachea, bronchi and lung, and in
      vasoactive intestinal peptide (VIP) in the trachea. The increase in PA-aO2 and
      volume of trapped gas due to intubation was not altered in the animals given
      capsaicin, in which neuropeptide levels were reduced. CONCLUSIONS: These data
      suggest that the decrease in CGRP and VIP content in the airway tissues may be
      one of the consequences, but not the cause, of impaired gas exchange by
      endotracheal intubation. The increase in volume of trapped gas in the lung is
      apparently not mediated by activation of capsaicin-sensitive sensory nerves.

PMID- 9568473
TI  - The effects of sodium substitution on currents determining the resting potential
      in guinea-pig ventricular cells.
AB  - It has recently been shown that a sodium background current, ib,Na, exists in
      cardiac muscle cells whose effect is to depolarize the membrane so that the
      resting potential, Vm, is positive to the potassium equilibrium potential, EK. In
      ventricular cells, where ib,Na is smallest, Vm is about 10 mV positive to EK (EK
      = -87 mV at 37 degrees C). Yet, replacement of Na+ ions by large impermeant
      cations does not cause the expected hyperpolarization. We have studied this
      problem in guinea-pig myocytes using a single microelectrode recording technique
      in combination with a rapid external solution switch. Cells depolarized < or =
      0.5 mV from potentials between -80 and -73 mV and hyperpolarized up to 5 mV from
      potentials between -73 and -64 mV when 70 mM choline chloride or N-methyl-D
      glucamine chloride were used to replace 70 mM Na+ in the bathing solution.
      Replacement by 70 mM lithium chloride, however, only caused hyperpolarization in
      very depolarized cells when the voltage change was much smaller. The changes were
      complete almost as soon as the solution change, i.e. within 250 ms, indicating
      that the actions are attributable to the external solution change rather than to
      secondary changes in intracellular concentrations. Patch clamp recording was used
      to investigate the mechanism involved. These experiments showed that the presence
      or absence of the inward rectifier current iK1 determines in which direction Na+
      removal acts. In the absence of iK1 the changes are attributable to removal of
      ib,Na, whereas in the presence of iK1 the changes resemble the i(V) relation for
      iK1, implying that Na+ regulates iK1 in a way that can mask the changes in ib,Na.
      These results explain why removal of Na+ does not lead to hyperpolarization in
      ventricular cells as would be expected if changes in ib,Na were solely
      responsible. Computer reconstruction shows that the effects may be attributed to
      actions of sodium removal on the conductance and gating of iK1.

PMID- 9568474
TI  - Calcium-activated transient membrane currents are carried mainly by chloride ions
      in isolated atrial, ventricular and Purkinje cells of rabbit heart.
AB  - Under physiological conditions, calcium-dependent ([Ca2+]i-dependent) Cl-
      currents (ICl(Ca)) have been suggested to participate in the repolarizing
      processes. In this paper, the possible contribution of ICl(Ca) to transient
      inward currents and, hence to arrhythmias, has been studied in myocytes from the
      working myocardium and from the conductive system. Single atrial, ventricular and
      Purkinje cells, isolated enzymatically from rabbit heart, have been studied under
      whole-cell voltage-clamp and were internally perfused with the fluorescent Ca2+
      indicator, fura-2 (100 microM). Ca2+ release from the sarcoplasmic reticulum was
      either induced by external application of caffeine or occurred spontaneously in
      Ca(2+)-overloaded cells. Membrane currents accompanying Ca2+ transients showed
      linear current-voltage characteristics between -60 and +80 mV as evidenced from
      fast voltage ramps. When intra- and extracellular Cl- concentrations were kept
      symmetrical in the absence of the Na(+)-Ca2+ exchange mechanism, transient
      currents had a reversal potential close to 0 mV. Reduction of external Cl-
      concentration shifted this reversal potential towards the new Cl- equilibrium
      potential. Neither the time course of the transient currents nor the shift in
      their reversal potentials was significantly affected by the presence of Na+.
      Approximately 90% of this current was blocked by the application of the Cl-
      channel blocker, anthracene-9-carboxylic acid (0.5 mM) at +80 mV. It is
      concluded, that [Ca2+]i-activated transient membrane currents in atrial,
      ventricular and Purkinje cells of rabbit heart are mainly due to the activation
      of a [Ca2+]i-dependent Cl- current.

PMID- 9568475
TI  - Effects of short chain fatty acids and carbon dioxide on magnesium transport
      across sheep rumen epithelium.
AB  - Short chain fatty acids (SCFAs) and CO2 have been shown to stimulate net Mg2+
      efflux from the isolated reticulorumen in vivo. To investigate the underlying
      mechanisms of Mg2+ transport we performed Ussing chamber and microelectrode
      experiments and measured 28Mg2+ fluxes across sheep rumen epithelium in vitro. In
      the presence of SCFAs mucosal-to-serosal Mg2+ flux (Jm-sMg) amounted to 82.3 +/-
      7.8 nmol cm-2 h-1 and serosal-to-mucosal Mg2+ flux (Js-mMg) to 3.2 +/- 0.7 nmol
      cm-2 h-1. Replacing SCFAs with gluconate caused a 50% reduction of Jm-sMg,
      whereas Js-mMg was not affected. Among the SCFAs, n-butyrate was more effective
      in stimulating Jm-sMg than acetate, propionate or iso-butyrate. Eliminating HCO3(
      )-CO2 from SCFA-containing solutions did not affect Mg2+ fluxes, whereas the same
      replacement in SCFA-free solutions led to a further reduction in Jm-sMg. Jm-sMg
      decreased after the addition of ethoxyzolamide to SCFA-free, bicarbonate buffered
      solutions. Decreasing mucosal pH from 6.4 to 5.4 increased Jm-sMg in SCFA-free,
      bicarbonate buffered solutions. SCFAs had no effect on the apical membrane
      potential of rumen epithelial cells. The experiments show that both SCFAs and CO2
      stimulate Mg2+ transport through an increase in Jm-sMg, most probably via
      stimulation of a Mg(2+)-2H+ exchange mechanism. SCFAs may have additional
      metabolic effects on Mg2+ transport.

PMID- 9568476
TI  - Bone mineral density and composition in rat pregnancy: effects of streptozotocin
      induced diabetes mellitus and insulin replacement.
AB  - A disturbed calcium homeostasis characterizes diabetic pregnancy. This study
      documents changes in bone mineral composition in diabetic pregnant rats and
      examines the effect of insulin replacement. Control pregnant (CP), diabetic
      pregnant (DP) and insulin-treated DP (DPi) rats were assessed for femoral calcium
      and magnesium content, bone mineral density (BMD) and the ratio of hypertrophic
      to maturing and proliferative cells in the femoral growth plate. DP rats showed a
      significantly (P < 0.01) lower body weight, femoral weight and length than CP
      rats. Femoral calcium and magnesium content was also significantly (P < 0.05)
      lower in DP rats, as was ash weight. When calcium and magnesium were normalized
      for ash weight no significant differences were apparent. A significantly (P <
      0.05) lower total BMD at the distal femur was seen in DP rats. This comprised a
      significantly (P < 0.01) lower trabecular BMD with no significant change in
      cortical BMD. A significantly (P < 0.05) higher ratio of hypertrophic to maturing
      and proliferative cells of the femoral growth plate was evident in DP animals.
      DPi rats showed normal blood glucose concentrations and femoral growth plate
      histology. DPi rats also showed normal femoral weight and length but only
      partially restored femoral ash weight and mineral content. Insulin failed to
      normalize total or trabecular BMD. Diabetes mellitus clearly has a marked effect
      on bone growth and mineral content in pregnancy which may be relevant to overall
      calcium homeostasis. The lower bone growth, bone calcium content and trabecular
      BMD may be unfortunate consequences of the marked hypercalciuria reported
      elsewhere in diabetes and may serve to maintain normocalcaemia in the disease.

PMID- 9568477
TI  - The effects of skin brushing on H reflex amplitude in normal human subjects.
AB  - Experiments were performed on twenty-two neurologically normal subjects in order
      to investigate the effects of skin brushing on H reflex excitability in triceps
      surae. H reflex amplitude was observed to decrease during brushing of a 2 cm x 10
      cm area of skin overlying triceps surae, returning to control levels when
      brushing ceased. Alterations in the duration of the brushing period did not
      affect the magnitude of the H reflex inhibition, although increased frequency of
      brush strokes per minute slightly increased the amount of inhibition observed.
      Brushing of smaller skin areas overlying the muscle only sometimes resulted in H
      reflex inhibition. Brushing over other skin areas of the lower limb produced only
      slight effects on triceps surae H reflex amplitude. Removal of cutaneous input
      from the skin overlying triceps surae abolished any effects of brushing in this
      area on H reflex amplitude. These results demonstrate an inhibitory effect of
      brushing on H reflex excitability in normal subjects. If such results are
      confirmed in subjects with neurological deficit, they could have implications for
      the use of brushing in clinical practice.

PMID- 9568478
TI  - The glucose transporter of human erythrocytes--working hypothesis for its
      functional mechanism.

PMID- 9568479
TI  - Membrane-bound glyceraldehyde-3-phosphate dehydrogenase and multiphasic
      erythrocyte sugar transport.
AB  - Net sugar import by human erythrocytes consists of ATP-modulated rapid and slow
      phases while sugar export consists of a single slow phase. We have proposed that
      this behaviour results from obligate substrate tunnelling from transporter to
      bulk cytosol through a complex containing high-affinity, low-capacity sugar
      binding sites (Cloherty, Sultzman, Zottola & Carruthers, 1995). Glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) is known to compartmentalize ATP delivery to
      erythrocyte membrane ATPases and interact directly with the erythrocyte glucose
      transporter in vitro. The present study examines the possibility that GAPDH is an
      obligate component of the hypothesized sugar-binding complex. GAPDH remains
      associated with the erythrocyte membrane following cell lysis and remains
      associated with the cytoskeleton under conditions where more than 99% of the
      membrane glucose transport protein (GLUT1) is released by detergent (Triton X
      100). GAPDH is released from erythrocyte membranes upon exposure to Mg.ATP or to
      NADH. ATP displacement of membrane-bound GAPDH is half-maximal at 200 microM ATP
      and appears to involve ATP interaction with multiple, co-operative sites. GAPDH
      interaction with purified tetrameric GLUT1 is saturable, co-operative and also
      inhibited by ATP. ATP inhibition of GAPDH binding to purified tetrameric GLUT1 is
      less effective than ATP inhibition of GAPDH binding to intact erythrocyte
      membranes. Removal of cellular GAPDH by exposing erythrocyte membranes to NADH
      prior to membrane resealing neither affects ATP modulation of sugar transport nor
      reduces biphasic net sugar uptake to a single phase. We conclude that ATP
      sensitive GAPDH interaction with the cytoplasmic surface of erythrocyte membranes
      and GLUT1 is responsible neither for ATP modulation of sugar transport nor for
      multiphasic net sugar import by human red cells.

PMID- 9568480
TI  - Adenosine and hypoxanthine transport in horse erythrocytes: evidence for a
      polymorphism in the transport of hypoxanthine via a sodium-dependent
      cotransporter.
AB  - The inward transport of two purines, adenosine and hypoxanthine, at 37 degrees C
      by horse erythrocytes was compared. No mediated transport of adenosine was
      detected in horse erythrocytes, nor was saturable, high-affinity binding of the
      potent facilitated-diffusion inhibitor nitrobenzylthioinosine demonstrable in
      horse erythrocyte membranes. In contrast, erythrocytes from most horses possessed
      a saturable sodium-dependent hypoxanthine transporter (apparent K(m), 100 +/- 28
      microM; Vmax, 0.20 +/- 0.08 mmol (l cells)-1 h-1; means +/- S.E.M., n = 5).
      Guanine inhibited hypoxanthine influx (apparent Ki, 24 +/- 6 microM), but adenine
      and xanthine had no effect. Unlike human erythrocytes, no sodium-independent
      hypoxanthine transporter was detected in horse erythrocytes. There are, however,
      a small number of animals (approximately 15%) whose erythrocytes fail to
      transport hypoxanthine. This variation appears to be under genetic control, but
      the precise nature of the control is unknown.

PMID- 9568481
TI  - System y+L: the broad scope and cation modulated amino acid transporter.
AB  - The properties are discussed of system y+L, a broad scope amino acid transporter
      which was first identified in human erythrocytes. System y+L exhibits two
      distinctive properties: (a) it can bind and translocate cationic and neutral
      amino acids, and (b) its specificity varies depending on the ionic composition of
      the medium. In Na+ medium, the half-saturation constant for L-lysine influx was
      9.5 +/- 0.67 microM and the inhibition constant (Ki) for L-leucine was 10.7 +/-
      0.72 microM. L-Leucine is the neutral amino acid that binds more powerfully,
      whereas smaller analogues, such as L-alanine and L-serine interact less strongly
      (the corresponding inhibition constants were Ki,Ala, 0.62 +/- 0.11 mM; Ki,Ser,
      0.49 +/- 0.08 mM). In the presence of K+, the carrier functions as a cationic
      amino acid specific carrier, but Li+ is able to substitute for Na+ facilitating
      neutral amino acid binding. The effect of the inorganic cations is restricted to
      the recognition of neutral amino acids; translocation occurs at similar rates in
      the presence of Na+, K+ and Li+. The only structural feature that appears to
      impair translocation is bulkiness and substrates with half-saturation constants
      differing by more than 100-fold translocate at the same rate. This suggests that
      translocation is largely independent of the forces of interaction between the
      substrate and the carrier site. System y+L activity has been observed in Xenopus
      laevis oocytes injected with the cRNA for the heavy chain of the 4F2 human
      surface antigen. 4F2hc is an integral membrane protein with a single putative
      membrane-spanning domain and it remains to be clarified whether it is part of the
      transporter or an activator protein.

PMID- 9568482
TI  - Kinetics of the P-glycoprotein, the multidrug transporter.

PMID- 9568483
TI  - The relation between local cerebral blood flow and extracellular glucose
      concentration in rat striatum.
AB  - The effect of anaesthetics on the relation between local cerebral blood flow
      (rCBF) and extracellular glucose was studied in rat striatum. Cerebral blood flow
      was measured using the hydrogen clearance method and extracellular glucose using
      an implanted glucose oxidase-based biosensor. Rats were given an intraperitoneal
      (i.p.) injection of either sodium pentobarbitone (60 mg kg-1) or chloral hydrate
      (350 mg kg-1). The effect of the i.p. injection, as demonstrated by an i.p.
      saline injection, was a brief increase in rCBF accompanied by a decrease in
      glucose. Sodium pentobarbitone produced a decrease in both rCBF and glucose,
      whereas chloral hydrate caused a decrease in glucose but an increase in rCBF.
      These findings show a dissociation between rCBF and extracellular glucose and
      suggest that glucose in the extracellular compartment is not derived directly
      from the blood vascular compartment.

PMID- 9568484
TI  - Glucose transport inhibitors protect against 1,2-cyclohexanedione-produced
      potassium loss from human red blood cells.
AB  - It has been suggested that the glucose transport system of human erythrocytes
      contains an arginine shield to prevent the leak of potassium through the
      transporter. To investigate this suggestion we treated human erythrocytes with
      the specific arginine reagent 1,2-cyclohexanedione. Under conditions which
      produce a covalent reaction between arginine and the reagent, a steady leak of
      potassium occurs. If glucose, maltose or the inhibitor phloretin are present
      during the reaction the extent of the leak is reduced. These findings support the
      view that arginines have a role in preventing potassium loss through the glucose
      transporter.

PMID- 9568485
TI  - Channelling free energy into work in biological processes.
AB  - The process by which free energy from ATP or an ion gradient is coupled to work-
      either osmotic work, by a membrane pump, or mechanical work, by a molecular motor
      -as well as the development of force by a molecular motor, can be explained by
      mechanisms dependent on substrate binding energy. Coupling involves a reaction
      sequence that combines the driving and driven reactions and that is controlled at
      switch points where the mobility of the coupling protein and its specificity in
      binding and catalysis can be abruptly altered; the altered state is an
      intermediate (or transition state) in the coupled reaction, the unaltered state
      an intermediate in the uncoupled reaction (slippage). The balance between these
      states, which is determined by the increase in substrate binding energy in the
      transformation, decides the relative importance of the coupled and uncoupled
      paths. On this basis a general expression for switching may be derived: the
      tightness of coupling is limited by a ratio of substrate dissociation constants
      before and after a controlling change in state: Rate(coupled)/Rate(uncoupled) <
      or = Kinitial state/Kfinal state. When binding energy is used in this way to
      distort the conformation of a protein, mechanical work is done; the work is
      internal but becomes external if the protein is connected to an external load.
      External work, force F multiplied by distance d, is then limited by a ratio of
      substrate dissociation constants before and after the conformational change: W =
      Fd < RT In(Kinitial state/Kfinal state). The ratios of dissociation constants,
      estimated from published values of the force exerted by molecular motors, are > 1
      x 10(4) for myosin and > 2 x 10(4) for kinesin. From the tightness of coupling of
      the anion exchange carrier of red cells the ratio of constants for coupling is >
      or = 4 x 10(4). These increments can be accounted for by conversion of a surface
      complex to an enclosed complex, as in chelate formation. The work done by an ATP
      driven motor is limited by the free energy of ATP hydrolysis, but the force
      developed is independent of the ATP reaction, and comes from binding energy with
      either the driving or driven substrate.

PMID- 9568486
TI  - Evidence from temperature studies that the human erythrocyte hexose transporter
      has a transient memory of its dissociated ligands.
AB  - The inhibition constant of L-sorbose efflux (Ki(sorbose)) from human erythrocytes
      for inhibition by D-glucose increases from 5.15 +/- 0.89 to 12.24 +/- 1.9 mM on
      cooling from 50 degrees C to 30 degrees C; the Ki(sorbose) of D-mannose increases
      similarly on cooling. The activation energy Ea(sorbose) of net L-sorbose exit
      from human erythrocytes is 62.9 +/- 3.1 kJ mol-1; but in the co-presence of 5 mM
      D-glucose Ea(sorbose) is reduced to 41.7 +/- 1.6 kJ mol-1 (P < 0.005). These data
      are consistent with the view that when D-glucose binds to the hexose transporter
      it leads to an activated transporter state which remains transiently activated
      after glucose dissociates; if L-sorbose binds to the excited state it is more
      mobile than otherwise and consequently the apparent Ki(sorbose) of D-glucose is
      raised. Cooling prolongs the decay time of the activated state; hence the
      Ki(sorbose) of D-glucose rises as temperature is reduced.

PMID- 9568487
TI  - Mitochondrial carrier proteins can reversibly change their transport mode: the
      cases of the aspartate/glutamate and the phosphate carrier.
AB  - A number of mitochondrial carrier systems function both in homologous and in
      heterologous exchange mode, which, in the case of the phosphate carrier is a
      homologous Pi(-)-Pi- and a heterologous Pi(-)-OH- exchange. In addition, we
      showed that mitochondrial carriers, e.g. the aspartate/glutamate and the
      phosphate carrier, can undergo a functional shift from coupled antiport to
      uncoupled uniport after modification of cysteine residues. In this transport mode
      a mixture of carrier- and channel-type properties is observed. To address this
      question on the molecular level, the phosphate carrier from yeast (S. cerevisiae)
      mitochondria was expressed in E. coli, solubilized, purified and functionally
      reconstituted. From three cysteine residues present in the yeast phosphate
      carrier at positions 28, 134 and 300, only one single cysteine residue (C28) was
      found responsible for the functional switch from antiport to uniport. Upon
      replacement by a serine residue, this interconversion was blocked. After
      incorporation of the carrier into giant liposomes, electrophysiological methods
      (patch clamp) were applied. Under these conditions, a fourth transport mode of
      the phosphate carrier was observed, namely an action as anion-selective channel,
      which could be reversibly blocked by phosphate.

PMID- 9568488
TI  - Proteins that interact with facilitative glucose transporters: implication for
      function.
AB  - The cellular uptake of glucose catalysed by the facilitated glucose transporter
      (GLUT) family is further regulated by metabolites and hormones, most importantly
      by insulin. All of the six isoforms known in this family possess a large
      cytoplasmic domain of divergent amino acid sequence. A body of evidence indicates
      that this domain is important for GLUT regulation. Exactly how this domain
      participates in the regulation, however, is not known. A likely possibility is
      that a specific cellular protein interacts with GLUT at this domain, and thus
      modulates the function. This putative, glucose transporter binding protein (GTBP)
      may be an enzyme, or a non-enzymic adaptor or docking protein. Indeed, we have
      identified several cellular proteins that bind to the cytoplasmic domain of GLUT
      proteins; these include glyceraldehyde-3-phosphate dehydrogenase, glucokinase,
      GTBP70, GTBP85, GTBP28 and L-3-hydroxyacyl-CoA dehydrogenase. Some of these GLUT
      GTPB interactions are functionally coupled. Whether any of these interactions
      actually participates in the insulin-induced GLUT regulation is yet to be
      determined.

PMID- 9568489
TI  - Medicare GME funding undergoes changes.

PMID- 9568490
TI  - Literature searches: how important are they?

PMID- 9568491
TI  - More on Haiti.

PMID- 9568492
TI  - Financing predoctoral family medicine education.

PMID- 9568493
TI  - Is attending a teaching skills workshop worth your time?

PMID- 9568495
TI  - Recognition of Alzheimer's disease: the 7 Minute Screen.
AB  - BACKGROUND AND OBJECTIVES: Because Alzheimer's disease (AD) tends to be
      underdiagnosed, we developed a brief neurocognitive screening battery to identify
      AD patients. The 7 Minute Screen consists of four individual tests (orientation,
      memory, clock drawing, verbal fluency). The screen can be rapidly administered
      and scored and therefore may be appropriate for use in the primary care setting.
      This study determined the validity and reliability of the 7 Minute Screen in
      distinguishing patients with AD from healthy controls. METHODS: The 7 Minute
      Screen was administered to 60 consecutive referrals to a memory disorders clinic
      who were subsequently diagnosed with probable AD and to 60 community-dwelling
      individuals. Analysis of the combined scores on the four individual tests was
      used to determine the probability of dementia in each subject. We also evaluated
      test-retest and inter-rater reliability, as well as the time required to
      administer the battery. RESULTS: When compared with the normal subjects, the
      patients with AD were significantly more impaired on each of the four tests
      included in the 7 Minute Screen. When the four tests were combined into a
      logistic regression model, the battery correctly diagnosed 92% of the patients
      with AD and 96% of the normal subjects. The battery performed equally well when
      only patients with mild and very mild AD were included. Mean time for
      administration and scoring was 7 minutes 42 seconds. CONCLUSIONS: The 7 Minute
      Screen is a reliable and valid instrument for identifying patients with AD. It
      appears to be a potentially useful tool for identifying patients with AD in a
      primary care setting.

PMID- 9568494
TI  - A disposable adhesive patch for stress urinary incontinence.
AB  - BACKGROUND AND OBJECTIVES: Stress urinary incontinence (SUI) affects 5 million
      women in the United States. Current surgical and pharmacological management
      options are often unsuccessful, forcing many sufferers to rely on bulky and
      uncomfortable sanitary protection. This study evaluated the safety, efficacy, and
      acceptability of a small, disposable adhesive patch designed to seal the urethral
      opening and prevent urine leakage. METHODS: Thirty-seven women with mild-to
      moderate SUI were recruited from a suburban community. Each volunteer
      participated in a 21-week protocol that included a 1-week qualifying period, 4
      week (pretest) control period, 12-week patch-use period, and 4-week (posttest)
      control period. Patch efficacy was evaluated with quantitative (leakage into
      sanitary napkin) and qualitative (voiding diary) measures of urine leakage.
      Symptom questionnaires were also completed. RESULTS: Overall leakage was reduced
      by 60%, from 1.1 +/- .3 standard error of the mean (SEM) to .44 +/- .11 (SEM)
      grams of urine per hour. Perception of dryness, measured by voiding diaries,
      improved 67%, from 13.3 +/- 1.9 (SEM) to 4.3 +/- 0.9 (SEM) leakage episodes per
      week. Safety evaluation included peri-urethral cytology, urinalysis and urine
      culture, and vaginal cultures. All measures were unaffected by 3 months of patch
      use. Acceptability was assessed with questionnaires that measured the impact of
      patch use on activities of daily living and overall quality of life. Women
      reported a significant improvement in both measures. All but one volunteer found
      that the patch was comfortable and were able to place it correctly between the
      inner labia with written instructions only. CONCLUSIONS: The disposable patch
      significantly reduced urine leakage resulting from SUI in community-based women.
      Dryness improved significantly, both by measurement of actual leakage and by the
      subject's perception of dryness. The maturation index of the vestibular tissues
      showed an increase in the number of superficial cells during patch use.
      Otherwise, there were no significant changes in vulvar tissues, urine
      composition, or microbial flora (in vaginal and urine samples). Volunteers
      reported that the patch improved their overall quality of life.

PMID- 9568496
TI  - Emergency department use by family practice patients in an academic health
      center.
AB  - BACKGROUND AND OBJECTIVES: With the proliferation of managed care, efforts are
      being made to reduce emergency department (ED) use after hours and eliminate
      unnecessary ambulatory visits during office hours. This study characterized the
      after-hours ED use by a family practice residency patient population and
      determined differences in appropriate ED use by patients calling ahead versus
      those arriving at the ED without calling first. American College of Emergency
      Physicians guidelines were used to define appropriateness of visit. METHODS: A
      retrospective ED chart and on-call log review were used to obtain data. RESULTS:
      A random sampling of family practice patients from January 1993 to December 1994
      (n = 332) showed that, overall, 62% of patients did not call prior to their ED
      visit. Calling ahead was not associated with more appropriate ED use. Of those
      who called ahead, 63% had an appropriate ED visit, compared with 61% of those who
      did not call ahead. Men were more likely to appropriately use the ED than women.
      Patients age > 64 were more likely to have appropriate ED visits than other age
      groups. CONCLUSIONS: We found no relationship between calling ahead and
      appropriate ED use. Possible explanations include that resident physicians are
      inexperienced and may be uncomfortable with telephone triage due to a lack of
      formal telephone management training. Patients may misrepresent the severity of
      their illness. Further, a patient who wants to be seen after hours must be seen
      for medical legal reasons. Interestingly, privately insured or Medicare
      recipients were more likely to use the ED appropriately. This association may
      suggest that fiscal accountability contributes to appropriate utilization, a
      scenario likely to change as managed care organizes Medicaid and indigent
      patients.

PMID- 9568497
TI  - Family practice residency program sites on the World Wide Web.
AB  - BACKGROUND AND OBJECTIVES: The World Wide Web is a rapidly expanding entity, and
      family practice residencies have begun using this technology through the
      development of Web sites. Our objective was to survey Web sites devoted to family
      practice residencies. METHODS: We sent a national survey to 451 family practice
      residency directors. RESULTS: Of 241 returned surveys, 113 residencies reported
      an existing Web site. Seventy-four percent of Web sites were created by faculty,
      but 31% also involved residents in creation. Resident recruitment was the most
      successful goal of Web sites; 42% of programs reported "moderate" to "very
      successful" results. However, most programs reported that it was too early to
      evaluate the goals listed in the survey. CONCLUSIONS: Family practice residencies
      have an increasingly significant presence on the Web. The development, content,
      and goals of the sites are similar across programs regardless of creation date,
      but the evaluation of the success of these goals is at an early stage for most
      programs.

PMID- 9568498
TI  - A comparison of family medicine clerkship student performance across multiple
      teaching sites.
AB  - BACKGROUND AND OBJECTIVES: Family medicine clerkships are frequently conducted in
      decentralized settings. Concerns have been raised regarding the educational
      consistency of such rotations. In this study, we assess learning across multiple
      training sites, as reflected by measures of student performance. METHODS: The
      study population was 77 students assigned to six clusters of family medicine
      clerkship training sites during the 1993-1994 academic year. Learning, as
      measured by faculty evaluations, objective structured clinical examination (OSCE)
      performance, and Society of Teachers of Family Medicine (STFM) predoctoral
      examination performance, was compared for student cohorts assigned to each of the
      teaching site clusters using analysis of variance. RESULTS: No differences in
      OSCE or STFM examination performance were found across the teaching site
      clusters. Greater variation in faculty evaluation across sites was apparent, and
      when the academic and private practice teaching sites were compared with the HMO
      and community clinics teaching sites, this variation achieved statistical
      significance. CONCLUSIONS: As measured by OSCE and STFM examination performance,
      student learning did not vary across multiple training sites. However, greater
      variability was found in faculty evaluations of student performance. Sources of
      this variation might include differing levels of student-faculty interactions
      across sites or subjectivity inherent to the faculty evaluation process.

PMID- 9568499
TI  - Survey of curriculum on homosexuality/bisexuality in departments of family
      medicine.
AB  - BACKGROUND AND OBJECTIVES: This study assesses what US departments of family
      medicine are doing to teach undergraduate medical students about
      homosexuality/bisexuality and the care of gay, lesbian, and bisexual patients.
      METHODS: A two-page, 14-item, self-administered questionnaire was sent to
      predoctoral directors at all US medical schools with departments of family
      medicine (n = 116). The questionnaire asked about teaching methods and curriculum
      hours, whether other departments address the topic, and if there is a
      gay/lesbian/bisexual student group at the medical school. RESULTS: Of the 116
      predoctoral directors surveyed, 95 (82%) responded. The mean number of
      departmental curriculum hours devoted to this topic was 2.5 hours for all 4 years
      of undergraduate medical school. About half (50.6%) of respondents reported that
      their department spent zero hours teaching about homosexuality/bisexuality. There
      were no differences in time spent by geographic region, size of school, or
      between public and private institutions. The most frequently cited teaching
      method was lectures in medical ethics, followed closely by lectures in human
      sexuality. CONCLUSIONS: About half of the responding family medicine departments
      did not include this topic in their curricula. Homosexuality/bisexuality should
      be included in family medicine's curriculum to ensure that future primary care
      physicians can properly care for all of their patients. Recommendations for
      curriculum modifications are provided.

PMID- 9568500
TI  - Family practice residency programs and the graduation of rural family physicians.
AB  - BACKGROUND AND OBJECTIVES: Family practice residency programs graduate about 600
      rural physicians each year. Increases in resident positions have not increased
      the numbers who choose rural practice. This study examines the relationship
      between program characteristics and the graduation rate of rural physicians.
      METHODS: From 1994-1996, we sent an annual survey to the directors of all
      nonmilitary family practice residency programs; 353 programs (96% response rate)
      returned questionnaires. Weighted least-squares regression was used to analyze
      the relationship between program factors and the percentage of graduates who
      chose practices in 1992, 1993, and 1994 in towns of less than 25,000 not adjacent
      to a larger metropolitan area. RESULTS: Family practice residency programs that
      graduated more rural physicians had more required rural and obstetrical training
      months, had a full or partial rural mission, were located in more rural states,
      had the program director as the rural contact, had a procedural emphasis, had
      fewer residents who were minorities or female, and used fewer types of other
      major graduate programs for rotations. CONCLUSIONS: This study outlines the
      important contribution of rural emphasis and training in family practice
      residency programs. Future studies should explore rural, procedural, and
      obstetrical training interventions and examine gender, minority, and program
      location issues.

PMID- 9568501
TI  - Management of spontaneous abortion in family practices and hospitals.
AB  - BACKGROUND AND OBJECTIVES: We performed two retrospective chart surveys, the
      first of 200 consecutive hospital emergency visits for spontaneous abortion and
      the second in 33 family physicians' offices examining 245 patients with
      spontaneous abortions. This study determined the rate of surgical management of
      spontaneous abortions within family practices and hospitals, as well as the rate
      of referrals and complications. METHODS: In the retrospective chart surveys, the
      information collected included the number of spontaneous abortions, dilation and
      curettages (D&Cs), referrals, and complications. RESULTS: Of the women presenting
      to the hospitals, 92.5% had D&Cs, while 51% of the women presenting to family
      physicians had D&Cs. Of the women presenting to the hospitals, 99.5% were
      referred to gynecologists, compared with 41% of the family practice patients.
      Hemorrhage occurred in 4.6% of the hospital patients and 2% of the family
      practice patients. Infection occurred in 6% of the hospital patients and .8% of
      the family practice patients. CONCLUSIONS: Patients with spontaneous abortions
      who saw their family physicians were more likely to be managed conservatively
      than those seen in the hospitals. There was no increase in complications in the
      conservatively managed patients.

PMID- 9568502
TI  - Host/environment medicine: a family practice model for the future.

PMID- 9568503
TI  - Diagnostic telepathology.

PMID- 9568504
TI  - Immunoperoxidase staining for cytokeratins 8 and 18 is very sensitive for
      detection of occult node metastasis of colorectal cancer: a comparison with
      genetic analysis of K-ras.
AB  - AIMS: Recent reports suggest that genetic examination of K-ras or p53 mutation is
      more sensitive for the detection of occult lymph node metastasis in colorectal
      carcinomas than conventional examination by haematoxylin and eosin (H & E)
      staining or immunohistochemistry for gene products. The aim of this study was,
      first, to define the microscopic characteristics of metastatic cancer cells in
      lymph nodes stained by the anti-cytokeratin antibody CAM5.2 for cytokeratins 8
      and 18, and, second, to compare the detection rate of occult lymph node
      metastasis for immunohistochemical vs genetic methods. METHODS AND RESULTS: K-ras
      mutations were first examined in primary tumours of seven cases which showed
      distant metastasis or local recurrence within 5 years of the initial surgery in
      spite of the original reporting of no lymph node metastasis by routine H & E
      staining. K-ras mutations were positive in three cases in primary tumours and
      lymph nodes, and the remaining four primary tumours were negative for p53
      mutation as well as K-ras mutation. Therefore, genetic analysis of occult lymph
      node metastasis was uninformative, but occult metastasis was detected by
      cytokeratin staining in two of these four cases. Comparative study of cytokeratin
      positive cells was performed on each of the 43 lymph nodes from three cases with
      K-ras mutations. Cancer cells were detected in 28 of the 43 lymph nodes (65.1%)
      by cytokeratin staining and in 10 of the 43 corresponding lymph nodes (23.3%) by
      genetic analysis. Artefactual contamination by cancer cells was present in eight
      of the 28 cytokeratin positive lymph nodes, and three of the eight nodes were
      genetically positive. CONCLUSIONS: This study suggests that cytokeratin
      immunohistochemistry is more sensitive and specific for the detection of occult
      lymph node metastasis than genetic diagnosis by K-ras mutation in cases with
      genetic alterations as well as in cases without them.

PMID- 9568505
TI  - E-cadherin and calretinin: a useful combination of immunochemical markers for
      differentiation between mesothelioma and metastatic adenocarcinoma.
AB  - AIMS: To assess the diagnostic accuracy of combinations of antibodies in the
      differential diagnosis of metastatic carcinomas and mesotheliomas in pleural
      lesions. METHODS AND RESULTS: The specificity and sensitivity of the commercially
      available antibodies Ber-EP4, MOC-31, CEA, B72.3, CD15, E-cadherin and calretinin
      were evaluated using an indirect immunoperoxidase staining technique. This
      technique was applied to formalin-fixed, paraffin-embedded tissue blocks of
      pleural lesions. Twenty-one patients with metastatic carcinoma (MC) and 20
      patients with malignant mesothelioma (MM) were included. The combination E
      cadherin/calretinin had the highest specificity (MC 100% and MM 91%) and
      sensitivity (MM 100% and MC 91%) considering both categories of tumours.
      CONCLUSIONS: The combination of E-cadherin/calretinin appears to be a suitable
      panel for distinguishing metastatic carcinomas and mesotheliomas in pleural
      lesions. The additional value of other markers is limited.

PMID- 9568506
TI  - Vascular density does not predict future metastatic disease in clinical stage 1
      non-seminomatous germ cell tumours of the testis.
AB  - AIM: This study aimed to determine whether patients with stage 1 testicular non
      seminomatous germ cell tumours (NSGCT) with high vascular density have a greater
      risk of disease recurrence than those with a low vascular density. METHODS AND
      RESULTS: Orchidectomy specimens from 42 patients with stage 1 NSGCT, treated by
      orchidectomy and surveillance alone, were studied. Vessel density was counted in
      tumour sections immunohistochemically stained for CD34. The mean of the three
      highest counts (x250, field size 0.67 mm2) for each tumour was used. Tumour
      vessel density was very similar for relapsing and non relapsing patients.
      Vascular invasion was the only variable significantly predictive of disease
      recurrence at 2 years post-orchidectomy (P = 0.025). There was wide variation of
      vessel counts between different blocks of a tumour, compared with interobserver
      variation. The tumour tissue type in the area of highest vessel density was
      embryonal carcinoma in 50% and teratoma (mature or immature) in 38%. CONCLUSIONS:
      We confirmed the value of vascular invasion as a prognostic marker in stage 1
      NSGCT. Tumour vessel density was of no prognostic value. Two factors may
      contribute to this. First, there was wide variation of vessel density between
      different blocks of a tumour. Second, the most vascular area in a tumour was
      frequently in low-grade tumour.

PMID- 9568507
TI  - Pulmonary giant cell carcinoma: pathological entity or morphological phenotype?
AB  - AIMS: To evaluate the morphological spectrum and clinical significance of giant
      cell carcinoma and to assess the frequency of tumour giant cell production in a
      consecutive series of primary (non-giant cell) lung tumours. METHODS AND RESULTS:
      Forty-six cases of giant cell carcinoma of the lung were collated from two
      centres over a 12-year period. Giant cell carcinoma was found to be associated
      with areas of clear cell carcinoma, spindle cell carcinoma and showed
      trophoblastic differentiation (syncytiotrophoblastic giant cells and beta-human
      chorionic gonadotrophin immunopositivity) in 57%, 34% and 26% cases,
      respectively. 'Pure' giant cell carcinoma was identified in five (11%) cases.
      Eleven of the tumours contained diastase-resistant periodic acid-Schiff positive
      material and were separately designated as giant cell adenocarcinomas. Areas of
      squamous cell and neuroendocrine differentiation (as determined by chromogranin A
      and Leu-7 immunopositivity) were not found. The median survival for giant cell
      carcinoma (excluding the giant cell adenocarcinomas) was 18 months. Median
      survival was not adversely affected by the extent of tumour giant cell formation
      or by the presence of trophoblastic differentiation. Of 200 consecutive non-small
      cell lung carcinomas, tumour giant cells constituting < 10% of the tumour were
      identified in 32% of adenocarcinomas and 26% of squamous cell carcinomas.
      CONCLUSIONS: The presence of tumour giant cells in lung carcinoma does not, in
      itself, indicate a more aggressive tumour type, Giant cell carcinoma of the lung
      does not appear to be a distinct entity but a morphological phenotype expressed
      by a heterogenous group of tumours. We support and advocate the use of an
      encompassing term such as 'pleomorphic' or 'anaplastic' carcinoma for those
      tumours showing no specific differentiation pattern but which express diverse
      morphological features such as giant cell formation, clear or spindle cell
      change.

PMID- 9568508
TI  - Maintenance of polarity and a dual cell population in adenoid cystic carcinoma of
      the breast: an immunohistochemical study.
AB  - AIMS: Adenoid cystic carcinoma (ACC) of the breast, although quite uncommon, is
      histologically distinct and has an excellent prognosis. Our purpose was to
      characterize molecular markers of cellular differentiation and polarity to define
      better the role that these combined features might play in the excellent
      prognosis of ACC in this site. METHODS AND RESULTS: We performed
      immunohistochemical stains for expression of vimentin (VM), cytokeratin (CK),
      smooth muscle actin (SMA), laminin (LAM), E-cadherin (E-cad), beta-catenin (beta
      cat) and fodrin in 14 examples of ACC. Two types of intercellular lumens and
      defining lining cells were detected: true epithelial lumens were lined by CK
      positive cells that maintained the normal glandular luminal cells with an intact
      polarity and basolateral membrane compartment indicators: fodrin, E-cad and beta
      cat. The second type of intercellular space was a pseudolumen, surrounded by
      myoepithelial cells that were strongly positive for VM and SMA, and lined by LAM.
      Double staining for VM and CK, VM and SMA, and CK and SMA detected occasional
      cytoplasmic co-expression of these markers in the myoepithelial cell compartment,
      but VM and SMA did not stain epithelial lumenal cells. CONCLUSIONS: ACC of the
      breast is characterized by the presence of two types of intercellular lumens, one
      conserving basolateral markers of normal polarity (epithelial) with the other
      containing basement membrane material (abutted by myoepithelial cells). Dominance
      of VM staining may be a hallmark of ACC, along with maintained epithelial and
      myoeithelial compartments. This status of advanced, normal differentiation
      despite local invasion may be responsible for lack of distant metastasis.

PMID- 9568509
TI  - Myoepithelial carcinoma (malignant myoepithelioma): first report of an occurrence
      in the maxillary sinus.
AB  - AIM: We document for the first time the occurrence of a malignant myoepithelioma
      at a site other than within the major and minor salivary glands. METHODS AND
      RESULTS: A 67-year-old male presented with progressive symptoms and signs of a
      space-occupying lesion in the right maxillary sinus. An initial biopsy identified
      a malignant (myo)epithelial lesion and a radical maxillectomy was performed.
      Histology, supplemented by immunohistochemistry, confirmed the presence of a
      malignant myoepithelioma. CONCLUSION: Malignant myoepithelioma is a very rare
      tumour composed almost exclusively of myoepithelial cells and, to date, has only
      been described arising in the the major and minor salivary glands. A variety of
      tumours of salivary tissue have been reported within the head and neck area at
      sites outside the major and minor salivary glands, probably arising within
      accessory salivary tissue. We report the first case of a malignant myoepithelioma
      occurring in the maxillary sinus, also presumably arising in accessory salivary
      tissue in this location.

PMID- 9568510
TI  - Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical
      study of 15 cases.
AB  - AIMS: Intraosseous jaw cysts with a solely orthokeratinized lining epithelium
      have been suggested to differ from the typical odontogenic keratocysts (OKC) by
      exhibiting a less aggressive behaviour. We report 15 cases of such cyst type
      under the term of 'orthokeratinized odontogenic cyst (OOC)' and compared their
      clinical, histological and immunocytochemical features with that of OKC. METHODS
      AND RESULTS: The cysts of the present series were all solitary lesions, occurred
      mostly in young male patients, and showed a predilection for the posterior
      mandible areas. Follow-up of 14 patients, nine of whom were treated by simple
      enucleation, revealed no recurrence over a period of 3.5-12 years after surgery.
      None of the patients had any association with the naevoid basal cell carcinoma
      syndrome. Furthermore, histological and immunocytochemical comparison between OOC
      and OKC revealed marked differences in their morphology and epithelial
      expression. The lining epithelium of OOC lacked the typical features of OKC and
      appeared to show a lower proliferative activity. CONCLUSION: These findings
      suggest that OOC is clinicopathologically separate from other types of
      odontogenic cysts and may thus constitute a distinct clinical entity.

PMID- 9568511
TI  - Localization of the cellular expression of inhibin in trophoblastic tissue.
AB  - AIMS: Inhibin is a peptide hormone which is normally produced by ovarian
      granulosa cells and which inhibits the release of follicle stimulating hormone
      from the pituitary gland, thus acting as a modulator of folliculogenesis. Serum
      inhibin levels are higher during pregnancy than during the normal menstrual cycle
      and the placenta is thought to be a source of circulating inhibin. Previous
      studies have yielded conflicting results as to the cellular localization of
      inhibin in the placenta and the aim of the present study was to investigate the
      immunohistochemical localization of the hormone in placental tissue. We also
      wished to investigate whether inhibin could be demonstrated in choriocarcinoma
      and in non-gestational trophoblastic tissue. MATERIALS AND RESULTS:
      Immunohistochemical staining was performed using a monoclonal antibody against
      the alpha subunit of human inhibin. Specimens included in the study were
      intrauterine products of conception (n = 36), extrauterine products of conception
      (n = 4), decidualized endometrium (n = 15), extrauterine decidualized tissue (n =
      3), hydatidiform mole (n = 5), uterine choriocarinoma (n = 2) and testicular
      embryonal carcinoma with syncytiotrophoblast giant cells (n = 6). In cases of
      products of conception, including hydatidiform mole, there was consistent strong
      positive staining of syncytiotrophoblast but no staining of cytotrophoblast with
      anti-inhibin. Staining with anti-inhibin highlighted trophoblastic cells within
      the placental bed. In a small number of cases there was focal weak positive
      staining of decidua. There was positive staining of the two cases of uterine
      choriocarcinoma and of syncytiotrophoblast giant cells in the six cases of
      testicular embryonal carcinoma. CONCLUSIONS: The study shows that
      immunohistochemically detectable inhibin alpha subunit in placental tissue is
      mainly localized within syncytiotrophoblast although in some cases there is also
      positive staining of decidua. Production of inhibin by these cells may account
      for raised serum levels during pregnancy. Inhibin can also be demonstrated in
      choriocarcinoma and in nongestational trophoblastic tissue. Inhibin is a
      sensitive marker of syncytiotrophoblast and staining with this antibody may prove
      useful in the diagnosis of choriocarcinoma and in the demonstration of
      trophoblastic cells in germ cell tumours.

PMID- 9568513
TI  - Phenotypic diversity of neurofibromatosis 2: association with plexiform
      schwannoma.
AB  - AIMS: Plexiform schwannoma (PS) is a rare variant of benign schwannoma
      characterized by a multinodular and plexiform growth pattern. In contrast to
      plexiform neurofibroma. PS is not associated with neurofibromatosis 1 (NF-1; von
      Recklinghausen's disease) and has no propensity for malignant transformation. The
      purpose of this study was to clarify the relationship between PS and the entities
      of neurofibromatosis 2 (NF-2; bilateral acoustic neurofibromatosis) and
      schwannomatosis. METHODS AND RESULTS: Six cases of PS associated with NF-2 or
      meningioma were retrospectively studied clinicopathologically and
      immunohistochemically. Four cases of PS were found among the patients with NF-2,
      and all of these had multiple PSs; three cases also had multiple schwannomas of
      the spinal nerve roots and two of these had meningioma. Two other patients had
      meningioma, but not NF-2. Four patients were male and two were female. The ages
      ranged from 18 to 52 years (mean 29.6 years). Histologically, PS showed the
      histological features that have been previously described, i.e. schwannoma
      composed of a predominant Antoni A-type component with a plexiform growth
      pattern. Immunohistochemically, the tumour cells were positive for S100 protein.
      Each nodule was surrounded by perineural cells which were positive for epithelial
      membrane antigen. CONCLUSIONS: It is important to recognize that PS could be
      associated with NF-2 or meningioma. The combination of PS and meningioma may be a
      'formes frustes' of NF-2, and is clinically overlapped with schwannomatosis.

PMID- 9568512
TI  - Affinity of four lectins for endocervical and endometrial non-neoplastic and
      neoplastic glandular epithelium.
AB  - AIMS: Endocervical and endometrial tissues were stained with four lectins to
      determine the difference in staining pattern between non-neoplastic and
      neoplastic conditions of these tissues. METHODS AND RESULTS: The lectins used
      were Ulex europaeus agglutinin (UEA), Dolicho biflorus agglutinin (DBA).
      Concanavalin A (Con A), and Phaseolus vulgaris agglutinin (PHA). Endocervical
      tissues included normal endocervical glands, microglandular hyperplasia, minimal
      deviation adenocarcinoma and endocervical adenocarcinoma, well to poorly
      differentiated types. Endometrial tissues were collected from normal endometrium,
      simple glandular hyperplasia, complex hyperplasia, atypical hyperplasia and
      adenocarcinoma grades 1-3. Non-neoplastic and neoplastic endocervical and
      endometrial glandular epithelium showed positive reaction for UEA, Con A and PHA.
      Non-neoplastic glands showed mild to moderate intensity and apical and/polar type
      of staining pattern for all lectins. Endocervical adenocarcinoma including
      minimal deviation adenocarcinoma (MDC) and adenocarcinoma well to moderately
      differentiated type showed diffuse cytoplasmic type of staining pattern for all
      lectins, but poorly differentiated adenocarcinoma of endocervix showed only a
      stromal pattern for all lectins. Endometrial hyperplasia and adenocarcinoma
      grades 1-3 showed positive reaction for all lectins except for DBA. The staining
      pattern of endometrial hyperplasia was variable, but adenocarcinoma grades 1-3
      showed diffuse type. CONCLUSION: Intensity and staining patterns of lectins are
      helpful in distinguishing between endocervical and endometrial non-neoplastic and
      neoplastic lesions. Intense positive reaction of MDC, especially for Con A and
      PHA, can differentiate this lesion from normal endocervical glands. The stromal
      type of staining pattern of poorly differentiated endocervical adenocarcinoma can
      also have diagnostic significance. Negative reactions of DBA lectin for
      endometrial adenocarcinoma can be used for differentiating it from endocervical
      adenocarcinoma.

PMID- 9568515
TI  - Controversies in MALT lymphoma classification, low and high grade.

PMID- 9568514
TI  - Primary intestinal gamma-delta T-cell lymphoma with evidence of Epstein-Barr
      virus.
AB  - AIMS: Primary intestinal T-cell lymphomas account for about 5% of all primary
      gastrointestinal lymphomas and are mostly associated with coeliac disease. They
      usually express the CD3-associated T-cell receptor alpha/beta heterodimer and
      HML1, and some are related with Epstein-Barr virus (EBV). As far as we know, the
      present report describes the first case of primary gamma-delta (gamma delta) EBV
      associated intestinal T-cell lymphoma without enteropathy. Only hepatosplenic,
      nasal and cutaneous gamma delta T-cell lymphomas have previously been described.
      METHODS AND RESULTS: Our case concerned a 43-year-old man with no history of
      coeliac disease, who presented with multifocal small bowel involvement showing
      high grade T-cell lymphoma with medium sized and large pleomorphic cells and a
      small pleomorphic T-cell component. Angioinvasion and angiocentricity were
      occasionally present. Immunohistochemical studies of lymphoma cells showed a T
      cell gamma delta phenotype (CD3+, CD2+, TCR delta 1+, V delta 2+ and beta F1-)
      without expression of CD4, CD8, CD5, or HML1. Most tumour cells were positive for
      the cytotoxic granular proteins TiA1 and granzyme B. Rearrangement of the TCR
      gamma chain gene was demonstrated by polymerase chain reaction and in-situ
      hybridization with EBER probes revealed strong nuclear positivity in virtually
      all neoplastic cells. CONCLUSION: We described the first case of primary
      intestinal gamma delta T-cell lymphoma without enteropathy in which EBV might
      fulfil a pathogenic role.

PMID- 9568516
TI  - Proliferation in adenomyoepitheliomas.

PMID- 9568517
TI  - Middle ear adenoma.

PMID- 9568518
TI  - Dissecting aneurysm of the pulmonary artery associated with facial cavernous
      haemangioma.

PMID- 9568519
TI  - Primary amyloidosis complicated by systemic necrotizing arteritis.

PMID- 9568520
TI  - Composite phaeochromocytoma-ganglioneuroblastoma in a patient with multiple
      endocrine neoplasia type IIA.

PMID- 9568521
TI  - Gastric 'pseudolipomatosis'.

PMID- 9568522
TI  - Transitional cell carcinoma of the endometrium.

PMID- 9568523
TI  - Pseudo-malignant laryngeal nodule (inflammatory myofibroblastic tumour)

PMID- 9568524
TI  - The epidemiology of erectile dysfunction and its risk factors.
AB  - Erectile dysfunction (ED) affects millions of men throughout the world. The
      literature is ample, but an accurate estimate of its prevalence is still
      difficult since figures mainly refer to the USA, and are based mostly on small
      selected samples of people. Caution must anyway be used in comparing data from
      studies conducted in the past because of possible differences in the definition
      and classification of ED. Many factors are believed to contribute to the
      development and maintenance of ED. The influence of age and of several medical
      conditions (diabetes, vascular disease, and chronic diseases such as hepatic
      failure, renal failure and dialysis) is well defined. Also well documented is the
      role of some drug groups, whereas the role of other pharmacological agents is
      still controversial because of the frequent coexistence of other pathological
      conditions or concomitant exposure to other drugs. Less well defined and
      sometimes controversial is the role of risk factors mainly related to life-style
      such as cigarette smoking, alcoholism, total cholesterol levels and certain types
      of trauma. This paper reviews the main data on the epidemiology of ED and some
      related risk factors.

PMID- 9568525
TI  - Experimental uremia in male rats: effect of interval between partial
      nephrectomies on testicular function.
AB  - Testicular function in stepwise-nephrectomized rats, with a different interval
      between the two operations, was studied suing male Wistar rats. Serum levels of
      urea nitrogen and creatinine in stepwise-nephrectomized rats were significantly
      elevated compared to those in sham-operated rats (p < 0.001). With a 1-day
      interval between the two operations, these concentrations were considerably
      higher (p < 0.001) than those in 7-day interval rats. While serum LH levels were
      significantly reduced (p < 0.001) in 1-day interval rats, FSH levels in this
      group were considerably higher (p < 0.001) than in other groups. Serum
      concentrations of androstenedione in 1-day interval rats were significantly
      suppressed compared to other groups (p < 0.01). Serum testosterone levels in
      stepwise-nephrectomized rats were considerably lower (p < 0.001) than in sham
      operated rats. It is assumed that testicular function in stepwise-nephrectomized
      rats is influenced by the interval between the two operations.

PMID- 9568526
TI  - Increased testosterone production in vitro by Leydig cells from rats with severe
      autoimmune orchitis.
AB  - We have previously observed (M. O. Suescun et al., 1994, Journal of Andrology,
      15, 442-448) that rats with autoimmune orchitis (EAO) exhibit increased
      testosterone production in vitro by isolated testes. The aim of the present study
      was to determine whether the increase in testosterone production correlated with
      an enhanced number of Leydig cells and/or enhanced steroidogenic capacity per
      Leydig cell. For this purpose, EAO was induced in adult Sprague-Dawley rats by
      active immunization with testicular homogenate and adjuvants. At 80 days after
      the primary immunization, 60% of rats presented with severe testicular damage
      characterized by sloughing of the seminiferous epithelium, seminiferous tubule
      atrophy and interstitial mononuclear cell infiltration. At 160 days after the
      first immunization, testicular lesions were more severe. A morphometric study, by
      light microscopy, showed an increase in the number of Leydig cells in rats with
      EAO (45% increase at 80 days and 50% at 160 days). By electronmicroscopy,
      testicular sections of rats with EAO revealed the presence of numerous Leydig
      cells closely associated with macrophages. Most Leydig cells exhibited
      ultrastructural features of active steroid secreting cells. The steroidogenic
      capacity of Percoll-purified Leydig cells from tests of rats with EAO, killed at
      80 and 160 days, was evaluated. Leydig cells from rats with EAO exhibited an
      enhanced steroidogenic response to hCG in vitro at 80 days (38%) and an increase
      in basal (77%) and post-hCG testosterone production (115%) at 160 days compared
      to controls. However, these cells were less sensitive to hCG. In conclusion, the
      results indicate that the enhancement of in-vitro testosterone production
      observed in rats with EAO is accounted for both by the increased number of Leydig
      cells and by the increased testosterone production of each Leydig cell.

PMID- 9568527
TI  - Toxicity of ornidazole and its analogues to rat spermatozoa as reflected in
      motility parameters.
AB  - Ornidazole, a 5-nitro-imidazole derivative, has contraceptive properties in rats.
      As some ornidazole passes through the body unmetabolized after administration,
      the aim of this study was to investigate if ornidazole itself has a direct effect
      on sperm motility and whether these effects are limited or potentiated by the
      epididymal epithelium or structural changes to the molecule. Cauda epididymal
      spermatozoa or cauda epididymal tubules were incubated with ornidazole or
      ornidazole analogues, and motility parameters were subsequently measured by means
      of a computer-assisted sperm analysis (CASA) system. Incubation of spermatozoa in
      2.5 mmol/L ornidazole for 4 h reduced their motility significantly, whereas
      incubation of epididymal tubules for 8 h in 10 mmol/L ornidazole was required to
      alter the velocity parameters of the enclosed spermatozoa upon release,
      suggesting that extratubular non-metabolized ornidazole can participate in
      inhibiting the motility in vivo. The in vitro toxicity of ornidazole derivatives
      depends on the halogen present and on the position of the nitro-group. The
      putatively inactive (R)- and the active (S)-ornidazole exhibited equivalent
      depression of sperm motility by direct incubation. This observation, and the
      differences between the in vitro and the in vivo efficacies of various ornidazole
      analogues, indicates distinct mechanisms of motility inhibition in the two
      experimental systems.

PMID- 9568528
TI  - Effects of vasoactive intestinal peptide (VIP) on the testicular vasculature of
      the rat.
AB  - Using laser Doppler flowmetry, the effects of unilateral intratesticular
      injection of vasoactive intestinal peptide (VIP) on testicular blood flow and
      mean arterial blood pressure were studied in anaesthetized adult rats. At doses
      of 50 and 500 ng, VIP increased blood flow by 29 +/- 8 and by 77 +/- 25% (p <
      0.05), respectively (means +/- SEM) at 5 mm, but not at 15 mm, from the injection
      site. Blood pressure was not significantly affected by 50 ng, but was slightly
      reduced (by -8 +/- 2%) after treatment with 500 ng VIP. The highest dose of VIP
      (5 micrograms) reduced blood pressure (by -30 +/- 9%), and decreased blood flow
      at 15 mm, but not at 5 mm, from the injection site. It is concluded that VIP can
      act as a vasodilator in the rat testis.

PMID- 9568529
TI  - A germ cell-specific nuclear antigen recognized by a monoclonal antibody raised
      against mouse testicular germ cells.
AB  - A monoclonal antibody (mAb TRA 104) raised against mouse testicular germ cells
      was able to recognize the nuclei of testicular germ cells at all the stages of
      differentiation from embryonic gonocytes to spermatids and did not react with any
      somatic cells. The antigen recognized by mAb TRA 104 was exclusively present in
      testicular extracts. The molecular weights and isoelectric point (pI) of the
      antigens determined by Western blotting analysis were 60-110 kDa and 7.2,
      respectively. This antigen(s) is referred to as a germ cell-specific nuclear
      antigen(s) (GENA) since GENA was first detected specifically in the genital ridge
      at around 12 days of gestation by Western blotting analysis. In the testis, the
      expression increased gradually until adulthood whereas it was lost in the ovary
      by postpartum day 5. Thus, GENA is a molecule(s) exclusively present in the
      nuclei of germ cells and may be a useful marker with which to study the mechanism
      of germ cell development and differentiation at the molecular level.

PMID- 9568530
TI  - Sperm morphology assessment: diagnostic potential and comparative analysis of
      strict or WHO criteria in a fertile and a subfertile population.
AB  - This prospective study compared the diagnostic and predictive potential of sperm
      morphology assessments in a fertile vs. a subfertile population, evaluated in
      three different laboratories. The fertile population included 144 men who had
      recently fertilized their partners. As subfertile controls, 136 men with a
      history of subfertility for more than 12 months were used. All semen samples
      (280) were evaluated in three different centres in a blind fashion, without any
      patient information. The evaluation of sperm morphology was performed according
      to the criteria normally used in the different laboratories: WHO (1992) criteria
      for laboratory A, and Tygerberg strict criteria for laboratories B and C. Using
      ROC analysis, the predictive power of sperm morphology turned out to be different
      in the three laboratories (area under ROC curve: 69% for lab A, 72% for lab B and
      78% for lab C). Using percentile 10 of the fertile population as the cut-off
      value for normality, we obtained the following results: 2, 1 and 5% for
      laboratories A, B and C, respectively. Using ROC analysis cut-off values with
      optimal specificity and sensitivity were 6, 1 and 10%, respectively. Although our
      data highlight a reasonable predictive power of sperm morphology in centres using
      different or the same criteria, cut-off values for normality were different, even
      when the same criteria were applied. These results stress the importance of
      standardization in sperm morphology evaluation and the need for examining a
      reference population in estimating the real threshold value in different
      laboratories.

PMID- 9568531
TI  - In vivo analysis of germ cell apoptosis reveals the existence of stage-specific
      'social' control of germ cell death in the seminiferous epithelium.
AB  - It has become clear in recent years that programmed cell death is regulated
      during development by signals from other cells. Nevertheless, compared to the
      'social' control of cell proliferation, relatively little is known about the
      'social' control of cell death in other systems. Since in a previous study we
      showed that induced germ cell apoptosis occurs at specific stages of the
      spermatogenic cycle, in this study we aimed to ascertain the existence of
      supracellular control of germ cell death during spermatogenesis. Therefore, the
      TUNEL technique has been used to analyse whether all of the different germ cell
      types are induced to die at these specific stages in animals injected
      intratesticularly with one of several inducers of apoptosis. Our findings suggest
      that all of the investigated agents trigger apoptosis in all the diverse
      progenies of germ cells existing at stages I, XII or XIV of the spermatogenic
      cycle. In contrast, at most other stages the number of apoptotic cells was
      similar to that found in control animals. These data are consistent with the
      existence of an intercellular control of germ cell death during spermatogenesis.
      We conclude that the seminiferous epithelium provides a suitable in vivo model to
      study the mechanisms underlying the 'social' control of apoptosis.

PMID- 9568532
TI  - Cholinergic immunolesions by 192IgG-saporin--useful tool to simulate pathogenic
      aspects of Alzheimer's disease.
AB  - Alzheimer's disease, the most common cause of senile dementia, is characterized
      by intracellular formation of neurofibrillary tangles, extracellular deposits of
      beta amyloid as well as cerebrovascular amyloid accumulation and a profound loss
      of cholinergic neurons within the nucleus basalis Meynert with alterations in
      cortical neurotransmitter receptor densities. The use of the cholinergic
      immunotoxin 192IgG-saporin allows for the first time study of the impact of
      cortical cholinergic deafferentation on cortical neurotransmission, learning, and
      memory without direct effects on other neuronal systems. This model also allows
      the elucidation of contributions of cholinergic mechanisms to the establishment
      of other pathological features of Alzheimer's disease. The findings discussed
      here demonstrate that cholinergic immunolesions by 192IgG-saporin induce highly
      specific, permanent cortical cholinergic hypoactivity and alterations in cortical
      neurotransmitter densities comparable to those described for Alzheimer's disease.
      The induced cortical cholinergic deficit also leads to cortical/hippocampal
      neurotrophin accumulation and reduced amyloid precursor protein (APP) secretion,
      possibly reflecting the lack of stimulation of postsynaptic M1/M3 muscarinic
      receptors coupled to protein kinase C. This immunolesion model should prove
      useful to test therapeutic strategies based on stimulation of cortical
      cholinergic neurotransmission or amelioration of pathogenic aspects of
      cholinergic degeneration in the basal forebrain. Application of the model to
      animal species that can develop beta-amyloid plaques could provide information
      about the contribution of cholinergic function to amyloidogenic APP processing.

PMID- 9568533
TI  - Comparison of glutamate and N-methyl-D-aspartate toxicities on rat mesencephalic
      primary cell cultures.
AB  - Excitotoxicities of glutamate and NMDA were studied on primary cultures of rat
      embryonic substantia nigra. The toxicity of the general neuronal population
      (identified with neuron specific enolase-NSE) was compared with that of
      dopaminergic neurons (identified with TH antibodies). We have shown that there
      exists a time-dependent toxicity to glutamate in 9 d old cultures in vitro and
      exposures as short as 5 min are significantly toxic. By comparing the effects of
      long time exposures (24 h) to NMDA and glutamate, we can show dose-dependent
      toxicity; however NMDA shows a less marked effect, especially at high doses (>
      500-1000 microM) as opposed to less potent lower doses (< 500 microM). In
      comparison to the general population of NSE-positive mesencephalic neurons, TH
      positive neurons seem to exhibit a similar vulnerability to EAA. The fact that TH
      positive neurons are only partially protected against glutamate toxicity by the
      non-competitive NMDA antagonist TCP indicates that they are more susceptible to
      non-NMDA mediated neurotoxicity than the general neuronal population.

PMID- 9568534
TI  - Selective activation by bryostatin-1 demonstrates unique roles for PKC epsilon in
      neurite extension and tau phosphorylation.
AB  - Phorbol esters such as 12-O-tetradeonyl phorbol-13 acetate (TPA) induce a time
      dependent biphasic effect on protein kinase C (PKC)-mediated events by fostering
      translocation of cytosolic (latent) PKC to the plasma membrane (where it is
      activated). Continued treatment, however, depletes the cell's entire PKC
      complement and induces a functional stake of PKC inhibition. Previous studies
      from several laboratories have demonstrated that long-term TPA treatment, like
      treatment with PKC inhibitors, induces neuronal differentiation. Bryostatin-1
      also induces translocation and overall downregulation of PKC following long-term
      treatment, yet, unlike TPA or PKC inhibitors, does not induce neuronal
      differentiation, promoting controversy regarding the role of PKC inhibition in
      neuronal differentiation. We demonstrate herein that, despite overall
      downregulation in human neuroblastoma cells, membrane-associated levels of one
      PKC isoform (PKC epsilon) are actually increased following long-term bryostatin-1
      treatment. Since previous studies have implicated this PKC isoform in
      phosphorylation of the microtubule-associated protein tau and in neuritogenesis,
      we examined the consequences of long-term bryostatin treatment on these
      phenomena. Treatment with 25 n-100 M bryostatin-1 for 72 h increased tau
      phosphorylation and inhibited neuritogenesis. By contrast, treatment with either
      TPA or the PKC inhibitor staurosporine did not induce tau phosphorylation and
      induced neurite elaboration. Bryostatin-1 antagonized neurite induction by
      staurosporine. These findings provide additional evidence for a unique role of
      PKC epsilon in the regulation of tau phosphorylation and neuronal
      differentiation, and demonstrate that bryostatin-1 can function under certain
      conditions as a selective PKC epsilon activator even following long-term
      treatment.

PMID- 9568535
TI  - Temporal pattern of plasminogen activator activity in the developing chick
      cerebellum.
AB  - Plasminogen activators are considered to be involved in several developmental
      events. The present work aims at characterizing the developmental pattern of
      expression of plasminogen activators in the chick cerebellum. Soluble fractions
      derived by ultracentrifugation from Triton X-100 treated membrane fractions were
      used for determination of the enzyme activity with a radial fibrinolytic assay.
      By using specific inhibitors and different anti-plasminogen activators antibodies
      it is shown that only one type of the enzyme, the urokinase-type plasminogen
      activator, is expressed during the cerebellum ontogeny. Our results show the
      existence of a bimodal pattern of enzyme activity with two peaks that temporally
      coincide with the processes of massive neuronal migration, neurite outgrowth and
      synapse formation and plasticity. It is proposed that plasminogen activator could
      play a role in these developmental events and that its pattern of variability is
      developmentally regulated.

PMID- 9568536
TI  - A transient CD15 immunoreactive sling in the developing mouse cerebellum.
AB  - The distribution of the 3-fucosyl-N-acetyl-lactosamine (FAL, CD15) epitope in the
      developing mouse cerebellum was examined with the aid of immunohistochemistry of
      paraffin sections. CD15 immunoreactivity first appeared at E15 as a discrete
      bundle of processes lying beneath, and slightly within, the deeper layers of the
      external granular layer. By E17, when the cerebellar anlagen had completed their
      midline fusion, these processes could be traced from the germinal trigone at the
      lateral limits of the cerebellar anlage around the posterior cerebellar midline
      to the opposite germinal trigone. By P2, this sling was no longer apparent and
      CD15 immunoreactivity was confined to astrocytes in the cerebellar white matter,
      surrounding the deep cerebellar nuclei. The CD15 immunoreactive processes pursue
      an unusual trajectory through the developing cerebellum, unlike any other
      previously described axonal or glial process bundle in the cerebellum. From its
      trajectory and association with the ventricular surface it seems that this
      structure, which we have named the transverse cerebellar sling, is composed of
      glial processes, although it was not immunoreactive for S-100 or glial fibrillary
      acidic protein. The transient appearance of this sling encircling the posterior
      cerebellum is suggestive of a role in prenatal cerebellar morphogenesis.

PMID- 9568537
TI  - C2H2-171: a novel human cDNA representing a developmentally regulated POZ
      domain/zinc finger protein preferentially expressed in brain.
AB  - We describe a novel human zinc finger cNDA. C2H2-171. This cDNA represents an
      mRNA which encodes a protein of 484 amino acids and a calculated molecular weight
      of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the
      protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar
      to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F,
      as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed
      in the brain, and increases during the course of murine development, with maximal
      expression in the adult. C2H2-171 RNA is differentially expressed in brain
      regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was
      expressed at high levels in primary cerebellar granule cell neurons compared to
      astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and
      maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location
      is associated with a number of cytogenetic aberrations including those involving
      brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171
      may play an important role in vertebrate brain development and function.

PMID- 9568538
TI  - Developmental expression of the NGF receptor p140trk in the septohippocampal
      system of the rat: a quantitative analysis.
AB  - An RNAse protection assay was used to identify p140trk mRNA in the developing rat
      septohippocampal system. In both the septum and hippocampus, levels of p140trk
      mRNA were low at birth and increased thereafter. Levels of transcripts were found
      to be much higher in the septum than in the hippocampus, whereas another brain
      region, the hypothalamus, showed levels of expression intermediate between these
      two structures. Only one isoform of the p140trk receptor was found to be
      expressed in the rat central nervous system (CNS) during development. This
      isoform corresponds to the one preferentially expressed in neural tissues in the
      adult animal. These data show that expression of the high affinity nerve growth
      factor (NGF) receptor is developmentally regulated during postnatal brain
      development and suggest that it might mediate NGF effects on developing central
      cholinergic systems.

PMID- 9568539
TI  - Relationship between the thymus and neurochemical changes in the hypothalamus
      preoptic area and prefrontal cortex in female rats with delayed puberty.
AB  - In female rats, aged 55-58 days with delayed puberty due to deficient growth and
      environmental stress, 5-hydroxyindoleacetic acid levels and serotonin turnover
      rate in the hypothalamus-preoptic area as well as body weight, body weight gain
      and relative weight of ovaries, uterus, adrenals and preputial glands were lower
      while serotonin and 5-hydroxyindoleacetic acid levels in the prefrontal cortex
      were higher when compared to normal rats with the latest onset of puberty aged 42
      52 days. In rats with delayed puberty, multiple regression analysis revealed a
      significant negative dependence on dopamine turnover in the hypothalamus-preoptic
      area for body weight gain and, of all organs, for the relative weight of the
      thymus. A similar negative significant dependence on serotonin turnover rate in
      the prefrontal cortex was also found for the relative weight of thymus and
      spleen. The same analysis in the opposite direction revealed a significant
      negative dependence of 3,4-dihydroxyphenylacetic acid levels and dopamine
      turnover rate in the hypothalamus-preoptic area as well as serotonin turnover
      rate in the prefrontal cortex only on thymus weight. After separation of delayed
      pubertal rats into two groups, based on absolute ovarian weight, the rats in the
      low ovarian weight range and no signs of puberty exhibited: lower body weight
      gain, lower body weight, and lower relative weight only of thymus, ovaries and
      preputial glands in parallel with an increased dopamine turnover rate in the
      hypothalamus-preoptic area and serotonin turnover rate in the prefrontal cortex
      compared to the delayed pubertal rats in the high ovarian weight range and early
      signs of puberty. The results suggest that in rats with delayed puberty: (1)
      serotonergic activation in the hypothalamus-preoptic area is lower compared to
      normal puberty rats; (2) dopaminergic activation in the hypothalamus-preoptic
      area negatively affects body weight gain, thymus weight and initiation of puberty
      and (3) thymus weight is negatively implicated in dopaminergic activation in the
      hypothalamus-preoptic area and serotonergic activation in the prefrontal cortex
      and positively related to ovarian weight and early signs of puberty.

PMID- 9568540
TI  - Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in
      particular.
AB  - The effect of eight different Chinese medicinal herbs (CMHs) on lymphocytes was
      studied in vitro using murine spleen cells. Among the studied eight CMHs,
      Astragalus membranaceus and Oldenlandia diffusa markedly stimulated murine spleen
      cells to proliferate. The responder cells for CMHs were B cells, because the
      response was depleted by the treatment of spleen cells with anti-immunoglobulin
      (i.g.) antibody and complement and after purification by nylon wool column. This
      response was not due to contamination by lipopolysaccharide (LPS), because CMHs
      could stimulate C3H/HeJ spleen cells which are low responders to LPS. CMHs
      enhanced the production of Ig. CMHs also enhanced the induction of allo-antigen
      specific cytotoxic T lymphocytes. However, CMHs had no effect on natural killer
      cells. Furthermore, CMHs stimulated macrophages to produce interleukin-6 and
      tumor necrosis factor. The electroelution of the proteins from SDS-PAGE gel
      showed that the active components of Oldenlandia diffusa had an apparent
      molecular weight of 90-200 kD and were sensitive to pronase E and NaIO4
      treatment, suggesting glycoproteins in nature. These results suggest that CMHs
      have immunomodulating activity in vitro and this activity could be used
      clinically for the modulation of immune responses.

PMID- 9568541
TI  - Echinacea-induced cytokine production by human macrophages.
AB  - Echinacea purpurea, a plant originally used by native Americans to treat
      respiratory infections, was evaluated for its ability to stimulate the production
      of cytokines by normal human peripheral blood macrophages in vitro. Commercial
      preparations of echinacea fresh pressed juice and dried juice were tested at
      concentrations ranging from 10 micrograms/ml to 0.012 microgram/ml and compared
      to endotoxin stimulated and unstimulated controls. Cytokine production was
      measured by ELISA after 18 h of incubation for IL-1 and 36 and 72 h for TNF
      alpha, IL-6, and IL-10. Macrophages cultured in concentrations of echinacea as
      low as 0.012 microgram/ml produced significantly higher levels of IL-1, TNF
      alpha, IL-6 and IL-10 (P < 0.05) than unstimulated cells. The high levels of IL
      1, TNF-alpha, and IL-10 induced by very low levels of echinacea are consistent
      with an immune activated antiviral effect. Echinacea induced lower levels of IL-6
      in comparison to the other cytokines measured. These results demonstrate the
      immune stimulatory ability of the unpurified fresh pressed juice of Echinacea
      purpurea and offer some insight into the nature of the resulting immune response
      as compared to endotoxin.

PMID- 9568542
TI  - In vitro effects of sho-saiko-to on production of granulocyte colony-stimulating
      factor by mononuclear cells from patients with chronic hepatitis C.
AB  - During the past 2 years, drug-induced interstitial pneumonia was reported in 66
      Japanese patients, mainly among chronic hepatitis C patients, undergoing
      treatment with the Japanese herbal medicine "Sho-saiko-to" (TJ-9). As
      interstitial pneumonia is also induced by granulocyte colony-stimulating factor
      (G-CSF), we examined the effects of TJ-9 on G-CSF production in peripheral blood
      mononuclear cells. In patients with hepatitis B or C, G-CSF production in the
      absence of any stimulation was significantly lower than healthy controls (p <
      0.01). G-CSF production increased along with the increase of TJ-9 levels, and
      this could induce excessive production of G-CSF in hepatitis C patients, and this
      may be a cause of interstitial pneumonia.

PMID- 9568543
TI  - Role of nitric oxide in the regulation of lymphocyte apoptosis and HIV-1
      replication.
AB  - Nitric oxide (NO) has been implicated in certain immunopathogenetic mechanisms
      during the course of infection with human immunodeficiency virus (HIV). We have
      evaluated the levels of NO release and lymphocyte apoptosis in peripheral blood
      mononuclear cell (PBMC) cultures from HIV-1 infected subjects and healthy
      controls. We have also examined these 2 parameters in parallel cultures
      maintained under conditions where either NO synthesis was inhibited or high level
      of NO was present. Nitrite contents in culture supernatants were measured as the
      stable end products of the released NO. Levels of spontaneous apoptosis and
      activation-induced cell death (AICD) by anti-CD3 or by phytohemagglutinin were
      evaluated using flow cytometry. Additional experiments were also aimed at
      addressing a potential link between NO synthesis and HIV-1 replication in human
      monocyte-derived macrophages (MDMs). Acutely infected MDMs with HIV-1Bal were
      maintained in culture, without any additional activation signal, for a period of
      14 days. Nitrites in the supernatants and mRNA accumulation of the inducible NO
      synthase (iNOS) in infected cells were assessed over the whole culture period. In
      addition, the effect of blocking NO synthesis during and after infection of MDMs,
      using an inhibitor of NO, was evaluated on the level of viral replication as
      measured by the presence of P24 antigen in the supernatants. Similarly, the
      effect on HIV replication of high NO levels in MDM cultures, supplied by a donor
      of NO during the 24 h period of infection, was also studied. We conclude that no
      elevation in NO release could be detected in PBMC cultures from HIV-1 infected
      subjects and that modulation of NO content may slightly regulate the level of
      spontaneous lymphocyte apoptosis but not that of AICD. Infection of MDMs with HIV
      1 does not seem to induce detectable NO release or iNOS mRNA accumulation.
      Similarly, neither inhibition of NO synthesis nor the presence of high NO levels
      during the infection period could modify the outcome of virus replication in
      macrophages.

PMID- 9568544
TI  - Erythrocyte-dependent mitogenic activity of epigallocatechin gallate on mouse
      splenic B cells.
AB  - We previously reported that epigallocatechin gallate (EGCg), the main constituent
      of tea catechins, displays mitogenic effect on mouse splenic B cells. During
      research into the mechanism(s), it was found that the mitogenic activity of EGCg
      was dependent on the presence of red blood cells (RBC). When RBC in T cell
      depleted spleen cells were removed, EGCg did not enhance the proliferation of B
      cells and even showed toxic effect at 25-50 micrograms/ml. When mouse, rabbit or
      sheep RBC as well as RBC-ghosts were added into the cultures, EGCg showed the
      mitogenic activity at a range of 1-50 micrograms/ml. Thereafter, we preincubated
      RBC with EGCg at 4 degrees C for various times and then washed the RBC to remove
      free EGCg in the suspensions. The EGCg-preincubated RBC also enhanced B cell
      proliferation. As short as ten minutes was sufficient for EGCg to bind to RBC
      membrane. These results indicate that EGCg first attached to the membrane of RBC
      and then stimulated B cell proliferation. The above results suggest an important
      immunoregulatory function of RBC.

PMID- 9568545
TI  - Evidence that eosinophil infiltration in the OK-432/fibrinogen-injected Meth-A
      tumor in mice is mediated by locally produced IL-5.
AB  - It was previously demonstrated that a single injection of OK-432 (a penicillin
      treated freeze-dried Streptococcus) mixed with fibrinogen into cancer tissues
      induces marked infiltration by eosinophils of the tumor stroma and leads to tumor
      necrosis. In the present study, we examined mechanisms regulating the local
      accumulation of eosinophils and the role of infiltrating eosinophils in tumor
      regression using the OK-432/fibrinogen injected Meth-A fibrosarcoma tumor. After
      injection of OK-432/fibrinogen into the tumor on the left flank of the BALB/c
      mice, eosinophil infiltration became obvious in the tumor stroma on day 3
      following the accumulation of macrophages and neutrophils, was massive on day 5
      and decreased by day 10. After the decrease in the infiltration of eosinophils,
      the tumor injected with OK-432/fibrinogen diminished markedly in size with
      ulceration as compared with control. Northern blot analysis revealed that
      expression of IL-5 mRNA in the tumor tissue was not detected on day 0, was
      significantly on day 3, reached the maximum on day 5, and thereafter decreased by
      day 10. Although intraperitoneal injection of rat anti-IL-5 monoclonal antibody
      in tumor bearing mice prior to OK-432 injection inhibited the infiltration of
      eosinophils, the antitumor effects of OK-432 persisted. In the blood, neither
      eosinophilia nor IL-5 activity was recognized during the course of the
      experiment. These results suggest that intratumoral injection of OK
      432/fibrinogen induces local production of IL-5, which in turn recruits
      eosinophils into the tumor tissue, however, the infiltrating eosinophils do not
      play an important role in tumor regression.

PMID- 9568546
TI  - Prothymosin alpha 1 effects in vitro on chemotaxis, cytotoxicity and oxidative
      response of neutrophils from melanoma, colorectal and breast tumor patients.
AB  - Immunoregulatory effects of thymic peptides on functions of polymorphonuclear
      leukocytes (PMNs) are poorly investigated. We studied the effects of prothymosin
      alpha 1 (Pro alpha 1) on PMNs from patients with colorectal tumors, breast tumors
      and melanoma (total n = 37) in comparison with healthy donors (n = 18), with
      respect to chemotaxis, cytotoxicity against HCT-116 colon tumor cells, oxidative
      response (chemiluminescence reaction) as well as expression of surface marker
      molecules. We found that Pro alpha 1 was equally effective in stimulating the
      chemotactic activity of PMNs from tumor patients and healthy donors (43%
      increase). PMNs from tumor patients, especially with breast tumor, showed a
      significant enhancement of cytotoxicity against the tumor target cells in
      comparison with healthy donors. With respect to the PMNs cytotoxicity, only about
      50% of the colorectal tumor patients and healthy donors responded to Pro alpha 1
      and FMLP. As to the oxidative response of PMNs, elevated levels were found only
      among colorectal tumor patients. Pro alpha 1 significantly increased the
      oxidative response in breast and colorectal tumor patients by 55% and 25%,
      respectively. Pro alpha 1 decreased the expression of CD16 on PMNs of healthy
      donors, but not that of CD11a, CD11b, CD11c, CD13, CD14, CD15 and CD32.
      Therefore, we suggest, that Pro alpha 1 may improve some PMN functions of tumor
      patients, associated with the proposed role in host-tumor interaction.

PMID- 9568548
TI  - Stimulation of hemopoietic colony formation from mouse marrow cells in vitro
      using human dialyzable leukocyte extracts-IMMODIN-SEVAC.
AB  - The influence of dialyzable extract from human leukocytes (DLE) on the in vitro
      growth of the granulocyte-macrophage colony-forming cell (GM-CFC) colonies from
      progenitors of mouse bone marrow cells was studied. DLE alone did not induce the
      colony growth but it modulated the number of colonies if administered together
      with a colony-stimulating factor (CSF). The costimulatory effect prevailed in a
      broad range of DLE dilution and the index of increase was enhanced with the
      lowering of the CSF concentration. The costimulatory augmentation of clonal
      proliferation of GM-CFC with DLE was further strengthened by addition of
      indomethacin, thus indicating an intervening role of prostaglandins in the
      modulatory influence of DLE.

PMID- 9568547
TI  - The effect of salmeterol on human eosinophils is both stimulus- and response
      dependent.
AB  - Salmeterol, a long-acting beta 2-adrenoceptor agonist, also possesses some anti
      inflammatory properties, but whether eosinophils are the target of such action
      has been equivocal. To clarify the direct effect of salmeterol on eosinophil
      functions, we have studied the effect of the drug on the various responses of
      purified human eosinophils. Superoxide anions (O2-) release and adherence to
      fibronectin-coated plastic plates induced by platelet-activating factor (PAF),
      interleukin-5 (IL-5), leukotriene B4 (LTB4) and phorbol myristate acetate (PMA),
      as well as degranulation induced by C5a and formyl methionyl leucyl phenylalanine
      (FMLP), in the presence of cytochalasin B (CB) were studied. In the concentration
      range 10(-8)-10(-5) M, the drug inhibited PAF- and IL-5-induced O2- release, with
      an IC50 values of 3.2 +/- 1.2 x 10(-7) M and 2.2 +/- 0.4 x 10(-6) M,
      respectively, Superoxide anion release by LTB4 was only modestly inhibited while
      that due to PMA was completely unaffected. On the other hand, eosinophil
      adherence induced by all the 4 stimuli were significantly inhibited within the
      same concentration range. On eosinophil degranulation, the drug failed to
      significantly inhibit the release of eosinophil peroxidase (EPO) induced by
      either C5a or FMLP. In contrast, beta-hexoseaminidase (beta-HA) release by the
      same agents was significantly inhibited, the inhibition being more pronounced for
      FMLP-induced, than C5a-induced release. None of the effects of the drug was
      reversed by the selective beta 2-adrenoceptor antagonist ICI 118551 at a
      concentration of 10(-7) M. These results show that salmeterol may have some
      direct inhibitory effects on human eosinophil functions but that these effects
      are both stimulus- and response-dependent, and are unlikely to be mediated via
      beta 2 adrenoceptors.

PMID- 9568549
TI  - Effect of acute administration of malathion by oral and dermal routes on serum
      histamine levels.
AB  - Previous studies have shown that acute, oral administration of malathion
      increased the generation of a humoral immune response, stimulated macrophage
      function and caused mast cell degranulation and histamine release. In this study,
      the effect of acute administration of various doses of malathion via oral and
      dermal routes to mice and rats on serum levels of histamine was evaluated. Oral
      administration of malathion to mice led to an increase in the level of serum
      histamine 4 and 8 h after administration. At 4 h after administration, the peak
      in serum histamine levels was observed at a dose of 10 mg/kg malathion. At 8 h, a
      maximal effect was observed at a dose of 700 mg/kg and the response was more
      prolonged than at lower doses. At 12 and 24 h after administration, the level of
      histamine in the serum of treated mice was comparable to controls. A similar
      pattern was observed in rats. However, the time point at which histamine levels
      returned to control was 8 rather than 12 h. After application of malathion to the
      skin of mice or rats in dimethyl sulphoxide (DMSO), the level of histamine in the
      blood was also increased. As before, the peak increase was observed at 4 h after
      administration and the level had returned to control levels within 8 h (slight
      increase at 8 h in rats) after application. However, after dermal application the
      maximal levels of histamine in the serum were noted at the highest doses of
      malathion. The no effect levels for histamine in the blood after malathion
      administration to these two species by these two routes are as follows: (1) Mice,
      oral in corn oil, 0.1 mg/kg; (2) Rats, oral in corn oil, 0.1 mg/kg; (3) Mice,
      dermal in DMSO, 2 mg/kg; (4) Rats, dermal in DMSO--not determined (2 mg/kg low
      effect level).

PMID- 9568550
TI  - Modulation of the immune response of Balb/c mice against Leishmania major by
      imuvert.
AB  - This study investigated the effect of Imuvert, a biological response modifier
      derived from Serratia marcescens, on the progression of Leishmania major
      infection in Balb/c mice. A single 100 micrograms Imuvert injection was
      significantly protective in Balb/c mice when challenged 28 days later in the
      footpad with 5 x 10(5) stationary phase L. major promastigotes. Intraperitoneal
      (i.p.) and intravenous (i.v.) immunization of mice with heat-killed stationary
      phase L. major promastigotes significantly reduced lesion development following
      challenge with L. major promastigotes. Subcutaneous (s.c.) immunization had no
      protective effect. A single 100 micrograms Imuvert injection significantly
      reduced lesion development in s.c. immunized mice, but had a lesser effect in
      mice immunized by i.p. and i.v. routes. Balb/c mice receiving four Imuvert
      injections 14, 7, 2 and 1 day prior to footpad challenge with L. major
      promastigotes were not protected, but rather displayed significant exacerbation
      of infection. Our results suggest the possibility that Imuvert could be useful in
      stimulating a protective response against L. major when given along with s.c.
      vaccine, a realistic route for vaccinating humans in contrast to either i.v. or
      i.p. routes. Since the protective response in Balb/c mice against L. major is
      dependent on the stimulation of Th1 cells, it is suggested that the observed
      adjuvant effect of Imuvert given with s.c. vaccine perhaps is due to changes in
      immunological responses in such a direction.

PMID- 9568551
TI  - Differential effects on TNF alpha production by pharmacological agents with
      varying molecular sites of action.
AB  - This study describes the activation conditions for tumor necrosis factor-alpha
      (TNF alpha) production in myelomonocytic U937 cells and human primary peripheral
      blood monocytes in response to lipopolysaccharide (LPS) and/or phorbol 12
      myristate 13-acetate (PMA). PMA itself induced only low levels of TNF alpha
      production with delayed kinetics (e.g. 0.758 +/- 0.128 ng/ml from U937 cells
      after 48 h) while LPS induced greater levels of TNF alpha production in less time
      (e.g. 2.083 +/- 0.96 ng/ml from monocytes in 24 h). Pharmacological agents with
      various molecular sites of action were used to validate the two systems, with the
      protein serine-threonine kinase inhibitors staurosporine and Ro-31-8220, the
      protein tyrosine kinase inhibitor herbimycin A (HBA) and dexamethasone exhibiting
      the greatest potency (IC50S 5-350 nM). In contrast to the effect on TNF alpha
      production, PMA induced strong phosphorylation/activation of p42/p44mapk in
      monocytes by 10 min determined in a mobility shift assay, while LPS was a weaker
      inducer. Additionally, staurosporine (to LPS and PMA) and HBA (to LPS only)
      inhibited the activation of these mitogen-activated protein kinase (MAPK)
      isoforms at doses 10-100 fold higher than those required to inhibit maximal TNF
      alpha production. These data indicate the involvement of the p42/p44mapk
      signalling pathway in LPS-induced pro-inflammatory cytokine production but
      suggest that other signalling pathways are also implicated in this phenomenon.

PMID- 9568552
TI  - Rapid improvement teams.
AB  - BACKGROUND: Suggestions, most of which are supported by empirical studies, are
      provided on how total quality management (TQM) teams can be used to bring about
      faster organizationwide improvements. SUGGESTIONS: Ideas are offered on how to
      identify the right problem, have rapid meetings, plan rapidly, collect data
      rapidly, and make rapid whole-system changes. Suggestions for identifying the
      right problem include (1) postpone benchmarking when problems are obvious, (2)
      define the problem in terms of customer experience so as not to blame employees
      nor embed a solution in the problem statement, (3) communicate with the rest of
      the organization from the start, (4) state the problem from different
      perspectives, and (5) break large problems into smaller units. Suggestions for
      having rapid meetings include (1) choose a nonparticipating facilitator to
      expedite meetings, (2) meet with each team member before the team meeting, (3)
      postpone evaluation of ideas, and (4) rethink conclusions of a meeting before
      acting on them. Suggestions for rapid planning include reducing time spent on
      flowcharting by focusing on the future, not the present. Suggestions for rapid
      data collection include (1) sample patients for surveys, (2) rely on numerical
      estimates by process owners, and (3) plan for rapid data collection. Suggestions
      for rapid organizationwide implementation include (1) change membership on cross
      functional teams, (2) get outside perspectives, (3) use unfolding storyboards,
      and (4) go beyond self-interest to motivate lasting change in the organization.
      CONCLUSIONS: Additional empirical investigations of time saved as a consequence
      of the strategies provided are needed. If organizations solve their problems
      rapidly, fewer unresolved problems may remain.

PMID- 9568553
TI  - A randomized controlled trial of CQI teams and academic detailing: can they alter
      compliance with guidelines?
AB  - BACKGROUND: The availability of clinical guidelines in isolation has generally
      failed to promote voluntary change in practice patterns. Accordingly, a
      randomized controlled trial was conducted to determine the effectiveness of
      academic detailing (AD) techniques and continuous quality improvement (CQI) teams
      in increasing compliance with national guidelines for the primary care of
      hypertension and depression. METHODS: Fifteen small group practices at four
      Seattle primary care clinics were assigned to one of three study arms--AD alone,
      AD plus CQI teams, or usual care. The activity of 95 providers and 4,995 patients
      was monitored from August 1, 1993, through January 31, 1996. Twelve-month
      baseline and study periods were separated by a six-month "wash-in" period during
      which training sessions were held. Changes in hypertension prescribing, blood
      pressure control, depression recognition, use of older tricyclics, and scores on
      the Hopkins Symptom Checklist depression scale were examined. RESULTS: Clinics
      varied considerably in their implementation of both the AD and the CQI team
      interventions. Across all sites, AD was associated with change in a single
      process measure, a decline in the percentage of depressives prescribed first
      generation tricyclics (-4.7 percentage points versus control, p = 0.04). No
      intervention effects were demonstrated for CQI teams across all sites for either
      disease condition. Within the clinic independently judged most successful at
      implementing both change strategies, the use of CQI teams and AD in combination
      did increase the percentage of hypertensives adequately controlled (17.3
      percentage points versus control, p = 0.03). SUMMARY AND CONCLUSIONS: The AD
      techniques and the CQI teams evaluated were generally ineffective in improving
      guideline compliance and clinical outcomes regarding the primary care of
      hypertension and depression.

PMID- 9568554
TI  - Clinical process improvement as a means of facilitating health care system
      integration.
AB  - BACKGROUND: In recent years many health care providers, physicians, hospitals,
      and managed care organizations have undergone significant reorganization in both
      delivery and financing systems. This has created new organizations called
      integrated or organized delivery systems. Sentara Health System (Norfolk, Va),
      one of these new integrated entities, developed a unified strategy for clinical
      process improvement for the entire organization. This system-wide approach had
      unanticipated problems and benefits. METHODS: The Sentara Health System created a
      team responsible for coordinating clinical process improvement activities across
      its hospitals and ambulatory physician sites. A steering committee directed this
      team to improve the organization and delivery of care for specific high-cost,
      high-volume, or problem-prone disease for physicians to manage. A standardized
      approach aimed at coordinating care across sites was the cornerstone of these
      activities. RESULTS: Significant improvements in patient outcomes and a
      concomitant decrease in costs of care were accomplished for multiple diseases and
      procedures. These projects uncovered unanticipated barriers to implementing
      improvement projects in a complex health care system which make implementing
      these activities far more difficult than for an individual hospital with its
      medical staff. CONCLUSION: Coordinating clinical improvement activities across
      multiple hospitals and other sites of care in a complex integrated delivery
      system serves important purposes in addition to improving patient care. These
      projects were an important cultural change agent to transform the individual
      components of the system into one that is capable of delivering care continuously
      across multiple sites. Standardization of care practices, policies, and
      procedures is considerably enhanced by coordinating these activities across the
      entire system.

PMID- 9568555
TI  - Reframing beliefs about work and change processes in redesigning laboratory
      services.
AB  - BACKGROUND: In 1996 a team started meeting to redesign care at Intermountain
      Health Care's (Salt Lake City) laboratory services on a fast track to dovetail
      with remodeling of the physical layout. The team reframed its current beliefs
      about using team processes--including use of a consultant/facilitator, team size,
      and decision making (by criteria instead of consensus). MEASUREMENT: Although the
      lab was strong in technical measurements, the sole management measurement before
      redesign was financial data generated by the accounting department. A
      comprehensive measurement system, which was required for the lab to evaluate the
      impact of the redesign efforts and manage its operations over time, constituted
      the team's first steps toward implementing the redesign effort. PROCESS REDESIGN:
      Once the team understood the purpose, customer expectations, desired outcomes of
      the specimen flow process, and the reasons for current breakdowns, it was able to
      design an ideal high-level process (with a floor plan to support it). Multiple
      subprocesses were redesigned and implemented on the basis of reframed beliefs-
      for example, that the process starts and ends with the customer (clinician or
      patient) and that there is one standardized entry point into the lab to reduce
      variability in processing and assign priority for analysis of specimens. For
      example, the team identified opportunities for improvements in the manner in
      which laboratory test results were communicated to physicians' offices. SUMMARY:
      The belief that appeared to have the most profound impact on the redesign effort
      was the clarification of the fundamental purpose of laboratory services and how
      it shapes every aspect of the business.

PMID- 9568556
TI  - Species-specificity of growth-promoting effects of prolactin during rat
      embryogenesis.
AB  - In the early stages of embryonic development, many growth-promoting molecules
      must be provided by the maternal system. The molecules involved in growth
      processes may be either hormones or growth factors, or molecules that interact
      with such factors. The pregnancy related hormone, prolactin (PRL, MW 23 kDa) has
      been implicated in the control of embryonic growth. The growth-promoting
      potential of PRL and its species-specificity was investigated by culturing 9.5 d
      rat embryos in vitro for 48 h in depleted serum in the presence and absence of
      PRL from 3 different species. The growth-supporting capacity of the serum was
      reduced by removal of low molecular weight molecules by prolonged filtration of
      the serum using filters with a molecular weight exclusion of 30 kDa. This method
      provided a 'semidefined' medium (retenate) in which embryonic growth and
      development was significantly reduced, demonstrating that the low molecular
      weight fraction of serum may contain some growth-promoting factors. Addition of
      PRL (0.4-25.6 ng/ml) from different species (human, sheep and rat) to retenate
      significantly improved embryonic growth and development, suggesting that the
      developing embryo may utilise PRL. Amongst PRLs, rat PRL was found to be active
      at much lower concentrations than either of the other molecules, and human PRL
      had more effect in low concentrations than sheep PRL suggesting a species
      specificity for this hormone. It may be that the PRL receptors of the rat embryos
      have greater affinity for the rat hormone as different responses for hormones
      from different species have been shown. These findings suggest that embryos may
      be able to utilise maternally derived PRL during organogenesis.

PMID- 9568558
TI  - Intrastriatal grafts of rat colonic smooth muscle lacking myenteric ganglia
      stimulate axonal sprouting and regeneration.
AB  - Grafts of living or freeze-killed freshly dissected colonic smooth muscle from
      young inbred Fischer rats were implanted into the corpus striatum of adult
      Fischer rats. Sections of brain were examined electron microscopically 3 and 6 wk
      after implantation. At both times, living grafts were vascularised and contained
      healthy differentiated smooth muscle cells, fibroblasts, interstitial cells of
      Cajal and some macrophages. Large bundles of small nonmyelinated axons,
      identified as CNS axonal sprouts, could be observed in the brain at and near the
      interface between the living smooth muscle and the CNS tissue. Bundles of
      regenerating CNS axons, often associated with astrocyte processes, had grown into
      the grafts. Some axons within the grafts had matured, enlarged and become
      myelinated by oligodendrocyte processes or Schwann cells. In some cases, smooth
      muscle cells were observed in close and intricate association with axons. In
      contrast to the living grafts, grafts of freeze-killed smooth muscle, examined 3
      and 6 wk after implantation, contained macrophages, fibroblasts, collagen and
      large amounts of cellular debris, but no living muscle cells, astrocytes or
      Schwann cells. The striatal neuropil around freeze-killed grafts did not contain
      large bundles of CNS axonal sprouts and bundles of axons were not observed within
      the freeze-killed graft. This study demonstrates that cells from the smooth
      muscle layers of the colon, in the absence of myenteric ganglia, can stimulate a
      vigorous regenerative response from CNS axons when implanted into the corpus
      striatum of adult rats.

PMID- 9568557
TI  - Ultrastructural and cytochemical evaluation of sepsis-induced changes in the rat
      pulmonary intravascular mononuclear phagocytes.
AB  - Sepsis stimulates an increase in the number and activity of mononuclear
      phagocytes in systemic host-defence organs. The present study was conducted to
      define the ultrastructural and cytochemical characteristics of the mononuclear
      phagocytes that sequester in the lung microvasculature of septic rats. Fourteen
      rats were challenged with a single intraperitoneal injection of saline (0.5
      ml/100 g), E. coli (2 x 10(7)/100 g) or glucan (4 mg/100 g), and euthanased 2, 4,
      or 7 d later. The lungs were inflation fixed and processed for transmission
      electron microscopy. Cellular morphology was used to identify the intravascular
      mononuclear phagocytes and acid phosphatase (AcPase) expression was monitored as
      an index of cellular differentiation and activation. Control rats contained a
      limited number of monocytes in the pulmonary vasculature. In contrast, large
      numbers of activated mononuclear phagocytes were seen in the microvasculature
      within 48 h of treatment with either microbial product. The recruited pulmonary
      intravascular mononuclear phagocytes (PIMP) exhibited AcPase-reactive Golgi
      complexes, accumulation of secretory vesicles and other features of cell
      activation consistent with enhanced biosynthetic activity. Subsequent electron
      microscopy, conducted 4 and 7 d posttreatment, suggested that a progressive
      decline in the number and activity of PIMPs then occurred. In order to quantify
      the sepsis-induced accumulation of AcPase-positive PIMP, the experimental
      challenges were repeated in 11 rats and, 48 h later, tissue samples were
      evaluated by light microscopy for tartrate-insensitive acid phosphatase. Control
      rats exhibited 0.148 +/- 0.107 AcPase-positive PIMP/alveoli. E. coli and glucan
      challenged animals exhibited significant (P < 0.01) increases in AcPase-positive
      mononuclear phagocytes, with 0.782 +/- 0.073 and 0.636 +/- 0.170 PIMP/alveoli
      respectively. The results demonstrate that focal sepsis stimulates a significant,
      but transient, recruitment of activated mononuclear phagocytes into the rat
      pulmonary microvasculature.

PMID- 9568559
TI  - Vascular tissue adaptations in end-to-end autologous arterial grafts in rats: a
      morphometric analysis.
AB  - Autologous vein grafts are employed extensively to bypass stenoses in the
      arterial circulation. More recently arterial segments have been used for such
      bypass surgery. In this study the adaptation of regenerating vascular tissues in
      experimental autologous artery grafts (4 mm long and 1 mm in diameter) in 20
      adult male Wistar rats was analysed. At 1, 2, 4, 8 and 16 wk after insertion, 4
      grafts per time interval were removed, processed for high resolution light
      microscopy and the thicknesses of the media and neointima, as well as the area
      fractions of smooth muscle cells, were analysed morphometrically. All grafts were
      reendothelialised by 2 wk. Neointimal hyperplasia (a subendothelial layer of
      smooth muscle cells) developed in all grafts and reached its maximal thickness
      (40.4 +/- 4.7 microns) at 2 wk. The area fraction of smooth muscle cells in the
      neointima of the artery grafts did not change significantly at any time from 2 to
      16 wk. The media underlying the neointima of the artery grafts remained
      relatively constant throughout the 16 wk duration of the experiment. Whilst the
      total wall thickness of the grafts reduced significantly between 2 and 4 wk after
      insertion, at all times the grafts were thicker than the host artery.

PMID- 9568560
TI  - Specialised sympathetic neuroeffector associations in rat iris arterioles.
AB  - Vascular sympathetic neuroeffector associations have been examined in rat iris
      arterioles using serial section electron microscopy and reconstruction
      techniques. Examination of random sections showed that, of all profiles of
      varicosities (199) seen to lie closer than 4 microns to vascular smooth muscle
      cells, only a small proportion (29/199) were found in close association with
      vascular smooth muscle cells, where adjacent membranes were separated by less
      than 100 nm. However, serial section examination, from intervaricose region to
      intervaricose region, of 79 varicosities similarly observed lying within 4
      microns of vascular smooth muscle cells showed that 54 formed close associations
      with vascular smooth muscle cells. In serial sections, all these varicosities
      were also closely associated with melanocytes and of the 25 remaining
      varicosities, 22 formed close associations with melanocytes alone, whilst 3 did
      not come into close association with any effector cell. The increased observation
      of close associations with vascular smooth muscle cells in serial sections,
      compared with random sections, is consistent with the demonstration that the area
      of contact only occupies, on average, a small percentage (5%) of the total
      surface area of the varicosity as seen in the 3-dimensional reconstructions. In
      both random and serial sections, close associations were observed between
      varicosities and vascular smooth muscle cells or melanocytes irrespective of
      whether fibres were present singly or in small nerve bundles. Three-dimensional
      reconstruction of associations of varicosities and vascular smooth muscle cells
      demonstrated several common features, such as accumulations of synaptic vesicles
      and loss of Schwann cell covering at the region of membrane facing the effector
      cell. The similarity in the appearance of the neuroeffector association seen in
      this study and those described in previous studies provides evidence for the
      existence of a common sympathetic neuroeffector association, irrespective of the
      receptor subtype involved in neurotransmission.

PMID- 9568561
TI  - Analysis of interdigital spaces during mouse limb development at intervals
      following amniotic sac puncture.
AB  - A spectrum of limb abnormalities ranging from adactyly, syndactyly,
      acrosyndactyly to nail hypoplasia was encountered in mouse embryos subjected to
      amniotic sac puncture at the corresponding gestational stage when human chorionic
      villus sampling (cvs) would normally be performed clinically. Previous skeletal
      studies revealed that, apart from the occasional incidence of fusion of 2 distal
      phalanges, syndactyly usually only affected the soft tissues within the
      interdigital spaces. A similar situation was also observed in cases of adactyly;
      while the skeletal elements of the digits were present, the soft tissues in the
      interdigital spaces failed to separate. A transient period of bradycardia is
      induced, possibly secondary to compression of the embryo by the extraembryonic
      membranes and uterine muscles following amniotic sac puncture. These factors, we
      believe, produce temporary hypoxia/ischaemia of the distal extremities, and may
      lead to the modification of the interdigital mesenchymal tissues within the
      autopods. In order to investigate the mechanism(s) underlying soft tissue
      syndactyly, limbs recovered at 0.5, 4, 8, 12, 24, or 36 h following amniotic sac
      puncture (ASP) were examined histologically. Vascular disruption in the form of
      localised areas of haemorrhage, vascular dilatation and congestion and the
      presence of fluid-filled cavities occurred in relation to the marginal vein and
      vascular plexus in the interdigital spaces. It is hypothesised that this
      interfered with the normal equilibrium of the preset programs of mitosis/cell
      death and apoptosis within the mesenchymal cells of the interdigital spaces.
      Apoptosis in these areas was inhibited in the majority of the experimental limbs
      analysed 4 h after ASP. Instead of undergoing necrosis/apoptosis, increased
      mitotic activity was usually observed from 8 h following ASP at the sites where
      apoptosis would normally be expected to be seen. The aberrant fate of the
      interdigital mesenchyme following ASP and the underlying mechanism(s) involved
      are discussed, as is the critical importance of an adequate vascular supply to
      the interdigital spaces during the morphogenesis of the autopod. We believe that
      this report contributes to understanding the mechanism(s) which lead to
      syndactyly following ASP, and the limb defects occasionally seen following cvs
      when this is undertaken during early gestation.

PMID- 9568562
TI  - Postmortem changes in the immunohistochemical demonstration of nerves in human
      ventricular myocardium.
AB  - In order to delineate the effects of death on the immunofluorescence of autonomic
      nerves supplying the human ventricular myocardium, we studied percutaneous
      myocardial samples obtained postmortem from 5 individuals within 3 h of death.
      Subsequent samples were obtained daily from the same individuals up to a total of
      5-11 d. The antibodies employed included those against protein gene product 9.5
      to demonstrate nervous tissue, dopamine beta-hydroxylase and tyrosine hydroxylase
      to reveal catecholaminergic neural tissue and neuropeptide Y. An indirect
      immunofluorescence technique using the avidin-biotin method was employed. The
      density of myocardial protein gene product 9.5 immunoreactive nerves declined on
      the 7th day, and became markedly diminished by the 11th day. Immunoreactive
      dopamine beta-hydroxylase nerves decreased on the 5th day, and were difficult to
      identify by the 9th day. The density of tyrosine hydroxylase and neuropeptide Y
      containing nerves rapidly diminished on the 3rd and 4th days, and became
      undetectable by the 7th and 8th days, respectively. The present results indicate
      that, depending on the type of antibodies used, immunohistochemical techniques
      can be used on human hearts obtained up to within 6 d of death to study cardiac
      innervation.

PMID- 9568564
TI  - Target pioneering and early morphology of the murine chorda tympani.
AB  - Many studies demonstrate that differentiation of certain sensory receptors during
      development is induced by their nerve supply. Thus the navigational accuracy of
      pioneering fibres to their targets is crucial to this process. The special
      gustatory elements of the facial and glossopharyngeal nerves are used extensively
      as model systems in this field. We examined the chorda tympani, the gustatory
      component of the facial nerve, to determine the precise time course of its
      development in mice. The transganglionic fluorescent tracer DiI was injected into
      the anterior aspect of the mandibular arch of fixed embryos aged between 30 and
      50 somites (E10-E12). It was allowed to diffuse retrogradely via the geniculate
      ganglion to the brainstem for 4 wk, before the distribution of DiI was determined
      using confocal laser scanning microscopy. Geniculate ganglion cells were first
      labelled at the 34 somite stage (E10). Pioneering chorda tympani fibres that
      arise from these cells passed peripherally and followed an oblique course as they
      grew towards the mandibular arch. At the 36 somite stage (E10.5), the peripheral
      component followed an intricate postspiracular course and passed anteriorly to
      arch over the primitive tympanic cavity, en route to the lingual epithelium. From
      the 36 to 50 somite stages (E10.5-E12), it consistently traced in the fashion of
      a 'U' bend. The central fascicle also traced at the 36 somite stage (E10.5) and
      just made contact with the brainstem. At the 40 somite stage (E11), the central
      fibres clearly chose a route of descent into the spinal trigeminal tract and
      branched into the solitary tract. Pioneering chorda tympani fibres contact the
      lingual epithelium when the target is primordial. The lingual epithelium may be a
      source of a neurotropic factor that attracts peripheral chorda tympani fibres to
      the sites of putative papillae. However, the chorda tympani is probably not a
      vital influence on the subsequent differentiation of gustatory papillae, since
      the papillae are elaborated 5 d later at E15 in murine embryos. The early
      morphology of the nerve is true to the amniote vertebrate phenotype.

PMID- 9568563
TI  - Thickness of the subchondral mineralised tissue zone (SMZ) in normal male and
      female and pathological human patellae.
AB  - The objective of this paper was to analyse sex differences of the thickness of
      the subchondral mineralised tissue zone (SMZ), and to find out whether systematic
      changes of SMZ thickness are associated with naturally occurring, non-full
      thickness cartilage lesions of human patellae. In 32 methyl-methacrylate-embedded
      specimens (16 normal, 8 with focal medial, and 8 with lateral lesions) the SMZ
      thickness was determined, using a binocular macroscope and an image analysing
      system. In each case, the thickness distribution was reconstructed throughout the
      entire joint surface. The maximal and mean SMZ thicknesses were significantly
      higher in males than in females (P < 0.01). In normal patellae and those with
      lateral lesions, the thickness was significantly thicker laterally than medially
      (P < 0.05), but it was not in specimens with medial damage. Patellae with medial
      damage exhibited a significantly lower total mean and lateral mean (P < 0.05). A
      lower SMZ thickness was found directly beneath medial lesions than beneath
      lateral ones, but the local thickness was always in the range of that observed in
      normal specimens. We conclude that differences of patellar SMZ thickness exist
      between males and females. Naturally occurring cartilage lesions appear, however,
      not to be associated with local changes of SMZ thickness, but they may be
      associated with an altered regional distribution pattern within the joint
      surface.

PMID- 9568565
TI  - Quantification of the collagen fibre architecture of human cranial dura mater.
AB  - The purpose of this study was to quantify and map the gross fibre architecture of
      the cranial dura mater (CDM) using small angle light scattering (SALS). In SALS,
      HeNe laser light is passed through the tissue, and the resultant scattering
      pattern is analysed to determine the preferred fibre direction and degree of
      orientation. The dura mater was found to be a complex structure with fibre
      orientations ranging from highly aligned to nearly random. In the temporal
      region, 80% of the samples (n = 20) were found to have regions composed of highly
      oriented fibres with a mean fibre direction of 6.3 degrees +/- 0.8 degree with
      respect to the sagittal plane (i.e. almost parallel to the superior sagittal
      sinus). These highly aligned regions were found in symmetric anatomical locations
      about the median sagittal sinus and had similar fibre orientations over both
      hemispheres. Although our sample size was small, we found that the size of the
      symmetric regions, which covered 14.4 +/- 1.6% of the total CDM area, was not
      influenced by subject's age or sex. The presence of these highly oriented fibre
      regions in CDM may be due to mechanical forces exerted on dura mater during its
      development. These forces may have induced realignment of the collagen fibres in
      the direction of tensile pull, although the exact basis for the unique gross
      fibre architecture of CDM remains unknown.

PMID- 9568568
TI  - An unusual structure of venules in tonsils of the soft palate of young pigs.
AB  - In tonsils of the soft palate of pigs high endothelial venules (HEV) occur
      throughout the parafollicular region. In some regions of the venules the
      endothelial lining is uniformly high; in other areas, mainly the nuclear region
      of the endothelial cell protrudes into the lumen and the cytoplasmic region is
      attenuated. In this portion of the venule endothelial cells may traverse the
      lumen of the vessel to form intravascular bridging processes. The endothelial
      cells are characterised by pinocytotic vesicles, many surface microvilli,
      cytoplasmic processes and local cell-cell contacts with adjacent endothelial
      cells. These specialised HEV may play a role in the unusual pattern of
      lymphocytes from tonsillar tissue into blood. In the tonsils of the soft palate
      of pigs, HEV may mediate both lymphocyte migration to and from the lymphoid
      tissue. Further investigation is required to determine the importance of these 2
      migration pathways.

PMID- 9568569
TI  - Brain damage may be reversible in patients with Alzheimer's.

PMID- 9568567
TI  - Nucleation and capture of large cell surface-associated microtubule arrays that
      are not located near centrosomes in certain cochlear epithelial cells.
AB  - This report deals with the as yet undetermined issue of whether cell-surface
      associated microtubules in certain cochlear epithelial cells are centrosomally
      nucleated and subsequently migrate to microtubule-capturing sites located at the
      surface regions in question. Alternatively, the cells may possess additional
      nucleating sites which are noncentrosomal and surface-associated. These
      alternative possibilities have been investigated for highly polarised epithelial
      cells called supporting cells in the mouse and guinea pig organ of Corti using
      antibodies to pericentrin and gamma-tubulin. There is substantial evidence that
      both proteins are essential components of microtubule-nucleating sites in cells
      generally. Each mature supporting cell possesses a large microtubule array that
      is remotely located with respect to its centrosome (more than 10 microns away).
      The antibodies bind to a cell's centrosome. No binding has been detected at 2
      other microtubule-organising centres that are associated with the ends of the
      centrosomally-remote microtubule array while it is being constructed. Such arrays
      include thousands of microtubules in some of the cell types that have been
      examined. If all a cell's microtubules are nucleated by its centrosome then the
      findings reported above imply that microtubules escape from the centrosomal
      nucleating site and migrate to a new location. Furthermore capture of the plus
      and minus ends of the errant microtubules is taking place because both ends of a
      centrosomally-remote microtubule array are attached to sites that are precisely
      positioned at certain cell surface locations. Minus ends are locating targets
      with an exactitude comparable to that which has been demonstrated for plus ends
      in certain cell types. These cells apparently operate a single control centre
      strategy for microtubule nucleation that is complemented by precise positioning
      of plus and minus end-capturing sites at the cell surface.

PMID- 9568570
TI  - In sickness and in health: an exploration of the perceived quality of the marital
      relationship, coping, and depression in caregivers of spouses with Alzheimer's
      disease.
AB  - Caring for a spouse with Alzheimer's disease (AD) is a complex task influenced by
      numerous factors including the quality of the past and present marital
      relationship. Assessment of both the caregiver's perception of the quality of the
      past marital relationship and how he or she traditionally coped with marital
      discord is important for planning effective interventions. AD support groups that
      work with both the caregiver and the afflicted spouse on problem-solving skills
      may strengthen or help preserve the marital relationship.

PMID- 9568566
TI  - Innervation of intestinal arteries by axons with immunoreactivity for the
      vesicular acetylcholine transporter (VAChT).
AB  - The presence of a cholinergic innervation of arterioles within the gut wall is
      suggested by pharmacological studies of nerve mediated vasodilatation, but
      attempts to identify nerve cells that give rise to cholinergic vasodilator fibres
      have yielded discrepant results. In the present work, antibodies to the vesicular
      acetylcholine transporter protein (VAChT) were used to investigate the
      relationships of immunoreactive nerve fibres to submucosal arterioles. Comparison
      was made with cerebral arteries, which are known to be cholinergically
      innervated. Double labelling immunohistochemical techniques revealed separate
      VAChT and tyrosine hydroxylase (TH) immunoreactive (IR) fibres innervating all
      sizes of arteries of the submucosa of the stomach, ileum, proximal colon, distal
      colon and rectum as well as the cerebral arteries. Arterioles of all digestive
      tract regions had greater densities of TH-IR innervation than VAChT-IR
      innervation. In the ileum, double labelling for VAChT-IR and VIP-IR or calretinin
      IR showed more VAChT-IR than either VIP-IR or calretinin-IR fibres. Calretinin-IR
      and VAChT-IR were colocalised in a majority of calretinin-IR axons, but VIP-IR
      and VAChT-IR were not colocalised. All calretinin-IR nerve cells in submucous
      ganglia were immunoreactive for choline acetyltransferase, but only 1-2% of VIP
      IR nerve cells were immunoreactive. Extrinsic denervation of the ileum did not
      alter the distribution of VAChT-IR fibres, but it eliminated TH-IR fibres.
      Removal of myenteric ganglia (myectomy) did not alter the distribution of fibres
      with VAChT or TH-IR. This work thus provides evidence for cholinergic innervation
      of intrinsic arterioles throughout the digestive tract and indicates that the
      fibres in the small intestine originate from submucosal nerve cells.

PMID- 9568571
TI  - Discharges against medical advice. Provider accountability and psychiatric
      patients' rights.
AB  - If clinicians decide to prevent a voluntary patient from leaving a facility,
      proper protocols must be followed within the time limits defined in that state's
      laws on detentions. AMA discharges can sometimes be prevented by expedient
      treatment that includes involving the patient in goal-setting, adequate patient
      teaching, and appropriate discharge planning. Hospital management personnel
      should be familiar with individual state laws on detention protocols and should
      assist staff in resolving irregular discharge questions.

PMID- 9568572
TI  - Increasing resiliency to substance abuse in recovering women with comorbid
      depression.
AB  - Nurses must recognize that substance abusing women with a comorbid depression are
      likely to view the present, past, and future negatively, hold distorted views of
      the world, hold irrational false beliefs, and have a low self-esteem. Assisting
      women to recognize and own their feelings and accept responsibility for
      controlling them are crucial to changing their thoughts, feelings, and behaviors
      that contribute to low self-esteem and depression. Affirmations can be used to
      increase one's self-esteem through changing one's view of self and the world, and
      behavioral strategies can be used to change behavior and subsequently one's
      feelings.

PMID- 9568573
TI  - Formal and informal care of people with psychiatric disorders: historical
      perspectives and current trends.
AB  - People with severe and persistent mental illness have a broad array of needs
      related to health and well being. In the present era of shrinking health care
      resources and managed care, it is not likely that the formal health care system
      can or will be sufficiently responsive to the needs of this population. To
      address adequately the care and treatment of individuals with serious mental
      illness, it is essential to identify and use all available resources, both in the
      formal health care system and within informal systems of care.

PMID- 9568574
TI  - Preference vs. necessity.

PMID- 9568575
TI  - Perceived needs of parents of critically ill children.
AB  - PURPOSE: To identify the needs of parents of critically ill hospitalized children
      as perceived by the parents and critical care nurses, and to identify any
      differences between the two groups. DESIGN: Descriptive, comparative. SETTING:
      Pediatric intensive care unit (PICU) in a Midwestern hospital. PARTICIPANTS: A
      nonprobability convenience sample of parents or primary caregivers of critically
      ill children (n = 21) and pediatric critical care nurses (n = 17). OUTCOME
      MEASURES: Critical Care Family Needs Inventory modified for pediatrics and
      demographic questionnaires. RESULTS: Information, assurance, and proximity to the
      critically ill child were identified as priority needs of the PCGs in this study.
      Significant differences on specific needs were identified between PCG/nurse
      matched pairs; however, no significant differences were found in total scores
      between the two groups by a two-tailed paired t test. CONCLUSIONS: This study
      supports the need to investigate interventions to better address parental needs
      of critically ill children. By consistent identification, prioritization, and
      incorporation of parental needs into the plan of care, nurses can assist the
      parents in the recognition and fulfillment of needs that have less perceived
      importance. Research-based interventions will facilitate improved parental
      adaptation to their child's critical hospitalization.

PMID- 9568576
TI  - Varicella zoster infection in the immunocompromised child.
AB  - PURPOSE: To describe varicella zoster virus infection in the immunocompromised
      child and provide guidelines to decrease the risk of infection and complications
      for these children. POPULATION: Children infected with varicella zoster virus,
      particularly those with a compromised immune system. CONCLUSIONS: Varicella
      zoster virus infection can have serious consequences for children with
      malignancies and infection with the human immunodeficiency virus, as well as
      children on chronic steroid therapy. PRACTICE IMPLICATIONS: The advanced practice
      nurse often is responsible for identifying those children at increased risk for
      VZV infection and its complications and for planning and implementing
      interventions to decrease the risks to the immunocompromised child.

PMID- 9568577
TI  - Prescriptive theory of acute pain management in infants and children.
AB  - PURPOSE: To present a middle-range nursing theory of acute pain management that
      provides direction for practice and research. CLIENT POPULATION: Patients from 6
      months to 12 years old who have acute pain. CONCLUSIONS: The potential of the
      proposed theory, Acute Pain Management in Infants and Children, is to assist
      nurses in managing clinical pain and to expand the knowledge and research base in
      children's pain. PRACTICE IMPLICATIONS: To provide clinicians with prescriptions
      for pain reduction and a conceptual basis for pain interventions. Statement and
      theory testing are needed to determine adequacy of this theory for infants and
      children experiencing acute pain.

PMID- 9568579
TI  - Children with asthma.

PMID- 9568578
TI  - Welfare reform: loss of supplemental security income (SSI) for children with
      disabilities.
AB  - PURPOSE: To describe the changes the new welfare reform legislation, the Personal
      Responsibility and Work Opportunity Reconciliation Act of 1996, makes in
      children's eligibility for Supplemental Security Income (SSI) and the
      implications of the changes for low-income children with disabilities and their
      families. POPULATION: Low-income children and youth, 18 years of age and younger,
      who have one or more limitations in physical or mental function in performing age
      appropriate skills. CONCLUSIONS: The tightened federal standards for determining
      whether children are disabled place thousands of children at risk for losing SSI
      cash benefits. This loss of necessary financial support has the potential to
      adversely affect the physical and psychological health of low-income children
      with disabilities and their families. The new law represents a step backward from
      the long awaited gains the 1990 Zebley v. Sullivan U. S. Supreme Court decision
      legislated for children with disabilities. PRACTICE IMPLICATIONS: Knowledge of
      the legal changes in children's SSI enables nurses to implement interventions
      that help low-income families maintain SSI eligibility for their children with
      disabilities and to advocate with the public and policymakers on behalf of this
      vulnerable population.

PMID- 9568580
TI  - Getting nursing research going in a community hospital with limited resources.
AB  - In today's rapidly changing healthcare environment, validating nursing practice
      is more important than ever. Research findings can be used to improve the quality
      of care, demonstrate cost-effectiveness, and confirm the need for professional
      nursing practice. Even with limited resources, research activities can become an
      integral part of your nursing practice. Assess your current assets, then start
      with a feasible project you feel strongly committed to. Work to develop your
      skills, support, and resources as you create a research-friendly environment. The
      greatest reward will be knowing you are providing the best nursing care possible.

PMID- 9568581
TI  - Spontaneous mutation in lacI transgenic mice: a comparison of tissues.
AB  - The nature of spontaneous mutations in the lacI transgene of Big Blue mice was
      determined in selected tissues. The mutant frequencies ranged from 2.5 x 10(-5)
      to 7.1 x 10(-5) for liver, spleen, bladder, stomach, kidney, bone marrow, lung
      and skin. We also determined the DNA sequence alterations in the mutants
      recovered from these tissues. In all tissues the predominant class of mutations
      was G:C-->A:T transitions, most of which occurred at 5'-CpG-3' dinucleotide
      sequences. Bladder, kidney and skin display the highest contribution of G:C-->A:T
      transitions. The second most common class of mutations was G:C-->T:A
      transversions. All other base substitution classes contributed < 10% each. Of the
      non-substitution events, the loss of a single base pair was the most frequently
      occurring event (< 10%). The similarity of mutational spectra (in terms of kinds
      of mutations detected by the lacI transgenic system) in all tissues examined
      supports the idea that similar mutational pathways function in these tissues in
      the absence of chemical or physical stimulus.

PMID- 9568582
TI  - In vitro mutagenicity and genotoxicity study of a number of short-chain
      chlorinated hydrocarbons using the micronucleus test and the alkaline single cell
      gel electrophoresis technique (Comet assay) in human lymphocytes: a structure
      activity relationship (QSAR) analysis of the genotoxic and cytotoxic potential.
AB  - Using the micronucleus (MN) test and the alkaline single cell gel electrophoresis
      (Comet) assay, potential mutagenicity (MN formation), genotoxicity (DNA breakage
      capacity) and cytotoxicity (cell proliferation reduction) of five chlorinated
      hydrocarbons (carbon tetrachloride, hexachloroethane, 1,2-dichloroethane, 1
      chlorohexane and 2,3-dichlorobutane) have been evaluated in isolated human
      lymphocytes. With the MN test a low but statistically significant mutagenic
      activity was detected for all tested substances (except 2,3-dichlorobutane) with
      one out of the two donors and in the presence or absence of an exogenous
      metabolic activation system (S9 mix). However, at the concentration ranges tested
      none of the positive compounds induced a clear dose-dependent mutagenic effect.
      The Comet assay detected a strong DNA damaging effect for 1-chlorohexane, 2,3
      dichlorobutane and 1,2-dichloroethane, but not for carbon tetrachloride and
      hexachloroethane. The influence of metabolism on the genotoxic activity of the
      chemicals was more clear in the Comet assay than in the MN test. The experimental
      genotoxicity and cytotoxicity data obtained in this study, together with data on
      five more related chemicals previously investigated, and their physico-chemical
      descriptors or electronic parameters have been used for QSAR analysis. The QSAR
      analysis high-lighted that the toxicity of the tested compounds was influenced by
      different parameters, like lipophilicity (logP), electron donor ability (charge)
      and longest carbon-chlorine (LBC-Cl) bond length. In addition, steric parameters,
      like molar refractivity (MR) and LBC-Cl, and electronic parameters, like ELUMO
      (energy of the lowest unoccupied molecular orbital, indicating electrophilicity),
      were predominant factors discriminating genotoxins from non-genotoxins in the
      presence but not in the absence of S9 mix. Although a limited number of compounds
      have been examined and cytotoxicity and genotoxicity were identified in two
      different bioassay tests, the data set was obtained by the same experimentor,
      strengthening the reliability of the QSAR.

PMID- 9568584
TI  - Mutagenicity of ethyl carbamate to lacZ- transgenic mice.
AB  - The mutagenicity of the rodent carcinogen ethyl carbamate (EC, urethane) has been
      assessed using the lacZ- transgenic mouse mutation assay (Muta Mouse). In two
      separate experiments a single i.p. dose of 900 mg/kg urethane followed by a 14-16
      day expression period yielded statistically significant (approximately 2-fold)
      increases in mutation frequency (MF) in the lung and liver of the mice. In the
      second experiment MF in the spleen and bone marrow was also assessed and
      statistically significant increases in MF were observed in each case.
      Concomitantly conducted bone marrow micronucleus assays gave 15.8- and 8-fold
      increases respectively in the incidence of micronucleated polychromatic
      erythrocytes in the two studies.

PMID- 9568583
TI  - Mutation frequency decline in MMS-treated Escherichia coli K-12 mutS strains.
AB  - It has been shown that the decline in mutant frequency (MFD) (argE3(ochre)-
      >Arg+) which occurs in MMS-treated and then transiently starved AB1157
      Escherichia coli K-12 cells concerns revertants which arose by supL suppressor
      formation in a process which is umuDC dependent. Here we have examined whether
      MMS-induced Arg+ revertants are susceptible to decline when bacteria are
      deficient in mismatch repair. We show that there is an absence of MFD in MMS
      treated M1 (mutS) and in EC2416 (mutS delta umuDC) cells defective in mismatch
      repair which is associated with a change in the spectrum of MMS-induced mutations
      formed. In contrast to AB1157, transformation of M1 (mutS) bacteria with plasmids
      harbouring various combinations of umuD(D')C genes does not enhance the level of
      MMS-induced mutations but may influence the proportion of supL mutations. These
      supL mutations show MFD. Repair processes under MFD conditions were confirmed by
      analysis of plasmid DNA isolated from MMS-treated bacteria at different stages of
      their starvation and digestion with Fpg protein.

PMID- 9568585
TI  - Effect of vitamin C or beta-carotene on SCE induction by gamma rays in
      radiosensitized murine bone marrow cells in vivo.
AB  - The in vivo effect of vitamin C or beta-carotene on sister chromatid exchange
      (SCE) radio-induction was determined in murine bone marrow cells sensitized by
      BrdU incorporation. Pre- or post-treatment with 100 mg/kg body wt vitamin C did
      not cause a significant reduction in SCE induced by the exposure to 0.63 Gy gamma
      rays. Treatment with a double dose of vitamin C and with 0.45 Gy radiation did
      not cause a significant reduction in SCE frequency. However, due to the fact that
      vitamin C per se is capable of SCE induction, if an additive effect of radiation
      and vitamin C is considered, the expected frequency is higher than that observed.
      This implies that vitamin C could have a slight radioprotective activity. With
      regard to beta-carotene, it has been demonstrated that 50 mg/kg body wt causes a
      statistically significant increase per se, although pre- and post-treatment with
      the same dose has an additive effect on SCE frequency induced by 0.62 Gy
      radiation. This indicates that beta-carotene does not have radioprotective
      activity under the conditions used in the present study.

PMID- 9568586
TI  - Micronucleus induction in V79 cells after direct exposure to whole cigarette
      smoke.
AB  - Previous investigations on the effects of cigarette smoke on cultured cells have
      used mainly smoke condensate dissolved in culture medium. A system has been
      designed which allows direct exposure of cells to fresh cigarette smoke, without
      an intervening layer of growth medium between the cells and the smoke.
      Preliminary results have been obtained which demonstrate the viability of the
      system. V79 cells were cultured on porous membranes (Transwell; Costar). During
      smoke exposure only the lower surface of each Transwell is supplied with culture
      medium from the bottom of the culture chambers. In this way the cells had direct
      contact with the atmosphere at the upper surface and could be exposed directly to
      the test compound. The constructed exposure system consists of a smoke generator
      and an exposure unit containing six Transwells, the latter contained in an
      incubator. Cigarette smoke was generated using a standard 2 s, 35 ml puff once
      per min. The puff is diluted with conditioned air from the incubator and injected
      into the exposure unit. Following exposure of the cells to air only for 3 h there
      was no effect upon V79 cell viability. However, after exposure to smoke
      containing between 88 and 224 mg/m3 particulate matter, an inhibition of cell
      proliferation and induction of micronuclei was measured. When a Cambridge filter
      pad was placed between the cigarette and the cell exposure system to remove
      particulate matter cell proliferation was also reduced and an increased frequency
      of micronuclei above the control value was measured.

PMID- 9568587
TI  - Possible age-dependent adaptive response to a low dose of X-rays in human
      lymphocytes.
AB  - Human peripheral blood lymphocytes from 30 healthy donors aged from 5 to 65 years
      consisting of four groups, namely 5 (six males), 25 (six females), 45 (six males)
      and 65 years old (six males and six females), were exposed to a single adaptive
      dose of 0.01 Gy X-rays followed by a challenge dose of 2.0 Gy X-rays. All age
      groups responded with a significantly reduced incidence of chromatid and
      isochromatid breaks except Group 4 (65 years male and female groups), where
      adaptive and challenge doses did not significantly reduce chromatid and
      isochromatid breaks. Results indicate the possibility of an inducible chromosomal
      repair mechanism in human blood lymphocytes. It suggests that ageing could be a
      factor which abolishes the adaptive response.

PMID- 9568588
TI  - Absence of mutations in the highest mutability region of the p53 gene in tumour
      derived CHEF18 Chinese hamster cells.
AB  - A series of independent tumour-derived Chinese hamster CHEF18 cell lines was
      analyzed for the presence of mutations in the cDNA region (exons 5-9) of the p53
      gene, where the great majority of p53 mutations of human tumours accumulate.
      Since the gene is highly conserved among species, we used two primers designed on
      the basis of the human cDNA sequence to isolate the cDNA region from total RNA of
      Chinese hamster cells. The amplified fragments of 614 bp were digested with
      cleavase I endonuclease and fragment length polymorphism analysis showed that the
      restriction pattern of the p53 exons 5-9 region of tumour-derived cell lines was
      identical to that of diploid Chinese hamster CHL fibroblasts. Sequencing of the
      amplified fragments showed 100% homology between sequences, which demonstrated
      the absence of p53 mutations in the exons 5-9 cDNA region expected to have the
      highest mutability. Nevertheless, the antibody DO-7 recognized the presence of a
      stabilized p53 protein only in tumour-derived cell lines, which indicated that
      p53 expression correlated with transformed status.

PMID- 9568589
TI  - Comparative investigation on the mutagenicities of organophosphate, phthalimide,
      pyrethroid and carbamate insecticides by the Ames and lactam tests.
AB  - The Salmonella lactam test is a newly developed method for detecting genotoxins.
      This technique is based on the ability of DNA damaging agents to reverse
      expression of the beta-lactamase gene, an important gene that enables microbes to
      resist beta-lactam antibiotics. A construct p-SELECT Control DNA plasmid
      containing a beta-lactamase gene site was constructed in many mutant forms,
      including point and frameshift mutants. These mutant constructs were introduced
      into Salmonella tester strains whose mutagenicity is based on their ability to
      reverse expression of the beta-lactamase gene. Fourteen pesticides were evaluated
      for genotoxicity using our newly developed Salmonella typhimurium strains JK947
      and JK3, which are useful for detecting base substitution mutations. Six
      pesticides, namely allethrin, captan, folpet, monocrotophos, acephate and
      carbofuran, proved highly mutagenic in strain JK947, while the first four
      pesticides were more weakly mutagenic in strain JK3. In comparison, results from
      the Ames test show strain JK947 to be more sensitive to these pesticides than
      strains TA100 and TA1535. Strains TA98 and JK1 proved insensitive to allethrin,
      captan, folpet, acephate, carbofuran and monocrotophos. Among the many advantages
      of the lactam test are: large numbers of cells can treated and the test is
      operationally simple and inexpensive; revertant colonies form faster in the
      lactam test (16 h) than in the Ames test (48 h); the lactam test can detect
      mutagens present in biological specimens contaminated by histidine and biotin,
      samples that may give false positive results in the Ames test.

PMID- 9568590
TI  - Long-term effects of a change from a mixed diet to a lacto-vegetarian diet on
      human urinary and faecal mutagenic activity.
AB  - This is an investigation of the long-term effects of a shift from a mixed diet to
      a lacto-vegetarian diet and of a return to a mixed diet on the mutagenic activity
      in urine and faeces. The participants were 20 normal weight, non-smoking
      subjects. Dietary surveys and urinary and faecal samples were collected before
      and 3, 6 and 12 months after the dietary shift as well as 3 years after
      termination of the lacto-vegetarian diet period. The faecal samples were assayed
      for direct acting mutagens with the fluctuation test for weak mutagens and the
      urinary samples were assayed with the same assay but with a metabolic activation
      system, the so-called S9 fraction. The dietary data showed an increase in
      consumption of fruits, vegetables and dairy products and a decrease in meat,
      fish, eggs, sweets and biscuits during the vegetarian diet period. These changes
      led to an increase in total carbohydrates, fibre, vitamin C and calcium and a
      decrease in fat and protein intake. Mutagenic activity in both urine and faeces
      decreased after shift to the vegetarian diet and mutagenic activity in faeces
      increased when the volunteers returned to a mixed diet (P = 0.025 and 0.035
      respectively when comparing the diets). These data indicate that dietary factors
      may effect mutagenic activity in urine and faeces. However, it is still not clear
      whether a decrease in animal products, a change in other nutritional factors or a
      decrease in frying are the main contributors to this change.

PMID- 9568591
TI  - Induction of mutations by 2-acetylaminofluorene in lacI transgenic B6C3F1 mouse
      liver.
AB  - Mutations induced in liver cells by the hepatocarcinogen 2-acetylaminofluorene (2
      AAF) were characterized after i.p. administration on 4 consecutive days at 100
      mg/kg per injection in male B6C3F1 Big Blue transgenic mice that harbored the
      Escherichia coli lacI reporter gene. Animals were sacrificed at 5, 10 or 60 weeks
      following the last injection, livers removed and DNA packaged in vitro into
      bacteriophage lambda particles. The bacteriophage were assayed for lacI function
      by plating on E. coli in the presence of X-gal. Approximately 3 x 10(5) plaques
      were assayed per animal. Solvent-treated control mice exhibited a slight increase
      in mutant frequency over time, from 3.93 x 10(-5) at 5 weeks to 5.02 x 10(-5) at
      60 weeks. In contrast, treatment with 2-AAF yielded an approximately 2-fold
      increase in mutant frequency at 5 and 10 weeks after treatment relative to
      controls, with frequencies of 8.13 x 10(-5) and 7.43 x 10(-5) respectively.
      However, by 60 weeks post-treatment the mutant frequency was not significantly
      increased over concurrent controls. Similar to results in other systems, 2-AAF
      induced predominantly single base changes targeted to G:C base pairs, primarily
      G:C-->T:A transversions (27%). In contrast to results in other bacterial and
      eukaryotic systems, no deletions were observed among the 2-AAF-induced mutations
      and the 4 base hot spot deletion that is frequently observed in lacI in E. coli
      was not observed in this system, suggesting that the lacI transgene may be
      relatively refractory to frameshift mutations in vivo in the mouse.

PMID- 9568592
TI  - Microsomal metabolism and activation of the environmental carcinogen 2-amino-3
      methyl-9H-pyrido[23-b]indole.
AB  - 2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a mutagenic and
      carcinogenic heterocyclic amine formed as a pyrolysis product during cooking of
      food and combustion of tobacco. Hepatic microsomes from PCB-induced rats
      metabolized MeA alpha C to four products, of which three were non-mutagenic and
      one was mutagenic without S9 activation. The three non-mutagenic products, which
      accounted for 83% of the metabolism of MeA alpha C, were characterized by mass
      spectrometry and NMR spectroscopy as 6-hydroxy-MeA alpha C, 7-hydroxy-MeA alpha C
      and 3-hydroxy-methyl-A alpha C. The mutagenic metabolite, accounting for 17% of
      the metabolism of MeA alpha C, was characterized as N2-hydroxy-MeA alpha C by
      comparison with the HPLC retention time and UV spectrum of N2-hydroxy-MeA alpha C
      obtained by chemical synthesis. N2-Hydroxy-MeA alpha C was very reactive and a
      part of it bound covalently to microsomal proteins during incubation and a part
      was degraded to other products during incubation or chromatography. N2-Hydroxy
      MeA alpha C was mutagenic in Salmonella typhimurium TA98 without metabolic
      activation, resulting in 5070 revertants/microgram, which was > 20 times the
      specific mutagenic activity of the parent compound.

PMID- 9568593
TI  - Urinary mutagenicity on TA98 and YG1024 Salmonella typhimurium strains after a
      hamburger meal: influence of GSTM1 and NAT2 genotypes.
AB  - Mutagenicity on TA98 and YG1024 Salmonella typhimurium strains of pan-fried
      hamburger extracts and of 24 h post-meal urine from 32 non-smoking volunteers was
      evaluated. Each participant in the study was GSTM1 and NAT2 genotyped. After
      cooking the meat showed mutagenic activity (mean +/- SD) on strains TA98 and
      YG1024 of 114 +/- 129 and 1437 +/- 1536 net revertants/g respectively. Twenty
      three of 32 urine samples showed clear mutagenic activity (i.e. caused at least a
      doubling of the number of spontaneous revertants) on the O-acetyltransferase over
      producing strain YG1024, while none of the post-meal 24 h urine samples was
      clearly mutagenic on strain TA98. Total 24 h post-meal YG1024-active urinary
      mutagens were well correlated with the levels of mutagen intake with the meal (r2
      = 0.5977, F = 44.58, P < 0.01). In the group under study GSTM1 genotypes did not
      influence urinary mutagenicity. Highly exposed subjects (n = 15) with the NAT2-ss
      genotype showed significantly increased levels of urinary mutagenicity on strain
      YG1024 in comparison with NAT2-R subjects (mutagen intake-adjusted total 24 h
      mutagen excretion = 1.00 +/- 0.29 versus 0.66 +/- 0.32, Mann-Whitney U test, U =
      12.5, P < 0.05). Our results suggest that the levels of urinary mutagens derived
      from diets rich in heterocyclic aromatic amines, which are specifically detected
      by the YG1024 Salmonella strain, are modulated by NAT2-dependent enzyme activity,
      slow acetylators having higher levels of mutagens in their urine. Subjects with
      the rapid acetylator genotype, who are known to be at risk for colon cancer, seem
      to be partially protected with respect to the risk of bladder cancer.

PMID- 9568594
TI  - Spindle poisons can induce polyploidy by mitotic slippage and micronucleate
      mononucleates in the cytokinesis-block assay.
AB  - The human in vitro cytokinesis-blocked micronucleus (MN) assay has been
      extensively used for detection of clastogenic and aneugenic agents. In this test
      binucleate cells are generally considered to be the main target cell population
      for assessing genotoxic effect and almost no attention is paid to the biological
      information contained in mono-nucleate cells. In this study we analysed the
      frequencies of micronucleate mononucleates in a control population and after in
      vitro exposure to clastogens or aneugens. A clear increase in MN in mononucleates
      was found only after exposure to aneugenic compounds. By means of fluorescence in
      situ hybridization using a chromosome 1-specific probe we further analysed the
      proportion of mononucleate cells with and without MN which were tetrasomic
      (tetraploid) and would have been induced during aneugen treatment by mitotic
      slippage. The data indicate that treatment with nocodazole induces tetrasomy for
      chromosome 1 (tetraploidy) and an increase in MN frequency in mononucleate
      diploid and tetraploid lymphocytes. The results thus confirm that some
      mononucleates pass mitosis without chromatid segregation to daughter nuclei.
      These data suggest that MN in mononucleates may be useful to distinguish
      clastogens from aneugens and increase the sensitivity of the test.

PMID- 9568595
TI  - Induced somatic and germinal reversion of the white-spotted-1 insertional mutant
      phenotype in Drosophila melanogaster.
AB  - The white-spotted-1 (Wsp1) mutant of Drosophila melanogaster is characterized by
      the presence of an 8.7 kb retrotransposon (B104) inserted in the regulatory
      region of the white locus. The frequency of reversion in both somatic tissue and
      the germline after exposure to three different alkylating agents has been
      analysed. To determine if germinal revertants were induced by precise excision of
      the insertional element we analysed several phenotypic revertants using PCR and
      Southern blot techniques. The results indicate that, under our experimental
      conditions, the mutagens used did not induce excision of B104 in the white gene.
      In addition, the revertant phenotypes obtained were due to the existence of
      second site modifiers acting on expression of white. Such modifiers map near the
      white locus and, at least in one case, may correspond to suppressor-of-white
      spotted.

PMID- 9568596
TI  - [The 98th annual meeting of the Japan Surgical Society. Tokyo, Japan. April 8-10,
      1998. Abstracts].

PMID- 9568597
TI  - Obituary.

PMID- 9568598
TI  - Preparation for peripheral blood progenitor cell collection.

PMID- 9568599
TI  - Accurate analgesic dosing.

PMID- 9568600
TI  - Providing effective perineal-rectal skin care to patients with cancer.

PMID- 9568601
TI  - Better control of nausea and vomiting in transplant recipients.

PMID- 9568602
TI  - Paste helps alleviate diaper rash in pediatric population.

PMID- 9568603
TI  - At-risk for cancer: genetic discrimination in the workplace.
AB  - PURPOSE/OBJECTIVES: To discuss the complexity of issues related to genetic
      discrimination in the workplace against individuals identified as at risk for
      cancer. DATA SOURCES: Professional literature; local and national laws. DATA
      SYNTHESIS: A brief historical perspective on genetic discrimination is provided.
      Employment discrimination, insurance, job retention, and hiring issues facing
      cancer survivors and individuals genetically identified as at risk for cancer are
      discussed. State and federal initiatives that deal with these issues are
      examined, and strategies are proposed to prevent issues relating to genetic
      discrimination. CONCLUSIONS: Genetic discrimination, in all of its forms, is
      likely to emerge as a major challenge in the next century. IMPLICATIONS FOR
      NURSING PRACTICE: Oncology nurses must recognize new opportunities, assume new
      roles, and ready themselves for the challenges associated with this new kind of
      oncology nursing practice and the reality of genetic testing and disclosure.

PMID- 9568604
TI  - Patterns of exercise and fatigue in physically active cancer survivors.
AB  - PURPOSE/OBJECTIVES: To examine the physical activity patterns of cancer survivors
      who identify themselves as athletes to assess how much exercise athletic patients
      with cancer engaged in during treatment; to determine how cancer-related fatigue
      (CRF) affects athletic patients' ability to exercise, and to determine common
      problems and patterns associated with CRF experienced by athletic patients.
      DESIGN: Cross-sectional, descriptive survey. SETTING: International. SAMPLE: 219
      cancer survivors who responded to a call for subjects in four sports magazines.
      METHODS: Investigator-developed, mailed survey. FINDINGS: The majority of
      respondents were physically active before diagnosis and continued to exercise
      during their treatments with modifications in their activity level. Respondents
      exercised an average of nine hours per week. Sixty-nine percent of the
      respondents experienced problems with CRF during treatment, with 52% describing
      their CRF as affecting their whole body. Although 26% of the respondents felt
      most fatigued before exercise, exercise and rest were the most commonly used
      strategies for managing their symptoms. Patients with non-Hodgkin's lymphoma
      experienced significantly different CRF than patients with breast or prostate
      cancer and reported fewer benefits from exercise. CONCLUSIONS: The majority of
      respondents reported decreasing their activity level during treatment, but they
      believed that regular exercise would make them less likely to have health
      problems. Respondents used exercise both as an intervention to reduce CRF and as
      a means to have more energy. Patients with breast cancer reported more benefits
      from exercise than patients with non-Hodgkin's lymphoma. IMPLICATIONS FOR NURSING
      PRACTICE: The results provide indirect support for exercise as an intervention
      for CRF. Further research is needed to identify the optimal type and dose of
      exercise, clinical variables that influence the response to exercise, and the
      patients who will respond most favorably to exercise.

PMID- 9568605
TI  - Barriers to research utilization for oncology staff nurses and nurse
      managers/clinical nurse specialists.
AB  - PURPOSE/OBJECTIVES: To describe and compare barriers to research utilization
      faced by oncology staff nurses and nurse managers/clinical nurse specialists
      (CNSs) and to compare these to barriers identified by other nurses. DESIGN:
      Exploratory descriptive. SETTING: National. SAMPLE: Proportional random sample of
      2,000 Oncology Nursing Society (ONS) staff nurses (n = 769) from seven practice
      settings. ONS participants recruited oncology staff nurses (n = 331) and nurse
      managers/CNSs involved in cancer care (n = 407). METHODS: Mailings, including a
      demographic questionnaire and Barriers Scale, were sent to ONS nurses, and
      reminder postcards were sent to increase the return rate. MAIN RESEARCH
      VARIABLES: Barrier categories: characteristics of the adopter (nurse),
      organization, innovation (research itself), and communication, individual item
      barriers. Nurse and worksite characteristics. FINDINGS: Differences existed in
      oncology nurses' perceptions of the extent to which the adopter, organization,
      and innovation characteristics served as obstacles to research utilization. Nurse
      managers/CNSs perceived that each of these acted as a greater barrier than did
      staff nurses. Both groups perceived communication characteristics as a moderate
      barrier. Oncology nurses, as a group, responded similarly to other nurse samples
      regarding research and communication characteristics. Perceptions of oncology
      nurse managers/CNSs were similar to those of administrators in other studies.
      Oncology staff nurses rated barriers lower than nurses, including clinicians, in
      other samples. CONCLUSIONS: For oncology nurses, organization, research, and
      communication barriers persist as impediments to research utilization. Nurse
      adopter characteristics may be diminishing as obstacles for staff nurses but not
      for nurse managers/CNSs. The decreased strength that oncology nurses attributed
      to barriers may reflect a benefit of practicing nursing in a specialty.
      IMPLICATIONS FOR NURSING PRACTICE: Decreasing known barriers would facilitate
      research-based practice in oncology. Nurse leaders can create environments
      conducive to research utilization by altering existing mechanisms, facilitating
      access to nursing research experts, supporting time for research utilization
      efforts, giving authority for practice changes, and offering continuing education
      related to research utilization processes. Nurse managers/CNSs need to increase
      their familiarity with research and research utilization, ensuring their
      awareness of pertinent clinical findings. Perceptual gaps between staff nurses
      and nurse managers/CNSs regarding research utilization require discussion and
      formal investigation. Researchers must communicate in clinician-friendly ways.
      All nurses need to demand and facilitate access to research findings.

PMID- 9568606
TI  - Amifostine: drug profile and nursing implications of the first pancytoprotectant.
AB  - PURPOSE/OBJECTIVES: To review the drug profile and nursing implications of
      amifostine, a new cytoprotective agent. DATA SOURCES: Published articles,
      abstracts, professional communications, drug manufacturer, and personal
      experience with amifostine clinical studies. DATA SYNTHESIS: Amifostine increases
      the selectivity of specific anticancer agents for neoplastic cells by protecting
      normal tissue. It is indicated for reduction of the cumulative renal toxicity
      associated with repeated administration of cisplatin, in radiation therapy, and
      in several types of chemotherapies in patients with a variety of malignancies.
      Studies of amifostine used as a radioprotective and cytotoxic chemoprotective
      agent have demonstrated results against nephrotoxicity, neurotoxicity,
      hematotoxicity (granulocytopenia, leukopenia, and thrombocytopenia), and
      ototoxicity without adversely affecting tumor response or patient survival. The
      most common side effects are hypotension, nausea and vomiting (which may be
      severe), and a decrease in serum calcium concentrations. CONCLUSIONS: Amifostine
      is a new cytoprotectant, the first such agent with pancytoprotection. With
      appropriate management and premedication, amifostine is generally well-tolerated.
      Side effects are reversible following treatment discontinuation. IMPLICATIONS FOR
      NURSING PRACTICE: Nurses need to be knowledgeable about cytoprotectants, a new
      class of drugs, in order to teach patients and their families about the need for
      cytoprotection so they can comply with and participate in treatment plans and to
      identify the need for and management of amifostine administration. Patient-care
      concerns include the risk of decreased systolic blood pressure that requires
      fluid infusion and postural management and potentially severe nausea and
      vomiting.

PMID- 9568607
TI  - The impact of prostate cancer knowledge on cancer screening.
AB  - PURPOSE/OBJECTIVES: To test the effect of knowledge on participation in prostate
      cancer screening. DESIGN: Quasi-experimental design; PRECEDE framework. SAMPLE:
      319 men, 82% African American. METHODS: Prostate cancer knowledge was measured
      with a Prostate Cancer Knowledge Questionnaire prior to a community-based
      educational program. Men were referred to their personal physicians for a free
      prostate cancer screening. Results were sent to the Prostate Cancer Project. MAIN
      RESEARCH VARIABLES: Prostate cancer knowledge and participation in free prostate
      screening with a digital rectal examination and prostate specific antigen.
      FINDINGS: Prostate cancer knowledge was a predictor in participation in screening
      (p = 0.05). IMPLICATIONS FOR NURSING PRACTICE: Nurses need to target educational
      interventions for African American men, who have the highest incidence of and
      mortality rates for prostate cancer, to significantly reduce mortality rates.
      This study documented the importance of providing educational programs to
      increase participation in prostate cancer screening.

PMID- 9568608
TI  - Irinotecan hydrochloride: drug profile and nursing implications of a
      topoisomerase I inhibitor in patients with advanced colorectal cancer.
AB  - PURPOSE/OBJECTIVES: To review the drug profile and nursing implications of the
      topoisomerase I inhibitor irinotecan hydrochloride. DATA SOURCES: Published
      articles, abstracts, professional communications, drug manufacturer, and
      professional clinical experience with irinotecan clinical studies. DATA
      SYNTHESIS: Irinotecan, one of the first topoisomerase I inhibitors to gain wide
      clinical use, has exhibited activity in several malignancies. In June 1996, the
      United States Food and Drug Administration approved its use in patients with
      metastatic colorectal cancer refractory to fluorouracil (5-FU)-based therapy. The
      recommended starting dose is 125 mg/m2 administered as a weekly infusion for four
      weeks followed by a two-week rest period. The most common and clinically
      significant adverse events include diarrhea, neutropenia, and nausea and
      vomiting. Other adverse events include alopecia and fatigue. CONCLUSIONS:
      Irinotecan has significant activity in patients with 5-FU-refractory colorectal
      cancer. This drug is well tolerated and easily administered in an outpatient
      setting. The most common adverse events are well characterized and are reversible
      upon treatment discontinuation or dosage reduction. In particular, diarrhea, the
      most common toxicity, is manageable with use of appropriate dose modification and
      rigorous administration of loperamide at the first signs of diarrhea.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses need to focus on identifying and
      managing adverse effects based on individual patient tolerance. Nurses have an
      important role to play in patient education and follow up in order to minimize
      toxicity. Patient care concerns include management of diarrhea and nausea and
      vomiting, neutropenia with related risk of infection, and fluid and electrolyte
      imbalances.

PMID- 9568609
TI  - Nutritional assessment, intervention, and evaluation of weight loss in patients
      with non-small cell lung cancer.
AB  - PURPOSE/OBJECTIVES: To describe weight change in patients from the time of cancer
      diagnosis to the last healthcare encounter before death, to describe reported
      nutritional assessment, intervention, and evaluation; and to determine the
      relationship of weight change and cancer-related symptoms to nutritional
      assessment, intervention, and evaluation. DESIGN: Descriptive, correlational.
      SETTING: A National Cancer Institute-designated cancer center and its associated
      university medical center in the northeastern United States. SAMPLE: Medical
      records of 93 individuals with non-small cell lung cancer. METHODS: Retrospective
      chart review. MAIN RESEARCH VARIABLES: Weight change; nutritional assessment,
      intervention, and evaluation; and cancer-related symptoms. FINDINGS: Mean weight
      change from cancer diagnosis to last healthcare encounter was -4.75 kg (SD = 6.05
      kg). The mean regression slope of weight change was -3.69 kg/healthcare encounter
      (SD = 6.49 kg). The results of content analysis indicated that 90 subjects had
      nutritional assessments, 54 subjects had interventions, and 24 subjects had
      evaluations of intervention effectiveness. No association existed between weight
      change or cancer-related symptoms and nutritional assessment. Nutritional
      intervention was positively associated with dysphagia and depression, and
      evaluation of intervention effectiveness was positively associated with weight
      loss and dysphagia. CONCLUSIONS: Assessments of weight change and appetite
      usually were reported and appeared to be a routine part of patient care. However,
      assessments of weight loss and anorexia led to interventions only 60% of the
      time. When interventions were recommended, only 44% were evaluated for
      effectiveness. IMPLICATIONS FOR NURSING PRACTICE: Assessment of nutritional
      status needs to be broadened, interventions need to be initiated more often, and
      creative solutions to nutritional problems need to be sought. Regular evaluation
      of interventions is essential.

PMID- 9568610
TI  - Survivors of breast cancer: illness uncertainty, positive reappraisal, and
      emotional distress.
AB  - PURPOSE/OBJECTIVES: To explore variables associated with illness uncertainty and
      emotional distress for disease-free survivors of breast cancer. DESIGN: Cross
      sectional, descriptive, and correlational. SETTING: Regional cancer center in the
      southeastern United States. SAMPLE: 109 women one to six years post-treatment for
      stage I-III nonmetastatic breast cancer. METHODS: Face-to-face data gathering
      using five questionnaires with established reliability. MAIN RESEARCH VARIABLES:
      Symptom distress, concurrent illness, fear of recurrence, illness uncertainty,
      positive reappraisal, and emotional distress. FINDINGS: The antecedent variables
      symptom distress, fear of recurrence, and concurrent illness problems were
      positively related to illness uncertainty. Illness uncertainty and the antecedent
      variables were positively related to emotional distress. The antecedent variables
      explained 40% of the variance in uncertainty. Uncertainty, its antecedents, and
      positive reappraisal collectively explained 51% of the variance in emotional
      distress. CONCLUSIONS: Illness uncertainty related to symptoms and fear of
      recurrence was linked with emotional distress for some women, even years after
      treatment. Positive reappraisal may help to reduce this distress. IMPLICATIONS
      FOR NURSING PRACTICE: Nurses need to identify, monitor, and assist women who are
      at risk for illness uncertainty and emotional distress after breast cancer
      treatment. They also should explore with women positive, growth-promoting aspects
      of breast cancer, as well as aspects of the disease that are threatening.

PMID- 9568611
TI  - Autologous stem cell transplant plus interleukin-2 for breast cancer: review and
      nursing management.
AB  - PURPOSE/OBJECTIVES: To review the role of transplantation in breast cancer and
      describe the experience of one bone marrow transplant (BMT) program using
      autologous peripheral blood stem cell transplant (PBSCT) and interleukin-2 (IL-2)
      for the treatment of breast cancer. DATA SOURCES: Published articles, chart
      review, personal experience. DATA SYNTHESIS: Toxicities experienced by patients
      on this autologous PBSCT protocol that can be ascribed to low-dose IL-2 included
      nausea and vomiting, diarrhea, and skin rash. CONCLUSIONS: The most frequently
      occurring toxicities associated with low-dose IL-2 are not life-threatening. They
      do, however, affect the patient's quality of life and are toxicities that should
      be amenable to nursing interventions. IMPLICATIONS FOR NURSING PRACTICE: Oncology
      nurses must be aware of the side effects of different combination therapies
      (e.g., BMT, biotherapy). Nursing research is needed concerning the management of
      these toxicities when they occur because of combination therapies.

PMID- 9568612
TI  - Gender differences in the dimensions of quality of life.
AB  - PURPOSE/OBJECTIVES: To explore gender differences and similarities in the
      dimensions of quality of life (QOL). DESIGN: Secondary analysis of the
      Multidimensional Quality of Life Scale--Cancer Version (MQOLS--CA) data from two
      different research studies. SETTINGS: Multiple outpatient oncology sites. SAMPLE:
      The typical female participant (n = 254) was 58 years old (SD +/- 11.3) with 14
      years of education, married/partnered (64%), Caucasian (88%), and diagnosed with
      breast (47%) or colorectal (16%) cancer. The typical male participant (n = 222)
      was 60 years old (SD +/- 14) with 14.3 years of education, married/partnered
      (69%), Caucasian (85%), and diagnosed with colorectal (31%) or prostate (13%)
      cancer. METHODS: Factor analytic procedures and reliability testing. MAIN
      RESEARCH VARIABLES: QOL as measured by the MQOLS-CA, gender. FINDINGS: For women,
      two factors emerged from the analysis procedures-psychosocial well-being (7
      items) and physical competence (6 items). For the men, two different factors
      emerged--vitality (8 items) and personal resources (4 items). None of the cancer
      specific items from the MQOLS-CA loaded on any of the factors for either gender.
      CONCLUSIONS: Measurement of QOL requires gender-specific questions to accurately
      address the dimensions of the concept of QOL in females and males. IMPLICATIONS
      FOR NURSING PRACTICE: Additional research is warranted to replicate these
      findings. Gender-specific interventions could then be developed and tested to
      maximize the QOL of all patients.

PMID- 9568613
TI  - Ultrasonographic and serologic studies of experimental cysticercosis in rats
      infected with Taenia taeniaeformis.
AB  - Rats experimentally infected with Taenia taeniaeformis were followed-up until 14
      weeks post inoculation with eggs (PIE) by hepatic ultrasonographic (US) image and
      serum antibody response analyses. Parasitic cysts could be imaged as small (2 mm
      in diameter) anechoic areas with or without a parenthesis-like echogenic small
      line from two weeks PIE. Immunoblot analysis using antigens from oncospheres
      (TtO), 30-day-old (TtM-30) and 300-day-old metacestodes (TtM-300) revealed that:
      (1) these three different developmental stages showed their own unique patterns
      suggesting the presence of stage-specific antigens; (2) faint IgM antibody
      responses to some components of TtO and TtM-30 or TtM-300 could be detected from
      one and two weeks PIE, respectively, and (3) IgG responses to some major
      components of both TtO and TtM-300, and TtM-30 were easily detected from four and
      five weeks PIE onwards, respectively. Both TtO and TtM (especially TtM-300)
      appeared to be highly useful for detection of antibody responses in
      experimentally infected rats. Due to the easiness in preparation of antigens,
      fully developed metacestodes may be the best candidate antigens for
      serodiagnosis. These results strongly suggest that both US image and antibody
      analyses using antigens from fully developed metacestodes are useful for
      detection of the early stage of cysticercosis in laboratory animal model.

PMID- 9568614
TI  - A DNA vaccine protects mice against the rickettsial agent Cowdria ruminantium.
AB  - A DNA vaccine (VCL1010/MAP1) containing the major antigenic protein 1 (MAP1) gene
      of Cowdria ruminantium, driven by the human cytomegalovirus (HCMV) enhancer
      promoter, was injected intramuscularly into 8-10 week-old female DBA/2 mice after
      treating them with 50 microliters/muscle of 0.5% bupivacaine three days
      previously. Up to 75% of the immunized mice seroconverted and reacted with C.
      ruminantium antigen blots. Splenocytes from immunized mice, but not from control
      mice, proliferated in response to the recombinant MAP1 and to C. ruminantium
      antigens in in vitro lymphocyte proliferation tests. These proliferating cells
      secreted IFN-gamma and IL-2 at concentrations ranging from 610 pg/ml to 1290
      pg/ml and from 152 pg/ml to 310 pg/ml, respectively. Only up to 45 pg/ml and 42
      pg/ml of IFN-gamma and IL-2, respectively, were detected in supernatants of
      splenocytes from control mice. In experiments testing different VCL1010/MAP1 DNA
      vaccine dose regimens (25-100 micrograms/dose, two or four immunizations),
      survival rates of 23% to 88% (35/92 survivors/total in all VCL1010/MAP1 immunized
      groups) were observed on challenge with a lethal dose of cell culture-derived C.
      ruminantium organisms. In contrast, survival rates of 0% to 3% (1/144
      survivors/total in all control groups) were recorded for control mice. This study
      demonstrates that MAP1 is a protective antigen and validates the concept of DNA
      vaccines against heartwater.

PMID- 9568615
TI  - Induction of CD4+CD8+ double positive T cells and increase in CD5+ B cells in
      efferent lymph in sheep infected with Trypanosoma evansi.
AB  - The effects of Trypanosoma evansi on efferent lymphocyte phenotypes draining from
      a lymph node primed with Pasteurella haemolytica vaccine were studied in sheep.
      The prefemoral efferent lymphatic ducts of the infected sheep along with those of
      two uninfected sheep were surgically cannulated. Lymph was collected and
      lymphocytes recovered from it analysed by two-colour indirect immunofluorescence
      staining and cytofluoremetry in a fluorescence activated cell analyser (FACSCAN).
      The study showed the appearance and persistence of T. evansi in the efferent
      lymph for a long period of time and the appearance of CD4+CD8+ (double positive,
      DP) T lymphocytes in the efferent lymph of infected animals. The infection also
      resulted in increases in CD5+ B cells in the prefemoral efferent lymph. In
      addition, there were decreases in the output of conventional B cells, CD5+ and
      CD4+ T cell subsets but large increases in CD8+ cells followed by terminal
      depletion of all cell subsets. In contrast, inoculation of sheep with pasteurella
      vaccine antigen alone produced little alterations in the proportions, but large
      increases in the numbers of all T cell subsets except that of CD8+ cells which
      also showed little variation; and there was a concurrent increase in the numbers
      and proportions of efferent B cells. In addition, the abnormal expression of DP
      and CD5+ B cells did not occur in the uninfected vaccinated sheep. It is
      concluded that these abnormal changes in the kinetics of efferent lymphocyte
      phenotypes are likely to play a role in the genesis of the generalized
      immunosuppression seen in trypanosome-infected hosts.

PMID- 9568616
TI  - In vivo expression of cytokine mRNA in rats infected with Schistosoma mansoni.
AB  - As an animal model, rat schistosomiasis mansoni has provided considerable
      knowledge of immune mechanisms involved in the expulsion of worms and in a
      subsequent development of immunity to reinfection. Although it is clear that ADCC
      mechanisms participate in immunity to reinfection; the nature of the cytokines
      involved in immunity is unknown. To analyse the pattern of cytokines involved,
      the mRNA levels of different cytokines were assessed by RT-PCR as they occur
      within tissues during the course of infection. In spleens from infected rats, a
      significant elevation in IL-2 and IL-5 mRNA was observed during the early phase
      of infection (day 7). Analysis of pulmonary cytokine responses showed a dramatic
      increase in IL-4 and IL-5 on day 7. This was accompanied with a low but
      significant increase in IL-2 (day 11) and IL-12 (day 7) in the absence of
      augmented IFN-gamma expression. The cytokine expression patterns of draining
      lymph nodes (LN) from infected rats showed a significant increase of IL-2, IL-4
      and IL-5 on day 21. Analysis of IL-10 expression showed exclusively a significant
      increase in LN on day 11, IFN-gamma mRNA was not detected in any tissue sample.
      Thus, rats develop a predominately Th2-type cytokine response during a primary
      infection which may be involved at least in part, in the expression of immunity
      against Schistosoma mansoni infection.

PMID- 9568618
TI  - A pediatrician's view. The skin game.

PMID- 9568617
TI  - Murine Schistosoma bovis infection: analysis of parasitic and immune parameters.
AB  - Humoral and cellular responses to Schistosoma bovis antigens have been evaluated
      over a period of 11 weeks in mice exposed to S. bovis cercariae and data analysed
      in the context of the parasitic parameters (worm and egg loads) recorded at days
      30, 60 and 80 of the ongoing infection. Results revealed a decrease of worm
      burden, particularly marked for female worms, between day 60 and day 80 of
      infection suggesting a higher susceptibility of female schistosomes to attrition
      mechanisms. The B-cell response, studied by measuring the production of different
      isotypes, was directed against different stage specific antigens, with a
      predominance of IgG1 antibodies associated with a significant increase of IgA and
      IgE antibodies after egg deposition. The T-cell response, assessed after in vitro
      stimulation of splenocytes, showed a predominant production of Th-2 cytokines (IL
      4, IL-5 and IL-10) occurring after egg laying. Interestingly in contrast to S.
      mansoni infection the Th-2 polarization did not seem to be exclusively triggered
      by egg-associated antigens since significant amounts of IL-10 were produced after
      stimulation with adult worm antigen preparation (SWAP) before the beginning of
      egg deposition.

PMID- 9568619
TI  - Pediatric dermatoses commonly seen, uncommonly recognized.

PMID- 9568620
TI  - When it's not ringworm: annular lesions of childhood.

PMID- 9568621
TI  - Congenital midline lesions: pits and protuberances.

PMID- 9568622
TI  - Exanthems in childhood: an update.

PMID- 9568623
TI  - Principles of topical therapy.

PMID- 9568624
TI  - Antifungal therapy in children: an update.

PMID- 9568625
TI  - Effect of recirculation of 99mTc-Sn colloid in estimating mean transit time of
      soft-tissue vascular anomalies by direct puncture scintigraphy: a simulation
      analysis.
AB  - We have reported direct puncture scintigraphy, a novel method to estimate mean
      transit time (MTT) of soft-tissue vascular anomaly. In the examination, 99mTc-Sn
      colloid is infused percutaneously into the lesion, and MTT is calculated using
      the time-activity curve for the lesion. Recirculation of 99mTc-Sn colloid is
      neglected in computing MTT, and this may cause error. The aim of this study was
      to assess this error by simulation analysis. Data simulating direct puncture
      scintigraphy were produced for lesions with various blood volumes and various
      blood flows, considering recirculation and blood clearance of 99mTc-Sn colloid,
      and MTT was estimated by the same method used in the patient examination.
      Although MTT was overestimated in large lesions with intermediate or long MTT,
      the error was small except in extremely large lesions. It was suggested that
      recirculation of 99mTc-Sn colloid does not cause a serious problem in the
      clinical use of direct puncture scintigraphy.

PMID- 9568626
TI  - Development of a 3D CT-scanner using a cone beam and video-fluoroscopic system.
AB  - We describe the design and implementation of a system that acquires three
      dimensional (3D) data of high-contrast objects such as bone, lung, and blood
      vessels (enhanced by contrast agent). This 3D computed tomography (CT) system is
      based on a cone beam and video-fluoroscopic system and yields data that is
      amenable to 3D image processing. An X-ray tube and a large area two-dimensional
      detector were mounted on a single frame and rotated around objects in 12 seconds.
      The large area detector consisted of a fluorescent plate and a charge coupled
      device (CCD) video camera. While the X-ray tube was rotated around the object, a
      pulsed X-ray was generated (30 pulses per second) and 360 projected images were
      collected in a 12-second scan. A 256 x 256 x 256 matrix image was reconstructed
      using a high-speed parallel processor. Reconstruction required approximately 6
      minutes. Two volunteers underwent scans of the head or chest. High-contrast
      objects such as bronchial, vascular, and mediastinal structures in the thorax, or
      bones and air cavities in the head were delineated in a "real" 3D format. Our 3D
      CT-scanner appears to produce data useful for clinical imaging and 3D image
      processing.

PMID- 9568627
TI  - Lipiodolized gelatin sponge: a simple method to make gelatin sponge radiopaque.
AB  - Gelatin sponge particles were rendered radiopaque by soaking them in small
      amounts of iodized oil (LP-GS). They were evaluated for their usefulness in
      transarterial embolization (TAE). The LP-GS particles were well visualized
      fluoroscopically during TAE. The duration of the opacity of LP-GS exceeded 24
      hours both in vitro and in vivo. LP-GS are useful, and are an easily obtainable,
      radiopaque, embolic material.

PMID- 9568628
TI  - Pulmonary arteriovenous fistula: long-term results of percutaneous transcatheter
      embolization with spring coils.
AB  - PURPOSE: The aim of this study was to assess the effectiveness of percutaneous
      treatment of PAVFs through the results of long-term follow-up. PATIENTS AND
      METHODS: Transcatheter embolization of PAVFs using spring coils was performed in
      seven patients (six women and one man) with nine PAVFs, between 1989 and 1995,
      who were followed up at least one year. The size of the nine PAVFs ranged from 4
      mm to 70 mm in diameter (mean 26 mm). Two fistulas were huge, 70 x 45 mm and 60 x
      65 mm in diameter. Embolization was performed twice in three patients and once in
      four patients. In the two patients with huge PAVFs, after anchoring metallic
      "spiders" into the feeding artery, the largest coils were positioned and
      entangled with the "spider" followed by the placement of smaller coils to fill in
      the center of the feeding artery. RESULTS: No severe complications were seen in
      the short-term follow-up. Arterial oxygen pressure improved in all patients with
      low oxygen pressure. Five patients with seven fistulas, six of which disappeared
      on chest X-ray film, are still alive after follow-up ranging from one year and 10
      months to seven years and nine months. The two patients with huge fistulas died
      more than one year after treatment, one of hemoptysis of the contralateral lung
      and the other of pulmonary fibrosis. CONCLUSION: Complete embolization of a
      medium-sized feeding artery can cure this anomaly.

PMID- 9568629
TI  - Totally occluded iliac arteries: long-term results of percutaneous transluminal
      angioplasty.
AB  - PURPOSE: To evaluate the initial and long-term results of percutaneous
      transluminal angioplasty (PTA) for totally occluded iliac arteries. METHODS:
      Fifty-four occluded iliac arteries in 54 patients were treated by PTA. The mean
      length of the occlusions was 8.0 cm (range 0.5-24.0 cm). Patients were followed
      for a maximum of 124 months (mean, 56 months). RESULTS: The initial success rate
      was 57% (31 of 54). On follow-up study, two arteries were reoccluded, and six
      showed evidence of restenosis. These recurrences were observed within 20 months
      after PTA. The long-term results obtained by Kaplan-Meier life-table analysis
      revealed a 71% primary patency rate and 93% secondary patency rate for 124
      months. Thirteen arteries were treated by surgical intervention, while the other
      arteries with unsuccessful PTA were followed conservatively because of a high
      risk for surgery or patients' refusal to have surgery. Major complications were
      recorded in 7% (4 of 54) of cases: thrombosis requiring emergent bypass surgery
      in one artery, and distal embolization requiring thromboembolectomy in three.
      CONCLUSION: Although the procedure is difficult, the long-term results suggest
      that PTA is an effective method and a treatment of choice for totally occluded
      iliac arteries.

PMID- 9568630
TI  - Analysis of treatment results of hypopharyngeal cancer.
AB  - Sixty-three patients with squamous cell carcinoma of the hypopharynx were treated
      at the University of Tokyo between 1985 and 1993. Twelve patients were treated
      with surgery alone, 16 with preoperative irradiation, 26 with postoperative
      irradiation, and nine with irradiation alone. A tumor dose of 50 Gy (25
      fractions/5 weeks) was used in postoperative irradiation, 40-60 Gy in
      preoperative irradiation, and 70 Gy in irradiation alone. When "number of
      indications," including, for example, partial pharyngectomy, positive or close (<
      or = 5 mm) margin, and extracapsular extension, was used for multivariate
      analysis in patients who underwent surgery, it proved to be the only significant
      prognostic factor for gross survival. Six of seven patients with a positive
      surgical margin or close margin who received postoperative irradiation had local
      recurrence. A tumor dose of 50 Gy (25 fractions/5 weeks) in postoperative
      irradiation is not enough. It is difficult to cure by irradiation metastases to
      the parapharyngeal lymph nodes large enough to be detected with CT. It is
      necessary to irradiate parapharyngeal lymph nodes prophylactically, but 50 Gy in
      postoperative irradiation may not be enough from our results. The same may be
      true for metastases to the paratracheal nodes, which lie close to the lower poles
      of the thyroid gland or within the superior mediastinum and are difficult to
      access through surgery. In the patients who were operated on, N stage and the
      number of lymph node metastases were significant for gross survival. When "number
      of indications" was used for analysis, "number of indications" proved to be the
      most significant prognostic factor for gross survival.

PMID- 9568631
TI  - CD34-positive cell yield in peripheral blood of cancer patients during radiation
      therapy.
AB  - For the purpose of evaluating the feasibility of inducing CD34-positive cells in
      peripheral blood by radiation therapy, we examined the changes in CD34-positive
      cells in 21 cancer patients (16 with lung cancer and five with esophageal cancer)
      during thoracic radiotherapy using flow cytometry and CD34 monoclonal antibody.
      Although assays of granulocyte-colony-forming units (G-CFU) and granulocyte
      monocyte-colony-forming units (GM-CFU) were also performed for 16 of the patients
      during radiation therapy, in most of these cases there was approximately one G
      CFU or GM-CFU for every 100 CD34-positive cells. Seven of the 21 cancer patients
      showed percentages of CD34-positive cells of more than 3% (more than mean + 2
      S.D.; standard deviation) of mononuclear cells in peripheral blood in at least
      one of the examinations. However, six of these seven patients were in stage IV
      with distant metastases (four with lung cancer and two with esophageal cancer),
      and another lung cancer patient was in stage III. Therefore, CD-34 positive cells
      were shown to appear in peripheral blood especially in the patients with advanced
      stages of malignancy, and further examinations are needed to induce CD34-positive
      cells by radiation therapy for possible application of ultra-high dose
      chemotherapy supported by peripheral blood stem cell transplantation.

PMID- 9568632
TI  - The relative biological effectiveness of the modulated proton beam at TRIUMF.
AB  - PURPOSE: The purpose of this study was to determine the relative biological
      effectiveness (RBE) of proton beam and to study its dependency on fraction
      number. METHODS: The relative biological effectiveness (RBE) of fractionated
      protons compared with 60Co gamma-rays was investigated for the acute mouse skin
      reaction. The 80 MeV protons generated at the TRIUMF cyclotron were spread out
      from 7 to 25 mm to irradiate entire legs. One, two, four, and eight fractions
      were tested. RESULTS: RBE values ranged from 1.15 to 1.24 for the acute skin
      reaction. Fraction dose dependence of RBEs was not observed.

PMID- 9568633
TI  - Inflammatory pseudotumor of the spleen: US and MRI findings.
AB  - The ultrasound and color Doppler sonography characteristics of inflammatory
      pseudotumor (IPT) of the spleen are nonspecific, and thus preoperative diagnosis
      of the tumor is difficult. We describe a case of IPT of the spleen studied with
      ultrasound, color Doppler sonography, CT, and MRI, and we report the usefulness
      of US and MRI findings of the tumor.

PMID- 9568634
TI  - A case of enlarged cavernous sinus mistaken for petrous apex tumor.
AB  - We experienced a case of abnormally enlarged cavernous sinus extending into the
      petrous apex, which was confused with a petrous apex tumor or an enlarged Meckel
      cave. The CT and MR appearances were of expansile lesions in the petrous apex
      with water signal intensities on both T1- and T2-weighted MR images.
      Unfortunately, these findings were not specific. Cerebral angiography was only
      suggestive of enlarged cavernous sinus involving the petrous apex because of
      opacification of the petrous apex in the venous phase. Our case was confirmed by
      surgery as enlarged cavernous sinus involving the petrous apex.

PMID- 9568635
TI  - Secondary angiosarcoma following irradiation--case report and review of the
      literature.
AB  - Angiosarcoma is a rare malignant tumor that accounts for 1% to 2% of all soft
      tissue sarcomas. This paper reports a case of radiation-associated angiosarcoma
      with a literature review of 66 cases. Twenty-nine years after transabdominal
      hysterectomy and adjuvant radiation therapy for uterine cervix cancer, cutaneous
      angiosarcoma developed in the abdominal wall of a 63-year-old woman. She
      underwent wide excision of the abdominal wall mass, radiation therapy, and
      chemotherapy, and has been alive and well without any evidence of metastasis for
      23 months since the initial diagnosis of angiosarcoma. After an intensive
      literature review, we found 66 cases of radiation-associated angiosarcoma. The
      most common primary disease was breast cancer (44%), with gynecologic cancer
      (21%) next. Eighty-five percent of radiation-associated angiosarcomas developed
      in the cutaneous area. The median age at diagnosis was 65 years, and the median
      latency period from irradiation to diagnosis was 96 months. The median survival
      period of 48 patients whose survival lengths could be reviewed was 12 months.

PMID- 9568636
TI  - Focal fatty infiltration in the quadrate lobe of the liver accompanied by
      aberrant right gastric vein.
AB  - Focal fatty liver in the posterior edge of the quadrate lobe was observed in a 59
      year-old woman. This lesional portion was nourished by the aberrant right gastric
      vein, not by the main portal vein. This abnormality in portal blood flow was
      suspected to be one of the causes of the focal fatty liver.

PMID- 9568637
TI  - Case report: MR findings of a retained surgical sponge.
AB  - We describe here a case in which a retained surgical sponge progressed into the
      perirenal space and posterior pararenal space from the pelvic cavity. Sonography,
      CT, and T1-weighted MR image analyses could not show clearly the characteristic
      structure of the surgical sponge, but T2-weighted MR imaging showed a folded
      fabric appearance within the cystic mass. Surgical findings confirmed a lobulated
      cystic mass containing yellowish fluid and a surgical sponge.

PMID- 9568638
TI  - Regulation of tissue-degrading factors and in vitro invasiveness in progression
      of breast cancer cells.
AB  - Hormone-independent growth and invasiveness represent phenotypic properties
      acquired during early progression of breast cancer. We compared human mammary
      adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic,
      with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with
      regard to expression of tissue-degrading factors of the matrix metalloproteinase
      (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in
      vitro invasive properties. Both cell lines showed low constitutive mRNA
      expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was
      also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher
      (approximately 10-fold). Furthermore, both cell lines revealed low constitutive
      capacity to migrate in an in vitro invasion assay. Treatment with 12-O
      tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as
      well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, amongst
      which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels
      of MMP-9 and PAI-1 were approximately 10-fold and approximately 15-fold higher in
      MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immunoreactive PAI-1
      was considerably elevated (> 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the
      TPA-dependent level of 92-kDa MMP-9 was only approximately 2-fold higher in
      MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was
      associated with an increase (approximately 10-fold) in in vitro migration, which
      in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement
      membrane extract (Matrigel). These data suggest that TPA-responsive in vitro
      invasive properties that are probably associated with PAI-1 expression may co
      vary with progression from hormone-dependent to -independent breast cancer.

PMID- 9568639
TI  - Chemically modified tetracyclines inhibit human melanoma cell invasion and
      metastasis.
AB  - Recent work has shown that chemically modified tetracyclines (CMTs) are potent
      inhibitors of matrix metalloproteinase (MMP) activity, both in vitro and in vivo,
      which is distinct from their antimicrobial activities (Golub et al. Crit Rev Oral
      Biol Med, 2, 297-321, 1991; Ryan et al. Curr Opin Rheumatol, 8, 23847, 1996). The
      process of tumor cell invasion requires MMP-mediated degradation of extracellular
      matrix barriers as a key step in the metastasic cascade. In this study, we
      examined the effect(s) of doxycycline and CMTs on extracellular levels of
      gelatinase A and B activity from a highly invasive and metastatic human melanoma
      cell line C8161, and correlated these observations with changes in the cells'
      biological behavior in an in vitro invasion assay and in an in vivo SCID mouse
      model. The results indicate that coincident with the ability of these compounds
      to differentially suppress extracellular levels of gelatinase activity, C8161
      cells treated with doxycycline, CMT-1, CMT-3, or CMT-6 were less invasive in
      vitro in a dose-dependent manner (3-50 microg/ml). Furthermore, data derived from
      the in vivo model indicate that SCID mice dosed orally with CMT-1 or CMT-3
      contained a reduced number of lung metastases following i.v. injection of C8161
      cells via tail vein inoculation. These observations suggest that careful
      screening of different CMTs could lead to the identification of compounds which
      suppress the formation and magnitude of metastases associated with certain
      cancers, and if used as an adjunct to other treatment regimes, lead to greater
      efficacy in the treatment of metastatic cancers.

PMID- 9568640
TI  - Thymosin beta15 expression in tumor cell lines with varying metastatic potential.
AB  - We previously isolated thymosin beta15 from highly metastatic Dunning rat
      prostatic carcinoma cells. Immunohistochemical study of human prostate cancer
      specimens revealed a general correlation between Gleason grade and thymosin
      beta15 expression, with high-grade (more malignant) tumors showing increased
      staining compared to low-grade tumors. To determine whether thymosin beta15 may
      be differentially expressed in cancer cells with different metastatic potential
      other than in the prostatic carcinoma cells, we examined thymosin beta15 mRNA
      levels in tumor cell lines from different species. We also examined thymosin
      beta15 protein levels in human breast cancer samples. Thymosin beta15 was
      upregulated in the highly metastatic mouse lung and human breast cancer cell
      lines in comparison to the nonmetastatic counterparts. Immunohistochemical
      staining showed the evidence of upregulation of thymosin beta15 in malignant
      human breast carcinomas as compared to benign breast tumors. The expression of
      thymosin beta15 was correlated with the metastatic potential of the mouse lung
      carcinoma and human breast carcinoma cells in addition to the prostatic
      carcinomas. Thymosin beta15 may be a useful marker to predict metastatic
      potential of certain human cancers.

PMID- 9568641
TI  - The influence of antiestrogens on the release of plasminogen activator (uPA) by
      MDA-MB-231 and MCF-7 breast cancer cells.
AB  - Plasminogen activators are known to be involved in the metastatic spread of
      breast cancer. In the present study we examined the effects of antiestrogens
      [Analog II (1,1-dichloro-cis-2,3-diphenyl cyclopropane) (AII), ICI-182,780 (ICI)
      and tamoxifen (TAM)], on the in vitro release of uPA from estrogen receptor (ER)
      positive MCF-7 (MCF) and ER-negative MDA-MB-231 (MDA) human breast cancer cell
      lines. Using a solid-phase radioassay, uPA activity was found to be higher in the
      culture medium from MDA cells compared to MCF cells. Aminocaproic acid, a
      specific plasmin inhibitor, produced a 50-60% reduction in the degradation of
      labeled substrate, in the solid phase assay, using culture medium from both cell
      lines, thus indicating that most of the proteolysis observed was due to uPA
      mediated plasmin generation from plasminogen. In the absence of plasminogen, the
      enzyme activity was not detected in either the quantitative assay or by
      zymography. In MDA cells, uPA release was not altered by any of the antiestrogens
      used alone or in the presence of estradiol. In contrast, in MCF cells, ICI alone
      produced maximal inhibition (40%) of enzyme release, while estradiol alone
      produced a 120% increase in enzyme activity. When co-administered with estradiol,
      in MCF cultures, each antiestrogen reduced enzyme activity to control levels.
      Substrate gel zymography revealed that the urokinase-type PA is the predominant
      form of PA released by both cell lines. Comparison of the activity of all three
      antiestrogens used in this study indicates that ICI is the most potent inhibitor
      of enzyme activity in ER-positive MCF cells.

PMID- 9568642
TI  - Down-regulation of focal adhesion kinase, pp125FAK, in endothelial cell
      retraction during tumor cell invasion.
AB  - Although endothelial cell retraction is required before tumor cell invasion, its
      molecular mechanism still remains obscure. We previously demonstrated that
      conditioned medium (CM) derived from a human pancreatic cancer cell line, PSN-1,
      induced endothelial cell retraction and facilitated tumor cell invasion. To
      investigate the molecular change of events in the transduction of extracellular
      signals during endothelial cell retraction, we examined the effect of the CM
      derived from PSN-1 cells on the tyrosine phosphorylation in endothelial cells.
      Immunoblot analyses revealed that the PSN-1 CM decreased tyrosine phosphorylation
      of a 120-130 kD protein, and induced the concomitant down-regulation of focal
      adhesion kinase, pp125FAK, during endothelial cell retraction in time- and dose
      dependent fashions. These changes preceded endothelial cell retraction and were
      reversible after removal of the CM. Further quantitative densitometric analyses
      demonstrated that the extent of decrease in tyrosine phosphorylated 120-130 kD
      protein during the endothelial cell retraction was likely to be proportional to
      that of the down-regulation of pp125FAK. A tyrosine phosphorylated 120-130 kD
      protein immunoprecipitated by anti-phosphotyrosine antibody immunoreacted with
      anti-pp125FAK antibody. These results suggested that decreased amount of a
      tyrosine phosphorylated 120-130 kD protein probably due to the down-regulation of
      pp125FAK might be associated with the signal transduction pathway in the
      endothelial cells during their retraction. Furthermore, these findings were also
      observed in the CM from another four human cancer cell lines, suggesting the down
      regulation of pp125FAK in endothelial cells during tumor cell invasion.

PMID- 9568643
TI  - C-met activation is necessary but not sufficient for liver colonization by B16
      murine melanoma cells.
AB  - Metastasis to the liver is a frequent event in clinical oncology, the molecular
      mechanisms of which are not fully understood. We have recently reported a
      consistent overexpression of c-met in B16 melanoma cells selected in vivo for
      enhanced liver metastatic ability. In this study we address the question as to
      whether constitutive activation of c-met is a necessary and sufficient condition
      for enhanced liver colonization by B16 melanoma cells. Different levels of c-met
      expression and/or activation in B16 cells were achieved by subcloning, or by c
      DNA transfection with either HGF/SF or the oncogenic form of c-met (tpr-met).
      Metastatic ability of the different populations was then evaluated in vivo by the
      lung colonization (experimental metastasis) assay. Results indicate that c-met
      (but not tpr-met) activation in B16 melanoma cells may increase their liver
      colonizing potential, probably by enhancing motility and invasion in response to
      paracrine interactions with its ligand. C-met expression per se, however, is not
      able to change the organ specificity of the cells. C-met activation appears
      instead to be required at later stages of liver colonization by B16 melanoma
      cells, in order to enhance their site-specific metastatic ability.

PMID- 9568644
TI  - Enhancement of type IV collagenases by highly metastatic variants of HT1080
      fibrosarcoma cells established by a transendothelial invasion system in vitro.
AB  - A novel in vitro invasion assay system was established in this laboratory, in
      which the invasion of tumor cells after interaction with endothelial cells could
      be examined. Two variant cell lines (FP-10, FP-21) were established from parental
      HT1080 cells using this assay system. FP-10 and FP-21 cells had higher invasive
      and metastatic potential than the parental cells both in vitro and in vivo. The
      activity of anchorage-independent proliferation and the adhesion to the HUVEC
      monolayer of FP-10 and FP-21 was greater than the parental cells. The secretion
      of type IV collagenase (both MMP-2 and MMP-9) was also increased more
      significantly by the variant cells than by the parental cells, and the expression
      of uPA mRNA was higher in FP-10 and FP-21. Treatment of variant cells with human
      TIMP-2 remarkably suppressed the increment of the in vitro invasion to the same
      level as parental cells. These results suggest that this in vitro
      transendothelial invasion system accelerates multiple mechanisms of the
      metastasis by HT1080, especially the production of type IV collagenases. It can
      thus provide a useful model of tumor metastasis.

PMID- 9568645
TI  - Failure of tumor-reactive lymph node cells to kill tumor in the presence of
      immune-suppressive CD34+ cells can be overcome with vitamin D3 treatment to
      diminish CD34+ cell levels.
AB  - Growth of Lewis lung carcinoma (LLC-LN7) tumors results in an increase in CD34+
      granulocyte-macrophage progenitor cells having natural suppressor (NS) activity.
      These CD34+ NS cells were capable of inhibiting the cytotoxic activity of tumor
      reactive lymph node cells. In vivo studies showed that adoptive treatment of LLC
      LN7 tumor-bearing mice with tumor-reactive lymph node cells plus IL-2 failed to
      reduce the development of metastases. Studies were conducted to determine if
      diminishing the levels of CD34+ NS cells would allow for improved anti-tumor
      effectiveness of the adoptively transferred cells. The suppressive activity of
      CD34+ cells toward the cytolytic activity of tumor-reactive lymph node cells
      could be blocked by in vitro culture of CD34+ cells with the differentiation
      inducing hormone 1alpha,25-dihydroxyvitamin D3. Similarly, treatment of LLC-LN7
      bearing mice with vitamin D3 alone diminished the levels of CD34+ NS cells within
      regional lymph nodes, spleens and tumors. This treatment resulted in an increased
      immune reactivity to autologous tumor, as shown by the production of IFN-gamma by
      lymph node cells in response to the presence of LLC-LN7 cells. The extent of
      tumor metastasis in mice receiving vitamin D3 treatment was also reduced. When
      tumor-reactive lymph node cells were adoptively transferred into these LLC-LN7
      bearing mice that were receiving vitamin D3 treatment, there resulted a
      pronounced synergistic reduction in tumor metastasis. The results of this study
      show that treatment of tumor bearers with vitamin D3 to eliminate CD34+ NS cells
      improves the anti-tumor effectiveness of adoptively transferred tumor-reactive
      lymph node cells.

PMID- 9568646
TI  - Induction of heat shock protein 27 by hydroxyurea and its relationship to
      experimental metastasis.
AB  - Treatment of tumor cells with hydroxyurea (HU) has been shown to increase the
      experimental metastatic potential of these cells. We have previously described
      the induction of stress proteins (antioxidants) by HU in B16 murine melanoma
      cells and their relationship to the metastatic process. We have now investigated
      the induction by HU of another set of stress proteins, the heat shock proteins,
      and their role in experimental metastasis. HU markedly increased the cellular
      content of heat shock protein (hsp) 27 but not of hsp 90, 72/73, or 60 as
      measured by immunoblotting. The induction of hsp27 protein was preceded by a
      specific increase in hsp27 mRNA. Furthermore, HU-treated cells were more
      thermotolerant. To investigate the functional role of hsp27, human hsp27 cDNA was
      constitutively overexpressed in B16 cells at levels seen in HU-treated cells. In
      separate experiments, we induced a global increase in hsps by heat shock. Neither
      the hsp27 transfectants nor the heat-shocked cells demonstrated an increase in
      their experimental metastatic capacity. We conclude that hsp27 protein is
      increased by HU by the specific induction of hsp27 mRNA in B16 melanoma cells but
      increased hsp27 protein is not responsible for the increase in experimental
      metastasis. Since high levels of hsp27 are associated with metastatic disease in
      breast and ovarian cancers, but not in our experimental system, the functional
      role of hsp27 in metastasis requires further study.

PMID- 9568647
TI  - Characterization of the progressive sublines derived from a weakly malignant
      cloned cell line, ER-1, co-inoculated subcutaneously with a foreign body.
AB  - We previously established an experimental model of tumor progression using a
      weakly malignant rat mammary carcinoma cell line, ER-1. Using this model, we
      demonstrated that ER-1 cells converted into highly tumorigenic and metastatic
      cells, ERpP, by s.c. co-inoculation with plastic plates. We here compared in
      vitro biological properties associated with malignancy of ER-1 cells with those
      of ERpP cells which were highly malignant when inoculated into syngeneic rats. In
      vitro growth rate of ERpP cells was higher than that of ER-1 cells under a low
      nutrient condition. Invasion capacity of ERpP cells to rat lung endothelial cell
      monolayer or reconstituted basement membrane, Matrigel, was higher than that of
      ER-1 cells. Migration of ERpP cells toward fibronectin or laminin was also
      significantly higher than that of ER-1 cells. There was no difference in
      gelatinolytic or plasminogen activator activity detected in conditioned media
      between ER-1 and ERpP cells. Furthermore, we found that ER-1 cells communicated
      better among themselves and with normal fibroblasts through gap junctions
      compared to ERpP cells. These results suggest that growth advantage in a poor
      nutrient condition, enhancement of cell motility, and loss or decrease of
      junctional communication may be associated with tumor progression of ER-1 cells.

PMID- 9568648
TI  - Electric cautery lowers the contamination threshold for infection of
      laparotomies.
AB  - BACKGROUND: Interplay between wound resistance factors and bacterial innoculum
      determines the risk of surgical infection. Since cautery causes more damage than
      the scalpel, our hypothesis is that lower numbers of bacteria are required to
      infect wounds made by electric cautery than to infect wounds made with a scalpel.
      METHODS: Abdominal fascia was incised in 375 rats by cold knife, cutting current,
      or coagulation current. Wounds were innoculated with increasing numbers of
      bacteria and histologically scored at 7 days for necrosis, inflammation, and
      abscess. RESULTS: Coagulation current causes more inflammation, necrosis, and
      abscesses than the scalpel at all bacterial levels. Electric cutting current is
      intermediate, causing more damage than the scalpel only after contamination
      reached 10(5). Above this threshold most wounds were infected in all groups.
      CONCLUSIONS: Electric coagulation current should be used only when the need for
      meticulous hemostasis outweighs the considerably increased risk of infection.
      Electric cutting current is less destructive but also less hemostatic;
      indications for its use are difficult to identify.

PMID- 9568649
TI  - Is abdominal cavity culture of any value in appendicitis?
AB  - BACKGROUND: Intraperitoneal culturing during appendectomy is a routine procedure.
      Significant decrease in the mortality and dramatic improvement in the morbidity
      were achieved by using antibiotics perioperatively. The value of intraoperative
      abdominal cavity culture was assessed in our study. METHODS: A total of 499
      patients formed two groups, those with acute nonperforated appendicitis (group A)
      and those with perforated appendicitis (group B). Intraoperative abdominal cavity
      culture were taken randomly in both groups. The perioperative morbidity, the
      validity, and the impact of positive culture on the antibiotic treatment were
      examined in both groups. RESULTS: Clinical diagnosed perforation was confirmed
      histologically in 176 patients (98.3% accuracy). Intraperitoneal cultures were
      obtained in 30.1% of the patients in group A and in 67.1% of group B. The
      majority of the patients in group A were treated preoperatively and
      postoperatively by a single antibiotic agent whereas 58.0% of the patients in
      group B were started on triple-agent antibiotics for significantly longer periods
      (22.4 +/- 9.4 versus 5.7 +/- 7.4 doses, respectively; P < 0.0001). No significant
      difference was found in both groups in the postoperative complication rate (wound
      infection, intra-abdominal abscess and small bowel obstruction) whether intra
      abdominal culture was obtained or not (5.9% versus 4.7% in group A and 21.2%
      versus 21.9% in group B; P > 0.05). CONCLUSION: Traditional intraoperative
      abdominal cavity culture can be abandoned. In perforated appendicitis, colonic
      flora can be predicted, and antibiotic therapy should begun without any abdominal
      cavity culture results. This practical approach will save money and reduce
      laboratory work without affecting the patient's morbidity.

PMID- 9568650
TI  - Minimally invasive antireflux surgery.
AB  - BACKGROUND: Previous reports of minimally invasive antireflux surgery for
      gastroesophageal reflux disease (GERD) have been small, short-term series
      utilizing only a laparoscopic approach. We conducted a retrospective review and
      report our 66-month experience with more than 1,000 laparoscopic and
      thoracoscopic antireflux procedures. METHODS: Between September 1991 and October
      1997, 968 adults underwent 1,003 minimally invasive antireflux procedures on a
      tailored basis, based on their preoperative evaluation. Procedures performed were
      laparoscopic Nissen (626), Toupet (348), paraesophageal (33), and thoracoscopic
      Belsey (22). A total of 23% (233) of patients underwent an ancillary procedure
      (esophageal myotomy 85, vagotomy 67, pyloromyotomy 13, and cholecystectomy 66).
      RESULTS: Follow-up averaged 33 months (range 1 to 66), operative mortality was
      0.1%. Complications occurred in 2.7% with a 1% long-term dysphagia rate.
      Demonstrated recurrence rate was 3.8% to date, with an associated 3.4% reporting
      symptoms of GERD. CONCLUSION: Minimally invasive antireflux procedures provide
      sustained relief of GERD symptoms with low morbidity and rapid recovery.

PMID- 9568651
TI  - Clinical evaluation of nerve-sparing surgery combined with preoperative
      radiotherapy in advanced rectal cancer patients.
AB  - BACKGROUND: Since 1984, we have studied nerve-sparing surgery (NSS) combined with
      preoperative radiotherapy (XRT) in patients with advanced rectal cancer to
      preserve the genitourinary function without compromising radicality. The present
      aim was to evaluate the prognosis and the postoperative genitourinary function.
      METHODS: A total of 167 patients with advanced rectal cancer underwent curative
      nerve-sparing surgery. Among them, 60 underwent the preoperative therapy using
      irradiation (42.6 Gy) and tegafur suppository. Survival, local recurrence, and
      postoperative genitourinary function were investigated in these patients.
      RESULTS: The 5-year survival rate was 80.9% and the local recurrence rate was
      6.7% in the NSS+XRT group. Almost all of the patients receiving NSS could
      micturate spontaneously, but preservation of sexual function was not as
      successful. CONCLUSIONS: Better local control and preservation of urinary
      function were possible in advanced rectal cancer patients by NSS+XRT.

PMID- 9568652
TI  - Accuracy of computed tomography in determining resectability for locally advanced
      primary or recurrent colorectal cancers.
AB  - AIM: To determine the accuracy of computed axial tomography (CT) in determining
      tumor resectability in patients with locally advanced primary (T4) or locally
      recurrent colorectal cancer. METHODS: Computed tomography scans of 84 patients
      with "resectable" locally advanced primary rectal cancer (n = 12) or recurrent
      colorectal cancer (n = 72) were compared with the operative findings to assess
      the accuracy of abdominal and pelvic CT in determining extent of disease and
      resectability. RESULTS: At surgery, disease was confined to the pelvis in 63
      patients, the abdomen in 7, and involved both the pelvis and abdomen in 14.
      Computed tomography correctly identified these anatomic sites of tumor in 87% of
      patients, with 89% and 80% accuracies for pelvic and abdominal disease,
      respectively. Tumor resection was performed in 71 patients (85%), but was not in
      13 patients because of locally unresectable disease in 8 and metastatic disease
      in 5. The accuracy of predicting tumor-related operability was 85%. With regard
      to adjacent organ resection, CT was accurate in determining the need for
      sacrectomy or hysterectomy, but overestimated the need for urinary organ
      resection. Based on histological examination of resection margins, CT correctly
      staged (n = 45) or overstaged (n = 9) 54 patients (64%) and understaged the
      remaining 30. The ability of CT to preoperatively predict a locally advanced
      tumor after preoperative radiation therapy as not being fixed was 30%, fixed but
      resectable 75%, and fixed but not resectable 25%. CONCLUSIONS: Computed
      tomography is generally reliable at identifying disease as being confined to one
      region, and for predicting the need for adjacent organ resection. It is less
      discriminating for predicting local tumor resectability.

PMID- 9568653
TI  - Treatment of local recurrence of rectal cancer.
AB  - BACKGROUND: Treatment of local recurrence of rectal cancer remains a challenge.
      Preoperative irradiation and total mesorectal excision halve the risks of local
      failure, but increase morbidity and even mortality. The results of re-resection
      of recurrent rectal cancer suggest need to reexamine therapeutic strategies for
      initial treatment. METHODS: Seventy-one patients operated on for rectal carcinoma
      without radiotherapy developed local recurrence (29 with metastatic disease).
      Thirty underwent a curative re-resection (8 had combined resection of
      metastases). RESULTS: The incidence of asymptomatic recurrence was higher after
      anterior resection (38%) than after abdominoperineal resection (16%). The
      actuarial 5-year survival rate was 19%; 28% in asymptomatic patients and 8% in
      symptomatic (P = 0.04). CONCLUSIONS: Early detection of recurrence of rectal
      cancer leads to an improved re-resection rate and survival. In patients who did
      not undergo radiotherapy at the time of the original resection, re-resection can
      be achieved safely. The place for radiation in the treatment of rectal cancer
      must be redefined.

PMID- 9568654
TI  - The utility of hemodynamic measurements acquired by pulmonary artery
      catheterization.
AB  - BACKGROUND: Concerns about the utility of pulmonary artery catheters (PAC)
      stimulated us to assess the impact of one of the parameters measured by the PAC,
      the pulmonary capillary wedge pressure (PCWP), on our clinical practice. METHODS:
      The PCWP was recorded at 4- to 6-hour intervals on 50 patients for the first 48
      hours following aortic aneurysm repair. We then reviewed the patients' records
      looking for evidence that the PCWP measurements were used to guide therapy. For
      the purpose of the study, we anticipated the administration of diuretics for PCWP
      > or =218 mm Hg and volume resuscitation for PCWP < or =8 mm Hg. Data were
      correlated using Pearson rank correlation coefficient using a P < 0.05 to
      determine statistical significance. RESULTS: Patients with PCWPs <8 mm Hg were
      more likely to be treated with volume resuscitation (P < 0.05). There was no
      other correlation between PCWP measurements and fluid or pharmacologic
      management. CONCLUSIONS: Data derived from the PAC are infrequently used to guide
      therapy in patients who undergo abdominal aortic reconstructive surgery.

PMID- 9568656
TI  - Parathyroidectomy in patients with chronic renal failure.
AB  - BACKGROUND: Hyperparathyroidism is common in patients with renal disease. These
      patients may require operation for this disease if it cannot be controlled by
      medical therapy. Because these patients continue to have renal failure, the risk
      of recurrence and reoperation is high. METHODS: Sixty-nine patients with renal
      failure underwent operation for hyperparathyroidism. These patients were followed
      up on dialysis or after transplantation. RESULTS: Sixty-nine patients, aged 2 to
      71 years old, with end-stage renal disease required parathyroidectomy for
      hyperparathyroidism 6.2 +/- 4.2 (standard deviation) years after beginning
      dialysis. Thirty-six patients had undergone renal transplantation (creatinine =
      1.6 +/- 0.4 mg/dL). All patients had elevated parathyroid hormone (PTH) levels.
      Sixty-eight patients had hyperplasia; 1 patient had adenoma. Six patients
      required reoperation for recurrent hyperparathyroidism 30 to 123 months after
      their initial parathyroidectomy. CONCLUSION: Patients with end-stage renal
      disease are prone to abnormalities of calcium metabolism. They frequently develop
      parathyroid hyperplasia. Recurrence can occur following operation because of
      continuing renal failure.

PMID- 9568655
TI  - An activated state of blood coagulation and fibrinolysis in patients with
      abdominal aortic aneurysm.
AB  - BACKGROUND: Relationships between blood coagulation and the fibrinolysis system
      and morphology of aneurysms in patients with abdominal aortic aneurysm (AAA) are
      unknown. METHODS: Preoperative and postoperative evaluations of hemostatic
      factors such as thrombin-antithrombin III complex (TAT), D-dimer,
      fibrinogen/fibrin degradation products (FDP), and platelet count were performed
      in 36 patients with atherosclerotic AAA. As control subjects, 25 age- and sex
      matched healthy volunteers were analyzed for these hemostatic factors. In all
      patients, morphological evaluation of AAA included the largest diameter,
      tortuosity, and the thickness of intraluminal thrombus to be compared with
      preoperative levels of hemostatic factors such as alpha-2 plasmin inhibitor
      plasmin complex (PIC), thrombomodulin (TM), von Willebrand factor (vWF), tissue
      factor (TF), and free form of tissue factor pathway inhibitor (F-TFPI). RESULTS:
      The preoperative values of TAT, D-dimer, and FDP were significantly higher in AAA
      patients than in controls. Of all patients, 23 (64%) or 22 (58%) had TAT or D
      dimer values greater than 8.2 ng/mL or 3.4 microg/mL (mean + 2SD of controls),
      respectively. The postoperative values of these hemostatic factors significantly
      improved, but were not normalized. The largest diameter of AAA correlated with
      the preoperative levels of TAT (r = 0.566, P = 0.001), D-dimer (r = 0.644, P =
      0.0001), FDP (r = 0.561, P = 0.0009), PIC (r = 0.413, P = 0.0146), and F-TFPI (r
      = 0.408, P = 0.0158). We have also found that tortuosity of AAA has relation not
      only to the preoperative levels of fibrinolytic factors but also to the plasma F
      TFPI antigen levels. On the other hand, the preoperative levels of a marker of
      endothelial damage, such as TM or vWF, and TF did not correlate with those of F
      TFPI in all patients. The maximum thickness of thrombus in AAA significantly
      correlated not only with the preoperative levels of TAT, D-dimer, FDP, and PIC,
      but also with AAA size. CONCLUSIONS: We have found evidence that an activated
      state of both blood coagulation and fibrinolysis in AAA patients is associated
      with the morphological characteristics of aneurysms.

PMID- 9568657
TI  - Surgical strategy for insulinomas in multiple endocrine neoplasia type I.
AB  - BACKGROUND: Hyperinsulinemia in multiple endocrine neoplasia type I (MEN-I) is a
      rare but potentially curable condition that presents difficulties not encountered
      in sporadic cases. METHODS: The present report documents our surgical approach to
      3 MEN-I patients with hyperinsulinemia. RESULTS: Primary hyperparathyroidism was
      manifested in all 3 patients at the time of presentation. Distal subtotal
      pancreatectomy with enucleation of tumor at the head of pancreas detected
      intraoperatively resulted in immediate cure of 2 patients. Persistent disease
      occurred in 1 patient after enucleation of tumor at the head of the pancreas
      guided by preoperative imaging elsewhere. The patient was subsequently cured by
      distal subtotal pancreatectomy. Pathology revealed multiple tumors (4 to 14) in
      all patients. CONCLUSIONS: A different surgical strategy with an aim of distal
      subtotal pancreatectomy and enucleation of any tumor identified in the head of
      pancreas is the treatment of choice for hyperinsulinemia in MEN-I patients.

PMID- 9568658
TI  - Can Ringer's lactate be used safely with blood transfusions?
AB  - BACKGROUND: Blood bank recommendations specify that Ringer's lactate solution
      (LR) should be avoided while transfusing blood. However, there are few studies
      either evaluating or quantifying increased coagulation during rapid infusion of
      LR and blood. DESIGN AND METHODS: Whole blood (WB, n = 25) and packed red blood
      cells (PRBC, n = 26) were rapidly admixed with normal saline (NS), Lactate
      solution and LR with 1 g (LR-1), 2 g (LR-2), and 5 g (LR-5) CaCl2/L solutions for
      assessment of infusion time, filter weight, and clot formation. RESULTS: No
      significant differences in infusion time or filter weight using WB or PRBC with
      NS or LR were seen. No significant difference in clot formation between NS and LR
      with WB or PRBC was found, but the presence of visible clot was increased in the
      LR-5 group (P = 0.013, WB, and P = 0.002, PRBC). CONCLUSION: A comparison of LR
      and NS with rapid infusion rates of blood showed no significant difference
      between infusion time, filter weight and clot formation. Blood bank guidelines
      should be revised to allow the use of LR in the rapid transfusion of PRBC.

PMID- 9568660
TI  - Prophylactic cholecystectomy is not indicated following renal transplantation.
AB  - BACKGROUND: The appropriate management of gallstones in patients undergoing renal
      transplantation is controversial. Screening for gallstones and subsequent
      prophylactic cholecystectomy has been recommended by some authors for kidney
      transplant candidates. Our program does not practice routine pretransplant
      screening for gallstones, and we reviewed our data to determine the outcome of
      our management approach. METHODS: We reviewed the records of the 1,364 currently
      followed patients who have undergone kidney transplant at our institution since
      1985 in order to evaluate the morbidity and mortality of biliary disease in the
      post-transplant period. We attempted to contact all patients by telephone or mail
      survey for the presence of biliary tract disease or operations. RESULTS: Six
      hundred and sixty-two patients were fully evaluated. Fifty-two (7.85%) required
      cholecystectomy for stone disease. Seven patients underwent incidental
      cholecystectomy during other operations, 2 patients developed acalculus
      cholecystitis, and 14 patients with asymptomatic cholelithiasis are being
      followed up. Surgical indications included 38 biliary colic, 9 acute
      cholcystitis, 3 gallstone pancreatitis, and 2 patients who were asymptomatic.
      Fifty-two patients underwent 30 laparoscopic cholecystectomies, 20 open
      cholecystectomies, and 2 conversions. Surgery occurred from 7 days to 9.6 years
      following transplantation. Overall, the median hospital stay (no postoperative
      stay) was 4 days (range 1 to 57). Patients undergoing laparoscopy had a median
      stay of 2 days compared with 7 days for those undergoing an open procedure.
      Complications were seen in 6 patients (11.5%) with no morbidity and no graft
      loss. The 1-, 2-, and 5-year graft survival was 98%, 96%, and 85%, respectively,
      in patients undergoing cholecystectomy. CONCLUSIONS: Transplant patients are not
      at an increased risk for developing biliary tract disease compared with
      nontransplant patients. Gallstone disease does not have a negative impact on
      graft survival. Treatment of gallstones has a low risk and does not represent an
      increased risk of complications in patients following renal transplantation.

PMID- 9568659
TI  - Peritoneal cytokine release after elective gastrointestinal surgery and
      postoperative complications.
AB  - BACKGROUND: Laparotomy is known to give rise to systemic and local cytokine
      release. In the present study we investigated the course of the peritoneal
      response of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, and IL-10
      after elective gastrointestinal surgery and studied the differences in local
      cytokine response in patients developing postoperative complications. METHODS:
      Twelve consecutive patients underwent pancreatoduodenectomy (n = 9) or biliary
      and gastric bypass (n = 3) for pancreatic carcinoma. Sampling (TNFalpha, IL-6, IL
      10) of fluid from abdominal drains was performed at return to the recovery unit
      (T=0), and at 3, 6, 18, 30, 42, 54, 66, 78 hours. Systemic sampling was performed
      at T=0, 3, 6, 18, 42, 66 hours. Postoperative cytokine response in patients with
      and without postoperative complications was compared. RESULTS: In patients
      without postoperative complications, peritoneal TNFalpha and IL-10 levels
      decreased in time (P = 0.07 and P = 0.01, respectively), whereas IL-6 did not
      change significantly during sampling (P = 0.28). Systemic IL-6 and IL-10 levels
      decreased 10-fold within 66 hours (IL-6, P = 0.04; IL-10, P = 0.06). Four
      patients experienced postoperative complications. All 4 patients with
      complications showed a second rise in peritoneal TNFalpha levels preceding the
      complication. All 4 patients had positive bacterial drain cultures from the
      abdominal drain, following the TNFalpha rise. CONCLUSIONS: After elective
      abdominal surgery, cytokines are released into the abdominal cavity. Intra
      abdominal complications are accompanied or preceded by a peritoneal TNFalpha
      rise. In patients after elective gastrointestinal surgery, monitoring of
      peritoneal TNFalpha might be helpful in the early detection of severe intra
      abdominal complications.

PMID- 9568661
TI  - Biliary surgery after heart transplantation.
AB  - BACKGROUND: Biliary tract diseases are frequent in heart transplant recipients,
      with significant morbidity and mortality. Since the first presentation of
      gallstones in this population is often acute cholecystitis, asymptomatic
      cholelithiasis should not be considered benign. PATIENTS AND METHODS: We
      retrospectively reviewed 18 heart transplant recipients who underwent
      cholecystectomy from January 1991 to June 1997. We intentionally chose to perform
      a straightforward open procedure when acute cholecystitis was suspected (3
      patients). A laparoscopic cholecystectomy was performed in all the other cases
      (15 patients) without conversion to open procedure. CONCLUSION: Since no
      significant complications were observed in our patients, we believe that
      transplant recipients with cholelithiasis should undergo laparoscopic
      cholecystectomy in their posttransplantation course regardless of the symptomatic
      status of their biliary tract.

PMID- 9568662
TI  - Sequential percutaneous microwave coagulation therapy for liver tumor.
AB  - BACKGROUND: Percutaneous microwave coagulation therapy (PMCT) is effective for
      small liver tumors. To enhance the radicality of PMCT, we developed a sequential
      coagulation technique. METHODS: After inserting the first guide-needle under
      sonography, multiple needles were placed through a disk-type introducer that was
      devised to guide needle puncture at regular intervals, and microwaves were
      irradiated. Six patients, including 4 with hepatocellular carcinoma and 2 with
      liver metastasis, underwent this technique for tumors of 15 to 80 mm in diameter.
      RESULTS: This technique can coagulate an area up to 60 mm in diameter in one
      session. Insertion of multiple needles, ranging from 2 to 11, was successful
      without complications. Three patients undergoing curative PMCT developed no tumor
      recurrence. The other 3 received incomplete PMCT due to the large size and
      location of the tumor. CONCLUSIONS: This preliminary study indicates the efficacy
      of this technique to facilitate and secure PMCT in selected patients with liver
      tumors.

PMID- 9568663
TI  - A randomized comparison of acute phase response and endotoxemia in patients with
      perforated peptic ulcers receiving laparoscopic or open patch repair.
AB  - BACKGROUND: In patients with peritonitis from perforated peptic ulcers, we
      compared acute stress responses, endotoxemia, and bacteremia following
      laparoscopic or open surgery. PATIENTS AND METHODS: Consecutive patients with
      peritonitis from perforated peptic ulcers were randomized to receive laparoscopic
      sutured or open omental repair. Undiluted peritoneal fluid was obtained at
      surgery for quantitative bacterial and endotoxin (Limulus Amoebocyte Lysate)
      assay. Serial blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes,
      and at 12, 24, 48, 72, and 120 hours for determinations of quantitative bacterial
      and endotoxin assays, interleukin-6 (IL-6), C-reactive protein (CRP), and
      cortisol. RESULTS: Twenty-two patients were randomized: laparoscopy group (n =
      12), open repair group (n = 10). Conversions were required in 3 patients assigned
      to laparoscopy, leaving 9 patients for analysis. The two groups were comparable
      in their demographic data, median duration of perforation (13.5 hours versus 10
      hours), severity of peritoneal contamination as indicated by viable bacterial
      count (5.9 x 102 versus 1.5 x 10(2) colony forming unit/mL) and endotoxin
      concentration in peritoneal fluid (27.2 versus 24.6 EU/mL). No significant
      endotoxemia or bacteremia was detected in these patients. Median interleukin-6
      was highest at 0 hour (1520 versus 962 pg/mL) and fell rapidly following surgery.
      C-reactive protein peaked at 24 hours and plateaued thereafter. Cortisol was
      highest intraoperatively and fell thereafter. No difference was noted between the
      two treatment groups with respect to these inflammatory markers (IL-6 P = 0.19,
      CRP P = 0.14, cortisol P = 0.56, multivariate analysis of variance). CONCLUSION:
      Endotoxemia and bacteremia are insignificant in most patients with perforated
      peptic ulcers. In patients with perforated peptic ulcers, laparoscopic patch
      repair does not reduce acute stress responses when compared with open surgery.

PMID- 9568664
TI  - A technique for pancreaticogastrostomy.
AB  - A technique for pancreaticogastrostomy is presented. The technique is a one
      layer, invaginated anastomosis of the pancreatic remnant to the posterior gastric
      wall following a Whipple resection of the pancreatic head. Key steps to achieve a
      successful anastomosis are described. Using this technique, there have been no
      pancreatic anastomotic leaks in 29 consecutive patients.

PMID- 9568665
TI  - Prospective randomized study comparing laparoscopic and open tension-free
      inguinal hernia repair with Shouldice's operation.
AB  - BACKGROUND: Although tension-free techniques of hernia repair using synthetic
      meshes revealed encouraging results, the best method of inguinal hernia repair is
      still unclear. METHODS: In a prospective randomized phase-II-B study, early
      postoperative results of laparoscopic transabdominal preperitoneal repair (n =
      80), open plug and patch repair (n = 80), and Shouldice's operation (n = 80) were
      compared. Postoperative pain and patient's comfort were defined as main
      endpoints. RESULTS: The laparoscopic approach had significantly longer operation
      time and was more expensive (61 +/- 12 minutes; $1,211) than plug and patch
      repair (36 +/- 14 minutes; $124) and Shouldice's operation (47 +/- 17 minutes;
      $69). Main postoperative complications were wound hematomas, seromas, and
      superficial wound infection, without significant difference between the groups.
      Postoperative pain, analgesia requirements, limitation of daily activities, and
      return to work did not differ between laparoscopic and open tension-free repair
      but were significantly lower in both groups compared with Shouldice's operation.
      So far, no recurrence was observed after a mean follow-up of 25 months.
      CONCLUSION: Open plug and patch repair is a promising technique of hernia repair
      in adults, because it offers the same excellent patient comfort as the
      laparoscopic repair but is less expensive and can be performed under local
      anesthesia.

PMID- 9568666
TI  - Trapidil effects on intimal thickening and mRNA levels for platelet-derived
      growth factor A in human saphenous vein smooth muscle cells.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF) A chain, basic fibroblast
      growth factor (bFGF), and tissue-type plasminogen activator (tPA) from smooth
      muscle cells (SMCs) have been postulated to initiate SMC proliferation and
      migration in the process of intimal thickening. OBJECTIVE: In this study we
      tested whether trapidil, which is reported to reduce intimal thickening, would
      suppress mRNA increases for all or only some of these genes in human SMC.
      METHODS: Cultured human saphenous vein SMCs made quiescent by 72-hour incubation
      in 0.5% serum were stimulated with 3U/mL alpha-thrombin +/- trapidil. Changes in
      mRNA transcript levels were analyzed by Northern blot. RESULTS: Trapidil
      decreased thrombin-induced mRNA levels for bFGF and appeared to decrease mRNA for
      PDGF-A chain, but not for tPA. CONCLUSION: These results suggest that trapidil
      may reduce intimal thickening at least partly via the suppression of increased
      bFGF and PDGF-A chain mRNA levels in vascular SMCs.

PMID- 9568667
TI  - Comparison of stapled and hand-sewn esophagogastric anastomoses.
AB  - BACKGROUND: Esophagogastric anastomotic leaks continue to be a major source of
      morbidity and mortality after esophagectomy. Leaks usually result from technical
      errors or occult ischemia of the mobilized gastric fundus. The introduction of
      stapled esophagogastric anastomoses was initially very promising; leak rates
      appeared to be reduced. DATA SOURCES: The English language medical literature was
      searched for publications comparing stapled and hand-sewn esophagogastric
      anastomoses. We reviewed data from four randomized trials and seven nonrandomized
      comparative studies to determine if stapling was superior to hand suturing for
      esophagogastric anastomoses. RESULTS: Pooled data from randomized trials
      comparing stapled with hand-sewn esophagogastric anastomoses showed no
      significant difference for leaks (stapled 9%, hand-sewn 8%, P <0.67), but a
      higher incidence of strictures in stapled anastomoses (stapled 27%, hand-sewn
      16%, P < 0.02). In nonrandomized studies, stapled anastomoses had a lower leak
      rate (stapled 6%, hand-sewn 11%, P < 0.0001), but strictures were more frequent
      (stapled 31%, hand-sewn 16%, P < 0.0001). A major source of bias in the
      nonrandomized studies was the comparison of contemporary stapled experience and
      earlier hand-sewn experience. This bias was not present in three of seven
      nonrandomized studies that featured prospective data collection. Pooled data from
      these three studies showed no difference in anastomotic leak rate (stapled 4%,
      hand-sewn 6%, P < 0.28). CONCLUSIONS: Stapled and hand-sewn esophagogastric
      anastomotic techniques have equivalent anastomotic leak rates, but strictures are
      more common in stapled anastomoses. Irrespective of which technique is used,
      surgical experience and meticulous attention to detail are required to prevent
      anastomotic complications. Anastomotic technical modifications alone are unlikely
      to eliminate the problem of leaks, since they do not address the problem of
      gastric fundal ischemia.

PMID- 9568668
TI  - Early versus late necrosectomy in severe necrotizing pancreatitis.

PMID- 9568669
TI  - Usefulness of ultrasonography for detecting inguinal disorders.

PMID- 9568670
TI  - Expanded polytetrafluoro-ethylene patches.

PMID- 9568671
TI  - Osteopontin stimulates a subpopulation of quiescent human prostate epithelial
      cells with high proliferative potential to divide in vitro.
AB  - BACKGROUND: Osteopontin (OPN) is a secreted extracellular matrix (ECM) protein
      found in bone, as well as associated with epithelial cells. The main objective of
      these studies was to test in vitro the hypothesis that interaction with OPN
      stimulates proliferation of a quiescent subpopulation of prostate epithelial
      cells with high proliferative potential. METHODS: To simulate conditions that
      restrict proliferation and inhibit terminal differentiation of basal cells in
      vivo, control cultures grew on substrate coated with collagen (CO) or fibronectin
      (FN), in medium containing low levels of growth factors. RESULTS: Under growth
      restricting conditions, most prostate epithelial cells with high proliferative
      potential, seeded in control secondary cultures, were quiescent within the time
      frame of the studies, as indicated by the small number of large colonies in these
      cultures. Growing prostate epithelial cells (PR) under the same growth
      restricting conditions, but on substrate coated with OPN instead of CO or FN,
      stimulated proliferation of a subpopulation of single cells with high
      proliferative ability as indicated by: 1) dose-dependent increase in the
      percentage of single cells incorporating bromodeoxyuridine, i.e., proliferating
      PR; and 2) subsequent dose-dependent increase in the percentage of large
      colonies. The OPN effect was not merely due to preferential attachment to OPN,
      because PR attachment to OPN, CO, or FN was identical. PR attachment to OPN was
      inhibited in the presence of GRGDTP or an antibody against the integrin subunit
      alphav, but not in the presence of an RGES peptide or a nonspecific IgG.
      CONCLUSIONS: Integrin-mediated OPN/PR interaction stimulates proliferation of a
      quiescent subpopulation of prostate epithelial cells with high proliferative
      potential, possibly stem cells.

PMID- 9568673
TI  - Testosterone-induced prostatic growth in the rat causes bladder overactivity
      unrelated to detrusor hypertrophy.
AB  - BACKGROUND: Testosterone treatment of rats produces prostatic hypertrophy and
      detrusor overactivity. Whether or not the detrusor overactivity can be related to
      an increase in the responsiveness of lower urinary tract smooth muscles is not
      known. METHODS: Male Sprague-Dawley rats were given daily injections of
      testosterone propionate for 2 weeks. Effects on cystometric parameters and on the
      responsiveness of isolated detrusor, urethral, and prostate smooth muscle
      preparations to drugs and electrical field stimulation were investigated.
      RESULTS: Testosterone treatment increased prostatic weight twofold (controls, 768
      mg; testosterone-treated, 1,478 mg), but not bladder weight (103 mg vs. 116 mg).
      Micturition pressure (77%), bladder capacity (75%), residual volume (56%), and
      micturition volume (83%) increased significantly in treated animals, and bladder
      overactivity developed. No effect of intraarterial doxazosin on these changes was
      observed. The differences in urodynamic parameters between control and
      testosterone-treated rats could not be correlated with changes in bladder,
      urethral, or prostate excitatory innervation, as revealed by responses to
      electrical field stimulation, or by smooth muscle responses to different
      contractant drugs. CONCLUSIONS: Some of the urodynamic effects seen after
      testosterone treatment seem to be caused by the mechanical obstruction of the
      enlarged prostate. Since there were no changes in smooth muscle responsiveness,
      it is suggested that the bladder overactivity observed can partly be related to
      testosterone-induced changes of the micturition reflex at the lower urinary
      tract, spinal, and/or supraspinal levels.

PMID- 9568672
TI  - Cyclin D1 expression in human prostate carcinoma cell lines and primary tumors.
AB  - BACKGROUND: The cyclin D1 gene is amplified and/or overexpressed in several types
      of human cancer, including cancers of the breast, esophagus, head, and neck.
      However, the role of cyclin D1 in prostate cancer has not been previously studied
      in detail. METHODS: Six human prostate cancer cell lines and cultures of normal
      human prostate cells were examined by Western and Northern blot analyses for
      levels of expression of the cyclin D1 protein and mRNA, respectively. Southern
      blot analyses were performed to examine possible amplification of this gene.
      Immunostaining for cyclin D1 was performed on 50 primary prostate cancer samples.
      RESULTS: Cyclin D1 protein was expressed at relatively high levels in all of the
      six human prostate cancer cell lines examined, but was not detected in the
      cultures of normal human prostate cells. The ALVA 41 cell line expressed the
      highest level of this protein. Relatively high levels of cyclin D1 mRNA were also
      found in all of the prostate cancer cell lines. Nevertheless, none of these cell
      lines revealed amplification of the cyclin D1 gene. Twelve of the 50 primary
      prostate cancer samples (24%) revealed regions of moderate to strongly positive
      staining for cyclin D1. CONCLUSIONS: The increased expression of cyclin D1 in
      several prostate cancer cell lines and in a subset of primary prostate cancer
      samples suggests that further studies on the expression of this gene and related
      genes may be of interest in understanding the pathogenesis of prostate cancer.

PMID- 9568674
TI  - Cellular expression of beta-microseminoprotein (beta-MSP) mRNA and its protein in
      untreated prostate cancer.
AB  - BACKGROUND: Previous studies have shown that beta-microseminoprotein (beta-MSP)
      may be used as a diagnostic marker for prostate cancer. However, the level of
      expression of beta-MSP in prostate cancer detected by immunohistochemistry (IHC)
      has varied from one study to another. METHODS: We analyzed the expression of both
      beta-MSP mRNA and its protein in a large sample of prostate tumors from 104
      patients with untreated prostate cancer, using both nonradioactive in situ
      hybridization (ISH) and IHC. RESULTS: Our results showed that 72 and 96 of 104
      specimens were negative for beta-MSP mRNA (69.2%) and beta-MSP (92.3%),
      respectively. Furthermore, a reduced expression of both beta-MSP mRNA and its
      protein was detected in all malignant epithelial tissues compared with benign
      epithelia. Not all malignant tissue samples negative for beta-MSP mRNA were
      negative for beta-MSP (6.7%), and vice versa (29.8%). Other tissue samples were
      either negative for both (62.5%) or positive for both (1.0%). CONCLUSIONS: Our
      results showed a lower level of expression of beta-MSP in prostate cancer tissue,
      compared with benign prostate tissue. This phenomenon may be mainly due to the
      presence of reduced levels of beta-MSP mRNA.

PMID- 9568675
TI  - Epidermal growth factor induces cyclin D1 in a human prostate cancer cell line.
AB  - BACKGROUND: The human prostate carcinoma cell line, LNCaP, proliferates under
      stimulation by a limited number of mitogenic signals, which include members of
      the growth factor and steroid hormone families. Androgens and epidermal growth
      factor (EGF) are among the LNCaP cell mitogens. We tested the hypothesis that
      these mitogens stimulate LNCaP cell proliferation at least in part through the
      induction of cyclin D1, a protein requisite for cell cycle progression, which is
      expressed in the G1 phase of the cell cycle. METHODS: LNCaP cells were grown in
      serum-free medium with 10 ng/ml or 100 ng/ml EGF, 0.1 nM or 1.0 nM mibolerone (a
      potent androgen agonist), or vehicle (distilled water or 0.01% ethanol).
      Expression of cyclin D, mRNA, and protein were assessed by Northern and Western
      blot analyses. Transcription regulation was assessed by nuclear runoff assay.
      RESULTS: Western analyses demonstrated that EGF stimulated cyclin D1 protein
      expression 4-fold over 12 hr. Northern analyses showed a 4-fold increase in mRNA
      expression, peaking within 4 hr of EGF stimulation. There were no effects on
      cyclin D1 protein or mRNA expression with mibolerone treatments. We further
      explored the mechanism of cyclin D1 induction. LNCaP cells stimulated for 1 hr
      with EGF demonstrated a 2-fold increase in cyclin D1 message, as assayed by
      nuclear runoff transcription assay. In addition, we demonstrated the involvement
      of the protein kinase C pathway in mediating the EGF induction of cyclin D1.
      CONCLUSIONS: We conclude that one of the mechanisms by which growth factors such
      as EGF may stimulate prostate cell proliferation is through the direct induction
      of cyclin proteins, which are necessary for entry of cells into mitosis.

PMID- 9568676
TI  - Basic FGF, EGF, and PDGF modify TGFbeta-induction of smooth muscle cell phenotype
      in human prostatic stromal cells.
AB  - BACKGROUND: We investigated the ability of a variety of growth factors to
      regulate the differentiation of prostatic fibroblasts into smooth muscle cells.
      METHODS: Smooth muscle actin levels were monitored by immunoblot analysis and
      immunocytochemistry. Proliferation was measured in clonal growth assays and by
      cell counts. RESULTS: We determined that TGFbeta inhibited proliferation and
      induced smooth muscle differentiation of stromal cells derived from prostatic
      adenocarcinomas, as we previously reported for cells derived from the normal
      peripheral zone. Basic FGF, EGF, TGFalpha, and PDGF, but not IGF, retinoic acid,
      1,25-dihydroxyvitamin D3, or androgen, attenuated induction of differentiation by
      TGFbeta, by a mechanism apparently unrelated to proliferation. CONCLUSIONS:
      Regulation of growth and differentiation occurs equivalently in prostatic stromal
      cells derived from adenocarcinomas and normal peripheral zone. TGFbeta is a
      potent inducer of the smooth muscle phenotype. Basic FGF, EGF and/or TGFalpha,
      and PDGF attenuate TGFbeta's activity, and promote a fibroblastic phenotype. Our
      studies provide an in vitro model system in which fibroblastic or smooth muscle
      cells can be promoted, maintained, and investigated in a defined manner. The
      results suggest that the ratio of fibroblasts to smooth muscle cells in the
      stroma reflects the relative levels of growth factors, which may be altered in
      diseased states.

PMID- 9568677
TI  - LNCaP produces both putative zymogen and inactive, free form of prostate-specific
      antigen.
AB  - BACKGROUND: Our objective was to investigate the presence of prostate specific
      antigen (PSA) and alpha-1-antichymotrypsin (ACT) mRNA and protein in prostate
      cancer cell lines, and the complexing characteristics of expressed PSA. METHODS:
      RT-PCR, immunohistochemistry, and Western blots were employed. Trypsin treatment
      of PSA was performed to establish the possible presence of an activatable form of
      PSA. RESULTS: ACT mRNA and protein were detected in LNCaP, PC-3, and DU 145 by RT
      PCR and by immunohistochemistry, respectively. Only LNCaP cells were positive for
      PSA mRNA and protein. LNCaP expressed approximately 30% active PSA, approximately
      40% putative zymogen form of PSA, and approximately 30% stably inactive PSA.
      CONCLUSIONS: We have shown that the majority of PSA expressed by LNCaP cells is
      present in free, noncomplexed forms in the conditioned media. A portion (40%) can
      be activated by trypsin, while the rest is stably inactive PSA. LNCaP cells may
      serve as a source of the "unreactive" PSA present in prostate cancer patients'
      serum.

PMID- 9568678
TI  - Report of immune monitoring of prostate cancer patients undergoing T-cell therapy
      using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific
      membrane antigen (PSMA).
AB  - BACKGROUND: In this paper we describe our program for the immune monitoring of
      phase II participants given dendritic cell (DC)/prostate-specific membrane
      antigen (PSMA)-based immunotherapy, and we also present some initial findings.
      METHODS: Phase II subjects received six administrations of autologous dendritic
      cells exogenously pulsed with two peptides derived from PSMA. Prior to the
      initial infusion, and following each treatment, peripheral blood mononuclear
      cells (PBMC) were collected for the generation of dendritic cells as well as for
      comprehensive immune monitoring. RESULTS: Thus far, an increase in PSMA-peptide
      specific as well as overall cellular reactivity has been observed in several
      patients receiving DC plus PSM-P1 and -P2, as measured by delayed-type
      hypersensitivity (DTH) test and enzyme-linked immunosorbant assay (ELISA).
      CONCLUSIONS: Our initial observations using an ELISA and DTH test indicate that
      we are enhancing cellular immunity in prostate cancer patients following infusion
      with DC plus PSMA-derived peptides. Several methods are underway to
      comprehensively monitor both cell-mediated and humoral immune responsiveness,
      including: determining anti-PSMA serum antibody titers, testing immunogen
      restricted responder-cell proliferation and cytotoxicity, assessing aberrations
      in signal transduction, antigen processing, and presentation, and measuring
      soluble factors that may promote tumor outgrowth.

PMID- 9568679
TI  - Does doxazosin affect prostatic growth?

PMID- 9568680
TI  - PPAR-gamma: adipogenic regulator and thiazolidinedione receptor.
AB  - The past several years have seen an explosive increase in our understanding of
      the transcriptional basis of adipose cell differentiation. In particular, a key
      role has been illustrated for PPAR-gamma, a member of the nuclear hormone
      receptor superfamily. PPAR-gamma has also been recently identified as the major
      functional receptor for the thiazolidinedione class of insulin-sensitizing drugs.
      This review examines the evidence that has implicated this transcription factor
      in the processes of adipogenesis and systemic insulin action. In addition,
      several models are discussed that may explain how a single protein can be
      involved in these related but distinct physiological actions. I also point out
      several important areas where our knowledge is incomplete and more research is
      needed. Finally, I discuss how advances in our understanding of nuclear receptor
      function, particularly the docking of cofactors in a ligand-dependent fashion,
      should lead to improved drugs that utilize the PPAR-gamma system for the
      treatment of insulin resistance.

PMID- 9568681
TI  - Tumor necrosis factor-alpha acutely inhibits insulin signaling in human
      adipocytes: implication of the p80 tumor necrosis factor receptor.
AB  - Tumor necrosis factor (TNF)-alpha is postulated to play a major role in the
      pathogenesis of obesity-linked insulin resistance, probably resulting from an
      interaction with insulin signaling pathways. This cross talk has now been
      investigated in human adipocytes at the level of phosphatidylinositol (PI) 3
      kinase, and the TNF receptors (TNFRs) mediating these processes have been
      identified. Equilibrium binding studies using human adipocytes from mammary
      tissue indicated the presence of two populations of TNFR with apparent affinity
      constants of 13 pmol/l and 1.6 nmol/l, respectively. Interaction of TNF-alpha
      with insulin signaling was determined by quantification of insulin receptor
      substrate (IRS)-1-associated PI 3-kinase activity. Under control conditions, PI 3
      kinase was activated about 10-fold in response to insulin (10[-7] mol/l, 5 min).
      Preincubation of adipocytes with 5 nmol/l TNF-alpha for 15 min resulted in a 60
      70% reduction of insulin action, reaching a stable inhibition (40%) after longer
      incubation with the cytokine. The inhibitory action of TNF-alpha was dose
      dependent, already detectable at 10 pmol/l, and was correlated to inhibition of
      tyrosine phosphorylation of IRS-1 with an unaltered autophosphorylation of the
      insulin receptor beta-subunit. The modulation of insulin signaling by TNF-alpha
      was found to be paralleled by a comparable inhibition of insulin-stimulated
      glucose transport. An agonistic TNFR1 antibody completely mimicked the inhibitory
      action of TNF-alpha on insulin signaling, whereas at 100 pmol/l TNF-alpha, a
      nonagonistic p80 TNFR antibody, was shown to ameliorate the inhibitory action of
      the cytokine. These findings indicate that in human adipocytes, low
      concentrations of TNF-alpha induce a rapid inhibition of insulin signaling at the
      level of PI 3-kinase. We suggest that under these conditions, the p80 TNFR is
      essential for initiating the intracellular cross talk that involves signaling by
      the p60 TNFR.

PMID- 9568682
TI  - Basal hepatic glucose production is regulated by the portal vein insulin
      concentration.
AB  - The ability of portal vein insulin to control hepatic glucose production (HGP) is
      debated. The aim of the present study was to determine, therefore, if the liver
      can respond to a selective decrease in portal vein insulin. Isotopic
      ([3H]glucose) and arteriovenous difference methods were used to measure HGP in
      conscious overnight fasted dogs. A pancreatic clamp (somatostatin plus basal
      portal insulin and glucagon) was used to control the endocrine pancreas. A 40-min
      control period was followed by a 180-min test period. During the latter, the
      portal vein insulin level was selectively decreased while the arterial insulin
      level was not changed. This was accomplished by stopping the portal insulin
      infusion and giving insulin peripherally at half the basal portal rate (PID,
      n=5). In a control group (n=5), the portal insulin infusion was not changed and
      glucose was infused to match the hyperglycemia that occurred in the PID group. A
      selective decrease of 120 pmol/l in portal vein insulin was achieved (basal,
      150+/-36 to last 30 min, 30+/-12 pmol/l) in the absence of a change in the
      arterial insulin level (basal, 30+/-3 to last 30 min, 36+/-4 pmol/l). Neither
      arterial nor portal insulin levels changed in the control group (30+/-6 and 126+/
      30 pmol/l, respectively). In response to the selective decrease in portal vein
      insulin, net hepatic glucose output (NHGO) increased significantly, from 8+/-1
      (basal) to 30+/-6 and 14+/-2 micromol x kg(-1) x min(-1) by 15 min and the last
      30 min (P < 0.05) of the experimental period, respectively. Arterial plasma
      glucose increased from 5.9+/-0.2 (basal) to 10.5+/-0.4 micromol/l (last 30 min).
      Three-carbon gluconeogenic precursor uptake fell from 11.2+/-2.9 (basal) to 5.9+/
      0.7 micromol x kg(-1) x min(-1) (last 30 min), and thus a change in
      gluconeogenesis could not account for any of the increase in NHGO. With matched
      hyperglycemia (basal, 5.5+/-0.3 to last 30 min, 10.5+/-0.8 micromol/l) but no
      change in insulin, NHGO decreased from 12+/-1 (basal) to 0 (-1+/-6 micromol x kg(
      1) x min(-1), last 30 min, P < 0.05) and hepatic gluconeogenic precursor uptake
      did not change (basal, 8.0+/-1.7 to last 30 min, 8.9+/-2.2 micromol x kg[-1] x
      min[-1]). Thus, the liver responds rapidly to a selective decrease in portal vein
      insulin by markedly increasing HGP as a result of increased glycogenolysis. These
      studies indicate that after an overnight fast, basal HGP (glycogenolysis) is
      highly sensitive to the hepatic sinusoidal insulin level.

PMID- 9568683
TI  - Glucagon-like peptide 1(7-36) amide's central inhibition of feeding and
      peripheral inhibition of drinking are abolished by neonatal monosodium glutamate
      treatment.
AB  - In the rat, the glucagon-like peptide 1 (GLP-1)(7-36) amide inhibits neurones in
      the central nervous system responsible for food and water intake. GLP-1-induced
      inhibition of food intake may involve the hypothalamic arcuate nucleus, whereas
      rostral sensory circumventricular organs may be responsible for the inhibitory
      action of GLP-1 on drinking. To further investigate the role of these blood-brain
      barrier-free areas in GLP-1-induced inhibition of ingestive behavior, neonatal
      Wistar rats were subjected to monosodium glutamate (MSG) treatment, which causes
      extensive damage to the arcuate nucleus as well as to parts of the sensory
      circumventricular organs. The inhibitory effect of GLP-1 on feeding induced by
      food deprivation was completely abolished in MSG-lesioned rats. This effect was
      not due to either a loss of sensitivity to anorectic agents or a loss of taste
      aversion because MSG-treated animals displayed normal anorectic responses to
      central administration of corticotropin-releasing factor and normal aversive
      responses to peripheral administration of both lithium chloride and D
      amphetamine. In non-lesioned rats, neuropeptide Y (NPY)-induced feeding was
      significantly reduced by concomitant GLP-1 administration. In contrast, GLP-1 had
      no effect on NPY-induced feeding in MSG-lesioned rats, suggesting that the GLP-1
      receptors that mediate inhibition of feeding are localized upstream to the NPY
      sensitive neurones inducing feeding behavior. The inhibitory effect of GLP-1 on
      water intake was tested using an ANG II-elicited drinking paradigm. Central
      administration of GLP-1 inhibited ANG II drinking in both MSG-treated rats and
      their nontreated littermates. In contrast, peripheral administration of GLP-1 did
      not inhibit ANG II-induced drinking behavior in MSG-treated rats. Thus it is
      evident that centrally acting GLP-1 modulates feeding and drinking behavior via
      neurones sensitive to MSG lesioning in the arcuate nucleus and circumventricular
      organs, respectively.

PMID- 9568684
TI  - Increased expression of mRNA for the long form of the leptin receptor in the
      hypothalamus is associated with leptin hypersensitivity and fasting.
AB  - The responsiveness of the hypothalamus to the inhibitory effects of leptin on
      food intake and body weight is influenced by multiple factors, including
      deficiency of either leptin or leptin receptors (Ob-R). To investigate whether
      altered expression of Ob-R in the hypothalamus could potentially contribute to
      altered leptin sensitivity, we performed in situ hybridization with riboprobes
      that detected either mRNAs encoding both the long (Ob-Rb) and short (Ob-Ra)
      splice variants or mRNA encoding only Ob-Rb. In the arcuate nucleus, mRNA
      encoding Ob-Rb, the predominant signaling form of the receptor, was 2.3 times
      greater in obese db/db and ob/ob mice than in lean +/ob controls (P < 0.01). In
      ob/ob mice, systemic administration of leptin reduced Ob-Rb mRNA content of the
      arcuate nucleus by 30% compared with saline-treated, pair-fed controls (P <
      0.05). A 48-h fast increased Ob-Rb mRNA levels in the arcuate nucleus of normal
      and neuropeptide Y (NPY)-knockout mice (P < 0.01), although the effect was
      greater in the NPY-knockout mice (400 vs. 247%, P < 0.05). In addition, Ob-Rb
      mRNA hybridization was elevated by 40% in the arcuate nucleus (P < 0.05) and by
      75% in the ventromedial nucleus (P < 0.05) of rats fasted 48 h. The results
      suggest that expression of Ob-Rb mRNA in the hypothalamus is sensitive to genetic
      and physiological interventions that alter circulating leptin levels, and that
      overexpression of Ob-Rb in the hypothalamus may contribute to increased leptin
      sensitivity.

PMID- 9568685
TI  - Physiological insulinemia acutely modulates plasma leptin.
AB  - Whether insulin acutely regulates plasma leptin in humans is controversial. We
      examined the dosage-response and time-course characteristics of the effect of
      insulin on leptin in 10 men (age 42+/-2 years [mean+/-SE]; BMI 29.3+/-2.0 kg/m2).
      Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and
      400 mU x m[-2] x min[-1) and a control saline infusion. Although plasma glucose
      and insulin levels remained constant, leptin diminished from 9.1+/-3.0 to 5.9+/
      2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma
      leptin showed a dosage-dependent increase during the insulin infusions that was
      evident within 30-60 min. The insulin-induced increase in leptin was
      proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs)
      decreased during insulin and did not change during saline infusions. ED50 (the
      dose producing half-maximal effect) for insulin's effect on leptin and FFA was
      similar (138+/-36 vs. 102+/-24 pmol/l, respectively; P=0.11). To further define
      the role of physiological insulinemia, we compared the effect of a very low
      dosage insulin infusion (10 mU x m[-2] x min[-1]) with that of a control saline
      infusion in another group of 10 men (mean age 39+/-3 years; BMI 27.1+/-1.0
      kg/m2). Plasma leptin remained stable during that insulin infusion, but fell by
      37+/-2% in the control experiment. Thus physiological insulinemia can acutely
      regulate plasma leptin. Insulin could mediate the effect of caloric intake on
      leptin and could be a determinant of its plasma concentration. Inadequate insulin
      induced leptin production in obese and insulin-resistant subjects may contribute
      to the development or worsening of obesity.

PMID- 9568686
TI  - Bradykinin directly triggers GLUT4 translocation via an insulin-independent
      pathway.
AB  - Physical exercise induces translocation of GLUT4 from an intracellular pool to
      the cell surface in skeletal muscles and increases glucose uptake via an insulin
      independent pathway. However, the molecular mechanism remains to be identified.
      Some studies have suggested that bradykinin is locally released from contracting
      muscles and may be responsible for GLUT4 translocation and the increase of
      glucose transport in skeletal muscles. To determine whether bradykinin directly
      triggers GLUT4 translocation, we established L6 myotubes, 3T3-L1 adipocytes, and
      Chinese hamster ovary cells stably expressing c-myc epitope-tagged GLUT4
      (GLUT4myc) and bradykinin B2 receptors. We found that bradykinin directly
      triggered GLUT4myc translocation and increased the rate of glucose uptake in a
      dose-dependent manner in these cells. The translocation with bradykinin occurred
      even after pretreatment with an islet-activating protein, wortmannin, and phorbol
      12,13-dibutyrate. The signaling pathway does not seem to be mediated by Gi,
      phosphatidylinositol 3-kinase, or protein kinase C. It is insulin-independent and
      via trimeric G-protein Gq. Bradykinin is probably one of the factors responsible
      for exercise-stimulated glucose uptake in skeletal muscles.

PMID- 9568687
TI  - Vascularization of purified pancreatic islet-like cell aggregates (pseudoislets)
      after syngeneic transplantation.
AB  - To clarify whether avascular purified endocrine cell aggregates derived from
      islets of Langerhans (pseudoislets) revascularize similarly to what is known for
      intact pancreatic islet grafts, we studied the process of angiogenesis and
      revascularization of syngeneically transplanted pseudoislets using intravital
      fluorescence microscopy. Pseudoislets were composed of pure beta-cells (B) or non
      beta-cells (NB), as well as of mixed beta- and non-beta-cells (B/NB; 70/30%) or
      nonsorted-cells (NC), and were transplanted into the dorsal skinfold of Syrian
      golden hamsters. Intact islet grafts served as controls. At day 6 after
      transplantation, microvascularization of all types of pseudoislets was found to
      be less than in controls, as indicated by a reduced number of transplants that
      contained newly formed microvessels (take-rate: B, 38.8; NB, 38.7; B/NB, 43.8;
      and NC, 40.3% vs. intact islet grafts, 71.9%; P < 0.01). Moreover, those
      pseudoislets that had developed a microvascular network revealed a significantly
      lower functional capillary density (145.8+/-49.5 to 241.0+/-47.5 cm(-1) vs.
      intact islet grafts: 459.8+/-65.6 cm(-1); P < 0.05). After 20 days, the take-rate
      of pseudoislets was still lower (B, 67.4; NB, 45.3; B/NB, 48.4; and NC, 64.2%)
      when compared with intact islet grafts (88%; P < 0.05); however, islet-like
      aggregates with vascularization now showed an islet-specific glomerulus-like
      network of capillaries with a functional capillary density (498.5+/-49.1 to
      601.4+/-124.0 cm[-1]) similar to that of intact islet grafts (644.3+/-26.8 cm[
      1]). We conclude that the dissociation of pancreatic islets, followed by
      reaggregation of the purified endocrine cells to islet-like clusters
      (pseudoislets), delays the process of angiogenesis and revascularization after
      free transplantation; however, this does not influence the capacity to form an
      intact islet-specific microvasculature (angio-architecture), which appears to be
      independent from the cellular composition of pseudoislets.

PMID- 9568688
TI  - The relationship between humoral and cellular immunity to IA-2 in IDDM.
AB  - Autoantibodies to the neuroendocrine protein insulinoma-associated protein 2 (IA
      2), a member of the tyrosine phosphatase family, have been observed in
      individuals with or at increased risk for IDDM. Because this disease is thought
      to result from a T-cell-mediated autoimmune destruction of the insulin-producing
      pancreatic beta-cells, we analyzed humoral and cellular immune reactivity to this
      autoantigen to further define its role in the pathogenesis of IDDM. Peripheral
      blood mononuclear cells (PBMC) from individuals with newly diagnosed IDDM or at
      varying levels of risk for the disease were stimulated in vitro with the entire
      42-kDa internal domain of IA-2 (amino acids 603-979), a series of control
      antigens (glutathionine-S-transferase, tetanus toxoid, Candida albicans, mumps,
      bovine serum albumin), and a mitogen (phytohemagglutinin). The frequency and mean
      stimulation index of PBMC proliferation against IA-2 was significantly higher in
      newly diagnosed IDDM subjects (14 of 33 [42%]; 3.8+/-4.5 at 10 microg/ml) and
      autoantibody-positive relatives at increased risk for IDDM (6 of 9 [66%]; 3.9+/
      3.2) compared with autoantibody-negative relatives (1 of 15 [7%]; 1.8+/-1.0) or
      healthy control subjects (1 of 12 [8%]; 1.5+/-1.0). The frequencies of cellular
      immune reactivities to all other antigens were remarkably similar between each
      subject group. Sera from 58% of the newly diagnosed IDDM patients tested were IA
      2 autoantibody positive. Despite investigations suggesting an inverse association
      between humoral and cellular immune reactivities against islet-cell-associated
      autoantigens, no such relationship was observed (rs=0.18, P=0.39) with respect to
      IA-2. These studies support the autoantigenic nature of IA-2 in IDDM and suggest
      the inclusion of cellular immune responses as an adjunct marker for the disease.

PMID- 9568689
TI  - The phosphodiesterase inhibitors pentoxifylline and rolipram prevent diabetes in
      NOD mice.
AB  - Interleukin (IL)-12, interferon (IFN)-gamma, and other inflammatory cytokines
      play an important role in the pathogenesis of autoimmune insulitis and diabetes
      in NOD mice, and inhibition of these cytokines is likely to be beneficial. In
      this study, we found that Pentoxifylline (PTX) and Rolipram (phosphodiesterase
      [PDE] inhibitors that induce increased intracellular cAMP) can block inflammatory
      cytokine production. Inhibition of IL-12 and IFN-gamma secretion was demonstrated
      in macrophages activated with lipopolysaccharide or T-cells stimulated through
      the CD3/T-cell receptor complex, respectively. Moreover, strong inhibition of IL
      12 was demonstrated in vivo in superantigen-immunized mice. Rolipram was
      inhibitory at concentrations as low as 10(-8) to 10(-7) mol/l, and on a molar
      basis, it was 100-fold more effective than PTX. Tumor necrosis factor-alpha was
      also inhibited, but IL-4 was less sensitive to suppression. In NOD mice, both PTX
      and Rolipram reduced the severity of insulitis and prevented diabetes, with or
      without cyclophosphamide administration (which precipitates onset of disease).
      This protection of NOD mice was still apparent over 10 weeks after withdrawal of
      the drug treatment. It appears that blocking the activity of type IV PDE is
      sufficient to mediate the effects reported in this study, since Rolipram inhibits
      only this isoform, unlike PTX (a general inhibitor). PTX and Rolipram may be
      effective in the treatment of autoimmune diabetes or other conditions
      characterized by excessive production of inflammatory cytokines.

PMID- 9568690
TI  - Determination of encephalomyocarditis viral diabetogenicity by a putative binding
      site of the viral capsid protein.
AB  - The molecular mechanism by which some, but not all, variants of
      encephalomyocarditis (EMC) virus selectively infect pancreatic beta-cells in mice
      and induce IDDM has been an enigma for more than a decade. We report here that
      the binding site of the EMC viral capsid protein VP1 determines viral
      diabetogenicity. Recombinant chimeric EMC viruses containing threonine, serine,
      proline, aspartic acid, or valine at position 152 of the major capsid protein VP1
      bind poorly to beta-cells. In contrast, recombinant chimeric EMC viruses
      containing alanine or glycine at position 152 of the VP1 bind efficiently to and
      infect beta-cells, resulting in the development of diabetes. Three-dimensional
      molecular modeling reveals that the van der Waals interactions are greater and
      the residues surrounding position 152 of the VP1 are more closely packed in
      recombinant chimeric viruses containing threonine, serine, proline, aspartic
      acid, or valine at position 152 than in recombinant chimeric viruses containing
      alanine or glycine at the same position. Our studies reveal that the surface
      areas surrounding alanine or glycine at position 152 of the VP1 are more
      accessible, thus increasing the availability of the binding sites for attachment
      to beta-cell receptors and resulting in viral infection and the development of
      diabetes.

PMID- 9568691
TI  - Evidence for involvement of the proteasome complex (26S) and NFkappaB in IL-1beta
      induced nitric oxide and prostaglandin production by rat islets and RINm5F cells.
AB  - Interleukin-1beta (IL-1beta) has been implicated as an effector molecule of beta
      cell destruction in autoimmune diabetes. IL-1beta inhibits insulin secretion from
      pancreatic beta-cells by stimulating the expression of inducible nitric oxide
      synthase (iNOS) that generates the free radical nitric oxide. IL-1beta also
      induces the coexpression of the inducible isoform of cyclooxygenase (COX-2) that
      results in the overproduction of proinflammatory prostaglandins. The current
      studies were designed to characterize the involvement of protease(s) in the
      signaling pathway of IL-1beta-induced iNOS and COX-2 expression by rat islets and
      transformed rat pancreatic beta-cells. Because of the limitations of cell numbers
      of purified primary beta-cells obtained from rat islets, biochemical and
      molecular studies were performed using the rat insulinoma beta-cell line RINm5F.
      A serine protease inhibitor, Nalpha-P-tosyl-L-lysine chloromethyl ketone (TLCK),
      and a proteasome complex (26S) inhibitor, MG 132, inhibited IL-1beta-induced
      nitrite formation, an oxidation product of nitric oxide produced by iNOS, in a
      concentration-dependent manner, with complete inhibition observed at 100
      micromol/l and 10 micromol/l, respectively. Both TLCK and MG 132 also inhibited
      iNOS gene expression at the level of mRNA and protein. In an analogous manner,
      TLCK (100 micromol/l) and MG 132 (10 micromol/l) inhibited IL-1beta-induced COX-2
      enzyme activity (PGE2 formation) and COX-2 gene expression at the level of mRNA
      and protein. In human islets, the proteasome inhibitor MG 132 also inhibited the
      formation of the products of iNOS and COX-2 enzyme activity, nitrite, and PGE2,
      respectively. These findings suggest that the inhibitory action of TLCK and MG
      132 on iNOS and COX-2 expression precedes transcription. The transcription factor
      NFkappaB is essential for activation of a number of cytokine-inducible enzymes
      and was evaluated as a possible site of protease action necessary for IL-1beta
      induced coexpression of iNOS and COX-2. TLCK and MG 132 inhibited both IL-1beta
      induced activation of NFkappaB and degradation of IkappaBalpha by islets and
      RINm5F cells. These results implicate protease activation as an early signaling
      event in IL-1beta-induced inhibition of beta-cell function. This study also
      suggests that IL-1beta-induced iNOS and COX-2 coexpression by pancreatic beta
      cells share a common signaling pathway in utilizing the proteasome complex (26S)
      and the transcription factor NFkappaB, and it identifies sites of intervention to
      prevent the overproduction of their inflammatory products.

PMID- 9568692
TI  - GADIA2-combi determination as first-line screening for improved prediction of
      type 1 diabetes in relatives.
AB  - A new radiobinding assay for the simultaneous detection of antibodies to GAD and
      the tyrosine phosphatase IA2 has been recently described in patients with newly
      diagnosed type 1 diabetes. Here we assessed sensitivity and predictive value of
      this GADIA2-combi test in first-degree relatives of type 1 diabetic patients
      compared with islet cell antibody (ICA) and insulin autoantibody (IAA) screening.
      Of 1,606 relatives, 77 (4.8%) had elevated GADIA2-combi titers above the 99th
      percentile of 105 nondiabetic control subjects, and results were confirmed by
      testing these samples for GAD antibody (GADA) and tyrosine phosphatase IA2
      antibody (IA2A) in the single antibody test (29 GADA+/IA2A+, 44 GADA+/IA2A-, and
      4 IA2A+/GADA-). A further 9 of 1,606 relatives had detectable ICA (1) or IAA (8),
      but they were negative in the GADIA2-combi assay as well as in the single test
      for GADA or IA2A. Twenty-four relatives progressed to IDDM within a median follow
      up time of 5.6 years (range 0.5-8.2). The sensitivity of antibody determination
      in relatives with progression to IDDM was 92% for the GADIA2-combi assay, 96% for
      the combined testing of IAA and GADIA2-combi antibodies, and 83, 67, 67, and 79%,
      respectively, for GADA, IA2A, IAA, or ICA testing alone. The cumulative life
      table risk of antibody-positive relatives was related to GADIA2-combi titers (5
      year risk: >50 U, 51% [95% CI 30-73]; >10 to 50 U, 12% [1-24]; <10 U, 0.17% [0
      0.5]; P=0.0001) and on the presence of IA2A in addition to GADA (5-year risk:
      GADA+/IA2A+, 47% [25-68]; GADA+/IA2A-, 15% [2-28]; P=0.006). In those with
      detectable antibodies, risk was not associated with age (<15 vs. >15 years) or
      relation to proband (offspring, sibling, parent). Relatives with GADIA2-combi
      antibodies >10 U and the additional presence of IAA had a slightly higher
      diabetes risk than relatives without IAA (5-year: IAA+, 46% [23-68]; IAA-, 19% [6
      32]; P=0.07). Furthermore, low first-phase insulin release after intravenous
      glucose tolerance test was associated with risk in relatives with GADIA2-combi
      antibodies (P=0.01). These results indicate that the GADIA2-combi test is a
      valuable marker for first-line screening and risk assessment of type 1 diabetes
      in relatives. It can be used for venous as well as capillary blood samples.

PMID- 9568693
TI  - Decreased tolbutamide-stimulated insulin secretion in healthy subjects with
      sequence variants in the high-affinity sulfonylurea receptor gene.
AB  - The high-affinity sulfonylurea receptor (SUR1) is, as a subunit of the ATP
      sensitive potassium channel, an important regulator of insulin secretion in the
      pancreatic beta-cell. The aim of this study was to examine if genetic variability
      of the SUR1 gene was associated with NIDDM or altered pancreatic beta-cell
      function. Mutational analysis of all the 39 SUR1 exons, including intron-exon
      boundaries, in 63 NIDDM patients revealed two missense variants, five silent
      variants in the coding region, and four intron variants. The two missense
      variants (Asp673Asn and Ser1369Ala) and two sequence variants (ACC-->ACT,
      Thr759Thr and a c-->t intron variant in position -3 of the exon 16 splice
      acceptor site) were examined for association with NIDDM and for a possible
      influence on insulin and C-peptide secretion after intravenous glucose and
      tolbutamide loads in a random sample of unrelated, healthy, young Danish
      Caucasians. The Asp673Asn variant in exon 14 was only identified in one NIDDM
      patient, and the allelic frequency of the Ser1369Ala was similar among 247
      control subjects (0.38 [95% CI 0.34-0.42]) and 406 NIDDM patients (0.40 [0.37
      0.43]). The allelic frequency of the silent exon 18 Thr775Thr variant was 0.051
      (0.035-0.067) in NIDDM patients (n=392) and 0.027 (0.013-0.041) in control
      subjects (n=246; chi2=4.99, P=0.03). The allelic frequency of the intron variant
      was similar among NIDDM patients (0.45 [0.42-0.48]) and control subjects (0.44
      [0.40-0.48]). Of 386 NIDDM patients, 17 had the combined genotype exon 18 C/T and
      intron -3c/-3t (0.044 [0.024-0.064]), whereas 3 of 243 control subjects had the
      same combined genotype (0.012 [0-0.026]; chi2=4.87, P=0.03; odds ratio: 3.69
      [1.07-12.71]). Of 380 unrelated, healthy, young Danish Caucasians, 10 (0.026
      [0.010-0.042]) had the combined at-risk genotype. These subjects had, on average,
      a 50% reduction in serum C-peptide and a 40% reduction in serum insulin responses
      upon tolbutamide injection (P=0.002 and P=0.05, respectively) but normal serum C
      peptide and insulin responses upon glucose injection. In conclusion, a silent
      polymorphism in exon 18 of the SUR1 gene is associated with NIDDM in a Danish
      Caucasian population. In combination with an intron variant, the association is
      higher, and young, healthy carriers of the intragenic combination have reduced
      serum C-peptide and insulin responses to a tolbutamide load.

PMID- 9568694
TI  - Differentiation between glucose-induced desensitization of insulin secretion and
      beta-cell exhaustion in the HIT-T15 cell line.
AB  - Refractoriness of the pancreatic beta-cell to glucose stimulation plays a role in
      the secretory defect of NIDDM, but the mechanisms underlying this refractoriness
      are not clear. The purpose of this study was to determine whether the HIT-T15
      pancreatic beta-cell line can be used as an investigative model for
      refractoriness of glucose-induced insulin secretion and, if so, whether the
      mechanism for this refractoriness involves alteration in stimulus-secretion
      coupling (desensitization) or results from exhaustion of insulin stores. In
      perifusion experiments, acute insulin responses (AIRs) in HIT-T15 cells
      progressively diminished during consecutive 5-min glucose (11.1 mmol/l) pulses
      (G) given every 20 min (G1=9.2+/-1.3, G2=4.1+/-1.0, G3=2.7+/-0.7, G4=2.5+/-1.1
      microU/ml). To determine whether this refractoriness for glucose extended to the
      potentiating effects of glucose on nonglucose secretagogues, cells were
      challenged with arginine after desensitization with glucose. In HIT-T15 cells,
      the response to the arginine pulse (16.7+/-5.2 microU/ml) after three glucose
      pulses was significantly less (P < 0.01) than the response to a control arginine
      pulse (29.6+/-12.1 microU/ml) preceded by an infusion of buffer in the absence of
      glucose pulses. Variable rest periods after desensitization allowed recovery of
      the AIR in HIT-T15 cells; responses 30, 60, 90, and 120 min after the
      desensitization procedure increased in a stepwise fashion (3.8+/-2.7, 4.5+/-2.7,
      7.8+/-5.2, and 9.7+/-5.3 microU/ml, respectively). To differentiate
      desensitization from exhaustion of insulin stores, studies were performed in the
      presence of epinephrine, a potent inhibitor of insulin secretion. In HIT-T15
      cells, after three pulses of glucose during the epinephrine infusion, epinephrine
      was discontinued and the insulin response to a fourth pulse was assessed. The G4
      AIR (1.9+/-0.6 microU/ml) was markedly less than a control G4 AIR (5.4+/-1.2
      microU/ml) that followed an epinephrine infusion alone with no concurrent glucose
      pulses. Beta-cell refractoriness was also induced in the HIT-T15 cell using 45
      min steady-state infusions of glucose. Cells were exposed to a 45-min infusion of
      either 3.7 or 11.1 mmol/l glucose, rested for 20 min in the absence of glucose,
      and then challenged with a 5-min, 11.1 mmol/l glucose pulse. In both cases, the
      AIR to the 5-min pulse (10.2+/-5.1 and 2.9+/-1.4 microU/ml after the 3.7 and 11.1
      mmol/l infusion, respectively) was lower than the AIR to a control pulse (27.4+/
      5.9 microU/ml) not preceded by glucose infusion. These studies demonstrated that
      the HIT-T15 cell line is an appropriate model for studying mechanisms of beta
      cell refractoriness to glucose signaling. The short-term intensive glucose
      stimulation paradigms used in our studies induced an abnormality in insulin
      secretion that is consistent with desensitization but not beta-cell exhaustion.

PMID- 9568695
TI  - Sulfate content and specific glycosaminoglycan backbone of perlecan are critical
      for perlecan's enhancement of islet amyloid polypeptide (amylin) fibril
      formation.
AB  - Islet amyloidosis is characterized by the deposition and accumulation of amylin
      in pancreatic beta-cells and is observed in 90% of patients with type 2 diabetes.
      Previous studies have also revealed the presence of the specific heparan sulfate
      proteoglycan, perlecan, colocalized to islet amyloid deposits, similar to
      perlecan's known involvement with other amyloid proteins. In the present study,
      perlecan purified from the Engelbreth-Holm-Swarm (EHS) tumor was used to define
      perlecan's interactions with amylin (i.e., islet amyloid polypeptide) and its
      effects on amylin fibril formation. Using a solid phase-binding immunoassay,
      human amylin, but not rat amylin, bound immobilized EHS perlecan with a single
      dissociation constant (Kd) = 2.75 x 10(-6) mol/l. The binding of human amylin to
      perlecan was similarly observed using perlecan heparan sulfate glycosaminoglycans
      (GAGs), and was completely abolished by 10 micromol/l heparin. Using thioflavin T
      fluorometry, Congo red staining, and electron microscopy methodology, intact
      perlecan was found to enhance amylin fibril formation in a dosage-dependent
      manner, with the majority of these effects attributed to the heparan sulfate GAG
      chains of perlecan. Other sulfated GAGs and related macromolecules were also
      effective in the enhancement of amylin fibril formation in the order of heparin >
      heparan sulfate > chondroitin-4-sulfate = dermatan sulfate = dextran sulfate >
      pentosan polysulfate, implicating the importance of the specific GAG/carbohydrate
      backbone. The sulfate content of heparin/heparan sulfate was also important for
      the enhancement of amylin fibril formation in the order of heparin > N-desulfated
      N-acetylated heparin > completely desulfated N-sulfated heparin > completely
      desulfated N-acetylated heparin. These studies suggest that the enhancement
      effects of perlecan on amylin fibril formation are mediated primarily by both
      specific GAG chain backbone and GAG sulfate content, and implicate perlecan as an
      important macromolecule that is likely involved in the pathogenesis of islet
      amyloidosis.

PMID- 9568696
TI  - Creation and characterization of a mitochondrial DNA-depleted pancreatic beta
      cell line: impaired insulin secretion induced by glucose, leucine, and
      sulfonylureas.
AB  - It has been proposed that mitochondrial oxidative phosphorylation in pancreatic
      beta-cells plays an important role in insulin secretion. To examine the impact of
      mitochondrial dysfunction on insulin secretion, we created a MIN6 cell line that
      depleted mitochondrial DNA (mtDNA) by treatment with ethidium bromide (EtBr), and
      studied the response of the cell line to various secretagogues. MIN6 cells
      cultured with 0.5 microg/ml EtBr for over 2 months (termed MIN6 deltamt cells)
      revealed a marked (>90%) decrease in mtDNA content and a lack of mRNAs encoded by
      mtDNA. MIN6 deltamt cells showed the defects of cytochrome c oxidase activity,
      glucose- and leucine-induced increase in cellular ATP content, and respiratory
      chain-driven ATP synthesis, suggesting that MIN6 deltamt cells lost oxidative
      phosphorylation activity due to the selective disruption of the subunits of
      respiratory chain enzymes encoded by mtDNA. MIN6 deltamt cells also showed a
      decrease in glucose utilization, suggesting the impairment of the glycolytic
      pathway as well. After stimulation with glucose and leucine, MIN6 deltamt cells
      showed no response in insulin secretion or intracellular free Ca2+ concentration
      ([Ca2+]i). On the other hand, arginine stimulated insulin secretion and an
      increase in [Ca2+]i in MIN6 deltamt cells as in MIN6 cells. Glibenclamide also
      stimulated insulin secretion and an increase in [Ca2+]i in both types of cells,
      but the responses of MIN6 deltamt cells were significantly lower than those of
      MIN6 cells. These results suggest the importance of ATP production in insulin
      secretion and an increase in [Ca2+]i, both induced by glucose and leucine.
      Moreover, mitochondrial function turns out to be not essential but important for
      the activation of sulfonylurea-induced insulin secretion.

PMID- 9568697
TI  - Identification of glucagon-like peptide 1 (GLP-1) actions essential for glucose
      homeostasis in mice with disruption of GLP-1 receptor signaling.
AB  - Glucagon-like peptide-1 (GLP-1) acts to control blood glucose via multiple
      mechanisms, including regulation of insulin and glucagon secretion, gastric
      emptying, satiety, and peripheral insulin sensitivity. However, the relative
      importance of these actions for regulation of blood glucose remains unclear. We
      demonstrate here a gene dosage effect for the incretin action of GLP-1, as
      heterozygous GLP-1R +/- mice exhibit an abnormal glycemic response to oral
      glucose challenge in association with reduced circulating levels of glucose
      stimulated insulin. In contrast, GLP-1 signaling is not required for normal
      control of fasting and postabsorptive glucagon levels, and no significant changes
      were detected in the tissue content of pancreatic and intestinal proglucagon
      mRNA, glucagon-like immunoreactivity, or GLP-1 in GLP-1R -/- or +/- mice. Despite
      the demonstration that GLP-1 stimulates proinsulin gene transcription, pancreatic
      insulin mRNA transcripts were similar in wild-type and GLP-1R -/- mice.
      Furthermore, despite suggestions that GLP-1 regulates peripheral glucose
      disposal, whole-body glucose utilization was similar in wild-type and GLP-1R -/-
      mice under both basal and hyperinsulinemic conditions. These observations
      demonstrate that of the numerous physiological activities ascribed to GLP-1, only
      the incretin effect on pancreatic beta-cells appears essential for regulation of
      glucose homeostasis in vivo.

PMID- 9568698
TI  - Reduced amylin release is a characteristic of impaired glucose tolerance and type
      2 diabetes in Japanese Americans.
AB  - Islet amyloid is a characteristic feature of type 2 diabetes. Its major component
      is the normal beta-cell secretory product amylin, or islet amyloid polypeptide
      (IAPP). To determine whether increased or disproportionate release of amylin may
      explain the propensity for amyloid deposition in type 2 diabetes, we measured
      plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI)
      release in response to an oral glucose load in 94 Japanese-American subjects with
      normal glucose tolerance (NGT; n=56), impaired glucose tolerance (IGT; n=10), and
      type 2 diabetes (n=28) as defined by World Health Organization criteria. The
      incremental increase in ALI, IRI, and glucose (G) at 30 min after oral glucose
      ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures
      of beta-cell function. Overall glucose metabolism was assessed as the incremental
      glucose area (glucose AUC) during the 2 h of the oral glucose tolerance test. As
      expected, plasma glucose concentrations at both fasting (NGT, 5.0+/-0.4; IGT,
      5.5+/-0.1; type 2 diabetes, 6.2+/-0.3 mmol/l; P < 0.0001) and 2 h (NGT, 6.7+/
      0.1; IGT, 9.4+/-0.3; type 2 diabetes, 13.2 +/-0.5 mmol/l; P < 0.0001) were
      elevated in individuals with IGT and type 2 diabetes. In response to glucose
      ingestion, plasma IRI and ALI increased in all subjects, but these increments
      were lower in individuals with reduced glucose tolerance, as reflected in the
      deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4
      pmol/l; P < 0.0001) and deltaALI/deltaG (NGT, 2.6+/-0.2; IGT, 1.8+/-0.3; type 2
      diabetes, 1.2+/-0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min
      incremental ALI and IRI responses were proportionate such that the molar ratio of
      ALI to IRI was not different among the three groups (NGT, 2.6+/-0.2; IGT, 2.9 +/
      0.3; type 2 diabetes, 2.9+/-0.3%; NS). Further, the relationship between beta
      cell function, measured as either deltaIRI/deltaG or deltaALI/deltaG, and glucose
      metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2
      values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. We conclude that
      the reduced beta-cell function of IGT and type 2 diabetes includes proportionate
      reductions in both IRI and ALI release. Thus, it is unlikely that the development
      of islet amyloid in type 2 diabetes is the result of increased release of ALI.

PMID- 9568699
TI  - Mouse pancreatic beta-cells exhibit preserved glucose competence after disruption
      of the glucagon-like peptide-1 receptor gene.
AB  - Previous work suggested that glucagon-like peptide 1 (GLP-1) can acutely regulate
      insulin secretion in two ways, 1) by acting as an incretin, causing amplification
      of glucose-induced insulin release when glucose is given orally as opposed to
      intravenous glucose injection; and 2) by keeping the beta-cell population in a
      glucose-competent state. The observation that mice with homozygous disruption of
      the GLP-1 receptor gene are diabetic with a diminished incretin response to
      glucose underlines the first function in vivo. Isolated islets of Langerhans from
      GLP-1 receptor -/- mice were studied to assess the second function in vitro.
      Absence of pancreatic GLP-1 receptor function was observed in GLP-1 receptor -/-
      mice, as exemplified by loss of [125I]GLP-1 binding to pancreatic islets in situ
      and by the lack of GLP-1 potentiation of glucose-induced insulin secretion from
      perifused islets. Acute glucose competence of the beta-cells, assessed by
      perifusing islets with stepwise increases of the medium glucose concentration,
      was well preserved in GLP-1 receptor -/- islets in terms of insulin secretion.
      Furthermore, neither islet nor total pancreatic insulin content was significantly
      changed in the GLP-1 receptor -/- mice when compared with age-and sex-matched
      controls. In conclusion, mouse islets exhibit preserved insulin storage capacity
      and glucose-dependent insulin secretion despite the loss of functional GLP-1
      receptors. The results demonstrate that the glucose responsiveness of islet beta
      cells is well preserved in the absence of GLP-1 receptor signaling.

PMID- 9568700
TI  - Reversibility of retinal flow abnormalities is disease-duration dependent in
      diabetic rats.
AB  - Decreased retinal blood flow has been measured in streptozotocin (STZ)-induced
      diabetes of 1 week's duration, and primary insulin intervention was effective in
      maintaining normal retinal blood flow in diabetic rats. Retinal blood-flow
      abnormalities precede clinical diabetic retinopathy in both diabetic animals and
      patients. An important characteristic of diabetic retinopathy is the difficulty
      of reversibility once it has been established. Because altered retinal
      hemodynamics is a possible marker of early diabetic retinopathy, we investigated
      in this study whether retinal blood-flow changes in rats can be normalized by
      secondary insulin intervention following short and chronic periods of untreated
      STZ-induced diabetes. Subcutaneous insulin pumps were placed into diabetic rats
      for 1 week after 1 week of diabetes (2-week group) and after 3 weeks of diabetes
      (4-week group). Retinal circulatory parameters were determined using image
      analysis of video fluorescein angiogram recordings. For the 2-week group, retinal
      blood flow was significantly (P < 0.05) reduced in the untreated diabetic rats
      compared with nondiabetic and insulin-treated diabetic rats (80.6+/-29.2, 131.9+/
      50.1, and 151.3+/-54.0 pixels2/s respectively). Retinal blood flow was also
      significantly (P < 0.05) reduced in the 4-week untreated diabetic rats compared
      with nondiabetic rats (95.7+/-22.2 vs. 125.7+/-29.5 pixels2/s). In contrast to
      the shorter-duration group, insulin treatment for 1 week after 3 weeks of
      diabetes did not totally normalize retinal blood flow (117.5+/-32.4 pixels2/s).
      These results suggest that vascular abnormalities could become more resistant to
      normalization following short-term (1 week) insulin treatment after longer
      periods of untreated diabetes.

PMID- 9568701
TI  - Early activation of vascular endothelium in nonobese, nondiabetic essential
      hypertensive patients with multiple metabolic abnormalities.
AB  - Circulating soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1), and
      vascular adhesion molecule-1 (VCAM-1) concentrations were evaluated in 93
      nonobese essential hypertensive patients, of whom 16 had impaired glucose
      tolerance and hyperlipidemia (group I); 25 had impaired glucose tolerance (group
      II); 28 had hyperlipidemia (group III); and 24 had no metabolic abnormalities
      (group IV). A group of 22 healthy volunteers served as a control group. All
      groups were without clinical or ultrasound evidence of vascular lesion and were
      matched for age, sex, and BMI. Endothelial soluble adhesion molecules were
      measured at baseline, during an oral glucose tolerance test, and after 12 weeks
      of either enalapril or placebo treatments. Plasma soluble E-selectin, ICAM-1, and
      VCAM-1 were higher (P < 0.05) in group I and II than in the other groups (group
      I: E-selectin, 96.1+/-27.1; ICAM-1, 304.0+/-102.1; VCAM-1, 626.1+/-156.2
      microg/l. Group II: E-selectin, 88.0+/-18.0; ICAM-1, 268.0+/-84.1; VCAM-1,
      594.1+/-140.9 microg/I. Group III: E-selectin, 70.1+/-18.1; ICAM-1, 195.1+/-68.0;
      VCAM-1, 495.9+/-110.1 microg/l. Group IV: E-selectin, 65.1+/-16.1; ICAM-1,
      168.1+/-64.0; VCAM-1, 472.1+/-108.2 microg/l). Soluble adhesins levels were not
      higher than normal in groups III and IV. Plasma soluble ICAM-1 concentrations
      increased in group I after glucose administration and were directly correlated
      with 2-h insulin levels (r=0.648, P=0.007). Compared with placebo, 12 weeks of
      enalapril treatment significantly (P < 0.0001) reduced soluble E-selectin, ICAM
      1, and VCAM-1. Decrements of soluble adhesins were not dependent on enalapril
      related blood pressure changes. Therefore, an early endothelial activation was
      present in essential hypertensive patients with impaired glucose tolerance,
      regardless of the presence of hyperlipidemia. ACE inhibition counteracted such
      endothelial activation.

PMID- 9568702
TI  - Altered expression and subcellular localization of diacylglycerol-sensitive
      protein kinase C isoforms in diabetic rat glomerular cells.
AB  - Protein kinase C (PKC) is implicated in the pathogenesis of diabetic nephropathy.
      This study was designed to identify the expression of diacylglycerol (DAG)
      sensitive PKC-alpha, -betaII, -delta, and -epsilon isoforms in normal and
      diabetic rat glomerular cells and to determine the effects of high glucose and
      insulin on PKC isoform cellular compartmentalization and PKC activity. Diabetic
      rats treated with or without insulin and normal rats were examined 2 and 4 weeks
      after streptozotocin/vehicle injection. Renal cortical tissue immunogold-labeled
      with anti-PKC-alpha, -betaII, -delta, or -epsilon antibody was visualized by
      electron microscopy. From isolated glomeruli, total cell lysate and cytosol and
      membrane fractions were immunoblotted with the same anti-PKC isoform antibodies.
      PKC activity in isolated glomeruli was measured by 32P-phosphorylation of the
      epidermal growth factor (EGF)-receptor substrate. Immunogold labeling revealed
      expression of the four PKC isoforms by glomerular visceral epithelial,
      endothelial, and mesangial cells of both normal and diabetic rats. Immunoblot
      analysis of the diabetic rat glomeruli at 2 weeks demonstrated a significant
      increase in membrane-associated PKC-alpha, -delta, and -epsilon and a significant
      decrease in membrane PKC-betaII content compared with normal, which were similar
      at 4 weeks. Insulin treatment normalized membrane PKC isoform contents and caused
      a significant decrease in the cytosol content of PKC-alpha, -betaII, and -delta
      and total cellular PKC-alpha compared with normal. Although PKC activity in the
      cells of diabetic rat glomeruli was increased by 20% compared with normal, the
      difference did not reach statistical significance. In insulin-treated diabetic
      rat glomeruli, PKC activity was significantly decreased compared with non-insulin
      treated diabetic rat glomeruli. In conclusion, DAG-sensitive PKC-alpha, -betaII, 
      delta, and -epsilon isoforms are all found in the three major glomerular cell
      types in rats, and the expression, compartmentalization, and activity are
      modulated independently by high glucose and insulin.

PMID- 9568703
TI  - Antioxidants diminish developmental damage induced by high glucose and
      cyclooxygenase inhibitors in rat embryos in vitro.
AB  - Previous studies have suggested that the metabolism of arachidonic acid and
      radical oxygen species (ROS) are altered in diabetes and that these disturbances
      may induce severe embryonic dysmorphogenesis in diabetic pregnancy. We tested
      this hypothesis by studying whether an inhibition of the rate-limiting enzyme of
      prostaglandin biosynthesis, cyclooxygenase (COX), caused developmental
      disturbances analogous to those seen in embryos exposed to high glucose
      concentration. Whether antioxidants could prevent such developmental alterations
      was also investigated. Whole embryo culture was used in which day-9 embryos were
      exposed to high concentrations of glucose, arachidonic acid, prostaglandin
      (PG)E2, COX inhibitors, and antioxidants for 48 h. Increased glucose
      concentration (from 10 to 30 mmol/l) caused embryonic dysmorphogenesis, and
      addition of either 60 pmol/l arachidonic acid or 280 nmol/l PGE2 largely
      protected the embryo from this maldevelopment. Furthermore, exposure to the COX
      inhibitors indomethacin (200 micromol/l) or acetylsalicylic acid (700 micromol/l)
      in 10 mmol/l glucose concentration yielded embryonic dysmorphogenesis similar to
      that caused by 30 mmol/l glucose. Supplementation of either arachidonic acid or
      PGE2 to the culture medium with COX inhibitors in low glucose rectified the
      embryonic development, and PGE2 supplementation also normalized the development
      of embryos cultured with COX inhibitors in high glucose concentration.
      Interestingly, the antioxidants superoxide dismutase (SOD) and N-acetylcysteine
      (NAC) were each able to diminish the dysmorphogenesis induced by the COX
      inhibitors, at doses previously shown to diminish glucose-induced embryonic
      damage in the same in vitro culture system. In conclusion, the present study
      shows that a high glucose concentration disturbs embryonic development and that
      this disturbance may be partly mediated via altered metabolism of arachidonic
      acid and ROS in the embryo.

PMID- 9568705
TI  - Vitamin D receptor gene polymorphisms influence insulin secretion in Bangladeshi
      Asians.

PMID- 9568704
TI  - Structure and organization of the human uncoupling protein 2 gene and
      identification of a common biallelic variant in Caucasian and African-American
      subjects.

PMID- 9568706
TI  - BRL 49653 blocks the lipolytic actions of tumor necrosis factor-alpha: a
      potential new insulin-sensitizing mechanism for thiazolidinediones.
AB  - Thiazolidinediones (TZDs) such as BRL 49653 are a class of antidiabetic agents
      that are agonists for the peroxisome proliferator-activated nuclear receptor
      (PPAR-gamma2). In vivo, TZDs reduce circulating levels of free fatty acids (FFAs)
      and ameliorate insulin resistance in individuals with obesity and NIDDM.
      Adipocyte production of TNF-alpha is proposed to play a role in the development
      of insulin resistance, and because BRL 49653 has been shown to antagonize some of
      the effects of TNF-alpha, we examined the effects of TNF-alpha and BRL 49653 on
      adipocyte lipolysis. After a 24-h incubation of TNF-alpha (10 ng/ml) with 3T3-L1
      adipocytes, glycerol release increased by approximately 7-fold, and FFA release
      increased by approximately 44-fold. BRL 49653 (10 pmol/l) reduced TNF-alpha
      induced glycerol release by approximately 50% (P < 0.001) and FFA release by
      approximately 90% (P < 0.001). BRL 49653 also reduced glycerol release by
      approximately 50% in adipocytes pretreated for 24 h with TNF-alpha. Prolonged
      treatment (5 days) with either BRL 49653 or another PPAR-gamma2 agonist, 15-d
      delta-12,14-prostaglandin J2 (15-d deltaPGJ2), blocked TNF-alpha-induced glycerol
      release by approximately 100%. Catecholamine (isoproterenol)-stimulated lipolysis
      was unaffected by BRL 49653 and 15-d deltaPGJ2. BRL 49653 partially blocked the
      TNF-alpha-mediated reduction in protein levels of hormone-sensitive lipase and
      perilipin A, two proteins involved in adipocyte lipolysis. These data suggest a
      novel pathway that may contribute to the ability of the TZDs to reduce serum FFA
      and increase insulin sensitivity.

PMID- 9568707
TI  - Conserved themes but novel activities in recombinases and topoisomerases.

PMID- 9568708
TI  - PPARgamma in monocytes: less pain, any gain?

PMID- 9568709
TI  - Endocrine disruptors signal the need for receptor models and mechanisms to inform
      policy.

PMID- 9568710
TI  - Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation
      and activation.
AB  - The ligand for osteoprotegerin has been identified, and it is a TNF-related
      cytokine that replaces the requirement for stromal cells, vitamin D3, and
      glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand
      (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the
      osteoclast lineage and stimulates the rapid induction of genes that typify
      osteoclast development. OPGL directly activates isolated mature osteoclasts in
      vitro, and short-term administration into normal adult mice results in osteoclast
      activation associated with systemic hypercalcemia. These data suggest that OPGL
      is an osteoclast differentiation and activation factor. The effects of OPGL are
      blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key
      extracellular regulators of osteoclast development.

PMID- 9568711
TI  - Somatic inactivation of Pkd2 results in polycystic kidney disease.
AB  - Germline mutations in PKD2 cause autosomal dominant polycystic kidney disease. We
      have introduced a mutant exon 1 in tandem with the wild-type exon 1 at the mouse
      Pkd2 locus. This is an unstable allele that undergoes somatic inactivation by
      intragenic homologous recombination to produce a true null allele. Mice
      heterozygous and homozygous for this mutation, as well as Pkd+/- mice, develop
      polycystic kidney and liver lesions that are indistinguishable from the human
      phenotype. In all cases, renal cysts arise from renal tubular cells that lose the
      capacity to produce Pkd2 protein. Somatic loss of Pkd2 expression is both
      necessary and sufficient for renal cyst formation in ADPKD, suggesting that PKD2
      occurs by a cellular recessive mechanism.

PMID- 9568712
TI  - Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic
      mice.
AB  - To investigate the roles of astroglial cells, we targeted their ablation
      genetically. Transgenic mice were generated expressing herpes simplex virus
      thymidine kinase from the mouse glial fibrillary acidic protein (GFAP) promoter.
      In adult transgenic mice, 2 weeks of subcutaneous treatment with the antiviral
      agent ganciclovir preferentially ablated transgene-expressing, GFAP-positive glia
      from the jejunum and ileum, causing a fulminating and fatal jejuno-ileitis. This
      pathology was independent of bacterial overgrowth and was characterized by
      increased myeloperoxidase activity, moderate degeneration of myenteric neurons,
      and intraluminal hemorrhage. These findings demonstrate that enteric glia play an
      essential role in maintaining the integrity of the bowel and suggest that their
      loss or dysfunction may contribute to the cellular mechanisms of inflammatory
      bowel disease.

PMID- 9568713
TI  - Expression of amino-terminally truncated PrP in the mouse leading to ataxia and
      specific cerebellar lesions.
AB  - The physiological role of prion protein (PrP) remains unknown. Mice devoid of PrP
      develop normally but are resistant to scrapie; introduction of a PrP transgene
      restores susceptibility to the disease. To identify the regions of PrP necessary
      for this activity, we prepared PrP knockout mice expressing PrPs with amino
      proximal deletions. Surprisingly, PrP lacking residues 32-121 or 32-134, but not
      with shorter deletions, caused severe ataxia and neuronal death limited to the
      granular layer of the cerebellum as early as 1-3 months after birth. The defect
      was completely abolished by introducing one copy of a wild-type PrP gene. We
      speculate that these truncated PrPs may be nonfunctional and compete with some
      other molecule with a PrP-like function for a common ligand.

PMID- 9568714
TI  - A calcineurin-dependent transcriptional pathway for cardiac hypertrophy.
AB  - In response to numerous pathologic stimuli, the myocardium undergoes a
      hypertrophic response characterized by increased myocardial cell size and
      activation of fetal cardiac genes. We show that cardiac hypertrophy is induced by
      the calcium-dependent phosphatase calcineurin, which dephosphorylates the
      transcription factor NF-AT3, enabling it to translocate to the nucleus. NF-AT3
      interacts with the cardiac zinc finger transcription factor GATA4, resulting in
      synergistic activation of cardiac transcription. Transgenic mice that express
      activated forms of calcineurin or NF-AT3 in the heart develop cardiac hypertrophy
      and heart failure that mimic human heart disease. Pharmacologic inhibition of
      calcineurin activity blocks hypertrophy in vivo and in vitro. These results
      define a novel hypertrophic signaling pathway and suggest pharmacologic
      approaches to prevent cardiac hypertrophy and heart failure.

PMID- 9568715
TI  - Oxidized LDL regulates macrophage gene expression through ligand activation of
      PPARgamma.
AB  - Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play
      a central role in foam cell formation and the pathogenesis of atherosclerosis. We
      demonstrate here that oxLDL activates PPARgamma-dependent transcription through a
      novel signaling pathway involving scavenger receptor-mediated particle uptake.
      Moreover, we identify two of the major oxidized lipid components of oxLDL, 9-HODE
      and 13-HODE, as endogenous activators and ligands of PPARgamma. Our data suggest
      that the biologic effects of oxLDL are coordinated by two sets of receptors, one
      on the cell surface, which binds and internalizes the particle, and one in the
      nucleus, which is transcriptionally activated by its component lipids. These
      results suggest that PPARgamma may be a key regulator of foam cell gene
      expression.

PMID- 9568716
TI  - PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized
      LDL.
AB  - The formation of foam cells from macrophages in the arterial wall is
      characterized by dramatic changes in lipid metabolism, including increased
      expression of scavenger receptors and the uptake of oxidized low-density
      lipoprotein (oxLDL). We demonstrate here that the nuclear receptor PPARgamma is
      induced in human monocytes following exposure to oxLDL and is expressed at high
      levels in the foam cells of atherosclerotic lesions. Ligand activation of the
      PPARgamma:RXRalpha heterodimer in myelomonocytic cell lines induces changes
      characteristic of monocytic differentiation and promotes uptake of oxLDL through
      transcriptional induction of the scavenger receptor CD36. These results reveal a
      novel signaling pathway controlling differentiation and lipid metabolism in
      monocytic cells, and suggest that endogenous PPARgamma ligands may be important
      regulators of gene expression during atherogenesis.

PMID- 9568717
TI  - Localized requirements for windbeutel and pipe reveal a dorsoventral prepattern
      within the follicular epithelium of the Drosophila ovary.
AB  - Establishment of dorsoventral polarity within the Drosophila embryo requires
      extraembryonic positional information generated during oogenesis. The genes
      windbeutel, pipe, and nudel are required within the somatic follicle cells of the
      ovary for production of this spatial cue. Using a novel follicle cell marker
      system, we have directly evaluated the effect of mutant follicle cell clones on
      the embryonic dorsoventral pattern. We find no spatially localized requirement
      for nudel activity. In contrast, windbeutel and pipe are required only within a
      restricted ventral region of the follicular epithelium. This ventral region can
      determine lateral embryonic cell fates nonautonomously, indicating that spatial
      information originating ventrally is subsequently refined, perhaps via diffusion,
      to yield the gradient of positional information that determines the embryonic
      dorsoventral pattern.

PMID- 9568718
TI  - COPII-coated vesicle formation reconstituted with purified coat proteins and
      chemically defined liposomes.
AB  - COPII vesicle formation requires only three coat assembly subunits: Sar1p,
      Sec13/31p, and Sec23/24p. PI 4-phosphate or PI 4,5-bisphosphate is required for
      the binding of these proteins to liposomes. The GTP-bound form of Sar1p recruits
      Sec23/24p to the liposomes as well as to the ER membranes, and this Sar1p
      Sec23/24p complex is required for the binding of Sec13/31p. Ultrastructural
      analysis shows that the binding of COPII coat proteins to liposomes results in
      coated patches, coated buds, and coated vesicles of 50-90 nm in diameter. Budding
      proceeds without rupture of the donor liposome or vesicle product. These
      observations suggest that the assembly of the COPII coat on the ER occurs by a
      sequential binding of coat proteins to specific lipids and that this assembly
      promotes the budding of COPII-coated vesicles.

PMID- 9568719
TI  - Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to
      the centrosome using a WD40-containing subunit.
AB  - Microtubule disassembly at centrosomes is involved in mitotic spindle function.
      The microtubule-severing protein katanin, a heterodimer of 60 and 80 kDa
      subunits, was previously purified and shown to localize to centrosomes in vivo.
      Here we report the sequences and activities of the katanin subunits. p60 is a new
      member of the AAA family of ATPases, and we show that expressed p60 has
      microtubule-stimulated ATPase and microtubule-severing activities in the absence
      of p80. p80 is a novel protein containing WD40 repeats, which are frequently
      involved in protein-protein interactions. The p80 WD40 domain does not
      participate in p60 dimerization, but localizes to centrosomes in transfected
      mammalian cells. These results indicate katanin's activities are segregated into
      a subunit (p60) that possesses enzymatic activity and a subunit (p80) that
      targets the enzyme to the centrosome.

PMID- 9568720
TI  - NMR structure of the bacteriophage lambda N peptide/boxB RNA complex: recognition
      of a GNRA fold by an arginine-rich motif.
AB  - The structure of the complex formed by the arginine-rich motif of the
      transcriptional antitermination protein N of phage lambda and boxB RNA was
      determined by heteronuclear magnetic resonance spectroscopy. A bent alpha helix
      in N recognizes primarily the shape and negatively charged surface of the boxB
      hairpin through multiple hydrophobic and ionic interactions. The GAAGA boxB loop
      forms a GNRA fold, previously described for tetraloops, which is essential for N
      binding. The fourth nucleotide of the loop extrudes from the GNRA fold to enable
      the E. coli elongation factor NusA to recognize the N protein/RNA complex. This
      structure reveals a new mode of RNA-protein recognition and shows how a small RNA
      element can facilitate a protein-protein interaction and thereby nucleate
      formation of a large ribonucleoprotein complex.

PMID- 9568721
TI  - Interferon-alpha: evolving therapy for AIDS-associated Kaposi's sarcoma.
AB  - This article reviews developments over nearly 15 years in the application of
      interferon-alpha (IFN-alpha) to the treatment of Kaposi's sarcoma (KS) in
      patients with acquired immunodeficiency syndrome (AIDS). The initial success of
      IFN treatment for selected patients with AIDS-associated KS occurred before
      identification of the human immunodeficiency virus (HIV) and in the absence of
      any coherent view of KS pathogenesis. A more comprehensive understanding of the
      biology of both AIDS and KS, together with increased knowledge of the biologic
      effects of IFN and therapeutic advances in the treatment of HIV infection, have
      made IFN therapy for KS both more rational and more successful. There is every
      reason to believe that the current results with IFN for KS can be improved on by
      capitalizing on recent improvements in HIV therapy and the availability of
      specific inhibitors of angiogenic cytokines. I sincerely thank the Milstein
      family and my colleagues in the International Society for Interferon and Cytokine
      Research (ISICR) for recognizing this work, which is the product of many
      collaborations between clinical and basic scientists in my own institution and
      elsewhere.

PMID- 9568722
TI  - IFN-gamma inhibits growth of WISH cells in a cell cycle phase-specific manner.
AB  - Treatment of WISH (human amnion) cells with interferon-gamma (IFN-gamma) inhibits
      their growth. Release of the cells from IFN-gamma-mediated growth inhibition led
      to a rapid and significant increase in DNA synthesis, followed by doubling of
      cell numbers. The DNA synthesis profile was strikingly similar to that shown by
      WISH cells released from growth arrest by the G1/S phase inhibitor, aphidicolin.
      This strongly suggested that IFN-gamma treatment leads to growth inhibition of
      WISH cells at the G1/S boundary of the cell cycle. In contrast, IFN-alpha blocked
      growth of these cells at the G0/G1 boundary.

PMID- 9568723
TI  - Transgenic mice expressing a truncated Peromyscus leucopus TNF-alpha gene
      manifest an arthritis resembling ankylosing spondylitis.
AB  - Several studies have implicated tumor necrosis factor-alpha (TNF-alpha) in
      autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate further the
      role of TNF-alpha in inflammatory arthritis, we generated transgenic mice
      harboring a truncated Peromyscus leucopus TNF-alpha (Pe-TNF) gene. An arthritic
      phenotype closely resembling human ankylosing spondylitis was observed only in
      transgenic lines expressing the Pe-TNF transgene at the mRNA level. We
      characterized the arthritic phenotype in detail by radiographic and histologic
      techniques. It consisted of severe axial skeletal kyphosis and ankylosis,
      accompanied by an inflammatory and fibrotic process at the end plates and
      enthesis. Peripheral joint lesions were absent in mice expressing the P. leucopus
      TNF-alpha gene, in contrast to the RA-like phenotype described in transgenic mice
      expressing a truncated human TNF-alpha gene. The Pe-TNF transgenic mouse model
      provides a unique opportunity to explore potential mechanisms whereby TNF-alpha
      may initiate an autoimmune arthritis resembling ankylosing spondylitis.

PMID- 9568724
TI  - Augmentation of hematopoiesis by fibroblast-mediated interleukin-6 gene therapy
      in mice with chemotherapy.
AB  - Murine fibroblast NIH3T3 cells engineered to secrete interleukin-6 (NIH3T3-IL-6)
      were implanted intraperitoneally into mice and observed for their hematopoietic
      effects with or without 5-fluorouracil (5-FU) administration. In normal mice, the
      platelet and neutrophil counts in peripheral blood increased significantly after
      implantation of NIH3T3-IL-6 cells, but the total white blood cell numbers showed
      no obvious elevation. The granulocyte-macrophage colony-forming unit (CFU-GM) and
      megakaryocyte colony-forming unit (CFU-MK) numbers formed by stem cells in bone
      marrow and spleen were also found to be significantly increased after
      implantation of NIH3T3-IL-6 cells when compared with those in mice after
      implantation of NIH3T3 cells transduced with neomycin gene (NIH3T3-Neo). To
      observe the protective effects of NIH3T3-IL-6 cells on hematopoietic depression
      in chemotherapy-treated mice, the mice were preinjected with 5-FU at a dosage of
      150 mg/kg before implantation of NIH3T3-IL-6 cells. The platelet and neutrophil
      counts showed accelerated recovery after implantation of NIH3T3-IL-6 cells. The
      numbers of CFU-GM and CFU-MK in bone marrow and spleen were also found to be
      markedly increased in hematopoietic-depressed mice when compared with those in
      mice implanted with NIH3T3-Neo cells. These data suggest that fibroblast-mediated
      IL-6 gene therapy, which can augment hematopoiesis in mice with or without
      chemotherapy, will be of great help in the recovery from hematopoietic depression
      after chemotherapy.

PMID- 9568725
TI  - Inhibition of adenylyl cyclase by alpha chemokines IL-8 and GRO-alpha in Chinese
      hamster ovary cells expressing R1 and R2 receptors.
AB  - Interleukin-8 (IL-8) and growth-related oncogene protein-alpha (GRO-alpha) belong
      to a family of alpha chemokines. The biologic effects of IL-8 are realized by
      binding to two seven-transmembrane receptors R1 and R2 and that of GRO-alpha by
      binding to receptor R2. Chinese hamster ovary (CHO) cells stably expressing R1
      and R2 have been used to demonstrate that the ligand-dependent signaling by both
      receptors is via the inhibition of adenylyl cyclase. This inhibition is pertussis
      toxin sensitive and could be mediated by G(alpha)i2, which is present in CHO
      cells. GRO-alpha inhibits adenylyl cyclase exclusively in CHO-R2 cells, and IL-8
      inhibits in both CHO-R1 and CHO-R2 cells. The cAMP status in cells is an easy,
      reliable, quantifiable signal that is amenable to high throughput screening for
      small molecule analogs.

PMID- 9568727
TI  - Effect of IFN-alpha on normal human hematopoiesis: an immunohistochemical and
      morphometric study on trephine biopsy specimens.
AB  - To elucidate the effects of interferon-alpha (IFN-alpha) on normal human bone
      marrow in vivo, an immunomorphometric study was performed using trephine biopsy
      specimens without hematopoietic pathology. Samples were derived from patients
      with mycosis fungoides but no marrow involvement, who were undergoing low-dose
      IFN-alpha treatment. Parameters included density of reticulin (argyrophilic)
      fibers, CD61+ megakaryocytes, PGM1+ macrophages, the GSA-I lectin-expressing
      (activated) macrophage subpopulation, proliferative activity (PCNA staining), and
      apoptosis. Following IFN-alpha therapy (3 x 3 x 10(6) U/week between 6 and 21
      months), morphometric evaluation of sequential bone marrow examinations revealed
      a significant increase in the number of megakaryocytes and the amount of
      reticulin fibers. Additionally, there was an overall decrease in PCNA+ cells,
      accompanied by a reduction in the incidence of apoptotic bodies. On the other
      hand, total number of macrophages and their activated subfraction remained
      unchanged. Opposed to in vitro findings, a fibrogenetic capacity of IFN-alpha
      associated with megakaryocyte growth was detectable. Moreover, contrasting with
      effects of IFN-alpha treatment in chronic myelogenous leukemia, the incidence of
      apoptosis was significantly reduced. This feature was assumed to contribute to a
      maintenance of steady-state hematopoiesis expressed by a nonaltered bone marrow
      cellularity in our specimens.

PMID- 9568726
TI  - Phase II trial of recombinant IFN-alpha2a with etoposide/cisplatin induction and
      interferon/megestrol acetate maintenance in extensive small cell lung cancer.
AB  - Previous data suggested interaction of cisplatin with interferon (IFN) in non
      small cell lung cancer and a possible effect of IFN in maintaining remission in
      small cell lung cancer (SCLC). This study was designed to further examine the
      effect of IFN in the treatment of extensive disease (ED) SCLC. Forty previously
      untreated patients with performance status (PS) of 0-2 (Zubrod scale) were
      treated with etoposide (100 mg/m2 for 3 days), cisplatin (25 mg/m2 for 3 days)
      (EP), and recombinant IFN-alpha2a (rIFN-alpha2a) (5 x 10(6) U/m2 for 3 days) for
      six cycles (induction), followed by rIFN-alpha2a (5 x 10(6) U/m2) thrice weekly
      and megestrol acetate (40 mg q.i.d.) as maintenance therapy for 6 months or until
      progressive disease or intolerable toxicity was documented. Patients were 25 men
      (62%) and 15 women (38%), median age 58 (28-76), median Zubrod performance status
      1 (0-2). Major sites of metastasis include liver (55%), bone (42%), bone marrow
      (25%), and adrenal gland (18%). Of 40 eligible patients accrued to this trial, 35
      were evaluable for response, and 37 were evaluable for toxicity. There were 3
      complete and 28 partial responses, for an overall response rate of 89%. With 39
      of 40 patients followed until death, median survival (Kaplan-Meier) is estimated
      at 46 weeks (95% CI range 35-55). Twenty patients completed six cycles of
      induction, and 16 received maintenance therapy, median 2 cycles (range 1-3).
      Major toxicity during induction included grade 4 granulocytopenia in 24%, grade 2
      3 nausea or vomiting or both in 41%, grade 2 fatigue in 24%, grade 2 anorexia in
      22%, and grade 2-3 renal insufficiency in 9% of 175 total courses of chemotherapy
      administered. Toxicity during the maintenance phase was notable for grade 2-3
      fatigue in 43%, grade 2-3 anorexia in 24%, grade 2-3 weight loss in 10%, and
      grade 3-4 anemia in 17% of 30 courses. There were no treatment-related deaths.
      The addition of rIFN-alpha2a to EP in induction chemotherapy of ED SCLC, followed
      by rIFN-alpha2a and megestrol acetate maintenance therapy, was reasonably well
      tolerated. The complete and overall response rates and duration of remission and
      survival appear to be similar to those generally obtained with EP alone in
      similar patients.

PMID- 9568728
TI  - Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of
      xerostomia in patients with Sjogren's syndrome.
AB  - A single-blinded controlled trial was conducted to test the efficacy of low-dose
      oral human interferon-alpha (IFN-alpha) to improve salivary function in patients
      with Sjogren's syndrome. Fifty-six outpatients with primary and 4 patients with
      secondary Sjogren's syndrome were assigned randomly into treatment groups of
      either IFN-alpha or sucralfate (control). The IFN-alpha (150 IU) or sucralfate
      (250 mg) was given orally three times a day for 6 months. Saliva was quantitated
      monthly by the Saxon test. After 6 months of treatment, 15 of 30 (50%) IFN-alpha
      treated patients had saliva production increases at least 100% above baseline,
      whereas only 1 of 30 (3.3%) sucralfate patients had a comparable increase (p <
      0.001). The increase in saliva production, by treatment group, was significantly
      greater (p < 0.01) in the IFN-alpha treated group at every month after treatment.
      Serial labial salivary gland biopsies of 9 IFN-alpha responder patients showed
      that lymphocytic infiltration was significantly decreased (p < 0.02) and the
      proportion of intact salivary gland tissue was significantly increased (p =
      0.004) after the IFN-alpha treatment. In this study, IFN-alpha therapy
      significantly improved Sjogren's syndrome salivary gland dysfunction.

PMID- 9568729
TI  - IFN-gamma primes macrophage responses to bacterial DNA.
AB  - Macrophages recognize and are activated by unmethylated CpG motifs in bacterial
      DNA. Here we demonstrate that production of nitric oxide (NO) from murine RAW 264
      macrophages and bone marrow-derived macrophages (BMM) in response to bacterial
      DNA is absolutely dependent on interferon-gamma (IFN-gamma) priming. Similarly,
      arginine uptake and expression of the inducible nitric oxide synthase (iNOS) gene
      in response to bacterial DNA in BMM occurred only after IFN-gamma priming. In
      contrast, mRNA for the cationic amino acid transporter, CAT2, was induced by
      plasmid DNA alone, and priming with IFN-gamma had no effect on this response.
      Tumor necrosis factor-alpha (TNF-alpha) release from RAW 264 and BMM in response
      to bacterial DNA was augmented by IFN-gamma pretreatment. In a stably transfected
      HIV-1 long terminal repeat (LTR) luciferase RAW 264 cell line, IFN-gamma and
      bacterial DNA synergized in activation of the HIV-1 LTR. Bacterial DNA has been
      shown to induce IFN-gamma production in vivo as an indirect consequence of
      interleukin-12 (IL-12) and TNF-alpha production from macrophages. The results
      herein suggest the existence of a self-amplifying loop that may have implications
      for therapeutic applications of bacterial DNA.

PMID- 9568730
TI  - Prolonged allograft survival in cynomolgus monkeys treated with a monoclonal
      antibody to the human type I interferon receptor and low doses of cyclosporine.
AB  - A monoclonal antibody (mAb) directed against the extracellular domain of the
      IFNAR1 chain of the human interferon-alpha (IFN-alpha) receptor (IFN-alphaR),
      which inhibits activation of the Jak-Stat signal transduction pathway,
      administered together with a subeffective dose of cyclosporine induced prolonged
      survival of skin allografts in major histocompatibility complex (MHC) divergent
      cynomolgus monkeys. Skin biopsies from animals treated with anti-IFN-alphaR mAb
      and cyclosporine revealed very low levels of MHC class I and class II antigen
      expression and the absence of histologic signs of rejection. Monkey antibodies
      (IgG) to the mouse antihuman IFN-alphaR mAb were not detected in the serum of any
      of the animals treated with the anti-IFN-alphaR mAb either alone or together with
      cyclosporine. The anti-IFN-alphaR mAb abrogated activation of the Jak-Stat signal
      transduction pathway in IFN-treated cells. These results, which show that
      selective and long-lasting immunosuppression can be obtained by short-term
      administration of an IFN-alpha antagonist together with a subeffective dose of
      cyclosporine, may have important implications for the therapy of human allograft
      rejection.

PMID- 9568731
TI  - Transgenic mouse models to study the role of APOE in hyperlipidemia and
      atherosclerosis.
AB  - Transgenic technologies have provided a series of very useful mouse models to
      study hyperlipidemia and atherosclerosis. Normally, mice carry cholesterol mainly
      in the high density lipoprotein (HDL) sized lipoproteins, and have low density
      lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol levels.
      These low LDL and VLDL levels are due to the very rapid metabolism of remnant
      clearance in mice, which hamper metabolic studies. In addition, due to the lack
      of atherogenic lipoproteins, mice will not readily develop atherosclerosis. This
      situation has changed completely, because to date, most known genes in
      lipoprotein metabolism have been used in transgenesis to obtain mice in which
      genes have been silenced or overexpressed. These experiments have yielded many
      mouse strains with high plasma lipid levels and a greater susceptibility for
      developing atherosclerosis. One of the most widely used strains are knock-out
      mice deficient for apoE, which is one of the central players in VLDL metabolism.
      Subsequently, a wide variety of other transgenic studies involving APOE have been
      performed elucidating the role of apoE and apoE mutants in lipolysis, remnant
      clearance, cellular cholesterol efflux and atherogenesis. In addition, the APOE
      mouse models are excellent tools for the development of gene therapy for
      hyperlipidemias.

PMID- 9568732
TI  - Probucol treatment attenuates the aortic atherosclerosis in Watanabe heritable
      hyperlipidemic rabbits.
AB  - We examined the effect of probucol on the aortic atherosclerosis already
      developed in Watanabe heritable hyperlipidemic (WHHL) rabbits at the initiation
      of treatment. In WHHL rabbits treated with probucol for 5 months from 8 months
      old, the lesion area in the aorta was significantly (P < 0.05) reduced when
      compared with that in untreated animals as well as animals at age 8 months. In
      contrast, plasma cholesterol levels in the probucol-treated group and untreated
      group during the experiment were not significantly different. LDL prepared from
      rabbits receiving probucol for 5 months showed resistance to oxidation by copper
      ions. Plasma CETP activity was significantly (P < 0.05) increased by probucol
      treatment. An immunohistochemical study showed that macrophages were abundant in
      the atherosclerotic lesions of untreated rabbits whereas smooth muscle cells were
      predominant in lesions of probucol-treated rabbits. These results suggest that
      the atherosclerotic lesion in WHHL rabbits can regress when treated by probucol
      and that the attenuation of atherosclerosis in this animal involves effects of
      probucol other than a decrease in plasma cholesterol, for example anti-oxidant
      activity.

PMID- 9568733
TI  - Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are
      independent risk factors for coronary heart disease in Japanese: a case-control
      study.
AB  - A missense variant of the C677T (Ala --> Val) polymorphism in the
      methylenetetrahydrofolate reductase gene (MTHFR) (the T allele) may increase
      levels of plasma homocysteine. Apolipoprotein E4 increases plasma LDL-cholesterol
      levels. Increased levels of homocysteine and LDL-cholesterol have been recognized
      as risk factors for coronary heart disease (CHD). To examine whether the
      polymorphisms in the MTHFR gene and the APOE gene are associated with CHD in the
      Japanese, we analyzed 214 CHD patients with an onset age before 65 and 310
      apparently healthy persons. In the controls, significantly higher plasma
      concentrations of homocysteine were observed in the MTHFR TT genotype (15.1+/-6.0
      mmol/l) compared with the CT genotype (11.2+/-1.9 mmol/l) and the CC genotype
      (10.5+/-3.3 mmol/l). The MTHFR TT genotype was significantly more frequent in the
      CHD patients (28.5%) compared with the control subjects (13.5%); the odds ratio
      was 2.54 (P < 0.00003). Subjects with the apo E4 allele were significantly more
      frequent in the CHD group (22.9%) than in the control group (10.0%); the odds
      ratio was 2.74 (P < 0.00004). Multivariate analysis showed that the TT genotype
      of MTHFR and the apoE4 allele are independent risk factors for CHD in the
      Japanese.

PMID- 9568734
TI  - Effect of dietary catechin and vitamin E on aortic fatty streak accumulation in
      hypercholesterolemic hamsters.
AB  - Male golden Syrian hamsters were fed for 16 weeks on a hypercholesterolemic diet
      containing, per kg, 150 g of lipids (90 g butterfat, 35 g vitamin E-stripped corn
      oil and 25 g fish oil), 2 g cholesterol and either 3 IU vitamin E (3 IU E), 3 IU
      vitamin E and 200 mg catechin hydrate (3 IU E-200 Cat) or 30 IU vitamin E (30 IU
      E). More fatty streaks, measured by Oil Red O staining, were deposited in aortas
      of hamsters fed 3 IU E than in those fed either 3 IU E-200 Cat or 30 IU E. Lipid
      staining increased with plasma low-density lipoprotein cholesterol (LDL-C) in all
      animals. At the same concentration of LDL-C, animals fed either 3 IU E-200 Cat or
      30 IU E developed less fatty streaks than those fed 3 IU E. Plasma LDL-C and
      total cholesterol were highest in hamsters fed 3 IU E and LDL-C and total
      cholesterol in animals fed 3 IU-200 Cat were not different from those fed either
      3 IU E or 30 IU E. This study showed the importance of circulating plasma LDL-C
      on atherogenesis and the inhibitory effect on this process of both dietary
      vitamin E and catechin.

PMID- 9568735
TI  - Postprandial responses of plasma lipids and lipoproteins in subjects with apoA
      I(Lys107-->0).
AB  - Subjects with apoA-I(Lys107-->0) deletion mutation have reduced levels of plasma
      HDL cholesterol, apoA-I, apoA-II and Lp(AI:AII). In the present study were
      describe the postprandial responses of apoA-I(Lys107-->0) subjects (n=6) to the
      ingestion of a fat rich meal compared to the responses of their unaffected family
      members (n=6). The postprandial plasma triglyceride responses were comparable in
      the two groups of subjects. Plasma postprandial HDL cholesterol levels fell in
      both groups; patients (0.89+/-0.05-0.76+/-0.06 mmol/l, P=0.0032) and control
      subjects (1.32+/-0.25-1.18+/-0.21 mmol/l; P=0.0022). HDL2 cholesterol levels
      tended to rise, but the changes were not significant. By contrast, in both
      patients and control subjects, the HDL3 cholesterol levels fell; patients (0.52+/
      0.15-0.37+/-0.11 mmol/l, P=0.0068) and control subjects (0.63+/-0.10-0.49+/-0.08
      mmol/l, P=0.0078), respectively. In both patients and control subjects the plasma
      HDL2 mass increased in response to the fat meal; patients (94.7+/-37.3-114.3+/
      28.8 mg/dl, P=0.0397) and control subjects (142.1+/-32.8-168.1+/-29.8 mg/dl,
      P=0.0298), whereas HDL3 mass decreased; patients (162.3+/-36.8-131.4+/-28.9
      mg/dl, P=0.0251) and control subjects (185.5+/-34.1-161.1+/-29.0 mg/dl,
      P=0.0021), respectively. In control subjects the triglyceride levels increased in
      both HDL2 (0.10+/-0.06-0.17+/-0.06 mmol/l; P=0.0005) and to a lesser extent in
      HDL3 (0.10+/-0.03-0.12+/-0.02 mmol/l, P=0.0017). In patients, triglyceride levels
      in both HDL subclasses remained unchanged. Changes in the concentration of Lp(AI)
      in HDL2 and HDL3 were comparable in the two groups of subjects. The Lp(AI:AII)
      concentration in HDL2 remained unchanged in the patients, but increased in
      control subjects (change+27%. P=0.0026). Consequently, the 20% difference at
      baseline in the concentration of Lp(AI:AII) in HDL2 between the patients and
      control subjects increased postprandially to 45% (P=0.0240). The Lp(AI:AII)
      concentration in HDL3 decreased in both groups, but the changes were non
      significant. Our findings show that in postprandial state, no accumulation of
      triglycerides in HDL subclasses occurs in patients with apoA-I(Lys[107]-->0) and
      that these patients appear to lack the ability to respond to fat feeding by
      increasing the Lp(AI:AII) concentration in HDL2.

PMID- 9568736
TI  - The antioxidative effects of the isoflavan glabridin on endogenous constituents
      of LDL during its oxidation.
AB  - The effect of the consumption of glabridin, an isoflavan isolated from
      Glycyrrhiza glabra (licorice) root, on the susceptibility of low density
      lipoprotein (LDL) to oxidation was studied in atherosclerotic apolipoprotein E
      deficient (E[o] mice) and was compared with that of the known flavonoids,
      quercetin and catechin. Glabridin inhibitory activity on in vitro oxidation of
      human LDL was also investigated by determining the formation of lipid peroxides
      and oxysterols and the consumption of LDL-associated lipophilic antioxidants.
      Determination of the extent of LDL oxidation by measuring the formation of
      thiobabituric acid reactive substances (TBARS) after 2 h of LDL incubation with
      CuSO4 (10 microM) or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) (5
      mM), revealed that glabridin or quercetin consumption resulted in a 53 and 54%
      reduction in copper ion induced oxidation, respectively, and a 95 and 83%
      reduction in AAPH induced LDL oxidation, respectively. No inhibition was obtained
      with consumption of catechin. About 80% of glabridin was found to bind to the LDL
      human particle. In the in vitro oxidation of LDL induced by AAPH (5 mM),
      glabridin inhibited the formation of TBARS, lipid peroxides and cholesteryl
      linoleate hydroperoxide (CLOOH) at all the concentrations tested (5-60 microM),
      while in oxidation induced by copper ions (10 microM), glabridin exhibited a pro
      oxidant activity at concentrations lower than 20 microM, and a clear antioxidant
      activity at concentrations greater than 20 microM. Glabridin (30 microM)
      inhibited the formation of cholest-5-ene-3,7-diol (7-hydroxycholesterol), cholest
      5-ene-3-ol-7-one (7-ketocholesterol) and cholestan-5,6-epoxy-3-ol (5,6
      epoxycholesterol) after 6 h of AAPH induced LDL oxidation, by 55, 80 and 40%,
      respectively, and after 6 h of copper ion induced LDL oxidation, by 73, 94 and
      52%, respectively. Glabridin also inhibited the consumption of beta-carotene and
      lycopene by 38 and 52%, respectively, after 0.5 h of LDL oxidation with AAPH, but
      failed to protect vitamin E. The in vivo and in vitro reduction of the
      susceptibility of LDL to oxidation obtained with glabridin, may be related to the
      absorption or binding of glabridin to the LDL particle and subsequent protection
      of LDL from oxidation by inhibiting the formation of lipid peroxides and
      oxysterols, and by protecting LDL associated carotenoids.

PMID- 9568737
TI  - Changes in distribution of glycosaminoglycans during the progression of
      cholesterol induced atherosclerosis in Japanese quail.
AB  - The temporal and spatial distribution and relative concentration of the
      proteoglycan glycosaminoglycan component were studied during the progression of
      atherosclerosis in the systemic arteries of Japanese quail selected for
      cholesterol induced atherosclerosis (CIA). The CIA quail were placed on either
      control or 0.5% added cholesterol diets at 3 months of age. The major systemic
      arteries (dorsal aorta, right and left brachiocephalic) were collected at 1- or 2
      week intervals over the 10-week period of cholesterol feeding. In the cholesterol
      fed quail, alcian blue staining of the dorsal aorta showed elevations of
      glycosaminoglycans in regions of the artery with atherosclerotic plaque,
      beginning at the 6-week time point. By biochemical analysis, increases in
      glycosaminoglycan relative concentration was detected at the 10-week time point.
      In addition to the change in glycosaminoglycan relative concentration and
      distribution, the cholesterol fed animals also formed foam cells characteristic
      of atherosclerotic plaques. Therefore, the conclusion reached was that the CIA
      line of Japanese quail is a valid animal model for the study of alterations in
      proteoglycan metabolism in atherosclerotic plaques induced by
      hypercholesterolemia.

PMID- 9568738
TI  - Delapril slows the progression of atherosclerosis and maintains endothelial
      function in cholesterol-fed rabbits.
AB  - The renin-angiotensin system is an important modulator of arterial blood pressure
      and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently
      used in the treatment of hypertension. The pleiotropic actions exerted by
      angiotensin II (AngII) on the functionality of the vessel wall may have pro
      atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is
      has been presented and an antioxidant effect has been attributed to thiol
      containing ACE-Is, like Captopril. The present study has been undertaken to
      investigate the effect of Delapril, a lipophilic ACE-I, on the development of
      atherosclerosis in cholesterol-fed rabbits. While it did not correct
      hyperlipidemia, Delapril dose dependently inhibited the development of
      atherosclerosis, expressed as aortic area covered by lesions (23.3+/-4.1, 21.3+/
      2.4 and 18.5+/-3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg,
      respectively, versus 38.2%+/-6.4 for control animals) and its effect was similar
      to that of Captopril (14.5+/-5.1% at the daily dose of 25 mg/kg). Furthermore,
      Delapril partially and dose dependently restored endothelium-dependent
      relaxation, which is impaired in vessels from hypercholesterolemic animals
      (51.80+/-12.18, 59.74+/-5.16, 69.13+/-8.70 maximal percent relaxation versus
      48.26+/-3.05% for the untreated control and 67.67+/-6.72% for Captopril-treated
      animals). An antioxidant mechanism is unlikely to explain this data, since
      Delapril does not contain thiol groups. These observations suggest that Delapril
      may represent an effective pharmacological approach for the treatment of
      atherosclerosis during its early phases.

PMID- 9568739
TI  - The ACAT inhibitor, CI-1011 is effective in the prevention and regression of
      aortic fatty streak area in hamsters.
AB  - The hypocholesterolemic and anti-atherogenic properties of sulfamic acid ((2,4,6
      tris (1-methylethyl) phenyl) acetyl) 2,6-bis(1-methylethyl) phenyl ester, the
      ACAT inhibitor, CI-1011, was tested in 120 male F1B hamsters fed a
      hypercholesterolemic chow-based diet containing 10%, coconut oil and 0.05%
      cholesterol plus: (i) no drug treatment (HCD); (ii) 3 mg/kg per day (HCD+3):
      (iii)10 mg/kg per day (HCD+10); (iv) 30 mg/kg per day (HCD+30) of CI-1011; or (v)
      500 mg/kg per day of cholestyramine (CSTY). Plasma samples were collected at 8
      and 10 weeks for measurement of total cholesterol (TC), very low-density
      lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C),
      high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). For the
      progression studies, animals were euthanized after 10 weeks for aortic fatty
      streak area and hepatic cholesterol analysis. For the regression study, a cohort
      of the HCD was treated with 30 mg/kg per day of CI-1011 (regression) for an
      additional 8 weeks. The HCD+3, HCD+10, HCD+30 and CSTY lowered plasma TC (25, 32,
      34 and 32%, respectively), VLDL-C (62, 74, 71 and 75%, respectively), LDL-C (25,
      38, 47 and 46%, respectively) and TG (48, 47, 42 and 45%, respectively). All
      treatments resulted in a significant lowering of aortic fatty streak area (68,
      86, 93 and 94%, respectively) and reduction in hepatic cholesteryl esters (57,
      65, 67 and 70%, respectively). Regression of aortic fatty streak area was 90%
      after 8 weeks of HCD+30 treatment. Also during the regression phase, plasma TC,
      LDL-C and TG were lowered 23, 33 and 47%, respectively, as well as, hepatic
      cholesteryl esters (76%). Significant correlations between plasma LDL-C
      concentration and aortic fatty streak area (r=0.62, P < 0.004) in the HCD+10
      group, suggest that CI-1101 altered aortic lipid infiltration primarily by its
      effect on plasma lipids. However the 30 mg/kg per day dose of CI-1011 which
      additionally reduced aortic fatty streak area by 51% relative to the 10 mg/kg per
      day dose was only associated with a 14% further decrease in plasma LDL-C. Finally
      the 10-fold regression of aortic fatty streak area was associated with only a 35%
      reduction in plasma LDL-C. These exceptions to the lipid-lesion relationship
      raise the possibility of additional effects of CI-1011, which may occur
      independent of or in concert with lipoprotein cholesterol lowering. It is
      concluded that in hypercholesterolemic hamsters, CI-1011 is approximately 50
      times more potent than cholestyramine in cholesterol-lowering, reduction and
      regression of aortic fatty streak area.

PMID- 9568740
TI  - Human cardiac microvascular and macrovascular endothelial cells respond
      differently to oxidatively modified LDL.
AB  - Oxidation of low density lipoproteins (LDL) is considered a key event in the
      pathogenesis of atherosclerotic lesions. Disturbed generation of coagulatory and
      anticoagulatory factors by endothelial cells contributes to thrombosis and the
      progression of atherosclerosis in coronary arteries. In this study, the effects
      of native LDL (n-LDL) and oxidized LDL (ox-LDL) on human coronary endothelial
      cells were measured. The reaction of coronary endothelial cells to LDL were
      compared with those of cardiac microvascular endothelial cells grown under
      comparable conditions. LDL was isolated by ultracentrifugation and copper
      oxidized. The degree of oxidation was expressed as malondialdehyd (MDA)
      equivalents and was 0.78+/-0.14 nM MDA/mg LDL for native LDL and 13.63+/-1.18
      nmol MDA/mg LDL for ox-LDL. Basal secretion of t-PA and PAI-1 activity were
      higher in macrovascular endothelial cells. Incubation of n-LDL in concentrations
      ranging from 3 to 100 microM/ml LDL-protein did not change t-PA-secretion, PAI-1
      activity or procoagulant activity in both cell types. Ox-LDL (3 to 100 microM/ml
      LDL protein) decreased t-PA secretion in a concentration dependent manner from
      30.9+/-1.7 to 13.7+/-30 ng/ml per 24 h per 10(6) cells (P < 0.01), increased PAI
      1 antigen from 2772+/-587 to 4441+/-766 ng/ml per 24 h per 10(6) cells (P < 0.05)
      as well as PAI-1 activity from 34+/-6 to 55+/-9 AU/ml per 24 h per 10(6) cells (P
      < 0.05) in macrovascular endothelial cells but had only minor effects on
      microvascular endothelial cells. Procoagulant activity measured as coagulation
      time, similarly increased only in macrovascular endothelial cells from 197+/-6 to
      76+/-6 s/24 h per 10(6) cells (P < 0.05). The effect on PAI-1 secretion showed a
      dependency to the degree of oxidation and could be completely blocked by the
      antioxidant probucol. The angiotensin converting enzyme (ACE), which represents
      an endothelial enzyme not related to coagulation, remained unchanged during
      incubation with ox-LDL. Basal ACE activity was higher in microvascular
      endothelial cells. The higher susceptibility of macrovascular endothelial cells
      to ox-LDL may partially determine the localization of thrombus formation and the
      development of atherosclerotic plaques in hyperlipidemic patients.

PMID- 9568741
TI  - Relationship between bioavailability and hypocholesterolemic activity of YM17E,
      an inhibitor of ACAT, in cholesterol-fed rats.
AB  - The relationship between bioavailability and the serum cholesterol-lowering
      effect of YM17E, an ACAT inhibitor was investigated. Serum cholesterol levels in
      cholesterol-fed rats decreased after both oral and intravenous administration of
      YM17E. Marked inhibition of cholesterol absorption was observed after oral
      administration, but not after intravenous administration. YM17E and its five
      active metabolites were primarily distributed in the liver after intravenous
      administration, but in small intestine and liver after oral administration.
      Hepatic ACAT activity in cholesterol-fed rats was inhibited by intravenous
      administration. Cholesteryl ester input into plasma by Triton WR-1339 treatment
      to the rats was inhibited by intravenous administration of YM17E. Plasma
      clearance of 125I-LDL in cholesterol-fed rats increased after YM17E treatment
      suggesting a decrease in LDL production. These results indicate that the
      hypocholesterolemic effect of intravenous YM17E was due to hepatic ACAT
      inhibition, not an inhibition of intestinal cholesterol absorption. The
      contribution of ACAT inhibition in small intestine and liver on the
      pharmacological effect could be explained by plasma inhibitor concentration after
      oral or intravenous administration of YM17E. From these results, it is concluded
      that the change in bioavailability of ACAT inhibitors change the mechanism of
      hypocholesterolemic effects, shifting the relative contributions of small
      intestinal and hepatic ACAT inhibition.

PMID- 9568742
TI  - Alimentary lipemia enhances the membrane expression of platelet P-selectin
      without affecting other markers of platelet activation.
AB  - The present study was conducted to determine whether alimentary lipemia alters
      platelet activity in vivo. Normolipidemic volunteers were given a fatty meal and
      platelet function was assessed before, and 3 and 6 h after the meal. Platelet
      aggregability and secretion was determined using whole blood flow cytometry
      (expression of platelet P-selectin and fibrinogen binding), filtragometry ex vivo
      (reflecting platelet aggregability in vivo) and by measurements of platelet
      specific products in plasma (beta-thromboglobulin and platelet factor 4). Plasma
      triglycerides increased from 0.8 (0.6:1.1; median, 25th and 75th percentiles) to
      1.7 (1.0:2.3) mmol/l at 3 h and returned to baseline after 6 h (P < 0.001, one
      way ANOVA). Apo B-100 and apo B-48 were both markedly increased 3 h
      postprandially in the Sf 60-400 fraction (large VLDLs, P < 0.001 for both),
      whereas the Sf 20-60 (small VLDLs) and Sf 12-20 fractions (IDL) did not change.
      The platelet function assessments revealed that the percentage of platelets
      expressing P-selectin increased by 40% (5%; 64%) after 3 h and by 51% (- 7%; 85%)
      6 h postprandially in unstimulated samples (P < 0.05 for both). In samples
      stimulated by ADP in vitro P-selectin expression increased by 45% (6%; 58%) after
      3 h and by 30% (12%; 58%) (P<0.01 for both) after 6 h at 0.1 microM. Platelet P
      selectin expression was less influenced at higher ADP concentrations. The plasma
      levels of beta-thromboglobulin (approximately 20 ng/ml) and platelet factor 4
      (approximately 0.3 ng/ml) were not affected by the fat load. Flow cytometric
      analyses of fibrinogen binding and filtragometry measurements also failed to
      reveal any postprandial alterations. The present finding of enhanced platelet P
      selectin expression suggests that platelets are mildly sensitized postprandially.
      Whether this is of importance for thrombus formation and atherosclerosis needs to
      be studied further.

PMID- 9568743
TI  - Effect of infusion of a triacylglycerol emulsion on low-density lipoprotein
      composition and oxidizability.
AB  - Six, healthy, male volunteers aged 19-48 years received a 4-h infusion of a
      triacylgycerol emulsion (Intralipid 10%) after an overnight fast. Plasma
      triacylglycerol (TAG) and low-density lipoprotein (LDL) -TAG, -protein and 
      phospholipid concentrations all rose significantly during the course of the
      infusion and remained elevated 90 min after its end. The weight/weight ratio of
      LDL-TAG to -protein also increased significantly (from 0.43+/-0.14 to 0.79+/-0.30
      at 4 h and 0.63+/-0.31 90 min later), indicating TAG-enrichment of LDL particles.
      There were no significant changes in LDL particle density. Susceptibility of LDL
      to copper-induced oxidation, as measured by the lag time for conjugated diene
      formation, was less at the end of and 90 min after the end of the infusion than
      in the fasting state (59.3+/-16.5, 47.4+/-17.4 and 34.8+/-19.6 min,
      respectively). Lag time was positively correlated with LDL TAG in the fasting
      state (rS=0.900, P < 0.0001) and the correlation continued with the post-infusion
      TAG-enriched LDL (rs=0.886, P < 0.05). Acute hypertriglyceridaemia induced by
      infusion of Intralipid therefore causes TAG-enrichment and a decrease in the
      susceptibility to oxidation of LDL. TAG-enrichment of LDL may lead to subsequent
      potentially atherogenic changes in LDL following TAG hydrolysis.

PMID- 9568744
TI  - Hypobetalipoproteinemia associated with apo B-48.4, a truncated protein only 14
      amino acids longer than apo B-48.
AB  - Familial hypobetalipoproteinemia is an autosomal codominant trait that can be
      caused by mutations in the apo B gene. Here we report a novel apo B gene mutation
      causing hypobetalipoproteinemia, that is associated with the synthesis of a
      truncated apo B protein in a young healthy male subject and his mother. The
      mutation is an A deletion at position 6627 of the apo B cDNA leading to a
      truncated protein of 2166 amino acids (apo B-48.4). This truncated apo B was
      detected mainly in VLDL, LDL and in trace amounts in HDL, but not in the
      lipoprotein deficient plasma fraction. Affected family members present with
      elevated levels of HDL-cholesterol, mainly due to an increase in HDL2 particles.
      Postprandial triglycerides and retinyl esters in the d < 1.006 g/ml lipoprotein
      in the proband showed a normal response to an oral fat load compared to a group
      of eight matched healthy controls. In summary this novel mutation is associated
      with hypobetalipoproteinemia with a normal fat absorption as expected for a
      protein with a length similar to that of apo B-48.

PMID- 9568746
TI  - In vitro cytotoxicity of IgG antibodies on vascular endothelial cells from
      patients with endemic peripheral vascular disease in Taiwan.
AB  - A unique peripheral vascular disorder called 'blackfoot disease' is endemic in a
      limited area on the south-west coast of Taiwan. Clinically, the signs and
      symptoms of blackfoot disease (BFD) are similar to those of arteriosclerosis and
      Buerger's disease. A destruction of vascular endothelial cells (ECs) takes place
      at an early stage in the affected limbs. Currently, the cause of BFD is believed
      to be artesian drinking water containing a high concentration of arsenic and/or
      humic substances, although the mechanism of EC destruction is not entirely
      understood. The purpose of the present study was to examine the factors related
      to EC damage in BFD. Thus, we investigated the effects of purified IgG collected
      from patients with BFD (BFD-IgG) and from normal controls (N-IgG) on cultured EC.
      We found that: (1) EC binding activity of BFD-IgG was significantly higher than
      that of N-IgG; (2) BFD-IgG, at a concentration higher than 100 microg/ml but not
      N-IgG, induced concentration-dependent EC cytotoxicity; (3) BFD-IgG at a
      concentration of 100 microg/ml stimulated neither the release of von Willebrand
      factor nor the expression of intercellular adhesion molecule-1 by EC. Fluorescent
      video microscopic examination revealed an increase in transcapillary and
      interstitial diffusion of nailfold capillary loops in clinically normal fingers
      of BFD patients. These findings strongly suggested that immunological mechanisms
      played a significant role in the pathogenesis of BFD. We propose that only
      persons who produce the IgG anti-endothelial cell antibody are potential victims
      of BFD.

PMID- 9568745
TI  - Cardiovascular disease, fibrinogen and the acute phase response: associations
      with lipids and blood pressure in patients with chronic renal disease.
AB  - BACKGROUND: Fibrinogen, an acute phase reactant and coagulation factor is a major
      independent risk factor for cardiovascular disease (CVD) in the general
      population and may interact with lipids to promote CVD risk. METHODS: Plasma
      fibrinogen, lipids and interleukin-6 were measured in 126 patients with chronic
      renal disease (low proteinuria (LP) and high proteinuria (HP) groups) or on
      maintenance dialysis (haemodialysis (HD) or continuous ambulatory peritoneal
      dialysis (CAPD)) and 31 healthy controls (N). RESULTS: Fibrinogen was increased
      in all patients, and by each treatment category, when compared with the control
      group (421+/-143 all, 361+/-72 HD, 429+/-91 CAPD, 395+/-102 LP, 490+/-220 HP vs.
      268+/-54 (N) mg/dl; P=0.0001) and correlated with urinary protein concentration,
      diastolic blood pressure and inversely with albumin. Interleukin-6, the mediator
      of the acute phase response, was increased in the combined patient group (3.2 vs.
      1.5, median, pg/ml, P=.0002) and correlated with fibrinogen (r=0.32, P=0.01) and
      inversely with HDL-cholesterol (r=0.39, P < 0.01), consistent with a persistent
      inflammatory response. Patients with CVD complications (CVD +, n=46) were older,
      had an increased total:HDL-cholesterol ratio (7.7+/-4.3 CVD + vs. 5.9+/-1.8 CVD 
      , P < 0.005), but fibrinogen did not significantly differ (450+/-172 CVD + vs.
      404+/-121 CVD -, P=0.09). Multiple logistic regression analysis identified
      categorisation of patients by values of fibrinogen and the total:HDL-cholesterol
      ratio greater than 95%, of the values for the controls as the only significant
      independent predictor of CVD complications. (Odds ratio for CVD complications of
      13.5 (95%, CI 3.5-52) fibrinogen > 374 and total:HDL-cholesterol > 6.9 versus
      fibrinogen < 374 and total:HDL-cholesterol < 6.9). CONCLUSIONS: The significant
      increase in fibrinogen in all renal disease states was associated with evidence
      of an acute phase response, protein losing states and hypertension. Persistence
      of an acute phase response was also correlated with an adverse lipid profile.
      Fibrinogen alone was a weak discriminator of prevalent CVD disease but in
      conjunction with an increased total:HDL-cholesterol ratio, was associated with
      the prevalence of CVD complications. Hypertension and a persistent acute phase
      response in patients with renal disease could contribute to CVD risk by effects
      upon fibrinogen and lipids, but requires confirmation by prospective evaluation.

PMID- 9568748
TI  - Relationship between glycosylated hemoglobin, blood pressure, serum lipid
      profiles and body fat distribution in healthy Chinese.
AB  - Obesity-related metabolic disorders have not been adequately addressed due to a
      failure to distinguish the importance of general obesity or body fat distribution
      in relation to atherosclerotic risk factors, especially in the less obese
      populations. To assess the relationship between general obesity (reflected by
      BMI, total body fat percentage and total adiposity), body fat distribution
      (reflected by WHR, default regions and ROIs of DEXA) and atherosclerotic risk
      factors in the Chinese population, a total of 872 healthy subjects (477 male and
      395 female) were enrolled in the study. The results indicated that the android
      pattern of fat distribution, independent of general obesity, was positively
      correlated with blood pressure, atherogenic indices, fasting and OGTT 2-h plasma
      glucose, glycosylated hemoglobin (HbA1c), serum concentration of cholesterol,
      triglyceride, LDL cholesterol and negatively correlated with HDL cholesterol in
      both genders. The gender differences in patterns of body fat distribution and
      atherosclerotic risk factors remained significant after adjustments were made for
      age, BMI and total adiposity, although diminished after further adjustments for
      body fat distribution. In conclusion, body fat distribution, rather than general
      obesity, is more correlated with obesity-related atherosclerotic risk factors and
      sex-associated differences. ROIs measured by DEXA may be a useful method to
      evaluate sex-associated changes in body fat distribution and atherosclerotic risk
      factors in the healthy Chinese population.

PMID- 9568747
TI  - Venous endothelial changes in therapeutic arteriovenous fistulae.
AB  - Specimens of veins of therapeutic arteriovenous fistulae from five patients were
      examined by an en face immunohistochemical technique to investigate endothelial
      morphology and the presence of the vasoactive peptide endothelin-1 (ET-1). These
      were compared with control segments of long saphenous veins from six patients.
      Venous endothelium from the arteriovenous shunts was mostly intact even overlying
      phlebosclerotic plaques. Occasional small areas of denudation, with associated
      platelets, were present in the depressions of 'jet' lesion however. The
      endothelial cells were generally elongated and interspersed with foci of
      polyhedral cells. The control saphenous veins contained elongated endothelial
      cells without detectable denudation. Image analysis of histological sections of
      veins from the shunts indicated significantly less intact elastic tissue than
      control veins but greater mononucleated endothelial cell density in en face
      preparations. ET-1 staining was considerably stronger in endothelium from the
      fistulae than in the control saphenous veins and was most intense over the raised
      crescentic ridges of jet lesions, stenoses and phlebosclerotic plaques.
      Endothelial mitoses and cells with hyperchromatic nuclei stained more strongly
      for ET-1 than surrounding cells. These results indicate that the endothelial
      cells lining veins associated with arteriovenous fistulae are dynamically altered
      by the increased haemodynamic stresses associated with these shunts. Furthermore
      ET-1 may act as a localising factor associated with intimal thickening at sites
      of 'jet' lesions, stenosis and phlebosclerosis.

PMID- 9568749
TI  - Influence of polymorphism Q3405E and mutation A3371V in the apolipoprotein B gene
      on LDL receptor binding.
AB  - Familial defective apolipoprotein B (FDB) is due to mutations in the
      apolipoprotein B (apo B) gene at codon 3500 or 3531 that affect low density
      lipoprotein (LDL) receptor binding. From sequence analysis the putative receptor
      binding site was believed originally to be upstream from this at residues 3147
      3157 and 3357-3367. Using denaturing gradient gel electrophoresis, mutations were
      sought in codons 3350-3466. This includes the important positively charged
      residues 3357-3367. DNA from 928 hyperlipidaemic individuals was studied and two
      hitherto unknown DNA changes were discovered, one of which resulted in an altered
      amino acid in the apo B. A known polymorphism Q3405E was also detected at a
      carrier frequency of 1.4%. Using growth of U937 cells as a measure of binding
      affinity of LDL to its receptor the newly discovered mutant A3371V permitted the
      same growth as LDL from normolipidaemic individuals of the U937 cells, however,
      the LDL from Q3405E individuals permitted only 77% of the normal growth
      (P=0.009).

PMID- 9568750
TI  - Serum lipids, lipoprotein(a) and apo(a) isoforms in patients with established
      coronary artery disease and their relation to disease and prognosis after
      coronary by-pass surgery.
AB  - Consecutive patients (n=964) undergoing coronary angiography were studied and
      compared with a random population sample regarding serum lipids and lipoproteins
      with focus on lipoprotein(a) (Lp[a]) levels and apo(a) isoforms. The patients
      were also followed for 5 years after the angiography, and the prognostic value of
      serum lipoproteins were analyzed. The patients were divided in two groups: Group
      1 (n=814) consisted of patients with angina pectoris and at least one coronary
      artery with 50% stenosis and group 2 (n=150) patients with none of the coronary
      arteries significantly obstructed ( < 50%). As controls a random population
      sample was selected (n=197). Blood samples were collected before coronary
      angiography for determination of serum lipids, Lp(a) and isoforms of apo(a). When
      group 1 and group 2 patients were compared, group 1 was found to have higher
      serum cholesterol, triglycerides, apoB and Lp(a) as well as lower HDL and apoAI.
      When group 1 was compared with the random sample, after correction for age and
      sex, similar differences were observed, except that the difference in Lp(a) was
      not significant. The high Lp(a) levels among patients was found to be primarily
      due to the female patients, where the difference compared to both group 2 and
      controls was highly significant (P=0.007 and P=0.001, respectively). There was a
      significant difference in the apo(a) isoform distribution between group 1
      patients and control subjects (P=0.0003), with a higher frequency of low
      molecular weight isoforms among patients. This was also significant for the male
      subgroup (P=0.001). Lp(a), LDL, total cholesterol, triglycerides. apoB, HDL and
      apoAI were significantly related to the number of major coronary arteries with >
      50% stenosis. Mortality during follow-up was,in a univariate analysis,
      significantly correlated to several factors related to the degree of heart
      disease and to LDL (P=0.02) and apoB (P < 0.01). Increased mortality was,
      however, related to low levels of apoB and LDL. For cardiac mortality no
      significant correlation to lipoprotein variables were found. In conclusion
      established lipoprotein risk factors were more frequent among patient with angina
      pectoris and verified coronary stenosis. Furthermore high Lp(a) levels and a high
      frequency of low molecular weight isoforms of apo(a) were found in coronary
      patients. Higher Lp(a) levels were observed both for female and male patients,
      the differences were, however, significant only for the female patients. None of
      the lipoprotein variables could predict coronary death during the follow-up
      period.

PMID- 9568751
TI  - Racial differences in the distribution of a low density lipoprotein receptor
      related protein (LRP) polymorphism and its association with serum lipoprotein,
      lipid and apolipoprotein levels.
AB  - The low density lipoprotein (LDL) receptor-related protein (LRP) is a cell
      receptor that has close structural homology to the LDL and very low density
      lipoprotein receptors and thus is believed to play an important role in lipid
      metabolism. This study was carried out to evaluate the distribution of a known
      tetranucleotide repeat polymorphism in the LRP gene and its association with
      serum lipoprotein-lipid and apolipoprotein levels in four large samples
      comprising Hispanics (n=373) and non-Hispanic Whites (n=522) from the U.S. and
      Nigerian Blacks from Sokoto (n=390) and Benin (n=800). A total of four alleles,
      designated 83, 87, 91 and 95 bp, were observed. The 83 bp allele was observed at
      0.4-1.1% in the two U.S. populations but was completely absent in African Blacks.
      Sokoto Blacks had significantly different frequencies of the 87 and 91 bp alleles
      compared to Hispanics (P=0.008) and non-Hispanic Whites (P=0.024). The frequency
      of the 91 bp allele was also significantly higher in Benin Blacks compared to
      Hispanics (P=0.026) and non-Hispanic Whites (P=0.054). The analysis of the
      relationship between the LRP polymorphism and serum lipid traits yielded some
      significant race and gender specific significant association for lipoprotein(a)
      in non-Hispanic White males (P=0.02); HDL2-cholesterol in Hispanic females
      (P=0.03) and apolipoprotein B in Benin males (P=0.04). We also observed an
      interaction between the LRP polymorphism and menopausal status for Lp(a) in
      Hispanic females (P=0.014). However, considering multiple comparisons were
      performed, these associations could be due to chance. Our data indicate that
      although the LRP tetranucleotide polymorphism exhibits inter-racial differences
      in its distribution, it does not appear to have a significant role in affecting
      serum lipid traits.

PMID- 9568752
TI  - Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on
      arterial endothelial function in patients with severe primary
      hypercholesterolaemia.
AB  - Endothelial dysfunction is an important early event in atherogenesis. Changes in
      arterial endothelial physiology were studied in patients with severe primary
      hypercholesterolaemia participating in an ongoing clinical trial evaluating
      atorvastatin and simvastatin. Endothelial function was assessed non-invasively
      using brachial ultrasound and the primary outcome measure was flow-mediated
      endothelium-dependent dilatation (FMD) in response to reactive hyperaemia.
      Patients were studied upon entry while still using simvastatin 40 mg daily and
      again after a 10-week washout (baseline). Over the next 30 weeks, 20 patients
      received atorvastatin titrated up to 80 mg daily and 12 patients received
      simvastatin titrated up to 40 mg daily (plus cholestyramine 4 g daily in 10/12),
      followed by a final ultrasound study. During simvastatin washout, total and low
      density lipoprotein (LDL) cholesterol rose by a median 23-29% and 30-34%,
      respectively. During atorvastatin therapy, total and LDL cholesterol fell by a
      median of 41 and 46%, respectively, triglycerides fell by 45%, and high density
      lipoprotein (HDL) cholesterol rose by 10%. During simvastatin plus cholestyramine
      therapy, the respective median changes were - 32, - 39, - 44 and + 11%. Patients
      at baseline showed evidence of impaired FMD and this improved significantly on
      either treatment, from a median + 2.2 to + 5.5% on atorvastatin and from + 1.8 to
      + 4.5% on simvastatin plus cholestyramine (P < 0.01 for both treatments). Typical
      response in healthy subjects would be from + 8 to + 9%. FMD at baseline was
      correlated with HDL cholesterol (r=0.49, P < 0.01). Change in FMD was inversely
      correlated with baseline FMD (r=-0.54, P < 0.001). Endothelial dysfunction in
      primary hypercholesterolaemia was improved by treatment with atorvastatin or
      simvastatin plus cholestyramine and this effect may result in the prevention of
      future coronary events.

PMID- 9568754
TI  - Important contribution of lipoprotein particle number to plasma triglyceride
      concentration in type 2 diabetes.
AB  - The aim of the present study was to determine the contributions of particle size
      versus number to differences in plasma triglyceride-rich lipoprotein
      concentrations in patients with type 2 diabetes. Fasting plasma was obtained from
      174 consecutive eligible men and women with type 2 diabetes (with or without
      insulin treatment, mean age 57.0 + 6.3 years) who were undergoing coronary
      angiography. The triglyceride-rich (Sf 12-400) lipoproteins (TRL) were
      subfractionated into the Sf 12-60 and Sf 60-400 subfractions. Particle numbers,
      estimated by measuring apolipoprotein B by electroimmunoassay, in each of these
      lipoprotein fractions were related to enzymatically determined triglyceride
      levels in the triglyceride-rich lipoproteins. Approximately 87% of the
      triglyceride-rich lipoprotein particles were in the Sf 12-60 fraction and 13% in
      the Sf 60-400 fraction. Multiple linear regression indicated that 69% (i.e.
      r2=0.69) of the variance in the triglyceride levels could by explained by
      differences in TRL particle number and 17% (i. e. r2=0.17) by the differences in
      particle triglyceride content. These observations are similar in each gender and
      in those with or without insulin treatment. In conclusion, in type 2 diabetes,
      the vast majority of triglyceride-rich lipoproteins are smaller particles which
      are in the Sf 12-60 fraction. Differences in particle number, rather than
      triglyceride content, account for approximately 70% of the differences in
      triglyceride levels observed between individuals. Previous demonstrations, in
      those without diabetes, of an association between small triglyceride-rich
      lipoproteins with coronary artery disease suggest the importance of these
      findings to the increased atherosclerosis in diabetes.

PMID- 9568753
TI  - Is plaque formation in the common carotid artery representative for plaque
      formation and luminal stenosis in other atherosclerotic peripheral arteries? A
      post mortem study.
AB  - The atherosclerotic carotid artery is easily accessible for non-invasive duplex
      investigation. The aim of the present post mortem study was to examine whether
      plaque accumulation and luminal stenosis in the common carotid artery is
      representative for atherosclerotic plaque accumulation and luminal stenosis in
      other peripheral arteries. A total of 3765 cross-sections were obtained at
      regular intervals from 240 arteries (24 individuals). Five types of peripheral
      arteries were investigated: common carotid, femoral, common iliac, external iliac
      and renal arteries. In each cross-section, the lumen area, vessel area, plaque
      area and maximal plaque thickness was measured. For each location, the percentage
      luminal stenosis and relative plaque area was calculated. Relative plaque area
      was defined as the percentage of the vessel area which was occupied by plaque.
      Weak correlations (r=0.41-0.59) were observed between percentage relative plaque
      area or maximal plaque thickness in the common carotid artery and percentage
      relative plaque area in other peripheral arteries. Neither plaque accumulation
      nor luminal stenosis in the common carotid artery correlated with the percentage
      luminal stenosis in other peripheral arteries (P > 0.05). We conclude that plaque
      area in the common carotid artery is weakly correlated with plaque area and not
      correlated with luminal stenosis in other peripheral arteries.

PMID- 9568755
TI  - Exercise training has little effect on HDL levels and metabolism in men with
      initially low HDL cholesterol.
AB  - Low concentrations of high-density lipoprotein cholesterol (HDL-C) are a
      recognized risk factor for atherosclerotic cardiovascular disease. Exercise is
      often recommended to increase HDL-C, but the effect of exercise training on HDL
      levels and metabolism in subjects with low HDL concentrations is not well
      defined. The present study compared the HDL response to 12 months of supervised
      endurance exercise training without weight loss in 17 men aged 26 49 years with
      initially low ( < 40 mg/dl, N=7) or normal ( > 44 mg/dl, N=10) HDL-C levels. HDL
      C levels and HDL apolipoprotein metabolism were assessed while the subjects
      consumed controlled diets before and after the year of training. Increases in
      total (5.1+/-2.8 versus 1.9+/-4.2 mg/dl, P=0.08) and HDL2 (3.8+/-2.9 versus 0.4+/
      1.1 mg/dl, P=0.01) cholesterol were greater in men with normal initial HDL-C
      levels. Catabolic rates for HDL apolipoproteins decreased 7-14% and biological
      half-lives increased 10-15% after exercise training in subjects with normal HDL,
      but were unchanged in the low HDL-C group. HDL apolipoprotein synthetic rates
      were not consistently affected by exercise training in either group. Postheparin
      lipoprotein lipase activity increased 27%, the clearance rate of intravenous
      triglycerides increased 14%, and apolipoprotein B levels decreased 16% with
      training in subjects with normal HDL-C but were unchanged in the low HDL-C group.
      We conclude that the ability to increase HDL-C levels through endurance exercise
      training is limited in subjects with low initial HDL-C, possibly because exercise
      training in such subjects fails to alter triglyceride metabolism.

PMID- 9568756
TI  - European Lipoprotein Club: report of the 20th annual conference, Tutzing, 8-11
      September 1997.
AB  - The year 1997 celebrated the 20th anniversary of the European Lipoprotein Club.
      Sessions explored topics in the line of classical concepts and forthcoming
      advances in the field of basic and clinical research on lipoproteins.
      Participants from 18 European countries attended the conference. Recent
      Developments in Lipoprotein Research, were reviewed by Thomas Olivecrona (Umea,
      Sweden), who gave a perspective on lipolysis; and Gerd Assmann (Munster,
      Germany), who overviewed epidemiological data of the PROCAM study and focused on
      the biochemical and genetic components of reverse cholesterol transport. Session
      I, chaired by Katriina Aalto Setala (Tampere, Finland) and Marten Hofker (Leiden,
      Netherlands) was dedicated to 'Lipoprotein receptors (old and new)'. Various
      structural and functional aspects were reported for the newcomers in the ever
      enriching LDL receptor gene family (VLDLR, LR7/8B, LR11, Megalin, RAP-related
      proteins). However, a decade of identification of LDL receptors gene defects
      reveals now that phenocopies of familial hypercholesterolemia may be linked to a
      third, yet unknown locus. Identification of pathways which clear HDL is underway.
      Session II, chaired by David Bowyer (Cambridge, United Kingdom) and Richard W
      James (Geneva, Switzerland), was entitled 'Significance of lipoprotein
      heterogeneity (metabolic and pathological aspects)'. Factors involved in
      lipoprotein modification (dense LDL, oxidation), transient production (post
      prandial, VLDL synthesis) or degradation (complement activation) and
      controversial hypotheses on their links with atherosclerosis were discussed.
      Session III on 'Novel methodologies for lipoprotein research' was chaired by
      Rudolph Poledne (Prague, Czech Republic) and Armin Steinmetz (Marburg, Germany).
      Simple technologies for routine assessment of lipoprotein metabolism, as well as
      the most sophisticated ones, to study lipid and free radical exchanges between
      particles, were presented.

PMID- 9568757
TI  - Regional development of glutamate-N-methyl-D-aspartate receptor sites in
      asphyxiated newborn infants.
AB  - The N-methyl-D-aspartate (NMDA) subclass of glutamate receptors was examined in
      newborn infants dying between 25 weeks' gestation and term, either from acute
      cerebral hypoxia, or from other noncerebral conditions incompatible with life.
      Frontal, occipital, temporal, and motor cortex tissue samples were obtained at
      autopsy (post mortem delay: median, 45.9 hr; range, 24-96 hr) and frozen for
      subsequent [3H]MK801 homogenate binding assays. Whereas no significant variation
      was observed in ligand affinity (KD), in all cases receptor density (BMAX)
      increased with gestational age, in occipital cortex (27 weeks, BMAX = 222 +/- 44
      fmol x mg protein(-1); 39 weeks, 439 +/- 42 fmol x mg protein[-1]), but not in
      motor or temporal cortex. The gestational-age increase also occurred in control
      frontal cortex (27 weeks, 284 +/- 80; 39 weeks, 567 +/- 40 fmol x mg protein[
      1]), but was significantly less marked in frontal cortex in hypoxia cases (27
      weeks, 226 +/- 90; 39 weeks, 326 +/- 47 fmol x mg protein[-1]). In all cortical
      areas except temporal, the maximal response to glutamate did not vary across case
      groups. Hypoxia cases showed an increased response to glutamate enhancement
      selectively in temporal cortex. Binding site density did not correlate with
      degree of hypoxia as assessed pathologically, suggesting that receptor
      differences preceded the hypoxic episode. Regional differences in glutamate-NMDA
      receptor sites may underlie increased vulnerability to hypoxia at birth.

PMID- 9568758
TI  - Influence of eye movements on Rett stereotypies: evidence suggesting a stage
      specific regression.
AB  - The influence of eye movements on hand use and pervasive stereotypies in Rett
      syndrome was studied, to better understand the developmental abnormality in this
      disorder. Nine patients in the post-regression phase were offered objects. As
      expected, the girls looked at the objects but usually did not reach for them. Nor
      were their characteristic hand stereotypies altered by such looking. But the
      occurrence of stereotypies was promoted by overall shifts in gaze, ie, eye
      movements in any direction. This finding may be relevant to the late-infancy loss
      of voluntary hand use in Rett syndrome associated with onset of pervasive
      stereotypies. It suggests a stage-specific regression to a level characteristic
      of normal 3-month-old infants who do not reach and grasp, but whose hand clasping
      and mouthing may be triggered by the perceptual consequences of exploratory eye
      movements and shifts in gaze.

PMID- 9568759
TI  - Lamotrigine treatment in childhood drug resistant epilepsy.
AB  - The clinical response to lamotrigine has been evaluated in a group of 63 drug
      resistant epileptic children in an open add-on trial. A negative response was
      observed in 30 subjects. In 11 patients, after an initial improvement lasting a
      mean period of 8 months, seizures recurred with the same frequency present before
      the beginning of the treatment. Twenty-two patients responded to lamotrigine
      treatment. Period of observation in the responsive group ranged from 1 year to 3
      years. Response was complete in 16 patients and in the other 6 a 50% to 90%
      decrease of seizures was obtained. A complete normalization of the
      electroencephalogram (EEG) was registered in 10 cases after a mean period of 5
      months of therapy. Side effects were mild and limited to 12 patients. Improvement
      was obtained in social and academic performance. Writing ability improved in one
      case. Lamotrigine can be considered a useful drug in the therapeutic
      armamentarium for childhood drug resistant epilepsy.

PMID- 9568760
TI  - Children who can't smell the coffee: isolated congenital anosmia.
AB  - Two children with isolated congenital anosmia, a rare syndrome of deficient
      restricted neuronal migration, are presented with early diagnosis confirmed by
      standardized smell testing and detailed neuroimaging studies. Recognition of this
      disorder and its spectrum of presentations provides important insights into the
      molecular mechanisms underlying the development of the olfactory system.

PMID- 9568761
TI  - Early diagnosis of subependymal giant cell astrocytoma in patients with tuberous
      sclerosis.
AB  - We present 19 patients with tuberous sclerosis complex and subependymal giant
      cell astrocytoma. The mean age at the time of tumor diagnosis was 9.4 years
      (range, 1.5 to 21 years). Computed cranial tomography (CT) or cranial magnetic
      resonance imaging (MRI) identified the lesion which was resected in all cases.
      Seven patients had hydrocephalus and there was an interval increase in the tumor
      size or a large tumor without hydrocephalus in 12 patients. Surgical criteria
      included: (1) presence of hydrocephalus; (2) interval increase in tumor size; (3)
      new focal neurologic deficit attributable to the tumor; and/or (4) symptoms of
      increased intracranial pressure. Eight patients were identified through a
      surveillance program involving annual computed cranial tomography. All of these
      eight patients had their tumor removed prior to the development of symptoms, none
      had neurologic deficits which persisted after surgery, and none has so far
      developed recurrent subependymal giant cell astrocytoma. In contrast, of the 11
      patients from the non-surveillance group 7 were symptomatic at tumor diagnosis, 1
      had a complicated postoperative course, 2 developed recurrent giant cell
      astrocytoma, and 1 had an extensive lesion that could not be completely excised.
      Periodic cranial imaging may help to identify subependymal giant cell
      astrocytomas in tuberous sclerosis patients before they become symptomatic.
      Earlier diagnosis and treatment could reduce surgical morbidity and the risk of
      tumor recurrence.

PMID- 9568762
TI  - Abnormal frequency mismatch negativity in mentally retarded children and in
      children with developmental dysphasia.
AB  - The auditory event-related potential waveform termed "mismatch negativity" was
      examined in 12 mentally retarded children with delayed development of speech and
      language (aged 5-8 years) and in 13 children with developmental dysphasia (aged 5
      9 years). The mismatch negativity waves were elicited with pure sine-wave tone
      stimuli using the oddball paradigm. We measured the peak latency and peak
      amplitude of mismatch negativity responses to frequency (500/553 Hz) difference.
      The mismatch negativity patterns were compared with those of 10 children with
      normal development of linguistic skills (aged 5-9 years). In both the mentally
      retarded and dysphasic groups, the peak amplitude of the frequency mismatch
      negativity was significantly attenuated when compared with the control group, but
      no significant difference was observed between the mentally retarded and
      dysphasic groups. Attenuated frequency mismatch negativity was related to
      impairment of linguistic skills irrespective of the child's cognitive skills.
      Because the mismatch negativity response reflects central auditory processing and
      is modal specific for auditory stimuli, this change-specific response can serve
      as an objective tool to elucidate central auditory deficits in children.

PMID- 9568763
TI  - Pain in pediatric Guillain-Barre syndrome: case report.

PMID- 9568764
TI  - Multiple cranial neuropathies: unusual presentation of acute T-cell lymphoma.

PMID- 9568765
TI  - Wernicke's encephalopathy in a child with prolonged vomiting.

PMID- 9568766
TI  - Idiopathic hypoparathyroidism with basal ganglia calcification, epilepsy, and
      interictal focal hyperperfusion.

PMID- 9568767
TI  - Acute cerebellar atrophy in encephalitis.

PMID- 9568768
TI  - Traumatic renal artery occlusion: a review of the literature.
AB  - To better define what constitutes appropriate treatment for traumatic renal
      artery occlusion, we analyzed our experience along with 147 other case reports
      from the literature. We recently reported our 15-year experience with 12 patients
      (13 injuries) who presented to our trauma centers with renal artery occlusion
      secondary to blunt trauma. This experience prompted a review of the literature.
      From this review, we identified an additional 19 cases of bilateral and 128 cases
      of unilateral renal artery occlusion that met our inclusion criteria. Of the 20
      patients with bilateral renal artery occlusion, surgical revascularization was
      attempted in 16 and successful in 9 (56%). Of the 139 patients with unilateral
      renal artery occlusion, surgical revascularization was attempted in 34 and
      successful in 9 (26%). Evidence of decreased renal function was noted in 67% of
      those who had a successful revascularization for unilateral injury at a mean 1.8
      year follow-up, whereas 12% experienced hypertension at a mean 3.1-year follow
      up. Hypertension developed in 34 (32%) of the 105 patients who did not have
      revascularization attempted and was present by a mean 97 days postinjury.
      Surgical revascularization for unilateral renal artery occlusion seldom results
      in a successful outcome. Revascularization is indicated in patients with
      bilateral renal artery occlusion and in those with injury to a solitary kidney.
      Patients who are observed must be followed closely for development of
      hypertension.

PMID- 9568769
TI  - Holmium laser resection of bladder tumors (HoLRBT).
AB  - We investigated the safety, technique, and effectiveness of holmium laser
      resection of bladder tumors (HoLRBT). Data are presented on 23 patients who were
      treated with the HoLRBT technique. Holmium:YAG laser has a wavelength of 2,140
      nm, which is delivered in a pulsed fashion via an end-firing quartz fiber placed
      through a modified resectoscope. Twenty-three patients with newly diagnosed
      transitional cell carcinoma underwent HoLRBT. Cold cup biopsies of the bladder
      tumor base were taken and compared to the HoLRBT specimens. Twenty-two of 23
      patients were discharged catheter-free within 24 hours. One patient required a
      catheter for 3 days. The mean total energy used was 13.14 kJ with a maximum of
      34.31 kJ. Mean resection time was 18.6 minutes. Cold cup biopsy of the tumor base
      did not alter the stage of the bladder tumor. The HoLRBT technique can be used to
      safely and effectively treat bladder tumors. This laser technique did not alter
      the stage or the diagnosis of bladder tumors. Holmium resection of bladder tumors
      usually can be performed as an outpatient catheter-free procedure and is a viable
      alternative to the standard electrocautery transurethral resection of bladder
      tumors.

PMID- 9568770
TI  - Home flow rates in evaluation of lower urinary tract symptoms in men.
AB  - We wanted to determine if 5-second home flow rates can be used in the evaluation
      in men with lower urinary tract symptoms (LUTS). Fifty previously untreated men
      with LUTS were evaluated by history and physical examination, international
      prostate symptom score (IPSS) questionnaire, and two methods of uroflowmetry.
      Each participant underwent three formal uroflow measurements using the Dantec
      UD5500 Mk2 machine and subjective 5-second home uroflow measurements twice daily
      for 7 days. The reliability of each test as well as correlation coefficients
      between the two methods of uroflowmetry were determined. The reliability for the
      average of the 14 home flow rates was 0.99 and the reliability for any single
      home flow was 0.82. Reliability for the average of three uroflows in measuring
      Qmax, Qave, flow times, and volume are 0.91, 0.91, 0.86, and 0.79, respectively.
      If single measurements are used, the values are 0.77, 0.78, 0.68, and 0.56. Home
      flow average is significantly different from Qmax and Qave (p < .001). No
      significant correlation was found between any of the uroflowmetry measurements or
      home flow average and IPSS or bother score. Home flows rates and uroflowmetry are
      reliable tests. There is a weak correlation between average home flows and Qmax
      and Qave. The greatest use of home flow rates probably lies in follow-up of
      patients who had either medical or surgical intervention for LUTS.

PMID- 9568771
TI  - Percutaneous sclerotherapy for varicocele embolization.
AB  - Varicocele is a common cause of male infertility and can be treated surgically or
      by angiographic occlusion of the internal spermatic (testicular) vein. The
      treatment of clinical as well as subclinical varicoceles has been reported to
      improve sperm parameters. Varicocele also can cause scrotal pain and discomfort.
      We treated 89 patients using percutaneous sclerotherapy on an outpatient basis.
      Our technique proved to be simple and effective and was associated with low
      morbidity. At follow-up only three failures occurred.

PMID- 9568772
TI  - Retrograde flexible ureterorenoscopic holmium-YAG laser lithotripsy: the new gold
      standard.
AB  - To demonstrate the efficacy of flexible retrograde ureterorenoscopic holmium-YAG
      intracorporeal laser lithotripsy for the treatment of renal calculi, a total of
      86 patients presenting to our hospital with renal calculi underwent flexible
      retrograde ureterorenoscopic holmium-YAG intracorporeal laser lithotripsy of
      their stones, and the data were collected prospectively. As extracorporeal shock
      wave lithotripsy is not available at our institution, all patients with renal
      calculi in this study were treated in a retrograde fashion using the Richard Wolf
      6.0F semirigid ureteroscope, the 7.5F flexible ureterorenoscope, and the holmium
      YAG laser by Coherent Inc. Except for inhospital consults or patients requiring
      admission secondary to infection, all cases were performed on an ambulatory
      basis. All renal calculi 3 cm or smaller were approached in a retrograde fashion.
      Where possible, the stones were initially debulked using the semirigid
      ureteroscope and the 550-microm fiber followed by the flexible ureterorenoscope
      in combination with the 360- or 200-microm laser fiber depending on stone
      position. Stones were fragmented until they were small enough to be removed by
      hydrocleansing. Using this technique, stone-free success rates for calculi 2.5 cm
      or smaller after a single treatment, regardless of stone composition or location,
      are superior to those of extracorporeal shock wave lithotripsy. For calculi
      between 2.5 and 3 cm, the results also are noted to be superior. We conclude that
      for calculi larger than 3 cm or for partial staghorn calculi, the treatment of
      choice appears to be a percutaneous approach.

PMID- 9568773
TI  - Endoscopic suspension of the prolapsed vaginal dome.
AB  - Complete prolapse of the vaginal dome post hysterectomy is uncommon. However,
      complications such as urinary incontinence, recurrent urinary infections, and
      ureteral obstruction leading to anuria and loss of renal function may result. A
      modified technique for endoscopic suspension of the bladder neck and vaginal
      prolapse, performed in six patients, is presented. The positive results achieved
      after a 64-month of follow-up suggest that this procedure is another safe
      alternative to correct vaginal prolapse and its complications.

PMID- 9568774
TI  - Laparoscopic ureterolithotomy.
AB  - We report about the successful laparoscopic removal of ureteral stones. Since
      July 1993, 21 patients with large ureteral calculi have undergone laparoscopic
      ureterolithotomy. In 19 of 21 patients, laparoscopic ureterolithotomy was
      successful. The mean operating time was 90 minutes. The postoperative inhospital
      stay was 1 to 4 days. Laparoscopic ureterolithotomy offers an alternative to open
      surgery in patients with large ureteral stones or when less invasive measures
      fail.

PMID- 9568775
TI  - Prognostic markers in clinically localized prostate cancer.
AB  - Current dilemmas for physicians managing patients with localized prostate cancer
      include deciding: (1) which patients need aggressive treatment; (2) what
      treatment options are best for a given patient; and (3) what treatment outcomes
      can be expected. This article reviews our ability to prognosticate outcome
      (including pathological stage and disease-free survival rate) in patients with
      clinically localized adenocarcinoma of the prostate (AJCC, stage T1-T2. N0, M0)
      subsequent to analysis of several contemporary series involving patients treated
      with radical prostatectomy and external-beam radiation therapy. Pretherapy
      prostate-specific antigen (PSA) level (< or =4 ng/mL or >20 ng/mL) and Gleason
      score (< or =4 or > or =8) as individual variables provide independent prognostic
      information for only a subset of patients undergoing radical prostatectomy and
      external-beam radiation therapy. Pathological stage is the most powerful
      predictor of outcome following radical prostatectomy, and its prediction (organ
      confined vs. seminal vesicle or lymph node involvement) is aided by knowledge of
      clinical stage, Gleason score, and PSA level. Planned systematic biopsies also
      provide useful prognostic information for the prediction of pathological stage
      and tumor volume, as well as providing additional tissue for pathological
      assessment of tumor heterogeneity. Several novel markers of biological
      aggressiveness are associated with critical steps of the metastatic cascade
      (growth, invasion, angiogenesis, and resistance to apoptosis) and include the p53
      tumor suppressor gene, the bcl-2 proto-oncogene, markers of increased
      proliferation (Ki-67), apoptosis, and angiogenesis (microvessel density). Their
      evaluation in clinical specimens is currently being used to prognosticate
      outcome. Current clinical and pathological parameters provide a "ballpark"
      estimate of outcome for patients with clinically localized prostate cancer.
      Further elucidation of the critical molecular events associated with prostate
      cancer progression and metastasis should help in identifying molecular markers
      that more accurately predict the prognosis for an individual patient with
      clinically localized prostate cancer.

PMID- 9568776
TI  - Percutaneous cystolithotomy after augmentation cystoplasty: comparison with open
      procedures.
AB  - Percutaneous procedures for the removal of calculi from reconstructed bladders
      have not been compared in a single institution with traditional open methods. The
      records of patients undergoing seven percutaneous and six open procedures for the
      removal of calculi from augmented bladders were reviewed. Operative time,
      hospitalization time, complications, stone burden, and recurrence were compared.
      All patients were stone-free at the end of either one or two procedures. Four of
      six patients in the percutaneous group and four of six patients in the open group
      had recurrent bladder calculi during average follow-up of 30 months. The average
      hospital stay was 1.1 days for patients undergoing percutaneous procedures and
      3.7 days for those undergoing open cystolithotomy. Narcotic use was significantly
      lower in the percutaneous group. Percutaneous cystolithotomy is safe, effective,
      and currently the preferred method for removing stones from an augmented bladder.

PMID- 9568777
TI  - Endoscopic ureteroneocystostomy: palliative urinary diversion in advanced
      prostatic cancer.
AB  - Distal ureteral obstruction is a common complication in advanced prostatic
      cancer, secondary to direct compression at the ureterovesical junction and/or
      invasion of the ureteral orifice and/or of the intramural ureter by the tumor.
      The ureteral orifice may not be readily visible to the trigone-infiltrating
      tumor, but remains superficial as it is pushed upward by the tumoral tissue. The
      indications for palliative diversion in patients with pelvic malignant disease
      and renal failure from ureteral obstruction remain controversial. We present the
      results of our endoscopic ureteroneocystostomy technique by which the trigone is
      resected to restore continuity of the ureteral orifice and to place a double
      pigtail ureteral stent. Of the 31 operations performed for obstructive prostate
      cancer, continuity was restored in 76% of cases. Length of hospital stay was
      gradually reduced to a few days. Median survival after surgery was 8 months (0.25
      to 27.5 months). Palliative diversion may be considered a reasonable option for
      many patients, even in the case of an apparently unpassable obstruction of the
      pelvic ureter, thereby prolonging survival and improving quality of life.

PMID- 9568778
TI  - Guidewire fragmentation during holmium:YAG laser endopyelotomy.
AB  - A guidewire fracture is a rare complication of laser surgery. We report that this
      rare complication occurred during a retrograde endoureteropyelotomy with the
      holmium:YAG laser. No data are available about the safety of commonly used
      guidewires. A comparative in vitro study was performed with two types of
      guidewires to assess their resistance. At all energy levels tested, a Teflon
      coated guidewire performed best in the present safety test.

PMID- 9568779
TI  - Intracorporeal needle breakage as an unusual complication of intracavernous self
      injection.
AB  - Intracorporeal needle breakage during intracavernous self-injection of vasoactive
      drugs in the treatment of erection disorders represents an unusual complication.
      This article presents a case of intracorporeal needle breakage during self
      injection in a 50-year-old man. Our case allowed an immediate removal of the
      needle by manipulation, without resorting to surgery or delayed retrieval.

PMID- 9568780
TI  - Long-term survivors of cancer.

PMID- 9568781
TI  - Long-term cancer patient survival in the United States.
AB  - Although survival rates are useful for monitoring progress in the early detection
      and treatment of cancer and are of particular interest to patients with new
      diagnoses, there are limited population-based estimates of long-term survival
      rates. We used data collected by the Surveillance, Epidemiology, and End Results
      Program for cases diagnosed during 1974-1991 and followed through 1992 to
      estimate relative survival at 5, 10, and 15 years after diagnosis of cancer of
      the breast, prostate, colon and rectum, and lung. Relative survival after
      diagnosis of breast and prostate cancer continued to decline up through 15 years
      after diagnosis, whereas survival after diagnosis of lung and colon or rectal
      cancer remained approximately constant after 5 and 10 years, respectively. Age
      specific patterns of survival varied by site, stage, and demographics. Among
      patients with localized breast and prostate cancer, women who were younger than
      age 45 at breast cancer diagnosis and men who were 75 years and older at prostate
      cancer diagnosis had the poorest relative survival. Relative survival among lung
      cancer patients decreased with age at diagnosis, regardless of stage or
      demographics, and age-specific patterns of relative survival for patients with
      cancer of the colon and rectum differed according to race. Among white patients
      diagnosed with cancers of the colon and rectum, relative survival did not vary by
      age at diagnosis; among black patients older than 45 at diagnosis, relative
      survival decreased with age. This study provides population-based estimates of
      long-term survival and confirms black/white, male/female, and stage- and age
      specific differences for the major cancers.

PMID- 9568782
TI  - Associations of plasma carotenoid concentrations and dietary intake of specific
      carotenoids in samples of two prospective cohort studies using a new carotenoid
      database.
AB  - Diet-plasma carotenoid associations were examined in samples of women and men
      from each cohort in the Nurses' Health Study and the Health Professionals Follow
      Up Study. In each sample, participants completed two self-administered food
      frequency questionnaires with at least a 1-year interval and provided a blood
      specimen preceding the second food frequency questionnaire. Carotenoid intakes
      were estimated from values for the five major carotenoids found in human plasma,
      specifically, alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene,
      using the United States Department of Agriculture-National Cancer Institute
      Carotenoid Database, as well as updated values for tomato products. Pearson
      correlation coefficients were calculated to compare diet-plasma correlations over
      time by sex after adjustment for recognized covariates. Among nonsmoking women (n
      = 162), the adjusted diet-plasma carotenoid associations were 0.48 for alpha
      carotene, 0.27 for beta-carotene and lutein, 0.32 for beta-cryptoxanthin, and
      0.21 for lycopene. Among nonsmoking men (n = 110), diet-plasma correlations were
      0.47 for alpha-carotene and lycopene, 0.35 for beta-carotene, 0.43 for beta
      cryptoxanthin, and 0.40 for lutein. Correlations between total fruit or vegetable
      intake and each plasma carotenoid level were not as high as any of the calculated
      carotenoid intake using the new database values. The correlations observed in
      this study indicate that the new carotenoid database provides valuable
      information on specific carotenoid intake and may be useful in epidemiological
      studies that attempt to account for associations between fruit or vegetable
      intake and disease.

PMID- 9568783
TI  - Dietary and supplemental calcium and the recurrence of colorectal adenomas.
AB  - The association between calcium intake and the risk of colorectal neoplasia
      remains controversial. This analysis prospectively investigated the association
      between dietary and supplemental calcium intake and recurrent colorectal
      adenomas. Participants were part of a multicenter, randomized clinical trial of
      antioxidant vitamins. The study endpoints were adenomas detected between
      surveillance colonoscopies conducted at approximately 1 year and 4 years after
      study entry. Baseline intake of energy-adjusted calcium derived from a food
      frequency questionnaire was used as the main exposure of interest. Calcium
      supplement use was assessed by semiannual questionnaires. Logistic regression was
      used to compute odds ratios and 95% confidence limits, and Poisson regression was
      used to estimate rate ratios. Subjects in the fifth quintile of dietary calcium
      had an adjusted odds ratio of 0.72 (95% confidence interval, 0.43-1.22) compared
      to those in the lowest quintile. Investigation of the numbers of adenomas yielded
      stronger findings: the rate ratio for the fifth quintile versus the first was
      0.63 (95% confidence interval, 0.39-1.02). Dietary calcium seemed to have a
      greater effect among individuals with a high-fat diet than among those with a low
      fat diet; however, the interaction was not statistically significant. Use of
      calcium supplements was not related to adenoma recurrence. These results suggest
      that a high calcium intake may be associated with a reduction in risk of
      recurrent adenomas, especially among individuals on a high-fat diet.

PMID- 9568784
TI  - Mutations of p53 in gallbladder carcinomas in high-incidence areas of Japan and
      Chile.
AB  - Gallbladder adenocarcinomas from patients in two high-prevalence areas, Niigata
      (Japan) and Santiago (Chile), were analyzed for acquired mutations in exons 5-8
      of the p53 tumor suppressor gene, and the characteristics of p53 alterations in
      the two groups were compared. Of 42 tumors, 22 (52.4%) harbored 25 alterations
      identified by PCR amplification and direct sequencing (13 of 22 tumors from
      Niigata and 12 of 20 tumors from Santiago). All alterations were single base pair
      substitutions, 20 (80%) leading to an amino acid substitution or a chain
      termination signal, and 5 (20%) were silent. Immunohistochemically, 55 of 84
      cases (65.5%) showed overexpression of p53 protein, with no significant
      difference in frequency between the two areas. Missense mutations correlated
      highly with overexpression of the p53 protein (93.4%). Mutations of p53 occurred
      in all four exons examined, most commonly in exon 5, but in no particular "hot
      spot." In base-change spectra, all 12 mutations from Santiago showed transitions,
      with 4 arising at the CpG dinucleotide (33.3%). In contrast, no such transition
      was found at CpG sites in Niigata, and 4 of 13 mutations (30.8%) were
      transversions. The data indicated that p53 mutations are highly important in
      carcinogenesis in the gallbladder. In addition, the difference in p53 mutational
      spectra in Niigata and Santiago indicate a likely regional difference in
      mutagenesis.

PMID- 9568785
TI  - p53 mutations in malignant gliomas.
AB  - A population-based series of incident cases of malignant glioma were analyzed for
      mutations in the tumor suppressor gene p53. Exons 4-8 were screened using PCR
      single-strand conformation analysis and confirmed through direct sequencing. Of
      62 tumors analyzed, 12 (19%) contained mutations in p53: one 18-bp duplication in
      exon 5, five point mutations in exon 4, three point mutations in exon 7, two
      point mutations in exon 8, and a splice-site mutation at the exon 6/intron 7
      boundary. In contrast to previous studies of malignant glioma, the prevalence of
      transversion mutations (56%) was higher than transition mutations (33%). A large
      proportion of transversion mutations occurred in exon 4, a region that is not
      routinely screened in gliomas. We present here an improved method for screening
      exon 4 (and other GC-rich regions) of p53 using PCR-single-strand conformation
      analysis. The high frequency of transversion mutations suggests a role for
      exogenous carcinogens in the etiology of malignant glioma.

PMID- 9568787
TI  - Prostate-specific antigen production in the female breast: association with
      progesterone.
AB  - Prostate-specific antigen (PSA) is produced by the female breast. Prior in vitro
      evidence suggests that PSA expression in breast epithelial cells is regulated by
      androgens and progestins but not estrogens. The purpose of this study was to
      determine whether (a) PSA expression in breast nipple aspirate fluid (NAF) and in
      serum is influenced by progesterone (PG); (b) the ability to obtain NAF decreases
      with repeated breast aspirations; and (c) PSA in NAF correlates with abnormal NAF
      cytology. Eight pre- and three postmenopausal women with no breast cancer risk
      factors were enrolled in a pilot study and had NAF and serum collected every 3-4
      days for a month to evaluate the influence of serum PG, luteinizing hormone,
      estradiol, and follicle-stimulating hormone on PSA in serum and in NAF. NAF was
      obtained in 99% (112 of 113) of aspiration visits. Median, mean, and peak NAF but
      not serum PSA levels were higher in pre- than in postmenopausal subjects. NAF PSA
      levels were associated with the rise or peak in serum PG in seven of eight
      premenopausal women (seven of seven with a PG surge) and in zero of three
      postmenopausal women. Considering all 11 women, there was an association between
      NAF PSA and PG (P = 0.005) but not luteinizing hormone, estradiol, or follicle
      stimulating hormone. NAF volume did not significantly change over time. Atypical
      hyperplasia (9%) and hyperplasia without atypia (36%) were identified in the NAF
      of a subset of the subjects. Median, mean, and peak levels of NAF PSA (P = 0.05,
      0.05, and 0.10, respectively) were higher in subjects with normal versus
      hyperplastic cytology. PSA production in the breast increases in association with
      PG. With aspiration every 3-4 days, NAF volume does not significantly decrease
      over time. NAF cytology and PSA levels in NAF may help identify women at
      increased breast cancer risk. Changes in biomarkers of breast cancer risk in NAF
      (including PSA and cytology) may predate mammographic abnormalities. NAF may,
      therefore, be useful as a breast cancer screening tool for young women who are
      not recommended to undergo mammography and as an adjunct to screen women who have
      mammograms performed.

PMID- 9568786
TI  - Reduced expression of hMLH1 and hGTBP/hMSH6: a risk factor for head and neck
      cancer.
AB  - Head and neck cancer, like lung cancer, is considered a paradigm of an
      environmentally induced disease. Genetically determined variation in DNA repair
      capacity is thought to contribute to susceptibility to tobacco-related cancers.
      In this molecular epidemiology study, we investigated the association between DNA
      mismatch-repair (MMR) gene expression and the risk of head and neck cancer. Using
      our newly developed multiplex reverse transcription-PCR assay, we simultaneously
      evaluated the relative expression levels of five MMR genes (hMSH2, hMLH1, hPMS1,
      hPMS2, and hGTBP/hMSH6) in the peripheral blood lymphocytes of 78 patients (mean
      age = 59.6 +/- 12.4 years) with newly diagnosed head and neck cancer and 86
      healthy controls (mean age = 58.2 +/- 12.9 years). The relative MMR gene
      expression was not correlated with disease stage or tumor site in the cases or
      with smoking and alcohol use in the controls. The expression levels increased
      with age in both cases and controls, but the mean expression of hMLH1, hPMS1, and
      hGTBP/hMSH6 was significantly lower in the cases than in the controls (P < 0.05).
      Using the median expression level in controls as the cutoff value, significantly
      increased odds ratios (ORs) were associated only with low expression of hMLH1 (OR
      = 4.4; 95% confidence interval = 2.1-9.1) and hGTBP/hMSH6 (OR = 2.1; 95%
      confidence interval = 1.1-4.1) after adjustment for age, sex, ethnicity, smoking
      status, and alcohol use. The results suggest that low hMLH1 and hGTBP/hMSH6
      expression is associated with an increased risk of head and neck cancer.
      Additional studies with a larger number of subjects are warranted to confirm
      these findings.

PMID- 9568788
TI  - DNA repair and mutagen sensitivity in patients with triple primary cancers.
AB  - The purpose of this study was to measure DNA repair capacity and mutagen
      sensitivity in patients who have had three or more primary forms of cancer. It
      was hypothesized that, if abnormalities in DNA repair and mutagen sensitivity
      were cancer susceptibility factors, such findings would be seen with regularity
      in individuals with multiple primary cancers. DNA repair capacity was measured by
      determining repair of UV-irradiated plasmid DNA (pCMVCAT) transfected into
      peripheral blood lymphocytes. Results from 18 patients and a like number of age-
      and sex-matched controls demonstrated a significant difference in DNA repair
      capacity (P < 0.0001; odds ratio = 14). Mutagen sensitivity was measured by
      determining the mean number of chromatid breaks per cell after in vitro exposure
      to either bleomycin or 4-nitroquinoline-1-oxide. The difference in mean bleomycin
      or 4-nitroquinoline-1-oxide-induced mutagen sensitivity between cases and
      controls was not statistically significant. Fourteen of the 18 patients had
      positive family histories of cancer; in 10, the history was compatible with
      cancer susceptibility syndromes. Although the numbers were small, there was no
      suggestion in this study that treatment or the presence of cancer was the cause
      of the DNA repair abnormalities encountered. These findings support the concept
      of diminished DNA repair capacity as an underlying feature in the development of
      a mutator phenotype.

PMID- 9568789
TI  - Hormone replacement therapy and risk of colon and rectal cancer.
AB  - The hypothesis that sex hormones may influence colorectal cancer risk was
      formulated in the early 1980s, but epidemiological studies on a relationship
      between colorectal cancer risk and hormone replacement therapy (HRT) have only
      accumulated over the last few years. To investigate the relationship between HRT
      and colon and rectal cancer and the role of other covariates that might modify
      it, we analyzed combined data from two case-control studies conducted in Italy
      between 1985 and 1996, including 994 women with incident colon cancer, 542 with
      rectal cancer, and 3110 controls with acute, non-neoplastic, nondigestive, non
      hormone-related disorders. Odds ratios (ORs) and 95% confidence intervals (CIs)
      were derived from unconditional multiple logistic regression equations including
      terms for age, center/study period, education, family history of colorectal
      cancer, status and age at menopause, parity, use of oral contraceptives, total
      energy intake, and body mass index. Ever use of HRT was inversely associated with
      cancer of the colon (OR = 0.64, 95% CI = 0.46-0.88) and of the rectum (OR = 0.46,
      95% CI = 0.29-0.72). Increasing duration of use of HRT was related to decreasing
      risk for colon and rectal cancers (P for trend < 0.01). No interaction emerged,
      and the inverse association persisted across separate strata of other risk
      factors. This study, one of the largest case-control investigations on exogenous
      female hormones and colorectal cancer thus far, provides further evidence that
      women who have ever used HRT are at lower risk of colon and rectal cancer.
      Because colorectal cancer is the second most common neoplasm and cause of death
      among nonsmoking women in developed countries, these results may have a major
      public health impact.

PMID- 9568790
TI  - The association between baseline vitamin E, selenium, and prostate cancer in the
      alpha-tocopherol, beta-carotene cancer prevention study.
AB  - The association between prostate cancer and baseline vitamin E and selenium was
      evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer
      Prevention Study (n = 29,133). During up to 9 years of follow-up, 317 men
      developed incident prostate cancer. Multivariate Cox proportional hazards models
      that adjusted for intervention group, benign prostatic hyperplasia, age, smoking,
      and urban residence were used to evaluate associations between prostate cancer
      and exposures of interest. There were no significant associations between
      baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate
      cancer overall. The associations between prostate cancer and vitamin E and some
      of the baseline dietary tocopherols differed significantly by alpha-tocopherol
      intervention status, with the suggestion of a protective effect for total vitamin
      E among those who received the alpha-tocopherol intervention (relative risk was
      1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07).

PMID- 9568792
TI  - Concentrations of carotenoids, tocopherols, and retinol in paired plasma and
      cervical tissue of patients with cervical cancer, precancer, and noncancerous
      diseases.
AB  - Paired blood (collected after an overnight fast) and cervical tissue (cancerous,
      precancerous, and noncancerous) samples were obtained from 87 patients (age, 21
      86 years) who had a hysterectomy or biopsy due to cervical cancer, precancer
      (cervical intraepithelial neoplasia I, II, and III), or noncancerous diseases.
      The samples were analyzed using high-performance liquid chromatography for 10
      micronutrients (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene,
      beta-carotene, cis-beta-carotene, alpha-tocopherol, gamma-tocopherol, and
      retinol). The results indicated that: (a) among the three patient groups, the
      mean plasma concentrations of all micronutrients except gamma-tocopherol were
      lowest in the cancer patients; however, the mean tissue concentrations of the two
      tocopherols and certain carotenoids were highest in the cancerous tissue; and (b)
      among the 10 micronutrients, only the concentrations of beta-carotene and cis
      beta-carotene were lower in both the plasma and tissue of cancer and precancer
      patients than in those of noncancer controls. These results suggest that: (a) not
      all of the micronutrient concentrations in plasma reflect the micronutrient
      concentrations in cervical tissue; thus, in some cases, it may be necessary to
      measure the tissue micronutrient concentrations to define the role of the
      micronutrients in cervical carcinogenesis; and (b) maintaining an adequate plasma
      and tissue concentration of beta-carotene may be necessary for the prevention of
      cervical cancer and precancer.

PMID- 9568791
TI  - White blood cell DNA adducts, smoking, and NAT2 and GSTM1 genotypes in bladder
      cancer: a case-control study.
AB  - We conducted a case-control study on 114 bladder cancer patients and 46 hospital
      controls. DNA adducts were measured in WBCs by 32P postlabeling and showed no
      association with smoking habits and the glutathione-S-transferase M1 genotype. A
      strong association between adduct levels and the N-acetyltransferase (NAT2)
      genotype was found (P = 0.0002). The NAT2 genotype was associated in a
      nonstatistically significant way to the case-control status (odds ratio, 1.6; 95%
      confidence interval, 0.8-3.2). In a logistic regression model, the log of DNA
      adduct levels was associated in a highly significant way to the risk of bladder
      cancer (regression coefficient, 0.75; P = 0.0006), independently of smoking
      habits. Using the median of DNA adducts (RAL, 0.3) as a cutoff point, the odds
      ratio for the risk of bladder cancer was 4.1 (age-adjusted; 95% confidence
      interval, 1.9-9.0). Our study suggests that sources other than tobacco smoke
      contribute to the formation of aromatic DNA adducts in WBCs. The role of WBC-DNA
      adducts in predicting bladder cancer is still to be clarified.

PMID- 9568793
TI  - Blood and urine levels of tea catechins after ingestion of different amounts of
      green tea by human volunteers.
AB  - The inhibitory activity of tea against tumorigenesis has been demonstrated in
      many animal models and has been suggested by some epidemiological studies. Such
      activity has generally been attributed to tea catechins. To understand the
      bioavailability of tea catechins in humans, we gave 18 individuals different
      amounts of green tea and measured the time-dependent plasma concentrations and
      urinary excretion of tea catechins. After taking 1.5, 3.0, and 4.5 g of
      decaffeinated green tea solids (dissolved in 500 ml of water), the maximum plasma
      concentration (Cmax) of (-)-epigallocatechin-3-gallate (EGCG) was 326 ng/ml, the
      Cmax of (-)-epigallocatechin (EGC) was 550 ng/ml, and the Cmax of (-)-epicatechin
      (EC) was 190 ng/ml. These Cmax values were observed at 1.4-2.4 h after ingestion
      of the tea preparation. When the dosage was increased from 1.5 to 3.0 g, the Cmax
      values increased 2.7-3.4-fold, but increasing the dose to 4.5 g did not increase
      the Cmax values significantly, which suggested a saturation phenomenon. The half
      life of EGCG (5.0-5.5 h) seemed to be higher than the half-life of EGC or EC (2.5
      3.4 h). EGC and EC, but not EGCG, were excreted in the urine. Over 90% of the
      total urinary EGC and EC was excreted within 8 h. When the tea dosage was
      increased, the amount of EGC and EC excretion seemed to increase, but a clear
      dose-response relationship was not observed. The present study provides basic
      pharmacokinetic parameters of green tea catechins in humans; these parameters may
      be used to estimate the levels of these compounds after drinking tea.

PMID- 9568794
TI  - Correspondence re: L. Kohlmeier et al., Adipose tissue trans fatty acids and
      breast cancer in the European Community multicenter study on antioxidants,
      myocardial infarction, and breast cancer. Cancer Epidemiol. Biomark. Prev., 6:
      705-710, 1997.

PMID- 9568795
TI  - Distinct patterns of T cell receptor distribution of peripheral blood CD8+ cells
      during different stages of chronic infection with hepatitis B virus.
AB  - We compared the Vbeta TCR repertoires of CD8+ peripheral blood lymphocytes
      between 21 patients with chronic hepatitis B (CHB) and 9 healthy individuals,
      using RT-PCR analysis. Several differences were seen between CHB patients and
      controls, including a marked increase in the expression of two to five Vbeta
      families in the CHB patients. There was no evidence for a superantigen effect,
      although an increase in Vbeta7 was seen in 64% of patients. A significant under
      expression of Vbeta families were also detected, particularly in patients with
      active liver disease in which under-expression of Vbeta14 and Vbeta15 was
      associated with acute exacerbations of liver disease. We also did a longitudinal
      analysis of the TCR repertoire in two patients over a period of 6 months, from
      the initiation of a disease flare to its resolution. One patient continued to
      experience spontaneous flares following the completion of this study, while the
      other patient underwent spontaneous remission with long-term (> 12 months) loss
      of HBeAg following resolution of the flare. The TCR repertoires of both patients
      were altered during the flare, and there was a higher degree of TCR variability
      in the patient who went into remission.

PMID- 9568796
TI  - The influence of major histocompatibility complex class II genes and T-cell Vbeta
      repertoire on response to immunization with HBsAg.
AB  - Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients
      and is possibly caused by a defect in the T helper cell compartment. The immune
      response to HBsAg is influenced by genes of the major histocompatibility complex.
      We have investigated MHC class I and class II antigens in 53 adult responders and
      73 nonresponders. Results obtained in this first study were tested in a second
      study with 56 responders and 62 nonresponders from an infant vaccination trial.
      In addition, the peripheral Vbeta-chain T-cell receptor repertoire was
      investigated using monoclonal antibodies and flow-cytometry in 26 adult
      responders and 38 nonresponders. As previously reported, nonresponsiveness to
      HBsAg vaccination was associated with DRB1*3 and DRB1*7. In addition, DRB1*13 was
      significantly increased among vaccine responders (35.2% vs 5.4%;p < 0.0001)
      suggesting an immune response promoting effect for this allele whereas the
      closely related allele DRB1*14 was associated with nonresponse in the infant
      study. There was no evidence for a hole in the T cell receptor Vbeta repertoire.
      In conclusion, in agreement with results obtained in mice there appears to be a
      hierarchy of DRB1* genes in the HBsAg immune response. The possible differential
      association of DRB1*13 and DRB1*14 may allow the identification of differences
      between responsiveness and nonresponsiveness to a few amino acid differences in
      the beta1-domain of the class II heterodimer.

PMID- 9568797
TI  - Cytokine profile associated to effector functions of human T cell clones specific
      for Schistosoma mansoni antigens.
AB  - T cell lines and clones specific for Schistosoma mansoni antigens were
      established to study cellular immunity in human schistosomiasis. Flow cytometric
      analysis of the clones demonstrated that all of them were of the helper inducer T
      cell subset (CD3+, CD4+, CD8-), and expressed the alphabeta T cell receptor,
      besides the IL-2 low affinity receptor CD25. Lymphokine analysis revealed that
      clones presented Th1, Th2, or either Th0 patterns of secretion. More
      interestingly, the capability of clones to induce in vitro granuloma reactions
      seems to be related to the presence of TNF-alpha and the absence of IL-10. In
      counterpart, IL-10 producer clones did not help in vitro granuloma formation,
      even in the presence of TNF-alpha.

PMID- 9568798
TI  - Long-term T cell immune reconstitution in 2 SCID patients after BMT.
AB  - To evaluate the long-term reconstitution of the T cell immune repertoire in
      recipients of an allogeneic Bone Marrow Transplantation (allo-BMT), we have
      analyzed the T cell receptor (TCR) repertoire in the periphery and the T cell
      response against tetanus toxoid in two T- B+ Severe Combined Immunodeficiency
      Disease (SCID) patients more than 11 years after HLA haplo-identical allo-BMT.
      Our studies demonstrate that in the periphery of allo-BMT recipients, on the
      basis of TCR V-gene segment usage, the T cell immune repertoire long after allo
      BMT is diverse, as is that of the donor. However, when donor and allo-BMT
      recipient were compared, differences were noted in the TCR Complementarity
      Determining Region 3 (CDR3) size distributions and in the T cell response against
      tetanus toxoid. In particular, the tetanus toxoid specific T cell clones differed
      in their use of HLA restriction elements, and expressed different T cell
      receptors. Moreover, we have uncovered donor-type tetanus toxoid specific T cell
      clones which were established from allo-BMT recipient derived peripheral blood
      lymphocytes and were found to be restricted by the non-shared recipient allele.
      This observation suggests a role for recipient-mediated T cell selection
      processes, in the thymus or at extra-thymic sites.

PMID- 9568799
TI  - Interferon-alpha therapy in HCV hepatitis: HLA phenotype and cirrhosis are
      independent predictors of clinical outcome.
AB  - Interferon-alpha therapy is effective in only approximately 20% of individuals
      with chronic HCV infection. A knowledge of the genetic and/or environmental
      factors that underlie this heterogeneity of response should provide useful
      predictors of clinical outcome. HCV infected patients and healthy subjects were
      selected from the expatriate Egyptian population living in Qatar, where chronic
      HCV infection poses a serious health problem. HCV infection was confirmed by
      ELISA and RT-PCR. Fifty five patients received interferon-alpha therapy for 6
      months and their response was assessed by liver enzyme activity and histology of
      liver biopsies; the patient responses were followed during treatment and for 1
      year afterwards. Twenty five patients were characterised as responders, and the
      remaining 30 as non-responders. All individuals in the study were typed for HLA
      class II alleles. Data were analysed by univariate and multivariate statistical
      methods. Expression of the HLA DR2 Major Histocompatibility class II allele is
      significantly associated with a beneficial response to interferon-alpha therapy
      in Egyptian patients (p < 0.005). This association is independent of cirrhosis,
      the absence of which also showed a significant association with response to
      therapy (p < 0.005). Our results therefore provide evidence that HLA DR2 is an
      important additional factor for predicting a long term response to interferon
      alpha therapy in chronic HCV hepatitis.

PMID- 9568800
TI  - HLA-A*24-B*07-DRB1*01 haplotype implicated with genetic disposition of peak bone
      mass in healthy young Japanese women.
AB  - HLA exhibits the most extensive polymorphism of any of the known human genes and
      is known as a genetic marker which allows genetic background of many diseases and
      physical phenomena. In this study, we, therefore, tried to investigate the
      regulation of HLA polymorphism and peak bone mass (PBM) in order to elucidate the
      genetic backgrounds of bone metabolism in young women. Subjects were 67 healthy
      young Japanese women (average age: 23.6 +/- 2.6 years, Body Mass Index (BMI):
      19.9 +/- 2.0 who were randomly chosen. Allelic polymorphisms in HLA class I (HLA
      A and -B) and HLA-class II (DRB1) were investigated by PCR-SSOP and PCR-SSP.
      Vitamin D Receptor (VDR) and Estrogen Receptor (ER) gene polymorphisms were also
      analyzed. Lifestyle factors, such as exercise and nutrition, were examined by
      questionnaire. Bone mineral density was examined using with Lunar DPX-L. Subjects
      who possessed HLA-B*07 had a significantly lower PBM than those without B*07 (p <
      0.05). All subjects were divided into 3 groups according to HLA haplotypes linked
      with HLA-B*07, as follows: A*24(+/-)B*07(-)DRB1*01(+/-), A*24(+)B*07(+)DRB1*01(
      ), and A*24(+)B*07(+)DRB*01(+). There were no significant differences between
      these three groups in factors that affect bone metabolism, such as age, age at
      menarche, BMI, calcium intake, exercise habits, VDR or ER allele frequency. The
      HLA-A*24-B*07-DRB1*01 haplotype had a significantly lower Z score in the lumbar
      spine compared with subjects without this haplotype (p < 0.05). When the Z score
      was divided by values higher or lower than +1 or -1, all 3 subjects whose Z score
      was lower than -1.0 were found to have the HLA-A*24-B*07-DRB1*01 haptotype. A
      significant association between HLA-A*24-B*07-DRB1*01 and Z score < -1 was found
      (Yate's correction chi(2) = 10.82, p = 0.001, RR = 204). In conclusion, the HLA
      A*24-B*07-DRB*01 haplotype can be considered a new genetic marker implicated with
      low PBM in healthy young Japanese women.

PMID- 9568801
TI  - HLA-B*5101 in Greek patients with Behcet's disease.
AB  - Behcet's disease (BD) is a recurrent systemic vasculitis of unknown etiology.
      Genetic factors and infectious agents seem to be related to the etiology and
      pathogenesis of the disease. BD is strongly associated with HLA-B51 antigen in
      many ethnic groups. As there are differences in HLA profile in different ethnic
      groups, we designed this case-control study to examine the association of HLA-B51
      alleles and BD as well as to investigate the influence of sex, age at development
      of the International Study Group (ISG) for Behcet's Disease criteria and certain
      features of disease severity on the strength of this association. The study
      includes 62 Greek BD patients who fulfill the ISG criteria for Behcet's disease
      and 87 controls. Serological HLA Class-I typing was performed by standard
      microlymphocytotoxicity technique. HLA-DNA typing for the B5 group was performed
      in all B51 subjects and controls by PCR-SSO. Allele B*5101 was found in 80% of BD
      patients and in 26% of controls (odds ratio (OR) 10.48, p < 10[-6]). Males who
      carry this allele have a higher risk than females for BD (OR 16.97 and 5.74
      respectively). B*5101 predisposes to BD at a younger age in both sexes and to the
      development of erythema nodosum (OR = 11, p = 0.004). This was confirmed by
      multiple logistic regression analysis. A weak but not significant association was
      found between B*5101 and uveitis (OR = 2). No association was found between
      B*5101 and vasculitis or skin lesions in either sex. It was concluded that in the
      Greek population allele B*5101 is a predisposing marker for BD, as in most ethnic
      groups, and that this allele predisposes to the development of the disease at a
      younger age in both sexes and to the development of erythema nodosum.

PMID- 9568802
TI  - Nomenclature for factors of the HLA system, update January 1998. WHO Nomenclature
      Committee for factors of the HLA system.

PMID- 9568803
TI  - Effect of cell density on hormonal secretion from human pituitary adenomas in
      vitro.
AB  - Cell density effects were investigated on tumorous hormonal secretion from 10
      pituitary adenomas: 3 somatotrophinomas secreting GH and PRL; 7
      gonadotrophinomas, 3 co-secreted both FSH and LH, all 7 secreted LH.
      Enzymatically dispersed tissue was plated out in 24-well plates at 5 x 10(5),
      10(5), 5 x 10(4) and 10(4) cells/well in serum-free media. Media were collected
      weekly for 2 weeks. RESULTS: In 3 of 3 somatotrophinomas, GH and PRL secretion
      was higher (p < 0.05) at both week 1 and 2 from 10(4) cells/well, but similar at
      other cell densities. In all 3 gonadotrophinomas, the FSH secretory rate was
      highest at 5 x 10(5) cells/well which fell as cell density decreased. Conversely,
      in 7 of 7 gonadotrophinomas the LH secretory rate was highest at 10(4) cells/well
      (p < 0.01) which fell as cell density increased. CONCLUSION: These data suggest
      that paracrine factors may modulate tumorous GH, PRL, FSH and LH secretion, and
      show that FSH and LH secretion vary inversely as cell density increases.

PMID- 9568804
TI  - Effects of long-term growth hormone therapy on adrenal steroidogenesis in Turner
      syndrome.
AB  - It has been shown that growth hormone (GH) and insulin-like growth factor-1
      (IGF1) enhance steroidogenesis responsiveness to ACTH in cultured adrenal cells.
      To investigate the GH effect on adrenal steroidogenesis in non-GH-deficient
      subjects, we studied 9 girls with Turner syndrome (chronological age 5.5-7.2
      years; bone age 5-7 years). In all subjects an ACTH test (Synacthen depot, 0.25
      mg i.v. with blood samples at 0 and 60 min) was performed basally at 8-9 a.m. and
      6 months after GH therapy (1 IU/kg/week). 17-Hydroxypregnenolone (17PGN), 17
      hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHA), its sulfate (DHA-S),
      androstenedione and cortisol were evaluated by radioimmunoassay. Two groups of
      normal girls were selected as controls: group A age-matched the patients at the
      start of the study, and group B age-matched the patients at the end of the study.
      The responsiveness of each hormone to ACTH was expressed as the difference
      between stimulated and basal values. A p value of < 0.01 was considered to
      indicate significance. There were no significant differences between pre- and
      posttreatment basal values of 17PGN, 17OHP, DHA, androstenedione and cortisol in
      the Turner syndrome patients, whereas a significant increase was observed for
      basal DHA-S (1.57+/-0.31; 1.89+/-0.43 micromol/l, p < 0.01). Comparison of
      increments before and after GH treatment showed a significant increase in
      responsiveness to ACTH after GH therapy DHA (p < 0.01). The increase in 17PGN was
      evident (p < 0.02), but the established significant p value was not reached. No
      differences for 17OHP, androstenedione and cortisol were found. The stimulated
      17PGN/17OHP ratio was significantly higher (p < 0.01) after GH, whereas the
      17OHP/androstenedione ratio was considerably lower, but the p value was < 0.02.
      No differences between pretreatment values with the control group androstenedione
      was found, whereas basal and stimulated posttreatment values of DHA and
      stimulated values of 17PGN were higher in patients after GH therapy than in
      control group B. No differences between the 2 control groups were found. In
      conclusion our study showed that adrenal steroid responsiveness to ACTH increases
      in Turner syndrome after long-term treatment with high GH doses. An increase in
      the number of ACTH adrenal receptors and/or a modulation of enzyme activities may
      be suggested. The positive or negative pharmacological implications of these data
      remain to be determined especially when taking into consideration the wide use of
      GH therapy in non-GH-deficient subjects.

PMID- 9568805
TI  - Growth failure in Prader-Willi syndrome is secondary to growth hormone
      deficiency.
AB  - Growth failure is a recognized feature of the Prader-Willi syndrome (PWS).
      Despite evidence that hypothalamic dysfunction accompanies the syndrome, the
      etiology of this growth failure remains controversial because most patients with
      PWS are obese. In order to contribute to resolution of this controversy, we
      performed a retrospective analysis of 16 obese and non-obese PWS children. GH
      deficiency was diagnosed in 12 of the 16 subjects and occurred independently of
      weight status. All of the non-obese subjects were GH deficient. Of the 4 GH
      sufficient children, 2 were moderately obese and 2 were morbidly obese. One of
      these children had clinical evidence of GH deficiency including a low IGF-1
      level. Only one of the children had evidence of GH deficiency and a normal IGF-1
      level, a pattern that could be attributable to obesity. We conclude that most
      short children with PWS have growth hormone deficiency and that this deficiency
      probably results from hypothalamic dysfunction.

PMID- 9568806
TI  - Effects of glucagon-like peptide 1 (7-36 amide) on glucose kinetics during
      somatostatin-induced suppression of insulin secretion in healthy men.
AB  - Glucagon-like peptide 1 (GLP-1) is known to stimulate insulin secretion and
      biosynthesis, but has also been shown to decrease insulin requirements in type 1
      diabetic subjects suggesting insulin-independent effects. To assess whether GLP-1
      exerts also direct effects on whole-body glucose metabolism, 6,6-D2-glucose
      kinetics were measured in 8 healthy volunteers receiving once GLP-1, once saline
      during hyperglycemic glucose clamping, while somatostatin with replacement
      amounts of insulin, glucagon and growth hormone was infused. Even though
      endogenous insulin secretion could not be blocked completely (increased plasma
      concentrations of C-peptide and proinsulin), somatostatin infusion resulted in
      stable insulin and glucagon plasma levels in both protocols (GLP-1 vs. placebo:
      NS). After 3 h of GLP-1 infusion, peripheral glucose disappearance significantly
      increased compared to placebo (p < 0.03) despite of somatostatin-induced
      suppression of insulin and glucagon secretion. Thus, GLP-1 infusion seems to have
      direct stimulatory effects on peripheral glucose metabolism in man.

PMID- 9568807
TI  - Irreversible increase of serum IGF-1 and IGFBP-3 levels in GnRH-dependent
      precocious puberty of different etiologies: implications for the onset of
      puberty.
AB  - In normal puberty, as well as in precocious puberty, serum GH, IGF-1 and IGFBP-3
      are increased as a consequence of the increase in sex hormone secretion. However,
      the effect of suppressing sex hormones on serum GH and IGF-1 in precocious
      puberty is controversial. On the other hand, the interest in the interaction
      between the GH-IGF-1 system and the hypothalamic-pituitary gonadal axis has been
      reinforced by experimental evidence which indicates that IGF-1 might be involved
      in the regulation of the onset of puberty. We have studied 11 girls with GnRH
      dependent precocious puberty (Gr1), before and during treatment with GnRH analog
      for 1.43+/-0.81 years, and 4 children (3 boys and 1 girl) with GnRH-dependent
      precocious puberty secondary to congenital adrenal hyperplasia (Gr2), before and
      during treatment with hydrocortisone (HC) alone for 0.32+/-0.23 years, and during
      combined treatment with GnRH analog, for 1.87+/-1.43 additional years. The
      etiology of precocious puberty in Gr1 was either idiopathic or associated with
      several brain lesions (hydrocephalia, hypothalamic hamartoma, suprasellar
      astrocytoma). During follow-up, clinical status as well as gonadotropin
      suppression, tested with the acute GnRH test, was checked every 3 months.
      Peptides and steroid hormones were determined by radioimmunoassay. Normal values
      for serum IGF-1 and serum IGFBP-3 were established in our laboratory from a
      population of 165 clinically controlled subjects, aged 0.5-15 years. In Gr1,
      treatment arrested breast development and blunted LH and FSH response to GnRH in
      all subjects. In Gr2, during HC treatment, all patients had a pubertal type of
      response to the acute GnRH test which was suppressed during combination
      treatment. In Gr1, serum IGF-1 SDS for chronological age (CA), but not IGFBP-3
      SDS CA, was significantly high before GnRH analog treatment (mean+/-SD 1.33+/
      1.84 and -0.68+/-1.55, p < 0.05 and p = NS, respectively). IGF-1 SDS CA remained
      high and IGFBP-3 SDS CA remained normal during treatment (1.34+/-2.0 and 0.73+/
      1.93). In Gr2, serum IGF-1 and IGFBP-3 SDS CA were high before treatment (3.11+/
      0.74 and 1.31+/-1.43, p < 0.02 and p < 0.05, respectively), and they remained
      high during HC or combined treatment. In the two groups, serum IGF-1 SDS BA and
      serum IGFBP-3 SDS BA levels were similar to control subjects before and during
      treatments. In Gr1, mean serum dehydroepiandrosterone sulfate (DS) was within
      prepubertal preadrenarche values but serum androstenedione (delta4) was
      significantly higher (6.35+/-3.45 nmol/l) than in our own normal control group
      (1.84+/-1.18, n = 20), both before and during treatment (p < 0.02). In Gr2, serum
      DS and serum delta4 were high before treatment but they decreased to prepubertal
      values during combined treatment. It is concluded that (1) the CNS maturational
      events which change the regulation of serum IGF-1 and IGFBP-3 are induced by the
      pubertal increase in sex steroids in a nonreversible way and (2) the high adrenal
      steroid levels present in CAH induce a nonreversible activation of the GH-IGF-1
      axis and of the GnRH pulse generator.

PMID- 9568808
TI  - Apparent functionality but impractical quantification of neurotensin receptors on
      human peripheral lymphocytes.
AB  - Neurotensin (NT), a neuromodulator, is also thought to play an immunomodulatory
      role. We sought to confirm the effects of NT on proliferation in human peripheral
      blood lymphocytes (PBLs; n = 10), to characterize the binding properties of the
      NT receptor using Scatchard analysis, and to measure NT receptors using blood
      volumes (50 ml) applicable to clinical investigation. Incubation of
      phytohemagglutinin-stimulated PBLs with NT (10[-10] to 10[-13] M) in the presence
      of 0.07% normal human serum (72 h at 37 degrees C) significantly enhanced
      proliferation (p < 0.001), which is consistent with PBLs possessing functional NT
      receptors. However, the various experimental conditions tested constantly yielded
      low specific NT binding to human PBLs, and hence Scatchard analysis was
      impossible for 50-ml blood samples. Our data confirm the existence of a link
      between NT and the immune system and support a physiological significance for
      this link. However, measurement of NT receptor binding in readily available cells
      proved unsuitable for clinical investigation.

PMID- 9568809
TI  - Relation of race, age, and sex hormone differences to serum leptin concentrations
      in children and adolescents.
AB  - We explored the effects of race, age, and sex hormones on the serum leptin
      concentrations in 203 white and 88 black children and adolescents (ages 9.3-20.5
      years). A significant sex by race interaction on serum leptin levels (p = 0.0301)
      was observed with lower serum leptin concentrations, adjusted for subscapular
      thickness and age, in black boys than in white boys. Girls had serum leptin
      levels that were on average 2.15 times those of boys (p < 0.0001). There was an
      age by sex interaction (p < 0.0001) with serum leptin concentrations decreasing
      in boys but not in girls with age. A strongly inverse relationship of serum
      testosterone levels with serum leptin levels in boys (p = 0.0067) appeared to
      explain this effect of age. In conclusion, the serum leptin concentration is
      slightly lower in black boys. A higher testosterone level in boys appears to
      account for an age-related decline in serum leptin in boys and the overall lower
      levels in boys than in girls.

PMID- 9568810
TI  - Isolated ACTH deficiency.
AB  - Isolated ACTH is a rare cause of secondary adrenocortical insufficiency. The
      diagnosis is made by the demonstration of low cortisol production with low plasma
      ACTH, absent adrenal responses to stimulation for pituitary or hypothalamus with
      intact adrenal response to exogenous ACTH, and normal secretory indices of other
      pituitary hormones. We conclude that the diagnosis of this condition may be
      difficult due to the varied clinical presentation and etiologies.

PMID- 9568811
TI  - Late development of resistance to bromocriptine in a patient with
      macroprolactinoma.
AB  - We report the case of a man with an invasive macroprolactinoma who developed
      resistance to bromocriptine to which he had previously responded satisfactorily
      for 5 years. Subsequently, hyperprolactinemia was controlled equally well with
      600 microg quinagolide daily and later with 4.5 mg cabergoline weekly. This
      observation suggests that a loss of dopamine receptors at the tumoral cell
      surface might be the mechanism underlying acquired resistance to bromocriptine.
      In addition, no tumor growth was observed over a 10-year follow-up, which
      virtually excludes a malignant transformation of the prolactinoma. This case
      emphasizes the need for close supervision of patients with macroprolactinoma,
      even after the serum prolactin concentration has been normalized by
      bromocriptine. It furthermore illustrates the usefulness of quinagolide and
      cabergoline when resistance to bromocriptine develops after a prolonged period of
      adequate response to this drug.

PMID- 9568812
TI  - The role of calcium, phosphorus and vitamin D metabolism in the development of
      secondary hyperparathyroidism.

PMID- 9568813
TI  - Is there a lesser hyperparathyroidism in diabetic patients with chronic renal
      failure?
AB  - Diabetic patients on dialysis have lower levels of parathyroid hormone (PTH);
      however, there is no data regarding PTH levels with different degrees of chronic
      renal failure (CRF). We compared 58 diabetic patients with different degrees of
      CRF with 268 non-diabetic patients with CRF (serum creatinine >1.2 mg/dl). In
      both groups, we investigated the main biochemical parameters together with plasma
      calcium, phosphorus, magnesium, PTH and calcitriol. Diabetic patients showed
      lower levels of PTH than non-diabetics (P=0.003). The differences were observed
      in patients with creatinine clearance <70ml/min. We also observed differences in
      phosphorus, magnesium and tubular resorption of phosphate. In the group of
      diabetic patients, serum glucose correlated inversely with PTH. Our study
      suggests that poor control of diabetes (hyperglycaemia) may play a role in the
      pathogenesis of the hypoparathyroidism observed in patients with diabetes and
      CRF.

PMID- 9568814
TI  - Does hypophosphataemia induce hypoparathyroidism in pre-dialysis patients?

PMID- 9568815
TI  - The effect of a high phosphorus diet on the parathyroid cell cycle.
AB  - High extracellular phosphorus directly increases parathyroid hormone (PTH)
      secretion and gene transcription. The present study evaluates the effect of high
      phosphorus diet on the parathyroid cell cycle in rats with normal renal function.
      Rats were divided into two groups, receiving either a high phosphorus diet (HPD,
      P=1.2%) or a normal phosphorus diet (NPD, P=0.6%). The dietary calcium content
      was 0.6% in both diets. Rats were pair fed and sacrificed on days 0, 1, 5, 10 and
      15 after initiation of the diet. The parathyroid glands were removed and
      parathyroid cells dispersed for evaluation of cell cycle and apoptosis by flow
      cytometry. Serum calcium, phosphorus, PTH and calcitriol were measured. As
      compared with NPD, the ingestion of a HPD resulted in an increased number of
      cells in the S phase of the cell cycle from day 1 to 10 (1.2+/-0.09% vs 0.6+/
      0.04% for day 1, 1.2+/-0.11% vs 0.6+/-0.06% for day 5 and 1.0+/-0.09% vs 0.5+/
      0.04% for day 10, P<0.01). By day 15, the percentage of cells in the S phase in
      NPD and HPD were not different. In the rats fed the HPD, serum PTH increased
      significantly from day 5 through 15 (P<0.01). Parathyroid cell apoptosis was
      minimal and unaffected by the diet. At day 15, the parathyroid gland size in HPD
      was increased by 27% as compared with NPD (P<0.05). This increase should be
      attributed to cell proliferation since parathyroid cell size remained unchanged.
      Serum calcitriol and calcium were not significantly different in the two groups.
      In HPD, an increase in serum phosphorus was observed only on day 1. The results
      show that an HPD results in the stimulation of the parathyroid cell cycle
      independently of changes in calcium and calcitriol.

PMID- 9568816
TI  - Effect of desferrioxamine and deferiprone (L1) on the proliferation of MG-63 bone
      cells and on phosphatase alkaline activity.
AB  - In the present work, we studied: (i) the effect of different doses of
      desferrioxamine and deferiprone on the proliferation of osteoblasts and the
      possible role of iron in this; and (ii) the effect of both chelators on the
      metabolic activity of these cells, using the quantification of alkaline
      phosphatase as an enzymatic marker of cellular activity or differentiation.
      Cellular proliferation was investigated at different concentrations of
      deferiprone and desferrioxamine, and the effect of the addition of iron citrate
      on this proliferation was measured. The production of alkaline phosphatase after
      incubation with deferiprone (150 and 300 microM) and desferrioxamine (20 and 100
      microM) was also studied. Cellular proliferation was completely inhibited with
      100 microM of desferrioxamine and 300 microM of deferiprone. In both cases, this
      effect was corrected by means of co-incubation with iron citrate. In the second
      phase, using the same dose that inhibited the proliferation, it was observed that
      after 24 h, both chelators slightly decreased alkaline phosphatase activity,
      while at 48 and 96 h they increased alkaline phosphatase activity. These results
      demonstrate that both desferrioxamine and deferiprone inhibit the proliferation
      of the osteoblast-like cell line MG-63; the effect seems to be related to the
      chelation of some fraction of available iron. In spite of the effect on bone cell
      proliferation, the chelators do not impair cellular activity.

PMID- 9568817
TI  - Biochemical markers of bone turnover in the diagnosis of renal osteodystrophy:
      what do we have, what do we need?

PMID- 9568818
TI  - Has double-phase MIBI scintigraphy usefulness in the diagnosis of
      hyperparathyroidism?
AB  - The usefulness of double-phase parathyroid technetium-99m-MIBI scintigraphy for
      the detection of hyperplastic parathyroid tissue has been described. The aim of
      the present study was to establish the effectiveness of this new technique in the
      morphological and functional assessment of parathyroid glands in patients with
      different types of hyperparathyroidism. We performed 99mTc-MIBI scintigraphy
      (MIBI) and neck ultrasonography in 38 patients with primary (n=16) or secondary
      (n=22) hyperparathyroidism. All patients underwent surgical neck exploration,
      removing a total of 84 parathyroid glands. Before and after surgery, blood intact
      parathyroid hormone (iPTH) was measured peripherally and in both the right and
      left internal jugular veins. In patients with primary hyperparathyroidism,
      ultrasonography showed one enlarged gland in 11 cases (69%), while MIBI was
      positive in 15 (94%) (including two ectopic glands). The sensitivity of MIBI
      (93%) was greater than that of ultrasonography (68%), with a similar specificity
      (100 and 97%, respectively). In patients with secondary hyperparathyroidism,
      there was a discrepancy between both imaging modalities in 29 glands (33%). The
      sensitivity of both techniques was similar (41 and 54%, respectively), with the
      same specificity (89%). There were more difficulties in detecting the upper than
      the lower pathological glands. MIBI reflected more accurately the functionality
      of the glands, and ultrasonography has a better correlation with the volume and
      weight. In conclusion, Tc-99m-MIBI scintigraphy is a good technique to identify
      parathyroid hyperfunctioning tissue in cases of primary hyperparathyroidism and
      to detect ectopic glands, but it does not give significantly better results than
      conventional ultrasonography in patients with secondary hyperparathyroidism.

PMID- 9568819
TI  - Epidemiology of renal osteodystrophy in Iberoamerica.

PMID- 9568820
TI  - High frequency of iron bone deposits in a Mexican population with renal
      osteodystrophy.
AB  - Renal osteodystrophy (ROD) is a multifactorial disease. Aluminium deposits have
      been implicated in its physiopathology but iron deposits have seldom been
      described. The purpose of this study was to investigate the presence of iron on
      the mineralization front, in 70 patients with ROD. Their mean age was 48+/-16
      years, 36 were female, 34 male, 55 were admitted on peritoneal dialysis (78.5%)
      and 15 to haemodialysis (21.5%), for a period of 28+/-22 months. A bone biopsy
      was obtained from each patient after double tetracycline labelling. Blood samples
      were also obtained at the time of bone biopsy. The histomophometric analysis was
      performed following the criteria of Sherrard et al., with slight modifications;
      beside the usual stains, aluminium, iron and amyloid stainings were done on all
      bone specimens. Biochemical findings were: Ca 8.8+/-0.9 mg/dl, P 6.1+/-1.5 mg/dl;
      total alkaline phosphatase 197+/-258; PTHm 4.9+/-4.05ng/ml (normal 0.4-0.7
      ng/ml), calcitonin 11+/-6 pg/ml (normal 1-26 pg/ml). Osteitis fibrosa was found
      in 31 patients (44.28%), mixed bone disease in two patients (2.28%); mild bone
      disease in 20 subjects (28.57%), adynamic bone lesion in 15 cases (21.42%) and
      osteomalacia in two patients (2.28%). Iron deposits were found on the
      mineralization front in 43 patients (61.4%); in 17, the percentage was <25 and,
      in 26, >25%. The iron deposits in the osteitis fibrosa group were highly
      significant (25/31). The aluminium deposit at the mineralization front was
      observed in eight patients (11.4%); in all but one, the percentage of this metal
      was <10%. Amyloid deposits were negative in all cases. The results show: (i) a
      Mexican population with ROD, present a highly significant incidence of siderosis
      on the bone mineralization front; (ii) in contrast, the aluminium deposits in
      this group of patients is lower than that reported in other series, and (iii) the
      spectrum of RO in this Mexican population is similar to that reported in other
      studies.

PMID- 9568821
TI  - Prevention, diagnosis and treatment of renal osteodystrophy in Spain. Preliminary
      results from a multicentre enquiry.
AB  - Prevention, diagnosis and treatment of renal osteodystrophy are continually
      evolving. We submitted a postal questionnaire to all Spanish dialysis centres,
      comprising 30 questions, with the aim of obtaining information about the current
      management of this entity in Spain. The answers from 171 centres, 63% of the
      total registered (10,724 patients), were analysed. The centres performed an
      annual average of nine calcium and phosphorus determinations, three for
      parathyroid hormone (PTH), 1.5 for aluminium and one for bone radiology. For
      these parameters, nephrologists consider ideal levels to be 10-10.5 mg/dl for
      calcium (53% of centres), 4.5-5.5 mg/dl for phosphorus (77%) and 120-150 pg/ml
      for iPTH (75%). The calcium concentration used in the dialysis fluids was found
      to be variable: 2% of the centres used 2 mEq/l, 44% used 2.5 mEq/l, 28% used 3
      mEq/l and 26% used 3.5 mEq/l. When using oral calcitriol, 82% of the centres do
      not change the calcium concentration in the dialysis fluids; this percentage
      falls to 51% when calcitriol administration is parenteral. In 78% of centres,
      vitamin D treatment was started when PTH was high, without taking into
      consideration the plasma calcium level. The dose varies; in 28% of the centres
      calcitriol pulse therapy was started when iPTH was >250 pg/ml; 52% when >500
      pg/ml and 16% when >750 pg/ml. Seventy one percent of the centres claim to use
      calcitriol in doses proportional to the severity of hyperparathyroidism. With
      regard to response to treatment, 78% of the centres wait for 6 months before
      considering a patient as a 'non-responder' and 80% of the centres would carry out
      parathyroidectomy only when iPTH is >750 pg/ml. The data collected from the
      enquiry show that there are important variations in some aspects related to
      current patient management in the different units in Spain. Diagnostic criteria
      are relatively homogeneous whereas the therapeutic guidelines are less uniform.

PMID- 9568822
TI  - The importance of hyperphosphataemia in the severity of hyperparathyroidism and
      its treatment in patients with chronic renal failure.

PMID- 9568823
TI  - How do we have to use the calcium in the dialysate to optimize the management of
      secondary hyperparathyroidism?

PMID- 9568825
TI  - Intermittent oral 1alpha-hydroxyvitamin D2 is effective and safe for the
      suppression of secondary hyperparathyroidism in haemodialysis patients. 1alphaD2
      Study Group.
AB  - Calcitriol and alfacalcidol are useful in suppressing parathyroid hormone (PTH)
      in haemodialysis patients, but hypercalcaemia and hyperphosphataemia are
      frequent. The vitamin D analogue, 1alpha-hydroxyvitamin D2 (1alphaD2), has a
      higher therapeutic index in animal models. Previously, 1alphaD2, 4 microg/day or
      4 microg/haemodialysis, lowered iPTH to the target range in 87.5% of 24
      haemodialysis patients with moderate to severe secondary hyperparathyroidism
      (plasma iPTH, 359-1521 pg/ml). The incidences of hypercalcaemia (serum Ca>2.8 mM)
      or hyperphosphataemia (serum P>2.23 mM) were low. Later, 10 of these patients
      were re-treated with 1alphaD2, initial dose, 10 microg, thrice weekly with
      haemodialysis. The iPTH was suppressed as readily, and there was no greater
      incidence of hypercalcaemia and hyperphosphataemia. Based on these data, a large,
      multicentre study is ongoing in California and Tennessee/Mississippi, using
      1alphaD2 in haemodialysis patients with iPTH >400 pg/ml. In this and the earlier
      studies, only calcium-based phosphate binders were used to control serum
      phosphorus. The initial dose, 10 microg thrice weekly with haemodialysis, is
      adjusted to maintain a target iPTH within the range of 150-300 microg/ml; the
      final dose range is 2.5-20 microg per haemodialysis. The protocol includes 8
      weeks of wash-out with no vitamin D, 16 weeks of open label treatment period with
      1alphaD2, and finally 8 weeks of randomized double blinded treatment with either
      continued 1alphaD2 or placebo. Forty two patients from California and 38 from
      Tennessee/Mississippi have completed 16 weeks of open label treatment. In
      California, iPTH declined from 832+/-95 pg/ml at baseline to 222+/-71 pg/ml at
      the nadir and to 477+/-117 pg/ml at week 16 of the treatment. In
      Tennessee/Mississippi, the iPTH declined from 977+/-65 pg/ml to 286+/-42 pg/ml at
      the lowest point and to 493+/-79 at the end of the treatment. Plasma iPTH reached
      or fell below the target range in 84% of the 80 patients completing open
      treatment. Asymptomatic hypercalcaemia (serum Ca>2.8 mM) increased from 0.3
      episodes/100 weeks during wash-out to 3.6 episodes/100 treated weeks in
      California and from 0 to 3.7 episodes in Tennessee/Mississippi. In California and
      Tennessee, the episodes of hyperphosphataemia (serum P>2.2 mM) increased from 5.0
      and 5.0 episodes per 100 patient/week during wash-out to 10.1 and 10.9
      episodes/100 treatment weeks, respectively, with 1alphaD2 treatment. There were
      no adverse events in association with 1alphaD2 treatment. Thus, oral 1alphaD2 is
      safe and highly effective for the treatment of secondary hyperparathyroidism.

PMID- 9568824
TI  - Is it possible to control hyperphosphataemia with diet, without inducing protein
      malnutrition?
AB  - Dietary intervention, phosphate (P) removal during dialysis and, especially,
      phosphate binders are current methods for the management of hyperphosphataemia.
      Ideally, the amount of P absorbed from the diet should equal the amount of P
      removed during dialysis, and this must occur in the context of an adequate
      protein intake. We evaluated the relationship between P intake and protein intake
      in 60 stable chronic uraemic patients (mean age 55+/-15 years, 25% diabetics, 68%
      males) on standard 4 h haemodialysis. The dietary counselling was relatively free
      for protein and calories. Nutrient intake was recorded during a 5 day period, and
      average daily ingestion of P and proteins was calculated using a computerized
      diet analysis system. A highly significant correlation was observed between
      protein and P intake. The mean daily ingestion of P and proteins was 998+/-316 mg
      and 64+/-19 g (1+/-0.4 g/kg/day), respectively. For an optimal protein diet of 1
      1.2 g/kg/day, the P intake was 778-1444 mg. The amount of P removed by
      haemodialysis, extrapolated to an average week, is 250-300 mg/day. Since
      approximately 40% of P ingested is absorbed from the gut by uraemic patients
      treated with intestinal P binders, 750 mg of P intake should be the critical
      value above which a positive balance of P may occur. This value corresponds to a
      protein intake of 45-50 g per day (>0.8 g/kg body weight/day for a 60 kg
      patient). In patients undergoing standard chronic haemodialysis, a neutral P
      balance is difficult to achieve, despite phosphate binder therapy, when protein
      intake is >50 g. Additional protein restriction, in order to obtain a neutral
      balance, may impose the risk of protein malnutrition.

PMID- 9568826
TI  - Vitamin D receptor gene (VDR) polymorphisms: effect on bone mass, bone loss and
      parathyroid hormone regulation.

PMID- 9568827
TI  - Prevention of aluminium exposure through dialysis fluids. Analysis of changes in
      the last 8 years.
AB  - Despite extensive measures to control aluminium exposure, chronic and acute
      episodes of aluminium intoxication still occur. The objective of this study was
      to analyse the changes in the aluminium content of dialysis fluid and the effect
      on serum aluminium in different dialysis centres in Spain in the last 8 years.
      For this purpose, the aluminium content in dialysis fluid and serum samples
      (N=5609) from 17 dialysis centres was analysed for >8 years (from the last
      quarter of 1988 to 1996). In that period of time, the percentage of dialysis
      fluid samples with acceptable concentrations of aluminium (<2 microg/l) increased
      from 0% in 1988 to 80% in 1996. The percentage of dialysis fluid samples with
      high aluminium levels (>6 microg/l) ranged between 37.5% in 1988 and 2.3% in
      1996. The improvement in the quality of the dialysis fluid resulted in lower
      values of serum aluminium. The percentage of serum samples with low aluminium
      (<20 microg/l) increased from 16.5% in 1988 to 54.2% in 1966. The mean serum
      aluminium correlated with the mean dialysis fluid aluminium (r=0.55, P<0.001). A
      higher correlation was found when the aluminium in dialysis fluid ranged between
      4 and 10 microg/l (r=0.802, P<0.001), and no correlation was found when the
      aluminium in dialysis fluid was <4 microg/l. Even taking into account that the
      dialysis fluid is not the only source of aluminium for dialysis patients, our
      study clearly demonstrated a close relationship with the serum aluminium content.
      Therefore, we must emphasize the necessity for controlling the aluminium content
      in dialysis fluid more often than is done at present.

PMID- 9568828
TI  - Bone disease in hypercalciuria: a new form of osteodystrophy?

PMID- 9568829
TI  - Are plasma 1,25-dihydroxyvitamin D3 concentrations appropriate after successful
      kidney transplantation?
AB  - We studied 28 patients with parathyroid hormone (PTH) concentrations >65 pg/ml
      immediately prior to kidney transplant and who had stable allograft function with
      serum creatinine <2 mg/dl. After 12-18 months of transplantation, biochemical
      parameters (including 25-hydroxy- and 1,25-dihydroxy-vitamin D3) were studied.
      Patients were divided into three groups according to their PTH concentrations.
      Patients with renal transplant were compared with 50 healthy subjects and 20
      patients with primary hyperparathyroidism. The mean 1,25-dihydroxy-vitamin D3
      concentration of the transplant patients did not differ from the controls, but
      was lower than in patients with primary hyperparathyroidism. Using univariate
      linear regression analysis, 1,25-dihydroxy vitamin D3 correlated positively with
      PTH (P=0.008) and serum calcium (P=0.0015), and inversely with creatinine
      clearance (P=0.01). However, it did not correlate significantly with serum
      phosphorus. Our data suggest that renal transplant recipients may have an
      inappropriate production of 1,25-dihydroxy vitamin D3; suboptimal allograft
      function may be a major limiting factor.

PMID- 9568830
TI  - Parathyroid function in long-term renal transplant patients: importance of pre
      transplant PTH concentrations.
AB  - Lack of resolution of hyperparathyroidism after long-term renal transplantation
      is common. The relative roles of the graft function attained and the degree of
      pre-transplant hyperparathyroidism have not been established. Intact parathyroid
      hormone (iPTH) and several clinical parameters were studied before and 68.6+/
      26.8 months (range: 30-124) after renal transplantation in 62 patients (20
      females/42 males) with good renal function (creatinine <2 mg/dl). iPTH decreased
      from 214+/-229 pre-transplantation to 116+/-70 pg/ml post-transplantation
      (P<0.01). However, only 22.6% of patients had PTH concentrations in the normal
      range, and values greater than twice the upper normal limit were not uncommon
      (27.4%). Of the many variables analysed, creatinine (r=0.43; P=0.001) and pre
      transplant PTH (r=0.31; P=0.02) significantly correlated with post-transplant
      PTH. After selecting patients with serum creatinine <1.5 mg/dl (n=46), pre
      transplant PTH emerged as the more important predictor of post-transplant PTH
      (r=0.58; P<0.0001). After controlling for creatinine, the partial correlation was
      r=0.53, P<0.0001. We concluded that spontaneous resolution of hyperparathyroidism
      after renal transplantation is uncommon. In addition, the magnitude of pre
      transplant hyperparathyroidism and the renal function determine the long-term
      post-transplant parathyroid function.

PMID- 9568831
TI  - Time course and functional correlates of post-transplant aluminium elimination.
AB  - Urinary excretion of aluminium after a successful transplant can reverse pre
      transplant aluminium intoxication. We have evaluated the time course of urinary
      aluminium excretion and its correlation with several parameters of renal function
      and mineral metabolism in 49 patients (33 men and 16 women) with a wide range of
      pre-transplant serum aluminium concentrations, performing sequential
      determinations at pre-transplant time and at 7, 30, 60, and 90 post-transplant
      days. Mean serum aluminium at pre-transplant was 54.5+/-46.8 microg/l decreasing
      progressively to 28.7+/-24.4 microg/l at 90 days (P<0.0002), paralleling the
      decrease in serum creatinine. Urinary aluminium decreased from 63.0+/-77.9 to
      52.4+/-55.9 microg/l at 90 days (P<0.0001). The maximum urinary
      aluminium/creatinine was 1.8+/-2.7 at 7 days and was associated with the greatest
      fractional excretion of sodium (4.7+/-5.1%), and the lowest tubular reabsorption
      of phosphate (55.7+/-25.1%). The fractional excretion of aluminium was also
      greatest at day 7 (1.1+/-0.9%) when serum creatinine was still elevated (3.6+/
      2.3 mg/dl). At each period of time after transplantation fractional excretion of
      aluminium was similar in all patients despite disparate serum aluminium
      concentrations. Fractional excretion of aluminium was highest in those patients
      who developed post-Tx acute tubular necrosis (0.7+/-0.5 vs 1.5+/-1.0%, P=0.008).
      We found a direct positive correlation (r=0.43; P<0.002) between urinary
      aluminium and urinary phosphate. Basal levels and sequential changes in serum
      PTH, calcium, and phosphate did not correlated with fractional excretion of
      aluminium. These findings suggest: (i) urinary aluminium remains elevated during
      prolonged periods after transplant and is probably a marker of pre-transplant
      tissue aluminium accumulation; (ii) post-transplant fractional excretion of
      aluminium seems to correlated positively with other evidences of renal tubular
      dysfunction. Early post-transplant tubular malfunction could significantly
      enhance urinary aluminium elimination.

PMID- 9568833
TI  - The implications of metabolic acidosis in intensive care unit patients.

PMID- 9568832
TI  - What are the bone lesions in patients with more than four years of a functioning
      renal transplant?

PMID- 9568835
TI  - Individual kidney function in atherosclerotic nephropathy.

PMID- 9568834
TI  - Susceptibility genes for end-organ damage. New strategies to understand diabetic
      and hypertensive nephropathy.

PMID- 9568836
TI  - Choices of long-term immunosuppression in renal transplantation: balancing the
      benefits and risks.

PMID- 9568837
TI  - What is the most appropriate strategy to monitor functional iron deficiency in
      the dialysed patient on rhEPO therapy? Merits of percentage hypochromic red cells
      as a marker of functional iron deficiency.

PMID- 9568838
TI  - What is the most appropriate strategy to monitor functional iron deficiency in
      the dialysed patient on rhEPO therapy? Measurement of hypochromic red blood cells
      is not the first line procedure to identify the patient with iron deficiency.

PMID- 9568839
TI  - Transatlantic view.

PMID- 9568840
TI  - Some trends in chronic renal replacement therapy in Australia and New Zealand,
      1997.
AB  - The incident and prevalent rate of renal failure treatment shows a trend towards
      an older patient population, with more diabetics and non-Caucasoid patients. A
      concurrent increase in comorbid risk factors (mainly vascular) has influenced
      outcome results. Comparison of outcome should include allowance for the patient
      mix, and the trend to a trial of dialysis. Most patients have been dialysed at
      home or at free-standing (satellite centres). The dialysis prescription for
      haemodialysis has shown a trend to faster blood flow, longer hours, and more
      'biocompatible' cellulose membranes. Most peritoneal dialysis has disconnection
      systems, and increasing daily volume of dialysate.

PMID- 9568841
TI  - Evolution of renal replacement therapy in Central and Eastern Europe 7 years
      after political and economical liberation. Central and Eastern Europe Advisory
      Board in Chronic Renal Failure.
AB  - PURPOSE OF THE STUDY: The conditions of renal replacement therapy (RRT) were very
      poor in the countries located in Central and Eastern Europe (CEE) when they were
      members of the so-called 'socialist bloc'. The aim of the present analysis was to
      document the impact of the socioeconomic changes on dialysis therapy in the CEE
      countries. DESIGN: This was a special survey with the participation of 12 CEE
      countries, with data obtained through national registries (with the exception of
      Russia). RESULTS: During the period 1990-1996 the number of haemodialysis units
      increased by 56% and the number of centres performing peritoneal dialysis by
      296%. The number of patients increased respectively by 78% (haemodialysis) and
      306% (peritoneal dialysis). The percentage of patients with diabetic nephropathy
      and elderly patients rose dramatically during this period. One of the main
      reasons of such expansion was the rapid development of peritoneal dialysis
      programmes in the majority of the CEE countries. The introduction of modern
      haemodialysis machines and a wider choice of different dialysers and concentrates
      permitted individualization of dialysis procedures. These points and the wider
      use of erythropoietin had a positive influence on quality of life and treatment
      outcome. There was also a notable increase in the number of transplant centres,
      but less so of the number of transplanted patients. CONCLUSION: Renal replacement
      therapy experienced a major expansion in the CEE countries. Despite the progress
      achieved, the level of RRT is not yet completely satisfactory in most CEE
      countries.

PMID- 9568842
TI  - Struggling to deliver ESRD therapy in developing nations.

PMID- 9568843
TI  - Mechanisms and clinical significance of cell volume regulation.
AB  - A wide variety of factors challenge constancy of cell volume. Alterations of cell
      volume activate diverse cell volume regulatory mechanisms including ion
      transport, osmolyte accumulation, metabolism and expression of appropriate genes.
      A wealth of cellular signalling pathways link cell volume to the respective
      regulatory mechanisms. Cell volume emerges as a pathophysiologically important
      parameter in several diseases including diabetes mellitus, uraemia, hepatic
      insufficiency and hypercatabolic states. The role of altered cell volume in
      disease is a challenge which requires more experimental research and clinical
      investigation.

PMID- 9568844
TI  - Effects of vascular endothelial growth factor (VEGF)/vascular permeability factor
      (VPF) on haemodynamics and permselectivity of the isolated perfused rat kidney.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) or vascular permeability
      factor (VPF) is a selective mitogen for endothelial cells; it increases
      microvascular permeability and has been shown to relax isolated canine coronary
      arteries by an endothelium-dependent mechanism. In many tissues VEGF/VPF is
      expressed after an appropriate stimulus, mostly hypoxia. In the kidney VEGF/VPF
      is constitutively expressed in glomerular podocytes and epithelia of collecting
      duct. Glomerular and peritubular capillary endothelia also constitutively express
      specific VEGF receptors. The in vivo function of renal VEGF/VPF is unknown.
      METHOD: In the present study the effects of human recombinant VEGF165 on renal
      haemodynamics and glomerular permselectivity was investigated in the isolated
      perfused kidney of the rat. RESULTS: In kidneys preconstricted by noradrenaline
      (NA 1.5 x 10(-7) mol/l) VEGF/VPF (155 pmol/l) caused an almost complete return of
      renal perfusion flow rate to pre-NA values (before NA 113 +/- 4%, after NA 100%,
      15 min with VEGF/VPF 111 +/- 4%). Shortly after VEGF/VPF administration VEGF/VPF
      induced relaxation commenced, and became significant after 2 min (15 min with
      VEGF/VPF vs without VEGF/VPF 111 +/- 4% vs 103 +/- 2%; P<0.05). In the presence
      of the NO-synthase inhibitor N(W)-nitro-L-arginine (L-NNA; 5 x 10(-5) mol/l)
      VEGF/VPF caused only small, transient relaxations (before NNA 109 +/- 5%, after
      NNA 100%, 15 min with VEGF 95 +/- 2%). The cyclooxygenase inhibitor diclofenac
      failed to inhibit the relaxing activity of VEGF/VPF (before NA 119 +/- 4%, after
      NA + diclofenac 100%, 15 min with VEGF/VPF 123 +/- 5%). VEGF demonstrated no
      significant increase in renal protein excretion rate (after NA pretreatment (=
      100%): 12.5 min with VEGF/VPF vs without VEGF/VPF: 119 +/- 10% vs 132 +/- 11%,
      n.s.) (after NNA pretreatment (= 100%) 12.5 min with VEGF/VPF vs without VEGF/VPF
      94 +/- 5% vs 96 +/- 4%; n.s.) or clearance quotient of albumin. Glomerular
      filtration rate was not influenced by VEGF/VPF in kidneys pretreated with NA
      (before NA 105 +/- 5%, after NA 100%, 12.5 min with VEGF/VPF 94 +/- 2%) or with
      NNA (before NNA 107 +/- 6%, after NNA 100%, 12.5 min with VEGF/VPF 96 +/- 2%).
      Fractional glucose and fractional sodium excretion showed flow-dependent changes.
      CONCLUSION: VEGF/VPF can contribute to the relaxing capacity of the renal
      vasculature. This relaxation is partly mediated by the NO/endothelium-derived
      relaxing factor (EDRF) pathway. In the isolated perfused rat kidney the
      glomerular permeability for albumin is not affected by VEGF/VPF.

PMID- 9568845
TI  - Overexpression of extracellular matrix proteins in renal tubulointerstitial cells
      by platelet-activating-factor stimulation.
AB  - BACKGROUND: One common feature of renal diseases is the development of
      interstitial fibrosis, but the mechanism of this process remains undefined. We
      hypothesized that platelet-activating factor (PAF), a classical acute
      inflammatory mediator involved in the pathogenesis of renal damage, acts on renal
      tubulointerstitial cells, contributing to the development of fibrosis. For this
      reason we evaluated the effect of PAF on matrix regulation and cell-growth
      related events in tubulointerstitial cells. METHODS: In vitro studies were
      conducted with two tubulointerstitial cell lines: renal tubuloepithelial cells
      (NRK 52E) and interstitial fibroblasts (NRK 49F). The effect of PAF on
      extracellular matrix gene expression was determined by Northern blot. Fibronectin
      synthesis was quantified by metabolic labelling and immunoprecipitation. Cell
      growth changes were evaluated by fluorescence-activated cell-sorting analysis
      (cell cycle and size) and total protein content by 3[H]leucine incorporation.
      RESULTS: In renal tubuloepithelial cells and interstitial fibroblasts, PAF
      increased fibronectin mRNA expression. PAF-effect on the expression of collagen
      genes differed depending on the cell type studied. In tubuloepithelial cells
      there was an increase in type I and IV collagen mRNA levels, while only type I
      collagen was increased in fibroblasts. The overexpression of matrix proteins
      induced by PAF was completely blocked by preincubation of cells with the PAF
      receptor antagonist, BN52021. The PAF-induced upregulation of fibronectin
      expression was correlated with the increase in fibronectin synthesis. These
      effects were not associated with an increase in hyperplasia (characterized by
      changes in cell cycle) either in tubuloepithelial cells or in interstitial
      fibroblasts. Moreover, PAF did not induce tubular hypertrophy (changes in protein
      content and cell size). CONCLUSIONS: Our data suggest that PAF could be a
      mediator involved in extracellular matrix accumulation and, therefore,
      participate in the formation of renal interstitial fibrosis.

PMID- 9568846
TI  - Tubuloglomerular feedback and prolonged ACE-inhibitor treatment in the
      hypertensive fawn-hooded rat.
AB  - BACKGROUND: The spontaneously hypertensive fawn-hooded (FHH) rat develops severe
      glomerulosclerosis with ageing. The afferent arteriolar resistance is low,
      resulting in a strongly elevated glomerular capillary pressure (P(GC)). METHODS:
      Afferent arteriolar resistance is under the control of the tubuloglomerular
      feedback (TGF) system, and we studied whether young FHH rats, i.e. at a stage
      when only mild glomerulosclerosis was present, have diminished TGF
      responsiveness. RESULTS: Maximum TGF-mediated decreases in stop-flow pressure in
      response to late proximal perfusion with artificial tubular fluid were 9.0 +/-
      1.0 mmHg, a value not different or even slightly lower than observed in normal
      rats. P(GC) was 59.9 +/- 1.2 mmHg and the estimated P(GC) at half-maximal
      activation of the TGF system (operating P(GC)) was 54.5 +/- 0.8 mmHg at 11 weeks
      of age (n = 11), a value higher than observed in normal rats. The second question
      of the present study concerns the effect of chronic angiotensin-I-converting
      enzyme inhibitor (ACE-i) administration on P(GC). ACE-i, by reducing angiotensin
      II (Ang II) availability, diminishes TGF responsiveness, which would offset the
      beneficial effect on P(GC) under normal flow conditions to the macula densa.
      Maximum TGF responses were 8.9 +/- 1.0 and 17.5 +/- 1.5 mmHg in 11- and 26-week
      old rats that had been treated with the ACE-i lisinopril in the drinking water
      started when the animals were 7 weeks of age. P(GC) was 44.3 +/- 1.2 (n = 9) and
      operating P(GC) was 40.1 +/- 1.6 mmHg (n = 9) at 11, values significantly lower
      than in untreated rats. Values remained lower in the 26-week-old treated animals
      and were 40.9 +/- 0.8 and 32.6 +/- 1.1 mmHg. CONCLUSIONS: (1) the TGF system in
      this model of spontaneous hypertension and glomerulosclerosis is intact, despite
      the fact that the FHH rat has a characteristically low afferent arteriolar
      resistance as compared to other hypertensive rats; (2) the rat displays a normal
      or even enhanced function of the TGF system following prolonged administration of
      the ACE-i lisinopril. The latter finding indicates that the reduction of P(GC)
      achieved by the ACE-i is not offset by a concomitant attenuation of TGF function.

PMID- 9568847
TI  - Natriuretic effect of adenosine A1-receptor blockade in rats.
AB  - BACKGROUND: Many effects of adenosine on renal function have been identified. The
      development of adenosine receptor blockers has made it possible to identify which
      of these effects are exerted by endogenous adenosine. At least four adenosine
      receptor subtypes, denoted A1, A2a, A2b, and A3 are currently known. In the
      present study the selective A1 receptor blocker 1,3-dipropyl-8[2-(5,6-epoxy)
      norbanyl] xanthine (CVT-117) was used to assess the effect of A1 activation by
      endogenous adenosine on renal function in rats. METHODS: Clearance studies were
      performed before and after administration of 0.1 mg/kg and 0.8 mg/kg of CVT-117
      in separate groups of rats and before and after administration of vehicle in time
      control rats. Measurements of heart rate before and after administration of
      exogenous adenosine confirmed effective A1 receptor blockade. RESULTS: At both
      the lower and higher doses, A1 receptor blockade with CVT-117 increased
      fractional sodium excretion and urine flow rate without altering GFR. The
      increase in sodium excretion following A1 blockade was not accompanied by
      increases in the excretion of phosphate or potassium. CONCLUSION: These results
      show that endogenous adenosine promotes sodium retention by activation of A1
      receptors.

PMID- 9568848
TI  - Detrimental effect of dietary sodium and beneficial effect of dietary magnesium
      on glomerular changes in cyclosporin-A-treated spontaneously hypertensive rats.
AB  - BACKGROUND: Cyclosporin A (CsA) causes renal magnesium wasting, hypertension, and
      occasionally irreversible renal damage. We examined the effect of dietary sodium
      and magnesium on renal histology in spontaneously hypertensive rats (SHR)
      receiving CsA. METHODS: Forty-six 8-week-old SHR were divided into six groups and
      given different dietary levels of sodium (low 0.3%, high 2.6%) and magnesium (low
      0.2%, high 0.6%). Low-dose CsA (5 mg/kg/d) was given subcutaneously for 6 weeks
      in four groups. Systolic blood pressure, serum creatinine, degree of proteinuria,
      and renal tissue CsA and calcium concentrations were determined. Kidney wet
      weight to total body-weight ratio was calculated as an index of renal
      hypertrophy. Renal histological alterations were scored according to glomerular
      changes: 100 glomeruli were assigned for severity of change a score from 0 to 3.
      The number of affected glomeruli was multiplied by the damage score to obtain a
      damage index. RESULTS: In the CsA-treated high-sodium diet group systolic blood
      pressure and glomerular damage index were increased, and renal hypertrophy was
      the most common. These changes were prevented by oral magnesium supplementation.
      The glomerular damage index correlated positively with increases in systolic
      blood pressure, serum creatinine, proteinuria, and renal calcium concentration.
      CONCLUSIONS: Dietary sodium enhanced CsA-induced functional and morphological
      renal changes in SHR and aggravated hypertensive renal arteriolar and glomerular
      lesions. Dietary magnesium supplementation protected against the deleterious
      effects of sodium and CsA.

PMID- 9568849
TI  - Radiocontrast-induced DNA fragmentation of renal tubular cells in vitro: role of
      hypertonicity.
AB  - BACKGROUND: Radiocontrast-induced nephropathy is a clinically important
      complication of invasive cardiological procedures. It has been associated with
      DNA fragmentation of renal tubular cells, which is a hallmark feature of
      programmed cell death (apoptosis). We investigated the mechanism of this DNA
      fragmentation in an in vitro model of radiocontrast cytotoxicity on renal
      epithelial cells. METHODS: Madin Darby canine kidney (MDCK) cell monolayers were
      incubated (for 2-8 h) with isoiodine doses (37-111 mg iodine/ml) of the highly
      hyperosmolal, ionic radiocontrast agent diatrizoate or of the less hyperosmolal,
      non-ionic substance iopamidol. Mannitol, urea, and NaCl control media of
      corresponding hyperosmolality were used to evaluate the contribution of
      hypertonicity, hyperosmolality and/or ionic strength to radiocontrast toxicity.
      DNA fragmentation was assessed using fluorescence-activated cell sorting (FACS),
      agarose gel electrophoresis and terminal deoxynucleotidyl transferase-mediated
      deoxyuridine nick end labelling (TUNEL), cell morphology was analysed in Giemsa
      stained cytospins. RESULTS: Diatrizoate induced concentration- and time-dependent
      DNA fragmentation of MDCK cells which was associated with morphological signs of
      apoptosis. Cycloheximide (1 microg/ml) did not prevent diatrizoate-induced DNA
      fragmentation, indicating that it is not dependent on protein synthesis.
      Diatrizoate-mediated cell death was associated with cell detachment from the
      tissue culture matrix. However, the DNA fragmentation is not a consequence of
      cell detachment since the prevention of cell attachment on agarose-coated dishes
      induced significantly less DNA fragmentation than diatrizoate. Iopamidol caused
      no detectable DNA breakdown. In contrast, hypertonic mannitol and sodium
      chloride, but not hyperosmolal urea, induced DNA fragmentation in MDCK cells,
      albeit less than diatrizoate. CONCLUSIONS: The DNA fragmentation of MDCK cells
      induced by diatrizoate is related to its hypertonicity in this in vitro model of
      radiocontrast cytotoxicity. Nuclear disintegration with subsequent cell death may
      contribute to the pathophysiology of radiocontrast-induced nephropathy,
      particularly in the hypertonic/hypoxic environment of the renal medulla. The
      present results underscore the importance of avoiding hyperosmolal urine states
      in patients at high risk of radiocontrast-induced nephropathy.

PMID- 9568850
TI  - Tissue-type plasminogen activator activity in HIV-associated HUS.
AB  - BACKGROUND: In children, haemolytic uraemic syndrome (HUS) is associated with
      high plasma plasminogen activator inhibitor type 1 (PAI-1), which may contribute
      to the persistence of renal glomerular and arteriolar thrombi. HUS has been
      described in HIV-infected patients, but the pathophysiology of HUS in these
      patients is poorly understood. The aim of the study was to investigate plasma
      fibrinolytic activity in 18 patients with HIV-associated HUS. METHODS: We
      measured tissue type plasminogen activator (t-PA) and PAI-1 activities in the
      plasma of 18 HIV-infected patients with biopsy-proven HUS (HIV+/HUS+) and 48 HIV
      infected patients without HUS (HIV+/HUS-). RESULTS: Patients with HUS had a
      significantly higher serum creatinine, a lower platelet count and an increased
      incidence of cytomegalovirus (CMV) infection (72% of patients HIV+/HUS+, vs 25%
      of patients HIV+/HUS-). Unexpectedly, plasma PAI-1 activity was similar in both
      groups. However, t-PA activity was significantly higher in HUS cases (11.5 vs 4.5
      U/ml, P=0.001). Patients with CMV infection, with or without HUS, had
      significantly increased t-PA level (P=0.01). Multivariate analysis identified
      high t-PA (RR=9.21) and CMV infection (RR=3.36) as risk factors for HUS.
      CONCLUSION: This study provides evidence that HIV-infected patients with HUS have
      high plasma t-PA activity. PAI-1 plasma activity is not significantly increased,
      as opposed to non-HIV-associated HUS. Thus, in the setting of HIV infection, HUS
      cannot be attributed to decreased fibrinolytic activity.

PMID- 9568851
TI  - Rifampicin-induced acute renal failure: a series of 60 patients.
AB  - BACKGROUND: Since 1971, 55 case-reports of rifampicin-induced ARF have been
      published, but systematic data on this condition are not available, in view of
      the disparate nature of the observations. METHODS: We retrospectively assessed
      prevalence, clinical and biochemical features, and prognostic factors of 60
      consecutive cases (41 males/19 females, age 22-68 years), who were admitted to
      the Iasi Dialysis Centre from 1987 to 1995 for acute renal failure (ARF)
      following re-treatment with rifampicin. RESULTS: The clinical appearance
      consisted mainly of gastrointestinal and 'flu-like' symptoms and clinical signs
      of intravascular haemolysis (the latter in 17% of cases). Frequent laboratory
      findings were anaemia (96% of cases), leukocytosis (63%), and thrombocytopenia
      (50%). Severe anaemia was associated with marked haemolysis (25% cases),
      thrombocytopenia, longer anuria, and slower rate of renal function recovery.
      Signs of hepatic injury were found in 25% of patients, but it did not seem to
      affect the outcome of renal function. Prognostic factors in post-rifampicin ARF
      proved to be the following: the duration of the anuric phase (correlated with the
      number of dialysis sessions and with the rate of decrease of azotaemia) and the
      severity of the immunological abnormalities and inflammatory syndrome
      (haemolysis, leukocytosis, hypergammaglobulinaemia). Post-rifampicin ARF
      accounted for 16.6% of all ARF cases hospitalized in our Centre during the
      studied period. Its clinical course was favourable; the mortality rate was only
      1.6% (1 case), compared to a 20% general mortality rate among all ARF patients.
      Full recovery of renal function was achieved in 40% and 96% of patients, 30 and
      90 days respectively from onset. CONCLUSIONS: ARF after treatment with rifampicin
      is not an uncommon condition, especially when tuberculosis prevalence is high,
      but renal prognosis is usually favourable. Thrombocytopenia, immune haemolytic
      anaemia, and intravascular haemolysis are frequent complications which are
      associated with a more severe renal injury.

PMID- 9568852
TI  - Abnormal IgA glycosylation in Henoch-Schonlein purpura restricted to patients
      with clinical nephritis.
AB  - BACKGROUND: Glomerular deposition of IgA1 is a common feature of Henoch-Schonlein
      purpura, and is indistinguishable from that seen in IgA nephropathy. Serum IgA1
      is abnormally O-glycosylated in IgA nephropathy, and this may contribute to
      mesangial IgA1 deposition and the development of glomerular injury. This altered
      O-glycosylation of IgA1 can be detected by its increased binding to the lectin
      Vicia villosa. METHODS: To investigate whether IgA1 is abnormally glycosylated in
      Henoch-Schonlein purpura, the binding of Vicia villosa lectin to serum IgA1 was
      studied in the following subject groups: IgA nephropathy; adults and children
      with Henoch-Schonlein purpura and nephritis; children with clinically diagnosed
      Henoch-Schonlein purpura but no renal involvement; adults and children with non
      IgA associated glomerulonephritis; and matched controls. RESULTS: The abnormality
      of lectin binding seen in IgA nephropathy was also found in both adults and
      children with Henoch-Schonlein purpura with nephritis. However, the lectin
      binding of serum IgA1 from children with Henoch-Schonlein purpura lacking renal
      involvement did not differ from controls, and similarly, no abnormality of lectin
      binding was seen in patients with non-IgA associated glomerulonephritis.
      CONCLUSIONS: These data indicate that the abnormality of IgA1 O-glycosylation
      seen in IgA nephropathy is also found in Henoch-Schonlein purpura, but only in
      those subjects with renal involvement, while IgA1 O-glycosylation is normal in
      patients with other forms of renal disease. These findings lend strong support to
      a role for altered IgA1 O-glycosylation in the pathogenesis of IgA-associated
      glomerular disease.

PMID- 9568853
TI  - Anti-glomerular basement membrane (GBM)-antibody-mediated disease with normal
      renal function.
AB  - BACKGROUND: This study compared the clinical and laboratory characteristics of
      patients with anti-glomerular basement membrane (GBM) disease and normal renal
      function, with those of patients with anti-GBM disease where there was renal
      impairment. METHODS: The medical records of the 14 patients who had presented
      with anti-GBM disease to our hospital in the past 20 years were reviewed.
      RESULTS: Five (36%) had a normal serum creatinine or creatinine clearance at
      presentation. Other features were haemoptysis (2/5, 40%), macroscopic haematuria
      (2/5, 40%) or systemic symptoms (1/5, 20%). All five (100%) had some degree of
      haematuria, four (80%) had proteinuria of at least 1 g/day, and none was
      hypertensive. Anaemia, a raised WCC, or elevated ESR (> 35 mm/h) occurred less
      often than in patients with impaired renal function (P<0.05). Two of the five
      (40%) with normal renal function had circulating anti-GBM antibodies, which were
      present at low or moderate levels; but seven of the nine with renal impairment
      (77%) had circulating antibodies, with high levels in five. Renal biopsies from
      patients with normal renal function were normal (1/5, 20%), showed mesangial
      proliferation (4/5, 80%) or had more than 20% glomeruli sclerosed (1/5, 20%).
      Complement deposition was present in 2/4 biopsies (50%). The kidneys from
      patients with renal impairment had crescents in more than 50% glomeruli (9/9,
      100%), and four had more than 20% glomeruli sclerosed (44%). All four kidneys
      from patients with renal impairment that were examined had complement deposits
      (100%). Treatment was identical in both groups; patients with normal renal
      function were followed for a median of 48 months, and those with renal impairment
      for 180 months. There were no further episodes of haemoptysis, haematuria, or
      other symptoms of relapse in either group. All five patients with normal renal
      function are alive, and the serum creatinine is less than 0.2 mmol/l in all
      (100%), but haematuria persists in one (20%), and proteinuria >1 g/day in two
      (40%). Eight of the nine (89%) patients with impaired renal function survive, but
      all are currently being dialysed or have had a renal transplant. CONCLUSION:
      Patients with anti-GBM disease with normal renal function are not uncommon, and
      often have a good prognosis. There is less renal damage, possibly because of
      lower levels of circulating anti-GBM antibodies and less glomerular complement
      deposition.

PMID- 9568854
TI  - Contrasting renal effects of nicotine in smokers and non-smokers.
AB  - BACKGROUND: Cigarette smoking is associated with acute increase in arterial
      pressure due to systemic vasoconstriction and decreased skin and coronary blood
      flow. Virtually all cardiovascular effects of cigarette smoking are due to
      nicotine. However, whether nicotine also affects the renal circulation and
      function in humans is at present unknown. METHODS: In the current study the acute
      effects of a 4-mg nicotine gum on arterial pressure, heart rate as well as renal
      haemodynamics and function were assessed in non-smokers and chronic smokers.
      RESULTS: In non-smokers, mean arterial pressure (+8 +/- 1 mmHg, P<0.001) and
      heart rate (+13 +/- 3 beats/min, P<0.001) increased whereas effective renal
      plasma flow (ERPF) and glomerular filtration rate (GFR) decreased by 15 +/- 4%
      and 14 +/- 4% respectively; in addition, urinary cyclic GMP decreased by 51 +/-
      12% in response to nicotine administration. In smokers, mean arterial pressure
      and heart rate increased similarly; however, in contrast with non-smokers, ERPF
      and GFR remained unchanged whereas urinary cyclic GMP rose by 87 +/- 43%. Changes
      in ERPF induced by nicotine were positively correlated with changes in urinary
      cyclic GMP. CONCLUSIONS: These findings indicate that nicotine administration is
      associated with renal vasoconstriction in healthy non-smokers, possibly through
      alteration of a cyclic-GMP-dependent vasoactive mechanism. Tolerance to the renal
      effect of nicotine was observed in chronic smokers, despite the maintenance of
      the systemic response to nicotine.

PMID- 9568856
TI  - Microbiological quality of water and dialysate in all haemodialysis centres of
      Greece.
AB  - BACKGROUND: Bacterial contamination of treated water and dialysate comprises an
      important problem for patients undergoing haemodialysis. Both the progressive
      reduction of the thickness of cellulose membranes and the expanding use of high
      flux membranes probably enhance the risk of pyrogenic reactions, therefore
      increasing the need for atoxic water and non-pyrogenic dialysis fluid. METHODS:
      Samples of tap water, treated water, and effluent dialysate in all 85
      haemodialysis centres in Greece were examined for total heterotrophic bacteria
      counts employing the pour plate method, total and faecal coliforms, faecal
      streptococci and pseudomonas spp. using the membrane filter technique, and
      sulphite-reducing clostridia applying the most probable number method. Overall
      255 paired samples were tested from January to March 1997. RESULTS: For total
      heterotrophic bacteria, the overall compliance of treated water and dialysate to
      the American Association of Medical Instrumentation standards (<200 c.f.u./ml for
      water and <2000 c.f.u./ml for dialysate) was 92.6 and 63.7% respectively, whereas
      the compliance of tap water samples to our national standards (total
      heterotrophic bacteria < 10 c.f.u./ml and absence of the other indicator
      bacteria) was 80.7%. The most commonly isolated bacteria were pseudomonas spp.,
      found in 22.2% of treated water and 59.5% of dialysate samples, whereas the
      respective frequencies were 12.3 and 36.2% for total coliforms, 8.6 and 30.0% for
      faecal coliforms, 14.8 and 28.7% for faecal streptococci, and sulphite-reducing
      clostridia were isolated in 5.8% of dialysate samples only. Haemodialysis centres
      equipped with storage tanks for treated water experienced lower levels of total
      heterotrophic bacteria, but higher counts of total and faecal coliforms, faecal
      streptococci, and pseudomonas spp., although the difference was statistically
      significant only for faecal streptococci counts, (P<0.05). Sixty-seven
      haemodialysis centres were equipped with bacterial filters, but mean values of
      all the examined microorganisms were not statistically different from those of
      the other centres. Faecal streptococci counts in treated water samples were
      positively correlated with ageing of both haemodialysis centres (P<0.005) and
      purification system (P<0.05), whereas pseudomonas counts were significantly
      correlated with ageing of the purification system (P<0.05).

PMID- 9568855
TI  - High prevalence of carotid artery disease in patients with atheromatous renal
      artery stenosis.
AB  - BACKGROUND: Renovascular disease is the most frequently encountered secondary
      cause of hypertension and is one of the few potentially reversible causes of
      chronic renal failure. These patients are at increased risk of having
      cerebrovascular events following operative management for atheromatous renal
      artery stenosis. We studied the prevalence of carotid-artery disease in patients
      with atheromatous renal-artery stenosis. METHODS: A cross-sectional study was
      carried out on 38 consecutive patients with atheromatous renal-artery stenosis
      who underwent renal-artery balloon angioplasty. Extracranial carotid
      atherosclerosis was assessed using a commercially available colour Doppler
      scanner, depending on the velocity of the peak systolic waveform in the internal
      carotid artery, and the internal carotid-artery/common carotid-artery ratio.
      RESULTS: Twenty-one patients (55.3%) had normal or mild carotid-artery disease,
      10 (26.3%) had moderate, and 7 (18.4%) had severe carotid-artery disease. Nine
      patients had previously suffered a stroke (eight infarction, one haemorrhage) and
      one had multiple transient ischaemic attacks. CONCLUSIONS: Our results suggest
      that, in patients with atheromatous renal-artery disease severe enough to require
      angioplasty, 4 out of 10 appear to have moderate to severe carotid-artery
      disease. This may explain the increased prevalence of atherothrombotic
      cerebrovascular events in these patients, and also previous observations that,
      following operative management for atheromatous renal-artery stenosis, some
      patients had developed an acute or late cerebrovascular event. We suggest
      therefore that such patients should always be regarded as having generalized
      vascular disease not confined to one system, and need to be assessed for carotid
      artery disease prior to operative management for atheromatous renal-artery
      stenosis.

PMID- 9568857
TI  - Acetate-free biofiltration versus bicarbonate haemodialysis in the treatment of
      patients with diabetic nephropathy: a cross-over multicentric study.
AB  - BACKGROUND: Morbidity and mortality rates in diabetic patients on regular
      dialysis treatment (RDT) are higher than in non-diabetic-subjects on RDT.
      Moreover, diabetic patients experience an intradialitic morbidity unacceptably
      higher than in patients with other causes of terminal renal failure. The aim of
      the present investigation was to compare standard bicarbonate haemodialysis (BHD)
      with acetate-free biofiltration (AFB) in a group of 41 diabetic patients stable
      on dialysis treatment for 25 +/- 22 months. METHODS: Twenty-four type II and 17
      type I diabetic patients, all requiring insulin therapy, were included and were
      followed for 1 year in a 6-month cross-over randomized study for both methods.
      The analysis was carried out on dialysis symptoms, interdialysis symptoms, and
      nutritional status, and the multivariate analysis of variance for repeated
      measures on the same subjects in the two techniques was used. RESULTS: AFB
      significantly reduced dialytic and extradialytic symptoms (P=0.003 and 0.001
      respectively). Cardiovascular collapses decreased by 43%, and other dialysis
      symptoms showed a similar trend (-35%). The interdialysis symptoms decreased by
      28% and were accompanied by an increase in subjective wellbeing (39%) when
      patients were switched from traditional haemodialysis to AFB. Acid base control
      was better with AFB (P=0.01), both at the beginning and during the session.
      Slightly significant differences were also obtained for Kt/V (AFB 1.48 +/- 0.29
      vs BHD 1.38 +/- 0.30), while no significant difference was noted with respect to
      sodium mass balance, nutritional status, calorie-protein intake, nPCR, blood
      glucose profile, and insulin requirements. The number of hospital admissions and
      the mortality rate, which were much lower during the AFB than the BHD period,
      were not analysed statistically. CONCLUSIONS: AFB allows better control of some
      metabolic aspects, reduces intra- and extradialysis symptoms, and improves
      patient quality of life. Whether the long-term prognosis can be improved by AFB
      remains to be established with further studies.

PMID- 9568858
TI  - Peritoneal solute transport predicts survival on CAPD independently of residual
      renal function.
AB  - BACKGROUND: Loss of residual renal function has a profound effect on the survival
      of peritoneal dialysis patients. Less is known of the impact of peritoneal
      function. The purpose of this study was to investigate the influence of solute
      transport on clinical outcome in CAPD patients. METHODS: Two hundred and ten
      consecutive patients commencing CAPD since 1990 were enrolled into a single
      centre prospective longitudinal observational study of urea, protein, and
      peritoneal kinetics. On entry, and at 6-monthly intervals, estimations were made
      of weight, body mass index (BMI), plasma albumin, Kt/V, residual renal function
      (RRF), NPCR, low-molecular-weight solute transport (D/Pcreat), and peritoneal
      protein losses. All patients were censored in 1996, regardless of treatment
      modality. RESULTS: During the 6-year follow up period (median 22 months) there
      were 51 deaths, and the actuarial survival was 58% at 5 years. Urea, protein and
      peritoneal kinetics varied with time on dialysis: as anticipated there was a
      reduction in Kt/V, attributable to loss of RRF, whereas plasma albumin was stable
      for the first 2 years of treatment, but subsequently started to decline, a trend
      that became significant at 42 months. Peritoneal kinetics stabilized within the
      first 6 months of treatment and then showed a trend of increased solute transfer
      with time on treatment, which became significant by the end of the study.
      Comparing survivors with non-survivors Kt/V and RRF were similar at the start of
      treatment, but loss of RRF occurred significantly earlier in non-survivors than
      survivors (0.37 vs 0.68, P=0.02 at 6 months, 0.19 vs 0.54, P=0.01 at 12 months).
      D/Pcreat was also identical at commencement of treatment, but subsequently whilst
      survivors had stable solute transfer, non-survivors had consistently higher
      solute transfer beyond 6 months that reached increasing significance after 18
      months, (0.70 vs 0.67, P=0.05 at 18 months, 0.72 vs 0.66, P=0.03 at 24 months). A
      Cox proportional hazard model constructed for the variables age, sex, BMI,
      albumin, Kt/V and D/Pcreat at 6 months of treatment indicated that low Kt/V
      (P=0.004), high D/Pcreat (P=0.013) and age (P=0.028) were independent predictors
      of death. CONCLUSION: There is good reason to believe that high peritoneal solute
      transport is an independent marker of poor outcome in CAPD patients.

PMID- 9568859
TI  - Lipopolysaccharide-binding protein is present in effluents of patients with Gram
      negative and Gram-positive CAPD peritonitis.
AB  - BACKGROUND: Bacterial peritonitis is a frequent complication during treatment of
      end-stage renal failure by continuous ambulatory peritoneal dialysis. Local host
      defence mechanisms including the secretion of proinflammatory cytokines by
      peritoneal macrophages are of particular importance in the pathogenesis of
      infectious complications. LPS-binding protein (LBP) and soluble CD14 (sCD14) are
      serum factors known to regulate the endotoxin-induced cellular immune response.
      However, it is still unknown whether LBP and sCD14 are also present in the
      peritoneal effluent of CAPD patients. METHODS: Using specific immunoassays, we
      examined the concentration of LBP, sCD14 and the proinflammatory cytokines TNF
      alpha, IL-1beta and IL-6 in the dialysis effluents of 31 patients with CAPD
      associated peritonitis. Twenty patients without peritonitis served as controls.
      Intraperitoneal LPS concentrations were determined using the limulus amebocyte
      lysate assay. RESULTS: Bacterial lipopolysaccharide could be detected in 42% of
      the infected dialysis effluents. In comparison to controls (0.2 +/- 0.05
      microg/ml), LBP was significantly elevated in both gram-negative/LPS-positive
      (1.03 +/- 0.3 microg/ml) and gram-positive infections (0.5 +/- 0.14 microg/ml)
      (P<0.05). No significant differences were detected concerning the intraperitoneal
      sCD14 levels in the three patient groups. Levels of TNF-alpha, IL-1beta and IL-6
      were significantly increased in the effluents of patients with bacterial
      peritonitis compared to noninfected controls. Moreover the respective cytokine
      concentrations were significantly higher in the gram-negative/LPS-positive
      compared to the gram-positive bacterial infections (P<0.01). CONCLUSION: Our data
      demonstrate that LBP is significantly elevated in the dialysis effluents of
      patients with CAPD-associated peritonitis caused by both gram-negative and gram
      positive bacteria and might be used as a marker of intraperitoneal infection.
      Moreover, our findings support the concept that LBP enhances the effects of LPS
      on cytokine production by peritoneal macrophages. The function of LBP in gram
      positive infection remains to be further elucidated.

PMID- 9568860
TI  - Safety of ultrasound-guided percutaneous renal biopsy-retrospective analysis of
      1090 consecutive cases.
AB  - BACKGROUND: Ultrasound-guided renal biopsy with an automated spring-loaded biopsy
      device has become the standard method for kidney biopsy. Information on the
      success rate and safety of the routine use of this procedure from large series is
      not available. Such information is of interest for cost benefit considerations
      and for medicolegal purposes. We performed an audit of this procedure. SUBJECTS
      AND METHODS: From January 1993 to June 1997, 1090 percutaneous renal biopsies
      were performed in the renal units of Heidelberg (n = 557) and Karlsruhe (n = 533)
      using a spring-loaded biopsy device (Biopty; Radiplast AB, Uppsala, Sweden).
      After intensive local disinfection, biopsies were performed under local
      anaesthesia and direct visualization by ultrasound (Sonolayer SSH-140 A, Toshiba
      Inc., Japan). A puncturing adaptor was used (model UAGV 009 A, Toshiba, Japan).
      Of the 1090 biopsies 114 (10.4%) were performed on renal allografts and 976
      (89.6%) on orthotopic kidneys. Biopsies were performed only if patients were
      strictly normotensive (<140/90 mmHg) and had normal coagulation parameters (PT,
      PTT, factor VIII, thrombocyte count, and bleeding time). All patients had been
      advised not to take aspirin or non-steroidal antiinflammatory agents for at least
      5 days prior biopsy. We analysed (1) yield of diagnostically useful material, and
      (2) frequency of postbiopsy complications (e.g. macrohaematuria, haematoma,
      infections, and AV fistula). RESULTS: Except for one case requiring
      interventional radiology because of persisting blood loss and three cases
      requiring blood transfusions, no serious complications were seen in the 1090
      consecutive renal biopsies, e.g. death, loss of kidney, life-threatening
      haemorrhage, or persisting haemodynamically relevant AV fistulae. The frequency
      of minor haematoma with an extension >2 x 2 cm, but no significant decrease of
      haemoglobin, was 2.2% (25/1090). Self-limited mild macrohaematuria occurred in
      0.8% (9/1090). The incidence of small, haemodynamically irrelevant AV fistulae
      detected by Doppler ultrasound was 9% (48/533). Sufficient tissue for reliable
      histopathological diagnosis was obtained in almost all cases (1077/1090 = 98.8%).
      The median number of glomeruli per biopsy sample was 9 (range 1-37). CONCLUSION:
      If contraindications, especially high blood pressure and abnormal haemostasis,
      are respected, ultrasound-guided percutaneous renal biopsy with an automated
      biopsy device is safe. Skilled operators obtain satisfactory amounts of kidney
      tissue in almost all cases.

PMID- 9568861
TI  - The use of ultrasound for the placement of dialysis catheters.
AB  - BACKGROUND: The jugular vein should be preferred to the subclavian vein for the
      placement of dialysis catheters, since subclavian catheters result in a high
      incidence (up to 50%) of subclavian vein thromboses and stenoses. METHOD: We
      conducted a prospective, randomized study between July 1996 and March 1997 to
      find out whether through the use of ultrasound, the rate of unsuccessful attempts
      in puncturing the internal jugular vein could be reduced. Seventy-three internal
      jugular vein cannulations were performed on 65 patients, using the guide-wire
      technique (according to Seldinger). Two groups were formed randomly by lot: in
      the first group the position of the internal jugular vein was marked on the skin
      by the use of ultrasound (Picker CS9100, Convex 3.5 MHz) before disinfection and
      local anaesthesia took place. The puncture was performed according to this mark.
      In the second group, the internal jugular vein was cannulated with real-time
      ultrasound guidance on the monitor. Any withdrawal of the needle with a
      consecutive forward movement was judged as an unsuccessful attempt, whether or
      not a second skin puncture was performed. RESULT: Thirty-seven punctures of the
      internal jugular vein with a skin mark determined by ultrasound yielded 87
      unsuccessful attempts. Thirty-six punctures with real-time ultrasound guidance
      resulted in 10 unsuccessful attempts (P<0.01). The time from the beginning of the
      local anaesthesia to successful puncture was 4.8+/-2.2 min in the first group
      compared to 3.4+/-0.9 min in the second group (P<0.01). The cross-section of the
      internal jugular vein in the first group was 1.7+/-0.8 cm2 versus 1.5+/-0.8 cm2
      in the second group (not significant). Neither of the two methods caused any
      complications. CONCLUSION: The puncture of the internal jugular vein with real
      time ultrasound guidance resulted in significantly fewer unsuccessful attempts of
      venepuncture without requiring additional time.

PMID- 9568862
TI  - Prolonged renal dysfunction secondary to renal-artery stenosis in the elderly--it
      is never too late.

PMID- 9568863
TI  - Antineutrophil cytoplasmic autoantibodies in atheroembolic disease.

PMID- 9568864
TI  - Henoch-Schonlein purpura associated with human immunodeficiency virus infection.

PMID- 9568865
TI  - Mesangioproliferative glomerulonephritis, antiphospholipid antibodies, and
      Takayasu's arteritis--is there a link?

PMID- 9568866
TI  - Exercise-induced acute renal failure in a patient with congenital renal
      hypouricaemia.

PMID- 9568867
TI  - Recurrence of 2,8-dihydroxyadenine tubulointerstitial lesions in a kidney
      transplant recipient with a primary presentation of chronic renal failure.

PMID- 9568868
TI  - Recurrent graft pyelonephritis and pneumaturia resulting from a colovesical
      fistula secondary to silent diverticulitis.

PMID- 9568870
TI  - Interactions with ciprofloxacin and erythromycin leading to aminophylline
      toxicity.

PMID- 9568869
TI  - Drug fever induced by azathioprine in a haemodialysis patient.

PMID- 9568871
TI  - Pseudoaneurysm of the thyrocervical trunk complicating percutaneous internal
      jugular-vein catheterization for haemodialysis.

PMID- 9568872
TI  - Efficacy of continuous venovenous haemofiltration (CVVH) in the treatment of
      severe phenformin-induced lactic acidosis.

PMID- 9568873
TI  - Acute pseudorejection--intermittent dextrorotation of the uterus causing graft
      compression.

PMID- 9568874
TI  - Massive haemorrhage and rupture of renal transplant from a donor who died of
      snake bite.

PMID- 9568875
TI  - Successful resection of an infarcted lower pole in a transplanted kidney.

PMID- 9568876
TI  - Phrenic nerve palsy caused by subclavian vein catheterization.

PMID- 9568877
TI  - The dialysis patient who developed supraclavicular swelling and haemoptysis.

PMID- 9568879
TI  - 'Eye-witness'.

PMID- 9568878
TI  - Images in nephrology. 'Peanut kidney'.

PMID- 9568880
TI  - 'Bad dietary habits' and recurrent calcium oxalate nephrolithiasis.

PMID- 9568881
TI  - The description of polycystic kidney by Domenico Gusmano Galeazzi.

PMID- 9568882
TI  - Dr N. S. Korotkov: the low-pitch sounds that stand high.

PMID- 9568883
TI  - Individual kidney function in atherosclerotic renal-artery disease.

PMID- 9568884
TI  - Glomerulonephritis in sarcoidosis.

PMID- 9568885
TI  - A case of membranous glomerulonephritis associated with adenocarcinoma of
      pancreas.

PMID- 9568886
TI  - Is dialysis indicated immediately after administration of iodinated contrast
      agents in patients on haemodialysis?

PMID- 9568887
TI  - Is there a role for parathormone in the pathogenesis of colonic angiodysplasia?

PMID- 9568888
TI  - Experience with i.v. iron chondroitin-sulphate colloid in Japanese haemodialysis
      patients.

PMID- 9568889
TI  - Colchicine controversy.

PMID- 9568891
TI  - Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2 A
      resolution structure in a hexagonal crystal form.
AB  - The crystal structure of the NS3 protease of the hepatitis C virus (BK strain)
      has been determined in the space group P6(3)22 to a resolution of 2.2 A. This
      protease is bound with a 14-mer peptide representing the central region of the
      NS4A protein. There are two molecules of the NS3(1-180)-NS4A(21'-34') complex per
      asymmetric unit. Each displays a familiar chymotrypsin-like fold that includes
      two beta-barrel domains and four short alpha-helices. The catalytic triad (Ser
      139, His-57, and Asp-81) is located in the crevice between the beta-barrel
      domains. The NS4A peptide forms an almost completely enclosed peptide surface
      association with the protease. In contrast to the reported H strain complex of
      NS3 protease-NS4A peptide in a trigonal crystal form (Kim JL et al., 1996, Cell
      87:343-355), the N-terminus of the NS3 protease is well-ordered in both molecules
      in the asymmetric unit of our hexagonal crystal form. The folding of the N
      terminal region of the NS3 protease is due to the formation of a three-helix
      bundle as a result of crystal packing. When compared with the unbound structure
      (Love RA et al., 1996, Cell 87:331-342), the binding of the NS4A peptide leads to
      the ordering of the N-terminal 28 residues of the NS3 protease into a beta-strand
      and an alpha-helix and also causes local rearrangements important for a
      catalytically favorable conformation at the active site. Our analysis provides
      experimental support for the proposal that binding of an NS4A-mimicking peptide,
      which increases catalytic rates, is necessary but not sufficient for formation of
      a well-ordered, compact and, hence, highly active protease molecule.

PMID- 9568892
TI  - Thermodynamic and structural consequences of flexible loop deletion by circular
      permutation in the streptavidin-biotin system.
AB  - A circularly permuted streptavidin (CP51/46) has been designed to remove the
      flexible polypeptide loop that undergoes an open to closed conformational change
      when biotin is bound. The original termini have been joined by a tetrapeptide
      linker, and four loop residues have been removed, resulting in the creation of
      new N- and C-termini. Isothermal titration calorimetric studies show that the
      association constant has been reduced approximately six orders of magnitude below
      that of wild-type streptavidin to 10(7) M(-1). The deltaH degrees of biotin
      association for CP51/46 is reduced by 11.1 kcal/mol. Crystal structures of
      CP51/46 and its biotin complex show no significant alterations in the binding
      site upon removal of the loop. A hydrogen bond between Ser45 and Ser52 found in
      the absence of biotin is broken in the closed conformation as the side-chain
      hydroxyl of Ser45 moves to hydrogen bond to a ureido nitrogen of biotin. This is
      true in both the wild-type and CP51/46 forms of the protein, and the hydrogen
      bonding interaction might thus help nucleate closure of the loop. The reduced
      entropic cost of binding biotin to CP51/46 is consistent with the removal of this
      loop and a reduction in entropic costs associated with loop closure and
      immobilization. The reduced enthalpic contribution to the free energy of binding
      is not readily explainable in terms of the molecular structure, as the binding
      contacts are nearly entirely conserved, and only small differences in solvent
      accessible surfaces are observed relative to wild-type streptavidin.

PMID- 9568890
TI  - Molecular mechanisms for the conversion of zymogens to active proteolytic
      enzymes.
AB  - Proteolytic enzymes are synthesized as inactive precursors, or "zymogens," to
      prevent unwanted protein degradation, and to enable spatial and temporal
      regulation of proteolytic activity. Upon sorting or appropriate
      compartmentalization, zymogen conversion to the active enzyme typically involves
      limited proteolysis and removal of an "activation segment." The sizes of
      activation segments range from dipeptide units to independently folding domains
      comprising more than 100 residues. A common form of the activation segment is an
      N-terminal extension of the mature enzyme, or "prosegment," that sterically
      blocks the active site, and thereby prevents binding of substrates. In addition
      to their inhibitory role, prosegments are frequently important for the folding,
      stability, and/or intracellular sorting of the zymogen. The mechanisms of
      conversion to active enzymes are diverse in nature, ranging from enzymatic or
      nonenzymatic cofactors that trigger activation, to a simple change in pH that
      results in conversion by an autocatalytic mechanism. Recent X-ray
      crystallographic studies of zymogens and comparisons with their active
      counterparts have identified the structural changes that accompany conversion.
      This review will focus upon the structural basis for inhibition by activation
      segments, as well as the molecular events that lead to the conversion of zymogens
      to active enzymes.

PMID- 9568893
TI  - Molecular dynamics simulations of hydrophobic collapse of ubiquitin.
AB  - Nine nonnative conformations of ubiquitin, generated during two different thermal
      denaturation trajectories, were simulated under nearly native conditions (62
      degrees C). The simulations included all protein and solvent atoms explicitly,
      and simulation times ranged from 1-2.4 ns. The starting structures had alpha
      carbon root-mean-square deviations (RMSDs) from the crystal structure of 4-12 A
      and radii of gyration as high as 1.3 times that of the native state. In all but
      one case, the protein collapsed when the temperature was lowered and sampled
      conformations as compact as those reached in a control simulation beginning from
      the crystal structure. In contrast, the protein did not collapse when simulated
      in a 60% methanol:water mixture. The behavior of the protein depended on the
      starting structure: during simulation of the most native-like starting structures
      (<5 A RMSD to the crystal structure) the RMSD decreased, the number of native
      hydrogen bonds increased, and the secondary and tertiary structure increased.
      Intermediate starting structures (5-10 A RMSD) collapsed to the radius of
      gyration of the control simulation, hydrophobic residues were preferentially
      buried, and the protein acquired some native contacts. However, the protein did
      not refold. The least native starting structures (10-12 A RMSD) did not collapse
      as completely as the more native-like structures; instead, they experienced large
      fluctuations in radius of gyration and went through cycles of expansion and
      collapse, with improved burial of hydrophobic residues in successive collapsed
      states.

PMID- 9568894
TI  - Crystal structure of recombinant human tissue kallikrein at 2.0 A resolution.
AB  - Human tissue kallikrein, a trypsin-like serine protease involved in blood
      pressure regulation and inflammation processes, was expressed in a deglycosylated
      form at high levels in Pichia pastoris, purified, and crystallized. The crystal
      structure at 2.0 A resolution is described and compared with that of porcine
      kallikrein and of other trypsin-like proteases. The active and S1 sites
      (nomenclature of Schechter I, Berger A, 1967, Biochem Biophys Res Commun 27:157
      162) are similar to those of porcine kallikrein. Compared to trypsin, the S1 site
      is enlarged owing to the insertion of an additional residue, cis-Pro 219. The
      replacement Tyr 228 --> Ala further enlarges the S1 pocket. However, the
      replacement of Gly 226 in trypsin with Ser in human tissue kallikrein restricts
      accessibility of substrates and inhibitors to Asp 189 at the base of the S1
      pocket; there is a hydrogen bond between O delta1Asp189 and O gammaSer226. These
      changes in the architecture of the S1 site perturb the binding of inhibitors or
      substrates from the modes determined or inferred for trypsin. The crystal
      structure gives insight into the structural differences responsible for changes
      in specificity in human tissue kallikrein compared with other trypsin-like
      proteases, and into the structural basis for the unusual specificity of human
      tissue kallikrein in cleaving both an Arg-Ser and a Met-Lys peptide bond in its
      natural protein substrate, kininogen. A Zn+2-dependent, small-molecule
      competitive inhibitor of kallikrein (Ki = 3.3 microM) has been identified and the
      bound structure modeled to guide drug design.

PMID- 9568895
TI  - LIF receptor-gp130 interaction investigated by homology modeling: implications
      for LIF binding.
AB  - Leukemia inhibitory factor (LIF), a member of the gp130 family of helical
      cytokines, is involved in the hemopoietic and neural systems. The LIF signal
      transducing complex contains two receptor molecules, the LIF receptor (LIFR) and
      gp130. The extracellular region of the LIFR is unique in that it includes three
      membrane-proximal fibronectin type III domains and two cytokine binding domains
      (CBDs) separated by an immunoglobulin-like domain. Although some mutagenesis data
      on LIF are available, it is not yet known which regions of LIFR or gp130 bind
      LIF. Nor is it known whether LIFR contacts gp130 in a manner similar to the
      growth hormone receptor dimer and, if so, through which of its CBDs. To attempt
      to elucidate these matters and to investigate the receptor complex, models of the
      CBDs of LIFR and the CBD of gp130 were constructed. Analyses of the electrostatic
      isopotential surfaces of the CBD models suggest that gp130 and the membrane
      proximal CBD of LIFR hetero-dimerize and bind LIF through contacts similar to
      those seen in the growth hormone receptor dimer. This work further demonstrates
      the utility of electrostatic analyses of homology models and suggests a strategy
      for biochemical investigations of the LIF-receptor complex.

PMID- 9568896
TI  - Heterogeneity of packing: structural approach.
AB  - Analysis of the heterogeneity of packing in proteins showed that different groups
      of the protein preferentially contribute to low- or high-density regions.
      Statistical distribution reveals the two preferable values for packing density in
      the form of two peaks. One peak occurs in the range of densities 0.55-0.65, the
      other occurs in the range 0.75-0.8. The high-density peak is originated primarily
      by high packing inside the hydrogen bonded backbone and to some extent by side
      chains. Polar/charged and apolar side chains both contribute to the low-density
      peak. The average packing density values of individual atomic groups
      significantly vary for backbone atoms as well as for side chain atoms. The
      carbonyl oxygen atoms of protein backbone and the end groups of side chains show
      lower packing density than the rest of the protein. The side-chain atomic groups
      of a secondary structure element when packed against the neighboring secondary
      structure element form stronger contacts with the side chains of this element
      than with its backbone. Analysis of the low-density regions around each buried
      peptide group was done for the set of proteins with different types of packing,
      including alpha-alpha, alpha-beta, and beta-beta packing. It was shown that
      cavities are regularly situated in the groove of secondary structure element
      packed against neighboring elements for all types of packing. Low density in the
      regions surrounding the peptide groups and the end groups of side chains can be
      explained by their positioning next to a cavity formed upon the association of
      secondary structure elements. The model proposed can be applied to the analysis
      of protein internal motions, mechanisms of cellular signal transduction,
      diffusion through protein matrix, and other events.

PMID- 9568897
TI  - The BPI/LBP family of proteins: a structural analysis of conserved regions.
AB  - Two related mammalian proteins, bactericidal/permeability-increasing protein
      (BPI) and lipopolysaccharide-binding protein (LBP), share high-affinity binding
      to lipopolysaccharide (LPS), a glycolipid found in the outer membrane of gram
      negative bacteria. The recently determined crystal structure of human BPI permits
      a structure/function analysis, presented here, of the conserved regions of these
      two proteins sequences. In the seven known sequences of BPI and LBP, 102 residues
      are completely conserved and may be classified in terms of location, side-chain
      chemistry, and interactions with other residues. We find that the most highly
      conserved regions lie at the interfaces between the tertiary structural elements
      that help create two apolar lipid-binding pockets. Most of the conserved polar
      and charged residues appear to be involved in inter-residue interactions such as
      H-bonding. However, in both BPI and LBP a subset of conserved residues with
      positive charge (lysines 42, 48, 92, 95, and 99 of BPI) have no apparent
      structural role. These residues cluster at the tip of the NH2-terminal domain,
      and several coincide with residues known to affect LPS binding; thus, it seems
      likely that these residues make electrostatic interactions with negatively
      charged groups of LPS. Overall differences in charge and electrostatic potential
      between BPI and LBP suggest that BPI's bactericidal activity is related to the
      high positive charge of its NH2-terminal domain. A model of human LBP derived
      from the BPI structure provides a rational basis for future experiments, such as
      site-directed mutagenesis and inhibitor design.

PMID- 9568898
TI  - The structure of a glycogen phosphorylase glucopyranose spirohydantoin complex at
      1.8 A resolution and 100 K: the role of the water structure and its contribution
      to binding.
AB  - A glucopyranose spirohydantoin (a pyranose analogue of the potent herbicide,
      hydantocidin) has been identified as the highest affinity glucose analogue
      inhibitor of glycogen phosphorylase b (GPb). In order to elucidate the structural
      features that contribute to the binding, the structures of GPb in the native T
      state conformation and in complex with glucopyranose spirohydantoin have been
      determined at 100 K to 2.0 A and 1.8 A resolution, respectively, and refined to
      crystallographic R values of 0.197 (R[free] 0.248) and 0.182 (R[free] 0.229),
      respectively. The low temperature structure of GPb is almost identical to that of
      the previously determined room temperature structure, apart from a decrease in
      overall atomic temperature factors ((B) room temperature GPb = 34.9 A2; (B) 100 K
      GPb = 23.4 A2). The glucopyranose spirohydantoin inhibitor (Ki = 3.0 microM)
      binds at the catalytic site and induces small changes in two key regions of the
      protein: the 280s loop (residues 281-286) that results in a decrease in mobility
      of this region, and the 380s loop (residues 377-385) that undergoes more
      significant shifts in order to optimize contact to the ligand. The hydantoin
      group, that is responsible for increasing the affinity of the glucose compound by
      a factor of 10(3), makes only one hydrogen bond to the protein, from one of its
      NH groups to the main chain oxygen of His377. The other polar groups of the
      hydantoin group form hydrogen bonds to five water molecules. These waters are
      involved in extensive networks of hydrogen bonds and appear to be an integral
      part of the protein structure. Analysis of the water structure at the catalytic
      site of the native enzyme, shows that five waters are displaced by ligand binding
      and that there is a significant decrease in mobility of the remaining waters on
      formation of the GPb-hydantoin complex. The ability of the inhibitor to exploit
      existing waters, to displace waters and to recruit new waters appears to be
      important for the high affinity of the inhibitor.

PMID- 9568899
TI  - NMR determination of the global structure of the 113Cd derivative of
      desulforedoxin: investigation of the hydrogen bonding pattern at the metal
      center.
AB  - Desulforedoxin (Dx) is a simple homodimeric protein isolated from Desulfovibrio
      gigas (Dg) containing a distorted rubredoxin-like center with one iron
      coordinated by four cysteinyl residues (7.9 kDa with 36 amino acids per monomer).
      In order to probe the geometry and the H-bonding at the active site of Dx, the
      protein was reconstituted with 113Cd and the solution structure determined using
      2D NMR methods. The structure of this derivative was initially compared with the
      NMR solution structure of the Zn form (Goodfellow BJ et al., 1996, J Biol Inorg
      Chem 1:341-353). Backbone amide protons for G4, D5, G13, L11 NH, and the Q14 NH
      side-chain protons, H-bonded in the X-ray structure, were readily exchanged with
      solvent. Chemical shift differences observed for amide protons near the metal
      center confirm the H-bonding pattern seen in the X-ray model (Archer M et al.,
      1995, J Mol Biol 251:690-702) and also suggest that H-bond lengths may vary
      between the Fe, Zn, and 113Cd forms. The H-bonding pattern was further probed
      using a heteronuclear spin echo difference (HSED) experiment; the results confirm
      the presence of NH-S H-bonds inferred from D2O exchange data and observed in the
      NMR family of structures. The presence of "H-bond mediated" coupling in Dx
      indicates that the NH-S H-bonds at the metal center have significant covalent
      character. The HSED experiment also identified an intermonomer "through space"
      coupling for one of the L26 methyl groups, indicating its proximity to the 113Cd
      center in the opposing monomer. This is the first example of an intermonomer
      "through space" coupling. Initial structure calculations produced subsets of NMR
      families with the S of C28 pointing away from or toward the L26 methyl: only the
      subset with the C28 sulfur pointing toward the L26 methyl could result in a
      "through space" coupling. The HSED result was therefore included in the structure
      calculations. Comparison of the Fe, Zn, and 113Cd forms of Dx suggests that the
      geometry of the metal center and the global fold of the protein does not vary to
      any great extent, although the H-bond network varies slightly when Cd is
      introduced. The similarity between the H-bonding pattern seen at the metal center
      in Dx, Rd (including H-bonded and through space-mediated coupling), and many zinc
      finger proteins suggests that these H-bonds are structurally vital for
      stabilization of the metal centers in these proteins.

PMID- 9568901
TI  - Mapping of the interleukin-10/interleukin-10 receptor combining site.
AB  - The discontinuous interleukin-10(IL-10)/interleukin-10 receptor (IL-10R)
      combining site was mapped using sets of overlapping peptides derived from both
      binding partners bound to continuous cellulose membranes. Low affinity binding of
      single regions of the discontinuous contact sites on IL-10 and IL-10R could be
      identified due to (1) high peptide density on the membrane support, (2)
      incubation with high protein concentrations, (3) indirect immunodetection of the
      ligates after electrotransfer onto polyvinylene difluoride membranes, and (4) use
      of highly overlapping peptide scans of different length (6-mers and 15-mers). The
      single binding regions identified for each protein species are separated in the
      protein sequences, but form continuous areas on the surface of IL-10 (X-ray
      structure) and IL-10R (computer model). Furthermore, four epitopes of
      neutralizing anti-IL-10 and anti-IL-10R antibodies were mapped and overlap with
      these binding regions. Soluble peptides (15- to 19-mers) each spanning one of the
      three identified IL-10-derived receptor binding regions displayed no significant
      affinity to IL-10R as expected, whereas a peptide (35-mer) comprising two of
      these regions had considerably higher binding activity. The data are consistent
      with a previously published computer model of the IL-10/IL-10R complex. This
      approach should be generally applicable for the mapping of non-linear protein
      protein contact sites.

PMID- 9568900
TI  - Flexible ligand docking using conformational ensembles.
AB  - Molecular docking algorithms suggest possible structures for molecular complexes.
      They are used to model biological function and to discover potential ligands. A
      present challenge for docking algorithms is the treatment of molecular
      flexibility. Here, the rigid body program, DOCK, is modified to allow it to
      rapidly fit multiple conformations of ligands. Conformations of a given molecule
      are pre-calculated in the same frame of reference, so that each conformer shares
      a common rigid fragment with all other conformations. The ligand conformers are
      then docked together, as an ensemble, into a receptor binding site. This takes
      advantage of the redundancy present in differing conformers of the same molecule.
      The algorithm was tested using three organic ligand protein systems and two
      protein-protein systems. Both the bound and unbound conformations of the
      receptors were used. The ligand ensemble method found conformations that
      resembled those determined in X-ray crystal structures (RMS values typically less
      than 1.5 A). To test the method's usefulness for inhibitor discovery, multi
      compound and multi-conformer databases were screened for compounds known to bind
      to dihydrofolate reductase and compounds known to bind to thymidylate synthase.
      In both cases, known inhibitors and substrates were identified in conformations
      resembling those observed experimentally. The ligand ensemble method was 100-fold
      faster than docking a single conformation at a time and was able to screen a
      database of over 34 million conformations from 117,000 molecules in one to four
      CPU days on a workstation.

PMID- 9568902
TI  - A differential scanning calorimetric study of the thermal unfolding of apo- and
      holo-cytochrome b562.
AB  - Cytochrome b562 is a four-helix-bundle protein containing a non-covalently bound
      b-type heme prosthetic group. In the absence of heme, cytochrome b562 remains
      highly structured under native conditions. Here we report thermodynamic data for
      the thermal denaturation of the holo- and apoproteins as determined by
      differential scanning calorimetry. Thermal denaturation of holocytochrome b562 is
      a highly reversible process, and unexpectedly does not involve dissociation of
      the heme prosthetic group. Thermal denaturation of the corresponding apoprotein,
      with the heme group chemically removed, remains a cooperative, reversible
      process. Apocytochrome b562 is substantially destabilized relative to the
      holoprotein: the t1/2 is more than ten degrees lower, and enthalpy and heat
      capacity changes are about one-half of the holoprotein values. However, the
      energetic parameters of apocytochrome b562 denaturation are within the range of
      observed values for small proteins.

PMID- 9568903
TI  - A monomeric mutant of Clostridium symbiosum glutamate dehydrogenase: comparison
      with a structured monomeric intermediate obtained during refolding.
AB  - The refolding of Clostridium symbiosum glutamate dehydrogenase (GDH) involves the
      formation of an inactive structured monomeric intermediate prior to its
      concentration-dependent association. The structured monomer obtained after
      removal of guanidinium chloride was stable and competent for reconstitution into
      active hexamers. Site-directed mutagenesis of C. symbiosum gdh gene was performed
      to replace the residues Arg-61 and Phe-187 which are involved in subunit-subunit
      interactions, as determined by three-dimensional structure analysis. Heterologous
      over-expression in Escherichia coli of the double mutant (R61E/F187D) led to the
      production of a soluble protein with a molecular mass consistent with the
      monomeric form of clostridial GDH. This protein is catalytically inactive but
      cross-reacts with an anti-wild-type GDH antibody preparation. The double mutant
      R61E/F187D does not assemble into hexamers. The physical properties and the
      stability toward guanidinium chloride and urea of R61E/F187D were studied and
      compared to those of the structured monomeric intermediate.

PMID- 9568904
TI  - Conformational diversity of acid-denatured cytochrome c studied by a matrix
      analysis of far-UV CD spectra.
AB  - The singular value decomposition (SVD) analysis was applied to a large set of far
      ultraviolet circular dichroism (far-UV CD) spectra (100-400 spectra) of horse
      heart cytochrome c (cyt c). The spectra were collected at pH 1.7-5.0 in
      (NH4)2SO4, sorbitol and 2,2,2-trifluoroethanol (TFE) solutions. The present
      purpose is to develop a rigorous matrix method applied to far-UV CD spectra to
      resolve in details conformational properties of proteins in the non-native (or
      denatured) regions. The analysis established that three basis spectral components
      are contained in a data set of difference spectra (referred to the spectrum of
      the native state) used here. By a further matrix transformation, any observed
      spectrum could be decomposed into fractions of the native (N), the molten-globule
      (MG), the highly denatured (D), and the alcohol-induced helical (H) spectral
      forms. This method could determine fractional transition curves of each conformer
      as a function of solution conditions, which gave the results consistent with
      denaturation curves of cyt c monitored by other spectroscopic methods. The
      results in sorbitol solutions, for example, suggested that the preferential
      hydration effect of the co-solvent stabilizes the MG conformer of cyt c. This
      report has found that the systematic SVD analysis of the far-UV CD spectra is a
      powerful tool for the conformational analysis of the non-native species of a
      protein when it is suitably supplemented with other experimental methods.

PMID- 9568905
TI  - Solution structure and dynamics of a designed monomeric variant of the lambda Cro
      repressor.
AB  - The solution structure of a monomeric variant of the lambda Cro repressor has
      been determined by multidimensional NMR. Cro K56[DGEVK] differs from wild-type
      Cro by the insertion of five amino acids at the center of the dimer interface. 1H
      and 15N resonances for 70 of the 71 residues have been assigned. Thirty-two
      structures were calculated by hybrid distance geometry/simulated annealing
      methods using 463 NOE-distance restraints, 26 hydrogen-bond, and 39 dihedral
      angle restraints. The root-mean-square deviation (RMSD) from the average
      structure for atoms in residues 3-60 is 1.03 +/- 0.44 A for the peptide backbone
      and 1.6 +/- 0.73 A for all nonhydrogen atoms. The overall structure conforms very
      well to the original design. Although the five inserted residues form a beta
      hairpin as expected, this engineered turn as well as other turns in the structure
      are not well defined by the NMR data. Dynamics studies of backbone amides reveal
      T1/T2 ratios of residues in the alpha2-alpha3, beta2-beta3, and engineered turn
      that are reflective of chemical exchange or internal motion. The solution
      structure and dynamics are discussed in light of the conformational variation
      that has been observed in other Cro structures, and the importance of flexibility
      in DNA recognition.

PMID- 9568907
TI  - Characterization of the recombinant extracellular domain of the neurotrophin
      receptor TrkA and its interaction with nerve growth factor (NGF).
AB  - Nerve growth factor (NGF) is the prototype of a family of neurotrophins that
      support important neuronal programs such as differentiation and survival of a
      subset of sympathetic, sensory, and brain neurons. NGF binds to two classes of
      cell surface receptors: p75LANR and p140TrkA. NGF binding to p140TrkA initiates
      the neuronal signaling pathway through activation of the tyrosine kinase
      activity, which subsequently results in a rapid signal transduction through a
      phosphorylation cascade. To examine this crucial signaling step in more detail,
      the TrkA extracellular domain polypeptide (TrkA-RED) was overexpressed in Sf21
      insect cells and purified to homogeneity. The recombinant TrkA-RED is a 70 kDa
      acidic glycoprotein with a pI of 5.1, and mimics the intact TrkA receptor for NGF
      binding with a dissociation constant, Kd, of 2.9 nM. Thus, the recombinant TrkA
      RED is functionally competent and can be used to elucidate the interaction of NGF
      and TrkA receptor. Circular dichroism difference spectra indicated that, upon
      association of NGF with TrkA-RED, a minor conformational change occurred to form
      a complex with decreased ordered secondary structure. Interaction between NGF and
      TrkA-RED was also demonstrated by size exclusion chromatography, light
      scattering, and chemical crosslinking with evidence for formation of a higher
      molecular weight complex consistent with a (TrkA-RED)2-(NGF dimer) complex.
      Association and dissociation rates of 5.6 x 10(5) M(-1) s(-1) and 1.6 x 10(-3) s(
      1), respectively, were determined by biosensor technology. Thus, initiation of
      signaling may stem from NGF-induced receptor dimerization concomitant with a
      small conformational change.

PMID- 9568906
TI  - Mutagenesis of histidine 26 demonstrates the importance of loop-loop and loop
      protein interactions for the function of iso-1-cytochrome c.
AB  - In yeast iso-1-cytochrome c, the side chain of histidine 26 (His26) attaches
      omega loop A to the main body of the protein by forming a hydrogen bond to the
      backbone atom carbonyl of glutamic acid 44. The His26 side chain also forms a
      stabilizing intra-loop interaction through a hydrogen bond to the backbone amide
      of asparagine 31. To investigate the importance of loop-protein attachment and
      intra-loop interactions to the structure and function of this protein, a series
      of site-directed and random-directed mutations were produced at His26. Yeast
      strains expressing these variant proteins were analyzed for their ability to grow
      on non-fermentable carbon sources and for their intracellular production of
      cytochrome c. While the data show that mutations at His26 lead to slightly
      decreased intracellular amounts of cytochrome c, the level of cytochrome c
      function is decreased more. The data suggest that cytochrome c reductase binding
      is affected more than cytochrome c oxidase or lactate dehydrogenase binding. We
      propose that mutations at this residue increase loop mobility, which, in turn,
      decreases the protein's ability to bind redox partners.

PMID- 9568908
TI  - Trapping of intermediates during the refolding of recombinant human epidermal
      growth factor (hEGF) by cyanylation, and subsequent structural elucidation by
      mass spectrometry.
AB  - Human epidermal growth factor (hEGF) contains 53 amino acids and three disulfide
      bonds. The unfolded, reduced hEGF is allowed to refold under mildly alkaline
      conditions. The folding is quenched at different time points by adjusting the pH
      to 3.0 with an acetic acid solution of 1-cyano-4-dimethylamino-pyridinium (CDAP)
      which traps folding intermediates via cyanylation of free sulfhydryl groups. The
      mixture of cyanylated intermediates is separated by reversed-phase HPLC; the
      fractions collected are identified by mass spectrometry. The disulfide structures
      of the intermediates are then determined by specific chemical cleavage and mass
      mapping by MALDI-MS, a novel approach developed in our laboratory. The procedure
      of quenching and trapping of disulfide intermediates in acidic solution minimizes
      sulfhydryl-disulfide exchange, and therefore provides a good measure of folding
      kinetics and preservation of intermediate species. Our cyanylation methodology
      for disulfide mapping is simpler, faster, and more sensitive than the more
      conventional approach. Among 18 folding intermediates isolated and identified at
      different time points, disulfide structures of seven well-populated
      intermediates, including two non-native isomers with scrambled disulfide
      structures, one 2-disulfide intermediate, and four 1-disulfide intermediates,
      have been characterized; most of them possess non-native disulfide structures.

PMID- 9568909
TI  - Genome-wide analysis of integral membrane proteins from eubacterial, archaean,
      and eukaryotic organisms.
AB  - We have carried out detailed statistical analyses of integral membrane proteins
      of the helix-bundle class from eubacterial, archaean, and eukaryotic organisms
      for which genome-wide sequence data are available. Twenty to 30% of all ORFs are
      predicted to encode membrane proteins, with the larger genomes containing a
      higher fraction than the smaller ones. Although there is a general tendency that
      proteins with a smaller number of transmembrane segments are more prevalent than
      those with many, uni-cellular organisms appear to prefer proteins with 6 and 12
      transmembrane segments, whereas Caenorhabditis elegans and Homo sapiens have a
      slight preference for proteins with seven transmembrane segments. In all
      organisms, there is a tendency that membrane proteins either have many
      transmembrane segments with short connecting loops or few transmembrane segments
      with large extra-membraneous domains. Membrane proteins from all organisms
      studied, except possibly the archaeon Methanococcus jannaschii, follow the so
      called "positive-inside" rule; i.e., they tend to have a higher frequency of
      positively charged residues in cytoplasmic than in extra-cytoplasmic segments.

PMID- 9568910
TI  - Complete localization of disulfide bonds in GM2 activator protein.
AB  - Lysosomal degradation of ganglioside GM2 by hexosaminidase A requires the
      presence of a small, non-enzymatic cofactor, the GM2-activator protein (GM2AP).
      Lack of functional protein leads to the AB variant of GM2-gangliosidosis, a fatal
      lysosomal storage disease. Although its possible mode of action and functional
      domains have been discussed frequently in the past, no structural information
      about GM2AP is available so far. Here, we determine the complete disulfide bond
      pattern of the protein. Two of the four disulfide bonds present in the protein
      were open to classical determination by enzymatic cleavage and mass spectrometry.
      The direct localization of the remaining two bonds was impeded by the close
      vicinity of cysteines 136 and 138. We determined the arrangement of these
      disulfide bonds by MALDI-PSD analysis of disulfide linked peptides and by partial
      reduction, cyanylation and fragmentation in basic solution, as described recently
      (Wu F, Watson JT, 1997, Protein Sci 6:391-398).

PMID- 9568911
TI  - A cognate tRNA specific conformational change in glutaminyl-tRNA synthetase and
      its implication for specificity.
AB  - Conformational changes that occur upon substrate binding are known to play
      crucial roles in the recognition and specific aminoacylation of cognate tRNA by
      glutaminyl-tRNA synthetase. In a previous study we had shown that glutaminyl-tRNA
      synthetase labeled selectively in a nonessential sulfhydryl residue by an
      environment sensitive probe, acrylodan, monitors many of the conformational
      changes that occur upon substrate binding. In this article we have shown that the
      conformational change that occurs upon tRNA(Gln) binding to glnRS/ATP complex is
      absent in a noncognate tRNA tRNA(Glu)-glnRS/ATP complex. CD spectroscopy
      indicates that this cognate tRNA(Gln)-induced conformational change may involve
      only a small change in secondary structure. The Van't Hoff plot of cognate and
      noncognate tRNA binding in the presence of ATP is similar, suggesting similar
      modes of interaction. It was concluded that the cognate tRNA induces a local
      conformational change in the synthetase that may be one of the critical elements
      that causes enhanced aminoacylation of the cognate tRNA over the noncognate ones.

PMID- 9568912
TI  - The dimerization motif of the glycophorin A transmembrane segment in membranes:
      importance of glycine residues.
AB  - The glycophorin A transmembrane segment homo-dimerizes to a right-handed pair of
      alpha-helices. Here, we identified the amino acid motif mediating this
      interaction within a natural membrane environment. Critical residues were grafted
      onto two different hydrophobic host sequences in a stepwise manner and self
      assembly of the hybrid sequences was determined with the ToxR transcription
      activator system. Our results show that the motif LIxxGxxxGxxxT elicits a level
      of self-association equivalent to that of the original glycophorin A
      transmembrane segment. This motif is very similar to the one previously
      established in detergent solution. Interestingly, the central GxxxG motif by
      itself already induced strong self-assembly of host sequences and the three
      residue spacing between both glycines proved to be optimal for the interaction.
      The GxxxG element thus appears to be the most crucial part of the interaction
      motif.

PMID- 9568913
TI  - Crystallization and preliminary X-ray analysis of a 1:1 complex between a
      designed monomeric interferon-gamma and its soluble receptor.
AB  - A variant of human interferon-gamma (IFN-gamma) has been created in which the two
      chains of the homodimeric cytokine were linked N- to C-terminus by an eight
      residue polypeptide linker. The sequence of this linker was derived from a loop
      in bira bifunctional protein, and was determined from a structural database
      search. This "single-chain" variant was used to create an IFN-gamma molecule that
      binds only a single copy of the alpha-chain receptor, rather than the 2 alpha
      chain receptor: 1 IFN-gamma binding stoichiometry observed for the native
      hormone. Crystals have been grown of a 1:1 complex between this single-chain
      molecule and the extracellular domain of its alpha-chain receptor. These crystals
      diffract beyond 2.0 A, significantly better than the 2.9 A observed for the
      native 2:1 complex. Density calculations suggest these crystals contain two
      complexes in the asymmetric unit; a self-rotation function confirms this
      conclusion.

PMID- 9568914
TI  - Recollections of a DNA enzymologist.

PMID- 9568915
TI  - The clinical course of Canavan disease.
AB  - Canavan, an autosomal-recessive neurodegenerative disease, is caused by a
      deficiency of aspartoacylase. Most children are reported to have the infantile
      form, becoming symptomatic between 3 and 6 months of age, after an unremarkable
      prenatal and perinatal course. Congenital and juvenile onset forms, although
      uncommon, do occur. We collected clinical information from the parents of 60
      children diagnosed with Canavan disease and reviewed the literature. We conclude
      that Canavan disease is prenatal in onset with variability in progression. The
      variable clinical course cannot be explained by genetic heterogeneity but
      probably depends on environmental factors and/or modifying genes.

PMID- 9568916
TI  - Risk factors analysis for early fatality in children with acute bacterial
      meningitis.
AB  - To identify the cause of early fatality and to delineate the clinical findings on
      admission associated with this early fatality, a retrospective study of 101
      children with bacterial meningitis was performed in southern Taiwan. Risk factors
      for early fatality are compared between patients with and without acute death in
      the first 3 days after admission. The overall patient fatality is 27%. Eighty
      five percent of them (23 patients) occur at an average of 16.5 hours after
      admission despite proper antibiotic treatment. The causes of early death are
      predominantly hemodynamic in 14 patients (61%) and predominantly neurologic in
      nine (39%). Analysis of clinical parameters available on admission indicated a
      significant risk of early death in patients who have tachycardia, tachypnea,
      hypothermia, poor skin perfusion, metabolic acidosis, leukopenia,
      thrombocytopenia, low cerebrospinal fluid leukocyte count, and high cerebrospinal
      fluid lactate level. Multivariate analysis demonstrates that metabolic acidosis,
      poor skin perfusion, and low cerebrospinal fluid leukocyte count are
      independently and significantly associated with early fatality. In conclusion,
      two thirds of early fatalities in children with bacterial meningitis are the
      result of septic shock. Close surveillance for signs of septic shock, as well as
      of brain herniation should be continued, especially within 3 days after
      antibiotic treatment.

PMID- 9568917
TI  - Risk of recurrence and outcome after the first febrile seizure.
AB  - After their first febrile seizure, 180 children were prospectively monitored to
      provide data for a quantitative and qualitative analysis of the factors affecting
      the risk of recurrence of febrile seizures and to evaluate the influence of
      recurrences on the outcome. Of these children, 153 had subsequent febrile
      episodes and were included in the risk-factor analysis. The outcome was evaluated
      after a 2-year follow-up in 156 children. Each febrile episode increased the risk
      of recurrence by 18%. Each degree of increase in temperature (Celsius) during
      subsequent infections almost doubled the risk of recurrence. Age, sex, the type
      of initial seizure, the temperature during the initial seizure, or a family
      history of febrile seizures or epilepsy did not influence the recurrence rate
      significantly. The results indicate that procedures that minimize the probability
      of febrile infections would decrease the risk of recurrences of febrile seizures.

PMID- 9568918
TI  - Normal developmental changes in carotid artery diameter measured by echo
      tracking.
AB  - We examined the developmental changes in carotid arterial diameter and its change
      with pulsatile pressure in infants and children using the phase-locked echo
      tracking method. The mean, maximum systolic, and minimum diastolic carotid
      arterial diameter and pulsating diameter changes were measured in 95 healthy
      children aged 1 month to 13 years. The mean, maximum, and minimum carotid
      arterial diameter increase significantly and exponentially with age, body weight,
      height, and body surface area, and the correlation coefficient was highest with
      body surface area. The change in carotid arterial diameter with pulse pressure
      increased gradually until 2 to 3 years of age. Our results suggest that the
      maturational changes in carotid diameter and the dynamic changes in the diameter
      reflect changes in the carotid-cerebral circulatory system. The noninvasive
      measurement of the carotid diameter and pulsating diameter changes by a phase
      locked echo-tracking method is useful for examining carotid-cerebral circulatory
      disorders.

PMID- 9568920
TI  - Overstimulation of nerve growth factors in postinfectious and autoimmune
      diseases.
AB  - Nerve growth factor (NGF) in cerebrospinal fluid was measured by ELISA in ten
      children with postinfectious diseases and in five children with diseases
      suggested to be of autoimmune etiology. Three groups of patients were studied:
      (1) those with moderately elevated concentrations (50.67 +/- 17.02 pg/mL, mean
      and SEM), (2) those with high concentrations (mean 424.25 +/- 125.41 pg/mL, mean
      and SEM), and (3) those with enormously high concentrations (mean 2,745 +/-
      1,819.46 pg/mL, mean and SEM). We suggest that CSF-NGF could be used as an
      immunologic marker of an ongoing CNS process. Uncontrolled signaling of NGF
      receptors may lead to long-term inflammatory and autoimmune responses, which in
      turn can lead to disease.

PMID- 9568919
TI  - Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1.
AB  - Neurofibromin, the protein product of the neurofibromatosis type 1 (NF-1) gene,
      has important roles in tumor suppression or normal embryogenesis. Cerebellar
      leptomeningeal astroglial heterotopia (LAH) is a proliferation of heterotopic
      astroglial cells and fibers in the cerebellar leptomeninges, which is
      characteristically demonstrated in the NF-1 patients. In this study,
      neurofibromin expression was investigated in NF-1 and non-NF-1 human tissues,
      especially in the cerebellum of NF-1 patients. Neurofibromin was found by
      immunoblotting in the CNS but not in the heart, liver, and kidney.
      Immunohistochemistry in the normal areas of the brains with NF-1 demonstrated
      neurofibromin immunoreactivity as did the brains of unaffected controls.
      Cerebellar LAH showed no neurofibromin immunoreactivity. The results of this
      study suggest that neurofibromin expression remains unchanged in the
      nonproliferated region of the CNS of the NF-1 patient but changes occur in the
      abnormally proliferated region, resulting in cerebellar LAH. Loss of
      neurofibromin may result in the excessive migration and growth of astrocytes in
      the early fetal period.

PMID- 9568921
TI  - Effects of prenatal substance exposure: altered maturation of visual evoked
      potentials.
AB  - We investigated the effects of prenatal substance use on visual evoked potentials
      (VEPs). Seventy-four children were tested at birth and 1 month of age with
      binocular flash VEPs and at 4, 8, and 18 months of age with binocular pattern
      VEPs. Regressions were run by trimester to assess the independent effects of
      substance exposure. Variables included in the regression model were alcohol,
      marijuana, tobacco, other drug use for each trimester, maternal age, education,
      income, race, marital status, infant sex, birthweight, and Dubowitz score.
      Changes in specific components of the binocular VEP were both substance- and
      trimester-specific. First trimester alcohol use was associated with prolonged P1
      wave latencies at 1 month of age. Prolonged P1 wave latencies at birth and 18
      months were associated with tobacco use during each of the three trimesters, at 1
      and 18 months with third trimester marijuana use, and at 1 and 18 months with
      first trimester other illicit drug use. Although these women were moderate
      substance users during pregnancy, their offspring exhibited maturational changes
      in components of the VEP in the absence of neonatal behavioral disturbances.

PMID- 9568922
TI  - Methylphenidate effects on EEG, behavior, and performance in boys with ADHD.
AB  - The psychophysiologic and behavioral effects of methylphenidate were assessed in
      boys with attention deficit hyperactivity disorder between the ages of 9 and 11
      years. The effects of methylphenidate on the EEG during baseline and cognitive
      tasks were evaluated using spectral analysis. Both subjective (rating scales) and
      objective (continuous performance) measures were administered and analyzed in
      conjunction with the electrophysiologic data. Although methylphenidate induced
      regional changes in the EEG under certain task-specific conditions, it had no
      global effects. Behavioral and performance measures improved with
      methylphenidate.

PMID- 9568923
TI  - Acute hepatic failure in a child treated with lamotrigine.
AB  - An 8-year-old boy with a known seizure disorder that was being treated with
      lamotrigine developed acute hepatic failure. The patient, who had been well
      previously, presented with jaundice, elevated liver enzymes, and a coagulopathy.
      After discontinuation of lamotrigine and aggressive resuscitation, the patient
      made an uneventful recovery. We believe that the hepatic failure in our patient
      was secondary to the use of lamotrigine. We recommend careful monitoring of liver
      function when lamotrigine is administered.

PMID- 9568924
TI  - 3-Hydroxyisobutyric aciduria in two brothers.
AB  - Two Japanese brothers with 3-hydroxyisobutyric aciduria (3HiB-uria) are studied.
      The elder brother died of a ketoacidotic episode at the age of 4 years; the
      younger brother also manifested repeated episodes of ketoacidosis after 1 year of
      age. He is diagnosed as having 3HiB-uria by gas chromatography/mass spectometry
      analysis, using the unique fragment ions of 3HiB. Magnetic resonance imaging
      reveals focal white matter abnormalities. Protein restriction is effective for
      preventing the ketoacidotic episodes, although carnitine therapy seems less
      effective.

PMID- 9568925
TI  - Acute childhood hemiplegia associated with chickenpox.
AB  - Although primary varicella-associated central nervous system complications and
      herpes zoster ophthalmicus with delayed hemiplegia are well known, and chickenpox
      is a common infection, cerebral vasculopathy associated with chickenpox has only
      been described recently. We report the case of an 18-month-old girl who developed
      a right hemiplegia 10 days after the onset of a primary varicella infection. She
      has the shortest latent interval in the literature. Cranial computed tomography
      and magnetic resonance imaging suggest an infarction involving the left putamen
      and internal capsule. Magnetic resonance angiography is normal. Possible causes
      of acute infantile hemiplegia are excluded. Neurologic signs gradually improve
      without any specific treatment. A review of the literature is also presented.

PMID- 9568926
TI  - Stroke in a neonate heterozygous for factor V Leiden.
AB  - Activated protein C resistance is the most common hereditary coagulation
      abnormality and is caused by the factor V Leiden mutation. A newborn who
      developed seizures within hours after delivery and was found to have a
      bihemispheric stroke is described. This patient, determined to be heterozygous
      for factor V Leiden, is the first reported case of neonatal stroke associated
      with this common mutation.

PMID- 9568927
TI  - Clinical and electroencephalographic findings in juvenile type DRPLA.
AB  - We present five different types of dentatorubral-pallidoluysian atrophy in one
      Japanese family. Two siblings and their paternal uncle manifested the juvenile
      type dentatorubral-pallidoluysian atrophy, the siblings' father had the late
      adult type, and another paternal uncle had the early-adult type. Gene analysis
      confirmed the diagnosis for the proband and her sibling. By following the
      clinical courses and electroencephalographic changes, we found that the types of
      epileptic seizures and the electroencephalograms of the juvenile dentatorubral
      pallidoluysian atrophy patients changed as the illness progressed. The siblings
      exhibited different levels of clinical severity despite the similar
      deoxyribonucleic acid expansion detected in their lymphocytes.

PMID- 9568928
TI  - MRI diagnosis of NF-1 in children without cafe-au-lait skin lesions.
AB  - Three of ten children with optic gliomas satisfy the 1987 National Institutes of
      Health consensus criteria for neurofibromatosis type 1 (NF-1). The diagnosis in
      these cases is based on the presence of cafe-au-lait skin lesions in addition to
      the optic glioma. Two children without skin lesions have typical findings on
      magnetic resonance imaging (MRI) that also suggest a diagnosis of NF-1. A review
      of 281 NF-1 children with brain MRI results demonstrates the presence of these
      abnormalities in 57% of the cases. It is suggested that this MRI abnormality is
      sufficiently specific to add this feature to the list of diagnostic criteria.
      When MRI findings are present in a child with optic glioma and without skin
      lesions, counseling should be given for NF-1. It is noteworthy that these typical
      MRI findings in NF-1 are less common in adulthood, apparently because of
      spontaneous resolution.

PMID- 9568929
TI  - Neurenteric cyst mimicking pleurodynia: an unusual case of thoracic pain in a
      child.
AB  - This study reports an 8-year-old boy with chronic recurring thoracic pain.
      Magnetic resonance imaging of the spine revealed an intradural cyst at T1-T2.
      Despite severe compression of the spinal cord, there was no neurologic deficit.
      After minimally invasive cystectomy, the patient recovered completely.
      Histological examination established the diagnosis of a neurenteric cyst. The
      clinical, pathohistologic, and radiologic aspects are discussed, and the decisive
      role of magnetic resonance imaging in the diagnosis of intraspinal cyst is
      emphasized.

PMID- 9568931
TI  - Cannabis and brain function.
AB  - Current literature and practice experience has been reviewed to clarify what is
      known about the effects of cannabis on brain function, the risk that cannabis use
      may pose for young people during their adolescence, and risk factors within the
      individual or their environment that may predispose to long-term abuse and
      dependence. There is sound evidence that cannabis intoxication has an adverse
      effect on cognitive function and behaviour, and may, in vulnerable individuals,
      lead to a psychotic reaction. Regular use may have an adverse effect on learning,
      with possible mid- to long-term psychological and cognitive impairment. Heavy use
      may lead to emotional dependence with consequent social and psychological
      dysfunction. Intervention strategies must go beyond the conventional education
      and public health measures that appear to have been unsuccessful so far in
      influencing cannabis use in teenagers. Such strategies may more usefully aim at
      assessment of risk factors in individuals and groups for dependence on the drug,
      and the combined and cooperative intervention of parents, schools, health
      professionals and teenagers themselves.

PMID- 9568930
TI  - Phenotypic differences between T-->C and T-->G mutations at nt 8993 of
      mitochondrial DNA in Leigh syndrome.
AB  - This study reports on a patient with Leigh syndrome with a T-to-C mutation at
      nucleotide 8993 of mitochondrial deoxyribonucleic acid (T8993C). The authors
      reviewed 10 Leigh syndrome patients, including ours, with T8993C. Compared with
      18 reported patients with Leigh syndrome caused by a T-to-G mutation at
      nucleotide 8993 (T8993G), Leigh syndrome with T8993C was characterized by a
      significantly higher frequency of ataxia (P < 0.01). None of the reviewed T8993C
      associated Leigh syndrome patients had retinitis pigmentosa, which is one of the
      characteristic findings in Leigh syndrome with T8993G. The milder symptoms of
      T8993C-Leigh syndrome can be explained by the milder complex V dysfunction;
      however, the higher frequency of ataxia in T8993C-Leigh syndrome requires more
      study.

PMID- 9568932
TI  - Cortical malformations: a significant cause of paediatric neurological morbidity.
AB  - Disorders of cortical development are a significant cause of epilepsy,
      developmental delay and congenital neurological deficits in children of all ages.
      Disruption of neuronal proliferation, differentiation, migration and organization
      during the middle trimester are recognized as the basis of most of these
      disorders. With advances in magnetic resonance imaging and increasing recognition
      of the characteristic radiological appearance of these lesions, a variety of
      lesions are now described. Furthermore, detailed clinical and genetic studies
      have lead to the recognition of clinicopathological syndromes of cortical
      maldevelopment with specific modes of inheritance. Our understanding of these
      disorders is increasing rapidly and will continue to do so with improvements in
      neuroimaging, advances in developmental neurobiology and heightened clinician
      awareness.

PMID- 9568933
TI  - Use of aciclovir in herpes simplex virus infections.
AB  - Herpes simplex virus type 1 and type 2 cause a wide range of illnesses ranging
      from minor cold sores to severe necrotising encephalitis or disseminated systemic
      infections seen in immunocompromised patients including neonates. Following
      primary infection, the virus is not eradicated from the body but is latent in
      sensory nerve ganglia where it can reactivate and cause recurrent disease.
      Aciclovir is the most studied and used antiviral agent with activity against
      herpes simplex virus infections. In most situations the use of aciclovir shortens
      the duration of clinical illness and viral shedding and reduces morbidity and
      mortality. All life- or sight-threatening infections should be managed in an
      inpatient hospital setting with intravenous therapy. The use of oral aciclovir is
      recommended in patients with non-life-threatening illness who may still have
      significant symptoms.

PMID- 9568934
TI  - Evidence-based paediatrics.
AB  - Evidence-based medicine is practised widely in some specialties and is now part
      of many undergraduate and graduate medical curricula. However, the extent to
      which it is used in clinical paediatric practice is not known and its expansion
      remains a major challenge. Access to technology which facilitates literature
      searching, and development of journals addressing specific paediatric problems,
      will encourage the use of evidence-based medicine by the busy paediatrician.
      Informed practice of evidence-based medicine will ensure that clinical expertise
      is complemented by a thorough search, evaluation and judicious application of
      relevant information from the medical literature.

PMID- 9568935
TI  - Direct and indirect costs of chickenpox in young children.
AB  - OBJECTIVE: To estimate the medical and economic or societal costs of chickenpox
      in young children using a descriptive study METHODS: Children under 5 years of
      age attending 124 Sydney childcare centres who were reported as having chickenpox
      were studied to assess the costs of medication use and medical consultations,
      days of care missed, and parental costs resulting from lost time from work and
      alternate childcare costs. RESULTS: There were 174 children (92 girls and 79
      boys; in three the sex was not stated) who missed a mean of 5.5 days of care
      because of chickenpox, currently valued at $154. Medical costs were valued at $33
      per child, based on 0.97 medical visits, and topical and oral medication. Labour
      costs resulting from parental work absenteeism were valued at $160 or $345
      depending on the method of calculation, whilst direct economic costs of $24 were
      incurred through use of alternate childcare arrangements. Total costs including
      those incurred by secondary cases and by rare hospitalisations were in the range
      of $393-$578 per affected child. CONCLUSIONS: Medical costs of chickenpox in
      children are small relative to costs incurred as a result of parental work
      absenteeism and to costs of foregone childcare. Ascribing precise work-related
      costs should take into account some capacity to make up lost work time. Such data
      will be required when determining the cost-benefit of childhood varicella
      immunisation.

PMID- 9568936
TI  - Body fat estimation in children by magnetic resonance imaging, bioelectrical
      impedance, skinfold and body mass index: a pilot study.
AB  - OBJECTIVE: The aim of this study was to identify the clinical method to estimate
      body fat which gave best correlation of total body fat and percentage body fat as
      measured on MRI. METHODS: Magnetic resonance imaging (MRI) was used to estimate
      the total body fat volume and percentage body fat and this was compared with
      assessment by bioelectrical impedance (BEI), skinfold thickness and body mass
      index (BMI) in 8- to 12-year-old children. RESULTS: Total body fat measured on
      magnetic resonance imaging (TBF-MRI) significantly correlated with body mass
      index, triceps and subscapular skinfolds, and percentage body fat estimations by
      BEI. Multiple regression analysis showed that BMI and BEI together gave the best
      prediction of total body fat as measured on MRI from the equation: TBF-MRI=
      25277.77+1457.61(BMI)+423.95(%fat-BEI), with R2=0.89. Percentage body fat
      measurement from MRI, BEI and skinfold were not significantly different but their
      results were not interchangeable. Linear regression of %body fat from MRI on
      those obtained from BEI and skinfold measurements showed a modest fit with
      R2=0.6973 and 0.5501, respectively. CONCLUSIONS: In children 8-12 years old, BMI
      gives a good estimation of the total body fat as measured on MRI. The estimation
      will be improved when both BEI and BMI are used in the prediction. Bioelectrical
      impedance has a low correlation with total body fat and its use alone in
      estimating total body fat is not recommended. Skinfold measurement also gives a
      reasonably good prediction of total body fat and addition of BMI and BEI does not
      improve the prediction. Both BEI and skinfold measurements give a modest
      prediction of %body fat measured by MRI method.

PMID- 9568937
TI  - Behaviour of children associated with parental participation during induction of
      general anaesthesia.
AB  - OBJECTIVE: To evaluate children's behaviour during induction of general
      anaesthesia with parental participation. METHODS: A descriptive observational
      study in which the behaviour of the children was assessed using a Global Mood
      Scoring system before and during the induction of general anaesthesia, with their
      parents participating at induction. RESULTS: Parental participation in
      anaesthetic induction was beneficial in avoiding distress at parental separation
      without the use of preoperative sedation. Negative effects of parental
      participation were not encountered. CONCLUSIONS: Parental participation in
      anaesthetic induction of children can reduce distress at parental separation
      without any negative consequences. With proper preparation and education, parents
      should be encouraged to be present during the induction of general anaesthesia.

PMID- 9568938
TI  - Retinopathy of prematurity in infants <29 weeks' gestation at birth in New South
      Wales from 1986-92.
AB  - OBJECTIVE: To study the effect of increased survival of infants <29 weeks'
      gestation on the incidence and severity of retinopathy of prematurity (ROP).
      METHODOLOGY: Review of prospective records from 1986 to 1992 kept in the New
      South Wales (NSW) NICUS database on infants admitted to the neonatal intensive
      care units (NICU) in NSW. The survival rate and the incidence and severity of ROP
      on all infants <29 weeks' gestation admitted to the NICUs in NSW from 1 July 1986
      to 31 December 1987 were compared to a similar group of infants admitted from 1
      January 1992 to 31 December 1992. RESULTS: There was a significant difference in
      the survival rate of infants admitted between the two periods (235 of 376, 62.5%
      survival vs 255 of 336, 75.9% survival, respectively, P<0.0001). The odds ratio
      for survival adjusted for gestational age in the second period was 1.76 [1.24,
      2.48 (95% confidence interval), P<0.002]. There was a slight increase in ROP in
      the second period (79 of 172 examined, 45.9% ROP vs 133 of 238 examined, 55.8%
      ROP, respectively). There was a rise in the number of infants with Stage 3 ROP in
      the second time period (14 of 172 examined, 8.1% ROP vs 41 of 238 examined, 17.2%
      ROP, respectively). However, fewer infants had detached retinas or > or = Stage 4
      ROP in the second group [7 of 172, (4.1 %) vs 3 of 238, (1.3%), respectively].
      This may be a reflection of the increase in the use of cryo- or laser therapy for
      Stage 3 ROP with 'plus' disease [2 of 172 examined, (1.2%) vs 18 of 238 examined,
      (7.6%), respectively]. CONCLUSIONS: With the increase in survival of the very
      preterm infant in recent years, there has been an increase in severe ROP (> or =
      Stage 3) in NSW. Despite the increased survival of the highest at-risk group (24-
      to 26-week gestation infants), there have been fewer cases of retinal detachment.
      There was also a rise in the number of infants receiving cryo- or laser therapy
      intervention.

PMID- 9568939
TI  - Evolution of sleep-disordered breathing and sleep in infants.
AB  - OBJECTIVE: The evolution of sleep-disordered breathing and sleeping patterns in a
      group of high-risk infants was studied throughout the first year of life.
      METHODOLOGY: Eleven infants with documented sleep apnoea underwent overnight
      polysomnographic studies at monthly intervals to 6 months, then at 9 and 12
      months of age. RESULTS: All infants had central apnoea and obstructive events
      recorded on their initial sleep studies. The sleep-disordered breathing in these
      infants was associated with disturbed sleeping patterns. The amount of rapid eye
      movement (REM) sleep recorded in each study was inversely proportional to the
      amount of apnoea. The amount of apnoea and sleep disturbances were highest at 2
      months of age and then progressively improved and obstructive events resolved by
      1 year of age. CONCLUSIONS: The respiratory abnormalities and sleep disturbances
      peaked in severity at the age reported to have the highest incidence of sudden
      infant death syndrome (SIDS) and may have implications for its aetiology.

PMID- 9568940
TI  - Cryptorchidism associated with meningomyelocele.
AB  - OBJECTIVE: The authors studied 75 male infants with meningomyelocele (MMC) to
      analyse the association with cryptorchidism. METHODS: All infants were diagnosed
      at birth and surgically corrected after 24-48 h. Testes were classified
      undescended in accordance with Kaplan. The associated malformations, the exact
      levels of the lesion (surgical report) and the presence of hydrocephalus and the
      cremasteric reflex have each been assessed. RESULTS: In these patients a higher
      incidence of cryptorchidism (14.8%) was found than in the normal population.
      Lesion level (L2-L3) and absence of cremasteric reflex was higher in children
      with associated cryptorchidism. Infants with MMC and undescended testes showed no
      increased incidence of hydrocephalus and sexual hormone levels remained within
      the normal range. These results suggest that the cremaster muscle could be a
      major factor involved in testis descent through the inguinal canal. CONCLUSIONS:
      The authors propose that spinal cord lesion, as well as neurologic dysfunction,
      is of major importance in the pathophysiology of cryptorchidism in spina bifida.

PMID- 9568941
TI  - Prevalence and risk factors of childhood asthma, rhinitis and eczema in Hong
      Kong.
AB  - OBJECTIVE: To assess the prevalence and risk factors of childhood asthma and
      allergies in Hong Kong and compare with that in Singapore and Great Britain.
      METHODOLOGY: Parents of 3618 randomly selected 6- to 7-year-old children
      responded to a questionnaire prepared by the International Study of Asthma and
      Allergies in Childhood (ISAAC) together with supplementary questions on risk
      factors. RESULTS: The 12-month prevalences of wheezing, rhinitis symptoms and
      itchy rash were 9.2%, 35.1% and 4.2%, respectively. Wheezing in the past year was
      significantly associated with rhinitis symptoms in the past year, itchy rash in
      the past year, rhinitis interfering with daily activities moderately or severely,
      kept awake by itchy rash in the past year, parental wheezing (one or both
      parents), frequent upper respiratory tract infections (URTI), born in Hong Kong
      and male sex. For girls, the prevalence of wheezing in the past year was lowest
      when they were born in July/August and highest when born in January/February.
      CONCLUSIONS: The prevalence of allergic disorders in Hong Kong was comparable to
      that in Singapore and Great Britain. Several potential risk factors such as
      parental wheezing, frequent URTI, born in Hong Kong, male sex and month of birth
      in girls were identified.

PMID- 9568942
TI  - Adenosine in the management of supraventricular tachycardia in children.
AB  - OBJECTIVE: To assess the efficacy and safety of adenosine in the management of
      supraventricular tachycardia in children. METHODOLOGY: A review of 43 children
      with supraventricular tachycardia who received intravenous adenosine between June
      1992 and July 1995. RESULTS: Thirty-five patients had re-entrant supraventricular
      tachycardia and eight patients had atrial tachydysrhythmias. Reversion to sinus
      rhythm occurred in 75% of episodes in all patients treated for supraventricular
      tachycardia, and in 96% of episodes in patients with re-entrant supraventricular
      tachycardia. Early re-initiation of supraventricular tachycardia after reversion
      to sinus rhythm occurred in 25% of episodes. Sixteen percent of patients reverted
      with the recommended 0.05 mg/kg starting dose, and 35% reverted with a dose of
      0.1 mg/kg. Four patients were given adenosine as a diagnostic procedure to elicit
      occult pre-excitation. The most common side effects were brief feelings of
      discomfort. No serious side effects occurred. CONCLUSION: Adenosine is safe and
      effective in the management of supraventricular tachycardia in children. A
      commencing dose of 0.1 mg/kg is appropriate.

PMID- 9568943
TI  - Should preterm infants born after 29 weeks' gestation be screened for
      intraventricular haemorrhage?
AB  - OBJECTIVES: To determine whether the current incidence of intraventricular
      haemorrhage (IVH) of grade 2 or more is high enough in preterm infants born after
      29 weeks gestation to justify the cost of screening with ultrasound and to
      explore clinical indicators for risk of IVH in the more mature preterm infant.
      METHODS: This cohort study examined the incidence and severity of IVH in 800
      preterm infants born between January 1992 and August 1996, of whom 436 were born
      after 29 weeks. Demographic and clinical details were collected from a
      prospectively maintained database. The Medicare schedule charge rate for cerebral
      ultrasound was used to calculate costs. RESULTS: 1.1% of preterm babies born
      after 29 weeks gestation who had routine ultrasound scans had an IVH of grade 2
      or 3, no infant had a grade 4 IVH. Two infants had a grade 3 IVH, both of which
      were symptomatic. IVH was poorly predicted by other clinical criteria. Using the
      Medicare schedule to estimate costs, detecting the five grade 2 or 3 IVH cost
      A$42,000. CONCLUSIONS: The incidence of grade 2-4 IVH is low in infants born
      after 29 weeks gestation. Screening of this population is expensive and probably
      not justified. It may be most appropriate to scan these infants only if their
      condition raises concern.

PMID- 9568944
TI  - Short- and long-term neurological outcomes following neonatal chest
      physiotherapy.
AB  - OBJECTIVE: To test the hypothesis that chest physiotherapy in extremely premature
      infants is associated with abnormal neurological outcomes. METHODS: All babies
      born during the years 1992-1994 at gestations of 24-29 weeks who survived to 28
      days were included in the study cohort (n=213). Chest physiotherapy was provided
      by trained physiotherapists for babies with secretions causing obstruction to the
      airway or for babies with evidence of collapse and/or consolidation. The
      relationship between chest physiotherapy and cystic brain lesions at discharge,
      or cerebral palsy (CP) and developmental quotient (DQ) at 1 year corrected age,
      were then explored. RESULTS: Ninety-seven babies (45% of the cohort) received
      physiotherapy. No baby had a brain lesion similar to that described as
      encephaloclastic porencephaly. Babies receiving physiotherapy had significantly
      lower birthweights and gestational ages. Of the 13 babies found to have either
      periventricular leucomalacia or porencephalic cysts, seven (7%) were in the
      physiotherapy group, and six (5%) were in the nonphysiotherapy group. Of the
      babies surviving to 1 year corrected age, 189 (92%) had multidisciplinary follow
      up. Eleven (13%) of the babies who received physiotherapy had suspected CP, and
      14 (13%) of those not receiving physiotherapy had CP. The DQ of those who
      received physiotherapy was 96.0+/-16.6, and 101.6+/-16.6 for those who did not.
      Following adjustment for gestational age and other unequal risk factors using
      logistic regression, none of the above outcomes was significantly associated with
      the number of physiotherapy treatments. CONCLUSION: We could find no evidence
      that chest physiotherapy, as given in our unit, was associated with abnormal
      neurological outcomes in extremely preterm infants.

PMID- 9568945
TI  - Excessive rates of childhood mortality in the Northern Territory, 1985-94.
AB  - OBJECTIVES: To estimate the post-infant/childhood mortality rate (1-14 years) in
      the Northern Territory (NT) of Australia. METHODS: A retrospective study of post
      infant death in the 10 years 1985-94 inclusive in the NT. RESULTS: Two hundred
      and forty-four deaths were identified. Compared to a non-Aboriginal, an
      Aboriginal child was twice as likely to die from accidents, 11 times more likely
      to die from infection and 3.2 times more likely to die from all causes. Road
      traffic accidents were the leading cause of accident mortality in Aboriginal
      children. All children who died in collisions or rollovers were unrestrained.
      Drowning was the major cause of death amongst non-Aboriginal children aged 1-4
      years; none of the residential pools in which drowning occurred had fencing which
      complied with the recommended Australian fencing standards. Mortality rates from
      infection were highest in Aboriginal children aged 1-4 years. The overall
      mortality rate decreased over the 10-year period with a significant reduction in
      non-Aboriginal but not in Aboriginal children. CONCLUSIONS: NT children aged 1-14
      years have higher mortality rates than their Australian counterparts and these
      are significantly higher in Aboriginal compared to non-Aboriginal children.
      Legislation and enforcement of isolation pool fencing, car seat restraints and
      safer driving on rural roads could have a significant impact on reducing accident
      mortality.

PMID- 9568946
TI  - Malnutrition, gastroenteritis and trypsinogen concentration in hospitalised
      Aboriginal children.
AB  - OBJECTIVE: To explore relationships between malnutrition and pancreatic damage in
      hospitalised aboriginal children. METHODS: Immunoreactive trypsinogen (IRT)
      concentrations were measured in two populations of hospitalised aboriginal
      children in Australia: 472 children aged 0-3 years, in Alice Springs (Northern
      Territory); and 187 children aged 0-16 years in Mount Isa (Queensland).
      Correlation of whole blood IRT with height and weight z-scores, four-site
      skinfold thickness and upper arm circumference was sought. RESULTS: In Mount Isa,
      the geometric mean IRT concentration rose with decreasing weight z-score. The IRT
      concentration was otherwise unrelated to nutritional indices. Sixty percent of
      the 39 Mount Isa patients with gastroenteritis and 24.5% of the 358 Alice Springs
      patients with gastroenteritis had an IRT concentration in the upper quartile for
      their population, compared with 16% for patients with other diagnoses in both
      populations. CONCLUSIONS: A high IRT concentration in patients with low weight z
      scores is a confounding effect of gastroenteritis, and may result from
      subclinical pancreatic disease in gastroenteritis.

PMID- 9568947
TI  - The use of lumbar puncture and laboratory tests for sepsis by Australian
      neonatologists.
AB  - OBJECTIVE: To ascertain the current use of lumbar puncture (LP) and laboratory
      tests for possible or suspected sepsis by Australian neonatologists. METHODS: A
      self administered anonymous response questionnaire. RESULTS: Sixty-nine (73%) of
      94 neonatologists responded. None performed LP routinely in preterm infants with
      respiratory distress syndrome (RDS) or asymptomatic term infants with maternal
      Group B streptococcus (GBS) colonisation. One (1.6%) performed LP in term infants
      with respiratory distress, and only 35 (51%) performed LP in preterm infants with
      suspected late-onset sepsis (LOS). Twenty-one percent did not perform LP on all
      preterm infants with RDS and septicaemia and 24% did not perform LP on all
      preterm infants with late-onset septicaemia. Sixty-six percent and 85% did not
      perform LP for laboratory evidence suggestive of sepsis in preterm infants with
      RDS and preterm infants with LOS, respectively. Forty-nine percent investigated
      asymptomatic term infants with maternal GBS colonisation. CONCLUSIONS: Lumbar
      puncture and laboratory tests for possible or suspected sepsis are not used
      uniformly by Australian neonatologists. The presently available information in
      the scientific literature is ambiguous and systematic review and further
      scientific study are required to determine best practice guidelines.

PMID- 9568948
TI  - Bowel dysfunction in cystic fibrosis: importance of breath testing.
AB  - OBJECTIVE: To investigate the prevalence of carbohydrate malabsorption and
      bacterial overgrowth in children with cystic fibrosis (CF) and abnormal stool
      pattern referred for breath hydrogen testing. METHODS: Results from 89 tests
      using lactose, sucrose and lactulose in 54 children with CF were compared with
      5430 tests on children with non-CF-related stool abnormalities. RESULTS: Children
      with CF were more frequently unable to ferment lactulose to hydrogen (39% vs.
      20%, P<0.03); they had significantly longer oro-caecal transit times (mean 99 vs.
      68 min, P<0.0003); they had a higher incidence of bacterial overgrowth (32% vs.
      7%, P<0.003) and sucrose malabsorption (47% vs. 14.5%, P<0.004); but they had no
      increase in lactose malabsorption (40% vs. 31%). Children with bacterial
      overgrowth in both groups had longer transit times (CF 123 min, non-CF 108 min)
      compared to the non-CF children without overgrowth (68 min) and reference normal
      children (69 min). CONCLUSIONS: Bacterial overgrowth and carbohydrate
      malabsorption, particularly of sucrose, should be considered when assessing
      children with CF and abnormal stool patterns.

PMID- 9568949
TI  - Overdose of ergometrine in the newborn infant: acute symptomatology and long-term
      outcome.
AB  - OBJECTIVE: To document the short- and long-term effects of accidental
      administration of ergometrine in adult dosage to the newborn infant. METHODS: The
      case records of all infants admitted to the Royal Children's Hospital (RCH) since
      1970 with a diagnosis of acute ergometrine overdose were reviewed, and details of
      the acute symptomatology, management, and the neurodevelopmental outcome at
      follow-up were noted. Similar information was obtained, where available, from
      previous case reports, and from two major drug information services.
      Additionally, data relating to administration of uterotonic agents and vitamin K
      were collected from tertiary perinatal centres around Australia. RESULTS: Seven
      cases of neonatal ergometrine overdose were identified at RCH. The major features
      of the acute toxicity syndrome were: encephalopathy (100% RCH cases, 79% combined
      cases); seizures (100%, 70%); peripheral vascular disturbances (100%, 83%); and
      oliguria (43%, 34%). Other important symptoms were hypoxaemia, hypertension and
      feed intolerance. 86% of RCH cases (72% overall) required ventilatory support.
      Virtually all symptoms resolved within 4 days, and 86% of RCH infants (86% all
      cases) were neurologically intact at the time of discharge. Long-term
      neurodevelopmental outcome was normal in 100% of RCH infants (n=6). All the
      perinatal centres surveyed give vitamin K in the labour ward soon after delivery,
      and 7 of 18 (39%) reported using Syntometrine (ergometrine 0.5 mg, Syntocinon 5
      IU) routinely during the third stage of labour. Thus the circumstances in which
      ergometrine overdose can occur still exist in many labour wards around the
      country. CONCLUSIONS: Despite the catastrophic initial presentation, the long
      term prognosis after neonatal ergometrine overdose appears to be favourable. To
      prevent further cases of this life-threatening drug error, we recommend that
      administration of vitamin K be deferred until just prior to, or shortly after,
      transfer of the newborn infant to the postnatal ward.

PMID- 9568950
TI  - Osteomyelitis and septic arthritis due to Citrobacter freundii and Haemophilus
      influenzae type b.
AB  - This report describes dual infection with Citrobacter freundii and Haemophilus
      influenzae type b causing septic arthritis and osteomyelitis of the elbow in a
      previously healthy 5-year-old boy. The patient was treated successfully with
      intravenous fosfomycin for 4 weeks. Infections with Citrobacter beyond the
      neonatal period are rare in paediatric patients. When Citrobacter spp. is
      isolated, coinfection with other bacterial pathogens should be considered.

PMID- 9568951
TI  - Agammaglobulinaemia in a girl with a mosaic of ring 18 chromosome.
AB  - A patient with a mosaic karyotype 45,XX,-18/46,XX,dic r(18)/46,XX,r(18) with
      multiple phenotypic abnormalities and immunodeficiency was presented at the age
      of 14 years. Immunological investigation revealed markedly decreased IgG, IgA and
      in two of three evaluations also IgM levels. Although selective IgA deficiency is
      frequent in patients with a ring chromosome 18, this is the third patient
      described with decreased levels of other immunoglobulin isotypes. The association
      of chromosome 18 partial deletions and immunoglobulin abnormalities suggests the
      presence of an as yet unrecognised gene with a pivotal role for immunoglobulin
      production on chromosome 18.

PMID- 9568952
TI  - Meningitis due to Haemophilus influenzae type f.
AB  - OBJECTIVE: To describe a case of Haemophilus influenzae type f (Hif) meningitis
      occurring in the H. influenzae type b (Hib) vaccine era. RESULTS: Successful
      treatment of a case of Hif meningitis in a previously vaccinated 3-year-old girl
      is described. The outcome was complicated by deafness. No underlying
      immunosuppression was demonstrated. CONCLUSIONS: Despite the great success of Hib
      vaccines in reducing invasive disease due to H. influenzae, cases of H.
      influenzae meningitis continue to occur, caused by less common encapsulated
      serotypes. Whether there will be an increase in the number of these cases in the
      vaccine era is unknown and infection due to non-b serotypes requires close
      monitoring.

PMID- 9568953
TI  - Symptomatic zinc deficiency in breast-fed term and premature infants.
AB  - Two 3-month-old exclusively breast-fed infants, one born at full-term and the
      other born prematurely, developed symptomatic zinc deficiency manifested by an
      acrodermatitis enteropathica-like eruption. Inadequate breast milk zinc was
      demonstrated in both cases. A rapid clinical response followed oral zinc
      supplementation after which their serum zinc levels returned to normal. The
      infants remained asymptomatic following cessation of zinc therapy. Reports of
      similar cases suggest that in a group of infants breast milk does not meet their
      nutritional zinc requirements. Inadequate breast milk zinc is thought to result
      from a defect in transfer of zinc from maternal serum to breast milk.

PMID- 9568954
TI  - SIDS and immunization rates in South Australia.

PMID- 9568955
TI  - Early detection of conduct disorder.

PMID- 9568956
TI  - Effects of freezing oral electrolyte solution.

PMID- 9568957
TI  - Virus taxonomy--1997.

PMID- 9568958
TI  - Human recombinant Puumala virus antibodies: cross-reaction with other
      hantaviruses and use in diagnostics.
AB  - A panel of seven human monoclonal Fabs against Puumala virus (PUU) nucleocapsid
      protein (N) was obtained by panning an antibody phage-display library prepared
      from the spleen of a PUU-immune individual. Three antibodies reacted in
      immunoblotting and cross-reacted strongly with Tula and Sin Nombre virus
      recombinant N proteins. These antibodies mapped to the amino terminus of the N
      protein. One PUU glycoprotein 2 (G2)-specific Fab obtained against a novel
      epitope (G2c) cross-reacted with Khabarovsk virus but not with the other
      hantavirus serotypes. An N protein-specific Fab was successfully used as capture
      antibody to detect PUU-specific serum IgG and IgM antibodies in an enzyme
      immunoassay. The result demonstrates the usefulness of recombinant human Fabs as
      potential diagnostic tools.

PMID- 9568959
TI  - Pseudotype formation with La Crosse virus glycoproteins.
AB  - Pseudotype formation is a powerful tool for analysing mechanisms of virus
      neutralization and entry, since it allows for analysis of glycoprotein properties
      without the necessity for preparing recombinant genomes. Using recombinant
      vaccinia viruses, we prepared pseudotypes of La Crosse virus with recombinant
      glycoproteins cloned from the monoclonal antibody (MAb)-resistant variant V31.
      The resulting pseudotypes became partially resistant to MAb 807-31. Furthermore,
      when the V31 glycoproteins were incorporated into a second MAb-resistant variant
      (V33), the pseudotyped virus became sensitive to neutralization by the MAb (807
      33) originally used in its selection. These results suggest a simple technique
      for the incorporation of glycoprotein mutations into bunyaviruses, allowing
      analysis of mechanisms of neutralization and other virus entry functions.

PMID- 9568960
TI  - Nucleotides in the panhandle structure of the influenza B virus virion RNA are
      involved in the specificity between influenza A and B viruses.
AB  - Influenza A and B viruses share common sequences and potentially similar
      panhandle structures in the terminal noncoding regions of virion RNA (vRNA).
      Interesting differences exist, however, in the number of conserved nucleotides at
      the 5' and 3' ends of the vRNAs, in base pairs constituting the panhandle duplex,
      and the length of uridine stretch (U stretch) juxtaposed to the RNA duplex. To
      analyse the contribution of these signals to the specificity between the two
      viruses, a transient ribonucleoprotein transfection method was used for the
      expression of the chloramphenicol acetyltransferase (CAT) reporter gene flanked
      by the noncoding nucleotides derived from influenza B vRNA. While the base
      pairing in the RNA duplex was primarily important for template activity, mismatch
      mutations G11 x G12' and C12 x A13' in the terminal RNA duplex region were
      utilized by influenza B virus, whereas these mutations were detrimental for
      influenza A virus. Different activity profiles were observed in the length
      preference of the RNA duplexes: maximum template activity was observed with 11
      base pairs for influenza B virus, and 8 base pairs for influenza A virus. When
      the mutants with various lengths of U stretch were tested, highest CAT activities
      were observed with 5 to 7 uridine residues in influenza A virus, whereas in
      influenza B virus the activity was drastically decreased with 7 uridine residues.
      We suggest that the specific interaction of influenza virus RNA polymerase with
      these noncoding cis-acting signals in transcription of the RNA genome, along with
      unique coding strategies adopted by influenza B virus, has contributed to the
      divergence of these two closely related viruses.

PMID- 9568961
TI  - Sendai virus-like particles devoid of haemagglutinin-neuraminidase protein infect
      cells via the human asialoglycoprotein receptor.
AB  - Virus-like particles with genetically defined envelope proteins were generated
      from cDNA in order to examine the requirement of Sendai virus haemagglutinin
      neuraminidase (HN) protein for particle formation, and the role of fusion protein
      (F) in receptor binding and membrane fusion. Characterization of particles devoid
      of HN protein showed that particle formation was unimpaired by the absence of HN
      protein, indicating that HN protein is dispensable for virus assembly and
      budding. Infection studies further demonstrated that virus adsorption and
      penetration can be mediated solely by the F protein when the human
      asialoglycoprotein receptor is present at the surface of host cells.

PMID- 9568962
TI  - Immunological basis for protection in a murine model of tick-borne encephalitis
      by a recombinant adenovirus carrying the gene encoding the NS1 non-structural
      protein.
AB  - The humoral immune response to flaviviruses is mainly directed to the major
      envelope protein, E, and a glycosylated non-structural protein, NS1. Cell
      mediated immune responses, however, appear to be directed mainly against non
      structural proteins. Experiments described here show that a defective recombinant
      adenovirus (Rad51) containing the gene encoding the NS1 protein of tick-borne
      encephalitis virus can induce a strong protective immune response against several
      pathogenic tick-borne flaviviruses in an experimental animal model, and can
      enhance the efficacy of conventional vaccine preparations. A protective immune
      response against a lethal virus challenge can also be induced by the passive
      transfer of antibodies, B cells or T cells from animals vaccinated with Rad51.
      Raised levels of non-neutralizing antibodies and cytokines associated with a T
      helper cell-type 1 immune response are also observed. These data demonstrate the
      importance of non-structural viral proteins in the protective immune response
      against flaviviruses and support the use of non-structural viral proteins as
      vaccine components.

PMID- 9568963
TI  - Definition of the region on NS3 which contains multiple epitopes recognized by
      dengue virus serotype-cross-reactive and flavivirus-cross-reactive, HLA-DPw2
      restricted CD4+ T cell clones.
AB  - The epitopes recognized by six CD4+ CD8- cytotoxic T lymphocyte (CTL) clones
      established from a dengue-3 virus-immune donor were defined. (i) Three CTL
      clones, JK10, JK34 and JK39, were cross-reactive for dengue virus types 1-4. (ii)
      One clone, JK28, was cross-reactive for dengue virus types 1-4 and West Nile
      virus. (iii) Two clones, JK26 and JK49, were cross-reactive for dengue virus
      types 1-4, West Nile virus and yellow fever virus. The clones, except for JK49,
      recognized the same epitope on NS3 in an HLA-DPw2-restricted fashion. The
      smallest synthetic peptide recognized by the five CTL clones was a 10 aa peptide
      which comprises aa 255-264 on dengue virus NS3. JK49 recognized the overlapping
      epitope which comprises aa 257-266 in an HLA-DPw2-restricted fashion. Analysis of
      T cell receptor (TCR) usage by these T cell clones revealed that (i) JK10 and
      JK34 use V alpha11, and JK34 and JK28 use V beta23, and (ii) the amino acid
      sequences of the V(D)J junctional region of the TCR were different among these
      five CTL clones. There were, however, single amino acid conservations among TCRs
      of some of these T cell clones. These results indicate that the region on NS3
      which comprises aa 255-266 contains multiple epitopes recognized by dengue
      serotype-cross-reactive and flavivirus-cross-reactive CD4+ CTL in an HLA-DPw2
      restricted fashion and that a single epitope can be recognized by T cells which
      have heterogeneous virus specificities.

PMID- 9568964
TI  - Low level or absent in vivo replication of hepatitis C virus and hepatitis G
      virus/GB virus C in peripheral blood mononuclear cells.
AB  - To investigate which subsets of peripheral blood mononuclear cells (PBMCs) are
      susceptible to infection with hepatitis C virus (HCV) and hepatitis G virus (HGV)
      or GB virus C (GBV-C), a PCR-based assay using tagged primers in the core region
      (HCV) and NS3 region (HGV/GBV-C) for the specific detection of negative strand
      (replicating) viral RNA sequences was developed. In liver biopsy samples both
      positive and negative strands of HCV RNA were detected, at levels ranging from 3
      to 11 x 10(6) RNA copies per 10(6) cells and 3.7-4.2 x 10(3) copies per 10(6)
      cells respectively, while lower frequencies of positive strands of GBV-C/HGV RNA
      were detected (from 13 biopsies, the highest frequency was 7.3 x 10(3) per 10(6)
      cells). In no samples were negative RNA strands detected. To investigate extra
      hepatic replication of HCV and GBV-C/HGV, CD4+, CD8+ and B lymphocytes, monocytes
      and putative dendritic cell populations were separated from PBMCs from ten study
      subjects. Detection of positive strand HCV RNA was largely confined to B
      lymphocytes (at levels of up to 5 x 10(3) copies per 10(6) cells), while
      detection of negative strands was confined to a single subset (dendritic cells)
      of one of the study individuals. Similarly, GBV-C/HGV was detected at low levels
      in only twelve of twenty PBMC samples, while negative strands were uniformly
      absent. The low levels of HCV and GBV-C/HGV RNA in PBMCs suggest that these cells
      are at most a minor reservoir for virus replication. The absence of detectable
      replication of GBV-C/HGV suggests that the actual site of GBV-C/HGV replication
      remains to be discovered.

PMID- 9568965
TI  - A common RNA motif in the 3' end of the genomes of astroviruses, avian infectious
      bronchitis virus and an equine rhinovirus.
AB  - In the 3' non-coding region of the genomes of infectious bronchitis virus, an
      avian coronavirus and the picornavirus equine rhinovirus serotype 2, there is a
      motif with remarkable similarity, both in sequence and folding, to the second RNA
      stem-loop from the 3' end of the genomes of human astroviruses. This motif was
      also found in astroviruses of sheep, pig and turkey, suggesting that it is a
      common feature of all astroviruses. The conserved nature of the motif indicates
      that there has been strong selection for its preservation. There is significant
      homology between the regions flanking this motif in infectious bronchitis virus
      and a continuous RNA sequence at the same distance from the 3' poly(A) tail in
      some related mammalian coronaviruses. These observations suggest that the
      presence of the motif in these three viral families is the result of at least two
      separate RNA recombination events.

PMID- 9568966
TI  - Induction of protective immunity in chickens vaccinated with infectious
      bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus.
AB  - A recombinant baculovirus containing the S1 glycoprotein gene of the virulent
      nephropathogenic KM91 strain of infectious bronchitis virus (IBV) was constructed
      in order to investigate protective immunity in vaccinated chickens. Results from
      the protection test were evaluated by re-isolation of virus from the kidneys and
      tracheas of vaccinated chickens after challenge with strain KM91. After three
      immunizations, the recombinant S1 (rS1) glycoprotein induced 50% protection of
      the kidney, whilst inactivated KM91 induced 88% and 50% protection of the kidney
      and trachea, respectively. In chickens primed with the attenuated H120 vaccine
      strain, which is heterologous to KM91, the rS1 glycoprotein induced 83%
      protection of the kidney after two immunizations. Haemagglutination-inhibition
      titres were also increased in chickens immunized with the rS1 glycoprotein after
      three immunizations, and significantly higher titres were detected after
      challenge. These data indicate that the expressed rS1 glycoprotein alone can
      induce a protective immune response as well as an antibody response.

PMID- 9568967
TI  - Identification of mutations in the rotavirus protein VP4 that alter sialic-acid
      dependent infection.
AB  - To explore further the role of VP4 as the rotavirus cell attachment protein, VP7
      monoreassortants derived from the sialic-acid-dependent simian strain RRV and
      from the sialic-acid-independent human strains D, DS-1 and ST-3 were tested for
      susceptibility of infectivity of neuraminidase-treated MA-104 cells. Infectivity
      of RRV x D VP7 and RRV x ST-3 VP7 monoreassortants decreased when sialic acid was
      removed from the cell surface. However, of three separate RRV x DS-1 VP7
      monoreassortants tested, only one was sialic-acid-dependent. Sequence analysis
      showed that both sialic-acid-independent strains contained a single amino acid
      change, Lys to Arg, at position 187. In addition, sialic-acid-independent
      infectivity was seen in one of 14 RRV VP4 neutralization escape mutants tested,
      and this strain was found to have a Gly to Glu change at amino acid position 150.
      These results indicate that positions 150 and 187 of VP4 play an important role
      in early rotavirus-cell interactions.

PMID- 9568968
TI  - Antimicrobial peptides melittin and cecropin inhibit replication of human
      immunodeficiency virus 1 by suppressing viral gene expression.
AB  - Antimicrobial peptides are effectors of innate immunity, providing their hosts
      with rapid non-specific defence against parasitic invaders. In this report, the
      effects are assessed of two well-characterized antimicrobial amphipathic peptides
      (melittin and cecropin) on human immunodeficiency virus 1 (HIV-1) replication and
      gene expression in acutely infected cells at subtoxic concentrations. Production
      of infectious, cell-free virus was inhibited in a dose-dependent manner, with
      ID50 values in the range 0.9-1.5 microM for melittin and 2-3 microM for cecropin.
      Analysis of the effect of melittin on cell-associated virus production revealed
      decreased levels of Gag antigen and HIV-1 mRNAs. Transient transfection assays
      with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that
      melittin has a direct suppressive effect on activity of the HIV LTR. HIV LTR
      activity was also reduced in human cells stably transfected with retroviral
      expression plasmids for the melittin or cecropin gene. It is concluded that
      antimicrobial peptides such as melittin and cecropin are capable of inhibiting
      cell-associated production of HIV-1 by suppressing HIV-1 gene expression.

PMID- 9568969
TI  - Replication of human immunodeficiency virus type 1 (HIV-1), simian
      immunodeficiency virus strain mac (SIVmac) and chimeric HIV-1/SIVmac viruses
      having env genes derived from macrophage-tropic viruses: an indication of
      different mechanisms of macrophage-tropism in human and monkey cells.
AB  - To investigate the transferability of macrophage (Mphi)-tropism among primate
      lentiviruses, we constructed recombinants of human immunodeficiency virus type 1
      (HIV-1), simian immunodeficiency virus strain mac (SIVmac) and chimeric HIV
      1/SIVmac (SHIV) having env region Mphi-tropic determinants. A recombinant HIV-1
      having env partially derived from a Mphi-tropic HIV-1 strain (JR-FL) replicated
      in human macrophages but not in monkey macrophages. Conversely, a recombinant
      SIVmac having env from a Mphi-tropic strain (SIVmac316) replicated in monkey
      macrophages but not in human macrophages. A new SHIV (designated NM-3rN/JRFL)
      carrying the LTR and gag, pol, vif, vpx and nef of SIVmac and vpr, tat, rev, vpu
      and env of HIV-1 with env partially replaced by that of JR-FL was replication
      competent in human macrophages but not in monkey macrophages. These results
      suggest that the Mphi-tropic determinant is specific to each host species and
      that the mechanism of Mphi-tropism is different between HIV and SIV.

PMID- 9568970
TI  - Endotoxin treatment of equine infectious anaemia virus-infected horse macrophage
      cultures decreases production of infectious virus.
AB  - Lentiviruses replicate in cells of the immune system, and activation of immune
      cells has been shown to modulate virus replication. To determine the effects of
      macrophage activation on replication of equine infectious anaemia virus (EIAV),
      primary horse macrophage cultures (HMCs) were established from 20 different
      horses, infected with an avirulent strain of EIAV, and stimulated with 5
      microg/ml of bacterial endotoxin. Supernatants collected from HMCs were assayed
      for the presence of tumour necrosis factor (TNF-alpha) and for production of
      infectious virus. Results indicated that EIAV replication in vitro varied
      significantly (P < or = 0.0001) from horse to horse, regardless of the treatment
      of HMCs. Also, EIAV replication was significantly (P < or = 0.0001) decreased in
      HMCs stimulated with bacterial endotoxin as compared to untreated HMCs. No
      significant correlation was found between virus replication and production of TNF
      alpha following treatment of virus-infected cells with bacterial endotoxin.
      However, when HMCs were treated with endotoxin prior to virus infection,
      inhibition of EIAV replication was proportional to increasing levels of
      endotoxin. PCR and RT-PCR were used to amplify EIAV proviral DNA and mRNA
      sequences, respectively, at various time-points following infection. The results
      indicated that the early events of EIAV replication, up to and including
      transcription of multiple-spliced mRNAs, were not inhibited by treatment of EIAV
      infected macrophages with bacterial endotoxin. This suggests that endotoxin
      treatment inhibits a posttranscriptional step in the virus replication cycle.

PMID- 9568971
TI  - Antigenic variants of J subgroup avian leukosis virus: sequence analysis reveals
      multiple changes in the env gene.
AB  - HPRS-103, the prototype of avian leukosis virus (ALV) subgroup J, was isolated in
      1989 from meat-type chickens from commercial flocks where it induces myelocytic
      myeloid leukosis (ML). The HPRS-103 env gene differs considerably from other ALV
      subgroups but shows high identity (75-97%) to env-like sequences of the different
      members of the EAV family of endogenous avian retroviruses. Recently, we have
      isolated several viruses related to HPRS-103 from cases of ML. Although these
      isolates showed properties of ALV subgroup J, the majority of them resisted
      neutralization by HPRS-103-specific serum, suggesting antigenic variation. The
      nucleotide sequence of the env gene of the variant viruses showed several
      substitutions resulting in amino acid changes especially clustered in the
      variable regions hr1, hr2 and vr3. Analysis of the data suggests that selection
      pressure, probably from the immune response, is driving the antigenic variation
      among the isolates. Phylogenetic analysis of the sequences showed the
      evolutionary relationships of the isolates with HPRS-103 and the EAV family of
      endogenous avian retroviruses. The epidemiological significance of the antigenic
      variation and the emergence of variant viruses are discussed.

PMID- 9568972
TI  - Properties of tumour suppressor p53 in murine hepatocyte lines transformed by
      hepatitis B virus X protein.
AB  - Persistent infection by hepatitis B virus (HBV) correlates with the prevalence of
      hepatocellular carcinoma. It has recently been demonstrated that the complete
      viral genome very efficiently transforms the immortalized murine hepatocyte line
      FMH202 in vitro. Here it is shown that the viral transactivating protein X (HBx)
      is sufficient to transform FMH202 cells, albeit with lower efficiency. Clonal
      cell lines expressing HBx mRNA in moderate or high amounts grew in soft agar and
      formed tumours in nude mice. Growth efficiency in soft agar of HBx transformed
      cell lines was much lower than that of cell lines transformed with the complete
      genome, and latency of tumour induction in nude mice was significantly longer
      after inoculation of HBx than of HBV transformed FMH202 cell lines. A marker of
      complete transformation, p53, was found to be phosphorylated more strongly in HBx
      transfected cell lines than in controls, and a cellular kinase was found to be
      associated with p53 complexes from HBx transformed cell lines. p53 was of wild
      type conformation and was located in the nucleus of transformed cells.

PMID- 9568973
TI  - Detection of new human papillomavirus sequences in skin lesions of a renal
      transplant recipient and characterization of one complete genome related to
      epidermodysplasia verruciformis-associated types.
AB  - Human papillomavirus (HPV) DNA, originally isolated from patients suffering from
      the skin disease epidermodysplasia verruciformis (EV), and a growing number of
      related sequences have recently been detected in a high percentage of benign and
      malignant skin lesions of both immunosuppressed and immunocompetent people. HPV
      L1 DNA fragments (374-389 bp long) from a solar keratosis and a squamous cell
      carcinoma (SCC) of a renal transplant recipient were amplified, cloned and
      sequenced. In 54 clones, six different HPV sequences were identified. One of
      these six corresponded to the known type HPV-8 and two (RTRX3 and RTRX7) have
      been described previously in cutaneous lesions of immunosuppressed patients. The
      remaining three sequences were different from all known HPV types: an HPV-9
      related sequence (77.4% identity), an RTRX2-related sequence (82.6% identity),
      and an HPV-22-related sequence (83.7% identity). These three sequences,
      representing putatively new HPV types, were named RTRX8, RTRX9 and RTRX10,
      respectively. RTRX7 was found in the majority of clones from both lesions. The
      complete genome of RTRX7 (7731 bp) was cloned as six overlapping subgenomic
      fragments, generated by nested PCR with DNA extracts from the SCC. RTRX7 showed a
      genome organization typical of HPVs associated with EV. The L1 DNA sequence
      differed by 15% from the corresponding region of its closest known relative, HPV
      12; thus, RTRX7 can be regarded as a new HPV type. RTRX7 DNA could not be
      detected by Southern blot hybridization with the homologous probe, indicating
      that the DNA concentration was below one copy per 10 cells in the investigated
      SCC.

PMID- 9568974
TI  - Human polyomavirus JC control region variants in persistently infected CNS and
      kidney tissue.
AB  - The question of a possible role for JC virus (JCV) genomic rearrangements in the
      pathogenesis of progressive multifocal leukoencephalopathy (PML) was addressed by
      analysis of the genomic complexity and the transcriptional control region (TCR)
      of the JCV DNA population in persistently infected CNS and kidney tissue. After
      cloning of full-length viral DNA, no extensive changes were detected in the
      coding regions of the JCV genome by restriction analysis suggesting an intact JCV
      DNA population. For further analysis of the distribution of JCV subtypes, the non
      coding region was amplified by PCR. Molecular analysis revealed homogeneous JCV
      TCR populations in almost 50% of the individuals. Heterogeneity was found in two
      CNS samples with three and five different JCV subtypes, respectively, and in four
      kidney specimens with two TCR subtypes. Altogether, seven TCR subtypes were
      identified. One in each group represented single promoter element TCRs without
      duplication of sequences. The TCR of the major variant JCV-W1 was comparable in
      sequence and structure to that of the PML prototype JCV Mad-1 DNA. The
      identification of dominant PML-derived JCV TCR subtypes in most persistently
      infected individuals suggests that rearrangements of the JCV TCR can be
      associated with the persistent state of infection. However, it appears unlikely
      that PML-associated JCV subtypes are generated anew in each individual host in
      the course of persistence. The findings rather suggest that a limited number of
      stable JCV subtypes circulate in different geographical regions of the world.

PMID- 9568976
TI  - Glycoprotein C-deficient mutants of two strains of herpes simplex virus type 1
      exhibit unaltered adsorption characteristics on polarized or non-polarized cells.
AB  - Mutants of herpes simplex virus type 1 (HSV-1) strain SC16, lacking each of the
      dispensable glycoproteins C, G, E, I or J, were examined for their ability to
      infect the apical or basolateral surfaces of polarized human epithelial cells.
      None of the mutants was significantly different from the wild-type parent when
      assayed on either surface. Since a previous report had demonstrated that
      glycoprotein C (gC) was necessary for the infection of apical surfaces of
      polarized epithelium, a second gC-negative mutant was constructed on a background
      of HSV-1 strain HFEM. This mutant displayed no phenotype when assayed on the
      apical surface. Furthermore, neither gC-negative mutant differed from its wild
      type parent in its adsorption kinetics or specific infectivity on non-polarized
      Vero cells, a result which is inconsistent with the view that interactions
      between gC and cell surface proteoglycans constitute the initial adsorption
      process. Our findings thus conflict with previous reports and suggest that
      proposed functions of HSV-1 gC in the infection of polarized and non-polarized
      cells may be strain-dependent.

PMID- 9568975
TI  - JC virus Type 1 has multiple subtypes: three new complete genomes.
AB  - The complete genomes of three new Type 1 strains of JC virus (JCV) from urine
      have been analysed. These were subtype 1A, subtype 1B and Type 4 as assigned from
      a short typing fragment in the VP1 gene. They differ from Mad1 (subtype 1A) by
      less than 1.0% of the DNA sequence. Based on its complete genome, the JCV Type 4
      strain falls into a Type 1 subgroup. Type 4, with several Type 3-like sites in
      the short typing fragment, is a possible recombinant strain. The consensus of
      Type 1 DNA sequences is distinguished within the coding region from both Type 2
      (strain GS/B) and five Type 3 (African and African American) strains at 64 sites.
      Most mutations are silent, but at 21 positions amino acid changes occur. Our
      findings define the subtypes of JCV Type 1 and support the validity of genotyping
      within the short VP1 fragment.

PMID- 9568977
TI  - Characterization of the protein encoded by gene UL49A of herpes simplex virus
      type 1.
AB  - Herpes simplex virus type 1 (HSV-1) gene UL49A potentially encodes a primary
      translation product of 91 residues with a signal sequence at the N terminus and a
      membrane anchor domain near the C terminus. Mutants were generated in this gene
      and utilized to characterize the encoded protein on SDS-PAGE as a 6.7 kDa species
      which fractionated with infected cell membranes, was a relatively abundant virion
      component, and was not detectably O-glycosylated. The protein was identified by
      microsequencing as a 68 residue polypeptide formed by removal of 23 residues from
      the N terminus of the primary translation product. Cleavage of the signal
      sequence was also demonstrated by in vitro transcription and translation in the
      presence of microsomal membranes. The UL49A protein was efficiently solubilized
      along with envelope proteins by treatment of virions with a non-ionic detergent
      but only in the presence of a reducing agent, suggesting that it may be an
      envelope protein that is disulphide-linked to the tegument. It is apparent from
      mutational analysis that the 10 amino acid residues at the C terminus are not
      essential for synthesis of the protein, signal sequence cleavage, targeting to
      membranes and virions, linkage to the tegument and growth of virus in cell
      culture.

PMID- 9568978
TI  - Mice lacking inducible nitric-oxide synthase are more susceptible to herpes
      simplex virus infection despite enhanced Th1 cell responses.
AB  - Mice deficient in the inducible nitric-oxide synthase (iNOS), constructed by gene
      targeting, were significantly more susceptible to herpes simplex virus (HSV)-1
      infection, displayed a delayed clearance of virus from the dorsal root ganglia
      (DRG) and exhibited an increase in the frequency of virus reactivation in DRG
      compared with similarly infected heterozygous mice. The infected iNOS-deficient
      mice developed enhanced Th1-type immune responses and their spleen cells produced
      higher concentrations of IL-12 than similarly infected heterozygous mice. This
      finding suggests that iNOS plays an important role in resistance against HSV-1
      infection. Furthermore, nitric oxide (NO) may block the development of Th1 cells
      via inhibition of IL-12 synthesis and thereby play a role in immune regulation.

PMID- 9568980
TI  - Open reading frame L1 of Marek's disease herpesvirus is not essential for in
      vitro and in vivo virus replication and establishment of latency.
AB  - Two mutant CV1988 Marek's disease virus (MDV) strains were developed in which a
      part of ORF L1 was replaced by lacZ with the SV40 early promoter. These mutant
      strains, CVIL1LacZ-A and -B, were inoculated into chickens to test the hypothesis
      that ORF L1 is involved in the induction and/or maintenance of latency. Mutant
      virus could be reisolated from lymphocytes obtained from chickens during both the
      lytic and latent phase of infection, indicating that ORF L1 is not essential for
      the induction and/or maintenance of latency or the reactivation from latency.
      Beta-galactosidase-positive lymphocytes were detected during the latent infection
      demonstrating that the SV40 early promoter can be active in recombinant MDV
      strains during latent infection. Although the insertion of lacZ was stable in
      cell culture, recombination within lacZ and the BamHI-L fragment was observed
      during in vivo infection.

PMID- 9568979
TI  - Intradermal immunization with a bovine herpesvirus-1 DNA vaccine induces
      protective immunity in cattle.
AB  - Although intramuscular (i.m.) injection of DNA encoding glycoprotein D (gD) of
      bovine herpesvirus-1 (BHV-1) induces immune responses in cattle, this route of
      delivery is inefficient. Here we assessed three parameters that may enhance the
      efficacy of a gD DNA vaccine in cattle. First, the immune response generated by
      i.m. injected plasmid expressing a secreted form of gD (tgD) was determined and
      found to be very similar in magnitude to the response induced by gD-expressing
      plasmid. Secondly, gD- and tgD-expressing plasmids were administered by
      intradermal (i.d.) immunization, which resulted in a superior immune response to
      the secreted form, but no improvement in the response to the membrane-associated
      form. However, the form of gD used for immunization did not influence the
      immunoglobulin subtype, the ratio of antigen-specific IgG1 to IgG2 being
      approximately 4:1. Finally, the effect of promoter strength was assessed by
      replacing the Rous sarcoma virus (RSV) promoter, which was used in the original
      experiments, with the human cytomegalovirus immediate early promoter and first
      intron A (HCMV/IA). Although upon transfection in vitro the HCMV/IA promoter
      appeared to be stronger than the RSV promoter, there was only a 2-fold higher
      antibody response in vivo upon i.d. injection of cattle. Protection against virus
      challenge was obtained in the calves immunized i.d. with tgD-encoding plasmid, as
      shown by a significant reduction in weight loss, virus excretion, temperature
      response and clinical disease. No significant protection was observed in the
      animals vaccinated i.d. with the gD-expressing plasmid, which correlates with the
      lower level of immunity pre-challenge.

PMID- 9568981
TI  - Different point mutations within the conserved N-glycosylation motif of
      pseudorabies virus glycoprotein M result in expression of a nonglycosylated form
      of the protein.
AB  - Glycoprotein M (gM) constitutes one of the rare examples of a nonessential
      glycoprotein conserved throughout all herpesvirus subfamilies. Whereas gM in wild
      type pseudorabies virus (PrV) strains carries an N-glycan, gM of the attenuated
      strain Bartha is not glycosylated due to a point mutation in the N-glycosylation
      motif. Since PrV Bartha lacks glycoproteins E and I and carries a mutated gC, we
      analysed glycosylation of gM in isogenic PrV glycoprotein deletion mutants.
      Whereas gM was glycosylated normally in most mutants, two independent gC deletion
      mutants and a gI mutant expressed a nonglycosylated form of gM. DNA sequence
      analyses revealed the presence of point mutations in the N-glycosylation
      consensus motif. Surprisingly, mutations in strain Bartha, the two gC-deletion
      mutants and the gI mutant proved to be different, although all affected the N
      glycosylation motif. Thus, our data show that different, apparently independent
      point mutations cause expression of nonglycosylated gM.

PMID- 9568982
TI  - Human cytomegalovirus glycoprotein H/glycoprotein L complex modulates fusion-from
      without.
AB  - Glycoprotein H/glycoprotein L (gH/gL) complexes of herpesviruses are required for
      fusion of infecting virions with host cell membranes. In human cytomegalovirus
      (HCMV), neutralizing monoclonal antibodies (MAb) specific for gH inhibit the
      transfer of a fluorescent probe to the host cell from labelled virus particles.
      In similar fashion, in the present study, neutralizing gH-specific MAb inhibited
      HCMV-induced fusion-from-without in monolayers of both human embryonic
      fibroblasts and continuous astrocytoma cells (U373). No fusion was detected in
      cells co-infected with defective recombinant adenovirus vectors that elicited
      high-level expression of gH and gL, indicating that surface-expressed gH was not
      intrinsically fusogenic. However, when such cells were superinfected with HCMV
      that gave fusion-from-without, the resulting cell-to-cell fusion was considerably
      enhanced. Thus, under our experimental conditions, gH/gL on the cell surface
      functioned to increase membrane fusion once this was initiated by other
      components in the virus envelope.

PMID- 9568984
TI  - Intracellular and extracellular vaccinia virions enter cells by different
      mechanisms.
AB  - Vaccinia virus (VV) produces two antigenically distinct infectious virions,
      intracellular mature virus (IMV) and extracellular enveloped virus (EEV).
      Structurally, EEV consists of an IMV with an additional outer membrane containing
      proteins that are absent from IMV. EEV is important for virus dissemination both
      in vitro and in vivo. Studies of EEV entry have been hampered by having two
      infectious virions and by the rupture of the EEV outer membrane in the majority
      of EEV virions during their purification. To overcome these problems, we have
      developed a novel approach to study VV entry that is based on confocal microscopy
      and does not require EEV purification. This assay relies on immunofluorescent
      staining and detection of individual, intracellular, uncoated virus cores. By
      this method, we show that EEV entry, in contrast to IMV, is dependent on a low-pH
      pathway and that the IMV enwrapped inside the EEV exhibits a low-pH fusogenic
      activity. Together with neutralization data demonstrating that exposure to low pH
      disrupts the EEV outer membrane, this study strongly supports a model for EEV
      entry which consists of binding, endocytosis, low-pH-induced disruption of the
      EEV outer membrane and fusion of the exposed IMV with the endosomal membrane
      releasing the core into the cytosol. The roles of the EEV outer membrane in virus
      dissemination and virus entry are discussed in relation to this model.

PMID- 9568983
TI  - Evidence against a key role for transforming growth factor-beta1 in
      cytomegalovirus-induced bone marrow aplasia.
AB  - During immunodeficiency after sublethal haematoablative treatment,
      cytomegalovirus (CMV) infection interferes with haematopoietic reconstitution and
      can cause lethal bone marrow (BM) aplasia. The in vivo model of murine CMV
      infection has identified the BM stroma as the principal target site of CMV in the
      haematopoietic cord. The infected cell type is the reticular stromal cell which
      forms the stromal network and produces essential haemopoietins, such as stem-cell
      factor (SCF). The expression of SCF was found to be reduced in the infected
      stroma, but the stromal network was not disrupted and the number of infected
      stromal cells was too low to explain the functional deficiency. These facts call
      for a negatively regulating cytokine that is induced by the infection and that
      potentiates the direct effect of infection by down-regulating haemopoietins in
      uninfected bystander cells. Recent work has suggested that transforming growth
      factor (TGF)-beta1 might be the cytokine involved in CMV-induced BM aplasia. We
      show here that murine CMV indirectly induces the accumulation of mature TGF-beta1
      in uninfected renal tubular epithelial cells and TGF-beta1 transcription in BM
      stromal cells, whereas infected renal glomerular and interstitial cells,
      hepatocytes and BM stromal cells do not coexpress mature TGF-beta1. Antiviral CD8
      T-cell therapy prevented BM aplasia and also prevented the down-regulation of
      stromal SCF and interleukin-6 gene expression. Interestingly, however, the CD8 T
      cells did not preclude the up-regulation of mature TGF-beta1, but proved to be
      inducers of TGF-beta1 gene expression in BM stroma. These findings suggest that
      TGF-beta1 is not the mediator of BM aplasia.

PMID- 9568985
TI  - Beet yellows closterovirus HSP70-like protein mediates the cell-to-cell movement
      of a potexvirus transport-deficient mutant and a hordeivirus-based chimeric
      virus.
AB  - It has been suggested that the beet yellows closterovirus (BYV)-encoded p65
      protein, a homologue of HSP70 cell chaperones, plays a role as a virus movement
      protein (MP). To test this hypothesis, we used two types of complementation
      experiments with plant viruses containing the triple gene block (TGB) of MP
      genes. In one, the BYV p65 gene was cloned into a 35S promoter plasmid and
      introduced into Nicotiana benthamiana plants by microprojectile bombardment along
      with the 35S promoter-driven GUS gene-tagged cDNA of a transport-deficient
      potexvirus mutant. Transient expression of p65 complemented the mutant as
      visualized by the significant increase in the number of cells expressing the GUS
      reporter gene in the infection foci. In the other test, the p65 gene was inserted
      into the infectious cDNA of the hordeivirus RNA beta component to replace either
      the 58 kDa MP gene or the whole TGB. Inoculation of Chenopodium quinoa and
      Chenopodium amaranticolor plants with the T7 transcripts of the chimeric RNA
      beta, together with the hordeivirus RNA alpha and RNA gamma, caused symptomless
      infection in inoculated leaves detected by hybridization of the total leaf RNA
      with a specific cDNA probe. The ability of BYV p65 to substitute for the
      potexvirus or hordeivirus MPs provides direct evidence for its involvement in the
      cell-to-cell movement of closterovirus infection.

PMID- 9568986
TI  - Mutations in the HC-Pro gene of zucchini yellow mosaic potyvirus: effects on
      aphid transmission and binding to purified virions.
AB  - Transmission of zucchini yellow mosaic virus (ZYMV) by aphids was examined by
      introducing mutations within the highly conserved proline-threonine-lysine (PTK)
      motif of the helper component proteinase (HC-Pro) using a cDNA full-length clone.
      Replacement of proline by alanine (ATK) in the PTK motif abolished transmission
      almost completely both from plants and from membranes. Substitution of the basic
      lysine by glutamic acid (PTE) did not reduce the rate of transmission compared
      with the wild-type. Replacement of threonine by valine (PVK) or serine (PSK)
      resulted in a rate of transmission that was lower than that of the wild-type. The
      rate was lower for PSK than for PVK. Western blot comparison did not permit
      attribution of HC-Pro functionality in transmission to its level in the host. The
      HC-Pro of strains that effected transmission (with the wild-type PTK motif, and
      with the mutated PTE and PVK motifs) could also bind in vitro to virions of ZYMV.
      HC-Pro with a PSK motif, which was less effective in assisting transmission,
      could bind only weakly to virions, while HC-Pro of the almost non-transmissible
      strains (with PAK and ATK motifs) did not bind at all. Interestingly, positive
      binding was recorded for transmission-defective ZYMV-Ct, which has a PTK motif
      but has glutamic acid instead of lysine in the lysine-leucine-serine-cysteine
      (KLSC) motif. These findings support the 'bridge hypothesis', and confirm the
      binding of the HC-Pro to the virion. The possible role of the PTK and KLSC motifs
      in binding to the virus and to the mouthparts of the aphid is discussed.

PMID- 9568987
TI  - Specific sequence changes in the 5'-terminal region of the genome of satellite
      tobacco mosaic virus are required for adaptation to tobacco mosaic virus.
AB  - The genome of satellite tobacco mosaic virus (STMV) adapted to tobacco mosaic
      virus (TMV), tomato mosaic virus or green tomato atypical mosaic virus
      consistently had two single base deletions at positions 1 and 61, corresponding
      to bases A and G, respectively, as compared to the type-strain genome which is
      naturally adapted to tobacco mild green mosaic virus (TMGMV). Transcript RNAs
      (STMV(TMV)) from clone pSTMV(TMV) which captured the deletions at positions 1 and
      61 were infectious when co-inoculated to tobacco plants with either TMV or TMGMV
      at infection frequencies of > 90%. Two new STMV variants were created to
      investigate whether both deletions were essential for adaptation to TMV. These
      were STMV(TMGMV) deltaA1, which had the A at position 1 (A1) deleted, and
      STMV(TMGMV) deltaG61, which lacked G61. STMV(TMGMV) deltaA1 was infectious (75%
      frequency) in the presence of either TMV or TMGMV. Virion RNA of STMV(TMGMV)
      deltaA1 lost G61 after one infection cycle with TMV. This deletion did not occur
      in co-infections with TMGMV. STMV(TMGMV) deltaG61, like the clone STMV(TMGMV),
      was infectious (100% frequency) with TMGMV but TMV did not support this clone.
      When Nicotiana benthamiana protoplasts were transfected with STMV(TMGMV),
      STMV(TMGMV) deltaA1 or STMV(TMV), STMV replicated when TMGMV was the helper
      virus. STMV(TMV) and STMV(TMGMV) deltaA1 replicated in the presence of helper
      TMV, but STMV(TMGMV) did not, the same result as in whole plants. The deletion of
      A1 is thus essential for initial STMV adaptation to TMV and the eventual deletion
      of G61 is a predicted additional change.

PMID- 9568988
TI  - Four DNA-A variants among Pakistani isolates of cotton leaf curl virus and their
      affinities to DNA-A of geminivirus isolates from okra.
AB  - Complete DNA-A sequences of nine Pakistani geminivirus isolates from leaf curl
      affected cotton (CLCuV-PK) or from okra, and the partial sequences of several
      additional isolates were determined. Sequences of isolates from cotton were of
      four types. Isolates from leaf curl-affected okra had virtually the same
      sequences as those from cotton. Isolates from yellow vein mosaic-affected okra
      were of two types (OYVMV types 201 and 301), both distinct from but closely
      related to the virus isolates from cotton. Of these six types, two types of CLCuV
      PK are the most closely related but another (CLCuV-PK type 72b) is the most
      distinct. Of the encoded proteins, coat protein (CP) is the most strongly
      conserved (92-100% amino acid sequence identity), and AC4 protein the most
      variable (41-87%). The 5' and 3' halves of the intergenic region of some isolates
      had different affinities and occurred in seven combinations, suggesting that
      recombination had occurred and that the origin of replication was a favoured
      recombination site. Similarly, the first 1520 nt of CLCuV-PK type 804a DNA
      resembled those of OYVMV type 301 DNA but the remaining 1224 nt were very
      different. The AC1 (Rep) gene and 5' part of the intergenic region of CLCuV-PK
      type 72b closely resembled those of OYVMV type 301, whereas the rest of the
      sequence did not. The cotton leaf curl epidemic in Pakistan is caused by several
      distinct variants, with recombination events involving OYVMV and other
      unspecified geminiviruses having probably been involved in their evolution.

PMID- 9568989
TI  - Tubules containing virions are present in plant tissues infected with Commelina
      yellow mottle badnavirus.
AB  - Tubular structures containing bacilliform virions were observed in cell-free
      extracts of Commelina diffusa infected with Commelina yellow mottle badnavirus
      (CoYMV). The exterior of the tubule reacted with antibodies to CoYMV movement
      protein, but not with antibodies to virus coat protein. Similar tubular
      structures containing bacilliform particles were also observed in ultrathin
      sections of CoYMV-infected C. diffusa. These tubular structures traversed the
      cell wall at points where this was thickened or protruded. No similar structures
      were observed in healthy C. diffusa. These observations support the hypothesis
      that the virion-containing tubular structures observed in cell-free extracts are
      the same as those observed in situ, that these structures are composed, at least
      in part, of virus movement protein, and that they play a role in the cell-to-cell
      trafficking of virions of CoYMV.

PMID- 9568990
TI  - Two key mutations in the host-range specificity domain of the p143 gene of
      Autographa californica nucleopolyhedrovirus are required to kill Bombyx mori
      larvae.
AB  - Autographa californica nucleopolyhedrovirus (AcMNPV) does not replicate in Bombyx
      mori cells (Bm5, BmN). We have shown previously that when a short DNA sequence
      within AcMNPV ORF95, which encodes the viral helicase P143, is replaced with the
      colinear region of B. mori nucleopolyhedrovirus (BmNPV), AcMNPV gains the ability
      to replicate in Bm5 cells. To determine the mutational events in the p143 gene
      required to allow AcMNPV replication in B. mori cells, AcMNPV recombinants
      produced in Sf9 cells were screened in vivo in B. mori larvae, which are more
      permissive to baculovirus infection than B. mori cell lines. Eight combinations
      of mutations were tested and characterization of viral DNA extracted from dead
      larvae showed that amino acid changes at position 564 and 577 are required to
      kill B. mori larvae.

PMID- 9568991
TI  - Synthetic peptide vaccines yield monoclonal antibodies to cellular and
      pathological prion proteins of ruminants.
AB  - Transmissible spongiform encephalopathies are closely linked to the accumulation
      of a pathological isoform of a host-encoded prion protein (PrP(C)), designated
      PrP(Sc). In an attempt to generate mono- and polyclonal antibodies to ruminant
      PrP, 32 mice were vaccinated with peptide vaccines which were synthesized
      according to the amino acid sequence of ovine PrP. By this approach five PrP
      reactive polyclonal antisera directed against four different domains of the
      protein were stimulated. Splenocytes of mice which had developed PrP-reactive
      antibodies were used for the generation of monoclonal antibodies (MAbs). Obtained
      PrP-specific MAbs were directed to three different domains of ruminant PrP which
      differed from the three previously described major MAb binding sites in rodent
      PrP. MAbs exhibited reactivity with non-denatured ruminant PrP(C) in ELISA and
      immunoprecipitation and with denatured ovine and bovine PrP(Sc) in immunoblot.
      Cross-reactivity was observed with PrP(C) of nine other mammalian species and
      with pathological PrP preferably of ruminants and weakly with that of hamster and
      mouse. The generated MAbs will be useful tools for the development of diagnostic
      tests for BSE and scrapie as well as for pathogenesis studies of these diseases.

PMID- 9568992
TI  - Hydatidosis -- a zoonosis of unrecognised increasing importance?

PMID- 9568993
TI  - The 18th C.L. Oakley Lecture. Pathogenicity of enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) remain an important world-wide cause of
      diarrhoeal disease and mortality of infants and young children. Research
      programmes around the world have, in recent times, made enormous strides towards
      a better understanding of EPEC pathogenesis, yielding unique insights into the
      molecular intercourse between host and pathogen. Recombinant DNA and cell biology
      techniques have provided powerful tools, giving the first intriguing glimpses of
      a wealth of bacterial products mediating complex host:pathogen interactions
      involving the subversion of normal host signalling processes. Much has been
      discovered since 1945, when E. coli was first implicated as a cause of diarrhoea.
      However, many questions remain unanswered and many more remain unasked. Much
      remains to be discovered, especially in the area of molecular interactions
      between host and pathogen and how they relate to the manifestation of disease in
      the patient.

PMID- 9568994
TI  - Effect of immunisation with Pseudomonas aeruginosa on gut-derived sepsis in mice.
AB  - The protective efficacy of immunisation with heat-killed Pseudomonas aeruginosa
      on murine gut-derived sepsis was evaluated. Mice were immunised intraperitoneally
      six times with heat-killed bacteria. This induced mean (SEM) serum IgG and IgM
      antibodies of 1792 (374.7) and 37.3 (8.9) ELISA units, respectively. Specific
      pathogen-free mice given P. aeruginosa strain D4 orally died of bacteraemia after
      administration of cyclophosphamide. Immunisation with heat-killed bacteria
      significantly increased the survival rate compared with that of control mice
      immunised with bovine serum albumin. Macroscopic observation revealed marked
      production of liver abscesses in mice immunised with bovine serum albumin but not
      in those immunised with heat-killed bacteria. Only low titres of antibody against
      the exoenzymes alkaline protease, elastase and exotoxin A were observed, and no
      significant difference between antibody titres to boiled and unboiled suspensions
      of sonicated P. aeruginosa was detected. This suggests that the main protective
      antibodies might be those specific to the heat stable antigen
      (lipopolysaccharide). Immunisation with heat-killed bacteria provided complete
      protection against death from gut-derived P. aeruginosa sepsis.

PMID- 9568995
TI  - Efficacies of alkaline protease, elastase and exotoxin A toxoid vaccines against
      gut-derived Pseudomonas aeruginosa sepsis in mice.
AB  - The protective efficacies of vaccines prepared from Pseudomonas aeruginosa
      alkaline protease, elastase and exotoxin A toxoids against gut-derived P.
      aeruginosa sepsis in mice were evaluated. Specific pathogen-free mice given P.
      aeruginosa strain D4 orally followed by cyclophosphamide (to promote
      translocation across the gut wall) died of bacteraemia. Mice immunised with one
      of the three individual toxoid vaccines were not significantly protected when
      compared to control mice immunised with bovine serum albumin. Combined
      immunisation with alkaline protease and elastase toxoids likewise showed no
      significant protective activity. However, combined immunisation with alkaline
      protease and exotoxin A toxoids significantly increased the survival rate, which
      reached 60% (compared with a 7.1% survival rate in the control group). These
      results show that alkaline protease and exotoxin A play important roles as
      pathogenic factors in gut-derived sepsis and that a combination of the two
      exoenzyme toxoids represents a logical candidate for vaccination against P.
      aeruginosa sepsis.

PMID- 9568997
TI  - Preparation of diagnostic polyclonal and monoclonal antibodies against outer
      envelope proteins of Serpulina pilosicoli.
AB  - The purpose of this study was to prepare specific sera for use in the rapid
      detection and identification of the intestinal spirochaete Serpulina pilosicoli.
      In Western blot analysis, with pig antiserum which was raised against whole cells
      of S. pilosicoli and absorbed with outer envelope protein extracts from S.
      hyodysenteriae and S. innocens, a prominent protein with Mr of c. 72 kDa was
      consistently identified in outer envelope preparations of S. pilosicoli strains.
      Immunogold labelling demonstrated that this was located on the outer surface of
      intact S. pilosicoli cells. Two monoclonal antibodies (MAbs), designated C12 and
      M96, were raised against the protein. Although C12 reacted with a protein band of
      c. 72 kDa, this was also present in preparations from strains of other Serpulina
      spp. examined. MAb M96 reacted with an 80-kDa protein which was present only in
      preparations made from strains of S. pilosicoli. This was used in Western blot
      analysis and in an immunodot-blot assay with outer envelope extracts to
      specifically identify S. pilosicoli strains isolated from man, pigs, dogs and
      poultry. An indirect immunofluorescence test with MAb M96 also was used to detect
      and identify whole S. pilosicoli cells. Therefore, both the cross-absorbed
      antiserum and MAb M96 are potentially useful reagents for the detection and
      identification of S. pilosicoli.

PMID- 9568996
TI  - Molecular analysis of the promoter region of the Clostridium difficile toxin B
      gene that is functional in Escherichia coli.
AB  - Clostridium difficile is a human pathogen that produces two types of toxins, A
      and B, that cause a potentially lethal gastrointestinal syndrome termed
      pseudomembranous colitis. Virtually nothing is known about the mechanism of
      regulation of toxin production in this organism, and cis-regulatory regions of
      neither toxin have yet been identified, thus prompting this investigation. A
      motif homologous with the Shine-Dalgarno sequence of Escherichia coli occurs
      upstream from the putative initiation codon of toxin B, making this region also a
      candidate to contain a promoter. Therefore, a subgenomic DNA library of C.
      difficile in a plasmid vector was first constructed encompassing the 5'-end of
      the toxin B gene. A 450-bp DNA fragment was excised from the subgenomic DNA
      library clone and subcloned into a promoter-probe plasmid vector that contains
      two divergently oriented, promoterless genes to assay for promoter function. This
      subcloned DNA fragment directed the expression of alkaline phosphatase, a
      reporter gene product of the promoterless vector, thus indicating the presence of
      a functional promoter. To locate the promoter more precisely, a series of nested
      deletions of the toxin B promoter subclone was constructed with exonuclease III.
      The promoter that facilitates expression of the toxin B gene in E. coli was
      localised, based on alkaline phosphatase activity. The transcriptional initiation
      site of toxin B mRNA in E. coli was mapped by primer extension analysis,
      suggesting two closely associated tandem start sites directed by two similarly
      spaced promoters within this localised region.

PMID- 9568998
TI  - Evaluation of clinical usefulness of the microplate agglutination test for
      serological diagnosis of legionella pneumonia.
AB  - Recently, a microplate agglutination test (MPAT) was established for the
      serological diagnosis of legionella pneumonia. To evaluate its usefulness, this
      study examined antibody titres in 121 serum samples serially obtained from 40
      patients with pneumonia, including 17 cases of confirmed legionella pneumonia.
      Six of the 17 proven cases became serologically positive within 4 weeks of the
      onset of pneumonia as assayed by MPAT (cut-off value: four-fold rise to > or =
      128 in paired sera or > or = 256 in a single serum specimen), whereas the
      remaining 11 cases were serologically negative despite serial examination. Four
      proven cases who were treated with corticosteroids in the acute phase had
      antibody titres <8 during the first 4 weeks of infection, after which one case
      showed an elevation in antibody titre for the first time, 13 weeks after the
      onset of disease. In contrast, all non-proven cases had antibody titres of < or =
      64, and only one case developed a four-fold or greater rise in titre. These
      results indicate that MPAT is a useful method for the laboratory diagnosis of
      suspected legionella pneumonia, although several false-negative cases were
      observed. This suggests that the previously established MPAT criteria may require
      modification, possibly to slightly lower values. These data also indicate that
      serial examination over the first month of infection may be necessary for
      serodiagnosis of legionella pneumonia, especially in patients treated with
      corticosteroids.

PMID- 9569000
TI  - Development of a multiplex-PCR for direct detection of the genes for enterotoxin
      B and C, and toxic shock syndrome toxin-1 in Staphylococcus aureus isolates.
AB  - As well as conventional methods such as immunodiffusion, ELISA, or agglutination
      for the detection of toxin production in Staphylococcus aureus, amplification
      techniques like PCR allow a very sensitive and specific identification of the
      genes responsible for enterotoxin B and C, and TSST-1 production. These toxins
      might be a cause of the toxic shock syndrome (TSS). For that reason an easy and
      quick test system for determining the toxin production pattern of S. aureus
      isolates is desirable so that strains suspected to be toxin producers may be
      identified much faster and easier. In the present investigation, a new multiplex
      PCR method was used that allowed single bacterial colonies grown on agar plates
      to be used directly in the PCR assay without preceding preparation. This
      procedure generated information concerning the presence of seb, sec-1 and tst
      genes within 4 h in a single test. To analyse the sensitivity and the specificity
      of this procedure, 100 methicillin-resistant S. aureus (MRSA), 50 coagulase
      negative staphylococci and 50 other eubacterial isolates were tested initially
      with sets of single primer pairs followed by a combined multiplex-PCR. Results of
      this amplification technique were compared to a conventional and widely used
      method for toxin detection, reversed passive latex agglutination (RPLA). With the
      RPLA assay results as the basis, sensitivity and specificity of the seb and tst
      primer sets were 100%, whereas sensitivity and specificity of the sec-1 primer
      set were 100% and 82%, respectively. With the sec-1 primer set, two isolates were
      identified as carrying the corresponding toxin gene although the RPLA test did
      not show any detectable toxin. The multiplex-PCR rapidly generated reliable
      information concerning the toxin-producing capacity of staphylococcal strains and
      could be easily integrated into a multiplex procedure described previously. The
      latter enabled the identification of specific PCR products for eubacteria and
      staphylococci as well as the detection of the coa and mecA genes.

PMID- 9568999
TI  - Detection of Pneumocystis carinii among children with chronic respiratory
      disorders in the absence of HIV infection and immunodeficiency.
AB  - A nested polymerase chain reaction (PCR) assay was investigated for detection of
      Pneumocystis carinii in 96 respiratory tract specimens from 82 children, of whom
      28 were immunocompetent but with chronic lung disorders (CLD), eight had AIDS and
      P. carinii pneumonia (PCP), 16 had AIDS but no respiratory symptoms, and 30 were
      healthy immunocompetent children. Gomori methenamine silver stain (GMS) and
      indirect immunofluorescence assay (IFA) were performed in parallel. Of 36
      specimens from children with CLD, 12 were P. carinii PCR-positive compared to 10
      positive by GMS-IFA. Of eight specimens from children with AIDS and PCP, seven
      were P. carinii-positive by PCR and six by GMS-IFA, and of 22 specimens from HIV
      positive children without respiratory symptoms, two were positive by PCR and none
      by GMS-IFA. P. carinii DNA was also detected by PCR in blood samples from four
      children with P. carinii-positive nasopharyngeal aspirates. Specimens from
      healthy children were negative for P. carinii by both PCR and GMS-IFA. Of the
      seven children with CLD, who were P. carinii-positive, two had clinical and
      microbiological improvement with co-trimoxazole treatment, two improved initially
      but relapsed, and one had P. carinii cysts persistently in follow-up specimens
      despite co-trimoxazole treatment. These results suggest an association between P.
      carinii and exacerbations of CLD in childhood, in the absence of HIV infection or
      other immunodeficiency syndromes.

PMID- 9569001
TI  - Typing of methicillin-resistant Staphylococcus aureus isolates from Dusseldorf by
      six genotypic methods.
AB  - Nosocomial infections caused by methicillin-resistant Staphylococcus aureus
      (MRSA) represent an increasing problem in hospitals. Quick and reliable typing
      methods are required to obtain information about the relatedness of MRSA isolates
      and to allow faster implementation of appropriate infection control measures.
      This investigation describes the distribution of MRSA isolates from 11 hospitals
      in the Dusseldorf region of Germany, and the ability of six different genotypic
      typing techniques -- pulsed-field gel electrophoresis (PFGE), random
      amplification of polymorphic DNA (RAPD), 16S-23S rDNA spacer amplification,
      protein A-gene PCR, PCR characterisation of the hypervariable region (HVR)
      adjacent to mecA, and coagulase gene-PCR -- to detect different unrelated types.
      Of 7814 S. aureus isolates tested, 489 (6.3%) were MRSA, of which 183 were
      selected for subsequent molecular analyses on the basis of being the first MRSA
      isolated from colonised or infected patients. Larger hospitals had a higher
      incidence of MRSA and a greater variability in genotypes than smaller hospitals.
      All methods confirmed the presence of two main clonal types. The ability of
      techniques to detect different unrelated types was found to be as follows: PFGE,
      28 types; 16S-23S rDNA spacer-amplification, 10 types; RAPD, nine types; protein
      A-gene PCR, five types; HVR-PCR, five types; and coa gene-PCR, two types.
      Combination of PFGE and one other PCR-based method (spacer-amplification, RAPD or
      protein-A gene PCR) provided the best resolution of types and allowed the
      identification of subtypes. Similar molecular types were identified with
      international MRSA isolates. Although PCR-based techniques have the advantage of
      rapid performance and easy handling, their discriminatory capacity is inferior
      compared to the more labour intensive PFGE.

PMID- 9569002
TI  - Subtyping of Campylobacter jejuni Penner heat-stable (HS) serotype 11 isolates
      from human infections.
AB  - High resolution molecular subtyping was applied to Campylobacter jejuni Penner
      heat-stable (HS) 11 isolates from human infections and other sources. Strains
      were genotyped by restriction fragment length polymorphism analysis involving PCR
      based flagellin gene (flaA) profiling with HinfI and DdeI, and pulsed-field gel
      electrophoretic (PFGE) profiling with SmaI and KpnI. Fla-genes of the strains
      were highly conserved as most (95%) had the same fla-profile. PFGE analysis of
      SmaI digests was more discriminatory with 15 profile subtypes identified,
      although 36% of isolates had a common profile. The study showed that strains of
      C. jejuni HS11, unlike those of HS1 and the HS4 complex, were relatively
      homogeneous at the genomic level and that high resolution molecular techniques
      were essential for detailed epidemiological subtyping.

PMID- 9569003
TI  - Effect of granulocyte-macrophage colony-stimulating factor on candidacidal
      activity of neutrophils, monocytes or monocyte-derived macrophages and synergy
      with fluconazole.
AB  - The effect of in-vitro granulocyte-macrophage colony-stimulating factor (GM-CSF)
      treatment of neutrophils, monocytes or monocyte-derived macrophages (MDM) on
      candidacidal activity was tested. Synergy of effector cells with fluconazole
      (FCZ) for enhanced killing was also investigated. Incubation of neutrophils with
      GM-CSF 0.67 microg/L plus Candida albicans Sh27 for 24 h significantly increased
      candidacidal activity (36% versus 74%). Synergy with FCZ for killing was also
      significantly increased from 93% to 97% when neutrophils were incubated with GM
      CSF. Monocytes cultured with GM-CSF and C. albicans for 24 h had significantly
      increased fungistatic activity compared to controls and synergy with FCZ for
      killing was significantly enhanced from 40% to 59%. Monocytes cultured for 3 days
      with GM-CSF had increased fungistatic activity compared to control MDM and showed
      synergy with FCZ for significantly enhanced killing (46%) compared to control MDM
      (12%).

PMID- 9569004
TI  - Haemolysin from Mycobacterium avium complex isolates from AIDS patients.
AB  - Cell-bound haemolytic activity was observed in isolates of Mycobacterium avium
      complex (MAC) from AIDS patients. M. avium type strains showed negligible
      activity. None of the culture supernates exhibited any haemolytic activity.
      Zwitterionic detergent 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1
      propanesulphonate (CHAPS) was used to extract haemolysin from ethanol-treated M.
      avium complex strain 101 (MAC101) cells. Haemolysin was isolated from CHAPS
      extract (CE) by metal affinity chromatography and identified as a 32-kDa protein
      by polyclonal antibodies raised against M. tuberculosis haemolysin. Treatment of
      CE with trypsin resulted in reduction of haemolytic activity, whereas heating at
      100 degrees C for 10 min did not affect its activity. A similar 32-kDa haemolysin
      was extracted from cells of M. avium K128 which was isolated from a monkey
      infected with simian immunodeficiency virus (SIV). The haemolysin produced by M.
      avium strains isolated from AIDS patients may be associated with the pathogenesis
      of M. avium infection.

PMID- 9569005
TI  - Modulation of hormone-dependent glucocorticoid receptor function using a
      tetracycline-regulated expression system.
AB  - The glucocorticoid receptor (GR) is a ligand-dependent transcription factor
      capable of stimulating and inhibiting the expression of target genes. To better
      understand the biological action of glucocorticoids and the function of GR, we
      have utilized the tetracycline (Tc)-regulated mammalian expression system to
      develop a novel cell line, E8.2/GR3, derived from GR null mouse L929 fibroblasts,
      that exhibits conditional expression of rat GR. The intracellular concentration
      of rGR in E8.2/GR3 cells--from undetectable levels to levels more than 10-fold
      greater than that observed in wild-type L929 cells--could be manipulated by
      varying the Tc concentration in the culture media. Similarly, dexamethasone (DEX)
      dependent transactivation of the mouse mammary tumor virus long terminal repeat
      and transrepression of the cadmium-induced activity of the mouse heme oxygenase-1
      gene enhancer, SX2, were strictly dependent on the presence of rGR, and the
      levels of these activities could be modulated by Tc. Similar levels of Tc, and
      thus rGR, were required for half-maximal transactivation and transrepression
      whereas a 6-fold lower concentration of DEX was required for half-maximal
      transrepression than for transactivation. RU486 inhibited both DEX-dependent
      transactivation and transrepression. DEX decreased the steady-state level of rGR
      mRNA and protein in a Tc dependent manner. DEX also induced morphological changes
      in E8.2/GR3 cells that were dependent on rGR as no alterations were observed in
      the presence of Tc. These cells provide a powerful system for examining the
      various activities of GR, particularly as a function of different intracellular
      receptor concentrations.

PMID- 9569006
TI  - Estrogen-induced genes in the uterus of ovariectomized rats and their regulation
      by droloxifene and tamoxifen.
AB  - The identification and characterization of estrogen regulated genes in
      reproductive tissues is an important step in understanding estrogen's mechanism
      of action in sexual development and neoplasia. It is also important, given the
      clinical interest, to evaluate the molecular effects of estrogen
      agonists/antagonists such as tamoxifen and droloxifene in reproductive tissues.
      In this report, our goal was to identify estrogen regulated genes in the uterus
      and to compare the regulation by estrogen and tamoxifen with that of droloxifene.
      A subtractive cDNA library strategy was developed to identify estrogen-regulated
      genes in the uteri of ovariectomized rats 4 h after treatment with 17-alpha
      ethynyl estradiol (30 microg/kg). The mRNAs encoding 8 genes were confirmed by
      Northern blot analysis to be induced at early times following estrogen
      administration. Calcium binding protein 9 kDa and complement protein 3 are well
      characterized estrogen regulated genes that were identified in the library and
      served as markers for estrogen action. In addition, mRNAs encoding the
      interleukin 4 receptor, heat-shock protein 70 kDa, metallothionein, tumor
      necrosis factor regulated gene 6, inositol-1-monophosphate synthase, and cyr-61
      were induced in the uterus by estrogen. The identified mRNAs were then examined
      for regulation by droloxifene (1 and 10 mg/kg, p.o.) and tamoxifen (10 mg/kg,
      p.o.). Both droloxifene and tamoxifen induced mRNA levels for all of these genes.
      However, clear quantitative and temporal differences were observed when comparing
      estrogen versus droloxifene versus tamoxifen. For example, estrogen induced IL4
      receptor mRNA to a greater degree than did tamoxifen or droloxifene. Conversely,
      tamoxifen resulted in a much greater induction of cyr61 than did either estrogen
      or droloxifene. Droloxifene at 1 mg/kg, an efficacious dose for prevention of
      bone loss in this model, did not or only slightly induced the mRNA for all of the
      genes examined with the exception of cyr61. In conclusion, the modified
      subtractive library method used in this study proved to be efficient in the
      identification of estrogen-regulated genes in the uterus. The identities of the
      regulated genes were consistent with the concept that estrogen functions to prime
      uterine tissue for increased responsivity to extracellular signals such as growth
      factors and cytokines. Elucidating the physiological role of these newly
      identified estrogen responsive genes and the mechanisms responsible for the
      different responses to droloxifene versus estrogen and tamoxifen may be important
      in enhancing our understanding of tissue selective estrogen agonists/antagonists.

PMID- 9569007
TI  - Expression and estrogen regulation of the HEM45 MRNA in human tumor lines and in
      the rat uterus.
AB  - A human estrogen regulated transcript, HEM45, was characterized that encodes a
      novel protein of 181 amino-acid residues (Mr 20300). It was identified using
      differential-display-PCR and mRNA from a human cervical cancer cell line (UP1)
      stably transfected with an estrogen receptor (ER) expression construct. The HEM45
      protein has similarity to the bracket fungus protein FRT1 that can cause fruiting
      body production and to a Xenopus product, XPMC2, that affects cell-cycle control.
      These similarities suggest that HEM45 will have a role in mediating estrogen
      control of cellular proliferation and differentiation. HEM45 mRNA was widely
      expressed at low levels in cell lines and was up regulated by E2 in ER-positive
      breast cancer lines. The in vivo regulation of HEM45 was confirmed by
      demonstrating estrogen stimulation of the rat HEM45 homolog in the rat uterus.
      The levels of the rat uterine HEM45 sequence were elevated by estrogen 3 to 15 h
      after treatment. The maximal response, at six hours, was greater than eight-fold.
      The uterine HEM45 response was distinct from that reported for 'early-response'
      genes as the increase in HEM45 mRNA levels occurred later but could be induced by
      lower levels of hormone. HEM45 mRNA expression in cultured cells was increased by
      estrogen in the presence of cycloheximide, indicating direct ER-regulation of
      HEM45.

PMID- 9569008
TI  - Decreased apparent affinity of corticosterone for colonic crypt glucocorticoid
      receptors is dependent on the cellular milieu and is distinct from corticosterone
      metabolism.
AB  - [3H]Steroid binding in intact colonic crypt cells and cytosol was compared to
      determine if 11beta hydroxysteroid dehydrogenase (11betaHSD) activity modulates
      access of corticosterone (B) to both glucocorticoid receptors (GR) and
      mineralocorticoid receptors (MR). Cytosol from non-adrenalectomized rat colonic
      crypt cells showed no 11betaHSD activity, and B bound with high affinity to both
      MR (Kd=0.47+/-0.03 nM; Bmax=177+/-34 fmol/mg protein) and GR (Kd=4.5+/-0.3 nM;
      Bmax=279+/-40 fmol/mg protein). In contrast, intact colonic crypt cells incubated
      with 25-30 nM [3H]B for 90 min converted 62% of B to 11-dehydrocorticosterone,
      with little binding to MR (14+/-3 fmol/mg protein) and GR (22+/-5 fmol/mg
      protein). When 11betaHSD activity was inhibited with carbenoxolone, and the same
      concentration of [3H]B used, binding of [3H]B to MR increased 10-fold to 122+/-12
      fmol/mg protein, not significantly different from MR levels in colonic crypt
      cytosol. In contrast, [3H]B binding to GR in intact cells increased only 1.6-fold
      to 36+/-9 fmol/mg protein, significantly less than to GR in cytosol (212+/-24
      fmol/mg protein). Scatchard analysis showed both lower levels of GR and an
      apparently lower affinity for [3H]B in colonic crypt cells (Kd=31+/-3 nM;
      Bmax=130+/-21 fmol/mg protein) compared with cytosol (Kd=4.5+/-0.3 nM; Bmax=279+/
      40 fmol/mg protein. [3H]Dexamethasone similarly showed an apparently lower
      affinity and capacity for GR (Kd=8.8+/-1.3 nM; Bmax=232+/-32 fmol/mg protein) in
      intact cells compared with cytosol (two separate determinations, Kd=2.6 and 2.9
      nM; Bmax=369 and 300 fmol/mg protein). In contrast, [3H]aldosterone displayed
      similar affinity and capacity for MR in both intact cells (Kd=2.0 nM; Bmax=121
      fmol/mg protein) and cytosol (Kd=1.5 and 1.4nM; Bmax=115 and 93 fmol/mg protein).
      These findings demonstrate not only that 11betaHSD modulates binding to both MR
      and GR in colonic crypt cells, but also that an additional mechanism(s) operating
      in whole cells but not in cytosol selectively reduces the affinity and capacity
      of colonic GR for both natural and synthetic ligands.

PMID- 9569009
TI  - Effect of fibroblastic growth factors (FGF) on steroid UDP
      glucuronosyltransferase expression and activity in the LNCaP cell line.
AB  - It is now widely accepted that factors other than androgens are crucial in the
      normal and abnormal growth of the prostate. In addition to hormones, many
      polypeptide growth factors, including the fibroblast growth factor family (FGF),
      can act as potent mitogens on cell proliferation. The FGF family of growth
      factors are essential factors for both normal and abnormal proliferation of
      prostate cells. To study the effect of FGFs on steroid glucuronidation, we used
      the human prostate cancer LNCaP cell line which is known to be stimulated by FGF
      resulting in increased cell proliferation. LNCaP cells express steroid
      metabolizing enzymes including uridine diphosphoglucuronosyltransferases (UGTs).
      In addition, LNCaP cells treated with dihydrotestosterone (DHT) and epidermal
      growth factor (EGF) express differential levels of the human UGT2B15 and UGT2B17
      transcripts. In the present study, we examined the possible interaction between
      FGF and steroid UGT enzymes. Results show a dose dependent inhibition of DHT
      glucuronide (DHT-G) formation following treatment (6 days) with acidic FGF (aFGF)
      and basic FGF (bFGF). When cells were treated with 10 ng/ ml of FGFs, we observed
      33 and 51% inhibition of glucuronidation activity using aFGF and bFGF
      respectively. Ribonuclease protection analyses revealed a 2 and 3 fold increase
      of UGT2B15 mRNA expression following treatment with aFGF (50 ng/ml) and bFGF (10
      ng/ml) respectively. However, a slight decrease in UGT2B17 transcripts was
      observed, demonstrating a differential regulation. Since a reduction in the
      glucuronidation of DHT or its 5alpha-reduced metabolites may contribute to an
      increase in intraprostatic androgen levels, down-regulation of UGTs by growth
      factors such as FGFs may increase the proliferation of androgen-dependent tumors.

PMID- 9569010
TI  - The two native estrogen receptor forms of 8S and 4S present in cytosol from human
      uterine tissues display opposite reactivities with the antiestrogen tamoxifen
      aziridine and the estrogen responsive element.
AB  - We have investigated the capability of the different native ER forms, present in
      cytosols from human uterine tissues, of reacting with the antiestrogen
      [3H]Tamoxifen aziridine ([3H]TA) and with the Estrogen Responsive Element (ERE).
      Cytosols from uterine leiomyoma (myoma) prepared in buffer containing 40 mM
      molybdate and protease inhibitors, labelled with [3H]estradiol and analyzed in
      low-salt sucrose gradient showed 8S and 4S ER forms. The same cytosols labelled
      with [3H]TA only showed a 4S ER form, whereas the ERE only reacted with fractions
      from the 8S peak. The band of ERE reaction in the EMSA assay showed a lower
      relative mobility than the band labelled with [3H]TA, but both bands contained
      immunoreactive ER of 65 kDa. Electrophoretic mobility of the [3H]TA-labelled band
      in that system was not affected by cytosol treatment with cross-linkers or SDS,
      which suggests that it is a monomeric protein. The [3H]TA-binding 4S ER form was
      found in all studied myoma samples, as well as in human endometrium or
      myometrium, but not in rat tissues. These results suggest that the 8S and 4S ER
      form were already present before cytosol from human uterine tissues comes into
      contact with the molybdate buffer. They both contain the same ER molecule of 65
      kDa, either in the free form or as an oligomer. Only the ER dimers, which have
      been described both in the cytosolic 8S form and in the nuclear 4-5S form, react
      with the ERE. [3H]TA only binds to the 4S ER monomer probably because its binding
      site is concealed in the 8S form under these experimental conditions. The
      opposite reactivity of the 8S and 4S ER forms with [3H]TA and the ERE support the
      hypothesis that they may constitute separate entities with a different
      physiological role.

PMID- 9569011
TI  - Mechanisms in progestin antagonism of pituitary tumorigenesis.
AB  - Chronic exposure of F344 rats to diethylstilbestrol (DES) induces pituitary
      tumors (DES-T) composed of proliferating lactotrophs. Presently, we studied the
      effect of progestins on parameters related to tumor growth and function, due to
      previous evidences of progesterone antagonism of pituitary tumorigenesis acting
      at pituitary and hypothalamic levels [Piroli, G., Grillo, C., Ferrini, M., Lux
      Lantos, V. and De Nicola, A. F., Antagonism by progesterone of diethylstilbestrol
      induced pituitary tumorigenesis in Fischer 344 rats: Effects on sex steroid
      receptors and tyrosine hydroxylase mRNA, Neuroendocrinology, 1996, 63, 530-539].
      In search of a quantitatively more important effect, animals bearing DES-T were
      treated with synthetic progestins. Competition assays using DES-T as source of
      progestin receptors indicated that levonorgestrel (LNG), gestodene and R5020
      showed higher affinities (IC50 1-2 nM) than progesterone, norethisterone and
      medroxyprogesterone (IC50 10-25 nM). Treatment with LNG reduced DES-T weight by
      45%, and serum PRL by one half. Small (monomeric) and big (polymeric) PRL
      increased 5- and 2.5-fold, respectively, in DES-T in comparison with pituitaries
      of ovariectomized (OVX) rats. However, LNG produced no changes indicating that
      synthesis and storage of PRL was conserved in rats receiving both hormonal
      treatments. DES induced a 15-fold increase in cell proliferation, measured as
      bromodeoxyuridine incorporation into cell nuclei, in comparison to OVX rats,
      while LNG treatment of DES-T bearing rats reduced this index by 72%. Electron
      microscopic images showed that LNG markedly reduced hypertrophy and hyperplasia
      of lactotropes, increasing the proportions of degenerating cells and cells of
      high electronic density with alterations of cytoplasmic organelles. However,
      histopathological signs of apoptosis were absent. Therefore, reduced cell
      proliferation and non-apoptotic cell death are part of the mechanisms employed by
      progestins to antagonize tumorigenesis at the pituitary level. The results may
      open a new therapeutic strategy for treatment of PRL secreting adenoma in humans.

PMID- 9569013
TI  - A 6beta-(thiaheptanamide) derivative of estradiol as inhibitor of 17beta
      hydroxysteroid dehydrogenase type 1.
AB  - In an effort to develop potent agents for reducing the levels of the active
      estrogen, estradiol, we developed a new category of 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) type 1 inhibitors. The compounds described possess a
      butyl methyl alkylamide side chain linked to the C6 position of estradiol by a
      thioether. With a series of epimeric mixtures, an optimal side-chain length of
      five methylene groups (between the amide group and steroid part) was first
      determined. Thereafter, both C6 epimers of optimized mixture were obtained after
      high-pressure liquid chromatography separation. 1H and 13C NMR experiments were
      performed to confirm the stereochemistry of each epimer. The 6beta-orientation of
      the side-chain was found to be crucial for enzymatic inhibition. Indeed, for the
      optimized side-chain length, the compound with a beta-orientation (5: N-butyl,N
      methyl 7-(3',17'beta-dihydroxy-1',3',5'( 10')-estratriene-6'beta-yl)-7
      thiaheptanamide) was 70-fold more potent than the 6alpha-analog. Compound 5 did
      not inactivate 17beta-HSD type 1, suggesting a reversible inhibitor. In addition,
      it was found to be a more potent inhibitor than the substrate estrone itself or a
      panel of three known inhibitors.

PMID- 9569012
TI  - Glucocorticoid-recognizing and -effector sites in rat liver plasma membrane.
      Kinetics of corticosterone uptake by isolated membrane vesicles. III. Specificity
      and stereospecificity.
AB  - In previous papers we provided evidence for a glucocorticoid (GC) responsive site
      in a highly purified rat liver plasma membrane (PM) fraction, which has proved to
      be osmotically active, 'right side-out' vesicles, free of CBG, glucocorticoid
      receptors (GR) and ATP (J. Steroid Biochem. Molec. Biol. 42 (1992) 737-756 and
      757-771). This site, now called 'GC importer', mediates active transmembrane
      transport of corticosterone (B). Pronounced specificity, including stereo- and
      enantiomeric specificity, of ligand-GC importer interaction was demonstrated by
      competition assays using 54 different steroidal hormones and molecules. Important
      structural prerequisites for ligands with high specificity for the GC importer
      are plane C21-steroid hormones with 1-ene and/or 4-ene or 5alpha-reduced
      configuration, and/or OH-group(s) at C11beta>C17alpha>C21. Unexpectedly, other
      preferred ligands are C17alpha-ethynyl steroids like estrogens with an OH- or
      OCH3-group at C3 (EE2, mestranol) as well as progestins with C3-OH and 4-ene
      configuration (ethynodiol). C21-steroids with 11alpha-OH, 11-keto, 16alpha-CH3,
      16beta-CH3, 16alpha-OH or 5beta-reduced configuration are low specificity
      ligands. The importer even displays different specificity for enantiomers
      (levonorgestrel>L-norgestrel). Altogether, the GC importer preferentially
      recognizes active GC and natural progestins which act as GC-antagonist (e.g.
      prednisolone>11beta-cortisol = B > or = progestins). Synthetic GC-agonists (e.g.
      dexamethasone, betamethasone, triamcinolone), most synthetic progestins,
      biologically inactive GC (e.g. 11alpha-cortisol, prednisone, cortisone, 11
      dehydro-B), mineralocorticoids (aldosterone), natural estrogens (e.g. E1, E2,
      E3), DES and vitamin D3 derivatives do not interact with the GC importer. Osmotic
      shrinkage experiments revealed that interaction of high as well as low
      specificity ligands with the GC importer comprises reversible binding and
      transport through the PM. The ligand specificity profile of the GC importer and
      the GR exhibit pronounced differences, suggesting that both GC recognizing sites
      are different proteins. Performing immunoblotting, using specific mono- and
      polyclonal antibodies directed against the intracellular rat GR, of the PM
      pretreated with the membrane protein solubilizing detergent CHAPSO, we found that
      specific steroid binding to the PM site is not due to contamination with GR.
      Colchicine, daunorubicine, quinine, reserpine, verapamil and vinblastine,
      representatives of lipophilic xenobiotics which are known to be transported out
      of cells by the glycoprotein P170, did not compete with B for uptake into PM
      vesicles, indicating that the GC importer is not a member of the ABC/mdr
      superfamily. The GC importer seems to be an additional link in the chain of
      steroid signal transduction and may be functionally involved in the action of
      natural GC-agonists and GC-antagonists.

PMID- 9569014
TI  - Metabolic fate and hepatocyte toxicity of reverse amide analogs of conjugated
      ursodeoxycholate in the rat.
AB  - Reverse amide analogs of conjugated bile acids were tested for their effects on
      the viability of cultured primary rat hepatocytes, for their transport and
      metabolism in the intact rat, and for their susceptibility to hydrolysis by
      intestinal bacteria. Succinylnorursodeoxycholanylamide (SNUDCN) and its parent
      C23 amine showed the same general lack of toxicity toward hepatocytes as the
      normal conjugates of ursodeoxycholic acid, at concentrations up to 500 microM.
      The 3alpha,7alpha,12alpha-trihydroxy analog and its parent amine were more toxic
      than the corresponding dihydroxy compounds, although their effects were similar
      to those observed for the normal conjugates of cholic acid. Following
      intraduodenal infusion, greater than 80% of administered SNUDCN appeared in the
      bile of bile fistula rats. Analysis of bile fractions indicated the presence of
      SNUDCN (81.5 mol% of original amount) and two metabolites, the taurine conjugate
      of SNUDCN (9.4 mol%) and SNUDCN containing an additional hydroxy group (9.1
      mol%). Although SNUDCN underwent an efficient first pass enterohepatic
      circulation, it displayed a shorter biological half life than taurocholate (T1/2:
      8.9 h vs 39.6 h, respectively). The reverse amide analogs were not hydrolyzed by
      any of a variety of intestinal bacteria known to hydrolyze normal conjugated bile
      acids. Despite the shorter half-life, the reverse amide analogs may be of
      potential use in the targeting of therapeutic bile acids to the colon.

PMID- 9569015
TI  - Pharmacological profile of RU 58642, a potent systemic antiandrogen for the
      treatment of androgen-dependent disorders.
AB  - The pharmacological profile of RU 58642, a new non-steroidal antiandrogen was
      investigated both in vitro and in vivo. In vitro, the compound displays a strong
      and specific affinity for androgen receptor. In vivo, its antiandrogenic activity
      was evaluated in castrated rat supplemented with testosterone propionate and in
      intact animals on prostate, seminal vesicles weight and serum levels of
      testosterone by oral and subcutaneous route. In castrated rats RU 58642 induced a
      significant decrease in prostate weight at a dose as low as 0.3 mg/kg whatever
      the route of administration. In intact rats its activity was compared to that of
      other non-steroidal antiandrogens such as flutamide, nilutamide and bicalutamide.
      RU 58642 proved to be significantly more potent than the reference compounds in
      reducing prostate weight: 3-30 times orally and 3-100 times subcutaneously, and
      thus the most potent antiandrogen to date to our knowledge. These results suggest
      that this compound may be very useful in the treatment of systemic androgen
      dependent diseases.

PMID- 9569016
TI  - Expression of two aromatase cDNAs in various rabbit tissues.
AB  - Aromatase is a steroidogenic enzyme complex which catalyses the conversion of
      androgens to estrogens. In a previous study, we elucidated the structure of a 2.9
      kb aromatase cDNA from ovarian rabbit tissue. We report here, the structure of
      another shorter aromatase cDNA (1.5 kb) from the same tissue. This cDNA is likely
      to encode for a nonfunctional aromatase which would lack an heme binding domain.
      We have shown using an RT-PCR technique that rabbit placental tissue, like the
      ovarian one, expresses both the 2.9 and 1.5 kb cDNA and that the adipose tissue
      expresses the 2.9 kb cDNA. Using a 5' RACE procedure, we obtained the 5' end of
      the placental transcripts. Comparison of its sequence with the 5' end of the
      ovarian one suggests the existence of distinct exon 1 sequences for each one of
      the two tissues as already described in the human. These results point to the
      rabbit as a useful laboratory animal for studying regulation of aromatase
      expression in adipose and placental tissues.

PMID- 9569017
TI  - Evidence that immature rat liver is capable of participating in steroidogenesis
      by expressing 17alpha-hydroxylase/17,20-lyase P450c17.
AB  - Steroid hydroxylase cytochrome P450c17 has been previously purified from
      microsomal fractions of immature rat livers. In this study, we investigated the
      expression of P450c17 in rat livers to understand a role of steroidogenesis in
      the extrasteroidogenic tissue. Upon immunoblot analysis utilizing liver
      microsomes from rats, P450c17 was detected in 1 and 3 week old rats but not in
      adult rats. Data from immunohistochemical studies also showed a similar age
      dependent expression of P450c17 and indicated that P450c17 detected in immature
      rat livers is localized in cells surrounding interlobular veins. This age
      dependent expression of P450c17 in rat livers was observed in both sexes. Upon
      enzymatic analysis utilizing microsomal fractions from livers, levels of 17alpha
      hydroxylase and 17,20-lyase activity for pregnenolone and progesterone increased
      by 3 weeks and dramatically reduced at 7 weeks, which is consistent with the
      expression level of P450c17. These data clearly indicate that P450c17 is
      expressed in immature rat liver to produce 17alpha-hydroxysteroids and C19
      steroids. Based upon immunoblot analysis, the expression level of P450c17 in
      immature rat livers was approximately one third of that in testis. Compared
      expression level of P450c17 and total volume of organs between liver and testis,
      the total amount of steroid metabolites produced by liver P450c17 could be
      greater than that produced by gonadal P450c17. Because of the absence of P450c17
      in rat adrenal glands, rat liver could be the major site for producing 17alpha
      hydroxysteroids and C19-steroids in this particular period of life. Although
      physiological products formed by P450c17 in liver and their roles remain to be
      elucidated, this study suggests a large capacity of prepubertal rat liver for
      participating the production of steroid hormones and a putative importance of
      17alpha-hydroxysteroids and C19-steroids, such as cortisol and androstendione,
      which are generally believed to be minor components of steroid hormones in
      rodents.

PMID- 9569018
TI  - Regulation of the cdk inhibitor p21 gene during cell cycle progression is under
      the control of the transcription factor E2F.
AB  - The control of cell cycle progression is orchestrated by an extraordinary diverse
      and dynamic in function group of proteins. Critical in the progression are the
      actions of the E2F family of transcription factors which regulate the expression
      of genes necessary for the G1/S transition and the WAF/CIP/KIP family of cdk
      inhibitors which can inhibit cell cycle progression. In this report, we have
      identified E2F binding sites in both the human and mouse p21 promoters that bind
      E2F protein complexes from nuclear extracts in a cell cycle-dependent manner. In
      ectopic expression experiments we determined that E2F1, but not E2F4, can
      strongly transactivate the human p21 gene through these E2F binding sites which
      are located in the -215/+1 region of the p21 gene. The transactivation of the p21
      gene through regulatory elements within the -215/+1 region of the promoter was
      correlated with increased levels of endogenous E2F1 and p21 proteins at the G1/S
      boundary. The significance of transactivation of the p21 gene by E2F is that p21
      function is important in cell cycle progression as well as for cell cycle arrest.
      Indeed, E2F-induced levels of p21 protein during the G1/ S transition is
      consistent with the recent findings demonstrating that p21 acts as an assembly
      factor for kinase active cyclin/cdk/p21 complexes.

PMID- 9569019
TI  - The OMgp gene, a second growth suppressor within the NF1 gene.
AB  - The Oligodendrocyte-Myelin glycoprotein gene (OMgp) is placed within an intron of
      the NF1 gene. Neurofibromin, the product of NF1, acts as a RasGAP and suppresses
      growth; inactivating mutations in NF1 lead to neurofibromatosis type 1. We report
      that OMgp also has growth suppressive effects and downregulates mitogenic
      signaling pathways closely related to those influenced by neurofibromin.
      Overexpression of OMgp alters mitogenic signaling in NIH3T3 fibroblasts. Cells
      overexpressing OMgp grow more slowly in serum compared to controls and show a
      partial G1 block upon cell cycle analysis. PDGF is the primary mitogen for
      fibroblasts in serum. Overexpression of OMgp alters PDGF signaling in fibroblasts
      which results in a block of mitogenic signaling. PDGF induced activation of c-Src
      is blocked, as is the induction of c-Myc and c-Fos, while tyrosine
      phosphorylation of the PDGFbeta receptor, PLCgamma1 and induction of c-Jun are
      intact. Although a number of genes embedded within other genes have been
      described, the biological significance of this arrangement remains unknown. We
      demonstrate here that structurally unrelated products of two such genes may
      exercise closely related functions. Our data also raise the possibility of a role
      for OMgp in disorders of cell proliferation such as NF1.

PMID- 9569020
TI  - Herbimycin A accelerates the induction of apoptosis following etoposide treatment
      or gamma-irradiation of bcr/abl-positive leukaemia cells.
AB  - Philadelphia chromosome (Ph)-positive leukaemia cells express the chimeric
      bcr/abl oncoprotein, whose deregulated protein tyrosine kinase (PTK) activity
      antagonizes the induction of apoptosis by DNA damaging agents. Treatment of Ph
      positive K562, TOM 1 and KCL-22 cells with etoposide for 2d induced cytosolic
      vacuolation, but not nuclear condensation or DNA fragmentation. The bcr/abl
      kinase-selective inhibitor herbimycin A increased the induction of nuclear
      apoptosis by etoposide or gamma-radiation. The concentration of herbimycin
      required to synergize with etoposide was similar to that required to decrease the
      level of tyrosine phosphorylated proteins or of the protein tyrosine kinase
      activity of anti-abl immune complexes in K562 cells. The ability of herbimycin A
      to sensitize K562, TOM 1 or KCL-22 cells to apoptosis induction correlated with
      its ability to decrease the cellular content of phosphotyrosyl proteins in these
      Philadelphia-positive lines. Enhancement of nuclear apoptosis by herbimycin was
      not attributable to downregulation of the bcl-2 or bcl-XL anti-apoptotic
      proteins. In contrast, herbimycin protected Philadelphia-negative HL60 cells from
      apoptosis induction by etoposide and did not affect killing of NC37 and CEM
      cells. The data suggest that the induction of apoptosis is blocked in cells
      expressing the bcr/abl oncoprotein and that herbimycin A increases induction of
      programmed cell death following DNA damage. Selective PTK inhibitors may
      therefore be of value in securing the genetic death of Ph-positive leukaemia
      cells.

PMID- 9569021
TI  - Inhibition of cell proliferation by the interferon-inducible 204 gene, a member
      of the Ifi 200 cluster.
AB  - The role of the IFN-inducible p204 as growth regulator was investigated by
      transfecting an expression vector constitutively expressing p204 into several
      cell lines. Like pRB and p107, p204 is a potent growth inhibitor in sensitive
      cells, as demonstrated by the cell focus assay. Since stable transfectants of
      sensitive lines constitutively overexpressing p204 could not be established in
      vitro, we inserted the 204 cDNA into a vector bearing an heavy-metal-inducible
      promoter. Here we show that proliferation of B6MEF fibroblasts lacking endogenous
      p204 is strongly inhibited by transient p204 expression in the nucleus. p204
      delays G1 progression into the S-phase and cells accumulate with a DNA content
      equivalent to cells arrested in late G1. Moreover, the role of p204 in the
      control of cell growth in vivo was investigated by generating transgenic mice in
      which the Ifi 204 gene was constitutively expressed in all tissues. To this end,
      expression vectors bearing the 204 cDNA under the control of the SV40 viral
      promoter were constructed. The overexpression of the p204 transgene achieved by
      injecting fertilized mouse eggs with these vectors was compatible with embryo
      development up to the four-cell stage in an in vitro follow-up of 4.5 days.
      However, no viable animals with an intact copy of the transgene were obtained,
      suggesting that high and constitutive levels of p204 expression can impair normal
      embryo development. These findings indicate that p204 plays a negative role in
      growth regulation and provide new information about the molecular mechanisms
      exploited by IFNs to inhibit cell proliferation.

PMID- 9569022
TI  - Human normal peripheral blood B-lymphocytes are deficient in DNA-dependent
      protein kinase activity due to the expression of a variant form of the Ku86
      protein.
AB  - The heterodimeric Ku protein, which comprises a 86 kDa (Ku86) amd a 70 kDa (Ku70)
      subunits, is an abundant nuclear DNA-binding protein which binds in vitro to DNA
      termini without sequence specificity. Ku is the DNA-targeting component of the
      large catalytic sub-unit of the DNA-dependent protein kinase complex (DNA
      PK[CS]), that plays a critical role in mammalian double-strand break repair and
      lymphoid V(D)J recombination. By using electrophoretic mobility shift assays, we
      demonstrated that in addition to the major Ku x DNA complex usually detected in
      cell line extracts, a second complex with faster electrophoretic mobility was
      observed in normal peripheral blood lymphocytes (PBL) extracts. The presence of
      this faster migrating complex was restricted to B cells among the circulating
      lymphocyte population. Western blot analysis revealed that B cells express a
      variant form of the Ku86 protein with an apparent molecular weight of 69 kDa, and
      not the 86 kDa- full-length protein. Although the heterodimer Ku70/variant-Ku86
      binds to DNA-ends, this altered form of the Ku heterodimer has a decreased
      ability to recruit the catalytic component of the complex, DNA-PK(CS), which
      contributes to an absence of detectable DNA-PK activity in B cells. These data
      provide a molecular basis for the increased sensitivity of B cells to ionizing
      radiation and identify a new mechanism of regulation of DNA-PK activity that
      operates in vivo.

PMID- 9569023
TI  - Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2.
AB  - Disabled-2 (Dab2), a mammalian structural homolog of Drosophila Disabled (Dab),
      is a mitogen-responsive phosphoprotein. It has been speculated to be a negative
      regulator of growth since its expression is lost in ovarian carcinomas. Dab2
      contains a C-terminal proline-rich domain with sequences similar to those found
      in Sos, a guanine nucleotide exchange factor for Ras. The proline-rich sequences
      of Sos mediate the interaction of Sos with Grb2, an adaptor protein which coupled
      tyrosine kinase receptors to Sos. Herein, we have investigated the possibility
      that Dab2 interacts with Grb2. In experiments of co-immunoprecipitation from
      BAC1.2F5 macrophage cell lysates, significant quantities of Grb2 were associated
      with both Sos and Dab2, although Dab2 and Sos were not present in the same
      complex. Transfection of Dab2 into a Dab2-negative cell line (293 cells)
      decreased the amount of Grb2 associated with Sos, suggesting that Dab2 competes
      with Sos for binding to Grb2. Proline-rich peptides corresponding to Dab2 (#661
      669) and to Sos (#1146-1161) inhibited the binding of Dab2 to Grb2, but were less
      effective in disrupting the Grb2-Sos complex. The expressed proline-rich domain
      of Dab2 (#600-730) bound Grb2, but other regions of Dab2 failed to bind Grb2.
      Both of the individual SH3 domains of Grb2 bound to Sos (N-terminal SH3 domain >>
      C-terminal SH3 domain), but binding to Dab2 required the intact Grb2, suggesting
      cooperative binding using both SH3 domains of Grb2. These data indicate that Dab2
      binds to the SH3 domains of Grb2 via its C-terminal proline-rich sequences. Dab2
      may modulate growth factor/Ras pathways by competing with Sos for binding to
      Grb2.

PMID- 9569024
TI  - Normal developing rat brain expresses a platelet-derived growth factor B chain (c
      sis) mRNA truncated at the 5' end.
AB  - The 5' untranslated sequence (5' UTS) of platelet-derived growth factor B (PDGF
      B/c-sis) mRNA is highly preserved through evolution, and inhibits translation of
      downstream coding sequences. In this study, using Northern analysis we identified
      two PDGF-B/c-sis mRNAs (3.5 kb and 2.6 kb) expressed in normal developing rat
      brain. In contrast to the constitutive expression of 3.5 kb mRNA, the expression
      of 2.6 kb mRNA increased markedly in accordance with those stages of brain
      development at which we had previously demonstrated an increased immunoreactivity
      for PDGF-B/c-SIS in neurons (Sasahara et al., 1992). By PCR cloning and the RNase
      protection assay, we determined the complete sequence of rat PDGF-B/c-sis, and
      found that the 2.6 kb transcript was a form of the 3.5 kb message truncated at
      the 5' end, and that the predominant 2.6 kb mRNA commenced 15 nt upstream of the
      signal peptide. Accordingly, it is suggested that the truncation of 5' UTS
      contributes to the expression of PDGF-B/c-SIS protein in the CNS. Lack of
      translational inhibitory 5' UTS of PDGF-B/c-sis transcript and resultant
      efficient protein translation have been reported in only a few transformed cells
      and cultured umbilical vein endothelial cells. We have extended this knowledge to
      the developing rat brain, and suggest that a similar mechanism could operate
      widely in non-transformed tissue in vivo.

PMID- 9569025
TI  - The Ski oncoprotein interacts with Skip, the human homolog of Drosophila Bx42.
AB  - The v-Ski avian retroviral oncogene is postulated to act as a transcription
      factor. Since protein-protein interactions have been shown to play an important
      role in the transcription process, we attempted to identify Ski protein partners
      with the yeast two-hybrid system. Using v-Ski sequence as bait, the human gene
      skip (Ski Interacting Protein) was identified as encoding a protein which
      interacts with both the cellular and viral forms of Ski in the two-hybrid system.
      Skip is highly homologous to the Drosophila melanogaster protein Bx42 which is
      found associated with chromatin in transcriptionally active puffs of salivary
      glands. The Ski-Skip interaction is potentially important in Ski's transforming
      activity since Skip was demonstrated to interact with a highly conserved region
      of Ski required for transforming activity. Like Ski, Skip is expressed in
      multiple tissue types and is localized to the cell nucleus.

PMID- 9569026
TI  - Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis
      induced by selective chemotherapeutic agents.
AB  - Bax and Bcl-2 are a pair of important genes that control programmed cell death,
      or apoptosis, with Bax being the apoptosis promoter and Bcl-2 the apoptosis
      protector. Although the detailed mechanism is unknown, the protein products of
      these two genes form protein dimers with each other and the relative ratio of the
      two proteins is believed to be a determinant of the balance between life and
      death. In our preliminary study, we found that K562 erythroleukemia cells have an
      extremely low level of endogenous Bcl-2 expression and a fairly high level of
      endogenous Bax expression. We constructed Bax and Bcl-2 expression vectors and
      transfected them into K562 cells. We found that transfection of Bax vector
      increased the expression of Bax protein; a shortened form of Bax also appeared.
      Cell death analysis using the Annexin V assay showed that the Bax vector caused
      significantly more apoptotic cells that the Bcl-2 or pCI-neo vector did. After
      selection with G418, Bax, Bcl-2 and pCI-neo stably transfected cells were
      established. These three cell lines were examined for their response to the
      chemotherapeutic agents ara-C, doxorubicin, etoposide and SN-38. Bax-K562 cells
      showed significantly higher fractions of apoptotic cells than pCI-neo-K562 cells
      when treated with ara-C, doxorubicin or SN-38. No sensitization effect was seen
      when etoposide was used. In contrast, Bcl-2-K562 cells had fewer apoptotic cells
      than pCI-neo-K562 cells after treatment with all these agents. Therefore, Bax may
      sensitize K562 cells to apoptosis induced by a wide range of, but not all,
      chemotherapeutic agents.

PMID- 9569027
TI  - Stable reintroduction of wild-type P53 (MTmp53ts) causes the induction of
      apoptosis and neuroendocrine-like differentiation in human ductal pancreatic
      carcinoma cells.
AB  - Pancreatic ductal adenocarcinoma is one of the major causes of cancer mortality
      in the industrialized world, having among the poorest prognosis of any
      malignancy. Mutations or alterations in the p53 tumor suppressor gene/protein are
      observed in 50-70% of these cancers, yet little information is available
      regarding the phenotypic effects of restoration of wild-type (wt) p53 function in
      pancreatic ductal carcinoma cells. The consequences of stable reintroduction of
      wt p53 on apoptosis and differentiation was examined in a poorly differentiated
      pancreatic carcinoma cell line (Panc-1), possessing only mutant (mt) p53 (codon
      273 mutation). Cells were transfected with a temperature-sensitive mouse
      p53val135 (tsp53) vector under additional control of a genetically-modified
      metallothionein promoter. This tsp53 has a 'mt' phenotype at 37.5 degrees C, and
      a 'wt' phenotype at 32.5 degrees C and the presence of 100 microM ZnCl2. Stable
      expression of wt p53 caused upregulation of the p21/WAF1 gene, and G1 growth
      arrest as shown by flow cytometry and BrdU labeling. Additionally, apoptosis was
      induced 8-12 post-induction in the majority of the cells (60-70%), as
      demonstrated by morphological changes, in situ TdT labeling and internucleosomal
      laddering. However, a subpopulation (30%) of the transfectants survived this
      apoptotic fate. Unlike the epithelial parental Panc-1 cells, these cells
      exhibited the appearance of a neuroendocrine-like phenotype with extensive branch
      like processes, and marked cytoplasmic and cytoskeletal immunostaining for tau-2,
      synaptophysin, and chromogranin A. These studies suggest that stable and
      regulated expression of wt p53 can have multiple phenotypic consequences
      (apoptosis and altered differentiation to a neuroendocrine-like phenotype) in
      poorly-differentiated pancreatic carcinoma cells.

PMID- 9569028
TI  - Overexpression of MDM2, due to enhanced translation, results in inactivation of
      wild-type p53 in Burkitt's lymphoma cells.
AB  - Numerous studies have indicated that inactivation of p53 is one of the essential
      requirements for the unrestrained growth of tumoral cells. When the status of the
      p53 gene was examined in various types of lymphoid malignancies, mutations in p53
      have been predominantly detected in Burkitt's lymphoma (BL) cells, therefore
      suggesting that alteration of p53 could specifically contribute to the malignant
      phenotype of these tumoral cells. In addition to mutations, functional
      inactivation of p53 can also occur through interaction of the wild-type gene
      product with various viral or cellular proteins. The cellular MDM2 protein, for
      example, is able to inhibit p53 tumor suppressor function by concealing its
      transactivation domain. Mdm2 gene amplification has been described in several
      types of sarcomas, resulting in overexpression of the MDM2 protein. In this
      study, we have examined the status of MDM2 and p53 in 20 BL cell lines. Four were
      found to contain wild-type p53 and to overexpress MDM2 protein. Within these BL
      cells, both molecules are physically associated since they can be co-precipitated
      and p53 is inactivated as cells neither arrest in G1 nor enter apoptosis
      following gamma-radiation. We also report that the high level of the MDM2 protein
      in BL cells is neither associated with an amplification of the mdm2 gene nor with
      an elevated level of RNA or an increased protein stability, but is rather due to
      an enhanced translation ability of the mdm2 RNA. These results indicate that in
      certain BL cells, overexpression of MDM2 protein regulated at the
      posttranscriptional level, induces an escape from p53-controlled cell growth.

PMID- 9569029
TI  - Differential expression of fos and jun family members in the developing chicken
      gastrointestinal tract.
AB  - We have analysed the expression patterns of all the known fos/jun family genes,
      which encode the components of the transcription factor AP-1, in the chicken
      embryonic digestive tract that develops into the esophagus, proventriculus,
      gizzard, small intestine, ceca and large intestine. From soon after formation of
      the tubular structure, each gene transcript was localized in distinct domains of
      the epithelium and mesenchyme in all of these major gastrointestinal organs,
      independently of the anterior-posterior axis. fra-2 was expressed predominantly
      in epithelium, which also expressed junD, while low-level expression of junD was
      also detected in smooth muscle cell precursors in mesenchyme. Expression of c-jun
      and c-fos was detectable in both mesenchyme and epithelium through the whole
      tract. In the differentiated proventriculus, the developed glandular epithelium
      expressed c-jun and junD, but not fra-2, while luminal epithelium expressed fra-2
      and junD, but not c-jun. These results suggest that distinct Fos/Jun protein
      heterodimers play important roles in maintaining the epithelial-mesenchymal
      interactions. Similar expression patterns to those of fra-2 and junD were
      established from earlier stages by Sonic hedgehog gene and the Indian hedgehog
      gene, respectively, both of which are important in forming the inductive network
      between epithelium and mesenchyme of the digestive tract.

PMID- 9569030
TI  - The role of MAP4 expression in the sensitivity to paclitaxel and resistance to
      vinca alkaloids in p53 mutant cells.
AB  - Mutations in p53 change the sensitivity to cancer chemotherapeutic drugs. Whereas
      many drugs, including the vinca alkaloids, often become less effective when p53
      is transcriptionally inactivated, several, most notably paclitaxel, may become
      more effective. In studying the underlying mechanism(s), we found that increased
      MAP4 expression, which occurs with transcriptionally silent p53, is associated
      with increased sensitivity to paclitaxel and decreased sensitivity to vinca
      alkaloids. Using murine fibroblasts transfected with MAP4, we directly
      demonstrated that the changes in drug sensitivity were associated with parallel
      alterations in drug-induced apoptosis and cell-cycle arrest. Immunofluorescent
      staining of the microtubule network revealed that cells with increased MAP4
      expression displayed an increase in polymerized microtubules and an increased
      binding of fluorsceinated paclitaxel. Since MAP4 stabilizes polymerized
      microtubules, overexpression of this gene provides a plausible mechanism to
      explain the altered sensitivity to microtubule-active drugs in the presence of
      mutant p53.

PMID- 9569031
TI  - The EWS/ATF1 fusion protein contains a dispersed activation domain that functions
      directly.
AB  - Naturally occurring chromosomal fusion of the Ewings Sarcoma Oncogene (EWS) to
      distinct cellular transcription factors, produces aberrant transcriptional
      activators that function as dominant oncogenes. In Malignant Melanoma of Soft
      Parts the N-terminal region of EWS is fused to C-terminal region of the cAMP
      inducible transcription factor ATF1. The EWS/ATF1 fusion protein binds to ATF
      sites present in cAMP-responsive promoters via the ATF1 bZIP domain and activates
      transcription constitutively in a manner that is dependent on an activation
      domain (EAD) present in EWS. To further define the requirements for trans
      activation we have performed mutational analysis of EWS/ATF1 in mammalian cells
      and report several new findings. First, trans-activation by EWS/ATF1 does not
      require dimerisation with other ATF family members present in mammalian cells.
      Second, in contrast to the earlier suggestion of an allosteric role, the EAD can
      act directly. Third, determinants of trans-activation are dispersed throughout
      the EAD and cooperate synergistically to produce potent trans-activation. We also
      report that the region of EWS containing the EAD can activate transcription in
      Yeast. This latter finding might enable a genetic approach to understanding the
      mechanism of transcriptional activation by EWS and development of high-throughput
      screens for EWS inhibitors.

PMID- 9569032
TI  - Genomics and transcription analysis of human TFIID.
AB  - TFIID, a multisubunit protein comprised of TBP (TATA box-binding protein) and
      TAF(II)s (TBP-associated factors), has a central role in transcription initiation
      at class II promoters. TAF(II)s role as mediators of regulatory transcription
      factors, such as pRb and p53, and their involvement in signal transduction
      pathways suggest that some may participate in the control of cell proliferation
      and differentiation: therefore, they could be considered potential protooncogenes
      or antioncogenes. With the aim of starting to analyse these potential roles, we
      have determined the genomic position of nine human TAF(II) genes (TAF[II]250,
      TAF[II]135, TAF[II]100, TAF[II]80, TAF[II]55, TAF[II]43, TAF[II]31, TAF[II]28,
      TAF[II]20/15) and of two previously unknown sequences related to TAF(II)250 and
      TAF(II)31, respectively. Except for those encoding TAF(II)250 and TAF(II)31,
      these genes are present in a single copy and, with the exclusion of those for
      TAF(II)43 and TAF(II)28 (both at 6p21), are localized in different segments of
      the genome. Indeed, six of them map to a chromosomal region commonly altered in
      specific neoplasias, which defines them as candidates for involvement in
      oncogenesis. Our experiments also demonstrate that TAF(II) transcripts are
      synthesized ubiquitously, mostly at low levels similar to those of TBP.
      Interestingly, the amount of the major mRNA species detected by TAF(II)20/15 cDNA
      is higher, which suggests that the polypeptide it encodes may also perform
      functions independently of TFIID. TAF(II) isoforms, indicated by additional bands
      on Northern blots, may play a role in modulation of TFIID function. These data
      will be useful for analysing variations of TAF(II) mRNA phenotype during cell
      proliferation, differentiation and development, both normal and pathological.

PMID- 9569033
TI  - Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involvement
      in benign surface epithelial ovarian tumours.
AB  - A detailed long range restriction map of the region defined by markers D6S149 and
      D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning
      and contig assembling of the same region. Seven YAC clones were found to span the
      almost 1000 Kb region flanked by the two markers which on the genetic map
      resulted to be 1.9 cM apart. With some of the characterized YAC clones we
      undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The
      rationale for this was the recent mapping to a region of chromosome 6q27, flanked
      by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of
      human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region
      (comprised in the larger D6S281-D6S133 physical interval) was altered in all
      samples analysed adding support to the occurrence of a immortalization step in
      this type of tumors.

PMID- 9569034
TI  - Chromosome division figures reveal genomic instability in tumorigenesis of human
      colon mucosa.
AB  - A variety of chromosomal gains and losses has been detected with comparative
      genomic hybridization during tumorigenesis in the colon mucosa. The aim of this
      investigation was to corroborate increasing genomic instability and to elucidate
      those lesions in which the record from comparative genomic hybridization has
      remained unexpectedly negative. Replicate paraffin-embedded samples were
      investigated in detail using image microphotometry. Crucial to the recent
      approach was the fact that the histological compartments were exactly matched and
      that the single-cell measurements were highly accurate (CV at 0.05). Feulgen DNA
      was quantified in interphase nuclei and chromosome division figures, which were
      found in all cases of high-grade dysplasia and, with increased frequency, of
      colon carcinoma. The genomic imbalance in chromosome division figures was
      quantified by the sensitive 4.5 c exceeding rate (where c is the haploid genome
      equivalent), which was also positive in cases with a negative record from
      comparative genomic hybridization. The DNA content of chromosome division figures
      was measured with a mean 4.5 c exceeding rate of 25.8 +/- 4.4% standard error in
      12 cases of high-grade dysplasia and of 62.1 +/- 7.1% in colon carcinoma (16
      cases). The chromosome division figures were considered to be the first
      morphological manifestation of genomic instability attending precancerous
      conditions in the colon. Telophase-like chromosome division figures with unequal
      amounts of DNA in their hemispheres revealed gross somatic mutations before
      clonal selection.

PMID- 9569035
TI  - Two Li-Fraumeni syndrome families with novel germline p53 mutations: loss of the
      wild-type p53 allele in only 50% of tumours.
AB  - We describe two Li-Fraumeni syndrome families. Family A was remarkable for two
      early childhood cases of adrenocortical tumours, family B for a high incidence of
      many characteristic cancers, including a childhood case of choroid plexus tumour.
      Using direct sequencing, we analysed exons 5-9 of the p53 gene in constitutional
      DNA of individuals from both families and found two novel germline mutations in
      exon 5. In family A, we detected a point substitution in codon 138 (GCC to CCC),
      which resulted in the replacement of the alanine by a proline residue. Family B
      harboured a single-base pair deletion in codon 178 (CAC to -AC), resulting in a
      frameshift and premature chain termination. Three out of six tumours examined
      from both families, a renal cell carcinoma, a rhabdomyosarcoma and a breast
      cancer, showed loss of heterozygosity and contained only the mutant p53 allele.
      The remaining three neoplasms, both adrenocortical tumours and the choroid plexus
      tumour retained heterozygosity. Immunohistochemistry with anti-p53 antibody
      confirmed accumulation of p53 protein in tumours with loss of heterozygosity,
      while the remaining tumours were p53 negative. These results support the view
      that complete loss of activity of the wild-type p53 need not be the initial event
      in the formation of all tumours in Li-Fraumeni individuals.

PMID- 9569036
TI  - Enhanced expression of cytochrome P450 in stomach cancer.
AB  - The cytochromes P450 have a central role in the oxidative activation and
      detoxification of a wide range of xenobiotics, including many carcinogens and
      several anti-cancer drugs. Thus the cytochrome P450 enzyme system has important
      roles in both tumour development and influencing the response of tumours to
      chemotherapy. Stomach cancer is one of the commonest tumours of the alimentary
      tract and environmental factors, including dietary factors, have been implicated
      in the development of this tumour. This type of tumour has a poor prognosis and
      responds poorly to current therapies. In this study, the presence and cellular
      localization of several major forms of P450, CYP1A, CYP2E1 and CYP3A have been
      investigated in stomach cancer and compared with their expression in normal
      stomach. There was enhanced expression of CYP1A and CYP3A in stomach cancer with
      CYP1A present in 51% and CYP3A present in 28% of cases. In contrast, no P450 was
      identified in normal stomach. The presence of CYP1A and CYP3A in stomach cancer
      provides further evidence for the enhanced expression of specific forms of
      cytochrome P450 in tumours and may be important therapeutically for the
      development of anti-cancer drugs that are activated by these forms of P450.

PMID- 9569037
TI  - Lack of involvement of known oncogenic DNA viruses in Epstein-Barr virus-negative
      Hodgkin's disease.
AB  - Epstein-Barr virus (EBV) is associated with around one-third of cases, but young
      adult cases are rarely EBV associated. In this study, known oncogenic DNA
      viruses, including human adenoviruses, papovaviruses and the human herpesviruses
      6 (HHV-6) and -8 (HHV-8) were not detected in Hodgkin's disease lesions. These
      results suggest that an as yet unidentified infectious agent is involved in the
      pathogenesis of non-EBV-associated Hodgkin's disease.

PMID- 9569038
TI  - Evaluation of FHIT gene alterations in ovarian cancer.
AB  - The FHIT gene, recently cloned and mapped on chromosome 3p14.2, has frequently
      been found to be abnormal in several established cancer cell lines and primary
      tumours. As alterations of chromosome 3p are common events in ovarian cancers
      with breakpoint sites at 3p14.2, we decided to investigate the role of FHIT in
      human ovarian tumorigenesis. Fifty-four primary ovarian carcinomas were studied
      by reverse transcription of FHIT mRNA followed by polymerase chain reaction (PCR)
      amplification and sequencing of products. The same tumours and matched normal
      tissues were also investigated for loss of heterozygosity using three
      microsatellite markers located inside the gene. We found an abnormal transcript
      of the FHIT gene in two cases (4%) and allelic losses in eight cases (15%).
      Twelve (22%) of the 54 tumours investigated belonged to young patients with a
      family history of breast/ovarian cancer. In none of these cases was the FHITgene
      found to be altered. Our results indicate that FHITplays a role in a small
      proportion of ovarian carcinomas.

PMID- 9569039
TI  - Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility,
      proliferation and morphology.
AB  - The expression of hepatocyte growth factor/scatter factor (HGF/SF) was studied in
      12 mesothelioma cell lines characterized by either an epithelioid or a fibroblast
      like phenotype. Conditioned media from these lines were analysed by bioassay and
      ELISA, and HGF/SF was detected in three cell lines, all with a fibroblast-like or
      mixed morphology. None of eight epithelioid cell lines expressed the factor.
      Thus, for these cell lines, the ability to secrete HGF/SF correlated with the
      cell phenotype. Following on from these observations, two cell lines, BR and BT,
      with a fibroblast-like and an epithelioid phenotype, respectively, were further
      investigated. Both cell lines expressed the Met receptor but only BR secreted
      HGF/SF. Both cell lines responded to exogenous HGF/SF treatment by a change of
      morphology but in different ways: BR became more elongated and bipolar, while BT
      formed more spread-out cell colonies. HGF/SF acted as a paracrine effector on the
      epithelioid BT cells and stimulated both cell-spreading and proliferation.
      Interestingly, BT cells spread but did not scatter in response to exogenous
      HGF/SF. In contrast BR cells showed only some stimulation of cell motility with
      HGF/SF and no increase in cell proliferation was observed. Because HGF/SF was
      previously found in the pleural effusion fluids of patients with malignant
      mesothelioma and in paraffin-embedded tumour tissues, it is concluded that HGF/SF
      may well stimulate the growth and spread of malignant mesothelioma in vivo by
      paracrine and/or autocrine mechanisms.

PMID- 9569040
TI  - Mutations of K-ras oncogene in human adrenal tumours in Taiwan.
AB  - Recently, we have found a high frequency of p53 gene mutations in human
      functional adrenal tumours. As the tumorigenesis is a multigene defect, we
      believe that other oncogenes may also be involved in the initiation or
      progression of adrenal tumours. Using the single-strand conformational
      polymorphism (SSCP) method, we chose the ras oncogenes as the target in this
      screening procedure because their high mutation rates were detected in thyroid
      tumours. For the ras oncogenes analysed, exon 1 to exon 2 of H-ras and K-ras
      genes in the tumour tissues of 13 Conn's syndrome, two adrenal Cushing's
      syndrome, two non-functional adrenal tumours, one adrenocortical hyperplasia and
      eight phaeochromocytomas and its paired adjacent normal adrenal tissues were
      amplified and sequenced. No mutations were detected in the H-ras gene. But
      mutations of the K-ras gene were detected in 46% (6 of 13) of Conn's syndrome;
      the hot spots were located at codon 15, 16, 18 and 31, which were different from
      those previously found in other tumours (codon 12, 13 and 61). Northern blot
      analysis with 1.1 kb K-ras cDNA revealed that K-ras mRNA was more than tenfold
      over-expressed in four of Conn's syndrome, one case of Cushing's syndrome and one
      case of adrenocortical hyperplasia. The mutation sites and mutation type were not
      found in other tissues, which conferred that this was highly related to
      adrenocortical tumours. Yet, the correlation between K-ras oncogene and
      adrenocortical tumours needs to be clarified by further studies.

PMID- 9569041
TI  - The role of transforming growth factor alpha production and ErbB-2 overexpression
      in induction of tumorigenicity of lung epithelial cells.
AB  - Over-expression of erbB-2 is associated with shortened survival of patients with
      lung adenocarcinomas. We demonstrated that human lung epithelial cells,
      overexpressing erbB-2, formed tumours in nude mice only when high levels of
      transforming growth factor (TGF)-alpha were produced (E6T cells). To define the
      role that TGF-alpha production played in induction of tumorigenicity, a non
      tumorigenic TGF-alpha-negative clone of ErbB-2 overexpressing cells (E2 cells)
      was transfected with an expression vector for TGF-alpha (E2alpha cells).
      Transfected clones produced TGF-alpha at 11-25% of the level produced by the E6T
      cell line. Tumorigenic E6T cells transfected with a TGF-alpha antisense vector
      (E6TA cells) expressed only 6% of the TGF-alpha level of the parental cells.
      Clones of E6T, E6TA, E2 and E2alpha were inoculated into athymic nude mice to
      measure tumorigenic potential. E6T cells formed tumours with a 70% efficiency.
      E2, E6TA and E2alpha cells failed to form tumours. The levels of EGFR were
      similar in non-tumorigenic E2 and tumorigenic E6T cells but higher in E2alpha and
      E6TA cells, and ErbB-2 were greatly overexpressed in an E2alpha clone. In vitro,
      ErbB-2 co-immunoprecipitated with EGFR in lysates of unstimulated E6T and E2alpha
      TGF-alpha-producing cells, indicating that the lower TGF-alpha levels were
      sufficient to induce in vitro heterodimerization. These studies suggest that
      induction of the tumorigenic phenotype depends on achieving a threshold level of
      TGF-alpha sufficient to activate downstream signalling by ErbB-2 containing
      active heterodimers.

PMID- 9569042
TI  - Interleukin 2 restores CD3-zeta chain expression but fails to generate tumour
      specific lytic activity in tumour-infiltrating lymphocytes derived from human
      colorectal hepatic metastases.
AB  - Metastatic colorectal cancer is usually progressive despite infiltration of the
      tumours by T lymphocytes, suggesting that these tumour-infiltrating lymphocytes
      (TILs) are functionally deficient. Recently, TILs from other tumours have been
      shown to express reduced levels of the T-cell receptor signal-transducing CD3
      zeta chain. We were interested to determine whether a similar abnormality existed
      in TILs from human colorectal hepatic metastasis (CHM) and, if so, whether
      correcting the abnormality in vitro would restore anti-tumour activity and
      provide support for the development of immunotherapy for colorectal hepatic
      metastases. Twelve of 19 TILs from colorectal hepatic metastases were
      successfully expanded in vitro in high-dose recombinant interleukin 2 (rlL-2) and
      their specific anti-tumour cytolytic activity was determined. CD3-positive (CD3+)
      TILs were HLA-Drhigh and CD69high, suggesting that they had been activated by
      exposure to antigen but expressed low levels of CD25, CD71 and the nuclear
      proliferation antigen Ki-67. Furthermore, they showed reduced expression of CD3
      zeta compared with autologous peripheral blood T cells (PBTs) and failed to
      proliferate in the absence of high-dose rIL-2. Expansion of TILs in rIL-2
      resulted in restoration of CD3-zeta expression and the ability to lyse K562 and
      Daudi cells but not autologous tumour cells. The absence of autologous tumour
      specific cytolytic T-cell (CTL) activity may be due to the poor immunogenicity of
      colorectal tumour cells, which we found expressed only low levels of MHC I
      antigens and CD54 and failed to express MHC II antigens or the co-stimulatory
      molecules CD80, CD86 or CD106. The inability of rIL-2 to generate tumour-specific
      CTLs despite restoration of CD3-zeta expression and the presence of an intact
      lytic mechanism suggests that successful immunotherapy may require the
      development of strategies to increase the immunogenicity of this tumour.

PMID- 9569043
TI  - Complex karyotypes in flow cytometrically DNA-diploid squamous cell carcinomas of
      the head and neck.
AB  - In squamous cell carcinoma of the head and neck (SCCHN), DNA ploidy as determined
      by flow cytometry (FCM) has been found to yield prognostic information but only
      for tumours at oral sites. Cytogenetic findings have indicated complex karyotype
      to be a correlate of poor clinical outcome. In the present study, 73 SCCHN were
      investigated with the two techniques. Aneuploid cell populations were identified
      in 49 (67%) cases by FCM but in only 21 (29%) cases by cytogenetic analysis. The
      chromosome index (CI), calculated as the mean chromosome number divided by 46,
      was compared with the respective DNA index (DI) obtained by FCM in 15 tumours,
      non-diploid according to both techniques, DI being systematically 12% higher than
      CI in this subgroup. Eight (33%) of the 24 tumours diploid according to FCM had
      complex karyotypes, three of the tumours being cytogenetically hypodiploid, three
      diploid and two non-diploid. The findings in the present study may partly explain
      the low prognostic value of ploidy status as assessed by FCM that has been
      observed in SCCHN. In addition, we conclude that FCM yields information of the
      genetic changes that is too unspecific, and that cytogenetic analysis shows a
      high rate of unsuccessful investigations, thus diminishing the value of the two
      methods as prognostic factors in SCCHN.

PMID- 9569044
TI  - Expression of gamma-glutamylcysteine synthetase (gamma-GCS) and multidrug
      resistance-associated protein (MRP), but not human canalicular multispecific
      organic anion transporter (cMOAT), genes correlates with exposure of human lung
      cancers to platinum drugs.
AB  - We examined the steady-state levels of mRNA for gamma-glutamylcysteine synthetase
      (gamma-GCS), multidrug resistance-associated protein (MRP) and human canalicular
      multispecific organic anion transporter (cMOAT) in human lung cancer specimens to
      elucidate their roles in relation to platinum drug resistance in vivo. Seventy
      six autopsy samples (38 primary tumours and their corresponding normal lung
      tissues) obtained from 38 patients were analysed using the quantitative reverse
      transcription polymerase chain reaction (RT-PCR) method. Both subunits (heavy and
      light subunits) of gamma-GCS expression levels of normal lung and tumour tissues
      exposed to platinum drugs during life were significantly higher than those of non
      exposed tissues, whereas only the MRP expression levels of tumours were elevated
      in association with ante-mortem platinum drug exposure. The gamma-GCS and MRP
      expression levels correlated significantly. The cMOAT expression levels did not
      correlate with ante-mortem platinum drug exposure. Next, we monitored gamma-GCS
      heavy subunit expression levels in peripheral mononuclear cells of eight
      previously untreated lung cancer patients after platinum drug administration,
      which revealed that these drugs induced gamma-GCS expression in vivo. These
      results suggest that gamma-GCS expression is induced by platinum drugs in vivo
      and/or the physiological stress response to xenobiotics.

PMID- 9569046
TI  - The proteasome inhibitor lactacystin induces apoptosis and sensitizes chemo- and
      radioresistant human chronic lymphocytic leukaemia lymphocytes to TNF-alpha
      initiated apoptosis.
AB  - Apoptosis can be triggered by cytotoxic agents and radiation currently used in
      cancer treatment. However, the apoptotic response appears to vary between cell
      types (normal or transformed) and between types of malignancy. Thus, irradiation
      induces apoptosis in normal human lymphocytes but not in lymphocytes derived from
      a subset of chronic lymphocytic leukaemia (CLL). Moreover, in this subset,
      spontaneous apoptosis is inhibited by irradiation. Why irradiation does not allow
      the initiation of the apoptotic death pathway could be explained, at least in
      part, and in agreement with recent findings on experimental models, by the
      activation of the transcriptional factor NF-kappaB, which is able to inhibit
      apoptotic cell response. Low doses (at which no effect is observed with normal
      human lymphocytes) of the highly specific proteasome inhibitor lactacystin are
      sufficient to trigger apoptosis in these malignant cells. Proteasome inhibition
      by lactacystin prevents the nuclear translocation of both p50 and p65 NF-kappaB
      subunits and sensitizes these cells to apoptosis by tumour necrosis factor (TNF)
      alpha treatment. As this subset of CLL is totally resistant to any treatment,
      proteasome inhibition by lactacystin provides a new therapeutic approach to be
      explored, considering the sensitivity of malignant CLL-derived lymphocytes to be
      quite different from that of normal human lymphocytes.

PMID- 9569045
TI  - Endogenous antioxidant enzymes and glutathione S-transferase in protection of
      mesothelioma cells against hydrogen peroxide and epirubicin toxicity.
AB  - We have previously shown that cultured malignant mesothelioma cells contain
      elevated manganese superoxide dismutase (MnSOD) mRNA levels and activities
      compared with non-malignant mesothelial cells. As many cytotoxic drugs generate
      both superoxide and hydrogen peroxide, we assessed the relative significance of
      catalase and the glutathione redox cycle, as well as glutathione S-transferase
      (GST), in protecting these cells against hydrogen peroxide and epirubicin
      toxicity. Mesothelioma cell lines containing high (M38K cells) and low (M14K
      cells) MnSOD, and non-malignant MeT-5A mesothelial cells were selected for the
      study. M38K cells were the most resistant of these three cell types to hydrogen
      peroxide (0.1-0.5 mM, 4 h) and epirubicin (0.1-0.5 microg ml(-1), 48 h) as judged
      by lactate dehydrogenase (LDH) release and by high-energy nucleotide (ATP, ADP,
      AMP) depletion. Total glutathione was higher in M38K cells (63.8 +/- 20.3 nnmol
      mg(-1) protein) than in M14K (25.2 +/- 8.2 nmol mg[-1]) or MeT-5A cells (23.5 +/-
      4.5 nmol mg[-1]). Furthermore, GST specific activity was higher in M38K cells
      (111.3 +/- 15.8 U mg[-1]) than in M14K cells (77.4 +/- 6.6 U mg[-1]) or in MeT-5A
      cells (68.8 +/- 7.6 U mg[-1]). Western blotting indicated the presence of GST-pi
      in all these cells, the reactivity again being highest in M38K cells. Depletion
      of glutathione by buthionine sulphoximine and inhibition of catalase by
      aminotriazole enhanced hydrogen peroxide toxicity in all cell types, while only
      the depletion of glutathione increased epirubicin toxicity. We conclude that
      simultaneous induction of multiple antioxidant enzymes can occur in human
      mesothelioma cells. In addition to the high MnSOD activity, hydrogen peroxide
      scavenging antioxidant enzymes, glutathione and GST can partly explain the high
      hydrogen peroxide and epirubicin resistance of these cells in vitro.

PMID- 9569047
TI  - The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in
      seven cervix carcinoma cell lines.
AB  - The single-cell gel electrophoresis (comet) assay was used to measure radiation
      produced DNA double-strand breaks (dsbs) in a series of seven cervical tumour
      cell lines (ME180, HT3, C33A, C41, SiHa, MS751 and CaSki). The proportion of DNA
      dsbs was measured immediately after radiation treatment (initial damage) and 16 h
      later after incubation at 37 degrees C (residual damage). Linear dose-response
      curves were seen for initial (slopes 0.23-0.66) and residual (slopes 0.16-0.87)
      DNA dsbs. Neither of the slopes of the linear regression analysis on the initial
      and on the residual DNA dsbs dose-response curves (range 0-80 Gy) correlated with
      SF2 (surviving fraction at 2 Gy) measured after high- (HDR) or low-dose-rate
      (LDR) irradiation. An association was evident between SF2 after HDR and LDR
      irradiation and the ratio of the absolute level of initial and residual damage
      after a single dose of 60 Gy. However, a significant correlation was found
      between HDR (r= -0.78, P = 0.04) and LDR (r = -0.86, P = 0.03) SF2 values and the
      ratio of the slopes of the initial and residual DNA dsbs dose-response curves
      (range 0.47-0.99), representing the fraction of DNA damage remaining. These
      results indicate that the neutral comet assay can be used to predict
      radiosensitivity of cervical tumour cell lines by assessing the ratio of initial
      and residual DNA dsbs.

PMID- 9569048
TI  - Intratumour injection of immunoglobulins labelled with the alpha-particle emitter
      211At: analyses of tumour retention, microdistribution and growth delay.
AB  - To determine the effects of 211At-labelled antibodies in solid tumour tissue,
      nude mice carrying OHS human osteosarcoma xenografts received intratumour
      injections at dosages of 1, 2 or 4 MBq (-1) tumour. The radioisotope was
      conjugated to either the osteosarcoma-specific monoclonal antibody TP-3 or the
      non-specific polyclonal antibody hlgGkappa. Tumour retention of injected
      radioimmunoconjugate (RIC), measured as the percentage of injected activity
      dosage per gram, was significantly higher for the [211At]TP-3 (203 +/- 93 at 24.1
      h post injection) compared with the [211At]hlgGkappa (57 +/- 22 at 23.2 h post
      injection). The radioactive count rates in body (measured at neck and abdomen)
      were significantly lower with the TP-3 than with the hlgGkappa.
      Microautoradiography of the tumour radionuclide distribution was different for
      the two RICs, i.e. the [211At]TP-3 was to a larger extent concentrated near the
      injection site, whereas the [211At]hlgGkappa was more evenly distributed all over
      the tumour. The tumour growth was significantly delayed as a function of the
      injected activity dosage but without significant difference between the specific
      and the non-specific RIC. According to this study, it is possible to deliver
      highly selective radiation doses to solid tumours using intratumour injection of
      alpha-particle-emitting RICs. Improved tumour retention caused by antigen binding
      indicates that reduced normal tissue exposure can be obtained with antigen
      specific antibodies. The heterogeneous tumour dose distribution observed is,
      however, a major impediment to the use of alpha-particle emitters against solid
      tumours.

PMID- 9569049
TI  - Linomide blocks angiogenesis by breast carcinoma vascular endothelial growth
      factor transfectants.
AB  - The blocking of angiogenesis provides a novel therapeutic target to inhibit
      tumour spreading. In this study, we investigated the effect of linomide on
      angiogenesis induced in vivo by highly angiogenic breast carcinoma cells. The
      rabbit cornea was used to assess neovascular growth in the absence of a tumour
      mass. MCF-7 cells stably transfected with the cDNA encoding for vascular
      endothelial growth factor 121 (VEGF121) (V12 clone) were used to elicit a potent
      VEGF-dependent corneal angiogenesis. After tumour cell implant, albino rabbits
      received 100 mg kg(-1) day(-1) linomide for 5 consecutive days. Daily observation
      of neovascular progression indicated that linomide blocked angiogenesis. The
      antiangiogenic effect of linomide was apparent within 48 h from the beginning of
      the treatment and was both angiosuppressive and angiostatic. The block of
      neovascular growth lasted over 10 days from treatment suspension, and preformed
      vessels, which had regressed, remained dormant, suggesting the persistence of
      unfavourable conditions for capillary progression. Linomide (50-200 microg ml[
      1]) was not cytotoxic in vitro on resting capillary endothelial cells but blocked
      endothelial cell replication induced by VEGF. Our data indicate that linomide can
      efficiently and persistently block VEGF-dependent angiogenesis in vivo in the
      absence of a growing tumour mass. These data suggest that linomide could be a
      chemopreventive drug in breast cancer patients and a valuable tool in clinical
      settings in which metastatic spreading occurs in the absence of a detectable
      tumour mass.

PMID- 9569050
TI  - Mutations in residues of TP53 that directly contact DNA predict poor outcome in
      human primary breast cancer.
AB  - The tumour-suppressor gene TP53 is frequently mutated in breast tumours, and the
      majority of the mutations are clustered within the core domain, the region
      involved in DNA binding. We searched for alterations in this central domain of
      the TP53gene in 222 human breast cancer specimens using polymerase chain reaction
      single-strand conformation analysis (PCR-SSCA) followed by sequencing. TP53 gene
      mutations were observed in 66 tumours (31%), including three tumours that contain
      two mutations. Fifty-four (78%) of these mutations were missense point mutations,
      one was a nonsense mutation and four were deletions and/or insertions causing
      disruption of the protein reading frame, whereas four mutations were either
      silent or a polymorphism (at codon 213; n = 6). Interestingly, the majority of
      missense mutations were observed at codon 248. The outcome has been related with
      patient and tumour characteristics, and with prognosis in 177 patients who were
      eligible for analysis of both relapse-free and overall survival (median survival
      for patients alive was 115 months). There was no significant association between
      the frequency of TP53 mutations and menopausal or nodal status, or tumour size.
      In a Cox univariate analysis, TP53 gene mutation was significantly associated
      with poor relapse-free survival (RFS: P = 0.02) but not with overall survival
      (OS: P = 0.07). In a Cox multivariate analysis, including classical prognostic
      factors, TP53 gene mutation independently predicted poor RFS and OS (RHR = 1.8
      and 1.6 respectively). Unexpectedly, the median relapse-free survival of patients
      with a polymorphism at codon 213 or with a silent mutation was shorter (median 11
      months) than the median relapse-free survival of patients with or without a TP53
      gene mutation (median 34 or 48 months respectively). In an exploratory subset
      analysis, mutations in codons that directly contact DNA were related with the
      poorest relapse-free (P < 0.05) and overall survival (P < 0.02). These data imply
      that in the analysis of the prognostic value of TP53, the type of mutation and
      its biological function should be considered.

PMID- 9569051
TI  - The prognostic value of CD44 isoform expression in endometrial cancer.
AB  - Isoforms of the transmembrane glycoprotein CD44 have been implicated in tumour
      cell adhesion, tumour differentiation and metastatic spread in various human
      malignancies. We investigated the expression of CD44 isoforms containing variant
      exons v3, v5, v6 and v7-8 in 156 human endometrium cancer specimens by means of
      immunohistochemistry. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were
      detected in 26% (41 out of 156), 31% (48 out of 156), 22% (35 out of 156) and 15%
      (23 out of 156) of the tumour samples respectively. The expression of CD44
      isoforms CD44v3, CD44v5 and CD44v7-8 showed no prognostic impact. In the
      univariate analysis, the expression of CD44v6 showed an association with
      shortened overall survival (log-rank test, P = 0.06). Multivariate analysis
      correcting for the confounding variable histological grading revealed CD44v6 not
      to be a prognostic factor in endometrial cancer (log-rank test, P = 0.06).
      Comparing the expression of CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 in
      45 specimens of normal endometrial tissue, we found an up-regulation of all
      investigated CD44 isoforms in the secretory phase compared with the proliferative
      phase of the menstrual cycle. Our data indicate that the expression of CD44
      isoforms, while obviously playing a role in the functional changes of normal
      endometrium, is not an adverse predictive factor in endometrial cancer.

PMID- 9569052
TI  - Independent prognostic importance of microvessel density in endometrial
      carcinoma.
AB  - Angiogenesis is thought to be an important factor for tumour growth and
      metastatic spread, and microvessel counts may provide useful prognostic
      information for several tumour types. To investigate the prognostic impact of
      angiogenesis in endometrial carcinoma patients, the intratumour microvessel
      density, which was determined immunohistochemically, has been related to
      survival. Sixty patients with endometrial carcinoma with long (median 19 years)
      and complete follow-up have been studied. Patients with increased mean
      microvessel density (MVDmean > 68 mm2) had a significantly shorter 5-year
      survival compared with the rest (57% vs 90%, P = 0.004). In multivariate survival
      analyses, MVDmean had an independent prognostic impact (P = 0.03) when FIGO
      stage, histological type, histological grade as well as nuclear p53 protein
      expression was adjusted for. These findings indicate that intratumour microvessel
      density may contribute additional prognostic information to that obtained from
      the known risk factors and may be helpful in identifying endometrial carcinoma
      patients at high risk for disease progression.

PMID- 9569053
TI  - Anthracycline doses in patients with liver dysfunction: do UK oncologists follow
      current recommendations?
AB  - The question of whether UK oncologists follow current anthracycline dose
      modifications when treating patients with liver dysfunction was addressed through
      a questionnaire. Oncologists were asked the dose of doxorubicin or epirubicin
      they would prescribe for a woman with breast cancer and liver metastases who had
      one of four different patterns of abnormal liver chemistry. In each case, the
      median dose of anthracycline that would have been prescribed was close to that
      currently recommended. There was, however, wide variation in the dose that
      oncologists said they would prescribe, some avoiding an anthracycline altogether,
      whereas others would give full-dose treatment. Medical oncologists would
      prescribe a significantly lower dose of anthracycline than clinical oncologists
      for a patient with the most severely disturbed liver tests. Overall, medical
      oncologists were also significantly more likely to prescribe epirubicin. These
      results show the need for new, widely accepted anthracycline dose modifications
      for patients with liver dysfunction.

PMID- 9569054
TI  - FEP regimen (epidoxorubicin, etoposide and cisplatin) in advanced gastric cancer,
      with or without low-dose GM-CSF: an Italian Trial in Medical Oncology (ITMO)
      study.
AB  - The new regimens developed over the last few years have led to an improvement in
      the treatment of advanced gastric cancer, and our previous experience confirmed
      the fact that the combination of etoposide, doxorubicin and cisplatin (EAP
      regimen) is an active treatment that leads to interesting complete remission
      rates. The primary end point of the present multicentre, randomized, parallel
      group phase II study was to determine the activity of the simplified 2-day EAP
      schedule in patients with locally advanced or metastatic gastric cancer, and to
      verify whether the addition of low doses of granulocyte-macrophage colony
      stimulating factor (GM-CSF) made it possible to increase dose intensity. Of the
      62 enrolled patients, 30 were randomized to receive epirubicin 35 mg m(-2),
      etoposide 120 mg m(-2) and cisplatin 45 mg m(-2) (FEP) on days 1 and 2 every 28
      days and 32 to receive the same schedule plus subcutaneous GM-CSF (molgramostin)
      150 microg day(-1) on days 5-14 every 21 days. The patients were stratified by
      age and the number of disease sites. The characteristics of the patients were
      well balanced between the two groups. The objective response rate of the patients
      as a whole was 34% (21 out of 62; 95% confidence interval 22-46), with only one
      complete remission. The median response duration was 4.5 months (range 1-24
      months). The median time to treatment failure was 5 months (range 1-14 months),
      without any difference between the two groups. The median survival of the
      patients as a whole was 9 months. Full doses were administered in 92% and 94% of
      the cycles in the control and GM-CSF arms respectively. The average dose
      intensity calculated for all drugs was 0.96% in the control and 1.27% in the GM
      CSF group. CTC-NCI grade 3-4 neutropenia was reported in 39% vs 45% of patients,
      thrombocytopenia in 11% vs 35% (P = 0.020) and anaemia in 7% vs 35% (P = 0.014).
      The FEP combination is as active (OR: 34%) in the treatment of patients with
      advanced gastric cancer as the EAP regimen, although it leads to fewer complete
      remissions. The patients randomized to receive low-dose GM-CSF achieved a
      significantly higher dose intensity than controls (P = 0.0001).

PMID- 9569055
TI  - Phase II trial of dexverapamil and epirubicin in patients with non-responsive
      metastatic breast cancer.
AB  - Agents capable of reversing P-glycoprotein-associated multidrug resistance have
      usually failed to enhance chemotherapy activity in patients with solid tumours.
      Based on its toxicity profile and experimental potency, dexverapamil, the R
      enantiomer of verapamil, is considered to be promising for clinical use as a
      chemosensitizer. The purpose of this early phase II trial was to evaluate the
      effects of dexverapamil on epirubicin toxicity, activity and pharmacokinetics in
      patients with metastatic breast cancer. A two-stage design was applied. Patients
      first received epirubicin alone at 120 mg m(-2) i.v. over 15 min, repeated every
      21 days. Patients with refractory disease continued to receive epirubicin at the
      same dose and schedule but supplemented with oral dexverapamil 300 mg every 6 h x
      13 doses. The Gehan design was applied to the dexverapamil/epirubicin cohort of
      patients. Thirty-nine patients were entered on study, 25 proceeded to receive
      epirubicin plus dexverapamil. Dexverapamil did not increase epirubicin toxicity.
      The dose intensity of epirubicin was similar when used alone or with
      dexverapamil. In nine intrapatient comparisons, the area under the plasma
      concentration-time curve (AUC) of epirubicin was significantly reduced by
      dexverapamil (mean 2968 vs 1901 microg ml[-1] h[-1], P= 0.02). The mean trough
      plasma levels of dexverapamil and its major metabolite nor-dexverapamil were 1.2
      and 1.5 microM respectively. The addition of dexverapamil to epirubicin induced
      partial responses in 4 of 23 patients evaluable for tumour response (17%, CI 5
      39%, s.e.P 0.079). The remissions lasted 3, 8, 11 and 11+ months. These data
      suggest that the concept of enhancing chemotherapy activity by adding
      chemosensitizers may function not only in haematological malignancies but also in
      selected solid tumours. An increase in the AUC and toxicity of cytotoxic agents
      does not seem to be a prerequisite for chemosensitizers to enhance anti-tumour
      activity.

PMID- 9569056
TI  - NM23-H1 immunostaining is inversely associated with tumour staging but not
      overall survival or disease recurrence in colorectal carcinomas.
AB  - The NM23-H1 gene product has been recently identified as a potential metastasis
      suppressor. Studies on breast carcinomas have shown an inverse correlation
      between NM23-H1 status and stage of carcinogenesis and overall survival. However,
      in colorectal cancer, conflicting data have been reported. This study aimed to
      investigate whether NM23-H1 immunostaining is correlated with tumour stage,
      overall survival, disease recurrence, tumour differentiation, age and sex in
      colorectal carcinomas for the Singapore population using chi-square analysis. The
      staining was performed on 141 paraffin-embedded surgical specimens collected
      between 1991 and 1992 using a monoclonal anti-NM23-H1 antibody. Follow-up of
      patients was until time of death or for 5 years. There was a very significant
      inverse association between tumour staging and NM23-H1 status (P = 0.0004).
      However, NM23-H1 expression was not significantly correlated to overall 5-year
      survival, disease recurrence, tumour differentiation, age or sex. Thus, although
      NM23-H1 may be involved in suppressing metastasis, NM23-H1 immunohistochemistry
      has no prognostic value in colorectal cancer. This is the first report of a
      significant inverse association of NM23-H1 status with tumour staging in
      colorectal cancer which showed no correlation with overall survival or disease
      recurrence. Our result thus cautions against the practice of equating an inverse
      relation of genetic markers with tumour staging to survival or disease
      recurrence.

PMID- 9569057
TI  - Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates
      with lymph node status and angiogenesis.
AB  - Human AP endonuclease (HAP1) plays a major role in the repair of
      apurinic/apyrimidinic (AP) sites in cellular DNA. We used immunohistochemistry to
      examine the expression of HAP1 in normal breast and in 102 primary breast
      carcinomas. In normal breast epithelium, HAP1 had a uniformly nuclear
      localization. However, in lactating glandular epithelium, the expression of HAP1
      was predominantly cytoplasmic. In carcinomas, both nuclear and cytoplasmic (44%),
      cytoplasmic (28%) or nuclear staining (24%) were observed. In four cases (4%), no
      HAP1 expression was detected. All patterns of expression for HAP1 were
      demonstrated for ductal carcinomas in situ (DCIS), although comedo-type DCIS were
      usually accompanied by mostly cytoplasmic staining. Similarly, the HAP1
      expression in regions of invasive tumour necrosis was cytoplasmic. Pure nuclear
      HAP1 expression was significantly correlated with low angiogenesis (P = 0.007)
      and negative lymph node status (P = 0.001). In contrast, cases with cytoplasmic
      as well as nuclear staining were associated with poor prognostic factors, such as
      high angiogenesis (P = 0.03) and node positivity (P = 0.03). The pure nuclear
      staining may be related to better differentiation, as in normal breast, and hence
      better prognostic features, and cytoplasmic staining to a more metabolically
      active phenotype with high protein synthesis, as in lactating breast.

PMID- 9569058
TI  - Seasonal variations in the presentation and growth of thyroid cancer.
AB  - Seasonal variation has been described in the presentation and growth of several
      malignant tumours, including cancers of the breast, uterus, uterine cervix,
      urinary bladder, liver, lymphatic system and skin, although the mechanisms are
      not known. We herein describe a circannual rhythm for thyroid cancer (total =
      2627), with significantly more cases presenting during the late autumn and
      winter. In a subset of these cases (127 papillary carcinomas), significant
      seasonal variations with highest values in autumn-winter were found for tumour
      diameter and proliferation indicators (S- and G2M-phase fractions). These results
      indicate the likelihood of a seasonal factor (or factors) of importance for the
      regulation and modification of tumour cell proliferation. When further clarified,
      this might be of relevance for the planning of diagnostic and therapeutic
      strategies.

PMID- 9569059
TI  - Testicular cancer risk and maternal parity: a population-based cohort study.
AB  - The aim was to study, in a population-based cohort design, whether first-born
      sons run a higher risk of testicular cancer than later born sons; to investigate
      whether this difference in risk was affected by birth cohort, age of the son,
      maternal age, interval to previous delivery and other reproductive factors; and,
      finally, to evaluate to what extent changes in women's parity over time might
      explain the increasing incidence of testicular cancer. By using data from the
      Civil Registration System, a database was established of all women born in
      Denmark since 1935 and all their children alive in 1968 or born later. Sons with
      testicular cancer were identified in the Danish Cancer Registry. Among 1015994
      sons followed for 15981 967 person-years, 626 developed testicular cancer (443
      non-seminomas, 183 seminomas). Later born sons had a decreased risk of testicular
      cancer (RR = 0.80, 95% CI = 0.67-0.95) compared with first-born sons. The RR was
      0.79 (95% CI = 0.64-0.98) for non-seminomas and 0.81 (95% CI = 0.58-1.13) for
      seminomas. There was no association between testicular cancer risk and overall
      parity of the mother, maternal or paternal age at the birth of the son, or
      maternal age at first birth. The decreased risk of testicular cancer among later
      born sons was not modified by age, birth cohort, interval to the previous birth,
      sex of the first-born child, or maternal age at birth of the son or at first
      birth. The increased proportion of first-borns from birth cohort 1946 to birth
      cohort 1969 only explained around 3% of an approximated two-fold increase in
      incidence between the cohorts. Our data document a distinctly higher risk of
      testicular cancer in first-born compared with later born sons and suggest that
      the most likely explanation should be sought among exposures in utero. The
      increase in the proportion of first-borns in the population has only contributed
      marginally to the increase in testicular cancer incidence.

PMID- 9569060
TI  - Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt.
AB  - The relationship between history of schistosomiasis and bladder cancer risk was
      investigated using data from a case-control study conducted between January 1994
      and July 1996 in Alexandria, Egypt. Cases were 190 subjects with incident,
      histologically confirmed invasive cancer of the bladder, and controls were 187
      subjects admitted to hospital for acute, non-neoplastic, non-urinary tract
      conditions. Eighty-six cases (45%) vs 69 controls (37%) reported a history of
      urinary schistosomiasis. The corresponding multivariate odds ratio (OR) of
      bladder cancer -- after allowance for age, sex, education, smoking, other urinary
      infections and high-risk occupations -- was 1.72 (95% confidence interval (CI)
      1.0-2.9). The ORs were 0.22 (95% CI 0.1-0.4) for intestinal schistosomiasis and
      0.32 (95% CI 0.1-1.9) for schistosomiasis of other types. The OR for urinary
      schistosomiasis was higher in subjects who were younger at first diagnosis (OR of
      3.3 for <15 years) and in those with a long time since first diagnosis (OR of 3.0
      for > or = 35 years). The ORs were 15.8 for male ever-smokers with a history of
      urinary schistosomiasis, compared with never-smokers without such a history, and
      3.2 for men ever-infected with urinary Schistosoma haematobium and ever-employed
      in high-risk occupations, compared with those never-infected and with no high
      risk occupational history. This study confirms that clinical history of urinary
      schistosomiasis is significantly, but modestly, associated with increased bladder
      cancer risk, explaining some 16% of bladder cancer cases in this Egyptian
      population.

PMID- 9569061
TI  - High incidence of classical Kaposi's sarcoma in Iceland and the Faroe Islands.
AB  - We have examined the incidence of non-AIDS-related Kaposi's sarcoma in Iceland
      (1955-79) and the Faroe Islands (1974-95). In Iceland, 19 cases, nine in men and
      ten in women, were identified, and in the Faroe Islands four cases in men and
      three cases in women were found. This corresponded to surprisingly high incidence
      rates. In men, world standardized rates (per 100000 person-years) were 0.4 and
      0.6 in Iceland and the Faroe Islands, respectively, and for women, the figures
      were 0.3 (Iceland) and 0.5 (the Faroe Islands). These are among the highest rates
      ever reported. No explanation for the high rates of Kaposi's sarcoma in these two
      North Atlantic communities could be identified.

PMID- 9569063
TI  - The Human Genome Project.

PMID- 9569062
TI  - High suicide mortality soon after diagnosis among cancer patients in central
      Italy.
AB  - A high suicide mortality risk has been documented among a population-based cohort
      of 27 123 cancer patients resident in central Italy where the general suicide
      rate is low. Forty-one suicides were observed (SMR = 2.36) which were only 0.2%
      of all deaths. However, the highest risk (SMR = 27.7) during the first 6 months
      after diagnosis, represents a greater contrast with the general population than
      has been observed in other studies.

PMID- 9569064
TI  - Joint physiology: relevant to the rheumatologist?

PMID- 9569065
TI  - Rheumatoid arthritis: the predictable effect of small immune complexes in which
      antibody is also antigen.

PMID- 9569066
TI  - Hypothalamic-pituitary-mediated immunomodulation: arginine vasopressin is a
      neuroendocrine immune mediator.
AB  - Organisms respond to a variety of environmental agents, such as those that cause
      inflammation, by mounting a coordinated complex series of adaptive responses
      involving the immune, nervous and endocrine systems. These adaptations are aimed
      at restoring the homeostatic balance and the return to the status quo ante. This
      interaction is facilitated by cytokines, hormones and neurotransmitters, as well
      as receptors that are endogenous to the neural, immune and endocrine systems.
      These shared ligands and receptors provide the molecular basis of this cross
      talk. Studies of animal models of autoimmune diseases have shown that defects in
      the neuroendocrine immune communications contribute to the development of chronic
      inflammatory autoimmune disease. By analogy, similar observations have now been
      made in patients with inflammatory rheumatic disorders. For instance, patients
      with rheumatoid arthritis have abnormally low cortisol responses to inflammation,
      whilst the production of prolactin is excessive and dysregulated. Prolactin is a
      pro-inflammatory neuropeptide. This paper reviews the evidence to support the
      viewpoint that the neuropeptide arginine vasopressin, which is also produced by
      the hypothalamus, should be considered to be another neuroendocrine modulator of
      immune and inflammatory responses. It is also being hypothesized that the
      production of arginine vasopressin might be dysregulated and excessive in
      rheumatoid arthritis, and that this could be another additional neuroendocrine
      factor contributing to the pathophysiology of the disease.

PMID- 9569067
TI  - Enzymatic identification of the load-bearing boundary lubricant in the joint.
AB  - Bovine articular cartilage and synovial fluid (SF) were co-incubated with one of
      three enzymes selected to destroy each of the three major contenders for the
      active ingredient imparting such remarkable load-bearing lubrication to the
      normal joint. Destroying hyaluronic acid (HA), alias hyaluronan, with
      hyaluronidase, both frictional and wear tests displayed no significant change in
      accordance with most previous studies of SF alone. Destroying surface-active
      phospholipid (SAPL) with phospholipase A2, there was a highly significant dose
      dependent compromise of lubrication as recorded on both tests. Trypsin produced a
      somewhat surprising result in that lubrication of the cartilage actually
      improved. This result can be interpreted as indicating that lubricin is not the
      lubricant per se, but, as a water-soluble, macromolecular, proteinaceous carrier
      for phospholipid, its destruction caused more SAPL to be deposited as the true
      load-bearing lubricant. These results are discussed in the context that SAPL,
      lubricin and HA each have specific roles in a comprehensive lubrication system.

PMID- 9569068
TI  - Deficiency of lubricating surfactant lining the articular surfaces of replaced
      hips and knees.
AB  - While preceding papers have demonstrated that the active load-bearing agent in
      the boundary mode of joint lubrication is surface-active phospholipid (SAPL)-
      probably adsorbed as the outermost layer of articular cartilage--this study is
      designed to determine whether that layer is deficient in osteoarthritis (OA).
      This layer has been studied on 12 hips and 31 knees obtained from surgically
      replaced joints afflicted with OA. Measurement of the contact angle (theta)
      subtended by a droplet of saline clearly demonstrated a highly significant
      decrease in hydrophobicity, theta falling from 100 degrees for 13 bovine controls
      (78 degrees for five human controls) to 56 degrees for arthritic hips and 63
      degrees and 68 degrees for the 'worn' and 'unworn' areas of arthritic knees,
      respectively. These changes were reflected in the quantities of SAPL (and
      proteolipid) recovered from the same articular surfaces by solvent rinsing,
      yields of SAPL being 36% lower in hips and 25% lower in 'worn' areas of knees,
      but not significantly different in 'unworn' areas. These results indicate that
      the outermost lubricating layer of SAPL deposited onto articular cartilage from
      SF is deficient in OA.

PMID- 9569070
TI  - A comparison of two recently developed health status instruments for patients
      with arthritis: Dutch-AIMS2 and IRGL. Arthritis Impact Measurement Scales. Impact
      of Rheumatic diseases on General health and Lifestyle.
AB  - Two multidimensional health status instruments of rheumatic diseases, the Dutch
      AIMS2 and the IRGL (Impact of Rheumatic diseases on General health and
      Lifestyle), were compared in a sample of 284 rheumatoid arthritis patients with
      regard to their measurement properties and usefulness for research purposes. Both
      questionnaires showed an excellent reliability (Cronbach's alpha), and were
      highly comparable with regard to their construct and convergent validity. Second
      order factor analysis confirmed the physical, psychological and social health
      dimensions for both questionnaires. The comparability between the instruments was
      established by high intercorrelations between the physical and psychological
      health dimensions. Sufficient convergent validity was indicated by the strong
      correlations between the physical functioning scales and clinical and laboratory
      measures. The main differences between both questionnaires relate to their length
      and emphasis on health aspects. The Dutch-AIMS2 is characterized by a more
      extensive assessment of the physical dimension and the additional measurement of
      general health aspects. The shorter IRGL exclusively assesses the main health
      dimensions with a more comprehensive measurement of the psychological and social
      dimensions. The instrument that reflects the subject in question most adequately
      should be chosen.

PMID- 9569069
TI  - Co-culture of synovial fibroblasts and differentiated U937 cells is sufficient
      for high interleukin-6 but not interleukin-1beta or tumour necrosis factor-alpha
      release.
AB  - Inflamed synovium is characterized by high concentrations of cytokines
      [interleukin (IL)-6, IL-1beta and tumour necrosis factor (TNF)-alpha] and the
      abundant presence of infiltrated monocytes, many of which are found adjacent to
      the resident fibroblast-like synoviocytes. We have used a co-culture of
      fibroblast-like synoviocytes and differentiated U937 cells to study IL-6, IL
      1beta and TNF-alpha release. After a 3 day co-culture, 35% of the U937 cells had
      adhered and were fully differentiated towards monocytes, as determined by
      expression of p47phox, CD14, MSE-1, Mac-1, collagenase and NADPH oxidase
      activity. IL-6 release from fibroblast-like synoviocytes was induced 4-fold by co
      culture with differentiated U937 cells. However, co-culture of differentiated
      U937 cells with fibroblast-like synoviocytes failed to release detectable levels
      of IL-1beta and TNF-alpha from the U937 cells. Addition of synovial fluid further
      increased IL-6 release, but again had no effect on IL-1beta or TNF-alpha,
      although U937 cells differentiated by phorbol ester were able to release these
      two cytokines and, in the case of the co-culture, mRNAs for both cytokines were
      highly expressed in the U937 cells. We postulate that the influx of monocytes
      into the synovium is instrumental in the elevation of IL-6 levels, but this is
      not sufficient to explain high levels of IL-1beta or TNF-alpha.

PMID- 9569071
TI  - HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy:
      correlation with disease severity.
AB  - The aim of the study was to evaluate the relationship between the presence of the
      'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles,
      rheumatoid factor and disease severity in Northern Italian patients with
      rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA
      patients were studied. Each DR4-positive patient was matched with two DR4
      negative controls of similar disease duration and sex. HLA-DRB1 alleles were
      determined in the 86 patients and 351 controls from the same geographical area.
      The patients were retrospectively evaluated for extra-articular features (EAF)
      and radiographic damage. The rheumatoid epitope was expressed in 45% of patients.
      No significant differences in the presence of rheumatoid factor, EAF and
      articular damage were observed between patients with no, one or two doses of
      epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a
      higher number of eroded joints and a higher Larsen score compared to those
      without the epitope. No differences were present between patients expressing HLA
      DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of
      expression of the rheumatoid epitope, seropositive patients had more EAF and more
      erosive disease compared to those who were seronegative. Even if most Northern
      Italian RA patients do not express the rheumatoid epitope, the radiological
      severity of disease is associated with HLA-DRB1*04 alleles.

PMID- 9569072
TI  - Synovial lining, endothelial and inflammatory mononuclear cell proliferation in
      synovial membranes in psoriatic and reactive arthritis: a comparative
      quantitative morphometric study.
AB  - The extent of synovial cell proliferation in situ and its relationship to the
      destructive potential of rheumatoid arthritis (RA) is a matter of continuing
      debate. Notably, the situation has not been elucidated in other inflammatory
      arthritides [i.e. reactive (ReA) and psoriatic (PsA)], which, although they share
      some histopathological similarities with RA, develop different patterns of joint
      involvement. In order to estimate the proliferation of synovial cells in situ in
      PsA and ReA, and to compare this with RA and with 'non-inflammatory' joint
      lesions, we have utilized immunostaining of the Ki-67 antigen complemented with
      Ki-67/CD68 or Ki-67/leucocyte common antigen (LCA, clones 2B11 and PD7/26) double
      stainings to assess the extent of mononuclear inflammatory cell proliferation.
      Synovial samples analysed were from 33 patients: RA (n = 8), PsA (n = 13), ReA (n
      = 6) and six 'non-inflammatory controls' (degenerative or traumatic joint
      lesions). Thickening of the synovial lining (in particular in RA) and
      perivascular accumulations of mononuclear inflammatory cells, predominantly
      lymphocytes, were characteristic features in all synovitides. In contrast to the
      thickened avascular synovial lining in RA, in 5/13 cases with PsA, blood vessels
      were observed in the lining. The percentage of lining cells expressing Ki-67
      antigen was higher in RA (median = 4.7, interquartile range [Q3-Q1] = 3.9, mean
      [95% CI] = 3.5 [1.7-5.2], P = 0.0063), PsA (median = 1.2, [Q3-Q1] = 1.9, mean
      [95% CI] = 1.6 [0.7-2.5], P = 0.007) and ReA (median = 1.4, [Q3-Q1] = 2.3, mean
      [95% CI] = 1.6 [0.1-3.1], P = 0.0235) than in controls (median = 0.1, [Q3-Q1] =
      0.45, mean [95% CI] = 0.2 [0.07-0.5]). In this respect, the differences between
      different forms of the inflammatory arthritides were not statistically
      significant (P > 0.05). In RA, PsA and ReA, the percentage of labelled cells in
      the inflammatory mononuclear cell-rich areas was higher than in controls. The
      percentage of proliferating endothelial cells was also significantly higher in
      RA, PsA and ReA than in controls. However, in RA, endothelial expression of Ki-67
      antigen was often seen in small blood vessels, whereas in PsA, Ki-67 antigen was
      preferably expressed in the medium to large blood vessels. Synovial lining cells
      of the monocyte/macrophage lineage (type A synoviocytes), but not stromal
      monocytes, demonstrated modest proliferation in situ. These results indicate that
      although proliferation of synovial lining fibroblasts is a prominent feature in
      RA, the extents to which this, or in situ proliferation of lymphocytes,
      contribute to the histopathology of PsA, ReA and RA are comparable. Vascular
      involvement is suggested by the proliferation of endothelial cells in RA, PsA and
      ReA in an overlapping manner, but, based on topological differences, such a
      response may represent diverse pathological features, such as angiogenesis,
      vascular enlargement and reparative responses to injury.

PMID- 9569073
TI  - Analysis of the T-cell receptor Valpha repertoire and cytokine gene expression in
      Sjogren's syndrome.
AB  - The antigen receptor diversity of pathogenic T cells in Sjogren's syndrome (SS)
      may have important implications in the development of the disease; cytokines from
      these cells and other sources also play a role in the pathogenesis of this
      disease. Using a semi-quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) technique, we have attempted to correlate the presence of
      restriction in the T-cell receptor (TCR) repertoire with cytokine profiles. We
      have analysed TCR V alpha family usage, and the expression of interleukin-1alpha
      (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma
      (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), in labial biopsies from
      12 patients with SS and compared these with samples from three patients with
      chronic sialadenitis (CS). Only one of the SS biopsies showed evidence of V alpha
      restriction (three out of 18 gene families). Apart from this, expression patterns
      were similar in both patient groups. Four of the 12 SS samples demonstrated a
      'limited heterogeneity' of the V alpha repertoire with 3-4 families predominantly
      expressed, in particular V alpha1 and V alpha3. Peripheral blood lymphocytes were
      unrestricted. The cytokine profiles of the SS and CS biopsies were generally
      similar. However both IFN-gamma and IL-1alpha were absent from CS, but present in
      SS samples. The expression of IFN-gamma in the majority of the samples, together
      with a lack of IL-4 and IL-13 mRNA, suggests the predominance of a Th1 response
      in SS. There was no clear association between the repertoire of V alpha genes
      expressed and the cytokine profile observed. However, the V alpha restriction in
      one SS sample did correspond with a limited diversity of cytokines detected.

PMID- 9569074
TI  - Absence of an association between mannose-binding lectin polymorphism and
      rheumatoid arthritis.
AB  - It has been proposed that mannose-binding lectin (MBL) interactions with
      agalactosyl forms of IgG immunoglobulins found in rheumatoid synovial fluid might
      lead to enhanced complement activation, an important mediator of the joint damage
      in rheumatoid arthritis (RA). In order to investigate this possible link between
      increased MBL-mediated activation of complement and perpetuation of rheumatoid
      synovitis, we have compared the frequency of an allelic form of MBL, known to be
      incapable of activating complement, in a group of hospital patients with severe
      RA and control subjects. No evidence was found to support an association between
      the presence of this MBL allele and protection from rheumatoid disease; genotype
      frequencies were similar in both groups. This suggests that complement activation
      via MBL-agalactosyl IgG complexes is unlikely to play a major role in the
      pathophysiology of RA.

PMID- 9569075
TI  - An initially double-blind controlled 96 week trial of depot methylprednisolone
      against oral prednisolone in the treatment of polymyalgia rheumatica.
AB  - The objective was to compare the efficacy and safety of intramuscular
      methylprednisolone acetate (i.m. MP) with oral prednisolone (OP) in the treatment
      of polymyalgia rheumatica (PMR), a common steroid-treated illness where prolonged
      therapy can lead to steroid side-effects. The cumulative dose with i.m. MP
      injections given every 3-4 weeks is considerably smaller than that with
      conventional OP, and may therefore be associated with fewer long-term side
      effects. A hybrid design was used with an initial 12 week double-blind placebo
      controlled phase followed by an open phase on active treatment up to 96 weeks.
      The study was multicentre hospital out-patient based and included 60 patients
      with untreated PMR. In the double-blind phase, either 120 mg 3-weekly i.m. MP or
      gradually tapering daily OP (initial dose 15 mg) were administered. In the open
      phase, subjects continued their active treatment with gradual tapering of the
      steroid dosage. The remission rate at 12, 48 and 96 weeks, and other measures of
      disease activity, i.e. sedimentation rate, pain and morning stiffness, and
      percentage of adverse reactions and serious complications such as fractures, were
      the main outcome measures. Sixty patients entered (30 OP:30 i.m. MP) and 49 (25
      OP:24 i.m. MP) completed the study. There were similar remission rates after the
      double-blind phase (60.6% OP and 66.6% i.m. MP, respectively) and similar disease
      control in the succeeding open phase. With steroid tapering, the mean erythrocyte
      sedimentation rate for the entire cohort registered a significant increase in the
      absence of an increase in symptoms. At 96 weeks, the cumulative mean steroid dose
      in subjects treated with i.m. MP was equivalent to 56% that of subjects treated
      with OP. There were eight fractures with OP compared to one on i.m. MP. Mean
      weight gain was significantly greater with OP than i.m. MP (3.42 vs 0.82 kg, P <
      0.005). Minor adverse reactions were similar in both groups apart from slightly
      increased bruising with i.m. MP. Only patients on OP reported moon face,
      hypertension, cataracts, back pain and depression, but the numbers were small. It
      is possible to achieve equivalent long-term disease control in PMR with i.m. MP
      compared to OP. I.m. MP was associated with far fewer fractures and lesser weight
      gain, presumably related to lower cumulative dose. These findings may have
      implications in the steroid treatment of PMR, and other rheumatic and non
      rheumatic diseases.

PMID- 9569076
TI  - Improvement of physical fitness and muscle strength in
      polymyositis/dermatomyositis patients by a training programme.
AB  - In the present investigation, the benefit of physical training in patients with
      inflammatory myopathy was studied. In this prospective, randomized, controlled
      study, 14 patients with polymyositis (PM) or dermatomyositis (DM) were
      investigated. The training, consisting of bicycle exercise and step aerobics,
      took place over a 6 week period. Baseline and endpoint measurements included an
      'activities of daily living' (ADL) score, peak isometric torque (PIT) generated
      by muscle groups in the lower extremities, peak oxygen consumption (VO2max), and
      creatine phosphokinase (CPK) levels. There was no significant rise in disease
      activity in the training group in comparison to the controls. The ADL score for
      the treatment group, in comparison to the control group, improved (P < 0.02), PIT
      rose (P < 0.05) and there was a statistically significant increase in oxygen
      uptake relative to body weight (P < 0.05). No rise in inflammatory activity, but
      significant improvement in muscle strength, oxygen uptake and well-being, were
      found in patients with inflammatory myopathy as a result of physical training.
      Besides medication, a physical training programme consisting mainly of concentric
      muscle contractions should therefore be an integral part of therapy, particularly
      in view of the cardiopulmonary risk of these patients.

PMID- 9569077
TI  - HLA associations in three mutually exclusive autoantibody subgroups in UK
      systemic sclerosis patients.
AB  - Systemic sclerosis (SSc) is characterized by the presence of autoantibodies,
      mostly IgG, which target a limited set of nuclear proteins. These antinuclear
      antibodies (ANA) associate with disease subgroups and specific organ involvement.
      Here we show that there is mutual exclusivity of individual ANA in 130 UK SSc
      patients, confirm clinical associations with antibody profile and extend the
      analysis to include genetic data. The ANA mutual exclusivity observed leads to
      the possibility that SSc, in these patients, is in fact three separate diseases.
      An alternative explanation for exclusivity relates to the fact that optimal
      production of IgG antibody requires T-cell help, a process restricted by the HLA
      class II presentation of antigen peptide. If each autoantibody has a different
      and tight MHC restriction, then there is a possibility that these groups arose
      from a common pathway and were modified by genetics into the mutually exclusive
      groups observed, making the separate disease theory less tenable. In order to
      answer this question, we have determined MHC class II restriction precisely using
      high-resolution HLA genotyping (SSP) coupled with an amino acid analysis program
      in our 130 UK SSc patients. DRB1*11 was associated with anti-topoisomerase-I
      antibody (ATA)-positive patients (P = 0.007) and when combined with ATA (RR =
      15.82), dcSSc (RR = 11.45), or both (RR = 21.9), represented the strongest risk
      factor for pulmonary fibrosis. Patients with antibodies to RNA polymerases I, II
      and III were associated with DQB1*0201. At the amino acid level, 20 positions in
      DRB1 and 20 positions in DQB1 showed some significant correlation with an ANA
      group. Clearly, however, the linkages to MHC class II alleles are not nearly
      strong enough to explain the mutually exclusive nature of the autoantibody groups
      and our results support, but do not prove, the separate disease theory.

PMID- 9569079
TI  - Recommendations for the registration of drugs used in the treatment of rheumatoid
      arthritis. Group for the Respect of Ethics and Excellence in Science (GREES):
      rheumatoid arthritis section.
AB  - Rheumatoid arthritis (RA) is the commonest form of chronic inflammatory joint
      disease and a major target for symptom-modifying and disease-modifying drug
      therapy. New approaches to the treatment of RA using biological agents targeted
      to cellular receptors, cytokines and other mediators of inflammation, together
      with the availability of new methods of outcome assessment, make it timely to
      reconsider the classification of anti-rheumatic drugs and the requirements for
      the registration of new drug entities. Under the auspices of GREES (Group for the
      Respect of Ethics and Excellence in Science), a European Working Group of
      clinicians with experience in rheumatology, scientists and representatives from
      industry and national drug licensing authorities have formulated recommendations
      for the requirements for registration of anti-rheumatic drugs designed for
      symptom modification, structural modification and the suppression of
      inflammation, with particular emphasis placed on quality of life assessment by
      generic and disease-specific validated methods. This paper outlines the group's
      advice for pre-clinical testing, and Phase I, Phase II and Phase III trials to
      allow licences to be granted for each indication, while recognizing that a single
      drug may have reason to be approved under several headings.

PMID- 9569078
TI  - Anticardiolipin antibodies in giant cell arteritis and polymyalgia rheumatica: a
      study of 40 cases.
AB  - The occurrence and clinical value of anticardiolipin antibodies (aCL) were
      studied in 33 patients with giant cell arteritis (GCA) and in seven patients with
      polymyalgia rheumatica (PMR), at onset and during follow-up. aCL were present in
      19/40 (47.5%) GCA/PMR cases, most of them of the IgG isotype, whereas all
      controls (21 subjects) were aCL negative. The presence of aCL was not associated
      with inflammatory parameters or clinical signs of arteritis; however, they
      disappeared in a significant percentage (56%) of patients during steroid therapy.
      No correlation was found between ischaemic events and aCL, suggesting that they
      are not important for the development of vascular complications in GCA/PMR
      patients. Moreover, a retrospective evaluation of our data showed a correlation
      between aCL positivity and anaemia, whose significance remains to be elucidated.

PMID- 9569080
TI  - Clinical efficacy of cyclosporin a neoral in the treatment of paediatric lupus
      nephritis with heavy proteinuria.
AB  - Cyclosporin A (CsA) was introduced in recent years for the treatment of lupus
      nephritis in patients with steroid resistance or in those with severe
      corticosteroid toxicity. Our previous study on paediatric patients showed that
      Neoral (a new microemulsion formulation) had better bioavailability than CsA
      capsules. To evaluate the clinical efficacy of Neoral in children with lupus
      nephritis compared with conventional therapy, we performed an open randomized
      study on 40 children, ranging from 9 to 14 yr old, with class III-V lupus
      nephritis and heavy proteinuria. They were randomly assigned to either Neoral (5
      mg/kg/day), administered q.12.h, or prednisolone (2 mg/kg/day) plus
      cyclophosphamide (2 mg/kg/day) for 1 yr. Both groups showed a significant
      decrease in proteinuria (Neoral: 4.62 +/- 1.93 to 0.35 +/- 0.29 g/day, P < 0.05;
      prednisolone plus cyclophosphamide: 4.52 +/- 1.86 to 0.62 +/- 0.21 g/day, P <
      0.01). The CH50 haemolytic assay titre decreased after 1 yr of Neoral treatment
      (26.5 +/- 0.9 to 21.4 +/- 2.2 U/ml, P < 0.05). Serum C3 and anti-double-stranded
      (ds) DNA antibody levels also fell with Neoral (C3: 86.2 +/- 6.8 to 76.3 +/- 4.5
      mg/dl; anti-ds DNA antibodies: 14.1 +/- 3.2 to 8.2 +/- 1.4 IU/ml, P < 0.05). The
      Neoral group had a significant increase in growth rate over the prednisolone plus
      cyclophosphamide group (8.2 +/- 1.1 cm/yr vs 2.7 +/- 0.6 cm/yr, P < 0.01) with
      improvement of growth status. During the study period, patients tolerated Neoral
      well with no significant changes in renal function, liver function or lipid
      profile. Our study implies that Neoral appears to be effective in suppressing
      proteinuria. Neoral should be regarded as being adjunctive therapy, perhaps with
      a steroid-sparing effect, in paediatric lupus nephritis. However, its long-term
      use awaits further studies.

PMID- 9569081
TI  - Atypical juvenile generalized scleroderma presenting as polyarthritis and failure
      to thrive.
AB  - In this Grand Round, two children are described with atypical generalized
      scleroderma and severe failure to thrive. Neither had Raynaud's phenomenon nor
      evidence of gastrointestinal (GI) disease. Treatment with non-steroidal anti
      inflammatory drugs, prednisone, D-penicillamine, alpha and gamma interferon was
      unsuccessful in reversing the sclerodermatous changes and growth arrest. Dietary
      intake analysis and extensive GI investigation were performed in both. In one
      case, resting energy expenditure (Ee) was repeatedly measured. His intake did not
      meet requirements for growth. Supplemental tube feeding (900 kcal in 6 h) was
      commenced, causing an increase in weight from 11 to 16 kg. The other patient
      refused supplementary tube feeding and no weight gain has been observed for 5 yr.
      In conclusion, early-onset generalized scleroderma in the absence of visceral
      involvement, but with growth failure, may represent an atypical form of systemic
      sclerosis. The response of the two patients to conventional therapy was
      disappointing. However, the rapid catch-up growth induced by tube feeding
      observed in one patient underlines the importance of adequate dietary management.

PMID- 9569082
TI  - Successful treatment of gangrene in systemic necrotizing vasculitis with
      iloprost.
AB  - Systemic necrotizing vasculitis is uncommon in children and may be rarely
      associated with gangrene. We describe a 3-yr-old girl with parvovirus B19-induced
      necrotizing vasculitis whose digital gangrene was successfully treated with
      iloprost, a prostacyclin analogue.

PMID- 9569083
TI  - Familial dermatomyositis.
AB  - A case of familial dermatomyositis (DM) is reported in a 27-yr-old mother and her
      daughter aged 2 yr and 8 months. Familial DM is a rare occurrence and has never
      been reported in a child of < 4 yr old, although isolated cases of DM have been
      found in infants as young as 1 yr. The mother responded readily to
      corticosteroids; however, the child proved resistant to steroids and was
      eventually successfully managed on a combination of methotrexate and
      prednisolone. Another daughter presented with the dermatological stigmata of DM,
      but with no evidence of muscle involvement.

PMID- 9569084
TI  - The expanding role of the nurse in rheumatology.

PMID- 9569085
TI  - Spondylo-epiphyseal dysplasia tarda with progressive arthropathy mimicking
      juvenile chronic arthritis.

PMID- 9569086
TI  - Therapy for psoriatic arthritis: sometimes a conflict for psoriasis.

PMID- 9569087
TI  - A case of calcific lateral epicondylitis: a histological and ultrastructural
      study.

PMID- 9569088
TI  - Cell surface characterization of amastigotes of Trypanosoma cruzi obtained from
      different sources.
AB  - The present study analyses the morphology and the exposition of surface
      carbohydrates and the Ssp4 antigen of amastigote forms of Trypanosoma cruzi (Y
      strain) obtained from three different sources: (a) intracellular, isolated from
      infected Vero cells 3 days after infection, (b) extracellular, isolated from the
      supernatant of Vero cells 15 days after infection, and (c) axenic, obtained by
      incubation of tissue culture trypomastigotes in LIT medium, at 37 degrees C for 4
      days. No morphological differences were observed by light microscopy among these
      amastigotes. Transmission electron microscopy of thin sections showed a thick
      cell coat easily observed on the plasma membrane of axenic amastigotes.
      Carbohydrate-containing sites on the surface of the three different amastigotes
      were analysed using lectins, agglutination assays and flow cytometry. Mannose
      and/or glucose residues were found on the surface of all populations, but
      intracellular amastigotes showed the highest number. A small group of cells from
      the different populations expressed galactose and N-acetyl-glucosamine residues.
      The presence and distribution of the Ssp4 antigen in the different amastigote
      populations were evaluated using FITC and gold-labelled antibodies, and observed
      with an electronic programmable individual cell sorter and transmission electron
      microscopy. Ssp4 antigen was present on the membrane lining the flagellar pocket
      and on the cell surface, as well as inside the cytoplasmic vesicles of the host
      cell. Flow cytometry analysis of different amastigote populations showed that
      intracellular amastigotes presented the highest percentage of Ssp4-expressing
      cells.

PMID- 9569089
TI  - Trichinella spiralis, T. britovi, and T. nativa: infectivity, larval distribution
      in muscle, and antibody response after experimental infection of pigs.
AB  - The infectivity of Trichinella spiralis, T. nativa, and T. britovi was
      experimentally compared in pigs. Blood sampling was performed weekly, and muscle
      juices were obtained at slaughter 10 weeks after inoculation. Muscle larvae were
      found in all of four pigs inoculated with T. spiralis [mean 190 larvae per gram
      (lpg)] and in three of four pigs inoculated with T. britovi (mean 7 lpg). No
      larvae were found in pigs inoculated with T. nativa. For T. spiralis and T.
      britovi, the neck muscle (m. splenius) appears to be a predilection site in
      addition to the tongue, the diaphragm, and the jaw. High antibody responses were
      found in all experimental groups, independent of the antigen used, and even in
      pigs in which no muscle larvae were recovered. The strong and consistent antibody
      response found with meat juice indicates the usefulness of this material where a
      blood sample is not obtainable, e.g. meat samples from wild animals.
      Immunoblotting (Western blots) on slaughter sera revealed no species specificity
      when comparing homologous versus heterologous staining.

PMID- 9569090
TI  - Eimeria tenella: two species of extrachromosomal DNA revealed by pulsed-field gel
      electrophoresis.

PMID- 9569091
TI  - Adhesion molecules in intestinal Schistosoma mansoni infection.
AB  - Adhesion molecules constitute essential elements in inflammation, mediating
      various cellular interactions. We investigated the expression of adhesion
      molecules mediating cell-cell [intercellular adhesion molecule-1 (ICAM-1) and
      lymphocyte function-associated antigen-1 (LFA-1)] and cell-matrix interactions
      [very late antigen-4 (VLA-4), VLA-6, and syndecan-1] in intestinal granulomas of
      mice infected with the parasite Schistosoma mansoni. Up-regulation of ICAM-1, LFA
      1, and VLA-4 was seen in ileal and colonic granulomas, at both the acute (8 weeks
      postinfection) and the chronic stage (13-16 weeks postinfection). Up-regulation
      of VLA-6 was absent in all intestinal granulomas. Syndecan-1 immunoreactive
      (antigen-driven) B-lymphocytes were seen in the proximity of egg-antigen-laden
      macrophages in the inner part of ileal and colonic granulomas, although B-cells
      are considered to be absent in ileal granulomas. Estimation of intestinal
      granuloma volumes demonstrated the lack of down-modulation observed in ileal
      granulomas. From our results we infer that adhesion molecules constitute
      important elements in schistosomal intestinal granuloma formation. Organ-related
      differences between hepatic and intestinal granulomas exist (e.g., granuloma
      volume), but these differences are not morphologically reflected in a
      differential expression of the adhesion molecules ICAM-1, LFA-1, and VLA-4.
      Syndecan-1 immunoreactive B-lymphocytes also appear to be involved in ileal
      granuloma formation.

PMID- 9569092
TI  - Distribution of whaleworm (Anisakis simplex, Nematoda, Ascaridoidea) L3 larvae in
      three species of marine fish; saithe (Pollachius virens (L.)), cod (Gadus morhua
      L.) and redfish (Sebastes marinus (L.)) from Norwegian waters.
AB  - The frequency distribution of Anisakis simplex L3 larvae between host tissues was
      investigated in three host species: saithe, cod and redfish. Fish were sampled
      from Norwegian coastal waters and examined for the presence of A. simplex in
      muscle and viscera. In all three of the host species, A. simplex larvae were most
      frequently detected in the viscera; the percentages of total infection for
      saithe, cod and redfish were 99.6%, 97.8% and 88.0%, respectively. In general,
      the distribution patterns of A. simplex L3 between muscle and viscera were not
      significantly affected by host size. The observations that distributions vary
      between species and are not affected by host size do not support an earlier
      hypothesis which states that A. simplex L3 distributions are determined by an
      optimal pre-encapsulation migratory distance within host tissues. In contrast, it
      is suggested that A. simplex L3 distributions are governed by the conditions
      encountered within host tissues, and are possibly related to the availability of
      nutrients.

PMID- 9569093
TI  - The effect of azadirachtin on fresh isolates of Trypanosoma cruzi in different
      species of triatomines.
AB  - The effect of azadirachtin was investigated using three different fresh isolates
      of Trypanosoma cruzi and five different triatomine species which were infected as
      third-instar larvae. The two T. cruzi strains which originated from sylvatic
      Triatoma vitticeps showed a high prevalence after the molt to the fifth instar in
      Panstrongylus megistus and Rhodnius neglectus and a low prevalence in Triatoma
      infestans and Rhodnius robustus. The third T. cruzi strain originating from a
      patient in Piaui showed a high prevalence in P. megistus, R. neglectus and T.
      infestans and a low prevalence in Triatoma sordida. Feeding the infected fifth
      instars with azadirachtin-supplemented blood (1 microg/ml) resulted 20 days later
      in some parasite/vector combinations in an increase, in others a decrease or an
      unchanged number of T. cruzi in comparison to bugs fed with unsupplemented blood.

PMID- 9569094
TI  - A merozoite-specific 22-kDa rhoptry protein of the coccidium Eimeria nieschulzi
      (Sporozoa, Coccidia) is exocytosed in the parasitophorous vacuole upon host cell
      invasion.
AB  - A monoclonal antibody (Mab D12A4) was used to follow the genesis and fate of
      rhoptries from early first-generation merogony through second-generation
      merozoites of the rat coccidium Eimeria nieschulzi. The epitope recognized by Mab
      D12A4 belongs to a 22-kDa protein which can be localized first in developing
      meronts 25 h post-infection. Early rhoptries appear as distinct granules in the
      cytoplasm of developing meronts and elongate into mature organelles before
      merozoite release. The 22-kDa protein is found in the parasitophorous vacuole
      after host cell invasion. Western blotting and immunofluorescence showed that the
      22-kDa rhoptry protein is expressed in schizonts and merozoites but not in
      sporozoites.

PMID- 9569095
TI  - Differentiation between human and animal isolates of Cryptosporidium parvum using
      molecular and biological markers.
AB  - Isolates of Cryptosporidium parvum obtained from infected humans, calves and
      lambs were typed using arbitrary primed polymerase chain reaction (AP-PCR) and
      isoenzyme electrophoresis. All animal isolates tested (n = 17) showed similar
      profiles in AP-PCR and isoenzyme typing. In AP-PCR assays, 9 out of 15 human
      isolates showed a distinct "human" profile while the remaining 6 isolates showed
      the "animal" profile. In isoenzyme typing, 5 human isolates which had shown
      "human" profiles in AP-PCR demonstrated a unique isoenzyme banding pattern, while
      2 isolates which had shown "animal" profiles in AP-PCR gave the "animal" banding
      pattern. In a murine model of infection, all four animal isolates tested were
      highly infective but only one of four human isolates identified as "human" type
      in the AP-PCR and isoenzyme typing systems was infective. The good correlation
      between the data from the different typing systems supports the hypothesis that
      there are genetically distinct human and animal populations of C. parvum.

PMID- 9569096
TI  - In vitro cultivation of an African strain of Babesia bigemina, its
      characterisation and infectivity in cattle.
AB  - An African (Kenyan) strain of Babesia bigemina, Muguga (B(2-1)), was inoculated
      into a calf from a stabilate and blood from the calf was used to establish the
      parasite in vitro. The strain has been cultured continuously for 20 months,
      initially in bovine erythrocytes with 60% adult bovine serum, later, with 50%.
      Cultures were incubated at 37 degrees C in RPMI 1640 medium with a gas mixture of
      1% O2, 5% CO2, 94% N2. Adaptation in vitro was demonstrated when serum from a
      calf which had recovered from infection with B(2-1) bound to proteins of Mr 46
      kDa, 49 kDa, 52 kDa, 61 kDa and 72 kDa on Western blots of B(2-1) antigens from
      cattle blood but did not recognise the 49 kDa or 52 kDa antigens from in-vitro
      derived parasites. These proteins were considered specific for B(2-1), as they
      were not recognised by the same serum on profiles of a Mexican isolate of B.
      bigemina or an African isolate of B. bovis (Kwanyange). After 9 months of in
      vitro culture, a stabilate of the cultured parasite was injected into two
      splenectomised calves and one intact calf. The calves experienced a drop in
      packed cell volume and low parasitaemias but recovered spontaneously. Two of
      these animals, one splenectomised and one intact, were challenged with virulent
      B(2-1) and experienced only mild babesiosis, in contrast to a previously
      uninfected calf also challenged with B(2-1), which had to be euthanised after 5
      days with severe babesiosis.

PMID- 9569097
TI  - Isolation of an Entamoeba histolytica intracellular alkaline phospholipase A2.
AB  - The major hemolytic activity of Entamoeba histolytica is located in a subcellular
      fraction called P30. Its maximal effect is observed at pH 8.0 and 1 mM Ca2+ and
      is due to a phospholipase A (PLA). In the present study a membrane-associated
      phospholipase A2 was purified from P30 to homogeneity. P30 was fractionated with
      ethyl ether and the insoluble fraction was extracted with 1 M KCl. The KCl
      soluble material was diluted ten times with 0.1 M TRIS-HCl (pH 9.5) and passed
      through a chromatofocusing column with a 9-4 pH gradient. Four peaks with PLA2
      activity were obtained. By affinity chromatography, peak II, the one with the
      highest specific activity, was resolved in three more PLA2 peaks. Peak II.2 had
      the highest PLA2 specific activity. When analyzed by sodium dodecyl sulfate
      polyacrylamide slab-gel electrophoresis under nonreducing conditions, peak II.2
      yielded a single band with an apparent molecular mass of 30 kDa. Under reducing
      conditions the protein dissociated into two 15-kDa monomers. The purified PLA
      II.2 displayed its activity at the same conditions under which the P30 hemolytic
      activity was maximal. The isoelectric point of PLA II.2 was 7.0. The purification
      procedure described above provides sufficient material for determination of the
      relative importance of the enzyme in the E. histolytica pathogenic mechanisms.

PMID- 9569098
TI  - Microhabitat distribution and coexistence of Microcotylidae (Monogenea) on the
      gills of the striped mullet Mugil cephalus: chance or competition?
AB  - The two monogenean species Metamicrocotyla cephalus and Microcotyle mugilis have
      specific microhabitats on the gills of Mugil cephalus on which they may or may
      not coexist. M. cephalus is found in sector 1 of the posterior hemibranch of arch
      I. M. mugilis is found on the filaments of sector 5 of the posterior hemibranch
      of arch I. The coexistence of these two monogenean species on the same fish does
      not induce a change in their respective distribution, except for a marked
      preference of M. cephalus for the left side and of M. mugilis for the right. This
      15-month-long study shows that when the two species of monogeneans coexist the
      infection prevalence and intensity are higher than in cases of monospecific
      infection. The specific character of the microhabitat, the apparent absence of
      interspecific competition, and the existence of positive species interactions are
      discussed.

PMID- 9569099
TI  - Glycerol with fetal calf serum--a better cryoprotectant for Blastocystis hominis.

PMID- 9569100
TI  - Effect of time on migration of Oesophagostomum spp. and Hyostrongylus rubidus out
      of agar-gel.
AB  - The agar-gel migration technique has previously been described, however, aspects
      regarding the effect of timing on worm migration needed further scrutiny. In the
      first experiment, pigs inoculated with Oesophagostomum dentatum were slaughtered
      simultaneously and their intestines stored at 21-23 degrees C until processed
      pairwise 2, 4, 6, 8, 12 and 18 h after slaughter. More than 95% of the worms
      migrated out of the agar if processed within 6 h. In the second experiment,
      intestines were treated immediately after slaughter and the migratory speed of
      adult worms or 4th-stage larvae of O. dentatum or O. quadrispinulatum, or adult
      Hyostrongylus rubidus were studied. For both Oesophagostomum species, more than
      90% of the worms were recovered within 1 h. H. rubidus was significantly slower;
      however, approximately 98% of the worms had migrated out of the agar-gel by 20 h.
      This information is essential in planning experiments where recovery of live
      worms is of value.

PMID- 9569101
TI  - Trypanosoma cruzi: IgG1 and IgG2b are the main immunoglobulins produced by
      vaccinated mice.
AB  - Mice vaccinated with CL-14, a non-infective and non-pathogenic clone isolated
      from Trypanosoma cruzi CL strain, become protected against lethal challenge by
      infective trypomastigotes. It has been shown that animals infected with T. cruzi
      show polyclonal activation of B lymphocytes with an early production of several
      non-specific immunoglobulins. Vaccinated mice, however, have an early production
      of antigen-specific IgG1 and IgG2b. Considering the lack of infectivity of CL-14,
      our data strongly suggest a role for IgG1 and IgG2b in protection to T. cruzi.

PMID- 9569102
TI  - Schistosoma haematobium, S. intercalatum, S. japonicum, S. mansoni, and S.
      rodhaini in mice: relationship between patterns of lung migration by
      schistosomula and perfusion recovery of adult worms.
AB  - The development of five schistosome species was compared in mice by the recovery
      of schistosomula from chopped lung tissue and of adult worms by portal perfusion.
      Three developmental patterns appeared. (1) Schistosoma japonicum was unique in
      showing an early establishment of schistosomula in and a rapid departure from the
      lungs together with the highest worm recovery; (2) S. haematobium contrasted by
      establishing later and persisting in the lungs for at least 2 weeks while
      yielding the lowest adult worm recovery; and (3) S. intercalatum, S. mansoni, and
      S. rodhaini had an intermediate pattern--they resided in the lungs for several
      days, then disappeared and produced intermediate numbers of adults. Lung
      petechiae, known to accompany the migration of S. japonicum, were never detected
      after infection with the other species. We speculate that the three migration
      patterns of schistosomes are related to the size of the relative spectra of
      naturally infected definitive hosts.

PMID- 9569103
TI  - Evolution of lithogenic urinary parameters with a low dose potassium citrate
      treatment.
AB  - The changes in some nocturnal urine urolithogenic parameters in response to the
      extradietary ingestion of 2.16 g potassium citrate (20 meq) after dinner have
      been determined. The study included 15 patients (hypocitraturic calcium oxalate
      stone formers). On the basis of the different pH changes three groups have been
      differentiated. Different kinetics of citrate metabolism can justify the
      existence of these three groups. In general, a beneficial effect on urolithogenic
      parameters was confirmed, and a pH control of patients under treatment was
      recommended.

PMID- 9569105
TI  - Management of haematuria due to secondary renal tumour with selective arterial
      embolization.

PMID- 9569104
TI  - Solitary sacral soft tissue metastasis from renal cell carcinoma.

PMID- 9569106
TI  - Spontaneous (renal) pelvic rupture. Two cases cured by conservative therapy.
AB  - Two cases of spontaneous pelvic rupture are presented. In Case 1 (female, 49
      years) and Case 2 (male, 63 years) the rupture was due to obstruction and
      tumorous compression of the ureter, respectively. Authors deal with the
      diagnostic difficulties and the possibility of a cure without open surgery.
      Conservative therapy (double-J ureteral catheter and pigtail catheter) was
      successful in both cases. The pertinent literature is briefly reviewed.

PMID- 9569107
TI  - Juxtadrenal schwannoma.
AB  - Schwannoma which originated from Schwann cells is a nerve sheath tumour.
      Schwannomas of the urogenital tract are very rare. We present a case of a
      juxtadrenal schwannoma in a 66 years old female patient. To date only three
      juxtadrenal schwannoma cases have been described in the literature.

PMID- 9569108
TI  - Detection of source of haematuria after extracorporeal shock wave lithotripsy
      (ESWL) by automated measurement of urinary red cell volume.
AB  - Midstream urine samples taken from 35 patients with secondary haematuria due to
      nephrolithiasis and 31 patients with haematuria after ESWL were compared using a
      red cell analyser (RCA) to differentiate the source of haematuria. Urine samples
      obtained from both groups were examined by RCA for urinary red cell mean
      corpuscular volume (UMCV) and urinary red cell volume distribution curves
      (RCVDC). To rule out the influence of blood MCV (BMCV), BMCVs were determined
      separately and the ratio of UMCV/BMCV (R) was calculated. Although our findings
      showed no difference between haematurias after ESWL and nephrolithiasis, we
      cannot exclude a direct effect of shock waves on renal tissue.

PMID- 9569109
TI  - A retroperitoneal abscess with cutaneous fistula developed after stercoral
      fistula operation: a case report.

PMID- 9569111
TI  - Experiences with clam ileocystoplasty.
AB  - Clam ileocystoplasty was performed in 18 patients with urge incontinence, total
      incontinence or enuresis with instable detrusor. Although the persistence of
      detrusor instability was observed in 33.33% of the patients, complete clinical
      cure was found in 72.23 and symptomatic improvement was 22.22%.

PMID- 9569110
TI  - Prospective randomized comparison of intravesical BCG therapy with standard dose
      versus low doses in superficial bladder cancer.
AB  - In this study, we evaluated low dose intravesical bacillus Calmette-Guerin (BCG)
      therapy following transurethral resection (TUR) in 80 patients with superficial
      bladder cancer. The patients were divided into two groups. Of the Connaught BCG
      strain 81 mg was given to 40 patients in Group 1 and 54 mg to the remainder of 40
      patients in Group 2. BCG was introduced once a week for 6 weeks. Tumour
      recurrence was seen in 6 patients in Group 1 and in 10 patients in Group 2.
      Recurrence rates per month were 0.71 and 1.49, respectively. There was no
      significant difference in complication rates. These data suggest that while the
      standard dose (81 mg) intravesical therapy of BCG is more effective than the low
      dose, there was no significant difference in side effects between the two groups.

PMID- 9569112
TI  - What is your diagnosis?

PMID- 9569113
TI  - The effects of ejaculation on serum prostate-specific antigen (PSA).
AB  - To determine the effects of ejaculation on serum PSA, we measured serum levels
      just before masturbation and 24 hours and 5 days later in a study group (n=25)
      aged between 23 and 25 years. In the study group, 16 cases showed a decrease
      (mean 22.37%, range 10-50%) in serum PSA levels 24 hours after ejaculation, while
      6 had higher levels (mean 38.33%, range 21-67%) and 3 had no changes. No relation
      was found between seminal plasma levels or total amounts expelled of this marker
      and the difference in serum levels due to ejaculation. In the control group free
      of ejaculation in the same period determinations of serum PSA levels revealed no
      significant changes between days 0, 1 and 5. As compared with the control group,
      the changes in the study group were found to be statistically insignificant.
      These results may indicate that ejaculation has an insignificant effect on serum
      PSA levels.

PMID- 9569114
TI  - A simple ultrasonographic test for preoperative haemodynamic evaluation of
      varicocele.
AB  - According to the haemodynamic classification of varicocele type I is caused by
      renospermatic reflux due to a proximal nutcracker phenomenon or to valvular
      insufficiency of the left internal spermatic vein. Type II is due to
      ileospermatic reflux and type III may be characterized by a combination of I and
      II refluxes. Although this classification proposed by Coolsaet is precious for
      decision making, it is seldom used in clinical practice being based on a complex
      angiographic evaluation which is invasive and exposes the patient (often a
      teenager or with infertility disturbances) to excessive radiations. The aim of
      the present study was to work up an original ultrasonographic test for
      preoperative haemodynamic evaluation of varicocele in order to indicate the most
      appropriate microsurgical treatment. Sixty-three patients underwent a
      preoperative clinico-echographic dynamic test which allowed to classify 76.9% of
      the cases as haemodynamic type I, 10.7% as type II and 12.3% as type III.
      Microsurgical shunts were performed in all cases and evaluation of recurrences
      was accurately carried out with ultrasonographic measurement of residual
      varicosities. In 6% of the cases varicosities were consistently reduced in size
      and in 94% absence of varicosities was demonstrated. Varicocele increased in size
      or was unchanged in none of the cases. In conclusion the test hereby described
      was shown to be simple and easily reproducible. It allowed a haemodynamic and
      objective classification of varicocele offering a unique opportunity for
      tailoring to the individual patient the most appropriate treatment. Furthermore,
      ultrasonographic postoperative follow-up is the most reliable and objective
      method to control the "true" incidence of post-varicocelectomy recurrences.

PMID- 9569115
TI  - Low inguinal approach for correction of recurrent varicocele.
AB  - The purpose of this study was to evaluate the efficacy of low inguinal (or
      subinguinal) approach in the treatment of recurrent or persistent varicocele
      after surgical treatment. Recurrent varicocele was diagnosed in 23 patients who
      previously underwent surgical treatment. The technique used consisted of low
      inguinal incision at the level of the external inguinal ring without opening the
      external oblique aponeurosis. External spermatic veins (cremasteric veins) were
      dissected and selectively ligated. Then the spermatic fascia was incised and the
      internal spermatic veins were identified and ligated individually. Postoperative
      radioisotope scan, scrotal examination and sperm analysis were used for treatment
      evaluation. Twenty-one (91.3%) had negative postoperative scan and no signs of
      varicocele on physical examination. A marked improvement of sperm analysis was
      noted in 19 patients (p<0.05), while two had only minor improvement. Two patients
      had positive postoperative scans without improvement of semen analysis. Neither
      atrophy nor azoospermia were detected on follow-up examination in any of these
      men, however, one patient developed hydrocele. This study indicates a good
      surgical outcome and improvement of semen quality without significant
      complications.

PMID- 9569116
TI  - Evaluation of the role of corpus cavernosum electromyography as a noninvasive
      diagnostic tool in male erectile dysfunction.
AB  - Corpus cavernosum electromyography (EMG) and its evolution: single potential
      analysis of cavernous electrical activity (SPACE) seem to be promising diagnostic
      methods in the evaluation of erectile dysfunction and smooth muscle integrity.
      Our study concentrates on the role of EMG in the evaluation of corpus cavernosum
      smooth muscles, using it as a noninvasive technique for demonstrating autonomic
      erectile dysfunction through their influence on recording SPACE and consequent
      proper selection of patients for different therapeutic modalities. A total of 80
      male patients were examined for the feasibility of transcutaneous registration of
      cavernous electrical activity with a 2-channel electrophysiological unit
      (Evamatic 2000, Dantec) with two surface electrodes bilaterally placed on the
      penile shaft. Ten patients had normal erectile function, but complained of other
      urological symptoms. They served as the controls for normal electrical activity.
      Fifty patients with organic impotence of nonvascular (neurogenic) or vascular
      (venogenic, arteriogenic) aetiologies were subjected to EMG in both the flaccid
      and the erect state. On the basis of the EMG patterns the patients were divided
      into the following groups: 34 patients having normal tracing in both the flaccid
      and the erect state, and 21 patients showing abnormal patterns of waves with
      evidence of autonomic neurogenic dysfunction and incomplete smooth muscle
      relaxation. Of the latter 4 had long-standing diabetes mellitus and 4 had spinal
      injuries.

PMID- 9569117
TI  - Treatment of premature ejaculation with sertralin.
AB  - To evaluate the efficacy of oral sertralin in the treatment of premature
      ejaculation, out of 22 patients with premature ejaculation 16 received oral
      sertralin, 50 mg a day for at least 2 weeks. Four patients were lost to follow
      up. Two patients interrupted treatment due to side effects of sertralin. Out of
      16 patients who completed at least a two-week period of treatment 14 (87.5%)
      responded clinically. Clinical response was achieved in the first week of
      treatment in 11 of 16 responders (68.75%). We conclude that low dose oral
      sertralin may be useful with a reasonable side effect rate in the treatment of
      patients suffering from premature ejaculation.

PMID- 9569118
TI  - Contribution of transcutaneous ultrasonography to the evaluation of urethral
      strictures.
AB  - The aim of our study was to investigate the accuracy and sensitivity of
      ultrasound in detecting urethral strictures. Between 1992 and 1994, 117 patients
      with stricture of the anterior urethra were evaluated by retrograde
      urethrography, ultrasonography and urethroscopy.

PMID- 9569119
TI  - Subcutaneous r-HuEPO therapy in CAPD patients: dose determination and clinical
      experience.
AB  - We present our results on the efficacy and safety of low dose r-HuEPO given
      subcutaneously in the treatment of anaemia in CAPD. We have studied 10 stable
      patients (5 males, 5 females) on CAPD. In our study subcutaneous r-HuEPO was
      administered twice a week for 6 months. Mean initial dose of r-HuEPO was 67.3+/
      21.7 U/kg/week, and maintenance dose was 35.8+/-12.1 U/kg/week. The target Hb
      concentration was 10-12 g/dl. All patients responded to r-HuEPO. During treatment
      significant increases of haemoglobin concentration (p<0.05), haematocrit
      (p<0.05), red cell count (p<0.05) and reticulocyte count (p<0.05) were observed.
      We found no significant changes in total white cell or platelet counts. Long-term
      r-HuEPO treatment did not influence significantly plasma levels of electrolytes
      (Na, K, Ca), urea and creatinine. We found no significant changes in
      ultrafiltration volumes. In the present study the mean systolic and diastolic
      blood pressures did not change. Liver function tests were normal at the beginning
      and at the end of the study. r-HuEPO treatment was associated with a decrease of
      ferritin (455+/-90 vs. 224+/-83 microg/l. Oral or intravenous iron substitution
      became necessary in 6 patients. Side effects in our study were minimal; one
      patient had myalgia after the first seven doses but this disappeared as treatment
      was continued. Two patients reported pain (mild) at the injection site. In the
      present study, the correction of anaemia was accompanied by a substantial
      improvement in the quality of life, mainly in capacity for work, household and
      social activities.

PMID- 9569120
TI  - Serum level of carboxyterminal propeptide of type I procollagen in haemodialysis
      patients.
AB  - Serum concentrations of carboxyterminal propeptide of type I procollagen (PICP)
      and carboxyterminal parathyroid hormone (C-PTH) were measured in 33 haemodialysis
      patients. Serum levels of PICP and C-PTH in the haemodialysis group were
      significantly higher than those in the controls. Although there was no
      correlation between serum C-PTH and creatinine, a positive correlation was found
      between PICP and creatinine. This indicates that the measurement of PICP in serum
      is useful for monitoring metabolic bone diseases in haemodialysis patients.

PMID- 9569121
TI  - What holds us together? Why do some of us fall apart? What can we do about it?
AB  - One of the intriguing questions about complex organisms is, What holds them
      together? One of the principal answers is the tough, fibrous material known as
      collagen. A related question is, How is collagen made? The biosynthesis of the
      protein has several unusual features. One is the extensive use of the principle
      of spontaneous self-assembly seen in the formation of crystals. The three
      polypeptide chains of the protein fold into a triple-helical conformation by a
      process that begins with the formation of a small nucleus of triple helix at the
      C-terminus of the molecule and then propagation of the nucleus in a zipper-like
      fashion. Also, the self-assembly of the collagen monomers into fibrils is an
      entropy driven, crystallization-like process. Why do some of them fall apart?
      Mutations that alter the expression or primary structure of collagen are the
      predominant causes of severe skeletal defects such as osteogenesis imperfecta and
      chondrodysplasias. Mutations that have milder effects on the synthesis or
      structure of the protein are found in a subset of patients with more common
      diseases such as osteoporosis and early onset osteoarthritis. What can we do
      about the defects in collagen? Recent results have emphasized the importance of
      earlier observations that bone marrow contains a small subset of cells that are
      progenitors of osteoblasts, chondroblasts and several other types of
      nonhematopoietic cells. After systemic infusion into irradiated mice, the infused
      cells slowly replace a small fraction of the cells in bone, cartilage, lung and
      several other tissues. Therefore, the results suggest that the cells, known as
      mesenchymal stem cells or marrow stromal cells, can be used for both cell and
      gene therapy of diseases in which bone, cartilage and other connective tissues
      fall apart.

PMID- 9569122
TI  - Toward understanding SOX9 function in chondrocyte differentiation.
AB  - The transcription factors that trigger the determinative switch to chondrocyte
      differentiation in mesenchymal cells are still unknown. In humans, mutations in
      the gene for SOX9, a transcription factor with a DNA-binding domain similar to
      that of the mammalian testis-determining factor SRY, cause campomelic dysplasia,
      a severe dwarfism syndrome which affects all cartilage-derived structures. During
      mouse embryonic development, the Sox9 gene becomes active in all prechondrocytic
      mesenchymal condensations, and at later stages its expression is maintained at
      high levels in fully differentiated chondrocytes. A chondrocyte-specific enhancer
      in the gene for collagen type II (Col2a1), a characteristic marker of
      chondrocytes, is a direct target for SOX9, and ectopic expression of SOX9 in
      transgenic mouse embryos is sufficient to activate the endogenous Col2a1 gene in
      some tissues. These data suggest that SOX9 could have a major role in
      chondrogenesis. Studies are in progress to identify other target genes for SOX9
      in chondrocytes and also other transcription factors that are believed to
      cooperate with SOX9 in the activation of chondrocyte-specific genes. Defining
      SOX9 function and the mechanisms that regulate SOX9 gene expression should
      contribute to a better understanding of chondrocyte differentiation.

PMID- 9569123
TI  - Aggrecan and link protein affect cell adhesion to culture plates and to type II
      collagen.
AB  - Cartilage is a hypocellular tissue in which a balance of matrix molecules,
      especially aggrecan and link protein, play a critical role in maintaining
      structural integrity. To study the role of aggrecan and link protein in mediating
      cell activities, we have stably expressed them in NIH/3T3 fibroblasts and
      observed the effect on cell-substratum interactions. Overexpression of either
      protein destabilized the cell-substratum interaction. However, when both were co
      expressed, the interaction between cell and substratum was less impaired. Similar
      results were obtained on type II collagen-coated plates. The addition of
      exogenous gene products into fibroblast cell lines and chondrocyte culture had
      the same effect as expression of the genes. The addition of exogenous hyaluronan
      to the growth medium or treatment of cells with hyaluronidase also decreased cell
      adhesion, indicating that hyaluronan also plays a role in the cell-substratum
      adhesion. The presence of aggrecan seems to increase the amount of link protein
      on the cell surface. Chondrocytes expressing high concentrations of aggrecan and
      link protein were maintained within a matrix network and were able to survive in
      suspended culture. Imbalances in aggrecan or link protein concentrations, or
      degradation of hyaluronan, disrupted the network and caused the chondrocytes to
      aggregate or adhere to the plates.

PMID- 9569124
TI  - Sequence, structure and chromosomal localization of Crtm gene encoding mouse
      cartilage matrix protein and its exclusion as a candidate for murine
      achondroplasia.
AB  - The mouse cartilage matrix protein gene (Crtm) was isolated from a cosmid library
      using a mouse Crtm cDNA fragment as probe. Crtm spans 12.2 kb from the start of
      translation to the polyadenylation signal sequence and comprises eight exons.
      Sequencing of the 1.9 kb 5' flanking region revealed a TATA-like box 72 bp
      upstream from the initiator Met codon as well as several cis-acting motifs known
      to bind eukaryotic transcription factors. Analysis of the exon-intron junctions
      demonstrated that the last intron does not follow the gt/ag rule but belongs to
      the minor class of pre-mRNA introns that contain "at" and "ac" at their 5'and 3'
      ends, respectively. Single-strand conformation polymorphism analysis was used to
      map Crtm to the distal part of chromosome 4 between the microsatellite markers
      D4Mit16 and D4Mit339. Achodroplasia (cn), a recessive skeletal disorder in mice,
      has already been mapped to this region. Immunostaining for CMP and sequence of
      Crtm in cn/cn mice failed to reveal any disease-specific mutations, suggesting
      that mutations in Crtm do not cause achondroplasia.

PMID- 9569125
TI  - Participation of intracellular cysteine proteinases, in particular cathepsin B,
      in degradation of collagen in periosteal tissue explants.
AB  - The involvement of cysteine proteinases in the degradation of soft connective
      tissue collagen was studied in cultured periosteal explants. Using cysteine
      proteinase inhibitors that were active intracellularly or extracellularly (Ep453
      and Ep475, respectively), it was shown that over-all collagen degradation, as
      measured by the release of hydroxyproline, decreased significantly on inhibition
      of the intracellular pool of cysteine proteinases by Ep453. This inhibitor also
      induced an accumulation of intracellular fibrillar collagen in fibroblasts,
      indicating a decreased degradation of phagocytosed collagen. The extracellular
      inhibitor, Ep475, had minor or no effects. Histochemical analysis using a
      substrate for the cysteine proteinases cathepsins B and L revealed a high level
      of enzyme activity, which was completely blocked in explants preincubated with a
      selective intracellular inhibitor of cathepsin B, Ca074-Me. Moreover, the
      cathepsin B inhibitor strongly affected collagen degradation, decreasing the
      release of hydroxyproline and increasing the accumulation of phagocytosed
      collagen. These effects were comparable or slightly stronger than those found
      with the general intracellular inhibitor (Ep453). Taken together, these data
      strongly suggest that intracellular cysteine proteinases, in particular cathepsin
      B, play an important role in the digestion of soft connective tissue collagen.

PMID- 9569126
TI  - End-stage renal disease among Asians.

PMID- 9569127
TI  - Hyperhomocysteinemia as a cause of vascular occlusion in end-stage-renal disease.

PMID- 9569128
TI  - Platelet-neutrophil interactions during hemodialysis: a proposed biocompatibility
      approach.
AB  - Platelet interaction with neutrophils may occur to a significant degree during
      hemodialysis (HD). We have recently shown that the enhanced neutrophil reactive
      oxygen species (ROS) production during the early phase of HD with cuprophan (CUP)
      is sustained by neutrophils which have bound platelets through P-selectin
      (CD62P). The evaluation of platelet-neutrophil interactions during dialysis
      offers the novel aspect of cell-cell interactions as a new parameter for studying
      the biocompatibility of dialyzer membranes. By the use of flow cytometry
      techniques, the present study was set up to analyze intradialytic platelet
      neutrophil coaggregate formation and neutrophil ROS (hydrogen peroxide)
      production from 6 HD patients each dialysed with CUP, cellulose diacetate (CDA),
      polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN) in a cross-over
      clinical trial. Platelet-neutrophil coaggregate formation (percentage of
      neutrophil cells positive for CD62P) and ROS production by neutrophils (total
      population; CD62P+ cells; CD62P- cells) were determined before HD and after 10',
      20'and 40'. CD62P+ neutrophils significantly increased during HD with CUP (10',
      20', 40'), PMMA (20') and CDA (20), while no change was observed with PAN. The
      difference between CUP and the other membranes was significant at 10', 20' and
      40'; at 20', PMMA vs PAN p<0.005. ROS production by total neutrophil population
      significantly increased with CUP (10', 20), PMMA (20) and CDA (20'). The increase
      with CUP was higher at 10' when compared to CDA (p<0.020) or PAN (p<0.005), and
      at 20' versus the other three membranes; at 20' PMMA vs PAN p<0.005. Only
      neutrophils gated in neutrophil-platelet coaggregate areas (CD26P+ neutrophils)
      produced hydrogen peroxide. ROS production by CD62P+ neutrophils significantly
      increased with CUP (10', 20), PMMA (20') and CDA (20'). The increase with CUP was
      significantly (p<0.0002) higher than the other three membranes at 10' and 20'; at
      20', PMMA vs PAN p<0.02. With each membrane, ROS production by CD62P- neutrophils
      showed no significant change at any time point during HD. The results of the
      present study indicate that interactions between platelets and neutrophils can
      mediate some pathophysiological abnormalities associated with hemodialysis
      treatment. Our data show that cellulose diacetate, a modified cellulosic
      membrane, exhibits a biocompatibility profile in terms of platelet-neutrophil
      interactions improved as compared to the parent cellulose membrane and comparable
      to that of some synthetic membranes. Our data also show that there is
      considerable variability in the biocompatibility of synthetic membranes. Though
      cellulosic membranes are generally considered as being less biocompatible than
      synthetic membranes, our results indicate that classification of membranes by
      biocompatibility is more complex than a simple division into cellulosic and
      synthetic membranes, especially with the advent of modified cellulosic membranes.

PMID- 9569129
TI  - Elevated levels of tumor necrosis factor alpha in postdialysis fatigue.
AB  - Postdialysis fatigue (PDF) has been ascribed to excessive ultrafiltration and
      decline in osmolality during hemodialysis. We evaluated the potential role for
      the sommogenic cytokines, interleukin-1 beta (IL-1beta) and tumor necrosis factor
      alpha (TNFalpha), in the genesis of PDF Patients dialyzing with cuprophane
      membrane were assigned to PDF (N=25) and non-PDF (N=25) groups based on a fatigue
      index questionnaire. Pre- and postdialysis samples were obtained from 3
      consecutive treatments and later assayed for serum levels of IL-1beta and
      TNFalpha by ELISA. Our results show significant intradialytic elevation of
      TNFalpha in both non-PDF groups (non-PDF: pre- 3.36+/-0.80 pg/ml to post 3.75+/
      0.88 pg/ml, p<0.04; PDF: pre- 5.95+/-0.80 pg/ml to post- 8.66-/+1.35 pg/ml,
      p<0.02). The degree of intradialytic augmentation was significantly greater for
      TNFalpha in the PDF group (46+/-18% vs 11+/-5%; p<0.03). There were no
      significant intradialytic changes in serum levels of IL-1beta in either the PDF
      or non-PDF groups. There also were no significant differences in dialysis-related
      body weights, systolic blood pressures, or osmolalities. These findings suggest
      that TNFalpha may be involved in the pathogenesis of PDF.

PMID- 9569131
TI  - CAPD catheter rupture without deterioration.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is associated with various
      problems, including damage to the CAPD catheter. We encountered catheter rupture
      around the titanium adaptor in a patient who had been on CAPD for 7 years. The
      area near the adaptor generally suffers damage secondary to deterioration of the
      silicon composing the catheter. However, stereoscopic and electron microscopic
      observation of the surface of the catheter revealed no deterioration. Instead,
      there were fine scratches around the site of rupture and the broken surface was
      rough. Since the patient did not protect the catheter with gauze near the
      titanium adaptor, it was probably damaged by the adaptor and then ruptured by
      some external force.

PMID- 9569130
TI  - DEHP-induced alterations in the lining tissue of the rat air pouch.
AB  - The direct effects of D(2-ethylhexyl)phthalate (DEHP), on subcutaneous tissue
      were studied in the rat, using the air pouch technique. Two ml of DEHP either
      undiluted or diluted in olive oil (10 microm/ml), were introduced into a
      previously created air pouch in the rats. The air pouch was removed and specimens
      of the lining tissue examined by optical and electron microscopy. The persistence
      of DEHP for 7 days is sufficient to cause alterations in the tissue. The major
      histological changes were the destruction of the tissue organization with
      cytoplasmic and nuclear alterations resulting in apoptotic bodies. The
      histochemical data showed an increase of sulphated glycosaminoglycans, showing
      proof of alterations in fibroblast functions. The authors suggest that the
      hyperplastic-type alteration induced by DEHP may be connected with the sclerosis
      of the peritoneal membrane described in uremic patients in CAPD.

PMID- 9569132
TI  - Mass transfer efficiency of a commercial hollow fibre oxygenator during six-hour
      in vitro perfusion with steady and with pulsatile blood flow.
AB  - Detailed data about the behaviour of commercial membrane oxygenators with
      pulsatile blood flow are rarely available. This work deals with an experimental
      evaluation of the effects induced on gas transfer efficiency by pulsatile
      perfusion of a hollow fibre oxygenator (Monolyth Sorin Biomedica). The oxygenator
      was subjected to two in vitro trials both carried out with identical experimental
      protocols except for the flow type, steady and pulsatile. A roller pump with
      pulsatile module (Stockert Instrument) was used to generate both flow types.
      Three different mean blood flow rates (3.2, 4.0 and 4.8 L/min) were tested. The
      experiments lasting six hours were carried out using bovine blood with inlet
      conditions according to AAMI standard requirements. Blood samples were withdrawn
      every hour and the calculated gas transfer obtained in the two sessions were
      compared. The device proved to be well-designed for steady flow and to be liable
      to similar gas transfer performance when used in pulsatile conditions.
      Furthermore, the use of pulsatile flow rather than steady flow provided more
      consistent conditions and resulted in a higher eventual oxygen transfer
      efficiency (final mean difference = 6.2%, p < 0.05), proving to be able to avoid
      any performance decays.

PMID- 9569133
TI  - Shear stress related hemolysis and its modelling by mechanical degradation of
      polymer solutions.
AB  - Human or animal blood is normally used as a test fluid for in vitro evaluation of
      hemolysis by artificial organs. However, blood has some disadvantages (no
      transparence for visualization of the flow field, large biological variability
      and problems with cleaning the devices). For that reason, it would be of
      advantage to have a reproducibile transparent technical fluid with blood like
      flow characteristics and that exhibits similar shear depending destruction. We
      have shown that solutions of long-chaining polymer molecules are destroyed by
      heart valve prostheses in a similar manner as blood corpuscules. In the presented
      study, a direct comparison between erythrocyte destruction of bovine blood and
      degradation of Polyacrylamid molecules in a 300 ppm solution is given. A uniform
      shear field was applied to the fluid using a plate-plate geometry shear device.
      This device allows a variation of shear stress and shear time in the range of 15
      500 N/m2 and 64-516 ms, respectively A correlation between the index of hemolysis
      (ratio of free plasma hemoglobin to total hemoglobin) and the percentage
      viscosity decrease (derived from low shear viscosity at a shear rate of 0.01/s)
      was found. Thus, PAA solutions are suitable model fluids for in vitro estimation
      of the damaging effects of artificial devices.

PMID- 9569134
TI  - Mechanical effects of heart pulse propagation on a vessel-graft suture line
      stress.
AB  - The effects of vessel joint where the both sides have different wall properties
      on the heart pulse propagation are investigated. Such a local disturbance can
      influence post-transplantation pathology and evolution of the organ
      inconsistency. Using a mathematical model, developed in a previous article, we
      perform analytical analysis and present some qualitative and quantitative
      estimations. The effects of jointed vessels with different thicknesses and radii
      on the local concentration of the pressure, radial wall displacement, bending
      moment and shear force are analyzed in detail. In particular, it is obtained that
      the bending and shear stresses at a joint sharply and strongly increase in
      comparison with the uniform vessel ones.

PMID- 9569139
TI  - Women in veterinary medicine: overcoming adversity, achieving acceptance.

PMID- 9569135
TI  - European research and commercialisation activities in the field of tissue
      engineering and liver support in world wide competition.
AB  - Tissue engineering is seen as an interesting field of technology which could
      improve medical therapy and could also be considered as a commercial opportunity
      for the European biotechnological industry. Research in the state of the art of
      science using the MedLine and the Science Citation Index databases, in the patent
      situation and of the industry dealing with tissue engineering was done. A special
      method, based on the Science Citation Index Journal Citation Report 1993, for
      evaluating scientific work was defined. The main countries working in the field
      of tissue engineering were evaluated in regard to their scientific performance
      and their patents. The R&D of German industry was investigated as an exemplary
      European country. Out of all activities, different tissues were rated with
      respect to the attention received from research and industry and with regard to
      the frequency in which patents were applied for. USA, Germany and Japan rank
      first in most tissues, especially liver. After comparing German patents with the
      German scientific and industrial work, it seems that the potential in German
      patents and research is underestimated by German industry and inefficiently
      exploited.

PMID- 9569142
TI  - Mange, overpopulation in dogs on the rise in postwar Tarawa.

PMID- 9569143
TI  - Importance of ethics.

PMID- 9569144
TI  - More on dangerous dog breeds.

PMID- 9569145
TI  - More on dangerous dog breeds.

PMID- 9569146
TI  - More on dangerous dog breeds.

PMID- 9569147
TI  - Suspect relationship between fertilizers, tobacco stalks, and cadmium antagonism
      as a cause of tetany and induced mineral deficiencies in cattle.

PMID- 9569148
TI  - What is your diagnosis? Aggressive lytic lesions of the medullary and cortical
      bone of the distal diaphyses of the radius and ulna.

PMID- 9569149
TI  - Difficult dermatologic diagnosis. Pythiosis.

PMID- 9569150
TI  - Enrollment at veterinary medical colleges, 1996-1997 and 1997-1998.

PMID- 9569151
TI  - Large-scale human exposures to rabid or presumed rabid animals in the United
      States: 22 cases (1990-1996).
AB  - OBJECTIVE: To identify common elements of large-scale human exposures to rabid or
      presumed rabid animals in the United States from 1990 to 1996. DESIGN:
      Retrospective study. PROCEDURE: Health departments in 50 states and the District
      of Columbia were contacted regarding episodes of large-scale human exposures to
      rabid animals occurring between 1990 and 1996. A large-scale exposure was defined
      as administration of postexposure prophylaxis (PEP) to 25 or more people after an
      exposure to a rabid or presumed rabid animal or littermates. Incident-specific
      information was obtained through questionnaires sent to states reporting
      episodes. Data are reported as medians. RESULTS: Fifteen of 51 (29.4%) health
      departments reported 22 episodes; 72.7% involved companion animals or livestock.
      Twenty-six animals were involved in these 22 episodes, including 10 (38.5%) dogs,
      4 (15.4%) livestock, 4 (15.4%) raccoons, 3 (11.5%) cats, 3 (11.5%) bats, and 2
      (7.7%) ferrets. Schools (36.4%) and public places (22.7%) were the most common
      settings for exposures. Reportedly, 1,908 people received PEP. The cost for 10
      episodes was $61,547/episode (range, $14,199 to $1,500,000). An episode-specific
      written algorithm for recommending PEP had been developed for use in only 4
      (18.2%) episodes. CLINICAL IMPLICATIONS: Large-scale exposures most commonly
      involved a single companion animal. Exposures attributable to improper handling
      of wildlife and unrestricted access of animals in schools and public areas can be
      potentially remedied by targeted education. Use of an episode-specific algorithm
      to determine need for PEP may also reduce the number of unnecessary treatments.

PMID- 9569153
TI  - Role of veterinary therapeutics in bacterial resistance development: animal and
      public health perspectives.

PMID- 9569152
TI  - Injuries and illnesses in working dogs used during the disaster response after
      the bombing in Oklahoma City.
AB  - OBJECTIVES: To determine characteristics of working dogs used during the disaster
      response after the bombing in Oklahoma City and risk factors for injuries and
      illnesses of those dogs, and to document recommendations for future disaster
      responses. DESIGN: Survey. STUDY POPULATION: Information for 74 working dogs used
      at the bombing site. PROCEDURES: Dog handlers were identified and asked to
      complete a questionnaire. Questions were asked about the training and use of each
      dog, use of paw protection, injuries and illnesses incurred, possible effects
      after completion of duty at Oklahoma City, and handler's experience. RESULTS:
      Data were obtained for all 74 dogs used at the site. Handlers of 69 of 74 (93%)
      dogs responded. The dogs had been extensively trained and were used 491 dog-days
      at the site, with 46 dogs used in search, 14 in patrol, 12 in explosive-detection
      duty, and 2 in search/patrol. Fifteen (22%) dogs became ill. Nineteen (28%) dogs
      incurred 20 injuries. Footpad injuries constituted 18 of the injuries. Only 16 of
      69 (23%) dogs were provided with paw protection. Dogs were more likely to be
      injured when they were used in a search capacity, were used during the first 2
      days after the bombing, were German Shepherd Dogs, or were older. CLINICAL
      IMPLICATIONS: Although working in a high-risk environment, injuries to dogs were
      few, and most were minor. Specific recommendations could facilitate use of dogs
      in disaster situations and improve safety for those dogs.

PMID- 9569155
TI  - Appreciating avian intelligence: the importance of a proper domestic environment.

PMID- 9569154
TI  - Pet birds: historical and modern perspectives on the keeper and the kept.

PMID- 9569156
TI  - Considerations in selecting an appropriate pet bird.

PMID- 9569157
TI  - Twenty years of progress in pet bird nutrition.

PMID- 9569158
TI  - Twenty years of progress in pet bird research.

PMID- 9569159
TI  - Twenty years of progress in avian anesthesia and surgery.

PMID- 9569160
TI  - Emerging trends in pet bird diets.

PMID- 9569161
TI  - Perspectives on pet bird welfare from the pet industry.

PMID- 9569162
TI  - Captive management of birds for a lifetime.

PMID- 9569163
TI  - Adding value to nature through macaw-oriented ecotourism.

PMID- 9569164
TI  - Description and development of compulsive tail chasing in terriers and response
      to clomipramine treatment.
AB  - OBJECTIVE: To identify factors associated with onset and continued elicitation of
      tail chasing in Bull Terriers and other terriers and to determine response to
      treatment with clomipramine hydrochloride, a serotonin-reuptake inhibitor.
      DESIGN: Prospective study. ANIMALS: 18 tail-chasing terriers (15 Bull Terriers, 1
      Miniature Bull Terrier, 1 American Staffordshire Terrier, 1 Jack Russell
      Terrier). PROCEDURE: 5 dogs were evaluated for tail chasing by a veterinarian at
      the behavior clinic of the veterinary teaching hospital and 13 dogs were
      evaluated by the owner's local veterinarian, who confirmed the diagnosis and
      treated the dog. It was recommended that all dogs in the study be given
      clomipramine orally at a dosage of 1 to 2 mg/kg (0.5 to 0.9 mg/lb) of body
      weight, every 12 hours. RESULTS: Of the 18 dogs, 15 were treated with
      clomipramine within the recommended dosage range, and 3 dogs required treatment
      at a slightly higher dosage range to control tail chasing. After 1 to 12 weeks of
      treatment, 9 of 12 (75%) dogs were reported to have a 75% or greater improvement
      (reduction) in tail chasing. CLINICAL IMPLICATIONS: Findings of this study may
      aid in recognition and treatment of compulsive tail chasing. In conjunction with
      appropriate management changes, clomipramine administration appears to be an
      effective treatment for this otherwise refractory condition.

PMID- 9569165
TI  - Evaluation of microcytosis in 18 Shibas.
AB  - OBJECTIVE: To determine whether microcytosis is a typical finding in Shibas.
      DESIGN: Prospective study. ANIMALS: 18 Shibas. PROCEDURE: Blood and serum samples
      were obtained for automated hematologic analyses (18 dogs) and for determination
      of ferritin concentration, using ELISA (14 dogs). Blood samples from 30
      clinically normal dogs of various other breeds was analyzed to establish a
      reference range for ferritin concentration. RESULTS: Erythrocyte mean corpuscular
      volume in Shibas ranged from 55.6 to 69.1 fl (mean+/-SD, 61.2+/-4.3 fl; median,
      60.6 fl; reference range, 63 to 73 fl). Microcytosis was identified in 12 of 18
      dogs. Males and females were affected equally. Mean corpuscular hemoglobin
      concentration was slightly low (range, 32.0 to 33.9%; reference range, 34 to 38%)
      in 6 dogs, 4 of which had microcytic RBC. Serum ferritin concentrations ranged
      from 61.2 to 277.0 ng/ml (mean+/-SD, 110.6+/-51.4 ng/ml; median, 106 ng/ml).
      Reference range for serum ferritin concentration was 50.7 to 440.0 ng/ml (mean+/
      SD, 121.2+/-67.1 ng/ml; median, 111.5 ng/ml). Thrombocytopenia (range, 110,000 to
      196,000 platelets; reference range, 200,000 to 450,000 platelets) was found in 7
      dogs, 6 of which also had microcytic RBC. CLINICAL IMPLICATIONS: Microcytosis can
      be a typical finding in Shibas. Common origin of Shibas and Akitas, a breed
      predisposed to microcytosis, suggests a hereditary basis for this finding.

PMID- 9569166
TI  - Heinz body formation in cats fed baby food containing onion powder.
AB  - OBJECTIVE: To determine whether cats fed baby food with onion powder develop
      Heinz bodies and anemia and to establish a dose-response relation between dietary
      onion powder content and Heinz body formation. DESIGN: Prospective study.
      ANIMALS: 42 healthy, adult, specific-pathogen-free cats. PROCEDURE: Commercial
      baby food with and without onion powder was fed to 2 groups of 6 cats for 5
      weeks. Heinz body percentage, PCV, reticulocyte percentage, turbidity index, and
      methemoglobin and reduced glutathione concentrations were determined twice weekly
      and then weekly for 4 weeks following removal of the diet. For the dose-response
      study, 5 groups of 6 cats were fed a canned diet for 2 months that contained 0,
      0.3, 0.75, 1.5, or 2.5% onion powder. Heinz body percentage, PCV, and
      reticulocyte percentage were determined twice weekly. RESULTS: Compared with cats
      fed baby food without onion powder, cats ingesting baby food with onion powder
      had significantly higher Heinz body percentages that peaked at 33 to 53%.
      Methemoglobin concentration also significantly increased but did not exceed 1.2%.
      Glutathione concentration, PCV, and food intake did not differ between the 2
      groups. Rate and degree of Heinz body formation differed significantly between
      various onion powder concentrations fed. Compared with 0% onion powder, the diet
      with 2.5% onion powder caused a significant decrease in PCV and an increased
      punctate reticulocyte percentage. CLINICAL IMPLICATIONS: Baby food or other foods
      containing similar amounts of onion powder should be avoided for use in cats
      because of Heinz body formation and the potential for development of anemia,
      particularly with high food intake. Cats with diseases associated with oxidative
      stress may develop additive hemoglobin damage when fed baby food containing onion
      powder.

PMID- 9569167
TI  - Type-II external fixation, using new clamps and positive-profile threaded pins,
      for treatment of fractures of the radius and tibia in dogs.
AB  - A new external fixation system for repair of fractures of the radius and tibia
      was developed that uses positive-profile threaded pins. This system allows for
      addition of a fixation clamp between 2 installed clamps, predrilling of pin holes
      through a drill sleeve, use of positive-profile threaded pins in all locations,
      and easier application of full pins. Type-II external fixators were applied,
      using this system, to fractures in 10 client-owned dogs, and outcome was
      evaluated. All fractures healed without complications. Duration of surgery, mean
      time until radiographic evidence of a bridging callus, and mean time until
      removal of the external fixator were shorter, and frequency of pin loosening were
      less than with other techniques. Pin loosening was uncommon. This system provides
      an important improvement in external skeletal fixation.

PMID- 9569168
TI  - Adult-onset motor neuron disease in three cats.
AB  - Motor neuron diseases of domestic animals have rarely been described. Three cats
      with adult-onset, chronic, progressive generalized muscle weakness characterized
      initially by trembling on exertion and later by extreme difficulty in walking,
      cervical ventroflexion, dysphagia, and marked muscle atrophy were elevated.
      Spinal reflexes were evident early but were nondetectable as the disease
      progressed. Electromyography revealed fibrillation potentials, with nerve
      conduction velocities within the reference range. Histologic examination of
      muscle specimens revealed denervation. Marked neuron loss and gliosis were
      detected in the ventral horns of the spinal cord, with atrophy of ventral nerve
      rootlets. Less dramatic neuron loss was seen in brain stem motor nuclei. Electron
      microscopic examination of the ventral horns disclosed hypertrophied astrocytes,
      with densely arrayed intermediate filaments, swollen axons with large filamentous
      accumulations, and many macrophages with lipofuscin-like inclusions. Clinical and
      pathologic findings were consistent with a progressive neurodegenerative disease
      affecting spinal and some bulbar motor nuclei.

PMID- 9569169
TI  - Analysis of prognostic indicators for dogs with pericardial effusion: 46 cases
      (1985-1996).
AB  - OBJECTIVE: To determine factors associated with disease-free interval and
      survival time for dogs with pericardial effusion. DESIGN: Retrospective study.
      ANIMALS: 46 dogs. PROCEDURE: Signalment, history, results of physical
      examination, electrocardiography, echocardiography, and thoracic radiography;
      disease-free interval; and survival time were obtained from medical records or
      telephone conversations with owners and referring veterinarians. RESULTS: Dogs
      that had ascites at the time of the initial physical examination were
      significantly less likely, and dogs that had evidence of pulmonary metastases on
      thoracic radiographs or that had echocardiographic evidence of a right atrial
      mass were significantly more likely, to have died of pericardial effusion or the
      underlying cause of effusion than were dogs that did not. Median survival time
      was 15.3 months for dogs with idiopathic pericardial effusion, 16 days for dogs
      with hemangiosarcoma, and 13.6 months for dogs with mesothelioma. Dogs that had a
      nonspecific extracardiac mass and underwent pericardiectomy were significantly
      less likely to have had recurrence of signs than were dogs that did not. However,
      dogs with mesothelioma or hemangiosarcoma that underwent pericardiectomy did not
      have a significantly different risk of recurrence of signs or survival time,
      compared with dogs that did not. CLINICAL IMPLICATIONS: Results suggest that
      pericardiectomy will not affect risk of recurrence or survival time in dogs with
      pericardial effusion secondary to hemangiosarcoma or mesothelioma. However,
      pericardiectomy is still needed to differentiate dogs with neoplastic pericardial
      effusion from dogs with idiopathic pericardial effusion.

PMID- 9569170
TI  - What is the economic case for treating obesity?
AB  - From both societal and payer perspectives, the economic effect of obesity in the
      United States is substantial, estimated at approximately 6% of our national
      health expenditure and cost of care in a major health maintenance organization.
      The number of physician visits related to obesity has increased 88% in a 6-year
      period. The morbidity cost (lost productivity) and functional capability of the
      patient with obesity is increasing rapidly (50% increase in lost productivity,
      36% increase in restricted activity, and 28% increase in number of bed-days).
      Cost savings of treating obesity are comparable to those of treating other
      chronic diseases such as coronary heart disease and diabetes. Most studies
      indicate that most of the direct health care costs of obesity are from type 2
      diabetes, coronary heart disease and hypertension. To date, however, there have
      been no published reports of the cost effectiveness of the medical management of
      obesity treatment. In conclusion, the cost of obesity is comparable to that of
      other chronic diseases, yet it receives disproportionately less attention. Cost
      effectiveness studies need to be initiated promptly.

PMID- 9569171
TI  - The insulin resistance-dyslipidemic syndrome of visceral obesity: effect on
      patients' risk.
AB  - Coronary heart disease (CHD) and type 2 diabetes mellitus represent two highly
      prevalent conditions in affluent societies. Although a dyslipidemic state is
      frequently found in type 2 patients with obesity, studies have shown that the
      high triglyceride, low high-density lipoprotein (HDL) cholesterol dyslipidemia is
      also found in nondiabetic patients with insulin resistance. Studies that have
      used imaging techniques to assess the regional distribution of body fat have
      shown that an excess of visceral adipose tissue, that is, a high accumulation of
      fat in the abdominal cavity, was associated with a cluster of metabolic
      disturbances such as insulin resistance, hyperinsulinemia, glucose intolerance,
      hypertriglyceridemia, elevated apolipoprotein B (apoB) concentrations, small,
      dense low-density lipoprotein (LDL) particles, as well as low HDL cholesterol
      levels. Prospective studies such as the Quebec Cardiovascular Study have shown
      that this cluster of metabolic abnormalities commonly found in patients with
      excess visceral adipose tissue substantially increases the risk of CHD. The high
      prevalence of visceral obesity in sedentary adult men and postmenopausal women is
      such that it may represent the most prevalent cause of atherogenic dyslipidemic
      states associated with CHD in our population.

PMID- 9569173
TI  - The case for medical management of obesity: a call for increased physician
      involvement.
AB  - The United States is in the midst of an escalating epidemic of obesity. Over one
      third of the adult population in the United States is currently obese and the
      prevalence of obesity is growing rapidly. By any criteria, obesity represents a
      chronic disease which is associated with a wide range of comorbidities, including
      coronary heart disease (CHD), Type 2 diabetes, hypertension and dyslipidemias.
      The comorbidities of obesity are common, occurring in over 70% of individuals
      with a BMI of > or = 27. In addition to obesity itself, excessive accumulation of
      visceral abdominal fat and significant adult weight gain also represent health
      risks. Physicians have an important role to play in the treatment of obesity.
      Unfortunately, the medical community has not been involved actively enough to
      help stem the major epidemic of obesity occurring in the United States. This
      article puts forth a proposed model for the treatment of obesity in clinical
      practice, including obtaining the "vital signs" of obesity, recommending
      lifestyle measures, and instituting pharmacologic therapy when appropriate. By
      utilizing a chronic disease treatment model, physicians can join other health
      care professionals to effectively treat the chronic disease of obesity.
      Relatively modest weight loss, on the order of 5-10% of initial body weight can
      result in significant health improvements for many patients and represent an
      achievable goal for most obese patients.

PMID- 9569172
TI  - What is the role of cognitive-behavior therapy in patient management?
AB  - This review summarizes the role of cognitive-behavior therapy (CBT) in obesity
      treatment. Although not a specific intervention per se, CBT is the systematic
      application of principles of social cognitive theory to modify behaviors that are
      thought to contribute to or maintain obesity. Most forms of CBT include the use
      of five strategies: self-monitoring and goal setting; stimulus control for the
      modification of eating style, activity, and related habits; cognitive
      restructuring techniques that focus on challenging and modifying unrealistic or
      maladaptive thoughts or expectations; stress management; and social support. The
      use of these strategies in comprehensive obesity programs has been helpful in
      improving short-term weight losses, but long-term success remains elusive, even
      though these strategies are predictors of long-term weight loss maintenance.
      Given that obesity is a chronic condition, not unlike hypertension or diabetes,
      CBT interventions will need to focus on broader treatment outcomes, such as
      improved metabolic profiles, quality of life, psychological functioning, and
      physical fitness. In addition, new methods for delivering CBT interventions
      should be explored, including home-based programs and combination with adjunctive
      pharmacotherapy delivered in primary care centers.

PMID- 9569174
TI  - Dealing with obesity as a chronic disease.
AB  - There are major efforts underway to educate the primary care physician about the
      health risks of obesity. Obesity is a chronic disease that requires chronic
      management. We must establish models that allow primary care physicians to
      participate in the chronic management of obesity, while recognizing that the
      interest and ability of primary care physicians to participate in obesity
      management will vary. Three general models of obesity management are proposed for
      the primary care physician, ranging from minimal evaluation to complete
      evaluation and treatment. In order for the models to be implemented, we must
      consider establishing a category of obesity specialists who can develop
      comprehensive treatment programs to which patients with obesity can be referred,
      and who can provide leadership and guidance for primary care physicians who are
      involved in obesity management. The North American Association for the Study of
      Obesity (NAASO) could help establish obesity specialists and provide a structure
      to allow them to provide leadership for obesity treatment.

PMID- 9569175
TI  - The future of obesity management and health: it's time for a new approach--a
      roundtable discussion: conducted in conjunction with the annual meeting of the
      North American Association for the Study of Obesity, Cancun, Mexico, November 11,
      1997.

PMID- 9569176
TI  - Eicosanoids and iso-eicosanoids: constitutive, inducible and transcellular
      biosynthesis in vascular disease.

PMID- 9569177
TI  - Geographic distribution of the 20210 G to A prothrombin variant.
AB  - A variant in prothrombin (clotting factor II), a G to A transition at nucleotide
      position 20210, has recently been shown to be associated with the prothrombin
      plasma levels and the risk of both venous and arterial thrombosis. The purpose of
      this study was to investigate the prevalence of carriership of this mutation in
      various populations. We combined data from 11 centres in nine countries, where
      tests for this mutation had been performed in groups representing the general
      population. We calculated an overall prevalence estimate, by a precision-weighted
      method, and, since the distribution of the prevalences did not appear
      homogeneous, by an unweighted average of the prevalences. We examined differences
      in the prevalences by geographical location and ethnic background as a possible
      explanation for the heterogeneity. Among a total of 5527 individuals who had been
      tested, 111 heterozygous carriers of the 20210A mutation were found. The
      prevalence estimates varied from 0.7 to 4.0 between the centres. The overall
      prevalence estimate was 2.0 percent (CI95 1.4-2.6%). The variation around the
      summary estimate appeared more than was expected by chance alone, and this
      heterogeneity could be explained by geographic differences. In southern Europe,
      the prevalence was 3.0 percent (CI95 2.3 to 3.7%), nearly twice as high as the
      prevalence in northern Europe (1.7%, CI95 1.3 to 2.2%). The prothrombin variant
      appeared very rare in individuals from Asian and African descent. The 20210A
      prothrombin variant is a common abnormality, with a prevalence of carriership
      between one and four percent. It is more common in southern than in northern
      Europe. Since this distribution within Europe is very different to that of
      another prothrombotic mutation (factor V Leiden or factor V R506Q), founder
      effects are the most likely explanation for the geographical distribution of both
      mutations.

PMID- 9569178
TI  - Characterization of the genetic defects in recessive type 1 and type 3 von
      Willebrand disease patients of Italian origin.
AB  - The genetic defects causing recessive type 1 and type 3 von Willebrand disease
      (VWD) in eight families from the northern part of Italy have been investigated.
      Mutations were identified in 14 of the 16 disease-associated von Willebrand
      factor (VWF) genes. Only one mutation, a stop codon in exon 45, was previously
      reported. Several new mutations were identified: one cytosine insertion in exon
      42, one guanine deletion in exon 28, one probably complete VWF gene deletion, one
      substitution in the 3' splice site of intron 13, one possible gene conversion,
      and three candidate missense mutations. One missense mutation, the substitution
      of a cysteine in exon 42, was identified in all type 3 VWD patients that were
      previously characterized as a subgroup with significant increase of factor VIII
      procoagulant activity after desmopressin infusion. This paper demonstrates again
      that the molecular defects of quantitative VWD are diverse and located throughout
      the entire VWF gene.

PMID- 9569179
TI  - Ins405AsnPro mutation in the von Willebrand factor propeptide in recessive type
      2A (IIC) von Willebrand's disease.
AB  - The molecular defects of the von Willebrand factor (vWF) have been studied in the
      patient in whom the von Willebrand disease phenotype IIC was originally
      described. A six nucleotide insert, AATCCC, was found in exon 11 of the vWF gene,
      predicting the insertion of the amino acids asparagine and proline between
      phenylalanine 404 and threonine 405 of the vWF propeptide. The mutation was
      present in one allele. Analysis of amplification products derived from platelet
      vWF mRNA showed the other allele to be silent. The patient is thus a compound
      heterozygote for a null allele and the IIC allele, in accord with the recessive
      mode of inheritance of the IIC phenotype. Family studies indicated the IIC
      mutation to have occurred de novo, possibly as a result of a duplication event.
      In vitro mutagenesis and expression in COS-7 cells confirmed the detrimental
      effect of the mutation on vWF multimer assembly. Taken together with those of
      earlier studies the present findings suggest that the IIC phenotype may well be
      exclusively caused by mutations which result in changes of the amino acid
      sequence in certain regions of the vWF propeptide. Although in the recently
      revised classification of von Willebrand's disease variants, the IIC type is
      included in the 2A category, obviously it constitutes a very distinct subtype.

PMID- 9569180
TI  - Precise carrier diagnosis in families with haemophilia A: use of conformation
      sensitive gel electrophoresis for mutation screening and polymorphism analysis.
AB  - Causative mutations in the factor VIII gene of seven unrelated patients with
      severe haemophilia A were identified using the mutation screening procedure
      conformation sensitive gel electrophoresis (1) and characterised by direct
      sequencing. Female family members of all patients had requested either carrier
      status determination or prenatal diagnosis. However, lack of the factor VIII gene
      inversion, a prior family history or informative polymorphisms prevented
      diagnosis in these families. Identification of a mutation in each family enabled
      female carrier status to be determined in all cases. Six mutations were
      previously unreported. One Afro-Caribbean patient had two sequence changes; A670
      2G and A6769G. The latter, resulting in Met2238Val and previously reported as a
      FVIII mutation, was shown to be polymorphic with a 42% heterozygosity rate in an
      Afro-Caribbean population. Conformation sensitive gel electrophoresis was found
      to be technically simple and efficient at locating previously unknown FVIII gene
      mutations.

PMID- 9569181
TI  - The high prevalence of thermolabile 5-10 methylenetetrahydrofolate reductase
      (MTHFR) in Italians is not associated to an increased risk for coronary artery
      disease (CAD).
AB  - Mild hyperhomocysteinemia was found to be related to venous thrombosis,
      cerebrovascular and coronary artery disease (CAD). Some recent studies suggested
      that a mutation in the gene encoding for 5-10 methylenetetrahydrofolate reductase
      (MTHFR), due to a transition C-->T at nucleotide 677, is a genetic risk factor
      for vascular disease. However, several further studies could not confirm this
      association. We investigated 84 patients with CAD who underwent percutaneous
      transluminal coronary angioplasty (PTCA) and 106 healthy subjects. The prevalence
      of the mutated homozygous genotype was much higher than in other Italian
      populations, Europeans or other major human groups, but no excess of the Val/Val
      homozygotes was found in patients (28.5%) with respect to healthy subjects
      (30.2%). Mutated homozygous MTHFR genotype (+/+) was not found to be related to
      the clinical manifestations of CAD, to the prevalence of the common risk factors
      and to the rate of restenosis. In conclusion, thermolabile MTHFR does not appear
      to be associated "per se" with the risk for CAD or for restenosis after PTCA. The
      high frequency of the +/+ genotype in our Italian population (from Tuscany)
      confirms a wide macroheterogeneity and suggests a microheterogeneity in the
      genotype frequencies of the different ethnic populations.

PMID- 9569182
TI  - Polymorphism of platelet membrane glycoprotein IIIa: human platelet antigen 1b
      (HPA-1b/PlA2) is an inherited risk factor for premature myocardial infarction in
      coronary artery disease.
AB  - Conflicting results of an association between the human platelet antigen 1b (HPA
      1b or PlA2) allele and the risk of myocardial infarction and coronary artery
      disease have been reported. To assess the reason for this discrepancy, we
      determined the HPA-1 genotype in 298 men who had undergone coronary angiography,
      including 124 individuals with myocardial infarction, 83 individuals with
      coronary artery disease but no history of myocardial infarction, and 91 control
      patients. Among patients with acute or recent onset myocardial infarction (< 1
      year), the prevalence of HPA-1b was higher than among patients with coronary
      artery disease but without myocardial infarction (33 percent vs. 14 percent, p =
      0.016). In patients under 60 years of age this difference was even more
      pronounced (45 percent vs. 15 percent, p = 0.003). Unlike conventional risk
      factors HPA-1b does not represent a risk factor for coronary artery disease
      itself but appears to be associated with increased platelet thrombogenicity.

PMID- 9569183
TI  - Sex differences in coagulation and fibrinolysis in subjects with coronary artery
      disease.
AB  - Women with coronary artery disease (CAD) have a prognosis at least as bad and
      possibly worse than men. Differences in classical risk factors do not fully
      account for these findings and there is evidence that circulating levels of
      haemostatic factors may predict CAD risk. In this study sex differences in
      haemostatic risk factors were examined in relation to coronary stenosis. 609 (420
      men, 69%) subjects admitted for coronary angiography for suspected CAD were
      recruited. Levels of Factor VII:C (FVII:C), fibrinogen, plasminogen activator
      inhibitor-1 (PAI-1) and von Willebrand factor (vWF) were estimated in 296
      subjects from one centre. Of these, women (n = 107) had higher levels of FVII:C
      (134% vs 117%, p < 0.0005), and fibrinogen (3.4 g/l vs 3.2 g/l p = 0.01) than men
      (n = 189) and these differences remained after adjusting for other covariates. In
      subjects with angiographically significant atheroma these differences in
      haemostatic factors (n = 50 for women vs n = 147 for men) were exaggerated,
      (FVII:C 139% vs 117, p < 0.0001, fibrinogen 3.7 g/l vs 3.3 g/l p = 0.003), PAI-1
      (26.2 ng/ml vs 19.7 ng/ml, p = 0.02) with a trend towards higher levels of vWF in
      the women. Women with significant atheroma at angiography (n = 50) had higher
      levels of PAI-1 (25.0 ng/ml vs 13.4 ng/ml p < 0.0001) and vWF (1.25 IU/ml vs 1.06
      IU/ml, p = 0.02) and a trend towards higher levels of both fibrinogen and FVII:C
      than women with normal or in significant coronary vessel disease (n = 57).
      Elevated circulating levels of PAI-1, vWF, fibrinogen and FVII:C in women with
      angiographically proven CAD may contribute to an adverse cardiovascular risk
      factor profile and the poorer prognosis in females than male patients with proven
      coronary artery disease.

PMID- 9569184
TI  - Superficial vein thrombosis: incidence in association with pregnancy and
      prevalence of thrombophilic defects.
AB  - Superficial venous thrombotic (SVT) events are a feature of thrombophilic
      abnormalities, particularly those involving the protein C pathway. We have
      determined the incidence of SVT associated with pregnancy and the early
      postpartum period in a retrospective study involving 72000 deliveries. Fourty
      nine cases occurring in 47 individuals were recorded, with an overall incidence
      of 0.68/1000 deliveries (95% CI 0.48-0.88). None had a previous history of deep
      vein thrombosis or pulmonary embolism. Most events occurred in the early
      postpartum period (0.54/1000 deliveries). Twenty-four/fourty-seven were screened
      for established thrombophilic abnormalities, with only 1 abnormality detected
      (FV(Leiden) heterozygote). Thrombophilia may play a minor role in the aetiology
      of SVT associated with pregnancy, although a larger study is required to confirm
      this.

PMID- 9569185
TI  - Titration of antiplatelet treatment in pregnant women at risk of preeclampsia.
AB  - We recruited 111 patients who were considered to be at significantly increased
      risk of preeclampsia on the basis of previous obstetric history or preexisting
      medical disorders. All patients were treated with low dose aspirin (75 mg/day)
      from the first occasion the patient attended the antenatal clinic, regardless of
      gestational age. If the maternal mean platelet volume (MPV) increased
      significantly (by > 0.8 fl) from the baseline, antiplatelet treatment was
      increased. Five pregnancies were lost during the second trimester and 106 of the
      treated patients had live infants. The incidence of neonatal death (3/106
      infants) was much lower than in the previous pregnancies in these patients
      (32/134 infants). Patients who were treated from the first trimester of pregnancy
      (group A, 89 patients) did substantially better than those treated from the
      second trimester (group B, 17 patients) as assessed by the incidence of pre
      eclampsia or intrauterine growth restriction (IUGR), gestational age and
      birthweight at delivery. These data suggest that longitudinal monitoring of the
      MPV may identify the women who could benefit from increased antiplatelet
      treatment, and that antiplatelet treatment may be more effective when initiated
      in the first trimester rather than later in pregnancy.

PMID- 9569186
TI  - Increased thromboxane metabolites excretion in liver cirrhosis.
AB  - An augmented systemic production of thromboxane (TX) A2, as assessed by urinary
      excretion of the thromboxane metabolites, has been described in severe liver
      cirrhosis. However, the significance of this finding remains unclear since in
      liver cirrhosis a number of phenomena i.e. altered hepatic TXA2 metabolism,
      increased intrasplenic platelet destruction, may affect TXA2 entry into systemic
      circulation as well as its metabolism. In order to further clarify this, we
      measured both major enzymatic metabolites of TXB2 in the urine of 44 patients
      affected by liver cirrhosis, subdivided in three classes on the basis of Child
      Pugh criteria. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were assayed with
      previously validated RIA techniques. The urinary excretion rate of 11-dehydro
      TXB2 was significantly (p = 0.0001) increased in the cirrhotic patients (673.5
      pg/mg cr, median) in comparison with the controls (275 pg/mg cr, median) but no
      significant difference could be demonstrated among the excretion rates of the
      three patient subgroups. The excretion rate of 2,3 dinor-TXB2 was also
      significantly (p = 0.0001) increased in the patients (824 pg/mg cr, median) in
      comparison with controls (175 pg/mg cr, median), with a significant (p < 0.05)
      increase from class A (381 pg/mg cr) to class C (1337 pg/mg cr). The sum of the
      two enzymatic metabolites was significantly (p = 0.0001 ) increased in the
      cirrhotic patients in comparison to controls, with a progressive increase from
      class A (1003 pg/mg cr, median) to class C (2240 pg/mg cr, median). The urinary
      excretion of 2,3 dinor-TXB2 was significantly (p = 0.008) related to plasma
      prothrombin fragment 1+2 (F1+2). This study provides further evidence of
      increased thromboxane biosynthesis in liver cirrhosis. Moreover, we demonstrate
      intraliver shift of thromboxane metabolic disposition, due to progressive liver
      decompensation, because only the fraction undergoing beta-oxidation to 2,3-dinor
      TXB2 was progressively increased with the degree of liver failure. We, also, find
      a significant correlation between urinary excretion of 2,3-dinor-TXB2 and plasma
      F1+2, suggesting that clotting activation could partly account for in vivo
      platelet activation.

PMID- 9569187
TI  - Anti-hepatitis G E2 antibody detection and its relation to serum HGV-RNA in
      patients with clotting disorders: high prevalence of HGV infection and
      spontaneous remission.
AB  - In a previous study, we have determined the prevalence of serum HGV-RNA in
      patients with congenital clotting disorders. Twenty-six (15%) of 175 patients
      investigated were serum HGV-RNA positive. In addition, HGV-RNA was detectable in
      peripheral blood mononuclear cells (PBMC) in ten percent of the cases, three of
      these patients were serum HGV-RNA negative. In the present study, we have
      determined the prevalence of anti-HGV-E2 antibodies in the same patient
      population. Anti-HGV-E2 as determined by ELISA was detected in 45 patients
      (25.7%). Forty of these patients were serum HGV-RNA negative. Ninety-two percent
      of the 26 HGV viremic patients and all but one patient (44 patients) with
      detectable anti-HGV-E2 had coinfection with the hepatitis C virus (HCV). Of these
      coinfected patients, 62.5% of HGV viremic patients and 53% of anti-HGV-E2
      positive patients showed elevated serum ALT levels. Anti-HGV-E2 seroconversion is
      thus not associated with HCV infection. Two patients who were solely infected
      with HGV had normal serum ALT levels. In a retrospective longitudinal study, we
      have observed in 15 patients that serum HGV-RNA persisted during one to 19 years
      of follow-up, while anti-HGV-E2 was repeatedly negative. Five additional patients
      who were anti-HGV-E2 positive with concomitant detectable HGV-RNA (4 patients in
      serum and 1 patient in PBMC) became HGV-RNA negative during follow-up, ranging
      from 1 to 8 years after the first detection of anti-HGV-E2 antibodies. Two
      patients had lost anti-HGV-E2 antibodies 3 to 6 years after the seroconversion
      without the re-appearance of serum HGV-RNA. From these findings, it is clear that
      the prevalence rate of HGV infection in patients with clotting disorders as
      determined by PCR assay for HGV-RNA and anti-HGV-E2 by ELISA is actually higher
      than the prevalence of HGV viremia. Although HGV viremia may persist for longer
      than 19 years, most of the patients infected with HGV may clear the viremia
      spontaneously. The clearance of viremia is usually associated with seroconversion
      to anti-HGV-E2. In addition, anti-HGV-E2 may be lost during years of follow-up
      without the reappearance of the HGV-RNA. Although HGV infection does not seem to
      influence the fate of HCV infection and does not induce increased levels of serum
      ALT, the clinical significance of long-term infection remains to be established.

PMID- 9569188
TI  - Homozygous protein C deficiency: description of a new mutation and successful
      treatment with low molecular weight heparin.
AB  - We present a kindred with a new mutation of the protein C gene, in which the
      proband had an unusual clinical presentation. The relationship between warfarin
      induced skin necrosis and level of anticoagulation was investigated. The
      pharmacokinetics of protein C concentrate was assessed to determine frequency of
      replacement therapy. The clinical and biochemical efficacy of therapy with low
      molecular weight heparin (LMWH) was assessed. The effect of long-term LMWH on
      bone density in the growing child was monitored using whole body densitometry.
      Warfarin therapy required an INR of greater than 3.5 to avoid skin necrosis. If
      protein C replacement was to be used, doses of 100 U/kg/day would have been
      required to maintain protein C levels consistently at or above 0.20 U/ml. While
      receiving prophylactic therapy with LMWH for almost 3 years, there were no
      episodes of recurrent thrombosis, no skin necrosis and no bleeding. Biochemical
      markers of in vivo thrombin generation were suppressed and within the normal
      range. Bone density continued to increase at the normal rate throughout the
      treatment period. LMWH is an effective form of long-term therapy for homozygous
      protein C deficient patients with measurable protein C levels.

PMID- 9569190
TI  - A new direct, fast and quantitative enzyme-linked ligandsorbent assay for
      measurement of free protein S antigen.
AB  - A new method to determine the concentration of free protein S in plasma is
      described. It is an enzyme-linked ligandsorbent assay (ELSA) which utilises the
      protein S binding capacity of the natural ligand C4b-binding protein (C4BP) to
      capture the free protein S from plasma samples. The use of C4BP as ligand in the
      assay is possible due to the high affinity (Kd = 0.1 nM) of the interaction
      between protein S and C4BP and to a slow rate of complex dissociation. A
      monoclonal antibody (HPS 54) was conjugated with horseradish peroxidase and used
      as target antibody. This antibody recognises a Ca2+ dependent epitope in the
      first EGF-like domain of protein S and does not interfere with C4BP binding sites
      of protein S. Addition of calcium in the assay helped prevent dissociation of the
      C4BP-protein S-HPS 54 complex. Three different experiments demonstrated the assay
      to be specific for free protein S. First, near-identical dose response curves
      were obtained with protein S in plasma and with purified protein S. Second,
      addition of purified C4BP to normal plasma resulted in loss of free protein S.
      Third, protein S depleted plasma gave zero values and around 80% of purified
      protein S added to protein S depleted plasma, and approximately 70% of protein S
      added to protein S deficient plasma samples, was recovered with the assay. The
      assay is fast (involves only a single incubation step of 30 min), sensitive and
      the range of measurement is 3% to 200% of free protein S when plasma dilution
      1:20 represents 100%. Intra- and inter-assay coefficients of variation at two
      levels were 2.3-4.3% and 5.1-7.4%, respectively. In a large protein S deficient
      family, the assay showed 100% sensitivity and specificity for the causative
      mutation. Moreover, free protein S levels in anticoagulated protein S deficient
      patients were completely separated from those obtained in non-anticoagulated
      controls. The new assay for free protein S is suitable for automation and it
      provides a useful means for routine clinical purposes to detect protein S
      deficiencies.

PMID- 9569189
TI  - Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK
      Haemophilia Centre Directors Organisation.
AB  - Twenty six patients with mild or moderate haemophilia A and inhibitors are
      described. The inhibitor was detected at a median age of 33 years, after a median
      of 5.5 bleeding episodes. This usually following intensive replacement therapy.
      The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45
      BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to
      0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding
      in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was
      often severe and caused two deaths. The inhibitor disappeared spontaneously, or
      following immune tolerance induction, in 16 cases after a median of 9 months
      (range 0.5-46), with a return to the original baseline VIIIC level and bleeding
      pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of
      the cases over a median period of 99 months (range 17-433 months) of follow-up.
      Inhibitors are an uncommon complication of mild haemophilia which frequently
      persist and may be associated with severe, life-threatening, haemorrhage. Forty
      one percent of treated haemophilic family members had a history of factor VIII
      inhibitors, suggesting a familial predisposition to develop inhibitors in these
      kindreds. Sixteen patients from 11 families were genotyped. Seven different
      missense mutations affecting the light chain were detected and two in the A2
      domain. Five patients from three families had a mutation causing a substitution
      of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor
      formation since 7 of the 18 affected individuals have a history of inhibitor
      development.

PMID- 9569191
TI  - Simple and reliable factor V genotyping by PNA-mediated PCR clamping.
AB  - Resistance to activated protein C (APC resistance) is the most common cause of
      thrombophilia and linked to a single point mutation in the factor V gene (G-->A
      transition at nucleotide 1691). In the past, several PCR based methods have been
      proposed to determine the allelostatus of individual patients from small amounts
      of blood DNA including PCR followed by restriction fragment length polymorphism
      detection (PCR-RFLP), PCR using sequence-specific primers (PCR-SSP) and
      oligonucleotide ligation assay (OLA). Here, we present a novel approach based on
      the method of peptide nucleic acid(PNA)-mediated PCR clamping which is extremely
      sensitive to base pair mismatches. If PNAs specific for the two allelic variants
      are applied separately in each case a clear discrimination between a heterozygous
      or homozygous normal or homozygous Factor V Leiden status is possible and no
      further confirmation step is required. In a prospective study, 60 patients with
      suspected venous thrombosis events were tested and compared to the conventional
      PCR-RFLP technique. The concordance between both methods was 100%. PNA-based
      factor V genotyping, therefore, should be considered for large scale screening of
      those patients considered to be at risk for deep venous thrombosis.

PMID- 9569192
TI  - High sensitivity detection of activated factor IX: application to the analysis of
      different therapeutical factor IX concentrates and prothrombin complexes.
AB  - A very sensitive and highly reliable test system for the detection of activated
      coagulation factor IX (FIXa) has been established. This assay system is based on
      the cleavage of a fluorogenic substrate by activated factor X (FXa) which is
      generated by FIXa. This assay can be used to process a large number of samples at
      a time and, being based on the convenient microtiter plate format, can easily be
      adapted to automated processing for routine screening of large sample numbers.
      With this assay at hand we determined the FIXa content of different commercially
      available therapeutic FIX sources, such as high purity FIX (HPFIX) and
      prothrombin complex concentrates (PCC). Here we demonstrate that PCC from several
      suppliers do not contain significantly higher levels of FIXa as compared to HPFIX
      from the same supplier. In fact, there is a tendency for HPFIX to contain more
      FIXa than PCC. Moreover, HPFIX from certain manufacturers who do not produce PCC
      are characterized by an exceptionally high content of FIXa. Therefore, the higher
      thrombogenic potential of PCC which is well documented clinically cannot be
      explained solely -- if at all -- by an increased content of FIXa. Rather, it will
      be necessary to identify other components responsible for this phenomenon.

PMID- 9569193
TI  - Weight-loss induced changes in plasma factor VII coagulant activity and relation
      to the factor VII Arg/Gln353 polymorphism in moderately obese adults.
AB  - Elevated plasma factor VII coagulant activity (factor VIIc) may be an independent
      risk factor for coronary heart disease. Several cross-sectional studies suggest
      that a polymorphism of the factor VII gene (Arg-Gln353) interacts with plasma
      triglyceride level in determining factor VIIc, but prospective data are lacking.
      Factor VII genotype, factor VIIc, and triglyceride level were measured in
      moderately obese adults aged 25 to 45 who underwent a six-month clinical trial to
      evaluate strategies for weight loss. A total of 48 men and 50 women who
      experienced substantial weight loss (mean: 10 kg) provided samples for genetic
      analysis. Overall, 78% of participants were homozygous for the Arg353 allele,
      while the remaining 22% were heterozygous (Arg/Gln353). At the baseline
      examination, heterozygotes had lower mean factor VIIc than Arg353 homozygotes
      (92% vs. 112%; p<0.001), and genotype explained 18% of the variance of factor
      VIIc. Average six-month weight loss was similar in both genotypes; mean
      reductions in factor VIIc following weight loss were greatest among Arg353
      homozygotes with high initial values (> 120%). Cross-sectional and longitudinal
      associations between plasma factor VIIc and triglyceride level were not dependent
      on genotype. These data confirm that the Gln353 allele is associated with lower
      factor VII coagulant activity in moderately obese adults, but they do not support
      the hypothesis that the Arg-Gln353 polymorphism interacts with plasma
      triglyceride level in determining factor VIIc.

PMID- 9569194
TI  - The contribution of anti-prothrombin-antibodies to lupus anticoagulant activity-
      discrimination between functional and non-functional anti-prothrombin-antibodies.
AB  - The presence of lupus anticoagulant (LAC) is strongly correlated with a history
      of thrombosis in patients with SLE. LAC activity can be caused by anti
      prothrombin (FII)- and/or anti-beta2glycoprotein I (beta2GPI)-antibodies. In the
      present study, the contribution of anti-FII-antibodies to LAC activity was
      measured in 28 LAC positive plasmas. Plasmas were incubated with prothrombin or
      BSA, immobilized on CNBr-activated Sepharose, to absorb all anti-FII-antibodies.
      In 4 out of the 28 plasmas LAC activity was completely dependent on anti-FII
      antibodies. In 7 out of the 28 plasmas, anti-FII-antibodies did not contribute to
      LAC activity. These anti-FII-antibodies can be regarded as non-functional
      antibodies. In the majority (17/28) of the samples, LAC activity within a single
      plasma was caused by a combination of antibodies with different specificities.
      Both dRVVT and KCT showed comparable sensitivity for the detection of functional
      anti-FII-antibodies. In conclusion, in most samples LAC activity is not caused by
      anti-FII-antibodies alone but by a combination of different types of antibodies.
      The presence of LAC activity and anti-FII-antibodies in one plasma does not
      automatically implicate that these antibodies are responsible for the LAC
      activity.

PMID- 9569195
TI  - Evaluation of the factors contributing to fibrin-dependent plasminogen
      activation.
AB  - Polymerized fibrin strongly enhances tissue plasminogen activator (tPA)-mediated
      plasminogen activation, concomitant with exposure of 'fibrin-specific' epitopes
      at 'Aalpha148-160' and 'gamma312-324'. To investigate which aspects of
      polymerization are involved in these activities, we explored the fibrin
      polymerization process by evaluating the ability of factor XIIIa-crosslinked
      fibrinogen polymers to expose 'fibrin-specific' epitopes and enhance plasminogen
      activation. Crosslinked normal fibrinogen, fibrinogen with deficient [des Bbeta1
      42] or defective [Birmingham (AalphaR16H)] fibrin 'D:E' assembly sites ('E(A)'),
      or with defective end-to-end self-association sites ('D:D') [Cedar Rapids
      (gammaR275C)], exposed both 'fibrin-specific' epitopes and enhanced tPA-dependent
      plasminogen activation, whereas non-crosslinked fibrinogens showed minimal or no
      such activities. Epitope expression in crosslinked fibrinogen was retained in the
      presence of the fibrin E(A) site peptide homolog, gly-pro-arg-pro (GPRP), which
      inhibits fibrin D:E association, except for the Aalpha148-160 epitope in des
      Bbeta1-42 fibrinogen, which was not expressed. Fibrin prepared from crosslinked
      normal or abnormal fibrinogen, except for the des Bbeta1-42 fibrin epitopes,
      which were reduced or absent, expressed 'fibrin-specific' epitopes even in the
      presence of GPRP, which otherwise impairs such expression in non-crosslinked
      fibrin. Epitope exposure in fibrin prepared from non-crosslinked fibrinogen was
      nearly normal in Cedar Rapids fibrin (heterozygous D:D defect), but reduced in
      Birmingham fibrin (heterozygous E(A) defect), nil in des Bbeta1-42 fibrin (E(A)
      deficient), and absent in all cases in the presence of GPRP. In contrast,
      plasminogen activation stimulatory activity that had been exposed in crosslinked
      normal fibrinogen or in crosslinked des Bbeta1-42 or Cedar Rapids fibrin, was
      preserved to a large extent in the presence of GPRP, suggesting that once
      enhanced stimulatory activity and epitopes are exposed, they are not completely
      reversible. The findings indicate that end-to-end intermolecular associations
      (D:D) are not critical for 'fibrin-specific' epitope exposure, but that
      polymerization brought about in fibrinogen through factor XIIIa crosslinking, or
      in fibrin through 'D:E' interactions, is necessary for 'fibrin-specific' (more
      correctly, 'polymerization-specific') epitope exposure and enhancement of
      plasminogen activation.

PMID- 9569196
TI  - A common 4G allele in the promoter of the plasminogen activator inhibitor-1 (PAI
      1) gene as a risk factor for pulmonary embolism and arterial thrombosis in
      hereditary protein S deficiency.
AB  - Reduced fibrinolytic capacity due to increased plasminogen activator inhibitor-1
      (PAI-1) activity in plasma is a common finding in patients with coronary heart
      disease or venous thromboembolism, although its clinical significance is debated.
      Recently, a dimorphism in the PAI-1 promoter (4G-5G) has been reported and
      homozygosity for the 4G allele is associated with increased transcription and
      higher PAI-1 levels. Homozygous 4G genotype has been suggested to be a risk
      factor for myocardial infarction. In the present study, the 4G-5G dimorphism was
      determined in 349 individuals from 21 thrombophilic families with hereditary
      protein S deficiency and in 140 unrelated healthy controls. Among the 143 protein
      S deficient individuals, there was no relationship between deep or superficial
      venous thrombosis and the PAI-1 dimorphism. However, 26% (12/46) of individuals
      having protein S deficiency combined with homozygosity for the 4G allele had
      suffered pulmonary embolism as compared to 7% (7/97) of protein S deficient
      individuals carrying at least one 5G allele (p = 0.0019). In protein S deficient
      individuals, arterial thrombosis was found to be associated with smoking and 4G
      homozygosity. No association was found between the PAI-1 dimorphism and arterial
      or venous thromboembolism in family members without protein S deficiency. In
      conclusion, the PAI-1 genotype affects the phenotypic expression of thrombophilia
      in protein S deficient individuals.

PMID- 9569197
TI  - Monoclonal antibody-based immunoassays for the specific quantitation of rat PAI-1
      antigen and activity in biological samples.
AB  - Two enzyme-linked immunosorbent assays (ELISAs) for the quantitation of rat
      plasminogen activator inhibitor-1 (PAI-1) antigen and activity, respectively, in
      biological fluids were developed using monoclonal antibodies raised against
      recombinant rat PAI-1. These assays had a lower limit of sensitivity in plasma of
      0.3 and 0.15 ng/ml, respectively. The intra-assay, inter-assay and inter-dilution
      coefficients of variation were 9, 14 and 9%, respectively, for the antigen assay
      and 8, 17 and 13%, respectively for the activity assay. Assay recoveries of
      recombinant rat PAI-1 (5 to 20 ng/ml) added to plasma were 73 to 88% and 89 to
      93% for the antigen and the activity assay, respectively. The level of PAI-1
      antigen in rat plasma was 1.8 +/- 0.9 ng/ml (mean +/- SD, n = 18), with a
      corresponding value of 1.0 +/- 0.5 ng/ml for PAI-1 activity. In lysed platelet
      rich rat plasma PAI-1 antigen was 6.0 +/- 1.0 ng/ml (n = 8) and PAI-1 activity
      was 2.3 +/- 0.4 ng/ml (n = 8). Endotoxin injection (0.5 mg/kg) induced a time
      dependent increase of both PAI-1 antigen and PAI-1 activity levels in rat plasma.
      eventually resulting in a 100- to 200-fold increase (p < 0.0001 vs. baseline). A
      linear correlation was found between PAI-1 antigen and activity levels in normal
      plasma (r = 0.63, n = 18, p < 0.01) and in plasma from endotoxin-treated rats (r
      = 0.90, n = 35, p < 0.001). Application of these assays for the analysis of gel
      filtration experiments of plasma from endotoxin-treated rats demonstrated that
      PAI-1 antigen eluted as two peaks (with corresponding Mr of approximately 430 kDa
      and 61 kDa) whereas PAI-1 activity eluted as a single peak corresponding with the
      high molecular weight antigen form. Thus, these unique assays allowing the
      specific determination of rat PAI-1 antigen and rat PAI-1 activity may constitute
      important tools for further investigations on the pathophysiological role of PAI
      1 in a variety of experimental rat models.

PMID- 9569198
TI  - The distribution of the secreted and intracellular forms of plasminogen activator
      inhibitor 2 (PAI-2) in human peripheral blood monocytes is modulated by serum.
AB  - Plasminogen activator inhibitor 2 (PAI-2) is produced by activated monocytes in
      two forms, intracellular and secreted. We have studied the distribution of these
      two forms in unstimulated human peripheral blood monocytes and after stimulation
      by thrombin. Fetal calf serum (FCS) in the culture medium was absolutely
      necessary for accumulation of intracellular PAI-2; but not for synthesis and
      secretion. Even at a concentration as low as 0.1%, FCS restored accumulation of
      intracellular PAI-2. Increasing concentrations of FCS resulted in an increase in
      the ratio of intracellular to secreted PAI-2. The factor that promoted
      accumulation of intracellular PAI-2 was not a platelet product. Failure of
      monocytes to accumulate PAI-2 did not reflect leakage due to cell death, as
      assessed by LDH in culture supernatants. We propose that accumulation of
      intracellular PAI-2 is not simply due to poor secretion, but is an active process
      that is modulated by factor(s) found in serum.

PMID- 9569199
TI  - Fibrinogen coating density affects the conformation of immobilized fibrinogen:
      implications for platelet adhesion and spreading.
AB  - Adhesion of platelets to immobilized fibrinogen appears to play an important role
      in a variety of physiologic and pathologic phenomena. We previously observed that
      the fibrinogen concentration used to coat polystyrene wells affected the
      morphology and distribution of GP IIb/IIIa receptors on the surface of platelets
      adherent to the fibrinogen. One possible explanation for these differences is
      that fibrinogen immobilized at high density adopts a different conformation than
      fibrinogen immobilized at low density. To address this possibility, we studied
      the binding of a panel of anti-fibrinogen monoclonal antibodies (mAbs) to
      fibrinogen immobilized at different coating densities. Three different patterns
      of binding were observed: 1) a linear increase in binding to wells coated with 1
      10 microg/ml fibrinogen, followed by a lesser increase or plateau at higher
      fibrinogen concentrations (mAbs Fd4-4E1, Fd4-7B3, 1D4, 4-2); 2) minimal
      reactivity at all fibrinogen concentrations (mAbs GC4-1A12, 2C34); 3) a biphasic
      response, with a linear increase up to 10 microg/ml fibrinogen and then a
      significant decline in binding at higher fibrinogen concentrations (mAbs 311,
      31A9, FPA 19/7, 9C3, 1C5-A5/2, 44-3). The patterns of mAb binding to fibrinogen
      immobilized from plasma were similar. Most mAbs that demonstrated a biphasic
      response bound poorly or not at all to soluble fibrinogen, while mAbs that
      demonstrated a linear/plateau response were able to bind soluble fibrinogen. At
      equal surface densities, mAbs that bound biphasically, particularly mAb 1C5-A5/2,
      were more reactive to urea-denatured than native fibrinogen. mAbs 1C5-A5/2 and 44
      3 are specific for gamma 1-78 and 95-265, respectively, suggesting that the
      fibrinogen gamma-chain may be sensitive to changes in conformation induced by
      immobilization. In summary, these data suggest that fibrinogen immobilized at 1
      10 microg/ml adopts a conformation unlike soluble fibrinogen, while fibrinogen
      immobilized at > 30 microg/ml adopts a more solution-like conformation. These
      differences in fibrinogen conformation may partially account for the ability of
      platelets to bind to immobilized fibrinogen without the addition of agonist, as
      well as the differences in spreading and GPIIb/IIIa distribution on platelets
      adherent to high- versus low-density immobilized fibrinogen.

PMID- 9569200
TI  - Rap1b association with the platelet cytoskeleton occurs in the absence of
      glycoproteins IIb/IIIa.
AB  - Platelet membrane glycoproteins (GP) IIb/IIa and rap1b, a 21 kDa GTP binding
      protein, associate with the triton-insoluble, activation-dependent platelet
      cytoskeleton with similar rates and divalent cation requirement. To examine the
      possibility that GPIIb/IIIa was required for rap1b association with the
      cytoskeleton, experiments were performed to determine if the two proteins were
      linked under various conditions. Chromatography of lysates from resting platelets
      on Sephacryl S-300 showed that GPIIb/IIIa and rap1b were well separated and
      distinct proteins. Immunoprecipitation of GPIIb/IIIa from lysates of resting
      platelets did not produce rap1b or other low molecular weight GTP binding
      proteins and immunoprecipitation of rap1b from lysates of resting platelets did
      not produce GPIIb/IIIa. Finally, rap1b was associated with the activation
      dependent cytoskeleton of platelets from a patient with Glanzmann's
      thrombasthenia who lacks surface expressed glycoproteins IIb and IIIa. Based on
      these findings, we conclude that no association between GPIIb/IIIa and raplb is
      found in resting platelets and that rap1b association with the activation
      dependent cytoskeleton is at least partly independent of GPIIb/IIIa.

PMID- 9569201
TI  - Relations of platelet Ca2+ handling and membrane microviscosity to vascular tone
      and restenosis after angioplasty in human coronary artery.
AB  - This study was designed to assess whether platelet Ca2+ handling or membrane
      microviscosity could be considered as indexes of vascular tone, or could help to
      predict an increased risk of restenosis after coronary angioplasty. Vascular tone
      was quantified in 21 patients with stable angina by the vasodilator response to
      sin-1 intracoronary injection in the reference coronary segment and by the
      importance of the acute recoil after angioplasty in the narrowed segment. The
      degree of restenosis was quantified by coronary angiography 6 months later.
      Individual values of relative sin-1-induced changes in the reference coronary
      diameter were positively correlated with cytosolic Ca2+ concentration in
      unstimulated platelets, irrespective of the extracellular Ca2+ concentration (p <
      0.01). This relationship was also observed with the thrombin-evoked Ca2+ changes,
      measured in the absence of a Ca2+ influx (p = 0.01). No relationship was found
      between sin-1-induced coronary changes and membrane microviscosity evaluated by
      TMA-DPH and DPH anisotropies or platelet volume, or between degree of acute
      recoil and platelet characteristics. In conclusion, platelet Ca2+ reflects the
      vasodilating efficacy in response to sin-1, but cannot help to predict restenosis
      after coronary angioplasty.

PMID- 9569202
TI  - Effects of skin mast cells on bleeding time and coagulation activation at the
      site of platelet plug formation.
AB  - We studied the effects of stimulated skin mast cells on bleeding time and
      thrombin generation which was measured using prothrombin fragment F 1+2 (F 1+2)
      and thrombin-antithrombin-III-complex (TAT). In 10 patients with urticaria
      pigmentosa (chronic cutaneous mast cell accumulation) the mean bleeding time was
      significantly prolonged in wounds made on urticaria pigmentosa lesions vs. normal
      skin (460 +/- 34 vs. 342 +/- 27 s, p = 0.005). In 10 atopic subjects skin
      incisions were made on prick-tested sites 30, 60, 120 and 240 min after
      administration of an allergen (acute mast cell stimulation), histamine or
      vehicle. The mean bleeding time was significantly prolonged at all time points,
      being maximal at 120 min (60% prolonged) in wounds made on allergen-stimulated
      skin areas (p < 0.01) compared with histamine or vehicle sites. Administration of
      allergen or histamine lowered the TAT concentration in the bleeding-time blood.
      Furthermore, TAT and F 1+2 levels in the bleeding-time blood were lower at 60,
      120 and 240 min after allergen or histamine application in comparison with
      samples collected at 30 min. We conclude that skin mast cells can regulate
      primary hemostasis by prolonging bleeding time and by inhibiting thrombin
      generation.

PMID- 9569203
TI  - Thrombomodulin modulates the mitogenic response to thrombin of human umbilical
      vein endothelial cells.
AB  - Thrombin interacts with its receptor and thrombomodulin on endothelial cells. We
      evaluated the respective roles of these two proteins on human umbilical vein
      endothelial cell (HUVEC) growth by comparing thrombin, S195A (a mutant thrombin
      in which the serine of the charge stabilizing system had been replaced by
      alanine), and the receptor activating peptide (TRAP). Thrombin and TRAP induced
      DNA synthesis (half maximal cell proliferation with 5 nM and 25 microM,
      respectively), whereas S195A thrombin was inactive, inferring that growth is
      mediated through the thrombin receptor. Surprisingly, cells stimulated by TRAP
      exhibited a maximal proliferation twice greater than that obtained with thrombin.
      Combination of thrombin and TRAP resulted in a mitogenic response higher than by
      thrombin alone, but lower than by TRAP alone. The role of thrombomodulin was
      evaluated by adding an anti-thrombomodulin antibody, which prevents formation of
      the thrombin-thrombomodulin complex. Antibody did not interfere with cell
      proliferation induced by TRAP, but enhanced that induced by thrombin. We conclude
      that formation of the thrombin-thrombomodulin complex restrains HUVEC
      proliferation mediated through the thrombin receptor.

PMID- 9569204
TI  - Adenosine 3':5'-cyclic monophosphate induces regulated secretion of tissue-type
      plasminogen activator and von Willebrand factor from cultured human endothelial
      cells.
AB  - The effect of compounds increasing intracellular adenosine 3':5'-cyclic
      monophosphate [cAMP]i levels (prostacyclin, isoproterenol, forskolin, cholera
      toxin), and of the cAMP analogs 8-bromo-cAMP and dibutyryl-cAMP, on the regulated
      secretion (acute release) of tissue-type plasminogen activator (tPA) and von
      Willebrand factor (vWF) was studied in cultured human umbilical vein endothelial
      cells (HUVEC). Prostacyclin, isoproterenol and forskolin, which increased [cAMP]i
      in HUVEC, and the cell-permeant cAMP analog 8-bromo-cAMP induced dose- and time
      dependent secretion of tPA and vWF. The extent of vWF and tPA release correlated
      with [cAMP]i, and was increased by the phosphodiesterase inhibitor
      isobutylmethylxanthine. In contrast to thrombin, the cAMP-elevating agents did
      not increase the intracellular calcium concentration [Ca2+]i in HUVEC. At
      submaximal concentrations, the effects of thrombin and prostacyclin were
      additive. Our results show that an increase in [cAMP]i resulted in regulated
      secretion (acute release) of tPA and vWF from HUVEC, without the concomitant
      increase in [Ca2+]i which is, in HUVEC, essential for thrombin-induced regulated
      secretion to occur. cAMP-induced secretion represents a novel mechanism for
      causing regulated secretion of tPA and vWF from endothelial cells.

PMID- 9569205
TI  - Effect of a synthetic factor Xa inhibitor, YM-60828, on blood vessel patency in
      combination with a thrombolytic agent and on blood loss from the operation site
      in a rat model of arterial thrombosis.
AB  - We examined the adjunctive effect of a novel factor Xa inhibitor, YM-60828, on
      vessel patency and blood loss from the operation site after successful
      thrombolysis with a modified tissue-type plasminogen activator (moPA) in an
      electrically-induced carotid artery thrombosis model in rats. Five minutes after
      the induction of occlusive thrombus, a test drug (YM-60828, argatroban, heparin
      or saline) was administered by i.v. bolus injection followed by continuous
      infusion. Thrombolysis was induced with moPA by i.v. bolus injection at a dose of
      650,000 IU/ kg. YM-60828 at 1 mg/kg i.v. followed by 3 mg/kg/h significantly
      prevented reocclusion, increased the duration of patency, and improved vessel
      patency after successful thrombolysis without any significant increase in blood
      loss from the operation site. Argatroban at 1 mg/kg i.v. followed by 3 mg/kg/h
      and heparin at 300 U/kg i.v. followed by 150 U/kg/h also significantly improved
      these parameters, but were accompanied by a significant increase in blood loss.
      These results suggest that the factor Xa inhibitor YM-60828 may be a potent and
      useful adjunctive agent with a lower risk of bleeding complications than
      argatroban and heparin in thrombolytic therapy.

PMID- 9569206
TI  - Multiple inhibition of platelet activation by aurintricarboxylic acid prevents
      vascular stenosis after endothelial injury in hamster carotid artery.
AB  - Activated platelets are instrumental in restenosis due to their role in thrombus
      formation. Aurintricarboxylic acid (ATA) has been reported to prevent platelet
      activation by inhibiting von Willebrand factor binding to platelet glycoprotein
      (GP)Ib. We investigated the effects of ATA in vitro and in vivo in hamsters. ATA
      inhibited the in vitro platelet aggregation induced by ADP, botrocetin and
      thrombin, but not by collagen. The IC50 values during the ex vivo platelet
      aggregation by ADP, botrocetin and thrombin were 8.2 +/- 1.8 microM, 0.9 +/- 0.4
      microg/ml and 2.4 +/- 0.8 unit/ml, respectively. The platelet retention time to
      collagen-coated beads of hamster blood samples was inhibited by ATA (0.1, 0.3 and
      1.0 mg/kg per hour) in a dose-dependent manner. Continuous administration of ATA
      (0, 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg per h) via an infusion pump produced dose
      dependent antithrombotic effects: the time to occlude the carotid artery after
      vascular injury with a modified catheter was prolonged. Only when infused at
      doses of 3.0 and 10.0 mg/kg per hour, bleeding times were significantly
      prolonged. The continuous treatment with ATA (1.0 mg/kg per h) using a 2ML1 Alzet
      infusion pump for 2 weeks, resulted in a decrease in neointimal area by 22.2 +/-
      6.8% when measured 2 weeks after injury induction. DNA synthesis using DDT1MF2
      hamster SMCs was decreased by ATA in a dose-dependent manner. ATA reduced the
      number of platelets adhering on the injured area, as detected by electron
      microscopy. These results indicated that treatment with ATA inhibited platelet
      adhesion but also SMC proliferation. These observations may explain the effect of
      ATA on neointima formation.

PMID- 9569207
TI  - A detailed comparison of the performance of the standard versus the Nijmegen
      modification of the Bethesda assay in detecting factor VIII:C inhibitors in the
      haemophilia A population of Canada. Association of Hemophilia Centre Directors of
      Canada. Factor VIII/IX Subcommittee of Scientific and Standardization Committee
      of International Society on Thrombosis and Haemostasis.
AB  - The Bethesda assay is widely used to monitor the development and progress of
      Factor VIII:C inhibitors. Factor VIII stability in the substrate plasma (normal
      pool) is compromised by pH shift and reduction in protein concentration.
      Preliminary study, by Verbruggen and colleagues (8), suggested a reduction in
      spuriously positive assay results may result from buffering the normal pool
      plasma substrate with imidazole to pH 7.4 and substituting Factor VIII deficient
      plasma for imidazole buffer in the control incubation mix. These laboratory
      findings have now been confirmed by the performance of both the standard and the
      modified Bethesda assays in parallel on 877 patient samples screened during the
      Factor VIII:C Inhibitor Surveillance Program instituted following the conversion
      of all Canadian haemophilia A patients to recombinant Factor VIII. Although this
      study does not address the question of the clinical significance of spurious
      positive assays, these laboratory findings do support the conclusions of
      Verbruggen and the modified assay has recently been endorsed by the Factor
      VIII/IX Subcommittee of the SSC.

PMID- 9569208
TI  - Expression of the factor VII activating protease, hepsin, in situ in renal cell
      carcinoma.

PMID- 9569209
TI  - Apo E4/3-rich remnant lipoproteins and platelet aggregation: a case report.

PMID- 9569210
TI  - Reduced protein C levels--a contributory factor for stroke in sickle cell
      disease.

PMID- 9569211
TI  - Intron 22 inversions in factor VIII gene in Indian hemophiliacs.

PMID- 9569212
TI  - Absence of prothrombin mutation in Inuit (Greenland Eskimos)

PMID- 9569213
TI  - Frequency of factor V (FV) Leiden and C677T methylenetetrahydrofolate reductase
      (MTHFR) mutations in Colombians.

PMID- 9569214
TI  - What is the Tasman trial?

PMID- 9569215
TI  - Health promotion and managed care: surveys of California's health plans and
      population.
AB  - INTRODUCTION: The purpose was to examine whether health-promotion programs
      offered by California health plans are a serious attempt to improve health status
      or a marketing device used in an increasingly competitive marketplace. The
      research examined differences in the coverage, availability, utilization, and
      evaluation of health-promotion programs in California health plans. METHODS: A
      mail survey was done of the 35 HMOs (86% response) and 18 health insurance
      carriers (83% response) licensed to sell comprehensive health insurance in
      California in 1996 (some plans sell both HMO and PPO/indemnity products). The
      final sample included 30 commercial HMOs and 20 PPO and indemnity plans. The 1996
      California Behavioral Risk Factor Survey (BRFS) of 4,000 adults was used to
      estimate population participation rates in health-promotion programs. RESULTS:
      California's HMOs in 1996 offered more comprehensive preventive benefits and
      health-promotion programs compared to PPO and indemnity plans. HMOs relied on a
      more comprehensive set of health-education methods to communicate health
      information to members and were more likely to open their programs to the public.
      HMOs are also more likely to have developed relationships with community-based
      and public health providers. Participation in health-promotion programs is low
      (2%-3%), regardless of plan type, and most health plans limit evaluations to
      assessment of member satisfaction and utilization. Only 35%-45% of HMOs, and no
      PPO/indemnity plans, assess the impact of health-promotion programs on health
      risks and behaviors, health status, or health care costs. CONCLUSION: For the
      majority of California's PPO and indemnity plans, health promotion is not an
      integral part of their business. For the majority of HMOs, health-promotion
      programs are offered primarily as a marketing vehicle. However, a substantial
      minority of HMOs offer health-promotion programs to achieve other organizational
      goals of health improvement and cost control.

PMID- 9569216
TI  - Prevention of adenoviral acute respiratory disease in Army recruits: cost
      effectiveness of a military vaccination policy.
AB  - INTRODUCTION: Since 1971 widespread vaccination has limited the number of
      adenoviral acute respiratory disease (ARD) outbreaks in Army recruits. Increased
      vaccine costs have recently threatened the continuation of the vaccination
      program. METHODS: We conducted a cost-effectiveness analysis to assess the
      consequences of changing the year-round Army adenovirus vaccination program to
      (1) seasonally targeted vaccine administration (only during the high-risk period)
      or (2) complete discontinuation of the program from the perspective of total cost
      to the Army. Costs included vaccination costs and direct and indirect medical and
      military training costs. Health outcomes were estimated as the number of
      hospitalizations for ARD prevented. In the reference case, the incidence rate
      among unvaccinated and vaccinated individuals was 4.06 and 1.5 per 100 person
      weeks, respectively. Results are expressed for a cohort of 76,171 recruits.
      RESULTS: In the absence of adenoviral vaccination, a projected 12,370 cases of
      ARD hospitalization would occur, costing $26.4 million annually. A seasonally
      targeted program would prevent 7,800 cases of ARD and save $16.1 million over no
      vaccination. Year-round immunization would not prevent any additional cases but
      would save $15.5 million over no vaccination. Year-round vaccination would become
      the cost-effective strategy if ARD incidence during the low-risk months were to
      increase. CONCLUSION: Vaccination of Army recruits by any schedule was cost
      saving due to the high level of prevented disease and averted hospitalizations.
      Even though a seasonally targeted program provided the greatest cost-savings,
      year-round vaccination must remain an option due to the potential for adenoviral
      ARD outbreaks in the low-risk period.

PMID- 9569217
TI  - Sarcoidosis diagnoses among U.S. military personnel: trends and ship assignment
      associations.
AB  - BACKGROUND: Sarcoidosis is a granulomatous disorder of unknown cause that usually
      first involves the lungs. After the diagnosis of a deck grinder was changed from
      sarcoidosis to dust-induced lung disease by the VA, the Navy asked the National
      Institute for Occupational Safety and Health (NIOSH) to determine if Navy work
      environments have been associated with lung diseases, some of which may have been
      reported as "sarcoidosis." METHODS: Sarcoidosis-related associations were
      measured using a case-control approach involving the modern personnel database of
      the Naval Health Research Center (NHRC). Sarcoidosis incidence rates were also
      computed using total Navy manpower data, and previously published military data
      from the 1940s and 1950s were juxtaposed with current findings to gain a broader
      historical perspective. RESULTS: When reported sarcoidosis incidence rates from
      1943 to 1993 are examined, an unexplained peak of military sarcoidosis rates
      appears in the 1960s and 1970s along with a decline in the black/white ratio of
      these rates from about 17:1 to 6:1. The case-control analyses reveal a decreased
      risk for sarcoidosis diagnoses among men who worked only on "clean ships."
      CONCLUSIONS: These findings suggest that sarcoidosis-like diseases in the
      military may be associated with environmental factors. To implement effective
      primary prevention, early detection, and treatment programs for sarcoidosis-like
      disease, these trends and work environment patterns need to be explained.
      Clinical studies of Vietnam-War-era veterans, which assess their work exposures
      and job activities in more detail, may identify preventable causes among this
      generation, which has a historically high rate of disease.

PMID- 9569218
TI  - A survey of physicians who studied public health during medical school.
AB  - INTRODUCTION: The need for more physicians trained in prevention, research
      methods, and management has been argued by many leaders in medical education.
      Columbia University attempts to address this need by providing medical students
      with a variety of options for studying public health. METHODS: A survey of
      Columbia's medical graduates who had taken elective courses in public health
      explored the reasons they began their studies, why some did not continue, their
      assessment of the value of public health courses, and their careers after
      graduation. RESULTS: Responses were received from 60 graduates. Health policy,
      international health, and clinical prevention were the primary interests leading
      them to study public health. Courses in epidemiology, biostatistics, and policy
      and management were cited as most useful. The pressure of clinical training was
      the major reason why some did not complete the master of public health (MPH)
      degree in a timely fashion. Among students who had enrolled in the MPH program
      and finished medical school before 1990, 84% eventually received the MPH,
      although some took as many as 12 additional years to complete the degree. Medical
      students who studied public health did not differ greatly from their classmates
      in their specialty choices, but those who completed the MPH chose academic,
      governmental, and corporate practice settings more frequently than other young
      physicians, and devoted more time to non-clinical activities. CONCLUSION: Public
      health educators can serve a variety of career needs for future physicians. In
      addition to personal interests, the presence of role models is an important
      reason students begin studying public health.

PMID- 9569219
TI  - Misleading nutrition claims on cracker packages prior to and following
      implementation of the Nutrition Labeling and Education Act of 1990.
AB  - OBJECTIVES: This study compared patterns in selected health claims on snack
      cracker packaging and fat content prior to and following enforcement of the
      Nutrition Labeling and Education Act of 1990 (NLEA). METHODS: Through
      observations at supermarkets in 1991 and 1995, the prevalence on packages of
      health claims that consumers associate with heart disease prevention was
      evaluated. The fat content of each product also was recorded. Criteria for
      potentially misleading claims were developed. RESULTS: Analysis of both cross
      sectional data and products that were available in both years showed that fat
      content, as well as the number of products containing target claims, had
      significantly decreased by 1995. The prevalence of potentially misleading claims
      also declined significantly, from 77% in 1991 to 49% in 1995. CONCLUSIONS:
      Although the data regarding the changes from 1991 to 1995 are encouraging, the
      prevalence of potentially misleading health claims for this food category
      continues to be high.

PMID- 9569220
TI  - The quality of Pap test specimens collected by nurses in a breast and cervical
      cancer screening clinic.
AB  - BACKGROUND: It is possible that nurses can help close the gap between the Healthy
      People 2000 clinical preventive services goals and current cancer screening rates
      by collecting Pap test specimens in clinical practices. The purpose of this
      analysis was to determine whether nurses can collect high-quality Pap tests.
      DESIGN: Retrospective cohort analysis of all Pap tests submitted to a commercial
      pathology laboratory between January 1, 1996 and July 31, 1996. Pap tests
      collected by the nurses at Rosebud Hospital (N = 404) were compared to the Pap
      tests collected by other providers at the Rosebud Hospital (N = 118) and the Pap
      tests collected by providers from all other sites (N = 22,696). SETTING: The
      Indian Health Service Hospital, Rosebud, South Dakota. SUBJECTS: Eight nurses who
      had been trained to collect Pap test specimens. MAIN OUTCOME MEASURES: The
      proportion of Pap test specimens that were wholly satisfactory and the proportion
      of Pap test specimens collected from nonpregnant patients that lacked
      endocervical cells. RESULTS: The proportion of specimens that were wholly
      satisfactory was 79.8% (95% CI = 75.9-83.7) for the nurses, 65.3% (95% CI = 56.7
      73.9) for other Rosebud providers, and 81.7% (95% CI = 81.2-82.2) for non-Rosebud
      providers. The proportion of specimens that lacked endocervical cells and were
      from nonpregnant patients was 6.4% (95% CI = 4.0-8.8) for Rosebud nurses, 8.5%
      for other Rosebud providers (95% CI = 3.5-13.5), and 7.9% for non-Rosebud
      providers (95% CI = 7.6-8.2). CONCLUSIONS: After one week of training, nurses can
      collect Pap test specimens that are of the same quality as the specimens
      collected by physicians, nurse practitioners, and physician assistants. The
      widespread availability of female nurses and the high quality of their work
      suggest that they can contribute to the Healthy People 2000 goals by collecting
      Pap test specimens.

PMID- 9569221
TI  - Accuracy of self-report of mammography and Pap smear in a low-income urban
      population.
AB  - BACKGROUND: Cancer screening history can often be obtained only by self-report,
      particularly for disadvantaged populations. We examined the accuracy of self
      report of mammography and Pap smear for an urban, low-income population. METHODS:
      Women attending non-primary care clinics (mostly surgery and orthopedics) at a
      large public teaching hospital in Minneapolis between July 1992 and May 1993 were
      queried about their screening history (n = 477). The women were interviewed by a
      trained peer-recruiter and asked whether they had ever heard of a Pap smear or
      mammogram, whether they had ever had one, where it was done, and when the last
      one was. We verified self-report by checking medical records where the test was
      performed. RESULTS: The positive and negative predictive value of recall of
      mammography in the previous year was 72.4% and 90.6%, respectively. The figures
      for Pap smear recall were somewhat lower, 65.5% and 85.9%, respectively. We found
      a record of a mammogram in 88% of women able to recall the year. Of these,
      slightly over two-thirds recalled their mammogram in the same year as their
      record indicated. Inaccurate recalls were more commonly of the "telescoping"
      type, i.e., tests were recalled as having occurred more recently than was the
      case. Recall was substantially better for recent tests. Results for Pap smear
      recalls were broadly similar. CONCLUSIONS: The accuracy of self-report of
      mammography and Pap smear is relatively poor for medical practice but is
      acceptable in population surveys with appropriate correction for overreporting.

PMID- 9569222
TI  - Ability to measure sensitive adolescent behaviors via telephone.
AB  - INTRODUCTION: Difficulty in measuring sensitive behaviors in 12-15-year-old
      adolescents is a barrier to research. This study determined whether early
      adolescents reported substance use and sexual activity similarly in assisted
      paper-and-pencil versus touch-tone telephone responses. METHODS: Adolescents 12
      15 years old completed confidential, interviewer-assisted questionnaires first in
      a physician office by paper-and-pencil and then at home by touch-tone
      approximately 3 months later. Adolescents were from a high-risk urban area, 71%
      were minority, and all had parent consent to participate. RESULTS: The follow-up
      participation rate was 94% (follow-up n = 207). Test-retest stability was
      generally poor for low-frequency behaviors such as injection drug use, anal
      intercourse, and sexual behaviors in 12-13-year-olds. Test-retest stability was
      fair to good for common substance use items. Test-retest stability was generally
      good among females and 14-15-year-old adolescents, and poor to fair among males
      and 12-13-year-olds, for common sexual experiences in the last 3 months. Test
      retest stability was generally good to excellent for all lifetime sexual
      experiences except among 12-13-year-olds in which it was generally poor. Internal
      consistency of the self-esteem scale was high using both response technologies.
      Both response technologies reproduced correlations between substance use and
      lifetime sexual experience. CONCLUSION: A high participation rate and reliable
      data capture were achieved when assessing sensitive behaviors of 14-15-year-olds
      using touch-tone telephone response. Sexual behaviors were more reliably captured
      using a "lifetime" versus "last 3-month" reference period. Low prevalence
      contributed to poor reliability in 12-13-year-olds.

PMID- 9569224
TI  - Strategies for reaching Asian Americans with health information.
AB  - INTRODUCTION: Cultural, linguistic, and economic barriers place many Asian
      Americans in jeopardy of missing opportunities for disease prevention, early
      diagnosis, prompt treatment, and participation in clinical trials. One way to
      learn how to address these barriers is through the development of a demonstration
      health education and prevention program focused on an indicator disease such as
      cancer. METHODS: In 1994, the University of California, San Diego (UCSD) Cancer
      Center began a highly focused cancer education program. Staffing was done with a
      variety of bicultural and bilingual undergraduates recruited from local colleges
      and trained to work as community health educators. Asian grocery stores were
      selected as optimal educational sites. Adaptation of sheltered English teaching
      techniques and hands-on teaching aids helped to overcome language and educational
      barriers. The educational intervention was evaluated using unobtrusive measures.
      RESULTS: With the volunteers' help, culturally sensitive means to disseminate
      information on cancer were evaluated. A variety of approaches evolved that
      effectively bridged many communication barriers. Fear of cancer itself, belief
      that thinking about cancer could provoke the onset of the disease, and financial
      barriers to care proved to be just as formidable barriers to cancer education in
      this ethnic group as they are in others. Using student volunteers and donated
      store space, this educational program was conducted with minimal expense.
      CONCLUSION: Reaching this population with the help of ethnically and
      linguistically compatible students was effective, but the barriers they faced
      when trying to connect with their potential audience were still considerable.
      Rigorous evaluation of the strategies used in this intervention is warranted.

PMID- 9569223
TI  - Tobacco advertisements: one of the strongest risk factors for smoking in Hong
      Kong students.
AB  - STUDY OBJECTIVE: To describe the prevalence of smoking in junior secondary school
      students in Hong Kong and to analyse the relationship between a range of risk
      factors and ever-smoking experience, including tobacco advertisements. METHODS:
      Cross-sectional survey using an anonymous standardised self-administered
      questionnaire. SETTING: 61 randomly selected secondary schools in Hong Kong.
      PARTICIPANTS: 6,304 form 1 to 3 Chinese students from 172 classes (51% girls and
      49% boys; 90% were aged 12 to 15 years). RESULTS: The smoking status (95%
      confidence interval) was: (1) never smoker, 71.1% (70.0%-72.2%), (2) tried only,
      15.5% (14.6%-16.4%), (3) used to smoke but not now, 4.2% (3.7%-4.7%), (4) smoked
      < 1 cigarette per week, 2.9% (2.5%-3.4%), (5) smoked 1-6 per week, 1.7% (1.4%
      2.0%), and (6) smoked > 6 per week, 4.5% (4.0%-5.0%). In a backward stepwise
      logistic regression model, ever-smoking (including categories 2 to 6 above) was
      independently associated with thirteen factors, including gender (boys),
      increasing age, place of birth (outside Hong Kong, mainly China), poor knowledge
      of the hazards of smoking, positive attitudes to smoking, smoking in family
      members, participation in tobacco promotional activities, and perception of
      cigarette advertisements as attractive. Among the strongest associations observed
      was the youth's perception of cigarette advertisements as attractive, with the
      adjusted odds ratio (95% confidence interval) of 2.68 (2.33-3.07). CONCLUSIONS:
      Smoking among young people is an important public health problem. Although the
      causes are multifactorial, in Hong Kong environmental tobacco advertising is an
      important risk factor that can be removed by banning all forms of tobacco
      promotion to young people.

PMID- 9569225
TI  - Defining competencies and performance indicators for physicians in medical
      management.
AB  - The recent and profound changes in the American health care delivery system have
      created a need for physicians who are trained and willing to assume a high level
      of responsibility for managing evolving health care organizations. Yet most
      physicians receive no formal training in medical administration and management
      because changes in medical school and residency education have lagged behind
      changes in clinical practice and reimbursement. To avoid haphazard approaches and
      unnecessary duplication of resources, it is important for physicians involved in
      managerial medicine to collectively identify competencies in this area needed in
      the marketplace. The American College of Preventive Medicine (ACPM), with funding
      from the Health Resources and Services Administration (HRSA), undertook an effort
      to identify competencies essential for physicians who will fill leadership roles
      in medical management. Like ACPM's earlier effort to develop core competencies in
      preventive medicine, this project drew upon the theoretical model of competency
      based education. This article describes the strategy we followed in reaching
      consensus among a diverse group of physician executives and preventive medicine
      residency program directors, and includes the list of medical management
      competencies and performance indicators developed. Recurrent issues that can
      sidetrack competency development projects are also presented as well as
      suggestions for overcoming them. The competencies can serve as a framework for
      expanding current core preventive medicine training in management and
      administration and for developing new training programs to equip physicians with
      the special expertise they will need to provide management leadership within the
      changing landscape of health care delivery.

PMID- 9569226
TI  - Vaccine risk communication.

PMID- 9569227
TI  - Managed care and public health.

PMID- 9569228
TI  - Synaptic mechanisms in auditory cortex function.
AB  - Neurons in the auditory cortex (AC) respond to acoustic stimuli in diverse ways.
      Short latency responses code for the physical properties of stimuli, i.e., their
      frequency and intensity, whereas longer latency potentials may code for
      behavioral significance or other features. Despite a huge number of studies that,
      over the years, have reported on acoustic-evoked short and long-latency
      potentials, remarkably little is understood regarding the cellular mechanisms
      underlying these responses. Such information is critical to a full understanding
      of auditory information processing. This review summarizes the available data on
      synaptic and cellular mechanisms in AC neurons that have been obtained using
      electrophysiological methods with in vivo and in vitro preparations. It is
      apparent that the fundamental mechanisms identified in recent studies can be used
      in the near future to develop an integrated understanding of the cellular bases
      of information processing in auditory cortex.

PMID- 9569229
TI  - Transfer of the human Alpha1-antitrypsin gene into pulmonary macrophages in vivo.
AB  - Several viral and nonviral methods have introduced functional genes into the
      lungs. An alternative strategy, receptor-mediated gene transfer, exploits the
      ability of receptors on the surface of cells to bind and internalize DNA
      complexes and could potentially be used to deliver genes to specific cells in the
      lung. The gene encoding human alpha1-antitrypsin (A1AT) was delivered to
      macrophages in vitro and in vivo by targeting the mannose receptor with mannose
      terminal molecular conjugates. The human A1AT transcript was detected 2 d after
      transfection of macrophages in culture, but transgene expression was transient.
      Human A1AT protein was secreted into the culture medium, and Western blot
      hybridization revealed the mature human antiprotease. In addition, Sprague-Dawley
      rats underwent intravenous injections of increasing doses of plasmid DNA (0.2 mg,
      1.0 mg, and 2.0 mg) complexed to the molecular conjugate. Four days after
      transfection, human A1AT mRNA was found in lungs from six of the 13 rats (46%)
      that received the higher doses of plasmid. Transgene expression was limited to
      cells in perivascular and alveolar regions, which conformed to the distribution
      of pulmonary macrophages. Human A1AT was measured in the epithelial lining fluid
      of rats treated with transfection complexes. Animals that received 1.0 mg of
      plasmid had human A1AT levels of 7.4 +/- 3.4 pM, which was significantly
      different from nontransfected and mock-transfected controls. Thus the mannose
      receptor permitted direct delivery of genes to pulmonary macrophages, though
      transgene expression was detected in the lung only at low levels.

PMID- 9569230
TI  - Mechanical stimulation initiates intercellular Ca2+ signaling in intact tracheal
      epithelium maintained under normal gravity and simulated microgravity.
AB  - We investigated mechanically induced cell-to-cell Ca2+ signaling in a preparation
      of rabbit tracheal epithelium close to its in vivo condition. We used confocal
      microscopy to analyze changes in intracellular free calcium concentration
      ([Ca2+]i) in intact ciliated tracheal mucosal explants loaded with the Ca2+
      indicator dye, fluo-3. When a single cell in the epithelium was transiently
      stimulated with a microprobe, [Ca2+]i increased in the stimulated cell and then
      increased in surrounding cells. In the absence of extracellular Ca2+, the [Ca2+]i
      increases had a smaller amplitude and spread to fewer cells. Treatment of the
      cells with thapsigargin, in the presence of extracellular Ca2+, more markedly
      reduced the spread of elevated [Ca2+]i. These results suggest that the propagated
      [Ca2+]i increases are due to mobilization of Ca2+ from intracellular stores and,
      possibly, the influx of extracellular Ca2+. The mechanically stimulated [Ca2+]i
      increases were accompanied by propagated increases in ciliary beat frequency.
      Since microgravity has been shown to alter signal transduction, we investigated
      whether simulated microgravity affects the mechanically stimulated cell-to-cell
      Ca2+ signaling observed in tracheal epithelium. Tissues were maintained for 3-8 d
      in a rotating wall vessel which simulates microgravity conditions. Cells
      maintained in simulated microgravity exhibited mechanically induced [Ca2+]i
      increases not significantly different in magnitude, in speed of propagation, or
      in the number of cells involved, from tissue maintained at unit gravity. Our
      results suggest that intercellular Ca2+ signaling coordinates cellular activity,
      including ciliary beating, within the tracheal epithelium in vivo and that this
      function is not compromised in microgravity.

PMID- 9569231
TI  - Increased endothelin-1 and its localization during the development of bleomycin
      induced pulmonary fibrosis in rats.
AB  - Endothelin-1 (Et-1) has been implicated in the pathogenesis of pulmonary fibrosis
      with increased levels in the lung tissue of patients with pulmonary fibrosis and
      profibrotic effects in vitro. In this study we have investigated the temporal
      changes in lung Et-1 levels and immunohistochemical localization in relation to
      collagen deposition during the development of bleomycin-induced pulmonary
      fibrosis in rats. Lung Et-1 content doubled by 3 d following the intratracheal
      instillation of bleomycin, and continued to increase up to 7 d when values were
      about threefold greater than controls. Thereafter, the values for bleomycin
      treated animals remained constant up to 21 d. There was no change in collagen
      content at 3 d but after 7 d there was a 25% increase and by 21 d levels were
      almost double those of the controls. In normal lung, Et-1 was predominantly
      associated with epithelial cells of conducting and nonconducting airways.
      Following bleomycin administration, intense staining of macrophages and
      conducting airway and alveolar epithelial cells was observed with marked staining
      of perivascular, peribronchiolar, and alveolar septal connective tissue, as well
      as the venular and arterial intima and media. These results demonstrate elevation
      of Et-1 levels prior to an increase in collagen content which, along with its
      localization within developing fibrotic lesions, provides further evidence of a
      profibrotic role for Et-1 in the pathogenesis of pulmonary fibrosis.

PMID- 9569232
TI  - Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion
      molecule-1 expression in human lung microvascular endothelial cells.
AB  - Recent studies suggest that increased vascular cell adhesion molecule-1 (VCAM-1)
      expression on vascular endothelium in bronchial mucosa biopsies correlates with
      interleukin-4 (IL-4) levels in bronchiolar lavage fluid of allergic asthmatics.
      The severity of asthma in patients allergic to house dust mite has also been
      shown to correlate with lipopolysaccharide (LPS), rather than allergen,
      concentration in dust. We hypothesized that to induce effective VCAM-1 expression
      in human lung microvascular endothelial cells (HLMVEC), IL-4 may require the
      presence of a co-stimulus such as LPS. To test this hypothesis we measured, by
      enzyme-linked immunosorbent assay, induction of cell adhesion molecule expression
      on, and human eosinophil adhesion to, cultured HLMVEC monolayers pretreated with
      IL-4 alone or combined with LPS. IL-4 synergized with LPS to induce VCAM-1
      expression at 24, 48, or 72 h, whereas IL-4 alone induced expression at 72 h
      only. IL-4 did not induce expression of intercellular adhesion molecule-1 or E
      selectin or alter LPS-induced expression of either. Pre-exposure of HLMVEC to LPS
      or IL-4 (1 h), followed by IL-4 or LPS, respectively (23 h), also induced VCAM-1
      expression. Eosinophil adhesion to HLMVEC monolayers treated with IL-4 and LPS
      together, but not alone, significantly (P < 0.001) increased from 9.6 +/- 1.5%
      (control) to 26.9 +/- 3.3% and was inhibited by a monoclonal antibody against the
      VCAM-1 ligand, very late antigen-4. Analysis of VCAM-1 mRNA revealed synergism
      between IL-4 and LPS which may, in part, contribute to enhanced VCAM-1
      expression. These results suggest that the presence of a co-stimulus such as LPS
      may be necessary for IL-4 to effectively induce VCAM-1 expression in lung
      microvasculature.

PMID- 9569233
TI  - Interleukin-5 mRNA stability in human T cells is regulated differently than
      interleukin-2, interleukin-3, interleukin-4, granulocyte/macrophage colony
      stimulating factor, and interferon-gamma.
AB  - Interleukin-5 (IL-5) transcriptional activation and mRNA stability were
      investigated in a human TH0 T-cell clone (SP-B21) and in nonclonal CD4 TH2 cells,
      differentiated in vitro from peripheral blood T cells. Cells were stimulated with
      alpha-CD3 monoclonal antibody (mAb) with and without alpha-CD28 mAb. Comparison
      to other cytokine genes revealed aspects of mRNA regulation unique to IL-5. The
      half-life (t1/2) of IL-5 mRNA, determined by addition of actinomycin D (ActinoD)
      or cyclosporin A (CSA) was longer (by >= 2 h) than that of IL-2, IL-3, IL-4,
      interferon-gamma, or granulocyte/macrophage colony-stimulating factor. With the
      exception of IL-5, t1/2 values were significantly shorter with CSA as the
      transcriptional inhibitor than with ActinoD. The t1/2 value of IL-5 mRNA, but not
      the other cytokine transcripts, determined with either ActinoD or CSA, was longer
      than predicted from the kinetics of steady-state mRNA decline. Co-stimulation of
      both cell types with alpha-CD28 mAb increased the stability of cytokine
      transcripts weakly, and IL-5 remained the most stable transcript. Thus, the
      degradation pathway that targets IL-5 is distinct from the other cytokine
      transcripts measured and involves proteins whose transcription is blocked by
      ActinoD and CSA. From examination of the levels of transcription initiation
      (nuclear run-on assay) and steady-state mRNA attained in cultures stimulated in
      the presence of the protein synthesis inhibitor, cycloheximide, only IL-5
      transcription initiation had an absolute dependency on new protein synthesis.

PMID- 9569234
TI  - Quantitative analysis of mRNA encoding MUC1, MUC2, and MUC5AC genes: a
      correlation between specific mucin gene expression and sialomucin expression in
      non-small cell lung cancer.
AB  - The expression of mucins is important for tumor invasiveness and metastasis. In
      our previous report (Am. J. Respir. Crit. Care Med. 1997; 155:1419-1427), non
      small cell lung cancers bearing sialomucin expression tended to relapse earlier
      than those without sialomucin. However, it remained unclear whether the
      expression of sialomucin in lung cancer is caused by an abnormal glycosylation
      process or by the expression of a specific mucin gene product. To address this
      problem, we established a modified quantitative competitive polymerase chain
      reaction (QC-PCR) analysis. RNA internal standards of MUC1, MUC2, and MUC5AC non
      tandem repeat sequences were constructed, and known copy numbers of mucin RNA
      internal standards were introduced into reverse transcription-polymerase chain
      reactions (RT-PCR) for each mucin gene in order to compete with native mucin gene
      RNA during the reaction. The RNA of Gbeta-like gene (a housekeeping gene) was
      used as internal control for the RNA analysis. Twenty-five lung cancer tissues
      (13 adenocarcinomas and 12 squamous cell carcinomas) were used for analysis. Mann
      Whitney rank sum test was applied to compare the expression amounts of different
      mucin genes in tissues. The results revealed that adenocarcinoma expressed higher
      amounts of MUC5AC gene than did squamous cell carcinoma (P = 0.03). The
      expression amount of MUC5AC correlated positively with the expression status of
      sialomucin (P = 0.012). Further studies are anticipated to elucidate the
      underlying mechanism contributing to this phenomenon.

PMID- 9569235
TI  - ATP-independent membrane depolarization with ischemia in the oxygen-ventilated
      isolated rat lung.
AB  - We hypothesize that lung ischemic injury is related to cessation of flow leading
      to endothelial cell membrane depolarization and activation of oxidant-generating
      systems. Cell membrane potential was assessed in isolated, oxygen ventilated,
      Krebs-Ringer bicarbonate buffer-dextran-perfused rat lungs by lung surface
      fluorescence after infusion of bis-oxonol or 5,5',6,6'-tetrachloro-1, 1',3,3'
      tetraethylbenzimidazolyl-carbocyanine iodide (JC-1), voltage-sensitive dyes.
      Surface fluorometry showed increased bis-oxonol fluorescence (34.7 +/- 3.3% above
      baseline) and decreased JC-1 fluorescence (24.5 +/- 4.5% below baseline) with
      ischemia, compatible with membrane depolarization. Fluorescence change was
      initiated within 1-2 min of the onset of ischemia and was rapidly reversible with
      reperfusion. Fluorescence changes varied with perfusion flow rate; maximal
      increase occurred with the transition from 1.8 ml/min to zero flow. Elevation of
      static intravascular pressure resulted in only a minor increase of bis-oxonol
      fluorescence. In situ subpleural fluorescence microscopy showed that endothelial
      cells are the major site of the increased bis-oxonol fluorescence signal with
      ischemia. These results indicate that endothelial cell membrane depolarization
      represents an early event with lung ischemia. Since the adenosine triphosphate
      content of lung was unchanged with ischemia in the O2-ventilated lungs, we
      postulate that membrane depolarization results from elimination of shear stress,
      possibly via inactivation of flow-sensitive K+-channels.

PMID- 9569236
TI  - Changes in expression of 15-lipoxygenase and prostaglandin-H synthase during
      differentiation of human tracheobronchial epithelial cells.
AB  - The purpose of our studies was to examine differentiation-dependent expression of
      15-lipoxygenase (15-LO) and prostaglandin H synthase (PGHS) isoforms in cultured
      normal human tracheobronchial epithelial cells. In the presence of retinoic acid
      (RA) the cultures differentiated into a mucociliary epithelium. When cultured in
      RA-depleted media, the cultures differentiated into a squamous epithelium. In the
      absence of RA the cultures did not express 15-LO or either of the PGHS isoforms.
      The PGHS-1 isoform was not expressed in RA-sufficient cultures, but both PGHS-2
      messenger RNA (mRNA) and protein were strongly expressed, and prostaglandin E2
      (PGE2) was produced during the predifferentiation phase. No PGHS-2 expression or
      PGE2 could be detected in fully differentiated mucociliary cultures. 15-LO showed
      the opposite expression pattern: neither mRNA nor protein were detected during
      the predifferentiation stage, but both were strongly expressed once mucous
      differentiation had occurred. Cytosolic phospholipase A2 protein was expressed
      throughout all stages of growth and differentiation. The cultures generated no 15
      LO metabolites when incubated with 10 microM to 50 microM arachidonic acid (AA)
      and stimulated with ionophore. However, lysates prepared from such cultures
      generated 15-hydroxyeicosatetraenoic acid (15-HETE) and 12-HETE from AA,
      indicating that the cells contained active enzyme. When cultures expressing 15-LO
      protein were incubated with 10 microM linoleic acid (LA) instead of AA, and were
      stimulated with ionophore, they generated 13-hydroxy-9,11-octadecadienoic acid.
      LA rather than AA appeared to be the preferred substrate for the 15-LO enzyme.
      Our studies indicated that the expression of 15-LO and PGHS-2 is differentiation
      dependent in airway epithelial cells.

PMID- 9569237
TI  - Lung polymers in Z alpha1-antitrypsin deficiency-related emphysema.
AB  - Patients with alpha1-antitrypsin (alpha1-AT) deficiency are at risk of developing
      early-onset panlobular basal emphysema, which has been attributed to uncontrolled
      proteolytic activity within the lung. Severe genetic deficiency of alpha1-AT is
      most commonly due to the Z mutation (342Glu--> Lys), which results in a block in
      alpha1-AT processing within the endoplasmic reticulum of hepatocytes. The
      retained alpha1-AT forms inclusions, which are associated with neonatal
      hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. Our recent studies
      have shown that the accumulation of alpha1-AT is due to the Z mutation perturbing
      the structure of alpha1-AT to allow polymer formation, with a unique linkage
      between the reactive center loop of one alpha1-AT molecule and the A beta-pleated
      sheet of a second. The detection of loop-sheet polymers and other conformations
      of alpha1-AT in the lungs of patients with emphysema has been technically
      difficult. We show here that transverse urea-gradient-gel (TUG) electrophoresis
      and Western blot analysis may be used to characterize conformations of alpha1-AT
      in dilute samples of bronchoalveolar lavage fluid (BALF). This technique was used
      to demonstrate loop-sheet polymers in the lungs of patients with Z alpha1-AT
      deficiency-related emphysema. Polymers were the predominant conformational form
      of alpha1-AT in BALF from the lungs of two of five Z homozygotes with emphysema,
      but were not detectable in any of 13 MM, MS, or MZ alpha1-AT controls. Because
      alpha1-AT loop-sheet polymers are inactive as proteinase inhibitors, this novel
      conformational transition will further reduce the levels of functional proteinase
      inhibitor in the lungs of the Z alpha1-AT homozygote, and so exacerbate tissue
      damage.

PMID- 9569238
TI  - Ligation of the beta2 integrin triggers activation and degranulation of human
      eosinophils.
AB  - Evidence suggests that cellular adhesion is critical for eosinophil effector
      functions. Here, we tested the hypothesis that an adhesion molecule, specifically
      beta2 integrin, participates in intracellular signaling events of eosinophils.
      Eosinophils stimulated with interleukin (IL)-5 and adherent to protein-coated
      tissue culture plates via beta2 integrin (CD18) showed tyrosine phosphorylation
      of a number of proteins. Among these proteins, tyrosine phosphorylation of the
      105 kD and 115 kD proteins and the product of the c-cbl protooncogene, Cbl, was
      specifically inhibited using soluble anti-CD18 monoclonal antibody (mAb) to block
      eosinophil cell adhesion. Furthermore, phosphoinositide turnover of IL-5
      stimulated adherent eosinophils was also inhibited by anti-CD18 mAb, suggesting
      that cellular adhesion plays important roles in eosinophil signal transduction.
      alphaM beta2 (Mac-1, CD11b/18) was one of the beta2 integrins involved in
      eosinophil adhesion to protein-coated plates. We found that direct ligation of
      eosinophil alphaM beta2 with anti-CD11b mAb coupled to polystyrene microbeads
      induced tyrosine phosphorylation of a 115 kD protein and Cbl. Furthermore, anti
      CD11b mAb microbeads induced increases in both phosphoinositide hydrolysis and
      the eosinophil degranulation response. Control antibodies, such as mouse myeloma
      IgG1 and anti-HLA class I antigen mAb, did not induce these cellular responses.
      These results suggest that engagement of beta2 integrin either by cell adhesion
      or by anti-CD11b mAb triggers activation of an intracellular signaling cascade,
      including protein tyrosine phosphorylation and phosphoinositide turnover, and
      subsequent cellular degranulation in human eosinophils. Tyrosine phosphorylation
      of a 115 kD protein and Cbl may play important roles in adhesion-dependent
      cellular functions of eosinophils.

PMID- 9569239
TI  - Retention and intracellular distribution of instilled iron oxide particles in
      human alveolar macrophages.
AB  - Bronchoalveolar lavage (BAL) was used to sample retention of particles within the
      alveolar macrophage (AM) compartment at various times from 1 to 91 d following
      intrapulmonary instillation of 2. 6-microm-diameter iron oxide (Fe2O3) particles
      in human subjects. Particles were cleared from the lavagable AM compartment in a
      biphasic pattern, with a rapid-phase clearance half-time of 0.5 d and long-term
      clearance half-time of 110 d, comparable to retention kinetics determined by more
      traditional methods. The intracellular distribution of particles within lavaged
      AMs was similar in bronchial and alveolar BAL fractions. AMs with high
      intracellular particle burdens disappeared from the lavagable phagocytic AM
      population disproportionately more rapidly (shorter clearance half-time) than did
      AMs with lower particle burdens, consistent with the occurrence of a particle
      redistribution phenomenon as previously described in similar studies in rats. The
      rates of AM disappearance from the various particle burden categories was
      generally slightly slower in bronchial fractions than in alveolar fractions. The
      instillation of particles induced a transient acute inflammatory response at 24 h
      postinstillation (PI), characterized by increased numbers of neutrophils and
      alveolar macrophages in BAL fluids. This response was subclinical and was
      resolved within 4 d PI.

PMID- 9569240
TI  - Cytokine mediation of ozone-induced pulmonary adaptation.
AB  - Previous studies have shown that a single exposure of animals to ozone (O3) can
      induce protection or adaptation to the acute injurious effects of a subsequent O3
      challenge. Although a number of mechanisms have been proposed to account for this
      response, none appear to be fully explanatory. We examined the role interleukin
      (IL)-6 may play in the induction of adaptation to O3-induced pulmonary injury. A
      statistically significant 29-fold increase in bronchoalveolar lavage fluid IL-6
      levels was observed in rats exposed to 0.5 ppm O3 during nighttime hours when
      compared with daytime hours even though similar kinetics of inflammation were
      induced by each exposure. Animals receiving an initial nighttime O3 exposure
      showed a lesser degree of inflammation following a subsequent O3 exposure when
      compared with animals which received an initial daytime exposure. Rats pretreated
      with IL-6 both intratracheally and intraperitoneally and subsequently exposed to
      O3 showed a lesser degree of cellular inflammation when compared with respective
      controls. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) prior to
      the nighttime O3 exposure completely abrogated the O3-induced cellular adaptive
      response without effecting the inflammatory response induced by the initial
      nighttime O3 exposure. In fact, administration of anti-IL-6ra augmented the
      neutrophil influx following the second O3 exposure. Anti-IL-6ra treatment did not
      alter the pulmonary edema adaptive response, suggesting that the O3-induced
      cellular and edema adaptive responses are regulated by different mechanisms. Our
      data indicate that mobilization of pulmonary antioxidants does not play a role in
      the IL-6-mediated early cellular adaptive response and suggest that IL-6 is an
      essential mediator of the O3-induced cellular adaptive response.

PMID- 9569241
TI  - Expression of IgE heavy chain transcripts in the sinus mucosa of atopic and
      nonatopic patients with chronic sinusitis.
AB  - We have recently shown the increased mRNA expression of interleukin (IL)-4 and IL
      13 in sinus biopsies from allergic subjects with chronic sinusitis (ACS), whereas
      only IL-13 mRNA was elevated in biopsies obtained from nonallergic subjects with
      chronic sinusitis (NCS). In the lymph nodes and spleen, these cytokines may
      promote IgE production through transcriptional activation of the germline IgE
      heavy chain promoter, an event which precedes immunoglobulin isotype switching to
      IgE in B cells. We hypothesized that local expression of IL-4 and/or IL-13 might
      act by inducing germline IgE heavy chain transcript expression locally in the
      sinus mucosa of chronic sinusitis patients. Mucosal sinus biopsies were obtained
      from 13 patients with ACS, 12 subjects with NCS, and 11 normal control
      individuals. The numbers of B cells in the sinus mucosa were studied by
      immunocytochemistry with anti-CD20 monoclonal antibodies. In situ hybridization
      was performed using antisense radiolabeled riboprobes complementary to the IgE
      epsilon -heavy chain germline (Iepsilon) and heavy chain constant region
      (Cepsilon) gene transcripts. Riboprobes specific for the IgG gamma-heavy chain
      constant region (Cgamma) were used as an isotype control. Immunocytochemical
      analysis indicated augmented numbers of CD20-positive B cells in the biopsies
      obtained from ACS patients compared with NCS subjects (P < 0.05) and normal
      control subjects (P < 0.01). Statistically significant increases were observed in
      the numbers of cells expressing Iepsilon and Cepsilon transcripts in the sinus
      mucosa of ACS patients compared with those with NCS (P < 0. 001) and normal
      controls (P < 0.001), while Cgamma RNA expression did not differ significantly
      between the groups. In three randomly selected ACS biopsies, 92-100% of cells
      expressing Cepsilon transcripts and 100% of Iepsilon RNA-positive cells
      coexpressed CD20 immunoreactivity. Cells expressing Cepsilon transcripts were
      also significantly increased in NCS compared with normal controls (P < 0. 05).
      The results of this study suggest that local IgE class switching occurs in the
      pathogenesis of ACS and that ACS and NCS are both associated with increased
      expression of Cepsilon transcripts.

PMID- 9569242
TI  - Adaptation of rat type II pneumocytes to NO2: effects of NO2 application mode on
      phosphatidylcholine metabolism.
AB  - Previous studies have shown that nitrogen dioxide (NO2) inhalation affects the
      extracellular surfactant as well as the structure and function of type II
      pneumocytes. Since in these studies there were great variabilities in oxidant
      concentration, duration of exposure, and mode of NO2 application, we evaluated
      the influence of the NO2 application mode on the phospholipid metabolism of type
      II pneumocytes. Rats were exposed to identical NO2 body doses (720 ppm x h),
      which were applied continuously (10 ppm for 3 d), intermittently (10 ppm for 8 h
      per day, for 9 d), and repeatedly (10 ppm for 3 d, 28 d rest, and then 10 ppm for
      3 d). Immediately after exposure, type II cells were isolated and evaluated for
      cell yield, vitality, phosphatidylcholine (PC) synthesis, and secretion. Type II
      pneumocyte cell yield from animals that had been continuously exposed to NO2 was
      significantly increased, whereas intermittently and repeatedly treated rats
      exhibited cell yields that were nonsignificantly enhanced. Vitality of the
      isolated type II pneumocytes was not affected by the NO2 exposure modes.
      Continuous application of 720 ppm x h NO2 resulted in increased activity of the
      cytidine-5-diphosphate (CDP)-choline pathway. After continuous NO2 application,
      specific activity of choline kinase, cytidine triphosphate (CTP):cholinephosphate
      cytidylyltransferase, uptake of choline, and pool sizes of CDP-choline and PC
      were significantly increased over those of controls. Intermittent application of
      this NO2 body dose also provoked an increase in PC synthesis, but this increase
      was less prominent than after continuous exposure. After repeated exposure, the
      synthesis parameters were comparable to those for cells from control animals.
      Whereas PC synthesis in type II cells was obviously stimulated by NO2, the
      secretory activity of the cells was reduced. Continuous exposure reduced this
      activity most, whereas intermittent exposure nonsignificantly reduced this
      activity as compared with that of controls. The repeated application of NO2
      produced no differences. We conclude that type II pneumocytes adapt to NO2
      atmospheres depending on the mode of its application, at least for the metabolism
      of PC and its secretion from isolated type II pneumocytes. Further studies are
      necessary to determine whether additional metabolic activities will also adapt to
      NO2 atmospheres, and if these observations are specific for NO2 or represent
      effects generally due to oxidants.

PMID- 9569244
TI  - Ion channels in renal glomerular mesangial cells.

PMID- 9569243
TI  - Histamine affects interleukin-4, interleukin-5, and interferon-gamma production
      by human T cell clones from the airways and blood.
AB  - High levels of histamine can be found in the airways of asthma patients. This
      study describes the effects of histamine on anti-CD3-induced production of IL-4,
      IL-5, and IFN-gamma by T cell clones from subjects with allergic asthma and
      healthy subjects. T cell clones were obtained from bronchoalveolar lavage (BAL)
      fluid and blood. The number of clones tested, and the percentage of clones in
      which histamine inhibited or enhanced cytokine production by more than 25%, were
      as follows: IL-4, 47, 8.5%, and 4.3%; IL-5, 43, 14%, and 30%; and IFN-gamma, 52,
      40%, and 15%. Inhibition of IL-5 and IFN-gamma production was reversed by IL-2.
      The enhancement of IFN-gamma production was associated with an enhancement of
      both IL-2 production and proliferation. In 21% of the clones a combined effect
      consisting of inhibition of IFN-gamma production and enhancement of IL-5
      production was found. This response was reversed by H2-receptor antagonists and
      was significantly associated with a histamine-induced increase in intracellular
      levels of cAMP. The role of cAMP in mediating the histamine effects was supported
      by the observations that the beta2-agonist salbutamol had effects similar to
      histamine and that high concentrations of PGE2 mimicked the inhibitory effects of
      histamine. Clones from BAL fluid and blood showed similar responses, as did
      clones from patients with asthma and from control subjects. The enhancement of
      IFN-gamma production by histamine, however, was found only in clones from healthy
      subjects. The results warrant further investigations on the role of cAMP in the
      regulation of cytokine production.

PMID- 9569245
TI  - Activation of the cardiac ryanodine receptor by sulfhydryl oxidation is modified
      by Mg2+ and ATP.
AB  - The reactive disulfide 4,4'-dithiodipyridine (4,4' DTDP) was added to single
      cardiac ryanodine receptors (RyRs) in lipid bilayers. The activity of native
      RyRs, with cytoplasmic (cis) [Ca2+] of 10(-7) M (in the absence of Mg2+ and ATP),
      increased within approximately 1 min of addition of 1 mM 4,4'-DTDP, and then
      irreversibly ceased 5 to 6 min after the addition. Channels, inhibited by either
      1 mM cis Mg2+ (10(-7) M cis Ca2+) or by 10 mM cis Mg2+ (10(-3) M cis Ca2+), or
      activated by 4 mM ATP (10(-7) M cis Ca2+), also responded to 1 mM cis 4,4'-DTDP
      with activation and then loss of activity. Po and mean open time (T(o)) of the
      maximally activated channels were lower in the presence of Mg2+ than in its
      absence, and the number of openings within the long time constant components of
      the open time distribution was reduced. In contrast to the reduced activation by
      1 mM 4,4'-DTDP in channels inhibited by Mg2+, and the previously reported
      enhanced activation by 4,4'-DTDP in channels activated by Ca2+ or caffeine (Eager
      et al., 1997), the activation produced by 1 mM cis 4,4'-DTDP was the same in the
      presence and absence of ATP. These results suggest that there is a physical
      interaction between the ATP binding domain of the cardiac RyR and the SH groups
      whose oxidation leads to channel activation.

PMID- 9569246
TI  - Evidence for two separate purinergic responses in Paramecium tetraurelia: XTP
      inhibits only the oscillatory responses to GTP.
AB  - The purine nucleotide GTP causes a complex behavioral response and two distinct
      electrophysiological responses in the ciliated protozoan Paramecium tetraurelia.
      One of the two electrophysiological responses is an oscillating current that is
      responsible for the repeated backward swimming episodes that constitute the
      behavioral response to GTP. The second electrophysiological response is a
      sustained current whose relationship to the first is unknown. Here we show that
      the purine nucleotides XTP can completely block both the behavioral response to
      GTP and its associated oscillating current, but not the sustained current induced
      by GTP. Notably, XTP alone causes a sustained current similar to that induced by
      GTP. We believe the data support the notion that P. tetraurelia possesses two
      distinct signal transduction pathways sensitive to purine nucleotides: one
      specific for GTP that leads to oscillating currents and behavior, and a second
      pathway activated by GTP and other purine nucleotides that leads to a sustained
      current.

PMID- 9569247
TI  - The impermeant ion methylammonium blocks K+ and NH4+ currents through KAT1
      channel differently: evidence for ion interaction in channel permeation.
AB  - The permeation properties of KAT1, an inward rectifying potassium channel from
      plant cells, were investigated with different ions in the external medium. With
      either K+, NH4+ or methylammonium (MA) in the external solution, the channel,
      expressed in Xenopus oocytes, appeared permeable to K+ and, to a lesser extent,
      to NH4+ but not to the slightly bigger, methylated analogue of NH4+, MA.
      Substituting NH4+ for K+ shifted the voltage dependency of channel activation
      further negative and hastened activation kinetics. This suggests that channel
      operation depends on the transported substrate. In mixed solution (50 mM K+, 50
      mM MA) MA inhibited K+ current in a voltage-independent manner. The maximum block
      did not exceed 50% of the K+ current. In contrast, when NH4+ was the permeant ion
      (50 mM NH4+, 50 mM MA) MA caused a voltage-dependent, slowly developing open
      channel block, achieving complete inhibition at very negative voltages. The
      latter block could be partially overcome by the addition of K+ in the external
      solution. The data support a model in which ions, after entering the channel
      pore, compete with different affinities for binding sites on their permeation
      pathway.

PMID- 9569248
TI  - Vestibular dark cells contain an H+/monocarboxylate- cotransporter in their
      apical and basolateral membrane.
AB  - The transport of lactate and pyruvate across membranes of vestibular dark cells
      (VDC) may be important under aerobic, ischemic or hypoxic conditions. This study
      addresses the questions whether VDC from the gerbil contain an H+/monocarboxylate
      cotransporter (MCT) and in which membrane, apical or basolateral, MCT is
      located. Uptake of monocarboxylates into VDC was monitored in functional studies
      by measuring the cytosolic pH (pHi) and by measuring the pH-sensitive equivalent
      short circuit current (Isc). Subtypes of the functionally identified MCT which
      are present in vestibular labyrinth tissues were identified as transcripts by
      cloning and sequencing of reverse-transcriptase polymerase chain reaction (RT
      PCR) products. Monocarboxylates but not dicarboxylates induced a transient
      acidification of pHi which was inhibited by 5 mM alpha-cyano-4-hydroxycinnamate
      (CHC) but not by 1 microM DIDS or 500 microM pCMBS. The initial rate of
      acidification induced by monocarboxylates was dose-dependent in the range between
      1 and 20 mM. K(m) values were for pyruvate 1.3, acetate 3.7, L-lactate 3.8 and D
      lactate 7.3 mM. Both apical and basolateral application of monocarboxylates
      caused a transient increase of Isc which was sensitive to 5 mM CHC. RT-PCR
      revealed the presence of transcripts for the MCT subtypes MCT1 and MCT2. The
      identity of transcripts was confirmed by sequence analysis. These observations
      suggest that VDC contain an MCT in their apical and basolateral membrane and that
      the vestibular labyrinth contains transcripts for the subtypes MCT1 and MCT2.

PMID- 9569249
TI  - Two distinct K+ channels in lamprey (Lampetra fluviatilis) erythrocyte membrane
      characterized by single channel patch clamp.
AB  - Two channels, distinguished by using single-channel patch-clamp, carry out
      potassium transport across the red cell membrane of lamprey erythrocytes. A small
      conductance, inwardly rectifying K(+)-selective channel was observed in both
      isotonic and hypotonic solutions (osmolarity decreased by 50%). The single
      channel conductance was 26 +/- 3 pS in isotonic (132 mM K+) solutions and 24 +/-
      2 pS in hypotonic (63 mM K+) solutions. No outward conductance was found for this
      channel, and the channel activity was completely inhibited by barium. Cell
      swelling activated another inwardly rectifying K+ channel with a larger inward
      conductance of 65 pS and outward conductance of 15 pS in the on-cell
      configuration. In this channel, rectification was due to the block of outward
      currents by Mg2+ and Ca2+ ions, since when both ions were removed from the
      cytosolic side in inside-out patches the conductance of the channel was nearly
      ohmic. In contrast to the small-conductance channel, the swelling-activated
      channel was observed also in the presence of barium in the pipette. Neither type
      of channel was dependent on the presence of Ca2+ ions on the cytosolic side for
      activity.

PMID- 9569250
TI  - The CFTR chloride channel: nucleotide interactions and temperature-dependent
      gating.
AB  - The gating cycle of CFTR (Cystic Fibrosis Transmembrane conductance Regulator)
      chloride channels requires ATP hydrolysis and can be interrupted by exposure to
      the nonhydrolyzable nucleotide AMP-PNP. To further characterize nucleotide
      interactions and channel gating, we have studied the effects of AMP-PNP, protein
      kinase C (PKC) phosphorylation, and temperature on gating kinetics. The rate of
      channel locking increased from 1.05 x 10(-3) sec-1 to 58.7 x 10(-3) sec-1 when
      AMP-PNP concentration was raised from 0.5 to 5 mM in the presence of 1 mM MgATP
      and 180 nM protein kinase A catalytic subunit (PKA). Although rapid locking
      precluded estimation of Po or opening rate immediately after the addition of AMP
      PNP to wild-type channels, analysis of locking rates in the presence of high AMP
      PNP concentrations revealed two components. The appearance of a distinct, slow
      component at high [AMP-PNP] is evidence for AMP-PNP interactions at a second
      site, where competition with ATP would reduce Po and thereby delay locking. All
      channels exhibited locking when they were strongly phosphorylated by PKA, but not
      when exposed to PKC alone. AMP-PNP increased Po at temperatures above 30 degrees
      C but did not cause locking, evidence that the stabilizing interactions between
      domains, which have been proposed to maintain CFTR in the open burst state, are
      relatively weak. The temperature dependence of normal CFTR gating by ATP was
      strongly asymmetric, with the opening rate being much more temperature sensitive
      (Q10 = 9.6) than the closing rate (Q10 = 3.6). These results are consistent with
      a cyclic model for gating of phosphorylated CFTR.

PMID- 9569252
TI  - The Science and Practice of Pediatric Cardiology

PMID- 9569251
TI  - Characterization of the stretch-activated chloride channel in isolated human
      atrial myocytes.
AB  - Macroscopic and unitary currents through stretch-activated Cl- channels were
      examined in isolated human atrial myocytes using whole-cell, excised outside-out
      and inside-out configurations of the patch-clamp technique. When K+ and Ca2+
      conductances were blocked and the intracellular Ca2+ concentration ([Ca2+]i) was
      reduced, application of positive pressure via the pipette activated membrane
      currents under whole-cell voltage-clamp conditions. The reversal potential of the
      current shifted by 60 mV per 10-fold change in the external Cl- concentration,
      indicating that the current was Cl- selective. The current was inhibited by bath
      application of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 9
      anthracenecarboxylic acid (9-AC). beta-Adrenergic stimulation failed to activate
      a Cl- current. In single channel recordings from outside-out patches, positive
      pressure in the pipette activated the unitary current with half-maximal
      activation of 14.7 mm Hg at +40 mV. The current-voltage relationship of single
      channel activity obtained in inside-out patches was linear in symmetrical Cl-
      solution with the averaged slope conductance of 8.6 +/- 0.7 pS (mean +/- SD, n =
      10). The reversal potential shift of the channel by changing Cl- concentration
      was consistent with a Cl- selective channel. The open time distribution was best
      described by a single exponential function with mean open lifetime of 80.4 +/-
      9.6 msec (n = 9), while at least two exponentials were required to fit the closed
      time distributions with a time constant for the fast component of 11.5 +/- 2.2
      msec (n = 9) and that for the slow component of 170.2 +/- 21.8 msec (n = 9).
      Major changes in the single channel activity in response to pressure were caused
      by changes in the interburst interval. Single channel activity was inhibited by
      DIDS and 9-AC in a manner similar to whole-cell configuration. These results
      suggest that membrane stretch induced by applying pressure via the pipette
      activated a Cl- current in human atrial myocytes. The current was sensitive to Cl
      channel blockers and exhibited membrane voltage-independent bursting opening
      without sensitive to beta-adrenergic stimulation.

PMID- 9569253
TI  - Historical Vignette: Patent Ductus Arteriosus

PMID- 9569254
TI  - The Pediatric Cardiology Handbook

PMID- 9569256
TI  - Upcoming Events in Pediatric Cardiology

PMID- 9569255
TI  - Historical Vignette: Congenital Aortic Stenosis

PMID- 9569257
TI  - The thymus: from past misconception to present recognition.
AB  - The critical role of the thymus in the development of the immune system was
      unknown until recently. For a long time physicians were puzzled by the presence
      of a large thymus in early life and attributed many symptoms to it. This review
      briefly covers the history of the thymus and its function as a primary lymphoid
      organ, along with a short background of the development of the immune system.
      Thymic diseases and their imaging features are also reviewed briefly.

PMID- 9569259
TI  - MR findings in pituitary haemosiderosis.
AB  - A girl with Diamond-Blackfan syndrome and hypopituitarism was suspected of having
      pituitary haemosiderosis because of the clinical picture and the long history of
      blood transfusions. On T1-weighted MR images the pituitary exhibited a markedly
      hypointense anterior lobe (mimicking the empty sella), suggesting iron
      deposition, while on T2W MRI the low signal of the pituitary was surrounded by
      the high signal of the CSF. MR may be considered the examination of choice for
      detecting iron overload in the pituitary.

PMID- 9569258
TI  - MRA of the intracranial circulation in asymptomatic patients with sickle cell
      disease.
AB  - BACKGROUND: MR angiography (MRA) provides a mechanism for non-invasively studying
      blood flow, thus providing a new opportunity to study the intracranial
      circulation in asymptomatic sickle cell disease (SCD) patients. Although
      conventional angiography is the gold standard for the depiction of vascular
      anatomy, this is too invasive for an asymptomatic population. OBJECTIVE: To
      establish the range of appearances in asymptomatic SCD patients and to correlate
      brain MRI results (either sub-clinical abnormalities or normal brain parenchyma)
      with the MRA findings. MATERIALS AND METHODS: Brain MRI and MRA of the
      intracranial circulation was performed on 22 patients (13 male and 9 female,
      median age 7.5 years, range 1.3-20 years). Fourteen were homozygous SS and eight
      were SC. The median haematocrit at the time of MRI was 25.9 (range 13.8-33.3).
      RESULTS: On MR imaging, four patients had infarcts in eight vascular territories
      (six anterior and two posterior). In 3/4 of anterior vascular territories with
      infarction, long ( >/= 6 mm) segments of abnormal signal were seen at the
      internal carotid artery bifurcation with associated reduced distal flow. Short
      focal areas of abnormal signal were commonly seen where vessels branched,
      bifurcated or curved and were not associated with infarcts. These areas probably
      represent turbulence-related dephasing secondary to high velocity flow found in
      SCD. CONCLUSION: Long segments ( >/= 6 mm) of abnormal signal with reduced distal
      flow correlated with sub-clinical infarction.

PMID- 9569260
TI  - Duplication of the pituitary gland in a newborn with median cleft face syndrome
      and nasal teratoma.
AB  - A newborn suffered immediate neonatal respiratory distress because of an
      obstructive, soft-tissue nasal mass. Clinical examination revealed a cleft palate
      with a protruding polypoid mass. CT and MRI showed a heterogeneous nasopharyngeal
      mass and associated intracranial abnormalities - duplication of the hypophysis
      and hypoplasia of the corpus callosum. Duplication of the hypophysis is a very
      rare malformation, only 13 cases having been previously described. The suggested
      pathogenesis is duplication of the prechordal plate and anterior end of the
      notochord during early embryological development.

PMID- 9569261
TI  - Gastric trichobezoar with gastric ulcer: MR findings 

PMID- 9569262
TI  - Sirenomelia with an uncommon osseous fusion associated with a neural tube defect.
AB  - A sireniform infant presented with an uncommon osseous fusion of the lower limbs
      characterised by a fused femur, a partially fused tibia and sympus dipus with
      rudimentary digits and metatarsals. Associated abnormalities included sacral
      agenesis, a deformed pelvis, anorectal atresia, renal agenesis, cystic renal
      dysplasia, agenesis of the uterus and urinary bladder, ambiguous external
      genitalia, a single umbilical artery, a lumbosacral neural tube defect, and
      ventriculomegaly secondary to a Chiari II malformation. The pathogenesis of
      concurrent sirenomelia and neural tube defect is discussed.

PMID- 9569263
TI  - Gastric trichobezoar with gastric ulcer: MR findings.

PMID- 9569264
TI  - Hyperechoic caudate nuclei: a potential mimic of germinal matrix hemorrhage.
AB  - BACKGROUND: We have encountered bilateral hyperechoic foci in the region of the
      germinal matrix on cranial sonograms in neonates that have an appearance similar
      to germinal matrix hemorrhage (GMH), but are unusual either due to the age of the
      patient at presentation or to the evolution of the foci on follow-up. We believe
      that these findings represent hyperechoic caudate nuclei (HCN) rather than GMH.
      OBJECTIVE: To demonstrate that bilateral HCN can be seen on cranial sonography in
      neonates and can mimic bilateral GMH. MATERIALS AND METHODS: The cranial
      sonograms were reviewed in nine neonates (three term and six premature) who had
      HCN identified on at least one sonographic examination. CT (two patients) and MR
      (one patient) studies were also reviewed, as well as the neuropathological
      examination in one patient who died and had an autopsy. The patients' medical
      records were reviewed to identify any clinical markers for significant risk of
      perinatal ischemia. RESULTS: There was clinical evidence for risk of ischemia in
      five of the nine neonates. All nine patients had bilateral HCN on the initial or
      follow-up studies. Small cysts were seen sonographically in two patients. CT was
      normal in one patient and revealed a small unilateral focus of increased
      attenuation in one infant (very small compared to the bilateral HCN). MR was
      normal in one patient. Histopathological examination of the brain was normal in
      the one patient who died and had an autopsy. CONCLUSION: Hyperechoic caudate
      nuclei can occur in neonates either as a normal finding, or possibly related to
      ischemia, and should not always be attributed to GMH.

PMID- 9569265
TI  - Intestinal rotational abnormalities in polysplenia and asplenia syndromes.
AB  - OBJECTIVE: To review the anomalies of intestinal rotation occurring in
      association with asplenia (right isomerism) and polysplenia (left isomerism)
      syndromes. MATERIALS AND METHODS: A retrospective study was performed of 27
      children with asplenia (21) or polysplenia (6) identified from the cardiology and
      radiology databases from 1988 to 1996 and in whom an upper gastrointestinal
      barium study had been performed. The intestinal rotation was determined by
      reviewing the barium meal and could be divided into four groups: (1) normal
      rotation, (2) incomplete rotation or nonrotation, (3) reversed rotation and (4)
      reversed incomplete rotation or nonrotation. Surgical correlation was obtained at
      laparotomy in 17 patients. RESULTS: Of the 27 children studied, 3 (11 %) had
      normal rotation; incomplete rotation or nonrotation occurred in 5 (19 %), and 2
      in this group developed midgut volvulus; 5 (19 %) had reversed rotation; 14 (52
      %) had reversed incomplete rotation or nonrotation. CONCLUSION: Asplenia and
      polysplenia are frequently associated with intestinal malrotation, and a barium
      study is recommended in all of these children, as many will be at risk of midgut
      volvulus.

PMID- 9569266
TI  - Magnetic resonance cholangiography--feasibility and application in the paediatric
      population.
AB  - OBJECTIVE: To assess the feasibility of magnetic resonance cholangiography (MRC)
      in paediatrics. MATERIALS AND METHODS: MRC was attempted in 41 children from 1
      week to 14-years. There were three groups: (1) children studied with MRI for non
      biliary problems as controls; (2) infants with jaundice; and (3) older children
      suspected of biliary disease. The examination was successfully performed in 35
      children, which included 12 children studied for non-biliary problems, 12 infants
      with jaundice, and 11 older children with suspected biliary disease. RESULTS: In
      group 1, the entire common duct was visualised in all 12 children. In group 2,
      successful demonstration of the common duct was achieved in two of the ten
      infants with subsequent confirmation of normal bile duct patency. In the last
      group of patients with suspected biliary disease, MRC gave good anatomical
      display of six choledochal cysts but failed to demonstrate the anomalous
      choledochopancreatic channel. It helped to confirm the diagnosis of two cases of
      pancreatic head cysts, and one case of Caroli's disease. CONCLUSION: MRC can be
      applied to the paediatric population, but its value depends on the type of
      problem to be evaluated. With current spatial resolution, its value in the
      diagnosis of biliary atresia is probably limited because it cannot reliably
      demonstrate the bile ducts in young infants with non-obstructive jaundice. In
      older children, it could provide a non-invasive anatomical display of the biliary
      tree and its disease. It has a potential role in addressing problematic cases
      encountered during ultrasonography.

PMID- 9569267
TI  - Primary Ewing's sarcoma of the sphenoid bone: a rare presentation.

PMID- 9569268
TI  - Retropsoas hernia as a cause of chronic abdominal pain: CT diagnosis.
AB  - Congenital retropsoas small bowel herniation is reported as the cause of long
      standing recurrent abdominal pain in a teenage girl. Knowledge of this entity is
      important for differential diagnosis of abdominal pain, mass, or retroperitoneal
      gas and fluid, and for avoiding complications of percutaneous renal
      interventions.

PMID- 9569269
TI  - CT appearances of the Rapunzel syndrome: an unusual form of bezoar and
      gastrointestinal obstruction.
AB  - The CT appearances of an unusual type of trichobezoar which causes the Rapunzel
      syndrome are described. This syndrome is characterized by intestinal obstruction
      secondary to a bezoar possessing a tail which extends to or beyond the ileo-cecal
      valve. Most cases of bezoar are diagnosed with plain films or barium meal, but CT
      may be requested in patients who present with abdominal masses. The Rapunzel
      syndrome may be diagnosed with a combination of the CT findings and the history.

PMID- 9569270
TI  - Malignant intraperitoneal neoplasms of childhood.
AB  - OBJECTIVE: The purpose of this paper is to review and categorize the CT
      appearances of primary and secondary intraperitoneal neoplasms in children.
      MATERIALS AND METHODS: We retrospectively reviewed the CT images of 14 cases of
      intraperitoneal neoplasms. They were reviewed for bowel wall thickening,
      mesenteric nodules, ascites, calcification, peritoneal nodules, omental caking,
      and contrast enhancement. RESULTS: Computed tomography images of 14 cases of
      intraperitoneal neoplasms were evaluated: rhabdomyosarcoma (5), lymphoma (3),
      neuroblastoma (2), germ cell tumor (1), mesothelioma (1), Wilms tumor (1), and
      hepatocellular carcinoma (1). Nodular enhancement was seen in all cases, ascites
      in most, significant bowel wall thickening only with lymphoma, and calcification
      only with germ cell tumors. Omental caking was present both with rhabdomyosarcoma
      and lymphoma. CONCLUSIONS: While rare in pediatrics, intraperitoneal neoplasms
      occur in children, and CT is useful in identifying these peritoneal neoplasms.

PMID- 9569271
TI  - MRI of extracranial masses in children: the usefulness of gadolinium-chelate
      enhancement.
AB  - OBJECTIVE: This study evaluated the usefulness of gadolinium (Gd) chelates in
      magnetic resonance imaging (MRI) of extracranial pediatric mass lesions.
      MATERIALS AND METHODS: Seventy-five MRI studies were obtained on 60 children
      (mean age 5.06 years) with pathologically proven mass lesions. Post-contrast T1
      weighted (T1W) images were compared with pre-contrast T1-weighted, T2-weighted
      (T2W) and both T1W and T2W images. They were evaluated for their ability to
      demonstrate lesion margins and extent, to add additional information, and to
      increase confidence in or change a diagnosis. In all patients post-contrast
      images were also evaluated for degree and pattern of enhancement. RESULTS:
      Malignant lesions enhanced much more intensely than benign lesions (P<0.0005).
      Lack of enhancement was seen only in benign lesions. A heterogeneous pattern of
      enhancement was more frequently seen in malignancy (P<0.05). Additional
      information was provided on Gd-enhanced T1W images in 36% of cases compared to
      unenhanced T1 and T2W images. Diagnostic confidence was improved in 29%. The Gd
      enhanced images changed the diagnosis correctly in 5% and incorrectly in 1%.
      CONCLUSION: Post-contrast images clarified specific issues, better defined lesion
      extent and margins in a majority of cases, and gave additional useful information
      in selected cases.

PMID- 9569272
TI  - Common bile duct obstruction caused by hydatid cyst membranes: US and CT imaging.

PMID- 9569273
TI  - Coexistence of an adrenocortical carcinoma with an abdominal ganglioneuroma in a
      child.
AB  - We report a 3-year, 5-month-old boy with an adrenocortical carcinoma. These
      tumours are rare and highly malignant in childhood. In most cases they are
      functional, secreting adrenocortical hormones. In this case there was a
      misleading coexistence with a second abdominal neoplasm, which was a
      ganglioneuroma; this is a rare benign tumour arising from the sympathetic nervous
      system. The imaging investigations and their findings are discussed and
      correlated with pathology.

PMID- 9569274
TI  - Extra-articular triplane fracture of the distal tibia: a case report.
AB  - The triplane fracture of the distal tibia is anatomically complex. It typically
      consists of a coronal fracture of the metaphysis, a transverse fracture of the
      physis, and a sagittal, intra-articular fracture of the epiphysis. We report an
      unusual variation of the triplane fracture which includes an extra-articular
      epiphyseal component involving the medial malleolus. This is an important variant
      to recognize because it does not disrupt the distal tibial articular surface.
      This lack of articular involvement allows for non-surgical management in contrast
      to the usual triplane fracture which often requires open reduction and internal
      fixation.

PMID- 9569275
TI  - Disk degenerative disease in childhood: Scheuermann's disease, Schmorl's nodes,
      and the limbus vertebra: MRI findings in 12 patients.
AB  - Twelve pediatric patients were studied with MRI. All had various disk problems
      including Scheuermann's disease, Schmorl's nodes and limbus vertebrae. All
      patients shared loss of disk height, altered disk hydration and variable
      herniation of nuclear material.

PMID- 9569276
TI  - Congenital chondromyxoid fibroma of the ethmoid: case report.
AB  - This report describes a congenital case of chondromyxoid fibroma (CMF) arising
      from the ethmoid bone. We believe it to be the second case of congenital CMF that
      has been documented, and the third case of CMF arising in the ethmoid. We
      describe the radiographic features of this rare entity and indicate the necessity
      for careful correlation between radiographic and histological findings to
      distinguish CMF from chondrosarcoma.

PMID- 9569277
TI  - Congenitally short trachea with compression of the left mainstem bronchus: MRI
      findings.
AB  - The MRI features of congenitally short trachea in a patient presenting with
      respiratory distress are presented. Compression of the left mainstem bronchus by
      the aortic arch, a recognised complication of this anomaly, could be demonstrated
      by MRI, obviating the need for other imaging modalities.

PMID- 9569278
TI  - Non-accidental pediatric pelvic fracture: a case report.
AB  - Few reports have documented pelvic fracture as a result of child abuse. We
      present a case with radiologic findings and pathologic correlation. Although
      documented patterns of osseous injury have been extensively described, a thorough
      skeletal evaluation must include a frontal view of the pelvis as well.

PMID- 9569279
TI  - In situ Characterization of Biofilm Exopolymers Involved in the Accumulation of
      Chlorinated Organics

PMID- 9569280
TI  - Microbial Abundance and Activity in a Low-Conductivity Aquifer System in East
      Central Texas

PMID- 9569281
TI  - Significance of Lysogeny in the Marine Environment: Studies with Isolates and a
      Model of Lysogenic Phage Production

PMID- 9569282
TI  - Heterotrophic Nanoflagellates, Bacteria, and Labile Organic Compounds in
      Continental Shelf and Deep-Sea Sediments of the Eastern Mediterranean

PMID- 9569283
TI  - Susceptibility of Bacteria in Estuarine Environments to Autochthonous
      Bdellovibrios

PMID- 9569284
TI  - Impacts of Carbon and Flooding on Soil Microbial Communities: Phospholipid Fatty
      Acid Profiles and Substrate Utilization Patterns

PMID- 9569285
TI  - Survival of Inoculants in Polluted Sediments: Effect of Strain Origin and Carbon
      Source Competition

PMID- 9569287
TI  - Effects of Decomposing Maize Litter on Community Level Physiological Profiles of
      Soil Bacteria

PMID- 9569286
TI  - Seasonal Patterns of Bacterial Abundance and Production in the Mississippi River
      Plume and Their Importance for the Fate of Enhanced Primary Production

PMID- 9569288
TI  - Fast and Accurate Identification of European Species of the Paramecium aurelia
      Complex by RAPD-Fingerprints

PMID- 9569289
TI  - The indeterminate renal mass.

PMID- 9569290
TI  - Atypical cystic renal masses.

PMID- 9569291
TI  - Renal neoplasms in patients with renal cystic diseases.

PMID- 9569292
TI  - Renal oncocytomas.

PMID- 9569293
TI  - The small renal mass: detection, characterization, and management.

PMID- 9569294
TI  - Secondary renal neoplasms.

PMID- 9569295
TI  - Ultrasonographic evaluation of the cervical lymph nodes in preoperative staging
      of esophageal neoplasms.
AB  - BACKGROUND: The detection of cervical lymph node metastases plays an important
      role in staging of patients affected by esophageal cancer to perform the best
      therapeutic approach. METHODS: We report our experience concerning the ultrasound
      evaluation of the cervical area in 174 patients with esophageal cancer.
      Ultrasonographic evaluation of the neck can be done with a 7.5- or 10 MHz
      transducer in all cases, with selective scanning of the lymph node chains of the
      internal jugular veins and supraclavicular regions. The short-to-long axis ratio
      (S/L) was a useful way to detect lymph node metastasis. Histopathologic diagnoses
      were obtained by sonographically guided fine-needle aspiration biopsy. RESULTS:
      At ultrasound examination, we found 18 (10.3%) patients with metastatic cervical
      nodes. Of these, 17 (94.4%) had metastatic cervical lymph nodes confirmed by
      cytology from fine-needle biopsy. Lymph node exceeding 5 mm in long axis and with
      an S/L over 0.5 showed a higher incidence of metastasis than those with an S/L
      under 0.5. Our experience shows a high incidence of lymph node metastases in
      patients with esophageal cancer localized to the thoracic supracarinal tract and
      in patients with cervical and lower esophageal cancer. CONCLUSION: In the
      ultrasound evaluation of nodes, the most useful parameters are size of nodes,
      heterogeneity of internal echoes, morphology of the margins, and the deformation
      caused by compressive instrumental manipulation. These criteria, indicated by the
      Japanese Society for Esophageal Diseases, yield a high sensitivity and diagnostic
      specificity when the ultrasonographic studies are performed.

PMID- 9569296
TI  - Bilateral paraduodenal hernias: computed tomography and magnetic resonance
      imaging appearance.
AB  - Paraduodenal hernias are rare congenital malformations. We report an unusual case
      of bilateral paraduodenal hernias diagnosed preoperatively by small bowel series,
      computed tomography (CT), and magnetic resonance imaging (MRI). Both CT and MRI
      are useful in the noninvasive diagnosis of paraduodenal hernias.

PMID- 9569297
TI  - Use of methylcellulose in small bowel follow-through examination: comparison with
      conventional series in normal subjects.
AB  - BACKGROUND: To evaluate and optimize a modified small bowel follow-through
      examination (SBFT) by using an oral administration of a large amount (600 mL) of
      methylcellulose after taking a small amount of barium. METHODS: Ninety-nine
      normal subjects underwent modified SBFT with an oral administration of 600 mL of
      0.5% methylcellulose after taking 100 mL of 120% or 100, 150, or 200 mL of 70%
      w/v barium. The transradiancy and distensibility of the bowel and the transit
      time were compared with those of 39 other normal subjects who underwent
      conventional SBFT with 500 mL of 70% w/v barium. RESULTS: Except for two subjects
      who developed diarrhea immediately after examination, no patients complained of
      acute symptoms, such as abdominal pain or vomiting. Modified SBFT was much
      superior to conventional series for obtaining good bowel transradiancy and rapid
      transit time (range = 37-49 min), but bowel distention was not significantly
      improved. The use of 150 mL of 70% w/v barium was better than the other three
      modified techniques for achieving good bowel transradiancy, rapid transit time,
      and less occurrence of flocculation. CONCLUSION: Modified SBFT is a simple method
      for easily improving the image quality in terms of bowel transradiancy and
      transit time.

PMID- 9569298
TI  - Eosinophilic gastroenteritis: percutaneous biopsy under ultrasound guidance.
AB  - Eosinophilic gastroenteritis (EG) is an unusual disorder that is characterized by
      diffuse or scattered eosinophilic infiltration of the digestive tract. The
      diagnosis is based on histology obtained by capsule, endoscopic, laparoscopic, or
      laparotomy biopsy. The eosinophilic infiltration produces thickening of the small
      bowel wall that can be observed by using sonography. The appearance produces the
      pseudokidney sign that can be used to guide biopsy. We report the first case of
      EG diagnosed by percutaneous biopsy under ultrasound guidance.

PMID- 9569299
TI  - Double-contrast barium enema examination as performed by radiographers.

PMID- 9569300
TI  - Mucocele of the appendix: ultrasonographic and CT findings.
AB  - BACKGROUND: Mucocele of the appendix is a rare disease entity, but preoperative
      diagnosis is very important. With the advent of ultrasonography (US) and computed
      tomography (CT), it has been possible to preoperatively diagnose mucocele of the
      appendix. We describe the spectrum of US and CT findings of mucocele of the
      appendix and the differential points from mimicking diseases. METHODS: We
      evaluated 17 patients with pathologically proven mucocele of the appendix by
      using US and CT. Pathologic diagnoses of 17 patients were mucinous cystadenoma in
      11 patients, mucinous cystadenocarcinoma in two, and mucosal hyperplasia in four.
      We analyzed morphologic characteristics of mucocele of the appendix at US and CT.
      RESULTS: The typical US finding were a cystic mass with variable internal
      echogenicity, layered wall, and calcification in the wall. The CT finding was a
      well-encapsulated cystic mass with a wall of variable thickness. Both cases with
      focal nodular solid enhancing portion in the wall on CT were pathologically
      proven as mucinous cystadenocarcinoma. CONCLUSION: US and CT were useful methods
      in diagnosing mucocele of the appendix and differentiating this condition from
      mimicking diseases. Nodular enhancing lesion in the wall of the mucocele may be a
      finding suggestive of malignant cause of mucocele.

PMID- 9569302
TI  - Examination techniques for endosonography of the anal canal.
AB  - BACKGROUND: To determine whether patient position or sphincter contraction
      influences sphincter thickness or defect assessment. METHODS: Anal endosonography
      was performed on 35 consecutive patients (30 women, five men). Twenty-five were
      scanned in the left lateral and prone positions, and the internal sphincter
      thickness was measured. In 10 patients, the internal sphincter, longitudinal
      muscle, external sphincter, and length of any defect were measured at rest and
      during anal squeeze. RESULTS: There was no significant difference in internal
      sphincter thickness measured in the prone and left lateral positions (95% limits
      of agreement, -0.12 to 0.06). The thickness of the internal sphincter,
      longitudinal muscle, and external sphincter at rest did not change significantly
      during straining (95% limits of agreement, -0.44 to 0.3, -0.28 to 0.24, and 0.33
      to 0.71, respectively). The squeeze maneuver did not influence defect appearance
      or length (95% limits of agreement, -2.845 to 2. 379). Greater symmetry of the
      anterior part of the external sphincter and improved visualization of perineum
      was achieved in the prone position. CONCLUSION: Examination in the prone position
      is preferred. Squeeze maneuvers are of no diagnostic benefit.

PMID- 9569301
TI  - Urinary excretion of orally ingested gastrografin on CT.
AB  - Renal excretion of orally ingested gastrografin has rarely been reported on
      computed tomography (CT). We studied the unenhanced scans of 82 patients with
      bowel disorders or perforation to assess the prevalence of urinary contrast
      material (CM) in various bowel diseases. We also assessed the clinical
      significance of this sign. In addition, we reviewed the unenhanced CT scans of
      100 randomly selected patients without bowel diseases as a control group. Twenty
      nine of the 58 patients with bowel diseases, six of nine with free perforation,
      and one of 15 with covered perforation had CM in the urinary tract. None of the
      100 without bowel disease showed urinary CM. Statistical analysis was done by
      using the Fisher's exact test. The prevalence of urinary CM was highest in
      inflammatory bowel disease, radiation enteritis, and free perforation (p < 0.
      0001). This study shows that the CT finding of orally ingested gastrografin in
      the urinary tract differentiates patients with bowel disease from those without.

PMID- 9569304
TI  - Delayed MR imaging of the liver: correlation of delayed enhancement of hepatic
      tumors and pathologic appearance.
AB  - BACKGROUND: The value of delayed magnetic resonance (MR) imaging (6 min) and
      ultradelayed MR imaging (1-4 h) for differentiating of hepatic tumors was
      studied. METHODS: Postcontrast delayed and ultradelayed MR images were obtained
      after administration of 0.1 mmol/kg of Gd-DTPA in 30 patients with various
      malignant hepatic tumors. RESULTS: Delayed enhancement in the center of the
      tumors was seen in 13 patients on the delayed MR images and in 22 patients on the
      ultradelayed MR images. On the ultradelayed images, peripheral hypointense rim
      was seen in 12 patients and central focal hypointense area was seen in eight
      patients. Pathologically, the portion showing delayed enhancement corresponded to
      abundant fibrous stroma, the hypointense rim to rich proliferation of tumor
      cells, and the central hypointense areas to coagulative necrosis. CONCLUSION:
      Ultradelayed MR imaging can characterize different tissue components within
      various hepatic tumors.

PMID- 9569303
TI  - CTAP in budd-chiari syndrome: evaluation of intrahepatic portal flow.
AB  - BACKGROUND: To assess the intrahepatic portal flow in patients with Budd-Chiari
      syndrome (BCS) by computed tomography (CT) during arterial portography (CTAP).
      METHODS: Five patients with BCS [with (n = 3) and without (n = 2) inferior vena
      cava (IVC) obstruction] underwent both CTAP and postcontrast CT following CTAP.
      CTAP and postcontrast CT after angioplasty were also performed in one patient.
      Findings on CTAP and postcontrast CT were analyzed retrospectively. RESULTS:
      Patients with IVC obstruction and a patent large hepatic vein showed homogeneous
      hepatic enhancement on CTAP. Patients without IVC obstruction and with no patent
      large hepatic veins showed heterogeneous hepatic enhancement, which consisted of
      patchy enhancement and more definite enhancement in the central part of the
      liver. On postcontrast CT, the patchy enhancement was enlarged compared with that
      on CTAP in these patients. The heterogeneous hepatic enhancement became
      homogeneous in the patient who underwent angioplasty. CONCLUSION: We suggest that
      the more marked the blood congestion, the more heterogeneous the hepatic
      enhancement becomes on CTAP. Heterogeneous hepatic enhancement on CTAP is seen in
      such cases without any patent hepatic veins.

PMID- 9569305
TI  - Cryotherapy of metastatic carcinoid tumors.
AB  - BACKGROUND: To describe the use of hepatic cryotherapy to treat patients with
      symptomatic carcinoid metastates. METHODS: Hepatic cryotherapy was performed on
      five patients with carcinoid syndrome resulting from metastatic carcinoid tumors.
      Intraoperative ultrasound was used to guide the cryotherapy and to assess the
      adequacy of freezing. RESULTS: All five patients had relief of the carcinoid
      syndrome after treatment. In four of the five patients, the relief was prolonged
      (>3 months); in one patient, the relief of symptoms was transient (2 months).
      Four of five patients had a transient reduction in hormonal tumor markers (the
      fifth patient did not have hormonal-level follow-up). During a follow-up period
      of 2.5 years, four of the five patients died. The 6-month survival rate was 80%,
      the 1-year survival rate was 60%, the 2-year survival rate was 40%, and the 2.5
      year survival was 20%. One patient is alive 30 months after treatment.
      CONCLUSION: Hepatic cryotherapy can provide symptomatic relief for patients with
      hepatic metastates producing the carcinoid syndrome.

PMID- 9569306
TI  - Pseudoaneurysm secondary to pancreatitis presenting as GI bleeding.
AB  - Pseudoaneurysm formation is a rare but potentially dev approximately astating
      complication of pancreatitis. It can be diag approximately nosed by using various
      imaging modalities including computer tomography, ultrasound, and angiography and
      should be entertained in any patient with a history of pancreatitis. We present
      the imaging findings in three patients with pseudoaneurysm formation secondary to
      pancreatitis who initially presented with gastrointestinal bleeding.

PMID- 9569307
TI  - Modified intra-arterial calcium stimulation with venous sampling test for
      preoperative localization of insulinomas.
AB  - BACKGROUND: To determine the accuracy and safety of a modified intra-arterial
      calcium stimulation with the venous sampling test (ASVS) for preoperative
      localization of insulinomas. Modification included stimulation with a fixed low
      dose of calcium gluconate, additional stimulation in the distal splenic artery,
      and no insulin sampling in the left hepatic vein. METHODS: In 10 patients showing
      biochemical evidence of organic hyperinsulinemia, 0.45 mmol of Ca2+ was injected
      into the gastroduodenal, superior mesenteric, proper hepatic, proximal, and
      distal splenic arteries during angiography. Insulin levels were measured in
      samples taken from the right hepatic vein before and 30, 60, 90, 120, 180, and
      300 s after Ca2+ injection. RESULTS: Insulin gradients with an increase of more
      than fourfold indicated direct tumor supply, two- to fourfold correlated with
      collateral supply, and less than twofold correlated with normal tissue
      vascularization. ASVS localized all the adenomas of the pancreatic head (n = 3)
      and body (n = 2) and two of four adenomas of the tail correctly, as confirmed by
      surgery. Two adenomas of the proximal pancreatic tail were erroneously localized
      to the body segment, but the fault was rectified by angiography. In one patient
      with a negative ASVS and without exploration, the diagnosis of an insulinoma was
      revised. CONCLUSION: ASVS with a fixed low dose of calcium gluconate is a highly
      accurate and safe method for preoperative localization of insulinomas. Sampling
      in the left hepatic vein can be routinely omitted. Additional stimulation in the
      distal splenic artery seems helpful in surgical decision making, but additional
      experience is needed.

PMID- 9569308
TI  - CT appearance of ectopic pancreas: a case report.
AB  - The appearance of ectopic pancreas on computed tomography (CT) is described in a
      47-year-old man with bowel obstruction. The enhancement pattern of ectopic
      pancreas after intravenous iodine contrast administration is the same as that of
      leiomyoma or carcinoid. This CT finding has not been reported previously to our
      knowledge.

PMID- 9569309
TI  - The query corner.

PMID- 9569312
TI  - Abstracts of selected papers from the current literature 

PMID- 9569310
TI  - Combined CT during the arterial portography and CT arteriography.

PMID- 9569315
TI  - Non-invasive imaging of abdominal vascular pathologies.
AB  - With the advent of ultrasound (US), Doppler and color-flow Doppler imaging,
      computed tomography (CT), and magnetic resonance angiography (MRA) the ability
      for non-invasive studies of the abdominal vasculature has been enhanced
      considerably. In this paper an overview on various abdominal vascular pathologies
      is presented. Because of the dramatic improvements in image quality, special
      emphasis is given on the potential role of breathhold contrast-enhanced three
      dimensional (3D) MRA which appears to be a versatile non-invasive alternative to
      conventional angiography.

PMID- 9569316
TI  - Non-invasive vascular imaging: assessing tumour vascularity.
AB  - Non-invasive assessment of vascularity is a new diagnostic approach to
      characterise tumours. Vascular assessment is based on the pathophysiology of
      tumour angiogenesis and its diagnostic implications for tumour biology, prognosis
      and therapy response. Two current techniques investigating vascular features in
      addition to morphology are Doppler ultrasonography and contrast-enhanced MRI.
      Diagnostic differentiation has been shown to be possible with Doppler, and a high
      degree of observed vascularity could be linked to an aggressive course of the
      disease. Dynamic MRI using gadolinium chelates is already used clinically to
      detect and differentiate tumours. The histological correlation shows that
      capillary permeability is increased in malignant tumours and is the best
      criterion for differentiation from benign processes. Permeability and perfusion
      factors seem to be more diagnostic than overall vessel density. New clinical
      applications are currently being established for therapy monitoring. Further
      instrumental developments will bring harmonic imaging in Doppler, and faster
      imaging techniques, higher spatial resolution and novel pharmacokinetic concepts
      in MRI. Upcoming contrast agents for both Doppler and MRI will further improve
      estimation of intratumoural blood volume and vascular permeability.

PMID- 9569317
TI  - MR-based assessment of vascular morphology and function.
AB  - Initially, time-of-flight angiography found its way into clinical routine for
      imaging vascular morphology. In conjunction with phase-contrast imaging,
      functional and morphological assessment of vascular pathology became possible.
      The flow dependence and associated artifacts inherent to these techniques have
      restricted the clinical use of these magnetic resonance angiography (MRA)
      techniques to the extra- and intracranial arterial, as well as the systemic and
      portal, venous systems. With the advent of high-performance gradient systems a
      new, promising MRA strategy has been developed: contrast-enhanced 3D MR
      angiography. It is based on the combination of rapid 3D imaging and the T1
      shortening effect of intravenously infused paramagnetic contrast. This review
      provides a technical overview and critically discusses the clinical application
      for the different MRA techniques regarding morphological as well as functional
      assessment of the vascular system.

PMID- 9569318
TI  - Magnetic resonance imaging of congenital abnormalities of the thoracic aorta.
AB  - This article outlines the ability of MR imaging in the detection and presurgical
      evaluation of congenital abnormalities of the thoracic aorta (CATA). Congenital
      abnormalities of the thoracic aorta may be found incidentally on chest
      radiographs in patients without symptoms, or it can be associated with clinical
      findings which are very variable depending on the association with congenital
      cardiac malformations or vascular ring. When CATA is suspected as the cause of
      anomalies in the mediastinum in asymptomatic patients, confirmation of the
      abnormality should be by MR imaging allowing precise evaluation of the thoracic
      aorta and origin of the principal arteries. When CATA is considered because
      clinical findings indicate coarctation of the aorta, vascular ring or associated
      cardiac disorder, evaluation with ultrasound can be complemented by MR, which in
      most cases will replace the diagnostic catheterization.

PMID- 9569319
TI  - Abdominal Takayasu's arteritis: imaging with color duplex sonography.
AB  - Takayasu's arteritis is a inflammatory process of unknown etiology affecting
      mainly the thoracic and abdominal aorta and producing steno-occlusive findings of
      various degrees in different sites. We present a case of Takayasu's disease in a
      young woman, studied by color duplex sonography and verified by angiography.

PMID- 9569320
TI  - A case of spontaneous hemorrhage of the abdominal wall caused by rupture of a
      deep iliac circumflex artery treated by transcatheter arterial embolization.
AB  - We report an uncommon case of spontaneous massive hemorrhage of the abdominal
      wall caused by rupture of a deep iliac circumflex (DIC) artery. Enhanced computed
      tomography (CT) demonstrated a marked extravasation in a huge hematoma of the
      abdominal wall. Although a pelvic arteriogram demonstrated no extravasation, a
      superselective DIC arteriogram subsequently revealed an extravasation of the
      artery. We successfully performed transcatheter arterial embolization for the
      artery. There have been few reports in the literature of spontaneous hemorrhage
      in the abdominal wall resulting from rupture of DIC artery, which were defined by
      diagnostic imaging and successfully treated by transcatheter arterial
      embolization.

PMID- 9569321
TI  - Blunt abdominal trauma in adults: role of CT in the diagnosis and management of
      visceral injuries. Part 1: liver and spleen.
AB  - Computed tomography is now widely used in the initial diagnostic workup of adult
      trauma victims with suspected intra-abdominal injuries. We review the role of CT
      in the detection and management of blunt visceral injuries in two parts. In the
      first part we discuss general aspects of performing CT in the setting of
      abdominal trauma and the diagnostic findings of intra-abdominal hemorrhage and
      blunt hepatic and splenic injuries. Hepatic and splenic injuries can be detected
      by means of CT with a high accuracy. The vast majority of hepatic injuries can be
      successfully managed conservatively, even when CT demonstrates parenchymal damage
      of more than three segments and major hemoperitoneum. Delayed complications, e.
      g., formation of biloma or a false aneurysm, can be readily detected on repeat CT
      studies, although they are quite uncommon. The outcome of conservative treatment
      of splenic injuries remains unpredictable because delayed splenic rupture may
      occur even when initial CT shows only minor parenchymal lesions and little or no
      intraperitoneal hemorrhage.

PMID- 9569322
TI  - Virtual endoscopy of the small bowel: phantom study and preliminary clinical
      results.
AB  - The purpose of this study was to determine the optimal scanning technique for
      lesion detection in a small bowel phantom and to evaluate the virtual endoscopy
      (VE) technique in patients. A small bowel phantom with a fold thickness of 7 mm
      and length of 115 cm was prepared with nine round lesions (3 x 1 mm, 2 x 2 mm, 2
      x 3 mm, 2 x 4 mm). Spiral CT parameters were 7/7/4, 3/5/2, 3/5/1, 1.5/3/1 (slice
      thickness/table feed/reconstruction interval). VE was done using volume rendering
      technique with 1 cm distance between images and 120 degrees viewing angle. Two
      masked readers were asked to determine the number and location of the lesions.
      Seven patients underwent an abdominal CT during one breathhold after placement of
      a duodenal tube and filling of the small bowel with methyl cellulose contrast
      solution. VE images were compared with the axial slices with respect to
      detectability of pathology. With the 7/7/4 protocol only the 4-mm lesions were
      visualised with fuzzy contours. The 3/5/2 protocol showed both 4-mm lesions, one
      3-mm lesion and one false positive lesion. The 3/5/1 protocol showed both 4-mm
      and both 3-mm (one uncertain) lesions with improved sharpness, and no false
      positive lesions. One 2-mm and one 1-mm lesion were additionally seen with the
      1.5/3/1 protocol. Path definition was difficult in sharp turns or kinks in the
      lumen. In all patients, no difference was found between VE and axial slices for
      bowel pathology; however, axial slices showed 'outside' information that was not
      included in VE. We conclude that the 3/5/2 protocol may be regarded as an optimal
      compromise between lesion detection, coverage during one breathhold, and number
      of reconstructed images in patients; round lesions of 4 mm in diameter can be
      detected with high certainty.

PMID- 9569323
TI  - Umbilical hernia of stomach.
AB  - Herniation of the stomach through the umbilicus is exceedingly rare with only one
      case reported in the international literature in the past 40 years. One case of a
      reducible gastric umbilical hernia, not diagnosed by endoscopy, is reported.
      Diagnosis was made by double-contrast barium examination after 5 years of
      symptoms and ineffective treatment. Herniation of the stomach is difficult to
      diagnose by endoscopy and radiological studies can be more sensitive and allow a
      more specific diagnosis.

PMID- 9569324
TI  - An unusual localization of massive portasystemic collaterals: CT angiographic
      demonstration.
AB  - This article presents a patient with portal hypertension in whom an unusual
      localization for portosystemic collaterals have incidentally been found. Upper
      abdominal sonography revealed tubular structures filling the whole perirenal and
      partially the perihepatic area, and their venous nature was demonstrated with
      duplex Doppler sonography. Spiral CT angiography identified the right-sided
      retroperitoneal location and mesenteric-lumbar route of the collaterals. Upper
      gastrointestinal endoscopy with antral biopsy and percutaneous liver biopsy were
      performed. Laboratory results and specimen evaluation revealed chronic active
      hepatitis due to hepatitis-B infection. Attention is drawn to the abnormal
      location of these vessels, together with the noninvasive nature and competence of
      CT angiography in demonstrating vascular pathologies.

PMID- 9569325
TI  - MR imaging of anorectal malformations and associated anomalies.
AB  - Congenital anorectal malformations are found in many forms, and are frequently
      associated with other anomalies, especially of the spinal cord, spine, and
      urogenital system. Decisions concerning initial management of children with
      anorectal malformations can be made only after accurate determination of (a) the
      level and type of malformation, (b) the type of fistula, (c) the developmental
      state of the sphincter muscle complex, and (d) the presence of associated
      anomalies. Magnetic resonance imaging has proven to be the only modality to
      answer all these crucial questions, and has contributed to a better insight in
      the morphology and pathogenesis of such complex congenital malformations.

PMID- 9569326
TI  - Ganglioneuroma: an 'incidentaloma' of childhood.
AB  - In adults clinically silent adrenal masses can be discovered incidentally in
      imaging studies. Most of these 'incidentalomas' are benign, non-functioning
      adenomas. In contradistinction, in infancy and childhood the most common adrenal
      mass is the neuroblastoma, a malignant neural crest tumour. Four children are
      described, each with a benign neural crest tumour - ganglioneuroma - incidentally
      discovered by conventional radiography or sonographic examination. Complete
      surgical excision resulted in total recovery of all the children.

PMID- 9569327
TI  - A mild form of Proteus syndrome.
AB  - Proteus syndrome is a rare congenital hamartomatous syndrome. We report on the
      clinical and radiological appearances of a boy in order to illustrate the typical
      signs which include subcutaneous masses, in mild forms partial gigantism of hands
      and feet, hemihypertrophy, and bony abnormalities. We discuss how to make the
      definitive diagnosis on the basis of using a known rating scale, important
      aspects of differential diagnosis and clinical features, and diagnostic
      management.

PMID- 9569329
TI  - MR guidance of laser disc decompression: preliminary in vivo experience.
AB  - The purpose of this study was to perform percutaneous laser disc decompression
      (PLDD) under MR guidance in an open configuration 0. 5-T MR system. Following
      failed conservative treatment for 6 months, eight patients with contained disc
      herniations were enrolled in the study. Following MR guided introduction of the
      laser fiber into the targeted disc space, the laser-induced temperature
      distribution was visualized using a color-coded subtraction technique based on a
      T1-weighted GRE sequence. In seven patients PLDD could be performed. In all cases
      laser effects were depicted by MR. In this regard the color-coded technique was
      found to be superior to conventional magnitude images. Whereas no apparent
      decrease in the extent of herniation was discovered immediately following PLDD,
      T2-weighted FSE images showed signal intensity alterations in two of the seven
      patients. Clinical evaluation, obtained 3-4 months after PLDD, revealed a fair (n
      = 2) or good (n = 4) response to the treatment. One patient showed no change in
      symptoms. MR guidance and monitoring of PLDD is feasible within an open 0.5-T
      system and seems to render PLDD more safe and controllable.

PMID- 9569328
TI  - Granulomatous hepatitis in pasteurella multocida infection.
AB  - Numerous diseases can lead to multilocular lesions of the liver. The authors
      report a rare pediatric case of hepatic granulomas due to Pasteurella multocida:
      a 7-year-old girl with chronic fever was investigated by sonography and CT scan,
      demonstrating mesenteric lymph node enlargement and numerous small hepatic
      lesions. After surgical biopsy, histopathology of the liver specimens showed
      pyogenic granuloma, with serologic testing positive for Pasteurella multocida.
      Treatment with a tetracycline and corticosteroids was successful. Pasteurella
      multocida infection, despite its habitual benign course, should be suspected
      among differential diagnoses of lymphogranulomatous affections with hepatic
      involvement. No case of liver and lymph node foci in a child has been previously
      described.

PMID- 9569330
TI  - Longitudinal stress fractures of the tibia: comparative study of CT and MR
      imaging.
AB  - The aim of this study was to compare the performance of CT and MRI in the
      diagnosis of longitudinal stress fracture of the tibia (LSFT). A retrospective
      study of imaging findings was performed in 15 patients with LSFT. The CT and MR
      images were compared for detection of fracture line, callus, bone marrow edema,
      and soft tissues changes. The CT and MRI techniques allowed the detection of the
      fracture line in 82 and 73 % of cases, respectively. The callus was always
      visualized with CT or MRI. The MRI technique had a markedly higher sensitivity
      than CT in the detection of bone marrow edema (73 vs 18 %) and soft tissue
      lesions (87 vs 9 %). This may cause a misleading aggressive appearance on MRI.
      Computed tomography remains the best imaging modality for diagnosis of LSFT.
      However, MRI findings should be known to obviate the performance of CT or bone
      biopsy.

PMID- 9569331
TI  - Unilateral femoral deformity due to a focal fibrous tether.
AB  - The purpose of this paper is to assess the radiological features of the
      unilateral angular deformity of the distal end of the femur secondary to a focal
      fibrous tether. Only five cases of this entity have been reported in the
      literature. We report another two patients. Magnetic resonance study was
      performed on one of them, which has not been used in previous cases. Both cases
      are described with illustrations of the typical radiographic appearances
      supplemented by CT and MR imaging.

PMID- 9569332
TI  - Skeletal involvement and follow-up in linear nevus sebaceous syndrome.
AB  - Linear nevus sebaceous syndrome is a rare neurocutaneous syndrome in which
      associated radiographic findings of the peripheral skeletal system are uncommon.
      We report a follow-up study of a patient with mainly unilateral changes of the
      skeletal system involving the thorax and the right arm and leg.

PMID- 9569333
TI  - Pulmonary nodules: detection with low-dose vs conventional-dose spiral CT.
AB  - The purpose of the study was the evaluation of low-dose spiral CT in the
      detection and assessment of contours of pulmonary nodules. In a prospective
      investigation 71 consecutive chest CT examinations were acquired both at 30 and
      200 mA. Films were interpreted independently by two radiologists. According to
      the size, nodules were divided into four categories: </= 3, 4-5, 6-10, and > 10
      mm; nodule shape was registered. With both protocols, 240 nodules were detected.
      The correlation coefficient for both methods was 0.89. Discrepancies were found
      most frequently in nodules near to pulmonary vessels. Nodule size estimation did
      not differ more than one size category. Eight spiculated nodules were identified
      by both techniques. Low-dose spiral CT of the chest has a high sensitivity in the
      detection of pulmonary nodules. If clinical circumstances require dose
      minimization, low-dose spiral CT may be advocated as an alternative screening
      method to conventional dose spiral CT.

PMID- 9569334
TI  - Diagnosis of lung cancer in a patient with pneumoconiosis and progressive massive
      fibrosis using MRI.
AB  - We report the MRI features and correlative pathologic findings of a lung cancer
      in a patient with progressive massive fibrosis (PMF). In this case, MRI was able
      to distinguish the lung cancer as a high signal intensity area, and the fibrotic
      mass as a low signal intensity area, on both T1-weighted and T2-weighted images
      when compared with muscle. MRI is potentially useful in distinguishing cancer
      tissue from PMF in patients with pneumoconiosis.

PMID- 9569335
TI  - Imaging findings of central nervous system neuroepithelial cysts.
AB  - Neuroepithelial cysts are rare and mostly asymptomatic cerebrospinal fluid (CSF)
      like cysts. We describe herein the imaging findings in five patients with
      neuroepithelial cysts. Two cases of proven and three of presumed neuroepithelial
      cysts are presented. Three of five are located in the thalamus, a location which
      is not characteristic for neuroepithelial cysts. In the case of incidental
      finding of asymptomatic neuroepithelial cyst, clinical and radiological follow-up
      is indicated and surgical intervention is not necessarily warranted.

PMID- 9569337
TI  - Interhemispheric lipoma associated with subcutaneous lipoma.
AB  - We report an extremely rare case of intracranial lipoma that was associated with
      subcutaneous lipoma situated on the anterior fontanelle. During ultrasonographic
      examination of the subcutaneous lesion, intracranial lipoma was incidentally
      diagnosed. Computed tomography revealed corpus callosum agenesis,
      interhemispheric lipoma extending into the choroid plexus. Magnetic resonance
      imaging demonstrated the subcutaneous lipoma and also the exact extent of the
      lesion. The pathogenesis of lipomas is discussed and the literature is reviewed.

PMID- 9569336
TI  - Radiologic and histopathologic findings in a rare case of complex occult spinal
      dysraphism with association of a lumbar fibrolipoma, neurenteric cyst and
      tethered cord syndrome.
AB  - We present the case of a 60-year-old farmer who reported non-specific back pains
      for the past 30 years. Increasing paralysis of the left leg led to
      hospitalization. A complex occult spinal dysraphism comprising a fibrolipoma of
      the conus medullaris, an neurenteric cyst, and a tethered cord syndrome was
      diagnosed and operated on. The radiological and histological findings are
      demonstrated.

PMID- 9569338
TI  - Middle interhemispheric fusion.
AB  - We report a case of a 19-year-old woman with seizures and mental deficiency
      attributed to perinatal anoxia. Brain MR showed a congenital malformation, a rare
      form of semilobar holoprosencephaly termed middle interhemispheric fusion.

PMID- 9569339
TI  - Mammographic and ultrasonographic findings in bilateral breast cancer: a
      comparative study.
AB  - To compare the results of mammographic and US examinations in unilateral and
      bilateral breast cancers in routine clinical work, the files of all patients with
      825 preoperative mammograms and 525 preoperative US examinations operated on for
      primary breast cancer in the Oulu University Hospital from 1983 through 1993 were
      retrospectively reviewed. The only statistically significant difference noted in
      the mammographic findings was the false-negative rates in unilateral, bilateral
      and metachronous second breast cancers (6.8, 16.3 and 23.3 %, respectively). The
      differences were mainly due to the lower sensitivity of mammography in the
      detection of palpable bilateral breast cancers. The false-negative rate of US was
      also significantly higher in bilateral breast cancers (23 %) than in unilateral
      cancers (11 %), and significantly higher for nonpalpable than palpable cancers in
      both the bilateral and the unilateral groups. The mammographic failure rates and
      the difference between these two groups were most pronounced during the early
      study period, which underscores the importance of experience and dedicated
      imaging technique. The smaller tumour size at the time of diagnosis and probably
      the loss of the opposite breast for comparison have contributed to the higher
      false-negative rates in bilateral breast cancer.

PMID- 9569340
TI  - Invasive interval cancers in the Ostergotland Mammographic Screening Programme:
      radiological analysis.
AB  - The aim of this study was to find out by radiological analysis whether it is
      possible to prevent interval cancers in screening programmes without a
      concomitant increase in false positives. Re-scrutiny of all mammograms of 544
      interval cancers was implemented. Blinded re-scrutiny of screening mammograms of
      390 interval cancers mixed with other cases (prevalence of detectable cases 37 %)
      by two outside radiologists was also carried out. True interval cancers
      constituted 49 %, missed tumours 25 %, occult tumours 10 % and unclassifiable
      cases 16 %. There were no significant differences in survival between true
      interval cancers, overlooked or misinterpreted cancers, and mammographically
      occult cancers. In the blinded re-scrutiny both examiners reached a positive
      predictive value for malignancy of 67 %, and a sensitivity of 69 % and 81 %,
      respectively. In a screening programme such as this, it was estimated that 100
      400 additional women would have to be recalled from screening for further workup
      in order to detect each additional cancer which would otherwise emerge as an
      interval cancer. The occurrence of interval cancer increased with age and was
      influenced by the design of screening. The proportion of patients with potential
      iatrogenic delay in diagnosis (overlooked and misinterpreted cancers) was
      equivalent to figures from other studies. There were no significant differences
      in survival between the various categories of interval cancer. The study
      confirmed the association of criteria for referral for further investigation with
      the number of false positives. Efforts to reduce the number of interval cancers
      by lowering the threshold for recall are likely to be counterproductive.

PMID- 9569341
TI  - Mammographic demonstration of steatocystoma multiplex.
AB  - Steatocystoma multiplex (SM) is a rare inherited cutaneous disorder characterised
      by multiple subcutaneous oil cysts. We present the radiological features of this
      uncommon condition in a case report. Numerous lucent, well-circumscribed, smooth
      walled nodules appeared in both breasts at mammography. Many lipid-containing
      intradermal cysts of different sizes were also observed at sonography, scattered
      over both breasts, axillae, sternal region and abdomen. SM was suspected and no
      further evaluations were made.

PMID- 9569342
TI  - Amplitude-coded colour Doppler sonography: physical principles and technique.
AB  - The purpose of this review is to help in understanding the principles of a new
      ultrasound Doppler technique called amplitude-coded colour Doppler (power) mode.
      All pertinent information available in the literature on the physical principles
      of this technique has been revised in order to give a detailed survey. The main
      components and the key characteristics of this mode are discussed together with
      illustrative examples. In addition, work-in-progress developments and other
      future aspects of US imaging in combination with this technique are discussed.

PMID- 9569343
TI  - Three-dimensional computed tomography of the reconstructed lower urinary tract:
      technique and findings.
AB  - The aim of this pilot study in 54 patients was to improve the visualization of
      the anatomy and postoperative changes in the pelvic topography after bilateral
      ureteroileal urethrostomy, using surface rendering of electron beam CT (EBCT)
      data for the 3D display. Fifty-four patients (39 men and 15 women) were scanned
      with an EBCT unit between 3 and 110 months after performing orthotopic
      ureteroileal urethrostomy ("Hemi-Kock") or ureteroileal rectosigmoidostomy.
      Various parameters and spatial viewing points were used in the 3D reconstruction,
      which was performed interactively on external workstations with commercially
      available software. The anti-reflux nipple was visualized as a distinct structure
      in all patients. In 8 patients with an interval of more than 12 months between
      surgery and CT, the pouch had developed an ovoid shape almost indistinguishable
      from the original bladder. The segmented data sets were partly animated to
      display the anatomy as virtual endoscopy. Three-dimensional depiction and virtual
      endoscopy of the neobladder using EBCT are a new way of imaging the postoperative
      anatomy. Its clinical efficacy in the diagnosis of inconclusive postoperative
      morbidity, especially voiding problems, and planning of necessary therapy have to
      be the subject of further evaluation.

PMID- 9569345
TI  - Imaging findings of sternal abnormalities.

PMID- 9569344
TI  - Would thyroid and breast shielding be beneficial in CT of the head?
AB  - Contrary to common perception, the advent of third- and fourth-generation
      scanners has lead to a significant increase in radiation dose to the patient per
      computed tomography (CT) head scan. With that in mind, a pilot study was designed
      with the objective of assessing the effectiveness of a dental-style protective
      bib in reducing the dose to the radiosensitive organs of the neck and thorax.
      Radiation doses over the thyroid gland and breast were measured with
      thermoluminenscent dosemeters and an ionization chamber respectively in 110
      patients undergoing routine head scans. Half the patients wore the protective bib
      and collar. With lead protection, the thyroid measurements were reduced by an
      average of 45 % and the breast measurements by an average of 76 %. Similar
      results were seen in phantom measurements.

PMID- 9569346
TI  - Radiology in Ukraine.

PMID- 9569348
TI  - Development of polyembryonic insects: a major departure from typical insect
      embryogenesis.
AB  - The parasitic wasp Copidosoma floridanum represents the most extreme form of
      polyembryonic development known, forming up to 2000 embryos from a single egg. To
      understand the mechanisms of embryonic patterning in polyembryonic wasps and the
      evolutionary changes that led to this form of development we have analyzed
      embryonic development at the cellular level using confocal and scanning electron
      microscopy. C. floridanum embryogenesis can be divided into three phases: (1)
      early cleavage that leads to formation of a primary morula, (2) a proliferative
      phase that involves partitioning of embryonic cells into thousands of morulae,
      and (3) morphogenesis whereby individual embryos develop into larvae. This
      developmental program represents a major departure from typical insect
      embryogenesis, and we describe several features of morphogenesis unusual for
      insects. The early development of polyembryonic wasps, which likely evolved in
      association with a shift in life history to endoparasitism, shows several
      analogies with mammalian embryogenesis, including early separation of
      extraembryonic and embryonic cell lineages, formation of a morula and embryonic
      compaction. However, the late morphogenesis of polyembryonic wasps proceeds in a
      fashion conserved in all insects. Collectively, this suggests a lack of
      developmental constraints in early development, but a strong conservation of the
      phylotypic stage.

PMID- 9569347
TI  - Fin duplications and deletions induced by disruption of retinoic acid signaling.
AB  - Retinoic acid (RA), a derivative of vitamin A, plays a critical role as a
      signaling molecule in axial patterning of vertebrates. Here we report that RA
      exposure of zebrafish (Danio rerio) and mummichog (Fundulus heteroclitus) embryos
      during gastrulation results in homeotic duplications of the pectoral fins in up
      to 94% of fish. We have observed three to four pairs of fins in an individual
      fish. Although some duplications are partial, many represent complete axial
      duplications of the pectoral girdle and fin and include coracoscapulae, proximal
      radials, and dermal fin elements. Fin duplications are observed only at a defined
      dose of RA. Inhibition of RA synthesis by exposure to citral during a narrow
      developmental window leads to fish which lack pectoral fins but can be rescued by
      addition of exogenous RA, suggesting that RA signaling is critical to fin
      specification during early development. The ability to consistently induce
      multiple fins in a large number of vertebrate embryos should contribute to the
      understanding of genetic regulation of the normal positioning of limbs during
      embryogenesis.

PMID- 9569349
TI  - Evolutionary changes in sites and timing of actin gene expression in embryos of
      the direct- and indirect-developing sea urchins, Heliocidaris erythrogramma and
      H. tuberculata.
AB  - We describe an evolutionary comparison of expression of the actin gene families
      of two congeneric sea urchins. Heliocidaris tuberculata develops indirectly via a
      planktonic feeding pluteus that forms a juvenile rudiment after a long period of
      larval development. H. erythrogramma is a direct developer that initiates
      formation of a juvenile rudiment immediately following gastrulation. The
      developmental expression of each actin isoform of both species was determined by
      in situ hybridization. The observed expression patterns are compared with known
      expression patterns in a related indirect-developing sea urchin,
      Strongylocentrotus purpuratus. Comparisons reveal unexpected patterns of
      conserved and divergent expression. Cytoplasmic actin, CyIII, is expressed in the
      aboral ectoderm cells of the indirect developers, but is an unexpressed
      pseudogene in H. erythrogramma, which lacks aboral ectoderm. This change is
      correlated with developmental mode. Two CyII actins are expressed in S.
      purpuratus, and one in H. erythrogramma, but no CyII is expressed in H.
      tuberculata despite its great developmental similarity to S. purpuratus. CyI
      expression differs slightly between Heliocidaris and Strongylocentrotus with more
      ectodermal expression in Heliocidaris. Evolutionary changes in actin gene
      expression reflect both evolution of developmental mode as well as a surprising
      flexibility in gene expression within a developmental mode.

PMID- 9569350
TI  - Characterization of the zebrafish tbx16 gene and evolution of the vertebrate T
      box family.
AB  - We report on a new zebrafish T-box-containing gene, tbx16. It encodes a message
      that is first detected throughout the blastoderm soon after the initiation of
      zygotic gene expression. Following gastrulation, expression becomes restricted to
      paraxial mesoderm and later primarily to the developing tail bud. To gain an
      evolutionary prospective on the potential function of this gene, we have analyzed
      its phylogenetic relationships to known T-box genes from other species. Zebrafish
      tbx16 is likely orthologous to the chicken Tbx6L and Xenopus
      Xombi/Antipodean/Brat/VegT genes. Our analysis also shows that zebrafish tbx6 and
      mouse Tbx6 genes are paralogous to zebrafish tbx16. We present evidence which
      argues, that despite the same name and similar expression, zebrafish tbx6 and
      mouse Tbx6 genes are not orthologous to each other but instead represent
      relatively distant paralogs. The expression patterns of all genes are discussed
      in the light of their evolutionary relationships.

PMID- 9569351
TI  - Characterization and developmental expression of AmphiNk2-2, an NK2 class
      homeobox gene from Amphioxus. (Phylum Chordata; Subphylum Cephalochordata).
AB  - The genome of amphioxus includes AmphiNk2-2, the first gene of the NK2 homeobox
      class to be demonstrated in any invertebrate deuterostome. AmphiNk2-2 encodes a
      protein with a TN domain, homeodomain, and NK2-specific domain; on the basis of
      amino acid identities in these conserved regions, AmphiNk2-2 is a homolog of
      Drosophila vnd and vertebrate Nkx2-2. During amphioxus development, expression of
      Amph- iNk2-2 is first detected ventrally in the endoderm of late gastrulae. In
      neurulae, endodermal expression divides into three domains (the pharynx, midgut,
      and hindgut), and neural expression commences in two longitudinal bands of cells
      in the anterior neural tube. These neural tube cells occupy a ventrolateral
      position on either side of the cerebral vesicle (the probable homolog of the
      vertebrate diencephalic forebrain). The dynamic expression patterns of AmphiNkx2
      2 suggest successive roles, first in regionalizing the endoderm and nervous
      system and later during differentiation of specific cell types in the gut
      (possibly peptide endocrine cells) and brain (possibly including axon outgrowth
      and guidance).

PMID- 9569352
TI  - Apoptosis of nurse cells at the late stages of oogenesis of Drosophila
      melanogaster.
AB  - In Drosophila a remarkable feature of oogenesis is the regression of the nurse
      cells after dumping their cytoplasmic contents into the oocyte. We have studied
      the nature of this process at the late stages of egg chamber development. In egg
      chambers DAPI staining shows highly condensed chromatin from stage 12 and TUNEL
      labelling shows DNA fragmentation up to stage 14. Gel electrophoresis of the end
      labelled DNA, extracted from isolated egg chambers at the same stages of
      development, shows a ladder typical of apoptotic nuclei. This provides evidence
      that, during Drosophila oogenesis, the nurse cells undergo apoptosis. Apoptotic
      nuclei have also been detected in dumping-defective egg chambers, indicating that
      the cytoplasmic depletion of nurse cells is concurrent with but apparently not
      the cause of the process.

PMID- 9569353
TI  - The PBC domain contains a MEINOX domain: coevolution of Hox and TALE homeobox
      genes?
AB  - A recent survey of TALE superclass homeobox genes revealed a new domain upstream
      of the homeodomain that is conserved between the plant KNOX genes and the animal
      MEIS genes. At the same time, another paper identified the Drosophila gene
      homothorax (hth) as a homologue of the vertebrate MEIS genes, which prompted a
      reexamination of the sequences of the MEIS, KNOX (collectively named MEINOX) and
      PBC domains. Similarity of the complete MEINOX domain was found within the PBC
      domain. This suggests that the PBC class genes were also derived from the ancient
      MEINOX genes. Recently, it has been shown that the MEIS genes can interact with
      the Abd-B genes, whilst previous results have shown that the PBC genes interact
      with anterior Hox genes. This leads to the hypothesis that the duplication of an
      ancestral MEINOX gene into the PBC and MEIS genes happened at a point in time
      when the first two Hox cluster genes, an anterior one and a posterior one,
      emerged, and that subsequently these gene classes coevolved.

PMID- 9569354
TI  - Endoscopic retrograde cholangiopancreatography (ERCP) and the surgeon.
      Interventional endoscopy in the management of complex hepatobiliary and
      pancreatic disease.

PMID- 9569355
TI  - Diagnostic laparoscopy in mesenteric ischemia.

PMID- 9569356
TI  - Endoscopic sphincterotomy for the treatment of gallstone pancreatitis during
      pregnancy.
AB  - BACKGROUND: Gallstones are the most common cause of acute pancreatitis during
      pregnancy. Without intervention, gallstone pancreatitis during pregnancy is
      associated with an antepartum recurrence rate of 70%, which exposes the mother
      and fetus to an increased risk of morbidity and mortality. A safe, effective
      means to prevent recurrent gallstone pancreatitis during pregnancy is desirable.
      METHODS: Since 1991, we have managed gallstone pancreatitis in three pregnant
      patients with endoscopic retrograde cholangiogram (ERC), followed by
      spincterotomy, despite the absence of common bile duct stones. RESULTS: All
      patients were judged to have mild pancreatitis by modified Ranson criteria and
      the Multiorgan System Failure criteria. During cholangiogram, fetal shielding was
      employed and fluoroscopy times ranged from 36 s to 7.2 min. One patient
      experienced postprocedure pancreatitis of 48-h duration. None of the patients
      experienced further episodes of pancreatitis and none underwent predelivery
      cholecystectomy. CONCLUSIONS: In pregnancy-associated gallstone pancreatitis,
      endoscopic sphincterotomy prevents recurrence of pancreatitis and the need for
      cholecystectomy during gestation. We believe endoscopic sphincterotomy represents
      a promising management alternative for gallstone pancreatitis during pregnancy.
      Further investigation is warranted.

PMID- 9569357
TI  - Selective role for endoscopic retrograde cholangiopancreatography in abdominal
      trauma.
AB  - BACKGROUND: Emergency endsocopic retrograde cholangiopancreatography (ERCP) is
      rarely indicated in trauma patients; however, in cases of suspected pancreatic or
      bile duct injury or bile leak, it may be useful. The purpose of this paper is to
      review our ERCP experience in trauma patients. Our Level I Trauma Center admits
      1800 patients annually. METHODS: Since January 1991, we have performed ERCP in 12
      trauma patients, nine after blunt injury and three after penetrating injury.
      RESULTS: ERCP was used as a diagnostic tool to evaluate the pancreatic duct in
      six stable patients with equivocal CT scans and unexplained abdominal pain,
      fever, and an elevated amylase or a peripancreatic pseudocyst. Based on their
      ERCP findings-one intact pancreatic duct, one transected duct, and four
      pseudocysts-five of the six patients had operations. We performed ERCP in six
      patients for persistent bile leaks (five cases) or jaundice (one case). The
      findings were one case of bilemia (intrahepatic biliovenous fistula), one case of
      common bile duct disruption, and four cases of persistent bile leaks from the
      liver after liver injuries. Endobiliary stents placed in five patients
      successfully stopped the four bile leaks and closed the biliovenous fistula. The
      one case of ductal disruption required an open choledochojejunostomy. The only
      ERCP complication was an episode of cholangitis treated with antibiotics. The
      earliest ERCP was 3 days after injury, and most were performed within 2 months.
      CONCLUSIONS: ERCP is a helpful procedure for diagnosing biliary and pancreatic
      duct injury in a select group of trauma patients who do not have obvious
      indications for exploration. In addition, ERCP techniques are also effective for
      treating most bile leaks.

PMID- 9569358
TI  - Endoscopic electrohydraulic lithotripsy in the management of pancreatobiliary
      lithiasis.
AB  - BACKGROUND: Clinical evaluation of intraoperative endoscopy with electrohydraulic
      lithotripsy (EHL) in the management of 13 patients with pancreatobiliary
      lithiasis was undertaken. METHODS: Ten patients with chronic pancreatitis with
      intraductal lithiasis in the head and three with biliary lithiasis (one
      choledochal, one cystic, one right intrahepatic) underwent intraoperative
      endoscopy with EHL. Shock waves were applied by visual contact with a 3-Fr gauge
      EHL probe until all stones were fragmented and irrigated free. All pancreatitis
      patients had failed ERCP attempts to stent their pancreatic ducts secondary to
      ductal lithiasis. Patients with pancreatic stones underwent lateral
      pancreatojejunostomy. Biliary stone patients underwent laparoscopic
      cholecystectomy with common duct exploration (two cases) and open cholecystectomy
      with choledochoduodenostomy (one case). RESULTS: Intraductal stone eradication
      was successful in all patients. Transampullary visualization of the duodenum was
      achieved in eight cases. Average EHL time was 65 min. There was no evidence of
      postoperative pancreatitis, cholangitis, or retained common duct stones.
      CONCLUSION: Intraoperative pancreatobiliary endoscopy with EHL is safe and
      effective in the eradication of pancreatic and bile duct stones. This novel
      technique represents a valuable adjunct in the management of chronic
      fibrocalcific pancreatitis with ductal lithiasis in the head region and in the
      open and laparoscopic management of intra- and extrahepatic bile duct stones.

PMID- 9569359
TI  - Minimal increase in gut-mucosal interleukin-6 during laparoscopy.
AB  - BACKGROUND: The gut clearly plays a significant role in postoperative recovery.
      Other investigators have shown an increase in gut-mucosal cytokines in septicemia
      and burn models. We tested the effects of laparotomy and laparoscopy on gut
      mucosal IL-6 production. METHODS: A/J mice were randomized to three groups:
      control, laparotomy plus bowel manipulation (OBM), and laparoscopy plus bowel
      manipulation (LBM). Serum and gut-mucosal samples obtained at 4 and 8 h after
      surgery were analyzed for IL-6. RESULTS: We found that OBM is associated with
      increased serum and gut-mucosal IL-6 at both 4 and 8 h after surgery. In
      contrast, LBM showed a blunted response in serum IL-6 and no change in gut
      mucosal IL-6 at both time intervals. CONCLUSIONS: We conclude that laparoscopy
      minimizes trauma to the peritoneal environment, thereby decreasing the gut's
      inflammatory response to operation. This differential response of the gut may
      partially explain the preservation of gut function following laparoscopy.

PMID- 9569360
TI  - Laparoscopic vs conventional bowel resection in the rat. Earlier restoration of
      serum insulin-like growth factor 1 levels.
AB  - BACKGROUND: The role of laparoscopic surgery in the treatment of colorectal
      disease is still controversial. To assess the metabolic consequences of
      laparoscopic and open bowel surgery, we studied serum levels of insulin-like
      growth factor 1 (IGF-1), an anabolic and mitogeneic peptide, in rats. MATERIALS
      AND METHODS: In experiment 1, the serum IGF-1 levels of 10 rats undergoing
      laparoscopic small bowel resections (group I) and 10 rats undergoing conventional
      small bowel resections (group II) were determined before surgery and on days 1,
      2, and 7. Experiment 2 compared five rats that had CO2 pneumoperitoneum (group
      III), five rats that underwent laparotomy (group IV), and five rats that received
      anesthesia only (group V). Differences in IGF-1 levels were tested with analysis
      of covariance. RESULTS: In experiment 1, preoperative IGF-1 levels were similar
      in groups I and II (87.9 +/- 6.1 nmol/L versus 90.5 +/- 8.1 nmol/L). One day
      after surgery IGF-1 was 54.6 +/- 10.5 in group I versus 41.6 +/- 8.3 in group II
      (p = 0.006). Two days after surgery, IGF-1 was 79.4 +/- 9.2 in group I versus
      59.0 +/- 10.5 in group II (p < 0.001). Seven days after both types of surgery,
      IGF-1 levels had returned to almost normal levels. In experiment 2, no
      significant differences were found between the rats with CO2 pneumoperitoneum
      (group III) and those with laparotomy only (group IV). Rats that had anaesthesia
      only showed a significant decrease in IGF-1 levels between days 0 and 1 (p <
      0.018). CONCLUSION: Our study indicates that laparoscopic bowel surgery is
      associated with a better postoperative anabolic state (i.e., less catabolism)
      than conventional surgery. This finding reflects a potential benefit of
      laparoscopy in bowel surgery.

PMID- 9569361
TI  - Hemodynamic and metabolic effects of CO2 pneumoperitoneum in an experimental
      model of hemorrhagic shock due to retroperitoneal hematoma.
AB  - BACKGROUND: Diagnostic laparoscopy has been used in abdominal trauma patients,
      although its role is not well defined. The safety of laparoscopic evaluation in
      trauma patients with severe intraabdominal hemorrhage has not yet been analyzed.
      The purpose of this study is to evaluate the hemodynamic and metabolic effects of
      CO2 pneumoperitoneum (COI) in hemorrhaged animals through a retroperitoneal
      hematoma (RH). METHODS: Twenty-two 15-20-kg mongrel dogs were monitored for
      systemic and pulmonary hemodynamics, inferior vena cava pressure, and arterial
      blood gases. After 1 h of baseline, all animals were submitted to a RH. After 45
      min the dogs were randomized into two groups. Control (CTR): dogs were submitted
      only to a RH; pneumoperitoneum (PN): dogs were submitted to a RH and 45 min later
      they were insufflated to an intraabdominal pressure of 10 mmHg with medical-grade
      CO2 gas for 30 min. Echocardiography was performed, only in PN animals, at
      baseline, 45 and 60 min after RH. RESULTS: RH induced a shock condition with low,
      sustained levels of arterial pressure, cardiac index, left ventricular stroke
      index, base excess, and oxygen delivery which were further depressed following
      COI. Three deaths occurred in the PN group, all of them toward the end of COI.
      During COI, hypercapnia was observed in one animal. COI did not impair systolic
      function or ejection fraction. CONCLUSIONS: COI with an IAP of 10 mmHg may be
      deleterious in animals with hemorrhagic shock due to an intraabdominal lesion.
      These findings could be clinically significant in abdominal trauma patients.

PMID- 9569362
TI  - Esophageal and lower esophageal sphincter pressure profiles 6 and 24 months after
      laparoscopic fundoplication and their association with postoperative dysphagia.
AB  - BACKGROUND: It has been suggested that antireflux surgery may cause an
      improvement in esophageal motor function (EMF) and lead to reduced postoperative
      dysphagia. METHODS: We evaluated the changes in dysphagia symptom scores and
      esophageal and lower esophageal sphincter (LES) pressures in patients before (n =
      381), at 6 months (n = 260), and at 24 months (n = 97) after laparoscopic
      fundoplication. RESULTS: There was a significant increase in LES basal and nadir
      pressure following surgery in all patients and an improvement in EMF only in
      patients with poor preoperative esophageal motor function. A total of 76% of the
      patients reported no dysphagia or an improved dysphagia score 6 and 24 months
      after surgery. This improvement was more marked in patients with poor EMF. An
      improvement in EMF did not correlate with the improvement in dysphagia score
      reported by other patients. Patients with increased dysphagia scores 2 years
      after surgery had significantly higher LES basal and nadir pressures as compared
      to other patients. CONCLUSIONS: Laparoscopic Nissen fundoplication is associated
      with an overall reduction in dysphagia scores and leads to an improvement in
      esophageal motor function in patients with poor preoperative esophageal motility.
      Tightness and inadequate relaxation of the wrap during swallowing may be a
      determinant of long-term dysphagia.

PMID- 9569363
TI  - Hepatic and portal vein blood flow during carbon dioxide pneumoperitoneum for
      laparoscopic hepatectomy.
AB  - BACKGROUND: Laparoscopy under carbon dioxide (CO2) pneumoperitoneum has many
      advantages. However, the risks of CO2 pneumoperitoneum during laparoscopic
      hepatectomy (LH) have not been defined. METHODS: The hemodynamics of the hepatic
      vein were examined during CO2 pneumoperitoneum both pre- and posthepatectomy in
      eight pigs. Portal blood flow was measured with Doppler ultrasound during
      laparoscopic cholecystectomy in 10 human patients. RESULTS: Experimentally,
      elevated intraabdominal pressure (IAP) with CO2 insufflation produced significant
      increases in CO2 partial pressure and echogenicity of the hepatic vein in the
      posthepatectomy group. Clinically, elevated IAP caused significant narrowing of
      the portal vein and significant decreases in portal blood velocity. The mean
      portal flow was significantly decreased with elevation of IAP >10 mmHg.
      CONCLUSIONS: LH with CO2 pneumoperitoneum may lead to embolism caused by CO2
      bubbling through the hepatic vein. Elevated IAP may cause a decrease in hepatic
      blood flow and induce severe liver damage, especially in patients with poor liver
      function. Gasless laparoscopy using abdominal wall lifting should be employed in
      LH to avoid the risks of CO2 embolism and liver damage.

PMID- 9569364
TI  - Effect of carbon dioxide pneumoperitoneum on bacteremia and severity of
      peritonitis in an experimental model.
AB  - BACKGROUND: Laparoscopy is increasingly used in conditions complicated by
      peritonitis. A theoretical concern is that carbon dioxide pneumoperitoneum may
      increase bacteremia. METHOD: In 60 rats peritonitis was induced by cecostomy.
      Animals were randomly allocated to pneumoperitoneum (PP) and control groups.
      Blood cultures and intraabdominal swabs were assessed. A peritonitis severity
      score (PSS) was computed based on histology from peritoneal biopsy. RESULTS: One
      hour after cecostomy neither in abdominal swabs nor in blood samples bacteria
      were reproduced in PP and control groups. Three hours after cecostomy the
      frequency of positive blood cultures was 80% and 20% in PP and control groups,
      respectively (p < 0.0001). Six hours after cecostomy the frequency of positive
      blood cultures was 100% in each group (p > 0.05). One hour after cecostomy the
      mean peritoneal severity score was significantly higher in the PP group than in
      the control group, but there was not any significant difference between groups 3
      and 6 h after cecostomy. The mean peritoneal severity scores were found to be
      significantly increased with time when the PP groups compared with each other.
      CONCLUSION: In rats, pneumoperitoneum can't cause a more severe peritonitis but
      it does induce an increase in the rate of bacteremia within the early 6-h period
      of peritonitis.

PMID- 9569365
TI  - An in vitro model fails to demonstrate aerosolization of tumor cells.
AB  - BACKGROUND: We investigated the ability of pressurized CO2 gas to aerosolize B16
      melanoma (B16) tumor cells in an in vitro model. METHODS: The experimental
      apparatus consisted of an 18.9-L plastic cylindrical vessel and a compliant latex
      pouch was attached to the top. Two 5-mm ports penetrated the vessel; insufflation
      and desufflation were carried out through them. A culture dish containing 20
      million B16 cells in liquid culture media was placed at the base within the
      container. In the first experiment, the vessel was insufflated with CO2 gas to a
      static pressure of 15 or 30 mm Hg with the outflow port closed. After 10 min, the
      outflow port was opened and the gas was desufflated through a collecting device
      containing sterile culture medium. In a second experiment, a continuous flow of
      CO2 through the vessel was maintained after a pressure of 15 or 30 mm Hg was
      established. A total of 10 L CO2 was cycled through the vessel. In both
      experiments, 24 determinations were carried out at each pressure. Each
      experimental culture dish was microscopically scanned for 2 weeks for the
      presence of tumor cells. The third and fourth experiments tested for the presence
      of aerosolized nonviable tumor cells in the expelled gas. Using the model
      described above, after 10 mins of 30 mm Hg static pressure, the CO2 gas was
      expelled directly onto a glass slide and cytofixed. Alternately, after 10 mins at
      30 mm Hg static pressure, the gas was expelled through a saline-filled Soluset
      (Abbott Laboratories), centrifuged, and the residue cytofixed onto a glass slide.
      Each of the five slides per experiment were examined microscopically for the
      presence of cells. RESULTS: In the first and second experiments, no cells or
      growth were observed in any of the 96 experimental dishes. In experiments three
      and four, no cells were detected on any of the slides. CONCLUSIONS: It was not
      possible with this model to aerosolize tumor cells in a pressurized CO2
      environment. Our results suggest that aerosolization of tumor cells is not the
      mechanism of port site recurrences after laparoscopic surgery for malignant
      disease.

PMID- 9569366
TI  - Comparison of four minimally invasive methods of laparoscopic vagotomy in a
      porcine model.
AB  - BACKGROUND: An experimental study in a porcine model was undertaken to evaluate
      the currently available techniques of laparoscopic vagotomy. METHODS: Four groups
      of pigs were studied. Under general anesthesia, the animals were submitted to
      either bilateral vagotomy, bilateral highly selective vagotomy, posterior truncal
      vagotomy with anterior highly selective vagotomy, or Taylor's procedure. Gastric
      acid secretion and intestinal motility were evaluated before and after the
      surgical procedure. The feasibility of the four different techniques was assessed
      by means of a personal difficulty score. RESULTS: All four procedures produced
      significant acid secretory reduction. Multivariate analysis showed that the
      factor most affecting the outcome was the difficulty score. CONCLUSIONS: Taylor's
      procedure was the easiest and safest technique. It also produced the best
      functional results for secretion and motility.

PMID- 9569367
TI  - Video-assisted interventional bronchoscopy. The Hong Kong experience.
AB  - BACKGROUND: Major airway obstruction due to benign or malignant etiology is not
      uncommon and is always distressing. Intraluminal stenting has been shown to be a
      safe and effective approach for symptomatic relief in selected patients based on
      the European and North American experience. METHODS: We reviewed our experience
      in Hong Kong on airway stenting over a 19-month period. RESULTS: From February
      1994 to August 1995, 33 silicone stents (Dumon stent, Cometh, Marseille, France)
      were placed in 23 patients (20 males, three females with mean age 61.4 years,
      range from 26 to 81). Eighteen stents were placed in the trachea, nine in the
      left main stem, five in the right main stem, and one Y-stent over the carina.
      Twelve patients had esophageal carcinoma involving the airway, seven had
      bronchial carcinoma, one had metastatic carcinoma, and three had benign
      strictures (of which two were due to tuberculosis). There was no procedural
      related mortality. Stent migration occurred in four patients (17%) and required
      stent change. Symptoms were improved in all patients as documented by the visual
      analogue scale. CONCLUSION: Our experience represents the "stentable" diseases
      seen in Hong Kong, where carcinoma of the esophagus (and tuberculosis) remains
      prevalent. We conclude that intraluminal stenting remains a safe and effective
      approach in selected patients with critical airway stenosis. Complications,
      however, do exist and should be realized by the operator, the patients, and their
      families.

PMID- 9569368
TI  - Unusual intraoperative complication in laparoscopic sigmoidectomy.
AB  - The authors report a case of complete rotation of the left colon after
      laparoscopic sigmoidectomy. Such an uncommon complication in open colectomies has
      not been previously described with the laparoscopic approach. During the
      performance of laparoscopic-assisted colectomies the proximal segment of the
      colon can be rotated when removing the specimen through a small incision.
      Therefore we recommend inspecting the position of the colon before the stapler is
      fired.

PMID- 9569369
TI  - Jaundice following laparoscopic cholecystectomy. An unusual complication of
      spilled stones.
AB  - We report the first case of obstructive cholangitis after laparoscopic
      cholecystectomy, related to intraperitoneal retained gallstones.

PMID- 9569370
TI  - Anaphylactic shock complicating laparoscopic treatment of hydatid cysts of the
      liver.
AB  - Hydatid cysts of the liver have been treated surgically for many years by several
      surgical techniques including evacuation, marsupialization, and filling the cyst
      with saline after evacuation of the endocyst. We have previously reported
      laparoscopic treatment of hydatid cysts using the same hydatid asepsis and
      surgical techniques as in open surgery, with comparable results. Spillage of
      hydatid fluid during open surgery has been shown to result in serious
      anaphylactic reaction. The present report describes the first case report of such
      a reaction during laparoscopic treatment of hydatid cyst of the liver.

PMID- 9569371
TI  - Late rejection of the mesh after laparoscopic hernia repair.
AB  - We report the first case of late rejection of a mesh after laparoscopic hernia
      repair. It occurred in a 48-year-old man who had had a laparoscopic hernia repair
      by transabdominal preperitoneal approach 3 years earlier. The most characteristic
      finding was the slow development of a firm mass in the right groin, without pain
      or fistula. At admission 3 months later, US and CT scans demonstrated a necrotic
      mass extending into both iliac fossa. The mass was approached through a midline
      incision. Pus was taken for microscopic examination (negative), and the mesh was
      removed, along with several staples. Ultramicroscopic examination of the mesh
      showed breakdown of the fibers, collagen reduction, and no chronic inflammatory
      cells. No infectious cause of inflammation was identified.

PMID- 9569372
TI  - Surgical technology and the ergonomics of laparoscopic instruments.
AB  - Laparoscopic surgery provides patients with less painful surgery and a more rapid
      recovery, while requiring that surgeons work harder and in a more remote manner
      from the operating field. Cost-containment pressures on surgeons demand efficient
      surgery, whereas the increased technological complexity and sometimes poorly
      adapted equipment have led to increased complaints of surgeon fatigue and
      discomfort during laparoscopic surgery. There is, therefore, a need to evaluate
      the ergonomic integration and suitability of the laparoscopic operating room
      environment to address the issues of efficiency, safety, and comfort for the
      operating team. This approach is particularly important in the design of
      laparoscopic surgical instruments. A review of the literature on the biomechanics
      of laparoscopic surgical instrument use was combined with data from the Society
      of American Gastrointestinal and Endoscopic Surgeons (SAGES) Ergonomics
      Questionnaire and demonstration station. Laparoscopic instruments suffer from
      ergonomically inadequate handle designs and inefficient handle to tip force
      transmission, which lead to surgeon fatigue, discomfort, and hand paresthesias.
      Improvements in the design of laparoscopic instruments are needed to decrease the
      work and discomfort of tissue manipulation during video-endoscopic surgery.

PMID- 9569373
TI  - Endoscopic in situ bypass. A gentler dissection.
AB  - We believe that this is the first report of a gasless endoscopic in situ bypass
      technique. We have pursued this minimally invasive procedure with the hope that
      wound complications and operative time might be improved without compromising
      graft patency. Having demonstrated the feasibility of minimally invasive lower
      extremity bypass we would urge further study to assess the safety and efficacy of
      this promising approach.

PMID- 9569374
TI  - Minimally invasive surgery for axillary dissection. Cadaveric feasibility study.
AB  - Axillary dissection is the major cause of morbidity in breast cancer and primary
      cutaneous melanoma of the extremity. In the present study, we examine the
      potential benefits and advantages of endoscopic axillary lymph node dissection
      over conventional surgery. Twenty endoscopic axillary dissections and 10 lymph
      node samplings were performed in 10 cadavers (four male, six female). A
      preperitoneal distention balloon (PDB) system was used to dissect the axilla. In
      four of the cadavers, the procedure was followed by open surgery. The axillary
      contents were examined for lymphatic tissue by a pathologist. The endoscopic
      technique offered easy access to the axilla and clear visualization of the
      axillary vein, as well as the long thoracic and thoracodorsal nerves. Results
      were comparable to those achieved with the classic surgical dissection. Endoscopy
      is feasible for axillary lymph node dissection and sampling in cases of breast
      cancer and primary cutaneous melanoma of the extremity. Further studies in
      patients are needed to reach definitive conclusions.

PMID- 9569375
TI  - Endoscopic treatment of choledochocele.

PMID- 9569376
TI  - The author replies 

PMID- 9569377
TI  - Endoluminal surgery.

PMID- 9569378
TI  - The author replies 

PMID- 9569379
TI  - 6th World Congress of Endoscopic Surgery (IFSES). 6th International Congress of
      the European Association of Endoscopic Surgery (E.A.E.S.) 1st World Expo of
      Surgical Techniques. Rome, Italy, 31 May-6 June 1998. Abstracts.

PMID- 9569381
TI  - 6th world congress of endoscopic surgery (IFSES)6th international congress of the
      european association of endoscopic surgery (E.A.E.S. )1st world expo of surgical
      TechnologiesRome, italy, 31 may-6 june 1998Poster presentations 

PMID- 9569380
TI  - 6th world congress of endoscopic surgery (IFSES)6th international congress of the
      european association of endoscopic surgery (E.A.E.S. )1st world expo of surgical
      TechnologiesRome, italy, 31 may-6 june 1998Oral presentations 

PMID- 9569382
TI  - 6th world congress of endoscopic surgery (IFSES)6th international congress of the
      european association of endoscopic surgery (E.A.E.S. )1st world expo of surgical
      TechnologiesRome, italy, 31 may-6 june 1998Video presentations 

PMID- 9569383
TI  - News and notices 

PMID- 9569384
TI  - Smoking in public should be restricted.

PMID- 9569386
TI  - Teen pregnancies rise in England and Wales.

PMID- 9569385
TI  - Secrecy still surrounds contraception in Ireland.

PMID- 9569388
TI  - Call for national body to ensure blood transfusion safety.

PMID- 9569389
TI  - Irish face flood of compensation claims.

PMID- 9569390
TI  - Catalonia tries to tackle growing waiting lists.

PMID- 9569391
TI  - Turnaround in cancer trends seen in the US.

PMID- 9569392
TI  - Anaesthesiologists in battle against nurse anaesthetists in the US.

PMID- 9569393
TI  - Commentary: safety of participants in non-therapeutic research must be ensured.

PMID- 9569394
TI  - Commentary: ethical approval of study was warranted.

PMID- 9569395
TI  - Lowering blood homocysteine with folic acid based supplements: meta-analysis of
      randomised trials. Homocysteine Lowering Trialists' Collaboration.
AB  - OBJECTIVE: To determine the size of reduction in homocysteine concentrations
      produced by dietary supplementation with folic acid and with vitamins B-12 or B
      6. DESIGN: Meta-analysis of randomised controlled trials that assessed the
      effects of folic acid based supplements on blood homocysteine concentrations.
      Multivariate regression analysis was used to determine the effects on
      homocysteine concentrations of different doses of folic acid and of the addition
      of vitamin B-12 or B-6. SUBJECTS: Individual data on 1114 people included in 12
      trials. FINDINGS: The proportional and absolute reductions in blood homocysteine
      produced by folic acid supplements were greater at higher pretreatment blood
      homocysteine concentrations (P < 0.001) and at lower pretreatment blood folate
      concentrations (P < 0.001). After standardisation to pretreatment blood
      concentrations of homocysteine of 12 mumol/l and of folate of 12 nmol/l
      (approximate average concentrations for Western populations), dietary folic acid
      reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to
      28%; P < 0.001), with similar effects in the range of 0.5-5 mg folic acid daily.
      Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction
      in blood homocysteine. Vitamin B-6 (mean 16.5 mg daily) did not have a
      significant additional effect. CONCLUSIONS: Typically in Western populations,
      daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12
      would be expected to reduce blood homocysteine concentrations by about a quarter
      to a third (for example, from about 12 mumol/l to 8-9 mumol/l). Large scale
      randomised trials of such regimens in high risk populations are now needed to
      determine whether lowering blood homocysteine concentrations reduces the risk of
      vascular disease.

PMID- 9569396
TI  - Respect for privacy and the case of Mr K.

PMID- 9569398
TI  - Fast track admission for children with sickle cell crises. Jamaican sickle cell
      clinics offer an alternative to admission.

PMID- 9569397
TI  - Fast track admission for children with sickle cell crises. Opiates other than
      pethidine are better.

PMID- 9569399
TI  - Management of sickle cell disease. Management would improve if doctors listened
      more to patients.

PMID- 9569400
TI  - Management of sickle cell disease. Hearing loss may occur after sickle cell
      crises, especially in children.

PMID- 9569401
TI  - Management of sickle cell disease. Contraception with medroxyprogesterone may be
      beneficial.

PMID- 9569402
TI  - Future of preschool vision screening. Conclusions for or against services are
      invalid without appropriate research evidence.

PMID- 9569403
TI  - Future of preschool vision screening. Cost effectiveness of screening for
      amblyopia is a public health issue.

PMID- 9569404
TI  - Use of lasers can cause visual impairment.

PMID- 9569405
TI  - Resource allocation to health authorities. Expenditure on private health care
      must be taken into account.

PMID- 9569406
TI  - BMA cannot bring proceedings arising out of incidents in other countries.

PMID- 9569407
TI  - First pill for male impotence approved in US.

PMID- 9569408
TI  - WHO reaffirms commitment to women's health.

PMID- 9569409
TI  - Australian government launches inquiry into healthcare system.

PMID- 9569411
TI  - Health action zones set up.

PMID- 9569410
TI  - Surgeon blamed beginner's bad luck for cardiac deaths.

PMID- 9569412
TI  - Sackings and strikes paralyse Nicaraguan health care.

PMID- 9569413
TI  - Companies still breaking milk marketing code.

PMID- 9569414
TI  - US eases sanctions on Cuba.

PMID- 9569415
TI  - Commentary: promising results but wider recruitment needed.

PMID- 9569416
TI  - Preventing RhD haemolytic disease of the newborn. RhD negative women who have
      intrauterine death may need anti-D immunoglobulin.

PMID- 9569417
TI  - Preventing RhD haemolytic disease of the newborn. Guidelines are not followed in
      many cases.

PMID- 9569418
TI  - Preventing RhD haemolytic disease of the newborn. Women should be counselled
      about source of anti-D immunoglobulin.

PMID- 9569419
TI  - Preventing RhD haemolytic disease of the newborn. New recommendations must be
      explained to GPs and midwives.

PMID- 9569420
TI  - What investigations and procedures do patients in hospices want. Providing
      ineffective treatment is futile.

PMID- 9569421
TI  - What investigations and procedures do patients in hospices want. Patients with
      untreatable cancer almost never survive cardiopulmonary resuscitation.

PMID- 9569422
TI  - What investigations and procedures do patients in hospices want. Doctors are
      under no legal obligation to provide ineffective treatment.

PMID- 9569423
TI  - What investigations and procedures do patients in hospices want. Questions to
      patients and nurses should have been identical.

PMID- 9569425
TI  - Clinician scientists face difficult future.

PMID- 9569424
TI  - What investigations and procedures do patients in hospices want. Responses are
      not comparing like with like.

PMID- 9569427
TI  - Are part time doctors better doctors? Doctors need flexible training and flexible
      jobs.

PMID- 9569426
TI  - Early discharge after stroke. Use of Barthel index was not appropriate.

PMID- 9569428
TI  - Acute excited states and sudden death. Acute excited states are not caused by
      high blood concentrations of cocaine.

PMID- 9569429
TI  - Many third molar teeth are probably removed unnecessarily in Sandwell.

PMID- 9569430
TI  - Base-compositional biases and the bat problem. I. DNA-hybridization melting
      curves based on AT- and GC-enriched tracers.
AB  - We explored the interordinal relationships of mammals using DNA-DNA
      hybridization, with particular reference to the much-debated problem of whether
      the megabats and microbats are more closely related to each other than the
      megabats are to primates. To try to improve resolution when taxa are distantly
      related and the melting points of hybrids are low and difficult to distinguish,
      we increased the GC content of DNA by a fractionation method that used the same
      melting-point apparatus used in the hybridization studies. When we used GC-rich
      DNA as the tracer to make hybrids, the melting point of the self-hybrid shifted
      to a higher temperature as expected, but the behaviour of heterologous hybrids
      varied with the taxa being compared. When the melting point of the heterologous
      hybrid also shifted to a higher temperature so that the two compared taxa
      maintained the same or proportional distance, we called this 'following
      behaviour', because the heterologous hybrid made with GC-rich tracer 'followed'
      the GC-rich self-hybrid to higher temperatures. We also commonly saw anomalous
      behaviour, where the melting point of the heterologous hybrid shifted to a lower
      temperature when compared with an AT-rich hybrid. In these anomalous cases, the
      distance measured between the taxa increased markedly as a result of GC
      enrichment, indicating that an underestimate of distance may have resulted from
      AT bias in DNA. This inference was supported by the finding that it was rare to
      observe a decrease in measured distance between taxa using GC-rich DNA, but very
      common to find an increase as would be expected from the generally higher AT
      contents of eutherian DNAs. Moreover, the most extreme cases, where distances
      changed most using GC-rich DNA, were usually those involving comparisons between
      taxa known to have the most extreme AT-biases among mammals, such as the megabats
      and rhinolophoid (including megadermatid) microbats. Our results show consistent
      underestimates of measured differences between eutherian taxa with extreme AT
      biases.

PMID- 9569431
TI  - Base-compositional biases and the bat problem. II. DNA-hybridization trees based
      on AT- and GC-enriched tracers.
AB  - We conducted a series of parallel DNA-hybridization experiments on a small group
      of bats (species of Pteropus, Rhinolophus, Noctilio and Pteronotus) and outgroups
      (Lemur, Cynocephalus, Didelphis), using whole-genome labels and tracers made from
      extracts enriched with AT and two levels of GC content. FITCH (additive
      phylogenetic trees) topologies were constructed from the four sets of
      comparisons, indexed as both delta Tmode and delta NPHs (normalized percentage of
      hybridization). Based on our previous work showing that the shared AT bias of
      pteropodids and some microchiropterans may affect the rank-ordering of taxa based
      on either AT- or GC-rich labels, our expectation was that the resulting trees
      would show differing topologies when generated from tracers made with the
      variously enriched DNA extracts. Whereas there was some variation among the
      trees, most of them grouped the bats together, and almost all paired the
      representative megachiropteran and rhinolophoid microchiropteran as sister-taxa
      in contrast to the other microchiropterans. As the pteropodid-rhinolophoid
      relationship is an unexpected and unlikely one, we attribute this association to
      an AT bias that was not obviated even by our most GC-rich labels, and suggest
      that such a bias may compromise the truth of some molecular trees. Accordingly,
      we believe the broader issue of bat monophyly remains unresolved by DNA
      hybridization and probably also by gene-sequencing studies.

PMID- 9569432
TI  - The coevolution of human fertility and wealth inheritance strategies.
AB  - Life history theory concerns the scheduling of births and the level of parental
      investment in each offspring. In most human societies the inheritance of wealth
      is an important part of parental investment. Patterns of wealth inheritance and
      other reproductive decisions, such as family size, would be expected to influence
      each other. Here I present an adaptive model of human reproductive decision
      making, using a state-dependent dynamic model. Two decisions made by parents are
      considered: when to have another baby, and thus the pattern of reproduction
      through life; and how to allocate resources between children at the end of the
      parents' life. Optimal decision rules are those that maximize the number of
      grandchildren. Decisions are assumed to depend on the state of the parent, which
      is described at any time by two variables: number of living sons, and wealth. The
      dynamics of the model are based on a traditional African pastoralist system, but
      it is general enough to approximate to any means of subsistence where an increase
      in the amount of wealth owned increases the capacity for future production of
      resources. The model is used to show that, in the unpredictable environment of a
      traditional pastoralist society, high fertility and a biasing of wealth
      inheritance to a small number of children are frequently optimal. Most such
      societies are now undergoing a transition to lower fertility, known as the
      demographic transition. The effects on fertility and wealth inheritance
      strategies of reducing mortality risks, reducing the unpredictability of the
      environment and increasing the costs of raising children are explored. Reducing
      mortality has little effect on completed family sizes of living children or on
      the wealth they inherit. Increasing the costs of raising children decreases
      optimal fertility and increases the inheritance left to each child at each level
      of wealth, and has the potential to reduce fertility to very low levels. The
      results offer an explanation for why wealthy families are frequently also those
      with the smallest number of children in heterogeneous, post-transition societies.

PMID- 9569433
TI  - Diagnosing acute maxillary sinusitis in primary care: a comparison of ultrasound,
      clinical examination and radiography.
AB  - In primary care, acute maxillary sinusitis may be diagnosed by clinical
      examination, ultrasound or radiography. Previous studies on the diagnostic
      accuracy of these methods are from secondary care settings and may not be
      generalisable to primary care. In this study of 39 primary care patients we have
      compared ultrasound, clinical examination and radiography to sinus irrigation.
      The sensitivity of ultrasound performed by general practitioners is 61% and
      specificity is 53%. Diagnostic accuracy does not improve when the general
      practitioner bases the diagnosis on combination of clinical examination and
      ultrasound. The most accurate way to diagnose sinusitis is radiography and when
      the radiographs are interpreted by a radiologist (sensitivity: 61%; specificity:
      98%). The accuracy of the ultrasound examination performed by general
      practitioners is poorer than earlier results from ENT practices. More attention
      should be paid to education and quality management in the use of ultrasound in
      primary care.

PMID- 9569434
TI  - Antibiotic treatment of patients with mucosal thickening in the paranasal
      sinuses, and validation of cut-off points in sinus CT.
AB  - We compared the efficacy of penicillin V and amoxycillin treatment with placebo
      in 70 adult patients from Norwegian family practice with a clinical diagnosis of
      acute sinusitis and mucosal thickening on CT, but without fluid level or total
      opacification. The study was randomized and double-blind. Three different
      outcomes were evaluated; subjective status after 10 days of treatment, difference
      in clinical score between day 0 and day 10, and duration of the illness episode.
      Amoxycillin and penicillin V gave no better response to treatment than placebo,
      evaluated by all three outcome measures. The median duration of the sinusitis
      episode was 10 days in the amoxycillin- and placebo groups and 13 days in the
      penicillin-V group. In patients with a clinical diagnosis of acute sinusitis,
      fluid level and total opacification on CT are good criteria to differentiate
      between groups of patients that need or do not need antibiotic treatment.

PMID- 9569435
TI  - Cancer of the nasal cavity and paranasal sinuses: a series of 115 patients.
AB  - A total of 115 patients with sinonasal cancer was assessed during the period 1978
      1995. Ninety-one patients received treatment with curative intent. A combination
      of irradiation and operation was used. The 5-year crude survival for patients,
      who were treated with curative intent, was 41%; the disease-specific survival
      throughout the period was 48%. Primary irradiation followed by maxillectomy was
      widely used in the first half of the period. Treatment in the last part was
      changed to primary lateral rhinotomy with post-operative irradiation whenever
      possible. Twelve maxillectomies were performed during the first half of the
      period, and during the last part, only two. Disease-specific survival was equal
      in the first and the second halves of the period.

PMID- 9569436
TI  - Olfactory function after functional endoscopic sinus surgery for chronic
      sinusitis.
AB  - One hundred and fifteen patients suffering from chronic sinusitis were observed
      to analyse the prevalence of olfactory dysfunction and the influence of FESS. Pre
      operative questionnaires were supplemented by examination of olfactory thresholds
      and discrimination. Pre-operatively, 58% of the collective were aware or
      complained of any olfactory deficit. However, the olfactory tests demonstrated
      that of the collective 52% were hyposmic and 31% anosmic. Eight per cent of the
      hyposmic patients presented with an isolated reduction of their ability to
      discriminate odours. Post-operative improvements were found in 70%. Normosmia was
      post-operatively achieved in 25% of the hyposmic patients, but only in 5% of the
      anosmic patients. Olfaction changed to the worse in 8% after FESS. Therefore, the
      prevalence of olfactory dysfunction in chronic sinusitis is pre-operatively
      higher, and the rate of improvement is lower than generally assumed. The extent
      of sinus disease as measured by the degree of intranasal polyposis correlates
      with olfactory dysfunction. Resections of the middle turbinate may have a
      negative effect on olfaction, due to damage to the olfactory fila or alteration
      of the normal aerodynamic pattern within the olfactory cleft. However, this
      hypothesis is based on a few observations and needs to be verified by further
      investigations.

PMID- 9569437
TI  - The role of ethmoid sinus surgery in the treatment of the twisted nose.
AB  - The correction of the twisted nose remains a challenge from both the functional
      and aesthetic points of view. It is well recognized that complete correction of
      this nasal deformity often necessitates not only reconfiguration of the external
      nasal framework, but also realignment of the septum. The occasional patient will,
      in addition, require concurrent middle turbinate resection and/or ethmoidectomy
      to enable one to achieve full correction of both his/her external and septal
      deformities. We will briefly outline the rationale for this approach w ith an
      illustrative case example.

PMID- 9569438
TI  - The impact of outdoor pollution on upper respiratory diseases.
AB  - We evaluated the prevalence of upper airway diseases among two groups living in
      areas with different pollution levels. The study was conducted among highschool
      students living in Bayrampasa (an area polluted by SO2 and total suspended
      particulates) and Beykoz (an unpolluted residential area) in Istanbul (n = 386).
      Each subject filled out a standardized zelf-administered questionnaire. Also,
      anterior active rhinomanometry was performed to objectively evaluate the symptoms
      in all students. A significantly higher prevalence rate for rhinitis was found in
      Bayrampasa, as compared to Beykoz. However, the prevalence rate for pharyngitis
      was not significantly different between both groups. Smoking was more frequent in
      the unpolluted area. Exposure to parental smoking in childhood and heating
      systems in houses were evenly distributed. Household crowding was lower in
      Beykoz. Rhinomanometric measurements did not show any significant difference
      between both groups. Multiple logistic regression models estimating the role of
      each risk factor independently, showed a significant odds ratio associated with
      residence in Bayrampasa for rhinitis (OR: 2.0; 95% CI: 3.0-1.3). In conclusion,
      this study indicates that outdoor pollution has adverse effects on the degree of
      upper airway diseases in Istanbul in the 1990s.

PMID- 9569439
TI  - Comparison of calculated nasal resistance from Rohrer's equation with measured
      resistance at delta P150Pa.
AB  - Values of nasal resistance at delta P150Pa have been recommended by the
      International Standardization Committee for clinical use. However, this point
      seems somewhat high for quiet nasal breathing. To determine the usefulness of
      calculated nasal resistance at delta P150Pa from Rohrer's equation when
      transnasal pressure fails to reach the point, the values at delta P150Pa
      calculated from the method have been compared with actually measured nasal
      resistances at delta P150Pa by active anterior rhinomanometry with a nasal
      nozzle. The mean value of measured unilateral nasal resistance in 75 patients is
      0.513 +/- 0.511 Pa/cm3/s on expiration and 0.335 +/- 0.193Pa/cm3/s on
      inspiration. The mean value of calculated nasal resistance from Rohrer's equation
      is 0.511 +/- 0.515Pa/cm3/s on expiration and 0.337 +/- 0.207Pa/cm3/s on
      inspiration. Correlations between measured and calculated nasal resistances have
      been assessed and are almost identical in both expiration and inspiration.
      Calculated nasal resistance at delta P150Pa from Rohrer's equation seems to be
      suitable for evaluation when transnasal pressure fails to attain the point.

PMID- 9569440
TI  - Psychosocial consequences of nasal aesthetic and functional surgery: a controlled
      prospective study in an ENT setting.
AB  - Much still needs to be known about what motivates and goes through patients'
      minds when undergoing nasal aesthetic surgery. Little is also known on how the
      aesthetic change affects the way other people see those patients after surgery,
      and if the improved appearance significantly benefits the patients' psychosocial
      functioning. So far, research has largely focused on subjects in Plastic Surgery
      settings, neglecting to investigate the specificities of rhinoplasty as performed
      by otolaryngologists. In order to elucidate these, a prospective controlled-study
      design was developed. Twenty-five consecutive patients, selected from an ENT
      practice for septorhinoplasty, were enrolled. They were submitted to pre
      operative psychiatric interviews and psychological tests. Two control groups were
      simultaneously enlisted, and were submitted also to the same tests. Four to seven
      months after surgery, the septorhinoplasty patients were again evaluated by
      psychiatric interviews and psychological tests as well as asked to fill out a
      questionnaire addressing subjective satisfaction with the surgical results. They
      also underwent, at that time, a rhinomanometric examination assessing the
      objective success of surgery on nasal function. It was concluded that the study
      population was basically a psychologically well balanced group of patients, and
      that a successful surgical result could indeed, in some, improve pre-operative
      psychological "suffering" related to the nasal deformity, and give these patients
      a new social identity. Ultimately, it was found that the meeting of aesthetic
      requirements, frequently not put forward by the patient preoperatively, was the
      single most important factor required for a final complete satisfaction with the
      overall surgical results in this population.

PMID- 9569441
TI  - Lateral canthotomy: a simple and safe procedure for orbital haemorrhage secondary
      to endoscopic sinus surgery.
AB  - Two cases of orbital complications secondary to functional endoscopic sinus
      surgery are presented. One case was complicated in the immediate post-operative
      period with an orbital haematoma, which required urgent decompression using
      lateral canthotomy. The second case had presented an acute orbital haemorrhage
      during functional endoscopic sinus surgery, which required the same surgical
      procedure. These cases demonstrate that lateral canthotomy constitutes a safe and
      fast surgical procedure to decrease the intraorbital pressure.

PMID- 9569442
TI  - Pneumosinus dilatans: a discussion of four cases and the possible aetiology.
AB  - Pneumosinus dilatans is an abnormal dilatation of the paranasal sinuses, which
      contains only air and is lined by normal mucosa. It is a rare condition, the
      aetiology of which is unclear. We describe four patients who presented to our
      department with pneumosinus dilatans. The aetiology was either developmental
      hydrocephalus (n = 1), post-traumatic (n = 1) or idiopathic (n = 2). Two patients
      underwent surgery, and follow-up is at least 12 months to date. The radiological
      aspects of this rare condition and the possible aetiologies are discussed.

PMID- 9569443
TI  - Association of rhinoscleroma with rhinosporidiosis.
AB  - Rhinoscleroma caused by the bacillus Klebsiella rhinoscleromatis and
      rhinosporidiosis caused by the fungus Rhinosporidium seebri are rare, specific
      nasal infections, both of which have a certain geographical distribution. To the
      best of our knowledge no association between them has been reported in the
      international literature. We have documented such an association in two male
      Indian patients aged-32 and 27 years, respectively-both presenting with
      unilateral blood-stained discharge and nasal blockage. They showed strawberry
      like polypoidal masses, and histological examination confirmed the diagnosis.
      Klebsiella rhinoscleromatis was cultured twice in the first case. The patients
      were treated with complete excision and a long course of septrin, for which
      Klebsiella rhinoscleromatis is sensitive. The purpose of this paper is to report
      the first association of these two granulomatous infections, to show the impact
      of immigration on the differential diagnosis, and to review the relevant
      literature.

PMID- 9569445
TI  - The National Exposure Registry: analyses of health outcomes from the benzene
      subregistry.
AB  - The purpose of the National Exposure Registry is to assess the long-term health
      consequences to a general population from long-term, low-level exposures to
      specific substances in the environment. This study investigates the health
      outcomes of 1,143 persons (1,127 living, 16 deceased) living in south central
      Texas who had documented environmental exposure to benzene (up to 66ppb) in tap
      water. As with all subregistries, face-to-face interviews were used to collect
      self-reported information for 25 general health status questions. Using computer
      assisted telephone interviewing, the same health questions were asked 1 year
      (Followup 1, F1) and 2 years later (Followup 2, F2). The health outcome rates for
      Baseline and Followup 1 and 2 data collections for the Benzene Subregistry were
      compared with national norms, that is, the National Health Interview Survey
      (NHIS) rates. For at least one of the three reporting periods, specific age and
      sex groups of the Benzene Subregistry population reported more adverse health
      outcomes when compared with the NHIS population, including anemia and other blood
      disorders, ulcers, gall bladder trouble, and stomach or intestinal problems,
      stroke, urinary tract disorders, skin rashes, diabetes, kidney disease, and
      respiratory allergies. Statistically significant deficits for the Benzene
      Subregistry population overall were found for asthma, emphysema, or chronic
      bronchitis; arthritis, rheumatism, or other joint disorders; hearing impairment;
      and speech impairment. No statistically significant differences between the two
      populations were seen for the outcomes hypertension; liver disease; mental
      retardation; or cancer. These results do not identify a causal relationship
      between benzene exposure and adverse health effects; however, they do reinforce
      the need for continued followup of registrants.

PMID- 9569446
TI  - Role of risk assessment in public health practice.

PMID- 9569444
TI  - Health effects of cadmium exposure--a review of the literature and a risk
      estimate.
AB  - This report provides a review of the cadmium exposure situation in Sweden and
      updates the information on health risk assessment according to recent studies on
      the health effects of cadmium. The report focuses on the health effects of low
      cadmium doses and the identification of high-risk groups. The diet is the main
      source of cadmium exposure in the Swedish nonsmoking general population. The
      average daily dietary intake is about 15 micrograms/day, but there are great
      individual variations due to differences in energy intake and dietary habits. It
      has been shown that a high fiber diet and a diet rich in shellfish increase the
      dietary cadmium intake substantially. Cadmium concentrations in agricultural soil
      and wheat have increased continuously during the last century. At present, soil
      cadmium concentrations increase by about 0.2% per year. Cadmium accumulates in
      the kidneys. Human kidney concentrations of cadmium have increased several fold
      during the last century. Cadmium in pig kidney has been shown to have increased
      by about 2% per year from 1984-1992. There is no tendency towards decreasing
      cadmium exposure among the general nonsmoking population. The absorption of
      cadmium in the lungs is 10-50%, while the absorption in the gastrointestinal
      tract is only a few percent. Smokers have about 4-5 times higher blood cadmium
      concentrations (about 1.5 micrograms/l), and twice as high kidney cortex cadmium
      concentrations (about 20-30 micrograms/g wet weight) as nonsmokers. Similarly,
      the blood cadmium concentrations are substantially elevated in persons with low
      body iron stores, indicating increased gastrointestinal absorption. About 10-40%
      of Swedish women of child-bearing age are reported to have empty iron stores (S
      ferritin < 12 micrograms/l). In general, women have higher concentrations of
      cadmium in blood, urine, and kidney than men. The population groups at highest
      risk are probably smokers, women with low body iron stores, and people habitually
      eating a diet rich in cadmium. According to current knowledge, renal tubular
      damage is probably the critical health effect of cadmium exposure, both in the
      general population and in occupationally exposed workers. Tubular damage may
      develop at much lower levels than previously estimated, as shown in this report.
      Data from several recent reports from different countries indicate that an
      average urinary cadmium excretion of 2.5 micrograms/g creatinine is related to an
      excess prevalence of renal tubular damage of 4%. An average urinary excretion of
      2.5 micrograms/g creatinine corresponds to an average concentration of cadmium in
      renal cortex of 50 micrograms/g, which would be the result of long-term (decades)
      intake of 50 micrograms per day. When the critical concentrations for adverse
      effects due to cadmium accumulation are being evaluated, it is crucial to
      consider both the individual variation in kidney cadmium concentrations and the
      variations in sensitivity within the general population. Even if the population
      average kidney concentration is relatively low for the general population, a
      certain proportion will have values exceeding the concentration where renal
      tubular damage can occur. It can be estimated that, at the present average daily
      intake of cadmium in Sweden, about 1% of women with low body iron stores and
      smokers may experience adverse renal effects related to cadmium. If the average
      daily intake of cadmium would increase to 30 micrograms/day, about 1% of the
      entire population would have cadmium-induced tubular damage. In risk groups, for
      example, women with low iron stores, the percentage would be higher, up to 5%.
      Both human and animal studies indicate that skeletal damage (osteoporosis) may be
      a critical effect of cadmium exposure. We conclude, however, that the present
      evidence is not sufficient to permit such a conclusion for humans. We would like
      to stress, however, that osteoporosis is a very important public health problem
      worldwide, but especially in the Scandinav

PMID- 9569447
TI  - Acute intravenous and inhalation pharmacokinetics of 2,4-pentanedione in the
      Fischer 344 rat.
AB  - 2,4-Pentanedione (2,4-PD; CAS No. 123-54-6), an industrial chemical, was
      investigated for its comparative pharmacokinetics in male Fischer 344 rats by a
      single intravenous (i.v.) injection of (4.3, 43, 148.5, and 430 mg/kg), or a 6-hr
      nose-only inhalation exposure (400 ppm) to 14C-2,4-PD. For the i.v. route, the
      plasma concentration of 14C-2,4-PD-derived radioactivity declined in a
      biexponential fashion. The overall form of the 14C plasma concentration-time
      curves and derived pharmacokinetic parameters indicated that dose-linear kinetics
      occurred in the i.v. dose range 4.3-148.5 mg/kg, but not with 430 mg/kg.
      Metabolism of 2,4-PD was quite rapid as the concentration of unmetabolized 2,4-PD
      declined steadily to undetectable after 8 hr. 14C-2,4-PD derived radioactivity
      was eliminated mainly as 14CO2 and in urine. For the 4.3, 43 and 148.5 mg/kg
      doses 14CO2 elimination was relatively constant (36.8, 38.8 and 42.3% in 48 hr
      samples respectively) and greater than urinary excretion (17.9, 14.3 and 29.6%;
      48 hr specimens). At 430 mg/kg i.v. there was a reversal of the excretion
      pattern, with urine 14C excretion (54.7%) becoming greater than that for 14CO2
      (27.3%). Excretion in expired volatiles and feces was small. Radiochromatograms
      of urine showed free 2,4-PD in the 12 hr sample, together with 7 other
      metabolites. Free 2,4-PD and 6 of the metabolites decreased or were not
      detectable in a 24 or 48 hr urine sample, but one peak (retention 7.9 min)
      increased progressively to become the major fraction (97%). Nose-only exposure to
      400 ppm 14C-2, 4-PD produced a mean decrease in breathing rate of 20.1%, which
      was constant and sustained throughout exposure, due to a lengthening of the
      expiratory phase of the respiratory cycle. 14C-2,4-PD was rapidly absorbed during
      the first 3 hr of exposure, then began to plateau, but did not reach a steady
      state. Postexposure elimination of 14C from plasma followed a biexponential form
      with a t1/2 for the terminal disposition phase of 30.72 hr. Plasma unmetabolized
      2,4-PD was present throughout the whole of the exposure phase, but was
      significantly less than total 14C. Postexposure, plasma unmetabolized 2,4-PD
      declined rapidly to undetectable concentrations by 12 hr. Radiolabel excretion
      was approximately equivalent in urine (37.6%) and expired 14CO2 (36.3%). Urine
      radiochromatograms showed a minor 2,4-PD contaminant (0.6-5.9% over 48 hr), along
      with 7 other peaks probably representing metabolites. As with the 148.5 mg/kg
      i.v. dose, the major metabolite peak was at 7.8 min retention, increasing from
      41.1% (12 hr) to 62.8% (48 hr). Immediately postexposure, radioactivity was
      present in all tissues examined, but on a concentration basis (microgram equiv/g)
      there was no preferential accumulation of 14C in any tissue or organ. On a total
      organ basis, highest contents were in liver and kidney, presumably related to the
      metabolism and excretion of 2,4-PD. By 48 hr postexposure, concentrations had
      decreased in all tissues except fat, presumably due to the lipophilicity of 14C
      residues. The profile of the plasma-time radioactivity curves, and the presence
      of residual radioactivity in tissues at 48 hr postexposure, suggests that a
      cumulative process could occur with frequent repeated exposures.

PMID- 9569448
TI  - Application of health information to hazardous air pollutants modeled in EPA's
      Cumulative Exposure Project.
AB  - Relatively little is known about the spectrum of health effects, and the scope
      and level of ambient air concentrations of those pollutants regulated under the
      Clean Air Act as "hazardous air pollutants". The U.S. Environmental Protection
      Agency's (USEPA) Cumulative Exposure Project uses currently available emissions
      inventories, from a variety of source types, and an atmospheric dispersion model
      to provide estimates of ambient concentrations for 148 hazardous air pollutants
      (HAPs) in over 60,000 census tracts for the year 1990. This paper uses currently
      available hazard information for those pollutants and provides a database of
      potential regulatory threshold concentrations of concern, or "benchmark
      concentrations," and a methodology for prioritizing and characterizing the
      quality of the data. In order to demonstrate application of the database and
      prioritization scheme to outputs from the Cumulative Exposure Project,
      comparisons were made with the maximum modeled concentration of each individual
      hazardous air pollutant across the census tracts. Of the 197 benchmark
      concentrations for cancer and non-cancer (long- and short-term exposures) effects
      compiled for the study, approximately one half were exceeded with a predominance
      of exceedance of cancer benchmarks. While the number of benchmark concentrations
      available to fully characterize potential health effects of these pollutants was
      limited (approximately 80 percent of HAPs identified as cancer concerns had
      benchmark concentrations for cancer and 50 percent of all HAPs had non-cancer
      benchmark concentrations) and there was greater uncertainty in derivation of
      maximum modeled air concentrations than other levels, the comparison between the
      two was a useful approach for providing an indication of public health concern
      from hazardous air pollutants.

PMID- 9569449
TI  - Health effects classification and its role in the derivation of minimal risk
      levels: neurological effects.
AB  - The agency for Toxic Substances and Disease Registry (ATSDR) uses substance
      specific minimal risk levels (MRLs) to assist in evaluating public health risks
      associated with exposure to hazardous substances. By definition, "MRLs are
      estimates of daily human exposure to a chemical that are likely to be without an
      appreciable risk of adverse noncancer health effects over a specified duration of
      exposure." MRLs serve as screening levels for health assessors to identify
      contaminants and potential health effects that may be of concern for population
      living near hazardous waste sites and chemical releases. MRLs for each substance
      are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365
      days and longer) exposure durations, and for the oral and inhalation routes of
      exposure. The MRLs are derived from data compiled from a current comprehensive
      literature search and are presented in ATSDR's toxicological profile for that
      substance. In this paper we outline ATSDR's guidance for evaluating the
      neurological end point as discussed in the agency's toxicological profiles.
      Ranking neurological effects into less serious and serious categories and
      applying this procedure to the derivation of health guidance values or MRLs are
      also described. Specific examples of ATSDR MRLs based on neurological effects are
      presented.

PMID- 9569450
TI  - Effects of cadmium on liver function in diabetic rats.
AB  - Hepato-toxicity of cadmium in alloxan induced diabetic rats has been studied by
      estimating a few enzymes viz serum glutamic oxalacetic transaminase, glutamic
      pyruvic transaminase, alkaline phosphatase and gamma-glutamyltranspeptidase.
      Present results suggest that cadmium manifests different effects in normal and
      diabetic rats. Insulin therapy helps in restoring the liver function. It is
      suggested that an isozyme of cytochrome P450 that appears in diabetic rats might
      be responsible for altered toxicity of cadmium.

PMID- 9569452
TI  - Screening blood for viral genomes: which way to go?

PMID- 9569451
TI  - Serious bacterial complications from blood components--how do they occur?

PMID- 9569453
TI  - Nucleic acid technology (NAT) testing and the transfusion service: a rationale
      for the implementation of minipool testing.

PMID- 9569454
TI  - Fatal reaction to transfusion of red-cell concentrate contaminated with Serratia
      liquefaciens.
AB  - A 60-year-old woman undergoing surgery died from endotoxic shock and DIC after
      receiving a 19-day-old unit of optimal additive red-cell concentrate found
      contaminated with Serratia liquefaciens. No source of contamination could be
      found. This normally free-living organism is usually of low pathogenicity. It is
      a very unusual contaminant of stored donated blood, although it appears to be on
      the increase. When transfused, blood contaminated with S. liquefaciens always
      causes severe morbidity and is associated with a high death rate. This is the
      fifth report in the English literature.

PMID- 9569455
TI  - Fatal Clostridium perfringens sepsis from a pooled platelet transfusion.
AB  - A male patient with acute myeloid leukaemia received a pooled platelet
      preparation prepared by Optipress system on the last day of its shelf life. The
      patient collapsed after two-thirds of the contents had been transfused.
      Clostridium perfringens was isolated from the platelet bag within 18 h of the
      acute event. Metronidazole, gentamicin and Clostridium antiserum were then
      administered in addition to the broad spectrum antibiotics started previously.
      However, the patient died 4 days after the platelets were transfused. The cause
      of death was given as cardiovascular shock, entirely compatible with an
      overwhelming bacteraemic and septic episode. A coroner's verdict of accidental
      death due to transfusion of a contaminated unit of platelets was recorded. On
      subsequent investigation Cl. perfringens type A serotype PS68,PS80 (identical to
      that found in the platelet bag) was cultured from the venepuncture site of the
      arm of one of the donors who contributed towards the platelet pool. The donor had
      two young children and frequently changed nappies. Faecal contamination of the
      venepuncture site was the suspected source for the transmission of Cl.
      perfringens, an organism commonly found in the soil and intestinal tract of
      humans. This case dramatically highlights the consequences of transfusing a
      bacterially contaminated unit. It is vital that such incidents are investigated
      and reported so that the extent of transfusion-associated bacterial transmission
      can be monitored and preventative measures taken if possible.

PMID- 9569456
TI  - Preoperative autologous blood deposition in support of gynaecological repair
      procedures.
AB  - Autologous blood transfusion was evaluated in gynaecological repair procedures
      including abdominal/ vaginal hysterectomy with vaginal repair, post-hysterectomy
      vaginal suspension and fixation, uni/bilateral salpingo-oophorectomy with vaginal
      colpopexy and sling procedures. A total of 247 autologous units were collected
      from 95 patients at the regional blood centre with 1-3 units (mean 2-6 units)
      deposition from each patient. One hundred and ninety of all collected units were
      transfused (collection/transfusion ratio = 1.3). Of these patients, 86 (90.5%)
      received autologous blood; 12 (13%) being transfused with 1 unit, 44 (46%) with 2
      units and 30 (32%) with 3 units. Two of these patients received additional
      homologous blood. The average preoperative haemoglobin level was 119 g L-1 and
      average post-operative haemoglobin level was 105 gL-1. The post-operative Hb
      level was used as a retrospective indicator for the requirement for blood
      transfusion. The results show that overall 75% of patients had post-operative
      haemoglobin levels < or = 110 and 33% of patients with Hb levels < 100,
      respectively. These results suggest that preoperative autologous blood deposition
      may be appropriate in the patients undergoing reconstructive gynaecological
      repair procedures since there was a high rate of usage of autologous blood and
      low post-operative haemoglobin in a significant proportion of patients.

PMID- 9569457
TI  - Transfusion of white-cell containing allogeneic blood components and
      postoperative wound infection: effect of confounding factors.
AB  - Randomized controlled trials (RCTs) of the relationship between allogeneic
      transfusion and post-operative bacterial infection at any site have generated
      discordant results, but have suggested an association of transfusion with wound
      infection. To examine the specific association of perioperative transfusion with
      wound infection, we reviewed the records of 964 consecutive patients undergoing
      elective colorectal cancer resection at our hospital. Diagnoses of wound
      infection were made retrospectively by the Centers for Disease Control criteria,
      and transfusion was defined as number of units of white-cell containing
      allogeneic blood components received. The probability of wound infection in
      association with the transfusion was calculated following adjustment for the
      effects of 12 confounders that had not been previously considered in combination.
      These factors related to severity of illness, difficulty of operation and risk of
      wound infection. Wound infection developed in 39 (11.4%) transfused patients, as
      compared to 24 (3.9%) untransfused subjects (P < 0.0001). In the multivariate
      analysis, there was a trend suggesting an adverse transfusion effect, which
      amounted to a 7% increase in the risk of wound infection per unit of red cells or
      platelets transfused (relative risk [RR] = 1.07; 95% confidence interval for RR =
      0.98-1.16; P = 0.1241). This marginally significant effect was related to post
      operative (P = 0.1274), rather than perioperative (P = 0.3061), transfusion. We
      conclude that allogeneic transfusion may perhaps be associated with a small
      increase in the risk of post-operative wound infection, but this small effect can
      be established only by RCTs enrolling several thousand patients. The modest
      magnitude of the effect may have been responsible for the disagreements among the
      published RCTs.

PMID- 9569458
TI  - Clinical use of FFP: results of a retrospective process and outcome audit.
AB  - An audit has been carried out on the usage of 216 units of fresh frozen plasma
      (FFP) issued to 41 patients. This involved the systems of FFP issue, the
      appropriateness of prescription as well as the recorded benefits. Sixty-six per
      cent of the initial requests for FFP appeared to satisfy criteria for appropriate
      use. Review of the case notes resulted in some changes to earlier decisions and a
      slight increase to 73% of those accepted as valid. Only 94% of the FFP issued
      could be proved to have been given to identified patients and only 88% of case
      notes showed the reason for treatment. Pre- and post-treatment coagulation
      results were available for all patients. In 15% of cases, pretreatment results
      were not significantly abnormal, and consequently no post-treatment improvement
      found. Coagulation improvement was documented in 78% of cases, and clinical
      statements on patient progress noted in 40%. In 80% of cases, the patient
      received other blood products carrying a potential virus risk. Six of the
      remaining eight patients were treated to stabilize oral anticoagulation. For
      these patients, virus-inactivated prothrombin concentrates could have been used,
      resulting in almost the same reduction in virus transmission risk for the group
      of 41 patients as could be obtained by using virus-inactivated FFP.

PMID- 9569459
TI  - Transfusing platelets 2 h after the completion of amphotericin-B decreases its
      detrimental effect on transfused platelet recovery and survival.
AB  - Platelet transfusion support is required during bone marrow aplasia following
      ablative chemotherapy and bone marrow progenitor cell transplantation (BMT).
      Amphotericin-B is frequently given to these patients, both therapeutically and
      prophylactically, and has been described to have a negative impact on the results
      of platelet transfusions. We conducted a prospective study of the effect of
      amphotericin-B on transfused platelet recovery and survival in 81 BMT or acute
      leukaemia patients. One hundred and ninety-five platelet transfusions
      administered to 81 consecutive patients were analysed. The platelets were
      transfused 2 h after the completion of amphotericin-B. Using this schedule
      resulted in no effect of amphotericin-B on platelet recovery or survival,
      although platelet increments were modestly depressed in patients receiving high-
      vs. low-dose amphotericin-B. We conclude that the timing of amphotericin-B
      infusion be evaluated in patients demonstrating poor platelet recovery and
      survival. Transfusing platelets at least 2 h after the completion of amphotericin
      B decreases the detrimental effect of this antifungal agent on transfused
      platelet recovery and survival.

PMID- 9569460
TI  - Supernatant from stored red cells activates neutrophils.
AB  - Bioreactive substances including cytokines and lipids accumulate during storage
      of red blood cells (RBCs) but their clinical importance is uncertain. The goal of
      this study was to evaluate the effect of stored RBC supernatant on neutrophil
      activity in vitro. Packed RBCs (PRBCs) were collected and divided into two
      aliguots, one leukodepleted and the other nonleukodepleted. Plasma supernatant
      from PRBCs were collected on days 1, 8, 15, 29 and 35 and its effect on
      neutrophil expression of CD11b, CD16 and oxidative burst was measured by flow
      cytometry. Levels of tumour necrosis factor alpha (TNF alpha) and interleukin-8
      (IL8) were also measured. The supernatant from PRBC units stored for greater than
      15 days activated and primed neutrophils as evidenced by an increase CD11b and
      CD16 expression and oxidative burst. The greatest effect was seen in the oldest
      concentrates (35-day-old) (P < 0.008). Leukodepletion abrogated the effects of
      stored supernatant on CD11b and CD16 expression (P < 0.02) but did not reduce
      priming of the neutrophil oxidative burst (P > 0.1). Very low levels of IL8 and
      TNF alpha were detected in stored supernatants. Stored PRBC supernatant contains
      substances which directly enhance neutrophil expression of adhesion protein
      CD11b, CD16 and prime neutrophil oxidative burst. The exceedingly low level of
      IL8 and TNF alpha found in this study suggests that other factors may play a more
      important role in neutrophil priming and activation.

PMID- 9569462
TI  - Guidelines on the clinical use of leucocyte-depleted blood components. British
      Committee for Standards in Haematology, Blood Transfusion Task Force.

PMID- 9569461
TI  - The distribution of the red-cell Sta (Stones) antigen among the population of
      Taiwan.

PMID- 9569463
TI  - Evaluation of B and T-cell responses in chimpanzees immunized with Hepagene, a
      hepatitis B vaccine containing pre-S1, pre-S2 gene products.
AB  - Approximately 5-10% of healthy young adults receiving the commercially available
      hepatitis B vaccine (either serum derived or recombinant) fail to mount an
      adequate immune response. This nonresponder rate has prompted the demand for more
      immunogenic vaccines. An alternative to the currently licensed hepatitis B
      vaccines is Hepagene, a novel recombinant hepatitis B vaccine containing S, pre
      S1 and pre-S2 antigenic components, produced in the mouse C127I clonal cell line
      after transfection of the cells with genes encoding the three antigens. In this
      study, chimpanzees were immunized with Hepagene to study the humoral and cellular
      immune responses to this vaccine. Two out of the three animals immunized with
      this vaccine seroconverted 4 weeks after their first injection and all of the
      animals elicited high anti-HBs levels that were maintained for at least 28-30
      weeks after their third immunization. The anti-HBs levels elicited in these
      animals protected them against an experimental challenge with HBV. Peripheral
      blood mononuclear cells (PBMCs) obtained from immunized animals could be
      stimulated in vitro by rHBsAg and peptides representing regions within all three
      of the viral envelope proteins. Additionally, an anti-id that mimics the a
      determinant in the S-region of HBsAg could also stimulate in vitro proliferation
      of PBMCs from these immune animals. These results indicate that this new
      recombinant HBV vaccine encoding all three of the surface antigen proteins is
      highly immunogenic is that it can stimulate strong cellular and humoral immune
      responses.

PMID- 9569464
TI  - Homologous and heterologous antibody response of cattle and sheep after
      vaccination with foot and mouth disease and influenza viruses.
AB  - Homologous and heterologous antibody response to FMD and influenza vaccines was
      studied in 37 calves and 45 lambs at the age of 2 months. The FMD and influenza
      monovalent killed vaccines were administered simultaneously twice. Another group
      of 18 calves was vaccinated twice, first at the age of 2 months and second at the
      age of 6 months, with trivalent FMD vaccine. The antibody titers were measured by
      ELISA and HI after second vaccination, for FMDV and influenza, respectively. The
      conclusions of this study are summarized as follows. Individuals, lambs and
      calves, that cross-respond to one heterologous serotype are liable to respond to
      another heterologous serotype of the same virus. Individuals, lambs and calves,
      showing double cross-reactivity to one virus (FMDV), are highly liable to show
      double cross-reactivity to entirely another virus (Influenza). Multivalent
      vaccines of FMDV are expected to elevate the antibody titers for at least one
      heterologous serotype (not included in the vaccine) and to detect antibodies for
      an additional heterologous serotype, not detected otherwise following monovalent
      vaccination. These results indicate the important role of the host in the
      spectrum of the specific immune response.

PMID- 9569465
TI  - Induction of anti foot and mouth disease virus T and B cell responses in cattle
      immunized with a peptide representing ten amino acids of VP1.
AB  - We previously demonstrated that the immunization of cattle with a synthetic
      peptide representing the amino acid sequence of foot and mouth disease virus
      (FMDV) type O1 Campos VP1 residues 135-160 (p135-160), containing immunodominant
      T and B epitopes, was able to induce a strong neutralizing antibody (NA)
      response. The epitope mapping of p135-160 identified T and B epitopes in the area
      restricted to amino acid residues 135-144 (Zamorano et al. 1994, Virology 201;
      1995, Virology 212). We are now reporting that, although immunization with a
      synthetic peptide covering amino acids 135-144 (p135-144) failed to elicit an
      anti-FMDV response, a synthetic peptide representing a tandem duplication of the
      VP1 epitope 135-144 (p135-144 x 2) was very efficient in inducing a strong NA
      response in cattle. Both the antibody and T cell responses elicited by p135-144 x
      2 were highly specific for the VP1 135-144 sequence since no reactivity was
      detected against synthetic peptides representing the 140-160 sequence of VP1.
      Additionally, both responses to B and T epitopes were long lasting in the
      immunized cattle. These results constitute a good example of the improvement of
      the immune response by rational handling of precisely identified B and T
      epitopes. To our knowledge, this is the shortest native amino acid sequence to
      induce a significant NA response to FMDV in cattle.

PMID- 9569466
TI  - Maternal measles antibody decay in rural Bangladeshi infants--implications for
      vaccination schedules.
AB  - Considerable numbers of measles cases occur below the target age for vaccination
      in the Indian sub-continent. The immunogenicity of measles vaccine in infancy is
      dependent on the rate of decay in maternal antibody since this antibody
      interferes with vaccine induced seroconversion. This study investigated maternal
      antibody decay in a rural population in Bangladesh and evaluated possible risk
      factors for early decay. Measles antibodies were assessed using both ELISA and
      Plaque Reduction Neutralization (PRN) test in 330 infant-mother pairs in a cross
      sectional survey. PRN was more sensitive method than ELISA for determining
      antibody levels. Antibody levels decreased rapidly in infants with increasing
      age. By the age of 5 months, 67% (28/42) infants had practically no protective
      antibody left (30 mIU ml-1 or below). Only 12% infants at 5 months of age, and 5%
      at 8 months, had levels greater than 120 mIU ml-1--stated to 'protect' children.
      Multiple regression showed that maternal age was the only variable associated
      with the level of antibody (maternal weight, height and MUAC were not
      associated), decreasing by 1.06 mIU ml-1 for each year of age (P = 0.002).
      Infant's antibody concentration decreased with age by an average 2 mIU mL-1 for
      every month of life (P < 0.0001), and was determined by the maternal antibody
      concentration (P < 0.0001) (child's length, weight, MUAC, mother's gestational
      age and parity were not associated). The relatively rapid antibody decay suggests
      that the target age for measles vaccination might be reduced. Further, as the
      cohort of vaccinated mothers enters reproductive age in Bangladesh, a more rapid
      decay of antibody may be expected in future generations of Bangladeshi children.
      The information presented here suggests that a formal trial of standard measles
      vaccine at younger ages is justified in this population as it could confer
      considerable benefit in reducing infant measles.

PMID- 9569467
TI  - Phenotypic and genotypic alterations associated with the attenuation of a
      Theileria annulata vaccine cell line from Turkey.
AB  - Attenuated vaccines, produced by prolonged in vitro culture of the macroschizont
      stage of the life-cycle, are the main method of controlling Theileria annulata
      infections. Little is known about the mechanism(s) of attenuation. Here we
      present data from a Turkish cell line demonstrating that attenuation is
      associated with reduced ability to differentiate into microschizonts and a
      reduction in matrix metalloproteinase activity. We also show that attenuation
      results in a change in the structure of the parasite population. Using the
      technique of differential mRNA display, we demonstrate that gene expression
      profiles differ between non-attenuated and attenuated macroschizont infected
      leucocytes. One differentially expressed gene is of parasite origin. These data
      are discussed in the context of a multifactorial model for virulence.

PMID- 9569468
TI  - Safety and immunogenicity of a combined five-component pertussis-diphtheria
      tetanus-inactivated poliomyelitis-Haemophilus B conjugate vaccine administered to
      infants at two, four and six months of age.
AB  - Safety, immunogenicity and lot consistency of five-component pertussis
      combination vaccine (CPDT-IPV//PRP-T) in infants were compared to that of whole
      cell pertussis combination vaccine (DPT-IPV//PRP-T), as were separate and
      combined injections of CPDT-IPV and PRP-T. No significant differences in adverse
      event rates were observed between lots of CPDT-IPV//PRP-T or between separate or
      combined injections of CPDT-IPV and PRP-T. Minor differences in antibody
      responses were observed between lots of component pertussis vaccine. Higher
      concentrations of diphtheria and tetanus antitoxins were induced by separate than
      by combined injection of CPDT-IPV and PRP-T, but no other differences in
      immunogenicity were observed. Adverse reactions were more than twice as frequent
      after whole cell than after component pertussis vaccines. Antibody responses to
      pertussis toxoid, filamentous hemagglutin and pertactin were significantly
      greater after component vaccines, while the response to type 3 poliovirus was
      higher after whole cell vaccine. No significant differences were observed for
      other vaccine components. CPDT-IPV//PRP-T was safe and immunogenic in infants.
      Antibody results were similar to those observed in a Swedish field trial that
      demonstrated CPDT to be 85% effective in preventing clinical pertussis.

PMID- 9569469
TI  - Combined intramuscular-intradermal protocol of universal neonate HB vaccination
      irrespective of mother's status of HBsAg.
AB  - To evaluate a protocol of combined intramuscular-intradermal (i.m.-i.d.)
      universal hepatitis B (HB) vaccination of neonates regardless of the mothers' HB
      surface antigen HBsAg status, 160 full-term newborn babies were sequentially
      divided into groups A and B (test and control groups). The group A babies were
      immunized by giving 30 micrograms HB vaccine i.m. within 24 h after birth and 2
      micrograms i.d. twice at 1 and 6 months of age. Group B babies were immunized by
      giving one initial dose of 30 micrograms i.m. and two booster doses of 10
      micrograms i.m. after same 0, 1, 6-month schedule. Blood samples were collected
      at birth before the first dose of the HB vaccine, at 6 months of age before the
      third dose and at 12 months. The blood samples were tested for HBsAg and anti-HBs
      by using Abbott RIA reagents. All of the 160 newborns received three doses of
      vaccine, but in only 96 of them was the blood examination completed. The positive
      rate of anti-HBs > 10 IU l-1 was 76.27 and 83.08% in groups A and B, respectively
      at 6 months, and 83.72 and 92.45%, respectively at 12 months. The geometric mean
      titres (GMT) of anti-HBs was 42.25 and 60.25 IU l-1 in groups A and B,
      respectively at 6 months, and 74.45 and 87.1 IU l-1, respectively at 12 months.
      HBsAg was negative in the two groups 6 and 12 months after birth. The chi 2 and t
      tests showed there were no significant differences in these data between the two
      groups. Thus was it demonstrated that the combined i.m.-i.d. protocol using 34
      micrograms of HB vaccine can produce a protection similar to that of the
      conventional 50 micrograms i.m. regimen, while ca on-third of the vaccine can be
      saved. The new protocol is theoretically rational and may be ideal according to
      the cost-effectiveness principle.

PMID- 9569470
TI  - Plasmodium falciparum polyoximes: highly immunogenic synthetic vaccines
      constructed by chemoselective ligation of repeat B-cell epitopes and a universal
      T-cell epitope of CS protein.
AB  - Effective immunoprophylaxis directed against the pre-erythrocytic stages of the
      malaria parasite requires a vaccine that can elicit humoral and cell mediated
      immunity in individuals of diverse genetic background. In order for a synthetic
      peptide malaria vaccine to meet these requirements, problems associated with
      genetic restriction, peptide chemistry, adjuvant formulation and physiochemical
      characterization of the final synthetic vaccine product must first be overcome.
      To address these issues, five polyoxime vaccine candidates have been constructed
      by ligating purified peptide epitopes of the P. falciparum CS protein to a
      branched template via oxime bonds. All five constructs, including two based on
      templates containing the synthetic adjuvant tripalmitoyl-S-glyceryl cysteine
      (Pam3Cys), were of sufficient purity for characterization by mass spectrometry.
      The immunogenicity of the malaria polyoximes in different murine strains was
      compared to that of multiple antigen peptide (MAP) constructs synthesized by
      standard step-wise synthesis. A tri-epitope polyoxime-Pam3Cys construct, based on
      the repeats and a universal T-cell epitope that contains both helper and CTL
      epitopes of the CS protein, was shown to be a precisely-defined synthetic malaria
      vaccine candidate that was highly immunogenic in murine strains of diverse H-2
      haplotypes.

PMID- 9569471
TI  - Nucleic acid immunization protects dogs against challenge with virulent canine
      parvovirus.
AB  - Nucleic acid vaccines (NAVs) use expression vectors encoding one or more antigen
      genes to transfect host cells inducing both humoral and cellular immunity against
      the expressed antigen. NAV offers major advantages over conventional vaccines for
      the protection of humans and animals. This study shows that a plasmid DNA
      (pGT36VP1) encoding the full length VP1 region of canine parvovirus (CPV) induces
      immunity that protects dogs against challenge with virulent virus. Five dogs
      without anti-CPV antibodies were injected at 9 months of age with increasing
      doses of pGT36VP1 or saline. NAV vaccinated dogs showed an increase of serum IgG
      titer starting 1 week post-injection which peaked at week 2 and remained
      detectable for at least 14 weeks. A second dose of NAV resulted in an anamnestic
      response within 1 week. IgG titers peaked at week 3 and 4 after the second
      injection. All pGT36VP1 vaccinated dogs were protected against infection after
      virulent CPV challenge regardless of dose and the unvaccinated control dog was
      fully susceptible. This study demonstrated for the first time that a NAV can
      protect dogs against an infectious disease.

PMID- 9569473
TI  - Intracutaneous vaccination of rabbits with the E6 gene of cottontail rabbit
      papillomavirus provides partial protection against virus challenge.
AB  - DNA vaccination of rabbit skin with the L1 gene of cottontail rabbit
      papillomavirus (CRPV) has previously been shown to induce prophylactic immunity
      against CRPV. We now describe the effects of vaccination with the CRPV E6 gene,
      using the same approach. The experimental vaccine pdCMV-E6 encoded both the
      truncated and full length forms of CRPV E6 protein. The control vaccine pCMV-beta
      encoded beta galactosidase. Rabbits were vaccinated with DNA-coated gold
      particles, using a gene gun. Each rabbit received an initial vaccination with 30
      micrograms DNA and 3 weeks later a booster vaccination, also with 30 micrograms
      DNA. pdCMV-E6-vaccinated rabbits developed E6-specific cellular immunity as
      determined by proliferation assays using peripheral blood mononuclear cells from
      animals prior to challenge, but did not develop detectable humoral immunity to E6
      proteins, as evaluated by ELISA using two different E6 antigen preparations.
      Control rabbits developed humoral immunity to beta galactosidase. All rabbits
      were challenged by infection of nine skin sites with live CRPV virus and
      monitored for papilloma formation. None of four control rabbits was protected at
      any of the challenge sites. Of six rabbits vaccinated with pdCMV-E6, two were
      completely protected and one was virtually completely protected (tiny papillomas
      at just two of nine challenge sites). These three rabbits also exhibited
      significant E6-specific in vitro proliferative responses. The four E6 DNA
      vaccinated rabbits that were not completely protected exhibited evidence of
      partial protection: some challenge sites did not form papillomas; papilloma onset
      was delayed; papilloma burden was less. These results demonstrate that partial
      prophylaxis against papillomavirus-induced disease can be achieved by
      intracutaneous vaccination with a recombinant plasmid encoding the
      papillomavirus.

PMID- 9569472
TI  - Specific cellular and humoral immune response in Balb/c mice immunised with an
      expression genomic library of Trypanosoma cruzi.
AB  - An expression genomic library of Trypanosoma cruzi (T. cruzi) constructed using
      pcDNA3 plasmid was used for the immunisation (25 micrograms) of Balb/c mice.
      Expression of T. cruzi antigens in the muscle of inoculated mice was detected by
      indirect immunofluorescence 7 days after immunisation. Specific IgG antibodies
      were significatively increased (P < 0.05) in animals that were reimmunized with
      50 micrograms of the genomic library. An antigen specific lymphoproliferative
      response was detected in one animal of the group inoculated with one dose of the
      library.

PMID- 9569474
TI  - A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in
      young adults.
AB  - This study shows that two doses of a recombinant hepatitis B vaccine (10
      micrograms or 20 micrograms of HBsAg per dose), administered 6 months apart to
      young, healthy adults, can induce an antibody (anti-HBs) response similar to that
      expected with the standard three-dose regimen of this vaccine given at intervals
      of 0, 1, and 6 months. While only 46-67% of the vaccinees displayed a protective
      anti-HBs titer of > or = 10 mIU ml-1 prior to the receipt of the second dose at 6
      months, virtually all were primed as 97-99% of the subjects developed such a
      titer when tested a month after the second dose. Among vaccinees given 10 or 20
      microgram doses, respectively, the secondary rise in antibody following the
      second dose yielded geometric mean titers (GMTs) of 1103 and 2538 mIU ml-1,
      respectively. The study further demonstrated that a two-dose regimen of
      vaccination induced strong immunologic memory for HBsAg, as a booster dose of
      vaccine given 2 years later resulted in a rapid and vigorous anamnestic antibody
      response.

PMID- 9569475
TI  - Pneumococcal conjugate vaccination in adults: circulating antibody secreting cell
      response and humoral antibody responses in saliva and in serum.
AB  - The results from our previous study showed IgA dominated ASC responses to
      pneumococcal polysaccharide vaccine and to pneumococcal polysaccharide
      meningococcal outer membrane protein conjugate vaccine (PncOMPC) in adult
      volunteers. The results indicated that a high IgA ASC response is a useful
      indicator of a secretory IgA response in saliva. We believe that the mucosal
      immune responses is potentially an important characteristic of the pneumococcal
      vaccines and should thus be measured when the new pneumococcal conjugate vaccines
      are evaluated. In the present study, we studied two new tetravalent pneumococcal
      conjugate vaccines: the diphtheria toxoid and tetanus toxoid conjugates. In
      contrast to PncOMPC, these conjugates induced higher responses than the
      polysaccharide vaccine. Furthermore, the different structure of the two conjugate
      vaccines might affect the nature of the response. Thus a different vaccine may be
      optimal for induction of a mucosal response than is of systemic responses.

PMID- 9569476
TI  - Effect of combination with an acellular pertussis, diphtheria, tetanus vaccine on
      antibody response to Hib vaccine (PRP-T).
AB  - Acellular pertussis vaccines provide protection against whooping cough with few
      adverse effects. Their introduction to routine immunisation programmes would be
      facilitated by their incorporation with other routinely administered vaccines.
      262 infants were immunised with an acellular pertussis vaccine containing
      pertussis toxin and filamentous haemagglutinin, combined with diphtheria and
      tetanus toxoids. This vaccine was mixed with Haemophilus influenzae type b
      tetanus toxoid vaccine (PRP-T) so that infants received a single injection at age
      2, 3 and 4 months. One month after the third dose the geometric mean titre of Hib
      IgG antibody was 0.48 microgram ml-1. Eighty-two percent of infants achieved a
      titre of 0.15 microgram ml-1, with only 27% achieving 1.0 microgram ml-1. This
      combination vaccine induced low Hib antibody responses when compared to other
      studies in which PRP-T was mixed with acellular or whole-cell pertussis vaccines.
      The combined vaccine did, however, appear to prime a subset of 35 infants for
      response to a fourth dose of PRP-T at 13 months of age, with a rise in GMT from
      0.21 microgram ml-1 to 36.6 micrograms ml-1. These data have important
      implications for the introduction of combination acellular pertussis vaccines.

PMID- 9569477
TI  - Immunogenicity of hepatitis B vaccines among infant recipients of acellular and
      whole cell pertussis DTP vaccines.
AB  - The study was conducted to assess the immunogenicity of three doses of two
      recombinant hepatitis B virus (HBV) vaccines, administered simultaneously with a
      DT vaccine or one of three different pertussis vaccines combined with diphtheria
      and tetanus toxoids. The study population consisted of 1237 children selected
      from the cohort of 15,601 children enrolled in the Italian trial on pertussis
      vaccines. HBV vaccination was performed at 2, 4 and 12 months of age, with the
      first two doses concurrent with OPV and DTP vaccination. The DTP vaccines
      administered in the pertussis trial included one whole cell DTP, licensed in the
      USA, and two three-component acellular DTaPs, manufactured in Europe.
      Immunogenicity to HBV was evaluated on serum samples collected 9 months after the
      third dose of HBV vaccine. Antibodies against HBsAg were detected by ELISA and
      expressed in mlU/ml. In 13 children, the antibody response was below the
      protective level of 10 mlU/ml-1. No statistical difference was found among the
      various study groups with respect to the proportion of children showing
      protective response. Higher humoral response was observed in children receiving
      mixed HBV vaccines in each pertussis study groups.

PMID- 9569478
TI  - Adverse impact of infections on antibody responses to measles vaccination.
AB  - Antibody titres were determined in 102 Thai infants who were vaccinated at 9
      months of age during the respiratory disease season. The symptom densities of
      illnesses at or following vaccination, including rhinorrhea and diarrhea, were
      significantly lower among seroconverters, although the simple presence or absence
      of specific symptoms was not significantly related to seroconversions. Logistic
      regression indicated that neutralization test antibody titres below the median
      titre of 1:80 following vaccination were significantly more frequent among those
      with rhinorrhea when vaccinated and among those with diarrhea after vaccination.
      Compared with a referent group without these symptoms, titres were lower in those
      who had rhinorrhea when vaccinated, rhinorrhea during the first week post
      vaccination, and diarrhea in either of the two follow-up weeks. Illnesses
      concurrent or subsequent to measles vaccination adversely affected antibody
      responses in these study objects.

PMID- 9569479
TI  - Pre-transport loading of farmed red deer: effects of previous overnight housing
      environment, vehicle illumination and shape of loading race.
AB  - The behaviour of farmed red deer was studied while they were being loaded on to a
      transporter. In experiment 1, the effects of previous overnight housing
      conditions (indoors, at a space allowance of either 4 or 8 m2 per deer, or in an
      outdoor raceway) on the ease of loading were investigated. The number of attempts
      required to load the deer was not significantly affected by their housing
      conditions or their sex, but there was a significant increase in the number of
      attempts required after the first day (P < 0.05), suggesting that some aspect of
      the loading procedure was aversive to the deer. In experiment 2, the effects of
      illumination inside the vehicle (bright or dim) and the shape of the loading race
      (straight or curved) were examined. Neither factor significantly influenced the
      time taken by deer to enter the trailer. However, deer took significantly (P <
      0.05) less time to load as the number of trials increased. It is concluded that
      the loading of deer may be facilitated if the loading raceway is wide enough to
      allow the deer to move as a group, but narrow enough to prevent the deer from
      turning round.

PMID- 9569480
TI  - Elimination of mucosal cyathostome larvae by five daily treatments with
      fenbendazole.
AB  - The efficacy of five daily treatments with 7.5 mg fenbendazole/kg bodyweight
      against mucosal cyathostome larvae was evaluated in 20 12- and 24-month-old
      ponies with naturally acquired cyathostome infections. After three weeks communal
      grazing on infected pasture and six weeks indoors, one group of 10 ponies were
      treated. Six weeks later, both groups of ponies were humanely destroyed and their
      burdens of large intestinal cyathostome worms, including luminal parasites and
      mucosal larvae, were assessed. In the control animals approximately 7 per cent of
      the total worm burden was present in the gut lumen and 93 per cent was present as
      larvae in the large intestinal mucosa. The efficacy of fenbendazole against the
      luminal cyathostomes was 90.7 per cent (P < 0.01). The total numbers of mucosal
      larvae, recovered after digestion, were reduced by 95.3 per cent (P < 0.0005);
      mucosal late third and fourth stage larvae were reduced by 99.4 per cent (P <
      0.0001), and early inhibited third stage larvae by 91.5 per cent (P < 0.005).

PMID- 9569481
TI  - Use of ultrasonography to help to predict observed oestrus in dairy cows after
      the administration of prostaglandin F2 alpha.
AB  - A total of 76 cows from seven herds with an ultrasonographically visible corpus
      luteum at routine herd fertility examinations were treated with prostaglandin F2
      alpha. The sizes of the cavities of all the follicles on both ovaries with a
      diameter greater than 5 mm were measured. The cows were observed for signs of
      oestrus over the following six days and the time to onset of oestrus was
      recorded. Milk samples collected when the prostaglandin was administered and at
      oestrus were assayed for milk progesterone concentration. The herd of origin,
      lactation number, body condition score, days after calving at the time of
      examination and the total number of follicles when the prostaglandin was
      administered were not found to have any correlation with time to oestrus. Seventy
      three of the 76 cows had milk progesterone concentrations consistent with active
      luteal tissue when the prostaglandin was administered, and 33 of them were
      observed in oestrus and had low milk progesterone concentration within six days.
      The mean time to the onset of oestrus was significantly and inversely related to
      the size of the cavity of the smallest follicle with a diameter of more than 5
      mm.

PMID- 9569482
TI  - A retrospective study of mortality associated with general anaesthesia in horses:
      elective procedures.
AB  - A retrospective analysis examined mortality associated with all procedures
      requiring general anaesthetic, performed at the Philip Leverhulme Large Animal
      Teaching Hospital, during the five-year period from February 1991 to December
      1995. The study involved details relating to 2276 equine general anaesthetics and
      a variety of patient variables were examined. Within a group of 1279 animals
      undergoing anaesthesia for elective procedures, 46 (3.6 per cent) died or were
      euthanased owing to a poor prognosis or financial implications. Mortality
      relating directly to the surgery or anaesthesia occurred in eight of these cases.
      Therefore, the surgical/anaesthetic death rate was 0.63 per cent. Death which was
      apparently attributable directly to the anaesthesia (no organic cause of death
      found at postmortem examination) occurred only once, giving an anaesthetic death
      rate of 0.08 per cent.

PMID- 9569483
TI  - Abattoir survey of sheep and goats in The Gambia.
AB  - An abattoir survey of sheep and goats was carried out in The Gambia for one year.
      A total of 1248 goats and 438 sheep, predominantly young females, were
      slaughtered and sampled. Sixty per cent of the females of both species were
      pregnant. There were no significant differences between the dressing percentages
      of different breeds and age groups. Sex and stage of pregnancy had a significant
      influence on carcase yields in both species. In goats the highest carcase yields
      were obtained during the early dry season. Most of the animals were clinically
      healthy and there were few pathological findings postmortem. In both species,
      there was a seasonal fluctuation of packed cell volume (PCV), with a minimum
      during the rains, and although the prevalence of trypanosomiasis was low it
      reduced the PCV. Faecal egg counts of Trichostrongylidae were highest during the
      rainy season and goats had higher faecal egg and coccidial oocyst counts than
      sheep. In sheep, a breed difference was observed for PCV and an age difference
      for egg excretion. The peak or higher rates of egg excretion occurred during the
      rains in both species. The immune status against peste des petits ruminants was
      significantly lower in goats (39 per cent) than in sheep (49.5 per cent).
      Antibodies against bluetongue virus were found in 62.6 per cent of goats and 55.8
      per cent of sheep.

PMID- 9569484
TI  - Cattle and verotoxigenic Escherichia coli (VTEC), an old relationship?

PMID- 9569485
TI  - Cryotherapy for canker in a horse.

PMID- 9569486
TI  - Changes to the Veterinary Laboratories Agency.

PMID- 9569487
TI  - Severe udder oedema and teat necrosis in related dairy heifers.

PMID- 9569488
TI  - Ciprofloxacin-resistant Salmonella typhimurium DT104.

PMID- 9569489
TI  - Cryptosporidiosis in young alpacas.

PMID- 9569490
TI  - Neutering and longevity in dogs.

PMID- 9569491
TI  - Use of the flexion test in horses.

PMID- 9569492
TI  - Bone and BSE.

PMID- 9569493
TI  - 'Twitchiness' in miniature wirehaired dachshunds.

PMID- 9569494
TI  - [Simvastatin inhibits coronary heart disease progression and prolongs life
      expectancy].

PMID- 9569496
TI  - Intracardiac overdrive pacing as a treatment of atrial flutter in a horse.
AB  - A five-year-old warmblood mare with atrial fibrillation was treated with
      quinidine sulphate. The atrial rhythm changed to atrial flutter and, because
      there were toxic effects, the treatment was discontinued. Seven months after the
      occurrence of the atrial flutter, treatment with a rapid atrial pacing technique
      restored a normal sinus rhythm. One year after the pacing therapy the horse was
      still in sinus rhythm and had been brought back into training.

PMID- 9569495
TI  - Mycobacterial antigen-specific antibody responses in bovine tuberculosis: an
      ELISA with potential to confirm disease status.
AB  - Serological assays may help to identify animals in advanced stages of bovine
      tuberculosis, but most of the tests available have suboptimal sensitivities and
      specificities. This study was designed to determine whether the antibody
      responses to defined antigens (rMPB70, rMPB64 and rMPB59) of Mycobacterium bovis
      at the immunoglobulin subclass level could be used to develop improved
      serological tests. In experimentally infected cattle it was found that the
      predominant serum antibody response was to rMPB70, and that an IgG1 response to
      this antigen was boosted strongly by skin testing. Studies in naturally infected
      cattle suggested that this memory IgG1 anti-rMPB70 response may be able to
      differentiate between skin test-reactor animals with and without lesions by
      comparing the ratio of the antibody response before and after skin testing. The
      study has provided a clearer understanding of the kinetics of antibody responses
      to defined mycobacterial antigens at the subclass level in bovine tuberculosis
      and has made it possible to develop a novel ELISA system which may be useful in
      disease diagnosis.

PMID- 9569497
TI  - Evaluation of false ultrasonographic diagnoses in cows by measuring plasma levels
      of bovine pregnancy-associated glycoprotein 1.
AB  - Between days 27 and 59 after artificial insemination (AI), 189 ultrasonographic
      pregnancy diagnoses were made in 56 dairy cows using a 7.5 MHz linear-array
      rectal transducer. Blood samples were withdrawn from a jugular vein on the day of
      AI, on day 21, and after each ultrasonographic examination between days 27 and
      31, days 34 and 38, days 41 and 45 and days 55 and 59 after AI. Plasma
      concentrations of bovine pregnancy-associated glycoprotein 1 (bPAG-1) were
      measured by radioimmunoassay. The results showed that before day 31,
      ultrasonographic scanning was not very sensitive because six of the 30 calving
      cows were incorrectly diagnosed as non-pregnant. In five of these animals, the
      uterus was located far cranial to the pelvic inlet. Five of the cows examined
      between days 27 and 31 were pregnant on the basis of plasma bPAG-1 levels on the
      same day, using 0.5 ng/ml as the cut-off point. Plasma levels of bPAG-1 and
      progesterone proved that four of the cows which had early positive
      ultrasonographic diagnoses but did not produce a calf, were pregnant when they
      were examined.

PMID- 9569498
TI  - A retrospective study of mortality associated with general anaesthesia in horses:
      emergency procedures.
AB  - A retrospective study evaluated 995 emergency equine general anaesthetics. The
      total mortality for emergency procedures was 31.4 per cent. This figure was
      examined in more detail to determine if all emergency procedures carried a
      similar risk. Horses anaesthetised for surgical colic had an increased risk of
      death or euthanasia, with a total mortality of 35.5 per cent when compared to
      horses anaesthetised for non-colic related problems which had a total mortality
      of 15.3 per cent. The findings of this study illustrate the greatly increased
      risk of mortality in horses undergoing general anaesthesia for emergency
      procedures. Mortality is 4.25 times more likely for emergency procedures not
      associated with colic than for similar procedures carried out electively.
      Emergency general anaesthesia for colic carries an increased risk of mortality of
      9.86 times that of elective cases.

PMID- 9569499
TI  - Feral pigeons as a source of verocytotoxin-producing Escherichia coli.

PMID- 9569500
TI  - Dermatitis caused by Malassezia pachydermatis in a California sea lion (Zalophus
      californianus).

PMID- 9569501
TI  - Use of the flexion test in the pre-purchase examination of horses.

PMID- 9569502
TI  - Use of monensin in sheep feeds.

PMID- 9569503
TI  - Booster intervals for feline vaccines.

PMID- 9569504
TI  - Vaccination, health checks and the 24-hours service.

PMID- 9569505
TI  - Delegation of tasks to veterinary nurses.

PMID- 9569506
TI  - Delegation of tasks to veterinary nurses.

PMID- 9569508
TI  - Veterinary care of racing pigeons.

PMID- 9569507
TI  - Stairs and foreleg lameness in dogs.

PMID- 9569509
TI  - Foot trimming in cattle.

PMID- 9569510
TI  - Blood testing chinchillas.

PMID- 9569511
TI  - The quality of the body cell mass--1996. Are we ready to measure it?

PMID- 9569512
TI  - Trace element concentrations studied in vivo using X-ray fluorescence analysis.

PMID- 9569513
TI  - Bioimpedance spectrometry in the determination of body water compartments:
      accuracy and clinical significance.
AB  - Bioelectrical impedance analysis (BIA) offers the potential for a simple,
      portable and relatively inexpensive technique for the in vivo measurement of
      total body water (TBW). The potential of BIA as a technique of body composition
      analysis is even greater when one considers that body water can be used as a
      surrogate measure of lean body mass. However, BIA has not found universal
      acceptance even with the introduction of multi-frequency BIA (MFBIA) which,
      potentially, may improve the predictive accuracy of the measurement. There are a
      number of reasons for this lack of acceptance, although perhaps the major reason
      is that no single algorithm has been developed which can be applied to all
      subject groups. This may be due, in part, to the commonly used wrist-to-ankle
      protocol which is not indicated by the basic theory of bioimpedance, where the
      body is considered as five interconnecting cylinders. Several workers have
      suggested the use of segmental BIA measurements to provide a protocol more in
      keeping with basic theory. However, there are other difficulties associated with
      the application of BIA, such as effects of hydration and ion status, posture and
      fluid distribution. A further putative advantage of MFBIA is the independent
      assessment not only of TBW but also of the extracellular fluid volume (ECW),
      hence heralding the possibility of being able to assess the fluid distribution
      between these compartments. Results of studies in this area have been, to date,
      mixed. Whereas strong relationships of impedance values at low frequencies with
      ECW, and at high frequencies with TBW, have been reported, changes in impedance
      are not always well correlated with changes in the size of the fluid compartments
      (assessed by alternative and more direct means) in pathological conditions.
      Furthermore, the theoretical advantages of Cole-Cole modelling over selected
      frequency prediction have not always been apparent. This review will consider the
      principles, methodology and applications of BIA. The principles and methodology
      will be considered in relation to the basic theory of BIA and difficulties
      experienced in its application. The relative merits of single and multiple
      frequency BIA will be addressed, with particular attention to the latter's role
      in the assessment of compartmental fluid volumes.

PMID- 9569514
TI  - Comparisons between fat measurements by dual-energy X-ray absorptiometry,
      magnetic resonance imaging and underwater weighing.

PMID- 9569516
TI  - Measurement and prediction of total body fat.
AB  - Though it has been established that skinfold anthropometry has severe limitations
      as a method of deriving total body fat (TBF), the possibility that the problem
      might be related more to the assumptions implicit in densitometry has to be
      addressed. This paper suggests that smaller residual errors might be obtained if
      sums of skinfolds are regressed against TBF measured by a difference technique
      (IVNAA + 3H2O dilution), suggesting that the latter may perhaps be a better
      standard than densitometry.

PMID- 9569515
TI  - Body fat: estimation or guesstimation?
AB  - Skinfold anthropometry is performed world-wide with little appreciation of its
      limitations. This paper shows that it is important to appreciate the magnitude of
      the biological component of the residual error in any regression of body density
      against sums of skinfolds; for example, for young adult males a biological error
      of around 21% (s.d.) is observed. Such 'errors' simply express nature's refusal
      to conform to imposed regression relationships, reflecting the inherent
      variability in the ratio of subcutaneous to total body fat.

PMID- 9569518
TI  - Effect of temperature and sweating on bioimpedance measurements.
AB  - The effect of skin temperature and hydration status has been suggested by some
      researchers as a common cause of variation in bioimpedance measurements of the
      body. This paper details a simple method of measuring the transverse impedance of
      the skin. The measured resistance and reactance was found to decrease by 35% and
      18% for an increase of 20 degrees C. Similarly a decrease in resistance and
      reactance of 20% and 25% respectively was detected after hydration of the skin.
      However, the changes in skin temperature and hydration were found to have no
      significant effect on the whole body bioimpedance measurements using the standard
      tetra-polar electrode technique.

PMID- 9569517
TI  - A comparison of different methods to measure body composition in patients.
AB  - A comparison of different methods to measure body composition in growth hormone
      deficient patients is presented. The technical limitations of the available
      methods are discussed. The techniques used to measure body composition and fat
      free mass has been by total body water, total body potassium, dual energy X-ray
      absorptiometry, bioelectrical impedance and total body nitrogen.

PMID- 9569519
TI  - A comparison of segmental and wrist-to-ankle methodologies of bioimpedance
      analysis.
AB  - The common approach of bioelectrical impedance analysis to estimate body water
      uses a wrist-to-ankle methodology which, although not indicated by theory, has
      the advantage of ease of application particularly for clinical studies involving
      patients with debilitating diseases. A number of authors have suggested the use
      of a segmental protocol in which the impedances of the trunk and limbs are
      measured separately to provide a methodology more in keeping with basic theory.
      The segmental protocol has not, however, been generally adopted, partly because
      of the increased complexity involved in its application, and partly because
      studies comparing the two methodologies have not clearly demonstrated a
      significant improvement from the segmental methodology. We have conducted a small
      pilot study involving ten subjects to investigate the efficacy of the two
      methodologies in a group of normal subjects. The study did not require the
      independent measure of body water, by for example isotope dilution, as the
      subjects were maintained in a state of constant hydration with only the
      distribution between limbs and trunk changing as a result of change in posture.
      The results demonstrate a significant difference between the two methodologies in
      predicting the expected constancy of body water in this study, with the segmental
      methodology indicating a mean percentage change in extracellular water of -2.2%,
      which was not significantly different from the expected null result, whereas the
      wrist-to-ankle methodology indicated a mean percentage change in extracellular
      water of -6.6%. This is significantly different from the null result, and from
      the value obtained from the segmental methodology (p = 0.006). Similar results
      were obtained using estimates of total body water from the two methodologies.

PMID- 9569520
TI  - A comparison of two multi-frequency bioimpedance analysers.

PMID- 9569521
TI  - Evaluation of multifrequency bioimpedance spectroscopy for measurement of the
      extracellular water space in critically ill patients.
AB  - The purpose of this study was to compare multifrequency bioimpedance spectroscopy
      (BIS) estimates of extracellular water volume (ECW) in critically ill patients
      with measurements by bromide dilution. Stable bromide dilution and BIS were
      performed in 37 critically ill patients as soon as haemodynamic stability was
      achieved (day 0) and again 10 days later. While BIS underestimated the dilution
      results on each day of measurement, the 10-day changes in ECW agreed closely for
      the two methods (4.42 +/- 4.25 (s.d.) vs 4.43 +/- 4.84 1).

PMID- 9569522
TI  - Factors affecting the in vivo precision of bioelectrical impedance analysis.
AB  - The influence of factors which affect the in vivo precision of bioelectrical
      impedance measurements was investigated in two young female volunteers. Measured
      impedance increased consistently with time with the subject lying supine,
      although the effect could be eliminated by rising between measurements. Electrode
      placement had a relatively large effect, while moving the electrodes such that
      the volume of conducting tissue was reduced caused the impedance to decrease.
      Cleaning the skin with alcohol, moving the arm away from the body, and eating a
      large meal caused impedance to increase systematically. However, drinking a litre
      of water and varying the depth of respiration had no observable effect.

PMID- 9569523
TI  - Phase angle spectrum analysis and body water.

PMID- 9569524
TI  - Total body capacity correlated with basal metabolic rate.
AB  - This study was conducted to establish the relationship between a new
      bioelectrical parameter, total body capacitance (TBpF), as an expression of body
      cell mass, measured using an impedance analyser and basal metabolic rate (BMR),
      by indirect calorimetry in 75 healthy subjects (38 females and 37 males, aged
      between 13 y and 43 y). A significant high correlation was found between TBpF and
      BMR (r = 0.992, SEE = 238 kcal) with the equation: BMR (kcal day-1) = Capacity
      (pF) x 2.29.

PMID- 9569525
TI  - Hydration status assessed by multi-frequency bioimpedance analysis.

PMID- 9569526
TI  - Relevance of hydration state of the fat free mass in estimating fat mass by body
      impedance analysis.
AB  - Body impedance analysis (BIA) is widely used to assess body composition, however,
      accurate estimates of fat mass (FM) are sometimes rendered impossible due to over
      or dehydration states. In fact, BIA is accurate in total body water (TBW)
      estimates, and TBW can be converted into fat free mass (FFM) assuming 73%
      hydration; but, if there is an alteration in the hydration state, such a fixed
      value does not fit with the real content of fluids in the FFM compartment, thus
      causing wrong estimates of FFM and in turn of FM. For this reason, phase
      sensitive bioelectric analyzers operating at a single frequency or at multiple
      frequencies have recently been under investigation in order to produce an
      equation that is also able to estimate the volume of extracellular water (ECW).
      Some authors, rather than trying to find the best equation or the best instrument
      approach, have tested the direct use of resistance, reactance and phase angle
      values derived from 50 kHz impedance measurements, assuming that normal
      bioelectrical values are associated with normal hydration states. Using a large
      series of data we have found strong correlations between BIA-derived FM and BMI,
      and our data show that screening the subjects with normal hydration states using
      the direct bioelectrical parameters (BIAGRAM) improves the predictivity of
      standard equations, since it avoids trying to estimate FM in overhydrated
      subjects.

PMID- 9569527
TI  - Precision of body composition measurements by dual energy X-ray absorptiometry.

PMID- 9569528
TI  - Whole-body phantoms with anthropomorphic-shaped skeletons for evaluation of dual
      energy X-ray absorptiometry measurements.
AB  - We have developed a set of four whole-body phantoms with anthropometric-shaped
      skeletons constructed of CaHPO4-doped epoxy resin, to simulate average body sizes
      of children at ages 4, 10, 15, and 18. Each phantom was measured on a Hologic QDR
      2000 instrument with and without a set of polyethylene overlays to simulate
      excess body fat, and with and without a 0.6% NaCl/water mixture to simulate
      differences in lean tissue composition. Precision of total body BMC, based on 4
      scans over 2 wk, were 0.5%-1.8%, and were correlated (r2 = 0.999, p < 0.001) with
      the chemical Ca content of the simulated skeleton. The addition of overlays to
      the phantoms to simulate increased body size and/or body fat resulted in small
      but significant increases in the measured values for BMC and bone area, but not
      that of BMD.

PMID- 9569529
TI  - Changes in body fat: measurements by neutron activation, densitometry and dual
      energy X-ray absorptiometry.
AB  - The measurement of body fat in ten subjects (BMI from 22 to 43 kg/m2), and in
      particular the changes arising from a ketogenic diet, by the techniques of in
      vivo neutron activation analysis (NAA), densitometry (using two- and four
      compartment models) by under water weighing (UWW) and dual energy X-ray
      absorptiometry (DXA) was compared. The association between techniques for the fat
      changes was generally high (r = 0.70 to 0.98) and significant (p < 0.05).
      Assessment of agreement between DXA and the other techniques revealed
      discrepancies with significant slope and high association (r = -0.81 and -0.64).
      Whilst NAA and UWW appeared to measure similar changes, DXA underestimated small
      changes.

PMID- 9569530
TI  - DXA body composition: theory and practice.
AB  - Dual energy X-ray absorptiometry (DXA) was used to measure human body composition
      on a high speed fan beam scanner. High and low energy attenuation pairs, produced
      by the various combinations of fat mass and fat-free mass in the human body, were
      compared to attenuation values produced by standard materials (aluminum and
      acrylic). These standards were measured in various combinations to construct
      calibration curves for fat and fat-free mass. Primary calibration of the
      aluminum/acrylic combinations was achieved by direct comparison to the dual
      energy attenuation produced by stearic acid and pure water. Whole body
      examinations were accomplished using three 45 s longitudinal passes of the fan
      beam. These passes were acquired and assembled to create a giant, isocentric fan
      beam with a single center of focus. In vivo precision was 0.009 g/cm2 for BMD and
      425 g for fat mass and fat-free mass (s.d.).

PMID- 9569531
TI  - Body composition results by DXA differ with manufacturer, instrument generation
      and software version.

PMID- 9569532
TI  - Body composition analysis of pigs from 5 to 97 kg by dual energy X-ray
      absorptiometry.
AB  - A total of 231 pigs were anesthetized and then scanned by DXA using a Lunar DPXL
      instrument. The weight of the pigs ranged from 5 to 97 kg (av. = 37.7 kg). Of the
      total, 98 pigs were scanned using the pediatric mode and 133 pigs were scanned
      using the adult mode. After scanning, the pigs were euthanized, the entire body
      homogenized by grinding, and analyzed chemically for fat, water, protein and
      total body mineral content. The mean value for the DXA total tissue mass (37.1
      kg) was not significantly (P > 0.05, n = 231) different from the mean body
      weight. The mean DXA value for percent fat was 14.6 and was significantly less (P
      < 0.05) than the mean value (17.6%) measured by CHEM analysis. The greatest
      discrepancy occurred in pigs with < 15% body fat. From a prediction equation
      using the DXA R value [% fat = 493-349(DXA R value)], the DXA estimated percent
      fat was 18.0%, compared to 17.6% by CHEM analysis (P > 0.05). Using a prediction
      equation [g protein = -1.062 + 0.22(g DXA lean)], the DXA estimate for body
      protein content was 17.8%, compared to 17.1% (P < 0.05, n = 131) by CHEM
      analysis. The DXA estimate for body water content [g water = 508 + 0.74 (g DXA
      lean)] was 63.8%, compared to 62.6% (P < 0.05, n = 231) by CHEM analysis. The
      bone mineral content of 83 of the pigs measured by DXA was 2.40%, compared to
      2.54% (P < 0.05, n = 83) estimated from CHEM analysis of total body ash [g bone
      mineral = g total body ash -0.0085(g DXA lean)].

PMID- 9569533
TI  - Comparison of in vivo body composition using two Lunar dual-energy X-ray
      absorptiometers.

PMID- 9569534
TI  - Multi-frequency bio-electrical impedance: precision in normal children.

PMID- 9569535
TI  - Body-size corrections for in vivo neutron activation analysis.
AB  - Differences in body size and shape can cause large variances in the results of in
      vivo neutron activation analysis. Preliminary body-size correction data were
      obtained for the delayed-gamma neutron activation facility (DGNA) at Brookhaven
      National Laboratory (BNL), based on phantom standards of different sizes, used in
      combination with computer simulations on the effect of different body sizes.

PMID- 9569536
TI  - Total body chlorine: calibration of the in vivo neutron activation measurement.
AB  - Total body chlorine (TBCI), used to estimate the extracellular space, is measured
      by delayed-gamma neutron activation (DGNA) using the reaction 37Cl(n, gamma)38Cl,
      at Brookhaven National Laboratory. During the calibration process, we noticed
      that different values were obtained when different amounts of Cl were placed in
      the phantom. This non-linear relationship is due to the thermal neutron flux
      suppression by the thermal neutron capture reaction 35Cl(n, gamma)36Cl. Monte
      Carlo simulations confirm the results of phantom measurements showing an inverse
      relationship between the Cl content in the phantom and the gamma-ray yield per
      gram Cl. Thus, it is important to calibrate the DGNA system for TBCl using
      phantom standards containing an amount of Cl close to that expected in the
      individual undergoing measurement.

PMID- 9569537
TI  - Calibration of a prototype in vivo total body composition analyser using 14 MeV
      neutron activation and the associated particle technique.
AB  - A prototype in vivo total body composition analyser has been constructed for
      determining the total body contents of nitrogen (TBN), carbon (TBC) and oxygen
      (TBO) in young experimental animals such as sheep or pigs by 14 MeV neutron
      activation using a commercially available associated particle sealed tube neutron
      generator (APSTNG). The instrument was calibrated by scanning phantoms of
      different sizes in the mass range 10-36 kg, filled with a mixture of elements as
      found in a normal human body. Good agreement was found between the measured and
      expected values of N, O and C when two phantoms of similar dimensions but of
      different composition were scanned. With four 15 cm x 15 cm cross section and 45
      cm long NaI(T1) gamma detectors and a radiation dose of approximately 20 microSv
      due to neutrons, the expected precisions for a 28 kg animal, CV% (based on
      counting statistics) are N: 9.3, C: 2.3 and O: 1.4.

PMID- 9569538
TI  - Monte Carlo simulation of prompt gamma neutron activation analysis using MCNP
      code.
AB  - Prompt gamma neutron activation analysis (PGNAA) is the most direct method of
      measuring total-body nitrogen. In combination with internal hydrogen
      standardisation, it is possible to reduce the dependence on body habitus. The
      uniformity of activation and detection, however, cannot be optimised sufficiently
      to eliminate the dependence entirely, and so further corrections are essential.
      The availability of the powerful Monte Carlo code MCNP(4A) has allowed a more
      accurate analysis of the activation facility, and yields corrections for body
      habitus and superficial fat layers. The accuracy of the correction is retained as
      the source-to-skin distance is reduced, although the activation uniformity is
      thereby degraded. This allows the use of a 252Cf source with lower activity and
      hence reduces the running cost of the facility.

PMID- 9569539
TI  - The elemental analysis of the human body using associated particle timing based
      on the D + D reaction.
AB  - Fast (approximately 2.8 MeV) neutrons are generated in the 2H(d,n)3He reaction,
      and are used for excitation of sample materials via inelastic scattering.
      Nanosecond timing identifies the spatial origin of the measured gamma radiation,
      making possible three-dimensional imaging and improved detection sensitivity.
      Several elements have been measured, and it is estimated that a clinical device,
      with equivalent dose of 10 mSv, will be capable of detecting the order of 10-100
      mg.

PMID- 9569540
TI  - Prospects of imaging by associated particle timing with D + D and D + T neutrons.
AB  - The optimum parameters and limits are predicted for the performance of an
      associated particle imaging system on the basis of recently completed projects
      studying the use of timing with neutrons for elemental analysis of bulk samples
      such as the human body or traveling trunks.

PMID- 9569541
TI  - Gamma-ray backscatter for body composition measurement.
AB  - The purpose of this study was to examine the potential of using backscatter
      information to assess regional body composition at selected sites. Two
      measurement techniques are examined: the measurement of the ratio of coherent to
      Compton scatter, and the measurement of the Compton scatter profile. Two possible
      applications are considered: the measurement of trabecular bone mineral density,
      and the measurement of the average fat/muscle ratio in a tissue volume. The
      results presented indicate that the analysis of coherent and Compton
      backscattered gamma-ray spectra from an 241Am source has the potential for
      measuring both trabecular bone mineral density and average fat/muscle ratio in a
      tissue volume, with a low absorbed dose to the subject.

PMID- 9569542
TI  - Dose reduction for body composition measurements with CT.
AB  - The purpose was to obtain reliable measures of fat and muscle tissue areas with
      CT at a reduced radiation dose level. Repeated CT-scans with four different
      levels of reduced radiation dose were perfomed on a water phantom and a volunteer
      at the L4-L5 level. Dose measurements were performed in a phantom and free in
      air. A histogram model function for fat, muscle and partial volume affected
      voxels was proposed and used in the analysis of image noise. The result was at
      most a 25-fold reduction in radiation dose with an image noise of 40 HU but only
      a minor influence on the tissue area determination [corrected].

PMID- 9569543
TI  - The use of computed microtomography to monitor morphological changes in small
      animals.
AB  - RATIONALE AND OBJECTIVES: We investigate the methodological aspects of
      computerised microtomography (Cm 1) for monitoring the development of
      osteoporosis in male Sprague-Dawley rats. METHODS: 120 Rats were gastrectomized
      or sham operated. Femurs were prepared and tomograms with spatial resolutions of
      5-500 mm were made. Bone diameters, bone areas and moments of inertia were
      determined from the tomograms. Optimal slice position and the need for spatial
      resolution for future in vivo applications were investigated. In order to
      minimise the absorbed dose to the specimen, a theoretical model for determination
      of optimal irradiation conditions is developed. RESULTS: Gastrectomy caused
      dramatic changes in the bone architecture. The main features were vaccuolisation
      of the bone and reduced amounts of compact bone. While the outer diameters of
      tubular bones were largely unaffected, their inner diameters were greatly
      increased following gastrectomy. Relative bone area and moment of inertia were
      greatly reduced. Optimal photon energy was 12 keV. CONCLUSIONS: It is possible to
      monitor gastrectomy-evoked changes in bone morphology at various sites in rats
      with computerised microtomography. The changes are suggestive of osteoporosis.

PMID- 9569544
TI  - Longitudinal changes in adult body composition: influence of body weight.

PMID- 9569545
TI  - Exercise and body composition revisited: the effect of body weight change.

PMID- 9569546
TI  - Changes in body composition during growth in healthy school-age children.
AB  - Bone-mineral-free lean body mass (LBM) and fat mass (FM) were determined by DXA
      scanning in 343 healthy children and adolescents (142 males) aged 4.9-19.3 yr.
      The main sex difference was the earlier flattening of the LBM according to age
      curve for girls compared to boys and the higher increase in FM with age in girls.
      332 persons (140 males) were examined again after 1 yr and accretion rates for
      LBM and FM were calculated. The main sex difference was a later and higher peak
      in LBM accretion in boys compared to girls and a nearly constant increase in FM
      throughout puberty in girls, while boys had no increase in FM during puberty. The
      differences may reflect the higher androgen production in male puberty.

PMID- 9569547
TI  - Age- and maturity-related changes in body composition during adolescence into
      adulthood: the Fels longitudinal study.
AB  - We examined patterns of change in body composition from 8 to 20 yrs of age and
      the effects of rate of maturation on these patterns using serial data for total
      body fat (TBF). There is a continual increase, but a declining rate of change
      with age in TBF. For %BF the same pattern as for TBF exists for females, but for
      males the pattern of change in percentage body fat (%BF) reflects the concurrent
      changes in fat free mass (FFM). For FFM, there is an increase in females that
      slows at older ages, but in males there is a continual rapid increase until young
      adulthood. There is marked tracking for body composition persisting from
      childhood to adulthood. At the same age, rapidly maturing children have
      significantly larger TBF, %BF and FFM than slowly maturing children.

PMID- 9569548
TI  - Body composition reference data for a young multiethnic female population.

PMID- 9569549
TI  - Age related changes in body composition.

PMID- 9569550
TI  - Assessment of body composition of children with cystic fibrosis (CF).

PMID- 9569551
TI  - Volumetric bone mineral density in children with cystic fibrosis.

PMID- 9569552
TI  - Correlation between skeletal calcium mass and muscle mass in man revisited: age,
      gender, and ethnicity.

PMID- 9569553
TI  - Evaluation of modified multicompartment models to calculate body composition in
      healthy males.
AB  - Body volume was measured by underwater weighing (UWW) or with a skinfold caliper;
      bone mineral by dual energy X-ray absorptiometry (DXA); and body water by
      bioelectrical impedance analysis (BIA) in 22 healthy males. The percentage of
      water and bone mineral in fat-free mass had a significant effect on the
      calculated amount of fat using a two-compartment model. A three-compartment model
      based on field-adapted methods (skinfold thickness + BIA) to calculate body fat,
      correlated significantly with a more complex four-compartment model (UWW + BIA +
      DXA) (r = 0.95, p < 0.001). The advantages of three- and four-compartment
      equations are that they reduce the number of assumptions.

PMID- 9569554
TI  - Total body oxygen: assessment from body weight and total body water.

PMID- 9569555
TI  - The use of bioimpedance spectroscopy to monitor water changes induced by
      rehydration in young children with abnormal water disturbances associated with
      diarrheal disease.

PMID- 9569556
TI  - Bioelectrical impedance spectroscopy (BIS) in young children with acute and semi
      acute hydration disorders: potentials and limitations.
AB  - This study aimed to evaluate the feasibility and reliability of bioelectrical
      impedance spectroscopy in young children suffering of acute hydrational
      disorders. Whole body and segmental measurements were carried out in a group of
      42 of children aged 4 to 147 months, using a BIS analyzer (Xitron 4000B). This
      phase of the study involved several hundred of BIS measurement, which showed the
      feasibility of using this technique in young children. Using the sweep mode and
      the modeling software provided for the manufacturer of the instrument, the
      resistance of the extracellular (RECW) and intracellular (RICW) compartment was
      calculated. Correlation coefficient (r) and technical error of measurement (TEM)
      were obtained from paired BIS measurements. RECW showed to be highly reproducible
      (r = 0.99), with a relatively low TEM (from 1 to 3.5%), across all segments. The
      reliability was markedly lower respect to RICW, which shows the potential
      application of BIS technique even in critically ill young child populations.

PMID- 9569557
TI  - Monitoring of fluid changes in hospitalized, Malnourished, Guatemalan children
      using bioelectrical impedance spectroscopy (BIS).

PMID- 9569558
TI  - Use of bioelectric impedance analysis (BIA) in children with alterations of body
      water distribution.
AB  - Validation studies of bioelectric impedance analysis (BIA) were performed in
      children with obesity, Duchenne muscle dystrophy and juvenile rheumatoid
      arthritis. BIA allowed an accurate assessment of total body water in all groups
      (CV from 4.1 to 5.1%). However, the prediction of extracellular water by BIA was
      not always satisfactory (CV from 8.5 to 12.5%), being better in the groups of
      children with the lowest variability in body water distribution.

PMID- 9569559
TI  - Comparison of dual-energy X-ray absorptiometry and four-component model estimates
      of body fat in American Indian men.

PMID- 9569560
TI  - A pilot study to measure changes in body composition in very obese women on
      hypocaloric diets.

PMID- 9569561
TI  - Studies on electrolyte and trace metal metabolism applying stable isotopes as
      tracers.
AB  - Tracer-kinetic investigations provide a useful tool for the assessment of body
      composition regarding electrolytes and trace elements. This paper demonstrates
      the feasibility of stable isotopes as tracers in studies on calcium and iron
      metabolism in risk groups like children. By applying both radioisotopes and
      stable isotopes simultaneously, in adults, a good intra-individual agreement was
      obtained for the derived figures of intestinal absorption. Using only stable
      isotopes, intestinal calcium absorption in children with renal failure was found
      to follow a similar pattern to that in adult patients.

PMID- 9569563
TI  - Estimation of extracellular water by means of stable bromine and X-ray
      fluorescence analysis.

PMID- 9569562
TI  - Fat and water photon scattering data for in vivo lean and fatty tissue
      composition studies.
AB  - Photon scattering cross-section data for freshly excised and filtered liquid pig
      fat was measured in the interval chi = 0.02 to 0.64 A-1 (chi =
      E*[sin(theta/2)]/12.4; E being the photon incident energy (keV) and theta the
      scattering angle). The experimental results demonstrate that the marked
      intermolecular effects of coherent scattering in the forward direction can be
      exploited as a tool for characterizing lean and fatty tissue.

PMID- 9569564
TI  - Changes in body composition during adjuvant chemotherapy for breast cancer.

PMID- 9569565
TI  - Body protein as a prognostic instrument for cancer patients?
AB  - Many cancer patients are affected by loss of appetite, weight loss and fatigue in
      the course of disease. These symptoms reduce the patients' quality of life,
      increase morbidity, and lessen tolerance to anti-tumor treatment. In some cases
      the symptoms are partly caused by various treatment modalities. The aim of this
      study was to investigate if radiotherapy affects the body weight and body protein
      of patients, and if changes in body protein have any clinical significance.

PMID- 9569567
TI  - Optimisation of a polarised X-ray source for the in vivo measurement of platinum
      in head and neck tumours.
AB  - There is a continuing need to improve the understanding of kinetics of platinum
      based chemotherapeutic agents, such as cisplatin and paraplatin. Although these
      agents demonstrate highly effective anti-cancer activity, they also have
      associated, often dose-limiting, side-effects such as nephrotoxocity. In vivo X
      ray fluorescence (XRF) has been proven to be a suitable technique for measuring
      the uptake of these agents in tumour and critical organs, but radioisotope based
      systems have not found their way into routine clinical use due to their rapid
      increase in minimum detection limit (MDL) with depth. Polarised X-rays offer a
      solution to this problem by reducing the scattered background, which not only
      reduces the MDL, but also allows the intensity of the source to be increased
      without saturating the detector electronics. This paper describes the development
      and optimisation of a polarised XRF system for in vivo measurement of platinum in
      head and neck tumours, whose response to cisplatin is often unpredictable. The
      polarised X-ray source comprises a clinical X-ray therapy unit (the Pantak DXT
      300) with removable purpose-built collimators. Optimisation studies have
      concentrated upon the operating voltage, polariser material and additional
      filtering. The optimum voltage was found to lie within the range 200-300 kV for
      all polarising materials. There was no significant difference using copper,
      aluminium or iron as the polariser. Increasing the additional filtering improved
      the MDL for a preset number of counts, but decreased the count-rate
      significantly, resulting in unacceptably long counting times. An MDL of 9 ppm was
      achieved for a phantom depth of 2 cm, using a copper polariser, 0.25 mm of tin
      filtering and an operating voltage of 220 kV. TLD measurements showed that the
      corresponding skin dose was 6 mGy. These results indicate a factor of improvement
      in the MDL from the previous 99mTc system, for a factor of two lower skin dose.
      The detection limit achieved is the lowest reported to date, and is considered
      adequate for a comprehensive patient study. It is anticipated that this will
      yield better information and the pharmacokinetics of platinum compounds and will
      lead to optimisation of both chemo and radiotherapy treatment. Additionally this
      technique can be easily integrated into any radiotherapy based department.

PMID- 9569566
TI  - Body composition measurements using DXA and other techniques in tamoxifen-treated
      patients.
AB  - Tamoxifen is an anti-oestrogenic drug which is widely used in the treatment of
      patients with breast cancer. There is increasing interest in using the drug both
      for benign breast disease and as a chemo-preventative agent of the drug in women
      at high risk of breast cancer. Despite the fact that the acute side-effects of
      the drug are few, its agonistic and antagonistic oestrogenic effects are not
      fully known and may have some undesirable effects for patients treated with the
      drug for several years. A number of studies carried out recently indicate a
      varying degree of change in bone mineral content following treatment with
      tamoxifen. These studies concentrated mainly on bone mineral density measurements
      only and non of them reported the effects of tamoxifen on lean body mass and fat
      mass. In this study we measured lean body mass and fat mass in tamoxifen-treated
      females and a comparison group to determine the difference between the two
      groups. Twenty-six women receiving tamoxifen (20 mg/d) have participated in this
      study. The control group comprised 31 healthy women of a similar age. Total body
      bone mineral (TBBM) was measured using a dual-energy X-ray absorptiometry (DXA)
      (Hologic INV., Waltham, U.S.A.). Similarly, regional and total body soft tissue
      (lean and fat tissue) were measured using the DXA system. In addition to DXA
      measurements, percentage body fat (%BF) was measured using total body potassium
      counting (TBK), skinfold anthropometry (SF), infrared interactance (i.r.) and
      bioelectric impedance analysis (BIA). Results from DXA alone showed that there
      were no significant differences between the two groups for TBBM, regional and
      total body lean tissue mass. However, there was a significant difference between
      the two groups (P < 0.05) for %BF measurement. Similarly there was a significant
      difference between the two groups (P < 0.05) for %BF measured by other body
      composition techniques. Although there is no other research reported on the
      effects of tamoxifen on %BF, this retrospective study indicates that tamoxifen
      may lead to increase in fact content in women who are subjected to this
      treatment. We conclude that this observation is probably related to the agonistic
      oestrogenic effect of Tamoxifen on body fat. To our knowledge this deleterious
      effect has not been reported before and it should be taken into considerable when
      comprising different types of anti-oestrogenic drugs. Furthermore, patients
      should be warned about this side-effect when they are prescribed Tamoxifen
      therapy.

PMID- 9569568
TI  - Quantification of lymphoedema using multi-frequency bioimpedance.

PMID- 9569569
TI  - Body composition of HIV/AIDS males: effects of treatment with insulin-like growth
      factor (IGF-I) and growth hormone (GH).

PMID- 9569571
TI  - Fat-free mass, muscle bulk and strength in liver disease.

PMID- 9569570
TI  - The effects of inflammation-mediated osteoporosis (IMO) on the skeletal Ca/P
      ratio and on the structure of rabbit bone and skin collagen.
AB  - The relationships between the skeletal Ca/P ratio (used as an index of bone
      quality) and structural changes in the bone and skin was studied in inflammatory
      mediated osteoporosis (IMO). The bone Ca/P ratio in IMO rabbits was significantly
      lower than in controls. Also, severe alterations were detected at the
      ultrastructural level in bone and skin collagen fibrils from IMO rabbits.

PMID- 9569572
TI  - Risk factors for loss of lean body mass after liver transplantation.
AB  - BACKGROUND: After liver transplantation there is a fall in lean body mass. AIMS:
      To determine the risk factors for this fall in lean body mass using univariate
      and subgroup analyses. PATIENTS AND METHODS: Dual energy X-ray absorptiometry was
      performed in 36 patients (12 with Child-Pugh Class A, 20 with Class B and 4 with
      Class C disease) before and up to 24 months after liver transplantation.
      Univariate and sub-group comparative analyses were performed to assess possible
      risk factors for the fall in lean body mass post-transplantation. RESULTS: The
      pre-transplantation serum albumin inversely correlated with the fall lean body
      mass at 1 month (r = 0.55; p < 0.009) and at 6-9 months (r = 0.51; p < 0.05) post
      transplantation. A positive correlation between the fall in lean body mass and:
      (i) cumulative dose of steroids administered at 2-5 months (r = 0.57; p < 0.05)
      and (ii) length of hospital stay after transplantation (r = 0.52; p < 0.05) were
      also observed. Neither the severity or presence of cholestatic liver disease pre
      transplant, nor acute cellular rejection post-transplant were risk factors for a
      fall in lean mass. DISCUSSION: A hypercatabolic state post-transplant
      (represented by low albumin pre-transplantation), immobility, lack of exercise
      and steroid induced catabolism of muscle may cause the observed fall in lean mass
      after liver transplantation. Earlier transplantation of patients with better
      nutritional status and the use of low dose steroid immunosuppressive regimens may
      prevent the observed fall in lean body mass after transplantation.

PMID- 9569573
TI  - Body composition in renal failure and the effect of dialysis.

PMID- 9569575
TI  - Determination of total body water by IVNAA and 40K counting in young normal and
      growth hormone deficient adults.

PMID- 9569574
TI  - Only a temporary increase of the amount of body protein during long-term
      treatment with growth-hormone (GH) of adults with GH-deficiency (GHD).

PMID- 9569576
TI  - Monte Carlo methods for the in vivo analysis of cisplatin using X-ray
      fluorescence.
AB  - A Monte Carlo method has been used to model the measurement of cisplatin uptake
      with in vivo X-ray fluorescence. A user-code has been written for the EGS4 Monte
      Carlo system that incorporates linear polarisation and multiple element
      fluorescence extensions. The yield of fluorescent photons to the mainly Compton
      scattered background is computed for our detector arrangement. The detector
      consists of a mutually orthogonal arrangement of X-ray tube, aluminium polariser
      and high purity germanium scintillation detector. The influence of tube voltage
      on the minimum detectable concentration is modelled for 100 through 150 kVp X
      radiation. The code is able to predict absorbed dose to the patient which will
      influence the optimal choice of tube voltage. The influence of alterations to
      collimator design and scatterer construction can also be examined. A minimum
      detectable concentration of 50 ppm is determined from measurements with a 115 kVp
      X-ray source and a 615 ppm cisplatin sample in a water phantom.

PMID- 9569577
TI  - A new approach to monitoring trace element concentrations and speciation in
      wounds and wound fluids.
AB  - Combined application of potentiometric stripping analysis (PSA) and computer
      simulation of speciation analysis has been used to determine the total element
      concentrations and the proportions of the different chemical species of copper,
      manganese and zinc present in human would fluids. With samples of 0.5 to 1 cm3
      the coefficient of variation lies in the range of 5-10%. In eight patients the
      concentrations of Cu and Zn were greater than those expected in blood plasma, but
      for Mn the observed concentrations lay with the range expected for plasma.

PMID- 9569578
TI  - Quantitative ultrasound (QUS) on a specific region of interest (ROI) of the Os
      calcis: a new imaging technique.
AB  - Broadband ultrasound attenuation was measured in 28 premenopausal women, 30
      postmenopausal women, and 25 men using a new imaging device, the DTU-one. Short
      term in vivo precision was 1.2 CV%. The r-values for the correlation of BUA vs
      BMD at the hip, spine and lower forearm were 0.66, 0.64 and 0.62, respectively.

PMID- 9569579
TI  - Variation in bone mineral density between different anatomical sites in a normal
      local population.
AB  - Bone mineral density (BMD) measured using dual energy X-ray absorptiometry (DXA)
      can be expressed in terms of standard deviations, above or below mean young adult
      T-scores and above or below age-matched Z-scores. The differences between the
      left neck of the femur (LN), right neck of the femur (RN) and lumbar spine (L2
      L4) were statistically significant, irrespective of whether expressed as T-scores
      or Z-scores. Therefore skeletal status assessment should involve as many sites as
      practically possible. Considering the low radiation dose and short scanning time,
      it is suggested that at least the two femurs and lumbar spine BMD be used in
      routine osteoporosis risk assessment.

PMID- 9569580
TI  - Calcium kinetic investigations and their clinical use.
AB  - Pool sizes and internal fluxes of minerals can be quantitatively determined by
      tracer-kinetic investigations and compartmental analysis. Investigations
      performed in 252 patients revealed characteristic patterns for calcium pools and
      fluxes with respect to disease. The method provides a useful diagnostic tool in
      the early detection of metabolic bone disorders and in problems of differential
      diagnostics.

PMID- 9569581
TI  - In vivo bone mineral studies on volunteers during a 370-day antiorthostatic
      hypokinesia test.
AB  - Bone mineral of spine, femur, tibia, forearm, calcaneus, hand, and foot was
      studied on nine volunteers by quantitative computed tomography, neutron
      activation analysis, single and dual photon absorptiometry during and after long
      term hypokinesia. Conditions of long-term space flight were simulated using a 370
      day antiorthostatic hypokinesia test. It is shown that the highest mineral losses
      occur in foot bones including calcaneus. Remedial measures undertaken delay the
      process of osteoporosis development but do not completely exclude it. The results
      obtained by different methods are often conflicting. Consequently, the accuracy
      of the in vivo methods for bone mineral determination must be more thoroughly
      studied.

PMID- 9569582
TI  - In vivo and in vitro neutron activation analysis for studying the bones of
      children with rickets-like diseases before and during treatment.

PMID- 9569583
TI  - Improvements to the in vivo measurement of cadmium in the kidney by neutron
      activation analysis.
AB  - The McMaster University in vivo cadmium measurement system has been upgraded. Two
      large surface area hyperpure germanium planar detectors (51 mm diameter x 21 mm
      depth) are now employed for the detection of the 559 keV gamma-ray signal from
      cadmium. Phantom studies indicate that the new detectors have significantly
      improved the system. The detection limit in kidney phantoms has been reduced from
      8.9 to 3.8 mg for the same dose and measurement time.

PMID- 9569584
TI  - Longitudinal measurements of the cadmium burden of 'jig solderers' using IVNAA.
AB  - The liver and kidney cadmium burdens of a population of 10 'jig solderers' were
      measured in 1983 and 1995 using similar IVNAA measuring systems. Cadmium exposure
      ceased in 1985. No significant variation in kidney content was observed. The mean
      body burden had fallen by 18%, due to a decrease of mean liver content of 35%.

PMID- 9569585
TI  - Assessment of lead exposure of children from K-XRF measurements of shed teeth.
AB  - Lead is accumulated and immobilized for long periods of time in teeth. Thus the
      Pb concentration of a tooth can be used as an indicator of the cumulative Pb
      intake of a child. Shed and extracted teeth were collected from children in
      Beijing, China and some industrial regions in the Middle Urals in Russia. The Pb
      levels in the teeth were measured in Philadelphia, PA using an X-ray fluorescence
      (XRF) technique. Since Pb deposits in the tooth during the entire period that it
      is in the child, the measured tooth Pb level was divided by the age of the child
      when the tooth was shed and expressed in terms of (microgram/g-yr). 10% (n = 100)
      of the teeth from Beijing, China had Pb levels exceeding 5.5 and 3% above 9
      micrograms/g-yr. For comparison, in the 1970s when urban environmental Pb levels
      were elevated, the tooth Pb levels in Philadelphia children were similar, i.e.
      10% (n = 298) of the teeth had Pb levels exceeding 7.5 and 6% were above 9
      micrograms/g-yr. Children in a more rural setting, Bennington, VT, had no
      detectable tooth Pb (n = 200). The Pb levels in the teeth from the Urals were
      much higher; 50% (n = 134) of the teeth had Pb levels exceeding 7.5 and 10%
      exceeding 17.8 micrograms/g-yr. The tooth Pb levels observed in the teeth from
      Beijing, and more so from the Urals, indicate that these children are residing in
      Pb polluted environments. Further studies are required to determine the extent of
      the Pb pollution and to explore the possibility that there are associated Pb
      related health deficits.

PMID- 9569586
TI  - Computer aided design of a polarised source for in vivo X-ray fluorescence
      analysis.
AB  - A system has been developed which uses Monte Carlo computer simulations to aid
      the design and optimisation of a polarised source for in vivo X-ray fluorescence
      (XRF) analysis of heavy metals: The system is based on a version of the Monte
      Carlo code EGS4 which includes polarised photon interactions, running on a
      personal computer. The code was used to construct a model of a clinical polarised
      XRF system (based on a 300 kV therapy X-ray source) under development at Swansea
      for the measurement of Pt-based chemotherapy drugs in head and neck tumours.
      Several simulations were performed to investigate the variation of XRF
      measurement sensitivity with the material composition and geometry of the system
      components. Pt XRF spectra generated by the model were found to be in good
      agreement with experimental data. The optimum operating voltage for the system,
      predicted by the simulations and confirmed by experiment, was approx. 200 kV. The
      accuracy of the results obtained to date indicates that this technique will
      greatly facilitate future design and optimisation studies of a wide variety of
      XRF systems.

PMID- 9569587
TI  - In vivo XRF as a means to evaluate the risk of kidney effects in lead and cadmium
      exposed smelter workers.
AB  - The effect on kidney function was studied in 22 smelter workers with concomitant
      exposure to lead and cadmium. One active and five retired workers showed early
      signs of kidney dysfunction. They all had a long-term and high lead exposure,
      while their kidney cadmium concentrations measured in vivo by XRF techniques were
      low to moderate. Thus, the exposure to lead has been a greater risk, although an
      interaction between lead and cadmium could not be excluded.

PMID- 9569588
TI  - In vivo X-ray fluorescence (XRF) measurement of uranium in bone.
AB  - This study investigates the applicability of X-ray fluorescence (XRF) to
      measuring bone uranium concentrations, using a 57Co source to excite the uranium
      X-rays, with the source and detector in an approximate 180 degrees backscatter
      geometry relative to the sample position. It is demonstrated, by experiment and
      Monte Carlo simulation, that the X-ray to coherent peak ratio is linearly related
      to concentration and is independent of variations in source-sample geometry,
      thickness of overlying tissue and tibia size. Preliminary in vivo measurements
      indicate a minimum detectable concentration (MDC) of approximately 20
      micrograms/g, which may not be sufficiently sensitive for monitoring occupational
      workers. However, a larger study of occupationally exposed individuals as well as
      work with subjects with known significant accidental uranium exposures is
      necessary to assess the clinical usefulness of this system.

PMID- 9569589
TI  - Development of an accelerator based determination of aluminum burden in
      peripheral bone by neutron activation analysis.

PMID- 9569590
TI  - In vivo X-ray fluorescence for estimation of essential and toxic trace elements
      in teeth.

PMID- 9569591
TI  - Assessment of body fat and lean in the elderly by measuring body carbon and
      oxygen: validation against hydrodensitometry.
AB  - Based on the observation that the carbon-to-oxygen ratio (C/O) in tissue is a
      measure of fat content, we developed a model which correlates C/O to percent body
      fat. Carbon and oxygen mass and their ratio are measured in vivo by fast neutron
      inelastic scattering, using a miniature D-T neutron generator, at a radiation
      exposure of less than 0.06 mSv. We tested the validity of this model against
      hydrodensitometry with 19 healthy adult volunteers. The method was found to be
      accurate and insensitive to assumptions about the composition of lean tissue and,
      therefore, appropriate for studying the elderly and patients with catabolic
      conditions.

PMID- 9569592
TI  - Adult changes in body composition are associated with changes in cholesterol
      levels: the Fels longitudinal study.
AB  - Serial data from 507 adult participants in the Fels Longitudinal Study were used
      to study relationships between average annual changes in serum cholesterol levels
      and annual changes in total body fat, fat-free mass, percent body fat or body
      mass index in men and women aged 18-45 years or 45-65 years. Average annual
      changes in adiposity before and after 45 years of age for men and women show
      statistically significant, strong, positive relationships with corresponding
      changes in cholesterol levels.

PMID- 9569593
TI  - In vivo body composition studies in rats: assessment of total body protein.
AB  - The precision and accuracy of a prompt-gamma neutron activation facility
      developed to assess total body protein in rats is estimated. The coefficient of
      variation of nitrogen measurement, as estimated by repeated measurements on 15
      rats, was 5.5% for an equivalent dose of 60 mSv (Q = 20). Good agreement was
      observed in comparing the results of in vivo neutron activation analysis and
      chemical carcass analysis performed by the Kjeldahl method. The application of
      the technique in comparing the effect of a low-fat and a high-fat diet on body
      protein in rats is demonstrated.

PMID- 9569594
TI  - Muscle distribution: variations with body weight, gender, and age.
AB  - Little is known about skeletal muscle distribution in healthy adults. Data were
      collected on 132 healthy, ambulatory, Caucasian women and men, aged 20-89 yr.
      Appendicular skeletal muscle mass multiple regression models were developed to
      assess the relationships between regional skeletal muscle and height, weight,
      age, ethnicity, and extremity lengths. RESULTS: (1) with an increase in body
      weight there is a greater relative increase in upper muscle distribution; (2)
      women have less upper muscle mass compared to men; (3) with increasing age there
      is a relative reduction in upper muscle distribution. The present results
      indicate that skeletal muscle is not a homogenous component, but has at least
      three independent factors, gender, weight, and age, influencing distribution.

PMID- 9569595
TI  - Fat-free mass components in active vs sedentary females aged 55-75 yr.

PMID- 9569597
TI  - Fat-free mass by bioelectrical impedance vs dual-energy X-ray absorptiometry
      (DXA).
AB  - Body composition (BC) assessment is a useful tool for a careful evaluation of
      nutrition status. Bioelectrical impedance analysis (BIA) is a safe, low-cost and
      reliable method for BC assessment. For epidemiological and clinical research in
      children, paediatric-age specific formula for fat-free mass (FFM) prediction from
      BIA is needed. Thus, in 35 children (age 7.7-13.0 years) with different levels of
      body fatness (relative weight for age 70.6-133.8%), FFM was calculated from dual
      energy X-ray absorptiometry (DXA). A regression equation from BIA and DXA data
      was elaborated. The impedance index (ZI = height2/bioelectrical impedance) was
      the strongest predictor of FFM, explaining 89% of its variance. However, the
      variance increased to 96% when body weight was added with ZI in the regression
      model. No variable, including sex and age, contributed to the prediction of FFM
      in the presence of ZI and body weight. The regression formula [FFM = 2.330 +
      0.588 ZI (cm2/omega) + 0.211 Weight (kg) (r = 0.96, SEE = 1.0 kg)], allows a
      reliable prediction of FFM in children from body impedance values.

PMID- 9569596
TI  - Use of fast neutrons for measuring muscle.
AB  - Elemental Partition Analysis (EPA) is a new approach to body composition. A major
      element of the body is measured and then, by means of other measurements, is
      partitioned to the contributing body compartments. We developed a model for
      measuring total body muscle by applying the EPA method to total body phosphorus
      (TBP). We measure TBP (head excluded) by in vivo fast neutron activation analysis
      using the reaction 31P(n, alpha)28 Al. The main contributors to TBP are the bone
      and skeletal muscle. Adipose tissue and the liver contribute less than 3%. We use
      dual-energy X-ray absorptiometry (DXA) to evaluate the contribution of bone to
      TBP. Corrections are applied for the small contributions of the liver and
      adiopose tissue to TBP to derive muscle phosphorous. The technique requires high
      precision measurements for both TBP (+/- 2%) and DXA (+/- 1%). The total body
      radiation exposure for measuring human subjects is 0.60 mSv. We observed that
      nitrogen can also be measured by fast neutron activation analysis through the
      (n,2n) reaction, simultaneously with TBP.

PMID- 9569598
TI  - Lean R value for DXA two-component soft-tissue model: influence of age and tissue
      or organ type.
AB  - Dual-energy X-ray absorptiometry (DXA) is an important new body composition
      method that is based on tissue attenuation of two main photon energies. When the
      two photon energies pass through tissue, attenuation at the lower energy compared
      with that at the higher energy can expressed as a ratio (R), which is used for
      tissue component identification. We tested whether: (1) the R value of lean
      tissue is related to age, and (2) the R value of lean tissue differs between soft
      tissue locations. Elemental content of various tissues from the literature was
      used. Results show that lean R values for 40 keV and 70 keV are independent of
      age and tissue type.

PMID- 9569600
TI  - Estimation of body fat in caucasian and Polynesian women from anthropometric
      measurements.
AB  - Girth measurements provide a simple method for estimation of total body fat that
      can be used over a wide range of percentage body fat (%BF). Well-established
      equations for determining %BF from girth measurements were applied to 42
      Caucasian and 40 Polynesian women. %BF was determined from total body water
      measurement using oxygen-18 dilution. The relationship between the criterion
      measurement of %BF and that calculated from girth measurements differed
      significantly between the two ethnic groups. Assessment of body fat using girth
      measurements should use ethnicity-specific equations.

PMID- 9569599
TI  - Muscle mass and fat mass in relation to bone mineral density in very old men and
      women: the Framingham Heart Study.
AB  - Aim of the study was investigate the cross-sectional relationship between body
      composition and bone mineral density (BMD) in very old men and women. The study
      sample consisted of 504 women and 285 men, aged 72-93 yr, participating in
      examination 22 (1992-1993) of the Framingham Heart Study. Total body BMD,
      regional BMD, and soft-tissue body composition was measured by dual-energy X-ray
      absorptiometry. Both muscle mass and percentage body fat were positively
      associated with total body BMD in women. After adjustment for age, physical
      activity, smoking status, estrogen use, and thiazide use, BMD increased with
      increasing tertile of muscle mass (p = 0.007) and with increasing tertile of
      percentage body fat (p = 0.0001) in women. In men muscle mass, not percentage
      body fat, was positively associated with BMD. After adjustment for potential
      confounders, BMD remained associated with muscle mass only (p = 0.02). These
      results were similar for leg BMD and arm BMD. The study suggests that the
      influence of muscle and fat mass on bone mineral density is different between
      very old men and women.

PMID- 9569601
TI  - Estimates of fat-free mass (FFM) by densitometry, dual energy X-ray
      absorptiometry (DXA), and bioimpedance spectroscopy (BIS) in caucasian and
      Chinese-American women.
AB  - Estimates of fat-free mass (FFM) from dual energy X-ray absorptiometry and
      bioelectrical impedance spectroscopy (BIS) were compared to results obtained by
      densitometry in a group of Caucasian and Chinese-American women. Each group
      included 38 women between the ages of 18 and 24 years. The Chinese-American women
      were significantly shorter in stature, had lower body weights, and lower values
      for FFM compared to the Caucasian women. DXA estimates of FFM were consistently
      lower than those obtained from densitometry; BIS estimates were similar to
      densitometry results.

PMID- 9569602
TI  - Expression and secretion of beta-galactosidase in Saccharomyces cerevisiae using
      the signal sequences of GgpI, the major yeast glycosylphosphatidylinositol
      containing protein.
AB  - New secretory signals and strategies can be attempted to improve the secretion of
      heterologous proteins of biotechnological interest which encounter difficulties
      being exported in yeast. The GGPI gene of Saccharomyces cerevisiae codes for a
      125 kDa glycoprotein transported through the secretory pathway and anchored to
      the plasma membrane by means of a glycosylphosphatidylinositol. The regions
      coding for the secretory signal or also for the first 46 amino acids were tested
      for efficiency in secretion by fusion to the lacZ gene of Escherichia coli
      resulting in the synthesis of the endoplasmic reticulum-targeted 1-22- and 1-68
      GgpIp/beta-gal hybrids. A cytoplasmic form was also examined. The 1-22 beta gal
      is partially transported to the cell surface and in the medium in an
      unglycosylated form. The 1-68 beta gal is completely retained in the
      intracellular membranes and is N-glycosylated in the GgpIp moiety. The amount of
      hybrid protein produced is similar and independent from its targeted site,
      suggesting that translocation through endoplasmic reticulum is not a limiting
      step, whereas the amount of active enzyme is from 50 to 80% lower for the
      endoplasmic reticulum forms compared with the cytoplasmic form. BiP/Kar2p
      putative precursor is accumulated in cells expressing the endoplasmic reticulum
      targeted forms but not in those producing the cytosolic beta-galactosidase or
      over-expressing an endogenous secretory protein. Thus, glycosylation and abnormal
      folding rather than over-expression are among the factors responsible for the
      decreased activity and exit of beta-galactosidase from the endoplasmic reticulum
      and for induction of BiP. The results obtained indicate that the sole secretory
      signal of GgpIp is suitable to drive secretion of foreign products with complex
      folding and point to the importance of the endoplasmic reticulum quality control
      in the secretion of heterologous proteins in yeast.

PMID- 9569603
TI  - HIV hyperimmune globulin or intravenous immune globulin inhibits response to an
      HIV vaccine.
AB  - The murine model was developed to assess the effects of maternally transferred
      HIV hyperimmune globulin or human intravenous immune globulin on the immunization
      of the offspring at 18-21 days of age with rgp 120SF2-complete Freund's adjuvant.
      Either HIV hyperimmune globulin or intravenous immune globulin was administered
      intraperitoneally to post-partum BALB/c mice and was transferred via milk to the
      offspring. Both HIV hyperimmune globulin and intravenous immune globulin
      inhibited the offspring anti-rgp 120SF2 IgG response to the vaccine. The HIV
      hyperimmune globulin inhibition persisted for 28 days after immunization while
      the intravenous immune globulin inhibition was still present at 63 days after
      immunization. In addition, the intravenous immune globulin had a more generalized
      immunosuppressive effect, inhibiting the IgG response to both rpg 120SF2 and an
      additional protein antigen, hen egg-white lysozyme. Effects of maternal or
      exogenously administered pre-existing antibody, including control antibodies
      (intravenous immune globulin), on the newborn response to HIV and other vaccines
      must be carefully evaluated when vaccine studies proceed in newborns.

PMID- 9569604
TI  - Determination of urinary oxalate with oxalate oxidase and peroxidase immobilized
      on to glass beads.
AB  - We have reported the immobilization of barley oxalate oxidase on to alkylamine
      glass beads through glutaraldehyde coupling (Pundir, C. S., Satyapal and Kuchhal,
      N. K. (1993) Clinical Chemistry 39, 1750-1751). The present report describes the
      immobilization of commercially available horseradish peroxidase on to zirconia
      coated arylamine glass beads through diazotization and a new method for the
      discrete assay of urinary oxalate using both immobilized oxalate oxidase and
      peroxidase. In the method, urinary oxalate is precipitated with CaCl2,
      redissolved in HCl and then assayed using immobilized enzymes. The oxalate in 24
      h urine samples from apparently healthy male adults was measured by this method
      and found to be in the range of 12.2-28.0 mg with a mean of 19.8 mg. The
      percentage recovery of added oxalate (17.5 mg/l) was 96.7 +/- 3.4 (mean +/- SD).
      The mean value of urinary oxalate by our method is comparable with those obtained
      by the Sigma kit method. The cost of oxalate determination in 100 urine samples
      by the present method has been compared with that of the Sigma kit method.

PMID- 9569605
TI  - alpha-Factor pro-peptide N-linked oligosaccharides facilitate secretion of the
      insulin precursor in Saccharomyces cerevisiae.
AB  - To evaluate the possible relationship between N-linked glycosylation of the
      Saccharomyces cerevisiae alpha-factor pro-peptide and transport of the alpha
      factor pro-peptide/insulin precursor fusion protein through the Saccharomyces
      cerevisiae secretory pathway, we analysed secretion of insulin precursor
      facilitated by alpha-factor pro-peptides with one or more of the three N-linked
      glycosylation sites removed. Mutation of the three alpha-factor pro-peptide N
      linked glycosylation sites drastically decreased insulin precursor secretion. The
      three alpha-factor pro-peptide N-linked glycosylation sites differ in their
      ability to facilitate secretion of the insulin precursor. The two alpha-factor
      pro-peptide N-linked glycosylation sites localized closest to the insulin
      precursor contributed significantly to secretion, whereas the most N-terminally
      linked glycosylation site did not appear to facilitate secretion. Only correctly
      folded insulin precursor was found in the culture supernatant, regardless of the
      pro-peptide used for secretion, indicating that alpha-factor pro-peptide N-linked
      oligosaccharide chains are not necessary for correct folding of the insulin
      precursor. Thus, N-linked glycosylation facilitates intracellular transport of
      the alpha-factor propeptide/insulin precursor fusion protein through the
      Saccharomyces cerevisiae secretory pathway and secretion of the insulin
      precursor. N-linked glycosylation per se is not sufficient to facilitate
      secretion of the insulin precursor; the position of the N-linked oligosaccharide
      chain on the alpha-factor pro-peptide is important for facilitating efficient
      secretion.

PMID- 9569606
TI  - Heterologous expression of human granzyme K in Bacillus subtilis and
      characterization of its hydrolytic activity in vitro.
AB  - Human granzyme K, a serine protease found in secretory granules of cytotoxic T
      lymphocytes, was produced in its catalytically active form by recombinant
      technology using Bacillus subtilis as host. The enzyme displays 40-45% identity
      to other members of the human granzyme group, and its closest homologue (75%
      identity) is the rat tryptase RNK-tryp2. The recombinant protein can be recovered
      in its mature form from the bacterial culture supernatant and purified by cation
      exchange chromatography. Initial characterization reveals a protein of
      approximately 28 kDa that is specifically labelled by [3H]di-isopropyl
      fluorophosphate. Measurements of Kcat/K(m) for single-residue thioester
      substrates show approximately a two-fold preference for a Lys versus Arg residue
      at Pl. No activity was observed on ester substrates with various other residues
      at the Pl position. Using oligopeptide substrates, the enzyme displays
      peptidolytic activity C-terminal to both Lys and Arg residues with comparable
      rates of hydrolysis. Likewise, substrate hydrolysis is blocked most efficiently
      by inhibitors that contain Lys or Arg at position Pl. The availability of the
      cloned enzyme will facilitate the analysis of biological roles for this novel
      granzyme, and differentiate its activity from that of other granzymes.

PMID- 9569607
TI  - Rendering one autolysis site in Bacillus subtilis neutral protease resistant to
      cleavage reveals a new fission.
AB  - Autolytic degradation of the thermolysin-like proteinase of Bacillus subtilis
      (TLP-sub) is responsible for the irreversible inactivation of the enzyme at
      elevated temperatures. Previously we have reported five cleavage sites in TLP-sub
      [Van den Burg et al. (1990) Biochem. J. 272, 93-97]. In an attempt to render the
      enzyme less susceptible to autolytic breakdown, one of the fission sites, located
      between Leu-156 and Ile-157, was modified by replacing Ile-157, C-terminally
      located with respect to the fission site, by an Asp residue. Aspartic acid is
      less preferred at this position with respect to the substrate preference of TLP
      sub. Modelling studies indicated that this mutation was unlikely to cause
      conformational changes in the enzyme. Although the 156-157 fission was not
      observed in the mutant enzyme, a new fission site, between Gly-148 and Val-149,
      was now observed.

PMID- 9569608
TI  - Differential induction of macrophage recognition of carrier erythrocytes by
      treatment with band 3 cross-linkers.
AB  - Mouse native and hypotonically loaded erythrocytes were treated with two cross
      linking reagents: bis(sulphosuccinimidyl)suberate (BS3)- and 3,3'-dithiobis
      (sulphosuccinimidyl propionate) (DTSP), excluding clustering agents. Microscopic
      analyses revealed that band 3 cross-linked native and hypotonically loaded
      erythrocytes are more strongly recognized by peritoneal macrophages than native
      and loaded erythrocytes as a result of the cross-linking of band 3 protein in
      accordance with studies in vivo. Macrophage-recognition analyses of 51Cr-labelled
      erythrocytes also demonstrated increased recognition of cross-linked and cross
      linked loaded erythrocytes. This shows that the only action of these two band 3
      cross-linkers on mouse erythrocytes promotes recognition by macrophages without
      requiring the use of clustering agents. The extent of recognition of BS3 cross
      linked and cross-linked loaded erythrocytes by macrophages is dependent on the
      presence or absence of homologous serum or immunoglobulins. In contrast, the
      presence of serum factors or IgG in the incubation medium did not seem to
      influence the recognition of DTSP-modified erythrocytes by macrophages. These
      results seem to indicate a different mechanism of recognition for the
      erythrocytes modified with either one or the other band 3 cross-linker. In
      summary, the unique use of both band 3 cross-linkers procedures can be used to
      target carrier erythrocytes conveying active compounds to macrophages, with
      possible therapeutical applications. Different mechanisms of induction of
      macrophage recognition by these band 3 cross-linkers could reveal differential
      actions on erythrocytes or the involvement of different factors in the
      recognition process.

PMID- 9569609
TI  - Cross-linking treatment of loaded erythrocytes increases delivery of encapsulated
      substance to macrophages.
AB  - Previous investigation has shown that osmotically loaded erythrocytes can act as
      drug carriers in systemic circulation, whereas chemically modified erythrocytes
      can be targeted to organs of the mononuclear phagocytic system because of changes
      introduced in the membrane that are recognized by macrophage cells. In this study
      we have examined the delivery of 125I-labelled carbonic anhydrase (125I-CA)
      carried by mouse erythrocytes, either loaded, or loaded and cross-linked with
      bis(sulphosuccinimidyl)suberate (BS3) and 3,3'-dithiobis-(sulphosuccinimidyl
      propionate), into homologous peritoneal macrophages maintained in culture. The
      hypotonically loaded mouse erythrocytes show a slight recognition by macrophages,
      similar to native erythrocytes. CA loaded into erythrocytes is thus delivered to
      a limited extent into macrophages. Neither the number of recognized loaded 51Cr
      labelled erythrocytes nor the amount of delivered 125I-CA is affected by the
      presence of serum components or IgG. In contrast, cross-linking these loaded
      erythrocytes results in a greater phagocytosis by macrophages as assessed by
      microscopic observations, producing a markedly increased amount of targeted
      enzyme. The amount of CA delivered into macrophages, after BS3 cross-linker
      treatment of erythrocytes, is dependent on the presence of serum components in
      the incubation medium. Thus these cross-linking treatments improve the capacity
      of loaded mouse erythrocytes to deliver significant amounts of targeted enzyme to
      macrophage cells, increasing the therapeutic potential of carrier erythrocytes.

PMID- 9569610
TI  - Production of a hybrid protein consisting of the N-terminal fragment of urokinase
      and the C-terminal domain of urinary trypsin inhibitor in Escherichia coli.
AB  - We have constructed a hybrid protein (ATFHI) consisting of an N-terminal fragment
      from urokinase (ATF) and HI-8, which is the C-terminal domain of urinary trypsin
      inhibitor. The fusion genes for the hybrid proteins were engineered by PCR and
      cloned into expression plasmids. Under the control of the tac promoter, fusion
      genes were efficiently expressed in Escherichia coli. The hybrid proteins,
      produced as inclusion bodies in E. coli, were refolded by a dialysis method and
      purified by ion-exchange chromatography. ATFHI exhibited bifunctional activity
      related to antimetastatic effects: the urokinase receptor-binding activity of ATF
      and the inhibitory activity of HI-8 on plasmin.

PMID- 9569611
TI  - Microbial cell-based biosensor for sensing glucose, sucrose or lactose.
AB  - Biosensors for the determination of glucose, sucrose and lactose were based on a
      Clark-type oxygen electrode covered with a membrane containing microbial cells.
      The glucose-sensing membrane was prepared with intact cells of Gluconobacter
      oxydans immobilized in gelatin cross-linked with glutardialdehyde. The
      disaccharide-sensing membranes were prepared by co-immobilization of G. oxydans
      with cells of Saccharomyces cerevisiae containing invertase for sucrose
      determination and with permeabilized cells of Kluyveromyces marxianus containing
      beta-galactosidase for lactose determination. The strain of G. oxydans that we
      used was able to oxidize both anomers of glucose at the same rate; there was
      therefore no need for mutarotase co-immobilization in disaccharide-sensing
      membranes. The sensitivity of glucose sensor was 50 nA/mM, the range of the
      calibration curve was 0-0.8 mM, the response time was 2 min, and the response
      after 1 week of storage was 62% of the initial response. The parameters of the
      disaccharide sensors were similar: linear range of calibration curve up to 4 mM,
      response time 5 min. The activities of the sensors after 1 week of storage at
      ambient temperature were in the range 50-65% of the initial activity.

PMID- 9569612
TI  - Purification and characterization of a novel levanoctaose-producing levanase from
      Pseudomonas strain K-52.
AB  - Levan-assimilating micro-organisms from soil samples were screened for
      levanoligosaccharide-generating enzyme production. The isolated strain K-52
      produced an extracellular levanoctaose-generating enzyme and was identified as
      belonging to genus Pseudomonas. The levanase was purified to homogeneity by
      (NH4)2SO4 fractionation and successive column chromatography on DEAE-cellulose,
      phenyl-Toyopearl 650 M, Sephadex G-100 and hydroxyapatite. The molecular mass of
      the enzyme was estimated as approx. 38 kDa by both SDS/PAGE and gel filtration,
      and its isoelectric point was approx. pH 4.8. The optimum temperature and pH for
      the enzyme reaction were 35 and 7.0 respectively. The enzyme was stable at a pH
      range of 6.0-9.0 at 4 degrees C and up to 40 degrees C at pH 6.8. The enzyme
      activity was inhibited by Fe2+, Cu2+, Hg2+ and Ag2+. The levanase was specific
      toward 2,6-beta-D-fructosidic linkages of levan and did not hydrolyse other
      polysaccharides such as inulin and dextran. Chemical modification on the levanase
      suggested that cysteine and histidine residues are essential for enzyme activity.
      The levanoctaose liberated by levanase reaction was used selectively only by the
      intestinal beneficial micro-organisms, such as Bifidobacterium and Lactobacillus
      spp.

PMID- 9569613
TI  - Purification and characterization of beta-1,4-glucosidase from Clostridium
      papyrosolvens.
AB  - Clostridium papyrosolvens CFR-1010 was selected for the anaerobic extracellular
      production of beta-1,4-glucosidase. The enzyme was purified by alcohol
      precipitation and DEAE ion-exchange chromatography. Its homogeneity was confirmed
      by SDS/PAGE. The enzyme had a molecular mass of 85 kDa. The maximum enzyme
      activity was observed at pH 5.0 and 50 degrees C. The enzyme activity was
      inhibited by Ca2+, Co2+, Cu2+, Zn2+, Fe2+, Mg2+ and Na+ ions. However, the
      activity increased (158%) in the presence of MnCl2, whereas it decreased by 80%
      in the presence of N-bromosuccinimide, suggesting the presence of tryptophan
      residues at the active site of enzyme. The enzyme had a K(m) of 15 mg/ml and Vmax
      of 125 units/min per mg of protein.

PMID- 9569614
TI  - The physical, chemical and functional properties of lipids in the skin and other
      biological barriers.

PMID- 9569615
TI  - Dissimilar protection of tocopherol isomers against membrane hydrolysis by
      phospholipase A2.
AB  - Porcine pancreatic phospholipase A2 (PLA2) hydrolyses phosphatidylcholine when in
      the lamellar state as well as in the micellar state. We have found that alpha
      tocopherol, the most active form of vitamin E, is able to inhibit PLA2 activity
      only toward lamellar fluid membranes, thus protecting phospholipids toward this
      lytic enzyme. This compound decreases both the initial rate and the extent of
      hydrolysis. The inhibition is of the non-competitive type and the evidence
      strongly suggests that it is due to an effect of alpha-tocopherol on the
      substrate, i.e. the membrane, and not on the enzyme itself. Other tocopherols,
      such as the isomers beta-, gamma- and delta-tocopherol also display PLA2
      inhibition but consecutively to a lower extent. The grade of inhibition of PLA2
      activity by tocopherols correlates well with their biological activity and with
      their location in the bilayer as shown by fluorescence quenching. Cholesterol
      does not inhibit PLA2 activity at concentrations even higher than those of
      tocopherols, indicating that the effect of tocopherols is not due to alteration
      of membrane fluidity. The possible mechanisms underlying the different behaviour
      of tocopherol isomers as PLA2 inhibitors are discussed considering its biological
      significance as membrane stabilizers, suggesting biological actions of compounds
      with vitamin E activity other than their classical roles as antioxidants.

PMID- 9569616
TI  - Synthesis of DL-alpha-tocopherol-ligated phospholipids.
AB  - A three-step synthesis of DL-alpha-tocopheryl-6-O-phosphorylcholine and its -6-O
      phosphorylethanolamine homologue is described. The reaction pathway involves the
      conversion of DL-alpha-tocopherol to the corresponding 2-bromoethyl phosphate,
      hydrolytic cleavage of the remaining phosphorochloridate bond and treatment of
      the diester intermediate formed with either aqueous trimethylamine or ammonia to
      give the aminated target derivatives in good overall yields (61-67%). The
      compounds represent new models of ligated lipid mediators in which a vitamin E
      unit is covalently bonded to a naturally occurring phospholipid fragment.

PMID- 9569617
TI  - Isolation and chemical composition of the ceramide of the Candida lipolytica
      yeast.
AB  - Candida lipolytica yeast was grown batchwise on glucose medium. Ceramide was
      quantitatively isolated from sphingolipid fractions of total lipids by a
      combination of column chromatography and preparative thin-layer chromatography.
      Fatty acids and long-chain bases, obtained after acid methanolysis, were analyzed
      by gas-liquid chromatography. Fatty acid composition was characterized by
      predominance of fatty acids shorter than 20 carbon atoms (72.2% of total fatty
      acids) and by high concentration of fatty acids with 16 carbon atoms (43.3% of
      total fatty acids). The dominant fatty acids were h16:0 and 18:1. The major fatty
      acid with more than 20 carbon atoms was h24:0. Hydroxylated fatty acids
      quantitatively represented almost half of the total fatty acids. The ceramide
      contained an unusual long-chain base composition. Besides the well-known
      trihydroxy bases, 18- and 20-phytosphingosine, which is a common characteristic
      for yeast sphingolipids, a high proportion of more polar bases than the
      trihydroxy ones, was found. The structures of 4,5-dihydroxyicosasphinanine
      (1,3,4,5-tetrahydroxy-2-aminooctadecane) and 4,5-dihydroxyicosasphinganine
      (1,3,4,5-tetrahydroxy-2-aminoeicosane) were tentatively assigned to these bases.
      Their chromatographic properties were identical to those of synthetic bases.

PMID- 9569618
TI  - The presence/absence of Bcl-2, Ca2+/calmodulin-dependent protein kinase IV,
      calretinin and p53 in baker's yeast and wheat germ.
AB  - After removing the nonspecific immunoreactivities from crude extracts of
      Saccharomyces cerevisiae and wheat germ by immunoaffinity chromatography, the
      presence of Ca(2+)-related proteins was tested by Western blot analysis.
      Immunoreactivity for Bcl-2 was absent in the yeast, whereas the immunoreactivity
      was evident in wheat germ and remained unchanged after incubation for 4 h with or
      without actinomycin D. Such incubation caused the degradation of immunoreactive
      peptides of Ca2+/calmodulin-dependent protein kinase IV (CaMPK IV) in the yeast
      and wheat germ. Calretinin and p53 were absent in the yeast and wheat germ. The
      level of cyclic AMP in the yeast increased 100% after incubation for 30 min with
      actinomycin D. These results suggest that actinomycin D may not affect
      intracellular levels of these calcium-related proteins in the yeast and wheat
      germ, and that Bcl-2 occurs in multicellular eukaryotes. Moreover, the cellular
      level of CaMPK IV may vary during the onset of cell division and differentiation.

PMID- 9569619
TI  - Apoptosis in male germinal line cells of rat in vivo: caused by phosphamidon.
AB  - When Wistar strain male albino rats were fed on drinking water containing
      phosphamidon at 35 ppm concentration for 30 days, the spermatogenic compartment
      of the testis underwent histopathological changes. Differentiating spermatids and
      fully differentiated spermatozoa were rare or absent. Uni- and multinucleate
      giant cells appeared in the epithelium as well as the lumen. Semithin sections of
      resin-embedded tissues revealed that such cells had a typical apoptotic
      morphology. These cells were traceable to the caput and cauda epididymidal duct,
      and in the latter they appeared to fragment into apoptotic bodies. The male
      reproductive toxicity of phosphamidon leading to death and removal of the
      spermatogenic line cells through apoptosis is described. It is suggested that
      plastic embedding and semithin sectioning are appropriate methodologies to
      identify apoptotic cells in histological preparations viewed by light microscopy.

PMID- 9569620
TI  - In vitro characteristics of myogenic satellite cells derived from the pectoralis
      major and biceps femoris muscles of the chicken.
AB  - Satellite cells were isolated from the pectoralis major (PM) and biceps femoris
      (BF) muscles of 5-week-old broiler chickens to compare growth and differentiation
      characteristics in vitro. BF cells proliferated at greater rates in the growth
      medium and were more responsive to the mitogenic effects of chicken serum than PM
      cells at all levels tested (p < or = 0.05). When low serum-containing medium was
      administered, the levels of creatine kinase, a marker of differentiation,
      increased at greater rates in PM cultures than in BF cultures (p < or = 0.05).
      Administration of increasing levels of fibroblast growth factor in serum-free
      medium resulted in similar responsiveness of the two lines to this mitogen. No
      differences were detected in rates of protein synthesis or degradation in myotube
      cultures from the two muscle sources. The results suggest that satellite cells
      derived from PM and BF muscles of the chicken have different responsiveness to
      serum mitogens.

PMID- 9569621
TI  - The synaptonemal complexes of the nematode Caenorhabditis elegans: gametic
      response to retinol.
AB  - Retinol (RO) is essential for normal gene expression and progression of
      gametogenesis. Excessive amounts of RO in the diet results in the condition
      termed 'hypervitaminosis A' which severely affects gametogenesis. In the present
      work, the nematode Caenorhabditis elegans was grown in different concentrations
      of RO for up to seven generations. Decreased fecundity was positively correlated
      with increasing concentrations of RO with successive generations. Decreased
      nuclear volume was positively correlated with increasing RO concentration for
      each generation. Abnormal chromatin condensation was present along the bivalent
      and the lengths of the synaptonemal complexes (SC) were consistently longer than
      in the wild-type. Increasing RO concentration was also negatively correlated with
      the presence of SCs. The presence of disjunction regulator regions (DRR), which
      are decondensed regions of chromatin along the bivalent which occur in specific
      numbers, was negatively correlated with increasing RO concentration. By the third
      generation, DRRs were no longer observed in any of the organisms. This study
      shows that high levels of retinol in the diet affect gene expression, via changes
      in chromosome structure, and interferes with gamete production by inhibiting the
      pairing of homologous chromosomes during meiotic prophase.

PMID- 9569622
TI  - Biological effects of macrotetrolide antibiotics and nonactic acids.
AB  - Published results as well as patent applications on biological effects of
      macrotetrolides and nonactic acids are reviewed. Their antimicrobial,
      antiprotozoan (coccidiostatic), antiparasitic (anthelminthic), insecticidal and
      acaricidal (miticidal) effects and also newly described immunosuppressive and
      plant growth stimulating activities are described. Both theoretical papers and
      practical applications including the effects of macrotetrolides on the
      environment are included; a particular target organism and precise dosage (e.g.
      LD50) are reported, in agreement with the original papers. It appears that
      macrotetrolides and their homologs are very prospective bioactive compounds that
      find application in agriculture, forestry, human and veterinary medicine while
      their negative effects on the environment are restricted to a minimum (biological
      quality of soil and water etc.).

PMID- 9569624
TI  - Influence of alkali-treated cornsteep liquor containing medium on protein A
      production by Staphylococcus aureus.
AB  - Staphylococcus aureus cultivated in liquid media containing untreated cornsteep
      liquor (CSL) and alkali-treated CSL produced similar biomass yields (6.5-6.9
      g/L). However, contents of protein A in the biomass was 0.5% and 1.56% for
      untreated CSL and treated CSL, respectively. Addition of treated CSL at 20 g/L
      achieved optimal enhancement of protein A production (0.11 g/L). Probable factors
      associated in treated CSL for the enhanced protein A production are discussed.

PMID- 9569625
TI  - Lack of surface receptors not restriction-modification system determines F4 phage
      resistance in Streptococcus bovis II/1.
AB  - The resistance of Streptococcus bovis strain II/1, the producer of SbvI
      restriction endonuclease, to F4 phage infection was demonstrated by the double
      agar-layer method. Despite the presence of restriction endonuclease SbvI which
      can cleave F4 phage DNA to numerous fragments in vitro, the evidence that
      adsorption inhibition is the most important defence mechanism in phage resistance
      of S. bovis II/1 strain was obtained by adhesion experiments in vivo. Electron
      microscopy of phage-host mixtures showed many phage particles on the bacterial
      surface of phage-sensitive S. bovis 47/3 control strain in comparison with no
      phage particles seen on S. bovis II/1 (phage-resistant) strain surface.

PMID- 9569626
TI  - Antifungal effects of new heterocyclic compounds, 6H-pyrimido[2,1-a]isoindole
      derivatives.
AB  - Minimal inhibitory concentrations for 10 new condensed isoindole derivatives were
      established by the agar diffusion method. Benzo[b]-6H-pyrimido[2,1-a]isoindole-4
      one exhibited a broad antifungal effect; the observed MIC (mg/L) were 7 (K.
      lactis), 8 (C. pseudotropicalis), 17 (W. fluorescens), 22 (E. magnusii), 31 (P.
      membranaefaciens), 32 (S. alluvius) and 32 (S. cerevisiae). The compound also
      inhibited the growth of B. subtilis (MIC 9 mg/L). No effect on the growth of E.
      coli was found.

PMID- 9569631
TI  - In vitro susceptibility of 90 penicillin-susceptible and -resistant pneumococci
      to penicillin G, amoxicillin, amoxicillin/clavulanate, cefaclor, cefuroxime,
      cefpodoxime, cefixime and imipenem.
AB  - In vitro susceptibility of eight antibiotics was compared using three groups of
      pneumococci and agar dilution method comprising 30 penicillin-susceptible, 30
      intermediately penicillin-resistant, and 30 highly penicillin-resistant
      pneumococci. Decreased sensitivity to all beta-lactam agents of intermediately
      penicillin-resistant and highly penicillin-resistant pneumococci is shown. MIC50
      and MIC90 was lower with amoxicillin with and without clavulanate by one dilution
      than with penicillin. Cephalosporin MIC90s were all significantly higher for
      intermediately resistant and fully resistant strains. Only imipenem was more
      active than penicillin with MIC90 of susceptible pneumococci 0.015 mg/L,
      intermediately resistant pneumococci 0.25 mg/L, resistant pneumococci 1 mg/L.

PMID- 9569630
TI  - Effects of temperature and novobiocin on the expression of calf prochymosin gene
      and on plasmid copy number in recombinant Escherichia coli.
AB  - Escherichia coli strain HB101 harboring an expression plasmid bearing calf
      prochymosin gene under the control of the tac promoter was grown in the presence
      of IPTG with or without novobiocin at 28 and 40 degrees C, respectively. The
      differential rates of synthesis of prochymosin inclusions, and, for comparison,
      of beta-lactamase and beta-galactosidase, as well as plasmid copy number, were
      determined during the first hours of steady state growth. At 28 degrees C the
      induced expression of prochymosin gene was almost blocked. Addition of novobiocin
      did not alleviate this effect. In fact, it strengthened it, and we conclude that
      both these additive inhibitory effects are a consequence of the decrease in
      negative superhelical tension of plasmid DNA to an insufficient level. At 40
      degrees C the differential rate of prochymosin synthesis was markedly enhanced.
      Since the copy number of the expression plasmid increased approximately to the
      same extent, we conclude that an increase in gene dose is the cause. The
      stimulation of cloned heterologous gene expression at 40 degrees C and inhibition
      at 28 degrees C may be conveniently used in biotechnological-scale cultivations
      of some recombinant bacteria.

PMID- 9569632
TI  - Antibacterial effects of some 1-substituted 1,2,4-triazoles.
AB  - Seventeen synthetic 1-substituted 1,2,4-triazoles exerted a significant effect on
      the bacteria B. subtilis, S. aureus, E. coli and P. aeruginosa. The least
      sensitive to the effects of the triazoles was S. aureus. With all triazole
      derivatives and their combinations, B. subtilis and P. aeruginosa exhibited IC50
      and MIC values several times higher than with ampicillin. The most effective
      triazoles have a N-phenyl ring or benzimidinoyl ring substituted with one or
      several chlorine atoms. The highest tested concentration of the three most
      effective triazoles influenced the specific growth rate.

PMID- 9569633
TI  - Degradation of polychlorinated biphenyl mixtures by the lignin-degrading fungus
      Phanerochaete chrysosporium.
AB  - Degradation of lower-chlorinated and higher-chlorinated PCB congeners (Delor 103
      and Delor 105 as equivalents of Aroclor 1242 and Aroclor 1254, respectively) by
      the white-rot fungus Phanerochoete chrysosporium was investigated in N-limited
      and non-limited media. No degradation of either Delor 103 or Delor 105 was found
      in a N-limited medium 9 d after their addition whereas in the non-limited medium
      during the same period their levels dropped by 55 and 58%, respectively. The
      degradation was non-specific and no significant differences in the degradation of
      di-, tri-, tetra-, penta-, hexa-, and hepta-congeners were found. No activity of
      Mn-dependent peroxidase (MnP) or lignin peroxidase (LiP) was detectable in the
      non-limited medium. We assume that the degradation of PCBs by P. chrysosporium is
      relatively non-specific, takes place under non-limited conditions and is
      independent of the activities of MnP or LiP.

PMID- 9569634
TI  - Postantibiotic effects of imipenem and enoxacin against S. typhimurium and S.
      enteritidis and the influence on their surface hydrophobicity.
AB  - The influence of the postantibiotic effect (PAE) and the postantibiotic sub-MICs
      effect (PA SME) of imipenem and enoxacin on the surface hydrophobicity of S.
      typhimurium and S. enteritidis strains were studied by evaluating Congo red
      binding and the aggregation in molar solutions of ammonium sulfate (SAT). A PAE
      was induced by 2x and 4 x MIC of antibiotics tested for 0.5 h. Suprainhibitory
      concentrations of imipenem against S. typhimurium induced a short PAE (0.3-0.6 h)
      compared to S. enteritidis (6.0-9.7 h). Suprasubinhibitory concentrations of
      imipenem did not allow a regrowth of S. enteritidis. Similar results were also
      found for enoxacin. Evaluation of surface hydrophobic properties of the
      salmonellas after affecting both PAEs and PA SMEs has shown that imipenem at
      concentrations 4 x MIC and 4 x MIC + 0.3 x MIC partially influenced the
      hydrophobicity of S. typhimurium. S. enteritidis was more susceptible toward both
      antibiotics tested.

PMID- 9569635
TI  - Biochemical characteristics and fermentation of glucose and starch by rabbit
      caecal strains of Bifidobacterium globosum.
AB  - Two strains of Bifidobacterium globosum were isolated from caecal contents of
      rabbits in a search for potential probiotics. Both strains fermented glucose,
      galactose, pentoses, maltose, raffinose and starch. Common coccidiostats
      (monensin, salinomycin) and antimicrobial growth promotors (avoparcin,
      bacitracin, nitrovin, virginiamycin) supplied at 10 mg/L inhibited their growth
      in cultures with glucose. Fermentation parameters of bifidobacteria on glucose
      and starch differed. More formate and ethanol and less lactate were produced
      during growth on glucose than during growth on starch. When growing on starch,
      the two strains of bifidobacteria produced 1 mol lactate per 5.6 and 5.7 mol
      acetate, respectively. Corresponding values during growth on glucose were 17.3
      and 8.4 mol of acetate per mol of lactate. Starch-grown cells accumulated more
      saccharides than cells grown on glucose (1.48 vs. 0.41 and 3.12 vs. 1.18 mmol
      glucose units per 1 g of dry matter, respectively).

PMID- 9569639
TI  - A new specific gene for wasp cellular immune resistance in Drosophila.
AB  - Larvae of Drosophila melanogaster produce a haemocytic reaction against eggs of
      the parasitoid, Asobara tabida, which leads to the formation of a multicellular
      capsule surrounding the foreign object. The same phenomenon was observed with the
      parasitoid, Leptopilina boulardi. Concerning the resistance of D. melanogaster to
      L. boulardi, a single major segregating locus with the resistant allele dominant
      to the susceptible one was found. The host strain susceptible to this parasitoid
      species was found to be highly immune reactive against the eggs of A. tabida. The
      inheritance of the capacity to encapsulate A. tabida was analysed by comparing
      reciprocal crosses made using inbred resistant and susceptible parental strains.
      We conclude that differences in the encapsulation capacity are inherited
      autosomally, with the reactive phenotype showing complete dominance over the non
      reactive one. These data suggest the existence of two independent gene systems,
      each being concerned with the recognition of one species only.

PMID- 9569640
TI  - Further investigation on the regression method of mapping quantitative trait
      loci.
AB  - The simple regression method of mapping quantitative trait loci (QTL) is further
      investigated in comparison with the mixture model maximum likelihood method under
      high heritabilities, dominant and missing markers. No significant difference
      between the two methods is detected in terms of errors of parameter estimation
      and statistical powers, with the exception that the estimation of residual
      variance provided by the regression method is confounded with part of the QTL
      variance. The test statistic profiles show some difference between the two
      methods, but the difference is only detectable at the micro level. An alternative
      method, referred to as iteratively reweighted least squares, is proposed, which
      can correct the deficiency of parameter confounding in the regression method yet
      retains the properties of simplicity and rapidity of the ordinary regression
      method. Like the existing regression method, the weighted least squares method
      can be useful in QTL mapping in conjunction with the permutation tests and
      construction of confidence intervals by bootstrapping.

PMID- 9569641
TI  - Transient expression of the Drosophila melanogaster cinnabar gene rescues eye
      color in the white eye (WE) strain of Aedes aegypti.
AB  - The lack of eye pigment in the Aedes aegypti WE (white eye) colony was confirmed
      to be due to a mutation in the kynurenine hydroxylase gene, which catalyzes one
      of the steps in the metabolic synthesis of ommochrome eye pigments. Partial
      restoration of eye color (orange to red phenotype) in pupae and adults occurred
      in both sexes when first or second instar larvae were reared in water containing
      3-hydroxykynurenine, the metabolic product of the enzyme kynurenine hydroxylase.
      No eye color restoration was observed when larvae were reared in water containing
      kynurenine sulfate, the precursor of 3-hydroxykynurenine in the ommochrome
      synthesis pathway. In addition, a plasmid clone containing the wild type
      Drosophila melanogaster gene encoding kynurenine hydroxylase, cinnabar (cn), was
      also able to complement the kynurenine hydroxylase mutation when it was injected
      into embryos of the A. aegypti WE strain. The ability to complement this A.
      aegypti mutant with the transiently expressed D. melanogaster cinnabar gene
      supports the value of this gene as a transformation reporter for use with A.
      aegypti WE and possibly other Diptera with null mutations in the kynurenine
      hydroxylase gene.

PMID- 9569642
TI  - Functional expression of house fly (Musca domestica) cytochrome P450 CYP6D1 in
      yeast (Saccharomyces cerevisiae).
AB  - Cytochrome P450 CYP6D1 from the house fly is important in the detoxication of
      xenobiotics and in resistance to pyrethroid insecticides. In house fly microsomes
      CYP6D1 requires cytochrome b5 for the metabolism of some substrates, such as
      benzo[a]pyrene, but does not require cytochrome b5 for the metabolism of other
      substrates such as methoxyresorufin. To examine the molecular mechanisms involved
      in its metabolism of pyrethroids and other substrates, a system for the
      heterologous expression of CYP6D1 in the yeast Saccharomyces cerevisiae was
      developed. Heterologous CYP6D1 can be inducibly expressed by culture in media
      with galactose as the sole carbon source, and is successfully inserted into the
      yeast microsomes. CYP6D1 is enzymatically active, as measured by methoxyresorufin
      O-demethylation, indicating that CYP6D1 is able to interact with yeast P450
      reductase. However, CYP6D1 expression did not result in measurable benzo[a]pyrene
      hydroxylation, suggesting that CYP6D1 cannot interact with yeast cytochrome b5,
      or that there is insufficient cytochrome b5 in the yeast microsomes to support
      this CYP6D1-mediated activity. Some suggestions are made for improving the yeast
      microsomal oxidoreductase environment in order to optimize CYP6D1 function.

PMID- 9569643
TI  - cDNAs for a chymotrypsinogen-like protein from two strains of Plodia
      interpunctella.
AB  - Gut proteinases are involved in the solubilization and activation of insecticidal
      toxins produced by Bacillus thuringiensis and may also be involved in resistance
      development. Approximately threefold lower chymotrypsin-like enzyme activity was
      observed in a Bt(entomocidus)-resistant strain of the Indianmeal moth, Plodia
      interpunctella, than that in the Bt-susceptible strain. Because chymotrypsin-like
      proteinases are involved in Bt protoxin activation in P. interpunctella, we
      compared cDNA sequences, mRNA expression levels, and genomic DNA for chymotrypsin
      like enzymes in Bt-susceptible and Bt-resistant strains of P. interpunctella. To
      isolate cDNA coding for chymotrypsinogen-like proteinases, a probe was developed
      using polymerase chain reaction (PCR) amplification of a cDNA library from the Bt
      susceptible strain using a vector primer and a degenerate primer corresponding to
      a conserved sequence in the active site of serine proteinases. This probe was
      used to screen cDNA libraries from resistant and susceptible strains. Predicted
      amino acid sequences from cDNA clones of each strain share similarity with
      sequences of chymotrypsin-like proteinases and are most similar to a chymotrypsin
      like proteinase from the tobacco hornworm, Manduca sexta. cDNAs for putative
      chymotrypsinogen-like proteins, from both Bt-susceptible and Bt-resistant strains
      of P. interpunctella share an identical open reading frame of 846 nucleotides.
      The encoded proteins contain amino acid sequence motifs of serine proteinase
      active sites, disulfide-bridge cysteine residues, and both zymogen activation and
      signal peptides. A difference between these cDNAs was observed only in the
      untranslated region where a substitution of guanine for adenine occurred in the
      Bt-resistant strain. Southern and Northern blotting analyses indicated that there
      are no major differences in chymotrypsinogen-like genomic organization and mRNA
      expression in the two strains. These data suggest that chymotrypsinogen-like
      proteinase genes and their transcription are similar in the Bt-susceptible and Bt
      resistant strains of P. interpunctella.

PMID- 9569644
TI  - The genes encoding the antibacterial sex-specific peptides ceratotoxins are
      clustered in the genome of the medfly Ceratitis capitata.
AB  - Ceratotoxins are antibacterial peptides produced in the female reproductive
      accessory glands of the medfly Ceratitis capitata. Their expression is not
      affected by bacterial infection, but is enhanced after mating and is modulated by
      juvenile hormone. Three different peptides, named ceratotoxins A, B and C, have
      been previously purified from the female accessory gland secretion and their
      amino acid and cDNA sequences have been determined. We report here the complete
      nucleotide sequences of four genes encoding closely related ceratotoxin peptides.
      One of them encodes a novel peptide, which we named ceratotoxin D. Restriction
      and nucleotide sequence analysis indicate that these ceratotoxin genes are
      organized in a large cluster spanning more than 26 kilobases of DNA. All
      ceratotoxin genes are coordinately expressed. Ceratotoxin transcripts appear in 2
      3 day old adult females, and they reach a maximum in 6-7 day old females. The
      presence of highly conserved motifs in the upstream regions of all the sequenced
      ceratotoxin genes suggests the presence of common regulatory elements for all
      ceratotoxins.

PMID- 9569645
TI  - Cloning of cDNA for vitellogenin of the parasitoid wasp, Pimpla nipponica
      (Hymenoptera: Apocrita: Ichneumonidae): vitellogenin primary structure and
      evolutionary considerations.
AB  - The cDNA for vitellogenin (Vg) of the parasitoid wasp Pimpla nipponica
      (Hymenoptera: Apocrita) was cloned and sequenced. The deduced amino acid sequence
      with 1807 residues was obtained. The N-terminal 20 amino acids chemically
      determined for vitellin (Vn) agreed completely with the deduced 20 amino acids
      that follow the 16 amino acid residues for putative signal peptide. The cDNA
      clone for the Vg of the turnip sawfly Athalia rosae (Hymenoptera: Symphyta),
      previously obtained and partially sequenced, was also completely sequenced and
      the amino acid sequence deduced. Amino acid sequences were compared between these
      two species and also with known Vg sequences from other insects. Common to all
      these insects is the presence of two long regions with relatively well-conserved
      amino acid sequences, one near the N-terminal extending 267-282 residues
      (including two cysteines at conserved locations), and the other starting at
      position 450 to 655 and extending 279-283 residues, and of a region at the C
      terminal extending some 200 residues (about 250 in Aedes aegypti due to the
      presence of a serine-rich stretch) with 10 cysteines at conserved locations. A
      molecular phylogenetic tree was constructed.

PMID- 9569646
TI  - Differential display of mRNAs related to amino acid metabolism in the
      endosymbiotic system of aphids.
AB  - Bacteriocytes harbouring Buchnera endosymbionts were isolated from young and old
      aphids, Acyrthosiphon pisum, and their mRNA populations were examined by the
      differential cDNA display and quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) technique. It was suggested that several gene products are
      produced when the symbiotic system is well organized in the young insect, whereas
      others are produced after the system becomes degenerate in old aphids. Among the
      gene products that were actively synthesized in the symbiotic system of the young
      host were putative aspartate aminotransferase, homoserine kinase and N
      acetylglutamate synthase. These findings were consistent with the hypothesis that
      the symbiotic system utilizes glutamate to produce essential amino acids.

PMID- 9569647
TI  - Rapid induction by a blood meal of a carboxypeptidase gene in the gut of the
      mosquito Anopheles gambiae.
AB  - A search for genes induced rapidly (< 3 h) after a blood meal in the gut of the
      human malaria vector Anopheles gambiae led to the identification of a
      carboxypeptidase gene (AgCP). We report the sequence of the 1302 nt AgCP
      transcribed sequence, 710 nt of upstream and 585 nt of downstream DNA. The AgCP
      open reading frame is 60.4% identical at the nucleotide level to a blackfly,
      Simulium vittatum, carboxypeptidase gene. The transcriptional start site of AgCP
      was determined by primer extension. Expression of AgCP mRNA is detectable in the
      guts of pupae and sugar-fed adult female mosquitoes and is induced (approximately
      10-fold) within 3 h of a blood meal. By 24 h after a blood meal, mRNA abundance
      returns to a level close to that present before a blood meal. Whole-mount in situ
      hybridization shows that AgCP mRNA expression is restricted to most or all cells
      of the posterior midgut. Expression of the AgCP and trypsin genes were compared
      and shown to differ in two fundamental ways: (1) the peak of AgCP expression
      after a blood meal occurs approximately 20 h before that of trypsin; and (2)
      induction of the AgCP gene is independent of the composition of the ingested meal
      whereas trypsin induction requires the presence of protein. The potential use of
      the AgCP promoter for driving the expression of genes that hinder the development
      of parasites in the mosquito gut is discussed.

PMID- 9569648
TI  - Spontaneous trait transference: communicators taken on the qualities they
      describe in others.
AB  - Spontaneous trait transference occurs when communicators are perceived as
      possessing the very traits they describe in others. Study 1 confirmed that
      communicators become associated with the trait implications of their descriptions
      of others and that such associations persist over time. Study 2 demonstrated that
      these associations influence specific trait impressions of communicators. Study 3
      suggested that spontaneous trait transference reflects simple associative
      processes that occur even when there are no logical bases for making inferences.
      Finally, Study 4 used more naturalistic stimuli and provided additional evidence
      that the phenomenon reflects mindless associations rather than logical
      attributions. Together these studies demonstrate that spontaneous trait
      transference is a reliable phenomenon that plays a previously unrecognized role
      in social perception and interaction.

PMID- 9569649
TI  - The relation between perception and behavior, or how to win a game of trivial
      pursuit.
AB  - The authors tested and confirmed the hypothesis that priming a stereotype or
      trait leads to complex overt behavior in line with this activated stereotype or
      trait. Specifically, 4 experiments established that priming the stereotype of
      professors or the trait intelligent enhanced participants' performance on a scale
      measuring general knowledge. Also, priming the stereotype of soccer hooligans or
      the trait stupid reduced participants' performance on a general knowledge scale.
      Results of the experiments revealed (a) that prolonged priming leads to more
      pronounced behavioral effects and (b) that there is no sign of decay of the
      effects for at least 15 min. The authors explain their results by claiming that
      perception had a direct and pervasive impact on overt behavior (cf. J.A. Bargh,
      M. Chen, & L. Burrows, 1996). Implications for human social behavior are
      discussed.

PMID- 9569650
TI  - The impact of accuracy motivation on interpretation, comparison, and correction
      processes: accuracy x knowledge accessibility effects.
AB  - Four studies provide evidence for the notion that there may be boundaries to the
      extent to which accuracy motivation may help perceivers to escape the influence
      of fortuitously activated information. Specifically, although accuracy
      motivations may eliminate assimilative accessibility effects, they are less
      likely to eliminate contrastive accessibility effects. It was found that the
      occurrence of different types of contrast effects (comparison and correction) was
      not significantly affected by participants' accuracy motivations. Furthermore, it
      was found that the mechanisms instigated by accuracy motivations differ from
      those ignited by correction instructions: Accuracy motivations attenuate
      assimilation effects because perceivers add target interpretations to the one
      suggested by primed information. Conversely, it was found that correction
      instructions yield contrast and prompt respondents to remove the priming event's
      influence from their reaction to the target.

PMID- 9569651
TI  - Concealable stigmas and positive self-perceptions: feeling better around similar
      others.
AB  - In an 11-day experience-sampling study, 86 Harvard undergraduates rated their
      momentary self-esteem and affect and then described the who, what, and where of
      their daily lives. Those with concealable stigmas (students who indicated that
      they were gay, that they were bulimic, or that their family earned less than
      $20,000 each year) reported lower self-esteem and more negative affect than both
      those whose stigmas were visible and those without stigmatizing characteristics.
      Only the presence of similar others lifted the self-esteem and mood of students
      with concealable stigmas, and these particular students were the least likely to
      experience such occasions. Thus, contact with similar others protects the
      psychological self from negative cultural messages.

PMID- 9569652
TI  - Pleasure and pain in doing well, together: an investigation of performance
      related affect in close relationships.
AB  - In a series of four studies, the self-evaluation maintenance (SEM) model is used
      to predict peoples' self-reported affective responses to doing better or worse
      than their partners. Both self-protective reactions to comparison (i.e., those
      predicted by the original SEM model) and empathic reactions to the partner's
      response (i.e., those predicted by the extended SEM model) were obtained. In
      addition, as predicted on the basis of both models, comparisons with romantic
      partners resulted in a different pattern of self-reported affect than did
      comparisons with strangers. Unexpectedly, it appeared that empathic effects were
      minimal or absent among dating partners when comparisons were in areas of high
      self-relevance.

PMID- 9569653
TI  - Is self-enhancement healthy? Conceptual, psychometric, and empirical analysis.
AB  - Whereas S.E. Taylor and J.D. Brown (1988) proposed that positive illusions foster
      mental health, C.R. Colvin, J. Block, and D.C. Funder (1995) presented empirical
      evidence that suggested the opposite: The extent to which self-ratings are more
      favorable than ratings by others (self-enhancement) is correlated with
      unfavorable personality traits (self-enhancement correlation). Our conceptual
      analysis shows that these propositions are not incompatible. Our psychometric
      analysis reveals that self-enhancement correlations are a function of the self
      other agreement and the consensus of others across 830 traits indicates that (a)
      self-enhancement is consistent across highly evaluative traits, but not across
      traits low in evaluativeness, and (b) self-enhancement correlations are minimal
      for non-evaluative traits and increase with increasing trait evaluativeness. We
      conclude that people consistently differ in their tendency to enhance their trait
      descriptions and that this tendency is linked to the unfavorability of their
      traits.

PMID- 9569654
TI  - Individual differences in adult ego development: sources of influence in twins
      reared apart.
AB  - A behavior genetic analysis of the personality dimension of ego development, as
      assessed by the Washington University Sentence Completion Test, was carried out
      on a sample of 45 pairs of monozygotic twins and 28 pairs of same-sex dizygotic
      twins. The twins ranged in age from 16 to 70 years at the time of assessment, had
      been separated during infancy, and had been raised apart in adoptive homes before
      being reunited in adulthood. Analyses indicated that reared-apart twins were
      similar in trait levels of ego development and that such similarity could not
      solely be attributed to measured similarity in cognitive ability, including
      verbal reasoning. Estimates of broad similarity for ego development (46%) were
      comparable to values reported for other major personality dimensions. Phenotypic
      variance in adult levels of ego development appears to have substantial genetic
      and environmental sources.

PMID- 9569655
TI  - Gender-related individual differences and the structure of vocational interests:
      the importance of the people-things dimension.
AB  - In 3 studies (respective Ns = 289, 394, and 1,678), males and females were
      assessed on Big Five traits, masculine instrumentality (M), feminine
      expressiveness (F), gender diagnosticity (GD), and RIASEC (Realistic,
      Investigative, Artistic, Social, Enterprising, Conventional) vocational interest
      scales. Factor analyses of RIASEC scores consistently showed evidence for D.J.
      Prediger's (1982) People-Things and Ideas-Data dimensions, and participants'
      factor scores on these dimensions were computed. In all studies Big Five Openness
      was related to Ideas-Data but not to People-Things. Gender was strongly related
      to People-Things but not to Ideas-Data. Within each sex, GD correlated strongly
      with People-Things but not with Ideas-Data. M, F, and Big Five measures other
      than Openness tended not to correlate strongly with RIASEC scales or dimensions.
      The results suggest that gender and gender-related individual differences within
      the sexes are strongly linked to the People-Things dimension of vocational
      interests.

PMID- 9569656
TI  - Learned helplessness and the occurrence of depressive-like and paranoid-like
      responses: the role of attentional focus.
AB  - Five experiments were performed to examine different manifestations of depressive
      and paranoid-like responses after failure in unsolvable problems. Participants
      were exposed to no feedback, "universal" failures, or "personal" failures while
      their attention was focused on either themselves or the experimenter. Then,
      depressive and paranoid-related states of mind, interfering thoughts, self
      schemata, others-schemata, and autobiographical memories were measured. Findings
      indicated that when attention was focused on the self, personal failure was
      effective in producing depressive-like reactions. When attention was focused on
      the threatening agent (experimenter), participants reacted to the exposure to
      personal failure with paranoid-like responses. Universal failure failed to
      produce either depressive- or paranoid-like reactions. The discussion focuses on
      the association between personal learned helplessness and psychopathology and on
      the role of attentional focus.

PMID- 9569658
TI  - Interpreting personality profiles across cultures: bilingual, acculturation, and
      peer rating studies of Chinese undergraduates.
AB  - Prior research (R.R. McCrae, P.T. Costa, & M.S. Yik, 1996) using a Chinese
      translation of the Revised NEO Personality Inventory suggested substantial
      differences between Hong Kong and North American undergraduates. Study 1, with a
      sample of bilingual Hong Kong students (N = 162), showed that prior findings were
      not due simply to the translation. Study 2, with undergraduates of European and
      Chinese ancestry living in Canada (N = 633), suggested that more of the
      differences were cultural in origin. Study 3, which used peer ratings of Chinese
      students (N = 99), replicated most Study 2 results, suggesting that exposure to
      Canadian culture increased openness, cheerfulness, and prosocial behavior and
      attitudes. Differences in sense of competence and vulnerability to stress
      appeared to be due to different cultural standards for judging these traits.
      Together, the 3 studies illustrate an integrated approach to interpreting
      personality differences across cultures.

PMID- 9569657
TI  - Individual differences in the acquisition of affectively valenced associations.
AB  - Two studies were conducted to test the predictions derived from the behavioral
      activation system and behavioral inhibition system theory of personality that
      trait anxiety is positively related to the speed of acquisition of punishment
      expectancies and impulsivity is positively related to the speed of acquisition of
      reward expectancies. Both studies used a standard approach-avoidance
      discrimination task with self-report measures of expectancies. Both studies found
      support for the hypothesized relation between trait and acquisition of punishment
      expectancies but not for the hypothesized relation between impulsivity and
      acquisition of reward expectancies. Study 2 suggested that the relation between
      trait anxiety and punishment expectancy is affected by the type of incentive and
      the type of trait anxiety measure used. The results suggest that highly trait
      anxious individuals are more susceptible to developing new sources of anxiety
      than others.

PMID- 9569659
TI  - Depressive realism from the perspective of cognitive-experiential self-theory.
AB  - To explain why the depressive realism effect has been found in trivial,
      artificial laboratory but not in more realistic or emotionally engaging
      situations, the authors hypothesized that depressed people overcompensate for a
      tendency toward maladaptive experiential (intuitive) processing by exercising
      excessive rational control in trivial situations. In more consequential
      situations, they are unable to control their maladaptive experiential processing
      because it is excessive, or their rational control is insufficient, or both. As
      predicted, a subclinically depressed group (n = 39) made more optimal decisions
      than a nondepressed control group (n = 36) under trivial conditions, and the
      groups converged under more consequential conditions, with the depressed group
      responding less and the control group more optimally. Also, the depressed group
      reported engaging in less rational processing and in more maladaptive
      experiential processing in everyday life than did the control group.

PMID- 9569660
TI  - The structure of self-concept in female preadolescent twins: a behavioral genetic
      approach.
AB  - Two hundred and forty-three female monozygotic (MZ) and 164 female dizygotic (DZ)
      twin pairs, aged 11 and 12 years, who participated in the ongoing Minnesota Twin
      Family Study, completed six specific scales of the Piers-Harris Children's Self
      Concept Scale (P-H). Model-fitting analyses yielded three major conclusions.
      First, approximately 30% of the variance in specific self-concepts in female
      preadolescents was due to genetic factors, with the remaining variance being
      accounted for primarily by nonshared environmental factors and measurement error.
      Second, the underlying common genetic, shared environmental, and nonshared
      environmental factors influenced specific facets of self-concept directly and
      independently, rather than through an intervening phenotypic general self
      concept. Finally, whereas genetic, shared environmental, and nonshared
      environmental factors were necessary to explain the commonality among the
      specific self-concept scales, only genetic and nonshared environmental factors
      were sufficient to explain the specificity of those scales.

PMID- 9569661
TI  - Personality prototypes and ego development: conceptual similarities and relations
      in adult women.
AB  - Three studies investigated how three personality prototypes (K. York & O.P. John,
      1992) relate to J. Loevinger's (1976) stages of ego development (ED). Study 1
      examined their conceptual similarities, and Study 2 their relations in a sample
      of adult women. In both studies, the personality prototypes mapped onto regions
      defined by multiple ED stages: The Individuated prototype was most likely to
      reach the high region of ED (Individualistic, Autonomous, and Integrated); the
      Traditional prototype was most likely to function in the middle region
      (Conformist, Self-aware, and Conscientious); and the Conflicted prototype was
      more likely to remain in the low region (Impulsive and Self-protective). In
      addition to these between-prototype differences, Study 3 explored whether
      differences in life outcomes within the prototypes are also related to ED;
      findings suggest that personality prototype and ego development may interact in
      shaping the life course.

PMID- 9569662
TI  - A trial to compare the effects of pH, buffer concentration, and NaCl, on one
      fluorescent and two bioluminescent bacterial tests for acute toxicity.
AB  - Of all the bioassays to determine acute toxicity described in the literature,
      those that employ bacteria as indicator organisms are usually the most rapid and
      the most economic, although alone they cannot predict the possible toxic effect
      of any type of substance. When bioassays are employed to test the toxicity of
      known substances and of compounds in samples from waste discharges they have to
      work in very different conditions from those for which they are designed. The
      effects of three factors, pH, buffer concentration, and NaCl, on the performance
      of a fluorogenic bioassay based on the beta-glucuronidase activity of Escherichia
      coli were investigated. The results of this test were compared with those of two
      known biluminescent bacteria tests. The fluorogenic bioassay has a more
      restricted optimum pH range, while the influence of buffer concentration was
      similar for the three tests. E. coli glucuronidase activity was affected at a
      concentration as low as 128 mg/l of NaCl. Changes in the pH or buffer
      concentrations or chloride ions, greatly influenced the respectives toxicities of
      four substances, acridine orange, TEMED, 2-mercaptoethanol, and mercuric
      chloride.

PMID- 9569663
TI  - Molecular cloning and characterization of the gene encoding 53 kD outer membrane
      protein of Porphyromonas gingivalis.
AB  - The pga53 gene which encoded the antigenic 53 kD outer membrane protein (Ag53)
      was isolated from a genomic DNA library of Porphyromonas gingivalis FDC381 by
      using an Ag53-immunized rabbit serum. Determination of its complete nucleotide
      sequence revealed that the precursor of Ag53 had a 50 amino-acid putative signal
      sequence and the mature protein of 448 amino acids. The deduced amino acid
      sequence after a 50 amino-acid putative signal sequence was in complete agreement
      with the first 20 N-terminal amino acids of purified Ag53. Analysis of the
      deduced amino acid sequence revealed the presence of a highly hydrophilic proline
      rich region at the C-terminal of Ag53. The deduced amino acid sequence showed
      29.9% homology with that of a 72 kD cell-surface protein in P. gingivalis.
      Southern hybridization revealed that pga53 was specific to several P. gingivalis
      strains and that P. gingivalis strains which did not possess Ag53 had genes
      homologous to pga53.

PMID- 9569664
TI  - Pleistocene phylogeographic effects on avian populations and the speciation
      process.
AB  - Pleistocene biogeographic events have traditionally been ascribed a major role in
      promoting speciations and in sculpting the present-day diversity and
      distributions of vertebrate taxa. However, this paradigm has recently come under
      challenge from a review of interspecific mtDNA genetic distances in birds: most
      sister-species separations dated to the Pliocene. Here we summarize the
      literature on intraspecific mtDNA phylogeographic patterns in birds and
      reinterpret the molecular evidence bearing on Pleistocene influences. At least 37
      of the 63 avian species surveyed (59%) are sundered into recognizable
      phylogeographic units, and 28 of these separations (76%) trace to the
      Pleistocene. Furthermore, use of phylogroup separation times within species as
      minimum estimates of 'speciation durations' also indicates that many protracted
      speciations, considered individually, probably extended through time from
      Pliocene origins to Pleistocene completions. When avian speciation is viewed
      properly as an extended temporal process rather than as a point event,
      Pleistocene conditions appear to have played an active role both in initiating
      major phylogeographic separations within species, and in completing speciations
      that had been inaugurated earlier. Whether the Pleistocene was exceptional in
      these regards compared with other geological times remains to be determined.

PMID- 9569665
TI  - Characterization and function of carbonic anhydrases in the zooxanthellae-giant
      clam symbiosis.
AB  - Carbonic anhydrase (CA) has been purified from the host tissue of Tridacna gigas,
      a clam that lives in symbiosis with the dinoflagellate alga, Symbiodinium. At
      least two isoforms of CA were identified in both gill and mantle tissue. The
      larger (70 kDa) isoform is a glycoprotein with both N- and O-glycans attached and
      has highest homology to CAII. It is associated with the membrane fraction while
      the smaller (32 kDa) is present in the aqueous phase in both tissues. The 32 kDa
      CA has high homology with mammalian CAI at the N-terminus. Both isoforms cross
      reacted with antibodies to CAII from chicken. Immunohistology demonstrated that
      the 70 kDa CA is present within the ciliated branchial filaments and cells lining
      the tertiary water channels in the gills of T. gigas. This is consistent with a
      role in the transport of inorganic carbon (Ci) to the haemolymph and therefore
      supply of Ci to the zooxanthellae. CA was also detected in mantle epithelial
      cells where it may also contribute to Ci supply to the zooxanthellae. The hyaline
      body and nerve tissue in the mantle express the 70 kDa CA where it may be
      involved in light sensing and nervous transmission.

PMID- 9569666
TI  - Comparison of articulate brachiopod nuclear and mitochondrial gene trees leads to
      a clade-based redefinition of protostomes (Protostomozoa) and deuterostomes
      (Deuterostomozoa)
AB  - Nuclear and mtDNA sequences from selected short-looped terebratuloid
      (terebratulacean) articulate brachiopods yield congruent and genetically
      independent phylogenetic reconstructions by parsimony, neighbour-joining and
      maximum likelihood methods, suggesting that both sources of data are reliable
      guides to brachiopod species phylogeny. The present-day genealogical
      relationships and geographical distributions of the tested terebratuloid
      brachiopods are consistent with a tethyan dispersal and subsequent radiation.
      Concordance of nuclear and mitochondrial gene phylogenies reinforces previous
      indications that articulate brachiopods, inarticulate brachiopods, phoronids and
      ectoprocts cluster with other organisms generally regarded as protostomes. Since
      ontogeny and morphology in brachiopods, ectoprocts and phoronids depart in
      important respects from those features supposedly diagnostic of protostomes, this
      demonstrates that the operational definition of protostomy by the usual
      ontological characters must be misleading or unreliable. New, molecular,
      operational definitions are proposed to replace the traditional criteria for the
      recognition of protostomes and deuterostomes, and the clade-based terms
      'Protostomoza' and 'Deuterostomozoa' are proposed to replace the existing term
      'Protostomia' and 'Deuterostomia'.

PMID- 9569667
TI  - Microsatellites reveal heterosis in red deer.
AB  - The fitness consequences of inbreeding and outbreeding are poorly understood in
      natural populations. We explore two microsatellite-based variables, individual
      heterozygosity (likely to correlate with recent inbreeding) and a new individual
      specific internal distance measure, mean d2 (focusing on events deeper in the
      pedigree), in relation to two measures of fitness expressed early in life, birth
      weight and neonatal survival, in 670 red deer calves (Cervus elaphus) born on the
      Isle of Rum between 1982 and 1996. For comparison, we also analyse inbreeding
      coefficients derived from pedigrees in which paternity was inferred by molecular
      methods. Only 14 out of 231 calves (6.1%) had non-zero inbreeding coefficients,
      and neither inbreeding coefficient nor individual heterozygosity was consistently
      related to birth weight or neonatal survival. However, mean d2 was consistently
      related to both fitness measures. Low mean d2 was associated with low birth
      weight, especially following cold Aprils, in which foetal growth is reduced. Low
      mean d2 was also associated with low neonatal survival, but this effect was
      probably mediated by birth weight because fitting birth weight to the neonatal
      survival model displaced mean d2 as an explanatory variable. We conclude that in
      the deer population fitness measures expressed early in life do not show evidence
      of inbreeding depression, but they do show evidence of heterosis, possibly as a
      result of population mixing. We also demonstrate the practical problems of
      estimating inbreeding via pedigrees compared with a direct marker-based estimate
      of individual heterozygosity. We suggest that, together, individual
      heterozygosity and mean d2, estimated using microsatellites, are useful tools for
      exploring inbreeding and outbreeding in natural population.

PMID- 9569668
TI  - Male courtship song frequency as an indicator of male genetic quality in an
      insect species, Drosophila montana.
AB  - Most theoretical models on evolution of male secondary sexual characters and
      female preferences for these characters suggest that the male characters evolve
      in response to female preferences that may themselves evolve in response to
      direct or indirect benefits of choice. In Drosophila montana (a species of the D.
      virilis group), females use male song in their mate choice, preferring males that
      produce songs with short sound pulses and a high carrier frequency. We
      demonstrate here that the females get indirect benefits from their choice: in our
      data the frequency of the male song correlated with the survival rate of the
      male's progeny from egg to adulthood (indirect benefit for the female), but not
      with the fecundity of his mating partner (no direct benefit for the female). Male
      wing centroid asymmetry did not correlate with male wing song characters, nor
      with female egg production nor the fitness of her progeny, suggesting that
      fluctuating asymmetry in male wings does not play a major role in sexual
      signalling. The fact that the male song gives the female information on the
      male's condition/genetic quality in D. montana suggests that in this species the
      evolution of female preferences for male song characters could have evolved
      through condition-dependent viability selection presented in some 'good genes'
      models.

PMID- 9569669
TI  - Phylogeny and PCR-based classification of Wolbachia strains using wsp gene
      sequences.
AB  - Wolbachia are a group of intracellular inherited bacteria that infect a wide
      range of arthropods. They are associated with a number of different reproductive
      phenotypes in their hosts, such as cytoplasmic incompatibility, parthenogenesis
      and feminization. While it is known that the bacterial strains responsible for
      these different host phenotypes form a single clade within the alpha
      Proteobacteria, until now it has not been possible to resolve the evolutionary
      relationships between different Wolbachia strains. To address this issue we have
      cloned and sequenced a gene encoding a surface protein of Wolbachia (wsp) from a
      representative sample of 28 Wolbachia strains. The sequences from this gene were
      highly variable and could be used to resolve the phylogenetic relationships of
      different Wolbachia strains. Based on the sequence of the wsp gene from different
      Wolbachia isolates we propose that the Wolbachia pipientis clade be initially
      divided into 12 groups. As more sequence information becomes available we expect
      the number of such groups to increase. In addition, we present a method of
      Wolbachia classification based on the use of group-specific wsp polymerase chain
      reaction (PGR) primers which will allow Wolbachia isolates to be typed without
      the need to clone and sequence individual Wolbachia genes. This system should
      facilitate future studies investigating the distribution and biology of Wolbachia
      strains from large samples of different host species.

PMID- 9569670
TI  - Effects of a circadian mutation on seasonality in Syrian hamsters (Mesocricetus
      auratus).
AB  - In Syrian hamsters, exposure to short photoperiods or constant darkness induces a
      decrease in gonadotrophin secretion and gonadal regression. After 10-12 weeks,
      animals undergo spontaneous gonadal reactivation, gonadotrophin concentrations
      rise, and in males, testes size increases and spermatogenesis resumes. The tau
      mutation shortens the period of circadian wheel-running activity by 4 h in the
      homozygote. Here, we examine the impact of this mutation on the reproductive
      response to photoperiod change. Seventeen adult tau mutant and nine adult wild
      type males were housed in complete darkness for 25 weeks and testes size
      determined at weekly intervals. Gonadal regression and subsequent recrudescence
      occurred in both groups of animals. Regression occurred more rapidly in tau
      mutants, with a nadir significantly earlier than wild-types but after a similar
      number of circadian cycles. Rates of testicular recrudescence were similar in
      both groups. Our data suggest that an acceleration of the circadian period
      increases the rate of reproductive inhibition in animals exposed to inhibitory
      photoperiods. Once initiated, the rate of spontaneous reactivation may be
      independent of the circadian axis.

PMID- 9569671
TI  - Dynamics of T-cell antagonism: enhanced viral diversity and survival.
AB  - In rapidly evolving viruses the detection of virally infected cells can possibly
      be subverted by the production of altered peptides. There are peptides with
      single amino acid changes that can dramatically change T-cell responses, e.g. a
      loss of cytotoxic activity. They are still recognized by the T cell, but the
      signals required for effector function are only partially delivered. Thus,
      altered peptide presenting cells can act as decoy targets for specific immune
      responses. The existence of altered peptides in vivo has been demonstrated in
      hepatitis B and HIV. Using a mathematical model we address the question of how
      these altered peptides can affect the virus-immune system dynamics, and
      demonstrate that virus survival is enhanced. If the mutation rate of the virus is
      sufficient, one observes complex dynamics in which the antagonism acts so as to
      maintain the viral diversity, possibly leading to the development of a mutually
      antagonistic network or a continual turnover of escape mutants. In either case
      the pathogen is able to outrun the immune system. Indeed, sometimes the
      enhancement is so great that a virus that would normally be cleared by the immune
      system is able to outrun it.

PMID- 9569673
TI  - Taking aim at tumors.

PMID- 9569674
TI  - Experimental surgery. When less is more.

PMID- 9569672
TI  - Task-specific impairments and enhancements induced by magnetic stimulation of
      human visual area V5.
AB  - Transcranial magnetic stimulation (TMS) can be used to simulate the effects of
      highly circumscribed brain damage permanently present in some neuropsychological
      patients, by reversibly disrupting the normal functioning of the cortical area to
      which it is applied. By using TMS we attempted to recreate deficits similar to
      those reported in a motion-blind patient and to assess the specificity of
      deficits when TMS is applied over human area V5. We used six visual search tasks
      and showed that subjects were impaired in a motion but not a form 'pop-out' task
      when TMS was applied over V5. When motion was present, but irrelevant, or when
      attention to colour and form were required, TMS applied to V5 enhanced
      performance. When attention to motion was required in a motion-form conjunction
      search task, irrespective of whether the target was moving or stationary, TMS
      disrupted performance. These data suggest that attention to different visual
      attributes involves mutual inhibition between different extrastriate visual
      areas.

PMID- 9569675
TI  - The genetics of cognitive abilities and disabilities.

PMID- 9569677
TI  - Serous cutaneous glands in Phyllomedusa hypochondrialis (Anura, Hylidae):
      secretory patterns during ontogenesis.
AB  - Three syncytial gland types (Ia, Ib, and II ) have been described in the skin of
      larval, juvenile and adult Phyllomedusa hypochondrialis, which share the
      ultrastructural traits common to the serous secretory units of anuran skin,
      although each manufactures a peculiar product. Type la secretion consists of
      dense granules provided with a peculiar substructure, type Ib of vesicles holding
      a lucent material, type II of lipid deposits. None of the developmental stages
      investigated showed intermediate features between any of the three cutaneous
      products, which accumulate in the syncytial cytoplasms of the secretory units
      following different biosynthetic pathways, consistent with each gland type. These
      findings confirm previous results on adult specimens of P. hypochondrialis and P.
      sauvagei and stress the polymorphism of the serous glands in the genus
      Phyllomedusa. This morphological variability reflects the wide adaptive
      flexibility of serous glands in anurans.

PMID- 9569676
TI  - Isolation and culture of epithelial cells from rat ductuli efferentes and initial
      segment epididymidis.
AB  - To improve the study of epithelial function in rat ductuli efferentes (efferent
      ductules) and initial segment epididymis, we developed a primary cell culture
      system with modification of the Klinefelter method (1992). The cultured efferent
      ductal epithelium was grown to confluence and the cells maintained many of the
      organelles characteristic of these cells in vivo, including dense-staining
      granules, indented nuclei and apical cilia. Ciliary beat was observed for up to
      10 days in culture, Cultured initial segment epithelial cells were elongated and
      characterized by apical branched microvilli. Electron microscopy revealed intact
      cell junctions, and endocytotic apparatus and lysosomal granules.
      Ultrastructurally, the initial segment epithelium contained a well developed
      Golgi apparatus. For both epithelia, cell characteristics were also confirmed by
      indirect immunofluorescent staining for cytokeratins 8, 18. Endocytotic activity
      was detected by the uptake of cationic ferritin at the apical surface and within
      vesicles. Estrogen receptor and clusterin mRNAs were expressed in the cultured
      epithelia and no difference was found in their expressions when cultured with or
      without 10(-9)M 17-beta estradiol. Indirect immunofluorescent staining for
      clusterin further indicated that this protein was present in the cultures. In
      conclusion, these in vitro methods will be useful for the investigation of
      epithelial function in the head of the epididymis.

PMID- 9569678
TI  - An endocrine brain? The pattern of FMRF-amide immunoreactivity in Acoela
      (Plathelminthes).
AB  - In order to solve the problem of whether the Acoela have a brain of a common
      flatworm type, an immunocytochemical study was performed of the pattern of FMRF
      amide in the nervous system of four species of Acoela, Anaperus biaculeatus,
      Childia groenlandica, Antinoposthia beklemischevi and Mecynostomum sp. In all
      species a FMRF-amide positive bilobed brain-like structure lacking neuropile was
      observed. This brain is composed of large multipolar nerve cells with short
      processes. The FMRF-amide immunoreactivity appears as spots in the cytoplasm.
      Short lateral branches originating from the periphery of the brain were observed
      in Anaperus biaculeatus. No immunoreactive nerve cords were detected. The results
      indicate that the brain-like structure of Acoela is not homologous with the
      brains of other Plathelminthes and implies an independent evolution of Acoela.

PMID- 9569679
TI  - The effect of chronic luteinizing hormone treatment on adult rat Leydig cells.
AB  - We investigated the chronic effects of luteinizing hormone (LH) treatment on
      adult rat Leydig cell structure and function. Two groups of sexually mature male
      Sprague-Dawley rats were used; controls and rats implanted subdermally with LH
      filled Alzet miniosmotic pumps (delivers 24 micrograms of LH per day). After 2
      weeks of LH treatment, testes of these rats were fixed by 2.5% glutaraldehyde in
      cacodylate buffer and processed and embedded in epon-araldite for light and
      electron microscopy and electron microscopic immunocytochemistry. Using light
      microscopic stereology, Leydig cell volume density, number of Leydig cells per
      testis, and the average volume of a Leydig cell were determined. Additionally,
      the organelle volumes per Leydig cells were quantified by electron microscopic
      stereology. Sterol carrier protein-2 (SCP2) and catalase in Leydig cells were
      immunolocalized via the Protein A gold method. Isolated and purified Leydig cells
      were used to determine the LH-stimulated (100 ng/ml) testosterone secretory
      capacity per Leydig cell in vitro and to compare the SCP2 and catalase content in
      equal numbers of Leydig cells using immunoblot analysis. After 2 weeks of LH
      treatment, Leydig cell number per testis and the average volume showed a two-fold
      increase. All organelles tested, except the lipid droplets, were significantly (P
      < 0.05) increased two-fold in volume per Leydig cell. Testosterone secretory
      capacity per Leydig cell was increased approximately six-fold in the LH-treated
      group. Immunolabeling studies showed that the intraperoxisomal SCP2 content was
      significantly greater (P < 0.05) and the catalase content was significantly lower
      (P < 0.05) in LH-treated rats compared to to controls. Immunoblots showed that
      the total SCP2 content per cell is greater and the catalase content per cell is
      similar in Leydig cells of LH-treated rats compared to controls. In summary,
      chronic LH treatment produced hyperplasia, hypertrophy and increased testosterone
      secretory capacity in leydig cells of adult rats. However, the increase in the
      testosterone secretory capacity per Leydig cell exceeds the degree of Leydig cell
      hypertrophy, which cannot be explained by a generalized increase in volumes of
      all Leydig cell organelles in the LH-treated rats. These results also suggested
      that chronic LH treatment induces differential synthesis of peroxisomal proteins,
      i.e. an increase in SCP2 synthesis and no change in catalase synthesis. This
      resulted in peroxisomes rich in SCP2 and lower in catalase. Significance of these
      effects in relation to the increased steroidogenic capacity of Leydig cells
      remains to be determined.

PMID- 9569681
TI  - Endocrine and neuroendocrine effects of Azadirachtin in adult females of the
      earwig Labidura riparia.
AB  - In previous studies we have shown that injection of the insect growth regulator
      Azadirachtin (AZA) into young vitellogenic females induces inhibition of
      vitellogenesis in a dose-dependent manner. Juvenile hormone treatment rescues
      vitellogenin synthesis and ovarian growth. The cytopathological effects on
      ovaries and fat body are not linked to an inhibition of feeding. In this work we
      investigated the effects of AZA on the endocrine and neuroendocrine system.
      Enzyme immunoassay reveals that ovarian ecdysteroid levels are drastically
      reduced, in a dose-dependent fashion, by AZA. Ultrastructural study indicates
      that corpus allatum cells exhibit signs of inactivity and degenerative changes
      after AZA exposure. Using an antibody against allastostatin-3 of Blatella
      germanica (BLAST-3), we show the appearance of strong immunoreactivity of
      numerous cells and axons in the brain of AZA-injected females. We conclude that
      vitellogenesis inhibition by AZA consists of a direct cytotoxic effect as well as
      a generalized disruption of endocrine and neuroendocrine functions.

PMID- 9569680
TI  - Postembryonic development of leucokinin-like immunoreactive neurons in the moth
      Spodoptera litura.
AB  - Antiserum to leucokinin I, a neuropeptide originally isolated from the cockroach
      Leucophaea maderae, was used for immunocytochemical labeling of neurons in the
      brain and ventral ganglia of the moth Spodoptera litura during postembryonic
      development. In the ventral ganglia, leucokinin-like immunoreactivity begins to
      occur in the abdominal ganglion A3 to A7 of first instar larva. One to two weakly
      labeled pairs of bilateral LK-LI cell bodies are located in the subesophageal
      ganglion of fourth to sixth instar larvae and in the abdominal ganglia A1 to A7
      of second to sixth instar larvae. The abdominal ganglion A1 of fourth to sixth
      instar larvae and A8 of sixth instar larva each contain one weakly labeled pair
      of median LK-LI cell bodies. Two strongly labeled pairs of bilateral LK-LI
      neurons are found in A3 to A7 of third to sixth instar larvae. Abdominal ganglia
      A1 to A8 of prepupa, pupa and adult contain one to three weakly labeled pairs of
      bilateral LK-LI neurons. Two strongly labeled pairs of bilateral LK-LI neurons in
      each of the abdominal ganglia of larva, prepupa, pupa and adult send axons to the
      neuropil, and then each axon bifurcates into two axonal branches. Theses axonal
      branches from two bundles. From each of the two pairs of neurons an axon exits
      through the posterior ventral nerve (N2) which runs to the transverse nerve of
      the next posterior segment. In larval brains, 2-16 pairs of bilateral LK-LI cell
      bodies can be found together with LK-LI processes in the central neuropil. The
      larval brains show large changes in the number of LK-LI neurons throughout
      postembryonic development. The number of LK-LI cell bodies are reduced in number
      from sixth instar larval brain. Therefore, prepupal, pupal and adult brains
      contain a smaller number of LK-LI cell bodies. Two pairs of LK-LI median
      neurosecretory cells located immediately beside the pars intercerebralis in
      larval brains increase to three pairs in the 7-day-old pupal brain. In the adult,
      however, LK-LI median neurosecretory cells decrease to one pair.

PMID- 9569682
TI  - Biological behavior and cell properties of new AKR lymphoma malignancy variants.
AB  - The AKR lymphoma-leukemia is a T lymphocyte neoplasm, most suitable as a model
      for human T cell malignancies. We have been interested in the process of tumor
      progression in the AKR lymphoma system. In the present study, two newly isolated
      variants, the TAU-42 and TAU-44, were characterized with respect to their
      biological behavior, by comparing them to a previously studied low-malignancy
      variant, the TAU-39. While the TAU-44 variant formed large s.c. local tumors, the
      TAU-42 variant formed only small growths or none at all. The TAU-42 lymphoma was
      found to have the highest malignant potential: it displayed very marked
      dissemination to spleen, lymph nodes, liver and lungs. The TAU-44 variant had an
      intermediate degree of metastatic potential but presented a predilection for
      spread to lymph nodes and spleen and was sometimes found to metastasize to
      peculiar organs, such as heart and pancreas. Cells derived from the different
      lymphoma variants varied in their immunophenotype: the highly malignant variant
      cells expressed more CD4 antigen than the low-malignancy one. The opposite was
      observed with regard to CD8. The variant cells also differed in their migrating
      capacity, the more malignant one exhibiting a higher motile activity. Studies on
      the tumor progression model of AKR lymphoma might contribute to the elucidation
      of the features determining the aggressiveness of T lymphocytic malignancies.

PMID- 9569683
TI  - Effects of castration on the lymphocytes of the thymus, spleen and lymph nodes.
AB  - It is well known that the thymus plays an important role in the development and
      maintenance of a competent immune system. The thymus atrophies with age, a
      process that is accelerated after puberty when there is elevation of serum sex
      steroid levels. We have used a panel of commercial monoclonal antibodies against
      various T and B cell surface markers to investigate the post-castration
      histological alterations in the thymus, spleen and lymph nodes of male Sprague
      Dawley rats. Castration of 5-week-old male rats produced a significant increase
      in thymic weight (P < 0.05) compared to age-matched intact animals. The major
      observations from the immunohistochemical studies were post-castration elevations
      in staining for total T cells (MRC OX 19 and W 3/13), CD8 cells (MRC OX 8), B
      cells (MRC OX 12 and MARK-1) and cells bearing activation markers such as IL-2
      receptor (MRC OX 39), transferrin receptor (MRC OX 26) and major
      histocompatibility class II antigen (MRC OX 6). These data suggest that following
      castration there is an increase in the ability of lymphocytes to respond to
      activation. As a result, there are elevated numbers of immature thymocytes within
      the thymus that undergo differentiation/maturation and consequently produce an
      increase in peripheral T and B cells.

PMID- 9569684
TI  - Use of rotary shadowing electron microscopy to investigate the collagen fibrils
      in the extracellular matrix of cuttle-fish (Sepia officinalis) and chicken
      cartilage.
AB  - Collagen fibrils isolated from sternal cartilage of chick embryo and
      chondrocranium of cuttle-fish (Sepia officinalis) were examined with the electron
      microscope after rotary showing. The aim was to determine whether collagen
      fibrils from S. officinalis cartilage contained collagen molecules similar to the
      type IX collagen of vertebrate cartilage. Cartilage from both sources presented a
      highly variable appearance and only occasionally did preparations contain fibrils
      having the structure described by Vaughan et al. (1988) for vertebrate cartilage.
      Subsequent electron microscope investigation of collagen samples during the
      various stages of fibril preparation showed that the method did not yield
      reproducible results, and that is altered the morphology of the isolated
      structures. It was not, therefore, possible to confirm the hypothesis that
      collagen molecules with a morphology similar to that type IX vertebrate collagen
      are a component of the extracellular matrix of cephalopod cartilage.

PMID- 9569685
TI  - Expression of smooth muscle caldesmon in developing chicken gizzard.
AB  - Caldesmon is an actin/calmodulin/tropomyosin protein located in the thin
      filaments of smooth muscle cells and microfilaments of nonmuscle cells. Two
      isoforms of caldesmon, h- and l-types, shown to exist in vertebrate smooth and
      nonmuscle cells respectively, are produced by alternative splicing of the
      caldesmon mRNA encoded by a single gene. To study the expression of smooth muscle
      specific h-caldesmon during the differentiation of mesenchymal cells into smooth
      muscle cells, soluble protein and total RNA from the gizzard primordium in the
      gut region of 5-day and gizzards of 7-, 9-, 13-, 17- and 21-day embryos and 2
      days post-hatch chicks were extracted and analyzed for caldesmon expression at
      both protein and mRNA levels. Western blot analysis of proteins and
      immunofluorescence microscopy of tissue section were carried out using an
      antibody specific for h-caldesmon. Total RNA was analyzed by Northern blotting
      using a caldesmon cDNA probe, and h- and l-caldesmon cDNAs were identified due to
      the difference in their molecular sizes (4.8 and 4.1 kb respectively). The mRNA
      was also analyzed by reverse transcribed-polymerase chain reaction (RT-PCR) and
      Southern blot analysis. Our results show that the I-caldesmon mRNA was expressed
      at higher levels in the gizzard primordium during the early stages of
      development, and decreased gradually during growth. The h-caldesmon protein and
      mRNA, not expressed at day 5, is minimally expressed at day 7 and is fully turned
      on by day 9. Additionally, sequence analyses of the RT-PCR products of I
      caldesmon showed that it lacked the spacer region, as predicted. RT-PCR analysis
      of total RNA gave two h-caldesmon fragments. These two fragments were identified
      as two different isoforms of h-caldesmon since they both contained the spacer
      region. They also showed homology in the region of exon 4 had differences in the
      region of exon 3b.

PMID- 9569686
TI  - Continuous subendothelial network formed by pericyte-like cells in human vascular
      bed.
AB  - The localization of pericyte-like cells in adult human vascular bed was studied
      immunocytochemically using anti-pericyte antibody--3G5. In large, medium- and
      small-size arteries, pericyte-like cells were identified in the inner intimal
      layer, predominantly in the subendothelium, in the outer layer of the media and
      in the adventitia in vasa vasora. In veins, pericytes were found in the
      subendothelial layer of the intima, in the media and in the adventitia where they
      were located in vasa vasora. These cells were revealed in the subendothelium of
      arterioles, venules and capillaries of the pia mater encephali. Examination of
      intimal en face preparations of various size blood vessels showed that
      subendothelial pericyte-like cells form a network contacting with their
      processes. Thus we found a continuous subendothelial network formed by pericyte
      like cells in the human vascular bed.

PMID- 9569687
TI  - Evaluation of DNA preparation techniques for detection of the SLT-1 gene of
      Escherichia coli O157: H7 in bovine faeces using the polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) has the potential to detect low levels of the
      human pathogen Escherichia coli O157: H7 in bovine faeces. To improve the utility
      of PCR for this application, several methods for preparing template DNA from
      bovine faeces, both directly and after non-selective enrichment, were tested.
      These were boiling, enzyme treatment, enzyme treatment plus phenol-chloroform
      extraction, and enzyme treatment plus phenol-chloroform extraction plus Geneclean
      purification. Of these, the boiling method was the most consistent and had a
      sensitivity of approximately 3 cfu g-1 faeces, with an assay time of less than 32
      h. The boiling method was also combined with immunomagnetic separation (IMS) to
      detect E. coli O157: H7 in less than 8 h, but with a sensitivity of approximately
      10(3) cfu g-1 faeces. These methods can be used to prepare template for PCR
      screening of bovine faeces using any appropriate PCR primers.

PMID- 9569688
TI  - Degradation of geosmin-like compounds by selected species of gram-positive
      bacteria.
AB  - Biodegradation of geosmin produced by Streptomyces halstedii (A-1 strain) was
      investigated using seven Gram-positive bacteria. Bacterial action on the A-1
      extract was followed at 15, 45 and 120 min. Bacillus cereus ssp. thuringiensis HD
      1, B. cereus 3711 and B. cereus ssp. mycoides 4379 showed no effect. However,
      Arthrobacter atrocyaneus, Arth. globiformis, Chlorophenolicus N-1053 and
      Rhodococcus maris caused a colour change from blue to yellow (positive reaction).
      These data suggest that geosmin can be degraded by specific species of Gram
      positive bacteria. Biodegradation of geosmin, which causes bad odour in drinking
      water, can be used as a new technology in water treatment.

PMID- 9569689
TI  - Improved cloning vectors for Bifidobacterium spp.
AB  - The recombinant plasmids pDLI41, pDGA7 and pDCO7 were constructed by cloning in
      pDG7, a vector based on Bifidobacterium longum replicon pMB1, the following
      heterologous genes: Pseudomonas fluorescens lipase, Bacillus licheniformis alpha
      amylase and Streptomyces sp. cholesterol oxidase. The hybrid plasmids efficiently
      transformed Bifidobacterium belonging to five different species. A novel
      Escherichia coli-Bifidobacterium set of shuttle vectors based on the replicon
      pMB1 (pLF5, pCLJ15, pSPEC1) featuring chloramphenicol, erythromycin and
      spectinomycin resistance genetic determinants as selection marker for
      bifidobacteria, was developed. The plasmid pTRE3, a derivative of pLF5, was the
      smallest (2.8 kb) Bifidobacterium vector, possessed a convenient multicloning
      site and presented high structural and segregational stability.

PMID- 9569690
TI  - Pulsed-field gel electrophoresis typing of Hafnia alvei isolated from chub-packed
      and retail ground beef.
AB  - Thirty-eight isolates of Hafnia alvei were characterized by biochemical profiles,
      ribotyping and pulsed-field gel electrophoresis (PFGE) patterns. The isolates
      were recovered from chub-packed (19 isolates) or retail (nine isolates) ground
      beef, or were obtained from culture repositories (10 isolates). Biochemical
      profiling differentiated the 38 isolates into five groups and a commercial
      ribotyping method recognized 11 groups, whereas PFGE differentiated the same 38
      isolates into 19 groups. These data substantiate that PFGE is a highly
      discriminatory tool for establishing the relatedness among Hafnia alvei strains.

PMID- 9569691
TI  - Occurrence and distribution of Vibrio vulnificus in tropical fish and shellfish
      from Cochin (India).
AB  - The incidence and distribution of Vibrio vulnificus in marine and brackish-water
      fish and shellfish from coastal areas of Cochin on the west coast of India were
      studied. For marine fish collected in very fresh condition from vessels, a level
      of incidence of 16.6% was noted. Frequency of isolation was greater from the
      intestine than from the muscle. The greater Most Probable Number (MPN) count
      determined by the three tube method ranged from 15 to 910 g-1 in the positive
      samples.

PMID- 9569692
TI  - Molecular characterization of a strain-specific sequence in Campylobacter jejuni.
AB  - Campylobacter jejuni strains 81116 and NCTC 11392 were shown to contain a region
      of DNA that was not present in other strains. This region was cloned from the
      chromosome of strain 81116 and the nucleotide sequence determined. It was found
      to contain an insert of 742 bp which was flanked by direct repeats of 45 bp.
      Although the nature of this sequence is unknown at present, it is clear that it
      only presents in certain strains of Camp. jejuni and it may therefore be useful
      as an epidemiological tool.

PMID- 9569693
TI  - Antimicrobial properties of plant essential oils and essences against five
      important food-borne pathogens.
AB  - The antimicrobial properties of 21 plant essential oils and two essences were
      investigated against five important food-borne pathogens, Campylobacter jejuni,
      Salmonella enteritidis, Escherichia coli, Staphylococcus aureus and Listeria
      monocytogenes. The oils of bay, cinnamon, clove and thyme were the most
      inhibitory, each having a bacteriostatic concentration of 0.075% or less against
      all five pathogens. In general, Gram-positive bacteria were more sensitive to
      inhibition by plant essential oils than the Gram-negative bacteria. Campylobacter
      jejuni was the most resistant of the bacteria investigated to plant essential
      oils, with only the oils of bay and thyme having a bacteriocidal concentration of
      less than 1%. At 35 degrees C, L. monocytogenes was extremely sensitive to the
      oil of nutmeg. A concentration of less than 0.01% was bacteriostatic and 0.05%
      was bacteriocidal, but when the temperature was reduced to 4 degrees, the
      bacteriostatic concentration was increased to 0.5% and the bacteriocidal
      concentration to greater than 1%.

PMID- 9569694
TI  - Susceptibility of bifidobacteria to nisin.
AB  - A collection of 17 bifidobacteria was tested for sensitivity or resistance to
      lantibiotic nisin. Minimal inhibitory concentration of the strain tested was
      highly variable, ranging from 4.88 to 10,000 IU-1. In general, strains isolated
      from faecal samples were more resistant than those purchased from culture
      collections. These results could be useful in the production of foods containing
      both bifidobacteria and nisin.

PMID- 9569695
TI  - Development and evaluation of polymerase chain reaction tests as an aid to
      diagnosis of swine dysentery and intestinal spirochaetosis.
AB  - Polymerase chain reaction (PCR) tests were established for detection of Serpulina
      hyodysenteriae, the agent of swine dysentery, and S. pilosicoli, the agent of
      intestinal spirochaetosis. Both reactions were specific when tested with DNA from
      107 strains of various intestinal spirochaetes. For diagnostic use, faeces were
      plated to selective medium, and diatomaceous earth extraction used to obtain DNA
      prior to PCR. This procedure detected 10(3)-10(4) cells of either organism seeded
      into 0.2 g of faeces. When applied to 63 samples from pigs of eight piggeries
      naturally infected with either S. hyodysenteriae or S. pilosicoli, both PCRs were
      specific, more rapid, and detected more positive samples than did routine faecal
      culture and isolation.

PMID- 9569696
TI  - High-resolution genotyping of Salmonella strains by AFLP-fingerprinting.
AB  - High resolution AFLP fingerprinting, in which subsets of genomic restriction
      fragments are amplified by means of PCR, was used for the identification of
      different. Salmonella serotypes to investigate whether this technique is
      applicable in epidemiological studies. Seventy-eight different Salmonella strains
      comprising 62 serotypes were genetically identified by AFLP. Primer combination
      M00 (MseI primer without additional 3' nucleotides) and E11 (EcoRI primer with
      two additional 3' nucleotides) resulted in reproducible profiles containing
      approximately 50 bands. All serotypes were characterized by a unique profile. In
      addition, AFLP fingerprinting enabled phage type identification. Different
      strains previously identified as identical, using typing methods with lower
      resolution, could be distinguished, showing that AFLP fingerprinting is well
      suited for bacterial epidemiology and identification.

PMID- 9569697
TI  - Galacto-oligosaccharide production using a recycling cell culture of
      Sterigmatomyces elviae CBS8119.
AB  - Addition of small amounts of Fe2+, Zn2+, Cu2+ and thiamine-HCL to the culture
      medium was required for promoting the galactooligosaccharide (Gal-OS)-producing
      activity of Sterigmatomyces elviae CBS8119, when the concentration of yeast
      extract in the medium was lowered to 0.1 g l-1. Galactooligosaccharide production
      using a recycling cell culture was performed in a medium containing 360 mg ml-1
      of lactose supplemented with optimal concentrations of Fe2+ (1.5 mg l-1 of FeSO4
      x 7H2O), Zn3+ (15 mg l-1 of ZnSO4 x 7H2O), Cu2+ (0.5 mg l-1 of CuSO4 x 5H2O) and
      thiamine-HCL (1 mg l-1). Galacto-oligosaccharide production was maintained at
      high levels during six cycles of production, with the amount of Gal-OS produced
      in each cycle being more than 216 mg ml-1 (weight yield of more than 60%.

PMID- 9569698
TI  - Detection of Yersinia enterocolitica in food by PCR amplification.
AB  - A polymerase chain reaction (PCR) assay was developed for detection of
      pathogenic, virulent strains of Yersinia enterocolitica. By using both virulence
      loci virF and ail as markers for pathogenicity, detection of species with a
      virulence factor present was possible. DNA preparation in the presence of
      hexadecyl trimethy ammonium bromide (CTAB) was followed by two 44 cycle
      amplification reactions, one for each of the markers. As few as 10(2) Y.
      enterocolitica cells were detected in ground pork in the presence of 10(5)-10(6)
      bacteria of other species. The described PCR assay provides a sensitive robust
      assay for the detection of virulent Y. enterocolitica in food.

PMID- 9569699
TI  - A blood-free enrichment medium for growing Campylobacter spp. under aerobic
      conditions.
AB  - Detection limits for Campylobacter jejuni strains JH93 and ATCC 29428 in a new
      blood-free enrichment broth (BFEB) were investigated under aerobic conditions.
      Cultures of Camp. jejuni were inoculated into 50 ml BFEB containing 10% food
      homogenate in 50 ml screw-cap tubes. After 24 h enrichment under aerobic
      conditions, Camp. jejuni were isolated on four selective agar media. The least
      squares means of the detection limit 50% endpoint (DL50) values were 0.4 (plain
      BFEB), 0.9 (crabmeat), 1.7 (mushroom), 1.7 (raw milk) and 2.1 (oyster) colony
      forming units (cfu) 5 g-1 food. The efficiency of the BFEB was significantly
      affected (P < 0.05) by food type and bacterial strain. Overall, the BFEB
      enrichment compared favourably with the existing US Food and Drug Administration
      method under modified atmosphere. In addition, the BFEB method did not require
      the use of blood, special equipment or Oxyrase to reduce oxygen tensions.

PMID- 9569700
TI  - Possible link between a 35 kDa membrane protein and osmolyte transport in
      Staphylococcus aureus.
AB  - Accumulation of proline and glycine betaine occurs via three transport systems in
      Staphylococcus aureus (Pourkomailian and Booth 1992, 1994). A 35 kDa membrane
      protein was identified to be missing from a mutant, BP108, which lacks activity
      of the low affinity osmolyte transport system. The loss in activity of the low
      affinity transport system may be linked to the loss in expression of the 35 kDa
      membrane protein as a result of transposon insertion.

PMID- 9569701
TI  - Vancomycin susceptibility as an aid to the identification of lactobacilli.
AB  - Forty strains of lactobacilli isolated from probiotic supplements or functional
      foods, and two clinical isolates, have been identified by API 50 CHL and tested
      for susceptibility to vancomycin. All the Lactobacillus acidophilus (16) and
      Lact. delbreuckii (two) strains were sensitive to vancomycin, while all the other
      strains (mainly Lact. rhamnosus, 15) were resistant. Susceptibility to other
      antibiotics was not species-specific. Differential susceptibility to vancomycin
      may be helpful in speciation of lactobacilli.

PMID- 9569702
TI  - Diarrhoeal enterotoxin production by psychrotrophic Baccillus cereus present in
      reconstituted milk-based infant formulae (MIF).
AB  - One hundred reconstituted milk-based infant formulae (MIF) representative of 10
      leading brands available in many European Economic Community countries were
      examined for psychrotrophic Bacillus cereus and for the presence of diarrhoeal
      enterotoxin. Of the 38 B. cereus isolates recovered from MIF, one, four and 16
      strains grew at 4, 6 and 8 degrees C after 15 d. One (2.6%), two (5.3%) and six
      (15.8%) of the isolates were identified as potential psychrotrophic food
      poisoning strains as they were both enterotoxigenic and exhibited good growth at
      4, 6 and 8 degrees C, respectively. Enterotoxin was not detected in MIF in which
      less than 5.36 log10 cfu of B. cereus ml-1 had grown. While psychrotrophic
      enterotoxigenic B. cereus strains occur occasionally in MIF, brief storage of
      reconstituted MIF at the recommended refrigeration temperature of 4 degrees C
      will allow this product to remain safe for consumption.

PMID- 9569703
TI  - Effect of high-temperature, short-time (HTST) pasteurization on milk containing
      low numbers of Mycobacterium paratuberculosis.
AB  - The efficacy of high-temperature, short-time (HTST) pasteurization (72 degrees
      C/15 s) when low numbers (< or = 10(3) cfu ml-1) of Mycobacterium
      paratuberculosis are present in milk was investigated. Raw cows' milk spiked with
      Myco. paratuberculosis (10(3) cfu ml-1, 10(2) cfu ml-1, 10 cfu ml-1, and 10 cfu
      50 ml-1) was subjected to HTST pasteurization using laboratory pasteurizing
      units. Ten bovine strains of Myco. paratuberculosis were tested in triplicate.
      Culture in BACTEC Middlebrook 12B radiometric medium detected acid-fast survivors
      in 14.8% and 10% of HTST-pasteurized milk samples at the 10(3) and 10(2) cfu ml-1
      inoculum levels, respectively, whereas conventional culture on Herrold's egg yolk
      medium containing mycobactin J detected acid-fast survivors in only 3.7% and 6.7%
      of the same milk samples. IS900-based PCR confirmed that these acid-fast
      survivors were Myco. paratuberculosis. No viable Myco. paratuberculosis were
      isolated from HTST-pasteurized milk initially containing either 10 cfu ml-1 or 10
      cfu 50 ml-1.

PMID- 9569704
TI  - The influence of yeast on thermophilic composting of food waste.
AB  - The microbial changes during thermophilic composting of food waste were
      investigated at 50 degrees C using a laboratory-scale composter. The results
      showed that an early increase in the growth of yeast was followed by the growth
      of thermophilic bacteria, and that subsequently, the yeast declined rapidly. The
      growth interactions of selected strains of yeast and bacteria were studied in
      culture media containing organic acids. The results demonstrated that the acidity
      of the media was reduced during the growth of the yeast. Therefore, it is
      concluded that in the early stages of composting, the growth thermophilic
      bacteria is inhibited by organic acids, and that the growth of yeast enables
      subsequent bacterial growth by removing organic acids from food waste.

PMID- 9569705
TI  - Subtyping of Campylobacter jejuni Penner serotypes 9, 38 and 63 from human
      infections, animals and water by pulsed field gel electrophoresis and flagellin
      gene analysis.
AB  - Pulsed field gel electrophoresis and PCR-RFLP flagellin gene profiling were used
      to discriminate 44 isolates of Campylobacter jejuni Penner heat stable (HS)
      serotypes 9, 38 and 63 from sporadic human infections and other sources. Genomic
      similarities between HS9 and HS38 strains were demonstrated. HS63 and HS1 strains
      of Camp. jejuni ssp. jejuni were similar but were genomically distinct from Camp.
      jejuni ssp. doylei HS63. The molecular analyses provided a basis for assessing
      associations between cross-agglutinating strains of Camp. jejuni and for
      subtyping within those serogroups.

PMID- 9569706
TI  - Typing of Bacillus sporothermodurans and other Bacillus species isolated from
      milk by repetitive element sequence based PCR.
AB  - When analysing raw milk for the presence of Bacillus sporothermodurans, 11
      Bacillus strains were isolated which could be differentiated from known Bacillus,
      Brevibacillus and Paenibacillus spp. by different primer specificity in PCR
      experiments, indicating that they probably belong to Bacillus species as yet
      undescribed. Using repetitive element sequence based PCR (REP-PCR), these 11
      strains could be clearly distinguished from B. sporothermodurans as well as from
      each other. Eighty-five B. sporothermodurans strains were characterized by a
      typical REP-pattern. Using REP-PCR combined with separation on non-denaturing
      polyacrylamide gel electrophoresis and silver staining, individual B.
      sporothermodurans strains could be discriminated, which was not possible by
      methods previously published.

PMID- 9569707
TI  - Genetic diversity of Ornithobacterium rhinotracheale strains isolated from
      poultry in France.
AB  - Twenty-three strains of Ornithobacterium rhinotracheale from various origins,
      associated with respiratory pathology of birds, were compared using plasmid
      profiles, ribotyping and Random Amplified Polymorphic DNA (RAPD) in order to
      achieve a precise strain characterization as well as to highlight the
      relationships between these strains. No plasmid could be detected. These strains
      were poorly discriminated by ribotyping although different enzymes were used. The
      RAPD analysis has given reproducible DNA fingerprints and a good level of
      discrimination. This method can be used with only one or two primers to
      differentiate the O. rhinotracheale strains and could be used in epidemiological
      studies.

PMID- 9569709
TI  - Dynabeads plus 3 M Petrifilm HEC versus Vitek Immunodiagnostic Assay System for
      detection of E. coli O157 in minced meat.
AB  - The potentially low infective dose of Escherichia coli O157 makes it necessary to
      be able to detect low numbers in food, and the lack of sensitivity of direct
      plating has led to the development of various enrichment and detection methods.
      Until now, the most selective procedure for detection of E. coli O157 isolates
      was the immunomagnetic separation (IMS) method. The number of sorbitol non
      fermenting micro-organisms other than E. coli O157 that adhere non-specifically
      to the magnetic beads hampers the application of IMS. The use of IMS in
      conjunction with 3 M Petrifilm-HEC yielded EHEC O157 in 21 of 165 samples of
      minced meat (12.7%). Without advance application of IMS, Petrifilm plates often
      yield confluent growth and colonies too numerous to count. The Vitek
      Immunodiagnostic Assay System (VIDAS-ECO) showed good sensitivity when testing
      artificially contaminated beef samples, but only four of 21 naturally
      contaminated samples were recognized. The addition of 3 M Petrifilm to IMS
      resulted in less growth of contaminants and eliminated much of the need to test
      presumed colonies for confirmation. The combination of IMS and 3 M Petrifilm-HEC
      is a fast and efficient screening procedure for E. coli O157 in minced meat.

PMID- 9569708
TI  - Effects of tea tree oil on Escherichia coli.
AB  - Tea tree oil (TTO) stimulates autolysis in exponential and stationary phase cells
      of Escherichia coli. Electron micrographs of cells grown in the presence of TTO
      showed the loss of electron dense material, coagulation of cell cytoplasm and
      formation of extracellular blebs. Stationary phase cells demonstrated less TTO
      stimulated autolysis and also had greater tolerance to TTO-induced cell death,
      compared to exponentially grown cells. It was also revealed that subpopulation of
      stationary phase cells demonstrated increased tolerance to TTO-bactericidal
      effects.

PMID- 9569710
TI  - Incidence of Listeria spp. in Breton live shellfish.
AB  - Live shellfish samples (120) were collected from nine littoral sites in Brittany
      (western France). They were screened for Listeria spp. and a count of faecal
      coliforms was carried out. Analysis of the results revealed Listeria spp. in 55%
      of samples, a much higher rate than the previous, infrequent, recorded data.
      Furthermore, the study demonstrated that the frequency of Listeria spp. in winter
      was more important than in summer (P < 0.001), and underlined a significant
      relationship between the occurrence of these bacteria and the concentration of
      faecal coliforms (P < 0.001). Finally, comparison of the official and Gen-Probe
      methods revealed the limits of the standardized technique in the search for L.
      monocytogenes in shellfish.

PMID- 9569711
TI  - The synergistic preservative effects of the essential oils of sweet basil (Ocimum
      basilicum L.) against acid-tolerant food microflora.
AB  - Essential oils extracted by hydrodistillation from five different varieties of
      Ocimum basilicum L. plants (Anise, Bush, Cinnamon, Dark Opal and a commercial
      sample of dried basil) were examined for antimicrobial activity against a wide
      range of foodborne Gram-positive and -negative bacteria, yeasts and moulds by an
      agar well diffusion method. All five essential oils of basil showed antimicrobial
      activity against most of the organisms tested with the exception of Flavimonas
      oryzihabitans and Pseudomonas species. The inhibitory effect of Anise oil, in
      comparison with mixtures of the predominant components of pure linalool and
      methyl chavicol, against the acid-tolerant organisms, Lactobacillus curvatus and
      Saccharomyces cerevisiae, was examined in broth by an indirect impedance method.
      Synergistic effects between Anise oil, low pH (pH 4.2) and salt (5% NaCl) were
      determined. The antimicrobial effect of Anise oil was also assessed in a tomato
      juice medium by direct viable count, showing that the growth of Lact. curvatus
      and S. cerevisiae was completely inhibited by 0.1% and 1% Anise oil,
      respectively. The results of the current study indicate the need for further
      investigations to understand the antimicrobial effects of basil oils in the
      presence of other food ingredients and preservation parameters.

PMID- 9569712
TI  - Inhibition effect of enterocin CCM 4231 in the rumen fluid environment.
AB  - Enterocin CCM 4231 is a bacteriocin with a broad antimicrobial spectrum produced
      by the ruminal strain Enterococcus faecium CCM 4231. Its inhibitory effect
      towards enterococci, Ent. faecium EF 26/42, staphylococci, Streptococcus bovis AO
      24/85 and Escherichia coli, as well as towards Listeria monocytogenes OHIO
      strain, in the rumen fluid environment was studied during culture at 37 and 30
      degrees C for 24 h and 20 days. Enterocin CCM 4231 was added to the samples at a
      concentration of 3200 AU ml-1. The best inhibitory effect was noted against
      enterococci at both cultivation temperatures. A decrease in total cell count from
      10(8) cfu ml-1/or 10(4) cfu ml-1 and from 10(5) cfu ml-1 to 10(1) cfu ml-1 was
      detected. Addition of enterocin to the rumen fluid also inhibited staphylococci
      (from 10(5) cfu ml-1 to 10(4) cfu ml-1 and/or 10(3) cfu ml-1). Gram-negative E.
      coli cells were inhibited at both cultivation temperatures (decrease from 10(6)
      cfu ml-1 to 10(1) cfu ml-1 at 37 degrees C, and from 10(7) cfu ml-1 to 10(5) cfu
      ml-1 at 30 degrees C). Enterococcus faecium EF 26/42 and Streptococcus bovis AO
      24/85, the strains growing in the rumen fluid, were the most sensitive to the
      addition of enterocin during the first 24 h of fermentation (decrease from 10(10)
      cfu ml-1 and 10(8) cfu ml-1 to 10(6) cfu ml-1 and 10(4) cfu ml-1). An
      antilisterial effect of the bacteriocin was also confirmed. Further application
      of bacteriocin in ruminal ecology was indicated.

PMID- 9569713
TI  - Prominent occurrence of ribosomes from an uncultured bacterium of the
      Verrucomicrobiales cluster in grassland soils.
AB  - An uncultured bacterium of the Verrucomicrobiales cluster was identified by its
      16S rDNA sequence as a major bacterium in Dutch Drentse A grassland soils.
      Potential metabolic activity of the according organism was estimated by applying
      direct ribosome isolation from soil and partial amplification of the 16S rRNA via
      RT-PCR using bacteria-specific primers. Temperature gradient gel electrophoresis
      separated the amplicons sequence specifically into reproducible fingerprints. One
      of the fingerprint bands matched with the signal of clone DA101. Southern blot
      hybridization with a DA101-specific V6 probe confirmed sequence identity. It is
      the first time that an organism of the Verrucomicrobiales cluster has been
      indicated as a potential major metabolizer in environmental microbial
      communities.

PMID- 9569714
TI  - The content of prostaglandins and their precursors in Mortierella and
      Cunninghamella species.
AB  - Five strains of filamentous fungi belonging to the genera Mortierella and
      Cunninghamella were examined for the content of dihomo-gamma-linolenic,
      arachidonic, eicosapentaenoic acids and prostaglandins (type E2 and F2 alpha).
      Prostaglandins were detected using an ELISA method in mycelia of all tested
      strains (range 50-4800 ng g-1 of PGE2 and 6-30 ng g-1 of PGF2 alpha). Several
      micro-organisms also produced prostaglandins in the culture medium (2.2-137.6
      micrograms 1-1 for PGE2 and 0.4-7.8 micrograms 1-1 for PGF2 alpha).

PMID- 9569715
TI  - Effects of high hydrostatic pressure on Clostridium sporogenes spores.
AB  - Spores of Clostridium sporogenes were found to be resistant to ultra high
      pressure, with treatments of 600 MPa for 30 min at 20 degrees C causing no
      significant inactivation. Combination treatments including heat and pressure
      applied simultaneously (e.g. 400 MPa at 60 degrees C for 30 min) or sequentially
      (e.g. 80 degrees C for 10 min followed by 400 MPa for 30 min) proved more
      effective at inactivating spores. Pressure cycling (e.g. 60 MPa followed by 400
      MPa at 60 degrees C) also reduced spore numbers. Overall, these pressure
      treatments resulted in less than a 3 log reduction, and it was concluded that the
      spores could not be inactivated by pressure alone. This could indicate that for
      the effective inactivation of bacterial spores, high pressure technology may have
      to be used in combination with other preservation methods.

PMID- 9569716
TI  - Plantaricin D, a bacteriocin produced by Lactobacillus plantarum BFE 905 ready-to
      eat salad.
AB  - Lactobacillus plantarum BFE 905 isolated from 'Waldorf' salad produced a
      bacteriocin termed plantaricin D which was active against Lact. sake and Listeria
      monocytogenes strains. Plantaricin D was heat stable, retaining activity after
      heating at 121 degrees C. The bacteriocin was inactivated by alpha-chymotrypsin,
      trypsin, pepsin and proteinase K, but not by papain and other non-proteolytic
      enzymes tested. Plantaricin D was stable at pH values ranging from 2.0 to 10.0.
      The bacteriocin inhibited growth of L. monocytogenes in automated turbidity
      assays. Although Lact. Plantarum BFE 905 harboured plasmids ranging in size from
      3 to 55 kilobase pairs, loss of bacteriocin production could not be correlated
      with plasmid loss. A role for bacteriocin-producing Lact. plantarum of vegetable
      origin in assuring the safety of vegetable foods is suggested.

PMID- 9569717
TI  - Educational programs for deaf students.

PMID- 9569718
TI  - Thirty years of the Annual Survey of Deaf and Hard-of-Hearing Children & Youth: a
      glance over the decades.

PMID- 9569719
TI  - University and college programs for personnel in deafness.

PMID- 9569721
TI  - Program and services for the deaf. Supportive and rehabilitative programs.

PMID- 9569720
TI  - Programs for deaf-blind children and adults.

PMID- 9569722
TI  - [73rd annual meeting of the Japanese Society for Tuberculosis. Niigata City,
      Japan. April 16-17, 1998. Abstracts].

PMID- 9569723
TI  - [The 71st general meeting of Japanese Leprosy Association. Okinawa, Japan. June 3
      5, 1998. Abstracts].

PMID- 9569724
TI  - [The 95th meeting of the Japanese Society of Internal Medicine. Fukuoka, Japan.
      April 9-11, 1998. Abstracts].

PMID- 9569725
TI  - [The 71st annual meeting of the Japanese Society for Bacteriology. Nagano, Japan.
      April 2-4, 1998. Abstracts].

PMID- 9569726
TI  - [Changes of paradigms in psychiatry].
AB  - During the last centuries mental illnesses represented brain disorder. About
      hundred years ago--instead of gradually accumulating neurophysiological knowledge
      -the focus of attention shifted to investigation of abnormal mental states
      divorced from cerebral function. The advance of the brain research and
      psychopharmacology has been progressively narrowing the marked demarcation
      between organic and functional (psychogenic) syndromes. Till the end of the
      seventies the psychotic patients were treated in closed mental wards, the
      neurotics in open neurological ones in the common departments for neurology and
      psychiatry. The modernization of the mental care system started when psychiatry
      became independent of the neurology. The psychotherapy-despite of the
      international acknowledgement of the Hungarian psychoanalysts-has developed only
      in the last third of this century. The opposition of the biological and
      psychodynamic approaches theoretically refer to the presumed physical or mental
      origin, whereas mental function means the summation of variety of electrical and
      chemical events occurring in the brain. The asylums have gradually progressed to
      the open wards and therapeutic communities. Beside of the hospital treatment the
      outpatient care became a matter of primary importance, but the system of out-of
      hospital alternatives, day-hospitals, halfway institutes, patient's homes, work
      places have been lacking. The modern psychiatric care system is moving forward
      the community in spite of its resistance. The psychiatric patients suffer not
      only from their mental symptoms and experienced disability, but mainly from the
      unfavorable attitudes of the immediate and social environment. The biological,
      psychological and sociological factors determine the origin, the treatment and
      the outcome of the mental disorders; neither of them can neglect without
      disadvantage of the other two.

PMID- 9569727
TI  - [Successful treatment of hepatocellular carcinoma with All-trans-retinoic acid].
AB  - A 44-year-old female patient was admitted to our department with diagnosis of
      malignant lymphoma. The abdominal USG and CT showed multiple liver lesions with
      partial portal vein thrombosis, moderately increased alfa-fetoprotein (AFP),
      ASAT, ALAT (2x normal value), serology was negative for HBV and HCV. Liver
      transplantation was suggested but refused because of portal vein thrombosis. ATRA
      (45 mg/m2/day orally) was given on the basis of the assumption that HCC and acute
      promyelocytic leukaemia share similar oncogenic pathway (alter the RAR alpha and
      beta receptors). She was gained 15 kg-s and has resumed her work as a teacher for
      the last 20 months. Abdominal CT showed a complete regression of the intrahepatic
      tumour.

PMID- 9569728
TI  - [Prevention of thromboembolic side effects of oral contraceptives: methodologic
      recommendations].
AB  - The authors analyse the incidence of thromboembolic complications during combined
      oral contraception. Among genetic factors predisposing to venous thrombosis and
      thromboembolic disease, they present, with the help of three case histories, the
      molecular biology of activated protein-C resistance, the newly discovered and
      most frequently implicated pathogenetic factor of inherited thrombophilia. Among
      350 asymptomatic women requesting prescription for an oral contraceptive they
      found a 9.1% frequency of heterozygote Leiden-mutation carriers. For the
      prevention of a rare, however, almost always life-threatening complication the
      authors recommend activated protein C-resistance analysis to be carried out
      whenever an oral contraceptive is prescribed for the first time. Positive results
      will provide life-time aid in avoiding factors which increase the risk of
      thromboembolic disease. Negative results may help reducing the number of those
      who, risking an unwanted pregnancy, are hesitant to start on oral contraceptives
      for their implication in thromboembolic disease.

PMID- 9569729
TI  - [Cytokines in rheumatoid arthritis: new therapeutic possibilities].
AB  - The ingress of inflammatory leukocytes into the synovium is important for the
      pathogenesis of rheumatoid arthritis. Soluble inflammatory mediators regulate the
      inflammatory, chemotactic, adhesive, angiogenic events, as well as osteopenia
      associated with this disease. In this review authors discuss the role of a number
      of inflammatory mediators, such as cytokines, chemokines and growth factors in
      these processes. The outcome of arthritis is highly dependent on the imbalance
      between pro-inflammatory and anti-inflammatory mediators. Cytokine-related
      research also has important clinical relevance. Many of these proteins are
      detectable in the serum of rheumatoid patients and may eventually serve as useful
      laboratory markers of disease activity. Antirheumatic therapy currently used for
      the treatment of rheumatoid arthritis is often limited. Therefore, we need to
      consider alternative therapeutic regimens, such as the inhibition of cytokines
      and other soluble mediators, in order to prevent severe joint destruction. While
      there are many complex interactions involving cytokine networks and cascades in
      the arthritic joint, there are promising attempts to eliminate a single cytokine
      in clinical trials, such as ablation of tumor necrosis factor-alpha. Hopefully,
      the study of cytokines and their networks will lead to specific immunomodulatory
      therapies that will benefit rheumatoid patients by preventing joint destruction.

PMID- 9569730
TI  - [Vulvar melanosis and vitiligo].
AB  - Clinically it is impossible to make difference between the vulvar melanosis the
      harmless brown spotty change of the vulva and melanoma malignum, that is one of
      the most dangerous malignancies. Even the dermatoscopical examination was not
      efficient to exclude the melanoma surely. A small, representative biopsy was
      enough for the diagnosis, which has exempted the patient from the unjustified
      mutilating resections. On the patient's skin they detected also a few relatively
      small disseminated hypopigmented spots. Electronmicroscopically they could
      observe plenty of melanosomes and big melanosoma-complexes in the lower
      keratinocyte layers of the vulvar melanotic macules. Melanocytes could not be
      recognised in the hypopigmented spots.

PMID- 9569731
TI  - [Message from Endre Hogyes to posterity].

PMID- 9569732
TI  - [Diseases and death of Handel].

PMID- 9569733
TI  - [NCCLS/JCCLS guideline for urinalysis--the process of the establishment and
      summary of the guideline].

PMID- 9569734
TI  - [Pathophysiology of the kidney and urinalysis].

PMID- 9569735
TI  - [Pathophysiology of the urinary system and urinalysis].

PMID- 9569736
TI  - [Qualitative analysis of the urine--problems, their management, quality control,
      systematization, and the future prospect].

PMID- 9569737
TI  - [Urinary proteins. a. Quantitative analysis and its standardization].

PMID- 9569739
TI  - [Urinary proteins. c. Protein fractions].

PMID- 9569738
TI  - [Urinary proteins. b. Microalbuminuria and low molecular weight proteins in the
      urine].

PMID- 9569740
TI  - [Urinary proteins. d. Relationship with diseases].

PMID- 9569741
TI  - [Clinical significance of the urinary sedimentation test].

PMID- 9569742
TI  - [Examination of urinary sediments: clinical examples].

PMID- 9569743
TI  - [Tests for urinary sediments: clinical examples. a. Examination of urinary
      erythrocytes and leukocytes].

PMID- 9569745
TI  - [Tests for urinary sediments: clinical examples. c. Urinary casts].

PMID- 9569746
TI  - [Tests for urinary sediments: clinical examples. d. Morphology of urinary
      erythrocytes].

PMID- 9569744
TI  - [Tests for urinary sediments: clinical examples. b. Atypical cells].

PMID- 9569747
TI  - [Efficacy and problems associated with automatic analyzers of urinary sediments].

PMID- 9569749
TI  - [Efficacy and problems associated with automatic analyzers of urinary sediments.
      b. Evaluation of Hitachi 6700].

PMID- 9569748
TI  - [Efficacy and problems associated with automatic analyzers of urinary sediments.
      a. Introduction of UF-100 to daily operations].

PMID- 9569750
TI  - [Addictive drugs and doping tests].

PMID- 9569751
TI  - [Parasitic diseases and laboratory tests. a. Protozoans].

PMID- 9569753
TI  - [Digestive system diseases and fecal occult blood].

PMID- 9569752
TI  - [Parasitic diseases and diagnostic tests. b. Parasitic (helminth) infections of
      current interest--trends and management].

PMID- 9569754
TI  - [Biochemical tests of the cerebrospinal fluid and body fluids obtained by
      puncturing].

PMID- 9569755
TI  - [Cytological examinations].

PMID- 9569756
TI  - Optical time-of-flight chemical detection: spatially resolved analyte mapping
      with extended-length continuous chemically modified optical fibers.
AB  - We theoretically evaluate and experimentally verify a novel strategy for
      spatially resolved analyte mapping over extended remote areas. The approach
      combines a method for the fabrication of continuous extended-length sensors with
      optical time-of-flight chemical detection (OTOF-CD). The use of OTOF-CD makes it
      possible to locate the zones in the fiber where attenuation or fluorescence takes
      place, to determine the magnitude of these variations, and to relate the
      magnitude of the variations to the local concentration or concentrations of a
      single analyte or several analytes. Simulation experiments suggest that OTOF-CD
      should provide spatial resolution close to its theoretical limit by deconvolution
      of the returned wave form with all time-dependent experimental variables (laser
      pulse width, reagent fluorescence lifetime, etc.). The signal-processing
      technique should be useful for a wide variety of sensors based on absorption,
      refractive index, or statically and dynamically quenched fluorescence.
      Experimental results with a model system (a 48-m-long oxygen sensor) compare
      favorably with those predicted by numerical simulations. Possible experimental
      difficulties in the realization of these novel sensors are discussed as are ways
      to overcome them.

PMID- 9569757
TI  - Flow injection immunoanalysis based on a magnetoimmunosensor system.
AB  - A new immunosensor integrated to a flow system has been developed. It is based on
      magnetic immunoparticles immobilized on a solid-state transducer using a magnetic
      field. The described technique renews the immunoparticles reproducibly for each
      analysis allowing a good measurement precision. The developed experimental
      approach permits the implementation of an automated immunoassay that is quick
      (analytical cycle < 30 min) and sensitive in the micromolar concentration range.
      The system was applied to the determination of rabbit immunoglobulin G as an
      analyte model.

PMID- 9569758
TI  - Electrochemistry in microscopic domains. 1. The electrochemical cell and its
      voltammetric and amperometric response.
AB  - Microscopic aqueous sample droplets of nano- and picoliter volumes were formed on
      the bottom of a polystyrene dish under water-saturated heptane. The
      electrochemical cell consisted of a beveled carbon fiber microdisk working
      electrode and a reference electrode with a miniature junction, both inserted into
      the studied droplet. Both electrodes had a nominal tip diameter of 7.5 microns.
      Cyclic voltammetry and chronoamperometry in droplets of 3.3 mM ruthenium
      hexaammine trichloride in 0.1 M KCl solution were performed with this system. The
      experiments revealed for the first time major deviations in both voltammetric and
      amperometric microelectrode behavior in picoliter domains as compared to
      nanoliter volume and bulk solution. The concept and criteria of electrochemical
      microscopicity of volume is discussed. This work also provides a simple and
      robust experimental model system to verify electrochemical experiments in
      restricted domains such as in or near single biological cells or in microscopic
      tissue cavities. The methodology developed has, however, more general analytical
      and physicochemical applications as well.

PMID- 9569760
TI  - Construction and characterization of nitrate reductase-based amperometric
      electrode and nitrate assay of fertilizers and drinking water.
AB  - The construction and characterization of a nitrate reductase-based amperometric
      electrode for determination of nitrate ion is described. The electrode consisted
      of nitrate reductase held by dialysis membrane onto a Nafion-coated glassy carbon
      electrode. Methyl viologen was allowed to absorb into the Nafion layer, which
      acted as a reservoir for the electron mediator. The utility of the electrode to
      assay fertilizer and water sample for nitrate was demonstrated. The assays
      conducted with this electrode compared well with colorimetric and potentiometric
      assays of the same samples.

PMID- 9569759
TI  - Influence of nonionic surfactants on the potentiometric response of ion-selective
      polymeric membrane electrodes designed for blood electrolyte measurements.
AB  - The effect of the nonionic surfactants Brij 35 and Triton X-100 on the
      selectivity of neutral carrier-based ion-selective electrodes (ISEs) commonly
      used for measurements of electrolytes in whole blood is investigated. Studies are
      conducted with plasticized PVC membranes doped with several neutral ionophores
      commonly employed to prepare clinically useful potassium, calcium, and sodium
      ISEs. An observed increase in the electrodes' EMF values upon the addition of
      surfactant to the test solution suggests a change in the ion selectivity of the
      polymeric membranes in the presence of Brij 35 or Triton X-100. For membranes
      doped with K(+)-selective valinomycin, the effect of nonionic surfactants is
      relatively small. However, in the case of calcium-selective membranes prepared
      with ETH 1001 and ETH 129, nonionic surfactants, especially Triton X-100,
      decrease the selectivity for calcium over potassium cations by nearly 1 order of
      magnitude. Such behavior is even more dramatic for sodium-selective membranes,
      with the degree of surfactant-induced loss of ion selectivity dependent on the
      specific sodium ionophore employed, the lipophilic tetraphenylborate derivative
      content of the membrane, and the surfactant type. A detailed theoretical model is
      presented to explain the effect of nonionic surfactants on the EMF response
      function of cation-selective polymeric membrane electrodes. Experimental results
      are in good agreement with theoretical predictions based on known binding
      constants for ionophores and surfactants with given cations.

PMID- 9569761
TI  - A sample purification method for rugged and high-performance DNA sequencing by
      capillary electrophoresis using replaceable polymer solutions. A. Development of
      the cleanup protocol.
AB  - A method for the cleanup of Sanger DNA sequencing reaction products for capillary
      electrophoresis analysis with replaceable polymer solutions has been developed. A
      poly(ether sulfone) ultrafiltration membrane pretreated with linear
      polyacrylamide was first used to remove template DNA from the sequencing samples.
      Then, gel filtration in a spin column format (two columns per sample) was
      employed to decrease the concentration of salts below 10 microM in the sample
      solution. The method was very reproducible and increased the injected amount of
      the sequencing fragments 10-50-fold compared to traditional cleanup protocols.
      Using M13mp18 as template, the resulting cleaned-up single DNA sequencing
      fragments could routinely be separated to more than 1000 bases with a base
      calling accuracy of at least 99% for 800 bases. The method is simple and
      universal and can be easily automated. In the following paper, a systematic study
      to determine quantitatively the effects of the sample solution components such as
      high-mobility ions (e.g., chloride and dideoxynucleotides) and template DNA on
      the injected amount and separation efficiency of the sequencing fragments is
      presented.

PMID- 9569762
TI  - A sample purification method for rugged and high-performance DNA sequencing by
      capillary electrophoresis using replaceable polymer solutions. B. Quantitative
      determination of the role of sample matrix components on sequencing analysis.
AB  - In the previous paper, a sample cleanup procedure for DNA sequencing reaction
      products was developed, in which template DNA was removed by ultrafiltration and
      the total concentration of salts (chloride and di- and deoxynucleotides) was
      decreased below 10 microM using gel filtration. In this paper, a quantitative
      study of the effects of these sample solution components on the injected amount
      and separation efficiency of the sequencing fragments in capillary
      electrophoresis is presented. The presence of chloride and deoxynucleotides in a
      total concentration above 10 microM in the sample solution significantly
      decreased the amount of DNA sequencing fragments injected into the capillary
      column. However, the separation efficiency was not affected upon increasing the
      amount of salt. On the other hand, in the presence of only 0.1 microgram of
      template in the sample (one-third of the lowest quantity recommended in cycle
      sequencing) and at very low chloride concentration (approximately 5 microM), the
      separation efficiency decreased by 70%, and the injected amount of DNA sequencing
      fragments was 40% lower compared to the sample cleaned by the new purification
      method. The deleterious effect of template DNA on the separation of sequencing
      fragments was suppressed in the presence of salt in a concentration above 100
      microM in the sample solution. Separately, it was found that both the electric
      field strength and duration of injection affected the resolution of DNA
      sequencing fragments when the cleaned up sample solution was used. Separation
      efficiencies of 15 x 10(6) theoretical plates/m were achieved when the sample was
      loaded at low electric field, e.g., 25 V/cm for 80 s or less. The results
      demonstrate that the sample solution components (chloride, deoxynucleotides,
      template DNA) and injection conditions must be controlled to achieve high
      performance and rugged DNA sequencing analysis.

PMID- 9569763
TI  - MALDI mass spectrometry of dye-peptide and dye-protein complexes.
AB  - Immobilized sulfonate dyes are widely used for protein separation and
      purification, but the mode of interaction between the dye molecules and the
      proteins is largely unknown. Here we show that specific noncovalent dye-protein
      and dye-peptide complexes can be observed using MALDI mass spectrometry. We prove
      that the interaction is prodominantly electrostatic and that it involves
      protonated sites of the peptides and proteins, including the NH2 terminus, and
      deprotonated SO3 groups of the dyes. Furthermore, we show that MALDI-MS of such
      complexes with a nonacidic matrix, p-nitro-aniline, can be used to determine the
      number of accessible basic sites of a protein or peptide in its folded structure.
      Our results are in good agreement with measurements of the same property done
      with electrospray ionization.

PMID- 9569764
TI  - Derivatization for electrospray ionization mass spectrometry. 3.
      Electrochemically ionizable derivatives.
AB  - In this paper, the use of ferrocene-based "electrochemically ionizable"
      derivatives to enhance ES-MS analysis of simple alcohols, sterols, and phenols is
      discussed. These derivatives are designed to take advantage of the electrolysis
      process inherent to operation of the ES ion source for selective ionization.
      Derivatization procedures, electrochemical character of the derivatives, and the
      ES-MS operational parameters necessary to maximize electrochemical ionization and
      to enhance gas-phase detection are presented with reference to ferrocenecarbamate
      ester derivatives of a variety of alcohol standards, as well as the
      ferroceneboronate derivative of the diol, pinacol. Tandem mass spectrometric
      analysis of the derivatives (precursor and product ion spectra) is shown to
      provide derivative confirmation, enhanced detection, and additional analyte
      structure information. The utility of this derivatization approach for the
      selective detection of alcohols in complicated mixtures is demonstrated using a
      saw palmetto (Serenoa repens) fruit extract known to contain a variety of
      alcohols at low levels.

PMID- 9569765
TI  - Direct mass spectrometric analysis of in situ thermally hydrolyzed and methylated
      lipids from whole bacterial cells.
AB  - Fatty acid methyl esters (FAMEs) were generated in situ, during pyrolysis, from
      whole-cell bacterial samples and analyzed by mass spectrometry (MS). The FAME
      profiles obtained by an in situ thermal hydrolysis methylation (THM) step were
      compared with gas chromatography (GC) and MS analyses of the chemically extracted
      and methylated fatty acids. This correlation was based on the ability of each
      technique to differentiate a representative group of 15 bacteria at the species
      level as predicted by principal component analysis. All three analyses, GC/FAME,
      pyrolysis-MS/FAME, and in situ THM-MS/FAME differentiated the studied bacterial
      sample set into three discrete clusters. The bacteria comprising each cluster
      were the same for all three analyses, showing that taxonomic information of the
      lipid profiles was preserved in the Py-MS/FAME and in situ THM-MS/FAME analyses
      of whole cells. Contributions from saturated, unsaturated, cyclopropyl, and
      branched bacterial fatty acids to the differentiation of microorganisms were
      identified for all three analyses. The in situ THM-MS/FAME approach is simple,
      requires small samples (approximately 2 x 10(6) cells/profile), and is rapid,
      with a total analysis time under 5 min/sample.

PMID- 9569766
TI  - MALDI mass spectrometry combined with avidin-biotin chemistry for analysis of
      protein modifications.
AB  - A general mass spectrometric method that combines purification and analysis in
      one step is described for the rapid and sensitive determination of protein
      modification that involves covalent attachment of a modifying group. In this
      method, the modifying group is first labeled with a biotin moiety, and the
      covalent interaction of this group with the targeted protein results in a
      biotinylated product. The modified protein can then be subjected to enzymatic
      digestion, followed by the isolation of the biotinylated peptide based on a
      previously described MALDI method incorporating the avidin-biotin interaction
      (Schriemer, D. C.; Li, L. Anal. Chem. 1996, 68, 3382-3387). To illustrate the
      validity of the method, a study of a model system was undertaken, involving the
      interaction between avian skeletal muscle troponin C and a sulfhydryl-specific
      biotinylation reagent. It is shown that isolation of a modified peptide with an
      immobilized avidin product could be achieved, even in the presence of an excess
      of contaminating protein. Exoproteases could be added to the crude tryptic digest
      to generate peptide ladders, each containing biotin, which could be analyzed by
      the avidin-biotin/MALDI method for sequence information. Complementary sequence
      information could be obtained from the application of this technique in a tandem
      sector/time-of-flight mass spectrometer for MALDI MS/MS analysis, which allowed
      for the identification of the modification site.

PMID- 9569767
TI  - Measurement of protein charge and ion binding using capillary electrophoresis.
AB  - A new technique is described for the rapid and accurate measurement of
      electrophoretic mobilities of proteins in different solution environments using
      capillary electrophoresis. Data were obtained at different pH using surface
      modified capillaries to reduce nonspecific protein adsorption and using
      hydrodynamic mobilization to improve reproducibility and overall accuracy. The
      net protein charge and extent of anion binding were evaluated from the mobility
      data obtained in different pH and ionic environments for bovine serum albumin.
      The results were in good agreement with titration data obtained using ion
      selective electrodes and mobility data obtained using free solution
      electrophoresis. The method requires extremely small amounts of protein (picogram
      quantities and nanoliter volumes) and is easily automated, making it very
      suitable for protein characterization and for initial screening of possible
      separation techniques.

PMID- 9569768
TI  - Method for determining the solubilities of hydrophobic organics in subcritical
      water.
AB  - A rapid and simple method has been developed to determine the solubility of
      organic compounds in water at temperatures from 25 to 250 degrees C and with
      enough pressure to maintain the liquid state ("subcritical" water). Water is
      heated and then passed through a cell containing excess test solute. The water,
      now saturated with solute, is blended with chloroform, cooled, and collected, and
      the chloroform fraction is analyzed by gas chromatography. Replicate
      determinations have typical reproducibilities, indicated by the relative standard
      deviation, of < 5%. Solubilities at 25 degrees C determined by this method are in
      good agreement with published data. Increasing the temperature of water from 25
      degrees C to near the normal melting point of the organic solute results in
      solubility enhancements ranging from 6-fold for naphthalene (at 65 vs 25 degrees
      C) to 130,000-fold for chlorothalonil (at 200 vs 25 degrees C).

PMID- 9569769
TI  - The design of chiral separation media using monodisperse functionalized
      macroporous beads: effects of polymer matrix, tether, and linkage chemistry.
AB  - Porous size monodisperse methacrylate beads containing amino and hydroxyl groups,
      which can be used as a platform for the production of chiral separation media,
      have been prepared using the staged templated suspension polymerization process.
      The monomers 2-hydroxyethyl methacrylate and several tert-butoxycarbonyl
      protected aminoalkyl methacrylates were used for the preparation of both hydroxyl
      and amino-functionalized beads. Attachment of a chiral selector based on L
      valine-3,5-dimethylanilide through a carbamate and a urea linkage, respectively,
      provides chiral stationary phases with excellent enantioselectivities in the
      separation of the enantiomers of 3,5-dinitrobenzamido derivatives of alpha-amino
      acids. For comparison purposes, a separation medium was also prepared by the
      direct polymerization of a chiral monomer analogous to the hydroxyethyl
      methacrylate-based stationary phase. The chiral stationary phases prepared with
      the N-methyl-2-aminoethyl methacrylate platform exhibit the best selectivity, and
      separation factors as high as 15 were achieved under normal-phase HPLC
      conditions.

PMID- 9569772
TI  - Heterochrony and allometry: the analysis of evolutionary change in ontogeny.
AB  - The connection between development and evolution has become the focus of an
      increasing amount of research in recent years, and heterochrony has long been a
      key concept in this relation. Heterochrony is defined as evolutionary change in
      rates and timing of developmental processes; the dimension of time is therefore
      an essential part in studies of heterochrony. Over the past two decades,
      evolutionary biologists have used several methodological frameworks to analyse
      heterochrony, which differ substantially in the way they characterize
      evolutionary changes in ontogenies and in the resulting classification, although
      they mostly use the same terms. This review examines how these methods compare
      ancestral and descendant ontogenies, emphasizing their differences and the
      potential for contradictory results from analyses using different frameworks. One
      of the two principal methods uses a clock as a graphical display for comparisons
      of size, shape and age at a particular ontogenic stage, whereas the other
      characterizes a developmental process by its time of onset, rate, and time of
      cessation. The literature on human heterochrony provides particularly clear
      examples of how these differences produce apparent contradictions when applied to
      the same problem. Developmental biologists recently have extended the concept of
      heterochrony to the earliest stages of development and have applied it at the
      cellular and molecular scale. This extension brought considerations of
      developmental mechanisms and genetics into the study of heterochrony, which
      previously was based primarily on phenomenological characterizations of
      morphological change in ontogeny. Allometry is the pattern of covariation among
      several morphological traits or between measures of size and shape; unlike
      heterochrony, allometry does not deal with time explicitly. Two main approaches
      to the study of allometry are distinguished, which differ in the way they
      characterize organismal form. One approach defines shape as proportions among
      measurements, based on considerations of geometric similarity, whereas the other
      focuses on the covariation among measurements in ontogeny and evolution. Both are
      related conceptually and through the use of similar algebra. In addition, there
      are close connections between heterochrony and changes in allometric growth
      trajectories, although there is no one-to-one correspondence. These relationships
      and outline links between different analytical frameworks are discussed.

PMID- 9569770
TI  - Near-ultraviolet evanescent-wave absorption sensor based on a multimode optical
      fiber.
AB  - Fiber-optic near-ultraviolet evanescent-wave sensors have been constructed, and
      their feasibility for practical applications has been demonstrated. The sensors,
      used for the detection of ozone near the 254-nm peak of the Hartley absorption
      band, were fabricated from coiled segments of low-cost multimode plastic-clad
      silica optical fibers. The sensing sections were produced alternatively by
      stripping only the protective jacket from the fiber to expose the gas-permeable
      silicone cladding or by stripping the jacket and the cladding to expose the bare
      silica fiber core. Response characteristics are given, including sensitivity to
      ozone, reversibility, and aging effects. The useful lifetime was unacceptably
      short for the sensor that employed the bare-silica core, whereas the exposed
      cladding sensor demonstrated good stability over the entire two-month period of
      investigation. The latter, more useful sensor demonstrated a linear response to
      ozone over the range 0.02-0.35 vol% and a reversible response with a time
      constant on the order of 1 min. Differences in ozone absorption spectra obtained
      in the transmission and evanescent-wave modes are discussed. Projected
      applications of the new exposed-cladding sensor include ozone determination in
      water-treatment processes and ozone production plants.

PMID- 9569773
TI  - Married women's economic dependency in The Netherlands, 1979-1991.
AB  - The present paper offers a replication of an analysis by Sorensen and McLanahan
      (1987) of 1940-1980 USA data on trends in married women's economic dependency,
      this time using Dutch income data for 1979-1991. The results show that in the
      Netherlands, as opposed to the USA, a vast majority of the wives are still
      completely or strongly dependent on their husband's income. Yet, also Dutch
      wives' economic dependency is decreasing at a significant rate. Despite clear
      life course differences that yet seem to persist, we observe declining levels of
      dependency within each age group. This declining trend seems to reflect mostly
      changes in married women's employment status over time. An implication of the
      reported trend, however, is that it becomes increasingly important to study the
      influence of the social position of both partners.

PMID- 9569774
TI  - Explaining women's employment patterns: 'orientations to work' revisited.
AB  - Explanations of the persisting differences in the structure of men's and women's
      employment have long been debated in the social sciences. Sociological
      explanations have tended to stress the continuing significance of structural
      constraints on women's employment opportunities, which persist despite the
      removal of formal barriers. Neo-classical economists, in contrast, have
      emphasized the significance of individual choice, an argument which has been
      recently endorsed by Hakim who suggests that patterns of occupational segregation
      reflect the outcome of the choices made by different 'types' of women. In this
      paper, a previous debate relating to the explanatory utility of men's
      'orientations to work' is used to argue that employment structures are the
      outcome of both choice and constraint, and that this is the case for women, as
      well as men. The argument is illustrated with evidence from cross-nationally
      comparative biographical interviews carried out in five countries.

PMID- 9569775
TI  - Acoustic waves and the real-time study of biochemical macromolecules at the
      liquid/solid interface.
AB  - The adsorption of the proteins, bovine serum albumin, fibrinogen, avidin and
      neutravidin (non-glycosylated form of avidin) to a variety of surfaces imposed on
      thickness shear mode sensors in examined in a flow-injection analysis format. In
      all cases, adsorption of these moieties was essentially irreversible, although
      the magnitude of adsorption was dependent on surface free energy and functional
      group chemistry. Also described is the direct, real-time detection of the binding
      of peptides to HIV-1 TAR RNA bound on a thickness-shear mode (TSM) sensor
      surface. The results clearly indicate that responses are discriminatory for two
      different peptides. In order to provide a theoretical backcloth for the
      experimental measurements, a new model for the operation of the TSM in liquids is
      presented.

PMID- 9569776
TI  - Simultaneous frequency and dissipation factor QCM measurements of biomolecular
      adsorption and cell adhesion.
AB  - We have measured the energy dissipation of the quartz crystal microbalance (QCM),
      operating in the liquid phase, when mono- or multi-layers of biomolecules and
      biofilms form on the QCM electrode (with a time resolution of ca. 1 s). Examples
      are taken from protein adsorption, lipid vesicle adsorption and cell adhesion
      studies. Our results show that even very thin (a few nm) biofilms dissipate a
      significant amount of energy owing to the QCM oscillation. Various mechanisms for
      this energy dissipation are discussed. Three main contributions to the measured
      increase in energy dissipation are considered. (i) A viscoelastic porous
      structure (the biofilm) that is strained during oscillation, (ii) trapped liquid
      that moves between or in and out of the pores due to the deformation of the film
      and (iii) the load from the bulk liquid which increases the strain of the film.
      These mechanisms are, in reality, not entirely separable, rather, they constitute
      an effective viscoelastic load. The biofilms can therefore not be considered
      rigidly coupled to the QCM oscillation. It is further shown theoretically that
      viscoelastic layers with thicknesses comparable to the biofilms studied in this
      work can induce energy dissipation of the same magnitude as the measured ones.

PMID- 9569777
TI  - Positive alveolar and gingival effects of the ALF-LB. Advanced Lightwire
      Functional-lip bumper.

PMID- 9569778
TI  - The prevalence of TMD in orthodontic patients prior to treatment at NCKUH in
      southern Taiwan. National Cheng Kung University Hospital.
AB  - Orthodontic treatment is considered one of the risk factors for temporomandibular
      disorders (TMD). However, TMD may occur before orthodontic treatment. The purpose
      of this study was to investigate the prevalence of TMD in orthodontic patients
      prior to treatment. The samples consisted of 508 patients (214 males and 294
      females) at the National Cheng Kung University Hospital (NCKUH) in southern
      Taiwan. Ages ranged from 6 to 56 years. TMD signs were recorded by clinical
      examination prior to treatment. The overall prevalence of TMD was 26.6%. The
      prevalence was slightly higher in females (27.2%) than males (24.8%). However,
      the difference was not statistically significant. The prevalence of TMD in
      children (ages 6-17) and adults (ages 18-56) was 16.5% and 43.6%, respectively.
      The difference was statistically significant. Distribution of TMD signs was joint
      sounds (32.3%), muscle or joint pains (32.3%), muscle or joint pains (32.3%),
      mouth opening less than 35 mm (18%), combination of two signs (16.5%) and
      combination of three signs (0.8%).

PMID- 9569779
TI  - Advanced lightwire functionals reduce orthodontic relapse factor.
AB  - Past orthodontic research by Schwarze in "Expansion and Relapse in Long Follow-Up
      Studies" concluded "... that orthodontically induced transverse sizes of the
      dental arches are very unstable." The article further stated that, "the majority
      of patients showed a decrease of the transverse molar and canine distance from
      the end of treatment to the follow-up examination." Also emphasized was the fact
      that "prolonged retention periods do not prevent relapses." These findings are
      based on orthodontic techniques that focus on movement of teeth and maxillary
      expansion without regard for existing cranial base and cranial bone distortions.

PMID- 9569780
TI  - Skeletal classification of maxillary and mandibular malpositions.
AB  - Criteria used to establish ideal skeletal position of the maxilla and mandible
      relative to the cranial base is exacting. It must first enhance facial esthetics
      and facial profile. Secondly, it must improve TMJ health; and finally, it must
      improve physiologic harmony. Physiologic harmony include alleviation of many
      medical symptoms such as migraine headaches, neck-shoulder-back pain, myalgia,
      mouth breathing, otitis media, ringing in the ear, dizziness, vertigo, etc. The
      Skeletal Archial Analysis is a powerful diagnostic aid. Once the skeletal
      landmarks are learned, it takes clinicians less than 5 minutes to trace and
      diagnose. This is because it uses visual references rather than columns of angles
      and linear measurements. How powerful and accurate is this analysis? If done
      correctly, patients treated to their anterior arc and correct vertical arc will
      often times achieve significant facial esthetics, TMJ health, and physiologic
      harmony. Both the Skeletal Archial Analysis and the Skeletal Classification
      System indicate whether the disharmony is in the maxilla, mandible, or both. They
      clearly show in which direction these skeletal structures must be moved to
      enhance facial appearance and health. In all cases, the direction is to move
      these structures as close to skeletal Type I, Normal, as physiologically
      possible. Figure 8 shows a 21-year-old female individual with this skeletal
      classification. She has ideal maxillary and mandibular A-P position and ideal
      lower facial height. As can be seen, she has an attractive facial profile and she
      has no clinical symptoms of temporomandibular disorder or other medical problems.
      Conversely, patients with facial disharmony often seem to have various medical
      problems, including premenstrual syndrome and infertility. Once clinicians become
      adept at using the Skeletal Archial Analysis, they will begin to see many more
      types of facial disharmonies than previously thought. It then becomes a verbal
      challenge to accurately describe the multitude of different types of skeletal
      malpositions. In light of this, it is important that a universal Skeletal
      Classification System be established to promote better understanding in the
      diagnosis and treatment of facial-skeletal problems.

PMID- 9569781
TI  - Presentation of individually fit preset elastopositioner (IPE).
AB  - Functioning as an artificial labiolingual duct, the IPE device provides excellent
      guidance for dental eruption during intermediate finishing or retention
      treatment. The IPE device can be relined with flexible, transparent elastomer of
      good mechanical quality, thereby making the appliance individually adaptable to
      any clinical setting, via study casts or directly in the mouth.

PMID- 9569782
TI  - Fluoride concentration and profile in different cementum surfaces.
AB  - This study was performed to determine the fluoride concentration of the various
      cementum surfaces in different tooth groups to find out the most proper teeth and
      tooth surfaces for different cementum studies. For this purpose, direct
      measurements of phosphorus and fluoride were carried out in an acid etch biopsy
      solution. The findings indicate that incisors with exposed cementum are the most
      inappropriate teeth in comparison with the other groups. According to the results
      obtained it may be recommended that the studies related to fluoride uptake for
      cementum should be performed on teeth with no gingival recession or on the
      unerupted teeth.

PMID- 9569783
TI  - Combined use of root conditioning, fibrin-fibronectin system and a collagen
      membrane to treat a localized gingival recession: a 10-case report.
AB  - The purpose of this research was to evaluate the effectiveness of combined root
      surface conditioning with tetracycline HCI, fibrin sealing system, guided tissue
      regeneration procedure and coronal sliding flap application in the treatment of
      localized gingival recessions. The present study was conducted on 10 patients
      with localized facial recessions of at least 3mm. A trapezium-shaped flap was
      elevated apically to the margin of the bone dehiscence and the root surface was
      thoroughly scaled by hand instruments and burs. Tetracycline HCI (pH 1.9)
      solution was then topically applied for 5 minutes and the root surface thoroughly
      rinsed with sterile saline. A collagen membrane was trimmed and shaped to cover
      the entire root surface and later removed and a fibrin sealing system injected
      onto the root surface. Immediately membrane was placed again on the root surface
      without applying any pressure. The flap was sutured in the coronal position to
      completely cover the root surface and membrane. Control group patients were
      treated with only coronal sliding flap operation. Sutures were removed 10 days
      after surgery. Patients were clinically reevaluated 6 months postoperatively. The
      mean amount of root surface coverage obtained was similar in the test and control
      groups (test = 71.7%; control = 68.55%) but the clinical attachment gain (test =
      4.21mm; control = 2.86mm) and pocket depth variations (test = 1.14mm reduction;
      control = 0.07mm reduction) differed significantly (P < 0.001). This study found
      promising healing of localized gingival recessions to result from a combined use
      of tetracycline HCI root demineralization, fibrin sealing system application,
      guided tissue regeneration procedure and coronal sliding flap operation.

PMID- 9569784
TI  - Dental caries prevalence, dietary habits, tooth-brushing, and mother's education
      in 500 urban Turkish children.
AB  - 500 children with ages ranging between 2 and 13 years and their families joined
      the study. A detailed questionnaire and a 3-day food intake diary were evaluated
      to find the relationship between dental caries and dietary habits. It is
      concluded that the prevalence of caries increases by frequent and high sugar
      consumption. With lower age and lower caries experience followed a more balanced
      diet. There was an inverse relationship between caries prevalence and the
      mothers' educational level. The percentage of children who never or irregularly
      brushed their teeth was highest in the caries active group.

PMID- 9569785
TI  - Effect of Cervitec varnish on the salivary Streptococcus mutans levels in the
      patients with fixed orthodontic appliances.
AB  - The aim of the present study was to assess the efficiency of a 1% chlorhexidine
      containing varnish (Cervitec, Vivadent, Liechtenstein) on the levels of
      Streptococcus mutans in saliva of patients with fixed orthodontic appliances
      using the Dentocult-SM (Vivadent, Liechtenstein) technique for the
      microbiological investigation. Eighty subjects participated in the study and,
      divided randomly into two equal groups in which one group was treated with the
      placebo varnish (Vivadent, Liechtenstein) for negative controls. Streptococcus
      mutans in saliva of the subject was sampled and enumerated by using the Dentocult
      SM dip-slide technique for periods of one, two four and twelve weeks after a
      single varnish application. The results were evaluated statistically. After the
      chlorhexidine containing varnish treatment the levels of Streptococcus mutans in
      saliva were significantly reduced after one week (p < 0.01) and continued
      reduction for one month (p < 0.05). After twelve weeks Streptococcus mutans
      levels in saliva were given a relative increase. No significant suppression was
      found in the placebo group (p > 0.05). The results suggested that Cervitec
      varnish reduces salivary Streptococcus mutans levels and that the application
      should be repeated every 3 months to get antibacterial effect.

PMID- 9569786
TI  - An investigation of resorption and tissue reaction after subcutaneous
      implantation of collagen based membrane materials in rats.
AB  - This study was undertaken to assess histologically the response to collagen based
      membrane materials that might be used for guided tissue regeneration (GTR)
      procedures, using a subcutaneous model on the dorsal surface of the rat. The
      commercially available materials included absorbable type I bovine collagen
      barrier, fascia lata, fascia temporalis and dura mater membranes. In the study 20
      Wistar rats were used 80 implant materials were placed under general anaesthesia.
      Animals were sacrificed 7, 14, 28 and 42 days post-implantation. The specimens
      were assessed histologically for the composition of the tissue surrounding the
      membranes, the types of cells in infiltrate and the degree of resorption. It was
      concluded that these membrane materials were well tolerated and were gradually
      resorbed. Light microscopic examination showed that the type I bovine collagen
      and fascia lata were resorbed faster but fascia temporalis and dura mater were
      resorbed more slowly at 42 days. In addition the resorption process was
      continuing and these materials were evident histologically at 42 days.

PMID- 9569787
TI  - Dental caries and Cariostat test in preschool children.
AB  - The aim of this study was to investigate the caries status and susceptibility of
      children in preschool age. Sixty one children ages between 3 to 5 years (mean age
      4.38 +/- 0.71) participated in this study. Caries status was assessed according
      to WHO criteria, and caries susceptibility by using the Cariostat test. The mean
      df-t was found to be 2.28 +/- 0.71 (df-s 6.26 +/- 11.92) and 31 children were
      caries-free. Cariostat scores were 1.75, 2.00, 2.16 in the 3, 4, and 5 year age
      groups respectively. There were no significant differences in caries status or
      Cariostat scores between boys and girls. The df-t for the 5 year age group was
      significantly higher than that for the 3 year age groups (p < 0.05). The test
      found 77% of the children to have a high caries risk (Cariostat score > 2.0).

PMID- 9569788
TI  - Multidisciplinary approaches: esthetic restorations after orthodontic treatment.
AB  - After orthodontic treatment prosthetic restorations are sometimes still necessary
      to improve the patient esthetics. After routine orthodontic procedures (alignment
      of teeth and achievement of functional occlusion) conventional crowns and bridges
      are used. In this case study, the follow-up results of four patients are
      presented. They had been treated by various disciplines; orthodontics, plastic
      surgery and prosthodontics. Satisfactory esthetics and function were achieved
      with all patients.

PMID- 9569789
TI  - Titanium mesh and autogenous iliac bone graft: treatment of a mandibular fracture
      delayed for one year.
AB  - In treatment of bone defects, transplantation of autogenous iliac bone and marrow
      give satisfactory results. Titanium mesh implants have also been used
      reconstruction of maxillofacial defects for years. Specifically, this technique
      of provides stabilization in ununited fractures of edentulous and atrophic
      mandibles, and facilitate bone grafting. This paper report the use of titanium
      mesh and autogenous iliac bone grafting in an ununited mandibular fracture one
      year after injury.

PMID- 9569790
TI  - Granular cell tumour (a case report).
AB  - The granular cell tumour (GCT) is a relatively uncommon neoplasm that shows a
      predilection for the oral cavity, especially the tongue. The tumour usually
      presents as a slow-growing, non-ulcerated nodular mass. It is most common in
      young and middle-aged adults and is twice as common in women as in men. Some
      studies have shown it to be relatively more common in coloured people. Multiple
      granular cell tumours occasionally may occur. Treatment consists of local
      surgical excision; recurrence is uncommon. This case report presents a case of
      GCT in a 32 years old woman's tongue and its treatment.

PMID- 9569792
TI  - Salivary cortisol levels in children during dental treatment.
AB  - Cortisol which is also called as stress hormone, is used as an indicator in the
      stress evaluation studies. 60 children who never visited a dentist before,
      participated in the present study. Saliva samples were collected from 30 children
      without any dental treatment (control group). Experimental group comprised 30
      children with caries. Saliva samples were obtained at various stages during
      dental treatment. Totally 180 samples were collected and the cortisol levels were
      measured. Paired-t test has shown that the salivary cortisol levels at various
      stages of dental treatment in the experiment group were significantly higher in
      comparison with the control group. It is concluded that dental treatment may
      cause extreme stress in children who never had dental treatment experience
      before.

PMID- 9569791
TI  - The effect of a varnish with fluoride on the hardness of the exposed human
      dentine tissue.
AB  - The aim of this study was to evaluate the effect of a new varnish with fluoride,
      Fluoridin N-5, on the exposed dentine tissue in situ. Human incisors which were
      mounted into intra-oral devices were worn by six volunteers and the test
      materials were applied three times a day for fourteen days. Three different
      materials were used as three test groups: Novalite, Fluoridin gel N-5 and Amalgam
      liner. Although both the control and test groups showed some increases in
      hardness, the mean hardness increase of all of the test groups was significantly
      higher than that of the control group (p = 0.007). However, the comparison of
      mean increases in hardness values showed no significant difference among the test
      groups.

PMID- 9569794
TI  - Smooth coronal surface, resin restoration and microleakage.
AB  - The space between the resin and the cavity walls has always become interesting to
      search. The aim of this study was to evaluate any differences on leakage values
      of Class 5 type resin restorations prepared on surrounding surfaces of the tooth
      crown. Ninety human teeth were prepared as Class 5 cavities on buccal, lingual,
      mesial and distal surfaces and were randomly divided into groups for bevelling,
      groove preparation and as control. The subgroups were arranged as fluoride gel
      and/or sealant applications. Fluoride gel was applied following the cavity
      preparations. Sealant was applied over composite resin restorations. Treated
      teeth were thermocycled and immersed into dye solution for 96 hours. The
      restorations were evaluated in a stereo-microscope following the sectioning.
      Bevelling of the cavosurfaces and/or preparation of a groove addition to cavity
      procedures did not make any difference on the microleakage scores of the
      restorations done on either surfaces statistically.

PMID- 9569793
TI  - Colour stability of three esthetic laminate materials against to different
      staining agents.
AB  - The purpose of the present study was to evaluate the colour stability of three
      laminate veneer materials against to tea, coffee and cigarette smoke. 72 discs
      prepared by using two different type composite materials and a dental porcelain
      were divided into groups and immersed into distilled water, tea, Turkish coffee
      solutions. The last group was exposed to cigarette smoke. Colour differences were
      measured by colorimeter at the beginning and then in the period of 1 day, 1 week
      and 1 month respectively. As a result, it was found that cigarette smoke was the
      most staining agent, porcelain material was the most colour stable material, and
      indirect composite material was more colour stable than the direct one.

PMID- 9569795
TI  - Postoperative pain control by single doses of piroxicam administered sublingually
      and aspirin.
AB  - The objective of this study is to evaluate and compare the analgesic efficacy of
      Piroxicam Fast Dissolving Dosage Formulation (FDDF) administered sublingually
      either preoperatively or postoperatively with that of aspirin and placebo.
      Hundred patients, undergoing surgical removal of mandibular third molars were
      given sublingually either piroxicam FDDF 40 mg or placebo or aspirin 500 mg
      according to a double blind experimental model. Pain scores and pain relief was
      recorded hourly for six hours following the operation. Rescue analgesics used
      during the trial and overall assessment of the drug were recorded at the end of
      six hours. Scores were evaluated statistically by student t test. Piroxicam FDDF
      was significantly (p < 0.05) more effective than aspirin and placebo for all
      variables, and less rescue analgesics were required in patients receiving
      piroxicam preoperatively. It was concluded that single doses of piroxicam FDDF
      administered sublingually either preoperatively or postoperatively appeared to be
      effective analgesic for the control of pain after third molar surgery with no
      side effects.

PMID- 9569796
TI  - Keratinization of palatal mucosa beneath metal-based removable partial and
      acrylic-based complete dentures compared with normal palatal mucosa: a clinical,
      cytological and histological study.
AB  - Normal human palatal epithelium is an orthokeratinizing tissue with a well
      developed stratum corneum. Several cytological and histological studies showed
      that when the palate covered by a denture fully or partially, keratinization of
      the mucosa changes. The results of some studies suggested that keratinization
      changes from orthokeratosis to parakeratosis, and there is a reduction in the
      thickness of stratum corneum. Whereas the results of some other studies showed
      increased orthokeratinization. This study was planned to determine changes in
      keratinization of palatal mucosa in denture wearers compared with normal palatal
      mucosa. Keratinization of palatal mucosa was examined by mainly exfoliative
      cytology in three groups. Group-1 consisted of 51 patients wearing metal-based
      removable partial denture; group-2 consisted of 50 patients wearing acrylic-based
      complete denture and group-3 including 57 healthy volunteers who have not been
      wearing denture served as the controls. In each group, the results of exfoliative
      cytology were supported by histological examinations. Statistical results showed
      that either acrylic-based complete or cobalt-chromium-based removable partial
      dentures seem to reduce the quantity and/or quality of the keratin layer. The
      mean values of keratinization and the thickness of stratum corneum were
      significantly lower in the complete denture group than in the partial denture
      group. Furthermore the reliability of exfoliative cytology was confirmed by the
      guidance of histological examination.

PMID- 9569798
TI  - In vitro study of fungal presence and growth on three tissue conditioner
      materials.
AB  - In this study three type of tissue conditioning materials (Visco-gel, Fixo-gel,
      Fitt) are used in vitro to investigate the presence and growth of Candida
      albicans. In vitro test results of different tissue conditioners showed no
      inhibiting effect on Candida albicans.

PMID- 9569797
TI  - Clinical effects of diflunisal and paracetamol in impacted mandibular third molar
      surgery.
AB  - A double-blind, randomized, cross-over study to compare diflunisal and
      paracetamol for postoperative pain, swelling and trismus relief following
      impacted mandibular third molar surgery was designed. 25 patients received one of
      the drugs at one visit and the alternative at the other visit. First doses were
      given two hours preoperatively and continued twice daily for five days. The study
      was carried out to determine the effect of preoperatively used diflunisal on
      postoperative pain after surgical removal of the third molars as compared to
      paracetamol used in a similar manner. The degree of impaction, pain, swelling and
      mouth opening were assessed by standardized methods and possible adverse effects
      were also recorded separately. Statistical analysis was carried out by "Student's
      t test". (p < 0.01 statistically significant).

PMID- 9569799
TI  - In vivo and in vitro evaluation of marginal integrity in ceramic inlays.
AB  - The marginal integrity is an important factor for the long-term success of
      ceramic inlays. The long term clinical performance of porcelain inlays depends on
      a number of factors of which the marginal adaptation is of significant interest.
      The aim of this study was to determine the margin quality of adhesively luted
      sintered porcelain inlays both in vivo and in vitro. MOD cavities without bevels
      were prepared on 10 extracted human mandibular molar teeth. Using the Ducera
      inlay system, inlays were fired on refractory dies and luted with a dual-curing
      composite resin. After polishing, each, tooth was sectioned in buccal/lingual and
      mesial/distal directions and marginal adaptation was assessed microscopically.
      The mean marginal gap of 78.77 +/- 14.85 microns recorded for occlusal margins
      was significantly smaller than that of 128.85 +/- 34.34 microns seen at the
      approximal margins. For in vivo evaluation, 25 fired porcelain inlays, including
      7 onlays, were placed in Class II cavities. The assessment of the marginal
      adaptation of inlays was made according to the scaling system used by Aberg et
      al. (Acta Odontol Scand 1994; 52:140-149). In 19 of the clinical cases, the
      restoration was contiguous with the existing anatomic form. Both in vivo and in
      vitro evaluations showed the margin quality of porcelain inlays to be high.

PMID- 9569800
TI  - Serum antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas
      gingivalis in juvenile periodontitis and adult periodontitis (part I).
AB  - Recent microbiological studies support the concept that specific gram negative
      bacteria play a major role in the etiology and pathogenesis of human chronic
      inflammatory periodontal disease. Actinobacillus actinomycetemcomitans has been
      isolated frequently from juvenile periodontitis and Porphyromonas gingivalis has
      been shown to be a prominent species in adult periodontitis in humans. The
      purpose of this study was to determine levels of the specific antibodies to
      A.actinomycetemcomitans and P.gingivalis in 17 patients with juvenile and 15
      patients with adult periodontitis and 24 healthy subjects. IgG and IgM antibody
      titers against these antigens were determined by enzyme-linked immunosorbent
      assay (ELISA). The levels of antibodies against A.actinomycetemcomitans were
      significantly higher in the juvenile periodontitis compared to the adult
      periodontitis patients and controls. Anti-P.gingivalis antibodies were elevated
      in adult periodontitis compared to juvenile periodontitis patients and controls.

PMID- 9569801
TI  - The effects of periodontal therapy on serum antibody levels to Actinobacillus
      actinomycetemcomitans and Porphyromonas gingivalis (part II).
AB  - Levels of IgG and IgM antibodies were estimated against Actinobacillus
      actinomycetemcomitans and Porphyromonas gingivalis were determined by enzyme
      linked immunosorbent assay (ELISA) in 17 patients with juvenile periodontitis, 15
      with adult periodontitis and 24 healthy controls at the beginning of treatment
      and 3 to 8 months after periodontal therapy. After treatment, antibodies to A.
      actinomycetemcomitans and P.gingivalis had decreased in patients, but the levels
      were still significantly higher than in healthy controls. Whether or not an of
      antibody level against a specific bacteria changes after periodontal treatment is
      however, still debatable.

PMID- 9569802
TI  - The use of a resin-ionomer in varying restorative procedures: case reports.
AB  - The purpose of this paper is to describe the subgingival placement of a resin
      ionomer for several restorative procedures, namely, root resorption, endodontic
      perforation, and root fracture. After endodontic therapy, a combination scallop
      flap (in attached gingiva)-full thickness flap (at affected tooth only) was
      raised to gain access to the lesion and root defect. The root defects were
      prepared with ultra-sonic instruments under an operating microscope and the
      preparations treated with Tenure Dentin Conditioner (DenMat Corporation, Santa
      Maria, CA). The preparations were washed and lightly air-dried, and the Tenure
      All-Purpose Bonding System (Den Mat Corporation, Santa Maria, CA) was placed in
      the prepared areas. Geristore resin-ionomer (DenMat Corporation, Santa Maria, CA)
      was then syringed into the preparations and either light-activated or allowed to
      undergo a chemical set. Once set, the material was finished with fine diamonds
      under water spray. The flap was then sutured to place with Gore-Tex sutures when
      a non-resorbable Gore-Tex membrane (Gore Corporation, Flagstaff, AZ) was used or
      4-0 nylon sutures when resorbable Guidor membranes (Butler Company, Bensenville,
      IL) were used. The sutures were removed after two days. The patients were
      observed weekly for the first month and then monthly until released. No untoward
      effects have been observed during the time frame of this project. All of the
      cases have been responding satisfactorily. CLINICAL SIGNIFICANCE: The cases
      presented indicate that a resin ionomer, Geristore, may be used as a subgingival
      restorative, and may be placed in lesions thought to be unrestorable. Thus, teeth
      may be saved that were previously designated to be extracted.

PMID- 9569803
TI  - Histobacteriology and pulp reactions to long-term dental restorations.
AB  - The prevention of degeneration and necrosis of the endodont is one of the main
      goals of dental treatment. Kerschbaum and Voss (1979, 1981) described that 15% of
      teeth showed negative results to sensitivity testing 10 years after crown
      preparation. Pulpal responses to dental treatment depend on many factors
      including thermal injury, transsection of the odontoblastic process, vibration,
      desiccation of dentin, pulp exposure, smear layer, remaining dentin thickness and
      used materials. The knowledge concerning endodontic reactions in short and medium
      term observation is mainly based on research by Klotzer and Langeland.
      Histological assessment of reactions is a well accepted method for
      biocompatibility testing (i.e. ISO/TR 7405). It is consistent to apply its
      principles to the evaluation of endodontic reactions of teeth with long term
      restorations. As pulpal injury is furthermore due to microleakage between filling
      material and the wall of the cavity the analysis of infected dentin tubules seems
      to be important. A consideration of the location of the tubules and of the
      severity of the invasion is necessary. Using a classification (grade 1-6)
      comprising the parameters of degenerative and regenerative reactions and
      bacterial invasion, 24 teeth restored with different types of fixed prosthodontic
      restorations were investigated. The restorations were between 0-6, 7-12 and 13-18
      years in situ. Serial sections (5 microns) were stained with haematoxylin-eosin,
      azan, according to Goldner and J. Hopkins. 22 of 24 teeth showed typical
      degenerative reactions. Negative sensitivity testing occurred in teeth with no
      pain and no or partial necrosis. The histobacteriological assessment showed
      bacterial invasion of the dentin tubules of 21 teeth. From this investigation it
      was concluded that the proposed classification shows sufficient sensitivity for
      the evaluation of progressive endodontic changes of long-term restored teeth.
      Furthermore it was shown that bacterial invasion must be considered as a possible
      co-factor for the described degenerative character of the pulpal tissue.

PMID- 9569804
TI  - The relation of microbiologic data to aspartate aminotransferase enzyme activity
      in gingival crevicular fluid.
AB  - Gingival crevicular fluid (GCF), reflects the immune and inflammatory reactions
      and is itself a location for specific host-microbe interactions that lead to
      periodontal diseases. Aspartate aminotransferase (AST) is one of the components
      of GCF that is released as a result of cell death. In this study, 40 periodontal
      sites in 10 early onset periodontitis patients before and after nonsurgical
      periodontal therapy, with and without local metronidazole administration, were
      first examined for the AST enzyme levels in GCF and then evaluated for
      microbiological and clinical variables. In each patient, 4 sites (one
      site/quadrant) with a probing depth of > or = 5 mm were selected and treated with
      separate treatment protocols. Certain microbial species including Prevotella
      intermedia, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans(A.
      a.) were found more often and/or in higher levels in AST active sites (36/40
      first measurement--9/36 second measurement), while other species (Streptococcus
      and Actinomyces) were found more often and/or in higher levels in AST inactive
      sites (4/40 first measurement--8/36 second measurement). Eight post-treatment AST
      active sites revealed 1.5 mm of attachment loss, whereas 8 post-treatment AST
      inactive sites showed 1.37 mm of attachment gain. AST activity and
      microbiological-clinical data presenting such an agreement suggests that, AST
      level assessment would be beneficial as an adjunctive method alongside other
      clinical criteria, in guiding the clinician in periodontal treatment.

PMID- 9569805
TI  - A clinical and microbiological evaluation of systemic and local metronidazole
      delivery in early onset periodontitis patients.
AB  - The present study describes selected clinical and microbiological results
      obtained by treatment with local (Elyzol) and systemic (Flagyl) use of
      metronidazole alone and/or mechanical subgingival debridement in early onset
      periodontitis (EOP). Twelve patients, with lesions not distributed as in
      classical localized juvenile periodontitis, were included. They were randomly
      divided into local and systemic treatment groups each comprising 6 individuals,
      in each of whom 4 sites (one site/quadrant) with a probing depth of > or = 5 mm
      were selected and treated with separate treatment modalities. The overall
      treatment design provided 6 different test groups. Groups of quadrants received
      1) scaling and root planing 2) local metronidazole treatment 3) systemic
      metronidazole treatment 4) local metronidazole combined with scaling and root
      planing 5) systemic metronidazole combined with scaling and root planing 6) No
      treatment. The microbiological and clinical effects of treatment modalities were
      monitored over 42 days. The results demonstrated reductions in mean counts of
      obligate anaerobic and capnophilic microorganisms coupled with significant
      improvements in mean clinical measurements (gingivitis, probing depth, attachment
      level) in all groups, except the untreated. Scaling and root planing provided an
      initial clinical improvement with a selective reduction of periodontopathogens
      (92.6% obligate anaerobes, 42.9% capnophilic microorganisms), whereas the
      combination of local or systemic metronidazole with scaling and root planing were
      found superior in reducing capnophilic bacteria (93.7% and 93.4%, respectively).
      It is of critical importance to have a treatment rationale for EOP, since
      bacterial differences exist in the etiological subforms of periodontitis.
      Microbial testing may be justified before prescribing the adjunctive antibiotic
      and selecting the mode of delivery for the successful clinical management of EOP.

PMID- 9569806
TI  - Electron probe analysis of cementum surfaces.
AB  - The purpose of this study was to determine the presence of certain inorganic
      elements in various cementum surfaces. The electron probe analysis appears to be
      the most suitable technique for examining elemental composition within localized
      small areas of mineralized tissue, it was used to determine the mineral contents
      of nondiseased, periodontally diseased and root planing applied diseased cementum
      surfaces were determined by electron probe. Calcium (Ca) and phosphorus (P) were
      the elements searched for. Surface morphological features of these cementum
      surfaces were also examined. Electron probe analysis indicated an elevated Ca and
      P content in diseased cementum surfaces. Root planing of these surfaces did not
      reduce the mineral contents of these root surfaces. Our findings indicate that on
      the cementum surfaces affected by periodontal disease inorganic contents were
      altered and the hypermineralized layer in diseased cementum may play a role in
      preventing total diseased cementum removal by root planing.

PMID- 9569807
TI  - Effect of various demineralizing agents on mineral contents of cementum surfaces
      (an electron probe analysis).
AB  - The purpose of this investigation was to determine the surface morphology and
      mineral content of periodontally diseased cementum surfaces following root
      planing and conditioning with either citric acid, tetracycline HCL and
      minocycline HCL. Mineral contents of cementum surfaces were determined with an
      electron probe. All 3 demineralizing agents caused the exposure of the collagen
      matrix on the root surface but citric acid was the more effective. Calcium (Ca)
      and phosphorus (P) showed higher values in citric acid and minocycline HCL
      treated cementum surfaces compared to nondiseased cementum surfaces. The Ca and P
      were found to be in similar proportions in the tetracycline HCL treated group and
      nondiseased cementum surfaces. Although citric acid is a strong demineralizing
      agent, our specimens' cementum surfaces to which citric acid was treated showed
      high Ca and P content. In our opinion this difference about the effects of
      demineralizing agents on the surface morphology and surface element content was
      found to be related to the facts that whether the total amount of
      hypermineralized cementum as removed or not with root planing and the lacking
      criteria to detects the amount of this removal. Our findings suggest that these
      demineralizing agents can demineralize cementum surface after root planing but
      can not remove all of the hypermineralized diseased cementum. For this reason, it
      may be stated that it is more important to remove the pathologically altered
      cementum than applying various chemical agents.

PMID- 9569808
TI  - Antistreptolysin O, rheumatoid factor and C-reactive protein determination in
      patients with recurrent oral ulcer.
AB  - Recurrent oral ulcer (ROU) is a common disease whose the etiologic factors have
      not yet been identified. Although the autoimmune mechanism due to streptococcal
      antigens may be involved in this disease, serum immunoglobulins are reported to
      be higher than normal controls in various phases of ROU. Oral ulcers are one of
      the criteria in the diagnosis of some systemic diseases such as Wegener's
      granulomatosis, Behcet's syndrome, suppurative arthritis, Reiter's syndrome and
      neutropenias. Any patient with recurring oral ulcers should be evaluated
      medically for the possible presence or future development of serious systemic
      diseases. In this study of the 58% of the ROU patients who had positive ASO
      values, only one female patient had a moderate increase: ++ASO(= 400 IU), the
      rest had a slight increase: +ASO(= 200 IU). In the control group only 3 female
      subjects had +ASO (= 200 IU). The aim of this study was to determine whether
      there is any relationship between ROU and rheumatoid arthritis. Patients with ROU
      were examined for antistreptolysin O, rheumatoid factor and C-reactive protein
      and compared to healthy controls.

PMID- 9569810
TI  - A method for preparing collagen graft materials.
AB  - The aim of this research was to develop a method of local production of collagen
      graft materials which are presently imported. The following methods were used to
      produce collagen membrane and sponge from human placentas and rat tail tendons.
      Collagen type I was isolated from human placenta and rat tail tendon by acetic
      acid extraction and characterised by SDS-PAGE. The collagen sponge was prepared
      by dissolving the collagen in HCl. The resulting dispersion was poured into a
      glass container, freeze-dried and then cross-linked by immersion in
      glutaraldehyde solution. It was then washed with distilled water and freeze-dried
      again. The collagen membrane was also similarly prepared by dispersing
      lyophilized collagen in HCl but then mixed with glutaraldehyde, exposed to U.V.
      light and later air dried.

PMID- 9569809
TI  - Salivary sialic acid and cancer.
AB  - In this preliminary study the salivary sialic acid levels in 56 randomly selected
      cancer patients of different ages were compared with those of 70 healthy controls
      of similar age distribution. The cancer patients consisted of 25 women and 31
      men. Twenty were suffering from lung cancer. Unstimulated whole saliva was
      collected by expectoration. The mean sialic acid levels were 185 +/- 22.8 mg/dl
      in the cancer group and 6.2 +/- 3.72 mg/dl in the controls and the difference
      between them was significant (p < 0.0001). The subjects were also grouped
      according to age and cancer type. However there were no significant differences
      in sialic acid levels between these.

PMID- 9569811
TI  - Nonenzymatic glycosylation of tissue and blood proteins.
AB  - A brief description of the phenomenon of nonenzymatic glycosylation will be
      presented, some examples given from the literature and then a brief summary of
      the results of laboratory research conducted in this area by myself and coworkers
      since 1981. Excessive glycosylation causes undesirable changes in proteins. Such
      glycosylation also occurs to collagen in oral tissue. In a study on induced
      experimental diabetes in rats we observed a defective platelet aggregation curve
      for gingival collagen. Glycosylation of proteins is known to result in functional
      defects, for example hemoglobin acquires an increased affinity for oxygen.
      Glycosylation of rat and bovine lens crystallins has been reported as being an
      important genesis of cataracts in diabetes. Increased glycosylation of
      submandibular collagen has been shown to occur in diabetes. However collagen from
      normal subjects has also been found to show an age related advanced glycosylation
      end product pigment. Increased platelet membrane protein glycosylation has been
      reported and the hyperaggregation typically observed in these cases thought to be
      due to glycosylation. The presence of red cell membrane proteins has also been
      reported and the impairment of red cell function in diabetes has been reported in
      cases of excessive glycosylation. According to some investigators cataract
      formation is prevented by some specific drug which inhibits the glycosylation of
      lens crystallins. Vitamin C has lowering effects on nonenzymatic glycation.
      Dentists should take into account the possibility of glycosylation of oral
      proteins such as collagen in cases of impaired gingiva tooth connection.

PMID- 9569812
TI  - Nutrient intake and dental health in school children.
AB  - Diet refers to the customary allowance of food and drink taken by a person from
      day to day. The diet may affect dental caries by reacting with the enamel surface
      and by serving as a substrate for cariogenic microorganisms. This study examined
      the role of specific nutrients in the caries experience of elementary school
      children. 120 children aged between 6-11, who attended the Pedodontics Department
      of Marmara University, Faculty of Dentistry for routine dental treatment received
      a dental examination, parent interview, and a 3-day diet diary. The diary was
      completed adequately for 100 children (83%). The average daily intake of
      nutrients were computed and total sugar consumption and Ca/P ratio were
      calculated. Each child's gender, age, fluoride history, socio-economic state of
      the family, previous dental experience, brushing habit, and nutrient intake were
      examined as independent variables. No association was apparent between dental
      caries and the intake of specific nutrients or Ca/P ratio, except with total
      sugar consumption.

PMID- 9569813
TI  - Relationship between various functional impression techniques and different
      operators.
AB  - The purpose of the present investigation was to determine the relationship
      between the reproducibility of soft tissue contours by three different functional
      impression techniques and four dentists for mandibular distal-extension removable
      partial dentures. The selected functional impression methods were Lejoyeux, Rouot
      and McLean techniques. A mucostatic impression technique was used for the control
      group. To compare and measure the degree of tissue displacement, a three
      dimensional coordinate measuring system was used. The differences in vertical
      displacement of soft tissue among the operators were statistically determined for
      each impression technique used. Lejoyeux technique produced the least variation
      in tissue displacement followed respectively by McLean, mucostatic and Rouot
      methods.

PMID- 9569814
TI  - Evaluation of coronal microleakage of four different glass-ionomer cements in
      endodontically treated teeth.
AB  - Four different glass-ionomer materials were evaluated for coronal microleakage in
      permanent lingual access restorations of endodontically treated anterior teeth.
      Forty extracted human anterior teeth were randomly divided into four groups
      following chemomechanical preparations and obturations with gutta-percha and
      sealer. Logobond, Aqua Ionobond, Ionoseal and Ketac-Cem were placed in 2 mm
      thickness over the gutta-percha obturation from cemento-enamel junction. Eight
      teeth were used as negative and positive controls. The teeth were thermocycled,
      coated with nail varnish and paraffin except around the access preparation. Next
      they were placed in dye and cleared to allow visualization of dye penetration.
      There was a tendency for the Ketac-Cem group to lack least but there were no
      statistically differences among the groups.

PMID- 9569815
TI  - Acute maxillary sinusitis from a dental implant: an unusual case report.
AB  - In this case report, we present an unusual complication of a previously inserted
      dental implant leading to maxillary sinusitis. The implant was removed and the
      patient postoperatively prescribed antibiotic medication. At the follow-up
      examination, healing was observed without any complications.

PMID- 9569816
TI  - Radiological assessment of elongated styloid process and ossified stylohyoid
      ligament.
AB  - In this study a radiological assessment of elongated styloid processes and
      ossified stylohyoid ligaments was performed on 900 panoramic radiographs of 900
      patients. The styloid process(s) were found to be longer than 30 mm in 12 cases;
      in 8 of these cases elongation was bilateral, and in 4 cases it was unilateral,
      making a total of 20 elongated processes out of a possible 1800--an incidence of
      1.1%. The mean length of the elongated processes was 48.15 mm. Symptoms were
      present in one case of bilateral elongation.

PMID- 9569817
TI  - An investigation of the effects of the local use of 1:25 dihydroxycholecalciferol
      (1:25 D) on tension sites during experimental tooth movement in rats.
AB  - The aim of this work was to investigate the local effects of 1:25 dihydroxychole
      calciferol, one of the most potent osteoclastic activity stimulants. Tests were
      conducted on 32 Wistar albino rats divided into 3 groups: an experimental
      (appliance + drug, n = 11), control (appliance only, n = 11) and a no therapy
      group (n = 10) which was used for purposes of interpreting histological findings
      in the others. A significantly higher area of unilateral apposition, relative to
      the control group, was observed in the experimental group local to the area of
      administration of the 1:25 D.

PMID- 9569818
TI  - The relations between alveolar ridge and the teeth located in neutral zone.
AB  - The neutral zone is defined as the area where the forces of the tongue pressing
      outward are neutralized by the forces of the cheeks and lips pressing inward. In
      this study records of neutral zones of 30 edentulous patients were used to
      establish the relation between teeth arrangement according to neutral zone
      principles and teeth arrangement according to crest of ridge. These 30 patients
      were classified according to their ages, edentulous periods and denture
      experience. The results have shown that the lower molars were positioned a little
      bit closer to lingual with respect to crest of ridge; premolars were positioned
      either close to crest of ridge or they were coincided on it. In the anterior
      zone, the teeth were in accordance with known principles of positioned of
      anatomic landmarks.

PMID- 9569819
TI  - Dental implants: anatomy on cross-sectional tomograms.

PMID- 9569820
TI  - Malpractice lawsuits as related to subsequent treaters.

PMID- 9569821
TI  - Community water fluoridation in Louisiana: an update.

PMID- 9569822
TI  - Maintenance of automatic dental film processors.

PMID- 9569823
TI  - Sleep disordered breathing. The dentist's role in diagnosis and therapy.

PMID- 9569824
TI  - Informed consent. Forewarned is forearmed.

PMID- 9569825
TI  - Care of the cleft patient: an overview.

PMID- 9569826
TI  - Computers in the toolbox: automating your practice.

PMID- 9569827
TI  - Managed care: educate and advocate.

PMID- 9569828
TI  - Stress and dentistry: better practice through control.
AB  - It's impossible to give a single definition to stress. That's because people
      experience it in different ways. It is possible, however, to get it and keep it
      under control. In fact, stress control is necessary to every successful dental
      practice.

PMID- 9569829
TI  - Case presentation: pyogenic granuloma.

PMID- 9569830
TI  - Case presentation: globulomaxillary cyst.

PMID- 9569831
TI  - Pseudocyst of the maxillary sinus.

PMID- 9569832
TI  - Multiple lesions of the mandible.

PMID- 9569833
TI  - Case presentation. Ulcer of palate.

PMID- 9569835
TI  - AIDS growth disturbing.

PMID- 9569834
TI  - Case presentation: latex allergy.

PMID- 9569836
TI  - Case presentation. Initiation of gingival overgrowth by an increased daily dosage
      of nifedipine.

PMID- 9569837
TI  - Knowledge and perception about AIDS transmission.

PMID- 9569838
TI  - Case presentation. Alveolar ridge mass of a newborn.

PMID- 9569839
TI  - Infection control in Mississippi dental practices: a comparison of Mississippi
      Dental Association members and non-members.
AB  - In conclusion, the results of the survey were reassuring in many ways. The data
      indicate that the dental profession in Mississippi seems to have taken advantage
      of continuing education opportunities, paid increased attention to infection
      control, and in general, were using appropriate techniques before the OSHA
      mandate of 1992. Furthermore, members of the MDA not only demonstrated a greater
      understanding of infections diseases, but were also 20 percent more likely to
      report behavior known to reduce the risk of cross infection. It will be important
      to continue to identify the "gaps" and provide information, additional training,
      and encouragement to the dental profession and to dental auxiliaries to improve
      infection control procedures where improvement appears to be needed.

PMID- 9569840
TI  - Case presentation. Pyogenic granuloma with an unusual clinical behavior.

PMID- 9569841
TI  - Differential diagnosis of a minor salivary gland tumor.

PMID- 9569842
TI  - Case presentation. Denture-induced fibrous hyperplasia (epulis fissuratum).

PMID- 9569843
TI  - Single tooth implant: a unique restoration.

PMID- 9569844
TI  - Getting to the root of the problem.

PMID- 9569845
TI  - "Implant hygiene maintenance and repairs".

PMID- 9569846
TI  - Case presentation. Polymorphous low-grade adenocarcinoma: a minor salivary gland
      malignancy with benign clinical features.

PMID- 9569847
TI  - Salivary gland tumors in Mississippi.

PMID- 9569848
TI  - Case presentation. Bilateral parotid gland enlargement.

PMID- 9569850
TI  - New HIV test.

PMID- 9569849
TI  - The Bass technique: Charles Cassidy Bass' legacy.
AB  - Charles Cassidy Bass a native Mississippian introduced his method of
      toothbrushing and flossing to the dental community four decades ago. He chastised
      the academic, public health and military dentists for their lack of knowledge in
      area of preventive dentistry. Dr. Bass felt that his "Right Kind" method of oral
      hygiene was not well received by the dental profession. A questionnaire was sent
      to every United States dental school to determine what effects his teachings had
      on dental education. The study revealed that C. C. Bass' teachings were indeed
      accepted by the dental profession and are still in effect today.

PMID- 9569851
TI  - Case presentation. Multiple flattened papules of the oral cavity.

PMID- 9569852
TI  - In-vitro microleakage of enamel etched with an airbrasive.

PMID- 9569853
TI  - Implant dentistry: a success? Yes! (an analysis of one oral surgeon's first one
      thousand implants).

PMID- 9569854
TI  - Case presentation: leukemia in a child.

PMID- 9569855
TI  - Gingival blood flow.
AB  - In the oral cavity extensive vascular changes accompany progression of gingival
      inflammation or healing and remodeling of periodontal tissues. This study was
      designed to explore how the gingival capillary circulation might be influenced by
      mechanical stimuli; specifically, tooth brushing. Changes in blood flow
      subsequent to mechanical stimulus of brushing were measured by laser Doppler
      flowmetry at the midline, canine and premolar regions of maxillary and mandibular
      arches. Results showed that tooth brushing increased the blood flow in these
      regions by approximately 60 percent relative to the resting state. These changes,
      however, were shortlived. Fifteen minutes following this mechanical stimulus the
      capillary circulation returned back to within ten percent of baseline readings.
      We conjecture that frequently applied mechanical stimuli might aid in gingival
      remodeling, high tissue turnover and metabolic rate.

PMID- 9569856
TI  - The sharing page.

PMID- 9569857
TI  - Getting to the root of the problem.

PMID- 9569858
TI  - Caries in minority children ages 1-4 in Baltimore and Washington.

PMID- 9569859
TI  - Oral health care and the elderly in Maryland.

PMID- 9569860
TI  - Audit of clinical information and diagnoses supplied to the pathologist following
      biopsy of oral squamous cell carcinomas.
AB  - Strict criteria for the biopsy of oral lesions suspected to be squamous cell
      carcinoma (SCCA) are difficult to find. Evaluation of the patient's history and
      clinical findings should help the clinician to accurately diagnose oral cancer.
      Our study attempts to compare and correlate cases that have the histopathologic
      diagnosis of oral SCCA with the data submitted by the clinician to the oral
      pathologist. We find the more information the clinician lists in the biopsy
      request form, the more likely the correct clinical diagnosis of oral SCCA is. We
      also show that when risk factors such as tobacco and alcohol use are mentioned by
      the clinician, the percentage of correct clinical diagnosis is increased.

PMID- 9569861
TI  - Oral effects of AIDS.

PMID- 9569862
TI  - The inaugural exhibition of the Dr. Samuel D. Harris National Museum of
      Dentistry: 32 terrific teeth.

PMID- 9569863
TI  - Authoritative note on the founding of the Baltimore College of Dental Surgery.

PMID- 9569864
TI  - A word well lost.

PMID- 9569865
TI  - The Bulletin of the MSDA: this publication's predecessor.

PMID- 9569866
TI  - Predictable adhesion to dentin and enamel.

PMID- 9569867
TI  - Clinical pathology case conference. Multiple myeloma.

PMID- 9569868
TI  - Variable confounding and the influence of non economic determinants on dental
      utilization for the elderly.
AB  - The purpose of this study is to test the hypothesis that variable confounding
      will cause discrepancies in dental utilization analysis and to determine the
      significance of gender, health status, and race on dental utilization by
      controlling for several predictor variables previously reported to be associated
      with dental care utilization. Results provide supporting evidence that
      discrepancies in dental utilization analysis can occur as a result of variable
      confounding. In addition, parameter estimates indicate that older women and white
      adults were more likely to visit a dental office than either older men or older
      blacks. On the other hand, older adults reported to be in poor health were no
      more likely to visit a dentist than older adults in excellent health.

PMID- 9569869
TI  - Malignant lymphoma presenting as periapical pathology: a report of two cases.

PMID- 9569870
TI  - Improvements in impression materials give more predictable results.

PMID- 9569872
TI  - Comparison of two film holders for periapical radiography performed by dental
      students.
AB  - A clinical study was done at Howard University, College of Dentistry, to compare
      the difference in the incidence of radiographic technique faults between two
      similar intraoral film-holding, beam-aligning, devices in a series of 1,248
      radiographs. The primary difference between a conventional Extension Cone
      Paralleling (XCP-I) film holder and a modified, all-metal, Extension Cone
      Paralleling (XCP-II) film holder is the incorporation of a collimated rectangular
      x-ray-beam-restricting plate. This latter film holder possessed an indicator rod
      attached to the bite block and a metal shield to reduce primary and back
      scattered radiation behind the film. In the oral diagnosis clinic, 78 dentulous
      patients were randomly selected and randomly divided into two groups of 39
      patients. One of the two film holders was used separately for the two groups of
      patients, and a full mouth series of 16 periapical radiographs were made for each
      patient. The difference in the occurrence of total errors between the two
      instruments was not statistically significant. However, the conventional
      instrument was associated with significantly more errors in improper film
      positioning, while the modified device had significantly more errors in cone
      cutting (p < 0.01).

PMID- 9569871
TI  - Clinical pathology case conference. Infectious mononucleosis.

PMID- 9569874
TI  - Subperiosteal implants provide another option for dentistry: one practitioner's
      experience.
AB  - Many options are available to patients to maintain occlusal function. Dental
      implants provide yet another. This paper examines the author's experience with
      one type of dental implant technique. The findings are based on data contained
      within the data base the author maintains of approximately 3,000 individual
      implants. The maxilla is the more challenging of the two arches, and the
      subperiosteal allows us to choose between grafting procedures and endosseous
      implants or a combination of subperiosteal implant and root form implants. Each
      has its positives and negatives. The At Risk statistical computer analysis of the
      author's database validates the use of the subperiosteal as an alternative.

PMID- 9569873
TI  - Evaluation of a one-day AIDS continuing education course.
AB  - The effectiveness of a one-day acquired immune deficiency syndrome (AIDS)
      continuing education course for dentists and hygienists was evaluated using
      pretest, posttest, and six-month follow-up questionnaires. There was a general,
      though not statistically significant, increase in the percentage of respondents
      who reported they planned to be immunized against hepatitis B, and a
      statistically significant increase in dentists' perceptions of the percentage of
      their patients at risk for AIDS. The percentage of respondents who believed the
      private practice setting is the preferred practice site for treating healthy
      patients with human immunodeficiency virus (HIV) increased, though the increase
      was not statistically significant. Six-month follow-up results found a
      significant increase in the percentage of respondents who reported being
      immunized against hepatitis B. Other posttest results were maintained at the six
      month follow-up. These results support the contention that a traditional lecture
      approach in AIDS continuing dental professional education can be beneficial.

PMID- 9569875
TI  - Russell-Silver syndrome: review of literature and report of a case.

PMID- 9569876
TI  - The Dentists' Well-Being Committee of Maryland.
AB  - The Maryland Dentist's Well-Being Committee was formed in 1980 as a standing
      committee of the Maryland State Dental Association. The committee has assisted
      many dentists over the years with problems such as stress, alcoholism, drug
      dependence, psychiatric disorders, medical problems, HIV (human immunodeficiency
      virus) disease, neurological disorders, and other illnesses that cause
      impairment. Key elements of the committee include confidentiality, a good working
      relationship with the Maryland State Board of Dental Examiners, advocacy efforts,
      and a paid clinical coordinator with special expertise in mental health and
      addiction treatment.

PMID- 9569877
TI  - Dr. X: the consequences of untreated addiction.
AB  - The following case example shows the difficulty dentists face when their alcohol
      or drug dependence causes them to violate laws or the Dental Practice Act. In
      this case, the dentist is charged with driving while intoxicated (DWI) and is in
      possession of inappropriately prescribed medications.

PMID- 9569878
TI  - Types of impairment among dentists.
AB  - The most common causes of impairment among dentists are cognitive impairment,
      physical disability, chemical dependency, other addictions, and mental illness.
      The most frequently cited cause of impairment for dentists is chemical
      dependence. From 70% to 90% of the individuals reported to state rehabilitation
      committees are reported for chemical dependence. This paper reviews the nature of
      these types of impairments, describes treatment issues in each case, and suggests
      preventive measures.

PMID- 9569879
TI  - Dentistry, stress, and substance abuse.
AB  - Dentists have to deal with many significant stressors in their personal and
      professional lives. It is important for dentists to learn to cope and deal with
      these stressors and their effects. This paper reviews the nature and causes of
      addictions, the relationship between addiction and stress, and methods to
      organize and reduce stress in work environments.

PMID- 9569880
TI  - Management of the active or recovering chemically dependent dental patient.
AB  - To identify chemically dependent patients, dentists should explore whether the
      patients have any history of, or are recovering from, chemical dependency.
      Occasionally, dental treatment plans must be modified for active or recovering
      chemically dependent patients. Dentists need to be alert for chemically dependent
      patients who are doctor-shopping and present themselves to dentists to secure
      narcotic analgesics. Dentists should be aware that chemical dependency is a
      disease, and the management of chemically dependent patients may require certain
      adjustments.

PMID- 9569881
TI  - The advantages of the disease model.
AB  - Health care professionals are interested in practical definitions that provide
      solutions to problems. There are many advantages to defining chemical dependence
      as a disease. This paper gives a health care professional clear directions
      regarding identifying the problem of chemical dependence and specifying a
      specific treatment plan for patients. We review the issues of personal
      responsibility, the moral model of addictions, and the neuropharmacology of the
      disease process, and advocate for the disease model as an effective, practical
      method for treating alcoholism and drug dependence.

PMID- 9569882
TI  - Substance abuse education at the University of Maryland Dental School.
AB  - The Baltimore College of Dental Surgery, Dental School, University of Maryland at
      Baltimore offers an extensive curriculum for the study of substance abuse,
      alcoholism, and other chemical dependencies. This article outlines the curriculum
      course hours and topics of study for both dentists and dental hygienists. The
      goal of the curriculum is for students to understand the disease process,
      intervention methods, treatment options, and other aspects of chemical
      dependence.

PMID- 9569883
TI  - The Maryland State Board of Dental Examiners and the chemically dependent
      dentist.
AB  - The Maryland State Board of Dental Examiners (SBDE) has adopted the disease model
      in dealing with chemically dependent dentists. SBDE has found that a punitive
      attitude toward chemical dependence is not productive. The SBDE works closely
      with the Dentists' Well-Being Committee of the Maryland State Dental Association
      to help dentists regain productive lives while observing its responsibility to
      protect the public. The SBDE's concern for patient welfare is a top priority, but
      it does not lessen SBDE's compassion for dentists who may be suffering from this
      illness.

PMID- 9569884
TI  - Pharmacy surveys.
AB  - The Division of Drug Control, Maryland Department of Health and Mental Hygiene,
      conducts approximately two pharmacy surveys per month on health care
      practitioners. These surveys determine whether a practitioner has prescribed
      controlled and dangerous substances appropriately. In some cases, dentists who
      may be suffering from drug dependence are identified through these pharmacy
      surveys and referred to the Maryland State Board of Dental Examiners (SBDE). In
      addition to this disciplinary process, the SBDE may refer dentists to the
      Dentists' Well-Being Committee of the Maryland State Dental Association for
      evaluation and treatment. This paper reviews the procedures for requesting and
      conducting pharmacy surveys.

PMID- 9569885
TI  - Developing support programs for dentists with infectious disease.
AB  - The American Dental Association (ADA) has developed many resources to address
      growing concerns regarding HIV (human immunodeficiency virus) issues in dental
      practice, including continuing education courses, workshops, journal articles,
      and monographs. In addition, the ADA Council on Dental Practice has established a
      network for dentists with HIV/AIDS (acquired immune deficiency syndrome). The
      network has been named PEERS, which stands for Prevention, Education, Ethics,
      Resources, and Support. This paper provides guidelines for developing programs in
      each state to address the needs of dentists with HIV/AIDS.

PMID- 9569886
TI  - Maryland Dental Hygienists' Association Rehabilitation Committee.
AB  - The Maryland Dental Hygienists' Association Rehabilitation Committee was formed
      in 1990 and is patterned after the Maryland State Dental Association (MSDA)
      Dentists' Well-Being Committee. The Rehabilitation Committee serves to assist
      dental hygienists who may be impaired by alcohol or drug abuse; chemical
      dependency; or other physical, emotional, or mental conditions.

PMID- 9569887
TI  - Tourette's disorder with and without obsessive-compulsive disorder in adults: are
      they different?
AB  - Clinical research has documented a bidirectional overlap between Tourette's
      disorder (TD) and obsessive-compulsive disorder (OCD) from familial-genetic,
      phenomenological, comorbidity, and natural history perspectives. Patients with
      Tourette's disorder plus obsessive-compulsive disorder (TD + OCD), a putative
      subtype, share features of both. The purpose of this exploratory study was to
      evaluate correlates of patients with TD, OCD, and TD + OCD to determine whether
      TD + OCD is a subtype of TD, OCD, or an additive form of both. Sixty-one subjects
      with TD, OCD, or TD + OCD were evaluated with the Structured Clinical Interview
      for DSM-III-R supplemented with additional modules. The three groups differed in
      the rates of bipolar disorder (p < .04), social phobia (p < .02), body dysmorphic
      disorder (p < .002), attention deficit hyperactivity disorder (p < .03), and
      substance use disorders (p < .04). These findings were accounted for by the
      elevated rates of the disorders in the TD + OCD group compared with the TD and
      OCD groups. These finding are most consistent with the hypothesis that TD + OCD
      is a more severe disorder than TD and OCD and may be more etiologically linked to
      TD than to OCD. These findings highlight the importance of assessment of the full
      spectrum of psychiatric comorbidity in patients with TD and OCD.

PMID- 9569889
TI  - Predicting schizophrenic outpatients' behavior by symptomatology and social
      skills.
AB  - Though social skills have been identified as an independent construct, recent
      studies have revealed that schizophrenic symptomatology and social skills are
      interrelated. The nature and extent of this relationship, however, are far from
      clear. To address this issue, we examined 33 schizophrenic outpatients
      participating in a rehabilitation program for an average of 10 months. The object
      of this study was to investigate to what extent behavior can be predicted by
      symptomatology and social skills, and whether social skills have a significant
      effect on outpatients' behavior independently of schizophrenic symptoms and vice
      versa. Regression analyses revealed good prediction of outpatients' behavior by
      conceptual disorganization and disorder of relating from the PANSS and, to a
      lesser degree, social skills. After having eliminated the influence of
      psychopathology on social skills and behavior, social skills variables still had
      significant predictive value for social competence, social interest, and
      irritability. These findings imply specific contributions of both symptomatology
      and social skills to future behavior of chronic schizophrenic outpatients.

PMID- 9569888
TI  - Course of acute affective disorders in a developing country setting.
AB  - This report on the Chandigarh Acute Psychosis Study examines the early course of
      affective disorders of acute onset in a developing country setting. Forty-one
      cases of acute onset affective disorder (17 depressive and 24 manic subjects)
      were assessed at intake and evaluated at selected intervals up to 1 year. The
      rates of recovery and relapse and episode duration were determined for both the
      depressive and manic groups, and the relationship between possible predictors of
      outcome and the duration of the index episode was examined. All subjects
      experienced full recovery within the 1-year period. At 1-year follow-up, 71% of
      depressive patients and 75% of manic patients demonstrated no symptoms or social
      impairment. For depression and mania, respectively, the mean episode duration was
      14.2 and 10.2 weeks, and the rate of relapse was 18% and 21%. Overall, these
      outcomes are considerably more favorable than in comparable studies of affective
      disorders in developed settings. Our findings suggest that acuteness of onset may
      be a major prognostic factor in predicting the course of affective disorders.

PMID- 9569890
TI  - Effects of compensation-seeking on treatment outcomes among veterans with
      posttraumatic stress disorder.
AB  - The desire to acquire or increase financial compensation for a psychiatric
      disability is widely believed to introduce a response bias into patients' reports
      of their symptoms and their work performance. The hypothesized effects of
      compensation-seeking in inhibiting improvement from treatment are examined. Data
      from outpatient (N = 455) and inpatient (N = 553) programs for the treatment of
      posttraumatic stress disorder and associated disorders in the Department of
      Veterans Affairs were used to compare outcomes for veterans who were and were not
      seeking compensation. Outcome was measured as pre/post improvement in symptoms
      and work performance over the course of 1 year after the initiation of treatment.
      No compensation-seeking effect was observed among outpatients, but a significant
      effect was found for some inpatients. The effect for inpatients was manifested
      essentially by patients in a program type which was designed to have an extremely
      long length of stay, thus triggering a virtually automatic increase in payments.
      Like outpatients, inpatients in programs with a moderate length of stay did not
      manifest a compensation-seeking effect on improvement. Although not permitting a
      definitive explanation, the preponderance of the evidence favors the
      overstatement of symptoms rather than either the severity or the chronicity of
      the disorder as the most likely explanation for the compensation-seeking effect
      that was observed. For patients treated in standard outpatient and short-stay
      inpatient programs, compensation does not seem to affect clinical outcomes
      adversely.

PMID- 9569891
TI  - Prisoner of war experience: effects on wives.
AB  - The aim of this study was to compare the wives of Australian soldiers who had
      been imprisoned during World War II (POWs) with a control group of non-POWs'
      wives and also to compare the POWs and non-POWs themselves in respect to several
      psychological and family life characteristics on which differences might be
      expected to arise from the long-term effects of imprisonment. A random sample of
      145 of these veterans and their wives completed several self-administered mood
      and family life scales, an inventory of somatic symptoms, questions about the
      impact of the war on the veteran in the postwar decades, and several social
      background questions. The POWs themselves were more depressed and reported more
      somatic symptoms and a greater postwar impact of the war than the non-POWs.
      However, these differences were not accompanied by concomitant differences among
      their wives. There was some evidence of an influence of the POW's mood on his
      wife's mood in significant correlations between husbands' and wives' depression
      and anxiety scale scores in POW couples alone. Otherwise, there was very little
      indication that the POW experience had any long-term effect on the marriage
      relationship as measured by the variables included in this study.

PMID- 9569892
TI  - Defensive functioning predicts improvement in major depressive episodes.
AB  - We investigated the predictive effect of psychological defenses on the course of
      major depression in a subsample of psychiatric patients from a larger study. We
      tested the hypothesis that a group of eight defenses, associated with depression
      in previous research, would predict, outcome of major depression. After an intake
      interview, 37 patients were rated on all DSM-III-R Axes, the SCL-90-R, and 28
      defenses, using the Defense Mechanism Rating Scales. At 6-month follow-up
      interview, SCL-90-R and Global Assessment and Functioning (GAF) were redetermined
      on 34 (92%), 16 of whom had major depression at intake. Overall Defensive
      Functioning (ODF) significantly predicted GAF at 6-month follow-up over and above
      initial level of global functioning and presence of a personality disorder. The
      group of eight defenses were identified more often (p = .068) in depressed
      patients who improved less than predicted by their initial functional status. The
      high adaptive level defense, self-observation, was identified more often in those
      who improved more than predicted by their initial status. Our findings support
      the theory of a hierarchy of defenses, and the mediating effects of specific low
      and high adaptive level defenses on the course of a major depressive episode.
      Further research should examine passive aggression, acting out, help-rejecting
      complaining, splitting of self-images, splitting of others' images, projective
      identification, projection, and devaluation in relationship to the onset, course,
      and treatment response of depressive disorders.

PMID- 9569893
TI  - A prototypic nonprototype of a personality disorder.
AB  - The prototype model has been suggested as an alternative to the traditional
      categorical model of classification. A series of studies have been performed by
      Blashfield and his colleagues to identify cases that are prototypic of the DSM
      III-R personality disorders. A case that led to diagnostic disagreement was based
      on the 1985 German movie Zuckerbaby ("Sugarbaby"). In earlier research, the most
      popular diagnosis for the case was dependent personality disorder, although
      schizoid, schizotypal, and borderline were almost as frequent. In the current
      study, the case was presented in cumulative steps to 93 randomly selected
      clinicians. After each step was presented, clinicians were asked to diagnose the
      case. With the stepwise presentation format, borderline personality disorder was
      the most common diagnosis. Chi-square analysis showed that, if clinicians had
      chosen borderline as a diagnosis by step three, they were likely to keep this
      decision for the rest of the case. A social-cognitive model was used to explain
      these results.

PMID- 9569895
TI  - Patients with panic attacks seeking care from family physicians compared with
      those seeking care from psychiatrists.

PMID- 9569894
TI  - Lipreading in prelingually deaf and hearing patients with schizophrenia.

PMID- 9569896
TI  - [Infectious diseases: almost 60 years of antibiotic use].

PMID- 9569897
TI  - [Invasive infections by Streptococcus viridans (oral streptococci) excluding
      pneumococci].

PMID- 9569898
TI  - [Problems caused by antibiotic resistance of Helicobacter pylori].

PMID- 9569899
TI  - [Clinical implications of antibiotic resistance of enterococci].

PMID- 9569901
TI  - [Cleansing of medical materials from bacterial adhesions: how effective is it?].

PMID- 9569900
TI  - [Aeromonas infections].

PMID- 9569903
TI  - [Antibiotic therapy of pregnant women].

PMID- 9569902
TI  - [Haemophilus influenzae infection in children: current aspects].

PMID- 9569904
TI  - [Antibiotic therapy in renal insufficiency].

PMID- 9569905
TI  - [Ceftriaxone: pharmacokinetics, pharmacodynamics. Application in the treatment of
      acute otitis media in children].

PMID- 9569906
TI  - [Relieving the obstruction caused by malignant tracheobronchial tumors under
      flexible endoscopy].
AB  - OBJECTIVES: We evaluate the feasibility and the efficiency of electrosurgery in
      the treatment of the symptomatic malignant tracheobronchial tree obstructions
      (MTTO) when it is used with flexible fiberoptic bronchoscopy without general
      anesthesia. METHODS: The aim of electrosurgery was to restore the permeability of
      the tracheobronchial tree to suppress symptoms. The operation lasted no more than
      60 minutes, and a second operation was performed 8 days later if symptoms
      persisted. The patients received local anesthesia and light sedation (midazolm).
      PATIENTS: 28 patients have been treated from june 1995 to june 1996 for following
      symptoms: dyspnea (22 cases), cough (1 case), dyspnea and cough (5 cases). All
      patients had malignant disease palliatively treated. RESULTS: The protocol has
      failed in one case, needing general anesthesia. 27 patients have had one session,
      6 a second one week later. After the first session, dyspnea was improved in 22/27
      cases (81.5%) and cough in 5/6 cases (83%). After the second session, dyspnea was
      globally improved in 26/27 cases (96%), without change for cough. CONCLUSION:
      Electrosurgery is a feasible and safe treatment which can implement immediately
      without general anesthesia, in MTTO. Its result are highly effective on dyspnea
      but less on cough, with reproducible effects and a well-tolerated procedure.
      Further investigations need to compare the different techniques.

PMID- 9569907
TI  - [Repeated thyroid surgery. Indications and results].
AB  - OBJECTIVES: To analyze the histology results and to assess operative risk of
      iterative operations for thyroid surgery. PATIENTS AND METHODS: A total of 249 re
      operations were performed in 248 patients over a 6.5 year period. Two groups of
      patients were defined according to the indications for re-operation. Group 1: 80
      patients; pathology examination of the surgical specimen discovered thyroid
      cancer. Group 2: 169 patients; recurrent nodular goitre after an initially benign
      disease. RESULTS: In group 1, 14 cancers were bilateral (17.5%) and 7 patients
      had cervical node metastases (8.8%). In group 2, 19 cancers were discovered
      (11.1%), including 5 cases with cervical node invasion (26.3%) and 4 with
      visceral metastases (21.1%). Twenty complications occurred in 20 patients (8%):
      compressive cervical hematomas (n = 3, 1.2%), recurrent nerve palsy (n = 7,
      2.8%), hypoparathyroidism (n = 9, 3.6%; including 3 definitive cases, 1.2%) and
      mediastinitis (n = 1). These complications were significantly more frequent in
      patients re-operated for hyperthyroidism or those who had a past history of more
      than one cervicotomy. CONCLUSION: The frequency of bilateral cancer justifies
      completing thyroidectomy after partial thyroidectomy. The rate of definitive
      complications after re-operations is greater than first line cervicotomy but is
      low enough to allow iterative surgery using rigorous procedure in selected
      patients.

PMID- 9569908
TI  - [Rhabdomyolysis in patients with preexisting myopathy, treated with antilipemic
      agents].
AB  - BACKGROUND: Lipid lowering drugs (fibrates and statins) are generally well
      tolerated and side effects, mainly hepatic and muscular disorders are rare.
      However, when they occur, muscular disorders may be severe, leading to
      rhabdomyolysis. We report here four cases of rhabdomyolysis in patients given
      lipid lowering drugs and who had pre-existing myopathy. CASE REPORTS: The four
      patients complained of muscle pain after treatment with niacin, HMGCoA
      inhibitors, as well as fibrates. The myopathy was not recognized at the time of
      prescription in three cases. Myopathy resolved rapidly upon discontinuation of
      the drugs and none of the patients developed renal failure. DISCUSSION: This is
      the first report of rhabdyomyosis induced by lipid lowering drugs in patients
      with pre-existing myopathy. Drug induced myopathy is a known complication of
      lipid lowering drugs either alone or in patients with other conditions such as
      renal failure, immunosuppressive therapy for cardiac transplantation, or in case
      of combination regimens. Such a side effect without concomitant disease has not
      been reported previously in patients with congenital myopathy. Cholestyramine is
      the drug of choice for these patients. Our observations suggest that the
      rhabdomyolysis provoked by lipid lowering drugs may be favored by pre-existing
      myopathy.

PMID- 9569910
TI  - [Psoas abscess complicating Crohn disease].

PMID- 9569909
TI  - [False elevated serum level of circulating calcitonin induced by omeprazole].

PMID- 9569911
TI  - [The role of prostacyclin in distal ischemia indicating cancer].

PMID- 9569912
TI  - [Treatment of malignant tracheo-bronchial tumors. The lost generation].
AB  - 250,000 new cases of endobronchial carcinoma are diagnosed each year in France.
      Risk factors are well known: 80-90% are related to smoking. With an overall 5
      year survival rate of only 10%, preventive measures must be our number one
      priority, especially for young patients, but are their parents a lost generation?
      Curative therapy has made some progress, particularly with surgery, although only
      20% of the patients are potential candidates at diagnosis, and chemotherapy,
      sometimes in combination with radiotherapy for nonoperable patients. Interesting
      results have also been achieved with gene therapy where direct intratumoral
      injection of cytokine genes on recombinant adenoviruses has provided response in
      certain cases. Interventional bronchoendoscopy provides another promising option
      as demonstrated by Jeanfaivre and Tuchais who report their results with
      electrotherapy in this issue of La Presse Medicale.

PMID- 9569913
TI  - [Therapy and prevention of the use of narcotics in Europe].

PMID- 9569915
TI  - [Benign prostatic hypertrophy. Diagnosis, complementary examination, therapeutic
      choice].

PMID- 9569914
TI  - [Synovial sarcoma. Epidemiologic and histologic data, prognostic factors and
      treatment].

PMID- 9569916
TI  - [Toxicity of ecstasy].

PMID- 9569917
TI  - [Alzheimer disease; correct the cholinergic deficit!].

PMID- 9569918
TI  - ["AIDS in Corsica"].

PMID- 9569919
TI  - [Thrombolysis in the acute phase of myocardial infarction].

PMID- 9569920
TI  - [Angioplasty in the acute phase of myocardial infarct: priority or complementary
      therapy?].

PMID- 9569921
TI  - [Role of the coronary endothelium in vasomotricity].

PMID- 9569922
TI  - [New aspects of myocardial infarct. Right ventricular infarct].

PMID- 9569923
TI  - [New aspects of myocardial infarction. New biological markers].

PMID- 9569924
TI  - [New aspects of myocardial infarct. Myocardial protection after infarct. Reality
      and controversies].

PMID- 9569925
TI  - [Effect of arterial hypertension on the myocardium. Coronary insufficiency].

PMID- 9569926
TI  - [Effect of arterial hypertension on the heart. Cardiac insufficiency].

PMID- 9569927
TI  - Prognostic classification in myelodysplastic syndromes.
AB  - Factors for predicting the prognosis of myelodysplastic syndromes (MDS) have been
      widely used over the last few years. The proportion of bone marrow blasts, number
      and severity of cytopenias, and cytogenetic abnormalities are the main prognostic
      factors and can be used in combination to determine prognostic scores capable of
      predicting the outcome with fairly high accuracy. Molecular biology parameters,
      such as RAS and p53 mutations, can also be of assistance in establishing a
      prognosis. Factors that predict responsiveness to therapy are usually the same as
      those that predict survival. Current prognostic scores are unable to identify the
      minority of patients who will have very long survivals and therefore require no
      treatment.

PMID- 9569928
TI  - [Intensive chemotherapy in myelodysplastic syndromes].
AB  - Intensive AML-like chemotherapy with anthracycline and cytosine-arabinoside or
      similar combinations gives lower CR rates and CR durations when administered to
      patients with severe MDS or AML evolving from prior MDS than to these with de
      novo AML. However such intensive therapies could be beneficial to younger
      patients without unfavorable cytogenicity when they don't have an available donor
      for allogeneic transplant. Numerous studies with high dose cytosine, arabinoside,
      idavudicine, fludarabine drugs that reverse mdr expression, or granulocytic
      growth factors have been conducted or are still ongoing in order to try to
      improve these results. In patients achieving a complete remission,
      intensification with autologous transplantation has also to be evaluated.

PMID- 9569929
TI  - [Multi-drug resistance and myelodysplastic syndromes: a possible role for
      remission inducing agents?].
AB  - Expression of P-glycoprotein (PGP), the product of the multidrug resistance gene
      (mdr1), is common in myelodysplastic syndromes (MDSs) and explains in part the
      low rate of complete remissions (CRs) obtained after aggressive chemotherapy.
      Reversion of the mdr phenotype to restore chemosensitivity has been the focus of
      many studies over the last ten years. Two phase III studies evaluated quinine for
      obtaining reversion of mdr gene expression in MDSs treated by aggressive
      chemotherapy. Results suggested better response rates and longer survival times
      in quinine-treated MDR-positive patients. However, the toxicity of quinine
      warrants further work aimed at developing other mdr phenotype reversion-inducing
      agents. Some such agents have proved superior over quinine in in vitro studies.
      Reversion of other mechanisms underlying chemoresistance in MDSs is a promising
      avenue of research.

PMID- 9569930
TI  - Allogeneic and autologous stem cell transplantation in myelodysplastic syndromes.
AB  - Allogeneic bone marrow transplantation is the only currently available curative
      treatment for myelodysplastic syndromes (MDSs) but can be used only in the
      minority of patients (10%) who are younger than 55 years or so and for whom an
      HLA-identical donor is available. Each year in Europe, about 100 patients with
      MDSs receive an autologous bone marrow transplant. This procedure is usually
      indicated as first-line treatment, except in patients without excess of blasts or
      complex cytogenetic abnormalities. In forms with excess of blasts, chemotherapy
      prior to bone marrow transplantation deserves discussion. Autologous bone marrow
      transplants or the more recent technique involving transplantation of autologous
      peripheral stem cells can be considered in patients who have achieved a complete
      remission under aggressive chemotherapy. This method has been followed by higher
      recurrence rates in patients with MDSs than in those with de novo acute
      myeloblastic leukemia, and randomized studies are under way to compare it with
      aggressive maintenance chemotherapy.

PMID- 9569931
TI  - Autologous peripheral blood progenitor cell transplantation in patients with high
      risk myelodysplastic syndromes.
AB  - Most patients with myelodysplastic syndromes (MDSs) who achieve a complete
      remission under aggressive chemotherapy develop a recurrence within 18 to 24
      months. Autologous stem cell transplantation has therefore been suggested as a
      potential means of increasing treatment efficacy. As compared with bone marrow
      stem cell autografts, peripheral stem cell autografts have a higher harvesting
      yield and a shorter duration of aplasia after reinjection. Also, the results
      reported herein suggest that polyclonal stem cells harvested after chemotherapy
      induced aplasia and growth factor therapy are capable of ensuring normal
      hematopoiesis and may provide prolonged remissions in some patients.

PMID- 9569932
TI  - Treatment with growth factors in myelodysplastic syndromes.
AB  - In myelodysplastic syndromes (MDS), pancytopenia leads to a high risk of
      infectious and hemorrhagic complications. The progression to acute myeloid
      leukemia adds to morbidity and mortality. While transfusions of red blood cells
      and platelets are still a cornerstone of the therapy, the clinical use of
      recombinant hematopoietic growth factors has enlarged the range of therapeutic
      applications in patients with MDS. It is possible to reverse neutropenia by
      administration of G-CSF (granulocyte colony stimulating factor) or GM-CSF
      (granulocyte-monocyte colony stimulating factor). In the case of a severe
      infection, therapeutic administration of G-CSF together with antibiotics might be
      justified in otherwise neutropenic MDS patients. Since especially patients with
      only slight impairment of erythropoiesis and no transfusion dependency have the
      highest response rates but need erythropoietin (EPO) the least, pharmacoeconomic
      analyses are urgently needed. Controlled randomized trials will have to ascertain
      wether combinations of EPO with G-CSF or GM-CSF are of benefit. Clinical studies
      with thrombopoietin (megakaryocyte growth and differentiation factor) have to be
      initiated to find out whether thrombocytopenia in MDS can be reversed.

PMID- 9569933
TI  - [Therapeutic strategy in myeloblastic syndromes].
AB  - The treatment of myelodysplastic syndromes (MDSs) continues to be challenging and
      difficult to standardize. This article describes a decision tree for the
      treatment of MDSs based on age, presence or absence of a potential HLA-identical
      donor, and prognostic factors including bone marrow blast proportion, severity of
      cytopenias, and karyotype.

PMID- 9569934
TI  - Capillary gas chromatography combined with atomic emission detection for the
      analysis of DDT and metabolites.
AB  - Capillary gas chromatography with atomic emission detection (GC-AED) was
      evaluated for the determination of DDT and metabolites in biological samples.
      Utilizing chlorine-selective detection at 479 nm, DDT, DDE, and DDD were
      quantified down to the 20 ng/g (fat weight) level (S/N = 10) in cod liver oil,
      while the detection, limit was 6 ng/g (S/N = 3). With splitless injection
      performed in the pressure programmed mode, DDT and related compounds were
      quantified based on a single chlorine calibration curve (universal calibration).
      The quantitative data obtained by GC-AED were in excellent accordance with
      similar results from capillary gas chromatography with electron capture detection
      (GC-ECD), while the procedure for calibration was simplified with the former
      technique.

PMID- 9569935
TI  - Toxicity of aliphatic amines: structure-activity relationship.
AB  - SARs may enable the evaluation of the toxic potential of chemicals by drawing
      conclusions from available data on structurally-related chemicals, thus reducing
      the need for further testing. The Advisory Committee on Existing Chemicals of
      Environmental Relevance (BUA) [1,2] of the German Chemical Society (Gesellschaft
      Deutscher Chemiker [GDCh]) has compiled data on the toxicity and ecological
      impact for several groups of chemicals [3, 4]. In the present review, some common
      toxicological properties for aliphatic amines were revealed after evaluation and
      comparison of the toxicity data.

PMID- 9569936
TI  - Pyrolysis-GC-MS and CuO-oxidation-HPLC in the characterization of HMMs from
      sediments and surface waters downstream of a pulp mill.
AB  - High molecular mass fractions of lignin and humic compounds in sediments and
      waters downstream of a pulp mill were characterized applying pyrolysis-gas
      chromatography-mass spectrometry. The results were compared to those obtained
      using reversed phase HPLC on the cupric oxide oxidation products. The
      chromatographic data of both pyrolysis and cupric oxide oxidation were also
      subjected to the principal component analysis (PCA). The sediment samples and
      fractions obtained by ultrafiltration of river water samples were freeze dried
      prior to characterization. The sediment samples were also extracted using 2 M
      sodium hydroxide solution. The extracts were ultrafiltrated, freeze dried and
      compared to the freeze dried original sediments using the procedures mentioned
      above. The amounts of HMMs obtained from the sediments ranged from 62 mg to 97 mg
      per one gram of sediment. Gel permeation chromatography was applied to samples
      obtained from sediments by extraction with tetrahydrofuran. The weight average
      molecular weights of these fractions were in the range of 1500-2300 amu.

PMID- 9569937
TI  - Occurrence, fate and effects of pharmaceutical substances in the environment--a
      review.
AB  - Medical substances (pharmaceuticals) are a group of substances that until
      recently have been exposed to the environment with very little attention. The
      reason why they may be interesting as environmental micropollutants, is that
      medical substances are developed with the intention of performing a biological
      effect. Especially antibiotics used as growth promoters, as feed additives in
      fish farms are anticipated to end up in the environment. Very little is known
      about the exposure routes of the medical substances to the environment. Only few
      investigations have reported findings of medical substances in other field
      samples than sediment or treated waste water samples. Several substances seem to
      be persistent in the environment. This paper outlines the different anticipated
      exposure routes to the environment, summarises the legislation on the subject and
      gives an outline of present knowledge of occurrence, fate and effect on both the
      aquatic and terrestrial environments of medical substances. Present knowledge
      does not reveal if regular therapeutic use may be the source of a substance
      carried by sewage effluent into the aquatic system, even though clofibrate, a
      lipid lowering agent, has been identified in ground and tap water samples from
      Berlin. Further research would be necessary to assess the environmental risk
      involved in exposing medical substances and metabolites to the environment.

PMID- 9569938
TI  - Generalization of independent response model for toxic mixtures.
AB  - Interaction between toxic compounds has long been known to researchers. Attempts
      to model this interaction have been based on two basic paradigms--termed
      additivity and independence (1, 2). Previous models based on these assumptions
      focused on measuring the interaction between the compounds and then classifying
      the type of interaction as synergism, antagonism, additivity or independence (3,
      4). The aim of this work is to present a generalization of the independent action
      hypothesis that is quantitatively capable of describing deviations regardless of
      the underlying single component dose response models. The mathematical framework
      of copulas is employed. This approach is then tested against data sets with both
      human health and ecological risk applications.

PMID- 9569939
TI  - The transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans from soil
      into eggs of foraging chicken.
AB  - The levels of the 2,3,7,8-chlorosubstituted PCDD/Fs (polychlorinated dibenzo-p
      dioxins and dibenzofurans) were determined in eggs of foraging chicken and in the
      corresponding soils. Compared to eggs from hens kept without soil contact the
      determined levels were clearly elevated. These increased levels were attributed
      to soil related PCDD/F uptake and were used to deduce congener specific factors
      describing the transfer from soil into the eggs by the foraging. Based on these
      transfer factors an calculation method allowing the prediction of the 2,3,7,8
      TCDD toxic equivalent (I-TEq) levels in eggs based on the PCDD/F concentrations
      in soil was developed. The comparison of predicted and determined PCDD/F levels
      was used to discuss limitations and uncertainties of the model. Based on a given
      soil contamination, this approach allows a conservative prediction of the I-Teq
      levels in eggs of foraging chicken.

PMID- 9569941
TI  - Microcystin LR degradation by Pseudomonas aeruginosa alkaline protease.
AB  - We isolated several species of bacteria from the surface water of a Japanese
      lake. Of the isolated bacteria, Pseudomonas aeruginosa was the only species which
      could degrade microcystin LR in vitro. Microcystin LR decreased to 4.5% of the
      spiked microcystin LR quantity in the P. aeruginosa culture, and was metabolized
      to (2S, 3S, 8S)-3-amino-2, 6, 8-trimethyl-10-phenyldeca-4E, 6E-dienoic acid
      (DmADDA). It was possible that P. aeruginosa hydrolysed nucleophilically the
      peptide bond of microcystin LR. We examined if pyochelin, pyocyanin and alkaline
      protease produced by P. aeruginosa affected the reduction of microcystin LR. In
      the result, DmADDA was produced from microcystin LR in the presence of 100 microM
      H2O2 and 100 microM each of pyochelin, pyocyanin or both. However, the production
      of DmADDA was slight (2 to 12 mole%). After treatment with P. aeruginosa alkaline
      protease, DmADDA was produced 75 mole% from microcystin LR. Therefore, we
      concluded that microcystin was degraded mainly by the action of P. aeruginosa
      alkaline protease.

PMID- 9569940
TI  - Effect of 2,4,4'-trichloro-2'-hydroxydiphenyl ether on cytochrome P450 enzymes in
      the rat liver.
AB  - We examined the effect of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan
      DP300) on microsomal cytochrome P450 (P450) enzymes in rat liver. Rats were
      treated intraperitoneally with Irgasan DP300 daily for 4 days, at doses of 0.2,
      0.4 and 0.8 mmol/kg. Among the P450-dependent monooxygenase activities, 7
      benzyloxyresorufin O-debenzylase (BROD) and 7-pentoxyresorufin O-depentylase
      (PROD) in rats, which are associated with CYP2B1, were remarkably induced by all
      doses of Irgasan DP300. The relative induction to each control activity were from
      5.6- to 22.3-fold and 4.9- to 20.2-fold, respectively. Furthermore,
      immunoblotting showed that CYP2B1/2 protein level in rat liver microsomes was
      increased from 10.8- to 34.4-fold by Irgasan DP300. In addition, 7-ethoxycoumarin
      O-deethylase (ECOD) and p-nitrophenol hydroxylase (PNPH) activities were
      significantly increased by Irgasan DP300 at all doses (from 1.4- to 4.9-fold).
      Although the activities of other P450-dependent monooxygenases, namely
      aminopyrine N-demethylase (APND), aniline p-hydroxylase (ANPH), erythromycin N
      demethylase (EMND), lauric acid omega-hydroxylase (LAOH) and testosterone 6 beta
      hydroxylase (TS6BH) were increased at high doses (> or = 0.4 mmol/kg) of Irgasan
      DP300, the relative level was lower than those of the CYP2B1-dependent
      monooxygenases such as BROD and PROD. However, 7-ethoxyresorufin O-deethylase
      (EROD), 7-methoxyresorufin O-demethylase (MROD), testosterone 2 alpha-hydroxylase
      (TS2AH) and testosterone 7 alpha-hydroxylase (TS7AH) activities were not affected
      by any doses of Irgsan DP300. Immunoblotting showed that CYP3A2/1 and CYP4A1
      protein levels were significantly induced from 1.3- to 2.2-fold by Irgasan DP300
      (> or = 0.4 mmol/kg), whereas those of CYP1A1/2, CYP2C11/6 and CYP2E1 were not
      affected by any doses of Irgasan DP300. These results suggest that Irgasan DP300
      induces the P450 isoforms of CYP2B subfamily in the rat liver, and that the
      induced P450 isozymes closely relates to the toxicity of Irgasan DP300 or its
      chlorinated derivatives.

PMID- 9569942
TI  - Fingerprint of polycyclic aromatic hydrocarbons in two populations of southern
      sea lions (Otaria flavescens).
AB  - The fingerprint of 14 polycyclic aromatic hydrocarbons (PAHs) was investigated in
      biopsy, fur, blood, liver and faeces of live and dead specimens of two
      Argentinian population of southern sea lion (Otaria flavescens). One colony lives
      in Mar del Plata harbour which is particularly polluted with petroleum, the
      second (control) colony lives at Punta Bermeja (Patagonia). The highest
      concentrations of the five carcinogenic PAHs were found in the Mar del Plata sea
      lions.

PMID- 9569943
TI  - Apparent first-order kinetics in the transformation of 1,1,1-trichloroethane in
      groundwater following a transient release.
AB  - A transient release of 1,1,1-trichloroethane (TCA) to an otherwise uncontaminated
      aquifer at a manufacturing facility presented a useful opportunity to validate
      the results of previous laboratory and field studies on TCA transformation in
      groundwater. Abiotic TCA transformation to 1,1-dichloroethylene (DCE) and acetic
      acid at the site exhibited first-order kinetics with half-life of 2.9 years 15
      degrees C. Degradation effects were seen to overwhelm chemical retardation
      effects on the DCE/TCA concentration ratio in groundwater. The kinetic data was
      sufficient to date the release to within one week of when it actually occurred. A
      kinetic approach may be applicable to dating the releases on other contaminated
      sites where a single transient release is indicated. The transformation of
      dissolved TCA in groundwater with a half-life of several years can be expected at
      many contaminated sites.

PMID- 9569944
TI  - Geographical distribution and background levels of total mercury in air in Japan
      and neighbouring countries.
AB  - Concentrations of total atmospheric mercury were determined in air collected from
      several locations in Japan and neighbouring countries to elucidate the
      geographical distribution and the background levels of total mercury in
      environmental air. The concentrations of mercury in urban air in Japan were 2.3
      67 ng/m3, mean value 11.2 ng/m3. Those values were higher relative to those in
      urban air of other countries around Japan. In the past, a large quantity of
      mercury was used as an agricultural fungicide and a chloralkali catalyst in
      Japan. Therefore, the concentrations of mercury in rural air were higher rather
      than those in urban air. This phenomenon supports the hypothesis that the
      residual mercury used in the paddy field in the 1970s still remains in soils of
      Japan.

PMID- 9569945
TI  - Biodegradation and aquatic toxicity of beta-alaninediacetic acid (beta-ADA).
AB  - The aquatic toxicity and biodegradability of the new chelating agent beta
      alaninediacetic acid (beta-ADA) were investigated. There is no inhibition effect
      of beta-ADA in the daphnia magna 24 h test up to a concentration of 1000 mg/L.
      The algal growth inhibition test resulted in an EC 50 of 19.7 mg/L. An EC 20 of
      740 mg/L was determined in the luminescent bacteria test. An EC 50 was not
      obtained in this test up to a concentration of 2000 mg/L beta-ADA. The degree of
      biodegradation of beta-ADA was determined in a static and a continuous test. The
      beta-ADA removal reached 98% at the end of the test after eight weeks in the
      continuous test which was carried out with laboratory activated sludge units
      simulating a waste water treatment plant. Further, biodegradation and toxicity
      tests were coupled, i.e. the effluents of the laboratory activated sludge units
      were applied in the toxicity tests. A higher toxicity of the effluents of the
      test units in comparison with the control unit was not observed.

PMID- 9569947
TI  - Effect of toxaphene on reproduction of fish.
AB  - The effect of Toxaphene on fish reproduction was investigated in sexually mature
      female zebrafish fed for two weeks with food contaminated with three different
      concentrations of the Pesticide (0.02, 0.23 and 2.2 micrograms/g fish/day). No
      overt differences were observed in reproductive success as assessed by
      examination of (a) total number of eggs spawned by each female, (b) percentage of
      fertilized eggs 24 hours after fertilization, (c) percentage of embryo mortality
      72 hours after fertilization and (d) percentage of hatching 72 hours after
      fertilization. By contrast Toxaphene produced distinct effects of a dose response
      nature on oviposition. This observation is not only of interest with respect to
      Toxaphene, but also points to the importance of evaluating other pesticides for
      their effect on the oviposition of feral species that might be even more
      sensitive than zebrafish. Toxicity of Toxaphene was manifested both in the parent
      fish (skin discoloration, subcutaneous hemorrhages, particularly around the gill
      areas and backbones curved in the vertical plane) and in hatching embryos (half
      hatched).

PMID- 9569946
TI  - Review of the estrogenic and antiestrogenic activity of polycyclic aromatic
      hydrocarbons: relationship to carcinogenicity.
AB  - Human exposure to nonsteroidal estrogens in the environment has recently been
      proposed as a risk factor for endocrine disruption and the development of cancers
      of the breast and reproductive tract. Certain polycyclic aromatic hydrocarbons
      (PAHs), which closely resemble steroid hormones, are ubiquitous environmental
      contaminants whose carcinogenicity has been extensively studied. This review
      examines the available evidence regarding the actions of PAHs on estrogen
      receptor activity, estrogen metabolism and the hypothalamo-pituitary axis. In
      most studies, PAHs exhibited either weakly estrogenic or antiestrogenic
      responses. The possibility is raised that the endocrine toxicology of certain
      PAHs reflects both genotoxic and non-genotoxic components which may be
      interrelated, particularly with regard to carcinogenesis.

PMID- 9569948
TI  - Cancer in end-stage renal disease: potential factors involved -editorial-.
AB  - Increased incidence of cancer at various sites is observed in patients with end
      stage renal disease (ESRD). In particular, lymphomas and carcinomas of the
      kidney, prostate, liver and uterus show an enhanced prevalence in these subjects
      compared with the general population. A multitude of factors directly or
      indirectly associated with the renal disease and the treatment regimens may
      contribute to the increased tumor formation in these patients. Impaired function
      of the immune system and of DNA repair mechanisms as well as reduced antioxidant
      defense, accumulation of carcinogenic compounds partly due to reduced renal
      elimination as well as chronic infections and inflammations are found more
      frequently in patients with ESRD compared with the general population and may act
      in concert to accelerate malignant transformation and tumor formation.

PMID- 9569949
TI  - Effects of age and diabetes on blood flow rate and primary outcome of newly
      created hemodialysis arteriovenous fistulas.
AB  - To study the feasibility of creating a radiocephalic hemodialysis fistula in
      elderly and diabetic patients, we prospectively studied 176 patients undergoing
      the first permanent vascular access creation and followed the outcome of fistula
      until primary failure or success was assessed. Color duplex ultrasonography was
      used to measure the blood flow rate. Fistula blood flow rate was significantly
      smaller in elderly patients, however, it was > 400 ml/min in over 78% of the
      elderly patients with successful fistulas. There was no difference in fistula
      blood flow rate between nondiabetics and diabetics. Dialysis adequacy (Kt/V) via
      fistula was the same between age groups and between diabetes mellitus status. Old
      age or diabetes per se did not significantly predispose a new fistula to primary
      failure, but concurrent old age and diabetes markedly increase the risk. In
      conclusion, a good primary outcome of newly created radiocephalic fistula and
      adequate dialysis via fistula were demonstrated for elderly and diabetic
      patients. However, the longevity of fistula in elderly and diabetic patients
      needs further study.

PMID- 9569950
TI  - Effect of Ramadan fasting on Moslem kidney transplant recipients.
AB  - This study was carried out to find out whether Ramadan fasting would affect the
      renal function in kidney transplant recipients with normal or impaired graft
      function. Twenty-three transplant recipients, 17 with a normal function and 6
      with an impaired but stable function with plasma creatinine levels not exceeding
      300 mmol/l, were included in this study. The mean posttransplant period was 2.0
      (range 0.6-6.3) years. Urinary and serum biochemical parameters, ciclosporin A
      level, and hematocrit were checked weekly, during Ramadan as well as 1 week
      before and after. Statistical analysis showed no significant changes in all
      parameters before, during, and after Ramadan. In conclusion, our findings
      indicate that fasting during the month of Ramadan does not seem to be associated
      with any significant adverse effects in kidney transplant recipients with normal
      or impaired graft function and suggest that it is safe for those patients to fast
      during Ramadan after 1 year of renal transplantation.

PMID- 9569951
TI  - Remarkable removal of beta-2-microglobulin by on-line hemodiafiltration.
AB  - Eight chronic, anuric hemodialysis patients were randomly treated with a high
      flux polysulphone dialyzer (F80), using 6 different modes: conventional
      bicarbonate hemodialysis (HD), hemodiafiltration (HDF) with a replacement
      solution at 40, 60, 80 or 100 ml/min in postdilution and 80 ml/min in
      predilution. The differences in beta 2-microglobulin (beta 2M) reduction ratio
      and clearance were evaluated statistically by analysis of variance (ANOVA). Both
      studies revealed no significant difference between HD and HDF40 in postdilution,
      but an increasing significant difference from HDF60 to HDF100 in postdilution and
      with HDF80 in predilution. The mean reduction ratio ranged from 49.7 (HD) to
      72.7% (HDF 100 ml/min), showing an overall statistically significant difference
      (p = 0.0000). For the clearance, the range was between 63.8 (HD) and 116.8 ml/min
      (HDF 100 ml/min) (p = 0.0000). beta 2M in the effluent dialysate with HDF 100
      ml/min reached up to a mean of 258 mg/session. Concerning small molecules (BUN,
      creatinine and P), there was a statistically significant different clearance for
      creatinine and especially for P with HDF 100 ml/min. CONCLUSION: HDF with an on
      line replacement solution at 100 ml/min and a high-flux and biocompatible
      polysulphone membrane represents a new tool for enhanced removal of beta 2M.
      Besides a significant increase in creatinine and especially in phosphorus
      clearance is noted.

PMID- 9569952
TI  - Predictive value of functional status for mortality in patients on maintenance
      hemodialysis.
AB  - In patients receiving maintenance hemodialysis, laboratory indices (such as serum
      albumin concentration) are predominantly utilized to assess well-being, while
      measures of functional status are rarely applied. However, the serum albumin
      concentration declines with advancing age, and the mean age of patients starting
      maintenance hemodialysis is now over 63 years. Using a 14-level modified
      Karnofsky activity scale, we measured baseline functional status in 522 randomly
      selected hemodialysis patients and prospectively monitored them for 3 years to
      determine the predictive value of our modified Karnofsky score for mortality. At
      onset of study, serum albumin and creatinine concentrations as well as hematocrit
      were measured and the comorbid conditions documented. At baseline, the 522
      subjects (270 women and 252 men) included 327 blacks (63%), 154 whites (29%), 31
      Hispanics (6%), and 10 Asians (2%) of mean age 59 +/- (SD) 15 years. The mean
      duration of end-stage renal disease was 4 +/- 3.6 years, and the mean serum
      albumin concentration was 3.7 +/- 0.4 g/dl. 166 (32%) of the patients died during
      the observation period. Cox regression analysis revealed inverse relations
      between mortality and both our modified Karnofsky score (p = 0.0001) and serum
      albumin concentration (p = 0.001). The predictive value of a low modified
      Karnofsky score for mortality persisted after analysis of subjects stratified
      according to serum albumin concentration (< 4 g/dl, n = 382, p = 0.0001 vs. > or
      = 4 g/dl, n = 140, p = 0.008). With a modified Karnofsky score (< 70 vs. > or =
      70), the relative risk of death during the 3-year follow-up period was 1.44 (95%
      confidence interval 1.236, 1.675; p < 0.0001). Forward stepwise Cox regression
      analysis showed that advanced age (p = 0.0005), white race (p = 0.0009), diabetes
      mellitus (p = 0.01), and a low serum albumin concentration (p = 0.003) were
      independently associated with an increased risk of mortality during follow-up
      after adjustment for other factors. A modified Karnofsky score (p = 0.14) did not
      predict survival in the Cox model when other independent variables were included.
      We conclude that in patients with end-stage renal disease sustained on
      maintenance hemodialysis, a poor functional status (measured on a modified
      Karnofsky activity scale) is associated with early mortality. Periodic
      measurement of modified Karnofsky score is a simple, low-cost, and reliable means
      of identifying patients on dialysis at risk for early death.

PMID- 9569953
TI  - Spiral computed tomographic angiography--a new technique for evaluation of
      vascular access in hemodialysis patients.
AB  - Spiral computed tomographic angiography (CTA), a new noninvasive imaging
      technique, was used to study 10 arteriovenous fistulas (AVF) in 9 hemodialysis
      patients. Digital subtraction angiography (DSA) was also performed as a gold
      standard for comparison. AVF stenosis was graded by a four-point scale: grade 0,
      well patency of supplying artery, anastomosis and drainage vein; grade 1, < 50%
      stenosis; grade 2, 50-70% stenosis; grade 3, 70-99% stenosis, and grade 4, total
      occlusion. We found CTA correlated closely to DSA in detecting both stenosis and
      dilatation of AVF and it spared all the shortcomings of DSA. CTA has the
      potential to be alternative for imaging of dialysis fistulas. Further studies
      will be performed to specify the role of CTA images in the assessment of the
      hemodialysis vascular access.

PMID- 9569954
TI  - Evaluation of renal tubular functions in convalescent phase of hemorrhagic fever
      with renal syndrome.
AB  - To evaluate renal tubular functions and to investigate the causative factors of
      urinary-concentrating defects in the late stage of hemorrhagic fever with renal
      syndrome (HFRS), 11 HFRS patients in the convalescent phase were studied and
      compared with 8 acute renal failure (ARF) patients in convalescence (disease
      controls) and 9 healthy adults preparing for kidney donation (normal controls,
      NC). Minimal urine osmolality induced by water loading was higher (p < 0.05) in
      HFRS (89.5 +/- 22.1 mosm/kg) and ARF patients (84.8 +/- 14.7 mosm/ kg) than in NC
      (47.8 +/- 4.6 mosm/kg), but the solute-free water clearance of HFRS patients (9.0
      +/- 1.3%), measured at maximal diuresis, was not different from that of ARF
      patients (6.7 +/- 1.2%) or NC (10.5 +/- 1.4%). After 12-hour water deprivation +
      vasopressin stimulation, HFRS had lower urine osmolality (433.7 +/- 31.1 versus
      850.0 +/- 35.1 mosm/kg; p < 0.05), urine-to-plasma osmolality ratio (1.47 +/-
      0.11 versus 2.91 +/- 0.11; p < 0.05), and solute-free water reabsorption (0.53 +/
      0.07 versus 0.91 +/- 0.12%; p < 0.05) than NC. As compared with ARF patients
      (1.09 +/- 0.16%) or NC (1.49 +/- 0.16%), HFRS patients (0.43 +/- 0.20%) had lower
      solute-free water reabsorption measured at maximal antidiuresis induced by water
      deprivation + vasopressin stimulation + hypertonic saline infusion (p < 0.05). In
      HFRS, the plasma vasopressin level and plasma vasopressin/osmolality ratio
      increased from 3.9 +/- 0.8 to 6.1 +/- 1.1 pg/ml and from 0.013 +/- 0.003 to 0.020
      +/- 0.004 pg/ml/mosm/kg after 12-hour water deprivation, respectively (p < 0.01).
      However, neither basal nor stimulated values of the plasma vasopressin level or
      plasma vasopressin/osmolality ratio was different among the 3 groups. HFRS
      patients were not different from ARF patients or NC in lithium clearance, urinary
      acidifying capacity, and fractional excretions of sodium, potassium and
      bicarbonate. We conclude that in the convalescent phase of HFRS, the urinary
      acidifying ability is not disturbed, the urinary-diluting defect is mild, and the
      urinary-concentrating capacity is obviously impaired. This study suggests that
      the most important factor contributing to the urinary-concentrating defect in
      HFRS is the reduced collecting duct responsiveness to vasopressin.

PMID- 9569955
TI  - End-stage renal interstitial fibrosis in an adult ten years after ifosfamide
      therapy.
AB  - A 33-year-old male presented with end-stage renal failure. Renal biopsy showed
      severe interstitial fibrosis without glomerulopathy or vasculopathy. More than 10
      years previously the patient had been successfully treated for recurrent
      rhabdomyosarcoma. The treatment included ifosfamide, a drug known to cause acute
      tubular dysfunction. Though a possible synergistic effect of previous radiation
      which was well within accepted tolerance limits cannot be excluded, it would
      appear that ifosfamide was almost certainly the major cause of the late onset
      chronic renal disease.

PMID- 9569956
TI  - Collagenofibrotic glomerulonephropathy associated with immune complex deposits.
AB  - A 66-year-old Japanese male, who suffered from persistent proteinuria and leg
      edema, underwent renal biopsy. Light microscopy revealed marked narrowing of the
      glomerular capillary lumen with a diffuse accumulation of weakly PAS-positive
      material. By electron microscopy, abundant abnormal collagen fibers were observed
      predominantly in the subendothelial space and occasionally in the mesangial
      matrix. The fibers had a periodicity of about 60 nm and were immunoreactive for
      anti-type III collagen. Subendothelial electron-dense deposits were also found in
      some of the capillary walls. The serum level of procollagen III peptides was
      elevated and changed in parallel with the amount of proteinuria during the
      patient's clinical course. On the basis of these findings, a diagnosis of the
      collagenofibrotic glomerulonephropathy was made. A review of the literature,
      including 29 similar or identical cases, failed to reveal the etiology and
      pathogenesis of this disease. We suggest that this disease may be divided into
      two different clinical subtypes, an adult-onset type and a pediatric type.

PMID- 9569957
TI  - Intraventricular and brachial artery thrombosis in nephrotic syndrome.
AB  - A 23-year-old Saudi female presented with nephrotic syndrome. On renal biopsy she
      had primary focal and segmental glomerulosclerosis which was resistant to
      steroids. Two years later she presented with absent left arm pulses and on
      investigation a diagnosis of left ventricular thrombosis and thromboembolism of
      left brachial artery was made. Low antithrombin III, high fibrinogen levels and
      diuretic therapy were the possible causative factors for hypercoagulable state.
      On anticoagulation therapy initiated with heparin and continued with warfarin for
      8 weeks there was complete dissolution of intraventricular and improvement of
      left brachial artery thrombosis. An early diagnosis and treatment of this
      potentially serious complication of nephrotic syndrome are stressed.

PMID- 9569958
TI  - Recurrent crescentic membranous nephropathy in two successive renal transplants:
      association with choroidal effusions and retinal detachment.
AB  - We report the case of a 50-year-old man in whom crescentic membranous nephropathy
      recurred in two successive renal transplants leading rapidly to renal failure.
      Deterioration of renal function was associated with choroidal effusions and
      retinal detachments. Multiple serologic tests were negative. High-dose steroids,
      cyclophosphamide, cyclosporine, plasmapheresis and OKT3 failed to arrest the
      deterioration of renal function.

PMID- 9569959
TI  - A case of Guillain-Barre syndrome developed minimal change nephrotic syndrome
      simultaneously.
AB  - A case who developed Guillain-Barre syndrome (GBS) and nephrotic syndrome (NS)
      simultaneously is reported. In this case, the onset of nephrotic change of
      proteinuria coincided with the development of the neurological disturbance.
      Analysis of renal biopsy by light, immunofluorescent and electron microscopy
      showed minor glomerular abnormalities. The occurrence of GBS in association with
      NS is rare, and moreover most cases in the previous reports had membranous
      nephropathy. Only 1 case had minimal change nephrotic syndrome (MCNS). To our
      knowledge, this is the first report of a case beneficially treated with
      glucocorticoids, suggesting that immune disorder may play an important role in
      the association between MCNS and GBS.

PMID- 9569960
TI  - A patient with thrombotic microangiopathy accompanied by glomerular
      subendothelial electron dense deposits.
AB  - A 50-year-old woman presented with thrombocytopenia, microangiopathic hemolytic
      anemia, and nephrotic syndrome. Although a high level of circulating immune
      complexes, mild hypocomplementemia, and the antinuclear antibody also were
      present, the criteria for collagen disease were not fulfilled. Renal biopsy
      demonstrated a typical thrombotic microangiopathy (TMA) involving glomeruli.
      There also were electron-dense deposits located just beneath the original
      glomerular basement membrane in the dilated subendothelial space, thought to be
      immune complexes following positive IgG, C1q and C3 staining on an
      immunofluorescent study. Corticosteroid therapy rapidly ameliorated her
      hematologic abnormalities and proteinuria and normalized the immunologic data.
      These findings strongly suggest that the TMA in this patient was induced by
      immune complex-associated mechanisms.

PMID- 9569961
TI  - Renal oncocytoma of the native kidney after renal transplantation.
AB  - Patients with acquired cystic kidney disease (ACKD) are at an increased risk of
      renal neoplasms. Frequent tumors are adenomas and renal cell carcinomas. However,
      renal oncocytomas may occur in patients with ACKD. Little is known about
      oncocytomas of the native kidney following renal transplantation. By means of B
      scan ultrasonography, a solid and echo-inhomogeneous renal mass was
      incidentically observed in the right native kidney of a 28-year-old female
      patient with ACKD 4 years following renal transplantation. A nephrectomy was
      performed. The histological examination revealed a renal oncocytoma. The
      increased prevalence of neoplasms in the case of ACKD and following renal
      transplantation requires careful monitoring of the patients concerned. In very
      rare cases a renal oncocytoma may develop in the native kidney after renal
      transplantation.

PMID- 9569963
TI  - Visceral leishmaniasis in a renal transplant recipient. Short review and therapy
      alternative.

PMID- 9569962
TI  - Eicosapentaenoic acid inhibits mitogen-induced endothelin-1 production and DNA
      synthesis in cultured bovine mesangial cells.
AB  - The present study was designed to examine whether eicosapentaenoic acid (EPA)
      inhibits the production of basal or stimulated endothelin (ET)-1 by platelet
      derived growth factor (PDGF)-BB or epidermal growth factor (EGF), and DNA
      synthesis in cultured bovine mesangial cells. PDGF-BB and EGF stimulated ET-1
      secretion in a dose-dependent fashion in these cells. EPA (10-100 microM)
      exhibited dose-related inhibition of PDGF-BB- and EGF-stimulated ET-1 secretion.
      EPA had no inhibitory effects on basal ET-1 secretion in these cells. Moreover,
      50 microM EPA significantly attenuated PDGF-BB- and EGF-stimulated [3H]thymidine
      incorporation into mesangial cells. Receptor-binding experiments showed that EPA
      competitively inhibited 125I-PDGF-BB or 125I-EGF binding to mesangial cell
      surface receptors. Scatchard analysis for PDGF-BB receptor or EGF receptor
      revealed a linear regression fit and one binding site. Pretreatment with 50
      microM EPA suppressed the number of maximum binding sites, but did not affect the
      Kd values. These results indicate that EPA potentially inhibits mesangial cell ET
      1 production, when stimulated by PDGF-BB or EGF. This inhibitory effect of EPA
      could be related to the attenuation of mesangial cell proliferation via
      inhibition of the binding of PDGF-BB or EGF to their receptors due to alteration
      of the physicochemical characteristics of the cell membrane.

PMID- 9569964
TI  - Preparation of a phosphorus-enriched hemodialysate using an 'acid concentrate'
      solution and a sodium bicarbonate powder.

PMID- 9569966
TI  - Reproducibility and efficiency testing of two sampling methods for image analysis
      in cytology.
AB  - OBJECTIVE: Quantitative nuclear DNA analyses and nuclear morphometry have become
      a widely used tool in pathology. Nevertheless, studies done by different
      observers utilizing the same methods very often have shown different results. One
      of the reasons could be that different sampling methods were used. In this study
      two selection methods for image analyses (the consecutive selection method and
      the random selection method) were tested for reproducibility and efficiency.
      STUDY DESIGN: Using an interactive imaging analysis system, 10 cases (5 breast
      adenocarcinomas, 3 prostatic cancers, 1 sarcoma, 2 prostatic hyperplasias) were
      measured twice by using each sampling method. Median nuclear area and entropy
      (i.e., a statistical descriptor of DNA histograms) were the parameters
      calculated. RESULTS: The results showed that using the consecutive selection
      method, the number of individual nuclei in a cytologic sample that should be
      measured to obtain reproducible results was 150 for nuclear area and 110 for
      entropy. The corresponding figures using random systematic selection method were
      80 for assessment of nuclear area and 100 for assessment of entropy. CONCLUSION:
      Both methods showed high reproducibility and a good correlation with each other.
      The mathematical idea of "plateau values," which was used to estimate the number
      of measurements needed, was considered a good contribution to increasing the
      efficiency of both methods.

PMID- 9569965
TI  - Accuracy of nuclear classification in cervical smear images. Quantitative impact
      of computational deconvolution and 3-D feature computation.
AB  - OBJECTIVE: To investigate the accuracy with which the nuclei of cells in
      overlapped and thick clusters in cervical/ vaginal smears can be classified
      independent of the segmentation algorithm used and to determine the influence of
      three-dimensional (3-D) processing as compared to two-dimensional (2-D) methods
      on classification of the nuclei. STUDY DESIGN: Cell clusters were imaged from 31
      ThinPrep smears composed of 808 nuclei, of which 420 were determined to be
      abnormal by a cytotechnologist. Sets of 2-D and 3-D volumetric features of the
      detected nuclei were formulated, and classifiers were constructed. The effect of
      computational deconvolution on classification was assessed using nearest-neighbor
      and Wiener filter in 2-D and 3-D before calculating features. A "best focus
      plane" was calculated for each nucleus from the 3-D data set, and the 2-D
      features in this plane were also analyzed.

PMID- 9569967
TI  - Atomic force microscopy in effusion cytology.
AB  - OBJECTIVE: To investigate whether atomic force microscopy (AFM) in combination
      with classical light microscopy allows simple identification of surface
      structures of cells from pleural and ascitic fluids for diagnostic purposes in
      place of scanning electron microscopy (SEM). STUDY DESIGN: We examined a total of
      180 cells obtained from 9 reactive pleural or peritoneal effusions, 14 associated
      with carcinomatosis from histologically confirmed tumors and 5 from
      mesotheliomas. Cells of interest were selected in air-dried, uncovered, May
      Grunwald-Giemsa (MGG)-stained smears and subsequently investigated by AFM.
      Incorporation of a very compact AFM scanner into the nose piece of a conventional
      Axioscope light microscope allowed alternating application of both techniques.
      RESULTS: AFM was able to detect cell surface structures, such as microvilli,
      phagocytic pits, secretory blebs and lytic holes. The image resolution was
      sufficient but not as good as that with SEM. We found differences in number,
      length and diameter of microvilli between cells from mesotheliomas and from
      metastatic adenocarcinomas. CONCLUSION: As AFM can be carried out in combination
      with light microscopy quickly and easily on uncovered, MGG-stained smears, we
      propose this method as a suitable tool for obtaining additional useful
      information in routine cytologic diagnosis of effusions.

PMID- 9569968
TI  - Advances in high-speed, three-dimensional imaging and automated segmentation
      algorithms for thick and overlapped clusters in cytologic preparations.
      Application to cervical smears.
AB  - OBJECTIVE: To use three-dimensional (3-D) imaging and localized adaptive image
      analysis to enable automated cervical smear screening systems to efficiently and
      effectively process thick and overlapped cell clusters currently left
      unprocessed. STUDY DESIGN: Instrumentation was developed to perform high-speed
      (50-200 optical sections per second at 256 x 256 resolution), 3-D imaging of
      thick regions of cervical smears. Normal and abnormal ThinPrep smears were imaged
      at two levels of resolution to approximate higher-resolution, wide-area imaging.
      Improved dual-resolution, 3-D image analysis algorithms were developed for
      segmenting nuclei in these clusters. RESULTS: Despite low contrast, high
      variability and dense overlaps, the algorithms detected 89% and correctly
      segmented 76% of nuclei in clusters from normal smears and detected 75% and
      correctly segmented 45% of nuclei in clusters from abnormal smears in low
      resolution images. In high-resolution images they detected 88% and segmented 76%
      of nuclei from normal specimens and detected 55% and segmented 45% of nuclei from
      abnormal specimens. At least one nucleus from each cell cluster was correctly
      segmented. CONCLUSION: Selective application of 3-D imaging and 3-D image
      analysis to thick and overlapped regions can enable a significant fraction (45
      89%) of clustered and embedded cells to be accessed by an automated analysis
      system. These regions are, for the most part, unprocessable by current two
      dimensional methods.

PMID- 9569969
TI  - Assessing estrogen and progesterone receptor status in fine needle aspirates from
      breast carcinomas. Results on six years of material and correlation with
      biochemical assay.
AB  - OBJECTIVE: To evaluate the usefulness of immunocytochemical staining on breast
      fine needle aspiration (FNA) cytology as a routine procedure for determination of
      estrogen (ER) and progesterone (PR) receptor status. STUDY DESIGN: FNA cytology
      material from 864 patients was immunostained for ER and PR using Abbott ER/PR-ICA
      kits. Percentage of stained nuclei, staining intensity and staining pattern was
      evaluated. In 259 cases comparison with biochemical assay was possible. RESULTS:
      Of the cases, 75.6% were ER positive and 65% PR positive, and 61.6% were both ER
      and PR positive. Approximately 4% of the smears were inconclusive because of
      scant cellularity. Concordance between the immunostaining and biochemical method
      was 84% for ER and 71% for PR. Kappa values were 0.61 and 0.4, respectively.
      Major discrepancies were found in 7.7% of the specimens. CONCLUSION: Inconclusive
      smears due to scant cellularity is a minor problem. Technical difficulties are
      few, and false negative and positive staining is rarely seen. The results are
      comparable to those from the biochemical method, and immunostaining of ER/PR on
      breast cancer FNA cytology smears is useful as a routine procedure for receptor
      determination.

PMID- 9569970
TI  - Microscope remote control with an Internet browser.
AB  - OBJECTIVE: To develop a telemicroscopy system that is independent of specialized
      hardware and software for microscope remote control. DESCRIPTION OF THE SYSTEM:
      An automatic microscope mounted on a CCD camera was connected to a computer that
      fulfills the function of an internet server. Any internet user can access this
      server and can control the microscope by use of an internet browser with Java
      support. The system can be tested at http:@amba.rz.charite.hu-berlin.de/telemic.
      FUNCTION AND APPLICATIONS: The user can move the microscope stage, change the
      magnification or execute any other microscope operations by pressing buttons of
      the downloaded telemicroscopy client program. The new microscope images are
      transferred automatically. Structures of interest within the images can be
      highlighted and discussed online with other telemicroscopy clients. Any internet
      browser with Java support, like Netscape or Microsoft Internet Explorer, makes an
      internet user a telemicroscopy client and thus a possible consultant for
      telepathology. CONCLUSION: The internet telemicroscope offers new possibilities
      for telepathology. This development should promote communication between
      pathologists and may thus increase the quality of diagnosis.

PMID- 9569971
TI  - Direct relationship between hormone sensitivity level and growth pattern.
      Evidence in 18 gastrointestinal neoplastic cell lines.
AB  - OBJECTIVE: We investigated whether a relationship exists in terms of growth
      pattern and hormone sensitivity in 18 gastrointestinal neoplastic cell lines.
      Hormones studied included gastrin, epidermal growth factor, estradiol and
      luteinizing hormone-releasing hormone. STUDY DESIGN: The growth patterns were
      assessed by means of computer-assisted microscope analysis of Feulgen-stained
      nuclei combined with the mathematical Delaunay triangulation and Voronoi paving
      techniques. This methodology enabled four variables characterizing the cell
      colony patterns to be computed. The information contributed by these variables
      was analyzed by means of discriminant analysis and the decision tree technique.
      RESULTS: Each phenotype (sensitivity level) exhibited distinct growth pattern (or
      cell colony) characteristics in the case of each hormone and/or growth factor
      under study. Furthermore, the sensitivity of the gastrointestinal cell lines to a
      given hormone (or growth factor) appeared to be peculiar to the hormone (or
      growth factor). CONCLUSION: A direct relationship seems to exist between growth
      pattern and hormone sensitivity levels in gastrointestinal cancers, particularly
      colorectal.

PMID- 9569972
TI  - Proliferative index obtained by DNA image cytometry. Does it add prognostic
      information in Auer IV breast cancer?
AB  - OBJECTIVE: To investigate whether the S + G2/M fraction (proliferative index) is
      a prognostic determinant in breast cancers classified as Auer IV. STUDY DESIGN:
      Prognostic evaluation of Auer IV DNA histograms with respect to the high versus
      low S + G2/M fraction, obtained by image cytometry on consecutive breast cancer
      imprint preparations. RESULTS: When studying recurrence-free survival (n = 136),
      the prognostic value of S + G2/M was found to vary with time: it was negligible
      before the median time to relapse (1.5 years) but thereafter statistically
      significant, in both univariate and multivariate analysis. The same pattern was
      found when overall survival was used as the end point; the effect was delayed to
      about the median time until death (three years). Tumors with a low S + G2/M
      fraction were smaller and more often estrogen receptor- and progesterone receptor
      positive than those with a high S + G2/M fraction. CONCLUSION: According to ICM
      DNA values corresponding to the S + G2/M region, patients with breast cancers
      classified as Auer IV can be divided into subgroups with different tumor
      characteristics and prognoses.

PMID- 9569973
TI  - Siberian population of the New Stone Age: mtDNA haplotype diversity in the
      ancient population from the Ust'-Ida I burial ground, dated 4020-3210 BC by 14C.
AB  - On the basis of analysis of mtDNA from skeletal remains, dated by 14C 4020-3210
      BC, from the Ust'-Ida I Neolithic burial ground in Cis-Baikal area of Siberia, we
      obtained genetic characteristics of the ancient Mongoloid population. Using the 7
      restriction enzymes for the analysis of site's polymorphism in 16,106-16,545
      region of mtDNA, we studied the structure of the most frequent DNA haplotypes,
      and estimated the intrapopulational nucleotide diversity of the Neolithic
      population. Comparison of the Neolithic and modern indigeneous populations from
      Siberia, Mongolia and Ural showed, that the ancient Siberian population is one of
      the ancestors of the modern population of Siberia. From genetic distance, in the
      assumption of constant nucleotide substitution rate, we estimated the divergence
      time between the Neolithic and the modern Siberian population. This divergence
      time (5572 years ago) is conformed to the age of skeletal remains (5542-5652
      years). With use of the 14C dates of the skeletal remains, nucleotide
      substitution rate in mtDNA was estimated as 1% sequence divergence for 8938-9115
      years.

PMID- 9569975
TI  - Study of the ApoB 3' HVR in Galicia (NW Spain). An interpopulational analysis.
AB  - The genetic polymorphism of ApoB 3' HVR was analyzed in 200 unrelated individuals
      from Galicia, North-West Spain, using the polymerase chain reaction followed by
      horizontal electrophoresis in polyacrylamide gels and silver staining. Up to 17
      alleles were detected in this way and a heterozygosity index of 77% was obtained.
      Significant deviations from Hardy-Weinberg equilibrium were detected using the
      conventional Pearson's chi 2, while the application of an exact test did not
      bring about significant values. A Correspondence Analysis among world populations
      resulted in clustering of the human major groups, although the lack of group
      specific alleles and the limited discrimination power found among Caucasian
      populations limit the usefulness of this locus in population genetic studies to
      some extent, despite its high degree of genetic variability.

PMID- 9569974
TI  - Molecular genetic sex determination of Medieval human remains from north Russia:
      comparison with archaeological and anthropological criteria.
AB  - Sex determination presents a difficult problem in archaeology and anthropology in
      cases of fragmentary or juvenile remains, and where grave goods are absent. Here,
      a molecular genetic analysis of the sex of human remain from the Early Medieval
      cemetery at Nefedievo, North Russia, was carried out and the results were
      compared with archaeological and anthropological data. Teeth without cavities (15
      samples) and bones (9 samples) were used as the ancient DNA source. The
      repetitive sequences in DYZ1, DYZ3, DXZ3 loci, and a unique sequence in the first
      intron of the X-Y homologous gene amelogenin, were amplified. Sex was determined
      in 87.5% of the samples by archaeological criteria, in 95.8% of the samples by
      anthropological methods, and in 79.2% of the samples by DNA analysis. PCR allowed
      the sex of infant's remains to be identified in individual where the sex could
      not be determined by anthropological methods and in three remains where sex could
      not be inferred from archaeological data. Uneven preservation of nuclear DNA loci
      was evident.

PMID- 9569976
TI  - [Haptoglobin (HPA)-subtypes in Swiss populations].
AB  - A subtyping of the haptoglobins of thirteen small Swiss populations, who live in
      mountainous regions of the Alps, and four larger Swiss populations has been
      undertaken. The impact of population and sample size on allele frequencies is
      discussed.

PMID- 9569977
TI  - [Hemo-genetic studies of an old isolate from the Lower Rhine].
AB  - In an isolate at the Lower Rhine region (North Rhine-Westphalia, Germany) 28
      haemogenetic systems have been studied. The immigrants had come mostly from the
      eastern Hunsruck about 250 years ago. The results have been compared with data
      from the Lower Rhine region, from Dusseldorf and from eastern Hunsruck (the main
      origin area of the "Pfalzer"). The cluster analysis shows relatively small
      genetic distances between these three samples; the population of the isolate is
      separated by distinct higher genetic distances. The results are discussed
      considering various population genetic factors.

PMID- 9569978
TI  - Frequency of homozygous null mutation at the glutathione-s-transferase M1 locus
      in some populations of Orissa, India.
AB  - GSTM1, one of the mu type glutathione-s-transferase isozymes in human, has been
      observed to be inherited dominantly, and the polymorphism of this gene can be
      detected by polymerase chain reaction (PCR). In this report we have determined
      the frequency of a homozygous deletion mutation of the GSTM1 gene in some
      populations of the Sundergarh District in Orissa, India. About 24% of unrelated
      individuals (n = 72) were detected to carry this deletion mutation in homozygous
      form. Possible implications of this homozygous deletion are discussed.

PMID- 9569979
TI  - Anthropometry and strength relationship: male-female differences.
AB  - Based upon 303 students from the Complutense University at Madrid (100 males and
      203 females), aged between 21 and 29 years, the results of nine anthropometric
      measurements and four strength tests were evaluated. Males and females were
      analyzed separately in order to determine whether the relationship of body
      typology to physical performance varies according to gender. Regarding strength,
      maximum gender differences were observed for pulling strength (females: 53% of
      male values), followed by hand grip (59%) and vertical jump (66%). In general,
      correlations among variables were significant (anthropometric, strength, and
      anthropometric/strength). Principal component analysis revealed, that for women
      the vertical jump could be interpretated as more dependent on trunk length than
      on height or body size. Body size was relevant with respect to static strength.
      For males the vertical jump appeared to be more related to longitudinal
      dimensions than for females, while static strength had more to do with body mass
      (weight) than with body size (height).

PMID- 9569980
TI  - Relationship between menarcheal age and nutritional anthropometry in urban girls
      of the Howrah District, West Bengal, India.
AB  - The present paper deals with the menarche and nutritional anthropometry among
      Bengali girls aged 9 to 16 years (n = 645) living in the city of Howrah (West
      Bengal, India). The result show that within the same socioeconomic group early
      menarche girls were heavier and taller than the late menarche girls. There is a
      significant difference between not attained menarche (NAM) and attained menarche
      (AM) girls aged 12 and 13 years for height and for 12 to 14 years in case of
      weight.

PMID- 9569981
TI  - Secular change in the torsional angle of Japanese femora.
AB  - The torsion angle of the Japanese femora of the early modern Edo (early and late
      series) and modern periods were measured. In the modern period, this angle is in
      males and females significantly larger than in the early series of the early
      modern Edo period and shows a gradual increase from the early modern Edo to the
      modern period. It is was always larger in females than in males. This change may
      be in part due to sedentary habits or living posture of the latter half in the
      early modern Edo period.

PMID- 9569982
TI  - Differences of the reconstructed stature in an early Medieval population
      depending on Pearson's regression equations.
AB  - On the basis of 238 male and 230 female skeletons, derived from a Medieval
      cemetery from Gruczno, Northern Poland, limb bones' proportion was determined.
      Substantial differences (d > 1 standard deviation) were established in 30% of the
      individuals, which, according to the relative relations among the separate bones,
      were divided into 6 groups. For separate individuals of each group a body height
      was calculated on the basis of Pearson's regression equation (Rosing 1988) as
      well as separately their arithmetic means for single limb bones and for two
      bones. The analysis of the absolute differences (the average and maximum values)
      among all the reconstructed body heights show that the calculated body height
      depends on the limb proportion. The degree oft the dependence does not seem to
      depend on the limb proportion group because the most significant differences for
      both sexes are connected with other proportion groups. The differences in the
      reconstructed body height are larger for the female skeletons.

PMID- 9569983
TI  - [Phylogenetic aspects of laterality].
AB  - The human being is not only characterized by the ability of abstract thinking,
      upright walking and speaking, but also by a strong and differentiate functional
      asymmetry. The great majority are right-handers, showing a left-cerebrally
      dominance for language and praxis. It is very important to know the period when
      the human laterality of functions is evolved. Human beings of all races and
      cultures appear to have been predominantly right-handed since the earliest
      records were made. The time when right-handedness emerged in human evolution is a
      matter of some dispute. Because of poor record-keeping in prehistoric times,
      statements about the evolution of laterality in human beings must be based
      largely on speculation. The present review summarizes the prehistoric data
      concerning handedness and cerebral laterality. It is confirmed that laterality is
      not evolved in the last thousand years but it seems that lateralization of
      functions is the result of a protracted process elapsing perhaps several million
      years ago. Moreover this paper discusses the genesis and reasons of laterality.

PMID- 9569984
TI  - Discrimination of hardness by human teeth apparently not involving periodontal
      receptors.
AB  - Periodontal receptors are generally thought to provide the input used to detect
      the hardness of food. Whether hardness can be sensed by teeth without periodontal
      assistance was tested here. A bite-force transducer was sandwiched between a hard
      acrylic strip on one side and rubber on the other side, both sides being covered
      with masking tape to prevent participants from sensing a difference in touch.
      Participants were asked to increase the bite force on the sandwich until, and if,
      they could detect which material, hard acrylic or rubber, was on the upper side.
      The positions of acrylic and rubber were randomly chosen. Fifteen participants
      each undertook three separate experiments each involving 10 tests using (1) bare
      incisors, (2) incisors capped with acrylic and (3) bare molars. The accuracy of
      responses and the direction and magnitude of bite forces were recorded.
      Participants most correctly detected the surfaces with bare incisors (91%
      correct, SD = 11%). Performance was significantly worse with capped incisors
      (79%, SD = 19%) (p < 0.01) and worse still with molars (57%, SD = 24%) (p <
      0.001). The detection threshold using bare incisors was increased in 14 out of
      the 15 participants when the incisors were capped, but the increase was
      statistically significant (0.002 < p < 0.01) in only six of them. The molar
      threshold was significantly increased (0.002 < p < 0.01) in comparison with the
      bare incisor threshold in 12 of 15 participants. There was no correlation between
      bite direction and the position of the rubber. Because in each trial the upper
      and lower periodontal input was the same whether the rubber was on the top or on
      the bottom, it was concluded that the periodontal ligament was not involved. The
      observed discrimination was probably based on a difference in the pressure on the
      upper and lower teeth. Incisal edges sank more deeply into the rubber and reduced
      the pressure (force/unit area) on a tooth crown.

PMID- 9569985
TI  - Sex-dependent differences in the concentrations of the principal
      neurotransmitters, noradrenaline and acetylcholine, in the three major salivary
      glands of mice.
AB  - The concentrations of principal neurotransmitters in the submandibular, parotid
      and sublingual glands were compared between two pairs of age-matched male and
      female ddY mice, one pair consisting of 4-week-old and the other 8-week-old
      animals. Sex-dependent differences in both noradrenaline and acetylcholine
      concentrations were observed only in the submandibular gland, although each
      neurotransmitter showed distinct features. The acetylcholine concentration in the
      submandibular gland was higher in the female at both ages, whereas the
      noradrenaline concentration was higher in the female at the age of 4 weeks but
      became higher in the male by the age of 8 weeks. On the other hand, the total
      amounts of noradrenaline and acetylcholine per submandibular gland were already
      greater in the male at 4 weeks, and the male parotid and sublingual glands also
      had a greater noradrenaline content by 4 weeks and 8 weeks, respectively. Each
      type of gland had similar growth rates over the 4-week period, and the male
      submandibular and parotid glands were heavier than the female. In addition, each
      type of gland had its characteristic ratio of noradrenaline to acetylcholine
      concentration, which did not differ between the sexes and remained in similar
      basic patterns during the period examined, except for the submandibular gland of
      8-week-old male mice, which developed greater amounts of the sympathetic
      neurotransmitter noradrenaline.

PMID- 9569987
TI  - Asymmetry in the occlusal morphology of first permanent molars in 45,X/46,XX
      mosaics.
AB  - The genetic control of dental morphology is affected by various chromosomal
      aberrations, and morphological changes familiar to specific aneuploidies can be
      distinguished in many cases. Asymmetry between bilateral teeth in the dental arch
      in laboratory animals shows increased expression after exposure to external
      stress during development. Bilateral asymmetry in occlusal cuspal morphology has
      not been widely used as a means of odontometric examination, partly because
      accurate and reliable methods are not commonly available. The aim here was to
      examine linear and angular variables of the occlusal morphology of maxillary and
      mandibular first permanent molars in three dimensions in individuals with
      45,X/46,XX mosaicism and to find out if this aneuploidism causes deviations from
      normal development and increased asymmetry in bilateral variables of the occlusal
      surface. The participants were five females with 45,X/46,XX chromosome
      constitution, whose karyotypes were confirmed by cytogenetic tests of skin
      fibroblasts. The controls were 10 first-degree female relatives of the mosaic
      patients with normal 46,XX chromosome constitution. The method of measuring the
      three-dimensional morphology of occlusal surfaces was based on a machine-vision
      technique using a single video-imaging camera. An apparent increase in asymmetry
      of occlusal morphology in first permanent molars in 45,X/46,XX mosaics was found.
      As there was evidence of directional asymmetry, it is possible that different
      cell lines regulated by discrete genes cause the directionality.

PMID- 9569986
TI  - Supernatant cytotoxicity and proteolytic activity of selected oral bacteria
      against human gingival fibroblasts in vitro.
AB  - The purpose of this study was to determine if endodontic bacterial act in vitro
      on human gingival fibroblast functions via extracellular products. The bacteria
      used were Prevotella nigrescens, Capnocytophaga ochracea, Peptostreptoccocus
      micros and Actinobacillus actinomycetemcomitans. Supernatants were collected from
      bacterial cultures at the beginning of the stationary phase when their density
      was similar. Toxins that inhibited fibroblast proliferation were found in all
      culture supernatants of Gram-positive or Gram-negative bacterial strains, except
      for Prev. nigrescens. The cytotoxicity of A. actinomycetemcomitans supernatant
      was about 1000 fold higher than the others. This supernatant diluted to 1/1000
      led to total fibroblast growth inhibition whereas only 25% growth inhibition was
      obtained with Capn. ochracea and Pept. micros diluted to 1/10. Bacterial
      supernatant proteolytic activity was investigated in confluent fibroblast
      cultures that were incubated for 48 hr with each of the supernatants diluted to
      1/2 except for A. actinomycetemcomitans supernatant diluted to 1/20. Indirect
      immunofluorescence studies of extracellular-matrix molecules, followed by
      immunoelectrophoretic analysis of extracts of whole-cell layers, demonstrated
      that only conditioned medium of Prev. nigrescens had a proteolytic activity
      capable of degrading the greater part of type I collagen and fibronectin fibres
      in the extracellular matrix.

PMID- 9569989
TI  - Investigation of the clinical value of total saliva flow rates.
AB  - The symptom of dry mouth was correlated with unstimulated (UWSFR) and stimulated
      (SWSFR) whole-saliva flow rate on chewing medical paraffin in 62 patients with
      dry-mouth complaints (30 with Sjogren's syndrome, 32 with sialosis) and 23
      controls. The symptom of dry mouth was classified into grades 0,1,2,3,4 according
      to a Treatment Emergent Symptom Scale (TESS). UWSFR and SWSFR were determined
      after fasting in the morning. UWSFR was 0.070 +/- 0.089 ml/min in Sjogren's
      syndrome, 0.175 +/- 0.115 ml/min in sialosis, 0.330 +/- 0.188 ml/min in controls.
      SWSFR was 0.709 +/- 0.720 ml/min in Sjogren's syndrome, 1.561 +/- 0.867 ml/min in
      sialosis, 1.894 +/- 0.661 ml/min in controls. A highly significant correlation
      was found between TESS score and UWSFR and between TESS score and SWSFR. Only
      UWSFR was decreased in the patients with a TESS score of 1 or 2, while both UWSFR
      and SWSFR were significantly decreased in the patients with TESS scores of 3, 4.
      It is concluded that UWSFR is more sensitive in relation to dry-mouth complaints
      than SWSFR, and that a mild dry mouth is mainly related to decreased UWSFR.

PMID- 9569988
TI  - Stabilization of the glucan-binding lectin of Streptococcus sobrinus by specific
      ligand.
AB  - Cell suspensions of Streptococcus sobrinus can be aggregated by high molecular
      weight alpha-1,6 glucans. The aggregation depends on the fidelity of a cell wall
      bound, glucan-binding lectin (GBL). It is thought that the lectin may play a part
      in the sucrose-dependent accretion of streptococci in dental plaques. Results
      showed that the anionic detergent, sodium dodecyl sulphate (SDS) was a potent
      inhibitor of the lectin. When cells were incubated in SDS and washed to remove
      the detergent, lectin activity was diminished. Following incubation of the cells
      with SDS in the presence of glucan T-10, a low molecular-weight alpha-1,6 glucan,
      the loss of activity was less pronounced, suggesting that the glucan afforded
      partial protection against denaturation. Urea and guanidine hydrochloride were
      good inhibitors of the lectin, but, unlike SDS, were not able to inhibit it
      irreversibly, except at very high concentrations. Cationic detergents, such as
      cetylpyridinium bromide (and chloride), also irreversibly denatured the
      streptococcal lectin, but were not as effective as SDS in abolishing its
      activity. The results suggest that alpha-1,6 glucan stabilizes the GBL of S.
      sobrinus, rendering it more resistant to the effect of chaotropes. This may be
      one reason why dental plaques tend to resist detergents in dentrifices.

PMID- 9569990
TI  - Physiological tremor in human jaw-muscle system.
AB  - Small, quasi-rhythmical tremor of the jaw occurs at rest and during voluntary
      movements. In peripheral limbs, tremor consists of a component due to mechanical
      resonance properties of the system, and a neurogenic component mediated by a
      central pacemaker or neural loops. The present study attempted to determine if
      these components were present in jaw tremor measured with a position transducer
      held lightly between the incisors. When weights were suspended from the mandible,
      the tremor frequency was unaltered; sharp taps delivered to the jaw did not
      elicit any kind of damped oscillations of the system. These findings indicated
      the absence of mechanical resonance in the system. No correlation of the tremor
      signal with the electrocardiogram was found. However, a strong correlation was
      found between the rectified electromyographic signals recorded over the masseter
      muscles and the tremor signal, where the electromyographic signal preceded jaw
      movement by 20-30 msec. Frequency-domain analysis also showed positive peaks in a
      majority of coherence functions between electromyographic and tremor signals.
      These results suggested a strong neurogenic component of the tremor.

PMID- 9569991
TI  - The role of gingival mechanoreceptors in the reflex control of human jaw-closing
      muscles.
AB  - Electromyographic (EMG) experiments were undertaken to investigate the jaw
      reflexes evoked by activation of gingival receptors in 12 humans. EMG recordings
      were made from an active masseter muscle whilst ramp-plateau mechanical stimuli
      were applied to the gingiva. Stimuli with a constant rate of rise (0.2 N/msec)
      and a variable plateau force (up to 2 N), evoked a complex set of short- and long
      latency inhibitory and excitatory responses. These occurred as a sequence of
      inhibition-excitation-inhibition-excitation, although not all of these elements
      were seen on every occasion. The median thresholds of these four responses ranged
      from 0.5 to 1 N but overall there were no significant differences between them (p
      > 0.05, Friedman's ANOVA). In other experiments, the same reflexes were recorded
      in response to application to the gingiva of 1 N ramp-plateau stimuli (5 msec
      rise time) and 1 N tap stimuli applied to the adjacent tooth. The application of
      a local anaesthetic agent to the stimulated gingiva produced reductions in the
      mean magnitude of almost all the responses but these were significant (p < 0.05;
      ANOVA) only for the long-latency inhibitions evoked by ramping the gingiva and
      the long-latency excitations evoked by either stimulus. It is concluded that
      mechanoreceptors in the gingiva can mediate long-latency inhibitory and
      excitatory jaw reflexes, and that these receptors may also contribute to long
      latency reflexes evoked by tapping teeth. The scarcity of effects of gingival
      anaesthesia on the short-latency reflexes may be due to such responses being
      mediated by receptors deeper in the periodontium.

PMID- 9569992
TI  - Inhibition by glass-ionomer cements of protein synthesis by human gingival
      fibroblasts in continuous culture.
AB  - The effects of several glass-ionomer cements (Baseline and Chem Fil of De Trey;
      Ketac Fil and Ketac Bond of ESPE; Vitrebond and Vitremer of 3 M) on the protein
      synthesis of cultured gingival fibroblasts were studied. The presence of cements
      in the culture medium inhibited protein synthesis, although the relative
      effectiveness varied significantly. The cements tested have been ranked in three
      groups, group A (Chem Fil and Ketac Fil), group B (Ketac Bond and Baseline) and
      group C (Vitrebond and Vitremer), showing 50, 75 and 100% reduction in protein
      synthesis, respectively. Incubation of cells with medium previously conditioned
      by Baseline and Ketac Fil caused only transient inhibition of protein synthesis
      followed by almost complete recovery. This recovery was not observed when the
      medium was conditioned with Vitrebond. A characterization of the factors
      determining the inhibitory effect of one cement in each group was attempted. The
      cements, irrespective of the type, produced small but reproducible decreases in
      the pH of the medium but released fluoride ions to a different extent. Both
      changes in the pH of the medium and in the fluoride concentration inhibited
      protein synthesis by cultured gingival fibroblasts. The different action of
      cements can be explained, at least in part, by a differing release of fluoride
      ions.

PMID- 9569993
TI  - Cytotoxicity of photosensitizers camphorquinone and 9-fluorenone with visible
      light irradiation on a human submandibular-duct cell line in vitro.
AB  - The cytotoxic effect of two types of photosensitizers (camphorquinone, CQ, a
      widely used aliphatic type and 9-fluorenone, 9F, an aromatic type) in the
      presence of 2-dimethylaminoethyl methacrylate (DM) as a reducing agent with
      exposure to visible light (350-550 nm) was examined in a human cell line.
      Cytotoxicity was evaluated in terms of the percentage of cell survival, and the
      production of reactive oxygen in living single cells was measured with an
      adherent cell analysis and sorting laser cytometer and a peroxide indicator. The
      amount of reactive oxygen generated in the cells irradiated in the 9F (1 mM-3
      min) system was about 9-fold greater than under the same conditions in the CQ
      system. Similarly, the decrease in cell survival in the 9F system was about 10
      fold greater than in the CQ. Both the production of reactive oxygen in the cells
      and the decrease in cell survival paralleled the concentration of
      photosensitizers and the irradiation time. Although the cell-damaging effects
      with the CQ system were mild, at a higher dose (10 mM) and longer irradiation
      time (24 min) it produced cell survival equal to that in the 9F (1 mM-3 min)
      system. These results suggest that in the case of irradiated photosensitizer
      systems, 9F was much more damaging to the cells than CQ, which damage probably
      occurred via free radicals involving reactive oxygen generation.

PMID- 9569994
TI  - The effect of altered functional forces on the expression of bone-matrix proteins
      in developing mouse mandibular condyle.
AB  - Mechanical forces are known to have an effect on bone formation, maintenance and
      remodelling, and there is evidence that the development of the mandibular condyle
      in the rat is influenced by the consistency of the diet. Here a mouse model was
      used to investigate the relation between food, condylar development and the
      expression of bone sialoprotein (BSP), osteopontin (OPN), osteocalcin (OC) and
      type 1 collagen (COL I). Twenty-four 19-day-old male mice were randomly divided
      into three groups. Groups 1 and 2 were fed hard pellets and soft powdered food,
      respectively, for 2 weeks. Group 3 mice were fed soft food for 1 week followed by
      a week of hard pellets. Incisors of mice in groups 2 and 3 were trimmed twice a
      week to reduce occlusal forces. After killing the animals, mandibular condyles
      were collected for RNA extraction, in situ hybridization and immunohistochemical
      analyses. Histological sections showed that the condyles of mice in group 2 were
      underdeveloped, with a thinner layer of cartilage and fewer bone trabeculae.
      Northern hybridization of total RNA of the condyle from mice in this soft-food
      group also exhibited a significant decrease in the amounts of BSP, OPN, OC and
      COL I, representing 79%, 75%, 77% and 79% respectively, of that from mice fed
      hard food. In situ hybridization of these bone-matrix proteins demonstrated
      signals in bone-forming cells and BSP mRNA was also seen in the hypertrophic
      cartilage cells in the developing condyle. Immunohistochemical study demonstrated
      an obvious difference in the intensity of staining, especially for BSP. Results
      from group 3 were similar to those from group 1. The observed decrease in bone
      matrix-protein expression confirms that the consistency of the diet affects the
      development of the mouse mandibular condyle and that a soft diet diminishes the
      rate of bone formation.

PMID- 9569996
TI  - Pharmacokinetics and urinary excretion of DMXBA (GTS-21), a compound enhancing
      cognition.
AB  - DMXBA (3-(2,4-dimethoxybenzylidene)-anabaseine, also known as GTS-21) is
      currently being tested as a possible pharmacological treatment of cognitive
      dysfunction in Alzheimer's disease. In this study, plasma and brain
      pharmacokinetics as well as urinary excretion of this compound have been
      evaluated in adult rats. DMXBA concentrations were determined by HPLC. Following
      a 5 mg kg-1 iv dose, DMXBA plasma concentration declined bi-exponentially with
      mean (+/- SE) absorption and elimination half-lives of 0.71 +/- 0.28 and 3.71 +/-
      1.12 h, respectively. The apparent steady state volume of distribution was 2150
      +/- 433 mL kg-1, total body clearance was 1480 +/- 273 mL h-1 kg-1, and AUC0
      infinity was 3790 +/- 630 ng h mL-1. Orally administered DMXBA was rapidly
      absorbed. After oral administration of 10 mg kg-1, a peak plasma concentration of
      1010 +/- 212 ng mL-1 was observed at 10 min after dosing. Elimination half-life
      was 1.740 +/- 0.34 h, and AUC0-infinity was 1440 +/- 358 ng h mL-1. DMXBA peak
      brain concentration after oral administration was 664 +/- 103 ng g-1 tissue, with
      an essentially constant brain-plasma concentration ratio of 2.61 +/- 0.34, which
      indicates that the drug readily passes across the blood-brain barrier. Serum
      protein binding was 80.3 +/- 1.1%. Apparent oral bioavailability was 19%. Renal
      clearance (21.8 mL h-1 kg-1) was less than 2% of the total clearance (1480 +/-
      273 mL h-1 kg-1); urinary excretion of unchanged DMXBA over a 96 h period
      accounted for only 0.28 +/- 0.03% of the total orally administered dose. Our data
      indicates that DMXBA oral bioavailability is primarily limited by hepatic
      metabolism.

PMID- 9569995
TI  - Pharmacokinetic and pharmacodynamic changes of azosemide after intravenous and
      oral administration of azosemide to uranyl nitrate-induced acute renal failure
      rats.
AB  - The pharmacokinetic and pharmacodynamic differences of azosemide were
      investigated after intravenous (i.v.) and oral administration of azosemide, 10 mg
      kg-1, to the control and uranyl nitrate-induced acute renal failure (U-ARF) rats.
      After IV administration, the plasma concentrations of azosemide were
      significantly higher in the U-ARF rats and this resulted in a significant
      increase in AUC (2520 versus 3680 micrograms min mL-1) and significant decrease
      in Cl (3.96 versus 2.72 mL min-1 kg-1) of azosemide. The significant decrease in
      Cl in the U-ARF rats was due to the significant decrease in Clr of azosemide
      (1.55 versus 0.00913 mL min-1 kg-1) due to the decrease in kidney function in the
      U-ARF rats. After IV administration, the urine output (38.5 versus 8.45 mL 100 g
      1 body weight) and urinary excretion of sodium (4.60 versus 0.420 mmol 100 g-1
      body weight) decreased significantly in the U-ARF rats. After oral
      administration, the AUC0-8 h of azosemide decreased significantly (215 versus 135
      micrograms min mL-1) in the U-ARF rats possibly due to the decreased GI
      absorption of azosemide. After oral administration, the 24-h urine output
      decreased considerably (16.1 versus 11.2 mL 100 g-1 body weight, p < 0.098) and
      the 24-h urinary excretion of sodium (1.74 versus 0.777 mmol 100 g-1 body weight)
      decreased significantly in the U-ARF rats. The i.v. and oral doses of azosemide
      needed to be modified in the acute renal failure patients if the present rat data
      could be extrapolated to humans.

PMID- 9569997
TI  - Assessment of effect of food, gender, and intra-subject variability in the
      pharmacokinetics of avitriptan.
AB  - The objectives of this study were to assess the effect of food and gender on the
      pharmacokinetics of avitripan. A group of 12 healthy men and 12 healthy women was
      administered a single 50 mg dose of avitriptan capsule under fasting conditions
      and 5 min after a high-fat breakfast. The two treatments were repeated in a
      replicate design to assess the intra-subject variability in the pharmacokinetics
      of avitriptan under fasted and fed conditions. There was a 1 week washout between
      treatments. Serial blood samples were collected over 24 h after dosing and
      analyzed by a validated HPLC method for avitriptan. The mean (SD) peak
      concentrations (Cmax) were 168 (86.4) ng mL-1 in the fasted condition and 57.3
      (34.8) ng mL-1 in the fed condition in males and females combined. The
      corresponding areas under the plasma concentration curve (AUC) were 335 (162) and
      185 (64.5) ng h mL-1, respectively. Both Cmax and AUC were significantly reduced
      in the fed condition. In addition, the time to peak concentration (tmax) was
      significantly delayed from a median of 45 min to 2 h after the high-fat
      breakfast. The clinical significance of this food effect is unclear at the
      present time. There were no gender differences nor a gender by food interaction
      in the pharmacokinetics of avitriptan. The intra- and inter-subject variability
      (%CV) in the Cmax and AUC of avitriptan in the fasted and fed conditions ranged
      from 10 to 60% in male and female subjects.

PMID- 9569998
TI  - Dose-proportional pharmacokinetics of a new 5-lipoxygenase inhibitor, ABT-761, in
      healthy volunteers.
AB  - ABT-761, a new potent 5-lipoxygenase inhibitor, is under development for the
      treatment of asthma. The pharmacokinetics and dose proportionality of ABT-761
      after single doses (10-160 mg) of ABT-761 in 24 healthy male volunteers were
      investigated in a double-blind, placebo-controlled study. The compound was well
      tolerated, with no clinically significant effects on vital sign measurements,
      hematological parameters, clinical chemistry, urinalysis, or electrocardiogram.
      The plasma concentration-time profile of ABT-761 indicates that the drug declines
      in a monoexponential fashion after moderately slow absorption, with a tmax value
      of approximately 4 h. The terminal elimination t1/2 averaged 15 h, and was dose
      independent. ABT-761 mean values of Cmax and AUC were linearly related to drug
      dose. ABT-761 is well tolerated in healthy volunteers and the pharmacokinetics
      are linear in the single-dose range between 10 and 160 mg.

PMID- 9569999
TI  - The effects of non-steroidal anti-inflammatory drugs on the disposition of
      methotrexate in patients with rheumatoid arthritis.
AB  - We have studied the pharmacokinetics of methotrexate in patients with rheumatoid
      arthritis concurrently taking the most commonly used non-steroidal anti
      inflammatory drugs (NSAIDs), aspirin, diclofenac, naproxen, indomethacin, and
      ibuprofen. The area under the curve, the total systemic clearance, the
      distribution volume, and the half-life of methotrexate in patients receiving
      concurrent NSAID therapy did not change significantly (at p < 0.05). Concurrent
      treatment with NSAIDs resulted in increased inter-patient variability of
      methotrexate concentration, possibly as a result of biochemical interactions;
      however, it does not appear clinically relevant. The data suggest that the NSAIDs
      do not significantly affect the disposition of methotrexate, contrary to some of
      the earlier reports.

PMID- 9570000
TI  - Determination of the population pharmacokinetic parameters of sustained-release
      and enteric-coated oral formulations, and the suppository formulation of
      diclofenac sodium by simultaneous data fitting using NONMEM.
AB  - Data from sustained-release and enteric-coated oral formulations, and the
      suppository formulation of diclofenac sodium are fitted simultaneously using
      NONMEM and the general linear model, ADVAN 5. Absorption and disposition
      parameters, serum levels, and absorption profiles were determined. The in vivo
      absorption profiles were determined using the program TOPFIT. The in vivo
      absorption for the sustained-release formulation is slow first order and follows
      a flip-flop model since disposition rate constants are greater than absorption
      rate constants. Absorption from the enteric-coated form is essentially complete
      (> or = 95%) at about 7.5 h, while it is 95% complete at 24 h from the sustained
      release formulation. This suggests likely absorption from the colon in the case
      of the sustained-release formulation since absorption is only 75% complete during
      the first 10 h. The sustained-release relative bioavailability is 90-99%.
      Absorption from the suppository is essentially complete at about 4.5 h. However,
      the relative bioavailability of the suppository formulation is low (55%), since
      defecation may remove the drug from the absorption site before complete
      absorption.

PMID- 9570001
TI  - Grapefruit juice and orange juice effects on the bioavailability of nifedipine in
      the rat.
AB  - Previous studies with rats indicate that nifedipine undergoes both hepatic and
      extrahepatic presystemic metabolism after peroral (po) administration, and that
      its bioavailability is increased and absorption delayed by concomitant
      administration of grapefruit juice concentrate (GJC). Hence, the effects of GJC
      could be to delay stomach emptying and inhibit nifedipine metabolism in the small
      intestinal wall and liver or, alternatively, to impede nifedipine absorption
      until reaching the large intestine where gut wall presystemic metabolism is not a
      factor. The mechanism(s) of action of GJC might be partially resolved by
      comparison with orange juice concentrate (OJC), which has a similar consistency
      but lacks inhibitory effects on nifedipine presystemic metabolism, and also by
      giving regular-strength solutions of the two juices, both on which should not
      significantly affect stomach emptying. This study compared the po bioavailability
      of nifedipine (6 mg kg-1) in male Sprague-Dawley rats coadministered GJC, OJC,
      grapefruit juice regular strength (GJRS), orange juice regular strength (OJRS),
      or (tap) water. Nifedipine plasma concentration-time profiles in the GJRS, OJRS,
      and (tap) water groups displayed a single peak. Both GJC and OJC groups have
      double-peak profiles (indicating delayed gastric emptying); however, the majority
      of the nifedipine dose in both cases was absorbed during the interval of the
      second peak, which occurred several hours postdosing. GJC significantly increased
      nifedipine bioavailability (relative bioavailability 2.02, compared with (tap)
      water), indicating that GJC may affect both extrahepatic and hepatic first-pass
      metabolism, although a reduction in systemic nifedipine clearance cannot be ruled
      out. Surprisingly, GJRS had no significant effect on nifedipine bioavailability.
      OJC did not increase nifedipine bioavailability, further suggesting that the
      delay in nifedipine absorption by GJC or OJC results from delayed gastric
      emptying.

PMID- 9570002
TI  - Pharmacokinetics and pharmacodynamics of CI-992 following intravenous and oral
      administration to cynomolgus monkeys.
AB  - The purpose of this study was to characterize CI-992 pharmacokinetics and
      pharmacokinetics/pharmacodynamics (PK/PD) in sodium deplete monkeys. Panels of
      monkeys were administered CI-992 as a 1 h intravenous infusions (0.1 and 1 mg kg
      1) or as single oral doses (0, 10, 50, and 100 mg kg-1). Mean arterial blood
      pressure (MABP) was monitored and serial blood samples were collected up to 24 h
      postdose. Plasma CI-992 concentrations were quantitated by radioimmunoassay.
      Pharmacokinetic parameters were calculated by noncompartmental methods. PK/PD
      relationships were assessed by standard methods. Oral bioavailability of CI-992
      in the monkeys was < 2%; steady-state volume of distribution was 0.67 L kg-1;
      clearance was 10.4 mL min-1 kg-1. Following oral administration, tmax generally
      occurred 6-9 h postadministration; plasma CI-992 concentrations increased with
      increasing dose between 10 and 50 mg kg-1, but did not change appreciably from 50
      to 100 mg kg-1. After intravenous administration, change in MABP was correlated
      with plasma CI-992 concentration through an effect compartment model in which the
      maximum achievable effect was a 22 mm Hg decrease in MABP; the steady-state
      concentration which produced half the maximum effect was 11 ng mL-1. Following
      the 10 mg kg-1 oral dose the maximum decrease in MABP was 19.1 mm Hg; higher
      doses did not produce greater maximum response but increased the duration of
      action. In contrast to observations following intravenous administration, a trend
      for decreasing MABP with increasing plasma CI-992 was not apparent following oral
      CI-992 administration.

PMID- 9570003
TI  - The effect of lymphatic oedema on the uptake of colloids to the lymph nodes.
AB  - The majority of pathological conditions of the lymphatic system can result in
      some degree of lymphoedema, which in turn causes a reduced rate of lymph flow. In
      some cases, such as when nodes are invaded by tumour metastases, blockage of the
      lymphatic vessels may occur. In order to investigate the effect of such pathology
      on nanosphere uptake in regional lymph nodes, the fate of model polystyrene
      nanospheres, surface modified with block co-polymers of the poloxamine series,
      was determined following subcutaneous administration in a rat model with
      lymphoedema (induced by the administration of lambda-carrageenan). A drastic
      reduction of injection site drainage and lymph node uptake of nanospheres was
      observed in the inflammation model compared to control animals. The observations
      suggest that biodegradable nanospheres based on these will be suitable for the
      detection of oedema in the lymphatic system.

PMID- 9570004
TI  - A physiologically based kidney model for the renal clearance of ranitidine and
      the interaction with cimetidine and probenecid in the dog.
AB  - Ranitidine renal clearance was investigated in the beagle dog with or without
      concomitant infusion of cimetidine or probenecid. Ranitidine was excreted mainly
      by renal tubular secretion. Plasma clearance was reduced by probenecid from 198
      +/- 47 to 119 +/- 41 mL min-1 (mean +/- SD.); renal clearance was reduced from
      104 +/- 33 to 54 +/- 24 mL min-1 (p < 0.02) by probenecid and to 89 +/- 37 mL min
      1 (NS) by cimetidine. Plasma and urine data were analysed simultaneously with a
      physiologically based kidney model and were both described adequately by the
      model, although tubular secretion could not be fully characterized as no
      saturation was achieved despite high dosages. Tubular secretion of ranitidine was
      simplified to first-order brush-border and basolateral transport across the
      proximal tubular cell. Basolateral transport was reduced (from 18.4 +/- 7.8 to
      13.6 +/- 10.3 min-1 by cimetidine and 3.9 +/- 3.1 min-1 by probenecid), whereas
      no effect on brush-border exit was found. Estimated inhibition constants of
      cimetidine and probenecid were 62 and 4 micrograms mL-1, respectively.
      Summarizing, ranitidine renal pharmacokinetics were accurately described by the
      physiologically based kidney model presented in this paper. Model calculations
      suggest that interaction with cimetidine and probenecid results from competition
      for basolateral ranitidine uptake into tubular cells.

PMID- 9570005
TI  - Sequence-specific antibodies to connexins block intercellular calcium signaling
      through gap junctions.
AB  - Mechanical stimulation of a single cell in primary airway epithelial cell
      cultures induces an intercellular Ca2+ wave that has been proposed to be mediated
      via gap junctions. To investigate directly the role of gap junctions in this
      multicellular response, the effects of intracellularly-loaded sequence-specific
      connexin (gap junction) antibodies on the propagation of intercellular Ca2+ waves
      were evaluated. Electroporation of antibodies to the cytosolic loop (Des 1,
      generated to amino acids 102-112 + 116-124; and Des 5, amino acids 108-119), or
      to the carboxyl tail (Gap 9, amino acids 264-283) of connexin 32 inhibited the
      propagation of intercellular Ca2+ waves. The inhibitory effect of Des 1 antibody
      was competitively reversed by the co-loading of a peptide derived from a similar
      cytosolic loop sequence (Des 5 peptide). Conversely, the inhibitory effects on
      intercellular Ca2+ wave propagation of Gap 9 antibody was not altered by co
      loading with the Des 5 peptide. Antibodies raised to peptide sequences within the
      extracellular loop (Gap 11, amino acids 151-187), or the cytoplasmically located
      amino terminus (Gap 10, amino acids 1-21) of connexin 32 did not inhibit
      mechanically-induced intercellular communication. Also ineffective in perturbing
      intercellular communication were antibodies raised to peptide sequences of the
      cytosolic loops of connexin 43 (Gap 15, amino acids 131-142) or connexin 26 (Des
      3, amino acids 106-119). These data suggest that mechanically-induced Ca2+ waves
      in airway cell cultures are propagated through gap junctions made up of connexin
      32 proteins.

PMID- 9570006
TI  - Agonist-induced down-regulation of type 1 and type 3 inositol 1,4,5-trisphosphate
      receptors in A7r5 and DDT1 MF-2 smooth muscle cells.
AB  - Prolonged stimulation of rat A7r5 aortic smooth muscle cells with 3 microM
      vasopressin, or of hamster DDT1 MF-2 smooth muscle cells with 10 microM
      bradykinin or 100 microM histamine led within 4 h to a 40-50% down-regulation of
      the type 1 InsP3 receptor (InsP3R-1) and of the type 3 InsP3 receptor (InsP3R-3).
      InsP3R down-regulation was a cell- and agonist-specific process, since several
      other agonists acting on PLC-coupled receptors did not change the expression
      level of the InsP3R isoforms in these cell types and since no agonist-induced
      down-regulation of InsP3Rs was observed in HeLa cells. Down-regulation of InsP3Rs
      was prevented by an inhibitor of proteasomal protease activity, N-acetyl-Leu-Leu
      norleucinal (ALLN). The Ca2+ channel blocker verapamil (2 microM) also induced
      InsP3R-1 down-regulation (43%) in A7r5 cells, which was inhibited by ALLN. In
      A7r5 cells transiently transfected with a cDNA construct, bearing a luciferase
      coding sequence under control of the rat InsP3R-1 promoter, reduced luciferase
      activity could be demonstrated upon stimulation of cells with vasopressin or
      verapamil. Thus, besides enhanced protein degradation, a reduction of InsP3R
      promoter activity might contribute to the down-regulation of InsP3Rs in A7r5
      cells. We next investigated the effect of InsP3R down-regulation on Ca2+
      responses in A7r5 cells. A rightward shift in the dose-response curve for InsP3
      induced Ca2+ release was observed in permeabilized monolayers of vasopressin
      pretreated A7r5 cells (EC50 630 nM and 400 nM for pretreated and non-pretreated
      cells, respectively). The Ca2+ responses to threshold doses of vasopressin were
      markedly reduced in intact vasopressin-pretreated cells. We conclude that
      prolonged agonist-exposure leads to down-regulation of InsP3Rs in A7r5 and DDT,
      MF-2 smooth muscle cells. The mechanism of down-regulation likely involves
      proteasomal degradation and reduction of InsP3R promoter activity. Moreover, down
      regulation of InsP3Rs resulted in desensitization of Ca2+ release from InsP3
      sensitive stores.

PMID- 9570007
TI  - Fura-2 calcium signals in skeletal muscle fibres loaded with high concentrations
      of EGTA.
AB  - Fura-2 is one of the most frequently used fluorescent Ca indicator dyes; yet it
      has limitations in tracking large intracellular Ca transients due to its high
      affinity for Ca. Since high affinity is of advantage when small Ca changes are to
      be detected, we tried the application of Fura-2 in skeletal muscle fibres which
      had been loaded with 15 mM internal EGTA to eliminate contractile artifacts.
      Under these conditions, the free Ca transients are considerably reduced in
      amplitude and strong saturation of Fura-2 is avoided. Cut segments of isolated
      muscle fibres were voltage-clamped in a double vaseline gap set-up. In the
      presence of high internal EGTA, free Ca (as measured with the rapid
      metallochromic indicator antipyrylazo III) drops rapidly from one value to a
      lower quasi steady-state value at the end of a depolarizing voltage pulse. This
      property allowed inspection of the dissociation kinetics of Ca from Fura-2 in the
      myoplasmic environment. The dissociation rate constant koff in the fibre was
      determined from the time constant of the exponential decay of the Fura-2 signal
      as a function of the final level of free Ca. We obtained a value of 26 s-1 at the
      experimental temperature of 12 degrees C. Knowledge of koff in the cell is
      essential for reconstructing the time course of free Ca from indicator bound Ca
      and for estimating the time course of the rate of release from the sarcoplasmic
      reticulum. The described combination of high EGTA buffering with Fura-2
      fluorescence recording may be particularly useful for the determination of Ca
      release in small muscle cells.

PMID- 9570008
TI  - Voltage dependent calcium channels in adrenal glomerulosa cells and in insulin
      producing cells.
AB  - We have examined the structure and function of Ca2+ channels in excitable
      endocrine cell types, in rat adrenal glomerulosa cells and in two insulin
      producing cell types, the rat pancreatic beta cell and the INS-1 cell line. In
      previous studies on glomerulosa cells, we observed low (T-type) and high
      threshold (L-type) voltage dependent Ca2+ currents in addition to a K+ induced
      inward rectifying Ca2+ current (Igl). beta cells are known to exhibit T-, L- and
      N-type currents. We have now found that INS-1 cells also show low threshold (T
      type) and high threshold Ca2+ currents. The latter was further resolved by
      organic inhibitors into L-type and P/Q-type currents and no Igl was detected. The
      expression of the pore-forming alpha 1 subunit of voltage dependent Ca2+ channels
      was studied by means of reverse transcription-polymerase chain reaction (RT-PCR),
      followed by restriction enzyme mapping and/or sequencing. Both in glomerulosa and
      pancreatic beta cells, the neuroendocrine (D) class of the alpha 1 subunit, known
      to be responsible for L-type current, represents the majority of the PCR product.
      Comparable amounts of the neuroendocrine (D) and the neuronal A-type alpha 1
      subunits dominate the message in INS-1 cells. Different characteristics of Ca2+
      currents in these cell types is discussed in view of the channel repertoire.

PMID- 9570009
TI  - Kinetic basis of quantal calcium release from intracellular calcium stores.
AB  - The kinetics of Ca2+ release from canine cerebellum and rabbit skeletal muscle
      microsomes, mediated by the inositol 1,4,5-trisphosphate (IP3) receptor (IRC) and
      the ryanodine receptor (RyRC), respectively, were analyzed by a model, which
      considers that Ca2+ release channels undergo spontaneous inactivation. We found
      that: (i) both the initial rate of release (Vo) and the rate of inactivation (Vi)
      were saturable functions of the activating ligand concentration (CL); and (ii)
      the ratio of Vi/Vo, termed the relative tendency for inactivation, decreased with
      increasing CL. Equilibrium [3H]-IP3 binding studies, on the other hand, revealed
      the presence of one single class of non-co-operative IP3 sites in cerebellum
      membranes (Kdeq = 47 nM and Hill coefficient = 1.1). Based on the above Vi-Vo
      relationship and the IP3-binding data, we propose that quantal Ca2+ release
      through IRCs might be a result of spontaneous channel inactivation, whose rate is
      controlled by the ratio of IP3-occupied/free monomers in the tetrameric release
      channel units. Furthermore, because of the kinetic similarities between the IRC-
      and RyRC-mediated Ca2+ release processes, as well as between quantal Ca2+ release
      and channel adaptation, the same mechanism is also proposed to apply to the RyRC
      mediated Ca2+ release as well as to constitute the basis of release channel
      adaptation.

PMID- 9570010
TI  - Calcium store depletion activates two distinct calcium entry pathways in
      secretory cells of the blowfly salivary gland.
AB  - Ca2+ influx into secretory cells of the intact salivary gland of the blowfly
      Calliphora erythrocephala elicited by the agonist 5-hydroxytryptamine (5-HT) or
      the Ca2+ uptake inhibitor thapsigargin was studied by using Fura-2 and digital
      fluorescence imaging and by recordings of the transepithelial potential.
      Application of saturating [5-HT] in the absence of Ca2+ (Ca2+o) from the bathing
      saline did not affect the initial Ca2+ transient but greatly attenuated the
      subsequent sustained Ca2+ elevation observed in the presence of Ca2+o
      demonstrating that the latter component of the [Ca2+]i response is largely
      dependent on Ca2+ entry across the baso-lateral plasma membrane. La3+ or Gd3+ (10
      microM) mimicked the effects of the withdrawal of Ca2+o. Experimental attempts
      temporally to uncouple 5-HT stimulation and Ca2+ influx by withdrawal of Ca2+o
      during agonist application revealed a second Ca2+ entry pathway. This pathway was
      insensitive to 10 microM La3+ and produced transient [Ca2+]i increases whose
      amplitudes were a function of the [5-HT] during the preceding stimulation and
      that were selectively suppressed by 50 microM SK&F 96365. Both (10 microM) La(3+)
      insensitive [Ca2+]i transients and (10 microM) La3+ inhabitable tonic [Ca2+]i
      increases could be sequentially activated in the presence of 5-HT or thapsigargin
      (1 microM). These results indicate that Ca2+ store depletion by 5-HT or
      thapsigargin activates two distinct store-operated Ca2+ entry pathways, one of
      which supports tonic [Ca2+]i increases. The other is transiently activated, even
      under conditions that prohibit store refilling and does not significantly
      contribute to the [Ca2+]i responses evoked by saturating 5-HT concentrations.

PMID- 9570011
TI  - Does a decrease in subplasmalemmal Ca2+ explain how store-operated Ca2+ channels
      are opened?
AB  - The phenomenon of store-activated Ca2+ inflow (capacitative Ca2+ entry) in which
      the depletion of Ca2+ in the endoplasmic reticulum (ER) increases the probability
      of opening of store-operated Ca2+ channels (SOCs) located in the plasma membrane
      is ubiquitous in 'non-excitable' animal cells and is also found in some
      'excitable' cells. At present, neither the structures of SOCs nor the
      mechanism(s) by which a decrease in Ca2+ in the lumen of the ER activates SOCs
      are well understood. This paper discusses the hypothesis that a decrease in the
      concentration of Ca2+ in restricted regions of the subplasmalemmal space (bounded
      by the plasma membrane and peripheral regions of the ER) is responsible for the
      activation of SOCs. The hypothesis rests on observations made by others that Ca2+
      is a strong feed-back inhibitor of SOCs and of the endoplasmic reticulum
      (Ca(2+)+Mg2+)-ATPases (SERCAs), and on the concepts (developed previously by
      others) of a subplasmalemmal space and the directed flow of Ca2+ through SOCs
      into the lumen of the ER and from there to the deep cytoplasmic space. The way in
      which the hypothesis might explain the actions of agonists (acting via inositol
      1,4,5-trisphosphate) and thapsigargin (an inhibitor of SERCAs) in activating SOCs
      under physiological conditions is described. The proposed involvement of
      thapsigargin-insensitive SERCAs, and possible limitations of the hypothesis are
      discussed.

PMID- 9570012
TI  - Regulation of gene expression, growth, and cell survival by IL-4: contribution of
      multiple signaling pathways.
AB  - Interleukin-4 is a cytokine produced by activated T cells, mast cells, and
      basophils that elicits many important biological responses[1] (see Tab 1). These
      responses range from the regulation of helper T cell differentiation[2] and the
      production of IgE[3] to the regulation of the adhesive properties of endothelial
      cells via VCAM-1[4]. In keeping with these diverse biological effects, high
      affinity binding sites for IL-4 (Kd 20 to 300 pM) have been detected on many
      hematopoietic and non-hematopoietic cell types at levels ranging from 50 to 5000
      sites per cell[5]. This review will focus on the discrete signal transduction
      pathways activated by the IL-4 receptor and the coordination of these individual
      pathways in the regulation of a final biological outcome.

PMID- 9570013
TI  - The role of the hedgehog/patched signaling pathway in epithelial stem cell
      proliferation: from fly to human.
AB  - The hedgehog-patched (hh-ptc) intercellular signaling pathway has recently been
      shown to control the proliferation of epithelial stem cells in both Drosophila
      and vertebrates. Mutant and ectopic expression analyses in Drosophila suggest
      that the HH protein diffuses from the signaling cells to promote the
      proliferation of nearby ovarian somatic stem cells by antagonizing the
      suppression of its receptor PTC towards the CI transcription factor in the stem
      cells. Consequently, the transcription of CI-dependent genes leads to stem cell
      proliferation. This regulatory pathway appears to function also in vertebrates,
      where defects in ptc cause basal cell carcinoma, tumors of epidermal stem cell
      origin. Basal cell carcinoma can also be induced by ectopic expression of Sonic
      hedgehog (shh) or Gli1, the vertebrate homolog of ci. These studies suggest the
      conservation of the hh signaling pathway in controlling epithelial stem cell
      divisions among different organisms.

PMID- 9570014
TI  - Types of voltage-dependent calcium channels involved in high potassium
      depolarization-induced amylase secretion in the exocrine pancreatic tumour cell
      line AR4-2J.
AB  - In the perifused fura-2 loaded exocrine pancreatic acinar cell line AR4-2J pulses
      of high potassium induced repetitive increases in intracellular calcium. Attached
      cells when stimulated with high potassium secreted large amount of amylase. High
      potassium-induced secretion was dependent both on the concentration of potassium
      and duration of stimulation. High potassium induced increases in intracellular
      calcium were inhibited by voltage-dependent calcium channel antagonists with an
      order of potency as follows: nifedipine > omega-agatoxin IVA > omega-conotoxin
      GVIA. In contrast, the L-type calcium channel antagonist nifedipine almost
      completely inhibited potassium-induced amylase secretion, whereas the N-type
      channel antagonist omega-conotoxin GVIA was without effect. The P-type channel
      antagonist omega-agatoxin IVA had a small inhibitory effect, but this inhibition
      was not significant at the level of amylase secretion. In conclusion, the AR4-2J
      cell line possesses different voltage-dependent calcium channels (L, P, N) with
      the L-type predominantly involved in depolarization induced amylase secretion.

PMID- 9570015
TI  - Trichosanthin inhibits T cell activation by interfering with the recruitment of
      ZAP-70 to CD3 zeta chain.
AB  - Plant protein Trichosanthin (Tk) has been shown in our previous experiments to
      suppress antigenic response of T cells. Here we explored its inhibitory
      mechanisms on the proliferation of human Jurkat leukemia T cell triggered by anti
      CD3 McAb. By examination of tyrosine phosphorylation of cell lysate, we were able
      to show that Tk could interfere with the PTK-related activity in the TCR/CD3
      initiated signal transduction in addition to blocking the phosphorylation of PKC.
      As shown in our experiment, the expression intensity of ZAP-70, a kind of protein
      tyrosine kinase, was not changed but its phosphorylation could be inhibited. When
      physical link between CD3 zeta chain and ZAP-70 was further examined by using
      coimmunoprecipitation after pluse-treatment of the cell line with Tk, the anti
      CD3 McAb-induced recruitment of ZAP-70 to CD3 zeta chain was observed to be
      blocked in some extent. This may account for, at least in part, how Trichosanthin
      was able to inhibit the TCR-triggered T cell proliferation.

PMID- 9570016
TI  - The effect of external Ca2+ and Ca(2+)-channel modulators on red-light-induced
      swelling of protoplasts of Phaseolus radiatus L.
AB  - Red-light-induced swelling of the protoplasts isolated from hypocotyl of
      etiolated mung bean (Phaseolus radiatus L.) was observed only when Ca2+ ions were
      present in the medium. The optimal CaCl2 concentration was 250 microM. Swelling
      response declined when Ca2+ was supplied into the medium after red light
      irradiation. The Ca(2+)-chelator EGTA eliminated the red-light-induced swelling
      and 45Ca2+ accumulation in the protoplasts. In contrast, A23187, a Ca(2+)
      ionophore, could mimic the effect of red light in darkness. These results
      indicate that Ca2+ may play a role in light signal transduction. In addition,
      swelling response was prevented by TFP and CPZ (both are CaM antagonists),
      implying the involvement of CaM in red-light-induced and Ca(2+)-dependent
      protoplast swelling.

PMID- 9570017
TI  - Immunolocalization of actin in intact and DNA- and histone-depleted nuclei and
      chromosomes of allium cepa.
AB  - The presence of actin in eukaryotic nuclei and chromosomes, and especially in
      higher plant nuclei and chromosomes, has not been well established. We detected
      actin in meristematic cells of Allium cepa with indirect immunofluorescence
      technique and observed bright fluorescence in the intact nuclei and chromosomes,
      indicating that actin is present in the nuclei and chromosomes of the higher
      plant. We labeled sections of the meristematic cells of A. cepa with immunogold
      technique, gold particles were found over the whole nuclei and a number of gold
      particles were concentrated in condensed chromatin and nucleoli, confirming the
      results of the immunofluoresence observations. We treated the nuclei and
      chromosomes of A. cepa with DNase I and 2M NaCl and obtained DNA- and histone
      depleted nuclei and chromosomes. Indirect immunofluorescence tests showed that
      the DNA- and histone-depleted nuclei and chromosomes reacted positively with the
      anti-actin antibodies. These results demonstrate that actin exists not only in
      intact nuclei and chromosomes, but also in DNA- and histone-depleted nuclei and
      chromosomes of the plant. In addition, our immuno-fluorescence tests indicate
      that tropomyosin is present in the nuclei and chromosomes of A. cepa.

PMID- 9570018
TI  - EGFR antisense RNA blocks expression of the epidermal growth factor receptor and
      partially reverse the malignant phenotype of human breast cancer MDA-MB-231
      cells.
AB  - The effects of human EGFR to the malignant phenotype of human breast cancer cell
      line MDA-MB-231 were investigated experimentally. A retroviral vector containing
      a 5'1350bp fragment of the human EGFR cDNA in the antisense orientation was
      transfected into targeted cells by lipofectamine. The effects on cell
      proliferation, cell cycle and adherent ability to extracellular matrix (ECM)
      components were studied after the expression of antisense transcripts to EGFR
      5'1350bp fragment in target cells. In vitro studies showed that the growth
      ability of the transfected cells was partially inhibited in comparison to
      parental cells and to cells transfected with the plasmid containing the neomycin
      resistance gene only. It was found that EGF (10 ng/ml) had an argumenation effect
      on the growth of transfected MDA-AS10 cells but not MDA-MB-231 cells. Flow
      cytometric analysis showed that the cell cycle of the transfected cells was
      abnormal with a decrease of cells in G2/M and S phases and an increase of cells
      in G1 phase, indicating a blockage in phase G1. Immunofluorescence of EGFR
      expression in transfectants stained with an anti-EGFR antibody was decreased and
      their growth in soft agarose was also severely impaired. The transfected cells
      showed less adherence to laminin (LN) and fibronectin (FN). In short, EGFR
      antisense RNA decreases the expression of EGFR on MDA-MB-231 cells and partially
      reverses their malignant phenotype as well.

PMID- 9570019
TI  - The use of suicide gene systems in vascular cells in vitro.
AB  - To investigate the efficiency of suicide gene systems on vascular cells, HSV
      tk/GCV and EC-CD/5-FC systems were established on vascular endothelial cells in
      vitro by retroviral transduction. Both modified cell lines were highly sensitive
      to prodrugs, the IC50 for GCV was less than 0.4 microM, and IC50 for 5-FC was
      less than 75 microM, while the parental endothelial cells were insensitive even
      at the highest concentrations of prodrugs in this experiment. Mixed cellular
      assay showed that significant bystander effect was exhibited in modified
      endothelial cells. When only 10% or 30% of the mixed cells were tk positive and
      exposed to 20 microM GCV for 6 days, more than 60% or 90% of the whole population
      was killed. Similar result was also found in CD positive cells. These results
      indicated that both HSV-tk/GCV and EC-CD/5-FC systems could efficiently suppress
      endothelial cell growth in vitro.

PMID- 9570020
TI  - Advantages and disadvantages of neurological scales.
AB  - The neurological features demonstrated by a patient form a valid measurement for
      the level of impairment experienced following a stroke. These features can be
      assessed using neurological scores, which assign values to the many deficits
      exhibited by such patients and allow a prognosis to be made on patient outcome.
      Several stroke scales have been produced, most of which are based on normative
      scaling. While these stroke scales provide effective patient assessment, they do
      have some associated disadvantages. The analysis of multiple minor deficits can
      lead to the same scoring as a few major deficits, some scales assess stroke only
      on a small number of items. In addition, most scales operate best in the middle
      range of stroke severity and have limited value in mild and severe cases. Despite
      these drawbacks, neurological scores give an earlier and more sensitive response
      to the outcome of stroke than functional scales. They are powerful prognostic
      indicators in stroke. Most of them are equivalent, which allows comparison
      between studies.

PMID- 9570021
TI  - Diffusion and perfusion MRI, measurements of acute stroke events and outcome:
      present practice and future hope.
AB  - The morphological, metabolic and functional changes of brain ischaemia can be
      studied using various MRI methods. These are readily available should the early
      visualisation of affected territories be needed. Morphological changes include
      the depiction of oedema on T1- and T2-weighted images, and metabolic changes are
      reflected on magnetic resonance spectroscopy. Functional changes reflect
      haemodynamic failure seen on diffusion- and perfusion-weighted imaging. Modelling
      of behaviour of T2 and diffusion changes could predict the histological outcome
      of affected tissue regarding cell recovery on necrosis. In addition, the
      combination of diffusion and perfusion MRI offers a potential prognostic value.

PMID- 9570022
TI  - Acute stroke subtypes--is there a need for reclassification?
AB  - Although stroke covers a wide range of diseases and aetiologies, it is currently
      managed using uniform treatments, such as thrombolysis and neuroprotective drugs,
      irrespective of the individual stroke pathophysiology. The time-consuming,
      ineffective and often misleading standard work-up of stroke subtypes is now being
      augmented with immediate brain and vessel imaging studies and laboratory testing.
      This approach means that, in addition to distinguishing between haemorrhagic and
      ischaemic lesions, ischaemic lesions can be assigned to various stroke subtypes.
      Diffusion-weighted magnetic resonance imaging is useful to detect the cytotoxic
      oedema occurring early in cerebral ischaemia, and sequential studies are useful
      in evaluating each patient's prognosis. Both this technique and magnetic
      resonance angiography are effective in the assessment of an optimal selection of
      therapy in early stroke. Particular benefit is derived by patients with recent
      infarction and overlapping signs and symptoms of residual and acute deficits, and
      those with more than one aetiology. Demonstration of very small versus large
      ischaemic territories supports the likelihood of a good spontaneous outcome and
      discourages high-risk treatment procedures. Chronic and acute lesions may be
      differentiated and potentially salvageable tissue identified in cases of embolic
      stroke. The micro-embolic nature of lesions formed by the fragmentation of more
      proximal intracranial artery occlusions may be revealed by ultrasound studies
      showing high-intensity transient signals. Results from such studies are also
      useful to re-evaluate present concepts of stroke subtypes: recent data suggest
      that the 'border zone infarction' concept needs to be largely abandoned.

PMID- 9570024
TI  - What questions can large, simple trials answer?
AB  - Large, simple trials can provide reliable evidence on the balance of risk and
      benefit of widely practicable treatments that have moderate effects on major
      clinical outcomes. Treatments for stroke will potentially be used extensively
      world-wide. Each year about 8,000,000 people have an acute stroke, with about
      5,000,000 being ischaemic. Of these, perhaps 1,000,000 receive medical attention
      within the first few hours of stroke onset. If reliable decisions about the
      treatment of such large numbers of patients are to be made, we need to be certain
      about the effects of treatment on death from any cause (and on other important
      outcomes) and in many different types of patient. Generally, such reliable
      evidence on whether to treat and on whom to treat, will only come from large,
      randomised trials recruiting many thousands of patients. Such trials are only
      feasible and affordable if they are simple.

PMID- 9570023
TI  - Quantitative neuroimaging for the evaluation of the effect of stroke treatment.
AB  - A prerequisite for the successful treatment of acute ischaemic stroke is the
      existence of viable tissue that is morphologically intact but functionally
      impaired due to a flow decrease below a certain threshold. At this stage, tissue
      at risk of infarction can be identified only by functional imaging. This
      penumbral tissue can be classified as having a critical flow decrease with
      preservation of oxygen consumption and therefore increased oxygen extraction.
      Such 'misery-perfused' tissue has been observed consistently in the first few
      hours following ischaemic stroke but usually develops into necrosed tissue at
      follow-up observations. Several studies have indicated that penumbral tissue can
      be identified up to 17 h or even 48 h after stroke in the border zones of
      ischaemic tissue and that this condition is occasionally reversible without
      resulting in permanent infarction. Positron emission tomography studies of
      cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and cerebral
      metabolic rate of glucose (CMRglc) can be used to demonstrate the effect of
      treatment on functional variables within tissue showing perfusional disturbances.
      Such studies have shown the value of these markers of ischaemia, which also
      correlate with clinical efficacy. However, when therapeutic strategies, such as
      thrombolysis, do not permit arterial blood sampling, quantitative determinations
      of CBF and CMRO2 are not feasible. In such cases relative indices, such as those
      for CBF, must be applied. Such qualitative assessments of perfusion, which were
      calibrated in an independent cohort of patients with acute stroke, were used to
      demonstrate the effect of early systemic treatment of acute ischaemia with
      recombinant tissue plasminogen activator. By applying operationally defined
      thresholds for tissue viability and the penumbra, and co-registering these tissue
      compartments to infarcted and non-infarcted tissue on late magnetic resonance
      imaging, the proportions of at-risk tissue salvaged from infarction could be
      revealed in individual patients. In the future, functional imaging modalities
      that could eventually include tracers for neuronal integrity could be used to
      select patients for thrombolytic therapy. In some instances such techniques may
      permit the extension of the critical time period for inclusion of patients to
      aggressive stroke management strategies.

PMID- 9570025
TI  - Fetal sex and variations in kinetic properties of neutrophil alkaline phosphatase
      during the second trimester of normal pregnancy.
AB  - A kinetic parameter (the Vm/Km ratio), an index of neutrophil alkaline
      phosphatase catalytic efficiency, was studied in 36 women with normal pregnancies
      at 16-20 weeks' gestation. On each blood sample, determinations were achieved on
      enzyme extracted from maternal granulocytes by monitoring the phosphohydrolytic
      activity at 400 nm on a spectrophotometer equipped with software for computation
      of kinetic parameters. Infant sex was recorded at the delivery for all women
      included in this study. The recent introduction of NAP as a marker for some
      pathological pregnancies requires a better knowledge of the behaviour of that
      enzyme in physiological conditions. Data reported focus attention on fetal sex.
      It appears to be one of the factors involved in variations of kinetic parameters
      observed in maternal NAP. Sex-linked differences in placental maturation could
      explain these results.

PMID- 9570026
TI  - Twinning in Sweden between 1973 and 1990. The recurrence rate.
AB  - AIM: To ascertain the recurrence rate of twinning, by determining the repeat
      frequency in a population-based material of women who have already had one set of
      twins. MATERIAL AND METHODS: All singleton and twin births in Sweden between 1973
      and 1990 were identified from the Medical Birth Registry (MBR), at the National
      Board of Health and Welfare, Stockholm. In the MBR fewer than 1% of all women
      with a singleton birth and fewer than 3% of all women with a twin birth are
      missing. When appropriate, 95% confidence limits (95% CL) were calculated.
      RESULTS: Altogether, 84 women with at least two twin births were identified. When
      the proband twins were like-sexed, the observed/expected ratio was 1.7 (95% CL
      1.3, 2.2). For unlike-sexed proband twin pairs, the corresponding figures were
      3.3 (95% CL 2.3, 4.7). CONCLUSION: For women with one twin birth, the likelihood
      of having twins in a subsequent birth increases two to three-fold.

PMID- 9570027
TI  - Cytological changes in endotracheal aspirates associated with chronic lung
      disease.
AB  - Endotracheal aspirates taken serially from mechanically ventilated premature
      infants born at < 28 weeks gestation between March 1992 and August 1993 were
      studied to determine whether early cytological changes would be a good predictor
      of lung damage in infants who develop chronic lung disease (CLD). CLD was
      diagnosed if the infant required supplemental oxygen at 36 weeks corrected
      gestational age. Fifty-five infants were enrolled in the study, five died and of
      the 50 infants remaining, 17 (34%) developed CLD. The infants with CLD had a
      significantly lower gestation (25.5 +/- 1.8 (mean +/- 1 SD) versus 26.2 +/- 0.9
      weeks, p < 0.05), significantly more required surfactant (14/17 vs. 16/33, p <
      0.05) and were ventilated for a significantly longer period (43.3 +/- 26.6 vs.
      19.3 +/- 12.8 days, p < 0.0001). Endotracheal aspirate cytology showed that
      infants with CLD had significantly more degenerated columnar epithelial cells on
      day 3 (p = 0.001), and more neutrophils on day 10 (p = 0.007). Though not
      predictive of CLD, cytological changes consistent with bronchial epithelial and
      pulmonary damage followed by an inflammatory response were found in the tracheal
      aspirates of a group of infants clinically diagnosed with CLD.

PMID- 9570028
TI  - A developmental study of the dopamine D2R receptors in the human basal ganglia
      and thalamus.
AB  - The development of the dopamine D2R receptors (D2R) in the human basal ganglia
      (BG) and thalamus was investigated in 25 normal brains by means of an
      immunohistochemical method and Western blotting. Immunoreactivity to D2R was
      detected in the cytoplasm and dendrites of small and large neurons in the BG and
      thalamus. D2R-positive neurons were clearly observed at 19 weeks of gestation
      (GW) in the globus pallidus and thalamus, and at 21 GW in the striatum. The
      number of D2R-positive neurons gradually increased and reached a peak at 27 GW in
      the globus pallidus, at 39 GW in the thalamus, and at 1 month of age in the
      striatum. The number of D2R-positive large neurons in the globus pallidus and
      small neurons in the striatum decreased after 1 year and about 10 years of age,
      respectively. Western blotting confirmed the specificity of the
      immunohistochemistry. Our results suggest that the D2R protein begins to be
      synthesized at an early fetal stage in the BG and thalamus, and the development
      of D2R is mostly consistent with neuronal maturation in the BG. D2R may play an
      important role in regulating the neuronal development of the BG. The decrease in
      D2R-positive neurons may be related to D2R post-transcriptional regulation.

PMID- 9570029
TI  - Urinary excretion of aquaporin-2 in term and preterm infants.
AB  - Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel of the renal
      collecting duct and is excreted in human urine. We measured the urinary excretion
      of AQP-2 by radioimmunoassay in 14 term and 12 preterm infants aged 1 month.
      Excretion of AQP-2 was low compared with adults, and correlated significantly
      with urine osmolality in preterm infants. Our results demonstrate that AQP-2
      water channels are expressed in the renal collecting duct of both term and
      preterm infants.

PMID- 9570030
TI  - Fetal growth retardation as a cause of impaired ovarian development.
AB  - Low birthweight has been associated with diseases and disorders later in life. It
      has been suggested that this is caused by the impaired development of abdominal
      organs, especially in cases of growth retardation. Besides general malnutrition
      of the fetus, preferential bloodflow to the heart and brain may further deprive
      organs, such as liver, pancreas and kidney, of nutrients. As a result these
      organs may not develop properly. Anatomically, the ovary is situated close to the
      kidney and it is very likely that, similar to the kidney, ovarian development can
      be negatively affected by intra-uterine growth retardation. Placental
      insufficiency, which is an important cause of severe intra-uterine growth
      retardation, was used as a model to investigate this hypothesis. In the present
      study, the volume percentages of primordial follicles in the ovaries of four
      severely growth-retarded fetuses of different gestational ages are compared to
      those of four age-matched controls. It is found that these volume percentage in
      growth-retarded fetuses were significantly lower than those observed in the age
      matched controls. It can be concluded that ovarian development is impaired in
      intra-uterine growth-retarded fetuses. These findings further suggest that, as a
      result of the premature loss of follicles, females with low birthweights may
      encounter fertility problems later in life.

PMID- 9570031
TI  - Soothing effect of amniotic fluid smell in newborn infants.
AB  - Newborn young of several mammalian species are attracted to the odor of amniotic
      fluid (AF); these chemical cues also appear to calm neonates and help them adapt
      to their novel postnatal environment. AF odor likewise elicits positive (head
      orientation) responses by human infants. The present study systematically
      examined whether the odors of AF and mother's breasts influence the crying of the
      newborn infant, when separated from its mother. The total crying time from 31-90
      min postnatal was registered on tapes in 47 healthy fullterm newborns, allocated
      to one of three conditions; exposure to either AF or breast odor or no exposure
      (controls). Babies exposed to AF smell cried significantly less (median 29 s)
      than babies in the two other groups (breast odor--301 s, controls--135 s). The
      data are consistent with the hypothesis that the fetus may become familiar with
      chemical cues present in the intrauterine environment. Our data provide new
      evidence of the human baby's fine olfactory discrimination capacity, and add to
      the growing body of evidence indicating that naturally occurring odors play an
      important role in the mediation of infants' early behavior.

PMID- 9570032
TI  - Gut hormone levels in neonates under phototherapy.
AB  - Gastrin, vasoactive intestinal peptide (VIP) and neurotensin plasma levels were
      measured in three groups of healthy term newborn infants, on the 3rd, 4th and 5th
      days of life. Group A consisted of 15 babies without jaundice. Group B comprised
      of 15 babies with mild jaundice (bilirubin levels < 256 mumol/l) and group C
      included 15 babies with marked jaundice (bilirubin levels > 256 mumol/l) who
      received phototherapy for at least 24 h. There was no significant difference in
      gut hormone levels between groups A and B. Infants in group C had significantly
      lower gastrin levels compared to infants in groups A and B, on both days 4 and 5.
      VIP levels on the 4th day of life were significantly higher in group C in
      comparison to groups A and B. Neurotensin levels in the three groups did not
      differ significantly. Increased stool number was noted in infants in group C.
      Increased VIP levels in jaundiced infants under phototherapy may be the cause of
      increased stool frequency, through stimulation of intestinal water and
      electrolyte secretion.

PMID- 9570033
TI  - Prenatal development of arm posture.
AB  - Fetal arm posture was studied longitudinally in 10 uncomplicated pregnancies
      using real-time ultrasound. Observation were performed at four weekly intervals
      from 12 to 36 weeks, and at 38 weeks. The percentage of assessments with optimal
      visualization of elbow, wrist and fingers was 84% at 12 weeks and more than 90%
      thereafter (range 92-98%). There was a clear developmental trend towards
      increased flexion. Flexion of the elbow occurred frequently from 12 weeks onwards
      with an increased incidence at 16 weeks, that in the fingers from 20 weeks
      onwards and from 28 weeks to term age in the wrist. All three trends were
      statistically significant. There was considerable intra-individual consistency in
      terms of the ages at which flexion increased. In fact the increase of flexion
      occurred one session later in only 6/30 registrations. The combined data of the
      elbow, wrist and fingers revealed preferential arm posture at 12 weeks with the
      elbow flexed and the wrist and fingers extended. From 16 to 28 weeks, the
      predominant posture consisted of elbow flexion, wrist extension and finger
      flexion and complete flexion thereafter. The development of fetal arm posture
      does not comply with a proximo-distal trend in that there was first an increase
      in flexion at the elbow, followed by the fingers and finally the wrist. The
      implications of our findings for understanding the prenatal development of the
      central nervous system and subsequent postural adjustments to extrauterine life
      are discussed.

PMID- 9570034
TI  - Intraadrenal interactions in the regulation of adrenocortical steroidogenesis.

PMID- 9570035
TI  - The endocrine effects of nonhormonal antineoplastic therapy.

PMID- 9570036
TI  - Endocrinopathies in the family of endoplasmic reticulum (ER) storage diseases:
      disorders of protein trafficking and the role of ER molecular chaperones.
AB  - From the studies described in this review, it is clear that structural
      information dictates not only the functional properties of exportable proteins,
      but also their ability to be transported in the intracellular secretory pathway.
      In ERSDs, the precise nature of the defect determines both the severity of the
      phenotype and the mode of inheritance. To our knowledge, all genetically
      inherited ERSDs are attributable to mutations in the coding sequence of
      exportable proteins; thus far, with the exception of abetalipoproteinemia (see
      Section IV.D), no mutations in ER chaperones (other than those that scientists
      have genetically engineered) have been reported as the cause of spontaneous
      disease. The elevations of ER chaperones in ERSDs may differ between mutations,
      between tissues, between individual patients, and between different physiological
      states (i.e., such as before and after hormone replacement therapy) in the same
      patient. Thus, measurement of ER chaperone levels plays an important diagnostic
      role, but probably should not be used as the sole basis to classify these
      illnesses. Moreover, because mutant secretory proteins have been reported to
      occur in virtually every organ system, ERSDs are more readily classified at the
      cell biological level, by the responses of the cells that actually synthesize the
      secretory protein, rather than the hormone deficiency associated with the illness
      at the end-organ level. With these ideas in mind, we present a schematic view in
      Fig. 4. According to this schema, all ERSDs begin with ER retention of the
      affected proteins or their subunits. Mutants may then be divided into two groups:
      type A, where the biological activity is preserved although the protein is
      transport-deficient; and type B, where the mutant has no potential for functional
      activity. Both categories include both recessive and dominant mutations. The
      primary clinical difference between these two classes is that type A ERSDs may be
      amenable to therapies designed to down-regulate the quality control of ER export
      so that potentially functional molecules can escape the ER and reach their
      intended intracellular destination. In both types of ERSDs, in most cases, the
      retained mutant protein is efficiently degraded in the ER (subtypes A-I and B-I).
      In these cases, the predominant, global phenotypes involve the symptoms and signs
      of hormone deficiency. However, careful biochemical and cell biological studies
      reveal various abnormalities in glandular function, typically including the
      elevation of the levels of one or more ER chaperones. As described in Section
      I.C, such elevations are a consequence of chronic adaptation to the presence of
      unfolded mutant secretory protein (the synthesis of which is stimulated all the
      more by endocrine feedback loops). As described in Section III, the elevated
      chaperones appear to be integrally related to the ER retention as well as perhaps
      the ERAD process that removes the misfolded proteins. In these cases, the ER
      compartment may expand, but the secretory cells are likely to survive. In the
      more unusual subtype II (subtypes B-II and perhaps A-II), the mutant protein
      exhibits an intrinsic tendency to resist ERAD, creating a potentially dangerous
      accumulation of indigestible material (Fig. 4). This may be due to the unusual
      production of novel, protease-resistant protein complexes, or it may be due to
      the formation of protein assemblies that prevent the reverse translocation of
      mutant proteins to the cytosol for proteasomal proteolysis. Resistance of
      untransported mutant protein to ER-associated degradation will predispose to a
      dominant ERSD (460). In such a case, although the mutant allele could could form
      oligomeric hybrids with the wild-type allele, complete nonmixing of the normally
      exported wild-type allele and toxic accumulation of the mutant allele is another
      distinct scenario that can also produce a dominant mode of inheritance. (ABSTRACT
      TRUNCATED)

PMID- 9570037
TI  - The diagnosis of growth hormone deficiency in children and adults.

PMID- 9570038
TI  - CSF-1 and interferon-gamma act synergistically to promote differentiation of FDC
      P1 cells into macrophages.
AB  - FDC-P1 cells expressing the wildtype CSF-1 receptor, FDwtfms, differentiate into
      macrophages during incubation with CSF-1. This response is amplified in the
      presence of interferon-gamma. Cells expressing the 807F mutant receptor, 807F
      cells, proliferate in response to CSF-1 and do not differentiate. However, in
      response to CSF-1 and interferon-gamma they differentiate as well. CSF-1 causes
      the activation of STAT proteins in FDwtfms cells, but not in 807F cells. Cellular
      differentiation correlates with a sustained activation of STAT1 and STAT3 in
      response to interferon-gamma over at least 40 hours. However, interferon-gamma
      alone did not cause differentiation of cells expressing either receptor. Other
      defects in response to CSF-1 of the 807F cells, such as lack of PLC gamma 2
      activation, were not complemented by co-incubation of the cells with CSF-1 and
      interferon-gamma. It appears that a combination of signaling pathways are
      activated by CSF-1 and interferon-gamma which caused the shift of response from
      proliferation to differentiation in the 807F cells and an enhanced
      differentiation in the FDwtfms cells.

PMID- 9570039
TI  - Role of FGF3 in otic capsule chondrogenesis in vitro: an antisense
      oligonucleotide approach.
AB  - Initiation of otic capsule chondrogenesis depends on interactions between the
      otocyst and surrounding periotic mesenchyme. We previously reported localization
      of endogenous basic fibroblast growth factor (FGF2) to the epithelium of the
      mouse otocyst, and initiation of chondrogenesis in cultured periotic mesenchyme
      by this epithelial-derived signaling molecule. We now report that FGF3, related
      to FGF2, can also initiate otic capsule chondrogenesis. We show localization of
      endogenous FGF3 to the otocyst, and suppression of chondrogenesis by antisense
      oligonucleotides complementary to different regions of the murine FGF3 gene. Our
      results support a role for FGF3 in otic capsule formation in situ.

PMID- 9570040
TI  - The in vivo activity of vascular endothelial growth factor isoforms in the avian
      embryo.
AB  - The activity of the different isoforms of quail vascular endothelial growth
      factor (VEGF; 122, 146, 166 and 190 amino acids) were quantitatively examined in
      vivo by overexpression in the chicken embryo using the retroviral expression
      vector RCAS. All isoforms were potent inducers of vascularization and
      permeability. A linear relationship between expression of their mRNA and
      induction of vascularization and permeability was observed for all isoforms.
      Pattern formation and morphogenesis was otherwise not altered. Overexpression of
      qVEGF122 and 146 in the eye of chicken embryos did not induce vascularization of
      either the cornea or retina-which are avascular tissues in birds. We conclude
      that all isoforms of VEGF are potent inducers of angiogenesis dependent on a
      permissive environment.

PMID- 9570041
TI  - Characterization of cell-associated and soluble forms of connective tissue growth
      factor (CTGF) produced by fibroblast cells in vitro.
AB  - Connective tissue growth factor (CTGF) is a mitogenic and chemotactic factor for
      cultured fibroblasts that has been implicated in wound healing, fibrotic
      disorders and uterine function. Although the primary translational products of
      the mouse, human and pig CTGF (mCTGF, hCTGF, pCTGF) genes are predicted to be
      secreted and of approximate M(r) 38,000, 10 kDa biologically active forms of
      pCTGF have recently been described. In this report, we show that human foreskin
      fibroblasts (HFFs) and mouse connective tissue fibroblasts contained 2.4 kb CTGF
      transcripts, stained positively with an anti-CTGF[81-94] peptide antiserum, and
      produced a 38 kDa protein that was immunoprecipitated by an anti-CTGF[247-260]
      peptide antiserum. While 38 kDa CTGF was readily detected in cell lysates, it was
      non- or barely detectable in conditioned medium. 38 kDa CTGF remained cell
      associated for at least 5 days after synthesis and was not releasable by
      treatment of the cells with trypsin, heparin, 1 M NaCl or low pH. Purification of
      CTGF from human or mouse fibroblast conditioned medium resulted in the isolation
      of 10-12 kDa CTGF proteins that were heparin-binding, bioactive, and reactive
      with anti-CTGF[247-260] on Western blots. Whereas 10 kDa CTGF stimulated DNA
      synthesis in 3T3 cells to the same extent as platelet-derived growth factor
      (PDGF)-AA, -AB, or -BB, it did not compete with 125I-PDGF-BB for binding to alpha
      alpha, alpha beta or beta beta PDGF receptors (PDGF-R), did not stimulate
      tyrosine phosphorylation of PDGF-alpha-R or -beta-R, and was not antagonized by a
      neutralizing PDGF-R-alpha antiserum. These data show that, in cultured
      fibroblasts, 38 kDa CTGF is principally cell-associated whereas low mass forms of
      CTGF are soluble and biologically active. They further demonstrate that, contrary
      to the previously proposed properties of 38 kDa CTGF, 10 kDa CTGF does not bind
      to PDGF-R and stimulates Balb/c 3T3 cell mitosis via a PDGF-R-independent
      mechanism.

PMID- 9570042
TI  - Purification and characterization of a recombinant human cripto-1 protein.
AB  - Cripto-1 (CR-1) is a novel protein that contains a modified EGF-like motif and
      that does not directly bind to any of the known erb B type-1 receptor tyrosine
      kinase receptors. To more clearly define the biological effects of CR-1 and to
      more adequately compare the structure-function relationships of CR-1 with other
      members of the EGF family of growth factors, we have expressed a modified, full
      length recombinant human CR-1 protein (rhCR-1) in E. coli and have devised a
      procedure for the solubilization, refolding and purification of a biologically
      active form of this protein. We have generated the mature form of hCR-1 from
      computer assisted predictions of potential signal peptide cleavage sites.
      Expression of the modified rhCR-1 protein in E. coli was limited to the inclusion
      bodies. The rhCR-1 protein was found to be expressed at high levels in bacterial
      cells when fused to a histidine-tag sequence. Refolding of rhCR-1 was found to be
      difficult because of the large number of cysteine residues in the protein which
      results in protein aggregation. By chemically modifying the cysteine residues in
      the rhCR-1 protein with 3-trimethylammoniopropyl methanethiosulfonate, additional
      positive charges have been introduced into the protein by this disulfiding
      reagent. This modification facilitates solubilization of the protein when rhCR-1
      is denatured. The solubilized, denatured protein was then purified by CM cation
      exchange and C4 reverse phase HPLC chromatography and refolded in a redox buffer.
      The refolded, modified rhCR-1 protein was found to be biologically active by its
      ability to inhibit beta-casein expression, to stimulate the tyrosine
      phosphorylation of Shc and the activation of MAPK and by its capacity to
      facilitate branching growth of mouse mammary epithelial cells in type I collagen
      gels.

PMID- 9570043
TI  - Mutational analysis of a transforming growth factor-beta receptor binding site.
AB  - Transforming growth factor-beta s (TGF-beta 1, -beta 2, -beta 3) are important
      regulators of cell growth and differentiation which share approximately 70%
      identical amino acids. Using LS513 colorectal cells, which are growth inhibited
      by TGF-beta 1 (ED50 of 100 pM), but are refractory to TGF-beta 2 (ED50 of 50,000
      to 100,000 pM), we have determined that amino acids 92-98 of TGF-beta specify
      growth inhibition. The chimeric protein TGF-beta 1/beta 2(92-98), in which amino
      acids 92-98 of TGF-beta 1 were exchanged for the corresponding amino acids of TGF
      beta 2, was indistinguishable from TGF-beta 2 at inhibiting growth of LS513
      cells. In contrast, both TGF-beta 1/beta 2(92-95) and TGF-beta 1/beta 2(94-98)
      inhibited the growth of LS513 cells with an ED50 of approximately 1000 pM. TGF
      beta 1/beta 2(95-98), in which amino acids 95-98 of TGF-beta 1 have been replaced
      with the corresponding amino acids of TGF-beta 2, had full activity and was
      indistinguishable from TGF-beta 1. Receptor cross-linking experiments
      demonstrated that binding of the chimeras to the type I and type II receptors of
      LS513 cells was consistent with their biological activity. TGF-beta 1/beta 2(95
      98), TGF-beta 1/beta 2(92-95) and TGF-beta 1/beta 2(94-98) were each similar to
      TGF-beta 2 in that they failed to bind to the soluble Type II receptor in a solid
      phase assay. These results demonstrate that amino acids 92-98 are involved in the
      interaction between TGF-beta and its signaling receptors and they show that
      modest changes within this region can substantially alter biological response.

PMID- 9570044
TI  - The early management of meningococcal disease.
AB  - Meningococcal disease is a fulminant infection with an overall mortality of 8%.
      Mortality is significantly increased with meningococcal septicaemia, particularly
      when there has been a delay in the diagnosis. The trend from 1985 to 1995 has
      been an increase in incidence of this disease, and the relative importance of
      meningococcal disease has also increased following a fall in the incidence of
      invasive Haemophilus influenzae disease with childhood immunisation. The
      management of such cases can be complex and time critical. Patients with
      meningococcal septicaemia often require aggressive resuscitation, including
      airway support, intravenous colloid, and parenteral antibiotics; hypoglycaemia is
      also commonly seen, and inotropes may be needed to support the circulation. We
      examine the treatment strategies in the early management of meningococcal disease
      and provide an algorithm for use by ambulance personnel, general practitioners,
      accident and emergency clinicians, and paediatricians. The objective of this
      algorithm is to ensure that an optimally resuscitated patient is delivered to the
      definitive care facility.

PMID- 9570045
TI  - The cost of alternative models of care for primary care patients attending
      accident and emergency departments: a systematic review.

PMID- 9570046
TI  - The management of minor traumatic brain injury.
AB  - Minor traumatic brain injury accounts for the majority of the one million head
      trauma attendances at A&E departments in the United Kingdom. Guidelines have been
      established listing criteria for skull films, admission to hospital, computed
      tomography, and neurosurgical consultation. These are currently undergoing
      revision and were the subject of a satellite symposium to the J Douglas Miller
      memorial meeting held in October 1996 in Edinburgh. In the East Anglia Region the
      current guidelines have been issued as memo-cards for A&E officers. The aim of
      admission is to observe for deterioration, predominantly caused by intracranial
      haematomas. The indicators for the development of such lesions are an impaired
      level of consciousness and presence of a skull fracture. Such patients should
      therefore undergo regular and frequent neurological observations, and be admitted
      for at least 12 hours. Following discharge, routine follow up should be
      considered to identify and treat patients with postconcussion symptoms and signs.
      The possible way forward for the management of these patients is adopting a
      greater emphasis on preventative aspects, and establishing, implementing, and
      auditing evidence based guidelines. Improved teaching in the form of formal
      induction seminars and computerised teaching aids is required, and a better
      understanding of the aetiology and treatment of the postconcussion syndrome.

PMID- 9570048
TI  - Guidelines for the management of anaphylaxis in the emergency department.
AB  - An algorithm for the emergency treatment of anaphylaxis is presented. The need
      for early hands-on involvement of senior personnel is stressed. Continuous
      assessment, monitoring of response to treatment, and a low threshold for hospital
      admission for observation and further treatment if necessary are required.

PMID- 9570047
TI  - Therapeutic controversies in the management of acute anaphylaxis.

PMID- 9570049
TI  - Effects on patient care of introducing prehospital intravenous nalbuphine
      hydrochloride.
AB  - OBJECTIVE: Since March 1992, intravenous nalbuphine hydrochloride has been used
      prehospital by paramedics in the Plymouth area. This study assesses the impact of
      this intervention. METHODS: A prospective study of the parenteral analgesic
      requirements of 1000 consecutive patients arriving by ambulance at the accident
      and emergency (A&E) department of a large district general hospital. Where
      parenteral analgesia was given in the A&E department but not by ambulance
      personnel, a questionnaire was sent to the ambulance crew concerned to ascertain
      the reasons for not having given nalbuphine. RESULTS: Of 1000 consecutive
      patients arriving by ambulance, 87 (8.7%) had been given parenteral analgesia
      either prehospital, in A&E, or in both places. Seventy five (7.5%) needed
      parenteral analgesia in the A&E department, 29 (2.9%) had been given prehospital
      intravenous analgesia by paramedics, and a further seven (0.7%) had been given
      parenteral analgesia by a general practitioner (GP). Thus 36 (3.6%) received
      prehospital analgesia. Ten patients who had been given analgesia by paramedics
      required no further analgesia in A&E, whereas 51 patients who had not been given
      prehospital analgesia required parenteral analgesia in the A&E department.
      CONCLUSIONS: The introduction of nalbuphine for use by paramedics in prehospital
      care has increased prehospital parenteral analgesia from 1% in 1992 (given by GPs
      only) to 3.6% in the current study group, and 41% of patients requiring
      parenteral analgesia received analgesia prehospital. There may be further scope
      for extending the indications for nalbuphine use by ambulance personnel.

PMID- 9570050
TI  - Notification of infectious diseases by junior doctors in accident and emergency
      departments.
AB  - OBJECTIVE: To assess the knowledge about notifiable infectious diseases by
      accident and emergency (A&E) senior house officers. METHODS: A telephone
      questionnaire of senior house officers was carried out over a one week period at
      the end of their six month attachment in A&E departments in Northern Ireland.
      RESULTS: 81 (91%) of the senior house officers participated in the study; 23
      (29%) realised that the doctor diagnosing the notifiable disease had a statutory
      duty to notify that disease; nine (11%) were aware there were three statutory
      lists in the United Kingdom. Knowledge about which infectious diseases require
      notification varied from 79/81 (98%) for meningococcal disease to 15/91 (19%) for
      methicillin resistant S aureus. Seventy nine (98%) of the doctors thought that a
      poster displayed in the A&E department would be helpful. There was no significant
      difference between duration of qualification and performance on the questionnaire
      (p = 0.2). CONCLUSIONS: Despite varying experience, junior doctors in A&E do not
      know which infectious diseases are notifiable by statute. They felt that it would
      be helpful to have a poster in the A&E department listing the notifiable diseases
      of that region. To encourage accurate reporting, interregional variation between
      the statutory lists should be abolished and replaced by one nationally agreed
      list.

PMID- 9570051
TI  - Can accident and emergency nurse practitioners interpret radiographs? A
      multicentre study.
AB  - OBJECTIVE: To assess the ability of nurse practitioners in accident and emergency
      (A&E) to interpret distal limb radiographs, by comparison with senior house
      officers. DESIGN: Nurse practitioners and senior house officers in 13 A&E
      departments or minor injury units were shown 20 radiographs of distal limbs, with
      brief history and examination findings, and asked to record their interpretation.
      OUTCOME MEASURE: A total score for each subject was calculated by comparing
      answers against agreed correct responses. RESULTS: Nurse practitioners in general
      compared favourably with senior house officers. Those nurse practitioners who
      interpret radiographs as part of their role in minor injury units performed as
      well as the experienced senior house officer group. CONCLUSIONS: Nurse
      practitioners in A&E are able to interpret radiographs to a standard equal to
      senior house officers with three to five months' experience. Those nurse
      practitioners actively interpreting radiographs as part of their role in minor
      injury units are able to interpret radiographs to the same standard as senior
      house officers with more than five months' experience.

PMID- 9570052
TI  - Use of the spinal board within the accident and emergency department.
AB  - A postal questionnaire was sent to all consultants and specialist trainees in the
      West Midlands about the use of spinal boards in the accident and emergency (A&E)
      department. Response rate was 70%. There was widespread use of boards in A&E
      despite an ATLS recommendation to the contrary. Hospitals should review their
      policies on use of spinal boards within the department, using the evidence
      available to determine the best means of immobilisation.

PMID- 9570053
TI  - Relatives in the resuscitation room: their point of view.
AB  - OBJECTIVE: To investigate whether bereaved next of kin would like to have been
      present in the resuscitation room during attempted cardiopulmonary resuscitation
      of their relative, and their experience or knowledge of what is involved in
      cardiopulmonary resuscitation. METHODS: The next of kin of patients who had
      recently died after unsuccessful cardiopulmonary resuscitation in the accident
      and emergency department were contacted initially by telephone and then sent a
      postal questionnaire. RESULTS: Four (11%) of 35 respondents had been asked
      whether they wished to be present in the resuscitation room; 24 (69%) would like
      to have been offered the opportunity, even though not all would have accepted.
      The respondents had a wide variety of perceptions of what happens during
      resuscitation, few of which corresponded to clinical practice. CONCLUSIONS: Most
      relatives of patients requiring cardiopulmonary resuscitation would like to be
      offered the possibility of being in the resuscitation room; this could have
      several benefits.

PMID- 9570054
TI  - Tick bite anaphylaxis in Australia.
AB  - Tick bite anaphylaxis has rarely been reported. It may follow the bite of any of
      the different tick life cycle forms, is related to the release of salivary
      juices, and may range from mild itch to severe wheeze or shock. Data obtained
      suggest that it is more common and potentially life threatening than tick
      paralysis, which is more widely reported. Emergency physicians should recognise
      this possibility following a tick bite and be prepared to give treatment such as
      adrenaline rapidly. Patients should be referred to an allergist after recovery.

PMID- 9570055
TI  - Adult supraglottitis: an important cause of airway obstruction.
AB  - Supraglottitis in the adult can progress rapidly to complete airway obstruction.
      Successful management requires a high index of clinical suspicion at initial
      presentation and anticipation of a fulminant course. All cases should be assessed
      in a resuscitation area by senior medical staff.

PMID- 9570056
TI  - Breaking the rules! Cardiac injury from remote entry sites.
AB  - An unusual case of penetrating injury to the heart is reported. This presented
      late, after an initial silent period. A high index of suspicion must be
      maintained when chest injuries are managed conservatively. If there is doubt, a
      subxiphoid pericardial window may allow cardiac injury to be excluded.

PMID- 9570057
TI  - Conservative management of gastric rupture following scuba diving.
AB  - Gastric rupture is an uncommon surgical problem which normally presents with an
      acute abdomen and peritonism. An unusual case following underwater ascent and its
      conservative management is presented.

PMID- 9570058
TI  - Fibular fracture: detection with high resolution diagnostic ultrasound.

PMID- 9570059
TI  - The treatment of head injury during the Renaissance.

PMID- 9570060
TI  - How to organise a higher training programme in A&E.

PMID- 9570061
TI  - Development of tension pneumothorax after chest drain insertion.

PMID- 9570062
TI  - Measurement of pain in children in the emergency department.

PMID- 9570063
TI  - Healing of large (2 mm) gaps around calcium phosphate-coated bone implants: a
      study in goats with a follow-up of 6 months.
AB  - Plasma-sprayed hydroxylapatite (HA) coatings are known for their ability to
      demonstrate osseointegration with bone. Recently it was found that the amount of
      bone apposition was strongly reduced 6 weeks after implantation in a goat model
      if gaps of two millimeters between bone and apatite coating existed. Stability of
      the apatite coatings examined did not influence the gap-healing ability. This
      study investigated whether a longer follow-up period of 24 weeks would be
      sufficient for the restoration of bone apposition on apatite coatings in an
      identical surgical model with 2 mm gaps, and whether bone apposition on the
      apatite coatings is influenced by the coating stability. Three coatings were
      investigated: 25-30% crystalline HA (aHA), 60-63% crystalline HA (cHA), and 85
      90% crystalline fluorapatite (FA). Uncoated Ti-6A1-4V implants were used as
      controls. Implants were inserted in the femoral condyles of both femora of eight
      goats. Each goat received four implants. Histology revealed that bone formation
      on each of the apatite coatings remained low and did not increase with an
      extended follow-up period of 24 weeks. The coatings showed significantly (P <
      0.01) more bone contact than the uncoated control implants. The three different
      coatings did not show significant differences in bone apposition. The aHA coating
      in most cases had disappeared completely after 24 weeks. Despite the
      disappearance of the aHA coating, bone contact was seen on the substrate surface
      without fibrous tissue interposition. The cHA coating showed minor signs of
      degradation while the FA coatings showed no visible degradation. It is concluded
      that non-press-fit implantation of apatite-coated implants leads to more bone
      apposition as compared to uncoated Ti-6A1-4V implants. However, it is suggested
      by these results that the upper limit of gaps around apatite implants is 2
      millimeters in a non-weight-bearing model in goats. Bone apposition will not
      increase by extending the follow-up period more than six weeks, nor will it be
      altering the stability of the apatite coatings used.

PMID- 9570064
TI  - Shape and orientation of osteoblast-like cells (Saos-2) are influenced by
      collagen fibers in xenogenic bone biomaterial.
AB  - The surface topography of a substratum has been shown to influence the growth and
      morphology of cells in culture. In this study, human osteoblast-like cells (Saos
      2) were cultured on two types of xenogenic biomaterials obtained from bovine
      bone. Both biomaterials were similar in architectural organization and surface
      topography, but they differed in matrix components. The first one was
      characterized by preservation of the mineralized collagen matrix, and the second
      by complete deproteinization which only preserved the mineral phase. Cells
      cultured at the surface of both biomaterials were observed using scanning
      electron microscopy. The beta 1-integrin subunit, known to bind cell and
      collagen, is the major integrin of the osteoblast. It was localized using
      immunogold in transmission electron microscopy. At the surface of the collagen
      containing matrix, cells exhibited an elongated shape and oriented axis parallel
      to the underlying collagen bundles. The beta 1-integrin subunit was localized at
      the outer surface of cells, in close association with collagen and at the contact
      points between cells and biomaterials. In contrast, at the surface of the single
      mineral matrix, cells were round shaped with random disposition. Gold particles
      were found around the cells with no specific relation to the biomaterial. These
      results strongly suggest that the chemical nature of the surface of a bone
      biomaterial directly influences adhesion process, shape, and spatial organization
      of cultured osteoblastic cells.

PMID- 9570065
TI  - A study on the grafting reaction of isocyanates with hydroxyapatite particles.
AB  - The surface grafting reactions of a series of isocyanates with hydroxyapatite
      particles at different temperatures were studied by Infrared spectrophotometry
      (IR) and thermal gravimetric analysis (TGA). The study results show that both
      hexamethylene diisocyanate (HMDI) and isocyanatoethyl methacrylate (ICEM) react
      readily with HA while ethyl isocyanate acetate (EIA) and butyl isocyanate (BIC)
      have lower reactivity towards HA particles. It also has been found that the
      reaction of ICEM with HA follows a second-order reaction mechanism, despite the
      heterogeneous nature of the reaction, while the reaction of HMDI with HA does not
      due to the complexity of the reaction. Based on this study, it is concluded that
      ICEM and HMDI are suitable agents for the coupling of polymers due to their
      reactivity towards HA.

PMID- 9570066
TI  - Possible role of alpha-1-microglobulin in mediating bacterial attachment to model
      surfaces.
AB  - Urine proteins in the molecular weight range of 9-137 kDa deposit to an equal
      extent from pooled human urine onto glass (12.7 +/- 1.9 micrograms/cm) and
      polystyrene (11.8 +/- 1.8 micrograms/cm). Selective desorption of the proteins
      was achieved by washing with water or water/isopropanol mixtures. Irrespective of
      the washing process, proteins of molecular weight greater than 90 kDa remained
      associated with both surfaces while water washings alone removed most low
      molecular weight material. A 29 kDa protein, alpha-1-microglobulin, was removed
      from glass by water washing but required a 30% (v/v) isopropanol wash to desorb
      from polystyrene, implying attachment via hydrophobic bonding. The adhesion to
      polystyrene surfaces of Pseudomonas aeruginosa B4, a clinical isolate from a
      urinary tract infection (UTI), was strongly associated with the presence of alpha
      1-microglobulin, which may be acting as a mediator of bacterial adhesion.

PMID- 9570067
TI  - Design and function of novel osteoblast-adhesive peptides for chemical
      modification of biomaterials.
AB  - Proactive, "next generation" dental/orthopedic biomaterials must be designed
      rationally to elicit specific, timely, and desirable responses from surrounding
      cells/tissues; for example, such biomaterials should support and enhance
      osteoblast adhesion (a crucial function for anchorage-dependent cells). In the
      past, integrin-binding peptides have been immobilized on substrates to partially
      control osteoblast adhesion; the present study focused on the design, synthesis,
      and bioactivity of the novel peptide sequence Lys-Arg-Ser-Arg that selectively
      enhances heparan sulfate-mediated osteoblast adhesion mechanisms. Osteoblast, but
      not endothelial cell or fibroblast, adhesion was enhanced significantly (p <
      0.05) on substrates modified with Lys-Arg-Ser-Arg peptides, indicating that these
      peptides may be osteoblast- or bone cell specific. Blocking osteoblast cell
      membrane receptors with various concentrations of soluble Arg-Gly-Asp-Ser
      peptides did not inhibit subsequent cell adhesion on substrates modified with Lys
      Arg-Ser-Arg peptides, providing evidence that osteoblasts interact with Arg-Gly
      Asp-Ser and with Lys-Arg-Ser-Arg peptides via distinct (i.e., integrin- and
      proteoglycan-mediated) mechanisms, each uniquely necessary for osteoblast
      adhesion. The present study constitutes an example of rational design/selection
      of bioactive peptides, confirms that osteoblast adhesion to substrates can be
      controlled selectively and significantly by immobilized peptides, and elucidates
      criteria and strategies for the design of proactive dental/orthopedic implant
      biomaterials.

PMID- 9570068
TI  - Comparison of the effects of gamma radiation and low temperature hydrogen
      peroxide gas plasma sterilization on the molecular structure, fatigue resistance,
      and wear behavior of UHMWPE.
AB  - The effects of gamma radiation and low temperature hydrogen peroxide gas plasma
      (HPGP) sterilization on structure and cyclic mechanical properties were examined
      for orthopedic grade ultra-high-molecular-weight polyethylene (UHMWPE) and
      compared to each other as well as to no sterilization (control). Density was
      monitored with a density gradient column and was found to be directly influenced
      by the sterilization method employed: Gamma radiation led to an increase, while
      plasma did not. Oxidation of the polymer was studied by observing changes in the
      carbonyl peak with Fourier transform infrared spectrometry and was found to be
      strongly affected by both gamma radiation and subsequent aging, while plasma
      sterilization had little effect. Gamma radiation resulted in embrittlement of the
      polymer and a decreased resistance to fatigue crack propagation. This mechanical
      degradation was a direct consequence of postradiation oxidation and molecular
      evolution of the polymer and was not observed in the plasma-sterilized polymer.
      Both gamma radiation and plasma sterilization led to improved wear performance of
      the UHMWPE compared to the nonsterile control material.

PMID- 9570069
TI  - Use of a diffusion model for assessing the performance of poly(vinyl alcohol)
      bioartificial pancreases.
AB  - Islets of Langerhans surrounded by a semipermeable membrane to prevent an immune
      response by the host immunosystem is a potential way of treating type I diabetes
      mellitus. In this study, poly(vinyl alcohol) (PVA) tubular membranes with added
      polyethylene glycol to create pores in the skin layer were prepared to improve
      their diffusion property. In a static incubation study, islets cultured in the
      PVA tubular membranes still demonstrated their function of secreting insulin
      after 30 days. When the tubular PVA bioartificial pancreas was perifused in a
      small chamber with RPMI-1640 medium containing glucose at concentrations of 5.6
      16.6 mmol/L, insulin release began to increase without delay. Therefore, such a
      membrane is an alternative potential material for a bioartificial pancreas. In
      addition, a mathematical mass transfer model of insulin release was developed and
      compared with the perifusion data. It was shown that satisfactory kinetics could
      be achieved with a PVA membrane. However, the model showed that the insulin
      output of islets cultured in the PVA tubular membrane must be increased to
      improve the performance significantly. These findings suggest that a
      bioartificial pancreas using a PVA membrane is a promising material, but the
      technique for seeding islets in the chamber requires further modification.

PMID- 9570070
TI  - Three-dimensional extracellular matrix engineering in the nervous system.
AB  - Growing neurites are guided through their environment during development and
      regeneration via different cellular and extracellular matrix (ECM) molecular
      cues. To mimic cell-matrix interactions, a three-dimensional (3D) hydrogel-based
      ECM equivalent containing a covalently immobilized laminin oligopeptide sequence
      was designed to facilitate nerve regeneration. This study illustrates that the
      oligopeptide domain CDPGYIGSR covalently linked to an agarose gel as a
      bioartificial 3D substrate successfully supports neurite outgrowth from dorsal
      root ganglia (DRG) in vitro. The specificity of the neurite promoting activity
      was illustrated through the inhibition of neurite outgrowth from DRG in a
      CDPGYIGSR-derivatized gel in the presence of solubilized CDPGYIGSR peptide. Gels
      derivatized with CDPGYIGSK and CDPGRGSYI peptides stimulated a smaller increase
      of neurite outgrowth. In vivo experiments revealed the capability of a CDPGYIGSR
      derivatized gel to enhance nerve regeneration in a transected rat dorsal root
      model compared to an underivatized gel, a CDPGRGSYI gel, and saline-filled nerve
      guidance channels. These data suggest the feasibility of a 3D hydrogel-based ECM
      equivalent capable of enhancing neurite outgrowth in vitro and in vivo.

PMID- 9570071
TI  - Behavior of CHO cells on phosphated cellulose membranes.
AB  - Phosphate groups (negatively charged chemical groups) were grafted onto the
      surface of cellulose membranes by a reaction between hydroxyl groups of cellulose
      and phosphorus pentoxide to observe the effect of phosphate groups on cellular
      behavior. X-ray photoelectron spectroscopy (XPS) was used to determine
      phosphorylation. Captive bubble contact angle measurement was used to determine
      surface wettability. XPS was also used to analyze serum protein adsorption.
      Chinese hamster ovary (CHO) cells were maintained in Ham's F-12 nutrient mixture
      with and without fetal calf serum. Total cell area and shape factor were analyzed
      using image-analyzing software. Serum proteins showed higher adsorption on
      phosphated cellulose. Cell spreading on phosphated membranes was greater than on
      the cellulose membrane that served as control. The cell growth rate was faster
      compared to the control. Large cell aggregates were not found on the phosphated
      membranes, in contrast to the control membrane. The cells on the control were
      aggregated regardless of the existence of divalent cations in the medium.

PMID- 9570072
TI  - Studies on diffusion maximum in x-ray diffraction patterns of plasma-sprayed
      hydroxyapatite coatings.
AB  - Study of an amorphous phase in plasma-sprayed hydroxyapatite (HA) coatings is
      important owing to its unique characteristics and nonnegligible amount of the
      amorphous phase compared to crystalline HA. However, little is known about the
      component parts of an amorphous phase. It is known that amorphous phase usually
      appears as the diffusion maximum (Dmax) in X-ray diffraction (XRD) patterns.
      Analyzing Dmax, including the position (Pmax) and area of Dmax, we can indicate
      the component parts of an amorphous phase and their transitions. In this study,
      the variation of Dmax in XRD patterns of the coatings during plasma spraying, in
      postheating, and in dissolving in vitro was studied with the aid of XRD. It was
      found that component parts of the amorphous phase in the coating varied with
      increasing thickness, consisting of two part represented by Dmax1, located
      between 29.4 and 29.8 degrees (2 theta), and Dmax2, located between 31.0 and 31.4
      degrees (2 theta). It was concluded that Dmax3, located between 32.0 and 32.4
      degrees (2 theta), should be referred to as nanocrystals of HA. In addition, the
      particle size of the starting powder may affect the component parts of the
      amorphous phase in the coating in addition to thickness. With vacuum heating (650
      degrees C) and water vapor treatment at a low temperature (125 degrees C) in a
      saturated vaporic atmosphere, transition of the amorphous components was not as
      efficient as that at 490 degrees C with water vapor. The reason might be that the
      amorphous-to-crystalline HA conversion is dependent on both temperature and water
      vapor pressure. It was found that amorphous components were transformed
      completely into crystalline HA after heating at 490 degrees C with a partial
      water vapor pressure of 0.01 MPa for 2 h. It was concluded that the unstable
      amorphous components (Dmax1, Dmax2) converted into more stable nanocrystals of HA
      (Dmax3). Degradation in vitro showed that Dmax3 was more stable than Dmax1 and
      Dmax2. It was concluded that nucleation of apatite in vitro should be attributed
      to nanocrystals of HA (Dmax3) except for the amorphous components. It is
      recommended that the optimal phasic contents of the plasma-sprayed HA coating be
      mainly composed of crystalline HA and nanocrystals of HA (Dmax3) in terms of the
      stability and biocompatibility of the coating.

PMID- 9570073
TI  - Comparison of the boundary-lubricating ability of bovine synovial fluid,
      lubricin, and Healon.
AB  - Purified human umbilical hyaluronate and a commercial preparation of rooster comb
      hyaluronate (Healon) intended for intra-articular viscosupplementation did not
      demonstrate the same degree of boundary-lubricating ability as bovine synovial
      fluid or its purified lubricating mucin, lubricin (p < 0.01). Boundary
      lubrication was measured in vitro in an arthrotripsometer oscillating natural
      latex against polished glass under a load of 0.35 MPa with an entraining velocity
      of 0.37 mm/s. The two hyaluronate solutions possessed the same hyaluronate
      concentration as synovial fluid, but Healon was 4.5 times more viscous. Present
      practice of viscosupplementation therapy for degenerative joint disease is
      limited and fails to implicate the important role of synovial mucin. Boundary
      lubrication provided by synovial mucin, independent of its viscosity, is not
      replicated by hyaluronate hydrogels.

PMID- 9570074
TI  - Inducible nitric oxide synthase messenger RNA levels in hip periprosthetic
      tissue: a preliminary study.
AB  - Nitric oxide (NO) is a ubiquitous molecule that has been associated with
      inflammation, arthritis, autoimmune disease, bone resorption, and other
      biological processes. Elucidating the role of NO at the bone-implant interface
      may further our understanding of the biological processes of osseointegration,
      loosening, and osteolysis. This study demonstrates the use of a molecular
      biological technique to investigate the possible role of NO in prosthetic
      loosening and periprosthetic bone resorption following total hip arthroplasty.
      Periprosthetic tissue from 12 patients undergoing revision hip arthroplasty was
      harvested and total ribonucleic acid (RNA) was extracted. In six of the 12
      patients, multiple samples from different anatomic locations along the same
      interface were studied. To estimate the amount of NO present in the tissues in
      vivo, the level of inducible NO synthase (iNOS) messenger RNA (mRNA) was
      determined using a ribonuclease (RNase) protection assay. Inducible NOS mRNA was
      detected in every tissue sample: there was no correlation between iNOS mRNA
      levels and clinical loosening or osteolysis. Analysis of multiple tissue samples
      from the same prosthetic component revealed that the levels of iNOS mRNA vary
      greatly, confirming the heterogeneous nature of the interface.

PMID- 9570075
TI  - Scanning electron microscopic, transmission electron microscopic, and confocal
      laser scanning microscopic observation of fibroblasts cultured on microgrooved
      surfaces of bulk titanium substrata.
AB  - During this study, microtechnology and plasma etching were used to produce
      gratings 1.0 (TiD01), 2.0 (TiD02), 5.0 (TiD05), and 10.0 microns wide (TiD10)
      into commercially pure titanium wafers. After incubation of rat dermal fibroblast
      (RDFs) on these surfaces for 3 days, the cells were observed with scanning
      electron (SEM), transmission electron (TEM), and confocal laser scanning
      microscopy (CLSM). Results showed that the RDFs as a whole and their stress
      fibers oriented strictly parallel to the surface pattern on the TiD01 and TiD02
      surfaces. On the TiD05 and TiD10 surfaces, this orientation was not observed. In
      addition, TEM and CLSM demonstrated that the focal adhesion points (FAP) were
      located mainly on the surface pattern ridges. TEM revealed that FAP were wrapped
      occasionally around the edges of the ridges. Only the RDFs on both the TiD05 and
      TiD10 surfaces protruded into the grooves and possessed FAP on the walls of the
      grooves. Attachment to the groove floor was observed only on the TiD10 textures.
      Comparison of these results with earlier observations on microtextured silicone
      rubber substrata suggests that material-specific properties do not influence the
      orientational effect of the surface texture on the observed RDF cellular
      behavior. The proliferation rate of the RDFs, however, seems to be much higher on
      titanium than on silicone rubber substrata.

PMID- 9570076
TI  - Changes in serum conditioning profiles of glutaraldehyde-crosslinked collagen
      sponges after their treatment with calcification inhibitors.
AB  - The purpose of this study was to evaluate the effects of the calcification
      inhibitors FeCl3 and sodium dodecyl sulfate (SDS) on the morphology of
      glutaraldehyde-crosslinked type I collagen sponges and on their serum
      conditioning. Scanning electron microscopy (SEM) showed that the morphology of
      the sponges, already modified by glutaraldehyde crosslinking, underwent further
      changes after treatment of the hydrogels with inhibitors. Coral-like structures
      were found to branch from the bulk of the material especially in the case of SDS
      treated samples. The composition and morphology of the conditioning layers was
      characterized after 48 h incubation in serum by SDS-polyacrylamide gel
      electrophoresis-immunoblot of the adsorbed proteins, by energy-dispersive X-ray
      analysis of the elements (EDX), and by SEM of the conditioned surfaces. All the
      samples showed the adsorption of proteins with molecular weights ranging from 10
      to 203 kD. However, the peculiar adsorption of an approximately 10-kD band
      (complement C3 fragment) and of fibronectin were detected in the case of
      glutaraldehyde-crosslinked collagen. On the other hand, glutaraldehyde
      crosslinked collagen treated with 0.1M FeCl3 showed the remarkable adsorption of
      a 29-kD band. The glutaraldehyde-crosslinked hydrogels showed the massive
      precipitation of crystals on their exposed surfaces, whereas a disordered network
      structure surrounding the collagen fibrils was found in the case of the samples
      pretreated with inhibitors. A predominant precipitation of sodium and chloride
      was detected in all the sponges, although the ratio between the peaks changed
      from from one hydrogel to another. The results reported in this article clearly
      indicate that the treatments with SDS and FeCl3 change the surface conditioning
      of collagen sponges, suggesting a possible role of deposited serum solutes in
      affecting mineralization processes on bioprosthesis.

PMID- 9570077
TI  - Quantification and localization of hyaluronan in a PTFE polymer implanted in the
      corneal stroma.
AB  - The amount and distribution of hyaluronan in a PTFE polymer used to support an
      artificial cornea implanted in the rabbit cornea were determined. The findings
      were used to describe the polymer-corneal stroma interface and the reason for the
      translucence and wettability of this originally opaque and hydrophobic
      biomaterial. PTFE disks (6 mm in diameter, 0.2 mm thick, 50 microns in pore size)
      were implanted after a free-hand intralamellar dissection. The corneas were
      removed 15 days, 1 month, and 3 months after implantation. The hyaluronan content
      of pepsin-solubilized corneal stromal extracts and its distribution (7 microns
      cryostat sections) were investigated using an alkaline phosphatase-linked
      hyaluronectin assay that specifically detects nanogram amounts of hyaluronan. A
      PTFE polymer implant caused large, transient increases in hyaluronan density in
      the implanted stroma. The presence of amphiphilic hyaluronan in the polymer 15
      days post implantation probably produced translucence and wettability of this
      opaque, hydrophobic implant despite the absence of cells. The hyaluronan density
      in the PTFE polymer increased considerably during the first month and then
      decreased to stabilize at a moderate level by the third month. These changes in
      hyaluronan density parallel the invasion of the polymer by inflammatory cells
      during the first month and the subsequent replacement of these cells by
      fibroblasts. The PTFE polymer is a good interface that is compatible with the
      native corneal stroma, and our results indicate that hyaluronan, because of its
      amphiphilic character, plays a major role in the polymer wettability and
      translucence and in the production of typical corneal extracellular matrix within
      the pores of the polymer.

PMID- 9570078
TI  - Kinetics of the homogeneous exchange of alpha-lactalbumin adsorbed on titanium
      oxide surface.
AB  - The homogeneous exchange process whereby alpha-lactalbumine molecules adsorbed on
      hydrophilic titanium oxide particles are replaced by alpha-lactalbumine molecules
      in solution has been investigated by means of a 125I radio-labeling technique,
      alpha-lactalbumine is a compact and highly negatively charged protein, making
      this study complementary to previous work devoted to the general understanding of
      the exchange mechanisms of adsorbed proteins on solid surfaces. The isotherm of
      alpha-lactalbumine exhibits bimodal adsorption shape, and the exchange process
      whereby adsorbed proteins are replaced by new incoming ones from the bulk
      solution has been studied at both the upper and the lower plateau of the
      isotherm. In the upper plateau the exchange process was found to be of first
      order with respect to the bulk molecules, and the release rate constant was equal
      to 0.914 L. mol-1.s-1. This behavior is identical to what has been observed with
      other proteinic systems. In the lower plateau domain, in contrast, the protein
      release process is independent of the concentration of proteins in the bulk, but
      the release rates are higher than the pure desorption rates. This constitutes, to
      our knowledge, a behavior that never before has been observed and that remains to
      be explained.

PMID- 9570079
TI  - Adhesion mechanisms of resin to etched dentin primed with N-methacryloyl glycine
      studied by 13C-NMR.
AB  - The origin of the pH-dependent bond strength of the resin to etched dentin
      treated with N-methacryloyl glycine (NMGly) primer was studied by 13C-nuclear
      magnetic resonance (NMR) including spin-lattice relaxation time, T1, observation.
      When the dentinal collagen was suspended in the NMGly solution at pH = 1.6, the
      T1 values of all the carbons attributed to the NMGly species were significantly
      decreased. This indicated the presence of an interaction between the NMGly and
      the dentinal collagen. To obtain detailed information of this interaction, the
      13C-NMR spectra of the NMGly were measured in the presence of the model compound
      for the collagen, (Pro-Pro-Gly)5 at pH = 1.7. The 13C-NMR peaks of the carbonyl
      carbons of the amide and carboxylic acid in the NMGly species shifted to a higher
      field and the T1 values decreased. Furthermore, when the molar ratio of (Pro-Pro
      Gly)5 to NMGly was decreased from 1:1 to 1:3, the T1 values of the carbonyl
      carbon attributed to the carboxylic acid in the C-terminal Gly residue of the
      oligopeptide decreased dramatically. It can be construed that this indicated the
      formation of a hydrogen bond between the amide, -NH and the carboxylic acid of
      the NMGly species and the carboxylic acid of the C-terminal Gly residue of the
      oligopeptide.

PMID- 9570081
TI  - Comparison of human, primate, and canine femora: implications for biomaterials
      testing in total hip replacement.
AB  - The canine model remains an animal of choice for determining the efficacy and
      safety of various materials and designs used in human total hip replacement
      (THR). The primate also is used in orthopedic-related research for studying limb
      anatomy, gait, and age-related bone loss. In order to better understand the
      appropriateness of these animal models for human THR, external morphologies of
      thirty-three adult Caucasian human, sixteen adult chimpanzee, and forty-two adult
      greyhound femora were compared using osteometric methods. Measured parameters
      included anteversion angle, cervico-diaphyseal angle, femoral head offset in the
      frontal plane, and anterior bow profiles along the femoral diaphysis. Although
      some of the measured parameters were approximately similar between species (e.g.,
      mean cervico-diaphyseal angle of humans and chimpanzees), the majority
      demonstrated morphologic differences that may be biomechanically significant for
      interpreting stress transfer across the hip (e.g., mean anteversion angle and
      mean normalized femoral head offset between species). Additionally, age-related
      changes in proximal femoral morphology and gait pattern, as well as species
      related differences in local muscle and inertial forces, may result in notably
      different loading conditions across the hip joint of each species. Therefore,
      discretion must be exercised when evaluating canine or primate THR materials and
      designs for potential use in the human hip.

PMID- 9570080
TI  - Interfacial phenomena: an in vitro study of the effect of calcium phosphate (Ca
      P) ceramic on bone formation.
AB  - In previous studies we developed a RF magnetron sputter technique for the
      production of thin Ca-P coatings. With this technique coatings can be produced
      that vary in Ca/P ratio as well as in structural appearance. The aim of this
      investigation was to obtain more understanding of the biological behavior of
      these coatings by way of in vitro experiments. The effect of noncoated titanium
      (Ti) and three different Ca-P-sputtered surfaces on the proliferation and
      differentiation (morphology and matrix production) of osteoblast-like cells was
      studied. Proliferation was determined using counting procedures; morphology was
      studied by scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM). Fluorescent markers and energy-dispersive X-ray microanalysis
      (EDX) were used to obtain quantitative and compositional information about the
      resultant calcified extracellular matrix (ECM). Results demonstrated that
      proliferation of the osteoblast-like cells was significantly (p < 0.05) higher on
      noncoated than on Ca-P-coated samples. On the other hand, more mineralized ECM
      was formed on the coated surfaces. In addition, TEM confirmed that the cells on
      the coated substrates were surrounded by ECM with collagen fibers embedded in
      crystallized, needle-shaped structures. On the basis of these findings, we
      concluded that: (1) the investigated Ca-P sputter coatings possess the capacity
      to activate the differentiation and expression of osteogenic cells, and (2) bone
      formation proceeds faster on Ca-P surfaces than on Ti substrates. Further, this
      bone-inductive effect appeared to be dependent on the Ca-P ratio of the deposited
      coatings.

PMID- 9570082
TI  - Composite biomaterials with chemical bonding between hydroxyapatite filler
      particles and PEG/PBT copolymer matrix.
AB  - In an effort to make composites from hydroxyapatite and a PEG/PBT copolymer
      (Polyactive 70/30), chemical linkages were introduced between the filler
      particles and polymer matrix using hexamethylene diisocyanate as a coupling
      agent. Infrared spectra (IR) and thermal gravimetric analysis (TGA) confirmed the
      presence of Polyactive 70/30 on the surface of HA filler particles. The amount of
      chemically bound polymer was 4.7 wt.%, as determined by TGA. The mechanical
      properties of the composites, that is, tensile strength and Young's modulus, were
      improved significantly by the introduction of a chemical linkage between the
      filler particles and polymer matrix compared to control composites. This method
      provides an effective way to introduce chemical linkage between HA filler
      particles and a polymer matrix. By optimizing the grafting process, a further
      improvement of the mechanical properties in the composites can be expected.

PMID- 9570083
TI  - Comparison of tethered star and linear poly(ethylene oxide) for control of
      biomaterials surface properties.
AB  - Four different poly(ethylene oxide) [PEO] molecules were compared as grafted
      polymer layers for biomaterials' substrates: two linear polymers and two star
      polymers. Conditions maximizing surface coverage for each molecule were employed
      with the aim of inhibiting protein adsorption and increasing the density of end
      groups. Neutron reflectivities of the grafted layers immersed in deuterium oxide
      (heavy water) were measured and used to calculate volume fraction profiles of the
      polymer as a function of distance from the surface. These density profiles were
      combined with protein adsorption data on the grafted layers to compare with
      recent theoretical and experimental studies of protein resistance by PEO at
      surfaces. We found that the grafting density is maximized by coupling the linear
      PEO from a K2SO4 salt buffer, which is a poor solvent for PEO. However, the
      grafting density of star PEO was maximized when no K2SO4 was used and the stars
      were dissolved near the overlap concentration. Concentration profiles obtained
      from the reflectivity data show that the hydrated polymers swell to approximately
      10 times the dried layer thickness and exhibit a low density (maximum volume
      fractions < 0.4 PEO) throughout the layer. The PEO surfaces obtained with both
      the star and linear polymers resisted adsorption of cytochrome-c and albumin
      except for a small amount of cytochrome-c adsorption on the short, many-armed
      star polymer surface. A hypothesis of adsorption on the star polymer layer is
      presented and criteria for controlling receptor-mediated cell-substrate
      interactions by ligand-modified chain ends are discussed.

PMID- 9570084
TI  - Protein secondary structure templates derived from bioactive natural products.
      Combinatorial chemistry meets structure-based design.
AB  - Lead finding strategies in pharmaceutical research comprise structure-based drug
      design as well as screening efforts of natural product pools or large chemical
      libraries. In this context we propose a combined approach by utilizing natural
      product-derived structure information on receptor- or enzyme-complementary for
      designing unique core structures that can be employed as privileged template
      molecules underlying combinatorial libraries. A set of rules for the
      transformation of molecular frameworks from natural products to structurally
      defined peptidomimetics is introduced. Special emphasis is laid on the
      correspondence in the orientational properties and functionalization patterns
      between natural products and regular protein secondary structures.

PMID- 9570085
TI  - A proposed bioactive conformation of peptide T.
AB  - The conformational profiles of Peptide T, (5-8)Peptide T, [Abu5](4-8)Peptide T
      and (4-8)Peptide T were computed independently to assess the geometrical
      characteristics of the bioactive conformation of Peptide T. The conformational
      profiles of the peptides were computed within the molecular mechanics framework
      using an effective dielectric constant of 80. The conformational space was
      thoroughly sampled using an iterative simulated annealing protocol. The bioactive
      conformation was assessed by pairwise cross comparisons of each of the unique low
      energy conformations found for each of the different analogs studied. After a
      putative bioactive conformation was selected, in order to further validate our
      hypothesis the conformational profile of the potent compound cyclo(Thr-Thr-Asn
      Tyr-Thr-Asp) was computed and the putative bioactive conformation was found. The
      conformation exhibits a pseudo beta-turn involving the side chain of Thr5 and the
      carbonyl oxygen of Tyr7 forming a C12 ring.

PMID- 9570086
TI  - Prediction of the binding mode of N2-phenylguanine derivative inhibitors to
      herpes simplex virus type 1 thymidine kinase.
AB  - The probable binding mode of the herpes simplex virus thymidine kinase (HSV1 TK)
      N2-[substituted]-phenylguanine inhibitors is proposed. A computational experiment
      was designed to check some qualitative binding parameters and to calculate the
      interaction binding energies of alternative binding modes of N2-phenylguanines.
      The known binding modes of the HSV1 TK natural substrate deoxythymidine and one
      of its competitive inhibitors ganciclovir were used as templates. Both the
      qualitative and quantitative parts of the computational experiment indicated that
      the N2-phenylguanine derivatives bind to the HSV1 TK active site in the
      deoxythymidine-like binding mode. An experimental observation that N2
      phenylguanosine derivatives are not phosphorylated during the interaction with
      the HSV1 TK gives support to the proposed binding mode.

PMID- 9570087
TI  - Ligand binding affinity prediction by linear interaction energy methods.
AB  - A recent method for estimating ligand binding affinities is extended. This method
      employs averages of interaction potential energy terms from molecular dynamics
      simulations or other thermal conformational sampling techniques. Incorporation of
      systematic deviations from electrostatic linear response, derived from free
      energy perturbation studies, into the absolute binding free energy expression
      significantly enhances the accuracy of the approach. This type of method may be
      useful for computational prediction of ligand binding strengths, e.g., in drug
      design applications.

PMID- 9570088
TI  - Charge distribution from a simple molecular orbital type calculation and non
      bonding interaction terms in the force field MAB.
AB  - A simple and fast method to calculate charge distributions in organic molecules
      is presented. The method is based on charge shifts within the saturated sigma
      system, driven by orbital electronegativities, coupled to a modified Huckel
      treatment of the unsaturated pi-systems. Experimental molecular dipole moments of
      a set of 119 molecules are reproduced with a root mean square deviation of 0.36
      Debye units. Furthermore, the obtained charge distribution is used to describe
      hydration free energies in terms of hydrogen-bonding donor and acceptor strengths
      of polar groups. Least square fitting to experimental data of 281 compounds leads
      to values for these strengths with accuracy limits of +/- 4.3% and +/- 2.5%,
      respectively. Properly normalized values are taken to parametrize the hydrogen
      bonding terms in our MAB force field. The method is sufficiently fast to be used
      in the preparatory phase of interactive force-field calculations.

PMID- 9570089
TI  - Predicting nucleic acid torsion angle values using artificial neural networks.
AB  - By means of an error back-propagation artificial neural network, a new method to
      predict the torsion angles, chi, zeta and alpha from torsion angles delta,
      epsilon, beta and gamma for nucleic acid dinucleotides is introduced. To build a
      model, training sets and test sets of 163 and 81 dinucleotides, respectively,
      with known crystal structures, were assembled. With 7 hidden units in a three
      layered network a model with good predictive ability is constructed. About 70 to
      80% of the residuals for predicted torsion angles are smaller than 10 degrees.
      This means that such a model can be used to construct trial structures for
      conformational analysis that can be refined further. Moreover, when reasonable
      estimates for delta, epsilon, beta and gamma are extracted from COSY experiments,
      this procedure can easily be extended to predict torsion angles for structures in
      solution.

PMID- 9570090
TI  - Classification of auxin plant hormones by interaction property similarity
      indices.
AB  - Although auxins were the first type of plant hormone to be identified, little is
      known about the molecular mechanism of this important class of plant hormones. We
      present a classification of a set of about 50 compounds with measured auxin
      activities, according to their interaction properties. Four classes of compounds
      were defined: strongly active, weakly active with weak antiauxin behaviour,
      inactive and inhibitory. All compounds were modeled in two low-energy
      conformations, 'P' and 'T', so as to obtain the best match to the 'planar' and
      'tilted' conformations, respectively, of indole 3-acetic acid. Each set of
      conformers was superimposed separately using several different alignment schemes.
      Molecular interaction energy fields were computed for each molecule with five
      different chemical probes and then compared by computing similarity indices.
      Similarity analysis showed that the classes are on average distinguishable, with
      better differentiation achieved for the T conformers than the P conformers. This
      indicates that the T conformation might be the active one. Further, a screening
      was developed which could distinguish compounds with auxin activity from inactive
      compounds and most antiauxins using the T conformers. The classifications
      rationalize ambiguities in activity data found in the literature and should be of
      value in predicting the activities of new plant growth substances and herbicides.

PMID- 9570091
TI  - A multiway 3D QSAR analysis of a series of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]
      6-methoxybenzamides.
AB  - Recently, the multilinear PLS algorithm was presented by Bro and later
      implemented as a regression method in 3D QSAR by Nilsson et al. In the present
      article a well-known set of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6
      methoxybenzamides, with affinity towards the dopamine D2 receptor subtype, was
      utilised for the validation of the multilinear PLS method. After exhaustive
      conformational analyses on the ligands, the active analogue approach was employed
      to align them in their presumed pharmacologically active conformations, using (-)
      piquindone as a template. Descriptors were then generated in the GRID program,
      and 40 calibration compounds and 18 test compounds were selected by means of a
      principal component analysis in the descriptor space. The final model was
      validated with different types of cross-validation experiments, e.g. leave-one
      out, leave-three-out and leave-five-out. The cross-validated Q2 was 62% for all
      experiments, confirming the stability of the model. The prediction of the test
      set with a predicted Q2 of 62% also established the predictive ability. Finally,
      the conformations and the alignment of the ligands in combination with
      multilinear PLS, obviously, played an important role for the success of our
      model.

PMID- 9570092
TI  - Determination of arsenic in hair using neutron activation.
AB  - Arsenic concentrations were measured in scalp hair of three groups of people of a
      village in west of Iran. One group consisted of healthy subjects, the second of
      subjects with suspected arsenic poisoning and the third with people infected with
      arsenic poisoning. The measurements were carried out using neutron activation
      analysis at Tehran Research Reactor. Along with these measurements, the arsenic
      content of water sources used by the inhabitants were also measured. The
      measurements revealed that the average arsenic concentration in the healthy group
      was 0.2 +/- 0.07 ppm, in the suspected group was 4.9 +/- 0.5 ppm, in the infected
      group was 5.6 +/- 0.5 ppm and in water samples varied between 0.03 +/- 0.01 and
      1.04 +/- 0.10 ppm.

PMID- 9570093
TI  - Use of charged particle activation as an analytical technique in the biological
      field.
AB  - Some applications of Charged Particle Activation Analysis (CPAA) in the
      biological field are presented. This technique has been used frequently for the
      analysis of the light elements which are inaccessible to neutron activation
      analysis (NAA), but it is especially effective in the detection of medium-heavy
      trace elements and there is increasing interest in its employment in biological
      and medical fields. CPAA enables the identification and simultaneous
      quantification of different isotopes of the same element. Recent applications
      show that it can be used as a reference method in stable isotope determination
      for biokinetic studies of selected elements in complex organic matrices such as
      blood plasma.

PMID- 9570094
TI  - Changes in contents and in vitro digestibility of laying-hens excreta used as
      feedstuffs due to drying and gamma irradiation.
AB  - Experiments have been carried out to study the changes in the values of total
      nitrogen (N), in vitro digestible crude protein (IVDCP), in vitro apparent
      organic matter digestibility (IVOMD), in vitro digestible energy (IVDE), crude
      fibre (CF) and cell-wall constituents (NDF, ADF, ADL) for laying-hens excreta
      under the effects of: (1) two types of drying: (a) drying at 175 degrees C for 10
      minutes (D1); (b) drying at 55 degrees C for 5 days (D2). (2) different doses of
      gamma irradiation [0, 10, 50, 100, 150 kilogray (kGy)]. The results indicated
      that there was a significant (P < 0.05) decrease in values of NDF and ADF (by
      7%), CF and IVDCP (by 13%), and N (by 16%), and a significant increase in the
      values of IVOMD (by 12%) and IVDE (by 630 kJ/kg DM) as a result of drying (D1) in
      comparison with drying (D2). A significant (P < 0.05) decrease was observed in
      the values of NDF and ADF (by 6%), CF (by 12%) and a significant increase in the
      values of IVOMD (by 13%) and IVDE (by 980 kJ/kg DM) as a result of gamma
      irradiation treatment (100 kGy) in comparison to the control sample. There was no
      significant difference between doses (100 kGy and 150 kGy). Gamma irradiation had
      no effect on N, ADL and IVDCP values. Combined treatment (D1 + 100 kGy) resulted
      in a better effect in reducing the concentrations of CF, NDF and ADF and in
      increasing the values of IVOMD and IVDE.

PMID- 9570095
TI  - Mineral content of medicinal plants used in the treatment of diseases resulting
      from urinary tract disorders.
AB  - Elemental composition of some Ayurvedic medicinal plants used for healing urinary
      tract disorders has been studied by nondestructive neutron activation analysis
      with a 252Cf source and atomic absorption spectroscopy. In total, 14 elements
      have been estimated in different plants; among these Cu, Cr, Co and Cd are found
      to be present at the trace level; Mn, Pb, Zn, Ni, Na, Fe and Hg at minor level
      and K, Ca and Cl at major level. The differences in the concentration of the
      elements are attributed to soil composition and the climate in which the plant
      grows. The importance of some elements in diseases related to renal disorders is
      also briefly discussed.

PMID- 9570096
TI  - A process for the recovery of strontium from the urine of patients injected with
      89Sr.
AB  - 89Sr is a beta emitter used for palliation of pain in patients with metastatic
      bone cancer. After each intravenous administration, up to 80% of the isotope is
      eliminated in the urine. A simple chemical process is described, which permits
      the recovery and purification of the 89Sr from the urine.

PMID- 9570098
TI  - Use of Chinese LiF:Mg,Cu,P (GR-200) TL detectors at therapy-level absorbed doses.
AB  - The objective was to find out whether or not the highly radiation-sensitive
      Chinese thermoluminescent (TL) LiF:Mg,Cu,P (GR-200) detector pellets can be used
      in therapy-level dosimetry. For this purpose the precision was investigated at an
      absorbed dose level of 1 Gy using a commercial TL read-out instrument. Relative
      standard deviations, sigma rel, of the individual calibration factors were found
      to be in the range between 0.2% and 0.6% from 30 randomly selected detectors,
      with the mean at 0.37%. Apart, linearity checks between 1 and 6 Gy resulted into
      a sublinear response of up to -4% which was successfully corrected for by a third
      order polynomial curve fit. The residual signal turned out to be about 0.1% after
      one annealing cycle almost independent of the applied dose, and this figure could
      be reduced by two more decades after repeated annealing cycles.

PMID- 9570097
TI  - Radiation dose to the human respiratory tract from inhalation of radon-222 and
      its progeny.
AB  - In this article the regional dose equivalent for exposure to 1 working level
      month (WLM), the annual effective dose equivalent and the dose equivalent
      conversion factor due to the inhalation of short-lived radon progeny (218Po,
      214Pb and 214Bi/214Po) are calculated with a dosimetric model. Experimental
      results of aerosol size characteristics, unattached activity fractions,
      equilibrium factors, and activity size distributions of the short-lived radon
      progeny in indoor and outdoor atmosphere are summarized. Dose calculations based
      on these results show that the changes in dose rate values are influenced by the
      different model assumptions concerning deposition probabilities of aerosol
      particles in the respiratory system during inhalation, the sensitivity of
      different cells (epithelial, basal) to radiation and assuming nose or mouth
      breathing. The inverse relationship between the unattached fraction of potential
      alpha-particle energy in room air and the radioactive equilibrium between radon
      gas and its progeny indicates that dose equivalent is closely related to the
      concentration of radon gas averaged over a period of exposure.

PMID- 9570099
TI  - Labeling of penicillamine di sulfide with technetium-99m.
AB  - Complex forming conditions of Penicillamine di sulfide with 99mTc have been
      specified. Labeling of penicillamine di sulfide with 99mTc by direct reduction
      with SnCl2 did not give favorable good results while the 99mTc complex of
      penicillamine can be easily obtained. Ligand exchange reaction with 99mTc
      gluconate was attempted and a 95% labeling efficiency was obtained.
      Radiopharmaceutical potential of 99mTc-PADS (99mTc-Penicillamine di sulfide) has
      been investigated with a gamma camera in rabbits and the complex was found to be
      uptaken mostly by the liver and kidneys.

PMID- 9570100
TI  - Enzymatic synthesis of [4-methoxy-11C]daunorubicin for functional imaging of P
      glycoprotein with PET.
AB  - One of the mechanisms for multidrug resistance (MDR) of tumors is an
      overexpression of the P-glycoprotein (P-gp). The cytostatic agent daunorubicin
      was labeled with carbon-11 to probe P-gp with PET. An enzymatic route for the
      conversion of carminomycin to [4-methoxy-11C]daunorubicin ([4-methoxy-11C]DNR)
      was investigated, since attempts failed to prepare daunorubicin chemically using
      [11C]methyl iodide. In the enzymatic synthesis methylation was accomplished by S
      adenosyl-L-[methyl-11C]methionine ([11C]SAM), which was synthesized from L
      [methyl-11C]methionine. This methylation is catalyzed by carminomycin-4-O
      methyltransferase (CMT). The overall radiochemical yield of [4-methoxy-11C]DNR is
      1% (EOB), with a total synthesis time of 75 min. In conclusion, [4-methoxy
      11C]DNR can be successfully prepared from carminomycin and [11C]SAM using
      enzymes.

PMID- 9570102
TI  - Level of natural and artificial radioactivity in Algeria.
AB  - A national environmental sampling program was carried out during 1993 to
      determine natural and artificial radionuclides contents in the (0-15 cm) upper
      layer of the soil. The main objective was to establish a radioactive reference
      level in the whole territory, since 131I, 134Cs and 137Cs were detected in most
      of the analysed samples collected right after the Chernobyl accident (May 1986).
      Soil samples were analysed by direct counting by gamma-ray spectrometry. In
      addition, terrestrial gamma-ray dose rates in air have been measured out of doors
      throughout Algeria. In each of the 48 administrative divisions of the country
      selected sites were chosen to collect soil samples and measure gamma-ray dose
      rates. The gamma-emitting radionuclides resulting from the radioactive decay of
      238U and 232Th, 40K and 137Cs were detected in most of the analysed samples.
      Radioactivity concentrations in Bq kg-1 dry mass in soil samples of 226Ra, 214Pb,
      214Bi, 212Pb, 228Ac, 40K and 137Cs range between (5-176), (2-107), (3-65), (2
      97), (3-144), (36-1405) and (0.3-41) respectively. In addition, six selected soil
      samples were analysed to determine plutonium isotopes contents. Radioactivity
      concentrations in Bq kg-1 dry mass of 238Pu and 239 + 240Pu vary between (0.012
      0.013) and (0.24-0.61) respectively. The dose rates in air measured over the
      whole country were found to range between 20 and 133 nGy h-1. Presence of 137Cs
      has been clearly observed. An approach has been made to determine its origin,
      considering the global fallout, the Chernobyl accident and the French nuclear
      bomb tests in the 60s as the main potential sources. It is concluded that Algeria
      has indeed been affected by the Chernobyl accident.

PMID- 9570101
TI  - Assay of 222Rn in water samples by a modified integral counting method.
AB  - 22Rn activity concentrations in water collected from 163 private wells and 14
      springs in Tokyo were measured with a liquid scintillation spectrometer using a
      modified integral counting method. The activity concentrations of 222Rn range
      from 0.2 to 22.9 Bq/L and average 4.8 Bq/L. The errors due to the air
      luminescence counts and the interferences from 220Rn and 219Rn are discussed and
      evaluated. 222Rn samples of 0.2 Bq/L can be assayed within an overall uncertainty
      of 3.1%. The liquid scintillation method involving agitation of the sample water
      directly with a liquid scintillation cocktail was compared with the present
      method and evaluated.

PMID- 9570104
TI  - Gross alpha- and beta-activities in surface and ground water of Rio Grande do
      Norte, Brazil.
AB  - Gross alpha- and beta-activities were determined on 37 fresh water samples
      collected from 14 artificial basins, 13 deep drilled wells, two dug wells, two
      lakes, two rivers, one spring, and a tap belonging to 30 locations scattered
      throughout the eastern and central parts of the Brazilian state of Rio Grande do
      Norte. The surveyed area was about 35,000 km2 with a lithology including both
      crystalline (18 towns) and sedimentary (12 towns) rocks. Concentrations ranging
      from < 2.8 to 354 Bq m-3 and from 50.5 to 580 Bq m-3 were observed for the gross
      alpha- and beta-activities, respectively. For the gross beta-activity, which was
      always higher than the corresponding alpha-activity, the arithmetic mean with its
      standard deviation was 226 +/- 154 Bq m-3. In order to evaluate the radioactive
      dose due to the ingestion of these waters, a conservative dosimetric calculation
      was carried out using the dose conversion factors suggested by the ICRP. An
      average annual effective dose equivalent of 60 +/- 42 microSv was obtained
      together with a range of 14-161 microSv y-1.

PMID- 9570103
TI  - Extractive procedure for uranium determination in water samples by liquid
      scintillation counting.
AB  - An extractive procedure for uranium determination using liquid scintillation
      counting with the URAEX cocktail is described. Interference from radon and a
      strong influence of nitrate ion were detected in this procedure. Interference
      from radium, thorium and polonium emissions were very low when optimal operating
      conditions were reached. Quenching effects were considered and the minimum
      detectable activity was evaluated for different sample volumes. Isotopic analysis
      of samples can be performed using the proposed method. Comparisons with the
      results obtained with the general procedure used in alpha spectrometry with
      passivated implanted planar silicon detectors showed good agreement. The proposed
      procedure is thus suitable for uranium determination in water samples and can be
      considered as an alternative to the laborious conventional chemical preparations
      needed for alpha spectrometry methods using semiconductor detectors.

PMID- 9570105
TI  - AOX-emissions from hospitals into municipal waste water.
AB  - Adsorbable organically bound halogens (AOX) are mostly persistent in the
      environment, and accumulate in the food web. Some of them are toxic to humans and
      other organisms. AOX were measured in the effluents from six German hospitals of
      different size and departments like internal medicine and ear-nose and throat
      (ENT) as well as from laundry, kitchen and laboratory. The concentrations in the
      day time mixed samples of the total effluent were 0.13 mg l(-1)-0.94 mg l-1 (phi
      = 0.43 mg l-1). For the separately investigated departments the lowest
      concentrations were found in the effluent from laundry and kitchen (0.015 mg l
      1), and the highest ones in the effluents from the medical departments (0.12-1.71
      mg l-1, phi 0.95 mg l-1 during the week and 0.06-0.10 mg l-1 at the week-end) and
      the laboratories (0.05-14.2 mg l-1, phi 2.73 mg l-1). The AOX concentration in
      night time mixed samples were 0.07-0.41 mg l-1 (phi = 0.41 mg l-1) for the total
      effluents and 0.25-2.64 mg l-1 (phi = 1.11 mg l-1) for medical departments.
      Concentrations expected by computing the input of AOX attributable to
      pharmaceuticals were between 11% and 16% for two hospitals and 7.7% for an ENT
      department. One additional important source of AOX in hospital effluents may be x
      ray contrast media containing a iodine carbon bond.

PMID- 9570106
TI  - Development and validation of methods for the trace determination of PCBs in
      biological matrices.
AB  - A method was developed to determine trace concentrations of a range of individual
      PCB congeners in biological samples (grass, silage, cattle faeces and milk-fat)
      which were taken from rural or 'background' areas of the UK, in order to prepare
      a mass balance of PCBs in grazing, lactating cows. A simple milk-fat extraction
      method was compared to Soxhlet extraction and to whole milk extraction. Results
      indicated that simply boiling milk-fat in hexane with sodium sulphate present
      gave a comparable extraction of PCBs to other methods. A clean-up method was
      devised using acid treated silica gel followed by basic alumina chromatography.
      Grinding frozen grass or silage with sodium sulphate followed by Soxhlet
      extraction was found to be the most effective method for these matrices, whilst
      avoiding the potential contamination/loss of PCBs which can be incurred by air,
      oven or freeze drying. Soxhlet extraction of cattle faeces, after grinding with
      sodium sulphate, was found to be effective. A rigorous clean-up was devised which
      involved passing the extracts through silica gel and acid treated silica gel,
      followed by size exclusion chromatography (gel permeation chromatography, SEC).
      13C12 labelled PCBs were used as recovery standards, quantification was performed
      using GC-MS. A quality control regime and method validation results are
      presented. The milk analysis method gave within batch mean recoveries of 69-96%,
      and within batch standard deviations between 1 and 10%. The vegetation analysis
      method gave within batch mean recoveries of 91-116%, and within batch standard
      deviations between 1 and 11%. The batch to batch mean recovery for milk analysis
      was 90%, with an RSD of 2% for high spikes and 5% for low spikes; for vegetation
      analysis the batch to batch average recovery was 106%, with an RSD of 14% for
      high spikes and 11% for low spikes. sigma PCB concentrations (53 congeners) of
      3900 +/- 790 pg g-1 milk-fat, 1300 +/- 420 pg g-1 dry matter (DM) cattle faeces,
      630 +/- 140 pg g-1 DM silage and 1350 +/- 580 pg g-1 DM grass were found during
      the study.

PMID- 9570107
TI  - Dioxin levels in the emissions from municipal waste incinerators in Taiwan.
AB  - In this study, characteristics of dioxins emission from existing modern MWIs were
      evaluated via simultaneous sampling of flue gas and various types of fly ashes.
      Preliminary results showed that PCDDs congeners distributions were quite similar
      in flue gas and various types of ashes of both MWIs. PCDFs/PCDDs ratio in cyclone
      ash was lower than that in combustor ash or fabric filter ash excluding
      economizer ash of MWI-A. Similarly, PCDFs/PCDDs ratio in ESP ash was lower than
      that in boiler ash. PCDFs concentration was about 1.5 to 4.3 times higher than
      PCDDs concentration in flue gas of both MWIs. The mass balance factors of MWI-A
      (0.9 approximately 1.02) were clearly lower than that of MWI-B (7.71
      approximately 15.63), indicating that de novo synthesis occurred under the
      operating conditions of ESP. In other words, MWIs equipped with ESP were less
      efficient in controlling PCDD/Fs emissions than that equipped with fabric
      filters.

PMID- 9570108
TI  - High performance liquid chromatographic determination of mercapturic acids in
      urine of rats administered with m- or p-xylene.
AB  - The determination of urinary mercapturic acid, N-acetyl-S-(m-xylyl)-L-cysteine or
      N-acetyl-S-(p-xylyl)-L-cysteine, was undertaken by HPLC after i.p. administration
      of m- or p-xylene to rats in order to confirm the structure of thioether which
      was known to be excreted in small amounts related with the metabolism of m- or p
      xylene. The excretion rates of these mercapturic acids were much lower than those
      previously estimated from thioether determinations. The present study clearly
      demonstrates the mercapturic acid pathway operates only to limited degree as a
      metabolic route of m- or p-xylene.

PMID- 9570109
TI  - Developments in solar photocatalysis for water purification.
AB  - Photocatalytic processes in the presence of titanium dioxide provide an
      interesting route to destroy hazardous organic contaminants, being operational in
      the UV-A domain with a potential use of solar radiation. In this paper, some
      specific contaminant classes of interest such as ethylbenzene, gamma-lindane and
      EPTC have been tested at laboratory scale and in the field to determine the
      feasibility of the photocatalytic oxidation of organic contaminants in water. Our
      preliminary results at laboratory scale with these chemicals have provided a
      better understanding of the photocatalytic process which seems to be efficient
      and not selective. The application of these processes in removal of gamma-lindane
      from water operating in a parabolic trough concentrator has demonstrated to be
      effective, being possible to reduce 99.9% of gamma-lindane levels in water in
      acceptable times.

PMID- 9570110
TI  - Elimination kinetics and toxicity of 2,3,7,8-tetrachlorothianthren, a thio
      analogue of 2,3,7,8-TCDD.
AB  - In comparison to the polychlorinated dibenzo-p-dioxins (PCDD) informations on
      their thio analogues the polychlorinated thianthrens (PCTA) are very limited. In
      this study we investigated the kinetics and toxicity of 2,3,7,8
      tetrachlorothianthren (TCTA), the analogue of the most toxic PCDD congener
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It was found that TCTA is rapidly
      eliminated in mouse liver homogenate fortified with an NADPH-regenerating system
      suggesting rapid metabolic degradation by liver monooxygenases. Furthermore, TCTA
      was rapidly eliminated from mouse liver and whole body. In accordance with this
      rapid elimination, a weekly dosage of 1mg TCTA per kg body weight (i.p.) over six
      weeks did not result in weight loss or other signs of overt toxicity in male
      mice. In rat hepatocytes in primary culture, TCTA was active as inducer of dioxin
      receptor-regulated cytochrome P4501A1 activity measured as 7-ethoxyresorufin O
      deethylase (EROD). The relative inducing potency was about 0.0001 in comparison
      to TCDD. In spite of this molecular effects, the rapid elimination both in vitro
      and in vivo argues against a consideration of a TCDD equivalency factor for TCTA.

PMID- 9570111
TI  - Mixture toxicity and tissue interactions of Cd, Cu, Pb and Zn in earthworms
      (Oligochaeta) in laboratory and field soils: a critical evaluation of data.
AB  - Soil organisms inhabiting contaminated field sites are usually exposed to
      mixtures of toxicants. In such mixtures, toxicants can interact to express
      enhanced or weakened toxicity. Therefore, mixture effects should be considered in
      risk assessment methods for polluted soils. Data on mixture toxicity to soil
      organisms are scarce, however. In this paper, data on sublethal toxicity and
      tissue concentrations of Cd. Cu, Pb and Zn mixtures in earthworms are evaluated
      and compared with data on other organisms. Toxic effects were mainly antagonistic
      for total soil concentrations and nearly concentration-additive for 0.01 M CaCl2
      extractable soil concentrations. Evidence to support concentration-additive
      behaviour of metals was found in interaction patterns within earthworm tissues. A
      method is proposed to assess the sublethal toxicity of metal mixtures in field
      soils to earthworms, based on single metal experiments from the laboratory.
      Finally, suggestions are made on how to incorporate mixture toxicity in risk
      assessment for polluted soils.

PMID- 9570112
TI  - Computer modelling of dynamics of Ser92X deoxymyoglobin mutants.
AB  - The hydrogen bond between His93 and Ser92, recently discovered in crystal
      structures of myoglobins (Mbs), may contribute to the oxygen storage capacity of
      the heme proteins through a stabilization of the proximal ligand. The possible
      influence of this H-bond on the geometry of the heme proximal side and ligand
      binding properties of Mb were computationally studied using model proteins with
      point mutations affecting this bond. The results of the computer modelling of
      Ser92X (X = Ala, Ile, Thr, Val) mutants of human (H) and sperm whale (SW) Mbs are
      presented. The OPLS-AMBER-CHARMM forcefield was used in the calculations. Several
      10-50 ps molecular dynamics simulations (300 K, in vacuo) were performed. Our
      results show that the Ser92X mutants are stable molecules. In the wild types and
      Ser92Thr mutants, the H-bond studied is observed only for a relatively short
      period of time. It is expected that in both HMb and SW Mb molecules the impact of
      the proximal histidine interaction with the Ser92(F7) residue on the iron
      reactivity is rather low. However, the limited torsional flexibility of the
      proximal histidine imidazole ring was found in hydrogen bonding mutants. This
      effect may be attributed to the specific long range electrostatic interactions.

PMID- 9570113
TI  - A new algorithm for analysis of the homology in protein primary structure.
AB  - A new algorithm for analysis of the homology and genetic semihomology in protein
      sequence is described. It assumes the close relation between the compared amino
      acids and their codons in related proteins. The algorithm is based on the network
      of the genetic relationship between amino acids and, thus differs from the
      commonly used statistical matrices. The results obtained by using this method are
      more comprehensive than used at present, and reflect the actual mechanism of
      protein differentiation and evolution. They concern: (1) location of homologous
      and semihomologous sites in compared proteins; (2) precise estimation of
      insertion/deletion gaps in non-homologous fragments; (3) analysis of internal
      homology and semihomology; (4) precise location of domains in multidomain
      proteins; (5) estimation of genetic code of non-homologous fragments; (6)
      construction of genetic probes; (7) studies on differentiation processes among
      related proteins; (8) estimation of the degree of relationship among related
      proteins; (9) studies on the evolution mechanism within homologous protein
      families and (10) confirmation of actual relationship of sequences showing low
      degree of homology.

PMID- 9570114
TI  - Molecular cloning, expression, and characterization of dnaK in Streptococcus
      pneumoniae.
AB  - DnaK is known to be highly conserved in all species and is a major immunogen in
      Streptococcus pneumoniae. To elucidate the role of dnaK in S. pneumoniae, dnaK
      was cloned in Escherichia coli using a homologous dnaK probe generated by PCR.
      The His-tagged DnaK was overexpressed in soluble form and purified from E. coli.
      Alignment of the deduced DnaK amino acid sequence from nucleotide sequences of
      the cloned dnaK revealed high homology with DnaK analogs in E. coli (53%) and
      Staphylococcus aureus (73%). However, anti-pneumococcal DnaK antiserum did not
      crossreact with DnaK analogs in E. coli, S. aureus and human cells suggesting
      that pneumococcal DnaK might be a good candidate as a vaccine.

PMID- 9570115
TI  - Panmictic structure of Helicobacter pylori demonstrated by the comparative study
      of six genetic markers.
AB  - We compared the classifications of strains obtained by analysis of several
      genetic markers to demonstrate the panmictic structure of Helicobacter pylori,
      previously suggested by the study of multilocus enzyme electrophoresis. A series
      of 39 strains, including 37 clinical isolates from patients with gastritis or
      ulcers from two regions of France, reference strain CIP 101260 and the Sydney
      strain (strain SSI), were used. They were studied by restriction fragment length
      polymorphism analysis of ribosomal DNA (ribotyping) using HindIII and HaeIII, by
      polymorphism analysis of the ureA-ureB and flaA genes by PCR-RFLP using HaeIII
      and MboI, by vacA genotyping and by the presence or absence of the cagA gene and
      of the insertion sequence IS605 detected by PCR. There was a high level of
      genetic polymorphism over the studied strains, with 38 ribotypes, 38 restriction
      profiles for the ureA-ureB gene, 19 restriction profiles for the flaA gene and
      five combinations of the signal and mid-region sequences of the vacA gene.
      Factorial analysis of correspondence and hierarchical clustering performed using
      each marker revealed that the different classifications of the strains were not
      correlated. This suggests there is much genetic recombination between strains and
      supports the hypothesis of a panmictic structure for the H. pylori species.

PMID- 9570116
TI  - Decreased membrane permeability in a polymyxin B-resistant Escherichia coli
      mutant exhibiting multiple resistance to beta-lactams as well as aminoglycosides.
AB  - A laboratory mutant of Escherichia coli stably resistant to more than 36,000 U ml
      1 of polymyxin B was isolated. The mutant exhibited moderate increases in minimum
      inhibitory concentration to fluoroquinolones and bacitracin but high levels of
      cross-resistance to beta-lactams and aminoglycosides. However, it remained
      susceptible to tetracycline, nalidixic acid and novobiocin. Changes were observed
      in the outer membrane proteins and lipopolysaccharide profile leading to a
      decrease in permeability as evident from reduction in the following: (i) minimum
      inhibitory concentration values in the presence of Tween 80, (ii) uptake of 1-N
      phenyl naphthylamine and norfloxacin, (iii) hydrolysis of beta-lactams and (iv)
      diffusion of lactose and cefazolin into proteoliposomes reconstituted with outer
      membrane proteins. We therefore suggest that the novel pattern of cross
      resistance of our isolate is due to the decrease in its permeability.

PMID- 9570117
TI  - Bacterial isolates degrading aliphatic polycarbonates.
AB  - Bacteria that degrade an aliphatic polycarbonate, poly(hexamethylene carbonate),
      were isolated from river water in Ibaraki. Prefecture, Japan, after enrichment in
      liquid medium containing poly(hexamethylene carbonate) suspensions as carbon
      source, and dilution to single cells. Four of the strains, 35L, WFF52, 61A and
      61B2, degraded poly(hexamethylene carbonate) on agar plate containing suspended
      poly(hexamethylene carbonate). Degradation of poly(hexamethylene carbonate) was
      confirmed by gel permeation chromatography. Besides poly(hexamethylene
      carbonate), the strains were found to degrade poly(tetramethylene carbonate). The
      strains were characterized morphologically, physiologically, and by 16S rDNA
      sequence analysis. Strains 35L and WFF52 were tentatively identified as
      Pseudomonas sp. and Variovorax sp., respectively, while strains 61A and 61B2
      constitute an unidentified branch within the beta subclass of the Proteobacteria.

PMID- 9570118
TI  - Green fluorescent protein as a novel marker and reporter system in Helicobacter
      sp.
AB  - In order to be able to study gene regulation in single, live Helicobacter pylori
      bacteria in vitro or in contact with host cells, we established the green
      fluorescent protein gene gfp from Aequorea victoria as a reporter gene for use
      with Helicobacter species. We describe here the construction of genomic
      transcriptional fusions of the promoterless gfp gene with the flaA and flaB
      promoters of H. pylori. We have also constructed a Mini-Tn3-km-gfp transposon to
      be used for shuttle transposon mutagenesis in H. pylori and H. mustelae. A marker
      strain with wild-type phenotype, carrying multiple plasmid-borne copies of gfp
      under the control of the H. pylori flaB promoter, was constructed for studies of
      bacterial distribution and transmission in animal models.

PMID- 9570119
TI  - Decreased symbiotic effectiveness of Rhizobium leguminosarum strains carrying
      plasmid RP4.
AB  - The presence of derivatives of the broad host range plasmid RP4 in strains of
      Rhizobium leguminosarum biovar viciae severely inhibited nitrogen fixation by
      these strains in nodules on cultivars of pea (Pisum sativum). The strains formed
      small white nodules. Yield and total nitrogen values were comparable with those
      obtained for plants inoculated with a non-nodulating mutant. Strains carrying the
      same derivatives gave rise to nitrogen fixing nodules when inoculated on
      cultivars of lentils (Lens culinaris). Similar results were observed with plasmid
      R702 but not with R751, suggesting that the effect is limited to plasmids of the
      IncP alpha classification. Histological examination of nodules induced by strains
      carrying RP4 indicated that there are fewer infected cells and starch granules
      are organised unusually in the infected cells. Tn5 mutagenesis of plasmid RP4-4
      was undertaken and Tn5 inserts were screened for abolition of the effect on
      nitrogen fixation. Eight mutants, having no effect on nitrogen fixation, were
      isolated. Seven of these had lost the ability to transfer by conjugation and the
      eighth was greatly reduced in conjugation frequency. Physical analysis of the
      transposon inserts revealed that they were located in the Tra regions of RP4.

PMID- 9570120
TI  - Obligate phototrophy in cyanobacteria: more than a lack of sugar transport.
AB  - DNA hybridization using the Synechocystis PCC6803 glucose transporter gene, glcP,
      revealed a single homologous region in two facultative photoautotrophic strains
      out of three tested, and none in three obligate autotrophs. In one of the latter,
      Synechococcus PCC7942, integration of glcP into the chromosome resulted in
      glucose sensitivity. A subclone isolated as glucose-tolerant had lost glcP.
      Integration in a replicative vector allowed glucose transport and
      photoheterotrophic growth, but could not be maintained. Thus lack of sugar
      transport could explain cyanobacterial obligate autotrophy. However, at least in
      Synechococcus PCC7942, acquisition of such a transport capacity created a
      metabolic disequilibrium barely compatible with survival.

PMID- 9570121
TI  - Construction and characterization of an NaCl-sensitive mutant of Halomonas
      elongata impaired in ectoine biosynthesis.
AB  - Using transposon mutagenesis we generated a salt-sensitive mutant of the
      halophilic eubacterium Halomonas elongata impaired in the biosynthesis of the
      compatible solute ectoine. HPLC determinations of the cytoplasmic solute content
      showed the accumulation of a biosynthetic precursor of ectoine, L-2,4
      diaminobutyric acid. Ectoine and hydroxyectoine were not detectable. This mutant
      failed to grow in minimal medium with NaCl concentrations exceeding 4%. However,
      when supplemented with organic osmolytes, the ability to grow in high-salinity
      medium (15% and higher) was regained. We cloned and sequenced the regions
      flanking the transposon insertion in the H. elongata chromosome. Sequence
      comparisons with known proteins revealed significant similarity of the mutated
      gene to the L-2,4-diaminobutyric acid acetyltransferase from the ectoine
      biosynthetic pathway in Marinococcus halophilus. Analysis of a PCR product
      demonstrated that the ectoine biosynthetic genes (ectABC) follow the same order
      as in M. halophilus.

PMID- 9570122
TI  - Edwardsiella tarda induces plasma membrane ruffles on infection of HEp-2 cells.
AB  - Interaction of two clinical Edwardsiella tarda isolates with HEp-2 cells was
      investigated. By electron microscopy we observed at 1 h post infection that E.
      tarda induced formation of extensive plasma membrane projections resembling
      membrane ruffles. The ruffles did not coincide with adhering bacteria. Only few
      invading bacteria were seen. Vacuolated nuclear membrane was occasionally
      observed. Three hours post infection, E. tarda induced a contact-dependent cell
      lysis, revealing the host cell cytoskeleton and nucleus. Only one of the E. tarda
      strains was seen residing within the host cell remains. The results indicate that
      E. tarda-induced membrane ruffles may involve a distinct mechanism of bacterial
      pathogenesis.

PMID- 9570123
TI  - Expression of membrane-associated proteins by strains of enteroaggregative
      Escherichia coli.
AB  - Certain strains of enteroaggregative Escherichia coli express an outer membrane
      associated protein, involved with the adhesion of these bacteria to HEp-2 cells.
      Strains of enteroaggregative E. coli hybridising with DNA probes for aggregative
      adhesion, diffuse adhesion and aggregative adhesion fimbriac II expressed an
      outer membrane-associated protein of 18 kDa regulated by magnesium ions. Strains
      hybridising with the aggregative adhesion probe only expressed a 20-kDa outer
      membrane-associated protein regulated by calcium and magnesium. The present study
      describes two populations of enteroaggregative E. coli which appear to adhere to
      HEp-2 cells by expressing antigenically distinct, negatively charged membrane
      associated proteins.

PMID- 9570124
TI  - Molecular analyses of glucosyltransferase genes among strains of Streptococcus
      mutans.
AB  - Three glucosyltransferase (GTase) genes (gtfB, gtfC and gtfD) were cloned and
      sequenced from clinically isolated strains of Streptococcus mutans MT8148
      (serotype c), MT4239 (c), MT4245 (e), MT4467 (e) and MT4251 (f), respectively.
      Comparison of the gtf genes revealed that interstrain difference of gtfB and gtfD
      was limited, while gtfC showed significant interstrain variations. Similar to
      gtfB and gtfD, gtfC possessed five direct repeats composed of homologous unit in
      the carboxyl-terminal portion. The repeating unit consisted of 63-65 amino acid
      residues and is responsible for glucan binding. The gtfC gene from S. mutans
      MT4245 lacked the fourth unit. Multiple alignment with the gtf sequence of strain
      GS-5 (c) revealed several changes in these gtf genes due to frameshift mutations.
      The peptides encoded by the gtfB, gtfC and gtfD genes of GS-5 were 1, 80, and 32
      amino acid residues shorter than those of the test strains except strain MT4245.

PMID- 9570125
TI  - Isolation and heterologous expression of a gene encoding 4-hydroxyphenylpyruvate
      dioxygenase from the wheat leaf-spot pathogen, Mycosphaerella graminicola.
AB  - We describe the isolation and sequence of a gene encoding 4-hydroxyphenylpyruvate
      dioxygenase (HPPD) (EC 1.13.11.27)) from the wheat leaf-spot fungal pathogen
      Mycosphaerella graminicola (Septoria tritici), that directs the synthesis of 2,5
      dihydroxyphenylacetate (homogentisic acid, HGA). The sequence of the deduced
      peptide showed homology to HPPDs from other organisms; the greatest identity was
      to a T-cell reactive protein, also identified as HPPD, from the human fungal
      pathogen Coccidioides immitis. As observed for HPPD from other sources,
      expression of the M. graminicola HPPD gene in Escherichia coli cells could be
      detected by the gradual development of a brown pigment in cultures as a result of
      the spontaneous oxidation and polymerisation of HGA. Pigment development in these
      cultures was prevented by the HPPD inhibitor sulcotrione.

PMID- 9570126
TI  - Transcription of multiple cell wall protein-encoding genes in Saccharomyces
      cerevisiae is differentially regulated during the cell cycle.
AB  - The yeast cell wall consists of an internal skeletal layer and an outside protein
      layer. The synthesis of both beta-1,3-glucan and chitin, which together from the
      cell wall skeleton, is cell cycle-regulated. We show here that the expression of
      five cell wall protein-encoding genes (CWP1, CWP2, SED1, TIP1 and TIR1) is also
      cell cycle-regulated. TIP1 is expressed in G1 phase, CWP1, CWP2 and TIR1 are
      expressed in S/G2 phase, and SED1 in M phase. The data suggest that these
      proteins fulfil distinct functions in the cell wall.

PMID- 9570127
TI  - Identification of the mgc1 mutation which affects mating-pheromone-induced
      morphogenesis in the yeast Saccharomyces cerevisiae.
AB  - Cells of the yeast Saccharomyces cerevisiae undergo morphogenesis in response to
      the mating pheromones a- and alpha-factors. The 'shmoo' morphology involves
      localized cell surface projection formation and cytoskeleton protein synthesis.
      This polarization is presumed to be a prelude to mating between mating partners
      with opposite mating types, a and alpha. To identify genes involved in pheromone
      induced morphogenesis, a system in which a gpa1 fus3 double mutant was used as a
      parent strain was developed, and mutants which showed altered morphogenesis in
      response to mating pheromone were identified. The mutation was designated mgc1
      for morphogenesis control by mating pheromones. The mgc1 mutant arrested cell
      division in response to alpha-factor and mated with cells of the opposite mating
      type, but did not form a typical projection in response to pheromones.

PMID- 9570128
TI  - Corrigendum to 'Purification and characterization of a monomeric isocitrate
      dehydrogenase from the sulfate-reducing bacterium Desulfobacter vibrioformis and
      demonstration of the presence of a monomeric enzyme in other bacteria' [FEMS
      Microbiol. Lett. 160 (1998) 75-79].

PMID- 9570129
TI  - Transcription factors: an overview.
AB  - This special issue of the International Journal of Biochemistry and Cell Biology
      contains a series of review articles and original papers dealing with the topic
      of transcription factors. The purpose of this introductory article is to provide
      an overview of these factors, their mechanism of action, their regulation and the
      manner in which alterations in them can result in disease.

PMID- 9570130
TI  - Transcriptional regulation by the Sp family proteins.
AB  - Sp1 is one of the very first cellular transcription factors to be identified and
      cloned in virtue of its binding to a G-rich motif in the SV40 early promoter. Sp1
      protein binds to the G-rich sequences present in a variety of cellular and viral
      promoters and stimulates their transcriptional activity. Recently, a number of
      other GC and/or GT box-binding factors homologous to Sp1 have been isolated,
      namely Sp2, Sp3 and Sp4, and the two more distantly related factors, BTEB and
      BTEB2. The discovery of this family highlights a previously unknown level of
      complexity of transcriptional regulation of promoters containing GC and/or GT box
      motifs. This review focuses primarily on strategies aimed to elucidate the
      transcription properties of the Sp1-like factors and discusses the experimental
      problems inherent in the attempt to define their respective functions.

PMID- 9570131
TI  - Nuclear receptors: structure, function and involvement in disease.
AB  - Nuclear hormone receptors are acting as transcription factors in the cell
      nucleus. They regulate gene expression of hormonal regulated target genes. The
      role of hormone in the transcriptional process is to modulate and change the
      nuclear receptor functionality. Receptors contain a DNA binding domain that
      enables them to bind to hormone response elements of target genes. Nuclear
      hormone receptors bind to lipophilic hormones produced by the organisms'
      endocrine system, which links the secretion of hormones directly to regulation of
      gene expression of responsive tissues. In recent years increasing numbers of
      naturally occurring mutations of a variety of nuclear hormone receptor genes were
      identified in patients showing abnormalities in hormonal response. Here, we
      present an overview of nuclear receptors and their mutant forms which cause human
      syndromes or are associated with cancer progression. The major scope of this
      article is to give an overview on the structural-functional relationship and
      based on that, to understand the effects of naturally occurring receptor mutants
      on the molecular level. Thereby, functional aberrations of naturally occurring
      receptors for androgen, glucocorticoids, mineralocorticoid, estrogen, vitamin D3,
      retinoic acid, and thyroid hormone as well as the orphan receptor DAX1 are
      discussed.

PMID- 9570132
TI  - The estrogen receptor gene: promoter organization and expression.
AB  - The estrogen receptor (ER) is a ligand-activated transcription factor and a
      member of a large family of nuclear hormone receptors. As a mediator of estrogen
      hormone action, the ER is involved in many important physiological processes. ER
      gene expression has been demonstrated to be restricted to certain tissues and
      under complex hormonal control. However, the molecular mechanisms involved have
      remained largely unknown. Due to this lack of knowledge an investigation was
      undertaken to characterize the promoter organization of ER gene and investigate
      its expression. Approximately 3 kb of the 5' flanking region of the human ER
      (hER) gene was isolated and sequenced. By performing RT-PCR and RACE experiments
      it was shown that the hER gene is transcribed from three different promoters.
      Transcription of the hER gene from these promoters yields three different mRNA
      isoforms with unique 5' untranslated regions (5'UTRs), but identical coding
      regions. The expression pattern of the hER mRNA isoforms was investigated by RT
      PCR. Both the A- and B-mRNA isoforms were found to be expressed in breast and
      uterus, whereas expression of the C-transcript was predominantly detected in
      liver. In bone cells only expression of the B-mRNA could be detected. The steady
      state levels of the A- and B-transcripts in normal breast and uterus were
      quantified and compared with the hER mRNA levels in established cancer cell lines
      derived from the same tissues. This demonstrated approximately equal levels of
      the two transcripts in normal tissues whereas the A-mRNA was the most abundant
      isoform in the cancer cell lines investigated. Approximately 4.5 kb of the 5'
      flanking region of the rat ER (rER) gene were sequenced. Sequence analysis and
      PCR experiments suggested that the promoter organization of the rat and human ER
      genes is only partially conserved which might indicate species-specific
      differences in the regulation of ER expression. In conclusion, this work suggests
      tissue-specific alternative promoter usage as a mechanism in the regulation of
      human and rat ER gene expression.

PMID- 9570133
TI  - The ETS-domain transcription factor family.
AB  - During recent years, several significant discoveries have been made concerning
      the function of ETS-domain transcription factors. This family of transcription
      factors was originally defined on the basis of the conserved primary sequence of
      their DNA-binding domains. The ETS DNA-binding domain is also conserved at the
      structural level and is a divergent member of the winged helix-turn-helix
      superfamily of DNA binding proteins. This sequence conservation is reflected by
      their overlapping DNA-binding specificities based on the central GGAA/T motif. In
      addition to DNA-protein interactions, protein-protein interactions with partner
      proteins often play major roles in targeting ETS-domain proteins to specific
      promoters. Several such partner proteins have been identified. ETS-domain
      proteins function as either transcriptional activators or repressors and their
      activities are often regulated by signal transduction pathways, including the MAP
      kinase pathways. Specific links between such pathways and ETS-domain proteins
      have been established in several different experimental systems. ETS-domain
      transcription factors regulate a diverse array of biological functions including
      mammalian haematopoiesis and Drosophila eye development. In vertebrates, many ETS
      domain proteins regulate embryonic and adult haematopoiesis. Deregulation of ETS
      domain protein activity often leads to tumorigenesis. Future work will uncover
      further details of how these transcription factors work at the molecular level to
      regulate specific biological processes.

PMID- 9570134
TI  - bHLH transcription factors and mammalian neuronal differentiation.
AB  - The basic helix-loop-helix (bHLH) factor Mash1 is expressed in the developing
      nervous system. Null mutation of Mash1 results in loss of olfactory and autonomic
      neurons and delays differentiation of retinal neurons, indicating that Mash1
      promotes neuronal differentiation. Other bHLH genes, Math/NeuroD/Neurogenin, all
      expressed in the developing nervous system, have also been suggested to promote
      neuronal differentiation. In contrast, another bHLH factor, HES1, which is
      expressed by neural precursor cells but not by neurons, represses Mash1
      expression and antagonizes Mash1 activity in a dominant negative manner. Forced
      expression of HES1 in precursor cells blocks neuronal differentiation in the
      brain and retina, indicating that HES1 is a negative regulator of neuronal
      differentiation. Conversely, null mutation of HES1 up-regulates Mash1 expression,
      accelerates neuronal differentiation, and causes severe defects of the brain and
      eyes. Thus, HES1 regulates brain and eye morphogenesis by inhibiting premature
      neuronal differentiation, and the down-regulation of HES1 expression at the right
      time is required for normal development of the nervous system. Interestingly,
      HES1 can repress its own expression by binding to its promoter, suggesting that
      negative autoregulation may contribute to down-regulation of HES1 expression
      during neural development. Recent studies indicate that HES1 expression is also
      controlled by RBP-J, a mammalian homologue of Suppressor of Hairless [Su(H)], and
      Notch, a key membrane protein that may regulate lateral specification through RBP
      J during neural development. Thus, the Notch-->RBP-J-->HES1-Mash1 pathway may
      play a critical role in neuronal differentiation.

PMID- 9570135
TI  - IL-6-regulated transcription factors.
AB  - Through the cloning of two transcription factors named NF-IL6 and STAT3/APRF, two
      types of IL-6 signal transduction pathways from the cell surface to the nucleus
      have been revealed. NF-IL6 is phosphorylated and activated by a Ras-dependent MAP
      kinase cascade, while STAT3/APRF is directly tyrosine-phosphorylated by JAK
      kinases that associate with the cytoplasmic portion of the receptor, and
      translocates to the nucleus and activates transcription (JAK-STAT pathway). STAT3
      is also tyrosine phosphorylated in response to epidermal growth factor (EGF),
      granulocyte colony-stimulating factor (G-CSF), leptin and other IL-6-type
      cytokines including ciliary neurotrophic factor (CNTF), oncostatin M and leukemia
      inhibitory factor (LIF). Mice deficient in the genes for NF-IL6 and STAT3 were
      generated. NF-IL6 mice were highly susceptible to facultative intracellular
      bacteria owing to ineffective killing of the pathogens by the macrophages.
      Futhermore, the tumor cytotoxicity of macrophages from NF-IL6 KO mice was
      severely impaired. These results demonstrate a crucial role of NF-IL6 in
      macrophage bactericidal and tumoricidal activities. The target disruption of
      STAT3 resulted in embryonic lethality prior to gastrulation, demonstrating that
      STAT3 is essential for the early development of mouse embryos.

PMID- 9570136
TI  - Mammalian oxygen sensing and hypoxia inducible factor-1.

PMID- 9570137
TI  - Achieving transcriptional specificity with NF-kappa B.
AB  - Nuclear Factor-Kappa B (NF-kappa B) was first identified by Sen and Baltimore
      (1986, Cell 46, 705-716) as a constitutively active transcription factor binding
      the kappa light chain immunoglobulin enhancer in B cells. Shortly afterwards, the
      same researchers found NF-kappa B to be present in other cell types in an
      inactive cytoplasmic form which upon cellular stimulation could be induced to
      translocate to the nucleus and bind DNA. Subsequently, it has been demonstrated
      that NF-kappa B performs a critical role as a regulator of the immune system, the
      response to stress, apoptosis, viral replication and is involved in many
      diseases, leading to it becoming one of the most intensively studied
      transcription factors of the last decade. The pivotal role played by NF-kappa B
      is illustrated not only by the great diversity of genes that it regulates, but
      also by the large variety of stimuli leading to its activation. This article will
      address how NF-kappa B, a ubiquitously expressed transcription factor composed of
      dimers formed from five subunits, differentially regulates the expression of such
      a diverse array of genes with different functions, in different cell types and at
      different times. Recent research indicates that this behavioral diversity arises
      from a delicately balanced network of protein: protein interactions: NF-kappa B
      activity is determined not only through its regulated nuclear localization but is
      also dependent on the cellular context in which it is found.

PMID- 9570138
TI  - Chromosomal translocations involving paired box transcription factors in human
      cancer.
AB  - The PAX genes encode a family of transcription factors that control development
      within the neural, myogenic, lymphoid, and a variety of other lineages. These
      proteins are postulated to regulate expression of gene products that function in
      the control of cellular processes are fundamental to the development of cancer,
      and thus genetic alterations of these genes may contribute to neoplastic
      development within these lineages. In support of this premise, several PAX genes
      have been shown to be targets of consistent chromosomal translocations associated
      with specific tumor types. The t(2;13) and t(1;13) translocations associated with
      the myogenic soft tissue cancer alveolar rhabdomyosarcoma fuse portions of the
      PAX3 or PAX7 gene with a portion of the FKHR gene to generate novel fusion
      proteins. The t(9;14) translocation associated with the B cell tumor
      lymphoplasmacytoid lymphoma juxtaposes the PAX5 gene into the vicinity of the IGH
      locus to deregulate PAX5 expression. This review will examine the molecular basis
      of these translocations and the role of altered function or expression of paired
      box transcription factors in the process of tumorigenesis.

PMID- 9570139
TI  - Histone H1.
AB  - Linker histones of which histone H1 is a representative are a diverse family of
      architectural proteins within the eukaryotic nucleus. These proteins have a
      variety of structures, but invariably contain a region enriched in lysine,
      serine, alanine and proline. All metazoan histone H1s also include a structured
      domain that binds to DNA through a helix-turn-helix motif. By binding to the
      linker DNA flanking the nucleosome core they contribute to the assembly of higher
      order chromatin structures. Surprisingly, the use of "knockout" technology to
      eliminate histone H1 in isolated cells and Xenopus does not prevent the assembly
      of chromosomes or nuclei, however specific genes are activated or repressed
      indicative of targeted regulatory functions. A dual role for histone H1 in
      chromatin structure and gene regulation might contribute to epigenetic phenomena
      in which heritable states of gene activity are maintained through mechanisms
      independent of gene sequence. This may have important implications for
      biotechnological and medical research.

PMID- 9570140
TI  - Myocyte enhancer factor 2 (MEF2).
AB  - The Myocyte Enhancer Factor 2 (MEF2) proteins are transcription factors expressed
      during development of all three muscle lineages. Of the four mammalian mef2
      genes, three (A, C and D) can be alternatively spliced, producing transcripts and
      proteins which may have significant functional differences. Specific binding
      sites for MEF2 proteins have been characterized in many striated muscle genes and
      MEF2 proteins can trans-activate gene expression both as homo- and heterodimers.
      Loss-of-function mutants in Drosophila indicate that MEF2 is an essential co
      factor, but not a primary determinent, in the development of all three muscle
      lineages in the fly. Recent data suggest an interaction between the DNA-binding
      domains of mammalian MEF2 proteins and those of tissue-specific basic helix-loop
      helix (bHLH) factors and thyroid hormone receptor alpha 1 (TR alpha 1) in the
      expression of target genes and the development of specific cell phenotypes.
      Understanding how MEF2 proteins function in the three mammalian muscle types may
      allow the development of therapeutic strategies for manipulating muscle growth
      and characteristics.

PMID- 9570141
TI  - Thyroid transcription factor-1.
AB  - Thyroid transcription factor-1 (TTF-1) is a recently identified member of the
      homeodomain transcription factor family, which plays a role in regulating genes
      expressed within the thyroid, lung and brain, including thyroglobulin, thyroid
      peroxidase, Clara cell secretory protein and the surfactant proteins. Additional
      studies, including gene targeting experiments, have clearly shown that expression
      of TTF-1 is essential for morphogenesis of the thyroid, lung and ventral
      forebrain, as TTF-1 knockout mice lack these organs. In the light of these
      studies it seems possible that mutations in TTF-1 may underlie certain
      abnormalities either of organogenesis of, or of cellular function within, these
      organ systems. A recent example of such a defect is the identification of a
      patient with thyroglobulin deficiency due to decreased TTF-1 expression.

PMID- 9570142
TI  - The effect of a nested set of C-terminal substituted deletions on the function of
      the alpha subunit of Escherichia coli RNA polymerase.
AB  - A genetic screen was devised to obtain plasmid-borne rpoA alleles exhibiting
      partial or no complementation of the chromosomal Escherichia coli rpoA341 allele
      responsible for a pleiotropic phenotype. Nine of the ten mutants obtained carried
      single base pair deletions within the 3' end of rpoA resulting in frameshifting
      into a 72 codon +1 orf extending from within codon L262 and terminating 16 bp
      downstream of the rpoA reading frame. These frameshifts give rise to a set of
      substituted alpha deletions that are all of the same size (334 aa) and carry
      segments of the Orf sequence replacing the alpha region from the C-terminus
      (residue 329) to various points between 272 > 319. The in vivo properties of this
      nested set of nine C-terminal-substituted derivatives of the alpha subunit of RNA
      polymerase have been assessed in terms of their assembly and transcriptional
      proficiency. The results indicate: (i) replacement of as much as 42 C-terminal
      residues of the alpha subunit does not prevent formation of a transcriptionally
      proficient holoenzyme form of RNA polymerase capable of complementing
      rpoA112(Ts); (ii) the extreme C-terminal Orf region, like that of alpha itself,
      is exposed in holoenzyme; (iii) these substituted deletions are not commonly
      functional at class I activated promoters.

PMID- 9570143
TI  - DNA-dependent RNA polymerase from Enterobacter cloacae is closely related to
      Escherichia coli.
AB  - The RNA polymerase holoenzyme (RNAP) of Enterobacter cloacae was purified by gel
      filtration and heparin affinity chromatography and shown to consist of four
      subunits (beta', beta, alpha and sigma) of 156, 151, 45 and 82 kDa, as measured
      by SDS-PAGE. The 82 kDa protein was shown to be related to the Escherichia coli
      primary sigma factor by western blot analysis with polyclonal antisera raised
      against purified E. coli sigma 70. Functional reconstitution of E. cloacae core
      enzyme with purified E. coli sigma 70 showed that E. cloacae and E. coli sigma
      factors are closely related. The RNAP of E. cloacae initiated transcription from
      the tac promoter with an efficiency similar to that of E. coli. Measuring
      promoter-specific transcription, the dependence of holoenzyme activity on salt,
      divalent cation and temperature was also similar to that of the E. coli RNAP. We
      also showed that the transcriptional inhibitor, rifampicin, inhibits the enzyme
      activity of the purified RNAP of E. cloacae and E. coli at similar
      concentrations. We conclude, based on these data, that the RNAP of E. cloacae and
      E. coli, both enterobacteria, are closely related.

PMID- 9570144
TI  - Regulation of the serine proteinase inhibitor (SERPIN) gene alpha 1-antitrypsin:
      a paradigm for other SERPINs.
AB  - alpha 1-antitrypsin (AAT) is the archetypal member of the serine proteinase
      inhibitor (SERPIN) gene family. AAT is an acute-phase reactant and the plasma
      concentration increases three- to four-fold during the inflammatory response. In
      hepatocytes this increase is mediated primarily by the cytokine interleukin-6 (IL
      6) via the transcription factor NF-IL6. The AAT gene contains at least two
      enhancer elements, one at the 5' end of the gene and the other at the 3' end.
      Functional studies performed in mammalian hepatoma cells (Hep G2) using
      constructs containing these AAT enhancer regions linked to a reporter gene have
      demonstrated that the 5' enhancer is dominant under basal conditions and that,
      following stimulation with IL-6, both enhancers are essential and the 3' enhancer
      plays a major role. We have identified a mutation associated with lung disease
      which occurs in the 3' AAT enhancer; the mutation occurs at a binding site for
      the ubiquitous transcription factor Oct-1. The functional significance of this
      mutation is a deficient IL-6 response. Using the AAT gene as a model, we describe
      the interactions which occur between transcription factors within the 3' enhancer
      and also those which take place between the 5' and 3' enhancers. These studies
      shed light on the molecular mechanism of the acute-phase response which could
      possibly be extended to other members of the SERPIN gene family.

PMID- 9570145
TI  - Steroidogenic factor-1 (SF-1) and the regulation of expression of luteinising
      hormone and follicle stimulating hormone b-subunits in the sheep anterior
      pituitary in vivo.
AB  - Luteinising hormone (LH) and follicle stimulating hormone (FSH) comprise a common
      alpha-subunit and hormone-specific beta-subunit, are expressed in gonadotroph
      cells of the anterior pituitary and during the sheep oestrous cycle, are
      regulated by gonadotrophin releasing hormone (GnRH), ovarian peptides and
      steroids. Transcription factor steroidogenic factor-1 (SF-1) transactivates the
      common alpha-subunit and LH beta subunit in other species. We investigated
      whether SF-1 regulates beta-subunit expression and the regulation of SF-1
      expression in vivo in sheep. Immunocytochemistry co-localised SF-1, LH and FSH to
      sheep pituitary gonadotrophs and electrophoretic mobility shift assays (EMSA)
      demonstrated that SF-1 bound to the LH beta promoter in vitro. No SF-1 DNA
      binding site was found in the FSH beta promoter. No difference in mean levels of
      SF-1, FSH beta, LH beta and GnRHr mRNA was measured between the luteal and
      follicular phases of the oestrous cycle. However SF-1 mRNA levels were correlated
      to those of LH beta in individual luteal phase animals (r = 0.88, p < 0.05), when
      the transcription rate of LH beta was significantly higher (p < 0.01). GnRH
      antagonist treatment of luteal animals did not produce a significant reduction in
      mRNA levels of LH beta, SF-1 and FSH beta. Administering oestradiol benzoate with
      GnRH antagonist reduced levels of SF-1 and FSH beta mRNA from luteal values (p <
      0.005). We conclude that: (1) expression of SF-1 is not solely dependent on GnRH
      and is downregulated by oestradiol; (2) the LH beta transcription rate is
      increased during the luteal phase but is not related to levels of LH beta or SF-1
      mRNA; and (3) SF-1 does not appear to directly regulate expression of FSH beta,
      but may regulate expression indirectly.

PMID- 9570146
TI  - Cross-talk between transcription factors NF-kappa B and C/EBP in the
      transcriptional regulation of genes.
AB  - The study of the acute phase response has attracted substantial interest, not
      only for its medical implication, but also its provision as an excellent system
      with which to elucidate the molecular mechanisms involved in the modulation of
      gene expression. Our previous data suggest that the synergistic induction of the
      major acute phase reactant serum amyloid A2 (SAA2) expression by interleukin-1
      (IL-1) and interleukin-6 (IL-6) is mediated by two families of transcription
      factors, namely NF-kappa B and C/EBP. To understand the molecular mechanisms of
      this synergy, we have undertaken a molecular dissection of the factors involved
      in the formation of the regulatory complex. Electrophoretic mobility shift
      analysis indicates that NF-kappa B p65 (RelA) and p50, but not p52 or c-Rel, bind
      specifically to the NF-kappa B site of the SAA2 promoter in response to IL-1
      stimulation. In addition, C/EBP beta and C/EBP delta, but not C/EBP alpha, bind
      specifically to the C/EBP site of SAA2 in response to IL-6 stimulation. Transient
      co-transfection analysis indicates that co-operative association of NF-kappa B
      p65 with C/EBP beta and, in particular, with C/EBP delta, results in synergistic
      transcriptional activation of the SAA2 promoter. When incubated together, NF
      kappa B p65 and C/EBP beta form a ternary complex by direct protein/protein
      interaction. Mutational analysis demonstrates that the C-terminus region of the
      Rel homology domain (RHD) and the C-terminus of the activation domain of p65 are
      important for its interaction with C/EBP beta. These results suggest the NF-kappa
      B and C/EBP may form a new complex of transcription factors that mediates the
      synergistic induction of SAA2 by IL-1 and IL-6.

PMID- 9570148
TI  - Rapid method for isolation of total RNA from eukaryotic cell lines and
      leukocytes.
AB  - Total RNA was isolated from human leukocytes (monocytes, granulocytes), various
      cell lines (COS-7, Mono-Mac-6, L-132, HaCaT, EA.hy926, HL-60), and fungal
      mycelium by a rapid two-step method. Cells were lysed with NaDodSO4 in a citric
      acid-containing buffer. This procedure was succeeded by salt precipitation to
      remove contaminating DNA and protein and a final alcohol precipitation of RNA.
      Isolated RNA was of high quality, with a reasonable yield and little or no
      protein or DNA contamination. We present here a fast method for preparing RNA
      particularly from cell lines, which limits the use of toxic compounds.

PMID- 9570147
TI  - Cloning, sequence analysis, and distribution of rat metallocarboxypeptidase Z.
AB  - A cDNA encoding human carboxypeptidase Z (CPZ), a novel metallocarboxypeptidase,
      was recently cloned (Song and Fricker, J. Biol. Chem., 272, 1054, 1997). In the
      present study, a cDNA encoding the rat homolog of CPZ was identified. As with the
      human form, rat CPZ contains an N-terminal domain of 120 amino acids that has 20%
      to 30% amino acid identity with the "frizzled" domain found on proteins that
      interact with Wnt, a protein involved in tissue polarity in early embryogenesis.
      Sequence analysis showed rat and human CPZ to be highly conserved within the
      frizzled domain (77% amino acid identity), the carboxypeptidase domain (91%), and
      the C-terminal 28 residues (78%). The entire rat CPZ protein has high sequence
      similarity with human CPZ (81% amino acid identity), moderate sequence similarity
      to human carboxypeptidase N (45%), human carboxypeptidase E (41%), and human
      carboxypeptidase M (33%), and less sequence similarity with other
      metallocarboxypeptidases. Northern blot analysis showed rat CPZ mRNA to be
      abundant in the placenta, with low to moderate levels in the brain, lung, thymus,
      and kidney. The BRL3A rat liver cell line and the PC12 rat adrenal cell line
      express high levels of CPZ mRNA. In situ hybridization analysis indicated that
      CPZ is expressed only in specific cell types. For example, in the brain, CPZ mRNA
      is present in leptomeningeal cells, but not in the majority of other cell types.
      This distribution in leptomeningeal cells is shared by AEBP1, a recently reported
      member of the metallocarboxypeptidase gene family. However, the distribution of
      CPZ and AEBP1 differ in pituitary and thyroid. Taken together, these studies
      suggest that CPZ functions in a range of cell types.

PMID- 9570149
TI  - Detection of protein-DNA interactions at beta-globin gene cluster in intact human
      cells utilizing hedamycin as DNA-damaging agent.
AB  - The DNA sequence specificity of hedamycin (HDM) damage was investigated in the
      single-copy human beta-globin gene cluster in an erythroid cell line, a
      nonerythroid cell line, and purified genomic DNA. The target DNA sequences for
      this study were the beta-globin gene locus control region (LCR) hypersensitive
      site 2 (HS-2) and the beta-globin gene promoter. The DNA fragments produced by
      HDM damage in these target sequences were selectively amplified by the ligation
      mediated polymerase chain reaction (LMPCR) and analyzed at nucleotide resolution
      by DNA-sequencing gel electrophoresis. The DNA sequences damaged by HDM in the
      cellular environment were found to be similar to that observed in the purified
      genomic DNA. However, substantial differences did occur between the intensity of
      cellular and purified genomic DNA reaction products at discrete regions
      corresponding to transcription factor-binding motifs. This was most apparent in
      the LCR HS-2 at the tandem NF-E2/AP-1 motif, where the DNA damage activity of HDM
      was severely impaired. This motif has been shown to bind to the erythroid
      specific nuclear factor-erythroid 2 (NF-E2) and the widely distributed activator
      protein-1 (AP-1). The HDM damage protection patterns or "genomic footprints"
      observed at this motif were probably caused by protein-DNA interactions with one
      or both of these transcription factors. This result indicates that the DNA
      damaging activity of HDM in cells is sensitive to bound nuclear factors. Because
      HDM can enter intact cells, where its DNA damaging activity is modulated by
      protein-DNA interactions, it may have application in genomic footprinting
      experiments.

PMID- 9570151
TI  - Inhibitory effect of lipopolysaccharide on immune response after DNA immunization
      is route dependent.
AB  - The DNA prepared from E. coli contained high levels of lipopolysaccharide (LPS).
      When antigen-encoding DNA was injected into mice, toxicity and increased IgM
      responses were observed. A method for purifying high yields of DNA (up to 12 mg/L
      of broth culture) with very low levels of LPS (0.05 ng/mg) was developed. When
      this purified DNA was used for immunization studies, the toxicity and increased
      IgM responses were abrogated. Thus, LPS was added to DNA in order to examine its
      influence on the IgG and cytotoxic T lymphocyte (CTL) response after
      intramuscular (i.m.) or intradermal (i.d.) DNA immunization. The IgG response to
      DNA-encoded antigen was inhibited in a dose-dependent manner by the i.d., but not
      the i.m., route of immunization. Surprisingly, no effect on the CTL response was
      observed. Therefore, the ability to produce high yields of plasmid DNA with very
      low levels of endotoxin contamination is advantageous for DNA immunization
      studies, not only for toxicologic but also for immunologic considerations.
      Furthermore, these results provide further evidence that immune induction occurs
      via different mechanisms after i.m. and i.d. DNA immunization.

PMID- 9570150
TI  - Expression of metastasis-associated genes h-mts1 (S100A4) and nm23 in carcinoma
      of breast is related to disease progression.
AB  - The murine 18A2/mts1 and its human homolog h-mts1 (S100A4), encoding a Ca2+
      binding protein belonging to the S-100 family, are associated with high invasive
      and metastatic potentials of murine tumors, human tumor cell lines in vitro, and
      human tumors growing as xenografts. The nm23 is a putative metastasis-suppressor
      gene whose expression has been found to correlate inversely with the metastatic
      potential of some forms of human cancer. The products of both human genes alter
      cytoskeletal dynamics, with antagonistic effects. In view of the equivocal
      association of nm23 with the metastatic potential of human cancer, we suspected
      that the relative expression of h-mts1 and nm23 might reflect tumor progression
      more accurately than either of them alone. We describe here the expression of
      these genes in infiltrating ductal carcinomas of the breast and show that high h
      mts1 expression is associated with metastatic spread to the regional lymph nodes.
      The expression of nm23 on its own did not show a statistically significant
      inverse correlation with nodal spread. However, the expression status of the two
      genes, taken together, correlated strongly with the occurrence of nodal
      metastases. Breast cancers with no detectable expression of h-mts1 were found to
      be estrogen and progesterone receptor positive. Expression of h-mts1 was not
      related to tumor differentiation. The clinical data, together with the state of
      expression of steroid receptors and the expression levels of h-mts1 and nm23
      genes, were analyzed using artificial neural networks for accuracy in predicting
      nodal spread of the carcinomas. These analyses support the conclusion that,
      overall, h-mts1 expression appears to be associated with and indicative of more
      aggressive disease. Complemented with nm23, h-mts1 could provide a powerful
      marker of breast cancer prognosis.

PMID- 9570152
TI  - Identical cis-acting elements and related trans-acting factors control activity
      of nonviral promoter in Schizosaccharomyces pombe and mammalian cells.
AB  - We have analyzed the transcriptional activity of the human plasminogen activator
      inhibitor-1 promoter in the fission yeast Schizosaccharomyces pombe. This
      promoter is active in S. pombe, and the initiation site of transcription
      corresponds to the site identified previously in mammalian cells. Mutations in
      the AP-1-binding site (PAI-1 A box) or the HLTF-binding site (the B box), which
      reduced the basal and phorbol ester-induced levels of PAI-1 expression in human
      cells, also decreased the transcriptional activity in S. pombe. Gel retardation
      assays showed that an S. pombe protein binds specifically to this B box element
      and displays the same B box sequence requirement as HLTF. Furthermore, this yeast
      protein binds specifically to other HLTF-binding sites in the human
      immunodeficiency virus-1 long terminal repeat (LTR) and the simian virus 40
      (SV40) enhancer. The B box (but not a mutated B box) strongly stimulated
      transcription when combined with adh downstream promoter elements, indicating
      that the S. pombe B box-binding protein, like HLTF, is a transcriptional
      activator. We conclude that the transcriptional activity of the nonviral PAI-1
      promoter is controlled by the same promoter elements in S. pombe as in mammalian
      cells. In addition, mammalian trans-acting factors that bind to these promoter
      elements were shown to have counterparts with conserved DNA-binding activity in
      S. pombe. These results further illustrate the conservation of the mechanism of
      transcription between mammalian cells and fission yeast.

PMID- 9570153
TI  - Isolation and characterization of tilapia (Oreochromis mossambicus) insulin-like
      growth factors gene and proximal promoter region.
AB  - To understand the molecular mechanism which controls the transcription of the
      insulin-like growth factors (IGFs) gene, we have cloned and sequenced the cDNA
      for the proximal promoter region of the tilapia IGFs gene and have characterized
      its activity by chloramphenicol acetyltransferase (CAT) transient transfected
      expression assays. Tilapia (Oreochromis mossambicus) IGF-I cDNA (549 bp) was
      amplified by PCR from single-stranded cDNA of growth hormone (GH)-induced liver
      RNA using a pair of oligonucleotides specific for fish IGF-I as amplification
      primers. Tilapia IGF-I and IGF-II 5' termini were analyzed by rapid amplification
      of cDNA 5' ends (5'RACE). Analysis of the 5'RACE results revealed two
      transcription start sites in IGF-I and one transcription start site in IGF-II.
      Different fragments of the 5' flanking region were transfected into human lung
      adenocarcinoma cells. In the cell line, maximum promoter activity was located in
      the distal 657 basepairs of the IGF-I 5' flanking region and in the distal 450
      basepairs of the IGF-II 5' flanking region. The in vivo actions of the IGFs
      promoter on developmental stage expression were investigated further in
      transgenic zebrafish in which an IGFs promoter-driven green fluorescent protein
      (GFP) encoding the cDNA transgene was microinjected into embryos. Morphologic and
      RT-PCR studies of the transgenic zebrafish indicated that IGF-I promoter-driven
      GFP transcripts appeared for the first time in the 1-K-cell stage and the IGF-II
      promoter-driven GFP transcripts appeared for the first time in the 32-cell stage.
      Fluorescent (GFP) distribution was apparent within 48 h in IGF-II-transgenic
      zebrafish embryos, especially in eye, muscle, corpuscle, floor plate, horizontal
      myoseptum, yolk sac extension, and yolk sac. These results indicate that the IGF
      I and IGF-II promoters are active in tissue and in a development-specific manner.
      Our findings also indicate that the IGF-II promoter influences the growth of fish
      embryos earlier than does IGF-I, and IGF-II has higher levels of expression than
      does IGF-I. These results suggest that the IGF-II promoter plays a growth factor
      role in teleost embryo development.

PMID- 9570154
TI  - Molecular cloning of two alternatively spliced forms of human phosphatidic acid
      phosphatase cDNAs that are differentially expressed in normal and tumor cells.
AB  - Phosphatidic acid (PA) and diacylglycerol (DG) are lipids involved in signal
      transduction and in structural membrane-lipid biosynthesis in cells. Phosphatidic
      acid phosphatase (PAP) catalyzes the conversion of PA to DG. This enzyme exists
      in at least two isoforms, one of which (PAP1) is presumed to be cytosolic and
      membrane associated and the other (PAP2) to be an integral membrane protein.
      Homology search of the GenBank database using a murine sequence probe enabled the
      cloning of several putative human isoenzymes. Two isoforms, presumed to be
      alternative splice variants from a single gene, designated as PAP2-alpha1 and
      PAP2-alpha2, have been cloned and expressed. The PAP2-alpha1 and PAP2-alpha2 have
      a 84% and a 72% overall match, respectively, with the published mouse PAP amino
      acid sequence. The area of alternative exon usage was confined to the coding
      region at amino acids 20 to 70. Ectopic expression of PAP2-alpha1 and PAP2-alpha2
      cDNAs in ECV304 endothelial cells led to a 6- to 8-fold and a 2-fold increase in
      PAP activity, respectively, in cell-free extracts using an in vitro assay that
      measured the conversion of [14C]PA to [14C]DG. The increase in PAP activity in
      PAP2-alpha-transfected cells correlated with a >50% decrease in the steady-state
      PA level. Northern analysis showed that PAP2-alpha mRNA expression was suppressed
      in several tumor tissues, notably those derived from the lower alimentary tract.
      Subsequent analysis of colon tumor tissue derived from four donors confirmed
      lower expression of PAP2-alpha than in matching normal colon tissue. Considering
      these data and previous demonstrations that certain transformed cell lines have
      lower PAP activity, we suggest that human PAP cDNAs may be candidates for gene
      therapy for certain tumors.

PMID- 9570155
TI  - Function of cis-acting elements in human alcohol dehydrogenase 4 (ADH4) promoter
      and role of C/EBP proteins in gene expression.
AB  - The ADH4 gene, which encodes human pi-alcohol dehydrogenase, is expressed in a
      tissue-specific manner, with the highest level in liver and lower levels in the
      gastrointestinal tract. We examined the location and function of the cis-acting
      elements that regulate ADH4 transcription. Liver contains proteins that bound to
      seven sites in the proximal promoter (from bp -387 to bp +17). Proteins from
      other tissues bound to subsets of these sites and to two additional sites, one of
      which is a negative cis-acting element. Members of two important transcription
      factor families, C/EBP and AP-1, bound to several sites in this promoter. The
      proximal ADH4 promoter functioned in a hepatoma cell line (H4IIE-C3) and a kidney
      cell line (CV-1). Coexpression of members of the C/EBP family strongly enhanced
      promoter activity, which can in part explain the high level of expression of ADH4
      in liver. At one site that can be bound by both C/EBP and c-Jun, a mutation that
      abolished binding by C/EBP but not by c-Jun decreased promoter activity in both
      cell lines. This mutation had a stronger effect in the context of a longer
      promoter, suggesting interaction among cis-acting elements.

PMID- 9570156
TI  - SRA's Surface Contamination Monitor.

PMID- 9570157
TI  - Evaluating the risk of death via the hematopoietic syndrome mode for prolonged
      exposure of nuclear workers to radiation delivered at very low rates.
AB  - During a Phase-I effort, studies were planned to evaluate deterministic
      (nonstochastic) effects of chronic exposure of nuclear workers at the Mayak
      atomic complex in the former Soviet Union to relatively high levels (> 0.25 Gy)
      of ionizing radiation. The Mayak complex has been used, since the late 1940's, to
      produce plutonium for nuclear weapons. Workers at Site A of the complex were
      involved in plutonium breeding using nuclear reactors, and some were exposed to
      relatively large doses of gamma rays plus relatively small neutron doses. The
      Weibull normalized-dose model, which has been set up to evaluate the risk of
      specific deterministic effects of combined, continuous exposure of humans to
      alpha, beta, and gamma radiations, is here adapted for chronic exposure to gamma
      rays and neutrons during repeated 6-h work shifts--as occurred for some nuclear
      workers at Site A. Using the adapted model, key conclusions were reached that
      will facilitate a Phase-II study of deterministic effects among Mayak workers.
      These conclusions include the following: (1) neutron doses may be more important
      for Mayak workers than for Japanese A-bomb victims in Hiroshima and can be
      accounted for using an adjusted dose (which accounts for neutron relative
      biological effectiveness); (2) to account for dose-rate effects, normalized dose
      X (a dimensionless fraction of an LD50 or ED50) can be evaluated in terms of an
      adjusted dose; (3) nonlinear dose-response curves for the risk of death via the
      hematopoietic mode can be converted to linear dose-response curves (for low
      levels of risk) using a newly proposed dimensionless dose, D = X(V), in units of
      Oklad (where D is pronounced "deh"), and V is the shape parameter in the Weibull
      model; (4) for X < or = Xo, where Xo is the threshold normalized dose, D = 0; (5)
      unlike absorbed dose, the dose D can be averaged over different Mayak workers in
      order to calculate the average risk of death via the hematopoietic mode for the
      population exposed at Site A; and (6) the expected cases of death via the
      hematopoietic syndrome mode for Mayak workers chronically exposed during work
      shifts at Site A to gamma rays and neutrons can be predicted using ln(2)B M[D];
      where B (pronounced "beh") is the number of workers at risk (criticality accident
      victims excluded); and M[D] is the average (mean) value of D (averaged over the
      worker population at risk, for Site A, for the time period considered). These
      results can be used to facilitate a Phase II study of deterministic radiation
      effects among Mayak workers chronically exposed to gamma rays and neutrons.

PMID- 9570158
TI  - Deposition of charged particles on lung airways.
AB  - The effect of a single electric charge on the efficiency with which ultrafine
      particles deposit in human airways has been investigated. When inhaled short
      lived radon progeny are attached to electrically neutral particles their
      deposition efficiency is controlled by diffusion. But most ambient particles
      carry one, or a few, charges. We measured and compared the deposition (DE) of
      singly charged, charge-neutralized, and zero-charge 20-nm and 125-nm particles in
      hollow-cast models of human airways. These particle sizes were selected because
      they are about where modal peaks occur for the activity of the short-lived radon
      progeny in indoor air. For singly charged 20-nm particles deposition (+/-
      standard error) in the casts was 3.4 +/- 0.3 times that for charge neutralized
      aerosols and 5.3 +/- 0.3 times the amount deposited for zero-charged particles.
      Corresponding ratios for the 125-nm particles were 2.3 +/- 0.3 and 6.2 +/- 0.7.
      Since most ambient particles are charged this effect must be considered when
      models are used to predict dose from inhaled ultrafine particles.

PMID- 9570159
TI  - Blood tritium level as a conservative estimate of soft tissue dose after tritium
      injection in mice.
AB  - The usefulness of the determination of the tritium concentration in blood for
      estimating the average soft tissue dose after tritium intake was tested.
      Tritiated water and a mixture of tritiated amino acids dissolved in saline
      solution were separately administered to adult male mice by intraperitoneal
      injection. The tritium levels in the blood, urine, whole body, spleen, liver,
      testis, and brain were then determined at various periods. With both types of
      tritium administration, the results suggested that the accumulated dose in the
      blood pool gave a conservative estimate of the accumulated dose to the soft
      tissue.

PMID- 9570160
TI  - Diurnal and seasonal variations of radon levels, effects of climatic conditions,
      and radon exposure assessment in a former uranium metal production facility.
AB  - Storage of radon-producing material in two silos and two waste pits is one of the
      major environmental and occupational issues at a former uranium production
      facility, now a Superfund site. In addition, up to 100 metric tons of thorium is
      stored on the northeast side of the site. Concentrations of radium up to 17,600
      Bq g(-1) (477,000 pCi g(-1)) or higher for silos and up to 45 Bq g(-1) (1,200 pCi
      g(-1)) for waste pits have been reported. This study was conducted to identify
      factors and climatic conditions that contribute to higher radon levels and to
      assess workers' exposure at the site. Data covering a 12-mo period were compiled
      from monitoring hourly real-time radon levels at indoor (within 3 buildings) and
      outdoor (at 14 on-site and 2 off-site monitoring stations) locations and from
      hourly site-specific meteorological information. The ranges of radon levels were
      as follows: 1.8-3,655 Bq m(-3) (0.05-98.8 pCi L(-1)) outdoor on-site, 3.7-329 Bq
      m(-3) (0.1-8.9 pCi L(-1)) outdoor off-site, and 1.8-111 Bq m(-3) (0.05-3.0 pCi L(
      1)) indoor on-site. Only radon levels in the vicinity of the storage silos were
      significantly higher than levels off-site. Radon concentrations showed diurnal
      variations, with maximum levels occurring in the early morning and minimum levels
      in the afternoon. Seasonal variation was also observed, with radon levels higher
      during the summer through early fall and lower during the late winter through
      spring. Wind speed, relative humidity, and wind direction appeared to be the most
      significant predictors of radon concentration. The estimated radon dose to
      workers, calculated by using exposure models and annual average levels of radon
      in the work area, was below recommended exposure limits. These results suggest
      that the emission control methods at this site have been effective in maintaining
      environmental radon contamination and workers' exposure at acceptable levels.

PMID- 9570161
TI  - Diffusion model of radon exhalation rates.
AB  - Radon migration through walls is considered using an effective diffusion model.
      One and two dimensional models as well as a spherical geometry are compared. It
      is concluded that either the 1-dimensional or spherical model, both having
      analytical solution, may be used for practical purposes. Application is made for
      typical cases in Athens, Greece.

PMID- 9570162
TI  - Foil coverage of a crawl-space floor: measurements and modeling of radon entry.
AB  - The mitigative impact of covering the floor of a crawl space with a membrane has
      been studied under well-defined and controlled conditions. The measurements have
      been done with a homogeneous column of dry sand covered with a sheet of
      polyethylene foil. An air-filled volume on top of the column simulates a crawl
      space. The experiments mainly concern long-term measurements of the crawl-space
      radon concentration in combination with steady-state diffusive and combined
      advective and diffusive transport through the sand column and crawl space. The
      experimental data are analyzed with both simplified mass-balance models for radon
      entry into the crawl space and with a two-dimensional numerical model based on a
      finite-difference approach. In all experiments the influence of atmospheric
      pressure variations is clearly present. For most experiments the agreement
      between calculations, which make use of independently measured transport
      parameters for both sand and foil, and measurements is within 10%. However, the
      discrepancy is larger for experiments with continuous advective transport from
      the crawl space to the sand. With undamaged foil, the calculations overestimate
      the measurements by 20%. Reversely, with an opening in the center of the foil,
      the calculations underestimate the measurements by 20-40%. The results show that
      under controlled conditions radon transport from a foil-covered sand column into
      a crawl-space can be described within 40% on basis of separately measured
      parameters.

PMID- 9570163
TI  - Comparison of the LLNL and JAERI torso phantoms using Ge detectors and phoswich
      detectors.
AB  - The Human Monitoring Laboratory has compared the LLNL and JAERI torso phantoms
      using its germanium detector lung counting system by measuring the counting
      efficiencies for radioactive materials in the phantoms at photon energies of 17.7
      keV, 59.5 keV, 121.8 keV, and 344 keV to assess the similarity (or differences)
      in performance characteristics. The counting efficiencies obtained from the two
      phantoms were compared by converting the Chest Wall Thickness data and Adipose
      Mass Fractions of the phantoms to Muscle Equivalent Chest Wall Thicknesses. The
      counting efficiencies for the two phantoms were found to be within a factor of
      1.44 of each other at 17.7 keV, 1.30 at 59.5 keV, 1.25 at 121.8 keV, and 1.17 at
      344 keV when using a four detector array (JAERI efficiency divided by LLNL
      efficiency). However, individual detector responses show that the counting
      efficiencies from the two phantoms differ considerably in the region of the heart
      (up to a factor of 6 at 17 keV). Other areas above the lungs give counting
      efficiencies that are similar to each other. A routine intercomparison exercise
      with Cameco Corporation has shown that the counting efficiencies derived from the
      LLNL and JAERI phantoms were found to be within a factor of 1.18 (JAERI/LLNL)
      when a natural uranium lung set was used to calibrate a lung counter consisting
      of phoswich detectors. This work has also shown that over the energy range 63 keV
      185 keV the LLNL phantom can be used to calibrate phoswich detector systems that
      are positioned on the back of the subject.

PMID- 9570165
TI  - Worker dose analysis based on real time dosimetry.
AB  - Real time dosimetry was used to analyze nuclear medicine technologist dose from
      performing positron emission tomography clinical imaging procedures. The purpose
      was to identify which tasks in the procedure were the greatest contributors to
      dose. Results identified the patient positioning task as the single largest
      source of technologist dose, followed by measurement and administration of the
      radioactive drug. The dosimetry method appears suitable for any work situation
      where it is not clear whether task modification or installation of shielding will
      better reduce worker dose.

PMID- 9570164
TI  - Dose-response analyses of osteonecrosis in New Jersey radium workers point to
      roles for other alpha emitters.
AB  - A previous study of 25 radium workers reported radium osteonecrosis to be common
      down to that study's lower limit of detection of 226Ra. This paper reanalyzes
      those data using Poisson and linear regression to obtain quantitative dose
      response estimates for radium osteonecrosis. A quadratic, supralinear response of
      the necrosis ratio to skeletal dose and preterminal 226Ra burden was observed at
      a high level of statistical significance. At low dose the response was linear.
      Clearly observable necrosis, that appearing in 4% of tissue blocks, was seen in
      femurs at approximately 0.8 Gy skeletal dose. Comparable effects from plutonium
      in spongy bone might therefore be expected in the 0.01-0.02 Gy dose range.
      Prediction equations are presented for preterminal 226Ra burden, for skeletal
      dose, and, at low doses where the response can be taken as linear, for dose from
      and uptakes of both 226Ra and 228Ra. Male New Jersey workers in the radium
      refinery were observed to have necrosis not explained by the 226Ra uptakes, but
      compatible with skeletal doses from other internal emitters, in the range 0.25
      1.2 Gy lifetime dose acquired per year of employment. 210Po, inhaled directly or
      from inhaled 210Pb, is the most likely source of this dose.

PMID- 9570166
TI  - 192IrCl acid skin burn: case report and review of the literature.
AB  - A worker was contaminated following a chemical explosion that splashed an HNO3
      radioactive solution containing approximately 180 MBq (5 mCi) 192Ir onto the left
      side of his face. Initial efforts reduced the contamination at least fivefold.
      Removal of a patch of contaminated hair was necessary. Most of the contamination
      was fixed to the skin; only a small amount of contamination was absorbed.

PMID- 9570167
TI  - A joint HML-KAERI project--comparison of the LLNL and JAERI torso phantoms using
      four 50 mm Ge detectors.
AB  - The Health Physics Department of the Korea Atomic Energy Research Institute and
      the Human Monitoring Laboratory have collaborated to compare the LLNL and JAERI
      torso phantoms. The counting efficiencies of the phantoms at 17.7 keV, 59.5 keV,
      121.8 keV, and 344 keV were measured with KAERI's germanium lung counting system.
      The data were made comparable by converting the chest wall thicknesses and
      adipose mass fractions of the phantoms to muscle equivalent chest wall
      thicknesses. The counting efficiencies of the two phantoms are within 12% to 17%
      of each other at 17.7 keV, 15% to 22% at 59.5 keV, 10% to 15% at 121.8 keV, and
      7% to 10% at 344 keV. This joint study has shown that the LLNL and JAERI phantom
      are essentially equivalent for the purposes of calibrating a lung counting system
      that consists of two ACTII germanium detectors.

PMID- 9570168
TI  - The effect of managed care on quality: a review of recent evidence.
AB  - This article reviews recent evidence about the relationship between managed care
      and quality. With one exception, the studies reviewed represent observation
      periods that extend through 1990 or a more recent year. The review has led to the
      conclusion that managed care has not decreased the overall effectiveness of care.
      However, evidence suggests that managed care may adversely affect the health of
      some vulnerable subpopulations. Evidence also suggests that enrollees in managed
      care plans are less satisfied with their care and have more problems accessing
      specialized services. In addition, younger, wealthier, and healthier persons were
      more satisfied with their health plans than older, poorer, and sicker persons,
      even after adjusting for the type of health plan.The findings of the studies
      reviewed do not provide definitive results about the effect of managed care on
      quality. Indeed, relatively few studies include data from the 1990s, and little
      is known about the newer types of health maintenance organizations that invest
      heavily in information systems and rely on financial incentives to alter practice
      patterns. Furthermore, managed care is not a uniform method that is applied
      identically by all health plans, and research studying the different dimensions
      of managed care also is needed.

PMID- 9570169
TI  - Treatment of Helicobacter pylori infection.
AB  - Since acceptance of the association between Helicobacter pylori and peptic ulcer
      disease, eradication of H. pylori has become the standard of care in the
      treatment of peptic ulcer disease. Unfortunately, eradication therapy is no easy
      task, especially when one is faced with a myriad of drug combinations with
      varying degrees of efficacy and tolerability. The following is a review of the
      literature regarding the drugs and drug combinations used to eradicate H. pylori
      and their effectiveness both as single agents and in combination.

PMID- 9570170
TI  - Cost savings in duodenal ulcer therapy through Helicobacter pylori eradication
      compared with conventional therapies: results of a randomized, double-blind,
      multicenter trial. Gastrointestinal Utilization Trial Study Group.
AB  - BACKGROUND: We hypothesized that treatment of duodenal ulcer disease with
      antibiotic therapy directed toward Helicobacter pylori infection is more cost
      effective than therapy with antisecretory agents. METHODS: A randomized, double
      blind, multicenter clinical trial of adult patients with active duodenal ulcer
      and H. pylori infection was conducted. Patients were randomized to receive 500 mg
      of clarithromycin 3 times a day plus 40 mg of omeprazole daily for 14 days
      followed by 20 mg of omeprazole daily for an additional 14 days (group 1), 20 mg
      of omeprazole daily for 28 days (group 2), or 150 mg of ranitidine hydrochloride
      twice a day for 28 days (group 3). The use of ulcer-related health care resources
      was documented during monthly interviews for 1 year after the initial therapy.
      Clinical success was evaluated 4 to 6 weeks and 1 year after the end of therapy.
      RESULTS: Of the 819 patients enrolled, 727 completed the study. Group 1 included
      243 patients; group 2, 248 patients; and group 3, 236 patients. Patients in group
      1 used fewer ulcer-related health care resources during the 1 year after therapy
      compared with groups 2 and 3 (comparisons are given as group 1 vs group 2 and
      group 1 vs group 3, respectively): the number of endoscopies performed, 28 vs 76
      (P<.001) and vs 71 (P<.001); patients receiving drugs to treat an ulcer, 118 vs
      180 (P<.001) and vs 168 (P<.001); clinic visits, 83 vs 135 (P=.05) and vs 161
      (P<.001); hospitalizations, 0 vs 5 (P=.045) and vs 6 (P=.02); and length of
      hospital stay, 0 vs 24 days (P=.04) and vs 37 (P=.04). When ulcer-related costs
      were defined as the outcome variable in a multivariate linear regression
      analysis, therapy was determined to have a significant influence on costs (group
      1 vs group 2, P<.001; group 1 vs group 3, P=.008). Clinical success rates at the
      end of the study and cure of H. pylori infection were significantly greater in
      group 1 compared with groups 2 and 3 (P<.001). Therapy with clarithromycin plus
      omeprazole provided savings of $1.94 and $2.96 (compared with therapy with
      omeprazole and with ranitidine hydrochloride, respectively) per dollar spent
      within the first year after therapy. This incremental cost-benefit translates to
      savings of $547 or $835 per patient in group 1 (compared with patients in group 2
      or group 3, respectively) during the first year after therapy. CONCLUSIONS:
      Combination therapy with clarithromycin and omeprazole resulted in significantly
      fewer uses of ulcer-related health care resources than conventional antisecretory
      therapy during a 1-year follow-up and significant savings in associated costs
      during the same period. Patients who received clarithromycin plus omeprazole also
      showed a significantly improved clinical outcome compared with patients who
      received only omeprazole or ranitidine.

PMID- 9570171
TI  - Homocysteine and ischemic heart disease: results of a prospective study with
      implications regarding prevention.
AB  - BACKGROUND: Results from prospective studies of serum homocysteine levels and
      ischemic heart disease (IHD) are inconclusive. We carried out a further
      prospective study to help clarify the position. METHODS: In the British United
      Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years,
      we measured homocysteine levels in stored serum samples and analyzed data from
      229 men without a history of IHD at study entry who subsequently died of IHD and
      1126 age-matched control subjects (nested case-control design). RESULTS: Serum
      homocysteine levels were significantly higher in men who died of IHD than in men
      who did not (mean, 13.1 vs 11.8 micromol/L; P<.001). The risk of IHD among men in
      the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times
      after adjusting for other risk factors) the risk among men in the lowest quartile
      (95% confidence interval [CI], 1.8-4.7). There was a continuous dose-response
      relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L
      increase in the serum homocysteine level. After adjustment for apolipoprotein B
      levels and blood pressure, this estimate was 33% (95% CI, 22%-59%). In a meta
      analysis of the retrospective studies of homocysteine level and myocardial
      infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%)
      increase in risk for a 5-micromol/L increase in the homocysteine level, possibly
      because the participants were younger; the relationship between serum
      homocysteine level and IHD seems to be stronger in younger persons than in older
      persons. CONCLUSIONS: Our positive results help resolve the uncertainty that
      resulted from previous prospective studies. The epidemiological, genetic, and
      animal evidence together indicate that the association between serum homocysteine
      level and IHD is likely to be causal. A general increase in consumption of the
      vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be
      expected to reduce mortality from IHD.

PMID- 9570172
TI  - Bacteremic pneumonia in neutropenic patients with cancer: causes, empirical
      antibiotic therapy, and outcome.
AB  - BACKGROUND: Bacteremic pneumonia is a major cause of death among neutropenic
      patients with cancer. METHODS: We analyzed the causes, empirical antibiotic
      therapy, and outcome of 40 consecutive cases of bacteremic pneumonia identified
      among 408 episodes of bacteremia in adult neutropenic patients with cancer,
      prospectively documented from 1986 to 1995. RESULTS: The most frequent causative
      organisms were Pseudomonas aeruginosa (17 cases), Streptococcus pneumoniae (12
      cases), Escherichia coli (5 cases), and Streptococcus mitis (3 cases). Overall,
      P. aeruginosa and S. pneumoniae caused 72.5% of all episodes of bacteremic
      pneumonia, compared with 11.4% of bacteremic episodes from other sources (P<
      .001). Thirty patients received ceftazidime and 10 patients received imipenem as
      the beta-lactam component of the initial empirical treatment. All strains of P.
      aeruginosa were susceptible to both agents. Forty-seven percent of streptococcal
      strains were penicillin resistant and showed a decreased susceptibility to
      ceftazidime (minimum inhibitory concentration ranged from 1 to 64 microg/mL).
      Five patients (12.5%) were considered to have received inappropriate empirical
      antibiotic therapy. Attributable mortality in patients with bacteremic pneumonia
      was higher than in patients with bacteremia from other sources; 22 (55%) of the
      40 patients with bacteremic pneumonia died, whereas 39 (10.6%) of the 368
      patients with bacteremia from other sources died (P<.001). CONCLUSIONS: Our data
      suggest that bacteremic pneumonia in neutropenic cancer patients is associated
      with a poor outcome and that empirical antibiotic therapy for neutropenic
      patients with pneumonia should include agents active against both P. aeruginosa
      and cephalosporin-resistant streptococci.

PMID- 9570173
TI  - The incidence of symptomatic venous thromboembolism during and after prophylaxis
      with enoxaparin: a multi-institutional cohort study of patients who underwent hip
      or knee arthroplasty. Canadian Collaborative Group.
AB  - BACKGROUND: Despite low molecular weight heparin prophylaxis, the incidence of
      venographically detected, residual deep vein thrombosis after hip and knee
      arthroplasty remains high, at approximately 15% and 30%, respectively. Most of
      these thrombi are asymptomatic and of unknown clinical significance.
      Nevertheless, because they have the potential to grow, limiting prophylaxis to
      the in-hospital period may provide inadequate protection. METHODS: We studied a
      cohort of 1984 consecutive patients who had hip or knee arthroplasty at 1 of 28
      participating hospitals. Patients received enoxaparin prophylaxis, 30 mg
      subcutaneously every 12 hours for up to 14 days, and underwent predischarge
      compression ultrasonography. Study end points were symptomatic deep vein
      thrombosis or pulmonary embolism during and after prophylaxis, asymptomatic
      venous thrombosis detected by predischarge compression ultrasonography, and major
      hemorrhage. The duration of follow-up was 84 days. RESULTS: Enoxaparin treatment
      was started a mean (+/- SD) of 17.9 +/- 10.4 hours after the completion of
      surgery and was given for a mean of 18.0 +/- 6.9 doses. Eighty-two patients
      (4.1%; 95% confidence interval, 3.3%-5.0%) developed venous thromboembolism. The
      rates of thromboembolic events during and after prophylaxis were 2.1% and 2.0%,
      respectively. Only 3 patients (0.15%) had abnormal predischarge compression
      ultrasonography. Three patients (0.15%) died of pulmonary embolism. Major
      hemorrhage occurred in 58 patients (2.9%; 95% confidence interval, 2.2%-3.7%).
      CONCLUSIONS: Postoperative prophylaxis with enoxaparin for a mean of 9 days is
      associated with a clinically acceptable rate of symptomatic venous
      thromboembolism and major hemorrhage. Predischarge compression ultrasonography
      cannot be justified.

PMID- 9570174
TI  - Reconceptualizing advance care planning from the patient's perspective.
AB  - BACKGROUND: Traditional academic assumptions about advance care planning (ACP)
      include the following: (1) the purpose of ACP is preparing for incapacity; (2)
      ACP is based on the ethical principle of autonomy and the exercise of control;
      (3) the focus of ACP is completing written advance directive forms; and (4) ACP
      occurs within the context of the physician-patient relationship. These
      assumptions about ACP have never been empirically validated. OBJECTIVE: To
      examine the traditional academic assumptions by exploring ACP from the
      perspective of patients actively participating in the planning process. METHODS:
      Forty-eight patients (30 men and 18 women with a mean age of 48.3 years) who were
      undergoing hemodialysis were interviewed 6 months after receiving an advance
      directive form. Their experience of ACP was noted in interviews that were
      audiotaped, transcribed, and analyzed. RESULTS: The participants said that their
      purpose in ACP was to prepare for death and dying, and their underlying goals
      included the exercise of control and an attempt to relieve burdens placed on
      loved ones. Advance care planning was viewed as a social process, and completing
      a written advance directive form was often regarded as unnecessary. Participants
      often involved close loved ones, but physicians infrequently. CONCLUSIONS: The
      traditional academic assumptions are not fully supported from the perspective of
      patients involved in ACP. The patients we interviewed stated that (1) the purpose
      of ACP is not only preparing for incapacity but also preparing for death; (2) ACP
      is not based solely on autonomy and the exercise of control, but also on personal
      relationships and relieving burdens placed on others; (3) the focus of ACP is not
      only on completing written advance directive forms but also on the social
      process; and (4) ACP does not occur solely within the context of the physician
      patient relationship but also within relationships with close loved ones.

PMID- 9570175
TI  - Clinical and nonclinical predictors of the cost of coronary bypass surgery:
      potential effects on health care delivery and reimbursement.
AB  - BACKGROUND: Health care providers are being pressured to lower the cost of care.
      Because of the inherent cost variability in providing health care, as
      reimbursement falls, providers may not be able to cover all costs. Understanding
      the underlying causes of this wide variability is important in determining
      optimum pricing. Prior studies on the cost of coronary bypass surgery have
      determined which clinical variables affect cost, yet none have studied
      nonclinical variables that can influence the cost of coronary bypass surgery.
      METHODS: In a cohort of 882 consecutive patients with treatment classified in the
      diagnosis-related group (DRG) 107, we examined 55 clinical and nonclinical
      variables obtained from our prospective database. For explanatory purposes, we
      used multiple linear regression to determine the variables that were predictive
      of direct cost and the magnitude of contribution of each variable. RESULTS:
      Eleven clinical and 4 nonclinical variables were predictive of direct cost.
      Nonclinical variables added significant cost-predictive information beyond that
      of the traditional clinical variables, and their magnitude of effect was equal to
      or greater than the traditional clinical variables. CONCLUSIONS: Nonclinical
      patient characteristics add important predictive information concerning the cost
      of coronary bypass surgery to traditional clinical variables. These data will be
      important in developing contracting strategies, in the evaluation of individual
      physician performance, and in modifying national methods of reimbursement.

PMID- 9570176
TI  - Methicillin-resistant Staphylococcus aureus in a high school wrestling team and
      the surrounding community.
AB  - OBJECTIVES: To describe a community outbreak of methicillin-resistant
      Staphylococcus aureus (MRSA) and to investigate risk factors for MRSA
      transmission and infection in a wrestling team. DESIGN: Case series and
      retrospective cohort study. SETTING: A high school wrestling team and the
      surrounding community in southern Vermont, 1993 to 1994. PATIENTS OR OTHER
      PARTICIPANTS: The case series included persons whose MRSA-positive infections
      were identified at a hospital laboratory from January 1, 1993, through February
      28, 1994, and a health maintenance organization laboratory from July 1, 1993,
      through February 28, 1994. A wrestling team case-patient was a 1993-1994 team
      member with an MRSA-positive culture during the period from January 1, 1993,
      through February 28, 1994. INTERVENTIONS: Visual inspection of wrestlers before
      matches was instituted. Affected wrestlers were excluded from wrestling and
      advised to seek appropriate medical care. Heightened attention was given to
      personal and environmental hygiene. MAIN OUTCOME MEASURES: Colonization or
      infection with MRSA. RESULTS: Seven of 32 team members were MRSA positive (6
      infected, 1 colonized). All lesion-positive wrestlers were tested by pulsed field
      gel electrophoresis and found to be infected with the same MRSA strain, as were 6
      nonwrestlers. No risk factors for MRSA infection were identified. CONCLUSIONS:
      The MRSA was transmitted among members of a wrestling team. Infection with MRSA
      should be suspected in outbreaks of boils that are nonresponsive to standard
      antibiotic therapy among healthy participants of contact sports and their close
      contacts.

PMID- 9570177
TI  - Changes in plasma lipids and lipoproteins in humans during a 2-year period of
      dietary restriction in Biosphere 2.
AB  - BACKGROUND: A cohort study was performed of 8 people sealed inside Biosphere 2 to
      evaluate the effects of dietary restriction in humans on lipid and lipoprotein
      levels and the relationship of these levels to energy, fat, and protein content
      of the diet, and body weight, weight change, and energy expenditure. METHODS:
      Eight healthy people aged 27 to 67 years, 4 women and 4 men, were sealed inside
      Biosphere 2 from September 26, 1991, to September 26, 1993, the longest sustained
      period in an "isolated confined environment" on record. They were studied
      throughout confinement and for more than 2 years after their exit and return to
      an ad libitum diet. Food available was severely restricted during most of the 2
      year period inside Biosphere 2. High work output was maintained and food quality
      remained high, resulting in prolonged restriction of energy intake without
      malnutrition. RESULTS: Fasting plasma cholesterol, triglyceride, and high-density
      lipoprotein (HDL) cholesterol levels; HDL subfraction distribution; dietary
      energy, fat, and protein content intake; and height, weight, weight change, and
      energy expenditure were measured. Total plasma cholesterol and triglyceride
      levels decreased 30% and 45%, respectively. The HDL and low-density lipoprotein
      levels also decreased and, in some participants, levels of HDL2 subfractions were
      increased. Multivariate analysis showed that the major cause of these changes was
      energy restriction. CONCLUSIONS: Energy restriction was the major factor leading
      to low lipid and lipoprotein levels. Energy restriction with adequate nutrition
      of young and middle-aged people may substantially reduce risk for atherosclerosis
      and consequent coronary artery and cerebrovascular disease.

PMID- 9570178
TI  - A preliminary placebo-controlled crossover trial of fludrocortisone for chronic
      fatigue syndrome.
AB  - OBJECTIVE: To provide a preliminary assessment of the efficacy and safety of
      fludrocortisone acetate treatment of chronic fatigue syndrome. DESIGN: A placebo
      controlled, double-blind, random-allocation crossover trial of 6 weeks of
      fludrocortisone. SETTING: An outpatient clinical trials unit. PATIENTS: Twenty
      five participants with chronic fatigue syndrome (mean age, 40 years; 19 [76%]
      women; mean duration of illness, 7.0 years) were recruited from a research and
      clinic registry. Five patients withdrew from the trial. INTERVENTIONS: All
      participants were scheduled to receive fludrocortisone acetate (0.1-0.2 mg) or a
      placebo for 6 weeks in each treatment. MAIN OUTCOME MEASURES: Self-administered
      questionnaires were completed at the beginning and end of each treatment arm that
      asked patients to rate the severity of their symptoms on a visual analogue scale.
      The Medical Outcomes Study 36-Item Short-Form Health Survey, a reaction time
      test, and a treadmill exercise test were used to assess functional status. Blood
      pressure, heart rate, and plasma norepinephrine levels were obtained at baseline.
      Blood pressure and heart rate were recorded at the end of the exercise test and
      monitored at all subsequent visits. RESULTS: At baseline, the study participants
      reported symptom severity greater than 5 for most symptoms, and all had evidence
      of marked functional impairments. No improvement was observed in the severity of
      any symptom or in any test of function for the 20 participants who completed both
      arms of the trial. Blood pressure and heart rate readings were unaffected by
      treatment, and plasma norepinephrine levels did not differ from those of a
      healthy control group. The incidence of adverse experiences was similar in the
      fludrocortisone and placebo arms of the trial. CONCLUSION: Low-dose
      fludrocortisone does not provide sufficient benefit to be evident in a
      preliminary blinded trial of unselected patients with chronic fatigue syndrome.

PMID- 9570179
TI  - Hyperkalemia in hospitalized patients: causes, adequacy of treatment, and results
      of an attempt to improve physician compliance with published therapy guidelines.
AB  - BACKGROUND: Hyperkalemia is a common, potentially life-threatening disorder.
      Electrocardiograms are considered to be sensitive indicators of the presence of
      hyperkalemia. Since the treatment of hyperkalemia involves relatively few
      maneuvers and because its success can be objectively scored, we investigated how
      physicians manage this disorder and how successful their prescribed therapy is.
      We also sought to determine whether treatment could be improved by providing the
      treating physicians with therapy guidelines on a real-time basis. METHODS:
      Consecutive patients with hyperkalemia were identified by review of laboratory
      records. During the observation-only phase of the study, demographic data,
      contributing causes, electrocardiogram findings, treatments used, compliance with
      prescribing guidelines, and patient outcome were recorded. During the subsequent
      notification phase of the study, treatment recommendations were sent to the
      patient's ward when the elevated potassium value was noted. The same outcome data
      were collected. RESULTS: There were 127 episodes of hyperkalemia during the
      observation-only phase and 115 during the notification phase. No patients died or
      had life-threatening cardiac arrhythmias. Electrocardiographic abnormalities
      consistent with hyperkalemia were observed in only 14% of episodes. Renal failure
      (77%), drugs (63%), and hyperglycemia (49%) contributed to most episodes.
      Treatments used were exchange resin (51%), insulin (46%), calcium (36%),
      bicarbonate (34%), and albuterol (4%). The agents were equally efficacious. The
      time to first treatment was shorter in patients with potassium levels of 6.5
      mmol/L or more than in patients with lower values (2.1 +/- 2.2 vs 2.8 +/- 2.4
      hours; P<.05). Treatment was better in the intensive care unit than on regular
      wards. Only 39% of episodes during the observation-only period met the
      predetermined criteria for monitoring and diagnosis, initial treatment, and
      follow-up. During the notification period, physician performance was no better;
      only 42% of episodes met all criteria. The laboratory transmitted a copy of the
      guidelines to the patient's ward only 38% of the time. In a separate analysis of
      these episodes, there was no improvement in treatment. Physicians who did not
      receive the notification fulfilled all treatment criteria more often than
      physicians who did (50% vs 30%; P<.05). CONCLUSIONS: Although treatment of
      hyperkalemia was frequently suboptimal, no serious arrhythmias and no deaths
      complicated management of 242 episodes of severe hyperkalemia. A narrowly
      targeted effort to improve physician management of a disorder with discrete
      treatment options did not improve therapy.

PMID- 9570180
TI  - Survival after massive (>2000) Africanized honeybee stings.
AB  - We report the clinical case of a man who survived a massive attack of Africanized
      bees (>2000 bee stings). The man experienced anaphylactic shock and multisystem
      organ failure (neurologic, hepatic, renal, and hematologic failure). He was
      treated with administration of dopamine hydrochloride, antihistaminic agents,
      corticosteroids, fluid and electrolyte replenishment, peritoneal dialysis, and
      plasmapheresis. No sequelae have been observed during follow-up.

PMID- 9570181
TI  - Colon cancer screening: performance and payments.

PMID- 9570182
TI  - Endoscopists need to clean up their act--literally.

PMID- 9570183
TI  - Doxycycline: new ways to use an old antibiotic.

PMID- 9570184
TI  - Paroxysmal tachycardia in a patient without panic disorder.

PMID- 9570185
TI  - Remission of relapsing Pseudomonas aeruginosa bronchopulmonary infection
      following antiretroviral therapy.

PMID- 9570186
TI  - Capitation rates and proprietary secrets.

PMID- 9570187
TI  - Meeting highlights: highlights of the 70th Scientific Sessions of the American
      Heart Association.

PMID- 9570188
TI  - New targeted AHA research program: Cardiovascular Care and Outcomes.

PMID- 9570189
TI  - Estrogens, progestins, and heart disease: can endothelial function divine the
      benefit?

PMID- 9570190
TI  - Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors.
AB  - BACKGROUND: The antiarrhythmic drugs quinidine and verapamil are known to block
      alpha1-adrenoceptors (alpha1ARs). Alpha1ARs are a heterogeneous family of three
      subtypes (alpha1A, alpha1B, and alpha1D), and little is known about the effects
      of quinidine and verapamil on the different human alpha1AR subtypes. METHODS AND
      RESULTS: Reverse transcriptase-polymerase chain reaction showed that all alpha1AR
      subtypes are expressed in both human heart (atrium and ventricle) and the
      mesenteric artery. Pharmacological profiles of quinidine and verapamil actions on
      the alpha1AR subtypes were characterized with Chinese hamster ovary cells stably
      expressing cloned human alpha1AR subtypes. Radioligand binding studies showed
      that quinidine and verapamil had high affinities for all alpha1AR subtypes. Also,
      both drugs synergistically inhibited alpha1AR-mediated inositol 1,4,5
      triphosphate production at the clinical effective concentration range (1
      micromol/L quinidine and 0.1 micromol/L verapamil). CONCLUSIONS: The results show
      that all alpha1AR subtypes are expressed in the human cardiovascular system and
      that quinidine and verapamil may have a potent, synergistic inhibitory effect on
      the alpha1ARs. Clinically observed hypotension after quinidine plus verapamil can
      be explained by their synergistic inhibitory effects on human alpha1ARs.

PMID- 9570191
TI  - Recent national patterns of warfarin use in atrial fibrillation.
AB  - BACKGROUND: Studies of selected populations suggest that anticoagulation in
      atrial fibrillation is underused and that nonclinical factors influence the use
      of this stroke-preventing therapy. We wished to examine recent national trends
      and predictors of warfarin sodium use in atrial fibrillation. METHODS AND
      RESULTS: A nationally representative sample of office visits from the 1989 to
      1996 National Ambulatory Medical Care Surveys was used. We selected 1125 visits
      by patients with atrial fibrillation, including 877 visits to cardiologists and
      primary care physicians in which apparent contraindications for anticoagulation
      were absent. The principal outcome measure was the proportion of visits with
      warfarin reported. We analyzed trends in warfarin use and statistically evaluated
      the predictors of warfarin use. Warfarin use increased from 13% of atrial
      fibrillation visits in 1989 to 40% in 1993 (P for trend <.001) in patients
      without contraindications. Between 1993 and 1996, however, there was no change in
      warfarin use. Independent of other factors, warfarin was significantly more
      likely to be reported in patients with a history of stroke and in patients
      residing outside of the South. CONCLUSIONS: Warfarin use in atrial fibrillation
      has not increased recently, indicating inadequate implementation of this highly
      effective therapy. Barriers to anticoagulation in real-world clinical practice
      need to be identified and addressed.

PMID- 9570192
TI  - Combined hormone replacement therapy does not protect women against the age
      related decline in endothelium-dependent vasomotor function.
AB  - BACKGROUND: Improvement in endothelial function may be an important mechanism by
      which estrogen replacement therapy protects postmenopausal women against coronary
      artery disease. However, combined hormone replacement therapy is more frequently
      used owing to the risk of uterine cancer with estrogen-only therapy. Concurrent
      progesterone treatment may attenuate the beneficial effects of estrogens not only
      on the lipid profile but also on the endothelium. METHODS AND RESULTS: We studied
      endothelial vasomotor function in 100 healthy postmenopausal women aged 53.3+/
      2.9 years randomized to either combined hormone replacement therapy (n=46) or no
      substitution (n=54) 2.9+/-0.5 years earlier. In addition, 30 healthy
      premenopausal women aged 30.3+/-4.2 years were studied. With external ultrasound,
      brachial artery diameter was measured at rest, during reactive hyperemia (with
      increased flow causing endothelium-dependent dilation), and after sublingual
      nitroglycerin (causing endothelium-independent dilation). Compared with
      premenopausal women, flow-mediated dilation was significantly reduced in both
      postmenopausal groups. In the postmenopausal women, total cholesterol was lower
      in the treated women (5.66+/-0.83 versus 6.13+/-0.92 mmol/L; P=.025), whereas HDL
      cholesterol was similar (1.91+/-0.53 versus 1.85+/-0.46 mmol/L; P=NS). Dilation
      to flow and to nitroglycerin was similar in the two postmenopausal groups (flow:
      2.5+/-2.9% versus 2.2+/-2.2%, P=NS; nitrate: 18.7+/-5.9% versus 17.2+/-6.2%,
      P=NS). CONCLUSIONS: Long-term combined oral hormone replacement therapy is
      without beneficial effects on endothelial vasomotor function in healthy
      postmenopausal women. This supports the view that progesterone may attenuate the
      beneficial effects of unopposed estrogen replacement.

PMID- 9570193
TI  - Predictors of stroke complicating carotid artery stenting.
AB  - BACKGROUND: The evolving technique of carotid stenting is being evaluated as an
      alternative to endarterectomy. Identification of the factors that predispose a
      patient to neurological complications would facilitate further refinement of the
      technique and optimize patient selection. METHODS AND RESULTS: We analyzed the
      impact of various clinical, morphological, and procedural determinants on the
      development of procedural strokes in 231 patients who underwent elective
      (primary) stenting of 271 extracranial carotid arteries. The mean age of the
      patients was 68.7+/-10 years, 165 (71%) were males, and 139 (60%) had symptoms
      attributed to the lesion treated. This series represented a high-risk subset with
      164 patients (71%) having significant coronary artery disease, 91 (39%) having
      bilateral disease, and 28 (12%) having contralateral carotid occlusion. Of the
      treated vessels, 59 (22%) had prior carotid endarterectomy, 66 (24%) had
      ulcerated plaques, and 87 (32%) had calcified lesions. Only 37 treated vessels
      (14%) would have been eligible for inclusion in the North American Symptomatic
      Carotid Endarterectomy Trial (NASCET). There were 17 (6.2%) minor and 2 (0.7%)
      major strokes during and within 30 days of the procedure. NASCET-eligible
      patients had a low (2.7%) risk of procedural strokes after carotid stenting. The
      results of multivariate analysis revealed advanced age (P=.006) and presence of
      long or multiple stenoses (P=.006) as independent predictors of procedural
      strokes. CONCLUSIONS: During this procedural developmental phase of carotid
      stenting, neurological complications were highly dependent on patient selection.
      Advanced age and long or multiple stenoses were independent predictors of
      procedural stroke.

PMID- 9570194
TI  - Left ventricular structure and function in children infected with human
      immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric
      Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2
      HIV) Study Group.
AB  - BACKGROUND: The frequency of, course of, and factors associated with
      cardiovascular abnormalities in pediatric HIV are incompletely understood.
      METHODS AND RESULTS: A baseline echocardiogram (median age, 2.1 years) and 2
      years of follow-up every 4 months were obtained as part of a prospective study on
      196 vertically HIV-infected children. Age- or body surface area-adjusted z scores
      were calculated by use of data from normal control subjects. Although 88% had
      symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative
      incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were
      abnormal at baseline (decreased left ventricular fractional shortening [LV FS]
      and contractility and increased heart rate and LV dimension, mass, and wall
      stresses). Most of the abnormal baseline cardiac measurements correlated with
      depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart
      rate and LV mass showed significantly progressive abnormalities, whereas FS and
      contractility tended to decline. No association was seen between longitudinal
      changes in FS and CD4 cell count z score. Children who developed encephalopathy
      during follow-up had depressed initial FS, and FS continued to decline during
      follow-up. CONCLUSIONS: Subclinical cardiac abnormalities in HIV-infected
      children are common, persistent, and often progressive. Dilated cardiomyopathy
      (depressed contractility and dilatation) and inappropriate LV hypertrophy
      (elevated LV mass in the setting of decreased height and weight) were noted.
      Depressed LV function correlated with immune dysfunction at baseline but not
      longitudinally, suggesting that the CD4 cell count may not be a useful surrogate
      marker of HIV-associated LV dysfunction. However, the development of
      encephalopathy may signal a decline in FS.

PMID- 9570195
TI  - Assessment of the contribution that direct allorecognition makes to the
      progression of chronic cardiac transplant rejection in humans.
AB  - BACKGROUND: Two populations of T cells contribute to allograft rejection. T cells
      with direct allospecificity are activated after recognition of intact MHC
      alloantigens displayed at the surface of donor passenger leukocytes carried
      within the graft. In contrast, T cells with indirect allospecificity recognize
      donor alloantigens as processed peptides associated with self (recipient)-MHC
      class II molecules. In small animal models of transplantation, direct pathway T
      cells dominate the acute rejection process and are rendered tolerant to the graft
      after the loss of donor passenger leukocytes. It has been argued that indirect
      pathway T cells contribute substantially to continual graft damage after
      passenger cell loss. The purpose of this study was to determine whether donor
      specific tolerance could be detected in T cells with direct anti-donor
      allospecificity in human heart transplant recipients after prolonged graft
      residence. METHODS AND RESULTS: Alloreactive helper (HTLf) and cytotoxic (CTLf) T
      cells were enumerated by use of limiting dilution analysis. These assay systems
      were refined to make them specific for the direct pathway of allorecognition and
      more sensitive in the case of the HTLf assay. Recipient:anti-donor frequencies
      were generated in 10 long-term recipients of heart grafts with progressive
      chronic rejection and compared with those against equivalently HLA mismatched
      recipient:third-party controls. For HTLf, direct pathway donor-specific
      hyporesponsiveness was detected in 5 of the 10 recipients (HTLf<1:100,000). Of
      these 5 recipients, 4 also had low anti-donor CTLf (<1:100,000). In the 5th
      recipient, although the CTLf was >1:100,000, it was significantly lower than that
      estimated against the third-party control. CONCLUSIONS: Donor-specific
      hyporesponsiveness is demonstrated in 50% of recipients in both the HTLf and CTLf
      compartments of the direct alloresponse. Direct allorecognition therefore appears
      unlikely to be responsible for the progression of chronic rejection, implicating
      indirect allorecognition as the predominant immunological driving force.
      Furthermore, these data have potential implications for graft outcome, adjustment
      of immunosuppression, and recipient monitoring.

PMID- 9570196
TI  - New mutations in the KVLQT1 potassium channel that cause long-QT syndrome.
AB  - BACKGROUND: Long-QT syndrome (LQTS) is an inherited cardiac arrhythmia that
      causes sudden death in young, otherwise healthy people. Four genes for LQTS have
      been mapped to chromosome 11p15.5 (LQT1), 7q35-36 (LQT2), 3p21-24 (LQT3), and
      4q25-27 (LQT4). Genes responsible for LQT1, LQT2, and LQT3 have been identified
      as cardiac potassium channel genes (KVLQT1, HERG) and the cardiac sodium channel
      gene (SCN5A). METHODS AND RESULTS: After studying 115 families with LQTS, we used
      single-strand conformation polymorphism (SSCP) and DNA sequence analysis to
      identify mutations in the cardiac potassium channel gene, KVLQT1. Affected
      members of seven LQTS families were found to have new, previously unidentified
      mutations, including two identical missense mutations, four identical splicing
      mutations, and one 3-bp deletion. An identical splicing mutation was identified
      in affected members of four unrelated families (one Italian, one Irish, and two
      American), leading to an alternatively spliced form of KVLQT1. The 3-bp deletion
      arose de novo and occurs at an exon-intron boundary. This results in a single
      base deletion in the KVLQT1 cDNA sequence and alters splicing, leading to the
      truncation of KVLQT1 protein. CONCLUSIONS: We have identified LQTS-causing
      mutations of KVLQT1 in seven families. Five KVLQT1 mutations cause the truncation
      of KVLQT1 protein. These data further confirm that KVLQT1 mutations cause LQTS.
      The location and character of these mutations expand the types of mutation,
      confirm a mutational hot spot, and suggest that they act through a loss-of
      function mechanism or a dominant-negative mechanism.

PMID- 9570197
TI  - Effects of the intracoronary infusion of cocaine on left ventricular systolic and
      diastolic function in humans.
AB  - BACKGROUND: In dogs, a large amount of intravenous cocaine causes a profound
      deterioration of left ventricular (LV) systolic function and an increase in LV
      end-diastolic pressure. This study was done to assess the influence of a high
      intracoronary cocaine concentration on LV systolic and diastolic function in
      humans. METHODS AND RESULTS: In 20 patients (14 men and 6 women aged 39 to 72
      years) referred for cardiac catheterization for the evaluation of chest pain, we
      measured heart rate, systemic arterial pressure, LV pressure and its first
      derivative (dP/dt), and LV volumes and ejection fraction before and during the
      final 2 to 3 minutes of a 15-minute intracoronary infusion of saline (n=10,
      control subjects) or cocaine hydrochloride 1 mg/min (n=10). No variable changed
      with saline. With cocaine, the drug concentration in blood obtained from the
      coronary sinus was 3.0+/-0.4 (mean+/-SD) mg/L, similar in magnitude to the blood
      cocaine concentration reported in abusers dying of cocaine intoxication. Cocaine
      induced no significant change in heart rate, LV dP/dt (positive or negative), or
      LV end-diastolic volume, but it caused an increase in systolic and mean arterial
      pressures, LV end-diastolic pressure, and LV end-systolic volume, as well as a
      decrease in LV ejection fraction. CONCLUSIONS: In humans, the intracoronary
      infusion of cocaine sufficient in amount to achieve a high drug concentration in
      coronary sinus blood causes a deterioration of LV systolic and diastolic
      performance.

PMID- 9570199
TI  - Ischemic preconditioning in the intact rat heart is mediated by delta1- but not
      mu- or kappa-opioid receptors.
AB  - BACKGROUND: Our laboratory has previously shown that delta-opioid receptors are
      involved in the cardioprotective effect of ischemic preconditioning in the rat
      heart. However, this class of receptors consists of two subtypes, delta1, and
      delta2, and mu- or kappa-opioid receptors may also exist in the heart. Therefore,
      the purpose of the present study was to test the hypothesis that ischemic
      preconditioning is mediated through stimulation of one or both delta-opioid
      receptor subtypes. METHODS AND RESULTS: Anesthetized, open chest, male Wistar
      rats were assigned to 1 of 14 groups. All animals were subjected to 30 minutes of
      occlusion and 2 hours of reperfusion. Ischemic preconditioning was elicited by
      three 5-minute occlusion periods interspersed with 5 minutes of reperfusion. Two
      doses of 7-benzylidenenaltrexone (BNTX; 1 and 3 mg/kg i.v.), a selective delta1
      opioid receptor antagonist, or naltriben (NTB; 1 and 3 mg/kg i.v.), a selective
      delta2-opioid receptor antagonist, were given before ischemic preconditioning. To
      test for a role of mu-opioid receptors, rats were pretreated with beta
      funaltrexamine (beta-FNA; 15 mg/kg s.c), an irreversible mu-opioid receptor
      antagonist, 24 hours before ischemic preconditioning or given the mu-opioid
      receptor agonist D-Ala,2N-Me-Phe,4glycerol5-enkephalin (DAMGO) as three 5-minute
      infusions (1, 10, and 100 microg/kg per infusion i.v., respectively) interspersed
      with 5-minute drug-free periods before the prolonged ischemic and reperfusion
      periods (lowDAMGO, medDAMGO, and hiDAMGO, respectively). The involvement of kappa
      opioid receptors was tested by administering one of two doses of nor
      binaltorphimine (nor-BNI; 1 and 5 mg/kg i.v.) before ischemic preconditioning.
      Infarct size (IS) as a percent of the area at risk (AAR) was measured by
      triphenyltetrazolium stain. Ischemic preconditioning markedly reduced IS/AAR
      (14+/-4%, P<.05) compared with control (55+/-4%). NTB, beta-FNA, and nor-BNI were
      unable to block the cardioprotective effect of ischemic preconditioning. In
      addition, DAMGO had no effect on IS/AAR. However, the high dose of BNTX (3 mg/kg
      i.v.) significantly attenuated the cardioprotective effect of ischemic
      preconditioning (39+/-5%; P<.05 versus control and ischemic preconditioning).
      CONCLUSIONS: These results indicate that delta1-opioid receptors play an
      important role in the cardioprotective effect of ischemic preconditioning in the
      rat heart.

PMID- 9570198
TI  - Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth
      muscle cell proliferation and neointima formation after balloon injury in rats.
AB  - BACKGROUND: Loss of endothelial NO production after arterial injury may
      contribute to restenosis, characterized by neointima formation and elastic
      recoil. Adenovirus-mediated transfer of the gene encoding NO synthase (NOS) in
      balloon-injured arteries may restore NO production and inhibit neointima
      formation. METHODS AND RESULTS: After balloon injury, rat carotid arteries were
      transduced with 3x10(10) pfu/mL recombinant adenovirus carrying the human
      endothelial constitutive NOS cDNA (AdCMVceNOS, n=8) or no cDNA (AdRR5, n=8).
      ceNOS expression was confirmed by immunoblot analysis of vascular extracts and
      was localized by immunostaining in 30% of medial smooth muscle cells (SMCs) and
      in the adventitia of AdCMVceNOS-transduced arteries. Vascular cGMP levels were
      reduced from 3.9 pmol/g wet wt in uninjured arteries to 0.7 pmol cGMP/g after
      AdRR5 but were restored after ceNOS gene transfer (3.8 pmol cGMP/g wet wt, P<.05
      versus AdRR5). Intima-to-media ratio 2 weeks after injury was significantly
      reduced (0.19+/-0.02 in AdCMVceNOS-infected versus 0.69+/-0.07 in AdRR5-infected
      arteries, P<.05). In vitro, BrdU incorporation of AdCMVceNOS-infected SMCs was
      reduced by 28% compared with AdRR5-infected SMCs. Transduced cells from injured
      carotid arteries subjected to FACS sorting showed a significantly lower BrdU
      labeling index in ceNOS-infected rats (29+/-6% versus 43+/-5% and 45+/-4% in
      control, injured, and AdRR5-infected rats, respectively, P<.05). CONCLUSIONS:
      AdCMVceNOS gene transfer to balloon-injured rat carotid arteries restores
      vascular NO production and reduces neointima formation, at least in part because
      of an antiproliferative effect on medial SMCs. Adenovirus-mediated ceNOS gene
      transfer might reduce arterial restenosis after balloon angioplasty.

PMID- 9570201
TI  - A call for provisional stenting: the balloon is back!

PMID- 9570200
TI  - N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, markedly
      reduced infarct size in rabbit hearts.
AB  - BACKGROUND: N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor,
      reduces the glycogenolytic rate by inhibiting the alpha-1,6-glucosidase of
      glycogen-debranching enzyme in the liver, in addition to possessing an
      antihyperglycemic action by blocking alpha-1,4-glucosidase in the intestine.
      Because the reduction of the glycogenolytic rate may be one of the mechanisms of
      myocardial protection in ischemic preconditioning, the compounds inhibiting
      myocardial alpha-1,6-glucosidase may be protective against ischemic damage. Thus,
      we investigated whether MOR-14 could inhibit alpha-1,6-glucosidase and reduce the
      infarct size in rabbit hearts without collateral circulation. METHODS AND
      RESULTS: MOR-14 dose-dependently decreased the alpha-1,6-glucosidase activity in
      rabbit heart extract. A tracer study demonstrated the myocardial uptake of a
      considerable amount of MOR-14 sufficient to fully inhibit alpha-1,6-glucosidase.
      To assess the infarct size-reducing effect of MOR-14, 54 rabbits were subjected
      to 30-minute coronary occlusion followed by 48-hour reperfusion. Preischemic
      treatment with 25, 50, and 100 mg/kg of MOR-14 dose-dependently reduced the
      infarct size (to 26+/-4%, 19+/-3%, and 14+/-2% of the area at risk,
      respectively), compared with the saline control (45+/-5%) without altering the
      blood pressure or heart rate. Another 40 rabbits given 100 mg of MOR-14 or saline
      10 minutes before ischemia were euthanized at 10 or 30 minutes of ischemia for
      biochemical analysis. MOR-14 decreased the alpha-1,6-glucosidase activity to
      approximately 20% in vivo, reduced the glycogen breakdown, and attenuated the
      lactate accumulation at both 10 and 30 minutes of ischemia. CONCLUSIONS:
      Preischemic treatment with MOR-14 preserved glycogen, attenuated the accumulation
      of lactate, and reduced the myocardial infarct size by 69%. This cardioprotective
      effect was independent of changes of blood pressure and heart rate or regional
      blood flow. It may be associated with alpha-1,6-glucosidase inhibition, because
      MOR-14 markedly decreased the alpha-1,6-glucosidase activity in the heart.

PMID- 9570202
TI  - Images in cardiovascular medicine. Cardiac sarcoidosis.

PMID- 9570203
TI  - Images in cardiovascular medicine. Thrombosis of the superior sagittal sinus.

PMID- 9570204
TI  - American Heart Association report on the second public access defibrillation
      conference, April 17-19, 1997.

PMID- 9570205
TI  - Potential cost-effectiveness of public access defibrillation in the United
      States.
AB  - BACKGROUND: Approximately 360,000 Americans experience sudden cardiac arrest each
      year; current treatments are expensive and not very effective. Public access
      defibrillation (PAD) is a novel treatment for out-of-hospital sudden cardiac
      arrest that refers to use of automated external defibrillators by the lay public
      or by nonmedical personnel such as police. A clinical trial has been proposed to
      evaluate the effectiveness of public access defibrillation, but it is unclear
      whether such early defibrillation will offer sufficient value for money. Our
      objective was to estimate the potential cost-effectiveness of public access
      defibrillation by use of decision analysis. METHODS AND RESULTS: A decision model
      compared the potential cost-effectiveness of standard emergency medical services
      (EMS) systems with that of EMS supplemented by PAD. We considered defibrillation
      by lay responders or police, using an analysis with a US health-care perspective.
      Input data were derived from published data or fiscal databases. Future costs and
      effects were discounted at 3%. Monte Carlo simulation was performed to estimate
      the variability in the costs and effects of each program. Sensitivity analyses
      assessed the robustness of the results to changes in input data. A standard EMS
      system had a median cost of $5900 per cardiac arrest patient (interquartile
      range, IQR, $3200 to $10,900) and yielded a median of 0.25 quality-adjusted life
      years (IQR, 0.20 to 0.30). PAD by lay responders had a median incremental cost of
      $44,000 per additional quality-adjusted life year (IQR, $29,000 to $68,900). PAD
      by police had a median incremental cost of $27,200 per additional quality
      adjusted life year (IQR, $15,700 to $47,800). The results were sensitive to
      changes in the cost and relative survival benefit of PAD. CONCLUSIONS: Although
      more expensive than standard EMS for sudden cardiac arrest, PAD may be
      economically attractive. The effectiveness and cost-effectiveness of PAD should
      be assessed in a randomized, controlled trial.

PMID- 9570206
TI  - Automated external defibrillators: time for federal and state advocacy and
      broader utilization.

PMID- 9570208
TI  - Cytologic features of sarcomas in fluids.
AB  - BACKGROUND: Sarcomas account for < 6% of malignant effusions and their diagnosis
      usually is made in the setting of a known primary tumor. However, these tumors
      often exhibit a variety of features that can differ from those of the original
      neoplasm and may preclude the correct diagnosis. This article evaluates the
      cytomorphology of sarcomas in fluids and determines characteristic features for
      identification and classification. METHODS: The study included 24 Papanicolaou
      stained fluid samples (15 pleural, 8 peritoneal, and 1 pericardial) from patients
      with a diagnosis of sarcoma. The following features were evaluated: cellular
      arrangement, cellularity, nuclear/cytoplasmic ratio, background, quality and
      quantity of cytoplasm, cell borders, and nuclear details. RESULTS: All cytology
      specimens were diagnosed accurately as malignant. The histopathologic diagnoses
      were eight malignant fibrous histiocytomas, five leiomyosarcomas, three
      rhabdomyosarcomas, three liposarcomas, two high grade sarcomas, one osteogenic
      sarcoma, one synovial sarcoma, and one chondrosarcoma. Cytomorphologic features
      shared by sarcomas in metastatic sites included single cell arrangement (23 of
      24; 95.8%), indistinct cell borders (18 of 24; 75.0%), nuclear pleomorphism (18
      of 24; 75.0%) multinucleation (13 of 24; 54.2%), and proteinaceous background
      with lysed blood (17 of 24; 70.8%). CONCLUSIONS: Sarcomas in effusions share
      morphologic features that allow their correct diagnosis. Further
      subclassification can be attempted in the proper clinical setting and by
      comparison with the primary lesion.

PMID- 9570207
TI  - ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmia
      Devices: Executive Summary--a report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines
      (Committee on Pacemaker Implantation).

PMID- 9570209
TI  - Stereotactic fine-needle aspiration cytology of nonpalpable breast lesions:
      Institut Curie's experience of 243 histologically correlated cases.
AB  - BACKGROUND: The early diagnosis of nonpalpable breast lesions is a medical
      challenge because of the low specificity of different radiologic modalities. Fine
      needle aspiration cytology (FNAC) assisted by a stereotactic guidance is an
      adjunctive diagnostic approach in the management of these lesions. The primary
      purpose of this article was to assess the diagnostic accuracy of FNAC in patients
      with nonpalpable breast lesions. METHODS: Three hundred and seventy-one lesions
      from 357 patients (all female) underwent FNAC using the stereotactically guided
      technique. Of these cases, 243 lesions from 238 patients subsequently were
      acquired by surgical excisional biopsies and formed the basis of this study.
      Statistical analyses of the cytologic and the histologic diagnoses of these cases
      were performed. RESULTS: Histologically, 107 lesions (44%) were benign and 136
      lesions (56%) were malignant. Of the 136 malignant lesions, cytology was
      concordant in 73 lesions (53.7%), suspicious in 15 lesions (11.0%), false
      negative in 12 lesions (8.8%) (benign), and unsatisfactory in 36 lesions (26.5%).
      Among the 107 benign lesions, cytology was concordant with histology in 75
      lesions (70.1%), whereas 4 lesions (3.7%) and 28 lesions (26.2%) were
      cytologically suspicious and unsatisfactory, respectively. No false-positive
      cytologies were found in the current series. CONCLUSIONS: The current prospective
      study indicates that mammography combined with FNAC provides an accurate and
      practical diagnostic approach for the majority of nonpalpable lesions. Patients
      with unsatisfactory and false-negative lesions should undergo excisional biopsy.

PMID- 9570210
TI  - Aspiration cytology of malignant neoplasms associated with granulomas and
      granuloma-like features: diagnostic dilemmas.
AB  - BACKGROUND: Malignant lymphomas and solid tumors that mimic or are associated
      with epithelioid granulomas are widely recognized in surgical pathology, but have
      received little attention in the cytopathology literature. In this study the
      authors present their experience with six such cases in which the presence of
      granulomas or granuloma-like features posed a diagnostic difficulty on fine
      needle aspiration cytology (FNAC). METHODS: Clinical data, FNAC, and follow-up
      surgical specimens from six patients presenting with neck masses were reviewed.
      RESULTS: Only one case was diagnosed confidently as metastatic squamous cell
      carcinoma with an extensive granulomatous response; the other five were
      interpreted as "atypical" with descriptive cytology and a differential diagnoses
      including granulomatous inflammation, in addition to a caveat of "cannot exclude
      malignancy." Biopsy studies in these cases were recommended in view of the
      atypical cytologic findings and strong clinical suspicion of malignancy in each
      case. The histologic findings in two cases revealed Hodgkin's disease with
      exuberant granulomatous response. The remaining three cases were found to be
      malignant neoplasms with epithelioid morphologic features and included one
      example each of diffuse large cell lymphoma, anaplastic carcinoma of the thyroid,
      and lymphoepithelial carcinoma. CONCLUSIONS: Malignancies associated with
      granulomas and tumor cells mimicking epithelioid histiocytes may be difficult to
      diagnose accurately on FNAC. The cytologic differential diagnosis of a
      "granulomatous" process should include malignant neoplasms. Excisional biopsy
      studies may be required for definitive diagnosis.

PMID- 9570211
TI  - Cytodiagnosis of metastatic amelanotic melanomas by fine-needle aspiration
      biopsy: adjunctival value of immunocytochemistry and electron microscopy.
AB  - BACKGROUND: The cytologic diagnosis (CD) of metastatic amelanotic melanomas (MAM)
      is challenging because the tumor cells may mimic those of a carcinoma or a
      sarcoma in cytologic materials obtained by fine-needle aspiration biopsy (FNAB).
      METHODS: Thirty-five well documented cases of MAM at different anatomic sites
      with cytologic evaluation by FNAB were reviewed. RESULTS: In 31 cases a correct
      CD was made based on the cytologic and immunocytochemical (IM) findings. The MAMs
      were characterized by abundant dyshesive pleomorphic malignant cells containing
      prominent nucleoli and occasional intranuclear cytoplasmic inclusions. The tumor
      cells stained positively with S-100 and/ or HMB-45 antibodies. There were four
      cases with unusual cytologic manifestations and equivocal IM characteristics
      requiring electron microscopic examination (EME) of the aspirated tumor cells to
      identify intracytoplasmic melanosomes, pre-melanosomes, or microtubules within
      cisternae of rough endoplasmic reticulum (MCRER) to establish a diagnosis of MAM.
      CONCLUSIONS: A correct CD of MAMs may be made in a large number of cases by
      routine cytologic findings and IM staining with S-100 protein and HMB-45
      antibodies. However, EME is necessary to demonstrate melanosomes, premelanosomes,
      or MCRER in cases with unusual cytologic and equivocal IM manifestations.

PMID- 9570212
TI  - Utilization of core wash material in the diagnosis of breast lesions by
      stereotactic needle biopsy.
AB  - BACKGROUND: Several reports have compared the results of fine-needle aspiration
      and stereotactic core needle biopsy in nonpalpable breast lesions. In this study
      the authors describe a simple method to retrieve cytologic material from a core
      breast biopsy sample that provides the diagnosis within 1 hour of the procedure.
      METHODS: Two hundred and eleven nonpalpable breast lesions were biopsied. Each
      core needle biopsy sample was placed in a mesh bag, and the bag and needle notch
      were washed in Cytolyt solution to obtain a monolayer using a commercial ThinPrep
      processor. The cytologic diagnoses were divided into four categories: benign,
      suspicious, malignant, and unsatisfactory, which then were compared with core
      needle biopsy results. RESULTS: Cytology reports of 211 lesions were as follows:
      169 lesions (80%) were benign, 16 lesions (7.6%) were suspicious, 11 lesions
      (5.2%) were malignant, and 15 lesions (7.1%) were unsatisfactory. Core needle
      biopsy showed 165 of 169 samples (98%) to be benign and 4 to be malignant. Of the
      16 suspicious smears, 10 were invasive carcinoma, 2 were in situ lesions, 3 were
      hyperplasias, and 1 was fibrosis. Of the 11 malignant smears, 10 were confirmed
      on core needle biopsy and 1 was read as atypia on the first core needle biopsy
      sample and malignant on a second, separate, follow-up core needle biopsy. Of the
      15 unsatisfactory samples, 14 were found to be benign and 1 was found to be
      malignant on a separate, follow-up core needle biopsy. CONCLUSIONS: The core wash
      technique was 85% sensitive and 98% specific for malignancy. Only 7% of specimens
      were insufficient for diagnosis, and 93% of these were proven to be benign. This
      technique is useful for immediate (within 1 hour) diagnosis of breast lesions,
      alleviating patient anxiety and supplementing the diagnostic yield of the core
      biopsy.

PMID- 9570213
TI  - Utility of the antibodies CA 19-9, HBME-1, and thrombomodulin in the diagnosis of
      malignant mesothelioma and adenocarcinoma in cytology.
AB  - BACKGROUND: The distinction between malignant mesothelioma (MM) and
      adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often
      requiring immunocytochemistry to support the diagnosis. Recent reports have
      proposed the utilization of antibodies to mesothelial cell clone HBME-1 and
      thrombomodulin (TM), because they are immunoreactive in MM and less commonly
      reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19-9 has been
      observed in many ACAs and reportedly is absent in MM. METHODS: In this study,
      immunostaining was performed on formalin fixed, paraffin embedded cell blocks
      from effusions or fine-needle aspirations using the avidin-biotin-peroxidase
      method. Thirty-eight MMs and 49 ACAs were tested using antibodies to CA 19-9,
      HBME-1, and TM. RESULTS: Anti-CA 19-9 stained only 1 of the 37 cases of MM tested
      (3%), but stained 24 of the 49 cases of ACA (49%). Anti-HBME-1 stained 34 of 38
      cases of MM (89%), and 28 of 43 cases of ACA tested (65%). Anti-TM stained 24 of
      36 cases of MM (67%), and 21 of 40 cases of ACA tested (53%). CONCLUSIONS: CA 19
      9 has utility as part of an immunocytochemical panel for distinguishing ACA from
      MM, because a positive staining reaction would make the diagnosis of MM unlikely.
      Although HBME-1 and TM can identify MM positively, each frequently is detected in
      ACA, thus limiting the utility of these antibodies in cytologic specimens.

PMID- 9570214
TI  - nm23 protein expression in fine-needle aspirates from breast carcinoma: inverse
      correlation with cytologic grading, lymph node status, and ploidy.
AB  - BACKGROUND: nm23 has been recognized as a potential suppressor gene of
      metastasis. Reduced nm23 expression in breast carcinoma has been found to
      correlate with axillary lymph node metastases, high grade tumors, and shorter
      survival. METHODS: nm23 protein was detected immunocytochemically using an avidin
      biotin complex technique. When a few cells showed negative or marked reduced
      cytoplasmic staining, expression was considered reduced. Cytologic grading was
      performed on routine fine-needle aspirates (FNAC). Ploidy was determined by in
      situ hybridization of chromosomes 6, 7, 12, and 17 on interphase cell nuclei from
      FNAC. When all four chromosomes revealed a disome pattern, the tumor was
      classified as diploid; mixed disome/aneusome carcinomas as well as those with
      aneusomy in all four chromosomes were considered aneuploid. RESULTS:
      Approximately 83% of specimens had reduced expression of nm23 protein. Forty-four
      of 45 lymph node positive tumors as well as 27 of 29 aneuploid tumors, were found
      to have reduced nm23 expression. Likewise, 49 of 57 Grade 2 (G2) carcinomas (86%)
      and 20 of 22 Grade 3 (G3) carcinomas (91%) showed reduced nm23 expression. Twenty
      nine of 39 Grade 1 (G1) carcinomas (74%) had reduced nm23 expression. None of the
      G1 or G2 tumors with full nm23 expression had axillary lymph node metastases.
      CONCLUSIONS: nm23 protein showed a significant inverse correlation with lymph
      node status, cytologic grading, and ploidy. The nm23 protein antibody may have
      potential as a preoperative marker in identifying subgroups of patients who
      either may have a worse prognosis than expected (e.g., those with G1 carcinomas
      with reduced nm23 expression) or who may be able to avoid axillary lymph node
      dissection (e.g., those with G1 carcinoma with full nm23 protein expression).
      Cancer

PMID- 9570215
TI  - Morphometry in the cytologic evaluation of thyroid follicular lesions.
AB  - BACKGROUND: The current study was undertaken to evaluate the quantitative
      estimation of cytologic features on aspirated smears for the preoperative
      differential diagnosis of follicular lesions of the thyroid. METHODS: The
      subjects were 60 patients with follicular lesions of the thyroid (including 20
      follicular carcinomas, 15 follicular adenomas, and 25 adenomatous goiters) whose
      histopathologic explorations were conducted fully postoperatively. Using a
      microscope connected to a computerized video system, the mean nuclear area, the
      mean nuclear perimeter, the circular rate, the largest to the smallest dimension
      ratio (LS ratio) of the nuclei, and the coefficient of variation of the nuclear
      area (NACV) were measured and analyzed. RESULTS: Among the quantitative
      morphometric parameters of nuclei, the circular rate was significantly higher in
      the group with adenomatous goiters than those with follicular carcinomas (P <
      0.00001) and adenomas (P < 0.005). The group with follicular carcinomas had a
      higher LS ratio than the group with adenomatous goiters (P < 0.0005). The NACV
      value increased as the malignant potential of the lesion increased and showed
      significant differences between the groups. When a NACV of 21.5% was chosen as
      the cutoff point, the incidence of malignancy was significantly higher in
      patients with high NACV values than in those with low NACV values (P < 0.00001).
      Using this borderline value, it was possible to distinguish malignant from benign
      diseases with a sensitivity of 85.0%, a specificity of 82.5%, and an accuracy of
      83.3%. CONCLUSIONS: Preoperative quantitative estimations of cytologic nuclear
      features are useful for the preoperative differential diagnosis of follicular
      lesions of the thyroid.

PMID- 9570216
TI  - Image cytometry as a discriminatory tool for cytologic specimens obtained by
      endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND: Routine brush cytology is relatively insensitive for the diagnosis of
      biliary and pancreatic malignancy. Sensitivity can be improved by measuring DNA
      and proliferation. The goal of this study was to assess the discriminatory
      capacity of image cytometry using pancreaticobiliary brush cytology specimens
      obtained during endoscopic retrograde cholangiopancreatography (ERCP). Analysis
      included morphometry, DNA quantification, and characterization of nuclear
      chromatin distribution and condensation. METHODS: Brush cytology specimens were
      obtained during ERCP from 22 chronic pancreatitis specimens, 11 pancreatic
      adenocarcinoma specimens, 13 primary sclerosing cholangitis specimens, and 11
      cholangiocarcinoma specimens and contrasted with 25 normal epithelia specimens. A
      SAMBA 2005 image processor was used to analyze Feulgen stained chromatin density
      and distribution. Discriminant analysis of 37 morphonuclear variables was
      performed to characterize differences between: 1) chronic pancreatitis and
      pancreatic adenocarcinoma, and 2) primary sclerosing cholangitis and
      cholangiocarcinoma. RESULTS: Chronic pancreatitis was distinguished from
      pancreatic adenocarcinoma (P < or = 0.001); sensitivity and specificity were both
      estimated to be 82%. Primary sclerosing cholangitis was distinguished from
      cholangiocarcinoma (P < or = 0.01); sensitivity and specificity were estimated to
      be 82% and 85%, respectively. CONCLUSIONS: Multiparameter image cytometry has
      potential as an adjuvant diagnostic technique in patients with pancreaticobiliary
      malignancy.

PMID- 9570217
TI  - A functional comparison of animal anterior cruciate ligament models to the human
      anterior cruciate ligament.
AB  - Many investigators have used animal models to clarify the role of the human
      anterior cruciate ligament (ACL). Because none of these models are anatomically
      and biomechanically identical to the human ACL, there exists a need for an
      objective comparison of these models. To do this, we used a universal force
      moment sensor to measure and compare the in situ forces, including magnitude and
      direction, of the ACL and the anteromedial (AM) and posterolateral (PL) bundles
      of human, pig, goat, and sheep knees. An Instron was used to apply 50 and 100 N
      anterior tibial loads at 90 degrees of knee flexion, while a universal force
      moment sensor was used to measure the forces applied by the ACL to the tibia, the
      in situ force of the ACL. We found significant differences between the magnitude
      of force experienced by the goat and sheep ACL and AM and PL bundles when
      compared with the human ACL and AM and PL bundles. Also, the direction of the in
      situ force in the ACL and AM bundles of the goat and sheep were different from
      the human. The pig knee differed from the human only in the magnitude and
      direction of the in situ force in the PL bundle in response under anterior tibial
      loading. A tally of the significant differences between the animal models and the
      human knees indicates that goat and sheep knees may have limitations in modeling
      the human ACL, while the pig knee may be the preferred model for experimental
      studies.

PMID- 9570218
TI  - In vivo kinematics of the rabbit knee in unstable models of osteoarthrosis.
AB  - The effects of osteoarthrosis inducing surgery on the kinematics of the rabbit
      knee were evaluated in vivo. A video motion analysis system was used to track
      reflective markers attached to two pins fixed in both femur and tibia, and from
      these data knee kinematics were computed. The control for all measurements was
      the gait after pins were implanted, but the knee was unaltered. Both a release of
      the anterior cruciate ligament and a partial medial meniscectomy were then
      performed, and the animals' gait was recorded at 4, 8 and 12 weeks after knee
      surgery. Knee kinematics were described by three translations and three rotations
      and were analyzed in terms of maximum and minimum values and range of motion.
      Statistical comparisons of these data between control and operated knees were
      made using Wilcoxon's signed rank test. Results showed an initial increase in
      maximum anterior displacement which returned to normal after 12 weeks. In
      addition there was a persistent increase in knee adduction and an increase in the
      minimum value of external rotation over the 12 week period. At 12 weeks after
      surgery there was no change in range of any measurable kinematic parameter.
      Overall, the changes in joint kinematics following partial medial meniscectomy
      and release of the anterior cruciate ligament were small, suggesting that altered
      joint kinematics might not be a critical factor in the development of
      osteoarthrosis in this animal model.

PMID- 9570219
TI  - Axial vibration of threaded external fixation pins: detection of pin loosening.
AB  - The hypothesis of this study was that a nondestructive vibrational method could
      detect bone lysis at the external fixation pin-bone interface prior to current
      clinical and radiographic methods. In vitro models were used to simulate changes
      observed during pin loosening in vivo. Fixation pin axial natural frequency
      decreased with decreasing tensile modulus of the material into which it was
      implanted. In a live animal study the right tibia of 12 dogs was fractured and
      stabilized with a four-pin unilateral external fixation frame. The axial natural
      frequency of each pin was measured and radiographs were taken at 0, 2, 4, 6, 8,
      and 10 weeks after surgery. The natural frequency did not change when the first
      radiographic changes around the interface were observed. Pins were palpably
      stable at this point. As loosening progressed, the natural frequency did
      decrease. Frequency and quasistatic tests of dissected pin-bone structures
      revealed a good correlation between natural frequency and pin-bone interface
      stiffness. In addition, the measurement of natural frequency was more sensitive
      to bone structure changes at the pin-bone interface than low-load quasi-static
      stiffness. Therefore, a nondestructive vibration technique could be used instead
      of low-load quasistatic tests for assessing the pin-bone interface ex. vivo.

PMID- 9570221
TI  - Mechanical characterization of an in vitro device designed to quantitatively
      injure living brain tissue.
AB  - Due to the nonlinear, viscoelastic material properties of brain, its mechanical
      response is dependent upon its total strain history. Therefore, a low strain
      rate, large strain will likely produce a tissue injury unique from that due to a
      high strain rate, moderate strain. Due to a lack of current understanding of
      specific in vivo physiological injury mechanisms, a priori assumptions cannot be
      made that a low strain rate injury induced by currently employed in vitro injury
      devices is representative of clinical, nonimpact, inertial head injuries. In the
      present study, an in vitro system capable of mechanically injuring cultured
      tissue at high strain rates was designed and characterized. The design of the
      device was based upon existing systems in which a clamped membrane, on which
      cells have been cultured, is deformed. However, the present system incorporates
      three substantial improvements: (1) noncontact measurement of the membrane
      deflection during injury; (2) precise and independent control over several
      characteristics of the deflection; and (3) generation of mechanical insults over
      a wide range of strains (up to 0.65) and strain rates (up to 15 s[-1]). Such a
      system will be valuable in the elucidation of the mechanisms of mechanical trauma
      and determination of injury tolerance criteria on a cellular level utilizing
      appropriate mechanical injury parameters.

PMID- 9570220
TI  - Muscle-tendon model with length history-dependent activation-velocity coupling.
AB  - We developed muscle-tendon models incorporating Hill-type structure and length
      dependent coupling between activation and velocity. The models were evaluated in
      electrically stimulated cat soleus muscles. Dynamic model parameters were
      estimated by a nonlinear parameter estimation algorithm from input-output data
      obtained during simultaneous random stimulation and length changes. Static
      parameters were estimated from the length-tension curve. A model with length
      history-dependent activation-velocity coupling predicted the behavior of the
      muscle under a wide variety of conditions, including during random perturbations
      and during isovelocity movements, where it captured short range stiffness and
      length history-dependent postyielding behavior. Furthermore, the model predicted
      twitch responses. The generality of this fixed parameter model makes it
      especially suitable for simulation and feedforward control, where muscle
      responses are not available for on-line parameter adaptation.

PMID- 9570222
TI  - Geometrical risk factors for atherosclerosis in the femoral artery: a
      longitudinal angiographic study.
AB  - In order to study the evolution of atherosclerosis in the superficial femoral
      artery in relation to local factors of vascular geometry, image processing of
      digitized angiograms was carried out in 237 hyperlipidemic patients before and
      after a three-year period of lipid-lowering treatment. The degree of
      atherosclerosis was measured as edge roughness, which was calculated separately
      for inner curves, outer curves, and straight segments and, in a subgroup of 110
      patients, for segments with and without branches on either side of the artery.
      Initially, inner curves had significantly higher roughness values than outer
      curves, and outer curves higher than straight segments. After three years, there
      was an increase of borderline significance in the outer curves, and the
      difference between inner and outer curves was no longer significant. In several
      subpopulations, the increase in outer curve roughness was clearly significant.
      When branched and nonbranched segments were compared, the only significant
      difference was at the second examination where segments with a lateral branch had
      higher roughness of the medial edge than those without such a branch. It is
      concluded that curves are more likely than bifurcations to constitute a geometric
      risk factor for atherosclerosis, but it remains to explain the causal mechanism
      for this factor.

PMID- 9570224
TI  - Assessment of strain field in endothelial cells subjected to uniaxial deformation
      of their substrate.
AB  - A stretch chamber has been developed in order to visualize the deformation of
      cells subjected to controlled uniaxial stretch of their substrate. A rectangular,
      custom-made, transparent silicone channel is used as a deformable substrate.
      Bovine aortic endothelial cells are plated at the bottom of the channel whose
      lateral deformation is controlled by two piezoelectric translators. The system is
      mounted on the stage of a confocal microscope where three-dimensional (3D) images
      of the cells can be acquired simultaneously in the three RGB channels. The first
      channel provides images of 216 nm fluorescent beads embedded in the cytoskeleton
      (used as internal markers). The second is used to image the shape of the nucleus
      revealed by live cell nucleic acid staining. The third one provides a transmitted
      light image of the cell outline. 3D images of the cell are taken before
      deformation, after uniaxial deformation of the substrate (up to 25%) and after
      relaxation. Results indicate that: (a) the cell closely follows the deformation
      imposed by the substrate with no measurable residual strain after relaxation, and
      (b) there is a clear mechanical coupling between the extracellular matrix and the
      nucleus, which deforms significantly under the applied substrate stretch.
      Suggesting that the nucleus can directly sense the mechanical environment of the
      cell, the latter result has potentially important implications for signal
      transduction.

PMID- 9570223
TI  - Bioresorbable microporous stents deliver recombinant adenovirus gene transfer
      vectors to the arterial wall.
AB  - The use of intravascular stents as an adjunct for percutaneous transluminal
      revascularization is limited by two principal factors, acute thrombosis and
      neointimal proliferation, resulting in restenosis. To overcome these limitations,
      we have investigated the potential of microporous bioresorbable polymer stents
      formed from poly(L-lactic acid) (PLLA)/poly(epsilon-caprolactone) (PCL) blends to
      function both to provide mechanical support and as reservoirs for local delivery
      of therapeutic molecules and particles to the vessel wall. Tubular PLLA/PCL
      stents were fabricated by the flotation-precipitation method, and helical stents
      were produced by a casting/winding technique. Hybrid structures in which a
      tubular sheath is deposited on a helical skeleton were also generated. Using a
      two-stage solvent swelling technique, polyethylene oxide has been incorporated
      into these stents to improve hydrophilicity and water uptake, and to facilitate
      the ability of these devices to function as drug carriers. Stents modified in
      this manner retain axial and radial mechanical strength sufficient to stabilize
      the vessel wall against elastic recoil caused by vasoconstrictive and mechanical
      forces. Because of the potential of direct gene transfer into the vessel wall to
      ameliorate thrombosis and neointimal proliferation, we have investigated the
      capacity of these polymer stents to function in the delivery of recombinant
      adenovirus vectors to the vessel wall. In vitro, virus stock was observed to
      readily absorb into, and elute from these devices in an infectious form, with
      suitable kinetics. Successful gene transfer and expression has been demonstrated
      following implantation of polymer stents impregnated with a recombinant
      adenovirus carrying a nuclear-localizing betaGal reporter gene into rabbit
      carotid arteries. These studies suggest that surface-modified polymer stents may
      ultimately be useful adjunctive devices for both mechanical support and gene
      transfer during percutaneous transluminal revascularization.

PMID- 9570225
TI  - Optical and radioisotope indicator dilution measurements in pulmonary edema.
AB  - The objective of this study was a validation of an optical multiple indicator
      dilution technique for measuring microvascular exchange parameters in edematous
      lungs by comparison to conventional radioisotope multiple indicator dilution
      methods. Six anesthetized dogs were studied at baseline and after alloxan
      infusion to increase capillary permeability. In addition, 11 isolated, perfused
      dog lungs were studied at baseline and after edema was created by increasing
      venous pressure or by infusing alloxan to increase vascular permeability.
      Increased capillary permeability from alloxan infusion led to increases in most
      but not all capillary exchange parameters as analyzed by mathematical models and
      measured by both optical and radioisotope methods. Increased vascular pressure
      led to increased edema but no significant increases in capillary exchange
      parameters. Two-way analysis of variance (ANOVA; variations in baseline versus
      pressure or alloxan and variation in optical versus radioisotope for each
      transport parameter derived from the mathematical models) indicated few
      significant differences in capillary exchange parameters between optical and
      radioisotope measures. Newman-Keuls multiple comparison tests did uncover some
      variations between a few of the group-mean values derived from optical and
      radioisotope methods. However, optical and radioisotope parameter measurements
      were highly correlated for all studies regardless of the mathematical model used
      for analysis.

PMID- 9570226
TI  - In vivo measurement of real-time aortic segmental volume using the conductance
      catheter.
AB  - The goal of this investigation was to determine if the conductance catheter
      technique for chamber volume measurement could be applied in vivo to determine
      real-time phasic aortic segmental volume. A four-electrode conductance catheter
      was used to measure time-varying resistance of the descending thoracic aorta in
      open-chest, anesthetized dogs. Resistance was converted to segmental volume and
      the slope correction factor (alpha) and parallel conductance volume (Vp) were
      determined. The results showed excellent linear correlation between conductance
      and sonomicrometric segmental volume. The correction factors alpha and Vp were
      found to be empirically related to average vessel diameter. The relatively high
      values for the slope correction factor (alpha=4.59+/-0.17 SEM) were found to be
      primarily related to low-resistivity shunt paths probably originating in the
      periadventitial aortic wall and to a lesser extent to changes in flow-induced
      increases in blood resistivity, hematocrit, catheter position, and other adjacent
      tissue resistivity. The results demonstrate that correction factors empirically
      derived from measurements of mean aortic diameter could be used to determine
      absolute real-time phasic segmental volume, cross-sectional area, or diameter.
      The conductance technique may possess the same potential for determining aortic
      mechanical properties which has already been demonstrated for determining
      ventricular mechanical properties.

PMID- 9570227
TI  - An engineering model of dynamic cardiomyoplasty. I.
AB  - Dynamic cardiomyoplasty (DCM) is an emerging surgical procedure for heart failure
      in which the patient's latissimus dorsi (LD) muscle is wrapped around the heart
      and stimulated to contract in synchrony with the heartbeat as a cardiac assist
      measure. A 6 week training protocol of progressive electrical stimulation renders
      the normally fatigueable skeletal muscle fatigue-resistant and suitable for
      chronic stimulation. To date, over 500 procedures have been performed in
      worldwide clinical trials. Investigators typically report symptomatic improvement
      and modest hemodynamic improvement in patients. Controversy exists regarding the
      exact mechanism of DCM. To test the hypothesis that DCM augments cardiac stroke
      volume through improvement in systolic function, we formulated an engineering
      model of dynamic cardiomyoplasty to predict stroke volume. The heart and the LD
      were modeled as nested (series) elastance chambers, and the vasculature was
      represented by a two-element Windkessel model. Using five healthy goats, we
      verified model predictions of stroke volume for both stimulator ON beats (y =
      1.00x-0.08, r = 0.87, p < 0.0001) and OFF beats (y = 1.01x+1.06, r = 0.91, p <
      0.0001), where x and y are the measured and predicted stroke volumes,
      respectively. The model confirms that using untrained latissimus dorsi applied to
      the normal myocardium produces only moderate increases in stroke volume and
      suggests that future research should focus on increasing LD strength after
      training.

PMID- 9570228
TI  - An engineering model of dynamic cardiomyoplasty. II. Clinical applications.
AB  - Previously, a modification to the Sunagawa engineering model for the isolated
      left ventricle and arterial system was proposed and validated for dynamic
      cardiomyoplasty in an acute goat preparation. To test the hypothesis that this
      model may be applied to the clinical scenario in cardiomyoplasty patients, we
      predicted human stroke volume using the model with human clinical data from the
      literature. Predicted stroke volume correlated well with published stroke volume
      in patients who have had the dynamic cardiomyoplasty procedure. These results
      suggest that the modest hemodynamic improvement commonly reported after the
      procedure is performed may be due to diminished latissimus dorsi strength after
      transformation. The validity of both the original Sunagawa model and the
      previously proposed modification for dynamic cardiomyoplasty is further supported
      with these results. A nomogram methodology for predicting stroke volume after
      dynamic cardiomyoplasty for any particular patient is presented.

PMID- 9570229
TI  - Real time signal processing in the clinical setting.
AB  - We routinely use a variety of real time signal acquisition, enhancement, and
      display techniques in the operating room to provide the surgeon with functional
      information. This enables reduction of surgical morbidity in cases which present
      a significant risk to the nervous system. Here we present regression based signal
      processing algorithms which produce considerable signal-to-noise-ratio
      enhancement with corresponding reduction in the time required to obtain an
      interpretable neurophysiological signal. We also present the approach we have
      applied to fault tolerance and distributed data display for our workstation
      cluster environment.

PMID- 9570230
TI  - Intrinsic oscillations and discharge regularity of units in the dorsal cochlear
      nucleus (DCN) of the barbiturate anesthetized gerbil.
AB  - Spike discharge patterns showing intrinsic oscillations (IOs) have been reported
      in units in the dorsal cochlear nucleus (DCN) of the decerebrate cat. These
      oscillations are related to the regularity of a unit's discharge rate and may be
      important for pitch perception. A DCN unit's regularity can be affected by
      several factors including: synaptic architecture, cell membrane properties, and
      the auditory nerve discharge rate. Responses to multiple presentations of short
      duration tone bursts (200 ms duration, 1 s trial) at the unit's best frequency
      (BF) at 20 dB re threshold were recorded from 297 units in the DCN of the
      barbiturate-anesthetized gerbil. Comparisons of unit regularity properties and IO
      properties are shown. The relative power spectrum (Fourier transform of the
      autocorrelogram normalized by the average rate) was used to quantify IO
      properties. Most units (84%) exhibited IOs in their sustained discharge rate.
      With the exception of Onset units and most bursting units, the mean inter-spike
      interval was correlated with the IO frequency and the coefficient of variation
      was correlated with the IO magnitude. These results suggest that stimulus
      encoding mechanisms utilizing IOs may depend on the temporal evolution of the
      units' regularity properties.

PMID- 9570231
TI  - Sensitivity analysis of kernel estimates: implications in nonlinear physiological
      system identification.
AB  - Many techniques have been developed for the estimation of the Volterra/Wiener
      kernels of nonlinear systems, and have found extensive application in the study
      of various physiological systems. To date, however, we are not aware of methods
      for estimating the reliability of these kernels from single data records. In this
      study, we develop a formal analysis of variance for least-squares based nonlinear
      system identification algorithms. Expressions are developed for the variance of
      the estimated kernel coefficients and are used to place confidence bounds around
      both kernel estimates and output predictions. Specific bounds are developed for
      two such identification algorithms: Korenberg's fast orthogonal algorithm and the
      Laguerre expansion technique. Simulations, employing a model representative of
      the peripheral auditory system, are used to validate the theoretical derivations,
      and to explore their sensitivity to assumptions regarding the system and data.
      The simulations show excellent agreement between the variances of kernel
      coefficients and output predictions as estimated from the results of a single
      trial compared to the same quantities computed from an ensemble of 1000 Monte
      Carlo runs. These techniques were validated with white and nonwhite Gaussian
      inputs and with white Gaussian and nonwhite non-Gaussian measurement noise on the
      output, provided that the output noise source was independent of the test input.

PMID- 9570232
TI  - A novel method for efficient drug delivery.
AB  - Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve
      high concentrations of agents which may be rapidly degraded systemically or which
      exhibit very short half-lives in vivo. In this article, the operating
      characteristics of a novel local drug delivery method are described and its
      effectiveness demonstrated computationally and experimentally. Computational
      models used a finite volume method to determine the concentration field. Optical
      dye density measurements of Evans blue in saline were performed in an in vitro
      steady flow system. Modeling parameters were kept in the physiologic range.
      Experimental flow visualization studies demonstrated high concentrations of
      infusate near the vessel wall. Computational studies predicted high, clinically
      significant drug concentrations along the wall downstream of the infusion device.
      When the radial infusion velocity is large (infusion flow rate, Qinf>0.5% of the
      main flow rate, Q), the wall concentration of the infused drug remains high,
      e.g., levels are greater than 80% of the infusate concentration 5 cm downstream
      of the infusion device. At lower infusion rates (Qinf<0.001Q), the drug
      concentration at the wall decreases exponentially with axial distance to less
      than 25% of the infusate concentration 5 cm downstream of the infusion device,
      although therapeutic drug levels are still readily maintained. The near wall drug
      concentration is a function of flow conditions, infusion rate, and the drug
      diffusivity. Good agreement was obtained between computational and experimental
      concentration measurements. Flow simulation and experimental results indicate
      that the technique can effectively sustain high local drug concentrations for
      inhibition of thrombosis and vascular lesion formation.

PMID- 9570233
TI  - Familial case of choledochocele.

PMID- 9570234
TI  - Accidental transmission of HCV and treatment with interferon.
AB  - Accidental transmission of contagious pathogens, especially hepatitis C virus
      (HCV), by needlestick or other means as an occupational hazard for medical staff
      is of concern. We retrospectively analysed cases of work-related accidental
      injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human
      immunodeficiency virus (HIV) reported to the centres for disease control at 15
      hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to
      August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an
      incidence of 0.2-3.5 accidents per month per hospital. Such accidents occurred in
      297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians,
      four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one
      secretary and two others. There were 323 (77.6%) injuries caused by needlestick,
      42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood
      splatters from patients into the eyes or mouth, 10 (2.4%) from contact with
      injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were
      HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four
      cases (1.6%) of HCV infection were found and treated with one or two courses of
      interferon therapy, and HCV was subsequently cleared. All four patients were
      cured with interferon therapy. None of the HBV-injured cases resulted in
      infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine.
      No HIV or syphilis infection was contracted. In summary, chronic HCV infection
      acquired as an occupational hazard can be cured by appropriate treatment, such as
      with interferon, after early detection of the infection.

PMID- 9570235
TI  - Preliminary report of a randomized, double-blind placebo-controlled trial of a
      Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis
      C.
AB  - The treatment of chronic hepatitis C is relatively unsatisfactory and many
      patients have turned to unproven alternative medicines to modify the course of
      their illness. We report a study of a Chinese herbal medicine preparation CH-100
      in the management of chronic hepatitis C. Patients with documented chronic
      hepatitis C were randomly allocated to receive active herbal or placebo tablets
      (five tablets thrice daily). Patients were followed monthly and evaluated by a
      Western and a traditional Chinese medical practitioner. Therapy was monitored by
      measurement of liver function tests, creatinine and full blood count on a monthly
      basis. Twenty patients in each group were well matched for age, sex, duration of
      illness, previous interferon therapy and alcohol intake. Active Chinese herbal
      medication was associated with a significant reduction in alanine
      aminotransferase (ALT) levels over the 6 month study period (P < 0.03). No
      patient cleared the virus but four normalized their ALT on treatment.
      Appropriately prescribed Chinese herbal medicine may have a role in the
      management of chronic hepatitis C and further controlled studies are indicated.

PMID- 9570236
TI  - Cryoglobulinaemia among maintenance haemodialysis patients and its relation to
      hepatitis C infection.
AB  - It has been shown that hepatitis C virus (HCV) infection is closely associated
      with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant
      among chronic haemodialysis patients. We studied 531 renal failure patients on
      maintenance dialysis including 170 with positive HCV antibodies for
      cryoglobulinaemia, and its incidence was compared with controls which consisted
      of 242 chronic hepatitis C patients without renal failure and 183 healthy adults.
      Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection,
      10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic
      hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new
      renal failure patients who were started on dialysis within 6 months, four were
      positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV
      negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among
      dialysis patients were much lower than those of the control cases and other
      reports on non-dialysis cases. Patients with cryoglobulinaemia were generally
      younger compared with patients negative for this condition. There was no
      correlation between cryoglobulinaemia and past blood transfusion, underlying
      disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal
      failure at relatively young ages and a considerable proportion of
      cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the
      time of the start of haemodialysis. There was no indication that the presence of
      cryoglobulin in serum adversely affects the liver disease nor increases serum
      virus load in HCV-infected dialysis patients. Thus, it was concluded that
      although HCV infection has a certain role in the development of cryoglobulinaemia
      in dialysis patients, they develop cryoglobulinaemia less frequently and produce
      cryoglobulin to a lesser degree in the presence of HCV infection as compared with
      non-dialysis patients.

PMID- 9570237
TI  - High prevalence of hepatitis G virus infection in multiply transfused children
      with thalassaemia.
AB  - We investigated the prevalence of hepatitis G virus (HGV) RNA in relation to the
      frequency of blood transfusions in thalassaemic children and in volunteer blood
      donors in Thailand. Furthermore, we studied the frequency of coinfection with
      hepatitis B virus (HBV) and/or hepatitis C virus (HCV) as well as a possible
      relationship to the alanine aminotransferase (ALT) status of the blood samples,
      taken at random from thalassaemic children who have received multiple blood
      transfusions and from volunteer blood donors. The results show detectable HGV-RNA
      in 32.6% of transfusion patients and in 5% of blood donors. The prevalence of HGV
      RNA peaked between the 11th and 50th transfusion. The relationship between HGV
      infection and ALT status was not statistically relevant.

PMID- 9570238
TI  - Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a
      prognostic marker in patients with primary biliary cirrhosis.
AB  - It has been reported that the presence of anti-nuclear antibody against a 210 kDa
      glycoprotein of nuclear pore complex (anti-gp210) is highly specific for primary
      biliary cirrhosis (PBC). The aim of the present study was to investigate the
      significance of anti-gp210, especially as a prognostic marker. The presence of
      anti-gp210 was ascertained in 113 patients with PBC and 162 controls by indirect
      immunofluorescence assay using HepG2 cells and immunoblotting analysis using
      nuclear extracts from HeLa cells. Anti-gp210 was detected in 25 of the 113
      (22.1%) patients. None of the 162 controls was positive for anti-gp210. The
      appearance and titre of anti-gp210 in the patients with PBC did not vary from the
      time of diagnosis and through their clinical course. Anti-mitochondrial
      antibodies (AMA), including antibodies against pyruvate dehydrogenase complex,
      branched chain alpha-ketoacid dehydrogenase complex and alpha-ketoglutarate
      dehydrogenase complex, were not detected by enzyme-linked immunosorbent assay in
      five of the 113 (4.4%) patients with PBC. However, anti-gp210 alone was positive
      in one of these five patients. The difference in prognosis was statistically
      significant; patients with PBC positive for anti-gp210 died from hepatic failure
      more frequently than those who were negative (P < 0.01), although there were no
      statistically significant differences in the frequency of jaundice and the
      histological stage at the time of diagnosis between the two groups. We suggest
      that the presence of anti-gp210 is one of the independent prognostic markers able
      to predict, at the time of diagnosis, a poor outcome in patients with PBC.

PMID- 9570239
TI  - Haemodynamic effects of chronic octreotide and tetrandrine administration in
      portal hypertensive rats.
AB  - Octreotide is an effective portal hypotensive drug in the control of variceal
      bleeding. Tetrandrine is a type of calcium channel blocker recently reported to
      reduce portal hypertension. The present study was undertaken to investigate the
      haemodynamic effects of octreotide and tetrandrine, alone and in combination, in
      portal hypertensive rats. Portal hypertension was induced by partial portal vein
      ligation. Portal hypertensive rats were allocated into one of the four groups:
      vehicle group (saline, 0.5 mL/day), octreotide group (100 microg/kg per 12 h),
      tetrandrine group (20 mg/kg per 12 h), and octreotide (100 microg/kg per 12 h)
      plus tetrandrine (20mg/kg per 12 h) group. Tetrandrine or saline was administered
      by gavage, and octreotide by subcutaneous injection. The drug was given for 8
      consecutive days, starting 1 day before ligation and continuing onwards.
      Haemodynamic parameters were measured thereafter, using the radioactive
      microsphere method. The portal venous pressure and portal tributary blood flow
      were significantly reduced, while portal territory and renal vascular resistances
      were significantly enhanced, by octreotide, tetrandrine, or octreotide plus
      tetrandrine in portal hypertensive rats, compared with the vehicle group. Our
      results showed that long-term administration of octreotide, tetrandrine, or
      octreotide plus tetrandrine led to portal hypotensive effects in portal
      hypertensive rats, but octreotide alone exerted better anti-hyperdynamic effects
      compared with tetrandrine alone. A combination of octreotide and tetrandrine
      offered no major beneficial anti-hyperdynamic effects compared with octreotide
      alone.

PMID- 9570240
TI  - Ki-67 expression as a prognostic marker in patients with hepatocellular
      carcinoma.
AB  - Ki-67 expression in tumours has been shown to be associated with prognosis in
      patients with hepatocellular carcinoma (HCC). In this study, primary HCC samples
      were obtained from 67 patients undergoing surgical resection. None of these
      patients had been subjected previously to any other form of therapy, such as
      arterial embolization or chemotherapy. Histologically normal liver tissues from
      liver resection for metastatic colon cancer were taken as controls (n = 8).
      Monoclonal antibody against Ki-67 was used for immunostaining and flow cytometry
      was used to measure tumour DNA ploidy. The mean Ki-67 labelling index (percentage
      of Ki-67-positive cells) of the HCC (26 +/- 22%; range 0.1-89%) was significantly
      higher than that of the normal controls (39 +/- 0.8%, P < 0.05). The mean Ki-67
      labelling index (19 +/- 15%; n = 28) of the tumours with diploid DNA pattern was
      significantly lower than those with aneuploid DNA pattern (32 +/- 25%, n = 39; P
      = 0.01). Hepatocellular carcinoma patients (n = 47) with Ki-67 index > 10% had a
      significantly lower disease-free and overall survival than those (n = 20) with Ki
      67 index < or = 10% (P = 0.0009 and P = 0.02, respectively). Multivariate
      analysis showed that Ki-67 expression and tumour node metastasis stage were two
      independent prognostic factors for disease-free and overall survival rates. Our
      results suggest that the expression of Ki-67 is an independent prognostic
      indicator for patients with HCC after resection and could be of assistance in the
      decision-making of adjuvant therapy.

PMID- 9570241
TI  - Economic evaluation of Helicobacter pylori eradication for the treatment of
      duodenal ulcer disease in Japan: a decision analysis to assess eradication
      strategy in comparison with a conventional strategy.
AB  - To evaluate the socio-economic effects of Helicobacter pylori eradication in the
      treatment of duodenal ulcer disease in Japan, a clinical decision analysis was
      performed to assess H. pylori eradication therapy compared with the conventional
      strategy of maintenance with histamine-2 receptor antagonists. A decision tree
      based state transition model (Markov chain approach) implemented to simulate a 5
      year period of follow up was constructed. The H. pylori eradication strategy was
      found to be superior to the conventional maintenance strategy with regard to
      clinical effectiveness and other dimensions of a patient's outcome. Furthermore,
      in a long-term perspective, the eradication strategy was less costly than the
      maintenance strategy. Helicobacter pylori eradication should be recommended as
      the first choice treatment of H. pylori-positive duodenal ulcer patients. The
      clinical implication of H. pylori eradication entails an improvement in clinical
      effectiveness and other dimensions of a patient's outcome and a significant
      reduction in the costs of duodenal ulcer treatment. The long-term total costs do
      not depend on the initial drug cost of an eradication regimen. Pursuing a high
      eradication rate of H. pylori is essential in improving the patient's outcome and
      the cost-effectiveness of treatment.

PMID- 9570242
TI  - Low dose of clarithromycin in triple therapy for the eradication of Helicobacter
      pylori: one or two weeks?
AB  - The aims of this pilot study were: (i) to compare the efficacy of low-dose
      clarithromycin (250 mg twice daily) for 1 or 2 weeks; and (ii) to evaluate
      possible therapeutic advantages in associating the low-dose clarithromycin with
      an anti-secretory agent or tripotassium dicitrate bismuthate (De Nol; Yamanouchi
      Pharm, Corugate Milano, Italy). A prospective, randomized, open trial was carried
      out on consecutive outpatients with dyspeptic symptoms and Helicobacter pylori
      infection. We enrolled 129 patients in one of the following schedules: (A) De Nol
      120 mg q.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2
      weeks; (B) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and
      metronidazole 250 mg q.i.d. for 2 weeks; or (C) omeprazole 20 mg b.i.d.,
      clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 1 week. Results
      were evaluated by Per Protocol (PP) and Intention-To-Treat analysis (ITT).
      Eradication rate was 100% after treatment A, 92.6% after treatment B and 86.5%
      after treatment C by PP and 83.3, 75.7, and 68.1%, respectively by ITT. Side
      effects were reported by 16 subjects: 26.6% in group A; 9.1% in group B; and 7.5%
      in group C; in two cases side effects led to the withdrawal of the treatment. In
      conclusion, 500 mg clarithromycin per day in association with omeprazole and
      metronidazole, for 1 week gave comparable results to the same schedule for a 2
      week period. The use of clarithromycin with bismuth and metronidazole produced a
      therapeutic gain compared with both of the anti-secretory schedules, although
      this was not statistically significant.

PMID- 9570243
TI  - Augmented levels of gastric mucosal leucocyte activation by infection with cagA
      gene-positive Helicobacter pylori.
AB  - The possession of the cytotoxin-associated gene (cagA) of Helicobacter pylori is
      thought to be highly associated with peptic ulcer disease. However, the
      pathogenic role of cagA is still unknown. We have emphasized the importance of
      the interrelationship between H. pylori-derived ammonia and oxygen radicals from
      infiltrated leucocytes. The aim of the present study was to explore the
      relationship between oxygen radical production and H. pylori strain diversity
      based on cagA possession. An endoscopic examination and gastric mucosal biopsy
      were performed in 30 H. pylori-infected patients with gastric ulcer.
      Myeloperoxidase (MPO) content and the luminol-dependent chemiluminescence value
      in the biopsied gastric specimens were measured as an index for leucocyte
      infiltration and oxygen radical production. From the precipitates of cultured
      bacterial isolates of biopsied specimens, bacterial DNA was purified and analysed
      by polymerase chain reaction to characterize the possession of cagA. While all
      patients had ureC-positive strains, 22 had cagA-positive and eight had cagA
      negative strains. In patients with cagA-positive strains, MPO contents as well as
      chemiluminescence values in the gastric corpus were significantly higher than
      those in patients with cagA-negative strains. Gastric mucosal leucocyte
      recruitment and activation are suggested to be enhanced by cagA gene-positive H.
      pylori infection.

PMID- 9570244
TI  - A prospective randomized study of amoxycillin and omeprazole with and without
      metronidazole in the eradication treatment of Helicobacter pylori.
AB  - A combination of amoxycillin and omeprazole is often used to treat Helicobacter
      pylori infection. A three-drug regimen comprising metronidazole, amoxycillin and
      omeprazole has been proposed as an alternative therapy. In a prospective,
      randomized, comparative study, we evaluated these two regimens with respect to
      safety and efficacy in patients with H. pylori infection. Sixty patients with
      peptic ulcer (gastric, 32 patients; duodenal, 28 patients) who had a history of
      ulcer recurrence were randomly assigned to dual therapy with amoxycillin (500 mg
      three times daily for 2 weeks) and omeprazole (20 mg once daily for 8 weeks) or
      to triple therapy with metronidazole (500 mg twice daily for 2 weeks) plus
      amoxycillin and omeprazole, given in the same dosages as dual therapy. Forty
      eight patients completed the protocol; treatment was discontinued because of side
      effects in nine patients, and three patients dropped out of the study. On the
      basis of all patients treated, the rate of H. pylori eradication was
      significantly higher for triple therapy 20/23 cases, 87.0%; 95% confidence
      interval (CI), 0.664-0.972) than for dual therapy 13/25, 52.0%; 0.313-0.722; P <
      0.05). On an intention-to-treat basis, the difference between the groups in the
      rate of H. pylori eradication was marginally significant (P = 0.06 [0.028
      0.512]). Side effects were reported by five patients receiving triple therapy
      (skin rash, one; nausea, two; headache, one; abdominal pain, one), and four
      patients receiving dual therapy (skin rash, two; abdominal pain, one; diarrhoea,
      one). All side effects resolved spontaneously after termination of treatment.
      There was no significant difference in safety between the two regimens. Triple
      therapy with metronidazole, amoxycillin, and omeprazole was significantly more
      effective for the eradication of H. pylori than dual therapy with amoxycillin and
      omeprazole alone. The safety of these regimens was similar, and triple therapy
      was found to be clinically acceptable.

PMID- 9570246
TI  - Case report: Metachronous early gastric carcinoma in a reconstructed gastric tube
      after radical operation for oesophageal carcinoma.
AB  - The incidence of double cancer has increased as a result of the significant
      advances in both diagnostic procedures and anti-cancer therapy, and as the
      outcome of oesophageal squamous cell carcinoma (ESCC) has improved, the number of
      cases of double cancer of the oesophagus and stomach has also increased. Two
      patients with metachronous early gastric carcinoma in a reconstructed gastric
      tube were successfully treated after subtotal oesophagectomy for ESCC. These
      cases have shown that early diagnosis of second cancer is very important for
      curative therapy.

PMID- 9570245
TI  - Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and
      p16 genes in human gastric carcinoma: with respect to histological subtypes and
      stages.
AB  - Although the mechanism remains obscure, two histological subtypes of gastric
      carcinoma (GC), the diffuse and intestinal types, differ drastically in
      epidemiological, clinical, pathological and biological characteristics. We
      investigated whether the genetic alterations of several oncogenes and tumour
      suppressor genes could be correlated with the two histological subtypes. In 60
      patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was
      studied using immunohistochemical stains. Mutations of the p15 and p16 tumour
      suppressor genes were assessed by polymerase chain reaction, Southern blotting,
      and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21
      (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2
      oncoprotein was more common in the intestinal type (15/32, 46.9%) and the
      advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the
      early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more
      frequently found in the intestinal type (19/32, 59.4%) and the advanced stage
      (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15,
      20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six
      (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point
      mutations of p16 nor alterations of p15 were detected. The frequency of
      alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter
      pylori infection. No correlation of genetic changes between any two genes was
      observed. Our preliminary results indicate alterations in the p15 gene were not
      important in gastric tumorigenesis, while infrequent homozygous deletions in the
      p16 gene play a limited role in tumour progression of intestinal-type GC.
      Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the
      intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may
      function independently of each other in gastric carcinogenesis. The association
      between genetic alterations and histological subtypes supports the notion that a
      distinct pathogenesis may exist in different histological subtypes.

PMID- 9570247
TI  - Familial occurrence of congenital bile duct cysts.
AB  - Congenital bile duct cysts are now a well-documented anomaly of the biliary tree,
      and have become more common in Japan. Familial occurrence of congenital bile duct
      cysts, however, is extremely rare, with only six reported cases in the
      literature. We report a familial pattern of congenital bile duct cysts in a
      mother and her daughter. A 33-year-old female was admitted for evaluation of
      right upper quadrant abdominal pain and fever 6 days after an uneventful delivery
      of her second child. A computed tomography (CT) and ultrasound scan (US) revealed
      an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then
      performed, and a cholangiogram revealed a Scholtz type B choledochocele without
      an anomalous connection of the pancreaticobiliary ducts. Endoscopic US
      demonstrated that the choledochocele was associated with a stone in the cyst. A
      pylorus-preserving pancreatoduodenal resection was performed, and a histological
      study revealed that the choledochocele was lined by biliary mucosa without
      evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT
      revealed a congenital bile duct cyst. An operation was performed and the
      intraoperative cholangiogram showed an Alonso-Lej type I congenital bile duct
      cyst with an anomalous connection of the pancreaticobiliary ducts. Whether
      congenital bile duct cysts are hereditary remains to be elucidated.

PMID- 9570248
TI  - Dieulafoy's disease treated by endoscopic haemostatic clipping.
AB  - Dieulafoy's disease is an uncommon cause of upper gastrointestinal haemorrhage.
      We report three patients with Dieulafoy's disease treated with the endoscopic
      haemostatic clip application. There was no recurrent bleeding from the upper
      gastrointestinal tract after application of the clips in all three patients. Two
      patients survived while the third succumbed to renal failure after hypovolaemic
      shock. We conclude that endoscopic haemostatic clip may have a role in the
      treatment of Dieulafoy's disease.

PMID- 9570249
TI  - Images in gastroenterology. Foreign bodies in the oesophagus.

PMID- 9570250
TI  - Liver metabolism of porphyrins and haem.
AB  - The liver is an active site for the biosynthesis of haem and
      porphyrinogens/porphyrins, which are intermediates of the haem biosynthetic
      pathway, because haem is required for functional activity of the cytochrome P 450
      system and other critical hepatic haemoproteins. The production of hepatic haem
      is regulated primarily through the activity of aminolaevulinic acid synthase
      which is the first and normally rate-limiting enzyme of the pathway. This is, in
      turn, controlled by a putative regulatory haem pool. Hepatic haem can be repleted
      by the intravenous administration of haem, which is the basis for haem therapy in
      patients with acute porphyric attacks. The liver catabolizes haem to bilirubin
      through microsomal haem oxygenase activity and excretes haem into bile along with
      porphyrins. Biliary excretion of porphyrins increases significantly in patients
      with some types of porphyria. In protoporphyria this may cause liver damage as a
      result of protoporphyrin toxicity. The delineation of the pathway for
      protoporphyrin excretion into bile should facilitate therapy in protoporphyria by
      identifying ways in which protoporphyrin excretion can be enhanced.

PMID- 9570251
TI  - The influence of iron on chronic hepatitis C.
AB  - It has recently been suggested that the hepatic iron concentration can be used to
      predict the response to interferon in patients with chronic hepatitis C. An
      hepatic iron concentration greater than 1100 microg/g appears to identify a group
      of patients that are unlikely to respond to alpha-interferon. It is not known
      whether this relationship can be explained by associated variables such as age,
      gender or disease severity or whether the hepatic iron concentration itself
      influences the response to interferon. Furthermore, the hepatic iron
      concentration is of no value in discriminating responders from non-responders in
      patients with hepatic iron concentrations less than 1100 microg/g. The
      possibility of improving response rates to interferon by pretreatment venesection
      needs to be explored but currently only limited data are available. Venesection
      results in a significant fall in the serum transaminases but the preliminary
      results regarding the efficacy of subsequent interferon therapy are unclear.
      Until the results of prospective controlled trials are available it is concluded
      that the available evidence does not support venesection before interferon
      therapy for chronic hepatitis C.

PMID- 9570252
TI  - Review article: oesophageal mucosal resistance.
AB  - The human oesophagus is lined by a moist, partially keratinized, stratified
      squamous epithelium, one important property of which is to serve as a barrier
      between the outside (luminal) world and the internal world of the organism. This
      phenomenon in clinical parlance is known as 'oesophageal mucosal resistance'.
      This article details the structure and functions of the oesophageal mucosa that
      contribute to its defence against injury upon exposure to refluxed gastric acid.

PMID- 9570253
TI  - Review article: glycyrrhizin as a potential treatment for chronic hepatitis C.
AB  - Chronic hepatitis C is a slowly progressive liver disease that may evolve into
      cirrhosis with its potential complications of liver failure or hepatocellular
      carcinoma. Current therapy with alpha-interferon is directed at viral clearance,
      but sustained response is only achieved in 20-40% of patients without cirrhosis,
      and less than 20% in patients with cirrhosis who have the greatest need for
      therapy. Treatment for those who do not respond to anti-viral therapy is highly
      desirable. In Japan glycyrrhizin has been used for more than 20 years as
      treatment for chronic hepatitis. In randomized controlled trials, glycyrrhizin
      induced a significant reduction of serum aminotransferases and an improvement in
      liver histology compared to placebo. Recently, these short-term effects have been
      amplified by a well-conducted retrospective study suggesting that long-term usage
      of glycyrrhizin prevents development of hepatocellular carcinoma in chronic
      hepatitis C. The mechanism by which glycyrrhizin improves liver biochemistry and
      histology are undefined. Metabolism, pharmacokinetics, side-effects, and anti
      viral and hepatoprotective effects of glycyrrhizin are discussed.

PMID- 9570254
TI  - Antibiotic prophylaxis for ERCP: a comparison of oral ciprofloxacin with
      intravenous cephazolin in the prophylaxis of high-risk patients.
AB  - BACKGROUND: Cholangitis and septicaemia are serious complications of endoscopic
      retrograde cholangiopancreatography (ERCP). They occur mainly following
      therapeutic ERCP in the setting of an obstructed biliary system. The optimum
      prophylactic antibiotic regimen in such patients is not yet defined but usually
      depends on intravenous agents. AIM: To compare the efficacy of oral ciprofloxacin
      with intravenous cephazolin. METHODS: One hundred and fifty patients at high risk
      from septic complications were randomized prospectively to either oral
      ciprofloxacin (750 mg b.d.) or intravenous cephazolin (1 g b.d.), commenced at
      least 90 min prior to the ERCP and continued for 3 days. Bacteriological cultures
      were taken from bile during the procedure and from blood both immediately and at
      24 h post-procedure. RESULTS: There were no significant differences between the
      two treatment groups in the pre-ERCP clinical or radiological findings or in the
      types of procedure performed. One patient did not undergo an ERCP and was
      excluded from the final analysis. Of the 77 patients in the ciprofloxacin group
      there were no positive blood cultures and one positive culture from a nasobiliary
      drain. Two out of the 72 cephazolin patients had positive blood cultures
      immediately post-ERCP; one of these two patients and one other cephazolin patient
      had positive bile cultures. There were no cases of cholangitis or septicaemia in
      the ciprofloxacin group and three cases in the cephazolin group. One patient from
      each treatment group died within the 7-day study. Adverse drug reactions were
      minimal and none of the different clinical outcomes in the two groups reached
      statistical significance. CONCLUSION: Oral ciprofloxacin is a cost-effective
      prophylactic agent for high-risk ERCP.

PMID- 9570255
TI  - The effect of rectally administered steroids on bone turnover: a comparative
      study.
AB  - BACKGROUND: Oral glucocorticoids contribute significantly to the risk of
      osteoporosis in patients with inflammatory bowel disease. Less well established
      are the effects of rectally administered steroids on bone metabolism. AIM: To
      investigate the effects of two widely used rectal foam preparations (prednisolone
      metasulphobenzoate and hydrocortisone acetate) on biochemical markers of bone
      turnover. METHODS: Twenty-four patients with active inflammatory bowel disease
      randomly received a standard course of either prednisolone metasulphobenzoate or
      hydrocortisone acetate for 2 weeks. Biochemical markers of bone turnover were
      measured before, during and after treatment. Bone formation markers measured were
      serum osteocalcin (BGP) and bone-specific alkaline phosphatase (BALP). Urinary
      deoxypyridinoline (DPD) was measured to assess bone resorption. RESULTS: Disease
      activity scores improved during treatment (difference in mean Powell-Tuck score =
      3.4, 95% CI: 2.0-4.8, P < 0.0001) and were similar in both hydrocortisone and
      prednisolone-treated groups. There was no significant reduction in BALP or BGP
      during treatment with either steroid preparation, and urinary DPD did not change
      significantly during treatment. CONCLUSIONS: During a 2-week course of rectal
      hydrocortisone acetate or prednisolone metasulphobenzoate, there was no
      significant change in biochemical markers of bone formation or resorption. These
      results suggest that pharmacological doses of rectal steroid foam preparations do
      not significantly impair bone turnover in patients with inflammatory bowel
      disease.

PMID- 9570256
TI  - Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid
      induced colitis in the rat.
AB  - BACKGROUND: We investigated the effects of benzalkonium chloride (BAC) on
      trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: TNBS was
      administered intrarectally before and/or after BAC treatment. In the first study,
      the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the
      second study, animals were treated with BAC before, after or before and after
      TNBS, and were examined 7 days later. The severity of colitis was assessed by
      macroscopic and histological scoring of the colonic damage and by determination
      of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells
      were examined by immunohistochemistry. RESULTS: When BAC was instilled into the
      colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological
      features of the colon were similar to that of controls (TNBS alone). In contrast,
      MPO activity was significantly reduced in all three groups post-treated with BAC.
      In the groups examined 7 days after TNBS treatment, rats post-treated with BAC
      exhibited increased weight gain and significantly reduced macroscopic damage and
      MPO activity compared to the TNBS control group. Rats pre-treated with BAC
      exhibited less macroscopic damage of the colon than rats receiving only TNBS, but
      histological damage, MPO and weight gain were unchanged from TNBS controls.
      Immunohistochemistry revealed that BAC pre-treatment increased the numbers of
      macrophages and T cells in the colon. After TNBS treatment, macrophage
      accumulation was evident in the colon, but T cells were scarce. However, these
      cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that
      had been pre-treated with BAC. CONCLUSIONS: Treatment with BAC, particularly
      after induction of colitis, produces a significant reduction in the severity of
      tissue injury and inflammation through mechanisms that are not fully understood.

PMID- 9570258
TI  - Meta-analysis of somatostatin, octreotide and gabexate mesilate in the therapy of
      acute pancreatitis.
AB  - BACKGROUND: Autodigestion of the pancreas, secondary to the activation of
      digestive enzymes, is the pathogenetic mechanism of acute pancreatitis (AP). AIM:
      Clinical trials in which somatostatin (SS), octreotide (OCT) and gabexate
      mesilate (FOY) were used to treat patients with AP, were submitted to a meta
      analytical evaluation. Five end-points were evaluated: early and overall
      mortality, patients with complications, complication rate, and patients who
      needed surgery. RESULTS: In mild AP, no agent proved of value. In severe AP, both
      SS and OCT were beneficial in improving the overall mortality: the odds ratios
      (OR) were, respectively, 0.36 (95% CI: 0.20-0.64, P = 0.001) and 0.57 (95% CI:
      0.35-0.88, P = 0.006). FOY had no effect on either early or overall mortality,
      but was effective in improving complication rate (OR = 0.70, 95% CI: 0.56-0.88, P
      = 0.02), number of patients with complications (OR = 0.61, 95% CI: 0.41-0.91, P =
      0.01), and number of cases submitted to surgery (OR = 0.60, 95% CI: 0.39-0.92, P
      = 0.01). SS and OCT had no effect on these latter outcomes. CONCLUSIONS:
      Antisecretory agents, such as SS and OCT, are able to reduce mortality without
      affecting complications, whereas antiproteases, such as FOY, have no effect on
      mortality but do reduce complications. A trial exploring the efficacy of
      combining antisecretory agents with antiproteases would be of great benefit in
      patients with severe AP.

PMID- 9570257
TI  - The effect of heparin on trinitrobenzene sulphonic acid-induced colitis in the
      rat.
AB  - BACKGROUND: Reduced blood coagulability seems to protect against inflammatory
      bowel disease; pilot studies using heparin in patients with inflammatory bowel
      disease have reported positive results. AIM: To evaluate the effects of heparin
      treatment on microangiographic and on inflammatory parameters in experimental
      colitis, induced by trinitrobenzene sulphonic acid (TNBS)-ethanol. METHODS: Four
      groups of rats: (i) controls (saline enema), TNBS-induced colitis with (ii) sham
      treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv)
      heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days
      after colitis induction. Partial thromboplastin time, colonic wet weight,
      macroscopic damage score and mucosal myeloperoxidase (MPO) activity were
      determined at day 4. RESULTS: TNBS-induced colitis caused a reduction in visible
      bowel wall vessels, which was prevented by heparin (P < 0.05) but not by
      steroids. The macroscopic damage scores and colon wet weights were similar in all
      colitis groups. Compared to untreated colitis the MPO activity in heparin-treated
      animals was of borderline significance. CONCLUSIONS: Heparin treatment improved
      microangiographic features and reduced inflammation to a certain degree. Steroids
      delayed development of colon hypoperfusion, but were ineffective on MPO activity.
      It remains to be determined if the observed effects are due to the antithrombotic
      activity of heparin or to an anti-inflammatory action.

PMID- 9570259
TI  - Changes in Helicobacter pylori-induced gastritis in the antrum and corpus during
      12 months of treatment with omeprazole and lansoprazole in patients with gastro
      oesophageal reflux disease.
AB  - BACKGROUND: Several studies have shown that treatment with omeprazole leads to
      aggravation of Helicobacter pylori gastritis in the corpus. Whether this also
      applies to lansoprazole, and whether, in comparison with omeprazole, there are
      differences in therapy-induced gastritis parameter changes remains unclear.
      METHODS: In 111 patients infected with H. pylori and with gastro-oesophageal
      reflux disease we investigated the gastritis parameters in antral and corpus
      mucosa before and after 2, 6 and 12 months of treatment with 15 or 30 mg
      lansoprazole or 20 mg omeprazole/day. RESULTS: In all groups the different
      treatments had a similar effect: in both regions of the stomach, suppression or
      partial elimination of H. pylori was seen. However, improvement in the
      inflammation was observed only in the antrum, while in the corpus most gastritis
      parameters worsened significantly. There was no increase in intestinal metaplasia
      or atrophy. CONCLUSION: In common with omeprazole, lansoprazole aggravates the
      gastritis parameters in the corpus but improves them in the antrum. Treatment
      with proton pump inhibitors does not result in any increase in the incidence of
      atrophy/intestinal metaplasia. However, as gastritis predominating in the corpus
      seems to be associated with an elevated carcinogenic risk, consideration should
      be given to prophylactic H. pylori eradication therapy before initiating proton
      pump inhibitor treatment.

PMID- 9570260
TI  - The effects of low doses of ranitidine on intragastric acidity in healthy men.
AB  - BACKGROUND: H2-receptor antagonists are becoming widely available as over-the
      counter medications for the treatment of heartburn and excess gastric acidity.
      AIM: To determine the effects of single low doses of ranitidine on intragastric
      acidity. METHODS: Intragastric pH was measured for 9 h after lunch in five
      studies involving 24 healthy male volunteers. Antacid was given to all subjects
      on day 1. They then received single oral doses of a study drug 45 min after lunch
      on four separate occasions: placebo and either ranitidine 25 mg, 75 mg or 125 mg
      were given double-blind according to a predetermined randomization schedule.
      RESULTS: During both of the post-dosing time periods (0-5 h and 5-9 h) there were
      significant decreases in integrated intragastric acidity for each ranitidine dose
      compared with placebo (P < 0.0001). There was a significant linear relationship
      between dose and integrated intragastric acidity with a greater decrease in
      acidity with increasing ranitidine doses (P < 0.0001). Compared with placebo,
      time with pH > 3 was significantly greater for ranitidine 75 mg and 125 mg (P <
      0.001), but not ranitidine 25 mg. Results with the antacid were similar to
      placebo. CONCLUSIONS: Using low doses of ranitidine (25, 75 or 125 mg) there was
      a dose-related decrease in intragastric acidity for 9 h after dosing. A single
      dose of antacid did not decrease intragastric acidity significantly.

PMID- 9570261
TI  - The management of acid-related dyspepsia in general practice: a comparison of an
      omeprazole versus an antacid-alginate/ranitidine management strategy. Compete
      Research Group [corrected].
AB  - BACKGROUND: There is need for an evidence-based comparison of clinical management
      strategies to provide the rationale for selection of a particular therapeutic
      approach to treatment. Ideal dyspepsia treatment should quickly and conveniently
      alleviate patient symptoms whilst also minimizing the use of healthcare
      resources. AIM: To examine dyspepsia symptom relief over 16 weeks and compare an
      omeprazole clinical management strategy with a commonly used combination of
      antacid-alginate followed by H2-antagonist. METHODS: Seven hundred and twenty
      five patients participated in this randomized, open, parallel group comparison
      over 16 weeks. Patients were randomized to receive either an omeprazole treatment
      strategy (363) consisting of omeprazole 10 mg stepping up to 20 mg and 40 mg as
      required, or an antacid-alginate/ranitidine treatment strategy (362) consisting
      of antacid-alginate 10 mL q.d.s. stepping up to ranitidine 150 mg b.d. and 150 mg
      q.d.s. as required. RESULTS: A greater proportion of patients receiving the
      omeprazole clinical management strategy had achieved the stringent health target
      of complete symptom relief (61 vs. 40%, P < 0.0001) at 16 weeks. Forty-six per
      cent of omeprazole-treated patients were symptom free after the first 10 mg step
      compared to only 17% in the antacid-alginate treated group (P = 0.0001). Total
      relief of heartburn, the most common symptom at entry, was achieved by more
      patients in the omeprazole treatment group than the antacid-alginate/ranitidine
      treatment group, 62 vs. 36%, respectively, at 4 weeks, and 81 vs. 60% at 16 weeks
      (P = 0.0001). CONCLUSION: Treatment with the omeprazole clinical management
      strategy was superior to the antacid-alginate/ranitidine management strategy in
      providing relief of acid-related dyspepsia symptoms after 16 weeks. In addition,
      the omeprazole treatment strategy involved fewer GP consultations and thus
      minimized the use of other healthcare resources.

PMID- 9570262
TI  - Lansoprazole triple therapy for Helicobacter pylori--is 5 days enough?
AB  - BACKGROUND: Seven-day proton pump inhibitor triple therapy is currently the
      treatment of choice for Helicobacter pylori infection. It is unclear whether
      triple therapy for less than 7 days might preserve efficacy while at the same
      time improving patient acceptability and compliance. AIM: To evaluate the
      Helicobactericidal efficacy, ulcer healing capacity and patient acceptability of
      a 5-day lansoprazole-based triple therapy regimen. METHODS: Sixty-nine
      consecutive patients with H. pylori-positive peptic ulcer received lansoprazole
      30 mg twice daily in combination with metronidazole 400 mg twice daily and
      clarithromycin 250 mg twice daily for 5 days. Ulcer healing medication was not
      continued after the 5-day regimen. H. pylori status was assessed before and at
      least 4 weeks after therapy by rapid urease test and histology. Adverse events
      and compliance were assessed by direct questioning. RESULTS: All 69 patients
      attended for repeat endoscopy and 63 were H. pylori-negative after therapy giving
      a cure rate of 91%, (95%, Cl: 85-98%). Of the 59 patients with active ulcers, 58
      were healed at repeat endoscopy giving an ulcer healing rate of 98% (95% Cl: 92
      100%). All patients fully complied with therapy and mild adverse events, mainly
      gastrointestinal, were reported by 11 patients (16%). CONCLUSIONS: Five-day
      lansoprazole triple therapy is an effective regimen for H. pylori infection which
      combines a high cure rate and ulcer healing efficacy with the advantages of
      excellent patient acceptability and compliance.

PMID- 9570263
TI  - Bismuth-containing single-antibiotic 1-week triple therapy for Helicobacter
      pylori eradication.
AB  - BACKGROUND: Although bismuth was both the first drug shown to alter the natural
      history of peptic ulcer disease and also a constituent of the first very
      effective eradication regimens, it has been excluded from the newer regimens,
      despite its safety and low cost, in favour of two antibiotics. AIM: To asses a
      novel 1-week regimen consisting of bismuth, clarithromycin and a proton pump
      inhibitor in routine clinical practice. METHODS: One hundred and three
      consecutive patients with peptic ulcer disease and antral biopsies containing
      Helicobacter pylori were given a 7-day course of treatment with bismuth
      (tripotassium dicitrato bismuthate chelate) 120 mg q.d.s., clarithromycin 500 mg
      t.d.s. and lansoprazole 30 mg o.d. Completeness of eradication was assessed by a
      l3C-urea breath test, in all except three patients, at least 4 months later.
      RESULTS: Of the 100 patients who were assessed in this open treatment study 84
      (84%; 95% CI: 77-91%) had a negative breath test. Minor side-effects were
      reported by 14% and more troublesome side-effects (nausea, vomiting, diarrhoea,
      hallucinations, nasty taste and body pains) were reported by 10%. CONCLUSIONS: A
      1-week course of triple therapy including bismuth, clarithromycin and a proton
      pump inhibitor is effective in routine clinical practice and is well tolerated.

PMID- 9570264
TI  - The role of osmolality in the absorption of a nutrient solution.
AB  - BACKGROUND: Loss of water during enteral nutrition following massive intestinal
      resection may be severe. Low osmolality of oral rehydration solutions has
      recently been shown to mediate an increase in water absorption. AIM: To evaluate
      the effect of osmolality of a nutrient solution on the intraluminal
      duodenojejunal water flow, and the net absorption rates of total nitrogen and
      carbohydrate. METHODS: Eight healthy volunteers with a mean age of 27 (range 25
      29) years participated in the study. Enteral nutrition (17% protein, 59%
      carbohydrate, 24% lipid plus 5 g/L PEG 4000) was infused (5 mL/min 2.64 kcal/min)
      into the descending duodenum either as a hypotonic (160 mOsmol/kg) or as an
      isotonic solution in a random order. Intestinal samples were aspirated 20 and 45
      cm distally to the infusion point. RESULTS: Intraluminal water flow rates were
      significantly lower with the hypotonic solution than with the isotonic solution,
      both in the duodenum (4.9 +/- 0.3 vs. 6.7 +/- 0.5 mL/min; P < 0.02) and the upper
      jejunum (3.0 +/- 0.1 vs. 3.9 +/- 0.2 mL/min; P < 0.005). The net absorption rates
      of total nitrogen and carbohydrate were similar with both solutions. CONCLUSION:
      Low osmolality of a nutrient solution decreases intraluminal water flow rates in
      the upper intestine without affecting the absorption rates of total nitrogen and
      carbohydrate. Compared with an isotonic solution, the use of a hypotonic solution
      might lower the water loss in patients with extensive short bowel intestinal
      resection.

PMID- 9570265
TI  - Secretion of vascular endothelial growth factor/vascular permeability factor from
      human luteinized granulosa cells is human chorionic gonadotrophin dependent.
AB  - Vascularization is a prominent event during corpus luteum formation, providing
      low density lipoproteins for steroid biosynthesis and enabling transport of
      secreted steroids. The process of vascularization is controlled by specific
      regulators. Vascular endothelial growth factor (VEGF), otherwise named vascular
      permeability factor (VPF), induces endothelial cell proliferation as well as
      angiogenesis in vivo and increases capillary permeability. Here we report the
      expression of VEGF/VPF mRNA by cultured human luteinized granulosa cells (GC) for
      at least 10 days. Without HCG VEGF/VPF expression declined after day 4 and by day
      10 was reduced to approximately 30% of the value at day 4. However, after culture
      in the presence of 1 U/ml human chorionic gonadotrophin (HCG), expression of
      VEGF/VPF mRNA by GC was four times greater than control experiments by day 10,
      and increased 100% from day 4 to day 10. Simultaneously, HCG supplementation
      increased VEGF/VPF secretion by GC. Medium VEGF/VPF on day 3 was 13 pM without
      and 11 pM with HCG. Medium VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with
      HCG. These results suggest that vascularization of the corpus luteum is induced
      by HCG-mediated effects of VEGF/VPF.

PMID- 9570266
TI  - Ovarian transforming growth factor-beta (TGF-beta) receptors: in-vitro effects of
      follicle stimulating hormone, epidermal growth factor and TGF-beta on receptor
      expression in human preantral follicles.
AB  - The expression patterns of transforming growth factor (TGF)-beta receptor type I
      (TbetaRI) and -II (TbetaRII) in pre- and post-menopausal human ovaries, and the
      in-vitro effects of follicle stimulating hormone (FSH), epidermal growth factor
      (EGF) and transforming growth factor-beta1 (TGF-beta1) on receptor expression in
      preantral follicles were evaluated using immunohistochemistry and immunoblotting.
      Both types of receptor were present in granulosa, theca and interstitial cells;
      however, more mural than antral granulosa cells were TbetaRII positive. Overall,
      more cells expressed TbetaRI than TbetaRII. TbetaRI and TbetaRII expressions were
      detected in the membrane as well as in the soluble fractions. However, marked
      increases in TbetaRII and TbetaRI expression in the soluble fraction and
      corresponding decreases in the membrane fraction were noted in the post
      menopausal ovary. Preantral follicles in class 1 and 2 responded in vitro to FSH
      and EGF with increased growth and a corresponding increase in TbetaRII expression
      in granulosa cells; however, TGF-beta did not influence follicular growth or
      receptor expression. There was no apparent change in follicular TbetaRI
      immunoreactivity regardless of test factors or follicular growth status. These
      results suggest that TbetaRI and TbetaRII are expressed differentially in human
      ovarian cells, particularly in the granulosa cells. The shift in TbetaR-I and -II
      from transmembrane to soluble fraction after menopause indicates that the
      endocrine milieu provided by the granulosa cells positively influences receptor
      induction in the membrane and, hence, the biological action of TGF-beta. FSH- and
      EGF-induced preantral follicular development is associated with a selective
      induction of TbetaRII and may indicate a mechanism whereby gonadotrophins and
      growth factor(s) regulate preantral folliculogenesis.

PMID- 9570267
TI  - Alternative splicing of exons in the alpha1 subunit of the rat testis L-type
      voltage-dependent calcium channel generates germ line-specific dihydropyridine
      binding sites.
AB  - Cell-specific isoforms of the alpha1 subunit of the L-type voltage-dependent
      calcium channel (VDCC) have unique pharmacological reactivities. Prior sequence
      analysis of nucleotide bases 3908-6077 of the VDCC alpha1 subunit expressed in
      rat testis differed from cardiac sequences only in a 84 base pair region
      corresponding to exons 31/32 encoding a putative dihydropyridine binding region.
      We now report that sequence analysis of bases 3048-3936 identifies a second
      difference between the rat testis and rat cardiac alpha1 sequence in a 60 base
      pair region corresponding to exons 21/22 and encoding another putative
      dihydropyridine binding site. Variable VDCC exons 21/22 and 31/32 and their
      linking introns were sequenced using genomic DNA from rat lung as template,
      providing evidence that the rat testis and cardiac alpha1 isoforms are products
      of the same gene. Reverse transcription in-situ polymerase chain reaction (PCR)
      with frozen sections of rat testis was carried out with primers identifying the
      testis-specific exon 32 of the VDCC alpha1 subunit. PCR products were confined to
      seminiferous tubules and were associated with the germ cell lineage from Type A
      spermatogonia to mature spermatozoa. Close coupling of testis alpha1 VDCC gene
      transcription and translation was established by in-situ immunolabelling of
      serial frozen sections with a monoclonal antibody (IIF7) directed against
      epitopes on rabbit skeletal muscle L-type VDCC alpha1. Western blot analysis of
      rat proteins extracted from heart, skeletal muscle, testis and spermatozoa which
      were reactive with the IIF7 antibody detected primarily 175-220 kDa proteins in
      the size range of VDCC. These data unequivocally demonstrate that an L-type VDCC
      is expressed in rat testis and that VDCC isoforms from rat testis and heart
      differ in deduced amino acid composition in and around potential binding sites
      for calcium channel blocking drugs such as the dihydropyridines.

PMID- 9570268
TI  - The proliferation of spermatogonia in normal and pathological human seminiferous
      epithelium: an immunohistochemical study using monoclonal antibodies against Ki
      67 protein and proliferating cell nuclear antigen.
AB  - The quantitative distribution pattern of Ki-67 protein and proliferating cell
      nuclear antigen (PCNA) immunoreactivity was studied in human testis biopsies. In
      normal seminiferous epithelium Ki-67 is expressed in nuclei of spermatogonia,
      while PCNA additionally occurs in nuclei of primary spermatocytes. The staining
      pattern of spermatogonia is as follows (Ki-67-positive/PCNA-positive): 26.6 +/-
      12.4%/46.3 +/- 9.5%. No stage-dependent differences were found. Biopsies with
      mixed atrophy (score < or =7) showed a significant (P < 0.05) decrease of
      immunopositive spermatogonia to 19.9 +/- 3.0%/31.4 +/- 5.7% (score 1) with
      minimal variation between different samples (score 7 to 1). Associated with
      defined histological defects such as hypospermatogenesis (hyp), spermatogenic
      arrest at the level of spermatids (sda), spermatocytes (sca) or spermatogonia
      (sga), however, there was a significant (P < 0.05) decrease of Ki-67 staining in
      tubules showing hyp (28.6 +/- 8.8%), sda (25.6 +/- 9.3%), sca (23.7 +/- 9.3%) and
      sga (16.2 +/- 6.0%) and of PCNA staining in sca (32.2 +/- 11.8%) and sga (20.0 +/
      9.5%), respectively. The decrease of immunoreactive spermatogonia did not
      correspond to elevation of follicle stimulating hormone (FSH). These data
      demonstrate that the low spermatogenic efficiency in infertile men is not only
      due to postmeiotic events, but also to a decrease in the meiotic activity of
      spermatogonia, and is not related to serum FSH.

PMID- 9570269
TI  - Expression of extracellular superoxide dismutase in the human male reproductive
      tract, detected using antisera raised against a recombinant protein.
AB  - Mammalian spermatozoa are particularly susceptible to the deleterious effects of
      reactive oxygen species and lipid peroxidation, which ultimately lead to impaired
      fertility. A number of enzymes are present in the male reproductive tract which
      may play a role in preventing oxidative damage; in particular, the epididymis is
      the site of synthesis and secretion of large amounts of extracellular superoxide
      dismutase (eSOD). In order to study the distribution of eSOD in the male
      reproductive tract, and distinguish it from other related superoxide dismutase
      isoenzymes (e.g. cytosolic SOD), polyclonal antisera have been raised against a
      recombinant human eSOD fusion protein, expressed in bacterial cells. This protein
      was expressed from a synthetic gene fragment, using preferred Escherichia coli
      codons, designed to overcome the problems associated with the high
      guanine+cytosine content of the natural human eSOD transcript. Using this
      antiserum, eSOD can be readily detected in a range of human reproductive tissues
      as well as in human seminal plasma. However, the presence of similar levels of
      eSOD in the seminal plasma of vasectomized men (probably of prostatic origin)
      precludes its use as a simple diagnostic indicator of eSOD activity levels in the
      epididymis.

PMID- 9570270
TI  - Evaluation of stimulus-induced acrosome reaction by two-colour flow cytometric
      analysis.
AB  - Acrosome status in human spermatozoa from 20 normozoospermic men was evaluated by
      flow cytometry following the induction of the acrosome reaction with the
      ionophore A23187. Dual fluorescence staining of methanol fixed spermatozoa
      incubated with and without (control) the ionophore A23187 was performed with
      probes which targeted the outer acrosomal membrane (OAM) (rhodamine-labelled
      Arachis hypogaea agglutinin) or constituents of the acrosomal vesicle
      (fluorescein-labelled Pisum sativum agglutinin). Flow cytometry analysis revealed
      two major subpopulations of cells: acrosome-intact and acrosome-reacted
      spermatozoa after induction of the acrosome reaction. The intensity of green and
      red fluorescence in acrosome-reacted spermatozoa was significantly lower than
      that of the acrosome-intact control spermatozoa (P < 0.0001). The intensity of
      green fluorescence in the acrosome-intact subpopulation of spermatozoa was
      significantly higher than that of the control population (P < 0.002). Exposure of
      spermatozoa to the ionophore A23187 resulted in reliable enhancement of the
      number of spermatozoa with very high intensity of green and/or red fluorescence
      compared with the control (P < 0.03). An inverse correlation between the number
      of acrosome-reacted spermatozoa and spermatozoa with a very high intensity of
      green and/or red fluorescence was demonstrated (r = -0.631, P < 0.01). This
      method provides an objective and efficient procedure for quantitative estimation
      of the acrosomal status of human spermatozoa.

PMID- 9570271
TI  - Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in
      human spermatozoa.
AB  - Mitogen-activated protein kinases (MAPK), also known as extracellular signal
      regulated kinases (ERKs) are cytoplasmic and nuclear serine/threonine kinases
      involved in signal transduction of several extracellular effectors. Recently, we
      have demonstrated that ERKs are present in spermatozoa and are involved in the
      regulation of the process of capacitation. We report here the effect of
      progesterone, a well-known inducer of the acrosome reaction in mammalian
      spermatozoa, on the immunolocalization, phosphorylation and activity of ERKs in
      capacitated human spermatozoa. We demonstrated that short-term incubation of
      spermatozoa with progesterone induces phosphorylation and activation of ERKs,
      resulting in redistribution of the proteins from the post-acrosomal region to the
      equatorial segment within the sperm head. To investigate the role of ERKs on the
      biological effects of progesterone, we used the MAPK cascade inhibitor PD098059,
      which strongly inhibited progesterone-induced activation of ERK-2. This compound
      did not inhibit progesterone-induced acrosome reaction, although it prevented
      redistribution of the enzyme to the equatorial region of the sperm head. These
      results suggest that the two processes, although temporally related, are
      independent. In conclusion, we provide new insight into the signal transduction
      pathways involved in the non-genomic action of progesterone in spermatozoa and
      suggest a possible involvement of ERKs in the process of fertilization.

PMID- 9570272
TI  - Progesterone-stimulated intracellular calcium increase in human spermatozoa is
      protein kinase C-independent.
AB  - Indirect studies suggested that protein kinase C (PKC) has a role in sperm
      motility and the acrosome reaction. Physiological inducers of the sperm acrosome
      reaction include progesterone, which can increase intracellular calcium
      ([Ca2+]i), tyrosine phosphorylation of proteins and chloride efflux in human
      spermatozoa. PKC may be involved in progesterone-stimulated acrosome reaction,
      although controversial results have been obtained concerning the effect of PKC
      inhibition on progesterone-stimulated [Ca2+]i increase. In the present study, we
      investigated the direct effect of progesterone on the activity of PKC, as well as
      the effect of a panel of PKC inhibitors on progesterone-stimulated [Ca2+]i
      increase and tyrosine phosphorylation of proteins. We found that progesterone
      stimulates sperm PKC activity and that PKC inhibition with staurosporine and
      bisindolylmaleimide partially reversed the effect of progesterone on acrosome
      reaction, indicating an involvement of the enzyme in the effect of the steroid.
      We next evaluated the effect of three different PKC inhibitors (sangivamycin,
      staurosporine and bisindolylmaleimide) on progesterone-stimulated [Ca2+]i
      increase. Neither short-term (15 min) nor long-term (90 min) preincubation with
      any of the three compounds had a substantial effect on the stimulatory effect of
      progesterone on sperm [Ca2+]i. Nor was responsiveness to progesterone affected by
      either short-term (determining activation of PKC) or long-term (determining down
      regulation of PKC) incubation with the tumour promoter phorbol myristate acetate
      (PMA), a known non-physiological stimulator of PKC. These results indicate that
      progesterone-stimulated calcium influx is independent of PKC activation. In
      addition, we found that preincubation with PKC inhibitors had a stimulatory
      effect per se on tyrosine phosphorylation of sperm proteins. When compared with
      the appropriate control, the effect of progesterone on tyrosine phosphorylation
      was slightly (but not significantly) reduced by the inhibitors, sangivamycin,
      staurosporine and bisindolylmaleimide, but was significantly inhibited by
      calphostin C. These results do not permit a final conclusion on the involvement
      of PKC in progesterone-stimulated tyrosine phosphorylation of sperm proteins.
      However, the lack of effect of PMA on tyrosine phosphorylation indicates that PKC
      stimulation is not sufficient to induce this effect. In conclusion, our results
      indicate that PKC plays a role in progesterone-induced acrosome reaction and that
      progesterone-stimulated PKC activation is downstream to stimulation of calcium
      influx by the steroid.

PMID- 9570273
TI  - Ooplasmic transfer in mature human oocytes.
AB  - Ooplasmic transplantation aimed at restoring normal growth in developmentally
      compromised oocytes and embryos was evaluated in seven couples (eight cycles)
      with multiple implantation failures. Two approaches were investigated to transfer
      ooplasm from donor eggs at metaphase II (MII) stage into patient MII eggs: (i)
      electrofusion of a ooplasmic donor fragment into each patient egg (three cycles),
      and (ii) direct injection of a small amount of ooplasm from a donor egg into each
      patient egg (five cycles). Some donor eggs were used multiple times. Donor eggs
      were divided into two groups, one being used for ooplasmic extraction and the
      other one for egg donation. Cleaved embryos resulting from the latter were
      cryopreserved, where numbers and satisfactory development permitted. A second
      control group consisted of embryos derived from patient eggs after
      intracytoplasmic sperm injection without ooplasmic transfer. This was performed
      when sufficient number of eggs were available (n = 5). Donor eggs (n = 40) were
      evaluated cytogenetically after micromanipulation in order to confirm the
      presence of chromosomes. One egg was anuclear and the recipient embryos were not
      transferred. Normal fertilization was significantly higher after injection of
      ooplasm (63%) in comparison with fusion (23%). Pronuclear anomalies appeared
      enhanced after fusion with ooplasts. Embryo morphology was not improved in the
      three cycles with electrofusion and patients did not become pregnant. An
      improvement in embryo morphology was noted in two patients after injection of
      ooplasm and both became pregnant, but one miscarried. A third pregnancy was
      established in the repeat patient, without obvious embryo improvement. One baby
      was born and the third pregnancy is ongoing with a normal karyotype. Two other
      patients with male factor infertility had poor embryos after ooplasmic injection,
      but the donor embryo controls were also poor. The patients did not become
      pregnant and had no donor embryos frozen. Ooplasmic transfer at the MII stage may
      be promising in patients with compromised embryos; however, evaluation of
      ooplasmic anomalies and optimization of techniques will require further
      investigation prior to widescale application.

PMID- 9570274
TI  - Antioxidant therapy counteracts the disturbing effects of diamide and maternal
      ageing on meiotic division and chromosomal segregation in mouse oocytes.
AB  - This study aims (i) to ascertain whether oxidative-stress-induced disturbances in
      chromosomal distribution in the metaphase-II spindle of mouse oocytes can be
      counteracted by supplementing culture medium with antioxidants; and (ii) to
      determine whether supplemental intake of antioxidants neutralizes the disturbing
      effects of maternal ageing on segregation of chromosomes during the first meiotic
      division and distribution of chromosomes in the metaphase-II spindle. (i):
      Germinal vesicle oocytes from unstimulated 10-12 week old mice were matured in
      vitro in the presence or absence of diamide and/or dithiothreitol. Metaphase-II
      oocytes were fixed and stained with 4',6-diamidino-2-phenylindole (DAPI) to
      detect abnormalities in chromosomal distribution. The percentage of oocytes
      arrested in metaphase I (12.9% vs 28.4%; P < or = 0.05) or with a telophase-I
      chromosome configuration (0.0% vs 8.2%; P < or = 0.0005) was decreased in diamide
      DTT-treated oocytes when compared to diamide-treated oocytes. (ii): Mice were
      fed, from the first day of weaning until their death, a diet supplemented or not
      with an antioxidant mixture of vitamin C and vitamin E. Ovulated oocytes were
      fixed and stained with DAPI or C-banded for chromosome analysis. The percentage
      of abnormal (chromosome scattering and nulloploidy) or asynchronous (anaphase I
      or telophase I) oocytes was 2.7-fold higher in controls than in females fed an
      antioxidant diet (24.4% vs 8.9%, P < or = 0.05). Furthermore, the percentage of
      aneuploidy (2.2% vs 0.0%; P < or = 0.01) and diploidy (5.8% vs 1.7%; P < or =
      0.05) was significantly higher in controls than in females fed an antioxidant
      diet. These findings support Tarin's oxidative stress hypothesis of aneuploidy
      and have clinical implications for preventing both laboratory-induced and
      maternal-age-associated aneuploidy in human beings.

PMID- 9570275
TI  - Cortical granules reaction after intracytoplasmic sperm injection.
AB  - The cortical reaction (CR) in mammalian oocytes is induced following sperm-egg
      membrane fusion. During intracytoplasmic sperm injection (ICSI) the physiological
      cascade of gamete interaction events is bypassed. The aim of this study was to
      explore CR occurrence after the ICSI procedure and its correlation with the
      meiotic status of the oocytes. Unfertilized and abnormally fertilized (one- or
      three-pronucleate) human oocytes were investigated. The chromosomal status was
      analysed by Hoechst staining. The CR occurrence and its fluorescent pattern were
      assessed by confocal scanning laser microscope using the lectin lens culinaris
      and Texas Red staining. Our results reveal a positive correlation between the
      activation of oocytes and their CR. No CR was demonstrated in unfertilized
      unactivated oocytes with or without sperm in their cytoplasm. In partially
      activated oocytes showing resumption of meiosis but no formation of pronuclei, a
      moderate CR was observed. In fully activated oocytes displaying one or three
      pronuclei, a strong CR was monitored. It was concluded that in ICSI, as in
      physiological fertilization, oocyte activation is a prerequisite for CR.

PMID- 9570276
TI  - Effects of monoclonal antibody directed to LeY on implantation in the mouse.
AB  - The role of carbohydrates in embryo implantation in the mouse was investigated
      using an embryo transfer model and a blastocyst-uterine epithelial cell co
      culture system. The monoclonal antibody (mAb) AH6 directed to LeY oligosaccharide
      (Fuc alpha1-2 Gal beta 1-4 [Fuc alpha1-3] GlcNAc) and other three mAbs directed
      to carbohydrates whose structures are closely related to LeY were used to show
      the effect of carbohydrate specificity on implantation. In the embryo transfer
      model, donor blastocysts (4 days post-coitus) were pretreated with mAb AH6
      (experimental) or other mAbs (control) and transferred into one uterine horn of a
      recipient. The implantation rate was checked after 5 days. Implantation was
      significantly inhibited by mAb AH6 pretreatment, and inhibition was not observed
      in control groups. In the co-culture system, the attachment and outgrowth rate of
      blastocysts on the surface of uterine epithelial cells was significantly
      inhibited when monolayer epithelial cells or blastocysts were pretreated with mAb
      AH6. The most obvious effect of mAb AH6 was obtained during 2-4 h co-incubation.
      No inhibition was observed in the control groups. It was, therefore, concluded
      that oligosaccharide LeY recognized by mAb AH6 plays an essential role at the
      initial stage of implantation. It may act as a mediator molecule for adhesion
      between the surface of blastocyst and epithelial cell, and its function is
      carbohydrate-specific.

PMID- 9570277
TI  - Synthesis and regulation of leukaemia inhibitory factor in cultured bovine
      oviduct cells by hormones.
AB  - Leukaemia inhibitory factor (LIF) is an essential factor for embryo implantation.
      Factors generated by the oviduct cells (epithelial cells and fibroblasts) create
      the microenvironment for fertilization and first embryo stage development. Hence,
      it is feasible that the oviduct cells also synthesize LIF to promote and
      condition the embryo for implantation in the uterus. In the present study, we
      investigated whether cultured bovine oviduct epithelial cells and fibroblasts
      synthesize LIF. LIF production was measured in the conditioned medium of oviduct
      epithelial cells and fibroblasts, using LIF enzyme-linked immunosorbent assay.
      Moreover, expression of LIF mRNA was confirmed by LIF reverse transcriptase
      polymerase chain reaction in extracts of RNA from oviduct epithelial/fibroblast
      cells. Quantitatively similar amounts of LIF were detected in the culture medium
      of epithelial cells and fibroblasts. In cells cultured for 1-7 days, the levels
      of LIF in the medium increased in a time-dependent manner. As compared to
      untreated cells, treatment of cells with 17beta-oestradiol (1-100 ng/ ml), but
      not progesterone (1-100 ng/ml) and insulin (20 ng/ml), increased the levels of
      LIF in a concentration-dependent manner (P < 0.05). Similarly, tumour necrosis
      factor-alpha (100 ng/ml) significantly induced the levels of LIF. The effects of
      17beta-oestradiol (50 ng/ml) on LIF synthesis were enhanced and not blocked in
      the presence of tamoxifen (1 microg/ml), an oestrogen receptor antagonist,
      suggesting that the stimulatory effects of 17beta-oestradiol on LIF synthesis are
      not receptor-mediated. In conclusion 17beta-oestradiol, but not progesterone,
      induces LIF synthesis by bovine oviduct epithelial cells and fibroblasts and this
      may play an important role in the biology of early embryo development. However,
      the exact pathophysiological role of LIF within the oviduct needs to be further
      investigated.

PMID- 9570278
TI  - Production of a diverse repertoire of human antibodies in genetically engineered
      mice.

PMID- 9570279
TI  - Tinctorial properties of spherical bodies in broth cultures of Nocardia
      asteroides GUH-2.
AB  - In yeast extract-supplemented brain heart infusion (BHI) broth cultures of
      Nocardia asteroides GUH-2, many spherical bodies (SBs) were frequently seen
      nearby filamentous cells. They showed no gram-positivity when Gram stain was
      applied. When acridine orange stain was applied, many of them showed different
      green fluorescence from bright orange fluorescence of the filamentous nocardiae
      under ultraviolet light. Their acid-fastness appeared to depend on the presence
      of paraffin. Using the polymerase chain reaction (PCR) method, 16S rRNA genes
      were detected in SB-containing broth cultures inoculated with culture filtrates
      from broth cultures of the strain and identical to that of N. asteroides. These
      results suggest that SBs are cell wall-defective (CWD) forms which result from
      the spontaneous mutation of N. asteroides GUH-2.

PMID- 9570280
TI  - Surface characteristics of gram-negative and gram-positive bacteria in an atomic
      force microscope image.
AB  - Bacterial images can be obtained rather easily with an atomic-force microscope
      (AFM) in the magnification range of 5,000 to 30,000 times without any
      pretreatment of the specimens for such observations as chemical fixation,
      dehydration or staining. The bacterial shapes or the presence of flagella can be
      clearly recognized in these magnification ranges. In addition, we were also able
      to distinguish between gram-negative and gram-positive bacteria based on the
      specific wavy surface appearance of the former. AFM could thus be a useful tool
      for the identification of bacteria in the resolution range between electron and
      light microscopy.

PMID- 9570281
TI  - Resistance to oxyimino beta-lactams due to a mutation of chromosomal beta
      lactamase in Citrobacter freundii.
AB  - The duplicative mutation of an Ala-Val-Arg sequence at positions 208 to 210 in
      the loop structure of Enterobacter cloacae class C beta-lactamase caused
      substrate specificity extension to oxyimino beta-lactam antibiotics and this
      chromosomal mutation provided bacterial cells with high resistance to the beta
      lactams (M. Nukaga et al, 1995, J. Biol. Chem. 270, 5729-5735). In order to
      confirm the universality of this phenomenon among other class C beta-lactamases,
      the duplicative mutation was applied to a class C beta-lactamase of Citrobacter
      freundii, which has 74% homology to the E. cloacae beta-lactamase amino acid
      sequence. The counterpart sequence to the Ala-Val-Arg of the E. cloacae enzyme in
      C. freundii beta-lactamase was identified to be Pro-Val-His. A Pro-Val-His
      sequence was inserted just after the native Pro-Val-His sequence at positions 208
      to 210 in the C. freundii beta-lactamase. The resulting mutant of C. freundii
      beta-lactamase obtained a striking characteristic that we expected, showing
      substrate specificity extension to oxyimino beta-lactams. Nearly the same result
      was obtained with the insertion of an Ala-Val-Arg sequence after the native Pro
      Val-His sequence. These results indicate that structural modification of this
      locus commonly induces modification of the substrate specificity to unfavorable
      substrates for many chromosomal class C beta-lactamases produced by gram-negative
      bacteria.

PMID- 9570282
TI  - Infectivity and arthritis induction of Borrelia japonica on SCID mice and immune
      competent mice: possible role of galactosylceramide binding activity on
      initiation of infection.
AB  - We investigated the relationship between the binding activity to
      galactosylceramide (GalCer) and the arthritis induction activity of Borrelia
      japonica. The B. japonica strains maintained the ability to induce arthritis in
      inbred C3H/HeN and immunodeficient SCID mice, but the ability was lower than that
      of Borrelia burgdorferi sensu stricto virulent strain 297. Histopathological
      changes were restricted to the joints, and a marked effusion of polymorphonuclear
      neutrophils into the joint space was found. The binding activity of B. japonica
      strains to GalCer was lower than that of the virulent strain 297 but higher than
      that of the high-passage strain 297. The lower infectivity and virulence of B.
      japonica may explain its lower binding ability to GalCer.

PMID- 9570283
TI  - The use of heterologous promoters for adeno-associated virus (AAV) protein
      expression in AAV vector production.
AB  - Although adeno-associated virus (AAV) vectors are potentially useful gene
      transfer vehicles for gene therapy, the vector production system is currently at
      the developmental stage. We constructed AAV helper plasmids (Rep and Cap
      expression plasmids) by replacing a native AAV promoter, p5, with various
      heterologous promoters to examine whether the efficiency of AAV vector production
      was influenced by modulating the AAV protein expression pattern. The helper
      plasmids containing heterologous promoters (EF, CMV, SV40, B19p6, and CAG
      promoters, respectively) expressed Rep78/68 more efficiently than a conventional
      helper plasmid (pIM45), but the expression of Rep52/40 and Cap decreased,
      resulting in a significant reduction in AAV vector production. Furthermore, the
      efficiency of vector production never fully recovered even if the Cap proteins
      were supplied by an additional expression plasmid. A large amount of Rep78/68
      and/or a reduced level of Rep52/40 may have deleterious effects on AAV vector
      production. The present findings will aid in the development of a more efficient
      AAV vector production system.

PMID- 9570284
TI  - Antigenic and functional analyses of glycoprotein of rabies virus using
      monoclonal antibodies.
AB  - Thirty-five monoclonal antibodies (MAbs) against glycoprotein (G protein) of the
      RC-HL strain of the rabies virus have been established. Using these MAbs, two
      antigenic sites (I and II) were delineated on the G protein of the RC-HL strain
      in a competitive binding assay. Of these, 34 MAbs recognized the epitopes on site
      II. Site II was further categorized into 10 subsites according to their patterns
      in a competitive binding assay. Each site II-specific MAb showed 5 to 23
      nonreciprocal competitions. The reactivities of 35 MAbs to rabies and rabies
      related viruses in an indirect immunofluorescent antibody test showed that six
      MAbs in group A binded to rabies and rabies-related viruses and eight MAbs in
      group E reacted only with rabies viruses, considering that the former represent
      the genus-specific of Lyssavirus and the latter are rabies virus-specific. From
      biological assays, 28 of the 35 MAbs showed neutralization activity, 31 showed
      hemagglutination inhibition (HI) activity, and 18 showed immunolysis (IL)
      activity. The MAbs recognizing neutralization epitopes fell into at least three
      groups: those exhibiting both HI and IL activity, those showing only HI activity,
      and those showing neither HI nor IL activity. All IL epitopes overlap with HA
      epitopes. Five of the nine MAbs which reacted with the antigen treated by sodium
      dodecyl sulfate in ELISA were not reduced, or reduced only slightly, in the
      titer. None of the MAbs reacted with 2-mercaptoethanol-treated antigen. Only one
      MAb that recognized site I reacted with the denatured G protein in a Western
      blotting assay, indicating that its epitope is linear. These results suggest that
      almost all of the epitopes on the G protein of the rabies virus are conformation
      dependent and the G protein forms a complicated antigenic structure.

PMID- 9570285
TI  - Construction of the chimeric reverse transcriptase of simian immunodeficiency
      virus sensitive to nonnucleoside reverse transcriptase inhibitor.
AB  - A number of structurally diverse compounds have been shown to be potent
      inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT). The compounds can be grouped into two broad
      classes; nucleoside analogs and nonnucleoside RT inhibitors. The nonnucleoside RT
      inhibitors are quite specific for HIV-1 RT but not human immunodeficiency virus
      type 2 (HIV-2) and simian immunodeficiency virus (SIV) RT. We have investigated
      the property of SIV/HIV-1 chimeric viruses in which portions of SIV(MAC) RT were
      exchanged with the corresponding domain of HIV-1 RT; amino acids 176-190, 176-383
      and 176-495 of HIV-1 RT. The chimeric virus, which was substituted amino acids
      176-190 of RT, had detectable RT activity, and this chimeric RT was sensitive to
      three nonnucleoside RT inhibitors [nevirapine, HEPT derivative (E-EBU-dM) and
      TIBO derivative (R82913)]. To further study this chimeric virus, we purified the
      chimeric RT enzyme expressed in Escherichia coli and determined its kinetic
      properties; the Km, and Vmax values, and the Ki value of HEPT derivative
      calculated for the DNA polymerase activity. This study reveals that amino acids
      176-190 of SIV(MAC) RT were important for the enzymatic activity and the SIV/HIV
      1 chimeric RT, which had amino acids 176-190 of HIV-1, was sensitive to the
      nonnucleoside RT inhibitor.

PMID- 9570286
TI  - Protective effect of administration of skim milk on exogenous and endogenous
      infection in mice.
AB  - In order to minimize the denaturation of proteins in milk, normal cow's milk was
      pasteurized at 61 C for 20 min. The protective effects of the thus prepared skim
      milk (low-heat skim milk) on exogenous and endogenous infection were examined as
      compared with conventional skim milk which was pasteurized at 121 C for 2 sec.
      The antibody titers to Listeria monocytogenes and Escherichia coli of low-heat
      skim milk were almost equal to that of raw milk, while no antibody was detected
      in the conventional skim milk. When mice were given low-heat skim milk or
      conventional skim milk, the incidence of the translocation of orally inoculated
      Listeria monocytogenes to the spleen was lower in the low-heat skim milk group
      than that in the conventional skim milk group. The life span of 7 Gy X-ray
      irradiated mice given low-heat skim milk was significantly prolonged in
      comparison to that of mice given conventional skim milk. However, there were no
      differences in the number of bacteria in the feces or IgA production by Peyer's
      patch cells between the two groups. These results suggest that antibodies in low
      heat skim milk, which still have reactivity to exogenous or indigenous bacteria,
      may contribute to the protective effects against bacterial infection.

PMID- 9570287
TI  - Kinetical analysis of tumor cell death-inducing mechanism by polymorphonuclear
      leukocyte-derived calprotectin: involvement of protein synthesis and generation
      of reactive oxygen species in target cells.
AB  - We have previously shown that calprotectin, the most abundant cytosolic protein
      existing in polymorphonuclear leukocytes (PMNs), induces apoptotic cell death in
      various tumor cells, suggesting that calprotectin is an effector molecule against
      tumor cells in PMNs. To explore the cell death-inducing mechanism of the factor,
      we examined the involvement of target protein synthesis and generation of
      reactive oxygen species (ROS) in the reaction. Calprotectin induced cell death in
      MM46 mouse mammary carcinoma cells after a 14-16 hr lag time. When the factor was
      removed from the medium up to about 12 hr after culturing, the effect was
      diminished. The induction of cell death by calprotectin was markedly inhibited by
      the presence of the RNA synthesis inhibitor actinomycin D or the protein
      synthesis inhibitor cycloheximide. However, the addition of these inhibitors
      after 12 hr of culturing was unable to inhibit the reaction. Up to 12 hr of
      culturing, the net protein synthesis of MM46 cells was augmented by the presence
      of calprotectin, but thereafter was impaired. The induction of cell death was
      also inhibited by the antioxidative reagents N-acetyl-L-cysteine (NAC) or propyl
      gallate. The addition of NAC even 15 hr later significantly attenuated the
      calprotectin effect. Flow cytometry analysis showed that calprotectin began to
      increase the ROS content in MM46 cells after 8-12 hr of culturing, and that the
      increase was abrogated by the antioxidants. Thus, protein synthesis and ROS
      generation may be essential elements in the early or later phases of the cell
      death-inducing reaction of calprotectin, respectively.

PMID- 9570288
TI  - Discrimination among the clinical isolates of Candida albicans by amplification
      of the repetitive sequences, alts.
AB  - A primer pair, PB and BSH, which amplified alts, a portion of Candida albicans
      specific repetitive sequence, RPS, gave stable and reproducible fingerprint
      patterns of the strains by polymerase chain reaction (PCR). We applied this
      method to clinical isolates of C. albicans for strain discrimination. Using PCR
      fingerprint patterns, we could analyze the relatedness of C. albicans strains
      including those isolated from children with leukemia and their bedside parents.
      The results indicated that PCR analysis targeting an alt region gives rise to the
      same conclusion as the previous study obtained by SmaI RFLP analysis.

PMID- 9570289
TI  - Zymographic characterization of Staphylococcus aureus cell wall.
AB  - Susceptibilities of several preparations of Staphylococcus aureus cells to
      various peptidoglycan hydrolases with known bond specificity were analyzed by
      zymography. The substrates were intact S. aureus cells, cells boiled in the
      presence of SDS and cells treated with trichloroacetic acid after treatment with
      boiling SDS solution (TCA-cells). Twofold dilutions of lysostaphin (LS), lysozyme
      (LZ), S. aureus 51 kDa glucosaminidase (GL) or S. aureus 62 kDa amidase (AM) were
      electrophoresed, and the minimal enzyme dose showing a visible bacteriolytic band
      was defined as MBD (minimal bacteriolytic dose). Under the same experimental
      conditions, this method gave reproducible results. As the substrate for zymogram,
      TCA-cells were the most sensitive to LS, LZ and AM, whereas the three substrate
      were equally sensitive to GL. A zymographic analysis of methicillin-resistant S.
      aureus treated with methicillin together with previous studies suggest that this
      method can be used for the preliminary characterization of S. aureus cell wall
      peptidoglycan.

PMID- 9570290
TI  - Filamentous phage fs1 of Vibrio cholerae O139.
AB  - Filamentous phage, fs1, was obtained from Vibrio cholerae O139. The lysogenized
      strains produced a large amount of fs1 phage in the culture supernatant. This
      phage was previously reported as novel fimbriae of that organism. The genome of
      the phage was a 6.5 kb single-stranded DNA. The capsid of fsl consists of a small
      molecule peptide (about 2.5 kDa).

PMID- 9570291
TI  - Intervening sequences in 16S rRNA genes of Campylobacter sp.: diversity of
      nucleotide sequences and uniformity of location.
AB  - We found and sequenced intervening sequences (IVSs) in the PCR-amplicons of 16S
      rRNA genes of 3 strains of Campylobacter rectus, 2 strains of C. curvus and 2
      strains of C. sputorum. The lengths of the IVSs were 140 to 233 bp. The IVSs of
      C. rectus were identical and had a sequence homology of 55 to 79% against those
      of C. curvus and C. helveticus. The IVSs of C. sputorum were 97.9-100% homologous
      but poorly homologous to the other IVSs. In spite of the diversities of the
      lengths and the nucleotide sequences, all of the IVSs were located at the same
      position in the 16S rRNA genes.

PMID- 9570292
TI  - Escape from host-antitumor immunity.
AB  - Cancer cells may express proteins recognizable by the individual's immune system
      as foreign because they are either tumor-specific or not expressed at high levels
      in normal tissues to which the host is tolerant. There is now much evidence that
      tumors can be immunogenic, that is, that they frequently express antigens in a
      form recognizable by the host immune system. This has been shown not only in
      experimental animals but also for spontaneously occurring human tumors. Tumors
      therefore may progress by evolving variants that can evade immune responses or by
      developing other strategies to "escape" the immune response. The purpose of this
      review is to consider the current status of knowledge concerning these different
      tumor escape strategies.

PMID- 9570293
TI  - Interleukin-1: basic science and clinical applications.

PMID- 9570294
TI  - The Cbl protooncogene product: from an enigmatic oncogene to center stage of
      signal transduction.
AB  - The c-cbl protooncogene was first identified as the cellular homologue of a viral
      oncogene v-cbl that induces pre-B lymphomas and myeloid leukemias in mice. Until
      recently, the biochemical basis for Cbl's transforming potential and its
      physiological role remained unclear. However, a convergence of biochemical
      studies in mammalian cells and genetic studies in C. elegans and Drosophila has
      now identified Cbl as a negative regulator of tyrosine kinase signaling. The N
      terminal transforming region of Cbl (Cbl-N) and an adjacent RING finger domain
      are the elements most conserved during evolution. The Cbl-N region has now been
      shown to contain a novel phosphotyrosine-binding (PTB) domain that directly
      interacts with autophosphorylated tyrosine kinases via a D(N/D)XpY motif. A
      critical role of the PTB domain in Cbl function is demonstrated by the
      localization of a loss-of-function mutation in C. elegans Cbl homologue SLI-1
      within this region. The corresponding mutation in human Cbl inactivates the PTB
      domain function and abrogates Cbl-mediated regulation of tyrosine kinase
      function. Recent studies have also identified a novel signaling pathway initiated
      by the interaction of mammalian Cbl proteins with the SH2 domains of Crk adaptor
      molecules, which results in Cbl's linkage with C3G, a guanine nucleotide exchange
      protein for Rap1 family of small G-proteins. Presently, Rap1 is thought to
      antagonize Ras function, although Rap1-specific targets have emerged recently.
      Thus, recent advances have firmly placed the little known protooncoprotein Cbl on
      the center stage of tyrosine kinase-mediated signal transduction.

PMID- 9570295
TI  - Physical activity and cancer: how may protection be maximized?
AB  - A series of meta-analyses have examined relationships between regular physical
      activity and susceptibility to various forms of cancer. Regular physical activity
      protects animals against cancer from a variety of sources: subcutaneous,
      intraperitoneal or intragastric carcinogens, intravenous infusion of tumor cells,
      or tumor implantation. In humans, regular exercise reduces susceptibility to all
      cause cancer, colonic adenomas, colon but not rectal cancers, breast cancers,
      uterine tumors, prostate and testicular tumors, and possibly lung cancers. At
      most tumor sites, the average response of women is similar to that of men, but
      because of a limited number of studies, the effect in women is commonly
      nonsignificant. The relative effects of occupational and leisure activity are
      generally similar, an observation that suggests that the optimum response of
      cancer defense mechanisms is obtained from moderate levels of energy expenditure.
      In general, the data show a dose-response relationship, the risk of a sedentary
      lifestyle approximately doubling on passing from a moderate to a low level of
      habitual physical activity. To date, the findings have not demonstrated the
      postulated j-shaped relationship, but the cross-sectional comparison of low vs.
      high levels of leisure activity suggests that the adoption of an active lifestyle
      could reduce all-cause cancer rates by as much as 46%.

PMID- 9570296
TI  - HIV-1 vaccine candidate evaluation in non-human primates.
AB  - The development of an HIV-1 vaccine in the last 13 years from an industrial point
      of view has focused on evaluating potential vaccine candidates in non-human
      primates. This review discusses the HIV-1 vaccine candidates that have been
      tested in chimpanzees or monkeys and includes those based on recombinant gp120,
      recombinant gp160, different viral and bacterial vectors expressing gp120, gp160,
      or only V3 peptide, naked DNA vaccines, and whole inactivated viruses. To help
      understand the result of efficacy studies in chimpanzees and monkeys, information
      regarding the challenge viruses used in these studies is also included. The
      review does not discuss the testing of SIV-related vaccines or the testing of HIV
      1 vaccine candidates in other animal species other than non-human primates.

PMID- 9570297
TI  - Impaired tumorigenicity and decreased liver metastasis of murine neuroblastoma
      cells engineered to secrete interleukin-2 or granulocyte macrophage colony
      stimulating factor.
AB  - We have examined the antitumor effect of murine neuroblastoma cells (C1300)
      engineered to produce cytokines. Retrovirally transduced cells with human
      interleukin-2 (IL-2) or murine GM-CSF gene, but not murine IL-4 gene, abolished
      their tumorigenicity in syngeneic mice, although their in vitro growth rate and
      expression of class I antigens of the major histocompatibility complex were
      unchanged. Inoculation of wild-type cells into the mice, which had rejected IL-2
      or GM-CSF producers, did not develop tumors, indicating that protective immunity
      was induced. In an experimental hematogenous metastasis model, we found that the
      numbers of metastatic foci in the liver caused by intravenous administration of
      IL-2 or GM-CSF producers were significantly reduced compared with those by the
      injection of wild-type or vector virus-transduced cells. No significant
      differences in their adhesiveness to extracellular matrices and ability to
      differentiate were observed among parent and transduced cells. Thus, these
      results indicate that IL-2 or GM-CSF secretion, in the vicinity of neuroblastoma
      cells, produced antitumor effect and reduced metastatic ability.

PMID- 9570298
TI  - Local inflammatory response and vector spread after direct intraprostatic
      injection of a recombinant adenovirus containing the herpes simplex virus
      thymidine kinase gene and ganciclovir therapy in mice.
AB  - We have evaluated the safety and potential toxicity of an adenoviral vector
      containing the herpes simplex virus thymidine kinase gene (adenovirus/Rous
      sarcoma virus thymidine kinase in a preclinical model for prostate cancer.
      Clinical grade vector prepared for human trials was injected directly into the
      dorsolateral prostate of C57Bl/6 mice in a volume of 5 microL at doses of 2.5 x
      10(6), 2.5 x 10(7), or 2.5 x 10(8). The mice received intraperitoneal injections
      of either ganciclovir or saline twice daily for 6 days, beginning 12 hours after
      vector injection. Representative tissues and fluids were collected for evaluation
      the day after the final dose. Microscopic pathologic evaluation revealed
      inflammatory infiltration without necrosis within the dorsolateral and ventral
      prostate, but no necrosis or leukocyte infiltration was observed in sample
      tissues from lung, liver, large intestine, bladder, seminal vesicle, testis, or
      epididymis. DNA was extracted from the above tissues as well as pelvic lymph
      nodes, blood, seminal fluid, urine, and sperm and analyzed by polymerase chain
      reaction for the presence of vector sequences. The vector was readily detected in
      the dorsolateral prostate, the site of injection. The amount of vector detected
      was reduced in some samples from ganciclovir-treated animals. At the highest
      dose, vector spread was observed in the ventral prostate, seminal vesicle,
      testis, pelvic lymph nodes, gut, and liver. Spread to the testis was observed in
      only one animal. Vector DNA was not detected in urine, seminal fluid, or sperm
      but was detected in the blood of one animal. This adenoviral vector, therefore,
      appears to have minimal spread to sites distant from the site of injection and no
      detectable pathological sequelae within this dose range in this preclinical model
      for prostate cancer, which may be generalizable to other solid tumors.

PMID- 9570299
TI  - Phosphorylation and cytotoxicity of therapeutic nucleoside analogues: a
      comparison of alpha and gamma herpesvirus thymidine kinase suicide genes.
AB  - Thymidine kinase (TK) genes from three alpha-herpesviruses (i.e., human herpes
      simplex type 1, varicella-zoster virus, equid herpesvirus 4) and two y
      herpesviruses (i.e., Epstein-Barr virus and Saimiri herpesvirus 2) were cloned in
      expression vectors based on zeocin resistance by complementation of a TK
      defective Escherichia coli strain. In vivo complementation of an appropriate
      yeast strain and in vitro enzymatic measurements demonstrated that all viral TKs
      possess a second phosphorylating activity corresponding to the thymidylate kinase
      function in contrast to the E coli TK, which is deprived of this activity. When
      expressed in an engineered E coli strain rendered resistant to purine and
      pyrimidine nucleoside analogs, the viral TKs sensitize host bacteria to 3'-azido
      3'-deoxythymidine (AZT), 3'-deoxy-2',3'-didehydrothymidine (D4T), dideoxyinosine,
      or fluorodeoxyuridine (5-FUdR). The extent of activation of all these analogs, in
      this bacterial assay, was found to be greatly superior for the two gamma-virus
      TKs, compared to the alpha-virus TKs, including the reference suicide gene, HSV1
      TK. TK from the two gamma-Epstein-Barr and Saimiri 2 viruses were also found to
      be more efficient in sensitizing murine melanoma B16 tumor cells to pyrimide
      nucleoside analogs.

PMID- 9570300
TI  - Does preventive vaccination with engineered tumor cells work in cancer-prone
      transgenic mice?
AB  - The use of genetically modified tumor cells as vaccines has been successful in
      numerous animal models of grafted syngenic tumors and has provided the groundwork
      for many clinical trials of gene therapy in cancer patients. To investigate the
      real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice
      that express the SV40 large T and small t antigens under the control of hepatic
      antithrombin III (ASV-B)-regulatory sequences. These mice systematically develop
      hepatocarcinoma. Hepatoma cells, derived from ASV-B transgenic mice, were gene
      transduced to express either interleukin-2, interleukin-4, the granulocyte
      macrophage colony-stimulating factor, or the T-cell costimulatory molecule B7.1.
      First, we demonstrated the vaccine potential of engineered hepatoma cells by
      immunizing nontransgenic mice with these cells, which prevented the growth of
      subsequent grafted nontransduced hepatoma cells. However, vaccination of
      pretumoral transgenic animals with various combinations of engineered hepatoma
      cells failed to inhibit hepatoma onset and progression. Rather, tumor development
      in ASV-B mice appears to be dependent on the immune system, since neonatal
      induction of immunotolerance to tumor in ASV-B mice cells was associated with a
      moderate, but significant, acceleration of tumor development. These results
      seriously call into question the efficacy of this strategy of active
      vaccinotherapy against natural tumors.

PMID- 9570301
TI  - Monitoring thymidine kinase and ganciclovir-induced changes in rat malignant
      glioma in vivo by nuclear magnetic resonance imaging.
AB  - We have used high resolution magnetic resonance imaging to monitor malignant rat
      BT4C gliomas in vivo following herpes simplex virus thymidine kinase gene and
      ganciclovir (GCV) treatment. Twenty-six female BDIX rats were used for the study
      including four controls. Serial magnetic resonance imaging was performed every 72
      hours to quantify tumor volume, transverse relaxation time (T2) ,and apparent
      diffusion constant (ADC) of water in the tumors and in the contralateral brain.
      GCV treatment was given twice a day, intraperitoneally, for 21 days. The gliomas
      exhibited low T2 and ADC values (before treatment), compared to normal brain,
      indicating the presence of high cell density tumors. Following GCV treatment, a
      regional increase in T2 and ADC was observed as early as day 4 of the treatment,
      even though the tumor volume was still increasing. These observations suggested
      evolution of local necroses which were confirmed by histology. In a group of five
      tumor bearing rats, retrovirus-producing packaging cell injections were given
      intratumorally to mimic clinically relevant gene therapy. In these cases, only
      small and short-lasting T2 and ADC elevations were found following GCV treatment
      without an effect on the overall tumor growth and outcome. Our results show that
      quantitative magnetic resonance imaging including T2 and ADC, is superior to
      robust volume measurements in predicting an early response to retrovirus-mediated
      gene therapy in vivo.

PMID- 9570302
TI  - Immunization with interleukin-2-secreting allogeneic cells transfected with DNA
      from mouse melanoma cells induces immune responses that prolong the lives of mice
      with melanoma.
AB  - Altered genes in tumor cells specify tumor-associated antigens. Because genetic
      instability is a characteristic of the malignant cell phenotype, a large number
      of different, altered genes may be present in a population of neoplastic cells,
      specifying an array of undefined tumor-associated determinants. We hypothesized
      that immunogenic cells transfected with DNA from malignant cells will include
      cells that specify tumor-associated antigens. To test this question, we
      deliberately mutagenized a population of B16 melanoma cells (H-2b) by ultraviolet
      B irradiation. DNA from the surviving cells was used to transfect LM cells (H
      2k), a mouse fibroblast cell line modified previously to secrete interleukin-2.
      The transfected allogeneic cells were then tested for their immunogenic
      properties in C57BL/6J mice (H-2b) syngeneic with the melanoma. Mice injected
      with a mixture of the mutagenized B16 cells and the transfected cells survived
      significantly longer than untreated mice injected with the mutagenized B16 cells
      alone. Mice injected with a mixture of mutagenized B16 cells and cells
      transfected with DNA from unirradiated B16 cells died in shorter intervals. Based
      on the results of cytotoxicity assays performed in vitro, the cellular immune
      responses of greatest magnitude were directed toward the type of cell from which
      the DNA was obtained.

PMID- 9570303
TI  - Transfection of primary tumor cells and tumor cell lines with plasmid DNA/lipid
      complexes.
AB  - Cancer vaccines that utilize genetically modified tumor cells require gene
      transfer methods capable of producing immunostimulatory doses of transgenes from
      fresh or short-term cultures of human tumor cells. Our studies optimize in vitro
      transfection of primary tumor cells using cationic lipids and a plasmid encoding
      the gene for human interleukin-2 (IL-2). Established tumor cell lines produced 10
      to 100-fold more IL-2 than did fresh or short-term tumor cultures as measured by
      enzyme-linked immunoabsorbent analysis. Importantly, transfection of primary
      tumor cells produced immunostimulatory levels of IL-2 as determined by increased
      thymidine incorporation by autologous peripheral blood mononuclear cells and
      lymphokine-activated killer cell activity. IL-2 secretion by tumor cells
      persisted for at least 30 days post-transfection and was unaffected by freeze
      thawing or irradiation to 8000 rads. Multiple solid tumor types were successfully
      transfected, but normal blood mononuclear cells and leukemic blasts were
      resistant to transfection. Enzyme-linked immunoabsorbent analysis of the amount
      of IL-2 secreted into the medium by transfected tumor cells correlated with the
      percentage of tumor cells expressing intracellular IL-2 as measured by flow
      cytometry. Plasmids utilizing a cytomegalovirus promoter yielded superior
      transfection efficiencies compared with plasmids containing a Rous sarcoma virus
      promoter. These results suggest that a clinical vaccine trial using autologous
      tumor cells genetically modified to secrete IL-2 is feasible in patients with
      solid tumors.

PMID- 9570305
TI  - A case-control study of lung cancer mortality in four rural Arizona smelter
      towns.
AB  - To investigate factors related to lung cancer mortality in four Arizona copper
      smelter towns, the authors identified 142 lung cancer cases and 2 matched
      controls per case from decedent residents during 1979-1990. The authors obtained
      detailed information on lifetime residential, occupational, and smoking histories
      via structured telephone interviews with knowledgeable informants. The authors
      linked estimated historical environmental exposures to smelter emissions (based
      on atmospheric diffusion modeling of measured sulfur dioxide concentrations) with
      residential histories to derive individual profiles of residential exposure. The
      results of this study provided little evidence of a positive association between
      lung cancer and residential exposure to smelter emissions. Conditional logistic
      regression analysis revealed a statistically significant positive association
      between lung cancer and reported employment in copper mines and/or smelters,
      although specific factors associated with the apparently increased risk among
      these workers could not be identified in this community-based study.

PMID- 9570304
TI  - Neurophysiological function in farm workers exposed to organophosphate
      pesticides.
AB  - To investigate neurophysiological effects of low-level exposure to foliar
      organophosphate residues during one season among agricultural workers, the
      authors performed a cross-sectional study of 67 Hispanic farm workers and 68 age
      , gender-, ethnicity-, and education-matched reference subjects. The
      neurophysiological examination included sensory and motor nerve conduction and
      neuromuscular junction testing. Erythrocyte cholinesterase activity was measured
      at the time of examination. No statistically significant neurophysiological
      differences between the exposed and reference groups were observed. Farm workers
      and reference subjects had similar sensory nerve latency and amplitude (sural),
      motor nerve conduction velocity (ulnar), and neuromuscular junction function
      (ulnar). No relationship between duration of exposure during the season and
      electrophysiological measures of nerve function was found. Exposure of farm
      workers to the low levels of organophosphate pesticides during one season
      experienced by farm workers in this study was not associated with impaired
      peripheral neurophysiological function.

PMID- 9570306
TI  - Poverty, production, and health: inhibition of erythrocyte cholinesterase via
      occupational exposure to organophosphate insecticides in Chiapas, Mexico.
AB  - Occupational exposure to organophosphate pesticides and its effects on the
      concentration of erythrocyte cholinesterase in the rural population of Chiapas,
      Mexico, are described. The authors surveyed agricultural production and pesticide
      use was surveyed among 199 campesinos (peasants) in three communities that used
      various agricultural production systems. The authors measured the concentration
      of the cholinesterase enzyme in blood samples obtained from 65 campesinos before
      and after exposure to the insecticide. The authors established a comparison value
      for the population that was not exposed occupationally. The exposure values of
      the enzyme concentration were significantly lower than preexposure values (p =
      .00001) and reference group values (p = .0008). Individuals in the community
      characterized by subsistence production had significantly lower levels of the
      enzyme than individuals in the other two communities (p = .01). This result
      suggested that a greater risk of adverse health effects existed among the poorest
      communities.

PMID- 9570307
TI  - Hair mercury levels of residents in China, Indonesia, and Japan.
AB  - The authors used gold-amalgamation cold-vapor atomic absorption spectrometry and
      ECD-gas chromatography to analyze total mercury and methylmercury levels in hair
      samples obtained from 362 residents in Harbin, China; Medan, Indonesia; and
      Tokushima, Japan. In this study, the authors initially questioned whether mercury
      levels in hair differed among different study areas, and if there were
      differences, they questioned the contributing factors. In the three countries
      surveyed, total mercury and methylmercury levels in hair were lowest in residents
      of China and were highest in residents of Japan. In the district of Tokushima,
      Japan, total mercury and methylmercury levels were highest in the coastal
      district, followed by the middle district; the lowest levels occurred in the
      mountainous district. In Japan, an individual's total mercury level correlated
      very closely with that person's methylmercury level; in China and Indonesia, the
      correlation between these 2 parameters was low. No subjects in China or Indonesia
      had high levels of methylmercury in hair; this was true even if their total
      mercury levels were high. This finding suggests that the high total mercury
      levels observed in some residents of China and Indonesia reflected exposure to
      inorganic mercury. In Japan, mercury (especially methylmercury) levels in hair
      samples were quite high. Fish and shellfish, caught in seas uncontaminated by
      human activity, appeared to be major sources of the high levels of hair mercury
      in Japanese subjects.

PMID- 9570308
TI  - Synergistic effects of air pollution and personal smoking on adult pulmonary
      function.
AB  - There is strong evidence that air pollution and cigarette smoking adversely
      affect respiratory health, but it remains uncertain whether the joint effects of
      air pollution and smoking are additive or synergistic. The authors investigated
      the hypothesized synergistic effects of air pollution and personal smoking on
      pulmonary function in a random sample of 3287 adults (40-69 y of age) who resided
      in residential, industrial, and suburban areas in Beijing. The authors used
      multiple linear regression and adjusted for age, sex, height, education, indoor
      use of coal stoves, crowding within a house, occupational exposures, and passive
      smoking. The annual mean total suspended particulates for the period 1981-1985 in
      residential, industrial, and suburban areas were 389 microg/m3, 449 microg/m3,
      and 261 microg/m3, respectively, and the annual mean sulfur dioxide levels were
      128 microg/m3, 57 microg/m3, and 18 microg/m3, respectively. Compared with
      individuals in the suburban area, never smokers who resided in the industrial
      area had a 26-ml (standard error = 39) reduction in forced expiratory volume in 1
      s and a 150-ml (standard error = 42) reduction in forced vital capacity; however,
      smokers in the same area suffered an additional 53-ml (standard error = 38)
      reduction in forced expiratory volume in 1 s and a 65-ml (standard error = 41)
      reduction in forced vital capacity. Similarly, never-smokers who resided in the
      residential area had a 72-ml (standard error = 35) reduction in forced expiratory
      volume in 1 s and a 274-ml (standard error = 38) reduction in forced vital
      capacity, and smokers in the same area suffered an additional 75-ml (standard
      error = 39) reduction in forced expiratory volume in 1 s and a 107-ml (standard
      error = 42) reduction in forced vital capacity. Long-term exposure to high levels
      of particulate and sulfur dioxide in Beijing was associated with significantly
      reduced pulmonary function in both never smokers and smokers. However, the
      associations were significantly greater among smokers than among never smokers,
      indicating a synergistic effect of air pollution and personal smoking on adult
      pulmonary function.

PMID- 9570309
TI  - Short-term effects of air pollution on hospital admissions of respiratory
      diseases in Europe: a quantitative summary of APHEA study results. Air Pollution
      and Health: a European Approach.
AB  - The Air Pollution and Health: a European Approach (APHEA) project is a
      coordinated study of the short-term effects of air pollution on mortality and
      hospital admissions. Five West European cities (i.e., London, Amsterdam,
      Rotterdam, Paris, Milano) contributed several years of hospital admissions data
      for all respiratory causes. In the current study, the authors describe the
      results obtained from the quantitative pooling (meta-analysis) of local analyses.
      The diagnostic group was defined by ICD 460-519. The age groups studied were 15
      64 y (i.e., adults) and 65+ y (elderly). The air pollutants studied were sulfur
      dioxide; particles (i.e., Black Smoke or total suspended particles); ozone; and
      nitrogen dioxide. The pollutants were obtained from existing fixed-site monitors
      in a standardized manner. We used Poisson models and standardized confounder
      models to examine the associations between daily hospital admissions and air
      pollution. We conducted quantitative pooling by calculating the weighted means of
      local regression coefficients. We used a fixed-effects model when no
      heterogeneity could be detected; otherwise, we used a random-effects model. When
      possible, the authors investigated the factors correlated with heterogeneity. The
      most consistent and strong finding was a significant increase of daily admissions
      for respiratory diseases (adults and elderly) with elevated levels of ozone. This
      finding was stronger in the elderly, had a rather immediate effect (same or next
      day), and was homogeneous over cities. The elderly were affected more during the
      warm season. The Sulfur dioxide daily mean was available in all cities, and it
      was not associated consistently with an adverse effect. Effects were present in
      areas in which more than one station was used in the assessment of daily
      exposure. Some significant associations were observed, although no conclusion
      that related to an overall particle effect could be drawn. The effect of Black
      Smoke was significantly stronger with high nitrogen dioxide levels on the same
      day, but nitrogen dioxide itself was not associated with admissions. The ozone
      results were in good agreement with the results of similar U.S. studies. The
      coherence of the results of this study and other results gained under different
      conditions strengthens the argument for causality.

PMID- 9570311
TI  - Electrical occupations and neurodegenerative disease: analysis of U.S. mortality
      data.
AB  - Investigators have hypothesized that occupations involving electric and magnetic
      field exposure are associated with a variety of health problems, including
      neurological disease. The authors conducted a case-control study, and they used
      U.S. death certificates with occupational coding to compare male cases of
      Alzheimer's disease (n = 256), Parkinson's disease (n = 168), and amyotrophic
      lateral sclerosis (n = 114) with controls matched for age and calendar time. The
      authors selected controls in a 3:1 ratio to cases from persons who died of causes
      other than leukemia, brain cancer, and breast cancer. Overall associations with
      electrical occupations were modest (i.e., adjusted odds ratios of 1.2, 1.1, and
      1.3 for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral
      sclerosis, respectively). Individual electrical occupations were associated more
      strongly with disease than overall electrical occupations, particularly
      amyotrophic lateral sclerosis, for which relative risks ranged from 2 to 5 across
      several job categories. The largest associations with all three diseases occurred
      for power plant operators.

PMID- 9570310
TI  - Brain cancer mortality among French farmers: the vineyard pesticide hypothesis.
AB  - In this study, the authors assessed the contribution of vineyard pesticides to
      brain cancer mortality among agricultural workers. A pesticide exposure index
      (PEI) in vineyards was calculated for 89 French geographical units
      (departements). The authors estimated standardized mortality ratios among male
      farmers and farm laborers aged 35-74 y for the years 1984-1986. Poisson
      regression models, which were fitted to the ecological data, included random
      effects. Mortality from brain cancer among farmers was significantly higher than
      mortality for the overall population (standardized mortality ratio = 1.25, p <
      .001). Univariate analysis revealed a significant link with pesticide exposure in
      vineyards (relative risk = 1.10; 95% confidence interval = 1.03, 1.18), as did
      multivariate analysis (relative risk = 1.11; 95% confidence interval = 1.03,
      1.19). These results corraborate the evidence that pesticides in vineyards
      contribute to mortality from brain cancer among farmers.

PMID- 9570312
TI  - Reducing lead exposure by surveillance system: the Taiwan experience.
AB  - To evaluate the performance of a lead-surveillance program in reducing blood lead
      levels of workers in Taiwan, the authors conducted prospective and cross
      sectional studies. A total of 6 905 workers, whose job titles indicated a direct
      exposure to lead in 1995, were included in this surveillance system. In this
      study, the authors compared the mean blood lead levels in 1994 (i.e., year of
      onset of surveillance) with that in 1995 in workers of major industries. Lead
      exposed workers had a statistically significant decrease (i.e., average of 1.8
      microg/dl) in blood lead levels during this 1-y period. The decrease was
      particularly obvious in individuals who worked in chemical products
      manufacturing, ship building/repairing, and plastic products manufacturing. The
      significant decreases in blood lead levels in these workers indicated that this
      surveillance system was effective. Surveillance, combined with control measures,
      might be an important means by which occupational lead exposure can be reduced.

PMID- 9570313
TI  - The 20kD protein of human [U4/U6.U5] tri-snRNPs is a novel cyclophilin that forms
      a complex with the U4/U6-specific 60kD and 90kD proteins.
AB  - Cyclophilins (Cyps) catalyze the cis/trans isomerization of peptidyl-prolyl
      bonds, a rate-limiting step in protein folding. In some cases, cyclophilins have
      also been shown to form stable complexes with specific proteins in vivo and may
      thus also act as chaperone-like molecules. We have characterized the 20kD protein
      of the spliceosomal 25S [U4/U6.U5] tri-snRNP complex from HeLa cells and show
      that it is a novel human cyclophilin (denoted SnuCyp-20). Purified [U4/U6.U5] tri
      snRNPs, but not U1, U2, or U5 snRNPs, exhibit peptidyl-prolyl cis/trans isomerase
      activity in vitro, which is cyclosporin A-sensitive, suggesting that SnuCyp-20 is
      an active isomerase. Consistent with its specific association with tri-snRNPs in
      vitro, immunofluorescence microscopy studies showed that SnuCyp-20 is
      predominantly located in the nucleus, where it colocalizes in situ with typical
      snRNP-containing structures referred to as nuclear speckles. As a first step
      toward the identification of possible targets of SnuCyp-20, we have investigated
      the interaction of SnuCyp-20 with other proteins of the tri-snRNP. Fractionation
      of RNA-free protein complexes dissociated from isolated tri-snRNPs by treatment
      with high salt revealed that SnuCyp-20 is part of a biochemically stable
      heteromer containing additionally the U4/U6-specific 60kD and 90kD proteins. By
      coimmunoprecipitation experiments performed with in vitro-translated proteins, we
      could further demonstrate a direct interaction between SnuCyp-20 and the 60kD
      protein, but failed to detect a protein complex containing the 90kD protein. The
      formation of a stable SnuCyp-20/60kD/90kD heteromer may thus require additional
      factors not present in our in vitro reconstitution system. We discuss possible
      roles of SnuCyp-20 in the assembly of [U4/U6.U5] tri-snRNPs and/or in
      conformational changes occurring during the splicing process.

PMID- 9570314
TI  - The Drosophila splicing regulator sex-lethal directly inhibits translation of
      male-specific-lethal 2 mRNA.
AB  - Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls
      dosage compensation in Drosophila. msl-2 gene expression is inhibited in females
      by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing.
      An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains
      putative SXL binding sites and is retained in female flies. Here we show that SXL
      plays a dual role in the inhibition of msl-2 expression. Cotransfection of
      Drosophila Schneider cells with an SXL expression vector and a reporter
      containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron
      and efficient accumulation of the unspliced mRNA in the cytoplasm, where its
      translation was blocked by SXL, but not by the intron per se. Both splicing and
      translation inhibition by SXL were recapitulated in vitro and found to be
      dependent upon SXL binding to high-affinity sites within the intron, showing that
      SXL directly regulates these events. Our data reveal a coordinated mechanism for
      the regulation of msl-2 expression by the same regulatory factor: SXL enforces
      intron retention in the nucleus and subsequent translation inhibition in the
      cytoplasm.

PMID- 9570315
TI  - Domain 5 binds near a highly conserved dinucleotide in the joiner linking domains
      2 and 3 of a group II intron.
AB  - Photocrosslinking has identified the joiner between domains 2 and 3 [J(23)] as
      folding near domain 5 (D5), a highly conserved helical substructure of group II
      introns required for both splicing reactions. D5 RNAs labeled with the
      photocrosslinker 4-thiouridine (4sU) reacted with highly conserved nucleotides
      G588 and A589 in J(23) of various intron acceptor transcripts. These conjugates
      retained some ribozyme function with the lower helix of D5 crosslinked to J(23),
      so they represent active complexes. One partner of the gamma x gamma' tertiary
      interaction (A587 x U887) is also in J(23); even though gamma x gamma' is
      involved in step 2 of the splicing reaction, D5 has not previously been found to
      approach gamma x gamma'. Similar crosslinking patterns between D5 and J(23) were
      detected both before and after step 1 of the reaction, indicating that the lower
      helix of D5 is positioned similarly in both conformations of the active center.
      Our results suggest that the purine-rich J(23) strand is antiparallel to the D5
      strand containing U32 and U33. Possibly, the interaction with J(23) helps
      position D5 correctly in the ribozyme active site; alternatively, J(23) itself
      might participate in the catalytic center.

PMID- 9570316
TI  - Genetic interaction between U6 snRNA and the first intron nucleotide in
      Saccharomyces cerevisiae.
AB  - Nuclear pre-mRNA splicing necessitates specific recognition of the pre-mRNA
      splice sites. It is known that 5' splice site selection requires base pairing of
      U6 snRNA with intron positions 4-6. However, no factor recognizing the highly
      conserved 5' splice site GU has yet been identified. We have tested if the known
      U6 snRNA-pre-mRNA interaction could be extended to include the first intron
      nucleotides and the conserved 50GAG52 sequence of U6 snRNA. We observe that some
      combinations of 5' splice site and U6 snRNA mutations produce a specific
      synthetic block to the first splicing step. In addition, the U6-G52U allele can
      switch between two competing 5' splice sites harboring different nucleotides
      following the cleavage site. These results indicate that U6 snRNA position 52
      interacts with the first nucleotide of the intron before 5' splice site cleavage.
      Some combinations of U6 snRNA and pre-mRNA mutations also blocked the second
      splicing step, suggesting a role for the corresponding nucleotides in a
      proofreading step before exon ligation. From studies in diverse organisms,
      various functions have been ascribed to the conserved U6 snRNA 47ACAGAG52
      sequence. Our results suggest that these discrepancies might reflect variations
      between different experimental systems and point to an important conserved role
      of this sequence in the splicing reaction.

PMID- 9570317
TI  - Ribosomal release without peptidyl tRNA hydrolysis at translation termination in
      a eukaryotic system.
AB  - A 22-codon upstream open reading frame (uORF2) in the human cytomegalovirus UL4
      transcript leader inhibits downstream translation in cis. Previous studies
      revealed that the peptide product of uORF2 mediates this inhibitory effect by
      interfering with translation termination at its own stop codon. The block at
      termination results both in accumulation of the nascent uORF2 peptide linked to
      tRNA(Pro), the tRNA that decodes the final codon of uORF2, and in stalling of
      ribosomes at the end of uORF2. The stalled ribosomes create a barrier that
      obstructs ribosomal transit to the downstream cistron. In the current studies, we
      further investigated the mechanism of uORF2-mediated translational inhibition by
      assessing the kinetics of uORF2 peptidyl tRNA(Pro) hydrolysis and ribosomal
      release from the uORF2 termination site. Whereas hydrolysis of a mutant,
      noninhibitory uORF2 peptidyl tRNA is nearly complete in less than 1 min,
      hydrolysis of the wild-type peptidyl tRNA is negligible even after 30 min. In
      spite of this remarkably prolonged block to hydrolysis of the uORF2 peptidyl
      tRNA(Pro), most ribosomes are released from the uORF2 termination site within 15
      min. Thus, peptidyl tRNA hydrolysis is not absolutely required for ribosomal
      release in this system. These results suggest that a eukaryotic cellular
      mechanism exists for removing stalled ribosomes from mRNAs in the absence of
      peptidyl tRNA hydrolysis.

PMID- 9570318
TI  - Mutational analysis of the donor substrate binding site of the ribosomal
      peptidyltransferase center.
AB  - Previous experiments have shown that the top of helix 90 of 23S rRNA is highly
      important for the ribosomal peptidyltransferase activity and might be part of the
      donor (P) site. Developing on these studies, mutations in the 23S rRNA at the
      highly conserved positions G2505, G2582, and G2583 were investigated. None of the
      mutations affected assembly, subunit association, or the capacity of tRNA binding
      to A and P sites. A "selective transpeptidation assay" revealed that the
      mutations specifically impaired peptide bond formation. Results with a modified
      "fragment" assay using the minimal donor substrate pA-fMet are consistent with a
      model where the nucleotides psiGG2582 form a binding pocket for C75 of the tRNA.

PMID- 9570319
TI  - The U14 snoRNA is required for 2'-O-methylation of the pre-18S rRNA in Xenopus
      oocytes.
AB  - We have studied the role of the U14 small nucleolar RNA (snoRNA) in pre-rRNA
      methylation and processing in Xenopus oocytes. Depletion of U14 in Xenopus
      oocytes was achieved by co-injecting two nonoverlapping antisense
      oligonucleotides. Focusing on the earliest precursor, depletion experiments
      revealed that the U14 snoRNA is essential for 2'-O-ribose methylation at nt 427
      of the 18S rRNA. Injection of U14-depleted oocytes with specific U14 mutant
      snoRNAs indicated that conserved domain B, but not domain A, of U14 is required
      for the methylation reaction. When the effect of U14 on pre-rRNA processing is
      assayed, we find only modest effects on 18S rRNA levels, and no effect on the
      type or accumulation of 18S precursors, suggesting a role for U14 in a step in
      ribosome biogenesis other than cleavage of the pre-rRNA. Xenopus U14 is,
      therefore, a Box C/D fibrillarin-associated snoRNA that is required for site
      specific 2'-O-ribose methylation of pre-rRNA.

PMID- 9570321
TI  - Utilization of a mammalian cell-based RNA binding assay to characterize the RNA
      binding properties of picornavirus 3C proteinases.
AB  - Using an assay capable of detecting sequence-specific RNA/protein interactions in
      mammalian cells, we demonstrate that the poliovirus and rhinovirus 3C proteinases
      are able to bind structured target RNA sequences derived from their respective 5'
      noncoding regions in vivo. Specific RNA binding by poliovirus 3C was found to be
      dependent on the integrity of stem-loop d of the RNA cloverleaf structure located
      at the 5' end of poliovirus genomic RNA. In contrast, mutation of stem-loop b did
      not prevent this in vivo interaction. However, mutation of stem-loop b, which
      serves as the RNA binding site for a cellular co-factor important for efficient
      poliovirus replication, did significantly attenuate the efficiency of 3C RNA
      binding in vivo and 3CD RNA binding in vitro. This in vivo protein:RNA binding
      assay was also used to identify several residues in 3C that are critical for RNA
      binding, but dispensable for 3C proteinase activity. The mammalian cell-based RNA
      binding assay described in this study may have considerable potential utility in
      the future detection or analysis of in vivo RNA/protein interactions unrelated to
      the 3C/RNA interaction described here.

PMID- 9570320
TI  - ATP is a cofactor of the Upf1 protein that modulates its translation termination
      and RNA binding activities.
AB  - The nonsense-mediated mRNA decay pathway decreases the abundance of mRNAs that
      contain premature termination codons and prevents suppression of nonsense
      alleles. The UPF1 gene in the yeast Saccharomyces cerevisiae was shown to be a
      trans-acting factor in this decay pathway. The Upf1p demonstrates RNA-dependent
      ATPase, RNA helicase, and RNA binding activities. The results presented here
      investigate the binding affinity of the Upf1p for ATP and the consequences of ATP
      binding on its affinity for RNA. The results demonstrate that the Upf1p binds ATP
      in the absence of RNA. Consistent with this result, the TR800AA mutant form of
      the Upf1p still bound ATP, although it does not bind RNA. ATP binding also
      modulates the affinity of Upf1p for RNA. The RNA binding activity of the DE572AA
      mutant form of the Upf1p, which lacks ATPase activity, still bound ATP as
      efficiently as the wild-type Upf1p and destabilized the Upf1p-RNA complex.
      Similarly, ATPgammaS, a nonhydrolyzable analogue of ATP, interacted with Upf1p
      and promoted disassociation of the Upf1p-RNA complex. The conserved lysine
      residue (K436) in the helicase motif Ia in the Upf1p was shown to be critical for
      ATP binding. Taken together, these findings formally prove that ATP can bind
      Upf1p in the absence of RNA and that this interaction has consequences on the
      formation of the Upf1p-RNA complex. Further, the results support the genetic
      evidence indicating that ATP binding is important for the Upf1p to increase the
      translation termination efficiency at a nonsense codon. Based on these findings,
      a model describing how the Upf1p functions in modulating translation and turnover
      and the potential insights into the mechanism of the Upf1p helicase will be
      discussed.

PMID- 9570322
TI  - Tailing and 3'-end labeling of RNA with yeast poly(A) polymerase and various
      nucleotides.
AB  - We have tested conditions for the labeling and tailing the 3'-end of RNAs with
      yeast poly(A) polymerase. Conditions were optimized for addition of NTP, dNTP, or
      ddNTP nucleotides to RNA. ATP, GTP, and UTP were useful for adding homopolymer
      tracts of various lengths. The nonradioactive nucleotides biotin-N6-ATP and
      digoxigenin-11-UTP also were used efficiently.

PMID- 9570323
TI  - Construction of an in vivo-regulated U6 snRNA transcription unit as a tool to
      study U6 function.
AB  - U6 snRNA is the only spliceosomal snRNA transcribed by RNA polymerase III in
      yeast. We have constructed a regulated U6 snRNA transcription unit by introducing
      the binding site for the Escherichia coli lacI repressor protein in the U6 snRNA
      promoter. GAL-induced expression of lacI protein led to a decrease in U6 snRNA
      levels and blocked cell growth. lacI dissociation from the promoter, and
      consequent U6 snRNA transcription, could be induced by addition of IPTG and
      repression of lacI transcription. To test the usefulness of this system in
      studying spliceosomal U6 snRNA function, we conditionally expressed U6 snRNAs
      with a single base substitution in position A51. We demonstrate that expression
      of the U6-A51 mutations confers a strong dominant negative phenotype as shown by
      severe reductions in growth rate. In these strains, splicing of endogenous pre
      mRNAs was blocked before the second step.

PMID- 9570324
TI  - Hexachlorobenzene-induced alterations of rat hepatic microsomal membrane
      function.
AB  - The time and dose-dependent effects of the in vivo administration of
      hexachlorobenzene (HCB), on hepatic microsomal membrane functions, were studied
      in female Wistar rats. Administration of HCB (100 mg/100 g b.w.) resulted in time
      dependent decreases in the activity of two membrane-bound enzymes: 5'nucleotidase
      and Na+/K+ ATPase. HCB was found to cause a significant rise in protein tyrosine
      kinase (PTK) activity during the early stages of intoxication (day 2), followed
      by a significant decrease at 10 days, returning to control levels after 20 days
      of treatment. A stimulatory effect of HCB on in vitro endogenous microsomal
      protein phosphorylation was observed from 2 days of intoxication up to 30 days of
      treatment, with an important stimulation of phosphorylation at 5 days.
      Administration of HCB (100 mg/100 g b.w.) for 10 days caused a 50% reduction in
      epidermal growth factor receptor (EGF-R) ligand binding. The effects of known
      specific inhibitors of protein phosphatases on endogenous protein phosphorylation
      were studied. HCB affected the labelling of several bands, as well as the
      5'nucleotidase and PTK activities, in a dose-dependent manner. In conclusion,
      this study indicated that the in vivo administration of HCB results in a
      significant alteration of membrane function.

PMID- 9570326
TI  - Allylamine and beta-aminopropionitrile induced aortic medial necrosis: mechanisms
      of synergism.
AB  - We have developed a model of aortic smooth muscle necrosis in adult Sprague
      Dawley rats by feeding them two vascular toxins (allylamine HCl, or AA, and beta
      aminopropionitrile, or betaAPN) in concert for 10 days. Either toxin given alone
      does not cause aortic lesions. In order to shed light on the mechanism of the
      synergistic action of these two toxins we fed known modulators of AA or betaAPN
      toxicity to rats concurrently with the two toxins. As modulators we used (a)
      semicarbazide (98 mg/kg/day, given 4 h prior to toxins), a known inhibitor of the
      vascular enzyme SSAO which metabolizes AA; (b) L-cysteine (1.5% in rat chow,
      beginning 3 days prior to toxins), which has been shown to reduce the toxic
      effects of betaAPN; and (c) phenelzine sulphate (3 mg/kg/day, given 4 h prior to
      toxins), an inhibitor of SSAO and potentiator of betaAPN toxicity. Rats were fed
      various combinations of the toxins and modulators by gavage: water (n = 8); (AA,
      100 mg/kg/day) AA + phenelzine (n = 8); AA + semicarbazide (n = 8); AA + L
      cysteine (n = 11); (betaAPN, 1 g/kg/day) betaAPN + phenelzine (n = 8); betaAPN +
      semicarbazide (n = 8); betaAPN + L-cysteine (n = 8); (AA, 100 mg + betaAPN, 1
      g/kg/day) AA + betaAPN + phenelzine (n = 9), AA + betaAPN + semicarbazide (n =
      8); AA + betaAPN + L-cysteine (n = 12); phenelzine (3 mg/kg/day) (n = 4);
      semicarbazide (98 mg/kg/day) (n = 4) and L-cysteine (1.5% in rat chow) (n = 4).
      We found that phenelzine sulphate (a drug previously used in the treatment of
      hypertension) when given with AA reproduced the AA + betaAPN induced aortic
      lesions. Phenelzine + betaAPN caused no lesions, but when combined with AA +
      betaAPN, aortic lesions were intensified and included marked secondary
      degeneration of the vascular wall. Semicarbazide was found to completely obviate
      the vascular toxicity of AA + betaAPN. L-Cysteine feeding markedly decreased the
      incidence and severity of vascular lesions in AA + betaAPN treated rats, but did
      not change the incidence or severity of heart lesions caused by AA alone. These
      data indicate that the synergistic necrotizing toxicity of AA + betaAPN is
      primarily an AA effect. We postulate that some modulating influence of betaAPN
      (or phenelzine) on tissue distribution, metabolism, or detoxification pathways of
      AA increases AA's acute vascular toxicity, whereas semicarbazide offers
      protection by inhibiting the initial deamination of AA to a highly reactive
      aldehyde.

PMID- 9570325
TI  - Formation of zinc protoporphyrin in cultured hepatocytes: effects of
      ferrochelatase inhibition, iron chelation or lead.
AB  - The formation of zinc protoporphyrin in response to lead or iron depletion has
      previously been investigated in erythroid systems. Because of its possible
      metabolic role in non-erythroid tissue, we investigated the formation of zinc
      protoporphyrin in cultured hepatocytes. The effects of lead and inhibitors of
      ferrochelatase, the iron insertion step of heme synthesis, on the conversion of 5
      aminolevulinic acid to zinc protoporphyrin, protoporphyrin and heme were compared
      in rat and chick embryo hepatocyte cultures. In rat cultures, zinc protoporphyrin
      was synthesized enzymatically by ferrochelatase, since N-methylmesoporphyrin, an
      inhibitor of ferrochelatase. caused 40% or greater decreases in both heme and
      zinc protoporphyrin accumulation and markedly stimulated protoporphyrin
      accumulation. In addition, chelation of ferrous iron with 2,2'-dipyridyl
      decreased heme accumulation by 50%, but increased ZPP accumulation by 200%. Zinc
      protoporphyrin formation in chick embryo hepatocytes required the addition of
      zinc as well as 5-aminolevulinic acid and apparently was non-enzymatic, since it
      was not inhibited by N-methylmesoporphyrin nor increased by iron chelation. In
      the presence of 5-aminolevulinic acid, lead had no effect on zinc protoporphyrin,
      protoporphyrin or heme accumulation in chick hepatocytes, but decreased all three
      in rat hepatocytes, with the decrease in protoporphyrin being far greater than
      that of zinc protoporphyrin or heme. These findings indicate that, in contrast to
      the effect of lead in erythroid tissue, it did not specifically increase zinc
      protoporphyrin accumulation or alter iron availability in cultured hepatocytes.

PMID- 9570327
TI  - Cytotoxicity of a series of mono- and di-substituted thiourea in freshly isolated
      rat hepatocytes: a preliminary structure-toxicity relationship study.
AB  - The cytotoxicity of a series of 12 mono- and 4 di-substituted thiourea containing
      compounds in freshly isolated rat hepatocytes was investigated. It was found that
      thiourea toxicity, as evidenced by an increase in LDH-leakage from the cells, was
      accompanied by a depletion of intracellular glutathione (GSH). No increase in
      lipid peroxidation was observed with any of the thiourea. Burimamide and
      thioperamide, thiourea-containing histamine receptor ligands, were also found to
      deplete intracellular GSH. A clear structure-toxicity relationship was uncovered
      among a homologous series of N-phenylalkylthiourea. N-benzylthiourea (BTU) and N
      phenylethylthiourea (PETU) were found to be non-toxic at a concentration of 1 mM,
      while N-phenylpropylthiourea (PPTU) and N-phenylbutylthiourea (PBTU) were found
      to cause significant LDH-leakage from the cells, accompanied by a depletion of
      intracellular GSH. This structure-toxicity relationship was further investigated
      using hepatocytes of differentially induced rats, however, no significantly
      different results were obtained when using hepatocytes of rats induced with
      phenobarbital (PB) or beta-naphthoflavone (BNF). Oxidation of the thiourea moiety
      is thought to be the first step in the bioactivation of thiourea containing
      compounds. The oxidation of thiocholine sulfenic acids, produced by FMO-mediated
      oxidation of the thiourea moiety, was used to determine whether the compounds
      examined are substrates for the FMO enzymes in rat liver. No clear relationship
      was found between cytotoxicity of the mono-substituted thiourea and lipophilicity
      of the N-substituent, nor with the FMO-mediated oxidation of the thionosulfur
      atom of the mono-substituted thiourea. It is concluded from this study, that
      thiourea toxicity in rat hepatocytes is structure-dependent and manifests itself
      as LDH-leakage and as a depletion of intracellular non-protein sulfhydryls,
      notably GSH, most likely followed by alkylation of vital macromolecular
      structures.

PMID- 9570328
TI  - Paracetamol hepatotoxicity in metallothionein-null mice.
AB  - The role of metallothionein (MT) in protecting the liver against paracetamol
      (PCT) toxicity was investigated in vivo and in vitro in mice lacking expression
      of MT-1 and MT-2 genes (MT -/-). In the fed, glycogen replete state,
      hepatotoxicity (PCT 300 mg/kg i.p.) at 6 h was significantly greater in MT -/-
      than MT +/+ mice. Plasma lactate dehydrogenase (LD) and alanine aminotransferase
      (ALT) were 5- and 13-fold greater respectively than in MT +/+ mice. Liver
      glycogen, glucose and zinc levels were significantly lower in MT -/- mice at this
      time. In contrast, hepatotoxicity (PCT 135 mg/kg i.p.) at 6 h was similar in both
      MT +/+ and MT -/- mice fasted 24 h, despite a doubling in liver MT in MT +/+
      mice. No differences were found between MT -/- and MT +/+ mice in cytochrome P450
      activity. Liver glutathione levels were the same in both groups of mice prior to
      fasting and were decreased to a similar extent (55-65%) following PCT treatment.
      Investigation of lower PCT doses (< or = 120 mg/kg) in fasted mice over 24 h
      demonstrated a greater susceptibility in female MT -/- mice with plasma LD, 2.4
      fold and ALT, 7.5-fold greater than in MT +/+ mice at 120 mg/kg PCT. In male MT 
      /- mice, there was only a trend towards greater susceptibility at 110 mg/kg PCT
      compared to male MT +/+ mice, and at 120 mg/kg, both male genotypes were equally
      affected. Investigations with cultured hepatocytes supported the in vivo findings
      in that there was a trend towards greater toxicity (PCT at 1 and 5 mM for 24 h)
      in hepatocytes from fed MT -/- mice, with the difference diminished in
      association with greater hepatotoxicity in hepatocytes from fasted mice. Use of
      dexamethasone (Dex) to increase MT in the MT +/+ mouse hepatocytes protected from
      PCT toxicity. Zn alone was not protective. Zn plus Dex offered no protection
      despite higher MT levels. Generation of apo-MT with Dex may offer more protection
      than Zn-MT. In conclusion, MT -/- mice were more susceptible than MT +/+ mice to
      PCT toxicity in the fed state, but the increased susceptibility was much smaller,
      but still significant, when the effects of glycogen were minimised by fasting.

PMID- 9570329
TI  - Effect of pentachlorophenol on immune function.
AB  - The organochlorine compound, pentachlorophenol, was evaluated for effects on
      immune system function in male Fisher 344 rats. Pentachlorophenol was prepared in
      an olive oil vehicle and was administered by oral gavage twice weekly for 28 days
      at a dose of 2.0 mg/kg per treatment. Exposure to pentachlorophenol increased
      body weight gains (P=0.024) during the treatment period. Liver (P=0.034) and
      kidney (P=0.012) body weight ratios were also increased. Pentachlorophenol
      exposure enhanced T-lymphocyte blastogenesis induced by concanavalin A (Con
      A)(P=0.0001) and phytohemagglutinin (PHA)(P=0.048) evaluated using stimulation
      indices. Corresponding B-lymphocyte blastogenesis induced by
      lipopolysaccharide/dextran (LPS/dex)(P=0.0034) was also enhanced by
      pentachlorophenol exposure. Pentachlorophenol suppressed the antibody response
      against sheep red blood cells (SRBCs) by 39% when the response was expressed per
      viable spleen cell (P=0.006). This suppression was not evident when the response
      was expressed per spleen (P=0.22), suggesting that a compensatory mechanism or
      extramedullary splenic hemopoiesis was occurring minimizing the overall impact on
      humoral immunity. The enhanced B- and T-lymphocyte blastogenesis may also reflect
      compensatory or hemopoietic activity. Pentachlorophenol exposure had no effect on
      peritoneal macrophage phagocytosis (P=0.31) or lymphocyte cell surface antigen
      expression. The observed alterations in lymphocyte blastogenesis and humoral
      immunity subsequent to pentachlorophenol exposure do not appear to be associated
      with phagocytosis or lymphocyte cell surface antigen expression.

PMID- 9570330
TI  - A modified murine local lymph node assay for the differentiation of contact
      photoallergy from phototoxicity by analysis of cytokine expression in skin
      draining lymph node cells.
AB  - Since predictive differentiation of photoallergenic from phototoxic reactions,
      induced by low molecular weight compounds, represents a current problem, we tried
      to improve the differentiation between the two reactions by using a modified
      protocol of the local lymph node assay (LLNA). Briefly, groups of female BALB/c
      mice received compound solution or vehicle alone on the dorsum of both ears on 3
      consecutive days. Immediately after compound application indicated groups of mice
      were exposed to a UVA light-dose of 10 J/cm2. Auricular lymph nodes draining the
      ear tissue were excised 24 h following the last exposure. Evaluation consisted of
      assessing lymph node weights and cell counts to monitor organ hyperplasia and in
      vivo-proliferative events following substance application. Furthermore, we
      analysed cytokine gene transcription in freshly prepared lymph node cells (LNC)
      and the cytokine release in vitro by restimulated CD4+ T-cells and antigen
      presenting cells (APC), both purified from the skin-draining lymph nodes. Both
      contact (photo) allergenic (oxazolone and tetrachlorosalicylanilide) and
      phototoxic substances (8-methoxypsoralen and acridine) caused a dose dependent
      increase in lymph node weights and cell counts pointing to an inflammatory
      process in the lymph nodes. Analysis of cytokine gene transcription ex vivo and
      cytokine release in vitro revealed that during the induction phase of contact
      (photo) allergy CD4+ T-cells produced IL-2 and IFN-gamma as well as IL-4 and IL
      10, whereas IL-6 was derived from APC. In contrast, phototoxic reactions caused
      only an upregulation of IL-2 and IFN-gamma. Furthermore, we demonstrate that the
      release of IL-4 and IL-10 by CD4+ T-cells was clearly increased, whereas IL-6 and
      IFN-gamma expression was reduced or not changed following a challenge with
      contact (photo) allergens revealing an allergy-indicative shift in cytokine
      expression. In conclusion, our results show that contact photoallergenic
      reactions could be differentiated from phototoxic events by analysis of LNC
      cytokine expression patterns.

PMID- 9570331
TI  - Nephrotoxicity studies of the immunosuppressants tacrolimus (FK506) and ascomycin
      in rat models.
AB  - The nephrotoxic potential of ascomycin, the C21-ethyl analogue of FK506, was
      defined and ways explored to enhance its detection. After 14-day dosing in the
      Fischer-344 rat, FK506 and ascomycin reduced creatinine clearance by >50% at
      doses of 1 and 3 mg/kg, i.p., respectively. Ascomycin also had a 3-fold lower
      immunosuppressive potency in a popliteal lymph node hyperplasia assay, resulting
      in an equivalent therapeutic index consistent with a common mechanistic
      dependence on calcineurin inhibition. Renal impairment with different routes of
      administration was correlated with pharmacokinetics. Sensitivity of detection was
      not adequate with shorter dosing durations in rats with unilateral nephrectomy or
      in mice using a cytochrome P-450 inhibitor, SKF-525A. In 14-day studies,
      nephrotoxicity was not induced by continuous i.p. infusion of ascomycin at 10
      mg/kg/day or daily oral administration (up to 50 mg/kg/day) in rats on a normal
      diet, nor by continuous i.v. infusion (up to 6 mg/kg/day) in rats on a low salt
      diet to enhance susceptibility. The lack of toxicity at high oral doses of FK506
      or ascomycin, and the finding of non-linear oral pharmacokinetics of ascomycin
      show that this drug class has an oral absorption ceiling. The negative results
      with continuous infusion suggest that ascomycin nephrotoxicity is governed by
      peak drug levels. In addition to defining ways to meaningfully compare the
      nephrotoxic potential of FK506 derivatives, these results have implications for
      overall safety assessment and improved clinical use.

PMID- 9570332
TI  - Report of validation study of assessment of direct immunotoxicity in the rat. The
      ICICIS Group Investigators. International Collaborative Immunotoxicity Study.
AB  - The International Collaborative Immunotoxicity Study (ICICIS) was established in
      1986 as a joint activity of the International Programme on Chemical Safety (a
      cooperative programme of the United Nations Environment Programme, the
      International Labour Office and the World Health Organization), the Commission of
      the European Union and the United Kingdom Department of Health. The objectives
      were to examine whether various experimental techniques could be used in the rat
      to indicate toxic effects on the immune system, and so to suggest their possible
      value as general indicators of immunotoxicity. For this purpose scientists in a
      number of laboratories in different countries agreed to do joint studies, first
      of azathioprine (AZA) and then of cyclosporin A (CYA), as potent
      immunosuppressive compounds. The general experimental procedures and the detailed
      techniques employed were selected to explore whether the limited pathological
      investigations in the conventional 28-day subacute toxicity test in the rat
      (OECD, 1995), or 'Enhanced Pathology' tests (weight determination and examination
      of additional lymphoid organs and application of structured assessment and
      semiquantitative grading of changes in the principal compartments of lymphoid
      tissues) would suffice to indicate ('flag') the occurrence of immunotoxicity due
      to a chemical, or whether specific tests of immune function would be required.
      When the second chemical, CYA, was studied, standardisation of the protocol for
      the test, and of all the investigations, and prior training of the toxicological
      pathologists in the structured assessment scheme, were shown to greatly reduce
      interlaboratory variation in the results. The initial investigation of AZA had
      shown that the indicative power of the experiments had been diminished by the use
      of diverse experimental procedures. The studies were done as toxicity tests, in
      which three dose levels, including the maximum tolerated dose, and a vehicle
      control group were employed. The prime objective was to detect any immunotoxic
      effect of the test compound. It was shown that the limited, basic 'Pathology'
      investigations specified in Guideline 407 (OECD, 1981) were not able to reveal
      the effects on the immune system of AZA and CYA, but that several of the
      additional 'Enhanced Pathology' investigations did so. Of the immune function
      assays, the most reliable and useful was the 'Antibody Forming Cell' technique.
      Other immunological evaluations, such as examination of proliferation induced by
      selected mitogens and NK cell assay, showed promise. The methods employed have
      the potential to reveal an 'immunotoxic' effect, without necessarily indicating
      its mechanism, although the changes in different lymphoid compartments can afford
      a valuable guide to the detailed nature of the toxic action on the immune system.
      Function tests, being inherently quantitative in nature may well suggest the
      nature or mechanism of any effect seen, in addition to indicating the occurrence
      of the effect. However, they may be less convenient to do as part of a routine
      toxicity test. Overall, the work in ICICIS has shown that the immunotoxic actions
      of two chemicals were detectable within a 28-day subacute oral toxicity test in
      the rat, provided that the conventional laboratory procedures were extended to
      include extra investigations. Both additional selected pathology investigations
      and immune function tests 'flagged' the immunotoxicity.

PMID- 9570333
TI  - Modulation of nitric oxide, hydrogen peroxide and cytokine production in a clonal
      macrophage model by the trichothecene vomitoxin (deoxynivalenol).
AB  - Characterization of how vomitoxin (VT) and other trichothecenes affect macrophage
      regulatory and effector function may contribute to improved understanding of
      mechanisms by which these mycotoxins impact the immune system. The RAW 264.7
      murine cell line was used as a macrophage model to assess effects of the VT on
      proliferation and the production of nitric oxide (NO), hydrogen peroxide (H2O2)
      and cytokines. Using the MTT cleavage assay, VT at concentrations of 50 ng/ml or
      higher was found to significantly decrease proliferation and viability of RAW
      264.7 cells without stimulation or with stimulation by lipopolysaccharide (LPS)
      or interferon (IFN)-gamma. In the absence of an activation agent, VT (25-250
      ng/ml) had negligible effects on the production of NO, H2O2, and cytokines. Upon
      activation with LPS at concentrations of 10 to 100 ng/ml, VT at 25-100 ng/ml
      markedly enhanced production of H2O2 but was inhibitory at 250 ng/ml. VT
      enhancement of H2O2 production was observed as early as 12 h after LPS
      stimulation. When IFN-gamma was used as the stimulant, VT (25-250 ng/ml) delayed
      peak H2O2 production. VT (25-250 ng/ml) also markedly decreased NO production in
      cells activated with LPS or IFN-gamma. Interestingly, VT superinduced TNF-alpha
      and IL-6 production in LPS-stimulated cells and also elevated TNF-alpha in IFN
      gamma stimulated cells. These results suggest that VT can selectively and
      concurrently upregulate or downregulate critical functions associated with
      activated macrophages.

PMID- 9570334
TI  - Mercury-induced autoimmunity in Brown Norway rats: kinetics of changes in RT6+ T
      lymphocytes correlated with IgG isotypes of circulating autoantibodies to laminin
      1.
AB  - Repeated exposure to mercury causes various autoimmune effects in rats of the
      Brown Norway (BN) strain. Previous studies from our laboratory have shown that on
      day 15 of HgCl2 treatment BN rats exhibit a relative decrease in RT6.2+ T cells.
      At the same time, they produce high levels of autoantibodies to renal antigens
      and experience a membranous glomerulonephropathy. In contrast, Lewis (LEW) rats
      are resistant to autoimmunity caused by mercury and do not demonstrate a decrease
      in RT6+ cells after administration of HgCl2. In the present paper we provide
      novel information on the correlation between changes in RT6.2+ lymph node T cells
      and the production of autoantibodies to laminin 1, obtained by detailed kinetic
      studies of HgCl2-treated BN rats. We have confirmed a decrease in the percentage
      of RT6.2+ lymphocytes on day 15 of mercury treatment, despite a significant
      increase in the number of peripheral lymphocytes. No such changes were observed
      in LEW rats. We have determined that on day 15 the percentage decrease in RT6+
      cells is evident in both RT6.2+CD4+ and RT6.2+CD8+ T cell subsets. Kinetic
      studies demonstrated that significant changes in the percentage of RT6.2+ cells
      are first observed by day 8 and continue through days 11 and 15. We have also
      observed a significant percent decrease in CD4+ T lymphocytes as well as an
      increase in CD4-CD8- cells. The dramatic increase in the percentage of these
      double negative cells at the level of peripheral lymphoid tissues does not appear
      to be due to higher thymic output, since there was a decrease in the percentage
      of TCR+Thy1+ cells, a phenotype that is associated with recent thymic emigrants.
      Finally, we have demonstrated that 100% of HgCl2-treated BN rats had circulating
      antibodies that reacted with both mouse and rat laminin 1, i.e. are
      autoantibodies to laminin 1. These autoantibodies were predominantly of the IgG1
      and IgG2a isotype, possibly as the result of a polarized autoimmune response
      driven by Type 2 cytokines. A kinetic investigation showed that significant
      levels of IgG1 and IgG2a autoantibodies to laminin 1 were first presentin the
      circulation by day 11. The inverse correlation between levels of RT6.2+ T
      lymphocytes and autoantibodies to laminin 1 suggests that mercury may induce
      autoimmune responses in BN rats by its effects on these immunoregulatory cells.

PMID- 9570335
TI  - Medium chain fatty acid metabolism and energy expenditure: obesity treatment
      implications.
AB  - Fatty acids undergo different metabolic fates depending on their chain length and
      degree of saturation. The purpose of this review is to examine the metabolic
      handling of medium chain fatty acids (MCFA) with specific reference to
      intermediary metabolism and postprandial and total energy expenditure. The
      metabolic discrimination between varying fatty acids begins in the GI tract, with
      MCFA being absorbed more efficiently than long chain fatty acids (LFCA).
      Subsequently, MCFA are transported in the portal blood directly to the liver,
      unlike LCFA which are incorporated into chylomicrons and transported through
      lymph. These structure based differences continue through the processes of fat
      utilization; MCFA enter the mitochondria independently of the carnitine transport
      system and undergo preferential oxidation. Variations in ketogenic and lipogenic
      capacity also exist. Such metabolic discrimination is supported by data in
      animals and humans showing increases in postprandial energy expenditure after
      short term feeding with MCFA. In long term MCFA feeding in animals, weight
      accretion has been attenuated. These differences in metabolic handling of MCFA
      versus LCFA are considered with the conclusion that MCFA hold potential as weight
      loss agents.

PMID- 9570336
TI  - Pancreatic polypeptide stimulates rat adrenal glucocorticoid secretion by
      activating the adenylate cyclase-dependent signaling pathway.
AB  - Pancreatic polypeptide (PP) concentration-dependently raised basal corticosterone
      and cyclic-AMP production of dispersed rat zona fasciculata/reticularis
      adrenocortical cells, maximal effective concentration being 10(-7) M. 10(-7) M PP
      also significantly enhanced submaximally (10[-12]/10[-11] M), but not maximally
      (10[-9]/10[-8] M) ACTH-stimulated corticosterone and cyclic-AMP release.
      Corticosterone responses to PP were abolished by the specific protein kinase A
      (PKA) antagonist H-89 (10[-5] M). The selective ACTH-receptor antagonist
      corticotropin-inhibiting peptide (10[-6] M) annulled corticosterone response to
      10(-9) M ACTH, but not to 10(-7) M PP. Collectively, our present findings
      indicate that PP stimulates glucocorticoid secretion of rat adrenal glands,
      acting through specific receptors coupled, like those of ACTH, with the adenylate
      cyclase/PKA-dependent signaling pathway.

PMID- 9570337
TI  - Distribution and characterization of anandamide amidohydrolase in mouse brain and
      liver.
AB  - Anandamide (N-Arachidonoylethanolamine) amidohydrolase catalyzing hydrolysis of
      anandamide was characterized in mice. The enzymatic activity was highest in the
      liver, followed by the brain and testis. Negligible activity was found in heart,
      lung and spleen. The activity in brain and liver was mainly localized in the
      microsomal fractions. Kinetic experiments demonstrated that Km (microM) and Vmax
      (nmol/min/mg protein) for the brain microsomes were 9.3 and 2.58, respectively,
      while those for the hepatic microsomes were 180 and 18.9, respectively. The
      activity in the microsomes from the liver and brain was markedly inhibited by
      Cu2+, Hg2+, Se4+, phenylmethylsulfonylfluoride and sodium dodecylsulfate. Brain
      but not hepatic microsomal enzyme activity was inhibited by delta9
      tetrahydrocannabinol, cannabidiol and cannabinol. Kinetic parameters demonstrated
      that the inhibition by the cannabinoids was competitive in nature. Relatively
      high distribution of the enzyme activity in brain suggests an importance of the
      enzyme in the central nervous system to regulate the neuromodulatory fatty-acid
      amides.

PMID- 9570338
TI  - Species differences in the disposition of propranolol prodrugs derived from
      hydrolase activity in intestinal mucosa.
AB  - The bioavailability of propranolol (PL) after oral administration of ester-type
      prodrug was compared in rat and dog, and the possible reason for species
      difference was investigated. In dog, the oral bioavailability of PL was enhanced
      by the use of prodrug due to saturation of metabolism of PL. In contrast, high
      (10 mg/kg) and low (2.5 mg/kg) doses of butyryl PL and isovaleryl PL failed to
      improve oral bioavailability of PL in rats. The hydrolase activities for prodrugs
      in rat liver were lower than those of dog (by 4-12-fold), but those of rat
      intestinal mucosa were significantly higher than those of dog (50-260-fold).
      Although it is clear from the in vitro hydrolysis using subcellular fractions
      that the rapid hydrolysis in intestinal mucosa was mainly due to cytosolic
      components, the brush-border membrane vesicle in rat intestine also showed
      hydrolase activity for both prodrugs. In situ absorption experiment in rat
      revealed an improvement in the apparent absorption rate of PL as the result of
      prodrug use (1.3-fold) and the nearly complete hydrolysis of isovaleryl PL during
      intestinal absorption, which is a slower hydrolyzed prodrug than butyryl PL in
      intestinal mucosa and liver. The defects for enhancing oral bioavailability in
      rats appears to be based on an unsaturation of metabolism for PL, which is
      derived from a decrease in PL concentration in hepatocytes, owing to rapid
      hydrolysis of the prodrug in intestinal mucosa and slow hydrolysis of the prodrug
      in liver. Furthermore, human intestinal mucosa showed a surprisingly high
      hydrolase activity in microsomes. Therefore, the oral bioavailability of PL after
      administration of prodrugs might be not significantly improved in human.

PMID- 9570339
TI  - T lymphopenia in obese diabetic (db/db) mice is non-selective and thymus
      independent.
AB  - Although C57BL/KsJ db/db mice, an animal model of non-insulin-dependent diabetes
      mellitus (NIDDM), develop T lymphopenia in association with the progression of
      NIDDM, the T lymphopenia has not been fully investigated. In this study, to
      elucidate how and why T lymphopenia develops in db/db mice, T-lymphocyte subsets
      in spleen and thymus were longitudinally examined by flow cytometry and the
      effects of thymectomy and dietary restriction on the development of T lymphopenia
      were evaluated. After 8 weeks of age, when obese diabetes progresses, T
      lymphopenia in both spleen and thymus developed and all T-lymphocyte subsets
      examined were similarly reduced compared to lean (-/X) littermates, indicating
      non-selective T lymphopenia in db/db mice. Thymectomy performed at 5 wk of age,
      when neither T lymphopenia nor NIDDM yet presents, had no significant effect on
      the development of T lymphopenia. Furthermore, pair feeding until 30 weeks of age
      produced normal body weight and normoglycemia with still marked hyperinsulinemia,
      but failed to correct T lymphopenia in db/db mice. In conclusion, our results
      suggest that T lymphopenia may develop non-selectively and independently of
      either thymic dysfunction or obese diabetes in db/db mice.

PMID- 9570340
TI  - Effect of the opioid methionine enkephalinamide on signal transduction in human T
      lymphocytes.
AB  - T cell receptor (TCR/CD3) induced fluctuations in intracellular free ionizied
      calcium, [Ca2+]i, was analysed in the human T leukemia cell clone, Jurkat,
      cultured in the presence of the opioid methionine enkephalinamide (Met-Enk) in
      titrated concentrations (10[-7] to 10[-15] M) or saline (PBS). In the majority of
      individual experiments, the activation-induced fluctuations in [Ca2+]i were
      similar in cells cultured in the presence of Met-Enk and PBS, respectively.
      However, when all the experimental data from 101 separate TCR/CD3-activation
      experiments with Met-Enk were compared with the 67 separate control experiments,
      we found that a fraction (20-40%) of the individual sets of Met-Enk experiments
      responded significantly different when compared to PBS-controls. In this fraction
      of experiments the increase in [Ca2+]i after ligation of the TCR/CD3 complex was
      extremely slow compared to controls. Moreover, the levels of [Ca2+]i in this
      particular fraction were lower than control levels prior to ligation of the
      TCR/CD3 complex. The data support the idea that signal transduction in T cells
      can be influenced by endogenous opioid. The data therefore give credit to the
      evolving hypothesis of a functional relationship between the neuroendocrine
      system and the immune system.

PMID- 9570341
TI  - Evidence for the involvement of the hydroxyl radical in the pathogenesis of
      excessive connective tissue proliferation in patients with tumor-endoprostheses.
AB  - Extensive proliferation of connective tissue around Vitallium implants can be
      observed in young patients who had limb salvage for primary malignant bone
      tumors. The underlying mechanism of excess proliferation and collagen
      accumulation is not known. We were therefore interested to show whether the alloy
      of the implant induced proliferation of fibroblasts in vitro, acted by a
      cytotoxic mechanism or generated free radical cross linking of collagen with
      subsequent accumulation. In vitro tests for proliferation and cytotoxicity using
      the implant material which consists of a series of transition metals, ruled out a
      proliferation-inducing or cytotoxic effect of the implant. Determination of ortho
      tyrosine (OT), a marker for hydroxyl radical attack on phenylalanine, in the
      proliferating tissues surrounding the implants revealed significantly higher
      aromatic hydroxylation in the vitallium surrounding tissue correlating with
      tissue collagen content (r = 0.86, p < 0.01). Based upon the findings of
      increased OT and the presence of higher molecular weight bands on SDS-PAGE,
      representing more cross linked collagen, we suggest that hydroxyl radical attack
      lead to free radical mediated cross linking of collagen with subsequent collagen
      accumulation, as collagen cross-linked to a higher degree is less susceptible to
      proteolytic degradation.The hydroxyl radical attack seems to having been
      generated by the many transitional metals of the vitallium-alloy.

PMID- 9570342
TI  - Alterations of biological parameters in mice chronically exposed to low-frequency
      (50 Hz) electromagnetic fields.
AB  - In an experimental study we measured changes in hematological, biochemical and
      cortisol parameters in 6-week-old Swiss mice continuously exposed to ELF
      generated by a transformer station and high current bus bars. Mean daily exposure
      of 5.0 microT was maintained for 350 days. Hematological parameters were compared
      to those of control mice (n=12) exposed to a field level lower than 0.1 microT.
      Serum biochemical parameters (sodium, potassium, chloride, calcium, magnesium,
      phosphorus, amylase, creatine phosphokinase, and lactate dehydrogenase) were
      measured after 28 days of exposure and serum cortisol after 90 and 190 days.
      Granulocyte/macrophage colony-forming cells (GM-CFC) were counted at the end of
      the 350-day exposure. On day 20, exposed animals showed a significant decrease in
      leukocyte, erythrocyte, lymphocyte and monocyte counts and in hemoglobin and
      hematocrit values, while MCV increased. On days 43 and 63 no significant
      difference was observed in leukocyte and erythrocyte values, as if hemopoiesis
      had recovered. On day 90, a significant fall in the leukocyte, polynuclear
      neutrophil and eosinophil counts was observed in the exposed animals. No
      significant difference was noted in the biochemical parameters studied. On day
      190, exposed animals had neutropenia and a decrease in the cortisol value. On day
      350, no significant difference in hematological parameters was noted. Individual
      differences in sensitivity were observed, as 8 mice in the exposed group showed a
      significant decrease in the leukocyte, polymorphonuclear neutrophil and GM-CFC
      counts, while in two mice there was a significant increase in these same values
      compared to those unexposed mice.

PMID- 9570343
TI  - [125I-Tyr1]biphalin binding to opioid receptors of rat brain and NG108-15 cell
      membranes.
AB  - Mono iodinated analogues of biphalin [(Tyr-D-Ala-Gly-Phe-NH-)2], both
      nonradioactive [I-Tyr1]biphalin and radioactive [125I-Tyr1]biphalin have been
      synthesized. The radioligand binding profiles of these compounds for two types of
      tissues, rat brain membranes, and NG108-15 cell membranes were identical to the
      parent biphalin. This is additional evidence for the hypothesis that biphalin
      behaves like a monomeric ligand and that only one intact tyrosine is necessary
      for high biological activity. The second tyrosine could be used for successful
      radioiodination which may greatly simplify biochemical and pharmacological
      studies of biphalin. The results of receptor binding studies show that the
      binding of both biphalin and [I-Tyr1]biphalin to the delta and mu opioid
      receptors are not independent. [125I-Tyr1]Biphalin binds to delta receptors as
      shown in NG108-15 cell membranes. Nevertheless, [125I]biphalin binding to delta
      receptors in rat brain membranes was hardly evident and mu receptor binding
      predominated or at least was much more readily detectable in this preparation.

PMID- 9570344
TI  - Counteraction of retinoic acid and 1,25-dihydroxyvitamin D3 on up-regulation of
      adipocyte differentiation with PPARgamma ligand, an antidiabetic
      thiazolidinedione, in 3T3-L1 cells.
AB  - Retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3) inhibited
      adipocyte differentiation of 3T3-L1 preadipocytes in the presence of
      thiazolidinedione, a specific ligand for peroxisome proliferator-activated
      receptory (PPARgamma). These fat-soluble vitamins repressed the up-regulated
      protein expression of PPARgamma2 during the first 40 hours of initiation of 3T3
      L1 preadipocyte differentiation. Compared with RA, 1,25 (OH)2 D3 inhibited
      PPARgamma2 expression more effectively and caused concomitantly a greater
      inhibition of adipocyte differentiation. These results suggest that the
      inhibitory action of adipocyte differentiation by RA or 1,25 (OH)2 D3 is
      exhibited through direct repression of the expression of PPARgamma2 protein, even
      in the presence of its ligand. They also raise the intriguing possibility that
      attenuation or amplification of the pharmacological effects of thiazolidinedione
      that are dependent on PPARgamma in adipose cells is caused by alteration of the
      levels of these fat-soluble vitamins.

PMID- 9570345
TI  - Subsensitivity to mitochondrial diazepam binding inhibitor receptor agonist FGIN
      1-27-induced antiseizure effect in diazepam-withdrawn mice.
AB  - We investigated the role of the mitochondrial diazepam binding inhibitor receptor
      (MDR) in diazepam-withdrawal seizure. In chronically vehicle-treated mice, the
      potent and selective MDR agonist FGIN-1-27 (N,N-di-n-hexyl 2-(4
      fluorophenyl)indole-3-acetamide: 30 microg/mouse, i.c.v.) markedly increased the
      threshold for pentylenetetrazole (PTZ)-induced seizure. The antiseizure effect of
      FGIN-1-27 was blocked by pretreatment with the selective MDR antagonist PK11195
      (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxa mide). In
      chronically diazepam-treated mice, the seizure threshold of PTZ was decreased
      during diazepam withdrawal, indicating withdrawal hyperexcitability.
      Interestingly, FGIN-1-27 (30 microg/mouse, i.c.v.) failed to increase the seizure
      threshold of PTZ in diazepam-withdrawn mice, in contrast to its effect in
      chronically vehicle-treated mice. These findings suggest that the sensitivity of
      MDR-mediated pathways in the brain may be decreased during diazepam withdrawal.

PMID- 9570346
TI  - The genetic variant A of human alpha 1-acid glycoprotein limits the blood to
      brain transfer of drugs it binds.
AB  - The objective of this work was to check the effects of alpha-1 acid glycoprotein
      (AAG) and of its components, A and F1/S genetic variants, on the brain transfer
      of drugs they bind in plasma. The relevant extractions of six basic drugs, highly
      bound to AAG, were measured. We chose three drugs selectively bound to the A
      variant, disopyramide, imipramine and methadone, one drug mainly bound to the
      mixture F1/S, mifepristone, and two drugs which were simultaneously bound to the
      variant A and the mixture F1/S, propranolol and chlorpromazine. Their brain
      extraction were investigated in rats using the carotid injection technique and
      the capillary depletion method. Injected drugs were dissolved either in buffer,
      either in native AAG containing the three variants (A, F1 and S), either in
      variant A or in variant F1/S solutions. Brain extractions of disopyramide,
      imipramine and methadone were significantly reduced by native AAG and by variant
      A. Drug's plasma retention was related to their preferential and almost exclusive
      binding to A variant, both of them exhibiting the same decrease in brain transfer
      as compared to a buffered solution. At the opposite, there were no significative
      differences between the extraction either in buffer, either in AAG or in F1/S
      solutions, of drugs both bound to A variant and F1/S mixture (chlorpromazine and
      propranolol) or to the F1/S mixture (mifepristone). In serum, the retentional
      effect of the A variant on the extraction of disopyramide and imipramine was
      counteracted by the presence of albumin and lipoproteins, which simultaneously
      bind these two drugs at a high extent and act as permissive binders. We conclude
      that AAG binding decreases brain drug transfer when the A variant is mainly and
      almost exclusively involved in the binding. On the contrary, the entire fraction
      of the tested drugs when bound exclusively or partly to the mixture F1/S is
      available for transfer into the brain.

PMID- 9570347
TI  - Mutation analysis of the BRCA2 gene in breast/ovarian cancer Spanish families:
      identification of two new mutations.
AB  - The recently isolated gene BRCA2 is responsible for about 45% of familial breast
      cancer and the majority of male breast cancer families. We have screened 12 high
      risk breast/ovarian Spanish families for mutations in BRCA2, using SSCP followed
      by direct sequencing. We have found mutations in four of our 12 families (33.3%),
      including two with male breast cancer. Three of the mutations were frameshift and
      one was a missense. Two of the mutations have been previously published and two
      are new mutations.

PMID- 9570348
TI  - The role of angiogenesis, laminin and CD44 expression in metastatic behavior of
      early-stage low-grade invasive breast carcinomas.
AB  - To investigate the role of tumor angiogenesis, laminin and CD44 expression in
      metastatic potential of breast cancers, 35 early-stage (T1) and/or low-grade
      (grade 1) invasive breast carcinomas including 18 metastasizing and 17 non
      metastasizing cases were analyzed in the present study. Angiogenesis was assessed
      by a stereologic method after immunohistochemical staining of vascular
      endothelium for factor VIII. The quantification of the tumor vascularization was
      based on the vascular surface density (VSD) and the microvessel number (NVES).
      The expressions of laminin and CD44 were evaluated by scoring the intensity and
      distribution of the immunostaining. The assessment of NVES and VSD resulted in a
      statistically significant difference between the two groups (P < 0.05,
      independent-samples t-test). In the breast cancers with metastatic spread, NVES
      was found to be 16.0+/-2.9 mm(-2) whereas it was 8.1+/-0.7 mm(-2) in the
      metastasizing group. VSD was found to be 59.0+/-12.6 mm(-1) in the metastasizing
      group and was significantly lower in the non-metastasizing group (33.8+/-2.6 mm[
      1]). Immunohistochemistry exhibited strongly positive staining for CD44 in 22% of
      the breast cancers with metastasis, while 65% of the non-metastasizing cases were
      found to be negative. The statistical analysis also resulted in a significant
      difference (P = 0.034, chi2 test). However, the immunohistochemical staining for
      laminin did not yield any significant difference (P = 0.347, chi2 test).
      Approximately half of the cases being either metastasizing or non-metastasizing
      stained weakly positive for laminin. We concluded that angiogenesis and CD44
      expression in breast cancers correlated significantly with lymph node or distant
      metastasis. However, the immunodetection of laminin expression in our study did
      not help to evaluate its role in the metastatic potential of breast cancers. We
      concluded that vascular parameters, such as an increase in microvessel number,
      and CD44 expression might be useful prognostic indicators of metastasis in breast
      cancer.

PMID- 9570349
TI  - Enhancement and phenotypic modulation of N-nitrosomorpholine-induced
      hepatocarcinogenesis by dehydroepiandrosterone.
AB  - Hepatocarcinogenesis was induced in male and female rats by continuous
      administration of the adrenal steroid dehydroepiandrosterone (DHEA; 0.6% in the
      diet) with and without previous treatment with N-nitrosomorpholine (NNM; 120 mg/l
      drinking water for 7 weeks). DHEA treatment alone resulted in hepatocellular
      adenomas (HCA) and carcinomas (HCC) after 72-84 weeks, the incidence of both
      benign and malignant neoplasms being higher in females than in males. After DHEA
      administration for up to 32 weeks subsequent to NNM, the incidence of HCA and HCC
      was significantly higher (HCA, 42%; HCC, 42%) than after NNM alone (HCA, 33%;
      HCC, 28%). While total tumor incidence was similar in male (63%) and female (60%)
      rats after NNM treatment alone, it was higher in females (87%) than in males
      (80%) after NNM/DHEA treatment. The difference between the genders was mainly due
      to the higher incidence of HCC in females. Morphometric analysis of preneoplastic
      foci of altered hepatocytes (FAH) yielded that DHEA treatment did not increase
      the average total number of FAH induced by NNM, but caused a modulation of the
      phenotype of FAH from the glycogenotic/basophilic to the amphophilic cell
      lineage. The results confirm that DHEA acts as a hepatocarcinogen and show for
      the first time that it enhances NNM-induced hepatocarcinogenesis in rats.

PMID- 9570350
TI  - Expression of p53 protein in rat colon cancer cell lines transfected with Rous
      sarcoma virus-33.
AB  - Expression of the cytoplasmic soluble form of p53 protein in the different rat
      colon cancer cell lines transfected and non-transfected with Rous sarcoma virus
      33 was studied. Concentrations of the p53 protein were detected by commonly used
      immunochemical methods after its isolation by affinity chromatography columns
      with the gel fiberglass membranes. The main component of tumor-associated
      antigens (TAA) eluted from virus-transfected cells was the 53 kDa protein in its
      cytoplasmic soluble fraction. The non-virogenic colon cancer cells contain a few
      proteins and concentration of 53 kDa protein was low. Western immunoblotting
      revealed that the 53 kDa protein isolated from the cell lyzates studied was
      distinctly recognized by the p53 MAb. ELISA showed that its concentration was
      markedly higher in the lyzate obtained from the highly virogenic and tumorigenic
      R9 cell line compared with the non-virogenic cell line RT1. We concluded that the
      expression of the p53 protein is related to the viral transfection of cancerous
      cells. The possible role of this phenomenon in the etiology of cancer is
      discussed.

PMID- 9570351
TI  - Serum ceruloplasmin as a diagnostic marker of cancer.
AB  - The pursuit of the ideal tumor marker has generated many tests for use in the
      diagnosis and management of cancer, several of which are now widely available.
      The objective of this study was to evaluate the diagnostic utility as a cancer
      marker of plasmatic levels of ceruloplasmin. Ceruloplasmin is a glucoprotein that
      transports serum copper. A case-control design was used. Serum values were
      evaluated in 144 patients and 103 normal controls by receiver operating
      characteristic (ROC) curve analysis to define the optimal cut-off levels for the
      serum values of ceruloplasmin in the diagnosis of cancer. The ROC analysis showed
      that ceruloplasmin is considerably sensitive in men (80%) at the specificity
      level of 80.3% and in women the sensitivity (Se) was (63.2%) and the specificity
      (Sp) was (63.3%). According to this study, it would seem optimal to use the cut
      off level of 358 mg/l in men and 383 mg/l in women. In conclusion, serum
      ceruloplasmin was significantly elevated in advanced stages of solid malignant
      tumors, however, locally advanced or locoregionally spreading tumors did lead to
      significant increases (P < 0.01). Finally, the results of ROC curve analysis
      suggest that the ceruloplasmin is characteristic of good diagnostic markers.

PMID- 9570352
TI  - Fucose levels in sera and in tumours of colorectal adenocarcinoma patients.
AB  - Fucose levels were determined in normal and tumour-derived tissues from patients
      with colorectal adenocarcinoma. Total, free and bound fucose were significantly
      higher (P < 0.001) in the tumoral tissue. Comparison of serum fucose levels
      between patients with colorectal cancer and control subjects indicated no
      statistically significant differences in total, free and bound fucose expressed
      as nmol/ml serum. However, when total and bound fucose were normalized to total
      protein (nmol/mg protein), an elevation in both parameters was found in
      colorectal cancer patients, although only that for total fucose was statistically
      significant (P < 0.001). A clear association between fucose content and clinical
      stage of patients according to the Dukes' classification can not be established,
      although patients at stage C showed higher levels of fucose both in serum and
      tissue. The current investigation provides direct evidence of a relationship
      between the elevation of fucose and the presence of tumour in colorectal cancer
      patients.

PMID- 9570354
TI  - Apoptosis induced by tea polyphenols in HL-60 cells.
AB  - In order to search for tumor cells apoptosis inducer, the apoptosis effects and
      mechanism of tea polyphenols were studied. Tea polyphenols are active compounds
      purified from tea. The apoptosis effects of tea polyphenols were observed on the
      human promyelocytic leukemic cells (HL-60) by an MTT reduction test, DNA agarose
      gel electrophoresis and a transmission electronic microscopy technique. After HL
      60 cells were treated by tea polyphenols in 250 microg/ml for 5 h, DNA extracted
      from HL-60 cells showed a typical internucleosomal DNA degradation, i.e. DNA
      ladder and apoptotic vehicles were observed. The effects of tea polyphenols were
      shown to be similar to their cytotoxic activity in HL-60 cells. These results
      suggest that the mechanism of antitumor action of tea polyphenols is related to
      its apoptosis-inducing activity.

PMID- 9570353
TI  - Cancer cells isolated from malignant pleural and peritoneal effusions inhibit
      phospholipase A2 activity in human polymorphonuclear leukocytes.
AB  - We studied the influence of cancer cells on the LTB4 production by human
      polymorphonuclear leukocytes (PMN). The cancer cells were isolated from malignant
      pleural effusion specimens taken from two patients or from a peritoneal effusion
      specimen of one patient. While human PMN produced LTB4 following stimulation with
      A23187, the addition of cancer cells inhibited LTB4, 5-HETE and 12-HETE
      production by PMN in a cell number-dependent manner, while the cancer cell lines
      also showed a similar inhibition. The addition of lysate of the breast cancer
      cells also inhibited in a dose-dependent manner the production of LTB4 by PMN
      following stimulation with A23187. The addition of arachidonic acid completely
      reversed the inhibition of PMN-LTB4 production by the addition of the breast
      cancer cell lysates, thus suggesting inhibition at the phospholipase A2 level.
      The addition of this lysate to the partially purified human cytosolic PLA2 also
      inhibited the PLA2 activity. In contrast, the addition of lymphoma cells isolated
      from metastatic lymphnodes did not inhibit the LTB4 production from PMN. Since
      LTB4 is one of the important chemotactic factors for PMN and monocytes, these
      findings suggest that the inhibition of the PLA2 activity by the cancer cells
      thus results in a reduced production of LTB4 from PMN and contributes to a
      predisposition to develop severe infection in patients with advanced cancer.

PMID- 9570355
TI  - Vascular endothelial growth factor (VEGF) expression and survival in human
      epithelial ovarian carcinomas.
AB  - Vascular endothelial growth factor (VEGF) expression and microvessel density were
      studied in cases of advanced epithelial ovarian carcinoma to evaluate their
      usefulness as prognostic variables. Tumor samples from 18 patients with advanced
      stage serous epithelial ovarian cancer were evaluated for VEGF expression by
      reverse-transcriptase polymerase chain reaction (RT-PCR) analysis.
      Immunohistochemical study of corresponding archival tissues with an antibody to
      von Willebrand factor (vWF; FVIII-RA) was used for tumor microvessel count
      determinations. The correlation of VEGF expression and mean microvessel counts
      was determined by an unpaired t-test. Survival analysis for known prognostic
      factors and VEGF expression was performed. Survival distributions were calculated
      by the product limit of Kaplan and Meier and significant differences between
      distributions were analyzed with a log rank test. From the RT-PCR analysis of
      tumor VEGF expression, 12 samples were found to be strongly positive, whereas six
      samples had low/negative VEGF expression. The median survival was 60 months for
      the VEGF-low/negative group and 28 months for the VEGF-positive group (P =
      0.058). Other prognostic variables had minimal impact on survival, i.e. age < 65
      years (P = 0.873), FIGO stage (P = 0.06), grade (P = 0.236) and debulking status
      (P = 0.842). Fourteen of 18 tumor specimens were suitable for microvessel
      counting. The mean microvessel counts of the VEGF-positive group and the VEGF
      negative group were 27/hpf and 35/hpf, respectively (P = 0.16). In this
      preliminary analysis, high VEGF expression in epithelial ovarian carcinomas was
      associated with poor overall survival. Further study will be necessary to
      elucidate the lack of association of VEGF expression and tumor microvessel
      counts.

PMID- 9570356
TI  - Sensitivity of melphalan-resistant tumors to selenite in vivo.
AB  - Previous studies have demonstrated that melphalan-resistant human ovarian tumor
      cells exhibit a higher degree of sensitivity to the cytotoxic effects of selenite
      in vitro than comparable drug-sensitive cells (P.B. Caffrey, G.D. Frenkel,
      Selenite cytotoxicity in drug resistant and non-resistant human ovarian tumor
      cells, Cancer Res. 52 (1992) 4812-4816; P.B. Caffrey, G.D. Frenkel, The
      development of drug resistance by tumor cells in vitro is accompanied by the
      development of sensitivity to selenite, Cancer Lett. 81 (1994) 59-65). We have
      now examined the sensitivity of drug-resistant tumors to selenite in vivo. A2780
      human ovarian tumor cells, or their melphalan-resistant derivative (A2780ME)
      cells were injected subcutaneously into nude mice and the resulting tumors were
      found to be melphalan-sensitive and -resistant, respectively, in vivo. Treatment
      with selenite (2 mg/kg Se s.c.), which had no overt toxic effect on the animals,
      resulted in a significant decrease in the rate of growth of the melphalan
      resistant tumors, but not on the rate of growth of the drug-sensitive tumors.
      Thus, melphalan-resistant ovarian tumors are also more sensitive to selenite
      treatment in vivo.

PMID- 9570357
TI  - Interferon-gamma and retinoic acid down-regulate N-myc in neuroblastoma through
      complementary mechanisms of action.
AB  - The N-myc oncogene plays a key role in the biology of neuroblastoma and the
      differentiation process. N-myc expression is associated with metastatic disease,
      as well as the undifferentiated state of normal neuroblasts migrating from the
      neural crest during embryogenesis. Its down-regulation is a pivotal event in the
      differentiation of neuroblastoma cells by retinoic acid (RA). Our previous work
      has shown that RA works synergistically with other agents, such as interferon
      gamma (IFN-gamma), to down-regulate N-myc expression and induce differentiation.
      The present study demonstrates that IFN-gamma, like RA, decreases N-myc
      transcription. However, functional analysis of N-myc upstream regulatory
      sequences using 5' deletion mutants of a promoter-CAT construct containing germ
      line sequences from nucleotide position -887 to +151 showed that IFN-gamma and RA
      act through different sites on the N-myc promoter. In addition to its
      transcriptional effect, IFN-gamma was also found to shorten the half-life of N
      myc mRNA. Taken together, these findings provide a mechanistic basis for the
      synergistic action of IFN-gamma and RA in inducing neuroblastoma differentiation
      and a rationale for the possible development of combination differentiation
      therapy for clinical use.

PMID- 9570358
TI  - Thyroid carcinoma distinctively expresses intracellular fibronectin in vivo.
AB  - Fibronectin is a multifunctional protein that plays a role in tumor invasion. We
      immunohistochemically examined the in vivo expression of fibronectin in thyroid
      carcinoma in comparison with other carcinomas, such as hepatocellular carcinoma,
      transitional cell carcinoma and gastric adenocarcinoma. Intracellular
      localization of fibronectin was found in almost all cases of thyroid carcinoma.
      In contrast, hepatocellular carcinoma showed a lower expression rate and the
      other carcinomas were all negative. These results indicate that the intracellular
      expression of fibronectin is not a common phenomenon in carcinoma, but rather is
      distinctive for thyroid carcinoma.

PMID- 9570359
TI  - Sonodynamically-induced in vitro cell damage enhanced by adriamycin.
AB  - Sonodynamically-induced cell damage and active oxygen generation enhanced by
      adriamycin (ADM) were compared in the same in vitro insonation set-up.
      Significant enhancement of the rates of both ultrasonically-induced cell damage
      and nitroxide generation was demonstrated with 40-160 microM ADM. Both rates
      correlated very well resulting in a correlation coefficient of more than 0.99.
      The enhancement of both rates was suppressed by 10 mM histidine. These results
      are consistent with the hypothesis that ultrasonically-generated active oxygen
      plays a major role in the sonodynamically-induced cell damage enhanced by ADM.

PMID- 9570360
TI  - p53 protein expression in patients with hepatocellular carcinoma from the high
      incidence area of Guangxi, Southern China.
AB  - Mutation of the p53 gene has been reported in hepatocellular carcinoma (HCC)
      occurring worldwide. The most frequent p53 mutation has been found in HCCs in
      regions with high hepatitis B virus (HBV) infection and intake of aflatoxin B1
      (AFB1). The aim of our study was to examine p53 protein expression in HCCs from a
      high incidence area of Guangxi, Southern China, where HBV infection and dietary
      intake of AFB1 are high. Immunohistochemical staining of p53 protein was carried
      out using a polyclonal rabbit antibody (CM-1). Serial sections were also stained
      for hepatitis B surface antigen and core antigen. p53 Protein expression was
      detected in 13 (43.3%) of the 30 HCCs. Expression of p53 was found in 25.0% (1/4)
      of the < or = 5.0 cm diameter HCCs, in 36.8% (7/19) of the 5.1-10.0 cm diameter
      HCCs and in 71.4% (5/7) of the >10.0 cm diameter HCCs. Expression of p53 was
      observed more in moderately and poorly differentiated than in the well
      differentiated HCCs and more frequently seen in HCCs from younger patients. These
      data indicate that there is a close association between p53 protein expression
      and tumor size, histological grade and age of patients. Twenty-seven out of 30
      cases (90.0%) were positive for HBV. No significant association between p53
      expression and sex. HBV infection, cirrhosis or alpha-fetoprotein has been found.

PMID- 9570362
TI  - LDL-dependent regulation of Bcl-2 and cyclin 'D' gene expression in lymphocytes
      from normal and CML patients.
AB  - Effect of low-density lipoprotein (LDL) on the expression of Bcl-2 as well as
      cyclin 'D' genes was studied in Receptor 'Ck' (+ve) and Receptor 'Ck'(-ve) human
      lymphocytes. LDL had no effect upon the elevated levels of Bcl-2 and cyclin 'D'
      gene products in Receptor 'Ck' (-ve) lymphocytes (from untreated CML patients),
      whereas in Receptor 'Ck' (+ve) lymphocytes (from normal subjects), the exposure
      to LDL regulated the level of cyclin 'D' gene product without initiating the
      expression of bcl-2 gene product. However, blockage of Receptor 'Ck' in normal
      lymphocytes, through its specific antibody (Ab-RCk) in presence or absence of
      LDL, resulted in the induction of both cyclin 'D' (at 4 h interval) and bcl-2 (at
      12 h interval) gene products. Based upon these results, we propose that Receptor
      'Ck' deficiency in cells may inherit defective apoptosis and capacity
      proliferation leading to leukemic transformation.

PMID- 9570361
TI  - Inhibition of initiation and early stage development of aberrant crypt foci and
      enhanced natural killer activity in male rats administered bovine lactoferrin
      concomitantly with azoxymethane.
AB  - The influence of concomitant administration of bovine lactoferrin (bLF) on
      induction of aberrant crypt foci (ACF) by azoxymethane was investigated in male
      F344 rats. Two percent bLF and 3% Bifidobacterium longum (B. longum), as a
      positive control, significantly decreased the numbers of ACF as well as the total
      numbers of aberrant crypts reproducibly in three independent studies (2% bLF, P <
      0.01; 3% B. longum, P < 0.05). Most importantly large size foci composed of four
      or more crypts were always significantly decreased by 2% bLF (P < 0.05).
      Additional investigation of the natural killer activity of spleen cells
      demonstrated enhancement by bLF (P < 0.01) and B. longum (P < 0.01) in line with
      the levels of influence on foci induction, indicating a possible role for
      elevated immune cytotoxicity in the observed inhibition.

PMID- 9570363
TI  - Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC)
      rat.
AB  - We have studied the DNA binding activities of transcription factors in the liver
      of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. Owing to
      a genetic defect, this strain of rats accumulates excessive copper in the liver
      and develops severe hepatitis and hepatocellular carcinoma. We found that the DNA
      binding activity of the serum response factor (SRF) was higher in the liver of
      LEC rats (approximately 2-fold) than in that of Wistar rats. There was a close
      correlation between the intensity of the activity and the concentrations of
      copper in the nuclear protein. The DNA binding activity of Sp1, on the other
      hand, showed similar levels in both LEC and Wistar rats. SRF may play an
      important role in the development of hepatocellular carcinoma in LEC rats by
      mediating the proto-oncogene c-fos induction. We suggest that the copper in
      nuclear protein may be involved in the activation of SRF.

PMID- 9570364
TI  - Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma.
AB  - The imprinted genes, H19 and insulin-like growth factor II (IGF2), have been
      demonstrated to be necessary for embryonal development in humans. Both genes are
      reciprocally imprinted, with expression of the maternal H19 and paternal IGF2
      alleles, and are normally characterized by monoallelic expression. Recently, loss
      of imprinting of these genes producing biallelic expression has been observed in
      childhood tumors including Wilms' tumors (WT), embryonal rhabdomyosarcoma, and
      adulthood tumors such as lung cancer. To test the existence of loss of imprinting
      in hepatocellular carcinoma (HCC), we analyzed the status of imprinting of H19
      and IGF2 genes in three independent tumors, three HCC and one hepatoblastoma cell
      lines using AluI and ApaI polymorphisms of these genes, respectively. In contrast
      to the previous report, all the cases except one tumor and one HCC cell line
      showed biallelic expression of both H19 and IGF2 genes. Unlike WT, loss of
      imprinting (LOI) of IGF2 in HCC was not linked to down-regulation of H19
      expression, but rather associated with coexpression for H19 and IGF2. Thus, Hl9
      and IGF2 expression can be uncoupled in tumors with LOI. The frequent biallelic
      expression of H19 and IGF2 in hepatocellular carcinoma might play a causal role
      in the epigenetic mechanism involved in tumor development and/or process.

PMID- 9570365
TI  - KAI1, a putative marker for metastatic potential in human breast cancer.
AB  - The KAI1 gene maps to chromosome 11p11.2, is a metastasis-suppressor gene for
      human prostate cancer and also is involved in the progression of human pancreatic
      and non-small cell lung cancer. Recently, we showed that introduction of a single
      copy of normal, neomycin-tagged human chromosome 11 into highly metastatic MDA-MB
      435 breast cancer cells suppressed breast cancer metastasis. Concomitantly, KAI1
      levels were higher in chromosome 11/MDA-MB-435 cell clones. The purpose of this
      study was to test whether KAI1 expression is indicative of breast cancer
      metastasis using a panel of immortalized breast epithelial and breast cancer cell
      lines that represent multiple stages of breast cancer progression. Metastatic
      cell clones isolated from the parental mixed, wild-type population of MDA-MB-435
      cells expressed the lowest levels of KAI1 mRNA and chromosome 11 containing MDA
      MB-435 (neo11/MDA-MB-435.A3 and neo11/MDA-MB-435.B1) cells had approximately
      twice as much KAI1 mRNA than the parental clones. MCF-10A, an immortalized normal
      like non-tumorigenic mammary epithelial cell line, had the highest level of KAI1
      mRNA. We compared the metastatic propensity and invasive ability of a continuum
      of breast cancer cells with varying degrees of progression toward malignancy and
      found that these parameters tended to correlate inversely with KAI1 mRNA
      expression. These data suggest that, in addition to its role in human prostate,
      pancreatic and non-small cell lung cancer, KAI1 may also be a useful marker for
      staging human breast disease.

PMID- 9570367
TI  - Can docosahexaenoic acid inhibit metastasis by decreasing deformability of the
      tumor cell plasma membrane?
AB  - Murine leukemia cells were fused with small unilamellar vesicles composed of 1
      stearoyl, 2-docosahexaenoylphosphatidylcholine. The docosahexaenoic acid (DHA)
      modified cells were tested for deformability by forcing them through 5.0-microm
      Nucleopore filters. As the cellular DHA content increased, the cells passed
      through the filters with more difficulty. Furthermore, cells that passed through
      the filters had less DHA than cells that did not. Monitored by steady-state
      fluorescence polarization of membrane interior and surface probes, DHA reduced
      the membrane order in the hydrophobic interior while increasing the order at the
      aqueous interface. We attribute DHA's anti-metastatic properties in part to
      effects on membrane structure that reduce cell deformability.

PMID- 9570366
TI  - Intracellular glutathione content of urothelial cancer in correlation to
      chemotherapy response.
AB  - We evaluated the possible correlation between intracellular glutathione (GSH) and
      drug sensitivity of urothelial cancer. Tissue GSH content of surgical specimens
      from 20 patients with urothelial cancer was assayed with high performance liquid
      chromatography (HPLC). GSH levels of cancer tissue (7.887 +/- 6.176 microM/mg
      protein) were significantly higher than GSH levels of normal mucosa (1.345 +/-
      1.252 microM/mg). All patients having measurable lesions were then treated with
      methotrexate, epirubicin and cisplatin (MEC). These patients were classified into
      three groups according to clinical response criteria. GSH content in cancer
      tissue from four patients with complete response was 0.804 +/- 1.183 microM/mg
      protein. However, the cancer cells from patients with partial response and non
      response contained a significantly higher level of GSH (6.295 +/- 2.459 (n = 8)
      and 12.955 +/- 6.141 microM/mg protein (n = 8), respectively). Intracellular
      glutathione content may play an important role in intrinsic resistance of
      urothelial cancer to MEC chemotherapy. It might be potentially used to predict
      drug sensitivity in urothelial cancer patients before starting chemotherapy.

PMID- 9570368
TI  - Role of ceramide in suramin-induced cancer cell death.
AB  - Suramin is an experimental antineoplastic agent which is currently being tested
      in clinical trials for its utility in treating breast and prostate cancer. Recent
      in vitro studies from our laboratory report a disruption in glycolipid metabolism
      and cell death in suramin-treated neurons. Evidence presented in this study
      proposes to consolidate the neurotoxic and cytotoxic effects of suramin. Electron
      microscopic studies, bis-benzimide staining and DNA gel electrophoresis of
      suramin and C2-ceramide treatment revealed apoptotic cells in human breast,
      prostate and rat neuron like cell lines. Apoptotic cell death was preceded by an
      elevation in intracellular ceramide.

PMID- 9570369
TI  - Wild-type p53 gene increases MDR1 gene expression but decreases drug resistance
      in an MDR cell line KBV200.
AB  - Inactivation of p53 gene and overexpression of MDR1 gene are both associated with
      drug resistance. Previous studies have suggested that p53 gene can modulate the
      expression activity of MDR1 gene promoter in a promoter-CAT system. In the
      present study, wild-type p53 gene cDNA was introduced into a multidrug-resistant
      cell line, KBv200, in which endogenous p53 gene is aberrant. In wt-p53
      transfected cells, the expression of MDRI gene was significantly increased,
      accumulation of adriamycin (ADM) was decreased, and the sensitivity to
      vincristine (VCR), ADM and 5-fluorouracil (5-FU) was increased compared with the
      parent KBv200 cells. After treatment with ADM and VCR, the p53-transfectants were
      more susceptible to apoptosis. The results suggest that the increase in drug
      sensitivity of the cells may be, at least in part, due to p53-dependent apoptosis
      induced by anticancer agents.

PMID- 9570370
TI  - Induction of novel Grp75 isoforms by 2-deoxyglucose in human and murine
      fibroblasts.
AB  - Grp75 is a stress-inducible mitochondrial chaperone which has a high homology to
      senescence-related protein, p66mot mortalin. In human cells the mortalin gene
      assigns to the locus of a putative tumor suppressor gene for myeloid
      malignancies. In order to study expression and localization of Grp75 and p66mot
      in human and murine fibroblast lines, polyclonal antibodies were raised to
      conserved portions of each sequence. HT1080 and C3H10T1/2 cells were treated with
      various Grp-inducing agents. A single 75 kDa band was detected by Western blot of
      cytoplasmic proteins which was not greatly altered after thermal stress or
      treatment with L-azetidine-2-carboxylic acid or nonactin. However, glucose
      deprivation by 2-deoxyglucose treatment induced five novel isoforms at 74-75 kDa
      mass. Mortalin at 66 kDa could not be detected under these treatment conditions.

PMID- 9570371
TI  - The role of the cytoskeleton in migration and proliferation of a cultured human
      gastric cancer cell line using a new metastasis model.
AB  - Using an in vitro model for investigating the mechanism of migration and
      proliferation of a cultured human gastric cancer cell line which we established
      recently, we studied the suppressive effect of inhibitors of the cytoskeleton
      proteins, actin and myosin, on the migration and proliferation of cancer cells.
      These inhibitors suppressed the capacity of cancer cells to migrate and
      proliferate dose-dependently. Thus the integrity of the cytoskeletal system may
      play an important role in the mechanism of metastasis of gastric cancer cells.

PMID- 9570372
TI  - Postnatal efficacy of antioxidants in the detoxification pathway of suckling
      neonates and lactating mice.
AB  - This study evaluates the comparative efficacy of antioxidant vitamins (ascorbic
      acid and alpha-tocopherol) and non-vitamin antioxidants (glutathione, cysteine
      and L-2-oxothiazolidine-4-carboxylate (OTZ)) in modulating the detoxification
      pathway of lactating dams and suckling murine pups. In dams, 100 mg/kg b.w./day
      treatment of each of the vitamin and non-vitamin antioxidants induced a
      significant increase in the hepatic level of acid soluble sulfhydryl (-SH)
      compared to the modulating efficiency of OTZ, glutathione and alpha-tocopherol in
      the kidney tissue. In the liver and kidney tissues of suckling pups OTZ and alpha
      tocopherol were effective in modulating the -SH level. A statistically
      significant increase in the hepatic glutathione-S-transferase (GST) level was
      observed by OTZ, glutathione and alpha-tocopherol, while only OTZ was effective
      in the kidney tissue of dams and pups. In the murine system, the modulation of
      cellular GST/GSH status, specifically by OTZ, alpha-tocopherol and interacting
      antioxidant pool, may potentially ameliorate the pathophysiology of oxidative
      stress.

PMID- 9570373
TI  - Phloretin-induced apoptosis in B16 melanoma 4A5 cells by inhibition of glucose
      transmembrane transport.
AB  - Phloretin, a naturally occurring dihydrochalcone, is known to inhibit tumor cell
      growth in vitro and in vivo. To clarify the anti-tumor effects of phloretin, its
      apoptosis-inducing effects in B16 melanoma 4A5 cells were examined. Phloretin
      induced the internucleosomal DNA fragmentation typical of apoptosis in B16
      melanoma cells. The addition of extracellular glucose remarkably inhibited the
      phloretin-induced apoptosis in the cells. When apoptosis was strongly induced in
      the B16 cells by phloretin, protein kinase C activity was inhibited in the cells.
      Our results suggest that phloretin induced apoptosis in B16 melanoma 4A5 cells
      mainly through the inhibition of glucose transmembrane transport. Inhibition of
      protein kinase C activity by phloretin probably promotes the ratio of apoptotic
      cells in the cells.

PMID- 9570374
TI  - New quinolones, ofloxacin and levofloxacin, inhibit telomerase activity in
      transitional cell carcinoma cell lines.
AB  - It has been demonstrated that some quinolone antibiotics inhibit cell
      proliferation in vitro. This study showed that ofloxacin and levofloxacin, two
      well-known new quinolones, had an inhibitory effect on the proliferation of
      transitional cell carcinoma cell lines at high concentrations (>200 microg/ml).
      At relatively low concentrations (10-100 microg/ml), however, there was no
      apparent antiproliferative effect. Despite this, decreased absorbance in the MTT
      assay was observed at low concentrations and telomerase activity was
      significantly decreased. These results suggest that the antiproliferative effect
      of both ofloxacin and levofloxacin may be related to impairment of telomerase
      activity by some unknown mechanism.

PMID- 9570375
TI  - Comparison of the therapeutic effects of two vanadium complexes administered at
      low dose on benzo[a]pyrene-induced malignant tumors in rats.
AB  - The antitumor effects of low dose administration of the vanadium(III) complexes
      with L-cysteine (complex 1) and N-(2-mercaptopropionyl)-glycine (complex 2) were
      compared on benzo[a]pyrene (BaP)-induced tumors in Wistar rats. Male Wistar rats,
      injected with 10.0 mg of BaP, were divided into one control (C-G) and two
      treatment (TR-G) groups of 17 animals each. Animals of the first treatment group
      were administered complex 2 (TR-2 group) and those of the second group were
      administered complex 1 (TR-1 group) at doses of 100 microg of vanadium per os
      daily, starting from the day a palpable tumor was developed till their death. BaP
      injection induced a 100% tumor (leiomyosarcomas) development in the animals of
      all groups. Administration of complex 1 to the animals resulted in a significant
      prolongation of the mean survival time, a complete remission of 17.6% of the
      tumors developed, a significant reduction of the carcinogenic potency (CP) of BaP
      and of the tumor growth rate (TGR) in TR-1 group animals, compared to the control
      and the TR-2 group. In marked contrast, complex 2 failed at the doses
      administered to exert any significant modulation of the above mentioned
      parameters. Results indicate that at low (100 micro/day) concentrations of
      vanadium, complex 1 exerts a significant anticarcinogenic effect on
      experimentally-induced leiomyosarcomas in rats, whereas complex 2 has no effect
      when administered at the same low concentrations of vanadium.

PMID- 9570376
TI  - Association of vascular endothelial growth factor expression with tumor
      angiogenesis, survival and thymidine phosphorylase/platelet-derived endothelial
      cell growth factor expression in human colorectal cancer.
AB  - To examine the association of vascular endothelial growth factor (VEGF)
      expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet
      derived endothelial cell growth factor (dThdPase/PD-ECGF) expression in human
      colorectal cancer, immunohistochemical studies were performed on 136 cases of
      resected colorectal cancer specimens using antibodies for VEGF, KDR, CD34 and
      dThdPase/PD-ECGF. Fifty-nine cases (43%) were evaluated as positive for VEGF
      staining and 71 cases (52%) were evaluated as positive for dThdPase/PD-ECGF
      staining. The expression of VEGF correlated significantly with vessel counts and
      the expression of dThdPase/PD-ECGF (P = 0.01 and 0.01, respectively). Cox
      proportional hazards model analysis showed that vessel counts and VEGF expression
      were significant and independent prognostic factors, but that KDR expression was
      not.

PMID- 9570377
TI  - Lack of mda-6/WAF1/CIP1-mediated inhibition of cyclin-dependent kinases in
      interferon-alpha resistant murine B16 melanoma cells.
AB  - Previously we demonstrated that IFN-alpha augments mda-6/WAF1 and inhibits cyclin
      dependent kinases in a p53-independent fashion in B 16 murine melanoma cells. On
      the other hand, IFN-gamma activates p53 expression without affecting the mda
      6/WAF1 system. Combination of the two IFNs is additive. B16 cells acquire IFN
      alpha resistant but IFN-gamma sensitive phenotype after long term IFN-alpha
      treatment (B16alpha cells). Here we demonstrate the absence of mda-6/WAF1
      associated repression of cyclin-dependent kinases, but the existence of p53
      dependent c-myc inhibition in IFN-gamma-treated B16alpha cells. Clearly,
      selective desensitization of IFN-alpha related growth regulation does not
      influence the IFN-gamma associated pathway. Our results further support the
      coexistence of distinct growth regulatory mechanisms in B16 cells that can be
      activated by different IFN-types independently of each other.

PMID- 9570378
TI  - Advanced non-small cell lung cancer chemotherapy: a randomized trial of two
      active regimens (MVP and PE).
AB  - The treatment of advanced or metastatic NSCLC remains a controversial issue and
      cisplatin-based combination chemotherapy is by far the most common treatment. Two
      of these cisplatin-based standard combinations, MVP and PE, were compared in this
      study in order to evaluate their response rates and survival times. Eighty-five
      previously untreated NSCLC patients were randomly selected to receive either MVP
      or PE and 72 of these patients were eligible for evaluation for response rate and
      survival. Response rates for MVP were: CR 11%, PR 35%, SD 19% and PD 35% and for
      PE: CR 0%, PR 26%, SD 22% and PD 52%. The median survival time was 9.7 months for
      MVP and 6.9 months for PE. Both schedules were well tolerated. The administration
      of MVP in advanced NSCLC resulted in superior response rates and survival times
      over those produced by PE.

PMID- 9570379
TI  - A screening method of SH2 domain ligands and blockers using a solid phase
      binding.
AB  - We have developed a high throughput screening method for SH2 domain binding
      ligands and blockers. This method measures directly the binding of a 3H-labeled
      phosphopeptide derived from the sequence around tyrosine317 in the human Shc
      (SpYVNVK) to the SH2 domain of Grb2, which is precoated as glutathione S
      transferase fusion proteins on solid phase. The optimum concentration for the
      fusion protein coating was 300 ng/100 microl/well for SH2 domain binding.
      Although an 8-h incubation at 4 degrees C for the coating of fusion protein was
      required to reach a maximum binding, even a 2-h coating produced 84% of the
      maximum binding. Saturation of ligand peptide binding in our assay system was
      observed at 10 pmol/well for the SH2 domain. However, 2 pmol/well showed
      consistent and reproducible results for the binding when the incubations were
      performed for 8 h at 4 degrees C. Competitive binding inhibition studies with
      various unlabeled phosphopeptides imply that the binding assay is highly specific
      to peptide sequences and able to screen possible ligands or blockers of signal
      transduction pathway mediated by Grb2 SH2 binding. In conclusion, our new method
      for SH2 domain binding is easy, rapid, and most of all inexpensive. These
      advantages over existing assay methods make this method especially suitable for a
      high throughput application, such as the screening for anticancer drug
      candidates.

PMID- 9570380
TI  - Loss of imprinting and overexpression of IGF2 gene in gastric adenocarcinoma.
AB  - Both insulin-like growth factor II (IGF2) and H19 gene are located on chromosome
      11p15.5 in close vicinity to each other, and are imprinted on different parental
      alleles. Although the exact mechanism remains unclear, loss of imprinting (LOI)
      leading to the biallelic expression of IGF2 and H19 genes has recently been
      reported in a variety of tumors. To study the role of IGF2 and H19 genes in
      gastric carcinogenesis, the LOI and loss of heterozygosity (LOH) status of these
      two genes were determined in 70 patients with gastric cancer. Among them, 30
      patients were heterozygous for IGF2, 28 patients were heterozygous for H19, and
      42 patients were heterozygous for either IGF2 or H19 gene. Among the 30 patients
      who were heterozygous for IGF2, one exhibited LOH (1/30, 3.3%) and 10 exhibited
      LOI (10/29, 34.5%). None of the 28 patients heterozygous for H19 gene had either
      LOH or LOI. LOI of IGF2 was more frequently found in the diffuse type (8/15,
      53.3%) than the intestinal type (2/14, 14.3%, P < 0.05) gastric cancer. Five out
      of the six tumors with LOI of IGF2 exhibited overexpression of mRNA, but no
      obvious alterations of expression of H19 were noted by Northern hybridization.
      These data suggest that LOI leading to overexpression of IGF2 plays an important
      role in carcinogenesis of diffuse type gastric cancer.

PMID- 9570382
TI  - Estrogen receptor-negative/progesterone receptor-positive Evsa-T mammary tumor
      cells: a model for assessing the biological property of this peculiar phenotype
      of breast cancers.
AB  - In 1986 we reported the appearance of a progestin binding protein in the human
      breast cancer cell line Evsa-T, originally described as lacking both estrogen and
      progesterone receptors (ER and PR). In this report we show that PR of this cell
      line displays a binding affinity for [3H]ORG 2058 and a sucrose gradient
      sedimentation profile similar to those ascribed to PR from MCF-7 or T47D breast
      cancer cell lines. PR from Evsa-T cells is down-regulated by the progestin R-5020
      as well as by the two antiprogestins, ZK 112.993 and ZK 98.299, but does not
      confer growth sensitivity to these compounds. ER remains undetectable by ligand
      binding assay, enzyme immunoassay and northern blotting. Our Evsa-T clone could
      be a valuable model for assessing the mechanisms leading the ER-/PR+ phenotype
      occurring occasionally in breast cancers and frequently in meningiomas.

PMID- 9570381
TI  - Chemoprevention by lycopene of mouse lung neoplasia after combined initiation
      treatment with DEN, MNU and DMH.
AB  - An investigation was conducted to assess the chemopreventive potential of
      lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and
      their products, administered during the post-initiation stage in a multiorgan
      carcinogenesis model. One hundred eighteen B6C3F1 mice of both sexes were
      subjected to combined treatment with diethylnitrosamine (DEN), N-methyl-N
      nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH) from day 11 after birth to week
      9 (DMD treatment) (groups 1 and 2) or their vehicles (group 3). Then group 1
      received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32.
      Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or
      50 ppm). All surviving animals were sacrificed at week 32 and the major organs,
      including the liver, lung, kidney and colon, were histologically examined. The
      incidences and multiplicities of lung adenomas plus carcinomas combined in male
      mice in group 1 receiving 50 ppm LP were significantly decreased as compared to
      the DMD alone or DMD and 25 ppm LP groups (75.0 versus 18.8%, P < 0.02; 0.94 +/-
      0.17 versus 0.25 +/- 0.14, P < 0.001). No such effect was observed for females.
      Although hepatocellular carcinomas were lacking in the DMD and LP groups while
      two cases were found in the DMD alone group, this difference was not
      statistically significant. The values for aberrant crypt foci (ACF) and tumors in
      the colon and kidney did not show any significant variation among the carcinogen
      treated subgroups. The results suggest that LP exerts a chemopreventive effect
      limited to male lung carcinogenesis when given in the post-initiation stage to
      B6C3F1 mice.

PMID- 9570383
TI  - Inhibition of human malignant glioma cell motility and invasion in vitro by
      hypericin, a potent protein kinase C inhibitor.
AB  - The effect of hypericin, an antiviral drug and a potent protein kinase C (PKC)
      inhibitor, on glioma cell invasion was investigated in vitro. Treatment of the
      established human glioblastoma cell line, T98G, with 1 microM hypericin for 24 h
      resulted in a significant inhibition of the cell invasion through an artificial
      basement membrane, but not cell attachment or proliferation. Furthermore,
      tamoxifen and staurosporine, both PKC inhibitors, also inhibited T98G cell
      invasion, suggesting that PKC may be the cellular target for hypericin-inhibited
      glioma cell migration. Similarly, hypericin decreased cell motility significantly
      in established lines, T98G and U87-MG, and also in a low-passage human malignant
      glioma cell line. Thus, hypericin may prove useful for studying mechanisms of
      glioma invasion, and may represent a new agent in malignant glioma therapy.

PMID- 9570384
TI  - Deletion of the M6P/IGF2r gene in primary hepatocellular carcinoma.
AB  - To evaluate the different alteration patterns of the mannose 6-phosphate/insulin
      like growth factor 2 receptor (M6P/IGF2r) gene in hepatocellular carcinoma (HCC),
      41 HCCs were screened for homozygous deletion and loss of heterozygosity (LOH) at
      the M6P/IGF2r gene with a dinucleotide repeat polymorphic marker. Of these, three
      (8.8%) were heterozygous and LOH was observed in two (66.7%) of these informative
      cases. Five (14.7%) out of 34 informative cases showed homozygous deletions for
      the dinucleotide repeat polymorphic marker. The frequent allelic loss and
      homozygous deletion of the M6P/ IGF2r gene suggest that the M6P/IGF2r gene
      functions as a tumor suppressor gene in the development of HCC.

PMID- 9570385
TI  - Binding of monomeric and oligomeric porphyrins to human glioblastoma (U-87MG)
      cells and their photosensitivity.
AB  - The binding of monomeric (Hp) and oligomeric (PHE) forms of porphyrin to
      glioblastoma (U-87MG) cells and the photosensitization of these cells have been
      studied. Upon binding to U-87MG cells, Hp and PHE exhibited fluorescence bands at
      615 and 636 nm, respectively. The fluorescence and absorption spectra of Hp, HpD
      and PHE, measured in different solvents, suggest that the 615 nm band may arise
      due to the binding of monomeric as well as aggregated forms of porphyrin to the
      hydrophilic sites in the cells whereas the 636 nm band may be due to the binding
      of an aggregated form of porphyrin to the hydrophobic sites. The photosensitivity
      of cells and photo-induced lipid peroxidation were measured as a function of
      light dose. Cells were found most photosensitive to PHE followed by HpD and Hp.
      The photosensitivity of cells correlates well with the fluorescence intensity of
      cell bound dye at 636 nm. These results suggest that the binding of the
      oligomeric component of HpD to hydrophobic sites in the cells is responsible for
      the enhancement in the photosensitivity.

PMID- 9570387
TI  - Effects of vitamin D3 on proliferation of cancer cells in vitro.
AB  - The principal cause of death from most forms of cancer is metastatic disease.
      Cancer cells appear to grow quickly out of the control of the normal host
      regulatory mechanisms. Many factors contribute to this unrestrained
      proliferation, including increased metalloproteinase activity causing degradation
      of the extracellular matrix surrounding cancer cells, angiogenesis permitting
      easy access of the cells to the bloodstream and decrease or loss of programmed
      cell death, or apoptosis, an important mechanism for removal of abnormal or
      senescent cells. Treatment modalities targeted towards arresting cancer cell
      proliferation and spread are needed to improve the survival of patients with
      cancer. Vitamin D3, 1,25-dihydroxychole-calciferol D3, has been shown to induce
      apoptosis in the human breast cancer cell line, MCF-7. We have studied the
      effects of three concentrations of vitamin D3 on the human breast cancer cell
      line, MDA-MB-435, the human prostate cancer cell line, LNCaP, and a human
      osteosarcoma cell line, U20S. We report here that vitamin D3 strikingly inhibits
      cell proliferation and induces apoptosis in all three cell lines.

PMID- 9570386
TI  - Inhibition of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor growth by
      aryl hydrocarbon receptor agonists.
AB  - The antitumorigenic activities of 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF),
      8-methyl-1,3,6-trichlorodibenzofuran (8-MCDF) and 6-cyclohexyl-1,3,8
      trichlorodibenzofuran (6-CHDF) were investigated in the 7,12
      dimethylbenz[a]anthracene (DMBA) rat mammary tumor model. At doses of 5, 10 or 25
      mg/kg/week, both 6-MCDF and 8-MCDF significantly inhibited mammary tumor growth
      and at the 5 mg/kg/week dose >50% growth inhibition was observed. In contrast, 6
      CHDF was inactive at the 5 mg/kg/week dose and the structure-antitumorigenicity
      relationships (6-MCDF/8-MCDF > 6-CHDF) correlated with structure
      antiestrogenicity (rat uterus) studies and the relative binding affinities of
      these compounds for the aryl hydrocarbon receptor (AhR). The antitumorigenic
      activity of 6-MCDF or 8-MCDF in the mammary was not accompanied by any
      significant changes in liver/body weight ratios, liver morphology or induction of
      hepatic CYP1A1-dependent activity which is one of the most sensitive indicators
      of exposure to AhR agonists. RT-PCR and Western blot analysis of mammary tumor
      mRNA and protein extracts, respectively, confirmed the presence of AhR suggesting
      that AhR-mediated signaling pathways are functional in rat mammary tumors. These
      results define a relatively non-toxic group of AhR agonists which exhibit potent
      antitumorigenic activity in the DMBA-induced rat mammary tumor model (<1
      mg/kg/day), and therefore represent a new class of indirect-acting antiestrogens
      which have potential for clinical treatment of mammary cancer.

PMID- 9570388
TI  - Detection of medulloblastoma and astrocytoma-associated ganglioside GD3 in
      cerebrospinal fluid.
AB  - Shedding of gangliosides by tumor cells may enhance tumor development. We
      recently showed that cells of the human brain tumor, medulloblastoma, shed
      gangliosides in vitro and have therefore examined ganglioside shedding by
      pediatric brain tumors into the cerebrospinal fluid (CSF). GD3, a major
      ganglioside in medulloblastoma and astrocytoma, was the target for detection in
      the CSF by immunostaining using the monoclonal antibody R24 and enhanced
      chemiluminescence detection. Mean CSF GD3 levels in patients with
      medulloblastomas (n = 9) and astrocytomas (n = 10) were significantly higher than
      those of controls (mean +/- SD 44.7 +/- 8.4 versus 18.2 +/- 1.9 pmol/ml, n = 20,
      P < 0.0002). Mass spectrometric analysis showed that tumor-derived ganglioside
      GD3 contained heterogeneous ceramide structures and, interestingly, the ceramide
      subspecies with shorter fatty acyl chains were selectively shed. The elevated CSF
      GD3 concentrations in patients with medulloblastoma and astrocytoma support the
      concept that ganglioside shedding, which may have significant biological
      consequences, is characteristic of human brain tumors.

PMID- 9570389
TI  - Failure of the cultivated mushroom (Agaricus bisporus) to induce tumors in the
      A/J mouse lung tumor model.
AB  - We studied whether the cultivated mushroom (Agaricus bisporus) or 4
      (carboxy)phenylhydrazine (CP) induce lung adenomas in the A/J mouse lung tumor
      model. For 26 weeks female mice were fed a semisynthetic diet where 11 or 22% of
      the diet was replaced by freeze-dried mushrooms. The intake of the mushroom diets
      was equivalent to an intake of agaritine, the major phenylhydrazine derivative
      occurring in the mushroom, of 92 or 166 mg/kg body weight per day. The intake of
      CP was 106 mg/kg body weight per day. Neither the freeze-dried mushroom nor CP
      induced statistically significant increased numbers of lung adenomas in female
      A/J mice in the administered dosages.

PMID- 9570390
TI  - Synergistic effect of MNU and DMBA in mammary carcinogenesis and H-ras activation
      in female Sprague-Dawley rats.
AB  - The combined application of N-methyl-N-nitrosourea (MNU) and 7,12
      dimethylbenz[alpha]anthracene (DMBA) was compared with the administration of each
      carcinogen alone as to the effectiveness of the induction of mammary carcinomas
      and the influence of H-ras oncogene activation in female Sprague-Dawley rats. At
      50 days of age, group 1 received 30 mg/kg MNU intraperitoneally (i.p.), group 2
      received 30 mg/kg DMBA i.p., group 3 received 60 mg/kg MNU i.p., group 4 received
      60 mg/ kg DMBA i.p., group 5 received 30 mg/kg MNU followed by 30 mg/kg DMBA
      i.p., group 6 received 30 mg/kg MNU i.p. and then 30 mg/kg DMBA intravenously
      (i.v.) and group 7 remained untreated. Animals were killed when the largest
      mammary tumor reached 1-2 cm in diameter or were necropsied when they were 30
      weeks of age. MNU i.p. produced no deaths (groups 1 and 3), however, the i.p.
      administration of DMBA induced death due to peritonitis (groups 2, 4 and 5),
      whereas the i.v. administration of DMBA suppressed the death (group 6). All of
      the tumors produced by MNU were adenocarcinomas of mammary origin. In contrast,
      DMBA produced tumors of other than mammary origin. The combined treatment with
      DMBA and MNU increased the mammary carcinogenic effect; it significantly
      increased the mean number of mammary cancers per rat. With either carcinogen
      alone and in combination, the mammary carcinomas produced identical
      adenocarcinoma histology. Of the mammary carcinomas induced by the combined
      application of MNU and DMBA (group 6), all 11 tumors from five rats showed the
      GGA to GAA transitional mutation in H-ras codon 12 (38%) and all 18 tumors from
      the other 10 rats remained as wild-type. An H-ras point mutation at codon 61 was
      not detected.

PMID- 9570391
TI  - Failure of dietary alpha-difluoromethylornithine to inhibit gastric
      carcinogenesis in rats after 8 weeks of treatment with N-methyl-N'-nitro-N
      nitrosoguanidine and sodium chloride.
AB  - The modifying effects of alpha-difluoromethylomithine (DFMO) on glandular stomach
      carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      and sodium chloride were investigated in male outbred Wistar rats. Animals were
      simultaneously given MNNG solution (100 ppm) as their drinking water and diet
      supplemented with 10% sodium chloride for 8 weeks, and administered DFMO (dietary
      levels of 2000 ppm or 500 ppm) and tap water for the following 70 weeks. The DFMO
      treatment did not show any tendency to inhibit the development of gastric
      adenocarcinomas. The incidences and multiplicities of atypical hyperplasias in
      the glandular stomachs were also comparable in all groups of rats given
      MNNG/sodium chloride. Neither gastric carcinomas nor atypical hyperplasias were
      observed without the carcinogen treatment. Thus, DFMO did not exert any
      inhibitory effects when given during the post-initiation phase of two-stage
      glandular stomach carcinogenesis in rats initiated with MNNG and sodium chloride
      for 8 weeks.

PMID- 9570392
TI  - Interleukin-8 participates in angiogenesis in non-small cell, but not small cell
      carcinoma of the lung.
AB  - We examined interleukin-8 (IL-8) production in 17 lung cancer cell lines, IL-8
      expression in tumor specimens and IL-8's contribution to tumor-induced
      angiogenesis in vivo. Eight of 13 non-small cell lung cancer cell lines
      constitutively produced high levels of IL-8. Four small cell lung cancer cell
      lines produced little or no IL-8. Immunohistochemical analysis of transbronchial
      biopsy specimens revealed IL-8 staining within adenocarcinomas (22/32), squamous
      cell carcinomas (12/21) and large cell carcinomas (2/3), but not within most
      small cell carcinomas (1/22). Anti-IL-8 antisera blocked tumor angiogenesis by
      two IL-8 producing cell lines in a mouse model.

PMID- 9570393
TI  - Positive correlation between inhibitors of matrix metalloproteinase 1 and matrix
      metalloproteinases in malignant ovarian tumor tissues.
AB  - To investigate the relation between matrix metalloproteinases (MMP) and tissue
      inhibitors of metalloproteinases (TIMP) in malignant ovarian tumor, MMP and TIMP
      activities in conditioned media of 16 malignant ovarian tumor tissues and six
      normal ovaries were detected by zymography and reverse zymography, respectively
      and were quantitated with a densitometer. TIMP-1 and TIMP-2 were detected in all
      normal and malignant ovarian tumor tissues by reverse zymography. In normal
      ovaries, the intensity of TIMP-2 bands was stronger than TIMP-1, but in malignant
      tumor tissues those of TIMP-1 were stronger. The ratios of TIMP-1 to TIMP-2 and
      MMP-9 to MMP-2 were significantly higher in malignant tumor tissues than in
      normal ovaries (P < 0.001). TIMP activity consisting of TIMP-1 and TIMP-2
      correlated significantly to MMP activity of MMP-2 and MMP-9 (r = 0.67, P <
      0.005). There was a significant correlation between TIMP-1 activity and MMP
      activity (r = 0.72, P < 0.001), but no correlation was observed between TIMP-2
      activity and MMP activity. The high level of TIMP-1 appeared to be related to
      malignant phenotype in ovaries as well as the high level of MMP-9.

PMID- 9570394
TI  - Potent suppressing activity of the non-polyphenolic fraction of green tea
      (Camellia sinensis) against genotoxin-induced umu C gene expression in Salmonella
      typhimurium (TA 1535/pSK 1002)--association with pheophytins a and b.
AB  - Antigenotoxic and antimutagenic activities of green tea extract and tea-derived
      polyphenols have been studied using in vitro and in vivo experiments. However,
      antigenotoxic substances in the non-polyphenolic fraction of green tea have been
      poorly elucidated. In the present study, the effect of the non-polyphenolic
      fraction of green tea on genotoxin-induced umu C gene expression was analyzed
      using a tester bacteria, and potent antigenotoxic substances in the non
      polyphenolic fraction were identified. The non-polyphenolic fraction of green tea
      showed strong suppressive activities against umu C gene expression in Salmonella
      typhimurium (TA 1535/pSK 1002) induced by 3-amino-1,4-dimethyl-5H-pyrido[4,3
      b]indol (Trp-P-1) or mitomycin C (MMC) in the presence or absence of S9
      metabolizing enzyme mixture. The non-polyphenolic fraction of green tea exhibited
      major two-color bands in a silica gel TLC and they were identified as chlorophyll
      related compounds, pheophytins a and b, judged by their specific colors, Rf
      values in silica gel TLC and absorption spectra. These pigments showed
      significant suppressive activities against umu C gene expression in tester
      bacteria induced by Trp-P- and MMC in a dose-dependent manner. These results
      suggest that the non-polyphenolic fraction of green tea contains pheophytins a
      and b as potent antigenotoxic substances.

PMID- 9570395
TI  - Simple sequence repeats in the Helicobacter pylori genome.
AB  - We describe an integrated system for the analysis of DNA sequence motifs within
      complete bacterial genome sequences. This system is based around ACeDB, a genome
      database with an integrated graphical user interface; we identify and display
      motifs in the context of genetic, sequence and bibliographic data. Tomb et aL
      (1997) previously reported the identification of contingency genes in
      Helicobacter pylori through their association with homopolymeric tracts and
      dinucleotide repeats. With this as a starting point, we validated the system by a
      search for this type of repeat and used the contextual information to assess the
      likelihood that they mediate phase variation in the associated open reading
      frames (ORFs). We found all of the repeats previously described, and identified
      27 putative phase-variable genes (including 17 previously described). These could
      be divided into three groups: lipopolysaccharide (LPS) biosynthesis, cell-surface
      associated proteins and DNA restriction/modification systems. Five of the
      putative genes did not have obvious homologues in any of the public domain
      sequence databases. The reading frame of some ORFs was disrupted by the presence
      of the repeats, including the alpha(1-2) fucosyltransferase gene, necessary for
      the synthesis of the Lewis Y epitope. An additional benefit of this approach is
      that the results of each search can be analysed further and compared with those
      from other genomes. This revealed that H. pylori has an unusually high frequency
      of homopurine:homopyrimidine repeats suggesting mechanistic biases that favour
      their presence and instability.

PMID- 9570396
TI  - Non-genetic population heterogeneity studied by in situ polymerase chain
      reaction.
AB  - Expression of a lac operon in Salmonella typhimurium single cells was monitored
      using lac mRNA targeting in situ reverse transcription-polymerase chain reaction
      (RT-PCR). It is demonstrated that suboptimal induction of the lac operon in a
      culture of S. typhimuriuml/F'lac+ cells generates a subpopulation in which
      transcription of the lac operon occurs and another subpopulation in which
      transcription of the lac operon is repressed, whereas suboptimal induction of the
      lac operon in a culture of S. typhimuriuml/F'lacY cells generates a population
      with uniform levels of lac mRNA. The outcome of the single-cell lac mRNA
      detection assay was compared with the outcome of a single-cell beta-galactosidase
      assay. In cultures grown under different suboptimal lac induction conditions, the
      fraction of cells in which transcription of the lac operon occurred was
      concurrent with the fraction of cells showing beta-galactosidase activity.
      Besides supporting the hypothesis that the lactose permease has a role in
      generating non-genetic heterogeneity in suboptimally induced cultures of Lac+
      cells, these results demonstrate the usefulness of in situ RT-PCR for the study
      of non-genetic population heterogeneities.

PMID- 9570397
TI  - Reconstruction of the proteolytic pathway for use of beta-casein by Lactococcus
      lactis.
AB  - Amino acid auxotrophous bacteria such as Lactococcus lactis use proteins as a
      source of amino acids. For this process, they possess a complex proteolytic
      system to degrade the protein(s) and to transport the degradation products into
      the cell. We have been able to dissect the various steps of the pathway by
      deleting one or more genes encoding key enzymes/components of the system and
      using mass spectrometry to analyse the complex peptide mixtures. This approach
      revealed in detail how L. lactis liberates the required amino acids from beta
      casein, the major component of the lactococcal diet. Mutants containing the
      extracellular proteinase PrtP, but lacking the oligopeptide transport system Opp
      and the autolysin AcmA, were used to determine the proteinase specificity in
      vivo. To identify the substrates of Opp present in the casein hydrolysate, the
      PrtP-generated peptide pool was offered to mutants lacking the proteinase, but
      containing Opp, and the disappearance of peptides from the medium as well as the
      intracellular accumulation of amino acids and peptides was monitored in peptidase
      proficient and fivefold peptidase-deficient genetic backgrounds. The results are
      unambiguous and firmly establish that (i) the carboxyl-terminal end of beta
      casein is degraded preferentially despite the broad specificity of the
      proteinase; (ii) peptides smaller than five residues are not formed in vivo;
      (iii) use of oligopeptides of 5-10 residues becomes only possible after uptake
      via Opp; (iv) only a few (10-14) of the peptides generated by PrtP are actually
      used, even though the system facilitates the transport of oligopeptides up to at
      least 10 residues. The technology described here allows us to monitor the fate of
      individual peptides in complex mixtures and is applicable to other proteolytic
      systems.

PMID- 9570398
TI  - Mutational analysis of the NH2-terminal arms of the trp repressor indicates a
      multifunctional domain.
AB  - The NH2-terminal arms of the Escherichia coli trp repressor have been implicated
      in three functions: formation of repressor-operator complexes via association
      with non-operator DNA; stabilization of repressor oligomers bound to DNA; and
      oligomerization of the aporepressor in the absence of DNA. To begin to examine
      the structural aspects of the arms that are responsible for these varied
      activities, we generated an extensive set of deletion and substitution mutants
      and measured the activities of these mutants in vivo using reporter gene fusions.
      Deletion of any part of the arms resulted in a significant decrease in repressor
      activity at both the trp and the trpR operons. Positions 4, 5 and 6 were the most
      sensitive to missense changes. Most substitutions at these positions resulted in
      repressors with less than 5% of the activity of the wild-type trp repressor. A
      large percentage of the missense mutants were more active than the wild-type
      repressor in medium containing tryptophan and less active in medium without
      tryptophan. This phenotype can be explained in terms of altered oligomerization
      of both the repressor and the aporepressor. Also, nine super-repressor mutants,
      resulting from substitutions clustered at both ends of the arms, were found. Our
      results support the hypothesis that the NH2-terminal arm of the trp repressor is
      a multifunctional domain and reveal structural components likely to be involved
      in the various functions.

PMID- 9570399
TI  - Flagellar filament elongation can be impaired by mutations in the hook protein
      FlgE of Salmonella typhimurium: a possible role of the hook as a passage for the
      anti-sigma factor FlgM.
AB  - Among motile revertants isolated from flagellar hook-deficient (flgE) mutants of
      Salmonella typhimurium, one produced only short flagellar filaments in L broth,
      despite the fact that flagellin itself has the ability to polymerize into long
      filaments in vitro. This pseudorevertant has an intragenic suppressor, resulting
      in a two-amino-acid substitution (Asp-Gln-->Ala-Arg) in the C-terminal region of
      the hook protein, FlgE. The flagellation of the pseudorevertant was greatly
      affected by the concentration of NaCl in the culture media: we observed no
      filaments in the absence of NaCl, short filaments in 1% NaCl and full-length
      filaments in 2% NaCl. Electron microscopy of osmotically shocked cells showed
      that the number of hook-basal bodies on cells was constant under various NaCl
      conditions. Furthermore, we found that the mutant hook was straight rather than
      curved. We monitored the cellular flagellin level of this pseudorevertant under
      various NaCl concentrations by immunoblotting. It was revealed that little
      flagellin was present under NaCl-free conditions in contrast with the ordinary
      amounts of flagellin present in 2% NaCl. As the expression of flagellin is
      regulated by competitive interaction of a sigma factor, FliA, and a corresponding
      anti-sigma factor, FlgM, we also observed the effect of NaCl on the secretion of
      FlgM. FlgM was secreted into the media in more than 1% NaCl but accumulated
      inside the cells in the absence of NaCl, indicating that the failure of secretion
      of FlgM in the absence of salt was the cause of the impaired elongation of
      filaments.

PMID- 9570400
TI  - Influence of FIS on the transcription from closely spaced and non-overlapping
      divergent promoters for an aminoacyl-tRNA synthetase gene (gltX) and a tRNA
      operon (valU) in Escherichia coli.
AB  - The gltX gene, encoding the glutamyl-tRNA synthetase (GluRS), and the valU
      operon, whose transcripts contain three tRNAVal/UAC and one tRNALys/UUU, are
      adjacent and divergently transcribed. It is the only known case of adjacent genes
      encoding an aminoacyl-tRNA synthetase and a tRNA precursor in Escherichia coli.
      The gltX promoters (P1, P2 and P3) direct the synthesis of transcripts non
      overlapping with and divergent from the one initiated at the valU promoter. We
      report that their promoter region (250 bp) contains three binding sites for the
      factor for inversion stimulation (FIS), centred at positions -71, -91 and -112
      from the valU transcription initiation site, and that the destruction of any of
      these sites does not prevent the binding of FIS to the others. As FIS is one of
      the major positive regulators of stable RNA operons, we have studied its role on
      gltX and valU transcription. FIS stimulates valU transcription in vitro and about
      twofold in vivo during steady-state exponential growth. In contrast, gltX
      transcription is repressed by the presence of FIS in vitro and about twofold in
      vivo during growth acceleration when a decrease in GluRS concentration was
      observed. Under all conditions tested, most of the gltX transcripts start at the
      P3 promoter. Nested deletions of this regulatory region reveal that the FIS
      dependent repression of the gltX-P3 promoter is abolished after the removal of
      the valU promoter, and is not altered by the additional removal of the FIS
      binding sites; moreover, in vivo transcription from gltX-P1 and/or gltX-P2
      present on some of these regulatory region variants is modulated by the nature of
      the upstream region by FIS and is sometimes stronger than that from gltX-P3.
      These results show that the strength and the site of gltX transcription
      initiation are influenced by the upstream region up to and including the valU
      promoter; furthermore, they indicate that although these adjacent genes are
      involved in the first step of protein biosynthesis and share cis and trans
      regulatory elements, their transcription is non-co-ordinate.

PMID- 9570401
TI  - A novel protein kinase that controls carbon catabolite repression in bacteria.
AB  - HPr(Ser) kinase is the sensor in a multicomponent phosphorelay system that
      controls catabolite repression, sugar transport and carbon metabolism in gram
      positive bacteria. Unlike most other protein kinases, it recognizes the tertiary
      structure in its target protein, HPr, a phosphocarrier protein of the bacterial
      phosphotransferase system and a transcriptional cofactor controlling the
      phenomenon of catabolite repression. We have identified the gene (ptsK) encoding
      this serine/threonine protein kinase and characterized the purified protein
      product. Orthologues of PtsK have been identified only in bacteria. These
      proteins constitute a novel family unrelated to other previously characterized
      protein phosphorylating enzymes. The Bacillus subtilis kinase is shown to be
      allosterically activated by metabolites such as fructose 1,6-bisphosphate and
      inhibited by inorganic phosphate. In contrast to wild-type B. subtilis, the ptsK
      mutant is insensitive to transcriptional regulation by catabolite repression. The
      reported results advance our understanding of phosphorylation-dependent carbon
      control mechanisms in Gram-positive bacteria.

PMID- 9570402
TI  - PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and
      polymyxin resistance.
AB  - Antimicrobial peptides are distributed throughout the animal kingdom and are a
      key component of innate immunity. Salmonella typhimurium regulates mechanisms of
      resistance to cationic antimicrobial peptides through the two-component systems
      PhoP-PhoQ and PmrA-PmrB. Polymyxin resistance is encoded by the PmrA-PmrB
      regulon, whose products modify the lipopolysaccharide (LPS) core and lipid A
      regions with ethanolamine and add aminoarabinose to the 4' phosphate of lipid A.
      Two PmrA-PmrB-regulated S. typhimurium loci (pmrE and pmrF) have been identified
      that are necessary for resistance to polymyxin and for the addition of
      aminoarabinose to lipid A. One locus, pmrE, contains a single gene previously
      identified as pagA (or ugd) that is predicted to encode a UDP-glucose
      dehydrogenase. The second locus, pmrF, is the second gene of a putative operon
      predicted to encode seven proteins, some with similarity to glycosyltransferases
      and other complex carbohydrate biosynthetic enzymes. Genes immediately flanking
      this putative operon are also regulated by PmrA-PmrB and/or have been associated
      with S. typhimurium polymyxin resistance. This work represents the first
      identification of non-regulatory genes necessary for modification of lipid A and
      subsequent antimicrobial peptide resistance, and provides support for the
      hypothesis that lipid A aminoarabinose modification promotes resistance to
      cationic antimicrobial peptides.

PMID- 9570403
TI  - A rolling circle replication initiator protein with a nucleotidyl-transferase
      activity encoded by the plasmid pGT5 from the hyperthermophilic archaeon
      Pyrococcus abyssi.
AB  - The plasmid pGT5 from the hyperthermophilic archaeon Pyrococcus abyssi presents
      similarities to plasmids from the pC194 family that replicate by the rolling
      circle mechanism. These plasmids encode a replication initiator protein, which
      activates the replication origin by nicking one of the two DNA strands. The gene
      encoding the putative Rep protein of pGT5 (Rep75) has been cloned and
      overexpressed in Escherichia coli, and the recombinant protein has been purified
      to homogeneity. Rep75 exhibits a highly thermophilic nicking-closing activity in
      vitro on single-stranded oligonucleotides containing the putative double-stranded
      replication origin sequence of pGT5. Gel shift analyses on single-stranded
      oligonucleotides indicate that Rep75 recognizes the single-stranded DNA region
      upstream of the nicking site via non-covalent interaction and remains covalently
      linked to the 5'-phosphate of the downstream fragment after nicking. Besides
      these expected activities, Rep75 contains a dATP (and ATP) terminal transferase
      activity at the 3'-OH extremity of the nicking site, which had not been reported
      previously for proteins of this type. Rep75, which is the first replication
      initiator protein characterized in an archaeon, offers an attractive new model
      for the study of rolling circle replication.

PMID- 9570404
TI  - The DevBCA exporter is essential for envelope formation in heterocysts of the
      cyanobacterium Anabaena sp. strain PCC 7120.
AB  - The gene devA of the filamentous heterocyst-form-ing cyanobacterium Anabaena sp.
      strain PCC 7120 encodes a protein with high similarity to ATP-binding cassettes
      of ABC transporters. Mutant M7 defective in the devA gene is arrested in the
      development of heterocysts at an early stage and is not able to fix N2 under
      aerobic conditions. The devA gene is differentially expressed in heterocysts. To
      gain a better understanding of the structural components of this putative ABC
      transporter, we determined the complete nucleotide sequence of the entire gene
      cluster. The two additional genes, named devB and devC, encode proteins with
      similarities to membrane fusion proteins (DevB) of several ABC exporters and to
      membrane-spanning proteins (DevC) of ABC transporters in general. Site-directed
      mutations in each of the three genes resulted in identical phenotypes. Heterocyst
      specific glycolipids forming the laminated layer of the envelope were identified
      in lipid extracts of M7 and in the site-directed mutants. However, transmission
      electron microscopy revealed unequivocally that the glycolipid layer is missing
      in mutant M7. Ultrastructural analysis also confirmed a developmental block at an
      early stage of differentiation. The results of this study suggest that the devBCA
      operon encodes an exporter of glycolipids or of an enzyme that is necessary for
      the formation of the laminated layer. The hypothesis is proposed that an intact
      envelope could be required for further heterocyst differentiation.

PMID- 9570405
TI  - Neisseria meningitidis producing the Opc adhesin binds epithelial cell
      proteoglycan receptors.
AB  - Neisseria meningitidis possesses a repertoire of surface adhesins that promote
      bacterial adherence to and entry into mammalian cells. Here, we have identified
      heparan sulphate proteoglycans as epithelial cell receptors for the meningococcal
      Opc invasin. Binding studies with radiolabelled heparin and heparin affinity
      chromatography demonstrated that Opc is a heparin binding protein. Subsequent
      binding experiments with purified 35SO4-labelled epithelial cell proteoglycan
      receptors and infection assays with epithelial cells that had been treated with
      heparitinase to remove glycosaminoglycans confirmed that Opc-expressing
      meningococci exploit host cell-surface proteoglycans to gain access to the
      epithelial cell interior. Unexpectedly, Opa28-producing meningococci lacking Opc
      also bound proteoglycans. These bacteria also bound CEA receptors in contrast to
      the Opc-expressing phenotype, suggesting that Opa28 may possess domains with
      specificity for different receptors. Opa/Opc-negative meningococci did not bind
      either proteoglycan or CEA receptors. Using a set of genetically defined mutants
      with different lipopolysaccharide (LPS) and capsular phenotype, we were able to
      demonstrate that surface sialic acids interfere with the Opc-proteoglycan
      receptor interaction. This effect may provide the molecular basis for the
      reported modulatory effect of capsule and LPS on meningococcal adherence to and
      entry into various cell types.

PMID- 9570406
TI  - Synthesis of Escherichia coli O9a polysaccharide requires the participation of
      two domains of WbdA, a mannosyltransferase encoded within the wb* gene cluster.
AB  - WbdA (previously MtfA) is one of the mannosyltransferases encoded within the
      Escherichia coli O9a wb* gene cluster. It is composed of two domains of similar
      size, connected by an alpha-helix chain. Elimination of the C-terminal half by
      transposon insertion or gene deletion caused synthesis of an altered structural O
      polysaccharide consisting only of alpha-1,2-linked mannose. O9a polysaccharide
      synthesis was restored by the C-terminal half of WbdA in trans. No membrane
      incorporation of mannose from GDP mannose was observed in a strain carrying only
      the gene for truncated WbdA. For mannose incorporation, it was necessary to
      introduce both wbdB and wbdC genes into the strain. Therefore, it is likely that
      the N-terminal half of truncated WbdA synthesizes the altered O-polysaccharide
      together with other mannosyltransferases which participate in the initial
      reactions of the O9a polysaccharide synthesis. Both N- and C-terminal domains of
      WbdA are required for the synthesis of the complete E. coli O9a polysaccharide.
      The chi sequence location between the two domains and homology plot analyses of
      the wbdA and the WbdA protein suggested that the wbdA gene might have arisen by
      fusion of two independent genes.

PMID- 9570407
TI  - Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium.
AB  - Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very
      potent against the tuberculous mycobacteria. It is about 100-fold less effective
      against Mycobacterium avium. This difference has often been attributed to a
      decreased permeability of the cell wall. We measured the rate of conversion of
      radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and
      estimated the permeability barrier imposed by the cell wall to INH influx in
      Mycobacterium tuberculosis and M. avium. There was no significant difference in
      the relative permeability to INH between these two species. However, the total
      conversion rate in M. tuberculosis was found to be four times greater.
      Examination of in vitro-generated mutants revealed that the major resistance
      mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of
      lipid and protein biosynthetic profiles demonstrated that the molecular target of
      activated INH was identical for both species. M. avium, however, formed colonies
      at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate
      deficient M. avium exhibited altered colony morphologies, modified cell wall
      ultrastructure and were 10-fold more sensitive to treatment with hydrophobic
      antibiotics, such as rifampin. These findings may significantly impact the design
      of new therapeutic regimens for the treatment of infections with atypical
      mycobacteria.

PMID- 9570408
TI  - The ClpC ATPase of Listeria monocytogenes is a general stress protein required
      for virulence and promoting early bacterial escape from the phagosome of
      macrophages.
AB  - Under stress conditions, the facultative intracellular pathogen Listeria
      monocytogenes produces a ClpC ATPase, which is a general stress protein encoded
      by clpC and belonging to the HSP-100/Clp family. A ClpC-deficient mutant was
      obtained by gene disruption in strain LO28, which became highly susceptible to
      stress conditions in vitro. Intracellular growth of this mutant was restricted
      within macrophages, one of the major target cells of L. monocytogenes, during the
      infectious process. A quantitative electron microscope study showed that,
      contrary to wild-type bacteria that rapidly gain access to the cytoplasm of
      macrophages, mutant bacteria remained confined to membrane-bound phagosomes. Only
      a few mutant bacteria disrupted the phagosome membrane after 4h of incubation,
      then polymerized actin filaments and multiplied within the cytoplasm. The ClpC
      ATPase, therefore, promotes early bacterial escape from the phagosome of
      macrophages, thus enhancing intracellular survival. The ClpC ATPase was produced
      in vivo during experimental infection by wild-type bacteria. The virulence of the
      ClpC-deficient mutant was severely attenuated in mice, with a three-log decrease
      in its 50% lethal dose compared with wild-type bacteria. Bacterial growth of
      mutant bacteria was strongly restricted in organs, presumably because of an
      impairment of intracellular survival in host tissues. Our results provide
      evidence that a general stress protein is required for the virulence of L.
      monocytogenes, which behaves as a virulence factor promoting intracellular
      survival of this pathogen.

PMID- 9570410
TI  - Channel or channel-like activity associated with pore-forming proteins or
      peptides?

PMID- 9570409
TI  - EspB and EspD require a specific chaperone for proper secretion from
      enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli uses a type III secretion apparatus to deliver
      proteins essential for pathogenesis to the host epithelium. Several proteins have
      been detected in culture supernatants of the prototype EPEC strain E2348/69 and
      three of these, EspA, EspB, and EspD, use type III machinery for export. Here, we
      report the identification and characterization of CesD, a protein required for
      proper EspB and EspD secretion. CesD shows sequence homology to chaperone
      proteins from other type III secretion pathways. Based on this, we hypothesize
      that CesD may function as a secretion chaperone in EPEC. A mutation in cesD
      abolished EspD secretion into culture supernatants and reduced the amount of
      secreted EspB, but had little effect on the amount of secreted EspA. The mutant
      strain was negative for both FAS and Tir phosphorylation, consistent with the
      previously described roles for EspB and EspD in EPEC pathogenesis. CesD was shown
      to interact with EspD but not EspB or EspA. CesD was detected in the bacterial
      cytosol, and, surprisingly, a substantial amount of the protein was also found to
      be associated with the inner membrane. Thus, although CesD has some attributes
      that are similar to other type III secretion chaperones, its membrane
      localization separates it from previously described members of this family.

PMID- 9570411
TI  - Laying down evidence of English skills.

PMID- 9570412
TI  - NCLEX-RN test plan update.

PMID- 9570413
TI  - The importance of critical thinking.

PMID- 9570414
TI  - Enabling student nurses to use the information superhighway.
AB  - Nursing graduates must be sophisticated in the use of information technologies
      and understand how these technologies interface with various health care systems.
      The purpose of this project was to evaluate the impact of a newly developed
      Internet course, focusing on current information technologies, on 20 RN-to-MSN
      students. Author-developed instruments were used to measure weekly computer use,
      perceived computer skill, and knowledge related to the information superhighway.
      The Stronge & Brodt Nurses Attitudes Toward Computerization Questionnaire was
      used to assess attitudes toward computerization. Qualitative data was elicited
      using weekly evaluation forms. When compared to 23 students at a similar stage of
      their nursing program, quantitative findings indicated that, at the end of the
      semester, students in the pilot course had more computer knowledge, reported
      greater computer skill, and used computers more. Qualitative findings suggested
      that pilot students: * Were connected with nursing networks and expressed their
      intent to maintain these networks. * Were able to use current health information
      found on the Internet in their nursing practices. * Used skills learned in the
      pilot class to complete projects in other classes. * Communicated with classmates
      via the Internet, thus forming a potentially valuable professional support
      system. * Used the library and librarians early in their programs. * Understood
      the relevancy of telemedicine and the Internet to the future survival of nursing
      in a changing health care arena. While the authors caution that an adequate
      infrastructure must be available to support such an endeavor, they emphasize that
      knowledge of the relevancy and use of the information superhighway is crucial to
      the future survival of nursing in a rapidly changing health care arena.

PMID- 9570415
TI  - Information science for the future: an innovative nursing informatics curriculum.
AB  - Health care is increasingly driven by information, and consequently, patient care
      will demand effective management of information. The report of the Priority
      Expert Panel E: Nursing Informatics and Enhancing Clinical Care Through Nursing
      Informatics challenges faculty to produce baccalaureate graduates who use
      information technologies to improve the patient care process and change health
      care. The challenge is to construct an evolving nursing informatics curriculum to
      provide nursing professionals with the foundation for affecting health care
      delivery. This article discusses the design, implementation, and evaluation of an
      innovative nursing informatics curriculum incorporated into a baccalaureate
      nursing program. The basic components of the curriculum framework are
      information, technology, and clinical care process. The presented integrated
      curriculum is effective in familiarizing students with informatics and
      encouraging them to think critically about using informatics in practice. The two
      groups of students who completed the four-course sequence will be discussed.

PMID- 9570416
TI  - Intuition in nursing practice: sharing graduate students' exemplars with
      undergraduate students.
AB  - Failure to acknowledge ways of knowing in nursing education curricula other than
      linear reasoning hinders the development of the full extent of mental abilities
      brought to learning situations by nursing students. Nurse educators are
      challenged to develop creative methods to facilitate nursing students' intuitive
      thinking. In this article, a teaching strategy is described in which graduate
      students' exemplars of intuition in clinical practice are shared with
      undergraduate nursing students. Implications of using this teaching approach to
      demystify the intuitive process and address its legitimacy are discussed.

PMID- 9570417
TI  - Choosing to write the paper format thesis.
AB  - Graduate students today may be faced with the option of writing either a
      traditional format thesis or a paper format thesis. In contrast to the
      traditional format in which the text body consists of four or five chapters, the
      body of the paper format thesis can be comprised of an introductory chapter, two
      or more papers written as publishable manuscripts, and a conclusion. In this
      article, an overview of the paper format thesis is presented and contrasted with
      the traditional format thesis. The description of the paper format thesis is
      followed by its advantages and disadvantages for writers and readers. It is by
      weighing all possible pros and cons, as well as considering one's individual
      situation, that the graduate student will be able to decide which format of
      thesis to write.

PMID- 9570418
TI  - Nurse practitioner education: living it, learning it.

PMID- 9570419
TI  - Developing business skills in health care: the experience of advanced practice
      nursing students.

PMID- 9570420
TI  - Factors influencing the publishing efforts of graduate students in nursing.
AB  - The purposes of this study were to identify factors influencing publication
      efforts of graduate students in nursing and determine the extent to which
      graduate students' scholarly activities contribute to the creation and
      dissemination of knowledge in nursing, as evidenced by publication in a
      professional journal. Authors of articles in Nursing Research were surveyed to
      assess their status as graduate students during the conceptualization,
      development, and publication of nursing research studies. The sample consisted of
      633 authors of manuscripts published in Nursing Research from 1987 to 1991. The
      study design was descriptive. A survey questionnaire elicited data on graduate
      student status and factors that influenced the initiation and completion of the
      project. The data were analyzed using descriptive statistical techniques. The
      results of the study suggest that graduate students in nursing make important
      contributions to the advancement and dissemination of nursing knowledge. Factors
      that influence graduate students to engage in the process include academic
      requirements (e.g., thesis, dissertation, coursework), faculty involvement and
      support, and the ability to self-select the research topic.

PMID- 9570421
TI  - Incorporating electronic-based and computer-based strategies: graduate nursing
      courses in administration.
AB  - The use of electronic technology allows faculty to improve their course
      offerings. Four graduate courses in nursing administration were contemporized to
      incorporate fundamental computer-based skills that would be expected of graduates
      in the work setting. Principles of adult learning offered a philosophical
      foundation that guided course development and revision. Course delivery
      strategies included computer-assisted instructional modules, e-mail interactive
      discussion groups, and use of the electronic classroom. Classroom seminar
      discussions and two-way interactive video conferencing focused on group
      resolution of problems derived from employment settings and assigned readings.
      Using these electronic technologies, a variety of courses can be revised to
      accommodate the learners' needs.

PMID- 9570422
TI  - Perceived benefits of peer leadership as described by junior baccalaureate
      nursing students.
AB  - Nursing students often do not get the chance to practice the skills they need as
      nurses prior to graduation. Many of the required skills are difficult to teach
      using traditional classroom or clinical teaching methods. Peer leadership is one
      teaching method that may provide alternative learning opportunities for enhancing
      these professional nursing skills, and it encompasses the notions of peer
      teaching and peer supervision simultaneously. The purpose of this study was to
      describe what junior baccalaureate nursing students perceived as the benefits of
      a peer leadership experience, using Loving's Competence Validation Model as the
      theoretical framework. Twelve junior nursing students participated during their
      adult medical-surgical rotation and completed self-evaluations following the peer
      leadership experience. From analysis of these self-evaluations, responses were
      categorized into five perceived benefits: practice in prioritizing, enhancement
      of critical thinking skills, enhancement of technical skills, realization of
      peers as resources, and development of management skills.

PMID- 9570423
TI  - Role of T channels in cardiovascular function.
AB  - Although two types of Ca2+ channels are found to occur in the cardiovascular
      system, very little is known about one of them, primarily because a
      pharmacological blocking agent has been lacking. The enigmatic transient (T)-type
      Ca2+ channel has finally been recognized by a selective Ca2+ antagonist. The
      novel tetralol Ca2+ antagonist, mibefradil, is a selective T-type Ca2+ channel
      blocker that produces effective vasodilatation with additional inhibitory actions
      on blood vessel wall and left ventricular thickening. The availability of a
      blocking agent has begun to reveal the significance of T-type Ca2+ channel
      signals. Selective T-type Ca2+ channel blockade characteristics include vascular
      selectivity, freedom from negative cardiac inotropism, consistent and predictable
      reduction in heart rate, reduction in subendothelial proliferation, and increased
      survival of severely hypertensive and heart failure animal models. Mibefradil
      increases coronary blood flow without increasing myocardial oxygen consumption,
      and by decreasing heart rate and thus time spent in diastole, improves
      subendocardial perfusion. Improved perfusion of the myocardial wall and lowered
      heart rate appear to normalize the underlying pathophysiological factors, improve
      heart failure, and provide long-term protection. Thus, T-type Ca2+ channel
      blockade offers significant new cardiovascular protective benefits, even in the
      presence of critical pathophysiological elements (i.e. increased heart rate and
      neurohumors in the presence of decreased ejection fraction and contractility)
      found in heart failure.

PMID- 9570424
TI  - Comparative pharmacological properties among calcium channel blockers: T-channel
      versus L-channel blockade.
AB  - Calcium antagonists are potent vasodilators and are widely used in the treatment
      of hypertension and angina pectoris. The currently available compounds belong to
      three classes: (1) dihydropyridines (e.g. nifedipine, amlodipine and felodipine),
      (2) phenylalkylamines (e.g. verapamil) and (3) benzothiazepines (e.g. diltiazem).
      The three classes differ in their pharmacological profile and safety. For
      example, verapamil and diltiazem lower heart rate, while dihydropyridines
      increase it or leave it unchanged. With most of the latter compounds, a marked
      activation of the sympathetic nervous system has been noted. Most compounds
      exhibit negative inotropic effects, particularly the first-generation molecules,
      which is disadvantageous in patients with impaired left-ventricular function. The
      most common side effects of these drugs are flushing, headache and edema. With
      verapamil, constipation may represent a problem in certain patients. Hence, in
      spite of a large number of calcium antagonists available, there remains a need
      for new compounds with enhanced efficacy and improved tolerability. A new
      compound should lack any negative inotropism, avoid any increase in sympathetic
      outflow or heart rate and exhibit a high degree of vascular selectivity.
      Furthermore, a low incidence of side effects, particularly ankle edema and
      optimal pharmacokinetics allowing once-daily dosing would be desirable.
      Mibefradil is a new calcium antagonist with promising pharmacological and
      clinical properties. The compound has a high bioavailability, lacks negative
      inotropic effects at therapeutic concentrations, does not exhibit reflex
      tachycardia during vasodilation and actually slightly decreases heart rate. It is
      a potent direct vasodilator efficacious in hypertension and chronic angina
      pectoris, elicits endothelium-dependent relaxations and facilitates the effects
      of nitric oxide in vascular smooth muscle. The drug is a particularly efficacious
      vasodilator in intramyocardial coronary arteries which may be important for its
      anti-ischemic effects and the lack of steal in the coronary circulation.
      Furthermore, mibefradil has antiproliferative properties in human vascular smooth
      muscle cells in culture. As a unique property, mibefradil blocks T-type calcium
      channels and hence represents a new class of calcium channel blockers. In
      patients with hypertension, mibefradil has a high efficacy in controlling blood
      pressure. The drug does not cause constipation and has a low incidence of ankle
      edema. A large trial is under way to further delineate the properties of this new
      calcium antagonist in patients with heart failure.

PMID- 9570425
TI  - Potential cardioprotective effect of mibefradil in the long-term treatment of
      hypertension.
AB  - During the last 2 decades, remarkable progress has been made in the treatment of
      hypertension with the discovery of new drugs lowering blood pressure by various
      mechanisms, e.g. calcium channel blockers, angiotensin-converting enzyme
      inhibitors and angiotensin II antagonists. These antihypertensive agents are now
      widely used as first-line therapy although there is still no definite proof that
      they have a cardioprotective effect and reduce the mortality rate in patients
      with coronary heart disease. Mibefradil is a new calcium antagonist with a novel
      mechanism of action since it is the only drug available so far able to block T
      channels. This compound might be particularly effective in preventing cardiac
      morbidity and mortality. It reduces heart rate when lowering blood pressure, has
      no negative inotropic effect, allows regression of cardiac hypertrophy and is
      effective in the treatment of angina. Mibefradil produces a sustained blood
      pressure reduction with a close to optimal trough:peak ratio. A major advantage
      of this novel compound is its excellent tolerability over the dose range
      recommended (50-100 mg/day). In particular, leg edema is seen clearly less often
      during mibefradil treatment than during therapy with dihydropyridines. Mibefradil
      has therefore an attractive profile in terms of both efficacy and safety and
      represents a promising first-line option to treat hypertensive patients.

PMID- 9570426
TI  - Anti-anginal and anti-ischemic effects of mibefradil, a new T-type calcium
      channel antagonist.
AB  - Mibefradil is the first of a new class of calcium antagonists (CAs), the tetralol
      derivatives, that selectively blocks the T-type calcium channel. The anti-anginal
      and anti-ischemic efficacy of mibefradil in patients with chronic stable angina
      pectoris was established in five placebo-controlled trials (2 monotherapy trials,
      3 trials with background beta-blocker or long-acting nitrate therapy). At the
      recommended doses of 50 and 100 mg, mibefradil treatment was associated with a
      significant dose-related increase in exercise test variables regardless of
      demographic subpopulation or background therapy. Significant reductions in weekly
      anginal attacks, silent ischemic parameters, heart rate (HR) and rate-pressure
      product were also observed. Two active-controlled trials compared mibefradil 100
      mg with amlodipine 10 mg or diltiazem SR 120 mg b.i.d., respectively. Patients
      receiving mibefradil showed significantly larger improvements than did those
      treated with amlodipine and similar improvements as those treated with diltiazem
      SR in all variables measured. In both studies, treatment with mibefradil was
      associated with a greater decrease in HR and rate-pressure product. Mibefradil
      was found to be well tolerated and safe; this held true for patients on chronic
      anti-anginal background therapy. The overall incidences of adverse events and
      premature withdrawals were only slightly higher than those of placebo-treated
      patients. Asymptomatic sinus bradycardia and first-degree atrioventricular block
      were the most frequently occurring mibefradil dose-related ECG changes.
      Mibefradil was better tolerated than amlodipine (mainly with regard to leg edema)
      and similarly well tolerated as diltiazem CD.

PMID- 9570427
TI  - Different effects of calcium antagonists in a rat model of heart failure.
AB  - Calcium antagonists have, to date, shown disappointing effect in chronic heart
      failure (CHF), possibly due to their cardiodepressant effects and/or reflex
      increases in sympathetic tone. Mibefradil is a new, selective T-channel calcium
      antagonist which has no relevant effects on cardiac contractility, sympathetic
      activity or neurohormonal levels. This study compares the effect of mibefradil
      with an angiotensin-converting enzyme (ACE) inhibitor on systemic and cardiac
      hemodynamics, cardiac structure and survival in a rat model of CHF. Rats
      underwent coronary artery ligation followed by 9 months treatment with
      mibefradil, cilazapril or no treatment. Both mibefradil and cilazapril increased
      survival rate to a similar extent over the study treatment period. Both periods
      reduced systolic blood pressure compared with untreated rats, although the
      reduction was slightly more marked with cilazapril than mibefradil. Both
      treatments decreased left ventricular (LV) end-diastolic and central venous
      pressures without any change in the first derivative LV pressure over time or
      heart rate. Mibefradil decreased LV weight without effecting right ventricular
      (RV) weight. Both drugs normalized LV collagen density. The data from this study
      show that long-term treatment with mibefradil results in a survival benefit
      comparable to that observed with an ACE inhibitor in a rat model of CHF.
      Mibefradil was also associated with improvements in cardiac hemodynamics, a
      reduction in LV weight and fibrosis. Mibefradil may be beneficial in the
      treatment of CHF.

PMID- 9570428
TI  - Calcium channel blockers in heart failure.
AB  - A considerable effort has been made in the last 15 years to evaluate the safety
      and efficacy of calcium channel blockers (CCBs) in the treatment of patients with
      chronic congestive heart failure (CHF). Available studies have provided strong
      evidence for a potential detrimental effect of the first-generation calcium
      antagonists in patients with CHF, indicating the need for great caution when
      these drugs are used in patients with significant depression of left ventricular
      systolic function. A number of second-generation CCB have demonstrated a strong
      vasodilatory effect and favorable hemodynamic action but failed to show a similar
      improvement in exercise capacity, morbidity and mortality. Moreover, drugs such
      as nicardipine and nisoldipine have resulted in a detrimental effect in some
      patients and, therefore, cannot be considered safe when used in patients with
      moderate-to-severe heart failure. Available information from the V-HeFT III study
      demonstrate a lack of an unfavorable effect of felodipine on exercise tolerance
      in patients with chronic heart failure. Although mortality rate was similar in
      both the felodipine and the placebo group, because of the relatively small number
      of patients in this study, no clear conclusion can be drawn regarding the effect
      of felodipine on mortality in patients with CHF. An encouraging signal regarding
      a potential role of CCB in the treatment of chronic heart failure has been
      provided by the recently completed PRAISE study. This prospective large-scale
      study demonstrated the safety of amlodipine, a long-acting dihydropyridine
      derivative, when used in patients with heart failure due to coronary artery
      disease. Furthermore, this study demonstrated a substantial reduction in
      mortality in patients with CHF due to nonischemic cardiomyopathy and provided a
      strong indication for a potential therapeutic benefit of amlodipine when added to
      standard CHF therapy in this patient population. No clear explanation is
      available at the present time regarding the reason for the deleterious effect
      demonstrated with some of the dihydropyridines and the contrasting benefit seen
      with amlodipine. Finally, more information regarding the safety and efficacy of
      dihydropyridines should become available in the next year. The PRAISE II study is
      ongoing and will provide further information regarding the therapeutic role of
      amlodipine in patients with nonischemic dilated cardiomyopathy. The MACH-1 study
      is evaluating the effect of mibefradil, a predominant T-type channel blocker with
      an ideal activity profile, on morbidity and mortality in patients with chronic
      CHF.

PMID- 9570429
TI  - Pain scoring--a method for assessing acute antianginal therapy comparison of the
      response to acute sublingual administration of an isosorbide dinitrate tablet,
      isosorbide dinitrate spray and nitroglycerin spray in unstable angina.
AB  - It is difficult to assess acute therapeutic intervention therapy, particularly in
      patients with unstable angina. Our aim was to evaluate the feasibility of a pain
      scoring method and to compare the response to sublingual administration of an
      isosorbide dinitrate (ISDN) tablet, ISDN spray or nitroglycerin (NTG) spray. Pain
      scoring was assessed by the subjective grading of the patients' pain severity
      from 1 to 10. We studied 205 patients (mean age 66 +/- 13 years). Pain
      attenuation, defined as at least 50% reduction in pain intensity, occurred in the
      ISDN tablet, ISDN spray and NTG spray groups after 360 +/- 290, 318 +/- 289 and
      233 +/- 271 s, respectively (p = 0.0005). In conclusion, pain scoring is a
      feasible and useful clinical method to assess antianginal therapy in unstable
      angina patients. Sublingual nitrate sprays, particularly NTG, seem to alleviate
      anginal pain faster than ISDN tablets in this patient population.

PMID- 9570430
TI  - Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in
      the human heart and the effects of spinal cord stimulation on pacing-induced
      angina pectoris.
AB  - Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and
      anti-ischemic effects in severe coronary artery disease. In the present study, 14
      patients were subjected to right-sided atrial catheterization and atrial pacing.
      The patients were paced to angina during a control session and during spinal cord
      stimulation. Myocardial extraction of beta-endorphin (BE) during control pacing
      (8 +/- 22%) changed to release at the maximum pacing rate during treatment (-21
      +/- 47%, a negative value representing release). Furthermore, the results
      indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene
      related peptide. In addition, it is implied that SCS may induce myocardial
      release of BE which could explain the beneficial effects in myocardial ischemia.

PMID- 9570431
TI  - Aortic intramural hematoma: an increasingly recognized aortic disease.
AB  - Aortic intramural hematoma (IMH) is a rarely diagnosed pathological condition
      that is not well characterized to date. We diagnosed IMH in 4 of 31 patients with
      suspected aortic dissection admitted to our coronary care unit from 1992 to 1995.
      In all 4 cases, IMH was located in the ascending aorta. At the time of
      hospitalization, all patients showed tachycardia, hypotension and pericardial
      effusion. Diagnosis of IMH was made by transesophageal echocardiography and
      computed tomography. We performed aortography in 2 patients, but it was non
      diagnostic in both of them. One patient died before surgery. Autopsy confirmed
      the diagnosis of IMH and showed severe pericardial effusion. In another patient,
      the diagnosis was confirmed during successful surgery, while the remaining 2
      patients recovered after medical therapy. The 3 surviving patients are still
      under follow-up control 12, 16 and 20 months after the initial acute event. We
      briefly discuss the epidemiological, clinical, diagnostic, therapeutic and
      prognostic aspects of IMH.

PMID- 9570432
TI  - Low serum cholesterol levels predict high perioperative mortality in patients
      supported by a left-ventricular assist system.
AB  - BACKGROUND: Although the use of a left-ventricular assist system (LVAS) provides
      circulatory support for end-stage heart failure patients awaiting heart
      transplantation, this procedure is accompanied by a relatively high perioperative
      mortality. The aim of this retrospective study was to identify those patients
      preoperatively which have the highest perioperative mortality. METHODS AND
      RESULTS: Forty-five consecutive patients undergoing LVAS implantation were
      evaluated for preoperative risk factors, including body mass index, hemodynamic
      data, and blood chemistry studies by multivariate analysis. They were divided
      into (1) patients who were successfully transplanted (n = 25) and (2) patients
      who died before transplantation (n = 20). The nonsurvivors were subclassified
      into patients who died within 14 days after surgery (n = 11) and patients who
      died after 2 weeks of device implantation (n = 9). Hemodynamic parameters were
      the same in both groups, but total cholesterol was significantly lower in the
      nonsurvivors than in the survivors (90 +/- 7 vs. 144 +/- 8 mg/dl, respectively, p
      < 0.0001). The sensitivity of predicting perioperative death with a serum
      cholesterol below 100 mg/dl was 100%, the specificity of predicting survival with
      a serum cholesterol above 120 mg/dl was 87%. CONCLUSION: In this small
      retrospective study, there was a correlation between total cholesterol levels and
      survival of patients with advanced heart failure on mechanical support. A
      cholesterol level below 100 mg/dl was accompanied by a high perioperative
      mortality. In contrast, a cholesterol level above 120 mg/dl was accompanied by a
      87% chance of survival. The results suggest a predictive value of cholesterol
      which is independent of the hemodynamic status.

PMID- 9570434
TI  - Downregulation of endothelin B receptors in cardiomyopathic hamsters.
AB  - The mechanisms responsible for abnormal fluid retention in congestive heart
      failure (CHF) are unclear. Studies were conducted to elucidate how endothelin
      (ET) may contribute to salt and water retention. Cardiomyopathic (CM) hamsters
      with moderate heart failure were employed for in vivo and in vitro trials.
      Clearance methods were used to compare the level of renal function in CM hamsters
      and control animals. Radioligand binding studies were also performed to determine
      ET receptor distribution in the inner medullary collecting ducts. CM hamsters
      exhibited an attenuated response to ANF infusion (FENa: 2.7 +/- 0.5 vs. 5.9 +/-
      0.8%, p < 0.01; FEH2O: 1.7 +/- 0.3 vs. 3.2 +/- 0.4%, p < 0.01; UcGMP: 11.2 +/-
      2.3 vs. 16.6 +/- 2.0 pmol/min, p < 0.05) and a decrease in total ET receptor
      density (532 +/- 77 vs. 959 +/- 154 fmol/mg protein, p < 0.005). Particularly ETB
      receptors were significantly reduced (214 +/- 26 vs. 483 +/- 88 fmol/mg protein,
      p < 0.003). Enalapril therapy simultaneously restored the natriuretic and
      diuretic effects of ANF and ET receptor density in the diseased animals. These
      studies suggest that the renin-angiotensin-aldosterone system and ET hormonal
      system act together, via ETB receptor downregulation, to promote the abnormal
      fluid retention observed in CHF.

PMID- 9570433
TI  - Effects of antioxidant vitamins C and E on atherosclerosis in lipid-fed rabbits.
AB  - BACKGROUND: Antioxidant vitamins are hypothesized to help prevent atherosclerosis
      by blocking lipoprotein oxidation. We investigated the effects of dietary
      vitamins C and E on atherosclerosis in rabbits. METHODS AND RESULTS: Forty New
      Zealand male rabbits were divided into 4 groups: 0.3% cholesterol diet with (LV)
      and without vitamin (LC), and 0.5% cholesterol diet with (HV) and without
      vitamins (HC). The treated groups consumed 137 +/- 8 mg/day vitamin C and 80 +/-
      4 mg/day vitamin E for 10 weeks. Vitamin treatment did not significantly affect
      serum lipids. Alpha-tocopherol values were significantly higher in both serum
      (mg/dl) and omental fat (microg/g) among the treated rabbits (3.9 +/- 0.5 and
      31.6 +/- 2.1 for LV, 1.7 +/- 0.2 and 12.1 +/- 1.9 for LC, 5.6 +/- 0.8 and 51.3 +/
      9.3 for HV and 1.9 +/- 0.3 and 8.2 +/- 0.4 for HC; p < 0.001). Vitamin treatment
      did not affect the percent of surface lesions in the aorta and pulmonary artery
      (23.8 +/- 5.2 and 20.1 +/- 3.3% for LV, 19.8 +/- 5.6 and 23.2 +/- 3.5% for LC,
      28.1 +/- 6.5 and 51.1 +/- 4.2% for HV and 32.4 +/- 5.5 and 43.7 +/- 3.9% for HC,
      respectively; p = 0.981 and p = 0.562. CONCLUSIONS: Although significantly higher
      values of alpha-tocopherol were found in both serum and omental fat, antioxidant
      vitamins C and E did not demonstrate a significant protective effect on
      atherosclerosis in lipid-fed rabbits during the 10-week study period.

PMID- 9570435
TI  - A prospective echocardiographic study of the effects of balloon mitral
      commissurotomy on pre-existing mitral regurgitation in patients with mitral
      stenosis.
AB  - Mitral regurgitation which is more than mild in severity is usually regarded as a
      relative contraindication to balloon mitral commissurotomy (BMC) because it is
      commonly believed that it may be worsened by the procedure. The aim of this study
      was to investigate the effects of BMC on pre-existing mitral regurgitation.
      Transthoracic and biplane transoesophageal echocardiography (TTE, TEE) combined
      with colour flow mapping (CFM) were performed prospectively on 50 consecutive
      patients immediately before and within 24 h after Inoue BMC. Before BMC, mitral
      regurgitation (MR) was diagnosed by TEE and left ventriculography in 36 and 13
      patients respectively. Angiographic MR was mild in all 13 cases. The precise
      origins of MR jets were carefully sought by scanning in multiple TTE and TEE
      views. The maximal area of colour flow MR jets detected by TEE was measured by
      planimetry. After BMC mean mitral valve area increased from 1.0 +/- 0.3 to 1.7 +/
      0.8 cm2, p < 0.0001, mean left atrial pressure and volume decreased from 23.7 +/
      5.6 mm Hg to 21.6 +/- 7.5 ml, p = 0.039, and from 105 +/- 56 to 90 +/- 46 ml, p
      = 0.002, respectively. MR jets as assessed by TEE CFM disappeared in 12 patients,
      in all of whom MR had been undetected by angiography. MR jets remained within 20%
      of their original sizes in 16 (44%) patients and more than doubled in only 3
      patients. However, the latter had only mild angiographic MR after BMC. BMC
      created new MR jets, distinct from pre-existing ones, in 27 (75%) patients. Their
      aetiologies were commissural splitting in 24, leaflet tears in 2 and chordal
      rupture in 1 case. New MR jets were co-existent with old jets in 17 (47%) cases
      and in 10 (28%) cases old jets were replaced by new jets. The severity of
      angiographic MR was unchanged in 21 (58%) of the 36 patients; new jets, all
      originating from one or both commissures, were found in 13 (65%) patients on TEE.
      Angiographic MR increased by 1 grade in 11 (33%) patients; new jets were detected
      in 9 patients, 8 from the commissures and 1 due to chordal rupture; in only 1 of
      the 11 patients did the increase in MR appear to be due to a worsening of a pre
      existing jet. Angiographic MR increased by 2 grades in 3 (8%) patients; new jets
      appeared in all 3, arising from the commissures in 2 and from a leaflet tear in 1
      case. One patient with a leaflet tear sustained an increase of 3 grades in
      angiographic MR. The final degree of angiographic MR was nil in 13, mild in 15,
      moderate in 6 and severe in 2 patients. Leaflet tears were responsible for both
      cases of severe MR. BMC does not appear to affect pre-existing mitral
      regurgitation adversely in almost all patients. It may abolish trivial jets but
      in most cases it creates new jets alongside the old ones. Leaflet tears are
      responsible for severe mitral regurgitation after BMC and this is independent of
      pre-existing regurgitant jets.

PMID- 9570436
TI  - Serial changes in atrial natriuretic peptide and endothelin-1 concentrations.
      Their relationships to the cardiac performance of patients hospitalized for acute
      myocardial infarction.
AB  - AIM: The study was designed to assess temporal changes in atrial natriuretic
      peptide (ANP) and endothelin-1 (ET) concentrations in patients hospitalized for
      acute myocardial infarction (AMI) and their relationships to cardiac performance
      determined by radionuclide ventriculography. PATIENTS AND METHODS: 20 patients
      with first AMI were studied. Blood samples were drawn within the first 4-18 h,
      after 18-24 h, and on days 2, 3 and 6. Plasma concentrations of ANP and ET were
      measured in blood samples taken simultaneously. Radionuclide ventriculography was
      performed on the day of discharge to determine left-ventricular ejection fraction
      (LVEF), left-ventricular end-diastolic volume index, end-systolic volume index
      and left-ventricular stroke volume index. RESULTS: Median concentrations of ET
      decreased from 2.15 pmol/l on admission to 1.45 pmol/l at discharge (32%, p <
      0.001). Median ANP rose from 29 to 79 pg/ml (172%, p < 0.001). The increment in
      ANP and the decrease in ET concentrations from admission to discharge was
      inversely correlated (r = -0.81, p < 0.005). ANP was inversely correlated to LVEF
      (r = -0.82, p < 0.001) and to the end-systolic volume index at discharge (r = 
      0.73, p < 0.003). CONCLUSION: Dynamic and inverse fluctuations in ET and ANP
      occur within the 1st week of AMI. The magnitude of endocrine activation in the
      ANP-ET system seems to reflect an impairment in the left-ventricular systolic
      performance.

PMID- 9570437
TI  - One-year mortality after acute myocardial infarction prior to and after the
      implementation of a widespread use of thrombolysis and aspirin. Experiences from
      the community of Goteborg, Sweden.
AB  - During 1 year of follow-up, we compared the mortality after acute myocardial
      infarction (AMI) prior to and after the introduction of a more widespread use of
      thrombolytic agents and aspirin. STUDY PERIOD: Two periods (I = 1986-1987 and II
      = 1989-1990) were compared. PATIENTS: All patients admitted to the coronary care
      units at the two city hospitals in the community of Goteborg who fulfilled the
      criteria for development of AMI participated in the evaluation. RESULTS: The
      overall 1-year mortality rate was 27% [corrected] during period I and 23% during
      period II (NS). However, among patients up to 70 years of age, the mortality was
      reduced from 15 to 11% (p < 0.05), whereas among patients aged over 70 years the
      mortality remained almost unchanged (34 vs. 35%; NS). CONCLUSION: The
      introduction of a more widespread use of thrombolytic agents and aspirin has not
      substantially changed the overall mortality in AMI. However, among younger
      patients, the mortality appears to have been reduced but not among the elderly.

PMID- 9570438
TI  - Clinical application of two novel rapid bedside tests for the detection of
      cardiac troponin T and creatine kinase-MB mass/myoglobin in whole blood in acute
      myocardial infarction.
AB  - The objective of this study was to determine whether two novel rapid bedside
      assays for whole-blood detection of cardiac troponin T and creatine kinase (CK)
      MB mass/myoglobin could rule out or rule in acute myocardial infarction in
      patients with acute chest pain. Ninety-two patients with chest pain <12 h prior
      to admission were investigated. No difference in the cumulative sensitivity of
      the TropT test and the CARDIAC STATus test (CK-MB mass and myoglobin in
      combination) was found 6 h after admission (94 vs. 97%). The cumulative positive
      predictive value of the TropT test and CARDIAC STATus test 6 h after admission
      was 97 and 76%, respectively. The negative predictive value was 97% for the TropT
      test and 98% for the CARDIAC STATus test at this time point. Our data show that
      the rapid assays provide diagnostic as well as prognostic information shortly
      after admission.

PMID- 9570439
TI  - Comparison of S-T segment/heart rate slope with exercise thallium imaging and
      conventional S-T segment criteria in detecting coronary artery disease: effect of
      exercise level on accuracy.
AB  - The S-T segment/heart rate (ST/HR) slope has been proposed as a more accurate
      electrocardiographic criterion for the diagnosis of coronary artery disease, but
      studies comparing the diagnostic value of the ST/HR slope with exercise thallium
      imaging are scant. The aims of this study were to assess the diagnostic accuracy
      of the ST/HR slope, conventional S-T segment criteria and exercise thallium
      imaging in detecting coronary artery disease and to evaluate the effect of
      exercise level on the sensitivity and specificity of these three techniques.
      Ninety consecutive patients underwent treadmill testing and exercise thallium
      single-photon emission computed tomography (SPECT) simultaneously. All 90
      patients also underwent coronary angiography within 1 month of the exercise test.
      We found that exercise thallium SPECT had a significantly higher diagnostic
      accuracy than either the ST/HT slope or conventional S-T segment criteria
      (thallium imaging 82%, ST/HR slope 67%, conventional S-T segment criteria 63%).
      The overall accuracy of the ST/HR slope was slightly but insignificantly greater
      than conventional S-T segment criteria (ST/HR slope 67%, conventional S-T segment
      criteria 63%; p = 0.639). In 50 patients with a lower exercise level, defined as
      not achieving 85% of their maximal predicted heart rate, the accuracy of the
      ST/HR slope was insignificantly greater (ST/HR slope 72%, conventional S-T
      segment criteria 66%; p = 0.517). In 40 patients with adequate exercise, the
      accuracy rate was the same (60%) for both the ST/HR slope and conventional S-T
      segment criteria. We conclude that exercise thallium imaging is more accurate
      than the ST/HR slope in diagnosing coronary artery disease and that the accuracy
      of the ST/HR slope is marginally better than conventional S-T segment criteria
      only in patients with a lower exercise level, and not in those with adequate
      exercise.

PMID- 9570440
TI  - Topographic pattern of advanced atherosclerotic lesions in carotid arteries.
AB  - Ulcers in extracranial carotid arteries are a known source of cerebral embolism.
      However, there are no data available on the prevalence of ulcerations located at
      the origin of these vessels in the aortic arch. Therefore, in this pathological
      study the topographic distribution of ulcerated lesions were determined in these
      arteries. One hundred and one consecutively autopsied patients composed the study
      group. Ulcerated plaques were sought for in both carotid arteries, from their
      origin in the arch up to the carotid canal, and also in the aortic arch and
      ascending aorta. The two anatomical sites mostly affected by atherosclerosis were
      the region of the carotid sinus and the orifices of cervical arteries in the
      aortic arch. More than one third of all ulcers were at the orifices of cervical
      arteries in the arch. Interestingly, ulcers at the orifice of the left common
      carotid artery in the arch were accompanied with other ulcers located elsewhere
      in the remaining segments of the left carotid system, whereas ulcerations at the
      orifice of brachiocephalic trunk were not accompanied with other concomitant
      lesions in the right carotid system. Furthermore, there was no symmetric
      distribution of ulcerated plaques in both carotid systems.

PMID- 9570441
TI  - Pharmacological modulation of cell adhesion molecules.
AB  - Cell adhesion molecules mediate the contact between two cells or between cells
      and the extracellular matrix. They are essential for morphogenesis, organization
      of tissues and organs, regulation of immune cell responses and migration of
      inflammatory cells from the blood vessels into inflamed tissues. Many diseases
      have been shown to be associated with dysfunction or with overexpression of
      certain adhesion molecules. Increased cell adhesion molecule function and number
      are found in clinical disorders in which inflammation and immune cells are
      involved. Several possible therapeutic agents are described here which have been
      shown to reduce the expression and/or function of cell adhesion molecules. Anti
      adhesion treatment can lead to diminished infiltration and activation of
      inflammatory immune cells resulting in decreased tissue injury and malfunction.

PMID- 9570442
TI  - Further studies on anti- and proconvulsant effects of inhibitors of nitric oxide
      synthase in rodents.
AB  - We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such
      as Nomega-nitro-L-arginine methyl ester and Nomega-nitro-L-arginine, differ
      depending on several experimental factors. Both compounds but not their less
      active enantiomers delayed picrotoxin-induced clonus in mice yet increased the
      incidence of clonus following low-dose picrotoxin. Nomega-nitro-L-arginine methyl
      ester significantly reduced the latencies of both myoclonus and clonus in older
      but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast,
      there was no significant change in the latencies for myoclonus and clonus in
      Wistar rats (older and younger). However, when pentylenetetrazol was administered
      i.p. rather than s.c., Nomega-nitro-L-arginine methyl ester dramatically
      increased latencies of convulsive indicators, including tonus, in both Sprague
      Dawley and Wistar rats. Nomega-nitro-L-arginine methyl ester also delayed tonus
      but not myoclonus or clonus in mice, regardless of the systemic route of
      administration of pentylenetetrazol. Both Nomega-nitro-L-arginine methyl ester
      and NG-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and
      Nomega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus.
      However, Nomega-nitro-L-arginine methyl ester reduced the tonic CD50 of both
      picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following
      maximal electroshock. Evidently, inhibitors of NO synthase are not universally
      effective antitonic drugs.

PMID- 9570443
TI  - Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced
      seizure in diazepam-withdrawn mice.
AB  - The decrease in the seizure threshold for pentylenetetrazole in diazepam
      withdrawn mice was not significantly affected by L-arginine (50 and 100
      microg/mouse, i.c.v.), which did have an antiseizure effect in chronically
      vehicle-treated mice. Sodium nitroprusside (25 and 50 microg/mouse, i.c.v.)
      increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn
      mice and chronically vehicle-treated mice. In addition, the antiseizure effect of
      L-arginine was blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L
      arginine (NOARG) and the NO scavenger, hemoglobin, while the effect of sodium
      nitroprusside was inhibited by hemoglobin, but not by NOARG, indicating that the
      antiseizure effect of L-arginine, but not that of sodium nitroprusside, is
      mediated by NO production resulting from the activation of NO synthase.
      Therefore, a decrease in the NO production via NO synthase may be involved in the
      hypersusceptibility to pentylenetetrazole during diazepam withdrawal.

PMID- 9570444
TI  - Alteration of alpha1-adrenoceptor subtypes in aortas of 12-month-old
      spontaneously hypertensive rats.
AB  - Alterations in alpha1-adrenoceptor subtypes in aortas from 12-month-old
      spontaneously hypertensive rats (SHR) were studied in functional studies and
      RNase protection assays. The norepinephrine-induced contraction, including
      maximum response and pD2 values, was not significantly different between the SHR
      and age-matched Kyoto Wistar (WKY) rats. The pA2 values of the alpha1D
      adrenoceptor subtype-selective antagonist BMY7378 (8-(2-(4-(2-methoxyphenyl)-1
      piperazinyl)ethyl)-8-azaspiro(4.5)dec ane-7,9-dionedihydrochloride) were
      increased from 8.10 +/- 0.12 in WKY rats to 8.45 +/- 0.13 in SHR (P < 0.05). The
      pA2 values of the alpha1A-adrenoceptor subtype-selective antagonist RS-17053 (N
      [2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dim ethyl-1H-indole-3
      ethanamine hydrochloride) were reduced from 8.52 +/- 0.20 in WKY rats to 7.82 +/-
      0.18 in SHR (P < 0.05), whereas the pA2 values of the alpha1A/alpha1D
      adrenoceptor subtype-selective antagonist WB4101 (2-(2,6-dimethoxphenoxyethyl)
      aminomethyl-1,4 benzodioxane) were not significantly different between WKY rats
      and SHR (9.05 +/- 0.22 versus 9.27 +/- 0.15, P > 0.05). Preincubation of
      preparations in 50 microM chloroethylclonidine for 30 min irreversibly inhibited
      the norepinephrine-induced response more profoundly in aortas from SHR than in
      aortas from WKY rats. The results of RNase protection assays showed that mRNAs
      for alpha1A- and alpha1B-adrenoceptor subtypes were decreased and that mRNA for
      the alpha1D-adrenoceptor subtype was increased in aortas from SHR compared with
      WKY rats. The results suggested that the alpha1A-adrenoceptor subtype was
      decreased and the alpha1D-adrenoceptor subtype was increased in aortas of 12
      month-old SHR.

PMID- 9570445
TI  - Acute and chronic haemodynamic effects of naftazone in portal hypertensive rats.
AB  - It has been demonstrated that hyperproduction of nitric oxide (NO) plays a major
      role in the vasodilatation of cirrhosis; thus, the vasodilatation might be
      reversed by an inhibition of NO production. Experimental studies in isolated
      aortic rings showed that naftazone inhibits the effects of NO production. The aim
      of this study was to evaluate the haemodynamic effects of acute and chronic
      administration of naftazone in rats with portal hypertension. Haemodynamic values
      were measured either before and 10 min after intravenous administration of 432
      microg/kg of naftazone or after 4 days of oral administration of 10 mg/kg per
      day. Acute administration of naftazone significantly reduced portal pressure in
      portal vein-stenosed and cirrhotic rats. This reduction was related to a decrease
      in the resistance of the liver and collateral circulation and it was associated
      with an increased cardiac output. Oral administration of naftazone significantly
      decreased portal pressure in rats with portal vein stenosis; this decrease
      depended on a significant reduction of portal blood flow. In both groups,
      arterial pressure did not change significantly. These haemodynamic effects
      differed from those observed following prazosin or propranolol administration.
      However, these effects were similar but less marked than those observed following
      N-nitro-L-arginine administration in systemic and splanchnic arterial
      territories. In conclusion, acute and oral administration of naftazone
      significantly reduces portal pressure by two different mechanisms in portal
      hypertensive rats. The exact mechanism has, however, to be elucidated.

PMID- 9570446
TI  - Effects of terbogrel on platelet function and prostaglandin endoperoxide
      transfer.
AB  - The present study describes the platelet-inhibitory effects of terbogrel (5
      hexenoic acid, 6-[3-[[(cyanoamino)[(1,1-dimethylethyl)amino]methylene]amino]pheny
      l]-6-(3-pyridinyl)-, (epsilon)-), a novel combined thromboxane A2 synthase
      inhibitor and thromboxane A2 receptor antagonist. Terbogrel concentration
      dependently inhibited collagen (0.6 microg/ml)- and U46619 (11alpha,9alpha
      epoxymethano-15(S)-hydroxy-prosta-5Z,+ ++13E-dienoic acid) (1 microM)-induced
      aggregation and thromboxane synthesis of washed human platelets. In this system,
      terbogrel exhibited an equipotent (IC50 of about 10 nM) activity as thromboxane
      A2 synthase inhibitor and thromboxane A2 receptor antagonist. In addition, the
      compound favoured prostacyclin synthesis in cultured vascular smooth muscle cells
      by increasing the transfer of platelet-derived prostaglandin endoperoxides.
      Terbogrel appears to be a compound with an equipotent molar potency as
      thromboxane A2 synthase inhibitor and receptor antagonist.

PMID- 9570447
TI  - Cilostazol, a selective cAMP phosphodiesterase inhibitor, dilates retinal
      arterioles and increases retinal and choroidal blood flow in rats.
AB  - The effects of cilostazol, a selective cyclic AMP (cAMP) phosphodiesterase
      inhibitor, on retinal and choroidal blood flow and retinal arteriole diameter
      were examined in anesthetized rats. The retinal and choroidal blood flow was
      measured using laser Doppler flowmetry, and the diameter of the retinal
      arterioles was measured using digital video microscopy. Cilostazol was
      administered by two routes; systemically via the intravenous route, and directly
      into the retinal vessels via the intra-arterial route. When administered
      intravenously, 1 mg/kg of cilostazol produced a biphasic blood flow response,
      composed of an initial decrease which was dependent on a depressor response of
      mean arterial pressure, and a subsequent slight but significant increase which
      was independent of changes in mean arterial pressure. When administered intra
      arterially over a 2-min period, 40-55 and 400-440 microg of cilostazol both
      produced an increase in the blood flow in a dose-dependent manner, while a
      depressor effect was observed only at the dose of 400-440 microg. The diameter of
      the retinal arterioles was increased after the intra-arterial injection of
      cilostazol (400 microg). It is concluded that intra-arterially administered
      cilostazol induces vasodilation of the retinal arterioles of rats, which results
      in an increase in blood supply to the retina, independent of changes in mean
      arterial pressure.

PMID- 9570448
TI  - Effects of endothelin-1 on norepinephrine-induced vasoconstriction in
      deoxycorticosterone acetate-salt hypertensive rats.
AB  - We investigated the effects of endothelin-1 on pressor responses to
      norepinephrine in perfused mesenteric arteries of deoxycorticosterone acetate
      (DOCA)-salt hypertensive rats. The response to norepinephrine (10(-6) M) was
      significantly increased in DOCA-salt rats compared with that in uninephrectomized
      control rats. Perfusion of the arteries with subpressor dose of endothelin-1 (3 x
      10(-10) M) for 15 min markedly enhanced the pressor responses to norepinephrine
      (10(-6) and 3 x 10(-6) M) in control rats and this effect was significantly
      prevented by BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D 
      1-methoxycarbonyl-tryptophanyl-D-norleucine] (10(-6) M), but not by FR139317
      ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-+
      ++methylpentanoyl]amino-3-[3-(1-methyl-1H-indoyl)]propionyl]ami no-3-(2
      pyridyl)propionic acid) (10(-6) M). In DOCA-salt hypertensive rats, increased
      pressor response to norepinephrine was declined to the level of control rats by
      BQ788, but not by FR139317. In contrast to the case seen with control rat,
      exogenous endothelin-1 had little effect on pressor responses to norepinephrine
      in the arteries of DOCA-salt hypertensive rats. Total immunoreactive endothelin
      content in the arteries of DOCA-salt hypertensive rats was significantly higher
      than that of uninephrectomized control rats. These results suggest that
      endothelin-1 enhances contractile responses to norepinephrine through endothelin
      ETB receptor. Moreover, this phenomenon is stimulated tonically by endogenous
      endothelin-1 in DOCA-salt hypertensive rats and may contribute to the maintenance
      of hypertension in DOCA-salt rats.

PMID- 9570449
TI  - Effects of phosphodiesterase inhibitors and salbutamol on microvascular leakage
      in guinea-pig trachea.
AB  - The aim of this study was to investigate the effects of selective
      phosphodiesterase inhibitors and their combination with salbutamol on antigen
      induced microvascular leakage in the trachea. In actively sensitized
      anaesthetized guinea-pigs, the non-selective phosphodiesterase inhibitor
      theophylline (100 mg/kg p.o.) and the selective phosphodiesterase type 4
      inhibitor Ro 20-1724 (30 mg/kg p.o.) inhibited antigen-induced microvascular
      leakage (-73.8% and -44.1%, respectively) as demonstrated by a reduced
      extravasation of plasma proteins measured by the use of Evans blue dye. No
      significant reduction in microvascular leakage was seen with (a) the selective
      phosphodiesterase type 4 inhibitor rolipram (10 mg/kg p.o.), (b) the selective
      phosphodiesterase type 3 inhibitors milrinone (30 mg/kg p.o.) and SK and F 94-836
      (30 mg/kg p.o.) or (c) the selective phosphodiesterase type 1/5 inhibitor
      zaprinast (30 mg/kg p.o.). Neither Ro 20-1724 nor rolipram and theophylline
      inhibited microvascular leakage induced by either substance P or histamine.
      Pretreatment with aerosolized salbutamol (10 microg/ml) potentiated the
      inhibitory effects of theophylline (-49.8% at 30 mg/kg p.o.) and Ro 20-1724 (
      52.6% at 10 mg/kg p.o.) versus antigen-induced microvascular leakage.
      Furthermore, a significant inhibitory effect of rolipram (10 mg/kg, p.o.) was
      obtained following pretreatment with this concentration of aerosolized
      salbutamol. Even at higher concentrations (0.3-2 mg/ml) salbutamol did not
      augment the corresponding inhibitory effects of rolipram and Ro 20-1724 versus
      microvascular leakage induced by either histamine or substance P. Theophylline
      had no effect versus substance P-induced microvascular leakage, but did inhibit
      it significantly (P < 0.05) after pretreatment with aerosolized salbutamol (0.3
      mg/ml). The potentiation by salbutamol of the inhibitory effects of both non
      selective and selective phosphodiesterase type 4 inhibitors versus antigen
      induced microvascular leakage probably results from a synergistic reduction in
      the release of anaphylactic mediators.

PMID- 9570450
TI  - Cannabinoid modulation of intestinal propulsion in mice.
AB  - The effect of cannabinoid receptor activation and blockade on the propulsive
      activity in the mouse small intestine was assessed in the present study by
      measuring the transit of an orally administered, non-absorbable marker. The
      cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl
      3[(morpholinyl)methyl]pyrrolo[1,2,3-de-1, 4benzoxazin-yl]-(1
      naphthalenyl)methanone mesylate) inhibited, while the selective cannabinoid CB1
      receptor antagonist SR 141716A (N-piperidino-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-3-pyraz ole-carboxamide) stimulated the marker transit.
      Furthermore, a per se non-effective dose of SR 141716A reversed WIN 55,212-2
      induced reduction of the transit. The results of the present study suggest a role
      for cannabinoid CB1 receptors in the control of propulsive activity in the mouse
      small intestine.

PMID- 9570451
TI  - Differential effect of indomethacin and ketorolac on postoperative ileus in rats.
AB  - The effect of two prostaglandin biosynthesis inhibitors and their interaction
      with the L-arginine/nitric oxide (NO) pathway was investigated in a rat model of
      experimental ileus. The gastrointestinal transit was measured as the migration of
      Evans blue after three different operations. Indomethacin completely reversed the
      additional inhibition of the transit induced by mechanical stimulation of the
      gut. Ketorolac completely reversed the inhibition of the transit induced by the
      laparotomy, but had no additional effect on the inhibition induced by mechanical
      stimulation of the gut. Administration of indomethacin plus L-nitroarginine or L
      arginine could not enhance or prevent the effect of indomethacin alone.
      Administration of ketorolac and L-nitroarginine completely reversed the transit
      after the laparotomy plus manipulation whereas ketorolac plus L-arginine had no
      additional effect as compared to ketorolac alone. From these findings we conclude
      that in addition to NO, prostaglandins are involved in the pathogenesis of
      postoperative ileus in the rat. However, indomethacin and ketorolac
      differentially affect postoperative ileus suggesting that prostaglandins are
      involved in different pathogenic mechanisms leading to postoperative ileus.

PMID- 9570452
TI  - Comparison between the insulinotropic potential of ten new esters of succinic
      acid.
AB  - Selected esters of succinic acid are currently under investigation as
      insulinotropic tools for the treatment of non-insulin-dependent diabetes
      mellitus. The aim of the present study was to investigate, in isolated rat
      pancreatic islets, the insulin secretory response to ten novel esters of succinic
      acid. According to six different methods of comparison, the following hierarchy
      in insulinotropic potential was established: 4-tert-butyl-succinate < or =
      glycerol-1,2-dimethylsuccinate-3-hydrogenosuccinate < or = threitol-3-succinoyl
      1,2,4-trimethylsuccinate < or = ethanediol-1,2-diethylsuccinate < or = glycerol
      1,2-dimethylsuccinate < or = glycerol-3-hydroxy-1,2-dimethylsuccinate < or =
      arabitol-5-hydroxy-1,2,3,4-tetramethylsuccinate < or = threitol-1,2,4
      trimethylsuccinate < or = ethanediol-1,2-dimethylsuccinate < propanediol-1,2
      dimethylsuccinate. There was a close correlation (r = 0.823) between the
      insulinotropic potential and the minimal effective concentration, which ranged
      between the extreme values of 10 microM and 2.5 mM. In the presence of the
      esters, the concentration-response relationship for glucose-stimulated insulin
      release was changed from its typically sigmoidal shape to a hyperbolic pattern,
      with most agents enhancing insulin output at a low hexose concentration (2.8 mM)
      but failing to do so at a high glucose level (16.7 mM). Highly potent
      insulinotropic esters have several advantages over other antidiabetic agents in
      clinical use.

PMID- 9570453
TI  - Prostaglandin E1 suppresses tumor necrosis factor-alpha and interleukin-10
      production by lipopolysaccharides-stimulated mononuclear cells.
AB  - Prostaglandin E1 has been clinically used in a variety of vascular occlusive
      diseases. We investigated the in vitro effect of prostaglandin E1 on the
      synthesis of tumor necrosis factor-alpha, interleukin-1, interleukin-6,
      interleukin-10 and transforming growth factor beta by human peripheral blood
      mononuclear cells stimulated with lipopolysaccharides. Prostaglandin E1
      significantly suppressed both the mRNA expression and the production of tumor
      necrosis factor-alpha and interleukin-10 by lipopolysaccharides-stimulated
      peripheral blood mononuclear cells in a dose-dependent manner (1 x 10(-6)-1 x 10(
      8) M). Since tumor necrosis factor-alpha is a potent proinflammatory cytokine
      involved in certain inflammatory diseases, our findings suggest the possibility
      to expand the clinical application of prostaglandin E1.

PMID- 9570454
TI  - Glucocorticoids reduce tachykinin NK2 receptor expression in bovine tracheal
      smooth muscle.
AB  - Neurokinin A is not only a potent bronchoconstrictor, but also has immuno
      modulatory effects in animals and man, mediated via tachykinin NK2 receptors. We
      have examined the effect of the glucocorticoid, dexamethasone, on tachykinin NK2
      receptor mRNA and the number of tachykinin NK2 receptors in bovine tracheal
      smooth muscle in vitro by Northern blot analysis using a human tachykinin NK2
      receptor cDNA probe and receptor binding assay using [3H]SR48968 [(S)-N-methyl
      N[4-acetylamino-4-phenylpiperidino-2(3,4-dichlorophenyl) butyl]benzamide].
      Tachykinin NK2 receptor mRNA showed a time-dependent suppression (62% reduction
      after 6 h at 10(-7) M of dexamethasone), as well as a concentration-dependent
      suppression after the incubation with dexamethasone (IC50 = 1.3 x 10(-8) M). This
      suppression was abolished by the glucocorticoid receptor antagonist, mifepristone
      (RU38486), indicating that dexamethasone acts via the glucocorticoid receptor. It
      was also abolished by the protein synthesis inhibitor, cycloheximide (10
      microg/ml), indicating that new protein synthesis is required on this
      suppression. Using the RNA polymerase inhibitor actinomycin D (5 microg/ml), we
      showed that the stability of tachykinin NK2 receptor mRNA was not affected by
      dexamethasone (t1/2 = 5 h). Nuclear run-on assays revealed a 51% reduction in the
      rate of tachykinin NK2 receptor gene transcription after treatment with
      dexamethasone for 6 h. Radioligand binding assay using an selective tachykinin
      NK2 receptor antagonist, [3H]SR48968 showed a significant decrease in the number
      of receptor binding sites after 16 h (Bmax = 262 +/- 23 versus 213 +/- 13 fmol/mg
      protein for vehicle and dexamethasone treatment respectively, P < 0.05), with no
      significant change at the earlier time points. These results suggest that
      glucocorticoids act on glucocorticoid receptors to decrease tachykinin NK2
      receptor expression by decreasing the rate of tachykinin NK2 receptor gene
      transcription.

PMID- 9570456
TI  - A novel recognition site for somatostatin-14 on the GABA(A) receptor complex.
AB  - Functional interactions between gamma-aminobutyric acid (GABA) and somatostatin
      are suggested by the presence of synaptic contacts between GABA and somatostatin
      neurons, colocalisation of GABA and somatostatin and reciprocal modulation of
      somatostatin and GABA release. Nevertheless, a direct interaction of somatostatin
      with the GABA(A) receptor complex has not yet been investigated. A quantitative
      autoradiographic technique was used to determine the ability of somatostatin to
      interact with the [35S]t-butylbicyclophosphothionate [35S]TBPS binding sites of
      the GABA(A) receptor complex: somatostatin inhibited [35S]TBPS binding with IC50
      values in the micromolar range in all brain regions studied. These results
      demonstrate for the first time a direct interaction between somatostatin and the
      GABA(A) receptor complex.

PMID- 9570455
TI  - Nipradilol inhibits DNA synthesis by regulating nitric oxide synthesis in
      cultured rat mesangial cells.
AB  - To elucidate whether nipradilol modulates mesangial cell function, we assessed
      the effects of nipradilol on DNA synthesis in the presence and absence of N-nitro
      L-arginine methyl ester (L-NAME) in cultured rat mesangial cells stimulated with
      1% fetal bovine serum. Nipradilol inhibited [3H]thymidine incorporation into
      mesangial cells in a dose- and time-dependent manner. In addition, the anti
      mitogenic effect of 100 microM nipradilol was significantly inhibited in the
      presence of 10 microM L-NAME. Moreover, nipradilol increased intracellular cyclic
      guanosine monophosphate (cGMP). These results suggest that nipradilol exerts its
      efficacy in the treatment of several types of glomerulonephritis with mesangial
      cell proliferation by increasing in intracellular cGMP.

PMID- 9570457
TI  - Place conditioning with the dopamine D1-like receptor agonist SKF 82958 but not
      SKF 81297 or SKF 77434.
AB  - While self-administration and place conditioning studies have shown that dopamine
      D2-like receptor agonists produce reward-related learning, the effects of
      dopamine D1-like receptor agonists remain equivocal. The present study tested
      three dopamine D1-like receptor agonists for their ability to induce a place
      preference. Like control rats treated with amphetamine (2.0 mg/kg i.p.), rats
      treated with SKF 82958 (+/- -6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5
      tetrahydro-1-phenyl-1H- 3-benzazepine hydrobromide; 0.05 but not 0.01, 0.025,
      0.075, or 0.10 mg/kg s.c. and/or i.p.) during conditioning showed a significant
      increase in the amount of time spent on the drug-paired side during the drug free
      test. Neither SKF 81297 (+/- -6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro
      1H-3-benzazepine hydrobromide; 0.25, 0.50, 1.0, 2.0, and 4.0 mg/kg i.p.) nor SKF
      77434 (+/- -7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride; 0.20, 1.0, 5.0, and 10.0 mg/kg i.p.) produced place conditioning.
      Significant increases in locomotion were seen at some doses of all drugs. Results
      show for the first time that systemic administration of a dopamine D1-like
      receptor agonist produces a place preference and are consistent with previous
      findings showing that dopamine D1-like receptor activation produces reward
      related learning.

PMID- 9570458
TI  - Opioid receptor agonists and antagonists alter GBR12909-induced turning in the
      rat.
AB  - We extended observations on cocaine-induced turning and its interactions with mu
      opioid receptor agonists in nigrally-lesioned rats to GBR12909 (1-[2-[bis(4
      fluorophenyl)methoxy]ethyl]-4-[3-phenyl-propyl]-piperazine) , a selective
      dopamine reuptake inhibitor. GBR12909 produced turning that was potentiated by
      the mu-opioid receptor agonists morphine and methadone. The effects of these
      opioids were blocked by the general opioid receptor antagonist naloxone, which
      did not affect the action of GBR12909. The reuptake inhibitors nisoxetine
      (norepinephrine) and fluoxetine (serotonin) did not produce turning alone or in
      combination with morphine. Antagonists selective for each opioid receptor subtype
      did not alter GBR12909-induced turning. However, naltrexone, another general
      opioid receptor antagonist, potentiated turning induced by GBR12909. This was
      blocked by naloxone, suggesting that naltrexone has opioid receptor agonist
      actions, in contrast to naloxone. These results indicate that cocaine-induced
      turning and its potentiation by mu-opioid receptor agonists are dependent upon
      the inhibition of dopamine reuptake.

PMID- 9570459
TI  - TRH receptor agonists ameliorate 3-acetylpyridine-induced ataxia through NMDA
      receptors in rats.
AB  - The effects of thyrotropin-releasing hormone (TRH) receptor agonists were
      examined on 3-acetylpyridine-induced cerebellar ataxia in rats. 3-acetylpyridine
      markedly decreased the maximal height of vertical jump, accompanied by motor
      incoordination. Both TA-0910 ((-)-N-[(S)-hexahydro-1-methyl-2,6-dioxo-4
      pyrimidinylcarbonyl]-L- histidyl-L-prolinamide tetrahydrate; 0.3-3 mg/kg), a
      novel TRH analog, and TRH (10 and 30 mg/kg) significantly increased the
      suppressed maximal height of vertical jump after single intraperitoneal
      administration. The effects of these drugs reached a maximum at 1 h and
      disappeared 24 h after administration. Both the TA-0910 (1 mg/kg)- and TRH (10
      mg/kg)-induced increases in the maximal height of vertical jump were completely
      counteracted by pretreatment with i.p. injected MK-801 (10,11-dihydro-5-methyl-5H
      dibenzo[a,d]cyclohepten-5,10-imine maleate; 0.1 mg/kg), an NMDA receptor
      antagonist. Neither bicuculline, muscimol, baclofen, cyproheptadine nor prazosin
      affected the effect of the TRH receptor agonists. In conclusion, TA-0910 is more
      potent than TRH in ameliorating cerebellar functional disorders. The anti-ataxic
      effects of these TRH receptor agonists may be mediated by NMDA receptors in 3
      acetylpyridine-treated rats.

PMID- 9570460
TI  - Modulation of phencyclidine-induced changes in locomotor activity and patterns in
      rats by serotonin.
AB  - To test the hypothesis that serotonergic modulation of the effects of
      phencyclidine (PCP) are due to circuit- rather than receptor-based interactions
      between glutamatergic and serotonergic systems, multivariate profiles of rat
      behavior were assessed after treatments with the 5-hydroxytryptamine (5-HT) 5-HT2
      receptor antagonist ketanserin (1.0 mg/kg), the 5-HT2 receptor agonist (1(2,5
      dimethoxy-4-iodophenyl)-2-aminopropane) (DOI; 0.27 mg/kg), various doses of PCP
      (0.75 to 10.125 mg/kg), or combinations thereof. Ketanserin blocked all effects
      of DOI, but reduced the effects of PCP only on locomotion. Depending on the dose,
      PCP was observed to increase or decrease locomotion and the roughness of the
      rats' patterns of locomotion. In any case, DOI always increased the activity and
      decreased the roughness of locomotor paths in PCP-treated rats. Thus, co
      administration of DOI and PCP did not yield a shift in the dose-effect curve for
      either drug, but instead resulted in a new behavioral profile consistent with a
      circuit-based dynamic interaction.

PMID- 9570461
TI  - Antagonistic effects of beta-phenylethylamine on quinpirole- and (-)-sulpiride
      induced changes in evoked dopamine release from rat striatal slices.
AB  - To assess the role of beta-phenylethylamine in aspects of dopamine release, we
      measured the level of beta-phenylethylamine in the rat striatum after killing the
      rats by microwave irradiation. We then investigated the effect of beta
      phenylethylamine on electrically evoked dopamine release from rat striatal slices
      in vitro. The striatal beta-phenylethylamine level was 46.5 +/- 3.5 ng/g wet
      tissue, equivalent to 0.3 micromol/l. Superfusion with low concentrations of beta
      phenylethylamine up to 1 micromol/l had no effect on spontaneous or electrically
      evoked dopamine release from striatal slices. Quinpirole reduced the evoked
      dopamine release from slices in a concentration-dependent manner. The quinpirole
      induced reduction of evoked dopamine release was attenuated 30% by superfusion
      with 0.3 micromol/l beta-phenylethylamine. Moreover, the (-)-sulpiride (0.1
      micromol/l)-induced increase in evoked dopamine release was also attenuated by
      superfusion with 0.3 micromol/l beta-phenylethylamine. These data indicate that
      submicromolar levels of beta-phenylethylamine could modify the dopamine
      autoreceptor mediated changes in evoked dopamine release from rat striatal
      slices.

PMID- 9570462
TI  - Muscarinic receptor subtypes in the rat prostate gland.
AB  - Muscarinic receptor subtypes mediating carbachol-induced contractions of the rat
      prostatic smooth muscle were determined. The rank order of potency of muscarinic
      receptor antagonists in blocking the effects of carbachol was (mean pKB estimates
      in parentheses): atropine (8.90) >> para-fluorohexahydrosiladifenidol (7.75) > or
      = hexahydrosiladifenidol (7.62) > methoctramine (6.89) > or = pirenzepine (6.68)
      > or = himbacine (6.67). The specific binding of [3H]quinuclidinyl benzilate to
      the rat prostatic homogenates was competitively inhibited by (mean pKi values in
      parentheses): atropine (8.89) >> hexahydrosiladifenidol (7.86) > para
      fluorohexahydrosiladifenidol (7.28) > or = himbacine (7.22) > pirenzepine (6.63)
      > or = methoctramine (6.38). These profiles, whilst different, indicate the
      probable involvement of muscarinic M3 receptors in the carbachol-induced
      contraction.

PMID- 9570463
TI  - A role of nitric oxide in WIN 55,212-2 tolerance in mice.
AB  - The role of nitric oxide (NO) in the development of cannabinoid tolerance was
      examined by using N(omega)-nitro-L-arginine methyl ester (L-NAME) as an inhibitor
      of NO synthase. R(+)-[2,3-Dihydro-5-methyl-3 [(morpholinyl)methyl]pyrrolo[1,2,3
      de]-1,4-benzoxazin-yl]-(1-napht halenyl)methanone mesylate (WIN 55,212-2), a
      cannabinoid receptor agonist, or L-NAME plus WIN 55,212-2 was acutely or
      chronically injected i.p. to mice and analgesia, body temperature and immobility
      were measured. A single injection of WIN 55,212-2 induced time- and dose
      dependent analgesia, hypothermia and catalepsy. L-NAME (50 mg/kg), which per se
      was ineffective, administered 20 min before WIN 55,212-2 did not modify the
      analgesic, hypothermic and cataleptic responses to the cannabinoid. When WIN
      55,212-2 was administered once a day, the animals became completely tolerant to
      the analgesic, hypothermic and cataleptic effects within five, seven and nine
      days respectively. L-NAME injected once daily 20 min before WIN 55,212-2
      inhibited the development of tolerance to the hypothermic and cataleptic actions
      but not to the analgesic action of WIN 55,212-2. Since L-NAME given chronically
      by itself did not modify the analgesia, hypothermia and catalepsy induced by
      acute administration of WIN 55,212-2, our findings suggest L-NAME acts with some
      selectivity on the mechanisms involved in cannabinoid tolerance.

PMID- 9570464
TI  - Effects of idazoxan on dopamine release in the prefrontal cortex of freely moving
      rats.
AB  - To clarify the involvement of dopaminergic neuronal systems in anxiety or fear,
      the present study was undertaken to elucidate the effect of an anxiogenic agent,
      idazoxan, a selective alpha2-adrenoceptor antagonist, on dopamine release from
      the rat prefrontal cortex by use of in vivo microdialysis. Systemic
      administration of idazoxan (0.25 mg/kg, i.p.) produced significant increases in
      extracellular levels of dopamine. The maximum response of the facilitatory effect
      of dopamine release was 241.5%, which was detected 80 min after the injection of
      idazoxan. Idazoxan-induced (0.25 mg/kg, i.p.) increases in dopamine release were
      prevented by an established anxiolytic agent, diazepam (0.5 mg/kg, i.p.) and a
      putative anxiolytic agent tropisetron (100 microg/kg, i.p.). These results
      suggest that the excessive dopaminergic neuronal activity in the rat prefrontal
      cortex is related to idazoxan-induced anxiogenic effects. The idazoxan-induced
      (0.25 mg/kg, i.p.) enhancement of dopamine release was further prevented by
      pretreatment with serotonin (5-hydroxytryptamine; 5-HT) neurotoxin, 5,7
      dihydroxytryptamine (200 microg/kg, i.c.v.). The basal output of dopamine release
      was not altered in 5-HT lesioned rats. These findings indicate that intact
      serotonergic neurons are required for the facilitatory effects of idazoxan on
      dopamine release. In other words, the functional interaction between dopaminergic
      and serotonergic neuronal systems in the rat prefrontal cortex might be involved
      in anxiety or fear.

PMID- 9570465
TI  - Effects of R-84760, a selective kappa-opioid receptor agonist, on nociceptive
      reflex in isolated neonatal rat spinal cord.
AB  - We tested the effects of (3 R)-3-(1-pyrrolidinylmethyl)-4-[(1S)-5,6-dichloro-1
      indancarbony l]-2,3,5,6-tetrahydro-1,4-thiazine hydrochloride (R-84760), a
      selective kappa-opioid receptor agonist, on the slow ventral root potential in
      the isolated spinal cord of neonatal rats. R-84760 at 10 nM decreased the slow
      ventral root potential to 35% of the control, leaving the monosynaptic reflex
      unaffected. The depressant effect of R-84760 progressed slowly for 60 min to the
      maximum and recovered slightly after removal of the drug from the perfusing
      solution. This contrasts with [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO) or
      [MeTyr1, MeArg7, D-Leu-NHEt8]dynorphin A-(1-8) (E-2078) which attained their
      maximum depressant effect within 15 min with recovery immediately after washout.
      Reversibility of the R-84760 effect was observed in vivo in antinociceptive tests
      in mice. R-84760 reduced the depolarization induced by substance P or L-glutamate
      in the normal solution, but not in the presence of tetrodotoxin at 0.3 microM.
      Naloxone inhibited the effect of R-84760 at a higher concentration (1 microM)
      than that (0.1 microM) needed to antagonize the effect of DAMGO. In contrast, R
      84760 was more sensitive to nor-binaltorphimine than was DAMGO. The results show
      that R-84760 selectively inhibits the nociceptive response presynaptically
      through kappa-opioid receptors and that the inhibitory effect is characteristic,
      with long duration, in the neonatal rat spinal cord.

PMID- 9570466
TI  - Effect of the reversible monoamine oxidase-A inhibitor befloxatone on the rat 5
      hydroxytryptamine neurotransmission.
AB  - The aim of the present study was to assess, using in vivo electrophysiological
      paradigms, the effect of sustained administration of the selective and reversible
      monoamine oxidase-A inhibitor beflotaxone on serotonin (5-hydroxytryptamine, 5
      HT) neurotransmission. In male Sprague-Dawley rats with the osmotic minipumps in
      place, a treatment with befloxatone (0.75 mg/kg per day, s.c.) for 2 days
      decreased the spontaneous firing activity of dorsal raphe 5-HT neurons. The
      combination of befloxatone and the 5-HT1A/1B receptor antagonist (-)-pindolol (15
      mg/kg per day, s.c.) for 2 days slightly increased the firing activity of 5-HT
      neurons, whereas a treatment with (-)-pindolol alone for 2 days did not modify
      this parameter. The suppressant effects on the firing activity of 5-HT neurons of
      the 5-HT autoreceptor agonist lysergic acid diethylamide (LSD), injected
      intravenously, and of both 5-HT and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n
      propylamino)-tetralin (8-OH-DPAT), applied by microiontophoresis, were attenuated
      in rats treated with befloxatone for 2 days, suggesting an early desensitization
      of the somatodendritic 5-HT1A receptors. The firing activity of 5-HT neurons was
      back to normal after a treatment for 21 days with befloxatone but the suppressant
      effects of LSD, 5-HT or 8-OH-DPAT was the same as in controls. In contrast, the
      suppressant effect of the alpha2-adrenoceptor agonist clonidine on the firing
      activity of 5-HT neurons was significantly attenuated after the treatment with
      befloxatone for 21 days. At the postsynaptic level, the administration of the
      selective 5-HT1A receptor antagonist (N-[2-[4(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide trihydroxychloride (WAY
      100635, 100 microg/kg, i.v.) did not modify the firing activity of quisqualate
      activated dorsal hippocampus CA3 pyramidal neurons in control rats. In contrast,
      in rats treated with befloxatone in combination with (-)-pindolol for 2 days as
      well as with befloxatone alone for 21 days, WAY 100635 significantly increased
      the firing of CA3 pyramidal neurons. In conclusion, these data suggest that when
      the firing activity of 5-HT neurons is normal in the presence of befloxatone,
      either after a two-day treatment together with (-)-pindolol or alone for 21 days,
      the tonic activation of postsynaptic 5-HT1A receptors is enhanced.

PMID- 9570468
TI  - Cataleptogenic effect of subtype selective 5-HT receptor antagonists in the rat.
AB  - 5-HT receptor antagonists with selectivity for 5-HT1A WAY-100635 (N-[2-[-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide), 5
      HT1B GR 127935 (N-[methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'(5
      methyl-1,2, 4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide x HCl), 5-HT2C SB
      200646A (N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea x HCl) and 5-HT2A (ketanserin,
      fananserin and MDL 100,151 ((+/-)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4
      fluorophenyl)ethyl]-4-pipe ridinemethanol) receptors were tested for
      cataleptogenic responses in rats. WAY-100635 (0.1-3 mg/kg, s.c.), ketanserin (0.1
      3 mg/kg, s.c.), MDL 100,151 (0.3-3 mg/kg, s.c.) and fananserin (RP 62203; 3
      mg/kg, s.c.) induced a significant catalepsy. GR 127935 (1 mg/kg, s.c.), SB
      200646A (without effect per se at 10 mg/kg, s.c.) and MDL 100,151 (0.3 mg/kg,
      s.c.) did not inhibit the cataleptic response to the dopamine D2 receptor
      antagonist, loxapine (0.3 mg/kg, s.c.). Catalepsy induced by MDL 100,151 (3
      mg/kg) was blocked by co-treatment with clozapine, but not by SB 200646A (both at
      10 mg/kg, s.c.). Although clozapine displays significant affinity to 5-HT1A, 5
      HT1B, 5-HT2A and 5-HT2C receptors, the present results suggest that blockade of
      these receptors is not responsible for clozapine's anticataleptic activity.

PMID- 9570467
TI  - Margatoxin increases dopamine release in rat striatum via voltage-gated K+
      channels.
AB  - The distribution of iodinated margatoxin ([125I]margatoxin) binding sites in rat
      was investigated by autoradiography. Rat striatum expresses a high density of
      margatoxin binding sites and, therefore, the effects of margatoxin, charybdotoxin
      and iberiotoxin have been studied on [3H]dopamine release from rat striatal
      slices in vitro. Margatoxin (0.1-100 nM) and charybdotoxin (10-1000 nM), but not
      iberiotoxin increased the spontaneous and the electrically evoked [3H]dopamine
      release. [3H]dopamine release by margatoxin was inhibited by tetrodotoxin and
      omega-conotoxin GVIA, but not by atropine, naloxone, N(omega)-nitro-L-arginine
      and neurokinin or neurotensin receptor antagonists. In the buffer solution used
      for release experiments, [125I]margatoxin labels a maximum of 0.12 pmol of
      sites/mg protein in rat striatal membranes with a Kd of 5 pM. [125I]margatoxin
      binding was inhibited by margatoxin (Ki of 4 pM), charybdotoxin (Ki of 162 pM)
      but not by iberiotoxin. We conclude that inhibition of margatoxin-sensitive
      voltage-gated K+ channels increases [3H]dopamine release demonstrating their role
      in repolarization of nigrostriatal projections. In contrast, iberiotoxin
      sensitive, high-conductance Ca2+-activated K+ channels are not involved in
      release of [3H]dopamine.

PMID- 9570469
TI  - R-(-)-alpha-methyl-histamine has nitric oxide-mediated vasodilator activity in
      the mesenteric vascular bed of the cat.
AB  - Responses to the histamine H3 receptor agonist R-(-)-alpha-methyl-histamine were
      investigated in the mesenteric vascular bed of the cat under constant-flow
      conditions. Injections of R-(-)-alpha-methyl-histamine and histamine caused dose
      related decreases in mesenteric perfusion pressure with R-(-)-alpha-methyl
      histamine being 1000-fold less potent than histamine when doses were compared on
      a nmol basis to take molecular weight into account. Responses to R-(-)-alpha
      methyl-histamine were not altered by histamine H1 or H2 receptor antagonists at a
      time when responses to histamine were significantly reduced. The histamine H3
      receptor antagonist thioperamide reduced responses to R-(-)-alpha-methyl
      histamine but was without effect on responses to histamine [6-[2-(4
      imidazolyl)ethylamino]-N-(4-trifluoro-methylphenyl)heptaneca rdoxamide dimaleate]
      (HTMT), or dimaprit. These data suggest the presence of histamine H1, H2 and H3
      receptors mediating vasodilation in the mesenteric vascular bed. Responses to R-(
      )-alpha-methyl-histamine and histamine were reduced by the nitric oxide synthase
      inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) but were not altered by
      the cyclooxygenase inhibitor meclofenamate, the alpha-adrenoceptor blocker
      phentolamine, or adrenergic nerve terminal depleting agent reserpine. The present
      data suggest that histamine H3 receptors mediating vasodilation are present in
      the mesenteric vascular bed and that responses are mediated by the release of
      nitric oxide but not vasodilator prostaglandins or an effect on the adrenergic
      nervous system. These results indicate that vasodilator responses to histamine
      involve the activation of histamine H1 and H2 receptors and the release of nitric
      oxide in the mesenteric vascular bed of the cat.

PMID- 9570470
TI  - Correction of neurovascular deficits in diabetic rats by beta2-adrenoceptor
      agonist and alpha1-adrenoceptor antagonist treatment: interactions with the
      nitric oxide system.
AB  - The aims were to test whether 2 weeks treatment with the beta2-adrenoceptor
      agonist, salbutamol, or the alpha1-adrenoceptor antagonist, doxazosin, could
      correct nerve blood flow and conduction velocity deficits in 8 week
      streptozotocin-diabetic rats and to examine neurovascular mechanisms using co
      treatment with the nitric oxide synthase inhibitor, NG-nitro-L-arginine. Sciatic
      motor conduction velocity, 20.3% reduced by diabetes, was corrected by 88.2 and
      88.5% for salbutamol and doxazosin, respectively. A 47.6% diabetic deficit in
      sciatic nutritive endoneurial blood, was substantially reversed by salbutamol
      (117.0%) and doxazosin (61.0%) treatment. The effects of alpha1-adrenoceptor
      blockade and beta2-adrenoceptor stimulation on nerve blood flow and conduction
      velocity were almost completely (76.7-91.7%) attenuated by NG-nitro-L-arginine co
      treatment. Thus, the data stress the importance of vasa nervorum alpha1 and beta2
      adrenoceptors and the permissive role of nitric oxide in nerve blood flow control
      mechanisms. They also indicate that beta2-adrenoceptor agonists may be suitable
      for clinical trials of diabetic neuropathy.

PMID- 9570471
TI  - Sulfonylurea effects on acid and pepsinogen secretion in isolated rabbit gastric
      glands.
AB  - The influence of different sulfonylureas on the rate of acid and pepsinogen
      secretion was studied in isolated rabbit gastric glands. Neither tolbutamide (10
      500 microM), chlorpropamide (10-500 microM), glibenclamide (1-50 microM) nor
      glipizide (1-50 microM) exerted a secretory effect. In contrast, gliquidone
      caused a marked and dose-dependent stimulation of acid production in gastric
      glands incubated under basal conditions and potentiated the stimulatory effect of
      both histamine and carbachol. Gliquidone also increased the rate of pepsinogen
      release in gastric glands incubated either under basal conditions or in the
      presence of cholecystokinin-octapeptide or isoproterenol. The secretory effects
      of gliquidone were associated with a significant increase in the glandular
      content of cyclic AMP, caused by a competitive inhibition of low-Km cyclic AMP
      phosphodiesterase. Our results indicate that, among the assayed sulfonylureas,
      only gliquidone, in the micromolar range, stimulates acid and pepsinogen
      secretion through a cyclic AMP-dependent mechanism.

PMID- 9570472
TI  - Inhibitory effect of F-1322 on allergic eosinophil infiltration in airways.
AB  - The effects of F-1322 (N-[2-[4-(benzhydryloxy)piperidino]ethyl]-3-hydroxy-5-(3
      pyridy lmethoxy)-2-naphthamide) on antigen-induced eosinophil infiltration and
      interleukin-5 production in the airways and on in vitro eosinophil migration were
      investigated. F-1322 (10-30 mg/kg, p.o.) inhibited antigen-induced eosinophil
      infiltration and interleukin-5 production in the airways of sensitized mice in a
      dose-dependent manner. Furthermore, F-1322 (0.1-10 microM) prevented the in vitro
      migration of eosinophils from guinea-pigs and humans induced by recombinant human
      interleukin-5, platelet-activating factor, and leukotriene B4 in a concentration
      dependent manner. These results indicate that F-1322 has an inhibitory effect on
      allergic eosinophil infiltration of the airways by preventing both eosinophil
      migration and interleukin-5 production. These pharmacological profiles suggest
      that F-1322 will be a useful therapeutic for allergic diseases, especially
      asthma.

PMID- 9570473
TI  - Effect of oxatomide on T-cell activation and the production of interferon-gamma
      in mite sensitive asthma.
AB  - Interleukin-2 responsiveness of lymphocytes induced by Dermatophagoides farinae
      antigen was suppressed upon exposure to 20 to 2000 ng/ml of oxatomide for 24 h in
      a dose-related manner in children with mite-sensitive bronchial asthma.
      Suppression was greater in the plastic-adherent antigen-presenting cells than in
      the T-cells. Oxatomide suppressed the production of interleukin-1alpha induced by
      Dermatophagoides farinae antigen in plastic-adherent cells. These results
      indicate that the target cells of oxatomide are antigen-presenting cells and not
      T-cells. Oxatomide also suppressed interleukin-2 responsiveness in lymphocytes
      exposed to purified protein derivative, but not in those exposed to concanavalin
      A. Unlike its effect on cell proliferation, oxatomide potentiated the
      Dermatophagoides farinae-induced production of interferon-gamma, which was
      suppressed by stimulation with Dermatophagoides farinae antigen in lymphocytes
      from the patients. In contrast, production of interferon-gamma induced by
      concanavalin A was not affected by this drug. These results indicate that
      oxatomide suppresses interleukin-2 responsiveness of allergen-activated helper T
      cells and increases the production of interferon-gamma induced by
      Dermatophagoides farinae antigen, without causing cell proliferation.

PMID- 9570474
TI  - Mechanism of the inhibitory effect of melatonin on tumor necrosis factor
      production in vivo and in vitro.
AB  - Melatonin is an antioxidant. Since other antioxidants inhibit the production of
      tumor necrosis factor (TNF) induced by lipopolysaccharide, we investigated its
      effect on TNF production in vivo and in vitro and on lethality associated with
      endotoxic shock. Administration of melatonin to mice (5 mg/kg, s.c., 30 min
      before or simultaneously with lipopolysaccharide) inhibited serum TNF levels by
      50-80% and improved survival of mice treated with a lethal dose of
      lipopolysaccharide. By studying other, structurally related, indolamines (N
      acetyl-5-hydroxytryptamine, 5-methoxytryptamine and 5-hydroxytryptamine) we found
      a good correlation between antioxidant activity (for which the 5-methoxy group is
      essential) and the inhibition of TNF production in vivo and in vitro in
      mononuclear cells. Melatonin did not increase serum corticosterone and did not
      modify the elevation of serum corticosterone levels by lipopolysaccharide or by
      interleukin-1. Furthermore, it exerted its inhibitory effect in adrenalectomized
      or hypophysectomized mice also, indicating that its effect is independent of the
      hypothalamus-pituitary-adrenal axis.

PMID- 9570475
TI  - Mast cell degranulation induced by two phospholipase A2 homologues: dissociation
      between enzymatic and biological activities.
AB  - Bothropstoxin-I and bothropstoxin-II are phospholipase A2 homologues isolated
      from Bothrops jararacussu snake venom. The former is devoid of phospholipase A2
      activity whereas the latter has very low enzymatic activity. In this study, we
      have investigated the in vivo (rat paw and skin oedema) and in vitro (mast cell
      degranulation) inflammatory effects caused by bothropstoxin-I and bothropstoxin
      II. Bothropstoxin-I (25-100 microg/paw) and bothropstoxin-II (12.5-50 microg/paw)
      caused dose-dependent rat paw oedema. The intradermal injection of bothropstoxin
      I (0.125-5 microg/site) and bothropstoxin-II (0.125-5 microg/site) into rat skin
      also resulted in dose-dependent oedema formation. These oedematogenic activities
      were largely reduced in animals pretreated with the histamine/5-hydroxytryptamine
      (5-HT) receptor antagonist cyproheptadine (2 mg/kg, i.p. 0.5 h before).
      Similarly, p-bromophenacyl bromide, a compound known to inhibit phospholipase A2
      activity, significantly inhibited rat paw and skin oedema induced by both
      phospholipase A2 homologues. The polyanion heparin (5 IU/site) significantly
      reduced the rat skin oedema induced by either bothropstoxin-I or bothropstoxin-II
      as well as the paw oedema (50 IU/site) induced by the former. When assayed in the
      rat peritoneal mast cells in vitro, both bothropstoxin-I (10 and 100 microg/ml)
      and bothropstoxin-II (3 and 10 microg/ml) significantly caused [14C]5-HT release.
      The [14C]5-HT release caused by these phospholipase A2 homologues were reduced by
      p-bromophenacyl bromide and heparin (50 IU/ml). Our results indicate that oedema
      formation induced by bothropstoxin-I and bothropstoxin-II is mostly dependent on
      in vivo mast cell degranulation. Since heparin greatly reduced the oedematogenic
      activity of these phospholipase A2 homologues, it is likely that the cationic
      charge of these substances plays a major role in the mast cell activation. Our
      results also indicate that p-bromophenacyl bromide may not be a suitable
      pharmacological tool to investigate the correlation between enzymatic activity
      and the inflammatory effects of phospholipases A2.

PMID- 9570476
TI  - Glutamate-stimulated proliferation of rat retinal pigment epithelial cells.
AB  - We investigated the effects of glutamate on cell proliferation and the expression
      of basic fibroblast growth factor (bFGF) and its receptor (FGF-R1) mRNA in
      cultured rat retinal pigment epithelial (RPE) cells. The number of primary RPE
      cells was significantly higher after treatment with 0.2 to 1.0 mM glutamate
      (maximum at 1.0 mM) for 7 days than in controls. Glutamate-stimulated cell
      proliferation was abolished by (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine (MK-801), but not by 6,7-dinitroquinoxaline
      2,3-dione or L(+)-2-amino-3-phosphonopropionic acid. Proliferation was increased
      to a similar extent by N-methyl-D-aspartate (NMDA), but not by kainate, alpha
      amino-3-hydroxy-3-methyl-4-isoxazolepropionic acid or trans-(+/-)-1-amino-1,3
      cyclopentanedicarboxylic acid. NMDA-receptor-like immunoreactivity was detected
      in most cells cultured. Treatment of cells with glutamate increased the level of
      bFGF mRNA and, to a lesser extent, that of FGF-R1 mRNA, which peaked 2 and 4
      days, respectively, after glutamate was added. The increase in bFGF mRNA induced
      by glutamate was inhibited by MK-801. These findings suggest that glutamate might
      stimulate proliferation of RPE cells through activation of NMDA receptors and
      expression of bFGF and further suggest that glutamate may be involved in the
      proliferative changes of RPE cells in retinal wound healing.

PMID- 9570477
TI  - Identification of a unique ligand which has high affinity for all four bombesin
      receptor subtypes.
AB  - Four subtypes of bombesin receptors are identified (gastrin-releasing peptide
      receptor, neuromedin B receptor, the orphan receptor bombesin receptor subtype 3
      (BB3 or BRS-3) and bombesin receptor subtype 4 (BB4)), however, only the
      pharmacology of the gastrin-releasing peptide receptor has been well studied.
      This lack of data is due in part to the absence of a general ligand. Recently we
      have discovered a ligand, 125I-[D-Tyr6,betaAla11,Phe13,Nle14]bombesin-(6-1 4)
      that binds to BRS-3 receptors. In this study we investigate its ability to
      interact with all four bombesin receptor subtypes. In rat pancreatic acini
      containing only gastrin-releasing peptide receptor and in BB4 transfected BALB
      cells, this ligand and 125I-[Tyr4]bombesin, the conventional gastrin-releasing
      peptide receptor ligand, gave similar results for receptor number, affinity for
      bombesin and affinity for the unlabeled ligand. In neuromedin B receptor
      transfected BALB cells, this ligand and 125I-[D-Tyr0]neuromedin B, the generally
      used neuromedin B receptor ligand, gave similar results for receptor number,
      neuromedin B affinity or the unlabeled ligand affinity. Lastly, in BRS-3
      transfected BALB cells, only this ligand had high affinity. For all four bombesin
      receptors this ligand had an affinity of 1-8 nM and was equal or greater in
      affinity than any other specific ligands for any receptor. The unlabeled ligand
      is specific for gastrin-releasing peptide receptors on rat pancreatic acini and
      did not inhibit binding of 125I-cholecystokinin octapeptide (125I-CCK-8), 125I
      vasoactive intestinal peptide (125I-VIP) or 125I-endothelin to their receptors.
      The unlabeled ligand was an agonist only at the gastrin-releasing peptide
      receptor in rat acini and did not interact with CCK(A) receptors or muscarinic M3
      acetylcholine receptors to increase [3H]inositol phosphates. These results
      demonstrate 125I-[D-Tyr6,betaAla11,Phe13,Nle14]bombesin-(6-1 4) is a unique
      ligand with high affinity for all subtypes of bombesin receptors. Because of the
      specificity for bombesin receptors, this ligand will be a valuable addition for
      such pharmacological studies as screening for bombesin receptor agonists or
      antagonists and, in particular, for investigating BRS-3 cell biology, a receptor
      for which no ligand currently exists.

PMID- 9570478
TI  - A novel beta-adrenoceptor ligand for positron emission tomography: evaluation in
      experimental animals.
AB  - Myocardial and pulmonary beta-adrenoceptors can be imaged and quantified with the
      antagonist (S)-4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-b
      enzimidazol-2-[11C]-one (S-[11C]CGP-12177). The synthesis of this ligand (based
      on the reaction of a precursor with [11C]phosgene) is laborious and in many
      centers the final product has a low and variable specific activity. This prevents
      widespread use of S-[11C]CGP-12177 for studies in patients. We prepared S
      [11C]CGP-12388, the isopropyl analogue of CGP-12177, by a reliable one-pot
      procedure and evaluated the radiopharmaceutical for beta-adrenoceptor imaging.
      Blocking experiments with subtype-selective beta-adrenergic drugs showed that
      myocardial and pulmonary uptake of S-[11C]CGP-12388 in anesthetized rats reflects
      ligand binding to beta1- and beta2-adrenoceptors. In this animal model,
      clearance, metabolism and tissue/plasma ratios of S-[11C]CGP-12388 were similar
      to those of S-[11C]CGP-12177. A [18F]fluoroisopropyl analogue of CGP-12177 showed
      less favorable characteristics. S-[11C]CGP-12388 was therefore selected for
      evaluation in humans and it may become the tracer of choice for clinical studies
      since it is easily prepared.

PMID- 9570479
TI  - Angiotensin II stimulation of the stress-activated protein kinases in renal
      mesangial cells is mediated by the angiotensin AT1 receptor subtype.
AB  - Treatment of renal mesangial cells with the vasoconstrictor angiotensin II
      stimulates a concentration-dependent increase in stress-activated protein kinase
      (SAPK) activity as measured by phosphorylation of the substrate c-Jun. Time
      course studies reveal a transient SAPK activation by angiotensin II which is
      maximal after 5-10 min of stimulation and rapidly declines thereafter to basal
      levels within 30 min. Using the highly selective angiotensin II AT1 receptor
      antagonist valsartan, a concentration-dependent inhibition of angiotensin II
      induced SAPK activity is observed, clearly implying the AT1-receptor in this
      angiotensin II-mediated response. To further elucidate the mechanism involved in
      angiotensin II-induced SAPK activation, cells were treated with different
      inhibitors. Genistein, a tyrosine kinase inhibitor, greatly blocks (by 90%) the
      angiotensin II response, whereas pertussis toxin only partially inhibits
      angiotensin II-activated SAPK activity (by 76%). A highly potent protein kinase C
      inhibitor [3-[1-[3-(amidinothio)propyl-1H-indoyl-3-yl]-3-(1-methyl-1H- indoyl-3
      yl) maleimide methane sulfonate], Ro 31-8220, as well as protein kinase C
      depletion from the cells by prolonged phorbol ester pretreatment, fail to inhibit
      the angiotensin II-induced SAPK activation. In summary these results suggest that
      angiotensin II AT1-receptor is able to activate the SAPK cascade in mesangial
      cells by a pathway independent of protein kinase C, but requiring both pertussis
      toxin-sensitive and -insensitive G-proteins and tyrosine kinase activation.

PMID- 9570480
TI  - Characterization of 5-HT1A receptor-mediated [35S]GTPgammaS binding in rat
      hippocampal membranes.
AB  - Stimulation of [35S]GTPgammaS binding by serotonin (5-hydroxytryptamine, 5-HT)
      receptor ligands was characterized in rat hippocampal membranes. The optimized
      assay contained 30-50 microg protein, 300 microM GDP and 0.1 nM [35S]GTPgammaS,
      incubated at 37 degrees C for 20 min. At 10 microM, the 5-HT1A receptor agonist
      R(+)-8-hydroxy-2-(di-n-propylamino)tetralin [R(+)-8-OH-DPAT] stimulated GTPgammaS
      binding from 27.1 +/- 2.5 to 45.7 +/- 4.2 fmol/mg protein. Increasing the protein
      concentration did not affect the absolute difference between basal and maximal
      GTPgammaS binding nor the EC50, but decreased the percent stimulation. The non
      selective agonists serotonin and 5-carboxamidotryptamine were 30-35% more
      efficacious, whereas the partial agonists buspirone and S(-)-8-hydroxy-2-(di-n
      propylamino)tetralin stimulated GTPgammaS binding by 19 +/- 1 and 43 +/- 3%,
      respectively, compared to R(+)-8-OH-DPAT. Neither the 5-HT2 receptor agonist [(+/
      )1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] (DOI) nor the 5-HT1A receptor
      antagonists WAY 100,635 (n-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-n-(2
      pyridinyl) cyclohexanecarboxamide trihydrochloride) and spiperone altered basal
      GTPgammaS binding. WAY 100,635 abolished the effect of R(+)-8-OH-DPAT, but only
      reduced the effect of serotonin by 88 +/- 3%. Finally, methiothepin antagonized
      R(+)-8-OH-DPAT-stimulated GTPgammaS binding and reduced basal GTPgammaS binding
      by itself. The reduction was not affected by WAY 100,635. We have characterized a
      method to assess functional activity at 5-HT1A receptors in rat hippocampal
      membranes by measuring agonist-induced [35S]GTPgammaS binding.

PMID- 9570481
TI  - The ability of verapamil to restore intracellular accumulation of anthracyclines
      in multidrug resistant cells depends on the kinetics of their uptake.
AB  - The basic distinguishing feature of all cells expressing functional P
      glycoprotein-multidrug resistance is a decrease of steady state drug levels as
      compared to those in drug-sensitive controls. A variety of small molecules, such
      as verapamil and cyclosporin A, bind to P-glycoprotein and inhibit its ability to
      pump out antitumor drugs. The kinetics of P-glycoprotein-mediated efflux of
      various anthracycline derivatives was measured in multidrug-resistant (MDR) K562
      cells in the presence of verapamil. Used for the purpose were daunorubicin,
      idarubicin and 8-S-fluoro-idarubicin which have the same pKa of deprotonation
      equal to 8.4, but different lipophilicity, 4'-epi-2'-bromo-daunorubicin which has
      a lipophilicity which is comparable to that of daunorubicin but a pKa equal to
      6.3, pirarubicin with pKa equal to 7.7 and lipophilicity different from that of
      these derivatives were used. Our data show (1) that verapamil is unable to
      completely block the P-glycoprotein-mediated efflux of anthracyclines and that
      10% of its functionality remains even with high verapamil concentrations, (2)
      that the ability of verapamil to restore intracellular accumulation of
      anthracyclines in MDR cells depends on the kinetics of their uptake. With fast
      kinetics uptake, as is the case for idarubicin, 8-S-fluoro-idarubicin, 4'-epi-2'
      bromo-daunorubicin and pirarubicin (which have either a low pKa and/or high
      lipophilicity), verapamil can restore in multidrug resistant cells an
      intracellular drug level which is comparable to that observed in sensitive cells.
      This is not possible when the kinetics of uptake is low as is the case for
      daunorubicin. Cyclosporin A is a more potent modulator and is able to fully
      restore daunorubicin accumulation in multidrug resistant cells.

PMID- 9570482
TI  - N- and C-terminal structure-activity study of angiotensin II on the angiotensin
      AT2 receptor.
AB  - The predominant angiotensin II receptor expressed in the human myometrium is the
      angiotensin AT2 receptor. This preparation was used for a structure-activity
      relationship study on angiotensin II analogues modified in positions 1 and 8. The
      angiotensin AT2 receptor present on human myometrium membranes displayed a high
      affinity (pKd = 9.18) and was relatively abundant (53-253 fmol/mg of protein).
      The pharmacological profile was typical of an angiotensin AT2 receptor with the
      following order of affinities: (angiotensin III > or = angiotensin II >
      angiotensin I > PD123319 > angiotensin-(1-7) > angiotensin-(1-6) approximately
      angiotensin IV >> Losartan). Modifications of the N-terminal side chain and of
      the primary amine of angiotensin II were evaluated. Neutralisation of the
      methylcarboxylate (Asp) to a methylcarboxamide (Asn) or to a hydroxymethyl (Ser)
      or substitution for a methylsulfonate group (cysteic acid) improved the affinity.
      Extension from methylcarboxylate (Asp) to ethylcarboxylate (Glu) did not affect
      the affinity. Introduction of larger side chains such as the bulky p
      benzoylphenylalanine (p-Bpa) or the positively charged Lys did not substantially
      affect the affinity. Complete removal of the side chain (angiotensin III),
      however, resulted in a significant affinity increase. Removal or acetylation of
      the primary amine of angiotensin II did not noticeably influence the affinity.
      Progressive alkylation of the primary amine significantly increased the affinity,
      betain structures being the most potent. It appears that quite important
      differences exist between the angiotensin AT1 and AT2 receptors concerning their
      pharmacological profile towards analogues of angiotensin II modified in position
      1. On position 8 of angiotensin II, a structure-activity relationship on the
      angiotensin AT2 receptor was quite similar to that observed with angiotensin AT1
      receptor. Bulky, hydrophobic aromatic residues displayed affinities similar to or
      even better than [Sarcosine1]angiotensin II. Aliphatic residues, especially those
      of reduced size, caused a significant decrease in affinity especially
      [Sarcosine1, Gly8]angiotensin II who showed a 30-fold decrease. Introduction of a
      positive charge (Lys) at position 8 reduced the affinity even further.
      Stereoisomers in position 8 (L-->D configuration) also induced lower affinities.
      The angiotensin AT2 receptor display a structure-activity relationship similar to
      that observed on the AT1 receptor for the C-terminal position of the peptide
      hormone. Position 1 structure-activity relationships are however fundamentally
      different between the angiotensin AT1 and AT2 receptor.

PMID- 9570483
TI  - Economic comparisons of the pharmacotherapy of depression: an overview.
AB  - As many countries find that their health care expenditure is taking up an
      increasing proportion of their financial resources, economic aspects of care
      processes have become more important in the choice of optimal strategies. This
      review of the economic studies of the comparative treatment of depression shows
      that nearly every aspect of treatment has important economic consequences. Cost
      of-illness studies have documented the high burden on society of this disorder,
      and the associated loss of productivity and work. Comparative cost
      effectiveness/utility studies, the majority of which are based on modelling
      techniques, have consistently shown a better cost-effectiveness ratio of the
      newer antidepressants over more traditional tricyclic antidepressants (TCAs),
      when all therapy-related costs are taken into account.

PMID- 9570484
TI  - Mental health problems among homeless adolescents.
AB  - This paper reviews 18 surveys of mental health problems among homeless
      adolescents and reports on a pilot study of the same topic conducted in
      Amsterdam. Sampling methods and measures of mental health are discussed. The
      reported estimates of mental health problems vary greatly, very probably because
      of methodological differences. Despite the different methods used, there seems to
      be considerable research evidence to support a high prevalence of mental
      disorders among homeless adolescents. The results of the pilot study of 50
      homeless adolescents in Amsterdam are consistent with the surveys reviewed. A
      highly structured interview was conducted at all four services sites for homeless
      adolescents in Amsterdam. Of the homeless adolescents interviewed, 78% had at
      least one lifetime DIS/DSM-III-R diagnosis, and 64% had at least one 1-month
      diagnosis.

PMID- 9570485
TI  - Possible antecedents of DSM-III-R personality disorders.
AB  - In order to extend our knowledge of the effects of environmental influences upon
      personality disorder (PD) pathology, childhood traumatic events and parental
      bonding were studied in 90 PD in-patients of both sexes. Childhood traumatic
      experiences (primarily physical and/or sexual abuse) and parental bonding
      dimensions were correlated with PD pathology depending on PD type and cluster.
      Important differences were found between the sexes. The quality of the paternal
      relationship (high control, low care) was significantly associated with PD
      pathology in men, whereas childhood traumatic experiences and the quality of
      maternal parenting were associated with PD pathology in women. The study of
      traumatic events such as childhood abuse has recently been the focus of
      considerable attention. More emphasis in empirical research needs to be given to
      parental relationships, especially in the case of men.

PMID- 9570487
TI  - Semiology and subtyping of panic disorders.
AB  - To date, the quantitative psychopathology of panic disorder (PD) has been less
      well studied than that of other psychiatric conditions such as schizophrenia or
      major depression. The aim of the present study was to assess the frequency and
      factorial grouping of symptoms in a naturalistic sample of PD patients. A total
      of 274 consecutive cases of PD who contacted an out-patient clinic in Barcelona,
      Spain were assessed by two experienced interviewers. The assessment instruments
      included the Structured Clinical Interview for DSM-III-R Upjohn version (SCID-UP
      R) and an inventory of panic attack symptoms based on DSM-III-R. Of the patients
      who presented at the unit during the assessment period, 8.5% presented with PD.
      Palpitations, shortness of breath, fear of dying and dizziness were the most
      frequent and intense symptoms reported by the PD patients. Principal-component
      analysis revealed four factors which accounted for 57% of the variance, including
      'cardiorespiratory' (26.1%) and 'vestibular' (15.1%) factors, and two additional
      factors with mixed symptoms. The frequency of presentation of symptoms was
      similar to that reported in other studies. However, some discrepancies were
      observed that may be attributed to transcultural differences as well as to
      terminological problems and the range of symptoms assessed. These factors may
      also explain some of the differences found in factor analysis groupings in
      previous studies. Our findings support the symptom subtyping of PD.

PMID- 9570486
TI  - Psychological morbidity and HIV in Kenya.
AB  - This paper describes a cross-sectional study with subjects and raters blind to
      HIV status to assess psychiatric morbidity associated with HIV in a sample of
      working adults in Western Kenya. Subjects were recruited from an occupational
      health clinic for statutory annual health checks of workers in the food industry.
      Psychiatric interviews and neuropsychological tests were conducted. Of 230
      subjects, 34% were HIV positive. Women had a higher rate than men, and those who
      worked as bargirls or were divorced, widowed or separated were particularly at
      risk. There were no substantial differences in psychiatric morbidity or
      neuropsychological functioning between the HIV-positive and HIV-negative
      subjects.

PMID- 9570488
TI  - Expatriate mental health.
AB  - This paper reviews the historical aspects of expatriate mental health, and
      comments on the paucity of literature in the medical and psychiatric journals.
      Data obtained from 397 expatriate probands examined during overseas service are
      described. It was noted that there was a high incidence of affective and
      adjustment disorders. The results showed six areas significantly related to those
      with affective disorders at interview, namely a history of consultation for
      psychological problems in out-patient departments or with the patient's own
      doctor, a history of depressed mood, and a family history of suicide, psychosis
      or personality disorder. Subjects with adjustment disorders at interview showed a
      significant positive correlation with four stressors (occupational anxiety, home
      country anxieties, acculturation and physical ill-health), but showed a negative
      association with a past personal history of consultation for psychological
      problems at out-patient departments or with their own doctors. These findings are
      discussed and practical applications suggested for improving expatriate mental
      health.

PMID- 9570489
TI  - Factors predictive of regret in sex reassignment.
AB  - The objective of this study was to evaluate the features and calculate the
      frequency of sex-reassigned subjects who had applied for reversal to their
      biological sex, and to compare these with non-regretful subjects. An inception
      cohort was retrospectively identified consisting of all subjects with gender
      identity disorder who were approved for sex reassignment in Sweden during the
      period 1972-1992. The period of time that elapsed between the application and
      this evaluation ranged from 4 to 24 years. The total cohort consisted of 218
      subjects. The results showed that 3.8% of the patients who were sex reassigned
      during 1972-1992 regretted the measures taken. The cohort was subdivided
      according to the presence or absence of regret of sex reassignment, and the two
      groups were compared. The results of logistic regression analysis indicated that
      two factors predicted regret of sex reassignment, namely lack of support from the
      patient's family, and the patient belonging to the non-core group of
      transsexuals. In conclusion, the results show that the outcome of sex
      reassignment has improved over the years. However, the identified risk factors
      indicate the need for substantial efforts to support the families and close
      friends of candidates for sex reassignment.

PMID- 9570490
TI  - Quality of life in schizophrenia and dysthymia.
AB  - Quality of life (QOL) was assessed in three groups of patients, consisting of 30
      schizophrenic patients with duration of illness <2 years, 30 schizophrenic
      patients with duration of illness > or = 2 years and 30 dysthymic patients. The
      diagnoses were made according to ICD-10. Two scales of quality of life were used,
      one of which was specific for schizophrenia, while the other was generic for all
      patients. On inter-group comparison the two schizophrenia groups did not show
      significant differences in quality of life, but on comparing schizophrenic and
      dysthymic patients, significant differences emerged. Dysthymic patients were
      significantly less satisfied than schizophrenic patients with duration of illness
      <2 years in the domain of physical health. In the domains of satisfaction with
      medication and leisure-time activities, both schizophrenic groups were
      significantly more satisfied than the dysthymic group. Comparison of the quality
      of life ratings of our patients with those of a well-known study from Sweden
      revealed some significant differences which relate to the domains of work,
      contacts, inner experience and leisure-time activities. Cultural factors are
      invoked to account for these differences. The need for refinement of assessment
      of quality of life in multi-racial and multi-ethnic contexts is stressed.

PMID- 9570491
TI  - Neurocognitive function and insight in schizophrenia: support for an association
      with impairments in executive function but not with impairments in global
      function.
AB  - It remains unclear how impaired insight and neurocognitive impairment are related
      to one another in schizophrenia. In order to examine this relationship, subjects
      with schizophrenia or schizoaffective disorder were classified as having
      'impaired' (n=38) or 'unimpaired' (n=43) insight based on their insight rating on
      the Positive and Negative Syndrome Scale (PANSS). Their performance on
      neuropsychological tests of global function, executive function, memory and
      vigilance was then compared. Multivariate analyses followed by Scheffe tests
      indicated that subjects with impaired insight performed less well on the
      Wisconsin Card Sorting Test, demonstrating poorer abstract flexibility and
      heightened perseveration. No differences were found between the groups with
      regard to global cognitive function, memory or vigilance. This suggests that
      insight is closely linked to deficits in executive function, and that it may be
      associated with the compromise of frontal lobe function.

PMID- 9570493
TI  - Blood levels of cytokines in elderly patients with major depressive disorder.
AB  - Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and
      tumour necrosis factor alpha (TNFalpha) were measured in 10 elderly women with
      major depressive disorder (MDD) and in two groups of controls, one consisting of
      10 age-matched healthy female volunteers and one consisting of 10 young healthy
      female volunteers. The cytokine concentrations were measured in MDD patients
      before and after 30 days of treatment with phosphatidylserine (BC-PS), 600 mg
      daily p.o. The plasma IL-Ibeta, IL-6 and TNFalpha concentrations did not differ
      significantly in young controls, elderly controls and MDD patients. BC-PS
      therapy, while significantly improving the depressive symptoms, did not alter the
      cytokine concentrations.

PMID- 9570492
TI  - Serum levels of excitatory amino acids, serine, glycine, histidine, threonine,
      taurine, alanine and arginine in treatment-resistant depression: modulation by
      treatment with antidepressants and prediction of clinical responsivity.
AB  - Previous research has revealed that major depression is accompanied by disorders
      in excitatory amino acids, e.g. glutamate and aspartate, and alterations in serum
      levels of other amino acids, e.g. serine, glycine and taurine. The aim of the
      present study was to examine serum levels of aspartate, asparagine, glutamate,
      glutamine, serine, glycine, threonine, histidine, alanine, taurine and arginine
      in major depression patients with treatment-resistant depression (TRD). No
      significant differences in the serum concentrations of any of the above amino
      acids could be found between patients with and without TRD and normal controls.
      Non-responders to treatment with antidepressants during a period of 5 weeks were
      characterized by significantly lower serum levels of aspartate, asparagine,
      serine, threonine and taurine. A 5-week period of treatment with antidepressants
      significantly reduced the serum levels of aspartate, glutamate and taurine, and
      significantly increased the serum concentrations of glutamine. The results
      suggest that alterations in serum levels of aspartate, asparagine, serine,
      threonine and taurine may predict the subsequent response to treatment with
      antidepressants, and that the latter may modulate serum levels of excitatory
      amino acids and taurine.

PMID- 9570494
TI  - Influence of different transplantation methods on liver cell survival in spleens
      of rats.
AB  - Isolated hepatocytes, liver tissue suspensions, or liver tissue cylinders from
      biopsies were transplanted into the spleens of adult male rats. Donors were
      syngenic fetuses, syngenic or allogenic adult rats, or autologous material was
      obtained from the rat's own liver. The outcome of the different transplantation
      procedures was evaluated at 1 and 6 months after surgery. Additionally the
      influence of a 30% hepatectomy (HX) on the result of the transplantation was
      investigated. When fetal material was transplanted, the best results in sequence
      with respect to the number of viable hepatocytes within the spleens were obtained
      (1) after transplantation of syngenic fetal liver tissue suspensions, (2)
      syngenic fetal liver tissue cylinders and (3) syngenic fetal isolated
      hepatocytes. HX only improved the results with transplantation of syngenic fetal
      isolated hepatocytes. After transplantation of syngenic fetal liver tissue
      suspensions and isolated hepatocytes, but not after transplantation of syngenic
      fetal liver tissue cylinders, the number of hepatocytes was higher at 6 months
      than at 1 month after surgery. Concerning syngenic adult liver material, only
      transplantation of isolated hepatocytes lead to a remarkable and increasing
      number of surviving hepatocytes at both 1 and 6 months after surgery. These
      results were further improved by HX. With syngenic adult liver, the other
      transplantation methods yielded no or nearly no viable hepatocytes in the
      spleens. In comparison to the results after transplantation of syngenic fetal
      liver tissue suspensions, transplantation of syngenic adult isolated hepatocytes
      was less efficient, but still yielded more viable hepatocytes than the
      transplantation of syngenic fetal isolated hepatocytes. After transplantation of
      autologous liver tissue suspensions, autologous liver tissue cylinders or
      allogenic adult liver material only few surviving hepatocytes were observed. At 1
      month after transplantation of syngenic fetal liver material, syngenic adult
      isolated hepatocytes or autologous liver tissue cylinders into the spleens 40-80%
      of the explants consisted of bile ducts independent from the transplantation
      method. At 6 months after surgery the bile ducts were much less and in some cases
      no longer visible. After transplantation of autologous liver tissue suspensions
      or allogenic adult liver material only very few bile ducts were seen, but anyhow
      in those cases only poor results were obtained. Thus, with respect to
      transplantation outcome and long-term liver cell survival, intrasplenic
      transplantation of both syngenic fetal liver tissue suspensions and syngenic
      adult isolated hepatocytes seem to be the most suitable methods and should be
      chosen for further investigations on explant morphology and function.

PMID- 9570495
TI  - Possible role of endogenous prostacyclin in the maintenance of hepatic integrity
      in rat.
AB  - Exogenously administered prostaglandins are reported to be involved in hepatic
      regeneration, i.e. they hinder liver cell injury and cell-death induced by
      different toxic noxae. In the pertinent literature no data are available
      regarding the role of endogenous (tissue) prostaglandins in hepatotoxic
      processes. In subchronic carbon-tetrachloride intoxication (800 mg/kg twice a
      week, s.c., for 12 weeks) the endogenous prostacyclin level showed a transient
      and significant elevation signalling (similarly to the gastrointestinal tract)
      the process of protective mechanisms. This tenet was further strengthened by the
      concomitant decrease of serum ALT and AST levels. Continuing the carbon
      tetrachloride treatment, finally not only the endogenous prostacyclin
      synthesising capacity of the liver but the hepatic cells themselves were also
      destroyed. According to the author's best knowledge these are the first data in
      the literature which try to enlighten the protective role of endogenous
      prostacyclin in hepatotoxic processes.

PMID- 9570496
TI  - Immunohistochemical measurement of cell proliferation as replicative DNA
      synthesis in the liver of male Fischer 344 rats following a single exposure to
      nongenotoxic hepatocarcinogens and noncarcinogens.
AB  - We aimed to modify an in vivo/in vitro hepatocyte replicative DNA synthesis (RDS)
      test using autoradiography of [3H]methylthymidine (3HTdR) into a nonradioactive
      in vivo version by applying 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry.
      The effects of 12 nongenotoxic hepatocarcinogens and 4 noncarcinogens on RDS
      induction and histological changes in the liver of male Fischer 344 (F344) rats
      were investigated 24 or 48 hrs after a single oral administration at diverse dose
      levels. A statistically significant, dose-related elevation in BrdU labeling
      indices (LI) was obtained for all of the 12 nongenotoxic hepatocarcinogens with
      only one exception of D,L-ethionine at relatively lower dose levels. No increase
      was observed in LI for any of the four noncarcinogens examined. From the results
      of histopathological evaluation, the increase in hepatocyte proliferation by
      carbon tetrachloride (CCl4), chloroform (CHCl3), and thioacetamide (TAA) was
      confirmed to be a regenerative liver response following cytotoxicity. Conversely,
      safrole, tannic acid, and urethane yet hepatotoxicants did not show inflammatory
      reaction or necrosis under the condition of the present study, and hence their
      mode of action by which they induce proliferative response was not obvious. The
      results of this study showed that the in vivo version of RDS test efficiently
      discriminated nongenotoxic hepatocarcinogens from noncarcinogens, while it did
      not well clarify the induction mode of cell proliferation.

PMID- 9570497
TI  - Platelet-activating factor receptor-antagonist (BN 52021) stabilizes the
      oxidative-antioxidative balance and attenuates the morphological changes in the
      gastrointestinal tract in experimental hemorrhagic shock.
AB  - The influence of the platelet-activating factor receptor-antagonist (BN 52021)
      and polyelectrolyte solution (PES) on the morphology and oxidant-antioxidant
      equilibrium in the gastrointestinal wall in hemorrhagic shock was examined in
      rats. The animals were divided into five groups: I - control, II - sham
      operation, III - untreated hemorrhagic shock lasting 75 minutes, IV - shock
      treated with PES, and V - shock treated with BN 52021 and PES. The most expressed
      morphological changes were found in the small intestine in group IV (shock
      treated with PES) and in group III (untreated shock). Morphological changes were
      well correlated with the malondialdehyde (MDA) level reflecting oxidative tissue
      injury and with the antioxidative potential: sulfhydryl compounds (-SH) level,
      and superoxide dismutase (SOD) activity. The signs of morphological and
      biochemical injury to the gastrointestinal tract in animals from group V (treated
      with BN 52021 and PES) were significantly less expressed than those in groups III
      and IV. The results suggest an essential role of PAF in oxygen radicals-mediated
      gastrointestinal injury and a beneficial effect of the early application of BN
      52021 in hemorrhagic shock.

PMID- 9570498
TI  - The influence of ethanol and the calcium channel antagonist, nifedipine on
      myocardial ultrastructure in the rat.
AB  - In this study we investigated the ultrastructural changes in rat myocardium
      induced by the concomitant treatment of animals with ethanol and the calcium
      channel antagonist, nifedipine. The animals were given perorally either placebo
      or 8 g/kg body weight ethanol in combination with 3 mg/kg nifedipine for 30 days.
      In contrast to known effects of ethanol on myocardial ultrastructure, the animals
      treated with ethanol and nifedipine did not have cardiomyocyte damage. The most
      common ultrastructural alteration was increased numbers of mitochondria. In a
      previous paper we reported that another calcium channel antagonist, verapamil,
      worsened the toxic effects of ethanol on rat myocardium. Therefore, our data
      could be potentially significant in the selection of a calcium antagonist for
      patients with increased alcohol consumption.

PMID- 9570499
TI  - Influence of hypoxia and hyperthermia upon peroxidative and glutathione status in
      growth-restricted newborn piglets.
AB  - Normal weight (NW) and spontaneously intra-uterine growth-restricted newborn
      piglets (IUGR) were submitted to 1 hour hypoxia and hyperthermia followed by 3
      hours reoxygenation. Glutathione (GSH, GSSG), lipid peroxidation products (TBAR)
      and cytochrome P450 dependent production of reactive oxygen species were studied
      by determination of H2O2 production and amplified chemiluminescence (CL) in brain
      and peripheral organs of NW and IUGR. A severe decrease of GSH was accompanied by
      enhanced H2O2 formation and lipid peroxidation in the brain of both NW and IUGR
      after hypoxia/hyperthermia and reoxygenation. In the other organs studied, only
      muscles showed enhanced lucigenine amplified CL and TBAR production. Nearly the
      same results in NW and IUGR reveal no higher risk of IUGR.

PMID- 9570500
TI  - Gastric chief and parietal cell atrophy induced by a new synthetic retinoid in
      rats and dogs.

PMID- 9570501
TI  - Developmental expression of cytochrome P450 isoforms after transplantation of
      fetal liver tissue suspension into the spleens of adult syngenic rats.
AB  - In the present study, the developmental expression of three cytochrome P450
      (P450) isoforms, 1A1, 2B1 and 3A2, and the ability to store glycogen was
      investigated in intrasplenic liver cell explants in comparison to adult and fetal
      liver. Fetal liver tissue suspensions were transplanted into the spleens of adult
      male syngenic Fisher inbred rats. Animals were sacrificed at 3 days, 1, 2, 4
      weeks, 2, 4, 6 months and 1 year after transplantation. Spleens and livers of
      transplant recipients were compared to those of sham operated and control rats.
      Three days after transplantation little bulks of hepatocytes and only few bile
      ducts were seen in the red pulp of the transplant containing spleens. A massive
      hypertrophy and proliferation of bile ducts and also an augmentation in the
      number of hepatocytes were observed 4 weeks after transplantation. One month
      later, however, the bile ducts had become more and more atrophic, while instead
      the number of hepatocytes continuously increased. One year after surgery large
      masses of hepatocytes with apparent cord structure and only few but well
      preserved bile ducts were seen. Within the livers of adult rats, P450 1A1 was
      only slightly expressed by some hepatocytes around the central veins. P450 2B1
      and 3A2 isoforms expression was much stronger, but also predominantly located in
      the hepatocytes of the central zone of the liver lobule. Hepatocytes of fetal
      livers displayed a moderate P450 1A1 expression. In some cells also a very mild
      staining for P450 2B1 and 3A2 was observed. Within the hepatocytes of the
      intrasplenic liver cell explants P450 1A1 was still expressed 3 days after
      transplantation, disappeared at 1 week after surgery, but reappeared at 4 weeks
      after transplantation. After 2, 4 and 6 months no staining for P450 1A1 was
      detectable any more. One year after transplantation again a slight P450 1A1
      expression appeared. With P450 2B1 and 3A2 a mild to moderate expression was seen
      already at 3 days after transplantation. Four weeks after surgery nearly all of
      the hepatocytes were stained for P450 2B1 and 3A2, but there were marked
      differences between the individual cells in the extent of the expression of these
      two P450 subtypes, like it was also the case with normal adult liver. Within
      hepatocytes of the fetal livers strongly stained glycogen granules were seen,
      which, in comparison to adult livers, were rather coarse-grained. Three days
      after transplantation the glycogen granules in the transplanted hepatocytes were
      still coarse-grained, but from 1 week after transplantation on, they became more
      and more fine-grained. As it was also the case with normal adult liver cells,
      there were marked differences between the individual transplanted hepatocytes in
      their glycogen content. These results demonstrate that transplanted liver cells
      originating from syngenic fetal liver tissue suspensions can survive in host
      organs like the spleen for at least 1 year. They proliferate, differentiate, are
      able to store glycogen, and express different P450 isoforms, like normal adult
      liver cells.

PMID- 9570502
TI  - Functional activity of human hepatocytes under traumatic disease.
AB  - Absorption and fluorescent cytophotometry techniques were applied to studies of
      RNA as well as of total glycogen and its fractions as the parameters of
      functional activity of the hepatocytes in patients with severe mechanical trauma,
      both with and without autointoxication (AI). Slides were stained with
      gallocyanine-chromalums to determine the RNA content and were processed by the
      fluorescent PAS-reaction for the glycogen content. To trace the dynamics of RNA
      and glycogen contents in the liver punction biopsies were done in the same
      patients. A quick increase in the RNA content took place in both groups of
      patients at the first period (within the first 3 days) of traumatic disease. At
      the second period of disease the hepatocyte RNA content in patients without AI
      was found to decrease up to the initial level whereas that in patients with AI
      increased on the average by 36% of the initial values. The total glycogen content
      in hepatocytes of all the patients changed insignificantly in the course of
      disease but its labile fraction in patients with AI decreased to 70% of the
      total. The increase of hepatocyte synthetic activity and the maintenance of the
      high glycogen level are indicative of the large compensatory potential of the
      liver that enables it to carry an intensive functional load under AI conditions.

PMID- 9570503
TI  - Body weight distribution and organ size in newborn swine (sus scrofa domestica) -
      a study describing an animal model for asymmetrical intrauterine growth
      retardation.
AB  - Normal growth is the expression of the genetic potential to growth which is
      neither abnormally constrained nor promoted by internal or external factors.
      Restricted fetal growth is common in human pregnancy and is associated with
      increased perinatal morbidity and mortality. Because of ethical restrictions,
      pathogenetical studies are necessarily dependent on appropriate animal models. In
      the studies presented, evidence will be provided that the naturally occurring
      distribution of body weight in newborn piglets, obtained from n = 512 newborn
      piglets (about 12 hours old) in 50 consecutive deliveries in the breed cohort of
      the mixed German domestic breed - "Deutsches Land-/Edelschwein" gives an
      appropriate sampling for providing a statistically reliable basis with which to
      determine different degrees of fetal growth for further pathophysiological
      studies intended. A strong inverse correlation (r = -0.66, p < 0.05) was found
      between the mean weight of the litter and the number of piglets per litter, and
      an inverse correlation (r = -0.64, p < 0.05) was found between the lowest weight
      of the littermate and the number of piglets per litter. Moreover, gravimetric
      investigations were made into an additional 53 one-day-old newborn piglets
      reflecting the naturally occurring birth weight distribution determined. A marked
      linear correlation between body weights and various organ weights was found
      (values of the correlation coefficient amounted to between 0.45 and 0.98; p <
      0.05). The lowest variation of organ weights was found in the CNS structures
      (0.68-1.33). Skeleton and heart exhibited similar ranges of weight variation
      (0.35-1.81 and 0.38-2.00 of the means) to body weight (0.38-1.77 of the means).
      This was also expressed in the regression analysis, because the slope values were
      0.99 and 0.97 respectively. The hormonal glands investigated, the kidneys, and
      the abdominal parenchymal organs exhibited the largest ranges of weight
      variation. Moreover, regression analysis gives evidence that the weight
      restriction was more pronounced than expected concerning respective body weight.
      This is indicated by slope values > 1 in almost all of those organs. Plasma
      concentration of IGF-1 showed an inverse correlation with body weight (r = -0.42;
      p < 0.05, fig 4). IGF-1 concentration of intrauterine growth retarded (IUGR)
      newborn piglets was in the mean nearly double that of normal weight animals (p <
      0.05) and the brain weight to liver weight ratio was increased more than 2.5
      times in IUGR newborn (fig 5 A, p < 0.05). This investigation provides
      information on the naturally occurring body weight distribution of one-day-old
      piglets, which was obviously a result of epigenetic factors. Gravimetrical
      estimation showed clearly that body weight variety is most probably caused by
      alterations of placental functioning. Severe alterations resulted in asymmetrical
      growth retardation, which was proved by a significantly increased brain to liver
      ratio in animals with a body weight < 10th centile. Thus, evidence is provided
      that naturally occurring asymmetrical intrauterine growth restricted newborn
      piglets can be identified simply by body weight measurement, so that convenient
      conditions are given for pathogenetically motivated studies on intrauterine
      compromised newborns.

PMID- 9570504
TI  - Household insecticides: evaluation and assessment of inhalation toxicity: a
      workshop summary.
AB  - Particularly in tropical countries household insecticides are used on a day-by
      day basis to control mosquitoes, other crawling and flying insects to prevent the
      spread of vector-borne diseases. The products used most often are spray-cans, oil
      sprays, mosquito coils as well as slow-release vaporising systems such as mats
      and liquid vaporiser. The extent and duration of exposure of humans is highly
      dependent on the type of product used. The objective of this workshop was to
      analyse the necessity and feasibility of inhalation studies with household
      insecticides taking into account the specific constrains associated with each
      type of end-use product. The standardisation of inhalation studies with regard to
      the generation of test atmospheres, mode and duration of exposure, and selection
      of adequate toxicological endpoints were addressed. Due to the complex nature of
      exposure atmospheres generated by some household insecticides, viz. mosquito
      coils, it is scientifically challenging to characterise the pathomechanism of
      most concern, since irritant combustion gases, volatile and semi-volatile organic
      substances, particulates (soot), condensation aerosols and re-condensed
      substances onto particulates may act independently, synergistically or mixture
      specific. It has been concluded that for the comparative safety evaluation and
      risk assessment of indoor insecticide end-use products generally recognised
      guidance for harmonised inhalation testing is required: 1) For high-dose release
      products, such as spray-cans, acute inhalation testing appears to be most
      relevant. 2) For low-dose, slow-release devices, subchronic inhalation studies of
      13-weeks, duration of exposure 6 hours/day for 5 consecutive days per week,
      should be performed on rats preferably with the end-use product. A dose-range
      finding study of 2-weeks duration, daily exposure, should be available for the
      justification of dose selection and to demonstrate that the findings of 5
      days/week exposure is not different from that utilising a daily exposure. 3) In
      certain instances, inhalation testing of shorter duration, for example 2 or 4
      weeks, may be appropriate if the inhalation toxicity of the basic formula has
      already been characterised or the major constituents contained in the formulation
      have been examined in extant studies. The duration of study should also depend on
      actual use and exposure pattern, the accumulation potential and the mode of
      action of the ingredients of concern. 4) Particularly for mosquito coil smokes,
      the possible physico-chemical interactions of particulates, potentially irritant
      water soluble or nonsoluble vapours and aerosol or vapours of the active
      ingredient(s) are virtually impossible to predict without appropriate inhalation
      testing. 5) Physiological measurements may be useful for the detection and
      quantification of the respiratory tract sensory irritation potency. Biochemical
      endpoints in lung lavage and conventional histopathology of the lungs and
      extrathoracic airways are considered to be important. 6) It has been agreed that
      the nose-only exposure technique provides the most cost-effective and controlled
      means to expose small laboratory animals to well defined atmospheres as long as
      the limitations of this technique are taken into account.

PMID- 9570505
TI  - Experimental studies on the stem cell concept of liver regeneration. I.
AB  - There are increasing references for the existence of a hepatic stem or progenitor
      cell system as well as its participation in the physiological as well as
      reparative regeneration of the liver and in carcinogenesis. For the physiological
      regeneration the existence of a dynamic "cell-renewal" system finds increasing
      consideration and in the "streaming liver concept" (Zajicek et al. 1985) its
      functional expression. This concept is still under discussion. The present paper
      tries to check this animal-experimentally (Wistar rats) under use of two
      different thymidine analogues (3H-thymidine and Bromodeoxyuridine). In different
      time intervals after labelling (1 h, 14, 30, 60, 90, 120 d) a shift of the
      labelling bias or a migration of the hepatocytes in the liver acinus (Rapaport)
      in portovenous direction could be shown. The average migration speed is 0.575
      microm or 0.0315 cell positions per day, the cell production rate is one in 31.5
      days. The present paper results support the inclusion of a stem or progenitor
      cell system into the physiological regeneration of the liver and allow the
      classification into the "streaming liver concept" (Zajicek et al. 1985).

PMID- 9570506
TI  - Tissue transglutaminase is not increased during apoptosis of HT-1080 human
      fibrosarcoma cells.
AB  - Tissue transglutaminase (tTGase), a cytosolic enzyme which catalyzes the covalent
      cross-linking of proteins, is thought to be involved in the apoptosis. Here, we
      tested whether tTGase is involved during HT-1080 fibrosarcoma cell apoptosis
      induced by the YIGSR (Tyr-Ile-Gly-Ser-Arg) peptide. This sequence is derived from
      the laminin alpha1 chain, and its potency is increased by the formation of a
      16mer polymerization using a lysine tree structure. Cells were treated with
      several different concentrations of Ac-Y 16 for 16 hours, and apoptosis was
      increased in dose-dependent manner. When assayed by incorporation of [14C]
      putrescine into succinylated casein, total transglutaminase activity was
      decreased in parallel with the change in the number of attached cells. Western
      blot analysis using polyclonal antibody against tTGase showed that the tTGase
      protein level had not been significantly changed when equal amounts of the
      protein were applied. To confirm this result, we induced apoptosis of these cells
      by coating the tissue culture plates with non-adhesive poly-hydroxyethyl
      methacrylate (HEMA). Western blot analysis showed that the tTGase protein level
      did not change during this process of apoptosis. Although it has been suggested
      that tTGase is involved in the process of apoptosis of various cells in vitro and
      in vivo, our data demonstrate that tTGase is not involved in the process of
      apoptosis of HT-1080 human fibrosarcoma cell induced by either Ac-Y 16 or a non
      adhesive culture surface.

PMID- 9570507
TI  - The level of MAP kinase activity in the stomach stump in rats after subtotal
      gastrectomy.
AB  - MAPK (Mitogen-Activated Protein Kinase) is one of the elements of kinase cascades
      (MAPK, MEK-MAP kinase, kinase, Raf-1, Ras) regulating cellular proliferation and
      differentiation processes. It seems that the changes in its number and activity
      may be the factor having influence on carcinogenesis. In some human carcinomas a
      significant increase of its activity is observed, in others a decrease of its
      activity is described. Our research aimed at the evaluation of the dynamics of
      precancerous and cancerous changes in the stomach stump in rats after the
      experimental, partial stomach resection. Apart from histological and
      ultrastructural examination we also determined the activity of the sub-unit p42
      MAP kinase. The material comprised segments of gastric mucosa of the stomach
      stump of 15 rats after subtotal gastrectomy. Part of the rats after the procedure
      were administered carcinogen orally (MNNG). On the histological and
      ultrastructural examination we used routine methods, the activity of MAP kinase
      was determined by western-blotting method with the use of IgG against MAPK p42,
      Santa Cruz #154). In 8 examined rats we observed the increase of MAP kinase
      activity. We established probable correlation (without statistical analysis,
      regarding miserly material) between the increase of MAPK activity and
      histological and ultrastructural changes. Among three cases diagnosed as adenoma
      tubulare in two we observed the increase of MAPK activity. A clear increase of
      this kinase was also present in the stomach stump of a rat, which was diagnosed
      as adenocarcinoma. On the basis of our research carried so far we think that the
      increase of the MAPK activity may be one of the causes of the neoplasm
      development. It seems important to obtain the confirmation of our results and to
      establish a possible usefulness of MAPK activity determination as a prognostic
      indicator in case of the neoplasm of stomach stump.

PMID- 9570508
TI  - Activation-inactivation of HIV-1 in the lung.
AB  - The lung is prominently afflicted during the course of HIV-1 disease by both
      infectious and noninfectious complications. Direct or indirect effects of HIV-1
      are likely central to the pathogenesis of these complications. Thus, any changes
      in viral load locally would negatively impact on the lung. This review focuses on
      the endogenous influences (immune effector cells, surfactant) and the exogenous
      factors (including infections such as tuberculosis and noninfectious exposures
      like cigarette smoke) that may contribute to activation or inactivation of HIV-1
      in the lung.

PMID- 9570509
TI  - Regulation of equine infectious anemia virus expression.
AB  - Equine infectious anemia virus (EIAV) is an ungulate lentivirus that is related
      to human immunodeficiency virus (HIV). Much of the understanding of lentiviral
      gene regulation comes from studies using HIV. HIV studies have provided insights
      into molecular regulation of EIAV expression; however, much of the regulation of
      EIAV expression stands in stark contrast to that of HIV. This review provides an
      overview of the current state of knowledge of EIAV regulation by comparing and
      contrasting EIAV gene regulation to HIV. The role of EIAV gene regulation is
      discussed in relation to EIAV pathogenesis.

PMID- 9570510
TI  - Tat, Tat-associated kinase, and transcription.
AB  - The HIV-1 Tat protein is an RNA-binding transcriptional transactivator. Recent
      findings suggest that Tat associates with a cellular kinase that phosphorylates
      the carboxyl-terminal domain of the largest subunit of RNA polymerase II. Here we
      review, in brief, the role of Tat-associated kinase in Tat-activated
      transcription. We discuss evidence that suggests involvement of TFIIH and/or P
      TEFb.

PMID- 9570511
TI  - Recent advances in genetic research on schizophrenia.
AB  - Evidence for genetic factors in schizophrenia is reviewed with regard to family,
      twin and adoption studies, and recent advances in molecular genetic technology
      are applied to explore possible gene loci susceptible to schizophrenia.
      Application of neuropsychological and neuroimaging methodologies are also
      reviewed with an aim to develop criteria for defining phenotypes for genetic
      studies.

PMID- 9570512
TI  - Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in
      basal transcription and nuclear factor recruitment in human glial cells and
      lymphocytes.
AB  - The generation of genomic diversity during the course of infection has the
      potential to affect all aspects of HIV-1 replication, including expression of the
      proviral genome. To gain a better understanding of the impact of long terminal
      repeat (LTR) sequence diversity on LTR-directed gene expression in cells of the
      central nervous system (CNS) and immune system, we amplified and cloned LTRs from
      proviral DNA in HIV-1-infected peripheral blood. Sequence analysis of nineteen
      LTRs cloned from 2 adult and 3 pediatric patients revealed an average of 33
      nucleotide changes (with respect to the sequence of the LAI LTR) within the 455
      bp U3 region. Transient expression analyses in cells of neuroglial and
      lymphocytic origin demonstrated that some of these LTRs had activities which
      varied significantly from the LAI LTR in U-373 MG cells (an astrocytoma cell
      line) as well as in Jurkat cells (a CD4-positive lymphocyte cell line). While
      LTRs which demonstrated the highest activities in U-373 MG cells also yielded
      high activities in Jurkat cells, the LTRs were generally more active in Jurkat
      cells when compared to the LAI LTR. Differences in LTR sequence also resulted in
      differences in transcription factor recruitment to cis-acting sites within the U3
      region of the LTR, as demonstrated by electrophoretic mobility shift assays. In
      particular, naturally occurring sequence variation impacted transcription factor
      binding to an activating transcription factor/cAMP response element binding
      (ATF/CREB) binding site (located between the LEF-1 and distal NF-kappaB
      transcription factor binding sites) that we identified in previous studies of the
      HIV-1 LTR. These findings suggest that LTR sequence changes can significantly
      affect basal LTR function and transcription factor recruitment, which may, in
      turn, alter the course of viral replication in cells of CNS and immune system
      origin.

PMID- 9570514
TI  - Muscular dystrophy: centronucleation may reflect a compensatory activation of
      defective myonuclei.
AB  - Muscular dystrophy has long been believed to be characterized by degeneration and
      abortive regeneration of muscle fibers (the muscle degeneration theory), but
      unfortunately its pathogenesis is still unclear and an effective treatment has
      yet to be developed. As a challenge to the theory, we have proposed an
      alternative muscle-defective-growth theory and a further bone muscle growth
      imbalance hypothesis supposing possible defects in bone-growth-dependent muscle
      growth based on our findings in hereditary dystrophic dy mice (C57BL/6J dy/dy).
      This review presents some new insights into the pathogenesis of the disease along
      with our hypothesis, focusing on the physiological meaning of centronucleation,
      one of the major pathological changes commonly observed in dystrophic muscles of
      man and experimental animals.

PMID- 9570513
TI  - The role of glutamate in the locus coeruleus during opioid withdrawal and effects
      of H-7, a protein kinase inhibitor, on the action of glutamate in rats.
AB  - To investigate the role of glutamate in the locus coeruleus (LC) during opioid
      withdrawal, rats were continuously infused with morphine (a mu-opioid receptor
      agonist, 26 nmol/microl/h) or butorphanol (a mu/delta/kappa-mixed opioid receptor
      agonist, 26 nmol/microl/h) intracerebroventricularly (i.c.v.) via osmotic
      minipumps for 3 days. A direct LC injection of glutamate (1 or 10 nmol/5 microl)
      or naloxone (an opioid receptor antagonist, 24 nmol/5 microl) induced withdrawal
      signs in morphine- or butorphanol-dependent animals. However, these agents failed
      to precipitate any withdrawal signs in saline-treated control animals. On the
      other hand, the expression of withdrawal signs precipitated by the administration
      of glutamate or naloxone in opioid-dependent animals was completely blocked by
      concomitant infusion with 1 or 10 nmol/microl/h of an inhibitor of adenosine
      3',5'-cyclic monophosphate (cAMP)-dependent protein kinase and protein kinase C,
      H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine]. In animals that had been
      infused with opioids in the same manner, i.c.v. injection of naloxone (48 nmol/5
      microl) precipitated withdrawal signs and increased extracellular fluid levels of
      glutamate in the LC of morphine- or butorphanol-dependent rats measured by in
      vivo microdialysis method. However, concomitant infusion with H-7 inhibited the
      increases of glutamate levels in the LC. These results strongly suggest that an
      expeditious release of glutamate in the LC region plays an important role in the
      expression of physical dependence on opioids. Furthermore, the action on
      glutamate release might be increased by the enhancement of cAMP-dependent protein
      kinase and/or protein kinase C activity.

PMID- 9570515
TI  - A simple and sensitive ribonucleotide reductase assay.
AB  - Ribonucleotide reductase (RR) is a key regulatory enzyme in the DNA synthesis
      pathway and is the target of the cancer chemotherapeutic agent hydroxyurea. The
      study of RR is significantly hindered by the tedious and labor-intensive nature
      of enzymatic assay. In this report, we present a novel RR assay in which
      detection of the deoxyribonucleotides produced by RR occurs via coupling to the
      DNA polymerase reaction, and is enhanced by using RNase to degrade endogenous
      RNA. Cell extracts from various cell lines were treated with RNase and then
      reacted with ATP and radioactive ribonucleotide diphosphate as the substrate.
      Incorporation of the radioactive substrate [14C]CDP into DNA was linear over 30
      min and was linear with the amount of extract, which provided RR activity. The
      reaction was inhibited by hydroxyurea and required Mg2+ and ATP, suggesting that
      the assay is specific to RR activity. While RR activities determined by our
      method and by a conventional method were comparable, this novel method proved to
      be simpler, faster, more sensitive and less expensive. In addition, assay of the
      RR activity for multiple samples can easily be performed simultaneously. It is
      superior to other RR assays in all aspects.

PMID- 9570516
TI  - CD40 engagement up-regulates cyclooxygenase-2 expression and prostaglandin E2
      production in human lung fibroblasts.
AB  - A newly emerging view of fibroblasts is that they are vital for initiating
      inflammation and respond to and direct the activities of leukocytes. Human
      fibroblasts can express CD40, an activation Ag the ligand of which is displayed
      by activated leukocytes. We demonstrate here that CD40 engagement on human lung
      fibroblasts dramatically increases proinflammatory PGE2 synthesis. This up
      regulation is mediated through an induction of cyclooxygenase-2 (Cox-2) since Cox
      2-selective inhibitors block the up-regulation. Western and Northern blot
      analyses demonstrated that Cox-2 protein and mRNA are dramatically increased in
      fibroblasts following CD40 engagement. We conclude that CD40 is a major pathway
      in human fibroblasts for the induction of Cox-2. There is intense interest in
      devising strategies for disruption of the CD40-CD40 ligand system to blunt
      inflammation. Such an intervention would be expected to attenuate the up
      regulation of fibroblast Cox-2 and PGE2 production at the site of tissue injury.

PMID- 9570517
TI  - The amino-terminal Src homology 2 domain of phospholipase C gamma 1 is essential
      for TCR-induced tyrosine phosphorylation of phospholipase C gamma 1.
AB  - TCR engagement activates phospholipase C gamma 1 (PLC gamma 1) via a tyrosine
      phosphorylation-dependent mechanism. PLC gamma 1 contains a pair of Src homology
      2 (SH2) domains whose function is that of promoting protein interactions by
      binding phosphorylated tyrosine and adjacent amino acids. The role of the PLC
      gamma 1 SH2 domains in PLC gamma 1 phosphorylation was explored by mutational
      analysis of an epitope-tagged protein transiently expressed in Jurkat T cells.
      Mutation of the amino-terminal SH2 domain (SH2(N) domain) resulted in defective
      tyrosine phosphorylation of PLC gamma 1 in response to TCR/CD3 perturbation. In
      addition, the PLC gamma 1 SH2(N) domain mutant failed to associate with Grb2 and
      a 36- to 38-kDa phosphoprotein (p36-38), which has previously been recognized to
      interact with PLC gamma 1, Grb2, and other molecules involved in TCR signal
      transduction. Conversely, mutation of the carboxyl-terminal SH2 domain (SH2(C)
      domain) did not affect TCR-induced tyrosine phosphorylation of PLC gamma 1.
      Furthermore, binding of p36-38 to PLC gamma 1 was not abrogated by mutations of
      the SH2(C) domain. In contrast to TCR/CD3 ligation, treatment of cells with
      pervanadate induced tyrosine phosphorylation of either PLC gamma 1 SH2(N) or
      SH2(C) domain mutants to a level comparable with that of the wild-type protein,
      indicating that pervanadate treatment induces an alternate mechanism of PLC gamma
      1 phosphorylation. These data indicate that the SH2(N) domain is required for TCR
      induced PLC gamma 1 phosphorylation, presumably by participating in the formation
      of a complex that promotes the association of PLC gamma 1 with a tyrosine kinase.

PMID- 9570518
TI  - Differential effect of anti-B7-1 and anti-M150 antibodies in restricting the
      delivery of costimulatory signals from B cells and macrophages.
AB  - B7-1 and M150 are potent costimulatory molecules expressed on B cells and
      macrophages. We have examined the capacity of Abs against B7-1 and M150 in
      differentially inhibiting the costimulatory signals delivered by macrophages and
      B cells to OVA-specific CD4+ T cells. The anti-B7-1 Ab significantly blocked the
      proliferation of Th cells, MLR, T cell help to B cells, and secretion of IFN
      gamma when B cells were used to provide costimulation, but not when macrophages
      were used. In contrast, anti-M150 Ab significantly decreased the proliferation of
      Th cells, MLR, and production of IFN-gamma, when macrophages were utilized to
      provide costimulatory signals, but not when B cells were used as APC. However,
      when macrophages activated with IFN-gamma were used as a source of costimulation,
      like anti-M150 Ab, Ab to B7-1 also down-regulated the activation of Th cells. The
      significance of this finding is that M150 is a potent first costimulatory signal
      for initiating proliferation and secretion of IFN-gamma and providing cognate
      help for B cells by Th cells when the macrophage is used as an accessory cell.
      M150-induced IFN-gamma production induces the expression of B7-1 on the surface
      of macrophages, which then delivers a second cosignal for Th cells. B7-1 works
      efficiently when B cell provides cosignal. Both of the molecules promote Th1
      activity, as evidenced by the inhibition of the secretion of IFN-gamma but not IL
      4 by Th cells with anti-M150 and B7-1 Abs.

PMID- 9570519
TI  - Follicular dendritic cell (FDC) precursors in primary lymphoid tissues.
AB  - The origin of follicular dendritic cells (FDC) is unresolved, and as such,
      remains controversial. Based on the migration of Ag-transporting cells (ATC) into
      lymphoid follicles and the phenotypic similarity between FDC and ATC, one
      hypothesis is that ATC may represent emigrating FDC precursors. This contrasts
      with the view that FDC originate from local stromal cells in the secondary
      lymphoid tissues. Mice homozygous for the severe combined immunodeficiency
      (prkdc(scid)) mutation (scid) lack FDC. Thus, they provide a powerful tool for
      assessing de novo generation of FDC. To test whether FDC precursors could be
      found in bone marrow or fetal liver, scid/scid mice were reconstituted with
      either: 1) bone marrow cells from (BALB/c x C57BL/6)F1 donors, 2) bone marrow
      cells from ROSA BL/6 F1 (lacZ-transfected) mice, 3) rat bone marrow cells, or 4)
      rat fetal liver cells. Six to eight weeks after reconstitution with F1 bone
      marrow, cells reactive with the FDC-labeling mAb, FDC-M1, also expressed donor
      class I molecules on their surfaces. Similarly in mice reconstituted with lacZ
      transfected bone marrow cells, these cells were also positive for the lacZ gene
      product. Furthermore, in spleens of animals reconstituted with either rat bone
      marrow or rat fetal liver, rat FDC were identified using the specifically
      labeling mAb, ED5. In all cases, host FDC were also present, indicating that
      scid/scid mice have FDC precursors that will mature in the presence of allogeneic
      or xenogeneic lymphoid cells. In summary, FDC can be derived from progenitor
      cells present in primary lymphoid tissues.

PMID- 9570520
TI  - Avoidance of self-reactivity results in skewed CTL responses to rare components
      of synthetic immunogens.
AB  - In studying the CTL recognition of peptide determinants derived from the nuclear
      Ag La (SS-B), we observed significant skewing of the response toward rare
      components present within the immunogen. Thus, priming of naive mouse lymphocytes
      in vitro with a synthetic H-2Kb-binding peptide comprising human La (hLa)
      residues 51-58 resulted in class I-restricted cytotoxic T cells that failed to
      recognize naturally presented hLa 51-58 peptide. Instead, the majority of T
      hybrids recognized a low abundance (< or = 1%) contaminant present at picomolar
      concentrations in the original synthesis and identified as a peptide adduct
      containing N,4-t-butyl asparagine at position 6 of the hLa 51-58 sequence. The
      preferred T cell recognition of the butyl adduct was not due to increased
      affinity of this peptide for the H-2Kb molecule or to the antagonism of CTL
      recognizing the unmodified determinant. Rather, the bias in the immune response
      appeared to be the result of partial self-tolerance to the homologous mouse La 51
      58 determinant, which differs from its human counterpart by only a single amino
      acid at position 1 (T-->I). Accordingly, the CTL response appeared to be focused
      on "non-self" ligands present within the synthesis, even though they were present
      at very low concentrations. These observations have significant implications for
      the use of synthetic peptide vaccines, especially those designed to manipulate
      responses to self peptides such as tumor Ags in which self-tolerance may result
      in unexpected reactivity.

PMID- 9570521
TI  - Class I-restricted alloreactive cytotoxic T lymphocytes recognize a complex array
      of specific MHC-associated peptides.
AB  - A major issue in understanding alloreactive T cell responses is whether the Ags
      recognized reside in allogeneic MHC proteins themselves regardless of the
      structure of the associated peptides or whether specific peptides presented by
      allogeneic MHC proteins determine each epitope. We developed HLA-A*0201-specific
      alloreactive human CD8+ CTL lines and clones to address this issue. Acid
      treatment of HLA-A*0201+ target cells resulted in the loss of Ab-defined epitopes
      as well as recognition by all alloreactive CTL. In the presence of brefeldin A,
      no class I molecules were re-expressed at the surface of the acid-treated cells.
      Addition of a mixture of synthetic peptides corresponding to known, naturally
      processed, HLA-A*0201-associated peptides together with exogenous human beta2m
      restored binding by specific Ab but not recognition by alloreactive CTL. However,
      addition of a more complex mixture of peptides directly extracted from HLA-A*0201
      reconstituted CTL recognition. This demonstrates that these alloreactive CTL
      recognize specific peptides and not a common peptide-dependent conformation of
      HLA-A*0201. Reverse phase HPLC fractionation of the extracted peptides resulted
      in the loss of recognition by CTL lines from three individuals. This was not due
      to the loss of specific peptide species because repooling of the HPLC fractions
      led to a recovery of recognition. Furthermore, three HLA-A*0201-alloreactive CTL
      clones recognized single distinct peptide peaks from the same HPLC fractionation.
      These data suggest that the epitopes recognized in allogeneic responses to HLA
      A*0201 are complex, and the response is a result of recognition of multiple
      unique peptide-MHC complexes.

PMID- 9570522
TI  - Natural killer cell depletion fails to influence initial CD4 T cell commitment in
      vivo in exogenous antigen-stimulated cytokine and antibody responses.
AB  - The role played by NK- and NK1.1-expressing T cells in CD4 T cell activation and
      induction of immune responses in vivo is controversial. These effector cells of
      the innate immune response are hypothesized to play a pivotal role in shaping
      initial T cell activation, with some groups reporting that classical NK cells are
      required for optimal Th1-like T cell activation, and others supporting a role for
      NK1.1+ alphabeta T cells in Th2 generation. Here, we examine the impact of in
      vivo NK cell depletion on the development of exogenous Ag-specific cytokine and
      Ab responses using a murine model of human immediate hypersensitivity. OVA
      specific immune responses were induced in 1) C57Bl/6 bg/bg and bg/+ mice, 2)
      BALB/c mice pretreated with anti-asialoGM1 or control Ab, and 3) C57Bl/6 mice
      depleted of NK1.1-expressing cells by in vivo administration of anti-NK1.1 mAb
      PK136. Depletion efficacy was assessed by functional assays and flow cytometric
      analysis. Each of these approaches indicated that depletion of NK cells and
      NK1.1+ CD4+ T cells fails to alter the Th1:Th2 balance of Ag-driven cytokine
      synthesis, as indicated by OVA-stimulated cytokine synthesis in primary bulk
      culture. Similarly, the kinetics and intensity of effector responses such as OVA
      specific IgG2a and IgE synthesis were neither increased nor decreased in any of
      the three models examined. The results argue that NK cells and peripheral NK1.1+
      T cells do not play an essential role in shaping the induction of Ag-specific
      immune responses to soluble exogenous Ags, the most common class of inhalant
      allergen.

PMID- 9570523
TI  - Role of CD38 and its ligand in the regulation of MHC-nonrestricted cytotoxic T
      cells.
AB  - Human CD38 is a type II transmembrane glycoprotein that regulates lymphocyte
      adhesion, proliferation, and cytokine production. The mAb Moon-1 recognizes a
      ligand for CD38 (CD38L) and specifically inhibits CD38-mediated cell adhesion. To
      analyze the role of CD38 and its ligand in MHC-nonrestricted T cell activation,
      we examined the effects of Moon-1 and the anti-CD38 mAb IB4 on the effector
      functions of the IL-2-dependent T cell line TALL-104 (CD3/TCR-alphabeta+, CD8+,
      CD56+) and of LAK cells (90% CD3+). TALL-104 cells were almost 100% reactive with
      both mAbs, whereas the reactivity of LAK cells for IB4 and Moon-1 ranged from 10
      to 60% among different donors. From 78 to 94% of the cytotoxic CD8+/CD56+ LAK
      subset was CD38L+. Like mAb OKT3 (anti-CD3), and at variance with IB4, Moon-1
      drastically enhanced the cytotoxicity of TALL-104 and CD8+ LAK cells against a
      resistant tumor target. Granule exocytosis did not appear to play a role in Moon
      1-induced cytotoxicity. Moreover, neither IB4 nor Moon-1 induced [Ca2+]i
      mobilization in LAK and TALL-104 cells. Whereas stimulation of CD3 and CD38
      resulted in a dramatic induction of cytokine (granulocyte-macrophage-CSF, IFN
      gamma, TNF-alpha, and TNF-beta) release by both TALL-104 and LAK cells, ligation
      of CD38L was not followed by cytokine production in TALL-104 cells. Thus,
      cytotoxicity and cytokine release are independently regulated, at least in this
      system. These data demonstrate that CD38 and its ligand can regulate some T cell
      functions using signaling pathways distinct from those of CD3.

PMID- 9570524
TI  - A fusion of the EBV latent membrane protein-1 (LMP1) transmembrane domains to the
      CD40 cytoplasmic domain is similar to LMP1 in constitutive activation of
      epidermal growth factor receptor expression, nuclear factor-kappa B, and stress
      activated protein kinase.
AB  - The EBV latent infection transforming protein, LMP1, has six hydrophobic
      transmembrane domains that enable it to aggregate in the plasma membrane and a
      200-amino acid carboxyl-terminal cytoplasmic domain (CT) that activates nuclear
      factor-kappaB and induces many of the phenotypic changes in B lymphocytes that
      accompany CD40 activation. Since the phenotypic effects of LMP1 are similar to
      those of activated CD40, we now compare signaling from the LMP1 CT with that from
      the CD40 CT fused to the LMP1 transmembrane domains. The LMPCD40 chimera was
      similar to LMP1 in nuclear factor-kappaB activation and in up-regulation of
      epidermal growth factor receptor expression. CD40 ligation was known to activate
      the stress-activated protein kinase, and both LMPCD40 and LMP1 are now shown to
      induce stress-activated protein kinase activity in the absence of ligand.
      Deletion of the first four transmembrane domains of LMP1 abrogated LMP1
      aggregation in the plasma membrane and nearly abolished signaling from LMP1 or
      the LMPCD40 chimera. These results highlight the role of LMP1 as a constitutively
      active receptor similar to CD40 and provide a novel approach for the generation
      of ligand-independent receptors.

PMID- 9570525
TI  - Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine,
      chloroquine, and structurally related compounds.
AB  - Phosphorothioate oligodeoxynucleotides containing CpG (CpG-ODN) activate immune
      responses. We report that quinacrine, chloroquine, and structurally related
      compounds completely inhibit the antiapoptotic effect of CpG-ODN on WEHI 231
      murine B lymphoma cells and inhibit CpG-ODN-induced secretion of IL-6 by WEHI
      231. They also inhibit IL-6 synthesis and thymidine uptake by human
      unfractionated PBMC induced by CpG-ODN. The compounds did not inhibit LPS-induced
      responses. Half-maximal inhibition required 10 nM quinacrine or 100 nM
      chloroquine. Inhibition was noncompetitive with respect to CpG-ODN. Quinine,
      quinidine, and primaquine were much less powerful. Quinacrine was effective even
      when added after the CpG-ODN. Near-toxic concentrations of ammonia plus
      bafilomycin A1 (used to inhibit vesicular acidification) did not reduce the
      efficacy of the quinacrine, but the effects of both quinacrine and chloroquine
      were enhanced by inhibition of the multidrug resistance efflux pump by verapamil.
      Agents that bind to DNA, including propidium iodide, Hoechst dye 33258, and
      coralyne chloride did not inhibit CpG-ODN effect, nor did 4-bromophenacyl
      bromide, an inhibitor of phospholipase A2. Examination of the structure-activity
      relationship of seventy 4-aminoquinoline and 9-aminoacridine analogues reveals
      that increased activity was conferred by bulky hydrophobic substituents on
      positions 2 and 6 of the quinoline nucleus. No correlation was found between
      published antimalarial activity and ability to block CpG-ODN-induced effects.
      These results are discussed in the light of the ability of quinacrine and
      chloroquine to induce remission of rheumatoid arthritis and lupus erythematosus.

PMID- 9570526
TI  - Alloantigen-reactive Th1 development in IL-12-deficient mice.
AB  - IL-12p70, a 70- to 75-kDa heterodimer consisting of disulfide-bonded 35-kDa (p35)
      and 40-kDa (p40) subunits, enhances Th1 development primarily by its ability to
      induce IFN-gamma production by NK and Th1 cells. Although homodimers of the p40
      subunit of IL-12 are potent IL-12 receptor antagonists in some systems, we have
      reported that p40 homodimer may accentuate alloreactive CD8+ Th1 function. To
      test the role of endogenously produced p40 in alloimmunity, Th1 development was
      assessed in either IL-12 p35 knockout (p35-/-) mice, the cells of which are
      capable of secreting p40, or p40 knockout (p40-/-) mice. Compared with IL-12 wild
      type controls, splenocytes obtained from both p35-/- and p40-/- mice produced
      markedly less IFN-gamma after in vitro stimulation with Con A or alloantigens.
      Interestingly, in vivo-sensitized Th1 were detected in both p35-/- and p40-/-
      cardiac allograft recipients. However, in vivo Th1 development was enhanced in
      p35-/- recipients compared with p40-/- animals, suggesting that endogenous p40
      produced in p35-/- mice may stimulate alloreactive Th1. Indeed, neutralizing
      endogenous p40 with anti-IL-12 p40 mAb reduced Th1 development in p35-/-
      allograft recipients to that seen in p40-/- mice. To determine whether Th1
      development that occurred in the absence of IL-12p70 and p40 required IFN-gamma,
      p40-/- allograft recipients were treated with anti-IFN-gamma mAb. Neutralizing
      IFN-gamma did not inhibit in vivo Th1 development in p40-/- recipients and
      resulted in a unique pathology of rejection characterized by vascular thromboses.
      Collectively, these data suggest that 1) endogenous p40 may substitute for IL
      12p70 in alloantigen-specific Th1 sensitization in vivo and 2) in vivo
      alloreactive Th1 development may occur independent of IL-12 and IFN-gamma,
      suggesting an alternate Th1-sensitizing pathway.

PMID- 9570528
TI  - Sequestration of CD4-associated Lck from the TCR complex may elicit T cell
      hyporesponsiveness in nonobese diabetic mice.
AB  - The Lck protein tyrosine kinase associates noncovalently with the cytoplasmic
      domain of CD4. Upon ligand engagement of the TCR, CD4-associated Lck is rapidly
      activated and recruited to the TCR complex. Coupling of this complex to an
      intracellular signaling pathway may result in T cell proliferation. Previously,
      we reported that thymocytes from nonobese diabetic (NOD) mice (> or = 6 wk of
      age) exhibit a proliferative hyporesponsiveness after TCR stimulation, which is
      associated with defective TCR-mediated signaling along the protein kinase
      C/Ras/mitogen-activated protein kinase pathway of T cell activation. Here, we
      investigated whether differential association of Lck with TCR or CD4 mediates the
      control of NOD thymocyte hyporesponsiveness. We demonstrate that less CD4
      associated Lck is recruited to the TCR in activated NOD thymocytes than in
      control thymocytes. This CD4-mediated sequestration of Lck from the TCR
      correlates with the increased binding of CD4-associated Lck through its Src
      homology 2 domain to free TCRzeta and CD3gamma epsilon chains on the plasma
      membrane. Sequestration of Lck by CD4 does not occur in activated thymocytes from
      3-wk-old NOD mice and is only apparent in thymocytes from NOD mice >5 to 6 wk of
      age. This diminished recruitment of CD4-associated Lck to the TCR is not mediated
      by an increase in the amount of CD8-associated Lck. Thus, impaired recruitment of
      CD4-associated Lck to the TCR complex may represent an early event that results
      in deficient coupling of the TCR complex to downstream signaling events and gives
      rise to NOD thymocyte hyporesponsiveness.

PMID- 9570527
TI  - Autologous human monocyte-derived dendritic cells genetically modified to express
      melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement
      by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN
      alpha.
AB  - DNA-based immunization strategies designed to elicit cellular antitumor immunity
      offer an attractive alternative to protein- or peptide-based approaches. In the
      present study we have evaluated the feasibility of DNA vaccination for the
      induction of CTL reactivity to five different melanoma Ags in vitro. Cultured,
      monocyte-derived dendritic cells (DC) were transiently transfected with plasmid
      DNA encoding human MART-1/Melan-A, pMel-17/gp100, tyrosinase, MAGE-1, or MAGE-3
      by particle bombardment and used to stimulate autologous PBMC responder T cells.
      CTL reactivity to these previously identified melanoma Ags was reproducibly
      generated after two or three stimulations with genetically modified DC. Co
      ordinate transfection of two melanoma Ag cDNAs into DC promoted CTL responders
      capable of recognizing epitopes from both gene products. Coinsertion of genes
      encoding the Th1-biasing cytokines IL-12 or IFN-alpha consistently enhanced the
      magnitude of the resulting Ag-specific CTL reactivity. Importantly, DC
      transfected with a single melanoma Ag cDNA were capable of stimulating Ag
      specific CTL reactivity restricted by multiple host MHC alleles, some of which
      had not been previously identified. These results support the inherent strengths
      of gene-based vaccine approaches that do not require prior knowledge of responder
      MHC haplotypes or of relevant MHC-restricted peptide epitopes. Given previous
      observations of in situ tumor HLA allele-loss variants, DC gene vaccine
      strategies may elicit a greater diversity of host therapeutic immunity, thereby
      enhancing the clinical utility and success of such approaches.

PMID- 9570529
TI  - The Ly-49 family: regulation of cytotoxicity and cytokine production in murine
      CD3+ cells.
AB  - The Ly-49 gene families are class I-recognizing receptors on murine NK cells.
      Most Ly-49 receptors inhibit NK cell lysis upon recognizing their target class I
      ligands. In this report we have examined the ability of Ly-49A and Ly-49G2 to
      regulate T cell functions on CD3+ cells, primarily the subset that also expresses
      NK-1.1 and/or DX5. The majority (>50%) of T cells that express Ly-49 molecules
      also coexpress NK-1.1 and/or DX5, although some NK-1.1- and/or DX5-/CD3+ cells
      express Ly-49 molecules. Lysis of target cells by IL-2-cultured T cells
      expressing Ly-49A and G2 was enhanced by Abs specific for Ly-49A and G2 as well
      as by Abs to class I (H-2Dd alpha1/alpha2). Murine T cells also were cultured in
      the presence of targets that express (H-2Dd) which is inhibiting for the Ly-49A
      and G2 receptors. These cells were examined for a coincident increase in cytokine
      production (IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF). Abs to Ly-49A
      and G2 or their respective class I ligands blocked the negative signals mediated
      via the Ly-49 receptors and increased IFN-gamma and granulocyte-macrophage CSF
      production after interaction of these T cells with H-2Dd-expressing tumor
      targets. Furthermore, an EL-4 T cell line expressing both Ly-49A and G2, when
      treated with mAb YE148 and 4D11, demonstrated reduced cytokine production and
      calcium mobilization. These results demonstrate for the first time that Ly-49
      class I binding receptors, previously thought to be restricted to mouse NK cells,
      can mediate important physiological functions of T cell subsets.

PMID- 9570530
TI  - IL-12 up-regulates CD40 ligand (CD154) expression on human T cells.
AB  - IL-12 is a heterodimeric cytokine produced by APC that promotes the development
      of CD4+ Th1 cells and their IFN-gamma production after TCR/CD3 triggering. We
      here investigated the capacity of IL-12 to modify the expression on T cells of
      CD40 ligand (CD40L or CD154), a molecule transiently expressed on activated T
      cells and known to be of utmost importance for cognate interaction with B cells
      and for activation of dendritic cells and macrophages. Our data demonstrate that
      IL-12 up-regulates CD40L expression on anti-CD3-activated human peripheral blood
      T cells. For optimal induction of CD40L, IL-12 synergizes with IL-2 as well as
      with other costimulatory interactions, such as B7/CD28. The effect of IL-12 was
      observed at both the protein and the mRNA level. T cells costimulated by IL-12
      provided more efficient help for IL-4-dependent B cell proliferation and for IgG
      production than when activated in the absence of IL-12. This helper activity was
      blocked by an mAb against CD40L, indicating that the effect of IL-12 on B cells
      is mediated indirectly through CD40L. The data thus suggest that the effects of
      IL-12 on cellular and humoral immune responses are partly mediated through CD40L
      induction.

PMID- 9570531
TI  - Migration of lymphoid cells from vaginal epithelium to iliac lymph nodes in
      relation to vaginal infection by herpes simplex virus type 2.
AB  - To determine whether lymphocytes and Langerhans cells in vaginal epithelium are
      migratory, we stained mouse vaginal epithelium, including its lymphoid cells, by
      intraluminal administration of H33342, a fluorescent, vital dye. Stromal staining
      was superficial, and no free dye reached the iliac lymph nodes. The numbers and
      phenotypes of H33342-stained cells that migrated from the vagina to the iliac
      lymph nodes during the next 48 h were determined in four groups: normal mice,
      mice infected intravaginally with wild-type herpes simplex virus type 2 (HSV-2),
      mice that were immune to vaginal HSV-2 infection, and immune mice that received
      vaginal challenge with HSV-2. H33342-stained cells migrated from the vaginal
      epithelium to the iliac lymph nodes in all groups and were mainly Thy-1.2+ cells
      and B220+ cells. The number of migrating Thy-1.2+ cells was similar to the sum of
      CD4+ and CD8+ cells in all groups and was not significantly different from the
      number of CD44+ cells, suggesting that most of the migrating T cells were memory
      cells. B lymphocytes comprised 31, 32, 43, and 68% of the migrating cells in the
      four groups, respectively. We found no evidence that Langerhans cells or
      macrophages were migrating. Thus, most MHC class II+ cells in all groups were
      accounted for by B cells, and migrating cells did not express B7.1 or F4/80 or
      exhibit indented nuclei or dendritic processes. We suggest that the migrating T
      cells and B cells probably belonged to a pool of lymphocytes that recirculates
      from blood to tissues and back to the lymph nodes via their afferent lymphatics.

PMID- 9570532
TI  - Dual role of dendritic cells in the induction and down-regulation of antigen
      specific cutaneous inflammation.
AB  - We have previously reported that contact sensitivity (CS) to dinitrofluorobenzene
      (DNFB) in C57BL/6 mice was mediated by MHC class I-restricted CD8+ T cells and
      down-regulated by MHC class II-restricted CD4+ T cells. In this study, we
      analyzed the contribution of dendritic cells (DC) in the induction of these two T
      cell subsets endowed with opposite functions. Hapten-pulsed skin- and bone marrow
      derived DC, obtained from either normal C57BL/6 mice or from MHC class II (I+ II
      ) and MHC class I (I- II+)-deficient mice, were tested for their ability to prime
      normal mice for CS to dinitrofluorobenzene. Expression of MHC class I molecules
      by transferred DC was mandatory both for the induction of CS and for the
      generation of hapten-specific CD8+ T cells in lymphoid organs. I+ II- DC were as
      potent as I+ II+ DC in priming for CS, demonstrating that activation of effector
      CD8+ T cells can occur independently of CD4+ T cell help. I- II+ DC could not
      immunize for CS, although they could sensitize for a delayed-type
      hypersensitivity reaction to protein Ags. Moreover, I- II+ DC injected
      simultaneously with cutaneous sensitization down-regulated the inflammatory
      response, suggesting that hapten presentation by MHC class II molecules could
      prime regulatory CD4+ T cells. These results indicate that DC can present
      haptenated peptides by both MHC class I and class II molecules and activate Ag
      specific CD8+ effector and CD4+ regulatory T cell subsets, concurrently and
      independently.

PMID- 9570533
TI  - Differential expression of the melatonin receptor in human monocytes.
AB  - Earlier studies have shown that the pineal hormone melatonin activates human
      monocytes. It is reported here that melatonin induces the secretion of IL-1, IL
      6, and TNF in fresh and 1-day in vitro cultured monocytes that also express the
      melatonin receptor (Kd = 270 +/- 60 pM; 42,000-48,000 receptors/cell). However,
      when monocytes were cultured in vitro for 2 days, the number of receptors
      decreased to 11,000 receptors/cell, with the same Kd. LPS activation of fresh or
      1-day cultured monocytes did not result in any increase in melatonin receptor
      number. LPS activation of 2-day cultured monocytes led to an increase in the
      number of melatonin receptors, from 11,000 receptors/cell to the plateau of
      42,000 to 48,000 receptors/cell. The loss of receptors by 2-day cultured
      monocytes was not irreversible. Melatonin did not induce the release of IL-1,
      TNF, or IL-6 in monocytes cultured in vitro for 3 days and for up to 15 days, and
      these long time cultured monocytes did not express the melatonin receptors even
      after activation by LPS. The loss of melatonin receptors by monocytes cultured in
      vitro for 3 days and for up to 15 days was irreversible. Therefore, it is shown
      for the first time that human monocytes express melatonin receptors. Furthermore,
      human monocytes express melatonin receptors differentially depending on their
      state of maturation, and it appears that in vitro monocyte differentiation and
      maturation negatively affect human monocyte melatonin receptor expression.

PMID- 9570534
TI  - Cholera toxin and cholera toxin B subunit induce IgA switching through the action
      of TGF-beta 1.
AB  - Cholera toxin (CT) and its B subunit (CTB) are potent immunogens and adjuvants
      that, either alone or linked to protein Ags, can stimulate mucosal immune
      responses, modulate the induction of oral tolerance, and stimulate IgA isotype
      switching. The present studies addressed the mechanisms by which CT and CTB
      promote IgA switching. CT and rCTB, in the presence of IL-2, significantly
      increased IgA isotype switching at the clonal level in populations of purified
      and LPS-activated murine surface IgA- spleen B cells, as determined by ELISA,
      enzyme linked immunospot assays, and limiting dilution analysis. The IgA
      stimulatory effects of CT and CTB were independent of the A subunit of CT. CTB
      and CT did not increase the secretory rate of IgA-producing cells or the clonal
      burst size of IgA clones, and did inhibit B cell growth. Because TGF-beta 1 also
      inhibits B cell growth and promotes IgA switching, further studies tested whether
      the activity of CTB and CT on IgA isotype switching was mediated through TGF-beta
      1. Anti-TGF-beta Ab and soluble TGF-beta 1 type IIR inhibited CTB- and CT
      stimulated IgA isotype switching. Furthermore, increased TGF-beta 1 mRNA levels
      and bioactive TGF-beta 1, within a range shown to induce IgA isotype switching,
      were detected in cultures of surface IgA- B cells stimulated with CT or CTB and
      IL-2. These data indicate that CTB- and CT-stimulated IgA isotype switching are
      mediated through TGF-beta 1. The finding that CTB up-regulates TGF-beta 1
      activity has important implications for understanding the mechanisms by which CTB
      promotes both IgA mucosal immunity and oral tolerance.

PMID- 9570535
TI  - Polymorphism within a TCRAV family influences the repertoire through class I/II
      restriction.
AB  - Antibody-staining experiments have shown that closely related members of the
      TCRAV3 family are reciprocally selected into the CD4 or CD8 peripheral T cell
      subsets. This has been attributed to the individual AV3 members interacting
      preferentially with either MHC class I or MHC class II molecules. Single amino
      acid residues present in the complementarity-determining regions (CDR) CDR1alpha
      and CDR2alpha are important in determining MHC class specificity. We have now
      extended these observations to survey the expressed repertoire of the AV3 family
      in C57BL/6 mice. Three of the four expressed AV3 members are preferentially
      selected into the CD4+ subset of T cells. These share the same amino acid residue
      in both CDR1alpha and CDR2alpha that differ from the only CD8-skewed member.
      Preferential expression of an individual AV3 is not caused by other endogenous
      alpha- or beta-chains, by any conserved CDR3 sequence, or by the usage of TCRAJ
      regions. This study shows that residues in the CDR1 and CDR2 regions are primary
      determinants for MHC class discrimination and suggests that polymorphism found
      within a TCRAV family has an important effect on the overall shaping of the T
      cell repertoire.

PMID- 9570536
TI  - CD4+CD25+ T cells inhibit both the induction and effector function of
      autoreactive T cells and represent a unique lineage of immunoregulatory cells.
AB  - Thymectomy of susceptible strains of mice on day 3 of life results in a spectrum
      of organ-specific autoimmunity that can be prevented by reconstitution of the
      thymectomized animals early in life with normal adult lymphocytes. The effectors
      and suppressors of autoimmunity in this model have been convincingly shown to be
      CD4+ T cells. It has been demonstrated recently that the regulatory CD4+ T cells
      that prevent disease coexpress CD25. We have further characterized the population
      of CD4+CD25+ immunoregulatory cells and demonstrated that they can suppress not
      only the induction of disease post-thymectomy, but can also efficiently suppress
      disease induced by cloned autoantigen-specific effector cells. Furthermore, the
      CD4+CD25+ T cells appear to be members of a unique lineage of regulatory T cells,
      as the induction of CD25 expression on a monospecific population of T cells
      derived from TCR transgenic SCID mice did not result in suppression of post
      thymectomy autoimmunity. In addition, the TCR transgenic SCID mice were highly
      susceptible to autoimmune disease induced by the cloned line of autoantigen
      specific effectors, while normal mice were relatively resistant. The capacity of
      the cloned line to transfer disease to nu/nu recipients could be inhibited by
      normal spleen cell populations containing CD4+CD25+ cells and by purified
      CD4+CD25+ cells. Although the target Ag(s) and mechanism of action of the
      CD4+CD25+ T cells remain to be determined, it is likely that they also play an
      important role in modulating other autoimmune diseases that are mediated by
      activation of "ignorant" self-reactive T cells present in the normal peripheral
      lymphocyte pool.

PMID- 9570537
TI  - In vitro comparison of the biologic activities of monoclonal monomeric IgA,
      polymeric IgA, and secretory IgA.
AB  - Secretory IgA (S-IgA), a major humoral mediator of mucosal immunity, is a
      polymeric Ig containing an unusual extra polypeptide, secretory component (SC),
      added during transcytosis through epithelial cells. Polymeric S-IgA is more
      effective than monomeric IgA (mIgA) and IgG in neutralizing viruses. It is not
      known whether this increased efficacy is due solely to the polymeric structure of
      the molecule or whether SC itself makes S-IgA more efficient; a quantitative in
      vitro comparison of the biologic activities of S-IgA and pIgA has not been
      reported. We prepared purified pIgA and mIgA mAbs directed toward the H1
      hemagglutinin of PR8 influenza virus and purified monoclonal S-IgA (made from
      monoclonal pIgA injected into a Lewis rat and collected as S-IgA from bile) and
      compared their abilities to carry out hemagglutination inhibition (HI) and
      neutralization of the infectivity of PR8 influenza virus in vitro. The polymeric
      Igs (pIgA and S-IgA) were 5 times more effective than mIgA in HI and 7 to 10
      times more effective than mIgA in virus neutralization. Addition of SC to pIgA
      did not modify its ability to mediate HI and had only a minimal effect (S-IgA was
      1.4 times more effective) on its ability to neutralize influenza virus in vitro.
      Trypsin preincubation partially abolished mIgA- or pIgA-mediated, but not S-IgA
      mediated, viral neutralization. Thus, although S-IgA is more stable functionally
      than pIgA, the addition of SC does not influence, positively or negatively, the
      biologic activity associated with the Fab of S-IgA.

PMID- 9570538
TI  - Vascular endothelial growth factor affects dendritic cell maturation through the
      inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells.
AB  - Vascular endothelial growth factor (VEGF), produced by almost all tumor cells,
      affects the ability of hemopoietic progenitor cells (HPC) to differentiate into
      functional dendritic cells (DC) during the early stages of their maturation. In
      this study we demonstrate specific binding of VEGF to HPC. This binding was
      efficiently competed by placenta growth factor (PIGF), a ligand reportedly
      specific for the Flt-1 receptor. The number of binding sites for VEGF decreased
      during DC maturation in vitro associated with decreased levels of mRNA for Flt-1.
      VEGF significantly inhibited nuclear factor-kappa B (NF-kappa B)-dependent
      activation of reporter gene transcription during the first 24 h in culture. The
      presence of VEGF significantly decreased the specific DNA binding of NF-kappa B
      as early as 30 min after induction with TNF-alpha. This was followed on days 7 to
      10 by decreases in the mRNA for RelB and c-Rel, two subunits of NF-kappa B.
      Blockade of NF-kappa B activity in HPC at early stages of differentiation with an
      adenovirus expressing a dominant I kappa B inhibitor of NF-kappa B reproduced the
      pattern of effects observed with VEGF. Thus, NF-kappa B plays an important role
      in maturation of HPCs to DC, and VEGF activation of the Flt-1 receptor is able to
      block the activation of NF-kappa B in this system. Blockade of NF-kappa B
      activation in HPCs by tumor-derived factors may therefore be a mechanism by which
      tumor cells can directly down-modulate the ability of the immune system to
      generate effective antitumor immune responses.

PMID- 9570539
TI  - Structure, diversity, and repertoire of VH families in the Mexican axolotl.
AB  - The Mexican axolotl V(H) segments associated with the Igh C mu and C nu isotypes
      were isolated from anchored PCR libraries prepared from spleen cell cDNA. The
      eight new V(H) segments found bring the number of V(H) families in the axolotl to
      11. Each V(H) had the canonical structural features of vertebrate V(H) segments,
      including residues important for the correct folding of the Ig domain. The
      distribution of ser AGC/T (AGY) and TCN codons in axolotl V(H) genes was biased
      toward AGY in complementarity-determining region-1 (CDR1) and TCN in framework
      region-1 (FR1); there were no ser residues in the FR2 region. Thus, the axolotl
      CDR1 region is enriched in DNA sequences forming potential hypermutation hot
      spots and is flanked by DNA sequences more resistant to point mutation. There was
      no significant bias toward AGY in CDR2. Southern blotting using family-specific
      V(H) probes showed restriction fragments from 1 (V(H)9) to 11-19 (V(H)2), and the
      total number of V(H) genes was 44 to 70, depending on the restriction
      endonuclease used. The V(H) segments were not randomly used by the H mu and H nu
      chains; V(H)1, V(H)6, and V(H)11 were underutilized; and the majority of the V(H)
      segments belonged to the V(H)7, V(H)8, and V(H)9 families. Most of the nine J(H)
      segments seemed to be randomly used, except J(H)6 and J(H)9, which were found
      only once in 79 clones.

PMID- 9570541
TI  - VH mutant rabbits lacking the VH1a2 gene develop a2+ B cells in the appendix by
      gene conversion-like alteration of a rearranged VH4 gene.
AB  - We investigated the molecular basis for the appearance of V(H)a2 allotype-bearing
      B cells in mutant Alicia rabbits. The mutation arose in an a2 rabbit; mutants
      exhibit altered expression of V(H) genes because of a small deletion encompassing
      V(H)1a2, the 3'-most gene in the V(H) locus. The V(H)1 gene is the major source
      of V(H)a allotype because this gene is preferentially rearranged in normal
      rabbits. In young homozygous ali/ali animals, the levels of a2 molecules found in
      the serum increase with age. In adult ali/ali rabbits, 20 to 50% of serum Igs and
      B cells bear a2 allotypic determinants. Previous studies suggested that positive
      selection results in expansion of a2 allotype-bearing B cells in the appendix of
      young mutant ali/ali rabbits. We separated appendix cells from a 6-wk-old Alicia
      rabbit by FACS based on the expression of surface IgM and a2 allotype. The VDJ
      portion of the expressed Ig mRNA was amplified from the IgM+ a2+ and IgM+ a2-
      populations by reverse transcriptase-PCR. The cDNAs from both populations were
      cloned and sequenced. Analysis of these sequences suggested that, in a2+ B cells,
      the first D proximal functional gene in Alicia rabbits, V(H)4a2, rearranged and
      was altered further by a gene conversion-like mechanism. Upstream V(H) genes were
      identified as potential gene sequence donors; V(H)9 was found to be the most
      frequently used gene donor. Among the a2- B cells, y33 was the most frequently
      rearranged gene.

PMID- 9570540
TI  - CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation
      of I kappa B alpha and I kappa B beta and sustained activation of nuclear factor
      kappa B/c-Rel.
AB  - Unmethylated CpG dinucleotides in particular base contexts in oligonucleotides
      (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and
      apoptosis. Anti-IgM rapidly elevated the levels of NFkappaB p50/c-Rel
      heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a
      concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and
      maintained the levels of p50/c-Rel heterodimers in the presence or absence of
      anti-IgM, while control non-CpG DNA failed to induce NFkappaB activation. Anti
      IgM induced IkappaB alpha degradation followed by increased IkappaB alpha protein
      levels. The levels of IkappaB beta were increased after anti-IgM treatment. In
      contrast, CpG DNA, but not non-CpG DNA, induced sustained IkappaB alpha and
      IkappaB beta degradation in the presence or absence of anti-IgM. Inhibition of
      IkappaB degradation blocked CpG DNA-induced NFkappaB activation and expression of
      c-myc. Prevention of NFkappaB activation by inhibiting IkappaB degradation also
      suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM-induced
      apoptosis. These results indicate that CpG DNA-mediated sustained activation of
      NFkappaB depends on the degradation of IkappaB alpha and IkappaB beta and is
      required for the CpG DNA-mediated anti-apoptosis gene expression and the
      protection against anti-IgM-induced apoptosis of WEHI-231 cells.

PMID- 9570542
TI  - Biochemical and functional analyses of chromatin changes at the TCR-beta gene
      locus during CD4-CD8- to CD4+CD8+ thymocyte differentiation.
AB  - Allelic exclusion is the process wherein lymphocytes express Ag receptors from
      only one of two possible alleles, and is effected through a feedback inhibition
      of further rearrangement of the second allele. The feedback signal is thought to
      cause chromatin changes that block accessibility of the second allele to the
      recombinase. To identify the putative chromatin changes associated with allelic
      exclusion, we assayed for DNase I hypersensitivity, DNA methylation, and
      transcription in 100 kb of the TCR-beta locus. Contrary to current models, we
      identified chromatin changes indicative of an active and accessible locus
      associated with the occurrence of allelic exclusion. Of 11 DNase I hypersensitive
      sites identified, 3 were induced during CD4-CD8- to CD4+CD8+ thymocyte
      differentiation, and demethylation and increased germline transcription of the
      locus were evident. We further examined the role of the most prominently induced
      site near the TCR-beta enhancer (E beta) in allelic exclusion by targeted
      mutagenesis. Two other sites were also examined in New Zealand White (NZW) mice
      that have a natural deletion in the TCR-beta locus. TCR-beta gene recombination
      and allelic exclusion were normal in both mutant mice, negating dominant roles
      for the three hypersensitive sites in the control of allelic exclusion. The data
      suggest that alternative cis-regulatory elements, perhaps contained in the E beta
      enhancer and/or in the upstream V beta region, are involved in the control of TCR
      beta allelic exclusion.

PMID- 9570543
TI  - An intronic silencer regulates B lymphocyte cell- and stage-specific expression
      of the human complement receptor type 2 (CR2, CD21) gene.
AB  - Human CR2 (CD21) is a B lymphocyte protein whose surface expression is restricted
      primarily to the mature cell stage during development. To study the
      transcriptional mechanisms that govern cell- and stage-restricted CR2 expression,
      we first performed transient transfection analysis using constructs extending
      from -5 kb to +75 bp (-5 kb/+75) in the CR2 promoter. The promoter was found to
      be broadly active, with no evidence of cell- or stage-specific reporter gene
      expression. However, the addition of a 2.5-kb intronic gene segment (containing a
      DNase I hypersensitive site) to the (-5-kb/+75) construct resulted in appropriate
      reporter gene expression, defined as the silencing of the (-5-kb/+75) promoter
      activity only in non-CR2-expressing cells. Interestingly, appropriate reporter
      gene expression required stable transfection of the constructs in cell lines,
      suggesting nuclear matrix or chromatin interactions may be important for
      appropriate CR2 gene expression. Importantly, transgenic mice also required the
      intronic silencer to generate lymphoid tissue-specific reporter gene expression.
      Some transgenic founder lines did not demonstrate reporter gene expression,
      however, indicating that additional transcriptional regulatory elements are
      present in other regions of the CR2 gene. In summary, these data support the
      hypothesis that human CR2 expression is regulated primarily by an intronic
      silencer with lineage- and B cell stage-specific activity.

PMID- 9570544
TI  - Eosinophils bind rhinovirus and activate virus-specific T cells.
AB  - Episodes of virus-induced exacerbations of asthma are accompanied by increased
      eosinophils (EOS) in respiratory secretions and evidence of EOS degranulation.
      Although rhinoviruses (RV) are the viruses most often implicated in exacerbations
      of asthma in both children and adults, little is known about the immune response
      to this group of viruses and, in particular, EOS-RV interactions. To define such
      interactions, we incubated human rhinovirus type 16 (RV16), a serotype using ICAM
      1 as a receptor, with EOS purified from PBMC, and measured EOS-RV binding, EOS
      mediated Ag presentation and T cell activation, and EOS cell surface marker
      expression and superoxide production. Significant RV16 binding occurred to EOS
      that were pretreated with granulocyte-macrophage CSF, and this binding was
      inhibited by anti-ICAM-1 mAb. EOS also presented viral Ags to RV16-specific T
      cells, causing T cell proliferation and secretion of IFN-gamma. RV16 induced a
      significant shift from CD18dim to CD18bright, but did not affect EOS expression
      of CD54, CD69, or HLA-DR. Finally, RV16 did not induce superoxide production from
      peripheral blood EOS. These findings suggest that RV16 also binds to airway EOS,
      which resemble granulocyte-macrophage CSF-treated blood EOS in terms of high
      expression of ICAM-1. Furthermore, our findings suggest that EOS could
      participate in RV-induced immune responses through Ag presentation and T cell
      activation. By activating RV-specific T cells, EOS may play an important role in
      the initiation of antiviral T cell responses, and these effects could also
      contribute to enhanced airway inflammation and increased asthma symptoms in
      susceptible individuals.

PMID- 9570545
TI  - Protective effect on Leishmania major infection of migration inhibitory factor,
      TNF-alpha, and IFN-gamma administered orally via attenuated Salmonella
      typhimurium.
AB  - The genes encoding murine macrophage migration inhibitory factor (MIF), IL-2, IFN
      gamma or TNF-alpha were cloned individually into an expression plasmid under the
      control of the inducible promoter nirB and transfected into the aroA- aroD-
      deletion mutant strain of Salmonella typhimurium (BRD509). These S. typhimurium
      derivatives (henceforward called constructs and termed GIDMIF, GIDIL2, GIDIFN and
      GIDTNF) expressed their respective cytokines in vitro under anaerobic conditions
      and stably colonized BALB/c mice up to 14 days after oral administration. The
      highly susceptible BALB/c mice that had received the constructs orally and that
      had been subsequently infected via the footpad with Leishmania major, developed
      significantly reduced disease compared with control mice administered the
      untransfected Salmonella strain (BRD509). Importantly, a combination of GIDMIF,
      GIDIFN, and GIDTNF administered orally after L. major infection was able to
      significantly limit lesion development and reduced parasite loads by up to three
      orders of magnitude. Spleen and lymph node cells of mice administered this
      combination expressed markedly higher levels of inducible nitric oxide synthase
      (iNOS) compared with those from mice receiving an equivalent dose of the control
      strain of Salmonella (BRD509). These data therefore demonstrate the feasibility
      of therapeutic treatment in an infectious disease model using cytokines delivered
      by attenuated Salmonella. The protective effect observed correlates with the
      induction of inducible nitric oxide synthase in vivo.

PMID- 9570546
TI  - Cytokine activation leads to acidification and increases maturation of
      Mycobacterium avium-containing phagosomes in murine macrophages.
AB  - Mycobacterium avium (MAC) organisms multiply in phagosomes that have restricted
      fusigenicity with lysosomes, do not acidify due to a paucity of vacuolar proton
      ATPases, yet remain accessible to recycling endosomes. During the course of
      mycobacterial infections, IFN-gamma-mediated activation of host and bystander
      macrophages is a key mechanism in the regulation of bacterial growth. Here we
      demonstrate that in keeping with earlier studies, cytokine activation of host
      macrophages leads to a decrease in MAC viability, demonstrable by bacterial
      esterase staining with fluorescein diacetate as well as colony-forming unit
      counts from infected cells. Analysis of the pH of MAC phagosomes demonstrated
      that the vacuoles in activated macrophages equilibrate to pH 5.2, in contrast to
      pH 6.3 in resting phagocytes. Biochemical analysis of MAC phagosomes from both
      resting and activated macrophages confirmed that the lower intraphagosomal pH
      correlated with an increased accumulation of proton-ATPases. Furthermore, the
      lower pH is reflected in the transition of MAC phagosomes to a point no longer
      accessible to transferrin, a marker of the recycling endosomal system. These
      alterations parallel the coalescence of bacterial vacuoles from individual
      bacilli in single vacuoles to communal vacuoles with multiple bacilli. These data
      demonstrate that bacteriostatic and bactericidal activities of activated
      macrophages are concomitant with alterations in the physiology of the
      mycobacterial phagosome.

PMID- 9570547
TI  - Internalization of Chlamydia by dendritic cells and stimulation of Chlamydia
      specific T cells.
AB  - Chlamydia species are the causative agents of trachoma, various forms of
      pneumonia, and the most common sexually transmitted diseases. Although the
      infection cycle has been extensively characterized in epithelial cells, where the
      Chlamydia entry-vacuoles avoid fusion with host-cell lysosomes, the cellular
      immune response has received less attention. Moreover, despite the abundant
      presence of dendritic cells (DC) in the sites of infection, the interaction
      between Chlamydia and DC has never been studied. We observe that DC kill
      Chlamydia trachomatis and Chlamydia psittaci. The chlamydiae are internalized by
      the DC in a nonspecific manner through macropinocytosis, and the macropinosomes
      fuse subsequently with DC lysosomes expressing MHC class II molecules. The
      interaction induces maturation of the DC, since presentation of an exogenous Ag
      is severely inhibited after a 1-day incubation, although chlamydial Ags are still
      presented and recognized by Chlamydia-specific CD4+ T cells. Thus, DC most likely
      play a role in initiating the T cell response in vivo and could potentially be
      used in adoptive transfer therapies to vaccinate against Chlamydia.

PMID- 9570548
TI  - Requirement for in vivo production of IL-4, but not IL-10, in the induction of
      proliferative suppression by filarial parasites.
AB  - Loss of T lymphocyte proliferation and the emergence of a host response that is
      dominated by a Th2-type profile are well-established features of human
      filariasis. We have previously reported that adherent peritoneal exudate cells
      (PEC) from mice transplanted with adult Brugia malayi parasites suppress the
      proliferation of lymphocytes without blocking Ag-cytokine production in vitro. We
      now show that infection of mice with the infective larval (L3) stage of B. malayi
      generates a similar population of PEC. Suppressive cells are generated within 7
      days of infection and mediate their effects through a nitric oxide-independent
      pathway. Both L3 and adult infection elicit high levels of host IL-4 whereas the
      microfilarial stage of the parasite induces IFN-gamma production and does not
      generate a similar form of suppression. Production of host IL-4 was necessary to
      allow the generation of suppressive PEC, given that IL-4-deficient mice implanted
      with adult parasites failed to induce proliferative block. However, IL-10
      deficient mice implanted with adult parasites resulted in T cell suppression,
      indicating that IL-10 is not essential for the induction of hyporesponsiveness.
      Neither IL-4 nor IL-10 were directly responsible for ablating cellular
      proliferation in vitro, as the addition of neutralizing Ab to either cytokine did
      not reverse the proliferative block. Thus, IL-4 produced in vivo in response to
      filarial L3 and adult parasites is essential for the induction of proliferative
      suppression but is not itself the suppressive factor.

PMID- 9570549
TI  - Activation-induced T cell death exacerbates Trypanosoma cruzi replication in
      macrophages cocultured with CD4+ T lymphocytes from infected hosts.
AB  - Activation-induced cell death (AICD) of CD4+ T lymphocytes was described in
      infection with Trypanosoma cruzi, but a role for AICD in modulating parasite
      spread in host cells has not been investigated. In this study, replication of T.
      cruzi in vitro in murine macrophage (Mphi) monolayers was investigated. Long term
      (5 to 13 day) replication of infective (trypomastigote) T. cruzi forms was
      blocked by supernatants from activated (anti-TCR) CD4+ T cells of infected mice
      or by rIFN-gamma. However, when CD4+ T cells from infected mice were cocultured
      with Mphi and activated by anti-TCR, marked exacerbation of trypomastigote growth
      in Mphi ensued. The deleterious effect required contact between T cells and
      infected Mphi. Both anti-Fas and TCR activation killed a proportion of CD4+ T
      cells. Ly-6 activation did not induce AICD and did not exacerbate parasite
      growth. However, Fas-mediated killing of T cells before Ly-6 activation led to
      exacerbated parasite growth. Although a minor population, Fas-susceptible cells
      were the major source of IFN-gamma production by activated T cells. Addition of a
      neutralizing anti-Fas ligand antibody blocked 50 to 60% of CD4+ T cell AICD and
      reduced trypomastigote growth in T/Mphi cocultures stimulated by anti-TCR. The
      results demonstrate that in CD4+ T cells from infected mice, the onset of AICD
      selectively ablates IFN-gamma production and up-regulates parasite replication in
      Mphi in vitro. These findings suggest a deleterious role for AICD in T. cruzi
      infection.

PMID- 9570551
TI  - Activation of mitogen-activated protein kinase pathways by Mycoplasma fermentans
      membrane lipoproteins in murine macrophages: involvement in cytokine synthesis.
AB  - Stimulation of monocytes and resident macrophages by mycoplasmas induces
      production of numerous cytokines. We have previously reported that membrane
      lipoproteins derived from Mycoplasma fermentans are responsible for the induction
      of proinflammatory cytokines by monocytic cells and that triggering protein
      tyrosine kinase activation is an essential requirement for this biologic effect.
      In the present study, we have investigated the effect of M. fermentans-derived
      membrane lipoproteins (LAMPf) on mitogen-activated protein kinase (MAPK) cascades
      in the murine macrophage cell line RAW 264.7 and have analyzed the contribution
      of these pathways to the cytokine induction mediated by this agent. Treatment of
      murine macrophages with LAMPf resulted in significant activation of MAPK family
      members extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun NH2
      terminal kinase (JNK), and p38. Unlike LPS, these effects were demonstrated to be
      independent of the presence of serum. The activation of MAPKs paralleled the
      tyrosine kinase activation and peaked at 30 min after stimulation. The specific
      p38 inhibitor SB203580 abrogated the mycoplasma-induced IL-6, IL-1beta, and TNF
      alpha synthesis. The selective MAPK/extracellular signal-regulated kinase 1 (MEK
      1) inhibitor PD-98059 blocked both IL-1beta and TNF-alpha but not IL-6 production
      by RAW 264.7 cells in response to LAMPf. Additionally, transfection of murine
      macrophages with a JNK dominant negative mutant significantly reduced only IL-6
      production. These data underscore the role of MAPKs as signal transduction
      molecules controlling the expression of cytokines upon mycoplasma stimulation.

PMID- 9570550
TI  - Development of Th1 and Th2 populations and the nature of immune responses to
      hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine
      genes.
AB  - In this study, we provide direct evidence that the magnitude and nature of the
      immune response to a DNA vaccine can be differentially regulated by codelivery of
      various mouse cytokine genes. Mice immunized with a hepatitis B virus (HBV) DNA
      vaccine and the IL-12 or IFN-gamma gene exhibited a significant enhancement of
      Th1 cells and increased production of anti-HBV surface IgG2a Ab, as well as a
      marked inhibition of Th2 cells and decreased production of IgG1 Ab. In contrast,
      coinjection of the IL-4 gene significantly enhanced the development of specific
      Th2 cells and increased production of IgG1 Ab, whereas Th1 differentiation and
      IgG2a production were suppressed. Coinjection of the IL-2 or the granulocyte
      macrophage-CSF gene enhanced the development of Th1 cells, while the development
      of Th2 cells was not affected, and the production of IgG1 and IgG2a Ab were both
      increased. The CTL activity induced by HBV DNA vaccination was most significantly
      enhanced by codelivery of the IL-12 or IFN-gamma gene, followed by the IL-2 or
      granulocyte-macrophage-CSF gene, whereas codelivery of the IL-4 gene suppressed
      the activity. When challenged with HBV surface Ag (HBsAg)-expressing syngeneic
      tumors, significant reduction of tumor growth was observed in mice that were
      coadministered the IL-12 gene but not the IL-4 gene. Taken together, these
      results demonstrate that application of a cytokine gene in a DNA vaccine
      formulation can influence the differentiation of Th cells as well as the nature
      of an immune response and may thus provide a strategy to improve its prophylactic
      and therapeutic efficacy.

PMID- 9570552
TI  - Decreased resistance of TNF receptor p55- and p75-deficient mice to chronic
      toxoplasmosis despite normal activation of inducible nitric oxide synthase in
      vivo.
AB  - The importance of TNF-alpha in host defense to the intracellular parasite,
      Toxoplasma gondii, was investigated in mice lacking both the p55 and p75
      receptors for this cytokine. Upon i.p. infection with the avirulent ME49 strain,
      knockout mice were capable of limiting acute i.p. infection, but succumbed within
      3 to 4 wk to a fulminant necrotizing encephalitis. Receptor-deficient mice
      harbored higher cyst burdens and exhibited uncontrolled tachyzoite replication in
      the brain. The lack of TNF receptors did not adversely affect the development of
      a type 1 IFN-gamma response. In vitro studies with peritoneal macrophages
      stimulated with IFN-gamma and tachyzoites indicated that under limiting
      concentrations of IFN-gamma, nitric oxide-mediated toxoplasmastatic activity is
      TNF-alpha dependent. However, this requirement is overcome by increasing the dose
      of IFN-gamma. Furthermore, both ex vivo and in vivo studies demonstrated that
      inducible nitric oxide synthase induction in the peritoneal cavity and brain is
      unimpaired in receptor-deficient mice. Thus, TNF-dependent immune control of T.
      gondii expansion in the brain involves an effector function distinct from
      inducible nitric oxide synthase activation.

PMID- 9570553
TI  - Activation of complement by mannose-binding lectin on isogenic mutants of
      Neisseria meningitidis serogroup B.
AB  - Mannose-binding lectin (MBL) is a serum protein that has been demonstrated to
      activate the classical complement pathway and to function directly as an opsonin.
      Although MBL deficiency is associated with a common opsonic defect and a
      predisposition to infection, the role of the protein in bacterial infection
      remains unclear. We have investigated MBL binding to Neisseria meningitidis
      serogroup B1940 and three isogenic mutants, and the subsequent activation of the
      two major isoforms of C4 (C4A and C4B) by an associated serine protease, MASP.
      The mutants lacked expression of the capsular polysaccharide (siaD-), the lipo
      oligosaccharide (LOS) outer core that prevented LOS sialylation (cpsD-), or both
      capsule and LOS outer core (cps-). Using flow cytometry, it was possible to
      detect strong MBL binding to the cps- and cpsD- mutants over a wide range of
      concentrations. In contrast, minimal or no MBL binding was detected on the parent
      organism, with binding to siaD- only at higher MBL concentrations. C4 was
      activated and bound by mutants that had previously bound MBL/MASP, but there was
      no significant difference in the amounts of C4A and C4B bound. When sialic acid
      residues were removed from the parent organism by neuraminidase treatment, the
      binding of both MBL and C4 increased significantly. Our results suggest that MBL
      may bind to and activate complement on these encapsulated organisms, and the
      major determinants of these effects are the LOS structure and sialylation.

PMID- 9570554
TI  - Pre-exposure to oxidative stress decreases the nuclear factor-kappa B-dependent
      transcription in T lymphocytes.
AB  - Reactive oxygen species (ROS) are used as signaling molecules in T cell
      activation. One of the main targets of ROS is the transcription factor nuclear
      factor-kappa B (NF-kappa B). NF-kappa B-dependent transcription is inhibited by
      antioxidants, and the activation is induced or potentiated by ROS. However,
      chronic oxidative stress is known to reduce the activation of T cells and NF
      kappa B. To analyze these phenomena in more detail, we have exposed Jurkat T
      cells in vitro to oxidative stress (H2O2) at various times before or
      simultaneously with signals known to activate NF-kappa B (phorbol dibutyrate
      (PDBu) and TNF). Simultaneously applied H2O2 strongly potentiated the PDBu- or
      TNF-induced transcriptional activity of NF-kappa B. In contrast to this, H2O2
      given 3 to 20 h before the activating signal reduced NF-kappa B-dependent
      transcriptional activity. This was not due to the oxidation-induced modification
      of NF-kappa B; cytoplasmic NF-kappa B was able to bind to DNA after dissociation
      from I kappa B alpha by detergent treatment. H2O2 pre-exposure effectively
      inhibited the PDBu- or TNF-induced phosphorylation and degradation of I kappa B
      alpha, but H2O2 given simultaneously with PDBu or TNF enhanced the degradation.
      Oxidative stress was also followed by a strongly decreased ability to form
      intracellular ROS. Taken together, these data indicate that I kappa B alpha
      phosphorylation is the target of action of ROS, and as the ROS-forming capacity
      is weaker after chronic oxidative stress, I kappa B alpha is not effectively
      phosphorylated and degraded, thus leading to decreased NF-kappa B-dependent
      transcription.

PMID- 9570555
TI  - Factors involved in regulating primary and secondary immunity to infection with
      Histoplasma capsulatum: TNF-alpha plays a critical role in maintaining secondary
      immunity in the absence of IFN-gamma.
AB  - Primary infection to Histoplasma capsulatum often results in a self-limited upper
      respiratory infection in humans; however, in immunocompromised hosts,
      disseminated infection can occur through reactivation of a previous infection.
      Since disseminated histoplasmosis has emerged as a difficult clinical entity to
      treat in individuals infected with HIV, it was of interest to study the
      mechanisms involved in maintaining an effective memory immune response. It has
      been previously shown in a murine model of disseminated histoplasmosis that IL
      12, IFN-gamma, and TNF-alpha were important factors in mediating primary
      protection. To study whether these and other factors were involved in maintaining
      a protective immune response following secondary infection, normal C57BL/6 mice
      were first infected with a sublethal dose of H. capsulatum (1 x 10(5)) and then
      reinfected 3 wk later with a lethal dose of H. capsulatum (6 x 10(5)). Under
      these conditions, all mice developed an effective immune response with
      sterilizing immunity. Moreover, normal C57BL/6 mice treated with neutralizing Abs
      against either IL-12, TNF-alpha, or IFN-gamma, depleted of neutrophils or treated
      with aminoguanidine at the time of reinfection, maintained an effective immune
      response. The ability of animals to survive a secondary infection in the absence
      of IFN-gamma was verified by showing that IFN-gamma(-/-) mice previously
      immunized with H. capsulatum and treated with amphotericin B at the time of
      primary infection had prolonged survival following reinfection with a normally
      lethal dose. It was further shown that enhancement of TNF-alpha production in IFN
      gamma(-/-) mice was the major mechanism by which these mice were effective in
      controlling secondary infection.

PMID- 9570556
TI  - Immune response against large tumors eradicated by treatment with
      cyclophosphamide and IL-12.
AB  - Previous studies have demonstrated eradication of small (4-8 mm) established
      murine MCA207 sarcomas by treatment with systemic IL-12. Analysis of the
      mechanism has revealed a cellular and molecular immune response at the tumor
      typical of a Th1 cell-mediated, macrophage-effected, delayed-type
      hypersensitivity (DTH) response. In the current study we investigate the immune
      response against long term established, large MCA207 tumors induced by combined
      treatment with IL-12 and cyclophosphamide (Cy), an agent known to potentiate the
      DTH response. Our results demonstrate that s.c. large MCA207 tumors (15-20 mm)
      that are refractory to treatment by either IL-12 or Cy alone can be completely
      eradicated by the combination of Cy and IL-12. IL-12 is apparently the only
      cytokine capable of mediating tumor eradication, and the effect is dependent on
      IFN-gamma. The contribution of Cy is probably due to immunopotentiation of DTH
      rather than to direct cytotoxicity to the tumor. The regression of these large
      tumors takes >4 wk and, in many cases, is self-sustained, in that little or no
      additional IL-12 is needed beyond the initial week of administration. Analysis of
      the cellular and molecular events at the tumor site suggests that the mechanism
      is a Th1-mediated antitumor immune response.

PMID- 9570557
TI  - Induction of pulmonary allergic responses by antigen-specific Th2 cells.
AB  - The development of pulmonary allergic responses was examined in mice following
      pulmonary transfer of Ag (conalbumin)-specific Th2 cells. The levels of serum
      specific IgE, cellular infiltrates, airway mucus goblet cells, and airway
      responsiveness were analyzed and compared with those in Ag-sensitized and 
      challenged mice. Pulmonary transfer of the conalbumin-specific Th2 clone (D10)
      induced, in an Ag-specific manner, high levels of the Th2 cytokines IL-4 and IL-5
      in the bronchoalveolar lavage fluids and mucosal eosinophils, concomitant with an
      increase in airway responsiveness. The D10 cell-induced responses were seen in
      the absence of serum specific IgE. In the presence of Ag, the transferred D10
      cells not only remained in the lungs, but also increased in number 72 h post-cell
      transfer. Although significantly higher levels of IL-4 and IL-5 in the
      bronchoalveolar lavage fluids were found in D10-transferred mice, the levels of
      pulmonary eosinophilia, mucus goblet cells, and airway responsiveness were
      significantly lower than those in Ag-sensitized and -challenged mice. These
      results demonstrate that although Ag-specific activation of Th2 cells at mucosal
      sites is able to mediate the recruitment of eosinophils and the subsequent
      induction of airway hyper-responsiveness, the more severe pulmonary allergic
      responses were observed only in mice sensitized and challenged with Ag.

PMID- 9570558
TI  - CC chemokine receptors 1 and 3 are differentially regulated by IL-5 during
      maturation of eosinophilic HL-60 cells.
AB  - CC chemokine receptors 1 and 3 (CCR1 and CCR3) are expressed by eosinophils;
      however, factors regulating their expression and function have not previously
      been defined. Here we analyze chemokine receptor expression and function during
      eosinophil differentiation, using the eosinophilic cell line HL-60 clone 15 as a
      model system. RNA for CCR1, -3, -4, and -5 was not detectable in the parental
      cells, and the cells did not specifically bind CC chemokines. Cells treated with
      butyric acid acquired eosinophil characteristics; expressed mRNA for CCR1 and
      CCR3, but not for CCR4 or CCR5; acquired specific binding sites for macrophage
      inflammatory protein-1alpha and eotaxin (the selective ligands for CCR1 and CCR3,
      respectively); and exhibited specific calcium flux and chemotaxis responses to
      macrophage-inflammatory protein-1alpha, eotaxin, and other known CCR1 and CCR3
      agonists. CCR3 was expressed later and at lower levels than CCR1 and could be
      further induced by IL-5, whereas IL-5 had little or no effect on CCR1 expression.
      Consistent with the HIV-1 coreceptor activity of CCR3, HL-60 clone 15 cells
      induced with butyric acid and IL-5 fused with HeLa cells expressing CCR3-tropic
      HIV-1 envelope glycoproteins, and fusion was blocked specifically by eotaxin or
      an anti-CCR3 mAb. These data suggest that CCR1 and CCR3 are markers of late
      eosinophil differentiation that are differentially regulated by IL-5 in this
      model.

PMID- 9570560
TI  - Inflammatory agonists induce cyclooxygenase type 2 expression by human
      neutrophils.
AB  - The synthesis of prostanoids is regulated by cyclooxygenases (prostaglandin H
      synthases), which catalyze the conversion of arachidonic acid to PGH2.
      Cyclooxygenases are the target of aspirin and other nonsteroidal anti
      inflammatory agents. In this study, we found that human polymorphonuclear
      leukocytes (PMNs) express the inducible isoform of cyclooxygenase, COX-2, when
      stimulated by LPS whereas the protein was not detectable in freshly isolated
      human PMNs. We also found by immunohistochemical analysis that COX-2 is expressed
      in PMNs in inflamed human tissues. COX-2 was induced in a time- and concentration
      dependent fashion when isolated human PMNs were exposed to LPS; COX-2 was also
      induced, or its expression was increased, by TNF-alpha, IL-1, and IL-8.
      Expression of COX-2 in stimulated PMNs was paralleled by secretion of PGE2. The
      release of PGE2 was blocked by a selective nonsteroidal inhibitor of COX-2,
      indicating that the enzyme is responsible for the prostanoids produced, and was
      inhibited by dexamethasone. The time course of LPS-induced COX-2 expression and
      other features were different in freshly isolated PMNs, monocytes, and
      macrophages, indicating that COX-2 expression is differentially regulated in
      myeloid cells of different lineages and degrees of maturation. Consistent with
      this, IL-4 and IL-10, which suppressed LPS-induced COX-2 expression in monocytes,
      had little effect on this response by PMNs. These experiments demonstrate that
      PMNs express COX-2 when appropriately stimulated. Thus, they may actively
      influence the eicosanoid composition of the acute inflammatory milieu.

PMID- 9570559
TI  - Activation of protein kinase C-zeta and phosphatidylinositol 3'-kinase and
      promotion of macrophage differentiation by insulin-like growth factor-I.
AB  - Phosphoinositides that are phosphorylated at the D3 position have been reported
      to activate an atypical, Ca2-independent protein kinase C (PKC) isoform
      designated PKC-zeta, and overexpression of this enzyme leads to monocytic
      differentiation. In this study, we cultured human HL-60 promyeloid cells with
      vitamin D3 and insulin-like growth factor-I (IGF-I), a 70-amino-acid peptide that
      activates phosphatidylinositol 3'-kinase (PI 3-kinase) in murine promyeloid
      cells. Two days later, the proportion of cells differentiating into macrophages
      in serum-free medium, as assessed by expression of the alpha-subunit of the beta2
      integrin CD11b, increased from 5 +/- 1% to 25 +/- 3%. Addition of IGF-I increased
      the proportion of cells differentiating into CD11b-positive macrophages to 78 +/-
      5%. In the absence of vitamin D3, IGF-I did not induce expression of CD11b (6 +/-
      1%). The IGF-I-promoted macrophage differentiation was blocked specifically by
      preincubation of HL-60 cells with a mAb (alphaIR3) directed against the IGF type
      I receptor. Similarly, pretreatment of cells with either alphaIR3 or an IGF
      binding protein, IGFBP-3, led to a 75% inhibition of CD11b expression when cells
      were cultured with vitamin D3 in serum-containing medium. IGF-I, but not vitamin
      D3, caused a sevenfold increase in the enzymatic activity of both PI 3-kinase and
      atypical PKC-zeta. Inhibition of IGF-I-inducible PI 3-kinase with either
      wortmannin or LY294002 abrogated the IGF-I-induced activation of PKC-zeta and
      totally blocked the enhancement in macrophage differentiation caused by IGF-I.
      These data establish that PKC-zeta is a putative downstream target of PI 3-kinase
      that is activated during IGF-I-promoted macrophage differentiation.

PMID- 9570561
TI  - Alternative macrophage activation-associated CC-chemokine-1, a novel structural
      homologue of macrophage inflammatory protein-1 alpha with a Th2-associated
      expression pattern.
AB  - We have cloned a novel human CC-chemokine, alternative macrophage activation
      associated CC-chemokine (AMAC)-1. The isolated cDNA clone (803 bp) shows a single
      open reading frame of 267-bp coding for 89 amino acid residues; mature AMAC-1
      protein is predicted to consist of 69 amino acids with a m.w. of 7855. Sequence
      alignment and 3D-modeling show the typical structural characteristics of CC
      chemokines with special features in the receptor-activating domain. AMAC-1 is
      most closely related to MIP-1 alpha with a cDNA and protein sequence homology of
      55% and 59%, respectively. However, the expression pattern of AMAC-1 is directly
      opposite to that of MIP-1 alpha. While MIP-1 alpha is induced by classical
      macrophage mediators such as LPS and is inhibited by IL-4 and glucocorticoids,
      AMAC-1 is specifically induced in macrophages by alternative macrophage mediators
      such as IL-4, IL-13, and IL-10. Expression of AMAC-1 is inhibited by IFN-gamma
      while glucocorticoids exert a slightly positive synergistic effect in combination
      with IL-4. Peripheral blood monocytes do not express AMAC-1; time course
      experiments show that monocyte-to-macrophage differentiation is a prerequisite
      for AMAC-1 expression. Expression of AMAC-1 by granulocyte-macrophage CSF/IL-4
      induced, monocyte-derived dendritic cells is complex; in mature adherent
      dendritic cells, however, only minor AMAC-1 mRNA expression was found. In vivo,
      AMAC-1 is expressed by alveolar macrophages from healthy persons, smokers, and
      asthmatic patients. In conclusion, AMAC-1 is a novel CC-chemokine whose
      expression is induced in alternatively activated macrophages by Th2-associated
      cytokines; thus, AMAC-1 may be involved in the APC-dependent T cell development
      in inflammatory and immune reactions.

PMID- 9570562
TI  - Role of the mitogen-activated protein kinases in the expression of the kinin B1
      receptors induced by tissue injury.
AB  - Several cytokines and LPS regulate the population of the B1 receptors (B1Rs) for
      kinins; these are responsive to des-Arg9-bradykinin (BK) and Lys-des-Arg9-BK. B1R
      activation contributes to inflammatory vascular changes and pain. Aortic rings
      isolated from normal rabbits and incubated in vitro in Krebs physiological medium
      were used as a model of tissue injury. From a null level of response, these rings
      exhibit a time- and protein synthesis-dependent increase in the maximal
      contractile response to des-Arg9-BK. Exposure to exogenous IL-1beta or epidermal
      growth factor (EGF) considerably increases the process of sensitization to the
      kinins. Freshly isolated control aortic rings showed high mitogen-activated
      protein (MAP) kinase activities (persistent activation of p38, but less prolonged
      for extracellular signal-regulated kinase and c-Jun-N-terminal kinase/stress
      activated protein kinase pathways) relatively to the basal activities found in
      various types of cultured cells. IL-1beta or EGF further increased the activities
      of the extracellular signal-regulated kinase and c-Jun-N-terminal kinase/stress
      activated protein kinase MAP kinases. The inhibitor of the p38 MAP kinase, SB
      203580 (10 microM), massively (approximately 75%) and selectively inhibited the
      spontaneous sensitization to des-Arg9-BK over 6 h. SB 203580 also significantly
      reduced the development of the response to des-Arg9-BK as stimulated by IL-1 or
      EGF. Both spontaneous and IL-1beta-stimulated up-regulation of responsiveness to
      des-Arg9-BK were significantly inhibited by the MAP kinase extracellular signal
      regulated kinase kinase 1 inhibitor PD 98059 (approximately 40%). The protein
      kinase inhibitors failed to inhibit protein synthesis and to acutely inhibit the
      contractile effect of des-Arg9-BK, suggesting that they do not influence B1
      receptor transduction mechanisms. In cultured aortic smooth muscle cells
      stimulated with EGF, MAP kinase activation preceded B1R mRNA induction. Protein
      kinase inhibitors reveal the role of cell injury-controlled MAP kinase pathways,
      and singularly of the p38 pathway, in the induction of B1R.

PMID- 9570563
TI  - The human S100 protein MRP-14 is a novel activator of the beta 2 integrin Mac-1
      on neutrophils.
AB  - The 14-kDa myeloid-related protein (MRP-14) and its heterodimeric partner, MRP-8,
      are members of the S100 family of calcium-binding proteins (S100A9 and S100A8,
      respectively). Their importance in neutrophil function is implied by their
      unusual abundance in neutrophil cytosol (approximately 40% of cytosolic protein).
      Previous work from our laboratory has demonstrated the extracellular association
      of these proteins with vascular endothelium adjacent to transmigrating
      leukocytes. We report here a function for MRP-14 as a stimulator of neutrophil
      adhesion mediated by the beta 2 integrin, Mac-1. MRP-14 is an affinity regulator
      of Mac-1 because it promotes binding of soluble ligand and expression of an
      "activation reporter" epitope of high affinity beta 2 integrins recognized by
      mAb24. The activity of MRP-14 is confined to regulating integrin function
      because, unlike other inflammatory agonists, there was no release of L-selectin,
      up-regulation of cytosolic Mac-1, or induction of neutrophil respiratory burst or
      calcium flux. Furthermore, MRP-14 does not act as a chemoattractant or cause
      alterations in cell shape or cytoskeleton. MRP-8 has a regulatory role in MRP-14
      activity, inhibiting the adhesion induced by MRP-14 through the formation of the
      heterodimer. In terms of mechanism of action, MRP-14 does not increase Mac-1
      function by direct binding to this integrin but recognizes a distinct receptor on
      neutrophils. This receptor interaction is pertussis toxin sensitive, indicating
      that MRP-14-generated signals leading to a Mac-1 affinity increase are
      heterotrimeric G protein dependent. We postulate that MRP-14 and MRP-8 are
      important in vivo candidates for the regulated adhesion of neutrophils through
      control of Mac-1 activity.

PMID- 9570564
TI  - Angiotensin II generation at the cell surface of activated neutrophils: novel
      cathepsin G-mediated catalytic activity that is resistant to inhibition.
AB  - Human neutrophils express inducible, catalytically active cathepsin G on their
      cell surface. Herein, we report that membrane-bound cathepsin G on intact
      neutrophils has potent angiotensin II-generating activity. Membrane-bound
      cathepsin G on activated neutrophils 1) converts both human angiotensin I and
      angiotensinogen to angiotensin II; 2) expresses angiotensin II-generating
      activity equivalent to 8.6 +/- 2.3 (+/-SD) x 10(-18) mol of free cathepsin G (5.2
      +/- 1.4 x 10(6) molecules)/cell; and 3) has similar high affinity for angiotensin
      I compared with free cathepsin G (Km = 5.9 x 10(-4) and 4.6 x 10(-4) M; k(cat) =
      4.0 and 2.0/s, respectively). In marked contrast to soluble cathepsin G, membrane
      bound enzyme was substantially resistant to inhibition by plasma proteinase
      inhibitors and converted angiotensin I to angiotensin II even in undiluted
      plasma. There was a striking inverse relationship between inhibitor size and its
      effectiveness against membrane-bound cathepsin G activity. Alpha1
      antichymotrypsin was a markedly ineffective inhibitor of membrane-bound enzyme
      (IC50 = 2.18 microM and 1.38 nM when tested against 1 nM membrane-bound and free
      cathepsin G, respectively). These data indicate that membrane-bound cathepsin G
      expressed on neutrophils is an inducible and mobile angiotensin II-generating
      system that may exert potent local vasoactive and chemoattractant properties at
      sites of inflammation.

PMID- 9570565
TI  - Differences in nitric oxide production by superficial and deep human articular
      chondrocytes: implications for proteoglycan turnover in inflammatory joint
      diseases.
AB  - During inflammatory joint diseases, chondrocytes are exposed to cytokines such as
      IL-1 that induce the synthesis of nitric oxide (NO). Chondrocytes from different
      zones of the articular cartilage are known to have different metabolic
      properties. In the present study, we have demonstrated that chondrocytes
      recovered from the superficial zone of normal, human, articular cartilage
      synthesize approximately 2 to 3 times as much NO in response to IL-1 as
      chondrocytes recovered from the deep zone of the same cartilage. Production of NO
      by normal cartilage in response to IL-1 was also found to decrease with age.
      Addition of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMA, 1 mM)
      blocked NO production by cells of both zones. L-NMA completely reversed the
      suppression of proteoglycan synthesis imposed by IL-1 in deep chondrocytes, but
      produced only partial reversal in superficial cells. As noted previously, IL-1
      failed to elicit a strong catabolic response in cultures of human cartilage. In
      the presence of L-NMA, however, IL-1 reduced the metabolic t(1/2) of
      proteoglycans by approximately 50% in both the superficial and deep zones. This
      suggests that NO has, directly or indirectly, an anticatabolic effect in human
      cartilage. These data confirm the metabolic heterogeneity of human chondrocytes,
      and suggest that NO may be involved to different degrees as an endogenous
      modulator of the turnover of the cartilaginous matrix in different zones of
      articular cartilage.

PMID- 9570566
TI  - Cytokine induction of MIP-1 alpha and MIP-1 beta in human fetal microglia.
AB  - Leukocyte infiltration into the central nervous system (CNS) is a key event in
      the inflammatory processes of neuroimmunologic diseases. Microglia, resident
      macrophages of the CNS, may contribute to this process by elaborating
      chemoattractants that are capable of recruiting leukocytes across the blood-brain
      barrier. Such factors have been detected in the CNS of animal models of multiple
      sclerosis and in the brains of human and nonhuman primates with AIDS
      encephalitis. As the expression of these chemoattractants may play an important
      role in the initiation and progression of neuroimmunologic diseases, we analyzed
      expression of the chemokines MIP-1 alpha, MIP-1 beta, MCP-1, and RANTES in human
      fetal microglial cultures. Unstimulated microglia expressed minimal levels of MIP
      1 alpha, MIP-1 beta, and MCP-1, while RANTES was undetectable. In response to
      LPS, TNF-alpha, or IL-1 beta, both MIP-1 alpha and MIP-1 beta were induced at the
      mRNA and protein levels in a dose- and time-dependent manner. IFN-gamma did not
      significantly induce chemokine expression. MCP-1 was detectable in LPS- and
      cytokine-treated microglia. TGF-beta, a cytokine with down-modulatory effects on
      other cell types, had little effect on chemokine expression in microglia when
      used concomitantly before or during treatment with LPS. These results illustrate
      the ability of certain inflammatory stimuli to induce expression of MIP-1 alpha,
      MIP-1 beta, and MCP-1 by human fetal microglia. The expression of these
      chemoattractants may function to recruit inflammatory cells into the CNS during
      the course of neuroimmunologic diseases and may modulate the ability of HIV to
      infect the CNS.

PMID- 9570567
TI  - Genetic immunization against the human thyrotropin receptor causes thyroiditis
      and allows production of monoclonal antibodies recognizing the native receptor.
AB  - The generation of Abs recognizing the native structure of the human thyrotropin
      receptor (hTSHR) has been difficult because there is currently no method allowing
      the purification of correctly folded Ag in the amounts required by classical
      immunization protocols. The majority of Abs made against the hTSHR react
      preferentially with denatured molecules. We report that a humoral response
      against the native hTSHR, compatible with mAb production, is elicited in mice by
      immunization with a DNA construct encoding the receptor. BALB/c mice were
      inoculated in the anterior tibialis muscle with 100 microg of plasmid DNA
      harboring the hTSHR cDNA. Eleven weeks after the first injection, 10 mice of 14
      showed by FACS analysis a strong IgG response against the hTSHR expressed at the
      surface of Chinese hamster ovary cells. A clear TSH-binding inhibiting Ig and
      thyrotropin-blocking Ab activity (competition with TSH binding and TSH activity,
      respectively) was demonstrated in the majority of sera tested. One serum
      exhibited a clear stimulating activity. Despite the maintenance of normal
      circulating free T4 levels in all mice, these bioactivities persisted until 18
      wk, in which mice were sacrificed, their thyroids were examined histologically,
      and spleens from two animals were used for mAb production. All mice displayed a
      severe lymphocytic infiltration of their thyroids, composed mostly of activated B
      cells. Three mAbs were produced against conformational epitopes of the hTSHR. We
      conclude that genetic immunization is an efficient method of generating Abs
      recognizing the native structure of the hTSHR and a new way of inducing
      thyroiditis in mice murine.

PMID- 9570568
TI  - Streptococcal cell wall-induced arthritis: requirements for IL-4, IL-10, IFN
      gamma, and monocyte chemoattractant protein-1.
AB  - Intra-articular injection of streptococcal cell wall Ag followed by i.v.
      challenge ("reactivation") results in a destructive lymphocyte-dependent
      monoarticular arthritis. To further define the role of immune mechanisms in the
      model, Abs to Th1 and Th2-related cytokines were evaluated. Treatment of rats
      with antibodies to IL-4 reduced swelling, while treatment with anti-IL-10 or anti
      IFN-gamma either had no effect or slightly enhanced the inflammatory response.
      These results suggest that Th-2 immune mechanisms may be, at least in part,
      operative in the model. To more precisely define the role of IL-4, the effects of
      anti-IL-4 on monocyte chemoattractant protein-1 (MCP-1) expression were
      evaluated. Initial studies demonstrated that mRNA (as determined by in situ
      hybridization) and protein (as determined by immunofluorescence) for MCP-1 were
      detectable in inflamed synovial tissue in a time-dependent manner. Anti-IL-4
      treatment significantly reduced the expression of mRNA for MCP-1 24 and 72 h
      after reactivation. In addition, anti-MCP-1 inhibited swelling and reduced influx
      of (111)In-labeled T cells. These data suggest that the reactivation model of
      streptococcal cell wall Ag-induced arthritis is Th-2 dependent, and that an inter
      relationship exists between IL-4 and the expression of MCP-1.

PMID- 9570569
TI  - Subcongenic analysis of the Idd13 locus in NOD/Lt mice: evidence for several
      susceptibility genes including a possible diabetogenic role for beta 2
      microglobulin.
AB  - Although they share approximately 88% of their genome with NOD mice including the
      H2g7 haplotype, NOR mice remain free of T cell-mediated autoimmune diabetes
      (IDDM), due to non-MHC genes of C57BLKS/J (BKS) origin. NOR IDDM resistance was
      previously found to be largely controlled by the Idd13 locus within an
      approximately 24 cM segment on Chromosome 2 encompassing BKS-derived alleles for
      H3a, B2m, Il1, and Pcna. NOD stocks carrying subcongenic intervals of NOR
      Chromosome 2 were utilized to more finely map and determine possible functions of
      Idd13. NOR- derived H3a-Il1 (approximately 6.0 cM) and Il1-Pcna (approximately
      1.2 cM) intervals both contribute components of IDDM resistance. Hence, the Idd13
      locus is more complex than originally thought, since it consists of at least two
      genes. B2m variants within the H3a-Il1 interval may represent one of these.
      Monoclonal Ab binding demonstrated that dimerizing with the beta 2m(a) (NOD type)
      vs beta 2m(b) isoform (NOR type) alters the structural conformation, but not
      total expression levels of H2g7 class I molecules (e.g. Kd, Db). Beta 2m-induced
      alterations in H2g7 class I conformation may partially explain findings from bone
      marrow chimera analyses that Idd13 modulates IDDM development at the level of non
      hematopoietically derived cell types controlling selection of diabetogenic T
      cells and/or pancreatic beta cells targeted by these effectors. Since trans
      interactions between relatively common and functionally normal allelic variants
      may contribute to IDDM in NOD mice, the search for Idd genes in humans should not
      be limited to functionally defective variants.

PMID- 9570570
TI  - Liver-derived CTL in hepatitis C virus infection: breadth and specificity of
      responses in a cohort of persons with chronic infection.
AB  - Hepatitis C virus (HCV)-specific CTL have been found within the inflammatory
      infiltrate of the liver of chronically infected individuals, but the breadth and
      specificity of the CTL response in relation to viral load are less well
      characterized. In this study, we analyzed the intrahepatic CTL response in liver
      biopsy specimens from 44 chronically infected subjects. Liver-infiltrating
      lymphocytes were expanded polyclonally in bulk cultures, and multiple clones were
      derived by limiting dilution. HCV-specific CTL responses directed at genotype 1a
      structural proteins were assessed in all subjects, and 22 subjects were tested
      more comprehensively using vectors expressing all structural and nonstructural
      HCV Ags. CTL responses were further characterized to determine the HLA
      restriction and optimal epitopes recognized. In those persons screened for
      recognition of all HCV Ags, HLA class I-restricted CTL were detected in 45%.
      Nineteen different CTL epitopes were identified, which were distributed
      throughout the genome; only one epitope was targeted by more than one person. In
      those persons with CTL responses, the breadth of response ranged from one to five
      epitopes. There was no correlation between the presence of a detectable CTL
      response and viral load. These results indicate considerable heterogeneity in
      detectable HCV-specific CTL responses in chronically infected persons. The
      mechanisms by which HCV persists during chronic infection remain to be clarified.

PMID- 9570571
TI  - Cells transfected with a non-neutralizing antibody gene are resistant to HIV
      infection: targeting the endoplasmic reticulum and trans-Golgi network.
AB  - Plasmids containing single chain Fv (scFv) non-neutralizing human anti-HIV-1 gp41
      Ab cDNA, with or without endoplasmic reticulum (ER) or trans-Golgi network (TGN)
      retention signals, were constructed. Stable transfectants expressing these scFvs
      then were generated from COS-7 cells and HIV-1-susceptible CD4+ human T cells
      (Jurkat). scFv without a retention signal was secreted from cells, whereas scFv
      with an ER or TGN retention signal remained primarily within targeted
      intracellular compartments. The expression of scFv, scFv-ER, and scFv-TGN did not
      adversely affect the appearance of uninfected cells, as measured by growth rate
      or CD4 expression. Pulse-chase experiments revealed that the t(1/2) of scFv-ER
      and scFv-TGN within cells was greater than 24 h and less than 9 h, respectively.
      The scFv-ER and scFv-TGN bound HIV gp160, and the scFv-ER-gp160 and the scFv-TGN
      gp160 complexes were stable within HIV-infected transfectants. Further studies
      revealed that the maturation processing of gp160 into gp120 and gp41 was blocked
      in the scFv-ER transfectants, but not in the scFv-TGN transfectants. Moreover,
      HIV replication, as measured by p24, was inhibited by up to 99% in cells
      transfected with scFv-ER or scFv-TGN, but was not inhibited in cells transfected
      with the secretory form of scFv. It is concluded that the targeting of non
      neutralizing anti-HIV-1 Abs to specific intracellular compartments blocks HIV
      replication and represents a potential therapeutic strategy for protecting
      uninfected lymphopoietic stem cells from HIV-1-infected patients.

PMID- 9570572
TI  - Novel immunoregulatory B cell pathways revealed by lpr-+ mixed chimeras.
AB  - lpr, a murine mutation of the Fas apoptosis receptor, causes lymphadenopathy and
      autoantibody production, with lymphadenopathy primarily due to a population of
      CD4-CD8-B220+ T cells. Previous in vivo experiments, in which lpr and normal bone
      marrow cells were coinfused into lpr hosts, have demonstrated that only T cells
      of lpr origin accumulated abnormally and only B cells of lpr origin produced
      autoantibodies. Moreover, in these chimeras, B cells of normal origin were unable
      to respond to conventional, T cell-dependent exogenous Ag. To address the role of
      lpr B cells in regulation of lpr autoimmunity, we have prepared lpr-+ mixed
      chimeras and selectively eliminated lpr B cells using allele-specific, mAb
      treatment, thus allowing normal B cells to develop in an environment with lpr T
      cells. From these data, we arrived at four major conclusions: 1) Compared with
      control-treated chimeric mice, lpr B cell-depleted mice had greatly reduced total
      lymph node cell counts; 2) the T cells were derived equally from normal and lpr
      donors, and the percentage of lpr-derived CD4-CD8- T cells was greatly reduced;
      3) despite the presence of the remaining lpr T cells, no autoantibodies were
      produced by the normal derived B cells; and 4) lpr T cells without lpr B cells
      were unable to prevent a normal B cell response to conventional Ag. These data
      demonstrate that B cells can play a critical and expansive regulatory role, not
      only for T cells, but for other B cells as well.

PMID- 9570573
TI  - Mechanisms of acquired thymic tolerance in vivo: intrathymic injection of antigen
      induces apoptosis of thymocytes and peripheral T cell anergy.
AB  - Intrathymic injection of Ag induces Ag-specific tolerance in several clinically
      relevant experimental autoimmune and transplantation models. However, the exact
      mechanisms of acquired thymic tolerance in vivo remain unclear. We investigated
      the mechanisms of acquired thymic tolerance in mice that are transgenic for the
      TCR specific for peptide 323-339 of OVA. Intrathymic injection of OVA leads to
      apoptosis of thymocytes starting as early as 3 h after injection and persisting
      up to 7 days. Double positive thymocytes undergo apoptosis earlier than single
      positive thymocytes, and significantly higher percentages of double positive
      thymocytes ultimately die as compared with single positive cells. Apoptotic cells
      show decreased surface expression of CD4. In the periphery, T cells from
      intrathymically injected animals had suppressed proliferation and IL-2 production
      to OVA compared with T cells from control Ag-injected mice. We conclude that
      intrathymic injection of Ag induces apoptosis of immature thymocytes and a
      subpopulation of mature thymocytes and induces prolonged anergy in peripheral T
      cells in vivo. Understanding the mechanisms of acquired thymic tolerance may lead
      to development of novel clinical strategies to prevent autoimmune disease and
      transplant rejection.

PMID- 9570574
TI  - A non-sense mutation at Arg95 is predominant in complement 9 deficiency in
      Japanese.
AB  - Deficiency of the ninth component of complement (C9D) is one of the most common
      genetic abnormalities in Japan, with an incidence of one homozygote in 1000.
      Although C9D individuals are usually healthy, it has been shown that they have an
      significantly increased risk of developing meningococcal meningitis. In the
      present study we report the molecular bases for C9D in 10 unrelated Japanese
      subjects. As a screening step for mutations, exons 2 to 11 of the C9 gene were
      analyzed using exon-specific PCR/single-strand conformation polymorphism
      analysis, which demonstrated aberrantly migrating DNA bands in exon 4 in all the
      C9D subjects. Subsequent direct sequencing of exon 4 of the C9D subjects revealed
      that eight of the 10 C9D subjects were homozygous for a C to T transition at
      nucleotide 343, the first nucleotide of the codon CGA for Arg95, leading to a TGA
      stop codon (R95X). R95X is a novel mutation different from those recently
      identified in a Swiss family with C9D. Cases 6 and 7 were heterozygous for the
      R95X mutation. Family study in case 10 confirmed the genetic nature of the
      defect. In case 6, the second mutation for C9D of the C9 gene was identified to
      be the substitution of Cys to Tyr at amino acid residue 507 (C507Y), while the
      genetic defect(s) in the other allele in case 7 remains unknown. Our results
      indicate that a novel mutation, R95X, is present in most cases of C9D in Japan.

PMID- 9570575
TI  - Cytokine production and surface marker expression in acute and stable multiple
      sclerosis: altered IL-12 production and augmented signaling lymphocytic
      activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.
AB  - Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine
      production by PBMC, as well as expression of Th1- and Th2-associated phenotypical
      markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the
      serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis
      (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy
      controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in
      MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine
      production is increased, and IL-10 production is reduced in MS patients compared
      with those in HC, and in AMS patients compared with those in SMS; 3) whereas
      production of the metabolically active p70 heterodimers is comparable in SMS,
      AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12)
      is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and
      CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are
      increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing
      monocytes are augmented in MS compared with those in HC, and serum soluble Apo
      1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a
      complex imbalance in both cytokine production and the Fas system is present in MS
      and indicate that different cytokine profiles may be observed in patients with
      acute or stable disease. The data also suggest that peculiar phenotypic
      populations are over-represented in MS patients, and for the first time show that
      SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine
      production in human pathology.

PMID- 9570576
TI  - Intracellular and surface expression of the HIV-1 coreceptor CXCR4/fusin on
      various leukocyte subsets: rapid internalization and recycling upon activation.
AB  - We describe the expression and regulation of the HIV-1 coreceptor CXCR4/fusin.
      Using anti-CXCR4 mAb, we demonstrate that this chemokine receptor is highly
      expressed on neutrophils, monocytes, B cells, and naive T cells among peripheral
      blood cells. In secondary lymphoid organs CXCR4 was found to be expressed on B
      cells. However, individual variations with regard to surface expression could be
      observed on T cells. Expression of the receptor is not confined to the cell
      surface, as large amounts of intracellular stores can be found on various
      leukocytes. Upon activation with phorbol esters the amount of cell surface
      expressed CXCR4 on lymphocytes increases twofold within 30 s before it is
      completely down-regulated within the next 2 min. Incubation of leukocytes with
      stroma derived factor-1alpha, the natural ligand for CXCR4, induces down
      regulation of up to 60% of surface-expressed receptors in a pertussis toxin
      insensitive manner. Interestingly, receptor cross-linking caused by incubation of
      cells with anti-CXCR4 mAb triggers receptor trafficking, in that the receptor is
      rapidly internalized and recycled to the cell surface. Therefore, receptor
      internalization and recycling may regulate the functional interaction of the
      receptor with envelope proteins during an initial step of HIV-1 infection.

PMID- 9570577
TI  - Expansion of autoreactive T cells in multiple sclerosis is independent of
      exogenous B7 costimulation.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the myelinated central
      nervous system that is postulated to be induced by myelin-reactive CD4 T cells. T
      cell activation requires an antigen-specific signal through the TCR and a
      costimulatory signal, which can be mediated by B7-1 or B7-2 engagement of CD28.
      To directly examine the activation state of myelin-reactive T cells in MS, the
      costimulation requirements necessary to activate myelin basic protein (MBP) or
      tetanus toxoid (TT)-reactive CD4 T cells were compared between normal controls
      and MS patients. Peripheral blood T cells were stimulated with Chinese hamster
      ovary (CHO) cells transfected either with DRB1*1501/DRA0101 chains (t-DR2) alone,
      or in combination with, B7-1 or B7-2. In the absence of costimulation, T cells
      from normal subjects stimulated with the recall antigen TT p830-843 were induced
      to expand and proliferate, but stimulation with MBP p85-99 did not have this
      effect. In marked contrast, T cells from patients with MS stimulated with MBP p85
      99 in the absence of B7-1 or B7-2 signals expanded and proliferated. Thus, MBP
      reactive CD4 T cells in patients with MS are costimulation independent and have
      been previously activated in vivo. These experiments provide further direct
      evidence for a role of activated MBP-specific CD4 T cells in the pathogenesis of
      MS.

PMID- 9570578
TI  - Evaluation of the vocal performance of children using a voice range profile
      index.
AB  - Voice range profiles (VRPs) were analyzed according to 11 frequency, intensity,
      and morphological characteristics for 94 normal children and 136 children with
      vocal fold pathologies (ages 6-11 years). Normative data are presented showing
      marked differences between the groups. Using a specific combination of the
      child's age, the highest vocal fundamental frequency, the lowest intensity, and
      the slope of the upper VRP contour, a Voice Range Profile Index for Children
      (VRPIc) may be constructed using discriminant analysis. It is shown how the VRPIc
      can be used to screen children for vocal disorder or to quantitatively assess the
      effectiveness of voice treatment. Since the group means of the VRPIc for healthy
      and dysphonic children are scaled to +10 and -10, respectively, the VRPIc enables
      the clinician to rate a child's vocal performance with reference to healthy and
      dysphonic children in general. The sensitivity and specificity of this method was
      found to be 90% and 83%, respectively.

PMID- 9570580
TI  - Describing the consequences of disorders: stuttering and the International
      Classification of Impairments, Disabilities, and Handicaps.
AB  - The International Classification of Impairments, Disabilities, and Handicaps
      (ICIDH) proposed by the World Health Organization (WHO, 1980) can be a useful
      method for describing the experiences of individuals exhibiting speech and
      language disorders such as stuttering. Unfortunately, the definitions for the
      terms impairment, disability, and handicap that were previously presented in the
      stuttering literature have not accurately represented the true purpose of the
      ICIDH as a tool for describing the consequences of disorders. This paper reviews
      the history of these terms in the stuttering literature and proposes alternate
      definitions that are more consistent with the use of the ICIDH elsewhere in the
      field of communication disorders, as well as within the health-related
      professions in general. Based on the ICIDH framework, a model is proposed for
      discussing the outcomes of various types of stuttering treatments in the context
      of an individual's experience of the stuttering disorder, and the implications
      for treatment outcomes research using this framework are discussed.

PMID- 9570579
TI  - Effects of varied vocal intensity on ventilation and energy expenditure in women
      and men.
AB  - This study was completed to determine how ventilatory responses change by means
      of speech reading at three different sound pressure levels (SPL) as compared to
      quiet breathing prior to each task. The energy required to alter SPL was also
      studied and compared to energy expenditures during a quiet breathing condition.
      Twenty-four adults (12 women, 12 men) were studied while reading a standard
      passage at low, comfortable, and high SPLs for 7 minutes with quiet breathing
      periods between each task to achieve respiratory steady state and serve as a
      control to which the reading tasks were compared. The last 2 minutes of exhaled
      air for all speaking and quiet breathing tasks were collected using a Hans
      Rudolph mouth breathing face mask. A Sensor Medics Vmax 29 series diagnostic
      instrument system measured all ventilatory responses and energy expenditures.
      Volume and timing alterations in ventilation were characterized by measuring
      tidal volume (V[T]), inspiratory time (T[I]), inspiratory flow rate (V[T]/T[I]),
      and expiratory time (T[E]). Average ventilation, energy expenditure, and adequacy
      of ventilation were measured using minute ventilation (V[E]), oxygen consumption
      (VO2), carbon dioxide production (VCO2), and partial pressure of end-tidal carbon
      dioxide (end-tidal PET[CO2]). Results indicated volume, timing, ventilation, and
      energy expenditure values remained closest to quiet breathing values for the
      comfortable SPL. Volume, ventilation, and energy expenditure were significantly
      greater for the high SPL and lower for the low SPL, compared to the baseline
      steady state, indicating that the low SPL causes a ventilatory deficit that was
      found to be paid back at the end of the speech task during the quiet breathing
      period. These results demonstrate that an individual's comfortable SPL is the
      least energy-requiring way to speech breathe. As SPL rises above or below
      comfortable SPL, speech breathing requires more energy.

PMID- 9570581
TI  - Reprogramming phonologically similar utterances: the role of phonetic features in
      pre-motor encoding.
AB  - The effects of phonologic similarity on speech production latencies were
      investigated to explore the role of articulatory phonetic features and
      reprogramming operations during pre-motor stages of production. A form-based
      priming technique was used in five experiments to elicit rapid productions of
      single words. Subjects responded to visually presented pairs of minimally
      contrastive monosyllabic words, which varied with respect to the phonetic
      featural similarity of their onsets. Factors that were systematically manipulated
      across experiments included stimulus set size, duration of the interstimulus
      interval, and the use of feedback to subjects concerning their response
      latencies. Speech onset latencies obtained in a control condition in which no
      phonetic features were shared were compared to four other conditions in which the
      word initial phonemes of prime-target pairs did share features. Results revealed
      that shared manner was the most influential factor associated with the observed
      inhibitory phonologic similarity effect. In addition, smaller stimulus set size
      (6 words) yielded significantly slower overall response latencies than
      experiments employing larger stimulus sets (18 words). These findings suggested
      that inhibitory phonologic similarity effects did not stem from biomechanical
      constraints imposed by the articulatory system. Rather the methods employed in
      this investigation were supported as a means to investigate both the underlying
      units of representation and the processes involved in pre-motor planning apart
      from articulatory effects. The results of this investigation also supported the
      hypothesis that, during phonologic encoding, word form retrieval entails the
      selection and assembly of sublexical units into word form frames. No evidence of
      whole word retrieval during pre-motor encoding was obtained. The potential
      utility of this experimental paradigm in the investigation of pre-motor planning
      in disorders that putatively affect the processes involved in transforming word
      meaning into word form is also discussed.

PMID- 9570582
TI  - Age and volume effects on liquid swallowing function in normal women.
AB  - Understanding the nature of swallowing in persons without swallowing problems is
      a prerequisite to evaluating the nature and extent of dysphagia in persons with
      compromised swallowing. In order to determine how swallowing varies with age and
      with liquid bolus volume in women, we assessed 167 normal female swallowers
      videofluoroscopically and obtained multiple measures of swallowing function. The
      women in this study demonstrated a change in swallowing function with age, due
      primarily to an increase in pharyngeal transit and total duration of the motor
      response. The duration of closure and opening of valves in the upper
      aerodigestive tract also increased with age, and the duration of laryngeal
      elevation and hyoid movement peaked in the 60-79-year-old age groups. Bolus
      volume effects were quite consistent across most measures. As the bolus volume
      increased from 1 ml to 10 ml, transit times decreased and durations of valve
      closure and opening increased. The results of this study may be used to specify
      the relationship of swallowing function to age and liquid bolus volume in women,
      relationships that heretofore have been observed only in part and in smaller and
      more heterogeneous populations.

PMID- 9570584
TI  - Temporal-order discrimination for selected auditory and visual stimulus
      dimensions.
AB  - Thresholds for the discrimination of temporal order were determined for selected
      auditory and visual stimulus dimensions in 10 normal-adult volunteers. Auditory
      stimuli consisted of binary pure tones varying in frequency or sound pressure
      level, and visual stimuli consisted of binary geometric forms varying in size,
      orientation, or color. We determined the effect of psychophysical method and the
      reliability of performance across stimulus dimensions. Using a single-track
      adaptive procedure, Experiment 1 showed that temporal-order thresholds (TOTs)
      varied with stimulus dimension, being lowest for auditory frequency, intermediate
      for size, orientation, and auditory level, and longest for color. Test
      performance improved over sessions and the profile of thresholds across stimulus
      dimensions had a modest reliability. Experiment 2 used a double-interleaved
      adaptive procedure and TOTs were similarly ordered as in Experiment 1. However,
      TOTs were significantly lower for initially ascending versus descending tracks.
      With this method, the reliability of the profile across stimulus dimensions and
      tracks was relatively low. In Experiment 3, psychometric functions were obtained
      for each of the stimulus dimensions and thresholds were defined as the
      interpolated 70.7% correct point. The relative ordering of TOTs was similar to
      those obtained in the first two experiments. Non-monotonicities were found in
      some of the psychometric functions, with the most prominent being for the color
      dimension. A cross-experiment comparison of results demonstrates that TOTs and
      their reliability are significantly influenced by the psychophysical method.
      Taken together, these results support the notion that the temporal resolution of
      ordered stimuli involves perceptual mechanisms specific to a given sensory
      modality or submodality.

PMID- 9570583
TI  - Aided speech recognition abilities of adults with a severe or severe-to-profound
      hearing loss.
AB  - Adults with severe or severe-to-profound hearing losses constitute between 11%
      and 13.5% of the hearing-impaired population. A detailed investigation of the
      speech recognition of adults with severe (n = 20) or severe-to-profound (n = 14)
      hearing loss was conducted at The University of Melbourne. Each participant took
      part in a series of speech recognition tasks while wearing his or her currently
      fitted hearing aid(s). The assessments included closed-set tests of consonant
      recognition and vowel recognition, combined with open-set tests of monosyllabic
      word recognition and sentence recognition. Sentences were presented in quiet and
      in noise at +10 dB SNR to replicate an environment more typical of everyday
      listening conditions. Although the results demonstrated wide variability in
      performance, some general trends were observed. As expected vowels were generally
      well perceived compared with consonants. Monosyllabic word recognition scores for
      both the adults with a severe hearing impairment (M = 67.2%) and the adults with
      a severe-to-profound hearing impairment (M = 38.6%) could be predicted from the
      segmental tests, with an allowance for lexical effects. Scores for sentences
      presented in quiet showed additional linguistic effects and a significant
      decrease in performance with the addition of background noise (from 82.9% to
      74.1% for adults with a severe hearing loss and from 55.8% to 34.2% for adults
      with a severe-to-profound hearing loss). Comparisons were made between the
      participants and a group of adults using a multiple-channel cochlear implant.
      This comparison indicated that some adults with a severe or severe-to-profound
      hearing loss may benefit from the use of a cochlear implant. The results of this
      study support the contention that cochlear implant candidacy should not rely
      solely on audiometric thresholds.

PMID- 9570585
TI  - Multichannel compression, temporal cues, and audibility.
AB  - Although multichannel compression systems are quickly becoming integral
      components of programmable hearing aids, research results have not consistently
      demonstrated their benefit over conventional amplification. The present study
      examined two confounding factors that may have contributed to this inconsistency
      in results: alteration of temporal information and audibility of speech cues.
      Recognition of linearly amplified and multichannel-compressed speech was measured
      for listeners with mild-to-severe sensorineural hearing loss and for a control
      group of listeners with normal hearing. In addition to the standard speech
      signal, which provided both temporal and spectral information, the listener's
      ability to use temporal information in a multichannel compressed signal was
      directly tested using a signal-correlated noise (SCN) stimulus. This stimulus
      consisted of a time-varying speech envelope modulating a two-channel noise
      carrier. It preserved temporal cues but provided minimal spectral information.
      For each stimulus condition, short-term level measurements were used to determine
      the range of audible speech. Multichannel compression improved speech recognition
      under conditions where superior audibility was provided by the two-channel
      compression system over linear amplification. When audibility of both linearly
      amplified and multichannel-compressed speech was maximized, the multichannel
      compression had no significant effect on speech recognition score for speech
      containing both temporal and spectral cues. However, results for the SCN stimuli
      show that more extreme amounts of multichannel compression can reduce use of
      temporal information.

PMID- 9570586
TI  - Subjective judgements of clarity and intelligibility for filtered stimuli with
      equivalent speech intelligibility index predictions.
AB  - The purpose of this investigation was to determine whether subjective judgments
      of clarity or intelligibility would be rated equally among conditions in which
      speech was equated for predicted intelligibility (using the Speech
      Intelligibility Index, SII) but varied in bandwidth. Twenty listeners with normal
      hearing rated clarity and intelligibility for sentence material (Hearing In Noise
      Test) in speech-shaped noise at six paired low- and high-pass filtered conditions
      in which SII was equated for each pair. For three paired conditions, predicted
      intelligibility increased as SII increased monotonically (0.3, 0.4, 0.5). In the
      remaining paired conditions, SII continued to increase monotonically (0.6, 0.7,
      0.8) but predicted intelligibility was held at a maximal level (> or = 95%).
      Predicted intelligibility was estimated from the transfer function relating SII
      to speech recognition scores determined in preliminary experiments. Differences
      in ratings between paired low- and high-pass filtered sentences did not reach
      statistical significance for either clarity or intelligibility, indicating that
      the spectral differences at equivalent SIIs did not influence the judgments for
      either of the two dimensions. For conditions in which predicted intelligibility
      increased, both clarity and intelligibility ratings increased in a similar
      manner. For conditions in which predicted intelligibility was maximized,
      intelligibility ratings remained the same statistically across conditions while
      clarity ratings changed modestly. Although high correlations were observed
      between clarity and intelligibility ratings, intelligibility ratings were
      consistently higher than clarity ratings for comparable conditions. The results
      indicated that listeners with normal hearing produced clarity and intelligibility
      ratings for the same speech material and experimental conditions that were highly
      related but differed in magnitude. Caution is required when substituting clarity
      for intelligibility.

PMID- 9570587
TI  - Temporal analysis and stimulus fluctuation in listeners with normal and impaired
      hearing.
AB  - The first experiment investigated the effects of mild to moderate sensorineural
      hearing impairment on temporal analysis for noise stimuli of varying bandwidth.
      Tasks of temporal gap detection, amplitude modulation (AM) detection, and AM
      discrimination were examined. Relatively high levels of stimulation were used in
      order to reduce the possibility that the results of the listeners with hearing
      impairment would be influenced strongly by audibility. A general summary of
      results was that there was relatively great interlistener variation among the
      listeners with hearing impairment, with most listeners showing normal performance
      and some showing degraded performance, regardless of the bandwidth of the
      stimulus carrying the temporal information. A second experiment investigated the
      hypothesis that listeners with sensorineural hearing impairment might have poor
      gap detection due to loudness recruitment. Here, gap markers were presented at
      levels where loudness growth was steeper for the listeners with hearing
      impairment than for the listeners with normal hearing. Although gap detection was
      sometimes poorer in listeners with hearing impairment than in listeners with
      normal hearing, there was no clear relation between gap detection performance and
      loudness recruitment in listeners with mild to moderate sensorineural hearing
      impairment.

PMID- 9570588
TI  - Central auditory processing disorder in school-aged children: a critical review.
AB  - The rationale to evaluate for central auditory processing disorder (CAPD) in
      school-aged children is based on the assumption that an auditory-specific
      perceptual deficit underlies many learning problems including specific reading
      and language disabilities. A fundamental issue in this area is whether convincing
      empirical evidence exists to validate this proposition. Herein, we consider the
      issue of modality specificity by examining the extent to which reading, language,
      and attention disorders in school-aged children involve perceptual dysfunctions
      limited to a single sensory modality. Difficulty in validating CAPD as a
      diagnostic label is due in large part to use of the unimodal inclusive framework,
      which has biased the diagnosis to favor sensitivity of test results over
      documenting the specificity of the deficit. Indeed, empirical research
      documenting modality-specific auditory-perceptual dysfunction in this population
      is scarce. Therefore, the existing literature on this topic has not clarified the
      "true" nature of the problem, and has left many questions about this disorder
      unanswered. It is argued that demonstrating modality specificity is one way to
      rule out supramodal disorders as explanations for observed dysfunction.
      Multimodal perceptual testing is one logical approach to help clarify this area
      of investigation.

PMID- 9570589
TI  - Phonological skills of children with specific expressive language impairment (SLI
      E): outcome at age 3.
AB  - Naturalistic speech samples of 29 3-year-olds diagnosed with specific expressive
      language delay (SU-E) were compared to those produced by 19 age-matched normally
      developing peers in order to determine their improvement in phonological skills
      since age 2, when Rescorla and Ratner (1996) studied them. Specifically, the
      groups were compared with regard to vocalization rate, verbalizations, fully
      intelligible utterances, phonetic inventories, percentages of consonants correct
      (PCC), phonological processes, and mean length of utterance (MLU). Results
      revealed that there was no significant difference between the groups in their
      numbers of vocalizations (as there had been at age 2), although there continued
      to be differences in their phonetic inventories, PCC scores, and overall
      intelligibility. These findings suggest that at age 2 the children with SU-E were
      not only less phonologically skilled but less talkative, whereas by age 3 they
      were equally vocal. Analysis of the phonetic inventories of the children
      demonstrated that for most consonants, the SLI-E group followed the some pattern
      of development as the comparison children, but more of the normally developing
      group had productive control of each consonant, consistent with findings of
      Rescorla and Ratner. There continued to be differences in intelligibility as
      measured by rates of verbalization (those utterances with at least one
      intelligible word) and fully intelligible utterances. Using these measures, we
      found that approximately half the SU-E children had caught up with their normally
      developing peers in terms of articulation, whereas half of them continued to be
      significantly delayed. Finally, although some of the late-bloomer group had
      caught up to the comparison children in language skills, as measured by MLU, many
      had not, suggesting that there was a tendency for the children to catch up in
      some articulation skills before catching up in language abilities.

PMID- 9570590
TI  - Me or my: two different patterns of pronoun case errors.
AB  - This paper investigates why some young children prefer to replace I with me (me
      children), whereas others prefer to replace I with my (my-children). The data
      come from 12 children, observed monthly, from 1;0 to 3;0. It was found that the
      percentage of errors in which me replaced I (the me-error rate) was positively
      correlated with the correct production of me as an objective pronoun (the me
      total). The me for I and my for I errors were antagonistic, with one of the
      patterns almost always dominating over the other, resulting in a clear individual
      difference between me-children and my-children. It was also found that the me
      total during the period in which my for I replacements first emerged prefigured
      whether a child would become a me-child or a my-child.

PMID- 9570591
TI  - The development of grammatical case distinctions in the use of personal pronouns
      by Spanish-speaking preschoolers.
AB  - Data on personal pronoun development in Spanish-speaking children was obtained in
      this study. Forty monolingual Puerto Rican Spanish-speaking children between the
      ages of 2;0 and 3;11 participated in the investigation. Two tasks were designed
      to obligate production of nominative and object pronouns in both reflexive and
      non-reflexive forms. Productive use and error analysis data were obtained and
      compared to previous data on pronoun development in English. By contrast with the
      order of productive use of grammatical case distinctions reported in the
      literature for English-speaking children, the children in the present study
      demonstrated a pattern in which nominative pronoun use preceded object case use.
      Implications of these findings for developmental theories that have been
      presented to explain pronoun development are discussed.

PMID- 9570592
TI  - Language-impaired preschoolers: a follow-up into adolescence.
AB  - This paper reports a longitudinal follow-up of 71 adolescents with a preschool
      history of speech-language impairment, originally studied by Bishop and Edmundson
      (1987). These children had been subdivided at 4 years into those with nonverbal
      IQ 2 SD below the mean (General Delay group), and those with normal nonverbal
      intelligence (SLI group). At age 5;6 the SLI group was subdivided into those
      whose language problems had resolved, and those with persistent SLI. The General
      Delay group was also followed up. At age 15-16 years, these children were
      compared with age-matched normal-language controls on a battery of tests of
      spoken language and literacy skills. Children whose language problems had
      resolved did not differ from controls on tests of vocabulary and language
      comprehension skills. However, they performed significantly less well on tests of
      phonological processing and literacy skill. Children who still had significant
      language difficulties at 5;6 had significant impairments in all aspects of spoken
      and written language functioning, as did children classified as having a general
      delay. These children fell further and further behind their peer group in
      vocabulary growth over time.

PMID- 9570594
TI  - Average C-unit lengths in the discourse of African American children from low
      income, urban homes.
AB  - This investigation reports average length of communication units (C-units) in
      words and in morphemes for 95 4- to 6 1/2-year-old African American boys and
      girls from lower-income homes in metropolitan Detroit. Mean C-units increased
      across the age span of this sample, and kindergartners produced significantly
      longer C-units than preschoolers. The syntactic complexity of the children's
      language samples correlated positively with increases in C-unit length, and
      regression analyses revealed that syntactic complexity was the best predictor of
      mean C-unit length. Children with longer average C-unit lengths produced greater
      frequencies of all types of syntactic complexity. Their language samples were
      distinguished from children with shorter mean C-unit lengths by clauses linked
      with coordinate and subordinate conjunctions. The findings indicate that average
      C-unit length will be useful as a quantitative index of linguistic growth in
      research designs focusing on young school-age African American children living in
      poverty.

PMID- 9570593
TI  - Family histories of children with SLI who show extended optional infinitives.
AB  - Previous family history studies have demonstrated that there are elevated rates
      of language and language-related impairments in families identified through
      probands with language impairments. This study examines family histories of
      children with specific language impairment (SLI) known to have particular
      grammatical limitations in a core feature of grammatical acquisition, a stage
      known as Extended Optional Infinitives (EOI). Family affectedness rates are
      reported for 31 families identified through preschool probands with this clearly
      defined language impairment and 67 control families, identified through
      nonaffected preschool children developmentally similar to the probands. It was
      found that significantly more speech and language difficulties, as well as
      language-related difficulties, such as reading, were reported for proband
      families than control families. The elevated rates were obtained for nuclear
      family members and extended family members as well. Fathers of probands were more
      often reported as having difficulties (29% for speech/language impairments) than
      were mothers of probands (7%), but there was no difference between brothers (26%)
      and sisters (29%). No differences were evident between proband families based on
      proband gender. The findings are relevant for theoretical models of sources of
      unexplained variations in grammatical competence in young children. In addition,
      the findings contribute new information about expected rates of affectedness,
      means of identification of affected family members, and comorbidity of
      symptomatology.

PMID- 9570595
TI  - Performances of young African American children on two comprehension tasks.
AB  - This investigation examines the performances of 63 urban 4- to 7-year-old African
      American children from middle-income homes on two tasks designed to assess the
      development of comprehension skills. Performances on a task designed to elicit
      responses to wh-questions, and another to distinctions between active and passive
      sentence constructions, revealed grade effects and a positive relationship to
      age. The findings are discussed in terms of the appropriateness of using tasks of
      these types with young African American boys and girls who are dialect users.

PMID- 9570596
TI  - Synthetic speech comprehension: a comparison of children with normal and impaired
      language skills.
AB  - This study compared the ability of children with normal language (NL) and
      children with specific language impairment (SLI) to comprehend natural speech and
      DECtalk synthetic speech by using a sentence verification task. The effect of
      listening practice on subjects' ability to comprehend both types of speech also
      was investigated. Subjects were matched for age and sex. Mean nonverbal
      intelligence scores of the groups did not differ significantly. Results showed
      that DECtalk was significantly more difficult for all subjects to comprehend than
      was natural speech and false sentences were significantly more difficult to
      comprehend than were true sentences. Response latencies shortened significantly
      from time 1 to time 2 for all subjects. Subjects with SLI had significantly more
      difficulty comprehending both natural and synthetic speech than did subjects with
      NL. Implications these results might have for theories of the underlying cause of
      specific language impairment are discussed.

PMID- 9570597
TI  - The transurethral resection syndrome--not yet a finished story.

PMID- 9570598
TI  - Does spinal anesthesia affect cerebral oxygenation during transurethral
      prostatectomy?
AB  - BACKGROUND AND OBJECTIVES: Transurethral resection of the prostate (TURP) is
      associated with the unique complication of transurethral resection of prostate
      syndrome (TURS), which is attributed to the absorption of irrigating fluid. This
      study was initiated to investigate the effects of spinal anesthesia and TURP on
      cerebral oxygen balance. METHODS: Thirty patients scheduled for TURP were
      included. Jugular bulb oxygen saturation (SjbO2) was measured via retrograde
      cannulation of jugular venous bulb. Spinal anesthesia was initiated by 3 mL
      hyperbaric 0.5% bupivacaine injected at L3-L4 in the sitting position, producing
      a block to the T10 dermatome. Hemodynamic measurements and arterial and jugular
      bulb blood gasometry were performed before and after spinal anesthesia,
      throughout surgery, and during the postoperative period. RESULTS: A significant
      decrease of cerebral perfusion pressure after spinal anesthesia was accompanied
      by a significant decrease of SjbO2 below a preoperative value of 61% +/- 1. Eight
      patients developed yawning, irritability, restlessness, and nausea toward the end
      of surgery, and these were considered to be early signs of TURS. These patients
      demonstrated SjbO2 below 55% and 50% in 63% and 42% of respective data set
      points. CONCLUSION: The neurologic symptoms in patients undergoing TURP during
      spinal anesthesia might not only be caused by absorption of irrigating fluid but
      also by impairment of cerebral oxygenation.

PMID- 9570599
TI  - The Labat Lecture 1997--from Pauchet to today--the French connection.

PMID- 9570600
TI  - Effects of diluent volume of a single dose of epidural bupivacaine in parturients
      during the first stage of labor.
AB  - BACKGROUND AND OBJECTIVES: 0.1% bupivacaine for obstetric epidural analgesia is
      given by infusion, using a loading dose of a higher concentration alone or in
      combination with opioid analgesics. A single dose of 0.1% without any additive
      for relief of first-stage labor pain has not yet been documented. METHODS: Fifty
      eight primiparae in active labor and with less than 5 cm cervical dilatation
      received 20 mg epidural bupivacaine diluted in 4 mL [group 1: 0.5% (I)], 10 mL
      [group 2: 0.2% (II)], or 20 mL [group 3: 0.1% (III)]. Pain relief, dermatomal
      spread, and motor block were assessed. RESULTS: Visual analog pain scale (VAS)
      was significantly lower in group 2 (0.88 +/- 1.34) and group 3 (0.25 +/- 0.61)
      than in group 1 (4.37 +/- 2.57). Onset and time to maximum analgesia was
      significantly shorter in group 2 than in group 3. Mean duration of analgesia was
      120 +/- 21 minutes in group 3, 100 +/- 26 in group 2, and 43 +/- 21 in group 1.
      The mean numbers and upper limits of dermatomes blocked did not differ between
      groups 2 and 3, but were higher than in group 1. Motor blocks in groups 2 and 3
      were more extensive than in group 1 with no difference between groups 2 and 3.
      Ten mL 0.2% or 20 mL 0.1% epidural bupivacaine results in a similar degree of
      pain relief, superior to that following 4 mL 0.5%, while duration was longest
      after 20 mL 0.1%. CONCLUSIONS: Analgesia lasts significantly longer following 20
      mL 0.1% bupivacaine than following 10 mL 0.2% bupivacaine when given for first
      stage labor pain. Four milliliters 0.5% bupivacaine results in inadequate pain
      relief.

PMID- 9570601
TI  - Postoperative analgesia following total knee arthroplasty: a study comparing
      spinal anesthesia and combined sciatic femoral 3-in-1 block.
AB  - BACKGROUND AND OBJECTIVES: The quality of analgesia and subsequent morphine
      requirements following spinal anesthetic block (SAB) or combined sciatic and
      femoral (3-in-1) block (SFB) for total knee arthroplasty were compared. METHODS:
      The 39 patients studied were randomly assigned to receive either SAB (n = 19) or
      SFB (n = 20). All patients received a standardized general anesthetic, patient
      controlled analgesia, and regular diclofenac. Visual analog pain scores and
      morphine requirements were recorded for 48 hours following surgery. Observations
      were grouped into four 12-hour periods. Pain scores (0-10 cm) were expressed as
      95% confidence intervals; the criterion for analgesic success was a confidence
      interval in the range 0-3 cm. RESULTS: Although pain-free on awakening, the SAB
      patients failed to achieve analgesic success in any of the four periods, while
      the SFB patients did so in three of the four periods. Morphine consumption was
      significantly higher in the SAB group during the first two periods but similar to
      the SFB group thereafter. CONCLUSION: In comparison with SAB, SFB resulted in
      superior analgesia and reduced morphine consumption for the first 24 hours
      following total knee arthroplasty.

PMID- 9570602
TI  - Pain evaluation in the intensive care unit: observer-reported faces scale
      compared with self-reported visual analog scale.
AB  - BACKGROUND AND OBJECTIVES: The visual analog scale (VAS) is a simple and
      sensitive mean of pain assessment. The faces scale is also a simple, self
      reporting method for children. Facial signs of pain have not been used to assess
      pain in postoperative adult patients in the intensive care unit (ICU). METHODS:
      Fifty patients undergoing esophageal cancer surgery by a thoracoabdominal
      procedure were studied. Epidural opioids, such as morphine or buprenorphine,
      combined with bupivacaine were administered during and after surgery. Pain
      measurement was performed by a physician in the ICU using the self-reported VAS
      0.5, 1, 2, 4, and 6 hours after tracheal extubation and thereafter every 4 hours
      during the stay in the ICU. A nurse who was unaware of the patients' VAS scores
      assessed facial expression as a measure of pain intensity using a five-grade
      faces scale immediately before pain evaluation by VAS. The VAS was rescaled into
      five discrete units that would match the five faces scale scores. Weighted kappa
      statistics were used to establish a relative level of agreement between the five
      grade VAS and faces scale. RESULTS: Good agreement was found between the five
      grade VAS and the faces scale 30 minutes and 1 hour after tracheal extubation
      (weighted kappa values .67 and .62, respectively). The VAS and faces scales were
      measured 7-13 times per patient during the stay in the ICU, and 518 observations
      were collected. Although moderate agreement was found between the five-graded VAS
      and faces scale for all pairs of observation (weighted kappa values .54), less
      agreement was found between them in patients with moderate pain. In addition, the
      calculated mean differences between the five-graded VAS and faces scale differed
      significantly between patients. CONCLUSION: The faces scale may be useful for
      pain evaluation in the ICU.

PMID- 9570603
TI  - Intrafascicular injection of ammonium sulfate and bupivacaine in peripheral
      nerves of neonatal and juvenile rats.
AB  - BACKGROUND AND OBJECTIVES: Regional nerve blocks are often used for the treatment
      of postoperative pain in children. Ammonium sulfate is a non-narcotic anesthetic
      agent, which has been reported to provide pain relief lasting days to weeks, with
      few reported side effects in adult studies. Prior to considering clinical use in
      children, the neurotoxicity of ammonium sulfate in 4-day and 3-week old rats was
      assessed and compared with that of bupivacaine. METHODS: Each rat received a
      posterior tibial nerve intrafascicular injection (0.01 mL in 4-day-old and 0.02
      mL in 3-week-old rats) using either 10% ammonium sulfate (n = 24 per age group),
      0.5% bupivacaine (n = 18 per age group), 0.9% saline (n = 18 per age group), or
      5% phenol (n = 18 per age group). A functional assessment by serial walking track
      analysis and a morphologic assessment by neurohistology were made. RESULTS: No
      abnormalities in serial walking track analysis and no structural nerve damage
      were detected after ammonium sulfate, bupivacaine, or saline injection.
      Bupivacaine caused mild focal changes in both age groups, which recovered by 8
      weeks. CONCLUSIONS: Intrafascicular injection of ammonium sulfate was as safe as
      bupivacaine in this animal model. Further animal studies must be made before
      human trials are initiated.

PMID- 9570604
TI  - The recovery profile of hyperbaric spinal anesthesia with lidocaine, tetracaine,
      and bupivacaine.
AB  - BACKGROUND AND OBJECTIVES: Surgical procedures previously considered too lengthy
      for the ambulatory surgery setting are now being performed during spinal
      anesthesia. The complete recovery profile of tetracaine and bupivacaine are now
      of interest but are not available in the literature. This study was conducted to
      compare times to ambulation, voiding, and complete block resolution, as well as
      the incidence of back and radicular pain, after spinal anesthesia with lidocaine,
      bupivacaine, and tetracaine. METHODS: Twelve adult volunteers underwent spinal
      anesthesia on three separate occasions with three local anesthetics (lidocaine
      100 mg, bupivacaine 15 mg, and tetracaine 15 mg in hyperbaric solutions) in
      random order and in a double-blind fashion. A 24-gauge Sprotte spinal needle was
      placed at the L2-3 interspace. The level of analgesia to pinprick was determined
      moving cephalad in the midclavicular line until a dermatome was reached at which
      the prick felt as sharp as over an unblocked dermatome. One dermatome caudad to
      this point was recorded every 5 minutes as the level of analgesia. We also
      recorded the times to voiding, unassisted ambulation, and complete resolution of
      sacral anesthesia. RESULTS: There was no difference between tetracaine and
      bupivacaine in time taken for two- and four-segment regression of the analgesia
      level. However, times to ambulation and complete resolution of the block were
      significantly shorter with bupivacaine then with tetracaine. With lidocaine,
      times to four-segment regression, ambulation, voiding, and complete regression of
      the block were significantly shorter than with bupivacaine and tetracaine. Time
      to two-segment regression did not differ among local anesthetics. Back and
      radicular pain symptoms were reported by three subjects after lidocaine
      subarachnoid block but not after tetracaine or bupivacaine. CONCLUSION: Among
      individual subjects, lidocaine exhibited the shortest recovery profile. However,
      the recovery profiles of the three anesthetics were very variable between
      subjects. Time to meeting discharge criteria after bupivacaine or tetracaine was
      faster in a few subjects than that after lidocaine in other subjects. For
      ambulatory anesthesia, times to two- and four-segment regression do not
      accurately predict time to readiness for discharge after spinal anesthesia.

PMID- 9570605
TI  - A comparative study of low-dose hyperbaric spinal lidocaine 0.5% versus 5% for
      continuous spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Concerns of cauda equina syndrome have discouraged
      clinicians to use 5% lidocaine for continuous spinal anesthesia. Earlier reports
      indicated that single-shot spinal lidocaine 0.5% is effective for minor
      gynecologic and perianal surgery. In the present study, we evaluate the
      anesthetic and hemodynamic effects of low dose hyperbaric 0.5% lidocaine for
      continuous spinal anesthesia and compare with those of the 5% lidocaine solution
      in patients undergoing urologic surgery. METHODS: Spinal anesthesia was induced
      via an indwelling subarachnoid catheter in 42 elderly male patients (range, 57-84
      years) undergoing transurethral prostate and bladder procedures. Patients were
      randomly assigned to receive an initial 30-mg bolus of hyperbaric lidocaine in
      the form of either 6 mL of 0.5% solution or 0.6 mL of 5% solution. Additional 30
      mg boluses (to a total of 90 mg) were given, if necessary, to establish initial
      sensory block to T10 or higher and lower limb paralysis. Supplemental doses of 30
      mg or less were given during surgery, as needed. Dermatomal level of sensory
      anesthesia and degree of motor blockade were assessed at regular intervals by a
      blinded observer. Heart rate and blood pressure (mean systolic and diastolic)
      values were monitored at regular intervals. RESULTS: Forty patients were studied
      successfully. Both hyperbaric 0.5% and 5% lidocaine provided adequate surgical
      anesthesia in 75% (30/40) of patients after a single 30-mg dose. A median peak
      sensory level of T5 (range, T2-T9) achieved within 11.1 +/- 4.5 minutes in
      patients receiving the 0.5% solution was significantly higher than the peak
      sensory level of T7 (range, T4-T12) in the 5% group (P = .043). The duration of
      surgical anesthesia after a 30-mg dose was similar in both groups--48.1 +/- 12.1
      minutes versus 50.8 +/- 16.5 minutes respectively. Of the 30 patients (15 in each
      group) who received 30 mg initially, 25 required repeat lidocaine dosing through
      the catheter during surgery. The maximum decrease in heart rate and blood
      pressure values was within 10% and 20%, respectively, of baseline values in both
      groups. In the remaining patients (10/40), anesthesia was achieved successfully
      in five patients in the 0.5% group and three patients in the 5% group after two
      30-mg lidocaine boluses (60 mg) and two patients in the 5% group after three 30
      mg boluses (90 mg). CONCLUSIONS: Continuous spinal anesthesia produced by 0.5%
      lidocaine with 7.5% dextrose is as effective as that produced by the 5% lidocaine
      solution in elderly patients undergoing urologic surgery. An initial 30-mg bolus
      delivered via indwelling subarachnoid catheter was sufficient to achieve surgical
      anesthesia for approximately 50 minutes in most patients. Hemodynamic effects of
      the two lidocaine solutions were also comparable.

PMID- 9570606
TI  - Spinal anesthesia with tetracaine in 0.75% glucose: influence of the vertebral
      interspace used for injection.
AB  - BACKGROUND AND OBJECTIVES: The anesthetic behavior and hemodynamic consequences
      of spinal anesthesia with marginally hyperbaric tetracaine containing a low
      concentration of glucose injected at two different interspaces were examined and
      compared with those of conventionally hyperbaric solution. METHODS: One-hundred
      twenty ASA Physical Status I or II patients scheduled for elective surgery to the
      lower limb were sequentially assigned to one of three equal groups to receive
      spinal anesthesia: Group 1 received 0.5% tetracaine in 0.75% glucose with 0.125%
      phenylephrine at the L2-L3 interspace; group 2 0.5% tetracaine in 0.75% glucose
      with 0.125% phenylephrine at the L3-L4 interspace; group 3 0.5% tetracaine in
      7.5% glucose with 0.125% phenylephrine at the L3-L4 interspace. Neural block was
      assessed in a double-blinded manner by cold, pinprick, and touch sensation, and a
      modified Bromage scale after the injection of the study drug. RESULTS: Injection
      at the L2-L3 interspace produced significantly higher spread of analgesia [median
      T7 (10th, 90th percentiles T10, T4)] than injection at L3-L4 interspace [T10 (L1,
      T5)] when using the solution in 0.75% glucose. There were no significant
      differences in peak dermatomal levels between groups 1 and 3, but the number of
      patients who required ephedrine for the treatment of hypotension was larger in
      group 3. CONCLUSIONS: A marginally hyperbaric tetracaine solution injected at the
      L2-L3 interspace with the patient in the lateral position produced greater extent
      of cephalad spread than that at the L3-L4 interspace. When compared to a
      conventionally hyperbaric tetracaine solution injected at the L3-L4 interspace,
      the marginally hyperbaric solution injected at the L2-L3 interspace caused less
      hemodynamic variability despite similar levels of maximum sensory block.

PMID- 9570607
TI  - Alkalinizing water-soluble local anesthetic solutions by addition of
      cyclodextrin.
AB  - BACKGROUND AND OBJECTIVES: The use of sodium bicarbonate for alkalinization of
      local anesthetics to improve their efficacy has some disadvantages including
      decreased stability of the solutions. The present study was performed to evaluate
      usefulness of cyclodextrins (CDs) in improving the solubility and stability of
      local anesthetic solutions at near physiologic pH without precipitation. METHODS:
      Solubility of local anesthetics with or without CDs in physiologic saline was
      investigated by monitoring cloudiness or precipitate formation visually and by
      recording absorbance at 620 nm. Interaction of anesthetic and CD was also studied
      spectrophotometrically using spectral change of the drugs associated with the
      inclusion complex formation. RESULTS: Cyclodextrins improved the solubility and
      stability of the four local anesthetics studied (dibucaine, tetracaine,
      bupivacaine, and lidocaine). In the neutral pH region, the effects of the CDs
      were more significant with dibucaine and tetracaine, which are more hydrophobic
      than the other two. A type of effective CD was different for each anesthetic
      depending partly on the tendency to form inclusion complex with local anesthetic.
      The local anesthetic solutions solubilized by CDs were found to remain clear for
      more than 72 hours without any visible precipitation or turbidity at neutral pHs.
      CONCLUSIONS: The improved solubility of local anesthetics by adding CD may be
      caused by inclusion complex formation of CD with local anesthetics. This new
      preparation for the alkalinized water-soluble anesthetic solutions may be useful
      for practical application in the clinical setting, although this awaits further
      study.

PMID- 9570609
TI  - High-dose ropivacaine wound infiltration for pain relief after inguinal hernia
      repair: a clinical and pharmacokinetic evaluation.
AB  - BACKGROUND AND OBJECTIVES: Early data on ropivacaine, a recently introduced local
      anesthetic, indicate a longer duration of skin analgesia than with bupivacaine,
      along with lower toxicity. The objective of this study was to evaluate
      ropivacaine 7.5 mg/mL for wound infiltration pain relief after hernia surgery, in
      higher doses than used before, in an open, nonrandomized design. METHODS: Twenty
      otherwise healthy men underwent elective unilateral open hernia repair by the
      same surgeon. General anesthesia was used during surgery, and infiltration of the
      operating field with 300 mg (n = 10) or 375 mg (n = 10) ropivacaine, 7.5 mg/mL,
      was employed for postoperative pain relief. Any sign of an adverse event was
      recorded. Plasma concentrations of ropivacaine were monitored. Pain at rest and
      on mobilization was regularly assessed over 24 hours by a visual analog scale.
      Patients' ability to walk and void and the need for supplementary analgesics were
      recorded. RESULTS: No serious adverse effects occurred. Plasma concentrations
      showed large variations but no toxic levels. No significant differences between
      the two groups were detected in pain scores which were low in both groups, at
      rest or on mobilization, or in the consumption of supplementary analgesics. At 4
      hours, 19 patients were able to walk. Within 8 hours of surgery, all patients had
      passed urine without any problem. Wound healing was normal. CONCLUSIONS:
      Infiltration of ropivacaine 7.5 mg/mL during hernia surgery can be employed
      safely in doses of 300 mg and 375 mg to control pain after hernia surgery. The
      lower dose is recommended, since the higher one did not give any clinically
      relevant advantages.

PMID- 9570608
TI  - Addition of bupivacaine to sufentanil in patient-controlled epidural analgesia
      after lower limb surgery in young adults: effect on analgesia and micturition.
AB  - BACKGROUND AND OBJECTIVES: The usefulness of adding bupivacaine to an opioid
      administered by the epidural route is controversial. This study examines both the
      quality of pain relief and side effects, in particular urinary retention, during
      patient-controlled epidural analgesia (PCEA) with sufentanil alone or in
      combination with two different concentrations of bupivacaine. METHODS: In a
      double-blind randomized study, 60 healthy young adults undergoing open knee or
      ankle surgery with combined spinal-epidural anesthesia received postoperative
      analgesia via PCEA with sufentanil alone or with 0.06% or 0.12% bupivacaine. In
      addition to pain scores at rest and during mobilization, bladder function was
      evaluated. Strict criteria were respected in scoring the occurrence of problems
      suggestive of urinary retention. The 24-hour analgesic consumption and the
      incidence of other side effects were also recorded. RESULTS: Patients receiving
      bupivacaine had better pain relief than those receiving only the opioid, but this
      difference was more pronounced when measuring dynamic pain scores. The
      consumption of sufentanil was significantly higher in the group receiving the
      opioid alone than in the group receiving 0.06% bupivacaine. The bupivacaine dose
      requirements were twice as high with the 0.12% concentration. Bladder problems
      occurred significantly more frequently in patients treated with the highest
      bupivacaine concentration. Motor impairment was not a major problem. CONCLUSIONS:
      A 0.06% bupivacaine-sufentanil combination offered the best results in terms of
      analgesic quality and lower side effects, mainly micturition problems, which may
      be explained by the higher consumption of local anesthetic at the higher
      bupivacaine concentration. Analgesic quality could not be improved by increasing
      the bupivacaine concentration.

PMID- 9570611
TI  - Combined spinal and epidural analgesia in a parturient with severe myasthenia
      gravis.
AB  - BACKGROUND AND OBJECTIVES: A 27-year-old woman with a history of myasthenia
      gravis presented for vaginal delivery. METHODS: A combined spinal epidural was
      initiated with 7.5 microg intrathecal sufentanil at the time of first request for
      analgesia followed by 140 mg epidural lidocaine prior to spontaneous vaginal
      delivery. RESULTS: The patient had a pain-free spontaneous vaginal delivery
      uncomplicated by muscle weakness. CONCLUSION: Combined spinal and epidural
      anesthesia using intrathecal opioids initially provides labor analgesia with
      minimal muscle weakness in the parturient with myasthenia gravis.

PMID- 9570610
TI  - The peripheral analgesic effect of meperidine in reducing propofol injection pain
      is not naloxone-reversible.
AB  - BACKGROUND AND OBJECTIVES: Meperidine is frequently used in general anesthesia
      and perioperative analgesia. In addition to its opioid action, meperidine
      possesses some local anesthetic properties. A preliminary study using the
      tourniquet venous retention technique found meperidine to be more effective in
      reducing propofol injection pain than fentanyl or morphine, both of which were
      slightly better than placebo. This study was undertaken to evaluate whether this
      peripheral analgesic effect of meperidine is affected by naloxone. METHODS: In a
      randomized, double-blind manner, after venous occlusion with a tourniquet,
      meperidine 40 mg was given intravenously to patients in group A (n = 31),
      meperidine 40 mg followed by naloxone 0.04 mg to group B (n = 32), meperidine 40
      mg followed by naloxone 0.2 mg to group C (n = 30), and normal saline placebo to
      group D (n = 30). The venous retention of drug(s) was maintained for 1 minute,
      followed by tourniquet release and intravenous administration of propofol 100 mg.
      Pain assessment was made immediately after the propofol injection. RESULTS: All
      three groups given meperidine had significantly less propofol injection pain (P <
      .01 ) than the group given saline placebo, and there was no difference among
      groups A, B, and C. CONCLUSION: The peripheral analgesic effect of meperidine in
      reducing propofol injection pain is not mediated by its opioid activity.

PMID- 9570612
TI  - Severe preeclampsia complicating mitral valve stenosis.
AB  - BACKGROUND AND OBJECTIVES: We present a report of a parturient with severe mitral
      valve stenosis diagnosed during a previous pregnancy who developed severe
      preeclampsia. METHODS: Labor and subsequent abdominal delivery were managed with
      epidural analgesia and anesthesia. The clinical management was guided by invasive
      hemodynamic monitoring, including a flow-directed pulmonary artery catheter.
      CONCLUSIONS: Peripartum maternal and neonatal outcomes were satisfactory.
      Postpartum complications included pulmonary edema as well as peripartum heart
      failure and pulmonary thromboembolism 4 weeks postpartum.

PMID- 9570613
TI  - Asymptomatic profound oxyhemoglobin desaturation following interscalene block in
      a geriatric patient.
AB  - BACKGROUND AND OBJECTIVES: Interscalene block can be chosen for complete
      anesthesia for shoulder surgery. Phrenic nerve block occurs with almost all
      interscalene blocks, but is well tolerated in most patients. This may not be the
      case in selected geriatric patients. METHODS: The patient is a 90-year-old female
      with osteoarthritis of the left shoulder scheduled for total shoulder
      anthroplasty. Past medical history revealed hypertension, mild mitral valve
      insufficiency, and a remote episode of congestive heart failure. She underwent
      interscalene block with 40 mL of 1.4% mepivacaine, 1:200,000 epinephrine freshly
      added, alkalinized with sodium bicarbonate. RESULTS: The onset of the block was
      rapid and complete. The patient had minimal intravenous sedation (0.5 mg
      midazolam) and was resting comfortably with a respiratory rate of 12-14
      breaths/min. Approximately 5 minutes after the injection of local anesthetic, the
      patient was noted to be alert, cyanotic, denying dyspnea, with an oxygen
      saturation of 75-85%. A chest radiograph revealed elevation of the ipsilateral
      hemidiaphragm and no pneumothorax or other pathology. Despite supplemental oxygen
      by face mask, desaturation persisted and general anesthesia was induced. On
      emergence from anesthesia, the patient had a complete interscalene block. Repeat
      chest radiograph after resolution of the block revealed return of hemidiaphragm
      position and no other pathology. The patient was extubated in the recovery room
      without difficulty. Following extubation the patient demonstrated stable
      respirations and normal oxyhemoglobin saturation. CONCLUSIONS: Ipsilateral
      phrenic nerve paralysis caused significant respiratory compromise in an elderly
      patient without known significant pulmonary disease.

PMID- 9570614
TI  - Inguinal paravascular (lumbar plexus) neurolytic block--description of a catheter
      technique: case report.
AB  - BACKGROUND AND OBJECTIVES: We provided care for a 47-year-old female with a
      history of lung carcinoma and bony metastases who sustained a pathologic fracture
      of the right acetabulum causing severe and uncontrolled pain in the right groin.
      Her pain was rated as 8-10 on a 10-point visual analog scale (VAS). Her terminal
      disease and poor surgical risk precluded therapeutic operative intervention.
      Consequently, a neurolytic block of the lumbar plexus was performed as a
      palliative measure. METHODS: A modified inguinal paravascular (lumbar plexus)
      block technique was used. A 17-gauge Tuohy needle was inserted in the groin area
      just lateral to femoral artery and 1 cm below the inguinal ligament. A guide wire
      was threaded through the needle and subsequently an angiogram catheter was
      introduced over the wire into the psoas muscle. Radiographic confirmation of the
      position was obtained, and the catheter was secured in place. A prognostic block
      using an infusion of 0.25% bupivacaine at 5 mL/h was initiated for the first 2
      days. On the third day a neurolytic block with 6% phenol was performed. RESULTS:
      Marked pain relief was experienced by the patient (VAS: 0-1). Sensory block in
      the femoral, lateral femoral cutaneous, and obturator nerve distributions was
      elicited. Motor weakness in the femoral nerve was demonstrated. Narcotic use was
      markedly reduced, and the patient was discharged to home in a pain-free state.
      CONCLUSIONS: This case report supports the feasibility of placing a catheter via
      a modified anterior inguinal paravascular block technique and its subsequent use
      for both local anesthetic infusion and neurolytic block of the lumbar plexus.

PMID- 9570615
TI  - Sympathetic hyperactivity, respiratory failure, pruritus, and anesthesia after
      unintentional epidural injection of potassium chloride: case report.
AB  - BACKGROUND AND OBJECTIVES: A combination of epidural and general anesthesia has
      been widely used to attenuate the surgical stress response and to provide
      postoperative analgesia. This case report illustrates the use of this anesthetic
      technique. Analgesia was induced with local anesthetic in the immediate
      postoperative period using unintentional 19.1% potassium chloride (KCl) as
      diluent. METHODS: An ASA I male patient was scheduled for surgical correction of
      idiopathic megaesophagus under continuous epidural anesthesia combined with
      general anesthesia. In the postoperative period, while preparing 10 mL 0.125%
      bupivacaine to be administered through the epidural catheter for pain control, 5
      mL 19.1% KCl was unintentionally used as diluent, resulting in a 9.55% potassium
      solution concentration. RESULTS: The patient developed warmness of the lower
      limbs, tachycardia, hypertension, intense pruritus on the chest, agitation,
      exacerbation of sensory and motor blocks, and respiratory failure secondary to
      pulmonary edema, requiring ventilatory support. Total recovery was observed after
      24 hours. CONCLUSIONS: Epidurally injected potassium leads to severe clinical
      manifestations caused by autonomic dysfunction, spinal cord irritation, and
      possible release of histamine. Despite continuous recommendations, ampule
      misidentification still happens in hospitals, frequently leading to serious
      accidents.

PMID- 9570616
TI  - Perisciatic injection of steroid for the treatment of sciatica due to piriformis
      syndrome.
AB  - BACKGROUND AND OBJECTIVES: Piriformis syndrome causing sciatica is sometimes
      refractory to conventional treatments including physical therapy, piriformis
      injections, and even caudal epidural steroid injections. Surgical release of the
      piriformis muscle has been described for difficult cases of piriformis syndrome,
      but is occasionally accompanied by morbidity. Another approach to treating
      piriformis syndrome is presented. METHODS: A perisciatic injection of steroid
      using simple landmarks and utilizing a nerve stimulator to locate and inject near
      the sciatic nerve and into the piriformis muscle is described. RESULTS: Six
      patients that did not respond to conventional treatments, but did respond to
      perisciatic steroid injections are presented. CT scan, in one of the patients,
      confirmed correct needle placement when this technique and landmarks were used.
      CONCLUSION: Patients with piriformis syndrome who were refractory to conventional
      treatments but responded to perisciatic injections of steroid are presented.

PMID- 9570617
TI  - In defense of the nerve stimulator.

PMID- 9570618
TI  - Paresthesias during brachial plexus block.

PMID- 9570620
TI  - Spinal introducer with needle stabilizer.

PMID- 9570621
TI  - Cauda equinopathy is not necessarily cauda equina syndrome.

PMID- 9570619
TI  - Intraarticular controversy continues.

PMID- 9570622
TI  - Implications of cartilage invasion in surgically treated laryngeal carcinoma.
AB  - BACKGROUND: Cartilage invasion adversely affects the outcome of laryngeal
      carcinoma treated with radiotherapy. The UICC and American Joint Committee on
      Cancer (AJCC) classify laryngeal carcinoma with cartilage invasion as T4 or stage
      IV. METHODS: This study examines the prognostic significance of cartilage
      involvement in T3,4 N0,1 glottic carcinoma treated with total laryngectomy.
      Patients with tumor extension to pharynx, tongue, and thyroid gland,
      extracapsular spread, positive resection margins, and less than 2 years' follow
      up were excluded. RESULTS: Sixty-seven pT3 (cartilage free of tumor) and 37 pT4
      (cartilage invaded by tumor) cases were studied. The difference between the pT3
      and pT4 groups in terms of local or regional recurrence, distant metastasis, and
      determinate survival was not significant. CONCLUSIONS: The results of this study
      question the use of cartilage invasion as a staging parameter for surgically
      treated laryngeal carcinoma. However, further studies with larger sample sizes
      are required to fully elucidate the prognostic significance, if any, of cartilage
      invasion in surgically treated cancer of the larynx.

PMID- 9570623
TI  - Studies of the anatomy and pathology of the orbit in carcinoma of the maxillary
      sinus and their impact on preservation of the eye in maxillectomy.
AB  - BACKGROUND: The periorbita has been traditionally regarded as the decisive layer
      whose involvement in carcinoma of maxillary sinus indicates orbital exenteration.
      Anatomic texts depict that the orbital fat rests on the periorbita. Our
      experience at surgical dissections has been different. METHODS: Twenty-five
      patients underwent total maxillectomy for advanced (T3-T4) carcinoma of the
      maxillary sinus with postoperative radiotherapy during a 15-year period between
      1981 and 1995. In 11 patients, despite radiologic evidence of orbital invasion,
      and in 5 patients with infiltration of the periorbita, the eye could be preserved
      without evidence of recurrence. In 6 patients who in addition underwent orbital
      exenteration, histopathologic evidence of tumor invasion of the orbit was present
      in only one surgical specimen. RESULTS: Clinicoanatomic studies have clearly
      shown the presence of a thin, distinct fascial layer which surrounds the
      periocular fat and separates it from the periorbita. Neither clinical examination
      nor imaging could predict orbital invasion with absolute accuracy.
      Histopathologic examination of the surgical specimens shows that tumor
      infiltration of the eye is rare. CONCLUSION: Periocular fat is surrounded by a
      thin fascial layer and is not in direct contact with the periorbita.
      Intraoperative decision making with respect to preservation of the eye is
      sometimes essential.

PMID- 9570624
TI  - Verrucous carcinoma of the larynx: a review of 53 patients.
AB  - BACKGROUND: Verrucous carcinoma of the larynx is a rare laryngeal neoplasm that
      can be confused with a benign process. Although usually curable at an early
      stage, it can be locally aggressive if left untreated. We describe our experience
      with this tumor and make recommendations for diagnosis and treatment. METHODS:
      From 1960 through 1990, 53 patients received initial treatment for verrucous
      carcinoma of the larynx at the Mayo Clinic. We retrospectively reviewed the
      presentation, diagnosis, treatment, and outcomes in these patients. All cases
      were confirmed by histologic examination. RESULTS: All but two patients were men,
      and most were smokers. Most tumors were found in the glottis, and 72% were T1
      lesions at presentation. Six patients had hybrid tumors consisting of
      conventional squamous cell carcinoma along with the verrucous component. Sixteen
      patients had lesions that had been diagnosed as benign before they were seen at
      our institution. Treatment ranged from transoral excision to
      laryngopharyngectomy. Ten patients experienced recurrence, but only two patients
      died of the tumor. No pure verrucous lesion metastasized, and overall survival
      was similar to that of an age- and sex-matched cohort from the Western North
      Central U.S. white population. CONCLUSIONS: When discovered early, verrucous
      carcinoma of the larynx can be treated by local excision with good results;
      extensive lesions, however, may require more-aggressive procedures. Close
      communication between the pathologist and the clinician as well as adequate
      biopsy is essential for diagnosis. Patients with a conventional squamous cell
      carcinoma coexistent with a verrucous lesion must be treated as if they had
      invasive squamous cell carcinoma.

PMID- 9570625
TI  - Parotid gland tumors: histologic reevaluation and reclassification of 478 cases.
AB  - BACKGROUND: The histologic classification of epithelial salivary gland tumors may
      present difficulties due to their great morphologic diversity. METHODS: In this
      study, 478 parotid gland tumors were reevaluated and reclassified according to
      the 1991 WHO histologic classification of salivary gland tumors. RESULTS: In 56
      cases, the original diagnosis was changed, either within the benign or the
      malignant tumor group. In six cases (1.3%), the original diagnosis was changed
      from benign to malignant or vice versa. CONCLUSIONS: During the mean follow-up
      period of 10.3 years, no events occurred supporting or rejecting the proposed
      change in diagnosis in these six patients. With regard to the three cases in
      which an original malignant diagnosis was made, the possibility of an
      overdiagnosis, and therefore an overtreatment, remains.

PMID- 9570626
TI  - PET scanning in head and neck oncology: a review.
AB  - BACKGROUND: The objective of this study was to review and describe the usage of
      fluorine-labeled deoxyglucose (FDG) and positron emission tomography (PET) in the
      diagnosis and management of head and neck cancer. METHODS: Several prospective
      series,-including 159 newly diagnosed and previously untreated and 23 previously
      irradiated head and neck squamous cell carcinoma patients initially seen at the
      Wake Forest University Medical Center and evaluated by clinical examination,
      conventional computed tomography/ magnetic resonance imaging (CT/MRI) scans, PET
      scans, and histopathologic studies,-were reviewed and the findings summarized for
      comparison of the correct differentiation of primary and metastatic cancers and
      for postirradiation tumor clearance in a subsegment of those cases. RESULTS:
      Positron emission tomography scanning using a fluorine-labeled deoxyglucose (FDG)
      radiotracer proved as reliable as conventional scanning for primary and
      metastatic tumor identification. Compared with clinical examination, PET was
      better for identification of nodal metastatic tumors but poorer for small primary
      tumors. For previously irradiated patients treated at least 4 months before the
      test, PET scanning was clearly superior to clinical examination and conventional
      imaging in differentiating tumor recurrence from soft-tissue irradiation effects.
      CONCLUSIONS: Fluorine-labeled deoxyglucose-PET scanning is comparable to
      conventional imaging of head and neck cancers in detecting primary and metastatic
      carcinoma. Lack of anatomic detail remains its major drawback. Currently, its
      greatest role is in the evaluation of the postradiotherapy patient.

PMID- 9570627
TI  - Surgical outcomes in head and neck cancer patients 80 years of age and older.
AB  - BACKGROUND: Elderly patients over 80 years of age represent a growing population,
      some of whom have complex medical problems that are compounded by the presence of
      upper aerodigestive tract cancer. METHODS: Forty-three patients, aged 80 years
      and older, who were initially seen with head and neck squamous cell carcinoma
      from 1986 to 1992 at a tertiary-care center were compared with 79 similar
      patients, aged 65 years or younger, in a retrospective, case-control study.
      RESULTS: Median overall survival for the patients over 80 years of age was
      significantly lower than that for the controls (p = .001). However, their overall
      survival was similar to the actuarial survival for the general octogenarian
      population. Advanced age also adversely affected local control (p < .001) and
      disease-specific survival (p = .041). Although the older age group had a higher
      frequency of morbid preoperative conditions, there were no significant
      differences in perioperative or postoperative complications between the two
      groups. CONCLUSIONS: Careful preoperative staging and evaluation of associated
      medical illnesses, as well as skillful perioperative and postoperative
      management, are essential for reducing operative morbidity and mortality in the
      octogenarian patient. Successful outcome depends upon appropriate surgical
      management, treatment of concurrent illnesses, and minimization of postoperative
      complications. Individualized surgical management of the elderly head and neck
      cancer patient is effective, well tolerated, and clinically indicated for upper
      aerodigestive tract malignancies.

PMID- 9570628
TI  - Prognostic significance of c-erbB-2 oncoprotein expression in intestinal-type
      adenocarcinoma of the sinonasal tract.
AB  - BACKGROUND: The c-erbB-2 gene codes for a putative transmembrane protein, similar
      in structure to the epidermal growth factor receptor. Amplification and/or
      overexpression of the gene has been recently described with a prognostic
      significance in a variety of human adenocarcinomas. METHODS: A monoclonal
      antibody against the c-erbB-2 oncoprotein has been used immunocytochemically in a
      retrospective study of formalin-fixed, paraffin-embedded samples from 28
      consecutive intestinal-type adenocarcinomas (ITACs) of the nose and paranasal
      sinuses. RESULTS: Nine out of 28 primary adenocarcinomas (32%) showed positive
      staining. Clinical follow-up data, available for all patients, suggested in a
      univariate analysis a correlation between c-erbB-2 expression and poor prognosis,
      as measured by 5-year disease-free (p = .02) and overall survival curves (p =
      .07) as well as by recurrence of disease and the appearance of regional and
      distant metastases (p = .08). In multivariate analysis, c-erbB-2 expression was
      statistically significant in terms of disease-free survival (p = .046) but not of
      overall survival (p = .091) in our series. CONCLUSIONS: These data indicate that
      c-erbB-2 oncogene activation could be involved in sinonasal tract oncogenesis,
      with possible prognostic implications.

PMID- 9570629
TI  - Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the
      oral cavity and tongue base.
AB  - BACKGROUND: Nuclear deoxyribonucleic acid (DNA) content is a prognostic factor in
      several tumors, and decisions regarding treatment have been made using this
      parameter. Nevertheless, there is no agreement in head and neck cancer. The
      purpose of the present study was to ascertain whether tumor DNA content
      correlated with prognosis in cases of primary squamous cell carcinoma (SCC) of
      the oral cavity and tongue base. METHODS: A retrospective study of formalin
      fixed, paraffin-embedded tissue from patients with histologically confirmed SCC
      of the oral cavity and tongue base was performed using flow cytometry. Tumor DNA
      content was studied in 109 sets of specimens from previously untreated patients.
      All of them underwent surgical resection at the University "Hospital de La
      Princesa" between 1982 and 1992. Clinical parameters (age, sex, site of primary
      tumor, clinical stage, adjuvant therapy received, and disease-free and overall
      survival) and histologic parameters (histopathologic stage, tumor
      differentiation, type of inflammatory infiltration, presence of perineural
      invasion) were recorded in all cases. An exhaustive statistical analysis was
      applied. RESULTS: Only the histograms of 93 patients were adequate for
      consideration. In flow cytometric analysis, DNA aneuploidy was observed in 51
      tumors (55%). The proportion of aneuploid tumors was significantly higher in
      advanced-stage carcinomas (p < .05), tumors with perineural invasion (p < .05)
      and in men (p < .05). In the 24 patients with lymph node metastasis, the
      incidence of aneuploidy was 82% (19 of 24) (p < .05). The rate of metastasis and
      aneuploidy increased as the degree of differentiation decreased (p < .05 for
      both). Patients with aneuploid carcinomas in both early and advanced stages had
      shorter relapse-free and overall survival periods than did the patients with
      diploid tumors (p < .001 for both). A Cox regression analysis demonstrated that
      ploidy was the single most important prognostic factor in determining relapse and
      death (p < .001 for both). CONCLUSIONS: The results indicate that tumor DNA
      analysis by flow cytometry appears to be useful as a supplement to clinical and
      histologic evaluation in predicting the tendency of SCC of the oral cavity and
      tongue base to metastasize to regional lymph nodes and to predict the outcome of
      the disease.

PMID- 9570630
TI  - Current status of pharyngolaryngo-esophagectomy and pharyngogastric anastomosis.
AB  - BACKGROUND: Pharyngolaryngo-esophagectomy and pharyngogastric anastomosis (PLO &
      PGA) is one of the surgical options in the management of tumors arising from the
      hypopharynx and cervical esophagus. Indications of the operation and the outcome
      are changing over the years. To examine these, the experience of this operation
      in one Institute (the Head and Neck Division of the Department of Surgery, The
      University of Hong Kong at Queen Mary Hospital, Hong Kong) over the last 30 years
      was reviewed. METHODS: From 1966 to 1995, a total of 317 patients underwent PLO &
      PGA. The clinical results of 69 patients operated on between 1986 and 1995 were
      analyzed and compared with those of the two groups of patients reported
      previously from the same Institute to establish the current status of PLO & PGA.
      RESULTS: The demographic data of three groups of patients were similar. In
      previous years, 53% of the primary tumors were advanced laryngeal carcinomas
      extending to the hypopharynx, whereas the other 47% originated from
      hypopharyngeal and cervical esophageal regions. In recent years, all patients
      belonged to the latter group. CONCLUSIONS: The hospital mortality has decreased
      from 31% to 9%, and the incidence of morbidity such as anastomotic leakage and
      bleeding has also been reduced, from 20% to 10%. This may be related to the
      introduction of transthoracic endoscopic mobilization of the esophagus and
      patient selection. The overall minor morbidity has, however, remained at about
      49%, and the 5-year actuarial survival rate has improved, from 18% in the 1970s
      to 24.5% at present.

PMID- 9570631
TI  - Cervical lymphadenitis caused by nontuberculous mycobacteria in immunocompetent
      children: clinical and therapeutic experience.
AB  - BACKGROUND: Cervical lymphadenitis is a frequent manifestation of nontuberculous
      mycobacteria (NTM) infection in immunocompetent children. Surgical excision, the
      treatment of choice, is often incomplete and may be difficult. A medical approach
      could reduce treatment morbidity. METHODS: Systemic antibiotic therapy was
      administered to seven children for at least 6 months as treatment for cervical
      lymphadenitis due to NTM: rifabutin and clarithromycin in 4 cases; rifabutin,
      clarithromicyn, and ethambutol in 2 cases; rifabutin, amikacin, and cycloserine
      in 1 case. RESULTS: All patients, six followed for a mean of 3 years and one for
      6 months, were initially seen with regression of local signs of infection without
      relapse. Toxicity, likely due to rifabutin, was represented by neutropenia in
      three patients and yellow skin pigmentation in one patient. CONCLUSIONS: Systemic
      antibiotic therapy was safe and effective in children with lymphadenitis due to
      NTM. This approach could represent a sound alternative or adjunct to surgery.

PMID- 9570632
TI  - Human papillomavirus and head and neck cancer: epidemiology and molecular
      biology.
AB  - BACKGROUND: Human papillomaviruses (HPV) are known to cause cancers of the cervix
      and other anogenital tract sites. Molecular biology has provided some evidence as
      to the specific mechanisms involved in the HPV-related carcinogenesis.
      Epidemiologic and molecular biology studies have also suggested that HPV
      infection may be associated with cancers of the head and neck. METHODS: This
      review summarizes the biology of HPV and its potential etiologic role in head and
      neck cancer. Published reports were used to determine the prevalence of HPV in
      benign, precancerous, and neoplastic lesions of the oral cavity, pharynx, and
      larynx. The prevalence was also examined by head and neck site, HPV type, and
      method of HPV detection. In addition, the occurrence of HPV in normal head and
      neck tissue, epidemiologic factors related to HPV infection, and clinical
      implications are discussed. RESULTS: Overall, the frequency of HPV in benign and
      precancerous lesions ranged from 18.5% to 35.9%, depending upon the detection
      methodology. Based upon the most sensitive method of detection, polymerase chain
      reaction (PCR), the overall prevalence of HPV in head and neck tumors was 34.5%
      (416 of 1205 tumors). The majority of HPV-positive tumors contained the "high
      risk" HPV types 16 (40.0%) and 18 (11.9%). Among head and neck sites, HPV was
      most often detected in tumors of the oral cavity (59%), followed by the pharynx
      (43%), and larynx (33%). The frequency of HPV positivity in oral samples from
      healthy individuals ranged from 1% to 60%. A limited number of descriptive and
      analytic epidemiologic studies have indicated that age (<60 years) and sex (male)
      were associated with the presence of HPV in the tumor, whereas tobacco and
      alcohol use were not. The relationship between HPV and survival is unclear, with
      few comprehensive studies currently available. CONCLUSIONS: The prevalence of
      HPV, particularly the high-risk types, suggests a potential etiologic role for
      the virus in head and neck cancer. Molecular biology has provided important data
      on the interaction of the HPV oncoproteins with genes important in cell cycle
      control. Nonetheless, more basic research is needed to describe the physical
      state of the virus in a variety of cell types and the interaction with other
      genes. In addition, epidemiologic research is required to further understand the
      association between HPV and demographic and other risk factors as well as
      possible routes of transmission. Finally, much work is warranted to provide a
      definitive assessment of the prognostic significance of HPV in head and neck
      cancer.

PMID- 9570633
TI  - The difficult airway: cardiopulmonary bypass--the ultimate solution.
AB  - BACKGROUND: Large, compressive thyroid masses are usually removed as an elective
      procedure. Rarely is a patient's condition allowed to progress to severe
      respiratory distress before surgical intervention is recommended. When allowed to
      progress, management of the airway can be problematic. METHODS: A case report of
      a patient with a neglected thyroid lymphoma is presented. RESULTS: The natural
      progression of the disease, leading to impending airway collapse, necessitated
      emergency management of the airway. Due to supraglottic edema and a large neck
      mass, traditional methods of securing the airway were not feasible. Initiation of
      femoral-femoral cardiopulmonary bypass, under local anesthesia, ensured adequate
      oxygenation and allowed a controlled tracheotomy to be performed. CONCLUSIONS:
      The result obtained suggests that this approach provides a safe solution for
      airway control when intubation or a surgically created airway is either
      unsuccessful or too hazardous.

PMID- 9570634
TI  - Adjuvant immunotherapy for patients with melanoma.

PMID- 9570636
TI  - Post-ischemic alterations in [3H]FK506 binding in the gerbil and rat brains.
AB  - We investigated post-ischemic changes in FK506 binding protein (FKBP) in the
      brain after transient global ischemia in gerbils or transient focal ischemia in
      rats. [3H]FK506 was used to label FKBP as a immunophilin. In transient global
      ischemia, [3H]FK506 binding showed a transient reduction in the frontal cortex
      only 1 h after recirculation. In the striatum, the dorsolateral part exhibited a
      significant increase in [3H]FK506 binding 5, 24 and 48 h after ischemia. However,
      the ventromedial part showed a transient elevation in [3H]FK506 binding 24 h
      after ischemia. Thereafter, the ventromedial part showed no conspicuous change in
      [3H]FK506 binding up to 7 days after ischemia. The dorsolateral part also showed
      no significant change in [3H]FK506 binding 7 days after ischemia. In the
      hippocampus and thalamus, [3H]FK506 binding was unchanged in the stratum radiatum
      of the hippocampal CA1 sector, hippocampal CA3 sector, dentate gyrus and thalamus
      up to 7 days after ischemia. However, the stratum oriens of the hippocampal CA1
      sector showed a significant reduction in [3H]FK506 binding 48 h and 7 days after
      ischemia. A histological study showed that transient cerebral ischemia caused a
      severe damage in the striatum and hippocampal CA1 sector. In a model of transient
      focal ischemia, a marked increase in [3H]FK506 binding was also found in the
      striatum and cerebral cortex where severe infarctions were observed. These
      results demonstrate that post-ischemic change in [3H]FK506 binding between the
      striatum and hippocampus may be produced by different mechanisms. Furthermore,
      our findings suggest that immunophilins may play some role in the pathogenesis of
      ischemic diseases.

PMID- 9570635
TI  - Role of proinflammatory cytokines in cerebral ischemia: a review.

PMID- 9570637
TI  - Thiamine pyrophosphate-dependent and thiamine metabolizing enzymes in the
      deafferented cerebellum and in the intact cerebral cortex of rat.
AB  - The effects of chemical (CD) and surgical (SD) deafferentation of the cerebellum
      on thiamine pyrophosphate (ThPP)- dependent enzymes (transketolase, TK; pyruvate
      , PDH, and alpha-ketoglutarate, alphaKGDH, dehydrogenases) and thiamine (Th)
      metabolizing enzymes (thiamine pyrophosphokinase, ThPK; thiamine mono-, ThMPase,
      and pyrophosphatases, ThPPase) were evaluated in vitro in rats in steady state
      conditions. The enzymes were also determined in the intact cerebral cortex of the
      same animals. CD was carried out by i.p. injection of 3-acetylpyridine, followed
      by harmaline and niacinamide. SD was carried out by complete dissection of the
      peduncles of the left cerebellar hemisphere. Chemical and surgical cerebellar
      deafferentations significantly lowered the contents of both Th-metabolizing and
      ThPP-dependent enzymes in the cerebellum without modifying those of the cerebral
      cortex. ThPK and TK, which are particularly concentrated in neurons, were the
      most affected enzymes. The decrease in ThPP-dependent enzymes shown here is
      associated with the slowing down of the Th phosphorylation-dephosphorylation
      cycle and with no modification in the ThPP content in the cerebellum, both of
      which were found in a previous study. Cerebellar deafferentation seems to only
      affect the apoenzyme moiety of the enzymes.

PMID- 9570638
TI  - Nitroarginine, an inhibitor of nitric oxide synthase, prevents changes in
      superoxide radical and antioxidant enzymes induced by ammonia intoxication.
AB  - Injection of large doses of ammonium salts leads to the rapid death of animals.
      However, the molecular mechanisms involved in ammonia toxicity remain to be
      clarified. We reported that injecting ammonium acetate (7 mmol/kg) to rats
      increases the production of superoxide and reduces the activities of some
      antioxidant enzymes in rat liver and brain. We proposed that these effects
      induced by ammonia intoxication would be mediated by formation of nitric oxide.
      To test this possibility we tested whether injection of nitroarginine, an
      inhibitor of nitric oxide synthase, prevents the effects of ammonia intoxication
      on antioxidant enzymes and superoxide formation. Following injection of ammonia,
      glutathione peroxidase, superoxide dismutase and catalase activities were
      decreased in liver by 42%, 54% and 44%, respectively. In brain these activities
      were reduced by 35%, 46% and 65%, respectively. Glutathione reductase remained
      unchanged. Superoxide production in submitochondrial particles from liver and
      brain was increased by more than 100% in both tissues. Both reduction of activity
      of antioxidant enzymes and increased superoxide radical production were prevented
      by previous injection of 45 mg/kg of nitroarginine, indicating that ammonia
      induces increased formation of nitric oxide, which in turn reduces the activity
      of antioxidant enzymes, leading to increased formation of superoxide.

PMID- 9570639
TI  - Plasma thiamine deficiency associated with Alzheimer's disease but not
      Parkinson's disease.
AB  - In this study we compared plasma and erythrocyte thiamine levels in a group of
      patients with idiopathic Parkinson's Disease (iPD) to a group of patients with
      probable Alzheimer's Disease (pAD). pAD patients had significantly lower plasma
      thiamine levels (raw and z-score) than iPD patients. A significantly higher
      number of pAD patients had plasma thiamine deficiencies than iPD patients. The
      demographics of our patient groups were similar to those reported by other
      investigators, making age, sex and nutritional status unlikely explanations for
      our findings. These results suggest that plasma thiamine deficiency is associated
      with pAD but not with iPD.

PMID- 9570640
TI  - Erp72 expression activated by transient cerebral ischemia or disturbance of
      neuronal endoplasmic reticulum calcium stores.
AB  - Stress-induced activation of the expression of the endoplasmic reticulum (ER)
      resident chaperon and member of the protein disulfide isomerase family erp72 was
      studied after transient cerebral ischemia in vivo using the four-vessel occlusion
      method and experimental depletion of ER calcium stores in primary neuronal cell
      cultures. After 8 days in vitro, neurons were exposed to thapsigargin (Tg), an
      irreversible inhibitor of ER Ca2+-ATPase, or the Tg solvent DMSO. In separate
      experiments neurons were pre-loaded with the cell-permeant calcium chelator BAPTA
      AM before Tg exposure. Stress-induced changes in erp72 expression were analysed
      by quantitative PCR. Transient cerebral ischemia produced a significant increase
      in erp72 mRNA levels which rose to about 200% of control (hippocampus) or 300% of
      control (cortex). After depletion of ER calcium stores neuronal erp72 mRNA levels
      rose markedly, peaking at 12 h of recovery. Counteracting the Tg-induced rise in
      cytoplasmic calcium activity by preloading cells with the chelator BAPTA-AM did
      not influence erp72 expression significantly, suggesting that the activation of
      erp72 expression resulted from the depletion of ER calcium stores and not from
      the corresponding increase in cytoplasmic calcium activity. An activation of
      erp72 expression is indicative of a disturbance of ER function. The results of
      the present study therefore provide evidence to support the notion that transient
      cerebral ischemia induces disturbances of neuronal ER function, probably through
      a depletion of ER calcium stores.

PMID- 9570641
TI  - Portacaval anastomosis results in more widespread alterations of cerebral
      metabolism in old versus young adult rats: implications for post-shunt
      encephalopathy.
AB  - Treatment of portal hypertension by portal decompressive surgery or transjugular
      intrahepatic portosystemic stent shunt (TIPS) results in new or worsening
      episodes of portal-systemic encephalopathy, particularly in older patients. As
      part of a series of studies to elucidate the pathophysiologic mechanisms
      responsible for the age-related increased portal-systemic encephalopathy
      following shunt surgery, local cerebral glucose utilization, a measure of
      regional brain functional activity, was assessed using the 14C-2-deoxyglucose
      autoradiographic technique in 2 month-old (young adult) and 24 month-old (old
      adult) rats following end-to-side portacaval anastomosis. Cerebral glucose
      utilization was decreased by 22% (p<0.05) in frontal cortex of 2 month-old rats
      following portacaval anastomosis. More widespread alterations of glucose
      utilization, involving frontal and frontoparietal cortices, as well as thalamic
      structures were observed in the brains of 24 month-old rats following portacaval
      anastomosis despite blood ammonia concentrations of a comparable magnitude.
      Decreased cerebral glucose utilization in frontal and frontoparietal cortex of
      old adult rats following portacaval anastomosis probably results from decreased
      cerebral energy requirements as a consequence of neurotransmitter-related
      dysfunction. The greater susceptibility of aging brain to the deleterious effects
      of portacaval anastomosis is consistent with the higher incidence of
      encephalopathy in older cirrhotic patients following portacaval anastomosis or
      TIPS.

PMID- 9570642
TI  - Antimicrobial therapy for bacterial endocarditis on native valves.

PMID- 9570643
TI  - Spread of Neisseria meningitidis group A clone III-I meningitis epidemic into
      Zambia.
AB  - The epidemic of Neisseria meningitidis group A clone III-I strain began with the
      1987 outbreak in Mecca, Saudi Arabia. Intense epidemics in African countries
      occurred the following year. Clone III-I was first isolated from Africa in 1988
      in Chad, followed by epidemics in Ethiopia (1989), Kenya and Tanzania (1989), and
      The Central African Republic (1992). We report an epidemic of Neisseria
      meningitidis group A clone III-I afflicting Zambia during a 2-year period (April
      1992-May 1994). This extension of the 'meningitis belt' southwards into Central
      Africa is cause for concern. Active surveillance for this disease should be
      carried out by all African countries, even those outside the well described sub
      Saharan 'meningitis belt'.

PMID- 9570644
TI  - Effect of faecal consistency on virological diagnosis.
AB  - A study was set up to investigate the effect of consistency of routine faecal
      specimens on the diagnostic yield by electron microscopy (EM) and virus
      isolation. A total of 3078 specimens were characterized as solid, semisolid, or
      liquid. Of 2568 specimens processed by EM a virus was demonstrated in 8.6% of
      liquid, 19.9% of semisolid and 25.2% of solid specimens (Chi-squared for linear
      trend, P value <0.0001). This observation was valid for both adenovirus (2.4%,
      5.0% and 6.6%) and rotavirus (5.2%, 13.6% and 16.6%). Virus isolation was
      positive in 3.6% of liquid, 17.4% of semisolid and 18.1% of solid specimens. (Chi
      squared for linear trend, P value <0.0001). We suggest that solid faecal
      specimens at the end of an episode of diarrhoea will have a higher diagnostic
      yield than liquid specimens at the peak of symptoms. Our findings repudiate the
      commonly held dogma that viruses of gastroenteritis are more likely to be found
      in liquid than in solid faecal specimens. This finding has important implications
      for those establishing diagnostic algorithms for the investigation of viral
      gastroenteritis.

PMID- 9570645
TI  - Central nervous system and ophthalmic involvement in nephropathia epidemica
      (European type of haemorrhagic fever with renal syndrome).
AB  - Central nervous system (CNS) - related symptoms occur in haemorrhagic fever with
      renal syndrome (HFRS). To study the CNS and ophthalmic involvement in
      nephropathia epidemica (NE), the European type of HFRS, we included 26 patients
      in a prospective study. Most common CNS-related symptoms were headache (96%),
      insomnia (83%), vertigo (79%), nausea (79%), and vomiting (71%). Ophthalmic
      symptoms were reported by 82% of patients; 41% had photophobia and 50% had
      impaired vision. A transient loss of vision was recorded in one patient, who also
      had a generalized seizure. Minor white matter lesions were found in about half of
      the patients investigated with brain magnetic resonance imaging (MRI).
      Electroencephalography (EEG) showed severe alterations in only one patient, and
      slight and reversible patterns in another two patients. Neopterin, interleukin-6
      and interferon-gamma levels in the cerebrospinal fluid (CSF) were elevated, which
      may indicate immune activation. However, we found no evidence of intrathecal NE
      virus replication. We conclude that CNS-related symptoms are common in NE, and
      transient ophthalmic involvement can be demonstrated in about half of the
      patients.

PMID- 9570646
TI  - Childhood bacterial meningitis in Saudi Arabia.
AB  - This study analysed the bacterial aetiology and outcome of childhood meningitis
      observed over an 11-year period. Charts of 70 children with this diagnosis were
      reviewed. Three children were under 1 month of age, five were between 1 and 3
      months and 60 were between 3 months and 5 years. The remaining two were over 5
      years. There were 36 females and 34 males. The presenting symptoms in decreasing
      order of frequency were fever 86%, vomiting 29%, poor feeding 19%, seizure 14%
      and lethargy 14%. Aetiological organisms were as follows: Haemophilus influenzae
      66%, Streptococcus pneumoniae 24%, Neisseria meningitidis 4%, Group B
      Streptococci 4%, and Staphylococcus aureus 2%. All H. influenzae isolates except
      one were sensitive to ampicillin. None of the S. pneumoniae isolates were
      resistant to penicillin. Complications occurred in 26% of the patients and
      included subdural effusion 23%, hearing loss 14%, seizure disorder 10%,
      developmental delay 9%, hydrocephalus 6% and motor deficit 30%. One patient died.
      Among H. influenzae cases, one of the 15 patients treated with steroids developed
      hearing loss. In contrast, four out of 31 who did not receive steroid therapy
      suffered from hearing loss. Haemophilus influenzae type b is the predominant
      cause of childhood bacterial meningitis in Saudi Arabia. Universal H. influenzae
      type b vaccination for children is highly recommended.

PMID- 9570647
TI  - The rapid diagnosis and clinical features of human herpesvirus 6.
AB  - Since human herpesvirus 6 (HHV6) was first linked with exanthem subitum in 1988
      there has been increasing evidence that the morbidity associated with acute HHV6
      infection may be more significant and variable. However, the clinical
      appreciation of HHV6 infection has been hampered by the lack of rapid and
      clinically useful diagnostic methods. In this prospective study of hospitalized
      febrile children under 3 years of age we compared three rapid viral diagnostic
      methods, (polymerase chain reaction assay (PCR), IgM serology and direct antigen
      detection), with conventional serology on paired serum samples. In addition, we
      documented the range of clinical features associated with acute HHV6 infection.
      Of 67 children recruited, 11 (16%) had evidence of acute HHV6 infection: six had
      detectable, specific, IgM; four were PCR positive; and one was PCR positive with
      IgM. Direct antigen testing on batched frozen samples detected no infections.
      Apart from high fever (median peak 38.5 degrees C), common features were non
      specific. Two children had febrile convulsions and only one child had a non
      specific rash. We conclude that rapid microbiological diagnosis at present
      requires two tests (IgM and PCR). HHV6 is a common cause of febrile illness in
      hospitalized infants with no rash and should be considered in their diagnosis.

PMID- 9570648
TI  - Diffuse necrotic hepatic lesions due to visceral leishmaniasis in AIDS.
AB  - A rare case of an AIDS patient who developed scattered necrotic involvement of
      the liver caused by Leishmania infantum is described. Of interest, marked
      splenomegaly, hypergammaglobulinemia and serum anti-Leishmania antibodies were
      absent and an incomplete response to therapy was observed. Diagnosis of visceral
      leishmaniasis (VL) was achieved by the demonstration of numerous amastigotes in
      both hepatocytes and macrophages on liver biopsy. Hepatic necrotic lesions, which
      when extensive could lead to acute hepatic failure, possibly reflect an atypical
      manifestation of liver involvement caused by L. infantum and depend on the
      immunological impairment which characterizes AIDS patients, thus preventing the
      formation of granulomas. Our observation confirms that VL can manifest atypical
      aspects in HIV-positive patients depending on the degree of the immunodeficiency.
      The frequency and severity of this pathology accounts for the need to list VL
      among AIDS-defining conditions.

PMID- 9570649
TI  - The lack of therapeutic effect of Saccharomyces boulardii in the prevention of
      antibiotic-related diarrhoea in elderly patients.
AB  - Diarrhoea is a common side effect of antibiotic therapy, especially in the
      elderly. Saccharomyces boulardii is a non-pathogenic yeast which has been
      demonstrated to reduce the frequency of diarrhoea in patients due to a variety of
      causes. We set out to assess its role in preventing antibiotic-related diarrhoea.
      Consecutive patients over the age of 65 admitted to medical wards, and who were
      being prescribed antibiotics, were randomized to receive either S. boulardii 113
      g twice daily or placebo for as long as they received antibiotics. Bowel habit
      was monitored using a record of interdefaecatory intervals (IDI) and stool form
      graded 1-4 (hard to liquid). Stool samples were tested every fourth day for
      Clostridium difficile toxin. Of the 72 patients randomized, 69 completed the
      study. There was no difference in sex, age, duration of antibiotic use, length of
      hospital stay, IDI, stool form, the proportion of patients receiving laxatives,
      the number of patients experiencing watery stools (seven vs. five), or the
      presence of C. difficile toxin (five vs. three). No side effects were
      attributable to S. boulardii. There was no evidence that the concomitant use of
      S. boulardii with antibiotics alters patients' bowel habits or prevents the
      appearance of C. difficile toxin in the stool. Thus, S. boulardii cannot be
      recommended as a 'natural' way to prevent antibiotic-related diarrhoea. This
      highlights the need for proper evaluation of probiotics before their unrestricted
      use in medical practice.

PMID- 9570650
TI  - The use of pulsed-field gel electrophoresis for subdivision of Salmonella
      typhimurium in an outbreak situation.
AB  - An institutional outbreak of gastroenteritis provided an opportunity to
      investigate further the isolates of Salmonella typhimurium by pulsed-field gel
      electrophoresis (PFGE). Three phage types were identified. Antibiograms
      identified two types and two distinct patterns were found on PFGE. If phage
      typing alone is used for epidemiological study of strains, it is possible that an
      association between strains may be missed.

PMID- 9570652
TI  - Current use of the TORCH screen in the diagnosis of congenital infection.
AB  - The aim of the study was to determine the number of congenital infections
      detected in Dublin with the current use of the TORCH screen. A review of all
      laboratory results was undertaken with subsequent review of relevant medical
      charts. A total of nine cases were documented in a 5-year period from January
      1991 to December 1995. Six of these had already been suspected. There was a
      failure to follow up 47% of positive screens. TORCH screening in Ireland has an
      unacceptably low yield, and in the opinion of the authors should be abolished.

PMID- 9570651
TI  - Serum hepatitis G virus (HGV) RNA in multitransfused thalassemics from eastern
      Sicily.
AB  - The prevalence of hepatitis G in a multitransfused population was studied. HGV
      did not appear to be a major contributor to liver pathology in this group and the
      prevalence was surprisingly low.

PMID- 9570653
TI  - Epidemiological study of latent and recent infection by Toxoplasma gondii in
      pregnant women from a regional population in the U.K.
AB  - AIMS: To determine the prevalence of IgG and IgM to Toxoplasma gondii (TG) and
      predict the incidence of infection during pregnancy and in foetuses. METHODS:
      Thirteen thousand pregnant women from eastern England were tested at the time of
      booking for antenatal screening. Screening was carried out for the presence of
      IgG and IgM anti-TG, followed by confirmation with commercially available assays.
      RESULTS: Latent infection to TG was found in 7.7% of women and increased with age
      from 6.8 to 17.8%. Recent infection accounted for an additional 0.4% equally
      distributed across age groups. No difference was found between urban and rural
      place of residence. A 1-2% incidence of TG infection every 5 years of age was
      found. IgM-only cases were mostly false positives and were unsuitable for
      statistical analysis. On the basis of both IgM and IgG imputed data, TG infection
      was found significantly higher during the first trimester of pregnancy. Three to
      sixteen TG-infected foetuses per 10000 pregnancies were predicted. CONCLUSIONS:
      The east of England has a low prevalence of TG infection and therefore a high, at
      risk population of pregnant women. Repeated screening during pregnancy would be
      expensive, but would detect and possibly prevent infection in approximately 10
      neonates per 10000 women.

PMID- 9570654
TI  - Evaluation of a Brucella enzyme immunoassay test (ELISA) in comparison with
      bacteriological culture and agglutination.
AB  - An ELISA test for IgG and IgM antibrucella antibodies was found to be effective
      in diagnosis of human brucellosis. Assays for IgG and IgM in 30 culture-positive
      cases gave significant ELISA values. By the standard agglutination test, 10% of
      these cases gave readings less than 1:160. These are considered insignificant,
      taking 1:160 as the accepted cut-off value. Moreover, in an extra 135 samples
      from suspected brucella cases, where only serology was requested (77.6% of all
      cases), 7.4% were found to have IgM brucella antibodies by ELISA. In all of
      these, the corresponding agglutination titres were less than 1:80 and hence
      reported as insignificant. We report the detection of IgG and IgM antibodies in
      samples from patients with both acute and chronic disease. In few patients with
      acute disease, only IgM was detected. These findings are discussed in comparison
      with earlier studies. Finally, the ELISA test, in addition to measuring antibody
      classes directly, also detects incomplete antibodies. By this, it can efficiently
      replace the 2 mercaptoethanol test (2ME) and the Coomb's antihuman-globulin test.
      This saves considerable laboratory cost and time.

PMID- 9570655
TI  - Candidaemia in an Australian teaching hospital: relationship to central line and
      TPN use.
AB  - We performed a retrospective review of patient case records to identify risk
      factors for candidaemia and to assess incidence, management and outcome of
      candidaemia in an Australian teaching hospital. Between January 1994 and June
      1996, 38 cases of candidaemia were identified. The incidence was 0.74 per 1000
      admissions of 24 h duration, and 1.54 per 1000 admissions of 5 days or more. The
      mortality rate was 34%, with eight of 13 (62%) of these deaths attributable to
      candidaemia. Risk factors included underlying gastrointestinal disease (66%) and
      recent abdominal surgery (61%), while recent broad spectrum antibiotic use was a
      contributing factor in 95%. Twenty-nine patients (76%) had a vascular access
      device in situ at time of detection. This was the apparent source of candidaemia
      in 28 (97%). Twenty-six (90%) were being used for TPN administration. Of patients
      receiving TPN, 5.2% developed candidaemia. Standard central venous catheters
      (CVC) were present in 21 patients (55%), having been in situ for an average of
      12.7 days. Eighteen (86%) had been in situ for 7 days or more. Management
      involved removal of any implicated intravascular device. Thirty of 33 early
      survivors received antifungal chemotherapy. Therapy with amphotericin B,
      fluconazole alone or amphotericin B followed by fluconazole was equally
      effective. Concurrent corticosteroid use and neutropaenia contributed to
      increased mortality. Candidaemia is not benign. Policies regarding regular
      changing of central lines, especially in the setting of TPN administration and
      control of broad spectrum antibiotic use are appropriate measures aimed to reduce
      incidence. Management involves removal of implicated lines and antifungal
      chemotherapy. Pre-emptive therapy for candida infection should be considered in
      selected patients with the likelihood of TPN-related central line sepsis.
      Fluconazole is an effective alternative to amphotericin B in non-neutropenic
      patients.

PMID- 9570656
TI  - Acute Herpes zoster in Tayside: demographic and treatment details in
      immunocompetent patients 1989-1992.
AB  - Medical records of 105 patients admitted to Tayside hospitals with acute Herpes
      zoster without underlying immunosuppression were examined retrospectively for the
      period 1984-1992. In this elderly population (median age: 79 years) there was a
      female preponderance (70.5%), most admissions were for trigeminal zoster (49.5%)
      and length of stay ranged from 1-70 days (median: 11 days), indicating
      significant morbidity. There was a wide variation in both pre-admission and
      inpatient treatment; 53.3% of patients did not receive any anti-viral therapy
      prior to admission, and prescribing patterns for in-patients revealed marked
      differences, according to the dermatome affected. Idoxuridine 5% solution was
      prescribed by 15.24% of General Practitioners. Given the significant morbidity
      and associated costs of Herpes zoster, and that existing anti-viral agents exert
      maximal benefit when administered early in the course of the disease,
      recommendations are made with respect to appropriate therapy, and auditing
      current management of this serious illness, which is expected to increase in
      prevalence as the population ages.

PMID- 9570657
TI  - Bilateral deafness due to congenital CMV and not rubella reinfection.
AB  - We report on an infant with bilateral deafness discovered at the age of 5 months
      caused by a retrospectively diagnosed primary maternal CMV infection after
      definitive exclusion of maternal rubella reinfection as a cause of fetal
      infection.

PMID- 9570658
TI  - Visceral leishmaniasis (Kala-azar) in two patients with HIV-1 infection: atypical
      features and response to therapy.
AB  - Visceral leishmaniasis (VL) is a well recognized opportunistic infection in
      patients with HIV-1 infection, which may occasionally present with atypical
      features. We describe two patients with advanced HIV-1 infection (CD4<100/ mm3)
      in whom visceral leishmaniasis presented with atypical features, and their
      response to therapy. Atypical features of visceral leishmaniasis in the two
      infected patients include absence of fever, dissemination to the duodenal mucosa
      and to the skin as xanthoma-like lesions. Therapy and secondary prophylaxis
      remain unsatisfactory, and studies to evaluate combinations of amphotericin B and
      immunotherapy are needed.

PMID- 9570659
TI  - Cryptococcosis: an unusual opportunistic infection complicating B cell
      lymphoproliferative disorders.
AB  - We report two cases of cryptococcosis in patients with Waldenstrom's
      macroglobulinaemia and chronic lymphocytic leukaemia that responded to prolonged
      therapy with systemic amphotericin and flucytosine. Cryptococcosis, although more
      common in those with impaired cell mediated immunity, should also be considered
      as a complication in patients with impaired antibody responses.

PMID- 9570660
TI  - Enterocytozoon bieneusi multiorgan microsporidiosis in a HIV-infected patient.
AB  - Multiorgan microsporidiosis due to Enterocytozoon bieneusi was diagnosed in an
      HIV-infected patient. The parasite was found and identified as E. bieneusi by
      transmission electron microscopy in stools, duodenal biopsy, nasal discharge and
      sputum. No clinical improvement or parasite eradication was obtained after
      albendazole therapy, but the patient remained alive 9 months after diagnosis.

PMID- 9570661
TI  - Epstein-Barr (EB) monoarthritis leading to ruptured Baker's cyst.
AB  - We report a case of Epstein-Barr (EB) infection that presented as an acute
      monoarthritis of the knee. This formed a Baker's cyst which ruptured into the
      gastrocnemius. The peripheral and synovial white blood counts were dominated by
      neutrophils. After repeated aspirations, spontaneous resolution occurred.

PMID- 9570662
TI  - Failure of intravenous ribavirin in the treatment of invasive adenovirus
      infection following allogeneic bone marrow transplantation: a case report.
AB  - We report a case of fatal adenovirus infection in a 37-year-old female who
      underwent allogeneic bone marrow transplantation (BMT) for acute myelogenous
      leukaemia (AML). Post BMT she developed acute grade II graft-vs.-host disease
      (aGVHD) requiring high-dose steroids and anti-thymocyte globulin. Additionally,
      her clinical course was complicated with adenovirus-associated haemorrhagic
      cystitis and viraemia. Intravenous ribavirin was obtained and administered for 5
      days without success; the patient's mental status deteriorated rapidly and she
      died on day 69 post-transplant. Radiological imaging revealed diffuse cortical
      necrosis. At autopsy adenovirus was identified in her bladder, kidneys and lungs.

PMID- 9570663
TI  - Acute exacerbation of vasculitis during interferon-alpha therapy for hepatitis C
      associated cryoglobulinaemia.
AB  - A significant, previously unreported, adverse reaction to interferon-alpha
      therapy is reported. Immediately after the commencement of low dose therapy a man
      with hepatitis-C associated cryoglobulinaemia developed a purpuric rash and a
      severe, reversible impairment of renal function. This observation may elucidate
      the immunopathogenesis of vasculitis.

PMID- 9570664
TI  - Meningitis due to a combined infection with Cryptococcus neoformans and
      Streptococcus pneumoniae in an AIDS patient.
AB  - We report on a case of dual infection with Cryptococcus neoformans and
      Streptococcus pneumoniae in the cerebrospinal fluid of a patient with AIDS. To
      our knowledge this represents the first case to be reported in the English
      literature. In immunocompromised patients the importance of performing both the
      Gram- and India-ink stain and cryptococcal antigen test on CSF specimens with
      completely normal biochemical and cellular parameters is emphasized.

PMID- 9570665
TI  - Genital recurrent infection occurring 6 months after meningitis due to the same
      herpes simplex virus type 2 (HSV-2) strain evidence by restriction endonuclease
      analysis.
AB  - Herpes simplex virus type 2 (HSV-2) is more often sexually transmitted and
      associated with genital recurrent infection. However, HSV-2 neurological
      manifestations such as meningitis were already reported. We describe a case of
      meningitis due to HSV-2, preceded by signs suggesting a common cystitis, in a
      woman with no history of primary or recurrent genital infection. Six months later
      genital herpetic lesions occurred. One HSV-2 strain was obtained from
      cerebrospinal fluid (CSF) and another from genital lesions. The molecular
      comparative analysis using restriction endonuclease digestion patterns showed the
      similarity of the two strains. Our report illustrates that HSV-2 infections are
      underdiagnosed and that molecular techniques can be of value in clarifying the
      physiopathology of HSV diseases.

PMID- 9570666
TI  - Massive hepatosplenomegaly, jaundice and pancytopenia in miliary tuberculosis.
AB  - A 29-year-old Caucasian woman presented to hospital with a 2-day history of
      diarrhoea, anorexia and rigors. Investigations showed abnormal liver function
      tests, hyponatremia, hypoalbuminaemia and lymphopenia. The initial chest
      radiograph was normal. A bone marrow trephine biopsy showed non-caseating
      granulomata and she subsequently developed miliary shadowing on the chest
      radiograph. A transjugular liver biopsy confirmed the presence of acid-alcohol
      fast bacilli. Despite starting triple therapy for miliary tuberculosis she
      remained febrile and developed massive hepatosplenomegaly, jaundice and
      pancytopenia. Standard triple therapy was substituted with ethambutol,
      streptomycin and oral prednisolone and the patient made a dramatic recovery. The
      clinical symptoms of miliary tuberculosis are frequently non-specific and the
      onset of the illness is often insidious. The liver is involved in almost all
      patients with miliary tuberculosis, but massive hepatosplenomegaly and jaundice
      are rare. Standard triple-therapy should be discontinued when there is
      significant liver dysfunction, and corticosteroids should be considered for
      patients with miliary tuberculosis who fail to respond to conventional therapy.

PMID- 9570667
TI  - High influenza morbidity and mortality in unvaccinated elderly people in Curacao.

PMID- 9570668
TI  - Primary peritonitis due to Lactobacillus fermentum.

PMID- 9570669
TI  - Detection of HTLV-II proviral sequences in HIV-immunosuppressed patients with
      HTLV indeterminate serological patterns.

PMID- 9570670
TI  - Chlamydia trachomatis and bronchiolitis.

PMID- 9570671
TI  - Chlamydia pneumoniae in the female genital tract.

PMID- 9570672
TI  - Lack of activity of an association of detergent and germicidal agents on the
      infectivity of Cryptosporidium parvum oocysts.

PMID- 9570673
TI  - A case of urinary tract infection caused by Bacillus cereus.

PMID- 9570674
TI  - Gestational parvovirus infection in United Arab Emirates.

PMID- 9570675
TI  - Selection and transplantation of autologous hematopoietic CD34+ cells for
      patients with multiple myeloma.
AB  - Here we review our recent experience addressing the issue of positive selection
      and transplantation of hematopoietic CD34+ cells to reduce neoplastic
      contamination in peripheral blood (PB) autografts from patients with multiple
      myeloma (MM). We evaluated PB samples from 30 pretreated MM patients following
      the administration of high dose cyclophosphamide (Cy; 7g/m2 or 4g/m2) and
      granulocyte-colony stimulating factor (G-CSF), for collection of circulating stem
      cells (PBSC) to support hematopoietic reconstitution following myeloablative
      radio-chemotherapy. Twenty six patients showed adequate mobilization of CD34+
      progenitor cells and were submitted to PBSC collection. Circulating hematopoietic
      CD34+ cells were highly enriched by avidin-biotin immunoabsorption,
      cryopreserved, and used to reconstitute BM function after myeloablative therapy
      in 13 patients. The median purity of the enriched CD34+ cell population was 89.5%
      (range 51-94%) with a 75-fold increase compared to the pretreatment samples. The
      median overall recovery of CD34+ cells and CFU-GM was 58% (range 33-95%) and 45%
      (range 7-100%), respectively. Positive selection of CD34+ cells resulted in 2.5-3
      log of plasma cells and CD19+ B-lineage cells depletion as determined by
      immunofluorescence studies, although DNA analysis of CDR III region of IgH gene
      demonstrated the persistence of minimal residual disease (MRD) in 5 out of 6
      patient samples studied. Myeloma patients were reinfused with enriched CD34+
      cells after myeloablative therapy consisting of total body irradiation (TBI, 1000
      cGy) and high dose Melphalan (140 mg/m2) or Melphalan (200 mg/m2) alone. They
      received a median of 5 x 10(6) CD34+ cells/kg and showed a rapid reconstitution
      of hematopoiesis: the median time to 0.5 x 10(9) neutrophils, 20 and 50 x 10(9)
      platelets/L of PB was 10, 11 and 12 days, respectively. When we analyzed the
      immunological reconstitution of this group of patients, we observed a rapid and
      full recovery of total lymphocyte and NK cell count, although the absolute CD4+
      cell count was lower than pretreatment level. These results, as well as other
      clinically significant parameters, did not significantly differ from those of
      patients (=13) receiving unmanipulated PBSC following the same pretransplant
      conditioning regimen. The results of this trial demonstrate that positive
      selection of CD34+ cells reduces the contamination of myeloma cells from the
      apheresis products up to 3 log and provides a cell suspension capable of
      restoring a normal hematopoiesis after a TBI-containing conditioning regimen.
      Based on this pilot trial, we have recently started a clinical study involving a
      double autotransplant, conditioned with melphalan (200 mg/m2) followed by
      melphalan (140 mg/m2) and busulphan (14 mg/kg), supported by the reinfusion of
      highly purified CD34+ cells.

PMID- 9570676
TI  - Clinical use of hematopoietic growth factors in the myelodysplastic syndromes.
AB  - Recent advances in the molecular genetics of myelodysplastic syndromes (MDS) have
      shed new light on the pathogenesis of MDS allowing a better understanding of the
      defects of differentiation of the transformed clone and suppression of normal
      hematopoiesis. The clinical hematologist, however, continues to be challenged
      with the treatment of patients with MDS. Pancytopenia and defective function of
      neutrophils and platelets lead to a high risk of infectious and hemorrhagic
      complications. The progression to acute myeloid leukemia adds to morbidity and
      mortality. Supportive care including red blood cell and platelet transfusions are
      still the cornerstone of therapeutic management. While prophylactic
      administration of G-CSF or GM-CSF cannot be recommended, treatment of febrile
      neutropenia might benefit from administration of G-CSF in addition to
      antibiotics. Administration of high-dose erythropoietin will improve
      erythropoiesis in around 20% of the patients, mainly in those with rather
      preserved erythroid function and no or low transfusion need. Coadministration of
      erythropoietin with either G-CSF or GM-CSF could increase the response rate.
      Allogeneic stem cell transplantation still is the only curative treatment and
      prolongs survival. Intensive chemotherapy for advanced MDS is possible with an
      acceptably low rate of early death and a complete remission rate between 45% to
      60%, while initial results of autologous transplantation are promising.

PMID- 9570677
TI  - Natural and therapy-induced anti-GM-CSF and anti-G-CSF antibodies in human serum.
AB  - Serum samples were obtained from patients with lymphoid and plasma cell
      malignancies who received after chemotherapy human recombinant GM-CSF or G-CSF.
      Sera from some patients revealed the presence of anti-cytokine antibodies,
      particularly after repetitive cytokine injections. Antibody Fab binding in a
      saturable manner by ELISA and Western immuno-blotting confirmed antibody
      specificity. Anti-cytokine antibodies were detected before the exogenous cytokine
      injections in some patients, but increasing antibody levels were found after one
      or subsequent treatments. Low levels of anti-GM-CSF and anti-G-CSF antibodies
      were also detected in a relatively large proportion (about 10-30%) of normal sera
      from different adult healthy volunteers who had never been treated before with
      exologous cytokines as well as from cord blood. EBV-immortalized cord blood
      derived B-cell cultures were also found to produce anti GM-CSF and/or anti-G-CSF
      antibodies with high frequency.

PMID- 9570678
TI  - Growth factors in the therapy of myelodysplasia: biological aspects.
AB  - Growth factors (GF) are reported to play an important role in the therapy of
      myelodisplastic syndromes (MDS). After in vitro administration a consistent group
      of MDS may respond to GF but the possibility of differentiation, regulation or
      expansion of myelodisplastic clones following GF therapy is still a question to
      be answered as their optimum dose and combinations. To validate if in vivo
      treatment with GF, may promote the regulation or the recovery of myelopoiesis
      and/or modify the clonality of the responses, we gave G-CSF after intensive
      chemotherapy in high risk MDS and acute leukemia evolving from MDS patients.
      According to our data the use of G-CSF after intensive chemotherapy may improve
      the CR rate without increase of leukemic transformation. However the answer were
      clonal and the remission duration remained very short so we suggest to utilize
      this time to perform other therapeutic strategies such as, when possible, the
      BMT.

PMID- 9570679
TI  - Hairy cell leukemia and allied chronic lymphoid leukemias: current knowledge and
      new therapeutic options.
AB  - This review deals mainly with the essentials of hairy cell leukemia (HCL)
      detailing clinical aspects, laboratory findings and morphology. Rare
      manifestations of HCL are listed. Newer aspects relating to cytokines, soluble
      interleukin receptors and TNF are reviewed. Differential diagnosis including HCL
      variant, SLVL, PLL and CLL/PLL are discussed. Prognostic factors and in
      particular therapeutic aspects are detailed with particular emphasis on the new
      purine analogues Pentostatin and 2-CdA. A list of suggested reading is offered.

PMID- 9570680
TI  - Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24
      patients.
AB  - To explore the feasibility and potential advantages of PBSC in allogeneic
      transplantation, we grafted 24 patients (age 16-57, median 37) with different
      hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA =
      1), 23 HLA-identical to their siblings and 1 partially matched. Cells were
      collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5
      days, and stored at 4 degrees C until infusion. The patients were conditioned
      with chemotherapy regimens including busulfan and cyclophosphamide in the
      majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The
      graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x
      10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2
      to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on
      (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day
      13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU
      GM number in the inoculum and time to hematologic reconstitution. Acute GVHD
      (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18
      evaluable (55%) patients. We found no relationship between occurrence of acute or
      chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7
      died after transplantation. Fifteen patients are currently alive and disease-free
      67 to 710 (median 286) days from the graft. Allogeneic transplantation with
      unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence
      and severity seems comparable to that of bone marrow transplantation, but there
      may be an increase in chronic GVHD, mainly of the extensive form.

PMID- 9570681
TI  - High-dose therapy in acute leukemia.
AB  - The use of intensive induction chemotherapy, primarily with combinations of an
      anthracycline and cytarabine, allows complete remission rates of greater than 70%
      in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia
      (ALL). However, with currently available standard-dose therapy, only 20% of young
      adults are cured. In order to substantially increase the cure rate, adequate post
      remission therapeutic strategies are mandatory. Three different therapeutic
      options are currently available: (i) dose-intensified chemotherapy; (ii)
      allogeneic stem cell transplantation; (iii) autologous stem cell transplantation.
      These therapeutic options should be carefully evaluated according to prognostic
      information, including cytogenetic and molecular abnormalities as well as
      phenotypic characterization. Randomized trials of intensive postremission therapy
      have now confirmed improved leukemia-free survival with the use of allogeneic or
      autologous transplantation. Autologous transplantation appears to be the most
      promising treatment modality in AML. Improved preparative regimens and purging
      techniques may be critical factors in determining the effectiveness of autologous
      transplantation in AML patients. In adult ALL, the role and optimal methods of
      stem cell transplantation are still under investigation.

PMID- 9570682
TI  - Immunohistochemistry of bone-marrow biopsy.
AB  - In a percentage of cases, conventional morphologic evaluation of bone-marrow
      needle biopsy (BMNB) in insufficient to achieve a firm diagnosis. Under these
      circumstances, immunohistochemistry plays a basic role, providing an easy and
      objective key for the interpretation of the pattern observed in most instances.
      Herein, the authors focus on the technical procedures, which allow extensive
      application of immunohistochemistry to the study of BMNB, as well as on the
      panels of antibodies needed for the identification of the most relevant
      conditions.

PMID- 9570683
TI  - Molecular techniques in hematopathology.
AB  - Molecular techniques have already earned a place in the management of hematologic
      disorders. The requests of clinical hematologists to Pathology include, besides
      the diagnosis, any additional information useful for prognosis and therapeutic
      choices, as well as expertise and technologies to follow-up patients. To fulfill
      these commitments, pathologists have been resorting to classical morphology,
      cytochemistry, immunocytochemistry, and have only recently come to include
      molecular genetic techniques. Most of the molecular methods of practical utility
      are based on the analysis of DNA. The DNA methodologies of routine applicability
      mainly include Southern blotting and polymerase chain reaction (PCR). Southern
      blotting recognizes major DNA rearrangements, whereas PCR-based methods allow to
      recognize both gross chromosomal modifications and fine gene alterations,
      including point mutations. PCR techniques may also be used for partially degraded
      DNA from formalin-fixed paraffin-embedded tissues. Here we will draw a brief
      overview of the role of molecular genetic techniques in the pathology practice
      for the diagnosis, prognosis and follow-up of neoplastic diseases, using examples
      from our experience.

PMID- 9570684
TI  - Mobilization/transplantation of peripheral blood progenitor cells for aggressive
      non-Hodgkin's lymphoma with marrow involvement.
AB  - Thirty-five aggressive non-Hodgkin's lymphomas (NHL) with marrow involvement
      received high-dose cyclophosphamide (7 g/m2) and G-CSF in order to collect
      peripheral blood progenitor cells (PBPC). Fourteen patients were in partial
      remission, 16 patients were in relapse ("sensitive", 12; "resistant", 4) and 5
      patients were in refractory to conventional treatment. A good yield of PBPC was
      obtained in 30 patients, while a low number of CD34+ cells and of CFU-GM was seen
      in two cases. Two patients entered progression and one patient died. Thirty
      patients underwent PBPC autografting. Twenty-nine out of 35 (83%) patients
      entered complete remission (CR). Two patients died in CR of infection following
      marrow aplasia 3 and 6 months after autografting. At 3 years the probability of
      survival and disease-free survival (DFS) are of 62% and 51% respectively.

PMID- 9570685
TI  - The role of idarubicin in adult acute lymphoblastic leukaemia: from drug
      resistance studies to clinical application.
AB  - Idarubicin (4-demethoxydaunorubicin) is more potent and less cardiotoxic than
      daunorubicin or doxorubicin. These properties suggested a role in acute
      myelogenous leukaemia, that was confirmed by prospective randomized trials. In
      acute lymphoblastic leukaemia of adults, on the contrary, there is very little
      information regarding idarubicin. We have used idarubicin since 1991 and found,
      in a retrospective comparison with a doxorubicin regimen, a decreased incidence
      of primarily refractory disease. The role of idarubicin in the postremission
      phase could not be assessed in detail but an early intensive use of
      anthracyclines, either idarubicin or doxorubicin, was associated with an improved
      outcome in early-B CD10+ and t(9;22)/BCR-leukaemias. Concurrent in vitro studies
      demonstrated that idarubicin, at pharmacologically relevant concentrations, was
      less sensitive to P-glycoprotein-mediated drug efflux than daunorubicin and was a
      more effective agent to use with cyclosporin-A to circumvent this drug resistance
      mechanism. Idarubicin is a very effective drug for the early management of adult
      acute lymphoblastic leukaemia and may be presently considered (along with
      cyclosporin-A or other modulator) as the reference anthracycline for cases
      overexpressing the P-glycoprotein drug resistance mechanism.

PMID- 9570686
TI  - Soluble molecules as biological markers in Hodgkin's disease.
AB  - Hodgkin's disease (HD) is characterised by a complex architectural and functional
      derangement of involved tissues. The interactions between neoplastic cells and
      the heterogeneous microenvironment lead to the expression and release of
      different cellular messengers [cytokines, soluble (s) forms of cytokine receptors
      and other membrane-associated molecules] which can be detected in the circulation
      and evaluated as biological markers. We and others investigated several of these
      molecules looking for their possible role as diagnostic or prognostic parameters
      in patients with HD. We update here the results of serum determination of sIL
      2Ralpha, sCD8, sICAM-1, sTNFRs, and sCD30 in a large series of cases from our
      institution. We found that their levels are generally increased at presentation
      and during the active phase of the disease. They correlate with stage and
      clinical aggressiveness and have some prognostic implication. However, we were
      unable to demonstrate a prognostic usefulness for their detection, with the
      exception for sCD30 which was found to directly correlate with disease spread and
      burden at presentation and, most importantly, to have an independent prognostic
      significance. The prognostic significance of sCD30 might derive from a crucial
      involvement of this molecule in the pathophysiology of HD.

PMID- 9570687
TI  - Molecular pathways in low grade B-cell lymphoma.
AB  - Low grade B-cell non-Hodgkin's lymphomas (B-NHL) represent a markedly
      heterogeneous group of lymphoproliferative disorders, including B-cell chronic
      lymphocytic leukemia/small lymphocytic lymphoma (B-CCL/SLL), lymphoplasmacytoid
      lymphoma (LPL), follicular lymphoma (FL), mucosa-associated lymphoid tissue
      lymphoma (MALTL), and splenic lymphoma with villous lymphocytes (SLVL). The
      molecular pathogenesis of low grade B-NHL is characterized by distinct genetic
      pathways which selectively associate with each clinicopathologic category. At
      diagnosis, B-CLL/SLL frequently display deletions of 13q14 and trisomy 12,
      whereas evolution to Richter's syndrome associates with disruption of p53. LPL
      carries t(9;14)(p13;q32) in 40-50% of the cases, leading to the deregulated
      expression of the PAX-5 gene. FL consistently harbors rearrangements of BCL-2
      independent of the cytologic variant. With time, a fraction of FL cases
      accumulates mutations of p53 and evolves into a high grade B-NHL. Low grade MALTL
      are characterized by the frequent occurrence of trisomy 3 and, occasionally, by
      p53 mutations. SLVL carries p53 mutations in a fraction of cases. The
      identification of distinct genetic categories among low grade B-NHL may help in
      the therapeutic stratification of these disorders. In addition, genetic lesions
      of low grade B-NHL have proved to be a useful molecular marker for monitoring
      minimal residual disease.

PMID- 9570688
TI  - Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.
AB  - The peculiar clinical, histomorphological and biological characteristics of PMBCL
      are reviewed. Special emphasis is given to the frequent aggressive clinical
      behaviour of this lymphoma in which conventional prognostic factors seem
      inadequate to identify high risk cases. The need for new clinical and/or
      biological prognostic markers is stressed.

PMID- 9570689
TI  - Gestational administration of cadmium alters the neurotransmitter levels in
      newborn rat brains.
AB  - The effects of gestational and early lactational intoxication by cadmium (Cd)
      were studied in the brain of young Wistar rats. Pregnant rats were exposed to 10
      mg of cadmium acetate per litre of drinking water, from initiation of pregnancy
      to parturition or until postnatal day 5. At birth or on postnatal day (PND) 5 the
      pups were weighed, sacrificed and brains were removed and frozen for later study.
      Protein, lipid and nucleic acid contents were measured and the brain Cd
      concentration was determined. Levels of dopamine (DA), 5-hydroxytryptamine (5-HT)
      and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5
      hydroxyindoleacetic acid (5-HIAA) were measured in neonatal pup brain by higher
      performance liquid chromatography with electrochemical detection. The results
      from this experiment showed that Cd increased the 5-HT and 5-HIAA contents in all
      areas of the brain and the DA and DOPAC levels in mesencephalon, but decreased
      the DA and DOPAC levels in the metencephalon. On the other hand, Cd intoxication
      did not modify the other biochemical parameters measured, with the exception of a
      decrease in nucleic acids on PND 5.

PMID- 9570690
TI  - Ultrastructural changes in limb distal nerves of rats with alcoholism and/or
      malnutrition before and after dietary correction.
AB  - To study peripheral nerves changes in chronic alcoholism and in malnutrition, we
      examined ultrastructurally the distal nerve branches of the digits of rats
      treated with four different dietary schemes, as follows: controls (n = 22), fed
      standard rodent diet plus water ad libitum; alcoholism (n = 12), fed the standard
      diet and 2-12% ethanol in drinking water; malnutrition (n = 21), fed with corn
      tortillas instead of standard diet; and alcoholism and malnutrition combined (n =
      22). After 10 months under these conditions, a proportion of animals from each
      group were sacrificed. The remaining rats of the malnutrition and alcoholism
      alone groups were deferred a standard diet. The combined alcohol + malnutrition
      group was subdivided into standard diet, malnutrition and ethanol. After a
      further 4 months under these new conditions, the animals were sacrificed.
      Ultrastructural examination of limb distal nerve branches showed that glycogen
      like particles were more common in malnourished animals, whereas remyelinating
      axons were more numerous in ethanol-treated rats. Bands of regeneration were
      present in both groups, but were more common in animals treated with ethanol.
      These features decreased significantly when the respective nutritional factor was
      reversed. The results confirm that ethanol plays a definitive role in the
      development of alcoholic neuropathy and that malnutrition accentuates, the
      histopathological abnormalities.

PMID- 9570691
TI  - Comparative nephrotoxicity of some antitumour-active platinum and ruthenium
      complexes in rats.
AB  - The nephrotoxicity of three platinum (CPL, KP734, KP735) and three ruthenium
      coordination complexes (KP418, KP692, KP1019) was tested in rats in comparison to
      cisplatin (CP). Renal functional changes (excretion of water, protein, p
      aminohippurate (PAH) and osmolytes) were not observed after the administration of
      10% of the LD450 of the compounds given twice a week for up to 5 weeks. After a
      relatively high single dose of the substances (50% of the LD50), signs of
      nephrotoxicity on the day of maximal renal damage decreased in the following
      order: CP, KP418, CPL, KP734, KP735, KP692 and KP1019. In comparison to CP,
      proteinuria was significantly lower after the administration of any of the
      compounds, especially KP692 and KP1019. Neither renal lipid peroxidation (TBARS)
      nor glutathion status (GSH, GSSG) was affected. In summary, KP735 in the group of
      platinum complexes and KP1019 in the ruthenium group had the lowest
      nephrotoxicity. Other investigators have shown that all complexes induced anti
      neoplastic activity under analogous experimental conditions.

PMID- 9570692
TI  - Thermic transition and glycolytic capacity as critical events in the survival of
      rat liver slices after overnight cold hypoxic preservation.
AB  - Cellular survival and hypoxia-reoxygenation injury in overnight cold-preserved
      liver slices (+/-20 h at 4 degrees C) were investigated. Increased cell death
      after overnight cold hypoxia depended more on temperature than on the
      reoxygenation process itself. Fructose (at 50 mM) added before the onset of
      hypoxia improved survival at the end of 20 h of cold hypoxia over Krebs- or
      glucose-treated slices. Such a protective effect by fructose was also seen during
      the normothermic (37 degrees C) reoxygenation of previously cold hypoxic
      preserved slices, but only in the absence and not in the presence of tert-butyl
      hydroperoxide, a model compound widely used to induce an oxidative stress. The
      protection by fructose was equivalent to that observed when liver slices were
      incubated in the University of Wisconsin solution (UW). Finally, the
      morphological study of haematoxylin and eosin (H & E)-stained slices has shown
      cytoplasmic vacuoles during the reoxygenation step, which were more pronounced in
      UW-treated than in fructose-treated slices.

PMID- 9570693
TI  - Toxicological studies on the leaves of Avicennia marina (mangrove) in rats.
AB  - Haematological, biochemical and pathological effects in rats produced by the salt
      tolerant plant Avicennia marina given at oral doses of 1 or 4 g kg(-1) for three
      consecutive days or 0.5 g kg(-1) day(-1) for 28 consecutive days are reported. No
      overt behavioral changes, moribundity or mortality were seen in either of the two
      experiments. A dose of 1 g kg(-1) did not affect significantly either body or
      liver weights. However, at a dose of 4 g kg(-1) the extract reduced both body and
      liver weights. The extract at both doses significantly increased leucocyte
      (mainly neutrophil) counts but did not affect significantly erythrocyte counts,
      haemoglobin concentration or the haematocrit. Except for a slight, but
      statistically significant, decrease in plasma glucose concentration and an
      increase in Na, Ca, Cu, Mg and cholesterol concentrations and aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) activities, the extract
      exerted no significant effects on plasma biochemistry. The treatment produced
      dose-related mild cellular degeneration in the liver and congestion in the
      central veins. There were also prominent Kupffer's cells and monocellular
      infiltrations. In the kidneys there was shrinkage and cellular degeneration of
      glomeruli and patches of medullary haemorrhage. In the spleen a slight activation
      of the germinal centre in the white pulp was noted. Subchronic treatment with the
      extract did not affect significantly the body and liver weights, the water
      intake, faecal and urinary output, leucocyte and erythrocyte counts, haemoglobin
      or haematocrit. There was a significant decrease in the number of platelets and
      an increase in the number of neutrophils. No significant changes in plasma
      biochemistry were observed, except for a 15% increase in AST activity. Subchronic
      treatment produced a significant reduction in glutathione concentration,
      amounting to about 20%. Histopathological findings after the subchronic treatment
      were similar in nature but milder than those seen after the acute treatment.

PMID- 9570694
TI  - Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from
      peptic ulcer patients.
AB  - Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene and p
      aminobenzoic acid were determined in the bacterium Helicobacter pylori collected
      from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without
      specific concentrations of rhein co-treatment showed different percentages of 2
      aminofluorene and p-aminobenzoic acid acetylation. The data indicate that there
      was decreased NAT activity associated with increased levels of rhein in H. pylori
      cytosols. Inhibition of growth studies from H. pylori demonstrated that rhein
      elicited dose-dependent bacteriostatic activity in H. pylori cultures: i.e. the
      greater the concentration of rhein, the greater the inhibition of growth to H.
      pylori. For the cytosol and intact bacteria examination, the apparent values of
      Km and Vmax were decreased after co-treatment with 40 microM rhein. This report
      is the first demonstration of rhein inhibition of arylamine N-acetyltransferase
      activity and rhein inhibition of growth in the bacterium H. pylori.

PMID- 9570695
TI  - Is triiodothyronine capable of ameliorating pyrethroid-induced thyroid
      dysfunction and lipid peroxidation?
AB  - A study on the effect of triiodothyronine (T3) in the regulation of pyrethroid
      (fenvalerate)-induced thyroid dysfunction and lipid peroxidation was carried out
      in male mice. Fenvalerate (120 mg kg(-1) body wt. daily for 15 days)
      administration led to a decrease in the serum concentration of thyroid hormones
      and the activity of hepatic type I iodothyronine 5'-monodeiodinase (5'D-I) and an
      increase in the level of lipid peroxidation. The decrease in the activity of
      hepatic 5'D-I due to the administration of fenvalerate was restored with the
      administration of T3 (7 microg kg[-1] body wt. on alternate days). The increased
      level of lipid peroxidation was also ameliorated by T3. However, T3 could not
      restore the serum concentration of thyroxine (T4), only that of T3. We suggest
      that the ameliorating role of T3 in the fenvalerate-intoxicated mice could be the
      result of the lipogenic action of the thyroid hormone, which in turn led to the
      restoration of 5'D-I activity.

PMID- 9570696
TI  - Investigations on the in vitro and in vivo genotoxic potential of 5-vinyl-2
      norbornene.
AB  - 5-Vinyl-2-norbornene (VNB: CAS no. 3048-64-4), an industrial chemical that
      produces hyaline droplet nephropathy in the male rat with associated alpha2u
      globulin increases, was investigated in vitro and in vivo for its genotoxic
      potential. A Salmonella typhimurium reverse mutation assay (strains TA98, 100,
      1535, 1537, 1538) was negative both without (dose range 0.003-0.3 mg per plate)
      and with (0.003-0.3 mg per plate) metabolic activation. A forward gene mutation
      test in Chinese Hamster Ovary (CHO) cells (HGPRT locus) did not show any
      significant concentration-related increases in mutation frequencies in the
      absence (0.01-0.1 mg ml[-1]) or presence (0.005-0.1 mg ml[-1]) of metabolic
      activation. In a sister chromatid exchange (SCE) test, VNB did not produce
      statistically significant or dose-related increases in the incidence of SCEs in
      the absence (0.02-0.06 mg ml[-1]) or presence (0.005-0.03 mg ml[-1]) of metabolic
      activation. A bone marrow chromosome aberration test was conducted in groups of
      10 male and 10 female Sprague-Dawley rats exposed for 6 hr/day for 5 consecutive
      days to mean (+/- SD) VNB vapor concentrations of 0 (air control), 48.1 +/- 1.29,
      146 +/- 9.2, or 336 +/- 8.5 ppm. Marrow was collected 6 and 24 hr after the final
      exposure. No statistically significant or dose-related increases in chromosomal
      aberrations occurred in the VNB-exposed animals. 5-Vinyl-2-norbornene did not
      show any potential for genotoxic activity with this in vitro-in vivo battery of
      tests.

PMID- 9570697
TI  - Effects of S-adenosyl-L-methionine and interferon-alpha2b on liver damage induced
      by bile duct ligation in rats.
AB  - Interferon-alpha2b (IFN) is known to prevent and to reverse experimental liver
      fibrosis and damage. S-Adenosyl-L-methionine (SAM) is a well-known
      hepatoprotective substance. The aim of the present work was to determine the
      effect of the administration of both drugs simultaneously to bile duct-ligated
      rats. Administration of IFN (50000 IU s.c.) and/or SAM (10 mg kg[-1] i.m.) began
      15 days after biliary obstruction and continued for a further 15 days. The liver
      was used for glycogen and collagen quantification. Bilirubins and enzyme
      activities were measured in serum. Either SAM or IFN ameliorated all markers of
      liver damage studied. However, when administered together their beneficial
      effects were markedly reduced. It is not possible to explain the antagonistic
      effect of these compounds on liver damage with the present data. More studies are
      needed to determine SAM-IFN interactions.

PMID- 9570698
TI  - Quantitative morphometric analysis of pulmonary deposition of aerosol particles
      inhaled via intratracheal nebulization, intratracheal instillation or nose-only
      inhalation in rats.
AB  - The effectiveness of three techniques to deliver a diazo dye suspension into the
      lungs of rats was compared. The intratracheal nebulization (ITN) technique
      delivered 10 microl of the suspension per 5-ml puff of air in 10 puffs as an
      aerosol. The intratracheal fast instillation (ITFI) technique delivered 100
      microl of the suspension in a single 2-ml puff of air as droplets. The nose-only
      inhalation (NI) technique aerosolized the suspension at an analytical
      concentration that provided a calculated dose equivalent to 100 microl of the
      suspension in a 2-h inhalation period. Immediately after dosing, all the rats
      were killed by exsanguination. The trachea was tied and the lung was inflated in
      situ with air. After fixation, 5-microm thick slices were prepared from each lobe
      of the lung at a plane perpendicular to the axis of the lobar bronchus at levels
      proximal, medial and distal to the hilus. The numbers of bronchi, bronchioli and
      alveolar ducts within four ranges of diameters and the proportion of each
      selected area of lung tissue with and without dye particles were quantified using
      electronic imaging analyzers. The results indicated that ITN and ITFI dispersed
      the particles evenly throughout most of the airways and in patches in the
      alveoli. The NI technique dispersed the particles homogeneously throughout the
      airways and the alveoli in the lungs. The mean number-percentage and the mean
      area-percentage data revealed that the doses delivered by ITN and NI were
      approximately 60% and 10%, respectively, of the ITFI dose. Thus, the ITFI
      technique appeared to be most suitable for pulmonary absorption and disposition
      studies where dosage precision is of primary concern. The ITN technique would
      need further improvement to meet the requirements for dose precision and particle
      distribution. For both ITFI and ITN, particle size was apparently not a critical
      determinant for deposition. The NI technique is suitable for inhalation toxicity
      studies where the pattern and uniformity of particle deposition is the primary
      concern.

PMID- 9570699
TI  - 2,3,6-triaminopyridine, a metabolite of the urinary tract analgesic
      phenazopyridine, causes muscle necrosis and renal damage in rats.
AB  - Some aromatic polyamines form very stable free radicals and readily undergo
      autoxidation with concomitant formation of 'active oxygen' species. These
      substances cause necrosis of striated muscle in rats, and it has been suggested
      that this is due to free radical formation and disruption of energy production
      through their oxidation via the cytochrome c/cytochrome oxidase system of
      mitochondria. 2,3,6-Triaminopyridine, which is structurally related to the
      myotoxic amines and likewise undergoes autoxidation and disrupts mitochondrial
      metabolism, is a metabolite of the widely used urinary analgesic phenazopyridine.
      When administered to rats, triaminopyridine caused extensive necrosis of skeletal
      muscle and a lesser degree of damage to heart muscle. It also induced vacuolation
      and necrosis of distal tubules of the kidney, associated with tubular dilatation
      and cast formation. Both muscle damage and renal tubular necrosis have been
      reported following use or abuse of phenazopyridine, and it is likely that
      triaminopyridine is responsible for both of these effects.

PMID- 9570700
TI  - Acute chest syndrome and sickle cell disease.
AB  - Acute chest syndrome (ACS) is the presence of a new pulmonary infiltrate in
      combination with fever or respiratory symptoms in a patient with sickle cell
      disease. ACS is the leading cause of death in sickle cell disease, and many
      patients suffer from multiple, severe episodes. Age has a striking effect on the
      clinical course and outcome of ACS, with children having milder disease that
      often is infectious. Adults often have severe disease, and pulmonary fat embolism
      is frequently a component of severe ACS. Rapid diagnosis and appropriate therapy
      including antibiotics for atypical infections, fluids, aerosolized beta agonists,
      and adequate pain control are necessary to reduce morbidity. Transfusion is
      indicated in hypoxic patients and can be used to prevent recurrent episodes. As
      the pathophysiology of ACS is further delineated, new treatment strategies will
      be investigated.

PMID- 9570701
TI  - Molecular insights into blood groups and implications for blood transfusion.
AB  - In recent years technologic advances have led to the understanding of the
      molecular genetics of many blood group antigens. This review highlights the
      molecular basis of selected antigens and describes implications for transfusion
      medicine. The knowledge can be used in the following clinical settings to
      genotype a patient: 1) to identify a fetus at risk for hemolytic disease of the
      newborn 2) to genotype patients who have been recently transfused or whose
      erythrocytes have a positive direct antiglobulin test 3) to determine which
      phenotypically Fy(b-) patients have the FY*B gene, 4) to genotype when an antigen
      has a depressed expression on erythrocytes, 5) to mass screen for anitgen
      negative donors, 6) to resolve blood group A, B, and D typing discrepancies, 7)
      to determine the zygosity of RhD, 8) to determine the origin of engrafted
      leukocytes in a stem cell recipient, 9) to determine the origin of lymphocytes in
      a patient with graft-versus-disease, 10) for tissue typing, 11) for paternity
      testing, and 12) for forensic testing.

PMID- 9570702
TI  - How and when to use erythropoietin.
AB  - Recombinant human erythropoietin is used in clinical practice mainly for
      treatment of anemia of renal failure. In the past years, however, its use has
      been approved for other indications, including prevention of anemia in surgical
      patients or in patients undergoing platinum-based chemotherapy, treatment of
      anemia of prematurity, of anemia induced by zidovudine therapy in HIV-infected
      patients, and of anemia induced by chemotherapy of nonmyeloid malignancies.
      Erythropoietin should routinely be given subcutaneously to maximize its effects.
      Most patients undergoing rHuEpo treatment develop functional iron deficiency, a
      situation in which iron supply to the erythroid marrow is inadequate for the
      erythrocyte precursor demand. Iron supplementation should, therefore, be given to
      all individuals receiving rHuEpo except for those patients with increased serum
      iron and transferrin saturation. Outside the setting of uremia, only a portion of
      patients can clearly benefit from erythropoietin therapy; therefore, the use of
      rHuEpo should be individualized in nonrenal applications.

PMID- 9570703
TI  - Current concepts and issues in Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia, although rare, has been the focus of much attention with
      respect to both its clinical features and the characterization of the in vitro
      erythroid defect. Despite this, its pathophysiology is still unclear, and the
      treatment of steroid-refractory patients is still unsatisfactory. The recent
      chromosomal localization of a gene for familial Diamond-Blackfan anemia
      represents an important step forward toward the elucidation of this disorder.
      Therapeutic advances will depend on the development of collaborative studies,
      employing consensus criteria for diagnosis and response to therapy.

PMID- 9570704
TI  - Function of p55 and its nonerythroid homologues.
AB  - The human erythrocyte membrane has served as a model for elucidating novel
      protein-protein and protein-membrane interactions that have broad implications in
      many nonerythroid cells. A detailed analysis of erythrocyte membrane polypeptides
      that migrate in the region of band 4.9 led to the cloning and characterization of
      p55 phosphoprotein. Subsequent studies established that the p55 protein is an
      obligate component of the protein 4.1-glycophorin C complex, which regulates the
      stability and mechanical properties of the erythrocyte plasma membrane. p55 is a
      member of a growing family of signaling and cytoskeletal proteins termed membrane
      associated guanylate kinase homologues (MAGUKs). MAGUKs are multidomain proteins
      consisting of either a single or three copies of the PDZ (PSD-95/Discs large/ZO
      1) domain, an SH3 motif, and a guanylate kinaselike domain. Recent studies have
      implicated MAGUKs in the clustering of ion channels, organization of cytoskeletal
      elements, cell signaling events, and regulation of cell proliferation and tumor
      suppression pathways. The purpose of this review is to summarize recent
      developments concerning the characterization of two human MAGUKs, erythrocyte
      p55, and lymphocyte hDIg.

PMID- 9570705
TI  - Phospholipid asymmetry in health and disease.
AB  - The asymmetric distribution of membrane phospholipids was first described more
      than two decades ago. The selective localization across the bilayer indicated
      that asymmetric biomembranes are assembled and maintained by specific mechanisms
      that control transbilayer lipid sidedness. The loss of phospholipid asymmetry and
      in particular the appearance of phosphatidylserine (PS) on the outer surface is
      associated with many physiologic and pathologic phenomena. Understanding the
      mechanisms that govern membrane lipid sidedness, including those that promote a
      collapse of phospholipid asymmetry, seems essential to understanding the disease
      states in which this unwanted PS exposure, or lack of PS exposure, is observed.
      Recent studies have identified some of the keyplayers in these regulatory
      systems. Their role, as well as the consequences of PS exposure in blood cell
      pathology are summarized in this chapter.

PMID- 9570706
TI  - Malaria and the erythrocyte.
AB  - In terms of global health, the most important disease involving human
      erythrocytes is infection by protozoan parasites of the genus Plasmodium,
      particularly Plasmodium falciparum. Our understanding of the complex processes of
      erythrocyte invasion, remodeling, and cytoadherence has advanced considerably
      over the past few years. Considerable advances have been made in identifying the
      players in each of these phenomena, although identification of the exact
      functional roles for many molecules is still missing. The cloning of the parasite
      adhesin, the development of a transfection system, and a series of new imaging
      and cell biology assays are recent achievements that promise to further our
      understanding not only of the pathogenesis of malaria, but also the functioning
      of erythrocytes.

PMID- 9570708
TI  - Erythroid-specific transcription.
AB  - Over the past year, the range of research related to erythroid cell-specific
      transcription has expanded beyond isolation of its transcriptional players to
      studies that address more complex yet still fundamental questions: first, whether
      these factors form part of a larger protein-protein structure; second, how factor
      interactions with DNA affect the surrounding chromatin configuration; third, how
      this affects the mechanism of gene switching within the beta-like globin cluster;
      and finally, how these regulators are themselves transcriptionally controlled.

PMID- 9570707
TI  - Mechanisms of developmental regulation in globin loci.
AB  - Recent advances in the study of globin gene switching in the context of the
      complete locus have contributed greatly to our understanding of the mechanisms of
      developmental regulation. It has become clear that the interactions between the
      distant locus control region and the individual globin genes, as well as the
      trans-acting factors and physical parameters that affect these interactions, are
      crucial determinants in the developmental modulation of globin gene expression.
      This review concentrates on recent advances in the highly studied human beta
      globin locus and will compare and contrast data from the human alpha-globin locus
      as well as the alpha and beta loci from other species where appropriate.

PMID- 9570709
TI  - Potential therapeutic approaches for the treatment of vaso-occlusion in sickle
      cell disease.
AB  - Vaso-occlusion is the major cause of morbidity and mortality in sickle cell
      disease. The pathogenesis of vaso-occlusion likely involves many complex steps
      related to both the primary event of deoxyhemoglobin S polymerization and the
      many resultant pathologic changes in both the sickle erythrocyte and the vascular
      endothelium. Several therapeutic approaches have been designed to reduce the
      extent of deoxyhemoglobin S polymerization. Although direct chemical inhibition
      of deoxyhemoglobin S polymerization has proven difficult, strategies to increase
      levels of fetal hemoglobin or reverse sickle erythrocyte dehydration have been
      more successful. Although gene therapy is actively being pursued, the ability to
      cure sickle cell disease is currently limited to bone marrow transplantation with
      its attendant toxicities and limitations. Because the pathophysiology of vaso
      occlusion in sickle cell disease is complex, its treatment will likely be
      optimized using a multifactorial therapeutic approach.

PMID- 9570710
TI  - Molecular insights into early hematopoiesis.
AB  - During embryogenesis, a pool of pluripotential, self-renewing hematopoietic stem
      cells is specified from undifferentiated ventral mesoderm. These cells
      proliferate and differentiate to yield all the peripheral blood lineages.
      Although the mechanisms involved in the commitment and differentiation of
      multipotential progenitors have been well documented, little focus has been
      directed to the molecular events underlying the formation of hematopoietic stem
      cells. In this review we discuss the recent advances made in defining a bone
      morphogenetic protein-responsive signal cascade that regulates the earliest phase
      of blood formation during embryogenesis.

PMID- 9570711
TI  - Bibliography current world literature.

PMID- 9570712
TI  - Influence of systemic arginine-lysine on immune organ function: an
      electrophysiological study.
AB  - To test our hypothesis that arginine (Arg) and lysine (Lys) enhance immune
      activities via neuronal control of the thymus and the spleen, a jugular vein was
      cannulated for amino acid administration in male Wistar rats (approximately 300
      g). In one group (n = 5), an efferent nerve filament of the vagal thymus was
      isolated. In another group (n = 5), splenic nerve efferents were isolated.
      Efferent firing rates were recorded before and for 60-90 minutes after 10 mM Arg
      Lys in 0.5 ml saline intravenously (i.v.). Differences in firing rates were
      evaluated using analysis of variance (ANOVA) and t-test. I.v. Arg-Lys increased
      vagal efferent firing rate to the thymus; enhancing thymic lymphocyte release.
      I.v. Arg-Lys decreased firing rate in splenic efferents; enhancing natural killer
      (NK) cell activity. Therefore, Arg-Lys are detected by hepatoportal sensors,
      stimulating hepatic vagal afferents to the hypothalamus, with the efferent
      neuronal impulses from the hypothalamus modulating immune function in thymus and
      spleen, thereby demonstrating the mechanism of Arg and Lys immune enhancing
      activity.

PMID- 9570713
TI  - Vasopressin neuron activation and Fos expression by stimulation of the caudal
      ventrolateral medulla.
AB  - The present study demonstrates that projections ascending from the caudal
      ventrolateral medulla have direct effects on the expression of the immediate
      early gene c-fos and of the arginine-vasopressin gene in neurosecretory cells of
      the hypothalamic supraoptic nucleus. Intense Fos-like immunoreactivity (Fos-LI)
      was observed in many magnocellular neurons of the supraoptic nucleus after
      electrical stimulation of the caudal ventrolateral medulla. In sham-operated
      rats, Fos-LI was absent or present in very few magnocellular neurons in the
      supraoptic nucleus. Fos-LI was visible in neurons expressing arginine
      vasopressin, and was seen rarely in oxytocin neurons by double-immunostaining
      method. This study showed that 76% of all Fos-positive cells were arginine
      vasopressin immunoreactive, whereas only 4% of them showed oxytocin
      immunoreactivity in the supraoptic nucleus. With in situ hybridization, a high
      level of arginine-vasopressin mRNA was noted in the supraoptic nucleus 3 h after
      stimulation of the caudal ventrolateral medulla; the expression was highest 6 h
      after the stimulation compared with the same region in sham-operated animals.
      These findings suggest that noradrenaline, released from the axon terminals
      originating from the caudal ventrolateral medulla, may participate in the
      regulation of gene transcription of arginine-vasopressin in response to
      physiological stimuli.

PMID- 9570714
TI  - Measurement of local cerebral blood flow by magnetic resonance imaging: in vivo
      autoradiographic strategy using 17O-labeled water.
AB  - Local cerebral blood flow (LCBF) was measured in cats by magnetic resonance
      imaging (MRI), using 17O-labeled water (H[2]17O) as a tracer. Cat brain images
      were obtained using a 256 x 240 matrix fast spin-echo sequence with a total
      acquisition time of 124 seconds per image. Intravenous injection of H(2)17O and
      sampling of arterial blood were simultaneously performed during the MRI scan.
      Injection of H(2)17O over 40 seconds caused a transient decrease in brain signal
      intensity, from which the changes in H(2)17O concentration of brain tissue were
      calculated. The concentration of H(2)17O in arterial blood was measured directly
      by 17O nuclear magnetic resonance (NMR) spectroscopy, and used as an input
      function for the calculation of LCBF. LCBF was successfully determined using an
      in vivo autoradiographic strategy in a total of three cats. In one, LCBF
      measurements were also performed under hypercapnic conditions, and LCBF maps of
      the cat brain during normocapnia and hypercapnia were constructed. These LCBF
      maps reflected well the changes in LCBF induced by hypercapnia, which indicated
      the validity of the used method.

PMID- 9570715
TI  - Disruption of the activity-rest cycle by MAOI treatment: dependence on light and
      a secondary visual pathway to the circadian pacemaker.
AB  - The disruptive effects on the activity-rest cycle of the monoamine oxidase
      inhibitor (MAOI) clorgyline and of continuous light were examined in Syrian
      hamsters. When administered in dim and moderate light intensities, clorgyline
      delayed the daily onset of wheel-running. When administered in bright light, it
      dissociated the circadian rhythm of wheel-running. This dissociation was
      prevented by lesions of the intergeniculate leaflet of the ventral lateral
      geniculate nucleus. Constant darkness restored the circadian rhythm of wheel
      running in hamsters with disrupted circadian rhythms. The phase of the restored
      rhythm of wheel-running was shifted 6-12 h later than the phase of wheel-running
      prior to dissociation. Our results suggest that MAOI treatment weakens the
      coupling between oscillators that comprise the circadian pacemaker, and augments
      the disruptive effects of continuous light acting via the intergeniculate leaflet
      region of the ventral lateral geniculate nucleus. These effects on the circadian
      pacemaker may be responsible for disruptions of the sleep-wake cycle that occur
      as side effects when MAOIs are used clinically to treat depression and might play
      a role in the induction of mania and rapid cycling by antidepressants.

PMID- 9570716
TI  - Receptor-mediated activation of G-proteins by kappa opioid agonists in frog (Rana
      esculenta) brain membranes.
AB  - This study delineates the heterotrimeric guanine nucleotide binding regulatory
      protein (G-protein) types in frog (Rana esculenta) brain membranes and their
      activation by kappa opioid agonists. Ethylketocyclazocine (EKC), trans-(+/-)-3,4
      dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)b enzeneacetamide (U-50,488)
      and bremazocine displayed dose-dependent, norbinaltorphimine-reversible
      stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding
      in crude membrane preparations. G-proteins were identified by Western-blotting
      using previously characterized specific antisera that were generated against
      mammalian G-protein alpha-subunits and beta-subunits. A photoreactive guanosine
      5'-triphosphate (GTP) analog, [alpha-32P]GTP azidoanilide ([alpha-32P]AA-GTP)
      irreversibly labeled four proteins in the molecular weight range of 39-43 kDa.
      Ethylketocyclazocine and U-50,488 stimulated photolabelling of these proteins
      among which the 39 kDa band comigrated with the protein specifically labelled
      with the alpha(i2) antibody and the 40 kDa band was identified as alpha(o1). The
      other two bands were also stained with the alpha(common) antibody, but were not
      further identified. These results suggest that the endogenously expressed kappa
      opioid receptors that are present in frog brain interact with multiple G-proteins
      in situ. Furthermore, the structure of most G-proteins seems to be well preserved
      during phylogenesis.

PMID- 9570718
TI  - Brain dopamine and amino acid concentrations in Lurcher mutant mice.
AB  - Lurcher mutant mice are characterized by massive degeneration of the cerebellum,
      including Purkinje cells and granule cells, as well as for the loss of neurons
      from the inferior olive. Concentrations of dopamine and two of its metabolites
      and of several amino acid neurotransmitters were determined in the cerebellum and
      in other brain regions of these mutants. By comparison to wild-type mice of the
      same background strain, glutamate and taurine concentrations were reduced in the
      Lurcher cerebellum. No decrease was found for aspartate, gamma-aminobutyric acid
      (GABA), glycine, as well as dopamine and its metabolites. Moreover, no
      neurochemical alterations occurred in the brain stem, thalamus, or neostriatum of
      Lurcher mutants. A selective reduction of glutamate concentration was found in
      the hippocampus, while all amino acids measured were decreased in the entorhinal
      piriform areas. These results indicate region-selective reductions of
      neurotransmitter concentrations in a mouse mutant with a defined cerebellar
      cortical pathology.

PMID- 9570717
TI  - Effect of RGH-2716 on learning and memory deficits of young and aged rats in
      water-labyrinth.
AB  - RGH-2716 is a novel 1-oxa-3,8-diazaspiro[4.5] decan 2-one, which was published to
      have potent inhibitory effect on neuronal Na and Ca movement and stimulatory
      action on nerve growth factor (NGF)-production, as well as to show significant
      antiamnesic activity in experimental amnesia models. The aim of the present
      experiments was to study the effect of the compound on the learning process and
      on the different stages of memory using water-labyrinth in normal and memory
      impaired young animals, as well as to study cognitive effect of RGH-2716 on aged
      animals. At the doses of 0.5 mg/kg i.p. or 3 mg/kg p.o. given before daily
      swimming, this compound improved the learning process of young animals impaired
      by either diazepam (DIA) or scopolamine (SCOP). In retrograde amnesia model RGH
      2716 (3 mg/kg p.o.) significantly ameliorated consolidation process and retrieval
      of information impaired by SCOP or DIA. Nimodipine and vinpocetine (10 mg/kg
      p.o.) showed moderate effect compared to RGH-2716. Aged rats pretreated with
      daily i.p. RGH-2716 performed the tasks with significantly fewer errors and
      shorter swimming time than untreated aged rats. When aged animals had to solve a
      new labyrinth problem, treated aged rats showed significantly better learning
      ability than aged controls. One month of oral treatment of aged rats with 3 mg/kg
      dose of RGH-2716 two times daily resulted in a "tendency-like" improvement in
      learning of aged Fischer 344 and spontaneously hypertensive (SH) rats. The
      present results make RGH-2716 an interesting compound for the treatment of
      cognitive disorders.

PMID- 9570719
TI  - Dose-finding study with nimodipine: a selective central nervous system calcium
      channel blocker on aminophylline induced seizure models in rats.
AB  - Nimodipine, a dihydropyridine derivative central nervous system (CNS) selective
      calcium channel blocker was studied at four different dosage schedules in five
      different models of seizures in rats. At a dose of 5 mg/kg, i.p. with
      pretreatment time of 15 min, nimodipine significantly antagonized aminophylline
      (175 and 200 mg/kg, i.p.), electroshock (150 mA for 0.2 s), pentylenetetrazole
      (60 and 75 mg/kg, i.p.), aminophylline (100 mg/kg i.p.) + electroshock (66mA for
      0.2 s), and aminophylline (100 mg/kg, i.p.) + pentylenetetrazole (40 mg/kg, i.p.)
      induced seizures in rats. No hemodynamic alteration was observed with this dose
      of nimodipine. However, 2 mg/kg, i.p. (pretreatment time of 15 min and 30 min)
      and 5 mg/kg, i.p. (pretreatment time of 30 min) doses of nimodipine failed to
      demonstrate any significant anticonvulsant effect. The study highlighted the
      critical role of calcium ion flux into the neurons for the genesis of seizure
      activity to aminophylline, electroshock, and pentylenetetrazole in rats.
      Furthermore, the critical dose requirement for nimodipine could be explained on
      the basis of its short half-life and shorter duration of protection against
      seizures. Therefore, nimodipine may be tried clinically as an anticonvulsant in
      patients who are on aminophylline because of bronchial asthma or chronic
      obstructive pulmonary disease, when such patients have concomitant epilepsy or
      other seizure prone neurological deficits or are scheduled to undergo
      electroshock therapy.

PMID- 9570720
TI  - Effects of halothane and methoxyflurane on regional brain and spinal cord
      substance P-like and beta-endorphin-like immunoreactivities in the rat.
AB  - Effects of acute exposure (2 hr) to either 1.5% halothane or 0.5% methoxyflurane
      were investigated in the Sprague Dawley rat. Pituitary (PIT) and central nervous
      system (CNS) substance P (SP)-like and beta-endorphin (beta-end)-like
      immunoreactivities were evaluated immediately after anesthetic exposure (2 h),
      after righting reflex (4 h) or 24 hr postexposure (24 h). Only halothane
      significantly reduced SP-like immunoreactivity in olfactory bulbs in both the 2-h
      and 4-h groups. Halothane elevated SP-like immunoreactivity of hippocampus at all
      three time periods, and in the hypothalamus at 2 h. Both anesthetics
      significantly depleted thalamic concentrations of SP-like immunoreactivity.
      Methoxyflurane anesthesia resulted in a drastic decrease in SP-like
      immunoreactivity in PIT at all three time periods periods, while halothane
      elevated PIT concentrations of this peptide at 4 h. Both anesthetics
      significantly decreased beta-end-like immunoreactivity in the olfactory bulbs and
      thalami at 2, 4, and 24 h. However, halothane alone significantly elevated beta
      end-like immunoreactivity in the spinal cord at 24 h. Halothane significantly
      elevated PIT beta-end-like immunoreactivity at 2 and 24 h, while methoxyflurane
      significantly lowered it in the 4-h group, but elevated the levels of the same in
      the 24-h group. Brain stem beta-end immunoreactivity were significantly reduced
      at 2 h by both anesthetics, and at 4 h by methoxyflurane. Results indicate that
      halothane and methoxyflurane may differ significantly in their actions on SP and
      beta-end secreting neurons in the CNS.

PMID- 9570721
TI  - Interleukin-1beta system (ligand, receptor type I, receptor accessory protein and
      receptor antagonist), TNF-alpha, TGF-beta1 and neuropeptide Y mRNAs in specific
      brain regions during bacterial LPS-induced anorexia.
AB  - Bacterial lipopolysaccharide (LPS) or endotoxin induces neurological
      manifestations including anorexia. It is proposed that LPS-induced cytokine
      production is involved in the generation of neurological manifestations and in
      neuroinflammatory/immunological responses during gram-negative infections. For
      example, LPS-induced effects can be blocked or ameliorated by the interleukin-1
      receptor antagonist (IL-1Ra). Here, sensitive and specific RNase protection
      assays were used to investigate the effects of the intracerebroventricular
      (i.c.v.) administration of LPS on mRNA levels of interleukin-1beta (IL-1beta)
      system components, tumor necrosis factor (TNF)-alpha, transforming growth factor
      (TGF)-beta1, and neuropeptide Y (NPY) in the cerebellum, hippocampus, and
      hypothalamus. The same brain region sample was analyzed with all of the antisense
      probes. The data show simultaneous local induction of multiple cytokine
      components messenger ribonucleic acids (mRNAs) within specific brain regions in
      anorectic rats responding to i.c.v. administered LPS (500 ng/rat). Interleukin
      1beta and IL-1Ra had a similar mRNA induction profile (hypothalamus > cerebellum
      > hippocampus). Interleukin-1 receptor type I (IL-1RI) mRNA also increased in all
      three brain regions examined, and the soluble form of IL-1 receptor accessory
      protein (IL-1R AcP II) mRNA was induced in the hypothalamus. Tumor necrosis
      factor-alpha mRNA levels increased in the hypothalamus > hippocampus >
      cerebellum. Levels of membrane bound IL-1R AcP, TGF-beta1, and NPY mRNAs did not
      change significantly in any brain region. The results suggest that: (1)
      endogenous up-regulation of IL-1beta and TNF-alpha in the hypothalamus contribute
      to LPS-induced anorexia; and (2) the ratio IL-1Ra/IL-1beta, and IL-1beta <--> TNF
      alpha interactions may have implications for gram-negative infections associated
      with high levels of LPS in the brain-cerebrospinal fluid.

PMID- 9570722
TI  - Secretion and increase of intracellular CuZn superoxide dismutase content in
      human neuroblastoma SK-N-BE cells subjected to oxidative stress.
AB  - CuZn superoxide dismutase (SOD) secretion was detected in media of [35S]cysteine
      labeled human neuroblastoma SK-N-BE cells precipitated with antihuman CuZn SOD
      antibodies. The ability of Fe2+/ascorbate oxidative stress to induce CuZn SOD in
      SK-N-BE cells was evaluated by Western blot analysis. The results showed that,
      like human hepatocarcinoma cells and human fibroblasts, SK-N-BE cells secrete
      CuZn SOD. In addition, the CuZn SOD concentration was higher in cells subjected
      to oxidative stress than in unstressed cells. The secretion of CuZn SOD and the
      ability of Fe2+/ascorbate to increase its protein content in SK-N-BE cells
      indicates that this enzyme protects the brain from damage induced by oxidative
      stress.

PMID- 9570723
TI  - Ca2+-channels involved in neostriatal glutamatergic transmission.
AB  - The actions of peptidic toxins that work as Ca2+-channel antagonists were
      investigated on neostriatal glutamatergic transmission. Both intracellularly
      recorded excitatory postsynaptic potentials (EPSPs) and extracellularly recorded
      population spikes (PS) evoked by afferent stimulation were evaluated in the
      presence of 10 microM bicuculline. Percentage of block (mean +/- SEM; n = 4) for
      these events (EPSP and PS, respectively) was: omega-AgTxIVA (100-200 nM): 35 +/-
      2 and 54 +/- 4%; omega-CgTxGVIA (1 microM): 37 +/- 3 and 63 +/- 6%; omega
      CgTxMVIIC (500 nM): 40 +/- 4 and 50 +/- 2%; and calciseptine (500 nM): 5 +/- 4
      and 9 +/- 6%. When given together, toxins had additive effects. The calciseptine
      effects were nonsignificant. The toxins were also tested on Ca2+-dependent random
      synaptic responses induced by 100 microM 4-AP. Each toxin reduced the frequency
      of spontaneous EPSPs by more than 60% (n = 2). The summed actions of individual
      toxins yields more than 100% block (superadditivity); suggesting that several
      terminals may possess more than one channel type. The reduction in frequency was
      not accompanied by a reduction in amplitude confirming that toxins' actions were
      presynaptic. It is concluded that at least three different Ca2+-channel subtypes
      are involved in glutamate release in neostriatal afferents: N-type, P/Q-type, and
      a type resistant to the toxins used. The L-type Ca2+-channel had little, if any,
      participation.

PMID- 9570724
TI  - Effects of cholinergic deafferentation and NGF on brain electrical coherence.
AB  - Rats received unilateral lesions of the nucleus basalis and were infused
      intracerebroventricularly (i.c.v.) over 3 weeks with nerve growth factor (NGF) or
      vehicle. Electrocortical coherence was assessed at postoperative days 4, 7, 14,
      and 21 from all possible pairs of eight epidural electrodes in the delta (1-4
      Hz), theta (4-8 Hz), alpha (8-12 Hz), beta-1 (12-20 Hz), and beta-2 (20-28 Hz)
      bands. On day 21 choline acetyltransferase (ChAT) activity was measured in
      cortical tissue underlying each electrode site. Lesions resulted in losses of
      interhemispheric, as well as bilateral intrahemispheric coherence in the theta
      band (F1,21 = 28.61, p < 0.0001, F1,21 = 4.30, p < 0.05), with no significant
      differences seen in other bands. Changes were accentuated during immobility
      compared with walking and exploratory behavior. Intrahemispheric changes were
      greatest within the lesioned hemisphere (F1,21 = 6.97, p < 0.01) in long
      connections between electrode pairings connecting frontal to posterior brain
      regions. Nerve growth factor (NGF) attenuated losses in ChAT (F1,21 = 21.31, p <
      0.0001) and intrahemispheric coherence (F1,21 = 9.66, p < 0.005), whereas
      interhemispheric coherence showed no significant response. Intact animals
      receiving NGF showed increases in intrahemispheric coherence, as well as modest
      increases in ChAT. Increases in coherence in response to NGF occurred within 4-7
      days following brain lesions, with no significant change during the 2 weeks
      thereafter. Our results suggest that coherence is sensitive to cholinergic
      deafferentation, particularly of long corticocortical connections. NGF
      differentially restores coherence within hemispheres, as opposed to between
      hemispheres. Our study suggests that brain function in Alzheimer's disease
      related to damage of transcallosal fiber tracts may not be responsive to
      cholinergic treatments. Future studies may wish to evaluate the cognitive
      relevance of NGF's effects on intact brain.

PMID- 9570725
TI  - Glenoid fracture: conservative treatment versus surgical treatment.
AB  - Glenoid fossa fractures are rare. The indication for conservative or surgical
      treatment is controversial, especially because of limited reports in the
      literature. Many authors prefer conservative treatment for most types of glenoid
      fractures to the alternate surgical treatment, but long-term follow-up is rarely
      reported. We report on four patients with displaced, intra-articular glenoid
      fossa, who were treated either surgically or conservatively. After an average 7
      year follow-up, clinical and radiographic results were satisfactory in all
      patients. Based on the literature and our limited experience, we recommend that
      conservative treatment be considered as a good option for displaced intra
      articular glenoid fossa fracture.

PMID- 9570726
TI  - Translaminar lumbar epidural endoscopy: technique and clinical results.
AB  - To provide baseline outcome data for a new lumbar microinvasive diskectomy done
      with standard arthroscopic instrumentation, we retrospectively reviewed the cases
      of 190 patients. All patients were assessed by a modified MacNab outcome
      classification with a minimum of a 2-year follow-up. All complications of this
      procedure were reported as well. No previous outcome data are available for this
      procedure, since it has been done primarily at one center, by the same surgeon,
      using his previously reported techniques. Results were good or excellent in 175
      patients and fair or poor in 15. Complications were not severe and were easily
      remedied. This success rate is comparable to rates reported for other minimally
      invasive operations on the lumbar spine. This new technique of minimally invasive
      lumbar spine surgery provides minimal morbidity and a long-term outcome
      comparable to that of other standard procedures. The added benefits of using
      standard arthroscopic instrumentation are discussed.

PMID- 9570727
TI  - Patellar tendon ACL reconstruction and rehabilitation practices and opinions
      (autograft versus allograft): orthopaedic sports medicine fellowship program
      survey.
AB  - We wanted to determine the bone-patellar tendon-bone (BPTB) anterior cruciate
      ligament (ACL) reconstruction practices of accredited orthopaedic sports medicine
      fellowship programs and their opinions about whether differences should exist in
      rehabilitation protocol, bracing, and timing of release to cutting/agility sports
      between autogeneic and allogeneic grafts. Our survey showed most programs did 51
      to 100 BPTB ACL reconstructions during the 12 months before survey completion.
      Standard rehabilitation protocols were used without differences based on BPTB
      graft type or fixation concerns. Programs were equally divided regarding whether
      BPTB graft type should be a timing of release to cutting/agility sports factor.
      Programs were almost equally divided regarding routinely prescribed derotation
      braces. More programs used autograft rather than allograft BPTB tissue for ACL
      reconstruction, without rehabilitation protocol differences based on graft type
      or fixation concerns. Conflicting results regarding protocol and timing of
      release to cutting/agility sports indicate that several factors may contribute to
      the clinical decision-making process. Equivocal results regarding derotation
      brace prescription raises concerns regarding their necessity.

PMID- 9570728
TI  - Biomechanical analysis of hindfoot fixation using an intramedullary rod.
AB  - To measure the stiffness of the hindfoot when fixed with an intramedullary rod
      placed in a retrograde manner, two biomechanical experiments were carried out on
      five matched pairs of cadaveric below knee specimens. Experiment 1: In the right
      leg of each pair, an intramedullary rod was placed in a retrograde fashion
      through the calcaneus, talus, and into the tibial intramedullary canal.
      Biomechanical testing was done to determine hindfoot stiffness, with and without
      distal and proximal transverse interlocking screws. The uninstrumented left leg
      of each pair was tested as a control. Experiment 2: A series of similar
      biomechanical experiments were done on the same specimens to determine the effect
      on hindfoot stiffness of an intramedullary rod with one distal screw as compared
      with a method of tibiotalocalcaneal fixation using three cross-cannulated screws.
      The results show that an intramedullary rod placed in a retrograde manner
      stiffens the hindfoot and the placement of interlocking screws enhances that
      effect (Experiment 1). The intramedullary rod with one distal screw inserted
      provides more stiffness to the hindfoot than does three cross-cannulated screws
      (Experiment 2).

PMID- 9570729
TI  - The value of serial postoperative radiographs of total knee arthroplasties.
AB  - In a prospective study of 35 cemented press fit condylar knees, we studied the
      prevalence of radiolucent lines 1 mm wide or wider using two methods of
      detection: conventional (plain) and fluoroscopically-guided radiographs. All
      films were evaluated in accordance with the Knee Society Total Knee Arthroplasty
      Roentgenographic Evaluation and Scoring System. A total of 12 radiolucencies were
      detected in nine knees (26% of all knees) using conventional radiographs versus
      25 radiolucencies in 13 knees (37% of all knees) using fluoroscopically-guided
      radiographs. This was a statistically significant difference and suggests that
      the true prevalence of periprosthetic radiolucencies will be underestimated if
      conventional radiographs are used to evaluate the bone-prosthesis interfaces and
      questions the value of routine postoperative plain film radiographs to evaluate
      the results of knee arthroplasty.

PMID- 9570730
TI  - Management of type III acetabular deficiencies in revision total hip arthroplasty
      without structural bone graft.
AB  - Seventeen patients with loose total hip acetabular components and type III
      osteolytic acetabular defects were prospectively identified and reconstructed
      with either spherical acetabular components or eccentric acetabular components
      without use of structural bone graft. A computed tomography (CT) scan and a three
      dimensional (3-D) model were obtained in nine patients to determine whether a
      spherical component or eccentric component should be used. The clinical results
      were measured using the Harris Hip Score. Hip scores improved from 44 to 73
      points for the entire group but were lower in the subgroup with eccentric
      components. Also, two of the eccentric cups developed loosening. The hip center
      was better restored in the eccentric implant group. The cost of the prosthesis
      was higher in the eccentric implant group due to the expenses of the CT scan and
      the 3-D model.

PMID- 9570731
TI  - Chronic osteomyelitis of the tibia: treatment with hyperbaric oxygen and
      autogenous microsurgical muscle transplantation.
AB  - To establish the success rate of combined therapy for tibial osteomyelitis, we
      reviewed all cases of this infection treated with surgery, antibiotics, and
      hyperbaric oxygen (HBO) between 1974 and 1991 at Duke University Medical Center.
      The median delay from diagnosis of osteomyelitis to initiation of HBO was 12.5
      months (range, 1 month to 684 months). Of 34 patients in whom follow-up data were
      complete, 27 (79%) were male and 7 (21%) female, with a mean age of 37.9 years
      (range, 20 years to 77 years). Patients received an average of 8.3 surgical
      procedures (range, 2 to 19) and 35 HBO treatments (range, 6 to 99). Twenty
      patients (59%) received free vascularized muscle flaps as part of therapy.
      Actuarial analysis was used to examine the effect of free vascularized flap
      procedures. Of 26 patients with 24 months of follow-up after treatment, 21 (81%)
      remained drainage free. At 60 months and 84 months after treatment, 12 of 15
      (80%) and 5 of 8 (63%), respectively, were drainage free. After more than 84
      months, patients who had received muscle flaps were more likely to be drainage
      free than patients who had received only debridement, and this difference
      approached statistical significance.

PMID- 9570732
TI  - Malunion/nonunion of radius and ulna shaft fractures.

PMID- 9570733
TI  - Reversal of the histology of bone after parathyroidectomy in patients with
      hyperparathyroidism.
AB  - Hyperparathyroidism is commonly seen in patients with end-stage renal disease and
      less commonly in the primary form. The skeletal manifestations of
      hyperparathyroidism are the same in both forms and are well described in the
      literature. We treated a patient from each category. Multiple bony lesions and
      pathologic fractures were observed. The clinical presentations and radiologic and
      histologic findings confirmed the diagnosis of hyperparathyroidism and osteitis
      fibrosa cystica in both patients. Subtotal excisions of the parathyroid glands
      were done in both patients. Appropriate treatment of the bony lesions and
      pathologic fractures resulted in healing. Histologic evaluation of the bony
      lesions indicated an osteoblastic or healing response. The reversal of the
      histologic pattern in just 5 days and 16 days after parathyroidectomy was noted.
      In treating such patients, physicians should consider parathyroidectomy as an aid
      in the overall management of patients.

PMID- 9570734
TI  - Bilateral bowleg deformity in a child with an adolescent bone age.

PMID- 9570735
TI  - Androgen regulation of the human ornithine decarboxylase promoter in prostate
      cancer cells.
AB  - We studied the response of the human ornithine decarboxylase (ODC) promoter to
      androgen in human prostate cancer cell lines. In the well-differentiated,
      androgen-sensitive human prostate cancer line LNCaP, a genomic ODC promoter
      fragment that includes putative androgen response elements was suppressed by
      androgen. In contrast, the androgen-regulated probasin promoter was induced by
      androgens. The ODC promoter was also induced by cotransfected androgen receptor
      in the poorly differentiated, androgen-insensitive human prostate cancer cell
      line PPC-1. We examined the effects of cotransfected mutant androgen receptors
      containing the LNCaP mutation or DNA-binding mutations. All cotransfected
      androgen receptors switched the ODC androgen response from suppression to
      induction in LNCaP cells. Gel-shift and DNA footprint assays demonstrated
      androgen receptor binding to an ODC sequence that does not contain a consensus
      androgen response element. Deletion of the sequence abolished androgen
      suppression of the ODC promoter. We propose a model of pleiotropic gene
      regulation by androgen that requires a regulatory balance between androgen
      receptor and a transcription factor binding to the nonconsensus androgen response
      element.

PMID- 9570736
TI  - Epididymal obstruction during development results in antisperm autoantibodies at
      puberty in rats.
AB  - An autoimmune response to sperm occurs after vasectomy, but there is little
      information on whether similar reactions occur after obstruction of the male
      reproductive tract at other points. Male Lewis rats received bilateral ligation
      of the corpus epididymidis or a sham operation at age 10 days, and the subsequent
      systemic antisperm autoantibody responses were compared to those observed
      following obstruction of the vas deferens. After sexual maturation, rats with
      epididymal ligations had antisperm antibodies on an enzyme-linked immunosorbent
      assay that were significantly higher than those of sham-operated animals and did
      not differ from antibody levels in vasectomized rats at the same ages. Western
      blot analysis showed that certain sperm proteins were recognized by antisperm
      antibodies after both epididymal ligation and vasectomy, including the previously
      identified "dominant" autoantigens at 73-83, 68-72, 48, 42, and 22 kDa. On the
      other hand, sera from rats with epididymal ligations recognized 60 and 52 kDa
      proteins that were not bound by most postvasectomy sera. Conversely, 42-48 and 38
      42 kDa bands were more strongly and frequently stained after vasectomy than after
      epididymal ligation. The results demonstrate that antisperm antibodies are
      produced after obstruction of the epididymis and that the magnitude of the
      response is comparable to that after vasal obstruction. Differences in
      autoantigens recognized after epididymal and vasal obstructions may reflect
      maturational changes in sperm components that take place during the passage of
      spermatozoa through the epididymis.

PMID- 9570737
TI  - Altered basement membrane synthesis in the testis after tissue injury.
AB  - The basement membrane plays an important role in maintaining the structural and
      functional integrity of tissues. Altered basement membrane structure has been
      associated with severe functional impairment of the testis in several conditions,
      including vasectomy, autoimmune orchitis, cryptorchidism, and following x
      irradiation. We have used efferent duct ligation as a model to examine
      seminiferous tubular basement membrane morphology, synthesis, and gene expression
      to determine whether altered basement membrane synthesis is responsible for the
      aberrant structures noted after tissue injury. On days 2 and 3 after ligation,
      both the seminiferous epithelium and the basement membrane appeared normal, but 7
      days after ligation, the seminiferous epithelium began to degenerate. The
      basement membrane appeared detached from the epithelium, and redundant patches of
      basement membrane were observed adjacent to the Sertoli cells at 14 and 21 days
      postligation. Immunoprecipitation indicated an increase in laminin protein
      synthesis in the ligated tubules at the same time. Northern blot analysis showed
      increases in transcript levels for laminin as well as collagen IV and heparan
      sulfate proteoglycan. These data show that new protein synthesis is responsible,
      at least in part, for the duplication of the basement membrane coincident with
      the tissue damage caused by efferent duct ligation.

PMID- 9570738
TI  - Distribution of mouse sulfated glycoprotein-1 (prosaposin) in the testis and
      other tissues.
AB  - Mouse sulfated glycoprotein-1 (SGP-1) is the homologue of rat SGP-1 and human
      prosaposin. Rat SGP-1 is one of the major secretory products of rat Sertoli cells
      in culture. Human prosaposin is the precursor of four lysosomal saposins, termed
      A, B, C, and D, that are generated by limited proteolysis. Saposins are
      sphingolipid-binding proteins that function as activators for lysosomal enzymes
      involved in sphingolipid hydrolysis of the former. Recently, we have generated a
      cDNA encoding the mouse SGP-1 by polymerase chain reaction amplification of a
      mouse testicular Uni-Zap XR cDNA library with two synthetic oligonucleotide
      primers and have used it as a probe for examining the tissue distribution of SGP
      1 mRNA. We have also studied the distribution of the translation product of SGP-1
      mRNA in the same tissues. The analysis demonstrated that SGP-1 is expressed
      ubiquitously in all tissues examined. This investigation showed that, in mouse
      testis, two forms of SGP-1 exist: a 70-kDa secreted protein and a 65-kDa protein
      corresponding to the lysosomal form of SGP-1, which may be involved in the
      generation of saposins. Light microscope immunocytochemistry with anti-SGP-1
      antibody demonstrated that, in the mouse seminiferous tubules, the translation
      product of SGP-1 mRNA is expressed in Sertoli cells but not in germinal cells.
      Electron microscope immunogold labeling with anti-SGP-1 antibody yielded a strong
      reaction on lysosomes and phagolysosomes containing residual bodies but not on
      endosomes or luminal residual bodies. These results demonstrate that SGP-1 is not
      internalized from the lumen but is targeted directly to the lysosomes from the
      Golgi apparatus. Immunoblotting also confirmed the existence of a secreted form
      of testicular SGP-1 delivered to the lumen of the seminiferous tubules. The
      production of a secreted and a lysosomal form of SGP-1 by Sertoli cells indicates
      that this protein plays a multifunctional role. This study also suggests that the
      lysosomal form of SGP-1 may be involved in the degradation of membrane
      glycolipids from residual bodies phagocytosed by Sertoli cells.

PMID- 9570739
TI  - Mouse testicular sulfated glycoprotein-1: sequence analysis of the common
      backbone structure of prosaposins.
AB  - We have generated a cDNA encoding the mouse sulfated glycoprotein-1 (SGP-1) by
      polymerase chain reaction amplification of a mouse testicular Uni-Zap XR cDNA
      library with two synthetic oligonucleotide primers. A positive signal of 1,959
      bases was isolated and subcloned into the pGEM-T. Sequence analysis showed a near
      identical nucleotide and amino acid similarity to mouse prosaposin cDNA. A few
      amino acid differences were found, and they may represent strain-specific
      heterogeneities. The cDNA has 88% amino acid identity to rat SGP-1 and 64%
      identity to human prosaposin. Prosaposin is the precursor of four lysosomal
      saposins (A, B, C, and D) that are generated by the proteolytic maturation of the
      former. Saposins are sphingolipid binding proteins that function as activators of
      lysosomal enzymes involved in sphingolipid hydrolysis. Northern blot analysis
      demonstrated that SGP-1 mRNA is transcribed in the seminiferous epithelium by
      Sertoli cells but not by germinal cells. Our results also demonstrated two forms
      of alternatively spliced testicular SGP-1 mRNA. This alternative splicing results
      in the inclusion or exclusion of exon 8, which encodes for three amino acid
      residues (QDQ) that are implicated in the sphingolipid binding affinity of
      saposin B. Sequence aligment indicates that all saposins share a common motif
      characterized by six conserved cysteines, a conserved N-linked glycosylation
      site, a conserved proline residue, and 15 positions that are characterized by
      large hydrophobic amino acids. These characteristics, together with similar
      secondary structure predictions and the predicted similar formation of three
      disulfide linkages, create a common framework of amino acids of three alpha
      helices enclosing an internal hydrophobic core for all saposins. The disulfide
      placement data, the hydropathy profile, and the presence of amphiphatic helices
      indicate that all saposins are stable proteins sharing similar secondary and
      tertiary structures.

PMID- 9570740
TI  - Levels of hepatocyte growth factor/scatter factor (HGF/SF) in seminal plasma of
      patients with andrological diseases.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) has all the characteristics of a
      molecule suitable for functioning in regulatory networks of motility, such as the
      spermatogenic epithelium, where spermatogenic cells must migrate between the
      cells of Sertoli, and it exerts its effect through binding of its high-affinity
      receptor (c-met). Considering the findings that c-met receptor is expressed in
      the human testis and on spermatozoa, and that HGF/SF in seminal plasma consists
      of pro-HGF/SF, mature alphabeta-HGF/SF, and less active forms of HGF/SF, we
      investigated the concentration and biological activity of HGF/SF in seminal
      plasma and their correlation with parameters of spermatogenesis to obtain better
      insight into mechanisms that may be involved in the pathogenesis of male
      infertility. We also evaluated the potential value of assessment of hepatocyte
      growth factor concentration and its bioactivity for the diagnosis of certain
      pathological conditions of male reproduction. We studied the concentration and
      biological activity of HGF/SF in seminal plasma of normal men and of patients
      with a range of andrological diseases or conditions by measuring HGF/SF in
      seminal plasma by enzyme-linked immunosorbent assay and by scatter assay using
      Madin-Darby canine kidney epithelial cells. We identified three sources of HGF/SF
      in seminal plasma. In samples from vasectomized men (n = 30; 2.01 ng/ml) and in
      split ejaculate samples (n = 6; 1e fraction 2.75 ng/ml, 2e fraction 1.62 ng/ml),
      a prostatic origin can be certified. This HGF/SF has low biological activity
      (133.3 U/ml). In inflammation of the accessory sex glands (n = 40), a high amount
      of HGF/SF (3.04 ng/ml) can be generated by white blood cells and has moderate
      scatter activity (426.7 U/ml). In normozoospermic samples, there is a lower
      amount of HGF/SF (1.12 ng/ml), with strong scatter activity (1280.0 U/ml).
      Finally, the clear difference between the low amount of HGF/SF (1.06 ng/ml) with
      poor scatter activity (106.6 U/ml) in oligozoospermic samples (n = 28) and the
      high amount of HGF/SF (3.35 ng/ml) with strong scatter activity (853.3 U/ml) in
      samples from men with azoospermia of primary testicular failure (n = 18) suggests
      a mainly testicular origin, with different activity in different pathological
      conditions.

PMID- 9570741
TI  - Sequence divergence within the sperm-specific polypeptide TCTE1 is correlated
      with species-specific differences in sperm binding to zona-intact eggs.
AB  - The T-complex-associated testes-expressed (TCTE1) gene encodes a novel sperm cell
      specific polypeptide (TCTE1) that is conserved across vertebrate species. TCTE1
      is absolutely required for fertilization and is expressed in earlier stages of
      spermatogenesis. When the amino acid sequence of the TCTE1 gene product is
      compared among various mammalian species, a large, highly conserved domain is
      observed, along with a divergent domain encoding the 56-58 residues at the N
      terminus. In this study, the N-terminal regions of the TCTE1 polypeptide from
      three rodent species--mouse, gerbil, and rat--were compared. The results show
      that while the gerbil and mouse species are most distant in evolutionary terms,
      their TCTE1 homologs have not undergone significant divergence. In contrast, the
      N-terminal region of the rat TCTE1 homolog has evolved rapidly, a finding that
      indicates positive Darwinian selection. We have tested the correlation between
      TCTE1 divergence and heterospecific sperm-egg binding ability in the three
      species under study. Gerbil sperm bind to mouse eggs, while no significant
      binding is observed between rat sperm and mouse eggs. The results obtained
      support the hypothesis that the sperm-specific polypeptide TCTE1 may facilitate
      species-specific divergence of sperm function.

PMID- 9570742
TI  - A panel of monoclonal antibodies against human sperm.
AB  - To help identify and characterize antigens involved in sperm functions and immune
      infertility, monoclonal antibodies (mAbs) were raised against human sperm
      antigens. The immunoglobulin G (IgG) fraction of serum from a male donor with a
      spontaneous high titer of IgG-positive antisperm reactivity (as determined by
      immunobead binding) was purified by ammonium sulfate precipitation. This IgG
      preparation was coupled to Sepharose 4B and was used for immunoaffinity
      purification of antigens from a detergent-solubilized extract of pooled normal
      human sperm. The affinity-purified antigens were used to immunize female mice,
      and the resultant spleen cells were fused with SP 2/0 mouse myeloma cells to
      generate hybridomas. A single-step semisolid methylcellulose method was used to
      isolate hybridomas for the selection of positive clones, which were determined by
      enzyme-linked immunosorbent assay. Thirty-two positive hybridoma lines were
      selected for immunolocalization and cross-reactivity studies using an avidin
      biotin complex assay. Distinctive staining patterns and distribution of sperm
      antigens were observed for 10 mAbs. Among them, the cross-reactivity with human
      lymphocytes was not observed for four mAbs.

PMID- 9570743
TI  - Round spermatids from prepubertal mouse testis can develop into normal offspring.
AB  - We investigated fertilization and embryo development after intracytoplasmic
      injection of round spermatids collected from mice before puberty. The rates of
      normal fertilization, blastocyst formation, and development into live offspring
      were examined. The injection of oocytes with round spermatids from mature or
      prepubertal males resulted in similar rates of normal fertilization and embryo
      development. The rates of the development to term of two-cell embryos were also
      similar, regardless of the origin of the round spermatids injected. This finding
      suggests that round spermatids from the prepubertal testis already have the
      ability to fertilize normally and to allow normal embryo development.

PMID- 9570744
TI  - Use of Hoechst 33342 stain to evaluate live fresh and frozen bull sperm by
      computer-assisted analysis.
AB  - The objective of this research was to investigate possible procedures for
      evaluating living bull sperm stained with Hoechst 33342 while in a simple medium
      and in commonly used complex egg yolk-glycerol-Tris (EYGT) and whole milk
      glycerol (WMG) extenders. The two semen extenders provide good cryoprotection,
      but the latter one virtually obscures the sperm. To evaluate sperm motion
      characteristics when static nonsperm particles are present, a new Hamilton Thorne
      epifluorescent optical system (UV) with a strobe light was developed for
      potential use with DNA-stained sperm. This system permitted examination for the
      first time of sperm motion characteristics in milk. In Experiment 1 (four bull
      semen replicates with five dye concentrations and three incubation times), 2.5
      microg/ml of Hoechst 33342 stained live and dead sperm sufficiently in a modified
      Tyrode's solution to measure all sperm characteristics without depressing
      motility, which was validated by using phase-contrast to analyze stained and
      unstained controls. In Experiments 2a and 2b, each using semen from four bulls
      with a 5 x 5 factorial arrangement, it was determined that 40 to 60 microg/ml of
      dye in EYGT or WMG, with UV illumination for 20 minutes, was optimal. There was
      no detrimental effect on sperm motility. In Experiment 3, analyses of two
      ejaculates, from each of eight bulls, confirmed that motion characteristics of
      sperm in EYGT and WMG were not depressed when the sperm were stained with Hoechst
      33342. These experiments demonstrate that the dye concentrations and exposure
      times developed for use with the new epifluorescent optics facilitate evaluating
      bull sperm frozen in particle-filled whole milk and should be useful for sperm
      evaluation of a variety of species when nonsperm particulate matter may otherwise
      interfere.

PMID- 9570745
TI  - The effects of antifreeze peptide III (AFP) and insulin transferrin selenium
      (ITS) on cryopreservation of chimpanzee (Pan troglodytes) spermatozoa.
AB  - We investigated the effects of antifreeze peptides (AFP) and insulin transferrin
      selenium (ITS) on the motility and membrane integrity of chimpanzee (Pan
      troglodytes) spermatozoa after chilling (0-5 degrees C) and thawing. The effects
      of three thawing procedures, in the presence or absence of AFP and ITS, on sperm
      motility and on the status of the plasma membrane and acrosome were also
      examined. During chilling, AFP and ITS seem mildly cytotoxic, as the progressive
      motility and velocity (curvilinear and straight line) declined significantly at
      AFP concentrations of 1, 10, and 100 microg/ml and at ITS concentrations of 1 and
      10 microg/ml. However, at a concentration of 100 microg/ml, ITS was able to
      protect sperm during short-term hypothermic storage. Addition of AFP or ITS at
      100 microg/ml to test egg yolk-glycerol extender during freezing significantly (P
      < 0.05) increased postthaw motility, plasma membrane integrity, and acrosome
      integrity. The mean (+/-SE) motility recovery rate increased from 28.9 +/- 3.9%,
      for the untreated control, to 59.2 +/- 5.8% and 67.8 +/- 7.4%, for ITS and AFP,
      respectively. The effects of the thawing procedure were influenced by the
      presence of AFP during the freezing cycle. An improved motility recovery rate of
      67 +/- 4.2% was obtained when chimpanzee sperm frozen in test egg yolk-glycerol
      extender supplemented with AFP were thawed rapidly at 37 degrees C, compared to
      47 +/- 5.2% and 44 +/- 8.2% for slow (23 degrees C) and ultrarapid (75 degrees C)
      thawing, respectively. The motility recovery after thawing of ITS-treated semen
      at 23 degrees C, 37 degrees C, or 75 degrees C was not significantly different.
      Semen frozen without AFP or ITS and thawed at 75 degrees C was seriously (P <
      0.05) damaged. This study provides evidence that AFP- or ITS-supplemented semen
      extender improves postthaw sperm motility in the chimpanzee.

PMID- 9570746
TI  - Human sperm capacitation induced by biological fluids and progesterone, but not
      by NADH or NADPH, is associated with the production of superoxide anion.
AB  - Recent evidence indicated that human sperm capacitation is associated with an
      increased production of superoxide anion (O2.-). To further study the role and
      importance of O2.- in capacitation, we investigated whether the O2.- generation
      is a general feature of capacitating spermatozoa, irrespective of the inducer
      used, and is correlated with capacitation levels and increased tyrosine
      phosphorylation of two sperm proteins (p105/p81). We also studied the time
      courses of O2.- production and action. Percoll-washed human spermatozoa were
      incubated in Ham's F-10 medium, supplemented or not supplemented with various
      capacitation inducers and in the presence or absence of superoxide dismutase
      (SOD). Sperm capacitation was measured by induction of the acrosome reaction with
      lysophosphatidylcholine, O2.- production was measured by chemiluminescence, and
      tyrosine phosphorylation was measured by immunodetection after electrophoresis
      and western blotting of sperm proteins. Progesterone and ultrafiltrates of human
      fetal cord serum, follicular fluid, and seminal plasma individually promoted
      sperm generation of O2.-, tyrosine phosphorylation of p105/p81, and capacitation.
      Fetal cord serum ultrafiltrate triggered a fivefold higher O2.- production than
      the other inducers (1,700 +/- 300 and 300 to 400 mV/10s/8 x 10(6) cells,
      respectively), a phenomenon possibly associated with the higher potency of this
      fluid to promote sperm hyperactivation. The production of O2.- by spermatozoa was
      rapid and transient. SOD prevented sperm capacitation triggered by the inducers
      mentioned above, but only when SOD was added at the beginning of incubation, and
      not after 30 minutes, indicating that the O2.- initiates a chain of early events
      leading to sperm capacitation. NADH and NADPH (5 mM) triggered sperm capacitation
      and phosphorylation of p105/p81, but these processes were not prevented by SOD or
      catalase, nor were they associated with an increased O2.- production. Therefore,
      these cofactors appeared to act by mechanisms different from those used by the
      other inducers studied. The sperm enzyme responsible for the O2.- generation may
      be very different from the NADPH oxidase of neutrophils.

PMID- 9570747
TI  - Single-step isolation of bovine seminal platelet-activating factor
      acetylhydrolase.
AB  - Bovine seminal platelet-activating factor acetylhydrolase was isolated to >90%
      purity in a single step using a butyl sepharose column. The procedure involves
      the elution of the activity by use of an ethanol gradient. Protein binds readily
      to the resin in the absence of high ionic strength and elutes as a peak centered
      at 30% ethanol. Approximately 2 mg (by Bradford; 5 mg by weight) of the enzyme
      can thus be easily obtained from 9 ml of seminal plasma. The specific activity of
      the purified protein was 22 micromol/minute/mg. About 10% of the loaded activity
      systematically passed unadsorbed through the column, even after repassing. Most
      of this activity, however, was attributed to the same or a very similar enzyme
      that cross-reacts with polyclonal antibodies directed against the highly purified
      platelet-activating factor acetylhydrolase. The enzyme was acid-labile but very
      resistant to freezing and lyophilization. This purification procedure should
      constitute a valuable asset to investigators interested in platelet-activating
      factor and platelet-activating factor acetylhydrolase roles in reproductive
      biology.

PMID- 9570748
TI  - Influence of centrifugation regimes on motility, yield, and cell associations of
      mouse spermatozoa.
AB  - Mouse sperm are exceptionally sensitive to mechanical forces associated with
      pipetting and mixing. This characteristic raised the question of the sensitivity
      of mouse sperm to centrifugation, a step necessary in the removal of
      cryoprotectants and a common component in the general manipulation of sperm
      suspensions for experimental purpose. Epididymal spermatozoa from ICR mice were
      isolated and manipulated to minimize pipetting and mixing damage. The centrifugal
      accelerations studied were 200, 400, 600, and 800 x g (measured with a
      stroboscope) for 5, 10, or 15 minutes of centrifugation time. The number of cells
      and the number of motile cells were counted. The percent motility and longevity,
      total yield, and motile yield were calculated. Centrifugation at 200 and 400 x g
      for short times (5 minutes) caused only a small loss in either immediate or 2.5
      hour motility, but centrifugation at 600 and 800 x g for 15 minutes produced up
      to a fivefold loss. Low speed/short time centrifugation pelleted only about half
      of the cells; the others were lost when the supernatant was removed. The maximum
      number of motile sperm (motile yield) was obtained at intermediate centrifugal
      forces (approximately 400 x g for 10-12 minutes), and it is the total number of
      motile sperm (and not the percent motility) that is important in the use of
      cryopreserved sperm to regenerate cryopreserved mutant lines. Relative
      centrifugal force and centrifugation time exhibit reciprocity (e.g., 200 x g for
      10 minutes produces similar results to 400 x g for 5 minutes). The spermatozoa
      must be centrifuged under carefully defined conditions to minimize the damage and
      to maximize the recovery of viable cells.

PMID- 9570749
TI  - The molecular basis of sperm capacitation.

PMID- 9570750
TI  - Ret finger protein is a normal component of PML nuclear bodies and interacts
      directly with PML.
AB  - The ret finger protein (rfp) is a member of the B-box zinc finger gene family
      many of which may function in growth regulation and in the appropriate context
      become oncogenic. Members of this family are nuclear proteins that possess a
      characteristic tripartite motif consisting of the RING and B-box zinc binding
      domains and a coiled-coil domain. The promyelocytic leukemia gene (PML), another
      B-box family member, produces a protein product that is detected within punctate
      nuclear structures called PML nuclear bodies (NBs) or PML oncogenic domains
      (PODs). These NBs are complex structures that consist of a number of different
      proteins many of which have yet to be identified. In the disease acute
      promyelocytic leukemia (APL) a fusion protein, PML-RARA, is produced through the
      t(15:17) translocation. In APL the morphology of the NBs is altered. We report
      that rfp co-localizes with PML in a subset of the PML NBs and that it interacts
      directly with PML. This interaction is mediated through the rfp B-box and the
      distal two coils. In contrast, homomultimerization of rfp preferentially involves
      the B-box and the proximal coil. The association of rfp with the PML NBs is
      altered by mutations that affect rfp/PML interaction and in NB4 cells that are
      derived from APL patients. When treated with retinoic acid, rfp reassociates with
      the NBs in a pattern similar to non APL cells. Additionally, we found that rfp
      colocalizes with PML-RARA protein produced in APL patients. These results suggest
      that rfp, along with the other known/unknown components of PML NBs, have an
      important role in regulating cellular growth and differentiation.

PMID- 9570751
TI  - Protein phosphatase 4 is an essential enzyme required for organisation of
      microtubules at centrosomes in Drosophila embryos.
AB  - The protein serine/threonine phosphatase 4 (PP4), which localises to
      centrosomes/spindle pole bodies in human cells, is shown to exhibit a similar
      localisation in Drosophila cells and embryos and possess a highly conserved (91%
      identical) amino acid sequence from humans to invertebrates. A homozygous
      Drosophila melanogaster strain mutant in the PP4 gene at 19C1-2 has been produced
      using P element mutagenesis. This strain, termed centrosomes minus microtubules
      (cmm), has reduced amounts of PP4 mRNA, approximately 25% of normal PP4 protein
      in early embryos and exhibits a semi-lethal phenotype with only 10% viability in
      certain conditions. Reversion mutagenesis shows that the phenotype is due to the
      presence of the P element in the PP4 mRNA. In early cmm embryos, nuclear
      divisions become asynchronous and large regions containing centrosomes with no
      well defined radiating microtubules are visible. In such areas, most nuclei
      arrest during mitosis with condensed DNA, and mitotic spindle microtubules are
      either absent, or aberrant and unconnected to the centrosome. A reduction in the
      staining of gamma-tubulin at centrosomes in cmm embryos suggests a conformational
      change or relocation of this protein, which is known to be essential for
      initiation of microtubule growth. These findings indicate that PP4 is required
      for nucleation, growth and/or stabilisation of microtubules at
      centrosomes/spindle pole bodies.

PMID- 9570752
TI  - Identification and functional characterization of a novel human protein highly
      related to the yeast dynamin-like GTPase Vps1p.
AB  - Dynamin proteins containing a GTPase domain, a pleckstrin homology motif and a
      proline-rich tail participate in receptor-mediated endocytosis in organisms
      ranging from insects to vertebrates. In addition, dynamin-related GTPases, such
      as the yeast Golgi protein Vps1p, which lack both the pleckstrin homology motif
      and the proline-rich region, participate in vesicular transport within the
      secretory pathway in lower eukaryotes. However, no data is available on the
      existence of Vps1p-like proteins in mammalian cells. In this study, we report the
      identification and characterization of a novel gene encoding a human dynamin
      related protein, DRP1, displaying high similarity to the Golgi dynamin-like
      protein Vps1p from yeast and to a Caenorhabditis elegans protein deposited in the
      databank. These proteins are highly conserved in their N-terminal tripartite
      GTPase domain but lack the pleckstrin homology motif and proline-rich region.
      Northern blot analysis reveals that the DRP1 mRNA is detected at high levels in
      human muscle, heart, kidney and brain. Immunolocalization studies in Chinese
      hamster ovary (CHO) cells using an epitope-tagged form of DRP1 and confocal
      microscopy show that this protein is concentrated in a perinuclear region that
      labels with the endoplasmic reticulum marker DiOC6(3) and the Golgi marker C5-DMB
      Cer. In addition, the localization of DRP1 is highly similar to the localization
      of the endoplasmic reticulum and cis-Golgi GTPase Rab1A, but not to the staining
      for the trans-Golgi GTPase Rab6. Furthermore, overexpression of a cDNA encoding a
      GTP binding site mutant of DRP1 (DRP1(K38E)) in CHO cells decreases the amount of
      a secreted luciferase reporter protein, whereas the overexpression of wild-type
      DRP1 increases the secretion of this marker. Together, these results constitute
      the first structural and functional characterization of a mammalian protein
      similar to the yeast dynamin-related GTPase Vps1p and indicate that the
      participation of these proteins in secretion has been conserved throughout
      evolution.

PMID- 9570753
TI  - Inhibition of GSK-3beta leading to the loss of phosphorylated MAP-1B is an early
      event in axonal remodelling induced by WNT-7a or lithium.
AB  - WNT-7a induces axonal spreading and branching in developing cerebellar granule
      neurons. This effect is mediated through the inhibition of GSK-3beta, a
      serine/threonine kinase and a component of the WNT pathway. Lithium, an inhibitor
      of GSK-3beta, mimics WNT-7a in granule cells. Here we examined further the effect
      of GSK-3beta inhibition on cytoskeletal re-organisation. Lithium induces axonal
      spreading and increases growth cone area and perimeter. This effect is associated
      with the absence or reduction of stable microtubules in spread areas. Lithium
      induces the loss of a phosphorylated form of MAP-1B, a microtubule associated
      protein involved in axonal outgrowth. Down-regulation of the phosphorylated MAP
      1B, MAP-1B-P, from axonal processes occurs before axonal remodelling is evident.
      In vitro phosphorylation assays show that MAP-1B-P is generated by direct
      phosphorylation of MAP-1B by GSK-3beta. WNT-7a, like lithium, also leads to loss
      of MAP-1B-P from spread axons and growth cones. Our data suggest that WNT-7a and
      lithium induce changes in microtubule dynamics by inhibiting GSK-3beta which in
      turn lead to changes in the phosphorylation of MAP-1B. These findings suggest a
      novel role for GSK-3beta and WNTs in axonal remodelling and identify MAP-1B as a
      new target for GSK-3beta and WNT.

PMID- 9570754
TI  - Clustering of pericentromeres initiates in step 9 of spermiogenesis of the rat
      (Rattus norvegicus) and contributes to a well defined genome architecture in the
      sperm nucleus.
AB  - Fluorescence in situ hybridization with centromeric, telomeric and whole
      chromosome paint probes was used to study nuclear topology in epididymal sperm as
      well as spermatids from testis tissue sections of the rat. Pericentromeric
      regions of 9 chromosomes of the rat (n=21) were labeled with a satellite I
      specific DNA probe. Pericentromeres showed few tandem associations in spermatids
      of steps 1-8 of spermiogenesis. At step 9, pericentromeric regions associated to
      form an elongated cluster in the spermatid nucleus. This arrangement was also
      seen in the sperm nucleus. FISH with telomere probes revealed numerous, variably
      arranged signals in round and elongated spermatids as well as sperm nuclei.
      Telomere signals showed a tendency for pairwise association which was more
      pronounced in elongated spermatid and epididymal sperm nuclei. FISH to DTT
      treated sperm suggested that telomeres reside at the periphery and that
      pericentromeres are located in the nuclear interior. Chromosome painting with rat
      chromosome 2 and 12 specific microdissection library probes showed that these
      chromosomes predominantly occupy compact and variably shaped territories during
      spermatid maturation. In elongated epididymal sperm nuclei chromosome 2 and 12
      territories took up specific positions. We suppose that the associations of
      pericentromeres during step 9 render a well defined nuclear topology which
      facilitates the ordered compaction of the genome at subsequent stages.

PMID- 9570755
TI  - The TOGp protein is a new human microtubule-associated protein homologous to the
      Xenopus XMAP215.
AB  - We have recently identified a 6,449 bp cDNA, termed colonic, hepatic tumor over
      expressed gene (ch-TOG), that is highly expressed in human tumors and brain. Its
      single open reading frame encodes a putative 218,000 Da polypeptide, TOGp.
      Antibodies generated against a bacterially expressed TOGp fragment specifically
      recognize a 218, 000 Da polypeptide in two human cell lines and in brain.
      Immunofluorescence microscopy using affinity-purified TOGp antibodies revealed
      that the distribution of TOGp was dependent upon the cell cycle. During
      interphase, TOGp was found concentrated in the perinuclear cytoplasm, where it co
      localized with ER markers. In contrast anti-TOGp antibodies stained centrosomes
      and spindles in mitotic cells. TOGp co-sedimented with taxol-stabilized
      microtubules in vitro. Moreover, a TOGp enriched fraction promotes microtubule
      assembly both in solution and from nucleation centers. Finally, sequence
      comparison and immunologic cross-reaction suggest that TOGp is homologous to
      XMAP215, a previously described microtubule associated protein (MAP) from Xenopus
      eggs. These results suggest that TOGp is a MAP and that TOGp/XMAP215 may be
      necessary for microtubules rearrangements and spindle assembly in rapidly
      dividing cells.

PMID- 9570756
TI  - Fibronectin is a survival factor for differentiated osteoblasts.
AB  - The skeletal extracellular matrix produced by osteoblasts contains the
      glycoprotein fibronectin, which regulates the adhesion, differentiation and
      function of various adherent cells. Interactions with fibronectin are required
      for osteoblast differentiation in vitro, since fibronectin antagonists added to
      cultures of immature fetal calvarial osteoblasts inhibit their progressive
      differentiation. To determine if fibronectin plays a unique role in fully
      differentiated osteoblasts, cultures that had already formed mineralized nodules
      in vitro were treated with fibronectin antagonists. Fibronectin antibodies caused
      >95% of the cells in the mature cultures to display characteristic features of
      apoptosis (nuclear condensation, apoptotic body formation, DNA laddering) within
      24 hours. Cells appeared to acquire sensitivity to fibronectin antibody-induced
      apoptosis as a consequence of differentiation, since antibodies failed to kill
      immature cells and the first cells killed were those associated with mature
      nodules. Intact plasma fibronectin, as well as fragments corresponding to the
      amino-terminal, cell-binding, and carboxy-terminal domains of fibronectin,
      independently induced apoptosis of mature (day-13), but not immature (day-4),
      osteoblasts. Finally, transforming growth factor-beta1 partially protected cells
      from the apoptotic effects of fibronectin antagonists. Thus, in the course of
      maturation cultured osteoblasts switch from depending on fibronectin for
      differentiation to depending on fibronectin for survival. These data suggest that
      fibronectin, together with transforming growth factor-beta1, may affect bone
      formation, in part by regulating the survival of osteoblasts.

PMID- 9570757
TI  - Modulation of gap junction expression during transient hyperplasia of rat
      epidermis.
AB  - Retinoids and phorbol esters have profound effects on proliferation and
      differentiation of epidermal keratinocytes when applied topically on rodent skin.
      Since both agents also modulate gap junction (GJ)-mediated cell-cell
      communication, we have examined the effects of all-trans retinoic acid (RA) and
      12-O-tetradecanoylphorbol-13-acetate (TPA) on the expression of alpha1 (Cx43) and
      beta2 (Cx26) connexins, the two major gap junction gene products in mature rat
      epidermis. In fully differentiated, mature epidermis, alpha1 is expressed in the
      lower, less differentiated portion, while beta2 is localized in upper, more
      differentiated layers. Dorsal skin of 21-day old rats was treated topically with
      a single dose of RA, TPA or vehicle alone and used for histological and molecular
      analyses at different time points. Keratinocytes in interfollicular epidermis
      were examined for proliferation and differentiation using specific antibodies for
      keratins (K10, K14) and proliferating cell nuclear antigen (PCNA). An increase in
      epidermal thickness was noticed within 4 hours after the application of RA or
      TPA. This increase, however, appeared to be primarily due to hypertrophy, since
      no substantial changes were observed in the proliferative index of epidermal
      keratinocytes. PCNA immunoreactivity significantly increased after 8 hours
      treatment of RA or TPA, suggesting a hyperproliferative growth response.
      Epidermal hyperplasia was confirmed by monitoring the expression patterns of K10
      and K14 in RA- or TPA-treated skin. RA-induced hyperplasia lasted longer as
      compared to TPA induction. Changes in keratin phenotypes were paralleled by an
      increase in alpha1 and beta2 connexin expression as well as their colocalization
      in same epidermal layers. Differences in hyperplastic growth response kinetics
      were also confirmed at the connexin level, with beta2 antigen sustained for
      longer and at higher levels in suprabasal layers of RA-treated skin. Overall,
      this type of connexin expression resembled that observed in the non
      differentiated rat epidermis during embryonic development. An increase in alpha1
      and beta2 connexin abundance was also observed at the protein and RNA levels. At
      96 hours after RA or TPA treatment, expression of both connexins was similar to
      that of the control epidermis. Taken together, these findings suggest that a
      higher level of GJ-mediated cell-cell communication, is required for the
      maintenance of homeostasis during periods of rapid epidermal growth and
      differentiation.

PMID- 9570758
TI  - Lipocortin 1 (annexin 1) in patches associated with the membrane of a lung
      adenocarcinoma cell line and in the cell cytoplasm.
AB  - Lipocortin 1 (annexin I) is a calcium- and phospholipid-binding annexin protein
      which can be externalised from cells despite the lack of a signal sequence. To
      determine its cellular distribution lipocortin 1 in A549 human lung
      adenocarcinoma cells was localised by light- and electron-microscopic
      immunocytochemistry and by cell fractionation and western blotting. Lipocortin 1
      immunoreactivity is concentrated in prominent patches associated with the plasma
      membrane. The intensity of these patches varied with the confluence and duration
      of the culture and was not detectably diminished by an EDTA wash before fixation.
      Tubulin and cytokeratin 8 were colocalized with lipocortin 1 in the patches.
      Within the cells lipocortin 1 was distributed throughout the cytoplasm. Electron
      microscopy revealed prominent immunoreactivity along the plasma membrane with
      occasional large clusters of gold particles in contact with the membrane surface
      of the cells; within the cytoplasm the membrane of some vesicle/vacuole
      structures and some small electron-dense bodies was immunoreactive, but no
      immunogold particles were associated with the multilamellar bodies. Subcellular
      fractionation, extraction and western blotting showed that lipocortin 1 in the
      membrane pellet was present as two distinct fractions; one, intimately associated
      with the lipid bilayer, which behaved like an integral membrane protein and one
      loosely attached which behaved like a peripheral membrane protein. The results
      show that a substantial amounts of lipocortin 1 is concentrated in focal
      structures associated with and immediately beneath the plasma membrane. These
      might form part of the mechanism by which lipocortin 1 is released from the
      cells.

PMID- 9570759
TI  - Expression of specific tau exons in normal and tumoral pancreatic acinar cells.
AB  - Tau is a neuron-specific microtubule-associated protein (MAP) that is required
      for the development and maintaining neuronal cell polarity. Tau is encoded by a
      single gene, while its transcript undergoes a complex and regulated alternative
      splicing. We have recently reported that tau-like MAPs of 48-55 kDa,
      corresponding to 6 kb mRNA on northern blots, are expressed in pancreatic acinar
      cells. In the present study, the expression of tau exons in normal and tumoral
      pancreatic acinar cells was investigated by RT-PCR and cDNA sequencing. Tau
      isoforms with four tubulin-binding motifs containing either none, one or two N
      terminal inserts (exons 2, 3) are indiscriminately expressed in normal and
      tumoral cells. However, tau transcripts containing the sequence encoded by exon 6
      are specifically expressed in pancreatic tumoral cells from exocrine origin. By
      immunofluorescence and electron microscopy, we have identified in cellular
      extensions of tumoral cells, tau-decorated microtubules arranged in bundles like
      those found in neuronal processes. Tau antisense oligonucleotides inhibit the
      development of these cellular processes and the expression of the 55 kDa tau
      isoform.

PMID- 9570760
TI  - Sequential silver staining and in situ hybridization reveal a direct association
      between rDNA levels and the expression of homologous nucleolar organizing
      regions: a hypothesis for NOR structure and function.
AB  - We have developed a procedure for sequential silver staining and in situ
      hybridization to analyze the relationship between the amount of rDNA present in
      nucleolar organizer regions, as estimated by in situ hybridization, and their
      level of expression, as estimated by the silver signal. For simplicity we used
      cells from the insectivorous mole Talpa occidentalis, which have a single pair of
      nucleolar organizer regions in chromosome pair 3. The relative content of
      ribosomal cistrons was also related to the hierarchy of activation of the
      nucleolar organizer regions present in this chromosomal pair. Statistical
      analyses demonstrated that both the relative level of expression and the
      activation hierarchy depended mainly on the number of ribosomal cistrons in
      nucleolar organizer regions. We propose a functional two-step hypothesis, which
      is consistent with most known data concerning interchromosomal, intercellular and
      interindividual variation in a number of plant and animal species, including
      Talpa occidentalis. In step one, the first available transcription factors bind
      randomly to the ribosomal promoters, such that larger nucleolar organizer regions
      are more likely to recruit them. In the second step the remaining transcription
      factors are recruited in a cooperative way, thus completing activation of one
      nucleolar organizer region, before the next one becomes active.

PMID- 9570761
TI  - LBR, a chromatin and lamin binding protein from the inner nuclear membrane, is
      proteolyzed at late stages of apoptosis.
AB  - Chromatin condensation and apposition to the nuclear envelope is an important
      feature of the execution phase of apoptosis. During this process, lamin proteins
      that are located between the inner nuclear membrane and heterochromatin are
      proteolyzed by the apoptosis-specific protease caspase 6. We have investigated
      the fate of nuclear membranes during apoptosis by studying the lamin B receptor
      (LBR), a transmembrane protein of the inner nuclear membrane. LBR interacts
      through its nucleoplasmic amino-terminal domain with both heterochromatin and B
      type lamins, and is phosphorylated throughout the cell cycle, but on different
      sites in interphase and mitosis. We report here that: (i) the amino-terminal
      domain of LBR is specifically cleaved during apoptosis to generate an
      approximately 20 kDa soluble fragment; (ii) the cleavage of LBR is a late event
      of apoptosis and occurs subsequent to lamin B cleavage; (iii) the phosphorylation
      of LBR during apoptosis is similar to that occurring in interphase. As the
      association of condensed chromatin with the inner nuclear membrane persists until
      the late stages of apoptosis, we suggest that the chromatin binding protein LBR
      plays a major role in maintaining this association.

PMID- 9570763
TI  - The SELF-PRUNING gene of tomato regulates vegetative to reproductive switching of
      sympodial meristems and is the ortholog of CEN and TFL1.
AB  - Vegetative and reproductive phases alternate regularly during sympodial growth in
      tomato. In wild-type 'indeterminate' plants, inflorescences are separated by
      three vegetative nodes. In 'determinate' plants homozygous for the recessive
      allele of the SELF-PRUNING (SP) gene, sympodial segments develop progressively
      fewer nodes until the shoot is terminated by two consecutive inflorescences. We
      show here that the SP gene is the tomato ortholog of CENTRORADIALIS and TERMINAL
      FLOWER1, genes which maintain the indeterminate state of inflorescence meristems
      in Antirrhinum and Arabidopsis respectively. The sp mutation results in a single
      amino acid change (P76L), and the mutant phenotype is mimicked by overexpressing
      the SP antisense RNA. Ectopic and overexpression of the SP and CEN transgenes in
      tomato rescues the 'indeterminate' phenotype, conditions the replacement of
      flowers by leaves in the inflorescence and suppresses the transition of the
      vegetative apex to a reproductive shoot. The SELF-PRUNING gene is expressed in
      shoot apices and leaves from very early stages, and later in inflorescence and
      floral primordia as well. This expression pattern is similar to that displayed by
      the tomato ortholog LEAFY and FLORICAULA. Comparison of the sympodial, day
      neutral shoot system of tomato and the monopodial, photoperiod-sensitive systems
      of Arabidopsis and Antirrhinum suggests that flowering genes that are required
      for the processing of floral induction signals in Arabidopsis and Antirrhinum are
      required in tomato to regulate the alternation between vegetative and
      reproductive cycles in sympodial meristems.

PMID- 9570762
TI  - BIMAAPC3, a component of the Aspergillus anaphase promoting complex/cyclosome, is
      required for a G2 checkpoint blocking entry into mitosis in the absence of NIMA
      function.
AB  - Temperature sensitive (ts) nimA mutants of Aspergillus nidulans arrest at a
      unique point in G2 which is post activation of CDC2. Here we show that this G2
      arrest is due to loss of nimA function and that it is dependent on BIMAAPC3, a
      component of the anaphase promoting complex/cyclosome (APC/C). Whereas nimA
      single mutants arrested in G2 with decondensed chromatin and interphase
      microtubule arrays, nimA, bimAAPC3 double mutants arrested growth with condensed
      chromatin and aster-like microtubule arrays. nimA, bimAAPC3 double mutants
      entered mitosis with kinetics similar to bimAAPC3 single mutants and wild-type
      cells, indicating a checkpoint-like role for BIMAAPC3 in G2. Even cells which had
      been depleted for NIMA protein and which contained insignificant levels of NIMA
      kinase activity entered mitosis on inactivation of bimAAPC3. BIMAAPC3 was present
      in a >25S complex containing BIMEAPC1, and bimAAPC3 mutants were sensitive to
      elevated CYCLIN B expression, consistent with BIMAAPC3 being a component of the
      APC/C. Inactivation of bimAAPC3 had little affect on the steady state levels of
      the B-type cyclin, NIMECyclin B. Our results indicate that BIMAAPC3, and most
      likely the APC/C itself, is activated in G2 in nimA mutants. We propose that
      APC/C activation is part of a novel, late G2 checkpoint, which responds to a
      defective process or structure in nimA mutants, and which prevents inappropriate
      entry into mitosis.

PMID- 9570764
TI  - Expression of the murine Hoxa4 gene requires both autoregulation and a conserved
      retinoic acid response element.
AB  - Analysis of the regulatory regions of the Hox genes has revealed a complex array
      of positive and negative cis-acting elements that control the spatial and
      temporal pattern of expression of these genes during embryogenesis. In this study
      we show that normal expression of the murine Hoxa4 gene during development
      requires both autoregulatory and retinoic acid-dependent modes of regulation.
      When introduced into a Hoxa4 null background, expression of a lacZ reporter gene
      driven by the Hoxa4 regulatory region (Hoxa4/lacZ) is either abolished or
      significantly reduced in all tissues at E10. 5-E12.5. Thus, the observed
      autoregulation of the Drosophila Deformed gene is conserved in a mouse homolog in
      vivo, and is reflected in a widespread requirement for positive feedback to
      maintain Hoxa4 expression. We also identify three potential retinoic acid
      response elements in the Hoxa4 5' flanking region, one of which is identical to a
      well-characterized element flanking the Hoxd4 gene. Administration of retinoic
      acid to Hoxa4/lacZ transgenic embryos resulted in stage-dependent ectopic
      expression of the reporter gene in the neural tube and hindbrain. When
      administered to Hoxa4 null embryos, however, persistent ectopic expression was
      not observed, suggesting that autoregulation is required for maintenance of the
      retinoic acid-induced expression. Finally, mutation of the consensus retinoic
      acid response element eliminated the response of the reporter gene to exogenous
      retinoic acid, and abolished all embryonic expression in untreated embryos, with
      the exception of the neural tube and prevertebrae. These data add to the evidence
      that Hox gene expression is regulated, in part, by endogenous retinoids and
      autoregulatory loops.

PMID- 9570765
TI  - Position dependent control of cell fate in the Fucus embryo: role of
      intercellular communication.
AB  - The early embryo of the brown alga Fucus comprises two cell types, i. e. rhizoid
      and thallus which are morphogically and cytologically distinguishable. Previous
      work has pointed to the cell wall as a source of position-dependent information
      required for polarisation and fate determination in the zygote and 2-celled
      embryo. In this study we have analysed the mechanism(s) of cell fate control and
      pattern formation at later embryonic stages using a combination of laser
      microsurgery and microinjection. The results indicate that the cell wall is
      required for maintenance of pre-existing polarity in isolated intact cells.
      However, all cell types ultimately have the capacity to re-differentiate or
      regenerate rhizoid cells in response to ablation of neighbouring cells. This
      regeneration is regulated in a position-dependent manner and is strongly
      influenced by intercellular communication, probably involving transport or
      diffusion of inhibitory signals which appear to be essential for regulation of
      cell fate decisions. This type of cell-to-cell communication does not involve
      symplastic transport or direct cell-cell contact inhibition. Apoplastic
      diffusible gradients appear to be involved in pattern formation in the
      multicellular embryo.

PMID- 9570766
TI  - Ecdysteroids govern two phases of eye development during metamorphosis of the
      moth, Manduca sexta.
AB  - The eye primordium of the moth, Manduca sexta, shows two different developmental
      responses to ecdysteroids depending on the concentration to which it is exposed.
      Tonic exposure to moderate levels of 20-hydroxyecdysone (20E) or its precursor,
      ecdysone, are required for progression of the morphogenetic furrow across the
      primordium. Proliferation, cell-type specification and organization of immature
      ommatidial clusters occur in conjunction with furrow progression. These events
      can be reversibly started or stopped in cultured primordia simply by adjusting
      levels of ecdysteroid to be above or below a critical threshold concentration. In
      contrast, high levels of 20E cause maturation of the photoreceptors and the
      support cells that comprise the ommatidia. Ommatidial maturation normally occurs
      after the furrow has crossed the primordium, but premature exposure to high
      levels of 20E at any time causes precocious maturation. In such cases, the furrow
      arrests irreversibly and cells behind the furrow produce a well-formed, but
      miniature, eye. Precocious and catastrophic metamorphosis occurs throughout such
      animals, suggesting that ecdysteroids control development of other tissues in a
      manner similar to the eye. The threshold concentrations of 20E required for
      furrow progression versus ommatidial maturation differ by about 17-fold. This
      capacity to regulate distinct phases of development by different concentrations
      of a single hormone is probably achieved by differential sensitivity of target
      gene promoters to induction by the hormone-bound receptor(s).

PMID- 9570767
TI  - Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic
      lineages.
AB  - In vertebrates, the medial moieties of the somites give rise to the vertebrae and
      epaxial muscles, which develop in close relationship with the axial organs,
      neural tube and notochord. The lateral moieties contribute to the ribs and to
      limb and body wall muscles (hypaxial muscles) after a phase of lateral and
      ventral migration. Surgical ablation of the neural tube and notochord in the
      chick embryo during segmentation and early differentiation of the somites (day 2
      of incubation) does not affect primary development of the hypaxial muscles, but
      leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell
      death in the somites. Here we demonstrate that cell death, which occurs within 24
      hours of excision of the axial organs, affects both myogenic and chondrogenic
      cell lineages defined, respectively, by the expression of MyoD and Pax-1 genes.
      In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial
      muscles, are preserved in the excised embryos. Backgrafting either the ventral
      neural tube or the notochord allows survival of MyoD- and Pax-1-expressing cells.
      Similarly, Sonic hedgehog-producing cells grafted in place of axial organs also
      rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles,
      ribs and vertebrae to undergo organogenesis. These results demonstrate that the
      ventral neural tube and the notochord promote the survival of both myogenic and
      chondrogenic cell lineages in the somites and that this action is mediated by
      Sonic hedgehog.

PMID- 9570768
TI  - Cell proliferation control by Notch signaling in Drosophila development.
AB  - The Notch receptor mediates cell interactions controlling the developmental fate
      of a broad spectrum of undifferentiated cells. By modulating Notch signaling in
      specific precursor cells during Drosophila imaginal disc development, we
      demonstrate that Notch activity can influence cell proliferation. The activation
      of the Notch receptor in the wing disc induces the expression of the wing margin
      patterning genes vestigial and wingless, and strong mitotic activity. However,
      the effect of Notch signaling on cell proliferation is not the simple consequence
      of the upregulation of either vestigial or wingless. Vestigial and Wingless, on
      the contrary, display synergistic effects with Notch signaling, resulting in the
      stimulation of cell proliferation in imaginal discs.

PMID- 9570769
TI  - Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus
      embryo and interacts with the Notch pathway.
AB  - The presomitic mesoderm of vertebrates undergoes a process of segmentation in
      which cell-cell interactions mediated by the Notch family of receptors and their
      associated ligands are involved. The vertebrate homologues of Drosophila &Dgr ;
      are expressed in a dynamic, segmental pattern within the presomitic mesoderm, and
      alterations in the function of these genes leads to a perturbed pattern of somite
      segmentation. In this study we have characterised Thylacine 1 which encodes a
      basic helix-loop-helix class transcription activator. Expression of Thylacine is
      restricted to the presomitic mesoderm, localising to the anterior half of several
      somitomeres in register with domains of X-Delta-2 expression. Ectopic expression
      of Thylacine in embryos causes segmentation defects similar to those seen in
      embryos in which Notch signalling is altered, and these embryos also show severe
      disruption in the expression patterns of the marker genes X-Delta-2 and X-ESR5
      within the presomitic mesoderm. Finally, the expression of Thylacine is altered
      in embryos when Notch signalling is perturbed. These observations suggest
      strongly that Thylacine 1 has a role in the segmentation pathway of the Xenopus
      embryo, by interacting with the Notch signalling pathway.

PMID- 9570770
TI  - Drosophila EcR-B ecdysone receptor isoforms are required for larval molting and
      for neuron remodeling during metamorphosis.
AB  - During the metamorphic reorganization of the insect central nervous system, the
      steroid hormone 20-hydroxyecdysone induces a wide spectrum of cellular responses
      including neuronal proliferation, maturation, cell death and the remodeling of
      larval neurons into their adult forms. In Drosophila, expression of specific
      ecdysone receptor (EcR) isoforms has been correlated with particular responses,
      suggesting that different EcR isoforms may govern distinct steroid-induced
      responses in these cells. We have used imprecise excision of a P element to
      create EcR deletion mutants that remove the EcR-B promoter and therefore should
      lack EcR-B1 and EcR-B2 expression but retain EcR-A expression. Most of these EcR
      B mutant animals show defects in larval molting, arresting at the boundaries
      between the three larval stages, while a smaller percentage of EcR-B mutants
      survive into the early stages of metamorphosis. Remodeling of larval neurons at
      metamorphosis begins with the pruning back of larval-specific dendrites and
      occurs as these cells are expressing high levels of EcR-B1 and little EcR-A. This
      pruning response is blocked in the EcR-B mutants despite the fact that adult
      specific neurons, which normally express only EcR-A, can progress in their
      development. These observations support the hypothesis that different EcR
      isoforms control cell-type-specific responses during remodeling of the nervous
      system at metamorphosis.

PMID- 9570771
TI  - Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain
      encoding genes, suggests a role in mammalian head development.
AB  - LIM-homeobox containing (Lhx) genes encode trascriptional regulators which play
      critical roles in a variety of developmental processes. We have identified two
      genes belonging to a novel subfamily of mammalian Lhx genes, designated Lhx6 and
      Lhx7. Whole-mount in situ hybridisation showed that Lhx6 and Lhx7 were expressed
      during mouse embryogenesis in overlapping domains of the first branchial arch and
      the basal forebrain. More specifically, expression of Lhx6 and Lhx7 was detected
      prior to initiation of tooth formation in the presumptive oral and odontogenic
      mesenchyme of the maxillary and mandibular processes. During tooth formation,
      expression was restricted to the mesenchyme of individual teeth. Using explant
      cultures, we have shown that expression of Lhx6 and Lhx7 in mandibular mesenchyme
      was under the control of signals derived from the overlying epithelium; such
      signals were absent from the epithelium of the non-odontogenic second branchial
      arch. Furthermore, expression studies and bead implantation experiments in vitro
      have provided strong evidence that Fgf8 is primarily responsible for the
      restricted expression of Lhx6 and Lhx7 in the oral aspect of the maxillary and
      mandibular processes. In the telencephalon, expression of both genes was
      predominantly localised in the developing medial ganglionic eminences, flanking a
      Fgf8-positive midline region. We suggest that Fgf8 and Lhx6 and Lhx7 are key
      components of signalling cascades which determine morphogenesis and
      differentiation in the first branchial arch and the basal forebrain.

PMID- 9570772
TI  - Signalling by the Drosophila epidermal growth factor receptor is required for the
      specification and diversification of embryonic muscle progenitors.
AB  - Muscle development initiates in the Drosophila embryo with the segregation of
      single progenitor cells, from which a complete set of myofibres arises. Each
      progenitor is assigned a unique fate, characterized by the expression of
      particular identity genes. We now demonstrate that the Drosophila epidermal
      growth factor receptor provides an inductive signal for the specification of a
      large subset of muscle progenitors. In the absence of the receptor or its ligand,
      SPITZ, specific progenitors fail to segregate. The resulting unspecified
      mesodermal cells undergo programmed cell death. In contrast, receptor
      hyperactivation generates supernumerary progenitors, as well as the duplication
      of at least one SPITZ-dependent myofibre. The development of individual muscles
      is differentially sensitive to variations in the level of signalling by the
      epidermal growth factor receptor. Such graded myogenic effects can be influenced
      by alterations in the functions of Star and rhomboid. In addition, muscle
      patterning is dependent on the generation of a spatially restricted, activating
      SPITZ signal, a process that may rely on the localized mesodermal expression of
      RHOMBOID. Thus, the epidermal growth factor receptor contributes both to muscle
      progenitor specification and to the diversification of muscle identities.

PMID- 9570773
TI  - sma-1 encodes a betaH-spectrin homolog required for Caenorhabditis elegans
      morphogenesis.
AB  - Morphogenesis transforms the C. elegans embryo from a ball of cells into a
      vermiform larva. During this transformation, the embryo increases fourfold in
      length; present data indicates this elongation results from contraction of the
      epidermal actin cytoskeleton. In sma-1 mutants, the extent of embryonic
      elongation is decreased and the resulting sma-1 larvae, although viable, are
      shorter than normal. We find that sma-1 mutants elongate for the same length of
      time as wild-type embryos, but at a decreased rate. The sma-1 mutants we have
      isolated vary in phenotypic severity, with the most severe alleles showing the
      greatest decrease in elongation rate. The sma-1 gene encodes a homolog of betaH
      spectrin, a novel beta-spectrin isoform first identified in Drosophila. sma-1 RNA
      is expressed in epithelial tissues in the C. elegans embryo: in the embryonic
      epidermis at the start of morphogenesis and subsequently in the developing
      pharynx, intestine and excretory cell. In Drosophila, betaH-spectrin associates
      with the apical plasma membrane of epithelial cells; beta-spectrin is found at
      the lateral membrane. We propose that SMA-1 is a component of an apical membrane
      skeleton in the C. elegans embryonic epidermis that determines the rate of
      elongation during morphogenesis.

PMID- 9570774
TI  - Expression of the Emx-1 and Dlx-1 homeobox genes define three molecularly
      distinct domains in the telencephalon of mouse, chick, turtle and frog embryos:
      implications for the evolution of telencephalic subdivisions in amniotes.
AB  - Homologies between vertebrate forebrain subdivisions are still uncertain. In
      particular the identification of homologs of the mammalian neocortex or the
      dorsal ventricular ridge (DVR) of birds and reptiles is still a matter of
      dispute. To get insight about the organization of the primordia of the main
      telencephalic subdivisions along the anteroposterior axis of the neural tube, a
      fate map of the dorsal prosencephalon was obtained in avian chimeras at the 8- to
      9-somite stage. At this stage, the primordia of the pallium, DVR and striatum
      were located on the dorsal aspect of the prosencephalon and ordered
      caudorostrally along the longitudinal axis of the brain. Expression of homeobox
      containing genes of the Emx, Dlx and Pax families were used as markers of
      anteroposterior developmental subdivisions of the forebrain in mouse, chick,
      turtle and frog. Their expression domains delineated three main telencephalic
      subdivisions in all species at the onset of neurogenesis: the pallial,
      intermediate and striatal neuroepithelial domains. The fate of the intermediate
      subdivisions diverged, however, between species at later stages of development.
      Homologies between forebrain subdivisions are proposed based on the conservation
      and divergence of these gene expression patterns.

PMID- 9570775
TI  - Determination of sclerotome to the cartilage fate.
AB  - When the somite first forms the cells appear to be equivalent in potential. In
      order to understand the lineage diversification of the somite, the determination
      of sclerotome cells to the cartilage fate was tested using an in vivo challenge
      assay in which quail sclerotome fragments were grafted into a dorsal position in
      a chick host. Grafts containing undetermined cells were expected to differentiate
      into other tissues while grafts containing determined chondrocyte precursors were
      expected to consistently give rise to cartilage. We found that grafted sclerotome
      fragments from somite stages V-XX were capable of giving rise to integrated
      muscle and dermis and that it was not until fragments from stage XII somites were
      grafted that cartilage was consistently produced in the assay. Sclerotomal tissue
      from embryonic day 4-6 embryos remained as morphologically unintegrated
      mesenchyme when grafted into an embryonic day 2 host, but formed only cartilage
      when placed into an identically aged host. Vertebral body cartilage from
      embryonic day 7 and embryonic day 8 embryos formed exclusively ectopic cartilage
      in an embryonic day 2 host. We conclude that cells determined to the cartilage
      fate do not appear until somite stage XII, but that not all sclerotome cells are
      determined at this time. The effect of host age on the differentiation and
      morphogenetic behavior of sclerotome fragment grafts in this assay indicate the
      existence of developmental eras within the embryo.

PMID- 9570776
TI  - Drosophila betaHeavy-spectrin is essential for development and contributes to
      specific cell fates in the eye.
AB  - The spectrin membrane skeleton is a ubiquitous cytoskeletal structure with
      several cellular roles, including the maintenance of cell integrity,
      determination of cell shape and as a contributor to cell polarity. We have
      isolated mutations in the gene encoding &bgr ;Heavy-spectrin in Drosophila, and
      have named this essential locus karst. karst mutant individuals have a
      pleiotropic phenotype characterized by extensive larval lethality and, in adult
      escapers, rough eyes, bent wings, tracheal defects and infertility. Within karst
      mutant eyes, a significant number of ommatidia specifically lack photoreceptor R7
      alongside more complex morphological defects. Immunolocalization of betaHeavy
      spectrin in wild-type eye-antennal and wing imaginal discs reveals that betaHeavy
      spectrin is present in a restricted subdomain of the membrane skeleton that
      colocalizes with DE-cadherin. We propose a model where normal levels of Sevenless
      signaling are dependent on tight cell-cell adhesion facilitated by the betaHeavy
      spectrin membrane skeleton. Immunolocalization of betaHeavy-spectrin in the adult
      and larval midgut indicates that it is a terminal web protein, but we see no
      gross morphological defects in the adult apical brush border in karst mutant
      flies. Rhodamine phalloidin staining of karst mutant ovaries similarly reveals no
      conspicuous defect in the actin cytoskeleton or cellular morphology in egg
      chambers. This is in contrast to mutations in alpha-spectrin, the molecular
      partner of betaHeavy-spectrin, which affect cellular structure in both the larval
      gut and adult ovaries. Our results emphasize the fundamental contribution of the
      spectrin membrane skeleton to normal development and reveals a critical interplay
      between the integrity of a cell's membrane skeleton, the structure of cell-cell
      contacts and cell signaling.

PMID- 9570777
TI  - Dystonin is an essential component of the Schwann cell cytoskeleton at the time
      of myelination.
AB  - A central role for the Schwann cell cytoskeleton in the process of peripheral
      nerve myelination has long been suggested. However, there is no genetic or
      biological evidence as yet to support this assumption. Here we show that dystonia
      musculorum (dt) mice, which carry mutations in dystonin, a cytoskeletal
      crosslinker protein, have hypo/amyelinated peripheral nerves. In neonatal dt
      mice, Schwann cells were arrested at the promyelinating stage and had multiple
      myelinating lips. Nerve graft experiments and primary cultures of Schwann cells
      demonstrated that the myelination abnormality in dt mice was autonomous to
      Schwann cells. In culture, dt Schwann cells showed abnormal polarization and
      matrix attachment, and had a disorganized cytoskeleton. Finally, we show that the
      dt mutation was semi-dominant, heterozygous animals presenting hypo- and hyper
      myelinated peripheral nerves. Altogether, our results suggest that dt Schwann
      cells are deficient for basement membrane interaction and demonstrate that
      dystonin is an essential component of the Schwann cell cytoskeleton at the time
      of myelination.

PMID- 9570778
TI  - Environmental control of the cell cycle in Drosophila: nutrition activates
      mitotic and endoreplicative cells by distinct mechanisms.
AB  - In newly hatched Drosophila larvae, quiescent cells reenter the cell cycle in
      response to dietary amino acids. To understand this process, we varied larval
      nutrition and monitored effects on cell cycle initiation and maintenance in the
      mitotic neuroblasts and imaginal disc cells, as well as the endoreplicating cells
      in other larval tissues. After cell cycle activation, mitotic and endoreplicating
      cells respond differently to the withdrawal of nutrition: mitotic cells continue
      to proliferate in a nutrition-independent manner, while most endoreplicating
      cells reenter a quiescent state. We also show that ectopic expression of
      Drosophila Cyclin E or the E2F transcription factor can drive quiescent
      endoreplicating cells, but not quiescent imaginal neuroblasts, into S-phase.
      Conversely, we demonstrate that quiescent imaginal neuroblasts, but not quiescent
      endoreplicating cells, can be induced to enter the cell cycle when co-cultured
      with larval fat body in vitro. These results demonstrate a fundamental difference
      in the control of cell cycle activation and maintenance in these two cell types,
      and imply the existence of a novel mitogen generated by the larval fat body in
      response to nutrition.

PMID- 9570779
TI  - The Dorsal-related immunity factor (Dif) can define the dorsal-ventral axis of
      polarity in the Drosophila embryo.
AB  - In Drosophila embryos, dorsal-ventral polarity is defined by a signal
      transduction pathway that regulates nuclear import of the Dorsal protein. Dorsal
      protein's ability to act as a transcriptional activator of some zygotic genes and
      a repressor of others defines structure along the dorsal-ventral axis. Dorsal is
      a member of a group of proteins, the Rel-homologous proteins, whose activity is
      regulated at the level of nuclear localization. Dif, a more recently identified
      Drosophila Rel-homologue, has been proposed to act as a mediator of the immune
      response in Drosophila. In an effort to understand the function and regulation of
      Rel-homologous proteins in Drosophila, we have expressed Dif protein in
      Drosophila embryos derived from dorsal mutant mothers. We found that the Dif
      protein was capable of restoring embryonic dorsal-ventral pattern elements and
      was able to define polarity correctly with respect to the orientation of the egg
      shell. This, together with the observation that the ability of Dif to restore a
      dorsal-ventral axis depended on the signal transduction pathway that normally
      regulates Dorsal, suggests that Dif protein formed a nuclear concentration
      gradient similar to that seen for Dorsal. By studying the expression of Dorsal
      target genes we found that Dif could activate the zygotic genes that Dorsal
      activates and repress the genes repressed by Dorsal. Differences in the
      expression of these target genes, as well as the results from interaction studies
      carried out in yeast, suggest that Dif is not capable of synergizing with the
      basic helix-loop-helix transcription factors with which Dorsal normally
      interacts, and thereby lacks an important component of Dorsal-mediated pattern
      formation.

PMID- 9570780
TI  - Galanin receptor-mediated inhibition of glutamate release in the arcuate nucleus
      of the hypothalamus.
AB  - It is thought that galanin, a 29 amino acid neuropeptide, is involved in various
      neuronal functions, including the regulation of food intake and hormone release.
      Consistent with this idea, galanin receptors have been demonstrated throughout
      the brain, with high levels being observed in the hypothalamus. However, little
      is known about the mechanisms by which galanin elicits its actions in the brain.
      Therefore, we studied the effects of galanin and its analogs on synaptic
      transmission using an in vitro slice preparation of rat hypothalamus. In arcuate
      nucleus neurons, application of galanin resulted in an inhibition of evoked
      glutamatergic EPSCs and a decrease in paired-pulse depression, indicating a
      presynaptic action. The fragments galanin 1-16 and 1-15 produced a robust
      depression of synaptic transmission, whereas the fragment 3-29 produced a lesser
      degree of depression. The chimeric peptides C7, M15, M32, and M40, which have
      been reported to antagonize some actions of galanin, all produced varying degrees
      of depression of evoked EPSCs. In a minority of cases, C7, M15, and M40
      antagonized the actions of galanin. Analysis of mEPSCs in the presence of TTX and
      Cd2+, or after application of alpha-latrotoxin, indicated a site of action for
      galanin downstream of Ca2+ entry. Thus, our data suggest that galanin acts via
      several subtypes of presynaptic receptors to depress synaptic transmission in the
      rat arcuate nucleus.

PMID- 9570781
TI  - Determinants of voltage attenuation in neocortical pyramidal neuron dendrites.
AB  - How effectively synaptic and regenerative potentials propagate within neurons
      depends critically on the membrane properties and intracellular resistivity of
      the dendritic tree. These properties therefore are important determinants of
      neuronal function. Here we use simultaneous whole-cell patch-pipette recordings
      from the soma and apical dendrite of neocortical layer 5 pyramidal neurons to
      directly measure voltage attenuation in cortical neurons. When combined with
      morphologically realistic compartmental models of the same cells, the data
      suggest that the intracellular resistivity of neocortical pyramidal neurons is
      relatively low ( approximately 70 to 100 Omegacm), but that voltage attenuation
      is substantial because of nonuniformly distributed resting conductances present
      at a higher density in the distal apical dendrites. These conductances, which
      were largely blocked by bath application of CsCl (5 mM), significantly increased
      steady-state voltage attenuation and decreased EPSP integral and peak in a manner
      that depended on the location of the synapse. Together these findings suggest
      that nonuniformly distributed Cs-sensitive and -insensitive resting conductances
      generate a "leaky" apical dendrite, which differentially influences the
      integration of spatially segregated synaptic inputs.

PMID- 9570782
TI  - Functional analysis of the C2A domain of synaptotagmin 1: implications for
      calcium-regulated secretion.
AB  - Synaptotagmin 1 is proposed to function as a low affinity calcium sensor for
      calcium-triggered exocytosis from neural and neuroendocrine cells. Because of the
      calcium-binding properties of the C2A domain of synaptotagmin 1, calcium
      dependent interactions through this domain may modulate neurotransmitter release.
      We addressed this question by using alanine-scanning mutagenesis to generate a
      series of mutations within the C2A domain of synaptotagmin 1. The effects of
      these mutations on synaptotagmin 1 C2A function were analyzed for (1) calcium
      dependent phospholipid binding, (2) calcium-dependent binding to syntaxin 1A, a
      plasma membrane protein critical for vesicle docking or fusion, and (3) calcium
      regulated secretion after microinjection into neuroendocrine pheochromocytoma
      (PC12) cells. Our analyses reveal that a polylysine motif at residues 189-192
      confers an inhibitory effect on secretion by recombinant synaptotagmin C2A
      fragments. The synaptotagmin 1 C2A polylysine motif functions independently of
      calcium-mediated interactions with phospholipids and syntaxin 1A. Furthermore,
      alpha-latrotoxin reverses the inhibitory effect of injected recombinant C2A
      fragments, suggesting that they perturb the cellular calcium-sensing machinery by
      interfering with synaptotagmin 1 activity in vivo. Our results indicate that
      novel calcium-independent interactions mediated through the C2A polylysine motif
      of synaptotagmin 1 function to modulate neurotransmitter release.

PMID- 9570783
TI  - Downregulation of transient K+ channels in dendrites of hippocampal CA1 pyramidal
      neurons by activation of PKA and PKC.
AB  - We have reported recently a high density of transient A-type K+ channels located
      in the distal dendrites of CA1 hippocampal pyramidal neurons and shown that these
      channels shape EPSPs, limit the back-propagation of action potentials, and
      prevent dendritic action potential initiation (). Because of the importance of
      these channels in dendritic signal propagation, their modulation by protein
      kinases would be of significant interest. We investigated the effects of
      activators of cAMP-dependent protein kinase (PKA) and the Ca2+-dependent
      phospholipid-sensitive protein kinase (PKC) on K+ channels in cell-attached
      patches from the distal dendrites of hippocampal CA1 pyramidal neurons. Inclusion
      of the membrane-permeant PKA activators 8-bromo-cAMP (8-br-cAMP) or forskolin in
      the dendritic patch pipette resulted in a depolarizing shift in the activation
      curve for the transient channels of approximately 15 mV. Activation of PKC by
      either of two phorbol esters also resulted in a 15 mV depolarizing shift of the
      activation curve. Neither PKA nor PKC activation affected the sustained or slowly
      inactivating component of the total outward current. This downregulation of
      transient K+ channels in the distal dendrites may be responsible for some of the
      frequently reported increases in cell excitability found after PKA and PKC
      activation. In support of this hypothesis, we found that activation of either PKA
      or PKC significantly increased the amplitude of back-propagating action
      potentials in distal dendrites.

PMID- 9570784
TI  - Morphine administered in the substantia gelatinosa of the spinal trigeminal
      nucleus caudalis inhibits nociceptive activities in the spinal trigeminal nucleus
      oralis.
AB  - The present study investigates the effects of morphine microinjection into the
      spinal trigeminal nucleus caudalis (Sp5C) or the spinal trigeminal nucleus oralis
      (Sp5O) on C-fiber-evoked activities of Sp5O convergent neurons, after
      supramaximal percutaneous electrical stimulation in halothane-anesthetized rats.
      When it was microinjected into the Sp5O, morphine (2.5 microg in 0. 25 microl)
      never depressed the C-fiber-evoked responses of Sp5O convergent neurons (n = 13),
      whereas these neurons were responsive to the inhibitory effects of systemic
      morphine (6 mg/kg, i.v.) in a naloxone-reversible manner. On the contrary,
      morphine microinjected into the Sp5C produced a naloxone-reversible inhibition of
      the C-fiber-evoked responses of Sp5O neurons (n = 14). The magnitude and the time
      course of this effect varied according to the location of the injection sites.
      After microinjection into the superficial laminae (n = 7), a strong depressive
      effect of morphine (7 +/- 5% of control) on the C-fiber-evoked responses was
      apparent as soon as 5 min after the injection and could always be reversed by
      naloxone, administered either intravenously (0.4 mg/kg) or locally (2.5 microg in
      0.6 microl) at the same site as morphine. After microinjection into deeper
      laminae (V-VI), a significant depressive effect (34 +/- 5% of control) of
      morphine could be detected only 20 min after the injection and was reversed only
      by intravenous administration of naloxone. These results suggest that morphine
      exerts its antinociceptive action on Sp5O convergent neurons by blocking the C
      fiber inputs that relay in the Sp5C substantia gelatinosa. The mechanisms that
      underlie the activation of Sp5O convergent neurons by C-fibers and the inhibition
      of C-fiber-evoked responses of Sp5O convergent neurons by morphine microinjected
      into the Sp5C are discussed.

PMID- 9570785
TI  - The weaver mutation causes a loss of inward rectifier current regulation in
      premigratory granule cells of the mouse cerebellum.
AB  - Considerable interest has recently focused on the weaver mutation, which causes
      inward rectifier channel alterations leading to profound impairment of neuronal
      differentiation and to severe motor dysfunction in mice (Hess, 1996). The
      principal targets of mutation are cerebellar granule cells, most of which fail to
      differentiate and degenerate in a premigratory position (Rakic and Sidman,
      1973a,b). Two hypotheses have been put forward to explain the pathogenetic role
      of mutant inward rectifier channels: namely that inward rectifier channel
      activity is either lacking (Surmeier et al., 1996) or altered (Kofuji et al.,
      1996; Silverman et al., 1996; Slesinger et al., 1996). We have examined this
      question by recording inward rectifier currents from cerebellar granule cells in
      situ at different developmental stages in wild-type and weaver mutant mice. In
      wild-type mice, the inward rectifier current changed from a G-protein-dependent
      activation to a constitutive activation as granule cells developed from
      premigratory to postmigratory stages. In weaver mutant mice, G-protein-dependent
      inward rectifier currents were absent in premigratory granule cells. A population
      of putative granule cells in the postmigratory position expressed a constitutive
      inward rectifier current with properties compatible with mutated GIRK2 channels
      expressed in heterologous systems. Because granule cells degenerate at the
      premigratory stage (Smeyne and Goldowitz, 1989), the loss of inward rectifier
      current and its regulation of membrane potential are likely to play a key role in
      the pathogenesis of weaver neuronal degeneration.

PMID- 9570786
TI  - Extrasynaptic vesicular transmitter release from the somata of substantia nigra
      neurons in rat midbrain slices.
AB  - Substantia nigra neurons release dopamine from their somatodendritic regions. A
      long-unresolved question is whether this release occurs by exocytosis or by a
      nonvesicular mechanism. We used carbon fiber microelectrodes in a brainstem slice
      to assay secretion from single cell bodies that had been cleared of connective
      tissue. Amperometry at the carbon fiber microelectrodes revealed unitary events
      in approximately 90% of cells in resting conditions. These events had charge
      integrals ranging from a few femtocoulombs to several hundred femtocoulombs (fC).
      Local glutamate application enhanced the event frequency by 3.5-fold on average
      and up to 10-fold in highly responsive cells, although the mean charge integral
      was not modified. Local application of a high K+-containing saline had effects
      similar to those of glutamate. The frequency of resting and stimulated
      amperometric events was much lower at 21-22 degreesC than at 32-35 degreesC. The
      addition of Cd2+ (50 microM), a blocker of voltage-dependent Ca2+ channels, to
      the bath solution blocked the stimulatory effects of glutamate. These results
      suggest that dopamine is released from the somata of substantia nigra neurons by
      exocytosis and that this mechanism is regulated by neuronal electrical activity.
      More generally, this study demonstrates the applicability of carbon fiber
      microelectrodes to the measurement of quantal monoamine secretion in brain
      slices.

PMID- 9570787
TI  - Effects of glucose deprivation, chemical hypoxia, and simulated ischemia on Na+
      homeostasis in rat spinal cord astrocytes.
AB  - A steep inwardly directed Na+ gradient is essential for glial functions such as
      glutamate reuptake and regulation of intracellular ion concentrations. We
      investigated the effects of glucose deprivation, chemical hypoxia, and simulated
      ischemia on intracellular Na+ concentration ([Na+]i) in cultured spinal cord
      astrocytes using fluorescence ratio imaging with sodium-binding benzofuran
      isophthalate (SBFI) AM. Glucose removal or chemical hypoxia (induced by 10 mM
      NaN3) for 60 min increased [Na+]i from a baseline of 8.3 to 11 mM. Combined
      glycolytic and respiratory blockage by NaN3 and 0 glucose saline caused [Na+]i to
      increase by 20 mM, similar to the [Na+]i increases elicited by blocking the
      Na+/K+-ATPase with ouabain. Recovery from large [Na+]i increases (>15 mM) induced
      by the glutamatergic agonist kainate was attenuated during glucose deprivation or
      NaN3 application and was blocked in NaN3 and 0 glucose. To mimic in vivo
      ischemia, we exposed astrocytes to NaN3 and 0 glucose saline containing L-lactate
      and glutamate with increased [K+] and decreased [Na+], [Ca2+], and pH. This
      induced an [Na+]i decrease followed by an [Na+]i rise and a further [Na+]i
      increase after reperfusion with standard saline. Similar multiphasic [Na+]i
      changes were observed after NaN3 and 0 glucose saline with only reduced [Na+]e.
      Our results suggest that the ability to maintain a low [Na+]i enables spinal cord
      astrocytes to continue uptake of K+ and/or glutamate at the onset of energy
      failure. With prolonged energy failure, however, astrocytic [Na+]i rises; with
      loss of their steep transmembrane Na+ gradient, astrocytes may aggravate
      metabolic insults by carrier reversal and release of acid, K+, and/or glutamate
      into the extracellular space.

PMID- 9570788
TI  - Granule neuron regulation of Purkinje cell development: striking a balance
      between neurotrophin and glutamate signaling.
AB  - Granule neurons, presynaptic afferents of Purkinje cells, are potent regulators
      of Purkinje cell development. Purified Purkinje cells survive and differentiate
      poorly, whereas coculture with granule neurons enhances their survival and
      dendritic development. Here we investigate the role of neurotrophins in granule
      Purkinje cell interactions. BDNF or NT-4 improves, but NT-3 or CNTF reduces,
      survival of isolated Purkinje cells. When granule neurons are present, however,
      BDNF or NT-4 treatment leads to Purkinje cell loss. This decrease is overcome by
      anti-BDNF or TrkB-IgG-blocking reagents or by CNQX, a non-NMDA glutamate receptor
      antagonist. Furthermore, BDNF increases the spine density on the surviving
      Purkinje cells. These results suggest that Purkinje cell survival and
      differentiation are context-dependent and require a balance between neurotrophin-
      and activity-dependent signaling.

PMID- 9570789
TI  - Dendritic low-threshold calcium currents in thalamic relay cells.
AB  - The low-threshold calcium current (IT) underlies burst generation in
      thalamocortical (TC) relay cells and plays a central role in the genesis of
      synchronized oscillations by thalamic circuits. Here we have combined in vitro
      recordings and computational modeling techniques to investigate the consequences
      of dendritically located IT in TC cells. Simulations of a reconstructed TC cell
      were compared with the recordings obtained in the same cell to constrain the
      values of its passive parameters. T-current densities in soma and proximal
      dendrites were then estimated by matching the model to voltage-clamp recordings
      obtained in dissociated TC cells, which lack most of the dendrites. The distal
      dendritic T-current density was constrained by recordings in intact TC cells,
      which show 5-14 times larger peak T-current amplitudes compared with dissociated
      cells. Comparison of the model with the recordings of the same cell constrained
      further the T-current density in dendrites, which had to be 4.5-7.6 times higher
      than in the soma to reproduce all experimental results. Similar conclusions were
      reached using a simplified three-compartment model. Functionally, the model shows
      that the same amount of T-channels can lead to different bursting behaviors if
      they are exclusively somatic or distributed throughout the dendrites. In
      conclusion, this combination of models and experiments shows that dendritic T
      currents are necessary to reproduce low-threshold calcium electrogenesis in TC
      cells. Dendritic T-current may also have significant functional consequences,
      such as an efficient modulation of thalamic burst discharges by corticothalamic
      feedback.

PMID- 9570790
TI  - Evidence for involvement of the cGMP-protein kinase G signaling system in the
      induction of long-term depression, but not long-term potentiation, in the dentate
      gyrus in vitro.
AB  - The involvement of the cGMP-protein kinase G (PKG) signaling pathway in the
      induction of long-term depression (LTD) and long-term potentiation (LTP) was
      investigated in the medial perforant path of the dentate gyrus in vitro. Low
      frequency stimulation (LFS)-induced LTD of field EPSPs was inhibited by bath
      perfusion of the selective soluble guanylyl cyclase inhibitor 1H-[1,2,4]
      oxadiazolo[4,3, -a]quinoxalin-1-one (ODQ). LFS-induced LTD of EPSPs and whole
      cell patch-clamped EPSCs was also blocked by bath perfusion and postsynaptic
      intracellular injection, respectively, of the selective PKG inhibitor KT5823.
      Elevation of intracellular cGMP by perfusion of the cGMP phosphodiesterase
      inhibitor zaprinast resulted in induction of LTD of field EPSPs and EPSCs.
      Occlusion experiments showed mutual inhibition between LFS-induced LTD and
      zaprinast-induced LTD. The zaprinast-induced LTD of field EPSPs was inhibited by
      perfusion of ODQ and KT5823. In addition, zaprinast-induced LTD of EPSCs was
      inhibited by postsynaptic application of KT5823. Glutamate receptor stimulation,
      especially that of metabotropic glutamate receptors (mGluRs), was required for
      zaprinast-induced LTD, because cessation of test stimulation or perfusion with
      the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) inhibited
      zaprinast-induced LTD. No inhibitory effect of ODQ or KT5823 on the induction of
      LTP of EPSPs or EPSCs was found. These data indicate that the cGMP-guanyly
      cyclase-PKG signaling pathway in the dentate gyrus is essential for induction of
      LTD, although not of LTP, in the dentate gyrus.

PMID- 9570791
TI  - Region-specific and calcium-dependent increase in dialysate choline levels by
      NMDA.
AB  - NMDA receptor-induced excitotoxicity has been hypothesized to mediate abnormal
      choline (Cho) metabolism that is involved in alterations in membrane permeability
      and cell death in certain neurodegenerative disorders. To determine whether NMDA
      receptor overactivation modulates choline metabolism in vivo, we investigated the
      effects of NMDA on interstitial choline concentrations using microdialysis.
      Perfusion of NMDA by retrodialysis increased dialysate choline (approximately
      400%) and reduced dialysate acetylcholine (Ach) (approximately 40%). Choline
      levels remained increased for at least 2.5 hr, but acetylcholine returned to
      pretreatment values 75 min after NMDA perfusion. The NMDA-evoked increase in
      dialysate choline was calcium and concentration dependent and was prevented with
      1 mM AP-5, a competitive NMDA antagonist, but was not altered by mepacrine, a
      phospholipase A2 inhibitor. NMDA increased extracellular choline levels four- to
      fivefold in prefrontal cortex and hippocampus, produced a slight increase in
      neostriatum, and did not modify dialysate choline in cerebellum. Perfusion with
      NMDA for 2 hr produced a delayed, but not acute, reduction in choline
      acetyltransferase activity in the area surrounding the dialysis probe. Consistent
      with a lack of acute cholinergic neurotoxicity evoked by this treatment, basal
      acetylcholine levels were unaltered by 2 hr of continuous NMDA perfusion.
      Prolonged NMDA perfusion produced a 34% decrease in phosphatidylcholine content
      in the lipid fraction of the tissue surrounding the dialysis probe. These results
      show that NMDA modulates choline metabolism, eliciting a receptor-mediated,
      calcium-dependent, and region-specific increase in extracellular choline from
      membrane phospholipids that is not mediated by phospholipase A2 and precedes
      delayed excitotoxic neuronal cell death.

PMID- 9570792
TI  - The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate
      gated chloride channel concentrated near the synapse in parts of the dendritic
      membrane facing astroglia.
AB  - Antibodies to an excitatory amino acid transporter (EAAT4) label a glycoprotein
      of approximately 65 kDa strongly in the cerebellum and weakly in the forebrain.
      Cross-linking of cerebellar proteins with bis(sulfosuccinimidyl) suberate before
      solubilization causes dimer bands of EAAT4 and both dimer and trimer bands of the
      other glutamate transporters GLAST (EAAT1) and GLT (EAAT2) to appear on
      immunoblots. In contrast to GLAST, GLT, and EAAC (EAAT3), EAAT4 is unevenly
      distributed in the cerebellar molecular layer, being strongly expressed in
      parasagittal zones. It is located in cerebellar Purkinje cells, and the highest
      concentrations are seen in ones expressing high levels of zebrin II (aldolase C).
      The labeling of Purkinje cell spines and thin dendrites is stronger than that of
      large diameter dendrites and cell bodies. EAAT4 is present at low concentrations
      in the synaptic membrane, but is highly enriched in the parts of the dendritic
      and spine membranes facing astrocytes (which express GLAST and GLT) compared with
      parts facing neuronal membranes, suggesting a functional relationship with glial
      glutamate transporters. The presence of EAAT4 in intracellular cisterns and
      multivesicular organelles may reflect turnover of transporter in the plasma
      membrane. The total Purkinje cell spine surface and the EAAT4 concentration were
      found to be 1.1 m2/cm3 and 0.2 mg/cm3, respectively, in the molecular layer,
      corresponding to 1800 molecules/microm2. The juxtasynaptic location of EAAT4 may
      explain electrophysiological observations predicting the presence of a neuronal
      glutamate transporter near the release site at a Purkinje cell spine synapse.
      EAAT4 may function as a combined transporter and inhibitory glutamate receptor.

PMID- 9570793
TI  - Multiple routes to astrocytic differentiation in the CNS.
AB  - Ciliary neurotrophic factor (CNTF) acts instructively to switch multipotent stem
      cells of the CNS to an astrocytic fate. Here we show that CNTF causes activation
      of janus kinase-signal transducers and activators of transcription and mitogen
      activated protein kinase (MAPK) pathways with differential kinetics in these
      cells. Inhibition studies indicate that activation of the MAPK pathway is
      required early in the differentiation process, whereas activation of signal
      transducer and activator of transcription (STAT) proteins is required for
      commitment to an astrocytic fate. Bone morphogenetic proteins have also been
      shown to cause astrocytic differentiation but do not cause STAT activation or
      astrocytic differentiation in fibroblast growth factor 2-expanded fetal stem
      cells used here. These results show that there are two distinct routes to
      initiate astrocytic commitment in multipotent CNS precursors.

PMID- 9570794
TI  - Neurexophilins form a conserved family of neuropeptide-like glycoproteins.
AB  - Neurexophilin was discovered as a neuronal glycoprotein that is copurified with
      neurexin Ialpha during affinity chromatography on immobilized alpha-latrotoxin
      (Petrenko et al., 1996). We have now investigated how neurexophilin interacts
      with neurexins, whether it is post-translationally processed by site-specific
      cleavage similar to neuropeptides, and whether related neuropeptide-like proteins
      are expressed in brain. Our data show that mammalian brains contain four genes
      for neurexophilins the products of which share a common structure composed of
      five domains: an N-terminal signal peptide, a variable N-terminal domain, a
      highly conserved central domain that is N-glycosylated, a short linker region,
      and a conserved C-terminal domain that is cysteine-rich. When expressed in
      pheochromocytoma (PC12) cells with a replication-deficient adenovirus,
      neurexophilin 1 was rapidly N-glycosylated and then slowly processed to a smaller
      mature form, probably by endoproteolytic cleavage. Similar expression experiments
      in other neuron-like cells and in fibroblastic cells revealed that N
      glycosylation of neurexophilin 1 occurred in all cell types tested, whereas
      proteolytic processing was observed only in neuron-like cells. Finally, only
      recombinant neurexin Ialpha and IIIalpha but not neurexin Ibeta interacted with
      neurexophilin 1 and were preferentially bound to the processed mature form of
      neurexophilin. Together our data demonstrate that neurexophilins form a family of
      related glycoproteins that are proteolytically processed after synthesis and bind
      to alpha-neurexins. The structure and characteristics of neurexophilins indicate
      that they function as neuropeptides that may signal via alpha-neurexins.

PMID- 9570795
TI  - Defective motor behavior and neural gene expression in RIIbeta-protein kinase A
      mutant mice.
AB  - Motor behavior is modulated by dopamine-responsive neurons in the striatum, where
      dopaminergic signaling uses G-protein-coupled pathways, including those that
      result in the activation of cAMP-dependent protein kinase (PKA). The RIIbeta
      isoform of PKA is highly enriched in the striatum, and targeted disruption of the
      RIIbeta gene in mice leads to a dramatic reduction in total PKA activity in this
      region. Although the mutant mice show typical locomotor responses after acute
      administration of dopaminergic drugs, they display abnormalities in two
      experience-dependent locomotor behaviors: training on the rotarod task and
      locomotor sensitization to amphetamine. In addition, amphetamine induction of fos
      is absent, and the basal expression of dynorphin mRNA is reduced in the striatum.
      These results demonstrate that motor learning and the regulation of neuronal gene
      expression require RIIbeta PKA, whereas the acute locomotor effects of
      dopaminergic drugs are relatively unaffected by this PKA deficiency.

PMID- 9570796
TI  - A novel octopamine receptor with preferential expression in Drosophila mushroom
      bodies.
AB  - Octopamine is a neuromodulator that mediates diverse physiological processes in
      invertebrates. In some insects, such as honeybees and fruit flies, octopamine has
      been shown to be a major stimulator of adenylyl cyclase and to function in
      associative learning. To identify an octopamine receptor mediating this function
      in Drosophila, putative biogenic amine receptors were cloned by a novel procedure
      using PCR and single-strand conformation polymorphism. One new receptor,
      octopamine receptor in mushroom bodies (OAMB), was identified as an octopamine
      receptor because human and Drosophila cell lines expressing OAMB showed increased
      cAMP and intracellular Ca2+ levels after octopamine application.
      Immunohistochemical analysis using an antibody made to the receptor revealed
      highly enriched expression in the mushroom body neuropil and the ellipsoid body
      of central complex, brain areas known to be crucial for olfactory learning and
      motor control, respectively. The preferential expression of OAMB in mushroom
      bodies and its capacity to produce cAMP accumulation suggest an important role in
      synaptic modulation underlying behavioral plasticity.

PMID- 9570797
TI  - Activation and cleavage of caspase-3 in apoptosis induced by experimental
      cerebral ischemia.
AB  - We examined the expression, activation, and cellular localization of caspase-3
      (CPP32) using immunohistochemistry, immunoblots, and cleavage of the fluorogenic
      substrate N-benzyloxycarbonyl-Asp-Glu-Val-Asp-7-amino-4-trifluoromethyl coumarin
      (zDEVD-afc) in adult mouse brain after temporary (2 hr) middle cerebral artery
      occlusion produced by filament insertion into the carotid artery. Immunoreactive
      caspase-3p32 but not its cleavage product caspase-3p20 was constitutively
      expressed in neurons throughout brain and was most prominent in neuronal
      perikarya within piriform cortex. Caspase-like enzyme activity was elevated in
      brain homogenate 0-3 hr after reperfusion and reached a peak within 30 to 60 min.
      Caspase-3p20 immunoreactivity became prominent in neuronal perikarya within the
      middle cerebral artery territory at the time of reperfusion and on immunoblots 1
      12 hr later. DNA laddering (agarose gels) and terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick-end labeling (TUNEL)-stained cells were
      detected 6-24 hr after reperfusion. At 12-24 hr, immunoreactive p20 was
      visualized in TUNEL-positive cells, a finding also observed in apoptotic mouse
      cerebellar granule cells on postnatal day 5. Together, these observations suggest
      the existence of a time-dependent evolution of ischemic injury characterized by
      the close correspondence between caspase-like enzyme activation and an associated
      increase in immunoreactive product (caspase-3p20) beginning at or before
      reperfusion and followed several hours later by morphological and biochemical
      features of apoptosis.

PMID- 9570798
TI  - Pattern-generating role for motoneurons in a rhythmically active neuronal
      network.
AB  - The role of motoneurons in central motor pattern generation was investigated in
      the feeding system of the pond snail Lymnaea stagnalis, an important invertebrate
      model of behavioral rhythm generation. The neuronal network responsible for the
      three-phase feeding motor program (fictive feeding) has been characterized
      extensively and divided into populations of central pattern generator (CPG)
      interneurons, modulatory interneurons, and motoneurons. A previous model of the
      feeding system considered that the motoneurons were passive followers of CPG
      interneuronal activity. Here we present new, detailed physiological evidence that
      motoneurons that innervate the musculature of the feeding apparatus have
      significant electrotonic motoneuron-->interneuron connections, mainly confined to
      cells active in the same phase of the feeding cycle (protraction, rasp, or
      swallow). This suggested that the motoneurons participate in rhythm generation.
      This was assessed by manipulating firing activity in the motoneurons during
      maintained fictive feeding rhythms. Experiments showed that motoneurons
      contribute to the maintenance and phase setting of the feeding rhythm and provide
      an efficient system for phase-locking muscle activity with central neural
      activity. These data indicate that the distinction between motoneurons and
      interneurons in a complex CNS network like that involved in snail feeding is no
      longer justified and that both cell types are important in motor pattern
      generation. This is a distributed type of organization likely to be a general
      characteristic of CNS circuitries that produce rhythmic motor behavior.

PMID- 9570799
TI  - Structural features determining differential receptor regulation of neuronal Ca
      channels.
AB  - Dihydropyridine-insensitive Ca channels are subject to direct receptor G-protein
      mediated inhibition to differing extents. alpha1B channels are much more strongly
      modulated than alpha1E channels. To understand the structural basis for this
      difference, we have constructed and expressed various alpha1B and alpha1E
      chimeric Ca channels and examined their regulation by kappa-opioid receptors.
      Replacement of the first membrane-spanning domain of alpha1E with the
      corresponding region of alpha1B resulted in a chimeric Ca channel that was
      modulated by kappa-opioid receptors to a significantly greater extent than
      alpha1E. Transfer of the N terminus and I/II loop from alpha1B in addition to
      domain I resulted in a chimeric channel that was modulated to the same extent as
      alpha1B. Other regions of the molecule do not appear to contribute significantly
      to the degree of inhibition obtained, although the C terminus may contribute to
      facilitation.

PMID- 9570800
TI  - Upregulation of pleiotrophin gene expression in developing microvasculature,
      macrophages, and astrocytes after acute ischemic brain injury.
AB  - Pleiotrophin (PTN) is a heparin-binding, 18 kDa secretory protein that functions
      to induce mitogenesis, angiogenesis, differentiation, and transformation in
      vitro. PTN gene (Ptn) expression is highly regulated during development and is
      highest at sites in which mitogenesis, angiogenesis, and differentiation are
      active. In striking contrast, with the exception of the neuron, the Ptn gene is
      only minimally expressed in adults. We now demonstrate that Ptn gene expression
      is strikingly upregulated within 3 d in OX42-positive macrophages, astrocytes,
      and endothelial cells in areas of developing neovasculature after focal cerebral
      ischemia in adult rat. Ptn gene expression remains upregulated in these same
      cells and sites 7 and 14 d after ischemic injury. However, expression of the Ptn
      gene is significantly decreased in cortical neurons 6 and 24 hr after injury and
      is undetectable in degenerating neurons at day 3. Neurons in contralateral cortex
      continue to express Ptn in levels equal to control, uninjured brain. It is
      suggested that PTN may have a vital role in neovascular formation in postischemic
      brain and that postischemic brain is an important model in which to analyze
      sequential gene expression in developing neovasculature. In contrast, Ptn gene
      expression in injured neurons destined not to recover is strikingly reduced, and
      potentially its absence may contribute to the failure of the neuron to survive.

PMID- 9570802
TI  - Calcium currents and calcium signaling in rod bipolar cells of rat retinal
      slices.
AB  - Combined electrophysiological and imaging techniques were used to study calcium
      currents (ICa) and their sites of origin at rod bipolar cells in rat retinal
      slices. We report here for the first time the successful whole-cell patch-clamp
      recording from presynaptic boutons that were compared with somatic recordings.
      TTX-resistant inward currents were elicited in response to depolarization. The
      kinetic and pharmacological properties of ICa were very similar for recordings
      obtained from the soma and the presynaptic terminals. ICa activated maximally
      between -30 and -20 mV was enhanced by Bay K 8644 and was blocked by isradipine
      and nifedipine. Peak amplitude and time to peak were -31.3 +/- 1.2 pA and 3.2 +/-
      0.2 msec with somatic recordings (n = 54), whereas the corresponding values were 
      31.6 +/- 6.1 pA and 3.2 +/- 0.7 msec in recordings obtained directly from
      terminals (n = 6). ICa showed little inactivation during sustained
      depolarizations. No T-type ICa was observed with depolarizations from -90 mV.
      Concomitant with Ca2+ entry, depolarization induced the appearance of transient
      outward currents that resembled IPSCs and were blocked by GABA and glycine
      receptor antagonists, suggesting that they arise from activation of amacrine
      feedback synapses. Upon depolarization, intracellular Ca2+ ([Ca2+]i) rises were
      restricted to the presynaptic terminals with no somatic or axonal changes and
      were linearly dependent on pulse duration when using a low-affinity Ca2+
      indicator. In cone bipolar cells, ICa inactivated markedly, and [Ca2+]i rises
      occurred in the axon, as well as in the presynaptic terminals.

PMID- 9570801
TI  - Nitric oxide-dependent production of cGMP supports the survival of rat embryonic
      motor neurons cultured with brain-derived neurotrophic factor.
AB  - Trophic factor deprivation induces neuronal nitric oxide synthase (NOS) and
      apoptosis of rat embryonic motor neurons in culture. We report here that motor
      neurons constitutively express endothelial NOS that helps support the survival of
      motor neurons cultured with brain-derived neurotrophic factor (BDNF) by
      activating the nitric oxide-dependent soluble guanylate cyclase. Exposure of BDNF
      treated motor neurons to nitro-L-arginine methyl ester (L-NAME) decreased cell
      survival 40-50% 24 hr after plating. Both low steady-state concentrations of
      exogenous nitric oxide (<0.1 microM) and cGMP analogs protected BDNF-treated
      motor neurons from death induced by L-NAME. Equivalent concentrations of cAMP
      analogs did not affect cell survival. Inhibition of nitric oxide-sensitive
      guanylate cyclase with 2 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)
      reduced the survival of BDNF-treated motor neurons by 35%. cGMP analogs also
      protected from ODQ-induced motor neuron death, whereas exogenous nitric oxide did
      not. In all cases, cell death was prevented with caspase inhibitors. Our results
      suggest that nitric oxide-stimulated cGMP synthesis helps to prevent apoptosis in
      BDNF-treated motor neurons.

PMID- 9570803
TI  - Suppression of sprouting: An early function of NMDA receptors in the absence of
      AMPA/kainate receptor activity.
AB  - Electrophysiological studies have documented the existence of synapses showing
      only NMDA ionotropic glutamate receptor function that are therefore presumably
      "silent" at resting membrane potentials. Silent synapses are more prevalent in
      young than in older neurons, and NMDA receptor activity at such contacts may
      facilitate the appearance of functional AMPA receptors. However, it is uncertain
      whether such silent synapses actually have a function in young neurons
      independent of AMPA receptor induction. Using a newly characterized culture
      system for neurons from larval Xenopus tecta, we show that blocking NMDA
      receptors or preventing changes in intracellular free Ca2+ concentration with
      BAPTA AM significantly increases neurite sprouting and elongation in contacted
      but not in isolated neurons. Blocking AMPA/KA receptors or Na+-dependent action
      potentials does not mimic this effect. Moreover, in these young neurons, NMDA
      receptor-dependent Ca2+ responses to glutamate measured with confocal fluo-3
      imaging are retained during AMPA/KA receptor blockade. The data suggest that many
      of the young contacts in these cultures are active even though they use only NMDA
      ionotropic glutamate receptors. Calcium influx through the NMDA receptor at these
      contacts seems to reduce neurite motility. This effect should lead to the
      accumulation of glutamatergic inputs on NMDA receptor-expressing dendrites, which
      could facilitate the onset of AMPA/KA receptor function and the action potential
      dependent phase of synaptogenesis.

PMID- 9570804
TI  - Two phases of rod photoreceptor differentiation during rat retinal development.
AB  - We have conducted a comprehensive analysis of the relative timing of the terminal
      mitosis and the onset of rhodopsin expression in rod precursors in the rat retina
      in vivo. This analysis demonstrated that there are two distinct phases of rod
      development during retinal histogenesis. For the majority of rod precursors,
      those born on or after embryonic day 19 (E19), the onset of rhodopsin expression
      was strongly correlated temporally with cell cycle withdrawal. For these
      precursors, the lag between the terminal mitosis and rhodopsin expression was
      measured to be 5.5-6.5 d on average. By contrast, for rod precursors born before
      E19, the lag was measured to be significantly longer, averaging from 8.5 to 12.5
      d. In addition, these early-born rod precursors seemed to initiate rhodopsin
      expression in a manner that was not correlated temporally with the terminal
      mitosis. In these cells, onset of rhodopsin expression appeared approximately
      synchronous with later-born cells, suggesting a synchronous recruitment to the
      rod cell fate induced by environmental signals. To examine this possibility,
      experiments in which the early-born precursors were exposed to a late environment
      were conducted, using a reaggregate culture system. In these experiments, the
      early-born precursors appeared remarkably uninfluenced by the late environment
      with respect to both rod determination and the kinetics of rhodopsin expression.
      These results support the idea that intrinsically distinct populations of rod
      precursors constitute the two phases of rod development and that the behavior
      exhibited by the early-born precursors is intrinsically programmed.

PMID- 9570806
TI  - Removal of polysialic acid-neural cell adhesion molecule induces aberrant mossy
      fiber innervation and ectopic synaptogenesis in the hippocampus.
AB  - The mossy fiber axons of both the developing and adult dentate gyrus express the
      highly polysialylated form of neural cell adhesion molecule (NCAM) as they
      innervate the proximal apical dendrites of pyramidal cells in the CA3 region of
      the hippocampus. The present study used polysialic acid (PSA)-deficient and NCAM
      mutant mice to evaluate the role of PSA in mossy fiber development. The results
      indicate that removal of PSA by either specific enzymatic degradation or mutation
      of the NCAM-180 isoform that carries PSA in the brain causes an aberrant and
      persistent innervation of the pyramidal cell layer by mossy fibers, including
      excessive collateral sprouting and/or defasciculation of these processes, as well
      as formation of ectopic mossy fiber synaptic boutons. These results are
      considered in terms of two possible effects of PSA removal: an increase in the
      number of mossy fibers that can grow into the pyramidal cell layer and an
      inhibition of process retraction by formation of stable junctions including
      synapses. As these defects on granule cells in the adult animal and PSA-positive
      granule cells continue to be produced in the mature brain, the present findings
      may be relevant to previous studies suggesting that PSA-NCAM function is required
      for long-term potentiation, long-term depression, and learning behaviors
      associated with hippocampus.

PMID- 9570805
TI  - A neuronal form of the cell adhesion molecule L1 contains a tyrosine-based signal
      required for sorting to the axonal growth cone.
AB  - The neural cell adhesion molecule L1, which is present on axons and growth cones,
      plays a crucial role in the formation of major axonal tracts such as the
      corticospinal tract and corpus callosum. L1 is preferentially transported to
      axons and inserted in the growth cone membrane. However, how L1 is sorted to
      axons remains unclear. Tyr1176 in the L1 cytoplasmic domain is adjacent to a
      neuron-specific alternatively spliced sequence, RSLE (Arg-Ser-Leu-Glu). The
      resulting sequence of YRSLE conforms to a tyrosine-based consensus motif (YxxL)
      for sorting of integral membrane proteins into specific cellular compartments. To
      study a possible role of the YRSLE sequence in L1 sorting, chick DRG neurons were
      transfected with human L1 cDNA that codes for full-length L1 (L1FL), a non
      neuronal form of L1 that lacks the RSLE sequence (L1DeltaRSLE), mutant L1 with a
      Y1176A substitution (L1Y1176A), or L1 truncated immediately after the RSLE
      sequence (L1DeltaC77). L1FL and L1DeltaC77, both of which possess the YRSLE
      sequence, were expressed in the axonal growth cone and to a lesser degree in the
      cell body. In contrast, expression of both L1DeltaRSLE and L1Y1176A was
      restricted to the cell body and proximal axonal shaft. We also found that
      L1DeltaRSLE and L1Y1176A were integrated into the plasma membrane in the cell
      body after missorting. These data demonstrate that the neuronal form of L1
      carries the tyrosine-based sorting signal YRSLE, which is critical for sorting L1
      to the axonal growth cone.

PMID- 9570807
TI  - Age-dependent and cell class-specific modulation of retinal ganglion cell
      bursting activity by GABA.
AB  - Competition for postsynaptic targets during development is thought to be driven
      by differences in temporal patterns of neuronal activity. In the ferret visual
      system, retinal ganglion cells that are responsive either to the onset (On) or to
      the offset (Off) of light exhibit similar patterns of spontaneous bursting
      activity early in development but later develop different bursting rhythms during
      the period when their axonal arbors segregate to occupy spatially distinct
      regions in the dorsal lateral geniculate nucleus. Here, we demonstrate that
      GABAergic transmission plays an important, although not exclusive, role in
      regulating the bursting patterns of morphologically identified On and Off
      ganglion cells. During the first and second postnatal weeks, blocking GABAA
      receptors leads to a decrease in the bursting activity of all ganglion cells,
      suggesting that GABA potentiates activity at the early ages. Subsequently, during
      the period of On-Off segregation in the geniculate nucleus, GABA suppresses
      ganglion cell bursting activity. In particular, On ganglion cells show
      significantly higher bursting rates when GABAergic transmission is blocked, but
      the bursting rates of Off ganglion cells are not affected systematically. Thus,
      developmental differences in the bursting rates of On and Off ganglion cells
      emerge as GABA becomes inhibitory and as it consistently and more strongly
      inhibits On compared with Off ganglion cells. Because in many parts of the CNS
      GABAergic circuits appear early in development, our results also implicate a
      potentially important and possibly general role for local inhibitory interneurons
      in creating distinct temporal patterns of presynaptic activity that are specific
      to each developmental period.

PMID- 9570808
TI  - Carbachol stimulates [35S]guanylyl 5'-(gamma-thio)-triphosphate binding in rapid
      eye movement sleep-related brainstem nuclei of rat.
AB  - Carbachol enhances rapid eye movement (REM) sleep when microinjected into the
      pontine reticular formation of the cat and rat. Carbachol elicits this REM sleep
      like state via activation of postsynaptic muscarinic cholinergic receptors
      (mAChRs). The present study used in vitro autoradiography of carbachol-stimulated
      [35S]guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding to test the
      hypothesis that carbachol activates mAChRs to induce stimulation of G-proteins in
      brainstem nuclei contributing to REM sleep generation. The results demonstrate a
      heterogeneous increase in carbachol-stimulated G-protein activation across rat
      brainstem. Binding of [35S]GTPgammaS in the presence of carbachol, compared with
      basal binding, was significantly increased in the laterodorsal tegmental nucleus
      (75.7%), caudal pontine reticular nucleus (68.9%), oral pontine reticular nucleus
      (64.5%), pedunculopontine tegmental nucleus (55.7%), and dorsal raphe nucleus
      (54.0%) but not in the nucleus locus coeruleus. The activation of G-proteins by
      carbachol was concentration-dependent and antagonized by atropine, demonstrating
      that G-proteins were activated via mAChR stimulation. The results provide the
      first direct measures of mAChR-activated G-proteins in brainstem nuclei known to
      contribute to REM sleep generation.

PMID- 9570809
TI  - Temporal and spectral sensitivity of complex auditory neurons in the nucleus HVc
      of male zebra finches.
AB  - Complex vocalizations, such as human speech and birdsong, are characterized by
      their elaborate spectral and temporal structure. Because auditory neurons of the
      zebra finch forebrain nucleus HVc respond extremely selectively to a particular
      complex sound, the bird's own song (BOS), we analyzed the spectral and temporal
      requirements of these neurons by measuring their responses to systematically
      degraded versions of the BOS. These synthetic songs were based exclusively on the
      set of amplitude envelopes obtained from a decomposition of the original sound
      into frequency bands and preserved the acoustical structure present in the
      original song with varying degrees of spectral versus temporal resolution, which
      depended on the width of the frequency bands. Although both excessive temporal or
      spectral degradation eliminated responses, HVc neurons responded well to degraded
      synthetic songs with time-frequency resolutions of approximately 5 msec or 200
      Hz. By comparing this neuronal time-frequency tuning with the time-frequency
      scales that best represented the acoustical structure in zebra finch song, we
      concluded that HVc neurons are more sensitive to temporal than to spectral cues.
      Furthermore, neuronal responses to synthetic songs were indistinguishable from
      those to the original BOS only when the amplitude envelopes of these songs were
      represented with 98% accuracy. That level of precision was equivalent to
      preserving the relative time-varying phase across frequency bands with
      resolutions finer than 2 msec. Spectral and temporal information are well known
      to be extracted by the peripheral auditory system, but this study demonstrates
      how precisely these cues must be preserved for the full response of high-level
      auditory neurons sensitive to learned vocalizations.

PMID- 9570810
TI  - Long-distance axonal regeneration in the transected adult rat spinal cord is
      promoted by olfactory ensheathing glia transplants.
AB  - The lack of axonal regeneration in the injured adult mammalian spinal cord leads
      to permanent functional impairment. To induce axonal regeneration in the
      transected adult rat spinal cord, we have used the axonal growth-promoting
      properties of adult olfactory bulb ensheathing glia (EG). Schwann cell (SC)
      filled guidance channels were grafted to bridge both cord stumps, and suspensions
      of pure (98%) Hoechst-labeled EG were stereotaxically injected into the midline
      of both stumps, 1 mm from the edges of the channel. In EG-transplanted animals,
      numerous neurofilament-, GAP-43-, anti-calcitonin gene-related peptide (CGRP)-,
      and serotonin-immunoreactive fibers traversed the glial scars formed at both cord
      graft interfaces. Supraspinal serotonergic axons crossed the transection gap
      through connective tissue bridges formed on the exterior of the channels,
      avoiding the channel interior. Strikingly, after crossing the distal glial scar,
      these fibers elongated in white and periaqueductal gray matter, reaching the
      farthest distance analyzed (1.5 cm). Tracer-labeled axons present in SC grafts
      were found to extend across the distal interface and up to 800 microm beyond in
      the distal cord. Long-distance regeneration (at least 2.5 cm) of injured
      ascending propriospinal axons was observed in the rostral spinal cord.
      Transplanted EG migrated longitudinally and laterally from the injection sites,
      reaching the farthest distance analyzed (1.5 cm). They moved through white matter
      tracts, gray matter, and glial scars, overcoming the inhibitory nature of the CNS
      environment, and invaded SC and connective tissue bridges and the dorsal and
      ventral roots adjacent to the transection site. Transplanted EG and regenerating
      axons were found in the same locations. Because EG seem to provide injured spinal
      axons with appropriate factors for long-distance elongation, these cells offer
      new possibilities for treatment of CNS conditions that require axonal
      regeneration.

PMID- 9570811
TI  - The processing of first- and second-order motion in human visual cortex assessed
      by functional magnetic resonance imaging (fMRI).
AB  - We have examined the activity levels produced in various areas of the human
      occipital cortex in response to various motion stimuli using functional magnetic
      resonance imaging (fMRI) methods. In addition to standard luminance-defined
      (first-order) motion, three types of second-order motion were used. The areas
      examined were the motion area V5 (MT) and the following areas that were
      delineated using retinotopic mapping procedures: V1, V2, V3, VP, V3A, and a new
      area that we refer to as V3B. Area V5 is strongly activated by second-order as
      well as by first-order motion. This activation is highly motion-specific. Areas
      V1 and V2 give good responses to all motion stimuli, but the activity seems to be
      related primarily to the local spatial and temporal structure in the image rather
      than to motion processing. Area V3 and its ventral counterpart VP also respond
      well to all our stimuli and show a slightly greater degree of motion specificity
      than do V1 and V2. Unlike V1 and V2, the response in V3 and VP is significantly
      greater for second-order motion than for first-order motion. This trend is
      evident, but less marked, in V3A and V3B and absent in V5. The results are
      consistent with the hypothesis that first-order motion sensitivity arises in V1,
      that second-order motion is first represented explicitly in V3 and VP, and that
      V5 (and perhaps also V3A and V3B) is involved in further processing of motion
      information, including the integration of motion signals of the two types.

PMID- 9570812
TI  - Intersegmental coordination of limb movements during locomotion: mathematical
      models predict circuits that drive swimmeret beating.
AB  - Normal locomotion in arthropods and vertebrates is a complex behavior, and the
      neural mechanisms that coordinate their limbs during locomotion at different
      speeds are unknown. The neural modules that drive cyclic movements of swimmerets
      respond to changes in excitation by changing the period of the motor pattern. As
      period changes, however, both intersegmental phase differences and the relative
      durations of bursts of impulses in different sets of motor neurons are preserved.
      To investigate these phenomena, we constructed a cellular model of the local
      pattern-generating circuit that drives each swimmeret. We then constructed
      alternative intersegmental circuits that might coordinate these local circuits.
      The structures of both the model of the local circuit and the alternative models
      of the coordinating circuit were based on and constrained by previous
      experimental results on pattern-generating neurons and coordinating interneurons.
      To evaluate the relative merits of these alternatives, we compared their dynamics
      with the performance of the real circuit when the level of excitation was
      changed. Many of the alternative coordinating circuits failed. One coordinating
      circuit, however, did effectively match the performance of the real system as
      period changed from 1 to 3.2 Hz. With this coordinating circuit, both the
      intersegmental phase differences and the relative durations of activity within
      each of the local modules fell within the ranges characteristic of the normal
      motor pattern and did not change significantly as period changed. These results
      predict a mechanism of coordination and a pattern of intersegmental connections
      in the CNS that is amenable to experimental test.

PMID- 9570813
TI  - Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a
      food-entrained endogenous oscillator?
AB  - Several endogenous oscillators determine circadian rhythms. One, light-entrained,
      is in the suprachiasmatic nuclei (SCN), the others, food-entrained, are in
      unknown sites. To determine how the hypothalamic ventromedial nuclei (VMN) and
      feeding affect rhythms, we compared nocturnally active rats fed either ad libitum
      or for 2 hr/d during light [restricted feeding (RF)] and either with or without
      colchicine-induced disruption of VMN. We measured rhythms in temperature,
      locomotor activity, feeding, drinking, corticosterone, and the numbers of cells
      expressing c-Fos in light/dark in hypothalamic nuclei, the suprachiasmatic
      nuclei, and two major SCN targets, the subparaventricular zone (sPVNz) and
      paraventricular thalamus (pvTHAL). c-Fos cells were always light > dark in SCN,
      whereas the VMN and sPVNz lacked light/dark differences except after RF and RF
      plus VMN disruption, respectively. Controls fed ad libitum had high-amplitude
      rhythms and, generally, c-Fos cells dark > light. In RF controls, a c-Fos pattern
      dark > light occurred in VMN; generally, c-Fos cell numbers increased elsewhere
      maintaining dark > light. By contrast, levels of corticosterone peaked before
      food. In rats fed ad libitum, VMN with colchicine markedly reduced rhythm
      amplitudes, not phase. c-Fos patterns were abolished except in pvTHAL and SCN. In
      RF, VMN disruption blocked corticosterone and light/dark c-Fos patterns in all
      nuclei but produced a pattern in the sPVNz like SCN. We conclude that VMN amplify
      rhythmic output from the SCN, and the RF-induced rhythm in VMN enhances c-Fos
      activity driven by the SCN. The VMN may contain a food-entrained oscillator, and
      the sPVNz may integrate output from several oscillators.

PMID- 9570814
TI  - Memory modulation across neural systems: intra-amygdala glucose reverses deficits
      caused by intraseptal morphine on a spatial task but not on an aversive task.
AB  - Based largely on dissociations of the effects of different lesions on learning
      and memory, memories for different attributes appear to be organized in
      independent neural systems. Results obtained with direct injections of drugs into
      one brain region at a time support a similar conclusion. The present experiments
      investigated the effects of simultaneous pharmacological manipulation of two
      neural systems, the amygdala and the septohippocampal system, to examine possible
      interactions of memory modulation across systems. Morphine injected into the
      medial septum impaired memory both for avoidance training and during spontaneous
      alternation. When glucose was concomitantly administered to the amygdala, glucose
      reversed the morphine-induced deficits in memory during alternation but not for
      avoidance training. These results suggest that the amygdala is involved in
      modulation of spatial memory processes and that direct injections of memory
      modulating drugs into the amygdala do not always modulate memory for aversive
      events. These findings are contrary to predictions from the findings of lesion
      studies and of studies using direct injections of drugs into single brain areas.
      Thus, the independence of neural systems responsible for processing different
      classes of memory is less clear than implied by studies using lesions or
      injections of drugs into single brain areas.

PMID- 9570815
TI  - Long-term effects of sectioning the olivocochlear bundle in neonatal cats.
AB  - The olivocochlear bundle (OCB) was cut in neonatal cats to evaluate its role in
      the development of normal cochlear function. Approximately 1 year after
      deefferentation, acute auditory nerve fiber (ANF) recordings were made from
      lesioned animals, lesion shams, and normal controls. The degree of
      deefferentation was quantified via light microscopic evaluation of the density of
      OCB fascicles in the tunnel of Corti, and selected cases were analyzed via
      electron microscopy. In the most successful cases, the deefferentation was
      virtually complete. ANFs from successfully lesioned animals exhibited significant
      pathophysiology compared with normals and with other animals in which the surgery
      failed to interrupt the OCB. Thresholds at the characteristic frequency (CF), the
      frequency at which ANFs are most sensitive, were elevated across the CF range,
      with maximal effects for CFs in the 10 kHz region. Frequency threshold or tuning
      curves displayed reduction of tip-to-tail ratios (the difference between CF and
      low-frequency "tail" thresholds) and decreased sharpness of tuning. These
      pathological changes are generally associated with outer hair cell (OHC) damage.
      However, light microscopic histological analysis showed minimal hair cell loss
      and no significant differences between normal and deefferented groups.
      Spontaneous discharge rates (SRs) were lower than normal; however, those fibers
      with the highest SRs remained more sensitive than those with lower SRs. Findings
      suggest that the interaction between OC efferents and OHCs early in development
      may be critical for full expression of active mechanical processes.

PMID- 9570816
TI  - The variable discharge of cortical neurons: implications for connectivity,
      computation, and information coding.
AB  - Cortical neurons exhibit tremendous variability in the number and temporal
      distribution of spikes in their discharge patterns. Furthermore, this variability
      appears to be conserved over large regions of the cerebral cortex, suggesting
      that it is neither reduced nor expanded from stage to stage within a processing
      pathway. To investigate the principles underlying such statistical homogeneity,
      we have analyzed a model of synaptic integration incorporating a highly
      simplified integrate and fire mechanism with decay. We analyzed a "high-input
      regime" in which neurons receive hundreds of excitatory synaptic inputs during
      each interspike interval. To produce a graded response in this regime, the neuron
      must balance excitation with inhibition. We find that a simple integrate and fire
      mechanism with balanced excitation and inhibition produces a highly variable
      interspike interval, consistent with experimental data. Detailed information
      about the temporal pattern of synaptic inputs cannot be recovered from the
      pattern of output spikes, and we infer that cortical neurons are unlikely to
      transmit information in the temporal pattern of spike discharge. Rather, we
      suggest that quantities are represented as rate codes in ensembles of 50-100
      neurons. These column-like ensembles tolerate large fractions of common synaptic
      input and yet covary only weakly in their spike discharge. We find that an
      ensemble of 100 neurons provides a reliable estimate of rate in just one
      interspike interval (10-50 msec). Finally, we derived an expression for the
      variance of the neural spike count that leads to a stable propagation of signal
      and noise in networks of neurons-that is, conditions that do not impose an
      accumulation or diminution of noise. The solution implies that single neurons
      perform simple algebra resembling averaging, and that more sophisticated
      computations arise by virtue of the anatomical convergence of novel combinations
      of inputs to the cortical column from external sources.

PMID- 9570817
TI  - Nerve gas-induced seizures: role of acetylcholine in the rapid induction of Fos
      and glial fibrillary acidic protein in piriform cortex.
AB  - Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor
      of acetylcholinesterase (AChE), causes seizures and rapidly increases Fos and
      glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This
      suggests that the inhibition of AChE by soman leads to increased acetylcholine
      (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC
      is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in
      soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with
      192-IgG-saporin. By 10 d, saporin eliminated staining for choline
      acetyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilateral to the
      lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC
      ipsilateral to the lesioned NDB. By 45-60 min after soman, increased Fos and GFAP
      staining in PC was evident only ipsilateral to the unlesioned NDB. By 90-120 min
      after soman, Fos and GFAP staining increased bilaterally in PC. In a second
      experiment, electrical stimulation electrodes were implanted unilaterally in the
      NDB to activate focally the projections to PC in unanesthetized rats. Within 5
      min of NDB stimulation, there were clear behavioral and EEG signs of convulsions.
      After 45-60 min of NDB stimulation, there was increased Fos and GFAP staining in
      layer II of PC ipsilateral to the stimulation site. Pretreatment with the
      selective muscarinic receptor antagonist scopolamine blocked the convulsions and
      prevented increased Fos and GFAP staining in PC. These results suggest that ACh
      release in PC triggers the initiation of seizures and gliosis after soman
      administration, predominantly by the activation of muscarinic receptors.

PMID- 9570819
TI  - Dendritic spikes are enhanced by cooperative network activity in the intact
      hippocampus.
AB  - In vitro experiments suggest that dendritic fast action potentials may influence
      the efficacy of concurrently active synapses by enhancing Ca2+ influx into the
      dendrites. However, the exact circumstances leading to these effects in the
      intact brain are not known. We have addressed these issues by performing
      intracellular sharp electrode recordings from morphologically identified sites in
      the apical dendrites of CA1 pyramidal neurons in vivo while simultaneously
      monitoring extracellular population activity. The amplitude of spontaneous fast
      action potentials in dendrites decreased as a function of distance from the soma,
      suggesting that dendritic propagation of fast action potentials is strongly
      attenuated in vivo. Whereas the amplitude variability of somatic action
      potentials was very small, the amplitude of fast spikes varied substantially in
      distal dendrites. Large-amplitude fast spikes in dendrites occurred during
      population discharges of CA3-CA1 neurons concurrent with field sharp waves. The
      large-amplitude fast spikes were associated with bursts of smaller-amplitude
      action potentials and putative Ca2+ spikes. Both current pulse-evoked and
      spontaneously occurring Ca2+ spikes were always preceded by large-amplitude fast
      spikes. More spikes were observed in the dendrites during sharp waves than in the
      soma, suggesting that local dendritic spikes may be generated during this
      behaviorally relevant population pattern. Because not all dendritic spikes
      produce somatic action potentials, they may be functionally distinct from action
      potentials that signal via the axon.

PMID- 9570818
TI  - Reduced activity of hypothalamic corticotropin-releasing hormone neurons in
      transgenic mice with impaired glucocorticoid receptor function.
AB  - Loss of central glucocorticoid receptor (GR) function is thought to be involved
      in the development of neuroendocrine and psychiatric disorders associated with
      corticotropin-releasing hormone (CRH) hyperactivity. The possible causal
      relationship between defective GR function and altered activity of CRH neurons
      was studied in transgenic mice (TG) expressing antisense RNA against GR.
      Immunocytochemical studies showed significant reductions in CRH immunoreactive
      neurons in the paraventricular nucleus (PVN) and in CRH and vasopressin (AVP)
      stores in the external zone of the median eminence. Concomitantly, stimulus
      evoked CRH secretion from mediobasal hypothalami of TG mice in vitro was reduced
      significantly. However, CRH mRNA levels in the PVN of TG mice were marginally
      lower than those in wild-type (WT) mice. 125I-CRH binding autoradiography
      revealed no differences between WT and TG animals in any of the brain regions
      that were studied. Basal plasma corticosterone (cort) levels and 125I-CRH
      binding, CRH-R1 mRNA, POMC mRNA, and POMC hnRNA levels in the anterior pituitary
      gland were similar in WT and TG mice. Intraperitoneal injection of interleukin
      1beta (IL-1beta) increased plasma cort levels, CRH mRNA in the PVN, and anterior
      pituitary POMC hnRNA similarly in WT and TG mice. The injection of saline
      significantly reduced anterior pituitary CRH-R1 mRNA levels in WT mice, but not
      in TG mice, whereas IL-1beta produced a decrease in these mRNA levels in both
      strains. The data show that long-term GR dysfunction can be associated with
      reduced activity of CRH neurons in the PVN and decreased sensitivity of pituitary
      CRH-R1 mRNA to stimulus-induced downregulation. Moreover, the hypothalamic
      changes observed in this model suggest that impaired GR function, at least if
      present since early embryonic life, does not necessarily result in CRH
      hyperexpression characteristics of disorders such as major depression.

PMID- 9570820
TI  - Sensitive periods for visual calibration of the auditory space map in the barn
      owl optic tectum.
AB  - Previous studies have identified sensitive periods for the developing barn owl
      during which visual experience has a powerful influence on the calibration of
      sound localization behavior. Here we investigated neural correlates of these
      sensitive periods by assessing developmental changes in the capacity of visual
      experience to alter the map of auditory space in the optic tectum of the barn
      owl. We used two manipulations. (1) We equipped owls with prismatic spectacles
      that optically displaced the visual field by 23 degrees to the left or right, and
      (2) we restored normal vision to prism-reared owls that had been raised wearing
      prisms. In agreement with previous behavioral experiments, we found that the
      capacity of abnormal visual experience to shift the tectal auditory space map was
      restricted to an early sensitive period. However, this period extended until
      later in life (approximately 200 d) than described previously in behavioral
      studies (approximately 70 d). Furthermore, unlike the previous behavioral studies
      that found that the capacity to recover normal sound localization after
      restoration of normal vision was lost at approximately 200 d of age, we found
      that the capacity to recover a normal auditory space map was never lost. Finally,
      we were able to reconcile the behaviorally and neurophysiologically defined
      sensitive periods by taking into account differences in the richness of the
      environment in the two sets of experiments. We repeated the behavioral
      experiments and found that when owls were housed in a rich environment, the
      capacity to adjust sound localization away from normal extended to later in life,
      whereas the capacity to recover to normal was never lost. Conversely, when owls
      were housed in an impoverished environment, the capacity to recover a normal
      auditory space map was restricted to a period ending at approximately 200 d of
      age. The results demonstrate that the timing and even the existence of sensitive
      periods for plasticity of a neural circuit and associated behavior can depend on
      multiple factors, including (1) the nature of the adjustment demanded of the
      system and (2) the richness of the sensory and social environment in which the
      plasticity is studied.

PMID- 9570821
TI  - Retrograde amnesia for facts and events: findings from four new cases.
AB  - Two patients with presumed hippocampal formation lesions and two patients with
      more extensive temporal lobe damage, all of whom became amnesic in a known year,
      were given tests of anterograde and retrograde memory function. The two patients
      with hippocampal formation lesions had moderately severe anterograde amnesia and
      limited retrograde amnesia for facts and events that affected, at most, the
      decade preceding the onset of amnesia. Content analysis could not distinguish the
      autobiographical recollections of the patients from the recollections of control
      subjects. The two patients with more extensive temporal lobe damage had severe
      anterograde amnesia and extensive retrograde memory loss for both facts and
      events. The results suggest that whether retrograde amnesia is temporally limited
      or very extensive depends on whether the damage is restricted to the hippocampal
      formation or also involves additional temporal cortex.

PMID- 9570822
TI  - Response classes in the dorsal cochlear nucleus and its output tract in the
      chloralose-anesthetized cat.
AB  - Neurons in the dorsal cochlear nucleus (DCN) can be classified into three major
      physiological classes on the basis of responses to pure tone and broadband noise
      stimuli. A circuit diagram that associates these classes with different cell
      types has been proposed. According to this proposal, type II cells are inhibitory
      interneurons that respond well to tones and poorly to broadband noise, type IV
      cells are projection neurons with the opposite behavior, and type III cells are
      an inhomogeneous class with intermediate properties. To test the associations
      proposed, I compared the response type distribution in the DCN with its output
      tract, the dorsal acoustic stria (DAS), in chloralose-anesthetized cats. Axonal
      recordings in the DAS showed type III and IV responses as in DCN, but no type II
      responses. Compared with reports in decerebrate animals, fewer type IV neurons
      were encountered having sustained inhibition that generated strongly nonmonotonic
      responses to tones in both DCN and DAS. The presence of type II responses in the
      nucleus, but not in the output tract, offers strong support for the proposed
      association with DCN interneurons. On the other hand, the distinction between
      type III and IV responses needs refinement because the differences are only
      graded and because both types of responses occur in DAS, which shows that they
      are both associated with projection neurons.

PMID- 9570823
TI  - Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial
      preoptic nucleus and medial amygdala.
AB  - The mu-opioid receptor (mu-OR), like most G-protein-coupled receptors, is rapidly
      internalized after agonist binding. Although opioid peptides induce
      internalization in vivo, there are no studies that demonstrate mu-OR
      internalization in response to natural stimuli. In this study, we used laser
      scanning microscopy to demonstrate that estrogen treatment induces the
      translocation of mu-OR immunoreactivity (mu-ORi) from the membrane to an internal
      location in steroid-sensitive cell groups of the limbic system and hypothalamus.
      Estrogen-induced internalization was prevented by the opioid antagonist
      naltrexone, suggesting that translocation was largely dependent on release of
      endogenous agonists. Estrogen treatment also altered the pattern of mu-ORi at the
      bright-field light microscopic level. In the absence of stimulation, the majority
      of immunoreactivity is diffuse, with few definable mu-OR+ cell bodies or
      processes. After stimulation, the density of distinct processes filled with mu
      ORi was significantly increased. We interpreted the increase in the number of mu
      OR+ processes as indicating increased levels of internalization. Using this
      increase in the density of mu-OR+ fibers, we showed that treatment of
      ovariectomized rats with estradiol benzoate induced a rapid and reversible
      increase in the number of fibers. Significant internalization was noted within 30
      min and lasted for >24 hr after estrogen treatment in the medial preoptic
      nucleus, the principal part of the bed nucleus, and the posterodorsal medial
      amygdala. Naltrexone prevented the increase of mu-OR+ processes. These data imply
      that estrogen treatment stimulates the release of endogenous opioids that
      activate mu-OR in the limbic system and hypothalamus providing a "neurochemical
      signature" of steroid activation of these circuits.

PMID- 9570824
TI  - Compartmentalization of information processing in an aplysia feeding circuit
      interneuron through membrane properties and synaptic interactions.
AB  - We describe a pair of cerebral-to-buccal interneurons, CBI-5/6, which have
      outputs and inputs in two ganglia. The soma in the cerebral ganglion received
      synaptic inputs during buccal motor programs (BMPs) and after mechanical
      stimulation of the lips. During BMPs the soma received antidromic spikes
      generated in processes in the buccal ganglion. The soma was driven into a plateau
      potential by each of these inputs, during which it fired orthodromically at 0-5
      Hz. The soma had outputs in the cerebral ganglion consisting of electrical
      coupling to the adjacent CBI-5/6 and to a cerebral-to-pedal neuron (CPN1). The
      buccal terminals of CBI-5/6 received inputs that generated rhythmic barrages (up
      to 25 Hz) of antidromic spikes during BMPs. The buccal terminals had chemical and
      electrical outputs to motor and premotor elements of feeding circuitry. This
      combination of synaptic interactions and endogenous properties mean that CBI-5/6
      can process information in a number of ways. During the barrage of antidromic
      spikes, high-frequency firing will produce strong inputs to buccal followers and
      on their arrival at the soma will transfer excitation electrotonically to CPN1.
      Subthreshold input to the soma will be transferred electrotonically to cerebral
      followers but will not be relayed to postsynaptic buccal neurons. Plateau
      potentials after the antidromic spikes or local cerebral inputs will locally
      excite CPN1 via electrical coupling but will have little influence on buccal
      events because of the low orthodromic firing rate. Thus, CBI-5/6 may transmit
      information locally within the cerebral ganglion or more extensively in both
      buccal and cerebral ganglia simultaneously.

PMID- 9570825
TI  - Immunoassay of fumonisins by a surface plasmon resonance biosensor.
AB  - A surface plasmon resonance (SPR) immunosensor is developed to determine
      concentrations of the mycotoxin, fumonisin B1 (FB1), in spiked samples.
      Polyclonal antibodies produced against FB1 are adsorbed onto a thin gold film
      substrate, which is coupled to a glass prism in the Kretschmann configuration.
      The output beam of a planar light-emitting diode is focused through the prism to
      excite SPR at the surface of the gold film. When a sample containing FB1 is added
      to a cell on the outside of the gold film, the angular profile of reflected light
      intensity shifts. This changes the resonance angle and the reflected beam
      intensity at a selected angle, both of which are proportional to the FB1
      concentration. After optimization of the antibody overlayer, a detection limit of
      50 ng/mL is obtained for the direct assay with an analysis time under 10 min.
      Multiple sample additions and large-volume sample circulation can be used with
      the high-affinity antibodies to achieve lower detection limits.

PMID- 9570826
TI  - Determination of metallothionein by high-performance liquid chromatography with
      fluorescence detection using an isocratic solvent system.
AB  - Metallothionein (MT) is a low-molecular-weight protein which plays a role in
      detoxification of heavy metals and protection against oxidative stress. A
      sensitive and convenient determination method for MT is necessary to clarify its
      physiological roles. High-performance liquid chromatography (HPLC) with an
      isocratic solvent system for MT was, therefore, developed utilizing an unique
      fluorescence labeling reagent, ammonium 7-fluorobenz-2-oxa-1,3-diazole-4
      sulfonate (SBD-F). The HPLC system with two separation columns, Shodex RSpak RP18
      413 column (a styrene divinylbenzene polymer gel-packed column) and Puresil C18
      column (an ODS gel-packed column), connected in tandem successfully separated SBD
      labeled MT from biological interference. The SBD-labeled MT was stable and could
      be stored for at least 1 week without any changes in fluorescence intensity.
      Although Hg-MT was not detectable, this method is applicable to determination of
      major MTs such as Zn-MT, Cd-MT, and Cu-MT using commercially available rabbit MT
      as a standard. Determination of the MT concentration in cells was possible in
      aliquots of only 1 x 10(4) cultured cells. The present method using a tandem
      column HPLC system with isocratic elution might be useful for monitoring the
      concentration of MT in cultured cells as well as in animal tissues.

PMID- 9570827
TI  - Determination of non-protein-bound plasma 1,25-dihydroxyvitamin D by symmetric
      (rate) dialysis.
AB  - Most of the total circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) is bound to
      plasma proteins, mainly vitamin D-binding protein (DBP) and albumin. Only a small
      fraction in plasma exists in the free form. It is widely assumed that the non
      protein-bound free hormone reflects the biologically active fraction. We describe
      a dialysis method for the determination of plasma free 1,25(OH)2D which is
      relatively easy to perform. In this symmetric or "rate" dialysis method,
      identical samples are placed at both sides of a membrane. At one side, tritiated
      1,25(OH)2D is added and the rate of transfer of this tritiated 1,25(OH)2D through
      a dialysis membrane is directly related to the free fraction of plasma
      1,25(OH)2D. This method is much less susceptible toward tracer impurities than
      indirect equilibrium dialysis and centrifugal ultrafiltration. Moreover, it
      requires much less tracer. The intraassay coefficient of variation for the
      determination of the free fraction is 1.0%; the interassay variation is 7.7%.
      Comparison of the free fraction of 23 samples assessed with both centrifugal
      ultrafiltration and symmetric dialysis showed much higher values using the former
      method. No significant correlation between the two methods was found. The free
      fraction of 1,25(OH)2D in normal subjects as assessed with symmetric dialysis
      ranges from 0.049 to 0.103%.

PMID- 9570828
TI  - Analysis of stable oxidized molecular species of glycerophospholipids following
      treatment of red blood cell ghosts with t-butylhydroperoxide.
AB  - A model of lipid peroxidation was employed to investigate the formation of
      oxidized phospholipids in red blood cell membranes after treatment with t
      butylhydroperoxide (tBuOOH). On-line normal-phase HPLC/mass spectrometry (LC/MS)
      with electrospray ionization was used to separate phospholipid classes and
      analyze the distribution of the major poly-unsaturated fatty acyl groups and
      corresponding oxidation products. Arachidonic acid was observed primarily in
      plasmalogen glycerophosphoethanolamine (GPE), whereas linoleic acid was equally
      distributed in 1,2-diacyl-GPE and glycero-phosphocholine (GPC) lipids. The
      additions of one and two oxygen atoms to poly-unsaturated phospholipid molecular
      species were observed as the major, stable products after incubation with tBuOOH.
      Tandem mass spectrometry was utilized to further structurally characterize the
      oxidized fatty acyl groups which were identified as 5-, 8-, 9-, 11-, 12-, and 15
      hydroxy-eicosatetraenoate (HETE) and 5-, 12-, and 15-hydroperoxyeicosatetraenoate
      (HpETE) in addition to 9- and 13-hydroxyoctadecadienoate (HODE) and 9- and 13
      hydroperoxyoctadecadienoate (HpODE). Although 18:0p/20:4-GPE was the predominate
      phospholipid species containing arachidonic acid, the major species containing
      HETE and HpETE were the 1,2-diacyl-GPE with hexadecanoate as the sn-1
      substituent. This result would be consistent with a differential pathway of
      oxidative degradation of arachidonoyl plasmalogen GPE suggesting a unique role
      for this plasmalogen molecular species glycerophospholipid.

PMID- 9570829
TI  - Synthesis of 5-azido-UDP-N-acetylhexosamine photoaffinity analogs and
      radiolabeled UDP-N-acetylhexosamines.
AB  - Nuleotide sugar photoaffinity analogs have proven to be useful in the
      identification and characterization of glycosyltransferases. A radioenzymatic
      synthesis of [32P]5-azido-UDP-N-acetylglucosamine has been accomplished using 5
      azido-UTP, [gamma-32P]ATP, porcine N-acetylgalactosamine kinase, and Escherichia
      coli UDP-N-acetylglucosamine pyrophosphorylase, GlmU. This general enzymatic
      scheme was useful for the synthesis of [32P]5-azido-UDP-N-acetylgalactosamine and
      high-specific-activity [3H] or [32P]UDP-N-acetylhexosamines. A new chemical
      synthesis method for generating 5-azido-uridine compounds was also developed.
      [32P]5-Azido-UDP-N-acetylglucosamine was functionally characterized using
      different soluble and membrane-associated glycosyltransferases which utilize UDP
      GlcNAc as a substrate. Site-specific photoincorporation was observed for
      partially purified GlmU and porcine UDP-GlcNAc pyrophosphorylase. The photoprobe
      also effectively photoincorporated into the alpha- and beta-subunits of purified
      bovine UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1
      phosphotransferase. Lastly, the photoprobe was also effective at photolabeling
      Streptococcus pyogenes hyaluronate synthase in membrane preparations.

PMID- 9570830
TI  - Microbial transglutaminase-mediated synthesis of hapten-protein conjugates for
      immunoassays.
AB  - Hapten-protein conjugates are essential in many immunochemical assays, in
      particular, in assays employing titration or competitive assay formats. By
      exploitation of the catalytic properties of the microbial transglutaminase from
      Streptoverticillium mobarense sp. (MTGase), i.e., acyl transfer between gamma
      carboxamide groups and various primary amines, new techniques for the synthesis
      of hapten-protein conjugates were developed. This is demonstrated by two
      examples. The feasibility of MTGase for hapten-protein conjugate synthesis was
      studied by coupling the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) to
      casein. Different procedures for the synthesis and the immobilization of these
      2,4-D-casein conjugates were evaluated, comprising (i) a batch procedure, (ii)
      coupling of 2,4-D to an already immobilized layer of casein, and (iii) a method
      for simultaneous immobilization and conjugation. Kinetic studies revealed that
      conjugate formation in the batch procedure was almost complete after approx 2 h.
      By employing the conjugates in a competitive ELISA, detection limits as low as
      0.05 microgram/L 2,4-D were reached. Using the approach with simultaneous
      immobilization and conjugation, the time for the whole assay could be reduced to
      only 2 h. Finally, to demonstrate the versatility of the enzymatic synthesis of
      hapten-protein conjugates, an ELISA for 2,4,6-trinitrotoluene (TNT) determination
      based on transglutaminase-synthesized conjugates was developed. In this assay, a
      detection limit as low as 0.04 microgram/l TNT was obtained.

PMID- 9570831
TI  - Quantitation of estrogen receptor mRNA copy numbers in breast cancer cell lines
      and tumors.
AB  - Several clinical studies have suggested that the content of estrogen receptor
      (ER) in breast tumors influences the survival, tumor recurrence, and response to
      antiestrogen therapies. Therefore, the ability to precisely quantitate the ER
      content in tumor tissues will be of significant benefit to women with breast
      cancer. Although immunohistochemical and polymerase chain reaction (PCR) methods
      have been described for the detection and semiquantitation of ER, none of them
      precisely quantitate ER copy numbers in tumor samples. In the present report we
      describe a molecular approach to accurately quantitate ER mRNA copy numbers using
      a reverse-transcription PCR (RT-PCR) template competition method. A competitor
      template was devised by inserting unrelated nucleic acid sequences into an ER
      cDNA clone. A template competitive RT-PCR analysis was then performed to
      determine the number of copies of ER mRNA. As a standard of reference for the ER
      mRNA copy numbers from various samples, the mRNA copy numbers of a constitutively
      expressed gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were also
      quantitated. The ER quantitations were performed in three positive cell lines,
      MCF-7, T47D, and ZR-75, and two positive tumor tissues by this approach. Our
      results described here show that among the cell lines studied, T47D expresses the
      highest copy numbers of ER. We also present here that ER as low as 10(3) copies
      per 10(5) copies of GAPDH can be detected and quantitated in tumor samples by the
      template competition method. In addition, the molecular approach can
      simultaneously detect, distinguish, and quantitate exon deletion variant copy
      numbers of ER. The results described in this report indicate that the ratios of
      exon 7 deletion variant to wild type in the tumor tissues are significantly
      higher than in the cell lines studied.

PMID- 9570832
TI  - Stable transfection of mammalian cells by syringe-mediated mechanical loading of
      DNA.
AB  - We show that mammalian cells can be stably transfected by a mechanical loading
      procedure in which cells are forced through a small opening in the presence of
      DNA. A suspension of cells and plasmid DNA in growth medium was passed up and
      down through a 30-gauge needle attached to a 1-ml syringe. Cells were immediately
      plated at appropriate densities for subsequent selection for stable expression of
      a marker gene. Two rodent cell lines, Chinese hamster ovary and mouse Ltk- cells,
      were successfully transfected with an efficiency of about one transfectant per 5
      x 10(4) cells. The human HeLa cell line was transfected with a somewhat lower
      efficiency. Pluronic F-68, a detergent believed to aid in healing of membrane
      injuries, had no beneficial effect when present during the loading procedure.
      Successful transfection was accomplished using three different genes as
      selectable markers. Southern blotting analysis revealed that transfectants
      contained one or very few copies of the introduced DNA construct integrated into
      the genome. Several transfectants were demonstrated to remain stable for more
      than 20 generations of growth in the absence of selection. This procedure is
      fast, economical, and of general utility.

PMID- 9570833
TI  - The modified DNA base beta-D-glucosylhydroxymethyluracil confers resistance to
      micrococcal nuclease and is incompletely recovered by 32P-postlabeling.
AB  - The hypermodified DNA base beta-D-glucosylhydroxymethyluracil, also called J, is
      a naturally occurring DNA modification. J was initially detected by 32P
      postlabeling in Trypanosoma brucei and was recently also found in several other
      eukaryotic parasites. To use 32P-postlabeling as a method to quantitate the
      absolute levels of J in DNA we have tested the postlabeling efficiency of J using
      various synthesized standard oligonucleotides containing J. It is known that
      modified nucleotides, especially bulky ones, are often partially recovered by
      postlabeling and they are poor substrates for some of the enzymes used. We found
      that on average only 50% of J is recovered, which shows that the amount of J in
      T. brucei DNA has been twofold underestimated. Experiments with a short oligomer
      and defined pyrimidine tracts showed that the incomplete recovery of J is caused
      at least in part by resistance of J-containing DNA to degradation by micrococcal
      nuclease.

PMID- 9570834
TI  - Evaluation of five imidazopyrazinone-type chemiluminescent superoxide probes and
      their application to the measurement of superoxide anion generated by Listeria
      monocytogenes.
AB  - Superoxide-triggered chemiluminescence of five new imidazopyrazinone derivatives
      was investigated using the hypoxanthine-xanthine oxidase system as the source of
      superoxide anion. The results showed that they are highly sensitive and have
      favorable properties in measuring superoxide anion. With those new probes, the
      generation of superoxide anion from the bacteria Listeria monocytogenes was
      examined. The results confirmed the previous report that L. monocytogenes is an
      unusual organism that extracellularly and continuously generates a high level of
      superoxide anion in the presence of acetaldehyde. The data indicated that two of
      the probes, 3,7-dihydro-2-methyl-6-phenylethynylimidazo[1,2-a]pyrazin-3- one (4)
      and its methoxy derivative (5), are highly sensitive and useful in the
      measurements of superoxide anion and are clearly superior to 3,7-dihydro-2-methyl
      6-(4-methoxyphenyl)imidazo[1,2-a]pyrazin-3-on e (MCLA), which-has been generally
      considered the most sensitive superoxide probe in the past. When tested at a
      probe concentration of 3.3 microM, the luminescence response and the signal
      background ratio of compound 4 were 1.5 and 2.5 times those of MCLA,
      respectively, and the signal-background ratio of compound 5 was almost 15 times
      that of MCLA, though the luminescence response of this compound was slightly
      lower than that of MCLA. The low probe concentration used enhances the usefulness
      of probes in the measurements of superoxide in functioning biological systems.

PMID- 9570835
TI  - Reversed-flow affinity elution applied to the purification of carboxypeptidase Y.
AB  - In the present study we describe a novel method for obtaining highly pure
      carboxypeptidase Y, or derivatives thereof, in a single-step purification
      procedure. The method is based on affinity chromatography and the results
      demonstrate that an efficient method is obtained only when the affinity gel is
      fully saturated with enzyme. Thus, pilot experiments are required to determine
      the binding capacity of the resin with respect to a given enzyme. To avoid this
      additional experimental effort, we have developed a method utilizing reversed
      flow affinity elution. The method has been successfully employed to purify
      hundreds of carboxypeptidase Y mutant enzymes.

PMID- 9570836
TI  - A quantitative cryogenic gel-shift technique for analysis of protein-DNA binding.
AB  - A cryogenic gel mobility shift technique was developed in which a mixture of
      protein and DNA samples at equilibrium is rapidly quenched and electrophoresed at
      -40 degrees C. The rapid and sustained drop in temperature results in almost
      complete stabilization of the equilibrium species distribution. Autoradiogram
      analysis of relative abundances for the bound and free DNA sites is carried out
      over a range of initial binding ratios to yield the binding curve and equilibrium
      constant as in the usual gel-shift assay. Validity of this technique for
      determining equilibrium populations of the interacting species is based upon two
      testable assumptions: (i) The equilibrium species distribution does not change
      during the cryogenic quench procedure. (ii) This equilibrium distribution is also
      constant during electrophoresis of the sample. Evidence supporting these
      assumptions was obtained using lambda cI repressor and a 570-bp DNA fragment
      containing the repressor binding site OR1. The resolved free energy for this
      interaction (delta G1) was shown to be independent of the quench procedure,
      duration of the quench stage, residence time in the gel wells, and duration of
      low-temperature electrophoresis. The technique yielded a free energy that was in
      close agreement with those from filter binding and DNAse footprint titration
      methods. This cryogenic version of the gel-shift method may prove especially
      useful in cases like that of lambda cI/OR1 binding, for which conventional gel
      shift methodology has not been feasible.

PMID- 9570837
TI  - Synthesis of a radiolabeled zwitterionic detergent and its use in protein
      purification.
AB  - Radiolabeling permits the detection of trace amounts of zwitterionic detergent
      remaining in extracted hydrophobic or membrane proteins. To develop a sensitive
      and specific assay for its presence, the commonly used zwitterionic membrane
      protein detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate
      (Chaps) was synthesized in a tritiated form. Synthesis via 7-ketodeoxycholic acid
      gave [7-3H]Chaps in 53% yield with a specific activity of 0.85 mCi/mmol. A novel
      solvent extraction system for cholic acid obviated the need for chromatographic
      isolation of this intermediate. The protocol can be readily modified to yield [7
      3H]Chaps of higher specific activity. [7-3H]Chaps was used to monitor the
      efficiency of various strategies for detergent removal from concentrated
      bacterial culture supernatants containing 0.2% (w/v) Chaps. Dialysis removed 95%
      of Chaps and the addition of detergent-affinity beads to the dialysis buffer
      resulted in 97% removal of Chaps. Gel-filtration chromatography removed 99.9% of
      Chaps, while a detergent-affinity bead chromatography column removed 99.99%.
      Overall, gel-filtration chromatography was the most convenient and economical
      method for the one-step removal of the zwittergent from complex biological
      mixtures.

PMID- 9570838
TI  - Dissection of hepatic receptor-mediated endocytic pathways using self-generated
      gradients of iodixanol (Optiprep).
AB  - Iodixanol is a new, nonionic, iodinated density gradient medium which has an
      advantage over other similar media in that it rapidly forms self-generated
      gradients in vertical or near-vertical rotors. Endocytosis of 99mTc-labeled
      neogalactosyl albumin (99mTc-NGA), a synthetic ligand for the asialoglycoprotein
      receptor, was studied by administering the ligand as a short pulse to perfused
      rat livers operating under single-pass conditions. Intracellular processing was
      arrested at various times after the pulse and the resultant homogenate cleared of
      nuclei and heavy mitochondria by centrifugation at 3000 g for 10 min. After
      adjustment to 12.5% (w/v) iodixanol, the 3000 g supernatants were centrifuged at
      350,000 g for 60 min to form the gradients in which early, clathrin-containing
      vesicles, low-density endosomes, and lysosomes were well-resolved. 99mTc-NGA
      bound to the sinusoidal membrane could be partially resolved from clathrin
      containing vesicles by inclusion of 1 mM CaCl2 in the homogenization and gradient
      buffers. Two populations of early clathrin-containing vesicles could be resolved
      by rate-zonal centrifugation in preformed iodixanol gradients. Thus, iodixanol is
      an excellent density gradient medium for the rapid and efficient resolution of
      endosome compartments.

PMID- 9570839
TI  - Improving the recovery of lysine in automated protein sequencing.
AB  - Automated protein sequencing is an important tool in protein characterization.
      Most instruments use tetrahydrofuran (THF) as the HPLC eluent for separation of
      the derivatized amino acids residues. THF is highly perishable when exposed to
      air, generating peroxides which can degrade amino acids, mainly lysine, leading
      to uncertainty in chromatogram interpretations. Modifications of the existing
      HPLC equipment were introduced to create a permanent inert atmosphere inside the
      bottle of THF solution. This was carried out by changing the argon plumbing and
      some electrical connections and by reprogramming the software of the protein
      sequencer. The positive results of this procedure were demonstrated by comparing
      the decreasing lysine peak area during 28 days before and after the
      modifications. In the modified instrument, lysine recovery was much better as a
      function of the age of the THF eluent. Since these modifications improved the
      instrument performance, they have been adopted for routine use in our laboratory.

PMID- 9570840
TI  - Optimization of the cleavage reaction for cyanylated cysteinyl proteins for
      efficient and simplified mass mapping.
AB  - Peptide chains can be cleaved selectively on the N-terminal side of cysteine
      residues after cyanylation of sulfhydryl groups to form an amino-terminal peptide
      and a series of 2-iminothiazolidine-4-carboxyl peptides. This paper describes a
      systematic study that was carried out to elucidate the effects of peptide
      structure and reaction conditions on the kinetics of the reactions and the yields
      of cleavage products. Both cleavage and beta-elimination reactions under
      different conditions (pH 8.0, 9.0, and 12.0 and 1 M ammonia solution) were
      quantitatively evaluated using reversed-phase HPLC and matrix-assisted laser
      desorption/ionization-MS. Contrary to previous reports, our results showed that
      higher pH greatly accelerates both cleavage and beta-elimination reactions, while
      the relative yield of beta-elimination products does not increase for most of the
      peptides studied. Optimal results were obtained in 1 M ammonium hydroxide
      solution, in which cleavage is complete within an hour at ambient temperature.
      This improvement also minimizes side reactions otherwise associated with long
      hours of exposure to alkaline conditions, [original report called for 12 to 80 h
      of incubation in mildly alkaline (pH 8-9) buffer]. The yields of cleavage
      reactions depend primarily on the structure of amino acids on the N-terminal side
      of cyanylated cysteines; the Pro-Cys and Tyr-Cys bonds were resistant to
      cleavage, promoting beta-elimination as the main reaction. The improved cleavage
      conditions greatly simplify the analytical procedure, which has been successfully
      applied to the determination of cysteine status in spinach ferredoxin, ovalbumin,
      and rabbit muscle creatine phosphokinase.

PMID- 9570841
TI  - Methyl-beta-cyclodextrins and liposomes as water-soluble carriers for cholesterol
      incorporation into membranes and its evaluation by a microenzymatic fluorescence
      assay and membrane fluidity-sensitive dyes.
AB  - A variety of methods to incorporate cholesterol into lipid membrane systems have
      been applied with varying success. We tested an incorporation method based on
      cholesterol-loaded methyl-beta-cyclodextrins and compared it to a method that
      uses cholesterol-loaded liposomes. With methyl-beta-cyclodextrin, we increased
      the cholesterol content in microsomal membranes to almost the fourfold of the
      original content. With cholesterol-loaded liposomes instead, we achieved an
      elevation of 140%. Short incubation times and well-defined carrier properties
      favor the beta-cyclodextrin method. For direct detection of membrane cholesterol,
      we slightly modified a microenzymatic fluorescence assay originally developed for
      precise cholesterol detection in serum. Without the need to perform lipid
      extraction, this assay was reliable for cholesterol detection in liposomes and in
      microsomes. Additionally, we compared the sensitivity of the fluidity-sensitive
      fluorescent dyes pyrene, pyrene-methanol, bis-pyrene, 1-6-phenyl-1,3,5,
      hexatrien, and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5,-hexatrien in order
      to detect cholesterol indirectly by the dynamically relevant changes exerted on
      lipid matrices. These dyes differ not only in their membrane location but also in
      their dynamical behavior. We calibrated the dyes in liposomes of defined
      cholesterol content and used the most suited ones to follow and quantify the
      cholesterol incorporation into liposomal and microsomal membranes.

PMID- 9570842
TI  - Identification of posttranslational modifications and cDNA sequencing errors in
      the rat S100 proteins MRP8 and 14 using electrospray ionization mass
      spectrometry.
AB  - MRP8 and 14 are S100 proteins expressed by myeloid cells and are predicted to
      have important functions in inflammation. The proteins were isolated from spleens
      from three rat strains. Electrospray ionization mass spectrometry indicated
      masses of 10,149 +/- 2 Da for MRP8 and 13,069 +/- 2 Da for MRP14 compared to
      masses calculated from proteins derived from their cDNA sequences of 10,211 and
      13,214 Da, respectively, indicating posttranslational modifications and/or errors
      in the derived protein sequences. Several endoprotease digest peptides did not
      correspond to any theoretical digest products after comparison of ESI masses with
      those derived from the theoretical digest. Both proteins were N-terminally
      acetylated after deletion of the initiator Met, reducing the theoretical masses
      by 89 Da. A peptide with mass 28 Da greater than the theoretical was isolated
      from the Asp N digestion of MRP8. N-terminal sequencing indicated translated Val
      instead of the predicted Ala at position 72 of MRP8. A peptide 56 Da less than
      the theoretical was isolated from the chymotryptic digestion of MRP14, and the
      carboxyamidomethylated form was N-terminally sequenced and found to have
      translated Ser instead of the predicted Arg at position 105. In addition, His106
      was methylated. The corrected theoretical masses, incorporating the
      posttranslational modifications and sequencing errors, are 10,149.4 and 13,069.9
      Da for MRP8 and 14, respectively, in good agreement with the experimental masses.

PMID- 9570843
TI  - Use of a light-addressable potentiometric sensor for the detection of Escherichia
      coli O157:H7.
AB  - We describe the development of an immunoligand assay (ILA) in conjunction with a
      light-addressable potentiometric sensor (LAPS) for the rapid detection of
      Escherichia coli O157:H7 cells in buffered saline. The ILA protocol consists of
      "sandwiching" bacterial analyte between biotinylated and fluoresceinated
      antibodies, indirect enzyme labeling of the bacteria with urease-labeled anti
      fluorescein antibody, and active capture of the immune complex at a biotinylated
      bovine serum albumin-blocked nitrocellulose filter membrane with streptavidin.
      Using live E. coli O157:H7, the efficiency of the ILA was compared using various
      ratios of the biotinylated and fluoresceinated antibodies. Simultaneous addition
      of equimolar biotinylated and fluoresceinated antibodies effected optimal urease
      labeling and subsequent active capture of the bacteria in the ILA. Equimolar
      concentrations of the antibodies were varied to achieve optimal LAPS detection
      response for the live bacteria. Using ILA with LAPS, a minimum detectable level
      of ca. 7.1 x 10(2) cells/ml of heat-killed or ca. 2.5 x 10(4) cells/ml of live E.
      coli O157:H7 bacteria was achieved in Tris-buffered saline in an assay time of
      ca. 45 or ca. 30 min, respectively.

PMID- 9570844
TI  - Assay of protein-bound lipoic acid in tissues by a new enzymatic method.
AB  - A new enzymatic method for the determination of protein-bound lipoic acid was
      established. Bound lipoyl groups were liberated in the form of lipoyllysine by
      protease digestion and assayed by lipoamide dehydrogenase (NADH:lipoamide
      oxidoreductase, EC 1.8.1.4)-mediated NADH oxidation. NADH oxidation was coupled
      to reduction of the lipoyl disulfide group. Fluorescence kinetics of NADH
      oxidation were markedly enhanced by the addition of glutathione disulfide,
      recycling the enzyme-mediated lipoyl/dihydrolipoyl conversion. In the presence of
      a large excess of glutathione disulfide, NADH oxidation follows pseudo-first
      order kinetics in terms of lipoyllysine concentration. A good linear correlation
      is obtained between the oxidation rate and lipoyllysine concentration up to 5
      microM and the calibration curve indicates that the detection limit could be 100
      nM lipoyllysine. The method was applied to protease lysates of bovine, rat, and
      rabbit tissues to determine lipoyllysine levels. Kidney and liver were found to
      have the highest content of lipoyllysine in the range of 3.9 to 4.6 nmol/g rat or
      rabbit wet tissue or 11.6 to 13.1 nmol/g bovine acetone powder.

PMID- 9570845
TI  - Detection of lectins using ligand blotting and polyacrylamide-type glycoconjugate
      probes.
AB  - A sensitive and convenient method for detection of the carbohydrate-binding
      activity of lectins was established using the combination of blotting of lectins
      on polyvinylidene difluoride membranes, carbohydrate-conjugated biotinylated
      polyacrylamide-type probes (carbohydrate-bp probes), horseradish peroxidase
      streptavidin, and detection by enhanced chemiluminescence of the enzyme reaction.
      This method was tested for detection of four plant lectins blotted on the
      membrane: concanavalin A was detectable down to 100 ng by mannose-bp probe,
      Ricinus communis agglutinin 120 to as low as 5 ng by N-acetyllactosamine-bp
      probe, soybean agglutinin to 1 microgram by beta-N-acetyl-D-galactosamine-bp
      probe, and wheat germ agglutinin to 5 ng by beta-N-acetyl-D-glucosamine-bp probe.
      All four lectins were detectable on an electroblotted membrane after SDS
      polyacrylamide gel electrophoresis. This method was used to detect recombinant
      human galectin-3 in Escherichia coli cell lysates and mannan-binding protein in
      human serum. These results indicate that this method is widely applicable to
      convenient detection and characterization of lectins in crude samples.

PMID- 9570846
TI  - Quantification of Eu3+ in quantum-dye-labeled materials by ashing and
      dissociation enhancement.
AB  - Quantum Dye (QD) is an extremely stable macrocyclic chelate of Eu3+, measurable
      with a time-resolved fluorometer even without the aid of enhancement solution,
      albeit at a low sensitivity. However, QD is not easily quantified by the popular
      dissociation-enhancement methodology (I. Hemmila et al., 1984, Anal. Biochem.
      137, 335-343), because of difficulty in dissociating Eu3+ completely from QD. We
      found that Eu3+ in QD can be accurately measured by simple ashing followed by the
      dissociation-enhancement methodology. Validity of the method was tested by
      determining Eu(NO3)3 with or without ashing and analyzing Eu3+ in other chelates
      known to be amenable to accurate measurement by the dissociation enhancement.

PMID- 9570847
TI  - Assay of low deuterium enrichment of water by isotopic exchange with [U
      13C3]acetone and gas chromatography-mass spectrometry.
AB  - A sensitive assay of the 2H-enrichment of water based on the isotopic exchange
      between the hydrogens of water and of acetone in alkaline medium is described and
      validated. For low 2H-enrichments (0.008 to 0.5%), the sample is spiked with [U
      13C3]acetone and NaOH. After exchange, 2H-enriched [U-13C3]acetone is extracted
      with chloroform and assayed by gas chromatography-mass spectrometry. With some
      instruments, ion-molecule reactions, resulting in increased baseline enrichment,
      are minimized by lowering the electron ionization energy from the usual 70 to 10
      eV. The 2H-enrichment of water is amplified nearly sixfold in the M4/M3 ratio of
      [U-13C3]acetone. For high 2H-enrichments (0.25 to 100%), the use of unlabeled
      acetone suffices. After exchange, the mass isotopomer distribution of acetone is
      analyzed, yielding the 2H-enrichment of water. The assay with [U-13C3]acetone
      allows measuring the 2H-enrichment of water even in biological samples containing
      acetone. This technique is more rapid and economical than the classical isotope
      ratio mass spectrometric assay of the enrichment of hydrogen gas derived from the
      reduction of water.

PMID- 9570848
TI  - Development of chemiluminescence-based methods for specific quantitation of
      nitrosylated thiols.
AB  - While nitrosothiol compounds have been hypothesized to be important in the
      transport and function of nitric oxide (NO) in biological systems many important
      questions regarding their mechanism of formation and functional importance
      remain. In view of these fundamental questions there has been a great need for
      simple, sensitive, and specific methods for quantitation of nitrosothiols in
      biological samples. We report the development of two methods, for the measurement
      of nitrosothiol compounds using a chemiluminescence nitric oxide analyzer with a
      standard purging vessel. The first method is based on treatment with acidified
      solutions of potassium iodide in the presence or absence of dissolved free
      iodine. Quantitative release of NO occurs either from both nitrite and
      nitrosothiols or from nitrite alone, respectively. Subtraction of the amount of
      NO released without iodine from NO released in the presence of iodine allows
      estimation of the nitrosothiol concentration. To selectively measure
      nitrosothiols, we developed a redox quinone-hydroquinone alkaline reactant that
      selectively releases NO from nitrosothiols. This reactant quantitatively converts
      nitrosothiols to NO at elevated temperature, > 60 degrees C. Both methods were
      shown to detect nitrosothiols in biological buffers or blood plasma down to 10 nM
      concentration with high accuracy and reproducibility, variability less than 5%.
      These assays should be a useful addition to techniques used to characterize the
      biochemistry of NO.

PMID- 9570849
TI  - Analysis of the DNA damage induced by phenyl glycidyl ether using capillary zone
      electrophoresis-electrospray mass spectrometry.
AB  - The in vitro adduct formation between phenyl glycidyl ether (PGE) and calf thymus
      DNA was investigated. Agarose slab gel electrophoresis of DNA incubated with PGE
      revealed that nearly all high-molecular-weight species were degraded after 10 h
      of incubation. After DNA precipitation the reaction products present in the
      supernatant were subjected to a solid-phase extraction on a polystyrene
      divinylbenzene copolymer, enabling analysis on capillary zone electrophoresis
      (CZE), using sample stacking. These reaction products were mainly produced during
      the first 10 h of incubation, indicating that these products result from the DNA
      degradation. On the other hand, analysis of the adducts present in the enzymatic
      digest of the DNA pellet revealed that these adducts were formed only after 10 h
      of incubation. The reaction products present in the DNA supernatant were
      identified by on-line coupling of CZE to electrospray tandem mass spectrometry.
      Three major reaction products resulted from phosphate alkylation, as proven by
      the analysis of the corresponding low-energy CAD product ion mass spectra. This
      phosphate alkylation results in phosphotriesters which readily hydrolyze,
      resulting in DNA strand breaks.

PMID- 9570850
TI  - Formation of carbonyls during attack on insulin by submolar amounts of
      hypochlorite.
AB  - Bovine insulin was reacted at pH 4.0 with submolar amounts of hypochlorite. At
      least one molecule of insulin was modified per two molecules of hypochlorite
      added, as estimated by HPLC of native and modified insulin. About 5% of the
      hypochlorite-modified insulin reacted with dinitrophenylhydrazine (DNPH), a
      reagent which specifically labels carbonyl groups. The major DNPH-labeled product
      was isolated from the native insulin on reverse-phase HPLC, using trifluoroacetic
      acid/water/acetonitrile gradients. The UV spectrum of the major peak on the HPLC
      diode-array detector was representative of DNPH adducts, with lambda max = 365
      nm. Several methods, including total amino acid analysis, tryptic digestion, and
      collision-induced dissociation-electrospray MS, indicate that the major carbonyl
      in the DNPH-labeled product was on the amino-terminal phenylalanine of the
      insulin B-chain. Amino acid analysis indicated that tyrosine was also degraded by
      hypochlorite, but we could not detect a carbonyl group formed at tyrosine. These
      findings suggest that the terminal amino groups of proteins are highly vulnerable
      to carbonyl formation during hypochlorite attack. The use of relatively low
      amounts of active oxygen species (such as hypochlorite), followed by
      chromatographic isolation of the protein labeled with a carbonyl-specific
      reagent, can be a useful approach to the study of reactive sites on proteins.

PMID- 9570851
TI  - Comprehensive two-dimensional high-performance liquid chromatography for the
      isolation of overexpressed proteins and proteome mapping.
AB  - A two-dimensional liquid chromatographic system is described here which uses size
      exclusion liquid chromatography (SEC) followed by reversed-phase liquid
      chromatography (RPLC) to separate the mixture of proteins resulting from the
      lysis of Escherichia coli cells and to isolate the proteins that they produce.
      The size-exclusion chromatography can be conducted under either denaturing or
      nondenaturing conditions. Peaks eluting from the first dimension are
      automatically subjected to reversed-phase chromatography to separate similarly
      sized proteins on the basis of their various hydrophobicities. The RPLC also
      serves to desalt the analytes so that they can be detected in the deep
      ultraviolet region at 215 nm regardless of the SEC mobile phase used. The two
      dimensional (2D) chromatograms produced in this manner then strongly resemble the
      format of stained 2D gels, in that spots are displayed on a X-Y axis and
      intensity represents quantity of analyte. Following chromatographic separation,
      the analytes are deposited into six 96-well (576 total) polypropylene microtiter
      plates via a fraction collector. Interesting fractions are analyzed by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI
      TOF/MS) or electrospray mass spectrometry (ESI/MS) depending on sample
      concentration, which both yield accurate (2 to 0.02%) molecular weight
      information on intact proteins without any additional sample preparation,
      electroblotting, destaining, etc. The remaining 97% of a fraction can then be
      used for other analyses, such Edman sequencing, amino acid analysis, or
      proteolytic digestion and sequencing by tandem mass spectrometry. This 2D HPLC
      protein purification and identification system was used to isolate the src
      homology (SH2) domain of the nonreceptor tyrosine kinase pp60c-src and beta
      lactamase, both inserted into E. coli, as well as a number of native proteins
      comprising a small portion of the E. coli proteome.

PMID- 9570852
TI  - A time-resolved immunofluorometric assay of sialyl Lewis x-degrading alpha 2,3
      sialidase activity.
AB  - We have developed an assay for alpha 2,3-sialidase (EC 3.2.1.18) which employs a
      biotinylated carbohydrate-polyacrylamide conjugate as substrate for the enzyme.
      The solution-phase sialidase reactions are followed by a selective capture of
      biotinylated neoglycoconjugates onto a microtitration plate coated with
      streptavidin. The amount of the reaction product formed is then rapidly and
      easily quantified using a product-specific primary antibody and europium chelate
      labeled secondary antibody. This method combines the advantages of solution-phase
      enzymatic reaction and suitability for high-throughput screening typical of solid
      phase assays. The assay gives a detectable signal with 0.4% of substrate sites
      desialylated. We have demonstrated the utility of the assay by measuring alpha
      2,3-sialidase activity from crude lysates of cultured rat endothelial cells by
      using biotinylated sialyl Lewis x glycoconjugate as substrate. Endothelial
      sialidase(s) showed up to 250-fold higher activity toward soluble compared to
      immobilized substrate. Product formation detected with an anti-Lewis x antibody
      was linear in the range of 0.1-4 micrograms/ml of protein in endothelial cell
      lysate. High sensitivity of the assay was achieved by using solution-phase enzyme
      reaction and time-resolved fluorometric detection. The same assay format used
      here is easily adapted to detect activities of several different glycosidases or
      glycosyl-transferases by using appropriate substrates and antibodies.

PMID- 9570853
TI  - Standardization of a spectrophotometric assay for plasma total antioxidant
      capacity.

PMID- 9570854
TI  - A chromatographic method for the preparative separation of phosphohistidines.
AB  - The driving force behind this new chromatographic technique was to develop a
      method for purifying preparative quantities of phosphohistidines in a single step
      that provided good resolution wit eluants that could be easily removed. The
      current method can provide milligram quantities of each phosphohistidine;
      however, the later 1H NMR analysis of the dried, individually purified
      phosphohistidines showed that histidine was present along with each of the
      individual phosphohistidines. The stability of each phosphohistidine during
      storage does not appear to be a problem because the amounts of histidine
      contamination of freshly freeze-dried samples were compared with those of samples
      stored at -80 degrees C under nitrogen for 2 weeks and were found to be similar
      (data not shown). Possibly, the lyophilization and preparation of solutions for
      NMR analysis resulted in a certain amount of hydrolysis of phosphohistidine,
      particularly with the less stable 1- and 1,3-forms (5, 6). It was noted that when
      the lyophilized samples were initially dissolved in D2O for NMR analysis, the pH
      was between 6 and 7; this may have resulted in some hydrolysis of the
      phosphohistidines. This hydrolysis can be reduced by the addition of 50 mM
      potassium hydroxide to the pooled fractions collected from the chromatography, so
      that the alkalinity of the samples is maintained throughout the subsequent
      processes. The data obtained for the assignment of individual phosphohistidines
      by 1H and 31P NMR analysis seem consistent with those obtained by other
      independent studies (6, 10). The NMR analysis was a powerful tool in assigning
      the identity of each purified phosphohistidine, although caution should be used
      when considering free phosphohistidines as references for NMR detection of
      phosphohistidines in native proteins. Lecroisey et al. (10) showed that there
      were differences between the chemical shifts observed for free phosphohistidine
      compared to those for phosphohistidine in dipeptides. However, for the purposes
      of phosphoamino acid analysis, these purified phosphohistidines are used by this
      group as references in the detection of phosphohistidine in proteins.

PMID- 9570855
TI  - Reversed-phase high-performance liquid chromatographic amino acid analysis of
      phosphoproteins electroblotted onto a polyvinylidene difluoride membrane using
      dimethylaminoazobenzene sulfonyl chloride as derivatizing reagent.

PMID- 9570856
TI  - The effect of eliminating interfering substances by solid-phase extraction and
      sample-pH adjustment in the colorimetric assay of urinary nitrite and nitrate.

PMID- 9570857
TI  - Norman Cousins Memorial Lecture 1997. Stress-induced modulation of anti-viral
      immunity.

PMID- 9570858
TI  - Influence of a psychogenic and a neurogenic stressor on several indices of immune
      functioning in different strains of mice.
AB  - It is demonstrated that cell proliferation in response to mitogens, natural
      killer cell (NK) activity, and macrophage functioning of mice may be influenced
      by either a neurogenic stressor (footshock) or a psychogenic stressor (exposing
      the mouse to a predator, namely a rat). The nature and magnitude of the immune
      changes, however, varied across three strains of mice (BALB/cByJ, C57BL/6ByJ, and
      CD-1), differing in reactivity to stressors and also as a function of the type of
      stressor employed. While footshock reduced mitogen-stimulated B-cell
      proliferation in BALB/cByJ mice, it had the opposite effect in the CD-1 strain.
      Exposure to the predator, however, had little effect in any of the strains.
      Macrophage activity and NK cytotoxicity were reduced in response to both
      stressors in a strain-dependent fashion. Plasma corticosterone in response to
      footshock was greater in BALB/cByJ than in C57BL/6ByJ mice; however, the strain
      difference was not evident in response to the psychogenic stressor. It is
      suggested that analyses of stressor effects on immune functioning need to
      consider the specific strain/species employed, the particular immune parameters
      being examined, and the nature of the stressor employed.

PMID- 9570859
TI  - Restraint stress reduces the antitumor efficacy of cyclophosphamide in tumor
      bearing mice.
AB  - Treatment with the cytotoxic antitumor drug cyclophosphamide is highly effective
      in mice bearing Lewis lung carcinoma, causing the absence of macroscopically
      detectable tumors at necroscopy after sacrifice. When the effects of the
      treatment on survival are determined, a significant increase in survival time and
      in the proportion of long-term survivors is observed. When restraint stress is
      further applied, tumors develop in all of the mice treated with cyclophosphamide,
      and survival time and the fraction of long-term survivors are significantly
      reduced. Flow cytometry of splenic T-lymphocyte subsets in normal mice indicates
      a significant decrease in the number of CD3+, CD4+, and CD8+ subsets after
      treatment with cyclophosphamide and after application of restraint stress; the
      interaction of the two treatments is significant for CD3+ and marginally
      significant for CD4+ subsets. The attenuation by restraint stress which was
      observed for the effects of cyclophosphamide on the presence of tumors at
      necroscopy and for the survival of the treated mice might thus be interpreted as
      follows: restraint stress attenuates the immune functions of the host directed
      toward the weakly immunogenic tumor, an effect which, in the absence of restraint
      stress, interacts effectively with the cytotoxic action of cyclophosphamide
      toward tumor cells. The results obtained using this animal model thus indicate
      that experimental stress reduces the therapeutic efficacy of a cytotoxic
      antitumor drug; experimental and clinical implications are discussed.

PMID- 9570860
TI  - Experimental induction and termination of acute psychological stress in human
      volunteers: effects on immunological, neuroendocrine, cardiovascular, and
      psychological parameters.
AB  - The present research investigated the effects of controlled experimental
      manipulations of stress on biological and psychological reactions. Fifty young
      adult male volunteers were exposed to a 12-min period of stress induced by the
      threat of an unavoidable, painful electric shock. A 12-min period without this
      threat preceded or followed the stress period. Blood was drawn during the 4th and
      the 12th minute of each period. Anticipatory threat led to significant elevations
      in the proportions and cytotoxic activity of natural killer (NK) lymphocytes,
      plasma epinephrine levels, pulse rate, and reported level of tension, and to a
      reduction in the CD4/CD8 ratios. The no-threat period induced a return to
      baseline values for epinephrine, pulse rate, and tension, and lower than baseline
      levels for cytotoxic activity of NK lymphocytes, within a similarly short time
      span. The findings underline the rapidity with which physiological changes may
      transpire in the course of a brief and acute period of psychological stress, and
      the rapidity of their reversal upon relief from the stressor.

PMID- 9570861
TI  - The role of sympathetic innervation of the gut in regulating mucosal immune
      responses.
AB  - The effects of chemical sympathectomy on the mucosal compartments of the immune
      system were examined in adult rats. Ablation of the sympathetic nervous system
      using 6-hydroxydopamine in recipient animals reduced the migration into Peyer's
      patches and mesenteric lymph nodes (MLN) of adoptively transferred cells from MLN
      of normal donors. The mucosal immune response to ovalbumin (OVA), assessed by
      enumeration of anti-OVA antibody containing cells (AOCC) in the lamina propria
      after intestinal immunisation, was reduced in animals sympathectomized prior to
      immunization. In order to identify whether this reduction in AOCC response in
      intestinally immunized sympathectomized animals was due to a defect in migration
      of AOCC precursors to the intestinal lamina propria, the effect of chemical
      sympathectomy on the appearance of AOCC in the gut of immunized animals after
      adoptive transfer of AOCC precursors was investigated. The IgA-specific AOCC
      response was significantly reduced in sympathectomized recipients compared to the
      control group. Taken together these results demonstrate that the peripheral
      sympathetic nervous system influences the migration and accumulation in vivo of
      both naive and memory/effector lymphocytes in mucosal lymphoid tissues.

PMID- 9570862
TI  - Restraint stress slows cutaneous wound healing in mice.
AB  - The impact of stress on cutaneous wound healing was assessed in a murine model.
      Female, hairless SKH-1 mice, 6-8 weeks of age were subjected to restraint stress
      (RST) 3 days before and for 5 days following dorsal application of a 3.5-mm
      sterile punch wound. Control mice were wounded, but not restrained. Using
      photography and image analysis, the rate of wound healing was compared between
      the two groups. Wounds on control mice healed on average 3.10 days sooner than
      RST-treated mice. In addition, cross-sectional, morphometric analysis of the
      dermal and epidermal layers revealed reduced inflammation surrounding wounds from
      RST mice at 1, 3, and 5 days after wounding. In the RST group, serum
      corticosterone levels averaged 162.5 ng/ml compared to 35.7 ng/ml in the
      controls. Treatment of RST-stressed animals with the glucocorticoid receptor
      antagonist RU40555 resulted in healing rates comparable to those of control
      animals. Thus, the reduction in inflammation and delayed healing correlated with
      serum corticosterone levels and suggest that disruption of neuroendocrine
      homeostasis modulates wound healing.

PMID- 9570864
TI  - Acknowledgment
AB  - Copyright

PMID- 9570866
TI  - Predoctoral and Postdoctoral Research Fellowships
AB  - Copyright

PMID- 9570865
TI  - Brief Communications
AB  - Copyright

PMID- 9570863
TI  - Elevated cytotoxicity in combat veterans with long-term post-traumatic stress
      disorder: preliminary observations.
AB  - Resting immune [WBC and differential cell counts lymphocyte phenotyping (CD2,
      CD4, CD8, CD16, CD20, and CD56), and NK activity] and endocrine (cortisol,
      prolactin, growth hormone, and DHEA-SO4) parameters were measured in 10 male,
      Vietnam combat veterans diagnosed with long-term post-traumatic stress disorder
      (PTSD) and 9 control Vietnam combat veterans without a PTSD diagnosis but with a
      comparable history of alcohol abuse. Subjects completed a battery of
      psychological questionnaires. We report on preliminary observations of the
      relationship between PTSD and physiological and psychological parameters. With
      some important exceptions, PTSD patients did not differ from the age-matched
      control group with regard to hormone levels or lymphocyte phenotypes. However, NK
      activity was higher in the PTSD population than in the controls. Beck,
      Mississippi, and Combat Exposure scores were significantly elevated in the PTSD
      population. In contrast to previous observations in depressed populations,
      depression (indicated by elevated Beck scores), comorbid with PTSD, was
      associated with increased natural cytotoxicity.

PMID- 9570867
TI  - Discourse in Children with Neurodevelopmental Disorder, Early Focal Brain Injury,
      or Childhood Acquired Brain Injury
AB  - Copyright

PMID- 9570869
TI  - Narrative discourse in children with early focal brain injury.
AB  - Children with early brain damage, unlike adult stroke victims, often go on to
      develop nearly normal language. However, the route and extent of their linguistic
      development are still unclear, as is the relationship between lesion site and
      patterns of delay and recovery. Here we address these questions by examining
      narratives from children with early brain damage. Thirty children (ages 3:7
      10:10) with pre- or perinatal unilateral focal brain damage and their matched
      controls participated in a storytelling task. Analyses focused on linguistic
      proficiency and narrative competence. Overall, children with brain damage scored
      significantly lower than their age-matched controls on both linguistic
      (morphological and syntactic) indices and those targeting broader narrative
      qualities. Rather than indicating that children with brain damage fully catch up,
      these data suggest that deficits in linguistic abilities reassert themselves as
      children face new linguistic challenges. Interestingly, after age 5, site of
      lesion does not appear to be a significant factor and the delays we have
      witnessed do not map onto the lesion profiles observed in adults with analogous
      brain injuries.

PMID- 9570868
TI  - Discourse after early-onset hydrocephalus: core deficits in children of average
      intelligence.
AB  - A review of our studies of oral and written language in children with early-onset
      hydrocephalus suggests that hydrocephalus is associated with specific deficits in
      discourse as opposed to generalized linguistic deficit. It is proposed that the
      language skills that are impaired in hydrocephalus are those that require context
      to derive meaning, while those that are intact may function relatively
      independent of particular discourse contexts. This hypothesis was tested in two
      discourse studies comparing children with hydrocephalus of average verbal IQ to
      age-matched controls. Study 1 investigated narrative economy, syntactic
      complexity, and semantic content in the retellings of familiar and less familiar
      fairy tales. Despite producing quantities of story content similar to controls
      and using syntactic economy similar to controls, the hydrocephalus group produced
      less of the core semantic content of both familiar and less familiar tales. Study
      2 investigated inferencing and figurative language understanding in a narrative
      comprehension task. Even when prior knowledge was controlled, the hydrocephalus
      group had difficulty making inferences and recalling factual information from the
      story. In contrast to their ability to understand idiomatic figurative
      expressions, the hydrocephalus group had difficulty interpreting novel figurative
      expressions. The results are compatible with the hypothesis that the core
      discourse deficits characteristic of children with hydrocephalus are concerned
      with computing meaning from context. Putative processing features underlying the
      proposed core discourse deficit are discussed.

PMID- 9570870
TI  - Presupposition and implication of truth: linguistic deficits following early
      brain lesions.
AB  - Twenty-four children (4-17 years) with unilateral left (N = 14) or right (N = 10)
      hemisphere damage and 24 age-matched controls were tested on their ability to
      presuppose the truth of factive sentences e.g., "Max knew that he locked the
      door," and to infer the truth or falsity of implicative sentences "Max remembered
      to lock the door." Experimental sentence types varied according to the type of
      inference, the semantic features of the verb (factive vs. implicative), the
      presence and type of negation (lexical or syntactic), and the syntax of the
      complement (tensed or infinitive). Relative to age-matched controls, left lesion
      subjects were deficient in both their presupposition and implication performance,
      particularly when such inferences required the computation of negation scope.
      Right lesion subjects exhibited a somewhat more selective deficit; one limited to
      implication, but not presupposition, and one limited to lexical but not syntactic
      forms of negation.

PMID- 9570871
TI  - Children's narratives following traumatic brain injury: linguistic structure,
      cohesion, and thematic recall.
AB  - Narrative discourse and intellectual functioning were examined 3 years following
      traumatic brain injury (TBI) in children 1 to 8 years of age at the time of
      injury. The language-impaired TBI group (n = 9) had language deficits during the
      subacute stage of recovery; their performance was contrasted with that of a TBI
      comparison group equated on neurologic and demographic variables that did not
      show subacute language impairment (n = 8) and a sibling comparison group (n = 9).
      The language-impaired TBI group had lower Verbal and Full-Scale IQ scores and
      produced fewer words and utterances than the sibling group on a story retelling
      task; their stories were characterized by fewer complete referential and lexical
      ties and more referential errors, indicating difficulty conjoining meaning across
      sentences. The language-impaired TBI group recalled approximately one-third of
      the propositions needed to maintain the story theme and made more errors
      sequencing the propositions than either the TBI or the sibling comparison groups.
      Group differences were not obtained on the Performance IQ scores or on measures
      of rate or fluency of speech production, mazes, use of conjunctives, or naming
      errors. The discourse deficiencies of children with TBI and acute language
      impairment were most pronounced at the level of cognitive organization of the
      text reflecting text macrostructure and were least apparent at the level of
      lexical and sentential organization reflecting text microstructure. Results are
      discussed in terms of the vulnerability of developing language abilities to
      disruption by brain injury.

PMID- 9570872
TI  - Discourse after closed head injury in young children.
AB  - This study examined narrative discourse in 23 children, ages 6 to 8 years, who
      sustained a severe closed head injury (CHI) at least 1 year prior to assessment.
      Narratives were analyzed at multiple levels using language and information
      structure measures. Results revealed significant discourse impairments in the CHI
      group on all measures of information structure, whereas differences in the
      linguistic domain failed to reach significance. In addition, effects of age at
      injury and lateralization of lesion on discourse were considered. Although no
      significant differences were found according to age at injury, a consistent
      pattern of generally poorer discourse scores was found for the early injured
      group (< 5 years). With regard to lesion focus, the group findings were
      unimpressive. However, preliminary examination of individual CHI cases with
      relatively large lateralized lesions suggested that the late injured children may
      show the language-brain patterns reported in brain-injured adults, whereas early
      injured children may not.

PMID- 9570873
TI  - How children with head injury represent real and deceptive emotion in short
      narratives.
AB  - Narratives are not only about events, but also about the emotions those events
      elicit. Understanding a narrative involves not just the affective valence of
      implied emotional states, but the formation of an explicit mental representation
      of those states. In turn, this representation provides a mechanism that
      particularizes emotion and modulates its display, which then allows emotional
      expression to be modified according to particular contexts. This includes
      understanding that a character may feel an emotion but inhibit its display or
      even express a deceptive emotion. We studied how 59 school-aged children with
      head injury and 87 normally-developing age-matched controls understand real and
      deceptive emotions in brief narratives. Children with head injury showed less
      sensitivity than controls to how emotions are expressed in narratives. While they
      understood the real emotions in the text, and could recall what provoked the
      emotion and the reason for concealing it, they were less able than controls to
      identify deceptive emotions. Within the head injury group, factors such as an
      earlier age at head injury and frontal lobe contusions were associated with poor
      understanding of deceptive emotions. The results are discussed in terms of the
      distinction between emotions as felt and emotions as a cognitive framework for
      understanding other people's actions and mental states. We conclude that children
      with head injury understand emotional communication, the spontaneous
      externalization of real affect, but not emotive communication, the conscious,
      strategic modification of affective signals to influence others through deceptive
      facial expressions.

PMID- 9570874
TI  - Call for Papers
AB  - Copyright

PMID- 9570876
TI  - Visible changes in lesion borders on CT scan after five years poststroke, and
      long-term recovery in aphasia.
AB  - This study examined 12 aphasia patients at approximately 1 year poststroke (Time
      1) and again at 5-12 years poststroke (Time 2) with language testing and CT scan.
      Significant increases in naming scores, and phrase length in nonfluent speech
      were observed after 5 years poststroke. Significant expansion in visible lesion
      borders (lesion size) was observed after 5 years poststroke; an increase in
      lesion size of > 1% was present in 9/12 cases (75%). Not one case had a second
      stroke. Thus, it appears that even though lesion expansion may occur after 5
      years poststroke, as long as this expansion is unilateral and gradual, it has no
      adverse effect on language, and in fact, continued recovery in naming and
      nonfluent speech may also occur. Long-term recovery patterns in aphasia which may
      be associated with brain reorganization deserve further study, especially with
      functional brain imaging techniques.

PMID- 9570877
TI  - G.B. Vico, precursor of cognitive neuropsychology? The first reported case of
      noun-verb dissociation following brain damage.
AB  - The first case of selective impairment in retrieving verbs in comparison to
      nouns, following brain damage, was reported in 1744 by the Neapolitan philosopher
      G. B. Vico. He considered such observation experimental evidence of the
      correctness of his theory on mental organization of language, thus anticipating
      the methods of cognitive neuropsychology.

PMID- 9570878
TI  - Hemispheric priming in a reading task.
AB  - Some theories of reading and of reading disorders assume that the right
      hemisphere plays an important role in reading. However, despite the evidence
      supporting the competence of the right hemisphere in recognizing isolate words,
      there is little direct evidence to support the claim that the right hemisphere is
      involved in the continuous reading of connected text. This study used a
      stationary window technique to present text passages in a continuous reading
      task. At intervals during the reading of the text, a lexical decision was
      required to a target projected to the left or right side of the visual field. On
      some trials, the target was primed by a semantic associate which appeared in the
      passage immediately prior to the presentation of the target. It was found that
      these associative primes facilitated responses to LVF and RVF targets to an equal
      degree. It was also found, in agreement with previous investigations, that
      overall RTs to LVF targets were longer than RTs to RVF targets. It is suggested
      that these results indicate that the right hemisphere is actively involved in the
      comprehension of text in normal reading. However, the right hemisphere may not
      acquire text information directly, but may instead receive most of its
      information following initial analysis and decoding by the left.

PMID- 9570879
TI  - Temporal lobe asymmetry and dyslexia: an in vivo study using MRI.
AB  - Three measures of the right and left temporal lobes were taken with magnetic
      resonance imaging (MRI) in groups of dyslexics (N = 17), retarded readers (N =
      6), and normal controls (N = 12). The most pronounced differences among the
      groups were found with measures on coronal slices of the cross sectional area of
      the temporal cortex with subcortical white matter--in particular lateral to
      insula. While most of the normal and the retarded readers (13 of 18) had left
      asymmetry (left area larger than right), most of the dyslexics (14 of 17) had
      symmetry or right asymmetry. The degree of left asymmetry, (L-R)/[0.5(L + R)],
      was found to correlate with both reading skills and skills in phonemic analysis
      of spoken language. These results were also found when differences in non-verbal
      IQ were accounted for. The implications for definitions of dyslexia, for
      psycholinguistic research on dyslexia, and for remedial teaching are discussed.

PMID- 9570880
TI  - Conduction aphasia in a 3-year-old with a left posterior cortical/subcortical
      abscess.
AB  - A 3-year-old, right-handed girl developed a conduction-type aphasia following a
      second generalized seizure in the setting of a developing abscess involving left
      subcortical and cortical angular gyrus and arcuate fasciculus, and the posterior
      corpus callosum. The language disorder was fluent, characterized by age
      appropriate mean length of utterance and syntax, but with markedly reduced
      spontaneity of output, rapid rate of speech and mild dysarthria. Comprehension
      was relatively, but not completely spared. Naming, repetition, and reading
      (letters) were initially markedly impaired. Improvements in naming and repetition
      were associated with both literal and semantic paraphasias. Writing skills in the
      form of drawing were spared, but a mild apraxia to verbal command and imitation
      was initially present. Despite her young age, this child's fluent conduction
      aphasia and lesion localization were adult-like. Multimodal memory difficulties
      appeared to underlie what is best described as conduction aphasia.

PMID- 9570881
TI  - Distinguishing lies from jokes: theory of mind deficits and discourse
      interpretation in right hemisphere brain-damaged patients.
AB  - Right-hemisphere brain damaged (RHD) patients and a normal control group were
      tested for their ability to infer first- and second-order mental states and to
      understand the communicative intentions underlying ironic jokes and lies.
      Subjects listened to stories involving a character who had either a true or a
      false belief about another character's knowledge. Stories ended either with an
      ironic joke or a lie by this character. In the joke stories, the speaker knew
      that the listener knew the truth (a true second-order belief) and did not expect
      the listener to believe what was said; in the lie stories, the speaker did not
      know that the listener actually knew the truth (a false second-order belief) and
      thus did expect the listener to believe what was said. RHD patients performed
      significantly worse than control subjects on one of two measures of second-order
      belief, which suggests that the ability to make second-order mental state
      attributions is fragile and unreliable following right-hemisphere damage. RHD
      patients in addition performed worse than controls when asked to distinguish lies
      from jokes, confirming their known difficulties with discourse interpretation.
      For both groups, the ability to distinguish lies from jokes was strongly
      correlated with two measures of the ability to attribute correctly second-order
      beliefs. These results suggest that the fragility of RHD patients' understanding
      of second-order mental states underlies a portion of their difficulties in
      discourse comprehension, but that the underlying impairment is not restricted to
      right hemisphere dysfunction.

PMID- 9570882
TI  - Gesture and the processing of speech: neuropsychological evidence.
AB  - Patterns of speech-related ('coverbal') gestures were investigated in three
      groups of right-handed, brain-damaged patients and in matched controls. One group
      had anomic aphasia with a primarily semantic impairment ('semantic'); one group
      had a primarily phonological impairment, reflected in both repetition and naming
      ('phonologic'); a third group had a primarily conceptual impairment, with
      relatively good naming ('conceptual'). Coverbal gestures were video recorded
      during the description of complex pictures and analyzed for physical properties,
      timing in relation to speech and ideational content. The semantic and phonologic
      subjects produced a large number of ideational gestures relative to their lexical
      production, while the related production of the conceptual subjects was similar
      to that of the unimpaired controls. The composition of ideational gestures in the
      semantic and phonologic groups was similar to that of the control groups, while
      conceptual subjects produced fewer iconic gestures (i.e., gestures that show in
      their form the content of a word or phrase). The iconic gestures of the
      conceptual patients tended to start further from their lexical affiliates than
      those of all other subjects. We conclude that ideational gestures probably
      facilitate word retrieval, as well as reflect the transfer of information between
      propositional and non-propositional (visual and motoric) representations during
      message construction. We suggest that conceptual and lexical processes differ in
      the way they constrain ideational gestures.

PMID- 9570885
TI  - NEW NORTH AMERICAN EDITOR OF CBI -DR BECHARA KACHAR

PMID- 9570883
TI  - Abnormal callosal morphology in male adult dyslexics: relationships to handedness
      and phonological abilities.
AB  - The classical notion that developmental dyslexia may somehow relate to impaired
      communication between hemispheres has not yet received convincing support.
      Sixteen dyslexic adults and 12 controls received a high resolution brain MRI scan
      for morphometric study of the corpus callosum. Automatized measurements of
      callosal area and calculation of indices defining the general morphology of the
      callosal mid-surface were performed. Each participant received global
      intelligence and reading achievement evaluation; dyslexics were further proposed
      specific neuropsychological tests specially designed to explore the mechanisms of
      reading impairment. It just appears from the group comparisons (1) that the
      dyslexics' corpus callosum displays a more circular and evenly thicker general
      shape, and (2) that the midsagittal surface is on the average larger than in
      controls, in particular in the isthmus. Moreover, the different morphometric
      characteristics of the dyslexic brain correlated with the degree of impairment on
      various tests exploring phonological abilities. In vivo morphometry of the corpus
      callosum may provide valuable hints for understanding developmental learning
      disorders and their consequences in adults.

PMID- 9570886
TI  - ASSISTANCE IN MANUSCRIPT PRESENTATION

PMID- 9570888
TI  - Major laminin-binding and F-actin-linked glycoproteins of neutrophils.
AB  - Two major EHS-laminin-binding membrane glycoproteins--with apparent molecular
      masses of 50 kD and 18 kD--were shown by protein blotting in membrane fractions
      of porcine neutrophils. These galectin-like glycoproteins (binding probably via
      the N-acetyllactosamine sequences to laminin) could also be detected by labelled
      F-actin in protein blots. Following 35 min adhesion to the plastic surface, the
      relative amount of the 18 kD protein increased considerably in the light (plasma
      membrane) and in the dense (intracellular) membrane fractions of the attached
      cells; the 50 kD polypeptide (identified as a CD14-like protein) seemed to
      accumulate characteristically in the dense membrane fraction. These observations
      imply that direct connections could be formed between membrane glycoproteins and
      microfilaments during cell-substrate adhesion which may be preceded by enhanced
      cell surface targeting of certain adhesion receptors.

PMID- 9570889
TI  - Intercellular communication in rapidly proliferating and differentiated C6 glioma
      cells in culture.
AB  - Glial cells in the brain are known to provide structural and functional supports
      to neurons. To sustain such a supportive role, they have developed cell-to-cell
      communicating gap junctional channels. The authors studied the effect of dbcAMP
      on gap junctional channels mediated communication in C6 cells, a rat glioma cell
      line. Quantitative assessment of coupled cells under microscope after
      microinjection of a fluorescent dye was taken as a measure of junctional
      permeability. An enhanced coupling between cells was observed following dbcAMP
      treatment and this elevated coupling was found to be dependent on the duration of
      exposure of cells to dbcAMP. The studies have focused on a subtle shift in the
      spatial organization of the functional channels to the processes of dbcAMP
      induced differentiated cells from the cell cytoplasms and membranes of dbcAMP
      untreated cells. Immunofluorescence study with affinity purified antibody against
      gap junction further confirmed the spatial distribution of gap junctional
      protein(s) in the processes and also showed an increase in the density of the
      protein at the intercellular spaces in dbcAMP induced differentiated C6 glioma
      cells.

PMID- 9570890
TI  - The influence of dose fractionation on radiation-induced haemolysis of human
      erythrocytes.
AB  - In this paper the radioresistance of human erythrocytes to radiation-induced
      haemolysis was studied by means of the split-dose technique. Human erythrocytes
      suspended in an isotonic Na-phosphatase buffer, pH 7.4 were exposed under air to
      gamma radiation. Erythrocytes were irradiated with a single dose of 2.7 kGy and
      with the same total dose split into two fractions with an interval between the
      subsequent exposures. It seems that postradiation processes initiated by the
      first radiation dose of definite magnitude can lead to an increase in the
      resistance of erythrocytes to haemolysis under the influence of subsequent dose.
      The maximal effect of the fractionation (50% decrease of haemolysis) was observed
      when the first fraction was equal to 0.3-0.4 kGy and the interval between
      exposures was equal to 3 h.

PMID- 9570891
TI  - ADHESION-DEPENDENT F-ACTIN PATTERN IN AMOEBA PROTEUS AS A COMMON FEATURE OF
      AMOEBAE AND THE METAZOAN MOTILE CELLS
AB  - Adhesion and movement of Amoeba proteus are both dependent on the appropriate
      arrangement of the F-actin cytoskeleton and on the presence of the cell nucleus.
      In this study the F-actin organization was examined by routine FITC-phalloidin
      staining and confocal laser microscopy in intact amoebae and in their nucleated
      and anucleated fragments, at different levels of cell adherence to the
      substratum. In the adhering and migrating intact cells and nucleated cell
      fragments dot-like aggregates of F-actin are scattered over the ventral side at
      sites close to the substratum. In the case of de-adhesion of nucleated specimens
      this pattern disappears and F-actin is accumulated in the cell centre and/or
      dispersed in the cytoplasm. The same actin distribution, without ventral dots, is
      found in the anucleated fragments which usually fail to attach to the substratum.
      Re-adhesion of anucleated fragments, induced by a modified substratum or
      spontaneous, is accompanied by restoration of actin dots at the lower cell side.
      It is concluded that: (1) adhering specimens of A. proteus display the same dot
      like actin pattern on the ventral cell side, as many metazoan motile cells; (2)
      organization or disorganization of this pattern may occur independently of the
      presence of the cell nucleus, under the control of cell adhesion to the
      substratum. Copyright 1998 Academic Press Limited

PMID- 9570892
TI  - Histochemistry of oxidases in several tissues of bivalve molluscs.
AB  - Various tissues of the marine bivalve Mytilus galloprovincialis were analysed
      histochemically for oxidases capable of generating reactive oxygen species (ROS)
      using the cerium-DAB technique. Incubations were performed on unfixed cryostat
      sections using polyvinyl alcohol and semipermeable membranes. High xanthine
      oxidoreductase and D-amino acid oxidase (DAOX) activities were observed in kidney
      epithelial cells of mussels. DAOX also presented a strong activity in all the
      digestive epithelia. No xanthine oxidase activity was observed in any of the
      mussel tissues tested suggesting the presence of an enzyme only showing
      dehydrogenase activity. Mannitol oxidase, associated with special organelles
      called 'mannosomes' of terrestrial gastropods, presented a weak activity in the
      stomach epithelium and a strong specific activity in the haemocytes. Only DAOX
      presented a discrete granular distribution compatible with a peroxisomal
      compartmentalization. No urate oxidase activity could be demonstrated in tissues
      of mussels. These observations suggest a role for peroxisomes in ROS generation
      and determine the tissues capable of producing oxygen radicals in the digestive
      gland. This study raises the question of the behaviour of these enzymes in
      conditions in which ROS-generating organic xenobiotics are accumulated in the
      digestive gland of molluscs.

PMID- 9570893
TI  - Inhibition of phenotype modulation, growth, and migration of vascular smooth
      muscle cells by a guanosine-rich 30-mer phosphorothioate oligodeoxynucleotide.
AB  - The testing of a 30-mer dG-rich phosphorothioate oligodeoxynucleotide (LG4PS) for
      effects on the behaviour of vascular smooth muscle cells (VSMC) in vitro and in
      vivo is described. LG4PS at 0.3 microM inhibited significantly the phenotype
      modulation of freshly isolated rabbit VSMC, and cell outgrowth from pig aortic
      explants was inhibited approximately 80% by 5 microM LG4PS. The growth of
      proliferating rabbit and pig VSMC was inhibited approximately 70% by 0.3 microM
      and 5 microM LG4PS, respectively. Though less marked, the antiproliferative
      effects of LG4PS on human VSMC were comparable to those obtained with heparin.
      The cytotoxic effects of LG4PS on VSMC in vitro were low. Despite these promising
      results, adventitial application of 2-200 nmol LG4PS in pluronic gel failed to
      reduce vascular hyperplasia in balloon-injured rabbit carotid arteries, and the
      highest dose caused extensive mortality.

PMID- 9570894
TI  - RolB expression pattern in the early stages of carrot somatic embryogenesis.
AB  - The pattern of expression of the rolB gene, derived from the T-DNA of the plant
      pathogen Agrobacterium rhizogenes, has been investigated during the early stages
      of somatic embryo formation in suspension cultures of carrot (Daucus carota L.).
      The reporter gene GUS (Escherichia coli beta-glucuronidase), under
      transcriptional control of full-length rolB promoter region, has been utilized in
      order to evaluate both qualitative and quantitative variations in the expression
      pattern. Fluorimetric measurements point to the developmental regulation of the
      gene, while results from histochemical analysis indicate that the promoter of
      rolB is firstly activated in the central (core) region of the globular embryos.

PMID- 9570895
TI  - Inhibition of lactogenic activities of bovine mammary gland explants by the whey
      fraction of bovine milk.
AB  - The regulation of milk constituents, synthesis and secretion in tissue cultures
      of the bovine mammary gland was altered by a whey fraction of bovine milk. alpha
      Casein gene expression, casein secretion and fatty acid synthesis were inhibited
      by the whey fraction in a dose-dependent manner. The whey fraction inhibited the
      enhancement activity of prolactin on alpha-casein gene expression and fatty acid
      synthesis, and also inhibited casein secretion to the medium, in explants
      cultured in a medium with or without prolactin. No effect on the expression of
      the beta-lactoglobulin gene was found.

PMID- 9570897
TI  - Adding apples and oranges: alignment of semantic and formal knowledge.
AB  - We show that the same mechanism that mediates analogical reasoning (i.e.,
      structural alignment) leads to interpretive "content effects" in reasoning about
      arithmetic word problems. Specifically, we show that both college students and
      textbook writers tend to construct arithmetic word problems that maintain
      systematic correspondence between the semantic relations that people infer from
      pairs of real-world objects (e.g., apples and baskets support the semantic
      relation CONTAIN [content, container]) and mathematical relations between
      arguments of arithmetic operations (e.g., DIVIDE [dividend, divisor]). Such
      relational alignments, to which we refer here as semantic alignments, lead to
      selective and sensible application of abstract formal knowledge. For example,
      people usually divide apples among baskets rather than baskets among apples, and
      readily add apples and oranges but refrain from adding apples and baskets.

PMID- 9570896
TI  - Decrease in elastin gene expression and protein synthesis in fibroblasts derived
      from cardinal ligaments of patients with prolapsus uteri.
AB  - Abnormal connective tissues may be a key factor in the development of pelvic
      supportive disorders. Elastin gene transcripts and elastin synthesis in cultured
      fibroblasts derived from cardinal ligaments of patients with prolapsus uteri and
      compared them with those in fibroblasts from age-matched control patients were
      examined. Elastin mRNA steady-state levels and elastin synthesis were
      significantly down-regulated in quiescent fibroblasts from prolapsus uteri
      patients compared with quiescent control fibroblasts. Although transforming
      growth factor beta 1 (TGF-beta 1) promoted elastin mRNA and protein levels in
      fibroblasts from both prolapsus uteri and control patients, the maximum levels of
      elastin gene transcripts and elastin synthesis in response to exogenous TGF-beta
      1 were significantly lower in prolapsus uteri fibroblasts than control
      fibroblasts. These results suggest that the marked reduction in elastin gene
      transcripts and elastin production in fibroblasts cultured from elderly women
      with prolapsus uteri could lead to a paucity of ligament elastic fibres and thus
      may contribute to the loss of supportive function in uterine connective tissues.

PMID- 9570898
TI  - On the relations among different measures of visible and informational
      persistence.
AB  - We report research designed to accomplish two goals. We first consider the
      question, raised by Coltheart (1980) and others, of whether three measures of
      visible and informational persistence--performance in temporally integrating two
      successively presented stimuli, subjective rating of the degree to which two
      successively presented stimuli appear to constitute a single or a dual temporal
      event, and partial-report performance--all measure the same underlying mental
      entity. We answer this question using a superset of dissociation logic called
      state-trace analysis (Bamber, 1979), and within the context of a systematic
      empirical foundation consisting of seven closely related experiments. Our second
      goal is to extend and apply a theory to data acquired from our seven experiments
      and also to data reported by other investigators. This theory, which has been
      confirmed in a variety of paradigms (see Busey & Loftus, 1994) assumes that (1)
      the initial stages of the visual system act as a low-pass linear filter which
      operates on a stimulus temporal waveform to produce a sensory response; (2)
      instantaneous rate of acquiring information from the stimulus is jointly
      proportional to sensory-response magnitude and proportion of as-yet-to-be
      acquired stimulus information; (3) partial-report performance is determined by
      total amount of acquired information; (4) the probability that two events are
      perceived as contemporaneous is determined by the temporal correlation of their
      respective information-acquisition rate functions (which is similar to a
      suggestion by Dixon & Di Lollo, 1994); and (5) temporal integration is successful
      to the degree that the two temporal events are perceived as contemporaneous. This
      theory was highly successful in accounting for our and other investigators'
      temporal-integration and completeness-rating data, and was moderately successful
      in accounting for partial-report data. We discuss the degree to which our three
      persistence measures can be united within the context of our theory; we comment
      on the distinction between objective and subjective measures of visible
      persistence; and we address the decades-old question: "What is persistence good
      for?"

PMID- 9570899
TI  - DerivFit: a program for rate equation parameter fitting using derivatives.
AB  - A C program for fitting parameters in enzymatic rate equations is presented. The
      DerivFit program employs the reaction scheme in the form of ordinary differential
      equations (ODEs). The kinetic parameters are fitted to the experimental data by
      minimizing the sum of squared deviations of experimental points from
      theoretically predicted progress curves. In the minimization process we use the
      Gradient, Newton, and Marquardt algorithms. The gradients are calculated
      explicitly by solving a set of additional ODEs that are automatically attached by
      the program, taking advantage of a general formulation of the basic ODEs that
      determine the reaction's time course. The program is applied to simple enzymatic
      systems including slow tight-binding inhibition.

PMID- 9570900
TI  - Computer-assisted analysis of the impact of respiratory quotient on blood CO2
      tension and pH changes.
AB  - A computer model for the accurate quantification of blood gas exchange components
      was used to assess the impact of respiratory quotient (RQ) on venoarterial CO2
      tension and pH differences over a large group of patient measurements. The
      combined use of measured and computer-generated data has shown that, for any
      given increase in blood CO2 concentration (i.e., when the arterial blood becomes
      venous), the associated increase in CO2 tension and decrease in pH are inversely
      related to the RQ, and that this relationship is mediated by the Haldane effect.
      These results are useful for a through understanding of blood gas and metabolic
      interactions in normal and abnormal states, and for improving the interpretation
      of changes in venoarterial CO2 tension gradient in clinical monitoring.

PMID- 9570901
TI  - Contribution to the definition of the power bands limits of sleep EEG by linear
      prediction.
AB  - The linear prediction method has been applied to compute the power spectra
      distribution in 10 healthy young men (aged 17 to 26). For each subject, the local
      extrema positions have been detected and grouped as a function of their
      frequency. The computation of a mean frequency distribution for the extrema
      position, on the 10 subjects, allowed for the definition of eight frequency power
      bands. The time evolution of these power bands during the first NREM episode has
      been computed and averaged for the 10 subjects. The cross-correlation analysis
      demonstrated the relevance of three bands in the range 0-8.10 Hz: delta ]0-2.78]
      Hz, theta 1 ]2.78-5.42] Hz, theta 2 ]5.42-8.10] Hz. Our extrema study leads to
      the division of the beta range ]16.25-25.00] Hz into three bands. However, their
      time evolution does not support the usefulness of the partitioning of the beta
      range, probably resulting from our too low sampling frequency.

PMID- 9570902
TI  - Developing online support for clinical information system developers: the FAQ
      approach.
AB  - OBJECTIVE: We investigate a knowledge-based help system for developers of an
      integrated clinical information system (CIS). The first objective in the study
      was to determine the system's ability to answer users' questions effectively.
      User performance and behavior were studied. The second objective was to evaluate
      the effect of using questions and answers to augment or replace traditional
      program documentation. DESIGN: A comparative study of user and system
      effectiveness using a collection of 47 veritable questions regarding the CIS,
      solicited from various CIS developers, is conducted. Most questions were
      concerning the clinical data model and acquiring the data. MEASUREMENTS: Answers
      using current documentation known by users were compared to answers found using
      the help system. Answers existing within traditional documentation were compared
      to answers existing within question-answer exchanges (Q-A's). RESULTS: The
      support system augmented 39% of users' answers to test questions. Though the Q
      A's were less than 5% of the total documentation collected, these files contained
      answers to nearly 50% of the questions in the test group. The rest of the
      documentation contained about 75% of the answers. CONCLUSIONS: A knowledge-based
      help system built by collecting questions and answers can be a viable alternative
      to large documentation files, providing the questions and answers can be
      collected effectively.

PMID- 9570903
TI  - Detection of spikes with artificial neural networks using raw EEG.
AB  - Artificial neural networks (ANN) using raw electroencephalogram (EEG) data were
      developed and tested off-line to detect transient epileptiform discharges (spike
      and spike/wave) and EMG activity in an ongoing EEG. In the present study, a
      feedforward ANN with a variable number of input and hidden layer units and two
      output units was used to optimize the detection system. The ANN system was
      trained and tested with the backpropagation algorithm using a large data set of
      exemplars. The effects of different EEG time windows and the number of hidden
      layer neurons were examined using rigorous statistical tests for optimum
      detection sensitivity and selectivity. The best ANN configuration occurred with
      an input time window of 150 msec (30 input units) and six hidden layer neurons.
      This input interval contained information on the wave component of the
      epileptiform discharge which improved detection. Two-dimensional receiver
      operating curves were developed to define the optimum threshold parameters for
      best detection. Comparison with previous networks using raw EEG showed
      improvement in both sensitivity and selectivity. This study showed that raw EEG
      can be successfully used to train ANNs to detect epileptogenic discharges with a
      high success rate without resorting to experimenter-selected parameters which may
      limit the efficiency of the system.

PMID- 9570904
TI  - Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to several ecological receptor
      groups: a short review.
AB  - Toxicity among TCDD isomers can vary significantly. Isomers containing four to
      six chlorine atoms possess the greatest potential for biological activity, as
      well as the highest acute toxicity. Information available in the literature
      focuses largely on fish and terrestrial mammal studies. Toxicity data for aquatic
      invertebrates and plants is wanting, and essentially no studies pertaining to
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) accumulation in these organisms could
      be found. No data were procurable regarding TCDD toxicity in marine mammals or
      reptiles. Current knowledge is not sufficient to accurately characterize TCDD
      toxicity in ecological receptors, with quantification of uncertainty being
      particularly difficult given the limited base of knowledge.

PMID- 9570905
TI  - Evaluation of the toxicity of guarana with in vitro bioassays.
AB  - A natural stimulant, Paullinia cupana, commonly called guarana, was tested for
      its ability to induce in vitro toxicity in Chinese hamster ovary (CHO) cells and
      bacterial cells (Photobacterium phosphoreum). The cytotoxic effects of aqueous
      guarana extracts were evaluated by three endpoint systems: neutral red (NR)
      uptake assay, total protein content [kenacid blue (KB)] assay, and tetrazolium
      (MTT) assay. The Microtox test was also used. Results indicated that the lowest
      concentration of guarana tested was not toxic and that the IC50 values calculated
      with the NR, KB, and MTT assays were lower than the highest concentration tested
      (40 mg/ml). There was no significant difference in cytotoxicity between the three
      test systems. The EC50 values obtained with the Microtox assay were consistent
      with these data. The present in vitro analysis suggests that the concentration of
      guarana is of critical importance in its cytotoxic activity and high doses could
      be harmful to human health.

PMID- 9570906
TI  - Reference values of 5-aminolevulinate dehydrase and porphobilinogen deaminase in
      the Spanish population from Madrid.
AB  - 5-Aminolevulinate dehydrase (ALA-D) and porphobilinogen deaminase (PBG-D) are
      cytosolic enzymes involved in heme biosynthesis. ALA-D activity is altered both
      genetically and by the action of various environmental factors, including
      exposure to lead. The activity of PBG-D is reduced in acute intermittent
      porphyria. The aim of this work is to establish the 95% reference range of the
      erythrocytic activity of ALA-D and PBG-D in a control population. ALA-D activity
      limits were 15.8 and 50.2 nmol of PBG/ml of red blood cells (RBCS) per minute.
      For the activity of ALA-D restored by addition of zinc and dithiothreitol
      ("restored ALA-D"), these limits were 44.1 and 86.5 units. It has been found that
      the "restored ALA-D"/ALA-D ratio is very useful for the evaluation of lead
      toxicity, and its 95% reference range was between 1.22 and 3.06. It has been
      demonstrated that the best method for measuring erythrocytic PBG-D is using PBG,
      but not ALA, as substrate; its 95% reference range was between 20.9 and 63.2 nmol
      of uroporphyrin/ml of RBCs per hour. Knowledge of these reference range values in
      a control population constitutes the basis for an accurate diagnosis of heavy
      metal intoxication and acute intermittent porphyria.

PMID- 9570907
TI  - Toxicity and bioaccumulation of lead in marine protozoa communities.
AB  - The toxicity and bioaccumulation of lead has been studied using marine protozoa
      communities developed in laboratory microecosystems. The concentrations tested
      were 500 and 1000 micrograms.L-1 of lead as lead acetate. The protozoan was able
      to bioaccumulate 27.02-504 micrograms Pb.g-1 dry weight. Bacteria also
      bioaccumulated lead, but always to a lesser degree than protozoa. Lead caused a
      significant reduction in the density of protozoa, which could be an indirect
      response to the cellular increase of lead. On the other hand, the toxicant did
      not determine a decrease in the number of bacterial cells; this could be due to
      their capacity to bioaccumulate a lesser amount of lead, the increase in the
      number of dead cells, and the elimination of their predators by the toxicant.
      After 120 h, a recovery of the community was observed.

PMID- 9570908
TI  - Correlation between the levels of certain carcinogenic and anticarcinogenic trace
      elements and esophageal cancer in northern Iran.
AB  - Levels of four carcinogenic (Ni, Fe, Cu, Pb) and four anticarcinogenic (Zn, Se,
      Mn, Mg) trace elements were measured in hair samples from esophageal cancer
      patients, their unaffected family members, and members of families with no
      history of cancer. Measurements were also made in non-esophageal cancer patients,
      using atomic absorption spectroscopy, inductively coupled plasma-emission
      spectroscopy, and neutron activation analysis. The results showed that Ni and Cu
      concentrations were significantly higher and Mg and Mn concentrations were
      significantly lower in all cancer cases. Levels of Zn, Fe, Se, and Pb were not
      significantly different in the above-mentioned groups. In addition, the serum
      albumin fraction, which is reported to have antioxidant activity, was found to be
      significantly lower among esophageal cancer patients.

PMID- 9570909
TI  - Development of a soil extraction procedure for ecotoxicity characterization of
      energetic compounds.
AB  - The acetonitrile-sonication extraction method (US EPA Method 8330) associated
      with aquatic-based toxicity tests was examined to study the ecotoxicity of
      energetic substances in soil. Three studies were carried out: (1) toxicological
      characterization of different energetic substances to select a representative
      toxicant and to validate the choice of bioassays; (2) choice of an appropriate
      solvent to transfer acetonitrile extracts to the bioassay incubation media; and
      (3) optimization of Method 8330 using soil samples spiked with the toxicant.
      Initial studies indicated that pure 2,4,6-trinitrotoluene (TNT) was toxic to
      Vibrio fischeri [Microtox; IC50 (15 min) of 4.2 microM], whereas RDX was less
      toxic (IC20 = 181 microM) and HMX was not toxic up to its limit of water
      solubility (< 22 microM). Selected pure TNT metabolites were less toxic than TNT.
      Similar results were found using the 96-h Selenastrum capricornutum growth
      inhibition test. The toxicity of pure TNT in different solvents (acetonitrile,
      acetone, and DMSO) and that from Method 8330-extracted TNT-spiked soil samples
      were compared to TNT dissolved in water. Data indicated that DMSO was the most
      appropriate solvent to transfer the acetonitrile extracts. A modified Method 8330
      may be used in conjunction with bioassays and chemical analyses to examine the
      ecotoxicity of soils contaminated with energetic substances.

PMID- 9570910
TI  - Comparisons of acute toxicity of selected chemicals to rainbow trout and rats.
AB  - Median lethal concentration (LC50) and dose (LD50) for 217 chemicals were
      compared over several exposure routes in rainbow trout and rats. Data were
      compiled primarily from on-line databases and included octanol-water partition
      coefficient (Kow), trout LC50, and trout and rat LD50 for oral, dermal, and
      intraperitoneal (i.p.) routes. Kow and molar lethality data were log-transformed
      for correlation and regression analyses. Median ratios (rat oral LD50/trout LC50
      = 156, rat/trout oral LD50 = 0.80, rat/trout dermal LD50 = 0.43, rat/trout i.p.
      LD50 = 0.55) demonstrated the effect of similar versus dissimilar exposure routes
      on lethality, reflecting toxicokinetic differences. Simple linear regressions
      revealed significant correlations (Bonferroni P < 0.05) for trout LC50 versus rat
      oral LD50 and for trout LD50 versus rat LD50 when matched on exposure route. When
      Kow was included with multiple regression to consider the effect of
      hydrophilic/lipophilic partitioning on uptake and toxicity, correlations improved
      only for trout LC50 versus rat oral LD50 and for trout i.p. LD50 versus rat i.p.
      LD50. Stratification of data into pesticides and nonpesticides failed to refine
      prediction of trout LC50 from rat oral LD50. Simple regressions reported here and
      in the literature relating fish LC50 and rat oral LD50 exhibited varying degrees
      of correlation (r = 0.26-0.99), reflecting differences in interspecies
      sensitivity, chemical group evaluated, and experimental methodologies.

PMID- 9570911
TI  - Evaluation of a high-hardness COMBO medium and frozen algae for Daphnia magna.
AB  - A new high-hardness (H-H) COMBO medium for long-term culturing and bioassay
      testing of Daphnia magna was evaluated in 21-day survival, growth, and
      reproduction studies. The COMBO medium originally designed for softwater daphnid
      species (i.e., D. pulicaria) was modified for the hardwater species D. magna.
      This medium also allowed continuous culturing of a green algal food source for
      daphnids, Ankistrodesmus falcatus. After 12 generations of culturing in H-H COMBO
      medium, the mean fecundity was 128 +/- 12 (coefficient of variation = 9.4%). No
      significant observations of dead young, aborted eggs, or reduced antennas were
      made during the 6 months of continuous culturing. The no-observable-effect
      concentration (NOEC) for a reference toxicant standard, 3,4-dichloroaniline (3,4
      DCA), was 8.3 micrograms/liter, which is similar to published values. These
      studies demonstrate that H-H COMBO is an acceptable medium for use for culturing
      and bioassay testing with D. magna. Additional experiments using frozen aliquots
      of A. falcatus were conducted. Although mean fecundity (64 +/- 7) and adult
      length were significantly decreased from the values for daphnids fed fresh algae,
      the NOEC for 3,4-DCA was > 25 micrograms/liter. The use of this alternative food
      source in bioassay testing appears promising, but further optimization of feeding
      rates is warranted.

PMID- 9570912
TI  - Distribution of free seleno-amino acids in plant tissue of Melilotus indica L.
      grown in selenium-laden soils.
AB  - Accumulation of specific groups of seleno-amino acids in plant tissue reflects
      not only the Se tolerance of a plant species, but also Se toxicity to animals.
      The distribution of seleno-amino acids in a Se-tolerant grassland legume species
      (Melilotus indica L.) grown in Se-laden soils was studied using high-resolution
      gas chromatography- and gas chromatography-mass spectrometry. Five seleno-amino
      acids including selenocystine, selenomethionine, selenocysteine, Se
      methylselenocysteine, and gamma-glutamyl-Se-methylselenocysteine were identified
      and measured for their plant tissue concentrations. Se-methylselenocysteine, a
      nonprotein seleno-amino acid, was found in the plant tissue. Its concentration
      ranged from 15.3 mumol kg-1 for the plants growing in soil of low Se
      concentration to 109.8 mumol kg-1 for the plants grown in soil of high Se
      concentration. Accumulation of the nonprotein seleno-amino acid in this species
      resembles that in Se accumulator plants. gamma-Glutamyl-Se-methylselenocysteine
      was detected in the plant. However, its concentration was very low. It might not
      become a toxic element in the food chain. Results of plant tissue Se accumulation
      analysis indicated that there was a five-fold increase in tissue selenocysteine
      concentration when the total tissue Se increased from 5.07 to 22.02 mg kg-1, but
      there was no further increase in tissue selenocysteine concentration when the
      tissue total Se concentration increased from 22.0 to 117.4 mg kg-1.
      Selenomethinone constituted more than 50% of the total seleno-amino acid in the
      plant. More research is needed to reveal whether the mechanisms limiting the
      accumulation of selenocysteine and preferential accumulation of selenomethionine
      found in this study play any role in Se tolerance in this species.

PMID- 9570913
TI  - Ground and surface water developmental toxicity at a municipal landfill:
      description and weather-related variation.
AB  - Contaminated groundwater poses a significant health hazard and may also impact
      wildlife such as amphibians when it surfaces. Using FETAX (Frog Embryo
      Teratogenesis Assay-Xenopus), the developmental toxicity of ground and surface
      water samples near a closed municipal landfill at Norman, OK, were evaluated. The
      groundwater samples were taken from a network of wells in a shallow, unconfined
      aquifer downgradient from the landfill. Surface water samples were obtained from
      a pond and small stream adjacent to the landfill. Surface water samples from a
      reference site in similar habitat were also analyzed. Groundwater samples were
      highly toxic in the area near the landfill, indicating a plume of toxicants.
      Surface water samples from the landfill site demonstrated elevated developmental
      toxicity. This toxicity was temporally variable and was significantly correlated
      with weather conditions during the 3 days prior to sampling. Mortality was
      negatively correlated with cumulative rain and relative humidity. Mortality was
      positively correlated with solar radiation and net radiation. No significant
      correlations were observed between mortality and weather parameters for days 4-7
      preceding sampling.

PMID- 9570914
TI  - The acute toxicity of selected alkylphenols to young and adult Daphnia magna.
AB  - Differences in sensitivity toward toxicants between young and adult individuals
      in a population are assumed to be primarily associated with their difference in
      body size. This assumption plays a key role in the modeling of effects of
      variable concentrations of toxicants on nonhomogeneous populations. The hazard
      based no-effect-concentrations (NECs), killing rates, and elimination rates,
      estimated from the survival data of a series of acute toxicity tests with young
      and adults of Daphnia magna and six alkylphenols, were used to evaluated this
      assumption. The results lead to the conclusion that young and adult D. magna were
      equally sensitive in terms of NEC and killing rate and that the observed
      differences in elimination rates could be explained on the basis of a difference
      in body size. Furthermore, it was found that elimination rates estimated on the
      basis of the survival data were consistently smaller than those expected on the
      basis of a QSAR for Daphnia pulex, a comparable species. This discrepancy was
      likely due to a decreased uptake and elimination during a period of
      immobilization prior to death. Since it is unknown to what extent immobilized
      individuals are able to recover from short-term exposures, the observed deviation
      clearly identifies a complicating factor in the modeling of effects of variable
      concentrations of toxicants.

PMID- 9570915
TI  - A simple immunomagnetic protocol for the selective isolation and long-term
      culture of human dermal microvascular endothelial cells.
AB  - Endothelial cells involved in tumor angiogenesis, wound healing, and inflammation
      are predominantly of microvascular origin and are functionally distinct from
      large vessel-derived endothelial cells which have been largely used for in vitro
      vascular research. To overcome the problems commonly involved in the culture of
      microvascular endothelial cells, including unreliable isolation techniques and
      low cell yields, we developed a simplified protocol for the selective cultivation
      of human dermal microvascular endothelial cells (HDMEC) obtained from neonatal
      foreskins, based on the transient, endothelial cell-specific induction of E
      selection by tumor necrosis factor-alpha (TNF-alpha). Subconfluent primary
      cultures, consisting of a mixture of endothelial cells, fibroblasts, and
      keratinocytes, were treated with TNF-alpha for 6 h, and HDMEC were isolated by
      their selective binding to magnetic beads coupled with anti-E-selection
      monoclonal antibody. After two immunomagnetic purification steps, a homogenous
      population of HDMEC was obtained which showed typical cobblestone morphology,
      expressed CD31 and von Willebrand factor, proliferated in response to vascular
      endothelial growth factor, upregulated the expression of intercellular adhesion
      molecule-1 and vascular adhesion molecule-1 in response to TNF-alpha, and formed
      capillary-like tubes in a three-dimensional collagen type I matrix. This simple
      technique may facilitate a more widespread use of microvascular endothelial cell
      cultures obtained from different human or animal organs for functional in vitro
      studies.

PMID- 9570916
TI  - Differentiation responses of embryonic endothelium to leukemia inhibitory factor.
AB  - The IEM cell line is a murine embryonic endothelial cell line that responds to
      combinations of basic fibroblast growth factor (bFGF) and leukemia inhibitory
      factor (LIF) by undergoing proliferation and vasculogenic differentiation in
      vitro and in vivo. Exposure to LIF and bFGF in vitro permits the IEM cells to
      specifically chimerize endothelium in vivo and recapitulate normal endothelial
      development after blastocyst injection. We report here that unmanipulated IEM
      cells form vascular neoplasias when injected into immunodeficient nude mice.
      Examination of IEM neoplasia following exposure in vitro to bFGF and LIF before
      injection into nude mice profoundly reduced or completely suppressed the
      neoplastic growth of IEM cells. Furthermore, this suppression was observed by
      treatment with LIF alone, while bFGF treatment did not significantly alter IEM
      neoplasia and did not modify the LIF-mediated suppression. Characterization of
      the IEM responses to LIF revealed that the LIF suppression of IEM neoplasia
      depended on how long the cells were exposed to LIF in vitro. The IEM cell
      response to LIF was associated with the specific activation of the transcription
      factor Stat3. Stat1 activation could not be detected in response to LIF, although
      it is expressed in IEM cells. Our results demonstrate that the LIF-induced
      differentiation of IEM cells involves suppression of IEM-derived neoplasia and is
      associated with the specific activation of Stat3.

PMID- 9570917
TI  - Stage-specific expression and cellular localization of the heat shock factor 2
      isoforms in the rat seminiferous epithelium.
AB  - Heat shock transcription factors (HSFs) are generally known as regulators of
      cellular stress response. The mammalian HSF1 functions as a classical stress
      factor, whereas HSF2 is active during certain developmental processes, including
      embryogenesis and spermatogenesis. In the present study, we examined HSF2
      expression at specific stages of the rat seminiferous epithelial cycle. We found
      that expression of the alternatively spliced HSF2-alpha and HSF2-beta isoforms is
      developmentally regulated in a stage-specific manner. Studies on cellular
      localization demonstrated that HSF2 is present in the nuclei of early pachytene
      spermatocytes at stages I-IV and in the nuclei of round spermatids at stages V
      VIIab. In contrast a strong HSF2 immunoreactivity was detected in small distinct
      cytoplasmic regions from zygotene spermatocytes to maturation phase spermatids.
      Immunoelectron microscopic analysis revealed that these structures are mainly
      cytoplasmic bridges between germ cells. Our results on cellular localization of
      HSF2 and stage-specific expression of the HSF2 isoforms indicate that HSF2, in
      addition to its function as a nuclear transcription factor, may be involved in
      other cellular processes during spermatogenesis, possibly in the sharing process
      of gene products between the germ cells.

PMID- 9570918
TI  - Multiple intracellular pathways interfere with the activation of a CPP32-like
      protease induced by serum deprivation of AKR-2B cells.
AB  - As previously described, confluent AKR-2B fibroblasts rapidly disintegrate upon
      removal of serum. Platelet-derived growth factor isoforms AB or BB (PDGF-AB, -BB)
      added immediately after serum deprivation caused complete survival of the cells
      without initiating proliferation (Simm et al., 1994, J. Cell. Physiol. 160, 295).
      Here the role of cAMP as a protective agent was investigated by using forskolin
      or 8-Br-cAMP. Both reagents afforded high cellular protection. The phorbolester
      TPA, an activator of protein kinase C isoforms, also exerted a high protection
      against cell death (ED50 = 7 nM). Unexpectedly colchicine (ED50 = 1.5 microM) an
      inhibitor of tubulin polymerization also protected cells from death. The
      protective effects of PDGF-BB and TPA were dependent on protein synthesis as
      indicated by their complete suppression by cycloheximide (CHx). Surprisingly,
      forskolin and 8-Br-cAMP remained effective even in the presence of CHx. Detailed
      studies of several signalling pathways were performed. These investigations
      showed no interference between PDGF-BB and cAMP-dependent pathways at the early
      stage of signal transduction. As previously described, the ICE-like protease
      inhibitor tyr-val-ala-asp-chloromethylketone (YVAD-cmk) protected cells from
      death (Simm et al., 1997, J. Cell Sci. 110, 819-828). As shown here, a
      substantial protection was also achieved by the addition of two other caspase
      inhibitors: asp-glu-val-asp-aldehyde (DEVD-cho; ED50 = 100 microM) and
      benzoylcarbonyl-asp-glu-val-asp-chloromethylketone (Z-DEVD-cmk; ED50 = 100
      microM). The activity of caspases was studied using either tyr-val-ala-asp
      aminomethylcoumarine (YVAD-amc) or asp-glu-val-asp-aminomethylcoumarine (DEVD
      amc) as substrates. There was no activation of a YVADase, whereas as pronounced
      increase in DEVDase activity was found with a maximum 3 h after serum removal.
      Cross competition experiments in vitro showed that the latter activity is
      inhibited also by low concentrations of YVAD-cmk (300-600 nM), suggesting that
      both inhibitors inactivated the same target protease. Remarkably all tested
      protective reagents lead to an inhibition of the DEVDase activity in intact
      cells. Since these reagents act via distinct intracellular pathways, the
      existence of a regulatory element upstream of the DEVDase is proposed which
      integrates signals from a variety of pathways.

PMID- 9570919
TI  - Impairments in both p70 S6 kinase and extracellular signal-regulated kinase
      signaling pathways contribute to the decline in proliferative capacity of aged
      hepatocytes.
AB  - Treatment of primary cultured hepatocytes from adult (6-month-old) rats with
      epidermal growth factor (EGF) results in a marked elevation in DNA synthesis, a
      response that is markedly attenuated in cells of aged (24-month-old) animals.
      Recently we demonstrated that this age-related attenuation is associated with
      reduced activation of extracellular signal-regulated kinase (ERK) in response to
      EGF treatment. In order to gain further insight into the mechanisms responsible
      for the age-related decline in this proliferative response, we investigated the
      expression and/or activities of several other regulatory molecules important for
      G1 to S phase progression in EGF-stimulated young and aged hepatocytes. Induction
      of cyclin D1 and activation of cyclin-dependent kinase 2 (CDK2) by EGF were found
      to be diminished in the aged cells. In young cells, prior treatment with
      rapamycin inhibited the induction of DNA synthesis and activation of CDK2 to
      levels similar to those seen in aged cells without inhibiting ERK activity and
      cyclin D1 expression. This suggested that a distinct, ERK-independent, rapamycin
      sensitive pathway might also contribute to the proliferative response in
      hepatocytes and be subject to age-related alterations. Further studies
      demonstrated that activation of p70 S6 kinase (p70S6k), a rapamycin-sensitive
      event, following EGF treatment was 40% lower in aged hepatocytes relative to
      young cells, although the kinetics of activation did not differ in the two age
      groups. Western blot analysis for p70S6k expression revealed similar levels of
      proteins in young and aged cells. From these findings, we conclude that
      deficiencies in both the ERK and p70S6k signaling pathways contribute to the age
      related decline in the proliferative response of hepatocytes.

PMID- 9570921
TI  - Chondrogenesis in a cell-polymer-bioreactor system.
AB  - Chondrogenesis was studied under controlled in vitro conditions using a cell
      polymer-bioreactor system. Bovine calf articular chondrocytes were seeded onto
      biodegradable polymer scaffolds and cultured in rotating bioreactor vessels.
      Concomitant increases in the amounts of glycosaminoglycan (GAG) and type II
      collagen resulted in cell-polymer constructs with continuous cartilaginous matrix
      over their entire cross sections (6.7 mm diameter x 5 mm thick) after 40 days of
      cultivation. As compared to natural calf cartilage, constructs had comparable
      cellularities, 68% as much GAG and 33% as much type II collagen per gram wet
      weight. The progression of chondrogenesis in chondrocyte-polymer constructs was
      similar to that suggested previously for precursor cells in vitro and developing
      limbs in vivo. In particular, the polymer scaffold provided a three-dimensional
      structure that could be seeded with chondrocytes at high cell densities in order
      to establish cell-to-cell contacts and initiate cartilage tissue development,
      whereas the bioreactor vessel provided a permissive microenvironment for
      chondrogenesis. This work demonstrates the promise of using tissue engineered
      constructs for in vitro studies of cell interactions and differentiation.

PMID- 9570920
TI  - A semiautomated fluorescence-based cell-to-cell fusion assay for gp120-gp41 and
      CD4 expressing cells.
AB  - A novel fluorescence-based method was developed to measure HIV envelope
      glycoprotein (env)-CD4-mediated cell fusion. This method measures the spread of a
      fluorescent dye as the cytosolic compartments of adjacent cells become contiguous
      upon cell-to-cell fusion. Calcein-labeled CD4+ Sup-T1 cells were seeded onto a
      monolayer of unlabeled TF228.1.16 cells, which stably express env, the gp120-gp41
      complex. Changes in the following parameters were measured using a stage-scanning
      laser microscope: total fluorescent area, average fluorescent area, and average
      shape factor. Anti-CD4 monoclonal antibodies, anti-Leu3a, and OKT4E were shown to
      block fusion in a dose-dependent manner, while OKT4 had no effect. Aurin
      tricarboxylic acid, a compound that interferes with the binding of anti-Leu3a mAb
      and gp120 to CD4+ human peripheral blood lymphocytes, T20, a peptide that
      interferes with gp41, and cytochalasin D, a microfilament disrupter, all blocked
      fusion in a dose-dependent manner. This semiautomated assay can be used to
      quickly assess the effectiveness of compounds acting at different sites to block
      CD4 and env initiated cell-to-cell fusion.

PMID- 9570922
TI  - Cloning and identification of genes that associate with mammalian replicative
      senescence.
AB  - Cellular senescence and limited proliferative capacity of normal diploid cells
      has a dominant phenotype over immortality of cancerous cells, suggesting its
      regulation by the expression of a set of genes. In order to isolate the genes
      that associate with senescence, we have employed a clonal system of conditional
      SV40 T antigen rat embryo fibroblast cell lines which undergo senescence upon T
      antigen inactivation. Construction of cDNA libraries from two conditional cell
      lines and application of differential screening and subtractive hybridization
      techniques have resulted in the cloning of eight senescence-induced genes (SGP
      2/Apo J, alpha 1-procollagen, osteonectin, fibronectin, SM22, cytochrome C
      oxidase, GTP-alpha, and a novel gene) and a senescence-repressed gene (FRS-2).
      Three of these genes encode for extracellular matrix proteins, others are
      involved in the calcium-dependent signal transduction pathways, while the SGP
      2/Apo J gene may have a cellular protective function. RNA analysis has shown that
      the senescence-associated genes are overexpressed in both normal rat embryonic
      fibroblasts and human osteoblasts cell cultures undergoing aging in vitro. In
      comparison, the expression of these genes in a rat fibroblast immortalized cell
      line (208F cells) was down-regulated after both its partial and its full
      transformation by ras oncogenes. Thus, cloning of senescence-associated genes
      opens up new ways to elucidate and/or to modulate aging and cancer.

PMID- 9570923
TI  - The fate of thymocytes labeled in vivo with CFSE.
AB  - The fate of thymic emigrants had so far been studied using a variety of markers,
      each of which had inherent limitations as to stability, toxicity, or selectivity.
      We describe a new technique which relies on the in vivo injection of CFSE, an
      esterified vital dye hitherto used at 80 times lower concentrations for in vitro
      cell labeling. We show that CFSE labels a representative sample of all thymocyte
      subsets and that these migrate at a rate of approximately 2-3 x 10(6) cells/day
      to peripheral lymphoid organs. We show that they enter lymph nodes at day 1
      postinjection and stay for at least 21 days, whereas the turnover in the spleen
      is more rapid. We also show by immunohistochemistry, using peroxidase-labeled
      anti-FITC antibodies, that CFSE-labeled thymic emigrants are confined to T
      dependent areas of peripheral lymphoid organs.

PMID- 9570924
TI  - Interaction of integrin alpha 7 beta 1 in C2C12 myotubes and in solution with
      laminin.
AB  - The dimer of integrin alpha 7 and beta 1 is a major laminin-binding receptor in
      skeletal muscle. We studied interactions of integrin alpha 7 beta 1 with the
      extracellular matrix protein laminin in solution and in intact cells. Integrin
      alpha 7 beta 1 bound to EHS laminin (laminin-1, composed of alpha 1, beta 1, and
      gamma 1 chains), but not to endogenous laminin expressed in C2C12 myotubes.
      Northern blot analysis demonstrated that C2C12 myotubes synthesized laminin-1
      alpha, beta, and gamma subunits mRNAs. C2C12 laminin was, however,
      immunologically distinct from EHS laminin; it was not recognized by 5D3 anti
      laminin-1 monoclonal antibody, whereas 5A2 and LT3 antibodies reacted equally
      well with C2C12 and EHS laminins. Following deglycosylation of EHS laminin,
      separation of the subunits by SDS-PAGE, Western blotting, and partial amino acid
      sequencing of the protein bands, the epitope recognized by 5D3 antibody was
      localized to the gamma 1 laminin chain. Following binding in vitro, the complex
      of EHS laminin and integrin alpha 7 beta 1 was subject to chemical cross-linking.
      The two proteins did not undergo cross-linking at the cell surface, consistent
      with the fact that in intact, resting myotubes integrin alpha 7 beta 1 interacted
      poorly with EHS laminin, which may reflect a limited accessibility of integrin
      alpha 7 beta 1 in the membrane to laminin or an inactive state of the integrin.

PMID- 9570925
TI  - Inhibition of chondrogenesis by integrin antibody in vitro.
AB  - Integrins mediate cell attachment to a variety of extracellular matrix proteins.
      These interactions play an important role in morphogenesis and differentiation.
      The mediating functions of integrins during chondrogenesis in vitro were
      investigated by using mesenchymal cells from limb buds of day 12 mouse embryos.
      The cells were treated with anti-beta 1, -alpha 1, and -alpha 5 integrin
      antibodies (a) from day 1 to day 3 and (b) from day 3 to day 7 of cultivation.
      The total culture period was 7 days. The presence of exogenous anti-beta 1, but
      not -alpha 1 and -alpha 5 integrin antibodies, from day 1 to 3 completely
      inhibited the differentiation of blastemal cells to chondroblasts and the
      formation of cartilage matrix. On the other hand, the presence of exogenous anti
      beta 1, -alpha 1, and -alpha 5 integrin antibodies from day 3 of cultivation
      onwards had no effect. Immunoblotting and immunomorphological findings in the
      cultures treated with anti-beta 1 antibody from day 1 to day 3 revealed a pattern
      of integrins and collagen composed of beta 1, alpha 1, alpha 5 beta 1 integrins
      and collagen type I. The cartilage-specific chondroitin sulfate proteoglycan
      (CSPG) could not be demonstrated in these cultures. The cultures treated later
      (day 3 to day 7) showed a pattern of beta 1, alpha 3, alpha 5 beta 1, and alpha v
      beta 3 integrins, collagen types I and II, and CSPG identical to that of the
      untreated controls. These findings indicate that beta 1-integrins play a crucial
      role in early cartilage differentiation and point to a possible important cell
      matrix interaction in the induction of chondrogenesis.

PMID- 9570926
TI  - Bcl-xL modulates apoptosis induced by anticancer drugs and delays DEVDase and DNA
      fragmentation-promoting activities.
AB  - Using an episomal eucaryotic expression vector, we derived three stable
      transfected human leukemic U-937 variant lines showing differential expression of
      the Bcl-xL protein. Preventive effect of Bcl-xL on cell death induced by various
      concentrations of camptothecin (DNA topoisomerase I inhibitor; CPT) was observed
      in the three lines with most pronounced effect in cells containing the highest
      level of Bcl-xL expression. These results show that increased cell death
      protection by Bcl-xL is correlated with its level of expression. The extent of
      DNA strand break formation and DNA synthesis inhibition following CPT treatments
      was similar in control and transfected U-937 cells, suggesting that Bcl-xL acts
      downstream of CPT-DNA topoisomerase I-mediated DNA strand breaks. Modulation of
      cell death by Bcl-xL was also observed in cells treated with etoposide,
      vinblastine, paclitaxel, and cisplatinum (II) diammine dichloride. To define
      whether Bcl-xL functions downstream or upstream of apoptogenic proteolytic
      cascade activation, we compared kinetics of DNA fragmentation in treated cells
      with kinetics of caspase 1-like, caspase 3-like, and N-tosyl-L
      phenylalanylchloromethyl ketone (TPCK)-sensitive activities. In CPT-treated U-937
      cells, caspase 3-like and TPCK-sensitive activities promoting DNA fragmentation
      in a cell-free system were detected much more rapidly in extracts obtained from
      CPT-treated U-937 cells compared to those obtained from CPT-treated U-937-Bcl-xL
      variant cells. These results suggest that Bcl-xL delays their activation that
      correlates with the occurrence of DNA fragmentation. Addition of recombinant Bcl
      xL in extracts containing DEVDase and TPCK-sensitive activities did not inhibit
      these activities, suggesting that Bcl-xL acts primarily upstream of their
      activation in the apoptotic process. Taken together, these results suggest that
      Bcl-xL is a primary checkpoint that can block or delay transmission of cell death
      signals emerging from DNA damage and prevents activation of an apoptogenic
      proteolytic cascade.

PMID- 9570927
TI  - Stimulation of rat liver mitochondrial fusion by an outer membrane-derived
      aluminum fluoride-sensitive protein fraction.
AB  - In normal livers, hepatocytes contain a large number of spheroidal mitochondria.
      Mitochondrial morphology changes drastically in liver disease, but the underlying
      fusion-fission mechanisms are not known. We detected GTP- and aluminum fluoride
      dependent membrane fusion events between rat liver mitochondria. Separation of
      outer mitochondrial membrane-derived proteins led to a subfraction containing a
      60-kDa protein band that is detected by specific antibodies directed to common
      amino acid sequences of the GTP-binding site or carboxyl-terminus of eukaryotic
      heterotrimeric G-protein alpha subunits. Addition of this subfraction and
      aluminum fluoride to permeabilized rat hepatocytes triggered a substantial
      morphological change in hepatic mitochondria, giving them the three-dimensional
      appearance of a tubulovesicular network. Comparative stereology using electron
      and confocal microscopy showed that these morphological changes represent true
      mitochondrial fusion. Addition of aluminum fluoride alone induces a more limited
      change in mitochondrial morphology, from spheroidal organelles to short rods.
      Mitochondria maintained their normal membrane potential and overall membrane
      ultrastructure after all these morphological changes. Our results reveal that
      mammalian liver mitochondria contain proteins that stimulate mitochondrial fusion
      and suggest that members of the GTPase superfamily control the normalcy of
      mitochondrial morphology, which is closely linked to physiological cellular
      energetics.

PMID- 9570929
TI  - Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal
      transduction in B lymphoma cells.
AB  - Crosslinking of major histocompatibility complex class I (MHC-I) molecules on the
      surface of human B lymphoma cells was shown to induce protein tyrosine
      phosphorylation and mobilization of intracellular free calcium.
      Immunoprecipitations indicated that the protein tyrosine kinases p53/56lyn and
      p72syk are among the tyrosine-phosphorylated proteins. The kinetics of
      phosphorylation of these kinases after MHC-I crosslinking differ from the
      kinetics observed after crosslinking of the B cell antigen receptor (BCR).
      Additional experiments were performed with chicken lyn- and syk-negative DT40 B
      cells and the results indicate that these two kinases have different substrate
      specificity and regulate intracellular free calcium differently in response to
      MHC-I crosslinking. In addition MHC-I crosslinking of a sIgM-negative DT40
      chicken B cell variant results in less activity of tyrosine kinases and less
      mobilization of intracellular free calcium compared with MHC-I crosslinking of
      wild-type DT40 cells. Thus, expression of BCR at the cell surface is likely to be
      important for the signal cascade initiated by MHC-I crosslinking. Our data
      suggest that signal transduction initiated through ligation of the MHC-I molecule
      plays a role in the regulation of B cell homeostasis.

PMID- 9570930
TI  - Relationships between corticosterone concentration and season, time of day and
      confinement in a wild reptile (tuatara, Sphenodon punctatus).
AB  - Seasonal and daily variation in basal plasma concentrations of corticosterone and
      the effect of short-term confinement on plasma corticosterone concentration were
      examined in wild adult male and female tuatara (Sphenodon punctatus) on Stephens
      Island, New Zealand. Males and females sampled immediately upon capture at night
      (active period) showed significant variation in basal plasma corticosterone among
      four seasons of the year, and females also showed variation in concentration
      between reproductive states sampled at the same time. Highest basal
      concentrations in females were seen in November, when the level in gravid females
      about to nest (4.45 +/- 0.66 ng/ml; mean +/- SE) was almost twice that in
      nonnesting females at the same time (2.48 +/- 0.30 ng/ml). Plasma samples
      collected from tuatara at dusk, middle of the night, dawn, and middle of the day
      showed no significant daily variation in corticosterone concentration in either
      summer or winter. In these samples, significant positive correlations between
      body temperature and log plasma corticosterone were observed in males in summer
      and winter, but not in females in either season. Mean corticosterone
      concentrations in tuatara held in cloth bags for 3 h were significantly higher
      than in free-roaming controls (P < 0.01), with mean concentrations in males about
      23 times, and vitellogenic females 9 times, those of their respective controls.
      Plasma corticosterone concentrations measured in this stress study were compared
      with previously published concentrations for plasma sex steroids in the same
      individuals. Corticosterone was positively correlated with progesterone (both
      sexes), but not with testosterone (both sexes) or estradiol (measured in females
      only). In summary, wild adult tuatara have low basal levels of plasma
      corticosterone that vary seasonally, but not diurnally. As in other reptiles,
      corticosterone concentration shows a significant elevation in response to short
      term confinement.

PMID- 9570928
TI  - Tyrosine kinase cell signaling pathways of rat mesangial cells in 3-dimensional
      cultures: response to fetal bovine serum and platelet-derived growth factor-BB.
AB  - Cells grown in 3-dimensional collagen gels adopt a nonproliferative, contractile
      phenotype which is more characteristic of cells in vivo than cells grown in 2
      dimensional culture. The floating collagen gel contraction assay is a well
      defined system used to study cell-extracellular matrix interactions grown in 3
      dimensional culture. Although the cell biology of this system is well defined,
      the cell signaling associated with gel contraction has not been well
      characterized. In this study we demonstrate that fetal bovine (FBS) and platelet
      derived growth factor (PDGF)-induced mesangial cell-collagen gel contraction is
      associated with increased tyrosine phosphorylation of a number of proteins
      including focal adhesion kinase (FAK) and the 42-kDa isoform of MAPK (ERK2). FBS
      induced gel contraction is not affected by the presence of the MEK inhibitor
      PD098059. Low concentrations of PDGF-BB (10 ng/ml) induce gel contraction;
      however, at higher PDGF-BB concentrations (80 ng/ml) gel contraction is not
      observed. PDGF-BB-induced gel contraction as well as tyrosine phosphorylation of
      FAK are inhibited in the presence of the PI-3 kinase inhibitor wortmanin. Minimal
      autophosphorylation of the PDGF-beta receptor is observed under 3-dimensional
      culture conditions following PDGF-BB stimulation; however, when mesangial cells
      grown in 2-dimensional culture are exposed to PDGF-BB, the PDGF-beta receptor was
      prominently phosphorylated. We conclude that induction of collagen gel
      contraction by FBS and PDGF-BB is associated with tyrosine kinase phosphorylation
      and that these responses differ substantially from what occurs in 2-dimensional
      cultures in the presence of the same agonists.

PMID- 9570931
TI  - Cloning of cDNA encoding the common alpha subunit precursor molecule of pituitary
      glycoprotein hormones in the Australian lungfish, Neoceratodus forsteri.
AB  - We have isolated cDNA clones encoding a putative glycoprotein hormone alpha
      subunit precursor molecule from a pituitary cDNA library of the Australian
      lungfish (Neoceratodus forsteri) by a two-step plaque hybridization technique
      initially using cDNA encoding the toad glycoprotein hormone alpha subunit
      precursor molecule as the hybridization probe. The inserts (799 bp) of two of the
      isolated cDNA clones contained sequences of 5' and 3' untranslated regions,
      including a poly(A) stretch, and the entire coding sequence of the alpha subunit
      precursor molecule. The deduced amino acid sequence showed that its signal
      peptide consists of 24 residues and its mature protein 97 residues. In the mature
      protein, there is an insert of one residue (Ala) just after the 9th residue. This
      insert is unique to the Australian lungfish among vertebrate species studied. The
      amino acid sequence of the mature protein shares the common, or the same-group,
      amino acid residues at 9 positions with tetrapod and not actinopterygian
      vertebrates, while only one residue is common to some teleosts and the lungfish
      to the exclusion of the tetrapods. The overall sequence of the mature protein of
      the Australian lungfish also shares more similarity with those of tetrapods (69
      to 84%) than it does with teleosts (57 to 74%). These results on the relation of
      the alpha subunit precursor molecule between the lungfish and other vertebrates
      are consistent with the recent molecular phylogenetic studies suggesting a closer
      relationship between lungfish and tetrapods than between lungfish and teleosts.
      We also found that the primary structure of the lungfish alpha subunit is
      slightly but significantly more similar to that of homeothermic vertebrates than
      to that of amphibians. This may be due to specialization of the amphibian alpha
      subunit molecules.

PMID- 9570932
TI  - Comparative binding affinity study of progestins to the cytosol progestin
      receptor of endometrium in different mammals.
AB  - The relative binding affinity of 5 alpha-reduced progestins and a newly
      synthesized antiprogestin J912 (progesterone 100%) was determined in a
      competitive receptor binding assay using [3H]ORG-2058 as radiolabeled ligand for
      the progestin receptor. Uteri obtained from 12 different species of four
      mammalian orders were examined. The relative binding affinity of 75-100% and a
      blood prevalence of 5 alpha-pregnane-3,20-dione in horses and African elephants
      suggest a biological role of this particular 5 alpha-reduced progesterone. For
      pigs the binding affinity of 5 alpha-pregnane-3,20-dione was about 50% of
      progesterone, but blood levels are unknown. In all other cases the low binding
      affinity of investigated progestins precludes possible biological role. For 5
      alpha-pregnane-3 alpha-ol-20-one, 5 alpha-pregnane-20 alpha-ol-3-one, and 5 alpha
      pregnane-3 beta,20 alpha-diol the relative binding affinity was less than 1%. A
      rather low binding (< 15%) was observed in 5 alpha-pregnane-3,20-dione in all
      ruminant species investigated. The antiprogestin J912 was found to be highly
      efficient in displacing progesterone from its endometrial binding sites in
      carnivores and might therefore be used for pregnancy interruption during diapause
      in certain species, e.g., in captive bears.

PMID- 9570933
TI  - Immunohistochemical studies of the endocrine cells within the gastro-entero
      pancreatic system of Osteoglossomorpha, an ancient teleostean group.
AB  - The identification and distribution of endocrine cells within the gastro-entero
      pancreatic (GEP) system of five species of the Osteoglossomorpha (Osteoglossum
      bicirrhosum, Scleropages jardini, Pantodon buchholzi, Notopterus chitala and
      Gnathonemus petersii) were analyzed by immunohistochemistry. Four immunoreactive
      cell types were identified within the pancreatic islets (A, B, D, and F cells),
      using antisera directed against mammalian insulin (m-INS), somatostatins (SST-14,
      SST-25), and members of the pancreatic polypeptide (aPY, NPY, PYY) and glucagon
      (GLU, GLP) families. The B cells were located throughout the center of the islets
      in the five species and, in general, D cells had a similar distribution. However,
      immunoreactivity to anti-somatostatins varied between four of the species and G.
      petersii, which showed less intensely stained D cells in the islets, but greater
      SST immunoreactivity in both the intestinal and the stomach epithelia than in
      comparable epithelia of other species. For peptides of both the pancreatic
      polypeptide and the glucagon families, the immunoreactivity was detected at the
      periphery of the islets, and there was a suggestion of an interfamily
      colocalization of peptides in some cells. In addition, glucagon family peptides
      showed a scattered immunoreactivity throughout the central portion of the islets.
      A moderately abundant number of cells in the intestine were immunoreactive to the
      PP family antisera in all five species. However, immunoreactivities to GLU, GLP,
      SST, and m-INS antisera were variable in intestinal cells of the species.
      Immunoreactivity with sera raised against m-INS and PYY was also observed in the
      stomach of P. buchholzi. The significance of these findings is discussed in both
      ontogenetic and phylogenetic contexts with respect to the GEP system in
      actinopterygian fishes and with respect to the possibility of variable processing
      of prohormones in the different organs of these osteoglossomorphs.

PMID- 9570934
TI  - Tetrapod-type [Asp1] angiotensin is present in a holostean fish, Amia calva.
AB  - The renin-angiotensin system has been identified in various vertebrates, from
      elasmobranchs to mammals. Tetrapod (amphibians to mammals) angiotensin (ANG) has
      Asp at the N-terminus, but Asp is replaced by Asn in elasmobranch and teleost
      fish. ANG I has been isolated from incubates of plasma and kidney extracts of the
      bowfin Amia calva, a holostean fish, using the eel vasopressor activity as an
      assay system; its sequence was found to be H-Asp-Arg-Val-Tyr-Val-His-Pro-Phe-Asn
      Leu-OH after sequence analysis, mass spectrometry, and comparison with the
      synthetic peptide. This sequence is identical to bullfrog ANG I. [Asn1] ANG I was
      not detected. Thus the bowfin is the first fish species which contains only
      [Asp1] ANG I. The bowfin ANG I and II were no more vasopressor than eel peptides
      in the bowfin, indicating that bowfin ANG II receptors do not distinguish between
      [Asp1] and [Asn1] peptides. In the rat, bowfin ANG I and rat [Ile5, His9] ANG I
      have equipressor activities when examined in different animals, but the
      vasopressor activity of bowfin ANG I decreased following rat ANG I in the same
      animals, although the activity of rat ANG I was unaffected after bowfin ANG I.
      The present study directly demonstrates the presence of the renin-angiotensin
      system in a holostean fish and showed that its ANG II receptors have not yet
      fully coevolved with the homologous [Asp1] peptide.

PMID- 9570935
TI  - Insulin during the early postembryonic development of the gilt-head sea bream,
      Sparus aurata: ultrastructural, immunohistochemical, and biochemical studies.
AB  - Insulin was sought during the early postembryonic development of gilt-head sea
      bream, Sparus aurata, using ultrastructural, immunohistochemical and biochemical
      techniques. The endocrine pancreas appeared at hatching (Day 0) as a single
      cluster of morphologically similar cells. Secretory granules formed from Day 1
      onwards but the cells could only be identified as insulin-producing B cells at
      the end of the endotrophic period (Day 3-Day 4). Insulin-immunoreactive cells
      were detected in the pancreatic primordium from hatching onwards and their number
      increased after the end of the endo-exotrophic period. Early insulin production
      was also found using an ELISA method on homogenates of prelarvae and larvae.
      Insulin levels were fairly high during the endotrophic period, decreased strongly
      at mouth opening, and then increased at the end of the endo-exocrine period. The
      origin and role of the large amount of hormone detected during the strictly
      endotrophic phase of ontogenesis are discussed in light of data on other
      vertebrates.

PMID- 9570936
TI  - Neuropeptide Y-like gene expression in the salmon brain increases with fasting.
AB  - In mammals there is a well-established connection between neuropeptide Y (NPY)
      and the balance between energy intake and expenditure: NPY stimulates food intake
      and the hypothalamus shows a dramatic increase in NPY mRNA in response to
      fasting. The widespread occurrence of NPY in the brains of all vertebrates
      investigated raises the possibility that NPY may be involved in food intake and
      energy balance regulation in nonmammalian vertebrates as well. We used in situ
      hybridization to examine whether brain NPY-like gene expression is involved in
      energy balance regulation in salmon. A radiolabeled oligonucleotide probe was
      employed to screen the salmon forebrain and parts of the midbrain for NPY-like
      mRNA. Distribution of NPY-like gene expression was determined, followed by
      examination of brains from fed or food-deprived chinook and coho salmon. Regions
      expressing NPY-like mRNA were the caudoventral telencephalon, preoptic area,
      thalamus, optic tectum, and caudal hypothalamus. The region showing a difference
      in NPY-like gene expression between fed and fasted individuals was the preoptic
      area of the hypothalamus where significantly greater hybridization signal area
      was found with fasting. Plasma insulin levels were also shown to differ, with
      fasted animals having significantly lower insulin levels. These results suggest
      that the role of NPY-like peptides in the regulation of energy balance may have
      arisen early in vertebrate evolution.

PMID- 9570937
TI  - Localization and changes in distribution of brain alpha 2- and beta-adrenoceptors
      in response to acclimation state in the American bullfrog (Rana catesbeiana).
AB  - Alpha (alpha)- and beta (beta)-adrenoceptors regulate physiological processes in
      vertebrates. This study determined the location of alpha 2- and beta
      adrenoceptors in the brain of the American bullfrog, Rana catesbeiana, using
      autoradiography. As the density of receptors may be affected by environmental
      temperature, a comparative numerical analysis of adrenoceptors in the areas of
      localization with respect to warm and cold acclimation was also carried out.
      Areas of greatest concentration of alpha 2-adrenoceptors were the accessory
      olfactory bulb, medial pallium, and olfactory bulb. Adrenoceptor numbers were
      significantly decreased in the accessory olfactory bulb and medial pallium in
      cold-acclimated animals. beta-adrenoceptors were localized in the thalamus,
      cerebellum, medial pallium, and amygdala/ striatum. Cold acclimation decreased
      adrenoceptor density in medial pallium and torus semicircularis and increased
      adrenoceptor density in the thalamus and hypothalamic preoptic areas. Among the
      alpha 2- and beta-adrenoceptors, only four regions of overlap existed, the medial
      pallium, hypothalamic preoptic area, optic tract, and isthmic tegmentum.
      Otherwise, where there were alpha 2-adrenoceptors, there were few or no beta
      adrenoceptors. No alpha 2- or beta-adrenoceptors were found in the pituitary and
      optic chiasm. The distribution of adrenoceptors in particular areas of the brain
      may have functional significance with respect to physiological changes which
      occur in response to hibernation.

PMID- 9570938
TI  - An immunohistochemical study of temperature-related changes in galanin and nitric
      oxide synthase immunoreactivity in the hypothalamus of the toad.
AB  - Galanin (GAL) and nitric oxide synthase (NOS) have been implicated in the control
      of thermogenesis in mammals. An experimental protocol was designed to determine
      whether or not the expression of these molecules in the hypothalamus of the toad
      could be related to environmental temperature changes. Exposure of the animals to
      low temperature increased the number and intensity of NOS-positive neurons in the
      magnocellular hypothalamic region, in contrast to a weak immunoreactivity
      observed in control animals kept in a natural environment at a spring-summer
      temperature (23-27 degrees C). Also a significantly higher number of GAL
      immunoreactive (-IR) cells was observed in the preoptic area as compared to that
      observed in controls, while no difference in the intensity of GAL immunostaining
      intensity was detected. These results show a temperature-related expression of
      GAL and NOS in the hypothalamus and preoptic area of the toad. The results
      suggest a possible role of GAL and NOS in the regulation of hibernation in these
      animals.

PMID- 9570939
TI  - An immunohistochemical and morphometric analysis of insulin, insulin-like growth
      factor I, glucagon, somatostatin, and PP in the development of the gastro-entero
      pancreatic system of Xenopus laevis.
AB  - The ontogeny of the classical islet hormones insulin (INS), glucagon (GLUC),
      somatostatin (SOM), and pancreatic polypeptide (PP) as well as insulin-like
      growth factor I (IGF-I) in the gastro-entero-pancreatic (GEP) system of Xenopus
      laevis (stages 41-66) was studied using double immunofluorescence and
      morphometric analysis. As early as stage 41, clustered INS-immunoreactive (-IR)
      and isolated GLUC-IR cells occurred in the pancreas. The first SOM-IR cells
      appeared at stage 43, followed by PP-IR cells at stage 46. About 79% of the PP
      immunoreactivity was confined to a subpopulation of the GLUC-IR cells. Both the
      GLUC/PP-IR cells and the PP-IR cells were located in a distinct area of the
      pancreas. The first islets occurred in premetamorphosis (around stage 50) and
      comprised mainly INS-IR and GLUC-IR cells. The majority of SOM-IR, PP-IR, and
      GLUC/PP-IR cells was dispersed. The numbers of hormone cells remained quite
      constant until the end of prometamorphosis (stage 58). Around stages 60-62, the
      islets were partly disintegrated and the numbers of islet cells slightly
      decreased. At stage 63, the cell number began to increase and reached the levels
      typical for the adult around stage 66. After metamorphic climax, the islets were
      reformed. In the gastrointestinal tract, transient INS-IR cells occurred prior to
      the adaptation of the gastrointestinal tract to feeding (stages 41-44) and during
      metamorphosis when there is remodeling of the gastrointestinal tract (stages 60
      63). Therefore, INS released from the transient mucosal INS-IR cells may be
      involved in the temporary proliferation of mucosal epithelial cells. The first
      GLUC-IR and SOM-IR cells were seen at stage 41. PP-IR cells followed at stage 46.
      In contrast to the islets, GLUC-IR and PP-IR cells constituted different cell
      populations. Around stage 46, the first IGF-I immunoreactions appeared in the GEP
      system. In pancreas, IGF-I immunoreactivity was found in the GLUC/PP-IR, cells
      (85-99%) but was absent from INS-IR, GLUC-IR, and SOM-IR cells. The IGF-I-IR
      gastro-entero-endocrine cells, however, seemed to contain none of the classical
      islet hormones.

PMID- 9570941
TI  - Rainbow trout glucocorticoid receptor overexpression in Escherichia coli:
      production of antibodies for western blotting and immunohistochemistry.
AB  - Fragments of cDNA that encode the N-terminal and DNA-binding domains (DBD) of the
      rainbow trout glucocorticoid receptor (rtGR) were expressed in Escherichia coli
      as fusion proteins with glutathione-S-transferase (GST). The fusion proteins
      induced by IPTG could readily be detected as 45- and 40-kDa bands, respectively,
      in crude extracts, as well as in proteins purified on glutathione-agarose. These
      purified hybrid proteins were used to immunize rabbits. The antisera produced
      were tested for specificity by Western blot analysis using extracts from COS-1
      cells transfected with an rtGR expression vector and from trout liver cells. The
      antisera raised against the DBD domain did not detect any bands on Western blots,
      even at low antiserum dilution. However, the purified DBD fusion protein
      specifically bound GRE-containing DNA fragments in gel-shift assays, and the
      retarded complexes were supershifted by these antibodies. The antisera raised
      against the N-terminal domain consistently detected two protein bands at 104 and
      100 kDa in the two cell extracts and allowed specific immunohistochemical
      staining in fish brain and pituitary. For the first time in fish, these
      antibodies will allow analysis of GR expression in different cortisol target
      tissues.

PMID- 9570940
TI  - Thyroidectomy of house sparrows (Passer domesticus) prevents photo-induced
      testicular growth but not the increased hypothalamic gonadotrophin-releasing
      hormone.
AB  - Thyroidectomy of starlings (Sturnus vulgaris) prevents the decrease in
      hypothalamic gonadotrophin-releasing hormone (GnRH) which normally occurs at the
      onset of photorefractoriness. To extend this observation to another species,
      changes in testicular mass, bill colour, moult, and hypothalamic GnRH content
      were monitored in photostimulated and nonphotostimulated intact and
      thyroidectomized house sparrows (Passer domesticus). Photostimulated intact birds
      rapidly increased testicular mass and GnRH. Later, testicular mass and GnRH
      decreased, and birds moulted, as they became photorefractory. Nonphotostimulated
      intact birds showed an increase in testicular mass and GnRH. Neither
      photostimulated nor nonphotostimulated thyroidectomized birds showed a marked
      increase in testicular mass, but both showed an increase in GnRH. Photostimulated
      thyroidectomized birds showed no subsequent decrease in GnRH and they did not
      moult. It is suggested that in this species, thyroidectomy inhibits the release
      of GnRH as well as preventing the downregulation of GnRH synthesis normally
      associated with the development of photorefractoriness.

PMID- 9570942
TI  - Spatial and temporal distribution of proopiomelanotropin and proopiocortin mRNA
      during the life cycle of the sea lamprey: a qualitative and quantitative in situ
      hybridization study.
AB  - Two POMC-like pituitary prohormones proopiocortin (POC) and proopiomelanotropin
      (POM) have been characterized from adult sea lampreys (Petromyzon marinus). POC
      encodes a nasohypophysial factor (NHF), ACTH, an MSH, and beta-END; and POM
      encodes MSH-A, MSH-B, and beta-END. Two radiolabeled riboprobes, one encoding a
      unique portion of POC mRNA and the other encoding the MSH-B domain unique to POM
      mRNA, were generated in order to examine the expression of POC and POM during the
      life cycle of the sea lamprey by in situ hybridization. POC expression appears
      evenly distributed throughout most cells of the rostral pars distalis (RPD)
      during the entire life cycle. POC expression also occurs in scattered cells of
      the caudal (proximal) pars distalis (CPD) at stage 5 of metamorphosis. By the
      prespawner period, POC expression is mainly distributed in the dorsal aspect of
      this region. POM expression was completely confined to most cells of the pars
      intermedia (PI) at all periods examined. Quantitative, computer-assisted, image
      analysis of POM expression revealed high signal densities in all larvae which
      decreased by early metamorphosis, steadily increased and reached high levels by
      late metamorphosis (stages 6 and 7), and attained even higher levels in
      prespawners. Volumetric analysis revealed that the net volume of POM expressing
      cells is at its lowest in larvae and increases during subsequent development.
      Analysis of signal density and volumetric measurements of POC expression revealed
      that POC expression in the RPD is low in larvae and steadily increases during
      subsequent intervals of the life cycle reaching very high levels by the
      prespawning period. POC expression in the CPD, first visible at stage 5,
      increases steadily throughout the remainder of metamorphosis and reaches the
      highest levels of expression in prespawning animals. These results would
      implicate the role of POM and POC in some developmental processes but not in the
      initiation of metamorphosis. The very high levels of POM and POC expression in
      prespawner animals suggest that the two genes may have important roles at this
      time in the life cycle of lampreys.

PMID- 9570943
TI  - Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3.
AB  - The gene-rich telomeric region of 21q harbors several loci relevant to human
      diseases including autoimmune polyglandular disease type I, nonsyndromic
      deafness, Knobloch syndrome, holoprosencephaly, and bipolar affective disorder. A
      contig of genomic clones in this region would facilitate the isolation of these
      genes. However, distal 21q22.3 has yet been poorly mapped, presumably due to the
      presence of sequences that are underrepresented in yeast artificial chromosome
      (YAC) libraries. We generated a framework of YACs and used these clones as
      starting points for the isolation of a combination of bacterial artificial
      chromosome clones, P1-derived artificial chromosome clones, and cosmid clones by
      chromosome walking procedures. These studies resulted in the construction of a
      high-resolution contig map spanning the 2.5-Mb region from PFKL to the telomere,
      approximately 2 Mb of which are covered by ready-to-sequence contigs. Within this
      map we determined the location and relative distance of 21 markers. These include
      9 established genetic markers, the order of which is cen-PFKL-D21S154-D21S170
      D21S171-D21S1903- D21S1897- D21S112-D21S1446-D21S1575-tel. Moreover, we
      established the precise map position of 13 genes and 4 ESTs including the
      recently isolated genes C21ORF2, SMT3H1, RNA editing deaminase 1 (ADARB1), folate
      transporter (SLC19A1), COL18A1, lanosterol synthase (LSS-PEN), pericentrin
      (PCNT), and arginine methyltransferase (HRMT1L1). This integrated map provides a
      useful resource for the mapping and isolation of disease genes and for the
      construction of a complete transcription map of distal 21q as well as for large
      scale sequencing efforts.

PMID- 9570944
TI  - Localization of 67 exons on a YAC contig spanning 1.5 Mb around the multidrug
      resistance gene region of human chromosome 7q21.1.
AB  - A contig of 21 nonchimeric yeast artificial chromosomes (YACs) was previously
      assembled across 1.5 Mb of the multidrug resistance (MDR) gene (PGY1 and PGY3)
      region of human chromosome 7q21.1. This region of the human genome has now been
      subjected to exon amplification to detect the presence of additional genes. Exon
      trapping was performed directly on the YACs. Sixty-seven gene fragments were
      isolated and characterized by sequence analysis and comparison with public
      databases. The localization of these exons in the 1.5-Mb region was determined by
      hybridization to YAC clones, and they were localized in 11 subregions of YAC
      contigs. The exon collection includes 21 exons that were identical to known cDNA
      sequences of PGY1, PGY3, sorcin (SRI), the cDNA similar to the delta subunit of
      the human amiloride-sensitive Na- channel (SCNED), and 4 cDNAs with unknown
      function; 43 exons that showed homology/similarity to known cDNA sequences of
      mouse DMP1, rat COT, mouse and human NADHD, human MDC, 3 cDNAs encoding possible
      membrane proteins, and 21 other cDNAs; and 3 exons that shared no
      homology/similarity with any sequence in public databases. The nucleotide
      sequences of all the PGY1 and PGY3 exons were identical to the corresponding cDNA
      sequences previously determined, and these exons were localized to the expected
      positions on the appropriate YAC clones. No other member of the MDR gene family
      thus appeared to be present in the 1.5-Mb region. The integrated physical and
      exon maps should prove valuable for both fine mapping and determination of a
      complete gene map of this segment of the genome.

PMID- 9570945
TI  - Generation of a 3-Mb PAC contig spanning the Miyoshi myopathy/limb-girdle
      muscular dystrophy (MM/LGMD2B) locus on chromosome 2p13.
AB  - Miyoshi myopathy (MM) and limb-girdle muscular dystrophy subtype 2B (LGMD2B) map
      to the same region on chromosome 2p13. To facilitate the cloning of the defective
      gene causing these two diseases, we used a combination of chromosome walking and
      expressed sequence tag (EST) screening and identified 864 P1-derived artificial
      chromosomes (PACs) whose inserts map to the MM/LGMD2B candidate region and
      surrounding areas. Among them, 139 are from a chromosome 2-specific PAC library
      and 725 are from a total genomic PAC library. A 3-Mb contig spanning the
      candidate region for MM/LGMD2B was assembled. This contig contains 200 PACs, 10
      known genetic markers, 5 new polymorphic markers, 57 sequence tagged sites (STSs)
      generated from PAC end fragments, and 4 random STSs. In addition, we mapped 24
      ESTs to this contig and excluded 37 ESTs from the contig, thus eliminating them
      as candidate MM/LGMD2B genes. The high-resolution, sequence-ready PAC contig for
      the MM/LGMD2B region provides a backbone for the identification of the disease
      gene(s) and for clarification of the relationship between the two diseases.

PMID- 9570946
TI  - A methylation imprint mark in the mouse imprinted gene Grf1/Cdc25Mm locus shares
      a common feature with the U2afbp-rs gene: an association with a short tandem
      repeat and a hypermethylated region.
AB  - We identified a sperm-specific methylation imprint mark (Site II) associated with
      a short tandem repeat sequence and a site/region methylated in both gametes (Site
      I) in the Grf1 locus on mouse chromosome 9, which shared a common feature with
      the U2afbp-rs gene. Sites or regions of gamete-specific methylation in imprinted
      genes are strong candidates for carrying information regarding the parental
      origin of alleles. The gamete-specific methylation pattern of Sites I and II was
      conserved after fertilization, but attained the somatic cell pattern by the
      blastocyst stage. In primordial germ cells, Site I was methylated, but Site II
      was unmethylated in both male and female embryos, suggesting that the sperm
      specific methylation imprint mark in Site II was established during
      spermatogenesis. These common features in methylation imprint regions may be a
      clue to identifying regions carrying primary information for the imprinting
      regulation.

PMID- 9570947
TI  - Divergently transcribed overlapping genes expressed in liver and kidney and
      located in the 11p15.5 imprinted domain.
AB  - Human chromosomal band 11p15.5 has been shown to contain genes involved in the
      development of several pediatric and adult tumors and in Beckwith-Wiedemann
      syndrome (BWS). Overlapping P1 artificial chromosome clones from this region have
      been used as templates for genomic sequencing in an effort to identify candidate
      genes for these disorders. PowerBLAST identified several matches with expressed
      sequence tags (ESTs) from fetal brain and liver cDNA libraries. Northern blot
      analysis indicated that two of the genes identified by these ESTs encode
      transcripts of 1-1.5 kb with predominant expression in fetal and adult liver and
      kidney. With RT-PCR and RACE, full-length transcripts were isolated for these two
      genes, with the largest open reading frames encoding putative proteins of 253 and
      424 amino acids. Database comparison of the predicted amino acid sequence of the
      larger transcript indicated homology to integral membrane organic cation
      transporters; hence, we designate this gene ORCTL2 (organic cation transporter
      like 2). An expressed sequence polymorphism provided evidence that the ORCTL2
      gene exhibits "leaky" imprinting in both human fetal kidney and human fetal
      liver. The mouse orthologue (Orctl2) was identified, and a similar polymorphism
      was used to demonstrate maternal-specific expression of this gene in fetal liver
      from interspecific F1 mice. The predicted protein of the smaller gene showed no
      significant similarity in the database. Northern and RACE analyses suggest that
      this gene may have multiple transcription start sites. Determination of the
      genomic structure in humans indicated that the 5'-end of this transcript overlaps
      in divergent orientation with the first two exons of ORCTL2, suggesting a
      possible role for antisense regulation of one gene by the other. We, therefore,
      provisionally name this second transcript ORCTL2S (ORCTL2-antisense). The
      expression patterns of these genes and the imprinted expression of ORCTL2 are
      suggestive of a possible role in the development of Wilms tumor (WT) and
      hepatoblastoma. Although SSCP analysis of 62 WT samples and 10 BWS patients did
      not result in the identification of any mutations in ORCTL2 or ORCTL2S, it will
      be important to examine their expression pattern in tumors and BWS patients,
      since epigenetic alteration at these loci may play a role in the etiology of
      these diseases.

PMID- 9570948
TI  - Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and
      susceptibility to Parkinson disease.
AB  - We analyzed the gene encoding the 24-kDa subunit of mitochondrial complex I,
      which has been implicated in the pathogenesis of Parkinson disease (PD). We set
      out to identify a polymorphism in the 24-kDa subunit gene (NDUFV2) in patients
      with PD and determine whether genetic polymorphism of this gene is associated
      with a higher risk of PD. The subjects comprised 126 patients with PD, and the
      control group comprised 113 unrelated individuals without neurodegenerative
      disorders. A novel polymorphism (Ala29Val) in the mitochondrial targeting
      sequence of NDUFV2 was found in patients with PD. The distribution of the three
      genotypes was significantly different between the two groups (chi 2 = 7.53, df =
      2, P = 0.023). The frequency of homozygotes for the mutation was significantly
      higher in PD patients (23.8%) than in control subjects (11.5%, Fisher's exact
      test, P = 0.0099 < 0.01). The risk of developing PD associated with homozygosity
      for this mutation was calculated as 2.40 (95% CI: 1.18-4.88). NDUFV2 constitutes
      one genetic risk factor for PD, and the mutation may well be a cause of complex I
      deficiency in this disease.

PMID- 9570949
TI  - A new isoform of human myosin phosphatase targeting/regulatory subunit (MYPT2):
      cDNA cloning, tissue expression, and chromosomal mapping.
AB  - Myosin phosphatase target subunit 1 (MYPT1), a subunit of myosin phosphatase,
      plays a pivotal role in the regulation of myosin phosphatase activity. Here we
      have cloned a novel isoform of MYPT1, termed MYPT2, from a human brain cDNA
      library screened with a cDNA fragment of rat MYPT1. Overlapping clones indicated
      an open reading frame of 3763 nucleotides and a predicted polypeptide of mass
      110,398. Ankyrin repeats and leucine zipper motifs were identified for the
      sequences 57-316 and 956-982, respectively. Overall, the deduced amino acid
      sequence of MYPT2 was 61% identical to MYPT1. MYPT2 gene is transcribed
      abundantly in heart and skeletal muscle, while Western blots using an antibody
      specific for MYPT2 showed exclusive expression of MYPT2 in heart and brain. A
      recombinant of the N-terminal two-thirds of MYPT2 bound to the catalytic subunit
      of type 1 phosphatase (delta isoform) and increased activity toward
      phosphorylated myosin light chain. In situ hybridization localized the human
      MYPT2 gene on chromosome 1q32.1, compared to the chromosomal location 12q15-q21-2
      for MYPT1. It is suggested that the products of the two gene families of myosin
      phosphatase target subunit may be localized differently among various tissues.

PMID- 9570950
TI  - Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of
      Drosophila hairy and Enhancer of split.
AB  - Hes2 encodes a mammalian basic helix-loop-helix transcriptional repressor
      homologous to the products of Drosophila hairy and Enhancer of split. Here, we
      isolated and characterized the mouse Hes2 gene. This gene consists of four exons,
      and all the introns are located within the protein-coding region at positions
      homologous to those of other Hes genes. On the inter-specific backcross analyses,
      mouse Hes2 is mapped to the distal region of Chromosome 4 near the Hes3 and Hes5
      loci, which are different from the Hes1 locus on Chromosome 16. Upstream of the
      transcription initiation site, there are GC-rich regions, but a typical TATA box
      is not present. Transient transfection analyses demonstrated that, while Hes1 and
      Hes5 promoter activities are significantly upregulated by the active form of
      Notch, a key regulator of cellular differentiation, Hes2 and Hes3 promoter
      activities are not. These results suggest that Hes genes are functionally
      classified into two groups: those that are regulated by Notch and those that are
      not.

PMID- 9570951
TI  - Characterization of human and mouse rod cGMP phosphodiesterase delta subunit
      (PDE6D) and chromosomal localization of the human gene.
AB  - The mammalian multisubunit photoreceptor cGMP phosphodiesterase PDE alpha beta
      gamma 2 (PDE6 family) is a peripherally membrane-associated enzyme. A novel
      subunit, termed PDE delta (HGMW-approved symbol, PDE6D; MW 17 kDa), is able to
      detach PDE partially from bovine rod outer segment membranes under physiological
      conditions. Cloning of human and mouse PDE delta cDNAs revealed that PDE delta is
      a nearly perfectly conserved polypeptide of 150 amino acids that shows partial
      sequence homology to photoreceptor RG4 of unknown function. Multiple-species
      Southern blot analysis demonstrates that the PDE delta gene has been well
      conserved during evolution and is detectable at high stringency in invertebrates.
      The human and mouse genes are contained in less than 8 kb of genomic DNA and
      consist of four exons and three introns (0.7-4 kb in human, 0.7-2.2 kb in mouse).
      The PDE delta gene structure is identical to that of the C27H5.1 gene identified
      in the eyeless nematode Caenorhabditis elegans. The human PDE delta gene (locus
      designation PDE6D) was localized to the long arm of chromosome 2 (2q35-q36) by
      fluorescence in situ hybridization. By synteny, the mouse PDE delta gene is
      predicted to reside on chromosome 1.

PMID- 9570952
TI  - Structure and expression of the gene encoding murine M-protein, a sarcomere
      specific member of the immunoglobulin superfamily.
AB  - The complete exon-intron organization of the murine gene encoding M-protein, a
      structural protein of sarcomeric myofibrils, was determined. The gene is composed
      of 37 exons and 36 introns, spanning approximately 75 kb of DNA. Intron positions
      are related to the modular structure of M-protein, which is composed essentially
      of immunoglobulin and fibronectin type III domains. Almost all repeats follow a
      two exon-one domain structure. The beginning and end of each domain are defined
      by introns in phase I; internal introns are more divergent in position and very
      rarely use phase I. A single transcriptional start point was detected in both
      skeletal and cardiac muscle. Analysis of the prospective promoter region revealed
      several potential regulatory elements. CAT expression assays using promoter
      deletion constructs identified three regions that seem to be most important for
      the muscle-specific transcription activation of the M-protein gene. These results
      provide the first complete characterization of a gene for a member of the
      intracellular branch of the immunoglobulin superfamily.

PMID- 9570953
TI  - Characterization of SCML1, a new gene in Xp22, with homology to developmental
      polycomb genes.
AB  - Using exon trapping, we have identified a new human gene in Xp22 encoding a 3-kb
      mRNA. Expression of this RNA is detectable in a range of tissues but is most
      pronounced in skeletal muscle and heart. The gene, designated "sex comb on midleg
      like-1" (SCML1), maps 14 kb centromeric of marker DXS418, between DXS418 and
      DXS7994, and is transcribed from telomere to centromere. SCML1 spans 18 kb of
      genomic DNA, consists of six exons, and has a 624-bp open reading frame. The
      predicted 27-kDa SCML1 protein contains two domains that each have a high
      homology to two Drosophila transcriptional repressors of the polycomb group (PcG)
      genes and their homologues in mouse and human. PcG genes are known to be involved
      in the regulation of homeotic genes, and the mammalian homologues of the PcG
      genes repress the expression of Hox genes. SCML1 appears to be a new human member
      of this gene group and may play an important role in the control of embryonal
      development.

PMID- 9570954
TI  - Identification, characterization, and genetic mapping of Rad51d, a new mouse and
      human RAD51/RecA-related gene.
AB  - Homologous DNA recombination occurs in all organisms and is important for repair
      of DNA damage during mitosis. One of the critical genes for DNA repair and
      meiotic recombination in yeast is RAD51, and homologs of RAD51 have been
      identified in several species, including mouse and human. Here we describe a new
      RAD51-related mammalian gene, named Rad51d, identified by searching the EST
      database with the yeast RAD55 and human RAD51B/REC2 genes. A full-length 1.5-kb
      mouse cDNA clone that encodes a predicted 329-amino-acid protein was isolated.
      Rad51d mRNA was present in every mouse tissue examined. Four different transcript
      sizes were detected, one of which was specific to testis. Human cDNA clones that
      predicted 71% amino acid identity to the mouse protein were also isolated.
      Interestingly, the sequences of these human clones and of RT-PCR-derived products
      provided evidence for alternative splicing. These mRNAs are predicted to encode
      proteins that are truncated relative to the mouse and lack the ATP-binding motif
      characteristic of RecA-related proteins. Using an interspecific backcross mapping
      panel, Rad51d was mapped to mouse Chromosome 11, 48.5 cM from the centromere. By
      radiation hybrid mapping, the human ortholog RAD51D was mapped to chromosome
      17q11, which is a region syntenic to mouse Chromosome 11. Due to its expression
      pattern and sequence similarity to other RAD51 family members, it is likely that
      Rad51d is part of a complex of proteins required for DNA repair and meiotic
      recombination.

PMID- 9570955
TI  - Analysis of homologous XRCC1-linked zinc-finger gene families in human and mouse:
      evidence for orthologous genes.
AB  - Genetic and physical mapping studies indicate that hundreds of zinc-finger (ZNF)
      containing genes populate the human genome and that many of these genes are
      arranged in familial clusters. However, the extent to which these tandemly
      arrayed families are conserved among mammalian species is largely unknown. In a
      previous study, we identified a conserved cluster of Kruppel-associated box
      (KRAB)-containing ZNF genes located near the XRCC1 gene in human chromosome
      19q13.2 and mouse chromosome 7 and analyzed two members of the murine gene
      family, Zfp93 and Zfp94, in detail. Here we report the identification and
      characterization of putative human orthologs of these murine genes. The human
      genes ZFP93 and ZNF45 are substantially similar to their murine counterparts in
      overall structure, but two notable differences exist between the sets of genes.
      First, the human genes encode more ZNF repeats than their murine counterparts.
      Second, the ZNF repeats that are common to orthologs exhibit varying degrees of
      conservation. Expression studies indicate that the human genes, like their mouse
      equivalents, are expressed widely and are coexpressed at similar levels in most
      adult tissues. These comparative gene sequence and expression studies therefore
      suggest that at least two members of the mammalian XRCC1-linked KRAB-ZNF gene
      family were elaborated prior to the divergence of primate and rodent lineages and
      were well conserved in human and mouse.

PMID- 9570957
TI  - The protein kinase N (PKN) gene PRKCL1/Prkcl1 maps to human chromosome 19p12
      p13.1 and mouse chromosome 8 with close linkage to the myodystrophy (myd)
      mutation.
AB  - Protein kinase N (PKN) is a fatty acid- and Rho-activated serine/threonine
      protein kinase involved in the regulation of cell motility by association with
      cytoskeletal components such as neurofilament and alpha-actinin. We determined
      the chromosomal location of the human PKN gene PRKCL1 by fluorescence in situ
      hybridization and by radiation hybrid mapping. The corresponding mouse gene
      Prkcl1 was mapped by segregation analysis. We found by FISH that PRKCL1 is
      localized to chromosome 19p12-p13.1 and, more precisely, by radiation hybrid
      mapping, about 11 cR from EST WI-6344 in subband 19p12. Prkcl1 maps to mouse
      chromosome 8 between D8Mit6 and junb. This region of mouse Chr 8 shows a
      scrambled syntenic conservation to human chromosomes 4q, 8p, and 19p. As the
      mouse mutation myodystrophy myd has been mapped to the same region, Prkcl1 is a
      candidate gene for myd.

PMID- 9570956
TI  - A novel unstable mouse VNTR family expanded from SINE B1 elements.
AB  - Human hypervariable minisatellites provide highly informative loci for analyzing
      processes of tandem repeat turnover, but little is known about mechanisms of
      instability in other species. We have therefore screened the mouse genome for
      analogous VNTR loci. One of the probes we isolated, MMS10, detects a highly
      variable rodent-specific family of multiple loci derived by expansion of a common
      GGCAGA repeat unit from within a subset of B1 short interspersed elements. The
      mean germline mutation rate for loci detected by MMS10 was estimated at 1.7% per
      offspring band, though analysis of individual loci showed substantial variation
      in germinal instability apparently related to repeat array size. This MMS10
      family of expanded hexanucleotide repeat loci provides a novel resource for
      investigating mechanisms of tandem repeat turnover in the mouse and an efficient
      means for monitoring germline mutations induced by external agents such as
      ionizing radiation.

PMID- 9570958
TI  - Cloning of a novel human putative type Ia integral membrane protein mapping to
      21q22.3.
AB  - The distal part of human chromosome 21q22.3 is exceptionally gene rich and
      contains several loci that have been linked to hereditary disorders. In the
      course of constructing an extensive transcript map for chromosome 21, we have
      isolated numerous coding segments in 21q22.3 that represent potential candidate
      genes in this region. Following this approach, we have cloned a novel single-copy
      gene (C21orf3) (HGMW-approved symbol C21orf1) expressed as a unique 2.69-kb mRNA
      in a wide range of tissues. We have precisely mapped C21orf3 by fiber FISH distal
      to marker D21S171. The C21orf3 gene encodes a predicted protein of 180 residues
      that does not share any sequence homology with other known proteins. C21orf3
      harbors predicted structural features of a type Ia integral membrane protein and
      contains a tetrapeptide motif (YXRF) observed in several cell surface proteins
      involved in signal transduction. Although the function of C21orf3 is still
      unknown, this novel gene may play an important role in a cell trafficking
      mechanism.

PMID- 9570959
TI  - Organization of the human glucokinase regulator gene GCKR.
AB  - Glucokinase plays an important role in regulating insulin secretion in response
      to changes in blood glucose levels. As a result, one form of maturity onset
      diabetes of the young (MODY) results from haploinsufficiency of glucokinase. In
      both liver and pancreatic islet, glucokinase is allosterically regulated by an
      inhibitory protein (glucokinase regulatory protein, GCKR). GCKR has therefore
      become an important gene for functional analysis in type 2 diabetes. To allow
      genetic assessment of any such role, we have determined the structure of the
      human GCKR gene. Characterization of P1 and YAC clones containing GCKR shows it
      to consist of 19 exons spanning 27 kb. RT-PCR, RACE, and RNase protection
      experiments defined a transcriptional start site for GCKR 66 bp upstream of the
      initiation codon, but provided no evidence for islet cell specific alternative
      splicing in the rat. By SSCP screening, a common polymorphic sequence variant has
      been defined within exon 15 of human GCKR, at nt 1400 of the cDNA. This alters
      amino acid residue 446 from proline, conserved in rat and Xenopus, to leucine.

PMID- 9570960
TI  - A microdeletion of D6S305 in a family of autosomal recessive juvenile
      parkinsonism (PARK2).
AB  - A gene for autosomal recessive juvenile parkinsonism (ARJP; HGMW-approved symbol
      PARK2; MIM 600116) has recently been mapped to a 17-cM interval on chromosome
      6q25.2-q27. We here report an inbred family with ARJP showing a perfect
      cosegregation with null allele for D6S305, which is a marker within the ARJP
      locus. We assigned the deletion within an interval between D6S1937 and
      AFMa155td9, which are 0 cM apart from each other and located on a single YAC
      clone. Two possibilities should be evaluated: (1) the deletion is polymorphic and
      linked to ARJP and (2) the deletion is pathogenic and contains both D6S305 and
      the ARJP gene (or a part of it). An exon search in a deleted segment or in the
      relatively small-sized genomic clones harboring D6S305 may enormously facilitate
      the cloning procedure of the ARJP gene.

PMID- 9570961
TI  - Structure and chromosomal localization of mouse G protein subunit gamma 4 gene.
AB  - The G protein gamma subunits are members of a multigene family and are implicated
      in determining the specificity of receptor-G protein interaction. The gene
      structures for many of the gamma subunits remain to be determined. Here, we
      report the gene structure for the brain-specific gamma 4 subunit and its map
      position on a mouse chromosome. The gene (Gng4) comprises at least three exons
      spanning over 20 kb. The 225-bp coding region, which spans two exons, is
      interrupted by a large 18.2-kb intron whose position is conserved in other gamma
      subunit genes. There is a putative additional intron in the 5' untranslated
      region just upstream of the translation initiation codon. Introns are present in
      most of the other gamma subunits at this position. The mouse Gng4 gene is mapped
      to chromosome 13.

PMID- 9570962
TI  - Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse
      chromosome 4.
AB  - CYP2J subfamily cytochromes P450 catalyze the NADPH-dependent oxidation of
      arachidonic acid to several unique eicosanoids that possess numerous biological
      activities including modulation of ion transport, control of bronchial and
      vascular smooth muscle tone, and stimulation of peptide hormone secretion. We
      have identified sequence variants in the 3' untranslated regions of two mouse
      Cyp2j genes (Cyp2j5 and Cyp2j6) and used a PCR-based oligonucleotide
      hybridization assay to map both genes to the central region of chromosome 4
      distal to the Jun oncogene. The corresponding human CYP2J gene (CYP2J2) has been
      assigned to human chromosome 1 on a panel of somatic hybrid cell lines and to
      1p31.3-p31.2 by fluorescence in situ hybridization analysis. The proximity of the
      Cyp2j cluster to the Cyp4a cluster suggests that these genes may be part of a
      cassette of P450 genes involved in the oxidation of fatty acids.

PMID- 9570963
TI  - Stch maps to mouse chromosome 16, extending the conserved synteny with human
      chromosome 21.

PMID- 9570964
TI  - The periplakin gene maps to 16p13.3 in human and 16A-B1 in mouse.

PMID- 9570966
TI  - The gene encoding guanidinoacetate methyltransferase (GAMT) maps to human
      chromosome 19 at band p13.3 and to mouse chromosome 10.

PMID- 9570965
TI  - Assignment of the murine Notch2 and Notch3 genes to chromosomes 3 and 17.

PMID- 9570967
TI  - Radiation hybrid mapping of EPB41L1, a novel protein 4.1 homologue, to human
      chromosome 20q11.2-q12.

PMID- 9570968
TI  - Lymphovascular space involvement in cervical cancer: an independent risk factor.

PMID- 9570969
TI  - Influence of quantity of lymph-vascular space invasion on the risk of nodal
      metastases in women with early-stage squamous cancer of the cervix.
AB  - OBJECTIVE: To determine if the quantity of lymph-vascular space invasion
      influences the risk of pelvic nodal metastases in women with early-stage cervical
      squamous carcinoma. METHODS: Between 1991 and 1997, 105 women with stages IA2,
      Ib, and IIa squamous carcinoma of the cervix underwent radical hysterectomy and
      pelvic lymphadenectomy. The histopathology slides were prospectively reviewed. If
      lymph-vascular space invasion (LVSI) was present, the amount was quantified in
      four ways: percentage of cervical histopathologic sections containing LVSI,
      percentage of sections with tumor containing LVSI, total number of foci of LVSI,
      and maximal number of foci of LVSI in 10 high-powered fields. These measures of
      LVSI were correlated with the risk of nodal metastases. RESULTS: Seventy-three
      (70%) women had tumors with LVSI. Of these, 23 had pelvic nodal metastases. All
      women with nodal metastases had tumors with LVSI. Using logistic regession,
      independent predictors of nodal metastases were depth of cervical stromal
      invasion (P = 0.01) and tumor size (P = 0.04). LVSI was also a significant
      predictor of nodal metastases based on the Mantel-Haenszel test (P = 0.01). In
      women whose tumors contained LVSI, logistic regression identified tumor size (P =
      0.004) and LVSI in > 45% of all cervical histopathologic sections (P = 0.002) as
      significant predictors of nodal metastases. CONCLUSION: The quantity of LVSI, as
      defined by the percentage of all cervical histopathologic sections containing
      LVSI, correlates significantly with the risk of nodal metastases in women with
      early-stage squamous carcinoma of the cervix.

PMID- 9570970
TI  - Treatment for fertility and risk of ovarian tumors of borderline malignancy.
AB  - The relationship between fertility drug use and risk of borderline ovarian cancer
      has been analyzed using data from a case-control study. Cases were 93 women aged
      23 to 64 years with histologically confirmed diagnosis of borderline ovarian
      tumor (according to the World Health Organization criteria) who were admitted to
      the Obstetrics and Gynecology Clinics of the University of Milan. Control
      subjects were 273 women (ages 24-64 years) admitted for acute nongynecological,
      nonhormonal, and nonneoplastic conditions. Four cases (4.3%) and no control
      reported fertility drugs use: this difference was statistically significant
      (Fisher's exact test P = 0.004).

PMID- 9570971
TI  - Close vaginal margins as a prognostic factor after radical hysterectomy.
AB  - From 1965 to 1995, at the University of Miami/Jackson Memorial Medical Center,
      1223 patients with stage IA2, IB, or IIA cervical cancer have undergone a radical
      hysterectomy. The charts of these patients were reviewed retrospectively for
      pathology reports showing positive or close surgical margins. Fifty-one of these
      cases had final pathology results interpreted as close vaginal margins (CVM),
      which we define as tumor less than or equal to 0.5 cm from the vaginal margins of
      resection. All slides of blocks with close vaginal margins were found and
      reviewed by a single pathologist. Twenty-eight (54.9%) had parametrial
      involvement or positive lymph nodes and received adjuvant radiation therapy (RT).
      Of the remaining 23 cases, only 6 had other high risk factors, tumor greater than
      4 cm, poorly differentiated, greater than 50% invasion, or lymphovascular space
      involvement. Sixteen of 23 received radiation. The 5-year survival was
      significantly greater with RT, 81.3%, than without RT, 28.6% (P < 0.05). The
      recurrence rate was also decreased from 85.7 to 12.5% (P < 0.01). Although
      present in less than 2% of radical hysterectomy specimens, CVM without other high
      risk factors may be an important prognostic variable that should be considered
      when making adjuvant therapy decisions.

PMID- 9570972
TI  - Prevalence, risk factors, and accuracy of cytologic screening for cervical
      intraepithelial neoplasia in women with the human immunodeficiency virus.
AB  - OBJECTIVES: The objective was to evaluate the sensitivity and specificity of
      cervical cytology in women infected with the human immunodeficiency virus (HIV),
      risk factors for abnormal cytology in HIV-infected and uninfected women, and risk
      factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in
      HIV-infected women. METHODS: Methods included a cross-sectional analysis of
      cervical cytology, colposcopic impression, and histology in 248 HIV-infected
      women and multivariate analyses of risk factors for abnormal cytology in 253 HIV
      infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected
      women. RESULTS: The sensitivity and specificity of cytology for all CIN grades
      were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of
      abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women.
      Independent risk factors for abnormal cytology were immunodeficiency [odds ratio
      (OR) 8-17, P < 0.001] and human papillomavirus (HPV) infection (OR = 5, P <
      0.001). The prevalence of CIN on histology was 32% in HIV-infected women, and the
      only independent risk factor for CIN was oncogenic HPV type (OR = 5, P = 0.005).
      CONCLUSION: Given the high prevalence of abnormal cytology and CIN in HIV
      infected women, cytologic screening has significant limitations. Both
      immunodeficiency and type of HPV infection are important risk factors.

PMID- 9570973
TI  - Unsuspected primary tubal carcinoma during operative laparoscopy.
AB  - OBJECTIVE: To evaluate the possible risk of dealing with an unsuspected primary
      carcinoma of the fallopian tube during laparoscopic surgery. METHODS: We
      performed a countrywide survey in Austria concerning laparoscopic procedures in
      cases of primary carcinoma of the tube. The questionnaire consisted of questions
      regarding the pre-, intra-, and postoperative management. RESULTS: Of 18,435
      laparoscopies in cases of an adnexal mass, 5 cases were reported, when
      laparoscopy was performed on an unsuspected carcinoma of the tube. Therefore, the
      risk of detecting this malignancy during laparoscopy after preoperative
      evaluation is 1 in 3687 cases (0.028%). CONCLUSION: The risk of encountering an
      unsuspected primary carcinoma of the fallopian tube during laparoscopy in Austria
      is an extremely rare situation. In case of a malignancy, a staging or debulking
      laparotomy should be performed immediately or as soon as possible.

PMID- 9570974
TI  - Incidence of ovarian cancer in women with prior hysterectomy in Japan.
AB  - OBJECTIVE: Our aim was to estimate the number of women in Japan in whom ovarian
      cancer could be prevented by performing prophylactic oophorectomy. METHODS: Of
      1289 women who were diagnosed clinically and histologically as having primary
      cancers of the ovary between 1986 and 1995, 53 (4.1%) had undergone hysterectomy
      with conservation of one or both ovaries. Clinical data and representative
      microscopic slides for these 53 cases were evaluated. RESULTS: Hysterectomy had
      been performed at the age 45 or above in 28 of the 53 patients (53%). We
      estimated that performance of prophylactic oophorectomy in women who underwent a
      hysterectomy at age 45 or older would prevent 2.2% (4.1% x 0.53) of the cases of
      ovarian cancer in Japan, which is below the 3.3% estimated for women in other
      countries. The interval between the hysterectomy and the diagnosis of ovarian
      cancer ranged from 1 to 29 years (mean 9.9 years). Fourteen patients (26%)
      developed ovarian cancer within 5 years of the hysterectomy. The overall 3-year
      survival rate of these 53 patients was 65%, not significantly different from that
      for patients with ovarian cancer in the national study in Japan. CONCLUSIONS:
      Prophylactic oophorectomy for the prevention of ovarian cancer in Japanese women
      would appear to have a lesser impact than reported in other industrialized
      nations. The short interval between hysterectomy and the diagnosis of ovarian
      cancer observed in 26% of the patients suggested that ovarian cancer can develop
      within a few years of the visualization of apparently normal ovaries.

PMID- 9570975
TI  - Immunohistochemical expression of thymidine phosphorylase in human endometrial
      cancer.
AB  - OBJECTIVE: To investigate correlations between the expression of thymidine
      phosphorylase (TP) by endometrial cancer cells and the density of microvessels
      within the tumor, the clinicopathologic features, and the prognosis. METHODS: We
      examined tumor specimens obtained from 46 patients with endometrial cancer (9
      FIGO stage IA, 16 stage IB, 8 stage IC, 1 stage IIA, 6 stage IIB, and 6 stage
      IIIC). The cellular expression of TP and the intratumoral density of microvessels
      were determined by immunohistochemistry using monoclonal antibodies to TP and
      factor VIII-related antigen, respectively. We investigated the relationship
      between the cellular expression of TP and the following factors:
      clinicopathologic features (menopausal status, histologic type, tumor size,
      histologic grade, myometrial invasion, cervical invasion, and metastasis), the
      microvessel count, and the disease-free survival period. RESULTS: Of the 46
      tumors, 19 (41%) were TP-positive. The microvessel count was significantly higher
      in TP-positive tumors than in TP-negative tumors (P = 0.01, Mann-Whitney U test).
      There was no significant correlation between TP expression and clinicopathologic
      features, and there was no significant difference in the disease-free survival
      period between patients with TP-positive tumors and patients with TP-negative
      tumors. CONCLUSION: TP expression was not correlated with clinicopathologic
      features or prognosis, but was associated with an increased density of
      microvessels in endometrial cancer. These findings suggest that TP may play an
      important role in angiogenesis and may be involved in the tumorigenesis of
      endometrial cancer.

PMID- 9570976
TI  - Decline in incidence of endometrial cancer following increase in prescriptions
      for opposed conjugated estrogens in a prepaid health plan.
AB  - During the 1980s, the ecologic association of conjugated estrogens with
      endometrial cancer changed from positive to negative in a prepaid health plan.
      During the same period, use of progestins increased dramatically. We investigated
      whether the latter increase could explain the reversal of the estrogen-cancer
      association. Endometrial cancer incidence was estimated from cases recorded in
      the health plan registry divided by the number of women over age 45 years.
      Conjugated estrogens usage was measured as milligrams prescribed per woman per
      year and progestin was measured as tablets per woman per year, both based upon
      pharmacy records. Graphical and regression methods were used to analyze the
      resulting ecologic data. In a log-linear regression of incidence on conjugated
      estrogens and medroxyprogesterone usage, estrogen usage had a strong positive
      association with incidence, while medroxyprogesterone had a strong negative
      association with incidence. The change in the direction of the ecologic
      association between estrogen and endometrial cancer that occurred in 1984
      continued until 1993, suggesting that the decline in endometrial cancer incidence
      and concomitant increase in conjugated estrogens usage since 1984 is explained by
      the increasing use of progestins. The data are entirely consistent with the
      hypothesis that progestins can protect against most of the excess risk conferred
      by conjugated estrogens, although the ecologic nature of the data prohibits
      drawing further inferences.

PMID- 9570977
TI  - A multivariate logistic regression analysis in predicting malignancy for patients
      with ovarian tumors.
AB  - OBJECTIVE: Our objective was to improve the preoperative diagnosis of ovarian
      malignancy using a multivariate logistic regression analysis on the basis of
      demographic, serologic, gray-scale morphological, and Doppler variables. METHODS:
      One hundred seventy-one patients with ovarian tumors (120 benign, 51 malignant
      including 9 tumors of low malignant potential) were studied with transvaginal B
      mode, color, and pulsed Doppler ultrasonography before surgery. Based on the gray
      scale ultrasound imaging, each tumor was classified as a unilocular cyst,
      multilocular cyst, unilocular cyst with solid parts, multilocular cyst with solid
      parts, or solid tumor. Intratumoral blood flow velocity waveforms were recorded
      on all tumors except unilocular cyst and were evaluated for resistance index (RI)
      and peak systolic velocity (PSV). Serum CA 125 levels were also measured.
      RESULTS: Twenty tumors were unilocular cysts and were all benign. Seventy tumors
      including all unilocular cysts which showed no flows were all benign. The
      remaining 101 tumors (50 benign, 51 malignant including 9 tumors of low malignant
      potential) presented intratumoral blood flows. Univariate and multivariate
      logistic regression analyses were conducted to identify variables predictive of
      ovarian malignancy in these 101 tumors. The variables included age, menstrual
      state, serum CA 125 levels, B-mode classification, RI, and PSV. In univariate
      analysis, menopause, the positivity of CA 125 (> or = 35 U/ml), and PSV larger
      than or equal to 10.4 cm/s were found to be significantly associated with
      malignant tumors. The PSV value of 10.4 cm/s was the median in benign tumors.
      Multivariate analysis showed that serum CA 125 levels (> or = 35 U/ml) (P =
      0.002) and PSV (> or = 10.4 cm/s) (P < 0.001) were to be independent predictors
      of malignancy. CONCLUSION: These results suggest that intratumoral PSV is the
      strongest means of differentiating benign from malignant ovarian tumors with
      suspicious gray-scale ultrasonographic findings.

PMID- 9570978
TI  - The value of squamous cell carcinoma antigen as a predictor of nodal metastasis
      in cervical cancer.
AB  - Preoperative serum squamous cell carcinoma antigen (SCC) levels were examined in
      148 cases of stage Ib squamous cervical cancer undergoing radical hysterectomy.
      The effect of the pelvic lymph node status on the marker level was examined by
      comparing 113 cases with cancer limited to the uterus and 23 cases with cancer
      confined to the uterus and pelvic lymph nodes using two different multivariate
      analyses. Ninety-five percent of patients with cancer limited to the uterus
      showed SCC levels of 4 ng/ml or below. Nearly two-thirds (65%) of patients with
      serum levels above 4 ng/ml exhibited pelvic lymph node metastasis. The marker
      values exceeding 4 ng/ml increased the risk of nodal metastasis by eight times,
      compared with serum levels of 4 ng/ml or below. Multivariate analyses confirmed
      that the pelvic lymph node metastasis had a larger impact on the marker level
      than did tumor size or depth of stromal infiltration. SCC levels greater than 4
      ng/ml can be considered a high-risk zone for nodal metastasis.

PMID- 9570979
TI  - Five-year survival after second-line cisplatin-based intraperitoneal chemotherapy
      for advanced ovarian cancer.
AB  - BACKGROUND: To evaluate the 5-year survival rates of second-line intraperitoneal
      chemotherapy in advanced-staged ovarian cancer. MATERIALS AND METHODS: Between
      August 1985 and September 1991, 63 patients with advanced epithelial ovarian
      cancer received intraperitoneal cisplatin and cytarabine chemotherapy as second
      line treatment. RESULTS: The median survival from the time of initiation of
      intraperitoneal chemotherapy (IPC) was 29.1 months. A significant advantage in 5
      year survival (40%) and 5-year progression-free survival (37%) was observed among
      21 patients who demonstrated a response to first-line and second-line treatment
      compared to those who demonstrated a response to first-line treatment only (6 and
      0%, respectively) (P < 0.0001). No patient (n = 13) who failed to respond to
      either first-line or second-line treatment survived for 5 years. Among 42
      patients with < or = 5 mm residual disease at the time of initiation of IPC, 5
      year survival was 36% and 5-year progression-free survival was 31%, while no
      patient (n = 21) with residual disease measuring > 5 mm at the initiation of IPC
      survived 5 years (P < 0.0001). CONCLUSION: Given the limitation that this is not
      a randomized trial, the data appear to indicate that salvage platinum-based
      intraperitoneal chemotherapy results in significant 5-year survival and
      progression-free survival in selected patients who initiated therapy with small
      (< or = 5 mm) tumor burden. These survival rates as second-line therapy approach
      those achieved by first-line platinum-based intravenous chemotherapy in patients
      with advanced-stage ovarian cancer with similar small residual disease at the
      initiation of therapy.

PMID- 9570980
TI  - An analysis of approaches to the management of endometrial cancer in North
      America: a CTF study.
AB  - OBJECTIVE: The aim of this study was to define the clinical-therapeutical
      approach to endometrial cancer now being followed in some of the most important
      centers of reference for gynecological cancer in North America by means of a
      questionnaire. STUDY DESIGN: The questionnaire focused on four principal areas:
      (1) surgical staging and therapy; (2) adjuvant treatment; (3) treatment
      modifications; and (4) management of advanced stages (FIGO III-IV). RESULTS:
      There were 48 evaluable responses (77%) received by the end of December 1994
      which were considered for this analysis. Lymphadenectomy is utilized routinely in
      26/48 centers (54.2%) and in selective clinical-pathological conditions in
      another 21/48 centers (43.5%). In the majority of centers (31/48; 64.6%) radical
      surgery is utilized for selected indications such as cervical involvement. Only
      3/48 (6.2%) centers consider the vaginal approach totally inappropriate. The
      great majority (40/48; 83.3%) of the centers considered postsurgical adjuvant
      therapy to be necessary in FIGO Stage Ic. Brachytherapy is routinely performed in
      3 centers (6.2%) in postsurgical management of Stage I endometrial cancer, while
      the majority of the centers (31/48; 64.6%) perform brachytherapy of the vaginal
      vault in certain clinical-pathological conditions. A wide variety of treatments
      are used for advanced stages (FIGO III-IV). CONCLUSIONS: It emerges that some
      controversial aspects exist on endometrial cancer treatment, and these
      conflicting data need a large-scale multicenter randomized clinical trial.

PMID- 9570981
TI  - Value of glutathione S-transferase pi and the oncogene products c-Jun, c-Fos, c-H
      Ras, and c-Myc as a prognostic indicator in endometrial carcinomas.
AB  - OBJECTIVE: To examine the relationship between the expressions of glutathione S
      transferase pi (GST-pi) and four oncogene products, c-Jun, c-Fos, c-H-Ras, and c
      Myc, and clinicopathological prognostic factors and patients' prognosis in
      endometrial carcinomas, and to assess their prognostic value in endometrial
      carcinomas. METHODS: Specimens of endometrial carcinoma obtained from 63 patients
      were investigated immunohistochemically using respective specific antibodies.
      RESULTS: The overall positive rates in 63 carcinoma specimens were 34.9% for GST
      pi, 44.4% for c-Jun, 34.9% for c-Fos, 47.6% for c-H-Ras, and 54.0% for c-Myc.
      Multivariate analysis revealed that GST-pi expression correlated independently
      with paraaortic lymph node (PAN) metastasis, and c-Jun expression was
      independently related to pelvic lymph node (PLN) and PAN metastasis. The
      prognosis of patients with a GST-pi-positive tumor was significantly poorer than
      that of those with a GST-pi-negative tumor (P < 0.05). The patients with c-Jun
      positive tumor also had a significantly worse prognosis than those with c-Jun
      negative tumor (P < 0.05). No significant relationship between the expressions of
      the remaining three oncogene products, c-Fos, c-H-Ras, and c-Myc, and the
      examined prognostic factors and clinical outcome was apparent. CONCLUSION: These
      results suggest that the expressions of GST-pi and c-Jun may reflect the
      metastatic potential of endometrial carcinomas and that their expressions of
      endometrial carcinoma may be useful as a prognostic indicator for predictive
      testing.

PMID- 9570982
TI  - T-cell-rich B-cell lymphoma and Epstein-Barr virus infection of the uterus in a
      postmenopausal patient with an intrauterine contraceptive device in place for
      over 20 years.
AB  - Although secondary involvement of the female genital tract occurs in up to 40% of
      cases of disseminated lymphomas, lymphomas presenting with primary female genital
      tract symptomatology are very unusual. We report a case of T-cell-rich B-cell
      lymphoma (TCRBCL) arising in the uterine corpus of a 57-year-old female who
      carried an intrauterine contraceptive device (IUD) for over 20 years. Malignant
      lymphoid cells expressed the Epstein-Barr virus (EBV) late membrane protein
      (LMP), a feature described in TCRBCL but not previously reported in primary
      uterine lymphomas. To our knowledge, this is the first reported case of a TCRBCL
      of the uterus.

PMID- 9570983
TI  - Virilizing ovarian tumor of low malignant potential associated with antecedent
      tamoxifen use for breast cancer.
AB  - A patient is described who was treated with tamoxifen for breast cancer and
      developed an androgen-producing ovarian tumor of low malignant potential, which
      itself is a rare condition. Clinically overt virilism was leading to the
      diagnosis and promptly improved after surgical removal of the tumor. A causal
      relationship between tamoxifen use and the tumor is discussed on the basis of the
      known tumor-inducing potential of tamoxifen.

PMID- 9570984
TI  - Vaginal small cell carcinoma mimicking a Bartholin's gland abscess: a case
      report.
AB  - We report a case of a 32-year-old woman with a lesion in the vagina which
      clinically mimicked a Bartholin's gland abscess, but was demonstrated to be a
      small cell carcinoma by light microscopy. This tumor is very rare and to our
      knowledge there are 13 reported cases of primary vaginal small cell carcinoma in
      the English literature. The mean age of presentation of this neoplasm in the 13
      reported cases is 61 with a median survival of 12 months. This case stresses the
      importance of considering this unusual diagnosis when confronted with a large or
      recurrent "Bartholin's gland lesion," and underlines the need for careful
      pathological examination of such specimens.

PMID- 9570985
TI  - Myxoid change in nondecidualized cutaneous endometriosis resembling malignancy.
AB  - Cutaneous endometriosis infrequently arises in the absence of pelvic disease.
      Rare features such as myxoid change can resemble malignancy and may pose a
      challenging histological diagnosis. We are not aware of any previous cases
      involving nondecidualized cutaneous endometriosis with myxoid change associated
      with an abdominal surgical scar. We report the first such case in which a 24-year
      old woman presented with a steadily growing, firm, tender, painful, subcutaneous
      cicatrical mass that had appeared shortly after cesarean section 1 year
      previously. The mass was removed and permanent sections revealed foci of large,
      irregular endometrial glands embedded within prominent myxoid stroma and
      acellular mucin pools, with fibrosis and pseudoinfiltration of the fascia. No
      evidence of malignancy was identified. This case demonstrates that
      nondecidualized cutaneous endometriosis with myxoid change should be considered
      in the differential diagnosis of histologically similar malignancies such as
      mucinous adenocarcinoma and pseudomyxoma peritonei.

PMID- 9570986
TI  - An HIV-infected woman with choriocarcinoma presenting with a nasal mass.
AB  - Gestational choriocarcinoma metastasized to the nasal mucosa is extremely rare.
      An HIV-infected woman with choriocarcinoma presenting with a nasal mass is
      reported. The clinical findings are compared with a previous reported case. She
      responded to multiagent chemotherapy and has obtained complete remission. The
      role of HIV infection is also discussed.

PMID- 9570987
TI  - Volume 65, Number 3 (1997), in Article No. GO974699, "Prospective Study to
      Compare Endometrial Cytology and Transvaginal Ultrasonography for Identification
      of Endometrial Malignancies," by Hiroshi Tsuda, Masami Kawabata, Kumio Yamamoto,
      Takeshi Inoue, and Naohiko Umesaki, pages 383-386:
AB  - Copyright

PMID- 9570989
TI  - Small cystic pelvic masses in older women: is surgical removal necessary?

PMID- 9570990
TI  - The malignant potential of small cystic ovarian tumors in women over 50 years of
      age.
AB  - OBJECTIVE: The aim of this study was to determine the risk of malignancy in
      cystic ovarian tumors < 10 cm in diameter in asymptomatic postmenopausal women or
      women >or =50 years of age. METHODS: All cystic ovarian tumors detected by
      transvaginal sonography screening in asymptomatic postmenopausal women or women >
      or =50 years of age were evaluated with respect to size and morphology. Histology
      was recorded on all tumors removed surgically. Follow-up data were available both
      on patients undergoing surgery and on those who elected to be followed without
      operative intervention. RESULTS: Unilocular cystic tumors were detected in 256 of
      7705 patients (3.3%). All tumors were < 10 cm in diameter and 90% were < 5 cm in
      diameter. One hundred twenty-five of these cysts (49%) resolved spontaneously
      within 60 days and 131 (51%) persisted. Forty-five patients with persisting
      ovarian cysts underwent operative removal of these tumors. Thirty-two patients
      had ovarian serous cystadenomas, and the remainder had a variety of benign
      lesions. There were no cases of ovarian carcinoma in this group. Eighty-six
      patients with unilocular cystic ovarian tumors were followed at 3- to 6-month
      intervals without surgery, and none have developed ovarian cancer. Complex cystic
      ovarian tumors were detected in 250 patients (3.2%). All tumors were < 10 cm in
      diameter and 89% were < 5 cm in diameter. One hundred thirty-five (55%) resolved
      spontaneously within 60 days, and 115 (45%) persisted. One hundred fourteen of
      these patients underwent operative tumor removal. Seven patients had ovarian
      carcinoma, 1 had primary peritoneal cancer, and 1 had metastatic breast cancer to
      the ovary. CONCLUSION: Unilocular ovarian cysts < 10 cm in diameter in
      asymptomatic postmenopausal women or women > or =50 years of age are associated
      with minimal risk for ovarian cancer. In contrast, complex ovarian cysts with
      wall abnormalities or solid areas are associated with a significant risk for
      malignancy. These data are important in determining optimal strategies for
      operative intervention in these patients.

PMID- 9570991
TI  - Surgery for cervical cancer: a time for reassessment.

PMID- 9570992
TI  - Heat shock protein 27: an independent prognostic indicator of survival in
      patients with epithelial ovarian carcinoma.
AB  - OBJECTIVE: Heat shock protein 27 (HSP27) is produced in response to
      pathophysiologic stress in animal cells. The purpose of this study was to
      determine prospectively whether HSP27 was associated with known prognostic
      factors as well as survival in patients with epithelial ovarian carcinoma.
      METHODS: Ninety-nine patients with epithelial ovarian carcinoma were studied.
      Slides were prepared from fresh tissue. Patient records were examined for FIGO
      stage, grade, histology, level of cytoreduction, and survival. RESULTS:
      Immunohistochemical staining for HSP27 was not related to histologic grade, level
      of cytoreduction or histologic subtype. A statistically significant difference in
      HSP27 staining was found in relation to FIGO stage (P = 0.013). HSP27 staining
      was found to be an independent predictor of 2-year survival in these patients (P
      = 0.041). CONCLUSION: The level of HSP27 significantly decreases as the FIGO
      stage increases and is an independent prognostic indicator of survival in
      patients with epithelial ovarian carcinoma.

PMID- 9570993
TI  - A phase II trial of intraperitoneal cisplatin and etoposide as consolidation
      therapy in patients with Stage II-IV epithelial ovarian cancer following negative
      surgical assessment.
AB  - PURPOSE: To determine the efficacy of three courses of intraperitoneal (i.p.)
      cisplatin (CDDP) and etoposide (VP-16) as consolidation therapy following
      pathologically negative second-look surgical reassessment for Stage IIC-IV
      epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Between September 1988 and
      April 1996, 40 patients were treated with three cycles of i.p. CDDP (100
      mg/m2)/VP-16 (200 mg/m2) as consolidation therapy. Survival was compared to that
      of a group of 46 contemporaneous patients undergoing observation only. RESULTS:
      Median age of the 36 eligible patients was 52 years (range 30-70 years). Stage
      distribution was II (3), III (31), and IV (2); histologic grade was 1 (2), 2 (7),
      3 (25), and not recorded (2); and residual disease at completion of initial
      surgery was none/microscopic in 13/36 (36%) patients. Median age of the 46
      patients who did not receive consolidation was 52 years (range, 27-80 years);
      stage distribution was II (18), III (26), and IV (2); histologic grade was 1 (5),
      2 (12), 3 (28), and not recorded (1). With a median follow-up of 36 months in
      both groups, 14/36 (39%) of the protocol group have recurred compared with 25/46
      (54%) of those undergoing observation alone. Median disease-free survival (DFS)
      for the observed patients is 28.5 months and has not been reached in the
      consolidation group. Disease-free survival distribution between the two groups
      was compared using the log-rank test and was found to be significant (P = 0.03).
      Multivariate analysis revealed that the only significant predictor of improved
      DFS was protocol treatment (P < 0.01). CONCLUSION: Intraperitoneal consolidation
      with CDDP/VP-16 following negative second-look reassessment in patients with
      advanced EOC resulted in a significant increase in DFS compared to nonprotocol
      patients treated concurrently who underwent observation alone.

PMID- 9570994
TI  - Imbalanced expression of inhibin and activin subunits in primary epithelial
      ovarian cancer.
AB  - OBJECTIVES: Inhibins and activins are related gonadal peptides with opposing
      biologic actions on gonadotropin regulation, cell differentiation, and
      proliferation. The previous study of activin in ovarian cancer cell lines
      suggests that activin may promote growth of ovarian cancer. Elevated serum
      inhibin levels were also found in ovarian cancer patients; however, the source of
      elevated inhibin is unknown. This study is designed to examine the expression of
      inhibin and activin subunits as well as activin receptor in primary ovarian
      epithelial tumors to explore their role in the process of ovarian epithelial
      tumorigenesis. METHODS: The protein and mRNA expression of alpha and betaA
      subunits of inhibin/activin as well as of activin receptor mRNA were examined
      with immunohistochemistry (IHC) and reverse transcription-polymerase chain
      reaction (RT-PCR) in 112 ovarian carcinomas. Cases included 59 serous, 23
      endometrioid, 16 mucinous, 9 clear cell, and 5 undifferentiated carcinomas. We
      also tested normal ovary and benign and borderline ovarian tumors for comparison.
      These included 17 ovarian surface epithelial samples, 6 serous and 5 mucinous
      cystadenomas, and 9 serous and 7 mucinous tumors of low malignant potential. A
      total of 139 ovarian tumors were analyzed by IHC and a total of 63 ovarian tumor
      samples were tested by RT-PCR. RESULTS: Inhibin alpha subunit expression was
      found in 47% of ovarian surface epithelia and focal alpha immunoreactivity was
      seen in tumor stroma, but was not found in the epithelial component of ovarian
      cystadenomas, tumors of low malignant potential (LMP), or carcinomas. Activin
      betaA subunit was expressed in 93% of surface epithelia, in the epithelial
      component of all cystadenomas, in 81% of LMP tumors, and in 72% of carcinomas,
      but not in tumor stroma. Activin expression did not correlate with histologic
      grades, tumor types, and surgical stages. Activin receptor type I and II mRNA
      amplified products were found in virtually all the surface epithelial samples and
      ovarian tumors. CONCLUSIONS: The data suggest that imbalanced expression of
      inhibin and activin subunits in ovarian surface epithelium may represent an early
      event which leads to epithelial proliferation. Unopposed betaA and activin
      receptor expression in epithelial compartment of ovarian tumors suggest that
      activin may be available as autocrine and/or paracrine factors in ovarian
      epithelial tumors. But exact roles of inhibin and activin in ovarian epithelial
      tumors remain to be defined.

PMID- 9570995
TI  - Laparoscopic placement of PAP catheters for intraperitoneal chemotherapy in
      ovarian carcinoma.
AB  - OBJECTIVE: To our report our experience with the laparoscopic placement of
      peritoneal access ports and to compare it to our experience with placement at
      laparotomy. METHODS: Patients with advanced ovarian carcinoma were enrolled in a
      study to receive intraperitoneal paclitaxel in combination with intravenous
      cisplatin and cyclophosphamide as first- or second-line chemotherapy. Patients
      had a PAP catheter placed at primary laparotomy or by a separate laparoscopic
      procedure under general anesthesia. RESULTS: In 13 patients a PAP catheter was
      placed during primary laparotomy, without complications. Thirteen patients had
      laparoscopic catheter placing, using routine Veress needle insufflation. After a
      bowel perforation at insertion of the umbilical trocar had occurred in one
      patient, due to extensive adhesions, we decided to use only an open laparoscopic
      procedure. No other procedure or catheter-related complications occurred.
      CONCLUSION: Laparoscopic-assisted placement of PAP catheters is feasible, but
      should preferably be performed by an open laparoscopic procedure in this patient
      population at risk for intraabdominal adhesions.

PMID- 9570996
TI  - Palliative benefit of external-beam radiation in the management of platinum
      refractory epithelial ovarian carcinoma.
AB  - In vitro studies and clinical experience have suggested that patients with
      platinum-refractory epithelial ovarian carcinoma exhibit cross-resistance to
      radiation. Salvage with radiation in these patients is rare. However, radiation
      is often utilized to palliate symptoms caused by these chemotherapy-resistant
      tumors. Forty-seven patients with platinum-refractory epithelial ovarian
      carcinoma were referred for palliative radiation and 33 (70%) were evaluable for
      response. One to four regimens of platinum-based chemotherapy (median 2.7) were
      given to each patient prior to radiation therapy. Of the 33 evaluable patients,
      23 (69.7%) had a complete resolution of symptoms after radiation, 8 (24%) had a
      partial resolution, and 2 were unassessable because of unrelated medical
      complications. The median duration of response was 11 months (range 1-86) and
      closely approximated their survival. Thirteen of 33 patients (39%) obtained
      relief of symptoms for greater than 12 months, with 10 of 33 (30%) having
      symptoms controlled for 6 to 12 months. In only 10 patients (30%) was the
      duration of palliation less than or equal to 6 months. Four patients required
      reirradiation to the same area for recurrence of their symptom. External-beam
      radiation therapy can provide effective and durable palliation of symptoms in
      platinum-refractory epithelial ovarian carcinoma patients.

PMID- 9570997
TI  - Endometriosis with massive ascites.
AB  - We present 4 cases of endometriosis complicated by massive ascites from our
      institution and a review of 27 cases from the literature. In most of these
      patients, the presence of ascites with its related symptoms in association with
      pelvic masses suggested a neoplastic disease. However, a large proportion of
      these women had also classical manifestations of endometriosis, e.g.,
      dysmenorrhea, cul-de-sac nodularities, and exacerbation of ascites and other
      symptoms during the menses. The response to hormonal therapy including GnRH
      agonists was often unsatisfactory. Repeat recurrences and severe complications
      required multiple laparotomies and thoracotomies for associated pleural and
      pulmonary involvement.

PMID- 9570998
TI  - HPV-16-related proteins as the serologic markers in cervical neoplasia.
AB  - OBJECTIVE: Recently, a variety of HPV-related proteins have been synthesized and
      their utility as diagnostic and prognostic markers in cervical cancers needs to
      be assessed. The ability to generate preparative amounts of HPV-16 L1/L2 VLPs and
      E6, E7 proteins may have implications for the development of a serologic assay to
      detect anti-HPV-16 virion immune responses. The purpose of the study is to
      improve the way of proper management of the cervical cancer by investigating the
      utility of the recently developed HPV-16 L1/L2 VLPs, HPV-16 E6, E7 proteins as
      the clinical serologic markers through antibody reactions by comparison with
      those of SCCA and CEA which have been used as tumor markers for cervical cancer.
      METHODS: The serologic responses in Korean women with cervical neoplasia by ELISA
      using HPV-16 L1/L2 VLPs and radioimmunoprecipitation assay (RIPA) using in vitro
      translated HPV-16 E6, E7 proteins were investigated. PCR using E6 type-specific
      primers for HPV-16/18 was used to determine the presence and type of HPV
      infection (normal controls, 15 cases; preinvasive lesions, 28 cases; invasive
      cervical cancers, 124 cases). RESULTS: The sera of 34% (42/124) of cervical
      cancers were positive for SCCA and the sera of 18% (22/124) of cervical cancers
      were positive for CEA. The positivity of SCCA was increased with advancing
      clinical stages, but the antibody levels were not correlated with clinical stage
      of disease. The sera of 7% (1/15) of normal controls, 39% (11/28) of preinvasive
      lesions, and 56% (70/124) of patients with cervical cancer were ELISA positive
      for HPV-16 L1/L2 VLPs (P < 0.05). The sera of 7% (2/28) of preinvasive lesions
      and 51% (63/124) of cervical cancers were positive for in vitro translated HPV-16
      E6 protein (P < 0.05) and the sera of 11% (3/28) of preinvasive lesions and 33%
      (41/124) of cervical cancers were positive for in vitro translated HPV-16 E7
      protein (P < 0.05). The antibody levels to HPV-16 E7 protein were correlated to
      clinical stage and tumor burden in a significant number of cervical cancers.
      CONCLUSIONS: These data suggest that a considerable number of patients with
      cervical neoplasia generated positive antibody response to L1/L2 VLPs and in
      vitro translated E6, E7 proteins of HPV-16. These HPV-16-associated proteins
      might be disease-specific markers which could be useful in an adjunctive
      diagnostic assay and a seroepidemiologic study of HPV-related cervical neoplasia.
      In particular, the monitoring of antibody to HPV-16 E7 protein seems to be
      valuable in the proper management of cervical cancers for specific tumor markers.

PMID- 9570999
TI  - Estimation of probability of malignancy using a logistic model combining physical
      examination, ultrasound, serum CA 125, and serum CA 72-4 in postmenopausal women
      with a pelvic mass: an international multicenter study.
AB  - BACKGROUND: To assess the differential diagnostic potential of physical
      examination, ultrasound, the serum CA 125 assay, and serum CA 72-4 assay, and the
      contribution of each parameter to a logistic model predicting the probability of
      malignancy in postmenopausal patients presenting with a pelvic mass. PATIENTS AND
      METHODS: In a multicenter, prospective study a total of 155 patients were
      evaluated preoperatively using a standard protocol for pelvic examination,
      transvaginal (occasionally additional abdominal) ultrasound, and serum CA 72-4
      (cutoff level 3 U/ml) and CA 125 (cutoff level 35 U/ml). RESULTS: Fifty-nine
      malignant (39%) and 92 benign (61%) pelvic tumors were found in addition to 4
      borderline tumors (3%). Forty-three patients appeared to have ovarian carcinoma,
      FIGO Stage III or IV in 28 cases. Borderline tumors were excluded from the
      statistical calculations. The diagnostic accuracy of each single parameter, i.e.,
      pelvic examination, ultrasound, and serum CA 125 and CA 72-4 in discriminating
      between benign and malignant pelvic masses gave highly similar results (81, 76,
      78, and 81% respectively). Best sensitivity was found in pelvic examination
      (92%); best specificity was found in CA 72-4 (93%). Using logistic regression
      analysis the power of pelvic examination appeared to be the most relevant
      (adjusted odds ratio 12.1), followed by ultrasound (odds ratio 9.7), serum CA 125
      (odds ratio 5.0), and serum CA 72-4 (odds ratio 4.9). Age appeared to be
      nonpredictive. The logistic model gives a correct prediction in 87% of all cases.
      CONCLUSIONS: The addition of serum CA 72-4 to the combination of pelvic
      examination, ultrasound, and serum CA 125 leads to an improved discrimination
      between malignant and benign pelvic masses.

PMID- 9571000
TI  - Concomitant endometrial hyperplasia in patients with endometrial carcinoma.
AB  - OBJECTIVES: The aim of this study was to compare the histopathologic features and
      prognosis of patients with endometrial carcinoma with and without concomitant
      hyperplasia. METHODS: Histologic slides of the surgical specimens of 214
      consecutive patients who underwent surgery as primary treatment for endometrial
      carcinoma from 1985 through 1991 were reviewed. RESULTS: Ninety-two of the 214
      patients (43%) with endometrial carcinoma had concomitant endometrial
      hyperplasia. Patients with endometrial carcinoma with hyperplasia were
      significantly younger than those without hyperplasia (mean age 62 +/- 10 vs 65 +/
      9 years, P < 0.05). Carcinomas associated with hyperplasia were better
      differentiated and of lower surgical stage. By univariate analysis the frequency
      of recurrence was significantly lower (4% vs 17%, P < 0.004) and the estimated 5
      year survival rate significantly higher (96% vs 85%, P < 0.01) in patients with
      endometrial carcinoma with concomitant hyperplasia. However, in multivariate
      analysis the presence of endometrial hyperplasia was not an independent
      prognostic factor and the 5-year survival rates of patients with or without
      hyperplasia did not differ significantly in any surgical stage. CONCLUSION: The
      presence or absence of concomitant endometrial hyperplasia is strongly correlated
      with the surgical stage of endometrial carcinoma.

PMID- 9571001
TI  - Uterine papillary serous carcinoma: evaluation of long-term survival in
      surgically staged patients.
AB  - OBJECTIVE: Earlier studies have demonstrated that the uterine papillary serous
      carcinoma (UPSC) variant of endometrial carcinoma has a high recurrence rate,
      even when disease is apparently confined to the uterus. The current study
      evaluated survival in patients with surgically staged UPSC. METHODS: Patients
      with UPSC were identified from surgical pathology files and charts were
      retrospectively reviewed. Only patients who had undergone a TAH-BSO, lymph node
      dissection, and peritoneal cytology were included. RESULTS: The FIGO stages of
      the 36 patients were 12 Stage I (4 IA, 4 IB, 4 IC), 2 Stage IIB, 13 Stage III (5
      IIIA, 8 IIIC), and 9 Stage IV. Of the 14 Stage I/II patients, 6 did not receive
      adjuvant therapy, 5 received whole pelvic radiation (WPXRT), and 3 received whole
      abdominal radiation therapy (WART); after a median follow-up interval of 50
      months only 2 (14%) of these Stage I/II patients have developed a recurrence.
      Both of the recurrences were in Stage IC patients who received radiation; 1
      recurred in the radiation field. Of the 5 Stage IIIA patients, 3 patients
      declined therapy and 2 were treated with WART; 3 patients, including the 2 who
      received radiation therapy, are alive without disease. Of the 8 Stage IIIC
      patients, 2 declined postoperative therapy, 2 received WART, and 4 received WPXRT
      with an extended field to include paraaortic nodes. Four of the 6 Stage IIIC
      patients treated with curative intent are without evidence of disease and 1 died
      of unrelated causes after a median follow-up interval of 48 months. Both of the
      Stage IIIC patients who declined treatment recurred. Of the 9 patients with Stage
      IV disease, 8 have died of disease. CONCLUSION: Women with UPSC have a good
      prognosis when surgical staging confirms that disease is confined to the uterus
      (Stage I/II). Surgical findings can also be used to tailor adjuvant radiation
      treatments. Further study is required to define the optimal treatment for women
      with metastatic UPSC.

PMID- 9571002
TI  - Endometrial adenocarcinoma with trophoblastic differentiation.
AB  - OBJECTIVE: To report a case of stage IIIc poorly differentiated endometrial
      adenocarcinoma with trophoblastic differentiation and to review previously
      reported cases. METHODS: The clinical course and histopathology of the case were
      reviewed, and a literature search for other reported cases was performed.
      RESULTS: The tumor contained syncytiotrophoblast-like giant cells that stained
      positively for the beta subunit of human chorionic gonadotropin (beta-hCG), and
      the patient's serum beta-hCG level was elevated (95 mIU/ml), but became
      undetectable after treatment. Beta-hCG was used as a tumor marker during further
      therapy. At 16 months' survival, she remains without evidence of disease and with
      a beta-hCG (level < 5 mIU/ml). Nine other cases of trophoblastic differentiation
      in gynecologic nontrophoblastic tumors have been reported, five in endometrial
      carcinomas which we review. CONCLUSIONS: Trophoblastic differentiation in
      gynecologic nontrophoblastic tumors is rare. Beta-hCG may be useful as a tumor
      marker in these cases. The clinical behavior of these tumors has been aggressive,
      with advanced stages at diagnosis, early widespread metastases or recurrences and
      poor patient outcomes. The patient presented in this report, however, remains
      without evidence of disease 16 months following diagnosis and may be the longest
      survivor with this tumor reported to date.

PMID- 9571003
TI  - Embryonal rhabdomyosarcoma of the uterine cervix: case report and review of the
      literature.
AB  - Embryonal rhabdomyosarcoma (RMS) of the female genital tract usually occurs
      during childhood in the vagina. In rare cases, RMS can originate in the uterine
      cervix, with a peak incidence in the second decade. A combined modality approach
      to treating RMS using multidrug chemotherapy, radiotherapy, and surgery has
      markedly improved survival. Early stage embryonal RMS of the cervix has been
      found to have an excellent prognosis. The present case and literature review
      indicate that extensive surgery does not improve survival in patients with stage
      I disease.

PMID- 9571005
TI  - IXth World Congress on Gestational Trophoblastic Diseases
AB  - Copyright

PMID- 9571004
TI  - Lobular breast carcinoma metastatic to the vulva: a case report and literature
      review.
AB  - BACKGROUND: Six previous reports have documented a vulvar metastasis from breast
      cancer; one has noted involvement of the Bartholin's gland. CASE: A 53-year-old
      woman presented with an enlarging vulvar mass. Evaluation also identified a
      breast lesion. Surgical excision confirmed an invasive lobular breast carcinoma
      with a distant metastatic focus on the vulva. CONCLUSION: This is the first
      report in the English literature to document a vulvar metastasis from an invasive
      lobular carcinoma and the second to identify involvement of the Bartholin's
      gland. Careful gynecologic surveillance is needed in women with breast cancer.

PMID- 9571008
TI  - Growth hormone increases aggressive behavior in juvenile rainbow trout.
AB  - The aim of the present study was to clarify the role of growth hormone in social
      interactions in juvenile salmonids. Growth hormone increases the metabolic
      demands and feeding motivation in teleost fish. As a consequence, growth hormone
      may increase aggression levels and/or fighting ability. To test these hypotheses
      we observed agonistic behavior in pairs of juvenile rainbow trout (Oncorhynchus
      mykiss) consisting of two control fish (C/C pairs), two growth hormone-treated
      fish (GH/GH pairs), or one growth hormone-treated and one control fish (C/GH
      pairs). The initiator and the winner of each act of aggression were registered.
      Aggression was lowest in the C/C pairs, intermediate in the C/GH pairs, and
      highest in the GH/GH pairs, with the difference between the C/C pairs and the
      GH/GH pairs being significant. This supports the hypothesis that GH increases
      aggression levels. However, in the C/GH pairs, the number of conflicts won by GH
      treated and control fish did not differ significantly. Thus, because social
      status was not increased, GH did not appear to affect fighting ability. We
      suggest that growth hormone affects aggression indirectly by increasing the
      swimming activity, and/or by inducing defense of a larger territory, thereby
      increasing the encounter rate between opponents. Since increased aggression can
      incur energetic and mortality costs, there may be selection against high GH
      levels in natural populations.

PMID- 9571007
TI  - Hormones and external factors: are they "on/off" signals for maternal nest
      building in rabbits?
AB  - Estradiol, progesterone, and prolactin regulate digging, carrying straw, and
      plucking hair for maternal nest-building in rabbits. To explore whether external
      factors also modulate this process, we assessed whether shaved pregnant rabbits
      with straw nests would collect their own, male, or synthetic hair for nest
      building. Pregnant (but not estrous) does collected and used all hair types,
      indicating that hair-plucking can be bypassed and a nest constructed with
      "alternative" hair. Unshaved pregnant does with straw nests also collected
      synthetic hair, indicating that this behavior is not triggered by the absence of
      maternal hair. Yet, if hair-plucking/nest-building had occurred, hair-collecting
      was prevented, suggesting that an internally triggered "drive" was turned off by
      perceiving a built nest. When given only straw or hair, shaved pregnant does
      collected and used the material provided, indicating that nest-building is
      internally driven and accomplished by using any available elements. When given
      both materials, increasingly more shaved does built straw nests across prepartum
      days 7 to 2. Straw-carrying declined thereafter, suggesting that perceiving a
      straw nest limits the collection of such material. Hair-collecting was postponed
      until prepartum day 1 to postpartum day 2, indicating that: (a) mothers
      distinguish between straw and hair and (b) hormonal factors regulate the
      sequential selection of straw and then hair and when the change from straw to
      hair occurs. Maternal behavior was normal at parturition and for the next 4 days
      in a similar proportion of does among all experimental groups. We conclude that
      hormones and external factors regulate nest-building by acting as "on/off/on"
      signals.

PMID- 9571009
TI  - Central opioid control of feeding behavior in the white-crowned sparrow,
      Zonotrichia leucophrys gambelii.
AB  - Many behavioral responses to stress do not appear to be mediated by
      glucocorticoids, suggesting another mechanism. We tested the effects of
      intracerebroventricular administration of beta-endorphin, a neuropeptide
      implicated in the stress response, on feeding behavior in captive, wild-caught
      white-crowned sparrows (Zonotrichia leucophrys gambelii). The amount of time
      spent feeding and the number of feeding bouts were higher after infusion with
      beta-endorphin than after saline infusion. Beta-endorphin decreased the latency
      to feed compared with saline. Naloxone, an opioid antagonist, suppressed feeding
      behavior and increased latency to feed. These results support our hypothesis that
      neuropeptides associated with stress may initiate adaptive responses to natural
      stressors in wild species.

PMID- 9571010
TI  - Estrogen implants in the medial preoptic area stimulate maternal behavior in male
      rats.
AB  - The present study investigated whether the medial preoptic area (MPOA) mediates
      estrogen stimulation of maternal behavior in the male as it does in the female.
      Previous studies have shown that lesions of the medial preoptic area prevent
      sensitization of maternal behavior in male rats and that in gonadectomized,
      hormonally primed males, systemically administered estradiol benzoate stimulates
      short-latency maternal behavior. These findings are similar to those found in
      females. In the present study adult males were gonadectomized and hormonally
      primed with subcutaneously implanted capsules of estradiol (Days 1-16) and
      progesterone (Days 3-15) and then were stereotaxically implanted bilaterally in
      the MPOA with implants containing 10% estradiol. Tests with young pups were
      started 48 h later and continued for 10 days (11 tests). Control groups were
      implanted in the MPOA with cholesterol or were injected subcutaneously with
      estradiol benzoate (100 microg/kg). Estradiol implanted males had shorter
      latencies for maternal behavior (retrieving, crouching, licking pups) than
      cholesterol implanted males, but their latencies were slightly longer than those
      of estradiol benzoate injected males. The medial preoptic area, therefore,
      mediates estrogen stimulation of maternal behavior in males as it does in
      females.

PMID- 9571011
TI  - Activities of aromatase and 3beta-hydroxysteroid dehydrogenase/delta4-delta5
      isomerase in whole organ cultures of tissues from developing zebra finches.
AB  - The hormonal basis for masculine song development in the zebra finch remains
      unidentified. To understand how steroids are differentially supplied to the
      brains of males and females to cause sexually dimorphic development of this
      behavior, we have studied the steroidogenic capability of zebra finch tissues
      during early development (1 to 8 days posthatching). Here, we report on the use
      of cultures of whole gonads, adrenals, and telencephalons to measure the
      activities of two steroidogenic enzymes: aromatase, the enzyme that catalyzes the
      conversion of androgen to estrogen, and 3beta-hydroxysteroid dehydrogenase/delta4
      delta5 isomerase (3beta-HSD), the enzyme that converts pregnenolone into
      progesterone. We also examined the effect of cAMP on aromatase activity in these
      tissues as this intracellular second messenger has been shown previously to
      regulate aromatase in both central and peripheral tissues of other species. In
      untreated cultures, aromatase was detected at the highest levels in male and
      female telencephalon and in ovary. Dibutyryl (dB)-cAMP had no significant effect
      on aromatase activity in any tissue. However, after dB-cAMP treatment, estrogens
      were regularly detected in cultures of whole testes. Although this activity was
      relatively low when compared to total activity found in other tissues, due to the
      small size of the testes at this age of development, the specific activity (per
      milligram of protein) might be high enough to produce some estrogen. Adrenal
      aromatase was unconfirmed in the presence or absence of cAMP. 3Beta-HSD activity
      was undetected in brain but was detected in gonads and adrenals from all birds.
      There were no significant differences in gonadal or adrenal 3beta-HSD activity
      between males and females. Although these data present the first evidence for
      testicular aromatase in the zebra finch, they provide no evidence to support a
      mechanism to generate a greater estrogenic signal in male zebra finches after
      hatching.

PMID- 9571012
TI  - Hormones and territorial behavior during breeding in snow buntings (Plectrophenax
      nivalis): an Arctic-breeding songbird.
AB  - We examined hormonal profiles and behavior associated with maintaining a single
      purpose territory in an Arctic-breeding songbird-the snow bunting (Plectrophenax
      nivalis). Snow buntings differ from many other Arctic-breeding passerines by
      using nest cavities, an uncommon and defended resource, but not relying upon the
      surrounding territory for forage. Circulating levels of testosterone in males
      were high when territories were established and then decreased over the breeding
      season. LH secretion was enhanced in females while laying eggs, followed by
      detectable levels of estradiol during incubation. Both sexes showed equivalent
      corticosterone responses to the stress of being captured and held. Male snow
      buntings vigorously defended territories in response to a simulated territorial
      intrusion both when initiating breeding and when feeding young. Exogenous
      testosterone implants surprisingly inhibited physical aggression but enhanced
      singing when birds were feeding young, thus suggesting that song and physical
      aggression are mediated by different hormonal mechanisms at this time of year.
      Together, these results contrast with hormonal profiles and behavior in other
      Arctic-breeding passerines.

PMID- 9571013
TI  - Testosterone augments neuronal Fos responses to estrous odors throughout the
      vomeronasal projection pathway of gonadectomized male and female rats.
AB  - Pheromonal signals emanating from female rats' soiled bedding have previously
      been shown to attract male conspecifics and to augment the number of Fos
      immunoreactive neurons present in portions of the vomeronasal projection pathway,
      ranging from the accessory olfactory bulb (AOB) to the medial preoptic area
      (mPOA) of gonadectomized, testosterone-treated male as well as female subjects.
      In the present study we extended these findings by showing that these neuronal
      Fos responses to estrous odors occurred only in gonadectomized subjects which
      received testosterone propionate (TP), as opposed to oil vehicle, at the time of
      testing. Previously, when treated with TP, all subjects had displayed mounting
      with an estrous female. In subsequent tests, gonadectomized male and female
      subjects spent significantly more time investigating soiled estrous bedding as
      opposed to clean or anestrous bedding, again, provided they were receiving TP. We
      propose that testosterone facilitates odor-induced neuronal Fos expression either
      via its conversion to estradiol, and the subsequent action of this steroid at
      estrogen response elements on the c-fos gene, or via some indirect mechanism
      involving centrifugal control of AOB neurotransmission. The ability of female
      odors to stimulate equivalent numbers of Fos-IR cells in gonadectomized, TP
      treated male and female rats indicates that the functional responsiveness of
      neurons throughout the vomeronasal projection pathway is made more male-like by
      the fetal actions of testosterone in female as well as in male rats. Previous
      studies established that males have more neurons than females in several segments
      of the vomeronasal pathway; however, this morphological sexual dimorphism does
      not account for the observed isomorphic neuronal Fos responses to female odors.

PMID- 9571014
TI  - Suppression of cortisol levels in subordinate female marmosets: reproductive and
      social contributions.
AB  - Socially subordinate female common marmosets (Callithrix jacchus) have markedly
      lower plasma cortisol levels than dominant females. Subordinate females also
      undergo hypoestrogenemic anovulation, and estrogen can elevate glucocorticoid
      levels. Therefore, we previously hypothesized that this cortisol difference is
      mediated by rank-related differences in reproductive hormones, probably
      estradiol. To test this possibility, we characterized the effects of the ovarian
      cycle and ovariectomy on plasma cortisol concentrations. Beginning in the early
      follicular phase, basal blood samples were collected from seven cycling female
      marmosets daily for 16 days and at 2- to 3-day intervals for another 16 days.
      Samples were collected identically from seven anovulatory subordinate females and
      seven long-term ovariectomized females. Cortisol levels changed reliably across
      the ovarian cycle, with levels in the mid- to late follicular, peri-ovulatory,
      and early luteal phases higher than those in the remainder of the cycle. Cortisol
      levels of cycling females were significantly higher than those of subordinates at
      all parts of the cycle, but were significantly higher than those of
      ovariectomized females only during the midcycle elevation. Unexpectedly,
      subordinates had significantly lower cortisol levels than ovariectomized females,
      as well as higher estradiol and estrone levels and lower progesterone and
      luteinizing hormone (LH) levels. These results confirm that circulating cortisol
      concentrations are modulated by reproductive function in female marmosets but
      also indicate that low cortisol levels in subordinate females cannot be
      attributed simply to hypoestrogenemia. Instead, other factors, such as direct
      effects of social subordination or suppression of LH levels, contribute to
      suppression of cortisol in subordinates.

PMID- 9571015
TI  - Society for Behavioral Neuroendocrinology Second Annual Meeting
AB  - Copyright

PMID- 9571016
TI  - Frank A. Beach Award
AB  - Copyright

PMID- 9571017
TI  - The origin of the alpha-domain intermediate in the folding of hen lysozyme.
AB  - Stopped-flow fluorescence and circular dichroism spectroscopy have been used in
      conjunction with quenched-flow hydrogen exchange labelling, monitored by
      electrospray ionization mass spectrometry, to compare the refolding kinetics of
      hen egg-white lysozyme at 20 degrees C and 50 degrees C. At 50 degrees C there is
      clear evidence for distinct fast and slow refolding populations, as observed at
      20 degrees C, although folding occurs significantly more rapidly. The folding
      process is, however, substantially more cooperative at the higher temperature. In
      particular, the transient intermediate on the major refolding pathway at 20
      degrees C, having persistent native-like structure in the alpha-helical domain of
      the protein, is not detected by hydrogen exchange labelling at 50 degrees C. In
      addition, the characteristic maximum in negative ellipticity and the minimum in
      fluorescence intensity observed in far UV CD and intrinsic fluorescence
      experiments at 20 degrees C, respectively, are not seen at 50 degrees C. Addition
      of 2 M NaCl to the refolding buffer at 50 degrees C, however, regenerates both
      the hydrogen exchange and optical properties associated with the alpha-domain
      intermediate but has no significant effect on the overall refolding kinetics.
      Together with previous findings, these results indicate that non-native
      interactions within the alpha-domain intermediate are directly responsible for
      the unusual optical properties observed during refolding, and that this
      intermediate accumulates as a consequence of its intrinsic stability in a folding
      process where the formation of stable structure in the beta-domain constitutes
      the rate-limiting step for the majority of molecules.

PMID- 9571018
TI  - Tertiary structure formation in the propeptide of subtilisin BPN' by successive
      amino acid replacements and its close relation to function.
AB  - The propeptide of subtilisin BPN', located between a signal peptide and the
      mature region of the protease, is known to exhibit inhibitory activity toward
      subtilisin BPN', in addition to its activity as an intramolecular chaperone that
      facilitates folding of subtilisin BPN'. Another unique feature is that although
      the isolated propeptide is in a random-coil state, it forms a defined tertiary
      structure when it is bound to subtilisin BPN'. In this study, amino acid
      replacements likely to increase the hydrophobicity of the propeptide have been
      introduced so that the isolated propeptide forms a defined tertiary structure. By
      successive replacements of Ala47 by Phe, Gly13 by Ile and Val65 by Ile, the
      propeptide was found to form a tertiary structure in addition to an increase in
      its secondary structure content, which were identified by circular dichoism
      spectra measurements. Concurrently, the propeptide, which is a temporary
      inhibitor in its wild-type form, became resistant to proteolytic digestion by
      subtilisin BPN'. These results show not only the close relationship between
      tertiary structure formation in the propeptide and its function as a protease
      inhibitor but also the ability of a random-coil protein to form a tertiary
      structure after a limited number of well-designed amino acid replacements.

PMID- 9571019
TI  - Contributions of the TATA box sequence to rate-limiting steps in transcription
      initiation by RNA polymerase II.
AB  - We have examined the role of the TATA box in determining transcription initiation
      frequency in vitro by studying a collection of promoters containing different
      TATA sequences in the context of the adenovirus major late promoter. In addition
      to measuring transcription rates, we have determined how the sequence changes
      affected the association and dissociation kinetics and the affinity of TBP
      binding. We observed that transcription from promoters containing the highest
      affinity TATA boxes is limited by the rate with which TBP associates with the
      promoter. In contrast, transcription from promoters containing lower affinity
      TATA boxes appears to be limited both by how much TBP is bound and by the
      relatively low occupancy of the conformation that can undergo subsequent steps in
      preinitiation complex assembly. The implications of these results in
      understanding the mechanism of transcription enhancement by transcriptional
      activators is discussed.

PMID- 9571020
TI  - Three-dimensional structure of bovine NADH:ubiquinone oxidoreductase (complex I)
      at 22 A in ice.
AB  - NADH:ubiquinone oxidoreductase (complex I) is the first and largest complex in
      the electron transport chain of mitochondria. The bovine complex purified from
      cardiac muscle consists of at least 42 different subunits with a combined
      molecular mass of about 890 kDa. The three-dimensional structure of the complex
      was determined at 22 A from single particles embedded in vitrified ice using
      electron cryo-microscopy. The structure was calculated using a new program to
      align particles, to correct for the contrast transfer function of the microscope,
      and to carry out the three-dimensional reconstruction of the complex. The bovine
      complex has the overall L-shaped appearance found in earlier studies of the
      closely related complex I from Neurospora crassa, but it differs by having a thin
      stalk region linking the membrane-bound globular arm with the intrinsic membrane
      domain. Thus, the stalk which measures about 30 A in diameter is likely to
      contain part of the electron transfer pathway linking the NADH binding site in
      the globular arm with the ubiquinone binding site in the membrane domain. The
      globular domain of bovine complex I is significantly bigger than that of the N.
      crassa enzyme, suggesting that the apparent additional subunit complexity of the
      bovine enzyme is associated with the globular part.

PMID- 9571021
TI  - Witnessing the evolution of transcription in mitochondria: the mitochondrial
      genome of the primitive brown alga Pylaiella littoralis (L.) Kjellm. Encodes a T7
      like RNA polymerase.
AB  - A region of the mitochondrial genome of the primitive brown alga Pylaiella
      littoralis containing a plasmid-like insert which contains a transcribed T7-phage
      type RNA polymerase gene is described. This is a first report of a phage-type RNA
      polymerase gene integrated in a mitochondrial genome. As the mitochondrial genome
      of this alga also contains sigma-70 proteobacterial promoter regions, i.e. traces
      of the ancestral alpha2betabeta'sigma-70 proteobacterial RNA polymerase, this
      genome witnesses two types of RNA polymerases. As such the mitochondrial genome
      of P. littoralis represents a unique stage in the evolution of transcription in
      mitochondria, which contrasts with that of the primitive protist Reclinomonas
      americana, which still retains the ancestral alpha2betabeta'sigma-70
      proteobacterial RNA polymerase genes, and with animals, land plants and fungi,
      which use phage-type polymerases.

PMID- 9571022
TI  - Recognition of core binding sites by bacteriophage integrases.
AB  - Bacteriophage integrases promote recombination between DNA molecules that carry
      attachment sites. They are members of a large and widely distributed family of
      site-specific recombinases with diverse biological roles. The integrases of
      phages lambda and HK022 are closely related members of this family, but neither
      protein efficiently recombines the attachment sites of the other phage. The
      nucleotides responsible for this specificity difference are located close to the
      points of recombinational strand exchange, within an integrase binding motif
      called the extended core binding site. There are four imperfectly repeated copies
      of this motif in each set of phage attachment sites, but only two, B' and C,
      contain major specificity determinants. When these specificity determinants were
      replaced by the corresponding nucleotides from a site with the alternative
      specificity, the resulting mutant was recombined by both integrases. Thus, the
      determinants act by impeding recombination promoted by the non-cognate integrase.
      We found that identical nucleotide substitutions within different core site
      copies had different effects on recombination, suggesting that integrase does not
      recognize each of the extended core binding sites in the same way. Finally,
      substitution at several positions in lambda integrase with the corresponding
      HK022-specific amino acids prevents recombination of lambda attachment sites, and
      this defect can be suppressed in an allele-specific manner by appropriate
      substitutions of HK022-specific nucleotides in the extended core binding sites.

PMID- 9571023
TI  - Direct versus indirect readout in the interaction of the trp repressor with non
      canonical binding sites.
AB  - Both direct and indirect readouts are utilized when the trp repressor binds to
      its operators. Here, we use gel-electrophoretic methods to examine the role
      played by direct and indirect readouts in the interaction of the repressor with a
      non-canonical binding site, similar to the mtr operator, and named trpGG. The
      stability and affinity of the 1:1 complexes of the trp repressor with this non
      canonical site are lower than those of the 1:1 complexes formed with either the
      natural consensus sequence or a consensus sequence found in a selection
      experiment. We attribute this to the inability of the trpGG target to make the
      same number of water-mediated hydrogen bonds as canonical trp binding sites. On
      the other hand, the 2:1 complex of the repressor with trpGG has high stability
      and affinity, similar to that of the 2:1 complex with a consensus sequence found
      by a selection experiment. The bend angle induced on the trpGG target by the
      binding of one repressor molecule is 27 degrees, which is similar to that
      measured in other 1:1 complexes with the repressor. The angle for the 2:1 complex
      is significantly larger (43 degrees versus 30 degrees in other 2:1 complexes). We
      present evidence suggesting that the deleterious effect of the sequence
      substitution in trpGG is compensated by the increased bend angle in the 2:1
      complex. These observations demonstrate that indirect readout may complement for
      direct readout in determining the nature of the interaction between trp repressor
      and its binding sites.

PMID- 9571024
TI  - The muscle thin filament as a classical cooperative/allosteric regulatory system.
AB  - It is generally accepted that the regulation of muscle contraction involves
      cooperative and allosteric interactions among the protein components, actin,
      myosin, tropomyosin and troponin. But, as yet, the individual role of each
      component has not been clearly identified. Here we compare the properties of the
      components of the muscle regulatory system with the corresponding components of
      two systems, hemoglobin and aspartate transcarbamylase, that are well described
      by the classical Monod, Wyman and Changeux (MWC) model. The analogy indicates
      that actin is the catalytic subunit, tropomyosin is the regulatory subunit and
      troponin in the absence and presence of Ca2+ is the allosteric inhibitor and
      activator, respectively. The analogy additionally indicates that the substrate is
      myosin-ATP (or myosin-ADP-Pi) rather than ATP. Also, in contrast to other MWC
      systems, the activating ligand for actin-tropomyosin is a myosin-nucleotide
      intermediate or product that binds tightly to actin, rather than the substrate
      which binds weakly. This tightly bound intermediate switches the system from the
      off-state to the on-state (T to R-state in MWC nomenclature) in a concerted
      transition, affecting n actin subunits, allowing force to be developed.

PMID- 9571025
TI  - Folding of beta-sheet membrane proteins: a hydrophobic hexapeptide model.
AB  - Beta-sheets, in the form of the beta-barrel folding motif, are found in several
      constitutive membrane proteins (porins) and in several microbial toxins that
      assemble on membranes to form oligomeric transmembrane channels. We report here a
      first step towards understanding the principles of beta-sheet formation in
      membranes. In particular, we describe the properties of a simple hydrophobic
      hexapeptide, acetyl-Trp-Leu5 (AcWL5), that assembles cooperatively into beta
      sheet aggregates upon partitioning into lipid bilayer membranes from the aqueous
      phase where the peptide is strictly monomeric and random coil. The aggregates,
      containing 10 to 20 monomers, undergo a relatively sharp and reversible thermal
      unfolding at approximately 60 degreesC. No pores are formed by the aggregates,
      but they do induce graded leakage of vesicle contents at very high peptide to
      lipid ratios. Because beta-sheet structure is not observed when the peptide is
      dissolved in n-octanol, trifluoroethanol or sodium dodecyl sulfate micelles,
      aggregation into beta-sheets appears to be an exclusive property of the peptide
      in the bilayer membrane interface. This is an expected consequence of the
      hypothesis that a reduction in the free energy of partitioning of peptide bonds
      caused by hydrogen bonding drives secondary structure formation in membrane
      interfaces. But, other features of interfacial partitioning, such as side-chain
      interactions and reduction of dimensionality, must also contribute. We estimate
      from our partitioning data that the free energy reduction per residue for
      aggregation is about 0.5 kcal mol-1. Although modest, its aggregate effect on the
      free energy of assembling beta-sheet proteins can be huge. This surprising
      finding, that a simple hydrophobic hexapeptide readily assembles into oligomeric
      beta-sheets in membranes, reveals the potent ability of membranes to promote
      secondary structure in peptides, and shows that the formation of beta-sheets in
      membranes is more facile than expected. Furthermore, it provides a basis for
      understanding the observation that membranes promote self-association of beta
      amyloid peptides. AcWL5 and related peptides thus provide a good starting point
      for designing peptide models for exploring the principles of beta-sheet formation
      in membranes.

PMID- 9571026
TI  - Structural and functional analysis of the 1:1 growth hormone:receptor complex
      reveals the molecular basis for receptor affinity.
AB  - The designed G120R mutant of human growth hormone (hGH) is an antagonist and can
      bind only one molecule of the growth hormone receptor. We have determined the
      crystal structure of the 1:1 complex between this mutant and the receptor
      extracellular domain (hGHbp) at 2.6 A resolution, and used it to guide a detailed
      survey of the structural and functional basis for hormone-receptor recognition.
      The overall structure of the complex is very similar to the equivalent portion of
      the 1:2 complex, showing that formation of the active complex does not involve
      major conformational changes. However, a segment involved in receptor-receptor
      interactions in the 1:2 complex is disordered in this structure, suggesting that
      its productive conformation is stabilized by receptor dimerization. The hormone
      binding site of the receptor comprises a central hydrophobic patch dominated by
      Trp104 and Trp169, surrounded by a hydrophilic periphery containing several well
      ordered water molecules. Previous alanine scanning showed that the hydrophobic
      "hot spot" confers most of the binding energy. The new structural data, coupled
      with binding and kinetic analysis of further mutants, indicate that the hot spot
      is assembled cooperatively and that many residues contribute indirectly to
      binding. Several hydrophobic residues serve to orient the key tryptophan
      residues; kinetic analysis suggests that Pro106 locks the Trp104 main-chain into
      a required conformation. The electrostatic contacts of Arg43 to hGH are less
      important than the intramolecular packing of its alkyl chain with Trp169. The
      true functional epitope that directly contributes binding energy may therefore
      comprise as few as six side-chains, participating mostly in alkyl-aromatic
      stacking interactions. Outside the functional epitope, multiple mutation of
      residues to alanine resulted in non-additive increases in affinity: up to tenfold
      for a hepta-alanine mutant. Contacts in the epitope periphery can therefore
      attenuate the affinity of the central hot spot, perhaps reflecting a role in
      conferring specificity to the interaction.

PMID- 9571027
TI  - A role for CH...O interactions in protein-DNA recognition.
AB  - The concept of CH...O hydrogen bonds has recently gained much interest, with a
      number of reports indicating the significance of these non-classical hydrogen
      bonds in stabilizing nucleic acid and protein structures. Here, we analyze the
      CH...O interactions in the protein-DNA interface, based on 43 crystal structures
      of protein-DNA complexes. Surprisingly, we find that the number of close
      intermolecular CH...O contacts involving the thymine methyl group and position C5
      of cytosine is comparable to the number of protein-DNA hydrogen bonds involving
      nitrogen and oxygen atoms as donors and acceptors. A comprehensive analysis of
      the geometries of these close contacts shows that they are similar to other
      CH...O interactions found in proteins and small molecules, as well as to
      classical NH...O hydrogen bonds. Thus, we suggest that C5 of cytosine and C5-Met
      of thymine form relatively weak CH...O hydrogen bonds with Asp, Asn, Glu, Gln,
      Ser, and Thr, contributing to the specificity of recognition. Including these
      interactions, in addition to the classical protein-DNA hydrogen bonds, enables
      the extraction of simple structural principles for amino acid-base recognition
      consistent with electrostatic considerations.

PMID- 9571028
TI  - Assessing protein structures with a non-local atomic interaction energy.
AB  - We describe a new approach, based on the energy of non-local interactions, to
      assess protein structures. The method uses a very sensitive and accurate atomic
      mean force potential (AMFP) to calculate the non-local energy profile (NL
      profile) of a proteins structure. Several protein models, built using the
      comparative modeling technique and containing several errors, were evaluated.
      These models exhibit a good stereochemistry and have been previously checked with
      different, widely used, methods that failed to detect the errors. The AMFP
      derived energy profiles are able to correlate high scores with point errors and
      misalignments in the models. The point errors are frequently found in loops or
      regions of structural differences between the template and the target protein.
      The misalignments are clearly detected with very high scores. The performance of
      the method was also tested for the assessment of X-ray solved protein structures.
      In a data set of 143 well solved and non-redundant protein structures, we find
      that the average energy Z-scores, obtained from AMFP, increase as the resolution
      decreases. In the case of structures that have already been described as having
      an unusual stereochemistry, very high Z-scores are obtained. Moreover, energy
      calculations for some pairs of obsolete and replacement proteins always show
      higher Z-scores for the obsolete proteins. Finally, two particular cases show the
      usefulness of the profiles in the assessment of X-ray solved protein structures.
      First, the NL-profile of a protein structure refined in the incorrect space group
      has very high scores in several regions. One region has already been described to
      be out-of-register with the density map of the structure. The NL-profile of the
      re-refined structure with the correct space group is vastly improved. In the
      second case, the method is able to accurately point out disordered residues, even
      if the atoms of these residues do not violate the sum of the van der Waals radii.
      ANOLEA, the program used to calculate the NL-profile of a protein structure
      containing one or more chains is accessible through the World Wide Web at:
      http://www.fundp.ac.be/pub/ANOLEA.html.

PMID- 9571029
TI  - Sedimentation and electrophoretic migration of DNA knots and catenanes.
AB  - Various site-specific recombination enzymes produce different types of knots or
      catenanes while acting on circular DNA in vitro and in vivo. By analysing the
      types of knots or links produced, it is possible to reconstruct the order of
      events during the reaction and to deduce the molecular "architecture" of the
      complexes that different enzymes form with DNA. Until recently it was necessary
      to use laborious electron microscopy methods to identify the types of knots or
      catenanes that migrate in different bands on the agarose gels used to analyse the
      products of the reaction. We reported recently that electrophoretic migration of
      different knots and catenanes formed on the same size DNA molecules is simply
      related to the average crossing number of the ideal representations of the
      corresponding knots and catenanes. Here we explain this relation by demonstrating
      that the expected sedimentation coefficient of randomly fluctuating knotted or
      catenated DNA molecules in solution shows approximately linear correlation with
      the average crossing number of ideal configurations of the corresponding knots or
      catenanes.

PMID- 9571030
TI  - Crystal structure of Leishmania mexicana glycosomal glyceraldehyde-3-phosphate
      dehydrogenase in a new crystal form confirms the putative physiological active
      site structure.
AB  - The structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from
      the trypanosomatid parasite Leishmania mexicana in a new crystal form has been
      determined by X-ray crystallography. The protein crystallizes in space group P21
      with one 156 kDa tetramer per asymmetric unit. The model of the protein with
      bound NAD+s and phosphates has been refined against 81% complete data from 10.0
      to 2. 8 A to a crystallographic Rfactor of 0.217. The present structure confirms
      two key aspects of the previously reported orthorhombic crystal structure of L.
      mexicana GAPDH (LmGAPDH): the unusual conformation of a loop in the active site,
      and the repositioning of the inorganic phosphate binding site compared with
      crystal structures of GAPDHs from other organisms. As the monoclinic crystals of
      LmGAPDH were grown at a phosphate concentration and pH that were even closer to
      physiological conditions than were the orthorhombic LmGAPDH crystals, the present
      structure reinforces the physiological relevance of the active site structure
      seen in the previous orthorhombic crystal of LmGAPDH.

PMID- 9571031
TI  - Human immunodeficiency virus type 1 Vpr localization: nuclear transport of a
      viral protein modulated by a putative amphipathic helical structure and its
      relevance to biological activity.
AB  - Protein import into the nucleus is generally considered to involve specific
      nuclear localization signals (NLS) though it is becoming increasingly clear that
      efficient and well controlled import of proteins which lack a canonical NLS also
      occurs in cells. Human immunodeficiency virus type 1 (HIV-1) Vpr is one such
      protein which does not have an identifiable canonical NLS and yet efficiently
      localizes to the nuclear compartment. Here, we use confocal microscopy to
      demonstrate that mutations in the putative central hydrophobic helix of Vpr
      result in the retention of the protein in highly localized ring-like structures
      around the nuclear periphery with striking impairment in their ability to enter
      the nuclear interior. By characterizing other biological activities associated
      with this protein, such as its ability to incorporate into budding virions and
      its ability to arrest cells in G2, we show that this helical domain is specific
      for the nuclear translocation of the protein with very little effect on these
      other functions. Interestingly, however, perturbation of this helical motif also
      perturbs the protein's ability to augment viral replication in primary human
      macrophages indicating that the integrity of this secondary structure is
      essential for optimal infection in these non-dividing cells.

PMID- 9571033
TI  - The mechanism of the elongation and branching reaction of poly(ADP-ribose)
      polymerase as derived from crystal structures and mutagenesis.
AB  - The binding site for the acceptor substrate poly(ADP-ribose) in the elongation
      reaction of the ADP-ribosyl transferase poly(ADP-ribose) polymerase (PARP) was
      detected by cocrystallizing the enzyme with an NAD+ analogue. The site was
      confirmed by mutagenesis studies. In conjunction with the binding site of the
      donor NAD+, the bound acceptor reveals the geometry of the elongation reaction.
      It shows in particular that the strictly conserved glutamate residue of all ADP
      ribosylating enzymes (Glu988 of PARP) facilitates the reaction by polarizing
      both, donor and acceptor. Moreover, the binding properties of the acceptor site
      suggest a mechanism for the branching reaction, that also explains the dual
      specificity of this transferase for elongation and branching, which is unique
      among polymer-forming enzymes.

PMID- 9571032
TI  - Interactions of the antiviral quinoxaline derivative 9-OH-B220 [2, 3-dimethyl-6
      (dimethylaminoethyl)- 9-hydroxy-6H-indolo-[2, 3-b]quinoxaline] with duplex and
      triplex forms of synthetic DNA and RNA.
AB  - The binding of an antiviral quinoxaline derivative, 2,3-dimethyl- 6 -
      (dimethylaminoethyl) - 9 - hydroxy - 6H - indolo - [2,3 - b]quinoxaline (9-OH
      B220), to synthetic double and triple helical DNA (poly(dA).poly(dT) and
      poly(dA).2poly(dT)) and RNA (poly(rA). poly(rU) and poly (rA).2poly(rU)) has been
      characterized using flow linear dichroism (LD), circular dichroism (CD),
      fluorescence spectroscopy, and thermal denaturation. When either of the DNA
      structures or the RNA duplex serve as host polymers a strongly negative LD is
      displayed, consistent with intercalation of the chromophoric ring system between
      the base-pairs/triplets of the nucleic acid structures. Evidence for this
      geometry also includes weak induced CD signals and strong increments of the
      fluorescence emission intensities upon binding of the drug to each of these
      polymer structures. In agreement with intercalative binding, 9-OH-B220 is found
      to effectively enhance the thermal stability of both the double and triple
      helical states of DNA as well as the RNA duplex. In the case of
      poly(dA).2poly(dT), the drug provides an unusually large stabilization of its
      triple helical state; upon binding of 9-OH-B220 the triplex-to-duplex equilibrium
      is shifted towards higher temperature by 52.5 deg. C in a 10 mM sodium cacodylate
      buffer (pH 7.0) containing 100 mM NaCl and 1 mM EDTA. When triplex RNA serves as
      host structure, LD indicates that the average orientation angle between the drug
      chromophore plane and the helix axis of the triple helical RNA is only about 60
      to 65 degrees. Moreover, the thermal stabilizing capability, as well as the
      fluorescence increment, CD inducing power and perturbations of the absorption
      envelope, of 9-OH-B220 in complex with the RNA triplex are all less pronounced
      than those observed for the complexes with DNA and duplex RNA. These features
      indicate binding of 9-OH-B220 in the wide and shallow minor groove of
      poly(rA).2poly(rU). Based on the present results, some implications for the
      applications of this low-toxic, antiviral and easily administered drug in an
      antigene strategy, as well as its potential use as an antiretroviral agent, are
      discussed.

PMID- 9571034
TI  - The role of the 3' external transcribed spacer in yeast pre-rRNA processing.
AB  - We have undertaken a deletion analysis of the 3' external transcribed spacer (3'
      ETS) in the pre-rRNA of Saccharomyces cerevisiae. A stem loop structure
      immediately 3' to the 25 S rRNA region is necessary and sufficient for processing
      of the 3' ETS. This is believed to be by cotranscriptional cleavage by Rnt1p, the
      yeast homologue of RNase III. In addition, this stem-loop is required for
      cleavage of site A3 by RNase MRP and for processing at site B1L, in the 3' region
      of ITS1. Processing at an upstream site in ITS1, site A2, and at sites in the 5'
      external transcribed spacer are not affected, even by complete deletion of the 3'
      ETS. We conclude that processing in the 3' ETS and in ITS1 is coupled. This would
      constitute a quality control that prevents synthesis of the 5. 8 S rRNA and 5'
      end maturation of the 25 S rRNA in transcripts which are incomplete due to
      premature transcription termination.

PMID- 9571035
TI  - TRF1 promotes parallel pairing of telomeric tracts in vitro.
AB  - Human telomeres consist of long arrays of TTAGGG repeats bound to the telomere
      specific proteins, TRF1 and TRF2. Here we describe the structure of in vitro
      complexes formed between telomeric DNA and TRF1 as deduced by electron
      microscopy. Visualization of TRF1 bound to DNA containing six or 12 tandem TTAGGG
      repeats revealed a population of DNAs containing a spherical protein complex
      localized just to the repeats. Mass analysis of the protein complexes suggested
      binding of TRF1 dimers and tetramers to the TTAGGG repeats. The DNA was not
      significantly compacted or extended by protein binding. TRF1 formed filamentous
      structures on longer telomeric repeat arrays (>/=27 repeats) consistent with the
      presence of an array of bound TRF1 dimers. Unexpectedly, there was a strong
      propensity for two telomeric tracts to form paired synapses over the TRF1 covered
      segment. Up to 30% of the TRF1-bound DNAs could be found in a paired
      configuration with a strong bias for a parallel as contrasted to an antiparallel
      arrangement. TRF1-induced pairing was confirmed using a ligation assay which
      detected the formation of DNA multimers dependent on the presence of TRF1 and a
      27mer repeat array in the DNA. These findings suggests that this protein may have
      an architectural role at telomeres. We discuss the possibility that TRF1
      dependent changes in the conformation of telomeres are involved in the regulation
      of telomere length.

PMID- 9571036
TI  - Functions of the ATP hydrolysis subunits (RecB and RecD) in the nuclease
      reactions catalyzed by the RecBCD enzyme from Escherichia coli.
AB  - The RecBCD enzyme from Escherichia coli is an ATP-dependent nuclease and
      helicase. Two of its subunits, the RecB and RecD proteins, are DNA-dependent
      ATPases. We have purified RecB and RecD proteins with mutations in their
      consensus ATP binding sites to study the functions of these subunits in the ATP
      dependent nuclease activities of RecBCD. Reconstituted heterotrimeric enzymes
      were prepared by mixing wild-type RecB or RecB-K29Q mutant protein (RecB*) with
      purified RecC protein, and with a histidine-tagged wild-type RecD (hD) or mutant
      hRecD-K177Q (hD*) protein. RecBCD and all four reconstituted enzymes (wild-type,
      two single mutants, and the double mutant) cleave a single-stranded DNA oligomer
      substrate (25-mer) in the absence of ATP at rates of 0.03 to 0.06 min-1. The
      nuclease reaction catalyzed by RecB*ChD* is not stimulated significantly by ATP,
      while the reactions catalyzed by RecBCD, RecBChD, RecBChD*, and RecB*ChD are 300
      to 3000 fold faster in the presence of 0.5 mM ATP. RecB*ChD* also has very low
      ATP hydrolysis activity (approximately 10(3)-fold less than RecBCD), as do the
      individual mutant RecB* and hRecD* proteins (approximately 100-fold less than
      RecB or hRecD). The products from the ATP-stimulated nuclease reaction with the
      oligomer substrate suggest a mechanism where two DNA molecules bind to the enzyme
      in opposite orientations and are cleaved by the nuclease active site. Cleavage
      towards the 3'-end of one oligomer (observed with RecBChD*) depends on the wild
      type RecB subunit, while RecD-dependent cleavage (observed with RecB*ChD) occurs
      towards the 5'-end of the second bound oligomer.

PMID- 9571037
TI  - Structural similarities between Escherichia coli RuvA protein and other DNA
      binding proteins and a mutational analysis of its binding to the holliday
      junction.
AB  - Comparison of the structure of Escherichia coli RuvA with other proteins in the
      Protein Data Bank gives insights into the probable modes of association of RuvA
      with the Holliday junction during homologous recombination. All three domains of
      the RuvA protein possess striking structural similarities to other DNA-binding
      proteins. Additionally, the second domain of RuvA contains two copies of the
      helix-hairpin-helix (HhH) structural motif, which has been implicated in non
      sequence-specific DNA binding. The two copies of the motif are related by
      approximate 2-fold symmetry and may form a bidentate DNA-binding module. The
      results described provide support for the organization of the arms of the DNA in
      our RuvA/Holliday junction complex model and support the involvement of the HhH
      motifs in DNA binding.

PMID- 9571038
TI  - Structural recognition and distortion by the DNA junction-resolving enzyme RusA.
AB  - RusA is a relatively small DNA junction-resolving enzyme of lambdoid phage
      origin. Many of the physical characteristics of this enzyme are similar to those
      of junction-resolving enzymes of different origins. RusA binds to DNA junctions
      as a dimer, with a dissociation constant of 2 to 7 nM. RusA also exists in
      dimeric form in free solution, with a half time for subunit exchange of 4.2
      minutes. We find that RusA can cleave both fixed junctions and those that can
      undergo a number of steps of branch migration, and confirm that the enzyme
      exhibits a strong preference for cleavage 5' to a CpC sequence. We have isolated
      a mutant protein, RusA D70N, that is completely inactive in cleavage while
      binding normally to DNA junctions, suggesting a role for aspartate 70 in the
      cleavage reaction. Constraining the conformation of the junction by means of
      tethering the helical ends leads to a marked reduction in cleavage rate by RusA,
      suggesting that the structure must be altered for cleavage. Using comparative gel
      electrophoresis we find that the global structure of the DNA junction is altered
      on RusA binding, into a structure that is different from any that is formed by
      the free junction. Moreover, the structure of the complex is the same
      irrespective of the presence or absence of magnesium ions. Thus, like all the
      junction-resolving enzymes, RusA both recognises and distorts the structure of
      DNA junctions.

PMID- 9571039
TI  - Effect of accessory proteins on T4 DNA polymerase replication fidelity.
AB  - The influence of replication accessory proteins on the fidelity of T4 DNA
      polymerase has been examined. Steady-state kinetic measurements showed that
      exonuclease-deficient T4 DNA polymerase, alone or with clamp loaders gp44/gp62
      and polymerase clamp gp45, displays decreased binding affinity for incorrect as
      compared to correct dNTPs and a deceased kcat for misinsertion as compared to
      correct insertion. Kinetic constants were similar with and without accessory
      proteins, indicating that accessory proteins had little effect on misinsertion.
      They also had little effect on the Km value for extension of a T.T mismatch.
      However, the kcat value for T.T mismatch extension was fivefold higher in the
      presence of the clamp loader and clamp proteins. Thus, in the absence of
      proofreading, these accessory proteins may promote stable misincorporation. The
      kinetic analysis is supported by error rate determinations during gap-filling
      synthesis, which require both misinsertion and mispair extension. For some
      mispairs, the accuracy of exonuclease-deficient polymerase alone is similar to
      that in the presence of clamp loader, clamp and single-stranded DNA binding
      protein (gp32). However, exonuclease-deficient holoenzyme complex is actually
      less accurate than the polymerase alone for some base substitutions. We suggest
      that gp45 promotes extension of mismatches by tethering the polymerase to DNA, a
      process that may be relevant to replication past lesions or other blocks to DNA
      synthesis. The error rate for one-nucleotide deletions in homopolymeric runs was
      similar for the polymerase with or without its accessory proteins. This implies
      that strand misalignment errors arise during highly processive replication. Thus,
      either unpaired bases can migrate through the run while the DNA polymerase is
      bound to the template-primer, or the DNA polymerase dissociates from the DNA to
      allow misalignment but remains tethered to the template through interactions with
      the clamp. Finally, the T4 replication accessory proteins reduced by >/=10-fold
      the rate at which exonuclease-deficient T4 DNA polymerase generated deletions of
      larger numbers of nucleotides, indicating that these proteins influence
      replication fidelity for other than single base mutations.

PMID- 9571040
TI  - How E. coli DNA polymerase I (Klenow fragment) distinguishes between deoxy- and
      dideoxynucleotides.
AB  - Deoxy- and dideoxynucleotides differ only in whether they have a hydroxyl
      substituent at C-3' of the ribose moiety, and yet the Klenow fragment DNA
      polymerase prefers the natural (dNTP) substrate by several thousandfold. We have
      used this preference in order to investigate how Klenow fragment interacts with
      the sugar portion of an incoming dNTP. We screened mutant derivatives of Klenow
      fragment so as to identify those amino acid residues that play important roles in
      distinguishing between dNTPs and ddNTPs. Substitution of Phe762 with Ala or Tyr
      caused a dramatic decrease in the discrimination against ddNTPs, while mutations
      in Tyr766 and Glu710 had a smaller effect, suggesting that these two side-chains
      play secondary roles in the selection of dNTPs over ddNTPs. In order to
      understand the interactions in the enzyme-DNA-dNTP ternary complex, pre-steady
      state kinetic parameters for the incorporation of dNTPs and ddNTPs were
      determined for wild-type Klenow fragment and for mutant derivatives that showed
      changes in dNTP/ddNTP discrimination. From elemental effect measurements we infer
      that selection against dideoxynucleotides takes place in the transition state for
      the conformational change that precedes phosphoryl transfer. The crucial role of
      the Phe762 side-chain appears to be to constrain the dNTP molecule so that the 3'
      OH can make an interaction with another group within the ternary complex. When
      Tyr is substituted at position 762, the same interactions can take place to
      position the dNTP, but specificity against the ddNTP is lost because the phenolic
      OH can compensate for the missing 3'-OH of the nucleotide. Substitution of the
      smaller Ala side-chain results in a loss in specificity because the dNTP is no
      longer appropriately constrained. Measurement of reaction rates as a function of
      magnesium ion concentration suggests that the interaction made with the dNTP 3'
      OH may involve a metal ion and the Glu710 side-chain, the simplest scenario being
      that both the 3'-OH and the carboxylate of Glu710 are ligands to the same metal
      ion.

PMID- 9571041
TI  - Identification of regulatory regions which confer muscle-specific gene
      expression.
AB  - For many newly sequenced genes, sequence analysis of the putative protein yields
      no clue on function. It would be beneficial to be able to identify in the genome
      the regulatory regions that confer temporal and spatial expression patterns for
      the uncharacterized genes. Additionally, it would be advantageous to identify
      regulatory regions within genes of known expression pattern without performing
      the costly and time consuming laboratory studies now required. To achieve these
      goals, the wealth of case studies performed over the past 15 years will have to
      be collected into predictive models of expression. Extensive studies of genes
      expressed in skeletal muscle have identified specific transcription factors which
      bind to regulatory elements to control gene expression. However, potential
      binding sites for these factors occur with sufficient frequency that it is rare
      for a gene to be found without one. Analysis of experimentally determined muscle
      regulatory sequences indicates that muscle expression requires multiple elements
      in close proximity. A model is generated with predictive capability for
      identifying these muscle-specific regulatory modules. Phylogenetic footprinting,
      the identification of sequences conserved between distantly related species,
      complements the statistical predictions. Through the use of logistic regression
      analysis, the model promises to be easily modified to take advantage of the
      elucidation of additional factors, cooperation rules, and spacing constraints.

PMID- 9571042
TI  - Phosphatidylinositol and inositol involvement in Alzheimer amyloid-beta fibril
      growth and arrest.
AB  - A key pathological feature of Alzheimer's disease is the formation and
      accumulation of amyloid fibres. The major component is the 39 to 42 residue
      amyloid-beta peptide (Abeta) which is an internal proteolytic fragment of the
      integral membrane amyloid precursor protein. Aggregation of Abeta into insoluble
      amyloid fibres is a nucleation-dependent event that may be modulated by the
      presence of amyloid-associated molecules. Fibril formation is also associated
      with neurotoxicity which may be the result of specific Abeta interactions with
      membrane proteins and/or lipids. Using circular dichroism spectroscopy, tyrosine
      fluorescence spectroscopy and electron microscopy, we have examined the binding
      of Abeta peptides 1-40 (Abeta40) and 1-42 (Abeta42) to the glycolipid,
      phosphatidylinositol (PI), and different inositol headgroups. At pH 6.0 and in
      the presence of PI vesicles, both Abeta40 and Abeta42 adopted an amyloidogenic
      beta-structure. In contrast, at neutral pH only Abeta42 folded into a beta
      structure in the presence of PI vesicles. To determine whether the induction of
      beta-structure stemmed from interactions with the headgroup of PI, the effects of
      inositol derivatives on Abeta were also examined. At pH 7.0, myo-inositol was
      sufficient to induce beta-structure in Abeta42 but had no effect on the
      conformation of Abeta40. Myo-inositol may promote beta-structure as a result of
      its ability to be both a hydrogen-bond donor and acceptor. Mono-, di- and
      triphosphorylated forms of inositol had reduced ability to induce beta-structure
      in both peptides. The results from this study indicate that interaction of
      Abeta40 and Abeta42 with PI acts as a seed for fibril formation while myo
      inositol stabilizes a soluble Abeta42 micelle.

PMID- 9571043
TI  - Surface located procollagen N-propeptides on dermatosparactic collagen fibrils
      are not cleaved by procollagen N-proteinase and do not inhibit binding of decorin
      to the fibril surface.
AB  - Dermatosparaxis is a recessive disorder of animals (including man) which is
      caused by mutations in the gene for the enzyme procollagen N-proteinase and is
      characterised by extreme skin fragility. Partial loss of enzyme activity results
      in accumulation of pNcollagen (collagen with N-propeptides) and abnormal collagen
      fibrils in the fragile skin. How the N-propeptides persist in the tissue and how
      abnormal fibril morphology results in fragile skin is poorly understood. Using
      biochemical and quantitative mass mapping electron microscopy we showed that the
      collagen fibrils in the skin of a dermatosparactic calf contained 57% type I
      pNcollagen and 43% type I collagen and the fibrils were irregularly arranged in
      bundles and hieroglyphic in cross-section. Image analysis of the fibril cross
      sections suggested that the deviation from circularity of dermatosparactic
      fibrils was caused by N-propeptides of pNcollagen being located at the fibril
      surface. Comparison of experimental and theoretical axial mass distributions of
      the fibrils showed that the N-propeptides were located to the overlap zone of the
      fibril D-period (where D=67 nm, the characteristic axial periodicity of collagen
      fibrils). Treatment of the dermatosparactic fibrils with N-proteinase did not
      remove the N-propeptides from the fibrils, although the N-propeptides were
      efficiently removed by trypsin and chymotrypsin. However, the N-propeptides were
      efficiently cleaved by the N-proteinase when the pNcollagen molecules were
      extracted from the fibrils. These results are consistent with close packing of N
      propeptides at the fibril surface which prevented cleavage by the N-proteinase.
      Long-range axial mass determination along the fibril length showed gross non
      uniformity with multiple mass bulges. Of note is the skin fragility in
      dermatosparaxis, and also the appearance of mass bulges along the fibril long
      axis symptomatic of the fragile skin of mice which lack decorin. Western blot
      analysis showed that the dermatosparactic fibrils bound elevated levels of the
      proteoglycan, compared with normal skin fibrils. The results showed that N
      propeptides can distort the morphology of fibrils, that they do not inhibit
      binding of gap-associated macromolecules (such as decorin) and that the normal
      mechanical properties of skin are strongly dependent on the close association of
      near-cylindrical fibrils, thereby enabling maximal fibril-fibril interactions.

PMID- 9571044
TI  - Molecular structure of a barley alpha-amylase-inhibitor complex: implications for
      starch binding and catalysis.
AB  - alpha-Amylases are widely occurring, multidomain proteins with a catalytic
      (beta/alpha)8-barrel. In barley alpha-amylase, insight into the catalytic
      mechanism is gained from the X-ray crystal structure of its molecular complex
      with acarbose, a pseudotetrasaccharide that acts like a transition-state analogue
      and which is shown to bind at two specific regions of the enzyme. The structure
      of the complex has been refined to an R-factor of 15.1% for all observations with
      Fo>sigma(Fo) between 10 and 2.8 A resolution. A difference Fourier map produced
      after refinement of the native structure against the data of the acarbose complex
      clearly revealed density corresponding to two oligosaccharide-binding sites. One
      of these is defined as the surface-located starch granule-binding site
      characteristic of cereal alpha-amylases. It involves stacking of two acarbose
      rings on Trp276 and Trp277. The other binding region is the active site covering
      subsites -1, +1 and +2. Here, Glu204 is positioned to act in general acid/base
      catalysis protonating the glucosidic oxygen atom assisted by Asp289. A water
      molecule that bridges Glu204 and Asp289 is found at the entrance cavity
      containing a total of five water molecules. This water molecule is proposed to
      reprotonate Glu204 and supply the hydroxyl ion for nucleophilic attack on the
      glucosyl C1 atom. Asp 179 acts as the nucleophile that can bind covalently to the
      substrate intermediate after bond cleavage. The present complex structure
      together with the conservation of active-site residues among alpha-amylases and
      related enzymes, are consistent with a common catalytic mechanism for this class
      of retaining carbohydrases.

PMID- 9571045
TI  - The structure of glutamine-binding protein complexed with glutamine at 1.94 A
      resolution: comparisons with other amino acid binding proteins.
AB  - The crystal structure of the glutamine-binding protein (GlnBP) complexed with its
      ligand (Gln) was determined and refined to 1.94 A resolution. This ellipsoidal
      protein has two globular domains and is approximately 52 Ax40 Ax35 A in size. The
      glutamine ligand is located in the cleft between the two domains and stablized by
      hydrogen bondings and ionic interactions with Asp10, Gly68, Thr70, Ala67, Asp157,
      Arg75, Lys115, Gly119 and His156. The aliphatic portion of the glutamine ligand
      is sandwiched in a hydrophobic pocket formed between Phe13 and Phe50 and has 21
      van der Waals contacts with GlnBP. Lys115 and His156, that are unique to GlnBP
      among amino acid binding proteins, apparently contribute to the ligand binding
      specificity of GlnBP. Asp10 is within 3 A of Lys115. These two residues are over
      10 A apart in the ligand-free form of the GlnBP. In addition, GlnBP-Gln exhibits
      a large-scale movement of the two hinges connecting the two globular domains upon
      ligand binding. The most significant changes are 41.1 degrees in the phi angle of
      Gly89 and 34.3 degrees in the psi angle of Glu181 from the first and the second
      hinge of the protein, respectively. Besides the original six hydrogen bonds,
      three extra hydrogen bonds can be observed between the two hinge strands upon
      ligand binding. A hydrogen bond network connects the large domain to the second
      hinge and a second hydrogen bond network coalesces the small domain to the same
      strand, both via interaction with the glutamine ligand. Although the two strands
      of the hinge connecting the domains do not directly participate in the ligand
      binding, Gln183 and Tyr185 from the second hinge may be involved in the cascade
      of the conformational change that is induced by ligand binding.

PMID- 9571046
TI  - Succinimide and isoaspartate residues in the crystal structures of hen egg-white
      lysozyme complexed with tri-N-acetylchitotriose.
AB  - The isomerization of Asp101 to isoaspartate autocatalytically proceeds via a
      succinimide intermediate in hen egg-white lysozyme at a mildly acidic condition.
      The crystal structures of succinimide and isoaspartate forms of the lysozyme
      proteins, each complexed with a tri-N-acetylchitotriose ligand, have been
      determined at 1.8 A resolution, and distinctively elucidate coplanar cyclic
      aminosuccinyl and beta-linked isoaspartyl residues. Compared with the liganded
      native protein with normal Asp101, succinimide 101 protrudes toward the ligand,
      and isoaspartate 101 extends away from the ligand. The formations of these
      residues caused the loss of three hydrogen-bonds between the ligand and the side
      chains of Asp101 and Asn103 along with 0.5 A displacement of the ligand location.

PMID- 9571047
TI  - The three-dimensional structure of an avian class-mu glutathione S-transferase,
      cGSTM1-1 at 1.94 A resolution.
AB  - Glutathione S-transferase cGSTM1-1, an avian class-mu enzyme with high sequence
      identity with rGSTM3-3, was expressed heterologously in Escherichia coli. The
      three-dimensional structure of this protein that co-crystallized with an
      inhibitor, S-hexylglutathione, was determined by the molecular replacement method
      and refined to 1.94 A resolution. The three-dimensional structure and the folding
      topology of the dimeric cGSTM1-1 closely resembles those of other class-mu GSTs.
      The bound inhibitor, S-hexylglutathione, orients in disparate directions in the
      two subunits. The combined space occupied by the hexyl moiety of the inhibitors
      overlaps with that reported for rGSTM1-1 co-crystallized with (9 S,10 S)-9-(S
      glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene. Conformational differences at
      a flexible loop (residue 35 to 40) were also observed between the crystal
      structures of cGSTM1-1 and rGSTM1-1.cGSTM1-1 has the highest epoxidase activity
      among all the class-mu enzymes reported. Tyr115, has been identified as a residue
      that participates in the epoxidase activity of class-mu glutathione S-transferase
      and is conserved in cGSTM1-1. The epoxidase and trans-4-phenyl-3-buten-2-one
      conjugating activity of cGSTM1-1 are decreased drastically but not abolished by
      replacing Tyr115 with phenylalanine. The specificity constant of the cGSTM1
      1(Y115F) mutant, with 1-chloro-2,4-dinitrobenzene as substrate, is 15-fold higher
      than that of the wild-type enzyme.

PMID- 9571048
TI  - Solution structure of the human Hck SH3 domain and identification of its ligand
      binding site.
AB  - SH3 domains are protein binding domains that occur widely among signal
      transduction proteins. Here, we present the NMR-determined solution structure of
      the SH3 domain from the cytoplasmic protein tyrosine kinase, Hck. Hck is involved
      in a number of cell signal transduction pathways, frequently in pathways
      associated with immune response. SH3 domains bind proteins via a left-handed
      polyproline type II helix on the target protein. We have assessed the structural
      impact of binding to a ligand through addition of a peptide corresponding to a
      proline-rich region of a Hck target, the GTPase activating protein of the Ras
      pathway. Ligand binding effects small structural changes and stabilizes the SH3
      domain structure. Also, we have compared the solution structure of the Hck SH3
      domain to the crystal structure of Hck, in which the SH3 domain exhibits an
      intramolecular binding to an interdomain linker region. These structures are
      interpreted as the apo- and holo- forms of the Hck SH3 domain.

PMID- 9571049
TI  - Asymmetry, commitment and inhibition in the GroE ATPase cycle impose alternating
      functions on the two GroEL rings.
AB  - The ATPase cycle of GroE chaperonins has been examined by transient kinetics to
      dissect partial reactions in complexes where GroEL is asymmetrically loaded with
      nucleotides. The occupation of one heptameric ring by ADP does not inhibit the
      loading of the other with ATP nor does it prevent the consequent structural
      rearrangement to the "open" state. However, ADP binding completely inhibits ATP
      hydrolysis in the asymmetric complex, i.e. ATP cannot by hydrolysed when ADP is
      bound to the other ring. This non-competitive inhibition of the ATPase by ADP is
      consistent with a ring-switching, or "two-stroke", mechanism of the type:
      ATP:GroEL --> ADP:GroEL --> ADP:GroEL:ATP --> GroEL:ATP --> GroEL:ADP, i.e. with
      respect to the GroEL rings, ATP turns over in an alternating fashion. When the
      ATP-stabilized, "open" state is challenged with hexokinase and glucose, to quench
      the free ATP, the open state relaxes slowly (0.44 s-1) back to the apo (or
      closed) conformation. This rate, however, is three times faster than the
      hydrolytic step, showing that bound ATP is not committed to hydrolysis. When
      GroES is bound to the GroEL:ATP complex and the system is quenched in the same
      way, approximately half of the bound ATP undergoes hydrolysis on the chaperonin
      complex showing that the co-protein increases the degree of commitment. Thus, non
      competitive inhibition of ATP hydrolysis, combined with the ability of the co
      protein to block ligand exchange between rings has the effect of imposing a
      reciprocating cycle of reactions with ATP hydrolysing, and GroES binding, on each
      of the GroEL rings in turn. Taken together, these data imply that the dominant,
      productive steady state reaction in vivo is: GroEL:ATP:GroES --> GroEL:ADP:GroES 
      -> ATP:GroEL:ADP:GroES --> ATP:GroEL:ADP --> GroES:ATP:GroEL:ADP -->
      GroES:ATP:GroEL for a hemi-cycle, and that significant inhibi tion of hydrolysis
      may arise through the formation of a dead-end ADP:GroEL:ATP:GroES complex.

PMID- 9571050
TI  - Position dependence of non-polar amino acid intrinsic helical propensities.
AB  - Until now and based on the success of the helix/coil transition theory it has
      been assumed that the alpha-helical propensities of the amino acids are position
      independent. This has been critical to derive the set of theoretical parameters
      for the 20 natural amino acids. Here, we have analyzed the behavior of several
      non-polar residues, Val, Ile, Leu, Met and Gly at the N-cap, at each position of
      the first helical turn and at a central helical position of a 16-residue peptide
      model system that starts with eight consecutive alanine residues. We have
      interpreted the results from these experiments with the model of the helix/coil
      transition (AGADIR), that indicates that the intrinsic helical propensity is
      position dependent. Gly, Val and Ile are more favorable at the first turn than in
      the middle of the alpha-helix, while for Leu and Met we observe the opposite
      behavior. The differences between the observed helical propensities are as large
      as 1.0 kcal/mol in some cases. Molecular modeling calculations using the ECEPP/2
      force-field equipped with a hydration potential show that this effect can be
      explained by the combination of three factors: (a) the side-chains in the first
      helix turn are more solvent-exposed; (b) they have fewer intramolecular van der
      Waals' contacts; and (c) they posses higher configurational entropy than that in
      the central position of an alpha-helix. The position-dependent results of the
      calculations are in reasonable agreement with the experimental estimates and with
      the intrinsic propensities of the amino acids derived from the statistical
      analysis of the protein structure database.

PMID- 9571051
TI  - Structural changes in the region directly adjacent to the DNA-binding helix
      highlight a possible mechanism to explain the observed changes in the sequence
      specific binding of winged helix proteins.
AB  - The hepatocyte nuclear factor 3 (HNF-3)/fork head (fkh) family contains a large
      number of transcription factors and folds into a winged helix motif. Despite
      having almost invariable amino acid sequences in their principal DNA-binding
      helices, HNF-3/fkh proteins show a wide diversity of sequence-specific binding.
      Previous studies of chimeric HNF-3/fkh proteins demonstrated that the binding
      specificity is primarily influenced by a region directly adjacent to the binding
      helix. We report our findings of an NMR structural study performed on an HNF
      3/fkh family member (Genesis, formerly HFH-2) and compare it to that of another
      family member (HNF-3gamma) complexed to DNA and determined by X-ray
      crystallography. It is found that in comparison to HNF-3gamma, Genesis contains
      an extra small helix directly prior to the N terminus of the primary DNA contact
      helix. Due to the insertion of this helix, a shorter and slightly re-positioned
      primary DNA contact helix is observed, which we believe leads to the DNA-binding
      specificity differences among family members.

PMID- 9571052
TI  - Ligand-induced domain movement in an antibody Fab: molecular dynamics studies
      confirm the unique domain movement observed experimentally for Fab NC6.8 upon
      complexation and reveal its segmental flexibility.
AB  - Two molecular dynamics simulations were carried out for the antibody Fab NC6.8,
      both with and without the guanidinium sweetener ligand NC174, in order to assess
      the segmental flexibility as well as the conformational changes upon ligand
      binding. Trajectory analyses of the simulation of the uncomplexed Fab suggest low
      amplitude motions of the Ig domains with respect to each other, most clearly
      reflected by a periodic alteration of the elbow angle within a range of 11
      degrees. Upon insertion of the hapten into the binding site, the quaternary
      structure of the Fab exhibits considerable rearrangements: the elbow angle
      changes by almost 30 degrees, the light chain is elongated and the heavy chain
      becomes more flexed. Comparison with experiment reveals some interesting
      agreements with X-ray crystallographic results published previously.

PMID- 9571054
TI  - Dissociation kinetics of RecA protein-three-stranded DNA complexes reveals a low
      fidelity of RecA-assisted recognition of homology.
AB  - We determined that the incorporation of one mismatch into RecA mediated synaptic
      complexes between oligonucleotide single-stranded DNAs and target duplex DNAs
      destabilizes the complex by 0.8 to 1.9 kcal/mol. This finding supports our
      previous result, that RecA binding per se can significantly decrease the loss in
      free energy associated with mismatch incorporation even in the absence of ATP
      hydrolysis. We show that the specificity is mostly driven by the dissociation
      process. We found that the relative destabilization induced by different
      mismatches depends on their position. Thus, while there is a good correlation
      between the ranking order of mismatches at the 5' end of synaptic complexes and
      mismatches in heteroduplexes (D-loops), there is no correlation between the
      ranking order for mismatches at the 3' end and mismatches in various DNA
      structures. This difference between the 5' and 3' ends of synaptic complexes
      agrees well with the established 5' to 3' polarity of the strand exchange
      promoted by RecA protein. The lack of a correlation between mismatches at the 3'
      end of synaptic complexes and mismatches in D-loops suggests the intermediate is
      probably not a canonical protein-free D-loop.

PMID- 9571053
TI  - Combinatorial effects of NusA and NusG on transcription elongation and Rho
      dependent termination in Escherichia coli.
AB  - The transcription factors NusA and NusG from Escherichia coli are modulators of
      the RNA polymerase elongation reaction and Rho-dependent transcription
      termination. NusA decreases the elongation rate and termination efficiency while
      NusG increases both activities. Both Nus factors are able to physically interact
      with Rho and with RNA polymerase. Experiments with purified components designed
      to determine whether these factors act independently or competitively showed that
      the change in elongation rate was a composite of their individual effects, that
      the combined effect on termination was dependent on the reaction conditions and
      that the two factors do not compete for their sites of action for either effect.
      The two factors were also found not to enhance significantly the slight (20%)
      inhibition of elongation caused by 200 microM guanosine 3',5'-bisdiphosphate
      (ppGpp) during transcription in vitro. The results also show that the effects of
      NusA and NusG on RNA polymerase elongation and Rho function are contrary to the
      inverse relationship between elongation and termination that is expected for a
      kinetic coupling of Rho action to RNA polymerase elongation. This property
      suggests that in addition to their known actions on RNA polymerase that influence
      the length of pausing, these factors act on some other rate-limiting step of the
      Rho-dependent termination process.

PMID- 9571055
TI  - The spacing between binding sites controls the mode of cooperative DNA-protein
      interactions: implications for evolution of regulatory circuitry.
AB  - The CI repressors of lambdoid phages bind cooperatively to adjacent binding
      sites. Although these binding sites are found at complex operators containing
      three binding sites, cooperative binding occurs only between dimers bound at two
      of the sites, a mode of binding termed pairwise cooperativity. At the level of
      regulation, pairwise cooperativity allows the proper operation of the genetic
      switch. At the mechanistic level, it has been proposed to result from steric
      distortion of the complex, such that a protein dimer bound to a central site
      cannot contact both flanking dimers because it "leans" towards one of the two
      sites. We have tested this model using the CI repressor of phage HK022. Previous
      work suggested that reducing the spacing between adjacent operators might allow
      cooperative interaction among three dimers, a mode of cooperativity we term
      extended. Using a set of synthetic templates, we have shown that reducing the
      spacing allows extended cooperativity among three binding sites. Accordingly, the
      mode of cooperativity changes qualitatively in response to changes in the inter
      site spacing. That is, the change in spacing has major functional consequences
      for the properties of the complex. We suggest that such changes can play
      important roles in the evolution of gene regulatory circuitry and of other
      processes involving nucleoprotein complexes.

PMID- 9571056
TI  - Functional characterization of the low-molecular-mass phosphotyrosine-protein
      phosphatase of Acinetobacter johnsonii.
AB  - The ptp gene of Acinetobacter johnsonii was previously reported to encode a low
      molecular-mass protein, Ptp, whose amino acid sequence, predicted from the
      theoretical analysis of the nucleotide sequence of the gene, exhibits a high
      degree of similarity with those of different eukaryotic and prokaryotic
      phosphotyrosine-protein phophatases. We have now overexpressed the ptp gene in
      Escherichia coli cells, purified the Ptp protein to homogeneity by a single-step
      chromatographic procedure, and analysed its functional properties. We have shown
      that Ptp can catalyse the dephosphorylation of p-nitrophenyl phosphate and
      phosphotyrosine, but has no effect on phosphoserine or phosphothreonine. Its
      activity is blocked by ammonium molybdate and sodium orthovanadate, which are
      strong inhibitors of phosphotyrosine-protein phosphatases, as well as by N
      ethylmaleimide and iodoacetic acid. Such specificity of Ptp for phosphotyrosine
      has been confirmed by the observation that it can dephosphorylate endogenous
      proteins phosphorylated on tyrosine, but not proteins modified on either serine
      or threonine. In addition, Ptp has been shown to quantitatively dephosphorylate
      two exogenous peptides, derived respectively from leech hirudin and human
      gastrin, previously phosphorylated on tyrosine. Moreover, site-directed
      mutagenesis experiments performed on Cys11 and Arg16, which are both present in
      the sequence motif (H/V)C(X5)R(S/T) typical of eukaryotic phosphotyrosine-protein
      phosphatases, have demonstrated that each amino acid residue is essential for the
      catalytic activity of Ptp. Taken together, these data provide evidence that Ptp
      is a member of the phosphotyrosine-protein phosphatase family. Furthermore, in
      search for the biological function of Ptp, we have found that it can specifically
      dephosphorylate an endogenous protein kinase, termed Ptk, which is known to
      autophosphorylate at multiple tyrosine residues in the inner membrane of
      Acinetobacter johnsonii cells. This represents the first identification of a
      protein substrate for a bacterial phosphotyrosine-protein phosphatase, and
      therefore constitutes a possible model for analysing the role of reversible
      phosphorylation on tyrosine in the regulation of microbial physiology.

PMID- 9571057
TI  - Quick-freeze deep-etch electron microscopy of the actin-heavy meromyosin complex
      during the in vitro motility assay.
AB  - Since mica is a substitute for glass in the in vitro actin motility assay, I
      examined the structure of heavy meromyosin (HMM) crossbridges supporting actin
      filaments by quick-freeze deep-etch replica electron microscopy. This method was
      capable of resolving the inter-domain cleft of the monomeric actin molecule. HMM
      heads that are not bound to actin, when observed by this technique, were straight
      and elongated in the absence of ATP but strongly kinked upon addition of ATP or
      ADP.inorganic vanadate to produce the putative long-lived analog of HMM
      ADP.inorganic phosphate. The low-magnification image of the ATP-containing acto
      HMM preparation showed features characteristic of sliding actin filaments on
      glass coverslips. At high magnification, all the HMM molecules were found
      attached to actin by one head with the majority projecting perpendicular to the
      filament axis, whereas in the absence of ATP, HMM exhibited two-head binding with
      a preponderance of molecules tilted at 45 degrees. Detailed examination of the
      shape of HMM heads involved in sliding showed a rounded, and flat appearance of
      the tip and comparatively thin neck portion as if the heads grasp actin filament,
      in contrast to rigor crossbridges which have a pear-shaped configuration with
      more gradual taper. Such configurations of HMM heads were essentially the same as
      I observed previously on acto-myosin subfragment-1 (S1) by the same technique,
      except for the presence of an additional neck portion of HMM which makes
      interpretaion of the images easier. Interestingly, under actively sliding
      conditions, very few heads were tilted in the rigor configuration. At first
      glance, the addition of ADP to the rigor-complex gave images rather like those
      obtained with ATP, but they turned out to be different. The contribution of the
      structural change of crossbridges to the force development is discussed.

PMID- 9571058
TI  - Reconstitution, characterisation and mass analysis of the pentacylindrical
      allophycocyanin core complex from the cyanobacterium Anabaena sp. PCC 7120.
AB  - The phycobilisome (PBS) of Anabaena sp. PCC 7120 was allowed to dissociate into
      its constituents and the resulting allophycocyanin (AP) fraction was purified.
      Its reconstitution yielded a complex which according to negative stain electron
      microscopy and spectral analysis was identical to the native pentacylindrical PBS
      core domain. Each cylinder of the central tricylindric unit was comprised of four
      AP (alphabeta)3 disks. Mass analysis using the scanning transmission electron
      microscope (STEM) showed the presence of 16 AP trimers in the intact
      reconstitute, which had a total mass of 1966(+/-66) kDa. Composition analysis
      indicated an AP trimer distribution of (AP-II):(AP-LCM):(AP-B):(AP-I)=6:2:2:6,
      i.e. an addition of two AP-I and two AP-II complexes compared to a tricylindrical
      PBS core domain. Therefore, we suggest that each supplementary half-core cylinder
      found in pentacylindrical AP core domains is comprised of one AP-I and one AP-II
      trimer, in agreement with the current model. The structural significance of the
      127 kDa core membrane linker polypeptide was further investigated by subjecting
      the AP core reconstitute to mild chymotryptic degradation. After isolation, the
      digested complex exhibited a tricylindrical appearance while STEM mass analysis
      confirmed the presence of only 12 AP complexes. Polypeptide analysis by SDS-PAGE
      and Edman degradation related the half-cylinder loss to cleavage of the Rep4
      domain of the core membrane linker polypeptide. On the basis of these data, a
      general model for the assembly of the three hemidiscoidal PBS types known to date
      is discussed.

PMID- 9571059
TI  - Nucleotide-dependent structural changes in dimeric NCD molecules complexed to
      microtubules.
AB  - Complexes consisting of motor domains of the kinesin-like protein ncd bound to
      reassembled brain microtubules were visualised using cryoelectron microscopy and
      helical image reconstruction. Different nucleotide-associated states of a dimeric
      construct (NDelta295-700) of ncd were analysed to reveal ADP-containing, AMP.PNP
      containing and empty (rigor) conformations. In these three states, each thought
      to mimic a different stage in ATP turnover, the double-headed motors attach to
      the microtubules by one head only, with the free head tethered in relatively
      fixed positions. The three structures differ both in the way the attached heads
      interact with tubulin and in the position of the tethered heads. In the strongly
      binding rigor and AMP.PNP (ATP-like) states, the attached head makes close
      contact with both subunits of a tubulin heterodimer. In the weakly bound ADP
      state, the contact made by the attached head with the monomer closer to the plus
      end appears to be more loose. Also, in the ATP-like state, the free head tilts
      nearer to the plus end than in the other two states. The data argue against model
      mechanisms in which a conformational change in the bound head guides the free
      head closer to its next binding site; on the contrary, the transition from ADP
      filled via rigor to the AMP.PNP (ATP-like) state of the bound head produces a
      small motion of the free head in the counter-productive direction. However, the
      observation that the tethered head points towards the minus end, in all three
      states, is consistent with the idea that the relative arrangement of the heads in
      a dimer is a major determinant of directionality.

PMID- 9571060
TI  - Structure determination of the three disulfide bond isomers of alpha-conotoxin
      GI: a model for the role of disulfide bonds in structural stability.
AB  - The three possible disulfide bonded isomers of alpha-conotoxin GI have been
      selectively synthesised and their structures determined by 1H NMR spectroscopy.
      alpha-Conotoxin GI derives from the venom of Conus geographus and is a useful
      neuropharmacological tool as it selectively binds to the nicotinic acetylcholine
      receptor (nAChR), a ligand-gated ion channel involved in nerve signal
      transmission. The peptide has the sequence ECCNPACGRHYSC-NH2, and the three
      disulfide bonded isomers are referred to as GI(2-7;3-13), GI(2-13;3-7) and GI(2
      3;7-13). The NMR structure for the native isomer GI(2-7;3-13) is of excellent
      quality, with a backbone pairwise RMSD of 0.16 A for a family of 35 structures,
      and comprises primarily a distorted 310 helix between residues 5 to 11. The two
      non-native isomers exhibit multiple conformers in solution, with the major
      populated forms being different in structure both from each other and from the
      native form. Structure-activity relationships for the native GI(2-7;3-13) as well
      as the role of the disulfide bonds on folding and stability of the three isomers
      are examined. It is concluded that the disulfide bonds in alpha-conotoxin GI play
      a crucial part in determining both the structure and stability of the peptide. A
      trend for increased conformational heterogeneity was observed in the order of
      GI(2-7;3-13)<GI(2-13;3-7)<GI(2-3;7-13). It was found that the peptide bond
      joining Cys2 to Cys3 in GI(2-3;7-13) is predominantly trans, rather than cis as
      theoretically predicted. These structural data are used to interpret the varying
      nAChR binding of the non-native forms.A model for the binding of native GI(2-7;3
      13) to the mammalian nAChR is proposed, with an alpha-subunit binding face made
      up of Cys2, Asn4, Pro5, Ala6 and Cys7 and a selectivity face, comprised of Arg9
      and His10. These two faces orient the molecule between the alpha and delta
      subunits of the receptor. The structure of the CCNPAC sequence of the native GI(2
      7;3-13) is compared to the structure of the identical sequence from the toxic
      domain of heat-stable enterotoxins, which forms part of the receptor binding
      region of the enterotoxins, but which has a different disulfide connectivity.

PMID- 9571061
TI  - Characterisation of urea-denatured states of an immunoglobulin superfamily domain
      by heteronuclear NMR.
AB  - The structural and dynamic properties of an immunoglobulin superfamily domain
      (IgSF), Ig 18', have been characterised by NMR at 285 K, in the presence of 4.2 M
      and 6.0 M urea, respectively. Analysis of chemical shift deviations, 3JHNHalpha
      coupling constants, sequential NOE pattern, and 15N relaxation data reveals that
      although the two urea-denatured states are highly disordered, some local turn
      like residual structures do exist. Moreover, some distinct differences between
      the properties of the two denatured states are observed. In 4.2 M urea-denatured
      Ig 18', regions 80-83 and 86-92 adopt turn-like conformations, furthermore,
      region 84-93 is involved in slow exchange processes that occur on a micro- to
      millisecond time-scale. In the 6.0 M urea-denatured state, these turn-like
      conformations are less occupied, and chemical exchange processes in region 84-93
      are largely reduced. In contrast, region 32-36 has persistent turn-like
      structures in both urea-denatured states. Some correlation between the spectral
      density function at 0 frequency, Jeff(0), for the urea-denatured states and the
      secondary structure elements of the folded state have been observed. Except for
      the terminal regions, residues corresponding to beta-strands have higher Jeff(0)
      values compared to residues corresponding to loops. The characterisation and
      comparison of the two urea-denatured states highlight residues that possess
      properties that may be crucial for the initiation of folding of this domain.

PMID- 9571062
TI  - Altered specificity mutations define residues essential for substrate positioning
      in xanthine dehydrogenase.
AB  - We describe the sequence changes of a number of mutations of the Aspergillus
      nidulans xanthine dehydrogenase (XDH). We have located the amino acids affected
      by these changes in the three-dimensional (3D) structure of aldehyde oxido
      reductase (MOP) from Desulfovibrio gigas, related to eukaryotic XDHs. Of these,
      two are loss of function mutations, mapping, respectively, in the molybdenum
      pterin co-factor (MoCo) domain and in the domain involved in substrate
      recognition. Changes in two amino acids result in resistance to the irreversible
      inhibitor allopurinol. In Arg911 two different changes, conserved among all XDHs
      and MOP but not in other aldehyde oxidases (AO), change the position of
      hydroxylation of the analogue 2-hydroxypurine from C-8 to C-6. A number of
      changes affect residues adjacent to the molybdenum or its ligands. Arg911 is
      positioned in the substrate pocket in a way that it can account for the
      positioning of purine substrates in relation to the MoCo reactive center,
      together with a glutamate residue, universally conserved among the XDHs (Glu833).

PMID- 9571063
TI  - Calculations on folding of segment B1 of streptococcal protein G.
AB  - We present an investigation of the folding thermodynamics and mechanism of
      segment B1 of streptococcal protein G. Molecular dynamics simulations of the
      fully solvated protein are used to probe thermodynamically significant states at
      different stages of folding. We performed several unfolding simulations to
      generate a database of initial conditions. The database is analyzed and
      clustered. The cluster centers extracted from this database were then used as
      starting points for umbrella sampling of the folding free energy landscape under
      folding conditions. The resulting sampling was combined with the weighted
      histogram analysis method. One and two-dimensional free energy surfaces were
      constructed along several order parameters and used to analyze the folding
      process. Our findings indicate that an initial collapse precedes the formation of
      significant native structure. Elements of local structure originate in the
      regions of the protein shown to have higher H/2H exchange protection factors in
      early stages of folding. A non-native contact, observed experimentally at the N
      terminus of the alpha-helix in a peptide excised from the protein, is seen to pre
      organize the chain in early stages of folding. Collapse and early structure
      formation yields a compact globule with a significant number of water molecules
      present. Desolvation of the protein core is coincident with the final stages of
      folding from the compact state.

PMID- 9571064
TI  - Structural determinants in the sequences of immunoglobulin variable domain.
AB  - To determine the general relation between the sequence and structure of variable
      domains of immunoglobulins we have carried out an analysis of their atomic
      structures, some 5300 different expressed sequences and the human germline gene
      segments. Variable domains are formed by two beta-sheets, packed face to face,
      and the inter-strand turns. Comparison of the different known structures shows
      that they have a core of 76 residues which has the same main-chain conformation
      in all structures. This common core contains almost all of the beta-sheet
      structure and three inter-strand turns. The regions that differ in conformation
      are the three hypervariable regions, three other inter-strand turns and a few
      adjacent residues. The 5300 expressed sequences currently known for variable
      domains were examined to determine the residues that occur at the 76 sites.
      Ignoring site conservations that occur for functional reasons, there are eight
      sites that have the same residue in almost all sequences; 12 that have one of a
      small group of very similar residues, and 52 where the chemical character of the
      residues is strongly conserved but not their volume. The role of residues at each
      site in the core was determined from the examination of their accessible surface
      areas, contacts, packing and buried side-chain hydrogen bonds. The most strongly
      conserved sites form the "deep" structure of the domain at the centre of the
      interface between the beta-sheets. It includes eight invariant sites and 11 sites
      that have one of a set of very similar residues. Around the deep structure there
      are buried hydrophobic residues that, in different variable domains, can differ
      greatly in volume. These differences in volume are accommodated by conformational
      changes in turn regions that are outside the common core. On the surface nearly
      all residues not involved in function or turn conformations strongly conserve
      hydrophilic or neutral residues. The implications of these results for the
      general relations between the sequence and structure of proteins are discussed.

PMID- 9571069
TI  - EDITORIAL
AB  - Copyright

PMID- 9571065
TI  - Conformational sampling of CDR-H3 in antibodies by multicanonical molecular
      dynamics simulation.
AB  - The diversity in the lengths and the amino acid sequences of the third
      complementarity determining region of the antibody heavy chain (CDR-H3) has 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. Enhanced conformational sampling of two different CDR-H3s
      was performed by multicanonical molecular dynamics (multicanonical MD) simulation
      while restricting the base structures, with and without the other surrounding CDR
      segments. The results showed that the multicanonical MD sampled a much larger
      conformational space than the conventional MD, independent of the initial
      conformations of the simulations. When the other CDRs surrounding the CDR-H3
      segments were included in the calculations, the predominant conformations at 300
      K corresponded to the X-ray crystal structures. When only the single CDR-H3 loops
      were considered with the restricted base structures, a greater number of
      different conformations were sampled as putative loops, but only a small number
      of stable conformations appeared at 300 K. Analyses of the resultant
      conformations revealed a structural role for the glycine, when it is located at
      position three residues before the last residue of CDR-H3 (Gly-X-X-last residue),
      coincident with the statistical tendencies of many antibody crystal structures.
      This reflects the general consistency between the energetically stable
      conformations and the empirically observed conformations. The current method is
      expected to be applicable to the structural modeling and the design of
      antibodies, especially for the inherently flexible loops.

PMID- 9571070
TI  - Generation, identification, and recovery of mouse mutations.
AB  - Mouse mutations can be generated by a variety of techniques including those that
      rely on inducing agents such as X rays or chemicals and those that involve
      genetic manipulations such as in transgene insertions and gene knockouts. Each
      technique has its advantages and disadvantages. Inducing agents are often more
      efficient when random mutations in as yet unknown genes are desired. In contrast,
      genetic manipulations are advantageous when the mutagenesis needs to be targeted
      to certain genes or regions. Once these mutations are produced, they must be
      systematically identified and characterized to confirm their distinction from
      other known mutations and environmental influences. Allelism and linkage tests
      should be performed. Finally, methods for maintaining these mutations should be
      applied so that studies of them can be pursued in the most efficient manner.

PMID- 9571071
TI  - Genetic mapping of the mouse genome.
AB  - This article provides an introduction to genetic mapping for scientists who wish
      to map specific genes or mutant phenotypes in the mouse. The basic principles of
      genetic mapping and the different types of genetic markers available are
      described in the first two sections of the chapter. The theoretical and empirical
      principles necessary to consider when designing mapping experiments are reviewed
      in the third section. Protocols for mapping phenotypic traits and cloned genes
      are detailed in the fourth and fifth sections.

PMID- 9571072
TI  - Physical mapping of the mouse genome.
AB  - This review is intended to provide an overview of techniques and a source of
      reagents for physical mapping of the mouse genome. It focuses on those
      applications, methods, or resources unique to the mouse and on the generation of
      comparative physical maps. The reference list is not comprehensive; rather,
      recent reviews on each topic and selected representative examples are given.

PMID- 9571073
TI  - Positional cloning and gene identification.
AB  - After genetic mapping and physical representation of a particular genomic region
      containing the gene underlying a particular Mendelian trait, a successful
      positional cloning strategy depends on the efficient detection and analysis of
      genes in the critical interval. Several gene detection strategies are presently
      available to compile an inventory of genes from large genomic regions. Here, the
      principle of these methods is briefly reviewed and their relative value for
      positional cloning projects compared.

PMID- 9571074
TI  - DNA sequence analysis and comparative sequencing.

PMID- 9571075
TI  - Informatics for mouse genetics and genome mapping.
AB  - Bioinformatics has become an essential part of biological research. The rapid
      pace of technology development and the ability to carry out biological
      experimentation in large scale require computerized systems for data management,
      analysis, and display. Experimentation with the mouse, a major model organism of
      the Human Genome Initiative, has intensified the need for bioinformatics tools
      for mouse mapping and genome analysis. This article describes the Mouse Genome
      Database in the United States, a primary resource for mouse genomic data, as well
      as resources at the Mammalian Genetics Unit in the United Kingdom and the Animal
      Genome Database of Japan. Internet addresses are provided for major genetic and
      physical mapping resources, major genome data sites, and resources of molecular
      information.

PMID- 9571076
TI  - Complex traits and polygenic inheritance in the mouse.
AB  - Polygenic inheritance has recently become an increasingly active field of
      research due to the availability of techniques allowing in-depth screening of
      genetic markers across the entire genome. The mouse is being used both in its own
      right and as a model system for certain human traits. The advantages and
      disadvantages of the mouse for such studies are outlined and in this context, the
      adequacy of the mouse as a model for polygenic traits in humans is discussed. A
      detailed overview of the approaches and methods used in the analysis of polygenic
      inheritance in the mouse is presented.

PMID- 9571077
TI  - Exploring gene function: use of yeast artificial chromosome transgenesis.
AB  - Transgenesis is a very powerful tool in functional analysis of proteins and
      control of gene expression. One of the main drawbacks has been the low levels of
      expression, lack of tissue specificity, and inappropriate expression frequently
      observed for transgenes made with small plasmid-based constructs. The use of much
      larger DNA fragments cloned in yeast artificial clones (YACs), bacterial
      artificial clones, or P1-based artificial clones has been found to give much
      better levels of expression, generally very close to that of an endogenous gene,
      and tissue-specific expression matching that of the endogenous gene. In addition,
      the large DNA can easily be subtly modified by homologous recombination. This
      article describes the background and methods of YAC transgenesis.

PMID- 9571079
TI  - European Training Program in Microseparation Techniques
AB  - Copyright

PMID- 9571078
TI  - Analysis and identification of imprinted genes.
AB  - Genomic imprinting in mammals results in the unequal expression of the two
      parental alleles of specific genes. The existence of imprinting in the mouse
      emerged from nuclear transplantation studies and from the abnormal phenotypes
      associated with uniparental inheritance of particular chromosome segments. Over
      the past 5 years, 20 or so imprinted genes have been identified. This has
      emphasized the important roles played by some imprinted genes in development,
      permitted a description of the epigenetic properties associated with imprinting,
      and provided the first insights into the regulation of imprinting. In this
      article, we discuss the generation of experimental material in which imprinting
      effects can be analyzed, review the properties of imprinted genes, and discuss
      how to examine them using state-of-the-art techniques. Finally, we consider the
      means by which new imprinted genes can be identified.

PMID- 9571080
TI  - Advent of computer technology.

PMID- 9571081
TI  - Computer modeling of size and shape descriptors of alpha 1-adrenergic receptor
      antagonists and quantitative structure-affinity/selectivity relationships.
AB  - Computational chemistry and molecular modeling procedures allow us to define and
      compute ad hoc size and shape descriptors on the different prototropic forms
      assumed by drugs in biotest solutions. Together with experimental data measured
      on a well-identified target receptor, these descriptors are essential elements
      for obtaining simple, consistent, comparable, and easily interpretable
      theoretical quantitative structure-activity relationship (QSAR) models based on
      the ligand similarity-target receptor complementarity paradigm. In this context,
      quantitative size and shape affinity/subtype selectivity relationships have been
      modeled for a large set of very heterogeneous alpha 1a-, alpha 1b-, and alpha 1c
      adrenergic receptor antagonists. The linear QSAR models generated have been
      validated by predicting both binding affinity and selectivity of a test set of
      noncongeneric antagonists. The satisfactory results obtained highlight both the
      simplicity and the versatility of the approach presented.

PMID- 9571083
TI  - Quantitative structure-based modeling applied to characterization and prediction
      of chemical toxicity.
AB  - Quantitative modeling methods, relating aspects of chemical structure to
      biological activity, have long been applied to the prediction and
      characterization of chemical toxicity. The early linear free-energy approaches of
      Hansch and Free Wilson provided a fundamental scientific framework for the
      quantitative correlation of chemical structure with biological activity and
      spurred many developments in the field of quantitative structure-activity
      relationships (QSARs). In addition to modeling of chemical toxicity, these
      methods have been extensively applied to modeling of medicinal properties of
      chemicals. However, there are important differences in the nature and objectives
      of these two applications, which have led to the evolution of different modeling
      approaches (namely, the need for treating sets of noncongeneric toxic compounds).
      In this paper are discussed those approaches to chemical toxicity that have taken
      a more "personalized" configuration and have undergone implementation into
      software programs able to perform the various steps of the assessment of the
      hazard posed by the chemicals. These models focus both on a variety of
      toxicological endpoints and on key elements of toxicity mechanisms, such as
      metabolism.

PMID- 9571082
TI  - Use of 3D QSAR methodology for data mining the National Cancer Institute
      Repository of Small Molecules: application to HIV-1 reverse transcriptase
      inhibition.
AB  - A three-dimensional (3D) stereoelectronic pharmacophore developed from a 3D
      quantitative structure-activity relationship (QSAR) investigation formed the
      basis of the development of a two-phase data-mining methodology to uncover novel
      leads to inhibit human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase at the nonnucleoside binding site. The database searching phase
      employed a field search for ligand requirements (such as log P, molecular volume)
      that were accessible from the database keys. Next, a 3D database search was
      performed that used an automated fitting procedure and the calculation of several
      binding parameters. These binding parameters were used to test the hits by a
      discriminant function that was previously trained to recognize active from
      inactive analogs. During the structural evaluation phase of the methodology,
      conformational properties and complementary receptor features of the hits were
      examined by 2D and 3D evaluations, which were followed by molecular modeling
      investigations. When this method was applied to a test database, an improvement
      from 6.4% to 100% active analogs was achieved.

PMID- 9571084
TI  - Stacking interactions and intercalative DNA binding.
AB  - The DNA-binding properties of many ligands can be rationalized on the basis of
      their structural and electronic complementarity with the functional groups
      present in the minor and major grooves of particular DNA sequences. Specific
      hydrogen bonding patterns are particularly useful for the purpose of sequence
      recognition. Less obvious, however, is the influence of base composition on the
      conformational preferences of individual base steps and on the binding of
      intercalating moieties which become sandwiched between contiguous base pairs.
      Improved knowledge of stacking interactions may lead to a better understanding of
      the architecture and inherent flexibility of particular DNA sequences and may
      provide insight into the principles that dictate the structural changes and
      specificity patterns observed in the binding of some intercalating ligands to
      DNA.

PMID- 9571085
TI  - Homology modeling with low sequence identity.
AB  - The field of protein structure prediction is evolving rapidly and in the last few
      years a number of new methods have been developed and evaluated. However,
      comparative modeling, or modeling by homology, is still the method of choice when
      the unknown protein shares any significant sequence similarity with a protein of
      known structure. The accuracy of the method is highly dependent on the degree of
      similarity between the target protein and that used as a template. Nevertheless,
      careful consideration of all the steps performed in the modeling procedure allows
      useful information to be obtained also from a model based on very low sequence
      identity.

PMID- 9571086
TI  - Ab initio modeling and molecular dynamics simulation of the alpha 1b-adrenergic
      receptor activation.
AB  - This work describes the ab initio procedure employed to build an activation model
      for the alpha 1b-adrenergic receptor (alpha 1b-AR). The first version of the
      model was progressively modified and complicated by means of a many-step
      iterative procedure characterized by the employment of experimental validations
      of the model in each upgrading step. A combined simulated (molecular dynamics)
      and experimental mutagenesis approach was used to determine the structural and
      dynamic features characterizing the inactive and active states of alpha 1b-AR.
      The latest version of the model has been successfully challenged with respect to
      its ability to interpret and predict the functional properties of a large number
      of mutants. The iterative approach employed to describe alpha 1b-AR activation in
      terms of molecular structure and dynamics allows further complications of the
      model to allow prediction and interpretation of an ever-increasing number of
      experimental data.

PMID- 9571088
TI  - Brownian dynamics simulation of protein-protein diffusional encounter.
AB  - Protein association events are ubiquitous in biological systems. Some protein
      associations and subsequent responses are diffusion controlled in vivo. Hence, it
      is important to be able to compute bimolecular diffusional association rates for
      proteins. The Brownian dynamics simulation methodology may be used to simulate
      protein-protein encounter, compute association rates, and examine their
      dependence on protein mutation and the nature of the physical environment (e.g.,
      as a function of ionic strength or viscosity). Here, the theory for Brownian
      dynamics simulations is described, and important methodological aspects,
      particularly pertaining to the correct modeling of electrostatic forces and
      definition of encounter complex formation, are highlighted. To illustrate
      application of the method, simulations of the diffusional encounter of the
      extracellular ribonuclease, barnase, and its intracellular inhibitor, barstar,
      are described. This shows how experimental rates for a series of mutants and the
      dependence of rates on ionic strength can be reproduced well by Brownian dynamics
      simulations. Potential future uses of the Brownian dynamics method for
      investigating protein-protein association are discussed.

PMID- 9571087
TI  - Essential dynamics from NMR clusters: dynamic properties of the Myb DNA-binding
      domain and a hinge-bending enhancing variant.
AB  - Application of the "essential dynamics" method to the NMR cluster of structures
      for the R2R3 DNA-binding domain of the mouse c-Myb transcriptional activator is
      described. Using this method, large concerted fluctuations of atoms are extracted
      showing a hinge-bending motion between the two (R2 and R3) Myb repeats on the
      basis of NMR data alone. Molecular dynamics simulation of the same protein
      allowed quantitative comparison of the large concerted motions calculated from
      experimental and theoretical data, showing a significant degree of similarity.
      Detailed inspection of the motions reveals a conserved proline that plays a key
      role in determining hinge flexibility. The proline-to-alanine mutation at this
      position, which has previously been characterized biochemically, was subjected to
      molecular dynamics and subsequent essential dynamics analysis. The hinge-bending
      motion between the two repeats was found to be enhanced for the mutant. The
      approach described should have general applications, predicting the effect of
      mutations on protein dynamic properties of other proteins.

PMID- 9571089
TI  - Using theory and simulation to understand permeation and selectivity in ion
      channels.
AB  - It is clear that the function of ion channels must flow from their structure.
      With recent advances in computational power and methodology, it appears feasible
      to correlate structure to ion channel permeation at an atomistically detailed
      level of description. The overall strategy is to structure the calculations in a
      hierarchy, ranging from coarse-grained thermodynamic and kinetic descriptions to
      fine-grained molecular dynamics descriptions with atomic detail. Each level of
      description is connected to the others by appropriate statistical mechanical
      theory. The coarse-grained descriptions can be correlated directly with
      electrophysiological experiment. The fine-grained descriptions are used to
      parameterize the coarse-grained descriptions and to describe the permeation
      process at the most detailed level. This strategy has so far had varying degrees
      of success. It has successfully described water permeation through lipid bilayers
      and gramicidin channels. It has revealed the essential events of ion permeation
      through gramicidin channels at an atomistically detailed level. The role of
      channel protein motions in permeation has been elucidated. However, it appears
      that force fields used to describe molecular dynamics must be refined further to
      achieve completely accurate predictions of the permeation of such small ions as
      sodium. Channels with more complex structure and more multiion occupancy than
      gramicidin pose major computational challenges with respect to sampling protein
      conformations and ion distributions involved in the permeation process. Possible
      approaches to meeting these challenges are discussed.

PMID- 9571090
TI  - Control of Spinning Sidebands in High Resolution NMR Spectroscopy
AB  - The presence of spinning sidebands can severely compromise the detection of low
      molarity analytes. Spinning sidebands have traditionally been minimized by
      improving the magnetic field homogeneity and by varying the spinning of the
      sample in a linear fashion during data acquisition. The effect of the latter is
      to spread the spinning sideband intensity over a range of frequencies so that the
      final result is a spinning sideband whose shape reflects the distribution of
      spinning speeds. We have designed a customized profile of spinner speed variation
      that optimizes the reduction of spinning sidebands. The customized profile is
      based on theoretical considerations of how the intensity of sidebands vary with
      the rate of sample rotation and also compensates for the mechanical design of the
      spinner mechanism. The result is a unique combination of an exponential increase
      in gas flow rate to balance the theoretical considerations coupled with a
      strategically placed rapid change in air flow to annul the sluggish response of
      the spinning mechanism to acceleration. The resulting sideband shape is a broad,
      flat, square step in the baseline that is least likely to interfere with low
      molarity analyte peaks. Copyright 1998 Academic Press.

PMID- 9571091
TI  - Rotational Motion of a Solute Molecule in a Highly Viscous Liquid Studied by 13C
      NMR: 1,3-Dibromoadamantane in Polymeric Chlorotrifluoroethene
AB  - The viscosity-dependent retarding effect of a polymeric solvent on the rotation
      of small solute molecules is investigated by 13C NMR relaxation measurements. It
      is found that the relaxation data of 1,3-dibromoadamantane in highly viscous
      polymeric chlorotrifluoroethene can be explained neither by isotropic nor by
      realistic anisotropic tumbling in a single environment. The experimental data are
      rationalized in terms of fast exchange between at least two environments with
      correlation times differing by up to two orders of magnitude. The study shows
      that a uniform retardation of molecular tumbling by a polymeric solvent,
      desirable for shifting the NMR observation window in studies of intramolecular
      mobility, is not always feasible. Copyright 1998 Academic Press.

PMID- 9571092
TI  - The role of specific side groups and pH in magnetization transfer in polymers.
AB  - The nature of water-macromolecule interactions in aqueous model polymers has been
      investigated using quantitative measurements of magnetization transfer. Cross
      linked polymer gels composed of 94% water, 3% N,N'-methylene-bis-acrylamide, and
      3% functional monomer (acrylamide, methacrylamide, acrylic acid, methacrylic
      acid, 2-hydroxyethyl-acrylate, or 2-hydroxyethyl-methacrylate) were studied.
      Water-macromolecule interactions were modified by varying the pH and specific
      functional group on the monomer. The magnitudes of the interactions were
      quantified by measuring the rate of proton nuclear spin magnetization exchange
      between the polymer matrix and the water. This rate was highly sensitive to the
      presence of carboxyl side groups on the macromolecule. However, the dependence of
      the rate on pH was not consistent with simple acid/base-catalyzed chemical
      exchange, and instead, the data suggest that multiequilibria proton exchange, a
      wide distribution in surface group pK values, and/or a macromolecular structural
      dependence on pH may play a significant role in magnetization transfer in polymer
      systems. These model polymer gels afford useful insights into the relevance of
      chemical composition and chemical dynamics on relaxation in tissues.

PMID- 9571093
TI  - Multiplicity-Selective Coherence Transfer Steps for the Design of Amino Acid
      Selective Experiments-A Triple-Resonance Experiment Selective for Asn and Gln
AB  - A multiplicity-selective coherence transfer step is discussed, that can replace
      the normal INEPT transfer in triple-resonance experiments. Depending on the pulse
      sequence in which they are implemented, amino acid-selective experiments will be
      created. Two experiments selective for Asn and Gln are proposed. Copyright 1998
      Academic Press.

PMID- 9571094
TI  - Demonstrating the Spatial Resolution of Field Gradient NMR
AB  - In recent years, field gradient NMR has become a method of increasing importance
      in measuring very small dislocations of molecules. Rough estimations indicate
      that, by utilizing large field gradients, one should be able to detect motions
      down to the 10-nm scale. However, this limit has not yet been experimentally
      detected. In this paper, we present a method that allows the direct measurement
      of the spatial resolution of field gradient NMR. For our experimental setup,
      utilizing an extremely large static field gradient of about 180 T m-1, we find a
      lower limit of 7 nm, thus for the first time confirming the expected resolution.
      Furthermore, we discuss the effect of unwanted vibrations as a limiting factor of
      the method. Copyright 1998 Academic Press.

PMID- 9571095
TI  - Complete Dipolar Decoupling of 13C and Its Use in Two-Dimensional Double-Quantum
      Solid-State NMR for Determining Polymer Conformations
AB  - A multiple-pulse technique for complete dipolar decoupling of directly bonded 13C
      labeled sites is described. It achieves significant spectral simplifications in a
      recently introduced two-dimensional double-quantum solid-state NMR experiment for
      determining torsion angles. Both homonuclear and heteronuclear dipolar couplings
      are removed by combining a 13C multiple-pulse sequence with continuous-wave
      irradiation on the protons. The 13C sequence has a fundamental 10-pulse cycle
      which is a significantly modified magic-sandwich-echo sequence. The crucial
      heteronuclear decoupling is achieved by breaking the 360 degrees "inner" pulses
      in the magic sandwich into 90 degrees pulses and spacing them by 1H 360 degrees
      pulse lengths. Spectral artifacts typical of multiple-pulse sequences are
      eliminated by phase shifts between cycles. In contrast to many other multiple
      pulse decoupling sequences, the long window in the cycle is the dwell time and
      can be longer than the inverse dipolar coupling, which makes the sequence
      practical for direct detection even with long pulse ring-down times. A
      modification of the sequence to scale the chemical shift and increase the
      effective spectral width is also presented. The 1D and double-quantum 2D
      experiments are demonstrated on polyethylene with 4% 13C-13C spin pairs. The
      potential of this approach for distinguishing segmental conformations is
      illustrated by spectral simulations of the two-dimensional ridge patterns that
      correlate double-quantum and single-quantum chemical-shift anisotropies.
      Copyright 1998 Academic Press.

PMID- 9571096
TI  - Experimental Determination of Four-Time Stimulated Echoes in Liquids, Colloidal
      Suspensions, and Crystals
AB  - Four-time stimulated echo experiments have been used to monitor the temporal
      evolution of the reorientation rates of deuterated molecules or colloidal
      suspensions. We present extended phase cycles for this seven-pulse experiment. In
      order to test its performance three vastly different materials are chosen. These
      include a crystal in which the molecules carry out well-defined 180 degrees flips
      and a supercooled liquid characterized by a distribution of jump angles centered
      around 10 degrees. As an example for rotational diffusion, data on a concentrated
      suspension of polystyrene spheres in a viscous medium are presented. Copyright
      1998 Academic Press.

PMID- 9571097
TI  - Spin-Echo Mapping Spectroscopy Applied to NQR
AB  - A theoretical description of nuclear spin-echo Fourier-transform mapping
      spectroscopy (NSEFTMS) for broad NQR lines is derived from the time-domain spin
      echo theory for a spin I = 32 system. The expression found for the effective
      broadband RF excitation profile is similar to that in NMR spectroscopy. The main
      difference is the angular dependence of the nutation frequency, but this does not
      change the overall behavior. It is also shown that the maximum of the spin echo
      occurs at time t = tau + 2 2pitw1 after the second pulse, and that if the signal
      is acquired from this point, the phase-adjustment problem due to the off
      resonance effect is avoided. A study of 35Cl NQR broad lines in molecular alloys
      of (p-dichlorobenzene)(1-x) (p-dibromobenzene)x at different temperatures and in
      the incommensurate phase of bis-(4-chorophenyl) sulfone at 77 K has been used as
      an example of the application of the method. The NSEFTMS method in NQR provides
      an efficient alternative to the time-consuming point-by-point scanning technique
      for the study of broad lines in solids, in particular when some sharp features
      exist. Copyright 1998 Academic Press.

PMID- 9571098
TI  - Effective Gradients in Porous Media Due to Susceptibility Differences
AB  - In porous media, magnetic susceptibility differences between the solid phase and
      the fluid filling the pore space lead to field inhomogeneities inside the pore
      space. In many cases, diffusion of the spins in the fluid phase through these
      internal inhomogeneities controls the transverse decay rate of the NMR signal. In
      disordered porous media such as sedimentary rocks, a detailed evaluation of this
      process is in practice not possible because the field inhomogeneities depend not
      only on the susceptibility difference but also on the details of the pore
      geometry. In this report, the major features of diffusion in internal gradients
      are analyzed with the concept of effective gradients. Effective gradients are
      related to the field inhomogeneities over the dephasing length, the typical
      length over which the spins diffuse before they dephase. For the CPMG sequence,
      the dependence of relaxation rate on echo spacing can be described to first order
      by a distribution of effective gradients. It is argued that for a given
      susceptibility difference, there is a maximum value for these effective
      gradients, gmax, that depends on only the diffusion coefficient, the Larmor
      frequency, and the susceptibility difference. This analysis is applied to the
      case of water-saturated sedimentary rocks. From a set of NMR measurements and a
      compilation of a large number of susceptibility measurements, we conclude that
      the effective gradients in carbonates are typically smaller than gradients of
      current NMR well logging tools, whereas in many sandstones, internal gradients
      can be comparable to or larger than tool gradients. Copyright 1998 Academic
      Press.

PMID- 9571099
TI  - Sensitivity of Saturation Transfer Electron Spin Resonance Extended to Extremely
      Slow Mobility in Glassy Materials
AB  - A novel extension of the saturation transfer (ST) ESR technique that enables the
      determination of extremely long rotational correlation times of nitroxide spin
      labels up to values around 10(4) s is proposed. The method is based on the
      observation that the integral of ST-ESR spectra is sensitive to the spin-lattice
      relaxation time of the electron of the spin label, which in turn is directly
      dependent upon the rotational correlation time. The method is applied to the spin
      label TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) in glycerol. From
      the known viscosity data and the related rotational correlation times of the
      TEMPOL spin label in glycerol, the rotational correlation times of unknown
      samples can be determined. The method is especially applicable to systems with a
      very high viscosity, such as glassy materials. The method is applied to a 20 wt%
      glucose-water mixture in the glassy state, giving a value for the highest
      limiting rotational correlation time of about 10(3) s at a temperature of 45 K
      below the glass transition temperature of this system. This is an extension by
      six decades for the rotational correlation time, as compared to the current
      application of ST-ESR. Copyright 1998 Academic Press.

PMID- 9571100
TI  - An NMR investigation of the conformational effect of nitroxide spin labels on Ala
      rich helical peptides.
AB  - Nitroxide spin labels, in conjunction with electron spin resonance (ESR)
      experiments, are extensively employed to probe the structure and dynamics of
      biomolecules. One of the most ubiquitous spin labeling reagents is the
      methanethiosulfonate spin label which attaches a spin label selectively to Cys
      residues via a disulfide bond (Cys-SL). However, the actual effect of the
      nitroxide spin label upon the conformation of the peptide or protein cannot be
      unambiguously determined by ESR. In this study, a series of 16-residue Ala-rich
      helical peptides was characterized by nuclear magnetic resonance techniques. The
      C alpha H chemical shift analysis, NOEs, and 3JNH alpha coupling constants for
      peptides with no Cys, free Cys, and Cys-SL (with the N-O group reduced) were
      compared. These results indicate that while replacement of an Ala with a Cys
      residue causes a loss of overall helical structure, the Cys-SL residue is helix
      supporting, as would be expected for a non-beta-branched aliphatic amino acid.
      Thus, the Cys-SL residue does not perturb helical structure and, instead,
      exhibits helix-stabilizing characteristics similar to that found for Ala, Met,
      and Leu.

PMID- 9571101
TI  - Radiofrequency-Driven and Slow-Magic-Angle-Sample-Spinning Polarization-Transfer
      Techniques: A Comparative Study
AB  - The rate constant of radiofrequency-driven (RF-driven) polarization transfer and
      that of polarization transfer under slow-magic-angle sample spinning (S-MAS) are
      compared using a model system, polycrystalline alpha-alpha'-13C2-phthalic acid.
      While the rate constant under RF irradiation in static samples strongly depends
      on the orientation of the internuclear vector, the rate constant under S-MAS is
      hardly sensitive to that orientation and, thus, depends almost exclusively on the
      internuclear distance. Consequently, polarization-transfer rate constants
      obtained under S-MAS can be interpreted more simply when used to study local
      order in polycrystalline or amorphous solids. Copyright 1998 Academic Press.

PMID- 9571102
TI  - Sensitivity Enhancement by Matched Microwave Pulses in One- and Two-Dimensional
      Electron Spin Echo Envelope Modulation Spectroscopy
AB  - The concept of microwave pulse matching is applied to three-pulse electron spin
      echo envelope modulation and sublevel correlation (HYSCORE) spectroscopy. Matched
      pulses enhance the efficiency of forbidden transfers and may drastically increase
      the signal intensity of basic frequency and combination frequency transitions in
      these conventional pulse EPR experiments. The theory of matched pulses is
      extended to the case of strong and largely isotropic hyperfine interactions, and
      numerical simulations are presented to gain a deeper insight into the inner
      working of the matched-pulse approach. It is shown that the enhancement of
      combination frequencies in matched HYSCORE can be used to determine the relative
      sign of hyperfine coupling constants as well as the number of equivalent nuclei.
      The enormous capacity of the approach is demonstrated on ordered and disordered
      systems. In particular, it is shown that in HYSCORE experiments the signal-to
      noise ratio improvement for strongly coupled nitrogens and for proton combination
      peaks may be considerably larger than one order of magnitude, corresponding to a
      reduction in measuring time of more than a factor of 100. Copyright 1998 Academic
      Press.

PMID- 9571104
TI  - Multilayer Gradient Coil Design
AB  - In standard cylindrical gradient coils consisting of wires wound in a single
      layer, the rapid increase in coil resistance with efficiency is the limiting
      factor in achieving very large magnetic field gradients. This behavior results
      from the decrease in the maximum usable wire diameter as the number of turns is
      increased. By adopting a multilayer design in which the coil wires are allowed to
      spread out into multiple layers wound at increasing radii, a more favorable
      scaling of resistance with efficiency is achieved, thus allowing the design of
      more powerful gradient coils with acceptable resistance values. By extending the
      theory used to design standard cylindrical gradient coils, we have developed
      mathematical expressions which allow the design of multilayer coils, and the
      evaluation of their performance. These expressions have been used to design a
      four-layer, z-gradient coil of 8 mm inner diameter, which has an efficiency of
      1.73 Tm-1 A-1, a resistance of 1.8 Omega, and an inductance of 50 uH. This coil
      produces a gradient which deviates from linearity by less than 5% within a
      central cylindrical region of 4.5 mm length and 4.5 mm diameter. A coil has been
      constructed from this design and tested in simple imaging and pulsed gradient
      spin echo experiments. The resulting data verify the predicted coil performance,
      thus demonstrating the advantages of using multilayer coils for experiments
      requiring very large magnetic field gradients. Copyright 1998 Academic Press.

PMID- 9571103
TI  - Activation of visuomotor systems during visually guided movements: a functional
      MRI study.
AB  - The dorsal stream is a dominant visuomotor pathway that connects the striate and
      extrastriate cortices to posterior parietal areas. In turn, the posterior
      parietal areas send projections to the frontal primary motor and premotor areas.
      This cortical pathway is hypothesized to be involved in the transformation of a
      visual input into the appropriate motor output. In this study we used functional
      magnetic resonance imaging (fMRI) of the entire brain to determine the patterns
      of activation that occurred while subjects performed a visually guided motor
      task. In nine human subjects, fMRI data were acquired on a 4-T whole-body MR
      system equipped with a head gradient coil and a birdcage RF coil using a T2*
      weighted EPI sequence. Functional activation was determined for three different
      tasks: (1) a visuomotor task consisting of moving a cursor on a screen with a
      joystick in relation to various targets, (2) a hand movement task consisting of
      moving the joystick without visual input, and (3) a eye movement task consisting
      of moving the eyes alone without visual input. Blood oxygenation level-dependent
      (BOLD) contrast-based activation maps of each subject were generated using period
      cross-correlation statistics. Subsequently, each subject's brain was normalized
      to Talairach coordinates, and the individual maps were compared on a pixel by
      pixel basis. Significantly activated pixels common to at least four out of six
      subjects were retained to construct the final functional image. The pattern of
      activation during visually guided movements was consistent with the flow of
      information from striate and extrastriate visual areas, to the posterior parietal
      complex, and then to frontal motor areas. The extensive activation of this
      network and the reproducibility among subjects is consistent with a role for the
      dorsal stream in transforming visual information into motor behavior. Also
      extensively activated were the medial and lateral cerebellar structures,
      implicating the cortico-pontocerebellar pathway in visually guided movements.
      Thalamic activation, particularly of the pulvinar, suggests that this nucleus is
      an important subcortical target of the dorsal stream.

PMID- 9571105
TI  - Complete Determination of Nitrogen Quadrupole and Hyperfine Tensors in an
      Oxovanadium Complex by Simultaneous Fitting of Multifrequency ESEEM Powder
      Spectra
AB  - One-dimensional C- and X-band as well as two-dimensional X-band ESEEM experiments
      were performed on the complex oxobis(2-methylquinolin-8-olato) vanadium(IV) in
      frozen solution. A 14N ESEEM simulation strategy based on initial first- and
      second-order perturbation analysis of peak positions in orientationally selected
      ESEEM spectra is presented. The constraint parameters extracted enable one to
      reduce the number of free fitting parameters for each nitrogen from 10 to 4.
      These are the alpha, beta resp. the phi, theta Euler angles of the NQI and the
      HFI tensor defined in the coordinate system of the axial g tensor. The local
      symmetry of the complex allows one to reduce the number of free parameters to two
      angles only. Subsequently, a grid search in the remaining Euler space produced
      the starting parameters for the final fit of the 14N hyperfine and quadrupole
      tensors. The anisotropic nitrogen hyperfine interaction tensor was found to be
      strongly nonaxial (0.06, 0.51, -0.57) MHz with the components significantly
      smaller than the isotropic hyperfine constant -6.18 MHz. In contrast, the
      quadrupole tensor with K = 0.58 MHz is close to axial (eta = 0.13). These tensors
      share the principal axis normal to the ligand plane (as imposed by the local
      symmetry). The axes in the ligand plane are, however, rotated 50 degrees with
      respect to each other. The orientation of the quadrupole tensor axes correlate
      within 10 degrees with the orientation of the ligand plane following from the X
      ray structure. Copyright 1998 Academic Press.

PMID- 9571106
TI  - Use of a Phase Reference for Field Mapping with Amplitude Images at Low Field
AB  - We present a method to obtain MRI amplitude images that can picture the magnetic
      field due to arbitrary shaped magnetized objects. The method employees the
      gradient recalled echo sequence and two sets of data obtained in separate
      experiments, one of which provides a phase reference image making it possible to
      eliminate the effect of the B0 field inhomogeneities. The final magnitude images
      have a good signal-to-noise even at low fields, and provide qualitative as well
      as quantitative information about the magnetic field produced by the
      ferromagnetic object. As an example the method is applied to study the field
      produced by a small metal piece in a 500-G scanner, and the experimental results
      are compared with numerical simulations. Copyright 1998 Academic Press.

PMID- 9571107
TI  - Automated Processing of Two-Dimensional Correlation Spectra
AB  - An automated scheme is described which locates the centers of cross peaks in two
      dimensional correlation spectra, even under conditions of severe overlap. Double
      quantum-filtered correlation (DQ-COSY) spectra have been investigated, but the
      method is also applicable to TOCSY and NOESY spectra. The search criterion is the
      intrinsic symmetry (or antisymmetry) of cross-peak multiplets. An initial global
      search provides the preliminary information to build up a two-dimensional
      "chemical shift grid." All genuine cross peaks must be centered at intersections
      of this grid, a fact that reduces the extent of the subsequent search program
      enormously. The program recognizes cross peaks by examining the symmetry of
      signals in a test zone centered at a grid intersection. This "symmetry filter"
      employs a "lowest value algorithm" to discriminate against overlapping responses
      from adjacent multiplets. A progressive multiplet subtraction scheme provides
      further suppression of overlap effects. The processed two-dimensional correlation
      spectrum represents cross peaks as points at the chemical shift coordinates, with
      some indication of their relative intensities. Alternatively, the information is
      presented in the form of a correlation table. The authenticity of a given cross
      peak is judged by a set of "confidence criteria" expressed as numerical
      parameters. Experimental results are presented for the 400-MHz double-quantum
      filtered COSY spectrum of 4-androsten-3,17-dione, a case where there is severe
      overlap. Copyright 1998 Academic Press.

PMID- 9571108
TI  - Pore-Structure Determinations of Silica Aerogels by 129Xe NMR Spectroscopy and
      Imaging
AB  - Silica aerogels represent a new class of open-pore materials with pore dimensions
      on a scale of tens of nanometers, and are thus classified as mesoporous
      materials. In this work, we show that the combination of NMR spectroscopy and
      chemical-shift selective magnetic resonance imaging (MRI) can resolve some of the
      important aspects of the structure of silica aerogels. The use of xenon as a
      gaseous probe in combination with spatially resolved NMR techniques is
      demonstrated to be a powerful, new approach for characterizing the average pore
      structure and steady-state spatial distributions of xenon atoms in different
      physicochemical environments. Furthermore, dynamic NMR magnetization transfer
      experiments and pulsed-field gradient (PFG) measurements have been used to
      characterize exchange processes and diffusive motion of xenon in samples at
      equilibrium. In particular, this new NMR approach offers unique information and
      insights into the nanoscopic pore structure and microscopic morphology of
      aerogels and the dynamical behavior of occluded adsorbates. MRI provides
      spatially resolved information on the nature of the flaw regions found in these
      materials. Pseudo-first-order rate constants for magnetization transfer among the
      bulk and occluded xenon phases indicate xenon-exchange rate constants on the
      order of 1 s-1 for specimens having volumes of 0.03 cm3. PFG diffusion
      measurements show evidence of anisotropic diffusion for xenon occluded within
      aerogels, with nominal self-diffusivity coefficients on the order of D = 10(-3)
      cm2/s. Copyright 1998 Academic Press.

PMID- 9571109
TI  - Isotope-Filtered Affinity NMR
AB  - A double-editing pulse sequence has been developed that allows the direct
      observation of protein binding ligand(s) from a mixture of compounds. This
      technique should aid the discovery of lead pharmaceutical compounds. The proton
      NMR signals from protein and the nonbinding ligands are simultaneously eliminated
      using 13C isotope editing and PFG diffusion-edited NMR. This new experiment is
      demonstrated using 13C/15N-labeled stromelysin catalytic domain (SCD). Copyright
      1998 Academic Press.

PMID- 9571110
TI  - Spin Echo Attenuation of Restricted Diffusion as a Discord of Spin Phase
      Structure
AB  - By using the particle probability density we analyze the spin echo attenuation of
      particles, diffusing in a bounded region. It provides a means to expand a
      nonuniform spin phase distribution into a series of waves that characterize the
      geometry and boundary conditions of confinement. Random motion disrupts the
      initial phase structure created by applied gradients and consequently discords
      its structure waves. By assuming the spin phase fluctuation and/or the randomness
      of spin phase distribution in the subensemble as a Gaussian stochastic process,
      we derive a new analytical expression for the echo attenuation related to the
      particle velocity correlation. For a diffusion in porous structure we get the
      expression featuring the same "diffusive diffraction" patterns as those being
      found and explained by P. T. Callaghan and A. Coy ("Principles of Nuclear
      Magnetic Resonance Microscopy," Oxford Univ. Press, Oxford (1991); J. Chem. Phys.
      101, 4599-4609 (1994)) with the use of propagator theory. With the new approach
      we cast a new light on the phenomena and derive analitically how the diffusive
      diffractions appear when the sequence of finite or even modulated gradients are
      applied. The method takes into account the non-Markovian character of restricted
      diffusion, and therefore the echo dependence on the diffusion lengths and on the
      strength of applied gradient differs from the results of authors assuming the
      Markovian diffusion either by dealing with the diffusion propagators or by the
      computer simulation of Fick's diffusion. Copyright 1998 Academic Press.

PMID- 9571111
TI  - Improved Estimation of Protein Rotational Correlation Times from 15N Relaxation
      Measurements
AB  - In the study of protein backbone dynamics by 15N relaxation measurements, an
      initial estimation of the isotropic global correlation time, taum, is usually
      obtained from the average T1/T2 ratio of nuclear spins that do not exhibit slow
      internal motion and with T2 values not significantly shortened by chemical or
      conformational exchange processes. Different methods have been used for
      identification of the rates of internal motion. However, the number of nuclear
      spins included in the taum estimation is often larger than the number that
      ultimately can be fitted to a single-order parameter, S2, implying that some
      nuclear spins involved in the initial taum estimation actually have an effective
      internal correlation time, taue, not as fast as assumed. As a consequence, taum
      is underestimated, since internal motion reduces the T1/T2 ratio. This situation
      becomes more obvious if the molecule has a large taum value because the reduction
      in T1/T2 ratio arising from internal motion is more significant than for
      molecules with smaller taum and the same degree of internal motion. This
      Communication describes a more reliable method for identifying nuclear spins
      which should be excluded from the taum estimation because of insufficiently rapid
      internal motion. This results in an improved taum value, giving a much better
      agreement between the number of nuclear spins fitted successfully to a single
      order parameter, S2, and those used in the taum estimation. Copyright 1998
      Academic Press.

PMID- 9571112
TI  - An Off-resonance Rotating Frame Relaxation Experiment for the Investigation of
      Macromolecular Dynamics Using Adiabatic Rotations
AB  - 15N off-resonance rotating frame relaxation can be applied to the study of
      internal dynamics in proteins in the millisecond to microsecond regime. We show
      that the performance of existing methods can be improved by application of
      simultaneous amplitude and phase-modulated adiabatic RF pulses to align the
      nuclear spin magnetization with the off-resonance spin-lock field for all the
      spins under investigation. Application of this technique to the 269-residue
      serine protease PB92 allowed the measurement of 15N off-resonance rotating frame
      relaxation rates for all nonoverlapping residues in the protein, including the
      arginine side chains, encompassing a chemical shift range of 50 ppm. Simulations
      indicate that by use of the proposed adiabatic RF pulses rotating frame
      relaxation rates can be obtained for magnetization vectors aligned at arbitrary
      angles with the static field. Copyright 1998 Academic Press.

PMID- 9571113
TI  - Measurement of Chemical Exchange Rate Constants with Solvent Protons Using
      Radiation Damping
AB  - When chemical exchange occurs between a concentrated and a diluted species like
      the proton exchange between water and proteins in biochemical systems, it is
      difficult to use the conventional methods for a quantitative dynamical study. In
      this paper, a new approach which utilizes radiation damping of the strong water
      magnetization exchanging with the weak resonance of the mobile protons in
      biomolecules is proposed. It is demonstrated with a dilute guanidine solution,
      using the simple inversion-recovery pulse sequence, that the exchange rate
      constants between water and guanidine protons are evaluated by solving the Bloch
      equations modified with both the radiation damping and the chemical exchange
      effects. Copyright 1998 Academic Press.

PMID- 9571114
TI  - Internet Technology in Magnetic Resonance: A Common Gateway Interface Program for
      the World-Wide Web NMR Spectrometer
AB  - A custom-written Common Gateway Interface (CGI) program for remote control of an
      NMR spectrometer using a World Wide Web browser has been described. The program,
      running on a UNIX workstation, uses multiple processes to handle concurrent tasks
      of interacting with the user and with the spectrometer. The program's parent
      process communicates with the browser and sends out commands to the spectrometer;
      the child process is mainly responsible for data acquisition. Communication
      between the processes is via the shared memory mechanism. The WWW pages that have
      been developed for the system make use of the frames feature of web browsers. The
      CGI program provides an intuitive user interface to the NMR spectrometer, making,
      in effect, a complex system an easy-to-use Web appliance. Copyright 1998 Academic
      Press.

PMID- 9571115
TI  - Paramagnetic Inversion of the Sign of the Interference Contribution to the
      Transverse Relaxation of the Imido Protons of the Coordinated Imidazoles in the
      Uniformly 15N-Labeled Cytochrome c3
AB  - In the spectrum of uniformly 15N-labeled cytochrome c3, the relative linewidths
      of the doublet peaks of the 15N-coupled imido proton of the coordinated imidazole
      group were reversed on oxidation. This inversion was explained by the
      interference relaxation process between the electron-proton dipolar and 15N-1H
      dipolar interactions. The inversion can be used to assign the imido protons of
      the coordinated imidazole groups in heme proteins. Copyright 1998 Academic Press.

PMID- 9571116
TI  - Measurement of J and dipolar couplings from simplified two-dimensional NMR
      spectra.
AB  - Simple procedures are described for recording complementary in-phase and
      antiphase J-coupled NMR spectra. The sum and difference of these spectra contain
      only the upfield and the downfield components of a doublet, making it possible to
      measure the J splitting directly from these combinations without an increase in
      resonance overlap relative to the decoupled spectrum. The approach is
      demonstrated for measurement of 1JNH splittings and 2JHNC splittings in oriented
      and isotropic ubiquitin. Dipolar couplings obtained from differences in the
      splittings measured in the oriented and isotropic phases are in excellent
      agreement with dipolar couplings obtained from direct measurement of the
      splitting or from a conventional E. COSY-type measurement.

PMID- 9571117
TI  - MEETINGS CALENDAR
AB  - Copyright

PMID- 9571118
TI  - Hyperfine Structure of Rotation-Inversion Levels in the Excited nu2 State of
      Ammonia
AB  - Hyperfine structures of the rotation-inversion transitions with J = 3 <-- 2, s <-
      a, and K = 0, 1, 2, and with J = 0 <-- 1, a <-- s, and K = 0 in the excited nu2
      vibrational state have been resolved and measured by sub-Doppler saturation
      spectroscopy using the Cologne terahertz spectrometer with an accuracy of about 1
      kHz. The line frequencies of the hyperfine structures of the rotation inversion
      transitions (at 466, 769, 742, and 763 GHz) have been simultaneously analyzed
      with the previously published J = 2 <-- 1, s <-- a, K = 1, nu2 transition in
      terms of effective nuclear quadrupole and spin-rotation parameters. The
      corresponding pure rotation-inversion frequencies, deperturbed from the hyperfine
      effects, have also been derived. Copyright 1998 Academic Press.

PMID- 9571119
TI  - High Resolution FTIR Study of the nu5 Bands of HSiD3 and H120SnD3
AB  - High resolution Fourier Transform spectra of HSiD3 and monoisotopic H120SnD3 have
      been recorded in the region of the nu5 fundamental at 850.68 and 646.90 cm-1 with
      a resolution of 3.3 and 2.8 x 10(-3) cm-1, respectively. About 2000 rovibrational
      transitions of each species have been assigned and fitted to two different
      reductions of the effective Hamiltonian, with sigma(Fit) = 1.2 x 10(-4) (HSiD3)
      and 1.4 x 10(-4) cm-1 (H120SnD3). The two sets of parameters were shown to be
      equivalent, and relations between parameters belonging to different reductions
      are perfectly fulfilled. Furthermore the ground state constants C0 and DK0 have
      been determined for the first time. For consistency the previously measured data
      belonging to the nu5 band of H70GeD3 have been refitted, sigma(Fit) = 1.6 x 10(
      4) cm-1, on the basis of improved ground state parameters including the h'3 term
      accounting for the splitting of the K = 3 level. Copyright 1998 Academic Press.

PMID- 9571121
TI  - Joint Rotational Analysis of 24 Bands of the H2Se Molecule
AB  - A global fit of all currently available rotation-vibration energies has been made
      for 24 vibrational states of the H802Se molecule. The resulting set of 112
      parameters reproduces the initial 3516 vibration-rotation energies with a mean
      accuracy of 10.6 x 10(-3) cm-1. Using this model as a starting point, the
      rotational fine structure of the extremely weak local mode bands (13(+); 1)/(13(
      ); 1) and (06(+); 0)/(06(-); 0) could be analyzed; the results are discussed.
      Copyright 1998 Academic Press.

PMID- 9571120
TI  - Expressions of Effective Hamiltonian Parameters of XY4 Molecules in the
      Tetrahedral Formalism
AB  - We have derived expressions of second-order effective Hamiltonian parameters of
      XY4 molecules in the tetrahedral formalism (1992, J. P. Champion et al.,
      "Spectroscopy of the Earth's Atmosphere and Interstellar Medium: Spherical Top
      Spectra," Academic Press, San Diego). They are written as a function of the force
      constants of the potential expanded in terms of the dimensionless normal
      coordinates. These expressions can be used in the isolated band scheme as well as
      in the polyad one. The ambiguity of the effective Hamiltonian parameters is
      treated. Relations between the parameters for q2 and q4 terms and Hecht's
      anharmonicity constants (1960, K. T. Hecht, J. Mol. Spectrosc. 5, 355-389) in the
      isolated band scheme are established. Copyright 1998 Academic Press.

PMID- 9571122
TI  - 14N Hyperfine Structure in the Pure Rotational Spectrum of 24Mg14N12C
AB  - The pure rotational spectrum of 24Mg14N12C, between 11.9 and 23.9 GHz, has been
      measured using a pulsed jet Fourier transform microwave spectrometer. The
      hyperfine structure due to the 14N nucleus has been measured, and the nuclear
      quadrupole coupling, Fermi contact, and dipole-dipole interaction constants have
      been determined. The ionic character of the metal-isocyanide bond has been
      investigated through the nuclear quadrupole and magnetic hyperfine parameters.
      Copyright 1998 Academic Press.

PMID- 9571123
TI  - Rotational Analysis of the 210 and 220 Bands of the a 3B1 <-- &Xtilde; 1A1 System
      of Jet-Cooled Silicon Difluoride
AB  - A combination least-squares and band contour analysis of the 2(1)0 and 2(2)0
      bands of the laser-induced phosphorescence spectrum of the a 3B1 <-- &Xtilde; 1A1
      band system silicon difluoride, SiF2, has been completed. Spectra were taken
      under pyrolysis-jet conditions at a resolution of ca 0.04 cm-1. The rotational
      (A, B, C), centrifugal distortion (Deltak), spin-rotation (a, a0), and spin-spin
      (alpha, beta) constants for the upper nu2 state are reported. An effective r0
      structure has been calculated for each upper vibronic state. Some minor intensity
      anomalies have been observed in the spectra of both bands. Copyright 1998
      Academic Press.

PMID- 9571124
TI  - Line Intensities for the 8-um Bands of SO2
AB  - Using both high-resolution (R = 0.003 cm-1) and medium-resolution (R = 0.12 cm-1)
      Fourier transform spectroscopy, it has been possible to measure accurately a
      large set of individual line intensities for the nu1 and nu3 bands of SO2 in the
      950-1400 cm-1 spectral region. These intensities were introduced into a least
      squares fit calculation allowing one to obtain the expansion of the transition
      moment operator of the nu1 and nu3 bands. For these intensity calculations, the
      theoretical model takes into account the vibration-rotation interactions linking
      the upper levels involved in the nu1, 2nu2, and nu3 interacting SO2 bands.
      Finally, a synthetic spectrum of the 8-um SO2 bands has been generated using the
      dipole moment expansion determined in this work and the molecular parameters and
      the Hamiltonian matrix given in a previous analysis. Copyright 1998 Academic
      Press.

PMID- 9571125
TI  - Subdoppler Study of the nu7 Band of C2H4 with a CO2 Laser Sideband Spectrometer
AB  - The saturation spectrum of ethylene has been studied between 900 and 1100 cm-1
      with the sub-Doppler sideband spectrometer of Lille. Two hundred absorption lines
      have been recorded with an absolute accuracy of approximately 15 kHz. On the
      basis of these accurate data, a new global analysis of the GS and of the nu7,
      nu10, and nu4 upper states was achieved taking into account the Coriolis
      interactions up to the third order. A statistical agreement is obtained with all
      experimental data with an estimated standard deviation equal to 0.825. The
      spectra of ethylene between 900 and 1100 cm-1 become very good wavenumber
      standards with an absolute accuracy of 10(-6) cm-1. Copyright 1998 Academic
      Press.

PMID- 9571126
TI  - High-Resolution Fourier Transform Spectra of HDS in the Regions of the Bands nu1
      and 2nu1/nu2 + nu3
AB  - High-resolution spectrum of the HDS molecule was recorded with the Bruker Fourier
      spectrometer in Oulu in the regions of the nu1 and 2nu1/nu2 + nu3 absorption
      bands. Fine rotational structure of the nu1 band was analyzed with the model of
      an isolated vibrational state, while in the analysis of the 2nu1 and nu2 + nu3
      bands it was necessary to take into account the resonance interactions between
      these two bands. Comparison of the experimentally determined parameters is made
      with the deductions of the expanded local mode approach. Copyright 1998 Academic
      Press.

PMID- 9571127
TI  - A Study of the X 2Sigma+ and A 2Pi States of SiO+ Using Fast-Ion-Beam Laser
      Spectroscopy
AB  - We have observed for the first time the (4, 4), (4, 3), and (5, 4) bands of the B
      2Sigma+-X 2Sigma+ system of SiO+ using laser-induced fluorescence spectroscopy on
      a fast SiO+ beam. These data contain avoided crossings between the X 2Sigma+ and
      A 2Pi states, as well as a few extra lines belonging to the (3, 2), (4, 2), and
      (5, 3) bands of the B 2Sigma+-A 2Pi system. They enlarge considerably a
      previously measured data set consisting of almost 1400 lines of the (0, 0), (1,
      1), (2, 2), (3, 3), (1, 0), (2, 1), and (3, 2) bands of the B-X system and 66
      lines of the (2, 0) Omega = (1/2) subband of the B 2Sigma+-A 2Pi system. The
      entire data set of 2378 assigned lines has been fit simultaneously to a model
      Hamiltonian in which many closely overlapped levels of the X and A states are
      handled by direct diagonalization. The newly observed avoided crossings between
      the X and A states allow the determination of many A-state parameters with
      increased precision, several for the first time, including the spin-orbit
      splitting. The analysis confirms our earlier reinterpretation of older
      photoelectron spectroscopy data and allows the accurate prediction of the
      frequencies of strong infrared transitions between the X and A states, which have
      astrophysical significance. Copyright 1998 Academic Press.

PMID- 9571128
TI  - New Rydberg-Rydberg Transitions of the ArH and ArD Molecules
AB  - We report and rotationally analyze new spectra of the ArH and ArD molecules
      corresponding to the 0-0 vibrational bands of electronic transitions from the nd
      and ns states to the 4p Rydberg complex, in united atom notation. In ArD, our
      observation of the 3ddelta state, along with previous observations of the 3dpi
      and 3dsigma states, demonstrates that the components of the 3d state are widely
      separated and can be treated as Hund's case (b) states, unlike the components of
      the np and 4f states, which form closely coupled case (d) Rydberg complexes. The
      band 4dsigma --> 4p has also been assigned. The 4dpi component is known from
      previous work of Lipson, but as yet the 4ddelta component is unknown. Emission
      from the 6s and 8s states is also analyzed. From the intensities in the
      rotational structure, there is evidence that the 6s state interacts with the
      3dsigma state. In ArH, we analyze the 0-0 bands of the 3dpi --> 4p, 3ddelta -->
      4p, 4dsigma --> 4p, and 6s --> 4p transitions. Unlike the rotational levels of
      the 5s state, which are heavily broadened by predissociation, the 4p levels of
      ArH are sharp, so we can perform a more accurate and detailed analysis for this
      isotope than was possible previously. Qualitative features of the ArH spectra
      essentially mirror those of ArD, except that emission from the 3dsigma state was
      not identified, possibly due to a perturbation particular to this isotope.
      Copyright 1998 Academic Press.

PMID- 9571129
TI  - New Rydberg-Rydberg Transitions of the ArH and ArD Molecules
AB  - We report observations and analyses of bands in the spectra of the ArH and ArD
      molecules due to emission from the 4f Rydberg complexes. For ArD, the observed
      bands are 4f --> 5s and 4f --> 3dlambda for all three components lambda = 0, 1,
      and 2 of the 3d state. These give direct information on all 14 spin-orbit
      components of the 4f complex. For ArH, the data is more limited because the
      levels of the 5s state are broadened by predissociation, and only the lambda = 2
      component of the 4f --> 3dlambda transitions is seen clearly, although a number
      of lines could be assigned to the 4f --> 3dpi band, which is strongly overlapped
      by the 6s --> 4p band. The 4f complexes of both isotopes are good example of
      Hund's case (d) coupling. The 4f orbitals are essentially non-core-penetrating,
      so that spin-orbit coupling is negligible for them, and the zero-rotation
      splitting agrees well with calculations from the ab initio quadrupole moment and
      anisotropic polarizability of the core. The orbit-rotation coupling parameter
      xi4f gives a value of the core electric dipole moment that is in reasonable
      agreement with ab initio and previous experimental values. A summary of the
      presently known states of ArH and ArD is presented. Copyright 1998 Academic
      Press.

PMID- 9571130
TI  - Correlated and Noncorrelated Lineshape Models under Small Lineshift Condition:
      Analysis of Self-Perturbed CH3D
AB  - The 14 transitions belonging to the P branch of the nu3 band of CH3D, near 1250
      cm-1, have been measured with a tunable diode-laser spectrometer. These lines,
      recorded at a total pressure ranging from 1 to 60 mbar, have been analyzed by
      means of soft and hard collision lineshape models. We emphasize the equivalence
      between the correlated and noncorrelated profiles, when the collisional lineshift
      may be neglected. As a result, new measurements of linestrengths, collisional
      self-broadening coefficients, and other parameters related to the Dicke effect
      are provided at room temperature. It is also shown that the instrumental
      distortions must be properly taken into account to avoid systematic errors on the
      fitted lineshape parameters, especially at low pressure. The broadening
      coefficients are compared with results calculated from a semiclassical theory,
      performed by considering, in addition to electrostatic interactions involving the
      octopole and hexadecapole moments of CH3D, the dispersion contributions.
      Copyright 1998 Academic Press.

PMID- 9571132
TI  - Cerebral processes related to visuomotor imagery and generation of simple finger
      movements studied with positron emission tomography.
AB  - Positron emission tomography was used to compare the functional anatomy of visual
      imagination and generation of movement. Subjects were asked to generate visual
      images of their finger movement in response to a preparatory signal. Four
      conditions were tested: in two, no actual movement was required; in the other
      two, a second signal prompted the subjects to execute the imagined movement.
      Which movement to imagine was either specified by the preparatory stimulus or
      freely selected by the subjects. Compared with a rest condition, tasks involving
      only imagination activated several cortical regions (inferoparietal cortex,
      presupplementary motor area, anterior cingulate cortex, premotor cortex,
      dorsolateral prefrontal cortex) contralateral to the imagined movement. Tasks
      involving both imagination and movement additionally increased activity in the
      ipsilateral cerebellum, thalamus, contralateral anteroparietal, and motor cortex
      and decreased activity in the inferior frontal cortex. These results support the
      hypothesis that distinct functional systems are involved in visuomotor
      imagination and generation of simple finger movements: associative parietofrontal
      areas are primarily related to visuomotor imagination, with inferior frontal
      cortex likely engaged in active motor suppression, and primary motor structures
      contribute mainly to movement execution.

PMID- 9571133
TI  - Nucleotide sequence and genetic characterization of the novel IncQ-like plasmid
      pIE1107.
AB  - The analysis of the complete nucleotide sequence of the small resistance plasmid
      pIE1107 revealed a close similarity to the well-known IncQ plasmids. Highly
      conserved replication proteins and nearly identical origins of replication (oriV)
      suggest equivalent functions in the related replication systems. However, pIE1107
      contains two copies of IncQ-oriV-like DNA which are slightly different regarding
      the iterons. Upon deletion of a silent copy of IncQ-oriV-like DNA the resulting
      plasmid is fully compatible with IncQ plasmids, indicating that there is no
      mutual communication between the replication control of the respective replicons.
      Experiments with cloned oriV DNA strongly suggest that the replication initiation
      protein of pIE1107 has specialized into the distinct target-iterons of its own
      oriV which differs only by a few nucleotides from the oriV of IncQ plasmids.
      Implications from the apparent highly specific protein-DNA recognition and from
      the incompatibility properties of pIE1107 for the evolution of a family of
      compatible, IncQ-like plasmids are discussed.

PMID- 9571134
TI  - Conjugal transfer of plasmid DNA from Escherichia coli to enterococci: a method
      to make insertion mutations.
AB  - Shuttle vector pAT18 was transferred by conjugation from Escherichia coli S17-1
      to Enterococcus faecalis OG1RF and Enterococcus faecium SE34. Transfer was
      mediated by the transfer functions of plasmid RK2 in E. coli S17-1 and the origin
      of conjugal transfer (oriT) located on pAT18. The oriT sequence was then inserted
      into two plasmids to generate vectors pTEX5235 and pTEX5236. These two vectors
      cannot replicate in gram-positive bacteria and can be used to make insertion
      mutants in gram-positive bacteria. An internal sequence from an autolysin gene of
      E. faecalis OG1RF was cloned into pTEX5235 and transferred by conjugation from E.
      coli S17-1 to E. faecalis OG1RF. The plasmid was found to integrate into the
      chromosome of OG1RF by a single crossover event, resulting in a disrupted
      autolysin gene. A cosmid carrying the pyrimidine gene cluster from E. faecalis,
      with a transposon insertion in pyrC, was also transferred from E. coli S17-1 to
      E. faecalis OG1RF. After selection for the transposon, it was found to have
      recombined into the recipient chromosome by a double crossover between the cosmid
      and the chromosome of OG1RF. This resulted in a pyrC knockout mutant showing an
      auxotrophic phenotype.

PMID- 9571135
TI  - IS1491 from Pseudomonas alcaligenes NCIB 9867: characterization and distribution
      among Pseudomonas species.
AB  - A new insertion sequence, IS1491, has been cloned and sequenced. The 2489-bp
      IS1491 was isolated from a Pseudomonas alcaligenes NCIB 9867 (strain P25X) 4.8-kb
      PstI chromosomal fragment. IS1491 is flanked by an imperfect inverted repeat of
      23 bp and carries two overlapping open reading frames, ORF1 and ORF2. Both ORF1
      and ORF2 displayed homology to the IstA-like and IstB-like transposases encoded
      by the IS21 family of insertion sequences, which include two IS elements
      previously isolated from P. alcaligenes P25X, IS1474, and IS1475 (Yeo, C. C., and
      Poh, C. L. (1997). FEMS Microbiol. Lett. 149, 257-263). Transposition assays
      showed that IS1491 transposed at a frequency of approximately 1.4 x 10(-6).
      Transposition of IS1491 into the target pRK415 replicon was observed but when
      ORF2 was disrupted, a fusion between the donor and target replicons was detected.
      IS1491-like sequences were detected in total DNA of Pseudomonas putida NCIB 9869
      (strain P35X), Pseudomonas aeruginosa, Pseudomonas stutzeri, Pseudomonas
      syringae, Pseudomonas mendocina, Comomonas acidovorans, and Comomonas
      testosteroni by hybridization with IS1491 DNA.

PMID- 9571136
TI  - Isolation and characterization of IS1416 from Pseudomonas glumae, a new member of
      the IS3 family.
AB  - Isolation and characterization of four different insertion sequence (IS) elements
      from Pseudomonas glumae MAFF 302744 through transposition into the entrapment
      vector pSHI1063 are described. One of the elements, IS1416, was further
      characterized. IS1416 is 1322 bp long and carries 29-bp terminal inverted repeats
      flanked by a 3-bp direct duplication. IS1416 contains three open reading frames
      (ORFs), which are designated ORFA1, ORFA2, and ORFB, on one strand. Both DNA
      sequence of IS1416 and the deduced amino acid sequences of its ORFs strongly
      suggest that IS1416 is a member of the IS3 family, and is closely related to
      IS401 from Pseudomonas cepacia and IS51 from Pseudomonas syringae. To our
      knowledge, IS1416 is the first IS element isolated from P. glumae. The gene
      organization and possible regulation of transposition functions of IS1416 are
      also discussed.

PMID- 9571137
TI  - pTn5cat: a Tn5-derived genetic element to facilitate insertion mutagenesis,
      promoter probing, physical mapping, cloning, and marker exchange in
      phytopathogenic and other gram-negative bacteria.
AB  - A Tn5-derived mobile element has been constructed to identify genes and promoters
      related to pathogenesis and virulence in Pseudomonas syringae pv. phaseolicola.
      To enhance the rate of mutation this Tn5 derivative was constructed carrying a
      mutant transposase which was placed in cis to the transposable element, but just
      outside the inverted repeats, therefore eliminating secondary transposition and
      increasing the stability of the insertion. The new element also contains a
      promoterless cat (chloramphenicol acetyltransferase) gene as reporter to allow
      for positive selection of promoters being expressed under specific conditions. To
      facilitate cloning and manipulations in Escherichia coli, a ColE1 origin of
      replication has been included within the transposable element as well as the Mob
      region from the broad-host-range plasmid RP4, which allows this element to be
      efficiently mobilized by a triparental mating or by using an E. coli strain such
      as S17-1 to provide the tra functions. Sites for the rare cutters PacI and PmeI
      have also been included to facilitate locating the insertions on a PacI and/or
      PmeI physical map. This construction combines the properties of both a
      mobilizable plasmid and a transposon and therefore has been termed pTn5cat. It is
      almost the same size as the wild-type Tn5, 5877 bp, and has successfully been
      tested in P.s. phaseolicola and Xanthomonas campestris pv. campestris.

PMID- 9571139
TI  - Plasmid-mediated histamine biosynthesis in the bacterial fish pathogen Vibrio
      anguillarum.
AB  - Histamine production in bacteria-contaminated fish is the result of the presence
      of bacterial histidine decarboxylase activity, which converts histidine present
      in muscle proteins to histamine. The fish pathogen Vibrio anguillarum harbors a
      plasmid-encoded histidine decarboxylase gene (angH) that is essential for
      biosynthesis of the siderophore anguibactin. However, the role of angH in
      histamine biosynthesis by this pathogen has not been fully determined. Thus, the
      objectives of this study were to monitor the production and release of histamine
      by the wild-type as well as by a plasmidless strain and angH isogenic mutants
      generated by allelic exchange. Reverse transcription polymerase chain reaction
      showed that only the wild-type strain expressed angH, while no angH message was
      detected in the mutants and the plasmidless derivative. The iron uptake-deficient
      phenotype of one of the angH mutants confirmed the location of the mutation and
      the unique role of this gene in iron acquisition. Thin-layer chromatography, gas
      chromatography, and mass spectrometry showed that histamine was released by the
      strain harboring a wild-type angH gene when grown in excess histidine. This
      biogenic amine was not detected in the culture supernatants of the plasmidless
      derivative and the angH mutant when cultured under the same experimental
      conditions. These results indicate that angH is essential for histamine
      biosynthesis in V. anguillarum, a compound responsible for food poisoning and
      potentially involved in bacterial virulence. Thin-layer chromatography of wild
      type culture supernatants and beta-galactosidase assays using the isogenic angH
      mutant demonstrated that the expression of this gene is independent of the
      histidine concentration of the medium under both iron-rich and iron-limiting
      conditions.

PMID- 9571138
TI  - Requirements for rapid plasmid ColE1 copy number adjustments: a mathematical
      model of inhibition modes and RNA turnover rates.
AB  - The random distribution of ColE1 plasmids between the daughter cells at cell
      division introduces large copy number variations. Statistic variation associated
      with limited copy number in single cells also causes fluctuations to emerge
      spontaneously during the cell cycle. Efficient replication control out of steady
      state is therefore important to tame such stochastic effects of small numbers. In
      the present model, the dynamic features of copy number control are divided into
      two parts: first, how sharply the replication frequency per plasmid responds to
      changes in the concentration of the plasmid-coded inhibitor, RNA I, and second,
      how tightly RNA I and plasmid concentrations are coupled. Single (hyperbolic)-
      and multiple (exponential)-step inhibition mechanisms are compared out of steady
      state and it is shown how the response in replication frequency depends on the
      mode of inhibition. For both mechanisms, sensitivity of inhibition is "bought" at
      the expense of a rapid turnover of a replication preprimer, RNA II. Conventional,
      single-step, inhibition kinetics gives a sloppy replication control even at high
      RNA II turnover rates, whereas multiple-step inhibition has the potential of
      working with unlimited precision. When plasmid concentration changes rapidly, RNA
      I must be degraded rapidly to be "up to date" with the change. Adjustment to
      steady state is drastically impaired when the turnover rate constants of RNA I
      decrease below certain thresholds, but is basically unaffected for a
      corresponding increase. Several features of copy number control that are shown to
      be crucial for the understanding of ColE1-type plasmids still remain to be
      experimentally characterized. It is shown how steady-state properties reflect
      dynamics at the heart of regulation and therefore can be used to discriminate
      between fundamentally different copy number control mechanisms. The experimental
      tests of the predictions made require carefully planned assays, and some
      suggestions for suitable experiments arise naturally from the present work. It is
      also discussed how the presence of the Rom protein may affect dynamic qualities
      of copy number control.

PMID- 9571141
TI  - In Memoriam: Mette Strand
AB  - Copyright

PMID- 9571140
TI  - Eukaryotic expression vectors that replicate to low copy number in bacteria:
      transient expression of the Menkes protein.
AB  - A set of low copy number plasmid vectors for mammalian gene expression has been
      constructed. These vectors are derived from the previously described bacterial
      low copy number expression vectors, pWSK29 and pWKS30, which are present at six
      to eight copies per cell. The new plasmids also have the following useful
      properties: (1) they contain antibiotic resistance markers for the selection of
      stable mammalian cell lines; (2) they have either constitutive or inducible
      promoters; (3) a chimeric intron, for enhancing gene expression, is present; (4)
      they contain unique cloning sites; (5) they have an SV40 polyadenylation signal,
      and a subset of the vectors have an SV40 origin of replication for episomal
      replication and transient gene expression. A cDNA encoding the Menkes disease
      protein was cloned into two of these vectors, and transient expression studies in
      COS-7 cells showed that both constitutive and inducible expression was possible.
      This set of expression vectors will provide a useful tool for the manipulation,
      in Escherichia coli, of mammalian genes or cDNAs that are unstable in the high
      copy number vectors that are currently available.

PMID- 9571142
TI  - Trypanosoma cruzi: optimization of polymerase chain reaction for detection in
      human blood.
AB  - We have optimized the conditions for DNA extraction and polymerase chain reaction
      (PCR) amplification to diagnose the presence of Trypanosoma cruzi DNA in the
      blood and serum of patients with chronic Chagas disease. The approximately 330-bp
      fragment of the kinetoplast minicircles was used as a target for amplification.
      The use of chemiluminescence on slot blots with a specific alkaline phosphatase
      conjugated oligonucleotide probe detected specific product from as little as 0.1
      fg of T. cruzi kDNA. An additional product of approximately 200 bp inadvertently
      amplified from the human genome was observed in human blood from T. cruzi
      negative and -positive samples and served as an internal control of the
      amplification. Samples from other mammalian hosts were also assayed using the PCR
      protocol. The higher sensitivity of our PCR method observed in both acute and
      chronic phases of T.cruzi infections in mice and dog, respectively, could be
      useful in monitoring the course of infection during experimental drug tests in
      laboratory animals. Since this procedure showed a higher sensitivity than other
      protocols in the literature, it may be a suitable routine test in diagnosing
      Chagas disease, especially for patients presenting very low parasitemia levels.

PMID- 9571143
TI  - Structure and physiology of calpain, an enigmatic protease.
AB  - Calpain is one of the most extensively studied proteinases (1). Although its
      enzymatic and structural properties have been well characterized, neither the
      structure-function relationship nor physiological functions are completely
      understood. In recent years, increasing numbers of molecules showing sequence
      similarity to calpain have been identified and the concept of a "calpain super
      family" has become general (2, 3). The term "calpain" originally meant a Ca(2+)
      activated, neutral, and intracellular cysteine proteinase, although a proteinase
      domain similar to that of calpain is a prerequisite for a member of the "calpain
      super family" (4, 5). The molecular diversity of calpain has attracted interest
      to its structural and functional transition during evolution. Here we describe
      the state of current knowledge, progress, and clues to the next phase of calpain
      research.

PMID- 9571144
TI  - Analysis of translation elongation factors from wheat during development and
      following heat shock.
AB  - Translational activity in plants undergoes rapid changes during developmental
      stages such as seed formation and germination, and during abiotic stresses such
      as heat shock, hypoxia and wounding. We examined the protein levels and
      isoelectric state of two components of the translation machinery, elongation
      factor (EF) 1 alpha and 2, to determine their roles in the regulation of
      translation. We found that the apparent protein levels of EF1 alpha increase
      relative to the EF2 levels which decline slightly during the development of the
      wheat seed. During germination, high levels of these factors are present in
      seedling tissues known to be actively engaged in translation; however, no
      differences in isoelectric state were observed during germination. As an example
      of abiotic stress, heat shock had little impact on the apparent levels of EF1
      alpha or EF2 present in wheat leaves, nor were changes in the number or levels of
      isoforms observed.

PMID- 9571145
TI  - Evidence for a physiological role of NH4+ transport on the secretory Na(+)-K(+)
      2Cl- cotransporter.
AB  - The secretory Na(+)-K(+)-2Cl- cotransporter in salivary acinar cells is
      responsible for driving the transepithelial Cl- fluxes that give rise to fluid
      secretion. We demonstrate that the application of the muscarinic agonist
      carbachol to rat parotid acini results in an intracellular acid load that can be
      blocked by bumetanide, a specific inhibitor of the cotransporter. One component
      of this bumetanide-sensitive acid load is ouabain-sensitive while a second is
      dependent on the presence of sub-millimolar concentrations of NH4+ in our media.
      Our data indicate that this latter effect arises from NH4+ entry on the
      cotransporter operating in a Na(+)-NH4(+)-2Cl- cotransport mode and that at
      physiological NH4+ levels in the rat (approximately 0.1 mM), 10-15% of the acinar
      Cl- entry occurs via this route. We suggest that Na(+)-NH4(+)-2Cl- cotransport
      may also play a significant physiological role in other cell types and that this
      mode of operation of the secretory Na(+)-K(+)-2Cl- cotransporter could account
      for the currently unexplained presence of this protein in a number of tissues.

PMID- 9571146
TI  - Fluvastatin enhances receptor-stimulated intracellular Ca2+ release in human
      keratinocytes.
AB  - We analyzed the effect of isoprenoid depletion by fluvastatin on bradykinin (BK)-
      and epidermal growth factor (EGF)-mediated Ca2+ mobilization and prostaglandin E2
      production, in the human keratinocyte cell line HaCaT. BK and EGF stimulated Ca2+
      mobilization in an agonist-dependent manner. The synthesis of prostaglandin E2
      paralleled the level of Ca2+ mobilization induced by BK and EGF. Treatment with
      fluvastatin increased the EGF-promoted but not the BK-promoted Ca2+ mobilization
      and prostaglandin E2 production in Ca(2+)-containing medium. In the absence of
      extracellular Ca2+, fluvastatin treatment led to an increase in intracellular
      Ca2+ release by both agonists. This effect was abolished by depleting the
      intracellular pool of Ca2+ with thapsigargin. Our findings showed that the
      intracellular Ca2+ release was dependent on the metabolism of mevalonate and that
      the Ca2+ mobilization modulated prostaglandin E2 synthesis in human
      keratinocytes.

PMID- 9571147
TI  - Sequence analysis and expression of the filamentous phage phi Lf gene I encoding
      a 48-kDa protein associated with host cell membrane.
AB  - One viral strand of phi Lf, a filamentous phage of Xanthomonas campestris
      pv.campestris, the open reading frame (ORF440) behind gene VI was identified as
      gene I. This gene codes for pI protein (440 aa, 48 kDa) which was shown to be
      membrane-bound in the phi Lf-infected host cell by Western blot analysis using
      the antibody raised against the protein expressed in Escherichia coli. Its
      predicted amino acid sequence has a nucleotide-binding motif in the N-terminal 97
      aa and a membrane-spanning domain (aa 221 to 236). These structural features are
      characteristic of pIs of several filamentous phages which are transmembrane
      proteins required for phage assembly. Thus far, nine phi Lf genes have been
      identified which are organized in the order GII-gX-gV-gVII-gIX-gVIII-gIII-gVI-gI,
      similar to the genome organization of E. coli filamentous phages.

PMID- 9571148
TI  - In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by
      antisense inhibition of the RAD51 gene.
AB  - The mammalian RAD51 gene is a homologue of the yeast RAD51 and E. coli RecA
      genes, which are related to the repair of DNA double-strand breaks and are also
      involved in recombination repair and various SOS responses to DNA damage by gamma
      irradiation and alkylating reagents. In this study, we investigated both in vitro
      and in vivo whether inhibition of the RAD51 gene by antisense oligonucleotides
      (ODNs) enhances the radiosensitivity of mouse malignant gliomas. A volume of 100
      nM of RAD51 antisense ODNs inhibited the level of mRNA by more than 95% and
      reduced the protein expression by about 70%. Treatment of mouse 203G glioma cells
      with 100 nM of RAD51 antisense ODNs significantly enhanced the radiation-induced
      cell kill compared to control cells, and cells treated with sense or scrambled
      ODNs. When the glioma cells were implanted in the cisterna magna of mice followed
      by treatment with RAD51 antisense ODNs, the survival time of the mice was
      markedly prolonged compared to that of the untreated group (p < 0.001, logrank
      test). In addition, the combination of antisense ODNs and irradiation extended
      the survival time of the glioma-bearing mice much longer than could be achieved
      with radiation alone (p < 0.0001, logrank test). These results suggest that
      inhibition of RAD51 can be expected to serve as a novel potentiator for radiation
      therapy in malignant gliomas by inhibiting DNA double-strand break repair.

PMID- 9571149
TI  - Sequence analysis and functional characterization of the 5'-flanking region of
      the rat multidrug resistance protein 2 (mrp2) gene.
AB  - Gene expression of the canalicular conjugate transporter mrp2 is inducible by
      treatment with the DNA-damaging agents 2-acetylaminofluorene (50 and 100 microM),
      and cisplatin (20 microM) in primary rat hepatocytes as well as in the rat
      hepatoma cell line H4IIE. Furthermore, phenobarbital (1 and 2 mM) induces mrp2
      gene expression, probably explaining the increase in bile-salt-independent bile
      flow caused by phenobarbital, while the cholestatic drug ethinyl estradiol (10(
      6) M) leads to an increase in mrp2 mRNA but decreases Mrp2 protein level probably
      via a posttranscriptional mechanism. The 5'-flanking region of the rat mrp2 gene
      was sequenced and cloned into a luciferase reporter vector. Transient
      transfection assays with reporter vectors containing unidirectionally deleted 5'
      flanking regions using H4IIE cells indicate that two different sequences of 17
      and 37 bases comprising a Y-Box and a GC-Box are required for mrp2 gene basal
      expression. Sequences mediating 2-AAF induction are located within a region 250
      bases upstream of the translation start site while the inducing effect of
      phenobarbital seems to be mediated by another domain located further upstream.

PMID- 9571150
TI  - The two phases of regulated exocytosis in permeabilized pancreatic acini are
      modulated differently by heterotrimeric G-proteins.
AB  - In this study we examined the influence on AlF4- and GTP gamma S on amylase
      secretion from alpha toxin permeabilized pancreatic acini. AlF4- only activates
      heterotrimeric G-proteins, whereas GTP gamma S activates both small ras-like GTP
      binding proteins and heterotrimeric G-proteins (Kahn, R. A., J. Biol. Chem., 266,
      15595-15597, 1991). GTP gamma S, but not AlF4-, significantly stimulated Ca2(+)
      independent amylase secretion, suggesting that a small GTP-binding protein
      controls regulated exocytosis distal to the site of action of Ca2+. In contrast,
      both AlF4- and GTP gamma S modulated Ca(2+)-dependent amylase secretion. AlF4-
      and GTP gamma S stimulated the initial rapid, ATP-independent, phase of Ca(2+)
      dependent secretion but inhibited the second slower sustained, ATP-dependent,
      phase of release. There were significant differences in the GTP gamma S
      requirements for the stimulation and inhibition of Ca(2+)-dependent amylase
      secretion, consistent with GTP gamma S activating separate heterotrimeric G
      proteins to modulate each phase of the Ca(2+)-dependent secretory response. Our
      studies also indicated that neither G-protein is a member of the Gi/o class of
      heterotrimeric G-proteins.

PMID- 9571151
TI  - Identification and characterization of a novel SH3-domain binding protein, Sab,
      which preferentially associates with Bruton's tyrosine kinase (BtK).
AB  - Protein interaction cloning method was used to identify a novel molecule, Sab,
      which binds to the SH3 domain of Bruton's tyrosine kinase (Btk), the deficient
      cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia and murine X
      linked immunodeficiency. Immunoprecipitation using the anti-Sab antibody
      identified the protein product of the gene as a 70 kDa molecule. While Sab does
      not have a proline-rich sequence, it was shown to bind to Btk through the
      commonly conserved structure among SH3 domains. Remarkably, Sab exhibited a high
      preference for binding to Btk rather than to other cytoplasmic tyrosine kinases,
      which suggests a unique role of Sab in the Btk signal transduction pathway.

PMID- 9571152
TI  - A role for the C-terminus of calcitonin in aggregation and gel formation: a
      comparative study of C-terminal fragments of human and salmon calcitonin.
AB  - Calcitonin is used in therapy for osteoporosis and Paget's disease. In vitro,
      human calcitonin forms thick gels which limits its usefulness as a therapeutic,
      and consequently salmon calcitonin which is less prone to aggregate is commonly
      used instead. In order to probe the role of the C-terminal region of the molecule
      in association and gel formation we have prepared a set of three peptides
      corresponding to the C-terminal regions of salmon calcitonin, human calcitonin
      and a mutant of human calcitonin in which Pro-23 is substituted with Ala. The
      peptides are largely disordered in their monomeric state as judged by CD and
      FTIR. All three peptides aggregate and form gels. Both human peptides form a gel
      much faster than the salmon peptide and the proline to alanine mutant forms a gel
      faster than the wildtype human peptide. Gel formation by all three peptides is
      slower than for intact human calcitonin. CD indicates a difference in
      conformation for the human fragment but not for the salmon fragment between the
      monomeric state and the gel state. FTIR experiments suggest the presence of beta
      structure in the gel derived from the human peptide but not in the gel derived
      from the salmon peptide. These results show that there are clear differences in
      the association properties of the peptides and point to a potential role for the
      C-terminal region of calcitonin in controlling aggregation/gel formation.

PMID- 9571153
TI  - Differential assembly kinetics of alpha-tubulin isoforms in the presence of
      paclitaxel.
AB  - The antitumor drug paclitaxel (PTX) inhibits cell growth by binding to
      microtubules, the eukaryotic structures consisting of alpha- and beta-tubulin.
      PTX also promotes the assembly to tubulin in the absence of microtubule
      associated proteins. Although recent studies have implicated beta-tubulin as the
      site of PTX binding, no information is available that relates alpha-tubulin to
      the binding site. In an effort to understand whether the alpha-tubulin is
      involved in the drug binding, we have studied the assembly of alpha-tubulin
      isoforms in the presence of PTX. The assembly results in the presence of 10
      microM paclitaxel (PTX) show that the isoforms assemble at differential rates.
      The rate of assembly for tyrosinated M alpha 1/2 is about three-fold higher than
      that of the nontyrosinated M alpha 1/2 isoform. Such a strikingly different
      assembly behavior of the alpha-tubulin isoforms indicates that alpha-tubulin may
      be involved in the interaction of PTX with microtubules.

PMID- 9571154
TI  - A new step to the mechanism of the enhancement effect of gold nanoparticles on
      glucose oxidase.
AB  - Quantum size effect was strongly supported by the experiment on correlation
      between size of gold nanoparticles (below 10 nm) and activity of glucose oxidase
      attached to them. The attractive enhancement effect of gold nanoparticles on the
      activity of glucose oxidase was then satisfactorily explained. In this
      experiment, 2 nm and 6 nm (average diameter) particles were obtained on monolayer
      matrix. The 2 nm particles proved to be much more able to increase the activity
      of glucose oxidase.

PMID- 9571155
TI  - RAE28, BMI1, and M33 are members of heterogeneous multimeric mammalian Polycomb
      group complexes.
AB  - The Polycomb group loci in Drosophila encode chromatin proteins required for
      repression of homeotic loci in embryonic development. We show that mouse Polycomb
      group homologues, RAE28, BMI1 and M33, have overlapping but not identical
      expression patterns during embryogenesis and in adult tissues. These three
      proteins coimmunoprecipitate from embryonic nuclear extracts. Gel filtration
      analysis of embryonic extracts indicates that RAE28, BMI1 and M33 exist in large
      multimeric complexes. M33 and RAE28 coimmunoprecipitate and copurify as members
      of large complexes from F9 cells, which express BMI1 at very low levels,
      suggesting that different Polycomb group complexes can form in different cells.
      RAE28, BMI1 and M33 interact homotypically, and both RAE28 and M33 interact with
      BMI1, but not with each other. The domains required for interaction were
      localized. Together, these studies indicate that murine Polycomb group proteins
      are developmentally regulated and function as members of multiple, heterogeneous
      complexes.

PMID- 9571156
TI  - E31-K352, the minimal cation binding moiety of Na+,K(+)-ATPase.
AB  - Upon limited tryptic fragmentation of Na+,K(+)-ATPase a 35 kDa fragment (E31
      K352) was formed that bound 204Tl+ on blot. Further fragmentation led to loss of
      binding, pointing to the conclusion that E31-K352 is the minimal cation binding
      unit in Na+,K(+)-ATPase.

PMID- 9571157
TI  - Identification of conserved potentially regulatory sequences of the SRY gene from
      10 different species of mammals.
AB  - We have sequenced the 5' region of the SRY gene from human, chimpanzee, sheep,
      and mouse and from four additional mammalian species, not previously
      characterized (gorilla, gazelle, rat, and guinea pig). In order to identify
      conserved DNA elements potentially involved in the regulation of the SRY gene,
      the newly determined sequences were analyzed and compared to all mammalian SRY
      promoter sequences available at present. Ten highly conserved potential
      regulatory elements have been identified in all 10 species (AP1, Barbie, GATA,
      Gfi1, cMyb, vMyb, NF1, Oct1, Sp1, and SRY). The known function of several of
      these regulatory elements fits well with the known expression of the SRY gene.
      However, except for the highly conserved coding HMG motif, only a short region
      close to the initiation of transcription in the human SRY is conserved in the
      exact position along the gene in all the species analyzed. This lack of sequence
      identity at the orthologous positions is consistent with the suggested rapid
      evolution of the SRY gene. This relative lack of homology contrasts with a high
      sequence identity of the putative regulatory sequences found within each
      taxonomic group of species (primates, bovids, and rodents), which supports a
      common mechanism of SRY expression and possibly also a similar function.

PMID- 9571158
TI  - Defect of an early event of glucose metabolism in skeletal muscle of the male
      Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a non-insulin-dependent diabetes
      mellitus (NIDDM) model.
AB  - Otsuka Long-Evans Tokushima Fatty (OLETF) rats showed that the distribution of
      plasma membrane content of insulin-regulated glucose transporter in skeletal
      muscle was reminiscent of that in human non-insulin-dependent diabetes mellitus
      (NIDDM). To obtain more information on the cellular mechanisms of muscle insulin
      resistance, hexokinase activities were measured in the skeletal muscle of OLETF
      rats. The results showed that the activity of the type II enzyme in the diabetic
      rats was significantly decreased (P < 0.05) compared with Long-Evans Tokushima
      Otsuka (LETO) control rats. No significant differences in the activity of the
      type I hexokinase were observed between these rats. Western blot analysis showed
      that the protein content of the type II in OLETF rats was also significantly
      lower than that in LETO rats (P < 0.05). After insulin stimulation, the
      intramuscular content of glucose 6-phosphate, which regulates glycogen synthesis
      in skeletal muscle, was significantly decreased in OLETF rats (P < 0.01).
      However, glycogen synthase activity in vitro and intramuscular lactate
      concentration in these rats did not show significant differences. These results
      suggest that the G6P content of the diabetic rats is decreased as a result of an
      impaired early event of glucose metabolism, indicating that the molecular defects
      of skeletal muscle in OLETF rats are similar to those in NIDDM patients.

PMID- 9571159
TI  - Characterization of monomeric and homodimeric forms of osteoclastogenesis
      inhibitory factor.
AB  - Osteoclastogenesis inhibitory factor (OCIF) is present naturally as two molecular
      forms, a monomer and a homodimer. The two forms of recombinant human OCIF (rOCIF)
      produced by Chinese hamster ovary (CHO) cells were purified to homogeneity.
      Determination of the C-terminal amino-acid sequences of the two forms of rOCIF
      revealed that the monomeric rOCIF lacked several amino acids including Cys379,
      which is involved in the intermolecular disulfide bond, in its C-terminal region.
      The two forms of rOCIF were indistinguishable in stability, sialic acid content,
      and specific activity in inhibition of osteoclastogenesis. In contrast, the
      homodimeric rOCIF was stronger in heparin-binding ability than the monomeric
      rOCIF. The homodimeric rOCIF was significantly shorter in initial half-life and
      smaller in AUC value in rats than the monomeric rOCIF, but exerted more potent
      biological activity in reducing the calcium concentration in serum of rats than
      did the monomeric rOCIF.

PMID- 9571160
TI  - Rearrangement of the p53 gene in human breast tumours.
AB  - Rearrangement of the p53 gene is frequent in virus transformed cell lines and in
      chronic myelogenous leukemia. It is a rare event in solid tumours and has been
      reported only in osteosarcomas. In this study we have examined rearrangement of
      the p53 gene in human breast tumours. We found rearrangement in 35% of the
      patients (7 of 20 tumours examined). Normal tissue from these patients had an
      unrearranged gene, indicating that the genetic abnormality in the tumour is
      acquired during the natural process of tumorigenesis. No intronic rearrangement
      or allelic loss of the p53 gene was found in the breast tumour samples studied.
      Further, rearrangement of the p53 gene has been correlated with the p53
      transcriptional status. Only two patients with rearranged p53 showed a high level
      of p53 RNA as well as protein expression. Thus, for the first time we report the
      rearrangement of the p53 gene in breast tumours, which may play a role in the
      process of tumorigenesis.

PMID- 9571161
TI  - Morphine modulates NF kappa B activation in macrophages.
AB  - Chronic use of morphine affects the immune system and predisposes an individual
      to opportunistic infections. Macrophages play an important role in conferring a
      first line of defense against invading pathogens. Understanding the mechanisms by
      which morphine affects the functioning of macrophages would have significant
      therapeutic benefit in treatment against infections such as HIV and AIDS related
      syndromes. Two of the major cytokines secreted by activated macrophages are
      Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). Our studies
      show that morphine differentially modulates lipopolysaccharide (LPS) induced
      expression of IL-6 and TNF-alpha. Nanomolar concentrations of morphine synergize
      with LPS and augment the secretion of both IL-6 and TNF-alpha. However, at
      micromolar concentrations morphine inhibits LPS induced synthesis of IL-6 and TNF
      alpha. Expression of both these cytokine genes is dependent on the activation of
      a transcription factor, NF kappa B. Interestingly, morphine treatment also
      modulated the activation of NF kappa B by LPS. Pretreatment with a low dose of
      morphine (nanomolar) resulted in an increase in NF kappa B activation. In
      contrast pretreatment with a high dose of morphine (micromolar) led to a
      significant decrease in NF kappa B activation. Furthermore unlike the
      augmentation which was naloxone reversible, the inhibition of NF kappa B by
      morphine was not reversed by naloxone, suggesting the involvement of a
      nonclassical opioid receptor.

PMID- 9571162
TI  - Differentially expressed snoRNAs in Bungarus multicinctus (Taiwan banded krait).
AB  - Twenty novel snoRNAs forming extensive sequence complementarities to mature 5S
      rRNA were identified from Bungarus multicinctus by reverse transcription
      polymerase chain reaction. It was found that the snoRNA species were
      differentially transcribed in different tissues as evidenced by single stranded
      conformational polymorphism analysis and direct nucleotide sequence analysis.
      Although the diversity in the sequences of snoRNAs is observed, comparison of
      these snoRNA genes reveals that the regions involved in binding to 5S rRNA are
      highly conserved and form two 12-nt-15-nt tracts of complementarity to
      phylogenetically invariant sequences in eukaryotic 5S rRNAs. Nevertheless, the
      lower conservation of box C/D or box H/ACA in these snoRNAs was observed.
      Likewise, the sequences in several fish and human genes forming perfect duplexes
      with 5S rRNA also did not highly retain these box elements. These results may
      infer that the box elements are dispensable for the function of snoRNA species
      identified in the present study. Moreover, the novel finding of the
      differentially expressed snoRNA variants in B. multicinctus suggests that the
      snoRNA genes are selectively processed in different tissues and are likely
      associated with tissue-specific regulation of their host gene transcripts.

PMID- 9571163
TI  - Methylation of nonintegrated multiple copy DNA in plants.
AB  - DNA sequences present in multiple copies in plant genomes are often methylated.
      However, it was not known if methylation occurs on multiple copy DNA molecules
      that are not integrated into the plant genome. To investigate this possibility,
      the methylation state of cauliflower mosaic virus [CaMV] DNA was studied in
      inoculated turnip leaves at different days post-inoculation [DPI]. Unencapsidated
      CaMV DNA was found in an unmethylated state up to 7 DPI. By 9 DPI, viral DNA was
      methylated at almost all HpaII/MspI sites within the CaMV genome. DNA methylation
      did not appear to be preferential but occurred at almost all HpaII/MspI sites at
      approximately the same time. Methylation appeared to occur in an all or none
      manner, suggestive of a switch mechanism. These data strongly suggest that copy
      number-dependent methylation occurs on DNA molecules that are not integrated into
      the genome of a host cell.

PMID- 9571164
TI  - Domain- and site-specific phosphorylation of bovine NF-L by Rho-associated
      kinase.
AB  - Rho-associated kinase (Rho-kinase), the putative target of the small GTP-binding
      protein Rho, phosphorylated neurofilament protein (NF-L) in vitro with
      approximately 1 mole phosphate per mole NF-L. Phosphorylated NF-L no longer
      formed the 10 nm filaments, and NF-L filaments were phosphorylated with a result
      of nearly complete disassembly. NF-L phosphorylated by Rho-kinase was digested
      with trypsin, and digested fragments were assigned by MALDI/TOF. Unique
      phosphorylation sites were found at Ser-26 and Ser-57 in the head domain of NF-L.
      These results indicate that domain- and site-specific phosphorylation by Rho
      kinase may regulate the assembly-disassembly of NF-L filaments.

PMID- 9571165
TI  - Rat maf-related factors: the specificities of DNA binding and heterodimer
      formation.
AB  - maf is a family of genes encoding bZIP transcription factors. We isolated two
      cellular maf-related cDNAs, maf-1 (mafB) and maf-2 (c-maf), from rat and
      determined the specificities of DNA binding and heterodimer formation. Although
      both Mafs strongly bind to MARE, the consensus Maf recognition sequence (MARE, 
      TGCTGACTCAGCA-), originally identified by v-Maf protein Maf-1, recognizes a
      number of sequences containing only the first half of the MARE, -GCTGAC-. On the
      other hand, no such consensus short sequence could be determined for Maf-2. We
      determined the specificities of heterodimer formation with all members of the Jun
      and Fos family. In contrast to v-Maf which forms heterodimers with all Jun and
      Fos proteins, Maf-1 heterodimerizes with all four Fos proteins, but not at all
      with the three Jun proteins. Maf-2 heterodimerizes with c-Fos. We have also found
      that heterodimer formation of Maf-2 with c-Fos dramatically changes the
      specificity of DNA binding and trans-activation activity from that of the Maf-2
      homodimer. These results show that Maf-1 and Maf-2 have significantly different
      properties and they might have different target genes and functions, in spite of
      the similarity of their bZip domain structure.

PMID- 9571166
TI  - Calcium-sensing receptor in mature osteoclasts, which are bone resorbing cells.
AB  - Bone metabolism consists of osteoblast-mediated bone formation coupled to
      osteoclastic resorption of bone. Osteoclastic bone resorption plays an important
      role in normal skeletal development and the maintenance of its integrity
      throughout life. Although osteoclastic activity is thought to be under the
      control of feedback regulation by extracellular cations, the molecular mechanism
      of detecting extracellular cations within the bone microenvironment remains to be
      clarified. In the present study we showed by reverse transcription-polymerase
      chain reaction and Northern blot analysis that cultured mature osteoclasts
      express the calcium-sensing receptor (CaSR) mRNA. The nucleotide sequence of
      rabbit osteoclast CaSR was approximately 90% identical to that of CaSR cDNA from
      human, bovine, and rat parathyroid glands. Moreover, the activity of osteoclastic
      bone resorption, as determined by pit formation, was regulated by extracellular
      calcium ion as well as its agonists that are known to act through the CaSR. We
      conclude that CaSR, homologous to that identified in parathyroid glands, is
      present in mature osteoclasts and calcium ion released from bone may directly
      regulate osteoclastic bone resorption.

PMID- 9571167
TI  - Effects of cell density and trichostatin A on the expression of HDAC1 and p57Kip2
      in Hep 3B cells.
AB  - The interplay between the acetylation and deacetylation activities within the
      cell has been postulated to be a mechanism by which the cell regulates expression
      from genes at the level of chromatin. We have examined the expression pattern of
      the human histone deacetylase gene HDAC1 and the cyclin dependent kinase
      inhibitor p57Kip2 in the hepatocellular carcinoma cell line Hep 3B. HDAC1
      expression was elevated at low cell densities, but once a critical threshold
      point in cell density was attained, expression was reduced to very low levels.
      Treatment of the cells with trichostatin A (TSA), a potent inhibitor of histone
      deacetylases, was found to affect expression. p57Kip2 was found to be
      downregulated by TSA, whereas HDAC1 was upregulated. These effects were found to
      be cell density dependent. The results suggest that HDAC1 plays a role in its own
      regulation, and that investigations using TSA should be carried out when cells
      grow exponentially.

PMID- 9571168
TI  - Possible regulation of the skeletal muscle ryanodine receptor by a polyubiquitin
      binding subunit of the 26S proteasome.
AB  - Proteolytic digestion of ryanodine receptor (RyR) purified from skeletal muscle
      generated 25 short peptides. The amino acid sequences of two, 'KC5' and 'KC7',
      were absent from the RyR primary structure deduced by cDNA cloning. The sequence
      of KC7 corresponded to the N-terminus of the 12 kDa FK506-binding protein, which
      associates with the RyR and modulates its Ca2+ release channel (CRC) function.
      The sequence of KC5 was not similar to any proteins in the databases searched at
      that time. In the present study, the sequence of KC5 was compared to proteins in
      the current Swissprot database release and corresponds most closely to S5a, a
      proteasome subunit. Since S5a targets the 26S proteasome to polyubiquitinated
      proteins, and inositol 1,4,5-trisphosphate receptors, a related class of CRC, are
      down-regulated by a polyubiquitin-dependent mechanism in hormone stimulated
      cells, the abundance of RyRs may be controlled by association with this
      regulatory subunit.

PMID- 9571169
TI  - Dissection of the roles of adenine ring nitrogen (N-1) and exocyclic amino (N-6)
      moieties in the interaction of 2-5A with RNase L.
AB  - To elucidate further the roles played by the adenine bases in the interaction of
      RNase L (EC 3.1.2.6) with the 2',5'-oligoadenylate 2-5A, p5'A2'(p5'A2')np5' A, a
      series of sequence-specific 1-deazaadenosine (c1A)-substituted analogues were
      synthesized and evaluated for their ability to bind to and activate human RNase L
      in comparison to earlier reported inosine-substituted congeners of 2-5A.
      Substitution of only the 5'-terminal adenosine of p5'A2'p5'A2 p5 A with c1A
      afforded an analogue with strongly diminished RNase L binding and activation
      ability, while replacement of the second or middle adenosine of p5 A2' p5'A2'p5'
      A had only a modest effect. In distinct contrast to p5'A2'p5'A2'p5'I, the c1A
      analogue with the third or 2'-terminal adenosine replacement approached parent
      p5' A2'p5'A2'p5' A in RNase L activation ability. These results permitted a
      further dissection of the role of various nucleotidic functional groups in the
      interaction of 2-5A with RNase L: specifically, that the 5'-terminal adenosine
      purine N-1 moiety is key for binding to RNase L, while the 2'-terminal adenosine
      N-6 exocyclic amino group is critical for RNase L activation.

PMID- 9571170
TI  - Butein, a specific protein tyrosine kinase inhibitor.
AB  - Butein, a plant polyphenol, was shown to be a specific protein tyrosine kinase
      inhibitor. This compound inhibited not only the epidermal growth factor (EGF)
      stimulated auto-phosphotyrosine level of EGF receptor in HepG2 cells but also
      tyrosine-specific protein kinase activities of EGF receptor (IC50 = 65 microM)
      and p60c-src (IC50 = 65 microM) in vitro. The inhibition was competitive to ATP
      and non-competitive to the phosphate acceptor, poly (Glu, Ala, Tyr) 6:3:1 for EGF
      receptor tyrosine kinase. In contrast, butein non-significantly inhibited the
      activities of serine- and threonine-specific protein kinases, such as protein
      kinase C (PKC) and cAMP-dependent protein kinase (PKA).

PMID- 9571171
TI  - A drug-lipid interaction model: atropine induces interdigitated bilayer
      structure.
AB  - X-ray diffraction and fluorescence methods have been carried out to examine the
      effects of a drug, atropine, on the structure of model membranes:
      dipalmitoylphosphatidylglycerol(DPPG) multilamella vesicles(MLVs). A structural
      analysis by small angle x-ray diffraction shows that, with incorporation of
      atropine, the lamella repeating period of DPPG MLV is decreased from 5.89 nm to
      4.52 nm. Using fluorescence probe 1,6-diphenyl-1,3,5-hexatriene(DPH) we find that
      the fluorescence intensity of DPH reduces largely at a narrow scope of atropine
      concentration. The experiments of fluorescence polarization of n-(9-anthroyloxyl)
      stearic acid (nAS) and 16-(9-anthroyloxyl)-palmiticacid (16AP) discover that the
      normal polarization gradient almost disappears in DPPG/atropine system. By
      colligating the above results, we can draw a conclusion that atropine induces the
      transition from non-interdigitated to interdigitated stricture of DPPG vesicles
      in gel phase, which provides a sound model of drug-lipid interaction.

PMID- 9571172
TI  - Effect of vascular endothelial growth factor on nitric oxide production by
      cultured rat mesangial cells.
AB  - Vascular endothelial growth factor (VEGF) stimulates nitric oxide (NO) production
      by endothelial cells in vitro and in vivo. However, the impact of VEGF on
      inducible nitric oxide synthase (iNOS) activity and NO synthesis in cultured
      mesangial cells is not known. Therefore, we measured nitrite accumulation in
      cytokine-stimulated, rat mesangial cells (RMC) in response to graded
      concentrations of VEGF. Addition of VEGF (10-50 ng/ml) did not alter RMC
      viability or NO production in either normal (5.6 mM) or high (33.3 mM) glucose
      conditions. Exposure of RMC to VEGF did not modify the effects of L-arginine (20
      mM) or L-NAME (1 mM) on nitrite accumulation in normal or high glucose media. The
      steady state abundance of iNOS mRNA and the cytosolic content of iNOS protein
      were unaffected by addition of VEGF. Cultured RMC expressed the high-affinity
      tyrosine kinase VEGF receptors, flt and flk/KDR, and the levels were not
      modulated by incubation in normal or high glucose media. We conclude that VEGF
      does not regulate proliferation or NO production in cultured RMC. These findings
      suggest that disturbances in the normal interaction between VEGF and NO are not
      involved in the pathogenesis of abnormal mesangial cell structure or function in
      diabetic nephropathy.

PMID- 9571173
TI  - Calcium modulated signaling site in type 2 rod outer segment membrane guanylate
      cyclase (ROS-GC2).
AB  - The ROS-GC subfamily of membrane guanylate cyclases is at present represented by
      two members: ROS-GC1 and ROS-GC2. A unique functional feature of this subfamily
      is that it is intracellularly modulated in low Ca2+ concentration by calmodulin
      like Ca(2+)-binding proteins termed GCAPs, 1 and 2, and the modulation is
      consistent with its linkage to phototransduction. The present study shows that:
      (1) GCAP2 is a specific modulator of ROS-GC2; (2) through systematic remodeling
      of ROS-GC modules, the study also shows that the modulated domain resides within
      the amino acid segment 736-1020. This domain is distinct form the corresponding
      GCAP1-modulated ROS-GC1 domain. Thus, GCAP1 and GCAP2 act through different ROS
      GCs and through two different cyclase domains.

PMID- 9571174
TI  - Alternative splicing of LTBP-3.
AB  - LTBPs bind the 100-kDa latent TGF-beta complex and thereby regulate TGF-beta
      assembly, tissue localization, and function. However, the 100-kDa complex is not
      always associated with LTBP, and, conversely, evidence suggests that LTBP has a
      distinct role in the extracellular matrix. As yet, there are no data to explain
      how the binding interaction between LTBP and the 100-kDa complex is regulated.
      This report provides the first direct evidence of alternative splicing of an LTBP
      gene. Two alternative splice sites in the mouse LTBP-3 gene have been identified
      based on in vivo and in vitro studies. Alternative splicing at one site in
      particular was found to disrupt a structural motif involved in the binding
      interaction with the 100-kDa latent TGF-beta complex. Therefore, alternative
      splicing may represent a molecular mechanism by which the uncomplexed form of
      LTBP-3 is produced, and, as a corollary, by which the 100-kDa latent TGF-beta 1
      complex is produced.

PMID- 9571175
TI  - Cytochrome c oxidase does not catalyze the anaerobic reduction of NO.
AB  - A possible role of reduced cytochrome c oxidase in the metabolism of nitric oxide
      (NO) has been examined with amperometric and stopped-flow photometric techniques.
      Reduced purified cytochrome c oxidase and mitochondria showed no catalytic
      reaction with NO under anaerobic conditions within more than 30 minutes. Only
      fast binding of NO to the reduced enzyme in a 1:1 stoichiometric ratio was
      observed. The NO binding rate was strongly decreased in the presence of 1 mM
      cyanide. These data indicate that, contrary to previous proposals, cytochrome c
      oxidase in the absence of oxygen does not contribute to physiological NO
      metabolism.

PMID- 9571176
TI  - Protein kinase C activation stimulates calcium transport in adrenal zona
      glomerulosa cells.
AB  - Adrenal zona glomerulosa (ZG) cells produce aldosterone in response to
      angiotensin II and extracellular potassium through different mechanisms which
      involve changes in cytosolic free calcium (Cai). Protein kinase C (PKC)
      activation is part of the angiotensin II signalling cascade but its effects on
      Cai are unknown. PKC activation with 1 microM phorbol 12-myristate 13-acetate
      (PMA) and 8 mM Ko significantly increased the rate of calcium influx (P < 0.001).
      Both the PKC- and the Ko-induced calcium influx occurred via a nifedipine
      sensitive pathway. When both were combined, PKC activation and 8 mM Ko were not
      additive over either agent alone. PKC activation and 8 mM Ko also stimulated
      calcium efflux (P < 0.01). When combined together PKC activation and 8 mM Ko had
      additive effects on calcium efflux (P < 0.05). PKC activation did not increase
      Cai nor the exchangeable calcium pool in contrast to 8 mM Ko which significantly
      increased both (P < 0.001). Thus, PKC activation in ZG cells induces a pattern of
      calcium transport characterized by accelerated calcium recycling across the cell
      membrane without increasing cell calcium content.

PMID- 9571177
TI  - Demonstration of adhesion activity of the soluble Ig-domain protein C-CAM4 by
      attachment to the plasma membrane.
AB  - The carcinoembryonic antigen (CEA) family is a large group of proteins with
      immunoglobulin (Ig)-like structures. The membrane-associated CEA-family proteins
      have been shown to mediate intercellular adhesion. In addition to these membrane
      associated proteins, several secreted CEA-like proteins, such as C-CAM4, PSG1b,
      and PSG11s, have also been identified. The functions of these soluble proteins
      are not clear because they cannot support intercellular adhesion like the
      membrane-associated proteins can. A fundamental question important for
      understanding the functions of these soluble proteins is whether they can
      interact in a homophilic fashion as do many of their membrane-associated
      homologues. We found that the homophilic interactions between these soluble
      proteins were too weak to be detected by solution binding assays. This is not
      unexpected because interactions between adhesion molecules are usually transient
      and weak to allow for control of association and dissociation. By expressing
      these soluble CEA-family proteins, C-CAM4, PSG1b, and PSG11s, as membrane
      anchored forms, we showed that C-CAM4 could mediate intercellular adhesion,
      whereas PSG1b and PSG11s, despite their 52% identity to C-CAM4, could not. These
      results suggest that C-CAM4, but not PSG1b and PSG11s, can probably form
      homodimers. Thus, these secretory CEA-family members most likely have different
      interaction mechanisms, i.e., C-CAM4 might function as dimers, while PSGs might
      function as monomers.

PMID- 9571179
TI  - Mapping of novel genes predisposing or protecting diabetes development in the
      BB/OK rat.
AB  - By several crossing studies it has been demonstrated that the MHC class-II genes
      of the RT1u haplotype, Iddm1, and the lymphopenia, Iddm2, are essential, but not
      sufficient for diabetes development in the BB rat. Using diabetic BB/OK and
      diabetes-resistant DA rats it has been shown that a third non-MHC gene, Iddm3, on
      chromosome 18 cosegregates with diabetes in the BB/OK rat subline. Because
      mapping results need not be consistent among different crosses, we genetically
      analysed a new cross population using diabetic BB/OK and diabetes-resistant
      SHR/Mol rats analysing 73 microsatellite markers. The genetic analysis of Iddm1
      and Iddm2 homozygous [(BB/OK x SHR)F1 x BB/OK] first backcross hybrids (BC1)
      confirmed the action of Iddm3 and one predisposing non-MHC locus, Iddm4, near
      Ighe/D6Mgh2 on chromosome 6 and one protective locus, Iddm5r(esistance), detected
      around Igf2/Tnt on chromosome 1. From these novel findings it is concluded that
      the diabetogenic phenotype of the BB/OK rat subline is the result of the
      interaction of predisposing and protecting diabetes genes.

PMID- 9571178
TI  - Expression of a hepatitis C virus NS3 protease-NS4A fusion protein in Escherichia
      coli.
AB  - Both the NS3 protease and the NS4A protein are required for efficient cleavage of
      the nonstructural protein region of the hepatitis C virus polyprotein. The NS3
      protease domain was fused at its C-terminal end with full length NS4A and
      expressed in Escherichia coli. This protein (NS3 delta-NS4A) was purified to
      apparent homogeneity after refolding from extracts recovered from inclusion
      bodies. During the expression and purification process, NS3 delta-NS4A was not
      auto-processed in either a cis or trans manner at NS3/NS4A junction site. When
      the kcat/K(m) values and thermostability of NS3 delta-NS4A were compared with
      those for maltose binding protein-NS3 fusion protein (MBP-NS3), which contains
      only NS3 region, the single-chain NS3 delta-NS4A showed enhanced proteolytic
      activities and thermostability.

PMID- 9571180
TI  - Oxidation of individual fatty acids yields different profiles of oxidation
      markers.
AB  - Free radicals attack lipid molecules and initiate a chain of reactions that may
      trigger several diseases such as atherosclerosis and cancer. Several markers of
      oxidative stress have been proposed, including measurements of lipid peroxides
      and short-chain aldehydes levels and evaluation of conjugated diene formation.
      Although it is generally assumed that fatty acid oxidizability is directly
      proportional to their degree of unsaturation, little is known about the
      contribution of individual fatty acids to each of these markers. We investigated
      such contributions in a model of AAPH-mediated peroxidation of individual fatty
      acid micelles by assessing several indices of oxidative stress. The results
      suggest that the generation of oxidation products by individual fatty acids is
      not directly related to their degree of unsaturation and indicate that the
      differential contribution of individual fatty acids should be taken into account
      and more than one marker of lipid peroxidation should be included in in vivo
      studies of oxidative stress.

PMID- 9571181
TI  - Human pigmentation phenotype: a point mutation generates nonfunctional MSH
      receptor.
AB  - alpha-Melanocyte stimulating hormone (alpha-MSH) regulates skin and hair
      pigmentation by modulating the activity of MSH receptor (MC1R). We have
      identified Arg151Cys variant of human MC1R in genomic DNA isolated from a person
      with red hair and light skin of type I. The Arg151Cys variant of MC1R binds to
      radio-labelled analogue of alpha-MSH with identical affinity as wild type MC1R
      but can not be stimulated to produce cyclic AMP (cAMP). The mutation Arg151Cys
      renders human MC1R completely nonfunctional, which explains the red hair, light
      skin and poor tanning ability (skin type I). This is the first report ever
      describing a nonfunctional MC1R isolated from a human subject.

PMID- 9571182
TI  - Effects of brief glucocorticoid exposure on growth of vascular smooth muscle
      cells in culture.
AB  - While prolonged exposure of vascular smooth muscle cells (VSMC) to glucocorticoid
      has been shown to inhibit cell proliferation, the effect of a brief pulse
      exposure is not known. We studied the short-term effects of pulse exposure to
      dexamethasone (DEX) on DNA synthesis in cultured VSMC. VSMC were pulsed with DEx
      for varying time intervals and [3H]thymidine incorporation into cells after 24 h
      was measured. Exposure to DEX for 24 h decreased [3H]thymidine incorporation,
      while pulse treatments with DEX from 2 min to 6 h significantly increased
      [3H]thymidine incorporation. Maximal proliferative effect was observed with a 20
      min exposure. The effect of a 20-min pulse was dose-dependent, with the half
      maximal dose of DEX being approximately 10(-7) M. A selective glucocorticoid
      receptor antagonist, RU486, inhibited the proliferative effect of DEx.
      Concentrated conditioned medium from cells exposed to 10(-6) M DEX increased
      [3H]thymidine incorporation by other VSMC in a dose-dependent manner. These
      results suggest that short-term pulse DEX exposure is capable of producing one or
      more autocrine growth factors in VSMC via a glucocorticoid receptor action. This
      effect of glucocorticoid pulses may contribute to the pathogenesis of
      arteriosclerosis and hypertension.

PMID- 9571183
TI  - Oxidation decreases low density lipoprotein association with the subendothelium
      extracellular matrix.
AB  - Atherosclerosis is initiated by accumulation of low density lipoprotein (LDL) in
      the subendothelium extracellular matrix (ECM) followed by oxidation and scavenger
      receptor mediated uptake by the vessel wall recruited macrophages. The effect of
      oxidation on LDL association with the ECM is not yet clear. In the present study
      we examined the hypothesis that excessive oxidation of LDL results in decreased
      LDL association with ECM, thereby increasing its accessibility to the scavenger
      receptor on macrophages. We have studied the relative association of Cu+2 ion
      oxidized LDL to native LDL with the native or oxidized bovine corneal endothelial
      cells ECM. Oxidation of LDL decreased its binding to the ECM. The kinetic of this
      process was characterized by approximately 1 h lag phase followed by a
      significant decreased binding of 80% after 6.5 h oxidation. This kinetic more
      closely resembled the pattern of the oxidation product dienals accumulation
      rather than thiobarbituric acid reactive substance formation. Oxidation of ECM
      bound LDL resulted in an increased LDL release from the ECM as a function of Cu+2
      ion concentration with a maximal increase of 2-fold at 3 microM. ECM oxidation
      prior to exposure to LDL resulted in a 30% decrease in LDL binding to the ECM. In
      conclusion, these results suggest that oxidation processes in the vessel wall
      result in increased dissociation of ECM-bound LDL, which in turn makes this
      oxidized LDL more accessible for binding and uptake by macrophages leading to
      foam cell formation.

PMID- 9571184
TI  - Acute and chronic effects of leptin on glucose utilization in lean mice.
AB  - Experiments described here show that in vivo glucose uptake is impaired in mice
      given 30 micrograms leptin by intraperitoneal injection 2 hours before an oral
      glucose tolerance test (GTT). When mice were infused for 7 days with 10
      micrograms/day leptin, the 4-fold increase in circulating leptin caused a
      transient hypophagia, a sustained weight loss and significantly inhibited insulin
      release in response to an oral GTT. Adipocytes from these mice were not insulin
      responsive whereas insulin-stimulated muscle and liver glycogen synthesis were
      increased. In contrast, leptin added to 2 hour in vitro incubations had an
      insulin-like effect on muscle glucose utilization and augmented insulin
      stimulation of adipocyte lipid synthesis. Thus, normal mice treated chronically
      with leptin develop tissue specific changes in insulin sensitivity and compensate
      for inhibition of glucose-stimulated insulin release. The contrasting response to
      acute leptin exposure suggests these changes are not a direct effect of the
      protein.

PMID- 9571185
TI  - Regulation of hormone-sensitive lipase expression by glucose in 3T3-F442A
      adipocytes.
AB  - Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in adipocyte
      lipolysis. We have studied the effect of glucose and long chain fatty acids on
      the HSL mRNA content of 3T3-F442A adipocytes. Exposure of the cells for 32 h to a
      medium without glucose led to a decrease by a factor of 2.5-3 in the HSL mRNA
      without a change in C/EBP alpha mRNA or triglyceride content of the adipocytes.
      The reduction in HSL mRNA level was accompanied by a decrease in HSL total
      activity. The effect of glucose exposure was observed after 24 h of exposure and
      was reversible. Treatment of the adipocytes with oleate did not affect HSL
      expression. These data show that glucose modulates HSL gene expression and hence
      could participate in the regulation of adipose tissue lipolysis.

PMID- 9571186
TI  - Regulation of the p53 protein by protein kinase C alpha and protein kinase C
      zeta.
AB  - The C-terminal of p53 (amino-acids 368-383) represses the DNA binding activity of
      p53. In vitro, phosphorylation of this region by Protein Kinase C (PKC) is
      associated with increased DNA binding activity. However, whether PKC can directly
      modulate p53 function in vivo is not known. Here, we demonstrate that
      cotransfection of p53 with either PKC alpha or PKC zeta increases p53's
      transcriptional activity. Mutagenesis of p53 indicates that serine 371 is the
      major site for phosphorylation by PKC alpha in vitro. Mutation of serine 371
      caused a small decline in p53 activation by PKC alpha and PKC zeta. However, the
      alternatively spliced murine p53, which lacks the PKC phosphorylation sites,
      still demonstrated increased transcriptional activation when cotransfected with
      either PKC alpha or PKC zeta. The results indicate that phosphorylation of p53 by
      PKC in vitro does not correlate with the ability of PKC to upregulate p53's
      transcriptional activity in vivo.

PMID- 9571187
TI  - A novel insertion mutation (A169i) in the CLN1 gene is associated with infantile
      neuronal ceroid lipofuscinosis in an Italian patient.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a progressive encephalopathy
      characterized by psychomotor deterioration, early visual loss, and an evanishing
      EEG. Mutations in the CLN1 gene encoding palmitoyl-protein thioesterase (ppt)
      have been reported in all Finnish INCL patients and in several non-Finnish North
      European patients. No cases have been contributed from the Mediterranean area
      thus far. We identified a single adenine insertion at nucleotide position 169
      (A169i) in the CLN1 gene in a family in which the proband suffered from an INCL
      like syndrome. The novel mutation was homozygous in blood from the proband,
      heterozygous in his healthy parents, and not found in control alleles. The
      mutation leads to an early stop codon resulting in an abnormal and truncated ppt
      protein. Our observations provide the first molecular characterization of an
      Italian INCL patient and expand the list of the known defects in INCL.

PMID- 9571188
TI  - Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with
      diabetes.
AB  - Mutation in the mitochondrial gene at position 3243 was recently identified in a
      large pedigree of diabetes mellitus and deafness. As the mitochondria play an
      important role in glucose-stimulated insulin secretion in pancreatic beta-cells,
      we therefore searched for such mutations to detect a candidate gene for diabetes.
      We screened 10 diabetic subjects with clinical features suggesting mitochondrial
      DNA mutations. An adenine to guanine point mutation in tRNA(Lys) in at position
      8296 (the 8296 mutation) was newly identified. Subsequently, we screened 1216
      diabetic subjects, 44 patients with sensorineural deafness subjects and 300 non
      diabetic control subjects for this mutation. We identified the mutation in 11
      (0.90%) unrelated diabetic subjects, one (2.3%) patient with deafness and no non
      diabetic control subject. Seven of these 12 subjects showed maternal inheritance.
      Deafness was seen in 7 of 12 probands. Four family pedigrees showed maternal
      inheritance of diabetes over two or three generations. Subjects carrying the 8296
      mutation may develop diabetes and the mutation can explain as high as ca. 1% of
      the causes of diabetes.

PMID- 9571189
TI  - Dissipation of mitochondrial membrane potential by exogenous phospholipid
      monohydroperoxide and protection against this effect by transfection of cells
      with phospholipid hydroperoxide glutathione peroxidase gene.
AB  - Two hours after its addition to cultures of a guinea pig cell line, 104C1,
      dilinoleoyl phosphatidylcholine monohydroperoxide (PCOOH) at concentrations of 5
      160 microM induced a dissipation of the mitochondrial inner membrane potential
      (delta psi m), without any apparent morphological changes, in the cells. The
      PCOOH-induced loss of delta psi m was restored 4 hr after the replacement of the
      medium with PCOOH-free fresh medium. In contrast, 104C1/O4C cells, a stable clone
      from 104C1 cells transfected with the human phospholipid hydroperoxide
      glutathione peroxidase (PHGPx) gene encoding a sequence including a signal
      peptide towards mitochondria, were resistant to the loss of delta psi m after a 2
      hr exposure to PCOOH at concentrations up to 160 microM. Even after an 8-hr
      exposure to 80 microM PCOOH, the transfected cells retained their delta psi m
      intact, though the parent cells were killed by the same treatment. The present
      results strongly suggest that the expression of PHGPx protected the host cells
      from PCOOH-mediated injury at least by protecting their mitochondria from lipid
      hydroperoxide-induced loss of delta psi m.

PMID- 9571190
TI  - Diurnal change of the cold-inducible RNA-binding protein (Cirp) expression in
      mouse brain.
AB  - RNA-binding proteins are believed to play important roles in regulation of neural
      functions. Recently, a mouse cDNA encoding the cold-inducible RNA-binding
      protein, Cirp, has been isolated, the amino acid sequence of which showed
      similarity to plant circadian rhythm proteins. In the present study, diurnal
      expression of Cirp in the mouse nervous system was examined. Northern blot
      analysis showed that the level of Cirp mRNA was diurnally regulated in the brain
      but not in the testis and liver. The level increased during the daytime and
      decreased during the nighttime. Immunohistochemistry using an anti-Cirp antibody
      showed that Cirp was expressed in the nucleus of neurons and that the level of
      Cirp was diurnally regulated in the suprachiasmatic nucleus and the cerebral
      cortex. The diurnal regulation was not observed in the brain of adult mice kept
      in constant darkness nor that of 3-day-old mice. These findings suggest that Cirp
      plays a role in biological rhythms as known for plant proteins and that
      expression of Cirp is regulated differentially in discrete brain regions.

PMID- 9571191
TI  - Identification of cell surface binding sites for PC-cell-derived growth factor,
      PCDGF, (epithelin/granulin precursor) on epithelial cells and fibroblasts.
AB  - PC cell derived growth factor (PCDGF) is an 88-kDa glycoprotein purified from the
      culture medium of the highly tumorigenic mouse teratoma-derived cell line PC.
      PCDGF was shown to stimulate the proliferation of 3T3 fibroblasts and PC cells.
      Amino acid sequencing of PCDGF indicated its identity to the precursor for the 6
      kDa polypeptides epithelins and granulins. In this paper, we investigated the
      binding of PCDGF to the mink lung epithelial cell line CCL64. Scatchard analysis
      indicates that 125I-PCDGF binding to CCL64 cells is curvilinear, corresponding to
      the existence of two classes of binding sites: high affinity binding sites (560
      +/- 170 sites/cell) with a Kd1 of 43 +/- 15 pM and low affinity binding sites
      (16,350 +/- 5900 sites/cell) with a Kd2 of 3.9 +/- 1.9 nM. 125I-PCDGF was
      chemically crosslinked to cell surface receptors on CCL64 cells with
      disuccinimidyl suberate. A major crosslinked band of about 190 kDa with
      radiolabeled PCDGF was detected after SDS-PAGE, suggesting the presence of PCDGF
      binding sites with molecular weight of about 120 kDa. 125I. PCDGF crosslinking
      studies indicate the presence of PCDGF binding sites with a molecular weight
      similar to those of binding sites on CCL64 cells on the surface of two other
      PCDGF-responsive cell lines, 3T3 fibroblasts and PC cells. These data suggest
      that the receptors for PCDGF are widely distributed on cells of distinct
      embryonic origin.

PMID- 9571192
TI  - Cloning, molecular characterization, and distribution of a gene homologous to
      delta opioid receptor from zebrafish (Danio rerio).
AB  - A full-length cDNA, ZFOR1, has been isolated from the teleost zebrafish (Danio
      rerio) using a probe from rat mu opioid receptor. ZFOR1 encodes a 373 amino acid
      protein with seven potential transmembrane domains that shows a high degree of
      homology to mammalian delta opioid receptor. We have also isolated a genomic
      clone which contains two exons of ZFOR1, homologous to exons 2 and 3 in mouse and
      human delta opioid receptor. Expression of ZFOR1 appears to be restricted to
      nervous tissue as assessed by Northern blot. In situ hybridization in zebrafish
      brain with specific probes revealed several discrete areas of ZFOR1 expression;
      higher levels are detected in dorsal telencephalic areas, the periventricular
      layer of the optic tectum, and the granular layer of the cerebellum. This is the
      first molecular evidence of the presence of the delta opioid receptor in a non
      mammalian species and suggests that it has been highly conserved throughout
      vertebrate evolution.

PMID- 9571193
TI  - Lactoferrin markedly inhibits hepatitis C virus infection in cultured human
      hepatocytes.
AB  - We found that bovine lactoferrin (bLF), a milk protein belonging to the iron
      transporter family, effectively prevented hepatitis C virus (HCV) infection in
      cultured human hepatocytes (PH5CH8), a cell line susceptible to HCV infection and
      supportive of HCV replication. Because preincubation of HCV with bLF was required
      to prevent the infection of HCV to the cells, and preincubation of bLF with the
      cells showed no inhibitory effect on HCV infection, we demonstrated that the anti
      HCV activity of bLF was due to the interaction of bLF with HCV, but not due to
      the interaction of bLF with the cells. We further found that human lactoferrin
      also had anti-HCV activity, but bovine transferrin, the other member of the iron
      transporter family, did not have anti-HCV activity. Our findings suggest that
      lactoferrin is one of candidates for an anti-HCV reagent that will be well
      tolerated and effective in the treatment of patients with chronic hepatitis.

PMID- 9571194
TI  - Transforming G protein-coupled receptors block insulin and ras-induced adipocytic
      differentiation in 3T3-L1 cells: evidence for a PKC and MAP kinase independent
      pathway.
AB  - We have used the expression of muscarinic m1 receptors in the preadipocytic 3T3
      L1 cell line for dissecting the nature of the G protein-linked pathways governing
      adipocytic differentiation, a complex process controlled by many stimuli and
      their downstream targets. 3T3-L1 cells can be differentiated by insulin or by ras
      oncogenes, and MAP kinase has been implicated in this process. However, m1
      stimulation failed to induce differentiation of 3T3-L1 cells. Furthermore, it
      prevented insulin or v-ras-induced adipocytic differentiation, utilizing a
      protein kinase C-independent pathway. m1 stimulation did not alter the
      phosphorylation state of the insulin receptor substrates IRS-1 and SHC, nor the
      recruitment of Grb-2. Interestingly, whereas m1 receptors potently activated MAP
      kinase, another differentiation-inhibitor, TNF alpha, did not affect it. These
      results suggest that the control of adipocytic differentiation can occur
      utilizing a biochemical route independent of protein kinase C, and acting
      downstream, or independently from the Ras-MAP kinase pathway.

PMID- 9571195
TI  - Sam68 is a Ras-GAP-associated protein in mitosis.
AB  - Sam68 is the major tyrosine-phosphorylated and Src-associated protein in mitotic
      cells. Sam68 stimulates G1/S transition and this effect is dependent on the
      integrity of its KH domain (hnRNPK Homology) which confers nucleic acid binding
      properties. During mitosis, Sam68 undergoes tyrosine phosphorylation, which
      negatively regulates its nucleic acid binding properties and mediates the
      interaction of Sam68 with critical SH2-containing signaling proteins such as
      Grb2, PLC gamma 1 and Ras-GAP. However, the interaction of Ras-GAP with Sam68 has
      been brought into question, based on the lack of co-immunoprecipitation between
      Sam68 and Ras-GAP in interphase cells. Here we show that the choice of anti-Ras
      GAP antibodies is critical for the detection of Ras-GAP/Sam68 complex formation,
      and that this interaction is specific for G2/M transition in both NIH3T3 and Src
      transformed cells. Such data reinforce the importance of the interaction of Ras
      GAP with RNA binding proteins during cell proliferation through its SH2 and SH3
      domains.

PMID- 9571197
TI  - The rfb genes in Azotobacter vinelandii are arranged in a rfbFGC gene cluster: a
      significant deviation to the arrangement of the rfb genes in Enterobacteriaceae.
AB  - We report the identification of rfbF and rfbC located adjacent to the previously
      identified rfbG (Gavini et. al. Biochem. Biophys. Res. Commun. 1997, 240, 153
      161) from the non-symbiotic, non-pathogenic soil bacterium Azotobacter
      vinelandii. The rfbF open reading frame encodes a putative polypeptide of 256
      amino acids. This polypeptide shares a homology of 74% with the RfbF of
      Synechocystis sp. and a 70% homology with the AscA of Yersinia pseudotuberculosis
      which function as alpha-D-glucose-1-phosphate cytidylyltransferases in the
      biosynthesis of the O-antigen. The rfbC encodes a putative polypeptide of 186
      amino acids. It shows strongest homology to the RfbC of Synechocystis sp. (64%)
      and Salmonella typhimurium (40%). RfbC functions as a dTDP-4-Dehydrorhamnose 3,5
      Epimerase. The genes identified here have a low G + C content (approximately 56%)
      as compared to the A. vinelandii chromosome (approximately 63%) which is
      characteristic of the rfb clusters identified in other bacteria and may be
      indicative of the acquisition of the rfb genes by interspecific gene transfer.
      Despite the high level of sequence conservation, the organization of the rfb
      genes in A. vinelandii deviates from the arrangement of the most thoroughly
      studied rfb gene clusters of Enterobacteriaceae.

PMID- 9571196
TI  - Nonsteroidal anti-inflammatory drugs may delay the repair of gastric mucosa by
      suppressing prostaglandin-mediated increase of hepatocyte growth factor
      production.
AB  - Prostaglandins (PGs), hepatocyte growth factor (HGF), and induction of
      cyclooxygenase (PG synthetase, COX) play important roles in the repair process of
      gastric mucosa. We hypothesized that nonsteroidal anti-inflammatory drugs
      (NSAIDs), including indomethacin (IND), retard the healing of ulcers by
      suppressing these factors. In this study, we investigated the effects of
      cytokines, growth factors, and IND on production of PG and HGF, and induction of
      COX using cultured human gastric fibroblasts. Exogenous PGs significantly
      increased HGF production in a dose-dependent manner. Among various potential
      stimulants tested, interleukin-1 beta (IL-1 beta) dramatically increased PGE2
      production and significantly stimulated HGF production. IL-1 beta induced COX-2
      but not COX-1 protein. IND significantly reduced both basal and IL-1 beta-induced
      PGE2 release and HGF production. These results suggest that the IL-1 beta-PG-HGF
      pathway plays a role in the repair process of gastric mucosa. Further, NSAIDs may
      delay the healing of gastric mucosal ulcer, in part through suppression of HGF
      expression via inhibition of endogenous PG production.

PMID- 9571198
TI  - Ribozyme targeting of receptor for advanced glycation end products in mouse
      mesangial cells.
AB  - Accumulation of extracellular matrix is a characteristic of diabetic nephropathy,
      and advanced glycation end products (AGEs) are considered to play an important
      role in the mechanism. To investigate the involvement of the receptor for AGE
      (RAGE) in upregulation of type IV collagen by AGEs, we applied the hammerhead
      ribozyme for targeting RAGE. We established a stable mouse mesangial cell line
      that produces the RAGE-specific ribozyme (Rz-RAGE). Both the RAGE mRNA and
      protein were decreased in the cell line. The amount of type IV collagen mRNA
      increased by AGEs' treatment in control cells. In contrast, the increase of type
      IV collagen induced by AGEs was not observed in the Rz-RAGE-producing cells. We
      conclude that the induction of type IV collagen by AGEs is mediated by RAGE and
      this mechanism could be involved in diabetic nephropathy. This study also
      suggested the experimental/therapeutic potential of hammerhead ribozymes.

PMID- 9571199
TI  - Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis.
AB  - The number of members of the recently defined DEG/ENaC sodium channel superfamily
      is increasing. Their importance in Na transport, taste perception, acid sensing,
      and mechanotransduction has been implicated. We have cloned a new member of this
      superfamily from human testis, which was named hTNaC1 (for human testis sodium
      channel 1). The hTNaC1 has 532 amino acid residues with two hydrophobic
      transmembrane domains. It has the highest identity (82%) with a rat H(+)-gated Na
      channel specific for sensory neurons (DRASIC) and a low identity (29%) with an
      epithelial isoform (alpha-ENaC) of this superfamily. Northern blot of human
      tissues revealed its selective expression in testis (7 kb) and absence in other
      tissues. The identification of a new member of Na channel specifically expressed
      in testis will expand the role of this channel family to the reproduction
      physiology.

PMID- 9571200
TI  - The metallo-disintegrin ADAM10 (MADM) from bovine kidney has type IV collagenase
      activity in vitro.
AB  - The metallo-disintegrins (ADAMs) are a family of mammalian proteins with
      significant amino acid sequence identity and a domain organisation similar to the
      snake venom metalloproteinases (reprolysins). They have been implicated in a wide
      variety of processes such as cell-cell and cell matrix adhesion and proteolysis
      of the extracellular matrix in a wide variety of cell types. They may also be
      involved in events such as the processing of plasma membrane proteins,
      proteolysis in the secretory pathway and pro-cytokine conversion processes. Due
      to the close relationship of the ADAM proteins with snake venom enzymes which
      have been demonstrated to be type IV collagenases, we investigated whether
      purified bovine ADAM10 could cleave basement membrane type IV collagen. We show
      here that ADAM10 purified from bovine kidney can cleave a basement membrane
      collagen type IV preparation as assessed by SDS-PAGE analysis and novel epitope
      recognition with a specific antibody to type IV collagen. The demonstration that
      a metallo-disintegrin displays a type IV collagenase activity may be relevant to
      tumour metastasis and may have general relevance to extracellular re-modeling in
      renal pathology and a variety of other pathological states where compromise of
      the basement membrane is involved.

PMID- 9571202
TI  - Attenuation of LPA-mediated calcium signaling and inositol polyphosphate
      production in rat-1 fibroblasts transformed by the v-src oncogene.
AB  - Alterations in cellular signaling underlie the transforming actions of many
      oncogenes. The vsrc oncogene tyrosine kinase, pp60vsrc, is known to alter
      multiple signal transduction pathways, including those involving
      phosphatidylinositol (PI) metabolism. In this study, we investigated the effects
      of vsrc-transformation on lysophosphatidic acid (LPA) receptor coupling to
      intracellular free calcium [Ca2+]i and PI turnover in rat-1 fibroblasts. In
      normal rat-1 cells, LPA rapidly elevated [Ca2+]i (EC50 = 10nM). In contrast, the
      ability of LPA to mobilize calcium was markedly attenuated in rat-1-vsrc cells.
      Further study revealed that the LPA-mediated generation of inositol (1,4,5)P3 and
      other inositol polyphosphates was also markedly attenuated in the vsrc
      transformed cells. Although LPA caused a transient reduction in the level of
      PI(4,5)P2 in normal rat-1 cells, the agonist elevated the level of PI(4,5)P2 in
      the vsrc-transformed cells. These findings demonstrate that vsrc-transformation
      alters the coupling of LPA receptors to PI turnover and calcium signaling in rat
      1 cells, and point to G protein-coupled receptor systems as targets for
      modulation by the vsrc kinase.

PMID- 9571201
TI  - Cloning of the human mitochondrial 51 kDa subunit (NDUFV1) reveals a 100%
      antisense homology of its 3'UTR with the 5'UTR of the gamma-interferon inducible
      protein (IP-30) precursor: is this a link between mitochondrial myopathy and
      inflammation?
AB  - We report the cloning of the genomic and cDNA of the human 51 kDa subunit
      (NDUFV1) of mitochondrial complex I. The 6 kbp NDUFV1 gene is composed of 10
      exons. All intron-exon boundaries comply to the consensus sequence for splice
      donor and acceptor sites. Within the 5' flanking region we identified a putative
      binding site for NRF-2, a GATA- and GC-box element. Canonical TATA- or CCAAT
      boxes were absent, the transcriptional start site, however, lies within a CpG
      island, which is consistent with the "housekeeping" function of the gene. Within
      the coding sequence we detected consensus motifs for NADH, FMN, and iron-sulfur
      binding sites. The amino acid sequence homology between human and cow is 96.9%.
      Surprisingly we found a 48 bp long complete antisense homology between the 3'UTR
      of the NDUFV1-mRNA and the 5'UTR of the mRNA for the gamma-interferon inducible
      protein precursor (IP-30). This finding is intriguing since both genes lie on
      different chromosomes. The exact function of IP-30 is not yet known, but it may
      play a role in gamma-interferon mediated immune reactions. The NDUFV1-mRNA might
      act as an antisense suppresser, thus restraining translation of IP-30 in tissues
      with high energy demand. This finding could be a molecular link between complex I
      deficiency and inflammatory myopathy which have been repeatedly described to
      occur together.

PMID- 9571203
TI  - Histone H2A.F/Z subfamily: the smallest member and the signature sequence.
AB  - The nucleotide sequence of a 700 basepair cDNA obtained from rabbit bladder was
      determined. It encodes a 123 amino acid protein, which is the smallest member of
      histone H2A.F/Z subfamily. The known H2A.F/Z variants are highly conserved in
      their central core regions of about 100 amino acids but more divergent in their N
      and C-terminal ends. In addition to the seven amino acid signature sequence
      previously known for the H2A proteins, all the cloned H2A.F/Z variants contain an
      identical peptide sequence, L-E-Y-L-T-A-E-V-L-E-L-A-G-N-A. This 15 amino acid
      motif is proposed here as the signature sequence to identify new members of the
      H2A.F/Z subfamily.

PMID- 9571204
TI  - Solubilization of hydrophobic peptides by reversible cysteine PEGylation.
AB  - "PEG-a-Cys" reagent, synthesized by the esterification of monomethoxy
      poly(ethylene glycol) (avg. MW = 5 kDa) to Ellman's reagent [5,5'-dithiobis(2
      nitrobenzoic acid)], is shown to "PEGylate" reversibly the cysteine residue of a
      25-residue synthetic hydrophobic peptide (H2N-REAAALAAAAALAAWAALCPARRRR-CO2H)
      designed to model a transmembrane segment of a membrane protein. A mixed
      disulfide bond was formed between the reagent and the peptide that was readily
      cleaved with the mild reducing agent tricarboxyethylphosphine hydrochloride
      (TCEP.HCl). Carboxypeptidase B digestion of the charged carboxyl terminus of the
      peptide through to the Ala residue--which mimics the enzymatic cleavage of a TM
      segment from a fusion protein--releases a highly hydrophobic peptide. A time
      dependent decrease in the amplitude of the digested peptide circular dichroism
      (CD) spectra was attributed to the aggregation and/or precipitation of the
      peptide. While PEGylation of the peptide with PEG-a-Cys had a negligible effect
      on conformation, it inhibited the loss of CD amplitude in both intact and
      digested peptides, suggesting that it was effective in solubilization of
      hydrophobic peptides.

PMID- 9571205
TI  - Allelic variants of human calcitonin receptor: distribution and association with
      bone mass in postmenopausal Italian women.
AB  - Bone mass could be under control of several polymorphic genes which can modulate
      bone turnover via reciprocal interactions. One of the genes that can be involved
      in this process is the calcitonin receptor (CTR) gene. Evidence from cDNA cloning
      has shown that CTRs have seven potential transmembrane domains and they are known
      to be expressed in several tissues. In a Japanese population was discovered a
      novel Restriction Fragment Length Polymorphism (RFLP) at the CTR gene by Alu I
      restriction enzyme at the 1377th nucleotide expressing either proline (CC
      genotype) or leucine (TT genotype) as the 463rd amino acid. The heterozygote
      genotypes were indicated as TC. In the present study we analyzed the presence of
      this CTR gene RFLP in 307 postmenopausal Italian women. We observed that TC and
      TT genotypes represented the most frequent CTR genotypes in Italian women. In
      addition, Duncan's test used to compare the genotypes showed that TT genotype has
      significant lower lumbar BMD in comparison with CC genotype.

PMID- 9571207
TI  - Regulation of the DBP promoter by PAR proteins and in leukemic cells bearing an
      E2A/HLF translocation.
AB  - The D-site binding protein (DBP) is a member of the PAR domain subfamily of b/ZIP
      proteins, whose expression in the liver is highly sensitive to the growth state
      of that organ. This paper examines the regulation of the DBP promoter by C/EBP
      alpha and examines the role of autoregulation in its expression. Of four
      previously characterized proximal promoter sites, sites I and III are shown to
      bind C/EBP alpha, but cotransfection in Hep G2 cells of a C/EBP alpha expression
      vector is unable to transactivate the promoter. In contrast, the expression of
      DBP, particularly in conjunction with the related protein HLF, is able to
      dramatically upregulate expression directed by the proximal promoter. Deletion
      analysis and the use of single site reporter constructs demonstrate that sites II
      and IV are highly responsive to transactivation by DBP and HLF. The DBP promoter
      is active in the UOC-B1 cell line, which bears a 17:19 translocation resulting in
      the creation of an E2A:HLF fusion protein. The proteins binding to site IV are
      elevated in this line, suggesting that upregulation of DBP expression in response
      to inappropriate HLF activity may be mediated through this site.

PMID- 9571206
TI  - Syntaxin 11: a member of the syntaxin family without a carboxyl terminal
      transmembrane domain.
AB  - We have cloned a novel syntaxin-like molecule, designated human syntaxin 11
      (hsyn11). The open reading frame encodes a polypeptide of 287 amino acids with
      potential coiled-coil domains. hsyn11 has extensive homology to members of the
      syntaxin family, particularly syntaxin 1 and syntaxin 2. Unlike other members of
      the syntaxin family, however, hsyn11 has a short cysteinerich carboxyl-terminal
      tail but not a typical hydrophobic domain which may serve as a membrane anchor.
      Northern blot analysis revealed two transcripts of approximately 0.8 kb and
      approximately 1.7 kb in length that are particularly abundant in heart and
      placenta, although lower levels were also detectable in other tissues except in
      the brain. Consistent with the lack of a distinct membrane anchorage sequence in
      hsyn11, indirect immunofluorescence microscopy of transiently expressed N
      terminally myc-tagged hsyn11 revealed a diffuse, cytoplasmic labeling.

PMID- 9571210
TI  - Enantioselective epoxide hydrolysis: catalysis involving microbes, mammals and
      metals.
AB  - Although alkyl epoxides are difficult to synthesize in enantiomerically pure form
      they can often be prepared by the enantioselective hydrolysis of racemic epoxide.
      The best methods for this transformation are all catalytic and they illustrate
      the complementary role that biological and synthetic catalysts can play in
      organic chemistry.

PMID- 9571212
TI  - Elsewhere in biology

PMID- 9571211
TI  - Deconstructing gelsolin: identifying sites that mimic or alter binding to actin
      and phosphoinositides.
AB  - Gelsolin is involved in cytoskeletal remodeling as it can fragment and guide
      reassembly of actin networks. Recent advances in defining the structure of
      gelsolin identified functionally important sites. These structural insights could
      lead to the design of small molecule analogs to enhance, inhibit or mimic the
      functions of gelsolin.

PMID- 9571213
TI  - Starving cancer into submission. EntreMed, Inc.

PMID- 9571214
TI  - Web alert. Searching for a job.

PMID- 9571215
TI  - Functional homodimeric glycoprotein hormones: implications for hormone action and
      evolution 
AB  - Background:. Human chorionic gonadotropin (hCG), lutropin, follitropin, and
      thyrotropin act as alphabeta heterodimers to control reproduction and thyroid
      function. The alpha and beta subunits of these proteins are divided into three
      loops (alpha1, alpha2,alpha3; beta1,beta2,beta3) by cysteine knots and the
      heterodimer is stabilized by 20 beta-subunit residues wrapped around alpha2 like
      a seatbelt. Understanding how these hormones interact with their receptors, a
      matter of considerable dispute, would facilitate design of pro- and anti
      fertility agents. Results:. By swapping alpha2 for beta2 and vice versa and, in
      some cases, adding an amino-terminal coiled-coil dimerization domain, we prepared
      homodimeric analogs that have the conformation found in each 'half' of hCG.
      Homodimers containing loops beta1,alpha2,beta3 and none, part, or all of the
      seatbelt stimulated signal transduction to the same extent as hCG, albeit with
      lower potency. Those containing alpha1,beta2,alpha3 were inactive. Conclusions:.
      The activities of homodimers containing the beta1,alpha2,beta3 groove exceed
      those of other minimized analogs more than 100-1000-fold, suggesting this portion
      of the hormone forms the major receptor contact. The discovery that glycoprotein
      hormone heterodimers can be converted to functional homodimers supports the
      proposal that this protein family evolved from an active homodimeric ancestor by
      gene duplication and acquisition of mutations to loop 2 that prevent
      homodimerization. This approach to protein minimization should be applicable to
      other proteins composed of architecturally related subunits, including those that
      might have arisen by gene duplication.

PMID- 9571217
TI  - DNA damage induced via independent generation of the radical resulting from
      formal hydrogen atom abstraction from the C1'-position of a nucleotide 
AB  - Background:. Deoxyribonucleotide radicals resulting from formal C1'-hydrogen atom
      abstraction are important reactive intermediates in a variety of DNA-damage
      processes. The reactivity of these radicals can be affected by the agents that
      generate them and the environment in which they are produced. As an initial step
      in determining the factors that control the reactivity of these important radical
      species, we developed a mild method for their generation at a defined site within
      a biopolymer. Results:. Irradiation of oligonucleotides containing a photolabile
      nucleotide produced C1'-DNA radicals. In the absence of potential reactants other
      than O2, approximately 90% of the damage events involve formation of alkaline
      labile lesions, with the remainder resulting in direct strand breaks. The ratio
      of alkaline-labile lesions to direct strand breaks ( approximately 9:1) is
      independent of whether the radical is generated in single-stranded DNA or double
      stranded DNA. Strand damage is almost completely quenched under anaerobic
      conditions in the presence of low thiol concentrations. Competition studies with
      O2 indicate that the trapping rate of C1'-DNA radicals by beta-mercaptoethanol is
      approximately 1.1 x 10(7) M-1 s-1. Conclusions:. The mild generation of the C1'
      DNA radical in the absence of exogenous oxidants makes it possible to examine
      their intrinsic reactivity. In the absence of other reactants, the formation of
      direct strand breaks from C1'-radicals is, at most, a minor pathway. Competition
      studies between beta-mercaptoethanol and O2 indicate that significantly higher
      thiol concentrations than those in vivo or some means of increasing the effective
      thiol concentration near DNA are needed for these reagents to prevent the
      formation of DNA lesions arising from the C1'-radical under aerobic conditions.

PMID- 9571218
TI  - Intestinal absorption and stability of morphine 6-glucuronide in different
      physiological compartments of the rat.
AB  - Morphine 6-glucuronide (M6G) is an active metabolite of morphine that could be
      used as a drug, but its hydrolysis into morphine remains controversial. We
      investigated the acidic hydrolysis of M6G and found that the recovery of morphine
      did not exceed 5%. The stability of M6G was studied in different physiological
      compartments of male Sprague-Dawley rats. The formation of morphine after M6G
      incubation in feces was under 2% in the small intestine, whereas the formation of
      morphine in colon feces represented 85.6 +/- 12.9% of the initial concentration
      of M6G. The stability of M6G was also determined ex vivo using the isolated
      perfused rat liver. The hepatic extraction ratio of M6G was very low (0.04 +/-
      0.02), but 88. 7 +/- 11.2% of the dose was excreted in bile. The elimination half
      life of M6G in the perfusate (66.4 +/- 20.6 min) was higher than the elimination
      half-life in bile (18.6 +/- 2.5 min). The hydrolysis of M6G was low, with only
      7.7% and 0.03% of morphine in the perfusate and bile, respectively. The perfusate
      level of morphine 3-glucuronide (M3G) resulting from morphine conjugation was 4.9
      +/- 3.6%. An in vivo experiment demonstrated that after oral administration, M6G
      was absorbed per se in the proximal intestine, and the process was prolonged over
      the 24-hr experiment due to its reabsorption following enterohepatic
      recirculation. Finally, 10.5 +/- 4.3% of morphine and 12.9 +/- 5.1% of M3G
      compared with M6G AUCs were found in plasma. These results show that M6G is
      weakly converted into morphine when orally absorbed, with a kinetic profile
      similar to a slow release formulation.

PMID- 9571219
TI  - Metabolism of MK-499, a class III antiarrhythmic agent, in rats and dogs.
AB  - MK-499 [(+)-N-[1'-(6-cyano-1, 2, 3, 4-tetrahydro-2(R)-naphthalenyl)-3, 4-dihydro
      4(R)-hydroxyspiro(2H-1-benzopyran-2, 4'-piperidin)-6-yl]methanesulfonamide]
      monohydrochloride is an investigational class III antiarrhythmic agent for
      treatment of malignant ventricular tachyarrhythmias. The disposition of [3H]MK
      499 and [14C]MK-499 was studied in rats and dogs after oral and iv
      administration. MK-499 was concentrated in organs of excretion and the heart. In
      the rat, urinary radioactivity elimination values after iv (0.5 mg/kg) and oral
      (6.25 mg/kg) doses were 21 +/- 3% and 10 +/- 2%, respectively. Corresponding
      fecal recoveries were 68 +/- 6% and 78 +/- 7%. Similar results were found after
      corresponding doses of [14C]MK-499. In dogs, urine and feces accounted for 16 +/-
      3% and 75 +/- 4% of recovered radioactivity after a [3H]MK-499 iv dose (0.1
      mg/kg). Corresponding recoveries after an oral dose (1 mg/kg) were 12 +/- 2% and
      76 +/- 3%. Biliary (0-24 hr) excretion accounted for 39 +/- 5% and 41 +/- 18% of
      [3H] and [14C] oral doses in rats, respectively. Dogs excreted 34% of [3H] oral
      dose in (0-24 hr) bile. The data indicated that a substantial amount of MK-499
      was absorbed by rats and dogs. MK-499, metabolite I (formed by loss of N
      substitution), and metabolite II (an acid formed by metabolic scission across the
      benzopyran ring) each represented 30% of rat urinary label. Rat bile contained MK
      499 (10%), II (20%), and IV (10%), which was formed by carbon-4 hydroxylation of
      the tetralin ring. Additionally, rat bile included glutathione (V) and N-acetyl-1
      cysteine (VI) conjugates of a ring-opened metabolite. Metabolite III, a
      positional isomer of IV, was excreted in rat urine. The major labeled species
      excreted in dog bile were unchanged MK-499 and its glucuronide (VII), which,
      respectively, represented 50% and 30% of the biliary radioactivity. MK-499 and a
      small amount of I represented dog urinary radioactivity. The bioavailability of
      MK-499 was high in dogs (100%) but low in rats (17%). This difference was
      probably due to the more extensive presystemic metabolism of MK-499 in rats.

PMID- 9571220
TI  - Site-selective differences in cytochrome P450 isoform activities. Comparison of
      expression in rat and rhesus monkey lung and induction in rats.
AB  - The distribution of pulmonary cytochrome P450 (P450 or CYP) isoforms has been
      investigated primarily in immunohistochemical studies, which are neither
      quantitative nor reflective of the functions of these enzymes. Studies of enzyme
      activities have been performed using whole-lung homogenates or isolated cells,
      but there is little information on the regioselective expression of P450
      monooxygenases. The aims of this study were to compare the activities of P450
      monooxygenases in different lung subcompartments in two commonly studied animal
      models, i.e. rats and monkeys, and to explore the possibility that inducing
      agents would result in activity up-regulation that is highly site-selective,
      using rats as a model. Microdissection techniques were used to separate the
      airways from blood vessels and lung parenchyma. In rats, CYP1A1 (ethoxyresorufin)
      and CYP2B (pentoxyresorufin) dealkylase activities were highest in the
      parenchyma, whereas CYP2E1 (p-nitrophenol) hydroxylase activity was highest in
      the airways. P450 reductase activities were similar in airways and parenchyma and
      were lower in trachea. In monkeys, no significant site-selective differences in
      CYP1A1 and CYP2B1 activities were found. In contrast, CYP2E1 activity was higher
      in the distal bronchioles and parenchyma than in the proximal airways. P450
      reductase activities were similar in microsomes prepared from all subcompartments
      of monkey lung. Induction of rat CYP1A1 activity by beta-naphthoflavone
      (administered ip) was much greater in the airways and lung parenchyma (
      approximately 30-fold) than in the liver ( approximately 10-fold) or trachea (
      approximately 2.5-fold). Oral administration of phenobarbital or acetone
      increased CYP2B and CYP2E1 activities in rat liver but had no significant effect
      on P450 activities in subcompartments of rat lung. These findings support the
      conclusion that there are regiospecific and species-specific differences in the
      activities of P450 isoforms and that the inducibility of rat pulmonary P450s is
      dependent on the isoform and lung region.

PMID- 9571221
TI  - Mechanism of ascorbic acid enhancement of the bioavailability and diuretic effect
      of furosemide.
AB  - The following possible explanations for the significant increases in the oral
      bioavailability and the diuretic and natriuretic effects of orally administered
      furosemide observed when ascorbic acid was coadministered to dogs were
      investigated: ascorbic acid might enhance the gastrointestinal (GI) absorption of
      furosemide, might inhibit GI wall metabolism of furosemide, might enhance the
      reabsorption of furosemide from the renal tubules, and might increase the
      unionized fraction of furosemide at the receptor sites. The significant increase
      in the oral bioavailability with coadministration of ascorbic acid seemed to
      result from reduced gastric first-pass metabolism of furosemide and not enhanced
      GI absorption of furosemide. This might be supported by rat studies; the
      percentages of the oral doses of furosemide recovered from the GI tract at 8 hr
      after oral administration were similar (p < 0.583) without (39.5%) and with
      (44.7%) coadministration of ascorbic acid, and the amounts of furosemide
      remaining per gram of stomach after 30-min incubations of 50 micrograms of
      furosemide with 9000g supernatant fractions of stomach homogenates were increased
      significantly (48.5 vs. 42.4 micrograms) by the addition of 100 micrograms of
      ascorbic acid. The significant increases in the diuretic and natriuretic effects
      of furosemide with ascorbic acid could be the result of increases in the
      reabsorption of furosemide from renal tubules and increases in the unionized
      fraction of furosemide at the renal tubular receptor sites. This was supported by
      1.5-4.2-fold increases in urine output and approximately 20% decreases in the
      time-averaged renal clearance of furosemide when the urine pH was decreased by
      1.5-2.5 units by oral administration of ammonium chloride.

PMID- 9571222
TI  - Biotransformation of irbesartan in man.
AB  - The metabolism of irbesartan, a highly selective and potent nonpeptide
      angiotensin II receptor antagonist, has been investigated in humans. An aliquot
      of pooled urine from healthy subjects given a 50-mg oral dose of [14C]irbesartan
      was added as a tracer to urine from healthy subjects that received multiple, 900
      mg nonradiolabeled doses of irbesartan. Urinary metabolites were isolated, and
      structures were elucidated by mass spectroscopy, proton NMR, and high-performance
      liquid chromatography (HPLC) retention times. Irbesartan and the following eight
      metabolites were identified in human urine: (1) a tetrazole N2-beta-glucuronide
      conjugate of irbesartan, (2) a monohydroxylated metabolite resulting from omega-1
      oxidation of the butyl side chain, (3, 4) two different monohydroxylated
      metabolites resulting from oxidation of the spirocyclopentane ring, (5) a diol
      resulting from omega-1 oxidation of the butyl side chain and oxidation of the
      spirocyclopentane ring, (6) a keto metabolite resulting from further oxidation of
      the omega-1 monohydroxy metabolite, (7) a keto-alcohol resulting from further
      oxidation of the omega-1 hydroxyl of the diol, and (8) a carboxylic acid
      metabolite resulting from oxidation of the terminal methyl group of the butyl
      side chain. Biotransformation profiles of pooled urine, feces, and plasma samples
      from healthy male volunteers given doses of [14C]irbesartan were determined by
      HPLC. The predominant drug-related component in plasma was irbesartan (76-88% of
      the plasma radioactivity). None of the metabolites exceeded 9% of the plasma
      radioactivity. Radioactivity in urine accounted for about 20% of the radiolabeled
      dose. In urine, irbesartan and its glucuronide each accounted for about 5 to 10%
      of the urinary radioactivity. The predominant metabolite in urine was the omega-1
      hydroxylated metabolite, which constituted about 25% of the urinary
      radioactivity. In feces, irbesartan was the predominant drug-related component
      (about 30% of the radioactivity), and the primary metabolites were
      monohydroxylated metabolites and the carboxylic acid metabolite. Irbesartan and
      these identified metabolites constituted 90% of the recovered urinary and fecal
      radioactivity from human subjects given oral doses of [14C]irbesartan.

PMID- 9571223
TI  - Urinary excretion of cyclophosphamide in humans, determined by phosphorus-31
      nuclear magnetic resonance spectroscopy.
AB  - Phosphorus-31 NMR spectroscopy was used to analyze urine samples from patients
      treated with cyclophosphamide (CP) on 2 consecutive days. CP and all of its known
      phosphorylated metabolites except the tautomeric pair 4
      hydroxycyclophosphamide/aldophosphamide, i.e. carboxycyclophosphamide (CXCP),
      dechloroethylcyclophosphamide (DCCP), alcophosphamide, ketophosphamide, and
      phosphoramide mustard (PM), were determined. Several other signals corresponding
      to unknown CP-related compounds were observed. Seven of them were identified; all
      were hydrolysis products of CP or its metabolites (one from CP, two from CXCP,
      three from DCCP, and one from PM). Twenty-four-hour urinary excretion of
      unmetabolized CP was not significantly different on the first (17% of the daily
      administered dose) and second (16%) days of treatment. The amounts of
      phosphorylated metabolites excreted in 24-hr urine samples were much higher after
      the second CP dose (37%) than after the first (20%), suggesting autoinduction of
      CP metabolism. CXCP and its two degradation products (accounting for 7-10% of
      CXCP) were by far the major metabolites (11.5 and 23% after the first and second
      doses, respectively). DCCP plus its degradation products and alcophosphamide each
      represented 2-3% on the first day of treatment and 5% on the second day of
      treatment. Levels of PM and its degradation products were extremely low (0.3 and
      0.6% after the first and second CP doses, respectively), as were those of
      ketophosphamide (0.4 and 0.6% on the first and second days of treatment,
      respectively). We noted only modest interpatient variation in excreted levels of
      CP and all of its metabolites.

PMID- 9571224
TI  - Metabolic and dispositional fate of 1,2-dibromo-2,4-dicyanobutane in the male
      fischer 344 Rat.
AB  - Studies were conducted to characterize the absorption, disposition, metabolism,
      and excretion of 1,2-dibromo-2,4-dicyanobutane (BCB; methyldibromoglutaronitrile)
      following iv, oral, and topical administration to male Fischer 344 rats.
      Following iv administration of [14C]BCB (8 mg/kg, 120 microCi/kg), no parent
      compound was detected in the blood; however, its debrominated metabolite, 2
      methyleneglutaronitrile (2-MGN; Cmax 7.3 micrograms/ml), was observed up to 1 hr.
      Within 72 hr, greater than 60% of the dose was excreted in the urine and 4.1% in
      the feces, and 6.6% was exhaled as 14CO2. Although less than 5% of the dose was
      retained in tissues, approximately 12% was bound to the erythrocyte fraction of
      the blood. Following oral administration of [14C]BCB (80 mg/kg, 100
      microgramsCi/kg), approximately 85% of the dose was absorbed, whereas 72% of the
      dosed radioactivity was recovered in the urine and 9.7% in the feces, 7.5% was
      exhaled as 14CO2, 3.5% bound to tissues, and 2. 6% bound to blood. Although
      parent compound could not be detected in the blood following oral administration,
      2-MGN was detected (Cmax 0. 32 micrograms/ml). Following topical application of
      [14C]BCB (25 mg/kg, 50 microgramsCi/kg), less than 12% of the dose was absorbed,
      with the major route of excretion being the urine (6.6% of dose). Urinary
      metabolite profiles were nearly identical for each route of administration, and
      the primary urinary metabolite was a mercapturate conjugate of 2-MGN that was
      identified as N-acetyl-S-(2, 4-dicyanobutane)-L-cysteine. BCB was found to be
      extremely labile in whole blood, plasma, and glutathione containing solutions,
      and in each case the formation of 2-MGN could be reduced by the alkylation of
      free-sulfhydryls with N-ethylmaleimide. These results suggest that BCB is totally
      debrominated prior to systemic distribution, and tissue exposure to intact BCB
      seems to be exceedingly low regardless of route of administration.

PMID- 9571225
TI  - Disposition of 1,2-[14C]Dibromoethane in male Wistar rats.
AB  - In this study the disposition of 1,2-[14C]dibromoethane (1, 2-[14C]DBE) was
      investigated in male Wistar rats. 1,2-DBE is a cytotoxic and carcinogenic
      compound that has been used as an additive in leaded gasoline and as a fumigant.
      1,2-[14C]DBE was administered orally or iv. Radioactivity was recovered (mostly
      within 48 hr after administration) in urine (75-82% of the dose), feces (3.2-4%
      of the dose), and expired air (0.53-7.2% of the dose). One hundred-sixty-eight
      hours after administration of 1,2-[14C]DBE, most of the radioactivity in tissues
      was found in the liver, lungs, and kidneys (<1% of the dose) and the red blood
      cells (0.3% of the dose). Identified urinary metabolites were S-(2
      hydroxyethyl)mercapturic acid, thiodiacetic acid, and thiodiacetic acid
      sulfoxide, together accounting for, on average, 78% of the total amount of
      radioactivity in urine. In addition to S-(2-hydroxyethyl)mercapturic acid,
      thiodiacetic acid, and thiodiacetic acid sulfoxide, several compounds were
      anticipated as potential urinary metabolites of 1,2-DBE, i.e. S
      (carboxymethyl)mercapturic acid, S-(2-hydroxyethyl)thioacetic acid, S-(2
      hydroxyethyl)thiopyruvic acid, S-(carboxymethyl)thiopyruvic acid, S-(2
      hydroxyethyl)thiolactic acid, and S-(carboxymethyl)thiolactic acid. All of the
      postulated urinary metabolites were synthesized and searched for in urine
      samples. None of these metabolites could be detected in urine, however. The data
      obtained in the present study might be useful for risk assessment and
      biomonitoring studies of 1,2-DBE and will also be used to further validate a
      physiologically based pharmacokinetic model for 1, 2-DBE in rats and humans that
      was recently developed.

PMID- 9571226
TI  - Metabolism and excretion of a new anxiolytic drug candidate, CP-93, 393, in
      healthy male volunteers.
AB  - CP-93,393 [(7S,9aS)-1-(2-pyrimidin-2-yloctahydropyrido[1,2-a] pyrazin-7
      ylmethyl)pyrrolidine-2,5-dione] is a new anxiolytic drug with highly selective
      serotonin 5-hydroxytryptamine 1A autoreceptor agonist, alpha2-adrenergic
      antagonist, and dopamine D2 agonist properties. The excretion, biotransformation,
      and pharmacokinetics of CP-93,393 were investigated in six healthy male
      volunteers after oral administration of a 5-mg dose of [14C]CP-93,393. The
      administered radioactivity was excreted predominantly in the urine. One week
      after administration of the dose, cumulative excretion amounted to 67.8 +/- 2.5%
      in the urine and 22.0 +/- 5.6% in the feces. In total, 89.8 +/- 5.7% of the
      radioactive dose was recovered in urine and feces. Mean maximum plasma
      concentration values for unchanged CP-93,393 were 10.92 and 1.02 ng/ml for poor
      metabolizers (PMs) and extensive metabolizers (EMs) of dextromethorphan,
      respectively. AUC0-infinity values for unchanged CP-93,393 were also greater for
      PMs than for EMs, whereas the mean maximum plasma concentration and AUC0-infinity
      values for total radioactivity were similar for the two phenotypes. Less than
      0.5% of the dose was excreted in urine as unchanged drug for both EMs and PMs,
      suggesting extensive metabolism of CP-93,393 in both phenotypes. Hydroxylation at
      the 5-position of the pyrimidine ring was identified as the main metabolic
      pathway. 5-Hydroxy-CP-93,393 (M-15) and its glucuronide and sulfate conjugates (M
      7 and M-13, respectively) accounted for approximately 51% of the administered
      dose in excreta of both PMs and EMs. Hydrolysis of the succinimide ring, in
      combination with 5-hydroxylation and/or conjugation or not, accounted for
      approximately 9% of the dose. A novel metabolite, apparently resulting from
      oxidative degradation of the pyrimidine ring, was characterized as the amidine
      analog M-18. M-15 (47-62%), its sulfate conjugate (M-13, approximately 9%), and
      the pyrimidine ring-cleaved product (M-18, 7-13%) were identified as the major
      circulating metabolites for both EMs and PMs. Therefore, CP-93,393 undergoes
      metabolism by three primary pathways, i.e. 1) aromatic hydroxylation followed by
      conjugation with glucuronic acid and sulfuric acid, 2) oxidative degradation of
      the pyrimidine ring, and 3) hydrolysis of the succinimide ring. The identified
      metabolites accounted for approximately 90, 91, and 92% of the total
      radioactivity present in urine, plasma, and feces, respectively. The major in
      vivo oxidative metabolites were also observed after in vitro incubations with
      human liver microsomes.

PMID- 9571227
TI  - Studies on the stereoselective internal acyl migration of ketoprofen glucuronides
      using 13C labeling and nuclear magnetic resonance spectroscopy.
AB  - Internal acyl migration reactions of drug 1beta-O-acyl glucuronides are of
      interest because of their possible role in covalent binding to serum proteins and
      consequent allergic reactions as well as their influence on drug disposition. An
      approach using 13C labeling and nuclear magnetic resonance (NMR) spectroscopy has
      been used to investigate in situ the kinetics of acyl migration and hydrolysis of
      1beta-O-acyl glucuronides of enantiomeric ketoprofens (KPs) in phosphate buffer
      solutions at 37 degrees C. Apparent first-order degradation of the 1beta-O-acyl
      glucuronide labeled in the ester carbonyl carbon and the sequential appearance of
      2-, 3-, and 4-O-acyl isomers as both alpha- and beta-anomeric forms were observed
      for each enantiomer. All of the positional isomers and anomers were characterized
      using two-dimensional NMR spectroscopy (heteronuclear multiple bond correlation,
      correlated spectroscopy, totally correlated spectroscopy) of the reaction
      mixtures. The overall degradation rate constants (hr-1) of (R)- and (S)-KP
      glucuronides were 1.07 +/- 0.154 and 0.55 +/- 0.034, respectively. To evaluate in
      detail the stereoselective reactivity, a kinetic model describing the
      rearrangement reactions was constructed, and the kinetics were simulated using a
      theoretical approach. Only the acyl migration, 1beta-->2beta, was found to have
      significant stereoselectivity. The rate constants (hr-1) for 1beta-->2beta
      migration of (R)- and (S)-KP glucuronides were 1.04 +/- 0.158 and 0. 52 +/-
      0.029, respectively. The results may suggest that (R)-KP glucuronide could be
      more susceptible to covalent binding to proteins via acyl migration than the
      corresponding antipode. This stereoselective reactivity may be responsible for
      the stereoselective pharmacokinetics of KP. The direct approach using 13C
      labeling and NMR spectroscopy could also provide insight into the reactivities of
      other labile drug acyl glucuronides and their isomeric glucuronides.

PMID- 9571228
TI  - Hepatic clearance models: comparison of the dispersion and Goresky models in
      outflow profiles from multiple indicator dilution rat liver studies.
AB  - The multiple indicator dilution (MID) technique is often used for investigation
      of the kinetic behavior of substrates and metabolites in eliminating organs. The
      present study was a systematic comparison of the utility of the Goresky model
      (GM) (a structural model) and the mixed-boundary dispersion model (DM) (a
      stochastic model) in the interpretation of influx, efflux, and removal
      (sequestration) coefficients, with data generated from rat liver-perfusion/MID
      studies. Although the GM and the DM are equivalent in their descriptions of
      membrane transport, they differ in their classifications of the dispersion of
      blood-borne elements. For the DM, the dispersion is an inverse Gaussian
      distribution of vascular transit times; for the GM, it is accounted for by the
      dispersion observed among noneliminated reference indicators (e.g. labeled red
      blood cells, albumin, sucrose, and H2O) or the derived reference. In this study,
      previously published rat liver-perfusion/MID data obtained for the glutathione
      conjugate of bromosulfophthalein and hippuric acid, compounds that exhibit
      saturable carrier-mediated transport, with the GM were reanalyzed with the two
      compartment DM. When the fitted values for volume and transfer coefficients were
      compared, good correlation was found between the fitted vascular volume for the
      DM and the vascular volume for the reference indicator for the GM. The influx
      coefficients were generally similar between the models, but improved
      correspondence was observed when the DM was modified to include the large-vessel
      transit time. In contrast, the efflux and sequestration coefficients obtained for
      the DM did not correspond well to those from the GM. The disagreement was due, in
      part, to differences in the interpretation of the late-in-time component of the
      reference transit time distribution curve, which was not described well by the
      DM. Consequently, the residence time distribution and the relative dispersion
      were underestimated by the DM.

PMID- 9571229
TI  - Effects of phenobarbital on stereoselective metabolism of ifosfamide in rats.
AB  - Plasma and urinary levels of ifosfamide (IF) enantiomers and their metabolites 2
      dechloroethylifosfamide, 3-dechloroethylifosfamide, 4-hydroxyifosfamide, and
      isophosphoramide mustard were determined for control and phenobarbital-treated
      male Sprague-Dawley rats by using pseudoracemates and GC/MS and stable-isotope
      dilution analytical methods. For the control rats, the mean AUC for (S)-IF in
      plasma was greater than that for (R)-IF (R/S AUC ratio, 0.78) and the mean half
      life of 41.8 min for (S)-IF was slightly longer than that of 34.3 min for (R)-IF.
      Phenobarbital pretreatment significantly decreased the AUC values for (R)-IF and
      (S)-IF, to 21 and 30% of the control values, respectively, and shortened plasma
      half-lives for both enantiomers [half-life for (R)-IF, 19.8 min; half-life for
      (S)-IF, 19.4 min]. The urinary excretion values for (R)-IF and (S)-IF were
      decreased to 41 and 30% of the control values, respectively. The overall amounts
      of the metabolites in urine were concomitantly increased. Additionally, there
      were significant reversals in both the R/S AUC ratio and the urinary excretion of
      3-dechloroethylifosfamide. Moreover, the enantioselectivity for the generation of
      4-hydroxyifosfamide and isophosphoramide mustard disappeared after phenobarbital
      treatment. These results strongly suggested that the 4-hydroxylation and
      dechloroethylation of IF enantiomers were mediated by different P450 isozymes or
      the same isozyme with different stereochemical selectivities.

PMID- 9571230
TI  - Chlorzoxazone 6-hydroxylase and p-nitrophenol hydroxylase as the most suitable
      activities for assaying cytochrome P450 2E1 in cynomolgus monkey liver.
AB  - Western blot analyses of liver microsomes from 13 male and 12 female monkeys
      demonstrated that in each sample a variable amount of a cytochrome P450 (P450)
      protein, likely monkey P450 2E1, cross-reacted with anti-rat P450 2E1 antibodies.
      Therefore, the involvement of monkey 2E1 in the oxidation of typical substrates
      for 2E1 from other species, such as dimethylnitrosamine (DMN), p-nitrophenol
      (pNP), chlorzoxazone (CLZ), and aniline, was investigated. Kinetic studies using
      microsomes from five male and five female monkeys showed that CLZ and pNP
      hydroxylations were monophasic, with apparent KM values of 77 and 14 microgramsM,
      respectively, whereas aniline hydroxylation and DMN demethylation were
      multiphasic, suggesting that P450s other than 2E1 were involved in catalyzing the
      latter two reactions. When correlation analyses were performed using several
      monooxygenase activities determined in male and female monkey liver specimens, it
      was found that immunodetectable 2E1 contents were highly correlated (r >/= 0.75)
      with CLZ and pNP hydroxylations, weakly correlated (r = 0.6) with aniline
      hydroxylation, and not correlated with DMN demethylation or other monooxygenase
      activities; CLZ hydroxylation was strongly correlated with pNP hydroxylation,
      weakly correlated with aniline hydroxylation, and not correlated with DMN
      demethylation. Inhibition experiments showed that CLZ and pNP hydroxylations were
      immunoinhibited by 60-80% by anti-rat P450 2E1 and were inhibited by the
      prototypical 2E1 inhibitor 4-methylpyrazole with IC50 values of 1.5 and 13
      microgramsM, respectively. In conclusion, the findings provide evidence that P450
      2E1 is constitutively and equally expressed in male and female monkey liver and
      it exerts a major role only in hydroxylation of CLZ and pNP.

PMID- 9571231
TI  - Refinement of an in vitro cell model for cytochrome P450 induction.
AB  - Induction of cytochromes P450 (P450s) by drugs can lead to drug-drug
      interactions. Primary hepatocytes have been reported to retain inducible P450s.
      To optimize the use of primary hepatocytes for predicting induction of P450 (CYP
      3A and 2B) expression in vivo, both culture conditions and expression of
      induction potentials were investigated. In rat hepatocytes, basal CYP 3A1/2
      expression was better maintained in cells cultured on Matrigel compared with
      collagen when low concentrations of dexamethasone were used. However, CYP 3A1/2
      induction was not affected by either matrix. In contrast, induction of CYP 2B1/2
      by phenobarbital was markedly stronger in hepatocytes cultured on Matrigel. To
      further validate the in vitro model, Sprague-Dawley rats and isolated hepatocytes
      cultured on Matrigel were exposed to a series of compounds. In an attempt to
      minimize large variability between experiments, a novel approach for calculating
      induction potential was applied. In vitro results for CYP 3A1/2 and 2B1/2
      induction correlated well with those observed in vivo. In contrast with rat
      hepatocytes, basal CYP 3A4 expression in human hepatocytes decreased rapidly in
      cells cultured on either Matrigel or collagen. However, CYP 3A4 inducibility was
      retained in cells cultured on either matrix. Interestingly, induction of CYP 3A4
      in human hepatocytes by several model compounds did not correlate with the
      induction of CYP 3A1/2 in rat hepatocytes. This in vitro assay should facilitate
      the demand for a fast and reproducible method for addressing P450 induction by
      numerous compounds at the drug discovery stage.

PMID- 9571232
TI  - Metabolism-based inactivation of penile nitric oxide synthase activity by
      guanabenz.
AB  - Guanabenz (Wytensin) was shown to inactivate nitric oxide synthase (NOS) activity
      in vitro and in vivo. In in vitro studies with the use of a cytosolic fraction
      from penile tissue, the inactivation was found to depend on NADPH, time, and the
      concentration of guanabenz. The L-, but not the D-, isomer of arginine could
      protect from the inactivation, suggesting an active site-directed event. The
      kinetics of inactivation could be described by an apparent dissociation constant
      for the initial reversible complex (Ki) and a pseudo first-order inactivation
      constant (kinact) of 38.5 microM and 0.179 min-1, respectively. In in vivo
      studies, guanabenz was shown to inhibit penile cytosolic NOS activity in a dose-
      and time-dependent manner. Treatment of rats with guanabenz (5 mg/kg/day) for 4
      days caused a decrease of approximately one-half in the NOS activity of the
      penile cytosolic fraction with a concomitant loss in the amount of
      immunodetectable NOS protein. Treatment for 4 days at a dose of 0. 5 mg/kg/day
      showed a similar decrease in activity, whereas a dose of 0.05 mg/kg/day showed no
      effects. Due to the multitude of processes that are regulated by NO, the
      inactivation of NOS is a potential mechanism to be considered in a variety of
      biological effects associated with drugs.

PMID- 9571233
TI  - Substrate selectivity of mouse N-acetyltransferases 1, 2, and 3 expressed in COS
      1 cells.
AB  - Two human acetyl-CoA:arylamine N-acetyltransferases (NAT1 and NAT2) have been
      identified. Therapeutic and carcinogenic agents that are substrates for these
      isoenzymes (including isoniazid, sulfamethazine, p-aminobenzoic acid, 5
      aminosalicyclic acid, and 2-aminofluorene) have been used to evaluate the role of
      the N-acetylation polymorphisms of NAT1 and NAT2 in the treatment of disease and
      differential risk of various cancers among individuals of differing acetylator
      phenotypes. The mouse is frequently used as a model of the human acetylator
      polymorphism. As three Nat isoenzymes have been identified in mouse, it is
      necessary to determine the selectivity of mouse Nats toward common NAT
      substrates. In the present study, Nat1*, Nat2*8, and Nat3* were expressed in COS
      1 cells, and their substrate selectivity was evaluated with various substrates.
      Under the conditions used, mouse Nat2 had 20-, 2.4-, and 5.4-fold higher
      catalytic activity for p-aminobenzoic acid, 5-aminosalicylic acid, and 2
      aminofluorene, respectively, than Nat1. Isoniazid N-acetylation was catalyzed
      only by mouse Nat1. For the substrates tested in this study, mouse Nat3 exhibited
      activity only toward 5-aminosalicylic acid and only at 1/20 the activity shown by
      Nat2. In addition, p-aminobenzoylglutamate, the first endogenous NAT substrate
      identified, was selective for mouse Nat2. These results further support the
      functional analogy of mouse Nat2 and human NAT1.

PMID- 9571234
TI  - Saccharomyces cerevisiae cells with defective spindle pole body outer plaques
      accomplish nuclear migration via half-bridge-organized microtubules.
AB  - Cnm67p, a novel yeast protein, localizes to the microtubule organizing center,
      the spindle pole body (SPB). Deletion of CNM67 (YNL225c) frequently results in
      spindle misorientation and impaired nuclear migration, leading to the generation
      of bi- and multinucleated cells (40%). Electron microscopy indicated that CNM67
      is required for proper formation of the SPB outer plaque, a structure that
      nucleates cytoplasmic (astral) microtubules. Interestingly, cytoplasmic
      microtubules that are essential for spindle orientation and nuclear migration are
      still present in cnm67Delta1 cells that lack a detectable outer plaque. These
      microtubules are attached to the SPB half- bridge throughout the cell cycle. This
      interaction presumably allows for low-efficiency nuclear migration and thus
      provides a rescue mechanism in the absence of a functional outer plaque. Although
      CNM67 is not strictly required for mitosis, it is essential for sporulation. Time
      lapse microscopy of cnm67Delta1 cells with green fluorescent protein (GFP)
      labeled nuclei indicated that CNM67 is dispensable for nuclear migration
      (congression) and nuclear fusion during conjugation. This is in agreement with
      previous data, indicating that cytoplasmic microtubules are organized by the half
      bridge during mating.

PMID- 9571235
TI  - Fascin, an actin-bundling protein, induces membrane protrusions and increases
      cell motility of epithelial cells.
AB  - Fascin is an actin-bundling protein that is found in membrane ruffles,
      microspikes, and stress fibers. The expression of fascin is greatly increased in
      many transformed cells, as well as in specialized normal cells including neuronal
      cells and antigen-presenting dendritic cells. A morphological characteristic
      common to these cells expressing high levels of fascin is the development of many
      membrane protrusions in which fascin is predominantly present. To examine whether
      fascin contributes to the alterations in microfilament organization at the cell
      periphery, we have expressed fascin in LLC-PK1 epithelial cells to levels as high
      as those found in transformed cells and in specialized normal cells. Expression
      of fascin results in large changes in morphology, the actin cytoskeleton, and
      cell motility: fascin-transfected cells form an increased number of longer and
      thicker microvilli on apical surfaces, extend lamellipodia-like structures at
      basolateral surfaces, and show disorganization of cell-cell contacts. Cell
      migration activity is increased by 8-17 times when assayed by modified Boyden
      chamber. Microinjection of a fascin protein into LLC-PK1 cells causes similar
      morphological alterations including the induction of lamellipodia at basolateral
      surfaces and formation of an increased number of microvilli on apical surfaces.
      Furthermore, microinjection of fascin into REF-52 cells, normal fibroblasts,
      induces the formation of many lamellipodia at all regions of cell periphery.
      These results together suggest that fascin is directly responsible for membrane
      protrusions through reorganization of the microfilament cytoskeleton at the cell
      periphery.

PMID- 9571236
TI  - Phosphorothioate antisense oligonucleotides induce the formation of nuclear
      bodies.
AB  - Antisense oligonucleotides are powerful tools for the in vivo regulation of gene
      expression. We have characterized the intracellular distribution of fluorescently
      tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under
      conditions in which PS-ONs have the potential to display antisense activity.
      Under these conditions PS-ONs predominantly localized to the cell nucleus where
      they accumulated in 20-30 bright spherical foci designated phosphorothioate
      bodies (PS bodies), which were set against a diffuse nucleoplasmic population
      excluding nucleoli. PS bodies are nuclear structures that formed in cells after
      PS-ON delivery by transfection agents or microinjection but were observed
      irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies
      corresponded to electron-dense structures of 150-300 nm diameter and resembled
      nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The
      environment of a living cell was required for the de novo formation of PS bodies,
      which occurred within minutes after the introduction of PS-ONs. PS bodies were
      stable entities that underwent noticeable reorganization only during mitosis.
      Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools
      in the daughter nuclei. In situ fractionation demonstrated an association of PS
      ONs with the nuclear matrix. Taken together, our data provide evidence for the
      formation of a nuclear body in cells after introduction of phosphorothioate
      oligodeoxynucleotides.

PMID- 9571238
TI  - Nuclear ferritin protects DNA from UV damage in corneal epithelial cells.
AB  - Previously, we identified the heavy chain of ferritin as a developmentally
      regulated nuclear protein of embryonic chicken corneal epithelial cells. The
      nuclear ferritin is assembled into a supramolecular form indistinguishable from
      the cytoplasmic form of ferritin found in other cell types and thus most likely
      has iron-sequestering capabilities. Free iron, via the Fenton reaction, is known
      to exacerbate UV-induced and other oxidative damage to cellular components,
      including DNA. Since corneal epithelial cells are constantly exposed to UV light,
      we hypothesized that the nuclear ferritin might protect the DNA of these cells
      from free radical damage. To test this possibility, primary cultures of cells
      from corneal epithelium and stroma, and from skin epithelium and stroma, were UV
      irradiated, and DNA strand breaks were detected by an in situ 3'-end labeling
      method. Corneal epithelial cells without nuclear ferritin were also examined. We
      observed that the corneal epithelial cells with nuclear ferritin had
      significantly less DNA breakage than other cell types examined. Furthermore,
      increasing the iron concentration of the culture medium exacerbated the
      generation of UV-induced DNA strand breaks in corneal and skin fibroblasts, but
      not in the corneal epithelial cells. Most convincingly, corneal epithelial cells
      in which the expression of nuclear ferritin was inhibited became much more
      susceptible to UV-induced DNA damage. Therefore, it seems that corneal epithelial
      cells have evolved a novel, nuclear ferritin-based mechanism for protecting their
      DNA against UV damage.

PMID- 9571237
TI  - Coiled bodies and U2 snRNA genes adjacent to coiled bodies are enriched in
      factors required for snRNA transcription.
AB  - A significant percentage of the gene clusters that contain the human genes for U1
      small nuclear RNA (snRNA) or for U2 snRNA have been found associated with small
      nuclear domains, known as coiled bodies. We show here, by immunofluorescent
      labeling of human cells, that coiled bodies are enriched in factors required for
      the transcription of these snRNA genes. The 45-kDa gamma-subunit of the
      transcription factor, proximal element sequence-binding transcription factor
      (PTF), which is specific for the snRNA genes, was found in high concentrations in
      coiled bodies, along with the general transcription factor TATA-box binding
      protein and a subset of RNA polymerase II. We show that the transcription factors
      and RNA polymerase II are concentrated in irregularly shaped domains that not
      only overlap with coiled bodies but also extend to their immediate surroundings.
      Fluorescent in situ hybridization showed that these domains can overlap with U2
      snRNA genes adjacent to coiled bodies. In addition, we found the domains to
      contain newly synthesized RNA, visualized by 5-bromo-uridine triphosphate
      labeling. Our data suggest that coiled bodies are involved in the expression of
      snRNA genes, which leads us to propose the model that coiled bodies are
      associated with snRNA genes to facilitate and regulate their transcription. These
      findings point to a general principle of higher order organization of gene
      expression in the nucleus.

PMID- 9571239
TI  - Induction of exocytosis from permeabilized mast cells by the guanosine
      triphosphatases Rac and Cdc42.
AB  - We applied recombinant forms of the Rho-related small guanosine triphosphatases
      (GTPases) Rac2 and Cdc42/G25K to permeabilized mast cells to test their ability
      to regulate exocytotic secretion. Mast cells permeabilized with streptolysin-O
      leak soluble (cytosol) proteins over a period of 5 min and become refractory to
      stimulation by Ca2+ and guanosine triphosphate (GTP)gammaS over about 20-30 min.
      This loss of sensitivity is likely to be due to loss of key regulatory proteins
      that are normally tethered at intracellular locations. Exogenous proteins that
      retard this loss of sensitivity to stimulation may be similar, if not identical,
      to those secretory regulators that are lost. Recombinant Rac and Cdc42/G25K,
      preactivated by binding GTPgammaS, retard the loss of sensitivity (run-down) and,
      more importantly, enable secretion to be stimulated by Ca2+ alone. Investigation
      of the concentration dependence of each of these two GTPases applied individually
      to the permeabilized cells, and of Cdc42/G25K applied in the presence of an
      optimal concentration of Rac2, has provided evidence for a shared effector
      pathway and also a second effector pathway activated by Cdc42/G25K alone.
      Dominant negative mutant (N17) forms of Rac2 and Cdc42/G25K inhibit secretion
      induced by Ca2+ and GTPgammaS. Our data suggest that Rac2 and Cdc42 should be
      considered as candidates for GE, GTPases that mediate exocytosis in cells of
      hematopoeitic origin.

PMID- 9571240
TI  - Fission yeast Ste9, a homolog of Hct1/Cdh1 and Fizzy-related, is a novel negative
      regulator of cell cycle progression during G1-phase.
AB  - When proliferating fission yeast cells are exposed to nitrogen starvation, they
      initiate conjugation and differentiate into ascospores. Cell cycle arrest in the
      G1-phase is one of the prerequisites for cell differentiation, because
      conjugation occurs only in the pre-Start G1-phase. The role of ste9(+) in the
      cell cycle progression was investigated. Ste9 is a WD-repeat protein that is
      highly homologous to Hct1/Cdh1 and Fizzy-related. The ste9 mutants were sterile
      because they were defective in cell cycle arrest in the G1-phase upon starvation.
      Sterility was partially suppressed by the mutation in cig2 that encoded the major
      G1/S cyclin. Although cells lacking Ste9 function grow normally, the ste9
      mutation was synthetically lethal with the wee1 mutation. In the double mutants
      of ste9 cdc10(ts), cells arrested in G1-phase at the restrictive temperature, but
      the level of mitotic cyclin (Cdc13) did not decrease. In these cells, abortive
      mitosis occurred from the pre-Start G1-phase. Overexpression of Ste9 decreased
      the Cdc13 protein level and the H1-histone kinase activity. In these cells,
      mitosis was inhibited and an extra round of DNA replication occurred. Ste9
      regulates G1 progression possibly by controlling the amount of the mitotic cyclin
      in the G1-phase.

PMID- 9571241
TI  - The yeast Saccharomyces cerevisiae contains two glutaredoxin genes that are
      required for protection against reactive oxygen species.
AB  - Glutaredoxins are small heat-stable proteins that act as glutathione-dependent
      disulfide oxidoreductases. Two genes, designated GRX1 and GRX2, which share 40
      52% identity and 61-76% similarity with glutaredoxins from bacterial and
      mammalian species, were identified in the yeast Saccharomyces cerevisiae. Strains
      deleted for both GRX1 and GRX2 were viable but lacked heat-stable oxidoreductase
      activity using beta-hydroxyethylene disulfide as a substrate. Surprisingly,
      despite the high degree of homology between Grx1 and Grx2 (64% identity), the
      grx1 mutant was unaffected in oxidoreductase activity, whereas the grx2 mutant
      displayed only 20% of the wild-type activity, indicating that Grx2 accounted for
      the majority of this activity in vivo. Expression analysis indicated that this
      difference in activity did not arise as a result of differential expression of
      GRX1 and GRX2. In addition, a grx1 mutant was sensitive to oxidative stress
      induced by the superoxide anion, whereas a strain that lacked GRX2 was sensitive
      to hydrogen peroxide. Sensitivity to oxidative stress was not attributable to
      altered glutathione metabolism or cellular redox state, which did not vary
      between these strains. The expression of both genes was similarly elevated under
      various stress conditions, including oxidative, osmotic, heat, and stationary
      phase growth. Thus, Grx1 and Grx2 function differently in the cell, and we
      suggest that glutaredoxins may act as one of the primary defenses against mixed
      disulfides formed following oxidative damage to proteins.

PMID- 9571242
TI  - Correlation of alpha-fetoprotein expression in normal hepatocytes during
      development with tyrosine phosphorylation and insulin receptor expression.
AB  - The molecular mechanism of hepatic cell growth and differentiation is ill
      defined. In the present study, we examined the putative role of tyrosine
      phosphorylation in normal rat liver development and in an in vitro model, the
      alpha-fetoprotein-producing (AFP+) and AFP-nonproducing (AFP-) clones of the McA
      RH 7777 rat hepatoma. We demonstrated in vivo and in vitro that the AFP+
      phenotype is clearly associated with enhanced tyrosine phosphorylation, as
      assessed by immunoblotting and flow cytometry. Moreover, immunoprecipitation of
      proteins with anti-phosphotyrosine antibody showed that normal fetal hepatocytes
      expressed the same phosphorylation pattern as stable AFP+ clones and likewise for
      adult hepatocytes and AFP- clones. The tyrosine phosphorylation of several
      proteins, including the beta-subunit of the insulin receptor, insulin receptor
      substrate-1, p85 regulatory subunit of phosphatidylinositol-3-kinase, and ras
      guanosine triphosphatase-activating protein, was observed in AFP+ clones, whereas
      the same proteins were not phosphorylated in AFP- clones. We also observed that
      fetal hepatocytes and the AFP+ clones express 4 times more of the insulin
      receptor beta-subunit compared with adult hepatocytes and AFP- clones and,
      accordingly, that these AFP+ clones were more responsive to exogenous insulin in
      terms of protein tyrosine phosphorylation. Finally, growth rate in cells of AFP+
      clones was higher than that measured in cells of AFP- clones, and inhibition of
      phosphatidylinositol-3-kinase by LY294002 and Wortmannin blocked insulin- and
      serum-stimulated DNA synthesis only in cells of AFP+ clones. These studies
      provide evidences in support of the hypothesis that signaling via insulin
      prevents hepatocyte differentiation by promoting fetal hepatocyte growth.

PMID- 9571243
TI  - Lumenal and transmembrane domains play a role in sorting type I membrane proteins
      on endocytic pathways.
AB  - Previous studies have shown that when the cytosolic domains of the type I
      membrane proteins TGN38 and lysosomal glycoprotein 120 (lgp120) are added to a
      variety of reporter molecules, the resultant chimeric molecules are localized to
      the trans-Golgi network (TGN) and to lysosomes, respectively. In the present
      study we expressed chimeric constructs of rat TGN38 and rat lgp120 in HeLa cells.
      We found that targeting information in the cytosolic domain of TGN38 could be
      overridden by the presence of the lumenal and transmembrane domains of lgp120. In
      contrast, the presence of the transmembrane and cytosolic domains of TGN38 was
      sufficient to deliver the lumenal domain of lgp120 to the trans-Golgi network. On
      the basis of steady-state localization of the various chimeras and antibody
      uptake experiments, we propose that there is a hierarchy of targeting information
      in each molecule contributing to sorting within the endocytic pathway. The
      lumenal and cytosolic domains of lgp120 contribute to sorting and delivery to
      lysosomes, whereas the transmembrane and cytosolic domains of TGN38 contribute to
      sorting and delivery to the trans-Golgi network.

PMID- 9571244
TI  - RGS-GAIP, a GTPase-activating protein for Galphai heterotrimeric G proteins, is
      located on clathrin-coated vesicles.
AB  - RGS-GAIP (Galpha-interacting protein) is a member of the RGS (regulator of G
      protein signaling) family of proteins that functions to down-regulate
      Galphai/Galphaq-linked signaling. GAIP is a GAP or guanosine triphosphatase
      activating protein that was initially discovered by virtue of its ability to bind
      to the heterotrimeric G protein Galphai3, which is found on both the plasma
      membrane (PM) and Golgi membranes. Previously, we demonstrated that, in contrast
      to most other GAPs, GAIP is membrane anchored and palmitoylated. In this work we
      used cell fractionation and immunocytochemistry to determine with what particular
      membranes GAIP is associated. In pituitary cells we found that GAIP fractionated
      with intracellular membranes, not the PM; by immunogold labeling GAIP was found
      on clathrin-coated buds or vesicles (CCVs) in the Golgi region. In rat liver GAIP
      was concentrated in vesicular carrier fractions; it was not found in either Golgi
      or PM-enriched fractions. By immunogold labeling it was detected on clathrin
      coated pits or CCVs located near the sinusoidal PM. These results suggest that
      GAIP may be associated with both TGN-derived and PM-derived CCVs. GAIP represents
      the first GAP found on CCVs or any other intracellular membranes. The presence of
      GAIP on CCVs suggests a model whereby a GAP is separated in space from its target
      G protein with the two coming into contact at the time of vesicle fusion.

PMID- 9571245
TI  - Effect of carbohydrate position on lysosomal transport of procathepsin L.
AB  - To study the role of carbohydrate in lysosomal protein transport, we engineered
      two novel glycosylation signals (Asn-X-Ser/Thr) into the cDNA of human
      procathepsin L, a lysosomal acid protease. We constructed six mutant cDNAs
      encoding glycosylation signals at mutant sites Asn-138, Asn-175, or both sites
      together, in the presence or absence of the wild-type Asn-204 site. We stably
      transfected wild-type and mutant cDNAs into NIH3T3 mouse fibroblasts and then
      used species-specific antibodies to determine the glycosylation status,
      phosphorylation, localization, and transport kinetics of recombinant human
      procathepsin L containing one, two, or three glycosylation sites. Both novel
      glycosylation sites were capable of being glycosylated, although Asn-175 was
      utilized only 30-50% of the time. Like the wild-type glycosylation at Asn-204,
      carbohydrates at Asn-138 and Asn-175 were completely sensitive to endoglycosidase
      H, and they were phosphorylated. Mutant proteins containing two carbohydrates
      were capable of being delivered to lysosomes, but there was not a consistent
      relationship between the efficiency of lysosomal delivery and carbohydrate
      content of the protein. Pulse-chase labeling revealed a unique biosynthetic
      pattern for proteins carrying the Asn-175 glycosylation sequence. Whereas wild
      type procathepsin L and mutants bearing carbohydrate at Asn-138 appeared in
      lysosomes by about 60 min, proteins with carbohydrate at Asn-175 were processed
      to a lysosome-like polypeptide within 15 min. Temperature shift, brefeldin A, and
      NH4Cl experiments suggested that the rapid processing did not occur in the
      endoplasmic reticulum and that Asn-175 mutants could interact with the mannose 6
      phosphate receptor. Taken together, our results are consistent with the
      interpretation that Asn-175 carbohydrate confers rapid transport to lysosomes. We
      may have identified a recognition domain in procathepsin L that is important for
      its interactions with the cellular transport machinery.

PMID- 9571246
TI  - The medial-Golgi ion pump Pmr1 supplies the yeast secretory pathway with Ca2+ and
      Mn2+ required for glycosylation, sorting, and endoplasmic reticulum-associated
      protein degradation.
AB  - The yeast Ca2+ adenosine triphosphatase Pmr1, located in medial-Golgi, has been
      implicated in intracellular transport of Ca2+ and Mn2+ ions. We show here that
      addition of Mn2+ greatly alleviates defects of pmr1 mutants in N-linked and O
      linked protein glycosylation. In contrast, accurate sorting of carboxypeptidase Y
      (CpY) to the vacuole requires a sufficient supply of intralumenal Ca2+. Most
      remarkably, pmr1 mutants are also unable to degrade CpY*, a misfolded soluble
      endoplasmic reticulum protein, and display phenotypes similar to mutants
      defective in the stress response to malfolded endoplasmic reticulum proteins.
      Growth inhibition of pmr1 mutants on Ca2+-deficient media is overcome by
      expression of other Ca2+ pumps, including a SERCA-type Ca2+ adenosine
      triphosphatase from rabbit, or by Vps10, a sorting receptor guiding non-native
      luminal proteins to the vacuole. Our analysis corroborates the dual function of
      Pmr1 in Ca2+ and Mn2+ transport and establishes a novel role of this secretory
      pathway pump in endoplasmic reticulum-associated processes.

PMID- 9571247
TI  - Histone H1 reduces the frequency of initiation in Xenopus egg extract by limiting
      the assembly of prereplication complexes on sperm chromatin.
AB  - Somatic histone H1 reduces both the rate and extent of DNA replication in Xenopus
      egg extract. We show here that H1 inhibits replication directly by reducing the
      number of replication forks, but not the rate of fork progression, in Xenopus
      sperm nuclei. Density substitution experiments demonstrate that those forks that
      are active in H1 nuclei elongate to form large tracts of fully replicated DNA,
      indicating that inhibition is due to a reduction in the frequency of initiation
      and not the rate or extent of elongation. The observation that H1 dramatically
      reduces the number of replication foci in sperm nuclei supports this view. The
      establishment of replication competent DNA in egg extract requires the assembly
      of prereplication complexes (pre-RCs) on sperm chromatin. H1 reduces binding of
      the pre-RC proteins, XOrc2, XCdc6, and XMcm3, to chromatin. Replication
      competence can be restored in these nuclei, however, only under conditions that
      promote the loss of H1 from chromatin and licensing of the DNA. Thus, H1 inhibits
      replication in egg extract by preventing the assembly of pre-RCs on sperm
      chromatin, thereby reducing the frequency of initiation. These data raise the
      interesting possibility that H1 plays a role in regulating replication origin use
      during Xenopus development.

PMID- 9571248
TI  - Endocytic clathrin-coated pit formation is independent of receptor
      internalization signal levels.
AB  - The mechanisms responsible for coated pit formation in cells remain unknown, but
      indirect evidence has argued both for and against a critical role of receptor
      cytoplasmic domains in the process. If the endocytic motifs of receptors are
      responsible for recruiting AP2 to the plasma membrane, thereby driving coated pit
      formation, then the level of constitutively internalized receptors at the
      membrane would be expected to govern the steady-state level of coated pits in
      cells. Here we directly test this hypothesis for broad classes of receptors
      containing three distinct constitutive internalization signals. Chimeric proteins
      consisting of an integral membrane reporter protein (Tac) coupled to cytoplasmic
      domains bearing tyrosine-, di-leucine-, or acidic cluster/casein kinase II-based
      internalization signals were overexpressed to levels that saturated the
      internalization pathway. Quantitative confocal immunofluorescence microscopy
      indicated that the number of plasma membrane clathrin-coated pits and the
      concentration of their structural components were invariant when comparing cells
      expressing saturating levels of the chimeric receptors to nonexpressing cells or
      to cells expressing only the Tac reporter lacking cytoplasmic internalization
      signals. Biochemical analysis showed that the distribution of coat proteins
      between assembled coated pits and soluble pools was also not altered by receptor
      overexpression. Finally, the cellular localizations of AP2 and AP1 were similarly
      unaffected. These results provide a clear indication that receptor endocytic
      signals do not determine coated pit levels by directly recruiting AP2 molecules.
      Rather, the findings support a model in which coated pit formation proceeds
      through recruitment and activation of AP2, likely through a limited number of
      regulated docking sites that act independently of endocytic signals.

PMID- 9571249
TI  - A role for katanin-mediated axonemal severing during Chlamydomonas
      deflagellation.
AB  - Deflagellation of Chlamydomonas reinhardtii, and other flagellated and ciliated
      cells, is a highly specific process that involves signal-induced severing of the
      outer doublet microtubules at a precise site in the transition region between the
      axoneme and basal body. Although the machinery of deflagellation is activated by
      Ca2+, the mechanism of microtubule severing is unknown. Severing of singlet
      microtubules has been observed in vitro to be catalyzed by katanin, a
      heterodimeric adenosine triphosphatase that can remove tubulin subunits from the
      walls of stable microtubules. We found that purified katanin induced an ATP
      dependent severing of the Chlamydomonas axoneme. Using Western blot analysis and
      indirect immunofluorescence, we demonstrate that Chlamydomonas expresses a
      protein that is recognized by an anti-human katanin antibody and that this
      protein is localized, at least in part, to the basal body complex. Using an in
      vitro severing assay, we show that the protein(s) responsible for Ca2+-activated
      outer doublet severing purify with the flagellar-basal body complex. Furthermore,
      deflagellation of purified flagellar-basal body complexes is significantly
      blocked by the anti-katanin antibody. Taken together, these data suggest that a
      katanin-like mechanism may mediate the severing of the outer doublet microtubules
      during Chlamydomonas deflagellation.

PMID- 9571250
TI  - Phosphatidylinositol 3-kinase-mediated endocytosis of renal Na+, K+-ATPase alpha
      subunit in response to dopamine.
AB  - Dopamine (DA) inhibition of Na+,K+-ATPase in proximal tubule cells is associated
      with increased endocytosis of its alpha and beta subunits into early and late
      endosomes via a clathrin vesicle-dependent pathway. In this report we evaluated
      intracellular signals that could trigger this mechanism, specifically the role of
      phosphatidylinositol 3-kinase (PI 3-K), the activation of which initiates
      vesicular trafficking and targeting of proteins to specific cell compartments. DA
      stimulated PI 3-K activity in a time- and dose-dependent manner, and this effect
      was markedly blunted by wortmannin and LY 294002. Endocytosis of the Na+,K+
      ATPase alpha subunit in response to DA was also inhibited in dose-dependent
      manner by wortmannin and LY 294002. Activation of PI 3-K generally occurs by
      association with tyrosine kinase receptors. However, in this study
      immunoprecipitation with a phosphotyrosine antibody did not reveal PI 3-K
      activity. DA-stimulated endocytosis of Na+, K+-ATPase alpha subunits required
      protein kinase C, and the ability of DA to stimulate PI 3-K was blocked by
      specific protein kinase C inhibitors. Activation of PI 3-K is mediated via the D1
      receptor subtype and the sequential activation of phospholipase A2, arachidonic
      acid, and protein kinase C. The results indicate a key role for activation of PI
      3-K in the endocytic sequence that leads to internalization of Na+,K+-ATPase
      alpha subunits in response to DA, and suggest a mechanism for the participation
      of protein kinase C in this process.

PMID- 9571252
TI  - Emergence of multidrug-resistant Salmonella enterica serotype typhimurium DT104
      infections in the United States.
AB  - BACKGROUND: Strains of salmonella that are resistant to antimicrobial agents have
      become a worldwide health problem. A distinct strain of Salmonella enterica
      serotype typhimurium, known as definitive type 104 (DT104), is resistant to
      ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline and has
      become a major cause of illness in humans and animals in Europe, especially the
      United Kingdom. METHODS: To characterize typhimurium DT104 infections in the
      United States, we analyzed data collected by local and state health departments
      and public health laboratories between 1979 and 1996 in national surveys of the
      antimicrobial-drug resistance of salmonella. Selected typhimurium isolates with
      the five-drug pattern of resistance were phage typed. RESULTS: The prevalence of
      typhimurium isolates with the five-drug pattern of resistance increased from 0.6
      percent in 1979-1980 to 34 percent in 1996. In 1994-1995, such isolates were
      identified in samples from 36 of the 46 surveillance sites (78 percent). Thirty
      nine of 43 typhimurium isolates with the five-drug pattern of resistance
      identified in 1994-1995 and 1996 were phage type DT104 or a closely related phage
      type. CONCLUSIONS: Multidrug-resistant typhimurium DT104 has become a widespread
      pathogen in the United States. More prudent use of antimicrobial agents in farm
      animals and more effective disease prevention on farms are necessary to reduce
      the dissemination of multidrug-resistant typhimurium DT104 and to slow the
      emergence of resistance to additional agents in this and other strains of
      salmonella.

PMID- 9571251
TI  - Rho1p-Bni1p-Spa2p interactions: implication in localization of Bni1p at the bud
      site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae.
AB  - Rho1p is a yeast homolog of mammalian RhoA small GTP-binding protein. Rho1p is
      localized at the growth sites and required for bud formation. We have recently
      shown that Bni1p is a potential target of Rho1p and that Bni1p regulates
      reorganization of the actin cytoskeleton through interactions with profilin, an
      actin monomer-binding protein. Using the yeast two-hybrid screening system, we
      cloned a gene encoding a protein that interacted with Bni1p. This protein, Spa2p,
      was known to be localized at the bud tip and to be implicated in the
      establishment of cell polarity. The C-terminal 254 amino acid region of Spa2p,
      Spa2p(1213-1466), directly bound to a 162-amino acid region of Bni1p, Bni1p(826
      987). Genetic analyses revealed that both the bni1 and spa2 mutations showed
      synthetic lethal interactions with mutations in the genes encoding components of
      the Pkc1p-mitogen-activated protein kinase pathway, in which Pkc1p is another
      target of Rho1p. Immunofluorescence microscopic analysis showed that Bni1p was
      localized at the bud tip in wild-type cells. However, in the spa2 mutant, Bni1p
      was not localized at the bud tip and instead localized diffusely in the
      cytoplasm. A mutant Bni1p, which lacked the Rho1p-binding region, also failed to
      be localized at the bud tip. These results indicate that both Rho1p and Spa2p are
      involved in the localization of Bni1p at the growth sites where Rho1p regulates
      reorganization of the actin cytoskeleton through Bni1p.

PMID- 9571253
TI  - Risk of cancer among offspring of childhood-cancer survivors. Association of the
      Nordic Cancer Registries and the Nordic Society of Paediatric Haematology and
      Oncology.
AB  - BACKGROUND: Increasing numbers of children with cancer survive and reach
      reproductive age. However, the risk of cancer (other than retinoblastoma) in the
      offspring of survivors of childhood and adolescent cancer is uncertain. METHODS:
      Using data from national cancer and birth registries, we assessed the risk of
      cancer among 5847 offspring of 14,652 survivors of cancer in childhood or
      adolescence diagnosed since the 1940s and 1950s in Denmark, Finland, Iceland,
      Norway, and Sweden. The offspring were followed up for a diagnosis of cancer for
      86,780 person-years, and standardized incidence ratios were calculated. RESULTS:
      Among the 5847 offspring, 44 malignant neoplasms were diagnosed (standardized
      incidence ratio, 2.6; 95 percent confidence interval, 1.9 to 3.5). There were 17
      retinoblastomas, yielding a standardized incidence ratio of 37. There were 27
      neoplasms other than retinoblastoma (standardized incidence ratio, 1.6; 95
      percent confidence interval, 1.1 to 2.4). The second most common primary site of
      cancer among the offspring was the brain and nervous system, in which eight
      tumors were observed (standardized incidence ratio, 2.0; 95 percent confidence
      interval, 0.9 to 3.9.) There were between zero and four apparently sporadic cases
      of cancer in other primary sites among the offspring. Excluding 4 likely cases of
      hereditary cancer and 2 subsequent cancers among the offspring with hereditary
      retinoblastoma, there were 22 sporadic cancers, for a standardized incidence
      ratio of 1.3 (95 percent confidence interval, 0.8 to 2.0). CONCLUSIONS: There is
      no evidence of a significantly increased risk of nonhereditary cancer among the
      offspring of survivors of cancer in childhood.

PMID- 9571254
TI  - Failure of cytarabine in progressive multifocal leukoencephalopathy associated
      with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy affects about 4 percent of
      patients with the acquired immunodeficiency syndrome (AIDS), and survival after
      the diagnosis of leukoencephalopathy averages only about three months. There have
      been anecdotal reports of improvement but no controlled trials of therapy with
      antiretroviral treatment plus intravenous or intrathecal cytarabine. METHODS: In
      this multicenter trial, 57 patients with human immunodeficiency virus (HIV)
      infection and biopsy-confirmed progressive multifocal leukoencephalopathy were
      randomly assigned to receive one of three treatments: antiretroviral therapy
      alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral
      therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks,
      active treatment was given for 24 weeks. For most patients, antiretroviral
      therapy consisted of zidovudine plus either didanosine or stavudine. RESULTS: At
      the time of the last analysis, 14 patients in each treatment group had died, and
      there were no significant differences in survival among the three groups (P=0.85
      by the log-rank test). The median survival times (11, 8, and 15 weeks,
      respectively) were similar to those in previous studies. Only seven patients
      completed the 24 weeks of treatment. Anemia and thrombocytopenia were more
      frequent in patients who received antiretroviral therapy in combination with
      intravenous cytarabine than in the other groups. CONCLUSIONS: Cytarabine
      administered either intravenously or intrathecally does not improve the prognosis
      of HIV-infected patients with progressive multifocal leukoencephalopathy who are
      treated with the antiretroviral agents we used, nor does high-dose antiretroviral
      therapy alone appear to improve survival over that reported in untreated
      patients.

PMID- 9571255
TI  - Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the
      glutamate dehydrogenase gene.
AB  - BACKGROUND: A new form of congenital hyperinsulinism characterized by
      hypoglycemia and hyperammonemia was described recently. We hypothesized that this
      syndrome of hyperinsulinism and hyperammonemia was caused by excessive activity
      of glutamate dehydrogenase, which oxidizes glutamate to alpha-ketoglutarate and
      which is a potential regulator of insulin secretion in pancreatic beta cells and
      of ureagenesis in the liver. METHODS: We measured glutamate dehydrogenase
      activity in lymphoblasts from eight unrelated children with the hyperinsulinism
      hyperammonemia syndrome: six with sporadic cases and two with familial cases. We
      identified mutations in the glutamate dehydrogenase gene by sequencing glutamate
      dehydrogenase complementary DNA prepared from lymphoblast messenger RNA. Site
      directed mutagenesis was used to express the mutations in COS-7 cells. RESULTS:
      The sensitivity of glutamate dehydrogenase to inhibition by guanosine 5'
      triphosphate was a quarter of the normal level in the patients with sporadic
      hyperinsulinism-hyperammonemia syndrome and half the normal level in patients
      with familial cases and their affected relatives, findings consistent with
      overactivity of the enzyme. These differences in enzyme insensitivity correlated
      with differences in the severity of hypoglycemia in the two groups. All eight
      children were heterozygous for the wild-type allele and had a mutation in the
      proposed allosteric domain of the enzyme. Four different mutations were
      identified in the six patients with sporadic cases; the two patients with
      familial cases shared a fifth mutation. In two clones of COS-7 cells transfected
      with the mutant sequence from one patient, the sensitivity of the enzyme to
      guanosine 5'-triphosphate was reduced, findings similar to those in the child's
      lymphoblasts. CONCLUSIONS: The hyperinsulinism-hyperammonemia syndrome is caused
      by mutations in the glutamate dehydrogenase gene that impair the control of
      enzyme activity.

PMID- 9571256
TI  - Images in clinical medicine. Cervical-disk herniation.

PMID- 9571257
TI  - Antibodies to DNA.

PMID- 9571258
TI  - Evaluation of patients with palpitations.

PMID- 9571259
TI  - Private arsenals and public peril.

PMID- 9571260
TI  - Multidrug resistance--a sign of the times.

PMID- 9571261
TI  - Progressive multifocal leukoencephalopathy--progress made and lessons relearned.

PMID- 9571262
TI  - Masked monitoring in clinical trials--blind stupidity?

PMID- 9571263
TI  - CLAO membership: more valuable than ever.

PMID- 9571264
TI  - Mydriasis from inadvertent topical application of naphazoline hydrochloride
      (Opcon-A, Bausch & Lomb)

PMID- 9571265
TI  - Special-effect contact lenses.

PMID- 9571266
TI  - Masking of irregular corneal topography with contact lenses.
AB  - PURPOSE: We examined the effectiveness of various types of contact lenses in
      masking irregular corneal topography using videokeratoscopy, residual
      aberrations, and measurement of visual acuity. METHODS: Thirteen subjects with
      differing degrees of keratoconus were recruited. Four types of soft lenses were
      used that varied in both thickness and water content, along with a rigid gas
      permeable (RGP) and a flexible gas permeable contact lens. RESULTS: RGP contact
      lenses provided the best visual acuity and the least residual aberrations.
      Flexible gas permeable lenses showed a reasonable masking of corneal distortion
      but did not provide the expected improvement in visual acuity. Soft contact
      lenses provided marginally better visual acuity than spectacle correction, but
      the level of residual aberrations was still high, even for relatively thick soft
      lenses (up to 0.2 mm). A significant correlation existed between the regularity
      of the front surface of the contact lenses on the eye and visual acuity in low
      illumination. CONCLUSIONS: Among the currently available contact lens materials,
      RGP lenses provide the best visual performance for subjects with keratoconus.

PMID- 9571267
TI  - The effectiveness of several current soft contact lens care systems against
      Aspergillus.
AB  - PURPOSE: Fungal contamination of contact lenses is a common occurrence. In this
      study, we tested the effectiveness of currently used soft contact lens care
      systems against Aspergillus fumigatus. METHODS: We prepared and added 100 microL
      inoculums of 1 x 10(6) colony forming units/mL to each test solution. We exposed
      fungi to disinfectant for 4, 6, and 8 hours or to cleaning solution for 1 minute.
      We then diluted and plated the samples. After 48 hours, we counted the number of
      colony forming units. RESULTS: We represented the cleaning agent results as a
      percentage of the number of colony forming units found in the control at the same
      exposure period: Quick CARE Starting Solution--0%, MiraFlow--12%, Opti-Free Daily
      Cleaner--41%, and PureEyes Cleaner/Rinse--82%. We calculated the percent control
      for 4, 6 and 8 hour exposures for each disinfecting solution: Opti-One--197%,
      163%, and 109%; Quick-CARE Finishing Solution--84.6%, 55%, and 31%; ReNu--97.4%,
      17%, and 4%; Complete--10%, 1%, and 0.4%; PureEyes Disinfectant/Soaking Solution-
      0%, 0%, and 0%; and Hydrocare--0%, 0%, and 0%. CONCLUSION: This study of contact
      lens care systems provides a direct comparison of their effectiveness against the
      same strain of Aspergillus. The results allow practitioners to select the
      appropriate care system for each patient.

PMID- 9571268
TI  - Defining the physiologically normal coating and pathological deposit: an analysis
      of sulfur-containing moieties and pellicle thickness on hydrogel contact lenses.
AB  - PURPOSE: Historically, biochemical studies of the interaction between tears and
      hydrogel contact lenses have not been coordinated with the study of the
      morphological ultrastructure of the phenomena. Moreover, terms that have distinct
      and different meanings--pellicle, coating, deposit, and biofilm--have been used
      interchangeably and often incorrectly when applied within the context of the
      general field of contact lens biotechnology to describe the tear-polymer
      interaction. We describe our elucidation of morphological and elemental
      characteristics of the normal pellicle that forms on the lens surface and urge
      standard use of the word "pellicle" to specify this entity. METHODS: Fourteen
      worn hydrogel lenses (8 Group 1 and 6 Group 4 lenses according to the FDA
      classification) were rinsed, quartered, and fixed or dried, depending on the
      analysis to be performed. Scanning electron microscopy (SEM) was used to examine
      the morphology of the pellicle and quantify its thickness. X-ray analysis was
      used to detect elements associated with the anterior, central, and posterior
      portions of the lenses and their relative distribution. RESULTS: A distinctive
      morphological pellicle ranging from 0.1 to 8.6 microns was present on 12 of the
      14 lenses. The pellicle was thicker on the Group 4 lenses than on the Group 1
      lenses (P < 0.003). However, the pellicle on Group 1 lenses became thicker with
      increasing lens age (P < 0.02), but not as thick as on Group 4 lenses.
      Morphologically distinct lipid or jelly bump deposits were observed at the
      surface of both lenses from a single patient wearing 2 week old Group 4 lenses.
      Eleven lenses had sulfur-bearing tear components on the anterior zone. Sulfur was
      deposited within the matrix of nine lenses. The sulfur containing moieties were
      more prevalent on Group 4 lenses (P < 0.002). More sulfur was assayed on older
      lenses (P < 0.004). The anterior lens zone had more sulfur-bearing tear
      components than did the posterior or center zones (P < 0.05). CONCLUSIONS: The
      physiologically normal pellicle is a distinct morphological entity covering the
      anterior lens surface. Abnormal deposits such as the discrete microgel region,
      known as jelly bumps, are not part of the physiologically normal pellicle at the
      anterior lens surface and have the potential to induce pathology. Sulfur
      containing moieties within the matrix may represent the breakdown of large
      proteins and mucoproteins or intact proteins, as well as contaminants such as
      cosmetics and environmental pollutants. It is also possible that entire small
      proteins, such as lysozyme, impregnate the matrix. The moieties that become
      entrapped within the matrix or rigidly adhere to the matrix should be considered
      true deposits.

PMID- 9571269
TI  - Fitting characteristics of Dailies daily disposable hydrogel contact lenses.
AB  - PURPOSE: We evaluated the fitting characteristics of nelfilcon A contact lenses
      to determine the optimal time for judging lens performance during trial fitting.
      METHODS: Twenty subjects wore a pair of DAILIES (daily disposable soft lenses)
      for 8 hours. A slit lamp camera was used to videotape lens fit every 5 minutes
      during the first 30 minutes and at 8 hours. Lens movement and centration were
      measured in 0.1 mm increments by a single observer. RESULTS: Lens movement
      decreased significantly during the first 30 minutes of wearing time (P < 0.001).
      Mean lens movement measured 0.31 mm initially, decreased to 0.17 mm at 25 minutes
      of wear, and then increased to 0.33 mm at 8 hours (P < 0.001). At 5 minutes, 93%
      of eyes showed lens movement within 0.2 mm of the value at 8 hours. Lens
      centration did not change during the first 30 minutes of wear and was comparable
      to centration measured at 8 hours. CONCLUSIONS: During trial fitting, the optimal
      time for evaluating movement of nelfilcon A contact lenses is during the first 5
      minutes of wear. Lens movement measured at 8 hours will likely be greater than
      lens movement measured 10 to 30 minutes after insertion.

PMID- 9571271
TI  - Changes in intraocular pressure due to cycloplegia.
AB  - PURPOSE: We studied intraocular pressure (IOP) in a group of healthy myopic
      subjects before and after administration of chlorhydrate cyclopentolate 1%.
      METHODS: We measured the IOP before administration and at 15, 30, 45, 60, and 300
      minutes and 24 hours after administration. RESULTS: The rise in IOP at 15 and 300
      minutes was not significant (P > 0.05), while the rise at 30, 45, and 60 minutes
      was significant (P < 0.05). The increase reached its maximum at 45 minutes. At
      300 minutes, the increase was almost completely overcome and was not significant.
      At 24 hours, the pressure had returned to initial values. CONCLUSIONS:
      Cyclopentolate represents a valuable aid in performing retinoscopy in healthy
      subjects who have an anterior chamber with adequate depth and an open angle.

PMID- 9571270
TI  - Evaluation of night vision disturbances in contact lens wearers.
AB  - PURPOSE: We quantitatively recorded and evaluated night vision disturbances with
      physiologically dilated pupils. We compared the amount of image degradation
      experienced in eyes wearing spherical soft contact lenses with the amount of
      image degradation experienced by subjects wearing spectacles. METHODS: We
      prospectively evaluated 69 eyes from 35 myopic subjects with no ocular pathology.
      The subjects ranged in age from 22 to 35 years. We designed a test to
      quantitatively record image degradation with physiologically dilated pupils in
      scotopic conditions of dim ambient light. Previously, we have shown that this
      test accurately measures image degradation. We used this test to compare image
      degradation between new spherical soft contact lens and spectacle correction.
      Hyperopes and eyes with greater than 1.50 D of astigmatism were excluded.
      RESULTS: Adequately correcting myopic refractive error decreased recorded image
      degradation (P < or = 0.0001). There was no significant difference in the amount
      of image degradation between spectacle trial frames and new spherical soft
      contact lenses (P < or = 0.2885). CONCLUSIONS: Our test offers an objective
      method of assessing night vision disturbances in contact lens wearers. Our
      results suggest that image degradation, which may contribute to the sensation of
      glare experienced by some patients, is influenced equally by contact lens and
      spectacle correction.

PMID- 9571272
TI  - Refractive change following pterygium surgery.
AB  - PURPOSE: We conducted a prospective study of patients with primary pterygia to
      analyze surgically-induced astigmatic changes following pterygium surgery and
      their relation to pterygium morphology and size. METHODS: One hundred twenty
      three eyes of 123 adult patients with primary pterygia were evaluated. Pterygium
      was graded according to morphology and the extent of corneal encroachment.
      Manifest refraction was performed preoperatively and at 1, 3, and 6 months
      postoperatively. Patients underwent either the bare sclera technique of pterygium
      excision or conjunctival grafting. Surgery was performed by one surgeon. Olsen's
      method of vector decomposition was used to analyze surgically-induced
      astigmatism. RESULTS: The mean magnitude of preoperative astigmatism was 0.99 D,
      with vector decomposition revealing a relative flattening of the cornea in the
      horizontal meridian. Astigmatism of 1.00 D or more was seen when the pterygium
      exceeded 3.5 mm beyond the limbus. Postoperatively, a steepening of the cornea in
      the horizontal meridian was demonstrated, the magnitude of which was related to
      pterygium size (P = 0.0001). ANOVA testing showed no significant difference (P >
      0.05) when pterygia were divided according to morphology. CONCLUSIONS: This study
      confirms that pterygium excision induces a reversal of pterygium-related corneal
      flattening. A strong correlation was also found between the horizontal extent of
      pterygium encroachment and astigmatic change following surgery.

PMID- 9571273
TI  - An alternative approach to bandage contact lenses.
AB  - PURPOSE: Therapeutic bandage contact lenses have been used in the management of a
      variety of corneal and anterior segment disorders. However, clinical experience
      with the therapeutic use of disposable contact lenses is limited. The present
      study was designed to evaluate the efficacy of disposable contact lenses as
      bandage lenses in anterior segment disorders. METHODS: We fit 45 patients who had
      various corneal and anterior segment disorders with disposable contact lenses
      (42% etafilcon A and 58% water content). We used this lens as a healing and
      surgical adjunct and for structural support and symptomatic relief. Patients were
      followed for a minimum period of 3 months. Therapeutic efficacy and complications
      were evaluated. RESULTS: Eighty-two percent of patients were fit successfully.
      Ninety-one percent of the successfully fit patients were therapeutic successes.
      Disposable lenses were found to be very useful in the management of epithelial
      abnormalities and as surgical adjuncts. Dry eye was the most frequent cause of
      contact lens associated therapeutic failure. Complications included contact lens
      deposits, lens loss, and corneal neovascularization. CONCLUSIONS: The use of
      disposable lenses was most effective in conditions requiring short-term lens use
      where one to two lens applications were sufficient to allow healing, making
      disposable lenses a very convenient and cost-effective alternative to
      conventional therapeutic bandage contact lenses. For reasons of cost, disposable
      lenses were not a viable alternative in conditions requiring therapeutic lens use
      for long periods of time.

PMID- 9571274
TI  - Delivery of trifluridine to human cornea and aqueous using collagen shields.
AB  - PURPOSE: We investigated the ability of collagen shields to deliver trifluridine
      (trifluorothymidine [TFT]) to human cornea and aqueous humor. METHODS: 24-hour
      porcine collagen shields were soaked in commercially prepared TFT (Viroptic).
      Patients undergoing penetrating keratoplasty wore a pre-soaked collagen shield
      for at least 30 minutes preoperatively. Control patients received drops of TFT
      only. Cornea and aqueous samples were obtained. TFT levels were measured using
      high performance liquid chromatography. RESULTS: Among the four patients with
      intact corneal epithelium, TFT was detected in only one patient (0.13 microgram/g
      in the aqueous). In seven patients with poor epithelium, corneal levels ranged
      from 0 to 635.34 micrograms/g, and aqueous levels ranged from 0.06 to 11.17
      micrograms/g. CONCLUSIONS: Collagen shields do not enhance delivery of TFT to
      corneas with intact epithelium. In corneas with poor epithelium, drug penetration
      was higher but variable. The role of collagen shields as a drug delivery system
      for the treatment of herpes simplex keratitis remains to be determined.

PMID- 9571275
TI  - The use of occluding tinted contact lenses.
AB  - PURPOSE: We explored the clinical issues surrounding the use of tinted contact
      lenses for vision occlusion in cases of debilitating vision disturbance, such as
      intractable diplopia. METHODS: We report the results with four patients fit with
      occluding tinted contact lenses. RESULTS: Vision occlusion by contact lenses
      provided a suitable comfortable occlusion method with improved cosmesis compared
      to occlusion by spectacles. Lens parameters and tint specifications were ordered
      for each patient. Correct lens care and handling were necessary to avoid contact
      lens related ocular inflammation. CONCLUSION: Provided that lens care is
      satisfactory and the patient does not have unreasonable expectations, a tinted
      contact lens can be a useful alternative to a covered spectacle lens or eye patch
      when occluding one eye, such as in cases of intractable diplopia, severe vision
      distortion, or intolerable photophobia.

PMID- 9571276
TI  - Three patients with the osteochondrodysplasia and hypertrichosis syndrome--Cantu
      syndrome.
AB  - Cantu syndrome is a rare condition whose main features are hypertrichosis,
      cardiac anomalies and wide ribs. Four children have been described and we now
      present details of a further three. The parents of one of these are first
      cousins, adding weight to Cantu's theory that the condition is an autosomal
      recessive disease.

PMID- 9571277
TI  - The cerebro-costo-mandibular syndrome: seven patients and review of the
      literature.
AB  - We report seven patients with the cerebro-costo-mandibular syndrome, a multiple
      congenital anomaly syndrome with, as the most distinctive features extreme
      micrognathia and abnormal rib development. Twice a parent to child transmission
      was found, compatible with autosomal dominant mode of inheritance. One of our
      patients presented with absence of the auditory canals and subluxation of the
      radial head, and another with choanal atresia, findings that have not been
      published previously. Longterm follow-up of some of the patients is described,
      and an overview of the literature is given.

PMID- 9571278
TI  - Goldberg-Shprintzen syndrome: report of a new family and review of the
      literature.
AB  - In 1981, Goldberg and Shprintzen described siblings with short-segment
      Hirschsprung disease, cleft palate, microcephaly, mild mental retardation, short
      stature and distinctive facial appearance. There have been several subsequent
      reports which broaden the phenotype. This paper describes a further family,
      reviews the literature and stresses the intra-familial variability.

PMID- 9571279
TI  - SHORT syndrome: distinctive radiographic features.

PMID- 9571280
TI  - A new lethal autosomal recessive skeletal dysplasia with associated dysmorphic
      features.
AB  - We report a fetus noted on routine ultrasonography at 21 weeks gestation to have
      a skeletal dysplasia with reduced ossification of shortened long bones and normal
      sized ribs. The consanguineous parents elected to continue the pregnancy and
      spontaneous labour occurred at 33 weeks gestation. The child died in the neonatal
      period. At necropsy, the main skeletal features were abnormal vertebrae with
      variation in shape and size, and ossification centres, short angulated long bones
      with distorted metaphyses and multiple abnormalities and fusions of the phalanges
      and metacarpals. In addition there was hydrops fetalis, a 'digit like' appendage
      overlying the left biceps muscle, a small chest with pulmonary hypoplasia and
      facial dysmorphism. In a subsequent pregnancy the fetus was noted at 13 weeks
      gestation to have nuchal translucency and bilaterally short femora. The fetus
      progressively developed hydrops fetalis and intrauterine death occurred at 22
      weeks gestation. Post mortem examination revealed features very similar to the
      previous sibling. We suggest that this a new lethal osteochondrodysplasia
      syndrome. Recurrence in female siblings and parents who are double first cousins,
      strongly indicate autosomal recessive inheritance.

PMID- 9571281
TI  - A unique lethal spondylocostal metaphyseal dysplasia: a case report.

PMID- 9571282
TI  - Syndactyly, micrognathia and skeletal anomalies: a new syndrome?
AB  - We report a fetus with micrognathia, cleft palate, polysyndactyly, brachycephaly
      and proximal radial hypoplasia. We believe the abnormalities represent a new
      syndrome not previously described.

PMID- 9571283
TI  - Central nervous system malformations, dense bones and facial dysmorphism: a new
      autosomal recessive syndrome.
AB  - We report a child with multiple congenital abnormalities which include complex
      central nervous system malformations, dense bones with wide irregular metaphyses,
      facial dysmorphic features and lethality. We suggest that the combination of
      abnormalities in the child could represent a new syndrome.

PMID- 9571284
TI  - The autosomal recessive congenital intrauterine infection-like syndrome of
      microcephaly, intracranial calcification, and CNS disease: report of another
      Bedouin family.
AB  - We describe a Bedouin family with the rare autosomal recessive infection-like
      syndrome of microcephaly, intracranial calcification and CNS disease that has so
      far been documented in only eight families including one from Kuwait. In the
      present family, the female proband had congenital microbrachycephaly, hypertonia,
      early-onset tonic-clonic seizures, a palpable liver and mild pulmonary stenosis.
      Follow-up examination of the girl identified delayed developmental milestones
      while head CT scan revealed partial agenesis of the corpus callosum, brain
      atrophy, dilated ventricles and scattered calcific foci in the caudate nuclei,
      the thalami, and the periventricular white matter. The possibility of
      intrauterine TORCH infection was excluded by the negative results of repeated
      immunovirology study and by the failure to recover viral inclusions in urine
      cultures. The proband had three apparently affected cousins with spasticity and
      CT findings of microcephaly and intracranial calcification. Other previously
      documented cases with the congenital intrauterine infection-like syndrome are
      reviewed.

PMID- 9571285
TI  - Cutis verticis gyrata-mental deficiency syndrome: report of a case with unusual
      neuroradiological findings.
AB  - The clinical and radiological features of a patient with Cutis Verticis Gyrata
      Mental Deficiency syndrome are reported. The clinical features of the patient
      included severe mental retardation, drug resistant epilepsy, short stature,
      microcephaly with multiple furrows on the scalp and normally growing overlying
      hair. He was blind with bilateral optic atrophy, multiple joint contractures and
      spastic tetraplegia. Skull X-ray showed thickened calvarial bones but other
      features of pachydermoperiostosis were absent. Brain MRI showed well developed,
      albeit small, frontal and anterior temporal lobes with a normal gray-white matter
      interface. The parietal and occipital cortex were atrophic with widening of the
      occipital horns (colpocephaly). The sylvian fissures were accentuated because of
      atrophic parietal operculae. The splenium of the corpus callosum was hypoplastic.
      There was atrophy of the cerebellar cortex. Contrary to the previously described
      cerebral cortical polymicrogyria in Cutis Verticis Gyrata-Mental Deficiency
      syndrome, there was no evidence to suggest any migration disorder in our patient.
      The present report highlights the clinico-radiological heterogeneity of the
      syndrome.

PMID- 9571286
TI  - Rapadilino syndrome--a non-Finnish case.
AB  - We report on a boy with RAPADILINO syndrome. Including this report seven children
      with this syndrome have been described. The patient developed a poikilodermatous
      skin rash, suggesting overlap with the Rothmund-Thompson syndrome.

PMID- 9571287
TI  - Cerebro-oculo-nasal syndrome: another case and review of the literature.
AB  - Cerebro-Oculo-Nasal syndrome; a new multiple congenital anomaly/mental
      retardation syndrome was first reported by Richieri-Costa and Guion-Almeida in
      1993 (Am J Med Genet 47:702-706) in two patients. To the best of our knowledge
      four additional cases have been reported. The main features of the syndrome are
      anophthalmia/microphthalmia, abnormal nares, and central nervous system
      anomalies. In this report, an additional sporadic case of this syndrome is
      presented. A 6-year-old girl from a non-consanguineous couple with normal
      prenatal growth parameters and retarded postnatal growth had anophthalmia,
      uplifted right nares with skin tag, and slight clefting at the tip of the nose,
      upper lip and gingiva. She also had a high-arched narrow palate, slightly low set
      ears, hypertelorism, a CNS defect and mental retardation. Additional findings
      were hypoplastic teeth with dental malocclusion, muscular hypotonia and midline
      hyperpigmentation over the anterior neck and the abdomen.

PMID- 9571288
TI  - XK aprosencephaly.
AB  - We report a baby with aprosencephaly, preaxial limb defect and ambiguous
      genitalia. This combination of abnormalities have been reported previously and
      constitute the XK aprosencephaly syndrome.

PMID- 9571289
TI  - Costello syndrome with acoustic neuroma and cataract. Is the Costello locus
      linked to neurofibromatosis type 2 on 22q?

PMID- 9571290
TI  - New findings in a patient with distal 13q-.

PMID- 9571291
TI  - A syndrome of a distinctive facies and normal neurology.

PMID- 9571292
TI  - Topographic EEG studies of mania.
AB  - QEEG findings from 39 hospitalized manic patients were accomplished after a drug
      free period and following pharmacotherapy with lithium or carbamazepine alone or
      lithium combined with carbamazepine, haloperidol or risperidone. A subsample of
      10 drug-free manic patients was compared with normal controls, which revealed
      lower qEEG amplitudes in the left anterior and midtemporal regions in the
      patients. Comparisons of drug therapies showed increased delta amplitudes and
      total power with lithium compared with carbamazepine. Increased fast frequencies
      were observed in the lithium and carbamazepine plus lithium groups compared with
      carbamazepine alone. Comparisons of the three drug combination groups revealed
      increased alpha and beta 1 amplitudes, most with risperidone and least with
      carbamazepine. Anterior delta and beta 2 amplitudes and interhemispheric
      coherence were increased directly proportional to plasma lithium levels.
      Nonresponders to treatment were identified at baseline by increased generalized
      theta amplitudes. After treatment, the nonresponders had higher amplitudes in the
      left temporal areas. Numerous qEEG associations with individual ratings of manic
      symptoms were found, more at baseline than after treatment. In general levels of
      psychopathology were negatively correlated with qEEG amplitudes. The qEEG
      findings appear to implicate dominant temporal lobe dysfunctions in mania.

PMID- 9571293
TI  - A comprehensive questionnaire for subjects undergoing quantitative research EEGs.

PMID- 9571294
TI  - Topographic analysis of EEG photic driving in patients with schizophrenia
      following clozapine treatment.
AB  - Reduced EEG photic driving has been found to be diagnostically sensitive and
      specific for schizophrenia. Thirty-one patients with schizophrenia were tested in
      this study to identify the typical and atypical neuroleptic effects on the photic
      driving. Compared with the placebo, clozapine significantly enhanced the
      photically driven EEG in theta and low alpha frequency band, while haloperidol
      did not have the same effect. These changes with clozapine appeared to be
      symmetrical and located primarily in the frontal, central and mid-parietal areas
      but not in the lateral parietal, temporal and occipital regions. Results were
      consistent with previous findings and suggested that the atypical EEG profile of
      clozapine might be associated with 5-HT2 antagonistic property.

PMID- 9571295
TI  - Frontal lobe functions and dysfunctions.
AB  - Frontal lobe syndromes with personality change are well known for about 150 years
      but mysteries of their underlying anatomophysiological mechanisms have started to
      unfold in recent years. The frontal lobe accommodates an extension of the primary
      motor (precentral) cortex, the premotor region and the interhemispherically
      located supplementary motor region, both of them forming area 6 and its
      subdivisions. The anterior and inferior frontal structures (and also the eye
      field, area 8) belong to the prefrontal region. The prefrontal cortex is also
      involved in motor action: in its initiation, planning, designing and sequencing
      rather than its mere execution. This requires drive and initiative to move, their
      deficits resulting in moderate to extreme apathy. Forces of motivation are likely
      to be mediated via the fronto-orbital cortex (known as an extension of the
      temporo-limbic system) which also exerts inhibitory influences on prefrontal
      functioning, and disinhibitory frontal lobe syndromes (from tactlessness to
      aggression) are the result of frontobasal impairment. A special form of frontal
      motor cortex disconnection may occur in childhood: in the rare Rett syndrome and,
      with limitation to the prefrontal cortex, in the common Attention Deficit
      Hyperactivity Disorder (ADHD). The initiation of movement is based upon the
      constant influx of afferent-sensory messages from posterior cerebral regions and
      strong mesiodorsal thalamic connections, providing information for each following
      initiatory prefrontal motor impulse which depends on such information from the
      past moment. This "Working Memory" appears to be the keystone of mental and motor
      prefrontal function. Becoming unnecessary in the next moments, the afferent
      signals undergo immediate extinction due to inhibitory fronto-orbital impulses.
      It is assumed that the classical absence attack with generalized spike-waves of
      frontal onset causes a "suspension of the working memory" and thus permits
      immediate postictal recuperation of frontal functions. The gap between afferent
      and efferent signals in the working memory is likely to permit neurocognitive
      processes and, in Homo sapiens, a widened gap is thought to provide a basis for
      reflection and cogitation uniquely human properties.

PMID- 9571296
TI  - Mapping epileptic foci by the dipole tracing method in a brain tumor patient with
      olfactory seizures: comparison with intraoperative electrocorticograms.
AB  - We estimated the position of the epileptic foci in a case of brain tumor with
      olfactory seizures using the Dipole Tracing Method (DTM) and compared the results
      with electrocorticograms (ECoGs) recorded during surgical resection. The case was
      a 24-year-old male. Electroencephalograms (EEG) showed frequent focal spikes in
      the right temporal area. Magnetic resonance imaging revealed a tumor in the right
      hippocampus region. We analyzed the spikes using DTM with a CDT-1000 EEG
      analyzer. The locations of two independent foci were analyzed; one was thought to
      be in the right hippocampus and the other in the right superior temporal gyrus.
      When the ECoG was taken, the results were in very close correlation with those of
      DTM, demonstrating the accuracy of DTM in the estimation of the location of
      epileptic foci in epileptic seizures with brain lesions.

PMID- 9571297
TI  - Coherence analysis of EEG changes during olfactory stimulation.
AB  - In a pilot study, EEG changes during odor stimulation were evaluated by coherence
      analysis. Ten normal adults were studied. Simultaneous recordings of 16 EEG
      channels with and without odor stimulation were stored on magnetic tape for
      further processing. EEG signals were analyzed using a signal analyzer. Coherence
      spectra were calculated between all possible channel pairs on the scalp. The
      amount of data was reduced by extracting broad band coherence values for five
      frequency bands: delta (2-3.9 Hz), theta (4-7.9 Hz), alpha 1 (8-9.9 Hz), alpha 2
      (10-12.9 Hz), and beta 1 (13-17.9 Hz). Coherence values extracted from the
      control EEG recordings and those during odor stimulation were compared to
      evaluate the presence of any significant differences. The results demonstrated
      significant changes in the EEG coherence between the two control recordings
      (before and after) in the theta and beta 1 bands. These frequency bands were
      therefore excluded from the examination. During odorant stimulation with methyl
      cyclopentenolone, the coherence in the delta band decreased in the frontal
      region, while that in the alpha 1 and alpha 2 bands increased in the bilateral
      temporal region. During odorant stimulation with scatol, the coherence in the
      delta band decreased in the frontal region, while that in the alpha 1 and alpha 2
      bands increased in the frontal, temporal and occipital regions. It is suggested
      that EEG coherence mapping may provide the basis for the development of an
      objective test of olfactory function in humans.

PMID- 9571298
TI  - Nonlinear dynamical analysis of periodic lateralized epileptiform discharges.
AB  - Nonlinear time series analysis can be used to investigate the dynamics underlying
      the generation of EEG signal. In the present study we used this approach to study
      the pathophysiology of PLEDs. We calculated the correlation dimension D2 of an
      EEG with typical PLEDs, and compared the results with those obtained for
      surrogate data. These surrogate data have the same power spectrum and amplitude
      distribution as the original EEG data, but are otherwise random. By construction,
      such surrogate data can be described by a linear model. Our results showed that
      D2 estimations for PLEDs were low, on the order of one, and that the results for
      EEG and the surrogate data were clearly different, indicating that the EEG with
      PLEDs reflects nonlinear dynamics of the underlying neural networks.

PMID- 9571299
TI  - TRI-PLEDs: a case report.
AB  - This case report shows an example of TRI-PLEDs, periodic discharges occurring
      independently on 3 different areas. The phenomenon of the PLED is briefly
      discussed.

PMID- 9571300
TI  - Clinical pharmacokinetics in the 21st century. Does the evidence support
      definitive outcomes?
AB  - Clinical pharmacokinetics emerged as a clinical discipline in the late 1960s and
      early 1970s. Clinical pharmacokinetic monitoring (CPM) helped many pharmacists to
      enter the clinical arena, but the focus was more on the pharmacists and tools.
      With the widespread acceptance of pharmaceutical care and patient-focused
      pharmacy, we now must take a sobering look at how clinical pharmacokinetics fits
      into the pharmaceutical care process. The existing literature is laden with
      articles that evaluate the effect of CPM on surrogate end-points. Many
      pharmacists have also had personal experiences that attest to the usefulness of
      CPM. Decreased mortality, decreased length of treatment, decreased length of
      hospital stay, decreased morbidity, and decreased adverse effects from drug
      therapy have been examined in an effort to measure and evaluate the impact of CPM
      on patient outcomes. While many of these studies demonstrated significant
      positive outcomes, several showed that CPM did not have a significant impact on
      specific patient outcomes. A few studies even found a negative impact on specific
      patient outcomes. Ultimately, there is good evidence in only a few specific
      patient groups to support the benefit of CPM. Despite the limitations of data
      supporting the routine use of CPM in managing drug therapy in diverse
      populations, many pharmacists continue to expend considerable time and effort in
      this activity. We need to define those patients who are most likely to benefit
      from CPM and incorporate this into our provision of pharmaceutical care, while
      minimising the time and money spent on CPM that provides no value. In redefining
      the patients who will benefit from CPM, we need to critically re-evaluate
      clinical studies on the relationship between drug concentration and response.
      Similarly, we need to pay special attention to recent studies evaluating the
      impact of CPM on outcomes in specific subpopulations. In the absence of specific
      studies demonstrating the value of CPM in particular patients, we propose that a
      more comprehensive decision-making process be undertaken that culminates in the
      quintessential question: 'Will the results of the drug assay make a significant
      difference in the clinical decision-making process and provide more information
      than sound clinical judgement alone?' We also need to consider opportunities to
      expand the use of CPM for new drugs and where new evidence suggests benefit. Even
      when there is strong evidence that CPM is useful in managing therapy in
      particular patient groups, clinicians need to remember that the therapeutic range
      is no more than a confidence interval and, therefore, we need to 'treat the
      patient and not the level'. We need to incorporate the patient-specific and
      outcome-oriented principles of pharmaceutical care into our CPM, even as we
      utilise CPM as an essential tool in pharmaceutical care.

PMID- 9571302
TI  - Pharmacodynamics and pharmacokinetics of spiramycin and their clinical
      significance.
AB  - The absolute bioavailability of oral spiramycin is generally within the range of
      30 to 40%. After a 1 g oral dose, the maximum serum drug concentration was found
      to be within the range 0.4 to 1.4 mg/L. The tissue distribution of spiramycin is
      extensive. The volume of distribution is in excess of 300 L, and concentrations
      achieved in bone, muscle, respiratory tract and saliva exceed those found in
      serum. The intracellular penetration of spiramycin is also rapid and extensive,
      with the concentrations in alveolar macrophages 10 to 20 times greater than
      simultaneous serum concentrations. Spiramycin is less metabolised than some of
      the other macrolides. The renal excretion of spiramycin is low, with 4 to 20% of
      the dose being excreted by this route. High concentrations of spiramycin are
      achieved in bile, which is an important route of elimination. The serum
      elimination half-life of spiramycin is between 6.2 and 7.7 hours. Of significance
      to clinicians may be the finding that spiramycin is highly concentrated in the
      respiratory tract and other tissues and macrophages. The post-antibiotic effect
      of spiramycin is significant and this effect is more prolonged than that of
      erythromycin against Staphylococcus aureus. Spiramycin has also been shown to
      greatly reduce the capacity of strains of Gram-positive cocci to adhere to human
      buccal cells.

PMID- 9571305
TI  - Overall cancer incidence and mortality trends among elderly and adult Europeans.

PMID- 9571301
TI  - Metabolism of the newer antidepressants. An overview of the pharmacological and
      pharmacokinetic implications.
AB  - Several chemically unrelated agents has been developed and introduced in the past
      decade, to supplement the earlier antidepressants. These include inhibitors of
      the reuptake of serotonin [the selective serotonin reuptake inhibitors (SSRI)] or
      noradrenaline (reboxetine) or both (milnacipran and venlafaxine), as well as
      drugs with distinct neurochemical profiles such as mirtazapine, nefazodone,
      moclobemide and tianeptine. Like the earlier drugs, these newer antidepressants
      are almost totally biotransformed before excretion, except for milnacipran whose
      clearance appears to be due equally to both urinary excretion and metabolism.
      Sometimes--as in the case of moclobemide--up to 20 metabolites have been
      identified in body fluids. In some cases, however, only a few metabolites have
      been detected, and a substantial proportion of the dose remains unaccounted for
      (e.g. fluoxetine and fluvoxamine). Metabolism generally proceeds through
      sequential or parallel oxidative pathways. These may be affected to varying
      degrees by physiological and pathological factors and those mediated by
      cytochrome P450 (CYP) 2D6 and CYP2C19 through genetic polymorphism. Some are
      influenced by chirality (e.g. the dealkylation of citalopram and fluoxetine),
      although information on this aspect of disposition is still lacking for other
      drugs existing as racemates (e.g. mirtazapine and tianeptine) and milnacipran,
      which is probably a mixture of 4 stereoisomers. Others again are saturable within
      the therapeutic range of doses (e.g. some pathways of metabolism of fluoxetine,
      fluvoxamine, nefazodone, paroxetine and venlafaxine). This may explain the
      individual variability with all these drugs which, from the pharmacokinetic point
      of view, is the same as with tricyclic agents. Our knowledge of the isoenzymes
      involved in the various oxidation pathways and their relevance for potential drug
      interactions varies from a considerable amount for most of the SSRI and
      nefazodone, to minimal for reboxetine and tianeptine. This information is useful
      for predicting the pharmacokinetic interactions mediated through inhibition of
      specific isoenzymes. This would be better appreciated if the enzymatic mechanisms
      involved in the biotransformation of the metabolite(s), and their role in drug
      interactions, were also known. This information is still lacking for some drugs,
      although metabolites may exhibit in vitro inhibitory potencies of similar to
      (paroxetine and its M2 metabolite as inhibitors of CYP2D6) or even greater than
      that of the parent drug (norfluoxetine is more potent than fluoxetine as an
      inhibitor of CYP3A3/4, and in view of the longer half-life (t1/2) of the
      metabolite the potential for interactions may persist for weeks after
      discontinuation of the parent drug). While we do know something about the
      biological activity of the metabolites of some of these drugs, we know very
      little about others. With few exceptions this knowledge refers only to the major
      metabolite(s) and regards the main in vitro effects as exerted by the parent
      drug. However, in vitro potency and selectivity may not translate directly into
      in vivo, and either major or minor metabolites may have characteristic in vitro
      and in vivo properties. For example, unlike the parent drug some minor ring
      opened metabolites of moclobemide have monoamine oxidase-B inhibitory activity in
      the rat, and the nefazodone metabolite m-chlorophenyl-piperazine shows activity
      on 5-HT2C receptors in rats and humans. Data on the brain-to-blood partition of
      metabolites compared with their parent drug are available only in a few cases.
      They are still not known for the main metabolites of fluvoxamine, milnacipran,
      mirtazapine, moclobemide, nefazodone, paroxetine, reboxetine and venlafaxine,
      despite the fact that total blood concentrations do not always reflect the
      metabolite: parent drug ratio in brain. Thus, in most cases, we do not really
      know what part hepatic metabolism plays in the overall effect of the administered
      parent drug.

PMID- 9571303
TI  - Heat exposure and drugs. A review of the effects of hyperthermia on
      pharmacokinetics.
AB  - Acute heat loading is encountered in several everyday situations, during physical
      exercise or work in a hot climate are just 2 examples. Special forms of heat
      exposure include different types of steam baths and saunas. External heating
      induces changes in haemodynamics, body fluid volume and blood flow distribution,
      which in turn may affect the pharmacokinetics of a drug and the therapeutic
      response. Documentation of the effects of heat exposure on the pharmacokinetics
      of drugs in humans is very limited, but based on the documentation some general
      conclusions can be drawn. The effects of external heating on absorption and
      elimination of those orally administered drugs which have been studied (e.g.
      midazolam, ephedrine, propranolol and tetracycline), have been minor. Systemic
      absorption of transdermally and subcutaneously administered drugs [insulin,
      nitroglycerin (glyceryl trinitrate) and nicotine] is in most cases enhanced by
      external heating, leading to higher plasma drug concentrations. In general,
      pharmacokinetic interactions between heat exposure and drug therapy are rare and
      limited to special situations, in which local blood flow (for example, over the
      skin) is enhanced many-fold because of hyperthermia. When pharmacodynamics are
      concerned, in most cases the probability of interactions is low, but in the
      treatment of malignant tumours hyperthermia may potentiate cytotoxic effects of
      drugs without enhancement of myelosuppressive effects.

PMID- 9571304
TI  - Predicting effective drug concentrations for individual patients. Determinants of
      pharmacodynamic variability.
AB  - Variability in the relationship between pharmacological effect intensity and drug
      concentration (pharmacodynamics) is pronounced, usually exceeding pharmacokinetic
      variability. Whereas interindividual differences are large, intra-individual
      differences are much smaller, unless the individual experiences certain
      pathophysiological changes such as deterioration of renal function or progression
      of a chronic disease (for example, Parkinson's disease). Failure to appreciate
      the magnitude of interindividual variability in the pharmacodynamics of a drug
      can compromise fixed dose clinical trial outcomes, making the drug appear less
      effective or more toxic. In the face of pharmacodynamic variability it becomes
      important to identify useful predictors (covariates) of pharmacodynamic
      individuality to facilitate individually optimised pharmacotherapy. This requires
      clinical trial designs that incorporate extensive patient profiling, well beyond
      the usual short list of demographics (such as age, gender, race, bodyweight and
      smoking habits). In searching for predictors, it is helpful to appreciate the
      factors that may account for interindividual differences in the relationship
      between pharmacological effect intensity and drug concentration in plasma or
      other appropriate fluid. They include receptor density and affinity, the
      formation and elimination kinetics of endogenous ligands (such as the
      enkephalins), postreceptor transduction processes, homeostatic responses and the
      kinetic characteristics of transporters involved in drug transfer between fluids
      of distribution and the biophase. Correction of drug concentrations in plasma for
      protein binding, consideration of active and interactive metabolites,
      stereospecific assays and attention to drug distribution disequilibria are
      essential for successful identification of factors affecting pharmacodynamic
      variability. Pharmaceutical delivery systems (the 'hardware') must be combined
      with guidance for individualising drug dosage (the 'software' or user's manual)
      to provide for optimal and cost-effective pharmacotherapy.

PMID- 9571307
TI  - Global health care: the role of geriatrician, general practitioner and oncology
      nurse.

PMID- 9571306
TI  - Prevalence of co-morbidity in newly diagnosed patients with cancer: a population
      based study.

PMID- 9571308
TI  - Screening and chemoprevention.

PMID- 9571309
TI  - Operative risk assessment.

PMID- 9571310
TI  - Signs, symptoms, early detection, staging and follow-up.

PMID- 9571311
TI  - Therapeutic choice with regard to life expectancy and cost benefit analysis in
      cancer diagnosis and treatment.

PMID- 9571312
TI  - Active protection from chemotherapy toxicity.

PMID- 9571313
TI  - Radiotherapy in the elderly.

PMID- 9571314
TI  - Psychosocial issues.

PMID- 9571315
TI  - Lung cancer.

PMID- 9571316
TI  - Breast cancer.

PMID- 9571317
TI  - Colorectal cancer.

PMID- 9571318
TI  - Prostate cancer.

PMID- 9571319
TI  - Gynaecologic cancers.

PMID- 9571320
TI  - Bladder cancer.

PMID- 9571321
TI  - Head and neck cancer.

PMID- 9571322
TI  - Lymphomas.

PMID- 9571323
TI  - Acute myelogenous leukaemia.

PMID- 9571324
TI  - Multiple myeloma.

PMID- 9571325
TI  - Sleep as a window on the developing brain.

PMID- 9571326
TI  - How should we respond to the worldwide diabetes epidemic?

PMID- 9571327
TI  - Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin
      and gemfibrozil in patients with NIDDM. A multicenter comparison study.
AB  - OBJECTIVE: To compare the lipid-lowering efficacies of simvastatin and
      gemfibrozil in NIDDM patients with combined (mixed) hyperlipidemia (CHL) or
      isolated hypercholesterolemia (IHC). RESEARCH DESIGN AND METHODS: Patients with
      primary dyslipidemia and NIDDM were recruited for this double-blind, double-dummy
      comparison study from 10 Finnish centers. After a 4-week placebo run-in period,
      they were randomly assigned to simvastatin or gemfibrozil. The simvastatin group
      (n = 47) received 10 mg once nightly for 8 weeks, 20 mg for the next 8 weeks, and
      40 mg for the third 8-week period. The gemfibrozil group (n = 49) received 600 mg
      twice daily throughout the 24 weeks. The lipid-lowering efficacies of both drugs
      were compared in all patients as well as separately in patients with CHL and IHC.
      RESULTS: In all patients, simvastatin reduced LDL and total cholesterol and the
      LDL-to-HDL cholesterol ratio more effectively, whereas gemfibrozil was more
      effective in elevating HDL cholesterol and decreasing triglyceride levels. The
      drug effects differed according to lipid phenotype at baseline. Simvastatin
      decreased LDL cholesterol levels by 30-40% in both phenotypes. Gemfibrozil caused
      a 15% reduction in LDL cholesterol in IHC but no change in CHL patients.
      Simvastatin produced 15-30% reductions in triglyceride levels in CHL but no
      change in IHC patients. Gemfibrozil caused reductions in triglycerides in CHL
      (50% and more) and in IHC (40%) patients, with 12-18% increases in HDL
      cholesterol in these groups. CONCLUSIONS: Simvastatin is useful in both CHL and
      IHC patients, whereas gemfibrozil can be used in patients with high triglyceride
      and low or normal LDL cholesterol levels.

PMID- 9571328
TI  - Glomerular charge and size selectivity assessed by changes in salt intake in type
      2 diabetic patients.
AB  - OBJECTIVE: To evaluate glomerular charge selectivity in patients with type 2
      diabetes, we studied changes in fractional clearance of proteins with different
      sizes and charges when patients were placed on two diets with different salt
      contents. RESEARCH DESIGN AND METHODS: Nineteen patients with type 2 diabetes and
      normoalbuminuria (< 20 micrograms/min, n = 8), microalbuminuria (20-100
      micrograms/min, n = 7), or advanced albuminuria (> 100 micrograms/min, n = 4)
      were placed on a low-salt diet (85 mEq of sodium daily) or a high-salt diet (255
      mEq of sodium daily) for 1 week, and then on the other diet, in random order.
      Fractional clearances of albumin and immunoglobulin G (IgG) were calculated on
      the last 3 days of each diet. RESULTS: In patients with normoalbuminuria, the
      high-salt diet increased the fractional clearance of IgG, which is electrically
      neutral, but the fractional clearance of albumin, which is anionic, was
      unaltered, suggesting that the pore charge of the glomerular barrier was
      unaffected. However, in patients with microalbuminuria, the high-salt diet
      increased the fractional clearances of IgG and albumin equally, indicating some
      neutralization of the pore charge. Fractional clearance of IgG in these first two
      groups was similar when salt intake was low, so pore size was the same in these
      groups. In patients with advanced albuminuria, fractional clearance of IgG was
      higher than in the other groups, indicating that size selectivity had worsened.
      CONCLUSIONS: In type 2 diabetic patients, charge selectivity is lost before size
      selectivity as diabetic nephropathy progresses.

PMID- 9571329
TI  - Normalization of plasma lipid peroxides, monocyte adhesion, and tumor necrosis
      factor-alpha production in NIDDM patients after gliclazide treatment.
AB  - OBJECTIVE: To evaluate the effect of gliclazide administration to NIDDM patients
      on 1) monocyte adhesion to cultured endothelial cells, 2) plasma cytokine and
      lipid peroxide levels, and 3) monocyte cytokine production. RESEARCH DESIGN AND
      METHODS: Poorly controlled glyburide-treated diabetic patients (n = 8) and
      healthy control subjects (n = 8) were recruited. At the beginning of the study,
      glyburide was replaced by an equivalent hypoglycemic dose of gliclazide. Serum
      and monocytes were isolated from blood obtained from control and diabetic
      subjects before and after 3 months of treatment with gliclazide. RESULTS: Plasma
      lipid peroxide levels and monocyte adhesion to endothelial cells are enhanced in
      NIDDM patients, and gliclazide administration totally reverses these
      abnormalities. Before gliclazide treatment, serum levels of cytokines did not
      differ in the control and the diabetic groups, with the exception of an
      enhancement of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6
      in NIDDM subjects. Basal and lipopolysaccharide (LPS)-stimulated monocyte
      production of interleukin-1 beta, IL-6, and IL-8 did not differ between the two
      groups. Furthermore, basal monocyte production of TNF-alpha was similar in the
      control and the diabetic groups, whereas a marked increase in the LPS-stimulated
      monocyte production of TNF-alpha was observed in the NIDDM group. Gliclazide
      treatment lowered LPS-stimulated TNF-alpha production by diabetic monocytes to
      levels similar to those observed in control subjects. CONCLUSIONS: Gliclazide
      administration to NIDDM patients inhibits the increased adhesiveness of diabetic
      monocytes to endothelial cells and reduces the production of TNF-alpha by these
      cells. These results suggest that treatment of NIDDM subjects with gliclazide may
      be beneficial in the prevention of atherosclerosis associated with NIDDM.

PMID- 9571330
TI  - Fish oil and glycemic control in diabetes. A meta-analysis.
AB  - OBJECTIVE: Hypertriglyceridemia is associated with cardiovascular disease in
      diabetes. Fibrates effectively lower, but do not always normalize, serum
      triglyceride levels. Fish oil supplements may then be added to lower serum
      triglyceride levels. Doubt remains whether the net effect of fish oil intake on
      glycemic control is beneficial in diabetes. We therefore performed a meta
      analysis from published clinical trials. RESEARCH DESIGN AND METHODS: Data
      sources were Medline (Cologne, Germany), Excerpta Medica, Current Contents,
      review articles, and published reference lists. Publications of 26 trials were
      selected, and all trials included more than five diabetes (IDDM and NIDDM)
      patients and addressed the effects of fish oil (eicosapentaenoic acid [EPA] and
      docosahexaenoic acid [DHA]) on serum lipids and glucose tolerance. We (C.E.F.,
      M.J.F.M.J.) extracted data independently based on predetermined criteria. Studies
      were classified according to design. RESULTS: All studies combined showed a
      decrease in mean triglyceride concentrations in association with fish oil: -0.60
      mmol/l (95% CI, -0.84 to -0.33, P < 0.01) and a slight but significant increase
      in serum LDL cholesterol: 0.18 mmol/l (95% CI, 0.04-0.32, P = 0.01), with both
      findings most prominent in NIDDM. No significant changes in HbA1c percentages
      occurred in diabetic subjects treated with fish oil. Fasting blood glucose levels
      were increased with borderline significance in NIDDM subjects (0.43 mmol/l [95%
      CI, 0.00-0.87], P = 0.06) and were significantly lower in IDDM subjects (-1.86
      mmol/l [95% CI, -3.1 to -0.61], P < 0.05). Significant dose-response effects of
      EPA (g/day) on HbA1c and triglycerides and of DHA (g/day) on fasting blood
      glucose levels, HbA1c, and triglycerides were demonstrated only in NIDDM
      subjects. CONCLUSIONS: The use of fish oil has no adverse affects on HbA1c in
      diabetic subjects and lowers triglyceride levels effectively by almost 30%.
      However, this may be accompanied by a slight increase in LDL cholesterol
      concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

PMID- 9571332
TI  - The prevalence of cutaneous manifestations in IDDM patients and their association
      with diabetes risk factors and microvascular complications.
AB  - OBJECTIVE: The aim of our study was to evaluate the frequency of skin
      manifestations, including the diabetic hand syndrome, in young IDDM patients. In
      addition, we studied the relation of the cutaneous manifestations to diabetes
      duration, glycemic control, and microvascular complications. RESEARCH DESIGN AND
      METHODS: The frequency of skin manifestations, including the diabetic hand
      syndrome, were examined in 238 IDDM patients (disease duration > 5 years) and 122
      healthy control subjects in a cross-sectional study. In addition, we studied the
      relation of the cutaneous manifestations with diabetes duration, glycemic
      control, BMI, microvascular complications, and stratum corneum hydration using a
      stepwise logistic regression. RESULTS: Diabetic skin manifestations were detected
      in 168 of 238 (71%) IDDM patients and in 18 of 122 (14%) of the control subjects.
      Ichthyosiform skin changes of the shins, scleroderma-like skin changes, tinea
      pedis, and dry scaly palms were detected in 48 vs. 7%, 39 vs. 0%, 32 vs. 7%, and
      21 vs. 0.8% of the patients and control subjects, respectively. In the diabetic
      patients, a significant association was found between ichthyosis of the shins and
      scleroderma-like skin changes of the hand (P < 0.001) and between scleroderma
      like skin changes and the skin dryness of the palms (P < 0.0001). When diabetic
      risk factors were considered, diabetes duration was significantly associated with
      scleroderma-like skin changes and ichthyosis of the shins (P < 0.0001). The
      latter was also found to be related to diabetic retinopathy (P < 0.0001).
      Keratosis pilaris was present in 21% of the patients versus 9% in control
      subjects and was found to be exclusively associated with high BMI. CONCLUSIONS:
      Acquired ichthyosis is a common finding and the most prevalent skin manifestation
      in young IDDM patients. The development of several skin manifestations in insulin
      dependent patients seems to be related to duration of diabetes and to development
      of diabetic microvascular complications.

PMID- 9571331
TI  - Diabetes in urban African-Americans. VI. Utility of fasting or random glucose in
      identifying poor glycemic control.
AB  - OBJECTIVE: African-Americans have an increased prevalence of both diabetes and
      diabetes complications, creating an imperative for improved metabolic control.
      Because American Diabetes Association guidelines recommend that action be taken
      when HbA1c is > 8.0%, but access to rapid-turnaround HbA1c assays remains
      limited, we tested the utility of fasting and random plasma glucose cutoffs as
      indicators of HbA1c > 8.0%. RESEARCH DESIGN AND METHODS: Using receiver operating
      characteristics (ROC) analysis, we evaluated the sensitivity, specificity, and
      predictive value of fasting and random plasma glucose measurements in identifying
      an HbA1c > 8.0% (fasting n = 974, random n = 552). The population studied was
      predominantly African-American, middle-aged, and non-insulin-dependent. RESULTS:
      Fasting plasma glucose was a significant indicator of HbA1c > 8.0%, both in the
      whole group and in subgroups for diet, sulfonylureas, and insulin; the
      corresponding areas under the ROC curve were 0.87, 0.90, 0.87, and 0.84,
      respectively (all P < 0.0001). A fasting plasma glucose cutoff of > 9.2 mmol/l
      (165 mg/dl) provided a sensitivity of 80% and a specificity of 83% for the whole
      group and a 77% positive predictive value. Random plasma glucose was also a good
      indicator of HbA1c > 8.0%, both in the whole group and in subgroups for diet,
      sulfonylureas, and insulin; the corresponding areas under the ROC curve were
      0.85, 0.91, 0.85, and 0.77, respectively (all P < 0.0001). A cutoff > 9.8 mmol/l
      (177 mg/dl) provided a sensitivity of 78% and a specificity of 77% for the whole
      group and a 78% positive predictive value. Overall, a plasma glucose > 11.1
      mmol/l (200 mg/dl) identified an HbA1c > 8.0% with a predictive value of
      approximately 90% if done while fasting and a predictive value of approximately
      80-85% if random. The utility of both fasting and random plasma glucose cutoffs
      was subsequently confirmed in a prospective study of another 2,309 and 1,396
      patients, respectively. CONCLUSIONS: Although glucose levels cannot replace HbA1c
      determinations, measurement of fasting or random plasma glucose may be used
      during a clinic visit to identify poorly controlled type 2 patients with
      reasonable certainty and allow timely patient education and therapeutic
      intervention.

PMID- 9571333
TI  - Ethnic differences in the glycemic response to exogenous insulin treatment in the
      Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM).
AB  - OBJECTIVE: The Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus was
      conducted in NIDDM patients to determine if a significant difference in HbA1c
      could be achieved between groups receiving standard and intensive treatment. We
      observed differences in the response to exogenous insulin between African
      Americans and other intensively treated patients. Therefore, we assessed the
      variations of response and correlated factors that might explain such
      differences. RESEARCH DESIGN AND METHODS: One hundred fifty-three men aged 40-69
      years with NIDDM for < or = 15 years were randomized to either the standard
      therapy (n = 78) or the intensive therapy (n = 75) arm. Of the 75 patients in the
      intensive therapy group, 57 completed the study on insulin therapy alone. Of
      these, 18 were African-Americans and 39 were non-African-Americans. We conducted
      an analysis of the data collected to determine differences in baseline
      characteristics, glycemic response, insulin requirement, body weight, exercise,
      and basal C-peptide level, factors that may explain a difference in response to
      insulin therapy. RESULTS: Glycemic control improved in all patients with
      intensive insulin therapy. African-Americans achieved a greater improvement in
      HbA1c compared with non-African-Americans with a similar increment in insulin.
      This difference could not be explained by differences in body weight, activity,
      concomitant use of other medicines, or insulin-secretory capacity of the
      pancreas. CONCLUSIONS: We conclude that ethnic differences may exist in the
      response to insulin therapy. A knowledge of such differences may aid in achieving
      good glycemic control, especially since minorities have a greater prevalence of
      and burden from the microvascular complications of diabetes.

PMID- 9571334
TI  - Serum leptin levels in smokers with type 2 diabetes.
AB  - OBJECTIVE: To elucidate the molecular mechanism of smoking cessation and its
      relationship to body weight gain, the effects of smoking on the serum levels of
      leptin were studied in Japanese patients with type 2 diabetes. RESEARCH DESIGN
      AND METHODS: The serum levels of leptin after an overnight fast in 37 adult male
      Japanese patients with type 2 diabetes (17 smokers and 20 nonsmokers) were
      assayed using radioimmunoassay. In addition, the serum leptin levels in four
      nondiabetic smokers were measured before and 2 weeks after quitting smoking.
      RESULTS: Smokers and nonsmokers did not differ in age, BMI, or levels of blood
      glucose and fasting insulin but did differ in HDL cholesterol levels (1.07 +/-
      0.18 vs. 1.32 +/- 0.24 mmol/l for smokers and nonsmokers, respectively, P =
      0.002). The mean serum leptin level of smokers did not differ from that of
      nonsmokers (3.8 +/- 1.9 vs. 3.8 +/- 1.6 ng/ml). The leptin level correlated with
      the fasting insulin level and BMI (r = 0.55 and 0.56, P < 0.001 and 0.001,
      respectively). The leptin levels in four heavy smokers showed no change after the
      subjects quit smoking (3.3 +/- 1.0 vs. 3.8 +/- 1.8 ng/ml, before and after
      quitting, respectively). CONCLUSIONS: Because smoking did not affect the leptin
      levels, the effects of quitting smoking on the fuel metabolism appear to be due
      to some other factors.

PMID- 9571335
TI  - Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance
      in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988
      1994.
AB  - OBJECTIVE: To evaluate the prevalence and time trends for diagnosed and
      undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in
      U.S. adults by age, sex, and race or ethnic group, based on data from the Third
      National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) and
      prior Health and Nutrition Examination Surveys (HANESs). RESEARCH DESIGN AND
      METHODS: NHANES III contained a probability sample of 18,825 U.S. adults > or =
      20 years of age who were interviewed to ascertain a medical history of diagnosed
      diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were
      obtained, and a subsample of 2,844 adults between 40 and 74 years of age who
      received an oral glucose tolerance test. The Second National Health and Nutrition
      Examination Survey, 1976-1980, and Hispanic HANES used similar procedures to
      ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes
      Association fasting plasma glucose criteria and the 1980-1985 World Health
      Organization (WHO) oral glucose tolerance test criteria. RESULTS: Prevalence of
      diagnosed diabetes in 1988-1994 was estimated to be 5.1% for U.S. adults > or =
      20 years of age (10.2 million people when extrapolated to the 1997 U.S.
      population). Using American Diabetes Association criteria, the prevalence of
      undiagnosed diabetes (fasting plasma glucose > or = 126 mg/dl) was 2.7% (5.4
      million), and the prevalence of impaired fasting glucose (110 to < 126 mg/dl) was
      6.9% (13.4 million). There were similar rates of diabetes for men and women, but
      the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times
      the rate for non-Hispanic whites. Based on American Diabetes Association
      criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total
      population of people who were 40-74 years of age increased from 8.9% in the
      period 1976-1980 to 12.3% by 1988-1994. A similar increase was found when WHO
      criteria were applied (11.4 and 14.3%). CONCLUSIONS: The high rates of abnormal
      fasting and postchallenge glucose found in NHANES III, together with the
      increasing frequency of obesity and sedentary lifestyles in the population, make
      it likely that diabetes will continue to be a major health problem in the U.S.

PMID- 9571337
TI  - Incidence and determinants of microalbuminuria in Koreans with type 2 diabetes.
AB  - OBJECTIVE: The incidence of diabetic nephropathy in type 2 diabetes differs
      widely by race. Although clinical proteinuria is reportedly more common in East
      Asian type 2 diabetic patients than in their Caucasian counterparts, data on the
      incidence of microalbuminuria are not available. This study was undertaken to
      investigate the incidence and the determinants of microalbuminuria in Korean type
      2 diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 188 Korean type 2
      diabetic patients with initial normoalbuminuria were followed prospectively for
      5.5 +/- 0.9 years in an outpatient clinic of a university hospital. The incidence
      of elevated urinary albumin excretion (UAE) (> 20 micrograms/min) and its
      relationship with baseline characteristics and follow-up data were determined.
      RESULTS: Of the 146 patients who finished the study, 37 showed persistently
      elevated UAE during follow-up, giving an incidence of 52/1,000 person-years. Age,
      duration of diabetes, and baseline UAE were significantly higher in the
      progressors than in the nonprogressors. More patients in the progressor group had
      retinopathy at baseline and at the end of follow-up. The mean values of fasting
      plasma glucose, HbA1, and systolic and diastolic blood pressure during the follow
      up period were significantly higher in the progressors than in the
      nonprogressors. Cox proportional hazards analysis revealed that presence of
      retinopathy, duration of diabetes, mean fasting plasma glucose, and mean systolic
      blood pressure during follow-up are independent variables that have a
      statistically significant influence on the development of microalbuminuria.
      CONCLUSIONS: The incidence of microalbuminuria in Korean type 2 diabetic patients
      is lower than that reported in Pima Indians with type 2 diabetes but is as high
      as that in Caucasians with type 1 diabetes. Presence of diabetic retinopathy,
      poor glycemic control, and high blood pressure are risk factors for development
      of microalbuminuria in Koreans with type 2 diabetes.

PMID- 9571336
TI  - Childhood diabetes in China. Enormous variation by place and ethnic group.
AB  - OBJECTIVE: To investigate the incidence rate of IDDM in China. RESEARCH DESIGN
      AND METHODS: The Chinese IDDM registry was established in 1991 as part of the
      World Health Organization's Multinational Project for Childhood Diabetes
      (DiaMond) project. Twenty-two centers were developed to monitor the incidence of
      IDDM in children < 15 years of age. The population under investigation includes >
      20 million individuals, representing approximately 7% of the children in China.
      Capture-recapture methods were used to estimate the ascertainment. RESULTS: The
      overall ascertainment-corrected IDDM incidence rate in China was 0.51 per
      100,000, the lowest rate ever reported. There was a 12-fold geographic variation
      (0.13-1.61 per 100,000). In general, the incidence rate was higher in the north
      and the east. There was a sixfold difference among ethnic groups (highest: Mongol
      group, 1.82 per 100,000; lowest: Zhuang group, 0.32 per 100,000). CONCLUSIONS:
      China has an extremely low overall IDDM incidence rate. China also has the
      greatest geographic and ethnic variation seen for any country.

PMID- 9571338
TI  - The effect of glycemic control in the pre-conception period and early pregnancy
      on birth weight in women with IDDM.
AB  - OBJECTIVE: To examine data from pregnancies in women with IDDM to assess the
      relative effects of mean glycosylated hemoglobin levels before conception, at
      booking, and during the 3 trimesters of pregnancy on birth weight. Good glycemic
      control during pregnancy in women with IDDM is important to minimize the risk of
      fetal malformation and macrosomia. Recent studies have suggested that glycemic
      control in the 1st trimester is more important than glycemic control during the
      2nd or 3rd trimesters. RESEARCH DESIGN AND METHODS: The case records of 65
      deliveries to women with IDDM were reviewed. Fifty-seven deliveries were included
      in the present study. Of the deliveries reviewed, 32 women were in their first
      pregnancy and 25 women were multiparous. Only viable pregnancies were included
      because the major outcome variable of interest was birth weight. Glycosylated
      hemoglobin was recorded for each time period. RESULTS: The median standardized
      birth weight was 1.1 SD higher than the nondiabetic mean. When pregnancies, in
      which the birth weight was greater than 1 SD above the nondiabetic mean, were
      compared with pregnancies, in which birth weight was less than 1 SD above the
      mean, significant differences were observed between the groups in HbA1 at 6-12
      months pre-conception (10.0 +/- 2.3 vs. 8.6 +/- 1.4%, P = 0.02), at 0-6 months
      pre-conception (10.2 +/- 2.4 vs. 8.7 +/- 2.0%, P = 0.03), at booking (9.5 +/- 2.2
      vs. 8.4 +/- 1.6%, P = 0.04), and at 0-12 weeks' gestation (9.5 +/- 2.2 vs. 8.0 +/
      1.3%, P = 0.04), but HbA1 later in pregnancy did not differ significantly
      between the groups. Correlational analysis of all 57 pregnancies revealed
      significant correlations between birth weight and HbA1 at 0-6 months pre
      conception (r = 0.44, P = 0.002), at booking (r = 0.43, P = 0.001), at 0-12
      weeks' gestation (r = 0.48, P = 0.001), at 12-24 weeks' gestation (r = 0.45, P =
      0.001), and at 24 weeks to term (r = 0.34, P = 0.009). However, with stepwise
      regression analysis, only HbA1 at 0-12 weeks' gestation entered into the equation
      with a multiple r value of 0.48. CONCLUSIONS: Glycemic control in the immediate
      pre-conception period and early 1st trimester appears to have a greater influence
      on birth weight than does glycemic control during the later weeks of pregnancy.

PMID- 9571340
TI  - The prevalence of diabetes in a Swedish population of 280,411 inhabitants. A
      report from the Skaraborg Diabetes Registry.
AB  - OBJECTIVE: To estimate the prevalence of known diabetes in a Swedish county
      (Skaraborg) and to evaluate capture-recapture methods for validation of the
      diabetes prevalence. RESEARCH DESIGN AND METHODS: Four sources were used to find
      known diabetic patients: 1) the Skaraborg Diabetes Registry (SDR), a case-finding
      inventory, 2) an administrative hospital registry, 3) a registry for the
      retinopathy screening program, and 4) a pharmacy prescription inventory. The
      capture-recapture method was applied to various combinations of sources to
      determine the prevalence of diabetes. RESULTS: The completeness of the SDR was
      88.4 +/- 1.3%, indicating a diabetes prevalence of 3.20 +/- 0.08%. When the SDR
      was not used as one of the sources, the estimated prevalence varied between 2.2
      and 4.5%. CONCLUSIONS: A case-finding registry is important in reliably
      estimating the prevalence of diabetes.

PMID- 9571339
TI  - Diabetes and long-term risk of mortality from coronary and other causes in middle
      aged Swedish men. A general population study.
AB  - OBJECTIVE: To assess the relation between cardiovascular risk factors and long
      term cause-specific mortality risk in middle-aged diabetic men, compared with men
      without diabetes. RESEARCH DESIGN AND METHODS: This prospective study analyzes a
      large random population sample of men over a follow-up of 16 years. At baseline
      in 1974-1977, 249 men with diabetes and 6,851 men without diabetes, all aged 51
      59 years, were identified. There were 2,126 deaths, 724 of which were due to
      coronary heart disease (CHD) and 1,001 deaths were due to any cardiovascular
      disease (CVD) cause. RESULTS: After adjustment for age, serum cholesterol,
      systolic blood pressure, smoking, BMI, and coronary disease at baseline, the
      relative risk of dying from any cause was 2.50 (95% CI, 2.11-2.95) in men with
      diabetes, compared with nondiabetic men, and 2.87 (2.31-3.57) for cardiovascular
      death. Men with diabetes had no significant excessive risk of dying from cancer
      or violent causes, but the relative risk of dying from any other
      noncardiovascular cause was 3.69 (2.55-5.34). Most of these deaths were due to
      diabetes and its complications. Hypercholesterolemia, smoking, and elevated
      systolic blood pressure predicted both coronary and all-cause mortality in
      diabetic as well as in nondiabetic men. Men with diabetes and serum cholesterol >
      7.2 mmol/l had a risk of dying from coronary disease of 45.3 and from any cause
      of 76.1 per 1,000 observation-years. In men with diabetes, the relative risk of
      dying associated with serum cholesterol > 7.2 mmol/l, as compared with < 5.2
      mmol/l, was 1.78 (95% CI, 1.05-3.02). The corresponding risk for nondiabetic men
      was 1.23 (1.04-1.46), and there was a statistically significant interaction
      between serum cholesterol and diabetes (P = 0.004). CONCLUSIONS: In men with
      diabetes, hypercholesterolemia, smoking, and hypertension predict coronary
      mortality risk, as well as mortality risk from all causes. Men with both diabetes
      and hypercholesterolemia have severely compromised survival and should be
      targeted for intervention aimed at lowering their lipid levels.

PMID- 9571341
TI  - Prevalence of glucose intolerance among Native Hawaiians in two rural
      communities. Native Hawaiian Health Research (NHHR) Project.
AB  - OBJECTIVE: To estimate prevalence of type 2 diabetes and impaired glucose
      tolerance (IGT) among a population of native Hawaiians in two rural communities.
      RESEARCH DESIGN AND METHODS: Prevalence of glucose intolerance was assessed in
      two rural communities by history (confirmed by record review) or with a 75-g oral
      glucose tolerance test according to World Health Organization criteria.
      Anthropometric and demographic data were also obtained. A short survey was used
      to estimate the prevalence of known diabetes among nonparticipants. Prevalence
      rates were adjusted using the standard world population of Segi. RESULTS: A total
      of 574 native Hawaiians age > or = 30 years participated. The crude prevalence of
      IGT and type 2 diabetes were 15.5 and 20.4%, respectively. Only IGT prevalence
      was significantly higher (P = 0.03) among women (18.7%) than among men (10.9%).
      Prevalence of glucose intolerance was significantly associated with BMI, waist
      circumference, and waist-to-hip ratio (WHR). After adjusting for age and BMI,
      waist circumference and WHR were significantly and independently associated with
      type 2 diabetes prevalence only among women. Prevalence of type 2 diabetes was
      not significantly associated with the percentage of Hawaiian ancestry after
      adjusting for age. CONCLUSIONS: This study observed a high prevalence of glucose
      intolerance associated with being overweight among native Hawaiians. Age-adjusted
      type 2 diabetes prevalence was four times higher than among the U.S. National
      Health and Nutrition Examination Survey (NHANES) II population. Prevalence was
      high despite high rates of admixture with other ethnic groups of Hawaii,
      suggesting that these other Asian and Pacific Island populations share similar
      susceptibility to type 2 diabetes risk.

PMID- 9571342
TI  - Physical activity and NIDDM in African-Americans. The Pitt County Study.
AB  - OBJECTIVE: Studies directly examining the association between physical activity
      and NIDDM in African-Americans are rare. Consequently, the strength of this
      association in this ethnic minority group remains unclear. The current study
      broadly characterizes the types of physical activity engaged in by a community
      sample of working-class African-Americans and then quantifies the association
      between physical activity and NIDDM risk in this population. RESEARCH DESIGN AND
      METHODS: During the 1993 reexamination of participants in the Pitt County Study
      in North Carolina, data on NIDDM history, current use of insulin or oral
      hypoglycemic drugs, and approximately 12-h overnight fasting blood glucose (FBG)
      were obtained from 598 women and 318 men, ages 30-55 years. The presence of NIDDM
      was determined by current insulin or medication use and FBG > or = 140 mg/dl.
      Study participants were assigned to one of four categories of physical activity:
      strenuous, moderate, low, or inactive. RESULTS: The weighted prevalence of NIDDM
      in the sample was 7.1%. After adjustment was made for age, sex, education, BMI,
      and waist-to-hip ratio, NIDDM risk for moderately active subjects was one-third
      that for the physically inactive subjects (odds ratio [OR], 0.35; 95% CI, 0.12
      0.98). The ORs for low (OR, 0.51; 95% CI, 0.20-1.29) and strenuous (OR, 0.65; 95%
      CI, 0.26-1.63) activity also tended to be lower. A summary OR that contrasted any
      activity versus no activity was 0.51 (95% CI, 0.23-1.13). CONCLUSIONS: Moderate
      physical activity was strongly associated with reduced risk for NIDDM in this
      sample. While replication of these findings is needed, public health
      interventions designed to increase moderate (leisure-time) physical activity in
      black adults should be strongly encouraged.

PMID- 9571343
TI  - Diabetes and impaired glucose tolerance in three Alaskan Eskimo populations. The
      Alaska-Siberia Project.
AB  - OBJECTIVE: The objectives of this study were to determine the prevalence of
      diabetes and impaired glucose tolerance (IGT) in three Alaskan Eskimo
      populations, using standardized diagnostic criteria, and to evaluate family
      history and obesity as risk factors. RESEARCH DESIGN AND METHODS: This cross
      sectional study involved men and women > or = 25 years of age from three Eskimo
      ethnic groups (Siberian Yupik, Central Yupik, and Inupiat) residing in
      northwestern Alaska. Glucose tolerance status was defined by World Health
      Organization criteria and was based on a 75-g oral glucose tolerance test. Data
      on age, family history of diabetes, and degree of Eskimo ancestry were obtained
      from a personal interview. Obesity was assessed using BMI. RESULTS: A total of
      454 of 899 (50.5%) eligible participants were examined for diabetic status (239
      Siberian Yupik, 106 Central Yupik, and 109 Inupiat participants). The prevalence
      of diabetes was more than twice as high among the Siberian Yupik (9.6%) as among
      the Central Yupik (2.8%) and Inupiat participants (3.7%). Diabetes was more
      prevalent in women than men (8.8 vs. 4.2%). IGT was found in an additional 11.7%
      of the women and 4.7% of the men. The combined prevalence of diabetes and IGT in
      the population > or = 55 years of age was 30.4% (diabetes 12.0%, IGT 18.4%). Of
      the people identified with diabetes, 47% had not been previously diagnosed. Age
      specific prevalences were similar to those found in U.S. whites in the National
      Health and Nutrition Examination Survey II. After adjustment for age, family
      history of diabetes was associated with diabetes in study participants with an
      odds ratio of 4.4, while obesity was associated with diabetes with an odds ratio
      of 2.6. CONCLUSIONS: These prevalences of diabetes are the highest yet reported
      among Eskimo populations. Obesity and family history of diabetes are associated
      with increased odds of developing diabetes. These data underscore the need to
      further examine risk factors and to design effective interventions.

PMID- 9571344
TI  - Postprandial insulin lispro. A new therapeutic option for type 1 diabetic
      patients.
AB  - OBJECTIVE: For intensified insulin therapy of type 1 diabetes, bolus injection of
      regular human insulin 30-15 min before a meal is currently recommended. This
      randomized study is aimed to determine whether insulin lispro (LIS), a new
      insulin analog with a rapid onset of action, can provide comparable blood glucose
      (BG) control by injection after the meal. RESEARCH DESIGN AND METHODS: Eighteen
      type 1 diabetic subjects injected regular insulin (REG) at 40, 20, or 0 min
      before or LIS at 20 or 0 min before or 15 min after the start of a standardized
      test meal. BG excursions and area under the curve of BG excursions (AUC) at the
      six visits were compared by analysis of variance. Hypoglycemic events (BG < or =
      2.78 mmol/l) were evaluated in relation to the achieved postprandial BG control.
      RESULTS: Mean AUC values were 2.00, 2.55, and 3.33 mmol.h.l-1 for REG given 40,
      20, and 0 min before the test meal, respectively, and -2.19, -2.15, and 1.98
      mmol.h.l-1 for LIS given 20 and 0 min before and 15 min after the start of the
      test meal, respectively. LIS injected 20 min (-20) or immediately (0) before the
      meal was significantly more effective in controlling postprandial BG excursion (P
      < 0.001) than any REG treatment. Postprandial injection of LIS (15) did not
      compromise postprandial BG control and resulted in less hypoglycemia. REG -40 and
      LIS -20 were associated with early hypoglycemia, but other hypoglycemic events
      were equally distributed among groups. CONCLUSIONS: The optimal time for bolus
      insulin injection was 20 min before the meal for REG and immediately before the
      meal for LIS. LIS injected immediately after a standard meal provided
      postprandial BG control at least as good as REG injected from 40 to 0 min before
      the meal. Postprandial injection of LIS is an attractive new therapeutic option.

PMID- 9571345
TI  - Response to intensive therapy steps and to glipizide dose in combination with
      insulin in type 2 diabetes. VA feasibility study on glycemic control and
      complications (VA CSDM).
AB  - OBJECTIVE: The feasibility study for the VA Cooperative Study on Glycemic Control
      and Complications in Type 2 Diabetes (VA CSDM) prospectively studied 153 insulin
      requiring type 2 diabetes patients, randomized between an intensively treated arm
      and a standard treatment arm during a mean follow-up of 27 months. The glycemic
      response to each of the progressive, sequential phases of insulin treatment was
      assessed, along with the incidence of hypoglycemic reactions and the relative
      efficacy of different doses of glipizide in combination with fixed doses of
      insulin. RESEARCH DESIGN AND METHODS: Five medical centers participated; half of
      the patients were assigned to the intensive treatment arm aiming for normal HbA1c
      levels. Age of patients was 60 +/- 6 years, duration of diabetes 8 +/- 3 years,
      and BMI 30.7 +/- 4 kg/m2. A four-step management technique was used, with
      patients moving to the next step if the operational goals were not met: Phase I,
      evening intermediate or long-acting insulin; phase II, added day-time glipizide;
      phase III, two injections of insulin alone; and phase IV, multiple daily insulin
      injections. Home glucose monitoring measurements were done twice daily and at
      3:00 A.M. once a week. Hypoglycemic reactions and home glucose monitoring results
      were recorded and counted in each of the treatment phases. RESULTS: Baseline
      HbA1c was 9.3 +/- 1.8%, and fasting plus serum glucose was 11.4 +/- 3.3 mmol/1.
      Fasting serum glucose fell to near normal in phase I, and remained so in the
      other treatment phases. An HbA1c separation of 2.1% between the arms was
      maintained during the course of the study, while the intensive arm kept HbA1c
      levels below 7.3% (P = 0.001). Most of the decrease in HbA1c occurred with one
      injection of insulin alone (phase I, -1.4%) or adding day-time glipizide (phase
      II, -1.9% compared with baseline). HbA1c did not decrease further after
      substituting two injections of insulin alone, with twice the insulin dose.
      Multiple daily injections resulted in an additional HbA1c fall (-2.4% compared
      with baseline). However, two-thirds of the patients were still on one or two
      injections a day at the end of the study. Changes in home glucose monitoring
      levels paralleled those of the HbA1c, as did the increments in number of reported
      hypoglycemic reactions, virtually all either "mild" or "moderate" in character.
      For the combination of glipizide and insulin (phase II), the only significant
      effect was obtained with daily doses up to 10 mg a day; there were no significant
      additional benefits with up to fourfold higher daily doses, and HbA1c levels had
      an upward trend with doses > 20 mg/day. CONCLUSIONS: A simple regime of a single
      injection of insulin, alone or with glipizide, seemed sufficient to obtain
      clinically acceptable levels of HbA1c for most obese, insulin-requiring type 2
      diabetes patients. Further decrease of HbA1c demanded multiple daily injections
      at the expense of doubling the insulin dose and the rate of hypoglycemic events.
      In combination therapy, doses of glipizide > 20 mg/day offered no additional
      benefit.

PMID- 9571346
TI  - Low-intensity laser irradiation improves skin circulation in patients with
      diabetic microangiopathy.
AB  - OBJECTIVE: Diabetic foot problems due to angiopathy and neuropathy account for
      50% of all nontraumatic amputations and constitute a significant economic burden
      to society. Low-intensity laser irradiation has been shown to induce wound
      healing in conditions of reduced microcirculation. We investigated the influence
      of low-intensity laser irradiation by means of infrared thermography on skin
      blood circulation in diabetic patients with diabetic microangiopathy. RESEARCH
      DESIGN AND METHODS: Thirty consecutive patients with diabetic ulcers or gangrenes
      and elevated levels of glycosylated hemoglobin were randomized by blocks of two
      to receive either a single low-intensity laser irradiation with an energy density
      of 30 J/cm2 or a sham irradiation over both forefoot regions in a double-blind
      placebo-controlled clinical study. Skin blood circulation as indicated by
      temperature recordings over the forefoot region was detected by infrared
      thermography. RESULTS: After a single transcutaneous low-intensity laser
      irradiation, a statistically significant rise in skin temperature was noted (P <
      0.001 by ANOVA for repeated measurements), whereas in the sham-irradiated control
      group, a slight but significant drop in temperature (P < 0.001) was found.
      Subsequently performed contrasts for comparison of measurements before and after
      irradiation revealed significant temperature increases at 20 min of irradiation
      time (P < 0.001), at the end of the irradiation (P < 0.001), and 15 min after
      stopping the irradiation (P < 0.001). In the sham-irradiated feet, the drop in
      local skin temperature was not significant at 20 min (P = 0.1), but reached
      significance at the end of the sham-irradiation procedure (P < 0.001) and 15 min
      after the end of sham irradiation (P < 0.001). CONCLUSIONS: The data from this
      first randomized double-blind placebo-controlled clinical trial demonstrate an
      increase in skin microcirculation due to athermic laser irradiation in patients
      with diabetic microangiopathy.

PMID- 9571347
TI  - Validation of home blood glucose meters with respect to clinical and analytical
      approaches.
AB  - OBJECTIVE: To evaluate the clinical and analytical accuracy of home blood glucose
      meters. RESEARCH DESIGN AND METHODS: Six blood glucose meters--Reflolux S
      (Boehringer Mannheim, Mannheim, Germany), One Touch II (LifeScan, Milpitas, CA),
      Glucocard Memory (Menarini, Florence, Italy), Precision QID (Medisense,
      Cambridge, U.K.), HaemoCue (HaemoCue, Angelholm, Sweden), and Accutrend alpha
      (Boehringer Mannheim, Mannheim, Germany)--were compared with a reference method
      (Beckman Glucose Analyzer II) under controlled conditions (glucose clamp
      technique). Validation of the blood glucose meters was accomplished by clinically
      oriented approaches (error grid analysis), statistical approaches (variance
      components analysis), and by the criteria of the American Diabetes Association
      (ADA), which recommend a target variability of < 5%. RESULTS: A total of 1,794
      blood glucose monitor readings and 299 reference values ranging from 2.2 to 18.2
      mmol/l were analyzed (705 readings < 3.89 mmol/l, 839 readings between 3.89 and
      9.99 mmol/l, and 250 readings > 9.99 mmol/l). According to error grid analysis,
      only Reflolux S and Glucocard M had 100% of estimations within the clinically
      acceptable zones A and B. Assessment of analytical accuracy revealed substantial
      differences between the glucose meters after separation of the data into defined
      glycemic ranges. None of the devices met the ADA criteria. CONCLUSIONS: To
      evaluate accuracy of blood glucose meters, error grid analysis, as well as
      statistical models, are helpful means and should be performed together.
      Analytical performance of currently available home blood glucose meters differs
      substantially within defined glycemic ranges.

PMID- 9571348
TI  - An electronic case manager for diabetes control.
AB  - OBJECTIVE: To evaluate the usage and safety of an electronic case manager (ECM)
      system designed to facilitate the task of glycemic control. Sustained improvement
      in blood glucose control is the proven treatment outcome that will reduce or
      eliminate the long-term complications of diabetes. RESEARCH DESIGN AND METHODS: A
      customized microcomputer system served as the ECM. Located at the clinic, this
      voice-interactive system required the remote patient to need only a touch-tone
      telephone. Patients accessed the system to report daily self-measured glucose
      levels or hypoglycemic symptoms together with associated lifestyle events. System
      beta-testing was in an open-case series (n = 184) in an academic diabetes center
      with the goal of evaluating the ECM in terms of utilization, frequency of crises,
      and fiscal matters. RESULTS: Of the patients, 58% (n = 107) actively used the ECM
      for their daily diabetes care, accumulating 788 patient-months of follow-up. Over
      45,000 telephone calls were received by the ECM during the start-up year. Each
      call was processed instantly and automatically. Patients benefited from having 24
      h access to the ECM. Prevalence of diabetes-related crises (hyperglycemia > 400
      mg/dl [22 mmol/l] or hypoglycemia < 50 mg/dl [2.8 mmol/l]) decreased
      approximately threefold (P < 0.05), with a concomitant statistically significant
      decrease in HbA1c of 0.8% at 6 months (n = 45, P = 0.024) and 0.9% at 12 months
      (n = 30, P = 0.044). The ECM provided 24-h on-line assistance in adjusting daily
      insulin and/or tablet therapy, automatic generation of standardized medical
      reports, electronic medical-legal documentation, as well as a marked reduction in
      the time spent on the phone with patients. Clinic visits in managing complex
      diabetes were reduced approximately twofold (P < 0.0001), and the effort spent by
      case managers was estimated. CONCLUSIONS: Patients with diabetes who accessed the
      ECM system received timely, cost-effective, and reliable medical intervention.
      This reduced the incidence of diabetic crises and the need for frequent clinic
      visits. The ECM empowers case managers to provide safer and superior diabetes
      care.

PMID- 9571350
TI  - Muscular endurance in long-term IDDM patients.
AB  - OBJECTIVE: To determine the short-term muscular endurance and working capacity of
      leg muscles in long-term IDDM patients in relation to neuropathic complications,
      muscle strength, and metabolic control. RESEARCH DESIGN AND METHODS: The muscular
      endurance of extensors and flexors at the ankle and knee was assessed in 44 IDDM
      patients and in 44 matched control subjects during 30 maximal isokinetic
      movements. The endurance index was the work performance of the last 5 movements
      relative to the first 5 movements. Total work was the summated work of all
      movements. All patients underwent a neurological evaluation, nerve conduction
      studies, and quantitative sensory tests. RESULTS: The combined endurance index of
      the ankle extensors and flexors was 70% (51-88) (median [range]) in the diabetic
      group and 65% (55-82) in the control group (P < 0.01). For knee extensors and
      flexors the combined endurance index was 65% (55-103) for the diabetic patients
      and 63% (48-75) in the control subjects (P < 0.01). The endurance index related
      neither to the severity of neuropathy nor to the metabolic control (blood glucose
      and HbA1c) for any of the muscle groups. Diabetic patients had reduced strength
      of all muscle groups (14-24%, P < 0.02) and impaired total work performance (15
      20%, P < 0.01) for ankle movements. CONCLUSIONS: Long-term IDDM patients have
      increased endurance but reduced strength and work performance of leg muscles. The
      combined effect of the motor abnormalities is suggested to give rise to
      functional impairment, including an increased risk of falls and injuries.

PMID- 9571349
TI  - Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events
      Randomized Trial (FACET) in patients with hypertension and NIDDM.
AB  - OBJECTIVE: ACE inhibitors and calcium antagonists may favorably affect serum
      lipids and glucose metabolism. The primary aim of the Fosinopril Versus
      Amlodipine Cardiovascular Events Randomized Trial (FACET) was to compare the
      effects of fosinopril and amlodipine on serum lipids and diabetes control in
      NIDDM patients with hypertension. Prospectively defined cardiovascular events
      were assessed as secondary outcomes. RESEARCH DESIGN AND METHODS: Inclusion
      criteria included a diagnosis of NIDDM and hypertension (systolic blood pressure
      of > 140 mmHg or diastolic blood pressure of > 90 mmHg). Exclusion criteria
      included a history of coronary heart disease or stroke, serum creatinine > 1.5
      mg/dl, albuminuria > 40 micrograms/min, and use of lipid-lowering drugs, aspirin,
      or antihypertensive agents other than beta-blockers or diuretics. A total of 380
      hypertensive diabetics were randomly assigned to open-label fosinopril (20
      mg/day) or amlodipine (10 mg/day) and followed for up to 3.5 years. If blood
      pressure was not controlled, the other study drug was added. RESULTS: Both
      treatments were effective in lowering blood pressure. At the end of follow-up,
      between the two groups there was no significant difference in total serum
      cholesterol, HDL cholesterol, HbA1c, fasting serum glucose, or plasma insulin.
      The patients receiving fosinopril had a significantly lower risk of the combined
      outcome of acute myocardial infarction, stroke, or hospitalized angina than those
      receiving amlodipine (14/189 vs. 27/191; hazards ratio = 0.49, 95% CI = 0.26
      0.95). CONCLUSIONS: Fosinopril and amlodipine had similar effects on biochemical
      measures, but the patients randomized to fosinopril had a significantly lower
      risk of major vascular events, compared with the patients randomized to
      amlodipine.

PMID- 9571351
TI  - The association between a family history of type 2 diabetes and coronary artery
      disease in a type 1 diabetes population.
AB  - OBJECTIVE: To examine whether a potential marker for type 2 diabetes (family
      history) is related to CAD in type 1 diabetic subjects. The two major types of
      primary diabetes, type 1 and type 2, are both associated with an increased risk
      of developing coronary artery disease (CAD). However, the etiology and associated
      risk factors may differ by type of diabetes. In type 2 diabetes, CAD is likely to
      be linked with the insulin resistance associated with the type 2 "process," while
      CAD in type 1 diabetes has, so far, been more closely linked to renal disease.
      Because the etiologies of type 1 and type 2 diabetes are different, it is
      possible that some CAD in type 1 diabetes may be related to the coexistence of
      type 2 diabetes susceptibility (i.e., insulin resistance). RESEARCH DESIGN AND
      METHODS: We evaluated the interrelationships between family history of type 2
      diabetes (age at onset > 30 years, no insulin for 1st year) and presence of CAD
      in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh
      Epidemiology of Diabetes Complications study (n = 658). RESULTS: A first-degree
      family history of type 2 diabetes was reported in 112 subjects, and CAD was
      present in 119 subjects. Those subjects reporting a family history of type 2
      diabetes were significantly older, had a longer duration of type 1 diabetes, had
      higher triglyceride and LDL cholesterol levels, and had a borderline
      significantly increased Beck depression inventory. Sex differences in CAD risk
      factors were also noted. Using logistic regression analysis, the odds ratio (95%
      CI) for the presence of CAD in association with a family history of NIDDM was
      1.89 (1.27-2.84). The odds ratio (95% CI) after adjusting for disease duration,
      triglycerides, hypertension, Beck depression, and nephropathy status was 1.45
      (0.87-2.28). CONCLUSIONS: We conclude that a family history of type 2 diabetes is
      a risk factor for CAD in type 1 diabetic subjects. This supports the concept that
      insulin resistance may contribute to development of CAD in type 1 diabetes.

PMID- 9571352
TI  - Ratio of motor nerve conduction velocity to F-wave conduction velocity in
      diabetic neuropathy.
AB  - OBJECTIVE: To investigate the usefulness of a new parameter, the ratio of motor
      nerve conduction velocity to F-wave conduction velocity (M/F ratio), for the
      differential diagnosis of diabetic neuropathy. RESEARCH DESIGN AND METHODS: Nerve
      conduction studies were conducted in 95 patients with diabetic neuropathy, 44
      nondiabetic patients with peripheral neuropathy, and 24 normal control subjects.
      Nondiabetic patients with neuropathy were grouped by clinical diagnosis as
      follows: segmental demyelination (n = 15), axonal neuropathy (n = 11), alcoholic
      polyneuropathy (n = 4), and other polyneuropathy (n = 14). Motor nerve conduction
      velocity (MCV) of post-tibial nerves, sensory nerve conduction velocity (SCV) of
      sural nerves, and F-wave conduction velocity (FWCV) of post-tibial nerves were
      measured by standardized techniques. The M/F ratio was calculated from these
      measurements. RESULTS: The MCV and SCV of diabetic patients were significantly
      slower and the M/F ratio was significantly lower than those of normal subjects:
      MCV, 43.7 +/- 5.4 vs. 47.1 +/- 2.9 m/s, P < 0.001; SCV, 44.7 +/- 11.1 vs. 48.3 +/
      5.7 m/s, P < 0.05; M/F ratio, 0.84 +/- 0.09 vs. 0.90 +/- 0.06, P < 0.001. The
      FWCV of nondiabetic patients with neuropathy was significantly slower (40.0 +/-
      6.3 vs. 48.3 +/- 4.0 m/s, P < 0.001) and the M/F ratio was significantly higher
      (1.04 +/- 0.12, P < 0.001) than that of normal subjects, respectively. Although
      MCV, SCV, and FWCV were correlated with age in normal control subjects, the M/F
      ratio was independent of age in the diabetic as well as the nondiabetic patients
      with neuropathy. CONCLUSIONS: Results suggest that the M/F ratio, which is
      influenced by the neuronal damages in the distal segment of peripheral nerves, is
      useful in the differential diagnosis of diabetic neuropathy.

PMID- 9571353
TI  - Relationship between serum 1,5-anhydroglucitol and urinary excretion of N
      acetylglucosaminidase and albumin determined at onset of NIDDM with 3-year follow
      up.
AB  - OBJECTIVE: This prospective study was designed to elucidate the relationship
      between the serum level of 1,5-anhydroglucitol (1,5AG) and the urinary excretion
      of N-acetylglucosaminidase (NAG) and albumin in patients who were in the early
      stages of diabetes. RESEARCH DESIGN AND METHODS: A total of 1,062 male
      nondiabetic subjects with impaired glucose tolerance were monitored for blood
      glucose level once every 2-3 months, and the values were evaluated. Of these
      1,062 subjects, 112 showed a worsening of glycemia during the observation period
      to the level seen in diabetes. We began to monitor the glycemia and parameters of
      renal damage in the 112 patients from the onset of diabetes. RESULTS: The urinary
      excretion of NAG and albumin were elevated even at the onset of diabetes. The
      abnormal excretion of NAG and albumin was associated with a change in serum 1,5AG
      and was quickly reversible when the serum 1,5AG improved. In the 3 years after
      the onset of diabetes, we obtained at least 18 measurements of one parameter for
      each patient and calculated the mean. Urinary NAG was found to be significantly
      correlated with the fasting plasma level of glucose (FPG; r = 0.512, P < 0.0001),
      the level of HbA1 (r = 0.351, P = 0.001), and the level of 1,5AG (r = -0.790, P <
      0.0001). The urinary excretion of albumin was weakly but significantly correlated
      with levels of FPG (r = 0.383, P < 0.0001) and HbA1 (r = 0.337, P < 0.0001), but
      it was more strongly correlated with 1,5AG (r = -0.632, P < 0.0001). The level of
      1,5AG was significantly correlated with FPG (r = -0.681, P < 0.0001) and HbA1 (r
      = -0.609, P < 0.0001). CONCLUSIONS: When the renal damage is not severe, the
      serum level of 1,5AG appeared to be an indicator of the reversible renal damage
      caused by hyperglycemia, as well as of the severity of the glycemia itself.

PMID- 9571354
TI  - Angiographic evaluation of peripheral arterial occlusive disease and its role as
      a prognostic determinant for major amputation in diabetic subjects with foot
      ulcers.
AB  - OBJECTIVE: To evaluate in diabetic patients with foot ulcers the angiographic
      findings of peripheral occlusive arterial disease and their role as a prognostic
      determinant for major amputation. RESEARCH DESIGN AND METHODS: From 1993 to 1995,
      104 diabetic inpatients with foot ulcers underwent arteriography on the ulcerated
      limb. Stenoses in the iliac trunk, the superficial femoral artery, the profunda
      femoral artery, the popliteal artery, the anterior tibial artery, the posterior
      tibial artery, and the peroneal artery were scored on the basis of vessel lumen
      reduction: 0 if stenoses involved a reduction in the vessel lumen of < 50%, 1 if
      stenoses involved 50 to < 75% reduction, 2 if stenoses involved 75 to < 100%
      reduction, and 3 if total occlusion was present. The sum of the points assigned
      to each of these arteries was called the angiographic score. RESULTS: Stenoses
      causing a vessel lumen reduction > or = 50% were detected in 103 patients (99%).
      Stenoses were also detected in subjects with palpable foot pulses, ankle-brachial
      indexes > or = 1, or transcutaneous oxygen tension > or = 50 mmHg. The risk of
      major amputation was increased significantly when total occlusion was present in
      the popliteal and infrapopliteal arteries (chi 2 for trend = 50.57, P < 0.001).
      No major amputation was carried out in patients with angiographic scores < 10;
      major amputation was carried out in all the patients with scores > 14.
      Multivariate analysis indicated a high angiographic score as an independent risk
      factor for major amputation (odds ratio 2.32, P = 0.001, CI 1.40-3.84).
      CONCLUSIONS: Angiography permits an exact detection of occlusive arterial disease
      in subjects with normal results for noninvasive vascular procedures. A score that
      has a relevant prognostic value for major amputation can be obtained from the
      evaluation of the extent and diffusion of the stenoses.

PMID- 9571356
TI  - Arrhythmias and mortality after myocardial infarction in diabetic patients.
      Relationship to diabetes treatment.
AB  - OBJECTIVE: To assess the relationship between clinical course after acute
      myocardial infarction (AMI) and diabetes treatment. RESEARCH DESIGN AND METHODS:
      Retrospective analysis of data from all patients aged 25-64 years admitted to
      hospitals in Perth, Australia, between 1985 and 1993 with AMI diagnosed according
      to the International Classification of Diseases (9th revision) criteria was
      conducted. Short- (28-day) and long-term survival and complications in diabetic
      and nondiabetic patients were compared. For diabetic patients, 28-day survival,
      dysrhythmias, heart block, and pulmonary edema were treated as outcomes, and
      factors related to each were assessed using multiple logistic regression.
      Diabetes treatment was added to the model to assess its significance. Long-term
      survival was compared by means of a Cox proportional hazards model. RESULTS: Of
      5,715 patients, 745 (12.9%) were diabetic. Mortality at 28 days was 12.0 and
      28.1% for nondiabetic and diabetic patients, respectively (P < 0.001); there were
      no significant drug effects in the diabetic group. Ventricular fibrillation in
      diabetic patients taking glibenclamide (11.8%) was similar to that of nondiabetic
      patients (11.0%) but was lower than that for those patients taking either
      gliclazide (18.0%; 0.1 > P > 0.05) or insulin (22.8%; P < 0.05). There were no
      other treatment-related differences in acute complications. Long-term survival in
      diabetic patients was reduced in those taking digitalis and/or diuretics but type
      of diabetes treatment at discharge had no significant association with outcome.
      CONCLUSIONS: These results do not suggest that ischemic heart disease should
      influence the choice of diabetes treatment regimen in general or of sulfonylurea
      drug in particular.

PMID- 9571355
TI  - Effects of perindopril and carvedilol on endothelium-dependent vascular functions
      in patients with diabetes and hypertension.
AB  - OBJECTIVE: To compare the effects of the ACE inhibitor perindopril and the beta
      blocker carvedilol on blood pressure and endothelial functions in NIDDM patients
      with hypertension. RESEARCH DESIGN AND METHODS: We conducted a double-blind
      randomized trial in 26 patients with NIDDM and mild hypertension. A 4-week run-in
      placebo period preceded the active 12-week treatment with perindopril (4-8 mg
      daily) or carvedilol (25-50 mg daily). Endothelial functions were assessed by
      evaluating the hemodynamic (mean blood pressure, leg blood flow) and rheological
      (platelet aggregation, blood viscosity, and blood filterability) responses to an
      intravenous bolus of 3 g L-arginine, the natural precursor of nitric oxide.
      RESULTS: Both perindopril and carvedilol significantly reduced mean blood
      pressure (P < 0.001) and increased leg blood flow (P < 0.05) to the same extent;
      blood filterability remained unchanged in both perindopril- and carvedilol
      treated groups. Carvedilol reduced platelet aggregation and blood viscosity
      significantly (P < 0.05) but perindopril did not. Before treatment, the
      hemodynamic and rheologic responses to L-arginine were significantly lower in
      patients (P < 0.05-0.01) than in 20 nondiabetic nonhypertensive control subjects.
      After 12 weeks of treatment, both drugs normalized the hemodynamic responses to L
      arginine. Platelet aggregation response to L-arginine was ameliorated by
      carvedilol and remained unchanged in the perindopril group. CONCLUSIONS: At the
      doses used, both drugs effectively reduce blood pressure and normalize the
      hemodynamic responses to L-arginine. The implications of the ameliorated
      endothelial function for the poor cardiovascular outlook of the NIDDM
      hypertensive patient need further assessment.

PMID- 9571357
TI  - Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled
      study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes
      Cardiovascular Disease Prevention (SENDCAP) Study.
AB  - OBJECTIVE: To determine whether serum lipid intervention, in addition to
      conventional diabetes treatment, could alter cardiovascular outcomes in type 2
      diabetes. RESEARCH DESIGN AND METHODS: There were 164 type 2 diabetic subjects
      (117 men, 47 women) without a history of clinical cardiovascular disease
      randomized to receive either bezafibrate or placebo daily on a double-blind basis
      in addition to routine diabetes treatment and followed prospectively for a
      minimum of 3 years. Serial biochemical and noninvasive vascular assessments,
      carotid and femoral artery B-mode ultrasound measurements, and those pertaining
      to coronary heart disease (CHD)--clinical history, the World Health Organization
      (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram
      (ECG)--were recorded. RESULTS: Bezafibrate treatment was associated with
      significantly greater reductions over 3 years in median serum triglyceride (-32
      vs. 4%, P = 0.001), total cholesterol (-7 vs. -0.3%, P = 0.004), and total-to-HDL
      cholesterol ratio (-12 vs. -0.0%, P = 0.001), and an increase in HDL cholesterol
      (6 vs. -2%, P = 0.02) as compared with placebo. There was a trend toward a
      greater reduction of fibrinogen (-18 vs. -6%, P = 0.08) at 3 years. No
      significant differences between the two groups were found in the progress of
      ultrasonically measured arterial disease. In those treated with bezafibrate,
      there was a significant reduction (P = 0.01, log-rank test) in the combined
      incidence of Minnesota-coded probable ischemic change on the resting ECG and of
      documented myocardial infarction. CONCLUSIONS: Improving dyslipidemia in type 2
      diabetic subjects had no effect on the progress of ultrasonically measured
      arterial disease, although the lower rate of "definite CHD events" in the treated
      group suggests that this might result in a reduction in the incidence of coronary
      heart disease.

PMID- 9571358
TI  - Plasma fibrinogen: a new factor of the metabolic syndrome. A population-based
      study.
AB  - OBJECTIVE: To evaluate whether hyperfibrinogenemia represents a component of the
      metabolic syndrome. RESEARCH DESIGN AND METHODS: A cross-sectional study was
      conducted on the relation between fibrinogen and the metabolic syndrome in a
      working population of 1,252 nondiabetic men, aged 35-64 years, randomly selected
      among all men participating in a health screening. We measured anthropometric
      characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total,
      LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more
      metabolic abnormalities (defined as being in the highest quartile of the
      distribution of diastolic blood pressure, plasma glucose, or triglycerides or
      being in the lowest quartile of HDL cholesterol) were considered to have the
      metabolic syndrome. RESULTS: Age-adjusted fibrinogen levels correlated
      significantly with BMI, waist-to-hip ratio, systolic and diastolic blood
      pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and
      HDL cholesterol (inversely). Subjects with the metabolic syndrome had
      significantly higher plasma fibrinogen levels than those without (285.1 +/- 1.9
      vs. 300.2 +/- 3.0 mg/dl, mean +/- SE, P = 0.0001). Plasma fibrinogen
      concentrations and the prevalence of hyperfibrinogenemia (defined as > or = 350
      mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to
      22% (P = 0.0024), respectively, across categories with an increasing number of
      metabolic disorders characterizing the syndrome (only one, any two, three or
      more). In multivariate analyses, both plasma insulin and the metabolic syndrome
      were significantly and independently associated with plasma fibrinogen.
      CONCLUSIONS: The finding suggests that hyperfibrinogenemia may be considered a
      component of the metabolic syndrome. This may also explain the increased
      cardiovascular risk associated with hyperinsulinemia/insulin resistance.

PMID- 9571359
TI  - Hypertension and diabetes and the Fosinopril versus Amlodipine Cardiovascular
      Events Trial (FACET). More ammunition against surrogate end points.

PMID- 9571360
TI  - International Diabetes Federation Meeting, 1997, and Metropolitan Diabetes
      Society of New York Meeting, November 1997. Approaches to treatment and other
      topics in type 1 diabetes; genetic heterogeneity of diabetes.

PMID- 9571361
TI  - Evaluation of the use of fasting plasma glucose as a new diagnostic criterion for
      diabetes in Asian Indian population.

PMID- 9571362
TI  - Assessing the antihyperglycemic effect of acarbose. Solid or liquid test meal?

PMID- 9571363
TI  - Gestational diabetes mellitus is associated with an increase in the total
      concentration of amylin molecules.

PMID- 9571364
TI  - A critical issue. Intensive insulin treatment and macrovascular disease.

PMID- 9571365
TI  - Diagnosis of diabetes in cystic fibrosis and thalassemia major.

PMID- 9571366
TI  - Changes in erythrocyte sorbitol concentrations measured using an improved assay
      system in patients with diabetic complications and treated with aldose reductase
      inhibitor.

PMID- 9571367
TI  - Glucose tolerance, insulin sensitivity, and the homeostasis model assessment
      method.

PMID- 9571368
TI  - Screening for gestational diabetes. What is the no-show rate?

PMID- 9571370
TI  - Constant infused glucose regimen during the recovery phase of diabetic
      ketoacidosis in children and adolescents with IDDM.

PMID- 9571369
TI  - Antibodies to GAD in elderly patients with previously diagnosed NIDDM.

PMID- 9571371
TI  - Case report. Pseudohepatotoxicity of metformin.

PMID- 9571372
TI  - Recent developments in the molecular characterization of Barrett's esophagus.
AB  - Barrett's esophagus, or specialized intestinal metaplasia, is a common condition
      associated with gastroesophageal reflux and an increased risk for adenocarcinoma
      of the esophagus and gastric cardia. Currently, clinical surveillance for early
      detection of adenocarcinoma relies on the histopathological assessment of
      dysplasia. In this review we present data from the published literature, and
      combine this with results from our own research, to address what is currently
      known about the environmental factors and the molecular changes thought to be
      important in the pathogenesis of Barrett's esophagus. The most important and well
      characterized molecular changes, preceding the development of dysplasia, are
      alterations in the p53 and erbB-2 genes and aneuploidy. These molecular changes,
      as well as environmental influences, such as the quality and quantity of
      gastroduodenal refluxate, may result in abnormal cell proliferation which in turn
      promotes further genetic abnormalities and deregulation of cell growth. The
      identification of molecular changes, in the context of predisposing environmental
      factors, will enhance our understanding of the malignant progression of Barrett's
      esophagus leading to more effective surveillance and treatment.

PMID- 9571373
TI  - Ulcerative colitis and colon cancer: more controversy than clarity.
AB  - Although it is generally accepted that the risk of colorectal cancer in patients
      with ulcerative colitis is increased compared with the general population, the
      management of this increased risk remains controversial. Patients with pancolitis
      of > 8 years duration should consider periodic colonoscopic surveillance or
      prophylactic colectomy. For patients unwilling to undergo prophylactic colectomy,
      colonoscopic surveillance annually or biennially is recommended. High-grade
      dysplasia or low-grade dysplasia in association with a lesion or mass is an
      indication for colectomy when confirmed by 2 pathologists. Repeat colonoscopic
      surveillance (in 3-6 months) or colectomy is recommended for confirmed low-grade
      dysplasia.

PMID- 9571374
TI  - Abnormalities of liver regeneration: a review.
AB  - Structural and functional changes during liver regeneration have been studied
      extensively in experimental animals following partial hepatectomy or hepatic
      injury induced by noxious substances. These observations have been extended to
      evaluate abnormalities of liver regeneration which contribute to chronic
      hepatitis, cirrhosis and/or liver cancer in man. This is facilitated by the
      simultaneous perfusion of flash frozen percutaneous biopsies or explanted liver
      in an acrylic chamber with tritiated thymidine and proline to evaluate DNA and
      collagen synthesis, respectively. Such investigations indicate that chronic liver
      damage is associated with replication of mesenchymal, ductular and parenchymal
      cells, accompanied by increased fibrogenesis. The regenerative response of the
      liver after noxious injury in experimental animals and man is associated with the
      release of cytokines, increase of growth response genes and change in telomerase
      activity. The ability to monitor morphological, genetic and biochemical
      parameters provides new information on the kinetics of the reparative process in
      hepatobiliary disease. Abnormal liver regeneration and its untoward effects
      including tumorigenesis may be modified by altering nutrients, blocking antigens
      or receptors, and inhibiting metabolites which regulate cell replication and
      collagen deposition.

PMID- 9571375
TI  - Management of bile duct stones in the era of laparoscopic cholecystectomy.
AB  - The development of laparoscopic cholecystectomy has transformed many aspects of
      gallstone disease management, particularly the care of patients with known or
      suspected bile duct stones. New obstacles to operative access to the bile duct
      have stressed the importance of accurate clinical prediction and detection of
      bile duct stones and led to increased reliance on nonsurgical approaches,
      especially pre- or postoperative endoscopic retrograde cholangiopancreatography
      and sphincterotomy, as well as spurring the development of new techniques such as
      laparoscopic common bile duct exploration. This work reviews the key features and
      rational usage of the endoscopic, laparoscopic and open surgical procedures, as
      well as other adjunct techniques, employed in the treatment of bile duct stones,
      emphasizing current options in the approach to this problem in the
      perilaparoscopic cholecystectomy setting. Management of bile duct stones in other
      special clinical circumstances and the potential future role of emerging
      technologies are also discussed.

PMID- 9571376
TI  - Upper respiratory tract complications of gastroesophageal reflux in adult and
      pediatric-age patients.
AB  - Upper airway complications of gastroesophageal reflux occur much less frequently
      than those abroad to the upper esophageal sphincter; however, laryngitis,
      laryngeal and/or tracheal stenosis, globus syndrome, oropharyngeal dysphagia,
      otitis media, sinusitis, and rhinitis can all be associated with significant
      morbidity and occasional mortality in both adult and pediatric patients. Sudden
      infant death and apparent life-threatening events, both found only in pediatric
      patients, are even less frequently associated with gastroesophageal reflux.
      Today, excellent diagnostic methods are available, such as proximal 24-hour pH
      probe evaluations or scintigraphy, making proper diagnosis much easier than
      previously. Although today's medical and surgical methods do not affect the
      underlying pathophysiology, they are frequently very effective in controlling
      signs and symptoms, allowing the patients to return to resume their normal life
      styles and livelihoods.

PMID- 9571378
TI  - Statistical methods in epidemiology: I. Statistical errors in hypothesis testing.
AB  - PURPOSE: Although scientific journal editors are making use of statisticians in
      the review process, the quality of statistical reporting in many journals remains
      poor. In many cases the problem for the scientist would appear to be a lack of
      understanding of basic statistics. The focus of the scientist is on showing 'p <
      0.05', when what is actually required is a statement about effect size and
      interval estimation. The aim of this paper is to show the inadequacy of reporting
      of results using p-values alone. This paper is the first in a series detailing
      common statistical methods, with a view to aiding potential authors in their
      statistical presentation of data. METHOD: A review of the basic hypothesis test,
      using examples from the author's own teaching experiences. RESULTS: Type I and
      type II errors are defined; the problem of multiple comparisons is highlighted;
      interval estimation is introduced. CONCLUSIONS: The case for considering the p
      value as an error probability is made which suggests ways of improving
      statistical presentation and thus expediting the statistical review process.

PMID- 9571377
TI  - Bile acid diarrhea.
AB  - Bile acids normally undergo enterohepatic circulation. When this circulation is
      interrupted, bile acids enter the colon in increased concentrations. Here, they
      produce Cl- secretion by a calcium- and cyclic AMP-dependent mechanism, resulting
      in diarrhea. Cholestasis may lead to serum bile acid concentrations high enough
      to produce colonic secretion by serosal surface effects. When resection or
      disease interferes with ileal function, the resulting diarrhea can be clearly
      attributed to bile acid malabsorption. In other states, such as
      postcholecystectomy diarrhea and idiopathic bile acid diarrhea, the role of bile
      acids is less well defined. 23-75Selena-25-homotaurocholic acid provides a way of
      tracing the metabolism of bile acids and their enterohepatic circulation in vivo.
      Metabolized similarly to natural bile acids, its circulation is easily traced by
      scintigraphy. Barium x-rays, serum concentrations of bile acids or bile acid
      intermediates, and tests of vitamin B12 absorption provide indirect measures of
      ileal function. Careful history and examination combined with one of many the
      available tests of ileal function allow a diagnosis. A therapeutic trial with a
      bile acid binding resin confirms the impression and treats the diarrhea.

PMID- 9571379
TI  - Work values: a comparison of non-disabled persons with persons with paraplegia.
AB  - A number of studies focus on factors that might explain the low level of
      employment of persons with paraplegia without questioning the social
      representations connected to work. Being employed is considered a priori as
      beneficial, constituting an important objective for rehabilitation. However
      sociologists have recently pointed out that work, as a means of self fulfilment,
      is a 'constructed' rather than a 'natural' category. The comparisons of the
      representations of work given by two groups: persons with paraplegia (n = 350),
      and non-disabled persons (n = 327) show that persons with paraplegia are more
      likely than non-disabled persons to consider work as a source of personal
      fulfilment and social recognition and less likely to positively value the fact of
      not-working. In addition, a demonstrated satisfaction with not working, among
      persons of working age, is clearly more significant among non-disabled persons
      than among persons with paraplegia. Among these, some of them who have generally
      made up their mind about not working declare that they feel satisfied being
      unoccupied. This satisfaction is explained, in part, by expressed representations
      of work. The authors suggest a reflection on the place of work in rehabilitation
      programmes.

PMID- 9571380
TI  - Determinants of self-efficacy among persons with spinal cord injuries.
AB  - The purpose of this study was to determine the factors affecting self-efficacy
      among persons with spinal cord injury (SCI). The study population consisted of
      105 persons with SCI who were discharged from one of eight hospitals in north
      central Alabama between October 1989 and September 1992. Data were derived from a
      retrospective acute-care medical record review and 12-month annual follow-up
      telephone interviews. The findings indicate that high self-efficacy is
      significantly associated with less severe neurological impairment, being white,
      employed at injury, having a high-school education or beyond, and having an
      unintentional injury. In terms of marital status our data indicate the odds of
      divorced persons having high self-efficacy are 8.2 (CL = 0.919, 74.1) times those
      of married persons. In addition, 64% of those who were divorced during the 12
      months after injury had high self-efficacy compared to 50% of those who were
      divorced prior to injury.

PMID- 9571381
TI  - A frequency and correlation analysis of motor deficits in Parkinson patients.
AB  - PURPOSE: The present study explored the frequency and pattern of functional motor
      problems of a group of Parkinson patients, as a first step towards developing a
      rational approach to rehabilitation intervention addressing the primary symptoms
      of the disease. METHOD: Sixty patients, consisting of 40% women and 60% men with
      a mean age of 63.5 years and of which 88% were taking L-dopa, underwent a number
      of standardized clinical tests including part III of the UPDRS. They were also
      interviewed about the frequency of motor problems occurring at home. RESULTS:
      Loss of trunk rotation as expressed in rolling in supine and reduced arm swing
      were the most frequently registered motor disorders (73%, 75%). Freezing at the
      start of, or during, walking was not observed during clinical testing but was
      frequently claimed to occur at home (48%, 23%). A broad spectrum of deficits
      regarding gait, posture, transfers and distal motor problems formed a cluster,
      which was strongly correlated with bradykinesia (p < 0.001). Principal component
      analysis identified four distinct problem areas: (1) axial motor performance; (2)
      akinetic gait problems; (3) rigidity; and (4) tremor. CONCLUSIONS: Parkinson
      patients, particularly in the later stages of the disease, presented with
      significant levels of functional disability which was mainly linked with the
      underlying impairment of bradykinesia.

PMID- 9571382
TI  - Rehabilitation of chronic low back pain using continuous epidural analgesia.
AB  - PURPOSE: Physical rehabilitation is one of the major forms of treatment of
      chronic low back pain. The ability of some patients to cooperate is limited by
      pain. Since 1992 continuous epidural analgesia has been combined with a physical
      rehabilitation programme for patients with chronic low back pain who have been
      unable to make progress with conventional physical rehabilitation due to severity
      of pain. METHOD: This study reports a series of 46 consecutive patients with
      chronic back pain admitted over a 6 month period to a 5-day inpatient
      rehabilitation programme. A lumbar epidural catheter was inserted and bupivacaine
      0.125% was infused at a rate that produced analgesia without sensory or motor
      deficit over a period of 5 days. An intensive mobilizing physiotherapy programme
      was instituted. Physical and psychological parameters were measured on day 1,
      after 1 week, after 1 month and after 1 year. RESULTS: Time to complete a 50 m
      walk, time from sitting to standing, and spinal flexion were improved at 1 week
      and 1 month, but only time to complete the walk remained improved at 1 year. In
      Goldberg's General Health Questionnaire 28 scores were improved for social
      dysfunction, somatic symptoms, anxiety and insomnia, and depression, at 1 week
      and 1 month but only social dysfunction remained improved at 1 year. Using a
      Visual Analogue Scale pain ratings were unaltered after 1 year. CONCLUSION:
      Continuous 5 day epidural analgesia combined with intensive physiotherapy may
      offer a means of initial rehabilitation of chronic low back pain. The initial
      benefit was most marked at 1 week, with benefit still evident after 1 month.
      However, the benefit decreased with time. This technique may be of value as part
      of a more comprehensive programme of physical and psychological rehabilitation.

PMID- 9571383
TI  - Genetic influences in antisocial personality and drug use disorders.
AB  - While an association between antisocial personality disorder (APD) and substance
      use disorder (SUD) has been frequently observed, the causes of the comorbidity
      remain unclear. Adoption and twin studies have found evidence of both genetic and
      environmental influences in APD and SUD. Therefore, comorbidity between APD and
      SUD may be the result of shared genetic influences, shared environmental
      influences, or a combination of the two. However, only a limited number of
      adoption and twin studies have addressed this issue and the results have not been
      conclusive. In future studies, a distinction should be made between alcohol and
      drug abuse and between juvenile and adult APD symptoms. Twin samples of adequate
      size would allow use of structural equation analytical methods for estimation of
      the relative magnitude of genetic and environmental influences shared between the
      two conditions, as well as influences contributing to each specifically. Results
      would be highly relevant for the clinical setting as well as for efforts to
      identify the genes involved in either trait.

PMID- 9571384
TI  - Reliability of self-reported antisocial personality disorder symptoms among
      substance abusers.
AB  - It is estimated that from 20 to 60% of substance abusers meet criteria for
      Antisocial Personality Disorder (APD). An accurate and reliable diagnosis is
      important because persons meeting criteria for APD, by the nature of their
      disorder, are less likely to change behaviors and more likely to relapse to both
      substance abuse and high risk behaviors. To understand more about the reliability
      of the disorder and symptoms of APD, the Diagnostic Interview Schedule Version
      III-R (DIS) was administered to 453 substance abusers ascertained from treatment
      programs and from the general population (St Louis Epidemiological Catchment Area
      (ECA) follow-up study). Estimates of the 1 week, test-retest reliability for the
      childhood conduct disorder criterion, the adult antisocial behavior criterion,
      and APD diagnosis fell in the good agreement range, as measured by kappa. The
      internal consistency of these DIS symptoms was adequate to acceptable. Individual
      DIS criteria designed to measure childhood conduct disorder ranged from fair to
      good for most items; reliability was slightly higher for the adult antisocial
      behavior symptom items. Finally, self-reported 'liars' were no more unreliable in
      their reports of their behaviors than 'non-liars'.

PMID- 9571385
TI  - Antisocial behavioral syndromes among residential drug abuse treatment clients.
AB  - We compared residential addictions treatment clients meeting full criteria for
      antisocial personality disorder (ASPD+) with those reporting syndromal levels of
      antisocial behavior only in adulthood (AABS+) on demographics, antisocial
      symptomatology, drug history, axis I comorbidity and characteristics of index
      treatment episode. We examined these issues in the sample as a whole, as well as
      separately in male and female respondents. Among both men and women, ASPD+
      initiated their antisocial behavior earlier, met more ASPD criteria and endorsed
      more violent symptoms, than AABS+. Male ASPD+ also met criteria for more lifetime
      axis I diagnoses and reported more years of drug involvement than male AABS+.
      Trends were observed toward poorer retention in treatment among ASPD+ than among
      AABS+ participants of both genders randomized to a planned duration of 180 days,
      but retention did not differ between ASPD+ and AABS+ randomized to a planned
      duration of 90 days. Our findings, which replicate and extend previously
      published results, carry potential implications for treatment programming and for
      the nosology of ASPD.

PMID- 9571386
TI  - Prediction of 7 months methadone maintenance treatment response by four measures
      of antisociality.
AB  - Zero-order correlational and simultaneous regression analyses were performed to
      ascertain the comparative validity of four measures of antisociality for
      predicting the initial 7 months treatment response of 193 male methadone
      maintenance (MM) patients. Predictor variables were the number of childhood
      conduct disorder (CD) behaviors, number of adult antisocial personality disorder
      (A-APD) behaviors, the revised Psychopathy Checklist (PCL-R) score and the
      revised California Psychological Inventory-Socialization (CPI-So) scale score.
      The outcome measures were completion/noncompletion of 7 months of treatment,
      percent positive during-treatment of cocaine, opiate and benzodiazepine urine
      toxicologies, and change from baseline to 7 months follow-up in seven Addiction
      severity index (ASI) composite scores (CSs). All four measures of antisociality
      were significantly correlated with treatment noncompletion, although only the PCL
      R score was significant in the predictor model. The PCL-R predicted more positive
      cocaine urines. At the individual level, both PCL-R and CPI-So were associated
      with more positive benzodiazepine urines, but neither contributed a significant
      amount of variance when both were entered in the model. None of the predictors
      were significantly associated with self reported improvement in the CSs. The PCL
      R and CPI-So were more successful in predicting outcomes than the two behavior
      based measures.

PMID- 9571387
TI  - Substance-dependent, conduct-disordered adolescent males: severity of diagnosis
      predicts 2-year outcome.
AB  - Most delinquent youths have conduct disorder (CD), often with comorbid substance
      use disorder (SUD), attention-deficit/hyperactivity disorder (ADHD) and
      depression. Some youths' conduct problems later abate, while those of others
      persist into adult antisocial personality disorder. Earlier CD onset and ADHD
      reportedly predict persisting antisocial problems, but predictors of persisting
      SUD are poorly understood. Males aged 13-19 years (n = 89), most referred by
      criminal justice and social service agencies, received residential treatment for
      comorbid CD and SUD. They had diagnostic assessments for SUD at intake and for
      CD, ADHD, and depression (as well as drug-use assessments) at intake and 6, 12
      and 24 months later. At intake nearly all had DSM-III-R substance dependence
      (usually on alcohol and marijuana) and CD with considerable violence and
      criminality. The 2-year follow-ups revealed improvements in criminality, CD,
      depression and ADHD, but substance use remained largely unchanged. Various
      aspects of conduct, crime and substance outcomes at 2 years were predicted by
      intake measures of intensity of substance involvement, and by CD severity and
      onset age, but not by severity of either ADHD or depression, nor by treatment
      duration. Earlier CD onset, more severe CD and more drug dependence predicted
      worse outcomes, supporting the validity of these diagnoses in adolescents.

PMID- 9571388
TI  - Cocaine users with antisocial personality improve HIV risk behaviors as much as
      those without antisocial personality.
AB  - Previous work has documented that antisocial personality disorder (APD) is
      associated with increased rates of HIV risk behaviors and with worse substance
      abuse treatment outcomes. The question addressed by this paper is whether cocaine
      users with APD respond to an HIV risk-reduction intervention as well as cocaine
      users without the disorder. The study subjects were 333 cocaine users followed up
      at 18 months as part of a NIDA-funded treatment demonstration project. The total
      sample improved across a wide range of HIV risk behaviors. Improving
      significantly (P < 0.05) from baseline to the 18-month follow-up were several
      drug-related behaviors: cocaine use; current cocaine dependence; use of drugs
      other than cocaine drug injection; injection equipment sharing; and use of
      syringes that were not cleaned. Several sex-related HIV risk behaviors also
      improved significantly: having multiple sex partners; being intoxicated during
      sex; giving drugs for sex; receiving money for sex; and receiving drugs for sex.
      When the sample was stratified by APD status, very similar improvement was seen
      in respondents with and without APD. To examine further the relationship of APD
      to change in HIV risk behaviors, separate logistic regression models of improving
      and worsening HIV risk behaviors were tested. What the authors found was no
      association of APD with improvement in HIV risk behaviors but a significant
      association of APD with worsening HIV risk behaviors. It appears that cocaine
      users with APD improve their HIV risk behaviors just as much as those without APD
      but may be at higher HIV risk for the development of such behaviors.

PMID- 9571389
TI  - Preliminary evidence of good treatment response in antisocial drug abusers.
AB  - Antisocial personality disorder (APD) is a chronic debilitating condition
      strongly associated with the development and maintenance of severe drug and
      alcohol use disorder. The overlap of these problems is associated with high rates
      of personal and social suffering. Available literature consistently point to this
      as a population in need of effective clinical services. The present study reports
      preliminary data from a controlled clinical trial aimed at improving the
      treatment outcomes of antisocial drug abusers using an intensive behavioral
      approach relying upon a highly structured contingency management intervention.
      Drug abusers in methadone substitution therapy (n = 40) were assessed for APD and
      other psychiatric and substance use problems. Patients were randomly assigned to
      an experimental (n = 20) or control (n = 20) condition following stratification
      on demographic and selected clinical variables (baseline drug use, evidence of
      other non-substance use psychiatric diagnoses). Treatment outcome data are
      presented for the first 17 weeks of participation in the study (4 weeks baseline
      and 13 weeks randomized treatment), including results of weekly urine drug
      testing and monthly self-reports of drug use and other psychosocial problems.
      Patients in both study conditions attained generally good outcomes. These early
      results suggest that antisocial drug abusers can respond positively to drug abuse
      treatments with a behavioral focus, but fail to support superior effectiveness
      for the more intensive intervention used in the experimental condition.

PMID- 9571391
TI  - Oesophageal mucosal diseases in the elderly.
AB  - Diseases of the oesophageal mucosa are particularly prevalent in the elderly
      population and may present with various symptoms, such as heartburn, dysphagia or
      chest pain. Recent technological advances, such as endoscopy, ambulatory pH
      monitoring and radiological imaging, have allowed for a more accurate diagnosis
      and assessment of disease severity. Depending on the leading presenting symptom,
      empirical medical therapy or stepwise diagnostic tests may be used. Elderly
      patients with mild reflux symptoms respond well to over-the-counter antacids,
      acid suppressants or prescription prokinetic drugs. Those with more severe
      gastrooesophageal reflux disease and Barrett's oesophagus benefit from powerful
      acid suppressive therapy to relieve symptoms, heal the mucosal damage and prevent
      complications. Long term, cost-effective pharmacological therapies are constantly
      being defined. Because of the widespread utilisation of medications in the
      elderly, drug-induced oesophageal injury should always be considered and
      prevented. An increasing number of immunocompromised elderly patients are
      diagnosed and successfully treated for infectious oesophagitis. Overall, for most
      elderly patients, when the diagnosis is made correctly, modern medical and/or
      surgical treatments yield maximal therapeutic benefit and improve quality of
      life.

PMID- 9571390
TI  - The role of nitric oxide in neurodegeneration. Potential for pharmacological
      intervention.
AB  - Nitric oxide (NO) is involved in important physiological functions of the CNS,
      including neurotransmission, memory and synaptic plasticity. Depending on the
      redox state of NO, it can act as a neurotoxin or it can have a neuroprotective
      action. Data suggest that NO may have a role in the pathogenesis of
      neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and
      Huntington's disease. Additionally, these data indicate that inhibitors of the NO
      synthesising enzyme, NO synthase, may be useful as neuroprotective agents in
      these diseases. In animal models, NOS inhibitors have been shown to prevent the
      neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and
      other dopaminergic toxins. However, the clinical effects of NOS inhibitors remain
      unknown.

PMID- 9571393
TI  - Capromab pendetide. A review of its use as an imaging agent in prostate cancer.
AB  - Capromab pendetide, radiolabelled with indium-111, is a radioimmunoscintigraphic
      imaging agent used in patients with prostate cancer. It consists of a murine
      monoclonal antibody (7E11-C5.3) covalently jointed to a linker-chelator molecule.
      7E11-C5.3 is thought to be directed against the intracellular domain of human
      prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein expressed
      by prostate epithelial cells. The diagnostic utility of capromab pendetide has
      been investigated in 2 distinct patient groups. In patients with untreated
      prostate cancer at high risk for pelvic lymph node metastases, capromab pendetide
      imaging had respective sensitivities and specificities of 52 and 96% in 1 study
      and 62 and 72% in another, as confirmed by pelvic lymph node dissection biopsy
      results. In patients with suspected occult recurrent or residual disease after
      prostatectomy, capromab pendetide had respective sensitivities and specificities
      of 49 and 71% in 1 study and 77 and 35% in another for detection of cancer in the
      prostate bed. Almost half of these patients also had evidence of lesions outside
      the prostate fossa (usually in the pelvic and abdominal lymph nodes) according to
      immunoscintigraphic scans, but too few cases were confirmed to allow an
      evaluation of capromab pendetide. Four per cent of patients who received single
      doses of capromab pendetide experienced adverse events. Elevated bilirubin
      levels, hypertension and hypotension each affected 1% of patients and elevated
      liver enzymes and injection site reactions < 1% of patients. Detectable human
      anti-mouse antibodies were reported in 8% of patients after a single dose of
      capromab pendetide and in 19% of patients after repeat infusions. CONCLUSIONS:
      Capromab pendetide offers improved sensitivity in the detection of prostate
      cancer over other noninvasive techniques. When used in conjunction with other
      techniques, it offers the possibility of defining the extent of localised and
      metastatic disease, thereby refining patient management.

PMID- 9571392
TI  - Age-related changes in cobalamin (vitamin B12) handling. Implications for
      therapy.
AB  - Cobalamin (vitamin B12) deficiency is more common in the elderly than in younger
      patients. This is because of the increased prevalence of cobalamin malabsorption
      in this age group, which is mainly caused by (autoimmune) atrophic body
      gastritis. Cobalamin supplementation is affordable and nontoxic, and it may
      prevent irreversible neurological damage if started early. Elderly individuals
      with cobalamin deficiency may present with neuropsychiatric or metabolic
      deficiencies, without frank macrocytic anaemia. An investigation of symptoms
      and/or signs includes the diagnosis of deficiency as well as any underlying
      cause. Deficiency states can still exist even when serum cobalamin levels are
      higher than the traditional lower reference limit. Cobalamin-responsive
      elevations of serum methylmalonic acid (MMA) and homocysteine are helpful
      laboratory tools for the diagnosis. The health-related reference ranges for
      homocysteine and MMA appear to vary with age and gender. Atrophic body gastritis
      is indirectly diagnosed by measuring serum levels of gastrin and pepsinogens, and
      it may cause dietary cobalamin malabsorption despite a normal traditional
      Schilling's test. The use of gastroscopy may also be considered to diagnose
      dysplasia, bacterial overgrowth and intestinal villous atrophy in healthy
      patients with atrophic body gastritis or concomitant iron or folic acid
      deficiency. Elderly patients respond to cobalamin treatment as fully as younger
      patients, with complete haematological recovery and complete or good partial
      resolution of neurological deficits. Chronic dementia responds poorly but should,
      nevertheless, be treated if there is a metabolic deficiency (as indicated by
      elevated homocysteine and/or MMA levels). Patients who are at risk from cobalamin
      deficiency include those with a gastrointestinal predisposition (e.g. atrophic
      body gastritis or previous partial gastrectomy), autoimmune disorders [type 1
      (insulin-dependent) diabetes mellitus and thyroid disorders], those receiving
      long term therapy with gastric acid inhibitors or biguanides, and those
      undergoing nitrous oxide anaesthesia. To date, inadequate cobalamin intake has
      not proven to be a major risk factor. Intervention trials of cobalamin, folic
      acid and pyridoxine (vitamin B6) in unselected elderly populations are currently
      under way.

PMID- 9571395
TI  - Raloxifene.
AB  - Raloxifene is a selective estrogen receptor modulator which mimics the effects of
      estrogens on bone and blood lipid levels without stimulatory effects on the
      breast or uterus. Raloxifene inhibits estrogen-dependent proliferation of human
      breast cancer cells in vitro and development of induced mammary tumours in rats
      in vivo. Raloxifene inhibits bone resorption induced by estrogen deficiency in
      murine and human studies and lowers serum cholesterol levels. In clinical studies
      in postmenopausal women, raloxifene 60 mg/day for 2 years significantly increased
      bone mineral density compared with placebo. In comparative clinical studies,
      raloxifene 60 mg/day had more modest effects than conjugated estrogens 0.625
      mg/day on bone resorption and formation parameters and appeared to be less
      effective in increasing bone mineral density. In older postmenopausal women with
      existing bone fractures, raloxifene 60 or 120 mg/day for 1 year produced modest
      increases in bone mineral density. The most common treatment-related adverse
      events in raloxifene recipients were hot flushes and leg cramps. The risk of
      venous thromboembolic events is increased during raloxifene therapy. In contrast
      with conjugated estrogens 0.625 mg/day, raloxifene 200 or 600 mg/day for 8 weeks
      or 150 mg/day for 1 year did not produce endometrial proliferation.

PMID- 9571397
TI  - Magnetic resonance imaging of the shoulder.

PMID- 9571398
TI  - Arthroscopic acromioplasty: indications and technique.

PMID- 9571399
TI  - Arthroscopic subacromial decompression--avoidance of complications and
      enhancement of results.

PMID- 9571400
TI  - Arthroscopic distal clavicle resection.

PMID- 9571394
TI  - Paclitaxel. An update of its use in the treatment of metastatic breast cancer and
      ovarian and other gynaecological cancers.
AB  - The antitumour agent paclitaxel has proved to be effective for the treatment of
      patients with metastatic breast or ovarian cancer, and limited data also indicate
      its clinical potential in patients with cervical or endometrial cancer. The
      regimen of paclitaxel administration has varied in clinical trials, the most
      common including a dosage of between 135 and 250 mg/m2 administered over an
      infusion period of 3 or 24 hours once every 3 weeks. Promising results have been
      achieved in phase I/II trials of a weekly regimen of paclitaxel (60 to 175
      mg/m2). The objective response rate in patients with metastatic breast cancer
      (either pretreated or chemotherapy-naive) is generally between 20 and 35% with
      paclitaxel monotherapy, which compares well with that of other current treatment
      options including the anthracycline doxorubicin. Combination therapy with
      paclitaxel plus doxorubicin appears superior to treatment with either agent alone
      in terms of objective response rate and median duration of response. However,
      whether combination therapy also provides a survival advantage remains unclear;
      recent results of a phase III study indicate that it does not. Paclitaxel is also
      a useful second-line option in some patients with anthracycline-resistant
      disease. Combination therapy with paclitaxel and cisplatin has proved highly
      effective as first-line therapy for patients with advanced ovarian cancer,
      showing superior efficacy to cyclophosphamide/cisplatin in terms of progression
      free survival time and median duration of survival. Combination therapy with
      paclitaxel and carboplatin has also shown promising results. Paclitaxel
      monotherapy is a useful second-line option for patients with platinum-refractory
      metastatic ovarian cancer (objective response rates have ranged from 15 to 48%).
      The major dose-limiting adverse events associated with paclitaxel include
      myelotoxicity and peripheral neuropathy. Paclitaxel has acceptable tolerability
      in most patients, although adverse events are common. CONCLUSION: Paclitaxel
      generally appears to be as effective as other antineoplastic agents used in the
      treatment of metastatic breast cancer, including doxorubicin. Importantly, it is
      a useful second-line option for some patients with anthracycline-resistant
      disease. Combination therapy with both paclitaxel and doxorubicin is a highly
      effective first-line option for metastatic breast cancer; however, recent results
      indicate no survival advantage versus monotherapy. Paclitaxel is a valuable agent
      for second-line treatment of patients with platinum-refractory metastatic ovarian
      cancer and, when combined with cisplatin or carboplatin, is recommended as first
      line therapy for this disease.

PMID- 9571401
TI  - Biomechanics of rotator cuff repair: converting the ritual to a science.

PMID- 9571402
TI  - Combined arthroscopic and open treatment of tears of the rotator cuff.

PMID- 9571403
TI  - Arthroscopic rotator cuff repair: current indications, limitations, techniques,
      and results.

PMID- 9571404
TI  - The treatment of stiffness of the shoulder after repair of the rotator cuff.

PMID- 9571405
TI  - The treatment of failed rotator cuff repairs.
AB  - Results following surgical management of failed rotator cuff tears are clearly
      inferior to those obtained in the treatment of primary repairs. Conservative
      management may be the treatment of choice in selected patients with failed
      rotator cuff repairs. The primary goal for revision rotator cuff surgery should
      be relief of pain, not improvement in function. If the level of pain is
      manageable, and the patient is functioning with respect to activities of daily
      living, additional surgery may not be helpful. As there are multiple etiologies
      associated with failure of the initial repair, each patient should be carefully
      evaluated on an individual basis to determine if a subsequent procedure would be
      appropriate. Repeat repair is more likely to succeed in patients with an intact
      and functioning deltoid, an intact lateral portion of the acromion, and good
      quality of rotator cuff tissue. Conversely, patients who have had a lateral or
      radical acromionectomy, a detached or nonfunctioning deltoid, or poor quality of
      remaining rotator cuff tissue are less likely to have a successful result after
      repeat repair. It is evident that some of the factors associated with failure are
      avoidable. As the best chance for a successful result is at the time of the
      primary repair, the following points will briefly review these factors. The skin
      incision should be made in the flexion creases which are perpendicular to the
      deltoid fibers. The deltoid origin should be meticulously protected during the
      repair and lateral or radical acromionectomy should not be performed. Adequate
      anterior acromioplasty is essential for removal of the impingement lesion and to
      prevent subsequent wear on the repaired cuff tendon. The acromioclavicular joint
      should be evaluated preoperatively and treated as indicated at the time of the
      surgery. Adequate release of adhesions and mobilization of rotator cuff tissue
      should be performed using the coracohumeral ligament release and interval slide
      when necessary. The rotator cuff should be repaired to bone using tendon to bone
      sutures and/or secure suture anchors. In large and massive tears, there appears
      to be a role for the reattachment of the coracohumeral ligament. Early phase I
      range of motion should be initiated following rotator cuff repair and early
      resistance exercise with weights should be avoided.

PMID- 9571406
TI  - Failed repair of the rotator cuff: evaluation and treatment of complications.

PMID- 9571407
TI  - Instability of the shoulder: complex problems and failed repairs: Part I.
      Relevant biomechanics, multidirectional instability, and severe glenoid loss.

PMID- 9571408
TI  - Instability of the shoulder: complex problems and failed repairs: Part II. Failed
      repairs.

PMID- 9571409
TI  - Current concepts of shoulder arthroplasty.
AB  - Shoulder arthroplasty is an accepted treatment for certain proximal humerus
      fractures and for glenohumeral arthritis. The indications for shoulder
      arthroplasty are fairly well defined and the outcomes are predictable and highly
      successful. However, it is a technically demanding surgical procedure, with which
      few orthopaedic surgeons gain much experience. Most of the currently available
      implant systems are modifications of the original unconstrained components that
      were introduced by Neer. Current issues of controversy include implant
      modularity, glenohumeral mismatch, implant fixation, and the role of glenoid
      replacement in outcome.

PMID- 9571410
TI  - Treatment of proximal humerus fracture malunion with prosthetic arthroplasty.

PMID- 9571411
TI  - Management of the unstable prosthetic shoulder arthroplasty.
AB  - Instability is the most common complication of shoulder arthroplasty. An
      understanding of the predisposing factors for developing instability is critical
      to the avoidance of this complication. Soft-tissue balance and proper component
      positioning must be attained during the index procedure to minimize the risk of
      developing postoperative instability. Once the shoulder does become unstable, the
      reason for the instability must be determined. Is the instability secondary to
      soft-tissue imbalance, component malposition, bony deformity, or a combination of
      these? Next, a decision must be made as to how to treat the instability.
      Nonsurgical treatment may be tried if no obvious cause is present. However, if
      the instability fails to resolve or recurs, surgical intervention should be
      undertaken early. If the instability is not treated, it may result in loosening
      of the prosthesis and early wear of the components. Once surgical intervention is
      undertaken, all elements of the instability must be recognized and treated.

PMID- 9571412
TI  - Surgical management of the extensor mechanism of the elbow.

PMID- 9571413
TI  - Complex instability of the elbow.

PMID- 9571414
TI  - Tennis elbow.

PMID- 9571415
TI  - Fractures of the radial head and related instability and contracture of the
      forearm.
AB  - Displaced fractures of the radial head that require reduction or excision are
      often associated with longitudinal instability. Where possible (type II), these
      fractures should be stabilized with rigid internal fixation In cases in which the
      initial displacement reflects complete dissociation, supplemental stabilization
      and repair may be required. Particular attention must be paid to the
      posterolateral collateral ligament, the interosseous ligament of the forearm, and
      ligaments at the distal radioulnar joint.

PMID- 9571416
TI  - Soft-tissue injuries of the hand in the athlete.

PMID- 9571417
TI  - Fractures in the hand in athletes.

PMID- 9571418
TI  - Intra-articular fractures of the distal radius: contemporary perspectives.

PMID- 9571419
TI  - Wrist instability.

PMID- 9571420
TI  - Distal radioulnar joint instability.

PMID- 9571421
TI  - Ulnar-sided wrist pain and instability.
AB  - A variety of lesions have been associated with ulnar-sided wrist pain and/or VISI
      instability. A staging system for ulnar-sided perilunate instability describes
      progressive disruptions associated with lunotriquetral dissociation that can lead
      to VISI instability and emphasizes the importance of the dorsal radiocarpal
      ligament in preventing VISI instability. Previous studies have emphasized
      association between type II carpal morphology and arthrosis at the proximal pole
      of the hamate, which was identified as the most common location of arthrosis in
      the wrist. The pisotriquetral joint is another common site of degenerative
      changes. A better understanding of the normal anatomy and kinematics of the ulnar
      side of the wrist will better enable physicians to identify and treat problems in
      the ulnar aspect of the wrist.

PMID- 9571422
TI  - Radial-sided carpal instability.

PMID- 9571423
TI  - Periprosthetic fractures of the acetabulum during and following total hip
      arthroplasty.

PMID- 9571424
TI  - Periprosthetic fractures of the femur: principles of prevention and management.

PMID- 9571425
TI  - Periprosthetic fracture of the femur after total hip arthroplasty: treatment and
      results to date.

PMID- 9571426
TI  - Periprosthetic hip and knee fractures: the scope of the problem.
AB  - This review covers the present incidence, site, and outcome of periprosthetic
      fractures of the hip and the knee. Fractures can occur intraoperatively or
      postoperatively as an early or a late complication. Late postoperative fractures
      are related to osteolysis secondary to wear debris. These late fractures will
      become more prevalent with time. Intraoperative fractures can be avoided by
      careful technique and improved instrument design. Fractures can affect the
      acetabulum, femur, and trochanter of hip replacements: and the femur, tibia, and
      patella of knee replacements. The femur is most commonly involved for both
      joints. Stress fractures have been described as a rare complication of both sites
      of arthroplasty. If the fracture is recognized and the bone stock is good, a good
      outcome can be achieved if rigid fixation is obtained Unfortunately poor bone
      stock is often present, leading to late periprosthetic fractures, which
      compromise the outcome.

PMID- 9571427
TI  - The role of allografts in the treatment of periprosthetic femoral fractures.

PMID- 9571428
TI  - Impaction morcellized allografting and cement.

PMID- 9571429
TI  - Neurovascular injury associated with hip arthroplasty.

PMID- 9571430
TI  - Diagnosis of infection following total hip arthroplasty.

PMID- 9571431
TI  - Treatment of infection at the site of total hip replacement.

PMID- 9571432
TI  - Osteolysis: cause and effect.

PMID- 9571433
TI  - Osteolysis: surgical treatment.

PMID- 9571434
TI  - Prevention and treatment of venous thromboembolic disease complications in
      primary hip arthroplasty patients.
AB  - This chapter is a brief and incomplete overview of a rapidly changing field. The
      following points are helpful for the management of hip arthroplasty patients.
      There is no clinically significant difference between warfarin and enoxaparin
      prophylaxis in terms of efficacy (venographic or clinical events) and safety. Hip
      arthroplasty patients should receive warfarin or enoxaparin for at least 7 to 10
      days postoperatively. There is a high rate of postdischarge venographic DVT even
      if prophylaxis is used for 7 to 10 days after surgery. There is a 2% rate of
      postdischarge symptomatic DVT if prophylaxis is used for 7 to 10 days after
      surgery. There is a 0.1% rate of postdischarge fatal PE at 90 days
      postoperatively if prophylaxis is used for 7 to 10 days after surgery. The value
      of routine predischarge surveillance for DVT is not clear at this moment.

PMID- 9571435
TI  - Algorithm for anterior knee pain.

PMID- 9571436
TI  - Patellar instability in the school age athlete.

PMID- 9571437
TI  - Anterior cruciate ligament injuries in the skeletally immature patient.
AB  - Anterior cruciate ligament injury in the skeletally immature is becoming
      increasingly recognized and reported. History taking and physical examination
      based on the principles of ACL injuries in adults, with adjuncts such as
      arthroscopy and MRI, are effective in diagnosing ACL injury in the young patient.
      Evaluation of the young patient's true level of skeletal immaturity by comparison
      with family growth history, examination for signs of sexual maturity, and
      radiographic evaluation is critical. The risk of physeal damage with surgical
      treatment is related to the immaturity of the distal femoral and proximal tibial
      physes. The functional results of nonsurgical treatment of ACL injury, either as
      an attempt at definitive treatment or as a temporizing plan until skeletal
      maturity occurs, are poor and the risks of reinjury and further meniscal and
      cartilage damage are significant. Surgical treatment for primary repair or extra
      articular reconstruction alone has not proven to be efficacious. In the
      adolescent patient who is approaching skeletal maturity, risk of physeal injury
      is low and intra-articular reconstruction can be performed as in the adult
      patient. Results with respect to decreased laxity and return to athletic
      activities mirror those described in adults. In patients with significant growth
      remaining, however, surgical treatment carries much higher risks of physeal
      damage and subsequent deformity. Yet, as noted above, intra-articular
      reconstruction in truly skeletally immature patients using a soft-tissue graft
      through a transphyseal tibial tunnel of moderate or small diameter and the over
      the-top position on the femur has not been shown to cause early physeal closure,
      limb-length discrepancy, or angular deformity. In humans, the maximum diameter of
      graft tunnel that will not cause physeal closure has not been determined Animal
      studies have shown that the tibial physis can be very sensitive to drilling.
      Therefore it is wise to use moderate tunnel diameters. Bone-patellar tendon-bone
      grafts have been used with success in patients closer to skeletal maturity. Their
      use has not been reported in the very skeletally immature knee and cannot be
      recommended because of the presumed high risk of physeal closure with a bone plug
      traversing the physis. It is hoped that improved understanding of the ACL injury
      in the skeletally immature patient will provide treatment options that will
      restore enduring knee function and prevent early arthrosis.

PMID- 9571438
TI  - Revision anterior cruciate ligament reconstruction.

PMID- 9571439
TI  - Management of chronic posterolateral rotatory instability of the knee: surgical
      technique for the posterolateral corner sling procedure.

PMID- 9571440
TI  - The role of allografts in repair and reconstruction of knee joint ligaments and
      menisci.

PMID- 9571441
TI  - Running injuries: a biomechanical approach.

PMID- 9571442
TI  - Running injuries of the knee.
AB  - Running injuries of the knee are very common. Significant risk factors for
      injuries are high mileage, previous injury, and rapid change in the program.
      Because two thirds of running injuries are training related, training is an
      important aspect of the history. In the case of knee injuries, the examination
      must include the entire lower extremity and not concentrate only on the knee.
      Most running injuries, whether in the knee or elsewhere, are managed
      conservatively but, as with any condition, surgery is sometimes indicated. During
      rehabilitation from injury or surgery, the physician must supervise the
      rehabilitation and the return to running to avoid reinjury.

PMID- 9571443
TI  - Achilles tendon problems in runners.

PMID- 9571444
TI  - High tibial osteotomy and distal femoral osteotomy for valgus or varus deformity
      around the knee.

PMID- 9571445
TI  - Periprosthetic fractures adjacent to total knee implants: treatment and clinical
      results.

PMID- 9571446
TI  - Fractures of the femur, tibia, and patella after total knee arthroplasty:
      decision making and principles of management.

PMID- 9571447
TI  - Cartilage and bone development.

PMID- 9571448
TI  - Autocrine regulation of articular cartilage.

PMID- 9571449
TI  - Articular cartilage: tissue design and chondrocyte-matrix interactions.
AB  - The unique biologic and mechanical properties of articular cartilage depend on
      the design of the tissue and the interactions between the chondrocytes and the
      matrix that maintain the tissue. Chondrocytes form the macromolecular framework
      of the tissue matrix from three classes of molecules: collagens, proteoglycans,
      and noncollagenous proteins. Type II, IX, and XI collagens form a fibrillar
      meshwork that gives the tissue as form and tensile stiffness and strength. Type
      VI collagen forms part of the matrix immediately surrounding the chondrocytes and
      may help the chondrocytes to attach to the macromolecular framework of the
      matrix. Large aggregating proteoglycans (aggrecans) give the tissue its stiffness
      to compression and its resilience and contribute to its durability. Small
      proteoglycans, including decorin, biglycan, and fibromodulin, bind to other
      matrix macromolecules and thereby help to stabilize the matrix. They may also
      influence the function of the chondrocytes and bind growth factors. Anchorin CII,
      a noncollagenous protein, appears to help to anchor chondrocytes to the matrix.
      Cartilage oligomeric protein may have value as a marker of turnover and
      degeneration of cartilage, and other noncollagenous proteins, including tenascin
      and fibronectin, can influence interactions between the chondrocytes and the
      matrix. The matrix protects the cells from injury due to normal use of the joint,
      determines the types and concentrations of molecules that reach the tells and
      helps to maintain the chondrocyte phenotype. Throughout life, the tissue
      undergoes continual internal remodeling as the cells replace matrix
      macromolecules lost through degradation. The available evidence indicates that
      normal matrix turnover depends on the ability of chondrocytes to detect
      alterations in the macromolecular composition and organization of the matrix,
      including the presence of degraded molecules, and to respond by synthesizing
      appropriate types and amounts of new molecules. In addition, the matrix acts as a
      signal transducer for the cells. Loading of the tissue due to use of the joint
      creates mechanical, electrical, and physicochemical signals that help to direct
      the synthetic and degradative activity of chondrocytes. A prolonged severe
      decrease in the use of the joint leads to alterations in the composition of the
      matrix and eventually to loss of tissue structure and mechanical properties,
      whereas use of the joint stimulates the synthetic activity of chondrocytes and
      possibly the internal tissue remodeling Aging leads to alterations in the
      composition of the matrix and the activity of the chondrocytes, including the
      ability of the cells to respond to a variety of stimuli such as growth factors.
      These alterations may increase the probability of degeneration of the cartilage.

PMID- 9571450
TI  - Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and
      transplantation.
AB  - The degeneration of articular cartilage as part of the clinical syndrome of
      osteoarthritis is one of the most common causes of pain and disability in middle
      aged and older people. The strong correlation between increasing age and the
      prevalence of osteoarthritis, and recent evidence of important age-related
      changes in the function of chondrocytes, suggest that age-related changes in
      articular cartilage can contribute to the development and progression of
      osteoarthritis. Although the mechanisms responsible for osteoarthritis remain
      poorly understood lifelong moderate use of normal joints does not increase the
      risk. Thus, the degeneration of normal articular cartilage is not simply the
      result of aging and mechanical wear. However, high-impact and torsional loads may
      increase the risk of degeneration of normal joints, and individuals who have an
      abnormal joint anatomy, joint instability, disturbances of joint or muscle
      innervation, or inadequate muscle strength or endurance probably have a greater
      risk of degenerative joint disease. Recent work has shown the potential for the
      restoration of an articular surface. Currently, surgeons frequently debride
      joints and penetrate subchondral bone as well as perform osteotomies, with the
      intent of decreasing symptoms and restoring or maintaining a functional articular
      surface. The results of these procedures vary considerably among patients.
      Clinical and experimental work has shown the important influence of loading and
      motion on the healing of articular cartilage and joints. Experimental studies
      have revealed that transplantation of chondrocytes and mesenchymal stem cells;
      use of periosteal and perichondrial grafts, synthetic matrices, and growth
      factors: and other methods have the potential to stimulate the formation of a new
      articular surface. The long-term follow-up of small series of patients has shown
      that the transplantation of osteochondral autologous grafts and allografts can be
      effective for the treatment of focal defects of articular cartilage in selected
      patients. Thus far, none of these methods has been shown to predictably restore a
      durable articular surface to an osteoarthritic joint, and it is unlikely that any
      one of them will be uniformly successful. Rather, the available clinical and
      experimental evidence indicates that future optimum methods for the restoration
      of articular surfaces will begin with a detailed analysis of the structural and
      functional abnormalities of the involved joint and the patient's expectations for
      future use of the joint. On the basis of this analysis, the surgeon will develop
      a treatment plan that potentially combines correction of mechanical abnormalities
      (including malalignment, instability, and intra-articular causes of mechanical
      dysfunction), debridement that may or may not include hunted penetration of
      subchondral bone, and applications of growth factors of implants that may consist
      of a synthetic matrix that incorporates cells or growth factors or use of
      transplants followed by a postoperative course of controlled loading and motion.

PMID- 9571451
TI  - The treatment of isolated articular cartilage lesions in the young individual.
AB  - The treatment of isolated articular cartilage defects is an evolving field in
      orthopaedic surgery today. We have summarized the basic science and clinical date
      on the treatment of isolated articular cartilage defects. Further long-term
      controlled studies are required in order to compare definitively the efficacy of
      treatments in this difficult clinical area. In future studies,
      inclusion/exclusion criteria must be detailed, and classification systems need to
      be standardized Comparative analysis can then be performed to assess the efficacy
      of various techniques.

PMID- 9571452
TI  - Osteochondral allografts for reconstruction of articular defects of the knee.

PMID- 9571453
TI  - Bone grafting and new composite biosynthetic graft materials.

PMID- 9571454
TI  - A new method for reattachment of the tendo Achillis following retrocalcaneal
      exostectomy.
AB  - Currently there are a number of surgical techniques being utilized to address the
      entity of symptomatic, recalcitrant retrocalcaneal exostosis. This article
      presents a mechanical study of a modified surgical approach which has been
      developed at the Northern Virginia Podiatric Residency Program for the purposes
      of complete resection of all offending exostosis and calcifications, and
      maintenance of the anatomic configuration of the Achilles tendon with resultant
      asymptomatic function and cosmetic healing. The centerpiece of the surgical
      modification is the way in which the portion of reflected Achilles tendon is
      reattached to the calcaneus, utilizing soft-tissue anchors in combination with a
      modified Krackow suture technique. In order to delineate the relative strength of
      this suture technique, a cadaveric study was performed using six specimens. Each
      specimen underwent tendon repair with both a modified Krackow technique and a
      modified vertical mattress coaptation technique for a total of 12 studies. The
      force required to displace the tendon for distances of 0.5 cm and 1.0 cm was then
      recorded, and the data were statistically analyzed, with the modified Krackow
      technique proving to have a significantly better ability to resist distractive
      forces at both 0.5 cm (p = .01) and at 1.0 cm (p = .02) compared to the vertical
      mattress coaptation technique.

PMID- 9571455
TI  - Titanium anchors for the repair of distal Achilles tendon ruptures: preliminary
      report of a new surgical technique.
AB  - From January 1995 to July 1996, the authors used Mitek GIV titanium anchors to
      treat seven patients with acute rupture of the Achilles tendon (four men, three
      women; average age 52.42 years; range, 33-62 years). All subjects had a total
      rupture of the most distal aspect of the tendon; none had an avulsion fracture.
      After dissection down to the paratenon, the reinsertion site was selected and a 2
      to 3-cm-long trough carved through the cortex. Three holes were drilled at a
      distance of 0.5 cm one from the other and 1 cm parallel and distal to the trough.
      The anchors were then threaded, inserted into the holes, and engaged. Surgery was
      completed by resection of the frayed ends, reparation of the tendon, and
      insertion of the terminal end into the trough. At 6 months postoperative, a
      modified Mandelbaum and Pavanini clinical assessment indicated five excellent and
      two good outcomes. There were no cases of deep of superficial wound infection or
      skin necrosis. Despite the small number of patients and the short follow-up
      period, the authors believe this technique shows promise and that in selected
      cases the use of titanium anchors can facilitate the task of the surgeon and
      enable patients to return to normal and sports activities within 5 months after
      surgery.

PMID- 9571456
TI  - Flexor hallucis longus dysfunction.
AB  - Nineteen consecutive cases of flexor hallucis longus stenosing tenosynovitis that
      underwent operative tenolysis from September 1994 to December 1996 were
      retrospectively reviewed. This is classically a disorder of ballet dancers, and
      to a much lesser extent, running athletes. The patients were primarily
      nonathletic, male, and middle-aged. The mean symptom duration was 20 months,
      multiple physicians had been encountered, and misdiagnosis was common. Patients
      presented with overlapping signs and symptoms of flexor hallucis longus
      tendinitis, plantar fasciitis, and tarsal tunnel syndrome. A cross-reference of
      patients with posteromedial ankle pain, medial arch pain, and/or a positive
      Tinel's sign revealed that 14 (74%) and 6 (32%) feet had two of three, or all
      three signs, respectively. Magnetic resonance imaging and tenography proved
      valuable in establishing the correct primary diagnosis. Nonoperative protocols
      were unsuccessful. Flexor hallucis longus tenolysis was successful in each case
      with a mean return to regular activity at 9 weeks. Flexor hallucis longus
      stenosing tenosynovitis may be more prevalent than reported and should be a
      diagnosis of inclusion among all patient populations who present with posterior
      ankle, medial arch, and/or tarsal tunnel symptoms.

PMID- 9571457
TI  - Haglund's syndrome.
AB  - Haglund's syndrome is a painful condition of the heel caused by mechanically
      induced inflammation of the retrocalcaneal bursa, supracalcaneal bursa, and
      Achilles tendon. Surgical management has included calcaneal osteotomy, but
      results have been unpredictable because of the inability to measure accurately
      bone removal. A method was devised in this study to accurately determine
      radiographically the amount of bone removal necessary. Sixteen heels in 13
      patients underwent surgery after failing 21 months of conservative treatment. The
      desired osteotomy angle (preop x-rays) was compared to the actual angle obtained
      at surgery. A patient questionnaire, developed by the Outcome Study Committee of
      the AOFAS, was used to assess results. There were 13 good results and 3 failures.
      The average actual angle of the good results was 49 degrees and that of the poor
      results was 61 degrees. These results were statistically significant to a p =
      .0012. The average score obtained by the good results was 87 points, while that
      of the failures was 25 points. Follow-up was 42 months. The authors recommend
      that the osteotomy be made in such a way as to remove not only the superolateral
      deformity, but also to decompress the retrocalcaneal bursa and to remove the
      calcaneal step. In order to do so, an osteotomy angle of 49 degrees should be
      achieved.

PMID- 9571458
TI  - Modified Kidner procedure utilizing a Mitek bone anchor.
AB  - The recent development of small bone suture anchors has created several potential
      applications in reconstructive surgery of the foot. Mitek bone anchors are simple
      to insert, require less aggressive dissection and surgical time than reefing of
      the redundant posterior tibial tendon, and are a reliable method of tendon-to
      bone fixation. Mitek bone anchors are an excellent technique for the treatment of
      redundant tibialis posterior tendon following a modified Kidner procedure. In
      modified Kidner procedures involving an excessively large os tibiale externum,
      Mitek anchoring of the redundant tibialis posterior tendon to the navicular bone
      is an excellent means for secure plication of the posterior tibial tendon in
      cases involving intraoperative tendon laxity. A description of the Mitek Anchor
      System and technique of application in a modified Kinder procedure is presented.
      The purpose of this study was to describe patient satisfaction and long-term
      clinical outcomes of the modified Kinder procedure with and without the Mitek
      bone anchoring system. A retrospective study of the modified Kinder procedure was
      performed with 13 patients being evaluated, seven with Mitek anchoring and six
      without. The University of Maryland 100-point Painful Foot Center Scoring System
      was modified to be more specific to the modified Kinder procedure for assessment
      of subjective long-term results. Patient overall satisfaction was rated good to
      excellent by 85.6% of patients in the Mitek group and by 100% of patients in the
      non-Mitek group. Use of the Mitek anchor allowed for quicker postoperative
      recovery to resumption of ambulation without assistive devices (average of 3
      weeks vs. 4.42 weeks) and a quicker return to pain-free ambulation in normal
      shoegear (average of 4 weeks vs. 6 weeks). Mitek anchoring of the tibialis
      posterior tendon, theoretically, increases medial arch support as evidenced by
      14% of the Mitek group and 67% of the non-Mitek group requiring postoperative
      orthotics.

PMID- 9571459
TI  - Can synthetic bone models approximate the mechanical properties of cadaveric
      first metatarsal bone?
AB  - The authors evaluated the value of plastic foam models for approximating the
      mechanical properties of cadaveric bone. Three mechanical tests (3-point bending,
      cantilevered load to failure, screw push-out) were performed to evaluate the
      performance of fresh (nonpreserved) human metatarsals, plastic solid foam
      anatomic models, and modified anatomic models. The test results indicate that
      plastic models may simulate the mechanical properties of natural bone in tests in
      which only elastic deformation is achieved. However, under circumstances where
      load is applied until material failure, the mechanical properties vary
      dramatically. These tests indicate that specific goals should be established with
      these results in mind, when planning mechanical testing studies with either
      plastic or cadaveric models.

PMID- 9571460
TI  - Retrospective analysis of Silastic implant arthroplasty of the first
      metatarsophalangeal joint.
AB  - The purpose of this study was to evaluate the outcome of implant arthroplasty
      according to subjective, biomechanic, and radiographic parameters over a long
      period of time. Implants in 40 feet (27 patients) were analyzed at an average
      follow-up time of 8.25 years and a mean patient age of 63. The results were
      consistent with the subjective findings of previous studies that demonstrated
      that most patients were satisfied with the procedure. Ninety-six percent of the
      patients in this study confirmed they would undergo the procedure a second time.
      The radiographic results did not demonstrate a high incidence of implant fracture
      as previously reported. This review suggests that implants can be effective when
      used with patients who are carefully selected according to age, activity level,
      and diagnosis.

PMID- 9571461
TI  - Retrospective evaluation of postoperative intralesional steroid injections on
      wound healing.
AB  - Steroids have been implicated as an etiology in delayed wound healing. Although
      there is much documentation in the literature that steroids delay wound healing,
      most studies are in vitro or use high systemic doses. No studies have used a one
      time, postoperative, intralesional steroid injection and evaluated wound healing.
      This study retrospectively reviewed 73 patients with 115 foot and ankle surgeries
      over 12 years. Seventy-two patients had steroid injections and 43 did not. The
      average healing time for the steroid group was 17.1 +/- 10.5 days, and for the
      non-steroid group 17.3 +/- 8.75 days. There were two infections in the non
      steroid group, and one infection in the steroid group. There were five
      dehiscences in each group. The patients were further subdivided into groups based
      on age, gender, number of procedures, type of surgery, health status, steroid
      type, and steroid dose. The healing time increased in patients > 60 years old,
      and in immunocompromised patients. The patients who had more complex surgery had
      increased healing time. The males had a longer healing time than the females.
      Overall, there was not a statistically significant difference between the steroid
      groups and the non-steroid group. Therefore, one-time postoperative intralesional
      steroid injections were not found to delay wound healing.

PMID- 9571463
TI  - Laboratory considerations in the surgical treatment of acute hematogenous
      osteomyelitis of the calcaneus.
AB  - Surgical treatment of acute hematogenous osteomyelitis of the calcaneus is
      uncommon in the literature. Laboratory considerations to aid diagnosis as well as
      methods of diagnosis, surgical intervention, and management with a review of the
      literature are presented. A case of a 10-year-old female with acute hematogenous
      osteomyelitis of the calcaneus treated by surgical drainage, bone biopsy, and
      management with 12-month follow-up is discussed.

PMID- 9571462
TI  - Unusual case of postoperative infection caused by Morganella morganii.
AB  - Morganella morganii is a facultative Gram-negative anaerobe present in the human
      gastrointestinal system as normal flora. Clinically, the organism is important
      when it manifests as an opportunistic pathogenic infection elsewhere in the body.
      This paper reviews an unusual case in which M. morganii is the pathogen
      responsible for a devastating postoperative infection in a diabetic patient.
      Currently, there are no known reported cases in the literature of M. morganii as
      an etiologic pathogen for a postoperative foot infection. Prompt diagnosis and
      treatment of this organism is imperative to reduce the patient's overall
      morbidity and mortality.

PMID- 9571465
TI  - Recurrent osteochondroma.
AB  - Osteochondroma is the most common bone tumor of the foot. This should be easily
      recognized by foot and ankle specialists. Malignant transformation does occur,
      although it is quite rare, and should be a consideration when deciding on
      treatment. An unusual case of recurrent osteochondroma is reviewed.

PMID- 9571464
TI  - Nonunion of a Hawkin's group II talar neck fracture without avascular necrosis.
AB  - The authors present an unusual case of talar neck nonunion without avascular
      necrosis following a Hawkin's group II fracture. A review of the literature and
      treatment of this rare complication are discussed. The nonunion was treated by
      debridement and iliac crest bone grafting to the defect and external electrical
      bone stimulation. The deformity of the rearfoot caused by the fracture nonunion
      was addressed by using a triple arthrodesis utilizing the Synthes 7.3-mm
      cannulated screw system.

PMID- 9571466
TI  - Boxcar heel: an unusual etiology of hindfoot amputation requiring microvascular
      reconstruction.
AB  - A series of three subtotal plantar amputations arising from pedestrian versus
      railroad car trauma are presented. Microvascular muscle transplants allowed limb
      salvage. All patients are presently ambulating without assistance.

PMID- 9571467
TI  - Soft-tissue anchors.

PMID- 9571469
TI  - What is cold intolerance?
AB  - There are four types of symptoms on exposure to cold in the condition known as
      cold intolerance: pain/discomfort, stiffness, altered sensibility and colour
      change. They may occur in isolation or in any combination. Symptoms were present
      in at least 64% of 200 patients 24 months after hand injury. Pain was found to be
      the most troublesome symptom. Colour change in the digits was regarded by
      patients as the least troublesome symptom. Symptoms may begin immediately after
      injury, but are more likely to develop with the first onset of cold weather if
      there is a lag period between injury and onset. Pre-existing cold related
      symptoms are uniformly made worse by hand injury. A definition of the condition
      has been proposed and it has been suggested that this collection of symptoms be
      known as "Trauma Induced Cold Associated Symptoms".

PMID- 9571468
TI  - The role of cheilectomy in the treatment of hallux rigidus.

PMID- 9571470
TI  - An immunohistochemical study of palmar and plantar digital nerves.
AB  - We present a qualitative and semi-quantitative description of palmar and plantar
      digital nerves obtained from cadavers prepared for routine class dissection. The
      fingertips of the three most functionally important and sensitive digits, namely
      thumb, index and middle fingers, received more myelinated axons than those of the
      ring and little fingers. In both palmar and plantar nerves the numbers of myelin
      basic protein (MBP)-positive myelinated axons decreased proximodistally along
      each digit and also from thumb to little finger and hallux to little toe
      respectively. Our results suggest that there are up to ten times more myelinated
      axons in palmar digital nerves than in plantar nerves.

PMID- 9571472
TI  - Digital blocks with adrenaline. An old dogma refuted.
AB  - In the early part of the century, when adrenaline first became widely available,
      it was used in an uncontrolled manner and cases of ischaemic necrosis led to it
      falling into disfavour for hand surgery. Local anaesthesia with adrenaline is
      currently widely used for palmar and dorsal hand surgery but there remains a very
      deeply ingrained resistance to its use for digital anaesthesia. It is widely
      thought that it will cause irreversible digital artery vasospasm. This
      prospective study reports the effect of 2% lignocaine with 1:80,000 adrenaline
      digital blocks on various parameters of digital arterial blood flow in 100
      consecutive patients. Our findings show that adrenaline only temporarily reduced
      digital blood flow. Perfusion of the digits persisted in every case.

PMID- 9571471
TI  - Stimulated jitter measurement in the assessment of recovery after different
      methods of peripheral nerve repair.
AB  - The recording of stimulated jitter offers a quantitative method for following the
      recovery of neuromuscular function after peripheral nerve repair. In groups of
      rats, electrophysiological recording of jitter was carried out on control animals
      and on animals 90 days after sciatic nerve division and subsequent repair with
      either direct end-to-end suture (NS), nerve graft (NG) or freeze thawed muscle
      graft (FTMG). It was found that values for jitter were highest in the FTMG group.
      The NS and NG groups demonstrated statistically similar jitter values when
      compared with each other and with the normal. It was concluded that the speed of
      nerve regeneration is slower in the FTMG group, at least initially, and that 90
      days after sciatic nerve repair the FMTG group had an increase in the number of
      immature neuromuscular junctions when compared with the NS or NG groups. Jitter
      measurement would appear to offer a means of detecting small differences in nerve
      regeneration. The value of this in future developments in nerve repair is
      discussed.

PMID- 9571473
TI  - The natural history of post-traumatic reflex sympathetic dystrophy.
AB  - The paper presents the results of a prospective trial to examine the natural
      history of early reflex sympathetic dystrophy (RSD). Thirty patients with post
      traumatic RSD of the hand were observed without treatment. They were reassessed
      1, 2 and 6 months after diagnosis with a final assessment at 10 to 18 months
      (average 13 months). Twenty-seven patients completed the study. Three were
      withdrawn during the study because of persistence of signs and symptoms of RSD
      and were given further treatment. Of the 27 patients who completed the study,
      only one showed sufficient features of the condition to warrant the diagnosis of
      mild RSD. In the remaining 26, most features of RSD had resolved spontaneously.
      Pain and swelling disappeared more quickly than other features of RSD. Although
      the signs and symptoms of RSD had largely gone at 13 months, the hands were still
      functionally impaired because of weaker grip strength.

PMID- 9571474
TI  - A study of the dimensions and taper angles of the medullary canals of the
      proximal and middle phalanges.
AB  - The morphology and dimensions of the medullary canals of the proximal and middle
      phalanges have been studied with particular interest shown to the angle of taper
      of these canals. Measurements of 50 cadaveric fingers were taken from computer
      aided tomographic images using AutoCAD software. Tangents were fitted to the
      inner cortices in two orthogonal planes and the angles between them were
      measured. The angles of canal taper in the proximal phalanx were remarkably
      similar for each digit. This was also true for the middle phalanx of the index,
      middle and ring fingers but the taper of the middle phalanx of the little finger
      was found to be different.

PMID- 9571475
TI  - Ischaemia of the index finger and thumb secondary to thrombosis of the radial
      artery in the anatomical snuffbox.
AB  - We report on nine patients who presented with spontaneous ischaemia of the index
      finger and thumb over an 11 year period. Arteriography revealed thrombosis of the
      radial artery in the region of the anatomical snuffbox with evidence of digital
      artery embolization in each. None had suffered direct trauma to the area or had a
      demonstrable proximal source for thrombus. While the cause of radial artery
      thrombosis in our patients in not entirely clear, local inflammation and/or
      systemic disease may predispose to this entity.

PMID- 9571476
TI  - Conservative versus operative treatment for Kienbock's disease. A retrospective
      study.
AB  - In this retrospective study on Kienbock's disease, a comparison was made between
      21 cases operated on by various techniques and 22 cases treated conservatively,
      with a mean follow-up of 65 months. Operative management of the disease did not
      show any superiority over conservative treatment. Moreover, surgery was
      responsible for a loss of mobility of 24%, and for a change in social activities
      in about a quarter of the patients, while grip strength was only slightly
      improved. Surgical indications for Kienbock's disease should be carefully
      considered, keeping in mind their side-effects, and the relative benignity in
      some cases of the natural course of the disease.

PMID- 9571477
TI  - Flexor tendon repair using a stainless steel internal anchor. Biomechanical study
      on human cadaver tendons.
AB  - We have developed a stainless steel internal tendon anchor that is used to
      strengthen a tendon repair. This study tested its use in vitro to produce a
      repair that can withstand the tensile strength demands of early active flexion.
      Fresh human cadaver flexor digitorum profundus tendons were harvested, divided,
      and then repaired using four different techniques: Kessler, Becker or Savage
      stitches, or the internal tendon anchor. The internal splint repairs demonstrated
      a 99-270% increase in mean maximal linear tensile strength and a 49-240% increase
      in mean ultimate tensile strength over the other repairs. It is hoped that this
      newly developed internal anchor will provide a repair that will be strong enough
      to allow immediate active range of motion.

PMID- 9571478
TI  - A comparative study of two methods of controlled mobilization of flexor tendon
      repairs in zone 2.
AB  - This prospective study compares subjects following primary repair of flexor
      tendons in zone 2 using either controlled active motion or a modified Kleinert
      regime. A matched pairs design was employed, subjects being matched for gender,
      age and injury characteristics. Twenty-six pairs of subjects with 92 tendon
      injuries in 52 digits were assessed 12 weeks postoperatively in respect of range
      of motion and dehiscence. Outcomes were defined using the Strickland criteria. No
      statistically significant differences in respect of range of motion were
      demonstrated between the groups. Incidence of rupture, however, was significantly
      less in the modified Kleinert group (7.7%) than in the controlled active motion
      group (46%).

PMID- 9571479
TI  - The effect of the extent of A1 pulley release on the force required to flex the
      digits. A cadaver study on the thumb, middle and ring fingers.
AB  - The A1 pulley was released distally in consecutive stages by 25%, 50%, 75% and
      100% of its length. The force required to fully flex the digit at each stage was
      recorded. The force decreased with more extensive A1 pulley release and this
      became significant when more than 50% of the pulley was released. These changes
      were probably due to loss of friction force rather than bowstringing of the
      tendon.

PMID- 9571480
TI  - The effect of partial excision of the A2 and A4 pulleys on the biomechanics of
      finger flexion.
AB  - The purpose of this study was to investigate the effect of partial excision of
      the A2 and A4 pulleys on digital angular rotation and the energy required to flex
      the finger. Partial excision of A2 resulted in a statistically significant
      decrease in angular rotation of 3 and 5% after 50 and 75% excision, respectively.
      Partial excision of A4 failed to produce any significant differences in angular
      rotation. Combined partial excision of A2 and A4 resulted in a significant
      decrease of 5 and 8% after 50 and 75% excision, respectively. Significant
      differences in work of flexion occurred only after excision of 75% of the A2
      pulley. Although optimal finger function relies on the integrity of the A2 and A4
      pulleys which maintain the efficiency of the digital flexor system, these data
      suggest that 25% of the A2 pulley, up to 75% of the A4 and 25% of the A2 and A4
      together can be excised without significant effects on angular rotation.

PMID- 9571481
TI  - The motion analysis system and the fingertip motion area. Normal values in young
      adults.
AB  - The reliability of the motion analysis system and the normal value of the
      fingertip motion area have been studied in young adults. The results indicate
      that the motion analysis system is a reliable tool for the evaluation of
      fingertip motion. It was found that the fingertip motion area in young adults has
      a linear correlation with the square of the finger length. Therefore, the normal
      value of the fingertip motion area can be calculated from the finger length.

PMID- 9571482
TI  - The surgical management of the upper extremity anomalies associated with Du Pan
      syndrome.
AB  - Du Pan syndrome is a rare condition comprising complex brachydactyly with fibular
      hypoplasia that is inherited in an autosomal recessive manner. This article
      describes experience gained through the management of four patients with this
      disorder. The surgical management of the upper limb abnormalities is discussed
      and a detailed timetable for their treatment is suggested.

PMID- 9571483
TI  - Unilateral radioscaphoid synostosis with bilateral hypoplastic thumbs.
AB  - A fusion of the right radius and the scaphoid with ipsilateral hypoplasia of the
      thumb and hypoplasia of the left scaphoid and thumb is described in a 24-year-old
      man.

PMID- 9571484
TI  - Interpositional arthroplasty with Gore-Tex, Marlex or tendon for osteoarthritis
      of the trapeziometacarpal joint. A retrospective comparative study.
AB  - In this retrospective study of 26 patients with arthritis of the thumb
      carpometacarpal joint, we report the use of expanded polytetrafluoroethylene
      (ePTFE) (Gore-Tex) and polypropylene (Marlex) as interpositional materials for
      resection arthroplasty of the trapeziometacarpal joint. We have compared the
      results with those of "conventional" tendon interposition and those in the
      literature. In three patients the use of ePTFE (Gore-Tex) was complicated by
      marked clinical synovitis, resembling findings in silicone synovitis. Therefore,
      the use of ePTFE has been discontinued. Polypropylene seems to be a valuable
      alternative to tendon interposition arthroplasty.

PMID- 9571485
TI  - Thumb reconstruction by pollicization of an index finger stump combined with a
      wrap-around flap from the big toe.
AB  - A finger stump pollicization combined with a thin wrap-around procedure from the
      big toe for reconstruction of the thumb is described. This technique permits
      excellent functional and cosmetic restoration, providing length to the new thumb
      as well as widening the first web. There is joint motion in the reconstructed
      thumb. Sensibility of the transferred pulp is good and allows fine pinch without
      pulp shrinkage. This method is indicated in cases of multidigit amputations, for
      thumb loss near the carpometacarpal joint.

PMID- 9571486
TI  - Extended wrap-around flap for thumb reconstruction following radical excision of
      a congenital arteriovenous fistula.
AB  - A 38-year-old woman presented with a large congenital arteriovenous fistula in
      her left hand with ischaemic atrophy of the thumb and index finger. Radical
      resection of the lesion and ray amputation of the index finger was done. To allow
      radical excision and reconstruction of the thumb and skin defect, we used an
      extended wrap-around flap. This flap is useful for primary reconstruction of the
      thumb following radical excision of a congenital arteriovenous fistula involving
      the thumb.

PMID- 9571487
TI  - Carpal boss: destabilization of the third carpometacarpal joint after a wedge
      excision.
AB  - In a standard carpal boss procedure, the dorsal ligament of the involved
      carpometacarpal joint is cut in the process of performing a wedge excision. We
      studied the effect of such a dorsal ligament sectioning on the joint between the
      capitate and middle metacarpal bone in ten fresh-frozen wrist specimens. The
      passive range of motion of this joint was measured with the joint loaded into
      flexion and extension and in the unloaded neutral position. After the dorsal
      ligament of the carpometacarpal joint was cut, simulating a dorsal wedge
      excision, the passive range of motion was measured again. Analysis indicated that
      this simulated wedge excision approximately doubled the passive range of motion
      of the carpometacarpal joint. This study shows that such a procedure disturbs the
      normal anatomy and creates instability of the involved joint.

PMID- 9571488
TI  - Biomechanical properties of absorbable implants in finger fractures.
AB  - The mechanical rigidity of five different methods of pin fixation in two proximal
      phalangeal fracture models was studied and absorbable implants were compared with
      metallic implants in a biomechanical cadaver study. Thirty phalanges were tested
      in apex palmar bending, compression and torsion. Results showed that rigidity of
      absorbable implants was comparable with metallic implants, except in torsion.

PMID- 9571489
TI  - A cheap, disposable external fixator for comminuted phalangeal fractures.
AB  - Reduction of a severely comminuted fracture of a long bone in the hand can be
      difficult to hold. An external fixator can be the best method of maintaining
      satisfactory reduction in such fractures. A small, disposable external fixator is
      described, made from a syringe barrel and K-wires. It allows accurate reduction
      with minimal soft tissue trauma and is easy to construct and apply. It allows
      early mobilization of the digit and is inexpensive.

PMID- 9571490
TI  - Spontaneous healing of a non-union of the scaphoid.

PMID- 9571491
TI  - Solitary dislocation of the scaphoid. From case report to literature review.
AB  - Solitary dislocation of the scaphoid can be classified as simple, or complex if
      the distal carpal row is included. It may be total or partial. Partial
      dislocation of the proximal pole may occur in a radial, palmar or dorsal
      direction. Each type has a different significance in terms of surgical
      approaches, complications and prognosis.

PMID- 9571492
TI  - Simultaneous dislocation of the scaphoid and hamate bones.
AB  - We report a rare case of simultaneous dislocations of the hamate and scaphoid in
      an 18-year-old boy. Despite the extensive damage to the wrist joint, the
      functional results of open reduction and suture of intercarpal ligaments have
      been satisfactory, without carpal instability and degenerative osteoarthritis.

PMID- 9571494
TI  - Pregnancy-related carpal tunnel syndrome.
AB  - Clinical and electrophysiological features were studied in 52 cases of carpal
      tunnel syndrome (CTS) associated with 30 pregnancies. The duration of symptoms
      was less than 3 months before electrodiagnosis was performed. This study revealed
      a higher incidence of persistent, painful diurnal symptoms in pregnancy-related
      CTS (PRCTS) than in idiopathic CTS. PRCTS usually occurs for the first time (de
      novo) (24/30 cases), in primigravidas (15 cases) as well as multigravidas. The
      onset of symptoms was in the first or second trimester in 11 women, the third
      trimester in 12 women, or the post-partum period in seven women. Nerve conduction
      studies demonstrated evidence of an acute median nerve lesion at the wrist with
      motor and/or sensory conduction blocks in 20/30 women and severe denervation
      signs in five women.

PMID- 9571493
TI  - Hamate fracture with dislocation of the ring and little finger metacarpals.
AB  - We report a displaced body of hamate fracture in the coronal plane with
      dislocation of the ring and little metacarpals and interposition of these
      metacarpals between the two hamate fragments. The diagnosis, radiographic studies
      and the treatment of this unusual injury are discussed.

PMID- 9571495
TI  - Recurrent anterior interosseous nerve palsies related to pregnancy.
AB  - A rare association of anterior interosseous nerve palsy with pregnancy has been
      reported previously (Sood and Burke, 1997). We report further on this patient who
      has now experienced three separate anterior interosseous nerve palsies associated
      with pregnancies.

PMID- 9571496
TI  - Posterior interosseous nerve palsy.
AB  - Eleven patients with non-traumatic paralysis of posterior interosseous innervated
      muscles were divided into three types, and the association between the type of
      paralysis and sites of compression was investigated. Type 1 (drop finger and
      thumb) showed a simultaneous compression of the recurrent branch and the
      descending branch at the entrance point and within the supinator. Type 2 (drop
      fingers) had compression of the recurrent branch alone, and Type 3 (drop thumb)
      had compression of the descending branch alone. The exit point from the supinator
      is considered to be the site of compression in Types 2 and 3.

PMID- 9571498
TI  - Ulnar nerve laceration as a result of elbow arthroscopy.

PMID- 9571497
TI  - Intracapsular chondroma of the elbow producing a posterior interosseous nerve
      palsy.
AB  - We present a case report of a patient who presented with posterior interosseous
      nerve paralysis caused by an intracapsular chondroma arising within the elbow
      joint. We review the literature and discuss problems associated with making the
      diagnosis preoperatively.

PMID- 9571499
TI  - Median nerve contusion during endoscopic carpal tunnel release.
AB  - Median nerve contusion occurred in two patients treated by endoscopic carpal
      tunnel release. We discuss the possible cause of this complication and how to
      avoid it.

PMID- 9571500
TI  - Acute median nerve injury due to migration of a Kirschner wire.
AB  - Migration of orthopaedic implants such as K-wires is not unusual, but migration
      due to an improperly constructed brace has not been reported. This report
      describes such a mechanism in a case complicated by acute median nerve injury.

PMID- 9571501
TI  - von Willebrand's disease presenting as acute carpal tunnel syndrome.
AB  - We describe a patient who developed acute carpal tunnel syndrome due to
      spontaneous bleeding without a history of injury. Immediate decompression
      relieved the symptoms. Further haematological investigations revealed that the
      patient was suffering from von Willebrand's disease.

PMID- 9571502
TI  - Entrapment of the palmar cutaneous branch of the median nerve.

PMID- 9571503
TI  - Reversed palmaris longus muscle causing effort-related median nerve compression.
AB  - Two cases of effort-related distal median nerve compression in the dominant
      forearm caused by a reversed palmaris longus muscle are presented. Simple
      resection of the muscle belly was performed. Carpal tunnel release was done in
      one case, but in retrospect this was probably not necessary.

PMID- 9571504
TI  - Intraneural lipofibroma of the median nerve.
AB  - Intraneural lipofibroma of the median nerve is rare. We present three cases of
      this condition and discuss the surgical management. Open biopsy and carpal tunnel
      release are usually required.

PMID- 9571505
TI  - Intraneural ganglion of the branchial plexus.
AB  - We report a case of an intraneural ganglion of the brachial plexus. Excision
      relieved the symptoms.

PMID- 9571506
TI  - Attritional rupture of flexor tendons by the head of the ulna associated with a
      chronic longitudinal radioulnar dissociation.
AB  - A 62-year-old woman sustained multiple attritional ruptures of the flexor tendons
      at the wrist caused by displacement of the head of the ulna. She had had injuries
      of the wrist and elbow when she was young, which were thought to have caused
      chronic longitudinal radioulnar dissociation with palmar dislocation of the head
      of the ulna. Attrition of the flexor tendons by the dislocated ulnar head during
      pronation and supination was the major mechanism for the ruptures in this case.
      She was successfully treated with tendon transfer and resection of the ulnar
      head.

PMID- 9571507
TI  - Avulsion of the flexor digitorum profundus tendon associated with a chondroma of
      the distal phalanx.
AB  - An avulsion of the profundus tendon associated with a chondroma of the distal
      phalanx is presented. The injury occurred during housework and the tendon
      avulsion can be explained by a weakness of the profundus tendon insertion.

PMID- 9571508
TI  - Re-growth of a phalanx following removal for infection in a child.

PMID- 9571509
TI  - An unusual variant of the levator claviculae muscle encountered in exploration of
      the brachial plexus.
AB  - The levator claviculae muscle is a vestigal muscle which occurs in less than 2%
      of humans. The embryological origin of this muscle is controversial. We report a
      case in which an unusual variant of this muscle was encountered during
      exploratory surgery following a brachial plexus injury. The anatomical findings
      in this case suggest that this muscle may arise from either the
      sternocleidomastoid or trapezius muscles or from the primordial ventrolateral
      musculature.

PMID- 9571510
TI  - The effect of low frequency, long-wave ultrasound therapy on joint mobility and
      rehabilitation after wrist fracture.
AB  - Thirty-eight patients with dorsally-displaced distal fractures were prospectively
      studied to assess the clinical effects of low frequency ultrasound treatment,
      started immediately after plaster removal. Nineteen of the patients represented
      the control group and a double-blind protocol was followed. Assessment took place
      on the day of plaster removal and 2 and 8 weeks later. There was no significant
      difference in wrist motion and duration of follow-up between the treated and
      control patients.

PMID- 9571511
TI  - Efficacy of ultrasonic mass survey for abdominal cancer.
AB  - From August 1983 through March 1995, 204,099 people received ultrasonic mass
      survey of the abdomen for the first time. Among these examinees, 631 (0.31%)
      malignant neoplasm cases, such as 201 hepatocellular carcinoma (HCC), 81
      gallbladder (GB) cancer, 57 pancreatic cancer, and 169 renal cell carcinoma
      (RCC), were detected. Three hundred seventy six out of 590 cases (64%), excluding
      chronic leukemia cases and metastatic liver cancer cases, were surgically
      resected. The resection rate of HCC, GB cancer, pancreatic cancer, and RCC were
      25%, 88%, 49%, and 99%, respectively. The cumulative survival rate of the 376
      resected cases was 79.5% at 10 years. The cumulative survival rates of resected
      cases of HCC, GB cancer, pancreatic cancer and cumulative survival rates of
      resected cases of HCC, GB cancer, pancreatic cancer and RCC were 34% at ten
      years, 83% at 10 years, 49% at 7 years, and 99% at 10 years, respectively.
      Ultrasonic mass survey is dramatically useful for early detection of various
      kinds of abdominal cancers, especially RCC and GB cancer. From now on, many
      earlier abdominal cancers will be found by establishing and promoting ultrasonic
      mass survey systems.

PMID- 9571512
TI  - Effective medical examination of VDT workers using a new testing method of ocular
      alignment.
AB  - To investigate the relationship between asthenopia of VDT workers and the ocular
      alignment, we measured far and near alignment of 407 subjects (74 VDT workers
      with asthenopia, 137 VDT workers without asthenopia, and 196 non-VDT workers)
      using Total Vision tester (VT-500). There was no relationship between the
      asthenopia and the records of far alignment test. On the other hand, the
      incidence of exophoria and convergence insufficiency type in near alignment test
      was significantly high in the group of VDT workers with asthenopia. From these
      results, we speculate that cases who have exophoria or show incomplete fusional
      response measured under the near testing distance (50 cm) tend to complain of
      asthenopia.

PMID- 9571513
TI  - A study on home health care support information system for health evaluation.
AB  - The need for home health care has been increasing in Japan and the application of
      various techniques such as medical informatics are desired to support home health
      care services. Therefore, we developed an information system for health
      evaluation of the elderly including patients at home by applying multifunctional
      telephone set and an IC memory card, by which complaints, symptoms, and
      conditions by them can be collected, recorded, and transmitted to medical
      facilities. We also conducted an experiment for trial use of the system with the
      cooperation of elderly female volunteers. It was recognized that the elderly
      volunteers could operate the system with the help of public health nurses and
      their health information could be collected by the system. Although the developed
      system has some problems, it was suggested that the system would be useful for
      the support of health evaluation of elderly at home.

PMID- 9571514
TI  - Staged diabetes management: computerizing a disease state management program.
AB  - Recently, the Diabetes Control and Complication Trial (DCCT) and other similar
      studies have demonstrated that near-normalization of blood glucose in diabetes
      will reduce complications up to 75% but translation of these results into
      practice has been difficult. In an attempt to help provide the best possible
      control of patients with diabetes, we have produced an attempt to help provide
      the best possible control of patients with diabetes, we have produced a new
      disease state management system for diabetes, called "Staged Diabetes Management"
      (SDM), implemented it in over 100 sites worldwide, and developed a computer
      program to simplify its use. SDM, designed to change the way we deal with
      patients with diabetes, is based upon five principles: (1) community involvement
      in setting care guidelines; (2) negotiation of goals with patients; (3)
      appropriate timelines for therapeutic success; (4) use of flowcharts for medical
      decisions; and (5) evaluation of the program. SDM is designed to be altered by a
      community to meet its needs and resources. It encourages primary care physicians
      to deliver better diabetes care using a team approach and to refer patients with
      diabetes to specialists when appropriate. It has a complete set of materials for
      communities, individual health care providers and patients. SDM has been tested
      for changes in structure, process and outcomes. A meta-analysis of seven clinical
      trials with over 500 patients has shown a time-weighted average fall in
      hemoglobin A1c of 1.7 points (equivalent to a drop in mean blood glucose of about
      3.5 mM or 60 mg/dL). Preliminary pharmacoeconomic analysis demonstrates a
      lifetime cost saving of over $27,000 per patient. A computer program has been
      developed for the Microsoft Windows environment that contains a client-server
      database, based upon DiabCare, for the data file structure.

PMID- 9571515
TI  - Influence of smoking on serum carcinoembryonic antigen levels in subjects who
      underwent multiphasic health testing and services.
AB  - We quantified the effect of smoking on serum carcinoembryonic antigen (CEA)
      levels in 1341 subjects who underwent the multiphasic health testing and services
      in our center. Four hundred and sixty seven of them were smokers and the rest
      were nonsmokers. In males subjects, serum CEA levels were significantly higher in
      smokers (3.11 +/- 1.8 ng/ml) than in nonsmokers (2.14 +/- 1.8 ng/ml) (mean +/-
      SD; p < 0.01). For females, however, the levels had no significant differences
      between smokers (2.11 +/- 0.91 ng/ml) and nonsmokers (1.87 +2- 1.3 ng/ml). The
      CEA-positive subjects were 44, of whom 32 were male custom heavy smokers, and
      only 2 of them had gastrointestinal cancer. We concluded that the serum CEA level
      was influenced by smoking especially in males and its clinical significance for
      detection of carcinoma was doubtful.

PMID- 9571516
TI  - Automated telephone conversations to assess health behavior and deliver
      behavioral interventions.
AB  - The medical care system is not very effective in modifying health behavior of
      individuals, in particular, ensuring patient compliance with medication regimens,
      healthy diets, regular physical activity, and regular health screening, and in
      the avoidance of substance abuse. Telephone-Linked Care (TLC) is a
      telecommunications technology that enables computer-controlled telephone
      counseling with patients in their homes. It has been applied to the task of
      improving a number of different health behaviors. Randomized controlled studies
      suggest that use of the system for as little as 3 months is associated with
      improvement in adherence to medication regimens, dietary change in
      hypercholesterolemia, and increased physical activity among sedentary
      individuals. Future work involves applying the technology to other important
      health behaviors, optimally using health behavior theory in the system design,
      targeting use of TLC to the most appropriate patient groups, incorporating new
      computer and telecommunications technology into the system, and interfacing TLC
      into the health care delivery system.

PMID- 9571517
TI  - Consumer health information services: preliminary findings about who is using
      them.
AB  - Focus groups and in-depth telephone interviews were used to develop a telephone
      questionnaire later completed by people 55 years and older about their use of a
      Health Information Support Telephone Service (HISTS). Preliminary findings
      identified an equal number of well educated male and female callers, who called
      for information for themselves. The confidentially of the service was very
      important to respondents and may have impacted the time to recruit people for the
      focus groups. The second study described is a pilot test completed by three
      Consumer Health Information/Resource Centres (CHIRC). An Info Script was used by
      health professionals to direct people to information centres. Preliminary results
      indicate that over half of the participants stated they visited the information
      centre because they were given an Info Script and that they would not have gone
      without the Info Script.

PMID- 9571518
TI  - Study on management of examinees after multiphasic health check-ups.
AB  - Although the importance of follow-up and detailed examinations following the
      detection of abnormalities in thorough routine health checks is recognized
      extensively, marked interfacility variances are seen in the percentage of
      individuals advised to receive detailed examination, the percentage of
      individuals who actually receive the recommended detailed examination and the
      results of detailed examination. On the basis of the survey data collected by the
      Clinical Preventive Medicine Committee of the Japanese Association of Hospitals
      and the data collected during thorough routine health checks at our facility, we
      analyzed the percentage of individuals who were rated as requiring detailed
      examination and the percentage who actually received the recommended detailed
      examination, and found that these percentage varied greatly between different
      facilities. To minimize interfacility differences in these percentages; it seems
      necessary to review the criteria currently used for evaluation of health check
      data at individual facilities. To this end, we must discuss quantitative test
      data and data yielded by diagnostic imaging separately.

PMID- 9571519
TI  - Elevated serum hepatic aminotransferase in coking workers after exposure to coke
      oven emissions.

PMID- 9571520
TI  - Vitamin B6, vitamin C, and carpal tunnel syndrome.

PMID- 9571521
TI  - Absenteeism among employees who participated in a workplace influenza
      immunization program.
AB  - To assess the effectiveness of a free workplace immunization program at 3M's St.
      Paul, Minnesota locations, we examined the difference in sick leave hours taken
      from November 15, 1996, through March 15, 1997, for employees who had and did not
      have an influenza vaccination prior to the previous year's four-month influenza
      season (November 15, 1995-March 15, 1996). Among the 2,622 employees who self
      reported that they were not immunized in the previous year, there were, on
      average, 1.2 fewer hours of sick leave taken during the 1996-1997 influenza
      season than the comparable time period one year earlier (P < 0.05), although the
      exact reason for the absenteeism was not determined. In particular, we observed
      that female employees younger than 50 years of age with two or more children took
      3.1 hours less sick leave in the year they were immunized, compared with the
      preceding year (P < 0.0001). Among the 895 subjects who were immunized in both
      years, employees took 0.7 hours more sick leave during the 1996-1997 influenza
      season than the previous year (P = 0.46). Based on our findings, consideration
      should be given to workplace immunization programs. However, we urge caution in
      applying a "one-size fits all" approach to any cost-savings analysis from a
      company-sponsored immunization program because the workplace is not a homogeneous
      [corrected] environment, with regard to employees' age, gender, medical history,
      and home environment. All of these factors may directly or indirectly contribute
      to the risk of acquiring influenza and any of its complications.

PMID- 9571522
TI  - Work-related physical assault.
AB  - Violence in the workplace is a serious public health problem. Yet, to date,
      little has been documented relevant to non-fatal events associated with physical
      assault. The aim of the present study was to identify the magnitude of work
      related physical assault in Minnesota and to identify potential risk factors;
      both fatal and non-fatal cases were included. Minnesota workers' compensation
      records, relevant to assault, were used to identify 712 cases involving more than
      three days of lost work time for 1992; six homicide cases were included. Assault
      rates were calculated by industry and occupation. Women had an assault rate twice
      that of men (51 versus 26 per 100,000 workers). Workers in industries of social
      services (340), health services (202), and transportation (914) had the highest
      rates of assault per 100,000 full-time employees. The fact that in addition to
      overall workers' compensation costs of $1.6 million, the average lost time for
      closed compensated cases was 54 days (median, 14 days) and time to reach maximum
      medical improvement for 44% of the cases reporting was 156 days (median, 83
      days), indicates a major problem. The findings suggest that specific groups of
      workers are at risk for physical assault on the job. Further research is
      essential to identify specific risk factors that will enable the development of
      appropriate prevention strategies.

PMID- 9571523
TI  - What percentage of workers with work-related illnesses receive workers'
      compensation benefits?
AB  - This study estimates the rate at which workers suffering from occupational
      illnesses file for workers' compensation lost wage benefits and identifies some
      of the factors that affect the probability that a worker with an occupational
      illness will file. A database of reports of known or suspected cases of
      occupational illness is matched with workers' compensation claims data. Overall,
      between 9% and 45% of reported workers file for benefits. Data limitations
      prevent a more precise estimate of this rate, but a large proportion of workers
      with occupational illnesses clearly does not utilize the worker's compensation
      system. Logit analysis of a choice-based sample shows that women and employees of
      small firms are more likely than others to file for worker's compensation and
      that filing rates vary considerably across industries and diagnostic categories.
      Acute conditions related to the current job are no more likely to lead to claims
      than chronic conditions with long latency periods between exposure and
      development of disease.

PMID- 9571524
TI  - Parental occupation and childhood brain tumors: astroglial and primitive
      neuroectodermal tumors.
AB  - Data from a population-based case-control study in 19 counties in California and
      Washington State were used to investigate the association between parental
      employment and childhood brain tumors. Parents of 540 cases (including 308
      astroglial and 109 primitive neuroectodermal tumors) and 801 controls diagnosed
      from 1984 to 1991 were interviewed. Analysis was completed for parents' self
      reported industry of employment and job tasks during the five years preceding the
      birth of the child. Parents who worked in the chemical industry were at increased
      risk of having had children with astroglial tumors (fathers' odds ratio [OR] =
      2.1; 95% confidence interval [CI], 1.1-3.9); mothers' OR = 3.3; 95% CI, 1.4-7.7),
      but no trend by duration of employment was seen for mothers. Children of fathers
      employed as electrical workers were at increased risk of developing brain tumors
      of any histologic type (OR = 2.3; 95% CI, 1.3-4.0).

PMID- 9571525
TI  - Health care costs of worksite health promotion participants and non-participants.
AB  - Total and lifestyle-related medical care costs for employees of a major
      corporation participating in a worksite health promotion (WHP) program over a
      three-year period were compared with the costs for non-participants in a cross
      sectional study. The study population consisted of 8,334 active employees based
      in the Cincinnati headquarters of The Procter & Gamble Company. Adjusting for age
      and gender, participants (n = 3,993) had significantly lower health care costs
      (29% lower total and 36% lower lifestyle-related costs) when compared with non
      participants (n = 4,341) in the third year of the program. Similarly, in the
      third year of the program, participants had significantly lower inpatient costs,
      fewer hospital admissions, and fewer hospital days of care when compared with non
      participants. No significant differences in costs were found between participants
      and non-participants during the first two years of the WHP program. Conclusions
      drawn from this study are that long-term participation in a WHP that includes
      high-risk screening and intensive one-on-one counseling results in lower total
      and lifestyle-related health care costs, as well as lower utilization of hospital
      services.

PMID- 9571526
TI  - An examination of occupational fatalities involving impact-related head injuries
      in the construction industry.
AB  - Head injuries are the reason for which workers' compensation claims are most
      frequently filed and have the highest average cost per claim. The purpose of this
      study was to identify the construction industry trades with the greatest risk for
      an occupational fatality due to impact-related head injuries. Proportionate
      mortality ratios identified the highway and streets construction trades as having
      over three times the expected number of fatalities (P < 0.01) due to impact
      related head injuries than expected, while the heavy construction trades had over
      two times the expected number of fatalities (P < 0.01) due to impact-related head
      injuries. The majority of these fatalities were the result of vehicle incidents
      and the worker's being struck by various forms of equipment that were in the
      process of being moved. Prevention strategies should be focused on vehicle
      safety, driver education, safe material handling, and the use of hard hats.

PMID- 9571527
TI  - OCMAP-PLUS: a program for the comprehensive analysis of occupational cohort data.
AB  - The Occupational Cohort Mortality Analysis Program (OCMAP) has been redesigned
      for optimal microcomputer use and extended to include new computing algorithms.
      The new program, OCMAP-PLUS, offers a comprehensive, flexible, and efficient
      analysis of incidence or mortality rates and standardized measures in relation to
      multiple and diverse work history and exposure measures. New features include
      executable code, minimization of memory requirements, disk file storage of person
      day arrays, stratified analyses by geographic area, employment status and up to
      eight exposure variables, a data imputation algorithm for study members with
      unknown race, and enhanced algorithms for constructing several time-dependent
      exposure measures. New modules create grouped data files for Poisson and logistic
      regression and risk set files for use in relative risk regression analysis. The
      Mortality and Population Data System (MPDS) provides external comparison rates
      and proportional mortalities. Analysis from two recent cohort mortality studies
      illustrate several new features.

PMID- 9571528
TI  - Case-control study of idiopathic pulmonary fibrosis and environmental exposures.
AB  - The authors conducted a matched case-control study of interstitial lung disease
      (ILD) using a self-administered questionnaire. All cases in the practice of two
      pulmonary specialists were identified. Cases were excluded if they were thought
      to have occupational exposures as a contributor, hypersensitivity pneumonitis or
      sarcoidosis, or some other well-recognized cause. Three controls were matched by
      sex and age (one year) as identified through orthopedic surgeons at the same
      institutions. Two rounds of a questionnaire were mailed; 17 cases (37.7%) and 94
      controls (32.4%) responded to the questionnaire, although many of the case
      addresses were no longer valid. Individuals with ILD were 16.0 times as likely to
      report mold exposure and 11.1 times as likely to report silica as were controls
      in their workplace. Odds ratios associating ILD with moisture indicators in the
      home were in the same range as previously published associations between such
      indicators and wheezing. ILD may have environmental and occupational causes that
      warrant more systematic exploration.

PMID- 9571529
TI  - Characteristics of the healthy worker effect: a comparison of male and female
      occupational cohorts.
AB  - The healthy worker effect (HWE) poses a serious methodological problem to
      investigators of occupational cohorts in that it may mask mortality excesses that
      result from occupational exposures. This problem is further complicated by the
      fact that the strength of the HWE generally varies according to sociodemographic,
      employment, and time-related factors. While the HWE has been well documented
      among numerous cohorts of male workers, little is known about its expression
      among female occupational workers. Follow-up mortality data on 44,154 employees
      from the Hanford nuclear facility for the period of 1944-1986 were examined using
      standardized mortality ratio (SMR) analysis to assess whether modifiers of the
      HWE were expressed differently in females than in males. Results of this analysis
      show that while the HWE was modified by race, age at hire, occupational class,
      and length of follow-up in both male and female cohorts, different patterns of
      modification emerged across the two subgroups. Learning about how gender
      differentiates expression of the HWE will help investigators more precisely
      assess the confounding effect of the HWE in studies of working cohorts.
      Therefore, this study's findings are relevant for designing and interpreting
      future occupational cohort studies.

PMID- 9571530
TI  - Statistical approaches to determine analytical variability and specifications:
      application of experimental design and variance component analysis.
AB  - Assessment of analytical variability is recognized as an important factor for the
      establishment of specifications. Estimation of the variance for an analytical
      procedure can be accomplished using a variety of approaches. The approach of
      variance component analysis was applied retrospectively, as well as
      prospectively, to estimate analytical variance. The prospective approach also
      included the use of experimental design. Recent new drug substance examples
      illustrating these approaches are presented. In these examples, the analytical
      property of potency was evaluated. Factors examined in the experimental design
      include laboratory, day, analyst, instrument and column. Process variability can
      also be determined by variance component analysis. For a stable drug substance,
      combining the analytical and process variances provides an estimate on the total
      variance for the analytical property of potency. With the total variability
      statistically derived, an appropriate specification that is consistent with
      process and analytical capability can be established.

PMID- 9571531
TI  - Monitoring oxygen partial pressure in tissue using microdialysis sampling and
      membrane coated oxygen sensors.
AB  - The use of microdialysis sampling coupled to oxygen sensors for monitoring oxygen
      tension in the tissue of animals was examined. The response time of the
      microdialysis sampling system was not different than oxygen sensors implanted
      directly in the tissue. The microdialysis system could be calibrated in vivo
      using the no-net-flux calibration method while directly implanted oxygen sensors
      had to rely on in vitro calibration. No difference was found in the oxygen
      tensions determined in vivo between microdialysis sampling and direct sensor
      implantations.

PMID- 9571532
TI  - Determination of PNU 153429, a new polysulphonated derivative of distamycin A, in
      rat plasma by reversed-phase ion-pair high-performance liquid chromatography with
      ultraviolet detection.
AB  - A rapid and selective ion-pair high-performance liquid chromatographic (HPLC)
      method for the determination of 2,2'-(carbonylbis(imino-N-methyl-4,2-pyrrole
      carbonylimino (N-methyl-4,2-pyrrole)carbonylimino)) -bis(1,5
      naphtalenedisulphonic acid), tetrasodium salt (PNU 153429,I) in rat plasma has
      been developed. I is a new drug currently under investigation for the treatment
      of rheumatoid arthritis. Aliquots of 100 microliters of plasma spiked with 10
      microliters of internal standard solution (PNU 145156E, I.S.) were added to 100
      microliters of acetonitrile and vortex mixed. After centrifugation, diluted
      aliquots of the supernatant were transferred to autosampler vials and analyzed by
      reversed-phase ion-pair liquid chromatography under isocratic conditions. The
      retention times of I.S. and I were approximately equal to 8 and 12 min,
      respectively. Quantitation was achieved by ultraviolet detection at 323 nm. The
      assay had a limit of quantitation of 0.1 micrograms ml-1 when 100 microliters of
      plasma were analyzed. The linearity, precision and accuracy of the method were
      evaluated. No interference from blank rat, mouse, dog, monkey and human plasma
      was observed. The suitability of the method for in vivo samples was checked by
      analysis of plasma samples drawn from three cannulated male rats that had
      received a single 100 mg kg-1 i.v. dose of the test compound.

PMID- 9571533
TI  - Automated on-line dialysis for sample preparation and HPLC analysis of
      antidepressant drugs in human plasma. Inhibition of interaction with the dialysis
      membrane.
AB  - Antidepressant drugs interact with the dialysis membrane and were selected as
      model substances to study inhibition of analyte-membrane interactions. A
      chemometric approach based on response surface modelling was used for screening
      and optimisation of dialysis recoveries. Optimal dialysis recoveries (52-65%)
      were obtained for the model compounds (mianserine, amitriptyline, nortriptyline,
      imipramine and desimipramine) when a cationic surfactant added to the donor
      solution of the dialyser was used to inhibit analyte-membrane interactions.
      Automated analysis of antidepressants in plasma was performed by connecting the
      ASTED (Automated Sequential Trace Enrichment of Dialysates) system to high
      performance liquid chromatography (HPLC). The drugs were detected by ultraviolet
      detection and fluorescence detection after post-column photochemical reaction.
      Validation of the method showed linear standard curves for all the drugs in the
      concentration range 50-2000 nmol 1-1. Within-and between day relative standard
      deviations ranged from 1.1 to 5.7%.

PMID- 9571534
TI  - Development and application of sensitive HPLC assays for NK3 antagonists in rat
      plasma.
AB  - CAM 5500 and CAM 5187 are new nonpeptide tachykinin NK3 receptor antagonists with
      different lipophilicity and solubility. We have developed and validated two
      separate, simple HPLC methods for quantitation of these two compounds in plasma
      to support oral pharmacokinetic/bioavailability studies in rats. The two
      compounds in plasma were extracted on cyano SPE cartridges with different washing
      schemes to optimize extraction efficiency and chromatographic specificity. The
      analytes and internal standard in the resulting extracts were chromatographed on
      a C18 HPLC column, using mobile phases containing different phosphate buffer
      strengths and acetonitrile concentrations. Both compounds were detected using UV,
      Peak area ratios were proportional over the concentration range of 50-3000 ng ml
      1 for CAM 5500, and 100-1500 ng ml-1 for CAM 5187. Stability profiles of both
      drugs and internal standard in rat plasma at 37 degrees C and in injection
      solvent at ambient temperature were good. Assay precision, based on quality
      controls, was < 5.6% and 13.4% (%RSD) for CAM 5500 and CAM 5187, respectively.
      Similarly, assay accuracy for both compounds was within +/- 7.1% and +/- 6.0%
      (%RE), respectively. The HPLC methods were successfully applied to assay samples
      from two oral bioavailability studies. Oral bioavailability studies were
      conducted for each compound in rats receiving a PO dose of 20 mg kg-1 or an i.v.
      dose of 5 mg kg-1. Despite their difference in lipophilicity and solubility, the
      absolute oral bioavailability of CAM 5500 (5.3 +/- 4.8%) is similar to that of
      CAM 5187 (8.8% +/-3.2%).

PMID- 9571535
TI  - Application of solid-phase extraction in the method development for determination
      of SEPA, an acronym for soft enhancement of percutaneous absorption, in human,
      rat, and rabbit serum using GC-FID method.
AB  - A new nonaqueous topical minoxidil formulation containing SEPA (2-n-nonyl-1,3
      dioxolane) for enhancement of percutaneous absorption was under evaluation. SEPA
      does not have chromophore for either ultraviolet or fluorescence detection using
      liquid chromatography and has no functional groups for derivatization. Therefore,
      a direct gas-chromatographic method with flame-ionization detection (GC-FID) was
      developed. Owing to the limited detection response of the FID detection, it needs
      a selective and concentrated extract for GC-FID analysis to improve the assay
      sensitivity to meet the requirement for pharmacokinetic evaluation after topical
      application. In addition, SEPA is a very volatile compound. Any extraction
      procedures involving evaporation will result in a poor recovery. The application
      of solid-phase extraction (SPE) makes it possible to achieve a selective and a 10
      fold concentrated extract with an absolute extraction recovery of approximately
      90%, which greatly improved the assay sensitivity. This method involved the
      extraction of SEPA and the internal standard (2-n-heptyl-1,3-dioxolane) from
      serum (0.1-1 ml) with 100 microliter of hexane-chloroform (1:1, v:v) using a 50
      mg 1.0 ml-1 phenyl SPE column (Varian, Harbor City, CA, USA), followed by direct
      GC-FID analysis on a fused-silica column chemically bonded with cross-linked
      methyl silicone gum phase (Hewlett Packard Ultra-1, 12 m x 0.2 mm x 0.33 micron,
      Avondale, PA, USA). The assay demonstrated a lower limit of quantitation of 2.5
      ng ml-1 and a linear range of 2.5 to 250 ng ml-1 with intra- and inter-assay
      precision and accuracy of < or = 10%.

PMID- 9571537
TI  - Quantitative analysis of HBY 097 and its metabolites in human serum and urine by
      HPLC.
AB  - Two HPLC methods were developed: one for the quantitation of HBY 097 reverse
      transcriptase inhibitor and its metabolites M2 and M3 in human serum, and one for
      the quantitation of metabolite M5 in urine. The HPLC procedure for the
      quantitation of HBY 097 and its metabolites M2 and M3 in human serum involved
      protein precipitation with acetonitrile followed by automated on-line trace
      enrichment. The HPLC procedure for the analysis of metabolite M5 in urine
      involved enzymatic hydrolysis of urine with beta-glucuronidase to convert
      metabolite M5 (glucuronide of M3) to M3. Reverse phase chromatographic separation
      with gradient elution. UV detection at 335 nm, and internal standard were used to
      quantitate analytes in both procedures. The lower quantitation limits were 25 ng
      ml-1 for HBY 097 and metabolites M2 and M3 in serum, and 0.5 microgram ml-1 for
      the metabolite M5 in urine measured as metabolite M3 after hydrolysis. The HBY
      097 and metabolite M3 concentrations were specific but metabolite M2 was semi
      specific because the two diastereomers of M2 were not resolved by the present
      chromatographic procedure. Both procedures were applied to the quantitation of
      HBY 097 and its metabolites in serum and urine of HIV positive patients who were
      enrolled in a clinical study of drug safety and pharmacokinetics.

PMID- 9571536
TI  - HPTLC analysis of sphingomylein, ceramide and sphingosine in ischemic/reperfused
      rat heart.
AB  - Since the sphingomylein-ceramide-sphingosine pathway, especially ceramide, has
      been shown to induce programmed cell death (apoptosis), and since apoptosis may
      be involved with ischemic/reperfused injury in the heart, it became desirable to
      quantitate the three components in ischemic/reperfused rat heart. One group of
      rat hearts (n = 6) was isolated and perfused with Krebs-Henseleit buffer using
      the Langendorff non-recirculating mode. The hearts were perfused for 10 min, made
      ischemic for 30 min and reperfused for 120 min. Hearts were collected and stored
      at - 70 degrees C before ischemia, after ischemia and after 30, 60 and 120 min of
      reperfusion. The hearts were homogenized, and lipids were extracted using the
      Folch method. The lipids were then chromatographed on Whatman silica gel 60 A
      high-performance thin-layered chromatography (HPTLC) plates. The plates were
      developed with iodine, photographed using Photoshop software and quantitated
      using NIH Imaging software. The results show a 50% decrease of sphingomylein
      during reperfusion with a corresponding increase in ceramide with sphingosine
      showing a smaller decrease as compared with the ceramide increase.

PMID- 9571538
TI  - Chiral bioanalysis of warfarin using microbore LC with peak compression.

PMID- 9571539
TI  - The electroanalysis of mannitol, xylose and lactulose at copper electrodes:
      voltammetric studies and bioanalysis in human urine by means of HPLC with
      electrochemical detection.
AB  - The electrochemical behavior of mannitol, xylose and lactulose has been
      investigated at a copper working electrode. A sensitive, accurate and precise
      method employing HPLC with electrochemical detection in the d.c. amperometric
      mode, has been developed and validated for the determination of mannitol and
      lactulose in human urine. The ratio of these probe carbohydrates is altered in
      conditions that cause damage to the intestinal mucosal barrier. Systematic
      studies employing cyclic voltammetry indicate that the electrode reaction
      involves an electrocatalytic oxidation of each carbohydrate in a process yielding
      a single irreversible anodic wave that is dependent on the ionic strength of the
      sodium hydroxide supporting electrolyte solution. High performance liquid
      chromatography with electrochemical detection was performed using a thin-layer
      cell housing a custom manufactured copper working electrode. The optimized HPLC
      method can detect 72, 57 and 419 pg of mannitol, xylose and lactulose injected on
      column, respectively. The corresponding linear calibration ranges are 359 pg-2.24
      microgram, 57.4 pg-896 ng and 419 pg-262 ng, respectively. Solid-phase extraction
      of human urine on polar sorbents, and direct injection after simple 1 + 99
      dilution in 0.025 M NaOH were compared for bioanalysis. Direct injection was
      selected for further method developed as the technique proved robust and simple.
      The optimized method was validated for the determination of mannitol and
      lactulose in human urine over the concentration ranges predicted when assessing
      intestinal permeability (0.25-2.5 mg ml-1 mannitol and 0.05-1.0 mg ml-1
      lactulose). Over these ranges intra- and inter-assay bias is < +/- 6.5%, and
      imprecision (coefficient of variation) is < 9% for each carbohydrate. The
      validated method provides a useful alternative to HPLC with pulsed-amperometric
      detection at gold electrodes.

PMID- 9571540
TI  - Chiral high performance liquid chromatography resolution of ibuprofen esters.
AB  - Two cellulose-based chiral stationary phases (Chiralcel OD and Chiralcel OJ) were
      compared on their ability to resolve various aliphatic ibuprofen esters.
      Chiralcel OJ with hexane as the mobile phase allows for the separation of most of
      the esters. Observed changes in resolution depending on the solute nature
      (basicity of the solute, esterified alcohol chain length, presence of a double
      bond) are discussed. An example of the application of this method for following
      the kinetic resolution of racemic ibuprofen is presented.

PMID- 9571541
TI  - Simultaneous determination of phenytoin, carbamazepine, and 10,11-carbamazepine
      epoxide in human plasma by high-performance liquid chromatography with
      ultraviolet detection.
AB  - The Bioanalytical Chemistry Department at the Madison facility of Covance
      Laboratories, has developed and validated a simple and sensitive method for the
      simultaneous determination of phenytoin (PHT), carbamazepine (CBZ) and 10,11
      carbamazepine epoxide (CBZ-E) in human plasma by high-performance liquid
      chromatography with 10,11 dihydrocarbamazepine as the internal standard.
      Acetonitrile was added to plasma samples containing PHT, CBZ and CBZ-E to
      precipitate the plasma proteins. After centrifugation, the acetonitrile
      supernatant was transferred to a clean tube and evaporated under N2. The dried
      sample extract was reconstituted in 0.4 ml of mobile phase and injected for
      analysis by high-performance liquid chromatography. Separation was achieved on a
      Spherisorb ODS2 analytical column with a mobile phase of 18:18:70
      acetonitrile:methanol:potassium phosphate buffer. Detection was at 210 nm using
      an ultraviolet detector. The mean retention times of CBZ-E, PHT and CBZ were 5.8,
      9.9 and 11.8 min, respectively. Peak height ratios were fit to a least squares
      linear regression algorithm with a 1/(concentration)2 weighting. The method
      produces acceptable linearity, precision and accuracy to a minimum concentration
      of 0.050 micrograms ml-1 in human plasma. It is also simple and convenient, with
      no observable matrix interferences.

PMID- 9571543
TI  - Choice of capillary electrophoresis systems for the impurity profiling of drugs.
AB  - In order to develop a strategy for the impurity profiling of drugs, the
      possibilities of some capillary electrophoresis systems were investigated. A
      mixture containing a drug and some of its possible impurities has been used as a
      model problem. The test compounds were investigated by capillary zone
      electrophoresis (CZE) and by micellar electrokinetic chromatography (MEKC). The
      pH of the CZE buffer was varied, but the two stereoisomers could not be
      separated. Moreover, CZE is not suitable for neutral compounds. In MEKC, two
      different types of surfactants, sodium dodecyl sulphate (SDS) and
      cetyltrimethylammonium bromide (CTAB), have been used and the effect of type and
      concentration modifier on the separation and the elution window was studied. In
      the SDS system, both the resolution and the elution window could be increased
      considerably by the addition of modifier. The use of two MEKC systems of
      different selectivity seems to be a combination with high potential for the
      impurity profiling of drugs.

PMID- 9571542
TI  - HPLC determination of cisatracurium besylate and propofol mixtures with LC-MS
      identification of degradation products.
AB  - A stability-indicating HPLC method was developed to simultaneously determine
      cisatracurium besylate and propofol in mixtures. The effects of organic modifier,
      ionic strength and the pH of the mobile phase on resolution and retention were
      investigated. A baseline separation was achieved on an octadecylsilane column
      with an isocratic mobile phase of acetonitrile-ammonium formate (pH 5.2; 0.3 M)
      (50:50, v/v). Cisatracurium and propofol were confirmed by both retention time
      and mass-to-charge ratio using LC-MS. The degradation products of cistracurium
      were identified by ESI positive-ion detection as Hofmann elimination and ester
      hydrolysis products of cisatracurium. There were no propofol degradation products
      observed. The quantitation of the two drugs was accomplished using UV detection
      at 280 nm. This method showed linearity for cisatracurium besylate and propofol
      in the 9-128 and 37-592 micrograms ml-1 ranges, respectively. Accuracy and
      precision were in the 0.4-1.4 and 0.4-2.9% ranges respectively, for both
      analytes.

PMID- 9571544
TI  - Improving ion-trap GC-MS quantitation limits for therapeutic agents extracted
      from rat plasma.
AB  - Insufficient quantitation limits using ion-trap gas-chromatography mass
      spectrometry (GC-MS) prevented the assay of some samples during a preliminary
      screening of preclinical rat plasma samples (50 microliter) containing novel,
      polar therapeutic agents. Few options were available for improving the lower
      limit of quantitation. The limited amount of sample available precluded the
      extraction additional plasma. Lipid-liquid extraction recoveries were greater
      than 90% throughout the range of the standard curve (500-2000 ng ml-1).
      Chromatography was optimized and multiple, equivalent sites for analyte
      fragmentation were precluded, using MS-MS to improve assay sensitivity.
      Quantitation limits were decreased 10-fold however, by using a larger syringe to
      increase the injection volume from 5 to 50 microliter, in combination with a
      universal programmable injector. These large injection volumes required changes
      in the injector events program and in column plumbing. Additionally, evaluation
      of injection liner packing material demonstrated a 2-fold improvement in
      sensitivity, using carbofrit, relative to silanized glass wool. Converting to
      inert ion-trap electrodes did not appear to affect the detection limit, perhaps
      due to over-riding peak broadening during gas chromatography. The changes
      described produced a 20-fold improvement in the lower limit quantitation.

PMID- 9571545
TI  - Third Annual Nidek International Excimer Laser User's meeting. Phuket, Thailand.
      December 6-8, 1997. Proceedings and abstracts.

PMID- 9571546
TI  - Laser in situ keratomileusis for simple myopic, mixed, and simple hyperopic
      astigmatism.
AB  - PURPOSE: To summarize initial results of astigmatic laser in situ keratomileusis
      (LASIK) for 41 eyes of 26 patients using the EC-5000 Nidek system and assess its
      safety, efficacy and predictability. METHODS: The EC-5000 Nidek excimer laser was
      used to correct simple myopic, mixed, and simple hyperopic astigmatism with
      manifest cylinder from 2.00 to 6.50 D. Ablation zone diameters were 6.5 mm (steep
      meridian ablation) to 7.5 mm (flat meridian ablation) with a repetition rate of
      40-41 Hz. In eyes with simple myopic and mixed astigmatism, ablation was
      performed in both meridians; in eyes with simple hyperopic astigmatism, ablation
      was performed in the flat meridian alone. Follow-up was 3 months in all eyes.
      RESULTS: Uncorrected visual acuity was 20/40 or better in 85% of the eyes.
      Uncorrected visual acuity was equal to the preoperative spectacle-corrected
      visual acuity in 63% of the eyes. Intended cylinder correction was within 1.00 D
      in 95% of eyes. No eyes lost lines of spectacle-corrected visual acuity.
      CONCLUSION: LASIK using the EC-5000 excimer laser appears to effective in the
      treatment of simple myopic, mixed, and simple hyperopic astigmatism, with
      favorable results as compared to those previously described for astigmatic
      keratotomy.

PMID- 9571547
TI  - Laser in situ keratomileusis for myopia.
AB  - PURPOSE: To evaluate the efficacy of laser in situ keratomileusis (LASIK) for
      myopia. METHODS: We performed LASIK on 55 eyes using the Nidek ED-5000 excimer
      laser. We altered the PRK algorithms to make them appropriate for LASIK. The
      Chiron automated corneal shaper was used to create the flap. RESULTS: A high rate
      of satisfaction was noted among patients and the complication rate was low. Our
      retreatment rate was 6%. CONCLUSION: Our algorithms for myopic LASIK ablations
      using the Nidek EC-5000 are accurate.

PMID- 9571549
TI  - Long-term results of photorefractive keratectomy for hyperopia and hyperopic
      astigmatism.
AB  - PURPOSE: This study was conducted to determine the safety and efficacy of using
      the Nidek EC-5000 excimer laser for photorefractive keratectomy to correct
      hyperopia and hyperopic astigmatism. METHODS: We treated 67 eyes of 44 patients
      for hyperopia and hyperopic astigmatism with the Nidek EC-5000 excimer laser. The
      algorithm provided an ablation zone of 5.5 mm diameter with the addition of a
      tapered transition zone of 3.5 mm diameter, for a total ablation of 9 mm
      diameter. RESULTS: Uncorrected visual acuity (geometrical mean) changed from 0.16
      to 0.37 at 12 months; corrected visual acuity (geometrical mean) changed from 0.8
      to 0.89; mean sphere decreased by 2.08 D from 3.76 to 1.40 D (range, 1.70 to 1.68
      D) and cylinder by 1.40 D from 2.20 to 1.00 D. Refractive results for < or = 3.00
      D were reasonably accurate and stable, but for > +3.00 D, undercorrection and
      regression over l year were the rule. CONCLUSION: Hyperopic PRK proved to be a
      safe technique in regard to the risk of loss of visual acuity with no central
      corneal opacities and with a generally rapid recovery of baseline spectacle
      corrected visual acuity, but the predictability of correction greater than +3.00
      needs improvement.

PMID- 9571548
TI  - Laser in situ keratomileusis for hyperopia and hyperopic astigmatism.
AB  - BACKGROUND: The correction of hyperopia by excimer laser remains challenging
      because the procedure is followed by regression and loss of effect. We evaluated
      excimer laser in situ keratomileusis (LASIK) to correct hyperopia and hyperopic
      astigmatism using the NIDEK scanning slit excimer laser and a modified nomogram.
      METHODS: The study included the first consecutive 58 eyes treated for hyperopia
      and hyperopic astigmatism by one surgeon. All eyes were operated at the
      Alexandria Eye Center, Alexandria, Egypt using the Nidek excimer laser and the
      Chiron automated corneal shaper. Astigmatic correction was done first by myopic
      ablation using a 5.0 mm ablation zone and a 5.5 mm transition zone, followed by
      narrow hyperopic ablation using a 5.5 to 7.5 mm zone. RESULTS: Mean preoperative
      cycloplegic spherical equivalent refraction was +3.75 D (range, +1.00 to +6.00
      D). Mean preoperative astigmatism was 2.75 D (range 0 to 4.00 D). After hyperopic
      LASIK, all eyes had a reduction in their hyperopia, but regression occurred
      gradually until the last follow-up examination. At 6 months follow-up, the mean
      cycloplegic refraction was +2.25 D (range, 0 to +3.25 D). The postoperative
      astigmatism had a mean of 1.25 D (range 0 to 2.75 D). Four eyes had a reduction
      in the quality of vision due to a decentered ablation and a small ablation zone,
      but no other vision threatening complications were reported. CONCLUSION: LASIK to
      correct hyperopia and hyperopic astigmatism is safe, effective, and repeatable.
      Predictability and long-term stability needs improvement. A better ablation
      profile and modified algorithm need to be provided by excimer laser
      manufacturers.

PMID- 9571550
TI  - A scanning and rotating slit arF excimer laser delivery system for refractive
      surgery.
AB  - PURPOSE: This study was designed to investigate the quality of a scanning and
      rotating slit delivery system of an ArF excimer laser (Nidek EC-5000). METHODS:
      The ablation patterns on polymethylmethacrylate (PMMA) wafers were examined by
      scanning electron microscopy. The influence of inhomogeneities in the beam
      profile was simulated on a computer and compared with a conventional large-area
      ablation system. The impairment of the ablation rate by radiation absorption of
      the ablation plume was measured as a function of the repetition rate and the
      application of a fixation ring. RESULTS: The scanning and rotating slit delivery
      system is tolerant of small-beam non-homogeneities. The ablation rate is
      sensitive to the dynamics of the ablation plume. CONCLUSIONS: Although the
      operating procedure takes less time with a large-area ablation system, a scanning
      and rotating delivery system has the advantage of reliable and homogeneous
      removal of corneal tissue.

PMID- 9571551
TI  - Evaluation of hyperopic photoablation profiles.

PMID- 9571552
TI  - Retreatment of regression after photorefractive keratectomy for myopia.
AB  - PURPOSE: To study results of retreatment after regression in myopic patients who
      underwent photorefractive keratectomy (PRK). METHODS: Procedures were performed
      with the Nidek EC-5000 excimer laser. This was a retrospective study of 20 of
      2127 patients, with follow-up of at least 6 months, who underwent repeated
      excimer laser ablation. RESULTS: No patient with low myopia had regression. We
      evaluated six eyes (group I) with moderate myopia; 13 eyes (group II) with high
      myopia; and ten eyes (group III) with extreme myopia. Average uncorrected visual
      acuity at 6 months after retreatment was 0.73 +/- 0.21 in group I, 0.64 +/- 0.35
      in group II, and 0.61 +/- 0.38 in group III. At six months after retreatment, the
      average was -0.36 +/- 1.05 D in group I, -0.42 +/- 1.12 D in group II, and -1.40
      +/- 1.62 D in group III. CONCLUSION: The amount and frequency of regression was
      higher in patients with high and extreme myopia; however, the preliminary results
      of retreatment of regression were satisfactory.

PMID- 9571553
TI  - Effect of decreasing surface and interface irregularities after photorefractive
      keratectomy and laser in situ keratomileusis on optical and functional outcomes.
AB  - PURPOSE: To assess a new method for decreasing corneal ablated surface
      irregularities after photorefractive keratectomy (PRK) and laser in situ
      keratomileusis (LASIK) by performing a final smoothing immediately after the
      treatment. METHODS: One hundred forty-seven eyes with ablation irregularities
      after PRK or LASIK using the Nidek ED-5000 excimer laser and examined with the
      Nidek EAS 1000, were randomized into two groups: 74 eyes had final smoothing and
      73 eyes were patched immediately. Preoperative mean refraction for the smoothing
      group was -7.55 +/- 2.50 D and for the patched group, it was -7.30 +/- 1.90 D, (p
      = 0.04). RESULTS: AT 12 months after treatment, mean haze was 0.5 +/- 0.3 in the
      smoothing group and 1.2 +/- 0.4 in the patched group (p = 0.006); mean spectacle
      corrected visual acuity was 1.1 +/- 0.25 in the smoothing group and 0.95 +/- 0.18
      in the patched group (p = 0.02); the percentages of eyes within 1.00 D of the
      planned correction was 68% in the smoothing group and 33% in the patched group.
      CONCLUSION: Performing a final smoothing immediately after PRK or LASIK improves
      refractive and optical outcomes.

PMID- 9571554
TI  - A method for examining surface and interface irregularities after photorefractive
      keratectomy and laser in situ keratomileusis: predictor of optical and functional
      outcomes.
AB  - PURPOSE: To develop a system for the examination of the ablated surface after
      photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) and to
      correlate the surface regularity to the functional outcome. METHODS: A Nidek Eas
      1000 Anterior Eye Segment Analysis System was used to examine the ablated surface
      or the interface regularity immediately after PRK and LASIK. Eighty eyes were
      evaluated and divided into three study groups; group 1; regularity (18 eyes),
      group 2; mild irregularity (32 eyes) group 3; severe irregularity (30 eyes).
      RESULTS: At 12 months postoperatively, group 1 (regularity) showed the best
      percentage of eyes with 0 haze (100%) and with a refraction +/- 1.00 D of plano
      (89%); group 2 (mild irregularity) 84% had 0 haze and 62% were +/- 1.00 D of
      plano; group 3 (severe irregularity) 27% had 0 haze and 47% were +/- 1.00 D of
      plano. CONCLUSION: The patients with no postoperative irregularity had a sharply
      lower incidence of haze and a better refractive outcome with respect to plano,
      confirming the influence of ablation regularity on the results and the importance
      of this analysis in clinical practice.

PMID- 9571556
TI  - Histopathology of corneal wound healing after photorefractive keratectomy in
      rabbit eyes.

PMID- 9571555
TI  - Efficacy of topical nonsteroidal drops as pain relief after excimer laser
      photorefractive keratectomy.
AB  - PURPOSE: To compare the efficacy of topical aqueous indomethacin and ketorolac
      for pain relief following excimer laser photorefractive keratectomy (PRK).
      METHODS: We conducted a double masked, randomized trial involving 120 patients.
      All patients received a standard regimen of one of the trial drugs and
      chloramphenicol ointment to be used four times daily for 2 days. Pain levels and
      quality were assessed on a 10 cm linear analogue scale prior to each instillation
      of the topical medication with the McGill pain questionnaire. Pain threshold was
      evaluated using a modified State Trait Anxiety Inventory questionnaire. Patients
      were advised to use paracetomol for additional pain relief but were allowed to
      use any oral analgesic (except nonsteroidal agents) which they documented (type
      and quantity). RESULTS: There was no significant difference in pain scores
      between the groups using indomethacin and ketoralac. CONCLUSION: We found no
      significant difference between topical ketoralac and aqueous indomethacin as pain
      relief following excimer laser PRK. Both drugs seemed to significantly reduce
      pain.

PMID- 9571557
TI  - Comparison of 18% ethanol and mechanical debridement for epithelial removal
      before photorefractive keratectomy.
AB  - PURPOSE: To assess the safety of alcohol compared to mechanical debridement for
      epithelial removal prior to photorefractive keratectomy (PRK). METHODS: Forty-one
      second eyes of 41 patients underwent epithelial removal using alcohol prior to
      PRK with a Nidek EC-5000 excimer laser. The results were compared with the
      results of the 41 first eyes of the same patients that had mechanical
      debridement. RESULTS: Initial results showed that the alcohol treated group
      tended to stay slightly hyperopic but had less haze compared to the mechanical
      debridement group. The treating surgeons favored alcohol as the preferred method
      of epithelium removal. CONCLUSION: Alcohol debridement is an effective procedure
      although algorithms may have to be altered to take into account the slightly
      different healing process postoperatively.

PMID- 9571558
TI  - Accuracy of visual correction in photorefractive keratectomy.
AB  - PURPOSE: To investigate the accuracy of preoperative optical assessment and other
      factors that influenced the final visual outcome after photorefractive
      keratectomy (PRK). METHODS: The records of 126 eyes from 54 male and 72 female
      eyes were studied retrospectively, ranging from 6 months to 3 years post-PRK.
      Refractive errors ranged from low to high myopia and astigmatism, and proper and
      careful preoperative selection of patients was made. A single standard ablation
      zone (AZ) of 6.00 mm and transition zone (TZ) of 7.00 mm was made in all cases.
      RESULTS: The study population showed a high degree of accuracy in visual outcome.
      In simple myopia, 92.3% of female eyes and 84.1% of male eyes had a visual acuity
      of more than 6/9 or better. In myopia with astigmatism, 83.05% of female and
      65.9% of male eyes had a visual acuity of 6/9 (20/40) or better. However, despite
      the residual myopia, whether with or induced astigmatism, post PRK visual acuity
      seemed to be less influenced by it, than as in the pre-PRK status. CONCLUSION:
      This study showed an accuracy in visual outcome of > 90% for females and > 80%
      for males. The Nidek EC-500 was satisfactory for its purpose.

PMID- 9571559
TI  - Zonal photorefractive keratectomy for presbyopia.
AB  - PURPOSE: We performed zonal excimer laser photorefractive keratectomy in three
      eyes of three presbyopic patients using a specially designed mask, with a minimum
      follow-up of 24-months. METHODS: Two females (ages 59 and 48) and one male (age
      55) were included in the study. The procedure was performed with a mask designed
      by one of the authors (GMN), applied to the Aesculap-Meditec Mel 60 excimer
      laser. The mask consists of a mobile diaphragm formed by two blunt blades. The
      aim in all the eyes was a presbyopic correction of 3.00 D. RESULTS: After an
      initial regression of 1.00 D, the presbyopic correction remained stable during
      the 36-month follow-up. The patients read at least J3 at normal reading distance
      without correction. Since the ablated zone was only about 15% of the total area
      of a 3.0 mm pupil, all three patients were also able to read with their
      preoperative presbyopic correction (using the untreated 85% of the pupillary
      area). CONCLUSION: Although only three eyes were treated with the zonal
      presbyopia mask presented here, the visual and refractive outcome appears
      promising in view of the relatively long follow-up time.

PMID- 9571560
TI  - Multizone and transition zone photorefractive keratectomy for high myopia.
AB  - BACKGROUND: Variations in ablation profile may alter the stability of refraction
      and cause adverse effects in photorefractive keratectomy. We compared the
      benefits of multizone and transition zone ablation in the treatment of high and
      extreme myopia. METHODS: A scanning excimer laser system, Nidek EC-5000 was used
      with three-zone treatment and our results were compared retrospectively with
      results obtained in a group with a conventional ablation profile using a
      transition zone. RESULTS: Six-month follow-up data were available for 65 eyes
      with a transition zone and 46 eyes with three-zone treatment. Postoperative mean
      (+/- SD) healing time was 2.98 days (+/- 0.12) and 3.02 days (+/- 0.15) and night
      vision disturbances were 16% and 11.5% respectively, (p > 0.05). Refractive
      regression was also similar in the two groups; uncorrected visual acuity of 20/40
      or better was 90.77% and 89.14%. At 6 months postoperatively, the mean (+/- SD)
      corneal clarity score was 0.61 (+/- 0.29) in the transition zone group, and 0.51
      (+/- 0.07) in the multizone group (p < 0.05). CONCLUSION: No discernible
      differences between treatments were found in either epithelial healing or
      refractive outcome, such as regression, between the groups. Corneal haze was less
      in eyes treated with three-zone ablation.

PMID- 9571561
TI  - Satisfaction after photorefractive keratectomy.
AB  - PURPOSE: To evaluate patient satisfaction one year after photorefractive
      keratectomy (PRK) for myopia and myopia astigmatism using the Nidek EC-5000
      excimer laser. METHODS: This study assessed the level of satisfaction of 6280
      patients who underwent PRK after a minimum follow-up of 1 year. All patients were
      asked to enter their level of satisfaction as excellent, good, worthwhile, or
      disappointed into a networked computer database. Their responses were
      subsequently analyzed according to baseline and postoperative refractive data.
      RESULTS: Patients considered their results to be as follows: 82.3% good or
      excellent, 14.9% worthwhile, and 2.8% were disappointed with the outcome.
      CONCLUSION: A high percentage of patients were satisfied with the outcome
      following PRK. However, a fair number (14%) of patients considered the treatment
      to be worthwhile but it did not meet their expectations. Extensive counseling and
      inculcating realistic expectations before treatment is essential in achieving
      better patient satisfaction.

PMID- 9571562
TI  - Photorefractive keratectomy for myopia with -8.00 diopter cylindrical correction.
AB  - PURPOSE: A colleague requested PRK. The last time the patient was seen, no
      spectacles or contact lenses were worn. However, subjective refraction was -7.00 
      5.50 x 165 degrees. The original Nidek nomogram would have suggested setting the
      laser at the actual refraction. Our algorithm adjustments suggested a 40% extra
      correction of cylinder would be required. The laser was therefore set to -3.50 
      8.00 x 165 degrees aiming for a -1.00 -2.00 x 165 degrees outcome to allow for
      possible retreatment. METHODS: A 165 micron depth ablation was performed. RESULTS
      AND CONCLUSION: At 6 weeks after surgery, visual acuity was 0.63 unaided with a
      refraction of +1.50 -1.75 x 170 degrees on pred forte.

PMID- 9571563
TI  - Corneal transparency and measurement of corneal permeability in excimer laser
      photorefractive keratectomy.
AB  - PURPOSE: To introduce an image analysis of the cornea in photorefractive
      keratectomy (PRK) for preoperative and early postoperative determination of
      changes in the condition of the cornea. METHODS: Slit-lamp videography was used
      to evaluate the cornea. Microdensitometry of the corneal images was performed.
      The optic density of the anterior, middle, and posterior corneal layers was
      measured. Photorefractive keratectomy was performed with the Nidek EC-5000
      excimer laser. We followed patients with different amounts of myopia (range, 
      1.00 to -20.00 D) classified into three groups, according to age. Each age group
      was divided into four subgroups depending on the amount of myopia. RESULTS: The
      analysis of the microdensitometry results of the optic section of transparent
      corneas in myopic patients demonstrated differences depending on age and mean
      amount of myopia. A correlation between the microdensitometric data of
      permeability by fluorescein and the refractive results of PRK was found.
      CONCLUSION: Quantitative image analysis of the cornea is a useful method to
      evaluate the condition of the cornea before and after PRK. This method can
      identify early damage to the cornea in myopia patients. Preoperative
      investigation of permeability of the cornea using fluorescein is an important
      method for selection of the patients for PRK.

PMID- 9571564
TI  - Mechanism of ovarian autoimmunity: induction of T cell and antibody responses by
      T cell epitope mimicry and epitope spreading.
AB  - Autoimmune diseases are often manifested as organ inflammation with loss of
      function, and detectable autoreactive T cell and autoantibody responses. In the
      proper genetic context, we have shown that these parameters of autoimmunity can
      result from a single pivotal event: the induction of a strong and persistent T
      cell response for a foreign or unrelated self peptide that mimics the target self
      peptide. This may apply to organ-specific and systemic autoimmunity, independent
      of whether the tissue inflammation results from T cell immune mechanism or
      antibodies. T cell peptide mimicry, through sharing of critical residues or by a
      less defined mechanism, can result in autoimmune disease. Once triggered, the
      helper T cell response leads rapidly to a concomitant autoantibody response
      spreading to distant B cell determinants of the self protein antigen. Evidently,
      with T cell help, endogenous antigens can stimulate B cells to provoke a
      functional autoantibody response against conformational antigenic determinants.
      These findings are based on recent studies on a novel autoimmune ovarian disease
      model induced by a self peptide with well-defined T and B cell epitopes. However,
      studies reported on systemic lupus erythematosus models have shown that similar
      events may result in autoantibody response in systemic autoimmunity.

PMID- 9571565
TI  - Regulation of MHC class I gene expression is at transcriptional and post
      transcriptional level in bovine placenta.
AB  - A previous study of MHC in cattle trophoblast demonstrated low or absent class I
      expression, using a broad specificity monoclonal antibody. The study reported
      here uses MHC-defined cattle and embryo transfer to ensure MHC incompatibility
      between dam and calf. Transcription and expression of defined class I genes was
      examined in placentomes taken at term, using monoclonal antibodies to bovine
      class I, a gene-specific DNA-based typing system, and in situ hybridisation.
      Results demonstrate intermediate levels of fetal MHC class I mRNA in trophoblast,
      but no detectable fetal class I protein. This suggests a level of transcriptional
      down-regulation, and a post-transcriptional block which might involve other gene
      products, such as beta2-microglobulin (beta 2m), or proteins involved in
      generation/transport of peptides.

PMID- 9571566
TI  - Ovine trophoblast interferon enhances MHC class I expression by sheep endometrial
      cells.
AB  - Type I interferons have a variety of important immunological functions, including
      effects on expression of class I molecules of the major histocompatibility
      complex (MHC). Interferon-tau (IFN-tau) is an important anti-luteolytic factor
      produced by the trophoblast of ruminants. Ovine endometrial cells were cultured
      with recombinant ovine IFN-tau and stained with monoclonal antibodies specific
      for ovine MHC class I molecules. The expression of MHC class I was then
      determined by immunocytochemical or immunofluorescent staining using microscopy
      or flow cytometry. IFN-tau was found to enhance the expression of MHC class I
      molecules on the endometrial cells, as did recombinant IFN-alpha. No significant
      effects on MHC class II expression were observed. These findings may have
      important implications for cellular interactions associated with immunological
      aspects of pregnancy.

PMID- 9571568
TI  - Interleukin-1 beta fragment (163-171) modulates bovine granulosa cell
      proliferation in vitro: dependence on size of follicle.
AB  - The biological effects of IL-1 on ovarian function have been considered as an
      inflammatory-like reaction. The peptide fragment of IL-1 (163-171 aa), which
      belongs to the active site of the whole protein, has been shown to exert an
      immunostimulatory activity without inducing inflammatory effects. The aim of this
      study was to investigate whether IL 163-171, alone or associated with bFSH,
      modulates granulosa cell proliferation; in addition, we wanted to assess if IL
      163-171 interferes with FSH binding to receptors. Bovine follicles were divided
      according to their size. Cell proliferation, assessed by [3H]-thymidine uptake
      and [125I]-FSH binding, were studied in cells treated with IL 163-171(0, 0.5, 5
      and 20 ng/ml) with or without bFSH (100 ng/ml) for 24, 48 or 72 h. Basal
      incorporation of [3H]-thymidine into granulosa cells from small follicles was
      always 3-fold higher (P < 0.01) than that by cells from large follicles. IL 163
      171 did not show any effect in granulosa cells from large follicles but
      stimulated (P < 0.01) [3H]-thymidine uptake into granulosa cells from small
      follicles; furthermore IL 163-171 interacted positively with bFSH (P < 0.01)
      after 48 and 72 h. IL 163-171 significantly reduced (P < 0.05) FSH binding in
      cells from small follicles after 24 h, but not after 48 and 72 h. This data
      demonstrates that: (1) Follicular size and cell proliferation are inversely
      related; (2) IL 163-171 modulates granulosa cell proliferation only in cells from
      small follicles; and (3) the interaction between IL 163-171 and FSH does not
      mainly occur at receptor level.

PMID- 9571569
TI  - Differential expression of interleukin-1 beta and interleukin-6 in human fetal
      serum and meconium-stained amniotic fluid.
AB  - The study was designed to investigate the expression of the inflammatory
      cytokines interleukin-1 beta and interleukin-6 in meconium-stained amniotic fluid
      and in fetal cord serum. Amniotic fluid and fetal cord serum specimens were
      collected from 10 and 9 women with meconium-stained and clear amniotic fluid,
      respectively, during Caesarean operation at labor The mean concentrations of
      interleukin-1 beta found in clear and meconium-stained amniotic fluid were 10.0
      and 54.5 pg/ml, respectively, and the difference was not statistically
      significant. On the other hand, the concentrations of interleukin-6 in meconium
      stained amniotic fluid (774 pg/ml) was significantly higher than that found in
      clear amniotic fluid (149 pg/ml) (P = 0.0036). The differences of levels of both
      interleukin-1 beta and interleukin-6 in fetal cord serum specimens were not
      significant between neonates born to mothers with either clear or meconium
      stained amniotic fluid (P = 0.8702 and 0.2987, respectively). The results of this
      study suggest that the production of at least one of the inflammatory cytokines,
      interleukin-6, is associated with the meconium found in amniotic fluid.

PMID- 9571567
TI  - Fertility of brushtail possums (Trichosurus vulpecula) immunised against sperm.
AB  - The brushtail possum (Trichosurus vulpecula) is a major pest species in New
      Zealand. Research to develop a possum-specific method of immunologically-based
      fertility control (immunocontraception) has begun. This study examined the effect
      of immunization against sperm on the fertility of possums. Possums were assigned
      to 16 mating groups (two females and one male per group) before the start of the
      breeding season. One female in each group and eight males were injected
      subcutaneously with 5 x 10(7) sperm in complete Freund's adjuvant. Animals were
      given booster injections containing 5 x 10(7) sperm in incomplete Freund's
      adjuvant 4 and 12 weeks later. Control animals received adjuvants emulsified with
      phosphate buffered saline. Serum and sperm samples were collected monthly and the
      number of offspring recorded. Reproductive tract samples were collected from
      eight immunized and eight control possums of each sex at the end of the breeding
      season. Samples were screened for sperm antibody binding by an indirect possum
      sperm ELISA. Increased sperm antibody binding was detected in sera of 22 (15
      females and seven males) of the 24 animals immunized against sperm. Immunization
      significantly reduced the proportion of females producing offspring (2/16
      immunized versus 12/16 control) but had no effect on the fertility of males.
      Immunization increased sperm antibody binding activity in vaginal secretions of
      female and in prostatic tissue of male possums. Results indicate that there are
      antigens in possum sperm with immunocontraceptive potential for possum control.

PMID- 9571570
TI  - The relationship between amniotic fluid macrophage colony-stimulating factor and
      fetal growth.
AB  - The aim of this study was to clarify whether amniotic fluid macrophage colony
      stimulating factor (M-CSF) is related to placental development and fetal growth.
      Maternal serum and amniotic fluid M-CSF levels were analyzed in 22 pregnant women
      (seven intrauterine growth retardation (IUGR) complicated and 15 normal
      pregnancies) at 33-40 weeks' gestation. Amniotic fluid was obtained by
      transabdominal amniocentesis performed under ultrasonographic guidance. The mean
      amniotic fluid M-CSF level of the IUGR-complicated pregnancy group (5.0 +/- 1.4
      ng/ml) was significantly lower (P < 0.05) than that of the normal pregnancy group
      (7.4 +/- 1.6 ng/ml). All the IUGR-complicated pregnant women subsequently
      delivered small-for-gestational-age (SGA) infants with significantly lower
      placental weights than those of the normal infants. There was no significant
      correlation between amniotic fluid M-CSF levels and gestational age in the normal
      pregnancy group. The same scattergram showed the amniotic fluid M-CSF levels of
      the IUGR-complicated pregnancy group tended to be lower than those of the normal
      pregnancy group at 33-40 weeks' gestation. The results suggested that amniotic
      fluid M-CSF was one of the regulators of human placental development and was
      related to fetal growth.

PMID- 9571571
TI  - Seminal plasma immunoglobulin concentrations in autoimmune male subfertility.
AB  - The presence of anti-sperm antibodies (ASAs) in seminal plasma is associated with
      infertility. They have been shown to reduce sperm motility, interfere with
      cervical mucus penetration and gamete interaction, and have been shown to reduce
      spontaneous fertilization and pregnancy rates. Although some causes can be
      determined, in the majority of cases the initial event causing the immune
      sensitisation and the reasons for the continuing antibody secretion remains
      unknown. Quantitative determination of total IgG, IgA and IgM within seminal
      plasma had not been previously reported in patients with and without specific
      ASAs. Semen samples from 512 men presenting with infertility were analyzed. One
      hundred and forty-six men (28.5%) had seminal fluid ASAs as determined by the MAR
      or TAT tests. The total seminal plasma IgG and IgA concentrations were
      significantly elevated in the ASA-positive groups compared with ASA-negative
      groups (IgG: 8.83 mg/100 ml vs. 7.15, P = 0.0008; and IgA: 2.88 mg/100 ml vs.
      1.64, P = 0.0001). Only 19 samples showed seminal fluid IgM, and there was no
      difference between the ASA positive or ASA negative samples. The significance of
      these findings is discussed.

PMID- 9571572
TI  - Diffusion of CDC's Guidelines to Prevent Tobacco Use and Addiction.
AB  - The Center for Disease Control and Prevention's School Guidelines to Prevent
      Tobacco Use and Addiction were developed, in part, to assist state and local
      education agencies in adopting and implementing effective school-based tobacco
      prevention and cessation programs. This project assessed state education agency
      awareness of and reaction to the Guidelines, and documented efforts to
      disseminate the Guidelines to local schools. Key informants in 15 state education
      agencies were interviewed. Respondents reported a fairly high level of
      receptivity to the Guidelines, numerous benefits and few barriers, and high
      commitment. Levels of use for the Guidelines varied. Dissemination strategies
      such as mass mailing or teleconferences are not sufficient to influence the use
      and integration of Guidelines for school health. The diffusion process requires
      planned change over time through numerous communication channels and should be
      monitored at the national, state, and local levels to assess effectiveness and
      impact.

PMID- 9571573
TI  - Development of an intervention map for a parent education intervention to prevent
      violence among Hispanic middle school students.
AB  - This paper describes development of Padres Trabajando por la Paz, a violence
      prevention intervention for Hispanic parents to increase parental monitoring. The
      intervention was developed using an innovative new program planning process:
      intervention mapping. Theory and empirical evidence broadly defined performance
      objectives and determinants of parental monitoring. These objectives were further
      refined through group and individual interviews with the target parent group.
      Learning objectives for the intervention guided the content of the intervention
      that used modeling as the primary method and role model stories as a strategy
      delivered through newsletters. Stage-matching members of the target population
      for their readiness to implement the parental monitoring behaviors further
      refined the social cognitive message design strategies. Intervention mapping
      provides an explicit theory- and data-driven guide for intervention development
      that maximizes intervention impact for a specific target population.

PMID- 9571574
TI  - Establishing a research agenda for school nursing.
AB  - During 1996, representatives from two professional organizations--American School
      Health Association and National Association of School Nurses--met collaboratively
      to identify and rank order key questions regarding contemporary research needs in
      school nursing services. This article summarizes existing literature and proposes
      areas for research. Recommendations are offered for nurses, school health program
      administrators, educators of school nurses, professional organizations, and
      others who plan and provide health care for school-aged youth.

PMID- 9571575
TI  - Bienestar: a diabetes risk-factor prevention program.
AB  - The Bienester Health Program, a diabetes risk-factor prevention pilot program,
      targeted fourth grade Mexican American children. The primary goals are to
      decrease the two established risk factors for diabetes--overweight and dietary
      fats. Since the health program is based on Social Cognitive Theory, on social
      systems structure, and on culturally relevant material, it considers the child's
      social systems on both its health program and process evaluation. Learning
      activities were developed for four social systems that potentially influence
      children's health behaviors (parent, classroom, school cafeteria, and after
      school care). Preliminary results show that the Bienestar Health Program
      significantly decreased dietary fat, increased fruit and vegetable servings, and
      increased diabetes health knowledge.

PMID- 9571576
TI  - Relationship of adolescent self-esteem to selected academic variables.
AB  - This study investigated whether self-esteem precedes various academic behaviors
      and beliefs among 593 high school students (63.7% female, 60.9% African
      American). Measures of home and school self-esteem, grade point average,
      perceived academic standing and progress, and educational plans were collected by
      survey and archival review of grade and attendance records at the beginning (pre
      test) and end of the school year (post-test). Self-esteem and academic variables
      differed by gender, race, and guardianship. Self-esteem related significantly to
      academics and absenteeism. Results suggest selected academic variables predict
      self-esteem even when the effects of gender, race, and guardianship are removed
      and pretest self-esteem scores are controlled. In conclusion, student academic
      performance influences subsequent academic and home self-esteem. Creation of
      positive academic experiences for youth may be a critical activity, since experts
      contend that low self-esteem is associated with subsequent behavioral problems.
      The markedly lower self-esteem of Native American and Hispanic youth warrants
      further investigation.

PMID- 9571577
TI  - Promoting emotional health through haiku, a form of Japanese poetry.
AB  - This teaching technique can be adapted to use with young children. The use of
      rhymes may be easier and more fun for younger students. Also, this teaching
      technique can be used to address numerous health issues, which makes it
      appropriate for all health content areas. In addition to using student selections
      that illustrate various emotions, other resources are available for this
      activity. Libraries and bookstores offer wide selections of books containing
      poetry and quotations. In addition to books about haiku, consider general poetry
      selections by Maya Angelou, e.e. cummings, Ogden Nash, and Shel Silverstein.
      Musical selections can represent different styles, such as the Beatles'
      "Yesterday"; Blind Melon's "Change"; Garth Brooks' "The Dance"; Eric Clapton's
      "Tears from Heaven"; Gloria Estefan's "Coming Out of the Dark"; Whitney Houston's
      "Emotional" and "I Will Always Love You"; and Elton John's "Circle of Life."
      Internet sites also can be accessed for poetry samples (see Internet Resources).
      An Internet resource for ordering discounted books, including selections about
      haiku and poetry, is Amazon.com--Earth's Largest Book store, at
      http:www.amazon.com/exec/obidos/ subst/home/home.html/0184-8423170-571096.

PMID- 9571578
TI  - Amblyopia: the silent thief.

PMID- 9571579
TI  - Using point-of-sale technology in the school lunch room.

PMID- 9571580
TI  - Utility of three-dimensional ultrasound Doppler flow reconstruction of the
      proximal jet to quantify effective orifice area: in vitro steady and pulsatile
      flow studies.
AB  - We examined the utility of three-dimensional (3D) reconstruction of two
      dimensional color Doppler images of the proximal jet to quantify the effective
      area of an orifice in an in vitro model. Steady and pulsatile flows were directed
      through various orifices; orifice vena contracta areas were quantified with laser
      flow visualization, thus providing gold standard effective orifice areas. Three
      dimensional areas followed vena contracta areas well, although variations in
      color Doppler gain and 3D gray levels for thresholding produced significant
      changes in reconstructed images. These variations were minimized by using minimum
      color gain and 50% gray level threshold. At these settings, 3D areas still
      overestimated vena contracta areas by approximately 25% because of the poor
      lateral resolution of the color Doppler system, which caused bleeding of the flow
      signal past the edges of the proximal jet. Nevertheless, 3D flow images provided
      a superior format for qualitative and quantitative appreciation of proximal jet
      shape and dimensions.

PMID- 9571581
TI  - Estimation of mitral regurgitation with a hemielliptic curve-fitting algorithm:
      in vitro experiments with native mitral valves.
AB  - To date, studies on the mitral flow convergence method have used rigid, circular,
      or slit orifices to represent the regurgitant orifice. In this study, explanted
      porcine mitral valves, with the entire mitral apparatus preserved, were mounted
      in an in vitro model to reproduce the three-dimensional regurgitant orifice
      geometry while permitting close control and measurement of the experimental
      conditions. This experimental setup permitted the evaluation of the hemispheric
      and hemielliptic formulas under realistic physiologic conditions. In this study,
      a heart rate of 70 beats/min was used with cardiac outputs between 1.5 and 6
      L/min. Peak regurgitant flow rates ranged from 7 to 16 L/min (regurgitant jet
      velocities ranged from 2 to 5.5 m/sec); peak aortic flow rates ranged from 9 to
      30 L/min. Four native mitral valves were used for these studies for a total of 28
      stages. Although the hemielliptic modification has previously shown success in
      vitro and computationally, it has not been used clinically because of difficulty
      imaging the flow convergence region in three orthogonal planes. A curve-fitting
      algorithm was developed to extract the hemielliptic dimensions from two standard
      ultrasound views by rotating the transducer 90 degrees. Improved agreement was
      obtained between true and calculated flow rates by the hemielliptic formula (y =
      1.02 x + 0.29; r = 0.91) compared with the hemispheric formula (y = 1.18 x - 2.2;
      r = 0.66). This method provides accurate results with a realistic three
      dimensional regurgitant orifice geometry and has the capability of being
      incorporated as a function key on an ultrasound machine for clinical application.

PMID- 9571582
TI  - What is the validity of continuous wave Doppler grading of aortic regurgitation
      severity? A chronic animal model study.
AB  - Continuous wave Doppler methods have been widely used clinically for evaluating
      the severity of aortic regurgitation; however, there have been no studies
      comparing these continuous wave Doppler methods with a strictly quantifiable
      reference for regurgitant severity. The purpose of this study was to test the
      applicability of continuous wave Doppler methods (deceleration slope and pressure
      half-time) for evaluation of chronic aortic regurgitation in an animal model.
      Eight sheep were studied 8 to 20 weeks after surgery to create chronic aortic
      regurgitation. Twenty-nine hemodynamically different states were obtained
      pharmacologically. A Vingmed 775 system was used for recording continuous wave
      Doppler traces with a 5 MHz annular array transducer directly placed on the heart
      near the apex. The aortic regurgitation was quantified as peak and mean
      regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions
      determined with pulmonary and aortic electromagnetic flow probes and meters
      balanced against each other. Peak regurgitant flow rates varied from 1.8 to 13.6
      L/min (6.3 +/- 3.2 L/min) (mean +/- SD), mean regurgitant flow rates varied from
      0.7 to 4.9 L/min (2.7 +/- 1.3 L/min), regurgitant stroke volume varied from 7.0
      to 48.0 ml/beat (26.9 +/- 12.2 ml/beat), and regurgitant fraction varied from 23%
      to 78% (53% +/- 16%). Only marginal correlations were obtained between reference
      indexes and continuous wave Doppler deceleration slope and pressure half-time (r
      = 0.55 to 0.74). A deceleration slope greater than 3 m/sec2 and pressure half
      time less than 400 msec did, however, provide 100% specificity for detecting
      severe AR (regurgitant fraction > 50%). Our study shows that the continuous wave
      Doppler deceleration slope and pressure half-time methods have limited use for
      quantifying aortic regurgitation.

PMID- 9571583
TI  - Autonomous epicardial and endocardial boundary detection in echocardiographic
      short-axis images.
AB  - An autonomous endocardial and epicardial boundary detection (ABD) method is
      reported. One hundred ten cycles from 55 clinical studies were selected
      retrospectively. Image sequences were digitized at 512 x 480 pixel resolution.
      The point-by-point boundary positions of the ABD and the areas enclosed were
      compared with positions and enclosed areas drawn by three independent observers.
      Correlation coefficients for epicardial end-diastolic (ED) and end-systolic (ES)
      areas, endocardial ED and ES areas, muscle area, and fractional area change were
      0.970, 0.976, 0.951, 0.985, 0.887, and 0.878, respectively. Bland-Altman analysis
      showed negligible biases with standard deviations comparable to those of the
      observers. The mean difference between the ABD border and the consensus observer
      border positions in 64 directions falls within the mean range of interobserver
      border positions, suggesting that shape is also well defined by the ABD.

PMID- 9571584
TI  - Diastolic dysfunction in young patients with insulin-dependent diabetes mellitus
      as determined by automated border detection.
AB  - Diastolic dysfunction is an early harbinger for systolic dysfunction in insulin
      dependent diabetes mellitus (IDDM). To determine the role of automated border
      detection (ABD) in detecting diastolic abnormalities and whether IDDM control
      correlates with abnormalities, 21 young IDDM patients (22 +/- 4 years old) and 19
      control subjects underwent echocardiography. ABD indices included the percent
      contribution to total left ventricular filling of the three phases of diastole
      (rapid filling, diastasis, and atrial contraction) and peak filling rate. Doppler
      indices included E/A ratio and peak filling rate. Rapid filling phase was lower
      in the IDDM patients compared with control subjects (73% +/- 5% versus 80% +/-
      5%, p = 0.0006), and atrial contraction filling was higher (19% +/- 4% versus 14%
      +/- 3%, p = 0.0003). Doppler indexes showed similar changes. Glycosylated
      hemoglobin, insulin dosage, and duration of IDDM since puberty were associated
      with filling abnormalities. Young patients with IDDM have increased atrial
      contraction and reduced rapid filling phases detected by automatic border
      detection, and these diastolic abnormalities are related to the diabetic disease
      process.

PMID- 9571585
TI  - A method for detecting changes in left ventricular mass during variations in
      filling volume.
AB  - Two-dimensional echocardiography has been useful for measuring changes in left
      ventricular mass (LVM) at constant left ventricular end-diastolic volume (LVEDV).
      Two-dimensional echocardiographic measurement of LVM changes during variations in
      LVEDV requires definition of the LVM/LVEDV relation because two-dimensional
      echocardiographic measurements could be affected by asymmetrical redistribution
      of LVM. Echocardiography data were recorded during caval occlusions in pigs (n =
      6). Results confirm that A(M) (left ventricular [LV] short-axis cross-sectional
      [SACS] wall thickness area), was inversely related to AL (LV SACS lumen area),
      the average relation being A(M) = -0.33 AL + 20 (r = 0.82 +/- 0.05 [SE]). In
      addition, we developed a model that computes normal relation between LV SACS wall
      thickness area (AMc) and LV SACS lumen area (ALc) over a physiologic range of
      LVEDVs based on a single end-diastolic two-dimensional echocardiographic SACS
      image. Each computed relation corresponds uniquely to an LVM (LVMc).
      Theoretically, a difference between AMc/ALc relation before an intervention and
      the computed relation after the intervention would indicate a change in LVM. To
      test the utility of this model, edema was induced in a second group of pigs (n =
      6) by coronary hemodilution. Two conditions were tested: pre-edema and edema.
      Serial AMc/ALc and LVMc were computed. Pre-edema and edema AMc were compared at
      matched LV SACS end-diastolic areas (ALc = 15 cm2). Results showed a significant
      increase in LVMc (two-tailed p value < 0.05), as observed by two-dimensional
      echocardiography. We conclude that the A(M) and AL are inversely related. This
      relation is useful for detecting alterations in LVM during variations in LVEDV.

PMID- 9571586
TI  - Bilateral atrial function after chemical cardioversion of atrial fibrillation
      with amiodarone: an echo-Doppler study.
AB  - Cardioversion of atrial fibrillation transiently increases the risk of embolism
      presumably by decreased atrial mechanical function. It has been suggested that a
      component of early dysfunction relates to the mode of cardioversion. Amiodarone
      is one of the drugs used to restore sinus rhythm in patients with atrial
      fibrillation. However, the effect of this drug on left and right atrial
      mechanical function after conversion to sinus rhythm is not well known. Thirty
      one patients (group AF) cardioverted from atrial fibrillation with intravenous
      amiodarone (average dose 1 gm/day) were prospectively studied to examine the
      effect of this drug on recovery of left and right atrial mechanical function.
      These patients were compared with 17 consecutive individuals without evidence of
      cardiac disease who became our control group (group C). Transmitral flow
      velocities and echocardiographic parameters were recorded within 24 hours after
      cardioversion and on the seventh day in group AF and one time in group C. Left
      and right atrial ejection force to evaluate atrial mechanical function was
      defined as 0.5 x 1.06 x mitral (m) or tricuspid (t) orifice area x (m or t peak A
      velocity)2. If this value in group AF was more than the mean minus 1 standard
      deviation of control group data, atrial ejection function after cardioversion was
      considered normal. The two groups were similar with respect to age, sex, arterial
      blood pressure, heart rate, left ventricular diameters, and left ventricular
      ejection fraction. Left and right atrial size was higher in group AF (left: group
      AF, 18.1 +/- 3.9 cm2; group C, 11.3 +/- 2.5 cm2, p < 0.01; right: group AF, 14.9
      +/- 3.2 cm2; group C, 11.6 +/- 2.3, p < 0.01). Measurements of right and left
      atrial ejection force measured within 24 hours and on day 7 in group AF were
      similar to that in group C (left: group C, 11.9 +/- 5.3 kdyne; AF group, 24
      hours, 19.4 +/- 15.5 kdyne [NS]; AF group, day 7, 14.7 +/- 13.6 kdyne [NS];
      right: group C, 3.6 +/- 1.99 kdyne; AF group, 24 hours, 4.3 +/- 3.3 kdyne [NS];
      AF group, day 7, 3.5 +/- 2.9 kdyne [NS]). Therefore almost all patients
      undergoing cardioversion for atrial fibrillation with amiodarone recovered
      bilateral atrial mechanical function within 24 hours after cardioversion (26 of
      31-84%-left atrial ejection force; 28 of 31-93.5%-right atrial ejection force),
      with normal left atrial function in 97% of patients and normal right atrial
      function in 100% of patients on day 7 after conversion to sinus rhythm. These
      findings may have significant implications on postcardioversion anticoagulation
      strategies.

PMID- 9571587
TI  - Morphometric assessment of the innominate vein in the prediction of persistent
      left superior vena cava.
AB  - This study sought to develop a simple echocardiographic predictor of persistent
      left (L) superior vena cava (SVC) in subjects with bilateral SVC. Two groups of
      children were studied: one with known LSVC (n = 19) and the other, a control
      group, without LSVC (n = 15). Both groups were of similar age (3.5 +/- 3.0, mean
      +/- SD vs 3.8 +/- 3.1 years; p = 0.8) and weight (14.6 +/- 7.1 vs 15 +/- 8 kg; p
      = 0.9). The left innominate vein was either absent (n = 11) or hypoplastic (n =
      8) in the LSVC group. The ratio of the innominate vein to the innominate artery
      was found to be independent of age or body surface area but was significantly
      smaller in the LSVC group than in the control group (0.33 +/- 0.1 vs 0.97 +/-
      0.1; p < 0.001). A cutoff value of 0.47 or less discriminated the LSVC group from
      the control subjects. Interobserver and intraobserver variations, although
      important, did not influence the discriminating value of the ratio in the
      diagnosis of LSVC. Validation of the proposed ratio in 30 consecutive
      prospectively studied patients with LSVC proved to be 100% sensitive in
      predicting LSVC. No false-positive diagnosis of LSVC was made when this principle
      was applied. Absent or hypoplastic left innominate vein measuring 0.47 or less of
      the innominate artery is an easily recognizable and reliable echocardiographic
      predictor of LSVC.

PMID- 9571588
TI  - Ultrasound evaluation of endovascular repair of abdominal aortic aneurysms.
AB  - Endovascular repair of an abdominal aortic aneurysm (AAA) offers a minimally
      invasive alternative to an open surgical procedure in selected patients. The
      purpose of this study was to examine the usefulness of ultrasonography for
      evaluating the results of endovascular repair. METHODS: We studied 17 patients
      who underwent endovascular repair. In 10 patients a bifurcated prosthesis was
      positioned below the renal arteries with the bifurcated branches in the iliac
      arteries. The other 7 patients had a nonbifurcated infrarenal prosthesis.
      RESULTS: In each patient the AAA and the entire prosthesis, including its
      bifurcated branches, were visualized. The mean AAA diameter was 5.0 +/- 0.6 cm.
      The mean prosthesis body diameter was 2.2 +/- 0.3 cm, and the diameters of the
      bifurcated limbs were 1.0 to 1.2 cm. Color Doppler studies revealed blood flow
      limited to the prosthetic lumen and its bifurcation in 16 patients; the space
      between the prosthesis and the AAA wall was clotted in these patients. In 1
      patient a communication was seen between the prosthesis and the AAA lumen through
      a dehiscence in the distal attachment. CONCLUSION: Ultrasonography is a simple,
      noninvasive tool for the evaluation of the results of endovascular repair of AAA
      and can detect complications of this procedure.

PMID- 9571589
TI  - Echogenic structures in the left atrioventricular groove: diagnostic pitfalls.
AB  - A variety of echogenic structures that can be detected by echocardiography in the
      left atrioventricular groove are best seen in the parasternal long-axis view and
      can be missed if not carefully looked for. Normal anatomic structures or variants
      can be seen, for example, dilated coronary sinus, persistent left superior vena
      cava, or lipomatous tissue. Degenerative or inflammatory processes of the mitral
      annulus (calcification of the mitral annulus, mitral annular abscess) and
      aneurysms of the left circumflex coronary artery or of the descending aorta can
      depict pathologic structures. Hiatal hernia and tumors can be found as well.

PMID- 9571590
TI  - Diagnostic aid of transesophageal echocardiography in an adult case of scimitar
      syndrome: confirmation of the findings at surgery and review of the literature.
AB  - The diagnosis of scimitar syndrome is straightforward when the scimitar vein is
      visible on the chest radiograph; however, a diagnosis is not definitive when this
      vein is obscured by dextroversion, and therefore other investigative modalities
      are needed. These methods include pulmonary angiography, computed tomographic
      scan, and magnetic resonance imaging, which have know limitations, and
      transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE),
      which are particularly useful because they are noninvasive, versatile, and
      accurate. TEE is superior to TTE in the diagnosis of this syndrome and other
      forms of partial anomalous pulmonary venous return. TEE should compliment TTE
      whenever the latter is of poor quality or the information is incomplete.
      Moreover, TEE is vital in both the perioperative evaluation of the repair and the
      confirmation of the patency of the pulmonary venous to left atrial anastomosis.
      The advantages of TEE are demonstrated by this case report, and its accuracy is
      confirmed at surgery.

PMID- 9571591
TI  - Pulsed wave and color Doppler echocardiography and cardiac catheterization
      findings in bilateral pulmonary vein stenosis.
AB  - Pulmonary vein stenosis is a rare condition that usually is congenital in origin;
      it is almost invariably fatal in its bilateral and severe forms. It is often
      overlooked, however, during clinical examination, routine echocardiography, and
      even at cardiac catheterization. This report describes the pulsed Doppler, color
      flow echocardiography, and hemodynamic findings of bilateral pulmonary vein
      stenosis that accompany ventricular septal defect and atrial septal defect
      corrected by surgery.

PMID- 9571592
TI  - Fatal pulmonary embolization of a right atrial mass during transesophageal
      echocardiography.
AB  - Transesophageal echocardiography is a semi-invasive diagnostic technique with a
      very low incidence of significant complications. Only two deaths related to the
      procedure have been reported in the literature. We present the case of a 46-year
      old man with a right atrial mass, presumably a cardiac myxoma. During attempts at
      esophageal intubation for a transesophageal echocardiography procedure, the mass
      fragmented and dislodged, causing massive pulmonary embolism and death. We
      believe that to avoid this potential complication, great care must be taken in
      the evaluation of patients with a right intracardiac mass by means of
      transesophageal echocardiography.

PMID- 9571593
TI  - Type II aortic dissection complicating discrete subvalvular aortic stenosis in an
      adult man.
AB  - We report a case of a 41-year-old man in whom discrete subaortic stenosis was
      complicated by a type II aortic dissection. Such an association has not been
      previously described. Diagnosis was readily achieved with echocardiography and an
      emergency repair was successful.

PMID- 9571594
TI  - Can climacteric women self-adjust therapeutic estrogen doses using symptoms as
      markers?
AB  - OBJECTIVES: To investigate if disappearance of climacteric symptoms during
      hormone replacement therapy (HRT) also means good therapeutic level of serum
      estradiol. The study group comprised of 32 postmenopausal women who had frequent
      climacteric symptoms. METHODS: The women increased the daily treatment doses of
      percutaneous estradiol every 2 weeks until they felt comfortable with it. Each
      woman continued at that treatment dose for up to 3 months. Blood samples for
      estradiol assay were drawn at baseline, every time before the estradiol dosage
      was increased and at the end of the study. Climacteric symptoms were scored
      according to the Kupperman menopausal index. RESULTS: Despite the relief of
      climacteric symptoms, serum estradiol concentration was at a menopausal level (<
      50 pg/ml) in 22% of the women. In all, 45% of the subjects showed serum estradiol
      remaining under 60 pg/ml, 29% of the women showed levels of 60-100 pg/ml and 26%
      showed serum estradiol concentration more than 100 pg/ml. CONCLUSIONS: The
      disappearance of climacteric symptoms during HRT does not guarantee that estrogen
      levels are sufficiently high for obtaining long term benefits of HRT.

PMID- 9571595
TI  - Prevalence, 1-year incidence and factors associated with urinary incontinence: a
      population based study of women 50-74 years of age in primary care.
AB  - OBJECTIVES: To study prevalence, incidence, remissions and factors associated
      with urinary incontinence in women 50-74 years of age. METHODS: Cross-sectional
      study of prevalence and associated factors and a 1-year prospective study of
      incidence and remissions. A random sample of 698 women were invited for a
      gynecological examination in general practice in three municipalities in Northern
      Norway in 1994-1995. Five hundred and seven (73%) met for the first consultation,
      489 of them for the second one. Questionnaires were answered by women and doctors
      during consultations at inclusion and 1 year later. Prevalence was estimated at
      three levels of evidence. RESULTS: Any leakage was reported by 47% and regularly
      by 31%. For 19%, leakage was objectively demonstrated and claimed to be a social
      or hygienic problem. Incontinence was associated with high body weight, with poor
      ability to contract pelvic floor muscles and with previous gynecological
      operations excluding hysterectomy. Three women (0.6%) developed regular
      incontinence during the year of investigation. There was no convincing case of
      spontaneous remission. CONCLUSION: Urinary incontinence is very frequent in women
      aged 50-74 years and about one in five are potential patients needing treatment.
      Urinary incontinence is an enduring condition with little tendency for remission
      without treatment.

PMID- 9571596
TI  - Compliance with hormone replacement therapy in Chinese women in Hong Kong.
AB  - Compliance with hormone replacement therapy (HRT) has been extensively studied in
      western countries. However, there is little data concerning women in Asian
      countries. A retrospective study was performed to determine compliance in a group
      of Hong Kong Chinese women who commenced HRT over a 2 year period. Two years
      after the commencement of HRT, 68.3% were still taking HRT, although not always
      in the original formulation. The highest drop out rate occurred during the first
      6 months. Factors which were associated with a higher degree of compliance were
      young age at menopause and at the time of initial consultation and the use of
      unopposed HRT. A number of significant medical problems were identified during
      the 2 years of follow up which may have remained otherwise undetected. Compliance
      with HRT appears to be comparable to that reported in other western specialist
      centres. Nearly 9% of women who stopped HRT did so because other doctors told
      them that they did need the treatment and another 6.5% because of the fear of
      breast cancer.

PMID- 9571597
TI  - Sensitive skin at menopause; dew point and electrometric properties of the
      stratum corneum.
AB  - OBJECTIVE: A number of menopausal women experience skin sensitive to various
      environmental threats. METHOD: Two panels of 15 menopausal women on or without
      HRT were compared. We studied the response of their stratum corneum to variations
      in environmental humidity, either in air or in response to an emollient.
      Environment dew point and electrometric measurements on the skin were recorded to
      search for correlations. RESULTS: Data show that the baseline stratum corneum
      hydration is influenced by the dew point. HRT improves the barrier function of
      the skin. The use of emollient further extends the improvement in the functional
      properties of skin in menopausal women. CONCLUSION: Both HRT and an emollient can
      counteract in part some of the deleterious effects of cold and dry weather.

PMID- 9571598
TI  - Effects of estrogen on susceptibility to oxidation of low-density and high
      density lipoprotein in postmenopausal women.
AB  - OBJECTIVE: To investigate the effects of estrogen on the susceptibility to
      oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in
      postmenopausal women. METHODS: A total of 23 postmenopausal women were treated
      with 0.625 mg of conjugated equine estrogen daily for 3 months. Blood samples
      were obtained before and after therapy. Plasma levels of total cholesterol and
      triglyceride and the concentrations of cholesterol, triglyceride, phospholipid in
      LDL and HDL were determined enzymatically and the levels of apolipoprotein A-I, A
      II in HDL and apolipoprotein B in LDL were measured by turbidimetric immunoassay.
      The isolated LDL and HDL were incubated at 37 degrees C for 24 h with CuSO4 5
      mumol/l and the lipid peroxide concentration of LDL and HDL was measured.
      RESULTS: Estrogen significantly reduced the plasma level of total cholesterol and
      significantly increased the plasma level of triglyceride. The LDL concentrations
      of cholesterol, phospholipid and apolipoprotein B were significantly decreased
      following estrogen therapy. The triglyceride level of LDL did not change
      significantly. The HDL concentrations of cholesterol, triglyceride, phospholipid
      and apolipoprotein A-I and A-II were all significantly elevated after estrogen
      therapy. Estrogen significantly inhibited the peroxidation of LDL at 50-2000
      micrograms of LDL protein (14.17 +/- 4.17-11.49 +/- 1.42 nmol/200 micrograms of
      LDL protein, P < 0.001) and of HDL (4.49 +/- 1.74-3.37 +/- 1.24 nmol/200
      micrograms of HDL protein, P < 0.03) induced by their incubation in the presence
      of CuSO4. CONCLUSIONS: Estrogen inhibited the susceptibility of LDL and HDL to
      oxidative modification and favorably affected lipid metabolism by reducing the
      number of LDL particles and increasing the number of HDL particles in plasma that
      were resistant to oxidation.

PMID- 9571599
TI  - Long-term effects of hormone replacement therapy on symptoms of angina pectoris,
      quality of life and compliance in women with coronary artery disease.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effects of HRT on
      symptoms of angina pectoris, quality of life and factors of importance for
      compliance in women with ischemic heart disease. METHODS: Sixty postmenopausal
      women with coronary artery disease were randomized into three groups: one group
      received transdermal 17 beta-estradiol at a dose of 50 micrograms per 24 h alone
      for 18 days followed by 10 days of combined treatment with medroxyprogesterone
      acetate (MPA) 5 mg orally; the second group received placebo and the third group
      received conjugated estrogens orally for 18 days followed by a combined treatment
      with MPA for 10 days. Clinical evaluations were performed at baseline, after 3, 6
      and 12 months. The investigations included gynecological history. occurrence of
      climacteric symptoms, quality of life evaluation, cardiac history and symptoms of
      angina pectoris. RESULTS: Forty-six women (77%) completed the study during 1
      year. The following cardiac events occurred in the women who completed the study:
      one patient was hospitalized because of congestive heart failure (patch), two
      patients because of angina pectoris, one patient because of coronary bypass
      operation (CEE) and three patients underwent balloon dilatation (placebo), all
      three on CEE. Among the 14 women who discontinued, two patients had TIA (patch),
      one experienced palpitations (CEE) and one woman died from myocardial infarction
      (placebo). Overall improvement in mood and cognitive functions were reported in
      all three treatment groups. CONCLUSIONS: HRT does not seem to have negative
      effects on symptoms of angina pectoris and seems to increase quality of life in
      older women with coronary heart disease. It also seems safe from the
      cardiovascular point of view.

PMID- 9571600
TI  - Long-term effects of percutaneous estradiol on bone loss and bone metabolism in
      postmenopausal hysterectomized women.
AB  - OBJECTIVE: To determine whether percutaneous estradiol (pE2) (1.5 mg/day) is able
      to counteract the postmenopausal bone loss in postmenopausal hysterectomized
      women, in a double-blind study versus oral estriol (E3) (2 mg/day). METHODS: The
      bone mineral density of the lumbar spine (LS) and of the proximal femur (PF) was
      measured every 3 months by dual energy X-ray absorptiometry for 2 years in 43
      hysterectomized postmenopausal women (21 in the E2 group and 22 in the E3 control
      group), and in a subset of patients for a 3rd year. The statistical analyses were
      performed on Macintosh using Stat View II. RESULTS: A significant bone loss of
      1.2 (0.4%)% and of 1.3 (0.3)% per year was observed in the control group,
      respectively at LS and at PF, versus a significant gain of 1.2 (0.5)% per year in
      the treated group at the LS. No significant change at PF occurred in the treated
      group. In the 20 patients followed up for a 3rd year on pE2, an increase of 1.2
      (0.9) and 2.5 (1.4)% at LS in the 12 former active group patients and the eight
      formerly control patients, respectively was seen. The same trend was observed at
      the proximal femur. CONCLUSION: pE2 (1.5 mg E2) is able to counteract the
      postmenopausal bone loss in hysterectomized women, whereas E3 (2 mg/day
      administered orally) is unable to maintain bone mass.

PMID- 9571601
TI  - Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal
      women.
AB  - OBJECTIVES: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels
      occurs in women during aging related to the reduction of adrenocortical
      secretion. A specific action of DHEA on the central nervous system (CNS) is
      suggested by the improvement of psychological and physical well-being in
      postmenopausal women after DHEA supplementation. The aim of the present study was
      to investigate the neuroendocrine effects of short-term DHEA supplementation in
      postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and
      growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in
      postmenopausal women (n = 6). METHODS: Before and after 7 days of DHEA
      supplementation, postmenopausal women underwent a neuroendocrine test with
      clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.).
      Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and
      estradiol (E2) levels were evaluated before and after treatment, while plasma
      beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after
      clonidine injection. RESULTS: Basal plasma beta-EP and GH levels did not show a
      significant difference before and after short-term DHEA administration, while
      circulating A, T, E1 and E2 significantly increased after treatment. The
      clonidine test induced a significant increase of plasma beta-EP levels in women
      after receiving DHEA supplementation but not before; conversely, plasma GM levels
      increased both before and after treatment. CONCLUSIONS: The present study
      indicates that short-term DHEA supplementation in postmenopausal women is able to
      restore the impaired response of pituitary beta-EP to clonidine, an alpha 2
      presinaptic agonist. According to these data it is possible to hypothesize that
      DHEA could play a role in the psychological and physical well-being of
      postmenopausal women acting via a restoration of neuroendocrine control of antero
      pituitary beta-EP secretion.

PMID- 9571602
TI  - Alterations in the insulin-like growth factor system during the menstrual cycle
      in normal women.
AB  - OBJECTIVES: To evaluate the effects of endogenous estrogens and progestins on the
      IGF-system during the normal menstrual cycle in healthy premenopausal women not
      using contraceptive drugs. METHODS: Nine women had fasting blood samples obtained
      at 2-3 days intervals during a 5 week study period. Plasma levels of IGF-I, IGF
      II, IGFBP-I, IGFBP-3, estradiol and progesterone were measured by
      radioimmunoassay (RIA) in each sample. IGFBP-3 was also evaluated by Western
      ligand blot (WLB) and immunoblot. Any differences between the menstrual phase
      (defined as day 1-5), follicular and luteal phases (separation based on plasma
      estradiol and progesterone values) were evaluated by the Friedman test. RESULTS:
      A small but significant difference in plasma levels of IGF-I (P < 0.01) and IGFBP
      d (P < 0.05) measured by RIA between the three phases were seen with the highest
      levels found during the follicular phase. No change in plasma levels of IGFBP-1
      and IGF-II was found and immunoblots did not reveal any alteration in the ratio
      of fragmented to intact IGFBP-3 during the menstrual cycle. A positive
      correlation between plasma levels of IGF-I and estradiol was seen in 8 out of 9
      patients (P = 0.012). CONCLUSIONS: The finding of a slight but significant higher
      level of plasma IGF-I in the follicular and luteal phases compared with the
      menstrual phase suggests plasma estradiol may influence the level of this growth
      factor. This hypothesis is further supported by the finding of a correlation
      between plasma levels of IGF-I and estradiol but not progesterone in individual
      patients at different times during the menstrual cycle.

PMID- 9571603
TI  - Cycle dependent variations in transfer of 133xenon from vagina to uterus in rats.
AB  - The possible existence of an oestrus cycle dependent on local transfer of
      133xenon from vagina to uterus was investigated in anaesthetized rats. 133Xenon
      in saline was infused into the vaginal lumen of rats in oestrous (n = 7) and
      dioestrous (n = 10). The uterus was removed 3 min after the infusion and the
      radioactivity in the organ counted, after which the remaining radioactivity in
      vagina was measured. The results showed that the radioactivity increased in all
      uteri compared with that of the background. The average transfer, expressed as
      per cent transfer, from vagina in the dioestrous group (5.5%) was significantly
      higher (P < 0.01, Mann-Whitney) than in the oestrous group (1.4%). The results
      suggest that the rate of transfer from vagina to uterus depended on the oestrous
      cycle. Vaginal treatment of women with progesterone for example, may similarly
      induce high local concentrations in the uterus. Empirically this is already used
      after in vitro fertilisation, it may also prevent progesterone induced migraine
      in menopausal women. The possible cycle dependent variations in the transfer in
      women should be evaluated.

PMID- 9571604
TI  - Metabolic effects of tibolone in postmenopausal women with non-insulin dependent
      diabetes mellitus.
AB  - OBJECTIVE: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are
      frequently obese, hypertensive and hyperlipidaemic and hence at particular risk
      of coronary heart disease (CHD). They might therefore benefit from menopausal
      therapy. In view of the improvement in insulin sensitivity and the reduction in
      triglyceride levels induced by tibolone in healthy postmenopausal women we
      evaluated the effects of 12 months of tibolone on glycaemic control, serum
      insulin and lipid levels in postmenopausal women with NIDDM. DESIGN: A
      prospective 12 months before/after intervention study. PATIENTS: Fourteen
      postmenopausal women (mean age 58.14 +/- 1.25 years; mean duration of menopause
      121.21 +/- 13.42 months; mean BMI: 26.55 +/- 0.97) with NIDDM (mean duration of
      diabetes 113.79 +/- 13.89 months). MEASUREMENTS: Fasting and postprandial blood
      glucose levels were assessed monthly, serum fructosamine, fasting and
      postprandial insulin every 3 months and serum lipids (total cholesterol,
      triglyceride, HDL-cholesterol and LDL-cholesterol) every 6 months. RESULTS:
      Changes in blood glucose, both fasting and postprandial, were not statistically
      significant during the treatment period. Serum fructosamine concentration
      increased significantly after 9 months. A significant decrease in fasting and
      postprandial insulin concentrations was observed after 9 months. A non
      significant decrease was observed in total cholesterol, LDL cholesterol and
      triglyceride but no change in HDL cholesterol. Body weight did not change during
      the period of observation. CONCLUSION: A slight deterioration in glycaemic
      control, a fall in insulin concentration and no change in serum lipids were
      observed in women with NIDDM during 12 months treatment with tibolone.

PMID- 9571605
TI  - High dose-rate brachytherapy treatment delivery: report of the AAPM Radiation
      Therapy Committee Task Group No. 59.
AB  - The goals of this task group are to examine the current high dose-rate (HDR)
      treatment delivery practices and to prepare a document to assure safe delivery of
      HDR treatments. The document consists of detailed HDR procedures for design of an
      HDR brachytherapy program, staffing and training, treatment specific quality
      assurance, and emergency procedures. The document provides an extensive quality
      assurance (QA) check list. It reviews all aspects of HDR treatment delivery
      safety, including prescription, treatment plan, treatment delivery, and radiation
      safety.

PMID- 9571606
TI  - A Monte Carlo study of verification imaging in high dose rate brachytherapy.
AB  - We have been evaluating the practicality of monitoring the position of an 192Ir
      source during high dose rate (HDR) brachytherapy treatments using x-ray
      fluoroscopy. The EGS4 Monte Carlo code has been used to simulate the interactions
      of 192Ir photons with the patient and the CsI phosphor of an x-ray image
      intensifier to predict what signals will be generated by these 192Ir photons. The
      calculations show that it is the 192Ir photons scattered within the patient that
      are mainly responsible for generating the spurious signals in the x-ray image
      intensifier that degrade image quality. The scattered 192Ir photons are
      distributed in the energy range (15-200 keV), which is markedly lower than the
      average energy of the primaries (360 keV), and therefore interact more
      efficiently with the CsI phosphor of the x-ray image intensifier. Experimental
      measurements support these observations, demonstrating that spurious signals
      produced by the 192Ir source become appreciably larger when the 192Ir source is
      located within a scattering object rather than air. For a 10 cm airgap, the
      signal-to-noise ratio (SNR) can decrease by factors ranging between 3 and 10 (no
      antiscatter grid), depending on the position of a 7 Ci 192Ir source inside a 30
      cm thick water phantom. In typical clinical situations, a focused grid (Pb, 12:1,
      40 lines/cm) can increase the SNR by about a factor of 2. Furthermore, the SNR
      rapidly increases with increasing airgap, such that a 20 cm airgap can be as
      effective as a 12:1 air interspaced grid in eliminating the spurious signals. Our
      results suggest that use of a high-current x-ray fluoroscopy technique, a large
      airgap, and a well-designed anti-scatter grid can make the fluoroscopic
      monitoring of source position in HDR brachytherapy feasible. This, in turn, can
      improve the quality assurance of such treatments.

PMID- 9571607
TI  - Monte Carlo dosimetry of the VariSource high dose rate 192Ir source.
AB  - The purpose of the work is to calculate basic dosimetry data for a VariSource
      high dose rate 192Ir source in water. These basic dosimetry data, expressed in
      the dose calculation formalism endorsed by the Interstitial Collaborative Working
      Group and AAPM Task group 43, include the dose rate constant, the radial dose
      function, and the anisotropy function. A modified version of the EGS4 Monte Carlo
      code was used to calculate (1) the transverse-axis dose distribution at radial
      distances from 0.1 to 14 cm, (2) the two-dimensional dose distribution for axial
      and radial distances from 0.1 cm to 10 cm, and (3) the air-kerma strength, for
      the VariSource high dose rate 192Ir source. From these Monte Carlo results the
      basic dosimetry data were derived. The calculated dose rate constant for the high
      dose rate source is 1.044 +/- 0.2% cGy h-1 per unit air-kerma strength. The
      anisotropy function exhibits 40%-60% deviations from isotropy at positions on the
      long axis. The radial dose function for the source is nearly identical to that
      for a microSelectron high dose rate 192Ir source, except at radial distances
      smaller than 0.5 cm where values for VariSource are 1.7%-2.8% smaller. These
      basic dosimetry data were compared with corresponding results from other authors
      for high and low dose rate 192Ir sources, as well as with Meisberger's fitting
      formula.

PMID- 9571608
TI  - Dosimetric verification of the 95% isodose surface for a conformal irradiation
      technique.
AB  - In the treatment planning of conformal radiotherapy, field shapes are often
      designed in such a way that a high-value isodose surface fully encompasses the
      target volume. Therefore, knowledge about the accuracy with which the treatment
      planning system calculates the position of that isodose surface is essential to
      prevent field shapes which are either too large or too small. To determine this
      accuracy for a conformal multi-field technique, the dose in the high-dose region
      must be measured with a high spatial resolution. A method is presented to
      reconstruct and evaluate the experimental high-dose region from a set of water
      phantom scans. This method, which assesses combined dose profiles for multi-field
      irradiation techniques, can be used for the commissioning and/or quality
      assurance of a 3-D treatment planning system. For a specific conformal technique,
      the measured and calculated 95% isodose positions along lines in several
      directions have been compared. It is shown that different dose values of single
      beam profiles determine the resulting 95% isodose position, which is important to
      recognize for quality assurance of treatment planning calculations. It is further
      found that the uncertainty in the calculated 95% isodose surface can be described
      by a standard deviation in dose value, which relates to a positional uncertainty
      through the local dose gradient. Thus the confidence region of the calculated 95%
      isodose can be indicated in the treatment plan by plotting isodoses at the 95%
      level plus and minus its standard deviation. Such a procedure is recommended
      instead of plotting the 95% isodose with a constant width. In addition,
      restrictions for the cumulative dose-volume histogram of acceptable treatment
      plans can be formulated, based on the sensitivity of the actual target coverage
      on the uncertainty with which the prescribed isodose surface is calculated.

PMID- 9571609
TI  - Optimization of intensity modulated beams with volume constraints using two
      methods: cost function minimization and projections onto convex sets.
AB  - For accurate prediction of normal tissue tolerance, it is important that the
      volumetric information of dose distribution be considered. However, in dosimetric
      optimization of intensity modulated beams, the dose-volume factor is usually
      neglected. In this paper we describe two methods of volume-dependent optimization
      for intensity modulated beams such as those generated by computer-controlled
      multileaf collimators. The first method uses a volume sensitive penalty function
      in which fast simulated annealing is used for cost function minimization (CFM).
      The second technique is based on the theory of projections onto convex sets
      (POCS) in which the dose-volume constraint is replaced by a limit on integral
      dose. The ability of the methods to respect the dose-volume relationship was
      demonstrated by using a prostate example involving partial volume constraints to
      the bladder and the rectum. The volume sensitive penalty function used in the CFM
      method can be easily adopted by existing optimization programs. The convex
      projection method can find solutions in much shorter time with minimal user
      interaction.

PMID- 9571610
TI  - Sensitivity of amorphous selenium to x rays from 40 kVp to 18 MV: measurements
      and implications for portal imaging.
AB  - Recently, the clinical application of electronic portal imaging devices has
      enabled more frequent verification of patient setup for radiation treatment.
      However, the image quality has sometimes proven to be inadequate, motivating the
      investigation of alternative sensors with better image quality. Amorphous
      selenium (a-Se) is potentially one such sensor since the electrostatic image
      formation process has high resolution. To fully evaluate the potential of a-Se
      for portal imaging, it is necessary to investigate all the imaging properties at
      high x-ray energies. Here, measurements of the sensitivity of a-Se to incident x
      ray spectra ranging in energy from 40 kVp to 18 MV and for a-Se thicknesses
      ranging from approximately 10 to 300 microns under full buildup conditions are
      described. When x rays or energetic electrons deposit energy in a photoconductor
      with an applied electric field, F, electrons and holes are released. The x-ray
      conversion sensitivity may be defined as 1/W +/-, where W +/- is the energy
      required to release an electron-hole pair. Consistent with the results of
      previous investigators, W +/- is found to vary approximately with F-2/3.
      Unexpectedly, over the energy range of 40 kVp to 18 MV, W +/- was found to
      decrease by a factor of nearly 3. These dependencies are compared to the
      predictions of two competing charge recombination models, geminate and columnar.
      The results are explained by a microdosimetric model in which the sensitivity at
      megavoltage energies is governed by geminate recombination, but at lower
      energies, both mechanisms are involved. Thus, the sensitivity of a-Se to x rays
      spanning the diagnostic and radiotherapy range has been measured and the physical
      basis for this behavior established.

PMID- 9571611
TI  - A technique for calculating range spectra of charged particle beams distal to
      thick inhomogeneities.
AB  - A method was developed for calculating range spectra of charged particles after
      passing through an inhomogeneous structure whose thickness was comparable to the
      range of the incident particles. It was shown that the spectra are strongly
      affected by the influence of multiple Coulomb scattering at interfaces parallel
      to the beam direction of two media with different relative stopping power. The
      calculations are in agreement with Monte Carlo simulations. The degraded Bragg
      peak was calculated on the basis of the computed range spectra behind the
      inhomogeneity interface. The method can be included into charged particle
      treatment planning systems where broad pencil beams are used to predict the
      deteriorated Bragg peak behind inhomogeneity interfaces more precisely.

PMID- 9571612
TI  - Fast 2D phantom dosimetry for scanning proton beams.
AB  - A quality control system especially designed for dosimetry in scanning proton
      beams has been designed and tested. The system consists of a scintillating screen
      (Gd2O2S:Tb), mounted at the beam-exit side of a phantom, and observed by a low
      noise CCD camera with a long integration time. The purpose of the instrument is
      to make a fast and accurate two-dimensional image of the dose distribution at the
      screen position in the phantom. The linearity of the signal with the dose, the
      noise in the signal, the influence of the ionization density on the signal, and
      the influence of the field size on the signal have been investigated. The spatial
      resolution is 1.3 mm (1 s.d.), which is sufficiently smaller than typical
      penumbras in dose distributions. The measured yield depends linearly on the dose
      and agrees within 5% with the calculations. In the images a signal to noise
      ration (signal/1 s.d.) of 10(2) has been found, which is in the same order of
      magnitude as expected from the calculations. At locations in the dose
      distribution possessing a strong contribution of high ionization densities (i.e.,
      in the Bragg peak), we found some quenching of the light output, which can be
      described well by existing models if the beam characteristics are known. For
      clinically used beam characteristics such as a Spread Out Bragg peak, there is at
      most 8% deviation from the NACP ionization chamber measurements. The conclusion
      is that this instrument is a useful tool for quick and reliable quality control
      of proton beams. The long integration-time capabilities of the system make it
      worthwhile to investigate its applicability in scanning proton beams and other
      dynamic treatment modalities.

PMID- 9571613
TI  - A proton dose calculation algorithm for conformal therapy simulations based on
      Moliere's theory of lateral deflections.
AB  - An algorithm is developed for computing proton dose distributions in the
      therapeutic energy range (100-250 MeV). The goal is to provide accurate pencil
      beam dose distributions for two-dimensional or three-dimensional simulations of
      possible intensity-modulated proton therapy delivery schemes. The algorithm is
      based on Moliere's theory of lateral deflections, which accurately describes the
      distribution of lateral deflections suffered by incident charged particles. The
      theory is applied to nonuniform targets through the usual pencil beam
      approximation which assumes that all protons from a given pencil beam pass
      through the same material at each depth. Fluence-to-dose conversion is made via
      Monte Carlo calculated broad-field central-axis depth-dose curves, which accounts
      for attenuation due to nuclear collisions and range straggling. Calculation speed
      is enhanced by using a best-fit Gaussian approximation of the radial distribution
      function at depth. Representative pencil beam and spread-out Bragg-peak
      computations are presented at 250 MeV and 160 MeV in water. Computed lateral full
      widths-at-half-maximum's in water, at the Bragg peak, agree with the expected
      theoretical lateral values to within 1% at 160 MeV and to within 3% at 250 MeV.
      This algorithm differs from convolution methods in that the effect of the depth
      of any inhomogeneities in density or atomic composition are accounted for in a
      rigorous fashion. The algorithm differs from Fermi-Eyges based methods by
      accounting in a rigorous way for the effect of nonsmall-angle scattering and
      screening due to atomic electrons. The computational burden is only slightly
      greater than that expected using the less-rigorous Fermi-Eyges theory.

PMID- 9571614
TI  - Attenuation characteristics of a new compensator material: Thermo-Shield for high
      energy electron and photon beams.
AB  - A new thermoplastic material with extremely desirable physical and radiation
      shielding properties is presented. The material softens between 108 degrees F and
      132 degrees F and can then be easily molded to any desired shape. As it cools
      down it hardens at about 102 degrees F, retaining its molded shape. It is very
      light (rho = 1.66 g/cc), compared to most other compensating and shielding
      materials used in the clinic. Its photon and electron attenuation characteristics
      have been measured and are compared with other materials relevant to
      radiotherapy. Possible applications as a bolus material, compensator and partial
      or total shielding material in clinical radiation therapy are discussed.

PMID- 9571615
TI  - Production of radioisotopes by direct electron activation.
AB  - High-energy electrons bombarded on materials can induce radioactivity by either
      directly knocking out neutrons or by first converting a fraction of the electron
      kinetic energy into electromagnetic energy, with subsequent neutron emission
      induced by the photons produced. The purpose of this paper was to develop a
      calculation method for estimating neutron emission and radionuclide production by
      high-energy (15-25 MeV) electrons directly interacting with a nucleus. The
      reaction (e,n) is considered using the method of virtual photons. The cross
      section for electron bombardment of lead, tantalum, rhenium, and tungsten targets
      is calculated. The electron cross sections are roughly 100 times less than the
      corresponding photon cross sections. The cross section increases monotonically
      with incident energy. A traveling wave linear accelerator was used for a
      qualitative test of the magnitude and energy dependence of the calculated cross
      sections. Tantalum was bombarded with electrons and the resultant emission of
      neutrons was inferred from the induced activation of 180Ta. The energy dependence
      and magnitude of the calculated electron cross sections agree with experiment
      within experimental uncertainties. It is concluded that accurate estimates of
      electron activation via the direct process is possible.

PMID- 9571616
TI  - Startup performance of the traveling wave versus standing wave linear
      accelerator.
AB  - The startup performance of medical linear accelerators is of increasing
      importance for modern radiotherapy techniques. The traveling wave-type linear
      accelerator of the SL series of Philips (now Elekta Oncology Systems) has been
      modified in its flight tube design to meet this goal of a fast rise time of the
      radiation field. The new slitless flight tube combined with a redesigned gun
      servo electronic now achieves start up times of the radiation comparable with
      those of a standing wave linear accelerator (Siemens Mevatron) according to our
      measurements.

PMID- 9571617
TI  - Equilibration of air temperature inside the thimble of a Farmer-type ion chamber.
AB  - Ionization chambers are frequently moved from one environment to another,
      sometimes with significant differences in temperature between the chamber and
      measurement phantom. To obtain reliable ionization data, the temperature of the
      air in the chamber must be allowed to equilibrate with the measuring phantom. The
      air temperature inside a thimble of a Farmer-type ion chamber was measured as a
      function of time for various phantom materials (air, water, and plastic).
      Equilibration rates for the various conditions are presented. Heat-diffusion
      theory is presented to explain the characteristics of the measured data. Waiting
      times for temperature equilibration down to 10% of the initial temperature
      difference ranges from 1 to 18 min, depending on the phantom material and use of
      bare or covered thimble. Radiation measurements confirm the temperature data.

PMID- 9571618
TI  - Use of a new type of radiochromic film, a new parallel-plate micro-chamber,
      MOSFETs, and TLD 800 microcubes in the dosimetry of small beams.
AB  - The dosimetry of the fields usually employed in radiosurgery requires the use of
      small detectors to measure Total Scatter Factor (Sc,p), Tissue Maximum Ratio
      (TMR), Percentage Depth Dose (PDD), and Off Axis Ratio (OAR). In this paper new
      dosimeters are investigated: a new type of radiochromic film, a micro parallel
      plate chamber (filled with both air and tetramethylsilane, TMS), MOSFETs, and TLD
      800 microcubes. Their behavior has been compared with the response of
      radiographic film and with the values obtained with BEAM Monte Carlo simulation.
      The experimental data confirm that dosimetry with radiochromic films and TLDs
      gives consistent results for all beam diameters. The parallel-plate micro chamber
      underestimates the Sc,p for the smallest field diameters (4.4 mm and 6.7 mm);
      MOSFETs show an over-estimation for the Sc,p of the 4.4 mm, 6.7 mm, and 10.5 mm
      field diameters. BEAM Monte Carlo simulation employing a parallel beam and a
      standard 6 MV x-ray spectrum has been used to obtain a correction factor as a
      function of the field size for both the parallel-plate micro chamber and MOSFETs.
      High accuracy measurements of PDD and TMR have been made in a water phantom both
      with radiochromic film and with the micro parallel-plate chamber and have been
      compared with the data computed by BEAM Monte Carlo simulation. The latter
      dosimeter is preferred because of the quicker and simpler use and because it
      gives immediate readout. Measurements of OAR made with radiochromic films and
      with radiographic films give differences in the 80%-20% penumbra width within 0.6
      mm for field diameters ranging from 4.4 mm to 19 mm.

PMID- 9571619
TI  - Measurement of the neutron sensitivity of TLD-300 irradiated in a tissue
      equivalent phantom by d(48.5) + Be neutrons.
AB  - The neutron sensitivities of the total response (kT) as well as of separate peaks
      3 (k3) and 5 (k5) on the glow curve were measured for CaF2:Tm (TLD-300)
      thermoluminescent dosimeters. The TLD-300 were encapsulated in A-150 TE plastic
      and located at different depths in the water phantom. The phantom was irradiated
      with neutrons produced by the d(48.5) + Be reaction at the superconducting
      cyclotron of the Gershenson Radiation Oncology Center at Harper Hospital. A set
      of measurements, based on the use of a TE ionization chamber and Geiger-Muller
      (GM) counter was used to measure the neutron (Dn) and gamma (D gamma) dose at
      these locations. The neutron sensitivities of the TLDs were thus derived by
      comparison with the results obtained with the twin detector method. The average
      neutron sensitivities relative to gamma of the total response and the responses
      of single peaks 3 or 5 are 0.215 +/- 0.016, 0.126 +/- 0.010, and 0.357 +/- 0.014,
      respectively. A linear relationship was found between the ratio of the areas
      under peak 3 to that under peak 5 and the ratio of the gamma dose to the total
      dose.

PMID- 9571620
TI  - Computerized characterization of masses on mammograms: the rubber band
      straightening transform and texture analysis.
AB  - A new rubber band straightening transform (RBST) is introduced for
      characterization of mammographic masses as malignant or benign. The RBST
      transforms a band of pixels surrounding a segmented mass onto the Cartesian plane
      (the RBST image). The border of a mammographic mass appears approximately as a
      horizontal line, and possible speculations resemble vertical lines in the RBST
      image. In this study, the effectiveness of a set of directional textures
      extracted from the images before the RBST. A database of 168 mammograms
      containing biopsy-proven malignant and benign breast masses was digitized at a
      pixel size of 100 microns x 100 microns. Regions of interest (ROIs) containing
      the biopsied mass were extracted from each mammogram by an experienced
      radiologist. A clustering algorithm was employed for automated segmentation of
      each ROI into a mass object and background tissue. Texture features extracted
      from spatial gray-level dependence matrices and run-length statistics matrices
      were evaluated for three different regions and representations: (i) the entire
      ROI; (ii) a band of pixels surrounding the segmented mass object in the ROI; and
      (iii) the RBST image. Linear discriminant analysis was used for classification,
      and receiver operating characteristic (ROC) analysis was used to evaluate the
      classification accuracy. Using the ROC curves as the performance measure,
      features extracted from the RBST images were found to be significantly more
      effective than those extracted from the original images. Features extracted from
      the RBST images yielded an area (Az) of 0.94 under the ROC curve for
      classification of mammographic masses as malignant and benign.

PMID- 9571621
TI  - Digital radiology using active matrix readout of amorphous selenium: radiation
      hardness of cadmium selenide thin film transistors.
AB  - A flat-panel x-ray imaging detector using active matrix readout of amorphous
      selenium (a-Se) is being investigated for digital radiography and fluoroscopy.
      The active matrix consists of a two-dimensional array of thin film transistors
      (TFTs). Radiation penetrating through the a-Se layer will interact with the TFTs
      and it is important to ensure that radiation induced changes will not affect the
      operation of the x-ray imaging detector. The methodology of the present work is
      to investigate the effects of radiation on the characteristic curves of the TFTs
      using individual TFT samples made with cadmium selenide (CdSe) semiconductor.
      Four characteristic parameters, i.e., threshold voltage, subthreshold swing,
      field effect mobility, and leakage current, were examined. This choice of
      parameters was based on the well established radiation damage mechanisms for
      crystalline silicon metal-oxide-semiconductor field-effect transistors (MOSFETs),
      which have a similar principle of operation as CdSe TFTs. It was found that
      radiation had no measurable effect on the leakage current and the field effect
      mobility. However, radiation shifted the threshold voltage and increased the
      subthreshold swing. But even the estimated lifetime dose (50 Gy) of a diagnostic
      radiation detector will not affect the normal operation of an active matrix x-ray
      detector made with CdSe TFTs. The mechanisms of the effects of radiation will be
      discussed and compared with those for MOSFETs and hydrogenated amorphous silicon
      (a-Si:H) TFTs.

PMID- 9571623
TI  - Algorithm for image reconstruction in multi-slice helical CT.
AB  - Efforts are being made to develop a new type of CT system that can scan volumes
      over a large range within a short time with thin slice images. One of the most
      promising approaches is the combination of helical scanning with multi-slice CT,
      which involves several detector arrays stacked in the z direction. However, the
      algorithm for image reconstruction remains one of the biggest problems in multi
      slice CT. Two helical interpolation methods for single-slice CT, 360LI and 180LI,
      were used a starting points and extended to multi-slice CT. The extended methods,
      however, had a serious image quality problem due to the following three reasons:
      (1) excessively close slice positions of the complementary and direct data,
      resulting in a larger sampling interval; (2) the existence of several
      discontinuous changeovers in pairs of data samples for interpolation; and (3) the
      existence of cone angles. Therefore we have proposed a new algorithm to overcome
      the problem. It consists of the following three parts: (1) optimized sampling
      scan; (2) filter interpolation; and (3) fan-beam reconstruction. Optimized
      sampling scan refers to a special type of multi-slice helical scan developed to
      shift the slice position of complementary data and to acquire data with a much
      smaller sampling interval in the z direction. Filter interpolation refers to a
      filtering process performed in the z direction using several data. The normal fan
      beam reconstruction technique is used. The section sensitivity profile (SSP) and
      image quality for four-array multi-slice CT were investigated by computer
      simulations. Combinations of three types of optimized sampling scan and various
      filter widths were used. The algorithm enables us to achieve acceptable image
      quality and spatial resolution at a scanning speed that is about three times
      faster than that for single-slice CT. The noise characteristics show that the
      proposed algorithm efficiently utilizes the data collected with optimized
      sampling scan. The new algorithm allows suitable combinations of scan and filter
      parameters to be selected to meet the purpose of each examination.

PMID- 9571622
TI  - Digital radiology using active matrix readout of amorphous selenium: detectors
      with high voltage protection.
AB  - A flat-panel x-ray imaging detector is being investigated for digital radiography
      and fluoroscopy. The detector uses a layer of amorphous selenium (a-Se) to
      convert x rays to a charge image, which is then electronically read out with a
      two-dimensional array of thin film transistors (TFTs). In order to sensitize the
      a-Se layer to x rays, a high voltage (of the order of several thousand volts) is
      applied to its top surface. The TFTs, which are at the bottom surface of the a-Se
      layer, are not subjected to any high voltage under normal radiological
      operational conditions since the pixel potential is < 10 V. However under a fault
      condition where these two events occur simultaneously: (1) suspended detector
      scan; and (2) an x-ray exposure more than ten times higher than normal, the
      voltage on the TFTs could rise to a damaging value. This paper describes a method
      for protecting the TFTs from high voltage damage under this fault condition. It
      employs a dual-gate TFT structure, one gate is for scanning control and the other
      is connected to the pixel electrode for high voltage protection. Before the pixel
      potential reaches a damaging value, the protection gate turns on the TFT
      automatically and drains excess charge away from the pixel thus providing a safe
      pixel saturation potential. In this paper, the characteristic curves of dual-gate
      TFTs are studied both theoretically and experimentally. The pixel x-ray response
      for imaging detectors with high voltage protection are predicted, and it is shown
      that with practical TFT designs the detector can provide a safe pixel saturation
      potential as well as satisfy the dynamic range required for diagnostic x-ray
      imaging applications.

PMID- 9571624
TI  - A general approach for multidimensional smoothing.
AB  - Smoothing is closely related to regression in statistics. It is frequently
      applied to data that contain statistical noise in attempts to discern and
      highlight patterns concealed in the data. In medical imaging applications, the
      acquired data are often N dimensional (where N > or = 2) and thus
      multidimensional smoothing approaches would best exploit the multidimensional
      correlations inherent in the data. Unfortunately, extensions of advanced
      (especially adaptive) one-dimensional smoothing approaches to multidimensional
      data are, in general, theoretically challenging and computationally prohibitive.
      In this work, we propose a novel approach that accomplishes effectively higher
      dimensional smoothing by exploiting the Fourier transform properties of the data
      to reduce data dimensions, allowing for lower-dimensional smoothing. We present
      the theoretical basis for this approach and verify this approach by applying it
      to computer-simulated data as well as real data acquired in medical imaging
      studies.

PMID- 9571625
TI  - The "VH1-like" dual-specificity protein tyrosine phosphatases.
AB  - The number of dual-specificity protein tyrosine phosphatases has grown
      considerably in the last few years, and thus it would be helpful to organize
      these novel enzymes. The simple term "VH1-like" or "dual-specificity" phosphatase
      does not adequately reflect the different subclasses within this new and
      important phosphatase subfamily. In this article, we review the salient features
      of dual-specificity phosphatases and propose a novel classification scheme of
      these enzymes based on their structural motifs. Classification of dual
      specificity phosphatases based on their motifs should serve as a useful
      organizational framework for bringing together this now large subgroup of
      phosphatases. Moreover, this classification scheme may hold predictive value,
      since some of these motifs may hold the key to new, undiscovered functional
      properties.

PMID- 9571626
TI  - Linkage disequilibrium of the Apo AI-CIII-AIV gene cluster and their relationship
      to plasma triglyceride, apolipoprotein AI and CIII levels in Koreans.
AB  - More than 20 different RFLPs have been described in the apo AI-CIII-AVI gene
      cluster and their association with several dyslipidemias has been claimed in
      different populations. So far, however, the results of their association have
      been largely inconclusive. We analyzed six previously described RFLPs (Paul
      Hayase et al., 1992) in the apo AI-CII-AIV gene cluster by using PCR-amplified
      DNAs in 132 healthy subjects to document the relationship between the RFLPs and
      dyslipoproteinemias. The polymorphic sites were located in the promoter region of
      the apo AI gene (G to A substitution, MspI), in the 3' flanking region of the apo
      AI gene (PstI), in the 3' noncoding region of the apo CIII gene (SstI), in the
      first intron of the apo CIII gene (PvuIIa), in the intergenic region of the apo
      CIII and apo AIV genes (PvuIIb), and in the second intron of the apo AIV gene
      (XbaI), respectively. The allele frequencies of PstI polymorphism showed no
      ethnic difference. However, in G to A substitution sites (MspI), Koreans had a
      lower G allele frequency than that of Caucasians. Among Oriental ethnic groups
      there were no significant differences in the allele frequencies of SstI and
      PvuIIa RFLPs, whereas significant differences existed between individuals of
      Oriental, Caucasian, and/or African origins. Koreans were monomorphic for PvuIIb
      and XbaI restriction sites. Pairwise linkage disequilibrium analysis revealed two
      pairs of significant negative linkage disequilibriums (MspI-SstI and SstI
      PvuIIa). Although there were no statistical significances, the S2 allele of SstI
      polymorphism and the G allele of MspI polymorphism seemed to be associated with
      hypertriglyceridemia. Thus linkage of the G allele of MspI polymorphism and the
      S2 allele of SstI polymorphism could give an additive effect on an increment of
      triglyceride levels. We did not find any association between the SstI
      polymorphism and apo CIII levels. In conclusion, there were no statistically
      significant relationships detected between the apo AI-CIII-AVI gene cluster
      polymorphisms and the levels of various lipid parameters.

PMID- 9571627
TI  - Cloning of a cDNA encoding phospholipase D from Pimpinella brachycarpa.
AB  - Phospholipase D (PLD, EC 3.1.4.4) has been known to be related to various
      cellular processes in plants. To gain an understanding of the property of the
      enzyme in Pimpinella brachycarpa, the cDNA of the enzyme was isolated by PCR with
      degenerate primers, cDNA library screening, and 5' RACE. The full-length PLD cDNA
      is 2859 bp long and contains an open reading frame of 2424 bp coding for a
      polypeptide of 808 amino acids. The deduced enzyme has a calculated molecular
      mass of 91.7 kDa and pI of 5.86. The percent identity and similarity values of P.
      brachycarpa PLD with those of other PLDs in plants are 70 approximately 78 and 84
      approximately 95, respectively. It was identified that PLD from P. brachycarpa
      has HQKIVVVD and HAKMMIVD sequences which were homologous with a duplicated
      HXKXXXXD motif that has been conserved in PLDs from plants, animals, and yeast.
      Based on the analysis of amino acid similarity, it is believed that PLD from P.
      brachycarpa is an alpha form which is distinct from PLD beta reported recently.
      The N-terminus is homologous to the C2 domain which is present in a number of
      different proteins involved in signal transduction and membrane trafficking in
      animals. Southern and northern blot analyses indicated that PLD was expressed
      from one copy of PLD gene in the genome of P. brachycarpa.

PMID- 9571628
TI  - Cloning and sequencing of the celA gene encoding CMCase of Erwinia carotovora
      subsp. carotovora LY34.
AB  - The phytopathogenic Erwinia carotovora subsp. carotovora LY34 secretes multiple
      isozymes of the plant cell wall-disintegrating enzyme, endoglucanases. Genomic
      DNA from Ecc LY34 was digested with Sau3AI and ligated into the BamHI site of
      pBluescript II SK+. One of the E. coli clones containing a Sau3AI fragment of Ecc
      genomic DNA hydrolyzed carboxymethyl cellulose and was shown to contain the 2.2
      kb BamHI restriction fragment, which was subcloned to generate pLYCA100 named as
      celA. The structural organization of a celA gene encoding 387 amino acids
      consists of an open reading frame (ORF) of 1161 bp starting with an ATG start
      codon and followed by a TAA stop codon. CelA protein contained a typical
      catalytic domain, interdomain, cellulose binding domain, and prokaryotic signal
      peptide of 32 amino acids. Since the deduced amino acid sequences of CelA protein
      was very similar to those of CelV of Erwinia carotovora subsp. carotovora SCC3193
      enzyme and to those of CelN of Erwinia atroceptica enzyme, it belongs to the
      cellulase family 5. The apparent molecular mass of CelA protein was calculated to
      be 39 kDa by carboxymethylcellulose-sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (CMC-SDS-PAGE). Activity staining of carboxymethyl cellulase
      (CMCase) in sodium dodecyl sulfate polyacrylamide gel containing 0.1% CMC
      revealed that the cloned isozyme comigrated with a corresponding isozyme produced
      by Ecc LY34. The CelA had a calculated pI of 5.42. The optimum pH was 7 and the
      optimum temperature was about 45 degrees C.

PMID- 9571629
TI  - Production of high-titer retroviral vectors and detection of replication
      competent retroviruses.
AB  - Retroviral infection or calcium phosphate-mediated DNA transfection has been used
      for the generation of retrovirus producing cell lines through the introduction of
      vector DNA into the chromosomes of packaging cells. To compare the ability of the
      methods for DNA delivery to produce high-titer virus, we generated stable
      retroviral vector producing cell lines by the transfection or infection of a LN
      based vector DNA into PA317 cells and assayed individual clones for production of
      virus. Of eight randomly chosen G418-resistant clones generated by transfection,
      only one clone produced the vector at up to > 10(7) cfu/ml. Two of the five
      clones generated by infection yielded higher-titer viruses in the absence of
      helper virus--up to 5 x 10(7) more than the transfected clones. The titer of
      retroviral vectors can be increased by multiple rounds of infection through long
      term incubation of amphotropic virus producing cells with ecotropic virus
      vectors. Such amplification of vector copy number resulted in increase in vector
      titer of up to 20-fold. For the experiments presented here, we have used an
      improved vector/packaging system designed for minimizing the possibilities for
      the generation of an replication-competent retrovirus (RCR). However, the
      potential of RCR generation was detected in the culture medium harvested from the
      highest-titer virus producing PA317 clonal cells generated by amplification of
      the vector through the modified cocultivation technique, although the generation
      of RCR is very infrequent in the system.

PMID- 9571630
TI  - Characterization of protein interaction among subunits of protein kinase CKII in
      vivo and in vitro.
AB  - Protein kinase CKII (CKII) is a ubiquitous protein serine/threonine kinase. CKII
      usually exists in tetrameric complexes composed of two catalytic (CKII alpha
      and/or CKII alpha') and two regulatory (CKII beta) subunits. In the present
      study, using a combined in vivo and in vitro approach, we have investigated the
      role of CKII subunits in the formation of the tetrameric structure of CKII and
      the formation of the polymeric structure of CKII holoenzyme. Our in vivo
      experiments show that CKII beta interacts with either another CKII beta or CKII
      alpha and that CKII alpha does not interact with another CKII alpha (or CKII
      alpha'). Our in vitro experiments also show that CKII beta is able to associate
      with both CKII alpha and another CKII beta and that CKII alpha exists as a
      monomeric form in solution. These data indicate that CKII beta mediates the
      formation of a tetramer by both the dimerization of CKII beta and the interaction
      of CKII beta with CKII alpha. The results of this study also suggest that CKII
      beta may be involved in the formation of the polymeric structure of the CKII
      holoenzyme.

PMID- 9571631
TI  - The role of inverted repeat (IR) sequence of the virE gene expression in
      Agrobacterium tumefaciens pTiA6.
AB  - Agrobacterium tumefaciens pTiA6 virE promoter has a vir box, an inverted repeat
      (IR) sequence, a putative -35 region and a consensus -10 region. To study how the
      IR sequence of the virE promoter plays a role in virE gene expression, various
      mutants were constructed by base substitution and deletion in the virE promoter
      region. Substitution of the 3'-end region of the IR sequence, 5'-TCCGTTTCAA-3' to
      5'-GCGGCCGCTC-3' displayed 2.6% of the native virE promoter activity. A deletion
      mutant of 5'-CGTTTCAA-3' on the 3'-end region of the IR sequence expressed 6% of
      the native virE promoter activity. These mutational analyses demonstrated that
      the IR sequence of the virE promoter plays a role as a cis-acting element in virE
      expression.

PMID- 9571632
TI  - Generation of the short RNA transcript in Leishmaniavirus correlates with the
      growth of its parasite host, Leishmania.
AB  - Leishmaniavirus 1 is a double-stranded RNA virus that infects the New World
      kinetoplastid parasites, Leishmania braziliensis, and Leishmania guyanensis. The
      isolated virus particles contain an RNA-dependent RNA polymerase which exhibits
      both transcriptase activity for genome-length plus-strand synthesis and replicase
      activity for genome-length minus-strand synthesis. Recently, we identified a 320
      nucleotide short RNA transcript of Leishmaniavirus 1-4, derived from the 5' end
      of the viral plus-strand, which is generated by the virus capsid via site
      specific cleavage of the full-length positive single-stranded RNA. We have
      hypothesized that this short RNA transcript functions to regulate the virus life
      cycle during the growth of its parasite host, Leishmania guyanensis. To address
      this hypothesis, we measured the relative amount of short RNA transcripts and the
      absolute number of viral genomes per infected cell from log through stationary
      phase of the parasite growth cycle. In vitro assays of the viral polymerase
      showed an overall increase in viral polymerase activity from log growth into
      stationary phase which mirrored an in vivo increase in the quantity of double
      stranded genome as measured by agarose gel electrophoresis. We have developed
      competitive reverse transcription-polymerase chain reaction (RT-PCR) assays to
      measure the relative amounts of viral transcripts in infected cells as well as
      the number of viral genomes per infected cell. The results of these assays show
      that the amount of full-length virus transcripts peaks in the parasite stationary
      phase (132 transcripts per cell), and that the short transcript is most abundant
      in the early stationary phase cells (24 transcripts per cell).

PMID- 9571634
TI  - Characterization and intracellular localization of the Rok1 protein involved in
      yeast cell division.
AB  - The ROK1 gene is essential for the cell cycle progression in Saccharomyces
      cerevisiae. ROK1 has been predicted to encode an ATP-dependent RNA helicase of
      the DEAD-box family. We have analyzed the ROK1 gene expression both at the
      protein and RNA levels. Polyclonal antibodies were raised against trpE::rok1
      hybrid proteins and were affinity purified by using lacZ::rok1 hybrid proteins.
      Western blot experiments using anti-Rok1 antibodies revealed a single protein
      band of 64 kDa which is an expected size from the Rok1 amino acid sequence.
      Indirect immuno-fluorescence showed that the Rok1 protein is localized
      predominantly to the cytoplasm of the vegetatively growing cells. We have
      detected immunocross-reactive homologs of Rok1p in Candida albicans and
      Drosophila melanogaster.

PMID- 9571633
TI  - Cloning of genes specifically expressed in rice embryogenic cells.
AB  - We have examined differences in gene expression pattern between embryogenic
      callus (EC) and nonembryogenic callus (NEC) derived from mature seed embryo of
      rice (Oryza sativa L. cv Donggin). Three EC-specific transcripts were identified
      by differential display of amplified cDNAs. Specific expression of two partial
      cDNAs, designated as REC1 and REC2, respectively, was confirmed by a northern
      blot analysis. Partial nucleotide sequence of the clone REC1 showed no homology
      with any known genes, but partial amino acid sequence deduced from the clone REC2
      exhibited 55-82% homology with nickel-cobalt-resistant proteins identified from a
      bacterium, Alcaligenes eutrophus CH34.

PMID- 9571635
TI  - Molecular phylogeny of arthropods and their relatives: polyphyletic origin of
      arthropodization.
AB  - Because the enigmatic arthropod relatives, such as tardigrades, onychophorans,
      pentastomids, and pycnogonids, have features characteristic of not only both
      major arthropod groups but also several other animal phyla, analysis of their
      phylogenetic positions may provide important clues for metazoan phylogeny in
      general. From analyses of complete or nearly complete 18S rDNA sequences,
      arthropod monophyly including all the traditional arthropod relatives was well
      supported. For detailed analyses within arthropods without outgroup effects, we
      made two reduced alignments. From the analyses of these reduced data sets,
      arthropods were divided into two clades: one was chelicerates and myriapods,
      whereas the other included crustaceans plus insects, onychophorans plus
      pentastomids, and tardigrades. The pycnogonids were grouped closely with the
      chelicerates. The Cambrian fossil record supports that myriapod-chelicerate and
      crustacean-insect (including tardigrades, onychophorans, and pentastomids) stems
      arose separately from a protoarthropod (perhaps nonarthropodized animal, such as
      a lobopod which has noncalcified cuticles, and nonjointed legs). Thus, the
      acquisition of truly arthropod characters occurred independently in the two
      stems. In this case, nonarthropodized characters of tardigrades, onychophorans,
      and pentastomids are assumed to be primitive.

PMID- 9571636
TI  - Expression of the CIP1 gene induced under cadmium stress in Candida sp.
AB  - Cadmium is a toxic heavy metal with no known biological activity. Differential
      display of mRNA was employed to isolate cDNA corresponding to the transcript that
      is induced in cadmium-treated Candida sp. In this report we describe the
      molecular characterization of the CIP1 gene, which was shown to be rapidly
      induced after cadmium treatment. Northern blot analysis showed that the CIP1
      transcript was not present in normal cells, but accumulated at higher levels in
      cadmium-treated cells. Treatment of other heavy metals such as copper, mercury,
      lead, zinc, or heat-shock had no effect on the expression of the CIP1 gene.
      Sequence analysis of CIP1 revealed that it encodes a 32 kDa hydrophobic protein
      that contains a putative transmembrane domain. The deduced amino acid sequence of
      CIP1 showed a little homology with isoflavone reductase of plants. From the
      promoter sequence analysis, we also identified a sequence similar to pas, a
      cadmium-responsive element of the ParA gene in tobacco. Our results suggest that
      Candida CIP1 may play a crucial role in the establishment of specific cellular
      response to stress evolved by the cadmium treatment.

PMID- 9571637
TI  - Rac GTPase activity is essential for EGF-induced mitogenesis.
AB  - Rac, a member of the Rho family GTPases, has been implicated in the regulation of
      a wide range of biological processes including actin remodeling, cell
      transformation, G1 cell cycle progression, and gene expression. To determine
      whether Rac GTPase activity is required for epidermal growth factor-induced
      mitogenesis, Rat-2 stable cells expressing a dominant-negative Rac1 mutant,
      RacN17, were prepared. Exposure to EGF exhibited a significantly restricted
      growth response in Rat-2-RacN17 cells compared to Rat-2 parental cells,
      suggesting an essential role of Rac in EGF-induced mitogenesis. In contrast,
      addition of lysophosphatidic acid exerted the same level of growth in Rat-2 and
      Rat-2-RacN17 cells. To gain further evidence for the essential role of Rac in EGF
      induced mitogenesis, we performed the microinjection experiment. EGF-induced DNA
      synthesis was significantly blocked by microinjection of recombinant RacN17
      protein, and not control IgG. Our further study to analyze the downstream
      mediator of Rac in EGF-signaling to mitogenesis demonstrated that Rac-activated
      phospholipase A2 plays a critical role. Taken together, our results suggest that
      the "Rac and Rac-activated PLA2" cascade is one of the major mitogenic pathways
      induced by EGF.

PMID- 9571638
TI  - Expression of C5 protein, the protein component of Escherichia coli RNase P, from
      the tac promoter.
AB  - The accurate function of C5 protein, the protein component of Escherichia coli
      RNase P, is uncertain in vivo. A controllable expression system for C5 protein
      was constructed which can be used to investigate effects of C5 protein on various
      cellular functions including biosynthesis of RNase P in vivo. The semisynthetic
      rnpA gene encoding C5 protein was fused to the tac promoter of the pKK223-3
      expression vector. This tac promoter expression system produced a high level of
      C5 protein upon induction with isopropyl-beta-D-thiogalacto-pyranoside. When the
      overexpressed C5 protein was purified and used for reconstitution of RNase P, the
      reconstituted enzyme was active. The N-terminal amino acid of the overexpressed
      C5 protein was leucine specified by the second codon of the rnpA gene. The more
      controllable expression system was constructed by introducing the lacIq gene into
      the vector sequence itself.

PMID- 9571639
TI  - Triprimer-PCR method: rapid and reliable detection of transgenes in transgenic
      rice plants.
AB  - We designed a triprimer-PCR system for detection of transgenes and applied for
      analysis of two different kinds of transgenic rice plants, which were previously
      transformed with the plasmids pBY605RR or pARP7 containing a maize ribosome
      inactivating protein gene, Zmcrip3a, and a herbicide-resistant gene, bar. Genomic
      Southern-blot analysis demonstrated that the transgenes were stably inherited to
      their R1 progenies without changes in configuration. The resulting data were used
      as a reference for triprimer-PCR analysis. The triprimer-PCR system uses an
      endogenous gene as an internal standard which shares an identical priming site
      for one primer with a transgene while each of the other two primers is specific
      to either the transgene or the endogenous gene. Triprimer-PCR analysis was
      carried out on genomic DNA isolated from 24 different progenies of the pBY605RR-
      and the pARP7-transformed lines that contain different copy numbers of
      transgenes. The RbcS:Zmcrip3a junction region of the pBY605RR integrated in rice
      chromosomes, together with the endogenous RbcS, was efficiently amplified,
      producing 440 and 250 bp expected PCR products. Also, the Act1:Zmcrip3a junction
      region of the transgene pARP7 with the endogenous Act1 was similarly amplified,
      producing 540 and 340 bp expected PCR products. The two PCR products in each set
      of experiments were observed consistently and independently of copy numbers or
      rearrangements of the transgene. Thus, the triprimer-PCR strategy may provide a
      rapid and reliable method for confirming transformation or analyzing segregation
      of transgenes at the molecular level.

PMID- 9571640
TI  - Structure of a polyubiquitin gene in Nicotiana tabacum.
AB  - Using a tobacco ubiquitin cDNA clone as a probe, a genomic clone in EMBL3 coding
      for a tobacco polyubiquitin protein was isolated. Southern blot hybridization of
      the genomic clone with the cDNA clone identified a BamHI/EcoRI fragment of 2.5 kb
      to contain the coding region of polyubiquitin, and thus the fragment was
      subcloned into a plasmid vector. Nucleotide sequence determination of the clone
      identified an open reading frame for the four head-to-tail repeats of ubiquitin
      monomer of 76 amino acids interrupted by an intron sequence of 55 nucleotides.
      The four ubiquitin units were completely conserved except for the extra glutamine
      at the carboxy terminus of the last ubiquitin monomer. At the 5'-region upstream
      of the open reading frame, a sequence of 630 nucleotides was determined. In this
      region, well-known regulatory sequences such as the CCAAT box, TATA box and heat
      shock elements could not be located; instead, a region very rich in C and T and
      repeats of CA was noticed. In the 3'-downstream region of the open reading frame,
      a sequence of 474 nucleotides was determined which contained putative
      polyadenylation signals and a GU-rich region.

PMID- 9571641
TI  - Molecular characterization of a cDNA encoding chloroplastic fructose-1,6
      bisphosphatase from soybean (Glycine max L.).
AB  - A full-length cDNA of soybean chloroplastic fructose-1,6-bisphosphatase was
      cloned and sequenced. The cDNA contained 1321 bp with 5' (26 bp) and 3' (88 bp)
      untranslated regions. The open reading frame of the cDNA contained 1206 bp
      corresponding to a polypeptide of 402 amino acids with 50 amino acid residues of
      a transit peptide at N-terminus that is necessary for transport into the
      chloroplast. A unique site relevant to the action of thioredoxin f was conserved
      at 221 amino acid residue. Northern blot analysis indicated that the expression
      of the enzyme was regulated by light illumination.

PMID- 9571642
TI  - Analysis of the envelope region of hepatitis G virus isolated from Korean
      patients.
AB  - The genetic diversity of hepatitis G virus (HGV) was investigated. By using a RT
      PCR procedure, 14% of either HBV (hepatitis B virus)- or HCV (hepatitis C virus)
      positive Korean hepatitis patients were proved to be HGV positives. Nucleotide
      sequences in the E1 region of the eight isolates from Korean patients and the six
      previously reported isolates were compared. Nucleotide substitutions spread
      uniformly throughout the E1 region. Sequence homology among the Korean isolates
      was 84-99% and 88-99% at the nucleotide and amino acid sequences, respectively,
      whereas those from different geographic areas was slightly lower at both levels.
      At least two genotypes might exist among the Korean HGV isolates. Compared to the
      corresponding region of HCV, the E1 sequence from HGV is moderately conserved. In
      addition, as frameshift mutations were observed in most of the Korean isolates
      compared to the prototype HGV sequence, the Korean isolates might not use the
      translational initiation site of the prototype HGV for polyprotein translation.
      Because a putative signal sequence of E1 for entry into endoplasmic reticulum
      starts from the N-terminus of the polyprotein, and capsid-like peptides composed
      of basic amino acids could not be detected from the upstream region of E1, the
      core protein of HGV is absent, or at least not present, at the region next to 5'
      UTR. Therefore, HGV could be clearly distinguished from other genera of
      Flaviviridae.

PMID- 9571643
TI  - The tachykinin NK1 receptor. Part II: Distribution and pathophysiological roles.
AB  - The tachykinin NK1 receptor is widely distributed in both the central and
      peripheral nervous system. In the CNS, NK1 receptors have been implicated in
      various behavioural responses and in regulating neuronal survival and
      degeneration. Moreover, central NK1 receptors regulate cardiovascular and
      respiratory function and are involved in activating the emetic reflex. At the
      spinal cord level, NK1 receptors are activated during the synaptic transmission,
      especially in response to noxious stimuli applied at the receptive field of
      primary afferent neurons. Both neurophysiological and behavioural evidences
      support a role of spinal NK1 receptors in pain transmission. Spinal NK1 receptors
      also modulate autonomic reflexes, including the micturition reflex. In the
      peripheral nervous system, tachykinin NK1 receptors are widely expressed in the
      respiratory, genitourinary and gastrointestinal tracts and are also expressed by
      several types of inflammatory and immune cells. In the cardiovascular system, NK1
      receptors mediate endothelium-dependent vasodilation and plasma protein
      extravasation. At respiratory level, NK1 receptors mediate neurogenic
      inflammation which is especially evident upon exposure of the airways to
      irritants. In the carotid body, NK1 receptors mediate the ventilatory response to
      hypoxia. In the gastrointestinal system, NK1 receptors mediate smooth muscle
      contraction, regulate water and ion secretion and mediate neuro-neuronal
      communication. In the genitourinary tract, NK1 receptors are widely distributed
      in the renal pelvis, ureter, urinary bladder and urethra and mediate smooth
      muscle contraction and inflammation in response to noxious stimuli. Based on the
      knowledge of distribution and pathophysiological roles of NK1 receptors, it has
      been anticipated that NK1 receptor antagonists may have several therapeutic
      applications at central and peripheral level. At central level, it is speculated
      that NK1 receptor antagonists could be used to produce analgesia, as antiemetics
      and for treatment of certain forms of urinary incontinence due to detrusor
      hyperreflexia. In the peripheral nervous system, tachykinin NK1 receptor
      antagonists could be used in several inflammatory diseases including arthritis,
      inflammatory bowel diseases and cystitis. Several potent tachykinin NK1 receptor
      antagonists are now under evaluation in the clinical setting, and more
      information on their usefulness in treatment of human diseases will be available
      in the next few years.

PMID- 9571644
TI  - Action of AT1 subtype angiotensin II receptors of the medial preoptic area on
      gonadotropins and prolactin release.
AB  - This study determined the effect of the selective angiotensin II (A II) AT1
      receptor subtype antagonist losartan in the medial preoptic area (MPOA) of
      ovariectomized rats, treated with estrogen or untreated, on the release of
      gonadotropins (LH and FSH) and prolactin (PRL). The MPOA is sensitive to the
      action of A II and contains cell bodies of neurons producing luteinizing hormone
      releasing hormone and a large density of estradiol receptors. Plasma FSH was not
      altered in any situation. However, losartan blocked and estradiol facilitated the
      stimulating and inhibitory effects of A II microinjection into the MPOA on LH and
      PRL secretion, respectively. The results indicate that these effects are mediated
      by AT1 receptors in the MPOA and that estradiol may modulate them. On the other
      hand, losartan itself reduced LH secretion in ovariectomized rats, indicating
      that the increase in the secretion of this hormone, after removal of the negative
      feedback caused by estradiol, is due, at least in part, to the action of A II on
      AT1 receptors of the MPOA.

PMID- 9571645
TI  - The role of cytokines in MET-enkephalin-modulated nitric oxide release.
AB  - In the present study the in vitro and in vivo effect of Met-enkephalin (MENK) on
      nitric oxide (NO) release by mouse peritoneal macrophages was evaluated. While in
      vitro MENK was ineffective unless combined with suboptimal concentrations of
      recombinant murine interferon gamma, in vivo all the doses (2.5, 5 or 10 mg/kg
      bw) bimodaly modulated NO release. Only the stimulative (2.5 and 10 mg/kg bw) and
      not the suppressive (5 mg/kg bw) dose of MENK was opioid receptor-mediated as
      demonstrated by abolishing the effect by naloxone. The stimulative effect of the
      low (2.5 mg/kg bw) dose, that was observed only if MENK was injected p.m., was
      associated with the IL production and IFN gamma as demonstrated by abolishing the
      effect by specific antibodies. The data additionally support the idea that opioid
      mediated responses might be to a large degree mediated by the release of
      cytokines.

PMID- 9571646
TI  - Neuropeptide Y in the magnocellular hypothalamic neurons of obese Zucker rats.
AB  - The obesity syndrome in Zucker rats is associated with an elevated neuropeptide Y
      (NPY) content in the hypothalamus. It is recognized that the axons of NPY-ergic
      neurons arriving from the arcuate nucleus and the midbrain are the major source
      of NPY in this area. In magnocellular hypothalamic neurosecretory neurons (MCN)
      of normal rats NPY is expressed only in response to hyperosmotic stimulation.
      This study used immunohistochemistry with colchicine treatment aimed at MCN to
      compare NPY localization in obese (fa/fa) and in lean (Fa/Fa) Zucker rats. It was
      found that the obese (fa/fa), in contrast to the lean (Fa/Fa) Zucker rat,
      displays NPY immunoreactivity in numerous MCN of the paraventricular, supraoptic
      as well as accessory neurosecretory nuclei. This finding suggests local synthesis
      of NPY in the MCN of obese (fa/fa) rats and involvement of hydro-osmotic
      disorders in the Zucker syndrome of obesity.

PMID- 9571647
TI  - Changes in oxytocin content in rat brain during morphine withdrawal.
AB  - In this study the modification in the oxytocin content in different hypothalamic
      nuclei during morphine withdrawal was analysed. Male rats were implanted with
      placebo (naive) or morphine (tolerant/dependent) pellets for 7 days. On day 7,
      groups of rats received an acute injection of saline s.c. (control) or naloxone
      (1 mg/kg s.c.) and were decapitated 30 min later. After administration of
      naloxone to tolerant rats (withdrawal) an increase in the oxytocin content in the
      paraventricular nucleus (PVN) and median eminence (ME) was found. No changes were
      found in the arcuate nucleus (AN) and supraoptic nucleus (SON). Present data
      demonstrate that administration of naloxone to tolerant rats alters the brain
      oxytocin system, which suggests that this peptide might contribute to the
      behavioural, emotional and neuroendocrine response to opioid.

PMID- 9571648
TI  - On the role of cholecystokinin in the mediation of spinal reflex excitability in
      intact and axotomized rats.
AB  - The effects of intrathecal (i.t.) administration of cholecystokinin (CCK) on the
      hindlimb flexor withdrawal reflex were compared in decerebrate, spinalized,
      unanaesthetized rats with intact sciatic nerves or 14-26 days after unilateral
      transection of the sciatic nerve. The effect of CI-988, a CCK-B receptor
      antagonist, on the facilitation of the flexor reflex induced by conditioning
      stimulation (CS) of C-afferents was also examined. Intrathecal CCK induced
      facilitation of the flexor reflex over the dose range of 10 ng-1 micrograms in
      rats with intact and sectioned sciatic nerves. However, the facilitation induced
      by CCK in axotomized rats was significantly reduced compared with nerve intact
      animals. CI-988 did not block the facilitation of the flexor reflex induced by
      the CS and the increases in reflex magnitude during the CS train (wind-up) in
      rats with intact and sectioned sciatic nerves. The present results indicate that
      the excitatory effect of CCK on the spinal cord is reduced after axotomy,
      suggesting that nerve section may induce transsynaptic changes in the spinal cord
      leading to hyposensitivity to CCK. Furthermore, it is suggested that CCK may not
      play a significant role in the phenomenon of wind-up and central sensitization
      after repetitive C-fiber input under normal conditions or after axotomy, when
      expression of CCK and CCK-B receptors are increased in sensory neurons.

PMID- 9571649
TI  - A role for the octamer-binding protein in preprotachykinin-A gene expression.
AB  - A rat Preprotachykinin-A promoter fragment has been previously identified which
      supports reporter gene activity in primary cultures of adult dorsal root ganglion
      neurons. That study demonstrated that two promoter domains which exhibit enhancer
      activity in these neurons are bound by the same classes of transcription factors.
      Further, the two domains exhibit similarities with respect to the relationship of
      bound transcription factors within each domain. This suggests that these domains
      may function in an identical manner or may act synergistically to regulate gene
      expression. These domains contain recognition motifs for at least three classes
      of transcription factors: octamer-binding proteins, Sp1-related proteins and an
      as yet unidentified but distinct factor. The definition of an octamer-binding
      protein site within these domains is of interest, as this class of factor has
      recently been suggested as mediating the effect of nerve growth factor in sensory
      neurons. Nerve growth factor is a well-characterized regulator of
      preprotachykinin-A gene expression. Definition of these sites within the promoter
      allows for the design of rational experiments to address the mechanism of
      transcriptional regulation of the rat preprotachykinin-A gene.

PMID- 9571650
TI  - Ifenprodil blocks the excitatory effects of the opioid peptide dynorphin 1-17 on
      NMDA receptor-mediated currents in the CA3 region of the guinea pig hippocampus.
AB  - This study found that dynorphin had a biphasic concentration response
      relationship on N-methyl-D-aspartate (NMDA) receptor-mediated currents in the CA3
      region of the guinea pig hippocampal slice. A previous study demonstrated that
      the inhibitory effect was mediated by a kappa 2 opioid receptor. In the present
      study, the polyamine site antagonist ifenprodil converted dynorphin's biphasic
      concentration response relationship to a monophasic inhibitory curve. The
      polyamine diethylenetriamine also blocked dynorphin's excitatory actions. The
      combination of dynorphin 1-17 and naloxone produced neurotoxicity, presumably as
      a result of dynorphin's excitatory actions on NMDA receptors. In addition, the
      release of endogenous dynorphin from mossy fibers in the presence of naloxone
      injured the cells. Ifenprodil prevented the neurotoxicity of both applied and
      released dynorphin. These findings suggest that dynorphin acts at a polyamine
      site to produce its excitatory effects and, further, suggest that dynorphin may
      mediate some neuropathologies through its interaction at this site.

PMID- 9571651
TI  - Serotonin in aging, late-life depression, and Alzheimer's disease: the emerging
      role of functional imaging.
AB  - Serotonin (5-HT) neuron and neurotransmitter loss in normal aging and
      neuropsychiatric diseases of late life may contribute to behavioral changes
      commonly observed in the elderly population. Extensive evidence implicates a
      deficit in serotonergic neurotransmission in the development of major depression.
      It has been further suggested that the age-related changes in 5-HT neurons may
      predispose the elderly to develop depression. There is also increasing evidence
      that a combination of disturbances in cholinergic and serotonergic function may
      play a role in cognitive impairment in Alzheimer's disease (AD), with
      serotonergic dysfunction potentially responsible for a significant portion of the
      behavioral aspects of the disease. This implication of the 5-HT system in aging
      and age-related cognitive and mood disorders rests in large part on post mortem
      studies and animal models, which are limited in their capacity to predict dynamic
      human biochemical-behavior relationships or to accurately model the living human
      brain. Initial applications of functional brain imaging with positron emission
      tomography (PET) in the in vivo study of the brain in aging depression, and
      dementia focused on characterizing alterations in physiological measurements of
      cerebral metabolism and perfusion. However, recent advances in PET
      radiochemistry, instrumentation, and image processing have paved the way for
      noninvasive means to test specific hypotheses regarding the direct involvement of
      5-HT neurons in the behavioral features of aging and to define and monitor
      therapeutic regimens for neuropsychiatric conditions of late life. Coupling of
      clinical trials in well-characterized subject populations with PET imaging using
      ligands specific for 5-HT receptor subtypes and transporter proteins promises to
      increase our understanding of the role of the 5-HT system in affective and
      cognitive aspects of treatment response. Longitudinal studies in aging, late-life
      depression, and AD are also needed to evaluate the complex interplay between
      neurodegenerative processes and serotonergic neurotransmission.

PMID- 9571652
TI  - The serotonin reuptake inhibitor sertraline reduces excessive alcohol consumption
      in nonhuman primates: effect of stress.
AB  - Many monkeys that are reared without adult influence, with only peers,
      voluntarily consume alcohol in amounts producing intoxication on a relatively
      regular basis. Using a cross-over design, eight adolescent, peer-reared rhesus
      monkeys were allowed unfettered access to an 8.4% ethanol solution and treated
      with 20 mg/kg/24 h of sertraline during three phases: home-cage, social
      separation, and reunion with cage-mates. Although there was no immediate effect,
      sertraline reduced alcohol consumption beginning the second week of home-cage
      treatment, but only in subjects that consumed large amounts of alcohol.
      Initially, the social separation stress caused the sertaline-treated subjects'
      alcohol consumption rates to return to baseline levels, but when the stress was
      repeated, alcohol consumption fell below baseline and placebo levels. Sertraline
      treatment was ineffective in reducing consumption during the stressful period of
      home-cage reunion, a period characterized by high levels of aggressive behavior.
      Behaviorally, sertraline reduced aggression and anxiety-like self-directed
      behaviors. Our findings provide evidence that sertraline may be an effective
      pharmacological treatment for excessive alcohol consumption and aggression. On
      the other hand, stress during treatment may reduce sertraline's effectiveness as
      a treatment for excessive alcohol consumption.

PMID- 9571653
TI  - Treatment of refractory depression with high-dose thyroxine.
AB  - In an open clinical trial we investigated whether addition of supraphysiological
      doses of thyroxine (T4) to conventional antidepressant drugs has an
      antidepressant effect in therapy-resistant depressed patients. Seventeen severely
      ill, therapy-resistant, euthyroid patients with major depression (12 bipolar,
      five unipolar) were studied. The patients had been depressed for a mean of 11.5
      +/- 13.8 months, despite treatment with antidepressants and, in most cases,
      augmentation with lithium, carbamazepine, and neuroleptics. Thyroxine was added
      to their antidepressant medication, and the doses were increased to a mean of 482
      +/- 72 micrograms/day. The patients' scores on the Hamilton rating Scale for
      Depression (HRSD) declined from 26.6 +/- 4.7 prior to the addition of T4 to 11.6
      +/- 6.8 at the end of week 8. Eight patients fulfilled the criteria for full
      remission (a 50% reduction in HRSD score and a final score of < or = 9) within 8
      weeks and two others fully remitted within 12 weeks. Seven patients did not
      remit. The 10 remitted patients were maintained on high-dose T4 and followed up
      for a mean of 27.2 +/- 22.0 months. Seven of these 10 remitted patients had an
      excellent outcome, two had milder and shorter episodes during T4 augmentation
      treatment, and one failed to profit from T4 treatment during the follow-up
      period. Side effects were surprisingly mild, and no complications were observed
      at all. In conclusion, augmentation of conventional antidepressants with high
      dose T4 proved to have excellent antidepressant effects in approximately 50% of
      severely therapy-resistant depressed patients.

PMID- 9571654
TI  - Tobacco smoking and nicotine neuropsychopharmacology: some future research
      directions.
AB  - Although nicotine is acknowledged as the major pharmacologically active chemical
      in tobacco that accounts for its continued use, there is a need for much further
      research. It is necessary to systematically compare the complex pharmacological
      actions of pure nicotine with those of tobacco, using different routes of
      administration and, therefore, rates of absorption. Tobacco smoking produces
      several important behavioral and central nervous system effects. More research is
      needed to determine the role of nicotine versus the many other substances present
      in tobacco smoke. Although nicotine is the primary pharmacological agent in
      tobacco that maintains its use, other chemicals and their biological mechanisms
      involved in tobacco smoking need to be studied further.

PMID- 9571655
TI  - MDMA elicits behavioral and neurochemical sensitization in rats.
AB  - Rats were treated with repeated injections of saline or one of two doses of (+/
      )3,4-methylenedioxymethamphetamine (MDMA; 5 or 20 mg/kg, s.c.). Rats pretreated
      with either of the two repeated MDMA treatment regimens demonstrated an augmented
      increase in motor activity to an injection of MDMA made 12 days after the last
      repeated injection compared with either the first MDMA injection or MDMA given to
      animals pretreated with repeated saline. Furthermore, animals pretreated with the
      highest dose of repeated MDMA revealed a greater behavioral response to cocaine
      (15 mg/kg, i.p.). Microdialysis was conducted in the nucleus accumbens and the
      capacity of MDMA (5 mg/kg, s.c.) to elevate extracellular dopamine content was
      augmented in rats pretreated with repeated MDMA compared with the animals
      pretreated with repeated saline. These data reveal repeated MDMA administration
      produces behavioral sensitization and enhanced dopamine transmission in the
      nucleus accumbens of rats.

PMID- 9571656
TI  - Genetics, haloperidol, and the Fos response in the basal ganglia: a comparison of
      the C57BL/6J and DBA/2J inbred mouse strains.
AB  - The haloperidol-induced increase of Fos-like immunoreactive (Fos-li) neurons in
      the basal ganglia was compared in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse
      strains. The D2 strain is 10-fold more sensitive than the B6 strain to
      haloperidol-induced catalepsy, a putative animal model of the extrapyramidal
      symptoms (EPS) seen after the administration of typical neuroleptics. In
      contrast, the strains are equally sensitive to the haloperidol facilitation of
      prepulse inhibition of the acoustic startle response, a measure of drug efficacy
      on the mesolimbic dopamine system. The haloperidol effects on Fos-li neurons were
      examined over the range of 0.1 to 6.0 mg/kg; the ED50s for haloperidol-induced
      catalepsy are 0.4 and 3.8 mg/kg in the D2 and B6 strains, respectively. In
      neither the core or shell of the nucleus accumbens nor the caudate-putamen
      (including the dorsolateral aspect) did the D2 strain show a greater Fos response
      compared to the B6 strain. In fact, in the dorsolateral caudate-putamen, the B6
      strain showed a modest but significantly greater Fos response. However, at the
      output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the
      substantia nigra zona reticulata (SNr), the D2 strain consistently showed a
      greater Fos response. These data suggest that the EP and SNr may be important to
      understanding the difference in haloperidol-induced catalepsy between the D2 and
      B6 strains.

PMID- 9571657
TI  - Effects of corticotropin-releasing factor on brain serotonergic activity.
AB  - The serotonergic dorsal raphe nucleus is innervated by corticotropin-releasing
      factor (CRF) and expresses CRF receptors, suggesting that endogenous CRF impacts
      on this system. The present study characterized interactions between CRF and the
      dorsal raphe serotonin (5-HT) system. The effects of intracerebroventricularly
      (i.c.v.) administered CRF on microdialysate concentrations of 5-HT in the lateral
      striatum of freely moving rats were determined. CRF had biphasic effects, with
      0.1 and 0.3 microgram decreasing, and 3.0 micrograms increasing 5-HT dialysate
      concentrations. i.c.v. administration of CRF inhibited neuronal activity of the
      majority of dorsal raphe neurons at both low (0.3 microgram) and high (3
      micrograms) doses. Likewise, intraraphe administration of CRF (0.3 and 1.0 ng)
      had predominantly inhibitory effects on discharge rate. Together, these results
      suggest that CRF is positioned to regulate the function of the dorsal raphe
      serotonergic system via actions within the cell body region. This regulation may
      play a role in stress-related psychiatric disorders in which 5-HT has been
      implicated.

PMID- 9571659
TI  - Reproducibility of retinal thickness measurements in normal eyes using optical
      coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To determine the reproducibility of retinal thickness
      measurements in normal eyes using optical coherence tomography (OCT). PATIENTS
      AND METHODS: Multiple 3.20-mm vertical cross-sectional images through the center
      of fixation of consecutive patients with normal results on ocular examinations
      were obtained. Each image was divided into seven 320-micron segments. Regional
      retinal thicknesses for each section were measured using both the manually
      assisted (requiring observer localization of reflectivity peaks) and the
      automated modes (observer-independent measurement) of the computer software.
      RESULTS: Eighteen right eyes were studied. The mean coefficient of variation was
      less than 10% for all locations using the manually assisted method (average
      standard deviation less than 17 microns [range 9 to 16 microns]). The automated
      method was less reliable, with a coefficient of variation greater than 10% for
      locations within 500 microns of fixation. Automated measurements at fixation were
      the least reproducible because of poor internal limiting membrane reflectivity.
      CONCLUSION: OCT is capable of reproducible measurement of retinal thickness in
      normal eyes. Computer-driven, automated measurement of retinal thickness within
      500 microns of fixation needs to be refined and its reproducibility reassessed in
      this region.

PMID- 9571658
TI  - Early intraocular pressure after phacoemulsification combined with
      trabeculectomy.
AB  - BACKGROUND AND OBJECTIVE: To determine the efficacy of combined
      phacoemulsification--trabeculectomy in preventing early postoperative increases
      in intraocular pressure (IOP). PATIENTS AND METHODS: Eighty patients were
      enrolled in a prospective cohort study. Thirty-six patients with cataracts and
      uncontrolled glaucoma underwent combined phacoemulsification--trabeculectomy, and
      44 patients with cataracts underwent phacoemulsification alone. The operations
      were performed in a standardized manner by one surgeon. IOP was measured at 4
      hours, 1 day, and 7 days after surgery. The need for intervention (digital
      massage, medications) and the presence of complications were documented. RESULTS:
      Four hours after surgery, 5.5% of patients undergoing the combined procedure had
      IOPs greater than 30 mm Hg, compared with 22.7% of phacoemulsification patients
      (P < .05). No significant difference in IOP was found between the groups at
      postoperative day 1 or day 7. CONCLUSION: These results suggest that combined
      phacoemulsification-trabeculectomy protects against early postoperative
      elevations in IOP. This finding may influence the surgical management of
      cataracts in patients with poorly controlled glaucoma and significant compromise
      of visual field or optic nerve.

PMID- 9571660
TI  - The course of age-related macular degeneration following bilateral cataract
      surgery.
AB  - BACKGROUND AND OBJECTIVE: Progression of age-related macular degeneration (AMD)
      following cataract surgery has been described. The aim of this study was to
      investigate whether an uneventful postoperative maculopathic course in one eye
      (the first eye) may predict a similar prognosis for the fellow eye (the second
      eye). PATIENTS AND METHODS: Thirty-three patients with bilateral, similar, early
      AMD (defined by the presence of drusen and/or pigmentary abnormalities on fundal
      examinations and by the absence of late leakage as documented by fluorescein
      angiography) who had undergone unilateral cataract surgery, had had a stable
      postoperative maculopathic course following the first operation, and were
      scheduled for cataract surgery in the second eye were prospectively observed for
      at least 1 year after the second operation. The course of maculopathy of the
      second eye was compared with that of the first eye during the follow-up period of
      the second eye. RESULTS: A total of 9 of the second eyes (27.2%) showed
      progression to wet AMD. Of these, 1 patient (3%) had progression in both eyes and
      8 patients (24.2%) had progression in the second eye only. The conditions of 2 of
      the first operated on eyes (6.1%) deteriorated (P < .05). Hypertension (P < .05),
      soft drusen (P < .01), and Nd:YAG laser capsulotomy (P < .05) were risk factors
      for development of wet AMD. CONCLUSION: In this study, 24.2% of the patients with
      early AMD who underwent bilateral cataract surgery and had an uneventful
      maculopathic course in the first eye had wet AMD in the second eye. Thus,
      patients with early AMD and soft drusen undergoing bilateral cataract surgery
      should be monitored for early detection of progression of maculopathy. Further
      prospective studies are needed to determine the course of maculopathy following
      cataract surgery.

PMID- 9571661
TI  - Time-kill profiles of Enterococcus to antibiotics used for intravitreal therapy.
AB  - BACKGROUND AND OBJECTIVE: To determine and then compare the time-kill profiles of
      Enterococcus to antibiotics used for intravitreal therapy. PATIENTS AND METHODS:
      The time-kill profiles of four endophthalmitis isolates of Enterococcus faecalis,
      one vancomycin-resistant E. faecalis isolate, and three vancomycin-resistant
      isolates of E. faecium were determined against vancomycin, amikacin, cefazolin,
      gentamicin, ampicillin, ciprofloxacin, ceftazidime, clindamycin, and the
      combinations of vancomycin and amikacin, vancomycin and ceftazidime, vancomycin
      and gentamicin, vancomycin and ampicillin, cefazolin and gentamicin, and
      ampicillin and gentamicin. RESULTS: No single antibiotic or combination was
      bactericidal (defined as 99.9% kill) to all isolates of Enterococcus. Gentamicin
      was bactericidal to all E. faecalis isolates. None of the tested antibiotics were
      bactericidal to vancomycin-resistant E. faecium. CONCLUSIONS: The time-kill
      profiles demonstrated that vancomycin and ceftazidime did not produce a 99.9%
      kill for E. faecalis in this small study. Gentamicin combined with either
      cefazolin or ampicillin had somewhat better bactericidal activity and should be
      considered as an alternative therapy. Novel therapy may be necessary to treat
      endophthalmitis because of vancomycin-resistant Enterococcus, depending on the
      susceptibility patterns of the individual isolate and the response to initial
      therapy.

PMID- 9571662
TI  - Evaluation of endothelial function in postkeratoplasty eyes.
AB  - BACKGROUND AND OBJECTIVE: To evaluate corneal endothelium function in
      postkeratoplasty eyes. PATIENTS AND METHODS: Endothelial function was assessed in
      23 clear corneal grafts. After a measurable corneal edema was induced by soft
      contact lens wear, serial pachometric readings were taken for 3 hours to arrive
      at the percentage recovery per hour (PRPH) index. RESULTS: The assessed PRPH
      values of the clear corneal grafts ranged from 24.6% to 73.0%, with a mean value
      of 51.8% +/- 12.2%. Of the six corneal grafts that demonstrated an initial PRPH
      value of less than 47.5%, four became edematous within 6 months of follow-up.
      CONCLUSIONS: Assessed PRPH, as an in vivo-measured index of endothelial function,
      is a valuable method for monitoring endothelial function in postkeratoplasty
      eyes. The low PRPH index identifies eyes at risk of spontaneous nonimmunologic
      failures.

PMID- 9571663
TI  - A comparison of corneal autografts with homografts.
AB  - BACKGROUND AND OBJECTIVE: To determine whether ensured graft acceptance through
      the use of corneal autografts yields a better outcome than when standard
      homografts are used. PATIENTS AND METHODS: Four patients who needed a corneal
      transplant in one eye and who had a blind fellow eye underwent a corneal
      autograft in the eye with corneal pathology. RESULTS: Three of the four patients
      had clear grafts on long-term follow-up, and no patient experienced immunologic
      graft rejection. However, two of the four patients had large amounts of
      astigmatism postoperatively. CONCLUSION: Autografts provided protection against
      immunologic graft rejection. However, because corneal autografts yielded
      unpredictable amounts of astigmatism, their outcomes are not necessarily better
      than those of homografts.

PMID- 9571664
TI  - The effects of RGD (Arg-Gly-Asp) peptides on glaucoma filtration surgery in
      rabbits.
AB  - BACKGROUND AND OBJECTIVE: Integrins are the main mediators of the interaction
      between fibroblasts and extracellular matrix (ECM) during scar formation. The
      adhesion motive RGD (Arg-Gly-Asp) is contained in the ECM and is recognized by
      the integrin receptor. Soluble peptides containing the RGD sequence can compete
      with -RGD- contained in the ECM for binding to the integrin receptor and thus
      prevent cell adhesion and scar formation. MATERIALS AND METHODS: The peptides RGD
      (p602), GRGDSP (p603), GRGDSPCA (p604), and GGRGDSPCA (p605) were used in 25
      glaucoma filtering surgeries in rabbits (five eyes per peptide and five with
      saline). RESULTS: Postoperative subconjunctival injections of peptides were given
      at days 0, 4, 8, 12, and 16. Bleb size, bleb survival, and signs of toxicity were
      examined. The GRGDSPCA and GGRGDSPCA showed an increase in bleb formation, size,
      and survival with no clinical signs of toxicity compared with controls (P <
      .008). Histopathologic evaluation confirmed inhibitory effects in scar formation
      with bleb formation, and transmission electron microscopy demonstrated that there
      was no toxicity to the ciliary body. CONCLUSION: These peptides were effective in
      controlling scar formation in glaucoma filtering surgery.

PMID- 9571665
TI  - Penetrating keratoplasty with a valved glaucoma drainage implant for congenital
      glaucoma and corneal scarring secondary to hydrops.
AB  - The simultaneous management of glaucoma and corneal opacification is sometimes
      required in infants with severe congenital glaucoma if timely visual
      rehabilitation is to be achieved. A 1-month-old female infant presented with an
      enlarged, protuberant, opaque cornea in each eye and elevated intraocular
      pressure. An intrastromal, fluid-filled cleft was noted in both corneas. It
      resolved over 3 weeks as corneal scarring progressed. Peripheral corneal clearing
      allowed a view of an essentially normal anterior chamber. Penetrating
      keratoplasty and Ahmed (New World Medical Inc., Rancho Cucamonga, CA) valve
      implant surgery with mitomycin-C were performed simultaneously in the two eyes 1
      months apart. At 15 months of age, the patient's grafts were clear and the
      intraocular pressure was well controlled in both eyes. One eye required multiple
      procedures for eventual glaucoma control. No postoperative overfiltration
      occurred. The authors conclude that the use of a valved implant should be
      considered in patients who require urgent simultaneous corneal and glaucoma
      surgery for severe congenital glaucoma. This combination may improve early
      postoperative control of aqueous outflow and positively affect long-term graft
      survival in these difficult cases.

PMID- 9571666
TI  - Recalcitrant malignant glaucoma following pars plana vitrectomy, scleral buckle,
      and extracapsular cataract extraction with posterior chamber intraocular lens
      implantation.
AB  - Pars plana vitrectomy is employed to treat cases of aqueous misdirection that are
      refractory to medical and laser treatment. The authors describe a 65-year-old man
      without previous aqueous misdirection in whom this condition developed after a
      procedure that included pars plana vitrectomy. The aqueous misdirection recurred
      despite multiple interventions, including medical treatment, transiently
      successful Nd:YAG laser capsulo-hyaloidotomy, and surgical disruption of the
      anterior hyaloid face. It finally resolved after repeated pars plana vitrectomy
      with hyaloido-capsulo-iridectomy. There has been no recurrence 7 months after
      this procedure. The authors conclude that the surgical treatment of aqueous
      misdirection refractory to more conservative measures should include adequate
      disruption of the anterior hyaloid to prevent recurrence.

PMID- 9571667
TI  - Corneal melting and scleromalacia perforans in a patient with pyoderma
      gangrenosum and acute myeloid leukemia.
AB  - Postoperative endophthalmitis may present in an atypical fashion (absent or
      minimal anterior chamber reaction) in the presence of underlying
      immunosuppressive disorder. The authors describe an apparently healthy 58-year
      old man who displayed endophthalmitis with minimal anterior chamber reaction
      following penetrating keratoplasty for granular corneal dystrophy with underlying
      acute myeloid leukemia. Scleromalacia perforans in association with pyoderma
      gangrenosum subsequently developed, leading to ciliary staphyloma and corneal
      melting. Pyoderma gangrenosum is an uncommon, idiopathic skin disease that may
      also have ocular manifestations.

PMID- 9571668
TI  - Exudative retinal detachment in X-linked retinoschisis.
AB  - X-linked retinoschisis is a vitreoretinal dystrophy characterized by foveal and
      peripheral retinoschisis in the nerve fiber layer. Although many associated
      peripheral retinal findings have been reported, few reports have described
      massive exudative retinal detachments in patients with X-linked retinoschisis.
      The authors report the unusual occurrence of Coats'-like exudative retinopathy in
      two patients with X-linked retinoschisis. Both patients had peripheral massive
      exudative retinal detachments.

PMID- 9571669
TI  - An intraocular foreign body masquerading as idiopathic chronic iridocyclitis.
AB  - The authors report a case of presumed idiopathic chronic iridocyclitis in which
      an intraocular foreign body (IOFB) was finally identified. There was no history
      of prior eye trauma. Ophthalmologic and laboratory evaluations were inconclusive.
      Seven months following unsuccessful medical treatment of the iritis and given the
      patient's occupational history, a skull x-ray was performed followed by computed
      tomography of the orbits. A metallic IOFB was identified in the pars plicata and
      was surgically removed with resolution of the inflammation. The possibility of an
      IOFB should always be entertained in idiopathic iridocyclitis refractory to
      medical treatment, even when there is no history of ocular trauma.

PMID- 9571671
TI  - Using the phacoemulsification crescent knife in dacryocystorhinostomy.
AB  - Dacryocystorhinostomy is an effective treatment for nasolacrimal duct
      obstruction. Most techniques employ a conventional blade or knife in making the
      incision of the nasal mucosa and lacrimal sac. The authors describe the use of a
      phacoemulsification crescent knife for this purpose. This technique can be
      effective and at the same time safer and easier to perform.

PMID- 9571670
TI  - Isolated posterior capsule rupture in blunt trauma: pathogenesis and management.
AB  - Although blunt ocular trauma frequently-damages the crystalline lens, isolated
      rupture of the posterior capsule is an infrequently reported occurrence. The
      authors describe three patients with this unusual presentation. All patients
      underwent cataract extraction and intraocular lens (IOL) implantation using a
      limbal approach. There were no intraoperative complications. All patients
      achieved good postoperative visual acuity with well-positioned posterior chamber
      IOLs (in-the-bag in two eyes, sulcus fixated in one eye). Isolated rupture of the
      posterior capsule in young patients can be safely managed using the limbal
      approach and implantation of posterior chamber IOLs, is possible.

PMID- 9571672
TI  - Bacterial contamination of the pressure receiver of a vitrectomy machine.
AB  - On a routine sterility check, the authors found bacteria in their vitrectomy
      machine. Serratia marcescens was detected in the pressure receiver of a roller
      pump vitrectomy machine. The authors improved the machine by installing a
      millipore filter in front of the receiver that prevents bacteria from entering it
      without interfering with the pressure measurements. The origin of Serratia was
      probably a patient with endophthalmitis who was operated on long before the
      routine check. Although this appears to be the first report of a bacterial
      contamination of a vitrectomy machine, the results of testing show that this
      situation is indeed possible. The authors strongly recommend routine checks of
      the equipment and suggest mounting an antibacterial filter.

PMID- 9571673
TI  - Caution in physician-owned HMOs.

PMID- 9571674
TI  - Bilateral total knee replacement is relatively safe but carries risks.

PMID- 9571675
TI  - Simultaneous knee replacement is better for the patient.

PMID- 9571676
TI  - Bipolar hemiarthroplasty for primary osteoarthritis of the hip: a review of 41
      cases with 8 to 10 years of follow-up.
AB  - This article reports the results of 41 hips in 36 patients who underwent bipolar
      hemiarthroplasty for primary osteoarthritis of the hip. Surgical technique
      included a complete capsulectomy and light reaming of the acetabulum in all
      patients. The average follow-up was 8.9 years with a minimum of 8 years. Harris
      hip scores improved from 49 preoperatively to 93 at the latest follow-up, with
      95% of the hips rated as excellent or good. Two patients had mild, intermittent
      groin pain, while a third developed recalcitrant pain necessitating revision.
      Migration of the bipolar cup was minimal with an average of 2.3 mm superior and
      2.1 mm medial migration. Survivorship analysis demonstrated an 89.5% survival
      rate at 10 years.

PMID- 9571677
TI  - Distal femoral osteotomy for lateral compartment osteoarthritis of the knee.
AB  - Twenty-one patients with lateral compartment osteoarthritis and valgus deformity
      of the knee underwent distal femoral supracondylar osteotomy (medial closing
      wedge) between 1983 and 1993 with follow-up ranging from 1 to 8 years. Ten knees
      had plaster cast immobilization, 5 had fixation with 2 staples supplemented with
      a plaster cast, and 6 knees had rigid internal fixation with an AO blade plate.
      Thirty-three percent of patients had a satisfactory result using the HSS score,
      and 57% had a satisfactory result using the Knee Society Clinical Rating. Fifty
      seven percent had a significant complication, including severe knee stiffness
      requiring manipulation under anesthesia (48%), nonunion/delayed union (19%),
      infection (10%), and fixation failure (5%). Five (19%) knees required total knee
      replacement within 5 years of surgery. Satisfactory results were obtained only in
      those patients who had less severe degrees of osteoarthritis confined to the
      lateral compartment (grades I to III), adequate correction of valgus deformity
      (the anatomical axis within 2 degrees from zero), and rigid internal fixation to
      permit postoperative early mobilization. These results indicate that distal
      femoral osteotomy is a satisfactory procedure in the young, active patient with
      osteoarthritis of the lateral compartment of the knee, but requires precise
      surgical technique and rigid internal fixation.

PMID- 9571678
TI  - Early rehabilitation after a modified inferior capsular shift procedure for
      multidirectional instability of the shoulder.
AB  - Sixteen patients with multidirectional instability of the shoulder underwent an
      inferior capsular shift procedure with suture anchor augmentation and
      participated in an early motion and strengthening program. Postoperative
      rehabilitation included use of a sling with 0 degree to 90 degrees elevation
      allowed during the first 3 weeks. All patients began isometric shoulder exercise
      by 3 weeks and initiated progressive resistance exercises by 6 weeks postsurgery.
      After an average 20 months of follow-up, 14 patients were evaluated for pain,
      function, range of motion, stability, and activity level. Pain and function
      improved significantly. No patient reported postoperative subluxation or
      dislocation, and 11 of 14 patients had returned to their premorbid activity
      level.

PMID- 9571679
TI  - Osteochondritis dissecans of the elbow managed by Herbert screw fixation.
AB  - Seven patients (eight elbows) with osteochondritis dissecans were treated with
      cancellous bone grafts and internal fixation of the fragment using a Herbert
      screw. Average follow-up was 32 months. All patients were pain-free and returned
      to previous sporting activities. The postoperative range of motion of the elbow
      increased by an average of 18 degrees. Radiographs showed complete reossification
      of the capitular cyst and normally contoured joint surface.

PMID- 9571680
TI  - Posterior atlantoaxial fixation: the Magerl screw technique.
AB  - Atlantoaxial transarticular fixation is a proven stabilization technique used to
      augment conventional sublaminar fusion. Along with its superior biomechanical
      profile comes the inherent risk of neurovascular injury and potential compromised
      fixation during its application. This article presents a detailed systematic
      guide to this procedure including preoperative evaluation, positioning, and the
      more subtle aspects of the surgical technique. A new instrumentation design that
      has enhanced the ease and accuracy of screw placement with less operative
      frustration and potential morbidity of previous systems also is presented.

PMID- 9571681
TI  - Knee proprioception: a review of mechanisms, measurements, and implications of
      muscular fatigue.

PMID- 9571682
TI  - Delayed presentation of popliteal artery injury during Ilizarov limb lengthening.
AB  - Major vascular injury can result during use of the Ilizarov technique for lower
      extremity limb lengthening. Vascular reconstruction may be accomplished while
      leaving the external fixation ring in place. Continued distraction is made
      possible by leaving sufficient redundancy in the vascular graft.

PMID- 9571683
TI  - Osteonecrosis of the proximal tibia.

PMID- 9571684
TI  - Osteotomy for malunion of a radial neck fracture.

PMID- 9571685
TI  - Radiologic case study. Lumbar Scheuermann's disease.

PMID- 9571686
TI  - Exploitation of immune and other defence mechanisms by parasites: an overview.
AB  - Parasites have established numerous strategies for evading host immunity. Such
      tactics promote persistence and chronicity-factors that favour completion of the
      life cycle and transmission to vectors or the environment. This volume explores
      many facets of the interaction between host and parasite that will be critical to
      the development of meaningful vaccines capable of interrupting what has been
      accomplished over centuries of co-evolution.

PMID- 9571687
TI  - Leishmania, macrophages and complement: a tale of subversion and exploitation.
AB  - Leishmania are intracellular protozoan parasites which reside primarily, if not
      exclusively, in host mononuclear phagocytes. Several studies have demonstrated
      that infectious promastigotes rapidly and efficiently fix complement when they
      encounter serum components during their transmission to the mammalian host.
      Activation of the complement system by a microorganism can have 3 distinct
      biological effects. First, fixation of the terminal complement components can
      result in complement-mediated lysis. Second, fixation of the 3rd component of
      complement can lead to opsonization of the organism for uptake by phagocytic
      cells. Finally, the elaboration of the complement anaphylotoxins, C3a and C5a,
      can lead to inflammation. In the present chapter, we discuss the interaction of
      leishmania promastigotes with the complement system. We show that infectious
      promastigotes avoid the lytic effects of complement and resist fixation of the
      terminal complement components. At the same time, however, these organisms depend
      on fixation of opsonic complement to invade host mononuclear phagocytes
      efficiently. We discuss the mechanisms which allow metacyclic leishmania
      promastigotes to exploit the opsonic properties of complement and the receptors
      on macrophages involved in leishmania recognition. The role of complement
      mediated inflammatory processes in the host response to leishmania infection is
      an area which requires additional study.

PMID- 9571688
TI  - The fate and persistence of Leishmania major in mice of different genetic
      backgrounds: an example of exploitation of the immune system by intracellular
      parasites.
AB  - Leishmania spp. are intracellular protozoan parasites that are delivered within
      the dermis of their vertebrate hosts. Within this peripheral tissue and the
      draining lymph node, they find and/or rapidly create dynamic microenvironments
      that determine their ultimate fate, namely their more or less successful
      expansion, and favour their transmission to another vertebrate host though a
      blood-feeding vector. Depending on their genetic characteristics as well as the
      genetic make-up of their hosts, once within the dermis Leishmania spp. very
      rapidly drive and maintain sustained T cell-dependent immune responses that
      arbitrate their ultimate fate within their hosts. The analysis of the parasitism
      exerted by Leishmania major in mice of different genetic backgrounds has allowed
      us to recognize some of the early and late mechanisms driven by this parasite
      that lead to either uncontrolled or restricted parasitism. Uncontrolled
      parasitism by Leishmania major characterizing mice from a few inbred strains
      (e.g. BALB/c) is associated with the expansion of parasite reactive Th2 CD4
      lymphocytes and results from their rapid and sustained activity. In contrast,
      restricted parasitism characteristic of mice from the majority of inbred strains
      results from the development of a polarized parasite-specific Th1 CD4 response.
      This murine model of infection has already been and will continue to be
      particularly instrumental in dissecting the rules controlling the pathway of
      differentiation of T cells in vivo. In the long run, the understanding of these
      rules should contribute to the rational development of novel immunotherapeutic
      interventions against severe infectious diseases.

PMID- 9571689
TI  - The relationship between immunological responsiveness controlled by T-helper 2
      lymphocytes and infections with parasitic helminths.
AB  - It should have been difficult until relatively recently for immunologists to
      ascribe a sound biological reason for the continued possession of the allergic
      phenotype in human populations. Nevertheless, for the past 20 years or so
      textbooks of immunology have routinely exhibited fanciful and perhaps exaggerated
      diagrams as to how IgE and eosinophils killed all helminth parasites. These
      diagrams were largely based on perhaps selective in vitro observations, and it is
      only now that immunoparasitologists, working on human populations under arduous
      conditions in the field, are able to provide data to corroborate these findings,
      and perhaps ascribe a useful purpose for a generally pathological immune response
      termed Type I hypersensitivity. The present paper reviews much of this recent
      literature, and asks a number of pertinent questions relating to the relationship
      between what we now know to be T-helper 2 lymphocyte-driven immunological
      responsiveness and infections with parasitic helminths.

PMID- 9571690
TI  - Modulation of host cell receptors: a mechanism for the survival of malaria
      parasites.
AB  - Intra-erythrocytic stages of malaria parasites can alter the surface of their
      host cells and release toxins which induce the production of cytokines, which in
      turn can up- or down-regulate the expression of adhesion receptors on the surface
      of microvascular endothelial cells. New adhesion receptors on endothelial cells
      provide the parasite with increased chances of survival despite an increasing
      level of host immunity. In order to take advantage of these new opportunities for
      survival, the parasite itself needs to make best use of its considerable ability
      to vary its surface antigens and adherent molecules. The paper describes the
      various players in this survival game and articulates a working hypothesis to
      explain how it may all fit together.

PMID- 9571691
TI  - Immune evasion in malaria: altered peptide ligands of the circumsporozoite
      protein.
AB  - T cells are central to immunity in malaria. CD4+ helper T cells favour the
      generation of high-affinity antibodies that are effective against blood stages
      and they are necessary to establish immunological memory. The intrahepatic stage
      of infection can be eliminated by specific CD8+ cytotoxic T cells (CTL).
      Cytokines secreted by CD4+ T cells may also contribute to liver stage immunity.
      Evolution has selected varied mechanisms in pathogens to avoid recognition by T
      cells. T cells recognize foreign epitopes as complexes with host major
      histocompatibility (MHC) molecules. Thus, a simple form of evasion is to mutate
      amino acid residues which allow binding to an MHC allele. Recently, more
      sophisticated forms of polymorphic evasion have been described. In altered
      peptide ligand (APL) antagonism, the concurrent presentation of particular
      closely related epitope variants can prevent memory T cell effector functions
      such as cytotoxicity, lymphokine production and proliferation. In immune
      interference, the effect of the concurrent presentation of such related epitope
      variants can go a step further and prevent the induction of memory T cells from
      naive precursors. The analysis of immune responses to a protein of P. falciparum,
      the circumsporozoite protein (CSP), indicates that the malaria parasite may
      utilize these evasion strategies.

PMID- 9571692
TI  - Role of the immune response induced by superantigens in the pathogenesis of
      microbial infections.
AB  - Superantigens (SAgs) are microbial proteins which have potent effects on the
      immune system. They are presented by major histocompatibility complex (MHC) class
      II molecules and interact with a large number of T cells expressing specific T
      cell receptor V beta domains. Encounter of a SAg leads initially to the
      stimulation and subsequently to the clonal deletion of reactive T cells. SAgs are
      expressed by a wide variety of microorganisms which use them to exploit the
      immune system to their own advantage. Bacterial SAgs are exotoxins which are
      linked to several diseases in humans and animals. A classical example is the
      toxic shock syndrome in which the massive release of cytokines by SAg-reactive
      cells is thought to play a major pathogenic role. The best characterized viral
      SAg is encoded by mouse mammary tumour virus (MMTV) and has proved to have a
      major influence on the viral life cycle by dramatically increasing the efficiency
      of viral infection. In this paper, we review the general properties of SAgs and
      discuss the different types of microorganisms which produce these molecules, with
      a particular emphasis on the role played by the SAg-induced immune response in
      the course of microbial infections.

PMID- 9571693
TI  - Macrophage apoptosis in microbial infections.
AB  - Upon infection with a pathogen, eukaryotic cells can undergo programmed cell
      death as an ultimate response. Therefore, modulation of apoptosis is often a
      prerequisite to establish a host-pathogen relationship. Some pathogens kill
      macrophages by inducing apoptosis and thus overcome the microbicidal arsenal of
      the phagocyte. Apoptotic macrophages, on the other hand, can elicit an
      inflammation by secretion of proinflammatory cytokines. Shigella flexneri, the
      aetiological agent of bacillary dysentery, induces apoptosis in macrophages
      which, in agony, specifically release mature interleukin-1 beta (IL-1 beta). This
      cytokine attracts neutrophils (PMN) to the site of infection resulting in the
      massive colonic inflammation characteristic of bacillary dysentery. Shigellosis
      represents a paradigm of a proinflammatory apoptosis in a bacterial infection.
      The molecular link between apoptosis and inflammation is interleukin-1 beta
      converting enzyme (ICE) which is activated during macrophage apoptosis and binds
      to IpaB, a secreted Shigella protein.

PMID- 9571694
TI  - Virus encoded cytokines and cytokine receptors.
AB  - In order to replicate efficiently within the host, viruses have evolved multiple
      strategies to evade the host's immune system. In many cases viruses have actually
      hijacked various components of the host's immune system to ensure their own
      survival. One such strategy is the expression of virus encoded cytokines and
      cytokine receptors. Members of the poxvirus and herpesvirus families have been
      particularly successful with this strategy. The study of virus survival
      strategies provides important information regarding both virus biology as well as
      information about the immune system itself.

PMID- 9571695
TI  - Production of an interferon-gamma homologue by an intestinal nematode:
      functionally significant or interesting artefact?
AB  - Chronic infection is a prominent feature of many intestinal nematode infections
      in man and animals. It is also clear that in such situations host immunity is
      activated but is unable to induce a protective response. A great deal of work has
      shown that genetic control of host immunity contributes to the variation in worm
      burdens often observed in the field. There is increasing appreciation, however,
      of the capability of infectious agents themselves to modulate the host immune
      response and potentiate their own survival. Using an immunologically well defined
      model of intestinal nematode infection in mice (Trichuris muris) we have shown
      that parasite derived molecules share cross reactive epitopes with the host
      cytokine interferon-gamma using cytokine specific monoclonal antibodies in ELISA,
      Western blotting and immunoprecipitation assays. Furthermore, the parasite
      molecules can be shown to bind to the interferon-gamma receptor and induce change
      in lymphoid cells similar to those induced by murine interferon-gamma. The
      functional activity of the molecule in vivo remains to be determined. Previous
      studies have established that interferon-gamma is critical for progression to
      chronic T. muris infection in mice and, therefore, it raises the distinct
      possibility that the production of an interferon-gamma homologue by the worm may
      be one mechanism whereby the parasite is able to interfere with the regulation of
      the host immune response and potentiate its own survival.

PMID- 9571696
TI  - Cytokine induction and exploitation in schistosome infections.
AB  - Schistosome parasites, despite being multicellular organisms several millimetres
      in length, can survive in the bloodstream of mammalian hosts for decades. The
      remarkable and complex adaptation exemplified in the host-parasite relationship
      in schistosomiasis may include not only immune evasion by the parasite, but also
      immune exploitation. While the developmental and adult stages of the parasite are
      by and large invisible to the immune response, the parasite egg induces a
      granulomatous reaction which not only protects the host from a diffusible
      parasite toxin, but also is required for normal transmission of parasite eggs
      from the host to the external environment. Other possible mechanisms of immune
      exploitation by schistosomes are discussed including skewing of cytokine
      responses, effects of cytokines on worm fecundity, exploitation of endothelial
      cell adherence, and induction of IgE.

PMID- 9571697
TI  - A role for granulomatous inflammation in the transmission of infectious disease:
      schistosomiasis and tuberculosis.
AB  - The relationship between cell-mediated granulomatous inflammation and
      transmission of disease in schistosomiasis and tuberculosis has been explored. In
      2 experiments involving Schistosoma mansoni-infected normal and T cell-deprived
      mice, and infected deprived mice that had been variously reconstituted with
      immune or normal lymphocytes or immune serum, there was a significant positive
      numerical correlation between mean liver granuloma diameters and faecal egg
      counts in individual animals. Lymphocytes from donors with recently patent
      infections were more active than cells from chronically infected or uninfected
      donors in reconstituting egg excretion rates in deprived recipients, and
      mesenteric lymph node (MLN) cells were more active than spleen cells. Modulation
      of granulomatous activity with increasing chronicity of infection in the donors,
      resulting in a decrease in granuloma size around freshly produced tissue-bound
      eggs, was paralleled by a waning of the capacity of transferred lymph node cells
      to reconstitute egg excretion in the recipients. Serum taken from chronically
      infected donor mice over the same period and transferred to infected deprived
      recipients became more active in enhancing egg excretion in the recipients as the
      cell-mediated activity declined. A recent study in Kenya has found that S.
      mansoni-infected patients with concurrent human immunodeficiency virus (HIV)
      infection excrete fewer eggs than patients exposed to the same levels of
      schistosome infection, but who are not HIV-infected, thus indicating that
      schistosome egg excretion in humans is also immune-dependent. Attention is drawn
      to an apparently parallel situation in human tuberculosis, another pathogen which
      induces a cell-mediated granulomatous immune response. Several studies have shown
      that patients with tuberculosis who are also HIV-seropositive tend to have fewer
      tubercle bacilli detectable in their saliva than those with tuberculosis, but who
      are HIV-negative. This discrepancy, associated with differences in lung pathology
      in HIV-positive patients, suggests that in tuberculosis immune cell-mediated
      granulomatous inflammation causes the destruction of host tissue in a manner
      which facilitates onward transmission of the bacterial pathogen.

PMID- 9571698
TI  - Enhancing antibodies in HIV infection.
AB  - The author has summarized the history of discovery, the mechanism and the
      clinical significance of antibody-dependent enhancement (ADE) of HIV infection.
      ADE has two major forms: (a) complement-mediated antibody-dependent enhancement
      (C-ADE) and (b) complement-independent Fc receptor-dependent ADE (FcR-ADE). The
      most important epitope responsible for the development of C-ADE-mediating
      antibodies is present in the immunodominant region of gp41 while antibodies
      mediating FcR-ADE react mainly with V3 loop of gp120. There are at least three
      fundamentally different hypotheses for the explanation of ADE in vitro: (a)
      increased adhesion of HIV -antibody-(complement) complexes to FcR or complement
      receptor carrying cells; (b) facilitation of HIV-target cell fusion by complement
      fragment deposited on the HIV-virions and (c) complement activation products may
      have a non-specific stimulatory effect on target cells resulting in enhanced
      virus production. FcR-ADE and C-ADE have been measured in vitro mostly by using
      FcR-carrying and complement receptor-carrying cell lines, respectively; no
      efforts have been made to standardize these methods. Several data support the
      possible clinical significance of FcR-ADE and C-ADE: (a) Cross-sectional and
      longitudinal studies indicate a correlation between the amounts of FcR-ADE and C
      ADE-mediating antibodies and clinical, immunological and virological progression
      of the HIV-disease; (b) ADE may facilitate maternal-infant HIV-1 transmission;
      (c) According to experiments in animal models, ADE are present and may modify the
      course of SIV (simian immunodeficiency) infection as well. The author raises a
      new hypothesis on the mechanism of the in vivo effect of C-ADE. According to the
      hypothesis, C-ADE-mediating antibodies exert their effect through enhancement of
      HIV propagation and consequent facilitation of the progression of HIV disease.
      Finally, according to observations from animal experiments and human clinical
      trials it cannot be excluded that ADE-mediating antibodies may develop, diminish
      the beneficial effect or may be harmful in volunteers vaccinated with HIV-1
      candidate vaccines.

PMID- 9571699
TI  - Immunological enhancement of breast cancer.
AB  - Breast cancer is a complex disease. Its aetiology is multifactorial, its period
      of development can span decades, and its clinical course is highly variable.
      Evaluation of the role of the immune response in either the development or
      control of breast cancer is also complex. Nevertheless, there is substantial
      information that in this disease, the immune response is not a host defence
      reaction and may even serve to facilitate cancer development. This evidence comes
      from a variety of sources including clinical-pathological investigations in women
      that show a correlation between the intensity of lymphocytic infiltration into
      the tumour mass with poor prognosis, studies in breast cancer patients that
      demonstrate a similar correlation between delayed hypersensitivity reactivity or
      in vitro assays of immune reactivity to tumour cell membranes or non-specific
      antigens and poor prognosis, and analyses of cancer incidence in chronically
      immunosuppressed, kidney transplant recipients who develop an unexpectedly low
      incidence of breast cancer. The overall conclusions from these human studies are
      corroborated by observations in mouse mammary tumour models that also demonstrate
      immune enhancement of breast cell proliferation in vitro and of breast cancer
      development in vivo. Potential mechanisms for these effects include production,
      by inflammatory cell infiltrates, of direct or indirect modulators of breast cell
      growth, e.g. cytokines, peptide or steroid hormones, enzymes involved in steroid
      metabolism, as well as of antibodies to growth factors or their receptors. These
      immune facilitatory mechanisms must be overcome if immune-based therapies are to
      be applied successfully in breast cancer.

PMID- 9571700
TI  - Mathematical models of parasite responses to host immune defences.
AB  - We examine the evolution of microparasites in response to the immune system of
      vertebrate hosts. We first describe a simple model for an acute infection. This
      model suggests that the within-host dynamics of the microparasite will be a
      'race' between parasite multiplication and a clonally expanding response by the
      host immune system, resulting either in immune-mediated clearance or host death.
      In this very simple model, in which there is only a single parasite and host
      genotype, maximum transmission is obtained by parasites with intermediate rates
      of growth (and virulence). We examine how these predictions depend on key
      assumptions about the parasite and the host, and consider how this model may be
      expanded to incorporate the effect of additional complexities such as host
      parasite co-evolution, host polymorphism, and multiple infections.

PMID- 9571701
TI  - Parasite immune evasion and exploitation: reflections and projections.
AB  - Recent developments in parasite immune evasion and exploitation are reviewed with
      special reference to the papers presented in this volume. Parasites, broadly
      defined, of animals with good immune responses have evolved many strategies that
      adapt them to survive and reproduce. These strategies may be passive, or may
      involve active intervention with host immune regulation, and can be categorized
      as immune evasion, immune exploitation and molecular piracy. The concept of
      immune evasion began with Paul Ehrlich's demonstration of antigenic variation in
      African trypanosomes and was reinforced by later ideas on molecular mimicry.
      Molecular mimicry is updated in the light of recent discoveries about degeneracy
      and plasticity of TCR/MHC-peptide recognition. Possible connections between two
      of its postulated consequences, evasion and autoimmunity, are discussed. Another
      putative consequence of molecular mimicry, host antigenic polymorphism, is also
      updated. The concept of exploitation of host immune responses by parasites has
      been reinforced by new data on its first known examples, especially the immune
      dependence of schistosome egg excretion. Newer examples include use of host
      cytokines as parasite growth factors, virokines, viroreceptors and helminth
      pseudocytokines. Finally, questions of host gene capture by viruses and possible
      horizontal gene transfer between host and parasite mediated by retroviruses are
      examined. The latter is compared with molecular conservation as a source of
      molecular mimicry and other aspects of host--parasite coevolution.

PMID- 9571702
TI  - Dietary macro- and micronutrient requirements of endurance athletes.

PMID- 9571703
TI  - Free radicals, exercise and antioxidant supplementation.
AB  - Although conflicting data exist, the preponderance of available information
      suggests that physical exercise promotes an increase in free-radical generation.
      However, few studies have actually measured exercise-induced free radicals
      directly, primarily because of a lack of sophisticated methodologies to measure
      this phenomenon. Instead, researchers have relied heavily on the measurement of
      lipid peroxidation as the principal indicator of exercise-induced free radicals.
      It should be noted that free radicals can also alter and inactivate enzyme
      complexes, damage DNA and RNA, and promote mutations and cancer, among other
      activities. However, there have been few reported studies dealing with exercise
      and oxidant stress which have measured these outcomes. It should also be noted
      that free-radical species are continuously produced in the human body, and that
      some have beneficial effects (Arouma, 1994), notably as a part of the body's
      natural immune system. It is not presently known if long-term ingestion of
      antioxidant compounds will affect these positive aspects of free-radical
      generation. The preponderance of available evidence suggests that antioxidant
      supplementation, particularly with the vitamins C and E, has favourable effects
      on markers of lipid peroxidation following exercise. Although the physiological
      implications of these effects remain to be elucidated, the prudent use of an
      antioxidant supplement can provide insurance against a suboptimal diet and/or the
      elevated demands of physical activity. Future research may uncover additional
      nutritional antioxidants that can benefit the physically-active individual.
      Numerous additional questions regarding the antioxidant needs for physical
      activity remain to be answered. Little is known about the needs of physically
      active women, particularly those who habitually consume an energy-restricted
      diet, or the effects of monthly menstrual blood loss (coupled with exercise) on
      antioxidant requirements. The needs of the 'weekend warrior' (an individual who
      participates in strenuous activity sporadically) v. those of the habitual
      exerciser have not been addressed adequately. The needs of the ageing athlete are
      largely unknown; a study by Meydani et al. (1993) suggested that elderly,
      physically-active people can benefit from antioxidant supplementation more than
      their younger counterparts, but follow-up studies have not been reported to-date.
      Dietary issues also need to be addressed. How much supplementation is too much,
      and can chronically-elevated antioxidant intakes have an adverse impact on the
      positive effects of free radicals in living systems? Does a high-carbohydrate
      diet raise antioxidant needs, particularly of the fat-soluble vitamin E? Does a
      high polyunsaturated fat intake, or increased Fe intake affect needs? Obviously,
      there are a number of issues regarding the antioxidant needs of the physically
      active individual that need to be elucidated. Future research utilizing newer,
      more sophisticated methodologies should provide answers to many of these
      questions.

PMID- 9571705
TI  - Influence of diet on the metabolic responses to exercise.
AB  - The relationship between dietary intake and skeletal-muscle exercise metabolism
      is central to the interests of exercise physiologists. This area has been
      examined experimentally for over 100 years. Classic studies with male subjects
      demonstrated the importance of dietary CHO in maximizing muscle and liver
      glycogen stores in an attempt to optimize exercise performance. CHO becomes the
      predominant fuel for exercise at power outputs above 50-60% Vo2max and its
      availability limits prolonged aerobic exercise at intensities corresponding to 65
      85% VO2max. Recent information suggests that female subjects are less able to
      maximize muscle glycogen stores through dietary means. Contemporary studies have
      documented in more detail the greater reliance on CHO metabolism following a high
      CHO-low-fat and -protein diet and the greater reliance on fat metabolism
      following a low-CHO-high-fat and protein diet. More emphasis on documenting key
      enzymic changes in the energy-producing pathways and transport proteins has
      appeared. However, very little is known regarding the mechanisms that induce
      these changes over the short or long term in human skeletal muscle. For example,
      the central role of PDH activity in the selection of intramuscular fuel during
      exercise and the role of carnitine palmitoyltransferase 1 in the entry of NEFA
      into the mitochondria, and the effects of diet on these enzymes has received
      little attention to date. Many research studies have examined extreme diet
      variations (% total energy; > 85% CHO v. < 5-10% CHO) for short periods of time
      in an attempt to maximize diet-induced alterations and study the mechanisms
      responsible for the changes. However, future studies will need to examine less
      severe diet alterations for longer periods of time that more accurately reflect
      what the normal population might experience, such as a diet containing (% total
      energy) 60 fat, 20 CHO, 20 protein or the recently popular diet with (% total
      energy) 30 fat, 40 CHO, 30 protein.

PMID- 9571704
TI  - The sports drink as a functional food: formulations for successful performance.

PMID- 9571706
TI  - Amino acid metabolism, branched-chain amino acid feeding and brain monoamine
      function.
AB  - Although fatigue during prolonged exercise has traditionally been associated with
      peripheral factors relating to muscle metabolism, such as the depletion of muscle
      glycogen, more recent research has generated a renewed interest in amino acid
      metabolism per se and in the role of amino acids as precursors of brain
      neurotransmitter function. The concept of a 'central fatigue hypothesis' has done
      much to stimulate scientists to explore the functional role of the brain and CNS
      in the aetiology of the fatigue process. The concept has also generated a number
      of testable hypotheses by which it is possible to examine how the 'central'
      component of fatigue may act. The present review has attempted to bring together
      the current research in this area. There is good reason to believe that
      nutritional intervention may play an important role in relation to fatigue
      residing within the brain and CNS. Although an exciting possibility exists that
      nutritional manipulation may affect brain neurochemistry and ultimately sports
      performance, the experimental evidence to support this claim is, as yet,
      equivocal. A greater understanding of amino acid metabolism and, in particular,
      amino acid transport, will greatly improve future experimental designs used to
      test the efficacy of nutritional manipulation of amino acids and their effect on
      the central component of the fatigue process.

PMID- 9571707
TI  - Nutrition, exercise and the immune system.

PMID- 9571708
TI  - Use of endogenous carbohydrate and fat as fuels during exercise.

PMID- 9571709
TI  - The nutritional demands of very prolonged exercise in man.

PMID- 9571710
TI  - Exercise and postprandial lipid metabolism.

PMID- 9571711
TI  - Effect of high-fat diets on exercise performance.

PMID- 9571712
TI  - The relationship between physical activity and food intake.

PMID- 9571713
TI  - Exercise and obesity.

PMID- 9571714
TI  - Exercise prescription for weight management.
AB  - The debate surrounding the level of intensity of exercise that is best for health
      improvement has potentially clouded the issue of optimal exercise prescription
      for weight management. Low-intensity activity is potentially superior to moderate
      to high intensity for improving metabolic risk factors, and accumulated small
      bouts of physical activity are as effective to this end as single longer bouts,
      as long as the overall volume of energy expenditure is equivalent. What should
      not be forgotten however, is that for weight-loss it is the total volume of
      energy expended that will dictate the size of the energy deficit imposed, not the
      composition of the exercise per se. Exercise prescription for weight management
      is a conundrum. Whilst it is the total volume of energy expended that will
      dictate the magnitude of weight lost, not the composition of the exercise per se,
      it is the nature of the exercise prescription that will dictate the long-term
      success of an exercise programme. It is how well the exercise prescription is
      individualized that influences tolerance of and interest in the programme and,
      thus, the adherence to it in the long term.

PMID- 9571715
TI  - Maternal nutrition, placental growth and fetal programming.

PMID- 9571716
TI  - Glucocorticoids and the preparation for life after birth: are there long-term
      consequences of the life insurance?

PMID- 9571717
TI  - Fetal origins of cardiovascular risk: evidence from studies in children.

PMID- 9571718
TI  - Reproductive outcomes in women prenatally exposed to undernutrition: a review of
      findings from the Dutch famine birth cohort.

PMID- 9571719
TI  - Combating micronutrient deficiencies: problems and perspectives.

PMID- 9571720
TI  - The anthropometric status of schoolchildren in five countries in the partnership
      for child development.

PMID- 9571721
TI  - Vitamin A and public health: challenges for the next decade.

PMID- 9571722
TI  - Nutrition interventions to reduce diarrhoea morbidity and mortality.

PMID- 9571723
TI  - The in-hospital Utstein style: use in reporting outcome from cardiac arrest in
      Middlemore Hospital 1995-1996.
AB  - The in-hospital Utstein Style was published in April 1997. This new format is
      used to present the outcome of in-hospital cardiac arrest in Middlemore Hospital,
      Auckland, NZ, between June 1995 and June 1996. The in-hospital Utstein Style was
      generally easy to follow, but there were several areas where adjustments may be
      of benefit. The study shows that there were 140 true arrest calls during this
      period, with 133 attempted resuscitations. Forty-seven patients had ROSC greater
      than 24 h, 35 were discharged alive and 30 were alive at 1 year. Of these 30
      survivors, 27 had a Cerebral Performance Category of 1.

PMID- 9571724
TI  - Advanced cardiac life support events in a community hospital and their outcome:
      evaluation of actual arrests.
AB  - To evaluate resuscitation efforts for patients with cardiac and/or pulmonary
      arrest in our hospital a retrospective study was conducted and compared with
      available data from other community teaching hospitals. Records of 131
      consecutive patients of ages 16-98 who received resuscitation according to
      Advanced Cardiac Life Support protocols were reviewed. Short-term survival
      (return of spontaneous circulation) and discharge-from-the hospital survival were
      measured. Nineteen patients (15%) were excluded from the study because the
      information recorded on the code record sheet was insufficient. Overall short
      term survival rate was 34.8%. Resuscitations in the Emergency Room were evaluated
      separately, because most of them were initiated outside of the hospital. Their
      short-term survival was 14%, but none of them survived to be discharged. Out of
      69 inpatient resuscitative efforts, 33 were successful (47.8%). Of these 33 nine
      (13.0%) left the hospital. The rest expired during the same hospitalization.
      Short-term survival for patients after coronary artery bypass graft surgery was
      60% (6 of 10) and 30% (3 of 10) were discharged home. Forty percent of official
      code records were incomplete. We concluded that better education and more
      emphasis on record-keeping are mandatory, with the main burden falling upon the
      nurse in charge to have received more precise instruction. Contrary to published
      data, women did not have a better survival than men (P > 0.05). There was no
      difference in outcomes between resident physician directed codes compared to
      attending physician directed codes (P > 0.05). The mean age of inpatient short
      term survivors was 69.0 (+/- 13.2) years and that of non-survivors 69.8 (+/-
      15.7) years (P > 0.05). Post-bypass surgery patients had a better survival than
      non-surgical patients, but the difference was significant (P > 0.05). Survival in
      our hospital was comparable to one hospital and worse than another (34.8% vs.
      39.6% or 63.0%). Despite success, prognosis after arrest remain poor.

PMID- 9571725
TI  - The role of inhalation rewarming in the early management of hypothermia.
AB  - OBJECTIVE: To evaluate the effectiveness of inhalation rewarming in early
      resuscitative efforts for hypothermic victims. DATA SOURCES: Search of MEDLINE
      and manual retrieval using the terms hypothermia, resuscitation, inhalation and
      treatment. All articles and papers published within the last 5 years were
      searched. Earlier literature was also included if considered vital to documenting
      the scientific basis and rationale for using airway rewarming. STUDY SELECTION:
      Letters to the editor, review articles, case reports and original research were
      included in this review. Material was considered for inclusion if it contributed
      generally to the understanding of the role of inhalation rewarming in the
      stabilization or treatment of accidental hypothermia. RESULTS: The literature
      reported many instances in which inhalation rewarming appeared to contribute to a
      successful outcome during hypothermic resuscitative efforts. The maximum
      contribution that inhalation rewarming provides to overall core rewarming does
      not appear to endorse it as a sole method of core rewarming. CONCLUSIONS: The
      safety and efficacy of inhalation rewarming suggest that it is a viable adjunct
      of treatment during hypothermic resuscitation. Its routine use may be more
      appropriate for a field rescue situation where more advanced rewarming modalities
      may not be available or practicable. Also, its primary value may be to minimize
      further core temperature loss during early management of accidental hypothermia.

PMID- 9571726
TI  - Selective neurological recovery or dissociated cardiac death--to be or not to be-
      during cardiopulmonary resuscitation.
AB  - Of 111 victims of circulatory arrest, 93 (84%) retained or regained some brain
      function during the resuscitation process. Twenty-six of these (24%) did not have
      spontaneous circulation restored, and a further 18 (16%) were left in cardiogenic
      shock and died within 24 h. Bradyarrhythmia or asystole during the resuscitation
      efforts or prolonged resuscitative attempts beyond 20 min were related to the
      irreversible failure of heart pump function. Individuals developing either this
      type of 'dissociated cardiac death' or cardiogenic shock could not be identified
      prior to resuscitation by the cause of the arrest nor by the initial cardiac
      arrhythmia. 'Dissociated cardiac death' and cardiogenic shock are major problems
      in cardiopulmonary resuscitation. A code of practice is urgently needed.

PMID- 9571727
TI  - The natural course of neurological recovery following cardiopulmonary
      resuscitation.
AB  - In 231 patients resuscitated from circulatory arrest of cardiovascular or
      pulmonary aetiology brain recovery was evaluated by serial neurological and EEG
      examinations for up to 1 year. One-hundred and sixteen patients never regained
      consciousness; 115 patients awakened within 30 days, and 40 eventually recovered
      completely within 90 days. Patients who had electrocortical activity recorded by
      the immediate post-resuscitation EEG (N = 106), and patients initially without
      such activity (N=125) pursued the same course of recovery: during
      unconsciousness, interrelated EEG and neurological findings featured a phase of
      intermittent cortical activity with postural or stereotypic motor responses
      followed by a phase of continuous cortical activity with sequential appearances
      of delta, theta, and alpha activities on EEG accompanied by stereotypic or
      defensive motor responses. After awakening, the sequential return of motor,
      sensory, and mental faculties differentiated an early phase of severe disability
      with orientating eye movements and a bilateral Babinski response from the phase
      of moderate disability featured by speech, locomotor functions, ability to cope
      with personal necessities and orientation as to personal data, and a normal
      plantar response. Finally, orientation as to time, place and role of other
      persons, and retention and recall, defined the phase of slight/no disability.
      Abnormal courses were identified by incomplete EEG and neurological recoveries or
      by the appearance of spikes and sharpwaves in the EEG, or by losses of function.

PMID- 9571729
TI  - Cardiopulmonary resuscitation: a review for clinicians.
AB  - Attempts at cardiopulmonary resuscitation (CPR) date from antiquity, but it is
      only in the last 50 years that a scientifically-based methodology has been
      developed. External chest compressions is the standard method for managing
      circulatory arrest, however, numerous alterations of this technique have been
      proposed in attempts to improve outcome from CPR. Defibrillation is the single
      most important therapy for the management of ventricular fibrillation or
      pulseless ventricular tachycardia. Adrenergic agents used to improve myocardial
      and cerebral perfusion are also the subject of considerable investigation with
      new agents entering clinical study. This paper reviews the history, current
      techniques and pharmacotherapy as well as controversial issues in the management
      of patients with cardiac arrest.

PMID- 9571728
TI  - Effect of different compression--decompression cycles on haemodynamics during ACD
      CPR in pigs.
AB  - The haemodynamic effects of variations in the relative duration of the
      compression and active decompression (4 cm/2 cm) during active compression
      decompression cardiopulmonary resuscitation (ACD-CPR), 30/70, 50/50 and 70/30,
      were tested in a randomized cross-over design during ventricular fibrillation in
      seven anaesthetized pigs (17-23 kg) using an automatic hydraulic chest
      compression-decompression device. Duty cycles of 50/50 and 70/30 gave
      significantly higher values than 30/70 for mean carotid blood flow (32 and 36 vs.
      21 ml min-1, transit time flow probe, cerebral blood flow (30 and 34 vs. 19,
      radionuclide microspheres), mean aortic pressure (35 and 41 vs. 29 mmHg) and mean
      right atrial pressure (24 and 33 vs. 16 mmHg). A higher mean aortic, mean right
      atrial and mean left ventricular pressure for 70/30 were the only significant
      differences between 50/50 and 70/30. There were no differences in myocardial
      blood flow (radionuclide microspheres) or coronary perfusion pressure (CPP,
      aortic-right atrial pressure) between the three different duty cycles. CPP was
      positive in both the early and late compression period and during the whole
      decompression period. The expired CO2 was significantly higher with 70/30 than
      30/70 during the compression phase of ACD-CPR. Beyond that no significant
      differences in the expired CO2 levels were observed. In conclusion a reduction of
      the compression period to 30% during ACD-CPR reduced the cerebral circulation,
      the mean aortic and right atrial pressures with no effect on the myocardial blood
      flow of varying the compression-decompression cycle.

PMID- 9571730
TI  - Rhodococcus equi pneumonia in patients infected with the human immunodeficiency
      virus. Report of 2 cases and review of the literature.
AB  - Rhodococcus equi is a cause of lung infection in immunosuppressed hosts. Since
      the start of the HIV epidemic, 76 cases of R. equi lung infection (MEDLINE 1985
      96) affecting this population have been described. We report 2 additional cases
      and review the clinical data, radiological findings, treatment and outcome of
      these 78 patients. The mean age of these patients was 33 y; 69 were male. 71 met
      the criteria for AIDS (CDC 1993). Fever and cough were the presenting complaints
      in the majority of patients (84.3%). A single cavitary lung lesion in the upper
      lobes was the most common radiological finding (57.7%), although multiple
      cavitations, alveolar infiltrates and pleural effusion were also found. Treatment
      usually was based on synergistic antibiotic combinations for a long period of
      time determined on an individual basis. Surgery was performed only in 11
      patients. Death attributable directly to R. equi infection is low (15.4%),
      however only half of the patients (53.8%) were completely cured. We conclude that
      R. equi infection should be strongly considered in any HIV patient who presents
      with cavitary lesions in the lung, especially if mycobacteria are not identified.
      Treatment must be based on synergistic antibiotic combinations, and surgery
      relegated to cases of chronic single cavitary lesions not responding to
      antibiotics.

PMID- 9571731
TI  - The influence of cytomegalovirus on the natural history of HIV infection:
      evidence of rapid course of HIV infection in HIV-positive patients infected with
      cytomegalovirus.
AB  - We studied a cohort of 299 HIV-positive individuals with known date of
      seroconversion to evaluate the role of Cytomegalovirus (CMV) in the natural
      history of HIV. The study population consisted of 236 initially CMV-positive
      patients, 55 CMV-negative subjects and 8 CMV seroconverters. The study endpoints
      were the decline to CD4+ < 200 x 10(6) cells/l, AIDS, and death. The cumulative
      risk of CMV disease and the survival after CMV disease were also investigated. At
      intake, there was no inter-group difference in sex, age, risk behaviours, history
      of hairy leucoplakia or herpes zoster and antiretroviral treatment. During the
      follow-up, 108 patients fell below 200 CD4+ x 10(6) cells/l, 72 developed AIDS
      and 63 died. Twenty-one subjects had CMV disease. The cumulative incidence of CMV
      disease in the cohort was 18.9%, and 23.3% within 8 and 9 years for the initially
      CMV-positive patients and 33.3% and 66.7% for the CMV seroconverters (log-rank
      test: p = 0.101). The median survival after CMV disease was 153 days (range: 28
      855, interquartile range: 261), with a cumulative survival of 45.1%, 16.9% and
      4.3% within 6, 12 and 18 months, respectively. On Cox's regression, the acute HIV
      seroconversion was an independent predictor of each endpoint, history of hairy
      leucoplakia or herpes zoster being associated only with CD4+ cell decline.
      Baseline CMV seropositivity was related to short survival (p = 0.037) and 2 x 2
      inter-group comparison showed that older individuals with sexually acquired HIV
      who seroconverted to CMV had higher rates of progression to the study endpoints.
      Our data suggest that CMV infection influences the natural history of HIV disease
      and that CMV disease strongly affects the survival of the HIV-positive patients.

PMID- 9571732
TI  - Haemolysis complicating acute viral hepatitis in patients with normal or
      deficient glucose-6-phosphate dehydrogenase activity.
AB  - Haemolytic anaemia as a complication of acute hepatitis has been reported in up
      to 23% of patients. However, the incidence may rise up to 70-87% in patients who
      have glucose-6-phosphate dehydrogenase (G6PD) deficiency. Massive intravascular
      haemolysis with renal failure, hepatic encephalopathy and even death have been
      reported. In our retrospective study of patients with acute viral hepatitis, the
      overall incidence of acute haemolysis was 4% (17/434). Only 53% (9/17) of them
      had G6PD deficiency. Patients with acute haemolysis had a significantly higher
      peak bilirubin level and required more prolonged hospitalization. Since hepatitis
      A virus vaccination, unlike hepatitis B virus vaccination, is not yet recommended
      for routine immunization, we suggest subjects who are G6PD-deficient should be
      vaccinated against hepatitis A. In endemic areas of hepatitis A virus infection,
      universal immunization remains the definitive answer.

PMID- 9571733
TI  - Carriage of multiresistant Streptococcus pneumoniae among children attending day
      care centres in the Stockholm area.
AB  - To determine the prevalence of the asymptomatic carriage of drug-resistant
      Streptococcus pneumoniae (DRSP) by children attending day-care centres in the
      Stockholm area, nasopharyngeal swabs were cultured from 1129 children and 308 day
      care personnel in 36 day-care centres during a 3-week period, from March to April
      1995. Approximately 36% of the children were asymptomatic carriers of S.
      pneumoniae sensitive to penicillin and other antibiotics. The highest prevalence
      of nasopharyngeal carriage was found in the 2-year-old group (50%), whereas among
      the 4-year-old children colonization was observed in 42%, and among the 7-year
      old children 21% were asymptomatic carriers of penicillin-sensitive S.
      pneumoniae. In 2 day-care centres, 4 and 5 children, respectively, were found to
      have DRSP strains in the nasopharynx. The same serotype of DRSP strain was found
      among the children attending the same day-care centre. During the same period,
      none of the staff were found to harbour DRSP in the nasopharynx, but 3% were
      asymptomatic carriers of penicillin-sensitive S. pneumoniae. The patterns of
      nasopharyngeal colonization by Haemophilus influenzae, Moraxella catarrhalis and
      Group A streptococci were also studied in 635 children during the same period.
      42% of the nasal cultures yielded Moraxella, 32% H. influenzae and 2%
      Streptococcus pyogenes.

PMID- 9571734
TI  - Antibiotic resistance in Streptococcus pneumoniae, Haemophilus influenzae and
      Streptococcus pyogenes in respiratory tract infections in outpatients.
AB  - Sensitivity patterns of Streptococcus pneumoniae, Haemophilus influenzae and
      Streptococcus pyogenes were studied prospectively in an outpatient population
      seeking medical advice for respiratory tract infections (RTI) in the Southern
      parts of Stockholm. In total, 3,214 nasopharyngeal and 1,907 throat swabs were
      cultured during January-February 1996. 32% of the patients had received
      antibiotics during the previous year. Reduced penicillin sensitivity in S.
      pneumoniae was rare (1.3%) and only seen in patients treated with antibiotics
      during the previous 4 months. Beta-lactamase production in H. influenzae was
      found in 13.4% of patients who had been treated with antibiotics during the last
      4 months and in 7.9% of the others. No resistance (< 1%) to erythromycin was seen
      in S. pyogenes. In this population-based surveillance, the levels of resistance
      in common respiratory tract pathogens were thus low and correlated to previous
      antibiotic treatment. Strict indications for antibiotic treatment in
      uncomplicated RTI are advocated to maintain a low resistance rate. Penicillin is
      still the drug of choice in patients without frequent recurrences of RTI in a
      setting similar to the one studied.

PMID- 9571735
TI  - Enteropathogenic bacteria in migrating birds arriving in Sweden.
AB  - Birds have been thought to play a role in transmitting infectious agents like
      influenza, Borrelia and Salmonella. To investigate the role of migrating birds in
      the dispersal of enteropathogenic bacteria, stool samples from 151 wild birds (50
      gulls and 101 passerines) just entering Sweden from their winter grounds were
      analysed for Salmonella spp., Campylobacter spp. and EHEC O157:H7. The
      thermophilic isolated enteropathogens found were further analysed by
      antibiograms. Among the 50 gulls examined, we found 2 isolates of Salmonella
      typhimurium with multiple antibiotic resistance. Three isolates of C. jejuni were
      found in the 101 stool samples from passerines. We did not isolate EHEC O157:H7
      in any of the bird stools examined.

PMID- 9571736
TI  - Clinical manifestations and epidemiology of childhood tuberculosis in Stockholm
      1976-95.
AB  - 81 cases of tuberculosis infection (17) and disease (64), seen between 1977 and
      1995 at St Goran's Children's hospital, Stockholm, Sweden are reviewed. The
      incidence of tuberculosis disease increased from 1 to 6/10(5) children/y. The
      increase was due to immigration from high-prevalence countries, with an incidence
      of 20/10(5) in a partly segregated suburb. Most of the children were foreign
      born. Of the 31 0-4-y-old cases, 19 were born in Sweden, and 7 had received BCG
      vaccination. For Swedish-born children with Swedish-born parents, the incidence
      of tuberculosis disease remained stable at < 0.5. 50 patients were symptomatic
      when first seen (60% pulmonary tuberculosis, 8% military tuberculosis, 25%,
      cervical adenitis, 15% other extrapulmonary tuberculosis). There was 1 death, and
      in 2 children complicated tuberculosis courses. Side effects of drug therapy were
      seen in 5% of the children. In conclusion, tuberculosis remains an important
      differential diagnosis in children of immigrants from high-prevalence countries
      for at least 5 y after settlement in Sweden. The practice of delaying BCG
      vaccination of them until 6 months of age can be disputed.

PMID- 9571737
TI  - Mycobacterium fortuitum complex in Sweden during an 11-year period.
AB  - Records of patients have been retrospectively examined studied during an 11-y
      period, from whom Mycobacterium fortuitum or M. chelonae was isolated in Sweden.
      Respiratory isolates were obtained from 71 patients. Clinical information was
      accessible in 52, chest X-ray was pathological in 51, and 42 had underlying
      diseases. Four skin and 4 urine isolates were observed. Two cases of osteitis and
      2 bone marrow isolates of M. chelonae were found. One girl had a submandibular
      lymph node abscess with M. fortuitum. Of 2 HIV patients, 1 had positive blood
      cultures with M. fortuitum and the other positive sputum culture with M.
      chelonae. The broad spectrum of infections with M. fortuitum complex necessitates
      an integrated judgement of clinical and bacteriological data to determine the
      relevance of such isolates.

PMID- 9571738
TI  - Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV
      infected patients: progression from localized to systematic disease, German Aids
      Study Group (GASG/IDKF).
AB  - Our aim was to establish the frequency and the longitudinal pattern of MAC
      culture positivity in late stage HIV-infected patients. Two other aims were to
      analyse risk factors for progression from localized to systemic disease and the
      value of PCR diagnosis using blood specimens. A total of 107 patients were
      recruited to be followed for 32 weeks. Prior MAC treatment and CD4 >
      100/microliters were exclusion criteria. A total of 56 patients showed M. avium
      in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non
      sterile' specimens (stool, sputum) and urine progressed to systemic disease as
      determined by positive blood culture. Risk factors associated with this
      progression were a high symptom score at baseline, lymphadenopathy, anaemia, and
      low platelets. PCR was less sensitive than culture in detection of M. avium in
      blood specimens: Only 7/29 patients with positive blood cultures had a positive
      PCR at the same time. We conclude that symptomatic patients with advanced HIV
      infection have a high frequency of MAC detection. Progression from localized to
      systemic culture positivity is associated with risk factors. Early 'pre-emptive'
      therapy is discussed.

PMID- 9571739
TI  - Demonstration of Chlamydia pneumoniae in patients with chronic pharyngitis.
AB  - 12 patients with longstanding throat symptoms, who were also positive by PCR
      (polymerase chain reaction) for Chlamydia pneumoniae were selected for a
      longitudinal study to determine whether C. pneumoniae is an aetiological agent
      for chronic pharyngitis. Specimens for culture and PCR detection of C. pneumoniae
      were taken from the retropharyngeal wall and blood specimens were taken for
      serology. Biopsies were taken from the mucosal membrane of the retropharyngeal
      wall for histological and immunohistochemical studies. C. pneumoniae was cultured
      from 4 cases. 10 patients had specific humoral antibodies to C. pneumoniae and 9
      had high and increasing specific antibody titres to C. pneumoniae suggesting
      ongoing infection. The organism was demonstrated in the tissue from the
      retropharyngeal mucosal membrane by immunohistochemistry in 9 patients. The
      findings suggest that C. pneumoniae may be an aetiological agent for chronic
      pharyngitis.

PMID- 9571740
TI  - Pneumocystis carinii colonization in the absence of immunosuppression.
AB  - A prospective study was undertaken to evaluate the incidence and the course of
      Pneumocystis carinii colonization in immunocompetent patients with severe
      pulmonary diseases. A further perspective was to determine the diagnostic values
      of different detection methods. Bronchoalveolar lavage fluid samples from 77/838
      adult HIV-negative patients were examined by Diff-Quik stain, direct
      immunofluorescence test and polymerase chain reaction. All Diff-Quik stains were
      negative, but direct immunofluorescence tests and polymerase chain reactions were
      positive in the samples of 5 patients. The normal number of granulocytes and
      CD4+T- lymphocytes (median 810 cells/microliters) and normal values of
      immunoglobulins proved the relative competence of the immune systems of the 77
      patients. Although none of these patients received any agent effective against P.
      carinii, none developed a P. carinii pneumonia within a 120.5-d surveillance
      period. Nosocomial transmission could be excluded. As the colonization with P.
      carinii did not result in pneumonia in immunocompetent patients, clinically
      silent carriers have to be assumed. In non-AIDS patients, sensitive detection
      methods have to be used to identify colonized persons.

PMID- 9571741
TI  - Toxoplasmosis in Danish AIDS patients.
AB  - Infection with Toxoplasma gondii was studied in 600 patients with AIDS, diagnosed
      in the eastern part of Denmark from 1980 up to and including 1990. The median age
      was 38 years, and 223 (44%) had anti-T. gondii IgG antibodies. Of the patients
      seropositive to T. gondii 61 (27%) developed toxoplasma encephalitis (TE). Few
      patients received prophylactic treatment with sulfamethoxazole-trimetoprim. In
      total, 66 patients were diagnosed with TE. One had no serological test performed,
      and of the remaining 65, 4 (6%) had no anti-T. gondii IgG antibodies. The
      predictive value of a negative Sabin-Feldman dye test was 99%. The geometric mean
      dye test titer was higher in patients with TE than in patients without TE. Of the
      patients with TE 34% had serological reactivation of their T. gondii infection at
      the time of TE diagnosis, and 34% had detectable T. gondii-specific antibodies in
      the cerebrospinal fluid. Specific IgM antibodies were found to have little value
      in the diagnosis of TE, as only 3% had detectable IgM antibodies. Acute
      toxoplasmosis was the AIDS-defining diagnosis for 23 (35%) of the patients with
      TE. The median CD4 count at the time of TE was 30 x 10(6)/l, and the median
      survival time from diagnosis of TE was 9 months.

PMID- 9571742
TI  - Antibiotic therapy and outcome of monomicrobial gram-negative bacteraemia: a 3
      year population-based study.
AB  - Within the 3-y period 1992-94 a total of 815 episodes of monomicrobial
      bacteraemia caused by Enterobacteriaceae not including Salmonella were registered
      in the County of Northern Jutland. The 30-d case fatality rate was 24%, ranging
      from 21% for Enterobacter spp. (n = 43), 22% for E. coli (n = 577) to 32% for
      both Klebsiella spp. (n = 138) and a group of miscellaneous enterobacteria (n =
      57). In 16% of the bacteraemias, antibiotic treatment was not instituted before
      notification of positive blood cultures; in 9% empirical antibiotic treatment was
      inappropriate. Antibiotic regimens mainly included beta-lactams, ampicillin or
      mecillinam in combination with an aminoglycoside. The following factors were
      independently associated with case fatality: age > or = 75 y, high comorbidity
      index, admission to a medical ward or an intensive care unit, nosocomial
      acquisition, a source of infection outside the urinary tract or an undetermined
      focus, Klebsiella spp., inappropriate coverage or lack of antibiotic treatment
      before notification of positive blood culture. It is a matter of concern that in
      one-sixth of patients the physicians had not responded to the possibility of
      bacteraemia with institution of empirical antibiotic therapy.

PMID- 9571743
TI  - High incidence of antibiotic resistance among bacteria in 4 intensive care units
      at a university hospital in Sweden.
AB  - The frequency of antibiotic resistance among bacteria in 4 intensive care units
      (ICUs) at a university hospital in Sweden was investigated annually from 1993 to
      1996. An increase in ampicillin-resistant enterococci from 1993 to 1995 was seen
      which was due to a shift from Enterococcus faecalis to Enterococcus faecium.
      After a special infection control programme was instituted, the rate of
      ampicillin resistance among enterococci and the number of E. faecium isolates
      declined during 1996. The oxacillin resistance rates for Staphylococcus aureus
      were < or = 2%, while most of the coagulase-negative staphylococci (CNS) were
      oxacillin resistant. No vancomycin-resistant enterococci or staphylococci were
      seen. The ciprofloxacin resistance rate for CNS and Enterococci spp. were high.
      Relatively, high levels of resistance to cefotaxime and piperacillin/tazobactam
      among Enterobacter spp. were also seen. During 1995 and 1996 Pseudomonas
      aeruginosa showed increasing resistance to ceftazidime, ciprofloxacin and
      piperacillin/tazobactam. This was due to an outbreak among rather few patients.
      The overall resistance rates for Gram-negative bacteria were low for
      aminoglycosides and imipenem. From 1993 to 1996 the total antibiotic consumption
      decreased by 27% in the whole hospital and 16.5% in the ICUs. However, the
      reduced antibiotic consumption was paralleled with a 23% decrease in the total
      number of patients treated in the hospital from 1993 to 1996. In contrast there
      was an 11.5% increase in the number of ICU patients treated during this period.
      The conclusion is that all ICUs within a hospital should have a programme for 'on
      line' antibiotic resistance surveillance of drugs used in that unit in order to
      change the empiric treatment when there is an increase in antibiotic resistance.
      It is also important to survey the antibiotic consumption in the ICUs in order to
      avoid further selective pressure on bacteria showing increased resistance rates.

PMID- 9571744
TI  - In vitro activity of cefpirome against microorganisms isolated in haematology,
      oncology and intensive care units in Switzerland.
AB  - The in vitro activity of cefpirome, a new parenteral fourth-generation
      cephalosporin, was investigated in the 5 university hospitals of Switzerland, and
      compared to 9 other antibiotics mainly used in hospitals, such as ceftazidime,
      ceftriaxone, cefotaxime, piperacillin, imipenem, gentamicin, vancomycin,
      ciprofloxacin and ofloxacin. A total number of 992 strains collected only from
      intensive care units and haematology-oncology units were tested by microdilution
      according to NCCLS. Cefpirome showed an excellent activity against all
      Enterobacteriaceae (MIC90 = 4 mg/l), methicillin-susceptible staphylococci (MIC90
      = 1 mg/l), Streptococcus pneumoniae (MIC90 = 0.25 mg/l) and Haemophilus
      influenzae (MIC90 = 0.12 mg/l) isolates. Its activity was superior to that of
      third-generation cephalosporins against cephalosporinase-depressed mutants of
      Enterobacter cloacae and Citrobacter freundii isolates (MIC90 > 32 mg/l for third
      generation cephalosporins vs 4 mg/l for cefpirome). The MICs of cefpirome of 3
      strains of Klebsiella spp. with an extended-spectrum-beta-lactamase were lower
      (MIC90 = 2 mg/l) than those of third-generation cephalosporins (MICs90 > 32
      mg/l). Against Pseudomonas aeruginosa cefpirome was as active as ceftazidime. The
      activity of cefpirome was poor against methicillin-resistant staphylococci,
      enterococci and nosocomial Gram-negative bacteria such as Stenotrophomonas
      maltophilia.

PMID- 9571745
TI  - The influence of antimicrobial prophylaxis on the microbial and clinical findings
      in patients after autologous bone marrow transplantation.
AB  - The influence of a prophylactic regimen consisting of ciprofloxacin 250 mg bid,
      was examined by surveillance cultures from nose, throat, axilla, gingiva, exit
      site of central venous catheters, blood, rectum and urine of 60 patients
      undergoing autologous bone marrow transplantation during a 6-year period. None of
      the 60 patients developed any infectious with Gram-negative rods belonging to the
      Enterobacteriaceae, or deep fungal infections, during hospitalization. All
      patients were neutropenic. Febrile episodes were seen in all patients but 3. From
      13 patients, microorganisms in the blood, mostly nonhaemolytic streptococci
      (9/13), were cultured. Surveillance cultures did not predict later infections,
      but revealed the marked influence of the prophylactic antibiotics on the normal
      flora. Thus, mainly streptococci, coagulase-negative staphylococci and yeasts
      were cultured from the sites examined. It is concluded that the future objective
      of the microbiological surveillance should be restricted to monitoring the
      possible selection of drug-resistant microorganisms, and that routine cultures of
      blood and urine are unnecessary.

PMID- 9571746
TI  - Subdural empyema due to Enterococcus faecalis.
AB  - Central nervous system infections due to Enterococcus species are uncommon. We
      report the first case of subdural empyema due to Enterococcus faecalis. Following
      partial treatment of a middle ear infection due to Enterococcus species and mixed
      coliforms, the patient developed signs of meningeal involvement. A lumbar
      puncture showed a raised polymorph cell count, but was sterile on culture; broad
      spectrum antimicrobial therapy with cefotaxime, flucloxacillin and metronidazole
      was commenced. Following development of focal neurological signs, a CT scan
      revealed a subdural collection. Drainage and culture of the pus yielded a pure
      growth of Enterococcus faecalis. This case demonstrates the need to remain aware
      of the ability of the Enterococcus to cause serious infections and to direct
      specific antimicrobial therapy accordingly.

PMID- 9571747
TI  - High-level aminoglycoside-resistant enterococcus causing endocarditis
      successfully treated with a combination of ampicillin, imipenem and vancomycin.
AB  - We describe a case of bacterial endocarditis caused by Enterococcus faecalis,
      which was highly resistant to aminoglycosides. The patient was successfully
      treated with a combination of ampicillin, imipenem and vancomycin. We believe
      this to be the first case in the literature to be treated successfully with this
      combination.

PMID- 9571748
TI  - A case of Plesiomonas shigelloides cellulitis and bacteraemia from northern
      Europe.
AB  - Bacteremia caused by Plesiomonas shigelloides is a rare event, often associated
      with consumption of seafood and fresh or estuarine water in temperate or tropical
      climates. Most patients have showed underlying health disorders. Here we present
      a case of P. shigelloides septicaemia and cellulitis of the left hand associated
      with fish handling in Northern Sweden (65 degrees latitude north). The patient,
      who suffered from multiple myeloma, recovered uneventfully after initial
      treatment with intravenous cefuroxime followed by a course of oral ciprofloxacin.
      P. shigelloides seems to be ubiquitous in freshwater world-wide and may cause
      invasive infections also in cold climate areas.

PMID- 9571749
TI  - Murine typhus presenting with multiple white dots in the retina.
AB  - The retinal manifestations of murine typhus have rarely been reported. We report
      a case of murine typhus with multiple retinal white dots, which are similar to
      the presentation of multiple evanescent white dot syndrome.

PMID- 9571750
TI  - Scrub typhus associated with multiorgan failure: a case report.
AB  - The spectrum of clinical severity for scrub typhus ranges from inapparent, mild,
      to severe or fatal. The pathologic changes are focal or disseminated multiorgan
      vasculitis of the small blood vessels, a fact that helps explain the great
      diversity of clinical manifestations that can be encountered. We reported a case
      of scrub typhus with unusual and serious multiorgan involvement, including
      tubulointerstitial nephritis (TIN) with acute renal failure (ARF), interstitial
      pneumonitis with adult respiratory distress syndrome (ARDS), disseminated
      intravascular coagulation (DIC), liver function impairment, upper
      gastrointestinal bleeding, prolonged hyperamylasaemia and hyperlipasaemia.
      Chloramphenicol administration rapidly altered the clinical course, but with
      sequelae of renal impairment and prolonged hyperamylasaemia and hyperlipasaemia
      for 10 months.

PMID- 9571751
TI  - Candida glabrata prosthesis infection following pyelonephritis and septicaemia.
AB  - Candida glabrata is a well-known cause of lower urinary tract infections.
      Systemic infections caused by this organism are less common, but have increased
      dramatically in recent years. Prosthesis infection caused by C. glabrata is
      extremely rare. We report a case of prosthesis failure due to C. glabrata 5 y
      after candidaemia and pyelonephritis caused by this organism. The same C.
      glabrata strain was isolated from both infections, as confirmed by the random
      amplified polymorphic DNA (RAPD) method.

PMID- 9571752
TI  - Treatment of complicated pulmonary echinococcosis with albendazole in childhood.
AB  - The case of an 11-year-old boy suffering from pulmonary hydatid disease with
      rupture and bacterial superinfection is presented. After 3 courses of
      chemotherapy with albendazole the boy recovered fully, uneventfully and without
      relapse. Conservative management should always be considered before surgical
      intervention in children with echinococcosis, even when complications have
      occurred.

PMID- 9571753
TI  - Interleukin-6 in the fever and multiorgan crisis of pheochromocytoma.
AB  - A 31-y-old black man with neurofibromatosis, alcoholism and hypertension was
      admitted because of abdominal pain, hematemesis and cough. In the hospital he had
      prolonged fever and developed a multiorgan crisis. Despite thorough
      investigation, no infectious cause for fever was found. Urinary catecholamines
      and metabolites were markedly elevated. Computerized tomography revealed a mass
      abutting the left kidney. A diagnosis of pheochromocytoma was made, and as soon
      as treatment with phenoxybenzamine and propranolol was begun, the fever resolved.
      Serum interleukin-6 (IL-6) concentration was initially elevated, decreased after
      the start of adrenergic blockade, and gradually fell to an undetectable level
      after surgery. These observations suggest that interleukin-6 might have been
      causally related to the patient's fever and possibly the multiorgan crisis.

PMID- 9571754
TI  - Application of probability techniques to the objective interpretation of
      veterinary clinical biochemistry data.
AB  - Methods for the interpretation of veterinary clinical biochemistry have not
      developed as rapidly as biochemical technology. However, the results of clinical
      biochemistry tests are only of value when they are interpreted appropriately. A
      retrospective study was undertaken to investigate the equine biochemistry data
      which had been stored in a veterinary hospital database. By applying percentile
      analysis and Bayesian probability methods to the clinical biochemistry and
      corresponding diagnosis data, a novel method for the interpretation of clinical
      biochemistry data has been developed. The method allows clinicians to determine
      whether a biochemistry value is abnormal, its degree of abnormality, and the most
      likely associated diagnoses. The method could be used to investigate a practice
      based population and may have significant implications for the interpretation of
      clinical biochemistry data in veterinary medicine in the future.

PMID- 9571755
TI  - Risk estimates for dichotomous genetic disease traits based on a cohort study of
      relatedness in purebred dog populations.
AB  - As a result of strong selection in closed gene pools, dog breeds represent
      populations of highly related animals. Prominent founder-effects are responsible
      for inherited diseases occurring in particular breeds, and each breed may have
      several breed-related diseases, often with a high incidence. Such inherited
      diseases are a major problem in purebred dog populations, and probably threaten
      their survival. On the basis of pedigree information held by the National Kennel
      Clubs and reliable medical data of a representative longitudinal cohort,
      estimates have been made of the relative risks of dichotomous disease traits in
      all combined breeding stock. This approach is independent of assumptions about
      modes of inheritance or thresholds. In a cohort study, all the common ancestors
      of the cases are selected and their degree of relatedness to both cases and
      controls is estimated. The ancestors which are positively associated with the
      dichotomous disease trait are selected on the basis of scores of relatedness. To
      reduce the number of parameters, while maintaining maximal informativeness, a
      principal component analysis is applied. Finally a logistic model, based on the
      principal components and the case control definitions, describes the most likely
      pattern of the passage of genetic risk factors down the generations. Estimates of
      relatedness to seven highly related ancestors were sufficient to describe the
      distribution of disease in a population of Dutch labrador retrievers. This
      approach may be used for genetic counselling for any clinical phenotypically
      dichotomous trait in such a highly related population of companion animals, and
      may also help to identify suitable dogs for molecular studies of the underlying
      defect.

PMID- 9571756
TI  - Efficacy of an ivermectin controlled-release capsule against nematode and
      arthropod endoparasites in sheep.
AB  - Five controlled trials were conducted in Germany or in the United Kingdom, using
      74 female sheep of merino or Dorset horn breeds, to evaluate the efficacy of an
      ivermectin controlled-release capsule against naturally acquired or induced
      infections of gastrointestinal nematodes, lungworms and nasal bot larvae and
      against incoming infections with gastrointestinal and pulmonary nematodes. Half
      of the animals were treated with one ivermectin controlled-release capsule that
      delivered ivermectin at the rate of 1.6 mg per day for 100 days while the other
      half remained untreated. Parasites were counted 21, 28, 35 or 56 days after
      administration of the capsule. The treatment was highly effective (> or = 99 per
      cent) against established parasites of the following species: Haemonchus
      contortus (adults and fourth-stage larvae), Ostertagia circumcincta, O pinnata, O
      trifurcata, Ostertagia species fourth-stage larvae, Trichostrongylus axei, T
      colubriformis, T vitrinus, Cooperia curticei, Nematodirus battus, N filicollis,
      Strongyloides papillosus, Chabertia ovina, Oesophagostomum venulosum, Trichuris
      ovis, Tr skrjabini, Dictyocaulus filaria, Protostrongylus rufescens and Oestrus
      ovis (larvae). The treatment prevented the establishment of the gastrointestinal
      nematodes H contortus, O circumcincta, T axei, T colubriformis, C curticei, N
      battus, N filicollis, Ch ovina, Oe vennulosum and the establishment of the
      lungworm D filaria by > 99 per cent compared with untreated controls (P < or =
      0.01).

PMID- 9571757
TI  - Nasal rhinosporidiosis in dogs: four cases from Europe and a review of the
      literature.
AB  - This paper describes four cases of canine rhinosporidiosis which occurred in
      Italy in 1994 and 1995. Four dogs with a history of exposure to the muddy
      environment of rice fields, developed respiratory signs. Rhinoscopy revealed
      nasal polypoid lesions with a characteristic gross appearance due to the presence
      of multiple, tiny, white-yellowish spots representing sporangia filled with
      spores. In cytological samples obtained by brushing, many spores were present in
      an inflammatory background. Histologically, the polyps consisted of fibrovascular
      tissue embedding sporangia in different developmental stages, and free spores
      which elicited a severe pyogranulomatous inflammation. All the dogs were treated
      surgically and the condition did not recur in two cases during a year's follow-up
      and in the other two cases during two years.

PMID- 9571758
TI  - Ultrasonographic findings in three cows with peritonitis in the left flank
      region.

PMID- 9571759
TI  - Swayback warning.

PMID- 9571760
TI  - Cat castrations and veterinary nurses.

PMID- 9571761
TI  - Cat castrations and veterinary nurses.

PMID- 9571762
TI  - Cat castrations and veterinary nurses.

PMID- 9571763
TI  - Veterinary nursing degrees.

PMID- 9571764
TI  - Vaccination, health checks and the 24-hour service.

PMID- 9571766
TI  - Hox gene expression, AV-1 antigen expression, and cartilage pattern formation in
      chick recombinant limb buds.
AB  - A recombinant limb bud composed of dissociated and reaggregated mesenchyme and an
      ectodermal jacket develops a limblike structure with bifurcated and segmented
      cartilage. We compared the cartilage structure formed from recombinants that were
      composed of mesenchymal cells derived from the limb bud progress zone at various
      stages. In the case of recombinants containing distal mesenchyme of early-stage
      limb buds (stage 18 or 20), long and thick cartilage structures were formed in
      the proximal region, and segmented digitlike structures were formed in the distal
      region. On the contrary, in the case of recombinants containing distal mesenchyme
      of late-stage limb buds (stage 25 or 27), only poorly developed cartilage
      structures were formed. Next, we analyzed expression patterns of the position
      specific genes HoxA11, A13 and D12 and the position-specific antigen AV-1 protein
      in recombinants containing distal mesenchyme of stage 20 limb buds (stage 20
      recombinants) or stage 25 limb buds (stage 25 recombinants). In stage 20
      recombinants, HoxA11 was expressed throughout the mesenchyme, but HoxA13 was
      expressed only in the distal half of the mesenchyme. In stage 25 recombinants,
      HoxA13 was expressed throughout the mesenchyme, but HoxA11 was only faintly
      expressed. The expression pattern of HoxD12 was similar to that of HoxA13 in both
      stage 20 and stage 25 recombinants, and no asymmetric expression pattern, which
      is observed in normal limb buds, was detected. AV-1 antigen was expressed in the
      core region of stage 20 recombinants, and anteroposterior asymmetry, which is
      observed in the anterior-ventral-distal region of normal limb buds, was not
      found. No AV-1 expression was observed in stage 25 recombinants. These results
      suggest that the mesenchyme in recombinants shows spatially controlled
      gene/protein expressions along the proximodistal axis, and that these differences
      in gene/protein expressions may affect cartilage pattern formation in
      recombinants.

PMID- 9571767
TI  - Detection of growth factors and proto-oncogene mRNA in the growing tip of red
      deer (Cervus elaphus) antler using reverse-transcriptase polymerase chain
      reaction (RT-PCR).
AB  - Deer antler is a unique mammalian organ that has an annual cycle of regeneration.
      The antler grows very rapidly from the tip at up to 1 cm/day in red deer for a 90
      to 120-day period. It is hypothesised that locally produced growth factors are
      required to control and stimulate this growth. The tip of the growing antler from
      animals whose antlers had been growing for 30, 60, or 90 days was dissected into
      four zones: epidermis/dermis, reserve mesenchyme, precartilaginous, and
      cartilaginous. Total RNA was extracted, and the presence of various growth
      factors and proto-oncogenes was detected using RT-PCR, IGF-I, IGF-II, TGF beta 1,
      TGF beta 2, c-fos, c-myc, and beta-actin were all present as single bands of the
      expected molecular weight in the four zones of the antler at each stage of
      growth. There were higher levels of IGF-I, TGF beta 2, and c-myc relative to beta
      actin in the epidermis/dermis layer than in the other three zones. There were no
      differences in the expression of any of the genes between the three stages of
      growth. The presence of TGF beta 3 cannot be confirmed since multiple bands were
      seen in all antler tissues. A single band of the expected size for TGF alpha was
      seen only in the epidermal/dermal layer of the antler, with multiple bands of
      different molecular weight being detected in the other zones of the antler. This
      work has demonstrated the presence of multiple growth factors in the growing deer
      antler and supports the hypothesis that paracrine/autocrine stimulation is
      important for regulating antler growth.

PMID- 9571768
TI  - Metastasizing mammary carcinomas in H19 enhancers-Igf2 transgenic mice.
AB  - The insulin-like growth factor II is mitogenic for a number of cell types and can
      inhibit apoptosis. The frequent expression of this gene in human and experimental
      animal tumors indicates that insulin-like growth factor-2 may play an important
      role in tumor development. It has also been hypothesized that overexpression of
      this growth factor may be responsible for the increased incidence of childhood
      tumors in patients with Beckwith-Wiedemann syndrome. To assess the effects of
      Igf2 on tumor development we produced six transgenic mouse lines that express the
      gene under the control of the H19 enhancers. Transgenic expression was initiated
      in the embryonic period but remained high in several adult tissues, including the
      mammary gland, lung, and liver. Adult transgenic females from five of the
      transgenic lines developed often multiple mammary tumors that had the ability to
      metastasize. Increased incidence of other solid tumors was also noted in older
      mice. These findings indicate that Igf2 expression increases the probability of
      malignant transformation and that the mammary gland is at a particularly high
      risk of tumor development in response to chronic increase in Igf2 gene dosage.

PMID- 9571769
TI  - Temperature but not season affects the transplantation immunity of anuran
      amphibians.
AB  - The effects of ambient temperature (22 degrees C/10 degrees C) and season
      (summer/winter) on anuran skin allograft and xenograft rejection was tested in
      frogs (Rana temporaria and R. esculenta) and toads (Bufo bufo, Bombina variegata,
      and Bombina bombina). Mean graft survival times were significantly prolonged at
      the low temperature in a species-specific manner, the edible frog (R. esculenta)
      being the most sensitive and the common toad (Bufo bufo) relatively resistant.
      Allografts were more temperature-dependent than xenografts; in the latter case,
      temperature sensitivity was specific to each donor-host combination. Rejection of
      second-set grafts in R. esculenta was accelerated both in warmth and in cold, but
      second-set grafts were less temperature-sensitive than sensitizing ones. Both in
      summer and in winter, R. esculenta rejected allografts promptly at 22 degrees C
      but slowly at 10 degrees C. In both seasons, Bombina variegata kept at 22 degrees
      C rejected allografts in a chronic manner. This indicates that amphibian
      transplantation immunity depends on the donor-host genetic disparity and ambient
      temperature but is independent of season.

PMID- 9571770
TI  - Immunological detection and quantification of oxidized proteins by labelling with
      digoxigenin.
AB  - An immunological assay, based on the digoxigenin/anti-digoxigenin system, was
      developed to detect and quantify carbonyl moieties that result from oxidative
      damage to proteins. Bovine serum albumin (BSA) was oxidized by a hydroxyl radical
      generating system consisting of ascorbate/Fe(III)/O2. The resulting albumin
      derived carbonyls were labelled with digoxigenin-hydrazide and detected by dot
      blotting with an anti-digoxigenin antibody conjugated to alkaline phosphatase.
      Quantification was carried out by a densitometric analysis. This system allows
      the detection of a pmole-amount of carbonyl groups on blots. The assay covers a
      range of sensitivity from 1.26 to 126 pmoles. Another feature of this method is
      its application to a complex protein mixture (homogenate) to analyze the
      oxidative status of individual proteins, as are shown for intestinal brush border
      membrane homogenate of a rat.

PMID- 9571771
TI  - HPLC profile analysis of oleanene-glucuronides in several edible beans.
AB  - HPLC analysis and yield of oleanene-glucuronide (OG) was done on some
      commercially available edible beans: seeds of Glycine max, Glycine max cv.
      Kuromame, Phaseolus vulgaris cv. Torosuku, Phaseolus vulgaris cv. Toramame,
      Phaseolus vulgaris cv. Taishokintoki, Phaseolus coccineus cv. Ooshirobana,
      Phaseolus coccineus cv. Murasakihanamame, Vigna unguiculata cv. Chuguro, Vigna
      angularis cv. Dainagon, Arachis hypogaea, Pisum sativum, and Vicia faba. All the
      beans listed above have OG, though in varying the amounts. Furthermore the HPLC
      profiles of beans belonging to the same genus were very similar except for that
      of the Vigna genus. There was no great difference of the HPLC profiles with
      respect to the cultivated varieties. The structures of the major OGs in each type
      of beans were identified as soyasaponins I (1) and V (2), and phaseoside I (3)
      (Phaseolus vulgaris and P. coccineus); 1 and soyasaponin II (4) (Glycine max); 1
      and 2 (Vigna unguiculata); 1 (Pisum sativum, Arachis hypogaea and Vicia faba). In
      contrast, those in Dainagon (Vigna angularis cv. Dainagon) were identified as
      azukisaponins II (5) and VI (6).

PMID- 9571772
TI  - Polysaccharides from Agaricus blazei stimulate lymphocyte T-cell subsets in mice.
AB  - Subset analysis of splenic lymphocytes using flow cytometry showed that the
      percentages of Thy1.2-(pan T-cells), L3T4-(CD4, helper T-cells), and Lyt2-(CD8,
      cytotoxic T-cells) positive cell populations were significantly increased in mice
      orally administered a hot water-soluble fraction from Agaricus blazei as compared
      with mice treated only with saline. 13C-NMR data indicates that the main
      component in the active polysaccharide is the complex of alpha-1,6- and alpha-1,4
      glucan, which had already been shown to have anti-tumor activity against Sarcoma
      180. It seems that the polysaccharide from Agaricus blazei may be an effective
      prophylactic, protecting humans against cancer by stimulating lymphocytes such as
      cytotoxic T-cells.

PMID- 9571773
TI  - Novel bioactive oxazolomycin isomers produced by Streptomyces albus JA3453.
AB  - Two novel oxazolomycin isomers, oxazolomycins B (2) and C (3), were isolated from
      the fermentation broth of an oxazolomycin-producing strain, Streptomyces albus
      JA3453. Both compounds are geometrical isomers of oxazolomycin (1), the
      configurations of their triene moieties being (4'E, 6'E, 8'E) (2) and (4'Z, 6'E,
      8'E) (3) while that of oxazolomycin (1) is (4'Z, 6'Z, 8'E). Compounds 2 and 3
      exhibited potent inhibitory activity against crown gall formation with the same
      MIC (0.8 microgram/disk) as oxazolomycin. Compounds 2 and 3 showed no
      antibacterial activity against Agrobacterium tumefaciens, in contrast to
      oxazolomycin which has specific anti-A. tumefaciens activity.

PMID- 9571774
TI  - Catalase catalyzes of peroxynitrite-mediated phenolic nitration.
AB  - Catalase catalyzed the peroxynitrite-mediated nitration of 4-hydroxyphenylacetic
      acid. The curve for the pH dependence of nitration was similar to that for the
      reaction between peroxynitrite and phenol. Cyanide, azide, and 3-amino-1,2,4
      triazole inhibited the nitration in a dose-dependent way. When catalase was mixed
      with peroxynitrite, Compound I was detected as an intermediate. Because azide was
      an electron donor for the peroxidatic action of catalase, and because 3-amino
      1,2,4-triazole inhibited catalase activity by binding with Compound I,
      peroxynitrite-mediated phenolic nitration was probably accompanied by Compound I
      formation. Both catalase and superoxide dismutase protected Escherichia coli from
      peroxynitrite toxicity.

PMID- 9571775
TI  - A very-high-density lipoprotein with clotting ability from hemolymph of sand
      crayfish, Ibacus ciliatus.
AB  - A very-high-density lipoprotein (VHDL) with a density of 1.27-1.29 g/ml was the
      most abundant lipoprotein in the hemolymph of the sand crayfish Ibacus ciliatus.
      The VHDL isolated by a density gradient ultracentrifugation consisted of 94%
      protein and 6% lipid reflecting its high density, and phospholipid was a
      predominant lipid component. The VHDL had an apolipoprotein of molecular mass 195
      kDa and its N-terminal amino acid sequence was identified as follows:
      LQPGLEYQYRYNGRVAA. This sequence was similar to those of clotting proteins from
      the spiny lobster Panulirus interruptus and the freshwater crayfish Pacifastacus
      leniusculus. Transglutaminase and Ca2+ also induced the VHDL to clot. Considering
      large amounts of VHDL in the hemolymph of sand crayfish, the VHDL not only
      functions as lipid carrier but plays an important role in the defense process of
      crustacea.

PMID- 9571776
TI  - Effect of dibromochloropropane (DBCP) on the hormone receptors of the male rat
      reproductive system.
AB  - The effects of dibromochloropropane (DBCP), a pesticide, on the male rat
      reproductive system were examined at morphological and hormonal expression
      levels. Changes of Leydig cells and seminiferous tubules were examined in rats
      treated with one subcutaneous (s.c.) injection of DBCP at doses of 10, 50, 75 and
      100 mg/kg of body weight. The Leydig cells degenerated and decreased in number in
      those rats with an s.c. injection of DBCP at a dose of 50 mg/kg of body weight.
      However, these morphological changes were not significant in those rats that were
      treated with four separate s.c. injections of DBCP at 10 mg/kg of body weight.
      The expression of luteinizing hormone receptor mRNA, which is specifically
      expressed in Leydig cells, was decreased significantly in the DBCP-treated rats
      as compared with the normal-control rats. The expression of follicle-stimulating
      hormone receptor mRNA was decreased to a mild degree in DBCP-treated rats. At a
      dose of 75 mg/kg of body weight, seminiferous tubules as well as Leydig cells
      were severely damaged morphologically and at hormonal receptor expression levels.
      Multinucleated giant cells appeared at a dose of 75 mg/kg of body weight. All the
      rats died at a dose of 100 mg/kg of body weight. Our data indicate that DBCP had
      a cytotoxic effect on the male rat reproductive system in a dose-dependent
      manner.

PMID- 9571777
TI  - Cell age distribution of erythrocytes at the incidence of cerebral stroke in
      stroke-prone spontaneously hypertensive rats, and their glutathione peroxidase
      activity.
AB  - To study the mechanism of the fall of glutathione peroxidase (GSH-Px) activity in
      erythrocyte after cerebral strokes in stroke-prone spontaneously hypertensive
      rats (SHRSP), erythrocytes were fractionated into low density erythrocytes (LD-E)
      and high density erythrocytes (HD-E) by a density gradient centrifugal method
      using Percoll solution, and fluctuation of the distribution ratio and changes of
      GSH-Px activity in fractionated erythrocytes were investigated. The distribution
      ratio of LD-E and HD-E in erythrocytes of SHRSP was about 4:1 at 5 weeks of age
      (n = 6), and the distribution to HD-E increased along with aging. While the
      distribution ratio was changed, however, there was no change in the GSH-Px
      activity in both LD-E and HD-E of erythrocytes. In senile, 30-week-old SHRSP (n =
      4) with advanced hypertension, the GSH-Px activity in the HD-E was lower, in
      proportion to the increase of the distribution rate against HD-E. On the other
      hand, in SHRSP (n = 5) having cerebral stroke, the distribution ratio of LD-E and
      HD-E was about 1:4. The GSH-Px activity was 31.4 +/- 2.9 units/10(10)
      erythrocytes in LD-E, which was hardly different from the value of SHRSP without
      stroke (35.7 +/- 3.3 units/10(10) erythrocytes). In HD-E, however, the activity
      was 18.2 +/- 2.2 units/10(10) erythrocytes, being lower than the activity of
      SHRSP without stroke. At the moment when the GSH-Px activity had dropped to 17
      units/mg hemoglobin, and the control diet was changed to one based on fish or a
      hydralazine treatment given, the activity recovered, and an increase in body
      weight and the distribution rate of the LD-E over HD-E was increased. It is clear
      from these experiments that the fall of erythrocyte GSH-Px activity observed
      after cerebral stroke is due to a decrease of LD-E and increase of HD-E, which
      has lowered activity. However, nothing definite is known on the relationship
      between the fall of GSH-Px activity in erythrocytes and disorder in cerebral
      tissue. It appears that the fall of the GSH-Px activity causes at least
      functional and structural changes in erythrocytes, which interfere with the
      delivery of oxygen to peripheral tissues, triggering oxidation stress in cerebral
      tissues.

PMID- 9571778
TI  - Effects of synthetic hydroxy isothiocyanates on microbial systems.
AB  - Hydroxy isothiocyanates (ITCs), including some new derivatives of naturally
      occurring compounds, were synthesized and their minimum inhibitory, minimum
      fungicidal, and minimum bactericidal concentrations for Aspergillus niger,
      Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli were
      estimated. These compounds were strongly antimicrobial; for example, 2-(4
      hydroxyphenyl) ethyl ITC inhibited growth of all strains examined at
      concentrations of 7.8 to 15.6 micrograms/ml. The ATP concentration in E. coli was
      markedly reduced when cells were treated with 2-(4-hydroxyphenyl)ethyl ITC.
      Inhibition of the growth of E. coli by 2-(4-hydroxyphenyl)ethyl ITC was decreased
      in the presence of cysteine. Streptolysin S production in washed cells of
      Streptococcus equisimilis was extremely sensitive to this ITC derivative and this
      inhibition also was counteracted by cysteine. The results showed that the ITC
      compounds had antimicrobial effects by blocking sulfhydryl groups.

PMID- 9571779
TI  - Purification and characterization of a novel cysteine synthase isozyme from
      spinach hydrated seeds.
AB  - A novel type of cysteine synthase (CSase, EC 4.2.99.8) isozyme, designated as
      CSase 1', was purified to homogeneity from hydrated spinach seeds. The enzyme had
      a molecular weight of 68,000 and consisted of two identical subunits of M(r),
      34,000. The apparent K(m) for O-acetyl-L-serine was 8.33 mM and that for sulfide
      was 0.66 mM. The activity of CSase 1' was maintained when it was treated at 60
      degrees C for 1 min. This novel enzyme was similar to CSases 1, 2, and 3 already
      purified from spinach leaves, in results of double immunodiffusion, molecular
      weight, subunit composition, K(m) values for O-acetyl-L-serine and sulfide, and
      heat stability. On the other hand, N-terminal amino acid sequence, effects of
      immunotitration, pH optimum, and effects of hydroxylamine on purified CSase 1'
      were different from those of the other CSases. Furthermore, it was found that
      CSases 2S and 3S isolated from hydrated spinach seeds were identical with the
      CSases 2 and 3 reported previously. It was also disclosed that CSases 1, 2, and 3
      were localized in chloroplasts, cytosol, and mitochondria, respectively.

PMID- 9571780
TI  - Association between hepatic triacylglycerol accumulation induced by administering
      orotic acid and enhanced phosphatidate phosphohydrolase activity in rats.
AB  - Orotic acid is known to cause fatty liver, but it is unclear whether this is
      caused partly by stimulation of the enzymes for triacylglycerol (TG) synthesis.
      To understand the change of hepatic TG metabolism in fatty liver induced by
      orotic acid, we determined the liver tissue TG level and phosphatidate
      phosphohydrolase (PAP) activity over time in rats fed on a diet containing orotic
      acid (OA). A dietary lipid content of 10% was achieved by using n-6 fatty acid
      rich corn oil in experiment 1, and n-6 fatty acid-rich safflower oil (SO) and n-3
      fatty acid-rich fish oil (FO) with the same polyunsaturated fatty
      acid/monounsaturated fatty acid/saturated fatty acid (P/M/S) ratio in experiment
      2. In experiment 1, an increase in the hepatic TG level due to OA intake was
      observed from day 5 onwards, the level rising approximately 6-fold by day 10. The
      activity of hepatic microsomal PAP, the rate-limiting enzyme in TG synthesis,
      increased markedly from day 5 onwards, concurrent with the liver diacylglycerol
      concentration. A strong correlation (r = 0.974) was observed between the hepatic
      TG level and microsome-bound PAP activity. In experiment 2, we investigated the
      effects of dietary fatty acid on OA-induced fatty liver. Compared with the n-6
      fatty acid-rich vegetable oil diet, the relative increase in hepatic TG was
      smaller with the n-3 fatty acid-rich FO diet, and hepatic PAP activity fell
      markedly to the level for an OA-free diet. In addition, the hepatic TG
      accumulation and serum TG concentration were lower in the FO group than in the SO
      group. Nevertheless, because the hepatic TG level was low, it seems that the
      inhibition of liver PAP activity by FO possibly had a strong influence on the
      accumulation of TG in the liver. In conclusion, enhanced TG synthesis mediated by
      changes in liver PAP activity was involved in the hepatic TG accumulation induced
      by OA administration, this change being markedly suppressed by dietary n-3 fatty
      acids.

PMID- 9571782
TI  - Isolation and identification of acetyl-CoA carboxylase inhibitors from green tea
      (Camellia sinensis).
AB  - An aqueous methanol extract from green tea showed potent acetyl-CoA carboxylase
      inhibitory activity. An active compound was isolated from the extract and
      identified as (-)-epigallocatechin gallate by instrumental analyses. The IC50
      value of (-)-epigallocatechin gallate was 3.1 x 10(-4) M. Among tea catechins and
      related compounds, nearly equal activity was found in (-)-epigallocatechin
      gallate and (-)-epicatechin gallate, whereas (+)-catechin, (-)-epicatechin, (-)
      epigallocatechin, gallic acid and methyl gallate each had no inhibitory activity.
      These results indicate that the 3-O-gallate group of the catechin structure was
      necessary for this activity. (-)-Epigallocatechin gallate inhibited triglyceride
      accumulation in 3T3-L1 cells at a concentration of 1.0 x 10(-7) M or higher.

PMID- 9571781
TI  - Cloning, sequence analysis, and expression in Escherichia coli of a gene coding
      for an enzyme from Bacillus circulans K-1 that degrades guar gum.
AB  - A 2,048-bp nucleotide sequence containing a gene coding for an enzyme that
      degraded guar gum from Bacillus circulans K-1 was identified by polymerase chain
      reaction walking. This G-gene consisted of 1,551 nucleotides coding for a protein
      with Mr 55,242. The enzyme was overexpressed in Escherichia coli JM109 cells by
      the cloning the G-gene downstream of the lac Z promoter of pUC19. The molecular
      mass of recombinant G-enzyme estimated by SDS-PAGE was 62 KDa, close to that from
      strain K-1. Analysis of the recombinant enzyme showed GalNAc, Xyl, GlcNAc, Man,
      Glc, and Gal to account for 1.7%, 14.4%, 6.1%, 3.2%, 54.2%, and 10.4%,
      respectively, of the total monosaccharides. Polyacrylamide gel electrophoresis of
      this enzyme with staining gave a red band. The results suggested that the sugars
      accounted for the differences in the molecular masses. The recombinant enzyme had
      two kinds of N-terminal sequences, Thr-Met-Ile-Thr-Pro-Ser-Phe-Ala-Ser-Gly-Phe
      Tyr-Val-Ile and Ile-Thr-Pro-Ser-Phe-Ala-Ser-Gly-Phe-Tyr-Val-Ile-Gly-Thr.
      Comparison of these sequences with the deduced N-terminal sequence coded for the
      G-gene showed that the amino acid, first Met, of the lac Z gene or the next
      residues Thr-Met in the recombinant enzyme were absent in the native enzyme.
      Methionines near and at the N-terminus of the mature protein probably were
      digested by methionine aminopeptidases of E. coli after translation. The
      properties of recombinant G-enzyme were similar to those of the enzyme from K-1
      cells.

PMID- 9571783
TI  - Role of N-acetylglutamate turnover in urea synthesis by rats treated with the
      thyroid hormone.
AB  - We determined whether the synthesis and degradation of N-acetylglutamate would
      regulate urea synthesis when the thyroid status was manipulated. Experiments were
      done on three groups of rats, each being given 6-propyl-2-thiouracil (PTU, a
      thyroid inhibitor) without a triiodothyronine (T3) treatment, treated with PTU +
      T3, or receiving neither PTU nor T3 (control). The plasma concentration and
      urinary excretion of urea, the liver concentration of N-acetylglutamate, and the
      liver N-acetylglutamate synthesis in rats given PTU alone were each significantly
      higher than in the control rats. Compared with the control rats, the liver N
      acetylglutamate degradation was significantly lower in those rats given PTU
      without the T3 treatment. Treatment of the PTU-treated rats with T3 reversed the
      effects of PTU to the values of the control rats. N-Acetylglutamate synthesis in
      the liver was closely correlated with the excretion of urea, and inverse
      correlation between the liver N-acetylglutamate degradation and urea excretion
      was found. These results suggest that the greater synthesis and lower degradation
      of N-acetylglutamate in the hypothyroid (PTU alone) rats would be likely to
      increase the hepatic concentration of this compound and stimulate urea synthesis.

PMID- 9571784
TI  - Suppression of the lethal effect of acidic-phospholipid deficiency in Escherichia
      coli by Bacillus subtilis chromosomal locus ypoP.
AB  - An acidic-phospholipid deficiency caused by the pgsA3 allele that encodes a
      defective phosphatidylglycerophosphate synthase in Escherichia coli is lethal.
      The only known mutations that suppress this lethality fully have been related to
      the major outer-membrane lipoprotein. We isolated a Bacillus subtilis chromosomal
      locus that suppresses the lethality when harbored in a low copy-number plasmid,
      without restoring the synthase activity or phospholipid composition to normal.
      The locus was first recognized to suppress the conditional lethality of E. coli
      YA5512 (pgsA3) that harbored an unidentified mutation(s), allowing its growth in
      LB medium but not in media of lower osmolarities. The locus was then found to
      suppress the lethality of pgsA3 in wild-type E. coli W3110. This locus, named
      ypoP in the database, had 37% nucleotide identity with the E. coli mprA gene, but
      the amplification of mprA had no suppressive effect. Plasmid pPOP1 containing
      ypoP completely prevented the decrease in the amount of a porin protein, OmpF, in
      the outer membrane and also cell mucoidy caused by pgsA3. The mechanisms
      underlying these unusual effects are discussed in relation to a putative stress
      signal(s) generated by the acidic-phospholipid deficiency.

PMID- 9571785
TI  - Alpha 2-adrenoceptor-mediated antisecretory effect of hypoxia in conscious rats.
AB  - Gastric acid secretion is suppressed, resulting in a significant rise in gastric
      pH, when conscious rats are exposed to hypoxia (Yamaji et al., 1996). When
      adrenal medullectomized rats were exposed to moderate (10.5% O2) hypoxia for 3 h,
      gastric acid secretion was restored to nearly the level in normoxia by the
      adrenal medullectomy. In severe (7.6% O2) hypoxia, the operation also caused an
      increase in the level of gastric acid output, although the extent was lower than
      that under 10.5% O2 hypoxic conditions. Gastric pH was normalized by the
      operation even with 7.6% O2 hypoxia. Similar results were obtained when
      reserpine, which causes an adrenergic discharge, was administered. When an alpha
      2-adrenoceptor blocking agent, yohimbine, was administered, the inhibitory effect
      of 10.5% and 7.6% O2 hypoxia on gastric acid secretion was almost completely
      removed. However, neither prazosin (an alpha 1-adrenoceptor blocker) nor
      propranolol (a beta-adrenoceptor blocker) showed any significant effects on
      gastric acid output in hypoxia. These results indicate that acute hypoxia
      stimulated the adrenergic response from the adrenal medulla, and that gastric
      acid secretion was consequently suppressed through alpha 2-adrenoceptor.

PMID- 9571786
TI  - Characterization of cDNAs encoding small and large subunits of ADP-glucose
      pyrophosphorylases from watermelon (Citrullus vulgaris S.).
AB  - Three cDNA clones encoding ADP-glucose pyrophosphorylases were isolated from a
      full red fruit cDNA library of watermelon (Citrullus vulgaris S.). Sequence
      analyses indicated that one clone, wms1, corresponds to the small subunit, and
      two clones, wml1 and wml2 (a partial gene), are the large subunits of AGPase. The
      presumed AGPase proteins encoded by wms1, wml1, and wml2 have 526, 526, and 481
      amino acids, respectively. The protein sequences have the conserved amino acids
      important for the substrate or regulator binding site, with some variation.
      Developmental changes in the amounts of wms1, wml1, and wml2 transcripts in
      fruits were measured by northern blot analysis. Their expression levels decreased
      from the small green to medium green stages, then increased in accordance with
      fruit ripening, which was different from those of tomato and oriental melon.

PMID- 9571787
TI  - cDNA cloning, expression, and mutagenesis of scytalone dehydratase needed for
      pathogenicity of the rice blast fungus, Pyricularia oryzae.
AB  - We purified scytalone dehydratase from the rice blast fungus, Pyricularia oryzae,
      and cloned its cDNA on the basis of its amino acid sequence. The deduced amino
      acid sequence was 62% identical to the scytalone dehydratase from Colletotrichum
      lagenarium. The expression of this gene was induced transcriptionally in the
      stationary phase when melanin synthesis occurs. We constructed a heterologous
      expression system for the enzyme in Escherichia coli, did deletion analysis with
      this system, and found that a C-terminal region is essential for the enzyme
      function.

PMID- 9571788
TI  - Biological activities of (1-->3)-beta-D-glucans with reducing glucose side
      chains.
AB  - Newly synthesized (1-->3)-beta-D-glucans with reducing glucose side chains (6-O
      glucopyranosylated curdlan and 3-O-glucopyranosylated curdlan, with glucose
      linked directly (except for anomeric carbon) had antitumor activity against mice
      sarcoma 180 in mice. The two glucans potentiated the reticuloendotheliai system
      and activated macrophages (increased their glucose consumption). The activity
      inducing tumor regressing factor of the glucan derivatives was stronger than a
      linear (1-->3)-beta-D-glucan (curdlan).

PMID- 9571789
TI  - Sequence of a cDNA encoding mouse ribosomal protein S14.
AB  - An involution-induced clone was identified by differential screening from a cDNA
      library of mouse mammary gland. The clone was identified as full-length cDNA
      encoding the 40S subunit of ribosomal protein S14 (rps14). Comparison of the
      deduced amino acid sequence to sequences of rps14 from humans, hamsters, and rats
      showed a conservation.

PMID- 9571790
TI  - Inhibition of HIV-1 protease by water-soluble lignin-like substance from an
      edible mushroom, Fuscoporia obliqua.
AB  - Activity that inhibited protease of human immunodeficiency virus type 1 was found
      in boiling water extracts of an edible mushroom, Fuscoporia obliqua. The active
      component was identified as a water-soluble lignin derivative of high molecular
      weight. Other polyphenols of low molecular weight and monomeric components of
      lignin did not inhibit the protease.

PMID- 9571791
TI  - Increasing effect of dietary taurine on the serum HDL-cholesterol concentration
      in rats.
AB  - Taurine, 2-amino ethanesulfonic acid, is the major free intracellular amino acid
      present in many tissues and plays an important role in lipid metabolism such as
      that of bile acid conjugation for fat absorption. The effect of taurine on the
      serum cholesterol level in normal rats was investigated. Taurine enhanced the
      serum HDL-cholesterol concentration in a dose-dependent manner without any change
      in total cholesterol.

PMID- 9571792
TI  - Increased conversion ratio of tryptophan to niacin in severe food restriction.
AB  - The effect of food restriction on the conversion ratio of tryptophan to niacin
      was investigated, because it is known that the conversion ratio is influenced by
      nutritional factors. A 20% casein diet was fed to rats ad libitum (control), 1/2
      the food of the control. 1/4 the food of the control, or starved for 9 days, and
      urine samples were collected to measure the urinary excretion of such tryptophan
      metabolites as kynurenic acid, xanthurenic acid, and nicotinamide. The conversion
      ratio in the 1/2, 1/4, or starving group increased at day 1 of the experiment,
      but returned to the original value from day 2. Only in the starving group did the
      conversion ratio extremely increase from day 6 to day 9, being about 5-times
      higher than that of the original value on day 9. The possible mechanism by which
      the conversion ratio increased during food restriction is discussed.

PMID- 9571793
TI  - Isolation and characterization of chitinase isoforms from the bulbs of four
      species of the genus Tulipa.
AB  - Six chitinase isoforms, designated TBC-1 to TBC-6, were purified to homogenity
      from the bulbs of four species (Tulipa bakeri, T. tarda, T. turkestanica, and T.
      praestans) of the genus Tulipa by CM-cellulose column chromatography, Butyl
      Toyopearl 650M hydrophobic column chromatography, gel filtration on Sephadex G
      75, and Mono-S fast protein liquid chromatography (FPLC). The chitinases had
      molecular weights of 30,000 and isoelectric points of 5.2 to 6.1. These
      chitinases were found to proteins with similar amino acid compositions and N
      terminal sequences. The tulip chitinases all had two half-cystine residues, one
      more than gladiolus bulb class IIIb chitinase, but many fewer than chitinases of
      plant class I (15-17 Cys residues/mol), II (5-8 Cys residues/mol), or III (6 Cys
      residues/mol). The N-terminal sequences of tulip chitinases were similar to the
      sequence of the gladiolus chitinase, but did not resemble sequence of any class
      of plant chitinase. The optimal pH of these chitinases toward glycolchitin was pH
      5. TBC-1 hydrolyzed (GlcNAc)6 into (GlcNAc)2, (GlcNAc)3, and (GlcNAc)4, and
      hydrolyzed (GlcNAc)5 into (GlcNAc)2 and (GlcNAc)3.

PMID- 9571794
TI  - A convenient and efficient synthesis of sialyl Lewis X.
AB  - A convenient synthesis of the sialyl Lewis X (sLe(x)) tetrasaccharide, NeuAc
      alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc (8), as a carbohydrate ligand for
      selectins is described. The key step is the reaction between NeuAc alpha 2
      3GalSMe (5) as a glycosyl donor and the suitably protected Fuc alpha 1-3GlcNAc
      derivative (4) as the glycosyl acceptor by using dimethyl(methylthio)sulfonium
      triflate (DMTST) as the promoter.

PMID- 9571795
TI  - Sweetness of lysozymes.
AB  - While examining the taste of various proteins, we found that hen egg-white
      lysozyme, a bacteriolytic enzyme, had sweetness. Lysozymes from other sources
      such as turkey and soft-shelled turtle also showed sweetness with different
      tastes, heavy or light. In contrast, human lysozyme was tasteless. The amino acid
      sequences of the various lysozymes were similar to that of hen lysozyme, but hen
      lysozyme did not show significant homology to sweet proteins.

PMID- 9571796
TI  - Green tea suppresses D-galactosamine-induced liver injury in rats.
AB  - Dietary supplementation with powder of a green tea extract suppressed the
      enhancement of plasma alanine aminotransferase and aspartate aminotransferase
      activities induced by D-galactosamine, but not by carbon tetrachloride, in a dose
      dependent manner in rats. The minimum dose to cause a significant effect was 1 to
      2%. Drinking green tea also suppressed plasma enzyme activities. These results
      indicate that green tea had a liver injury-preventive effect.

PMID- 9571797
TI  - The bovine IFN-omega 1 is biologically active and secreted at high levels in the
      yeast Pichia pastoris.
AB  - The gene coding for bIFN-omega 1 was isolated from bovine genomic DNA by
      polymerase chain reaction (PCR). Recombinant bIFN-omega 1 was expressed in the
      yeast Pichia pastoris and high levels of the recombinant protein (0.4 mg ml-1)
      were secreted to the culture media. The obtained bIFN-omega 1 showed a cross
      species antiviral activity on four mammalian cell lines of calf, pig, hamster and
      human origin, but this activity was absent on Madin-Darby canine kidney (MDCK)
      cells. A delivery carrier was developed to permit a better release of bIFN-omega
      1. When compared with a control group, an increase in 6 days in the corpus luteum
      lifespan was obtained in cyclic ewes following three interferon (IFN)
      intrauterine administrations on days 9, 10 and 11 post-estrus. In summary, these
      results demonstrated for the first time that biologically active recombinant bIFN
      omega 1 was highly secreted by P. pastoris showing antiviral activity in
      different cell lines and an antiluteolytic effect in cyclic ewes, with no
      detrimental effects on the animals.

PMID- 9571798
TI  - Development of ELISA and enzyme-linked immunofiltration assay (ELIFA) methods for
      monitoring cyclodextrin glycosyltransferase (CGTase) production and bacterial
      growth in Bacillus macerans batch cultures.
AB  - Immunochemical methods were developed for monitoring cyclodextrin (CD)
      glycosyltransferase (CGTase) production and growth of an industrial CD-producing
      Bacillus macerans strain. Extracellular concentrations of CGTase released into a
      non-transparent culture medium during a 44 h long fermentation were detected by
      an indirect antigen inhibition enzyme-linked immunosorbent assay (ELISA). The
      ELISA was sensitive (minimal detection level 6 ng ml-1) and highly reproducible
      (coefficients of variation < or = 1.2 and 5.9%, within-runs and between-runs,
      respectively) compared to assays of CGTase activity (coefficients of variation <
      or = 4.2 and 7.0%, respectively). The ELISA, in combination with enzyme activity
      measurements, was useful to detect the decrease in the specific CGTase activities
      after 36 h of incubation, which was clearly indicative of the proteolytic
      degradation of CGTase. B. macerans cell numbers were estimated using an enzyme
      linked immunofilter assay (ELIFA). The assay took less than 1 h and the
      coefficients of variation within and between-runs (2.9-6.4%) were considerably
      less than for viable counting (10.6-15.4%). In the exponential phase of growth,
      ELIFA results correlated more closely with the cell counting based on total
      protein than with viable counts. Nevertheless, in the phase of cell lysis, the
      bacterial cell number was systematically underestimated by ELIFA in comparison to
      both viable cell number and total protein determinations. Thus cell antigens
      detected with immunological procedures might be lost during the transition from
      vegetative cells to spores. On the other hand, the ELIFA procedure was specific
      for B. macerans cells and was a better indicator of the onset of the different
      growth phases than the cell numbers calculated from the protein assay.

PMID- 9571799
TI  - Enzymatic specificity and hydrolysis pattern of the catalytic domain of the
      xylanase Xynl from Rhodothermus marinus.
AB  - The catalytic domain of a xylanase from Rhodothermus marinus was produced in
      Escherichia coli. The catalytic domain belongs to glycosyl hydrolase family 10.
      The produced protein has a 22-amino acid leader peptide followed by a 411-amino
      acid truncated xylanase. The molecular mass was 48 kDa and the recombinant
      xylanase had a pI of 4.9. The pH and temperature optima for activity were
      determined to be 7.5 and 80 degrees C, respectively. At that temperature the
      enzyme had a half-life of 1 h 40 min. An addition of 1 mM calcium stabilized the
      activity of the enzyme at 80 degrees C. The xylanase had its highest specific
      activity on oat spelt xylan but was active also on other xylans and to a limited
      extent on some other polysaccharides (soluble glucans). No exo- or endo-cellulase
      activity was observed. Hydrolysis of xylo-oligomers and oat spelt xylan was
      studied and the predominant products of hydrolysis were xylobiose and xylotriose.
      The enzyme was inactive on xylobiose, xylotriose and on the soluble fraction from
      oat spelt xylan. The R. marinus xylanase is shown to have a strong preference for
      internal linkages and is therefore classified as an endo-xylanase.

PMID- 9571800
TI  - Stability of alpha-amylase immobilized on poly(methyl methacrylate-acrylic acid)
      microspheres.
AB  - Poly(methyl methacrylate-acrylic acid) microspheres were prepared and the acid
      groups were activated by using either carbodiimide (CDI) or thionyl chloride
      (SOCl2). alpha-Amylase was covalently bound on these activated microspheres. The
      properties of the immobilized enzyme were investigated and compared with those of
      the free enzyme. The relative activities were found to be 80.4 and 67.5% for
      carbodiimide and thionyl chloride bound enzymes, respectively. Maximum activities
      were obtained at lower pHs and higher temperatures upon immobilization compared
      to free enzyme. No change in Vmax and approximately 12-fold increase in K(m) were
      observed for immobilized enzymes. The enzyme activities, after storage for 1
      month, were found to be 24.5 and 52.5% of the initial activity values for CDI and
      SOCl2 activated matrices, respectively. On the other hand the free enzyme lost
      its activity completely in 20 days. Immobilization, storage stability and
      repeated use capability experiments carried out in the presence of Ca2+ ions
      demonstrated higher stability, such as SOCl2 immobilized enzyme retained 83.7%
      and CDI immobilized enzyme retained 90.3% of the original activity of the enzyme.
      The immobilized enzymes that were used 20 times in 3 days in repeated batch
      experiments demonstrated that, in the absence of Ca2+ ions about 75% and in the
      presence of Ca2+ ions greater than 90% of the original enzyme activity was
      retained.

PMID- 9571801
TI  - Recombinant gene expression in Escherichia coli cultivation using lactose as
      inducer.
AB  - The use of lactose as inducer of foreign gene expression under control of the lac
      UV5 promoter was investigated in recombinant Escherichia coli. Chicken muscle
      troponin C (TnC) gene was transcripted by T7 RNA polymerase and expressed in
      bioreactor cultivations after a feed-forward controlled fed-batch growth phase.
      Cell concentrations of 22 g l-1 dry cell weight (DCW)--before induction started-
      were used to achieve a TnC content of 19.5% of total cell protein through an
      induction strategy that combined the addition of a specific lactose amount of 4.7
      g g-1 DCW divided into three pulses and the addition of yeast extract (1 g l-1)
      together with the second and the third lactose pulses. The results presented
      suggest that the residual lactose concentration plays an important role on the
      production of the heterologous protein.

PMID- 9571802
TI  - Estimation of biomass and specific growth rate in a recombinant Escherichia coli
      batch cultivation process using a chemical multisensor array.
AB  - A chemical multisensor array is used in combination with an artificial neural
      network to estimate the biomass concentration and specific growth rate in a
      recombination Escherichia coli batch cultivation. It is shown that by providing
      sufficient information to the artificial neural network, an accuracy comparable
      to that of an established dry weight method can be achieved. The obtained
      prediction error (1 sigma) of 0.043 g l-1 for biomass compares well with the
      error of the dry weight method in this low biomass concentration range (0.1-3 g l
      1). The prediction for the specific growth rate is accurate during important
      parts of the cell growth (1 sigma = 0.025 h-1). The results show that this non
      invasive method is potentially useful for estimating biomass and specific growth
      rate on-line in bioprocesses.

PMID- 9571803
TI  - The relationship between intracellular UDP-N-acetyl hexosamine nucleotide pool
      and monoclonal antibody production in a mouse hybridoma.
AB  - The effect of intracellular UDP-N-acetyl hexosamine accumulation in a murine
      hybridoma was investigated using tunicamycin and ammonium chloride. The treatment
      of cells with tunicamycin resulted in the inhibition of glycosylation of the
      secreted monoclonal antibody (IgGl) and cell growth arrest. Tunicamycin
      concentrations of 0.01-0.1 microgram ml-1 resulted in the formation of both
      glycosylated and non-glycosylated heavy chains of the immunoglobulin, whereas
      complete inhibition of protein glycosylation was observed at higher
      concentrations of tunicamycin. Tunicamycin treatment also resulted in a dose
      dependent accumulation of UDP-N-acetyl hexosamine. It was concluded that the
      specific monoclonal antibody production rate (qMab) was not dependent on the
      extent of glycosylation. Treatment of cells with NH4Cl also resulted in dose
      dependent accumulation of UDP-N-acetyl hexosamine. Supplementation of cultures
      with 10 mM NH4Cl resulted in a 40% reduction in cell growth rate and a 36%
      increase in the qMab. The data suggest that the reduction in growth rate and not
      UDP-N-acetyl hexosamine accumulation was the cause of increased qMab in the
      ammonium supplemented cultures. Ammonium chloride did not affect the extent of
      protein glycosylation. We conclude that UDP-N-acetyl hexosamine does not act as a
      mediator of enhanced rates of monoclonal antibody synthesis in the hybridoma cell
      culture system.

PMID- 9571804
TI  - Single turnover mechanism of a trypsin-reactor with high enzyme concentration.
AB  - A small column containing 2 mM CH-Sepharose 4B-immobilized trypsin was connected
      to a flow injection device equipped for potentiometric measurements (0.01-2 mM
      protons) and for post-column analysis by spectrophotometry and capillary
      electrophoresis (CE). The device was engaged with N alpha-benzoyl-L-arginine pNO2
      anilide (BAPNA), beta-lactoglobulin (beta-Lac) and peptides of V8-protease
      predigested beta-Lac. At a given flow rate, the reaction with BAPNA or beta-Lac
      (below 2 mM) produced about 1 proton per substrate molecule in each sample
      (linear relation to substrate amount); with peptides (below 22 mM), the reaction
      did not exceed 0.17 acid equivalents per substrate molecule (hyperbolic
      dependence). Final experiments demonstrated that the reactor gave a correct
      estimate of available lysine in peptides of beta-Lac modified with 5
      nitrosalicylaldehyde. The data could be predicted by a kinetic model describing
      the reactor performance in 'single turnover' conditions. The interplay between
      resident time and the non-catalytic amount of trypsin prevented each enzyme
      molecule from recycling as well as each substrate molecule (containing one or
      more cleavage sites) from encountering the enzyme more than once. In conclusion,
      both from the experimental and the theoretical point of view, this work permitted
      the analysis of trypsin behaviour in some extreme working conditions and
      indicates how to modulate the performance of an endoprotease-based reactor. A
      brief discussion on potential applications in protein mapping and tagging and in
      the quantitative analysis of protein bioavailability by means of a biosensorial
      strategy is also described.

PMID- 9571805
TI  - Enantioselectivity of a recombinant esterase from Pseudomonas fluorescens towards
      alcohols and carboxylic acids.
AB  - A recombinant esterase from Pseudomonas fluorescens (PFE) was produced from E.
      coli cultures and the enantioselectivity towards a series of racemic substrates
      was investigated. PFE exhibited high rate and enantioselectivity in the acylation
      of alpha-phenyl ethanol with vinyl acetate in toluene (E > 100) and the
      hydrolysis of the corresponding acetate in phosphate buffer (E = 58). In sharp
      contrast, extremely low enantioselectivity (E from 1.1 to 7) was found for the
      acylation of a series of 1,2-O-protected glycerol derivatives and the hydrolysis
      of 3-phenylbutyric acid methylester. Almost no reaction occurred with alpha
      phenyl propanol and its acetate and 2-phenylbutyric acid ethylester.

PMID- 9571806
TI  - Direct sequencing of bacterial artificial chromosomes (BACs) and prokaryotic
      genomes by biotin-capture PCR.
AB  - Determination of unknown DNA sequences adjacent to known segments is an important
      task in genome-related research. We have applied the methodology of biotin
      capture PCR for direct sequencing of bacterial artificial chromosomes (BACs) and
      bacterial genomes. The strategy involves extension of a biotinylated primer from
      a known locus into unknown regions of the template to yield single-stranded DNA,
      which is immobilised onto paramagnetic beads. An arbitrary primer initiates
      extension from the unknown region and back towards the known locus. The arbitrary
      primer contains a universal primer 'handle', which is utilised for subsequent
      amplification. The PCR products are then directly sequenced by solid-phase or
      cycle sequencing. The fact that BACs or bacterial chromosomes can be sequenced
      without prior purification or subcloning might be useful in numerous
      applications, such as gap-filling, sequencing of regulatory regions upstream
      known genes and determination of intron/exon-boundaries.

PMID- 9571807
TI  - [Diagnosis and treatment of patients with hypertension].

PMID- 9571808
TI  - [Evaluation of medical technology in Europe].

PMID- 9571810
TI  - [Is low birth weight a risk factor for development of non-insulin-dependent
      diabetes mellitus?].
AB  - Different lines of evidence indicate that low birth weight and insufficient
      intrauterine nutrition may represent significant risk factors for the development
      of late onset non-insulin dependent diabetes mellitus (NIDDM). The evidence
      includes epidemiological studies, animal studies and metabolic studies of non
      diabetic subjects with low birth weight. Insufficient intrauterine nutrition may
      induce a variety of abnormalities of metabolism in different tissues including
      muscle, liver, pancreas and adipose tissue; which can all in turn be related to
      known defects of glucose metabolism involved in the development of hyperglycaemia
      in NIDDM. Future studies should address the important question as to which roles
      genetics versus intrauterine and postnatal factors play in the etiology of late
      onset NIDDM in the general population. This may have important implications for
      which initiatives that should be applied to prevent NIDDM.

PMID- 9571809
TI  - [Glucagon-like peptide-1--a new hormone and a new drug].
AB  - Glucagon-like peptide-1 (GLP-1 is an insulinotropic hormone, which is secreted
      from endocrine cells of the intestinal mucosa in relation to meal ingestion. It
      plays an important role as an incretin hormone; thus, mice with a null-muation in
      the gene encoding the GLP-1 receptor are glucose intolerant. In addition, GLP-1
      inhibits gastrointestinal secretion and motility and is thought to act as one of
      the hormones of the "ileal brake". The insulinotropic effect of GLP-1 is
      preserved in patients with non insulin-dependent diabetes mellitus (NIDDM) and,
      because GLP-1 also inhibits glucagon secretion, it effectively lowers blood
      glucose in such, and given as an intravenous infusion it may completely normalise
      blood glucose. Furthermore, because its actions on insulin and glucagon secretion
      are dependent on the blood glucose levels it will not cause hypoglycemia. Efforts
      are therefore currently being made to employ GLP-1 or analogues thereof in
      clinical diabetes treatment, not least because recent investigations have shown
      that GLP-1, perhaps due to its gastrointestinal actions, is capable of reducing
      food intake in humans.

PMID- 9571811
TI  - [Low birth weight is associated with non-insulin-dependent diabetes mellitus in
      discordant monozygotic and dizygotic twins].
AB  - Previous studies have demonstrated an association between low weight at birth and
      risk of later development of non-insulin dependent diabetes mellitus (NIDDM). It
      is unknown whether this association may be due to an impact of intrauterine
      malnutrition per se, or whether it may be due to a coincidence between the
      putative "NIDDM susceptibility genotype" and a genetically determined low weight
      at birth. We traced original midwife birthweight record determinations in a group
      of monozygotic (n = 14 pairs) and dizygotic (n = 14 pairs) twins who
      phenotypically appeared discordant for NIDDM at a mean age of 67 and 64 years
      respectively. Birthweights were lower in the NIDDM twins compared with both their
      identical and non-identical non-diabetic co-twins respectively (p < 0.02 both).
      Using a similar approach in twin pairs discordant for impaired glucose tolerance
      (IGT) per se, no significantly decreased birthweight was detected in the IGT
      twins compared with their non-diabetic co-twins. However, when a larger group of
      twins with different glucose tolerances were considered, birthweights were lower
      in twins with abnormal glucose tolerance including both NIDDM and IGT.
      Furthermore, the twins with the lowest birthweights among the two co-twins had
      the highest plasma glucose concentrations 120 min after the 75 g oral glucose
      load (n = 86 pairs, p = 0.02). The study supports the hypothesis that low
      birthweight and a non-genetically determined intrauterine component such af
      malnutrition may play a role for the development of NIDDM in twins.

PMID- 9571812
TI  - [Five-year survival in persons aged 40 years or over with newly diagnosed
      diabetes mellitus].
AB  - The five- to six-year all-cause mortality is analysed in 1323 newly diagnosed
      diabetic patients aged 40 years or over. The median age at diagnosis is lower for
      males (63.6 years) than for females (67.5 years), but more males (24.7%) than
      females (20.0%) have died (p = 0.04). This male excess mortality can mainly be
      attributed to the 60-79-year old males. With increasing diabetes duration both
      male and female diabetic patients exhibit an increasing excess mortality in
      comparison with the Danish population. For males this excess mortality becomes
      statistically significant four years after diagnosis for the 40-59 year-olds and
      after six years for the 60-79 year-olds. For females and very old males no
      statistically significant excess mortality is observed, but after two to four
      years there is a tendency for the survival curve of 40-79-year old females to
      separate from that of the Danish female population to show an excess mortality.
      In this population-based study the disadvantageous mortality experience of even
      newly-diagnosed diabetic patients is clearly demonstrated.

PMID- 9571813
TI  - [Long-term survival of patients with hypertension treated in general practice or
      at a specialized hypertension clinic. A 21-year observation study of 831 patients
      with hypertension].
AB  - This article is based on a study first published in Blood Pressure. After an
      initial diagnostic and therapeutic assessment at a specialized hypertension
      clinic, 831 patients with primary hypertension were during a 15-year period
      allocated to continuing managing care either by their general practitioner or by
      the hypertension clinic. Survival was assessed in the two groups: general
      practice (n = 437, 223 males, 214 females) and specialized hypertension clinic (n
      = 394, 208 males, 186 females). Median observation times for both groups were 11
      years. There were no significant differences between the groups concerning age at
      entry, pretreatment clinical status, pretreatment blood pressure or treated blood
      pressure level before allocation. Judged by a Cox' regression model, no
      difference in survival between the two groups could be registered. The leading
      cause of death in both groups was ischemic heart disease. Our results indicate
      that after the initial diagnostic assessment and adjustment of treatment,
      managing care in a specialized hypertension clinic offers no advantage concerning
      survival compared to managing care in general practice.

PMID- 9571814
TI  - [Admission pattern at a department of internal medicine. Factors of significance
      for readmission within three months after discharge].
AB  - The aim of the study was to investigate factors of significance for readmission
      of patients in a department of internal medicine. The study was based on hospital
      computerized data files. All admissions from the 1st of January to the 31st of
      December 1995 were included. During that period the department had 6061
      admissions of 4152 patients. The readmission rate was 1.46. All patients were
      followed three months after discharge. Within that period 1119 (27%) of the
      patients were readmitted. A high frequency of readmission was especially found
      within the first ten days after discharge. Length of stay in hospital did not
      influence readmission rate. Women, patients in the age group 71-90 years and
      patients with chronic diseases were more likely to be readmitted. The
      demonstrated factors relating to a high readmission rate are difficult to
      influence. A prospective study including the primary health care system and a
      clinical evaluation of the patients is needed to examine causes of the high
      number of readmission within the first ten days after discharge.

PMID- 9571815
TI  - [A lump in the breast. A rare first symptom of ovarian cancer].
AB  - The breast is an uncommon site for metastasis from extramammary primaries. A 43
      year-old woman presented with a lump in the left breast. A tumour with atypical
      microcalcifications was seen on the mammogram. Needle aspiration cytology
      revealed adenocarcinoma cells. The final histological diagnosis was papillary
      adenocarcinoma with psammoma bodies, probably secondary to an ovarian carcinoma.
      A bilateral carcinoma of the ovaries was subsequently diagnosed and treated. A
      mammary tumour with an atypical growth pattern and the absence of in situ
      carcinoma should always prompt the pathologist to considering the possibility of
      a metastatic tumour even though this is a rare occurrence. Earlier recognition of
      metastatic tumours to the breast may result in initiation of appropriate therapy
      and will preclude unnecessary surgical procedures.

PMID- 9571816
TI  - [John Travolta, Internet and a scandalous book review].

PMID- 9571817
TI  - [Urinary incontinence--not the same we are talking about].

PMID- 9571818
TI  - [Lung cancer, tobacco and environment].

PMID- 9571819
TI  - [Is it treatment with paracetamol in severe pain reasonable?].

PMID- 9571820
TI  - [Basic considerations in connection with malaria prophylaxis].

PMID- 9571821
TI  - [Malaria prophylaxis].

PMID- 9571822
TI  - [Boron poisoning].

PMID- 9571823
TI  - Immediate molar implant placement and prosthetic restoration after extraction.
      Case report.

PMID- 9571824
TI  - Traumatic injury to the anterior mandible restored with endosseous implants.

PMID- 9571825
TI  - Concepts in impressions for dental implantology.

PMID- 9571826
TI  - Fully edentulous case treatment plan: bar supported overdentures. Case report-
      Part II.

PMID- 9571827
TI  - The importance of asepsis in dental implantology.
AB  - All surgical procedures, including dental implantation, involve certain risk
      factors. One of the most common is that of postoperative infection. The harsh
      realities of today's medical environment such as the threat of blood-borne
      pathogens and transmittable infections, the increased cost of hospitalization,
      and the increase in malpractice suites against surgeons, make it imperative that
      all surgeons follow safe and sterile surgical protocols that reduce the chances
      of infections and ensure satisfactory results.

PMID- 9571828
TI  - Single implant replacement of a first bicuspid. A case report.

PMID- 9571829
TI  - Apicoectomy of a root form implant. Case report.

PMID- 9571830
TI  - R.A.P.I.D. Reconstructive alternative for prosthetics in implant dentistry.
AB  - As stated at the outset, this technique is not for every case. Each case must be
      selected with great care, consideration and careful planning. In concert with
      observing the Implant Lighthouses, this technique can produce a successful case.
      It can be done to save time, without compromising the prescribed techniques and
      quality.

PMID- 9571831
TI  - Restoration of the posterior maxillary arch--an implant supported fixed
      prosthetic alternative.

PMID- 9571832
TI  - Premaxilla restoration following a traumatic injury. Pictorial case presentation.

PMID- 9571833
TI  - Yellow Pages: the cornerstone for "professional" advertising.

PMID- 9571834
TI  - The triangle of bone--a formula for successful implant placement and restoration.

PMID- 9571835
TI  - Radiographic modalities for diagnosis and treatment planning in implant
      dentistry.
AB  - Early in the development of implant technology it became apparent that
      conventional dental imaging techniques were limited for evaluating patients for
      implant surgery. During the treatment planning phase, the recipient bed is
      routinely assessed by visual examination and palpation, as well as by periapical
      and panoramic radiology. These two imaging modalities provide a two-dimensional
      image of mesial-distal and occlusal-apical dimensions of the edentulous regions
      where implants might be placed. When adequate occlusal-apical bone height is
      available for endosteal implants, the buccal-lingual width and angulation of the
      available bone are the most important criteria for implant selection and success.
      However, neither buccal-lingual width nor angulation can be visualized on most
      traditional radiographs. Although clinical examination and traditional
      radiographs may be adequate for patients with wide residual ridges that exhibit
      sufficient bone crestal to the mandibular nerve and maxillary sinus, these
      methods do not allow for precise measurement of the buccolingual dimension of the
      bone or assessment of the location of unanticipated undercuts. For these
      concerns, it is necessary to view the recipient site in a plane perpendicular to
      a curved plane through the arch of the maxilla or mandible in the region of the
      proposed implants. Implant dentists soon recognized that, for optimum placement
      of implants, cross-sectional views of the maxilla and mandible were the ideal
      means of providing necessary pre-operative information. Today, the two most often
      employed and most applicable radiographic studies for implant treatment planning
      are the panoramic radiograph and tomography. Although distortion can be a major
      problem with panoramic radiographs, when performed properly they can provide
      valuable information, and are both readily accessible and cost efficient. To help
      localize potential implant sites and assist in obtaining accurate measurements,
      it is recommended that surgical stents be used with panoramic radiographs. In
      simple cases, where a limited number of implants are to be placed, panoramic
      radiography and/or tomography may be used to obtain a view of the arch of the jaw
      in the area of interest. For complex, cases, where multiple implants are
      required, the CT scan imaging procedure is recommended. Because of its ability to
      reconstruct a fully three dimensional model of the maxilla and mandible, CT
      provides a highly sophisticated format for precisely defining the jaw structure
      and locating critical anatomic structures. The use of CT scans in conjunction
      with software that renders immediate "treatment plans" using the most real and
      accurate information provides the most effective radiographic modality currently
      available for the evaluation of patients for oral implants. To follow patients
      after implant surgery, DSR can be helpful by addressing the limitations of other
      radiographic modalities in detecting postoperative changes. By eliminating
      unchanged information, DSR allows the clinician's eye to focus on actual changes
      that have occurred between the recordings of two images.

PMID- 9571836
TI  - The milled bar overdenture prosthesis.

PMID- 9571837
TI  - Legal perspectives: I. Doctors versus lawyers. II. An accident waiting to happen
      ... local anesthetics.

PMID- 9571838
TI  - Ridge preservation: the new buzzword in dentistry.
AB  - The viability of Ridge Preservation as achieved by practicing Advanced Extraction
      Therapy (AET) and Replacement Therapy (R.T.), will impact the future practice of
      Dentistry. With the availability of clinically proven materials such as implants
      (titanium) and synthetic bone substitutes (Bioplant HTR), a practical solution
      exists to solve a very old clinical problem. Treatment modalities are available
      today making the atrophic jaw-bone a malady of the past. Imagine no more "dental
      cripples," and no more inadequate bone situations for implant placements. Ridge
      Preservation and Replacement Therapy should be practiced regularly: "when we take
      something out, we should put something back." Our practices will grow. Our
      patients will thank us.

PMID- 9571839
TI  - Using bioengineering as a tool for dental case planning.

PMID- 9571840
TI  - Avoiding implant overload.
AB  - Implant overload can be caused by a great number of factors, including suboptimal
      implant design and size; an insufficient number of implants to support the
      restoration; improperly splinted abutments; violation of conventional prosthetic
      limitations for natural dentition; excessively cantilevered pontics; splinting to
      natural dentition, even with a stress-breaking attachment; improperly positioned
      implants; the wrong type of restoration for the clinical condition; loss of
      supporting bone; excessive parafunctional forces; and non-maintenance of the
      components. Screws loosening or crestal bone loss are frequently the first
      detectable signs of implant overload, and warrant immediate action. Other signs
      of occlusal overload include infection, inflammation and peri-implant
      radiolucency. Balancing the whole arch, reducing contacts and surface area of the
      implant-supported areas, and shortening or eliminating cantilevers whenever
      possible are initial steps that can be taken to eliminate or lessen the excessive
      stress. The strongest possible implant and restorative materials should be used,
      and the patient should also be instructed as to proper implant function. As oral
      implantology develops at a seemingly exponential rate, it is extremely important
      to keep abreast of the latest advancements. Overload, rather than component
      design, is the primary factor in the majority of prosthetic and implant failures.
      Safeguarding the long-term integrity of the restoration should be a shared
      responsibility involving the patient and the health care team.

PMID- 9571841
TI  - Two-stage basket-design implant matures with the industry.

PMID- 9571842
TI  - "What is the single most important aspect of implant dentistry"?
AB  - The world of implant dentistry is exciting and challenging. We are all on the
      great learning curve of excellence. With careful planning, and knowledge of the
      anatomical structures which are missing, we have in our hands the ability to
      create reproductions which are indistinguishable from nature. Remember, the tooth
      is the goal, not the implant!

PMID- 9571843
TI  - Surgical technique of onlay bone grafting.
AB  - Different forms of bone grafting materials are alluded to in this paper.
      Autogenous graft is superior to other bone grafting materials but is many times
      not available or the patient is not willing to utilize cranial or iliac crest
      bone. Allografts, Xenografts and bone substitute materials are the most widely
      used today in dentistry and especially those patients wishing to use dental
      implants as abutment support. The technique discussed utilizing surgical tissue
      design, tissue closure over the graft material and the tissue barrier can be used
      to produce a successful final result using a graft material of choice. It is
      quite certain that in the near future, the use of bone graft enhancement
      materials (bone morphogenic protein-like substances) will be used to enhance a
      quicker result. It is anticipated that growth factors, stimulating factors, bone
      morphogenetic proteins, and osteogenetic proteins will cause a bone graft to
      vascularize, solidify, incorporate, and function optimally in a shorter period of
      time. These materials will reduce the disability time and enhance the outcome of
      bone grafting in the dental profession. It is also anticipated that advanced
      tissue surgical techniques will give better vascularization to the new graft. The
      described technique is predictable and should give the operator the desired
      result.

PMID- 9571844
TI  - Combining osseointegrated implants and natural teeth to rehabilitate partially
      edentulous patients.

PMID- 9571845
TI  - Potential problem areas in dental implants.

PMID- 9571846
TI  - Introverted marketing: how to keep dental implants a secret.

PMID- 9571847
TI  - Root form implants for tomorrow.
AB  - However, accepting the route of dental implantology's evolution, and with a
      positive outlook for the future, the author believes that the four types of root
      form implants described here will be utilized. This belief in their application,
      has come from vast experience placing thousands of implants into various types of
      bone. It is now up to those dentists who have become exclusively involved with
      one type of root form implant to reflect on the ideas expressed in this article,
      and start to challenge what has been considered the "norm", and consider treating
      their patients with implants that will most likely prove to be superior in design
      and function.

PMID- 9571848
TI  - Implant marketing: cost effective implant dentistry.
AB  - The application of the KAL-Technique to the field of implant dentistry allows
      both patients and dental practices to benefit. It is an exciting advance that
      decreases frustration and stress in providing implant procedures and lowers
      overall costs. Professionals using the KAL-Technique report significant
      predictability in achieving passive framework fit. They are also lowering overall
      cost of implant cases, which increases the number of patients who can accept
      implant treatment. It has been well established that the more individuals in a
      practice that receive implants, the more referrals a practice will gain. This is
      because implant patients find tremendous advances in the quality of life, and do
      not hesitate to tell others who can take advantage of this opportunity. Implant
      dentistry is one of the fastest growing fields in dentistry today. While some
      other areas of dentistry begin to decline in volume and need, implant dentistry
      provides the opportunity to keep practices strong and to insure long-term
      success.

PMID- 9571849
TI  - Implant identification card & maintenance form.

PMID- 9571850
TI  - Legal perspectives--risk management considerations: I. Duty of care--drug
      prescription. II. F.D.A. considerations for dentists and auxiliary staff. III.
      Expert testimony letter.

PMID- 9571851
TI  - Implant marketing: marketing with newsletters. The informed patient, referring
      dentist, prospect, etc.

PMID- 9571852
TI  - A case study. Ridge-lapped implants: can they be used?

PMID- 9571853
TI  - Retrofitting dental implants to existing fixed partial dentures.

PMID- 9571854
TI  - From blade vent to subperiosteal to osseointegration: one patient's 19 year
      experience.

PMID- 9571855
TI  - Treatment of trauma-related bony defects with nonresorbable hydroxylapatite.

PMID- 9571856
TI  - Proper articulation essential for implant success.

PMID- 9571857
TI  - Legal perspectives: I. Practicing medicine without a license. II. Good
      samaritans.

PMID- 9571858
TI  - Differential diagnosis in dentistry.

PMID- 9571860
TI  - Roentgen ray anomalies. "Dental-related sinus pathosis".

PMID- 9571859
TI  - Benton E. Crawford radiograph of the month. Odontogenic myxoma.

PMID- 9571861
TI  - Alveolar bone augmentation materials.

PMID- 9571862
TI  - Office embezzlement: is your practice a target?

PMID- 9571863
TI  - C&B Metabond--clinical applications (II).

PMID- 9571864
TI  - Reduction copings.

PMID- 9571865
TI  - Differential diagnosis in dentistry. Drug-related gingival hyperplasia.

PMID- 9571866
TI  - Benton E. Crawford radiograph of the month. Osteopetrosis.

PMID- 9571867
TI  - Roentgen ray anomalies. "Radiolucency of the anterior maxilla".

PMID- 9571868
TI  - Review of dentin bonding agents.

PMID- 9571869
TI  - Still sending statements? Why?

PMID- 9571870
TI  - C&B Metabond--clinical applications (III).

PMID- 9571871
TI  - A clinical trial of implant prostheses: performance and preference.

PMID- 9571873
TI  - Benton E. Crawford radiograph of the month. Nasopalatine duct cyst.

PMID- 9571872
TI  - Differential diagnosis in dentistry. Oral lipoma.

PMID- 9571874
TI  - Roentgen ray anomalies. "Horizontal (Le Fort I) maxillary fracture complications
      from kidney transplant surgery".

PMID- 9571875
TI  - Vitiligo.

PMID- 9571876
TI  - A renaissance of freehand bonding.

PMID- 9571877
TI  - Amalgambond--clinical applications (II).

PMID- 9571878
TI  - Osseointegrated dental implants.

PMID- 9571879
TI  - Differential diagnosis in dentistry. Nicotinic stomatitis.

PMID- 9571880
TI  - Benton E. Crawford radiograph of the month. Osteoradionecrosis.

PMID- 9571881
TI  - Roentgen ray anomalies. "Unilateral orbital blow-out fracture".

PMID- 9571882
TI  - Herpes simplex virus type 1 infections.

PMID- 9571884
TI  - Amalgambond--clinical applications (I).

PMID- 9571883
TI  - Nutrition and wound healing.

PMID- 9571885
TI  - Osseointegrated dental implants.

PMID- 9571886
TI  - Decreasing levels of fluoridation in the municipal water supply over the past six
      consecutive years.

PMID- 9571887
TI  - Antibiotic prophylaxis for dental patients with total joint replacements.
      American Dental Association; American Academy of Orthopaedic Surgeons.
AB  - An expert panel of dentists, orthopaedic surgeons, and infectious disease
      specialists, convened by the American Dental Association and the American Academy
      of Orthopaedic Surgeons, or AAOS, performed a thorough review of all available
      data to determine the need for antibiotic prophylaxis to prevent hematogenous
      prosthetic joint infections in dental patients who have undergone total joint
      arthroplasties. The result is this report, which has been adopted by both
      organizations as an advisory statement. The panel's conclusion. Antibiotic
      prophylaxis is not indicated for dental patients with pins, plates and screws,
      nor is it routinely indicated for most dental patients with total joint
      replacements. However, it is advisable to consider premedication in a small
      number of patients (Table 1) who may be at potential increased risk of
      hematogenous total joint infection.

PMID- 9571888
TI  - Kansas Dental Impaired Provider Program. Confidential help for addicted dentists.
      "One man's cry for help".

PMID- 9571889
TI  - How common is oral cancer in Kansas?

PMID- 9571891
TI  - The use of a prosthetic appliance to manage a large palatal defect in a dog.
AB  - Large defects of the hard palate can result from a congenital abnormality,
      trauma, or surgical treatment of oral masses. Closure of these defects can be
      challenging as dehiscence is common. Large, inoperable hard palate defects may be
      managed with prosthetic obturators, which recreate the separation between the
      oral and nasal cavities. This report describes the use of a palatal obturator to
      manage a large palatal defect that persisted after resection of a palatal
      fibrosarcoma. Three prior attempts at surgical closure of the defect had failed.

PMID- 9571890
TI  - Drug-induced gingival overgrowth after phenytoin and nifedipine therapy. A case
      report.

PMID- 9571892
TI  - Use of a resin-ionomer in crown-root fracture repair of a canine tooth of a dog.
AB  - A resin-ionomer material was used to repair a longitudinal sub-crestal crown-root
      fracture of a maxillary canine tooth of a young dog. Infinity, the resin-ionomer
      used in this report, has been shown in human studies to be biocompatible with
      soft and osseous tissues, making it appropriate for use as a subgingival
      restorative material. The tooth was treated endodontically to achieve
      apexification, followed by conventional endodontic treatment, crown-root fracture
      repair, and preparation for placement of an Inceram crown.

PMID- 9571893
TI  - Use of the dental pulp tester in veterinary dentistry.
AB  - Personal experience with a manually set electronic dental pulp tester is
      described. The small battery-operated hand-held unit is used in awake dogs and
      cats, and can rapidly indicate absence of vitality or increased or decreased
      responsiveness of the pulp tissue.

PMID- 9571894
TI  - Use of videofluoroscopy in zoo dentistry: endodontic procedure in a tiger.
AB  - Videofluoroscopy was used as a radiographic technique to visualize a canine tooth
      during root canal therapy in a Siberian tiger. Videofluoroscopy was useful
      because the procedure was performed in a zoo setting with no access to an on-site
      darkroom. The fluoroscopic screen and videotape allowed for immediate viewing of
      the root canal system.

PMID- 9571895
TI  - Non-apical root canal ramifications in the teeth of dogs.
AB  - The roots of 130 extracted teeth were examined for non-apical ramifications from
      the main canal. Following decalcification and dehydration, the root canals were
      identified with an Indian ink gel. Secondary canals were found in 4 of the 130
      teeth (2.4%), and stumps that may represent incomplete lateral canals were
      identified in two teeth. We conclude that non-apical root canal ramifications are
      much less common in dogs compared to humans.

PMID- 9571896
TI  - Understanding dental plaque; biofilm dynamics.
AB  - A biofilm is a well organized community of cooperating microorganisms. Biofilms
      predictably form in nature, in artificial environments, and on medically
      implanted prostheses and indwelling venous catheters. They also form on tooth
      surfaces in the form of dental plaque. The intent of this article is to aid in
      the understanding of dental plaque by exploring biofilm structure, nature and
      dynamics. Understanding plaque facilitates its treatment and control.

PMID- 9571897
TI  - Surgical management of the tight lip syndrome in the Shar-Pei dog.
AB  - The lower lip in some Shar-Pei puppies curls up over the mandible, causing
      lingual displacement of the incisor and canine teeth and may result in
      interference with the natural growth of the mandible. Surgical correction of this
      defect at the proper age can allow the mandible to grow normally and avoid
      development of an uncomfortable mouth. Two methods of correction are described.
      Cheiloplasty has been used by the author on 99 puppies over a 10 year period,
      only two of which were returned for additional surgery because the result was
      inadequate; the cheiloplasty procedure was repeated in these two dogs. Excision
      of an elliptical section of the skin of the chin was performed once during the
      same 10 year period.

PMID- 9571898
TI  - Aging horses by examining the teeth--a centuries-old inexact science. Special
      report.

PMID- 9571899
TI  - Dental plaque flora of the dog with reference to fastidious and anaerobic
      bacteria associated with bites.
AB  - Animal bite wounds are amongst the most common types of traumatic injuries in
      humans. The organisms isolated from these wounds generally reflect the oral flora
      of the biting animal, and may be fastidious in nature and difficult to identify.
      This study was undertaken to determine the prevalence of Eikenella corrodens,
      Actinobacillus actinomycetemcomitans, Porphyromonas and Prevotella spp. in
      supragingival dental plaque collected from the right maxillary canine and
      carnassial teeth and the right mandibular canine tooth of dogs. In part one of
      the study, 30 dogs were used. E. corrodens was found in 62% of these dogs and 44%
      of individual plaque samples. A. actinomycetemcomitans was not detected in any of
      the dogs sampled. In part two, 34 dogs were used to determine the prevalence of
      the black pigmented anaerobic bacilli (Porphyromonas and Prevotella spp.).
      Porphyromonas gingivalis was present in 68% of these dogs and 47% of individual
      plaque samples. Prevotella intermedia was present in 44% of the dogs and 23% of
      individual plaque samples. The recently described Porphyromonas canoris,
      Porphyromonas salivosa, Porphyromonas cangingivalis, Porphyromonas cansulci,
      Porphyromonas crevioricanis and Prevotella denticola species were isolated from
      only 9%, 6%, 3%, 3%, 3% and 3% of dogs respectively. Porphyromonas gingivicanis
      was not isolated from any of the animals sampled. In conclusion, black-pigmented
      anaerobic bacilli were isolated from 91% of the animals sampled and therefore
      constitute a significant risk with respect to bite wound infections. It is also
      suggested that the prevalence of E. corrodens in wound infections has been
      underestimated in previous reports because of use of inappropriate techniques for
      detecting this organism.

PMID- 9571900
TI  - Restorative dental treatments of abraded canine teeth in a Sumatran tiger
      (Panthera tigris sumatrae).
AB  - A Sumatran tiger had developed severely abraded canine teeth by biting on cage
      bars. This resulted in weakening and marked sensitivity of the teeth. Indications
      for, techniques of and complications of restorative dental treatments are
      described. The outcome of different restorative dental treatments indicates that
      endodontic treatment should be carried out first if the fracture of a weakened
      tooth is anticipated. To improve retention, the acid-etch technique is preferred
      in combination with macroretentive preparations. In this case, amalgam was used
      successfully in combination with composite resin to restore function to a canine
      tooth with a large distal defect.

PMID- 9571901
TI  - Anatomical variations in the dentition of the domestic cat.
AB  - Skulls (n = 155) of adult domestic cats were examined macroscopically and
      anatomical variations were documented. The maxillary second premolar tooth was
      absent in 7.9% of cases, and was found to have a single root in 27.7%, partly
      fused roots in 55.1% and two fully formed roots in 9.2% of cases. The maxillary
      first molar tooth was absent in 2.3% of cases; a single root was present in
      35.0%, a partly fused root in 34.7%, and two roots in 28.0% of cases.
      Supernumerary roots were found on the maxillary third premolar teeth in 10.3% of
      cases. Other variations were found to be extremely rare.

PMID- 9571902
TI  - Evaluation of Bioglass/PerioGlas (Consil) synthetic bone graft particulate in the
      dog and cat.
AB  - This paper describes the use of Bioglass synthetic bone graft particulate
      (PerioGlas/Consil) in the treatment of osseous periodontal defects, and in post
      extraction sites to maintain the vertical height and width of the alveolar ridge.
      The material is easy to use, inhibits epithelial down-growth, and acts as a
      mechanical hemostatic agent. Radiographic follow up in 36 dogs and 5 cats
      demonstrated significant bone fill. In the osseous periodontal defect treatment
      group, clinical probing depths decreased significantly, and there was an apparent
      gain in attachment level.

PMID- 9571903
TI  - "Will you stand behind your work"?

PMID- 9571904
TI  - "Skip the gum work and start the bridges".

PMID- 9571905
TI  - "Conflict, collusion or collaboration: who benefits from a referral"?

PMID- 9571906
TI  - Patient's (fraudulent) request.

PMID- 9571907
TI  - 1996 Kentucky Dental Practice Survey.

PMID- 9571908
TI  - The dental assistant and substance abuse.

PMID- 9571909
TI  - Failed endodontic post: discovering a more successful procedure.

PMID- 9571910
TI  - Severe pernicious anemia presenting with burning mouth symptoms.

PMID- 9571911
TI  - Guest clinician: implant terminology.

PMID- 9571912
TI  - Treatment of the HIV-infected patient. Part 1: Risk reduction.

PMID- 9571913
TI  - Study: physicians missing HIV signs.

PMID- 9571914
TI  - Digital x-ray imaging: a diagnostic aid for the clinician and a technological
      instrument for the researcher.
AB  - Digital x-ray imaging is a relatively new technology which may have potential for
      both the oral health care practitioner and the oral researcher. The ability to
      acquire low x-ray dose images is extremely important to patient care.
      Additionally, the ability to manipulate these images provides valuable clinical
      and research information which can enhance overall patient care.

PMID- 9571915
TI  - Oral complications associated with the use of immunosuppressive agents in a renal
      transplant patient.

PMID- 9571916
TI  - Completely submerged primary molars.
AB  - Two mixed dentition cases have been presented which became quite complicated
      because of ankylosed and submerged primary second molars. These cases demonstrate
      the need for an early orthodontic evaluation and interceptive orthodontics. The
      orthodontic and surgical procedures required for these two patients could have
      easily been avoided by removing the ankylosed primary molars and placing space
      maintainers. (Of course this depends upon the parents responding to their dental
      recall notices.) If a submerging primary molar is retained too long, the second
      premolar may become displaced superiorly and the permanent first molar may
      migrate mesially as it erupts. Both of these problems can be prevented by
      extracting the ankylosed primary second molar before it submerges below the
      mesial height of contour of the permanent first molar. A fixed space maintainer
      then becomes necessary to prevent loss of arch length by mesial migration of the
      permanent molar.

PMID- 9571917
TI  - Surgical site preparation for a single-tooth implant restoration.

PMID- 9571918
TI  - "Why am I not doing more implant cases"?

PMID- 9571919
TI  - Intraoral Kaposi's sarcoma associated with alveolar bone erosion.

PMID- 9571920
TI  - Guest clinician: an alternative treatment of RAU (recurrent apthous ulcers).

PMID- 9571921
TI  - Treatment of the HIV-infected patient. Part II: Treatment overview.

PMID- 9571922
TI  - Legal implications of hiring and terminating employees.

PMID- 9571924
TI  - Achieving the perfect relationship. What dental hygienists expect from their
      employers.

PMID- 9571923
TI  - Distance learning: an idea that may change the face of dentistry.

PMID- 9571925
TI  - Policies regarding HIV-positive and AIDS patients.

PMID- 9571926
TI  - Monitoring sterilization services.

PMID- 9571927
TI  - Flood damaged hazardous materials require special attention.

PMID- 9571928
TI  - Update on vital tooth bleaching.

PMID- 9571929
TI  - Clinical pathology case conference. Lentigo maligna melanoma.

PMID- 9571930
TI  - James Baxter Bean: the first military maxillofacial hospital.

PMID- 9571931
TI  - Treatment of the adverse effects of contrast media.
AB  - Although low-osmolar contrast media are relatively safe, a moderate non-life
      threatening reaction requiring some treatment does occur in 0.2-0.4% of patients.
      A severe life-threatening reaction can be expected in 0.04% of patients. Prompt
      recognition and treatment are invaluable in blunting the adverse response of a
      patient to radiographic contrast material and may prevent the reaction from
      becoming severe or even life-threatening. Radiologists and their staff should
      review treatment protocols regularly so that each can play his/her role
      efficiently. Knowledge, training, and preparation are crucial for guaranteeing
      appropriate and effective therapy in the event of an adverse contrast-related
      event. On the basis of a review of the literature, we suggest a treatment
      protocol.

PMID- 9571932
TI  - Frequency of late allergy-like adverse reactions following injection of
      intravascular non-ionic contrast media. A retrospective study comparing a non
      ionic monomeric contrast medium with a non-ionic dimeric contrast medium.
AB  - PURPOSE: A retrospective study was undertaken of the late adverse reactions
      following the injection of contrast media. The purpose was to determine whether
      there was a difference between non-ionic monomeric (iohexol) and non-ionic
      dimeric (iodixanol) contrast media in the reactions produced. MATERIAL AND
      METHODS: A total of 3,408 patients were sent a written questionnaire in which
      they were asked to confirm or deny any subjective discomfort or adverse event
      during a period of one hour to one week after a previous radiological examination
      with contrast medium. Patients who had undergone angiography (i.v. or i.a.
      injection) and CT (i.v. injection) were included. Objective signs of an allergy
      like reaction were listed and the patients were asked to subjectively quantify
      any consequent discomfort. RESULTS: The compliance rate was 84%. Of the 3075
      injections finally included in the study, 133 (4.3%) had resulted in contrast
      medium-related adverse reactions of which 72 (2.3%) were immediate and 61 (2%)
      were late. Iohexol induced late reactions in 14/851 (1.7%) cases, and iodixanol
      in 24/1218 (2.0%) cases following i.v. injection and in 23/1006 (2.3%) cases
      following i.a. injection. The differences were not significant. There were no
      differences between the two contrast media in the subjective rating of discomfort
      except that the patients who had received iodixanol also had the highest
      individual-intensity score. No patient had been hospitalized owing to an adverse
      reaction and all reactions had been regarded as mild or moderate. CONCLUSION: The
      number of late adverse reactions was low. There was no difference in the
      frequency of the late adverse reactions following i.v. injection between
      iodixanol and iohexol. There was also no difference in the reactions between the
      i.a. and i.v. injections of iodixanol.

PMID- 9571933
TI  - Gd-DTPA as an alternative contrast agent in conventional and interventional
      radiology.
AB  - PURPOSE: Patients with contra-indications to iodine-based contrast media present
      problems in radiological examination. In this study, we evaluated Gd-DTPA as an
      alternative contrast agent in conventional and interventional radiology. MATERIAL
      AND METHODS: The undiluted contrast agent Gd-DTPA meglumine (469 mg/ml,
      Magnevist) was used in 10 examinations in 8 patients. A dosage of 20-45 ml was
      used in 5 conventional studies: endoscopic retrograde cholangiography,
      cystography, urethrocystography, and 2 retrograde pyelographies. A dosage of 10
      120 ml was used in 5 interventions: 1 percutaneous nephrostomy, and 4 biliary
      tract drainages. RESULTS: The image quality was adequate in all studies. No
      adverse pharmacological reactions occurred; however, there was renal
      extravasation of Gd-DTPA which did cause temporary pain in 1 patient at bilateral
      retrograde pyelography. CONCLUSION: Gd-DTPA may be used as an alternative
      contrast medium in selected conventional and interventional roentgenological
      studies when iodine is contra-indicated.

PMID- 9571934
TI  - Malignant glioma. Evaluation with 3D time-of-flight MR angiography.
AB  - PURPOSE: To investigate the clinical utility of 3D time-of-flight (TOF) MR
      angiography (MRA) in the evaluation of pathological vessels in patients with
      malignant glioma. MATERIAL AND METHODS: Sixteen patients with malignant glioma
      (12 with glioblastoma multiforme and 4 with anaplastic astrocytoma) were examined
      with 3D TOF MRA before and after the injection of gadopentetate dimeglumine. The
      3D TOF MRA study was compared with conventional angiography in all patients.
      RESULTS: The unenhanced 3D TOF MRAs successfully depicted the feeding arteries in
      9 patients but failed to depict small feeding arteries in 2 patients in whom
      these arteries were shown by conventional angiography. The enhanced MRAs
      demonstrated draining veins from the lesions in 8 patients but failed to depict a
      draining vein in 1 patient that was shown by conventional angiography. The
      stereoscopic view projection effectively depicted displacements of the major
      cerebral arteries in 14 patients, and deep venous structures in 11 patients which
      almost accorded with the findings at conventional angiography. CONCLUSION: Our
      results indicate that 3D TOF MRA can provide an accurate visualization of
      pathological vascular structures and thus help establish a diagnosis in patients
      with malignant glioma.

PMID- 9571935
TI  - Three-dimensional spiral CT angiography in the detection of cerebral aneurysm.
AB  - PURPOSE: The value of CT angiography in the detection and evaluation of aneurysms
      was compared to digital subtraction angiography (DSA). MATERIAL AND METHODS:
      Seventeen patients with acute subarachnoid hemorrhage (SAH) or with known or
      suspected aneurysm were investigated by means of spiral CT angiography, which
      included 3D reconstruction. These findings were compared with those at DSA.
      RESULTS: In 16 patients, 20 aneurysms were found; the remaining patient had an
      ectatic vessel that simulated an aneurysm. Seventeen of the angiographically
      proved aneurysms were detected at CT angiography (sensitivity 85%). One further
      aneurysm was identified retrospectively as the result of greater experience in
      the method. All the aneurysms that escaped detection at CT were 3 mm in size. All
      the vessels of the circle of Willis, except for the posterior communicating
      artery, were properly evaluated at CT angiography. Difficulties were encountered
      in assessing the posterior communicating artery and the extradural segment of the
      internal carotid artery owing to their close spatial relationship to the bony
      structures of the skull base and the cavernous sinus. CONCLUSION: CT angiography
      is a low-risk technique with a low level of invasiveness that is useful in
      following up known aneurysms. The 3D reconstruction yields further topographic
      information that helps in the planning of endovascular or surgical intervention.
      The facility for rotating the reconstructed vessels and displaying them from
      different angles is of particular value in cases difficult to assess at
      angiography.

PMID- 9571936
TI  - Increased accuracy in MR diagnosis of uveal melanoma by carbohydrate loading. A
      simple method that reflects rapid metabolic change.
AB  - PURPOSE: To evaluate patients with clinically diagnosed uveal melanoma. MATERIAL
      AND METHODS: Forty-eight consecutive patients were examined with spin-echo (SE)
      and fast spin-echo (FSE) MR sequences that utilized glucose-fructose enhancement
      together with a subtraction technique on a 1.5 T unit. RESULTS: Twenty-seven
      patients were enucleated and the eyes histologically examined for tumours
      (spindle cell, mixed cell, and epitheloid cell). The remaining patients were
      referred for other treatment. There were no significant differences in T2
      although T2 was longer in the amelanotic lesions. Carbohydrate loading in
      combination with a subtraction technique gave: an increased signal intensity; a
      prolongation of T2; and an increased tumour size. The FSE sequences were as good
      as the SE sequences in the visualization of uveal malignant melanoma. CONCLUSION:
      MR imaging performed with carbohydrate loading registers metabolic changes
      induced in the tumour. This gives the method great validity in the diagnosis of
      uveal melanoma. The method is especially useful in amelanotic tumours that have
      longer relaxation times than melanotic tumours. The SE technique can be replaced
      with the FSE technique.

PMID- 9571937
TI  - Optic neuritis. Doppler ultrasonography compared with MR and correlated with
      visual evoked potential assessments.
AB  - PURPOSE: To establish the role of Doppler ultrasonography (US) in the examination
      of patients with acute unilateral optic neuritis. MATERIAL AND METHODS: Twenty
      five patients with a clinical diagnosis of optic neuritis were prospectively
      evaluated and 18 of them were included in the study. The inclusion criteria were
      MR findings of unilateral disease and age below 50 years. All patients were
      examined with MR in order to objectively detect, localize and measure the optic
      nerve lesions and in order to exclude patients with unidentifiable optic nerve
      involvement. Evaluation with US was performed to determine nerve morphology,
      nerve swelling, and resistance to flow in the central retinal artery. The
      patients' contralateral optic nerve served as an internal control. The US
      findings were correlated to the degree of visual impairment, both initially and
      at follow-up. Visual evoked potential (VEP) assessments were also performed in 16
      patients. RESULTS: A statistically significant difference was found in the optic
      nerve diameter and in the resistance to flow in the central retinal artery
      between the affected and unaffected eyes. Patients with a prolonged impairment of
      visual acuity initially had a more swollen nerve and an increased resistance to
      flow in the affected optic nerve. Prognostic information was also gathered solely
      by evaluating the unaffected nerve diameter: patients who normally had thinner
      optic nerves had a more severe form of optic neuritis. VEP assessments were
      positive in all patients investigated. CONCLUSION: Doppler US can be used
      together with a VEP assessment as an indicator of the disease process in acute
      optic neuritis. These methods offer a potential for monitoring patients over
      time.

PMID- 9571938
TI  - Dedicated head-neck coil in MR angiography of the supra-aortic arteries from the
      aortic arch to the circle of Willis.
AB  - PURPOSE: To evaluate the usefulness of a dedicated head-neck coil in preoperative
      imaging of the supra-aortic arteries. MATERIAL AND METHODS: Forty consecutive
      patients with suspected carotid artery stenosis underwent MR angiography (MRA).
      Using a dedicated head-neck coil, we made a complete evaluation of the supra
      aortic arteries and graded the internal carotid artery (ICA) stenoses. MRA was
      performed at 1.5 T with: coronal 3D FISP from the aortic arch to the circle of
      Willis; transverse 2D FLASH and 3D TONE of the carotid bifurcation; transverse 3D
      TONE of the carotid siphon and the circle of Willis; and transverse 3D FISP of
      the aortic arch. I.a. digital subtraction angiography (DSA) was used as the
      reference. ICA stenoses of 70% and more at DSA (NASCET methodology) were regarded
      as severe. RESULTS: Severe ICA stenoses were detected with high sensitivity and
      specificity: 93% and 92% respectively for coronal 3D FISP; 90% and 85%
      respectively for transverse 2D FLASH; and 97% and 94% respectively for transverse
      3D TONE. The carotid siphon and the intracranial ICA were best depicted by 3D
      TONE. None of the applied sequences gave a satisfactory visualization of the
      aortic arch or of the origins of the vertebral arteries. CONCLUSION: With the
      head-neck coil, the supra-aortic arteries (including the intracranial vessels)
      were visualized without the need to reposition the patient, but depiction of the
      aortic arch was not acceptable. The quantification of ICA stenoses was reliable.

PMID- 9571939
TI  - Multiplanar and 3D CT of acetabular fractures.
AB  - PURPOSE: To establish a standard protocol for the multiplanar (MPR) and 3D shaded
      surface display (SSD) reconstruction of CT data on acetabular fractures, and to
      assess the usefulness of these reformats. MATERIAL AND METHODS: Acetabular
      fractures in 15 patients were imaged by means of plain radiographs, transaxial
      CT, MPR reformats, and SSD reformats. RESULTS: The classification of the
      acetabular fracture was revised in 7/15 cases when the transaxial CT images were
      read after the plain radiographs. Although the MPR and SSD reformats did not
      alter the classification, they did add to the degree of confidence in the
      diagnosis in 9/15 cases. In 2 patients, the MPR and SSD reformats indicated
      operative instead of conservative treatment. In the MPR reformats, the following
      views were considered essential in all cases: (a) along the anterior column; (b)
      along the posterior column; and (c) along both columns and the inferior ramus. In
      the SSD reformats, the following views were considered essential in all cases:
      (d) the latero-caudal en face view into the acetabulum; and 180 degrees opposite
      to this, (e) the medio-cranial view (facing the quadrilateral plate). In 10/15
      cases, these views were all that was needed for classification. It was, however,
      essential to remove the femur from the images before reconstructing the SSD
      views. CONCLUSION: Complex acetabular fractures with displacement should be
      evaluated by means of transaxial CT and additional MPR and SSD reformats. The use
      of appropriate standard MPR and SSD views shortens the time required to produce
      the reformats and thereby maximizes the benefit gained.

PMID- 9571940
TI  - The role of CT in the diagnosis of sacro-iliitis.
AB  - OBJECTIVE: Ankylosing spondylitis is a progressive, debilitating disease in which
      early diagnosis and early treatment can improve the prognosis. Radiographic
      confirmation is essential for diagnosis but conventional radiography has not
      proved useful, particularly in the early course of the disease. The aims of this
      study were to correlate the findings at conventional radiography with those at
      CT, and to correlate the duration of clinical symptoms with the radiological
      findings. MATERIAL AND METHODS: Forty patients with clinical sacro-iliitis and 13
      controls were evaluated by means of conventional radiography and CT. RESULTS:
      Conventional radiography was positive in 10/40 patients and CT in 30/40 patients.
      Conventional radiography was positive in only 2/14 patients with a symptom
      duration of less than 2 years while CT was positive in 10/14 such patients.
      CONCLUSION: The study demonstrated a considerably higher sensitivity in CT than
      in conventional radiography in detecting the subtle changes necessary for the
      radiological diagnosis of sacro-iliitis, particularly in cases of short duration.
      CT allows an early start to be made in treatment with a consequently improved
      prognosis. The use of conventional radiography cannot be recommended because its
      low sensitivity delays diagnosis in many instances.

PMID- 9571941
TI  - Tumoral calcium pyrophosphate dihydrate deposition disease with bone destruction
      in the shoulder. CT and MR findings in two cases.
AB  - We report on specific CT and MR features in two cases of tumoral calcium
      pyrophosphate dihydrate deposition disease in the shoulder with unusually large
      tumors. CT revealed features that were specific to the disease. MR was useful for
      detecting the extent of the mass and for obtaining information on adjacent soft
      tissue and bone-marrow changes.

PMID- 9571942
TI  - MR imaging in shoulder trauma. Value of STIR images.
AB  - PURPOSE: To determine the adequacy of MR standard protocols by analyzing
      conventional T1- and T2-weighted SE sequences, and to evaluate the usefulness of
      additional fat-suppressed (STIR) images in shoulder trauma. MATERIAL AND METHODS:
      Paracoronal T1-weighted, T2-weighted, SE, and STIR images were obtained on a 0.5
      T superconductive system in 25 patients with shoulder trauma. In a separate
      evaluation of T1/T2 images and a combined evaluation of T1/T2 SE- and STIR
      images, we compared the number of patients with evidence of Hill-Sachs lesions,
      bone bruises, and/or rotator-cuff lesions. RESULTS: Compared to the combined
      evaluation of T1/T2 and STIR images, the separate evaluation of T1/T2 SE images
      revealed identical results for rotator-cuff lesions and Hill-Sachs lesions, but
      different results for the bone bruises in the area of the major tubercle.
      CONCLUSION: Occult fractures of the major tubercle, indicated by areas of bone
      bruising, might be missed with MR using conventional SE images. We recommend the
      use of additional paracoronal fat-suppressed sequences in patients with
      clinically suspected lesions and equivocal findings on plain radiographs and on
      standard SE sequences.

PMID- 9571943
TI  - MR findings in tibial adamantinoma. A case report.
AB  - Adamantinoma of the long bones is a rare skeletal tumor and its MR features have
      seldom been reported. It is difficult to distinguish from other bone lesions
      (such as osteofibrous dysplasia or osteosarcoma) by means of conventional
      radiography and CT. MR imaging, however, may be useful in differentiating
      adamantinoma from such lesions. With this presentation of a typical case, we hope
      to draw the attention of radiologists to this lesion and contribute information
      on its MR appearance.

PMID- 9571944
TI  - Contrast-enhanced MR imaging as a prognostic indicator of breast cancer.
AB  - BACKGROUND: Using contrast-enhanced MR imaging in the diagnosis of breast cancer
      may provide additional information not only on tumor extension but also on the
      biological behavior of tumors. Thus certain characteristics such as tumor
      angiogenesis and the proliferating activity of the tumor, which have been shown
      to correlate significantly with prognosis, are both potentially amenable to
      analysis by MR imaging. MATERIAL AND METHODS: We compared contrast enhancement in
      50 malignant breast tumors at MR imaging to several prognostic factors, such as
      tumor size, lymph-node status, histological grade of malignancy, tumor
      angiogenesis, and proliferating activity as shown by the mitotic count and PCNA
      immunoreactivity. RESULTS: There was significant correlation between contrast
      enhancement at MR imaging of breast cancer and both tumor angiogenesis and
      proliferative cellular activity as shown by PCNA immunoreactivity. Furthermore,
      there was a correlation between contrast enhancement and tumor malignancy grade
      as well as tumor invasiveness. CONCLUSION: These observations suggest that
      contrast enhancement at MR imaging may be influenced by factors that have
      prognostic value. If this assumption is correct, contrast-enhanced MR imaging may
      become a valuable prognostic tool in the pre-operative evaluation of breast
      cancers.

PMID- 9571945
TI  - Ultrasonography of invasive lobular breast carcinoma.
AB  - PURPOSE: To review the US findings in invasive lobular breast carcinoma which is
      often difficult to diagnose clinically and mammographically. MATERIAL AND
      METHODS: The mammographic and US findings in 63 cases of pure invasive lobular
      carcinoma diagnosed at our institution in 1990-1996 were reviewed
      retrospectively. The US findings were classified as positive, negative or
      indeterminate for malignancy. RESULTS: Forty-nine of the 63 lobular carcinomas
      (78%, 95% CI 65.5-87.3%) were US-positive, and 51 (81%, CI 95% 69.1-89.8%) were
      mammography-positive. The US visibility of the carcinomas was affected by their
      palpability and mammographic appearance, and the radiographic density of the
      breasts. Indeterminate US findings (architectural distortion with acoustic
      shadowing) were visualized in 4 of the 10 cases that had asymmetric densities at
      mammography. CONCLUSION: The sensitivity of US for lobular carcinoma was not
      statistically different from that of mammography. The methods were complementary,
      especially with regard to evaluating dense breasts and lesions which were
      difficult to assess clinically and mammographically.

PMID- 9571946
TI  - Ultrasonography as a guidance method in the evaluation of mammographically
      detected nonpalpable breast lesions of suspected malignancy.
AB  - PURPOSE: To evaluate the role of ultrasonography (US) as a method of guidance for
      fine-needle aspiration biopsy or preoperative wire localization in the
      demonstration of nonpalpable mammographically detected breast lesions. MATERIAL
      AND METHODS: A total of 168 nonpalpable mammographically detected breast lesions
      were examined by means of high-resolution real-time US. RESULTS: US depicted: 55%
      of all the lesions (92/168); 88% of the circumscribed densities (45/51); 80% of
      the stellate densities (35/44); 47% of the asymmetric densities (7/15); and 9% of
      the microcalcifications (5/58). CONCLUSION: US was useful in guiding needle
      biopsy or wire localization in most of the circumscribed and stellate breast
      lesions, even in fatty breasts. However, with the equipment that is currently
      available, US was of no value in localizing microcalcifications.

PMID- 9571947
TI  - Sedation versus general anaesthesia in paediatric patients undergoing chest CT.
AB  - OBJECTIVE: CT of the chest in paediatric patients often requires sedation or
      general anaesthesia to minimize motion artefacts. Both sedation and general
      anaesthesia are associated with atelectasis which obscures the underlying
      pulmonary pathology. We conducted a prospective study to compare these two
      methods with respect to degree of motion artefacts and extent of atelectasis.
      MATERIAL AND METHODS: Nineteen patients undergoing 22 chest CT examinations were
      randomly selected for either sedation or general anaesthesia. The total area of
      atelectasis and the degree of motion artefacts were measured. RESULTS: The mean
      percentage of atelectasis was 6.67% for general anaesthesia and 0.01% for
      sedation (p = 0.01). There was no significant difference in the quality of the
      images between the sedation patients and the general anaesthesia patients.
      CONCLUSION: Whenever the clinical condition permits it, sedation rather than
      general anaesthesia should be given to paediatric patients undergoing chest CT.

PMID- 9571948
TI  - MR imaging in a desmoid tumor of the posterior mediastinum with extension into
      the abdominal cavity. A case report.
AB  - We report on a rare case of desmoid tumor in a 40-year-old man with low back pain
      and cough. There was no history of previous surgery or trauma. MR imaging
      revealed a posterior mediastinal mass extending into the abdominal cavity.

PMID- 9571949
TI  - Hepatic parenchymal perfusion abnormalities after pancreaticobiliary surgery.
      Evaluation with dynamic helical CT.
AB  - PURPOSE: To evaluate perfusion abnormalities of the liver after
      pancreaticobiliary surgery. MATERIAL AND METHODS: We retrospectively evaluated
      128 patients with pancreaticobiliary malignant tumors who had been examined both
      before and after surgery by means of helical CT of the liver. An infusion of 3
      ml/s of 60% nonionic contrast material was followed by helical CT of the liver in
      a sequential arterial phase, portal venous phase, and equilibrium phase. RESULTS:
      Of 128 patients, we followed 97. In 21 patients (22%) we found 47 lesions with
      perfusion abnormalities that were detected 1-33 months (mean 6.6 months) after
      the operation. All patients were asymptomatic. The shape of each perfusion
      abnormality was characterized as geographic (n = 23, 47%), wedge-shaped (n = 21,
      45%), or round (n = 3, 8%). The abnormalities were seen in the arterial phase in
      46 lesions (98%), in the portal venous phase in 18 lesions (38%), and in the
      equilibrium phase in 1 lesion (0.2%). In all lesions, the size either decreased
      spontaneously, or it remained unchanged for more than one year. CONCLUSION:
      Perfusion abnormalities of the liver may occur in patients who undergo
      pancreaticobiliary surgery. This findings should not be confused with
      hypervascular metastases.

PMID- 9571950
TI  - Relationship of 31P MR spectroscopy to the histopathological grading of chronic
      hepatitis and response to therapy.
AB  - PURPOSE: In vivo phosphorus-31 MR spectroscopy (31P MRS) was performed in the
      human liver in order to investigate the relation between: the ratios of
      phosphorus metabolites in the liver; the histopathological grading of chronic
      hepatitis; and the response to therapy. MATERIAL AND METHODS: Hepatic 31P MRS
      using the DRESS method (depth-resolved surface-coil spectroscopy) was carried out
      in 45 patients with chronic viral hepatitis or autoimmune hepatitis, and in 16
      control subjects. We measured the ratios of the peak areas of phosphomonoesters
      (PME), inorganic phosphate (Pi), or phosphodiesters (PDE) to the peak area of
      beta-adenosine triphosphate (ATP). RESULTS: The PDE/ATP ratio of patients with
      chronic hepatitis or liver cirrhosis was lower than that of control subjects
      (liver cirrhosis = 0.74; chronic active hepatitis = 1.13-1.21; normal = 1.43);
      only a small difference was found in the PME/ATP and Pi/ATP ratios. There was no
      correlation between the spectra and histopathological grading or response to
      therapy, but the response to therapy was poor when a reduced PDE/ATP ratio was
      present. CONCLUSION: The PDE/ATP ratio measured by 31P MRS makes it possible to
      identify the transition of chronic active hepatitis into liver cirrhosis with a
      poor response to therapy.

PMID- 9571951
TI  - Diagnosis of acute left-sided colonic diverticulitis by three radiological
      modalities.
AB  - PURPOSE: To compare the findings at US, CT and contrast enema (CE) with the
      clinical, biochemical, and surgical findings in patients with suspected acute
      left-sided colonic diverticulitis (ALCD). MATERIAL AND METHODS: The study
      comprised 32 consecutive patients hospitalized with clinically diagnosed ALCD.
      During the first 3 days of hospitalization, they were examined by US and CT of
      the pelvis and abdomen, and CE. RESULTS: Of the 32 patients, 21 had ALCD
      according to the combined radiological, clinical, biochemical and surgical
      findings. Findings compatible with ALCD were verified by radiological examination
      alone in 12 patients (4 patients at US, 10 at CT, and 6 at CE). In 9 patients,
      only diverticula or tethering was found at either CE or CT, and the diagnoses
      were then supported by clinical and biochemical findings and clinical follow-up.
      The most common clinical symptoms and signs associated with ALCD were left lower
      quadrant pain, left-sided tenderness, and fever. Most patients showed elevations
      of the white blood-cell count, erythrocyte sedimentation rate, and C-reactive
      protein, but there was no statistical difference in the stages of severity of
      ALCD, or between ALCD and other abdominal disorders. CONCLUSION: Radiological
      examination is valuable in confirming the diagnosis of ALCD. CT was the
      radiological modality that best demonstrated ALCD and revealed complications
      (e.g. pericolic abscesses) during the course of the illness.

PMID- 9571952
TI  - Carcinoma of the uterine cervix. High-resolution turbo spin-echo MR imaging with
      contrast-enhanced dynamic scanning and T2-weighting.
AB  - PURPOSE: To compare high-resolution contrast-enhanced (Gd-DTPA) dynamic MR
      imaging with T2-weighted turbo spin-echo (TSE) imaging in the evaluation of
      uterine cervical carcinoma. MATERIAL AND METHODS: Thirty-two patients with
      cervical carcinoma underwent MR imaging on a 1.5 T superconductive unit to have
      the extension of the disease assessed before treatment. A phased-array coil was
      used in all patients. In 25 patients, surgical confirmation of the diagnosis was
      obtained after imaging. Radiation therapy was selected for the remaining 7
      patients with advanced carcinoma. Qualitative and quantitative image analyses
      were also performed. RESULTS: The cervical carcinomas showed maximum contrast in
      the cervical stroma and myometrium in the early dynamic phase. The tumor/cervical
      stroma contrast in the early dynamic phase obtained with the T1-weighted TSE
      technique (contrast-to-noise ratio 22.6) was significantly higher than that
      obtained in T2-weighted TSE imaging (contrast-to-noise ratio 4.3). In the
      evaluation of parametrial invasion, the accuracy of T2-weighted imaging was 71.8%
      and contrast-enhanced dynamic imaging 81.2%. CONCLUSION: High-resolution contrast
      enhanced (Gd-DTPA) dynamic MR imaging in cervical cancer offers improved
      tumor/cervical-stroma contrast and provides useful information on parametrial
      invasion.

PMID- 9571953
TI  - Krukenberg tumor findings at color and power Doppler US; correlation with
      findings at CT, MR imaging, and pathology. Case reports.
AB  - We report on the findings at color and power Doppler US in 2 cases of Krukenberg
      tumor. Power Doppler US may suggest a Krukenberg tumor when it shows a relatively
      prominent vascular signal along the wall of well-demarcated intramural cysts in a
      solid ovarian mass.

PMID- 9571954
TI  - CT in spontaneous adrenal gland rupture. A case report.
AB  - PURPOSE: To report on an exceptional case of spontaneous, idiopathic, unilateral
      adrenal gland rupture that caused massive retroperitoneal hemorrhage. METHODS AND
      RESULTS: US and CT were performed in a patient who presented with acute abdominal
      pain. Urgent adrenalectomy was required to prevent the blood loss from
      continuing. The CT findings were correlated with the histological findings.
      CONCLUSION: CT proved to be an accurate imaging modality by which to diagnose
      adrenal hemorrhage. The absence of irregular tissue enhancement showed that
      neoplasia was not the underlying cause of the hematoma.

PMID- 9571955
TI  - Film processing and the environment. Reducing pollution, water consumption, and
      costs.
AB  - PURPOSE: X-ray film processing is associated with pollution from photo chemicals
      and from the water used to rinse the film. We tested a new processing system that
      was aimed at reducing both environmental pollution and costs through the use of
      solid photo chemicals and recirculation of the rinsing water. MATERIAL AND
      METHODS: Before and after the installation of new mixers for the solid chemicals
      and a system for recirculating the rinsing water, we measured: water consumption,
      processor function quality, image quality, archivability, and the waste-silver
      content in the rinsing water. RESULTS: After the installation of a simple system
      for recirculating the rinsing water, there was an 88% reduction in water and film
      consumption as shown in the amount of water/m2 film that was used. At the same
      time, the release of silver-contaminated rinsing water directly into the sewers
      was stopped. Image quality remained unchanged. Archivability was assessed at more
      than 100 years. The solid photo chemicals and specially designed mixers proved
      efficient and provided a stable image quality of high standard. It was thus
      possible to reduce the risk of pollution from the transportation, storage and
      handling of liquid chemicals. CONCLUSION: A simple recirculation system for the
      rinsing water would significantly reduce water consumption and eliminate
      contamination of the environment by silver. The on-site preparation of photo
      chemicals proved viable and reduced the costs of film processing.

PMID- 9571957
TI  - British Society for Rheumatology XVth annual general meeting joint with the
      Spanish Society for Rheumatology and the British Health Professionals in
      Rheumatology Spring Meeting. Brighton, United Kingdom, 22-24 April 1998.
      Abstracts.

PMID- 9571956
TI  - Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver
      and pancreas.
AB  - Contrast-enhanced magnetic resonance imaging (MRI) of the liver and pancreas is
      frequently performed to improve the sensitivity and specificity of lesion
      detection in these organs. The concept of using tissue-specific contrast media is
      to selectively enhance the normal parenchyma, but not lesions, so that the
      contrast between tumorous and normal tissue is increased, and lesion
      detectability improved. Mangafodipir trisodium (MnDPDP) has been developed as a
      hepatocellular-specific contrast agent, but uptake has also been found in
      pancreatic tissue. In this study the safety and diagnostic efficacy of MnDPDP
      were investigated in both healthy volunteers and in patients with liver and
      pancreatic tumors. In healthy volunteers (n = 8), dose-dependent enhancement in
      T1-weighted images was observed in the normal liver and pancreatic parenchyma
      after infusion of MnDPDP at doses of 5 and 10 mumol/kg. The maximal enhancement
      in the two dose groups was 77 and 110% in the liver, and 57 and 84% in the
      pancreas, respectively. The enhancement-over-time profiles demonstrated that the
      effective imaging window was about 2 h for the liver, and over 4 h for the
      pancreas. There was no measurable enhancement in brain structures protected by
      intact blood-brain barrier, and no changes of clinical importance were found in
      vital signs or in blood and urinary chemistry variables. Compared with unenhanced
      images (including T2-weighted images), significantly more lesions were detected
      on MnDPDP-enhanced T1 images in 82 patients with liver tumors (mostly
      metastases). Features such as rim enhancement and the enhancement in
      hepatocellular carcinomas can provide information for differential diagnosis. In
      a study on patients with pancreatic tumors, mainly adenocarcinomas (n = 21) and
      islet cell tumors (n = 19), two additional lesions were found in the MnDPDP
      enhanced images. The contrast enhancement in the pancreatic parenchyma can vary
      greatly, depending on the site of the enhancing part of the organ in relation to
      a large tumor. The tumors of both origins were also enhanced post-contrast, but
      to a lesser degree than the normal pancreatic tissue. MnDPDP enhancement was
      investigated in 30 liver metastases from endocrine tumors in 13 patients. These
      lesions showed a signal increase of about 49% post-contrast, which lasted longer
      than that in the normal liver tissue. The findings may help to distinguish these
      tumors from other metastatic tumors. T1-weighted sequences of four types,
      including a spin-echo and three variants of fast gradient-echo sequences, and
      various parameter combinations, were investigated in healthy volunteers (n = 6),
      with the aim of finding the optimal sequence for MnDPDP-enhanced MRI of the liver
      and pancreas. The fat-and-water out-of-phase, fast field (gradient)-echo sequence
      was the best for imaging of both the liver and pancreas. The studies have shown
      that MnDPDP is safe when given as an infusion, and is effective as a liver- and
      pancreas-specific contrast medium, with improved lesion detection in MRI of these
      organs. It is also useful for the characterization of liver tumors.

PMID- 9571958
TI  - Orthopaedic proceedings, 1996-1997.

PMID- 9571959
TI  - 8th International ANCA Workshop. Birmingham, United Kingdom, 2-5 April 1998.
      Abstracts.

PMID- 9571960
TI  - [Hormone tolerance mechanism of prostate cancer].
AB  - One of the delicate problems in a cancer treatment is the acquisition of a
      tolerance for a medicine. Antiandrogen treatment is valid in treatment of
      prostate cancer, but the disease develops into hormone-refractory prostate cancer
      after a uniformity period. The molecular mechanisms of recurrence and endocrine
      therapy failure in prostate cancer have remained unclear. In this paper we
      discuss the hormone-refractory prostate cancer that has been reported by many
      investigators.

PMID- 9571961
TI  - [Introduction of new GCP (good clinical practice)].
AB  - In 1997, a new GCP has taken effect by the Ministry of Health and Welfare, Japan,
      and will be enforced as of April, 1998. The GCP regulates the method of clinical
      trials in the light of ethics and science. The New GCP requires written informed
      consent, enforcement of the responsibility of the client and so on.

PMID- 9571962
TI  - [New Japanese GCP--from the standpoint of a sponsor].
AB  - The new Japanese GCP enacted on the basis of ICH-GCP adopts more clear concepts
      of quality assurance for a clinical trial. This article briefly describes its
      principles. Sponsors are now responsible not only for initiation but also for
      management of clinical trials. Thus, discussions have been under taken the points
      to be considered in, among others, imple mentation/maintenance of the Quality
      Assurance/ Control systems, preparation/amendment of a clinical trial protocol,
      entrusting to a coordinating investigator/committee, monitoring, audit, and
      direct access to source documents and all other trial-related records. Further,
      this addresses the required reorganization which the sponsor should strive for as
      well as the sponsor's requests to participating medical institutions such as
      adoption of a "study coordinator". To improve the quality of a clinical trial, it
      would be necessary to refer not only to GCP but also to other current guidelines
      such as those harmonized at the ICH.

PMID- 9571963
TI  - [Development of anti-cancer drugs under new renewed GCP--from the viewpoint of
      drug development company developer].
AB  - During the past 7 years since the enforcement of Japan's first GCP in October
      1990, various standards and guidelines have been introduced in Japan. On the
      other hand, the harmonization of GCP has been the subject of major discussion at
      ICH in order to allow the mutual acceptance of clinical data from different
      countries. In order to further improve the reliability and consistency of
      clinical data and the ethics of clinical trials in Japan, the new GCP was
      enforced in April 1997. A clinical study is conducted by the sponsor, but will
      only be successful with the collaboration of trial subjects, medical
      institutions, heads of medical institutions, investigators, subinvestigators,
      pharmacists, nurses, laboratory technicians, and other assisting staff. Before
      the full enforcement of the new GCP, we, as sponsors of clinical trials, carried
      out a survey of the current status of clinical trials centering on the reactions
      of medical institutions to the new GCP, future of clinical trials on anti-cancer
      drugs in Japan, and differences in time from clinical trials to registration in
      Japan, the United State and Europe. We sent a questionnaire by facsimile to 21
      pharmaceutical companies which have developed or are developing anti-cancer drugs
      and obtained replies from 20 companies (95%) from August 25 to 30, 1997. This
      paper reports issues concerning clinical trials on anti-cancer drugs based on the
      results of our survey.

PMID- 9571964
TI  - [Essential conditions for the development of new anticancer drugs based on ICH
      GCP].

PMID- 9571965
TI  - [Influence of new Japanese GCP on pharmaceutical-company-directed clinical trials
      and physician-directed clinical studies in the surgical field].
AB  - The Japanese Ministry of Health and Welfare issued a revised version of Good
      Clinical Practice (GCP) in 1997 which regulates the method and procedure of new
      drug development. The largest issue is the discrepancy between the present status
      of drug development system and requirements by new GCP. Characteristics of phase
      III study in the surgical field requires a large number of accrued patients,
      takes long observation time, and much money to achieve. The study needs well
      trained doctors, nurses, study coordinators, a data manager, and statisticians.
      However, conventional study has largely depended on doctors who might not be able
      to respond to all requirements without the cooperation of other paramedical
      staff. Pharmaceutical companies could afford in a few months to organize a new
      drug development system to meet the requirements of the new GCP. However,
      physician-directed clinical study has insufficient financial support to realize
      data assurance of high quality. Because the development of actual treatment
      depends on the results of physician-directed clinical study, a high-level
      research organization such as in the western countries should be urgently
      established, and the fruits of the study should be reflected in government policy
      in the health assurance system.

PMID- 9571966
TI  - [Preoperative chemotherapy for advanced colorectal carcinomas--comparison of
      histological effect between UFT + leucovorin tablet and UFT alone].
AB  - The authors analyzed the histological effect of preoperative chemotherapy for 41
      colorectal advanced cancer patients using resected specimens. Twenty patients in
      the UFT + LV group received 400 mg/day of UFT and 30 mg/day of leucovorin for 10
      14 days just before the operations. Twenty-one patients with UFT alone received
      UFT 400 mg/day during the same period. Only one patient in the UFT + LV group
      developed the side effect of mild leukocytopenia. The histological effect of the
      UFT + LV group was superior to that of the UFT alone group (p = 0.03). The number
      of Grade 1a and 1b in the UFT + LV group was 14 (60.9%) and 7 (30.4%), while in
      the UFT group 16 (66.7%) and 2 (8.3%). Histological examination revealed no
      lesions which showed Grade 2 and 3 in both groups. There was the tendency for the
      histological effect in moderately differentiated adenocarcinomas to be superior
      to that in well-differentiated adenocarcinomas in both group. The histological
      effect in metastatic lymph nodes was superior to that in the original colorectal
      lesions in both groups. This suggests preoperative chemotherapy with UFT + LV and
      UFT could achieve the clinical down-staging of advanced colorectal cancer.

PMID- 9571967
TI  - [Continuous intraportal chemotherapy for prevention of metachronous hepatic
      metastasis in colorectal cancer].
AB  - Fifty-five colorectal cancer patients who had continuous intraportal chemotherapy
      between 1990 and 1993 (treated group) and 130 colorectal cancer patients who did
      not have portal chemotherapy between 1982 and 1993 (untreated group) were studied
      to clarify the effects of continuous intraportal chemotherapy on the prognosis.
      After a catheter was placed in the portal vein through the right gastroepiploic
      vein at the time of radical operation, 10 mg of MMC was continuously infused for
      4 hours at operation and 500 mg/day of 5-FU was continuously infused for 7 days
      postoperatively. The toxicities of this therapy were not serious. The five-year
      survival rate was 65.3% in the treated group and 65.6% in the untreated group.
      The five-year disease-free survival rate was 69.8% in the treated group and 58.6%
      in the untreated group, with no significant difference. In stage II patients,
      however, the five-year disease-free survival rate in the treated group was
      slightly higher than in the untreated group (90.0% vs 70.3%, p = 0.073), and the
      rate of hepatic recurrence in the treated group was significantly lower than in
      the untreated group. These results suggest that continuous intraportal
      chemotherapy may prevent metachronous hepatic metastases in stage II colorectal
      cancer patients.

PMID- 9571968
TI  - [Effect of 5'-DFUR used concurrently in radiotherapy and immunotherapy uterine
      cervical cancer--pilot study. Study of 5'-DFUR for Uterine Cervical Cancer].
AB  - We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose
      dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR
      and SPG for patients with uterine cervical cancer, which was regarded as suitable
      for cases of radiotherapy. The patients were randomly allocated into group A (5'
      DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent
      radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg
      twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or
      IV a with histologically diagnosed primary squamous cell carcinoma of uterine
      cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy
      evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%
      97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety
      evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No
      significant difference in efficacy and safety was observed between the two
      treatment groups. These results suggested that the combination therapy of
      radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness
      must be confirmed for advanced squamous cell carcinoma of uterine cervix. To
      confirm dose dependency of 5'-DFUR, it seems further consideration with more
      patients is needed.

PMID- 9571969
TI  - [A clinical phase III trial of MR-20 in gynecologic nephrotoxicity of cisplatin-
      a comparative study in MR-20-treated and control patients on cyclical
      intermittent cisplatin treatment].
AB  - MR-20 was administered to 52 gynecological cancer patients who presented with
      nephrotoxicity from cisplatin (CDDP) treatment over 3 courses at 33 institutions
      throughout Japan during the period from July 1992 through March 1994, in order to
      study its suppressive effect on the nephrotoxicity as well as its safety; and the
      results are reported in this paper. METHODS: The efficacy and usefulness of MR-20
      were studied by a MR-20-untreated-controlled, non-double-blind manner. An
      efficacy rate of 72.0% was achieved in the MR-20 group, and 37.0% in the
      untreated group: MR-20 was significantly more effective for nephrotoxicity than
      the MR-20-untreated group. Ccr was prevented from significant variations in the
      MR-20 group, compared with the untreated group. It was considered that MR-20 is a
      safe drug, and that it is useful in suppressing the nephrotoxicity of CDDP
      treatment.

PMID- 9571970
TI  - [Clinical study on the inhibitory effect of a 5-HT3 antagonist, granisetron, for
      nausea and vomiting induced by chemotherapy (CHOP, VEPA, high-dose ETP) for non
      Hodgkin's lymphoma].
AB  - The antiemetic effect of granisetron on nausea and vomiting induced by cancer
      chemotherapy (CHOP, VEPA, VEPA-B, massive dose of ETP) was studied in fifty
      patients with non-Hodgkin's lymphoma. There was almost no difference in the
      inhibitory effect by regimen, with the rates of perfect inhibition of nausea and
      vomiting standing at 55.6% to 60%. Nausea and vomiting was perfectly controlled
      in 60% of 35 patients receiving CHOP therapy. As a part of this study, a
      comparison was made of perfect inhibitory effect on nausea and vomiting by
      potency of chemotherapy under the potency scale of 750 mg/m2 of CPA as 1,
      revealing no significant difference in the rates of complete inhibition as 71.4%
      for a drug potency of less than 0.8 vs 52.4% for 0.8 or above (p = 0.26).
      However, it was clear that the higher the dose of chemotherapy, the lower the
      rate of complete inhibition. The results confirmed the high efficacy and safety
      of granisetron in the treatment of nausea and vomiting induced by cancer
      chemotherapy.

PMID- 9571971
TI  - [Evaluation of a new anti-cancer drug regimen for surface epithelial-stromal
      ovarian cancer].
AB  - BACKGROUND: The purpose of this study was to describe a new anti-cancer drug
      regimen for epithelial ovarian cancer. METHODS: The cytotoxicities of some anti
      cancer drugs regimens against human epithelial ovarian cancer xenografted into
      nude mice (TOM, TOH, TON) have been studied. The activities of CDDP, CPT-11, TXL,
      CDDP + CPM, CDDP + CPT-11, CDDP + TXL, CPT-11 + CPM, CPT-11 + TXL, and TXL + CPM
      were evaluated comparing with a control group using saline. Three mice were used
      for each group, and when the xenografted tumor reached 6 mm in diameter, 1/5 LD50
      of these drugs was administered into the peritoneal cavity of mice once a week
      for three weeks. RESULTS: The three most effective regimens were CPT-11 + TXL,
      CDDP + CPM, and CDDP + CPT-11 for epithelial ovarian cancer.

PMID- 9571972
TI  - [A case report of neoadjuvant intra-arterial injection chemotherapy combined with
      peripheral blood stem cell reinfusion in an advanced breast cancer patient].
AB  - A seventy-one year-old woman suffered from Stage IIIb advanced breast cancer
      complicated with direct thoracic invasion and skin eruption. An indwelling intra
      arterial catheter was inserted into the subclavian artery for the administration
      of anti tumor agents. After three courses of neoadjuvant chemotherapy combined
      with G-CSF and/or PBSCT reinfusion, the breast cancer revealed a remarkable size
      reduction and was absent from direct thoracic and pectoral muscle, invasion
      within the physical status and visual analysis by CT scan. Thereafter, the
      patient underwent a radical mastectomy. In the pathological findings of the
      operation specimen, despite a remarkable tumor collapse, the microscopic invasion
      remained in the shallow layer of the pectoral muscle. Thus, the patient should be
      given additional postoperative irradiation. The patients has had six months of
      stable tumor-free survival since the mastectomy.

PMID- 9571973
TI  - [A case report of advanced breast cancer with remarkable response to
      chemoendocrine therapy (CTF + MPA)].
AB  - A 59-year-old female complaining of breast tumor with suppurative discharge was
      diagnosed as having advanced breast cancer (T4cN3M1-StIV), with giant liver
      metastasis. Seven courses of combined chemoendocrine therapy (CTF + MPA) were
      used. Following the chemoendocrine therapy, primary tumor, lung, pleural,
      supraclavicular and parasternal metastasis disappeared, and the liver metastasis
      was obviously diminished. These effects continued for 1 year 7 months. Although
      CTF + MPA chemoendocrine therapy is widely used with advanced or recurrent breast
      cancer, a clearly effective case has almost never been reported. The reason for
      the remarkable effect in this case was the consistent immunity to breast cancer.

PMID- 9571974
TI  - [Breast cancer with liver metastasis responsive to docetaxel: case report].
AB  - A 59-year-old female underwent mastectomy for right breast cancer in November
      1992. She received tamoxifen and anthracycline-containing chemotherapy as
      adjuvant therapy. In and after September 1994, she developed loco-regional
      recurrences five times in total, each of which was treated with surgery and
      conventional combination chemotherapy. In April 1997, she developed liver
      metastasis, which was refractory to biochemical modulation therapy (low-dose
      cisplatin + 5-FU). We, therefore, treated her six times with docetaxel 80 mg,
      which resulted in partial response of the liver metastasis and brought about a
      marked decrease in serum CA15-3 levels. Adverse effects of docetaxel were grade 3
      alopecia and leucocytopenia. She has been well without re-growth of the liver
      metastasis for over five months.

PMID- 9571975
TI  - [A case of advanced hepatocellular carcinoma responding to suppository of
      Tegafur].
AB  - We report a case of advanced hepatocellular carcinoma (HCC) successfully
      controlled by the suppository administration of Tegafur alone. Five months after
      initiation of the drug, excellent reduction of tumors and decrease of serum alpha
      feto-protein (AFP) level were seen without any side effects. Also, twenty-four
      months after of the treatment, no regrowth of tumors or increase in the serum AFP
      level was seen. Because Tegafur is a time-dependent agent, advanced HCC may be
      controlled by continuous administration for a long period.

PMID- 9571976
TI  - [Percutaneous ethanol and acetic acid injection for liver metastasis from colon
      cancer--two case reports].
AB  - Two cases of liver metastasis from colon cancer were treated by percutaneous
      ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after
      surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial
      hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year
      later, recurrence of liver tumor was detected, and PEI and PAI were performed for
      the metastatic lesions of the liver. Tumor regression and histopathological
      examination revealed coagulative necrosis. The patient died of lung metastasis 2
      years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending
      colon cancer and liver metastasis, who received surgery, and chemotherapy with
      intraarterial 5-FU infusion was continued. Four months later, recurrence of liver
      metastasis with elevation of serum CEA was noted. The patient received PEI three
      times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis
      at the site of PEI. The patient has been alive for 1 year and 6 months with a new
      recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem
      to be useful for the treatment of unresectable liver metastasis.

PMID- 9571977
TI  - [Syndrome of inappropriate secretion of antidiuretic hormone and neurotoxicity
      induced by vincristine and alkylating agents during chemotherapy for malignant
      lymphoma of thyroid gland].
AB  - We report a syndrome of inappropriate secretion of antidiuretic hormone (SIADH),
      neurotoxicity and facial erythema induced by several anti-cancer drugs in a case
      of malignant lymphoma of thyroid gland. A 68-year-old male was admitted,
      complaining of neck tumor and dyspnea. On admission, he was treated with
      vincristine (VCR) for bronchostenosis due to malignant lymphoma. Neck tumor and
      mediastinal lymph node swelling reduced. On the ninth day after chemotherapy of
      VCR, a consciousness disturbance was found and he was diagnosed as having SIADH.
      Following chemotherapy of cyclophosphamide, SIADH was also induced so he was
      treated with irradiation for neck and mediastinal field, instead of chemotherapy.
      During irradiation, however, enlargement of systemic lymph nodes appeared, and
      the chemotherapy was resumed. He achieved partial remission, but somnolence after
      ifosfamide and facial erythema after ranimustine were observed. In spite of the
      difference in the chemical structure of these anti-cancer drugs, several side
      effects occurred. It is suggested that the direct effects of drugs on the nervous
      system were SIADH and neurotoxicity.

PMID- 9571978
TI  - [Pilot study of cisplatin, ifosfamide and irinotecan (CPT-11) with granulocyte
      colony-stimulating factor support (CIC-regimen) in relapsed small-cell lung
      cancer].

PMID- 9571979
TI  - [TNM classification of gynecological tumors].
AB  - Gynecological tumors of cervix uteri, corpus uteri, ovary, vagina, and vulva are
      classified by the TNM systems. The definitions of the T categories correspond to
      several stages accepted by FIGO (Federation Internationale de Gynecologie et
      d'Obstetrique). Those of regional lymph nodes are different among primary sites.
      The relationships between 5-year survival rates and TNM stages were investigated
      in cervical and endometrial carcinoma cases in 1985 by the Japan Society of
      Obstetrics and Gynecology (JSOG). The pTNM pathological classification had a
      better relationship with survival than the TNM clinical classification,
      respectively. According to the rules for TNM classification, T categories should
      be assessed by physical examination, cytoscopy and urography. These data indicate
      that prognostic factors could not be accurately assessed by these procedures.
      Radiotherapy for cervical carcinoma is selected in many cases. The JSOG adopts
      the clinical classification in 1997, but it had a pathological classification for
      corpus uteri and ovary in 1995.

PMID- 9571980
TI  - Relationship between psychotropic drugs and thyroid function: a review.
AB  - Some widely used psychoactive drugs, such as tricyclic antidepressants and
      antipsychotic phenothiazines exhibit iatrogenic effects on the thyroid. These
      side effects may arise from interactions at different steps of thyroid hormone
      biosynthesis. These drugs can induce a change in iodine capture by thyroid cells
      or can complex iodine, making it unavailable for thyroid hormone synthesis and
      thus decreasing thyroid hormone blood levels; they can also inhibit thyroid
      peroxidase activity and thus T3 and T4 synthesis or enhance deiodination of T4 to
      T3 or to Rt3 by stimulation of deiodinase activity. Moreover, tricyclic
      antidepressants interfere with the hypothalamic-pituitary-thyroid axis via the
      noradrenergic or serotonergic systems and might therefore decrease T4 or T3 blood
      levels, respectively. Phenothiazines can induce autoimmune hypothyroidism, as
      shown by an increase in the expression of the major histocompatibility complex
      antigen and by a production of antithyroglobulin or antithyroperoxidase
      antibodies. However, all these mechanisms are only speculative in humans, as they
      have only been demonstrated in vitro or in animal experiments. Clinically,
      thyroid function and affective disorders are closely linked. On one hand, the
      therapeutic response to antidepressants could be influenced by the thyroid
      status; on the other hand, the larger the thyroxin decrease induced by
      antidepressants, the better the therapeutic effect might be. Moreover,
      cotreatment with thyroid hormones and antidepressant drugs could allow either a
      decrease in the rate of treatment failure or a faster recovery from depression.
      As antipsychotic or antidepressant treatments are administered over long periods
      in humans, their thyroid toxic effects must be taken seriously.

PMID- 9571981
TI  - Immunotoxicology of cigarette smoke condensates: suppression of macrophage
      responsiveness to interferon gamma.
AB  - We have investigated systematically the effects of short-term exposure to main
      stream cigarette smoke condensates (CSC-MS) on basal and inducible functional
      capacities of murine peritoneal exudate macrophages. Macrophages treated with CSC
      MS form granules that fluoresce orange under blue excitation, consistent with the
      speculation that they are polycyclic aromatic hydrocarbons (PAH). CSC-MS
      selectively suppressed interferon gamma (IFN gamma) induction of four macrophage
      functional capacities: enhanced phagocytosis of immunoglobulin-opsonized sheep
      red blood cells, TPA-induced H2O2 production, class II major histocompatibility
      complex expression, and nitric oxide synthesis. In contrast, two macrophage
      functions that are not induced by IFN gamma, basal electron transport and LPS
      induced TNF alpha production, were enhanced by treatment with CSC-MS. These
      results suggest that the suppressive effects of CSC-MS on macrophage
      responsiveness were selective and were not due to nonspecific inhibition of
      general functions such as RNA or protein synthesis. Since macrophage
      responsiveness to IFN gamma can result in induction of functional capacities that
      are fundamental to immunity, the data suggest that CSC-MS maybe deleterious to
      the general health of the smoker.

PMID- 9571982
TI  - Renal transport systems for organic anions and cations in cadmium-exposed rats.
AB  - To evaluate the effect of cadmium intoxication on renal transport systems for
      organic anions and cations, transport of p-aminohippurate (PAH) and
      tetraethylammonium (TEA) were studied in renal cortical plasma membrane vesicles
      isolated from cadmium-intoxicated rats. Cadmium intoxication was induced by daily
      injections of CdCl2 (2 mg Cd/kg.day sc) for 2-3 weeks. Renal plasma membrane
      vesicles were prepared by Percoll gradient centrifugation and magnesium
      precipitation method. Vesicular uptake of substrate was determined by rapid
      filtration technique using Millipore filter. The cadmium treatment resulted in a
      marked attenuation of Na(+)-dependent, alpha-ketoglutarate (alpha KG)-driven PAH
      uptake in the basolateral membrane vesicle (BLMV), and this was due to a
      reduction in Vmax and not K(m). The Na(+)-alpha KG symport activity of the BLMV
      was not affected by 2-week cadmium treatment, but it was significantly inhibited
      by 3-week cadmium treatment. On the other hand, the alpha KG-PAH antiport
      activity of the BLMV appeared to be markedly suppressed in 2-week as well as 3
      week cadmium-treated animals. The cadmium treatment inhibited the proton gradient
      dependent TEA transport in the brush-border membrane vesicle (BBMV), and this was
      associated with a reduction in Vmax with no change in K(m). These results
      indicate that cadmium exposures may impair the capacities for organic anion
      transport in the proximal tubular basolateral membrane and organic cation
      transport in the luminal membrane. The cadmium effect on organic anion transport
      is attributed mainly to an inhibition of dicarboxylate-organic anion antiport
      system.

PMID- 9571983
TI  - The effect of chlorine substitution on the dermal absorption of polychlorinated
      biphenyls.
AB  - The fate of selected mono-, di-, tetra-, and hexachlorobiphenyls was investigated
      following single dermal administration (0.4 mg/kg) to determine the effects of
      chlorine substitution on the dermal absorption and disposition of polychlorinated
      biphenyls (PCBs). Single dermal doses of 14C-labeled mono-, di-, tetra-, and
      hexachlorobiphenyls were administered to 1-cm2 areas on the backs of F-344 male
      rats. Unabsorbed radioactivity was removed from the dose site either at
      euthanasia or 48 h postdose. Distribution of radioactivity in the dose site and
      selected tissues was determined by serial sacrifice at time points up to 2 weeks.
      Dermal penetration varied inversely with degree of chlorination and at 48 h
      ranged from ca. 100% for monochlorobiphenyl to ca. 30% for the
      hexachlorobiphenyl. Penetration rate constants correlated well with log kow. PCBs
      were retained in the epidermis for up to 2 weeks postdose. The data from these
      studies suggest that systemic absorption of PCBs involves a combination of
      sequential processes including penetration across the stratum corneum, possibly
      metabolism in the epidermis and/or dermis, adsorption to proteins, and finally
      absorption into the systemic circulation. The skin favors the rapid absorption of
      less chlorinated PCBs, but the relatively rapid metabolism and elimination of
      these compounds would result in lower body burdens. More highly chlorinated PCBs
      penetrate less rapidly but remain in the site of exposure and slowly enter the
      systemic circulation. The dermal absorption of a commercial PCB mixture was
      modeled, and the results suggest that the net result of the differences in
      absorbance rates would be a greater body burden of higher chlorinated PCBs
      relative to those that have a lower chlorine content.

PMID- 9571984
TI  - Testicular toxicity of molinate in the rat: metabolic activation via
      sulfoxidation.
AB  - Molinate is a thiocarbamate herbicide widely used in rice culture. Studies
      conducted for regulatory purposes have indicated that molinate exposure causes
      male reproductive damage in rats. The present study describes the testicular
      lesion after administration of single doses of molinate. The hypothesis that a
      metabolite of molinate is responsible for testicular toxicity was also
      investigated. Testicular damage was evaluated histopathologically in Sprague
      Dawley rats 48 h and 1, 2, and 3 weeks after administration of molinate (100-400
      mg/kg i.p.). No testicular damage was seen at any time point at the 100 mg/kg
      dose level. Damage was first seen 1 week after 200 mg/kg and 48 h after 400
      mg/kg. The lesion was characterized by Sertoli cell vacuolation, failed
      spermiation, and phagocytosis of spermatids particularly evident at Stages X and
      XI. With increasing time, damage progressed until disorganization of the
      seminiferous epithelium was extensive, multinucleated giant cells were numerous,
      and neither spermatozoa nor late step spermatids were present. At 3 weeks after
      administration of the two higher-dose levels, germ cells in the seminiferous
      tubules were almost completely absent. Administration of the sulfoxide metabolite
      of molinate (200 mg/kg i.p.) caused testicular damage similar in severity to that
      seen at the 400 mg/kg dose level for the parent compound, indicating that it was
      more potent as a testicular toxicant. In vitro metabolism studies using liver and
      testis microsomes found that the major metabolite in both preparations was
      molinate sulfoxide. Testis microsomes produced only slightly less sulfoxide when
      compared with liver microsomes. Molinate was also metabolized via ring
      hydroxylation to form small amounts of hydroxymolinate. The amount of
      hydroxymolinate was substantially less in testis microsomes. Overall, these data
      indicate that sulfoxidation of molinate plays a role in molinat-induced
      testicular toxicity. Moreover, molinate is metabolized readily by both liver and
      testis microsomal enzymes, suggesting that the molinate toxic metabolite could be
      formed in the testis in close proximity to its site of action.

PMID- 9571985
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin and diethylstilbestrol affect thymocytes at
      different stages of development in fetal thymus organ culture.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and estrogen induce thymic atrophy and
      alter thymocyte development. In the present study we investigate whether TCDD and
      the synthetic estrogen diethylstilbestrol (DES) alter intrathymic development by
      the same or different mechanisms. We compared the effects of TCDD and DES on
      thymocyte development in fetal thymus organ culture (FTOC) and found that both
      compounds caused a reduction in cell yield. TCDD- and DES-treated FTOCs yielded
      fewer CD4 + CD8+ double-positive cells. However TCDD treatment also led to a
      greater percentage of cells in the CD8+ single-positive compartment. At lower
      dioxin concentrations, our results demonstrated an actual increase in CD8+ cells,
      whereas DES-treated fetal thymocytes were mainly enriched in CD4-CD8- double
      negative cells. More alpha beta-TCR+ positive cells were seen in TCDD- but not in
      DES-exposed cultures. Furthermore, in this study we found that TCDD and DES also
      alter intrathymic development at different stages in the CD4-CD8- double-negative
      compartment. TCDD induced a relative increase in c-kit + CD44 + CD25-HSA
      thymocytes, while DES induced an relative increase in c-kit-CD44-CD25 + HSA+
      cells. RT-PCR revealed that TCDD reduced RAG-1, RAG-2, and TdT gene expression in
      the CD4-CD8- double-negative thymocytes. Co-treatment by TCDD and DES in FTOC
      yielded a mixture of effects induced by each agent. Taken together, our results
      demonstrate that TCDD and DES affect thymocytes at different stages of
      development, suggesting distinct mechanisms for induction of thymic atrophy.

PMID- 9571986
TI  - Hydroquinone, a reactive metabolite of benzene, inhibits NF-kappa B in primary
      human CD4+ T lymphocytes.
AB  - Hydroquinone (HQ), a reactive metabolite of benzene, is present in cigarette
      smoke and is known to inhibit mitogen-stimulated activation of both T and B
      lymphocytes. Despite extensive study, the underlying mechanism for HQ's
      immunotoxicity is not clear. NF-kappa B is a transcription factor known to
      regulate the expression of a number of genes critical for normal T cell
      activation. We therefore hypothesized that NF-kappa B might be involved in HQ
      induced immunosuppression. In this study, we demonstrate that 1 microM HQ
      inhibits tumor necrosis factor alpha induced activation of NF-kappa B in primary
      human CD4+ T cells. This inhibition is not accompanied by a loss in viability,
      and HQ-treated T cells maintain other active signaling pathways throughout the
      exposure duration. Additionally, the inhibition of NF-kappa B is reversible as HQ
      treated T cells regain normal functioning after 72 h in culture. HQ does not
      appear to alter NF-kappa B directly as preincubation of nuclear extracts with HQ
      does not diminish activity of this protein. We further demonstrate that 1 microM
      HQ inhibits intracellular IL-2 production in T cells stimulated with phorbol
      ester but does not alter surface expression of CD25 (the alpha-subunit of the IL
      2 receptor). These data suggest that NF-kappa B may be an important molecular
      mediator of HQ's (and benzene's) immunotoxicity.

PMID- 9571987
TI  - Overexpression of HSP-70 attenuates increases in [Ca2+]i and protects human
      epidermoid A-431 cells after chemical hypoxia.
AB  - This laboratory previously reported that thermotolerance diminishes the NaCN
      induced increase in intracellular free calcium concentrations ([Ca2+]i) in human
      epidermoid A-431 cells and that blocking this increase protects the cells from
      NaCN toxicity. In this study, we report that cell viability after exposure to
      NaCN (10 mM, 1 h) is enhanced by the overexpression of HSP-70 resulting from heat
      shock (45 degrees C, 10 min), treatment with a protein kinase C activator phorbol
      12 myristate 13-acetate (PMA; 1 microM, 4 h), or HSP-70 cDNA transfection.
      Because the toxicity of NaCN is mediated by increases in [Ca2+]i, we sought to
      determine whether the overexpression of HSP-70 might protect the cells by
      altering the [Ca2+]i response induced by NaCN. Basal [Ca2+]i in vector-, HSF1
      cDNA-, and HSP-70 cDNA-transfected cells was 114 +/- 11 (n = 11), 95 +/- 5 (n =
      6), and 151 +/- 11 (n = 15) nM, respectively, suggesting that HSP-70 metabolism
      is associated with maintenance of resting [Ca2+]i. Removal of external Ca2+
      reduced the resting [Ca2+]i in all of these cells. With external Ca2+ reduced the
      resting [Ca2+]i by 97 +/- 21% in vector-transfected cells and 111 +/- 5% in HSF1
      vector-transfected cells but by only 27 +/- 8% in HSP-70 cDNA-transfected cells.
      Heat shock or PMA treatment of vector- or HSF1 cDNA-transfected cells to induce
      HSP-70 also attenuated the NaCN-induced increase in [Ca2+]i, perhaps because of a
      decrease in Vmax for the uptake of external Ca2+. Removal of external Ca2+ or
      treatment with inhibitors of Na+/Ca2+ exchangers eliminated the NaCN-induced
      increase in [Ca2+]i in HSP-70 cDNA-transfected cells, but ryanodine treatment did
      not. HSP-70 cDNA transfection also reduced Ca2+ mobilization stimulated by
      various Ca(2+)-mobilizing agents. The results suggest that HSP-70 overexpression
      protects cells from NaCN cytotoxicity, perhaps by attenuating the [Ca2+]i
      response.

PMID- 9571988
TI  - Cytochrome P450 2E1 in rat tracheobronchial airways: response to ozone exposure.
AB  - The distal trachea and centriacinus of the lung are primary sites of acute injury
      during short-term ozone exposure; long-term exposure yields cells in these areas
      that are resistant to high doses of oxidant gases. Epithelial cells located in
      primary sites for ozone injury are also targets for chemicals that undergo
      cytochrome P450 (CYP)-dependent activation. These studies were designed to
      compare the effects of ozone exposure on pulmonary CYP2E1 in susceptible and
      nonsusceptible sites within the airway tree of lung. CYP2E1 activity was measured
      in well-defined regions of airways using p-nitrophenol, a CYP2E1-selective
      substrate, with HPLC/ electrochemical detection of the p-nitrocatechol.
      Alterations in distribution of CYP2E1 were evaluated by immunohistochemistry.
      CYP2E1 activities were highest in the distal bronchioles and minor daughter
      airways but were much lower in the lobar bronchi/ major daughter airways and
      trachea. Immediately after short-term ozone exposures (8 h, 1 ppm), CYP2E1
      activities were elevated only in the lobar bronchi/major daughter airways. These
      activities remained above the filtered air control at 1 day but returned to
      control levels by 2 days. Immunohistochemical assessment of CYP2E1 protein in
      ozone and filtered air-exposed animals was consistent with the activity
      measurements. After long-term ozone exposures (90 days, 1 ppm), CYP2E1 activities
      were decreased in the major and minor daughter airways. These studies indicate
      that CYP2E1 activities vary substantially by airway level. However, ozone
      exposure only results in minimal alterations in activity with varying
      concentration of ozone, length of exposure, and time after exposure in any of the
      lung subcompartments examined.

PMID- 9571989
TI  - Cadmium-induced apoptosis in mouse liver.
AB  - Apoptosis is a process of active cell death, distinct from necrosis and
      characterized by specific morphological and biochemical features. Although the
      acute hepatotoxic effects of cadmium (Cd) are well described, little is known
      about the occurrence of apoptosis in Cd toxicity. Therefore, mice were injected
      with 5-60 mumol/kg i.p. of Cd and their livers were removed 1.5-48 h later and
      examined by light microscopy. Cd induced both a time- and dose-dependent increase
      in apoptotic index, severity of necrosis, and mitotic index. Apoptotic index
      peaked at 9-14 h after Cd administration and then decreased. The time course of
      apoptotic DNA fragmentation index, monitored by quantification of
      oligonucleosomal DNA fragments, correlated with the results obtained by
      histopathological analysis and a commercial in situ apoptotic DNA detection kit.
      Liver necrosis, as demonstrated by histology and serum alanine aminotransferase
      and sorbitol dehydrogenase assays, was most severe 14-48 h after Cd injection.
      Apoptosis was decreasing by 24 h while necrosis persisted. Replacement of liver
      tissue by blood lakes (peliosis hepatis) was observed after 14 h. The mitotic
      index increased gradually with time, indicating compensatory liver cell
      regeneration. There was a progressive increase in the severity of necrosis,
      apoptotic index, and mitotic index with increasing dose of Cd. These data
      demonstrate that apoptosis is a major mode of elimination of critically damaged
      cells in acute Cd hepatotoxicity in the mouse, and it precedes necrosis.

PMID- 9571990
TI  - Suppression of fibroblast cell cycle progression in G1 phase by N-acetylcysteine.
AB  - The antioxidant N-acetyl-L-cysteine (NAC) has been increasingly used as an
      experimental tool to assess involvement of reactive oxygen species in cell
      signaling and is being evaluated as a preventive and therapeutic agent for cancer
      and pulmonary diseases related to inflammation and oxidative stress. However, a
      detailed characterization of the effect of NAC on cell cycle progression has not
      been reported. In the present study, modulation of cell cycle progression by NAC
      was analyzed in mouse fibroblast NIH3T3 cells grown in 10% fetal bovine serum.
      Complete inhibition of NIH3T3 cell proliferation was obtained with 20 mM NAC.
      Inhibition of cell proliferation by NAC (at or below 20 mM) was not due to cell
      death, and the antiproliferative effect of NAC was reversible. Flow cytometric
      analysis of cell cycle phase distribution indicated that NAC blocked the cell
      cycle in the G1 phase. Consistent with this observation, NAC inhibited DNA
      synthesis. After releasing the G1-block by NAC, S phase re-entry occurred between
      8 and 12 h, suggesting that NAC blocked the cell cycle in early to mid-G1 phase.
      NAC prevented activation of mitogen-activated protein (MAP) kinases p42MAPK and
      p44MAPK and inhibited expression of cyclin D1, but had no effect on the levels of
      proliferating cell nuclear antigen. Incubation of cells with PD98059, a specific
      inhibitor of MAP kinase kinase 1, partially arrested the cell cycle in the G1
      phase. These results indicate that the antiproliferative effect of NAC is linked
      in part to inhibition of the MAP kinase pathway.

PMID- 9571991
TI  - Chloroform-induced cytolethality in freshly isolated male B6C3F1 mouse and F-344
      rat hepatocytes.
AB  - Chloroform is carcinogenic in rodents but is not mutagenic or DNA reactive.
      Chloroform-induced hepatocarcinogenesis in rodents is believed to be secondary to
      events associated with cytotoxicity and cell proliferation. Understanding the
      mechanisms of chloroform toxicity may provide insights into the mechanisms of
      carcinogenicity. The goal of these studies was to characterize the cytotoxicity
      of chloroform in male B6C3F1 mouse and F-344 rat hepatocytes in vitro. We used an
      in vitro suspension-culture system that reproduced the exposure of the liver to
      chloroform and the expression of toxicity in vivo. Simulations of a
      physiologically based dosimetry model for chloroform indicated that the livers of
      mice and rats were exposed to chloroform concentrations up to 5 mM for 3 h after
      hepatotoxic doses of chloroform. Freshly isolated male mouse and rat hepatocytes
      were exposed to chloroform in sealed flasks and then cultured for 24 h as
      monolayers. Following a 2- or 3-h exposure in suspension, chloroform induced
      concentration-dependent cytotoxicity (lactate dehydrogenase release) in culture
      at concentrations higher than 1 mM. Cytolethality was not increased under reduced
      oxygen tension, indicating that reductive metabolism does not contribute to
      chloroform-induced toxicity. A threshold of 1 mM chloroform was also found for
      glutathione (GSH) depletion, with a 50% depletion at 3.8 mM after 2 h. Addition
      of dithiothreitol, a reducing agent, did not prevent chloroform-induced toxicity,
      indicating that oxidation of sulfhydryl groups is not critical for toxicity. The
      lack of protein sulfhydryl group depletion is consistent with this conclusion.
      Cotreatment with the cytochrome P450 inhibitor 1-phenylimidazole prevented both
      cytolethality and GSH depletion, indicating that metabolism is necessary for
      chloroform-induced toxicity. Both species exhibited similar sensitivity toward
      chloroform toxicity, indicating that toxicity is not sufficient to explain
      different susceptibility in heptocarcinogenicity. As chloroform metabolism is
      saturated in the micromolar range, our results indicate that both metabolism and
      exposure of the liver cells to high concentrations of chloroform are required for
      toxicity.

PMID- 9571992
TI  - Identification of a carboxylesterase as the major protein bound by molinate.
AB  - Molinate, a herbicide widely used on rice, has been previously shown to cause
      testicular toxicity when a single dose is administered to Sprague-Dawley rats.
      The sulfoxide metabolite of molinate also was capable of eliciting testicular
      damage but at lower dose levels than molinate, suggesting that metabolic
      activation via sulfoxidation could be important in testicular toxicity. Both the
      sulfoxide and sulfone metabolites of molinate are electrophilic and molinate
      covalent binding to cellular macromolecules has been attributed to formation of
      these reactive metabolites. The present study has investigated the nature of the
      binding reaction of 14C-molinate as well as 14C-molinate sulfoxide and 14C
      molinate sulfone in liver and testis microsomal preparations. All three compounds
      in preparations from both tissues bound extensively and tightly to only one
      protein of approximately 60 kDa molecular weight on SDS-PAGE. Isoelectric
      focusing PAGE revealed a pI of approximately 6.0 and native PAGE analysis
      revealed a native molecular weight of 180 kDa. These data, along with the ability
      of phenylmethylsulfonyl fluoride to block binding of the 14C-molinate, suggested
      the molinate-bound protein was an esterase. The protein was purified to
      homogeneity and MALDI-TOF mass spectral analysis was consistent with Hydrolase A,
      a carboxylesterase present in both liver and testis. N-terminal sequence analysis
      revealed 100% homology with Hydrolase A for the first 17 residues. The effect of
      molinate administration on in vivo esterase activity was assessed both by
      enzymatic measurement and by histochemical measurement. Molinate treatment caused
      a marked inhibition of nonspecific esterase activity in both liver and testis. In
      the testis, histochemical staining showed the esterase activity inhibited by
      molinate was localized primarily to the Leydig cell, consistent with the
      localization of Hydrolase A. From these data, it is proposed that molinate
      induced inhibition of esterase activity in the Leydig cell could inhibit the
      mobilization of cholesterol esters required for testosterone biosynthesis.

PMID- 9571993
TI  - Chemically induced platelet lysis causes vasoconstriction by release of
      serotonin.
AB  - Our previous studies have shown that menadione is cytotoxic to platelets, leading
      to substantial release of vasoactive substances. To test whether platelet lysis
      induced by menadione could cause vasoconstriction, we investigated the effect of
      platelet lysate induced by menadione on rat aorta in organ bath system. We showed
      that menadione-induced platelet lysate caused vasoconstriction in a dose- and
      time-dependent manner. These effects were seen in aortic rings both with and
      without endothelium, but it was much greater in rings without intact endothelium.
      The time course of vasoconstriction was well correlated with the time courses of
      platelet lysis (assessed by lactate dehydrogenase release) as well as serotonin
      release. The vasoconstriction by platelet lysate was blocked by serotonin
      antagonists, ketanserin, and LY53,857, but not by thromboxane A2 (TXA2) receptor
      antagonist, SQ29,548, suggesting that vasoconstriction mainly occurred secondary
      to the release of serotonin in our in vitro system. However, potentiation of
      vasoconstriction by combined treatment of serotonin and a stable TXA2 mimic,
      U46619, suggests the possibility of the increased risk for vasoconstriction in
      vivo. In addition, the serotonin-induced vasoconstriction was potentiated by
      residual menadione present in the organ bath. These results suggest that
      chemically induced platelet cytotoxicity can provoke alteration in vasomotor tone
      by release of serotonin.

PMID- 9571994
TI  - Effect of organic forms of selenium on delta-aminolevulinate dehydratase from
      liver, kidney, and brain of adult rats.
AB  - The inhibitory effect of various forms of organic selenium compounds and of
      diphenyl ditelluride (PhTe)2 on delta-aminolevulinate dehydratase (delta-ALA-D)
      from liver, kidney, and brain of rats was investigated because it has been
      reported that organocalcogens catalyze the oxidation of thiols. Diphenyl
      diselenide (PhSe)2, rho-chloro-diphenyl diselenide (rho ClPhSe)2, propyl-2-2
      diphenyl diselenide, and propyl-2-methoxy-2-phenyl selenide inhibited delta-ALA-D
      and the IC50 ranged from 2 to 32 microM depending on the selenium compound and
      whether it was preincubated with the enzyme. (rho ClPhSe)2 was the most potent
      inhibitor of delta-ALA-D, and preincubation increased the inhibitory potency of
      all the tested compounds. Inorganic selenium compounds (sodium selenite, Na2SeO3
      and selenium dioxide, SeO2) inhibited delta-ALA-D, and the potency of SeO2 was
      greater than that of (rho ClPhSe)2. Diphenyl ditelluride (PhTe)2 also inhibited
      delta-ALA-D but with relatively lower potency than that of organic and inorganic
      selenium compounds. The inhibitory effect of propyl-2-2-diphenyl diselenide and
      propyl-2-methoxy-2-phenyl selenide seems to be mediated by (PhSe)2 since the
      compounds decomposed rapidly to (PhSe)2 in aqueous medium. The inhibitory action
      of selenium forms on delta-ALA-D from liver, kidney, and brain was antagonized by
      sulfhydryl protecting agents (dithiotreitol and reduced glutathione). The effects
      of organic selenium compounds on delta-ALA-D were related to the stability of the
      Se-Se (or Se-C) bond because the compound methyl-diphenyl diselenide (which
      possesses the most stable Se-C-Se bond) did not inhibit the enzyme. The
      inhibitory action of (PhSe)2 was not related to the formation of oxyradicals in
      the medium since superoxide dismutase and catalase did not affect the inhibition
      of delta-ALA-D by (PhSe)2. delta-ALA-D from cucumber leaves was not inhibited by
      selenium or tellurium compounds which suggests that these compounds act directly
      on the B or beta-site of the animal enzyme. These results suggest that delta-ALA
      D from liver, kidney, and brain is a potential molecular target for the toxic
      effect of organic forms of selenium and tellurium.

PMID- 9571995
TI  - Temporal changes in tissue repair upon repeated exposure to thioacetamide.
AB  - In an earlier study it was reported that a single low dose of thioacetamide (TA,
      50 mg/kg) administered 36 h prior to challenge with a high dose of 400 mg/kg
      offers protection from lethality of high dose (Mangipudy et al., Pharmacol.
      Toxicol. 77, 1995). The mechanism underlying this protection was found to be
      preplaced hepatocellular division and tissue repair that peaked by 36 h following
      the low-dose treatment. In a separate study using the dose-response paradigm, it
      was established that the rate and the extent of the tissue repair response
      following infliction of injury after acute exposure has a critical bearing on the
      ultimate outcome of toxicity (Mangipudy et al., Environ. Health Perspect. 103,
      1995). The objective of this study was to investigate the cell proliferation
      dynamics after repeated exposure to TA (50 mg/kg i.p.). Male Sprague-Dawley rats
      (200-225 g) were administered TA at intervals of 96 h. Liver injury and tissue
      repair were studied over a time course following each treatment. Tissue repair
      was estimated by S-phase DNA synthesis measuring 3H-thymidine incorporation into
      hepatonuclear DNA while liver injury was estimated by serum alanine
      aminotransferase activity. After the first dose of 50 mg/kg, peak S-phase DNA
      synthesis was observed at 36 h. This returned to control values by 96 h at which
      time the rats are known to overcome liver injury. A second dose of TA (repeated
      dose 1, RD1) resulted in peak S-phase DNA synthesis 12 h later at 48 h. Following
      the third dose (RD2) a dramatic increase in S-phase DNA synthesis was noted from
      as early as 12 h. Much higher peak was observed at 72 h. Interestingly, following
      the fourth dose (RD3) S-phase stimulation did not occur. Instead, a significant
      latency was observed for cells in the S-phase DNA synthesis even at time points
      as late as 144 h following the treatment. Liver injury on the other hand
      exhibited no significant differences between repetitions until RD2. However,
      injury was sustained in the rats treated with the fourth dose (RD3) while it
      returned to control levels in the earlier three instances. Sustained prolongation
      of liver injury after the fourth dose is presumably because tissue repair was not
      operational. Thus repeated exposure to TA causes a significant increase in tissue
      repair response although it is temporally delayed until a threshold is reached.
      Repetition beyond the threshold results in a marked attenuation of the repair
      response. These findings suggest that toxicodynamics of cell proliferation are
      altered after repeated exposure.

PMID- 9571996
TI  - Prevalence of sarcoidosis around the world.

PMID- 9571997
TI  - Treatment of sarcoidosis with corticosteroids: who is going to relapse and why?

PMID- 9571998
TI  - Dysphoria and sarcoidosis.

PMID- 9571999
TI  - Serum markers for the staging of disease activity of sarcoidosis and other
      interstitial lung diseases of unknown etiology.
AB  - Immunopathogenic mechanisms in sarcoidosis, idiopathic pulmonary fibrosis, and
      pulmonary manifestations of collagen-vascular diseases maintain an alveolitis
      which may lead to irreversible organ damage. The classical parameters used in the
      management of pulmonary involvement of these disorders are chest X-ray and
      pulmonary function test which do not gauge alveolitis but rather pulmonary
      impairment. From the immunopathogenesis several serological parameters have been
      delineated estimating different aspects of inflammatory processes. Cytokines,
      soluble cytokine receptors, metabolites, enzymes, extracellular matrix
      components, soluble adhesion molecules, and other serum components have been
      evaluated to serve as serological markers of alveolitis. The mechanisms gauged by
      these markers, and their clinical usefulness are discussed in this review.

PMID- 9572000
TI  - Lipocortin I gene expression is higher in blood monocytes than in BAL fluid
      macrophages in patients with pulmonary sarcoidosis.
AB  - BACKGROUND AND AIM OF WORK: Lipocortin I, induced by corticosteroids in vivo is
      considered to be related to cell activation and differentiation in mononuclear
      phagocytes, key cells in the process of epithelioid cell granuloma formation in
      sarcoidosis. Therefore, we focused on the expression of lipocortin I gene in
      mononuclear phagocytes in patients with sarcoidosis. METHOD: The amounts of
      transcripts of lipocortin I gene obtained from both BAL fluid macrophages and
      blood monocytes were measured by RT-PCR and HPLC, and then standardized as the
      ratio of lipocortin I/beta-actin for comparison. RESULTS: 1. Smoking did not
      affect the expression of lipocortin I gene in BAL fluid macrophages and
      monocytes. 2. There were no differences in the amounts of expression in BAL fluid
      macrophages between patient groups (nonsmokers and smokers), or between patients
      and healthy subjects. 3. The gene expression in BAL fluid macrophages was higher
      than that in monocytes in patients with IPF (macrophages 1.23 +/- 0.48, vs
      monocytes 0.50 +/- 0.38, p < 0.05) and healthy subjects (nonsmokers: 1.66 +/-
      1.17, vs 0.34 +/- 0.26, p < 0.05, smoker: 1.98 +/- 0.96, vs 0.34 +/- 0.48, p <
      0.05, but sarcoidosis patients showed a higher expression of lipocortin I gene
      even in monocytes (2.62 +/- 1.87, vs 2.66 +/- 2.21). CONCLUSION: The increase in
      lipocortin I gene expression in monocytes was a disease-related finding in
      sarcoidosis.

PMID- 9572001
TI  - Sarcoidosis in coroner's autopsies: a critical evaluation of diagnosis and
      prevalence from Cuyahoga County, Ohio.
AB  - BACKGROUND AND AIM OF THE WORK: During a histologic study of sarcoidosis in
      tissues made available from the Cuyahoga County Coroner's autopsy files, the
      prevalence of this disorder seemed much greater than generally reported. Aims
      were to evaluate this impression and if confirmed, to explore underlying reasons,
      including reliability of diagnoses and possible overestimates as well as possible
      associations with particular population subgroups. METHODS: Cases were retrieved
      by computer search of diagnoses coded over the past 7 years. Extent of organ
      involvement was documented and relevant microscope slides reviewed, with
      consideration of diagnostic criteria generally proposed. Clinical information,
      occupational risk and evidence for illicit drug use were evaluated. Acceptable
      cases were categorized by gender, race and age. Crude and standardized
      prevalences were calculated and related to 1990 US Census figures for the County.
      RESULTS: On review of 9324 adult autopsies performed for medico-legal reasons, 31
      were judged to have sarcoidosis. Standardized prevalence was 320 +/- 72/10(5).
      Among population subgroups statistically significant differences were not
      established. However, crude prevalences suggested that females, blacks and
      younger persons were more likely to have sarcoidosis than males, whites and older
      subjects, with ratios of 1.6 to 1; 4.7 to 1; and 2.5 to 1, respectively. Overall
      prevalence was some 10 times greater than indicated from State-wide death
      certificates. CONCLUSIONS: Sarcoidosis as found in cases autopsied at
      the/Coroner's Office, Cuyahoga County, is much more prevalent than generally
      reported. It is an under-appreciated cause of sudden unexpected death. Young
      black females appear to be most affected, and worthy of further investigation.

PMID- 9572002
TI  - The late follow-up of chronic sarcoid patients previously treated with
      corticosteroids.
AB  - AIM OF THE STUDY: The aim of the study was to evaluate, in a white population
      with chronic sarcoidosis, the rate and pattern of relapses, the correlated
      factors, and the course of disease after prednisone withdrawal. METHODS: We have
      retrospectively examined the charts of 702 consecutive patients with
      histologically proven sarcoidosis, first seen in the Milan Sarcoidosis Clinic in
      the period October 1978-October 1994. 239 patients required corticosteroid
      therapy; in 82 it was possible to discontinue prednisone therapy and to have a
      follow-up of at least 18 months after withdrawal. RESULTS: A relapse, requiring a
      new course of steroids, was observed in 30 (36.6%) of the 82 patients (R group).
      The other 52 patients (No-R group) did not relapse during a mean follow-up of
      36.8 +/- 24.8 months (range 18-125). There were no relapses after 3 asymptomatic
      years of prednisone withdrawal. Extrapulmonary sarcoidosis was a reason for
      giving therapy in 46.6% of patients in the R group, vs 23.0% in the No-R group (P
      < 0.05). The first course of therapy lasted 22 months [median time; i.q. 11.5 to
      34.5] in R group vs 26 months [i.q. 18 to 41] in No-R group (P > 0.05). The mean
      daily prednisone dose was higher in the R group: 17 mg [median value; i.q. 8.9 to
      23.2] vs 10.6 mg [i.q. 8.1 to 13.8] in the No-R group (p < 0.05). Logistic
      regression confirmed the prognostic significance of mean daily prednisone dose
      and of extrapulmonary sarcoidosis at presentation (P < 0.01). A mild sarcoid
      activity at the time of withdrawal was still present in 51.9% of patients who did
      not relapse, and in 66.7% of patients who relapsed (p > 0.05). Relapse in the
      first year after withdrawal of prednisone therapy occurred in twenty-five of the
      30 patients. The pattern of relapse was different from the initial manifestation
      in 5. Nine of the 30 patients could ultimately be weaned successfully from
      prednisone. CONCLUSION: Relapses occurred in 36.6% of cases, and their pattern
      was the same as the initial manifestation in the majority of cases. A mild
      sarcoid activity at the time of withdrawal is not a reason for continuing
      steroids when the disease is abating. In our white population severe irreversible
      pulmonary impairment is rare, and even patients requiring chronic therapy need
      low prednisone dosage, usually around 10 mg daily, to control the disease in the
      late course.

PMID- 9572003
TI  - Quality of life and depressive symptoms in patients suffering from sarcoidosis.
AB  - BACKGROUND: Apart from the disease status, chronically ill patients are
      confronted with stressors like dependence, limitations in mobility and physical
      complaints. Data on patients with sarcoidosis, however, are lacking. The aim of
      this study was to investigate the quality of life (QOL) and the influence of QOL
      factors on depressive symptoms in these patients. PATIENTS AND METHODS: Sixty
      four patients with histologically proven sarcoidosis participated in this study.
      Significant co-morbidity was excluded. The Sickness Impact Profile (SIP) was used
      to determine the QOL. Depressive symptoms were measured with the Beck Depression
      Inventory (BDI), of which a subset of items measured cognitive symptoms, the
      Cognitive Depression Index (CDI). Disease status was assessed by pulmonary
      function parameters (FEV1, Dco), complaints and illness duration. To control for
      a confounding cognitive style of self-report, the Positive Affect Negative Affect
      Schedule (PANAS) was administered. RESULTS: The major complaint was fatigue. QOL
      was related to the perception of complaints, but not to the assessed disease
      status. In a multivariate regression 86% of the variance could be explained in
      BDI-scores, and 83% in CDI-scores. After controlling for demographical factors,
      disease status and cognitive style, QOL contributed to the regression, explaining
      another 17% of variance of BDI-scores as well as CDI-scores. Problems with
      sleeping were associated positively with depressive symptoms in general (beta =
      0.38) and depressive cognitions only (beta = 0.32). CONCLUSIONS: In sarcoidosis,
      QOL factors were associated with depressive symptoms. These results suggest that
      patients with sarcoidosis may profit from attention to the psychosocial as well
      as the somatic aspects of this disease.

PMID- 9572004
TI  - Contemporaneous acute myeloid leukaemia and sarcoidosis. Report of three cases.
AB  - Three cases of contemporaneous acute myeloid leukaemia (AML) and sarcoidosis are
      described. The possible pathogenic mechanisms concerning their concurrent
      appearance are discussed: if sarcoidosis impaired T-cell response, it could
      perhaps predispose the development of AML; alternatively, the development of
      sarcoidosis during AML may be due to a reaction linked to a diffuse release of
      tumour antigens with a subsequent formation of a non-caseating granulomata.

PMID- 9572005
TI  - Hailfinder. Tools for and experiences with Bayesian normative modeling.
AB  - Bayes Nets (BNs) and Influence Diagrams (IDs), new tools that use graphic user
      interfaces to facilitate representation of complex inference and decision
      structures, will be the core elements of new computer technologies that will make
      the 21st century the Century of Bayes. BNs are a way of representing a set of
      related uncertainties. They facilitate Bayesian inference by separating
      structural information from parameters. Hailfinder is a BN that predicts severe
      summer weather in Eastern Colorado. Its design led to a number of novel ideas
      about how to build such BNs. Issues addressed included representation of spatial
      location, categorization of days, system boundaries, pruning, and methods for
      eliciting and checking on the appropriateness of conditional probabilities. The
      technology of BNs is improving rapidly. Especially important is the emergence of
      ways of reusing fragments of BNs. BNs and IDs are not just important design
      tools; they also represent a major enhancement of the understanding about how
      important intellectual tasks typically performed by people should and can be
      performed.

PMID- 9572006
TI  - Harnessing the imagination. Mental simulation, self-regulation, and coping.
AB  - Mental simulation provides a window on the future by enabling people to envision
      possibilities and develop plans for bringing those possibilities about. In moving
      oneself from a current situation toward an envisioned future one, the
      anticipation and management of emotions and the initiation and maintenance of
      problem-solving activities are fundamental tasks. In the program of research
      described in this article, mental simulation of the process for reaching a goal
      or of the dynamics of an unfolding stressful event produced progress in achieving
      those goals or resolving those events. Envisioning successful completion of a
      goal or resolution of a stressor--recommendations derived from the self-help
      literature--did not. Discussion centers on the characteristics of effective and
      ineffective mental simulations and their relation to self-regulatory processes.

PMID- 9572007
TI  - In search of cultural competence in psychotherapy and counseling.
AB  - The characteristics involved in cultural competency in psychotherapy and
      counseling have been difficult to specify. This article describes attempts to
      study factors associated with cultural competency and addresses 3 questions.
      First, is ethnic match between therapists and clients associated with treatment
      outcomes? Second, do clients who use ethnic-specific services exhibit more
      favorable outcomes than those who use mainstream services? Third, is cognitive
      match between therapists and clients a predictor of outcomes? The research
      suggests that match is important in psychotherapy. The cultural competency
      research has also generated some controversy, and lessons learned from the
      controversy are discussed. Finally, it is suggested that important and orthogonal
      ingredients in cultural competency are therapists' scientific mindedness, dynamic
      sizing skills, and culture-specific expertise.

PMID- 9572008
TI  - Teaching critical thinking for transfer across domains. Dispositions, skills,
      structure training, and metacognitive monitoring.
AB  - Advances in technology and changes in necessary workplace skills have made the
      ability to think critically more important than ever before, yet there is ample
      evidence that many adults consistently engage in flawed thinking. Numerous
      studies have shown that critical thinking, defined as the deliberate use of
      skills and strategies that increase the probability of a desirable outcome, can
      be learned in ways that promote transfer to novel contexts. A 4-part empirically
      based model is proposed to guide teaching and learning for critical thinking: (a)
      a dispositional component to prepare learners for effortful cognitive work, (b)
      instruction in the skills of critical thinking, (c) training in the structural
      aspects of problems and arguments to promote transcontextual transfer of critical
      thinking skills, and (d) a metacognitive component that includes checking for
      accuracy and monitoring progress toward the goal.

PMID- 9572009
TI  - Graduate education in clinical psychology. "We're not in Kansas anymore".
AB  - In this article, the author addresses changes impacting graduate education in
      clinical psychology, including those in technology, the academy, and the
      marketplace, and discusses implications of these changes for psychology.
      Significant concerns are raised concerning issues of supply and demand as well as
      the nature of the product of graduate education and training.

PMID- 9572010
TI  - Women and psychology. An international perspective.
AB  - This article examines the status of women in psychology internationally. Earlier
      research is reviewed and compared with recent findings, including a survey
      responded to by 40 individuals from countries around the world. Although
      improvements for women have been noted in many areas, problems of sexism and
      antifeminism still exist. The importance of comparative analyses across countries
      because of increasing worldwide interaction among psychologists is noted.

PMID- 9572012
TI  - The XIX Congress of the International Society for Analytical Cytology. Colorado
      Springs, Colorado, USA. 28 February-5 March 1998. Abstracts.

PMID- 9572011
TI  - Beyond self-interest. Professional advocacy and the integration of theory,
      research, and practice.

PMID- 9572013
TI  - European Respiratory Society Annual Congress. Berlin, Germany, September 20-24,
      1997. Abstracts.

PMID- 9572014
TI  - International Congress XI on Endovascular Interventions. February 8-12, 1998.
      Abstracts.

PMID- 9572016
TI  - Annual author and subject indexes to volumes 490-497 (January-December 1996).

PMID- 9572015
TI  - The Alimentary Disease Week. 9th International Conference on Ulcer Research, 4th
      International Conference of Gastroenterology, 3rd Asian AGA Course on
      Gastroenterology. Hong Kong, China. December 12-17, 1997. Abstracts.

PMID- 9572017
TI  - Society for Gynecologic Investigation 45th Annual Meeting. Atlanta, Georgia, USA.
      March 11-14, 1998. Abstracts.

PMID- 9572018
TI  - 9th Biennial Winter Workshop on Schizophrenia. Davos, Switzerland, February 7-13,
      1998. Abstract.

PMID- 9572020
TI  - Reduced intravascular catheter-related infection by routine use of antibiotic
      bonded catheters in a surgical intensive care unit.
AB  - We report a comparative analysis of intravascular catheter-related infection
      before and after routine use of antibiotic-bonded catheters in an intensive care
      unit. Cefazolin-bonded catheters were placed in patients requiring
      catheterization for at least 3 days, or with remote infection, standard catheters
      at other times. One thousand forty-five catheters (259 patients) over 6 months
      were compared with 801 (236 antibiotic-bonded, 565 standard) catheters (239
      patients) the next 6 months. After use of antibiotic-bonded catheters, we found:
      1.7% catheters infected versus 3.7% (p = 0.01); catheter-associated bacteremia
      0.1% versus 1.3% (p < 0.005); catheter-related infection rate 4.39 versus 10.73
      per 1000 patient days (p < 0.005), and 5.06 versus 11.47 per 1000 catheter days
      (p < 0.01); and cumulative risk of infection decreased (p < 0.005). Antibiotic
      bonded catheters were used with more remote infections (52% versus 27%, p <
      0.001), had longer indwelling time (4.4 versus 3.1 days, p = 0.0001), and more
      were inserted over a guide wire (66% vs. 28%, p < 0.001). In conclusion routine
      use of antibiotic-bonded catheters was associated with a significant reduction in
      infectious complications.

PMID- 9572021
TI  - Identification and natural antibiotic susceptibility of Morganella morganii.
AB  - Our data should elucidate whether or not natural antibiotic susceptibility can be
      used as an aid for subspecies or biovar discrimination of Morganella morganii
      (II). Furthermore, our goal was to create a database of the natural
      susceptibility of M. morganii (III) and we were interested in the relative
      frequency of the recently described subspecific taxa (I). On the basis of
      trehalose fermentation (TRE), ornithine decarboxylase (ODC), and lysine
      decarboxylase (LDC) activities, we determined the biovar for 90 clinical isolates
      of M. morganii. Within these strains we examined the natural antibiotic
      susceptibility of 53 morganellae to 70 antibiotics by determination of the MICs
      with a microdilution procedure. (I): 80 strains (89%) of all morganellae belonged
      to M. morganii ssp. morganii (TRE-), with biovar A (LDC-, ODC+) predominating (67
      strains). The remaining strains of this subspecies were identified as biovar B
      (LDC+, ODC+; 12 strains) and biovar C (LDC-, ODC-, one strain). Ten strains of M.
      morganii ssp. sibonii (TRE+) were found: four strains belonged to biovar F (LDC
      variable, ODC-) and six strains to biovar G (LDC-, ODC). (II): With one exception
      we found no significant differences in antibiotic susceptibility between
      different biovars. M. morganii ssp. morganii strains are more susceptible to
      tetracycline than strains of M. morganii ssp. sibonii, but there is no evidence
      that this parameter could be useful to differentiate biovars within a subspecies.
      It could be shown that 8 of 30 strains of biovar A and 2 of 12 strains of biovar
      B were tetracycline resistant. However, one M. morganii ssp. sibonii strain was
      clinically susceptible to tetracycline according to French and American
      standards. (III): The natural population of M. morganii is primarily (naturally)
      resistant to certain penicillins like benzylpenicillin, oxacillin, and
      amoxicillin, first and second generation cephalosporins (excluding cefoxitin),
      cefpodoxime, all antibiotics of the ML group (macrolides and lincosamides),
      sulfamethoxazole, glycopeptides, fosfomycin, and fusidic acid, naturally
      sensitive to aminoglycosides, piperacillin, mezlocillin, ticarcillin, third and
      fourth generation cephalosporins, carbapenems, aztreonam, quinolones,
      trimethoprim, cotrimoxazole, and chloramphenicol. M. morganii is naturally
      resistant to a wide range of antibiotics. The natural resistance pattern is
      useful for validation of sensitivity tests. Susceptibility to antibiotics is an
      unsuitable parameter for the discrimination of the described subspecific taxa of
      M. morganii. M. morganii strains that do not belong to biovar A are rare.

PMID- 9572022
TI  - Use of random amplified polymorphic DNA for rapid molecular subtyping of
      Corynebacterium diphtheriae.
AB  - A total of 210 Corynebacterium diphtheriae strains isolated worldwide were
      assayed by random amplified polymorphic DNA (RAPD) assay. RAPD was as
      discriminating as standard ribotyping, and in some cases, even further
      differentiation was obtained. RAPD can rapidly aid clinical and molecular
      epidemic studies in a simple and cost-effective manner.

PMID- 9572023
TI  - Sensitivity of two enzyme-linked immunosorbent assay tests in relation to western
      blot in detecting human T-cell lymphotropic virus types I and II infection among
      HIV-1 infected patients from Sao Paulo, Brazil.
AB  - We investigated the presence of human T-cell lymphotropic virus types I and II
      (HTLV-I and HTLV-II) infections, first searching for specific antibodies in 553
      serum samples obtained from HIV-1-infected patients from Sao Paulo, Brazil. Sera
      were screened using two enzyme-linked immunosorbent assays (ELISAs): the ELISA-EM
      (ELISA HTLV-I/II, EMBRABIO, BR), which contains HTLV-I and HTLV-II lysates, and
      the ELISA-DB [ELISA HTLV-I/II, Diagnostic Biotechnology (DB), Singapore], which
      contains HTLV-I lysate, and HTLV-I and HTLV-II recombinant env proteins (MTA-1
      and K55, respectively). Serum samples showing two positive and/or borderline
      results were confirmed by Western blot (WB 2.3, DB), which discriminates HTLV-I
      from HTLV-II. WB analyses disclosed 22 cases (4.0%) of HTLV-I and 34 (6.1%) of
      HTLV-II seroreactivity; 24 sera had indeterminate antibody profile (4.3%) and 2
      specimens showed reactivity to both MTA-1 and K55 env proteins. Using stringent
      WB criteria and analyzing the population according to risk factors, the
      prevalence rates of HTLV-I and HTLV-II infections were 11.2% and 16.8% in i.v.
      drug users, 3.4% and 5.5% in heterosexual individuals, and 1.4% and 2.2% in
      homosexual/bisexual men, respectively. A comparison of ELISA and WB results
      disclosed that both ELISAs were highly sensitive in detecting HTLV-I antibodies,
      whereas the ELISA-DB showed 82% sensitivity and the ELISA-EM 100% sensitivity in
      detecting HTLV-II antibodies. PCR analyses conducted on 37 representative cells
      samples confirmed the presence of HTLV proviral DNA in the majority of concordant
      serological cases, except in one, which was HTLV-I infected and seroreacted with
      K55 protein of HTLV-II. Indeed, after PCR, one case of HTLV-I infection and HTLV
      II coinfection, and 30% of WB-seroindeterminate or inconclusive cases infected
      with HTLV-II could be detected. Our data stress high prevalences of both HTLV-I
      and HTLV-II infections in HIV-1 coinfected i.v. drug users from Sao Paulo, and
      suggests that ELISA kits containing only K55 protein as the HTLV-II-specific
      antigen, may not have the appropriate sensitivity for the detection of HTLV-II
      infection in this geographic region, pointing out the need of improved screening
      tests to be used in Brazil.

PMID- 9572024
TI  - Polymerase chain reaction procedure to detect Trypanosoma cruzi in blood samples
      from chronic chagasic patients.
AB  - The feasibility of DNA amplification by the polymerase chain reaction for
      specific detection of Trypanosoma cruzi in human blood was investigated. We have
      used primers flanking a 220-bp fragment of highly repetitive elements, the E13
      element, in T. cruzi nuclear DNA. Only polymerase chain reaction products from
      blood samples of chronic chagasic patients showed several amplified fragments in
      1.6% agarose gels stained with ethidium bromide. Southern blot analysis
      demonstrated that the 220-bp amplified fragment is specific for T. cruzi DNA and
      very useful to detect the presence of the parasite in blood from chronic chagasic
      patients.

PMID- 9572025
TI  - Acalculous cholecystitis and septicemia caused by non-O1 Vibrio cholerae: first
      reported case and review of biliary infections with Vibrio cholerae.
AB  - The first case of septicemic acute acalculous cholecystitis caused by non-O1
      Vibrio cholerae is described in a healthy traveler, and biliary tract infections
      from V. cholerae are reviewed. Immediately after a vacation in Cancun, Mexico, a
      55-year-old man developed acute cholecystitis. Blood and bile cultures grew non
      O1 V. cholerae. At surgery, the gallbladder was acalculous, inflamed, distended,
      and nearly ruptured. Pathogenetic factors may have included diarrhea prophylaxis
      with bismuth subsalicylate, distension of the gallbladder from illness-induced
      fasting, and bacterial toxins in the gallbladder. The patient received i.v.
      cephapirin, followed by oral cephradine for a total of 10 days, and he made a
      quick and complete recovery. V. cholerae should be considered in the differential
      diagnosis of persons from endemic areas who present with cholecystitis or acute
      jaundice.

PMID- 9572026
TI  - Characterization of an isolate belonging to the newly described species
      Mycobacterium hassiacum.
AB  - The isolation, from a urine sample, of a rapidly growing acid-fast mycobacterium
      assigned to the thermophilic species Mycobacterium hassiacum led to further
      insight into present knowledge of this newly described organism. Already known
      phenotypic traits of M. hassiacum were extended and its susceptibility to
      additional antimicrobials was investigated. The high-performance liquid
      chromatography pattern of mycolic acids is, for the first time, presented. So
      far, no clinical relevance was proved for our isolate; likewise for the one which
      led to the species' original description.

PMID- 9572027
TI  - Evaluation of a disk diffusion method for determining susceptibility of
      Mycobacterium avium complex to clarithromycin.
AB  - We evaluated an agar disk diffusion method for determining the susceptibility of
      Mycobacterium avium complex to clarithromycin. Isolates were inoculated onto the
      surface of a Middlebrook 7H11 plate, followed by the application of a 15
      microgram clarithromycin disk. Zone sizes were read after 5-7 days of incubation.
      Zone sizes had a bimodal distribution; 40 isolates (10%) had no zone of
      inhibition, whereas the zone sizes for the remaining isolates ranged from 11 to
      60 mm. Most isolates (37/40) having no zone of inhibition came from patients who
      had been treated previously with clarithromycin. Fifty-one isolates were also
      tested for clarithromycin susceptibility using a microdilution broth method.
      Defining susceptibility as a zone size of > 10 mm, disk diffusion test results
      agreed with the results by the microdilution broth method for 50 of 51 (98%)
      isolates tested by both methods. Agar disk diffusion is a promising method for
      the determination of clarithromycin susceptibility testing for M. avium complex.

PMID- 9572028
TI  - Staphylococcus aureus and coagulase-negative staphylococci from blood stream
      infections: frequency of occurrence, antimicrobial susceptibility, and molecular
      (mecA) characterization of oxacillin resistance in the SCOPE program.
AB  - Staphylococci are major causes of nosocomial blood stream infection. The recently
      completed SCOPE Surveillance Program found that coagulase-negative staphylococci
      (CoNS) and Staphylococcus aureus were the first and second most common etiologic
      agents, respectively, causing nosocomial blood stream infection in the USA. The
      frequency of oxacillin resistance was 68% among 1553 strains of CoNS and 26%
      among 787 strains of S. aureus in this study. Extended susceptibility profiles
      were generated for a subset of 150 S. aureus and 300 CoNS against 16
      antimicrobial agents. Oxacillin-susceptible strains of both CoNS and S. aureus
      were uniformly susceptible to beta-lactam agents with the exception of ampicillin
      and penicillin. Oxacillin-susceptible S. aureus were also highly susceptible to
      the fluoroquinolones, aminoglycosides, and trimethoprim/sulfamethoxazole. The
      oxacillin-susceptible CoNS were less susceptible to these agents, and only
      glycopeptides were reliably active against oxacillin-resistant strains. PCR
      detection of the mecA gene was used to scrutinize current NCCLS interpretive
      breakpoint MICs for determining susceptibility or resistance to oxacillin. We
      found complete concordance between the presence or absence of mecA and the NCCLS
      oxacillin interpretive breakpoint categories for S. aureus. In contrast, the
      NCCLS breakpoints for oxacillin significantly underestimate the degree of true
      oxacillin resistance among CoNS. Using the presence of mecA as the reference
      standard, we detected 15.7% false susceptibility to oxacillin using a MIC
      susceptible breakpoint concentration of < or = 2 micrograms/mL. Lowering the
      oxacillin MIC breakpoint to < or = 0.25 microgram/mL for CoNS would greatly
      improve the accuracy of the MIC test performance. We found that both the current
      oxacillin disk test and the 30-microgram ceftizoxime disk test functioned quite
      well in predicting those strains of CoNS that contain mecA. These studies have
      demonstrated both a high level of antimicrobial resistance among nosocomial blood
      stream isolates of staphylococci as well as significant problems with the current
      NCCLS breakpoints for oxacillin when testing CoNS.

PMID- 9572029
TI  - Antimicrobial activity and spectrum investigation of eight broad-spectrum beta
      lactam drugs: a 1997 surveillance trial in 102 medical centers in the United
      States. Cefepime Study Group.
AB  - Because antimicrobial agents become less effective after the emergence of
      resistance mechanisms in clinically prevalent pathogens, physicians must utilize
      local, regional, and national antimicrobial susceptibility surveillance data to
      assist in choices of appropriate agents. An investigation of the spectrum and
      potency of eight broad-spectrum beta-lactam drugs (cefepime, cefotaxime,
      ceftazidime, ceftriaxone, imipenem, piperacillin with or without tazobactam, and
      ticarcillin/clavulanic acid) was performed using a common protocol and method
      (Etest; AB BIODISK, Solna, Sweden) in 102 clinical microbiology laboratories in
      the United States. A total of 9777 strains of Gram-negative bacilli were tested
      from late 1996 through April 1997. Quality assurance measures using three control
      strains observed quality control failures in 13 laboratories (usually
      ticarcillin/clavulanic acid or piperacillin), but only 2% of results required
      deletion. A total of 33.4% of Enterobacter spp. (1977 strains) were either
      resistant or intermediately susceptible to ceftazidime. Only imipenem (99.6%
      susceptible) and cefepime (99.1%) remained highly active against strains of
      Enterobacter, as well as Citrobacter freundii, indole-positive Proteae, and
      Serratia spp. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae
      were detected at rates of 10.3% and 23.8%, respectively. Although these were
      participant-selected strains, only imipenem and cefepime had broad-spectrum
      coverage (> or = 97.1%) against these extended-spectrum beta-lactamase
      phenotypes. A dominant number of these extended-spectrum beta-lactamase
      phenotypes were reported from medical centers in the Northeast, but a nationwide
      distribution was observed. Among the nonenteric Gram-negative bacilli (4057
      strains), the rank order of susceptibility (percent inhibited at published
      breakpoint concentrations) was: imipenem (86.1%) > piperacillin/tazobactam
      (80.1%) > cefepime (77.1%) > ceftazidime = piperacillin (74.9%) >
      ticarcillin/clavulanic acid (61.6%) > cefotaxime (18.2%) > ceftriaxone (12.9%).
      The cephalosporins, cefepime and ceftazidime, had rates of resistance for the
      3005 Pseudomonas aeruginosa isolates of 10.1% and 14.4%, respectively. For all
      Gram-negative strains tested, only two contemporary beta-lactam antimicrobials
      exhibited > 90% inhibition of strains, imipenem at 93.6% and cefepime at 90.2%.
      These drugs were superior to the other tested compounds (48.8-84.3%).
      Ticarcillin/clavulanic acid had the narrowest spectrum of activity (48.8% of
      isolates susceptible). These results indicate that carbapenems and a new fourth
      generation cephalosporin, cefepime, possess usable in vitro potencies against
      current clinical strains of Gram-negative bacilli, many of which harbored
      resistance to other antimicrobial agents.

PMID- 9572030
TI  - Pichia ohmeri fungemia.
AB  - A patient with a history of diabetes, coronary artery disease, stroke, previous
      renal transplantation, and multiple hospital admissions for recurrent
      pancreatitis was transferred to the hospital from a chronic care facility because
      of fever and severe epigastric discomfort. At the time of admission, she was
      receiving hyperalimentation through a central venous TPN catheter. Multiple blood
      cultures obtained on the first and second hospital days yielded pure cultures of
      the yeast, Pichia ohmeri. The patient developed acute renal failure, and despite
      high-dose amphotericin B therapy, ultimately expired.

PMID- 9572031
TI  - Management of hepatitis C.
AB  - Chronic hepatitis C is a major health care problem throughout the world. The
      disease may progress to cirrhosis, with complications such as hepatocellular
      carcinoma. The usual primary goal of therapy is viral eradication, as patients
      with long-term remission are generally regarded as unlikely to develop cirrhosis
      or hepatocellular carcinoma. Another primary goal should be the reduction in
      liver fibrosis progression. Interferon-alpha (IFN-alpha) is the only drug
      approved for the treatment of hepatitis C in Europe and North America. Its
      effectiveness appears to be related to dose and duration of therapy. The best
      efficacy/risk ratio seems to be in favour of 3 million units (MU) IFN-alpha three
      times per week on a 12-month schedule. With this regimen, a sustained alanine
      aminotransferase (ALT) response is achieved in nearly 35% of patients. Ribavirin
      has emerged as potentially the second most effective drug. While it appears
      unsatisfactory when given alone, it seems much more effective in combination with
      IFN. Combining them seems to exert a synergistic effect between the two drugs and
      sustained remission might be achieved in nearly 50% of patients with combination
      therapy. Controversy persists concerning the long-term benefit of therapy in
      transient responders and non-responders. It is possible that IFN therapy, in
      comparison to natural history, might reduce liver fibrosis progression and
      prevent hepatocellular carcinoma, even in non-responders, and have greater
      efficacy if used in long-term treatment. Whatever the treatment schedule,
      prolonged viral eradication may not be achieved in all patients and new drugs
      should be sought to improve the results of therapy.

PMID- 9572032
TI  - Composition of peripheral blood lymphocyte populations during different stages of
      chronic infection with hepatitis B virus.
AB  - To characterize the immunological populations associated with different stages of
      chronic infection with hepatitis B virus (HBV), we performed flow cytometric
      analyses on the peripheral blood leucocytes of 29 patients with various forms of
      chronic hepatitis B. The clinical spectrum of the patients ranged from
      asymptomatic infections, in the presence of high virus production, to
      intermittent or recurrent exacerbations of liver injury alternating with
      relatively normal liver function. Patients with partial resolution of disease who
      experienced an initial acute flare followed by prolonged seroconversion showed
      decreased percentages of CD3+ cells during the seroconversion phase when levels
      of serum alanine transferase (ALT) had normalized. These CD3+ cells were
      predominantly CD4+ cells bearing the alpha beta+ T-cell receptor (TCR). In
      addition, we saw an increase in CD4+ and CD8+ cells bearing the gamma delta TCR
      in those patients who had seroconverted. No significant differences were seen
      between any of the groups with respect to percentage of cells with a naive
      (CD45RA) or memory (CD45RO) phenotype, or of cells displaying the activation
      markers CD38, HLA-DR or CD57. Longitudinal analyses of 15 patients failed to show
      any consistent pattern of changes in the immunophenotypic profile during acute
      flares and their resolution. Our results indicate that the turnover of
      circulating T lymphocytes during the apparent quiescent phase of chronic
      infections is higher than that during acute exacerbations, suggesting an active
      immunosurveillance role of T-cell subpopulations in maintaining low virus levels
      during seroconversion.

PMID- 9572033
TI  - Identification of novel sequences at the 5' terminus of the hepatitis C virus
      genome.
AB  - To permit accurate identification of the 5' end of the HCV genome, we used RNA
      ligase-mediated rapid amplification of cDNA ends (RLM-RACE) where an RNA molecule
      of known sequence (transcribed in vitro from a cDNA template) was ligated to RNA
      purified from a hepatitis C virus (HCV)-infected liver sample. After ligation,
      the product was amplified by nested polymerase chain reaction (PCR) and amplicons
      that were equal to or greater in size than those predicted from the recognized 5'
      terminus of the HCV genome were cloned into pBluescriptKS. Twelve clones were
      sequenced, including three that were identical and contained an additional eight
      nucleotides, namely CCCCCCCA. Thus, the HCV 5' untranslated region (UTR) is now
      recognized as comprising 349 nucleotides, although it is possible to speculate
      that these additional nucleotides are part of a second, as yet undetected, stem
      loop at the extreme 5' terminus of the genome.

PMID- 9572034
TI  - In subjects with antibody to hepatitis C virus a high serum level of interleukin
      2 soluble receptor suggests activity of liver disease.
AB  - The hepatitis C virus (HCV) is an RNA virus without apparent cytopathic effects,
      and hepatocellular damage in chronic infection is generally believed to be immune
      mediated by cytotoxic T lymphocytes. Activated T cells release the soluble form
      of the interleukin-2 (IL-2) receptor (sIL-2R) and its concentration is correlated
      with the degree of lymphocyte activation. We measured sIL-2R in 69 subjects: 24
      healthy repeat blood donors (group I), 17 HCV carriers without liver damage
      (group II) and 28 patients with HCV-related chronic active hepatitis (group III).
      There was no significant difference between sIL-2R levels in patients of group I
      (36.5 +/- 14.6 U ml-1) and group II (46.8 +/- 17.4 U ml-1), and the levels for
      both of these groups were significantly lower than those observed in the patients
      with active HCV, group III (176.9 +/- 59.5 U ml-1). Hence, among HCV-infected
      subjects (HCV RNA positive) with persistently normal alanine aminotransferase
      (ALT) levels, the plasma levels of sIL-2R are normal, but, in patients (HCV RNA
      positive) with HCV-related chronic active hepatitis there are increased plasma
      levels of sIL-2R. We conclude that in HCV infection high levels of sIL-2R are
      related to activity of the disease rather than to virus replication. In patients
      with HCV-related chronic liver disease, the sIL-2R concentration may be a useful
      marker of disease activity.

PMID- 9572035
TI  - Statistical models for predicting a beneficial response to interferon-alpha in
      patients with chronic hepatitis B.
AB  - Therapy with interferon-alpha has been reported to induce remissions in 35% of
      patients with chronic hepatitis B. The ability to identify patients likely to
      respond would be helpful in making recommendations for treatment. In this
      statistical analysis we included 82 patients with chronic hepatitis B who
      received interferon-alpha in clinical trials at the National Institutes of Health
      between 1984 and 1991. A response was defined as the loss of hepatitis B virus
      (HBV) DNA and hepatitis B e antigen (HBeAg) within 1 year of therapy. Multiple
      clinical parameters measured at pretreatment (month 0) and after the first month
      (month 1) of therapy were selected by stepwise regression to support the
      development of the prognostic models: the two-stage logistic regression model and
      a neural network that utilized higher-order non-linear interactions between
      variables. Among the 82 patients, 24 (29%) were responders. The two-stage
      logistic model using pretreatment variables: sex, hepatic fibrosis and alanine
      aminotransferase (ALT) levels correctly identified 61% of responders and 76% of
      non-responders. When HBV DNA at month 1 along with sex, initial ALT and fibrosis
      was included, the resultant model correctly identified 69% of responders and 77%
      of non-responders. The neural network, by incorporating interactions between
      variables, correctly identified 77% and 86% of responders, and 87% and 92% of non
      responders, using pretreatment factors alone and the combination of pretreatment
      and month 1 factors respectively. Hence, the neural network was more accurate
      than the simple logistic regression model in predicting a response to interferon
      alpha in chronic hepatitis B. The universality of these models needs to be
      further verified.

PMID- 9572036
TI  - Prospective virological follow-up of hepatitis C infection in a haemodialysis
      unit.
AB  - Hepatitis C virus (HCV) is of major concern in the management of patients on
      maintenance haemodialysis. Many studies have reported a high prevalence of HCV
      infection in dialysis centres. The objective of our study was first, to perform a
      prospective follow-up of the evolution of HCV infection in a haemodialysis
      centre, and second, to assess the rate of viral clearance in patients on
      dialysis. For this, genotypes, HCV antibodies (anti-HCV) and HCV RNA were
      evaluated initially and 9 months later. HCV RNA quantification was also
      performed. Of 136 patients, 62 (45.6%) were anti-HCV positive by third-generation
      enzyme immunoassay (EIA 3) in the first survey and 64 of 136 (47.1%) were anti
      HCV positive by EIA 3 in the second survey. The rate of new HCV infection,
      estimated from the two seroconversions between the surveys, was 1.9% per year.
      One of the two patients was initially HCV RNA positive, with a titre of 0.6 x
      10(6) eq ml-1. The viral load measured in the dialysis patients was low and does
      not seem to be influenced by dialysis. No significant difference was observed in
      viral load between the two periods nor were there any gender-related differences
      in viral load. In conclusion, detection of antibodies to HCV, together with HCV
      RNA, seems to be relevant in haemodialysis patients, but this strategy is not
      suitable for use in all haemodialysis centres because of its high cost.

PMID- 9572038
TI  - Medical practices regarding hepatitis C virus infection in Europe.
AB  - Six hundred and ninety-three European Association for the Study of the Liver
      (EASL) members, belonging to one of the 15 European Union (EU) member-states,
      were surveyed, through a standardized 45-item questionnaire, on their medical
      practices regarding hepatitis C virus (HCV) infection. The response rate was 45%,
      roughly similar in all the countries concerned. Responders were classified into
      three groups according to their geographical origin: North, Centre and South. A
      consensus existed with regard to the necessity of HCV screening in well-defined
      situations, such as history of blood transfusion, haemodialysis, haemophilia or
      intravenous drug addiction (90% of positive answers) while opinions substantially
      differed for vertical and nosocomial transmission of HCV. For the prevention of
      sexual and vertical transmission, opinions differed greatly: 22% were in favour
      of barrier methods for HCV-positive subjects while 34% were against; 49% allowed
      breast-feeding for babies born to HCV-positive mothers while 14% were against.
      Conversely, there was relative homogeneity in the issue of domestic prevention
      (70% in favour of precautions). Algorithms for prescription of virological tests
      were inhomogeneous (recombinant immunoblot assay was used by 60%; polymerase
      chain reaction was requested by 77% when alanine amino-transferase (ALT) was
      elevated vs 89% when normal): medical evaluation varied according to ALT values:
      liver biopsy and liver ultrasonography were carried out in 90 and 91% vs 40 and
      70% for increased and normal ALT, respectively. Thirty per cent of respondents
      advised patients to stop alcohol consumption and 60% advised moderation. Two
      thirds of the responders did not take into account histological severity and
      virological parameters before initiating antiviral therapy. Eighty per cent of
      the participants claimed that they administered interferon (IFN) for 12 months.
      For most of the items studied, there was a large variation, not only between the
      three groups, but also within each group. Ninety-two per cent of the responders
      claimed that they were well trained on HCV but they were rather critical of the
      quality of the information diffused (satisfaction rate: 45%). Altogether, our
      survey demonstrates that preventive and medical practices towards HCV are not
      homogeneous throughout the EU; this suggests the need for a European consensus
      conference in this regard.

PMID- 9572037
TI  - Hepatitis G virus infection in hepatitis C virus-positive patients co-infected or
      not with hepatitis B virus and/or human immunodeficiency virus.
AB  - This was a retrospective study to evaluate the prevalence and impact of hepatitis
      G virus (HGV) infection in hepatitis C virus (HCV)-positive drug addicts,
      according to the serological status of hepatitis B virus (HBV) and human
      immunodeficiency virus (HIV) coinfection. Two hundred and thirty-five randomly
      selected intravenous drug addicted patients (147 French, 88 Italian) were
      studied. All patients were positive for antibodies to HCV (anti-HCV). HGV RNA
      positivity was measured by reverse transcriptase-polymerase chain reaction (RT
      PCR). Comparisons of HCV RNA positivity rate, and biological and
      histopathological variables, were made between HGV RNA-positive and negative
      patients, according to their HBV and HIV status. HGV prevalence was around 30% in
      both French and Italian groups. No clear association between HGV infection and a
      particular HCV genotype was observed. The rate of HCV RNA positivity did not
      differ between HGV-positive and HGV-negative patients after stratification for
      hepatitis B surface antigen (HBsAg) and HIV positivity. Histological severity of
      the underlying chronic hepatitis did not differ according to the HGV status;
      however, in HIV-positive HBsAg-negative patients, the hepatitis activity was
      moderately increased in HGV-positive patients. A striking negative influence of
      HBsAg positivity on HCV replication was observed in HIV-negative patients; an HCV
      RNA-positive rate of 25% was found in HBsAg-positive patients vs 86% in HBsAg
      negative patients; similar significant results were observed in HIV-positive
      patients, although to a lesser extent. The underlying chronic hepatitis was
      significantly more severe in HBsAg-positive than in HBsAg-negative HIV-negative
      patients. Hence, HGV infection is highly prevalent in anti-HCV positive drug
      addicts but the co-infection with HCV does not seem to influence HCV replication
      nor to worsen the underlying chronic hepatitis, in HIV-negative patients at
      least. Reciprocal influence between HBV, HCV and HIV appears rather complex,
      HBsAg carriage seeming to exert per se a negative effect on HCV replication,
      particularly in HIV-negative patients, suggesting that interactions between
      hepatitis viruses should always be analysed in the light of HIV status.

PMID- 9572039
TI  - Antigenic characteristics of polypeptides of Coxiella burnetii isolates.
AB  - Eighteen Coxiella burnetii strains from a variety of clinical and geographical
      sources were screened for antigenic variation of polypeptides by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with Coomassie
      brilliant blue (CBB) staining or immunoblotting. These polypeptide profiles
      showed the greatest variability in the region from 33 to 8.1 kDa. Such
      differences in the antigenicity of the polypeptides were also recognized by
      immunoblotting with 15 various mouse anti-C. burnetii antisera. In addition, we
      detected a polypeptide at about 28 kDa which was immunodominant in strains from
      human cases of acute Q fever, milk and ticks but not immunogenic in strains from
      human cases of chronic Q fever. These findings suggest that this polypeptide is a
      marker to distinguish between acute and chronic strains.

PMID- 9572040
TI  - Partial analysis of the flagellar antigenic determinant recognized by a
      monoclonal antibody to Clostridium tyrobutyricum.
AB  - In order to count Clostridium tyrobutyricum spores in milk after membrane
      filtration, murine 21E7-B12 monoclonal antibody was produced. Elution of the
      monoclonal antibody from this antigen, the flagellar filament protein, by
      carbohydrate ligands was used to study the epitope structure. A competitive
      elution of an anti-dextran monoclonal antibody by carbohydrate ligands served as
      a control in order to validate the immunological tool applied to flagellin
      epitope study. The carbohydrate moiety of flagellin contained D-glucose and N
      acetyl-glucosamine in a molar ration of 11:1 as determined by gas-liquid
      chromatography and 2 low-abundancy unidentified compounds. In ELISA, D-glucose
      and N-acetyl-glucosamine did not dissociate the antibody-flagellin complex
      contrary to maltose, maltotriose, maltotetraose and maltopentaose. The efficiency
      of elution increased from the dimer to the pentamer and became nil for
      maltohexaose and maltoheptaose. The fact that the hexamer and heptamer could not
      react with the 21E7-B12 monoclonal antibody could be explained by a drastic
      conformational change. The over-all stretched maltopentaose switch to a helical
      shaped maltoheptaose which could not fit the 21E7-B12 monoclonal antibody antigen
      combining site. Thus, flagellin epitope may contain alpha (1-->4) linked glucose
      residues plus either N-actyl-glucosamine or an unidentified compound that
      maintain it in an extended shape.

PMID- 9572041
TI  - Enhancement of human immunodeficiency virus type 1 (HIV-1) infection via
      increased membrane fluidity by a cationic polymer.
AB  - Cationic polymers are known to have potent activity against bacteria, but their
      effects on viral activity have been little studied. We investigated the effect of
      one such polymer, polyethyleneimine (PEI), on HIV-1 infection. Although virus
      cell binding was significantly inhibited by PEI, HIV-1 infection in human T-cell
      lines such as MT-4 and MOLT-4 was accelerated conversely when the drug treatment
      was carried out, after the virus had attached to the cells or PEI was
      simultaneously added to the virus and cell culture system. This paradoxical
      effect of PEI on HIV-1 infection was examined using HIV-1 chronically infected
      cells (MOLT-4/HIV-1). Dissociation of the glycoprotein gp120 (as revealed by
      exposure of transmembrane protein gp41) from MOLT-4/HIV-1 cells and the resultant
      fusion of these cells was shown to be induced by the addition of PEI.
      Accordingly, it was suggested that the binding inhibition of HIV-1 to CD4
      positive cells by PEI was due to the shedding of gp120 from HIV-1 particles, and
      this PEI rather promoted membrane fusion between the virus and cells leading to
      the enhancement of HIV-1 infection. Similarly, dissociation of gp120 from MOLT
      4/HIV-1 was also induced by sCD4. The effect of these reagents on changes in
      membrane fluidity was evaluated by polarization (p) measurements, and it was
      observed that the acceleration of membrane fluidity occurred only in the PEI
      system. Therefore, it is likely that PEI accelerates HIV-1 infection by
      facilitating virus entry into the host cells through an increase in membrane
      fluidity.

PMID- 9572042
TI  - Elevated serum levels of the soluble form of gp130, the IL-6 signal transducer,
      in HTLV-1 infection and no involvement of alternative splicing for its
      generation.
AB  - By using an ELISA, increased levels of the soluble form (sgp130) of gp130, the IL
      6 signal transducer, were detected in the sera of various HTLV-1-associated
      conditions (HC, ATL, HAM) as compared to normal healthy individuals. Sgp130
      levels seemed to be correlated with disease severity. The 94 KD of sgp130 was
      specifically precipitated in the sera of HTLV-1-infected patients as revealed by
      Western blot analysis. A reverse transcriptase (RT)-polymerase chain reaction
      (PCR) method was used to detect the message for transmembrane (TM) lacking gp130
      in mRNA isolated from peripheral blood mononuclear cells (PBMCs) of patients
      infected with or without HTLV-1 and those of various hematopoietic cell lines.
      Two PCR products, 648 and 507 bp were observed in the PBMCs from HTLV-1-infected
      patients. But the 507 by PCR product was not detected in the PBMCs from normal
      healthy individuals and HTLV-1-positive cell lines although the 648 bp product
      was equally expressed. A nucleotide sequence analysis of the 507 bp fragment
      showed deletion of the 141 bp at the region spanning from nucleotide 1702 (G) to
      1842 (T) of the 648 bp product that matched completely with a conventional gp130
      molecule. This deleted region was located upstream of the transmembrane (TM)
      domain, but not within the TM region itself. However, no frame shift was
      observed. These results indicate that the generation of sgp130 may not be due to
      an alternative splicing mechanism.

PMID- 9572043
TI  - Liver-associated natural killer activity in cirrhotic rats.
AB  - An impaired host defense mechanism is well known in patients with liver cirrhosis
      (LC). Using a sinusoidal lavage method, lymphocytes were obtained from LC rats
      that were administered thioacetamide, and natural killer (NK) activity was
      measured by 51Cr-release assay. The NK cell count was measured by flow cytometric
      analysis using monoclonal antibody (Mab) 3.2.3 and/or CD 3-8+ as markers for NK
      cells, and by immunohistochemical staining using Mab 3.2.3. Furthermore,
      interferon (IFN) alpha was administered to LC rats and the subsequent changes in
      hepatic NK activity and NK cell count were observed. In the large granular
      lymphocyte (LGL)-rich fraction (Fr.1, LGLs: 60-90%), the NK activity was
      significantly lower in the LC rats (40.0 +/- 3.8%) compared to that in the
      control rats (48.4 +/- 4.3%) (P < 0.005). In addition, the number of NK cells in
      the liver tissues of the LC rats was significantly lower compared to that in the
      liver tissues of the control rats by morphometric analysis (P < 0.05). For LC
      rats, NK activity of the Fr.1 24 hr after IFN alpha administration (5 x 10(4)
      IU/100 g body weight) increased significantly (P < 0.005). Hepatic NK activity
      and NK cell count were reduced in the LC rats, and recovered following IFN alpha
      administration. The results obtained in this study may give clues to better
      understanding the impaired host defense mechanism in LC patients.

PMID- 9572044
TI  - Protective effect of Japanese green tea extract on gnotobiotic mice infected with
      an Escherichia coli O157:H7 strain.
AB  - We examined the effect of Japanese green tea extract (JGTE) on enterohemorrhagic
      Escherichia coli (EHEC) O157:H7 infection in a gnotobiotic mouse model.
      Gnotobiotic mice inoculated with an EHEC strain developed neurologic and systemic
      symptoms, usually culminating in death. In contrast, none of mice receiving
      dietary JGTE showed clinical signs or death. This report describes the effect of
      JGTE, which includes the inhibition of bacterial growth in vivo. The Shiga-like
      toxin (SLT) level in the feces of the JGTE diet group was significantly lower
      than that of the control group.

PMID- 9572045
TI  - Sequence analysis of the actA gene of Listeria monocytogenes isolated from human.
AB  - The region encoding proline-rich units of actA genes was amplified from 24
      strains of Listeria monocytogenes using polymerase chain reaction (PCR). PCR
      products of 13 strains showed the expected size of 623 bp, whereas those of 11
      strains showed a short size of 518 bp. The shortening of these PCR products
      resulted from the deletion of one proline-rich unit. These results indicate that
      ActA proteins are divided into at least two different types which are unrelated
      to bacterial serotypes.

PMID- 9572046
TI  - Cloning and characterization of the genomic RNA sequence of the mumps virus
      strain associated with a high incidence of aseptic meningitis.
AB  - cDNA clones of the mumps virus wild-type strain, associated with a high incidence
      of aseptic meningitis (ODATE-1 strain), were isolated and analyzed from genomic
      nucleotide position 22 to 8520 containing the NP, P, M, F, SH and HN protein
      coding region. The ODATE-1 strain exhibited a RFLP profile identical to that of
      the Urabe vaccine strain in spite of the fact that the virus was isolated from
      non-vaccinated cases. However, a comparison of nucleotide and amino acid
      sequences among the ODATE-1 strain, Urabe strain and Miyahara strain revealed
      that the ODATE-1 strain was not related to the Urabe strain.

PMID- 9572047
TI  - Effect of acidic fibroblast growth factor (aFGF) on phagocytosis in mouse
      peritoneal macrophages.
AB  - The effects of acidic fibroblast growth factor (aFGF) on phagocytosis in
      peritoneal macrophages from thioglycollate-elicited mice were examined using flow
      cytometry. aFGF enhanced phagocytosis of fluorescein isothiocyanate-labeled latex
      particles in a dose-dependent manner. Basic fibroblast growth factor (bFGF) also
      enhanced phagocytosis. This study suggests that aFGF can modulate an important
      activity of macrophages.

PMID- 9572048
TI  - Diagnostic evaluation of a synthetic peptide derived from a novel antigen B
      subunit as related to other available peptides and native antigens used for
      serology of cystic hydatidosis.
AB  - A synthetic peptide (GU4) derived from an antigen B (AgB) subunit was
      serologically compared with crude antigen (HCFA); immunopurified AgB and antigen
      5 (Ag5), and two other synthetic peptides, for diagnosis of human cystic
      hydatidosis. GU4 was derived from the sequence of AgB/2, the novel AgB subunit
      described by us. The other two peptides: 65 (AgB mimotope) and 89-122 (Ag5
      mimotope), were described by others. Antigens B and 5 showed higher diagnostic
      sensitivity than corresponding peptides. All sera reacting with peptides 89-122
      and GU4 also reacted with 65. The latter provided three to four times higher
      sensitivity than the former two peptides, but 30% lower specificity. The
      diagnostic efficiency of AgB (82%) was higher than those of Ag5 (74%) and HCFA
      (71%). Interestingly, 89-122 only reacted with hydatid sera, some of which did
      not react with AgB. Considering positive those reacting with 89-122 or AgB,
      sensitivity increases from 77% (with AgB) to 82% (combined), while specificity is
      the same as with AgB (86%). Our results suggest that hydatid serology may be
      improved by: a) combining several defined antigens (including synthetic
      peptides), b) design of new E. granulosus-specific mimotopes, which react with
      the false negative sera (16/90; 18%).

PMID- 9572049
TI  - Immune responses to Plasmodium falciparum antigens during a malaria vaccine trial
      in Tanzanian children.
AB  - Among Tanzanian children living in an area of intense and perennial malaria
      transmission, prevalence of naturally acquired IgG antibodies that recognize
      SPf66, NANP, p190 and a 19 kDa fragment of the merozoite surface protein-1 (MSP
      1) is high and increases with age. This possibly reflects the high level of
      natural exposure of the children to P. falciparum. The prevalences of IgG
      antibodies that recognize the three putative merozoite derived sequences
      contained in the malaria vaccine SPf66 (83.1, 55.1 and 35.1) is low but also show
      some age dependence. Three doses of the SPf66 vaccine induce a strong IgG
      antibody response against both the SPf66 construct, NANP and the three individual
      peptides. Vaccination with SPf66 did not result in an increase of anti19 kDa
      fragment antibodies. This reflects the specificity of the humoral immune response
      induced by the SPf66 construct. Among vaccinated children, antibody titres
      against SPf66 decreased over time following the third dose. However, 18 months
      after the third dose, SPf66 recipients still had significantly higher IgG titres
      and stimulation indices of peripheral blood mononuclear cells (PBMC) than placebo
      recipients. Within the vaccine group, there is a trend for increasing anti-SPf66
      IgG titre to be associated with decreasing risk of clinical malaria but this was
      not statistically significant. Results also show the difficulties of establishing
      whether antibody responses are related to protection in field trials in endemic
      areas.

PMID- 9572050
TI  - Characterization of Neospora caninum iscom antigens using monoclonal antibodies.
AB  - Neospora caninum is a cyst-forming coccidian parasite which in cattle can cause
      abortion and birth of feeble calves. For the serological diagnosis of
      neosporosis, antibodies directed to the parasite can be demonstrated by ELISA,
      utilizing N. caninum proteins incorporated into iscoms (immunostimulating
      complexes) as antigen. Electrophoretic and immunoblotting studies had earlier
      revealed that N. caninum iscoms contained a restricted number of proteins
      compared with soluble parasite extracts, but the cellular origin of the
      incorporated proteins has not yet been determined. In the present study,
      monoclonal antibodies were raised against N. caninum iscoms. Six of these, named
      Ncmab-4, 7, 10, 13, 17 and 24, were used to characterize the N. caninum iscom
      antigen. The nature of the reactive epitopes and their localization within N.
      caninum tachyzoites were determined by means of immunological methods, including
      immunoblot, IFAT and immunogold electron microscopy. The apparent molecular
      weights of the dominant iscom antigens were found to be 18, 30, 32, 41 and 61
      kDa. While the 61 kDa antigen was located intracellularly, the others were found
      on the parasite surface as well as within distinct intracellular compartments.

PMID- 9572051
TI  - In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary
      alveolar echinococcosis.
AB  - Using an experimental model of hepatic Echinococcus multilocularis infection in
      C57BL/6J mice, intraperitoneal administration of 0.8 microgram of recombinant IL
      12 to mice with an established infection was shown to reduce the parasite burden
      as soon as two weeks after the end of treatment. At that time, in vitro
      Echinococcus multilocularis-induced spleen T cell proliferative responses as well
      as IFN-gamma and IL-5 production were higher in IL-12 treated mice than in
      untreated mice. Administration of 0.8 microgram of IL-12 at the time of infection
      was shown to be without effect on the parasite establishment. However, this
      treatment greatly inhibited the subsequent metacestode development. Indeed, ten
      weeks after infection, it induced a complete healing in 37.5% of mice. At that
      time, the development of metastases was inhibited in 68.75% of IL-12-treated
      mice. This reduction of parasite burden was mainly associated with a strong
      proliferation of spleen cells to E. multilocularis antigen and with a high IFN
      gamma production. Altogether, our results show that IL-12 is of crucial
      importance in inhibiting the larval growth after the metacestode establishment in
      the liver and suggest that this cytokine could be of potential value in the
      treatment of human alveolar echinococcosis.

PMID- 9572052
TI  - Eosinophil-mediated killing of Haemonchus contortus larvae: effect of eosinophil
      activation and role of antibody, complement and interleukin-5.
AB  - Eosinophils have previously been shown to accumulate around the tissue invasive
      (L3) stage of sheep gastrointestinal parasites in vivo. In this study,
      eosinophils obtained from mammary washes of sheep, were shown to immobilize and
      kill H. contortus larvae in vitro in the presence of antibody specific against a
      defined L3 surface antigen. Eosinophils obtained from sheep primed by repeated
      infusion of H. contortus larvae were more effective than eosinophils obtained
      after a single infusion of parasite extract in Fasciola hepatica infected ewes
      suggesting the former were activated in vivo. The level of larval immobilization
      in the presence of antibody was significantly increased when complement was added
      to cultures containing activated eosinophils. The addition of interleukin-5 to
      larval cultures containing antibody and complement resulted in a significant
      increase in larval immobilization with unactivated eosinophils suggesting that
      eosinophil effector function is enhanced following priming with this cytokine.
      Ultrastructural analysis of the eosinophil/larvae interaction at 6 h of
      incubation revealed degranulation of adhering eosinophils onto the surface of
      larvae. By 24 h of incubation, many larvae showed signs of damage and most
      eosinophils had degenerated. These results suggest that eosinophil-mediated
      killing may be an effector mechanism for the elimination of L3 H. contortus
      larvae in immune sheep.

PMID- 9572053
TI  - Blood substitute receives FDA approval for veterinary use.

PMID- 9572054
TI  - Triplex DNA as a novel diagnostic tool.

PMID- 9572055
TI  - The commercialization of human genetics: profits and problems.
AB  - Private-sector funding is becoming increasingly important to genetic scientists
      and clinicians, and the number of academic-industry collaborations is growing
      rapidly. Furthermore, genetics has become an important tool for the healthcare
      industry, as the genomes of humans and other organisms are mined for new
      diagnostic tests and drug leads. Potentially, this is a win-win situation:
      academic research gets a funding boost; industry benefits from academic research;
      and humankind benefits from the products of these liaisons. But these benefits do
      not come without cost. This article explores these costs and examines whether the
      commercialization of academic research is compromising academic freedom, progress
      in clinical research, and our attitudes to normal good health.

PMID- 9572056
TI  - Molecular pathogenesis of sporadic and familial forms of Alzheimer's disease.
AB  - Our understanding of the pathogenesis of Alzheimer's disease (AD) comes primarily
      from the study of rare inherited forms of the disease. Mutations that cause
      familial AD appear to act by a common mechanism: that of increasing production of
      A beta 42/43, one of the family of A beta peptides deposited in senile plaques.
      However, increased A beta 42/43 production has not been demonstrated to occur in
      most cases of sporadic AD, suggesting that genetic and environmental factors
      acting at other stages of the disease process can modify the risk for disease.
      Such factors most likely include those affecting A beta aggregation or clearance,
      the inflammatory response, cerebrovascular disease, or susceptibility of neurons
      to injury. Identifying these factors will lead to a better understanding of the
      etiology of the disease and provide additional targets for therapeutic
      intervention.

PMID- 9572057
TI  - Biology and potential strategies for the treatment of GM2 gangliosidoses.
AB  - The GM2 gangliosidoses are a group of heritable neurodegenerative disorders
      caused by excessive accumulation of the ganglioside GM2 owing to deficiency in
      beta-hexosaminidase activity. Tay-Sachs and Sandhoff diseases have similar
      clinical phenotypes resulting from a deficiency in human hexosaminidase alpha and
      beta subunits, respectively. The lack of treatment for GM2 gangliosidoses
      stimulated interest in developing animal models to understand the molecular
      mechanisms underlying the various forms of this disease and to test new potential
      therapies. In this review, we discuss the molecular biology of GM2 gangliosidoses
      and the different strategies that have been tested in animal models for the
      treatment of this genetic disorder, including gene transfer and cell engraftment
      of neural stem cells engineered to express the hexosaminidase isoenzymes.

PMID- 9572058
TI  - Vaccines against Chlamydia: approaches and progress.
AB  - Infections of the eye and genital tract with the bacterium Chlamydia trachomatis
      are a major cause of morbidity worldwide and are costly to treat. Development of
      a vaccine capable of protecting against infection or severe disease presents
      special challenges but would be the most effective long-term option for control
      of chlamydial disease. Progress has been made in understanding protective and
      pathological immune mechanisms in these infections, and a number of potential
      vaccine candidates have been developed.

PMID- 9572059
TI  - New horizons for therapy based on the boron neutron capture reaction.
AB  - Boron neutron capture therapy (BNCT) is currently undergoing clinical trials in
      the USA, Japan and The Netherlands with patients afflicted with deadly brain
      cancer (glioblastoma multiforme) or melanoma. This therapy relies on a binary
      process in which the capture of a slow neutron by a 10B nucleus leads to an
      energetic nuclear fission reaction, with the formation of 7Li3+ and 4He2+ and
      accompanied by about 2.4 MeV of energy. The fleeting 7Li3+ and 4He2+ travel a
      distance of only about the diameter of one cell, and they are deadly to any cell
      in which they have been produced. Research in progress is concerned with the
      development of advanced boron agents and neutron sources, other than nuclear
      reactors, for the treatment of a variety of cancer types using novel 10B delivery
      methods. Non-malignant diseases such as rheumatoid arthritis offer additional
      opportunities for BNCT. The entire BNCT area awaits commercialization.

PMID- 9572060
TI  - Redundant down-regulation pathways for p53.
AB  - The aim of this review is to underline the redundancy of down-regulation pathways
      for p53, at the light of the two more important degradative systems: calpains and
      ubiquitin-dependent pathways. The MDM2 feed-back loop is also illustrated, as
      well as the phosphorylative/dephosphorylative regulation of the latent and active
      p53 isoforms. The mechanisms prolonging p53 half life, following irradiation, are
      also discussed.

PMID- 9572061
TI  - Potential therapeutic value of drugs inhibiting semicarbazide-sensitive amine
      oxidase: vascular cytoprotection in diabetes mellitus.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is a copper-containing enzyme found
      in large amounts in blood plasma and in vascular smooth muscle. The catalytic
      activity of this enzyme is elevated in diabetes mellitus and some substrates,
      such as aminoacetone and methylamine also occur in increased amounts in this
      disease. After deamination by SSAO highly angiotoxic products are formed,
      methylglyoxal and formaldehyde, respectively. Moreover, hydrogen peroxide is also
      formed as a side-product. These products arising from SSAO-catalysed reactions
      may partially explain late-diabetic damages in the kidneys, eyes and peripheral
      nerves, as well as other cardiovascular disorders. It is therefore proposed that
      inhibition of SSAO may decrease the formation of these cytotoxic products and
      therefore prevent or slow the development of late-diabetic complications.

PMID- 9572062
TI  - AUC and cmax are not sufficient to prove bioequivalence.

PMID- 9572063
TI  - Human albumin enriched St. Thomas Hospital cardioplegic solution increases
      reperfusion injury in isolated perfused rat hearts.
AB  - In open heart surgery it is very important to protect the heart during the
      ischaemic period in terms of mortality and morbidity. Many different cardioplegic
      solutions are in clinical use without being tested experimentally. In this study
      we intended to investigate the effects of albumin addition to St. Thomas Hospital
      cardioplegic solution on cardiac protection to ischaemia. Rat hearts were
      isolated and perfused in Langendorff apparatus (n = 6 for each group). After the
      stabilisation period, the hearts in the control group were arrested with St.
      Thomas Hospital cardioplegic solution for 3 min then subjected to 30 min of
      global ischaemia in cardioplegic solution, this is followed by reperfusion for 10
      min. In albumin groups, the experimental protocol was the same but 2.25%, 4.5% or
      9% human albumin was added to the cardioplegic solution. All of the hearts were
      compared for their pre-ischaemic and post-ischaemic contractility, heart rate,
      coronary flow, LDH and CK enzyme leakage, and wet/dry weight ratio values. The
      contraction, heart rate (P < 0.01 for both), and coronary flow (only for the 9%
      albumin group, P < 0.05) values in the albumin group were less than the control
      group during the reperfusion period. There was no difference between groups in
      LDH, and CK leakage, and wet/dry weight ratio. The circulation of ischaemic
      hearts in the albumin group were diminished, possibly due to protein
      precipitation. This condition negatively affected the performance of the heart.
      The fact that there is no difference in enzyme leakage and wet/dry weight ratio,
      indicates that this event is not irreversible.

PMID- 9572064
TI  - Cardiac binding of [3H]inositol 1,4,5-trisphosphate following chronic stimulation
      of cyclic AMP signalling in guinea pigs.
AB  - Binding of [3H]inositol 1,4,5-trisphosphate ([3H]IP3) to guinea pig heart has
      been characterised, localised and the effect of the in vivo desensitisation of
      cardiac beta-adrenoceptorcyclic AMP signalling examined. Quantitative
      autoradiography showed highest levels of [3H]IP3 binding associated with coronary
      blood vessels and with the endothelial cells of the aorta and the mitral and
      tricuspid valves. Moderate levels of [3H]IP3 bound to the atrioventricular
      conducting system, cardiac valves and aortic smooth muscle. Lower levels of
      [3H]IP3 binding were detected in atrial and ventricular myocardium. Although the
      phosphoinositide signalling pathway does not contribute greatly to normal cardiac
      function, there is evidence of an increased importance in situations of
      compromised excitation-contraction such as occurs in cardiac failure or with,
      beta-adrenoceptor desensitisation. We examined whether chronic in vivo
      stimulation of beta-adrenoceptor-adenylate cyclase signalling affected cardiac
      binding of [3H]IP3. Infusion of guinea pigs with isoprenaline (400 micrograms kg
      1 h-1, 7 days) tended to reduce [3H]IP3 binding in myocardium although not
      significantly (P > 0.05, n = 4). These data indicate that [3H]IP3 binding has a
      heterogeneous distribution in guinea pig heart with highest levels of binding
      discretely localised to endothelial cells. Desensitisation of beta-adrenoceptor
      cyclic AMP signalling in heart did not lead to upregulation of [3H]IP3 binding.

PMID- 9572065
TI  - Effects of orotic acid on ischaemic/reperfused myocardial function and glycogen
      content in isolated working rat hearts.
AB  - The present study was carried out to investigate the effect of orotic acid on
      ischaemic/reperfused myocardial function and cardiac glycogen content in isolated
      working rat hearts. In a preliminary series of studies, hearts isolated from male
      Wistar rats (300-350 g) were perfused with oxygenated Krebs-Henseleit buffer
      containing cumulative concentrations of orotic acid from 0.01 to 10.00 mg l-1. In
      the concentration range of 0.01-0.10 mg l-1, orotic acid significantly improved
      left ventricular function. Therefore, in the second series of studies, rats were
      treated intravenously with 0.01 mg kg-1 orotic acid for 4 days. Hearts were then
      isolated and subjected to 30 min of global no-flow ischaemia followed by 10 min
      of reperfusion. Orotic acid treatment significantly improved post-ischaemic
      myocardial function and increased pre-ischaemic and post-ischaemic glycogen
      content of the heart. We conclude that orotic acid improves ischaemic/reperfused
      cardiac performance and this effect may be based on the elevation of myocardial
      glycogen content.

PMID- 9572066
TI  - Effect of L-carnitine on myocardial metabolism: results of a balanced, placebo
      controlled, double-blind study in patients undergoing open heart surgery.
AB  - The effects of L-carnitine on cardiac performance after open heart surgery were
      evaluated in a balanced, placebo-controlled, double-blind study in 38 patients.
      Preoperative haemodynamic status was good in all of them. Seventeen subjects
      underwent mitral valve replacement and 19 patients coronary artery bypass
      grafting. Five grams L-carnitine were given intravenously over 2 h, twice daily
      for 5 consecutive days; moreover, 10 g L-carnitine in 1500 ml cardioplegia were
      administered through the aortic root after aortic cross-clamping. Surgery was
      always planned on treatment day 3. The post-ischaemic functional recovery of the
      heart was assessed by clinical parameters, as well as by biochemical and
      ultrastructure evaluations on biopsy specimens. No differences were found between
      the control and the treatment group with respect to all clinical parameters of
      cardiac performance after cardiopulmonary bypass. At anaesthesia induction, serum
      carnitine was significantly increased in treated patients, but carnitine
      concentrations in the right atrial biopsy obtained just before aortic declamping
      were similar in the two groups. In patients with mitral valve replacement, L
      carnitine therapy was associated with significantly higher concentrations of
      pyruvate, ATP and creatine phosphate in papillary muscle. Glycogen levels were
      also higher in the treated group, but the difference was not statistically
      significant. Myocardial ultrastructure on septal biopsies, obtained within 5 min
      from weaning from extracorporeal circulation, showed better preservation scores
      for all considered parameters (nucleus, sarcoplasmic reticulum, mitochondria and
      cellular oedema) in the treated subjects, although the difference reached
      statistical significance only for nuclei. When biochemical and ultrastructural
      data are considered, these findings suggest that L-carnitine improves myocardial
      metabolism. However, it cannot be concluded that L-carnitine provides an
      advantageous support therapy for well-compensated patients requiring cardiac
      surgery. In contrast, the positive effects of L-carnitine on cardiac recovery
      after bypass might become clinically relevant in the surgical setting for
      haemodynamically compromised patients, in which further investigations are
      required.

PMID- 9572067
TI  - Possible functional immunotoxicity of acrylonitrile (VCN).
AB  - Acrylonitrile (vinyl cyanide, VCN), an environmental pollutant, has been shown to
      be an animal and human carcinogen particularly for the GIT. In a previous work
      done in our laboratory, VCN induced immunosuppressive effects as indicated by a
      decrease in plaque forming cell (PFC) response to SRBCs (sheep red blood cell)
      immunization, a marked depletion of spleen lymphocyte subsets by flow cytometric
      analysis as well as bacterial translocation of the normal flora leading to
      brachial lymph node abscess. This work was carried out to evaluate the systemic
      and/or local immunotoxic potential of VCN. Acrylonitrile (2.7 mg kg-1 day-1) was
      given to CD-1 mice once daily for 5, 10 and 15 days. Immunohistochemical
      assessment of the number of cells capable of producing IgA in different
      intestinal compartments (duodenum, jejunum and ileum) revealed a significant
      decrease following VCN treatment. On the contrary, Bromodeoxyuridine (BrdU)
      incorporation in gut epithelial cells (duodenum and ileum) showed a significant
      increase in the same VCN-treated groups of animals. On the other hand,
      [3H]thymidine uptake was significantly decreased in splenocytes stimulated with
      phytohemaglutinin (PHA), Concanavalin-A (Con-A) and Lipopolysaccharide (LPS) and
      derived from animals treated with VCN. The effects of VCN were started after 5
      days and increased up to 15 days of daily treatment in most of the investigated
      parameters. The results suggested that VCN has a profound immunosuppressive
      effect either systemically or locally which could be a contributing factor in its
      GIT carcinogenicity.

PMID- 9572068
TI  - Postnatal development of organic cation transport in the rat liver.
AB  - Previous studies have demonstrated that the small permanently charged organic
      cation 1-methyl-4-phenylpyridinium (MPP+) is avidly taken up by rat hepatocytes.
      The aim of this study was to characterise the postnatal development of hepatic
      uptake of organic cations, using the model compound MPP+. Accumulation of
      [3H]MPP+ by liver slices obtained from rats ranging from 1 day to 7 weeks was
      measured, and the effect of a series of compounds on [3H]MPP+ uptake was
      examined. The accumulation of [3H]MPP+ by liver slices was similar in adult (87.5
      +/- 19.9 pmol g-1; n = 7) and neonatal rats (110.6 +/- 11.5 pmol g-1; n = 15).
      Verapamil, quinidine (100 microM) and progesterone (200 microM) produced very
      marked reductions on [3H]MPP+ uptake at all ages, and the inhibitory effect of
      verapamil and quinidine was maximum in livers from 1-day-old rats. Bilirubin (200
      microM) significantly reduced [3H]MPP+ uptake by liver slices from 1 day, 1 week
      and 7-week-old rats. However, [3H]MPP+ accumulation was reduced by cimetidine,
      vinblastine and daunomycin (100 microM) in 1-day-old rats, but the effect of
      these drugs disappeared as the animals age increased. These findings demonstrate
      that hepatic organic cation uptake capacity is remarkably high shortly after
      birth and suggest that at least two distinct uptake mechanisms are involved in
      this process. These uptake systems are the type I hepatic transporter of organic
      cations, active from birth to adulthood, and P-glycoprotein, active only in very
      young rats.

PMID- 9572069
TI  - The effects of moclobemide on the yohimbine-induced anxiogenic action in the
      elevated plus-maze.
AB  - Moclobemide (MOC), a selective and reversible MAO-A inhibitor, was claimed to
      have both anxiolytic and anxiogenic properties. Therefore, we assessed whether:
      (1) acute and subchronic (10 days) MOC treatments, in doses which display
      antidepressant activity, affect the performance of rats in the elevated plus-maze
      that provides detection of both anxiolytic and anxiogenic properties in the same
      experimental conditions; (2) the alpha 2 antagonist yohimbine (YOH), which
      increases noradrenaline (NA) release, is able to modify the effects of MOC
      treatments in the elevated plus-maze. The results showed that MOC, at doses of 10
      and 20 mg kg-1 i.p. either acutely or subchronically administered, significantly
      reduced the immobility time in the forced swimming test in rats. In other words,
      it displayed antidepressant activity. In the elevated plus-maze, acutely
      administered MOC (20 mg kg-1 i.p.) significantly increased both the percentage of
      open arm entries and the time spent in open arms, while only the former parameter
      was increased in response to 10 mg kg-1 i.p. MOC treatment. Thus, the anxiolytic
      action of MOC at a dose of 20 mg kg-1 i.p. was more prominent. Subchronically
      administered MOC at both doses significantly increased the two parameters. Hence,
      it can be stated that anxiolytic action of subchronically administered MOC
      appears to be more pronounced. Acutely administered YOH (0.5 mg kg-1 i.p.) showed
      anxiogenic effect in the elevated plus-maze. However, in both acutely and
      subchronically MOC-treated animals, YOH failed to exert its anxiogenic effect.
      This implies the importance of NA-gic activity in the MOC-induced anxiolytic
      action.

PMID- 9572070
TI  - 6-OHDA bilateral lesions to the nucleus septi lateralis attenuate vasopressin
      improvement of recall in rats.
AB  - The investigation was aimed at investigating whether the dopaminergic projection
      arriving at the nucleus septi lateralis (NSL) is involved in the facilitatory
      effect of vasopressin (AVP) on memory retrieval. The bilateral 6-OHDA lesions to
      the NSL were made in 20 male Wistar rats before testing the
      intracerebroventricular (i.c.v.) AVP injection on recall in a passive avoidance
      situation. Eighteen additional rats served as sham-operated controls. Thirty
      minutes before surgery rats were pre-treated with an intraperitoneal injection of
      25 mg kg-1 of desmethylimipramine, an inhibitor of norepinephrine uptake. Sixteen
      lesioned and 16 sham-operated rats were included in the study. AVP (1 microgram,
      i.c.v.) given 15 min before the retention testing significantly improved
      latencies both in lesioned and in sham-operated rats in comparison with the
      respective i.c.v. saline-injected animals. However, bilateral lesions to the NSL
      significantly diminished the facilitatory effect of AVP on recall. The
      insignificant decrease of spontaneous psychomotor activity in rats lesioned to
      the NSL was unlikely to interfere with the cognitive effect of AVP. These results
      suggest that dopaminergic projection to the NSL is involved in the facilitatory
      effect of AVP on the retrieval process in a passive avoidance situation.

PMID- 9572071
TI  - The responsiveness of the endogenous inhibitor of cAMP-dependent protein kinase
      to isoproterenol after prolonged treatment with nifedipine.
AB  - In the present study the response of the type I inhibitor activity to
      isoproterenol was used as an indirect index both of cAMP generation and beta
      adrenergic receptor reactivity. Our results suggest that nifedipine, after
      prolonged treatment, produces subsensitivity in beta-adrenergic transmission
      without changes in the basal level of cAMP. Administration of isoproterenol
      produced a dose-dependent decrease of the type I inhibitor activity (an
      endogenous inhibitor of cAMP-dependent protein kinase, Walsh inhibitor) in the
      frontal cortex and hippocampus of rats. Prolonged treatment with nifedipine (5 mg
      kg-1 i.p., twice daily, 21 days) did not change the basal activity of the type I
      inhibitor, but markedly reduced the response of the type I inhibitor activity to
      isoproterenol. In the treated animals a significant decrease of the type I
      inhibitor was seen when isoproterenol was used in much higher doses than in
      control rats.

PMID- 9572072
TI  - Estimation of drug excretion rate from blood into the gut using a three
      compartment closed model.
AB  - After administration and absorption, some drugs can be excreted via various
      mechanisms from blood into the gut; the determination of this drug excretion rate
      may have important clinical and pharmaceutical implications. A three-compartment
      closed model with first-order absorption was designed using absorption, blood and
      eliminated compartments to estimate the drug transfer rate from blood into the
      gut. Theoretically, the excretion rates of drugs whose blood concentrations can
      be described by the one-compartment open model with first-order absorption can be
      estimated using the developed model. This theoretical deduction was supported by
      100 Monte Carlo simulations performed in the present study. A sensitivity
      analysis suggests that the estimated drug transfer rate from blood into gut is
      very sensitive to blood drug concentrations. Meanwhile, an example also shows the
      limitation of the developed model.

PMID- 9572073
TI  - [Nobel prize for prions].

PMID- 9572074
TI  - [Function of type Rab/Ypt GTPases and their escort proteins in the regulation of
      membrane transport].

PMID- 9572075
TI  - [DNA oxidative damages--free radical modification of bases and sugar moieties].

PMID- 9572076
TI  - [Quantitative PCR and its application in hematologic molecular diagnostics].

PMID- 9572077
TI  - [Genetic recombination (+) RNA viruses].

PMID- 9572079
TI  - [Non-genomic action of steroids in the nervous system].

PMID- 9572078
TI  - [RNA tectonics].

PMID- 9572080
TI  - [Disturbances in copper homeostasis are the main cause of serious human
      diseases].

PMID- 9572081
TI  - [Photosynthetic isoform of phosphoenolpyruvate carboxylase--transcriptional and
      post-translational regulation].

PMID- 9572082
TI  - Back to the future: the neurobiology of major depression.

PMID- 9572083
TI  - Effects of tryptophan depletion in fully remitted patients with seasonal
      affective disorder during summer.
AB  - BACKGROUND: Deficiencies in brain serotonin function are believed to play an
      important role in the pathophysiology of seasonal affective disorder/winter type
      (SAD). However, no direct evidence has been reported so far that lowered brain
      serotonin activity causes the symptoms of SAD. METHODS: We studied 11 SAD
      patients who had suffered recurrent winter depressive episodes of SAD and were
      fully recovered and off treatment during the summer. In a randomized, balanced,
      double-blind crossover design patients received two amino acid beverages, one
      containing tryptophan and the other containing no tryptophan but otherwise
      identical. Behavioural ratings and plasma total and free tryptophan
      concentrations were assessed at baseline before administration of the amino acid
      beverages and at several time points afterwards. RESULTS: The tryptophan-free
      amino acid beverage induced significant decreases of plasma total and free
      tryptophan levels and both levels increased during sham depletion (condition x
      time interaction: P < 0.001). Tryptophan depletion, but not sham depletion caused
      a transient return of depressive symptoms (condition x time interaction: P <
      0.001). CONCLUSIONS: The present study demonstrates that SAD patients in
      remission during the summer are vulnerable to a return of depression when
      depleted of tryptophan. This finding supports the importance of serotonergic
      mechanisms in the pathophysiology of SAD.

PMID- 9572084
TI  - Adrenal steroid secretion and major depression in 8- to 16-year-olds, III.
      Influence of cortisol/DHEA ratio at presentation on subsequent rates of
      disappointing life events and persistent major depression.
AB  - BACKGROUND: An investigation of the association between diurnal changes in
      cortisol and DHEA levels, or in the cortisol/DHEA ratio at five different time
      points at presentation, and the occurrence of undesirable life events (losses,
      dangers to self and others, disappointments) during follow-up, and the outcome of
      major depression at 36 weeks were investigated. METHODS: Psychosocial and
      endocrine assessment of a consecutive cohort (N = 68) of 8- to 16-year-old
      subjects with first episode major depression reassessed 12 months after
      presentation using a repeat measures design. RESULTS: Higher cortisol/DHEA ratios
      at 20.00 or 24.00 h predicted persistent major depression. Basal levels of either
      hormone alone or cortisol/DHEA ratios at the other three time points (08.00,
      12.00 or 16.00 h) did not. High cortisol/DHEA ratios (i.e. values greater than
      the 60th percentile) at both evening points (20.00 and 24.00 h) also predicted
      the occurrence of subsequent disappointing life events but no other category of
      undesirable event. Both high evening cortisol/DHEA ratio at 20.00 h and one or
      more severely disappointing life events between presentation and follow-up
      predicted persistent major depression: 86% of subjects with both of these factors
      were still depressed at 36 weeks whereas 81% with neither factor were not.
      CONCLUSIONS: The finding that it is depressed subjects with high cortisol/DHEA
      ratios at presentation who are specifically at risk for subsequent disappointing
      life events suggests a putative role for these adrenal steroids in abnormal
      cognitive or emotional processes associated with disturbed interpersonal
      behaviour.

PMID- 9572085
TI  - Neuropsychological performance and plasma cortisol, arginine vasopressin and
      oxytocin in patients with major depression.
AB  - BACKGROUND: The aim of the study was to search for the existence of, and define,
      a possible relationship between performance in neuropsychological tests and
      baseline concentrations of plasma cortisol, vasopressin and oxytocin in
      medication-free patients with a major depressive episode. METHODS: Measures of
      depression and anxiety were obtained and a neuropsychological battery was
      presented. Blood for neuropeptide analysis was drawn by venepuncture at 8.00,
      16.00 and 23.00 h. RESULTS: The melancholic patients performed less well on the
      neuropsychological battery than did the non-melancholic patients, but these
      differences could be accounted for by the severity of the illness. Global
      intellectual functioning was negatively correlated with mean baseline plasma
      concentrations of cortisol. Patients with high mean plasma vasopressin
      concentrations remembered more auditory presented words in the delayed recall
      test and produced more intrusions in the visual word learning list than did
      patients with low or normal mean plasma vasopressin concentrations. No
      association was found between neuropsychological performance and plasma
      concentrations of oxytocin. CONCLUSIONS: Our findings support the hypothesis that
      elevated baseline plasma cortisol concentrations are related to cognitive
      impairment in depressed patients and the hypothesis that the neuropeptide
      vasopressin independently enhances memory, directly or indirectly through
      increasing arousal and attention.

PMID- 9572086
TI  - Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in
      chronic fatigue syndrome.
AB  - BACKGROUND: Opioidergic pathways have an inhibitory regulatory influence on the
      hypothalamic-pituitary-adrenal axis (HPA) in man. Previous studies have suggested
      impairment of pituitary-adrenal activation in chronic fatigue syndrome (CFS). We,
      therefore, decided to investigate the extent of opioid inhibition of HPA activity
      in CFS as a possible explanation for the reputed HPA hypofunctioning in patients
      with CFS. METHOD: Thirteen patients with CFS, diagnosed according to CDC
      criteria, were compared with thirteen healthy subjects. Adrenocorticotropin
      (ACTH) and cortisol (CORT) responses were measured following the administration
      of the opiate antagonist naloxone. RESULTS: Baseline ACTH and cortisol levels did
      not differ between the two groups. The release of ACTH (but not cortisol) was
      significantly blunted in the CFS subjects compared with controls. CONCLUSIONS:
      Naloxone mediated activation of the HPA is attenuated in CFS. Excessive opioid
      inhibition of the HPA is thus an unlikely explanation for the HPA dysregulation
      in this disorder.

PMID- 9572087
TI  - Abnormal 5-HT1D receptor function in major depression: a neuropharmacological
      challenge study using sumatriptan.
AB  - BACKGROUND: Sumatriptan, a specific agonist at 5-HT1D receptors, stimulates
      release of growth hormone (GH) and inhibits release of prolactin (PRL). METHODS:
      We gave sumatriptan (6 mg subcutaneously) to 11 patients with unipolar major
      depression and 11 control subjects matched for age, sex, weight and menstrual
      cycle phase. Serum GH and PRL were measured at 0, 15, 30, 45, 60 and 90 min after
      injection. RESULTS: The maximal rise in GH was significantly reduced in the
      depressed patients, with 60% showing no increase over baseline compared with 18%
      of controls. There were no significant differences in PRL responses. CONCLUSIONS:
      These results suggest reduced sensitivity of 5-HT1D receptors in major
      depression. Our results and those of studies investigating 5-HT1A receptors imply
      that both 5-HT1A and 5-HT1D autoreceptors may show reduced function in major
      depression.

PMID- 9572088
TI  - The influence of psychological stress on total serum protein and patterns
      obtained in serum protein electrophoresis.
AB  - BACKGROUND: Significant alterations in total serum protein (TSP) patterns
      obtained in serum protein electrophoresis and serum proteins have been reported
      in patients with major depression and in subjects submitted to a combination of
      psychological and physical stress. The aim of the present study was to examine
      the effects of academic examination stress, on TSP and patterns obtained in serum
      protein electrophoresis. METHODS: TSP and the concentrations and percentages of
      the major electrophoretically separated serum proteins were measured in 41
      healthy biomedical students the day before a difficult academic examination (i.e.
      the stressful condition), as well as a few weeks before and after the stressful
      condition (i.e. two baseline conditions). RESULTS: Academic examination stress
      increased TSP and the alpha 1, alpha 2, beta and gamma concentrations in stress
      reactors, but not in stress non-reactors (as defined by changes in the Perceived
      Stress Scale). Academic examination stress reduced the percentage of albumin in
      the stress-reactors, but not in stress non-reactors. There were significant
      positive relationships between the stress-induced changes in TSP and serum alpha
      2, beta and gamma concentrations and the stress-induced changes in the Perceived
      Stress Scale. CONCLUSIONS: The results show that even mild psychological stress
      of short duration can lead to measurable changes in TSP and in patterns obtained
      in serum protein electrophoresis.

PMID- 9572089
TI  - The dexamethasone suppression test in schizophrenia.
AB  - BACKGROUND: Cortisol non-suppression following the dexamethasone suppression test
      (DST) has been found to a variable extent in schizophrenia. The aetiology is
      unclear but may be related to depression or negative symptoms. METHODS: The DST
      was administered to 64 patients with DSM-IV schizophrenia. All patients were
      screened for DSM-IV major depression and rated on the Hamilton Rating Scale for
      Depression (HRSD), Scale for Assessment of Negative Symptoms (SANS) and the Brief
      Psychiatric Rating Scale (BPRS). RESULTS: DSM-IV criteria for major depression
      was fulfilled by 36% of the patients and 42% of patients had a history of
      parasuicide. Four patients had undetectable levels of dexamethasone and were
      excluded from the endocrine analyses. Only one remaining patient had a cortisol
      level above the cut-off point (> 138 nmol/l), indicating escape from
      dexamethasone suppression. The post-dexamethasone cortisol level correlated
      significantly with HRSD and BPRS scores but not with the SANS. The SANS and HRSD
      scores were not correlated, but they were independently correlated with the BPRS
      score. CONCLUSIONS: In contrast to some other work, rates of dexamethasone non
      suppression were very low; together with the high rates of depression, this
      suggests that depression in schizophrenia may have a different neuroendocrine
      profile from major depressive disorders. Failure to measure dexamethasone levels
      can be misleading.

PMID- 9572090
TI  - Cognitive function and dementia in six areas of England and Wales: the
      distribution of MMSE and prevalence of GMS organicity level in the MRC CFA Study.
      The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).
AB  - BACKGROUND: This two-stage prevalence survey involved geographically delimited
      areas, four urban (Liverpool, Newcastle, Nottingham and Oxford) and two rural
      (Cambridgeshire and Gwynedd), including institutions. METHODS: Stratified random
      population samples of people in their 65th year and above, from Family Health
      Service Authorities were studied. The sample was stratified (65-74 years and > or
      = 75) to provide equal numbers. In Liverpool equal numbers in 5 year age groups
      were taken. After an initial screening interview, approximately 20% were selected
      on the basis of age, AGECAT organicity confidence level and MMSE score to proceed
      to a detailed assessment interview from which the full AGECAT organicity
      confidence level could be derived. RESULTS: Major influences on MMSE were
      confirmed as age, sex, social class and educational level. Estimates of
      prevalence of AGECAT O3 and above for each centre and the entire sample according
      to age are given, based on 1991 Census population structure, and suggest that
      around half a million (543,400) people in England and Wales would be defined as
      case level by this method. The five centres employing the same methodology showed
      no heterogeneity in prevalence. CONCLUSIONS: Prevalence of cognitive impairment
      and dementia appear not to vary widely across the centres examined in this study,
      which provides stable estimates by age and sex for AGECAT O3 and above, and norms
      for MMSE. Using these estimates as an indication of the size of the population
      affected, around 550,000 individuals in England and Wales would be expected to be
      suffering from dementia of mild or greater severity.

PMID- 9572091
TI  - A prospective population-based cohort study of the effects of disablement and
      social milieu on the onset and maintenance of late-life depression. The Gospel
      Oak Project VII.
AB  - BACKGROUND: Population-based studies suggest substantial co-morbidity between
      physical illness and depression in late-life. However, a causal relationship has
      not been established. If a relationship exists, it is important to establish
      which aspects of poor health determine risk for depression, and which factors
      confer vulnerability or resilience in the face of poor health. We investigate the
      role of disablement, measured as impairment, disability and handicap. METHODS: A
      prospective population-based cohort study, comprising an index assessment and 1
      year follow-up, of all residents aged 65 years or over, of an electoral ward in
      London, UK (N = 889). RESULTS: The prevalence of SHORT-CARE pervasive depression
      was 17.7% at index assessment. The 1 year onset rate for pervasive depression was
      12.0%, and the 1 year maintenance rate 63.2%. There was a high mortality rate
      among the depressed. Disablement, particularly handicap was the most important
      predictor of the onset of depression (population attributable fraction, 0.69).
      Lack of contact with friends was a direct risk factor but also modified the
      association between handicap and depression. Marriage was protective for men, but
      a risk factor for women. Maintenance of depression was predicted by low levels of
      social support and social participation, rather than by disablement. CONCLUSIONS:
      It seems likely that disablement, specifically handicap, is the chief cause of
      onsets of depression in late-life. Genetic predisposition, early adversity and
      serious life events may play a less prominent role than in earlier life.
      Effective prevention of late-life depression requires attention at the structural
      level to the sources of handicap within communities.

PMID- 9572092
TI  - Is schizophrenia a disorder of all ages? A comparison of first episodes and early
      course across the life-cycle.
AB  - BACKGROUND: The heterogeneity of schizophrenic and delusional syndromes by age of
      onset has frequently been discussed. METHODS: The age distribution of symptoms
      and 5 year course was studied in a population-based first-episode sample admitted
      to 10 psychiatric hospitals before the age of 60 (N = 232) and in a clinical
      sample without age limit of consecutive first admissions to a single hospital (N
      = 1109), both samples with broadly diagnosed schizophrenia. RESULTS: Early-onset
      patients, particularly men, presented more non-specific symptoms and higher PSE
      CATEGO total scores than late-onset patients. In men, symptom severity decreased
      with increasing age of onset. In women, it remained stable except for an increase
      of negative symptoms with late-onset. Only a few symptoms changed markedly with
      age: disorganization decreased, while paranoid and systematic delusions increased
      steeply across the whole age of onset range. Pronounced age- and sex-differences
      emerged in illness behaviour, socially negative behaviour and substance abuse.
      Within the group of late-onset psychoses there were continuous transitions in
      symptom profiles and no discrimination between schizophrenia and paranoid
      psychosis or late paraphrenia. The main determinant of social course was onset
      level of social development. Early-onset patients did not improve in social
      status, while late-onset patients, prior to retirement, suffered considerable
      decline in social status. CONCLUSIONS: Gender differences in age at onset and in
      age trends in symptom severity support the hypothesis of a mild protective effect
      of oestrogen. Social course results from an interplay between biological factors
      (age at onset and functional impairment) and development factors (level of social
      development at onset and illness behaviour).

PMID- 9572093
TI  - Is the decline in diagnoses of schizophrenia caused by the disappearance of a
      seasonal aetiological agent? An epidemiological study in England and Wales.
AB  - BACKGROUND: Studies from several countries have shown a decline, in the last few
      decades, of the number of admissions with a diagnosis of schizophrenia. This
      could be due to a fall in the incidence of schizophrenia, but it also could be
      due to confounding factors. The hypothesis tested in the study is that the
      incidence of schizophrenia is actually falling because of a decrease in the
      presence of a seasonal aetiological agent. METHODS: The hypothesis was tested by
      analysing the dates of birth of the patients discharged with a diagnosis of
      schizophrenia from NHS hospitals in England and Wales and would be confirmed by
      an appropriate change in the seasonality of the births over time. RESULTS:
      Evidence of seasonality has been observed in the schizophrenic births, but with
      no significant change over time. CONCLUSIONS: The fall in first admissions with a
      diagnosis of schizophrenia does not seem to be due to a change in the prevalence
      of a seasonal aetiological factor. Therefore, either there has been a reduction
      in incidence due to a change in a non-seasonal agent, or the incidence of
      schizophrenia is not changing and the fall in first admissions is due to
      confounding factors.

PMID- 9572094
TI  - The Zurich long-term outcome study of child and adolescent psychiatric disorders
      in males.
AB  - BACKGROUND: Within the framework of developmental psychopathology the outcome of
      male former child and adolescent psychiatric patients at age 36 or 38 was studied
      in order to add to the limited knowledge in this field. METHODS: A total of 269
      former child psychiatric patients of male sex and a control group of more than
      2700 men, who were all born in 1952, were compared with regard to mortality,
      delinquency and adult psychiatric disorders. The study was based on case-file
      data from assessments conducted with the child and adolescent psychiatric
      patients and on adults, derived from either federal registers (mortality,
      delinquency) or army health records and records of the psychiatric facilities of
      the canton. The study is based on lifetime prevalence rates. RESULTS: The two
      samples did not differ with regard to mortality rates. Delinquency tended to be
      more prevalent and psychiatric disorders were significantly more prevalent among
      the former child psychiatric patients. Close to 10% of the latter group showed
      major delinquency, one-quarter was psychiatrically disturbed and 30% displayed
      one of these two indicators or maladjustment at least once during the follow-up
      period. A correspondence in pattern of varying between child and adult
      psychiatric spectrum disorders was observed. Whereas the type of child and
      adolescent psychiatric disorders did not predict adult maladjustment, there was
      some indication that deprived environments, broken homes and parental psychiatric
      disorders during childhood increased the likelihood of poor adult outcome.
      CONCLUSIONS: This study clearly underlines the long-term negative effects of
      child and adolescent mental abnormalities in males.

PMID- 9572095
TI  - Autism, affective and other psychiatric disorders: patterns of familial
      aggregation.
AB  - BACKGROUND: The liability to autism confers a risk for a range of more subtle
      autistic-like impairments, but it remains unclear whether it also confers a risk
      for other psychiatric disturbances. METHODS: To investigate this, we studied the
      pattern of familial aggregation of psychiatric disorders in relatives of 99
      autistic and 36 Down's probands, using family history and direct interview
      measures. RESULTS: Family history data showed that motor tics, obsessive
      compulsive (OCD) and affective disorders were significantly more common in
      relatives of autistic probands and that individuals with OCD were more likely to
      exhibit autistic-like social and communication impairments. Direct interview data
      confirmed the increased rate of affective disorders (especially major depressive
      disorder) in the first-degree relatives. There was no evidence to indicate
      significant co-morbidity between affective disorders and the broadly defined
      phenotype of autism. Moreover, the characteristics of the probands' and the
      relatives' that were associated with the liability to familiarity of the broader
      phenotype of autism differed from those that predicted the liability to the
      familiarity of affective disorders. Examination of the onset of affective
      disorders suggested that the increased risk was not confined to the period
      following the birth of the child with autism. CONCLUSIONS: Overall, the results
      indicated that OCD, but not affective disorders, may index an underlying
      liability to autism. They also indicated that the increased risk of affective
      disorders was not solely the consequence of the stress of raising a child with
      autism and that further research will be required to clarify the mechanisms
      involved.

PMID- 9572096
TI  - Theory of mind and psychoses.
AB  - BACKGROUND: A cardinal feature of schizophrenia is the sufferer's difficulty in
      interacting appropriately within the social milieu. This deficit has recently
      been associated with the concept of theory of mind, more commonly constructed as
      a working model to understand behavioural patterns in autistic children. In this
      paper the complex relationships between theory of mind, IQ and psychoses are
      addressed. METHODS: Five experimental groups were used; non-psychiatric controls,
      affective disorder, schizophrenia with normal pre-morbid IQ, schizophrenia with
      pre-morbid IQ in the mildly learning disabled range, and mild learning disability
      with no history of psychiatric illness. All subjects were given a first order
      Theory of Mind Task and if successful, a second order Theory of Mind Task was
      then administered. All subjects were rated using the Positive and Negative
      Symptom Scale (PANSS). RESULTS: Subjects with schizophrenia and subjects with
      mild learning disability show impaired ability on a second order theory of mind
      task. However, when patients who are unable to answer reality questions are
      removed from the analysis specific impairment of theory of mind is only seen in
      subjects with schizophrenia. Furthermore, this impairment is relatively specific
      to particular psychopathological clusters in subjects with schizophrenia. Even
      though the same clusters of psychopathology are also seen in patients with
      affective disorder, their presence is not associated with poor second order
      theory of mind performance. CONCLUSIONS: Impaired theory of mind on second order
      tests is specific to schizophrenia when compared to mild learning disability and
      affective disorder control groups. Subjects with schizophrenia and pre-morbid
      mild learning disability show greater impairment than subjects with schizophrenia
      and a pre-morbid IQ within the normal range.

PMID- 9572097
TI  - The relationship between negative emotions and acute subjective and objective
      symptoms of childhood asthma.
AB  - BACKGROUND: Children with asthma are vulnerable to negative emotions, but
      clinical observations and research suggest that negative emotions can also be
      precipitants of asthma attacks. Empirical data provided mixed results. The
      hypothesis was tested that negative emotions influence subjective rather than
      objective symptoms of asthma, breathlessness and airways obstruction,
      respectively. METHODS: Forty asthmatic children (aged 7 to 18 years) were
      randomly assigned to one of four experimental conditions: 1, viewing an emotional
      film of 10 min; 2, performing standardized physical exercise of modest intensity
      up to a heartbeat of 170 b/min; 3, combination of conditions, order conditions, 1
      + 2; and 4, combination of conditions, order conditions 2 + 1. Lung function,
      breathlessness and state anxiety were measured pre-test and post-test.
      Respiration sounds were recorded continuously for assessment of emotional
      breathing patterns. RESULTS: The data and responses to exit questions, confirmed
      a successful induction of anxiety via increased state anxiety and respiratory
      rate. Viewing the emotional film did not by itself enhance airways obstruction or
      breathlessness. Airways obstruction and breathlessness increased significantly
      after exercise only. Significantly more breathlessness was reported when negative
      emotions preceded exercise. Breathlessness was statistically independent of lung
      function, severity of asthma, symptoms in the past 4 weeks, anxiety or age.
      CONCLUSION: Negative emotions affect subjective, rather than objective symptoms
      of childhood asthma. It was suggested that children in a negative emotional
      state, uncertain about the condition of their airways, are inclined to interpret
      exercise-related general sensations (fatigue, heart pounding, sighing) in line
      with expectations as symptoms of airways obstruction. Consequently, they may
      report relatively high breathlessness, irrespective of actual objective symptoms
      of asthma.

PMID- 9572098
TI  - Selected symptoms associated with sexual and physical abuse history among female
      patients with gastrointestinal disorders: the impact on subsequent health care
      visits.
AB  - BACKGROUND: Despite a growing literature pointing to the deleterious health
      effects of sexual and physical abuse history, few studies provide evidence about
      which medical symptoms are most affected. The aim of this paper is to determine
      the impact of sexual and physical abuse history on a selected set of medical
      symptoms, and to test how such abuse, medical symptoms and functional disability
      may affect subsequent health care visits. METHODS: We studied 239 women from a
      referral-based gastroenterology clinic; follow-up data were available on 196 of
      these women. All women were interviewed about sexual and physical abuse history.
      RESULTS: Women with abuse history, particularly those with severe abuse, were
      much more likely to report somatic symptoms related to panic (e.g. palpitations,
      numbness, shortness of breath), depression (e.g. difficulty sleeping, loss of
      appetite), musculoskeletal disorders (e.g. headaches, muscle aches), genito
      urinary disorders (e.g. vaginal discharge, pelvic pain, painful intercourse),
      skin disturbance (e.g. rash) and respiratory illness (e.g. stuffy nose).
      Furthermore, we found that the severity of abuse history, somatic symptoms and
      functional disability predicted 30% of the variance in health care visits during
      the subsequent year, and that the effect of abuse severity on visits was
      explained by abused women having more somatic symptoms and functional disability.
      CONCLUSIONS: Patients' reports of abuse history, somatic symptoms and functional
      disability appear to be important factors in explaining the number of health care
      visits among a clinic sample of women with gastrointestinal disorders.

PMID- 9572100
TI  - A comparative study of insight scales and their relationship to
      psychopathological and clinical variables.
AB  - BACKGROUND: Research on the subject of insight has been hampered by difficulties
      in definition and reliable measurement. METHODS: We compared several rating
      scales to measure insight on a group of 33 psychotic patients as well as
      assessing patients' psychopathology, clinical characteristics and cognitive
      functioning. RESULTS: Most currently used scales showed a high degree of inter
      correlation. Measures of insight related strongly to the presence of delusions;
      grandiosity (inversely), and depression (positively). Higher insight scores
      correlated with indices of treatment compliance and inversely with substance
      abuse. Measures of pre-morbid IQ and impaired executive functioning, including
      the Wisconsin Card Sorting Test were not associated with poor insight.
      CONCLUSIONS: The study highlights aspects of psychopathology and clinical
      variables particularly related to insight and supports the continued use of
      standardized scales in further research in this area.

PMID- 9572099
TI  - Factors associated with referral to psychiatric care by general practitioners
      compared with self-referrals.
AB  - BACKGROUND: The gatekeeper function of the general practitioner (GP) in the
      pathway to specialized psychiatric services was investigated in this study, which
      is part of the Nordic Comparative Study on Sectorized Psychiatry. The question
      addressed in this paper is whether different sociodemographic and clinical
      factors as well as factors related to service utilization are associated with
      referral from the GP compared with self-referrals (including referrals from
      relatives). METHODS: The study comprised a total of 1413 consecutive patients,
      admitted during 1 year to five psychiatric centres in four Nordic countries. The
      centres included in this study were those that accepted non-medical referrals.
      Only new patients (not in contact with the service for at least 18 months) were
      included. RESULTS: Increasing age was the only sociodemographic factor
      significantly associated with referral by the GP. The clinical factors
      (psychosis, being totally new to psychiatry and being in need of in-patient
      treatment) and some treatment characteristics (planned out-patient treatment and
      involuntary in-patient treatment), were all significantly associated with
      referral by the GP. Some indication was found that self-referred patients have
      shorter episodes of care. CONCLUSIONS: The findings were remarkably stable across
      the different centres indicating a general pattern. This study extends previous
      work on the role of GPs in the pathway to specialized psychiatric services and
      indicates that the GP has an important gatekeeper function for the most disabled
      patients.

PMID- 9572101
TI  - Self-reported mental distress under the shifting daylight in the high north.
AB  - BACKGROUND: The validity of the concept of seasonal affective disorder and the
      causal link to lack of daylight in winter is controversial. There is a need for
      investigations in large samples of the general population at different latitudes
      and within general research contexts to avoid selective response bias and
      sensitization of the population. METHODS: During a study of health effects of the
      air pollution from Russia in a small community at 70 degrees north, a self
      administered questionnaire was filled in by 3736 inhabitants, 60.8% of the total
      population between 18 and 69 years. Three questions concerned depression,
      sleeping problems and other problems related to the two contrasting seasons with
      regard to daylight. RESULTS: Twenty-seven per cent reported to have some kind of
      problem in the dark period. Most frequently reported were sleeping problems
      during winter, in 19.9% of women and 11.2% of men. Self-reported depression in
      winter was found in 11.1% of women and 4.8%% of men. Sleeping problems increased
      with age, while depression was most often reported by middle-aged people. The
      only other reported problem in winter was fatigue. The adjusted relative risk
      (RR) for winter depression in women compared to men was 2.5 (95% confidence
      interval: 1.9-3.2). Very few had problems in summer. CONCLUSIONS: In the high
      north, one-third of the women and one-fifth of the men experience problems with
      sleep, mood or energy related to season. The prevalence of self-reported
      depression was surprisingly low in winter considering the lack of daylight.

PMID- 9572102
TI  - Stability of expressed emotion in relatives of those with schizophrenia and its
      relationship with burden of care and perception of patients' social functioning.
AB  - BACKGROUND: There is evidence that high expressed emotion (EE) in relatives of
      patients with schizophrenia is associated with higher levels of burden of care,
      and with worse perception of patient's social functioning. However, it is not
      clear whether changes in EE levels over time are associated with changes in
      relatives' burden of care and their perception of patients' social functioning.
      METHODS: Fifty patients with a diagnosis of schizophrenia and 50 relatives were
      included in the study soon after patients' admission to hospital. Thirty-six
      relatives and 31 patients were re-assessed 9 months after patients' discharge.
      Both assessments included patients' symptomatology and relatives' EE levels,
      burden of care, and perception of patients' social functioning. RESULTS: Twenty
      three relatives (64%) had the same EE level in both assessments, nine (25%) had
      changed from high to low EE, and four (11%) from low to high EE. Improvement in
      burden and perception of patients' social role performance were significantly
      more accentuated among relatives who changed from high to low EE than among
      relatives who had a stable EE level. Variables that best predicted changes in EE
      levels were changes in burden scores and number of hours of contact between
      patients and relatives at follow-up. CONCLUSIONS: Change in EE is associated with
      change in circumstances and burden. Findings support the idea that EE is better
      understood in an integrative model.

PMID- 9572103
TI  - Executive function in first-episode schizophrenia.
AB  - BACKGROUND: We tested the hypothesis that schizophrenia is primarily a
      frontostriatal disorder by examining executive function in first-episode
      patients. Previous studies have shown either equal decrements in many cognitive
      domains or specific deficits in memory. Such studies have grouped test results or
      have used few executive measures, thus, possibly losing information. We,
      therefore, measured a range of executive ability with tests known to be sensitive
      to frontal lobe function. METHODS: Thirty first-episode schizophrenic patients
      and 30 normal volunteers, matched for age and NART IQ, were tested on
      computerized test of planning, spatial working memory and attentional set
      shifting from the Cambridge Automated Neuropsychological Test Battery.
      Computerized and traditional tests of memory were also administered for
      comparison. RESULTS: Patients were worse on all tests but the profile was non
      uniform. A componential analysis indicated that the patients were characterized
      by a poor ability to think ahead and organize responses but an intact ability to
      switch attention and inhibit prepotent responses. Patients also demonstrated poor
      memory, especially for free recall of a story and associate learning of unrelated
      word pairs. CONCLUSIONS: In contradistinction to previous studies, schizophrenic
      patients do have profound executive impairments at the beginning of the illness.
      However, these concern planning and strategy use rather than attentional set
      shifting, which is generally unimpaired. Previous findings in more chronic
      patients, of severe attentional set shifting impairment, suggest that executive
      cognitive deficits are progressive during the course of schizophrenia. The
      finding of severe mnemonic impairment at first episode suggests that cognitive
      deficits are not restricted to one cognitive domain.

PMID- 9572104
TI  - Well-being therapy. A novel psychotherapeutic approach for residual symptoms of
      affective disorders.
AB  - BACKGROUND: There is increasing awareness of the prognostic value of residual
      symptomatology in affective disorders and of the need for specific therapeutic
      strategies in this phase of illness. The aims of the study were to apply a novel,
      short-term psychotherapeutic approach for increasing well-being, based on Ryff's
      conceptual model, to remitted patients with affective disorders and to compare
      the results with those obtained with symptom-oriented cognitive behavioural
      strategies. METHODS: Twenty patients with affective disorders (major depression,
      panic disorder with agoraphobia, social phobia, generalized anxiety disorder,
      obsessive-compulsive disorder) who had been successfully treated by behavioural
      or pharmacological methods were randomly assigned to a well-being enhancing
      therapeutic strategy (well-being therapy) or cognitive-behavioural treatment of
      residual symptoms. RESULTS: Both well-being and cognitive-behavioural therapies
      were associated with a significant reduction of residual symptoms. However, a
      significant advantage of well-being therapy over cognitive-behavioural strategies
      was observed with observer-rated methods. DISCUSSION: These preliminary results
      suggest the feasibility of well-being therapy in the residual stage of affective
      disorders. Further research should determine its value as a relapse-preventive
      strategy in specific mood and anxiety disorders.

PMID- 9572105
TI  - Aberrant interleukin-2 receptor-mediated blastoformation of peripheral blood
      lymphocytes in a severe major depressive episode.
AB  - BACKGROUND: We examined interleukin-2 (IL-2) related immune pathways in
      depression to elucidate mechanisms underlying various immunological disturbances
      associated with depression. METHODS: Subjects comprised 35 unmedicated patients
      with a major depressive episode without psychotic features and 36 age- and sex
      matched healthy volunteers. The immune parameters examined included the numbers
      of B and T cells, IL-2 receptor-mediated blastoformation (IL-2R-mediated
      blastoformation), IL-2 production and expression of the IL-2 receptor alpha
      subunit. RESULTS: The patients with a severe episode showed significantly lower
      IL-2R-mediated blastoformation than the controls. There was a statistically
      significant negative correlation between IL-2R-mediated blastoformation and the
      severity of depression at the time of entry. CONCLUSION: The reduced IL-2R
      mediated blastoformation may partly explain several previously reported abnormal
      immune functions associated with depression.

PMID- 9572106
TI  - Performance on the delayed word recall (DWR) fails to differentiate clearly
      between depression and Alzheimer's disease.

PMID- 9572107
TI  - Studies into issues of 'race' and culture in psychiatry.

PMID- 9572108
TI  - Molecular and cellular regulation of prohormone processing.
AB  - The processing of prohormones involves cleavage at specific basic amino acids by
      members of the subtilisin-like serine endoprotease family, followed by trimming
      of the COOH terminus by carboxypeptidase E. The enzymes are regulated by the
      intra-organelle ionic environment, through post-translational processing and by
      interaction with endogenous inhibitors. Much has been learned about their
      catalytic function and cell biology from in vitro gene transfer experiments using
      chimeric molecules and by site-directed mutagenesis. Further insight into their
      molecular properties and physiological function has been gained recently from the
      study of in vivo mutants.

PMID- 9572110
TI  - The processing of yeast pheromones.
AB  - Yeast provides an attractive system in which to study proprotein processing. Many
      of their processing events are remarkably similar to those in higher eukaryotes
      and their amenability to experimental manipulation permits approaches that are
      not always feasible in multicellular organisms. Analysing the biosynthesis of the
      yeast mating pheromones has been particularly rewarding and has provided insights
      into both the proteolytic aspects of processing and other post-translational
      events such as prenylation and carboxymethylation.

PMID- 9572109
TI  - Subtilisin-related serine proteases in the mammalian constitutive secretory
      pathway.
AB  - Proteolytic cleavage is a key step in the activation of many secreted proteins.
      Since the identification of the prototype yeast enzyme Kex2, seven subtilisin
      related serine proteases, together with a number of isoforms, have been
      identified in mammalian cells, five of which act within the constitutive
      secretory pathway. Overlapping expression patterns and substrate specificities
      complicate analysis but individual roles are beginning to emerge for some members
      of the group.

PMID- 9572111
TI  - Lateral asymmetry in multicellular organisms.

PMID- 9572112
TI  - Left-right development: mammalian phenotypes and conceptual models.
AB  - Consistent left-right asymmetry in a population requires a special kind of
      developmental specification. Models of this process must account for the complex
      phenotypes seen when left-right is abnormal. In some human and mouse mutations,
      there appears to be a randomisation of global situs to either solitus or
      inversus, whereas in the inv/inv mouse essentially all are inversus. However, in
      these and all additional examples there are frequently other anomalies, including
      symmetry (isomerism) and discordance between organs (heterotaxia). Current models
      invoke a molecular chiral referent as the source of the primary handed
      information. We describe a new two-gradient model which accommodates all defects
      of situs whilst leaving the primary asymmetry unaltered.

PMID- 9572113
TI  - The development of dorsoventral and bilateral axial properties in sea urchin
      embryos.
AB  - Sea urchin embryos have provided excellent material for experimental and
      molecular analyses of the processes of cell and axis specification during
      embryogenesis. These studies revealed the tremendous developmental plasticity of
      cells in early embryos and the roles that cell-cell interactions play in
      determining cell fates. Details concerning sea urchin development can be found in
      a number of excellent reviews. This review summarizes experimental and molecular
      studies relating to axis determination and cell fate specification in echinoid
      embryos. Correlations are drawn from research carried out on the development of
      axial systems in other organisms.

PMID- 9572114
TI  - Handed asymmetry in nematodes.
AB  - Like most animals, C. elegans and other nematodes exhibit several internal left
      right asymmetries with an essentially invariant (dextral) handedness. Handedness
      is established in early cleavage, resulting in a markedly left-right-asymmetric
      embryo on which bilateral symmetry must be superimposed later in embryogenesis.
      Some of the asymmetric cell interactions that accomplish this have been
      identified, but the mechanism that initially establishes dextral rather than
      sinistral handedness is not understood, in C. elegans or any other embryo.
      Analysis of mutations that result in reversal of handedness, such as spn-1 in C.
      elegans, should help elucidate this process. A model involving centriolar
      segregation is proposed as a possible mechanism for handedness choice.

PMID- 9572115
TI  - Left-right development in Xenopus and zebrafish.
AB  - One of the most striking features of the vertebrate body plan is that most
      exterior structures are bilaterally symmetric while many interior structures are
      left-right asymmetric. Left-right asymmetries are displayed in the heart, the
      circulatory, digestive and respiratory systems and in the central nervous system.
      A fundamental question in the study of all patterning events, including left
      right axis formation, is how does asymmetry arise from apparent symmetry. A
      second important question that is perhaps unique to the study of left-right
      development, is how does the left-right axis align with the asymmetries that
      develop along the orthogonal axes; dorsal-ventral and anterior-posterior. Recent
      experiments in Xenopus laevis and zebrafish address both of these questions and
      have identified signaling molecules and interactions with midline cells that
      regulate left-right development.

PMID- 9572116
TI  - Left-right asymmetry and the chick embryo.
AB  - Left-right (LR) asymmetry provides a fascinating example of the patterning of a
      major body axis during embryonic development. The chick embryo was the first
      system in which a molecular basis for left-right patterning was characterized,
      revealing that molecules known to play a role in other aspects of embryogenesis
      likewise are involved in the establishment of left-right asymmetry. The chick has
      been instrumental in the identification of a pathway of genes which regulate the
      sidedness of major body organs, as well as providing a basis for understanding
      laterality disturbances in twins. This review summarizes the advances in LR
      asymmetry which have been made in the chick system within the context of
      laterality research in general.

PMID- 9572117
TI  - Handed asymmetry in the mouse: understanding how things go right (or left) by
      studying how they go wrong.
AB  - All vertebrates have characteristic asymmetries along the left/right axis. The
      positioning of asymmetric visceral organs is highly conserved evolutionarily and
      disruptions in left/right patterning can lead to severe morphological defects,
      demonstrating the importance of regulation of left/right developmental
      asymmetries. Our understanding of vertebrate left/right pattern formation has
      been advanced by studying several mouse mutations which disrupt this process.
      These mutant mice have served as tools to help us to unravel the genetic pathways
      of left/right development. The identification and analysis of genes with
      asymmetric expression patterns has allowed us to begin to understand the
      mechanisms which regulate left/right development.

PMID- 9572118
TI  - Genetics of human left-right axis malformations.
AB  - Like all vertebrates, humans establish anatomic left-right asymmetry during
      embryogenesis. Variation from this normal arrangement (situs solitus) results in
      heterotaxy, expressed either as randomization (situs ambiguus) or complete
      reversal (situs inversus) of normal organ position. Familial heterotaxy occurs
      with autosomal dominant, recessive, and X-linked inheritance. All possible situs
      variants--solitus, ambiguus, inversus--can appear among some heterotaxy families.
      Positional cloning has led to the identification of a gene on the X chromosome
      responsible for some cases of human heterotaxy. In addition to their medical
      relevance, human studies provide a unique contribution to our understanding of
      left-right axis development among all vertebrates.

PMID- 9572119
TI  - Cardiac looping--an uneasy deal with laterality.
AB  - Cardiac looping is a key morphogenetic event in vertebrate heart development. In
      a complex progression, the linear heart tube adopts a sweeping rightward
      curvature, establishing an architecture for the multichambered organ it soon
      becomes. Looping is an asymmetric event, its rightward direction being determined
      by an embryonic left-right axial pathway. The dextral loop has been a vehicle for
      development of heart complexity during evolution, to the extent that in higher
      vertebrates and humans, heart structure and function is extremely susceptible to
      perturbations of laterality, which may be common. The first clues to genetic
      control of laterality and looping are now emerging. Key issues to resolve include
      the origin of laterality information in the embryo, the exact nature of the
      effector molecules that link laterality to looping and the intrinsic mechanisms
      that drive the looping process itself.

PMID- 9572120
TI  - Report of the NIH Panel to Define Principles of Therapy of HIV Infection.
AB  - Recent research advances have afforded substantially improved understanding of
      the biology of human immunodeficiency virus (HIV) infection and the pathogenesis
      of the acquired immunodeficiency syndrome (AIDS). With the advent of sensitive
      tools for monitoring HIV replication in infected persons, the risk of disease
      progression and death can be assessed accurately and the efficacy of anti-HIV
      therapies can be determined directly. Furthermore, when used appropriately,
      combinations of newly available, potent antiviral therapies can effect prolonged
      suppression of detectable levels of HIV replication and circumvent the inherent
      tendency of HIV to generate drug-resistant viral variants. However, as
      antiretroviral therapy for HIV infection has become increasingly effective, it
      has also become increasingly complex. Familiarity with recent research advances
      is needed to ensure that newly available therapies are used in ways that most
      effectively improve the health and prolong the lives of HIV-infected persons. To
      enable practitioners and HIV-infected persons to best use rapidly accumulating
      new information about HIV disease pathogenesis and treatment, the Office of AIDS
      Research of the National Institutes of Health sponsored the NIH Panel to Define
      Principles of Therapy of HIV Infection. This Panel was asked to define essential
      scientific principles that should be used to guide the most effective use of
      antiretroviral therapies and viral load testing in clinical practice. Based on
      detailed consideration of the most current data, the Panel delineated eleven
      principles that address issues of fundamental importance for the treatment of HIV
      infection. These principles provide the scientific basis for the specific
      treatment recommendations made by the Panel on Clinical Practices for the
      Treatment of HIV Infection sponsored by the Department of Health and Human
      Services and the Henry J. Kaiser Family Foundation. The reports of both of these
      panels are provided in this publication. Together, they summarize new dta and
      provide both the scientific basis and specific guidelines for the treatment of
      HIV-infected persons. This information will be of interest to health-care
      providers, HIV-infected persons, HIV/AIDS educators, public health educators,
      public health authorities, and all organizations that fund medical care of HIV
      infected persons.

PMID- 9572121
TI  - Guidelines for the use of antiretroviral agents in HIV-infected adults and
      adolescents. Department of Health and Human Services and Henry J. Kaiser Family
      Foundation.
AB  - With the development and FDA approval of an increasing number of antiretroviral
      agents, decisions regarding the treatment of HIV-infected persons have become
      complex; and the field continues to evolve rapidly. In 1996, the Department of
      Health and Human Services and the Henry J. Kaiser Family Foundation convened the
      Panel on Clinical Practices for the Treatment of HIV to develop guidelines for
      the clinical management of HIV-infected persons. This report includes the
      guidelines developed by the Panel regarding the use of laboratory testing in
      initiating and managing antiretroviral therapy, considerations for initiating
      therapy, whom to treat, what regimen of antiretroviral agents to use, when to
      change the antiretroviral regimen, treatment of the acutely HIV-infected person,
      special considerations in adolescents, and special considerations in pregnant
      women. Viral load and CD4+ T cell testing should ideally be performed twice
      before initiating or changing an antiretroviral treatment regimen. All patients
      who have advanced or symptomatic HIV disease should receive aggressive
      antiretroviral therapy. Initiation of therapy in the asymptomatic person is more
      complex and involves consideration of multiple virologic, immunologic, and
      psychosocial factors. In general, persons who have <500 CD4+ T cells per mm3
      should be offered therapy; however, the strength of the recommendation to treat
      should be based on the patient's willingness to accept therapy as well as the
      prognosis for AIDS-free survival as determined by the HIV RNA copy per mL of
      plasma and the CD4+ T cell count. Persons who have >500 CD4+ T cells per mm3 can
      be observed or can be offered therapy; again, risk of progression to AIDS, as
      determined by HIV RNA viremia and CD4+ T cell count, should guide the decision to
      treat. Once the decision to initiate antiretroviral therapy has been made,
      treatment should be aggressive with the goal of maximal viral suppression. In
      general, a protease inhibitor and two nucleoside [corrected] reverse
      transcriptase inhibitors should be used initially. Other regimens may be utilized
      but are considered less than optimal Many factors, including reappearance of
      previously undetectable HIV RNA, may indicate treatment failure. Decisions to
      change therapy and decisions regarding new regimens must be carefully considered;
      there are minimal clinical data to guide these decisions. Patients with acute HIV
      infection should probably be administered aggressive antiretroviral therapy; once
      initiated, duration of treatment is unknown and will likely need to continue for
      several years, if not for life. Special considerations apply to adolescents and
      pregnant women and are discussed in detail.

PMID- 9572122
TI  - UK biotech flagship meets stormy waters.

PMID- 9572123
TI  - Row erupts over child aggression study.

PMID- 9572124
TI  - Japan set to inject funds into endocrine disrupter research.

PMID- 9572125
TI  - German sex killings prompt decision to create a DNA database.

PMID- 9572126
TI  - Assessing risks of genetic engineering.

PMID- 9572127
TI  - Assessing risks of genetic engineering.

PMID- 9572128
TI  - Reaping the benefits of basic research.

PMID- 9572129
TI  - Cancer controversy.

PMID- 9572130
TI  - Ending up with the right partner.

PMID- 9572131
TI  - Biological sensors. Controlling the fly's gyroscopes.

PMID- 9572132
TI  - The evolution of menopause.

PMID- 9572133
TI  - Protein folding. Matching speed and locality.

PMID- 9572134
TI  - Spongiform encephalopathies. The prion's perplexing persistence.

PMID- 9572135
TI  - Scrapie infectivity found in resistant species.

PMID- 9572136
TI  - Asymmetric cell division.
AB  - With the recent identification of intrinsic cell-fate determinants for asymmetric
      cell division in several systems, biologists have begun to gain insight into the
      cellular mechanisms by which these determinants are preferentially segregated
      into one of the two daughter cells during mitosis so that the daughter cells
      acquire different fates.

PMID- 9572137
TI  - Biomimetic engineering of non-adhesive glycocalyx-like surfaces using
      oligosaccharide surfactant polymers.
AB  - The external region of a cell membrane, known as the glycocalyx, is dominated by
      glycosylated molecules, which direct specific interactions such as cell-cell
      recognition and contribute to the steric repulsion that prevents undesirable non
      specific adhesion of other molecules and cells. Mimicking the non-adhesive
      properties of a glycocalyx provides a potential solution to the clinical
      problems, such as thrombosis, that are associated with implantable devices owing
      to non-specific adsorption of plasma proteins. Here we describe a biomimetic
      surface modification of graphite using oligosaccharide surfactant polymers,
      which, like a glycocalyx, provides a dense and confluent layer of
      oligosaccharides. The surfactant polymers consist of a flexible poly(vinyl amine)
      with dextran and alkanoyl side chains. We show that alkanoyl side chains assemble
      on graphite through hydrophobic interaction and epitaxial adsorption. This
      constrains the polymer backbone to lie parallel to the substrate, with solvated
      dextran side chains protruding into the aqueous phase, creating a glycocalyx-like
      coating. The resulting biomimetic surface is effective in suppressing protein
      adsorption from human plasma protein solution.

PMID- 9572138
TI  - Reproductive cessation in female mammals.
AB  - In female mammals, fertility declines abruptly at an advanced age. The human
      menopause is one example, but reproductive cessation has also been documented in
      non-human primates, rodents, whales, dogs, rabbits, elephants and domestic
      livestock. The human menopause has been considered an evolutionary adaptation,
      assuming that elderly women avoid the increasing complications of continued
      childbirth to better nurture their current children and grandchildren. But an
      abrupt reproductive decline might be only a non-adaptive by-product of life
      history patterns. Because so many individuals die from starvation, disease and
      predation, detrimental genetic traits can persist (or even be favoured) as long
      as their deleterious effects are delayed until an advanced age is reached, and,
      for a given pattern of mortality, there should be an age by which selection would
      be too weak to prevent the onset of reproductive senescence. We provide a
      systematic test of these alternatives using field data from two species in which
      grandmothers frequently engage in kin-directed behaviour. Both species show
      abrupt age-specific changes in reproductive performance that are characteristic
      of menopause. But elderly females do not suffer increased mortality costs of
      reproduction, nor do post-reproductive females enhance the fitness of
      grandchildren or older children. Instead, reproductive cessation appears to
      result from senescence.

PMID- 9572139
TI  - Increased auditory cortical representation in musicians.
AB  - Acoustic stimuli are processed throughout the auditory projection pathway,
      including the neocortex, by neurons that are aggregated into 'tonotopic' maps
      according to their specific frequency tunings. Research on animals has shown that
      tonotopic representations are not statically fixed in the adult organism but can
      reorganize after damage to the cochlea or after training the intact subject to
      discriminate between auditory stimuli. Here we used functional magnetic source
      imaging (single dipole model) to measure cortical representations in highly
      skilled musicians. Dipole moments for piano tones, but not for pure tones of
      similar fundamental frequency (matched in loudness), were found to be enlarged by
      about 25% in musicians compared with control subjects who had never played an
      instrument. Enlargement was correlated with the age at which musicians began to
      practise and did not differ between musicians with absolute or relative pitch.
      These results, when interpreted with evidence for modified somatosensory
      representations of the fingering digits in skilled violinists, suggest that use
      dependent functional reorganization extends across the sensory cortices to
      reflect the pattern of sensory input processed by the subject during development
      of musical skill.

PMID- 9572140
TI  - Dynamic cortical activity in the human brain reveals motor equivalence.
AB  - That animals and humans can accomplish the same goal using different effectors
      and different goals using the same effectors attests to the remarkable
      flexibility of the central nervous system. This phenomenon has been termed 'motor
      equivalence', an example being the writing of a name with a pencil held between
      the toes or teeth. The idea of motor equivalence has reappeared because single
      cell studies in monkeys have shown that parameters of voluntary movement (such as
      direction) may be specified in the brain, relegating muscle activation to spinal
      interneuronal systems. Using a novel experimental paradigms and a full-head SQUID
      (for superconducting quantum interference device) array to record magnetic fields
      corresponding to ongoing brain activity, we demonstrate: (1), a robust
      relationship between time-dependent activity in sensorimotor cortex and movement
      velocity, independent of explicit task requirements; and (2) neural activations
      that are specific to task demands alone. It appears, therefore, that signatures
      of motor equivalence in humans may be found in dynamic patterns of cortical
      activity.

PMID- 9572141
TI  - Lipids are required for directional pollen-tube growth.
AB  - Successful pollination and fertilization are absolute requirements for sexual
      reproduction in higher plants. Pollen hydration, germination and penetration of
      the stigma by pollen tubes are influenced by the exudate on wet stigmas and by
      the pollen coat in species with dry stigmas. The exudate allows pollen tubes to
      grow directly into the stigma, whereas the pollen coat establishes the contact
      with the stigma. Pollen tubes then grow into the papillae, which are covered by a
      cuticle. The components of the exudate or pollen coat that are responsible for
      pollen tube penetration are not known. To discover the role of the exudate, we
      tested selected compounds for their ability to act as functional substitutes for
      exudate in the initial stages of pollen-tube growth on transgenic stigmaless
      tobacco plants that did not produce exudate. Here we show that lipids are the
      essential factor needed for pollen tubes to penetrate the stigma, and that, in
      the presence of these lipids, pollen tubes will also penetrate leaves. We propose
      that lipids direct pollen-tube growth by controlling the flow of water to pollen
      in species with dry and wet stigmas.

PMID- 9572142
TI  - Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe.
AB  - During meiotic prophase, chromosomes frequently adopt a bouquet-like arrangement,
      with their telomeres clustered close to the nuclear periphery. A dramatic example
      of this occurs in the fission yeast, Schizosaccharomyces pombe, where all
      telomeres aggregate adjacent to the spindle pole body (SPB). Nuclei then undergo
      rapid traverses of the cell, known as 'horsetail' movement, which is led by the
      SPB dragging telomeres and chromosomes behind. This process may initiate or
      facilitate chromosome pairing before recombination and meiosis. With the aim of
      identifying components involved in telomere structure and function, we report
      here the isolation of S. pombe mutants defective in the ability to impose
      transcriptional silencing on genes placed near telomeres. Two of these mutants,
      lot2-s17 and lot3-uv3, also display a dramatic lengthening of telomeric repeats.
      lot3-uv3 carries a mutation in Taz1, a telomere-binding protein containing a Myb
      like motif similar to two human telomere-binding proteins. Meiosis is aberrant in
      these mutant yeast strains, and our analysis demonstrates a decreased association
      of telomeres with the SPB in meiotic prophase. This results in defective
      'horsetail' movement, a significant reduction in recombination, low spore
      viability and chromosome missegregation through meiosis.

PMID- 9572143
TI  - Fission yeast Taz1 protein is required for meiotic telomere clustering and
      recombination.
AB  - The alignment of homologous chromosomes during meiosis is essential for their
      recombination and segregation. Telomeres form and protect the ends of eukaryotic
      linear chromosomes, and are composed of tandem repeats of a simple DNA sequence
      and the proteins that bind to these repeats. A role for telomeres in meiosis was
      suspected from observations of telomere clustering in meiotic cells, and has now
      been supported experimentally by the dramatic rearrangement of telomere locations
      during premeiotic stages in fission yeast. Here we show that the fission yeast
      telomere protein, Taz1, is required for stable association between telomeres and
      spindle pole bodies during meiotic prophase. In the absence of Taz1, telomere
      clustering at the spindle pole bodies is disrupted, meiotic recombination is
      reduced, and both spore viability and the ability of zygotes to re-enter mitosis
      are impaired to a level that would be expected if chromosome segregation were
      occurring randomly. Such telomeric association mediated by telomere-specific
      proteins may also be important for proper chromosome alignment and recombination
      during meiosis in humans.

PMID- 9572144
TI  - Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone
      H4 by RPD3.
AB  - The histone deacetylase RPD3 can be targeted to certain genes through its
      interaction with DNA-binding regulatory proteins. RPD3 can then repress gene
      transcription. In the yeast Saccharomyces cerevisiae, association of RPD3 with
      the transcriptional repressors SIN3 and UME6 results in repression of reporter
      genes containing the UME6-binding site. RPD3 can deacetylate all histone H4
      acetylation sites in cell extracts. However, it is unknown how H4 proteins
      located at genes near UME6-binding sites are affected, nor whether the effect of
      RPD3 is localized to the promoter regions. Here we study the mechanism by which
      RPD3 represses gene activity by examining the acetylation state of histone
      proteins at UME6-regulated genes. We used antibodies specific for individual
      acetylation sites in H4 to immunoprecipitate chromatin fragments. A deletion of
      RPD3 or SIN3, but not of the related histone-deacetylase gene HDA1, results in
      increased acetylation of the lysine 5 residue of H4 in the promoters of the UME6
      regulated INO1, IME2 and SPO13 genes. As increased acetylation of this residue is
      not merely a consequence of gene transcription, acetylation of this site may be
      essential for regulating gene activity.

PMID- 9572145
TI  - Structure of the calcium pump from sarcoplasmic reticulum at 8-A resolution.
AB  - The calcium pump from sarcoplasmic reticulum (Ca2+-ATPase) is typical of the
      large family of P-type cation pumps. These couple ATP hydrolysis with cation
      transport, generating cation gradients across membranes. Ca2+-ATPase specifically
      maintains the low cytoplasmic calcium concentration of resting muscle by pumping
      calcium into the sarcoplasmic reticulum; subsequent release is used to initiate
      contraction. No high-resolution structure of a P-type pump has yet been
      determined, although a 14-A structure of Ca2+-ATPase, obtained by electron
      microscopy of frozen-hydrated, tubular crystals, showed a large cytoplasmic head
      connected to the transmembrane domain by a narrow stalk. We have now improved the
      resolution to 8A and can discern ten transmembrane alpha-helices, four of which
      continue into the stalk On the basis of constraints from transmembrane topology,
      site-directed mutagenesis and disulphide crosslinking, we have made tentative
      assignments for these alpha-helices within the amino-acid sequence. A distinct
      cavity leads to the putative calcium-binding site, providing a plausible path for
      calcium release to the lumen of the sarcoplasmic reticulum.

PMID- 9572146
TI  - Three-dimensional map of the plasma membrane H+-ATPase in the open conformation.
AB  - The H+-ATPase from the plasma membrane of Neurospora crassa is an integral
      membrane protein of relative molecular mass 100K, which belongs to the P-type
      ATPase family that includes the plasma membrane Na+/K+-ATPase and the
      sarcoplasmic reticulum Ca2+-ATPase. The H+-ATPase pumps protons across the cell's
      plasma membrane using ATP as an energy source, generating a membrane potential in
      excess of 200mV. Despite the importance of P-type ATPases in controlling membrane
      potential and intracellular ion concentrations, little is known about the
      molecular mechanism they use for ion transport. This is largely due to the
      difficulty in growing well ordered crystals and the resulting lack of detail in
      the three-dimensional structure of these large membrane proteins. We have now
      obtained a three-dimensional map of the H+-ATPase by electron crystallography of
      two-dimensional crystals grown directly on electron microscope grids. At an in
      plane resolution of 8 A, this map reveals ten membrane-spanning alpha-helices in
      the membrane domain, and four major cytoplasmic domains in the open conformation
      of the enzyme without bound ligands.

PMID- 9572147
TI  - Mitochondrial genetics and hearing loss: the missing link between genotype and
      phenotype.
AB  - Mitochondrial DNA mutations have been implicated in a great variety of diseases,
      including such common ones as diabetes, Parkinson's disease and Alzheimer's, but
      the pathophysiological pathway leading from a specific mutation to a specific
      phenotype has remained elusive. Individuals with the same mutation can fall along
      a clinical spectrum ranging from asymptomatic to severely affected, and can even
      have completely different diseases. Much of this phenotypic heterogeneity has
      been attributed to the heteroplasmic nature of mitochondrial mutations, with both
      normal and mutated mitochondrial chromosomes being present in different
      proportions and tissue distributions. Isolated hearing loss is one of the only
      mitochondrial disorders that can be caused by homoplasmic mutations (e.g., only
      mutated mitochondrial mutations are present in all tissues). This review will
      outline the relationship between mitochondrial mutations and hearing loss while
      showing that even in a homoplasmic model, the two basic questions of
      mitochondrial genetics, penetrance and tissue specificity, remain unanswered: Why
      does the same mutation cause severe hearing loss in some family members but not
      in others, and why is the ear the only organ affected?

PMID- 9572148
TI  - Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological
      implications.
AB  - The pancreatic polypeptide (PP-fold) family of peptides consists of the endocrine
      peptides, pancreatic polypeptide (PP) and peptide YY (PYY), and the neuroneally
      derived peptide, neuropeptide Y (NPY). All three peptides are found in the
      circulation, with PP found primarily in the pancreas and PYY found principally in
      the gut. NPY is released into the circulation from neuroneal stores in response
      to stress. These peptides have broad peripheral actions on a number of organs.
      Not surprisingly, PYY and PP are believed to play an important role in the
      function of the gastrointestinal tract while NPY is a potent vasconstrictor and
      may have effects on the gut through the enteric nervous system. In the brain, NPY
      has been implicated in anxiety and depression, feeding and obesity, memory
      retention, neuroneal excitability, endocrine function, and metabolism. Recent
      advances in the molecular biology of the receptors for these peptides have
      resulted in the identification of at least six receptor subtypes with varying
      peptide pharmacology. Compared to other G-protein coupled receptor families, the
      PP-fold peptide receptors exhibit a relatively low level of sequence identity.
      Further advances in the development of selective agonists and antagonists for
      individual receptor subtypes will be needed to understand further their role in
      physiological function.

PMID- 9572149
TI  - Nonenzymatic glycation of collagen in aging and diabetes.

PMID- 9572150
TI  - Dietary fat type and level influence adiposity development in obese but not lean
      Zucker rats.
AB  - The development of obesity is influenced by a variety of factors including
      genetics and dietary fat type and level. To examine the interaction between these
      factors, male lean and obese Zucker rats (5 weeks initial age) were fed either a
      low-fat (15% calories) or one of two high-fat diets (65% calories; predominant
      fat source of either soybean oil or palm olein) for 8 weeks. Body weight, food
      intake, indirect calorimetry, and body composition determinations were performed.
      As expected, food intake, body weight, feed efficiency, oxygen consumption, heat
      production and carcass lipid were all significantly higher in obese compared to
      lean rats. Dietary fat level and/or type influenced body weight gain, oxygen
      consumption, heat production, energy balance, and carcass weight and lipid
      content in the obese but not in the lean Zucker rats. Oxygen consumption and
      carcass weight were increased approximately 25% and 10% respectively in obese
      rats fed either of the two high-fat diets as compared to those fed the low-fat
      diet. The type of fat fed in the high-fat diets also influenced body weight gain,
      heat production, energy balance, and carcass lipid content of the obese rats.
      Body weight gain and carcass lipid content were increased (16%-17%; P < 0.005) in
      obese rats fed the high-fat palm olein diet as compared to those fed the low-fat
      diet. These parameters were not increased in obese rats fed the high-fat soybean
      oil diet. In contrast, indirect calorimetry measurements indicated a moderate
      increase in heat production (Kcal/effective body mass/day; 14.5%) and decrease in
      energy balance (44.8%) in the obese rats fed the high-fat soybean oil diet as
      compared to those fed the low-fat diet. Energy expenditure and lipid accumulation
      were negligibly influenced by dietary fat level or type in the lean Zucker rats.
      The differential response of the lean and obese Zucker rats to this short-term
      dietary manipulation demonstrate that genetic background can influence an
      individual's response to dietary fat type and level. The genetically obese Zucker
      rat appears to be a good model for further studies of high-fat diet-induced
      obesity.

PMID- 9572151
TI  - Antiproliferative effects of inducible nitric oxide synthase inhibition on
      decidualization in pseudopregnant rats.
AB  - The aim of this study was to assess the involvement in decidual proliferation of
      nitric oxide (NO), a regulator of many cellular processes, that is synthesized
      from L-arginine by NO synthase. The investigation was conducted on pseudopregnant
      (PG) rats in which the decidual cell reaction, the basis for the decidualization
      process, was surgically induced by uterine trauma on PG Day 4. Groups of animals
      (n = 5) were pretreated with either 2 doses/day of N(G)-nitro-L-arginine methyl
      ester (L-NAME) that inhibits NO synthase, or twice daily doses of L-NAME plus L
      arginine combined. Drug application times coincided with 3 hr after lights on or
      3 hr before lights off. The two treatment regimens (PG Days 1-4 or 5-8)
      respectively preceded or followed decidual induction. Animals were sacrificed at
      mid-light on PG Day 9, the day of maximal growth response to the deciduogenic
      stimulus. Parallel, time-dependent increases in both NO synthase activity and
      decidual growth occurred mainly in the endometrium. L-NAME produced reductions in
      endometrial and myometrial growth that were reversed by the combined L-NAME plus
      L-arginine treatments. These inhibitory effects by L-NAME were caused by only the
      pretraumal (PG Days 1-4) administration. Hormonally, circulating progesterone
      levels were similarly affected by this early treatment and may also contribute to
      the reduced decidual sensitivity. In contrast, serum estradiol, along with the
      zinc metalloenzymes, alkaline phosphatase and the matrix metalloproteinases-
      prominent decidualization biomarkers--were all unaffected by either the pre- or
      post-decidual induction dosings. The study demonstrates that inducible NO
      synthase/endogenous NO may physiologically participate in uterine metabolism
      during the decidual cell reaction. Moreover, by virtue of L-NAME inhibition of
      the decidual response, it appears that NO synthase/NO may influence decidual
      growth either by directly increasing uterine sensitivity to the deciduogenic
      stimulus or by indirectly affecting endometrial vascularity and subsequent
      availability of decidual metabolites.

PMID- 9572152
TI  - Transforming growth factor beta 1 binding and receptor kinetics in fetal mouse
      lung fibroblasts.
AB  - TGFbeta1 inhibits fetal lung maturation in vitro. As TGFbeta1 is present in fetal
      lung, mechanisms must exist to overcome this inhibition and allow late gestation
      maturation to progress. We studied the ontogeny of TGFbeta1 binding, and TGFbeta
      receptor kinetics and subtypes in primary cultures of fetal mouse lung
      fibroblasts from Day 16 to Day 18 of gestation. TGFbeta1 specific binding in
      fetal lung fibroblasts declined with advancing gestation. The decrease occurred
      earlier, and was more pronounced in female fibroblasts (50% decrease) than in the
      male fibroblasts (29% decrease). Dihydrotestosterone treatment of Day 18 female
      fibroblasts resulted in a dose-dependent increase in TGFbeta1 binding. Scatchard
      analysis revealed a decline in receptor number with advancing gestation (Day 16
      female Bmax: 7.3 x 10(-16); Day 18 female Bmax: 5.5 x 10[-16]) whereas binding
      affinities remained constant. Affinity labeling followed by chemical cross
      linking and autoradiography showed the three known TGFbeta receptor subtypes at
      both Days 16 and 18 of gestation. The relative abundance of nonsignaling Type III
      receptors in comparison to signaling Type II and Type I receptors was increased
      at Day 18 versus Day 16. Incorporation of [3H]thymidine into DNA after treatment
      with TGFbeta1 changed from Day 16 to Day 18, consistent with changes previously
      reported between fetal and adult lung fibroblasts. We conclude that as fetal
      mouse lung maturation progresses, TGFbeta receptor number decreases in
      fibroblasts, the relative proportion of nonsignaling versus signaling receptor
      types increases, and the response to TGFbeta1 stimulation changes. These changes
      may contribute to overcoming TGFbeta1 inhibition of lung maturation.

PMID- 9572153
TI  - Changes in renal phosphate reabsorption in the aged rat.
AB  - Depletion of inorganic phosphate (Pi) reserves occurs frequently in aged animals
      and can result in diminished bone mineralization and osteoporosis. This altered
      Pi balance results from a reduction in intestinal Pi absorption and an elevation
      in renal Pi excretion. Since the kidney plays a central role in maintaining Pi
      homeostasis, we tested whether the increased phosphaturia seen with aging is a
      consequence of changes in the intrinsic tubular capacity to reabsorb Pi (TmPi).
      Male Wistar rats (12-, 18-, and 24-months-old) were acutely
      thyroparathyroidectomized (TPTX) and prepared for renal clearance studies in the
      presence and absence of fixed levels of parathyroid hormone (synthetic PTH-(1
      34), 1 U/kg/min). The maximum capacity for Pi transport (TmPi) was assessed by
      infusion of Pi at progressively higher rates (0-6 micromol/min) to increase the
      filtered load of Pi and facilitate the determination of the TmPi. TmPi declined
      significantly with age (3.51 +/- 0.12 vs 3.04 +/- 0.19 vs 2.30 +/- 0.18
      micromol/ml, for 12-, 18-, and 24-month-old rats, respectively, P < 0.05) in TPTX
      rats. Administration of PTH markedly reduced the TmPi in all age groups. Although
      the TmPi attained was similar among the age groups (1.15 +/- 0.13 vs 1.15 +/-
      0.06 vs 1.03 +/- 0.09 micromol/ml, for 12-, 18-, and 24-month-old rats,
      respectively), the magnitude of the reduction in the presence of PTH declined
      from 67% in 12-month-old rats to 62% and 55% in 18- and 24-month-old rats,
      respectively. These results demonstrate that aging is associated with a PTH
      independent decrease in the intrinsic capacity of the kidney to reabsorb
      phosphate. Further, the kidney of the aged rat can respond to a pharmacological
      dose of PTH with appropriate reductions in the TmPi although the magnitude of the
      response declines with age.

PMID- 9572154
TI  - Effects of immunoneutralization of substance P on hypothalamic neurotransmitters
      in normal mice and in transgenic mice expressing bovine growth hormone.
AB  - It is well known that transgenic mice expressing bovine growth hormone have
      altered neuroendocrine functions. Substance P was shown to influence the
      secretion of gonadotropins. In this investigation, the effect of a single
      injection of an antiserum to substance P was investigated in intact and castrated
      transgenic (MT-bGH) mice and in their normal litter mates. In the median
      eminence, the administration of antisubstance P serum resulted in a decreased
      dihydroxyphenyl acetic acid/dopamine index in intact and castrated normal mice
      but was without effect in transgenics. The homovanillic/dopamine index was
      decreased in normal mice (intact or castrated) but unchanged in transgenics.
      Norepinephrine and epinephrine were increased in normal mice (intact and
      castrated) treated with the anti-SP serum, but in transgenic mice, the anti-SP
      serum induced significant changes of norepinephrine only in intact animals, with
      no modifications in epinephrine levels. In the whole hypothalamus (minus the
      median eminence), the injection of antisubstance P serum resulted in an increased
      dihydroxyphenyl acetic acid/dopamine index in castrated, but not in intact,
      normal mice. In transgenic mice, this index was increased in intact but decreased
      in castrated animals. The homovanillic/dopamine index was decreased in normal
      intact mice treated with the antiserum but increased in intact transgenic mice.
      Norepinephrine and epinephrine were decreased by the antiserum treatment in
      normal intact mice but were unchanged in transgenics, except for norepinephrine
      in castrated transgenics, in which it was found increased. The administration of
      the antiserum did not affect plasma LH, FSH, or prolactin in normal mice but it
      reduced LH levels in intact transgenic mice. These results indicate that the
      response to the treatment with the antiserum to substance P shows considerable
      alterations in transgenic mice as compared with their litter-mate, normal
      controls, producing divergent effects on hypothalamic catecholamine metabolism.
      The present findings confirm that transgenic mice overexpressing the bGH gene
      have marked neuroendocrine alterations as compared with their normal litter
      mates.

PMID- 9572155
TI  - Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin
      (MLT) supplementation of old mice.
AB  - Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone
      (DHEA) decline with age, and this decline is correlated with immune dysfunction.
      The aim of the current study is to determine whether hormone supplementation with
      MLT and DHEA together would synergize to reverse immune senescence. Old (16.5
      months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As
      expected, splenocytes were significantly (P < 0.05) higher in old mice as
      compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005)
      increased B cell proliferation in young mice. However, only MLT and DHEA + MLT
      significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT,
      and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by
      significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-gamma or
      significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus
      regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1
      cytokine and elevated Th2 cytokine production; however, their combined use
      produced only a limited additive effect.

PMID- 9572156
TI  - Absence of mycoplasmal gene in malignant mammalian cells transformed by chronic
      persistent infection of mycoplasmas.
AB  - Chronic persistent infections by mycoplasmas induced malignant transformation of
      C3H mouse embryo cells that normally had never been reported to undergo
      spontaneous transformation. This mycoplasma-mediated oncogenic process had a long
      latency (more than 7 weeks of continuous mycoplasmal infection) and showed a
      multistage progression characterized by reversibility (at least up to 11 weeks of
      mycoplasmal infection) and irreversibility of malignant properties upon removal
      of the mycoplasma from culture. Further prolonged infections (18 weeks) by
      Mycoplasma fermentans or M. penetrans resulted in permanent transformation of
      these C3H cells that no longer required the continued presence of the
      transformation-inducing mycoplasmas in cultures to retain their malignant
      properties. Previous studies of viral oncogenesis revealed that virus-transformed
      cells always had viral gene(s) present. Integration of viral gene(s) apparently
      played an important role in the process of oncogenesis. In this study, we
      examined if the continued presence of any mycoplasmal gene(s) in mammalian cells,
      in whatever form, was also crucial in causing malignant cell transformation.
      Representational difference analysis (RDA) was a recently developed powerful
      technique to compare differences between two complex genomes. In the RDA system,
      subtractive and kinetic enrichment was used to purify and isolate restriction
      endonuclease gene fragment(s) of mycoplasmal origin, presumably present only in
      mycoplasma-transformed C3H cells, but not in nonmycoplasma-exposed control C3H
      cells. After three rounds of subtractive hybridization following PCR enrichment
      for each of three different restriction enzymes DNA digests, no gene fragment of
      mycoplasmal origin was amplified or identified in the permanently transformed C3H
      cells. Differing from tumorigenesis in animal cells induced by most oncogenic
      viruses or in plant cells induced by Agrobacteria, mycoplasmas evidently did not
      cause malignant transformation by integrating their gene(s) into the mammalian
      cell genome.

PMID- 9572157
TI  - Consumption of fatty fish from the Baltic Sea and PCB in whole venous blood,
      plasma and cord blood from delivering women in the Aland/Turku archipelago.
AB  - The present study aimed to assess the role of fish consumption for the body
      burden of polychlorinated biphenyls (PCBs) in mothers living in the Aland and
      Turku archipelago in Finland. The overall objective was to investigate whether
      there exists an appropriate population for a full-scale prospective study on PCB
      related developmental effects in infants. Concentrations of the four major PCBs
      were determined in whole venous blood and cord blood from 30 delivering mothers,
      of which 20 subjects consumed fatty fish from the Baltic Sea (2.5-12.5 meals per
      month) and the remaining 10 mothers did not. The concentrations of CB-118, CB
      138, CB-153, and CB-180 in cord blood were generally two- to threefold lower than
      in whole blood from the mothers, but strong correlations were observed between
      PCBs in the two matrices (r = .67-.80). Neither the venous blood nor cord blood
      concentrations of PCBs, however, were correlated with stated fish intake.
      Moreover, the concentration of CB-153 in plasma was only weakly associated with
      fish intake, and the level of organic mercury in erythrocytes was not correlated
      with fish intake at all. The present results of CB-153 concentrations in women's
      blood are lower than those reported in other recent investigations. A reasonable
      contributing explanation is the rapid decline during the last decades of PCB in
      Baltic Sea fish, which has resulted in less impact of fish intake on the body
      burdens of PCB in relatively young women (median 30 yr in the present study) as
      compared with older females. The relatively low PCB levels in blood taken
      together with the low number of yearly deliveries in the archipelago population
      makes it an inappropriate study base for a prospective study of PCB-related
      health effects in infants.

PMID- 9572158
TI  - Effects of silica exposure on substance P immunoreactivity and preprotachykinin
      mRNA expression in trigeminal sensory neurons in Fischer 344 rats.
AB  - Trigeminal sensory neurons innervate the nasal cavity and may release substance P
      (SP) upon exposure to inhaled irritants. The purpose of this study was to
      determine if silica dust, an occupational irritant causing inflammation,
      activates sensory neurons supplying the nasal cavity. Male Fischer 344 rats were
      placed in inhalation chambers and exposed daily to 2 mg/m3 of fresh silica
      (average diameter 1 microm) for 6 mo. Following exposure, the trigeminal ganglia
      (TG) were removed and prepared for SP immunocytochemistry and for
      preprotachykinin (PPT) autoradiographic in situ hybridization. The SP-like
      immunofluorescence in TG neurons was subjectively categorized as high, moderate,
      or low (background) intensity. In situ hybridization autoradiographs were
      quantified on the basis of grain density using digital imaging analysis. The SP
      immunoreactivity and PPT mRNA expression in the TG neurons were significantly
      increased after silica inhalation. The proportion of highly positive SP
      immunoreactive neurons shifted from 1.30 +/- 0.58% in controls to 11.30 +/- 1.15%
      after silica treatment. The neurons exhibiting high grain density for PPT mRNA
      increased from 1.50 +/- 0.87% in controls to 11.67 +/- 0.58% in the silica group.
      Thus, inhalation of silica causes upper airway irritation resulting in increased
      levels of immunoreactive neuronal SP and PPT mRNA. These findings suggest that
      silica activates sensory pathways that may be involved in nasal inflammation.

PMID- 9572159
TI  - Potential teratogenicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone
      (MX) in micromass in vitro test.
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a by-product of wood
      pulp manufacture and a contaminant of chlorinated drinking water, was
      investigated for potential teratogenicity using the micromass in vitro test
      system. Twelve-day rat embryo midbrain (central nervous system, CNS) and limb bud
      (LB) cells were exposed to MX at concentrations of 1, 2, 5, or 10 microg/ml in
      the culture medium with or without S9 mix. Under the experimental conditions, the
      amount of MX rapidly declined in the culture medium with a half-life of 56 min.
      Nevertheless, differentiation of CNS and LB cells was significantly inhibited at
      concentrations of 2 microg/ml or more, when the cells were exposed to MX in the
      absence of S9 mix. The estimated IC50 was approximately 3 microg/ml for both CNS
      and LB cell cultures. On the other hand, exposure of CNS and LB cells to MX along
      with S9 mix did not reduce the number of differentiated foci at any
      concentrations tested. These results suggest that MX may be a potential direct
      acting in vitro teratogen.

PMID- 9572160
TI  - Intestinal handling of mercury in the rat: implications of intestinal secretion
      of inorganic mercury following biliary ligation or cannulation.
AB  - Three sets of experiments were carried out to determine if there is an intestinal
      secretory component in the fecal excretion of administered inorganic mercury. In
      the first set of experiments the disposition of a nontoxic 0.5-micromol/kg
      intravenous dose of inorganic mercury was evaluated in control rats and rats
      whose bile duct had been ligated. Data collected 24 h after the administration of
      mercuric chloride indicated that some inorganic mercury had moved from the blood
      across the epithelium into the lumen of the stomach, small intestine, and large
      intestine. This secretory movement of mercury was most prominent in the small
      intestine. Interestingly, the renal uptake and accumulation of mercury were
      diminished significantly in the rats whose bile duct had been ligated. A time
      course experiment showed that the maximum amount of secretory movement of mercury
      into the lumen of the small intestine occurred during the initial 12 h after the
      injection of mercuric chloride. By the end of 24 h after the injection of
      mercuric chloride, much of the inorganic mercury secreted in the small intestine
      appeared to have moved down into the large intestine. In a third experiment, the
      disposition of mercury was evaluated in control rats and rats who had their bile
      duct cannulated. The rationale for this third experiment was to study the
      disposition of mercury under conditions where obstruction of biliary outflow from
      the liver would not be as much of an issue as with ligation of the bile duct.
      Evidence for movement of mercury into the lumen of the intestines was also
      obtained from the rats whose bile duct had been ligated. Eighteen hours after the
      injection of mercuric chloride the amount of mercury in the luminal compartment
      of the small intestine was not statistically different between the two groups of
      rats. Approximately 1.7-2.1% of the administered dose was present in the luminal
      contents of the small intestine. Decreased renal uptake of mercury was also
      detected in the rats whose bile duct had been cannulated. The findings from the
      present study show that when bile flow is obstructed or diverted, clear evidence
      for secretory movement of mercury into the lumen of the gastrointestinal (GI)
      tract can be demonstrated. These findings also indicate that the secretory
      movement of mercury into the lumen of the GI tract is a mechanism that
      contributes significantly to the pool of mercury that is excreted in the feces.

PMID- 9572161
TI  - Lipid peroxidation and antioxidant status in the liver, erythrocytes, and serum
      of rats after methanol intoxication.
AB  - Lipid peroxidation products measured as a malondialdehyde and activities of
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione
      reductase (GSSG-R), and concentrations of ascorbic acid, alpha-tocopherol, and
      glutathione (GSH) were measured in the liver, erythrocytes, and serum of rats 6,
      14, and 24 h and 2, 5, and 7 d after treatment with 3 g methanol/kg. GSH-Px and
      GSSG-R activities, GSH level, and ascorbate concentration in the liver,
      erythrocytes, and blood serum were significantly decreased. In addition, SOD and
      alpha-tocopherol in erythrocytes were diminished, while malondialdehyde (MDA) in
      liver, erythrocytes, and serum were elevated. Further, erythrocyte counts,
      hemoglobin levels, hematocrit, and mean corpuscular volume (MCV) were reduced.
      These results indicate that methanol intoxication in rats leads to an increase in
      the lipid peroxidation and impairment in the antioxidant mechanisms in liver,
      erythrocytes, and blood serum.

PMID- 9572162
TI  - Glutathione S-conjugate formation and metabolism in HepG2 cells: a cell model of
      mercapturic acid biosynthesis.
AB  - Mercapturic acid biosynthesis is mediated by a series of at least four enzymatic
      steps and three cell membrane transport events, and is believed to require the
      interorgan shuttling of the various metabolic intermediates. To identify a single
      cell type that can carry out all of these metabolic and transport steps, the
      present study examined whether HepG2 cells, a human hepatoma-derived cell line,
      can convert an electrophilic chemical (1-chloro-2,4-dinitrobenzene, CDNB) to its
      corresponding mercapturic acid (S-dinitrophenyl-N-acetylcysteine, DNP-NAC). The
      results demonstrate that HepG2 cells are able to convert CDNB to DNP-NAC in a
      dose- and time-dependent fashion. Intracellular conjugation with glutathione
      occurred rapidly, and the resulting glutathione S-conjugate was promptly
      transported into the culture medium, where it was sequentially degraded to the
      cysteinylglycine and cysteine S-conjugates. The cysteine conjugate was then
      presumably reabsorbed, and N-acetylated intracellularly to form the mercapturic
      acid. The mercapturic acid was found to accumulate slowly in the culture medium,
      such that after 4 h of incubation, 4-10% of the CDNB dose was recovered as the
      mercapturic acid. These data provide the first demonstration that a single cell
      type can carry out all of the transport and enzymatic steps required for
      mercapturic acid biosynthesis. HepG2 cells may provide a useful model system for
      studying this important detoxification pathway.

PMID- 9572163
TI  - Association between cancer mortality and residence near petrochemical industries
      in Taiwan.

PMID- 9572165
TI  - Prenatal sonographic findings associated with sporadic subcortical nodular
      heterotopia.
AB  - BACKGROUND: Subcortical nodular heterotopia is a neuronal migration disorder of
      uncertain etiology. This disorder occurs primarily in females and has a familial
      X-linked dominant inheritance pattern. The predominant symptom associated with
      heterotopia is seizures. CASE: At 23 weeks' gestation, prenatal sonography
      disclosed an isoechoic supratentorial intracranial mass causing right-sided shift
      of midline structures and compression of the contralateral cerebral ventricle.
      Serial ultrasound examinations of this mass were significant for the absence of
      invasion into surrounding structures, gross enlargement of cranial biometric
      parameters, and hydrocephalus and hydrops fetalis. Neonatal magnetic resonance
      imaging findings were consistent with gray matter heterotopia and were confirmed
      as such by brain biopsy. CONCLUSION: Subcortical nodular heterotopia manifested
      unique prenatal sonographic findings. This case suggests the possibility of
      prenatal diagnosis in families at risk for this lesion.

PMID- 9572164
TI  - Hemodynamic changes with paradoxical blood flow in expectant management of
      abruptio placentae.
AB  - BACKGROUND: Because the early diagnosis of abruption often is missed or
      misinterpreted, emergency situations frequently do not permit adequate
      management. CASE: A woman of 26-weeks' gestation was transferred with symptoms
      and laboratory findings typical for abruption. Ultrasound, including Doppler,
      revealed a subchorionic hematoma, pathologic blood flow in the uterine arteries,
      low pulsatility index values in the fetal cerebral and umbilical arteries
      (paradoxical blood flow), and high maximal velocities in the fetal aorta.
      Repeated Doppler and laboratory examinations revealed a gradual restoration to
      normal of the arterial uterine blood flow pattern, of paradoxical blood flow,
      aortic maximal velocities, and laboratory values. CONCLUSION: Serial Doppler
      measurements considering the paradoxical pattern illustrate pathophysiologic
      mechanisms of abruption that may assist in deciding whether to deliver
      immediately or to continue intense surveillance.

PMID- 9572166
TI  - Prenatal ultrasound diagnosis of small-bowel torsion.
AB  - BACKGROUND: We report a case of congenital small-bowel torsion detected by
      prenatal ultrasonographic examination. CASE: A 27-year-old primigravida was found
      to have a fetus with a small-bowel obstruction by ultrasound examination during
      the third trimester. At 35 weeks of gestation, she complained of absence of fetal
      activity. A nonstress test showed a nonreactive pattern with reduced baseline
      variability. Sonographic examination revealed heterogeneous echogenicity within
      the dilated bowel, and loss of peristalsis. Also noted was a small amount of
      fetal ascites. After birth, torsion of the dilated small bowel associated with
      ileal atresia was found at exploratory laparotomy. CONCLUSION: Serial sonographic
      examinations with special attention to changes in the dilated bowel are useful in
      the management of prenatally diagnosed small-bowel obstruction.

PMID- 9572167
TI  - Aplastic anemia and immune-mediated thrombocytopenia: concurrent complications
      encountered in the third trimester of pregnancy.
AB  - BACKGROUND: Aplastic anemia has been described rarely in pregnancy. The etiology
      is uncertain, and the treatment of choice, bone marrow transplant, is
      contraindicated in pregnancy. Thus, the occurrence of this complication during
      gestation presents a management challenge. Concurrent immune-mediated
      thrombocytopenia further complicates an already complex situation. CASE: Our
      patient with aplastic anemia and immune-mediated thrombocytopenia was diagnosed
      during the third trimester of pregnancy and treated with prednisone/high-dose
      intravenous (i.v.) immunoglobulin (Ig) and multiple transfusions of packed red
      blood cells and platelets. Fetal surveillance included twice-weekly non-stress
      tests coupled with sequential sonographic pregnancy evaluation. A successful term
      vaginal delivery was achieved with good maternal and perinatal outcomes.
      CONCLUSION: Selective transfusion of blood products, therapy with prednisone,
      high-dose i.v. Ig, and intensive fetal surveillance resulted in a successful
      maternal and perinatal outcome for a pregnancy complicated with aplastic anemia
      and immune-mediated thrombocytopenia.

PMID- 9572168
TI  - Acute fatty liver of pregnancy in triplet gestation.
AB  - BACKGROUND: Acute fatty liver is reported to be more common in twin than in
      singleton pregnancies. We report three cases of biopsy-proven acute fatty liver
      in triplet gestations. CASES: In all three cases of acute fatty liver
      complicating triplet pregnancies, the presenting features were vague abdominal
      complaints with elevated hepatic aminotransferase levels. A liver biopsy was
      performed in each case, and cesareans were performed immediately after the
      diagnosis was confirmed histologically. Clinical resolution occurred in all
      cases, and all infants did well in the neonatal period. CONCLUSION: Patients with
      triplet gestations should be monitored closely for the early signs of acute fatty
      liver. Triplet gestations may contribute to the onset of acute fatty liver by
      further stressing the fatty acid oxidation capabilities of the susceptible woman.

PMID- 9572169
TI  - Delayed diagnosis of bowel infarction secondary to maternal midgut volvulus at
      term.
AB  - BACKGROUND: Intestinal volvulus is responsible for 25% of acute bowel
      obstructions in pregnant women but only 3-5% in nonpregnant patients. Pregnancy
      may hinder early diagnosis. CASE: A woman in early labor subsequently developed
      hypotension and a nonreassuring fetal heart rate tracing. Emergency cesarean was
      performed and a live infant was born. At surgery, the patient was noted to have
      ascites, necrotic bowel, and a congenital gut malrotation with a complete midgut
      volvulus. Several congenital peritoneal bands were lysed, the volvulus was
      reduced, and 184 cm of small bowel were resected. CONCLUSION: This patient
      represents a case of midgut volvulus with bowel infarction and necrosis secondary
      to congenital malrotation of the gut.

PMID- 9572170
TI  - Cortical blindness and Anton syndrome in a patient with obstetric hemorrhage.
AB  - BACKGROUND: Cortical blindness is characterized by loss of vision in the presence
      of intact anterior visual pathways. Anton syndrome, a form of anosognosia, is a
      rare complication of cortical blindness involving compromise of the visual
      association centers, with resulting patient denial of blindness. Both syndromes
      have been associated with computed tomography findings of localized cortical
      ischemia. In most cases, both the clinical and radiologic features are
      reversible. CASE: A woman with hemorrhage from an incomplete abortion at 21 weeks
      experienced cortical blindness and visual anosognosia. CONCLUSION: Cortical
      blindness and anosognosia are unusual manifestations of severe hemorrhage but
      should be considered in the differential diagnosis of a patient with atypical
      visual symptoms.

PMID- 9572171
TI  - Severe preeclampsia associated with coinheritance of factor V Leiden mutation and
      protein S deficiency.
AB  - BACKGROUND: Inherited thrombophilic disorders are associated with an increased
      risk of venous thromboembolism during pregnancy. Preliminary research suggests
      that these disorders might also increase the risk for preeclampsia. CASE: A 29
      year-old primigravida developed severe, early onset preeclampsia and postpartum
      deep venous thrombosis. Subsequent testing revealed coinheritance of the factor V
      Leiden mutation and protein S deficiency. Heparin prophylaxis was administered
      during two subsequent pregnancies without recurrence of either preeclampsia or
      venous thromboembolism. CONCLUSION: Our patient's inherited thrombophilia may
      have played a role in the development of preeclampsia, and anticoagulation during
      subsequent pregnancies may have prevented preeclampsia recurrence. An association
      between inherited thrombophilic disorders and preeclampsia is biologically
      plausible.

PMID- 9572172
TI  - Iatrogenic monoamniotic twins as a complication of therapeutic amniocentesis.
AB  - BACKGROUND: Therapeutic amniocentesis has been accepted widely as a safe and
      efficacious way to treat the polyhydramnios-oligohydramnios sequence associated
      with twin-twin transfusion syndrome. CASE: A 28-year-old woman, gravida 2, para
      1, diagnosed with twin-twin transfusion syndrome at 28 weeks' gestation was
      treated with serial amniocenteses. The dividing membrane was ruptured
      inadvertently during therapeutic amniocentesis, with subsequent complete
      disruption of the amniotic membrane. Iatrogenic monoamniotic twins with cord
      entanglement and knotting resulted. CONCLUSION: Creation of monoamniotic twins by
      disruption of the dividing membrane can be a complication of therapeutic
      amniocentesis for twin-twin transfusion syndrome. Such disruption may result in
      the same morbidity and mortality that are seen in naturally occurring
      monoamniotic twins.

PMID- 9572173
TI  - Differential transmission of adenovirus in a twin pregnancy.
AB  - BACKGROUND: Intrauterine adenovirus infection has been associated with nonimmune
      hydrops. We describe a twin pregnancy in which adenovirus was demonstrated by
      polymerase chain reaction in the amniotic fluid of one twin afflicted by hydrops.
      Adenovirus was absent in the amniotic fluid of the other twin. CASE: A 25-year
      old, gravida 3, para 1, with twin gestation at 20 weeks' gestation was noted on
      ultrasound anomaly screen to have hydrops associated with twin B. Polymerase
      chain reaction analysis of amniotic fluid revealed adenovirus in twin B with none
      noted in twin A. At 26 weeks' gestation both infants died. CONCLUSION: This case
      demonstrates differential transmission of adenovirus in a twin pregnancy. One
      twin developed hydrops fetalis possibly secondary to adenovirus infection.

PMID- 9572174
TI  - Treatment of acardiac twinning.
AB  - BACKGROUND: The twin reversed-arterial-perfusion sequence is a complication of
      monochorionic twin pregnancies characterized by the hemodynamic dependence of a
      "recipient" twin from a "pump" twin. The recipient twin exhibits lethal
      abnormalities including acardia and acephaly. The pump twin has a mortality rate
      of 50% as a result of high-output heart failure. CASE: The blood supply to an
      acardiac-acephalus twin was interrupted at 24 weeks' gestation using endoscopic
      laser coagulation. The co-twin was delivered at 35 weeks and had an uneventful
      neonatal course following correction of a persistent patent ductus arteriosus.
      Review of the literature reveals 22 cases of acardiac twinning treated with
      invasive procedures, seven of them using endoscopic laser coagulation. Pump twin
      mortality with fetal surgery was 13.6% in comparison with 50% mortality with
      expectant management (P < .001). CONCLUSION: Fetal surgery is the best available
      treatment for acardiac twinning. Endoscopic laser coagulation at or before 24
      weeks and endoscopic or sonographic guided umbilical cord ligation after this
      gestational age seem to be the best treatments for this condition.

PMID- 9572175
TI  - Pretreatment of gastroschisis with transabdominal amniotic fluid exchange.
AB  - BACKGROUND: Intestinal thickening in gastroschisis results from prolonged
      exposure to amniotic fluid (AF). Experimental AF exchange has been shown to
      prevent intestinal thickening in gastroschisis. CASE: A 25-year-old primigravida
      was referred at 24 weeks' gestation with a prenatal diagnosis of gastroschisis.
      Transabdominal AF exchange was performed at 29 weeks. This pretreatment did not
      cause any complications and prevented intestinal thickening in our patient. Thus,
      we were able to perform primary fascial closure with an intra-abdominal pressure
      less than 5 mmHg. We began feeding the infant on the 5th day and discharged her
      on the 8th day. CONCLUSION: Evidence obtained from this initial case seems
      promising for the further application of the AF exchange for prevention of
      intestinal thickening in gastroschisis.

PMID- 9572176
TI  - Fetal tissue typing in anticipation of neonatal heart transplantation.
AB  - BACKGROUND: Hypoplastic left heart syndrome is among the most common major
      congenital cardiac anomalies. Fetuses with this anomaly survive but require
      either reconstructive surgery or heart transplantation postnatally. CASE: A woman
      whose fetus was diagnosed with hypoplastic left heart syndrome underwent
      funipuncture for fetal tissue typing. The fetus then was listed for heart
      transplantation. Once an ABO-compatible donor heart was procured, the fetus was
      delivered and immediately underwent transplantation. CONCLUSION: In candidates
      for neonatal heart transplantation, fetal tissue typing allows the search for an
      ABO-compatible donor heart to begin earlier. This approach minimizes the
      morbidity associated with postnatal waiting and allows transplantation to take
      place while the neonate is less immunocompetent.

PMID- 9572177
TI  - Complications of intrauterine placement of a vesicoamniotic shunt.
AB  - BACKGROUND: Fetal obstructive uropathies complicated by severe oligohydramnios
      can cause neonatal death due to renal dysplasia and pulmonary hypoplasia. CASE: A
      31-year-old multigravida was referred at 19.6 weeks with sonographic evidence of
      fetal megacystis and bilateral hydroureteronephrosis, and severe oligohydramnios.
      A vesicoamniotic shunt was placed for urinary diversion. Complications included
      shunt migration, intestinal evisceration, amniorrhexis, preterm labor, and
      preterm delivery. Bowel characteristics were assessed by measuring the intestinal
      lumen diameter for evidence of obstruction. The lumen diameter remained stable at
      3-5 mm, and the luminal wall remained stable at 2.5 mm. After birth at 31 weeks,
      the infant underwent exploratory laparotomy and extraction of malpositioned
      shunts, vesicostomy, and closure of abdominal wall defect. He was discharged at
      61 days of life after resolution of neonatal pulmonary and infectious
      complications. CONCLUSION: Operative management of complete fetal obstructive
      uropathy is beneficial despite potential complications.

PMID- 9572178
TI  - Disruption of prior uterine incision following misoprostol for labor induction in
      women with previous cesarean delivery.
AB  - BACKGROUND: Although induction of labor in women with prior cesareans is
      controversial, we compared misoprostol to oxytocin in such women in a randomized
      trial. The investigation was terminated prematurely because of safety concerns.
      CASES: Disruption of the prior uterine incision was found in two of 17
      misoprostol-treated women. The first woman underwent repeat cesarean delivery at
      42 weeks because of fetal tachycardia and repetitive late decelerations. A 10-cm
      vertical rent in the anterior myometrium was discovered. The second woman
      underwent induction for fetal growth restriction. Loss of fetal heart tones and
      abnormal abdominal contour prompted emergent cesarean for suspected uterine
      rupture. An 8-cm longitudinal uterine defect was found. CONCLUSION: When
      misoprostol is used in women with previous cesareans, there is a high frequency
      of disruption of prior uterine incisions.

PMID- 9572179
TI  - Common peroneal neuropathy secondary to squatting during childbirth.
AB  - BACKGROUND: Common peroneal neuropathy occurs fairly frequently in the adult
      population; however, very few cases of peroneal neuropathy after prolonged
      squatting have been reported. CASE: A 29-year-old woman noted right foot numbness
      and weakness immediately after childbirth, which involved 15-30 minutes of
      pushing in a squatting position. Physical examination and an electrodiagnostic
      study confirmed a common peroneal neuropathy. The patient was referred for
      rehabilitation, including bracing and gait training, which improved substantially
      her mobility and function. CONCLUSION: Prolonged squatting should be minimized or
      avoided. A high index of suspicion for peroneal neuropathy after prolonged
      squatting must be present. Early diagnosis and treatment may limit the number of
      complications in these patients, particularly falls.

PMID- 9572180
TI  - Atraumatic fetal cervical spinal cord injury and cruciate paralysis.
AB  - BACKGROUND: Congenital cervical spinal cord injury usually is attributed to
      intrapartum mechanical trauma. CASE: A fetal cervical spinal cord hemorrhage
      presented as congenital isolated upper extremity ("cruciate") paralysis and
      muscle atrophy after an atraumatic delivery. Timely neonatal diagnosis and
      surgery resulted in complete recovery. CONCLUSION: Paralysis may result from
      atraumatic spinal cord injuries occurring in the antepartum period.

PMID- 9572181
TI  - Pyoderma gangrenosum following cesarean delivery.
AB  - BACKGROUND: Pyoderma gangrenosum is a rare, chronic inflammatory disease that can
      develop after minor trauma or surgery. Most reports of this condition developing
      after abdominal surgery have been reported following ostomy formation. A number
      of systemic diseases have been associated with this disorder, most commonly
      inflammatory bowel disease, though 40-50% of cases have no associated systemic
      disease. CASE: A 32-year-old woman developed spiking fever and purulent appearing
      wound discharge with a rolled erythematous border after cesarean delivery. Her
      condition worsened despite various regimens of intravenous antibiotics and local
      treatment. Pyoderma gangrenosum was diagnosed. Treatment with steroids resolved
      the lesion, and associated systemic diseases were not found. CONCLUSION:
      Consideration of the diagnosis of pyoderma gangrenosum in cases of apparent wound
      infections unresponsive to antibiotics should result in early diagnosis and
      treatment of this condition.

PMID- 9572182
TI  - Ectopic pregnancy causing hemothorax managed by thoracoscopy and actinomycin D.
AB  - BACKGROUND: Most patients with extratubal ectopic pregnancies present with
      vaginal bleeding and lower abdominal pain. We report a case of an extratubal
      ectopic pregnancy with extra-abdominal manifestations. CASE: An ectopic pregnancy
      implanted on the diaphragm resulted in spontaneous hemothorax due to
      trophoblastic invasion into the pleura. Thoracoscopic excision followed by
      actinomycin D chemotherapy provided successful resolution of the ectopic
      pregnancy. CONCLUSION: Abdominal pregnancies may have bizarre clinical
      presentations.

PMID- 9572183
TI  - Cesarean scar pregnancy: imaging and treatment with conservative surgery.
AB  - BACKGROUND: Pregnancy in a cesarean scar represents a rare type of secondary
      abdominal pregnancy. Early diagnosis can be challenging and optimal treatment is
      unknown. CASE: A 21-year-old woman presented for an abortion at 8 weeks'
      gestation. A cesarean delivery had been performed 5 months earlier. Suspecting a
      cervical pregnancy, her physician referred her to us, and an 8-week cesarean scar
      gestation was diagnosed and then confirmed by serial sonograms, cystoscopy, and
      magnetic resonance imaging. The patient elected pregnancy termination, which was
      accomplished by hysterotomy with uterine preservation followed by intramuscular
      methotrexate. CONCLUSION: We report a case of cesarean scar pregnancy treated
      surgically with uterine preservation. This approach should be considered when
      cesarean scar ectopic pregnancy is diagnosed.

PMID- 9572184
TI  - Gallstones presenting as a cul-de-sac mass.
AB  - BACKGROUND: Pelvic masses requiring surgical evaluation have many different
      causes. CASE: In an unusual case, a pelvic mass was found to comprise
      approximately 40 gallstones. Laparoscopy was performed, and the gallstones were
      removed easily. CONCLUSION: Nongynecologic causes should be considered in the
      differential diagnosis of pelvic masses.

PMID- 9572185
TI  - Remarkable response of primary squamous cell carcinoma of the ovary to paclitaxel
      and cisplatin.
AB  - BACKGROUND: The survival rate of patients with advanced stage primary squamous
      cell carcinoma of the ovary is dismal and the best treatment is unknown. We
      describe the response of this tumor to systemic chemotherapy employing paclitaxel
      and cisplatin. CASE: A 31-year-old white woman diagnosed with International
      Federation of Gynecology and Obstetrics stage IV primary squamous cell carcinoma
      of the ovary associated with ovarian endometriosis underwent cytoreductive
      surgery followed by paclitaxel and cisplatin every 4 weeks for 12 courses. The
      patient tolerated chemotherapy well, demonstrated a dramatic response with
      disappearance of hepatic metastases, and remains without evidence of disease 2
      years after diagnosis. CONCLUSION: Paclitaxel and cisplatin may be effective in
      treating primary squamous cell carcinoma of the ovary.

PMID- 9572186
TI  - Uterine and ovarian conservation in advanced small cell carcinoma of the ovary.
AB  - BACKGROUND: The decision to recommend removal or conservation of a normal ovary
      and uterus in a young woman with advanced ovarian cancer is difficult and
      controversial. CASE: A 21-year-old patient with a large-cell variant of small
      cell carcinoma of the ovary stage IIIc underwent optimal debulking surgery with
      preservation of the normal appearing uterus and opposite adnexa followed by
      aggressive multi-agent chemotherapy. She is menstruating normally and is free of
      disease, more than 2 years since completion of chemotherapy. CONCLUSION: In
      selected cases, conservation of the uninvolved ovary and uterus in patients with
      advanced-stage, small-cell carcinoma of the ovary may not compromise survival.

PMID- 9572187
TI  - Rapid progression to invasive cervix cancer in a woman infected with the human
      immunodeficiency virus.
AB  - BACKGROUND: Previous studies have shown an increased risk of cervical dysplasia
      in women infected with human immunodeficiency virus (HIV), as well as an
      increased risk of progression to higher-grade lesions. It is not known whether
      the rate of progression is accelerated over that in immunocompetent women. CASE:
      During September 1991, an HIV-positive woman underwent conization of the cervix
      showing carcinoma in situ. The surgical margins and endocervical curettings were
      negative for dysplasia. Papanicolaou smears 4 and 7 months after the conization
      also were negative. She then presented 33 months postconization with a stage Ib2
      cervical carcinoma, which proved resistant to chemotherapy and pelvic radiation.
      CONCLUSION: Immunosuppression caused by HIV infection may cause a more rapid
      progression of cervical intraepithelial lesions to carcinoma.

PMID- 9572188
TI  - Ovulation induction and normal pregnancy after panhypopituitarism due to
      lymphocytic hypophysitis.
AB  - BACKGROUND: Lymphocytic hypophysitis is an unusual autoimmune disease that causes
      partial or total hypopituitarism and often is associated with pregnancy. Only
      four spontaneous pregnancies have been reported after this disease. We report a
      case of ovulation induction in a woman with this antecedent as well as the course
      of the subsequent pregnancy. CASE: Ovulation was induced with gonadotropins in a
      31-year-old woman with panhypopituitarism secondary to lymphocytic hypophysitis,
      achieving an uncomplicated single intrauterine pregnancy. A term healthy infant
      was delivered by cesarean. Clinical course during puerperium was normal.
      CONCLUSION: Ovulation induction response was similar to that in
      panhypopituitarism of any other cause. Lymphocytic hypophysitis antecedent did
      not adversely affect pregnancy outcome nor was pregnancy-related disease relapse
      observed.

PMID- 9572189
TI  - Stress urinary incontinence due to prescription medications: alpha-blockers and
      angiotensin converting enzyme inhibitors.
AB  - BACKGROUND: Several antihypertensive medications affect lower urinary tract
      function and may cause urinary incontinence. CASE: A 59-year-old woman on
      doxazosin mesylate for control of her hypertension presented with stress urinary
      incontinence. Because this drug is known to cause loss of urethral tone leading
      to stress incontinence in some patients, she was switched to enalapril maleate,
      an angiotensin converting enzyme inhibitor. Her incontinence improved on the new
      medication, but she developed a persistent dry cough that continued to cause
      episodic stress incontinence. Because a persistent cough is a known side effect
      of angiotensin converting enzyme inhibitors, her medication was changed to a
      calcium channel blocker, amlodipine besylate. Her cough resolved, and her stress
      incontinence was no longer a clinical problem. CONCLUSION: Gynecologists should
      be aware of the unexpected side effects of medications on the lower urinary
      tract.

PMID- 9572190
TI  - Transabdominal cerclage: a laparoscopic approach.
AB  - BACKGROUND: The placement of a transabdominal cervical cerclage has been regarded
      as considerably more morbid than a transvaginal cerclage, in part due to the need
      for two laparotomies. We describe a technique for the laparoscopic placement and
      removal of a transabdominal cerclage. CASES: Two cases of women with insufficient
      cervical tissue to place a transvaginal cerclage were managed with a
      transabdominal cerclage. In one case, the cerclage was placed laparoscopically;
      in the other, the band was removed, facilitating uterine evacuation following the
      diagnosis of a missed abortion. In both cases a laparotomy was avoided.
      CONCLUSION: Laparoscopic placement and removal of a transabdominal cerclage are
      promising options in the treatment of an incompetent cervix.

PMID- 9572191
TI  - Ureteral endometriosis diagnosed at ureteroscopy.
AB  - BACKGROUND: Intrinsic ureteral endometriosis is rare. Early detection and
      treatment is extremely important to preserve renal function. CASE: A 37-year-old
      woman with right flank pain was diagnosed with a polypoid lesion at excretory
      urogram. The polyp was removed under ureteroscopy and was found to be
      endometriosis. Subsequent exploratory laparotomy and ureterolysis failed to
      document other foci of endometriosis. Resection of the ureter was not needed. She
      received medroxyprogesterone for 6 months, and a ureteral stent was left in place
      for 3 months postoperatively. Excretory urogram showed no obstruction 6 months
      postoperatively. CONCLUSION: This appears to be the first reported case of
      ureteral endometriosis documented initially at ureteroscopy. Prompt treatment may
      relieve symptoms and preserve renal function. Resection of the ureter may be
      avoided in some patients.

PMID- 9572192
TI  - Rocky Mountain spotted fever in pregnancy.

PMID- 9572193
TI  - Midtrimester diagnosis of a diffuse cutaneous cavernous lymphangioma.

PMID- 9572194
TI  - Prenatal sonographic diagnosis of Treacher Collins syndrome.

PMID- 9572195
TI  - Placental pathology in maternal and neonatal myeloproliferative disorders.

PMID- 9572196
TI  - Aortic dissection and myocardial infarction in a pregnant patient with Turner
      syndrome.

PMID- 9572197
TI  - Pregnancy and delivery complicated by mitochondrial myopathy, encephalopathy,
      lactic acidosis, and stroke-like episodes.

PMID- 9572198
TI  - Spontaneous monozygotic quadruplet pregnancy: an obstetric rarity.

PMID- 9572199
TI  - Advanced cervical cancer complicated by previous LeFort operation.

PMID- 9572200
TI  - Peritoneal tuberculosis versus advanced ovarian cancer: a diagnostic dilemma.

PMID- 9572201
TI  - Rudimentary uterine horn pregnancy diagnosed with magnetic resonance imaging.

PMID- 9572202
TI  - Laparoscopic management of a laparoscopic complication.

PMID- 9572203
TI  - Iliohypogastric nerve entrapment following gynecologic operative laparoscopy.

PMID- 9572204
TI  - Management of diabetes by obstetrician-gynecologists.
AB  - OBJECTIVE: To examine the rates of diagnosis and treatment of diabetes mellitus
      by ACOG Fellows in pregnant and nonpregnant patients. METHODS: We sent a
      questionnaire to 1250 ACOG Fellows. Thirty-nine percent responded. Responses were
      examined for potential differences between recently and less recently trained
      obstetrician-gynecologists. RESULTS: Ninety-six percent of obstetricians
      routinely screen for gestational diabetes mellitus (GDM). Fifty-five percent of
      obstetrician-gynecologists screen for diabetes in nonpregnant patients if there
      is a history of diabetes in the patient's family. Moreover, 33% care for women
      with type-1 diabetes mellitus, and 39% for women with type-2 diabetes mellitus
      who are not pregnant. Sixty-two percent believed that their patients with GDM are
      at increased risk for developing nongestational diabetes later in life, and 71%
      will recommend an evaluation of glucose tolerance in the future for these women.
      Finally, 99% are willing to prescribe oral contraceptives to women diagnosed
      previously with GDM. CONCLUSION: Obstetrician-gynecologists are aware of the need
      to screen for GDM and the importance of postpartum follow-up in GDM patients to
      detect type-2 diabetes mellitus. This practice is important because half of the
      14 million people with type-2 diabetes mellitus are unaware they have this
      disorder, and many learn about it only after a serious complication has occurred.

PMID- 9572205
TI  - Prenatal genetic testing: content of discussions between obstetric providers and
      pregnant women.
AB  - OBJECTIVE: To document the content and accuracy of discussions about prenatal
      genetic testing between obstetric providers and pregnant women. METHODS: The
      first prenatal visits of 169 pregnant women with 21 obstetricians and 19
      certified nurse-midwives were audiotaped and analyzed for whether a discussion of
      family history or genetic testing took place and if so, its length, content, and
      accuracy. RESULTS: Family history was discussed in 60% of visits, maternal serum
      marker screening in 60%, second-trimester ultrasonography for fetal anomalies in
      34%, and for women at least 35 years old, amniocentesis or chorionic villus
      sampling (CVS) in 98%. The length of discussions of genetic testing averaged 2.5
      minutes for women younger than 35 years of age and 6.9 minutes for older women.
      Topics discussed most often were the practical details of testing, the purpose of
      testing, and the fact that testing is voluntary. Discussions seldom were
      comprehensive. Obstetricians were more likely to make a recommendation about
      testing than were nurse-midwives and were less likely to indicate that testing is
      voluntary. Most women were satisfied with the amount of information, and the
      majority of women of advanced maternal age had made a decision about
      amniocentesis or CVS by the end of the visit. CONCLUSION: The information about
      genetic testing provided in the first prenatal visit is inadequate for ensuring
      informed autonomous decision-making. Guidelines addressing the content of these
      discussions should be developed with input from obstetricians, nurse-midwives,
      genetic counselors, and pregnant women.

PMID- 9572206
TI  - A randomized trial of nurse intervention to reduce preterm and low birth weight
      births.
AB  - OBJECTIVE: To test the effect of telephone calls from registered nurses to low
      income pregnant women on the rates of low birth weight (LBW) and preterm births.
      METHODS: A total of 1554 women receiving prenatal care in a public clinic who met
      study criteria and who consented were assigned randomly to intervention and
      control groups. Women in the intervention group received telephone calls from a
      registered nurse, one or two times weekly from 24 weeks' through 37 weeks'
      gestation. Relative risks (RRs) and 95% confidence intervals (CIs) were
      calculated. RESULTS: Low birth weight rates were 10.9% in the intervention group
      and 14.0% in the control group (RR 0.75; 95% CI 0.55, 1.03; P = .072). For
      gestational age less than 37 weeks, rates were 9.7 in the intervention group and
      11.0 in the control group (RR .87; 95% CI 0.62, 1.22; P = .415). In the subgroup
      of low-income black women 19 years of age and older, a statistically significant
      difference was found in preterm birth rates before 37 weeks (8.7% in the
      intervention group versus 15.4% in the controls [RR 0.56; 95% CI 0.38, 0.84; P =
      .004]). CONCLUSION: There was no difference in LBW or preterm births between
      intervention and control groups in the total sample. In a secondary analysis of
      black subjects 19 years of age and older, there was a significant difference in
      preterm birth rates.

PMID- 9572207
TI  - The long-term consequences of thrombotic microangiopathy (thrombotic
      thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy.
AB  - OBJECTIVE: To characterize perinatal outcomes and long-term maternal
      complications from thrombotic microangiopathy manifested during pregnancy, and to
      review the clinical course and long-term follow-up of pregnant women with this
      condition at our institution over the past 25 years. METHODS: We identified
      prospectively pregnant women who met clinical and laboratory criteria for
      thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Their clinical
      and laboratory findings, response to treatment, perinatal outcomes, and long-term
      sequelae were then analyzed. RESULTS: Between 1972 and 1997, 11 women had 13
      pregnancies complicated by thrombotic microangiopathy, representing an incidence
      of one per 25,000 births. In three pregnancies (23%), severe and refractory
      disease developed before midpregnancy. In ten other pregnancies, disease
      developed either peripartum (62%) or several weeks postpartum (15%). In only two
      pregnancies with peripartum or postpartum onset of disease was there a clinical
      picture of severe preeclampsia. In general, the response to treatment was prompt.
      One woman died of her initial disease in early pregnancy, and mean follow-up of
      nine survivors was 8.7 years. Disease recurred at least once in 50% of these, two
      during a subsequent pregnancy. There was at least one serious long-term sequela
      in all but two survivors; these included recurrence of thrombotic
      microangiopathy, renal failure, severe hypertension, chronic blood-borne
      infections, and death. CONCLUSION: Thrombotic microangiopathy complicating
      pregnancy is rare, and with careful evaluation, it should not be confused with
      atypical preeclampsia. With prompt and aggressive treatment including plasma
      exchange, the likelihood of immediate survival is high; however, long-term
      morbidity and mortality are common.

PMID- 9572208
TI  - Disturbed feto-maternal cell traffic in preeclampsia.
AB  - OBJECTIVE: To investigate whether the transfer of fetal blood cells to the
      maternal circulation is perturbed in pregnancies affected by preeclampsia.
      METHODS: Fetal erythroblasts were isolated from eight women with clinically
      diagnosed preeclampsia (blood pressure values of at least 140/90 mmHg and
      associated proteinuria) and an equal number of matched corresponding controls.
      All patients in both groups were pregnant with male singleton fetuses. The
      presence of fetal cells was evaluated histologically and by fluorescence in situ
      hybridization for X and Y chromosomes. RESULTS: The number of fetal cells was
      higher in preeclamptic patients than in controls, with respect to both nucleated
      red blood cells (median per 200 cells 38 versus 7; P < .001) and the proportion
      of these cells that were of fetal origin (median per 2000 cells 9 versus 2; P =
      .001). CONCLUSION: These results suggest that the trafficking of fetal cells into
      the maternal periphery is disturbed in patients with preeclampsia. Because it is
      unlikely that such an altered flow of cells is restricted to the erythroblasts
      examined in this study, these findings also may lead to interesting new concepts
      regarding the development of preeclampsia and possibly the associated syndrome of
      hemolysis, elevated liver enzymes, and low platelets.

PMID- 9572209
TI  - Timing of estrogen replacement therapy following hysterectomy with oophorectomy
      for endometriosis.
AB  - OBJECTIVE: To determine whether the immediate initiation of estrogen replacement
      therapy (ERT) in the postoperative period increases the incidence of symptom
      recurrence following total abdominal hysterectomy (TAH) with bilateral salpingo
      oophorectomy (BSO) for the treatment of endometriosis. METHODS: In a
      retrospective cohort study, 95 women who underwent TAH with BSO for endometriosis
      at the Johns Hopkins Hospital during 1979-1991 and who subsequently received ERT
      were identified by computer search. Follow-up information was obtained from
      medical records, outpatient charts, and telephone surveys. Pain recurrence in
      patients who started ERT within 6 weeks after surgery and in those who delayed
      ERT for more than 6 weeks was compared and adjusted for length of patient follow
      up and other covariates. RESULTS: Sixty women began ERT within the immediate
      postoperative period, and four (7%) of them had recurrent pain; 35 women began
      ERT more than 6 weeks after surgery, and seven (20%) of them had recurrent pain.
      The mean length of follow-up was 57 months. The difference in the crude rate of
      symptom recurrence following early and delayed initiation of ERT after TAH with
      BSO was not statistically significant (P = .09). Controlling for length of
      patient follow-up, no significant differences were observed between the two
      groups. Adjusting for covariates of stage, age, and postoperative adjunct
      medroxyprogesterone therapy, those who started ERT more than 6 weeks after
      surgery had a relative risk of 5.7 (95% confidence interval 1.3, 25.2) for pain
      recurrence. CONCLUSION: Although the number of patients in the study was too
      small to reach statistical significance in all analyses, these findings suggest
      that patients who begin ERT immediately after TAH with BSO are at no greater risk
      of recurrent pain than those who delay ERT for more than 6 weeks.

PMID- 9572210
TI  - Bleeding pattern and endometrial changes during continuous combined hormone
      replacement therapy. The Ogen/Provera Study Group.
AB  - OBJECTIVE: To establish the optimum oral daily dose of micronized
      medroxyprogesterone acetate, given in combination with a fixed oral dose of
      estrone (E1) sulfate as hormone replacement therapy, that provides endometrial
      protection and induces cessation of vaginal bleeding. METHODS: This multicenter,
      randomized, double-blind study was conducted for 2 years. Five hundred sixty
      eight postmenopausal women were randomized to take E1 sulfate 1.25 mg daily and
      one of three doses of medroxyprogesterone acetate (2.5, 5, or 10 mg) daily. Any
      vaginal bleeding was recorded by patients in a daily diary, and endometrial
      biopsies were performed at entry into the study and at 3, 12, and 24 months.
      RESULTS: Forty-two percent of all women reported some bleeding at month 3 of
      therapy. However, by month 6, 76.5, 80.1, and 80.9% of women were amenorrheic in
      the 2.5-, 5-, and 10-mg medroxyprogesterone acetate groups, respectively. Over
      time, the percentage of women with no bleeding increased in each group, and by 24
      months 91.5, 89.9, and 94.3% were amenorrheic in the 2.5- and 10-mg
      medroxyprogesterone acetate groups, respectively. Approximately 10% of women
      continue to have some bleeding, regardless of the dose of medroxyprogesterone
      acetate. There were no statistically significant differences in the number of
      women with bleeding at any time point between the three groups. There were no
      cases of endometrial hyperplasia reported in the study population over the 2
      years. CONCLUSION: All three studied doses of medroxyprogesterone acetate, given
      in combination with 1.25 mg of E1 sulfate, provide adequate endometrial
      protection and render approximately 80% of women amenorrheic by 6 months of
      therapy.

PMID- 9572211
TI  - Immunohistochemical localization of activin A in human endometrial tissues during
      the menstrual cycle and in early pregnancy.
AB  - OBJECTIVE: To investigate the possible localization of activin A in human
      endometrial tissue. METHODS: Human endometrial tissue was collected from 33
      patients who were undergoing abdominal hysterectomy. Human decidual tissue was
      collected from 11 patients, who were having a therapeutic abortion. Tissue was
      fixed in Bouin's solution and made into paraffin sections. Tissue sections were
      stained with monoclonal antibodies against the inhibin/activin alpha- and betaA
      subunits and activin A using an avidin-biotin-peroxidase complex technique.
      RESULTS: No immunostaining with antibody against the alpha-subunit was observed
      in the human endometrium during the menstrual cycle or in the decidua during
      early pregnancy. By contrast, immunostaining for the betaA-subunit and activin A
      was observed in the cytoplasm of endometrial glands at all phases of the
      menstrual cycle and in the decidua during early pregnancy. The intensity of
      immunostaining for the betaA-subunit was strong during the menstrual phase,
      became weaker during the early proliferative phase, and was intense again at the
      late proliferative phase. The immunostaining for the betaA-subunit was weak
      during the early secretory phase and became very intense toward the midsecretory
      and late secretory phases. The intensity of immunostaining for activin A changed
      during the menstrual cycle and showed a tendency similar to that for betaA
      subunit. The stromal cells were weakly immunoreactive with antibodies against the
      betaA-subunit and activin A from the menstrual to the midsecretory phase and
      became strong in the late secretory phase. Intense staining for the betaA-subunit
      and activin A was observed in the cytoplasm of decidual cells during early
      pregnancy. CONCLUSION: Activin A, but not inhibins, is localized in the
      endometrial tissue. The endometrium may be a major source of activin A during the
      normal menstrual cycle, and the decidua may be one of the sources of activin A
      during early pregnancy.

PMID- 9572212
TI  - Pattern of development of hyperprolactinemia after initiation of haloperidol
      therapy.
AB  - OBJECTIVE: To determine the time it takes for prolactin (PRL) levels to increase
      after initiation of therapy with haloperidol (a neuroleptic medication) and the
      pattern and extent of the increase. METHODS: Seventeen individuals scheduled to
      be given treatment with neuroleptic drugs were enrolled. Baseline blood specimens
      were collected for PRL and TSH levels. Follow-up samples for PRL determinations
      were obtained every 3 days for 18 days after initiation of haloperidol therapy.
      RESULTS: There were 17 subjects: 14 women and three men. Two of the subjects were
      found to have hyperprolactinemia due to hypothyroidism and were excluded from the
      basic study. The 15 remaining subjects all had normal baseline PRL levels and
      normal TSH values. The PRL levels in all 15 showed a similar pattern: a rapid
      increase in PRL levels in the first 6-9 days, followed by a plateau that
      remained, with minor fluctuations, throughout the study. The highest mean peak
      level of PRL was 37.4 ng/mL and the maximum was 77 ng/mL. The two individuals
      with hypothyroidism had somewhat elevated baseline PRL levels; although they
      showed the same initial pattern of increase after haloperidol administration,
      their PRL levels reached values well above 100 ng/mL. CONCLUSION: There is a
      distinct pattern of response of PRL to haloperidol. The PRL level increases for 6
      9 days, then plateaus, the peak being between 30 and 50 ng/mL, and always remains
      below 77 ng/mL. In our study, levels that continued to increase, or increased
      above 77 ng/mL, indicated the presence of hypothyroidism. The patterns and levels
      of the increase were uninfluenced by the therapeutic dose of the medication
      given. Given that the patients in our study with elevated levels of TSH had such
      high levels of PRL, all patients should have TSH determinations at the initiation
      of therapy with neuroleptic medications such as haloperidol.

PMID- 9572213
TI  - Predicting probabilities of pregnancy and multiple gestation from in vitro
      fertilization--a new model.
AB  - OBJECTIVE: To develop a statistical model that adjusts for variation between
      patients and adequately predicts the observed distribution of pregnancies among
      singletons and multiple gestations of various orders. METHODS: All in vitro
      fertilization (IVF) cycles from the inception of the IVF program at Women and
      Infants' Hospital on May 26, 1988, until December 31, 1993, were evaluated using
      logistic regression in selected subsets. RESULTS: A new cycle-one specific model
      uses three different probabilities: P1, the probability of pregnancy (predicted
      by age and total embryo score); P2/P1, the conditional probability of finding a
      second implantation in those who had become pregnant with at least one (predicted
      by total embryo score); and P3/P2, the conditional probability of finding a third
      implantation in those who had become pregnant with at least two (with no
      significant predictors). This is the first model to use these three adjusted
      probabilities. CONCLUSION: P1 increases with increasing total embryo score but
      decreases with increasing age. P2/P1 increases with increasing total embryo score
      but does not depend on age. Embryo scoring is useful because the total embryo
      score is a better predictor of P1 and P2/P1 than the number of embryos alone. By
      using patient-specific information (age and total embryo score) and cycle
      specific tables, an estimate of the probability of pregnancy and multiple
      gestation can be provided before embryo transfer.

PMID- 9572214
TI  - Long-term outcome of laparoscopic presacral neurectomy for the treatment of
      central pelvic pain attributed to endometriosis.
AB  - OBJECTIVE: To evaluate the long-term pain reduction achieved by laparoscopic
      presacral neurectomy. METHODS: One hundred seventy-six women with median (range)
      age 30 (18-45) years underwent presacral neurectomy combined with excision and
      vaporization of endometriotic lesions and were observed, using structured
      questionnaires, for up to 72 months postoperatively. The study included a
      convenience sample of the first 100 questionnaires returned. Forty of the women
      were studied for 12-23 months, and 60 for 24-72 months. The main outcome measures
      were reduction of pelvic pain, dysmenorrhea, and dyspareunia after surgery.
      RESULTS: Pelvic pain, dysmenorrhea, and dyspareunia were reportedly reduced by
      more than 50% in 74, 61, and 55 patients, respectively, more than 12 months after
      laparoscopic presacral neurectomy. More than 50% reduction in pelvic pain was
      reported by 69.8%, 77.3%, 71.4%, and 84.6% of the patients, respectively, with
      endometriosis stages I-IV, using the revised classification of the American
      Fertility Society. Comparatively, more than 50% reduction in dysmenorrhea was
      reported by 52.8% of the patients with stage I endometriosis, 68.2% with stage
      II, 71.4% with stage III, and 69.2% with stage IV. Reduction of dyspareunia by
      more than 50% was reported by 54.7% of the patients with stage I endometriosis,
      50.0% with stage II, 28.6% with stage III, and 61.5% with stage IV. CONCLUSION:
      Long-term outcome of laparoscopic presacral neurectomy is satisfactory in the
      majority of patients. The stage of endometriosis is not related directly to the
      degree of pain improvement achieved.

PMID- 9572215
TI  - Quantification of cough-related urine loss using the paper towel test.
AB  - OBJECTIVE: To develop and test a simple and rapid method for quantifying the
      urine loss resulting from three deep coughs using an ordinary brown paper towel.
      METHODS: A brown paper towel is held lightly against the perineum during three
      single coughs performed in the upright stance. The resulting wetted area was
      calculated using simple geometry; if desired, leakage volume can be interpolated
      from a calibration curve, which demonstrates the relationship between wetted area
      (cm2) and volume (mL) of leakage. Four bench tests of the method were performed.
      In addition, the test-retest reliability of the method was evaluated in eight
      elderly women with mild stress urinary incontinence, a sample size adequate to
      detect a 1-mL difference with 80% power. RESULTS: The smallest measurable
      quantity of fluid resulted in a wetted area of 0.04 cm2 (equivalent to 0.2
      microl). For leakage volumes up to 6 mL, the regression showed that each 1 mL of
      fluid volume resulted in an average 25.4 cm2 increase in wetted area (coefficient
      of determination: 0.97). In eight women with stress incontinence 95% of within-
      and across-visit comparisons of urine loss were within 1 mL. CONCLUSION: The
      paper towel test is a simple and reliable measure providing immediate visual and
      quantitative feedback of cough-related urine loss typical of mild-to-moderate
      stress urinary incontinence.

PMID- 9572216
TI  - The effect of posterior wall support defects on urodynamic indices in stress
      urinary incontinence.
AB  - OBJECTIVE: To determine if posterior vaginal wall defects affect urodynamic
      indices and mask stress urinary incontinence. METHODS: Ninety women with grade 0,
      1, 2, or 3 posterior wall defects were evaluated prospectively by complete
      urodynamics to assess their urinary complaints. None had severe anterior or
      apical support defects. Urethral pressure profilometry and cough stress test were
      performed with the posterior wall in the unretracted position and then with the
      posterior wall retracted using a split speculum. Analysis of covariance was used
      to compare adjusted mean differences in maximum urethral closure pressure,
      functional urethral length, and units of leakage volume during the cough stress
      test in the unretracted and retracted positions among the posterior wall grade
      groups. RESULTS: In women with grade 3 posterior wall defects, there were
      significant changes from the unretracted to the retracted position in maximum
      urethral closure pressure of -7.0 cm H20, (99% confidence interval [CI] -12.4, 
      1.6), functional urethral length of -0.3 cm (99% CI -0.5, -0.1), and leak volume
      units of +0.7 (99% CI 0.4, 1.0) during the cough stress test. There were four
      women with grade 3 posterior wall defects who demonstrated potential stress
      incontinence when their posterior wall was retracted. CONCLUSION: A grade 3
      posterior wall defect may artificially raise maximum urethral closure pressure,
      increase functional urethral length, and mask urinary stress incontinence during
      a cough stress test. Women with grade 3 posterior wall defects should be tested
      with the posterior wall retracted during urodynamic evaluation.

PMID- 9572217
TI  - An anatomic approach to pelvic hemorrhage during sacrospinous ligament fixation
      of the vaginal vault.
AB  - OBJECTIVE: To examine the current clinical problem of life-threatening hemorrhage
      during sacrospinous vaginal vault suspension, define a management solution, and
      validate current anatomic knowledge of the area involved. METHODS: Ten cadaveric
      female pelves were dissected from a posterior gluteal approach and from an
      abdominal approach. The vascularity of the region of the sacrospinous ligament
      was mapped. RESULTS: There are multiple and varied collateral vascular supplies
      and anastomoses in the region of the sacrospinous ligament and buttock,
      including: 1) superior gluteal, 2) inferior gluteal, 3) internal pudendal, 4)
      vertebral, 5) middle sacral, 6) lateral sacral, and 7) external iliac via the
      circumflex femoral artery system. Anastomoses occurred in all pelves examined.
      The frequency of each type of anastomosis varied from 20-100%. CONCLUSION:
      Surgical ligation of the internal iliac artery would not likely curb massive
      hemorrhage during sacrospinous ligament fixation, except in certain cases of
      internal pudendal vascular injury. The inferior gluteal artery is probably the
      most commonly injured vessel in sacrospinous ligament suspension because of its
      location. Inferior gluteal vessel injury should be approached by the use of
      packing and vascular clips or packing and arterial embolization. These latter
      approaches should be of primary consideration in the control of hemorrhage at the
      time of sacrospinous ligament fixation.

PMID- 9572218
TI  - Promoting smoking cessation among women who seek cervical cancer screening.
AB  - OBJECTIVE: To determine whether 1) women smokers are aware that smoking increases
      their risk for cervical cancer; 2) awareness of risk factors and its impact on
      motivation to quit smoking vary by age; and 3) providers are advising smokers to
      quit smoking during routine gynecologic visits. METHODS: Women aged 18 years and
      older who had a Papanicolaou test in the prior month were identified from a
      managed care cytology database. Four weeks after receiving their test result,
      women were called to complete a health behavior survey in which their smoking
      status, sexual history, knowledge of risk factors for cervical cancer, and
      motivation to quit smoking were assessed. RESULTS: Only 49% of the 613 smokers
      surveyed were aware that smoking increased their risk of cervical cancer. Women
      aged 34 years and younger were significantly more likely to agree that smoking
      increased their risk for cervical cancer than women aged 45 years or older (54%
      versus 40%). Concern that smoking might cause cervical cancer or other cancers
      was endorsed highly by women as a motivator for cessation, particularly for women
      smokers aged 18-26 (mean 8.1 and 7.6 on 10-point scales, respectively). About 50%
      of the women reported that their provider had asked about smoking and had
      encouraged cessation. Only about 30% of smokers were aware of well-established
      risk factors for cervical cancer such as the number of lifetime sexual partners
      and not using a condom. CONCLUSION: Routine gynecologic screening visits
      represent an important and underutilized clinical opportunity to intervene with
      young women smokers.

PMID- 9572219
TI  - Clinical chorioamnionitis and the prognosis for very low birth weight infants.
AB  - OBJECTIVE: To determine the effects of clinical chorioamnionitis on neonatal
      morbidity and mortality in very low birth weight infants. METHODS: This was an
      observational cohort analysis of all singleton live-born infants weighing 500
      1500 g at 24 weeks' or greater gestational age and born between 1988 and 1996 at
      Parkland Memorial Hospital, Dallas, Texas. Chorioamnionitis was diagnosed on the
      basis of maternal fever of 38C with supporting clinical evidence, which included
      fetal tachycardia, uterine tenderness, and/or malodorous infant, and the absence
      of another source of infection. Multiple logistic regression analysis was used to
      adjust for outcomes of interest. RESULTS: Ninety-five of 1367 very low birth
      weight infants (7%) were exposed to chorioamnionitis. Neonatal sepsis,
      respiratory distress syndrome, seizure in the first 24 hours of life,
      intraventricular hemorrhage (grade 3 or 4), and periventricular leukomalacia were
      all significantly increased with chorioamnionitis, after adjusting for preterm
      ruptured membranes, pregnancy-associated hypertension, cesarean birth,
      gestational age, and birth weight. The odds ratios for intraventricular
      hemorrhage, periventricular leukomalacia, and seizures in the first 24 hours were
      2.8 (95% confidence interval [CI] 1.6, 4.8), 3.4 (95% CI 1.6, 7.3), and 2.9 (95%
      CI 1.2, 6.8), respectively. CONCLUSION: Our results suggest a link between
      clinical chorioamnionitis and several indices of neonatal morbidity in the very
      low birth weight infant. Chorioamnionitis appears to make the very low birth
      weight infant particularly vulnerable to neurologic damage.

PMID- 9572220
TI  - Pathology slide review in gynecologic oncology.
AB  - OBJECTIVE: To analyze the diagnostic accuracy and alteration in treatment
      planning from interinstitution (different institution) pathologic consultation.
      METHODS: We reviewed pathologic reports from 720 referred patients. The diagnosis
      rendered from a gynecologic pathologist was compared with the original diagnosis.
      Discrepancies were coded as none, minor, or major. A discrepancy was major if it
      led to treatment alteration. A discrepancy was minor if it did not lead to
      treatment alteration. The judgment to declare a discrepancy was made by a
      gynecologic pathologist, a gynecologist, and three gynecologic oncologists. The
      review cost was $150 per case. The Cochran-Mantel-Haenszel test evaluated any
      systematic pattern in discrepancies. RESULTS: Seven hundred twenty specimens
      consisted of 113 vulvar, 170 uterine, 289 cervical, 105 ovarian, and 43 vaginal
      tissues. Six hundred one (84%) pathologic diagnoses showed no discrepancy. There
      were 104 (14%) minor and 15 (2%) major discrepancies. After reviewing 15 major
      discrepancies, six surgeries were canceled, two surgeries were modified, one
      adjuvant radiation treatment was added, one chemotherapy treatment was modified,
      and five adjuvant chemotherapy treatments were cancelled. No systematic error was
      identified with regard to the sources (tissue origin) or methods of obtaining the
      specimen (P = .675). The cost of reviewing 720 specimens was $108,000. The cost
      of identifying each major discrepancy was $7200. CONCLUSION: Reviewing pathology
      slides before definitive treatment reveals notable discrepancies in diagnoses.
      The cost of pathology review is globally expensive but has consequential impact
      on proper treatment planning for the individual patient.

PMID- 9572221
TI  - Nonviral vector-mediated thymidine kinase gene transfer and ganciclovir treatment
      in leiomyoma cells.
AB  - OBJECTIVE: To test the hypotheses that ganciclovir is cytotoxic to leiomyoma
      cells transfected with herpes simplex virus thymidine kinase and that estrogen
      modulates the responsiveness of tumor cells to this gene therapy approach.
      METHODS: Human and rat cultured uterine leiomyoma cells were transfected with
      plasmids encoding the beta-galactosidase gene, thymidine kinase gene, or a
      control plasmid. Transfection efficiency was monitored by measuring beta
      galactosidase enzyme activity. Ganciclovir cytotoxicity in thymidine kinase
      transfected cells was assessed by monitoring cell viability using trypan blue
      exclusion. The "bystander effect," a phenomenon in which thymidine kinase
      expressing cells exposed to ganciclovir are toxic to adjacent thymidine kinase
      nonexpressing cells, was assessed when thymidine kinase vector-transfected cells
      were cocultured with control plasmid-transfected cells at various percentages
      before exposure to ganciclovir. The effect of estradiol on ganciclovir-thymidine
      kinase-mediated cytotoxicity was assessed in estrogen-responsive rat leiomyoma
      cells. RESULTS: A thymidine kinase-ganciclovir-mediated "bystander effect" was
      demonstrated, with 48.6% (human) and 65.6% (rat) cell death when 5% of the
      leiomyoma cells were transfected with the pNGVL1-tk vector, with 0.84% and 1.9%
      of the cells expected to express thymidine kinase as based on the 16.7% and 39.8%
      transfection efficiency determined by the reporter gene assay in human and rat
      leiomyoma cells, respectively. Estradiol promoted cell growth and enhanced the
      "bystander effect" in rat leiomyoma cells. CONCLUSION: These findings demonstrate
      the feasibility of using thymidine kinase gene therapy as a novel treatment for
      uterine leiomyomas. The effect of estrogen may provide a mechanism to enhance the
      tumor-suppressive effect of this approach.

PMID- 9572222
TI  - Meconium: a marker for peripartum infection.
AB  - OBJECTIVE: To test the hypothesis that the presence of meconium-stained amniotic
      fluid (AF) is associated with maternal and neonatal infection, both before and
      after delivery. METHODS: Nine hundred thirty-six laboring women were analyzed for
      the presence of meconium in amniotic fluid and occurrence of peripartum
      infection. Meconium was assessed clinically as thin, moderate, or thick. Intra
      amniotic infection and endometritis were diagnosed by standard definitions. All
      patients were tested for vaginal group B streptococcus, bacterial vaginosis, and
      other aerobic organisms. RESULTS: Meconium-stained AF was present in 28% of the
      study participants (9% thin, 12% moderate, 7% thick). The presence of meconium
      was associated with increased intra-amniotic fluid (17% versus 9%, relative risk
      [RRI 1.98, 95% confidence interval [CI] 1.3, 3.1), endometritis (10% versus 5%,
      RR 2.38, 95% CI 1.3, 4.4), and total infection (25% versus 13%, RR 2.19, 95% CI
      1.5, 3.2). Thick meconium had higher infection rates than clear AF (44% versus
      13%, RR 5.18, 95% CI 2.9, 9.3). Meconium was associated independently with
      peripartum infection by multiple logistic regression (RR 1.28, 95% CI 1.1, 1.6).
      CONCLUSION: Meconium-stained AF is associated with increased peripartum
      infection, independent of other risk factors for infection. Thick meconium, in
      particular, is associated with a marked increase in peripartum infectious
      morbidity.

PMID- 9572223
TI  - Intrapartum sonography and persistent occiput posterior position: a study of 408
      deliveries.
AB  - OBJECTIVE: To use intrapartum sonography as a tool to investigate the development
      of the persistent occiput posterior position during labor, as well as to identify
      parameters correlating with the outcome of labor. METHODS: A prospective study of
      408 women in labor after 37 weeks' gestation with a singleton fetus in a vertex
      position using sonography at the onset of labor was performed. Fetal position,
      placental location, and maternal BMI (body mass index) were recorded. Outcome of
      labor was monitored for all relevant parameters. RESULTS: Most (68%) of
      persistent occiput posterior positions develop through a malrotation during labor
      from an initially occipitoanterior position. Only 32% of persistent cases were
      occipitoposterior (dorsoposterior) at the onset of labor; operative interventions
      were required in 87.5% of these. Of the 61 (15%) occipitoposterior positions at
      the onset of labor, 53 (87%) rotated into an occiput anterior position.
      Persistent occiput posterior position was more common in the initially
      occipitoposterior group (P < 0.01, Fisher exact test), and posterior placental
      locations were fewer (z test, P = 0.05). Also, operative deliveries were more
      common in the group remaining occipitoposterior throughout labor (P < .01, Fisher
      exact test). A higher maternal BMI correlated with neonatal weight (P < .01,
      Pearson correlation), an increase in operative deliveries (P = .032, Pearson
      correlation), lower Apgar scores at 1 minute (P = .02, Spearman correlation), and
      increase in posterior placental locations (P = .037, two-tailed t test).
      CONCLUSION: In most cases, persistent occiput posterior position develops through
      a malrotation and only in a little more than one-third of cases through absence
      of rotation from an initially occipitoposterior position. Higher maternal BMI
      correlates with higher fetal weight, increased operative deliveries, lower Apgar
      scores at 1 minute, and posterior placental locations. Intrapartum sonography
      proved to be useful in investigating the development of the persistent
      occipitoposterior position.

PMID- 9572224
TI  - Routine ultrasound screening in pregnancy and the children's subsequent
      neurologic development.
AB  - OBJECTIVE: To test the null hypothesis of no association between ultrasound
      exposure in early fetal life and impaired neurologic development in childhood.
      METHODS: Study of children age 8-9 years whose mothers participated in a
      randomized controlled trial of ultrasound screening during pregnancy in Sweden
      during 1985-1987. Of 4637 eligible singletons, 3265 (70%) were studied through a
      questionnaire to their mothers. Assessment of neurologic development was based on
      parents' report of their child's speech and motor development. Behavioral
      disorders were assessed by a ten-item parent scale. Analyses were performed
      according to both assignment and ultrasound exposure. With a sample size of 1600
      children in each group, a two-sided alpha of .05 and beta of .10, a risk ratio of
      less than 1.4 for the studied variables could not be detected. RESULTS: Delayed
      speech development was reported by 2.9% in the screening group compared with 2.4%
      in the nonscreening group (odds ratio [OR] 1.21; 95% confidence interval [CI]
      0.79, 1.88). Similar prevalences were found when analysis was according to
      ultrasound exposure (OR 1.19, 95% CI 0.78, 1.83). Delayed motor development was
      reported by 7.6% in the screening group compared with 7.2% in the nonscreening
      group (OR 1.05; 95% CI 0.81, 1.37). Corresponding figures for ultrasound-exposed
      and -unexposed were 7.7% and 7.2%, respectively (OR 1.08; 95% CI 0.83, 1.40).
      There also were no significant differences in behavioral disorders between
      screened and unscreened children or between exposed and unexposed children,
      respectively, according to parents' ratings. CONCLUSION: No significant
      difference in impaired neurologic development between ultrasound-exposed and 
      unexposed children was found in this study.

PMID- 9572225
TI  - Disparate blood flow patterns in parallel umbilical arteries.
AB  - OBJECTIVE: To compare resistance to blood flow between two umbilical arteries at
      the same cord site during the second half of pregnancy. METHODS: We evaluated 80
      patients with singleton pregnancies cross-sectionally at gestational ages ranging
      from 20-40 weeks' gestation. Resistance to blood flow was measured separately by
      means of systolic-diastolic ratio (S/D) for both umbilical arteries of each
      subject at the same site of transverse cord section. The higher mean value of the
      one umbilical artery was designated S/Dmax, whereas the lower mean value of the
      other paired umbilical artery was designated S/Dmin. The percent difference
      between the two values was calculated for each pair of measurements. Then these
      data were stratified by gestational age. RESULTS: The overall mean (+/- standard
      deviation [SD]) S/Dmax was significantly different from S/Dmin (2.62 +/- 0.58
      versus 2.27 +/- 0.40, respectively P < .001). The mean (+/- SD) calculated
      percent difference of 14.9 +/- 10.4% ranged in a downward trend over the course
      of late pregnancy from 29.2 +/- 17.1% in the 20-28 weeks' gestational age group
      to 10.4 +/-6.1% among those at term (37-40 weeks); the slope of this trend was 
      1.32 +/- 8.55% per week, a statistically significant trend (P < .001). There was
      a more than 20% difference in more than one quarter (29%) of the 80 pairs of
      umbilical arteries we studied. Cases with these large differences were
      concentrated mostly among those with earlier gestational ages: At term, only 8.6%
      showed this difference in flow resistance measurements. CONCLUSION: The
      resistance to blood flow in one umbilical artery often differs considerably from
      that in the other. The difference, which equalizes gradually as pregnancy
      advances, perhaps as a result of functional maturation of the Hyrtl anastomosis
      between the vessels, may have clinical importance for identification and
      evaluation of the potentially jeopardized fetuses, either as an early marker of
      fetal hypoxia or in interpretating fetal status.

PMID- 9572226
TI  - Placental nitric oxide production and umbilical artery vascular impedance in
      early pregnancy.
AB  - OBJECTIVE: To evaluate whether the vasorelaxant molecule nitric oxide (NO) and
      its second messenger cyclic guanosine monophosphate (cGMP) modulate the reduction
      in resistance within the fetoplacental circulation that occurs during the first
      trimester of pregnancy. METHODS: We studied 27 women undergoing termination of
      pregnancy for psychosocial indications between 9 and 15 weeks' gestation. Each
      had ultrasound dating of the fetus and Doppler umbilical artery (UA) flow
      investigation immediately before the operation. Placental tissue was assayed for
      nitric oxide synthase (NOS) activity and cGMP content. RESULTS: Both UA
      pulsatility index (PI) and placental endothelial NOS activity decreased
      significantly with advancing gestation (r = -.52 and -.41, respectively).
      Umbilical PI correlated positively with endothelial NOS activity and cGMP level.
      Multiple linear regression analysis indicated that cGMP contributed most strongly
      to UA PI (P < .001). CONCLUSION: Our findings suggest somewhat paradoxically that
      NOS activity and cGMP levels are highest in the early gestations, when umbilical
      PI is also high, and decrease as umbilical PI decreases. Further studies are
      required to determine whether the predominant effect of NO is that of a vascular
      relaxant or a modulator of new villous vessel formation.

PMID- 9572227
TI  - Postdelivery mortality in Tennessee, 1989-1991.
AB  - OBJECTIVE: To describe postdelivery mortality rates among residents of Tennessee
      from 1989 through 1991 and to compare these rates with those of women who had not
      delivered a live or stillborn infant in the previous year. METHODS: Postdelivery
      deaths (those occurring within a year of delivery of a live or stillborn infant)
      were identified using a computerized linkage of birth and fetal death
      certificates to death certificates of female decedents aged 15-44 years. Each
      identified postdelivery death was reviewed and categorized as either pregnancy
      related (temporally and causally related to pregnancy) or pregnancy-associated
      but-not-related (temporally but not causally related to pregnancy). Cause
      specific mortality rates were compared for women who died postdelivery with women
      who died but had not delivered in the previous year. RESULTS: We identified 129
      postdelivery deaths, one quarter of which were classified as pregnancy-related.
      The rates of postdelivery pregnancy-related and of pregnancy-associated-but-not
      related death were 14.6 and 58.7, respectively, per 100,000 women who had
      delivered. Nonwhite women were 6.9 times more likely to experience postdelivery
      pregnancy-related death and 2.0 times more likely to experience postdelivery
      pregnancy-associated-but-not-related death than were white women. The leading
      cause of death among both women who had delivered and women who had not delivered
      a live or stillborn infant in the previous year was injury, although the risk of
      death the year after delivery was lower than for women who had delivered.
      CONCLUSION: Women were less likely to die in the year after delivery than were
      women who had not delivered a live or stillborn infant in the previous year.
      However, regardless of their delivery status, injuries were the leading cause of
      death among women. Postdelivery mortality was statistically significantly higher
      in nonwhite than white women, especially for pregnancy-related deaths.

PMID- 9572228
TI  - Maternal serum dehydroepiandrosterone sulfate levels and successful labor
      induction.
AB  - OBJECTIVE: To evaluate the maternal serum dehydroepiandrosterone (DHEA) sulfate
      level as a factor associated with the outcome of labor induction. METHODS: Venous
      blood was collected from 161 women at the initiation of labor induction.
      Pregnancies complicated by maternal corticosteroid use, antepartum
      chorioamnionitis, or cesarean delivery for indications other than arrest
      disorders were excluded from analysis. In 155 women meeting inclusion criteria,
      induction followed established protocols. Serum DHEA sulfate levels were measured
      by radioimmunoassay and correlated with the outcome of each induction attempt. A
      success was defined as progression to active labor. The Welch approximate t test,
      Mann-Whitney test, Fisher exact test, simple regression, and multiple regression
      were used for statistical analysis, with P < .05 considered significant. RESULTS:
      The mean (+/- standard error) DHEA sulfate level was higher in women who
      progressed to active labor (n = 147) than in those with unsuccessful attempts (n
      = 8), (109.01 +/- 5.19 microg/dL versus 58.78 +/- 15.83 microg/dL, respectively;
      P = .02). Compared with women with DHEA sulfate levels above 70 microg/dL, women
      with lower levels had an unsuccessful induction odds ratio (OR) of 4.46 (95%
      confidence interval, 1.12, 17.67; P = .04). The OR increased as DHEA sulfate
      levels decreased. CONCLUSION: Dehydroepiandrosterone sulfate may be an important
      factor in successful labor induction.

PMID- 9572229
TI  - A randomized trial of misoprostol and extra-amniotic saline infusion for cervical
      ripening and labor induction.
AB  - OBJECTIVE: To compare the cesarean rates in women undergoing induction of labor
      with unfavorable cervices who receive either misoprostol or extra-amniotic saline
      infusion. METHODS: We assigned 250 women undergoing indicated induction of labor
      randomly to misoprostol (50 microg every 4 hours for three doses with or without
      oxytocin) or extra-amniotic saline infusion and oxytocin. Each eligible subject
      had a singleton gestation, vertex presentation, intact membranes, cervical
      dilation no more than 2 cm, and effacement no more than 50%. RESULTS: Two hundred
      forty-eight women were studied after two exclusions; 120 were assigned to
      misoprostol, and 128 to extra-amniotic saline infusion. This sample size ensured
      an 80% chance of detecting an intergroup difference in cesarean rates of at least
      two-fold. The groups were similar in age, race, parity, indication for induction,
      and gestational age. The extra-amniotic saline infusion group had a significantly
      lower median initial dilation; however, at 12 hours, this group was significantly
      more dilated. The groups also were similar in epidural use, chorioamnionitis
      rates, endometritis rates, birth weights, and neonatal outcomes. Overall, 23% of
      women underwent cesarean deliveries, 18% and 27% for the misoprostol and extra
      amniotic saline infusion groups, respectively (P = .12). There were no
      significant differences in the median time to either vaginal or cesarean delivery
      between the two groups. Eighty-one percent of women were delivered in less than
      24 hours from initiation of induction; 78% in the misoprostol group, and 84% in
      the extra-amniotic saline infusion group (P = .19). CONCLUSION: Both methods of
      labor induction appear to be equally effective in this group of women at high
      risk for cesarean delivery and prolonged induction of labor.

PMID- 9572230
TI  - A mental exercise to fight frustration.

PMID- 9572231
TI  - Chemotherapy resistance in ovarian cancer: new molecular perspectives.
AB  - OBJECTIVE: To provide the obstetrician-gynecologist with the recent advances in
      mechanisms of chemotherapy resistance in ovarian cancer. DATA SOURCES: A
      computerized search of articles published through September 1997 was performed on
      the MEDLINE Ovid and Cancerlit databases. Additional references were identified
      from the reference section of all selected papers. METHODS OF STUDY SELECTION:
      All identified references were evaluated as to their relevant contribution to our
      understanding of the basic mechanisms underlying the response to chemotherapy,
      the development of chemotherapy resistance in ovarian cancer, and possible
      strategies for therapy. TABULATION, INTEGRATION, AND RESULTS: One hundred sixteen
      references were reviewed. A brief summary of the classic concepts on resistance
      to cisplatin and paclitaxel is provided, followed by a description of the basic
      mechanisms governing apoptosis and cell cycle arrest as well as their involvement
      in cell response to chemotherapy and the development of chemoresistance. Finally,
      a brief summary of the molecular alterations described in ovarian cancer,
      together with hypothetic strategies for gene-targeted therapy, are reported.
      CONCLUSION: Cisplatin or paclitaxel chemotherapy induces arrest of the cell cycle
      or apoptosis in ovarian cancer cells. Tumor suppressor genes such as p53 play a
      paramount role in mediating this response and p21wAF1/CIP1 is a major mediator of
      p53-induced arrest of the cell cycle. Molecular alterations involving these tumor
      suppressor genes are related to the development of resistance to chemotherapy and
      represent possible targets for gene therapy in ovarian cancer.

PMID- 9572232
TI  - Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month
      study.

PMID- 9572233
TI  - What to expect from a residency program: answers from a directory of residency
      programs in obstetrics and gynecology.

PMID- 9572234
TI  - Evidence of direct connection of corticobulbar fibers to orofacial muscles in
      man: electromyographic study of individual motor unit responses.
AB  - We studied corticobulbar influence on the orbicularis oris (OR) muscles by anodal
      and magnetic transcranial stimulation and compared it to the corticospinal
      influence on first dorsal interosseous muscles of healthy human volunteers. We
      recorded single motor unit (MU) responses and applied peristimulus time histogram
      (PSTH) technique to determine their properties. Peaks in the PSTHs are assumed to
      coincide with multiple excitatory postsynaptic potentials (EPSPs) induced at the
      motoneurons by corticospinal input. We found relatively small latency variation
      of consecutive single MU responses for both muscles. Additionally, we found a
      narrow initial peak in five OR MUs after anodal stimulation. This short duration
      indicates the presence of monosynaptic cortical projection in the lower facial
      motoneurons. The EPSP amplitudes, estimated on the basis of initial peak, were
      used as a measure of the synaptic transmission efficiency. Our results support
      the concept of predominantly monosynaptic transmission at the spinal level.

PMID- 9572235
TI  - Evidence of mdx mouse skeletal muscle fragility in vivo by eccentric running
      exercise.
AB  - Duchenne muscular dystrophy is an X-linked devastating disease due to the lack of
      expression of a functional dystrophin. Unfortunately, the dystrophin-deficient
      mdx mouse model does not present clinical signs of dystrophy before the age of 18
      months, and the role of dystrophin in fiber integrity is not fully understood.
      The fragility of the skeletal muscle fibers was investigated in transgenic mice
      expressing beta-galactosidase under the control of a muscle specific promoter.
      Adult mdx/beta-galactosidase (dystrophin-negative) and normal/beta-galactosidase
      (dystrophin-positive) mice were submitted to one short session of eccentric,
      downhill running exercise. The leakage of muscle enzymes creatine kinase and beta
      galactosidase was investigated before, 1 h after, and 3 days after the running
      session. A significant and transient rise in the level of these enzymes was noted
      in the serum of mdx mice following the exercise session. Thus, the lack of
      dystrophin in the mdx model led to local microdamages to the exercised muscle
      allowing leakage of proteins from the fibers. The peak leakage was transient,
      suggesting that muscle fiber lesions were rapidly repaired following this short,
      noninvasive eccentric running session.

PMID- 9572237
TI  - Limb girdle muscular dystrophy: a pathological and immunohistochemical
      reevaluation.
AB  - Ninety-seven muscle biopsies from 81 limb girdle muscular dystrophy (LGMD)
      patients [32 autosomal recessive (AR), 15 autosomal dominant (AD), 34 sporadic]
      were morphologically reevaluated. Sarcoglycan analysis was done in 37 available
      muscle biopsies of AR and sporadic patients. Chi-square tests were used to
      analyze the relation between abnormalities in AR/sporadic versus AD cases. Eighty
      percent of the muscle biopsies showed a predominantly dystrophic pattern, 20%
      showed myopathic changes, and 17% of these also had neurogenic changes. Muscle
      histology was not significantly different between AR/sporadic and AD LGMD;
      however, the observed abnormalities were more pronounced in the AR/sporadic
      group. Collections of inflammatory cells were observed in 25% and 10% of the
      AR/sporadic and AD group, respectively. Sarcoglycanopathy was diagnosed in 25% of
      the AR and sporadic patients of the 37 families tested. We conclude that the
      histological picture of AR/sporadic and AD LGMD is essentially the same, and
      sarcoglycanopathy constitutes an important part of the AR/sporadic patients.

PMID- 9572236
TI  - Diagnostic difficulties in myasthenia gravis.
AB  - Four patients with myasthenia gravis presented with severe, largely isolated,
      bulbar and respiratory muscles weakness. Tensilon tests were positive and
      antiacetylcholine receptor (anti-AChR) antibody titers were negative in all
      patients. Only 1 patient had a greater than 10% decremental response during the
      period of respiratory failure. Although routine nerve conduction studies were
      normal, all had very low-amplitude diaphragmatic compound muscle action
      potentials. Three patients had abundant fibrillation potentials and positive
      sharp waves largely restricted to respiratory muscles. Clinical and
      electrophysiological findings improved with corticosteroids, and surprisingly,
      decremental responses became positive in all patients. The assessment of patients
      with largely isolated bulbar and respiratory muscle weakness due to myasthenia
      gravis may be difficult and misleading, as anti-AChR antibody titers may be
      negative, decremental responses may be absent, and electrophysiological
      assessment atypical. Due consideration of clinical symptomatology, a Tensilon
      test, and a trial of immunosuppression may be necessary to establish the
      diagnosis.

PMID- 9572238
TI  - Cutaneous withdrawal reflexes of the upper extremity.
AB  - We characterized reflexes of the upper limb elicited by electrical stimulation of
      the fingers. Surface electromyogram (EMG) was recorded from several upper
      extremity muscles, and a finger was stimulated through paired ring electrodes. A
      train of 4-10 shocks at a frequency of 300 Hz and an intensity 4-6 times the
      perceptual threshold was the most effective stimulus for evoking EMG activity in
      relaxed arm muscles. Habituation was prominent. Latencies of EMG activity were
      <100 ms for most proximal and forearm muscles, and at least 40 ms prior to
      voluntary withdrawal movements. The timing of EMG activity in arm muscles was
      similar to that of the E2 component of the cutaneomuscular reflex evoked in these
      same muscles during contraction, and coincided with a silent period in active
      hand muscles. We conclude that cutaneous stimuli to the fingers activate a
      complex motor pattern that tends to withdraw the hand at the same time the grasp
      is released.

PMID- 9572239
TI  - Genotypic and phenotypic changes in exhaustively grown cell lines from
      mitochondrial cytopathy patients.
AB  - Understanding the pathobiology of mitochondrial (mt) DNA diseases involves both
      characterization of the effects of individual mutations on respiratory function
      and elucidation of the changes in mutation load and distribution (energy
      mosaicism) over serial cell generations. Whether a given mutation is stably
      maintained, or increases or decreases with cell growth, is one of the
      determinants as to whether a particular tissue will be affected by oxidative
      phosphorylation failure. In this study, we correlated mt genotype with
      biochemical phenotype in myoblasts from patients with pathogenic mtDNA mutations.
      The dominant process detected was a progressive elimination of mutant mtDNA
      genomes concomitant with an improvement in respiratory chain activity, suggesting
      that energetically normal cells have a growth advantage over those with a high
      mutation load. We propose that this elimination is by biased distribution of wild
      type mtDNA to daughter cells, and that a similar mechanism could operate in vivo
      and contribute to both the clinical expression of mt disease and the maintenance
      of a predominantly wild-type mt genome pool across generations.

PMID- 9572240
TI  - Causes of neuromuscular weakness in the intensive care unit: a study of ninety
      two patients.
AB  - The spectrum of neuromuscular disorders among intensive care unit (ICU) patients
      has shifted toward disorders acquired within the ICU and away from "traditional"
      neuromuscular disorders that lead to ICU admission. We sought to assess this
      spectrum by determining the causes and relative frequencies of neuromuscular
      disorders that led to electromyography (EMG) examinations in our ICU population.
      Ninety-two patients were studied over a 4 1/2-year period. Twenty-six (28%) had
      neuromuscular disorders (mainly Guillain-Barre syndrome, myopathy, and motor
      neuron disease) that led to ICU admission. Among patients who developed weakness
      in the ICU, there was a predominance of organ transplant patients and patients
      with the systemic inflammatory response syndrome and multiorgan dysfunction.
      Thirty-nine (42%) developed acute myopathy (consistent with critical illness
      myopathy in most), and 13% developed acute axonal sensorimotor polyneuropathy
      (mainly critical illness polyneuropathy). Patients with acute myopathy and acute
      axonal sensorimotor polyneuropathy had similar functional outcomes. We conclude
      that among patients who underwent EMG in our ICU population, acute myopathy is
      three times as common as acute axonal polyneuropathy, and the outcomes from acute
      myopathy and acute axonal polyneuropathy may be similar.

PMID- 9572241
TI  - The impact of a muscle target organ on nerve grafts with different lengths--a
      histomorphological analysis.
AB  - The present study was done in order to evaluate the influence of a target muscle
      on the regenerative processes in long nerve grafts. In 21 rabbits the saphenous
      nerve was used as a nerve graft and coapted to the cut motor nerve of vastus
      medialis. The animals were separated into three groups with different graft
      lengths, namely 3, 5, and 7 cm. In a second stage the distal end of the graft
      (Graft.dist.) was coapted to the motor branch of rectus femoris. Cross sections
      of the normal vastus nerve and the Graft.dist. before and 7 months after the
      connection to rectus femoris were analyzed histomorphometrically. Before
      coaptation to the target organ mean fiber number in the Graft.dist. of the 3-cm
      long grafts was 3380 and decreased to 2413 in the 7-cm-long grafts. Seven months
      after coaptation the results showed a statistically significant decrease of
      fibers in the Graft.dist. of group two and three and a distinct decrease of the
      fibers in group one. Summarizing, in a two-stage nerve grafting procedure the
      reinnervation of the muscle target organ leads to a down-regulation of fibers in
      the distal end of short and long nerve grafts.

PMID- 9572242
TI  - Characterization of the relationship between motor end-plate jitter and the
      safety factor.
AB  - A mathematical model developed for a personal computer was used to simulate the
      jitter phenomenon in neuromuscular transmission in order to characterize the
      relationship between jitter and the safety factor. Four models of normal and
      abnormal neuromuscular transmission were investigated. In a human experiment, the
      mean consecutive difference (MCD) values for stimulated single-fiber
      electromyography at firing rates of 1, 2, 5, and 10 Hz were measured in 137 motor
      end-plates of myasthenic patients. Results of the computer simulations show that
      the relationship between jitter and the safety factor is exponential like.
      Variations in jitter are most prominent in end-plates with low safety factors.
      This relationship agrees with results of human end-plate studies. Changes in the
      MCD values caused by presynaptic depression or facilitation are linearly
      correlated to the initial jitter, whereas the logarithmic values of MCD are not.
      It is very important to keep in mind this nonlinear relationship when relating
      single-fiber jitter to the safety factor.

PMID- 9572243
TI  - Mitochondrial abnormalities in selenium-deficient myopathy.
AB  - We report a man who developed selenium-deficient myopathy during long-term
      parenteral nutrition. Muscle biopsy showed marked mitochondrial depletion in the
      deep sarcoplasm and enlarged mitochondria at the periphery mainly in type 2
      fibers. Muscle weakness improved gradually after the second course of selenium
      supplementation. The peculiar mitochondrial abnormalities in muscle fibers appear
      to play a key role in the pathogenesis of selenium-deficient myopathy.

PMID- 9572244
TI  - Cervical paraspinal muscle abnormalities and symptom duration: a multivariate
      analysis.
AB  - The purpose of this study was to determine whether paraspinal and other major
      proximal and distal muscle spontaneous activity (SA) is related to cervical
      radiculopathy (CR) symptom duration. A multivariate analysis of 124
      (retrospectively identified) electrodiagnostically confirmed CRs was used to test
      these hypotheses. The results showed no evidence of correlation between SA and
      symptom duration for any of the upper limb muscles analyzed.

PMID- 9572245
TI  - The use of botulinum toxin in localizing neuromyotonia to the terminal branches
      of the peripheral nerve.
AB  - In 2 patients with neuromyotonia, nerve blocks had no effect on the abnormal
      activity, while intramuscular injection of the botulinum toxin abolished the
      discharges in one and greatly diminished them in the other. Botulinum toxin thus
      helps to localize the origin of the neuromyotonic discharges to the terminal
      regions of the peripheral nerve in those cases where the more proximal portions
      cannot be held responsible.

PMID- 9572246
TI  - Medial antebrachial cutaneous sensory studies in the evaluation of neurogenic
      thoracic outlet syndrome.
AB  - Over 3 years, we studied 8 patients with neurogenic thoracic outlet syndrome
      (TOS) and tested the medial antebrachial sensory response (MASR) to determine its
      diagnostic value. The MASR and ulnar sensory response (USR) were abnormal in all
      8 patients. Seven had a low median motor response (MMR) with a low USR. In 1, the
      MASR and USR were abnormal but the MMR was normal. We conclude that the MASR is
      of diagnostic value in patients with neurogenic TOS.

PMID- 9572247
TI  - Hypophosphatemia-induced neuropathy: clinical and electrophysiologic findings.
AB  - Severe hypophosphatemia has rarely been reported as a cause of acute paralysis.
      We present the clinical and electrophysiological findings on a patient who
      developed quadriparesis following several surgeries for complicated
      cholecystectomy. The paralysis was most likely the result of severe
      hypophosphatemia causing a neuropathy which improved readily after proper
      phosphate replacement. The possible pathogenic mechanisms of hypophosphatemic
      neuropathy are discussed.

PMID- 9572248
TI  - Evaluating motor end-plate-targeted injections of botulinum toxin type A in a
      canine model.
AB  - Tarsal joint forces were measured in dogs over 70 days following botulinum toxin
      type A (BTX-A) injections. Three dogs were injected at motor end-plates located
      by electromyography (EMG), while 3 dogs were similarly injected, but without EMG
      guidance. Extension forces were significantly (P < 0.05) smaller in limbs
      injected at motor end-plates than in corresponding limbs on days 14 and 35. There
      were no significant differences at other times. Using these techniques, EMG end
      plate targeting potentiates effects of BTX-A.

PMID- 9572249
TI  - Bilateral fibrolipomatous hamartoma of the median nerve with macrocheiria and
      late-onset nerve entrapment syndrome.
AB  - The case of a 46-year-old man is reported who presented with an extraordinary
      constellation of fibrolipomatous hamartomas of the right ulnar and both median
      nerves, with a right-sided giant hand ("macrocheiria") due to enlarged bones and
      subcutaneous tissue, and unusual late manifestation of nerve entrapment at the
      right wrist. Magnetic resonance imaging of the hypertrophied nerves disclosed
      large nerve fascicles surrounded by fibrous tissue, which allowed preoperative
      diagnosis.

PMID- 9572250
TI  - Further observations on forearm flexor weakness in inclusion body myositis.
AB  - In order to further characterize and provide a possible mechanism for the
      asymmetrical involvement of forearm muscles in inclusion body myositis (IBM), we
      measured isometric hand and pinch grip strength, and forearm muscle girth on 15
      IBM patients. Forearm muscle strength and girth were significantly greater on the
      dominant versus nondominant side: mean grip strength, 173.9 vs. 98.8 N; mean
      pinch strength, 47.6 vs. 29.7 N; and mean forearm girth, 22.5 vs. 19.9 cm. This
      observation may suggest a role for exercise in delaying the disease progression
      in IBM.

PMID- 9572251
TI  - Functional involvement of cerebral cortex in Duchenne muscular dystrophy.
AB  - Transcranial stimulation was performed in 4 patients with Duchenne muscular
      dystrophy and 4 control subjects. The patients' central motor conduction time was
      normal. The threshold for evoking electromyographic responses using electrical
      anodal stimulation was the same in both groups, but the threshold for stimulation
      with a circular magnetic coil at the vertex was higher in the patients. This is
      compatible with reduced cortical excitability that may be related to the
      deficiency of brain synaptic dystrophin.

PMID- 9572252
TI  - Effect of chloroquine-induced myopathy on rat soleus muscle sarcoplasm and
      expression of clathrin.
AB  - Clathrin-coated vesicles are involved in receptor-mediated intracellular
      transport pathways related to lysosomal proteolysis. Clathrin levels were
      significantly elevated in denervated soleus muscles from chloroquine- and saline
      treated rats as compared with their contralateral, innervated muscles. No
      difference was found in the clathrin levels of the denervated muscles in both
      groups. The accumulation of autophagic vacuoles was marked only in chloroquine
      treated muscles after denervation. These findings suggest that chloroquine does
      not inhibit intracellular trafficking of clathrin-coated vesicles during the
      overdevelopment of autophagic vacuoles.

PMID- 9572253
TI  - Guillain-Barre syndrome after Cyclospora infection.
AB  - We present a patient who developed Guillain-Barre syndrome (GBS) after a
      Cyclospora-induced diarrheal illness. We raise the possibility that Cyclospora is
      an infectious trigger for GBS in this patient. An active search for this agent in
      patients with GBS preceded by diarrheal illness is recommended.

PMID- 9572254
TI  - Acquired neuromyotonia in a patient with spinal epidural abscess.
AB  - We report a case of acquired neuromyotonia in a patient with Staphylococcus
      aureus septicemia and a spinal epidural abscess. Autoantibodies to voltage-gated
      potassium channels, which are associated with acquired neuromyotonia, were
      present during the patient's acute illness but became undetectable on clinical
      recovery. The spinal epidural abscess may have triggered the production of these
      specific autoantibodies, resulting in clinically and electromyographically
      detectable neuromyotonia.

PMID- 9572255
TI  - Palmaris brevis sign in ulnar neuropathy 1998.
AB  - A case of ulnar neuropathy, selectively affecting the deep branch and showing
      positive palmaris brevis sign, is reported. The palmaris brevis muscle was not
      only intact, but also showed excessive cocontraction with abductor digiti minimi.
      Palmaris brevis sign, when present, is useful in clinically localizing the site
      of the ulnar nerve lesion.

PMID- 9572256
TI  - Autonomic evaluation by means of standard tests and power spectral analysis in
      multiple sclerosis.

PMID- 9572257
TI  - Autonomic nervous system testing.

PMID- 9572258
TI  - Ritonavir-associated myasthenia gravis.

PMID- 9572259
TI  - Genetic heterogeneity of myoclonus epilepsy with ragged-red fibers syndrome.

PMID- 9572260
TI  - Chronic inflammatory demyelinating polyneuropathy with high titer of anti
      sulfated glucuronyl paragloboside antibody.

PMID- 9572261
TI  - CNS drug design based on principles of blood-brain barrier transport.
AB  - Lipid-soluble small molecules with a molecular mass under a 400-600-Da threshold
      are transported readily through the blood-brain barrier in vivo owing to lipid
      mediated transport. However, other small molecules lacking these particular
      molecular properties, antisense drugs, and peptide-based pharmaceuticals
      generally undergo negligible transport through the blood-brain barrier in
      pharmacologically significant amounts. Therefore, if present day CNS drug
      discovery programs are to avoid termination caused by negligible blood-brain
      barrier transport, it is important to merge CNS drug discovery and CNS drug
      delivery as early as possible in the overall CNS drug development process.
      Strategies for special formulation that enable drug transport through the blood
      brain barrier arise from knowledge of the molecular and cellular biology of blood
      brain barrier transport processes.

PMID- 9572262
TI  - Molecular cloning and expression of a mouse brain cDNA encoding a novel protein
      target of calcyclin.
AB  - A protein target of mouse calcyclin, p30, which we call calcyclin-binding protein
      (CacyBP), was identified in mouse brain and Ehrlich ascites tumor (EAT) cells.
      The amino acid sequence of the CacyBP chymotryptic peptide was used to prepare
      synthetic oligonucleotides that served as a probe to screen the mouse brain cDNA
      library. A 1.4-kb positive clone was detected, isolated, and sequenced. The
      analyzed clone contains an open reading frame encoding a protein of a molecular
      mass of approximately 26 kDa. The nucleotide and predicted amino acid sequences
      indicate that CacyBP is a novel protein. The results obtained from northern blots
      show that the CacyBP gene is expressed predominantly in mouse brain and EAT
      cells. Using a pGEX vector the recombinant CacyBP was expressed in Escherichia
      coli, and its properties were analyzed. The recombinant protein interacts with
      calcyclin at a physiologically relevant range of Ca2+ in solution during affinity
      chromatography and on blots. Because CacyBP, like calcyclin, is present in the
      brain, the interaction of these two proteins might be involved in calcium
      signaling pathways in neuronal tissue.

PMID- 9572263
TI  - The use of DNase I hypersensitivity site mapping to identify regulatory regions
      of the human cholinergic gene locus.
AB  - The DNase I hypersensitive sites of the human cholinergic gene locus, where both
      the choline acetyltransferase gene and the vesicular acetylcholine transporter
      gene are located, were analyzed to detect potential regulatory elements involved
      in cholinergic-specific transcriptional activation. From this analysis, seven
      cholinergic cell line-specific DNase I hypersensitive sites were found. The
      majority of these sites correspond to active promoter regions of the gene,
      including the promoter region of the vesicular acetylcholine transporter gene and
      the R, N, and M exons of the choline acetyltransferase gene. Two DNase I
      hypersensitive sites were identified in two noncholinergic cell lines, HeLa and
      MCF-7. One corresponds to a previously observed non-cell-specific enhancer,
      whereas the other corresponds to a previously described neuronal restrictive
      silencer element, NRSE. The NRSE has been shown to repress expression of various
      neuron-specific genes, not restricted to cholinergic-specific genes, in
      nonneuronal cells. This element can account for repression of the cholinergic
      gene locus in nonneuronal cells but does not account for repression in
      noncholinergic neurons. In addition, the chromatin boundary domain of the
      cholinergic gene locus, which possibly corresponds to the end of the
      transcription unit, was identified.

PMID- 9572264
TI  - A DEVD-inhibited caspase other than CPP32 is involved in the commitment of
      cerebellar granule neurons to apoptosis induced by K+ deprivation.
AB  - Cultured cerebellar granule neurons undergo apoptosis when switched from a medium
      containing depolarizing levels of K+ (25 mM KCl) to medium containing lower
      levels of K+ (5 mM KCl). We used this paradigm to investigate the role of
      caspases in the death process. Two broad-spectrum caspase inhibitors, tert
      butoxycarbonyl-Asp x (O-methyl) x fluoromethyl ketone and benzyloxycarbonyl-Val
      Ala-Asp x fluoromethyl ketone, significantly reduced cell death (90 and 60%,
      respectively) at relatively low concentrations (10-25 microM), suggesting that
      caspase activation is involved in the apoptotic process. DNA fragmentation, a
      hallmark of apoptosis, was also reduced by these caspase inhibitors, suggesting
      that caspase activation occurred upstream of DNA cleavage in the sequence of
      events leading to cell death. As a step toward identifying the caspase(s)
      involved, the effects of N-acetyl Tyr-Val-Ala-Asp x chloromethyl ketone (YVAD x
      cmk), an interleukin-1beta converting enzyme-preferring inhibitor, and N-acetyl
      Asp-Glu-Val-Asp x fluoromethyl ketone (DEVD x fmk), a CPP32-preferring inhibitor,
      were also evaluated. YVAD x cmk provided only modest (<20%) protection and only
      at the highest concentration (100 microM) tested, suggesting that interleukin
      1beta converting enzyme and/or closely related caspases were not involved. In
      comparison, DEVD x fmk inhibited cell death by up to 50%. Western blot analyses,
      however, failed to detect an increase in processing/activation of CPP32 or in the
      proteolysis of a CPP32 substrate, poly(ADP-ribose) polymerase, during the
      induction of apoptosis in granule neurons. Similarly, the levels of Nedd2, a
      caspase that is highly expressed in the brain and that is partially inhibited by
      DEVD x fmk, also remained unaffected in apoptotic neurons undergoing apoptosis.
      These results suggest that a DEVD-sensitive caspase other than CPP32 or Nedd2
      mediates the induction of apoptosis in K+-deprived granule neurons.

PMID- 9572265
TI  - Evidence for kappa- and mu-opioid receptor expression in C6 glioma cells.
AB  - The astrocytoma cell line rat C6 glioma has been used as a model system to study
      the mechanism of various opioid actions. Nevertheless, the type of opioid
      receptor(s) involved has not been established. Here we demonstrate the presence
      of high-affinity U69,593, endomorphin-1, morphine, and beta-endorphin binding in
      desipramine (DMI)-treated C6 cell membranes by performing homologous and
      heterologous binding assays with [3H]U69,593, [3H]morphine, or 125I-beta
      endorphin. Naive C6 cell membranes displayed U69,593 but neither endomorphin-1,
      morphine, nor beta-endorphin binding. Cross-linking of 125I-beta-endorphin to C6
      membranes gave labeled bands characteristic of opioid receptors. Moreover, RT-PCR
      analysis of opioid receptor expression in control and DMI-treated C6 cells
      indicate that both kappa- and mu-opioid receptors are expressed. There does not
      appear to be a significant difference in the level of mu nor kappa receptor
      expression in naive versus C6 cells treated with DMI over a 20-h period.
      Collectively, the data indicate that kappa- and mu-opioid receptors are present
      in C6 glioma cells.

PMID- 9572266
TI  - The nitric oxide-cyclic GMP pathway plays an essential role in both promoting
      cell survival of cerebellar granule cells in culture and protecting the cells
      against ethanol neurotoxicity.
AB  - NMDA has two beneficial effects on primary neuronal cultures of cerebellar
      granule cells (CGCs) established from 10-day-old rat pups. First, NMDA is
      neurotrophic and will enhance survival of CGCs in culture in the absence of
      ethanol. Second, ethanol exposure will induce cell death in CGC cultures, and
      NMDA can lessen this ethanol-induced cell loss, i.e., NMDA is neuroprotective.
      Because NMDA can stimulate production of nitric oxide (NO), which can in turn
      enhance synthesis of cyclic GMP, this study tested the hypothesis that the NO
      cyclic GMP pathway is essential for NMDA-mediated neurotrophism and
      neuroprotection. Inhibiting the synthesis of NO with N(G)-nitro-L-arginine methyl
      ester eliminated both the NMDA-mediated neurotrophic and neuroprotective effects.
      Similarly, inhibiting production of cyclic GMP with the agent LY83583 also
      abolished these effects. The NO generator 2,2'-(hydroxynitrosohydrazono)
      bisethanamine produced neurotrophic and neuroprotective effects that were similar
      to those induced by NMDA. Also, 8-bromo-cyclic GMP produced neurotrophic and
      neuroprotective effects that were quite similar to the effects produced by NMDA.
      In conclusion, NMDA enhances survival of cerebellar granule cells and protects
      the cells against ethanol-induced cell death by a mechanism(s) that involves the
      NO-cyclic GMP pathway.

PMID- 9572267
TI  - Palmitoylation of neurofascin at a site in the membrane-spanning domain highly
      conserved among the L1 family of cell adhesion molecules.
AB  - This report presents the first evidence that a member of the L1 family of nervous
      system cell-adhesion molecules is covalently modified by thioesterification with
      palmitate, and identifies a highly conserved cysteine in the predicted membrane
      spanning domain as the site of modification. Neurofascin is constitutively
      palmitoylated at cysteine-1213 at close to a 1:1 molar stoichiometry. Kinetics of
      palmitate incorporation into neurofascin expressed in resting neuroblastoma cells
      indicate that the palmitate modification has the same turnover rate as the
      polypeptide chain and does not affect the protein stability of neurofascin.
      Palmitoylation of neurofascin expressed in dorsal root ganglion neurons is not
      required for delivery of neurofascin to the plasma membrane or targeting to
      axons. Palmitoylation also has no effect on ankyrin-binding activity of
      neurofascin, on the oligomeric state of neurofascin in solution, or on cell
      adhesion activity of neurofascin expressed in neuroblastoma cells. A significant
      difference between native and C1213L neurofascin is that these proteins were
      localized in distinct fractions within a low-density membrane population enriched
      in signaling molecules. These results indicate a palmitate-dependent targeting of
      neurofascin to a specialized membrane microdomain.

PMID- 9572268
TI  - Inorganic Pi increases neuronal survival in the acute early phase following
      excitotoxic/oxidative insults.
AB  - Inorganic phosphate (Pi) plays a vital role in intracellular energy metabolism.
      Its many effects include stimulation of glucose use, enhancement of high-energy
      phosphate concentrations, and modulation of cytosolic free [Ca2+]. Cultured fetal
      rat cortical neurons constitutively import Pi, and cytosolic levels positively
      correlate with [ATP], [NADPH], and energy charge. In the present study, we
      demonstrate that the concentration of intracellular Pi is an important
      determinant of acute neuronal survival after an excitotoxic or oxidative insult
      to cultured fetal rat cortical neurons. Extracellular Pi dose-dependently
      enhanced survival of cortical neurons after exposure to NMDA at early (< or = 6
      h) time points after termination of the insult. Pi similarly increased neuronal
      survival after exposure to kainic acid or H2O2. Pi-exposed neurons had higher
      basal intracellular [Pi], [ATP], and [GSH], and slightly lower cytosolic free
      [Ca2+], compared with Pi-deprived neurons. Pi-exposed neurons maintained
      increased [ATP] after exposure to NMDA and displayed reduced formation of
      reactive oxygen species after exposure to kainic acid or H2O2, compared with Pi
      deprived neurons. These findings demonstrate that changes in extracellular and
      intracellular Pi can affect neuronal survival after excitotoxic or oxidative
      insults.

PMID- 9572269
TI  - Neurotrophins rescue cerebellar granule neurons from oxidative stress-mediated
      apoptotic death: selective involvement of phosphatidylinositol 3-kinase and the
      mitogen-activated protein kinase pathway.
AB  - Cerebellar granule neurons maintained in medium containing serum and 25 mM K+
      reliably undergo an apoptotic death when switched to serum-free medium with 5 mM
      K+. New mRNA and protein synthesis and formation of reactive oxygen intermediates
      are required steps in K+ deprivation-induced apoptosis of these neurons. Here we
      show that neurotrophins, members of the nerve growth factor gene family, protect
      from K+/serum deprivation-induced apoptotic death of cerebellar granule neurons
      in a temporally distinct manner. Switching granule neurons, on day in vitro (DIV)
      4, 10, 20, 30, or 40, from high-K+ to low-K+/serum-free medium decreased
      viability by >50% when measured after 30 h. Treatment of low-K+ granule neurons
      at DIV 4 with nerve growth factor, brain-derived neurotrophic factor (BDNF),
      neurotrophin-3, or neurotrophin-4/5 (NT-4/5) demonstrated concentration-dependent
      (1-100 ng/ml) protective effects only for BDNF and NT-4/5. Between DIV 10 and 20,
      K+-deprived granule neurons showed decreasing sensitivity to BDNF and no response
      to NT-4/5. Cerebellar granule neuron death induced by K+ withdrawal at DIV 30 and
      40 was blocked only by neurotrophin-3. BDNF and NT-4/5 also circumvented
      glutamate-induced oxidative death in DIV 1-2 granule neurons. Granule neuron
      death caused by K+ withdrawal or glutamate-triggered oxidative stress was,
      moreover, limited by free radical scavengers like melatonin. Neurotrophin
      protective effects, but not those of antioxidants, were blocked by selective
      inhibitors of phosphatidylinositol 3-kinase or the mitogen-activated protein
      kinase pathway, depending on the nature of the oxidant stress. These observations
      indicate that the survival-promoting effects of neurotrophins for central
      neurons, whose cellular antioxidant defenses are challenged, require activation
      of distinct signal transduction pathways.

PMID- 9572270
TI  - Intermediate filament disassembly in cultured dorsal root ganglion neurons is
      associated with amino-terminal head domain phosphorylation of specific subunits.
AB  - We previously reported that activation of protein kinase A in cultured rat dorsal
      root ganglion neurons, treated concomitantly with low concentrations of okadaic
      acid that selectively inhibit protein phosphatase-2A, enhanced the Triton X-100
      solubility of neurofilament triplet proteins. We now show that peripherin and
      alpha-internexin follow the same fragmentation profile as the neurofilament
      subunits, consistent with the notion that all five cytoplasmic intermediate
      filament proteins in these neurons form an integrated filamentous network whose
      assembly can be modulated by protein kinase A. Similar to the situation
      previously observed for the light neurofilament subunit, there was a strong
      correlation between phosphorylation of the amino-terminal head domain of
      peripherin and filament fragmentation. In contrast, insignificant levels of 32P
      were incorporated into alpha-internexin under conditions promoting disassembly,
      indicating that phosphorylation of this protein is not involved directly in
      filament fragmentation. The situation for the mid-sized neurofilament subunit
      (NFM) was not as clear-cut. Phosphopeptide mapping of NFM revealed many head and
      tail domain phosphorylation sites. However, changes in NFM head domain
      phosphorylation under conditions promoting filament disassembly were not as
      pronounced as for peripherin.

PMID- 9572271
TI  - The transcription factor NF-kappaB mediates increases in calcium currents and
      decreases in NMDA- and AMPA/kainate-induced currents induced by tumor necrosis
      factor-alpha in hippocampal neurons.
AB  - Tumor necrosis factor-alpha (TNF alpha) is a cytokine rapidly produced in the
      brain in response to vigorous neuronal activity and tissue injury. TNF alpha may
      protect neurons against excitotoxic and oxidative insults by a mechanism
      involving activation of the transcription factor NF-kappaB. Whole-cell perforated
      patch clamp recordings in cultured rat hippocampal neurons showed that long-term
      treatment (24-48 h) with TNF alpha increases Ca2+ current density;
      pharmacological analysis indicated a major increase in current through L-type
      voltage-dependent calcium channels. Long-term treatment with TNF alpha caused a
      decrease in currents induced by glutamate, NMDA, AMPA, and kainate. Shorter
      exposures to TNF alpha (acute; 2 h) did not alter Ca2+ current or glutamate
      receptor agonist-induced currents. Ceramide, an intracellular messenger that
      activates the transcription factor NF-kappaB, mimicked the actions of TNFs on
      Ca2+ current density and currents induced by glutamate receptor agonists.
      Cotreatment with kappaB decoy DNA abolished the effects of TNF alpha on Ca2+
      current and excitatory amino acid-induced currents, demonstrating a requirement
      for NF-kappaB activation in the actions of TNF alpha. Neurons pretreated with TNF
      alpha exhibited increased intracellular Ca2+ concentrations following membrane
      depolarization but reduced intracellular Ca2+ concentration responses to
      excitatory amino acids, compared with neurons in untreated control cultures or
      cultures cotreated with kappaB decoy DNA. These findings suggest important roles
      for the transcription factor NF-kappaB in modulation of voltage-dependent calcium
      channels and glutamate receptors and the many physiological and
      pathophysiological processes in which these ion channels are involved. Such
      signaling mechanisms may be particularly important in injury settings such as
      ischemia or trauma, where TNF alpha expression is increased and NF-kappaB is
      activated.

PMID- 9572272
TI  - Activated transcription of the human neuropeptide Y gene in differentiating SH
      SY5Y neuroblastoma cells is dependent on transcription factors AP-1, AP-2alpha,
      and NGFI.
AB  - Activated transcription of the human neuropeptide Y gene (NPY) was investigated
      in SH-SY5Y neuroblastoma cells at the onset of sympathetic neuronal
      differentiation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) and serum
      or by nerve growth factor (NGF). As determined by transient expression, two NGF
      response elements (REs) were required for transcription induced by NGF in SH-SY5Y
      cells with stable expression of an exogenous NGF receptor TRK-A gene (SH
      SY5Y/trk). TPA treatment in the presence of serum induced NPY transcription in
      both wild-type SH-SY5Y (SH-SY5Y/wt) and SH-SY5Y/trk cells. A TPA RE (TRE),
      overlapping the proximal NGF RE, was identified by expression of the v-Jun
      oncoprotein that enhanced NPY transcription. Suppression of TPA-induced NPY
      transcription was obtained by expression of a dominant negative Jun protein,
      selective protein kinase C inhibition, or introduction of a mutated TRE, whereas
      NGF-induced NPY transcription was inhibited to a lesser degree. The transcription
      factor AP-2alpha was shown to bind cooperatively to the NPY promoter with either
      AP-1 or NGFI-A to the shared TRE and NGF RE and to the distal NGF RE,
      respectively. These results show that transcription factors AP-1, AP-2alpha, and
      NGFI-A are involved in activated NPY transcription during the onset of neuronal
      differentiation.

PMID- 9572274
TI  - NMDA receptor stimulation selectively initiates GABA(A) receptor delta subunit
      mRNA expression in cultured rat cerebellar granule neurons.
AB  - Findings in vivo and in culture suggest that neuronal activity selectively
      regulates GABA(A) receptor delta subunit mRNA expression in cerebellar granule
      neurons. For example, the onset of delta subunit mRNA expression during postnatal
      maturation coincides with innervation. Furthermore, depolarizing conditions (25
      mM KCl) in culture initiate and maintain increases in the delta subunit
      transcript level. We have now examined whether similar changes in delta subunit
      mRNA expression occur in cultured neurons after activation of glutamate receptors
      of the NMDA subtype, an event that mimics granule neuron depolarization by mossy
      fiber innervation in vivo. Our studies demonstrate that addition of 50 microM
      NMDA to cultured rat granule neurons maintained in defined, serum-free medium
      specifically initiates delta subunit transcript expression. Whereas the level of
      the delta subunit mRNA is increased fourfold by this treatment, levels of other
      GABA(A) receptor subunit transcripts are not significantly changed. The level of
      the delta subunit transcript is further increased when NMDA receptor activation
      is enhanced by maintaining neurons in a Mg2+-free medium to alleviate Mg2+
      blockade of the receptor channel. The NMDA-induced elevation in delta subunit
      transcript expression involves activation of a Ca2+/calmodulin-dependent protein
      kinase pathway. These findings suggest that activation of an excitatory pathway
      may regulate the expression of an inhibitory receptor phenotype in cerebellar
      granule neurons in vivo.

PMID- 9572273
TI  - Up-regulation of NR2B subunit of NMDA receptors in cerebellar granule neurons by
      Ca2+/calmodulin kinase inhibitor KN93.
AB  - Recordings of NMDA-activated currents from cerebellar granule neurons in culture
      revealed a developmental increase in current density accompanied by a slight
      decrease of the half-maximal effective concentration. At the same time, a
      decrease of NMDA receptors comprising NR2B subunits was demonstrated by the
      reduction in the antagonism of NMDA currents by ifenprodil. Ifenprodil antagonism
      increased after treatment for 24 h with KN93- and KN62-selective inhibitors of
      the Ca2+/calmodulin-dependent protein kinases (CaM kinases), indicating a
      selective increase of receptor containing NR2B subunit. This increase was
      observed at all ages tested: 4 days in vitro (DIV4), DIV6, and DIV13. Western
      blot analysis with specific NMDA receptor antibodies performed at DIV6 confirmed
      the electrophysiological data. At this age, the negative control KN92 was
      ineffective. The increasing ifenprodil antagonism after KN93 treatment was
      proportionally greater in cells at DIV13 than at DIV4. Treatment with NMDA (100
      microM) of cerebellar cultures for 24 h produced a decrease in the NMDA-induced
      current density by almost 50% at all ages tested. Ifenprodil antagonism, however,
      was unchanged. We propose that the expression of NR2B subunits in cerebellar
      granule cells is selectively stimulated by the inhibition of CaM kinases.

PMID- 9572275
TI  - Ultrastructural studies of carboxyl-terminal truncation mutants of the neuronal
      intermediate filament protein peripherin.
AB  - We have prepared carboxyl-terminal truncation mutants of the neuronal
      intermediate filament (IF) protein peripherin and examined the assembly
      characteristics of these mutant proteins in SW13 cells in the presence and
      absence of vimentin. In the absence of vimentin, tailless peripherin protein (Per
      C424) self-assembles into bundles and clumps as observed by immunofluorescence,
      whereas a peripherin mutant that is missing the tail as well as a small portion
      of the rod (Per-C356) appears as spherical aggregates. Similar phenotypes are
      observed when vimentin-positive cells are transfected with Per-C424 or Per-C356.
      In these cells, the entire IF network is disrupted, and vimentin colocalizes with
      the mutant peripherin proteins. To examine the morphology of the bundles and
      clumps formed by Per-C424 at the electron microscopic level, we prepared stable
      cell lines expressing different levels of this mutant protein. By
      immunofluorescence, Per-C424 appears as either clumps or bundles of filaments
      depending on the expression level of the mutant protein. However, under electron
      microscopy, it is apparent that both clumps and bundles are composed of tightly
      packed IFs. We were unable to obtain stable cell lines expressing Per-C356,
      indicating that this mutant may prevent cell proliferation. Using a vector
      containing an internal ribosomal entry site, we prepared a construct that
      expresses Per-C356 and green fluorescent protein as a single mRNA, and we were
      able to isolate cells that expressed Per-C356 by fluorescence-activated cell
      sorting. Electron microscopic analysis of these cells showed that these
      aggregates are solid and contain no obvious filamentous structures.

PMID- 9572276
TI  - Role of potassium channels in amyloid-induced cell death.
AB  - Basal forebrain cholinergic neurons are severely depleted early in Alzheimer's
      disease and appear particularly susceptible to amyloid beta-peptide (A beta)
      toxicity in vivo. To model this effect in vitro, a cholinergic septal cell line
      (SN56) was exposed to A beta. SN56 cells exhibited a tetraethylammonium (TEA)
      sensitive outward K+ current with delayed rectifier characteristics. Increases of
      64% (+/-19; p < 0.02) and 44% (+/-12; p < 0.02) in K+ current density were noted
      6-12 and 12-18 h following the addition of A beta to SN56 cell cultures,
      respectively. Morphological observation and staining for cell viability showed
      that 25 +/- 4 and 39 +/- 4% of SN56 cells were dead after 48- and 96-h exposures
      to A beta, respectively. Perfusion of SN56 cells with 10-20 mM TEA blocked 71 +/-
      6 to 92 +/- 2% of the outward currents, widened action potentials, elevated
      [Ca2+]i, and inhibited 89 +/- 14 and 68 +/- 14% of the A beta toxicity. High
      [K+]o, which depolarizes cell membranes and increases [Ca2+]i, also protected
      SN56 cells from A beta toxicity. This effect appeared specific since glucose
      deprivation of SN56 cells did not alter K+ current density and TEA did not
      protect these cells from hypoglycemic cell death. Furthermore, A beta was toxic
      to a dopaminergic cell line (MES23.5) that expressed a K+ current with delayed
      rectifier characteristics; K+ current density was not altered by A beta and
      MES23.5 cells were not protected by TEA from A beta toxicity. In contrast, a
      noncholinergic septal cell line (SN48) that shows minimal outward K+ currents was
      resistant to the toxicity of A beta. These data suggest that a K+ channel with
      delayed rectifier characteristics may play an important role in A beta-mediated
      toxicity for septal cholinergic cells.

PMID- 9572277
TI  - c-Fos deficiency inhibits induction of mRNA for some, but not all,
      neurotransmitter biosynthetic enzymes by immobilization stress.
AB  - Recent studies indicated that c-Fos protein may be mediating stress-elicited
      transcriptional activation of genes involved in neurotransmitter biosynthesis.
      However, direct evidence for c-Fos mediating these changes in gene expression has
      been lacking. Mice with disrupted c-fos gene (+/- or -/- genotypes) were used to
      examine the effect of immobilization stress on a group of stress-responsive
      genes. In male adrenals, c-Fos was found not essential for stress-elicited
      activation of expression of tyrosine hydroxylase, dopamine beta-hydroxylase
      (DBH), phenylethanolamine N-methyltransferase, or neuropeptide Y. In females,
      immobilization failed to induce adrenal DBH in the c-Fos-deficient mice. In
      brainstem, c-Fos was indispensable for elevation of DBH mRNA in both genders. The
      gene, gender, and tissue specificity in the requirement for c-Fos points to
      diversity in adaptation mechanisms to stress.

PMID- 9572278
TI  - Relationships between the catechol substrate binding site and amphetamine,
      cocaine, and mazindol binding sites in a kinetic model of the striatal
      transporter of dopamine in vitro.
AB  - Experiments were conducted to determine how (-)-cocaine and S(+)-amphetamine
      binding sites relate to each other and to the catechol substrate site on the
      striatal dopamine transporter (sDAT). In controls, m-tyramine and S(+)
      amphetamine caused release of dopamine from intracellular stores at
      concentrations > or = 12-fold those observed to inhibit inwardly directed sDAT
      activity for dopamine. In preparations from animals pretreated with reserpine, m
      tyramine and S(+)-amphetamine caused release of preloaded dopamine at
      concentrations similar to those that inhibit inwardly directed sDAT activity.
      S(+)-Amphetamine and m-tyramine inhibited sDAT activity for dopamine by competing
      for a common binding site with dopamine and each other, suggesting that
      phenethylamines are substrate analogues at the plasmalemmal sDAT. (-)-Cocaine
      inhibited sDAT at a site separate from that for substrate analogues. This site is
      mutually interactive with the substrate site (K(int) = 583 nM). Mazindol
      competitively inhibited sDAT at the substrate analogue binding site. The results
      with (-)-cocaine suggest that the (-)-cocaine binding site on sDAT is distinct
      from that of hydroxyphenethylamine substrates, reinforcing the notion that an
      antagonist for (-)-cocaine binding may be developed to block (-)-cocaine binding
      with minimal effects on dopamine transporter activity. However, a strategy of how
      to antagonize drugs of abuse acting as substrate analogues is still elusive.

PMID- 9572279
TI  - Biosynthesis and metabolism of native and oxidized neuropeptide Y in the
      hippocampal mossy fiber system.
AB  - Neuropeptide Y (NPY) gene expression is known to be modulated in the mossy fiber
      projection of hippocampal granule cells following seizure. We investigated NPY
      biosynthesis and metabolism in an attempt to characterize NPY biochemically as a
      neurotransmitter in the granule cell mossy fiber projection. NPY biosynthesis was
      compared in normal control animals and in animals that had experienced a single
      pentylenetetrazole-induced seizure. In situ hybridization analysis established
      the postseizure time course of preproNPY mRNA expression in the hippocampal
      formation, localizing the majority of increased preproNPY mRNA content to the
      hilus of the dentate gyrus. Radioimmunoassay analysis of the CA3/mossy fiber
      terminal subfield confirmed a subsequent increase in NPY peptide content.
      Biosynthesis of NPY peptide by granule cells and transport to the CA3/mossy fiber
      subfield was demonstrated by in vivo radiolabel infusion to the dentate
      gyrus/hilus followed by sequential HPLC purification of identified radiolabeled
      peptide from the CA3/mossy fiber terminal subfield. Additional in vivo
      radiolabeling studies revealed a postseizure increase in an unidentified NPY-like
      immunoreactive (NPY-LI) species. HPLC/radioimmunoassay analyses of CA3 subfield
      tissue extracts comparing normal control animals and pentylenetetrazole-treated
      animals confirmed the increased total NPY-LI, and demonstrated that the increased
      NPY-LI was comprised of a minor increase in native NPY and a major increase in
      the unknown NPY-LI. Data from subsequent and separate analyses incorporating
      immunoprecipitation with anti-C-terminal flanking peptide of NPY, further HPLC
      purification, and matrix-assisted laser desorption/ionization mass spectrometry
      support the conclusion that the unknown NPY-LI is methionine sulfoxide NPY. NPY
      and NPY-sulfoxide displayed differential calcium sensitivity for release from
      mossy fiber synaptosomes. Similar to NPY, NPY sulfoxide displayed high-affinity
      binding to each of the cloned Y1, Y2, Y4, and Y5 receptor subtypes. Postrelease
      inactivation of NPY was demonstrated in a mossy fiber synaptosomal preparation.
      Thus, the present study in combination with previously reported
      electrophysiological activity of NPY in the CA3 subfield demonstrates that NPY
      fulfills the classical criteria for a neurotransmitter in the hippocampal granule
      cell mossy fiber projection, and reveals the presence of two molecular forms of
      NPY that display differential mechanisms of release while maintaining similar
      receptor potencies.

PMID- 9572280
TI  - RGS7 attenuates signal transduction through the G(alpha q) family of
      heterotrimeric G proteins in mammalian cells.
AB  - The RGS proteins are a recently discovered family of G protein regulators that
      have been shown to act as GTPase-activating proteins (GAPs) on the G(alpha i) and
      G(alpha q) subfamilies of the heterotrimeric G proteins. Here, we demonstrate
      that RGS7 is a potent GAP in vitro on G(alpha i1), and G(alpha o) heterotrimeric
      proteins and that RGS7 acts to down-regulate G(alpha q)-mediated calcium
      mobilization in a whole-cell assay system using a transient expression protocol.
      This RGS protein and RGS4 are reported to be expressed predominantly in brain,
      and in situ hybridization studies have revealed similarities in the regional
      distribution of RGS and G(alpha q) mRNA expression. Our findings provide further
      evidence to support a functional role for RGS4 and RGS7 in G(alpha q)-mediated
      signaling in the CNS.

PMID- 9572281
TI  - Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote
      knockout mice.
AB  - The neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has
      been proposed to be attenuated by sequestration into intracellular vesicles by
      the vesicular monoamine transporter (VMAT2). The purpose of this study was to
      determine if mice with genetically reduced levels of VMAT2 (heterozygote
      knockout; VMAT2 +/-) were more vulnerable to MPTP. Striatal dopamine (DA)
      content, the levels of DA transporter (DAT) protein, and the expression of glial
      fibrillary acidic protein (GFAP) mRNA, a marker of gliosis, were assessed as
      markers of MPTP neurotoxicity. In all parameters measured VMAT2 +/- mice were
      more sensitive than their wild-type littermates (VMAT2 +/+). Administration of
      MPTP (7.5, 15, or 30 mg/kg, b.i.d.) resulted in dose-dependent reductions in
      striatal DA levels in both VMAT2 +/- and VMAT2 +/+ animals, but the neurotoxic
      potency of MPTP was approximately doubled in the VMAT2 +/- mice: 59 versus 23% DA
      loss 7 days after 7.5 mg/kg dose for VMAT2 +/- and VMAT2 +/+ mice, respectively.
      Dopaminergic nerve terminal integrity, as assessed by DAT protein expression,
      also revealed more drastic reductions in the VMAT2 +/- mice: 59 versus 35% loss
      at 7.5 mg/kg and 95 versus 58% loss at 15 mg/kg for VMAT2 +/- and VMAT2 +/+ mice,
      respectively. Expression of GFAP mRNA 2 days after MPTP was higher in the VMAT2
      +/- mice than in the wild-type: 15.8- versus 7.8-fold increase at 7.5 mg/kg and
      20.1- versus 9.6-fold at 15 mg/kg for VMAT2 +/- and VMAT2 +/+ mice, respectively.
      These observations clearly demonstrate that VMAT2 +/- mice are more susceptible
      to the neurotoxic effects of MPTP, suggesting that VMAT2-mediated sequestration
      of the neurotoxin into vesicles may play an important role in attenuating MPTP
      toxicity in vivo.

PMID- 9572282
TI  - Enhanced [3H]DOPA and [3H]dopamine turnover in striatum and frontal cortex in
      vivo linked to glutamate receptor antagonism.
AB  - We tested the hypothesis that blockade of NMDA glutamate receptors in brain
      enhances dopamine turnover. We blocked this class of glutamate receptors in the
      rat brain in vivo with dizocilpine (MK-801) and measured the accumulation of
      radiolabeled DOPA and its metabolites as functions of time after intravenous
      bolus injection. Using the time courses of the accumulated metabolites, we
      calculated the turnover constants of enzymes mediating dopamine synthesis and
      catabolism. Dizocilpine treatment for 8 days enhanced the rates of DOPA
      decarboxylation and dopamine oxidation (monoamine oxidation) 4- and 16-fold,
      respectively, in neostriatum and 10- and 3-fold, respectively, in frontal cortex.
      The findings are not inconsistent with the hypothesis that the psychotomimetic
      properties of dizocilpine may be the manifestation of denervation
      hypersensitivity linked to activation of key enzymes of dopamine turnover in
      striatum.

PMID- 9572283
TI  - 3-Hydroxybutyrate aids the recovery of the energy state from aglycaemic hypoxia
      of adult but not neonatal rat brain slices.
AB  - The level of phosphocreatine (PCr) and the intracellular pH (pHi) of superfused
      cortical brain slices from adult or 10-day-old rats were monitored using 31P NMR.
      When the glucose in the superfusing medium was replaced by 3-hydroxybutyrate
      (3HB), there was a significant reduction in PCr of the adult but not the neonatal
      slices. The level of PCr of the adult slices was reduced by a greater amount by
      aglycaemic hypoxia compared with the neonatal brain slices and pHi was decreased
      by the same amount. After aglycaemic hypoxia, the levels of PCr of the neonatal
      slices recovered to the same extent when perfused with glucose or 3HB alone or a
      mixture of glucose and 3HB. The recovery of the PCr was significantly more in the
      neonatal than the adult brain slices with glucose alone after aglycaemic hypoxia,
      whereas pHi returned to control levels in both tissue types and with all
      substrates. The relative recovery of the PCr of the adult slices after aglycaemic
      hypoxia was the same with either 3HB or glucose. However, if glucose and 3HB were
      applied together, recovery of PCr was significantly improved compared with
      glucose alone.

PMID- 9572284
TI  - M1 muscarinic agonist treatment reverses cognitive and cholinergic impairments of
      apolipoprotein E-deficient mice.
AB  - Recent studies suggest that apolipoprotein E (apoE) plays a specific role in
      brain cholinergic function and that the E4 allele of apoE (apoE4), a major risk
      factor for Alzheimer's disease (AD), may predict the extent of cholinergic
      dysfunction and the efficacy of cholinergic therapy in this disease. Animal model
      studies relevant to this hypothesis revealed that apoE-deficient (knockout) mice
      have working memory impairments that are associated with distinct dysfunction of
      basal forebrain cholinergic neurons. Cholinergic replacement therapy utilizing M1
      selective muscarinic agonists has been proposed as effective treatment for AD
      patients. In the present study, we examined whether the memory deficits and brain
      cholinergic deficiency of apoE-deficient mice can be ameliorated by the M1
      selective agonist 1-methylpiperidine-4-spiro-(2'-methylthiazoline), [AF150(S)].
      Treatment of apoE-deficient mice with AF150(S) for 3 weeks completely abolished
      their working memory impairments. Furthermore, this reversal of cognitive deficit
      was associated with a parallel increase of histochemically determined brain
      choline acetyltransferase and acetylcholinesterase levels and with the recovery
      of these cholinergic markers back to control levels. These findings show that
      apoE deficiency-related cognitive and cholinergic deficits can be ameliorated by
      M1-selective muscarinic treatment. They also provide a novel model system for
      development and evaluation of therapeutic strategies directed specifically at the
      AD patients whose condition is attributed to the apoE genotype.

PMID- 9572285
TI  - Oxindole, a sedative tryptophan metabolite, accumulates in blood and brain of
      rats with acute hepatic failure.
AB  - Rats treated with oxindole (10-100 mg/kg i.p.), a putative tryptophan metabolite,
      showed decreased spontaneous locomotor activity, loss of the righting reflex,
      hypotension, and reversible coma. Brain oxindole levels were 0.05 +/- 0.01 nmol/g
      in controls and increased to 8.1 +/- 1.7 or 103 +/- 15 nmol/g after its
      administration at doses of 10 or 100 mg/kg i.p., respectively. To study the role
      that oxindole plays in the neurological symptoms associated with acute liver
      failure, we measured the changes of its concentration in the brain after massive
      liver damage, and we investigated the possible metabolic pathways leading to its
      synthesis. Rats treated with either thioacetamide (0.2 and 0.4 g/kg i.p., twice)
      or galactosamine (1 and 2 g/kg i.p.) showed acute liver failure and a large
      increase in blood or brain oxindole concentrations (from 0.05 +/- 0.01 nmol/g in
      brains of controls to 1.8 +/- 0.3 nmol/g in brains of thioacetamide-treated
      animals). Administration of tryptophan (300-1,000 mg/kg p.o.) caused a twofold
      increase, whereas administration of indole (10-100 mg/kg p.o.) caused a 200-fold
      increase, of oxindole content in liver, blood, and brain, thus suggesting that
      indole formation from tryptophan is a limiting step in oxindole synthesis. Oral
      administration of neomycin, a broad-spectrum, locally acting antibiotic agent
      able to reduce intestinal flora, significantly decreased brain oxindole content.
      Taken together, our data show that oxindole is a neurodepressant tryptophan
      metabolite and suggest that it may play a significant role in the neurological
      symptoms associated with acute liver impairment.

PMID- 9572286
TI  - Involvement of calcineurin in Ca2+ paradox-like injury of cultured rat
      astrocytes.
AB  - The Ca2+/calmodulin-dependent phosphatase calcineurin may have physiological and
      pathological roles in neurons, but little is known about the roles of the enzyme
      in glial cells. We have previously reported that reperfusion of cultured
      astrocytes in Ca2+-containing medium after exposure to Ca2+-free medium caused
      Ca2+ influx followed by delayed cell death. In this study, we examined if
      calcineurin is involved in this Ca2+-mediated astrocytic injury. FK506, an
      inhibitor of calcineurin, protected cultured rat astrocytes against paradoxical
      Ca2+ challenge-induced injury in a dose-dependent manner (10(-10)-10(-8) M).
      Cyclosporin A at 1 microM mimicked the effect of FK506. Rapamycin (1 microM) did
      not affect astrocyte injury, but it blocked the protective effect of FK506.
      Deltamethrin (20 nM), another calcineurin inhibitor, had a similar protective
      effect, whereas okadaic acid did not. FK506 affected neither paradoxical Ca2+
      challenge-induced increase in cytosolic Ca2+ level nor Na+-Ca2+ exchange activity
      in the cells, suggesting that the calcineurin is involved in processes downstream
      of increased cytosolic Ca2+ level. Immunochemical studies showed that both
      calcineurin A (probably the A beta2 isoform) and B subunits were expressed in the
      cells. It is concluded that calcineurin is present in cultured astrocytes and it
      has a pathological role in the cells.

PMID- 9572287
TI  - Neuroprotective effects of NMDA receptor glycine recognition site antagonism:
      dependence on glycine concentration.
AB  - High-affinity NMDA receptor glycine recognition site antagonists protect brain
      tissue from ischemic damage. The neuroprotective effect of 5-nitro-6,7-dichloro
      2,3-quinoxalinedione (ACEA 1021), a selective NMDA receptor antagonist with
      nanomolar affinity for the glycine binding site, was examined in rat cortical
      mixed neuronal/glial cultures. ACEA 1021 alone did not alter spontaneous lactate
      dehydrogenase (LDH) release. Treatment with ACEA 1021 (0.1-10 microM) before 500
      microM glutamate, 30 microM NMDA, or 300 microM kainate exposure was found to
      reduce LDH release in a concentration-dependent fashion. These effects were
      altered by adding glycine to the medium. Glycine (1 mM) partially reversed the
      effect of ACEA 1021 on kainate cytotoxicity. Glycine (100 microM-1 mM) completely
      blocked the effects of ACEA 1021 on glutamate and NMDA cytotoxicity. The glycine
      concentration that produced a half-maximal potentiation of excitotoxin-induced
      LDH release in the presence of 1.0 microM ACEA 1021 was similar for glutamate and
      NMDA (18 +/- 3 and 29 +/- 9 microM, respectively). ACEA 1021 also reduced kainate
      toxicity in cultures treated with MK-801. The effects of glycine and ACEA 1021 on
      glutamate-induced LDH release were consistent with a model of simple competitive
      interaction for the strychnine-insensitive NMDA receptor glycine recognition
      site, although nonspecific effects at the kainate receptor may be of lesser
      importance.

PMID- 9572288
TI  - Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and
      GLAST) proteins in rat brain.
AB  - Excess activation of NMDA receptors is felt to participate in secondary neuronal
      damage after traumatic brain injury (TBI). Increased extracellular glutamate is
      active in this process and may result from either increased release or decreased
      reuptake. The two high-affinity sodium-dependent glial transporters [glutamate
      transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST)] mediate the
      bulk of glutamate transport. We studied the protein levels of GLT-1 and GLAST in
      the brains of rats after controlled cortical impact-induced TBI. With use of
      subtype-specific antibodies, GLT-1 and GLAST proteins were quantitated by
      immunoblotting in the ipsilateral and contralateral cortex at 2, 6, 24, 72, and
      168 h after the injury. Sham-operated rats served as control. TBI resulted in a
      significant decrease in GLT-1 (by 20-45%; p < 0.05) and GLAST (by 30-50%; p <
      0.05) protein levels between 6 and 72 h after the injury. D-[3H]Aspartate binding
      also decreased significantly (by 30-50%; p < 0.05) between 6 and 72 h after the
      injury. Decreased glial glutamate transporter function may contribute to the
      increased extracellular glutamate that may mediate the excitotoxic neuronal
      damage after TBI. This is a first report showing altered levels of glutamate
      transporter proteins after TBI.

PMID- 9572289
TI  - Regulation of nicotinic receptor subtypes following chronic nicotinic agonist
      exposure in M10 and SH-SY5Y neuroblastoma cells.
AB  - The present study further investigated whether nicotinic acetylcholine receptor
      (nAChR) subtypes differ in their ability to up-regulate following chronic
      exposure to nicotinic agonists. Seven nicotinic agonists were studied for their
      ability to influence the number of chick alpha4beta2 nAChR binding sites stably
      transfected in fibroblasts (M10 cells) following 3 days of exposure. The result
      showed a positive correlation between the Ki values for binding inhibition and
      EC50 values for agonist-induced alpha4beta2 nAChR up-regulation. The effects of
      epibatidine and nicotine were further investigated in human neuroblastoma SH-SY5Y
      cells (expressing alpha3, alpha5, beta2, and beta4 nAChR subunits). Nicotine
      exhibited a 14 times lower affinity for the nAChRs in SH-SY5Y cells as compared
      with M10 cells, whereas epibatidine showed similar affinities for the nAChRs
      expressed in the two cell lines. The nicotine-induced up-regulation of nAChR
      binding sites in SH-SY5Y cells was shifted to the right by two orders of
      magnitude as compared with that in M10 cells. The epibatidine-induced up
      regulation of nAChR binding sites in SH-SY5Y cells was one-fourth that in M10
      cells. The levels of mRNA of the various nAChR subunits were measured following
      the nicotinic agonist exposure. In summary, the various nAChR subtypes show
      different properties in their response to chronic stimulation.

PMID- 9572290
TI  - High-field proton magnetic resonance spectroscopy of a swine model for axonal
      injury.
AB  - A miniature swine model for diffuse brain injury has recently been developed that
      replicates the inertial loading conditions associated with rotational
      acceleration during automotive accidents. The swine model induces diffuse axonal
      pathology without macroscopic injury such as contusions and hematomas, thus
      affording a unique opportunity to study axonal injury with noninvasive techniques
      such as magnetic resonance imaging (MRI) and spectroscopy (MRS). In the present
      study, we evaluated this diffuse injury model with proton MRS, in vivo, using a
      high-field (4.0-T) MR scanner, since MRS has been demonstrated as a sensitive
      probe for detecting neurochemical abnormalities. Our study examined a region of
      the swine brain at timepoints before and after brain injury. Spectroscopic
      results indicate that N-acetylaspartate/creatine is diminished by at least 20% in
      regions of confirmed axonal pathology, whereas conventional MRI did not detect
      any abnormalities. These findings suggest that MRS has high sensitivity in
      diagnosing microscopic pathology following diffuse brain injury.

PMID- 9572291
TI  - Identification of cellular compartments involved in processing of cathepsin E in
      primary cultures of rat microglia.
AB  - Cathepsin E is a major nonlysosomal, intracellular aspartic proteinase that
      localizes in various cellular compartments such as the plasma membrane, endosome
      like organelles, and the endoplasmic reticulum (ER). To learn the segregation
      mechanisms of cathepsin E into its appropriate cellular destinations, the present
      studies were initiated to define the biosynthesis, processing, and intracellular
      localization as well as the site of proteolytic maturation of the enzyme in
      primary cultures of rat brain microglia. Immunohistochemical and immunoblot
      analyses revealed that cathepsin E was the most abundant in microglia among
      various brain cell types, where the enzyme existed predominantly as the mature
      enzyme. Immunoelectron microscopy studies showed the presence of the enzyme
      predominantly in the endosome-like vacuoles and partly in the vesicles located in
      the trans-Golgi area and the lumen of ER. In the primary cultured microglial
      cells labeled with [35S]methionine, >95% of labeled cathepsin E were represented
      by a 46-kDa polypeptide (reduced form) after a 30-min pulse. Most of it was
      proteolytically processed via a 44-kDa intermediate to a 42-kDa mature form
      within 4 h of chase. This processing was completely inhibited by bafilomycin A1,
      a specific inhibitor of vacuolar-type H+-ATPase. Brefeldin A, a blocker for the
      traffic of secretory proteins from the ER to the Golgi complex, also inhibited
      the processing of procathepsin E and enhanced its degradation. Procathepsin E,
      after pulse-labeling, showed complete susceptibility to endoglycosidase H,
      whereas the mature enzyme almost acquired resistance to endoglycosidases H as
      well as F. The present studies provide the first evidence that cathepsin E in
      microglia is first synthesized as the inactive precursor bearing high-mannose
      oligosaccharides and processed to the active mature enzyme with complex-type
      oligosaccharides via the intermediate form and that the final proteolytic
      maturation step occurs in endosome-like acidic compartments.

PMID- 9572292
TI  - Neuronal overexpression of heme oxygenase-1 correlates with an attenuated
      exploratory behavior and causes an increase in neuronal NADPH diaphorase
      staining.
AB  - Heme oxygenase isozymes, HO-1 (also known as hsp32) and HO-2, are the source for
      the formation of the putative messenger molecule carbon monoxide (CO), reactive
      iron, and the in vitro antioxidant bilirubin. We have developed and characterized
      transgenic (Tg) mice that overexpress the stress protein in neurons in various
      brain regions. The Tg mice were generated by the use of rat HO-1 cDNA under the
      control of the neuron-specific enolase promoter. Except for a tendency to have an
      enlarged spleen, Tg mice did not show gross anatomical changes. Increase in HO-1
      mRNA, which was demonstrated by northern blot analysis and in situ hybridization,
      was accompanied by an increase in neuronal HO-1 protein expression, shown by
      immunohistochemistry and western blotting, and an increase in HO activity.
      Expression of the transgene correlated with an attenuation of exploratory
      behavior and increased circling activity and coincided with enhanced neuronal
      NADPH diaphorase staining. Those changes were not accompanied by an increase in
      DNA damage or significant change in whole-brain NO synthase activity. The HO-1 Tg
      mice potentially represent a good model to examine the function of CO as a
      neuromodulator, iron as a gene regulator, and bile pigments as in vivo
      antioxidants.

PMID- 9572293
TI  - Nascent astrocyte particles differ from lipoproteins in CSF.
AB  - Little is known about lipid transport and metabolism in the brain. As a further
      step toward understanding the origin and function of CNS lipoproteins, we have
      characterized by size and density fractionation lipoprotein particles from human
      CSF and primary cultures of rat astrocytes. The fractions were analyzed for
      esterified and free cholesterol, triglyceride, phospholipid, albumin, and
      apolipoproteins (apo) E, AI, AII, and J. As determined by lipid and
      apolipoprotein profiles, gel electrophoresis, and electron microscopy, nascent
      astrocyte particles contain little core lipid, are primarily discoidal in shape,
      and contain apoE and apoJ. In contrast, CSF lipoproteins are the size and density
      of plasma high-density lipoprotein, contain the core lipid, esterified
      cholesterol, and are spherical. CSF lipoproteins were heterogeneous in
      apolipoprotein content with apoE, the most abundant apolipoprotein, localized to
      the largest particles, apoAI and apoAII localized to progressively smaller
      particles, and apoJ distributed relatively evenly across particle size. There was
      substantial loss of protein from both CSF and astrocyte particles after density
      centrifugation compared with gel-filtration chromatography. The differences
      between lipoproteins secreted by astrocytes and present in CSF suggest that in
      addition to delivery of their constituents to cells, lipoprotein particles
      secreted within the brain by astrocytes may have the potential to participate in
      cholesterol clearance, developing a core of esterified cholesterol before
      reaching the CSF. Study of the functional properties of both astrocyte-secreted
      and CSF lipoproteins isolated by techniques that preserve native particle
      structure may also provide insight into the function of apoE in the
      pathophysiology of specific neurological diseases such as Alzheimer's disease.

PMID- 9572294
TI  - Hydrogen peroxide enhances signal-responsive arachidonic acid release from
      neurons: role of mitogen-activated protein kinase.
AB  - Hydrogen peroxide (H2O2) is a potent stimulator of signal-responsive
      phospholipase A2 (PLA2) in vascular smooth muscle and cultured endothelial cells.
      We investigated whether H2O2 plays a similar regulatory role in neurons. H2O2 did
      not stimulate a release of arachidonic acid from cultured neurons when applied
      alone but strongly enhanced the liberation of arachidonic acid evoked by
      maximally effective concentrations of either glutamate, the glutamate receptor
      agonist N-methyl-D-aspartate (NMDA), the muscarinic receptor agonist carbachol,
      the Na+-channel opener veratridine, or the Ca2+-ionophore ionomycin. The
      potentiating effects of H2O2 were strongly inhibited in the presence of the PLA2
      inhibitor mepacrine, suggesting that the site of action was within the signal
      responsive arachidonic acid cascade. The enhancing effect of H2O2 was not
      reversed by protein kinase C inhibitors (chelerythrine chloride or GF 109203X)
      nor was it mimicked by phorbol ester treatment. H2O2 alone strongly enhanced the
      levels of immunodetectable activated mitogen-activated protein kinase (activated
      MAP kinases ERK1 and ERK2) in a Ca2+-dependent manner and this effect was
      additive with increases in the levels of activated MAP kinase evoked by
      glutamate. The enhanced release of arachidonic acid, however, was not clearly
      reversed by the MAP kinase kinase (MEK) inhibitor PD 98059, although this
      treatment effectively abolished H2O2 activation of MAP kinase. Thus, MAP kinase
      activation and Ca2+-dependent arachidonic acid release are regulated by oxidative
      stress in cultured striatal neurons.

PMID- 9572295
TI  - Functional coupling of the NK1 tachykinin receptor to phospholipase D in chinese
      hamster ovary cells and astrocytoma cells.
AB  - In [3H]myristic acid-prelabeled Chinese hamster ovary cells stably expressing the
      rat NK1 tachykinin receptor, the selective NK1 agonist [Pro9]substance P
      ([Pro9]SP) time and concentration dependently stimulated the formation of
      [3H]phosphatidylethanol in the presence of ethanol. This [Pro9]SP-induced
      activation of phospholipase D (PLD) was blocked by NK1 receptor antagonists and
      poorly or not mimicked by NK2 and NK3 agonists, respectively. In confirmation of
      previous observations, [Pro9]SP also stimulated the hydrolysis of
      phosphoinositides, the release of arachidonic acid, and the formation of cyclic
      AMP (cAMP). All these [Pro9]SP-evoked responses could be mimicked by aluminum
      fluoride, but they remained unaffected in cells pretreated with pertussis toxin,
      suggesting that a Gi/Go protein is not involved in these different signaling
      pathways. The activation of PLD by [Pro9]SP was sensitive to external calcium and
      required an active protein kinase C because the inhibition of this kinase (Ro 31
      8220) or its down-regulation (long-term treatment with a phorbol ester) abolished
      the response. In contrast, a cAMP-dependent process was not involved in the
      activation of PLD because the [Pro9]SP-evoked response was neither affected by Rp
      8-bromoadenosine 3',5'-cyclic monophosphorothioate nor mimicked by cAMP
      generating compounds (cholera toxin or forskolin) or by 8-bromo-cyclic AMP. A
      functional coupling of NK1 receptors to PLD was also demonstrated in the human
      astrocytoma cell line U 373 MG stimulated by SP or [Pro9]SP. These results
      suggest that PLD activation could be an additional signaling pathway involved in
      the mechanism of action of SP in target cells expressing NK1 receptors.

PMID- 9572296
TI  - Redistribution of imipramine from regions of the brain under the influence of
      circulating specific antibodies.
AB  - The kinetics of brain-to-blood redistribution of imipramine (IMI) was assessed in
      nine brain regions of control rats and rats given anti-tricyclic antidepressant
      (anti-TCA) antibody. Two antibodies were given intravenously 6 min after
      intravenous [3H]IMI (1 nmol/kg). One was a murine monoclonal IgG1 (Ka = 3.8 x
      10(7) M(-1)) at an IgG/IMI molar ratio of 1,000 (IgG1,000), and the other was a
      sheep polyclonal IgG (TAb; Ka = 1.3 x 10(10) M(-1)) at IgG/IMI molar ratios of 1,
      10, and 100 (TAb1, TAb10, and TAb100). In the control rats, IMI was rapidly taken
      up by the brain (Cmax at 5 min) with no significant differences among the brain
      regions (4.1 +/- 0.4 to 5.4 +/- 0.6 pmol/ g), and brain IMI then declined
      monoexponentially with a half-life of 44.2 min (cerebellum) to 77.3 min
      (hippocampus). The greatest IMI content was in the frontal cortex and the lowest
      in the cerebellum. The antibodies (except TAb1) stimulated the extent and rate of
      IMI redistribution from all the brain regions depending on the immunoreactive
      capacity (NKa) of the antibody. The antibody with the highest NKa (TAb100) had
      the greatest effect. The fraction of IMI removed from the brain was 58-74%, and
      the redistribution half-life was 7.9-15.6 min; the mean residence time was
      reduced by 66-75% (11.8-23.9 min). These results demonstrate that circulating
      anti-TCA IgG rapidly and reliably removes IMI from the brain, indicating that
      immunotoxicotherapy could be an efficient procedure for accelerating the removal
      of TCA from the brain.

PMID- 9572297
TI  - Implication of the first and third extracellular loops of the mu-opioid receptor
      in the formation of the ligand binding site: a study using chimeric mu
      opioid/angiotensin receptors.
AB  - Recent studies on chimeric mu/delta-, mu/kappa- and delta/kappa-opioid receptors
      have suggested that extracellular loops of the receptors were involved in the
      discriminatory binding of selective ligands by controlling their entry into the
      transmembrane binding site. Since homochimeric opioid receptors are mostly
      informative in terms of selectivity, the role of extracellular loops was examined
      here by studying heterochimeric mu receptors where the totality or parts of
      extracellular loops were replaced by the corresponding regions of the receptor
      for angiotensin II. Chimeric mu receptors with extracellular loop EL1 or EL3
      originating from the angiotensin receptor had 100-fold decreased affinities for
      opioids; the length of the first extracellular loop, which is one residue longer
      in angiotensin than mu receptors, was shown to be responsible for this situation.
      Substitution of the mu receptor second extracellular loop by that of the
      angiotensin receptor diminished by approximately 10-fold the affinities for
      opioids. Since all chimeras had altered affinities for selective and nonselective
      ligands, we propose that extracellular domains of the mu receptor, particularly
      the first and third loops, constrain the relative positioning of the connected
      transmembrane domains where selective as well as nonselective contact points form
      the opioid binding site.

PMID- 9572298
TI  - Calcium influx through AMPA receptors and through calcium channels is regulated
      by protein kinase C in cultured retina amacrine-like cells.
AB  - The functional modulation of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA) receptors by protein kinase C (PKC) was investigated
      in cultures enriched in retinal amacrine-like cells. The kainate-evoked [Ca2+]i
      increase is due to Ca2+ entry through open AMPA receptor channels, because it was
      blocked by the active isomer of a 2,3-benzodiazepine (LY 303070), an AMPA
      receptor antagonist. The AMPA receptor response to kainate was potentiated by
      phorbol 12-myristate 13-acetate, which specifically stimulates PKC, and it was
      decreased by bisindolylmaleimide I, a selective inhibitor of PKC, as well as by
      PKC down-regulation. The results indicate not only that the AMPA receptor
      activation has a PKC requirement, but also that PKC amplifies maximal receptor
      activation by 100 microM kainate. The effect of PKC activation or inhibition on
      voltage-gated Ca2+-channel activity was also investigated. Activation of PKC
      caused inhibition of Ca2+ channels, and the same effect was produced by
      inhibition of PKC, whereas the inactive analogue of the phorbol ester did not
      affect channel activity. Our results show an important role for PKC in regulating
      the function of both AMPA receptors and Ca2+ channels in cultured retina cells.

PMID- 9572300
TI  - Desensitization of the delta-opioid receptor correlates with its phosphorylation
      in SK-N-BE cells: involvement of a G protein-coupled receptor kinase.
AB  - Phosphorylation of G protein-coupled receptors is considered an important step
      during their desensitization. In SK-N-BE cells, recently presented as a pertinent
      model for the studies of the human delta-opioid receptor, pretreatment with the
      opioid agonist etorphine increased time-dependently the rate of phosphorylation
      of a 51-kDa membrane protein. Immunological characterization of this protein with
      an antibody, raised against the amino-terminal region of the cloned human delta
      opioid receptor, revealed that it corresponded to the delta-opioid receptor.
      During prolonged treatment with etorphine, phosphorylation increased as early as
      15 min to reach a maximum within 1 h. Phosphorylation and desensitization of
      adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the
      resensitization, a result strongly suggesting that phosphorylation of the delta
      opioid receptor plays a prominent role in its rapid desensitization. The increase
      in phosphorylation of the delta-opioid receptor, as well as its desensitization,
      was not affected by H7, an inhibitor of protein kinase A and protein kinase C,
      but was drastically reduced by heparin or Zn2+, known to act as G protein-coupled
      receptor kinase (GRK) inhibitors. These results are the first to show, on
      endogenously expressed human delta-opioid receptor, that a close link exists
      between receptor phosphorylation and agonist-promoted desensitization and that
      desensitization involves a GRK.

PMID- 9572299
TI  - Modulation of the N-methyl-D-aspartate receptor by haloperidol: NR2B-specific
      interactions.
AB  - The dopaminergic antagonist haloperidol has an eight- to 10-fold higher affinity
      for NMDA receptors containing the NR2B (epsilon2) subunit, showing the same
      subunit specificity as ifenprodil, polyamines, and magnesium. In the present
      study, we have compared the effects of mutations altering polyamine and
      ifenprodil sensitivity on haloperidol sensitivity of NMDA receptors. As seen for
      spermidine stimulation, high-affinity haloperidol inhibition is governed by the
      region around amino acid 198, based on results from chimeric murine NR2A/NR2B
      (epislon1/epsilon2) receptors. Mutation of epsilon2E201 in this region to
      asparagine or arginine causes a 10-fold decrease in the ability of haloperidol to
      inhibit 125I-MK-801 binding. Epsilon2E201 does not govern the interactions of
      ifenprodil, because all of the mutants at epsilon2E201 exhibited wild-type
      affinity for ifenprodil. Mutation of epsilon2R337 causes a 400-fold loss in
      apparent affinity for ifenprodil but does not change the effects of haloperidol.
      The structural determinants of spermidine stimulation do not perfectly match
      those for haloperidol inhibition, as mutations of E200 remove haloperidol
      inhibition but do not alter polyamine stimulation. The present results thus
      demonstrate that although spermidine, haloperidol, and ifenprodil share subunit
      selectivity and overlapping pharmacology, they also have specific structural
      determinants.

PMID- 9572301
TI  - Activation of microtubule-associated protein kinase (Erk) and p70 S6 kinase by D2
      dopamine receptors.
AB  - The ability of human and rat D2(short) and D2(long) dopamine receptors to
      activate microtubule-associated protein (MAP) kinase (Erk1/2) and p70 S6 kinase
      has been investigated in recombinant cells expressing these receptors. In cells
      expressing the D2(short) receptor, dopamine activated both enzymes in a transient
      manner but with very different time courses, with activation of Erk being much
      quicker. Activation of both enzymes by dopamine was dose-dependent and could be
      prevented by a range of selective dopamine antagonists. Excellent correlations
      were observed between the potencies of the antagonists for blocking enzyme
      activation and their affinities for the D2 dopamine receptor. Activation of Erk
      and of p70 S6 kinase via the D2 dopamine receptors was prevented by pretreatment
      of the cells with pertussis toxin, indicating the involvement of G proteins of
      the Gi or Go family. Inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase)
      were found to block substantially, but not completely, activation of p70 S6
      kinase by dopamine, suggesting the involvement of PI 3-kinase-dependent and 
      independent signalling pathways in its control by dopamine. p70 S6 kinase
      activation was completely blocked by rapamycin. In the case of Erk, activation
      was partially blocked by wortmannin or LY294002, indicating a possible link with
      PI 3-kinase.

PMID- 9572302
TI  - In vitro binding properties in rat brain of [3H]Ro 25-6981, a potent and
      selective antagonist of NMDA receptors containing NR2B subunits.
AB  - The in vitro binding of a new subtype-selective NMDA receptor antagonist, [3H]Ro
      25-6981, to rat brain membranes and sections was characterized. The compound
      bound to a single site on the membranes with a K(D) of 3 nM and a Bmax of 1.6
      pmol/mg of protein. Specific binding, defined with a new NR2B-specific
      antagonist, Ro 04-5595 [1-(4-chlorophenyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4
      tetrahydroisoqu inoline], at 10 microM, was fully inhibited by several compounds
      with the following rank order of affinities--Ro 25-6981 > CP-101,606 > Ro 04-5595
      = ifenprodil >> eliprodil > haloperidol > spermine > spermidine > MgCl2 > CaCl2-
      and partially inhibited by competitive glutamate recognition site antagonists. A
      high density of binding sites was detected, radioautographically, in several
      layers of the cerebral cortex, in the hippocampus, dentate gyrus, tuberculum
      olfactorium, caudate putamen, medium densities in the globus pallidus, thalamus,
      spinal cord dorsal horn, and motoneurons, whereas the cerebellum, pons, and
      medulla were, with a few exceptions, e.g., locus coeruleus, poorly labeled.
      Overall, the distribution of [3H]Ro 25-6981 binding sites correlated well with
      that of NR2B (but not NR2A) transcripts, revealed by in situ hybridization
      histochemistry. The high affinity of [3H]Ro 25-6981 for NR2B-containing receptors
      renders this compound the ligand of choice to study the regulation of NR2B
      containing receptor expression.

PMID- 9572303
TI  - Histochemical detection of quinone reductase activity in situ using LY 83583
      reduction and oxidation.
AB  - The application of enzymatic staining techniques, using tetrazolium dyes, to
      aldehyde-treated brain sections has revealed the presence of NADPH-diaphorase
      activity attributed to nitric oxide synthase. When evaluating the specificity of
      the putative guanylyl cyclase inhibitor LY 83583, a robust and novel staining
      pattern was noted in epithelial, endothelial, and astrocytic cells when LY 83583
      was included in the NADPH-diaphorase histochemical reaction. This LY 83583
      dependent staining could be blocked by the NAD(P)H:quinone oxidoreductase
      inhibitor dicumarol. Based on its quinone structure, we hypothesized that LY
      83583 was a substrate for the enzyme NAD(P)H:quinone oxidoreductase. Transfection
      of human embryonic kidney 293 cells with the rat liver isoform of NAD(P)H:quinone
      oxidoreductase resulted in robust NADPH- and LY 83583-dependent staining that was
      completely blocked by dicumarol and was not observed in untransfected cells.
      Analysis of transfected cell extracts and brain homogenates indicated that LY
      83583 was a substrate for NAD(P) H:quinone oxidoreductase, with a Km similar to
      the well-characterized substrate menadione. Sensitivity of the nitroblue
      tetrazolium reduction to superoxide dismutase indicated that the reduction of LY
      83583 by NAD(P)H:quinone oxidoreductase leads to superoxide generation. The
      localization of NAD(P)H:quinone oxidoreductase activity to astrocytic cells
      suggests a role for glia in combating oxidative insults to brain and in
      activating quinone-like drugs such as LY 83583.

PMID- 9572304
TI  - Involvement of pituitary adenylate cyclase-activating polypeptide II vasoactive
      intestinal peptide 2 receptor in mouse neocortical astrocytogenesis.
AB  - At the end of neuronal migration, the neopallial germinative zone produces glial
      cells destined to colonize the upper layers of neocortex. High densities of
      binding sites for vasoactive intestinal peptide (VIP) have been found in the
      rodent germinative zone just after completion of neuronal migration, suggesting a
      possible role of VIP in neocortical astrocytogenesis. In the present study,
      administration of a VIP antagonist at embryonic days 17 and 18 to pregnant mice
      was followed by a dramatic depletion of astrocytes in the upper cortical layer of
      the offspring. The depletion of astrocytes was dose-dependent, with a 42%
      reduction in the density of astrocytes observed with 50 microg of antagonist. The
      antagonist effect was reversed by cotreatment with VIP or pituitary adenylate
      cyclase-activating polypeptide (PACAP), suggesting the involvement of a receptor
      common to these two neuropeptides. VIP antagonist-induced inhibition of
      astrocytogenesis was also blocked by Ro 25-1553, a long-acting cyclic VIP
      analogue selective for the PACAP II VIP2 receptor subclass. Our results
      demonstrate that VIP and/or PACAP play a crucial physiological role in
      neocortical astrocytogenesis, possibly through interaction with PACAP II VIP2
      receptors.

PMID- 9572305
TI  - Dorsal root ganglia-specific expression of the beta-galactoside alpha1,2
      fucosyltransferase genes in rabbits.
AB  - The neurons of dorsal root ganglia (DRG) mediate several sensation modalities.
      The carbohydrate antigens on DRG neurons differ with the sensation modalities
      that subsets of neurons convey. Despite the important roles of gangliosides and
      glycoproteins in neuronal differentiation and neuritogenesis of the mammalian
      nervous system, little is known about the mechanisms underlying the regulation of
      glycosylation. We previously demonstrated the expression of H-blood type antigens
      (Fuc alpha1, 2Gal beta) on rabbit DRG neurons of small diameter and dramatic
      changes in H antigens during the perinatal period. To investigate the possible
      biological roles and regulatory mechanisms of H antigens, we recently cloned
      three types of rabbit alpha1,2-fucosyltransferase gene that catalyze the
      biosynthesis of H antigens. Here, we analyze the expression of these genes, RFT
      I, II, and III, in rabbit DRG. The H-type alpha1,2-fucosyltransferase gene, RFT
      I, was expressed in DRG in late embryos to adult rabbits, as detected on northern
      blotting. The other two secretor-type alpha1,2-fucosyltransferase genes, RFT-II
      and III, were observed to be expressed in late embryonic DRG on RT-PCR analysis
      but were not detectable on northern blotting. The expression of the H-type
      alpha1,2-fucosyltransferase gene was analyzed by in situ hybridization and was
      found to be abundant in small-diameter DRG neurons. These results indicate that
      the H-type alpha1,2-fucosyltransferase gene plays a major role in the regulation
      of the H antigen expression in DRG during the perinatal period.

PMID- 9572306
TI  - Amyloid beta-peptide inhibits high-affinity choline uptake and acetylcholine
      release in rat hippocampal slices.
AB  - The characteristic pathological features of the postmortem brain of Alzheimer's
      disease (AD) patients include, among other features, the presence of neuritic
      plaques composed of amyloid beta-peptide (A beta) and the loss of basal forebrain
      cholinergic neurons, which innervate the hippocampus and the cortex. Studies of
      the pathological changes that characterize AD and several other lines of evidence
      indicate that A beta accumulation in vivo may initiate and/or contribute to the
      process of neurodegeneration and thereby the development of AD. However, the
      mechanisms by which A beta peptide influences/causes degeneration of the basal
      forebrain cholinergic neurons and/or the cognitive impairment characteristic of
      AD remain obscure. Using in vitro slice preparations, we have recently reported
      that A beta-related peptides, under acute conditions, potently inhibit K+-evoked
      endogenous acetylcholine (ACh) release from hippocampus and cortex but not from
      striatum. In the present study, we have further characterized A beta-mediated
      inhibition of ACh release and also measured the effects of these peptides on
      choline acetyltransferase (ChAT) activity and high-affinity choline uptake (HACU)
      in hippocampal, cortical, and striatal regions of the rat brain. A beta(1-40)
      (10(-8) M) potently inhibited veratridine-evoked endogenous ACh release from rat
      hippocampal slices and also decreased the K+-evoked release potentiated by the
      nitric oxide-generating agent, sodium nitroprusside (SNP). It is interesting that
      the endogenous cyclic GMP level induced by SNP was found to be unaltered in the
      presence of A beta(1-40). The activity of the enzyme ChAT was not altered by A
      beta peptides in hippocampus, cortex, or striatum. HACU was reduced significantly
      by various A beta peptides (10(-14) to 10(-6) M) in hippocampal and cortical
      synaptosomes. However, the uptake of choline by striatal synaptosomes was altered
      only at high concentration of A beta (10(-6) M). Taken together, these results
      indicate that A beta peptides, under acute conditions, can decrease endogenous
      ACh release and the uptake of choline but exhibit no effect on ChAT activity. In
      addition, the evidence that A beta peptides target primarily the hippocampus and
      cortex provides a potential mechanistic framework suggesting that the
      preferential vulnerability of basal forebrain cholinergic neurons and their
      projections in AD could relate, at least in part, to their sensitivity to A beta
      peptides.

PMID- 9572307
TI  - Structural requirements for ligand interactions at the benzodiazepine recognition
      site of the GABA(A) receptor.
AB  - His101 of the GABA(A) receptor alpha1 subunit is an important determinant of
      benzodiazepine recognition and a major site of photolabeling by
      [3H]flunitrazepam. To investigate further the chemical specificity of the residue
      in this position, we substituted it with phenylalanine, tyrosine, lysine,
      glutamate, glutamine, or cysteine. The mutant alpha subunits were coexpressed
      with the rat beta2 and gamma2 subunits in TSA201 cells, and the effects of the
      substitutions on the binding of benzodiazepine site ligands were examined. [3H]Ro
      15-4513 bound to all mutant receptors with equal or greater affinity than to the
      wild-type receptor. However, flunitrazepam and ZK93423 recognition was adversely
      affected by substitutions of the amino acid in this position. The binding of the
      antagonists, Ro 15-1788 and ZK93426, was also sensitive to the mutations, with
      the largest decreases in affinity occurring with the tyrosine, lysine, and
      glutamate substitutions. In all mutants that recognized flunitrazepam, GABA
      potentiated the binding of this ligand to a similar extent, suggesting that it is
      a full agonist at these receptors. The effects of GABA on the binding of Ro 15
      1788 and Ro 15-4513 suggest that their efficacies may have been changed by some
      of the substitutions. This study further emphasizes the importance of the residue
      at position 101 in both ligand recognition and pharmacological effect.

PMID- 9572308
TI  - Peroxynitrite and brain mitochondria: evidence for increased proton leak.
AB  - Peroxynitrite has been reported to inhibit irreversibly mitochondrial
      respiration. Here we show that three sequential additions of 200 microM
      peroxynitrite (initial concentration) to rat brain mitochondria (0.2 mg of
      protein/ml) significantly stimulated state 4 respiration and that further
      additions progressively inhibited it. No stimulation of state 3 respiration or of
      the maximal enzymatic activities of the respiratory chain complexes was observed
      on identical peroxynitrite exposure. State 4 respiration is a consequence of the
      proton permeability of the mitochondrial inner membrane, and we demonstrate that
      the peroxynitrite-induced stimulation of state 4 respiration is accompanied by a
      decreased mitochondrial membrane potential, suggesting an increase in this proton
      leak. Cyclosporin A did not affect the stimulation, suggesting no involvement of
      the mitochondrial permeability transition pore. The stimulation was prevented by
      the lipid-soluble vitamin E analogue Trolox, suggesting the involvement of lipid
      peroxidation, a proposed mechanism of peroxynitrite cytotoxicity. Lipid
      peroxidation has previously been reported to increase membrane bilayer proton
      permeability. The high polyunsaturate content of brain mitochondrial
      phospholipids may predispose them to peroxidation, and thus a peroxynitrite
      induced, lipid peroxidation-mediated increase in proton leak may apply
      particularly to brain mitochondria and to certain neurodegenerative disorders
      thought to proceed via mechanisms of mitochondrial oxidative damage.

PMID- 9572309
TI  - Differential coupling of mu-, delta-, and kappa-opioid receptors to G alpha16
      mediated stimulation of phospholipase C.
AB  - The mu-opioid receptor has recently been shown to stimulate phosphoinositide
      specific phospholipase C via the pertussis toxin-sensitive G16 protein. Given the
      promiscuous nature of G16 and the high degree of resemblance of signaling
      properties of the three opioid receptors, both delta- and kappa-opioid receptors
      are likely to activate G16. Interactions of delta- and kappa-opioid receptors
      with G16 were examined by coexpressing the opioid receptors and G alpha16 in COS
      7 cells. The delta-selective agonist [D-Pen2,D-Pen5] enkephalin potently
      stimulated the formation of inositol phosphates in cells coexpressing the delta
      opioid receptor and G alpha16. The delta-opioid receptor-mediated stimulation of
      phospholipase C was absolutely dependent on the coexpression of G alpha16 and
      exhibited appropriate ligand selectivity and dose dependency. Similar
      transfection studies revealed only weak stimulation by the mu-opioid receptor,
      whereas the kappa-opioid receptor produced moderate phospholipase C activity. G
      alpha16 thus appeared to interact differentially with the three opioid receptors.
      Radioligand binding assays indicate that the mu-opioid receptor was expressed at
      a lower level than those of the delta- and kappa-opioid receptors. To examine if
      differential coupling to G alpha16 is prevalent, a panel of Gs- or Gi-coupled
      receptors was coexpressed with G alpha16 in COS-7 cells and assayed for agonist
      induced stimulation of phospholipase C. Activation of alpha2- and beta2
      adrenergic, dopamine D1 and D2, adenosine A1, somatostatin-1 and -2, C5a, formyl
      peptide, and luteinizing hormone receptors all resulted in stimulation of
      phospholipase C, with maximal stimulations ranging from 1.5- to almost 17-fold.
      These findings suggest that the promiscuous G alpha16 can in fact discriminate
      among different receptors and that such preferential interaction might in part be
      due to the abundance of receptors.

PMID- 9572311
TI  - Regulators of G protein signaling: rapid changes in mRNA abundance in response to
      amphetamine.
AB  - This study examined mRNAs encoding regulators of G protein signaling (RGSs)
      expressed within the striatum and determined whether their expression in the
      caudate putamen was altered by amphetamine. RT-PCR techniques were used to clone
      cDNA probes of RGSs expressed within the rat striatum. Northern blot analysis of
      caudate putamen and nucleus accumbens RNA determined the relative abundance of
      RGS mRNA expressed within the caudate putamen and adjacent nucleus accumbens to
      be RGS 2 > RGS 5 > RGS 16 > RGS 4 = RGS 9 > RGS 8 = RGS 3. A single injection of
      amphetamine rapidly and transiently induced RGS 2 mRNA. The temporal pattern of
      induction of RGS 2 strongly resembled that of the immediate early gene c-fos.
      Levels of mRNAs of RGS 3 and 5 steadily increased over a 4-h interval, as did
      that of the 6.6-kb transcript of RGS 8. The level of RGS 9 mRNA, which shows
      strong striatal-specific expression, steadily decreased over a 4-h interval,
      whereas RGS 4 and 16 and the 3.9-kb transcript of RGS 8 were not significantly
      affected at any point examined. The ability of amphetamine to alter RGS mRNA
      expression within the caudate putamen suggests these proteins may play an
      important role in adaptive processes to psychostimulant exposure.

PMID- 9572310
TI  - Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative
      stress.
AB  - Increased awareness for a role of oxidative stress in the pathogenesis of
      Alzheimer's disease has highlighted the issue of whether oxidative damage is a
      fundamental step in the pathogenesis or instead results from disease-associated
      pathology. In vitro experiments support both possibilities: Oxidative stress
      increases amyloid-beta production, and, conversely, amyloid-beta increases
      oxidative damage. To address the relationship between amyloid-beta and oxidative
      stress in vivo, we examined, using an array of oxidative markers, transgenic mice
      that overexpress amyloid-beta precursor protein and, as in Alzheimer's disease,
      develop characteristic amyloid-beta deposits within the brain parenchyma.
      Transgenic animals show the same type of oxidative damage that is found in
      Alzheimer's disease, and it is important that this damage directly correlates
      with the presence of amyloid-beta deposits. The significance of these studies is
      twofold. First, they provide evidence that amyloid-beta and oxidative damage are
      inextricably linked in vivo. Second, they support the use of transgenic animals
      for the development of antioxidant therapeutic strategies.

PMID- 9572312
TI  - Artefacts in HPLC detection of 3-nitrotyrosine in human brain tissue.
AB  - An HPLC method was used for quantification of 3-nitrotyrosine (3-NT) in human
      postmortem brain tissue. A peak with similar retention time to 3-NT was detected
      in brain tissue from patients with Parkinson's disease, Huntington's chorea,
      multiple system atrophy, and Alzheimer's disease but not in control tissue. The
      peak was lost on reduction with dithionite, a criterion often used to identify 3
      NT. Tissue from the same neurodegenerative diseases was analysed by HPLC using a
      photodiode array detector in series with an amperometric electrochemical
      detector, but the peak was found not to be 3-NT. The absorbance spectrum,
      fragmentation pattern on mass spectroscopy, and electrochemical profile of this
      peak do not match authentic 3-NT. A search of the mass spectroscopy databases
      failed to reveal its identity. The presence of this closely eluting, dithionite
      reducible peak could confound analysis of human tissues for 3-NT. In vitro
      experiments showed that high concentrations of peroxynitrite were needed to
      achieve detectable levels of 3-NT in human brain tissue.

PMID- 9572313
TI  - Evolving strategies for managing nonsteroidal anti-inflammatory drug-associated
      ulcers: chairmen's introduction.

PMID- 9572315
TI  - Use and benefits of nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) continue to be used very widely in
      the community. Their use reflects the significant burden of rheumatic disease on
      the general population, and they form a basis for the treatment of inflammation
      in and around the joint. Furthermore, NSAIDs are also being used increasingly for
      nonrheumatic conditions, including acute and chronic pain, biliary and ureteric
      colic, and dysmenorrhea. Recent studies in osteoarthritis have suggested that a
      significant number of patients previously maintained on NSAIDs can be equally
      well treated using analgesic agents, such as paracetamol. In noninflammatory
      rheumatic diseases, analgesics and physical therapies should be the initial
      treatment of choice and, even in inflammatory rheumatic diseases, NSAID use may
      be reduced by the addition of pure analgesics to the treatment regimen. A large
      number of NSAIDs now exist, and there is variability in clinical response to
      NSAIDs among individual patients. Concern over the widespread use of NSAIDs is
      largely related to their side-effects. These include adverse reactions in the
      gastrointestinal tract, kidney, liver, dermis, and central nervous system, as
      well as hematologic problems. The potential for drug interactions with NSAIDs is
      also large, as they are often administered to a population with significant co
      morbidities. NSAIDs play a major role in the management of acute and chronic
      rheumatic diseases, but their use needs to be tempered with the realization that
      they can cause potentially serious adverse reactions. These side-effects can be
      reduced by careful attention to the dose and duration of therapy, concomitant
      risk factors, and the combined use of more specific drugs to reduce disease
      activity. Furthermore, the gastrointestinal side-effects of NSAIDs may be treated
      and prevented by using appropriate therapy in combination with NSAIDs.

PMID- 9572314
TI  - Mechanism of action of nonsteroidal anti-inflammatory drugs.
AB  - Salicylic acid and salicylates, obtained from natural sources, have long been
      used as medicaments. Salicylic acid was chemically synthesized in 1860 and was
      used as an antiseptic, an antipyretic, and an antirheumatic. Almost 40 years
      later, aspirin was developed as a more palatable form of salicylate. Soon after,
      other drugs having similar actions to aspirin were discovered, and the group was
      termed the "aspirin-like drugs" (also now termed the nonsteroidal anti
      inflammatory drugs [NSAIDs]). Twenty-five years ago, it was proposed that the
      mechanism of action of NSAIDs was through their inhibition of prostaglandin
      biosynthesis. Since then, there has been general acceptance of the concept that
      these drugs work by inhibition of the enzyme cyclo-oxygenase (COX), which we now
      know to have at least two distinct isoforms: the constitutive isoform, COX-1, and
      the inducible isoform, COX-2. COX-1 has clear physiologic functions. Its
      activation leads, for instance, to the production of prostacyclin, which when
      released by the endothelium is antithrombogenic and when released by the gastric
      mucosa is cytoprotective. COX-2, discovered 6 years ago, is induced by
      inflammatory stimuli and cytokines in migratory and other cells. It is therefore
      attractive to suggest that the anti-inflammatory actions of NSAIDs are due to
      inhibition of COX-2, whereas the unwanted side-effects, such as irritation of the
      stomach lining, are due to inhibition of COX-1. Drugs that have the highest COX-2
      activity and a more favorable COX-2: COX-1 activity ratio will have a potent anti
      inflammatory activity with fewer side-effects than drugs with a less favorable
      COX-2: COX-1 activity ratio. The identification of selective inhibitors of COX-2
      will therefore lead to advances in therapy.

PMID- 9572316
TI  - Quality-of-life considerations with respect to arthritis and nonsteroidal anti
      inflammatory drugs.
AB  - This article first presents a hierarchical general quality-of-life framework,
      beginning with global "outcome" and progressing through dimensions,
      subdimensions, components, and finally to specific variables. Second, the Health
      Assessment Questionnaire (HAQ) is described as an example of a set of instruments
      designed to assess such a framework. A simple visual analog scale, which was
      incorporated into the HAQ in 1980 and which ranks the status of health from "very
      poor" to "very well," has been shown to correlate strongly with traditional
      quality-of-life instruments, such as the Torrance "Feeling Thermometer." Finally,
      the requirement for a side-effect index to assess quality of life related to
      different drug therapies is discussed. Comparative drug adverse event profiles
      are highlighted, a side-effect index presented, and some preliminary results and
      conclusions outlined. With drugs used for the treatment of rheumatic diseases,
      adverse events have been shown to vary widely. Indeed, the differences in side
      effects are often 2-3-fold between drugs of the same class. Furthermore, the
      incidence of adverse events related to the use of many nonsteroidal anti
      inflammatory drugs has been shown to be greater than that seen with a number of
      disease-modifying antirheumatic drugs.

PMID- 9572317
TI  - Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal
      injury.
AB  - Nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most
      frequently used drugs in many countries. Use of the majority of NSAIDs increases
      with age, primarily for symptoms associated with osteoarthritis and other chronic
      musculoskeletal conditions. Population-based studies have shown that, on any
      given day, 10-20% of elderly people (> or = 65 years old) have a current or
      recent NSAID prescription. Over a 6-month period in Alberta, Canada, 27% of
      elderly people were prescribed NSAIDs. Furthermore, in Tennessee (USA), 40% of
      elderly people received at least one NSAID prescription annually, and 6% had
      NSAID prescriptions for > 75% of the year. NSAIDs cause a wide variety of side
      effects. The most clinically important side-effects are upper gastrointestinal
      tract dyspepsia, peptic ulceration, hemorrhage, and perforation, leading to death
      in some patients. Gastrointestinal side-effects are common; the most common NSAID
      associated side-effect is epigastric pain/indigestion. Gastrointestinal side
      effects are also a frequent reason both for withdrawal of NSAIDs and for co
      treatment with another drug. Indeed, in two population-based studies of people
      aged > or = 65 years, the use of agents to prevent peptic ulcers or relieve
      dyspepsia was nearly twice as common in regular NSAID users (20-26%) than in non
      NSAID users (11%). In Alberta, Canada, it has been estimated that NSAID use
      accounts for 28% of all prescriptions for anti-ulcer drugs in people aged at
      least 65 years. Many studies have now shown that NSAIDs increase the risk of
      peptic ulcer complications by 3-5-fold, and in several different populations it
      has been estimated that 15-35% of all peptic ulcer complications are due to
      NSAIDs. In the United States alone, there are an estimated 41,000
      hospitalizations and 3,300 deaths each year among the elderly that are associated
      with NSAIDs. Factors that increase the risk of serious peptic ulcer disease
      include older age, history of peptic ulcer disease, gastrointestinal hemorrhage,
      dyspepsia, and/or previous NSAID intolerance, as well as several measures of poor
      health.

PMID- 9572318
TI  - Variability in risk of gastrointestinal complications with different nonsteroidal
      anti-inflammatory drugs.
AB  - Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) is known to increase
      substantially the risk of upper gastrointestinal bleeding and/or perforation. A
      meta-analysis of the available epidemiologic studies has shown that there are
      wide differences between individual drugs in the risk of inducing
      gastrointestinal complications. Of the NSAIDs in common use, ibuprofen and
      diclofenac were found to be associated with the lowest relative risk;
      indomethacin, naproxen, sulindac, and aspirin were associated with intermediate
      risk; and azapropazone, tolmetin, ketoprofen, and piroxicam were associated with
      higher risk. Some of these apparent differences in toxicity may, however, be dose
      related. The low risk of gastrointestinal complications associated with ibuprofen
      appears to be attributable to the low doses that are prescribed routinely in
      clinical practice. Higher doses of ibuprofen were associated with relative risks
      similar to those of naproxen and indomethacin. Thus, as first-line treatment,
      patients should be prescribed the lowest effective dose of an NSAID that appears
      to be associated with a comparatively low risk. This should substantially reduce
      the morbidity and mortality from serious gastrointestinal complications that are
      associated with the use of these drugs.

PMID- 9572319
TI  - Does Helicobacter pylori status affect nonsteroidal anti-inflammatory drug
      associated gastroduodenal pathology?
AB  - There are two lines of thought regarding the interrelationship between the
      damaging effects of Helicobacter pylori and those of nonsteroidal anti
      inflammatory drugs (NSAIDs) on the gastroduodenal mucosa. First, both pathogenic
      factors exert a damaging effect on the mucosa, and therefore an additive, or even
      synergistic, effect occurs, leading to aggravation of mucosal damage. Second,
      mutual antagonism exists, leading to one of the pathogenic factors actually
      deriving some protection from the damaging potential of the other.
      Microscopically, H. pylori- and NSAID-associated gastritis are recognized as two
      separate entities. Furthermore, pathologically, the mechanisms of mucosal damage
      of the two factors have important differences; for example, H. pylori increases
      the synthesis of prostaglandins, whereas NSAIDs inhibit prostaglandin synthesis.
      The role of H. pylori infection in patients with NSAID-associated peptic ulcers
      has been addressed recently in two large, randomized, multicenter trials. From
      these studies, it appears that antisecretory drugs are more effective in H.
      pylori-positive peptic ulcer patients taking NSAIDs than in H. pylori-negative
      patients taking these drugs. The studies, however, do not provide any evidence
      that H. pylori infection reduces the pathogenic effects of NSAIDs. Other studies,
      however, have shown protection against NSAID-associated gastroduodenal damage in
      H. pylori-negative patients. Thus, there are no firm conclusions on the role of
      H. pylori infection in patients with NSAID-associated peptic ulcers. Based on the
      available data, however, practical considerations and guidelines are listed.

PMID- 9572320
TI  - Mechanisms of ulcer healing and effects of nonsteroidal anti-inflammatory drugs.
AB  - Ulceration of the gastroduodenal mucosa occurs frequently in humans, particularly
      in patients with a history of peptic ulcer disease. In order for healing to
      occur, mucosal damage stimulates secretion of growth factors in the adjacent
      mucosa and ulcer bed. Peptic ulcer healing is accomplished by the filling of the
      mucosal defect with cells that migrate from the ulcer margin and by connective
      tissue, including microvessels originating from granulation tissue. Peptic ulcer
      healing is accelerated both in humans and experimental models by gastric acid
      inhibition, which enhances cell migration and maturation of the granulation
      tissue. In experimental models, peptic ulcer healing can also be accelerated by
      oral administration of basic fibroblast growth factor, which increases
      angiogenesis in the ulcer bed, or by nitric oxide-releasing compounds, which
      improve gastric blood flow. Clinical and experimental data indicate that
      traditional nonsteroidal anti-inflammatory drugs (NSAIDs) delay the healing of
      peptic ulcers by interfering with the action of growth factors, decreasing
      epithelial cell proliferation in the ulcer margin, decreasing angiogenesis in the
      ulcer bed, and slowing maturation of the granulation tissue. In order to reduce
      the gastroduodenal side-effects of NSAIDs, selective cyclo-oxygenase (COX)-2
      inhibitors have been developed, which inhibit the inducible COX-2 isoform in
      inflammatory tissue but have only limited effect on the constitutive COX-1
      isoform in the stomach. It has been reported that the selective COX-2 inhibitor L
      745,337 has a reduced liability for gastrointestinal ulceration. In our chronic
      experimental gastric ulcer model in rats, however, delay of gastric ulcer healing
      with L-745,337 was comparable to that with ordinary NSAIDs. It has also been
      reported that nitric oxide-releasing NSAIDs have a low relative risk of
      gastrointestinal ulceration but, again, in our chronic gastric ulcer model,
      nitric oxide did not reverse NSAID-induced deleterious effects on ulcer healing.
      In contrast, the proton pump inhibitor omeprazole has been shown to reverse NSAID
      induced deleterious effects on gastric ulcer healing in our model. Comparable
      results have also been reported in humans. Histologic analysis has shown that
      omeprazole reverses the effects of NSAIDs on cell proliferation, angiogenesis,
      and maturation of the granulation tissue. In conclusion, only highly effective
      gastric acid inhibition reliably reverses NSAID-induced delay of gastric ulcer
      healing.

PMID- 9572321
TI  - Why proton pump inhibition should heal and protect against nonsteroidal anti
      inflammatory drug ulcers.
AB  - Several lines of evidence provide support for the potential of gastric acid
      inhibitory therapy in the management of nonsteroidal anti-inflammatory drug
      (NSAID)-associated gastroduodenal injury. Studies on the rat stomach have shown
      that the acute mucosal injury produced by both aspirin and indomethacin can be
      prevented by elevation of the pH of the gastric contents of >4.0. The pH
      dependent pattern of mucosal injury is best explained by the very low activity of
      gastric pepsin above pH 4.0. This view is supported by studies of experimental
      esophagitis, which indicate that the pH-activity curve of gastric pepsin
      approximates the aggressiveness of acid-pepsin mixtures to the esophageal mucosa.
      Healthy human volunteer studies have shown that elevation of intragastric pH with
      omeprazole greatly reduces, or abolishes, aspirin-associated gastric
      microbleeding. A small amount of clinical data also support the view that
      elevation of gastric pH with acid-inhibitory therapy is a promising option for
      both the treatment of established NSAID-associated chronic peptic ulcer, even
      during continued NSAID use, and for prophylaxis against the develop of chronic
      gastric and duodenal ulcers during NSAID therapy. These data indicate
      consistently that the benefits from gastric acid-inhibitory therapy are
      proportional to the degree of elevation of gastric pH by therapy. This dose
      response relationship suggests that proton pump inhibition has the potential to
      achieve superior results in patients who have, or who are at risk of, NSAID
      associated peptic ulcer, when compared with agents that inhibit gastric acid
      secretion to lower levels than seen with proton pump inhibition.

PMID- 9572322
TI  - New data on healing of nonsteroidal anti-inflammatory drug-associated ulcers and
      erosions. Omeprazole NSAID Steering Committee.
AB  - A total of 1,456 patients were available for the All Patients Treated analysis of
      two large, randomized, double-blind, multicenter, controlled studies (Acid
      Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer
      Treatment [ASTRONAUT] and Omeprazole versus Misoprostol for NSAID-Induced Ulcer
      Management [OMNIUM]). These studies examined the efficacies of omeprazole, 20 and
      40 mg once daily (both studies), ranitidine, 150 mg twice daily (ASTRONAUT), and
      misoprostol, 200 microg four times daily (OMNIUM), for the healing of gastric
      ulcer, duodenal ulcer, or erosions, and the relief of dyspeptic symptoms. At
      entry, patients were receiving, and continued to receive, nonsteroidal anti
      inflammatory drugs (NSAIDs), and had a gastric or duodenal ulcer, and/or >10
      erosions in the stomach or duodenum at initial endoscopy. Patients were
      randomized to blinded treatment for 4/8 weeks until treatment success, which was
      defined as the healing of ulcer(s), <5 erosions at any site, and not more than
      mild dyspeptic symptoms. The proportions of patients reaching treatment success
      by 8 weeks were 77% with both doses of omeprazole, 63% with ranitidine, and 71%
      with misoprostol. In patients who initially had a gastric ulcer, more ulcers were
      healed at 8 weeks with omeprazole, 20 (83%) and 40 mg once daily (82%), than with
      ranitidine (64%) or misoprostol (74%). In patients who initially had a duodenal
      ulcer, 93% were healed at 8 weeks with omeprazole, 20 mg once daily, compared
      with 88% for omeprazole, 40 mg once daily, 79% for ranitidine, and 79% for
      misoprostol. Erosions healed slightly faster at 4 weeks with misoprostol,
      compared with the other regimens, but by 8 weeks most patients had <5 erosions
      per gastroduodenal region in each treatment group. Diarrhea and abdominal pain
      were more common in patients taking misoprostol, as were adverse events leading
      to withdrawal. Patients with duodenal ulcer or erosions at entry and the presence
      of Helicobacter pylori were good prognostic factors for overall treatment
      success. Using a model that included only patients with ulcers, those with
      smaller ulcers also had a higher likelihood of achieving treatment success.
      Against the background of these new data, omeprazole is the treatment of choice
      for healing NSAID-associated ulcers, on the basis of its efficacy and
      tolerability, and the optimal dose appears to be 20 mg once daily.

PMID- 9572323
TI  - Healing of nonsteroidal anti-inflammatory drug-associated ulcers and erosions,
      and relief of dyspeptic symptoms: a commentary on the new data.

PMID- 9572324
TI  - Progress in prophylaxis against nonsteroidal anti-inflammatory drug-associated
      ulcers and erosions. Omeprazole NSAID Steering Committee.
AB  - Four large clinical studies have shown that omeprazole, 20 mg once daily, is
      effective in preventing the significant gastroduodenal consequences of
      nonsteroidal anti-inflammatory drugs (NSAIDs). In the Scandinavian Collaborative
      Ulcer Recurrence (SCUR) study, patients were randomized (without initial
      endoscopy) to receive omeprazole or placebo for up to 3 months. Of the patients
      treated with omeprazole, 24.7% experienced treatment failure, compared with 50.0%
      of those on placebo. Fewer patients in the omeprazole group than in the placebo
      group developed a peptic ulcer (4.7% versus 16.7%, respectively) or dyspeptic
      symptoms (8.2% versus 20.0%, respectively). In the Omeprazole versus Placebo as
      Prophylaxis of Ulcers and Erosions from NSAID Treatment (OPPULENT) study,
      patients were also randomized to receive omeprazole or placebo. The estimated
      probability of remaining in remission for 6 months while receiving omeprazole was
      0.78, compared with 0.53 for placebo. Fourteen (16.5%) patients on placebo
      developed peptic ulcer(s), compared with three (3.6%) patients on omeprazole. The
      Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management (OMNIUM) study
      consisted of a healing and a prophylactic phase. Patients who successfully
      completed the healing phase were re-randomized to receive omeprazole,
      misoprostol, or placebo for up to 6 months. In patients receiving omeprazole,
      36.5% experienced treatment failure, compared with 48.6% of those on misoprostol,
      and 67.7% of those on placebo. Omeprazole and misoprostol appeared to be equally
      effective in preventing gastric ulcer; by contrast, omeprazole was highly
      effective in preventing duodenal ulcer, when compared with misoprostol and
      placebo. The Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID
      Associated Ulcer Treatment (ASTRONAUT) study also consisted of a healing and a
      prophylactic phase. Patients who successfully completed the healing phase were re
      randomized to receive omeprazole or ranitidine for up to 6 months. In patients
      receiving omeprazole, 26.2% experienced treatment failure, compared with 37.7% of
      those on ranitidine. The percentages of patients with a peptic ulcer relapse were
      5.7% for omeprazole and 19.5% for ranitidine. The data show that omeprazole is an
      effective and well-tolerated agent for both primary and secondary (maintenance)
      prophylaxis in patients receiving NSAIDs.

PMID- 9572325
TI  - Prophylaxis against nonsteroidal anti-inflammatory drug-associated ulcers and
      erosions: a commentary on the new data.

PMID- 9572326
TI  - Management of nonsteroidal anti-inflammatory drug-associated lesions: a cost
      effectiveness perspective.
AB  - Results are presented from a cost-effectiveness analysis of the acute healing
      phases of two new clinical studies. Acute treatment with omeprazole, 20 mg once
      daily, is compared with misoprostol, 200 microg four times daily, or ranitidine,
      150 mg twice daily, in patients with nonsteroidal anti-inflammatory drug (NSAID)
      associated gastroduodenal lesions (gastric ulcer, duodenal ulcer, and/or >10
      erosions in either the stomach or duodenum). The cost-effectiveness comparisons
      indicate that omeprazole is cost-effective when compared with ranitidine in the
      treatment of gastric ulcers, duodenal ulcers, and erosions only, and that
      omeprazole is cost-effective when compared with misoprostol in the treatment of
      gastric ulcers and duodenal ulcers. In patients with erosions only, misoprostol
      is cost-effective when compared with omeprazole. When assessing the uncertainty
      of these estimates, a definite conclusion can be made in only two comparisons:
      omeprazole is cost-effective when compared with ranitidine in the treatment of
      gastric ulcers, and misoprostol is cost-effective when compared with omeprazole
      in the treatment of erosions only. However, the clinical studies were not powered
      for assessing the cost-effectiveness of the treatment alternatives, which impedes
      the uncertainty assessment. The determinants of the cost-effectiveness of
      prophylactic strategies are also discussed, as well as the need for further
      studies that include relevant outcome measures and a design that reflects actual
      clinical practice.

PMID- 9572327
TI  - Practical management: a keypad-based interactive session.
AB  - If controlled therapeutic, epidemiologic, and pathologic data are to be put
      rationally into clinical practice, they need to be evaluated against real
      clinical scenarios. This was done by presenting the symposium delegates with a
      clinical case and then asking management questions, which were answered using a
      keypad system.

PMID- 9572328
TI  - Evolving strategies for managing nonsteroidal anti-inflammatory drug-associated
      ulcers: chairmen's conclusion.

PMID- 9572329
TI  - Duplex scan surveillance of infra-inguinal bypass grafts.

PMID- 9572330
TI  - Should peri-operative infra-inguinal graft duplex scans be routinely performed?
AB  - BACKGROUND: The ability of duplex ultrasound graft surveillance to detect graft
      stenosis is well documented. However, the optimal time to commence duplex
      ultrasound graft surveillance is not clear. METHODS: An early duplex ultrasound
      study was performed on 90 infra-inguinal bypass grafts within 2 weeks of surgery.
      Further duplex scans were performed at intervals after surgery of 1 month, 3
      months, 6 months, 1 year and then annually. An ankle/brachial systolic pressure
      index (ABI) was performed before the infra-inguinal bypass and then 24 h after
      the surgery. The ABI was also routinely measured at the time of each graft duplex
      examination. RESULTS: Six graft thromboses (6.7%) were demonstrated on the first
      graft duplex within 2 weeks of the surgery. The 24-hour postoperative resting ABI
      were less than 0.5 in all six cases. Significant graft stenoses (> 50%) or native
      artery diseases were detected in six cases (6.7%) on the first graft scan
      (proximal anastomosis stenosis, 1: mid-graft stenosis, 3; peroneal artery
      stenosis, 1; popliteal artery occlusion, 1). The resting ABI was less than 0.5 in
      one of these cases. Vein patch angioplasty was performed on graft stenosis in two
      cases following the first duplex scan. In 78 cases with either normal or minimal
      graft/native artery stenosis (< 50%), the resting ABI were less than 0.5 in only
      two cases (2.6%). The first graft duplex ultrasound examinations were technically
      difficult or gave a poor image in 21 cases (23.3%). During the subsequent graft
      duplex follow-up, seven graft thromboses were demonstrated at an average of 5.9
      months after surgery (1-12 months). Significant stenosis (> 50%) was demonstrated
      in 10 additional cases at an average of 8.5 months after surgery (1-12 months).
      CONCLUSIONS: The data of the present study do not support routine peri-operative
      graft duplex scanning in addition to a 1-month graft duplex scan. Early
      postoperative resting ABI should be routinely performed. If the resting ABI is
      less than 0.5, an immediate duplex scan should be carried out to assess graft
      integrity. A long-term non-invasive graft surveillance programme is important in
      the detection of graft stenosis.

PMID- 9572331
TI  - Management and outcome of popliteal artery aneurysms in a New Zealand provincial
      centre.
AB  - BACKGROUND: The experience of management of popliteal artery aneurysms (PAA) in a
      provincial centre is described. METHODS: Patients were identified from vascular
      audit, and case notes were reviewed retrospectively. RESULTS: There were 17
      patients with 23 PAA over 12 years. All patients were male, with a mean age of 73
      years. Other aneurysms were present in 77% of patients, 59% had bilateral PAA and
      41% had an associated abdominal aortic aneurysm (AAA). Mean follow-up was 3
      years, 3 months (range, 1 month - 7 years). There were 11 acute procedures, and
      12 elective. Reconstruction with bypass and ligation of the aneurysm was
      performed in all elective and 9/11 acute procedures. Of the 21 bypass procedures,
      17 used autologous vein, three used GoreTex, and 1 composite graft. There were
      two PAA that were not reconstructable. All the vein grafts remained patent during
      the time of follow-up, but two of the three GoreTex grafts failed. Successful
      reconstruction was achieved in 11/12 elective and 9/11 acute cases. All grafts in
      the acute group remained patent during the time of follow-up (mean, 3.5 years),
      in the elective group 11/12 grafts (91%) remained patent (mean follow-up, 2.5
      years). CONCLUSIONS: An excellent outcome was achieved in both elective and acute
      procedures. Autologous vein grafts appear to give better results than synthetic
      grafts. Due to the high incidence of multiple aneurysms, screening for other
      aneurysms is suggested.

PMID- 9572332
TI  - Surgical management of diabetic foot complications: the Far North Queensland
      profile.
AB  - BACKGROUND: Foot complications in diabetes incur huge human and medical costs.
      There is a high incidence of complicated diabetes mellitus in Far North
      Queensland, particularly in the indigenous communities. METHODS: An audit of 51
      patients admitted to Cairns Base Hospital from July 1992 to December 1994 with
      diabetic foot complications requiring surgical intervention was performed.
      RESULTS: The majority of surgical procedures were for serious infections in
      neuropathic feet precipitated by minor trauma. Surgical procedures included
      debridement/drainage, minor amputation, major amputation and arterial bypass.
      Half of the patients required more than one procedure and/or multiple admissions.
      Average length of stay was 48 days. Indigenous patients were overrepresented in
      this audited group. CONCLUSIONS: Prevention or minimization of diabetic foot
      complications can be achieved only through improvement in education and vigilance
      at all levels of the treatment process from community to hospital. Special
      attention to the needs of indigenous communities with a high incidence of
      diabetes must be a feature of any future initiatives.

PMID- 9572333
TI  - Penetrating trauma in Auckland: 12 years on.
AB  - BACKGROUND: The current spectrum of penetrating trauma presenting to Auckland
      Hospital is described and whether this differs from the situation in 1983 is
      determined. METHODS: Prospectively collected trauma registry data were used to
      describe the characteristics of penetrating trauma cases presenting to Auckland
      Hospital during the 1995 calendar year. Using data collected from a previous
      study in 1983, comparisons were made of the incidence, severity, and outcome of
      penetrating trauma cases between these two cohorts. RESULTS: In 1995, 96
      patients, representing 7.3% of total trauma admissions, presented to Auckland
      Hospital following penetrating trauma. Of these, 32 patients were admitted by the
      trauma team via the resuscitation room, 13 were admitted to the intensive care
      unit (ICU) and four died. The median age of these patients was 30 years and
      median Injury Severity Score, 4. In comparison with the 1983 patients there was
      no demonstrable change in the numbers of patients or their length of stay.
      Although injury severity was similar in the 1995 cohort, fewer patients were
      admitted to the ICU. Mortality of the 'trauma team' group was 4/32 in 1995
      compared with 7/33 in 1983. CONCLUSIONS: Despite public concerns, the frequency
      of penetrating trauma cases presenting to Auckland Hospital was similar in 1995
      and 1983. There is a non-significant decrease in length of stay and mortality in
      the 1995 cohort.

PMID- 9572334
TI  - Aortic transection.
AB  - BACKGROUND: Traumatic aortic transection is uncommon in those trauma patients
      reaching hospital alive. METHODS: The Victorian Major Trauma Study (VMTS)
      received data from 25 hospitals in Victoria, a State of 4.4 million people, and
      identified 1874 patients with blunt trauma and Injury Severity Score (ISS)
      greater than 15 over a 2-year period (1 March 1992-28 February 1993 and 1 May
      1994-30 April 1995). The Federal Office of Road Safety (FORS) examined coronial
      data from 1 January 1992 to 31 December 1992. These studies allowed a
      retrospective, population-based review of experience with aortic transection.
      RESULTS: The VMTS identified 19 patients who reached hospital, with signs of life
      at the scene of the accident, during a 2-year period. Of these, 8 left hospital
      alive: 4 without disability and 4 with disability related to non-thoracic injury.
      The annual incidence of aortic transection for the State, based on FORS data, was
      13 per 1000000, lower than other reported studies. Review of the management of
      patients in hospital confirmed the usefulness of initial chest X-ray in diagnosis
      and the high incidence of associated injury. CONCLUSIONS: The study raises a
      number of issues, including the question of direct referral of patients with
      severe chest injury to hospitals with cardiothoracic facilities, increased use of
      transoesophageal echocardiography in diagnosis and increased use of immediate
      laparotomy and thoracotomy in certain patients.

PMID- 9572335
TI  - Peritonitis following percutaneous gastrostomy in children: management
      guidelines.
AB  - BACKGROUND: To establish the incidence, timing and outcome of peritonitis
      following percutaneous gastrostomy (PEG) insertion in children. METHODS: Patients
      developing peritonitis after PEG insertion during a 5-year period (1990-95) were
      identified. Variables analysed included clinical presentation, management,
      operative findings and outcome. RESULTS: One hundred and twenty paediatric
      patients received 130 PEG in the 5-year period. Eight children developed
      peritonitis: 4 within 24 h of PEG insertion and 4 following routine PEG tube
      change (3-18 months later). All four patients developing early peritonitis
      underwent laparotomy in whom three had sustained major damage to adjacent
      viscera. The fourth patient had a negative laparotomy, but died from continued
      overwhelming sepsis. All four patients who developed peritonitis after a routine
      tube change underwent a tube contrast study. In two children a gastrocolic
      fistula was identified and surgically repaired. Contrast studies in two patients
      detected an intraperitoneal leak. This problem resolved with conservative
      management in both cases. CONCLUSIONS: Peritonitis immediately following PEG
      insertion is rarely due to the air leakage during insertion (benign
      pneumoperitoneum) and warrants early laparotomy to identify and correct the
      likely associated visceral trauma. Following PEG tube change peritonitis may
      result from stomal separation or tube malposition and an urgent study is
      indicated to identify the cause.

PMID- 9572336
TI  - Resource utilization by injured automobile occupants and pedestrians.
AB  - BACKGROUND: This study was designed to test the hypothesis that the hospital
      resources utilized in treating pedestrian trauma would be significantly greater
      than that for automobile occupants. This was based on previous studies that
      showed that the demographic features and patterns of injury sustained by the
      pedestrian population were significantly different from that of automobile
      occupants. METHODS: A hospital-based study was designed utilizing retrospective
      analysis of a prospective trauma database. All primary retrievals of pedestrians
      (n=547) and automobile occupants (n=597) involved in accidents in Central Sydney
      from mid-1990 to mid-1995 were included. The length of hospital stay, use of the
      intensive care unit (ICU) and visits to the operating theatre (Standard Resource
      Cost) were compared. RESULTS: The age and injury severity scores were
      significantly higher for the pedestrian group. The length of stay (days) for the
      pedestrians (mean, 12 SD 14; median, 7 interquartile range (IQR) 13), was
      significantly higher (P < 0.0001 ) than that for the automobile occupants (mean,
      7 SD 11; median, 2 IQR 6). The ICU utilization (days) for the pedestrians (mean,
      1.3 SD 4.0; median, 0) was significantly higher (P < 0.0001) than that of the
      automobile occupants (mean, 0.6 SD 2.9; median, 0). The average operating theatre
      utilization per pedestrian (0.65 visits) exceeded that of automobile occupants
      (0.43) by 50% (P < 0.0001). CONCLUSIONS: The study confirms that the acute care
      of pedestrian injury utilizes more hospital resources than that of automobile
      occupants. Resources should be allocated to meet this need both in terms of
      hospital reimbursement and overall directives in public health policy.

PMID- 9572337
TI  - Cadaveric liver procurement using aortic perfusion only.
AB  - BACKGROUND: To test the effectiveness of a simpler surgical technique for
      cadaveric liver procurement for liver transplantation, a prospective randomized
      study was carried out between August 1994 and December 1995, to compare aortic
      perfusion only (APO) for flush-preservation of the liver with the conventional
      combined aortic and portal perfusion (APP) technique. METHODS: Forty multiple
      organ donors were enrolled with 20 in each arm of the trial. Donor parameters
      (age, bodyweight, liver function tests), surgeons performing the operations, the
      involvement of other procurement teams and the total ischaemic times were similar
      in the two groups. The liver recipients had a wide range of native liver
      pathology but were of similar age, sex and bodyweight in the two groups. RESULTS:
      The mean procurement operation times for the APO and APP groups were 126.7+/-38.6
      and 137.8+/-55.9 min, respectively (P=ns). The perfusion took longer to complete
      in the APO group (10.2+/-1.7 vs 7.2+/-1.4 min (APP), P < 0.001). The liver
      temperature fell to its lowest level (12.5+/-3.4 degrees C (APO) vs 11+/-3
      degrees C (APP), P=ns) in a similar time (11.9+/-3.8 min (APO) vs 9.3+/-3.4 mins
      (APP), P=ns). There was no graft primary non-function or graft arterial injury in
      either group. There was no significant difference between the APO and APP initial
      graft outcomes. The 3-month patient survival rate was identical in the two groups
      (95%); 81% of renal grafts from the APO donors functioned well from the time of
      transplantation as did 76% of those from APP donors. CONCLUSIONS: It is concluded
      that the APO procurement technique produces equivalent results to those achieved
      with the APP method. The simplicity of the APO technique makes it the preferred
      technique.

PMID- 9572338
TI  - Peristalsis in an interposed colonic segment immediately following total
      oesophagogastrectomy.
AB  - BACKGROUND: The motility pattern of colon used for oesophageal replacement in an
      oesophagogastrectomy is thought to be altered following interposition. Whether
      this is the result of adaptation or the removal of motor control mechanisms is
      unknown. Motility patterns of the interposed colon during the immediate
      postoperative period have not been previously studied. METHODS: A patient who had
      an oesophageal adenocarcinoma and an unhealed gastric ulcer, underwent total
      gastrectomy and oesophagectomy. A colonic segment oriented isoperistaltically was
      used for oesophageal replacement. During the surgery, a customized 10 channel
      motility catheter was introduced transnasally into the colonic segment, and 24 h
      after surgery measurement of motor activity was undertaken using a perfused
      manometric system. RESULTS: Peristaltic contractions were observed with a mean
      contraction amplitude of 39.6 mmHg in the proximal channel, 90.3 mmHg in the
      distal channel and a mean propagation velocity of 0.51 cm/s. CONCLUSIONS:
      Peristaltic colonic contractions continue to occur in the early postoperative
      period in the colonic segment used to replace the oesophagus. In view of this,
      colon replacing the oesophagus should always be arranged in an isoperistaltic
      fashion.

PMID- 9572339
TI  - Laparoscopic gastrostomy: towards the ideal technique.
AB  - BACKGROUND: Laparoscopic gastrostomy is the best option for long-term gastric
      intubation when percutaneous endoscopic gastrostomy is not possible. The ideal
      technique is yet to be defined. METHODS: A technique of suturing the gastric wall
      to the posterior rectus sheath under direct vision has been developed. The method
      is simple and avoids the difficulties and potential complications described with
      other techniques. RESULTS: The technique has been used in three cases with
      excellent results and no complications. CONCLUSION: The described technique is a
      further advance in defining the 'ideal' technique of laparoscopic gastrostomy.

PMID- 9572340
TI  - Computers in medical education 1: evaluation of a problem-orientated learning
      package.
AB  - BACKGROUND: A computer-based learning package has been developed, aimed at
      expanding students' knowledge base, as well as improving data-handling abilities
      and clinical problem-solving skills. The program was evaluated by monitoring its
      use by students, canvassing users' opinions and measuring its effectiveness as a
      learning tool compared to tutorials on the same material. METHODS: Evaluation was
      undertaken using three methods: initially, by a questionnaire on computers as a
      learning tool and the applicability of the content: second, through monitoring by
      the computer of student use, decisions and performance; finally, through pre- and
      post-test assessment of fifth-year students who either used a computer package or
      attended a tutorial on equivalent material. RESULTS: Most students provided
      positive comments on the learning material and expressed a willingness to see
      computer-aided learning (CAL) introduced into the curriculum. Over a 3-month
      period, 26 modules in the program were used on 1246 occasions. Objective
      measurement showed a significant gain in knowledge, data handling and problem
      solving skills. CONCLUSIONS: Computer-aided learning is a valuable learning
      resource that deserves better attention in medical education. When used
      appropriately, the computer can be an effective learning resource, not only for
      the delivery of knowledge. but also to help students develop their problem
      solving skills.

PMID- 9572341
TI  - The role of the journal club in surgical training.
AB  - BACKGROUND: The development of skills in critical appraisal of the medical
      literature is an important aspect of surgical training. METHODS: At the Prince of
      Wales Hospital a journal club has been conducted for more than 5 years to improve
      the registrars' training in this area. A questionnaire was circulated regarding
      the success of the journal club at achieving adequate review of the important
      current literature, development of critical appraisal skills by registrars and
      providing a convivial social gathering. RESULTS: A total of 28 out of 39 current
      or previous journal club members responded to the questionnaire. Twenty-three of
      the respondents felt that the journal club provided a good to excellent review of
      current literature, 26 felt that the journal club facilitated development of
      critical appraisal skills and all 28 said that the journal club was a convivial
      social forum. Eight research projects developed from journal club reviews, 19 of
      the respondents reported that their clinical practice had changed, and 19 had
      been stimulated to further review a topic as a result of the journal club. Many
      of the respondents had specific criticisms of the journal club, and these have
      been used to improve the journal club format. CONCLUSIONS: The present study has
      highlighted the strengths and weaknesses of our journal club. The journal club is
      a valuable component of surgical education.

PMID- 9572342
TI  - Leeches in medicine.

PMID- 9572343
TI  - Pioneer flying surgeons in Australia.

PMID- 9572344
TI  - Colorectal diseases: comment.

PMID- 9572345
TI  - Use of a posterior Boari flap in ureteral replacement.

PMID- 9572346
TI  - Bilateral Kienbock's disease in a patient on haemodialysis.

PMID- 9572347
TI  - Invasive lobular carcinoma in an axillary breast.

PMID- 9572348
TI  - Renal cell carcinoma metastatic to the thyroid.

PMID- 9572349
TI  - Intra-operative radiotherapy in the management of a case of high-grade sarcoma.

PMID- 9572350
TI  - Intergenerational exchanges and perceptions of support within "boomerang kid"
      family environments.
AB  - Drawing on the social exchange perspective, we examine: 1) the extent to which
      adult children who have returned to the parental home ("boomerang kids") exchange
      several types of instrumental and affective support with their parents, and 2)
      whether there is symmetry or incongruence in perceptions of support among these
      family dyads. The data used for this study are drawn from interviews with one
      child and one parent from 218 families in which the child has recently returned
      home. Findings indicate that children receive more frequent instrumental and
      emotional (affective) support than parents receive, and that parents perceive
      that they receive considerably more emotional support than boomerang children
      acknowledge donating. Implications for family relationships over the life course
      and household living arrangements are considered.

PMID- 9572351
TI  - Age identification: a comparison between Finnish and North-American cultures.
AB  - This study examined perceptions of age among Finnish males and females in three
      age groups; twenty-five to thirty-nine-year-olds (n = 446), forty to fifty-four
      year-olds (n = 482) and fifty-five to sixty-four-year-olds (n = 427). The age
      perceptions of the Finnish sample were further compared with those of a North
      American sample with corresponding age groups (n = 169, n = 187, n = 222)
      reported by Barak, Stern, and Gould (1988). Four age concepts used were
      chronological age, subjective age, ideal age, and disparity age. As expected on
      the basis of previous studies in age identification, no difference was found
      between Finnish males and females in terms of subjective age. Ideal age, however,
      differentiated Finnish males and females; the age ideal of females was
      significantly higher when compared with males with respective chronological ages.
      The comparison between Finnish and North-Eastern U.S. sample indicated that the
      latter group had more youthful age identity while the Finns expressed a greater
      acceptance of their present age status. This was seen in higher subjective and
      ideal ages of Finns when compared with their North-American counterparts. Socio
      cultural differences in terms of meanings associated with chronological age and
      aging are discussed.

PMID- 9572352
TI  - Cultural influences on caregiving burden: cases of Koreans and Americans.
AB  - This study compared cultural influences on caregiver burdens of Korean adult
      children and American adult children caring for parents with dementia, and
      identified culturally specific values, norms, and customs associated with low or
      high burden. The findings suggested that the low burden of the Korean caregivers
      was associated with extended family support and high filial responsibility while
      that of the American caregivers was related to the use of formal services and
      high gratification from caregiving. Obversely, the high burden of the Koreans was
      seen to be associated with limited formal services outside the family and low
      gratification from caregiving for in-laws while that of the Americans was
      suggested to be due to limited extended family support and low filial
      responsibility. Needs for culturally-appropriate interventions are discussed.

PMID- 9572353
TI  - An empirical study of object relations in adult children of depressed elderly
      mothers.
AB  - This study used a psychodynamic perspective on psychological functioning, object
      relations, for understanding coping and emotional distress in (N = 50) sons and
      daughters providing assistance to an elderly mother hospitalized for major
      depression. Hypotheses that better maternal object relations would be related to
      more adaptive coping and less emotional distress received partial support. The
      hypothesis that an elderly mother's history of depression when a son or daughter
      was a child would be associated with adult children's poorer object relations
      received support. Results indicate that object relations may be a useful
      framework for studying family issues in late life depression.

PMID- 9572354
TI  - Bed-ridden elderly in Japan: social progress and care for the elderly.
AB  - The demand for health care and social welfare services for the elderly has
      increased and in Japan, there is a need in the social system to improve the
      quality of life, especially for those who are disabled. This article directs
      attention to bed-ridden elderly persons from the standpoint of social problems
      attending economic development and population changes based on data from Japan,
      the United States, Sweden, and OECD countries. Compared to the United States,
      there are more bed-ridden elderly in Japan, and inadequate public resources for
      caring. Physicians, nurses, care workers, and rehabilitation specialists such as
      physiotherapist and occupational therapist per 1000 aged sixty-five or over are
      89.5 in Japan while 237.4 in Sweden. Japan has the fewest such health and welfare
      personnel among developed countries. Even with increases in such personnel
      through the New Gold Plan, future increase in aged population would off-set the
      effect and the problem of providing care for the elderly remains.

PMID- 9572356
TI  - Combinatorial expression patterns of individual TLE proteins during cell
      determination and differentiation suggest non-redundant functions for mammalian
      homologs of Drosophila Groucho.
AB  - The Drosophila protein Groucho is involved in the regulation of cell
      determination events during insect neurogenesis and segmentation. A group of
      mammalian proteins, referred to as transducin-like Enhancer of split (TLE) 1
      through 4, share with Groucho identical structures and molecular properties. The
      aim was to determine whether individual TLE proteins participate in the
      regulation of cell determination in mammals like their Drosophila counterpart. It
      is here reported that TLE family members are expressed in combinatorial ways
      during the in vitro differentiation of mouse P19 embryonic carcinoma cells (a
      model for neural determination) and rat CFK2 cells (a model for chondrocytic
      determination). TLE1 is up-regulated and TLE2 and TLE4 are down-regulated to
      different extents during early stages of differentiation. In contrast, later
      stages correlate with up-regulation of TLE2 and TLE4, and decreased expression of
      TLE1. Individual TLE proteins are also expressed in combinatorial as well as
      complementary patterns during the development of the cerebral cortex and spinal
      cord of mouse embryos. In particular, TLE1 is robustly expressed in both neural
      progenitor cells and postmitotic neurons of the outer layers of the cortical
      plate, whereas TLE4 expression marks preferentially postmitotic neurons of the
      inner layers. Taken together, these results strongly suggest non-redundant roles
      for individual TLE proteins during both cell-determination and cell
      differentiation events.

PMID- 9572355
TI  - Genetic evidence for posterior specification by convergent extension in the
      Xenopus embryo.
AB  - Genetic studies substantiate that mesodermal convergent extension expressed
      behind the anteroposterior borderline, in the form of a gradient with the
      posterior apex after gastrulation, regulates morphogenesis of the posterior zone
      at the dorsal and dorso-lateral levels which is in full agreement with the model
      of dorsalization-caudalization. In contrast, how anteroposterior specification of
      mesodermal tissues occurs at the ventral and latero-ventral levels is not yet
      understood.

PMID- 9572357
TI  - Evidence for specific RNA/protein interactions in the differential segment of the
      W sex chromosome in the amphibian Pleurodeles waltl.
AB  - Pleurodeles exhibits a ZZ/ZW system of GSD (genotype sex determination). However,
      the Z and W sex chromosomes appear to be morphologically identical. A short RNA
      sequence is described that was specifically bound to lampbrush loops in the
      differential segment of the sexual bivalent IV. The distribution of these labeled
      loops in experimentally produced ZZ and WW females enabled us to demonstrate that
      such labeled loops were perfectly correlated with the W chromosome. Therefore,
      this RNA sequence constitutes an excellent marker for the W differential segment.
      Furthermore, analysis of the labeled loops under various experimental conditions
      suggested that their labeling is caused by specific interactions between this RNA
      sequence and lampbrush loop-associated proteins (RNA/protein interactions). North
      western assays revealed that nuclear polypeptide(s) of 65 kDa could be
      responsible for such binding.

PMID- 9572358
TI  - Crossregulation between En-2 and Wnt-1 in chick tectal development.
AB  - En-1, En-2 and Wnt-1 are proposed to be essential signals for the development of
      the optic tectum in chick embryos. Drosophila engrailed and wingless, homologs of
      En (En-1 and En-2) and Wnt-1, respectively, have been shown to crossregulate each
      other. In the present paper, it is reported that crossregulation between En-2 and
      Wnt-1 is preserved in the development of the chick optic tectum. When En-2 is
      overexpressed by the replication competent retroviral vector, Wnt-1 is expressed
      ectopically at the dorsal midline of the diencephalon. When Wnt-1 is introduced
      extrinsically either by ectopic transplantation of mesencephalon, or by
      implantation of Wnt-1 producing cells, En-2 is induced ectopically at the dorsal
      midline of the tel-diencephalic border. Thus, ectopic expression of En-2 and Wnt
      1 leads to crossregulation of each other in the chick brain. As diencephalon
      transdifferentiates into the optic tectum by an appropriate signal, the
      crossregulation of En-2 and Wnt-1 in the diencephalon may mimic the relationship
      required for early development in the tectum.

PMID- 9572359
TI  - Early embryonic interaction of retinal pigment epithelium and mesenchymal tissue
      induces conversion of pigment epithelium to neural retinal fate in the silver
      mutation of the Japanese quail.
AB  - The neural retina and retinal pigment epithelium (RPE) diverge from the optic
      vesicle during early embryonic development. They originate from different
      portions of the optic vesicle, the more distal part developing as the neural
      retina and the proximal part as RPE. As the distal part appears to make contact
      with the epidermis and the proximal part faces mesenchymal tissues, these two
      portions would encounter different environmental signals. In the present study,
      an attempt has been made to investigate the significance of interactions between
      the RPE and mesenchymal tissues that derive from neural crest cells, using a
      unique quail mutant silver (B/B) as the experimental model. The silver mutation
      is considered to affect neural crest-derived tissues, including the epidermal
      melanocytes. The homozygotes of the silver mutation have abnormal eyes, with
      double neural retinal layers, as a result of aberrant differentiation of RPE to
      form a new neural retina. Retinal pigment epithelium was removed from early
      embryonic eyes (before the process began) and cultured to see whether it
      expressed any phenotype characteristic of neural retinal cells. When RPE of the
      B/B mutant was cultured with surrounding mesenchymal tissue, neural retinal cells
      were differentiated that expressed markers of amacrine, cone or rod cells. When
      isolated RPE of the B/B mutant was cultured alone, it acquired pigmentation and
      did not show any property characteristic of neural retinal cells. The RPE of wild
      type quail always differentiated to pigment epithelial cells. In the presence of
      either acidic fibroblast growth factor (aFGF) or basic FGF (bFGF), the RPE of the
      B/B mutant differentiated to neural retinal cells in the absence of mesenchymal
      tissue, but the RPE of wild type embryos only did so in the presence of 10-40
      times as much aFGF or bFGF These observations indicate that genes responsible for
      the B/B mutation are expressed in the RPE as well as in those cells that have a
      role in the differentiation of neural crest cells. They further suggest that
      development of the neural retina and RPE is regulated by some soluble factor(s)
      that is derived from or localized in the surrounding embryonic mesenchyme and
      other ocular tissues, and that FGF may be among possible candidates.

PMID- 9572360
TI  - Metamorphosis-associated and region-specific expression of calbindin gene in the
      posterior intestinal epithelium of Xenopus laevis larva.
AB  - The present study used a molecular approach toward understanding the mechanism of
      hormone- and region-dependent remodeling of the small intestine during
      metamorphosis of Xenopus laevis. A protein spot was noticed on a two-dimensional
      polyacrylamide gel as a protein whose expression was metamorphic stage- and
      region-dependent. The protein was identified as the Xenopus homolog (Xcalbindin)
      of chick calbindin D28k. Xcalbindin expression in the intestine was restricted to
      absorptive cells in the posterior part, being detectable at stages 49-61, not
      detectable at stages 62-63, detectable again at stages 64-66, and finally
      becoming undetectable in the adult. During spontaneous metamorphosis, the level
      of Xcalbindin mRNA was significantly increased between stages 57 and 58,
      dramatically reduced at stage 59, and the mRNA was undetectable from stages 60
      63, after which it was weakly re-expressed until the end of metamorphosis. Such
      up- and down-regulation of Xcalbindin mRNA was induced precociously by exogenous
      thyroid hormone. These results indicated that Xcalbindin is a specific marker of
      the differentiated absorptive cells of the intestine. Immunohistochemistry with
      specific antibodies against Xcalbindin demonstrated that precursor cells of adult
      intestinal epithelial cells expressed Xcalbindin. Considering these results, the
      origin of adult intestinal epithelial cells was discussed.

PMID- 9572361
TI  - Blastomeres show differential fate changes in 8-cell Xenopus laevis embryos that
      are rotated 90 degrees before first cleavage.
AB  - To study the mechanisms of dorsal axis specification, the alteration in dorsal
      cell fate of cleavage stage blastomeres in axis-respecified Xenopus laevis
      embryos was investigated. Fertilized eggs were rotated 90 degrees with the sperm
      entry point up or down with respect to the gravitational field. At the 8-cell
      stage, blastomeres were injected with the lineage tracers, Texas Red- or FITC
      Dextran Amines. The distribution of the labeled progeny was mapped at the tail
      bud stages (stages 35-38) and compared with the fate map of an 8-cell embryo
      raised in a normal orientation. As in the normal embryos, each blastomere in the
      rotated embryos has a characteristic and predictable cell fate. After 90 degrees
      rotation the blastomeres in the 8-cell stage embryo roughly switched their
      position by 90 degrees, but the fate of the blastomeres did not simply show a 90
      degrees switch appropriate for their new location. Four types of fate change were
      observed: (i) the normal fate of the blastomere is conserved with little change;
      (ii) the normal fate is completely changed and a new fate is adopted according to
      the blastomere's new position: (iii) the normal fate is completely changed, but
      the new fate is not appropriate for its new position; and (4) the blastomere
      partially changed its fate and the new fate is a combination of its original fate
      and a fate appropriate to its new location. According to the changed fates, the
      blastomeres that adopt dorsal fates were identified in rotated embryos. This
      identification of dorsal blastomeres provides basic important information for
      further study of dorsal signaling in Xenopus embryos.

PMID- 9572362
TI  - Activin-treated ectoderm has complete organizing center activity in Cynops
      embryos.
AB  - The differentiation and organizer activity of newt ectoderm treated with activin
      A was studied in explantation and transplantation experiments. In the
      explantation experiments, ectoderm dissected from late morulae-early gastrulae
      stage embryos treated with a high concentration of activin A (100 ng/mL) formed
      only yolk-rich endodermal cells. Mesodermal tissues, such as notochord and
      muscle, were seldom found in these explants. When they were transplanted into the
      blastocoele of other early gastrulae, they formed part of the endoderm of the
      host embryo and induced a secondary axis with only posterior characters
      (including axial mesoderm and neural tissues). In contrast, whole secondary axes
      were induced when activin-treated ectoderm was transplanted into the ventral
      marginal zone (VMZ) of early blastulae. The transplanted pieces invaginated by
      themselves and differentiated into foregut structures including pharynx, stomach,
      and liver. These phenomena were also observed in experiments in which presumptive
      foregut was used instead of activin-treated ectoderm. These findings show that
      activin-treated ectoderm can act as the complete organizing center in Cynops.

PMID- 9572363
TI  - Hypoblast cells of chick pre-streak stage embryos invaded basement membrane
      analogues in vitro: implications for hypoblast layer formation.
AB  - In early chick blastodermal morphogenesis, the hypoblast layer is organized
      beneath the epiblast and induces an axial structure. However, the origin of
      hypoblast cells and the mechanism of hypoblast layer formation are poorly
      understood. We hypothesized that the hypoblast layer is formed by an invasive
      process across the basement membrane of the juxtaposing epiblast, and tested the
      idea in vitro. Primary and secondary hypoblast cells from embryos at various pre
      streak stages were dissociated into single cells and cultured on reconstituted
      basement membrane gel, laminin gel or fibronectin gel in the culture medium with
      or without serum for 24-48 h. As a result, we found that after 24h of serum
      supplemented culture, up to 35% of the hypoblast cells dissolved the gel and made
      holes on it. Similarly, up to 36% of the hypoblast cells showed invasiveness
      after 48 h in the serum-free culture. Furthermore, it was observed that Koller's
      sickle cells, which are regarded to be the progenitors of secondary hypoblast
      cells, penetrated those gels on which they were seeded. The posterior epiblast
      cells covering Koller's sickle were also invasive. These results suggest that the
      presumptive primary hypoblast cells that are known to mingle with epiblast cells
      invade through the basement membrane to form the hypoblast layer. Furthermore,
      the present results imply that invasion through the basement membrane may be
      involved in the formation of Koller's sickle, the anlage of secondary hypoblast.

PMID- 9572364
TI  - Inhibition of sea urchin fertilization by jaspisin, a specific inhibitor of
      matrix metalloendoproteinase.
AB  - Jaspisin, originally isolated from a marine sponge as an inhibitor of the
      hatching of the sea urchin (Hemicentrotus pulcherrimus) embryo, causes inhibition
      of sea urchin fertilization. Electron microscopic examination revealed that the
      acrosome reaction was induced in jaspisin-treated sperm when they were incubated
      with an intact egg. The acrosome-reacted sperm bound to the vitelline layer by
      the acrosomal material surrounding the acrosomal process. However, fusion of the
      acrosomal process and the egg plasma membrane failed to take place. Membrane
      potential changes were monitored using eggs preloaded with a membrane potential
      sensitive fluorochrome, di-8-ANEPPS. Depolarization of the membrane potential,
      normally observed in the fertilized egg was not observed in the egg inseminated
      in the presence of jaspisin, indicating the absence of electrical continuity
      between the jaspisin-treated egg and sperm. Jaspisin inhibited the activities of
      matrix metallo-endoproteinase members but not of other types of proteinases.
      These results provide strong, albeit indirect, evidence that a matrix metallo
      endoproteinase(s) is involved in the process of gamete fusion during sea urchin
      fertilization.

PMID- 9572365
TI  - Crosstalk between the phosphatidylinositol cycle and MAP kinase signaling
      pathways in Xenopus mesoderm induction.
AB  - Recent studies have established a role for the phosphoinositide (PI) cycle in the
      early patterning of Xenopus mesoderm. In explants, stimulation of this pathway in
      the absence of growth factors does not induce mesoderm, but when accompanied by
      growth factor treatment, simultaneous PI cycle stimulation results in profound
      morphological and molecular changes in the mesoderm induced by the growth factor.
      This suggests the possibility that the PI cycle exerts its influence via
      crosstalk, by modulating some primary mesoderm-inducing pathway. Given recent
      identification of mitogen-activated protein kinase (MAPK) as an intracellular
      mediator of some mesoderm-inducing signals, the present study explores MAPK as a
      potential site of PI cycle-mediated crosstalk. We report that MAPK activity, like
      PI cycle activity, increases in intact embryos during mesoderm induction.
      Phosphoinositide cycle stimulation during treatment of explants with basic
      fibroblast growth factor (bFGF) synergistically increases late-phase MAPK
      activity and potentiates bFGF-induced expression of Xbra, a MAPK-dependent
      mesodermal marker.

PMID- 9572366
TI  - Cloning and in situ hybridization analysis of estrogen receptor in the developing
      gonad of the red-eared slider turtle, a species with temperature-dependent sex
      determination.
AB  - Many reptiles exhibit temperature-dependent sex determination where the
      incubation temperature of the egg determines the gonadal sex of the individual.
      If exogenous estrogen is administered during the temperature-sensitive period to
      embryos incubating at a male-producing temperature, the temperature effects can
      be overridden and females will be produced. Inhibiting production of endogenous
      estrogens at female-biased incubation temperatures results in embryos developing
      as males rather than females. Thus, estrogen-estrogen receptor-dependent
      mechanisms appear to play a key role in female sex determination. The present
      study characterized the expression of the estrogen receptor during the critical
      period of temperature sensitivity in the red-eared slider turtle, Trachemys
      scripta. Polymerase chain reaction was used to amplify estrogen receptor cDNA. A
      portion of the estrogen receptor cDNA was used to produce probes for in situ
      hybridization analyses to localize and quantitate levels of estrogen receptor
      mRNA at different stages of development in embryos from different incubation
      temperatures. Estrogen receptor mRNA is expressed in the gonadal tissues of both
      putative males and putative females even before the gonads begin to resolve as
      ovaries or testes. There is a greater abundance of estrogen receptor mRNA in
      putative females at the beginning of the temperature-sensitive period as compared
      to putative males. In embryos from a female-producing incubation temperature,
      levels of estrogen receptor mRNA are higher in the beginning of the temperature
      sensitive window compared to levels after the ovary is differentiated. These
      results support the hypothesis that estrogen-estrogen receptor dependent
      processes are important during sex determination and gonadal differentiation in
      temperature-dependent sex determination.

PMID- 9572367
TI  - Long QT syndrome manifested as fetal ventricular tachycardia and intermittent AV
      block.
AB  - A case of long QT syndrome diagnosed in the early neonatal period is described.
      This full-term female baby had intermittent atrioventricular (AV) block and
      ventricular tachycardia detected antenatally at the gestational age of 26 weeks.
      Sinus rhythm with prolonged QT interval (QTc = 0.636 sec) was found soon after
      birth. She developed variable degree of AV block with alternating left and right
      bundle branch block, which suggested the presence of multilevel AV block. Her
      mother had no lupus autoantibodies. Auditory brain stem evoked potential was
      normal. Family study revealed QT prolongation in her grandmother. Her condition
      improved after pacemaker implantation and oral beta-blocker usage.

PMID- 9572368
TI  - Selective feticide in twin pregnancies with very early preterm premature rupture
      of membranes.
AB  - Nine consecutive multichorionic multiple gestations with early second-trimester
      (< or =20 weeks) preterm premature rupture of the membranes (PPROM) of the lower
      gestational sac were managed expectantly. Mean gestational age at PPROM was 17.5
      weeks (13-20 weeks), and the mean PPROM delivery time interval was 6.2 weeks (0
      11 weeks). A fetal loss of 63% (12 of 19), and a subsequent neonatal loss of 57%
      (4 of 7) were observed. Of the four pregnancies evolving beyond 25 weeks, three
      delivered before 30 weeks. The baby take-home rate was 16% (3 of 19). Histologic
      evidence of chorioamnionitis was present in 5 of 7 (71%) investigated
      pregnancies. Three other consecutive twin pregnancies were complicated by PPROM
      of the precervical gestational sac at 13 to 16 weeks of gestation (mean: 15
      weeks). In the absence of clinical chorioamnionitis and amniotic fluid, selective
      feticide with potassium chloride was performed. Pregnancy was successfully
      prolonged beyond 33 weeks in two cases. The overall PPROM delivery time interval
      was 21 weeks (20-22 weeks). No neonatal losses were encountered. The baby take
      home rate was 66% (2 of 3). Selective feticide of the fetus with early
      midtrimester PROM in the absence of maternal signs of infection may improve the
      former unfavorable pregnancy outcome.

PMID- 9572369
TI  - Coxsackievirus B1 infection in infants less than 2 months of age.
AB  - Most of the neonatal enteroviral infections reported in the literature are
      associated with Coxsackievirus B2-B5 and echovirus 9 and 11. We report a
      retrospective Coxsackievirus B1 (CB1) infection in infants less than 2 months of
      age. Seventeen patients had aseptic meningitis and 8 had systemic sepsis (multi
      organ involvement including meningitis, impaired liver function, and abnormality
      in coagulation). The symptoms and signs were nonspecific and could not be
      distinguished with bacterial infection on clinical grounds. Virus isolation was
      mandatory for diagnosis. Impaired liver function and coagulation profiles were
      noted in patients with systemic sepsis, but not in patients with meningitis only.
      CSF examination showed some uncommon features of viral meningitis: predominance
      of polymorphonuclear cells (PMN) was noted in 62.5% of patients and
      hypoglycorrhachia in 64% of patients. The patients with only meningitis recovered
      completely without any sequela. One of the eight patients with systemic sepsis
      died with case fatality rate 12.5%. Physicians should be aware of the possibility
      of CB1 virus infection in young infants during prevalent seasons. Specimens
      should be sent for viral culture in patients with meningitis and sepsis to make a
      definite diagnosis.

PMID- 9572370
TI  - Feto-neonatal ultrasonography to detect renal abnormalities: evaluation of 1-year
      screening program.
AB  - To determine the accuracy of antenatal renal pelvis measurement as a screening
      tool for renal anomalies we reviewed the antenatal ultrasounds performed at our
      institution over 1 year. Renal pelvis dilation was found in 3.8% of pregnancies
      followed by our obstetrics department. In nine (17.6%) infants renal anomalies
      were detected after birth, the remaining cases remained unchanged or resolved
      over a 1-year postnatal follow-up. In our series dilations of less than 10 mm in
      utero resolved in the first months after birth while dilations greater than 15 mm
      were all associated with malformations of the genitourinary tract. The choice of
      the most appropriate follow-up for dilations between 10 and 15 mm remains an
      issue because these dilations can herald renal anomalies.

PMID- 9572371
TI  - The incidence of colorectal cancer during pregnancy in Japan: report of two cases
      and review of Japanese cases.
AB  - Colorectal cancer during pregnancy is very rare. We report two additional cases
      of rectal carcinoma. A 34-year-old woman with an obstructive adenocarcinoma of
      the rectal region was diagnosed at labor. A 35-year-old woman with an
      adenocarcinoma of the rectal region was diagnosed at 32 weeks of gestation and
      underwent a cesarean section and rectal resection at 35 weeks of gestation. A
      retrospective review of the Japanese literature was performed to identify
      patients who appeared to have primary colorectal cancer during pregnancy. Thirty
      six patients with colon cancer (75.0%), 10 (20.8%) with rectal cancer, and two
      (4.2%) of unknown sites have been reported in Japanese series. The average age of
      the mother was 32.2 years. The calculated incidence of colorectal cancer among
      Japanese pregnant women was one case per 502,316 live births during the years
      between 1986 through 1995. Although the majority of colorectal cancers diagnosed
      during pregnancy are rectal carcinomas, the patients in Japan were predominantly
      complicated by colon cancer. The fetal risk seems small, because there were no
      cases of colorectal cancer metastatic to the products of conception.

PMID- 9572372
TI  - Declines in patient volume: an obstetrics and gynecology teaching program's
      response.
AB  - Historically, University teaching hospitals have been the primary providers of
      health care to the indigent population. With the advent of managed health-care
      plans, the university hospitals have seen a rapid decline in their obstetrical
      patient populations. This decrease is reflected in the numbers of deliveries and
      gynecological surgeries. From 1990 to 1995, these changes resulted in a
      significant decline in deliveries at our hospital, the Lyndon B. Johnson General
      Hospital. To reverse this ominous trend, we instituted a variety of changes
      resulting in a more patient-centered system and found an improvement in the
      numbers of obstetrical patients. In the following report, we describe these
      changes and the subsequent outcome.

PMID- 9572373
TI  - Tocolysis of preterm contractions does not improve preterm delivery rate or
      perinatal outcomes.
AB  - To determine whether hospital admission and parenteral tocolysis of patients with
      threatened preterm labor results in a decreased preterm delivery rate and
      improved perinatal outcome, we performed a prospective cohort study comparing
      tocolytic treatment versus no tocolytic treatment. Women between 20 and 37 weeks'
      gestation who presented with at least eight uterine contractions per hour and a
      cervical examination <2 cm dilated, <80% effaced, and no cervical change over a 2
      hr period were entered into the study. Exclusion criteria included cervical
      change, multiple gestation, chorioamnionitis, rupture of membranes, placenta
      previa or abruption, undiagnosed vaginal bleeding, and prior tocolytic therapy in
      the current pregnancy. Seventy-five patients were admitted to the hospital for
      tocolysis (tocolysis cohort) and 81 were observed and discharged to home
      (observation cohort). There was no significant difference in mean gestational age
      at delivery, mean birth weight, or in preterm delivery rate between the two
      cohorts. Four of the eight women in the observation cohort who delivered preterm
      had a history of preterm delivery. We conclude that discharging women with
      preterm contractions without objective evidence of labor does not result in an
      increase in preterm births. More importantly, tocolysis did not decrease the
      preterm delivery rate in this cohort.

PMID- 9572374
TI  - Isolated lateral ventricular asymmetry in very low-birth-weight infants: a left
      sided lesion?
AB  - We prospectively performed serial cranial ultrasonography to determine the
      incidence of asymmetry of the lateral ventricles in very low-birth-weight (VLBW)
      infants (500-1500 g) who did not have evidence of other intracranial pathology.
      Of the 490 babies scanned, 354 were free of other pathology and 41 (11.6%) had
      isolated ventricular asymmetry. In 10 infants, the asymmetry was seen on the
      initial scan and in 31, it developed subsequently. In 19 infants, the ventricular
      asymmetry resolved and in 22 infants it persisted until hospital discharge. In no
      case was progressive enlargement of the ventricles noted. There was a striking
      tendency of the larger ventricle to be on the left side (33 L>R, 8 R>L). Compared
      with a control group of babies matched for birth weight and gestational age who
      had persistently negative scans, there were no differences in Apgar scores,
      cesarean section rate, gender distribution, prenatal steroid exposure, or
      complications of prematurity except for an increased incidence of respiratory
      distress syndrome requiring surfactant in the group with ventricular asymmetry
      (63% vs. 29%, p = 0.04). Ventricular asymmetry is common in VLBW infants, but
      whether it is an incidental finding or represents subtle brain injury is unknown.

PMID- 9572375
TI  - Disproportionate consumption of ventilator resources by very preterm survivors
      persists in the 1990s.
AB  - The aim of this study of consecutive livebirths between 23 and 30 weeks of
      gestational age was to determine the changes over time in the relationship
      between gestational age and the consumption of nursery resources by surviving
      preterm infants. Three discrete eras, comprising the years 1977-1985, 1986-1990,
      and 1991-1995, were identified, based on availability of ventilators and changes
      in perinatal care. The survival rate rose dramatically with each week's increase
      in gestational age, and increased significantly between successive eras. Overall,
      consumption of resources for assisted ventilation by survivors increased over
      time. In infants born before 28 weeks, for each week of decrease in gestational
      age, survivors averaged an extra 12.9 days of assisted ventilation in 1977-1985,
      13.4 days in 1986-1990, and 13.5 days in 1991-1995, while infants born between 28
      30 weeks of gestational age needed only an extra 2.3 days, 3.3 days, and 4.6 days
      of assisted ventilation for each week of decrease in gestational age in
      successive eras, respectively. There was no indication that improvements in
      perinatal care over time shortened the duration of assisted ventilation for
      surviving preterm infants.

PMID- 9572376
TI  - Central diabetes insipitus in a patient with congenital toxoplasmosis.
AB  - A 33-day-old male infant who developed central diabetes insipitus as a
      complication of congenital toxoplasmosis is presented. He had polyuria and
      hypernatremia on admission and responded to Intranasal desmopressin acetate with
      the normalization of above mentioned findings. Computed tomographic (CT) scan of
      the brain showed obstructive hydrocephaly with periventricular and right basal
      ganglion calcification. CT scan of the pituitary gland, thyroid function tests,
      and serum cortisol levels were all normal. This is the first report of isolated
      diabetes insipitus with congenital toxoplasmosis in literature and central
      diabetes insipitus should be remembered if polyuria and hypernatremia develops in
      a patient with congenital toxoplasmosis.

PMID- 9572377
TI  - Prenatal diagnosis of sirenomelia with bilateral hydrocephalus: report of a
      previously undocumented form of VACTERL-H association.
AB  - Sirenomelia represents a severe developmental field defect of the posterior axis
      caudal blastema, resulting in partial or complete fusion of the lower limb buds.
      The VATER association is a combination of morphological defects including
      vertebral defects, anal atresia, tracheoesophageal fistula, esophageal atresia,
      radial and renal anomalies. The VACTERL-H association is a rare expanded form of
      the VATER association that includes cardiac defects, limb defects, and
      hydrocephalus. It has been suggested that the VATER association may represent a
      less severe form of sirenomelia. In this report, we document a case in which
      prenatal ultrasonography detected simultaneously occurring sirenomelia and
      hydrocephalus. Postmortem radiography and autopsy findings confirmed the prenatal
      diagnosis. To our knowledge, this is the first report of prenatal diagnosis of a
      fetus with these two abnormalities. This report supports the hypothesis that
      VATER association, VACTERL-H association, and sirenomelia may represent
      pathophysiologically related entities.

PMID- 9572378
TI  - Glycosylated hemoglobin in insulin-dependent diabetes mellitus related to
      preeclampsia.
AB  - Preeclampsia may occur due to failure of the second wave of trophoblastic
      invasion between 16 to 20 weeks of gestation. We studied whether the mean value
      of glycosylated hemoglobin (HbA1c) during this gestational period was associated
      with an increased incidence of preeclampsia in insulin-dependent diabetes
      mellitus. We conducted a retrospective study of 131 insulin-dependent diabetes
      mellitus (IDDM) pregnancies with HbA1c values available in medical records over
      the past 10 years. The correlation between high mean HbA1c (>8%) before or after
      20 weeks and the incidence of preeclampsia was determined. Mean HbA1c values
      before 20 weeks were further divided into 10- to 15- and 16- to 20-week
      intervals. Mean values of HbA1c in these different gestational periods were
      analyzed by chi(2) or Fisher's exact tests. P < 0.05 was considered statistically
      significant. We found that IDDM pregnant women with high mean values of HbA1c
      (>8%) had a significantly higher rate of preeclampsia than those with normal mean
      values (45 vs. 24%, p = 0.018). However, we found that IDDM pregnant women with
      an elevated mean HbA1c value at 16-20 weeks', but not 10-15 weeks' or after 20
      weeks', gestation had a significantly higher incidence of preeclampsia than those
      with normal mean HbA1c value (chi(2) = 4.49, p = 0.03). We conclude that a
      significant association between elevated mean HbA1c values at 16-20 weeks'
      gestation and a high frequency of preeclampsia in IDDM pregnancies suggests that
      glycosylated hemoglobin may play an important role in the pathogenesis of
      preeclampsia in IDDM pregnant women.

PMID- 9572379
TI  - Differential developmental process of respective behavioral states in human
      fetuses.
AB  - The presence of behavioral states has been recognized in human fetuses. However,
      developmental process of fetal behavioral states remains to be clarified. In
      thirty-one normal pregnant women between 20 and 41 weeks' gestation, fetal
      movements were examined by using multiple ultrasonic machines. The entire period
      was divided into eye movement (EM), no eye movement (NEM), and unclassified
      periods according to the mode of appearance of rapid eye movements. We
      investigated changes in the ratio of EM and NEM periods and the incidence of
      various fetal movements in these periods. The ratio of EM periods increased
      stepwise between 20 and 32 weeks. The difference in the incidence of "startle"
      and jaw movements between EM and NEM periods was found at 24-27 and 32-35 weeks,
      respectively. We found a significant decrease in the incidence of total body
      movements exclusively in NEM periods at 36-39 weeks and a significant increase in
      the incidence of "rolling" in EM periods at 40-41 weeks. Eye opening was
      ultrasonographically recognized, providing evidence for awake state in the human
      fetus. This study revealed the characteristic appearance of fetal movements as
      related to the presence or absence of EM during the second half of pregnancy, and
      thereby pointed to differential development process of behavioral states of human
      fetuses.

PMID- 9572380
TI  - Sonographic measurement of absolute and relative renal length in adults.
AB  - PURPOSE: The aim of this study was to evaluate sonographically measured absolute
      and relative lengths of normal kidneys according to subject height, sex, and age.
      METHODS: Real-time sonography was performed on 202 subjects. Measurements of
      longitudinal renal diameter represented absolute renal length. Relative renal
      length was calculated using the kidney length: body height ratio (KBR). RESULTS:
      Statistical analyses were done on findings in 175 subjects without renal
      impairment (104 men and 71 women) whose ages ranged from 17 to 85 years (mean +/-
      SD, 46.3 +/- 17.1). The mean heights of the subjects were 176 +/- 7 cm for men
      and 167 +/- 6 cm for women. The left kidney was absolutely (mean +/-SD, 112 +/- 9
      mm) and relatively (mean KBR +/- SD, 0.655 +/- 0.042) longer than the right
      kidney (absolute length, 110 +/- 8 mm; KBR, 0.641 +/- 0.038), regardless of sex
      (p < 0.01). The absolute renal length was significantly greater in men than in
      women for both kidneys (p < 0.01), but there was no significant difference
      between KBRs (p > 0.05). Renal length decreased with age, and the rate of
      decrease seemed to accelerate at 60 years and older. When height and age were
      included in the multivariate regression analysis, sex was not a significant
      predictor of kidney length. CONCLUSIONS: Relative renal length better represents
      kidney size than absolute renal length because it eliminates sex and height
      differences.

PMID- 9572381
TI  - Clinical significance of echogenic amniotic fluid.
AB  - PURPOSE: This study aimed to determine the clinical significance of echogenic
      amniotic fluid. METHODS: We prospectively studied 19 twin pregnancies in which
      the amniotic fluid in 1 sac was anechoic and that in the other sac was echogenic.
      Morphologic characteristics of amniotic fluid were assessed from samples taken at
      amniocentesis or upon delivery within 48 hours after sonographic examination.
      RESULTS: In twins with echogenic amniotic fluid, assessment revealed clear fluid
      in 6 cases (32%), vernix caseosa in 12 (63%), and meconium in 1 (5%). In co-twins
      with anechoic amniotic fluid, assessment revealed clear fluid in 9 cases (47%),
      vernix caseosa in 6 (32%), and meconium in 4 (21%). CONCLUSIONS: Echogenic
      amniotic fluid on prenatal sonography is not predictive of meconium.

PMID- 9572382
TI  - Testicular microlithiasis: association with male infertility.
AB  - PURPOSE: We studied the frequency of testicular microlithiasis (TM) in a select
      group of otherwise healthy infertile men with abnormal semen. METHODS: We
      reviewed scrotal sonography records of 180 consecutive patients with abnormal
      semen who were referred for evaluation of male infertility. The pampiniform
      plexus was evaluated for possible varicocele, and the testes were examined for
      the presence or absence of intratesticular calcifications and/or masses. Five
      patients with more than 5 echogenic foci per transducer field in either testis
      were identified. The medical records and sonograms of this subgroup of patients
      were analyzed. RESULTS: Of the 180 patients, 5 (2.8%) had TM. Three patients with
      TM had concomitant small varicoceles; 2 others had a history of testicular
      maldescent. Two patients eventually became fertile. CONCLUSIONS: Our results
      indicate a higher than expected frequency of TM in otherwise healthy infertile
      men. We speculate that the magnitude of hypospermatogenesis in patients with TM
      is variable and may relate to both the degree of testicular dysgenesis and the
      presence or absence of concomitant scrotal pathology (eg, scrotal varicocele and
      cryptorchidism).

PMID- 9572383
TI  - Sonographic endometrial three-layer pattern in symptomatic first-trimester
      pregnancy: not diagnostic of ectopic pregnancy.
AB  - PURPOSE: We evaluated a recent report that suggested that a "3-layer" appearance
      of the endometrium on sonography is diagnostic of ectopic pregnancy in
      symptomatic pregnant patients. METHODS: We reviewed the log of pelvic sonograms
      performed to rule out ectopic pregnancy in women presenting with first-trimester
      bleeding and/or pain during a 29-month period. Medical records and sonograms of
      patients without sonographic evidence of intrauterine pregnancy were reviewed to
      determine final diagnoses and whether the 3-layer pattern was present. RESULTS:
      One hundred twenty patients with available follow-up had no sonographic evidence
      of intrauterine pregnancy. Fifty-nine (49%) had ectopic pregnancy. An endometrial
      3-layer pattern was noted sonographically in 15 patients (13%), of whom 6 (40%)
      had ectopic pregnancy. As a diagnostic sign of ectopic pregnancy, the endometrial
      3-layer pattern had a sensitivity of 10.2%, specificity of 85.2%, positive
      predictive value of 40%, negative predictive value of 50.5%, and accuracy of
      49.2%. CONCLUSIONS: The endometrial 3-layer pattern is neither sensitive nor
      specific for the diagnosis of ectopic pregnancy.

PMID- 9572384
TI  - Sonographic findings in familial juvenile nephronophthisis-medullary cystic
      disease complex.
AB  - PURPOSE: Familial juvenile nephronophthisis-medullary cystic disease complex (JN
      MCD) is an autosomal inherited renal disease with insidious symptoms that
      ultimately progresses to renal failure. We describe the abnormal sonographic
      findings in JN-MCD at various stages of the disease in a Taiwanese family.
      METHODS: We collected 8 cases in a family via 2 symptomatic index siblings. The
      affected members were 4 males and 4 females whose ages at diagnosis ranged from 1
      to 39 years (mean, 16.8 years). Serial sonographic examinations were performed.
      RESULTS: There were 4 abnormal findings: renal hyperechogenicity, poor
      corticomedullary differentiation, small kidney size, and corticomedullary cysts.
      Renal hyperechogenicity and poor corticomedullary differentiation were found in
      all cases. Renal cysts and reduced renal size sometimes appeared later, after the
      disease had progressed. Three cases had no visualized cysts. CONCLUSIONS: Because
      abnormal renal sonographic findings can be seen long before the appearance of any
      clinical symptoms or signs, sonography is the best technique for diagnosing JN
      MCD and for screening a patient's family.

PMID- 9572385
TI  - Value of contrast-enhanced color Doppler sonography in diagnosing hepatocellular
      carcinoma with special attention to the "color-filled pattern".
AB  - PURPOSE: The purpose of this study is to evaluate the effectiveness of contrast
      enhanced color Doppler sonography in the diagnosis of hepatocellular carcinoma
      (HCC), with special attention to the value of a "color-filled pattern." METHODS:
      Contrast enhancement with Levovist was performed on 30 liver tumors, including 21
      HCCs, as part of phase II and III clinical trials. Detection of a "feeding
      artery" or a "color-filled pattern" with color Doppler sonography was interpreted
      as a positive finding for HCC. Angiography was also performed. RESULTS: A feeding
      artery was detected in 9 HCCs before contrast enhancement and 20 HCCs after. A
      color-filled pattern was seen in 14 HCCs after enhancement. A feeding artery was
      seen in only 1 non-HCC tumor, and a color-filled pattern was not seen in any non
      HCC. The sensitivity and specificity of a feeding artery for the diagnosis of HCC
      were 95% and 89%, values similar to those of hepatic angiography. The sensitivity
      and specificity of a color-filled pattern were 67% and 100%, respectively.
      CONCLUSIONS: Contrast enhancement increases the detectability of a feeding artery
      and improves the sensitivity of color Doppler sonography for diagnosing HCC. A
      color-filled pattern is a highly specific finding in the diagnosis of HCC.

PMID- 9572386
TI  - Agenesis of the internal carotid artery: color Doppler, CT, and MR angiography
      findings.
AB  - Agenesis of the internal carotid artery (ICA) is a rare finding that can lead to
      the false diagnosis of an ICA occlusion. We present the case of a young woman
      with agenesis of the left ICA. Diagnosis was made noninvasively by color Doppler
      imaging (CDI) in combination with high-resolution CT of the base of the skull.
      Magnetic resonance angiography confirmed the diagnosis. CDI in combination with
      CT of the base of the skull allows the diagnosis of ICA agenesis without the use
      of invasive procedures.

PMID- 9572387
TI  - Sonographic findings in a fetus with megacystis-microcolon-intestinal
      hypoperistalsis syndrome.
AB  - We describe the perinatal findings in a female fetus with megacystis-microcolon
      intestinal hypoperistalsis syndrome (MMIHS). Prenatal sonography performed during
      18-21 weeks' gestation showed a normal amount of amniotic fluid, but the fetus
      was seen to have a persistently distended stomach, a hugely distended bladder,
      and bilateral dilated renal calyces. Genetic analysis of amniotic fluid revealed
      a 46,XX karyotype. The pregnancy was terminated at 22 weeks' gestation. At
      necropsy, the fetus was found to have prune-belly syndrome, gastric dilatation,
      pronounced megacystis, bilateral hydronephrosis and megaureters, short bowel,
      microileum, microcolon, and malrotation of the intestines. This fetus showed the
      typical clinical and sonographic features of MMIHS, as well as the rare antenatal
      finding of persistent gastric distention.

PMID- 9572388
TI  - Sonographic diagnosis of seminal vesicle cysts in autosomal dominant polycystic
      kidney disease.
AB  - Multiple, bilateral seminal vesicle cysts were found in a young man by
      transabdominal sonography. Examination of the kidneys disclosed previously
      unknown autosomal dominant polycystic kidney disease. This case report draws
      attention to the rare association between these 2 conditions.

PMID- 9572389
TI  - Complete regression of a congenital splenic cyst.
AB  - We report a congenital splenic cyst that was revealed by prenatal sonography at
      31 weeks' gestation. Serial prenatal sonographic examinations showed a slight
      enlargement of the cyst. However, sonography performed when the infant was 7
      months of age showed the cyst had spontaneously and completely regressed. We
      recommend that practitioners adopt a more conservative approach in such infants,
      one that includes follow-up sonographic examinations, rather than instituting
      interventional treatment.

PMID- 9572390
TI  - Sonographic detection of a stitch abscess.
AB  - A 28-year-old man with a ruptured right Achilles tendon underwent primary end-to
      end suture immediately after injury. Painful swelling developed 6 months later,
      and a lump with discharge from a sinus was observed during physical assessment.
      Sonographic examination with a 10-MHz linear-array transducer demonstrated a
      hypoechoic mass, 8 x 6 mm, within which were 2 markedly echogenic dots. A stitch
      abscess was strongly suspected and was confirmed surgically.

PMID- 9572391
TI  - Prenatal sonographic diagnosis of nuchal edema and double aneuploidy
      (48,XXY,+21): discrepancy between results of chorionic villi and amniotic fluid
      sampling.

PMID- 9572392
TI  - Clinical value of power Doppler sonography in the diagnosis of varicocele.

PMID- 9572393
TI  - A divergent role of COOH-terminal domains in Nurr1 and Nur77 transactivation.
AB  - Orphan nuclear receptors such as Nurr1 and Nur77 have conserved amino acid
      sequences in the zinc finger DNA binding domains and similar COOH-terminal
      regions, but have no known ligands. These receptors can bind DNA sequences
      (response elements) as monomers and can also heterodimerize with the retinoid X
      receptor to activate transcription. We report here the identification and initial
      characterization of a novel COOH-terminal truncated isoform of Nurr1, Nurr1a.
      Internal splicing of Nurr1 generates a frameshift such that a stop codon is
      prematurely encoded resulting in a naturally occurring COOH-terminal truncation.
      Embryonic and postnatal mouse brain showed both Nurr1 and Nurr1a mRNAs expressed
      during development. To characterize essential COOH-terminal elements that may be
      deleted from Nurr1a and determine function in putative ligand binding, we created
      COOH-terminal deletion mutants. Nurr1, Nur77, and 3'-truncated mutants bind in
      gel mobility shift assays to the monomeric Nur77 response element (B1A-RE).
      However, in transient transfection assays, a truncation of as little as 15 Nurr1
      COOH-terminal amino acids diminished transcriptional activation of B1A-thymidine
      kinase-chloramphenicol acetyltransferase reporter. This result was not seen for a
      similar Nur77 deletion mutant, Nur77-586. Unlike full-length Nurr1 and Nur77,
      transactivation by Nur77-586 was not augmented in response to the presence of
      retinoid-like receptor and 9-cis-retinoic acid. Thus, the interaction of putative
      ligand binding and transactivation for Nurr1 and Nur77 may function differently.

PMID- 9572394
TI  - Characterization of a hormone response element in the mouse N-acetyltransferase 2
      (Nat2*) promoter.
AB  - Multiple variant alleles of the human arylamine N-acetyltransferase genes, NAT1*
      and NAT2*, alter the capacity of individuals to metabolize arylamines by N
      acetylation. Although biochemical and genetic studies have improved our
      understanding of the molecular basis of the acetylation polymorphism in humans
      and other mammals, regulation of NAT* gene expression is not understood. In the
      present study, a segment of the 5'-untranslated region of mouse Nat2* was
      sequenced and characterized. Primer extension analysis and RNase protection
      assays exposed multiple transcription initiation sites located 112 to 151 bases
      upstream of the translational start site. Computer sequence analysis revealed a
      promoter-like region located within the region 530 bases upstream of the
      translational start site consisting of TATA boxes, upstream promoter elements
      such as a CAAT box and Sp1 binding site, regulatory elements such as a
      palindromic hormone response element (HRE), and enhancer regions such as an AP-1
      transcription factor binding site. Transient expression of CAT reporter
      constructs of the mouse Nat2*-palindromic HRE demonstrated positive regulation of
      the HSV-thymidine kinase 1 (tk1) promoter and induced the expression of
      chloramphenicol acetyltransferase (CAT). This induction was initiated by the
      addition of hormones such as 5alpha-dihydrotestosterone (DHT) or dexamethasone
      and was entirely dependent on the presence of androgen or glucocorticoid
      receptors, respectively. Together with recent discoveries regarding the effects
      of testosterone on the expression of Nat2* in mouse kidney during development,
      the findings reported in this article suggest that the HRE found in the promoter
      region of Nat2* is a potential candidate for the mediation of androgenic
      regulation of Nat2* in mouse kidney.

PMID- 9572395
TI  - Induction of basic helix-loop-helix protein-containing complexes during erythroid
      differentiation.
AB  - The involvement of basic helix-loop-helix (bHLH) transcription factors in
      erythroid differentiation and development has been established by forced
      expression of the proteins TAL1 and Id1 in cultured cell lines and by targeted
      disruption of the mouse TAL1 gene. To better understand the mechanism by which
      bHLH proteins regulate erythropoiesis, we have investigated HLH protein-DNA
      interactions in mouse erythroleukemia (MEL) cells before and during chemically
      induced differentiation. Three bHLH (E-box) binding activities were found to be
      induced in nuclei from differentiating MEL cells. Using specific antisera, we
      have demonstrated that these complexes are dimers of TAL1 and ubiquitous E
      proteins. Similar complexes were detected in nuclear extracts from a human
      erythroid cell line, K562, and from mouse fetal liver. All three bHLH complexes
      were disrupted in vitro by Id1, a dominant-negative HLH protein that we and
      others have previously shown to antagonize MEL cell differentiation. During
      differentiation of an Id1-overexpressing MEL cell line, induction of a complex
      containing TAL1 and E2A was not only blocked but reduced below the levels seen in
      undifferentiating cells. These observations are consistent with the idea that
      TAL1 and Id1 have opposing effects on erythroid differentiation and that the
      level of TAL1/E2A heterodimer and/or another E protein-containing complex may
      influence the decision of a cell to terminally differentiate.

PMID- 9572396
TI  - The lambda holin accumulates beyond the lethal triggering concentration under
      hyperexpression conditions.
AB  - Most bacteriophages terminate infection by creating lesions in the cytoplasmic
      membrane, which not only cause immediate cell death but also allow escape of a
      phage-encoded endolysin. Destruction of the peptidoglycan and cell lysis follows
      very rapidly, allowing efficient release of the progeny virions. These membrane
      lesions are formed by a small integral membrane protein called a holin. Holins
      have highly charged carboxyl-termini that are thought to have two transmembrane
      alpha-helical domains. Holins are believed to oligomerize and form large holes in
      the inner membrane. The prototype holin is the S protein from bacteriophage
      lambda. Scheduling of the lytic event is determined in part by the "structure
      directed initiation" or sdi translational control region. Inductions of S, cloned
      under a variety of native and nonnative promoters but with native translational
      control, resulted in cell lysis at about 1000 molecules of holin per cell, and
      thus do not produce biochemically useful amounts of S protein. By utilizing a
      plasmid-based system with the T7 RNA polymerase promoter in tandem with a
      consensus ribosome binding site, Coomassie blue-detectable quantities of S
      protein were obtained upon induction, corresponding to an approximately 100-fold
      increase over the normal lethal level of holin. Characterization of this
      expression system is presented and discussed with respect to the current model of
      holin function.

PMID- 9572398
TI  - Similarities and differences between the effects of amino acids and nitroprusside
      on peritoneal permeability during CAPD.
AB  - OBJECTIVE: Intraperitoneal administration of amino acid based dialysis solutions
      affects the surface area available for diffusion, with almost no effect on the
      intrinsic permeability to macromolecules. Intraperitoneally administered
      nitroprusside affects the vascular surface area and the intrinsic permeability
      without effect on the peritoneal blood flow. In the present study, these
      differences were translated into different effects on the radii of the pores in
      the peritoneal membrane. METHODS: Effects of amino acid based dialysate and
      nitroprusside on peritoneal permeability characteristics were evaluated in
      standard peritoneal permeability analyses with L-arginine-containing amino acid
      dialysate (10 patients) or with 1.36% glucose dialysate with nitroprusside (10
      patients). In each patient a control experiment with 1.36% glucose was performed.
      Kinetic modeling was done to analyze the effects in terms of the pore theory.
      RESULTS: Both interventions increased the mass transfer area coefficients of low
      molecular weight solutes. This is in accordance with an increase in the
      unrestricted area over diffusion distance found with modeling. With amino acids
      almost no effect was found on the protein clearances; the increase in the large
      pore radius was only small. Nitroprusside induced a marked increase in protein
      clearances. This was in accordance with an evident increase in the average large
      pore radius. CONCLUSIONS: Amino acids affect the radii of the small pores and the
      large pores to the same extent. Nitroprusside influences especially the large
      pores. Both amino acids and nitroprusside are vasoactive, although the effects on
      the peritoneal microcirculation are different.

PMID- 9572397
TI  - High cell density induces vascular endothelial growth factor expression via
      protein tyrosine phosphorylation.
AB  - Expression of vascular endothelial growth factor (VEGF), an angiogenic factor and
      endothelial cell-specific mitogen, is induced by hypoxia in various cell lines as
      well as in solid tumors. In this study, we report that cell density has a
      profound effect on the expression of VEGF in human glioblastoma cells (U87) and
      human fibrosarcoma cells (HT1080), an effect that is independent of hypoxia.
      Northern blot analysis revealed that VEGF mRNA levels were four- to eightfold
      higher in cells seeded at high density compared to cells seeded at low density.
      This upregulation of VEGF message in response to seeding at high density was not
      seen with other mRNAs such as those for TGF-beta1 or GAPDH. Conditioned medium
      switch experiments between sparse and dense cells suggested that soluble
      factor(s) may not account for the observed changes in VEGF expression. Incubation
      with genistein, a protein tyrosine kinase inhibitor, for 3 h following seeding
      resulted in the reduction of the VEGF mRNA levels in highly confluent cultures
      but not in sparse cultures. To identify protein tyrosine kinases involved in the
      upregulation of the steady-state levels of VEGF mRNA in highly dense cultures, we
      analyzed the phosphorylation state of the c-src tyrosine kinase, in high versus
      low confluency cultures of U87 and HT1080 cells. Interestingly, an increased
      phosphorylation at Tyr416 of c-src was noted in high compared to low confluency,
      suggesting the activation of c-src in highly confluent cultures. Because
      extracellular signal-regulated kinases (ERKs) such as MAP kinase have been shown
      to be activated by extracellular stimuli and act downstream of c-src, we examined
      their possible involvement in this process. We found that the tyrosine
      phosphorylation level of MAP kinase is higher in dense compared to sparse
      cultures and, moreover, 6-thioguanine (6-TG), a potent inhibitor of ERKs, reduced
      VEGF mRNA levels in high but not low confluency. Furthermore, reintroduction of
      wild-type, but not mutant, von Hippel-Lindau (VHL) gene product in 786-O cells (a
      renal carcinoma cell line) specifically abrogated the induction of VEGF mRNA due
      to high cell density. Taken together, these data suggest that VEGF gene
      expression is regulated by cell density, and the protooncogene c-src and the
      tumor-suppressor VHL are modulators of this regulation.

PMID- 9572399
TI  - Dialysis hypersensitivity: a fading problem?
AB  - Allergic-type reactions experienced by patients on chronic hemodialysis are
      frequently reported in the literature, often related to compounds released during
      the hemodialysis sessions, in particular ethylene oxide (ETO). In these studies,
      dialysis patients seem to have higher values of IgE than those observed in a
      reference population. The aim of our work was to investigate IgE-related
      parameters of 126 dialysis patients in comparison with two control groups
      composed of healthy subjects and predialysis patients. IgE values were not
      significantly different in nonallergic dialysis patients, with a geometric mean
      (X) of 27.5 kU/l, when compared to healthy controls (X = 38 kU/l) and predialysis
      subjects (X = 40.7 kU/l). Higher values of IgE (X = 74.1 kU/l) were detected in
      allergic dialysis patients. However, only 3 patients, all without detectable
      antibodies against ETO, complained of anaphylactic symptoms during dialysis
      sessions in a 4-year surveillance period. At variance, 6 symptom-free patients
      carried IgE antibodies against ETO (range 0.7-15 kU/l), usually with high total
      IgE. Our results suggest a reduced frequency of hypersensitivity reactions during
      dialysis sessions. Furthermore, uremia does not alter IgE reactivity in the
      predialysis period or after long-term maintenance dialysis treatment.

PMID- 9572401
TI  - Use of the external iliac vein for temporary percutaneous access.

PMID- 9572400
TI  - Influence of plasma exchange on serum levels of cytokines and adhesion molecules
      in ANCA-positive renal vasculitis.
AB  - BACKGROUND: Increased serum levels of proinflammatory cytokines may contribute to
      the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive
      renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis
      not only by removing pathogenic autoantibodies, but also by lowering the serum
      levels of circulating cytokines. METHODS: Serum levels of IL-1beta, IL-1ra, IL-6,
      IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA
      positive renal vasculitis (5 patients with Wegener's granulomatosis, WG, and 5
      patients with microscopic polyangiitis, MPA) during the course of therapeutic PE.
      Cytokines and adhesion molecules were measured in samples of serum obtained at
      the beginning and at the end of the 1st, 3rd and 5th PE and in samples of
      filtrate obtained during the same PE. RESULTS: In comparison with controls,
      patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1
      before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased
      in patients with MPA, and the serum levels of all the cytokines and adhesion
      molecules measured in patients with WG were increased. At the end of the PE
      course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA
      patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led
      only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there
      was no change in serum levels of IL-1beta and IL-8, and the serum levels of IL
      1ra and IL-6 even increased at the end of a single PE, in spite of high levels of
      all cytokines and adhesion molecules in the plasma filtrate. CONCLUSION: Serum
      levels of soluble adhesion molecules decrease after PE, but serum levels of
      proinflammatory cytokines are not reduced even by a PE course. Removal of these
      substances by PE is obviously counteracted by their increased production,
      possibly further stimulated by the contact of blood with the synthetic membrane.
      The insufficient influence of PE on the elimination of proinflammatory cytokines
      may partially explain its limited effect in some patients with ANCA-positive
      renal vasculitis.

PMID- 9572402
TI  - Are spermatid injections of any clinical value? ROSNI and ROSI revisited. Round
      spermatid nucleus injection and round spermatid injection.

PMID- 9572403
TI  - The problems of spermatid microinjection in the human: the need for an accurate
      morphological approach and selective methods for viable and normal cells.

PMID- 9572404
TI  - ROSI, instructions for use: 1997 update. Round spermatid injection.

PMID- 9572405
TI  - Low day 3 luteinizing hormone values are predictive of reduced response to
      ovarian stimulation.
AB  - The aim of the present work was to evaluate whether low day 3 luteinizing hormone
      (LH) values in the presence of normal follicle stimulating hormone (FSH) are
      predictive of poor response to ovarian stimulation. Two groups of women
      undergoing ovarian stimulation and differing only in the day 3 LH concentration
      (<3 mIU/ml, study group, n=30; >3 mIU/ml, control group, n=45) were
      retrospectively analysed. Study group patients developed a lower oestradiol peak
      (703+/-388 versus 955+/-400 ng/ml; P = 0.005) and a lower number of follicles >15
      mm diameter at the time of human chorionic gonadotrophin (HCG) administration
      (2.6+/-1.3 versus 3.6+/-1.8; P=0.004) than the control group. Conversely, a
      similar ratio of oestradiol: follicles >15 mm diameter was observed (256+/-118
      versus 269+/-93; P=0.563). The number of follicles >10 mm at the time of HCG
      administration appeared to be lower in the study group, but this difference was
      not statistically significant (6+/-3.9 versus 7.8+/-4.3). Our data indicate that
      day 3 LH values <3 mIU/ml are predictive of poor response to ovarian stimulation.

PMID- 9572406
TI  - Is there a role for leptin in the endocrine and metabolic aberrations of
      polycystic ovary syndrome?
AB  - Immunoreactive serum leptin was analysed in 49 women with polycystic ovary
      syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and
      in 32 normally menstruating women with comparable age, BMI, physical activity and
      dietary habits. All women with PCOS had increased androgen concentrations and
      obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin
      sensitivity and a preferential accumulation of truncal-abdominal body fat.
      Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta
      cell activity were investigated in all women. Percentage body fat was calculated
      using gender-specific regression equations based on skinfold measurements. Serum
      leptin concentrations were higher in obese than in non-obese women (P < 0.001),
      but did not differ between the women with PCOS and controls, nor did they differ
      between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women
      with PCOS. Both groups showed strong correlations between serum leptin
      concentrations and percentage body fat, BMI, body fat distribution, fasting
      plasma insulin and C-peptide, early insulin secretion, the free androgen index
      (FAI), and the degree of insulin resistance. After correcting for percentage body
      fat, only the FAI in the women with PCOS remained significant (P < 0.05).
      However, in a multiple regression analysis with both percentage body fat and the
      FAI as independent variables, the FAI increased only minimally (2%) the explained
      variation in leptin concentrations. Thus, serum leptin concentrations are almost
      exclusively determined by the total amount of body fat, independent of its
      location, and do not confirm the hypothesis that leptin is involved in the
      development of the hormonal and metabolic abnormalities in the PCOS.

PMID- 9572407
TI  - Endocrino-metabolic features in women with polycystic ovary syndrome during
      pregnancy.
AB  - To elucidate the mechanism of metabolic adaptation of women with polycystic ovary
      syndrome (PCOS) during pregnancy, the endocrino-metabolic features of a group of
      PCOS patients with or without gestational diabetes were studied longitudinally
      during the three trimesters of gestation. Oral glucose tolerance test (OGTT, 100
      g) and hyperinsulinaemic-euglycaemic clamp were performed throughout the study.
      Plasma concentrations of insulin and glucose were determined by radioimmunoassay
      and glucose oxidase technique, respectively. Five of 13 PCOS patients developed
      gestational diabetes (GD) at the third trimester (PCOS-GD), while the other eight
      patients did not develop any alteration of glucose metabolism (PCOS-nGD). Both
      fasting glucose and insulin plasma concentrations did not change significantly
      during pregnancy and no difference was seen between the two groups. On the
      contrary PCOS-GD group early exhibited higher values of area under the curve
      (AUC) for glucose and insulin response to OGTT with respect to those found in
      PCOS-nGD group. This difference was already significant in the first gestational
      trimester. Moreover insulin sensitivity value (M) was significantly lower in the
      first trimester of gestation in PCOS-GD as compared with that found in PCOS-nGD
      group. However, as gestation proceeded, M value decreased in PCOS-nDG group and
      the difference from PCOS patients developing gestational diabetes was not
      sustained into the second and third trimesters. Both groups had similar body mass
      index values and AUC insulin increase from first to third trimester of gestation.
      It is concluded that early alteration of insulin sensitivity and secretion
      constitute specific risk factors in PCOS patients for the development of
      abnormalities of glucose tolerance.

PMID- 9572408
TI  - C-peptide and insulin, but not C19-steroids, support the predictive value of body
      mass index on leptin in serum of premenopausal women.
AB  - Hyperleptinaemia is known to be positively associated with obesity in females.
      Therefore, circulating leptin concentrations are predicted by body mass index
      (BMI). Additional effects of endogenous C19-steroids, sex hormone binding
      globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), C
      peptide and insulin on the predictive value of BMI on serum leptin were
      investigated in 56 hyperandrogenaemic and/or hyperinsulinaemic and/or obese
      premenopausal women. Serum concentrations (after an overnight 12 h fast) of
      leptin, total testosterone, free testosterone, SHBG, dehydroepiandrosterone
      sulphate (DHEAS), LH, FSH, and oestradiol as well as serum concentrations of C
      peptide and insulin prior to, and 1 h after, an oral 100 mg glucose load (1 h
      values) were determined by immunoassays. Subjects with regular menstrual cycles
      were studied in the mid-follicular phase while the remainder were studied at
      random. Nineteen normotestosteronaemic, normoinsulinaemic, lean and ovulatory
      volunteers served as controls; in order to determine the effect of different
      stages of the menstrual cylce, serum concentrations of leptin (and of oestradiol
      in 12 out of the 19 individuals) were determined at the preovulatory, the mid
      luteal and the following mid-follicular phase. Significant differences between
      the patients versus control were not found possibly because of the heterogeneity
      in the patient group. Multiple regression indicated a hyperbolic correlation
      between BMI and leptin concentrations. As expected, BMI was the major determinant
      responsible for >50% (R2=0.51) of the elevation of leptin concentrations. The
      combination of BMI with fasting C-peptide or fasting insulin enhanced the R2 up
      to 0.59. The multiple regression with two explaining parameters showed a
      significant regression coefficient for BMI at the 0.001 level, and for fasting C
      peptide and fasting insulin at the 0.01 level, which was as statistically
      significant as the combination of BMI with the 1 h values of C-peptide and of
      insulin. In contrast, total testosterone, free testosterone, SHBG, free
      testosterone/SHBG ratio, DHEAS and LH/FSH ratio had no effect. Similarly, models
      with more than two variables did not measurably improve the explained variation.
      In the control group, leptin concentrations were significantly higher in
      preovulatory and mid-luteal phases than the two mid-follicular phases (P < or =
      0.05) and must be considered when determining sampling time. In conclusion,
      hyperandrogenaemia does not have a predictive value on leptin concentrations in
      premenopausal subjects but hyperinsulinaemia exerts an effect independent of
      obesity that is the strongest predictor for elevation of leptin concentrations.
      Hyperinsulinaemia might contribute to the hyperbolic correlation of circulating
      leptin in obese patients.

PMID- 9572409
TI  - A bolus of recombinant human follicle stimulating hormone at midcycle induces
      periovulatory events following multiple follicular development in macaques.
AB  - The efficacy of follicle stimulating hormone (FSH) as an alternative to
      luteinizing hormone (LH)/human chorionic gonadotrophin (HCG) for the initiation
      of periovulatory events in primate follicles is unknown. A single bolus of 2500
      IU recombinant (r)-hFSH was compared to 1000 IU r-HCG for its ability to promote
      oocyte nuclear maturation and fertilization, granulosa cell luteinization and
      corpus luteum function following r-hFSH (60 IU/day) induction of multiple
      follicular development in rhesus monkeys. Following the r-hFSH bolus, bioactive
      luteinizing hormone concentrations were <3 ng/ml. Peak concentrations of serum
      FSH (1455+/-314 mIU/ml; mean+/-SEM) were attained 2-8 h after r-hFSH, and
      declined by 96 h. Bioactive HCG concentrations peaked between 2-8 h after r-HCG
      and remained > or = 100 ng/ml for >48 h, while immunoreactive FSH concentrations
      were at baseline. The proportion of oocytes resuming meiosis and undergoing in
      vitro fertilization (IVF) were comparable for r-hFSH (89%; 47+/-19%) and r-HCG
      (88%; 50+/-17%). In-vitro progesterone production and expression of progesterone
      receptors in granulosa cells did not differ between groups. Peak concentrations
      of serum progesterone in the luteal phase were similar, but were lower 6-9 days
      post-FSH relative to HCG. Thus, a bolus of r-hFSH was equivalent to r-HCG for the
      reinitiation of oocyte meiosis, fertilization and granulosa cell luteinization,
      but a midcycle FSH surge did not sustain normal luteal function in primates.

PMID- 9572410
TI  - Synchronization of endogenous and exogenous FSH stimuli in controlled ovarian
      hyperstimulation (COH).
AB  - We have previously observed that exogenous oestradiol can delay the intercycle
      increase in plasma follicle stimulating hormone (FSH). The increase in plasma FSH
      that follows discontinuation of exogenous oestradiol peaks after 3 days. We have
      now studied the possibility of using exogenous oestradiol to synchronize the
      increase in endogenous FSH with the onset of human menopausal gonadotrophin (HMG)
      treatment in controlled ovarian hyperstimulation (COH). A total of 30 women aged
      35.1+/-6.3 years (mean+/-SD) undergoing ovarian stimulation received 2 mg of
      oestradiol valerate twice daily starting on day 25 of the previous menstrual
      cycle until the first Tuesday following menses. Ovarian stimulation was initiated
      3 days later. On the last day of oestradiol treatment, plasma oestradiol, FSH and
      luteinizing hormone (LH) (mean+/-SEM) were 566+/-53 (pmol/l), 3.8+/-0.4 (IU/l)
      and 5.5+/-0.8 (IU/l) respectively. After 3 days, the FSH and LH (mean+/-SEM) had
      increased to 6.7+/-0.7 and 6.9+/-0.7 (IU/l) respectively while oestradiol
      decreased to 251+/-29 (pmol/l). The mean number (+/-SEM) of HMG ampoules used was
      25.1+/-2.7 and treatment lasted 11.3+/-0.9 days. Five women became pregnant for a
      pregnancy rate (ongoing) of 19 (15)%. If all women aged >40 years (six women who
      did not become pregnant) were excluded from analysis the pregnancy rate (ongoing)
      was 24 (19%). These results indicate that exogenous oestradiol can safely be used
      for the synchronization of endogenous and exogenous FSH stimuli in COH. This
      approach provides the practical advantage of permitting an advanced timing of the
      onset of COH treatments when gonadotrophin-releasing hormone (GnRH) agonists are
      not used, which improves treatment convenience for patients and team members
      alike. Further development of this model may enable control of the onset of
      natural cycles which may find practical applications for timing assisted
      reproductive techniques (intrauterine insemination or in-vitro fertilization) in
      the natural cycle.

PMID- 9572411
TI  - The use of a 100 IU starting dose of recombinant follicle stimulating hormone
      (Puregon) in in-vitro fertilization.

PMID- 9572412
TI  - The impact of insulin resistance on the outcome of ovulation induction with low
      dose follicle stimulating hormone in women with polycystic ovary syndrome.
AB  - In this study we examined the possible correlation between insulin metabolism and
      outcome of gonadotrophin stimulation in infertile clomiphene citrate resistant
      women with polycystic ovary syndrome (PCOS). The patient group comprised 42 women
      who were entered into the study in a consecutive fashion. Following performance
      of the CIGMA (continuous infusion of glucose with model assessment) test, 17
      women were classified as insulin resistant and 25 women as non-insulin resistant.
      Each woman received up to two cycles of low-dose follicle stimulating hormone
      (FSH) stimulation starting with 75 IU of FSH for 1 week, giving a total of 70
      cycles performed. The insulin resistant PCOS women required more gonadotrophin
      and a longer time to achieve follicular maturation. By multiple regression
      gonadotrophin consumption correlated best with CIGMA value but not with fasting
      insulin concentration or body mass index. In the insulin resistant PCOS women 10
      out of 29 cycles were cancelled due to a multifollicular response, while only one
      of 41 cycles was cancelled in the non-insulin resistant PCOS women. Although
      ovulation rate in completed cycles was similar between the groups, the conception
      rate was significantly better in the non-insulin resistant PCOS women. In
      conclusion, in PCOS women insulin resistance seems to be an unfavourable
      condition resulting in an elevated cancellation rate and a low conception rate
      following low-dose FSH stimulation.

PMID- 9572413
TI  - Symptomatic unilateral pleural effusion as a presentation of ovarian
      hyperstimulation syndrome.
AB  - Isolated acute unilateral pleural effusion has twice been reported as the only
      symptom of ovarian hyperstimulation syndrome (Kingsland et al, 1989; Jewelewicz
      and Vande Wiele, 1975). The pathogenesis of this disorder is not fully understood
      and the presence of an isolated pleural effusion lends support to the role of
      systemic factors rather than purely the transudation of fluid from grossly
      enlarged ovaries in the progression of this disease. This article describes a
      second case of an isolated pleural effusion following in-vitro fertilization and
      embryo transfer.

PMID- 9572414
TI  - High dose gonadotrophin-releasing hormone antagonist (ganirelix) may prevent
      ovarian hyperstimulation syndrome caused by ovarian stimulation for in-vitro
      fertilization.
AB  - This case report describes the first attempt to treat imminent ovarian
      hyperstimulation syndrome (OHSS) by using a gonadotrophin-releasing hormone
      (GnRH) antagonist. A 33 year old, normo-ovulatory woman undergoing in-vitro
      fertilization received daily subcutaneous injections of 150 IU of recombinant
      follicle-stimulating hormone (recFSH) from cycle day 2, together with GnRH
      antagonist (ganirelix) 0.125 mg from cycle day 7 onwards. On cycle day 10 the
      patient was found to have a serum oestradiol concentration of 16 500 pmol/l and,
      on ultrasound examination, four preovulatory (>16 mm) and nine intermediate sized
      (10-16 mm) follicles. RecFSH injections were discontinued, human chorionic
      gonadotrophin (HCG) withheld, whereas the ganirelix dose was increased to 2 mg/d.
      This regimen led to a rapid decrease in serum oestradiol concentrations and the
      decrease in ovarian size on ultrasound. Since GnRH antagonists will become
      clinically available for in-vitro fertilization programmes in the near future
      this suggested regimen might have a role in preventing severe OHSS.

PMID- 9572415
TI  - Chromosome abnormalities in 447 couples undergoing intracytoplasmic sperm
      injection--prevalence, types, sex distribution and reproductive relevance.
AB  - Chromosomal abnormalities are thought to be a major contributor to the genetic
      risks of infertility treatment by intracytoplasmic sperm injection (ICSI). Apart
      from abnormalities arising de novo, abnormal karyotypes in pregnancies conceived
      through assisted reproductive technology may be directly derived from
      predisposing parental aberrations. In a prospective study we have analysed the
      chromosomes of 868 male and female patients prior to planned ICSI treatment. A
      total of 33 aberrant karyotypes was diagnosed, corresponding to an abnormality
      rate of 7.6% per couple or 3.8% per individual studied. Even though male factor
      infertility was twice as common as female factor infertility in this cohort, 24
      of the chromosomal abnormalities were found among the women. Low-level mosaicism
      for numerical sex chromosome anomalies was diagnosed in 20 individuals, and one
      patient had the triple X karyotype. With respect to structural chromosomal
      anomalies, we found six reciprocal and three Robertsonian translocations, two
      paracentric inversions and one marker chromosome. Many of the aberrations that we
      diagnosed could be classified as carrying only a small to moderate reproductive
      risk. Given the high rate of abnormal karyotypes among the female subjects, we
      suggest that not only the males, but both partners should be routinely karyotyped
      prior to ICSI.

PMID- 9572416
TI  - Chromosome studies in first polar bodies from hamster and human oocytes.
AB  - Most studies on preconception diagnosis published so far have used polymerase
      chain reaction (PCR) analysis to identify single gene defects. Although
      fluorescent DNA probes have been used to obtain a partial cytogenetic diagnosis
      of aneuploidies in first polar bodies without defined chromosome structures, the
      analysis of structural chromosome anomalies in the interphase nucleus is not
      adequate. We describe a procedure to obtain first polar body chromosome
      complements from hamster and human oocytes. In 63.6% (105 of 165) of hamster
      first polar bodies the chromosome complement showed a defined chromosome
      morphology and in 94.1% (16 of 17) of human oocytes fixed after follicular
      puncture it was possible to obtain high quality, well spread chromosome
      complements. First polar body chromosomes are fuzzy and shorter than oocyte
      chromosomes, but fluorescent in-situ hybridization results obtained in human
      first polar bodies clearly show that it is possible to detect whole chromosomes,
      centromeres and unique sequences, including the terminal regions of small
      chromosomes. This suggests that in fresh oocytes, DNA loss resulting from
      apoptotic chromosome fragmentation has not yet occurred. Using the procedure
      described, first polar bodies could be used to analyse the meiotic segregation of
      maternal structural abnormalities and to detect numerical chromosome anomalies in
      humans.

PMID- 9572417
TI  - Appendectomy under local anaesthesia following conscious pain mapping with
      microlaparoscopy.
AB  - The appendix is an under-appreciated source of chronic pelvic pain. Laparoscopic
      evaluation of the appendix is limited without intra-operative patient feedback on
      the presence and absence of pain. New techniques using local anaesthesia with
      conscious sedation have enabled us to perform operative laparoscopic surgery
      while the patient is awake. We report the first two cases of microlaparoscopic
      appendectomies performed under local anaesthesia with conscious sedation
      following diagnosis obtained during conscious pain mapping.

PMID- 9572418
TI  - Seminal plasma alpha-glucosidase activity and male infertility.
AB  - Measurement of alpha-glucosidase (alpha-GLUC) activity by means of a simple
      colorimetric test using a commercial kit (EpiScreen; FertiPro, Lotenhulle,
      Belgium) yielded results that were strongly correlated with the values obtained
      for the neutral iso-enzyme measured by a fluorimetric reference method (r=0.85,
      P=0.003, n=13). The former method was characterized by a low intra- and inter
      coefficient of variation (6.6 and 4.3% respectively). Vasectomized men with
      azoospermia (n=27) had a significantly lower alpha-GLUC activity in semen than
      vasectomized men with residual spermatozoa present (n=11, P < 0.01) and men with
      azoospermia of primary testicular origin (n=33, P < 0.01). Receiver operating
      curve (ROC) analysis showed alpha-GLUC measurement to be reasonably accurate in
      differentiation between cases with obstructive versus testicular azoospermia at
      criterion value 13.5 U/l (sensitivity=82%, specificity= 70%). In cases with
      spermatozoa present, alpha-GLUC activity and output per ejaculate were positively
      correlated with sperm concentration (r=0.53 and 0.38, n=472), linear velocity
      (r=0.35 and 0.30, n=224), curvilinear velocity (r=0.32 and r=0.29, n=224), semen
      adenosine triphosphate (r=0.35 and 0.26, n=64), the concentration of 5alpha
      dihydrotestosterone (r=0.31 and 0.29, n=74), and gamma-glutamyltransferase
      activity (r=0.62 and 0.32, n=275) in seminal plasma. The activity of alpha-GLUC
      was inversely correlated with ROS generation after 12-myristate, 13-acetate
      phorbol ester stimulation (r=-0.27, n=104), and both alpha-GLUC activity and
      total output were inversely correlated with the concentration of peroxidase
      positive white blood cells among samples with > or =1x10(6)/ml of these cells (r=
      0.30 and -0.19, n=165). It is concluded that simple photometric measurement of
      alpha-GLUC activity in seminal plasma reflects the functional state of the
      epididymis and may be helpful for the differential diagnosis of certain cases
      with azoospermia.

PMID- 9572419
TI  - Recombinant human follicle stimulating hormone for treatment of male idiopathic
      infertility: a randomized, double-blind, placebo-controlled, clinical trial.
AB  - To examine the role of recombinant human follicle stimulating hormone (rhFSH) in
      male idiopathic infertility a randomized, double-blind, placebo-controlled study
      was performed. Of 211 patients screened, 67 were finally included. After two pre
      examinations, patients were randomized and treated for 12 weeks, either with 150
      IU rhFSH or with placebo. Examinations (physical examination, scrotal
      ultrasonography, semen analysis, hormone measurements, and in 31 patients
      electron microscopy (EM) of spermatozoa were performed 6 and 12 weeks after
      treatment initiation and 6 and 12 weeks after completion of treatment.
      Pregnancies were recorded for a further 3 months after the last examination. Of
      the 67 patients included in the study, 34 treated and 31 placebo patients could
      be analysed. In the treated group, FSH was elevated compared to baseline values
      (P < 0.001). At the end of treatment testicular volume in the treated group was
      increased compared to placebo (P < 0.05) and baseline (P < 0.001). Apart from an
      increase in sperm motility (P < 0.05) in the placebo group and in sperm DNA
      condensation (P < 0.001) in the treated group no significant changes were
      observed in semen parameters. Two spontaneous pregnancies in partners of men in
      the treated group and none in the placebo group occurred. However, two
      pregnancies occurred in partners of men in the placebo group induced by
      intrauterine insemination or intracytoplasmic sperm injection. In conclusion, at
      the chosen dose and duration, rhFSH did not lead to an improvement of
      conventional or EM sperm parameters nor to an increase in pregnancy rates.
      However, the increased testicular volume and sperm DNA condensation give reason
      for further investigations.

PMID- 9572420
TI  - Ultrastructural localization of angiotensin-converting enzyme in ejaculated human
      spermatozoa.
AB  - Angiotensin-converting enzyme (ACE) is known to be released from human
      spermatozoa during capacitation. However, it has not yet been localized
      ultrastructurally in ejaculated sperm cells. Therefore, the purpose of the
      present study was to demonstrate the location of ACE by means of immunoelectron
      microscopy and direct immunofluorescence. In addition, ACE activity of
      spermatozoa was correlated with standard semen parameters. The activity of
      angiotensin-converting enzyme was measured in spermatozoa from 115 donors and
      patients attending the andrological outpatient department. Progressive motility
      was negatively correlated with sperm ACE activity (Spearman rank correlation r=
      0.364, P < 0.0001), whereas no statistically significant correlations with sperm
      concentration, total motility and morphology were observed. Immunoelectron
      microscopy demonstrated that ACE is mainly located at the plasma membrane of the
      acrosomal region, equatorial segment, postacrosomal region and midpiece. In
      contrast, only weak ACE-like immunoreactivity was found at the flagellum. In
      cases of cells with missing plasma membranes ACE seems also to be located at the
      surface of the outer acrosomal membrane. By means of immunohistochemical methods,
      different patterns of ACE-like immunofluorescence were observed: (i) fluorescence
      of the acrosome or the entire sperm head, midpiece and flagellum; (ii)
      fluorescence of the postacrosomal region, midpiece and flagellum; (iii) bright
      fluorescence of the equatorial segment with less intensive labelling of the
      postacrosomal region and flagellum. Induction of the acrosome reaction by calcium
      ionophore A23187 resulted in an increase of spermatozoa with weak acrosomal
      fluorescence, indicating loss of the plasma membrane.

PMID- 9572421
TI  - Factors influencing human sperm kinematic measurements by the Celltrak computer
      assisted sperm analysis system.
AB  - This study examines the effect of varying several factors, both extrinsic and
      technology-dependent, on the reconstruction of human sperm trajectories and the
      derived kinematic measurements using videotapes and the Motion Analysis
      Celltrak/S instrument. In semen samples from normal healthy men, curvilinear
      (VCL) and straight line velocities (VSL) were found to increase 1.5-fold, and
      linearity (LIN) of trajectories and amplitude of lateral head displacement (ALH)
      increased 1.25-fold when the temperature of analysis was raised from 24 to 37
      degrees C. Only VCL and VSL were found to increase significantly between 24 and
      37 degrees C for sperm samples selected by Percoll gradient and incubated in a
      capacitating medium. An analysis chamber of 20 microm depth was found to be
      adequate for seminal sperm samples while for Percoll-selected sperm samples the
      analysis in a 50 microm depth provided the highest proportions of spermatozoa
      with the highest VCL and the largest ALH. The grey level detection threshold
      required careful adjustment: using a threshold lower than the optimal threshold
      produced spurious sperm trajectories for seminal sperm samples and rejected some
      trajectories for Percoll-selected sperm samples. Definition of the appropriate
      frame rate and maximum burst speed was critical for valid trajectory
      reconstruction and therefore adequate derived kinematic measurements. Optimal
      values of these parameters were found to be 30 Hz and 400 microm/s for seminal
      spermatozoa and 60 Hz and 700 microm/s for selected spermatozoa. The optimal
      values of 'ALH path-smoothing factor' used to calculate average path and ALH were
      5-10 points for seminal spermatozoa analysed at 30 Hz and 15-20 points for
      selected spermatozoa analysed at 60 Hz. We propose a set of standard conditions
      for reliable kinematic analysis of human spermatozoa using the Celltrak/S system.

PMID- 9572422
TI  - Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of
      obstructive azoospermia.
AB  - Male genital tract obstructions may result from infections, previous inguinal and
      scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens
      (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In
      other cases and in cases of failed surgical intervention, the patient can be
      treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA)
      or testicular sperm extraction (TESE) and intracytoplasmic sperm injection
      (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia
      in 24 couples. The aetiology of the obstruction was failed microsurgery in 11
      patients, CBAVD in nine and genital infections in four. Sperm retrieval was
      accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases.
      TESE was only applied when PESA failed to produce enough spermatozoa for
      simultaneous ICSI. In six patients, the ICSI procedure was performed with
      cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred
      in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of
      procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing
      pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early
      after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards
      syndrome). The other nine pregnancies resulted in the live birth of 10 children,
      without any congenital abnormalities. Epididymal and testicular retrieved
      spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and
      resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI
      procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo
      transfer.

PMID- 9572423
TI  - The predictive value of the zona-free hamster egg penetration test in relation to
      in-vitro fertilization at various insemination concentrations.
AB  - The aim of the study was to evaluate the predictive value of the zona-free
      hamster egg penetration test (ZHEPT) for success in in-vitro fertilization (IVF)
      at various insemination concentrations ranging between 0.1 and >0.6 x 10(6)/ml.
      The ZHEPT was assessed using sperm samples from 87 couples undergoing IVF
      treatment. A similar test was simultaneously performed on the same semen sample
      following ionophore induction of the acrosome reaction (ZHEPTii test). Both the
      tests were poorly correlated with the fertilization rate of IVF at all the
      insemination concentrations except at >0.6 x 10(6)/ml, when there was good
      correlation between the ZHEPTii test and the fertilization rate. Following
      exclusion of two cases with an oocyte problem, further statistical analysis
      revealed that both the ZHEPT and ZHEPTii tests were poorly correlated with
      fertilization rate in IVF in this treatment group. This study suggests that the
      ZHEPT (with and without ionophore induction of the acrosome reaction) has a poor
      predictive value for the success of fertilization in IVF treatment at any
      insemination concentration.

PMID- 9572424
TI  - Repetitive ejaculation before intracytoplasmic sperm injection in patients with
      absolute immotile spermatozoa.
AB  - Cases with absolute immotile sperm syndrome are rare, and include the genetic
      defect of immotile cilia syndrome with the absence of dynein arms in the
      flagellum. We attempted to increase the percentage of viable spermatozoa to
      improve the outcome of intracytoplasmic sperm injection (ICSI). Three couples in
      whom repeated analysis of the male partners indicated 100% sperm immotility
      underwent an in-vitro fertilization (IVF) procedure in which ICSI was performed.
      On their first ICSI cycle the males produced a single ejaculation while in their
      successive ICSI cycles they were requested to repeatedly ejaculate (two to four
      times) and only the last ejaculation was used. The eosin-Y test was performed on
      each used sample. Following their first treatment, one couple had one repeated
      treatment cycle, another had two and the third couple had three repeated
      treatment cycles. The mean percentages of viable spermatozoa were 41+/-7.4 and
      71+/-6.9% in the first and repeated cycles respectively (P < 0.01; t-test). Of
      the 39 oocytes injected in the first ICSI cycles only one (3%) was normally
      fertilized (2PN) compared with 41 (48%) of the 85 oocytes injected in the
      repeated ICSI cycles. One (3%) embryo in the first and 35 (41%) embryos in the
      repeated ICSI cycles respectively were obtained (P < 0.001), enabling their
      replacement into the uterine cavity in all the repeated cycles. One woman (in a
      repeated cycle) conceived a twin pregnancy and delivered two healthy babies. The
      use of spermatozoa from repeated ejaculation is recommended in men with
      absolutely immotile spermatozoa so as to obtain significantly better viability
      and fertilizing capacity.

PMID- 9572425
TI  - Short-term in-vitro culture and cryopreservation of spermatogenic cells used for
      human in-vitro conception.
AB  - Testicular cell suspensions were prepared from obstructive and non-obstructive
      azoospermic men and were cultured in vitro for 96 h as (i) mixed cell populations
      and (ii) isolated homogeneous populations of primary spermatocytes, round
      spermatids and elongating spermatids. The cells lost their viability gradually
      during the first 24 h period. By 72 h almost 90% of the cells were non-viable.
      Isolated pure fractions showed better viability at each time interval (P <
      0.0005). Throughout the culture period primary spermatocytes, elongating
      spermatids and other non-spermatogenic cells showed no change in their
      morphology, but almost 22% of round spermatids showed growth of flagella. Most of
      the round spermatids developed their flagella during the first 4-8 h period of
      culture. Isolated pure round spermatids showed better flagellar growth compared
      with mixed cell suspensions (P < 0.0005). The spermatogenic cells were
      successfully cryopreserved. However, when mixed spermatogenic cell suspensions
      were cryopreserved, more cells lost their viability compared with when isolated
      pure fractions were cryopreserved (P < 0.0005).

PMID- 9572426
TI  - Isolation, purification and assessment of viability of spermatogenic cells from
      testicular biopsies of azoospermic men.
AB  - The success of spermatid microinjection has generated many concerns. In
      particular, there is a lack of appropriate methodology for the isolation of large
      homogeneous populations of spermatids, with minimum loss of viability, from the
      testicular tissue of azoospermic men. Here we have compared two different
      isolation methods -- velocity sedimentation under unit gravity (VSUG) combined
      with discontinuous Percoll centrifugation (DPC), and separation with fluorescent
      activated cell sorter (FACS) using light in the visible range -- to determine the
      most suitable method for the isolation of spermatids. Total mixed cell count/gram
      of testicular parenchyma was significantly higher in obstructive azoospermic men
      compared with non-obstructive azoospermic men (P < 0.001). The results of the
      comparison showed that in obstructive azoospermic patients the difference in the
      yields of primary spermatocytes produced by the two techniques was not
      significant, but for round and elongating spermatids the FACS separation proved
      to be the better method (P < 0.001). Similarly, in non-obstructive azoospermic
      patients, FACS separation proved to be superior, giving increased yields of
      primary spermatocytes and round and elongating spermatids compared with VSUG
      combined with DPC method (P < 0.001). More than 99 % of the separated cells
      retained their viability after FACS separation. As large homogeneous populations
      of viable spermatids can be separated with FACS in a relatively short period of
      time, FACS separation is the most suitable method for the isolation of spermatids
      from testicular biopsy tissue.

PMID- 9572427
TI  - The efficacy of local anaesthesia for percutaneous epididymal sperm aspiration
      and testicular sperm aspiration.
AB  - A total of 37 percutaneous epididymal sperm aspiration (PESA) and/or testicular
      sperm aspiration (TESA) procedures were performed under local anaesthesia (LA) on
      34 men between June and November 1996. Local anaesthesia was achieved by
      injecting 10 ml of 1% lignocaine solution along the sides of the vas deferens
      near the external inguinal ring (spermatic cord block). Sperm retrieval was
      successful in 92% of the procedures. Of the 37 procedures, in 29 the patients
      felt either no pain or mild discomfort while in six they experienced moderate but
      tolerable pain. Analgesia was incomplete in two procedures and was supplemented
      with i.v. sedation. Vasovagal reflex in two procedures was reversed by i.v.
      atropine. In 24 procedures patients felt relaxed, whilst in 13 they felt anxious.
      In 32 procedures the patients expressed overall satisfaction. If the procedure
      was to be repeated, after 29 procedures the patients requested LA again, while
      after four procedures they preferred i.v. sedation and after four were undecided.
      LA is adequate for PESA and TESA in a large proportion of patients. Prior
      discussion of LA technique with the patient is necessary. Back-up facilities for
      i.v. sedation and atropine should be available.

PMID- 9572428
TI  - Serum vascular endothelial growth factor concentrations and ovarian stromal blood
      flow are increased in women with polycystic ovaries.
AB  - The aim of this study was to determine basal serum vascular endothelial growth
      factor (VEGF) concentrations and Doppler blood flow changes within the ovarian
      stroma of women with polycystic ovaries (PCO) and women with normal ovaries.
      Pulsed and colour Doppler blood flows within the ovarian stroma were recorded,
      and serum VEGF concentrations measured, in the early follicular phase (days 2-3
      of a menstrual cycle) in 60 women undergoing ovarian stimulation for in-vitro
      fertilization. 36 women had normal ovaries, 14 women had PCO as seen on pelvic
      ultrasound examination and 10 had polycystic ovarian syndrome (PCOS). Mean+/-SD
      serum VEGF concentrations were significantly higher (P < 0.001) in women with PCO
      and PCOS (3.4+/-0.7 and 3.2+/-0.66 ng/ml respectively) compared with women with
      normal ovaries (2.3+/-0.5 ng/ml). Mean peak systolic blood flow velocity (PSV)
      and time-averaged maximum flow velocity (TAMXV) were significantly higher (P <
      0.001) in women with PCO and PCOS compared with women with normal ovaries. The
      mean PSV were 15+/-4 and 16+/-4 cm/s in women with PCO and PCOS respectively,
      compared with 9+/-2 cm/s in women with normal ovaries. The TAMXV were 9+/-3 and
      11+/-3 cm/s in women with PCO and PCOS respectively compared with women with
      normal ovaries (5.8+/-1.5 cm/s). Serum VEGF concentrations were positively
      correlated with PSV (r=0.44, P=0.001) and TAMXV (r=0.45, P < 0.000) in all three
      groups of women. Higher serum concentrations of VEGF in women with PCO and PCOS
      may relate to the increased vascularity that underlies the increased blood flow
      demonstrated by Doppler blood flow velocity measurements in these women. The
      results may explain the higher risk of ovarian hyperstimulation syndrome in
      programmes of ovarian stimulation in patients with PCO compared with those with
      normal ovaries.

PMID- 9572429
TI  - Increase in transforming growth factor beta1 in ovarian follicular fluid
      following ovarian stimulation and in-vitro fertilization correlates to pregnancy.
AB  - We have analysed the content of the growth and differentiation regulating
      peptide, transforming growth factor beta1 (TGFbeta1), in follicular fluid from
      patients undergoing in-vitro fertilization (IVF), and correlated concentrations
      of TGFbeta1 with the outcome of the IVF treatment and the concentrations of
      17beta oestradiol in serum at ovum retrieval. A total of 88 women with
      infertility of >3 years duration and age <38 years participated in the study.
      During IVF treatment, follicular fluid and matched serum samples were collected
      at ovum retrieval and analysed for TGFbeta1, oestradiol, progesterone, follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) using radioimmunoassay and
      enzyme-linked immunosorbent assay. We found that the TGFbeta1 content in the
      follicular fluid at the time of oocyte retrieval correlated positively with
      subsequent pregnancy. In 29 women who became pregnant following IVF, follicular
      fluid TGFbeta1 values were significantly higher (P=0.005) than in 59 women where
      IVF was unsuccessful. In the pregnant group, TGFbeta1 values correlated
      positively with oestradiol at ovum retrieval. TGFbeta1 also correlated positively
      with the number of fertilized oocytes. TGFbeta1 may thus be important for
      successful human pre-embryo development, contribute to successful embryo
      implantation and development and may be necessary for the establishment of
      pregnancy.

PMID- 9572430
TI  - Fertility results after ovarian transposition for pelvic malignancies treated by
      external irradiation or brachytherapy.
AB  - The aim of this study was to assess the fertility outcome after ovarian
      transposition with uterine conservation and pelvic irradiation therapy for pelvic
      cancer. A total of 37 consecutive cases were reviewed. Of these, 27 patients were
      treated for a clear cell adenocarcinoma of the vagina and/or the cervix (group
      1), nine for an ovarian pure dysgerminoma and one for a para-uterine soft tissue
      sarcoma (group 2). The pregnancy rate was 15% (4/27) in group 1 and 80% (8/10) in
      group 2 (P=0.01). A total of 18 pregnancies was observed in 12 patients. Of
      these, 16 pregnancies were obtained spontaneously and two after in-vitro
      fertilization. Of the spontaneous pregnancies, 12 (75%) were observed with
      ovaries still in the abdominal cavity (not repositioned). These results show that
      the prognosis for fertility is excellent after ovarian transposition and
      irradiation in patients with morphologically normal genital tracts (group 2). The
      prognosis is not as good for patients treated for a clear cell adenocarcinoma of
      the vagina and/or the cervix who may have morphological and/ or functional
      anomalies of the genital tract, following exposure to diethylstilboestrol and
      brachytherapy (group 1). Furthermore, these results show that repositioning of
      the ovary is not essential to achieve pregnancy.

PMID- 9572432
TI  - Factors influencing sperm-zona pellucida binding in vitro using the intact zona
      model.
AB  - The zona pellucida binding assay assesses the ability of spermatozoa to bind to
      the zona pellucida. The present study investigated the influence of: (i) prior
      oocyte exposure to spermatozoa on subsequent sperm-zona pellucida binding in
      vitro; and (ii) cryopreservation of oocytes. Only oocytes obtained from fertile
      donors were used and the binding capacity of non-inseminated, cryopreserved
      oocytes was compared with both inseminated/unfertilized, cryopreserved oocytes
      and inseminated/unfertilized, non-cryopreserved oocytes recovered from in-vitro
      fertilization cultures on sperm-zona pellucida binding using an intact zona
      model. There was no statistically significant difference in sperm-zona binding
      between non-inseminated, cryopreserved oocytes (range 9.6-23.2),
      inseminated/unfertilized, cryopreserved oocytes (range 15.0-16.0) and
      inseminated/ unfertilized, non-cryopreserved oocytes (range 3.3-23.0). The
      coefficient of variation for sperm binding to all oocyte groups was very large
      (range 37-121%). We conclude that neither prior exposure of human oocytes to
      human spermatozoa nor cryopreservation of human oocytes influences the subsequent
      binding of a different population of spermatozoa to the zona pellucida. However,
      large oocyte-to-oocyte variation of sperm-zona binding may diminish the
      usefulness of this assay in clinical practice and as a research tool.

PMID- 9572431
TI  - Epidermal growth factor combined with recombinant human chorionic gonadotrophin
      improves meiotic progression in mouse follicle-enclosed oocyte culture.
AB  - Using a mouse early preantral follicle culture system, mature full grown oocytes,
      arrested in prophase I of meiosis, were produced after 12 days using a
      recombinant gonadotrophin-supplemented medium. This culture medium does not mimic
      the normal extracellular environment of the oocyte and might therefore modify
      meiotic regulation and more particularly progression to metaphase II (MII). The
      aim of this study was to optimize the treatment using recombinant stimulatory
      ligands which were known to induce germinal vesicle breakdown (GVBD) and
      completion of meiosis I, metaphase II (MII), namely recombinant follicle
      stimulating hormone (r-FSH), chorionic gonadotrophin (r-HCG) and epidermal growth
      factor (EGF). Full-grown intrafollicular oocytes could not resume meiosis when
      the 'ovulatory' stimulus was r-FSH, used at a 100 times higher dose than during
      culture. r-FSH did not increase progesterone production. When 1.5 IU/ml r-HCG was
      used as meiotic trigger, germinal vesicle breakdown was obtained in 95% of the
      oocytes 64% of which extruded a first polar body. r-HCG induced a dramatic
      increase in progesterone production. When EGF was administered as sole stimulus
      on day 12 to the attached follicle-enclosed oocytes, only doses > or =5 ng/ml
      could cause GVBD, although less effectively than r-HCG (45 versus 95%; P <
      0.0001). Oocytes undergoing GVBD by the EGF pulse reached metaphase II at a rate
      of 54% (not significant versus r-HCG). EGF did not stimulate progesterone
      production. Addition of increasing doses of EGF (0.5; 5; 10; 50 ng/ml) to r-HCG
      did not increase the GVBD-rate, but EGF doses >5 ng/ml improved MI to MII
      transition (P=0.027), thereby improving the final yield of MII oocytes by 12.5%.
      These data show that up to a dose of 50 ng/ml, EGF on its own could only override
      the somatic inhibitory stimuli in less than half of the cultured follicles.
      However, in addition to HCG, EGF (25 ng/ml) had a stimulatory effect on
      completing the first meiotic division. It was concluded that, under the present
      culture conditions, EGF in combination with HCG provided optimal nuclear
      maturation.

PMID- 9572433
TI  - The rate of development and time of transfer play different roles in influencing
      the viability of human blastocysts.
AB  - Improved embryo culture protocols now render more feasible the possibility of
      obtaining human blastocysts after in-vitro fertilization. In this study we
      present: (i) results of blastocyst development from supernumerary embryos after
      co-culture on green monkey kidney epithelial cells and (ii) pregnancy rates after
      transfer of frozen blastocysts. In addition, we have examined the influence of
      the day of blastocyst freezing and the day of transfer after the luteinizing
      hormone (LH) peak on pregnancy and implantation rates. Of 423 supernumerary
      embryos, 200 developed to the blastocyst stage (47.3%). By days 5 and 6, 67% of
      the blastocysts had reached the blastocyst stage, and were frozen, compared to
      28.5% by day 7. When we compared the cases where only blastocysts frozen on days
      5 and 6 were transferred compared to those frozen and transferred on or after day
      7 the pregnancy rates were 7/18 (38.9%) and 1/16 (6.2%) respectively. In
      contrast, when we examined the influence of the day of transfer we found that
      pregnancies were established from day 5 up to day 9 post LH peak. Based on these
      results, we suggest that every attempt should be made to increase the development
      rate of supernumerary embryos to the blastocyst stage, as it appears that the
      quality of blastocysts transferred, as shown in this study by rate of
      development, plays a more crucial role than the timing of transfer.

PMID- 9572434
TI  - Human gamete fusion can bypass beta1 integrin requirement.
AB  - Since alpha6beta1 integrin has been shown to function as a sperm adhesion
      receptor in the mouse, we investigated the potential role of beta1 integrin in
      the gamete fusion process in humans. The expression of beta1 integrin was
      morphologically analysed by indirect immunofluorescence and confocal microscopy.
      A homogeneous and intense staining was detected at the plasma membrane, and in
      some subcortical vesicles of germinal vesicle stage oocytes (GV). Beta1 almost
      disappeared from oolemma and cytoplasm of metaphase I (MI) oocytes, but was re
      expressed as asymmetrical patches at the plasma membrane of metaphase II stage
      oocytes (MII). A functional fusion assay based on Hoechst or calcein-AM dye
      transfer from one gamete to the other showed that maturing oocytes were able to
      fuse with an increasing number of spermatozoa (11-22 from GV to MII
      respectively), and that fused spermatozoa co-localized with beta1 integrin
      patches. Human gamete fusion was only partially inhibited either by RGD
      containing peptide (GRGDTP), or by blocking anti-human beta1 integrin monoclonal
      antibody (DE9), with a maximum of 50% inhibition. Despite the combined addition
      of GRGDTP and blocking mouse anti-human beta1 integrin DE9 in the assay, a
      complete inhibition of fusion could not be achieved. A mouse polyclonal antibody
      raised against human oocyte membranes was more potent in inhibiting the fusion.
      Since beta1 integrin expression at the plasma membrane was not correlated to
      oocyte fusibility, and since it was only partially inhibited by DE9 and/or RGD
      peptide, we suggest that human gamete fusion can bypass the beta1 requirement.
      Beta1 integrin certainly participates in human gamete fusion by acting in co
      operation with multiple integrin/disintegrin couples or another cofactor, not yet
      identified.

PMID- 9572435
TI  - The effect of follicle stimulating hormone and epidermal growth factor on the
      developmental capacity of in-vitro matured mouse oocytes.
AB  - This study investigates the effects of follicle stimulating hormone (FSH) or
      epidermal growth factor (EGF) on the development of mouse oocytes matured in
      vitro. The data show that addition of FSH or EGF does not significantly increase
      the proportion of oocytes maturing to metaphase II but does increase the ability
      of these oocytes to cleave to the 2-cell stage after fertilization. After
      transfer of 2-cell embryos to pseudopregnant recipients, 64-78% of the embryos
      implanted, which was significantly reduced compared to embryos from in-vivo
      matured controls (89%). Fewer fetuses at day 14 of gestation were produced from
      embryos derived from oocytes matured in basal conditions (26%), or in the
      presence of EGF (32%), compared to oocytes matured in vivo (64%) or in the
      presence of FSH (58%). Examination of polar bodies and pronuclei of oocytes
      matured in vitro suggests that an increase in the rate of triploidy may be partly
      responsible for the increased fetal loss after maturation in the absence of FSH.
      This study shows that the fertilization rate after in-vitro maturation can be
      improved by FSH and EGF and that subsequent embryonic development is improved
      specifically by FSH.

PMID- 9572436
TI  - Effect of profound suppression of luteinizing hormone during treatment with
      gonadotrophin-releasing hormone analogue and purified follicle stimulating
      hormone upon development of cryopreserved embryos.
AB  - In response to previously published evidence from monkeys, this study examined
      the influence of the degree of luteinizing hormone (LH) suppression during the
      follicular phase of the stimulation cycle, upon cryopreserved embryo survival and
      development. The LH concentration of the mid-follicular phase was assessed in 250
      in-vitro fertilization (IVF) cycles treated with gonadotrophin-releasing hormone
      analogue (GnRHa) and either purified follicle stimulating hormone (FSH) or human
      menopausal gonadotrophin (HMG), and was related to the performance of
      cryopreserved embryos in 351 subsequent embryo transfer cycles. Rates of embryo
      survival, embryo development rates, implantation rates, and pregnancy rates were
      examined with respect to the LH concentration recorded in the mid-follicular
      phase. In contrast to experimental evidence from other primates, there was no
      significant influence of the follicular phase LH concentration upon any of the
      parameters examined.

PMID- 9572437
TI  - Nurses performing embryo transfer: the development and results of the Birmingham
      experience.
AB  - Although in-vitro fertilization treatment is doctor-led, many of its steps are
      performed by nurses. The embryo transfer step, however, is performed exclusively
      by doctors in the majority of units. In our unit, doctors performed embryo
      transfers from June 1994 until December 1995 (period I). From January 1996 until
      May 1997 (period II) the nurses, after appropriate training, performed the
      procedure. When they experienced difficulties during the mock transfer performed
      immediately before the real transfer, or if they were not available to do the
      procedure, a doctor performed it. In period I, 488 embryo transfers were
      performed (all by doctors), with a pregnancy rate per transfer of 35% and an
      implantation rate of 16%. In period II, 522 embryo transfers were performed.
      Nurses performed 371 (71%) and doctors 151 (29%) of the procedures. The pregnancy
      rate per nurse-transfer was 40.2% and per doctor-transfer 41%. The corresponding
      implantation rates were 16.9% and 17%. None of these differences were
      statistically significant (P > 0.05). These data indicate that, with appropriate
      training and medical back-up, nurses can perform the majority of embryo transfers
      with ease and outcome comparable to that of doctor embryo transfer.

PMID- 9572438
TI  - Gamete-specific DNA fragmentation in unfertilized human oocytes after
      intracytoplasmic sperm injection.
AB  - The objective of the present study was to assess the integrity of maternal and/or
      paternal chromatin in injected oocytes that remained unfertilized after
      intracytoplasmic sperm injection (ICSI). The study was performed on 102 oocytes
      that failed to show pronuclear formation 18-20 h after ICSI. We used chromatin
      labelling with 4,6-diamidino-2-phenylindole (DAPI) to identify maternal and
      paternal chromatin, coupled with biotin-mediated end-labelling to assess DNA
      fragmentation in each gamete. It was shown that 50% of oocytes without pronuclear
      formation following ICSI contained chromatin with damaged DNA, and that the
      source of the DNA fragmentation was equally divided between the spermatozoon
      (25.8%) and the oocyte (24.4%). A significantly greater proportion of condensed
      spermatozoa in human oocytes had damaged DNA, compared to decondensed spermatozoa
      (24.7 compared to 5.9%, P=0.002). There was a significant increase in the
      incidence of DNA fragmentation in oocytes from patients older than 35 years (65+/
      1.2%) compared to those from younger patients (36+/-1.0%) (P < 0.05). Further,
      17% of unfertilized oocytes contained no paternal chromatin. Thus, DNA
      fragmentation in both spermatozoa and oocytes is associated with failure of
      fertilization in ICSI. In some cases of severe male factor infertility, a
      significant proportion of spermatozoa injected into oocytes may contain
      fragmented DNA. Injection of oocytes with spermatozoa containing abnormal
      chromatin will probably result in failure of sperm decondensation and
      fertilization. In older women, a significant proportion of oocytes injected may
      contain fragmented DNA. These observations may explain the consistent inability
      of most clinics to achieve fertilization rates higher than 65% with ICSI.

PMID- 9572439
TI  - Ooplasmic injection of elongating spermatids for the treatment of non-obstructive
      azoospermia.
AB  - We applied the technique of ooplasmic elongating spermatid injection to the
      treatment of non-obstructive azoospermia. Mature oocytes were injected with
      elongating spermatids isolated from testicular biopsy material obtained from 13
      non-obstructed azoospermic men. Seventy-three oocytes were successfully injected
      with elongating spermatids and were then cultured for 36 h. At 13 h post
      injection 68 oocytes were found to be activated and 52 of them were fertilized.
      Forty-one 2- to 4-cell stage embryos developed from normally fertilized oocytes
      were transferred. At least two embryos were transferred to each female partner.
      Two pregnancies were achieved. Elongating spermatid injection may have a role in
      the treatment of non-obstructive azoospermia.

PMID- 9572440
TI  - Morphometric evaluation of stromal vascularization in the endometrium in
      adenomyosis.
AB  - A computerized morphometric investigation of stromal vascularization in the
      endometrium during adenomyosis was performed retrospectively. Using a polyclonal
      antibody and a peroxidase-antiperoxidase method, formalin-fixed paraffin sections
      of the tissue were stained for von Willebrand factor, a marker for endothelium.
      The subjects were divided into two groups: 42 patients with histologically proven
      adenomyosis and 29 fertile control subjects, 12 in the proliferative phase and 17
      in the secretory phase. Objective quantitative colour image analysis was used to
      assess the staining intensity and hence the degree of vascularization. In the
      control group, stromal vascularization increased in the secretory phase. In
      adenomyosis, vascularization increased markedly, up to 11.6 times that of the
      controls, in terms of the in total surface area of capillaries per mm2 in the
      endometrium in the proliferative phase. These findings suggest clinical relevance
      to severe functional disturbances such as hypermenorrhoea or iron deficiency
      anaemia.

PMID- 9572441
TI  - The window for embryo transfer in oocyte donation cycles depends on the duration
      of progesterone therapy.
AB  - In 192 oocyte donation cycles performed between January 1993 and July 1996, we
      examined the width of 'the window for embryo transfer' using standard hormonal
      replacement methods. All transfers were performed within 48 h of insemination. We
      varied the day of embryo transfer with regard to the initiation of progesterone
      therapy and, thus, the duration of endometrial exposure to progesterone and
      analysed the resulting pregnancy rates. Patients were divided into five groups (I
      V) and embryo transfers were performed 2, 3, 4, 5 or 6 days following initiation
      of progesterone therapy. The number of pregnancies per transfer cycle achieved in
      groups I-V were 0 (0%), 3 (12%), 16 (40%), 29 (48.3%), and 10 (20.4%)
      respectively. The increased pregnancy rate in group III in comparison to group II
      is statistically significant (P < 0.03). Furthermore, the pregnancy rate in group
      IV (5 days of progesterone administration before embryo transfer) was
      significantly higher than in group V (6 days of progesterone administration
      before embryo transfer; P < 0.005). We also noted that, when embryos were
      transferred 4 or 5 days after initiation of progesterone therapy, the pregnancy
      rates were not significantly different between menopausal and cycling recipients
      (50% vs 43.7%). Our results indicate that the window for embryo transfer is
      dependent on duration of treatment with progesterone; it begins approximately 48
      h after starting progesterone administration and lasts for approximately 4 days.
      The optimum period for transferring embryos at the 4- to 8-cell stage corresponds
      to cycle days 18 and 19. Transfers performed on the 17th and 20th days of the
      cycle can result in successful implantation, although the rates of implantation
      are highest when transfers are done on days 18 and 19.

PMID- 9572442
TI  - Gonadotrophin stimulation of donor females decreases post-implantation viability
      of cultured one-cell hamster embryos.
AB  - Hamster one-cell embryos were collected from two groups of donors: females that
      were super-stimulated with pregnant mare's serum gonadotrophin (PMSG) and females
      that were not. Embryos were cultured for 72 h and scored for development. Morulae
      and blastocysts from the PMSG- and non-stimulated females were transferred into
      contralateral uterine horns of non-stimulated recipient females, so that
      experimental embryos (from PMSG-stimulated females) and control embryos (from non
      stimulated females) were paired within a single recipient. Right and left uterine
      horns of recipient females were examined 11 days later for the number of
      implantation sites and fetuses. After 72 h of culture, development to morulae and
      blastocysts was not significantly different for embryos from PMSG- and non
      stimulated females. However, embryos from PMSG-stimulated females compared to
      controls had significantly reduced mean cell numbers (18 versus 21; P=0.003) and
      a two-fold decrease in viability post-transfer (20 versus 45%; P=0.02). These
      findings indicate that gonadotrophin stimulation compromises subsequent
      developmental competence either during oocyte maturation or in the very early
      embryo, but it is unclear whether reduced viability is a direct effect or is an
      indirect consequence of PMSG stimulation.

PMID- 9572443
TI  - Galectin-1 and -3 in cells of the first trimester placental bed.
AB  - The beta-galactoside-binding proteins galectin-1 and -3 are thought to modulate
      cell-extracellular matrix interactions in cell adhesion and migration. In this
      study, their occurrence in human trophoblast has been investigated. In the first
      trimester placenta galectin-1 is expressed in the cytotrophoblast of the mid and
      distal cell columns, but absent from the villous and proximal column
      cytotrophoblast. The villous syncytiotrophoblast was also positive. Galectin-3,
      on the other hand, was uniformly localized in the villous cytotrophoblast and mid
      and distal cell columns. Immunolocalization of these proteins in placental bed
      tissue has shown that galectin-1 and -3 are not present in cytokeratin-positive
      interstitially migrating cytotrophoblast. The co-localization of galectin-1 with
      extracellular laminin in cultures of cytotrophoblast, choriocarcinoma or decidual
      stromal cells is consistent with a role in the organization of extracellular
      matrix and the regulation of cell motility.

PMID- 9572444
TI  - Ultrasound-guided aspiration of hydrosalpinges is associated with improved
      pregnancy and implantation rates after in-vitro fertilization cycles.
AB  - Previous reports have shown that the presence of hydrosalpinges may have a
      detrimental effect on in-vitro fertilization (IVF) outcomes and salpingectomy has
      been recommended by some authors as a means of improving IVF pregnancy rates. Our
      first objective was to determine the effect of hydrosalpinges diagnosed by
      ultrasound on IVF outcomes in our clinic. Our second objective was to examine the
      effects of aspiration of hydrosalpinges at the time of oocyte retrieval on IVF
      outcomes. Women with hydrosalpinges (n=34) were compared with women who had tubal
      disease but no hydrosalpinges (n=124) and were found to have a reduced clinical
      pregnancy rate (18 % versus 37%, P=0.053), a reduced ongoing pregnancy rate (15
      versus 34%, P=0.051), and a reduced implantation rate (7 versus 18%, P=0.003)
      after IVF procedures. Among women with hydrosalpinges present, 16 had their
      hydrosalpinges aspirated at the time of oocyte retrieval and 18 did not.
      Aspiration of hydrosalpinges was associated with a higher clinical pregnancy rate
      (31 versus 5%, P=0.07), a higher ongoing pregnancy rate (31 versus 0%, P=0.015),
      and a higher implantation rate (14 versus 1%, P=0.015). This study confirms the
      association between the presence of hydrosalpinges and poor IVF outcomes. We find
      that aspiration of hydrosalpinges at the time of oocyte retrieval leads to
      improved pregnancy rates and may be an acceptable alternative to salpingectomy
      for treatment of these patients.

PMID- 9572445
TI  - Three-dimensional intrauterine sonography in the early first-trimester of human
      pregnancy: preliminary study.
AB  - Our purpose was to visualize normal embryonal surface anatomic structures using
      three-dimensional (3D) intrauterine sonography with a 20 MHz flexible catheter
      based high-resolution real-time miniature transducer in the early first trimester
      of pregnancy. A total of 15 women about to undergo therapeutic abortion at 7-9.9
      weeks gestational age were studied by means of 3D intrauterine sonography with a
      specially developed catheter-based high-resolution real-time miniature (2.4 mm in
      outer diameter) ultrasound transducer (20 MHz). This imaging system can provide
      conventional 2D intrauterine sonographic images and can also generate within
      seconds high-quality 3D images in the surface and transparent mode. At week 8,
      prominent forehead was evident, and upper and lower limbs and midgut herniation
      were clearly depicted. At week 9, fingers and toes were depicted as small digital
      rays, and the sacral tail protruded caudally. The midline cranial ectodermal
      cleft was also identified. At week 10, embryonic face and fingers were clearly
      shown. 3D intrauterine sonography provides a novel means for visualizing of
      surface anatomic structures of the human embryo in utero. These results suggest
      that 3D intrauterine sonography can become an important modality in future
      embryological research and in detection of embryonic developmental disorders in
      the early first-trimester pregnancy.

PMID- 9572446
TI  - Second trimester maternal dimeric inhibin-A in the multiple-marker screening test
      for Down's syndrome.
AB  - The aim of this study was to evaluate the additional value of dimeric inhibin-A
      serum concentration in second trimester multiple-marker screening tests for
      pregnancies affected by Down's syndrome. We anticipated that second trimester
      maternal serum dimeric inhibin-A concentrations would be altered in pregnancies
      complicated by fetal Down's syndrome and that dimeric inhibin-A would perform
      better than one of the three substances analysed in the multiple-marker screening
      test currently in use. A total of 1156 serum samples were screened for dimeric
      inhibin-A in parallel with the routine classic triple test screening programme
      performed on a random obstetric population. Classic triple test performance was
      compared with detection rates obtained after substitution of unconjugated
      oestriol by inhibin-A and with the performance of inhibin-A and alpha-fetoprotein
      alone. Absolute dimeric inhibin-A maternal serum concentrations of Down's
      syndrome pregnancies were indeed significantly higher than those of normal
      pregnancies in our screened population. The performance of dimeric inhibin-A in
      combination with the multiple-marker screening test, however, is limited because
      of its strong correlation with intact human chorionic gonadotrophin.

PMID- 9572447
TI  - Pregnancy after heart transplant: update and case report.
AB  - A literature review of 22 cases of pregnancy following cardiac transplantation up
      to 1995 and a case report are presented here. A 30 year old woman, gravida 3,
      para 1, contacted us for obstetric care at 8 weeks gestation, about 55 months
      after orthotopic cardiac transplantation. The transplant had been performed for a
      familial dilative cardiomyopathy, which had become manifest during her previous
      pregnancy. The course of the current gestation was uneventful. The patient's
      cardiovascular function was good throughout the pregnancy. Immunosuppressive
      therapy, the dose of which was increased during pregnancy, included cyclosporine
      and azathioprine. Because of an increase in the patient's plasma uric acid
      concentration and an initial rise in her blood pressure, despite therapy, a
      repeat Caesarean section was performed at 37 weeks gestation. A female baby
      weighing 2330 g, Apgar scores 7/9, was delivered. Mother and infant were
      discharged on postoperative day 15 and are doing well 14 months postpartum.
      Through a review of literature and our case, the issues and problems related to
      pregnancy after a heart transplant are discussed, in particular the maternal
      fetal risks, management, therapy, delivery, neonatal problems and follow-up
      postpartum of mother and baby.

PMID- 9572448
TI  - Induced abortion is not a cause of subsequent preterm delivery in teenage
      pregnancies.
AB  - To examine the possible impact of previous induced abortion on the occurrence of
      preterm delivery in the subsequent pregnancy in teenage women, a retrospective
      case-control study was performed on mothers aged 13-19 years who delivered in one
      tertiary hospital over a 4 year period. Those who had a history of induced
      abortion prior to the index pregnancy were identified from the records and
      compared with a control group without previous induced abortion and who were
      matched for maternal age and parity. Of the 118 cases thus identified, 28 (23.7%)
      had more than one induced abortions and 18 (15.3%) had one or more induced
      abortions in the second trimester. There were 10 (8.5%) para 1 cases. No
      significant differences could be demonstrated between the study and control
      groups in the maternal demographics, major pregnancy complications, or perinatal
      outcome, except for the incidence of smokers which was significantly higher (39.0
      versus 14.4%, P < 0.02) in the study group. The number of previous induced
      abortions did not appear to be related to the incidence of preterm labour, which
      was 10.2 and 8.5% in the study and control groups respectively. Our findings
      indicate that previous induced abortion is not a significant cause of preterm
      labour and delivery in teenage pregnancies.

PMID- 9572450
TI  - A survey of the effectiveness of the assessment of the welfare of the child in UK
      in-vitro fertilization units.
AB  - Seventy-one clinics in the UK offering in-vitro fertilization (IVF) treatment
      were surveyed for their protocols on the assessment of the welfare of the
      children produced. A total of 44 (62%) responded. Of these, five (12%) did not
      have operational protocols, seven (16%) declined to provide their protocols, and
      32 (73%) provided information used in the survey. The information was in the form
      of a protocol for only 16 (50%) of these clinics. The remaining clinics submitted
      as their 'protocols' letters to general practitioners, patient information,
      patient questionnaires and/or a copy of their policy on the assessment of child
      welfare. From the submitted material, it was possible to determine that 94% of
      clinics seek information on aspects of child welfare assessment, 78% have a
      procedure for making further enquiries where there is any cause for concern, 44 %
      include counselling opportunities explicitly in protocols, 30-38% of clinics see
      a full medical and social history from each prospective parent as part of the
      child welfare assessment, 16% include explicit consideration of the impact of
      multiple births on the welfare of the child, and 3% include consideration of the
      issue of disclosure of the mode of conception of the child on its welfare. Most
      clinics did not have clearly defined procedures on how to reach a decision on
      whether or not to treat. Eight clinics (25%) made explicit in their protocols any
      exclusion criteria. It is concluded that clinics are not currently producing
      completely effective protocols. Two possible reasons for this are considered:
      lack of technical knowledge about what constitutes an effective protocol, and
      lack of clear policy development and propagation underlying protocols within
      clinics. Possible approaches to improving the situation are considered.

PMID- 9572449
TI  - Bilateral simultaneous tubal sextuplets: pregnancy after in-vitro fertilization-
      embryo transfer following salpingectomy.
AB  - The presence of a damaged tube has been suggested in recent studies to have a
      negative effect on in-vitro fertilization (IVF) outcome. Performing bilateral
      salpingectomy prior to IVF to maximize pregnancy rates may also result in
      unnecessary surgery. This case is also an example of the occurrence of
      interstitial pregnancy after salpingectomy. This unusual type of ectopic
      pregnancy must be kept in mind when evaluating a patient suspected of a possible
      early abnormal gestation after assisted reproductive technolologies.

PMID- 9572451
TI  - Should sperm donors be paid? A survey of the attitudes of the general public.
AB  - Gamete donation in assisted reproduction is an accepted treatment option for
      certain infertile couples. Traditionally, men donating spermatozoa have been paid
      a nominal fee, whilst women donating oocytes have not. The issue of payment for
      sperm donors has recently attracted attention following the Human Fertilisation
      and Embryology Authority's (HFEA) suggestion that such payment may be withdrawn.
      Prior to the final meeting of the HFEA working party which is examining this
      issue, here we report the results of a survey designed to solicit opinion on
      whether sperm donors should be paid, to identify social or other factors which
      influence this opinion, and to examine the influence of financial incentive on
      potential donors. We surveyed 717 individuals in three distinct groups: the
      general public, students (potential donors), and infertility patients (potential
      recipients). The majority of the potential donor group (students) was in favour
      of paying sperm donors, as were infertility patients. In contrast the general
      public was not. The opinion of the general public on this issue was influenced by
      their prior knowledge of whether donors were paid: those of the general public
      favouring the payment of sperm donors had a prior awareness that such payments
      were made. Although not in favour of paying sperm donors, the general public
      overwhelmingly approved of the use of donated spermatozoa for the treatment of
      infertile couples, and thought that ways should be sought to increase the
      availability of donor spermatozoa for the treatment of infertility and for
      research purposes. Within the potential donor group (students), the majority
      indicated that financial reward was an important factor which would influence
      their decision to donate spermatozoa. As the majority of both the potential
      recipients and potential donors feels that sperm donors should be paid, perhaps
      the views of these groups should carry significant weight when the decision
      whether or not to withdraw payment is taken. This is especially the case in view
      of the fact that the majority of the general public is in favour of the use of
      donated spermatozoa for the treatment of infertile couples.

PMID- 9572452
TI  - The in-vitro effects of nicotine and cotinine on sperm motility.

PMID- 9572453
TI  - Theories of the pathophysiology of ovarian hyperstimulation syndrome should be
      based on the newest knowledge.

PMID- 9572454
TI  - Toronto's Hospital for Sick Children study of traumatic sudden sensorineural
      hearing loss.
AB  - OBJECTIVE: Traumatic sudden sensorineural hearing loss (SHL) is by definition a
      hearing loss of greater or equal to 30 dB occurring within 3 days of trauma. The
      objective of this study was to assess the rate of traumatic sudden SHL. Etiology
      is discussed with statistical references, and appropriate treatment is proposed.
      A case study of an enlarged vestibular aqueduct illustrates the above. METHOD:
      The authors retrospectively studied cases at The Hospital for Sick Children,
      Toronto, between the years 1980 and 1995. High-resolution CT scans of the
      temporal bones with bone algorithms and coronal/axial views were performed on all
      children presenting with SHL after 1988. RESULTS: Of the 12 children studied, 9
      had high-resolution CT scans, revealing a 33% incidence each of inner-ear
      malformations, temporal bone fractures, and other miscellaneous CT findings.
      CONCLUSION: By corollary, the authors recommend a high index of suspicion for
      congenital temporal bone abnormalities in all cases of sudden sensorineural
      hearing loss, particularly those associated with trauma.

PMID- 9572455
TI  - Comparative cost analysis of myringotomy with insertion of ventilation tubes in
      Ontario and British Columbia.
AB  - OBJECTIVE: The purpose of this study was to conduct a comparative cost analysis
      of myringotomy with insertion of ventilation tube (MVT) for children performed at
      two regional paediatric centres: The Hospital for Sick Children, and the British
      Columbia Children's Hospital. DESIGN: Comparative cost analysis. SETTING: The
      Hospital for Sick Children (HSC), Toronto, and the British Columbia Children's
      Hospital (BCCH), Vancouver. METHODS: The cost analysis was performed from a
      health system perspective using a treatment protocol developed through a review
      of the literature and input from staff from each of the study hospitals. MVT cost
      estimates were derived, including direct treatment costs and overhead costs.
      RESULTS: Total costs per MVT case (in 1994 Canadian dollars: Cdn$ 1.00
      approximately US$ 0.75) varied from $390.81 at BCCH to $455.63 at HSC. Regional
      variations in physician costs accounted for almost 70% of the difference in MVT
      case costs. The distribution of nonphysician MVT case costs were similar in each
      study hospital, with direct (nonphysician) surgical costs, preoperative
      assessment and recovery room costs, and administration accounting for 30%, 26%,
      and 44% of total nonphysician costs, respectively. CONCLUSIONS: This study
      identified the magnitude and determinants of regional variations in the cost of
      MVT surgery. Such cost estimates serve as an important (but not the sole)
      ingredient in service cost-effectiveness deliberations and in the formulation of
      evidence-based care when health care resources are scarce.

PMID- 9572456
TI  - Esophagolaryngeal reflex in a porcine animal model.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of stimulation
      of the distal esophagus upon tension in the thyroarytenoid muscles. METHOD:
      Stimulation of the distal esophagus of six anaesthetized female pigs by means of
      balloon dilatation and acid infusion was performed. Response was measured with
      electromyography of the thyroarytenoid muscles. RESULTS: Acid infusion into the
      distal esophagus showed a statistically significant response in the thyroaytenoid
      muscles. Response to balloon dilatation was marked but not statistically
      significant. CONCLUSION: Stimulation of the distal esophagus during episodes of
      gastroesophageal reflux may play a causative role in producing some of the
      symptoms that otolaryngologists treat on a daily basis.

PMID- 9572457
TI  - Isolated plexiform neurofibroma of tongue and oropharynx: a rare manifestation of
      von Recklinghausen's disease.

PMID- 9572458
TI  - Rosai-Dorfman disease: presenting as isolated extranodal involvement of larynx.

PMID- 9572460
TI  - Laryngeal sarcoidosis with airway obstruction.

PMID- 9572459
TI  - Tracheal leiomyoma.

PMID- 9572461
TI  - Bilateral pleomorphic adenoma of the parotid gland.

PMID- 9572462
TI  - Postoperative Meleney's ulcer.

PMID- 9572463
TI  - Angiolipoma of the head and neck.

PMID- 9572464
TI  - Primary laryngeal melanoma.

PMID- 9572465
TI  - Use of fibrin glue in maxillofacial surgery.
AB  - OBJECTIVE: To describe various applications of homologous fibrin glue in
      maxillofacial surgery. The clinical outcomes of the treated cases are discussed.
      METHODS: During the period January 1993 to July 1995, 71 patients underwent
      maxillofacial procedures in which homologous fibrin glue was utilized. The
      material used in each case was Tisseel, which is composed of human fibrinogen and
      bovine thrombin. The material was used to provide close and secure re
      approximation of soft tissue in 20 patients requiring coronal flaps. Bone or
      alloplast fixation was undertaken with fibrin sealant in 14 patients. In 13 cleft
      lip and palate patients, the material was used in the repair of residual fistulas
      or clefts. Twelve patients had sinus lift procedures where the material fixated
      the bone graft and repaired the torn mucoperiosteal lining. Finally, 12 patients
      with coagulopathies had fibrin glue placed following exodontia. All patients were
      followed for a minimum of 6 months postoperatively. RESULTS: Seventy patients
      treated with Tisseel had successful outcomes as determined by preoperative
      criteria. A single oral antral fistula recurred 3 weeks after surgery. No adverse
      reaction to the material was noted in any of the patients. CONCLUSIONS:
      Homologous fibrin glue has various applications in the field of maxillofacial
      surgery and can be used with safe and predictable results.

PMID- 9572466
TI  - Do sports nasal strips improve nasal airflow? A preliminary report.

PMID- 9572467
TI  - The history of otolaryngology in Canada: University of Alberta.

PMID- 9572468
TI  - Vascular endothelial growth factor (VEGF) activates Raf-1, mitogen-activated
      protein (MAP) kinases, and S6 kinase (p90rsk) in cultured rat cardiac myocytes.
AB  - Rapid activation of intracellular signaling cascades is induced in cardiac
      myocytes in response to various external stresses. Vascular endothelial growth
      factor (VEGF) is a potent angiogenic mitogen secreted from tumor cells and cells
      exposed to hypoxia such as ischemic myocardial cells. To clarify the mechanisms
      of how cardiac myocytes respond and adapt to ischemic stresses, we investigated
      the intracellular signaling cascades in cultured rat cardiac myocytes in response
      to VEGF. We show that rapid activation of mitogen-activated protein kinase kinase
      kinase (MAPKKK) of Raf-1, MAP kinases, and S6 kinase (p90rsk) was induced in
      cardiac myocytes in response to VEGF. This activation of MAP kinases was also
      induced in fibroblasts. VEGF also caused phosphorylation of the activating
      transcription factor 2. Furthermore, VEGF strongly induced a transcription factor
      jun-B mRNA in cardiac myocytes. These results indicated that MAP kinase pathway
      is rapidly activated in cardiac myocytes and fibroblasts in response to VEGF. It
      is strongly suggested that cardiac myocytes are one of the targets of VEGF and
      that cardiac response to ischemic stresses may be at least partly mediated by
      VEGF.

PMID- 9572469
TI  - Suppression of interleukin-11-mediated bone resorption by cyclooxygenases
      inhibitors.
AB  - We previously found that human melanoma (A375M) and human breast cancer (MDA-MB
      231) cells formed osteolytic bone metastasis in vivo. These cancer cells produced
      interleukin-11 (IL-11) by themselves and stimulated its production from
      osteoblasts. Interleukin-11 could increase the number of osteoclasts and raise
      the calcium concentration in the medium of neonatal murine calvaria organ
      culture, indicating bone resorption in vitro. Therefore, IL-11 could play an
      important role in the promotion of osteolysis at the site of bone metastasis. In
      the present study, we used the calvaria culture system to try to clarify the
      mechanisms of IL-11-mediated bone resorption. The murine calvaria expressed both
      the specificity-determining alpha subunit and the signal-transducing beta subunit
      (gp130) of the IL-11 receptor. When IL-11 was added to the calvaria culture, the
      concentrations of prostaglandin E2 (PGE2) was elevated. Pretreatment of calvaria
      with cyclooxygenases inhibitors (e.g., indomethacin, NS-398, and dexamethasone)
      suppressed the production of PGE2 and the bone resorption induced by IL-11.
      Addition of exogenous PGE2 overcame the inhibitory effect of cyclooxygenases
      inhibitors and promoted bone resorption. These results indicate that IL-11
      promotes bone resorption through a PGE2 synthesis-dependent mechanism and that
      cyclooxygenases inhibitors could be interesting drugs to suppress IL-11-mediated
      osteolytic bone metastasis of cancer cells.

PMID- 9572470
TI  - Regulation of platelet heparanase during inflammation: role of pH and
      proteinases.
AB  - Heparan sulfate is rapidly degraded by an endoglycosidase (heparanase) secreted
      by activated platelets. Since the cleavage and release of heparan sulfate would
      profoundly alter the local physiology of the endothelium, platelet heparanase
      activity should be tightly regulated. Consistent with this hypothesis, platelet
      heparanase was found to degrade endothelial cell heparan sulfate at pH 6.0 but
      not at pH 7.4, even though 25% of maximum activity was detected at pH 7.4. Loss
      of heparanase activity occurred rapidly (t1/2 is approximately equal to 20 min)
      and reversibly at physiologic pH but did not occur at acidic pH (<7.0).
      Inactivation of heparanase at pH 7.4 did not affect heparin binding and was
      reversed by 0.5 M NaCl or by heparan sulfate but not by chondroitin sulfate,
      suggesting inactive heparanase could be tethered on cell surfaces and the
      function regulated by heparan sulfate. Heparanase was gradually inactivated by
      trypsin and urokinase (t1/2 = 5 h) but resisted cleavage by leukocyte cathepsin
      G, leukocyte elastase, plasmin, and thrombin. These findings are consistent with
      a model in which platelet heparanase is active at the low pH of inflammation but
      inactive under physiologic conditions preventing inadvertent cleavage of heparan
      sulfate and loss of physiologic functions of endothelial cells.

PMID- 9572471
TI  - Interaction of human neutrophils with airway epithelial cells: reduction of
      leukotriene B4 generation by epithelial cell derived prostaglandin E2.
AB  - Airway epithelial cells (AEC) play an active role in the regulation of
      inflammatory airway disease. In the present study we analyzed the interaction of
      AEC with polymorphonuclear leukocytes (PMN) in coincubation with respect to their
      arachidonic acid (AA) metabolism using reversed phase-HPLC and post-HPLC-ELISA.
      Primary cultures of porcine AEC released predominantly PGE2, PGF2a, and 15
      hydroxyeicosatetraenoic acid (15-HETE), whereas the major human PMN-derived AA
      metabolite was the chemotactic factor leukotriene B4 (LTB4). In AEC-PMN
      cocultures stimulated with the calcium ionophore A23187, PMN-related 5
      lipoxygenase products were decreased by 45%. This reduction in LTB4 formation in
      the presence of AEC was mainly due to PGE2 generated by the epithelial cells,
      whereas 15-HETE made a minor contribution. Most of the effect was inhibited by
      AEC pretreatment with acetylsalicylic acid and restored by addition of equivalent
      amounts of exogenous PGE2. LTB4 degradation was not enhanced in PMN-AEC
      coincubations. Moreover, reduction of LTB4 formation in this system did not
      require an intimate cell-to-cell contact as shown by studies involving filter
      membranes for PMN-AEC separation. Superoxide anion concentrations were also
      decreased in PMN-AEC coincubations; this effect, however, was unrelated to PGE2
      for quantitative reasons and was probably due to O2- degradation by epithelial
      cells. In summary, epithelially derived PGE2 is the major mediator in the
      coincubation of porcine AEC and human PMN that downregulates neutrophil responses
      by activating receptors on the neutrophil. A minor contributor in this course of
      PMN-AEC interaction may be the 15-HETE transcellular pathway. Overall, airway
      epithelium appears to play an antiinflammatory role by damping the
      proinflammatory potential of neutrophils.

PMID- 9572472
TI  - Modulation of ICAM-1 expression by alpha-MSH in human melanoma cells and
      melanocytes.
AB  - Alpha-MSH, a proopiomelanocortin (POMC)-derived peptide, is known to be produced
      in the pituitary, the skin, and melanoma tumors and to possess many biological
      effects, mainly on melanocyte pigmentation and growth. Moreover, the melanocyte
      expresses adhesion molecules, including ICAM-1. The latter has been reported to
      play a role in melanoma spread and associated metastatic process. We conducted a
      study in order to evaluate the possible effect of MSH on ICAM-1 expression in
      human cultured malignant and normal melanocytes. Our data show that alpha-MSH
      inhibits ICAM-1 expression stimulated by TNF in a concentration-dependent manner,
      both at the protein and gene expression level. Ninety percent inhibition was
      obtained with 10 nM MSH, while 50% inhibition was achieved with 1 nM. Endogenous
      cAMP elevation with forskolin as well as an exogenous cAMP stable analogue (Sp
      cAMPS) produced the same inhibitory effect. A screening of malignant melanocytes
      showed that inhibition of ICAM-1 expression could be achieved only in those cells
      expressing detectable MSH receptors and seemed to correlate with the number of
      binding sites. In conclusion, our data strongly suggest alpha-MSH as a potent
      inhibitor of ICAM-1 expression in malignant melanocytes acting through MSH
      receptor stimulation and subsequent cAMP increase.

PMID- 9572473
TI  - Calcium pool size modulates the sensitivity of the ryanodine receptor channel and
      calcium-dependent ATPase of heavy sarcoplasmic reticulum to extravesicular free
      calcium concentration.
AB  - We have examined calcium cycling and associated ATP consumption by isolated heavy
      sarcoplasmic reticulum (HSR) vesicles incubated in conditions believed to exist
      in resting muscle. Our goals were to estimate the magnitude of calcium cycling
      under those conditions and identify the main mechanisms involved in its
      regulation. The integrity of the HSR vesicles was documented by the retention of
      [14C]-sucrose and electron microscopy. HSR actively exchanged Ca2+ with the
      medium through a partially open ryanodine-binding channel (RyR), as evidenced by
      the rapid attainment of a steady-state gradient between HSR and medium, which was
      promptly increased by the closure of the channel with ruthenium red (RR) or
      collapsed by its opening with caffeine. The ATP dependency was evidenced by the
      sustained ATP consumption after the steady state was attained and by the
      abrogation of the gradient following inhibition of the pump with thapsigargin
      (Tg) or the omission of ATP. When HSR vesicles were incubated in a comparatively
      large pool of calcium (approximately 1 micromol/mg HSR protein), ATP consumption
      was 1-1.5 micromol x [min x mg protein](-1) at 0.1 microM free Ca2+. Under such
      conditions, the main regulator of the sarcoplasmic Ca2+-dependent ATPase (SERCA)
      was extravesicular-free Ca2+ concentration, with a four- to fivefold increase
      between 0.1 and 2 microM Ca2+, whereas RyR channel activity and the replenishment
      of the HSR vesicles had only a modest effect on ATP consumption. When calcium
      pool size was reduced to 0.1 micromol/mg HSR protein, a steady state was
      established at a lower level of HSR calcium. In spite of a slightly lower free
      extravesicular Ca2+ at equilibrium (approximately 0.07 microM following an
      initial concentration of 0.1 microM), both ATP consumption and the open
      probability of the RyR channel were increased by a factor of three to five.
      Compared to the large calcium pool, the sensitivity of both RyR channel and SERCA
      to extravesicular free Ca2+ concentration as well as to caffeine and RR was
      markedly enhanced. CONCLUSIONS: 1) In conditions present in resting muscle, HSR
      calcium is in dynamic equilibrium with the medium through a partially open RyR
      channel, which requires continuous ATP hydrolysis. 2) The availability of calcium
      is a major determinant of the sensitivity of both RyR channel and SERCA to free
      extravesicular Ca2+ and possibly other stimuli. 3) These observations are
      consistent with the concept that calcium cycling in resting muscle may account
      for a significant fraction of muscle energy demands and further suggest that
      restricting calcium availability may enhance the energetic demands of this
      process.

PMID- 9572474
TI  - Altered expression of inhibitory guanine nucleotide regulatory proteins (Gi
      proteins) in experimental hepatocellular carcinoma.
AB  - Guanine nucleotide regulatory proteins (G-proteins) play an important role in the
      onset and progression of malignancy. We hypothesized that alterations in
      inhibitory G-protein (Gi) expression and/or function may contribute to cellular
      invasion and formation of hepatocellular carcinoma (HCC). H4IIE hepatoma cells
      were inoculated directly into the liver parenchyma of ACI strain rats, and
      membranes were prepared from HCC livers and adjacent nonneoplastic livers 12 days
      following the initial inoculation. Expression of inhibitory Gialpha proteins was
      determined by Western blot analysis and changes in the functional activity of
      these proteins confirmed by pertussis toxin catalyzed ADP ribosylation and
      adenylyl cyclase activity. Inhibitory Gialpha1, Gialpha1/2, and Gialpha3 protein
      expression was significantly elevated in HCC when compared to adjacent
      nonneoplastic liver and sham-operated hepatic tissue. Pertussis toxin catalyzed
      ADP ribosylation of Gialpha substrates was significantly enhanced in HCC
      concomitant with increased basal and stimulated adenylyl cyclase activity
      following uncoupling of Gi-proteins with manganese ions. The role of Gi-proteins
      in cellular proliferation was confirmed using cultured H4IIE cells and normal
      hepatocytes. In quiescent H4IIE cells, mastoparan (Gialpha activator) increased
      [3H] thymidine incorporation and cell growth in a dose-dependent manner, whereas
      both pertussis toxin (a Gi-protein inhibitor) and 8-bromo-cAMP inhibited
      mitogenesis. In contrast, in isolated cultured hepatocytes, mastoparan inhibited
      [3H] thymidine incorporation, while pertussis toxin and 8-bromo-cAMP were
      mitogenic. We conclude that HCC is associated with marked changes in Gialpha
      protein expression in vivo and in vitro, direct activation of which leads to
      increased mitogenesis in H4IIE cells in vitro.

PMID- 9572475
TI  - Lack of transforming growth factor-beta type II receptor expression in human
      retinoblastoma cells.
AB  - Retinoblastoma cells are resistant to transforming growth factor-beta (TGF-beta)
      activity due to the absence of TGF-beta binding. To further elucidate the
      mechanism of TGF-beta resistance, we studied the expression of the TGF-beta
      receptors and SMADs by using the Y79 and WERI-Rb-1 retinoblastoma cell lines.
      Binding of 125I-TGF-beta1 to serine/threonine kinase receptor type II (TbetaR-II)
      and TbetaR-I was not seen in the retinoblastoma cells. TbetaR-II mRNA was not
      expressed in these cells, but TbetaR-I mRNA was detected. Mutation analysis
      revealed no mutation in the coding region of the TbetaR-II gene, and TbetaR-II
      mRNA could be induced after the differentiation of Y79 cells. Smad2, Smad3, and
      Smad4, which are involved in TGF-beta signaling, were expressed in the
      retinoblastoma cells. Transcriptional activation of the TGF-beta-responsive genes
      was not seen by the transfection of either receptor cDNA alone but could be
      induced by transfection of both TbetaR-II and TbetaR-I. These data suggest that
      the defect in the TGF-beta response is caused by the lack of TbetaR-II in the
      retinoblastoma cells. In addition, TbetaR-I may be functionally inactivated in
      these cell lines.

PMID- 9572476
TI  - Overexpression of PKCepsilon in R6 fibroblasts causes increased production of
      active TGFbeta.
AB  - In previous studies, our laboratory demonstrated that Rat 6 (R6) fibroblasts
      which stably overproduce high levels of PKCepsilon display abnormalities in
      growth control that are characteristic of malignant transformation (Cacace et
      al., 1993, Oncogene, 8:2095-2104). The R6-PKCepsilon overproducing cell lines
      also exhibited a decreased growth factor requirement. The present study
      demonstrates that conditioned medium (CM) from two individual clones, R6
      PKCepsilon 10 and 30, stimulates DNA synthesis in control R6-C1 cells. Maximal
      DNA synthesis and morphologic transformation was achieved in control cells when
      they were treated with medium from R6-PKCepsilon cells grown in the presence of
      TPA (TPA-CM). Size fractionation of the TPA-CM from PKCepsilon 30 cells revealed
      that this activity is due to a factor(s) that has an apparent molecular weight in
      the range of 10-30 kD and is heat and acid stable. This factor, like TGFbeta1,
      stimulated anchorage-independent growth of NRK cells. Western blot analysis
      (under nonreducing conditions) of the TPA-CM from R6-PKCepsilon 30 and R6
      PKCepsilon 10 cells revealed the presence of the 25 kD active forms of TGFbeta2
      and 3. These active forms of TGFbeta were not found in the CM of control R6
      cells, or R6 cells that overexpress PKCalpha or PKCbeta1. The addition of a pan
      specific TGFbeta antibody to NRK cells treated with the 10-30 kD fraction of TPA
      CM from PKCepsilon 30 cells blocked the ability of this material to stimulate
      thymidine incorporation. Taken together, these studies suggest that the oncogenic
      activity of PKCepsilon in R6 cells is due, at least in part, to its ability to
      induce production of the active forms of TGFbeta2 and 3.

PMID- 9572477
TI  - Tensional homeostasis in dermal fibroblasts: mechanical responses to mechanical
      loading in three-dimensional substrates.
AB  - Many soft connective tissues are under endogenous tension, and their resident
      cells generate considerable contractile forces on the extracellular matrix. The
      present work was aimed to determine quantitatively how fibroblasts, grown within
      three-dimensional collagen lattices, respond mechanically to precisely defined
      tensional loads. Forces generated in response to changes in applied load were
      measured using a tensional culture force monitor. In a number of variant systems,
      resident cells consistently reacted to modify the endogenous matrix tension in
      the opposite direction to externally applied loads. That is, increased external
      loading was followed immediately by a reduction in cell-mediated contraction
      whilst decreased external loading elicited increased contraction. Responses were
      cell-mediated and not a result of material properties of the matrices. This is
      the first detailed characterisation of a tensional homeostatic response in cells.
      The maintained force, after 8 h in culture, was typically around 40-60
      dynes/million cells). Maintenance of an active tensional homeostasis has
      widespread implications for cells in culture and for whole tissue function.

PMID- 9572478
TI  - Transcription of the beta2-adrenergic receptor gene in rat liver is regulated
      during early postnatal development by an upstream repressor element.
AB  - As early postnatal development of the male rat proceeds, there is a decline in
      transcription of the beta2-adrenergic receptor gene in liver which is associated
      with a decline in beta2-adrenergic receptor mediated glucose mobilization. In
      this study, primary cultures of rat hepatocytes transiently transfected with
      fusion genes containing various segments of beta2-adrenergic receptor gene 5'
      flanking DNA fused to a promoterless luciferase reporter gene were used to
      identify genetic elements that might control beta2-adrenergic receptor gene
      expression during the first 10 days of postnatal life. We found that 261 bp of
      beta2-adrenergic receptor gene 5'-flanking region (-372 to -95, start of
      translation is +1) was sufficient to direct high luciferase expression in fetal
      day 18 hepatocytes and therefore included the beta2-adrenergic receptor gene
      promoter. Luciferase activities in fetal day 18 hepatocytes transfected with
      pbeta2AR(-372/-95), pbeta2AR(-1,335/-95) and pbeta2AR(-3,349/-95) were fourfold
      greater than that in either postnatal day 5 or postnatal day 10 hepatocytes
      transfected with the same fusion genes. By use of gel mobility shift assays, we
      observed increased protein binding to a 50 bp segment (-372 to -323) of the beta2
      adrenergic receptor gene 5'-flanking region with nuclear extracts prepared from
      postnatal day 5 and postnatal day 10 hepatocytes compared to fetal day 18
      hepatocytes. These findings suggest the presence of a regulatory element in the
      5'-flanking region of the beta2-adrenergic receptor gene that appears to be
      involved in suppression of transcription of the beta2-adrenergic receptor gene in
      liver during early postnatal development.

PMID- 9572479
TI  - Signaling pathways mediating induction of the early response genes prostaglandin
      G/H synthase-2 and egr-1 by serotonin via 5-HT2A receptors.
AB  - Signaling pathways responsible for serotonin (5-HT)-mediated induction of early
      response genes prostaglandin G/H synthase-2 (PGHS-2, cyclooxygenase-2) and egr-1
      were investigated in rat mesangial cells. Gene induction by 5-HT was dependent on
      5-HT2A receptors that were pertussis toxin insensitive indicating coupling to a G
      protein of the Gq family. Binding of 5-HT to this receptor activates
      phosphatidylinositol-specific phospholipase C (PLC) and release of Ca2+ from
      internal stores, but this activation was not related to PGHS-2 mRNA expression.
      Similarly, PI-3 kinase was not involved in 5-HT signaling. Instead, inhibition of
      phosphatidylcholine-specific PLC interfered with PGHS-2 and egr-1 mRNA induction,
      suggesting this enzyme as a link between 5-HT2A receptors and protein kinase C,
      an essential part of 5-HT-mediated signaling. The MAP kinase pathway was
      identified as common signaling pathway of 5-HT or phorbol ester-induced gene
      expression. Increase of intracellular cAMP by forskolin or dibutyryl cAMP did not
      induce PGHS-2 or egr-1 mRNA expression by itself, but strongly inhibited 5-HT
      mediated mRNA induction. PGHS-2 mRNA and protein induction by 5-HT was also
      abolished by chelation of Ca2+ ions by EGTA, suggesting involvement of Ca2+
      dependent enzymes. In contrast, egr-1 mRNA expression was superinduced in the
      presence of EGTA. Induction of Egr-1 protein was not changed by EGTA hinting to
      Ca2+-sensitive posttranscriptional steps. Activation of the Gq-coupled 5-HT2A
      receptor thus leads to the expression of the early response genes PGHS-2 and egr
      1, using common as well as differing signaling elements that allow differential
      regulation of the expression of these genes that are functionally related to
      renal hemodynamics and proliferation of mesangial cells, respectively.

PMID- 9572480
TI  - Activation of p42/p44 mitogen-activated protein kinase by angiotensin II,
      vasopressin, norepinephrine, and prostaglandin F2alpha in hepatocytes is
      sustained, and like the effect of epidermal growth factor, mediated through
      pertussis toxin-sensitive mechanisms.
AB  - Several agents that act through G-protein-coupled receptors and also stimulate
      phosphoinositide-specific phospholipase C (PI-PLC), including angiotensin II,
      vasopressin, norepinephrine, and prostaglandin (PG) F2alpha, activated the ERK1
      (p44mapk) and ERK2 (p42mapk) members of the mitogen-activated protein (MAP)
      kinase family in primary cultures of rat hepatocytes, measured as phosphorylation
      of myelin basic protein (MBP) by a partially purified enzyme, immunoblotting, and
      in-gel assays. All these agonists induced a peak activation (two to threefold
      increase in MBP-phosphorylation) at 3-5 min, followed by a brief decrease, and
      then a sustained elevation or a second increase of the MAP kinase activity that
      lasted for several hours. Although all the above agents also stimulated PI-PLC,
      implicating a Gq-dependent pathway, the elevations of the concentration of
      inositol (1,4,5)-trisphosphate did not correlate well with the MAP kinase
      activity. Furthermore, pretreatment of the cells with pertussis toxin markedly
      reduced the MAP kinase activation by angiotensin II, vasopressin, norepinephrine,
      or PGF2alpha. In addition, hepatocytes pretreated with pertussis toxin showed a
      diminished MAP kinase response to epidermal growth factor (EGF). The results
      indicate that agonists acting via G-protein-coupled receptors have the ability to
      induce sustained activation of MAP kinase in hepatocytes, and suggest that Gi
      dependent mechanisms are required for full activation of the MAP kinase signal
      transduction pathway by G-protein-coupled receptors as well as the EGF receptor.

PMID- 9572481
TI  - Inhibition of cell growth in NIH/3T3 fibroblasts by overexpression of manganese
      superoxide dismutase: mechanistic studies.
AB  - NIH/3T3 mouse fibroblasts were transfected with the cDNA for manganese superoxide
      dismutase (MnSOD), and two clones overexpressing MnSOD activity were subsequently
      characterized by comparison with parental and control plasmid-transfected cells.
      One clone with a 1.8-fold increase in MnSOD activity had a 1.5-fold increase in
      glutathione peroxidase (GPX) activity (increased GPX-adapted clone), while a
      second clone with a 3-fold increase in MnSOD activity had a 2-fold decrease in
      copper, zinc superoxide dismutase (CuZnSOD) activity (decreased CuZnSOD-adapted
      clone). Increased reactive oxygen species (ROS) levels compared with parental or
      control plasmid-transfected cells were observed in nonsynchronous cells in the
      increased GPX-adapted clone, but not in the decreased CuZnSOD-adapted clone. The
      two MnSOD-overexpressing clones showed different sensitivities to agents that
      generate oxidative stress. Flow cytometry analysis of the cell cycle showed
      altered cell cycle progression in both MnSOD-overexpressing clones. During
      logarithmic growth, both MnSOD-overexpressing clones showed increased
      mitochondrial membrane potential compared with parental and control plasmid
      transfected cells. Both MnSOD-overexpressing clones showed a decrease in
      mitochondrial mass at the postconfluent phase of growth, suggesting that
      mitochondrial mass may be regulated by MnSOD and/or ROS levels. Our results
      indicate that adaptation of fibroblasts to overexpression of MnSOD can involve
      more than one mechanism, with the resultant cell phenotype dependent on the
      adaptation mechanism utilized by the cell.

PMID- 9572482
TI  - Extracellular matrix induced by TGFbeta impairs insulin signal transduction in
      3T3-L1 preadipose cells.
AB  - When 3T3-L1 preadipose cells are exposed to transforming growth factor beta
      (TGFbeta), they synthesize more extracellular matrix (ECM) and resist
      differentiation-inducing stimuli. The mechanism by which ECM suppresses adipose
      cell differentiation (adipogenesis) remains unknown. Since adipogenesis is an
      insulin/insulin-like growth factor-1 (IGF-1)-dependent process, we investigated
      whether TGFbeta-induced ECM inhibits insulin signaling. When preadipose cells
      were pretreated overnight with TGFbeta, we observed a 75% decrease in insulin
      stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)
      compared to that in control cells. Culturing 3T3-L1 preadipose cells on
      fibronectin, a component of the ECM induced by TGFbeta, also inhibited insulin
      dependent IRS-1 tyrosine phosphorylation and adipogenesis, supporting a role for
      ECM in mediating TGFbeta's inhibitory effect on insulin signaling. Since the
      insulin-stimulated association of phosphoinositide (PI) 3-kinase with IRS-1
      depends on IRS-1 tyrosine phosphorylation, we measured the presence of the PI 3
      kinase 85 kDa regulatory subunit in anti-IRS-1 immunoprecipitates. Following
      insulin stimulation, PI 3-kinase-IRS-1 association was reduced by 70% in TGFbeta
      pretreated vs. control preadipose cells. However, insulin-stimulated cellular
      production of PI(3,4,5)P3 was unaltered by TGFbeta pretreatment. This suggests
      that IRS-1-associated p85-type PI 3-kinase may represent a particular subset of
      total cellular PI 3-kinase that is specifically inhibited by TGFbeta. Reduction
      of insulin-stimulated association of IRS-1 with p85-type PI 3-kinase by TGFbeta
      may be one potential mechanism through which TGFbeta blocks 3T3-L1 adipose cell
      differentiation.

PMID- 9572483
TI  - Protein kinase C beta modulates thrombin-induced Ca2+ signaling and endothelial
      permeability increase.
AB  - We investigated the function of the Ca2+-dependent protein kinase C (PKC) beta1
      in the regulation of endothelial barrier property. Human dermal microvascular
      endothelial cells (HMEC-1) were transduced with full-length PKCbeta1 antisense
      (AS) cDNA or control pLNCX vector to generate stable cell lines (HMEC-AS and HMEC
      pLNCX, respectively). Analyses indicated that HMEC-AS expressed the antisense
      PKCbeta1 transcript with decreased PKCbeta protein level (without a change in
      PKCalpha or PKCepsilon). The baseline transendothelial 125I-albumin clearance
      rates of HMEC-1, HMEC-pLNCX, and HMEC-AS were 5.0+/-0.5 x 10(-2), 6.8+/-0.4 x 10(
      2), and 6.9+/-0.6 x 10(-2) microl/min, respectively. Activation of HMEC-1 and
      HMEC-pLNCX with phorbol 12-myristate 13-acetate (PMA) increased the rates to the
      respective 14.5+/-1.7 x 10(-2) microl/min and 16.9+/-2.8 x 10(-2) microl/min
      (corresponding to 191% and 149% increases over baseline). However, in HMEC-AS,
      PMA increased the rate to 9.8+/-1.0 x 10(-2) microl/min (42%). When HMEC-1 and
      HMEC-pLNCX were activated with thrombin, the rates increased to 10.8+/-1.4 x 10(
      2) and 14.0+/-1.9 x 10(-2) microl/min, respectively (116% and 106%). In contrast,
      thrombin stimulation of HMEC-AS more than doubled the increase to 27.2+/-3.5 x
      10(-2) microl/min (294%). Furthermore, the thrombin-induced peak increase in the
      [Ca2+]i in HMEC-AS was greater than in control cells. Fluorescence-activated cell
      sorter analysis of thrombin receptor expression indicated that the augmented
      thrombin-induced responses were not attributable to altered receptor density in
      HMEC-AS. These results indicate that PKCbeta functions in a negative feedback
      manner to inactivate thrombin-generated signals and thereby modulates the
      endothelial permeability increase. Because decreased PKCbeta expression
      significantly reduced the PMA-induced permeability increase, PKCbeta may
      downregulate thrombin receptor function upstream of PKC activation (i.e., Ca2+).

PMID- 9572484
TI  - Activation of the wt1 Wilms' tumor suppressor gene by NF-kappaB.
AB  - The Wilm's tumor suppressor gene, wt1, is expressed in a very defined spatial
      temporal fashion and plays a key role in development of the urogenital system.
      Transacting factors governing wt1 expression are poorly defined. The presence of
      putative kappa-B binding sites within the wt1 gene prompted us to investigate
      whether members of the NF-kappaB/Rel family of transcription factors are involved
      in regulating wt1 expression. In transient transfection assays, ectopic
      expression of p50 and p65 subunits of NF-kappaB stimulated wt1 promoter activity
      10-30-fold. Deletion mutagenesis revealed that NF-kappa-B responsiveness is
      mediated by a short DNA fragment located within promoter proximal sequences of
      the major transcription start site. Two kappaB-binding sites are present in this
      region and form specific complexes with purified NF-kappaB proteins, as revealed
      by electrophoretic mobility gel shift assays. Ectopic expression of p50 and p65
      resulted in increased transcription of the endogenous wt1 gene, as revealed by
      nuclear run-on experiments. Taken together, these results indicate that members
      of the NF-kappaB/Rel family are important for activating expression of wt1 and
      reside upstream of the regulatory cascade leading to wt1 activation.

PMID- 9572485
TI  - E1B 55K sequesters WT1 along with p53 within a cytoplasmic body in adenovirus
      transformed kidney cells.
AB  - WT1 encodes a tumor suppressor that is expressed in cells of the developing
      kidney and is inactivated in Wilms tumor, a pediatric kidney cancer. The
      adenovirus E1B 55K gene product contributes to the transformation of primary baby
      rat kidney (BRK) cells by binding and inactivating the product of the p53 tumor
      suppressor. We have previously demonstrated that WT1 and p53 are present within a
      protein complex in vivo. We now show that WT1 is physically associated with E1B
      55K in adenovirus-transformed cells, an interaction that is mediated by the first
      two zinc fingers of WT1. Immunodepletion of p53 abrogates the
      coimmunoprecipitation of E1B 55K and WT1, consistent with the presence of a
      trimeric protein complex containing these three proteins. In the presence of E1B
      55K, WT1 which is normally localized in the nucleus, is retained within a very
      high molecular weight complex and sequestered in the characteristic perinuclear
      cytoplasmic body that contains E1B 55K and p53. Expression of E1B 55K in
      osteosarcoma cells that undergo apoptosis following expression of WT1 inhibits
      WT1-mediated cell death. We conclude that E1B 55K may target WT1 along with p53,
      resulting in the functional inactivation of both tumor suppressor gene products
      by this viral oncoprotein.

PMID- 9572486
TI  - Cytosol is the prime compartment of hepatitis B virus X protein where it
      colocalizes with the proteasome.
AB  - The hepatitis B virus X protein plays an important role in the regulation of
      viral genome expression and has also been implicated in the development of liver
      cancer associated with chronic viral infection. Several effects have been
      attributed to X but their biological relevance remains elusive. One of the
      confusing issues has been so far the uncertainty concerning its cellular
      location. To gain insight into the mechanism(s) how X exerts its effects, we have
      analysed its subcellular distribution and its dependency on the cell cycle. We
      used two complementary approaches namely, immunolocalization using a cell line
      stably expressing X, and characterization of the dynamics of X location in living
      cells by means of the reporter gene GFP. Our data clearly define the cytosol as
      the prime location of X, irrespectively of the cell cycle and show in addition
      the close attachment of a fraction of X to the nuclear membrane. However, X does
      not associate with any cytoplasmic vesicles and organelles so far tested. In
      contrast, our study provides strong evidence for the codistribution of X with the
      cytosolic fraction of proteasomes. In pulse-chase experiments, X decayed with a
      half-life of less than 30 min and proteasome-inhibitors did not modify its
      turnover, suggesting that X colocalization with the proteasome does not simply
      point to its degradation pathway. The proteolytic processing of the p105
      precursor of the p50 subunit of the NF-kappaB transcription factor, which has
      been shown to be proteasome-dependent, is markedly slow down in the presence of
      X. These findings suggest that X modulates the processing rate of p105 by acting
      presumably at the level of the proteasome. Thus, targeting of proteasomes by X
      might be one of the pathways employed by this viral protein to subvert cellular
      functions.

PMID- 9572487
TI  - The transcription of the intercellular adhesion molecule-1 is regulated by Ets
      transcription factors.
AB  - The Ets family of transcription factors comprises several members which are
      involved to regulate gene transcription. Although several consensus binding sites
      for Ets proteins can be found in a wide series of promoter, only a limited number
      of them are indeed activated by these transcription factors. The human
      intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in immune
      responses by enabling the binding of effector cells to various target cell types.
      ICAM-1 is constitutively expressed at different levels in the absence of stimuli
      in different cell types, and its expression is upregulated by several
      proinflammatory cytokines. We have here examined the transcriptional regulation
      of human ICAM-1 expression by Ets proteins, and more particularly by ERM, a
      member of this family of transcription factors. Transient transfection assays
      revealed that Ets-2 and ERM significantly activate the transcription of ICAM-1
      promoter, whereas the less-related Ets family member, Spi-1/Pu.1, failed to do
      so. Transfection of a series of ICAM-1 promoter deletion mutants together with
      ERM expression plasmids have shown that an Ets responsive element is located
      within the first 176 bp upstream from the translational start site.
      Electrophoretic mobility shift assays and DNase I footprinting analysis have
      enabled us to identify two Ets binding sites at positions -158 and -138 from the
      ATG, respectively. Site directed mutagenesis of these elements has shown that the
      distal site is the major element required for the ERM-mediated activation of the
      ICAM-1 promoter. We can thus conclude that expression of ICAM-1 can be regulated
      by Ets transcription factors.

PMID- 9572488
TI  - Interferon-alpha-induced G1 phase arrest through up-regulated expression of CDK
      inhibitors, p19Ink4D and p21Cip1 in mouse macrophages.
AB  - The mechanism of cell cycle arrest induced by interferon-alpha (IFN-alpha) was
      analysed using a mouse macrophage cell line, BAC1.2F5A. IFN-alpha added in media
      before mid-G1 prohibited cells from entering S phase. The blockage of G1/S
      transition was associated with diminuition of both cyclin D1/cdk4- and cyclin
      E/cdk2-associated kinase activities. G1 cyclin-associated kinase activities were
      down-regulated quickly after the addition of IFN-alpha. Cells treated with IFN
      alpha contained excess amounts of cdk inhibitors which down-regulated G1
      cyclin/cdk-associated kinase activities in the proliferating cells and this
      action was counteracted by exogenously-supplied recombinant cyclin D2/cdk4
      complexes. In parallel, accumulation of p19Ink4D and p21Cip1, and their
      attachment to cdks were up-regulated quickly after the addition of IFN-alpha.
      Expression of p19Ink4D and p21Cip1 was potentiated transcriptionally. We
      concluded that increased attachment of up-regulated cdk inhibitors including
      p19Ink4D and p21Cip1 to G1 cyclin/cdk complexes contributed to diminuition of G1
      cyclin/cdk-associated kinase activities and resulting G1 phase arrest during the
      early phase of treatment with IFN-alpha.

PMID- 9572489
TI  - Overexpression of both p185c-erbB2 and p170mdr-1 renders breast cancer cells
      highly resistant to taxol.
AB  - We recently found that overexpression of p185c-erbB2 in c-erbB2 transfected MDA
      MB-435 breast cancer cells (435.eB transfectants) confers a 5-9-fold increase in
      Taxol resistance. To examine whether Taxol resistance is a common phenomenon in
      other c-erbB2 overexpressing breast cancer cell lines, we tested a panel of human
      breast cancer cell lines established from different patients and expressing pl85c
      erbB2 at different levels for their sensitivity to Taxol and Taxotere, a
      synthetic taxoid. Higher expression of p185c-erbB2 in these breast cancer cell
      lines indeed correlated well with resistance to Taxol and Taxotere, and the
      degree of resistance was about 100-fold that in c-erbB2-overexpressing 435.eB
      transfectants, demonstrating that these breast cancer cells are highly resistant
      to Taxol. Since mdr-1-encoded p-glycoprotein (p170mdr-1) has been implicated in
      Taxol resistance, we next examined the p170mdr-1 levels in these breast cancer
      cell lines that are highly resistant to Taxol. Higher levels of p170mdr-1
      expression were found in several breast cancer cell lines that are highly
      resistant to Taxol. Since these same breast cancer cell lines also expressed
      higher levels of p185c-erbB2, we sought to determine the relative contribution of
      p185c-erbB2 and p170mdr-1 overexpression to Taxol resistance. We first
      specifically down-regulated cell surface p185c-erbB2 using anti-p185c-erbB2
      monoclonal antibodies and assayed sensitivity of these cells to Taxol. We next
      specifically inactivated p170mdr-1 function using p170mdr-1 blockers
      (thioridazine or verapamil) and again assayed Taxol sensitivity. Both p185c-erbB2
      down-regulation and p170mdr-1 blockade significantly sensitized the breast cancer
      cell lines to Taxol. The results indicate that overexpression of either p185c
      erbB2 or p170mdr-1 renders human breast cancer cells resistant to Taxol.
      Furthermore, p185c-erbB2 synergizes with p170mdr-1 conferring higher degrees of
      Taxol resistance. Finally, combination therapy (down-regulation of p185c-erbB2
      plus blocking p170mdr-1 plus administration of Taxol) may be beneficial to breast
      cancer patients whose tumors express high levels of both p185c-erbB2 and p170mdr
      1.

PMID- 9572490
TI  - Epidermal growth factor activation of NF-kappaB is mediated through IkappaBalpha
      degradation and intracellular free calcium.
AB  - The transcription factor NF-kappa-B is normally sequestered in the cytoplasm by
      its inhibitory subunit IkappaB. Most extracellular signals activate NF-kappa-B
      through a mechanism involving the phosphorylation and proteasome-dependent
      degradation of IkappaB. EGF activates NF-kappaB in A-431 carcinoma cells, which
      overexpress EGF receptors and in mouse embryo fibroblasts, which have a normal
      complement of receptors. Supershift experiments indicate that the NF-kappa-B
      complexes induced by EGF are composed of p50/p50 homodimers and p65/p50
      heterodimers, but not c-rel. EGF stimulation enhances the degradation of
      IkappaBalpha, but not IkappaBbeta nor an N-terminal deletion mutant of
      IkappaBalpha. Treatment of cells with a proteasome inhibitor, such as ALLN or
      MG132, blocks EGF-mediated NF-kappaB activation, indicating that EGF-induced NF
      kappa-B activation requires proteasome-dependent IkappaB degradation. Also, Bapta
      A/M (a cell-permeable chelator of intracellular calcium) blocks EGF-induced NF
      kappa-B activation and IkappaBalpha degradation, suggesting a requirement of
      intracellular free Ca2+ for this growth factor response. Protein kinase C
      inhibition, in contrast, did not influence EGF activation of NF-kappaB.

PMID- 9572491
TI  - SV40 T/t-antigen induces premature mammary gland involution by apoptosis and
      selects for p53 missense mutation in mammary tumors.
AB  - We recently established transgenic animals (WAP-SV-T/t) carrying the early coding
      region of Simian Virus 40 (SV40) under the transcriptional control of the whey
      acidic milk protein promoter (WAP), which restricts the expression of the
      transgene to mammary gland epithelial cells (ME-cells). SV40 T/t-antigen
      synthesis causes premature mammary gland involution during late pregnancy by
      inducing apoptosis and leads to development of mammary tumors after the first
      lactation period in both p53 positive (WAP-SV-T/t) and p53 negative double
      transgenic animals (WAP-SV-T/t.p53-/-). The high apoptotic rate persists in all
      of the T/t-antigen positive breast tumor cells, as well as in established ME
      tissue culture cell lines. ME-cells which spontaneously switch off the expression
      of the WAP-SV-T/t transgene do not undergo apoptosis. However, these cells again
      exhibit an extensive DNA fragmentation when SV40 T/t-antigen synthesis is
      reintroduced, which indicates that it is the expression of T/t antigen which is
      the critical factor for induction of apoptosis. In addition, we isolated several
      ME-cell lines from different breast tumors which have spontaneously lost the T/t
      antigen yet remain maximally transformed. Strikingly, these cells contain a
      missense mutation of the p53 gene at codon 242 (p53(242)), which substitutes
      alanine for glycine. This mutation increases p53 stability and it reduces the
      transactivating function of p53, albeit without affecting the ability of the
      protein to interact with the DNA. This indicates that p53 missense mutations are
      selected for in breast tumors initially expressing T/t-antigen. Therefore, the
      p53(242) mutation is sufficient to maintain the transformed state after the ME
      cells have switched off the WAP-SV-T/t transgene. Interestingly, the p53 minus
      state per se is not sufficient to induce ME-cell transformation since homozygous
      null mice for the p53 gene (p53-/-) fail to develop breast cancer.

PMID- 9572492
TI  - p53 mutations isolated in yeast based on loss of transcription factor activity:
      similarities and differences from p53 mutations detected in human tumors.
AB  - p53 is a transcriptional activator that plays a key role in the integration of
      signals inducing cell division arrest and programmed cell death. Moreover, p53 is
      a tumor suppressor gene, mutations of which are the most commonly detected
      mutations in diverse malignancies. In order to better understand the significance
      of p53 mutations to human cancer, we isolated mutant alleles of p53 that had lost
      transcription factor activity in yeast. These mutant alleles were evaluated for
      their precise changes, their activity against three different p53 responsive
      enhancers and their ability to act in a transdominant fashion to the wild type
      allele. While many of the mutations isolated in yeast resembled those found in
      human tumors, consistent with the importance of transcription factor activity for
      p53 in mammalian cells, the mutational spectrum obtained was dependent upon the
      p53 enhancer employed for the selection. Some mutations specifically inactivated
      p53 in yeast for a single enhancer element. Virtually all missense mutations
      tested had a dominant inhibitory effect on wild type p53 in yeast. Since some of
      these transdominant mutations are virtually unknown in human tumors we conclude
      that transdominance, per se, fails to predict which mutations occur frequently in
      cancer.

PMID- 9572493
TI  - Failure of central nervous system myelination in MBP/c-myc transgenic mice:
      evidence for c-myc cytotoxicity.
AB  - c-myc is a member of the helix-loop-helix/leucine zipper family of proteins that
      modulate the transcriptional activity of specific target genes. Although aberrant
      c-myc expression has been reported to play a role in multistage carcinogenesis in
      astrocytic gliomas, little is known about the effects of the expression of c-myc
      on oligodendrocytes. Using transgenic animals expressing a human c-myc oncogene
      under transcriptional control of the myelin basic protein gene, we investigated
      the effect of overexpression of this oncogene in oligodendrocytes. The MBP/c-myc
      transgenic mice developed severe neurological disturbances characterized by
      action tremors and recurrent seizures, and premature death during postnatal weeks
      three to five. Affected transgenic mice of various strains had severely
      hypomyelinated central nervous systems and expressed low levels of c-myc, myelin
      basic protein (MBP) and proteolipid protein (PLP) mRNAs in the brain. These c-myc
      transgenic mice also exhibited an increased number of TUNEL positive nuclei,
      which in most cases were located in cells that expressed c-myc, as judged by
      double immunohistochemistry. There was no evidence of brain tumors in the c-myc
      transgenic mice, including heterozygous mice from two strains that had normal
      lifespans. These observations indicate that the myelin deficiency observed in the
      MBP/c-myc transgenic animals results from a cytotoxic effect of the c-myc
      transgene.

PMID- 9572494
TI  - Defective IkappaBalpha in Hodgkin cell lines with constitutively active NF
      kappaB.
AB  - The molecular mechanisms underlying Hodgkin's disease remain obscure, but it has
      been recognized that the neoplastic cells display high levels of constitutively
      active nuclear NF-kappaB. Here we demonstrate that although nuclear NF-kappaB is
      transcriptionally active, the Hodgkin cells fail to activate NF-kappaB dependent
      transcription in response to CD40 ligand. In three Hodgkin cell lines examined
      each had abnormalities in expression of IkappaBalpha which could account for the
      deregulated NF-kappaB. Although all three cell lines had greater than normal
      levels of IkappaBalpha mRNA no IkappaBalpha protein could be detected in the KM
      H2 cells, while the L428 cell line contains a C-terminally truncated IkappaBalpha
      species that fails to associate with NF-kappaB. The HDLM-2 cell line contains a
      more slowly migrating form of IkappaBalpha that can associate with NF-kappaB, but
      increasing the level of this protein within the cell fails to inhibit nuclear NF
      kappaB. Addition of recombinant IkappaBalpha to nuclear extracts from all three
      cell lines resulted in complete inhibition of NF-kappaB DNA binding activity and
      introduction of a plasmid expressing IkappaBalpha into the cells inhibited the
      transcriptional activity of an NF-kappaB dependent reporter plasmid. Thus the
      constitutive expression of NF-kappaB in Hodgkin cells is a direct consequence of
      the abnormal expression of IkappaBalpha rather than changes in NF-kappaB that
      render it refractory to inhibition by IkappaB proteins. These changes could, at
      least in part, account for the characteristic activated phenotype of Hodgkin
      cells and their pattern of cytokine secretion, which determine the pathological
      appearance and clinical manifestations of Hodgkin's disease.

PMID- 9572495
TI  - Involvement of p21 and p27 in the regulation of CDK activity and cell cycle
      progression in the regenerating liver.
AB  - In tissue culture systems, p21 and p27 inhibit cyclin-dependent kinase (CDK)
      activity and cell cycle progression in response to numerous stimuli, but little
      is known about their involvement in cell growth in vivo. We examined the
      modulation of CDK activity by these proteins after 70% partial hepatectomy (PH),
      an in vivo model of synchronous hepatocyte cell cycle progression. After PH in
      BALB/c mice, p21 was induced during the prereplicative (G1) phase and was
      maximally expressed after peak hepatocyte DNA synthesis. p27 was present in
      quiescent liver and was minimally induced after PH. p21 and p27
      immunoprecipitated with CDK2, CDK4, and cyclin D1 in the regenerating liver. The
      activity of CDK2-, CDK4- and cyclin D1-associated kinases was upregulated after
      PH, and maximal activity of these enzyme complexes corresponded to peak DNA
      synthesis. Immunodepletion experiments suggested that p27 plays a role in
      downregulating CDK2 activity before and after peak DNA synthesis. Compared to
      cogenic wild-type mice, p21-/- mice demonstrated evidence of markedly accelerated
      hepatocyte progression through G1 phase after PH: DNA synthesis, upregulation of
      cyclin A and PCNA, induction of cyclin D1- and CDK2-associated kinase activity,
      and appearance of a phosphorylated retinoblastoma protein (Rb) species occurred
      earlier in the p21-/- mice. These results suggest that p21 and p27 modulate CDK
      activity in the regenerating liver, and that p21 regulates the rate of
      progression through G1 phase of the cell cycle in vivo.

PMID- 9572496
TI  - A GR-motif functions in nuclear accumulation of the large FGF-2 isoforms and
      interferes with mitogenic signalling.
AB  - Nuclear translocation has been documented for members of the fibroblast growth
      factor (FGF) family in addition to their roles as extra-cellular signalling
      molecules. Fusing different parts of the chicken FGF-2 open reading frame to
      pyruvate kinase shows that direct nuclear accumulation is mediated by the amino
      termini of the two leucine initiated FGF-2 isoforms (Leu-isoforms; 21.5 and 20.0
      kDa). An evolutionarily conserved glycine-arginine (GR)-motif is present in the
      21.5 kDa Leu-isoform and a shorter GR-repeat in the 20.0 kDa Leu-isoform, whereas
      no such repeats are present in the 18.5 kDa FGF-2 isoform (Met-isoform).
      Expression in NIH3T3 fibroblasts shows that the 21.5 kDa Leu-isoform is
      predominantly nuclear, whereas the Met-isoform is predominantly cytoplasmic. Most
      importantly, insertion of the GR-motif into the Met-isoform results in a protein
      with characteristics similar to the Leu-isoforms, as shown by nuclear
      accumulation of the chimeric MGR-protein. Furthermore, only NIH3T3 fibroblasts
      expressing the Met-isoform proliferate under serum starvation conditions, whereas
      cells expressing either the MGR- or Leu-isoforms stay growth arrested. These
      studies show that the GR-signal mediates nuclear translocation of endogenous Leu
      isoforms and blocks their mitogenic activity.

PMID- 9572497
TI  - Methylation of the HIC-1 candidate tumor suppressor gene in human breast cancer.
AB  - HIC-1 (hypermethylated in cancer) is a candidate tumor suppressor gene which is
      located at 17p13.3, a region which frequently undergoes allelic loss in breast
      and other human cancers. HIC-1 is proposed to be commonly inactivated in human
      cancers by hypermethylation of a normally unmethylated dense CpG island which
      encompasses the entire gene. To study whether HIC-1 inactivation may be important
      to the development of breast cancer, we first measured methylation of the HIC-1
      gene in normal breast ductal tissues from microdissected frozen breast tissues
      and from epithelial cells purified from mammoplasty specimens. Surprisingly, in
      all normal breast ductal tissues we found approximately equal amounts of densely
      methylated HIC-1 and completely unmethylated HIC-1. This is in contrast to most
      normal tissues, in which all copies of HIC-1 are completely unmethylated. We then
      evaluated 39 primary breast cancer tissues and found virtually complete
      methylation of the HIC-1 gene in 26 (67%) of the cases. We also found loss of
      heterozygosity at the telomeric portion of chromosomal arm 17p in 22 of the 26
      cases with strongly methylated HIC-1, suggesting that loss of an unmethylated HIC
      1 allele may contribute to the inactivation of HIC-1 in cells with a pre-existing
      methylated allele. Finally, by RNase protection analysis, HIC-1 was found to be
      expressed in microdissected normal breast ductal tissues and unmethylated tumors
      but not in tumors with hypermethylation of the HIC-1 gene. These results indicate
      that hypermethylation of HIC-1 and associated loss of HIC-1 expression is common
      in primary breast cancer. Furthermore, the HIC-1 gene is densely methylated in
      approximately one-half of the alleles in normal breast epithelium, which may
      predispose this tissue to inactivation of this gene by loss of heterozygosity.

PMID- 9572498
TI  - Minimal residual cone-beam reconstruction with attenuation correction in SPECT.
AB  - This paper presents an iterative method based on the minimal residual algorithm
      for tomographic attenuation compensated reconstruction from attenuated cone-beam
      projections given the attenuation distribution. Unlike conjugate-gradient based
      reconstruction techniques, the proposed minimal residual based algorithm solves
      directly a quasisymmetric linear system, which is a preconditioned system. Thus
      it avoids the use of normal equations, which improves the convergence rate. Two
      main contributions are introduced. First, a regularization method is derived for
      quasisymmetric problems, based on a Tikhonov-Phillips regularization applied to
      the factorization of the symmetric part of the system matrix. This regularization
      is made spatially adaptive to avoid smoothing the region of interest. Second, our
      existing reconstruction algorithm for attenuation correction in parallel-beam
      geometry is extended to cone-beam geometry. A circular orbit is considered. Two
      preconditioning operators are proposed: the first one is Grangeat's inversion
      formula and the second one is Feldkamp's inversion formula. Experimental results
      obtained on simulated data are presented and the shadow zone effect on attenuated
      data is illustrated.

PMID- 9572500
TI  - A Fourier rebinning algorithm incorporating spectral transfer efficiency for 3D
      PET.
AB  - This paper presents a Fourier rebinning algorithm for three-dimensional image
      reconstruction in PET that incorporates the concept of spectral transfer
      function. It suggests the need for discarding low-frequency components in the
      rebinning. It also includes the correction for rebinning efficiency which was
      evaluated by simulations as a function of oblique angle of projections. The
      performance was optimized by high-pass filters and axial smoothing. The algorithm
      yields satisfactory images with negligible axial cross-talk for a maximum oblique
      angle up to 26.6 degrees. The statistical noise was evaluated in terms of 'noise
      equivalent number of oblique angles', and reasonable results were obtained in
      view of the theoretical expectation. Ring artefacts due to noise are negligibly
      small.

PMID- 9572499
TI  - Iterative reconstruction for helical CT: a simulation study.
AB  - Iterative reconstruction algorithms for helical CT are presented. The algorithms
      are derived from two-dimensional reconstruction algorithms, by adapting the
      projector/backprojector to the helical orbit of the source, and by constraining
      the axial frequencies with a Gaussian sieve. Simulations have been carried out
      and the performance of the iterative algorithms is compared to that of filtered
      backprojection of synthetic (interpolated) two-dimensional sinograms. The
      iterative algorithms produce superior bias-noise curves. Axial resolution is
      superior, but disturbing edge-artefacts are introduced.

PMID- 9572501
TI  - Fast and stable cone-beam filtered backprojection method for non-planar orbits.
AB  - We propose a new cone-beam shift-variant filtered backprojection (FBP) method for
      non-planar orbit data acquisitions. The new method is exact, fast and stable to
      discretization errors. It is based on the hybrid FBP framework whose key feature
      is to combine the shift-variant filtering with the ramp filtering to produce the
      filtered projections. We show that an adequate combination of the two filterings
      allows us to minimize contributions of the time-consuming and numerically
      unstable shift-variant filtering. We demonstrate the performances of the new
      method by simulation studies. We also apply the new method to real x-ray data
      acquired from our experimental system of monochromatic computed tomography.

PMID- 9572502
TI  - An analytic model of pinhole aperture penetration for 3D pinhole SPECT image
      reconstruction.
AB  - Photons penetrate the attenuating material close to the aperture of pinhole
      collimators in nuclear medicine, broadening the tails of point spread functions
      (PSFs) and degrading the resolution of planar and SPECT images. An analytic
      approximation has been developed that models this penetration contribution to the
      PSF for knife-edge point pinhole apertures. The approximation has the form exp(
      gamma r), where r is the distance on the detector surface from the projection of
      the point source through the pinhole. The rolloff coefficient gamma is a function
      of the photon energy, point source location and the design parameters of the
      collimator. There was excellent agreement between measured values of gamma from
      photon transport simulations of I-131 point sources (364 keV emission only) and
      theoretical predictions from the analytic formula. Predicted gamma values from
      the analytic formula averaged 25% greater than measured values from experimental
      I-131 point source acquisitions. Photon transport simulations were performed that
      modelled the 364 keV and less abundant 637 and 723 keV emissions and scatter
      within the scintillation crystal. Measured gamma values from these simulations
      averaged 12% greater than the experimental values, indicating that about half of
      the error between the analytic formula and the experimental measurements was due
      to unmodelled 637 and 723 keV emissions. The remaining error may be due in part
      to scatter in the pinhole region and backscatter from gamma camera components
      behind the scintillation crystal. The analytic penetration model was used in
      designing Metz filters to compensate for penetration blur and these filters were
      applied to the projection data as part of 3D SPECT image reconstruction. Image
      resolution and contrast were improved in simulated and experimental I-131 tumour
      phantom studies. This analytic model of pinhole aperture penetration can be
      readily incorporated into iterative 3D SPECT pinhole reconstruction algorithms.

PMID- 9572503
TI  - Experience with fully 3D PET and implications for future high-resolution 3D
      tomographs.
AB  - The aim of this paper is to report on experience with 3D positron emission
      tomography (PET) in our institute where we have three 3D scanners, of which two
      operate exclusively in 3D mode (ECAT ART, EXACT 3D). Fully 3D PET requires
      attention to a number of factors which are not as problematic in 2D PET. Firstly,
      3D tomographs designed for whole-body acquisition suffer from a large single
      photon field of view, extending well beyond the coincidence field of view. Single
      photons from outside the coincidence field of view increase the dead time and
      random coincidence rates, and contribute scattered events. For brain studies, we
      have extended the lead side shielding at the ends of the tomograph to mitigate
      against these effects, and this has dramatically improved the count rate
      performance. This approach is not as effective for whole-body scanning. In
      addition, operating in 3D without septa necessitates new approaches to
      transmission scanning, as measurements using positron emitters such as 68Ge/68Ga
      have the unfavourable characteristics of high dead time and high scatter. Both of
      our fully 3D scanners use 137Cs for single-photon transmission measurements,
      although the data are treated differently. On the ECAT ART, a combination of
      physical and electronic collimation effectively reduces transmission scatter to
      acceptable levels. On the EXACT 3D physical collimation is not as readily
      implemented and therefore segmentation and reassignment of the histogrammed
      attenuation (mu) values is employed to produce unbiased attenuation correction
      factors in 3D. Many of the lessons learnt with these BGO (bismuth germanate)
      based tomographs will be applicable to the next generation of systems using
      faster detectors such as lutetium oxyorthosilicate (LSO).

PMID- 9572504
TI  - Performance of the Fourier rebinning algorithm for PET with large acceptance
      angles.
AB  - The recently proposed Fourier rebinning (FORE) technique of 3D PET reconstruction
      is investigated over a wide range of axial acceptance angles. In this study we
      evaluate the performance of the FORE technique using spatial resolution, contrast
      and noise figures of merit and compare reconstruction performance of the FORE
      (followed by multislice 2D reconstruction) to the 3D-RP technique for large
      acceptance-angle data (+/-26.25 degrees). Our results show that the FORE
      technique does not affect the transverse resolution. On the other hand the axial
      resolution using FORE deteriorates faster, compared with the 3D-RP, at large
      radii as the acceptance angle increases. Concerning the noise behaviour, we have
      found that filtering has better ability to suppress the noise in the FORE
      reconstruction, compared with the 3D-RP reconstruction, especially in the slices
      near the edge of the axial field of view. Overall, the combination of good
      performance and fast reconstruction time makes the FORE technique a practical
      choice for 3D PET applications.

PMID- 9572505
TI  - The dual-ellipse cross vertex path for exact reconstruction of long objects in
      cone-beam tomography.
AB  - We investigate the way data are used in the algorithm proposed by Kudo and Saito
      for the exact reconstruction of long objects from axially truncated cone-beam
      projections. Specifically, we show that the algorithm wastes a large part of the
      data. To overcome the problem, we propose to use a vertex path consisting of two
      crossing ellipses, for which we devised a new reconstruction algorithm, called
      the cross algorithm, which does not waste data and is still suitable to exactly
      handle axial truncation. Results of reconstruction are presented on simulated
      data and real data from an experimental scanner.

PMID- 9572506
TI  - Iterative and analytical reconstruction algorithms for varying-focal-length cone
      beam projections.
AB  - In single photon emission computed tomography (SPECT), a varying-focal-length
      cone-beam collimator can be used to reduce the truncation problem and to maintain
      sensitivity when imaging the organ of interest. The collimator is constructed so
      that the collimator holes focus to a circular symmetric, spatially varying, focal
      point function. The focal length increases radially from the shortest focal
      length at the centre to the longest focal length at the periphery of the
      collimator. This paper describes a 3D backprojection-filtering (BF) algorithm for
      this varying-focal-length cone-beam geometry. The proposed algorithm is compared
      to an iterative ML-EM (maximum likelihood-expectation maximization) algorithm.
      The 3D Hoffman brain phantom and Defrise phantom are used in computer
      simulations. Since the maximum tilt angle of the projection rays is small for
      most realistic imaging geometries, the proposed algorithm provides a good
      approximation. When a circular orbit is used, the BF algorithm gives an exact
      reconstruction of the central slice.

PMID- 9572508
TI  - Fast accurate iterative reconstruction for low-statistics positron volume
      imaging.
AB  - A fast accurate iterative reconstruction (FAIR) method suitable for low
      statistics positron volume imaging has been developed. The method, based on the
      expectation maximization-maximum likelihood (EM-ML) technique, operates on list
      mode data rather than histogrammed projection data and can, in just one pass
      through the data, generate images with the same characteristics as several ML
      iterations. Use of list-mode data preserves maximum sampling accuracy and
      implicitly ignores lines of response (LORs) in which no counts were recorded. The
      method is particularly suited to systems where sampling accuracy can be lost by
      histogramming events into coarse LOR bins, and also to sparse data situations
      such as fast whole-body and dynamic imaging where sampling accuracy may be
      compromised by storage requirements and where reconstruction time can be wasted
      by including LORs with no counts. The technique can be accelerated by operating
      on subsets of list-mode data which also allows scope for simultaneous data
      acquisition and iterative reconstruction. The method is compared with a standard
      implementation of the EM-ML technique and is shown to offer improved resolution,
      contrast and noise properties as a direct result of using improved spatial
      sampling, limited only by hardware specifications.

PMID- 9572507
TI  - Intercomparison of four reconstruction techniques for positron volume imaging
      with rotating planar detectors.
AB  - Four reconstruction techniques for positron volume imaging have been evaluated
      for scanners based on rotating planar detectors using measured and simulated
      data. The four techniques compared are backproject then filter (BPF), the 3D
      reprojection (3D RP) method for 3D filtered backprojection (FBP), Fourier
      rebinning (FORE) in conjunction with 2D FBP (FORE + 2D FBP) and 3D ordered
      subsets expectation maximization (3D OSEM). The comparison was based on image
      resolution and on the trade-off between contrast and noise. In general FORE + 2D
      FBP offered a better contrast-noise trade-off than 3D RP, whilst 3D RP offered a
      better trade-off than BPF. Unlike 3D RP, FORE + 2D FBP did not suffer any
      contrast degradation effect at the edges of the axial field of view, but was
      unable to take as much advantage from high-accuracy data as the other methods. 3D
      OSEM gave the best contrast at the expense of greater image noise. BPF, which
      demonstrated generally inferior contrast-noise behaviour due to use of only a
      subset of the data, gave more consistent spatial resolution over the field of
      view than the projection-data based methods, and was best at taking full
      advantage of high-accuracy data.

PMID- 9572509
TI  - High-helical-pitch, cone-beam computed tomography.
AB  - The object of a helical, cone-beam computed tomography, HCBCT, system is faster
      scan times for the volume of interest for a patient. The maximum helical-pitch
      that still produces good quality images limits the reduction in scan time.
      Although this is a three-dimensional problem, an extension of the completeness
      condition for a two-dimensional fan-beam reconstruction method serves as a guide
      to estimate the maximum helical-pitch. In HCBCT, each pixel in an arbitrary image
      slice is irradiated over a different range of gantry rotation angles. This leads
      to the idea of a different, or inconsistent, range of backprojection angles for
      each pixel in order to increase the helical-pitch while satisfying the
      completeness condition. Using inconsistent backprojection, the normalized helical
      pitch ratio increases from 0.90 to 1.40 (for a source radius of 600 mm and field
      of view of 500 mm), where the normalized helical-pitch ratio is the linear
      advance of the patient couch per gantry revolution to the full axial height of
      the area detector (as projected at the isocentre).

PMID- 9572510
TI  - Fast implementations of reconstruction-based scatter compensation in fully 3D
      SPECT image reconstruction.
AB  - Accurate scatter compensation in SPECT can be performed by modelling the scatter
      response function during the reconstruction process. This method is called
      reconstruction-based scatter compensation (RBSC). It has been shown that RBSC has
      a number of advantages over other methods of compensating for scatter, but using
      RBSC for fully 3D compensation has resulted in prohibitively long reconstruction
      times. In this work we propose two new methods that can be used in conjunction
      with existing methods to achieve marked reductions in RBSC reconstruction times.
      The first method, coarse-grid scatter modelling, significantly accelerates the
      scatter model by exploiting the fact that scatter is dominated by low-frequency
      information. The second method, intermittent RBSC, further accelerates the
      reconstruction process by limiting the number of iterations during which scatter
      is modelled. The fast implementations were evaluated using a Monte Carlo
      simulated experiment of the 3D MCAT phantom with 99mTc tracer, and also using
      experimentally acquired data with 201Tl tracer. Results indicated that these fast
      methods can reconstruct, with fully 3D compensation, images very similar to those
      obtained using standard RBSC methods, and in reconstruction times that are an
      order of magnitude shorter. Using these methods, fully 3D iterative
      reconstruction with RBSC can be performed well within the realm of clinically
      realistic times (under 10 minutes for 64 x 64 x 24 image reconstruction).

PMID- 9572511
TI  - Block-iterative techniques for fast 4D reconstruction using a priori motion
      models in gated cardiac SPECT.
AB  - We introduce a fast block-iterative maximum a posteriori (MAP) reconstruction
      algorithm and apply it to four-dimensional reconstruction of gated SPECT
      perfusion studies. The new algorithm, called RBI-MAP, is based on the rescaled
      block iterative EM (RBI-EM) algorithm. We develop RBI-MAP based on similarities
      between the RBI-EM, ML-EM and MAP-EM algorithms. RBI-MAP requires far fewer
      iterations than MAP-EM, and so should result in acceleration similar to that
      obtained from using RBI-EM or OS-EM as opposed to ML-EM. When complex four
      dimensional clique structures are used in the prior, however, evaluation of the
      smoothing prior dominates the processing time. We show that a simple scheme for
      updating the prior term in the heart region only for RBI-MAP results in savings
      in processing time of a factor of six over MAP-EM. The RBI-MAP algorithm
      incorporating 3D collimator-detector response compensation is demonstrated on a
      simulated 99mTc gated perfusion study. Results of RBI-MAP are compared with RBI
      EM followed by a 4D linear filter. For the simulated study, we find that RBI-MAP
      provides consistently higher defect contrast for a given degree of noise
      smoothing than does filtered RBI-EM. This is an indication that RBI-MAP smoothing
      does less to degrade resolution gained from 3D detector response compensation
      than does a linear filter. We conclude that RBI-MAP can provide smooth four
      dimensional reconstructions with good visualization of heart structures in
      clinically realistic processing times.

PMID- 9572512
TI  - Application of spherical harmonics to image reconstruction for the Compton
      camera.
AB  - The Compton camera can collect SPECT data with high efficiency due to electronic
      collimation. The data acquired from a Compton camera are projections of source
      activity along cones and are approximated in this paper by cone-surface
      integrals. This paper proposes the use of an orthogonal spherical expansion to
      convert the cone-surface integrals into plane integrals. The conversion technique
      is efficient. Once the plane integrals are obtained, a 3D image can be
      reconstructed by the 3D Radon inversion formula. The algorithm is implemented and
      computer simulations are used to demonstrate the efficiency and accuracy of the
      proposed reconstruction algorithm.

PMID- 9572513
TI  - The effect of activity outside the direct field of view in a 3D-only whole-body
      positron tomograph.
AB  - The ECAT EXACT3D (CTI/Siemens 966) 3D-only PET tomograph has unprecedented
      sensitivity due to the large BGO (bismuth germanate) detector volume. However,
      the consequences of a large (23.4 cm) axial field-of-view (FOV) and the need for
      a patient port diameter to accommodate body scanning make the device more
      sensitive to photons arising from activity outside the direct (coincidence) FOV.
      This leads to relatively higher deadtime and an increased registration of random
      and scatter (true) coincidences. The purpose of this study is to determine the
      influence of activity outside the FOV on (i) noise-equivalent counts (NEC) and
      (ii) the performance of a 'model-based' scatter correction algorithm, and to
      investigate the effect of side shielding additional to that supplied with the
      tomograph. Annular shielding designed for brain scanning increased the NEC for
      blood flow (H[2]15O) measurement (integrated over 120 s) by up to 25%. For 11C
      tracer studies, the increase is less than 5% over 120 min. Purpose-built
      additional body shielding, made to conform to the shape of a volunteer, reduced
      the randoms count rate in a heart blood flow measurement (H[2]15O) by about 30%.
      After scatter correction the discrepancy between ROI count ratios for
      compartments within the 20 cm diameter 'Utah' phantom differed by less than 5%
      from true (sampled) activity concentration ratios. This was so with or without
      activity outside the FOV and with or without additional side shielding. Count
      rate performance is thus improved by extra shielding but more improvement is seen
      in head than in body scanning. Measurement of heart blood flow using bolus
      injections of H(2)15O would benefit from the use of detectors with lower deadtime
      and superior timing resolution such as LSO (lutetium oxyorthosilicate).

PMID- 9572514
TI  - Quantitative cardiac SPECT in three dimensions: validation by experimental
      phantom studies.
AB  - A mathematical framework for quantitative SPECT (single photon emission computed
      tomography) reconstruction of the heart is presented. An efficient simultaneous
      compensation approach to the reconstruction task is described. The implementation
      of the approach on a digital computer is delineated. The approach was validated
      by experimental data acquired from chest phantoms. The phantoms consisted of a
      cylindrical elliptical tank of Plexiglass, a cardiac insert made of Plexiglass, a
      spine insert of packed bone meal and lung inserts made of styrofoam beads alone.
      Water bags were added to simulate different body characteristics. Comparison
      between the quantitative reconstruction and the conventional FBP (filtered
      backprojection) method was performed. The FBP reconstruction had a poor
      quantitative accuracy and varied for different body configurations. Significant
      improvement in reconstruction accuracy by the quantitative approach was
      demonstrated with a moderate computing time on a currently available desktop
      computer. Furthermore, the quantitative reconstruction was robust for different
      body characteristics. Therefore, the quantitative approach has the potential for
      clinical use.

PMID- 9572515
TI  - Axial slice width in 3D PET: characterization and potential improvement with
      axial interleaving.
AB  - The axial slice width for the GE Advance PET scanner has previously been reported
      to be worse for 3D acquisitions than for 2D. The goals of this study were to
      investigate the source(s) of this observed difference and to assess whether the
      3D axial slice width could be significantly improved by acquisition and
      simultaneous reconstruction of axially interleaved data. The axial slice width
      was measured for the three acquisition modes of the Advance scanner ('standard'
      high-sensitivity 2D, high-resolution 2D and 3D), with the septa both extended and
      retracted. A significant degradation in the axial slice width for 3D compared
      with that for high-sensitivity 2D mode was seen. Near the centre, this difference
      can largely be attributed to septa collimation effects of the 2D data. At larger
      radial positions, axial mispositioning of cross-coincidences in 2D acquisitions
      overshadows the effects of septa collimation, while 3D reconstruction effects
      also become more important. The axial slice width was estimated to improve by 0.3
      1.1 mm with interleaving. This modest improvement would be accompanied by an
      increase in image noise, since an axial filter with a higher cut-off would be
      required in the 3D reconstruction to achieve this resolution in the image.

PMID- 9572516
TI  - Feldkamp and circle-and-line cone-beam reconstruction for 3D micro-CT of vascular
      networks.
AB  - Detailed morphometric knowledge of the microvascular network is needed for
      studies relating structure to haemodynamic function in organs like the lung.
      Clinical volumetric CT is limited to millimetre-order spatial resolution. Since
      evidence suggests that small arterioles (50 to 300 micrometres) dominate
      pulmonary haemodynamics, we built a micro-CT scanner, capable of imaging excised
      lungs in 3D with 100 microm resolution, for basic physiology research. The
      scanner incorporates a micro-focal (3 microm) x-ray source, an xyz theta stage
      and a CCD-coupled image intensifier detector. We imaged phantoms and contrast
      enhanced rat lungs, reconstructing the data with either the Feldkamp or the
      circle-and-line cone-beam reconstruction algorithm. We present reconstructions
      using 180 views over 360 degrees for the circular trajectory, augmented with
      views from a linear scan for the circle-and-line algorithm. Especially for
      platelike features perpendicular to the rotation axis and remote from the
      midplane, the circle-and-line algorithm produces superior reconstructions
      compared with Feldkamp's algorithm. We conclude that the use of nonplanar source
      trajectories to perform micro-CT on contrast-enhanced, excised lungs can provide
      data useful for morphometric analysis of vascular trees, currently down to the
      130 microm level.

PMID- 9572517
TI  - Improved estimation of the detector response function for converging beam
      collimators.
AB  - Converging beam collimator geometries offer improved tradeoffs between resolution
      and noise for single photon emission computed tomography (SPECT). The major
      factor limiting the resolution in SPECT is the collimator-detector response
      blurring. In order to compensate for this blurring it is useful to be able to
      calculate the collimator response function. A previous formulation presented a
      method for calculating the response for parallel and converging beam collimators
      that assumed that the shape of the holes did not change over the face of the
      collimator. However, cast collimators are fabricated using pins with a constant
      cross-section (shape perpendicular to the pin axis). As a result, due to the
      angulation of the pins, the holes made by these pins have shapes on the front and
      back faces of the collimator that change with position. This change in hole shape
      is especially pronounced when the angle between the collimator hole and the
      collimator normal is large, as is the case for half-fan-beam or short-focal
      length collimators. This paper presents a derivation of a modification to the
      original method that accounts for the change in shape of the collimator holes.
      The method has been verified by comparing predicted line spread functions to
      experimentally measured ones for a collimator with a maximum hole angle of 35
      degrees with respect to the normal. This formulation is useful for predicting the
      response of fan-beam collimators in the design process and for use in detector
      response compensation algorithms.

PMID- 9572518
TI  - Three-dimensional reconstruction from cone-beam data using an efficient Fourier
      technique combined with a special interpolation filter.
AB  - We here present LINCON(FAST) which is an exact method for 3D reconstruction from
      cone-beam projection data. The new method is compared to the LINCON method which
      is known to be fast and to give good image quality. Both methods have O(N3 log N)
      complexity and are based on Grangeat's result which states that the derivative of
      the Radon transform of the object function can be obtained from cone-beam
      projections. One disadvantage with LINCON is that the rather computationally
      intensive chirp z-transform is frequently used. In LINCON(FAST), FFT and
      interpolation in the Fourier domain are used instead, which are less
      computationally demanding. The computation tools involved in LINCON(FAST) are
      solely FFT, 1D eight-point interpolation, multiplicative weighting and tri-linear
      interpolation. We estimate that LINCON(FAST) will be 2-2.5 times faster than
      LINCON. The interpolation filter belongs to a special class of filters developed
      by us. It turns out that the filter must be very carefully designed to keep a
      good image quality. Visual inspection of experimental results shows that the
      image quality is almost the same for LINCON and the new method LINCON(FAST).
      However, it should be remembered that LINCON(FAST) can never give better image
      quality than LINCON, since LINCON(FAST) is designed to approximate LINCON as well
      as possible.

PMID- 9572519
TI  - Normalization for 3D PET with a low-scatter planar source and measured geometric
      factors.
AB  - For 3D PET normalization methods, a balance must be struck between statistical
      accuracy and individual detector or line-of-response (LOR) fidelity. Methods with
      potentially the best LOR accuracy tend to be statistically poor, while techniques
      to improve the statistical quality tend to reduce the individual detector
      fidelity. We have developed and implemented a 3D PET normalization method for our
      ECAT 953B scanner (Siemens/CTI) that determines the detector normalization
      factors (NFs) as a product of a four-dimensional matrix of measured geometric
      factors (GFs) and single detector efficiency factors (epsilon). The effects of
      various alterations to the algorithm on the accuracy of the normalization have
      been examined through the impact on reconstructed images. An accurate set of GFs
      is crucial, as inaccurate NFs can result if LORs with similar but not identical
      geometric symmetries are grouped together. The general method can be extended to
      other tomographs, although the dimensionality of a GF matrix may be scanner
      specific; the key is to determine the optimal number of dimensions in the GF
      matrix. The GFs for our scanner are specified by: (i) the two detector rings for
      each LOR; (ii) the radial distance of the LOR from the tomograph centre; and
      (iii) the positions within the detector block of the two crystals defining the
      LOR. Some residual radial non-uniformities are present in all the NF variations
      we examined. For the NF method presented here, the radial non-uniformities are
      attributed to the interaction between object-dependent scatter and normalization.
      Results indicate that this non-uniformity is detectable for scans with as few as
      13 million total counts.

PMID- 9572520
TI  - Kinetic parameter estimation from SPECT cone-beam projection measurements.
AB  - Kinetic parameters are commonly estimated from dynamically acquired nuclear
      medicine data by first reconstructing a dynamic sequence of images and
      subsequently fitting the parameters to time-activity curves generated from
      regions of interest overlaid upon the image sequence. Biased estimates can result
      from images reconstructed using inconsistent projections of a time-varying
      distribution of radiopharmaceutical acquired by a rotating SPECT system. If the
      SPECT data are acquired using cone-beam collimators wherein the gantry rotates so
      that the focal point of the collimators always remains in a plane, additional
      biases can arise from images reconstructed using insufficient, as well as
      truncated, projection samples. To overcome these problems we have investigated
      the estimation of kinetic parameters directly from SPECT cone-beam projection
      data by modelling the data acquisition process. To accomplish this it was
      necessary to parametrize the spatial and temporal distribution of the
      radiopharmaceutical within the SPECT field of view. In a simulated chest image
      volume, kinetic parameters were estimated for simple one-compartment models for
      four myocardial regions of interest. Myocardial uptake and washout parameters
      estimated by conventional analysis of noiseless simulated cone-beam data had
      biases ranging between 3-26% and 0-28%, respectively. Parameters estimated
      directly from the noiseless projection data were unbiased as expected, since the
      model used for fitting was faithful to the simulation. Statistical uncertainties
      of parameter estimates for 10,000,000 events ranged between 0.2-9% for the uptake
      parameters and between 0.3-6% for the washout parameters.

PMID- 9572521
TI  - Tomographic reconstruction using 3D deformable models.
AB  - We address the issue of reconstructing the shape of an object with uniform
      interior activity from a set of projections. We estimate directly from projection
      data the position of a triangulated surface describing the boundary of the object
      while incorporating prior knowledge about the unknown shape. This inverse problem
      is addressed in a Bayesian framework using the maximum a posteriori (MAP)
      estimate for the reconstruction. The derivatives needed for the gradient-based
      optimization of the model parameters are obtained using the adjoint
      differentiation technique. We present results from a numerical simulation of a
      dynamic cardiac imaging study. A first-pass exam is simulated with a numerical
      phantom of the right ventricle using the measured system response of the
      University of Arizona FASTSPECT imager, which consists of 24 detectors. We
      demonstrate the usefulness of our approach by reconstructing the shape of the
      ventricle from 10,000 counts. The comparison with an ML-EM result shows the
      usefulness of the deformable model approach.

PMID- 9572522
TI  - Combined constraints for efficient algebraic regularized methods in fully 3D
      reconstruction.
AB  - SPECT systems incorporate the use of one or more rotating gamma cameras which can
      be equipped with cone-beam collimators to improve the trade-off between spatial
      resolution and sensitivity. The geometry of the cone-beam collimators implies
      that a specific 3D reconstruction algorithm must be applied. Algebraic methods
      provide the possibility of including the physical characteristics, such as
      attenuation, Compton scatter and detector response, in the reconstruction
      process. However, the reconstruction problem is an ill-posed problem which should
      be regularized. This paper presents a 3D algebraic method that combines three
      regularizing constraints. These constraints deal respectively with penalizing
      negative voxels, local noise smoothing and missing data compensation. The results
      presented were obtained from imaging simulations, phantom data and from a thyroid
      clinical study of a normal volunteer.

PMID- 9572523
TI  - High-resolution 3D Bayesian image reconstruction using the microPET small-animal
      scanner.
AB  - A Bayesian method is described for reconstruction of high-resolution 3D images
      from the microPET small-animal scanner. Resolution recovery is achieved by
      explicitly modelling the depth dependent geometric sensitivity for each voxel in
      combination with an accurate detector response model that includes factors due to
      photon pair non-collinearity and inter-crystal scatter and penetration. To reduce
      storage and computational costs we use a factored matrix in which the detector
      response is modelled using a sinogram blurring kernel. Maximum a posteriori (MAP)
      images are reconstructed using this model in combination with a Poisson
      likelihood function and a Gibbs prior on the image. Reconstructions obtained from
      point source data using the accurate system model demonstrate a potential for
      near-isotropic FWHM resolution of approximately 1.2 mm at the center of the field
      of view compared with approximately 2 mm when using an analytic 3D reprojection
      (3DRP) method with a ramp filter. These results also show the ability of the
      accurate system model to compensate for resolution loss due to crystal
      penetration producing nearly constant radial FWHM resolution of 1 mm out to a 4
      mm radius. Studies with a point source in a uniform cylinder indicate that as the
      resolution of the image is reduced to control noise propagation the resolution
      obtained using the accurate system model is superior to that obtained using 3DRP
      at matched background noise levels. Additional studies using pie phantoms with
      hot and cold cylinders of diameter 1-2.5 mm and 18FDG animal studies appear to
      confirm this observation.

PMID- 9572524
TI  - Exact cone beam CT with a spiral scan.
AB  - A method is developed which makes it possible to scan and reconstruct an object
      with cone beam x-rays in a spiral scan path with area detectors much shorter than
      the length of the object. The method is mathematically exact. If only a region of
      interest of the object is to be imaged, a top circle scan at the top level of the
      region of interest and a bottom circle scan at the bottom level of the region of
      interest are added. The height of the detector is required to cover only the
      distance between adjacent turns in the spiral projected at the detector. To
      reconstruct the object, the Radon transform for each plane intersecting the
      object is computed from the totality of the cone beam data. This is achieved by
      suitably combining the cone beam data taken at different source positions on the
      scan path; the angular range of the cone beam data required at each source
      position can be determined easily with a mask which is the spiral scan path
      projected on the detector from the current source position. The spiral scan
      algorithm has been successfully validated with simulated cone beam data.

PMID- 9572525
TI  - Comparison of frequency-distance relationship and Gaussian-diffusion-based
      methods of compensation for distance-dependent spatial resolution in SPECT
      imaging.
AB  - The goal of this investigation was to compare resolution recovery versus noise
      level of two methods for compensation of distance-dependent resolution (DDR) in
      SPECT imaging. The two methods of compensation were restoration filtering based
      on the frequency-distance relationship (FDR) prior to iterative reconstruction,
      and modelling DDR in the projector/backprojector pair employed in iterative
      reconstruction. FDR restoration filtering was computationally faster than
      modelling the detector response in iterative reconstruction. Using Gaussian
      diffusion to model the detector response in iterative reconstruction sped up the
      process by a factor of 2.5 over frequency domain filtering in the
      projector/backprojector pair. Gaussian diffusion modelling resulted in a better
      resolution versus noise tradeoff than either FDR restoration filtering or solely
      modelling attenuation in the projector/backprojector pair of iterative
      reconstruction. For the pixel size investigated herein (0.317 cm), accounting for
      DDR in the projector/backprojector pair by Gaussian diffusion, or by applying a
      blurring function based on the distance from the face of the collimator at each
      distance, resulted in very similar resolution recovery and slice noise level.

PMID- 9572526
TI  - Symmetry properties of an imaging system and consistency conditions in image
      space.
AB  - A general definition for a symmetry group of an imaging system is given. A key
      requirement is that the operators that represent the symmetries in data space are
      conformal. The result is that the space of consistency conditions is invariant
      under the action of the given symmetry group. Via the theory of group
      representations, this fact provides information about the possible forms that
      these consistency conditions can take. The theory is illustrated by example for
      the 2D and 3D Radon transforms, the cone-beam transform on a circular orbit and
      the 2D attenuated Radon transform.

PMID- 9572527
TI  - Pineal opioid receptors and analgesic action of melatonin.
AB  - Physicians have noted since antiquity that their patients complained of less pain
      and required fewer analgesics at night times. In most species, including the
      humans, the circulating levels of melatonin, a substance with analgesic and
      hypnotic properties, exhibit a pronounced circadian rhythm with serum levels
      being high at night and very low during day times. Moreover, melatonin exhibits
      maximal analgesic effects at night, pinealectomy abolishes the analgesic effects
      of melatonin, and mu opioid receptor antagonists disrupt the day-night rhythm of
      nociception. It is believed that melatonin, with its sedative and analgesic
      effects, is capable of providing a pain free sleep so that the body may
      recuperate and restore itself to function again at its peak capacity. Moreover,
      in conditions when pain is associated with extensive tissue injury, melatonin's
      ability to scavenge free radicals and abort oxidative stress is yet another
      beneficial effect to be realized. Since melatonin may behave as a mixed opioid
      receptor agonist-antagonist, it is doubtful that a physician simply could
      potentiate the analgesic efficacy of narcotics such as morphine by
      coadministering melatonin. Therefore, future research may synthesize highly
      efficacious melatonin analogues capable of providing maximum analgesia and
      hopefully being devoid of addiction liability now associated with currently
      available narcotics.

PMID- 9572528
TI  - Existence and function of opioid receptors on mammalian pinealocytes.
AB  - Previous studies in our laboratories have identified a single population of
      opioid receptors in bovine pineal gland, which we have chosen to characterize
      further on pinealocytes isolated from the cow and rat pineal gland. The bovine
      pinealocytes isolated by trypsinization or mechanical manipulation revealed
      receptor density (Bmax) values of 206.95 +/- 131.15 and 220.34 +/- 11.80 fmol/mg
      protein, respectively, and dissociation equilibrium constant (Kd) values of 1.93
      +/- 0.48 and 1.96 +/- 0.21 nM, respectively. The rat pinealocytes cultured for 7
      days exhibited a [3H]diprenorphine binding site of 56 fmol/10(6) cells. Morphine
      (100 microM) enhanced the activity of N-acetyltransferase and the level of
      melatonin in rat pineal gland in culture incubated for 21 hr. The results of
      these studies suggest that opioidergic receptors exist on pinealocytes and they
      are involved in stimulating the activity of N-acetyltransferase and the synthesis
      of melatonin, thereby regulating the physiology of mammalian pineal gland.

PMID- 9572529
TI  - Opioidergic innervation of the tree shrew pineal gland: an immunohistochemical
      study.
AB  - The tree shrew (Tupaia glis) has been described as a missing link relating
      primate to insectivore stock. The pineal gland of the tree shrew consists of a
      superficial pineal and a deep pineal, which are connected by a long and slender
      pineal stalk. A monoclonal antibody against leu-enkephalin was used in an
      immunohistochemical investigation of the tree shrew pineal gland. A moderate
      innervation of leu-enkephalin immunoreactive nerve fibers has been demonstrated
      in both superficial and deep pineal gland of the tree shrew. The density of the
      nerve fibers was slightly higher in the superficial pineal than that of the deep
      one. The number of immunoreactive nerve fibers were observed in the capsule of
      the pineal gland from where they entered the pineal parenchyma. Only a few
      immunoreactive fibers were found in the habenular area and the area rostral to
      the pineal recess, connecting the habenula and the deep pineal. Furthermore, some
      positive fibers were located in the pineal stalk. There was no evidence of leu
      enkephalin immunoreactive intrapineal cells as seen in the other species of
      mammal. Therefore, the interspecies variation of opioidergic innervation among
      the mammals may exist. The lack of intrapineal perikarya is interpreted to
      indicate that the sources of leu-enkephalin nerve fibers were outside the gland.
      The anatomical location of the leu-enkephalin immunoreactive nerve fibers in the
      tree shrew pineal gland supports to both central and peripheral pinealopetal
      pathways in this species.

PMID- 9572530
TI  - Anticonvulsant activity of melatonin against seizures induced by quinolinate,
      kainate, glutamate, NMDA, and pentylenetetrazole in mice.
AB  - Melatonin was tested in an ongoing attempt to find the endogenous antagonists of
      quinolinic acid, an endogenous convulsant. Among a great number of metabolites
      that have been tried before, only a few were found (cerulein and quinaldic acid
      in mice and kynurenic acid in rats). In SHR (bred from Swiss) male mice,
      intracerebroventricular (i.c.v.) pretreatment with melatonin (1.25-10.0 microg)
      attenuated (in the descending order of potency) the convulsant effect of i.c.v.
      administered kainate, quinolinate, glutamate, N-methyl-D-aspartate, and
      pentylenetetrazole. Melatonin was ineffective against i.p. administered
      pentylenetetrazole. Systemically (intraperitoneal, i.p.) administered melatonin
      (12.5-100.0 mg/kg) attenuated the convulsant effect of quinolinate, while the
      action of other convulsants used remained unaltered. It is suggested that
      melatonin could be tried against grand mal seizures in epileptic patients.

PMID- 9572531
TI  - Modulation of plasma melatonin concentrations by changes in posture.
AB  - Posture change from a lying position to a standing position results in a decrease
      in plasma volume, which leads to an increase in plasma constituents, especially
      that of proteins and blood constituents bound to them. The aim of the present
      study was to investigate the physiological effects of postural changes on plasma
      nocturnal melatonin concentrations in healthy human volunteers. The study was
      divided into four stages. During stage one, subjects were seated from 21.00 hr to
      01.00 hr. In stage two, subjects were lying at ground level from 21.00 hr to
      01.00 hr. In stage three, subjects were is a sitting position from 2100 hr to
      2300 hr and then in a standing position from 23.00 hr to 24.00 hr, and back to
      the sitting position from 24.00 hr to 01.00 hr. In the final stage, subjects were
      in a lying position from 21.00 hr to 23.00 hr and then in a standing position
      from 23.00 hr to 24.00 hr and back to the lying position from 24.00 hr to 01.00
      hr. AUC analysis showed significant differences between sitting and lying
      positions (t=2.84; P<0.05; df=5), with higher melatonin levels associated with
      the sitting position (mean difference in peak concentration of 17.1 pg/ml).
      Furthermore a change in posture from the lying to the standing position produced
      a statistically significant increase in melatonin concentrations (final stage)
      (t=-3.37; P<0.05; df=5) (mean difference in peak concentration of 28.5 pg/ml). No
      differences were found with a change in posture from a sitting to a standing
      position. The hemoconcentration and hemodilution associated with posture changes
      may play a role in altering plasma protein bound hormones such as melatonin.

PMID- 9572532
TI  - Estrogen modulates the nocturnal synthesis of melatonin in peripubertal female
      rats.
AB  - Our objective was to evaluate the effects of estrogen deficit and of estrogen
      stimulation on the synthesis of pineal melatonin in female rats during the
      peripubertal period. The levels of melatonin and N-acetylserotonin (NAS) and the
      activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase
      (HIOMT) were determined in homogenates of pineal glands obtained from
      peripubertal female Sprague-Dawley rats 4 to 12 weeks of age in the mid-dark
      during the daily light/dark cycle. Animals were ovariectomized at 4 weeks of age;
      daily administration of estradiol benzoate (E2B, 1.0 microg/d, s.c.) was
      initiated at 4 weeks of age. A peak in the pineal levels of melatonin and NAS and
      in NAT activity was observed in untreated (control) rats with intact ovaries at 6
      weeks. HIOMT activity increased from Week 4 to 6 and remained unchanged
      thereafter. Ovariectomy at Week 4 led to significant increases in the levels of
      melatonin and of NAS and NAT in activity at Week 8. NAT activity Week 10
      resembled that of control animals, but levels of melatonin and NAS were slightly
      elevated. Ovariectomy did not affect HIOMT activity. Subcutaneous injection of
      E2B significantly decreased the levels of melatonin and NAS and of NAT activity
      at Week 4, as compared with those in control rats. E2B suppressed the ovariectomy
      induced elevation of levels of melatonin and NAS and of NAT activity, similar to
      the effect in control animals. E2B did not affect HIOMT activity. Our results
      suggest that estrogen modulates the nocturnal synthesis of melatonin in the
      pineal gland in peripubertal female rats. The effects of estrogen on melatonin
      synthesis appeared to be mediated by the modulation of NAT activity.

PMID- 9572533
TI  - Prediction of nocturnal plasma melatonin from morning urinary measures.
AB  - A growing literature indicates that blood levels of the hormone melatonin may
      have important implications for human health and well-being. Melatonin is
      synthesized and released into the general circulation at night, however, and it
      is seldom feasible to draw blood samples at night in epidemiological studies.
      There is some evidence that levels of urinary melatonin and of 6
      sulfatoxymelatonin (aMT6s), the major metabolite of melatonin, accurately reflect
      nocturnal plasma melatonin. If this is the case, urinary assays could be powerful
      tools for epidemiological studies. A laboratory-based study was performed to
      examine the relationships between nocturnal plasma melatonin, morning urinary
      melatonin, and morning urinary aMT6s levels in 78 men. The relationship between
      total nocturnal plasma melatonin and both urinary aMT6s corrected for creatinine
      and urinary melatonin is significant. Combining the two urinary measures accounts
      for 72% of the variance in total plasma melatonin. Peak nocturnal plasma
      melatonin also was significantly related to urinary melatonin and to aMT6s. The
      urinary measures show good sensitivity and specificity in identifying individual
      differences in nocturnal plasma melatonin levels. These results support the
      inclusion of morning urine samples to assess the contribution of the hormone
      melatonin in occupational or residential studies involving healthy, young men.

PMID- 9572534
TI  - The efficacy of vitamin E and melatonin as antioxidants against lipid
      peroxidation in rat retinal homogenates.
AB  - Free radical-induced oxidation can cause severe cell damage in biological
      systems. Melatonin, a pineal secretory product, is a recently identified
      antioxidant that protects cells from the damaging effects of free radicals. We
      compared the effect of melatonin and vitamin E, another antioxidant, against
      lipid peroxidation (LPO) in rat retinal homogenates. The aim was to characterize
      the antioxidative efficacy of melatonin in retina, a tissue highly susceptible to
      oxidative damage. The LPO product, malondialdehyde (MDA), was determined to
      provide an index of cell damage in vitro. After the incubation with iron(II)
      ions, the free radical scavenging effectiveness of four different concentrations
      (i.e., 0.5, 1.0, 2.0, and 4.0 mM) of vitamin E and melatonin were determined by
      comparing the final levels of MDA. Lipid peroxidation product levels were
      significantly reduced in a dose-response manner by all concentrations of vitamin
      E. Melatonin, in concentrations of either 2.0 or 4.0 mM, also significantly
      reduced LPO. Statistical analysis of the data showed that vitamin E treatment
      always yielded a lower level of LPO products than did the same concentration of
      melatonin. The concentrations of each agent required to inhibit 50% of the lipid
      damage (IC50) were 0.69 mM and 4.98 mM for vitamin E and melatonin, respectively.
      Both vitamin E and melatonin protect the retina against LPO in a dose-dependent
      manner. Although the IC50 value for melatonin is about 7.2 times higher than that
      of vitamin E, melatonin's pharmacological and physiological role in the treatment
      and/or prevention of certain retinal diseases in vivo should be further
      investigated.

PMID- 9572535
TI  - Lactoferrin suppresses loss of corneal epithelial integrity in a rabbit short
      term dry eye model.
AB  - Human tear fluid contains lactoferrin at the highest concentration. In patients
      with dry eye such as Sjogren's syndrome, the concentration of lactoferrin in the
      tears is approximately half the normal value. The present study utilizes a short
      term rabbit dry eye model to evaluate if lactoferrin containing eye drops can
      reverse any of the damage produced by blockage of blinking with an ocular
      speculum. Damage was evaluated based on the extent of methylene blue staining in
      histological sections. After 3 h of desiccation, the amount of extractable dye
      recovered following sacrifice increased by more than 4-fold in the vehicle
      treated eyes. However, in those rabbits treated with 1% lactoferrin, dye recovery
      was only 40% of the value in the vehicle-treated eyes. Between 1-3 h and over a
      concentration range from 0.01 to 1% lactoferrin, the decreases in staining were
      both time and concentration dependent. Alternatively, if 1% lactoferrin was
      applied during the desiccation period, there was partial restoration of corneal
      epithelial integrity. These results suggest that lactoferrin may be of
      therapeutic value in decreasing the loss of corneal epithelial integrity in dry
      eye.

PMID- 9572536
TI  - Aminocaproic acid and tranexamic acid increase the rate of acute corneal
      reepithelialization in Sprague Dawley rats.
AB  - Antifibrinolytic agents, epsilon-aminocaproic acid (EACA) and tranexamic acid
      (TXA), have been reported to be efficacious in the treatment of chronic
      persistent epithelial defects. Within the regulatory mechanism of corneal
      reepithelialization, fibronectin serves as a primary adhesive component in the
      healing process and anchors regenerating epithelial cells to underlying stroma.
      EACA and TXA inhibit the activation of plasmin thereby decreasing plasmin-induced
      catabolism of fibronectin. In this study, acute reepithelialization following
      treatment with EACA and TXA was evaluated in the cultured rat cornea model.
      Sprague Dawley rat corneal explants with 3 mm corneal defects, induced with 1 N
      NaOH, were cultured with either EACA or TXA. After 12 or 24 hr incubation
      periods, corneal explants were stained with bromodeoxyuridine stain for measuring
      cellular division and migration or Trypan Blue for measuring the extent of dead
      cells. Both EACA and TXA increased the rate of reepithelialization in comparison
      to an untreated control. EACA was up to 35% more efficacious than TXA. Thus, this
      study demonstrated an acute effect for EACA and TXA versus the previously
      reported efficacy of chronic therapy required for persistent epithelial defects.
      Broad applications may prove beneficial in the clinical treatment of corneal
      abrasions, persistent corneal epithelial defects, or alkali burns.

PMID- 9572537
TI  - Effects of prostaglandin E2, F2alpha, and latanoprost acid on isolated ocular
      blood vessels in vitro.
AB  - The vascular effects of PGE2, PGF2alpha and latanoprost acid on isolated bovine
      long posterior ciliary arteries and episcleral veins have been investigated using
      a small vessel myograph. PGE2 caused vasorelaxation both in the ciliary artery
      and episcleral vein (EC50: 7.9x10(-9) M and 2.1x10(-8) M respectively). Blockade
      of thromboxane receptors with GR 32191B, a TP receptor antagonist, shifted the
      concentration-response curves to the left in both preparations, probably
      indicating a slight co-stimulation of TP receptors in these vessels. Blockade of
      tachykinin NK-1 receptors had no effect on the PGE2 concentration-response curve.
      PGF2alpha caused a concentration dependent contraction in half of the ciliary
      arteries examined and relaxation in the other half. In the presence of the
      thromboxane receptor antagonist (GR 3211B) PGF2alpha always induced relaxation of
      the ciliary artery (EC50:1.3x10[-5] M). At higher concentrations PGF2alpha tended
      to slightly constrict the episcleral veins, but in the presence of the TP
      receptor antagonist (GR 32191B) only relaxation was observed. Latanoprost acid
      contracted the ciliary artery at concentrations above 10(-6) M. This effect was
      completely abolished by the TP receptor antagonist (GR 32191B). In the episcleral
      vein latanoprost acid induced a slight relaxation but in the presence of the TP
      receptor antagonist (GR 32191B) no effect was observed. These results indicate
      that PGE2 invariably induces vasorelaxation of bovine ciliary arteries and
      episcleral veins, whereas both PGF2alpha and latanoprost acid at high
      concentrations can cause vasoconstriction probably by stimulating TP receptors.
      PGF2alpha causes marked relaxation of both ciliary arteries and episcleral veins
      in the presence of the TP blocker which seems unlikely to be mediated by FP
      receptors.

PMID- 9572538
TI  - The safety and efficacy of switching timolol maleate 0.5% solution to timolol
      hemihydrate 0.5% solution given twice daily.
AB  - This study was undertaken to evaluate the safety and efficacy of switching
      patients treated with timolol maleate to timolol hemihydrate. In patients with
      ocular hypertension or chronic open-angle glaucoma treated with beta-blockers for
      at least three months, we prescribed timolol maleate solution 0.5% given twice
      daily for one month. We then switched each patient to timolol hemihydrate
      solution 0.5% (Betimol, Ciba Vision Ophthalmics) given twice daily for three
      months. This study found over the first three months in 30 completed subjects,
      using a worse eye analysis, that the intraocular pressure changed from 18.3+/-2.1
      mm Hg on timolol maleate to 18.8+/-2.3 mm Hg on timolol hemihydrate (P=0.10) 12
      hours after dosing. There was no difference in the overall incidence of
      unsolicited anterior segment side effects between timolol maleate (4 cases)
      versus timolol hemihydrate (3 cases) (P=0.69). One patient exited the study
      because of pain and burning in both eyes while on timolol maleate. No patient was
      discontinued due to loss of intraocular pressure control after switching to
      timolol hemihydrate. It was concluded that switching from timolol maleate to
      timolol hemihydrate is safe and effective in maintaining control of the
      intraocular pressure.

PMID- 9572539
TI  - A multicenter comparison of the ocular efficacy and safety of diclofenac 0.1%
      solution with that of ketorolac 0.5% solution in patients with acute seasonal
      allergic conjunctivitis.
AB  - Only one of several available ophthalmic nonsteroidal anti-inflammatory drugs
      (NSAIDs) is currently FDA approved for use in acute seasonal allergic
      conjunctivitis (SAC). Sixty patients with SAC and moderate itching and bulbar
      conjunctival injection were enrolled in a multicenter, randomized, double-masked,
      parallel-group trial comparing diclofenac sodium (DS) with ketorolac tromethamine
      (KT). Patients instilled 1 drop four times daily while awake for 14 days. Ocular
      signs and symptoms were evaluated at one and two weeks. The primary efficacy
      variables were itching and bulbar conjunctival injection. For both treatments,
      the ocular allergy sign and symptom scores were comparable at baseline. Both
      treatments evaluated in this study were well tolerated. Significant clinical and
      statistical reductions from baseline were observed in the primary efficacy
      variables. Treatment group differences were observed for the pain/soreness score
      with an advantage observed for the DS group at 30 minutes and at day 7. Our
      conclusion is that diclofenac sodium and ketorolac tromethamine acted similarly
      to reduce the ocular signs and symptoms associated with acute seasonal allergic
      conjunctivitis. There was a statistically significant advantage for the DS group
      to be free of symptoms at the day 7 visit as compared to the KT group (20.7% vs.
      3.2%).

PMID- 9572541
TI  - Failure to detect systemic levels, and effects of loteprednol etabonate and its
      metabolite, PJ-91, following chronic ocular administration.
AB  - The objective of this study was to determine the systemic exposure to loteprednol
      etabonate (LE) following its chronic, ocular instillation. This was a randomized,
      double-masked, placebo controlled, single center trial in 14 normal volunteers.
      Subjects were randomly assigned to receive either LE (n=10) or placebo (n=4) and
      instructed to instill one drop into each eye 8 times daily on Days 0 and 1 and
      four times daily on Days 2 through 42. Blood levels of loteprednol etabonate (LE)
      and its major metabolite PJ-91 (delta1 cortienic acid etabonate) in plasma, and
      circulating plasma cortisol levels were measured during the study. Plasma levels
      of LE or PJ-91 were below the level of quantitation (1 ng/mL) for all subjects in
      both treatment groups. Plasma cortisol levels were all within the normal range.
      Chronic exposure to LE at a concentration and frequency equal to or greater than
      the intended therapeutic dose does not result in detectable systemic levels or
      hypothalamic pituitary axis suppression.

PMID- 9572540
TI  - Intravitreal and plasma cidofovir concentrations after intravitreal and
      intravenous administration in AIDS patients with cytomegalovirus retinitis.
AB  - This study was undertaken to evaluate the intravitreal and plasma concentrations
      of cidofovir (HPMPC) after intravitreal and intravenous administration in AIDS
      patients with cytomegalovirus retinitis. Cohort series; undiluted vitreous and
      blood were collected from 9 patients at the time of pars plana vitrectomy.
      Vitreous samples from 9 eyes of 9 patients and plasma samples from 4 patients
      were assayed with high-performance liquid chromatography to determine cidofovir
      levels. The only eye that had a detectable vitreous concentration (673.7 ng/ml)
      was injected with 20 microg 24 hours prior to the surgery. The remaining samples
      including plasma were below the detection point of the assay (100 ng/ml) and were
      injected between 5 and 40 days prior to sampling. The intravitreal concentration
      of cidofovir in humans is consistent with pharmacokinetics data in laboratory
      animals, and suggests that the long duration of antiviral effect (1-3 months) in
      clinical trials is due to a prolonged intracellular half-life in retinal tissue.

PMID- 9572542
TI  - Distribution of verapamil and norverapamil in the eye and systemic circulation
      after topical administration of verapamil in rabbits.
AB  - Our purpose was to determine the pharmacokinetics of verapamil and its active
      metabolite norverapamil after topical administration of verapamil in rabbits. New
      Zealand white albino rabbits were given 50 microl of verapamil ophthalmic
      formulation topically in each eye. Samples obtained at various time points were
      analyzed with high performance liquid chromatography and tandem mass
      spectrometry. The elimination half-life of verapamil after treatment with 0.5%
      verapamil was 0.76 hour for aqueous, 4.34 hours for vitreous, and 1.82 hours for
      serum. The peak concentrations for aqueous, vitreous, and serum were 2.34 x 10(
      6) M by 0.5 hour, 1.57 x 10(-7) M at 2 hours, and 3.39 x 10(-8) M by 0.5 hour
      following instillation of one drop of 0.5% verapamil; and 1.41 x 10(-6) M by 0.5
      hour, 5.48 x 10(-8) M at 4 hours, and 1.20 x 10(-8) M by 0.5 hour following 0.25%
      verapamil, respectively. The metabolite norverapamil was found at peak
      concentrations of 8.65 x 10-(8) M by 0.5 hour in aqueous, 1.65 x 10(-8) M at 2
      hours in vitreous, and 1.30 x 10(-9) M by 0.5 hr in serum following
      administration of 0.5% verapamil. The elimination half-life of norverapamil for
      aqueous, vitreous, and serum following treatment with 0.5% verapamil was 0.91
      hour, 1.43 hours, and 3.60 hours, respectively. We conclude that topical
      verapamil, administered to the rabbit eye, is rapidly absorbed in the aqueous,
      vitreous, and blood. Norverapamil, which is an active metabolite of verapamil,
      can be detected in the aqueous and vitreous of the rabbit eye after topical
      administration, suggesting enzymatic degradation of verapamil within the eye.

PMID- 9572543
TI  - Diabetic-like corneal sensitivity loss in galactose-fed rats ameliorated with
      aldose reductase inhibitors.
AB  - This study investigated whether diabetic-like corneal sensory deficits occur in
      the galactose-fed rat model of diabetic ocular complications and if such deficits
      could be prevented using either of two structurally different aldose reductase
      (AR) inhibitors, CT-112 or AL-1576. S-D rats were randomly grouped to receive a
      diet of Purina chow with either 50% starch (n=25) or 50% D-galactose (n=65). Some
      of the galactosemic rats received either 0.25% CT-112 topically 3x daily (n=15)
      or 28 mg/kg body wt/day AL-1576 systemically (n=10). The control and untreated
      galactosemic rats in the CT-112 portion of the study received equivalent topical
      doses of the vehicle. Sensitivity measurements were made with a Cochet-Bonnet
      Aesthesiometer mounted on a micromanipulator. The filament was applied to the
      central corneal surface (mean pressure of 0.96 g/mm2) and viewed using a slit
      lamp biomicroscope. Ten consecutive stimuli were conducted on each cornea and the
      average number of blink-responses was expressed as a percent of total stimuli
      effected. Mean initial corneal sensitivities were similar in all groups. Corneal
      sensitivity in the galactosemic rat was reduced (p<0.01) at each monthly
      measurement compared to control. Animals treated with CT-112 or AL-1576 showed a
      significant increase in the mean blink-response compared to untreated galactose
      fed rats and did not differ significantly from controls towards the completion of
      the 7 month study. Animals treated with AL-1576 did not develop cataracts,
      whereas those treated topically with CT-112 and untreated galactose-fed rats
      developed bilateral nuclear cataracts within 3 weeks. This is the first study to
      demonstrate decreased corneal sensitivity in the galactose-fed rat model and its
      amelioration with AR inhibitors. Thus, aldose reductase, the first enzyme of the
      polyol pathway, may have an important role in the pathogenesis of decreased
      corneal sensitivity. The model could be useful for investigating the pathogenic
      mechanism(s) involved in reduced corneal sensitivity associated with diabetic
      keratopathy in humans.

PMID- 9572544
TI  - Effect of aldose reductase inhibitor on corneal epithelial barrier function in
      galactose-fed dogs.
AB  - The effect of concomitant administration of galactose and the aldose reductase
      inhibitor(ARI) Epalrestat (Kinedak) on corneal barrier function was examined in
      dogs. Six-month-old male beagles were rendered aphakic in one eye and then
      divided into four groups as follows: 1) a control group fed on 30% cellulose, 2)
      a galactosemic group fed on 30% galactose, 3) a 30% galactose-fed group treated
      with low dose (20 mg/kg) ARI and 4) a 30% galactose-fed group treated with high
      dose (50 mg/kg) ARI. Forty-one months after the start of these diets, corneal
      autofluorescence and the corneal barrier function were measured in each dog using
      anterior fluorophotometry (FL-500). When barrier function was analyzed in non
      operated eyes, fluorescence data were significantly higher in the galactosemic
      group compared to the control group. In non-operated eyes, fluorescent data in
      high-dose ARI treated group were significantly lower than those in the
      galactosemic group. However, in operated eyes, no significant difference was
      observed between the galactosemic group and the ARI treated groups. Similar
      trends were observed when corneal autofluorescence of each group was compared.
      Long-term galactose feeding appeared to damage corneal epithelial barrier
      function. This damage was not observed in the high-dose ARI treated group
      suggesting that this damage may be linked to the polyol pathway.

PMID- 9572545
TI  - Multiple factors including subgenomic RNAs and reduced viral protein expression
      are associated with a persistent infection by porcine rubulavirus (LPMV).
AB  - The synthesis of virus specific RNA and the expression of viral proteins in PK-15
      cells persistently infected with the porcine rubulavirus LPMV have been studied
      at two different cell-passages following establishment of persistency (passages
      25 and 65). Protein analysis of persistently infected cells and the virus
      particles released from these failed to demonstrate the presence of the
      polymerase (L) protein. A decrease in the amount of the phospho- (P) protein was
      also noted. The genome and mRNAs, both mono- and bicistronic, could readily be
      identified in the persistently infected cells with the exception of the L mRNA.
      By analysis of transcription gradients generated using the NIH Image analysis
      software, as well as analysis of the editing frequency, it was concluded that the
      changes in viral protein levels in persistently infected cells could be
      associated with a reduction in the amount of L mRNA and a shift in editing of the
      P gene. In addition, several large subgenomic RNAs of both the internally deleted
      and copy-back type were found in the persistently infected cells. The relevance
      of these findings to the persistent state is discussed.

PMID- 9572546
TI  - Bovine herpesvirus 1-induced apoptosis: phenotypic characterization of
      susceptible peripheral blood mononuclear cells.
AB  - Bovine herpesvirus 1 (BHV-1), a member of the Alphaherpesvirinae, induces
      apoptotic cell death in peripheral blood mononuclear cells (PBMC). To investigate
      the process by which BHV-1 induces apoptosis, we determined the susceptibility of
      the three main PBMC subpopulations to BHV-1-induced apoptosis. This study shows
      that BHV-1 can induce apoptosis individually in T lymphocytes, B lymphocytes and
      monocytes. This conclusion is based on the following findings: (i) BHV-1
      substantially reduces the percentages of viable T and B lymphocytes in PBMCs.
      (ii) Concomitant detection of cell phenotype and apoptosis indeed showed higher
      percentages of apoptotic T lymphocytes and B lymphocytes in BHV-1-infected PBMCs
      than in mock-infected cells. (iii) Each individual PBMC subpopulations (B
      lymphocytes, T lymphocytes and monocytes) undergo apoptosis when incubated with
      BHV-1. These data also suggest that BHV-1 does not require the recruitment of one
      or more individual PBMC subpopulations (e.g. cytotoxic cells) to induce
      apoptosis. Finally, we observed that BL-3 cells which have been characterized as
      bovine tumoral B lymphocytes also undergo apoptosis when incubated with BHV-1.
      Therefore, the use of the BL-3 cell line provides a new experimental model to
      investigate the apoptotic process induced by BHV-1 in vitro.

PMID- 9572547
TI  - Construction of a recombinant feline herpesvirus type 1 expressing Gag precursor
      protein of feline immunodeficiency virus.
AB  - We constructed a deletion mutant of feline herpesvirus type 1 (FHV-1) and a
      recombinant FHV-1. The deletion mutant is the virus with a region (367 bp)
      deleted from the start codon of thymidine kinase (TK) gene to the SmaI site
      within the TK gene, and the other is a recombinant FHV-1 expressing Gag protein
      of feline immunodeficiency virus (FIV), in which a cDNA encoding the Gag protein
      of FIV was inserted at the TK deletion site of the former deletion mutant. These
      viruses were designated as C7301ddlTK and C7301ddlTK-gag, respectively. Growth
      kinetics of these viruses in Crandell feline kidney cells was similar to that of
      the parent C7301 strain. By immunoblot analysis, C7301 ddlTK-gag was confirmed to
      express the FIV Gag precursor protein in the cells.

PMID- 9572548
TI  - Transient marker stabilisation: a general procedure to construct marker-free
      recombinant vaccinia virus.
AB  - Recombinant vaccinia viruses based on the highly attenuated Modified Vaccinia
      Ankara (MVA) strain expressing HIV-1 antigen genes were constructed by a novel
      procedure involving the transient use of two marker genes. The selectable markers
      used, the Escherichia coli guanine phosphoribosyltransferase (gpt) and the beta
      galactosidase (lacZ) genes, are not retained within the final recombinant virus.
      The transient marker stabilisation (TMS) procedure allows the generation of
      marker-free recombinant viruses in a series of simple plaque purification steps.
      HIV-1 gag pol genes were inserted into two loci of vaccinia MVA demonstrating the
      efficiency of the procedure.

PMID- 9572549
TI  - Characterization of petunia flower mottle virus (PetFMV), a new potyvirus
      infecting Petunia x hybrida.
AB  - With the introduction of cutting-grown Petunia x hybrida plants on the European
      market, a new potyvirus which showed no serological reaction with antisera
      against any other potyviruses infecting petunias was discovered. Infected leaves
      contained flexuous rod-shaped virus particles of 750-800 nm in length and
      inclusion bodies (pinwheel structures) typical for potyviruses in ultrathin leaf
      sections. The purified coat protein with a Mr of approximately 36 kDa could be
      detected in Western immunoblots with a specific antibody to the coat protein of
      the petunia-infecting virus. The 3' end of the viral genome encompassing the 3'
      non-coding region, the coat protein gene, and part of the NIb gene was amplified
      from infected leaf material by IC/PCR using degenerate and specific primers.
      Sequences of PCR-generated cDNA clones were compared to other known sequences of
      potyviruses. Maximum homology of 56% was found in the 3' non-coding region
      between the petunia isolate and other potyviruses. A maximum homology of 69% was
      found between the amino acid sequence of the coat protein of the petunia isolate
      and corresponding sequences of other potyviruses. These data indicate that the
      petunia-infecting virus is a previously undescribed potyvirus and the name
      petunia flower mottle virus (PetFMV) is suggested.

PMID- 9572550
TI  - Regulation of single-strand RNA synthesis of alfalfa mosaic virus in non
      transgenic cowpea protoplasts by the viral coat protein.
AB  - We have compared the RNA synthesis of alfalfa mosaic virus in complete (by RNAs
      1, 2 and 3) and incomplete infections (by RNAs 1 and 2) of cowpea protoplasts.
      Both viral RNA polymerase activity and accumulation of viral RNA were measured.
      By annealing RNA in solution with 32P-labelled probes of plus and minus polarity
      followed by treatment with ribonucleases, we determined viral RNAs quantitatively
      in both single- and double-stranded RNA fractions. The accumulation of single
      stranded RNA of positive polarity differed considerably between the two types of
      infection (250 ng vs. less than 1 ng per 10(5) protoplasts), although viral RNA
      polymerase activities as measured in vitro and the concentrations of minus RNA
      were similar. Since the method also measured fragmented RNA, this difference is
      probably not due to lack of protection of viral RNA by coat protein during
      incomplete infection. Synthesis of single-stranded plus RNA requires either RNA 3
      itself or one of its gene products. We postulate that coat protein is the
      stringent regulator of alfalfa mosaic virus genomic expression.

PMID- 9572551
TI  - Molecular cloning of an Australian isolate of hepatitis C virus.
AB  - The genomic sequence of an Australian isolate of hepatitis C virus (HCV) was
      determined from overlapping cDNA clones obtained from a small amount (1.2 ml) of
      serum from a single individual with hepatitis C. The isolate (HCV-A) comprises
      9379 nucleotides (nt) including 324 nt of a 5' untranslated region (5'UTR), a
      single long open reading frame of 9033 nt encoding a polyprotein of 3010 amino
      acids (aa), and 22 nt of a 3' untranslated region (3'UTR). Sequence analysis of a
      251 nt region within the 5'UTR and a 222 nt region within NS5B showed the
      genotype of HCV-A to be subtype 1b. A striking difference in the amino acid
      sequence of the hypervariable region 1 (HVR-1), and not in the surrounding
      sequence, was seen in cDNA clones synthesised from serum taken 52 weeks after the
      initial sample, indicating a significant population diversity of HCV genomes.

PMID- 9572552
TI  - Mapping the genetic determinants of human immunodeficiency virus type 2 for cell
      tropism and replication efficiency.
AB  - Two distinct infectious molecular clones of human immunodeficiency type 2 (HIV-2)
      were analyzed for their biological properties in six cell lines. Fourteen
      chimeric and ten mutant viruses were constructed from these two viral genomes to
      localize the genetic determinants responsible for the phenotypes. Growth property
      of the viruses in the cell lines, together with the biochemical data, showed that
      a major determinant for the viral tropism resides in the env gene. In addition,
      in some cell lines, the accessory genes vif and nef affected the efficiency of
      virus replication. Thus, like HIV-1, mutations in the auxiliary and env genes of
      HIV-2 contributed much to the differences in virological characteristics.

PMID- 9572553
TI  - The major late promoter and bipartite leader sequence of fowl adenovirus.
AB  - The region of the fowl adenovirus serotype 10 (FAV-10) genome containing the
      major late promoter (MLP) and leader sequences was determined and appropriate
      genomic fragments were cloned and sequenced. A TATA box was identified and the
      location of the putative transcription start site was determined. By using
      synthetic primers from the transcription start site in conjunction with
      oligonucleotides from the coding regions of the penton base and hexon genes, cDNA
      was produced from late mRNA isolated from cell cultures infected with FAV-10 at
      24 h post-infection. The resulting cDNA was cloned and sequenced and the leader
      sequences thus identified. It was found that the FAV-10 MLP utilized only two
      leader sequences (a bipartite leader). By comparison with human adenoviruses
      (HAVs) it appeared that the second leader in HAVs was absent from the FAV-10. The
      second leader sequences of FAV-10 was larger than either the second or third
      leaders of HAVs, but was 29 basepairs shorter than the combined size of the
      leader sequences 2 and 3 from HAV-2. To confirm the transcription start site and
      leader sequences, single stranded cDNA was produced from mRNA using the primers
      from within the coding sequence for the penton base or hexon. A tail of dGTP's
      was added and cDNA synthesis was completed using an oligonucleotide from within
      the hexon or penton base coding sequence and a second poly-dCTP oligonucleotide.
      Sequencing of the resultant G-tailed DNA confirmed the location of the
      transcription start site as an adenosine residue 24 basepairs upstream from the 3
      prime (3') end of the TATA box. Sequencing 5' of the TATA box failed to reveal
      any sequence similarity with the human adenovirus upstream stimulatory factor
      (USF). Various plasmids were constructed which placed the determined sequences of
      the MLP, leader, and the region upstream of the TATA box linked to the co-acetyl
      acid transferase (CAT) gene. These expression plasmids in transient expression
      assays of CAT activity in primary chicken kidney cell culture with or without FAV
      10 co-infection were determined. These experiments showed that the cassette
      containing sequences 5' of the TATA box expressed CAT to a much greater level
      than cassettes not containing this upstream region and that the presence of virus
      significantly increased the activity of the promoter following the onset of viral
      DNA replication. Without the 5' region, cassettes failed to express above
      background levels. These results suggest that the basic structure of the fowl
      adenovirus MLP is similar to that of the human adenovirus although it utilizes a
      bipartite rather than a tripartite leader sequence.

PMID- 9572554
TI  - The influence of the milieu on the rate of neutralisation of herpes simplex virus
      1.
AB  - The rate of neutralisation of herpes simplex virus 1 was increased by up to more
      than five hundred-fold when the virus suspension and antiserum were each diluted
      to one hundred-fold in water instead of phosphate buffered saline. This
      phenomenon, which was observed for two human positive sera and a rabbit purified
      polyclonal antibody, may represent an unrecognised homeostatic mechanism where
      neutralising antibody is 'dilution-fast' under physiological conditions of
      transudation or pathological conditions of inflammation.

PMID- 9572555
TI  - Nucleotide sequence analysis of the coat protein genes of two Korean isolates of
      sweet potato feathery mottle potyvirus.
AB  - The coat protein (CP) genes of the genomic RNA of two Korean isolates of sweet
      potato feathery mottle potyvirus (SPFMV), SPFMV-K1 and SPFMV-K2, were cloned and
      their complete nucleotide sequences were determined. Sequence comparisons of the
      two Korean isolates showed 97.8% amino acid identity in the CP cistron, and 79.9%
      to 99.0% identity with those of 6 other known SPFMV strains. Of 74 amino acid
      changes totally among the SPFMV strains, 39 changes were located at the N
      terminal region. Pairwise amino acid sequence comparison revealed sequence
      similarities of 48.6 to 70.2% between SPFMV and 20 other potyviruses, indicating
      SPFMV to be a quite distinct species. Multiple alignment of the CP cistrons from
      other potyviruses showed that most of the conserved amino acid residues of the
      genus Potyvirus are well preserved in the corresponding locations.

PMID- 9572556
TI  - Telomeric sequences from human herpesvirus 6 do not mediate nuclear retention of
      episomal DNA in human cells.
AB  - Telomeric repeat sequences (TRS) have been identified close to, but not at, the
      genome termini of several lymphotropic herpesviruses, including human
      herpesviruses 6 and 7 (HHV-6, HHV-7). The functional significance of these motifs
      remains uncertain. Since telomeric sequences can mediate stable retention of
      episomal DNA in yeast, we have tested whether the TRS motifs from HHV-6 might
      mediate a similar function in human cells. Several candidate sequences were
      assessed for their ability to provide nuclear retention to an autonomously
      replicating vector in rapidly dividing human tissue culture cells, including HHV
      6 TRS DNA, as well as telomeric DNA from human cells and sequences from Epstein
      Barr virus (EBV). However, only a vector carrying the EBV-derived retention
      mechanism showed a significant level of nuclear retention. Neither the HHV-6 TRS
      motifs, nor human telomeric sequences, mediated nuclear retention of episomal DNA
      in human cells.

PMID- 9572557
TI  - Lack of restriction of growth for aquareovirus in mammalian cells.
AB  - The striped bass (SBR) virus, a member of the recently described aquareoviruses,
      infected, caused cytopathic effects (CPE), and replicated in mammalian cells. The
      virus caused CPE in all 7 of the mammalian cell lines investigated. SBR virus
      functioned best at lower temperatures and it is these lower temperatures that
      appeared to be restricting factors for growth of some mammalian cells. At 22
      degrees C the SBR virus grew to similar titers in both chinook salmon embryo
      (CHSE) cells and in mammalian cells. Analysis of viral polypeptide and RNA
      synthesis suggests that the restriction for viral growth at higher temperatures
      occurs after adsorption but before transcription and translation of viral genes.
      The fact that SBR virus did not grow at 37 degrees C implies that aquareoviruses
      are unlikely to be human pathogens.

PMID- 9572558
TI  - Inhibition of foot and mouth disease virus (FMDV) uncoating by a plant-derived
      peptide isolated from Melia azedarach L leaves.
AB  - Meliacine (MA), a peptide isolated from leaves of the high plant Melia azedarach
      L inhibited the multiplication of foot and mouth disease virus (FMDV) in BHK-21
      cells. In this report, we establish that the MA-inhibitable process takes place
      within the first hour of the viral reproductive cycle. MA had no virucidal effect
      and did not affect adsorption and penetration of the virus in cells. In
      experiments with neutral red-labeled virus, it was found that MA significantly
      suppressed the development of photoresistance of the virus in infected cells. In
      untreated cultures nearly all virus which adsorbed to cells was uncoated within 1
      h at 37 degrees C, whereas in treated cultures, even after 3 h only 3% of the
      virus was uncoated. Labeling of BHK-21 cells with acridine orange showed that MA
      affects the pH of intracellular acidic vesicles. Therefore, it is concluded that
      MA prevents the process of uncoating of FMDV in BHK-21 cells by inhibiting
      vacuolar acidification.

PMID- 9572559
TI  - Herpes simplex virus type 1 ICP-0 induces reactivation of pseudorabies virus from
      latently infected trigeminal ganglia explant cultures.
AB  - Pseudorabies virus (PrV), like other alphaherpesviruses, is a neurotropic virus
      that can establish a latent infection in swine. Reactivation of PrV from latency
      may occur spontaneously or after induction with corticosteroids. The mechanisms
      involved in the establishment of latency and reactivation are currently unknown.
      Here, we examined gene-specific reactivation of PrV by herpes simplex virus type
      1 (HSV-1) immediate early protein, ICP-0. Primary neuronal cell cultures
      established from the trigeminal ganglia of latently infected swine were
      superinfected with recombinant adenoviruses expressing ICP-0. Reactivation of PrV
      occurred in cultures that were superinfected with two different ICP-0-expressing
      adenovirus recombinants, but not in cultures that were either mock-infected, or
      superinfected with wild-type adenovirus, or recombinant adenoviruses not
      expressing ICP-0. Infectious PrV was detected between 4 and 7 days postinfection,
      regardless of the promoter driving expression of ICP-0. Results from these
      experiments show that HSV-1 ICP-0, a homologue of PrV EP0, can induce PrV
      reactivation from explanted trigeminal ganglia of latently infected swine.

PMID- 9572560
TI  - Comparative sequence analysis of open reading frames 2 to 7 of the modified live
      vaccine virus and other North American isolates of the porcine reproductive and
      respiratory syndrome virus.
AB  - To elucidate changes associated with the attenuated virulence in a modified live
      porcine reproductive and respiratory syndrome (PRRS) vaccine (Boehringer
      Ingelheim Animal Health, St. Joseph, MO), derived from an American prototype ATCC
      virus VR-2332, nucleotide sequence of 3' genome covering open reading frames
      (ORFs) 2 to 7 coding regions from the vaccine virus was determined by RT-PCR with
      two overlapping fragments. Comparisons showed 98 base changes (94 substitutions,
      3 deletions, and 1 addition) out of 3318 nucleotides between the vaccine virus
      and its parental virus. There were 15, 26, 17, 29, 9, and 6 base substitutions in
      ORFs 2, 3, 4, 5, 6, and 7, respectively, resulting in 5, 13, 8, 13, 2, and 3
      amino acid (a.a.) substitutions in their deduced proteins, respectively. Most of
      these a.a. substitutions were also present in 17 known virulent/wild type PRRS
      virus isolates from North America. However, there were 1, 4, 1, and 1 unique a.a.
      substitutions in the vaccine virus ORFs 2, 3, 4, and 5 deduced proteins,
      respectively. These unique amino substitutions may be responsible for the
      attenuated virulence in the vaccine virus.

PMID- 9572562
TI  - A proposed scheme for viroid classification and nomenclature.

PMID- 9572561
TI  - Subcellular localization of the US3 protein kinase of herpes simplex virus type
      2.
AB  - One supposes that herpes simplex virus US3 gene product possessing
      serine/threonine protein kinase activity is a cytoplasmic enzyme. To determine
      its subcellular localization during viral replication we prepared an antiserum to
      a synthetic oligopeptide corresponding to the N-terminal region of the US3
      protein of HSV type 2 strain 186. The US3 protein first appeared in the cytoplasm
      of infected cell at 4 h postinfection but strong fluorescence was detected in the
      nuclei at 8 h postinfection. At 12 h postinfection fluorescence was mainly
      detected in the cytoplasm, again. Further, the US3 protein expressed alone was
      widely distributed throughout the cell, indicating that the US3 protein by itself
      can be localized in the nuclei even in the absence of any other viral proteins.
      These observations suggest that the HSV-2 US3 protein kinase may function not
      only in the cytoplasm but also in the nuclei.

PMID- 9572563
TI  - High-dose exposure to systemic phosmet insecticide modifies the
      phosphatidylinositol anchor on the prion protein: the origins of new variant
      transmissible spongiform encephalopathies?
AB  - Compulsory exposure of the UK bovine to exclusively high biannual doses of a
      'systemic' pour-on formulation of an organo-phthalimido-phosphorus warblecide,
      phosmet, during the 1980s (combined with exposure to the lipid-bound residues of
      'bioconcentrated' phosmet recycled back via the intensive feeding of meat and
      bone meal), initiated the 'new strain' modification of the CNS prion protein
      (PrP) causing the UK's bovine spongiform encephalopathy (BSE) epidemic. A
      lipophilic solution of phosmet was poured along the bovine's spinal column,
      whence it penetrated and concentrated in phospholipids of the CNS membranes,
      covalently modifying endogenous phosphorylation sites on phosphatidylinositols
      (PIs) etc., forming a 'toxic membrane bank' of abnormally modified lipids that
      'infect' any membrane proteins (such as PrP) that are programmed to conjugate
      onto them for anchorage to the membrane. Thus, phosmet invokes a primary covalent
      modification on PrP's PI anchor which, in turn, invokes an overall diverse
      disturbance upon CNS phosphoinositide second messenger feed back cycle, calcium
      homeostasis and essential free radicals; thus initiating a self-perpetuating
      cascade of abnormally phosphorylated PI-PrP that invokes a secondary
      electrostatic and allosteric disturbance on the main body of PrP impairing
      tertiary folding. Chaperone stress proteins conjugate onto misfolded PrP blocking
      its sites of proteolytic cleavage. Fresh epidemiological evidence is presented
      and experimental evidence referenced that adds support to a multifactorial
      hypothesis which proposes that BSE is a hitherto unrecognized and previously
      unmanifested class of subtle chronic phosmet-induced delayed neuro-excitotoxicity
      in the susceptible bovine.

PMID- 9572564
TI  - Vascular leakage stimulates phenotype alteration in ocular cells, contributing to
      the pathology of proliferative vitreoretinopathy.
AB  - Plasma leaking from damaged retinal blood vessels can have a significant impact
      on the pathologies of the posterior segment of the eye. Inflammation in the eye
      and metabolic change resulting from diabetes mellitus causes vascular leakage
      with alteration of the phenotype of retinal pigment epithelial (RPE) cells and
      fibrocytes, resulting in changes in cell function. Phenotypically altered cells
      then significantly contribute to the pathogenesis of retinopathies by being
      incorporated into tractional membranes in the vitreous, where they secrete matrix
      molecules, such as fibronectin, and express altered cell surface antigens. We
      hypothesize that there is a direct relationship between the leaking of plasma and
      the proliferation and phenotypic change of RPE cells and fibroblasts, thus
      exacerbating the pathology of retinal disease. If the hypothesis is correct,
      control of vascular leakage becomes an important target of therapy in
      proliferative vitreoretinopathy.

PMID- 9572565
TI  - Inhibition of cancer cell proliferation by disruption of
      interdigitated/concatenated hierarchies of metabolic control/implementation
      processes: a proposal.
AB  - With a combination of inhibitors at less than their individual 'therapeutic'
      concentrations directed against dissimilar cellular hierarchical developmental
      controls and 'downstream' metabolic pathways, it may be possible to modulate the
      biologic behavior of malignantly transformed cells synergistically. Ideally the
      cumulative systemic toxicity of such a 'polytherapy' would be reduced.

PMID- 9572566
TI  - Can snoring induce or worsen obstructive sleep apnea?
AB  - Snoring and sleep apneas are breathing disorders intimately associated during
      sleep. Most snorers are 'simple' or 'nonapneic', as the prevalence of snoring is
      much higher than that of sleep apneas. The vibrations transmitted to the
      pharyngeal structures by snoring span a large range of frequencies, while the
      energy transmitted may reach high values. A deleterious effect of these
      vibrations can therefore be considered. In 1983 a group of investigators from
      Bologna described five cases of heavy snorers of increasing severity, suggesting
      that they correspond to the natural history of 'heavy snorers' disease'. The
      present article reviews the data published since 1983 in favor of this
      hypothesis: anatomic lesions of the upper airway mucosa, pharyngeal muscles and
      nerves, and clinical observations in snorers. The conclusion stresses the absence
      of ultimate proof in favor of this attractive hypothesis: we lack the
      demonstration of a significant increase of the incidence of sleep apnea in a
      group of nonapneic snorers in a longitudinal follow-up study.

PMID- 9572567
TI  - Fatty acid acylation of dopamine in the carotid body.
AB  - In this article, we put forward a hypothesis concerning the assembling and
      storage of dopamine molecules in the dense-core vesicles of the carotid body
      chemoreceptor cell. We posit that dopamine molecules are packed and sustained in
      the vesicular form due to the formation of N-acyldopamine, a condensation product
      of fatty acid acyl chain and dopamine at the amino group of the latter. N
      acyldopamine would then be stored in a micelle-like supramolecular structure
      formed due to self-association through the hydrophilic dopamine headgroups. This
      hypothesis may help explain the perennial problem of the role of dopamine in
      chemoception. It also draws attention to the possibility of the existence of
      neurotransmitters in the N-acylated form. This could lead to the design of
      acylated compounds that would play a role of prodrugs slow-releasing active
      substances by hydrolysis into the desired environment.

PMID- 9572568
TI  - Biological strategies expressed by different Streptococcus pyogenes strains: an
      explanation of the epidemiology.
AB  - The numerous reports in the last ten years on the serious diseases caused by
      Streptococcus pyogenes indicate the continued significance of this pathogen.
      Furthermore, clinical studies and modern techniques have yielded new information
      on S. pyogenes and its pathogenic mechanisms. Although much still remains to be
      discovered about the biology of S. pyogenes, two different strategies--the
      'epidemic' and the 'endemic' strategy--can be seen in the interaction of
      different S. pyogenes strains with the human host. The challenges posed by these
      two groups of bacteria are also outlined.

PMID- 9572569
TI  - Essential fatty acids and sleep: mini-review and hypothesis.
AB  - The neurochemical basis of sleep mechanisms (onset and maintenance) is still
      controversial although the phenomenon itself is known to be mediated by more than
      a single molecule. The list of suggested endogenous sleep substances is rather
      long, and there is no single 'sleep center' identified in the brain. The role of
      fatty acids, and essential fatty acids in particular, has been ignored in sleep
      research. This review proposes an integration of the current knowledge about the
      effects of fatty acids in sleep neurochemistry, wherein fatty acids are seen to
      exert a direct effect on neuronal membrane structure or indirectly on the
      dynamics of biochemical compounds (complex lipids, prostaglandins,
      neurotransmitters, amino acids, interleukins) necessary for the initiation and
      maintenance of sleep.

PMID- 9572570
TI  - Removing the antidromically driven sensory component from cervically evoked motor
      potentials.
AB  - The purpose of this paper is to present a model for removing antidromically
      activated afferent input from cervically elicited neurogenic motor evoked
      potentials (nMEPs). nMEPs have recently been used clinically, purportedly for
      monitoring spinal cord motor function, during spine surgery. However, the nMEP
      response may be due, in part or in whole, to neural signals travelling through
      sensory rather than motor pathways. This complicates nMEP interpretation and may
      lead to false conclusions about the status of motor tracts and postoperative
      motor function. Moreover, transcranial stimulation techniques may also contain
      similar afferent contamination. Here I suggest a protocol for intraoperative use
      that should effectively remove such afferent contamination via an afferent action
      potential collision technique.

PMID- 9572572
TI  - Speech phones are a replication code.
AB  - Our ability to map sound into pronunciation--vocal imitation--is necessary for
      vocabulary learning, and so the existence of language. It is also unexplained.
      Here I show that speech is imitable due because of the brain's use of the innate
      sensitivities of the vertebrate auditory system for speech motor targets. Their
      public nature enables speech to transmit articulation information. These units I
      suggest closely link with phones, the minimal unit of speech segmentation. The
      conjecture that phones function as a replicative code removes five unexplained
      anomalies in language science: (i) why nearly eight hundred phones exist but any
      language uses only a tiny subset of them (evolutionarily this makes no sense);
      (ii) why newborn infants hear phones of all languages; (iii) why animals also
      hear them; (iv) why the Wernicke's and Broca's areas arose from homologous areas
      in primates which process imitation, and why (v) in humans these areas process
      nonspeech imitation.

PMID- 9572571
TI  - A central role for protein kinase C overactivity in diabetic glomerulosclerosis:
      implications for prevention with antioxidants, fish oil, and ACE inhibitors.
AB  - The primary etiologic factor in diabetic glomerulosclerosis appears to be an
      overproduction of transforming growth factor-beta by mesangial cells, which in
      turn reflects a hyperglycemically mediated overactivation of protein kinase C
      (PKC) throughout the glomerulus. Membrane-active antioxidants, fish oil, and
      angiotensin-converting enzyme inhibitors can act to down-regulate glomerular PKC
      activity, via a variety of mechanisms that may include activation of
      diacylglycerol kinase and suppression of phosphatidate phosphohydrolase, support
      of endothelial nitric oxide and heparan sulfate production, inhibition of
      thromboxane and angiotensin synthesis/activity, and correction of glomerular
      hypertension. The beneficial impact of these measures on vascular endothelial
      function may be of more general utility in the prevention of diabetic
      complications such as retinopathy, neuropathy, and atherosclerosis. Adjunctive
      use of gamma-linolenic acid is indicated for prevention of neuropathy, and it is
      conceivable that bioactive chromium will have protective activity not solely
      attributable to improved glycemic control. Re-establishing euglycemia must
      clearly remain the core strategy for preventing diabetic complications, but when
      glycemic control remains suboptimal, practical, safe measures are at hand for
      decreasing risk.

PMID- 9572573
TI  - Tumor microcirculation and its significance in therapy: possible role of omega-3
      fatty acids as rheological modifiers.
AB  - Despite the great efforts to find new drugs or devices to suppress cancer cells,
      attempts to modify microcirculation and therefore the state of tumor cells and
      their surrounding normal tissues have not been given the attention they deserve.
      Solid tumors are composed of highly heterogeneous populations of malignant,
      stromal and inflammatory cells in a continuously adapting extracellular matrix.
      All of the above components interact and regulate each other to produce distinct
      microenvironments within the tumor mass. Abnormal microcirculation plays a
      particular role in the maintenance of this anomalous condition and favors the
      formation of metastasis, but on the other hand provides the therapist with an
      important site for intervention. In this brief overview we attempt to outline
      three aspects: (a) how the anomalous tumor blood flow provokes the nonuniform
      distribution of oxygen and nutrients within the tumor mass, thus determining
      different responses to the various cancer therapies; (b) how hemorheology is the
      clinical parameter most easily modified and (c) how omega-3 essential fatty acids
      are natural drugs that could be used in this sense beyond their antitumoral
      properties.

PMID- 9572574
TI  - Mild hypothermia protects rat hippocampal CA1 neurons from irreversible membrane
      dysfunction induced by experimental ischemia.
AB  - In order to examine the effects of hypothermia on the changes in membrane
      potential induced by experimental ischemia (deprivation of oxygen and glucose),
      intracellular recordings were made from single CA1 pyramidal neurons in slice
      preparations of rat hippocampus. Application of ischemic medium caused
      irreversible changes in membrane potential consisting of an initial
      hyperpolarization, then a slow depolarization and a rapid depolarization. At
      temperatures of 35 degrees C and 37 degrees C, once the rapid depolarization
      occurred, readministration of oxygen and glucose failed to restore the membrane
      potential, a state referred to as irreversible membrane dysfunction. When the
      temperature was lowered to between 27 degrees C and 33 degrees C, the membrane
      potential returned to the control resting membrane potential in 75% of the
      neurons. The temperature coefficients (Q10) of the latency, the amplitude, and
      the maximal slope of the rapid depolarization were 2.5, 1.4 and 2.9,
      respectively. It is concluded that the critical neuroprotective temperature in
      ischemia-induced membrane dysfunction is found to be 33 degrees C in single CA1
      neurons in vitro.

PMID- 9572575
TI  - Nitric oxide contributes to irreversible membrane dysfunction caused by
      experimental ischemia in rat hippocampal CA1 neurons.
AB  - The effects of agents which affect the action of nitric oxide (NO) were studied
      intracellularly on the ischemia-induced changes in membrane potential of single
      CA1 pyramidal neurons of the rat hippocampal slice preparations. The N-methyl-D
      aspartate (NMDA) receptor antagonists, (+/-)-2-amino-5-phosphonopentanoic acid
      (AP5, 250 microM) or Co2 (2 mM) restored the membrane potential in more than 80%
      of the neurons. In about 60% of the neurons, the membrane potential was partially
      recovered as a result of exposure to the NO synthase inhibitor, NG-nitro-L
      arginine (100 microM). The NO scavengers, carboxy-2-phenyl-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO, 300 microM) and hemoglobin
      (10 microM) restored the membrane potential in all neurons examined. Superoxide
      dismutase (50 U/ml) protected about 75% of the neurons from irreversible membrane
      dysfunction. It is concluded that the release of NO induced by experimental
      ischemia may result in the irreversible membrane dysfunction, and that a NO
      scavenger, carboxy-PTIO, prevents the ischemic changes in membrane potential.
      With respect to ischemic brain damage, the neuroprotection provided by carboxy
      PTIO may have clinical relevance in the management of a variety of neurological
      conditions.

PMID- 9572577
TI  - Brain potentials reveal the timing of face identity and expression judgments.
AB  - Event-related brain potentials (ERPs) were recorded from multiple scalp locations
      from young human subjects while they performed two different face processing
      tasks. The first task entailed the presentation of pairs of faces in which the
      second face was either a different view of the first face or a different view of
      a different face. The subjects had to decide whether or not the two faces
      depicted the same person. In the second task, pairs of faces (frontal views) were
      presented with the task of judging whether the expression of the second face
      matched that of the face. Incongruous faces in the view (identity) matching task
      gave rise to a negativity peaking at about 350 ms with a frontocentral maximum.
      This effect was similar to the N400 obtained in linguistic tasks. ERP effects in
      the expression matching task were much later and had a different distribution.
      This pattern of results corresponds well with neuropsychological and neuroimaging
      data suggesting specialized neuronal populations subserving identity and
      expression analysis but adds a temporal dimension to previous investigations.

PMID- 9572576
TI  - Modulation of chromatic difference in receptive field size of H1 horizontal cells
      in carp retina: dopamine- and APB-sensitive mechanisms.
AB  - Chromatic aspects of receptive field size in the H1 horizontal cell syncytium of
      the carp retina were investigated using spectral photostimuli (blue or red)
      presented in the form of either a pair of a small spot and annulus, or a narrow
      moving slit. In the light-adapted retina, the receptive field for the blue
      stimulus was found to be significantly smaller than that for the red, i.e. there
      was a chromatic difference in the receptive field size. During the course of dark
      adaptation, the overall receptive field size increased, but the chromatic
      difference decreased. Immediately after adaptation to bright light, the receptive
      field sizes were reduced significantly, but the chromatic difference increased,
      mainly due to a greater reduction in the receptive field for the blue stimulus.
      Application of dopamine (5 microM) to a dark-adapted retina gradually decreased
      the receptive field size for both colours, but the chromatic difference became
      larger, again due to a greater reduction in the receptive field size for the blue
      stimulus. 2-Amino-4-phosphonobutyrate (APB) applied to light-adapted retinae at a
      working concentration of 1 mM, greatly expanded the receptive field size and
      suppressed the chromatic difference due to the effect being greater for the
      receptive field for the blue stimulus. The effect of APB was slow and cumulative.
      On the other hand, intracellular injection of cGMP or dibutyryl-cGMP increased
      the chromatic difference in the receptive field size. It is suggested (i) that
      the chromatic difference in the receptive field size could be due to a cGMP
      coupled, conductance-decreasing receptor mechanism activated by APB; and (ii)
      that the mechanism is associated with short-wavelength sensitive cone input to
      the H1 cells and operates in the light-adapted state of the retina.

PMID- 9572578
TI  - Different effect of oxytocin on membrane potential of supraoptic oxytocin neurons
      in virgin female and male rats in vitro.
AB  - The effects of oxytocin on membrane potential were investigated in the supraoptic
      nucleus (SON) neurons of rats using whole-cell patch-clamp technique. SON neurons
      were electrophysiologically identified as oxytocin (OT) or vasopressin (VP)
      neurons. Application of OT (1 x 10[-7] M) hyperpolarized membrane potentials of
      OT neurons in virgin female rats but depolarized membrane potentials of putative
      OT neurons in male rats. The membrane conductance of SON neurons were increased
      by treatment of OT in both sexes, suggesting that OT increased the opening of
      channels on SON neurons. The reversal potential of OT neurons in virgin female
      rats and putative OT neurons in male rats under OT effective conditions were -66
      +/- 1 mV (n = 4) and -46 +/- 2 mV (n = 5), respectively. These data suggest that
      OT released within the SON suppresses the activity of OT neurons in virgin female
      rats while it excites putative OT neurons in male rats.

PMID- 9572579
TI  - Dopamine metabolism in the striatum of hemiparkinsonian model rats with
      dopaminergic grafts.
AB  - To investigate dopamine (DA) levels as well as DA metabolism by which the
      striatal DAergic grafts may bring the functional recovery to hemiparkinsonian
      model rats, a microdialysis study was performed in the striatum, and an
      autoradiographic analysis for DA transporter was made. In hemiparkinsonian model
      rats, the concentrations of DA, dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) in striatal perfusates, decreased considerably (less than
      5%, of control levels). In grafted rats that showed motor recovery, the
      concentration of DA recovered to almost control level, and DOPAC and HVA to about
      20% of controls' suggesting that the rate of DA metabolism is low. L-DOPA loading
      to grafted rats induced a big release of DOPAC and HVA, thus the DOPAC/DA ratio
      was close to that of the controls'. Methamphetamine loading increased the
      concentration of DA but did not change the level of DOPAC and HVA. Haloperidol
      loading increased DA, DOPAC and HVA. [3H]mazindol binding that reflects the
      activity of the DA transporter decreased considerably in hemiparkinsonian model
      rats, but it reappeared more or less in grafted rats. Data indicated that in
      grafted striatum, the extracellular DA level is almost normal level while the
      rate of DA metabolism is low. By L-DOPA loading, the grafts show the capacity to
      synthesize, release and metabolize DA and then the DOPAC/DA ratio is normalized.
      Responses to methamphetamine and haloperidol, as well as the results of the
      autoradiographic study suggest that the grafts are under a good feedback
      regulation of DA metabolism.

PMID- 9572580
TI  - Expression of basigin, a member of the immunoglobulin superfamily, in the mouse
      central nervous system.
AB  - Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin
      superfamily. Chicken Bsg (HT7/neurothelin/ 5A11) is expressed in neuroblasts, but
      disappears from neurons after a specific stage of cytodifferentiation, and
      becomes restrictedly expressed in the capillary endothelium in the adult brain.
      We show herein by means of in situ hybridization that Bsg mRNA was expressed in
      neuroblasts in 13.5 day old mouse embryos. In the adult mouse, Bsg was
      differentially expressed in subregions of the brain. Strong Bsg expression was
      detected in the limbic system, including the olfactory system, hippocampal
      formation, septal area, amygdala, thalamic anterior nuclei, hypothalamus,
      mesencephalic tegmentum, entorhinal cortex, and cingulate gyrus. Bsg was also
      intensely expressed in the retinal neuronal layers, the Vth layer of the cerebral
      neocortex, Purkinje cells of the cerebellum, several nuclei of the brain stem,
      and the gray matter of the spinal cord. Although in situ hybridization showed a
      weak signal in the brain capillary endothelium, protein expression of Bsg was
      strong enough to be detected by immunohistochemistry. Northern blot analysis
      confirmed the strong expression of Bsg in the central nervous system. Taking into
      account that Bsg knockout mice exhibit abnormalities in behavior, but a normal
      blood-brain barrier function, the present findings suggest that Bsg functions
      actively in neuronal interactions in the central nervous system.

PMID- 9572581
TI  - Distribution of a metabotropic glutamate receptor, mGluR2, in the central nervous
      system of the rat and mouse: an immunohistochemical study with a monoclonal
      antibody.
AB  - The distribution of a metabotropic glutamate receptor mGluR2 in the central
      nervous system was immunohistochemically examined in the rat and mouse with a
      monoclonal antibody raised against an N-terminal sequence of rat mGluR2 (amino
      acid residues 87-134). Neuronal cell bodies with mGluR2-like immunoreactivity
      (mGluR2-LI) were clearly shown in the horizontal cells of Cajal in the cerebral
      cortex, neurons in the triangular septal nucleus and medial mammillary nucleus,
      Golgi cells and the unipolar brush cells in the cerebellar cortex, and Golgi-like
      and unipolar brush-like cells in the cochlear nucleus. Neuropil was intensely
      immunostained in the accessory olfactory bulb, bed nucleus of the accessory
      olfactory tract, neocortex, cingulate cortex, retrosplenial cortex, subicular and
      entorhinal cortices, stratum lacunosum-moleculare of CA1 and CA3, molecular layer
      of the dentate gyrus, periamygdaloid cortex, basolateral amygdaloid nucleus, bed
      nucleus of the anterior commissure, caudate-putamen, accumbens nucleus, thalamic
      reticular nucleus, anteroventral and paraventricular thalamic nuclei, granular
      layer of the cerebellar cortex, anterior and ventral tegmental nuclei, granular
      layer of the cochlear nucleus, and parvicellular part of the lateral reticular
      nucleus. Many axons in the white matter and fiber bundles were also
      immunostained. No glial cells with mGluR2-LI were found. No particular species
      differences were found in the distribution pattern of mGluR2-LI between the rat
      and mouse. The results indicate that mGluR2 is expressed not only in somato
      dendritic domain, but also in axonal domain of excitatory and inhibitory neurons.

PMID- 9572582
TI  - Functional magnetic resonance imaging during recognition of written words:
      Chinese characters for concrete objects versus abstract concepts.
AB  - An attempt was made to apply functional magnetic resonance imaging (fMRI) to
      reveal cortical areas activated upon presentation of two groups of Chinese
      characters in six normal right-handed, male, Japanese subjects. Presentation of
      the characters representing 'abstract concepts' activated the bilateral occipital
      region without a significant difference between the bilateral occipital and
      temporal regions. Presentation of the characters representing 'concrete objects'
      resulted in significantly stronger activation in the left occipital and temporal
      regions. These results suggest that recognition of concrete characters involves a
      stronger initial process in the left occipital temporal cortices than recognition
      of abstract characters.

PMID- 9572583
TI  - Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through
      dopamine transporter expressed in HEK293 cells.
AB  - Tetrahydropapaveroline (THP), an isoquinoline alkaloid, has been detected in
      brain and urine of Parkinsonian patients on L-dopa medication, and in the urine
      and brain of rats after L-dopa or acute ethanol administration. Since THP is
      considered to be synthesized from dopamine, it may affect dopaminergic neurons
      through the reuptake system, i.e. dopamine transporter (DAT). To determine
      whether THP has affinity for DAT, we generated a cell line which stably expresses
      DAT and examined whether THP and its derivatives could inhibit [3H]DA uptake in
      these cells. Ki of THP and three derivatives (1-benzyl-1,2,3,4
      tetrahydroisoquinoline (1BnTIQ), 1-(3',4'-dibydroxybenzyl)-1,2,3,4
      tetrahydroisoquinoline (3',4' DHBnTIQ) and 6,7-dihydroxy-1-benzyl-1,2,3,4
      tetrahydroisoquinoline (6,7 DHBnTIQ)) for inhibition of [3H]DA uptake were about
      41, 35, 23 and 93 microM, respectively, which were similar to the Ki of 1-methyl
      4-phenylpyridinium ion (MPP+) (28 microM). These results suggest that THP and its
      derivatives might be uptaken through DAT and be involved in Parkinson's disease
      and/or alcohol addiction.

PMID- 9572584
TI  - A novel method of estimating real [Ca2+]i dynamics from fluorescence signals.
AB  - To detect changes in the concentration of intracellular calcium ions ([Ca2+]i),
      fluorescence measurement techniques are used in experimental studies. When the
      calcium concentration is calculated from fluorescence signals, an equilibrium
      between calcium ions and the fluorescent dye is assumed in conventional methods.
      However, using this assumption, calculated calcium concentrations would not be an
      accurate representation of [Ca2+]i if the dynamics of [Ca2+]i are so fast that
      the reaction between calcium ions and the dye cannot reach equilibrium. In this
      report, we propose a new method of estimating [Ca2+]i in dye-free conditions from
      fluorescence signals of the dye using differential equations expressing reactions
      between calcium ions and the dye without assuming equilibrium. We compared our
      method with a conventional method with respect to calculations of [Ca2+]i using a
      model of a dendritic spine. Simulation results showed that our method gave a
      better estimation of the changes in [Ca2+]i than did the conventional method.

PMID- 9572585
TI  - Neural plasticity in the dynamics of human visual word recognition.
AB  - Repeated exposure to words leads to plastic changes in the nervous system
      throughout the lifespan, with the consequence that common words are processed
      more rapidly and accurately than rare words. Most behavior time measures
      correlate highly with the logarithm of a stimulus word's experiential frequency.
      Here, we demonstrate similar but earlier changes in the latency of a brain
      generated evoked potential recorded over the left anterior scalp as individuals
      silently read sentences. We conclude that experience can speed the processing of
      some words by at least 50 ms within the first 335 ms of visual processing.

PMID- 9572586
TI  - Genetic association studies between Alzheimer's disease and two polymorphisms in
      the low density lipoprotein receptor-related protein gene.
AB  - The E*4 allele of apolipoprotein E (APOE) is a major risk factor for Alzheimer's
      disease (AD) but the underlying mechanism is unknown. The low density lipoprotein
      receptor-related protein (LRP) is directly involved in APOE metabolism and
      therefore may alter the risk of AD associated with APOE. Two common
      polymorphisms, a tetranucleotide repeat in the 5'-region and a same-sense
      mutation in exon 3, are present in the LRP gene. Three studies have reported
      conflicting association of the tetranucleotide polymorphism with AD. The only
      study of the exon 3 polymorphism found a significant association with AD. In this
      study we examined the association of these two LRP polymorphisms with sporadic
      late-onset AD. No significant association was observed between the
      tetranucleotide polymorphism and AD. While the overall genotype and allele
      frequencies for the LRP exon 3 polymorphism were comparable between AD cases and
      controls, the frequency of the TT genotype was significantly higher in controls
      than AD (5.7% vs. 2.5%; P < 0.01). Stratification of the data by APOE genotypes
      indicated that the protective effect associated with the TT genotype was confined
      to APOE*4 carriers. Although the effect of the exon 3 polymorphism in our sample
      is small compared to the previous study, this warrants additional studies to
      confirm this putative association.

PMID- 9572587
TI  - Expression of ced-3 and ced-9 homologs in Alzheimer's disease cerebral cortex.
AB  - In order to characterize cell death mechanisms involved in Alzheimer disease
      (AD), we quantitated the expression of ced-3 and ced-9 homologs in AD frontal
      cortex. Positive (ICE, ICErel-II, ICErel-III, Ich-1L, CPP32, mch2, mch3, bcl-xS,
      bax and bak) and negative (bcl-2, bcl-xL, MCL1 and Ich-1S) regulators of
      apoptosis were successively examined using a semi-quantitative technique of
      reverse transcription-polymerase chain reaction (RT-PCR). Total RNA was extracted
      from postmortem frontal cortex of AD patients (n = 7) and controls (n = 7)
      matched for age and autolysis time. Baseline levels of message were detected for
      3 ced-3 (CPP32, Ich-1 and ICE) and 4 ced-9 homologs (bcl-x, MCL1, bcl-2 and bax)
      in the frontal cortex. There was an overexpression of the ICEalpha cDNA in AD
      patients as compared with age-matched controls (P = 0.03). Our results indicate
      that several ced-3 and ced-9 homologs are expressed in the adult human brain, and
      suggest that neuronal cell death in AD might involve an aberrant expression of
      ICEalpha.

PMID- 9572588
TI  - Induced alpha band power changes in the human EEG and attention.
AB  - Induced alpha power (in a lower, intermediate and upper band) which is deprived
      from evoked electroencephalograph (EEG) activity was analyzed in an oddball task
      in which a warning signal (WS) preceded a target or non-target. The lower band,
      reflecting phasic alertness, desynchronizes only in response to the WS and
      target. The intermediate band, reflecting expectancy, desynchronizes about 1 s
      before a target or non-target appears. Upper alpha desynchronizes only after a
      target is presented and, thus, reflects the performance of the task which was to
      count the targets. Thus, only slower alpha frequencies reflect attentional
      demands such as alertness and expectancy.

PMID- 9572589
TI  - N-methyl-D-aspartate receptors are expressed by intrinsic neurons of rat larynx
      and esophagus.
AB  - Overactivation of N-methyl-D-aspartate receptors (NMDAR), a mechanism of central
      neurotoxicity, has recently been shown to increase airway responsiveness in rat
      lungs. NMDAR have not been localized in the airways, but neurons of the myenteric
      plexus in the rat express mRNA for NMDAR. Furthermore, a population of glutamate
      containing cell bodies in the nucleus ambiguus projects to the rat larynx. On
      this basis, we hypothesized that some postganglionic parasympathetic neurons of
      the larynx, trachea and esophagus may express NMDAR. Sections of rat larynx,
      trachea and esophagus were immunocytochemically labeled for NMDAR subtype 2B
      using a specific antibody. NMDAR immunoreactivity was observed in cell bodies of
      individual neurons located in the submucosa and on the external surface of
      skeletal muscle in the larynx and also in neurons of the esophageal plexus. All
      NMDAR-positive nerve cell bodies also contained immunoreactivity for vasoactive
      intestinal peptide (VIP) and some were immunoreactive for nitric oxide synthase
      (NOS). None of the cell bodies of the tracheal plexus contained NMDAR
      immunoreactivity. The findings demonstrate that NMDAR are expressed in neurons of
      the rat larynx and esophagus and their activation may be associate with VIP or NO
      release.

PMID- 9572590
TI  - Efficient mutagenesis of zebrafish by a DNA cross-linking agent.
AB  - We developed a novel procedure for efficient mutagenesis of zebrafish using a DNA
      cross-linking agent 4,5',8-trimethylpsoralen (TMP), which is known to frequently
      induce small deletions in Escherichia coli and Caenorhabditis elegans. A specific
      locus test and pilot screenings indicated that the TMP mutagenesis procedure was
      efficient. To confirm the successful mutagenesis by TMP, we characterized mutants
      with selective impairments in the nervous system. The no tectal neuron mutation
      hindered the development of the tectal neurons, while the edawakare mutation
      resulted in the enhancement of the extension and branching of the peripheral
      axons of trigeminal ganglion and Rohon-Beard sensory neurons. These results
      suggest that the TMP mutagenesis will provide an efficient method to isolate and
      characterize zebrafish mutants at molecular level.

PMID- 9572591
TI  - Implication of alpha1-antichymotrypsin polymorphism in familial Alzheimer's
      disease.
AB  - A common polymorphism in the alpha1-antichymotrypsin (ACT) gene has been shown to
      modify the Apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD)
      risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4
      genotypes as a potential susceptibility marker for AD. Using the polymerase chain
      reaction, we analyzed the segregation of the ACT and ApoE polymorphisms in
      familial Alzheimer's disease (FAD) patients carrying mutations in Presenilin (PS)
      and APP genes and in both early onset (EO) and late onset (LO) FAD patients
      without known mutations. Our data suggest that ACT does not represent an
      additional risk factor for PS and APP mutated families. However, in LOFAD
      patients a high frequency of the combined ACT/AA and ApoE epsilon4/epsilon4
      genotypes suggest that ACT may interact with ApoE and play a role in LOFAD.

PMID- 9572592
TI  - Extensive and permanent motoneuron loss in the rat lumbar spinal cord following
      neurotoxic lesion at birth: morphological evidence.
AB  - The efficacy of the neurotoxic lectin volkensin to induce motoneuron loss in the
      lumbar spinal cord was investigated at different time-points following unilateral
      injection into the medial gastrocnemius muscle of newborn (postnatal day 1 (PD
      1)) animals, using retrograde fluorescent neuron labelling and histochemical
      procedures to evaluate the extent of the toxin-induced depletion, in comparison
      with the effects produced by neonatal crushing of the sciatic nerve. The results
      show that very low doses (2.0 ng) of volkensin intramuscularly can produce
      extensive (about 90%) and long-lasting (up to at least 8 months post-lesion)
      motoneuronal loss in the lumbar spinal cord, whose magnitude is higher than that
      observed following mechanical injury of the developing peripheral nerve (50-60%).
      Volkensin-induced motoneuronal depletion may therefore represent a useful model
      for experimental studies aimed at functional cell replacement in the immature
      spinal cord.

PMID- 9572593
TI  - Intrathecal methysergide antagonizes the antinociception, but not the
      hyperalgesia produced by microinjection of baclofen in the ventromedial medulla
      of the rat.
AB  - Microinjection of baclofen, a gamma-aminobutyric acidB (GABA[B]) receptor
      agonist, in the nucleus raphe magnus (NRM) or nucleus reticularis
      gigantocellularis pars alpha (NGCpalpha) of the rat produces antinociception at
      doses of 0.1-1.0 ng and hyperalgesia at doses of 30-150 ng in the tail-flick
      test. The antinociception is proposed to result from disinhibition of spinally
      projecting neurons in this region that contain serotonin. The hyperalgesia is
      proposed to result either from inhibition of these neurons or from disinhibition
      of a serotonergic pain facilitatory pathway that also originates in this area of
      the ventromedial medulla. To determine the involvement of bulbospinal
      serotonergic pathways in the biphasic effects of baclofen, rats were pretreated
      intrathecally with either 30 microg of methysergide or saline. Ten minutes later,
      either saline, 0.5 ng or 150 ng of baclofen was microinjected in the NRM and
      NGCpalpha, and alterations in nociceptive threshold were assessed by the tail
      flick and hot-plate tests. Intrathecal pretreatment with methysergide prevented
      the increase in tail-flick latency produced by 0.5 ng of baclofen, but did not
      prevent the decrease in tail-flick latency produced by 150 ng of baclofen.
      Neither dose of baclofen altered hot-plate latency and this lack of effect was
      unchanged by methysergide. These data support the idea that the antinociceptive
      effect of low doses of baclofen in the tail-flick test is mediated by
      disinhibition of a bulbospinal serotonergic projection and release of serotonin
      in the spinal cord. These data also suggest that the hyperalgesia produced by
      high doses of baclofen does not result from disinhibition of a serotonergic pain
      facilitatory pathway, but rather from direct inhibition of tonically-active pain
      inhibitory neurons in the NRM and NGCpalpha.

PMID- 9572594
TI  - Effects of intraseptal infusions of N-methyl-D-aspartate receptor ligands on
      memory in an object recognition task in rats.
AB  - The present study describes the effects of intraseptal microinjections of N
      methyl-D-aspartate (NMDA) or AP5, an agonist and an antagonist of the NMDA
      receptors, respectively, upon memory of rats. Animals were injected with the drug
      or vehicle immediately after the first exposure to two identical objects, and the
      duration of exploration of the familiar and a new object were evaluated 45 min or
      24 h later. Vehicle-treated rats explored the new object longer than the familiar
      object when the intertrial time was 45 min, indicating that they remembered the
      familiar object, but not when the intertrial time was 24 h. The difference of
      exploration time between the objects was increased by NMDA, but not by AP5, when
      the intertrial time was 24 h, and decreased by AP5 when the intertrial interval
      was 45 min. These results suggest that NMDA and AP5 improves and disrupts,
      respectively, the consolidation in a working memory task.

PMID- 9572596
TI  - Serum interleukin-6 and interleukin-6 soluble receptor in Alzheimer's disease.
AB  - Serum levels of interleukin-6 (IL-6) and interleukin-6 soluble receptor (IL-6sR)
      were measured in 41 patients (23 female and 18 male, mean age 72.5 years) with
      Alzheimer's disease (AD) and in 32 controls (14 women and 18 men, mean age 69.2
      years) using enzyme-linked immunosorbent assays (ELISA). Proportions of
      individuals with detectable serum IL-6 concentrations did not differ
      significantly between patients and controls. There was however, a significant
      decrease in IL-6sR levels in Alzheimer's patients when compared with controls.
      Our results suggest that there is a dysregulation of IL-6 and its soluble
      receptor in AD.

PMID- 9572595
TI  - Metabotropic glutamate receptors limit adenylyl cyclase-mediated effects in rat
      hippocampus via protein kinase C.
AB  - Glutamate receptors of the metabotropic type (mGluRs) activate protein kinase C
      in hippocampus, but few physiological functions of this pathway are known. The
      present data show that mGluRs utilize protein kinase C to inhibit another second
      messenger system, the adenylyl cyclase pathway, in neurons of the CA1 area of
      hippocampus. Activation of mGluRs prevented beta-adrenergic receptors, which
      couple to adenylyl cyclase, from blocking the slow Ca2+-dependent
      afterhyperpolarization (AHP). Since the afterhyperpolarization modulates neuronal
      responsiveness, crosstalk between protein kinase C and the adenylyl cyclase
      pathway is likely to have physiological consequences. Moreover, mGluRs themselves
      block the afterhyperpolarization, so the observed interference with the beta
      adrenergic response constitutes a hierarchical relationship in which mGluRs are
      dominant over beta-adrenergic receptors.

PMID- 9572597
TI  - Protective effects of the free radical scavengers, dimethyl sulfoxide and
      ethanol, in cerebral ischemia in gerbils.
AB  - The effects of dimethyl sulfoxide (DMSO) and ethanol, which share an ability to
      scavenge free radicals, on ischemia/reperfusion-evoked injury to hippocampal CA1
      pyramidal cells were evaluated in the Mongolian gerbil. Ischemia was induced by a
      5 min period of bilateral common carotid artery occlusion followed by reperfusion
      for 5 days. Three groups of unanesthetized gerbils were injected
      intraperitoneally with either saline, DMSO (2.8 mmol/kg) or ethanol (2.0 mmol/kg)
      30 min prior to ischemia. All three groups displayed significant increases in
      locomotor activity post-ischemia, with no differences between groups. The extent
      of CA1 pyramidal neuron loss was significantly reduced in the DMSO and ethanol
      treated gerbils. The results suggest that both agents may be useful as adjuvant
      therapies in the treatment of cerebral ischemia/reperfusion injury.

PMID- 9572598
TI  - Are the capsaicin-sensitive structures of ventral medulla involved in the
      temperature response to endotoxin in rats?
AB  - In chronic experiments on rats pretreated with bilateral microinjection of 25 nl
      1% capsaicin to the caudal ventrolateral medulla under ketamine-xylazine
      acepromazine anesthesia, an enhancement of the temperature response to
      intraperitoneal application of 3 microg/kg E. coli lipopolysaccharide as compared
      to animals who received vehicle to the caudal ventrolateral medulla was found.
      This is indicative of the involvement of the capsaicin-sensitive bulbar
      structures in thermoregulatory processes during endotoxemia.

PMID- 9572600
TI  - No implication of apolipoprotein E polymorphism in Italian schizophrenic
      patients.
AB  - Numerous studies have provided evidence for a genetic association of the
      Apolipoprotein E (ApoE) epsilon4 allele and late onset familial and sporadic
      Alzheimer's disease (AD). Clinical observations show that a proportion of
      schizophrenic patients may suffer from severe cognitive impairment. That could
      reflect a particular clinical aspect of this mental disorder or a common, yet
      unknown, neurodegenerative mechanism. We analysed the ApoE gene polymorphism in a
      sample of 69 Italian patients with schizophrenia, 140 AD patients and 121
      controls. In schizophrenic patients, the distribution of ApoE genotypes does not
      significantly differ from that of controls. No effect of the ApoE genotype on age
      of onset was found. The frequency of ApoE alleles in Italian schizophrenic
      patients is comparable with control values, suggesting that ApoE polymorphism
      does not represent a risk factor for schizophrenia.

PMID- 9572599
TI  - Role of protein kinase C in the release of [3H]acetylcholine from myenteric
      plexus treated with vesamicol.
AB  - The present experiments investigated the release of [3H]acetylcholine ([3H]ACh)
      from the guinea pig myenteric plexus treated with 2-(4
      phenylpiperidino)cyclohexanol (vesamicol), a drug that impairs ACh accumulation
      by synaptic vesicles. Ouabain, an Na+-K+ ATPase inhibitor, released [3H]ACh
      synthesised in the presence of (-)-vesamicol, while electrical field stimulation
      or KCl depolarisation were not effective to release the transmitter in this
      condition. The effect of ouabain was Ca2+-dependent and in the presence of (-)
      vesamicol it was blocked by calphostin C, an inhibitor of protein kinase C (PKC).
      In addition, stimulation of kinase C activity by a phorbol ester, but not by its
      inactive isomer, prevented (-)-vesamicol from interfering with the release of
      [3H]ACh in electrically-stimulated myenteric plexus, similar to the effect of
      ouabain. We conclude that release of [3H]ACh induced by ouabain in the presence
      of (-)-vesamicol depends on PKC activation.

PMID- 9572601
TI  - The structure of emotions during acute myocardial infarction: a model of coping.
AB  - The present state of medical care for heart attacks, or acute myocardial
      infarction (AMI), clearly indicates that rapidly and expeditiously seeking
      definitive medical care will reduce morbidity and prevent mortality. Despite the
      clearly established advantages of rapid AMI treatment, the time from the onset of
      acute symptoms of AMI to definitive medical care is often prolonged and
      individuals with a prior history of AMI and/or coronary artery disease (CAD)
      extend care-seeking. Behaviors and actions surrounding acute care-seeking are
      often fraught with complex social, psychological and emotional processes. The
      purpose of the present paper is to bring together a theoretical and an applied
      understanding of the interval of time from acute symptom onset to definitive
      medical care during AMI; and to understand the role of emotions in the care
      seeking process. This task is especially important among individuals with a prior
      history of AMI and/or CHD. These individuals can be seen as experiencing a
      "spectrum of posttraumatic disturbances", ranging from anxiety to posttraumatic
      stress disorder and alexithymia. These disturbances contribute to extended care
      seeking thereby placing the individuals at greater risk for AMI and sudden
      cardiac death. Effective intervention requires three elements. First, knowledge
      is necessary so that individual and lay others can correctly label symptoms and
      signs of an AMI. Second, it is necessary to provide feasible behaviors that
      individuals and lay others can use to access definitive medical care. Third, and
      perhaps most importantly, it is necessary to provide understanding of and skills
      to cope with the emotional arousal surrounding both the primary traumatic
      experience of symptoms and signs, potential secondary traumatic consequences of
      AMI care-seeking and tertiary trauma from the long-term consequences of CHD.

PMID- 9572602
TI  - Special not different: general practitioners' accounts of their care of dying
      people.
AB  - In modern Britain the majority of terminal care occurs in people's own homes and
      many dying people and their carers would prefer the death itself to occur in the
      home. The quality of terminal care in the home and the possibility of a home
      death depend to a great extent upon the care provided by GPs and community
      nurses. This paper reports on GPs' experiences of caring for dying people and
      their attitudes towards such work. It is based on unstructured interviews with 25
      GPs who graduated from the 1979 entry cohort to the University of Leicester
      medical school. The respondents were recruited via a questionnaire following up
      previous research with this cohort on 'fear of death'. Although self-selecting,
      interviewees were not significantly different from those who did not volunteer
      for interview in any of the statistical analyses of the questionnaire data. There
      were a number of similarities in their accounts of their care of dying people.
      Common themes were that the care of dying people was important, rewarding and
      satisfying; that the GPs saw themselves as part of a team of carers, frequently
      as team co-ordinators; good working relationships with district nurses but less
      satisfactory relationships with hospitals and social workers; that patient and
      family were both recipients of care; and honesty in communication with dying
      people, albeit tempered. Three issues of contemporary relevance were: tensions
      over the role of hospice and specialist terminal care services; care of people
      with chronic terminal illnesses other than cancer; and the role of GPs in the
      social construction of bereavement.

PMID- 9572603
TI  - Social patterning of ill health in Helsinki and Moscow: results from a
      comparative survey in 1991.
AB  - Social inequalities in health are widely documented in the western countries
      including Finland, but research on Russia has so far been scarce. This article
      compares self-reported ill health of men and women and its social patterning in
      Helsinki and Moscow on the basis of a survey. The data (Helsinki N = 824, Moscow
      N = 545) were collected by mailed questionnaires in 1991. The Muscovites fared
      more poorly on perceived and psychological health, but the differences in self
      reported morbidity (prevalence of chronic illnesses) between the cities were
      quite small. The sex differentials were greater in Moscow and Muscovite women had
      the poorest health of all. Education, family income and occupation had the most
      consistent associations with perceived health and morbidity among Helsinki women
      and the weakest among Muscovite women. With few exceptions, men of both cities
      fell between these groups. The differences in health between the cities were
      smaller in groups with low education. Thus, the role of education as a protective
      resource was more pronounced in Helsinki, and more notably among women. The
      possibility of a different impact of social stratification on health in a
      transitional socialist society compared to a western market economy is discussed.

PMID- 9572604
TI  - Community-based trauma systems in the United States: an examination of structural
      development.
AB  - OBJECTIVE: To examine the organizational, political, and community
      characteristics that facilitate or impede community progress in developing a
      coordinative network of health services for trauma delivery. STUDY
      SETTING/DESIGN: A comparative case study design was used to examine trauma
      network development in 6 U.S. cities with a population of 1,000,000 or more. Five
      key coordinative activities were selected for study. Each study site varied in
      the set of activities that had been implemented. DATA SOURCES: Information on the
      structure and composition of local trauma coordinating councils; interviews with
      a common set of informants in each site using a semi-structured interview
      protocol. STUDY METHODS: The literature on interorganizational community
      structures and local policy development was drawn upon to create a conceptual
      framework for assessing the development of a coordinative service network.
      Analytical techniques included network analysis to understand the linkages across
      organizations in overseeing trauma network operations, assessment of leadership
      structures to identify central actors and organizations, and pattern matching
      techniques of case study analysis to identify factors that affected trauma
      network development. PRINCIPAL FINDINGS: Leaders capitalized on local events and
      were instrumental in keeping network development on the top of the political
      agenda. Successful leaders spent substantial time and energy documenting
      problems, assessing the needs and understanding of stakeholders, educating
      stakeholders and politicians, and creating trust and shared understanding of
      values. CONCLUSIONS: Prior research has documented the importance of central
      actors and organizations in developing coordinative networks. The unique
      contribution of our research is its insights on how central actors and
      organizations are more likely to motivate collaboration in situations where they
      lack control over the allocation of payments across involved organizations. Our
      research suggests that under these circumstances central players should focus
      their time and energy educating stakeholders and developing a shared
      understanding rather than using their centrality to impose a particular
      coordinative structure. To date, U.S. trauma networks have served as models for
      other industrialized countries, and thus, lessons learned in the U.S. about
      implementing interorganizational networks of trauma care can assist other
      countries achieve more effective coordination and avoid mistakes that impede
      progress.

PMID- 9572605
TI  - Cancer disclosure in Japan: historical comparisons, current practices.
AB  - Although Japanese physicians historically have not disclosed cancer diagnoses to
      patients, pressures upon physicians to disclose have increased in recent years.
      We questioned physicians practicing at a private medical hospital in rural Japan
      about their current approach to cancer disclosure. We compared their responses
      with responses of physicians in a 1991 study conducted in Japan, and two studies
      conducted in the United States, in 1961 and in 1977. Seventy-seven clinically
      active physicians with experience treating cancer patients responded (73%
      response rate). Forty percent of respondents reported usually telling patients of
      a cancer diagnosis, over three times more than the 13% who reported such a policy
      in Japan in 1991. Physicians were significantly more likely (P < 0.001) to make
      exceptions than physicians in the previous Japanese study, and physicians in the
      previous U.S. studies. Respondents reported considering more factors in deciding
      whether to tell than participants in the 1977 U.S. study. Factors predicting an
      increased probability of disclosure included age (in a hyperbolic relationship),
      improved prognosis, breast or cervical cancer, and social status and religion (by
      a minority of respondents). Increase in a substitute decision maker's age was
      predictive for physicians not to involve the person in decision-making. Most
      respondents reported their disclosure policy is based on clinical experience.
      More respondents indicated a likelihood of changing in the future than
      respondents in the previous U.S. studies. These data suggest Japanese physicians
      are moving away from a rigid policy of nondisclosure to a policy of selective
      disclosure, but they have not adopted universal cancer disclosure as practiced in
      many Western countries. Since young age and advanced age predicted self-reports
      of not disclosing cancer diagnoses, these data raise the question of whether
      nondisclosure by age groups represents age discrimination or compassionate
      medical care tailored to individual patient needs.

PMID- 9572606
TI  - Death, trauma and ritual: Mozambican refugees in Malawi.
AB  - For many non-governmental organizations, the treatment of war trauma among
      refugees has become a key issue in humanitarian assistance. There is, however, as
      yet little independent evaluation of the notions and therapeutic practices which
      inform humanitarian interventions in refugees' mental health. By drawing on
      intensive anthropological fieldwork, the paper problematizes two central issues
      in these interventions: the role of past experiences in refugees' present well
      being, on the one hand, and the need to verbalize trauma in a therapy, on the
      other. An alternative approach to refugees' mental health draws on current
      theoretical insights into non-discursive bodily practices. The paper
      substantiates these insights by focusing on the therapeutic salience of funerals
      and spirit exorcism among Mozambican refugees in Malawi. By exorcizing the
      vengeful spirits of those who had died during the war, refugees were also healing
      their war traumas. It was not so much the loss as the difficulty in observing a
      full range of rituals that characterized refugees' predicament. The paper
      concludes by suggesting ways in which humanitarian assistance could utilize these
      insights.

PMID- 9572607
TI  - Internal structure of a measure of self-efficacy in physical activity among high
      school students.
AB  - The preliminary development of a measure of self-efficacy to participate in
      vigorous physical activity when confronted with specific perceived barriers to
      physical activity is described. Measures used in previous research ([Hofstetter,
      C.R., Hovell, M.F., Sallis, J.F., 1990a. Social learning correlates of exercise
      self-efficacy: Early experiences with physical activity, Social Science and
      Medicine, 31, 1169-1176.]; [Hofstetter, C.R., Sallis, J.F., Hovell, M.F., 1990b.
      Some health dimensions of self-efficacy: Analysis of theoretical specificity,
      Social Science and Medicine, 31, 1051-1056.]; [Reynolds, K.D., Killen, J.D.,
      Bryson, M.S., Maron, D.J., Taylor, C.B., Maccoby, N., Farquhar, J.W., 1990.
      Psychosocial predictors of physical activity in adolescents, Preventive Medicine,
      19, 541-551.]; [Sallis, J.F., Pinski, R.B., Grossman, R.M., Patterson, T.L.,
      Nader, P.R., 1988. The development of self-efficacy scales for health-related
      diet and exercise behaviors, Health Education Research, 3, 283-292.]) were
      adapted and original items were developed. The 20-item measure has a 5-point
      Likert format ranging from not at all confident (1) to very confident (5). An
      earlier pilot study of 200 secondary school students showed that the measure was
      free of social desirability. The data were derived from a survey of 1041
      secondary school students from a Metropolitan Toronto board of education.
      Principal component analysis (PCA) with oblique rotation of the data yielded two
      factors: self-efficacy to overcome external barriers and self-efficacy to
      overcome internal barriers. The 12-item external barriers subscale had a
      coefficient alpha of 0.88 and the 8-item internal barriers subscale had a
      coefficient alpha of 0.87. The subscales significantly correlated with the
      frequency of participation in vigorous physical activity. In summary, the results
      provide some support for the internal consistency reliability, construct
      validity, criterion validity, and discriminant validity of the measure. Though
      further psychometric research is warranted, the self-efficacy measure shows
      promise for physical activity research.

PMID- 9572608
TI  - Cost-effectiveness analysis and capital costs.
AB  - Traditionally, economic evaluations in terms of cost-effectiveness analysis are
      based, explicitly or implicitly, on the assumption of constant returns to scale.
      This assumption has been criticized in the literature and the role of cost
      effectiveness as a tool for decision making has been questioned. In this paper we
      analyze the case of increasing returns to scale due to fixed capital costs. Cost
      effectiveness analysis is regarded as a tool for estimating a cost function. To
      this cost function two types of decision rules can be applied, the budget
      approach and the constant price approach. It is shown that in the presence of
      fixed capital costs the application of these two decision rules to a specific
      patient group will give different results. The budget approach may lead to
      suboptimizations, while using the price as a decision rule will give optimal
      solutions. With fixed capital costs and when an investment can be used for
      treating several patient groups, these groups are no longer independent.
      Therefore the cost-effectiveness analysis has to be performed simultaneously for
      all patient groups that are potential users of the investment.

PMID- 9572609
TI  - Therapeutic landscapes in holistic medicine.
AB  - Therapeutic landscapes are places, settings, situations, locales, and milieus
      that encompass both the physical and psychological environments associated with
      treatment or healing, and the maintenance of health and well-being. Practices
      from holistic medicine--also known as nonconventional, alternative, complementary
      or traditional medicine--are used to illustrate specific humanistic concepts in
      further examining therapeutic landscapes. In addition to contributing to a
      theoretically-informed health geography, this paper further develops the concept
      of therapeutic landscapes and the understanding of holistic medicine.

PMID- 9572611
TI  - Canadian naturopathic practitioners: holistic and scientific world views.
AB  - This paper describes naturopathic practitioners with two different world views-
      holistic and scientific, and explores the relationship of practitioners'
      socialization experiences and practice patterns with these two world views. Data
      were gathered by a variety of methods including: (1) a 14-page questionnaire
      mailed to all 296 naturopathic practitioners licensed in Canada; (2) a
      participant observation study at the Canadian College of Naturopathic Medicine
      (CCNM); and (3) open-ended interviews with 16 students attending CCNM and 41
      naturopathic practitioners which were audio-taped and transcribed verbatim.
      Individuals with both holistic and scientific world views entered naturopathic
      training and none of the practitioners who were interviewed reported a change in
      world view while at naturopathic college. However, practitioners reported a new
      found appreciation of the "other" world view on completion of their training,
      indicating the occurrence of a socialization effect. Many decisions involved in
      setting up a practice and seeing patients were affected by the practitioners'
      world views. For example, there were distinct differences in the way the
      practitioners with different world views who were interviewed chose treatment
      modalities. Practitioners with scientific world views reported choosing
      treatments based on the available "scientific evidence", while practitioners with
      holistic world views included a careful exploration of the patient's spirituality
      and their own intuition in their treatment decisions. In addition, practitioners
      with holistic world views reported significantly longer patient visits than
      practitioners with scientific world views. The data presented here suggest that
      one's world view influences one's perceptions of socialization experiences and
      social situations, and modulates the effects of both on practice patterns.

PMID- 9572610
TI  - The accuracy of mothers' reports of child vaccination: evidence from rural Egypt.
AB  - Estimates of immunization coverage in developing countries are typically made on
      a "card plus history" basis, combining information obtained from vaccination
      cards with information from mothers' reports, for children for whom such cards
      are not available. A recent survey in rural lower Egypt was able to test the
      accuracy of mothers' reports for a subset of children whose cards were not seen
      at round 1 of the survey but were seen a year later at round 3. Comparisons of
      the unsubstantiated reports at round 1 with information recorded from cards seen
      at round 3 indicate that mothers' reports are of very high quality; mothers'
      reports at round 1 were confirmed by card data at round 3 for between 83 and 93%,
      depending on vaccine, of children aged 12-23 months, and for 88 to 98% of
      children aged 24-35 months. Mothers of children who had not been vaccinated were
      more likely to give consistent responses than were mothers of vaccinated
      children. Thus, these "card plus history" estimates slightly understate true
      coverage levels. Most of the inconsistencies between round 1 and round 3 data
      apparently arose from interviewer or data processing error rather than from
      misreporting by mothers.

PMID- 9572612
TI  - Firearm suicides and homicides in the United States: regional variations and
      patterns of gun ownership.
AB  - Among industrialized countries, the United States has the highest rates of
      firearm suicide and homicide, as well as the highest rate of gun ownership. The
      present study compares the differential impact of gun availability on firearm
      suicides and homicides in the U.S. Using data from the NCHS Mortality Detail
      Files (1989-1991), the 1990 U.S. census population estimates, and the General
      Social Surveys (1989-1991) for nine geographic divisions, we computed rates of
      firearm and non-firearm suicides and homicides as well as rates of gun ownership
      for four gender-race groups. We tested the strength of the associations between
      gun availability and firearm suicide and homicide rates by computing the Spearman
      correlation coefficients. To help elucidate the role of method substitution, we
      conducted similar analyses on non-firearm suicide and homicide. The results show
      that gun ownership has a stronger impact on firearm suicides than homicides.
      These findings held up after stratifying by gender and race. The study suggests
      that reducing the aggregate level of gun availability may decrease the risk of
      firearm-related deaths.

PMID- 9572613
TI  - Gender, social mobility and psychiatric diagnoses.
AB  - Data from a Swedish cohort born in 1953 and studied through to 1983 is used to
      examine the relationship between the incidence of psychiatric disorder, parental
      socio-economic status and intergenerational social mobility. No difference is
      found in the over-all incidence of in-patient treatment between men and women,
      but there are considerable differences in the incidence of individual diagnoses.
      As found in other studies, rates of schizophrenia and substance abuse are greater
      among men than women, while rates of neurosis are greater among women. The data
      generally support the drift explanation of inequalities in health rather than the
      social causation hypothesis, but there is some variation by both gender and
      diagnosis. Little association is found between parental status, measured when
      cohort members were aged 10, and the incidence of disorder, except in the case of
      substance abuse, but there is a strong association between disorder and own
      status, measured at age 27 yr. By far the highest rates of disorder are found
      among those members of the cohort who are not in the workforce. Both
      schizophrenia and neurosis exhibit strong drift effects; there is some evidence
      that the children of higher status parents have a heightened risk of being
      diagnosed as schizophrenic; in the case of substance abuse both downwards social
      mobility and low class origins appear to be implicated in the cumulative
      incidence of in-patient treatment.

PMID- 9572614
TI  - Is curative radiation therapy in elderly patients limited by increased normal
      tissue toxicity?

PMID- 9572615
TI  - Measuring hypoxia and predicting tumor radioresistance with nuclear medicine
      assays.
AB  - Tumor cells at low oxygen tension are relatively radioresistant. The hypoxic
      fraction of individual tumors before, during and after radiotherapy is likely to
      have prognostic value but its diagnosis still awaits an accurate and acceptable
      assay. The recent indications that hypoxia can also induce the expression of
      specific genes and promote a more aggressive tumor phenotype makes its diagnosis
      even more important. Over 15 years ago, misonidazole, an azomycin-based hypoxic
      cell radiosensitizer, was found to link covalently to cellular molecules at rates
      inversely proportional to intracellular oxygen concentration. The use of
      bioreducible markers to positively label zones of viable hypoxic cells within
      solid tumors and to predict for tumor radioresistance was proposed. Several
      hypoxic markers have now been identified and their selective binding within
      tumors has been measured by both invasive and non-invasive assays. Research from
      our laboratory has emphasized both mechanistic and preclinical studies associated
      with nuclear medicine procedures for measuring tumor hypoxia and predicting tumor
      radioresistance. This report updates radiation oncologists about the status of
      nuclear medicine hypoxic marker research and development as of mid-1997. While
      several potential imaging agents have been identified, their testing and
      validation in appropriate human tumors will require focused research efforts by
      individual academic departments and, possibly, by clinical trials performed
      through cooperative groups. Since the prediction of hypoxia in individual tumors
      could strongly impact radiotherapy treatment planning, the radiation oncology
      research community is best positioned to execute the validation studies
      associated with these markers.

PMID- 9572616
TI  - Age has no impact on acute and late toxicity of curative thoracic radiotherapy.
AB  - BACKGROUND AND PURPOSE: Radiotherapy is a treatment method frequently employed in
      the management of thoracic tumours. Although the highest incidence of these
      tumours is found in elderly people, tolerance to radiotherapy is not well
      documented in older age groups. Many physicians are tempted to alter the
      radiotherapy planning in a population with a supposed lower life expectancy in
      order to prevent acute reactions whereas late reactions are often ignored. The
      current study aimed to determine the influence of age on the frequency and
      severity of acute and late side-effects and also whether the prognosis of tumours
      sufficiently differed between ages to justify different attitudes towards their
      management. MATERIALS AND METHODS: Data from 1208 patients receiving chest
      irradiation and included in arms designed with RT of six EORTC randomized trials
      were evaluated. Data were extracted by a computer program elaborated for each
      study and were merged in a single database for analysis. Patients were split into
      six age ranges from 50 to 70 years and over. Survival and late toxicity were
      calculated with the Kaplan-Meier method and comparison between age groups was
      performed with the logrank test. The gamma-statistic test was used to test the
      impact of age on acute toxicity occurrence. RESULTS: Survival adjusted for the
      primary location of the tumour was comparable in each age group (P = 0.82). Data
      regarding age and acute toxicity were available for 1208 patients who experienced
      640 grade > or =1 toxicities. The difference in distribution over age was not
      significant for acute nausea, dyspnea, oesophagitis, weakness and WHO performance
      status alteration. Weight loss was significantly different with regards to age
      with a trend toward increased weight loss in older age groups (P = 0.002). To
      minimize actuarial bias, only patients surviving more than 90 days were analyzed
      for late effect risks. Late toxicities were examined only if they occurred before
      an eventual tumour failure in order to avoid confusion between effects of first
      and second line treatments. In such conditions, 1082 grade > or =1 late
      toxicities were recorded in 935 patients of 1106 available for analysis. The mean
      time to complication was 13 months and was similar in all age groups. Forty
      percent of patients were free of complication at 4 years, the logrank test
      showing no significant difference between age groups (P = 0.57). For grade >2
      side-effects, the calculation did not show any difference between each age group
      (P = 0.1). A detailed analysis of late dyspnea and late weakness studied with the
      same method did not demonstrate any difference between age groups. Only grade >2
      late oesophagitis demonstrated a significant trend to be more frequent in older
      patients (P = 0.01), but this difference disappeared after adjustment on study (P
      = 0.32). CONCLUSION: The absence of toxicity observed in the current study
      regardless of age reinforces the conviction that age per se is not a sufficient
      reason to exclude patients in good general condition with thoracic tumour from
      curative radiotherapy when medically indicated.

PMID- 9572617
TI  - Treatment of anal canal carcinoma with high dose radiation therapy and
      concomitant fluorouracil-cisplatinum. Long-term results in 95 patients.
AB  - PURPOSE: To evaluate the long-term results of the treatment of anal canal
      carcinoma (ACC) with a combined concomitant radiochemotherapy (CCRT) treatment
      using fluorouracil (5 FU) and cisplatinum (CDDP) with a high dose of radiation
      therapy. PATIENTS AND METHODS: Between 1982 and 1993 a series of 95 patients were
      treated. Staging showed a majority of advanced squamous ACC, i.e. 6 T1, 47 T2, 28
      T3, 14 T4, 53 NO, 32 N1, 6 N2 and 4 N3. Irradiation was done with high dose
      external beam radiation therapy (EBRT) followed by a boost with 192 Iridium
      implant. During EBRT all patients received one course of 5 FU continuous infusion
      (1 g/m2/day, days 1-4) and CDDP (25 mg/m2/day, bolus days 1-4). RESULTS: The
      median follow-up time was 64 months. At 5 and 8 years the overall survival was 84
      and 77%, the cancer specific survival was 90 and 86% and the colostomy-free
      survival was 71 and 67%, respectively. The stage and the response of the tumor
      after EBRT were of prognostic significance. Patients with pararectal lymph nodes
      had an overall 5-year survival of 76% (versus 88% for non-N1). Among 78 patients
      who preserved their anus, the anal sphincter function was excellent or good in 72
      (92%). CONCLUSION: According to these results and recent randomized trials, CCRT
      appears as the standard treatment of ACC. Radical surgery should be reserved for
      local recurrence or persisting disease after irradiation. High dose irradiation
      in a small volume with concomitant 5 FU-CDDP appears to give a high rate of long
      term local control and survival. Careful evaluation of pararectal nodes is
      essential for a good staging of the disease.

PMID- 9572618
TI  - Alternating radiotherapy and chemotherapy in limited disease small cell lung
      cancer.
AB  - In a pilot study of 29 patients treated for localized small cell lung cancer,
      three new approaches were introduced, i.e. an increased initial drug dose, an
      early alternation of chemotherapy and thoracic radiotherapy and initial
      accelerated and hyperfractionated irradiation. The results were interesting.
      However, a high rate of fatal toxicity (21%) was observed.

PMID- 9572619
TI  - Radiotherapy of choroidal metastases.
AB  - PURPOSE: This retrospective study was undertaken to clarify the role of high
      energy external beam radiation therapy (EBRT) and to determine its safety and
      efficacy on local control and visual acuity in patients suffering from choroidal
      metastases (CM). MATERIALS AND METHODS: The records of 58 consecutive patients
      treated with EBRT between 1970 and 1993 were analyzed. The female to male ratio
      was 2.9 and the median age was 59 years (range 40-81 years). Thirty-six patients
      (62%) had unilateral CM and 22 patients had bilateral CM. The mean number of
      lesions per eye was two. Retinal detachment was present in 65% of cases. The
      primary tumour (PT) was breast carcinoma for 38 patients (75%), lung carcinoma
      for 10 patients (17%) and gastrointestinal, genitourinary or unknown PT for the
      remaining 10 patients. The median interval of time between the PT and the CM was
      55 months (range 0-228 months). All patients were treated with megavoltage
      irradiation. The median prescribed dose was 35.5 Gy (range 20-53 Gy) normalized
      at a 2 Gy per fraction schedule with an alpha/beta value of 10 Gy. Various
      techniques were used and whenever possible the lens was spared. Ten patients with
      unilateral disease were treated in both eyes. RESULTS: The tumour response was
      slow. When assessed after 3 months or more, the complete response rate was 53%
      with significantly better results for doses higher than 35.5 Gy (72 versus 33%; P
      = 0.009). Visual acuity was improved or stabilized in 62% of patients, with also
      significantly better results when doses higher than 35.5 Gy (P = 0.014) were
      administered. Amongst 26 patients with unilateral CM who had no elective
      contralateral irradiation, three developed metastasis in the opposite eye versus
      none of the 10 patients who had bilateral irradiation. Five complications
      occurred (three cataracts, one retinopathy and one glaucoma). CONCLUSION:
      Radiation therapy is an efficient and safe palliative treatment for choroidal
      metastases and it helps the preservation of vision. Thus, there is a major impact
      on the quality of life in a group of patients with an almost uniformly fatal
      prognosis. Both tumour response and visual acuity are significantly improved if
      doses higher than 35.5 Gy are administered. Whenever possible, a lens sparing
      technique should be used.

PMID- 9572620
TI  - New insights into factors influencing the clinically relevant oxygen enhancement
      ratio.
AB  - BACKGROUND AND PURPOSE: This paper deals with the variations in the oxygen
      enhancement ratios that could be observed (OER') when comparing oxic and hypoxic
      cells in different types of fractionated experiments as a consequence of the non
      linearity of the underlying cell survival curves. Calculations have been made of
      the OER' that would be obtained for fractionated irradiations with a series of
      small doses to allow the comparison of isoeffective doses in oxic and hypoxic
      conditions. Two styles of fractionated experiment were modelled. In one, the dose
      per fraction was kept constant in the oxic and hypoxic arms of the experiment,
      necessitating more fractions in hypoxia to achieve the same level of cell kill.
      In the other the number of fractions was kept constant and the fraction size was
      varied to obtain equal levels of damage. The first is the relevant design for the
      clinic, whereas the second is the design most commonly used in animal studies.
      MATERIALS AND METHODS: Three models of the survival curve were used to simulate
      the response of cells to radiation injury, all based on the linear quadratic
      model, but with various added assumptions. A simple classical LQ model is
      compared with two models in which the concept of inducible repair is added. In
      one of these the induction dose for 'switching on' the more resistant response is
      assumed to be increased in hypoxia and in the other it is assumed to be
      independent of the oxygen tension. RESULTS: These calculations show a clear and
      previously unsuspected dependence of the measured OER' on the design of the
      fractionated experiment. The values obtained in the clinical and animal types of
      study differ considerably with all three models. The direction and magnitude of
      that difference depends critically on the assumptions about the fine structure of
      the survival curve shape. The authors suggest that the inducible repair version
      with an oxygen-dependent induction dose is probably the most relevant model.
      Using this, the measured OER' is reduced at doses around 2 Gy for the clinically
      relevant design of constant sized fractions to the oxic and hypoxic cells. It may
      even, in certain model assumptions, fall below unity resulting in an increased
      sensitivity, not resistance, from the hypoxia. CONCLUSIONS: These calculations
      indicate the urgent need for more knowledge about the fine structure of the low
      dose region of the survival curves for human tumour cells and especially for
      comparisons in the presence and absence of oxygen. The extent of the
      hypersensitivity at very low doses, the trigger dose needed to induce the repair
      and its oxygen modification may be dominant factors in determining the response
      of tumour cells to clinically relevant fractionation schedules.

PMID- 9572621
TI  - Combined effects of ionizing radiation and 4-hydroperoxyfosfamide in vitro.
AB  - BACKGROUND AND PURPOSE: Combined radiochemotherapy has gained increasing interest
      in clinical applications. The effects of combined exposure of ionizing radiation
      and 4-hydroperoxyifosfamide (4HOOIF) on cell survival were investigated in vitro.
      MATERIALS AND METHODS: Clonogenic survival of log phase V79, Caski (squamous
      carcinoma), Widr (colon carcinoma) and MRI-221 cells (human melanoma) was
      determined after combined exposure to 4HOOIF and radiation. Measurement of cell
      survival for different cell cycle phases was performed after mitotic shake-off
      (V79) or appropriate intervals after serum stimulation of plateau phase cells
      (Widr). Control of cell cycle distribution was performed using flow cytometry.
      RESULTS: In all cell lines tested, a combined exposure resulted in cell killing
      that was greater than for independent action. While this type of
      radiosensitization was of minor magnitude for log-phase cells or cells in G1
      substantial radiosensitization was detected for S-phase cells with enhancement
      ratios (calculated from the respective mean inactivation doses) of up to 1.5.
      CONCLUSIONS: The results demonstrate the interaction of 4HOOIF and radiation
      induced cell damage with marked cell cycle specificity. Since the largest
      combination effect was observed for the most radioresistant S-phase cells, damage
      interaction could be mediated by an interference of 4HOOIF with the
      repair/fixation pathway of radiation-induced potentially lethal damage.

PMID- 9572622
TI  - The linear-quadratic transformation of dose-volume histograms in fractionated
      radiotherapy.
AB  - BACKGROUND AND PURPOSE: Dose-volume histograms (DVHs) are often used in
      radiotherapy to provide representations of treatment dose distributions. DVHs are
      computed from physical dose and do not include radiobiological factors;
      therefore, the same DVH will be computed for a treatment plan whatever
      fractionation regimen is used. However, dose heterogeneity resulting from
      variation of daily treatment dose within the volume will have biological effects
      due to spatial heterogeneity of fraction size as well as total dose. The purpose
      of the paper is to present a radiobiological (LQ) transformation of the physical
      dose distribution which incorporates fraction size effects and may be better
      suited to the prediction of biological effects. METHODS: An analytic formula is
      derived for the linear-quadratic transformation of a normal distribution of dose
      to give the corresponding distribution of biologically equivalent dose given as 2
      Gy fractions. This allows LQ-transformed DVHs to be computed from physical DVHs.
      The resultant LQ-DVH depends on the assumed value of the relevant alpha/beta
      ratio. It is a modified dose distribution (corrected for spatial heterogeneity of
      fraction size) but does not incorporate time factors or volume effects. RESULTS:
      The analysis shows that the LQ-transformed distribution is always broader than
      the distribution of physical dose. Radiobiological 'hot spots' and 'cold spots'
      are further from the mean than physical distributions would indicate. The
      difference between conventional DVHs and LQ-transformed DVHs is dependent on the
      fractionation regimen used. LQ-DVHs for a single dose distribution (treatment
      plan) can be computed for different fractionation regimens with some simplifying
      assumptions (e.g. no time-factor-dependence of late effects). Regimens calculated
      to be radiobiologically equivalent at a single point nevertheless result in non
      equivalent LQ-DVHs when spatial variation of daily treatment dose is included.
      The difference is especially important for tumour sites (such as breast and head
      and neck) for which considerable dose heterogeneity may occur and for which
      different treatment regimens are in use. CONCLUSIONS: LQ-DVHs should be computed
      in parallel with conventional DVHs and used in the evaluation of treatment plans
      and fractionation regimens and in the analysis of high-dose side-effects in
      patients.

PMID- 9572623
TI  - Volume effects in the irradiated canine spinal cord: do they exist when the
      probability of injury is low?
AB  - PURPOSE: The purpose of this study was to investigate volume effects in the
      irradiated canine spinal cord. MATERIALS AND METHODS: Eighty-nine beagle dogs
      were given 44-84 Gy photons in 4 Gy fractions to 4 or 20 cm lengths of thoracic
      spinal cord. As controls, 36 dogs were given 60-84 Gy in 2 Gy fractions to a 20
      cm length of spinal cord and six dogs were unirradiated. Dogs were evaluated for
      clinical signs, and after euthanasia, for occurrence of gross lesions, severe
      lesions of massive hemorrhage, white matter necrosis and/or parenchymal atrophy
      and mild lesions of focal fiber loss. White matter vacuoles, meningeal thickness
      and dorsal root ganglia lesions were quantified. Data were analyzed to test for
      an effect of volume on dose-response curves. RESULTS: Significant volume effects
      were found between 4 and 20 cm lengths of irradiated spinal cord for gross
      lesions, severe lesions and mild lesions (8.3-15.0 Gy difference at the ED50
      level). The ED50 in 4 Gy fractions for severe lesions was 56.9 Gy (95% CI 53.1
      60.6) for 20 cm and 68.8 Gy (95% CI 64.5-75.1) for 4 cm fields. Significant
      improvements in the fit of data to dose-response curves resulted when using
      models with either parallel or non-parallel curves, but in either case an
      appreciable difference existed between curves at low probabilities of injury.
      Volume effects were present for meningeal thickness and slopes of dose-response
      curves were different. Clinical signs correlated well with severe lesions for 20
      cm (ED50 = 54.0 Gy), but not for 4 cm fields (ED50 = 77.6 Gy). CONCLUSIONS:
      Volume effects exist for the occurrence of pathologic lesions in irradiated
      canine spinal cord. Clinical compensation for pathologic lesions occur at small,
      but not large irradiated volumes. There is insufficient data to support a
      decreased slope of dose-response curves with decreased volume. Volume effects
      estimated at the 50% level of spinal cord injury could also hold at low
      probabilities of injury characteristic of the clinic.

PMID- 9572624
TI  - Radiation nephropathy is treatable with an angiotensin converting enzyme
      inhibitor or an angiotensin II type-1 (AT1) receptor antagonist.
AB  - BACKGROUND AND PURPOSE: Previous studies showed that progression of established
      radiation nephropathy could be delayed by continuous treatment with high doses of
      captopril, an angiotensin-converting-enzyme (ACE) inhibitor. The current studies
      were designed to determine whether a lower dose or a shorter treatment with
      captopril would be effective and whether an angiotensin II type-1 (AT1) receptor
      antagonist (AII blocker) would be effective. MATERIALS AND METHODS: In the
      captopril studies, rats were given renal irradiation at doses sufficient to
      produce radiation nephropathy. Six months after irradiation, animals were
      stratified by azotemia and assigned to no treatment, continuous high- or low-dose
      captopril, or 6 weeks of high-dose captopril. Captopril was given in drinking
      water at 62.5 mg/l (low dose) or 500 mg/l (high dose). The AII blocker study had
      a similar design, except that the nephropathy was the result of total body
      irradiation and bone marrow transplantation and the treatments were no treatment
      or continuous treatment with an AII blocker, L-158,809 (20 mg/l in drinking
      water). Animals were followed for 1 year with periodic studies of renal function.
      RESULTS: Survival and renal function were significantly enhanced by all
      treatments. Continuous captopril treatment was more effective than the 6-week
      course of treatment, but there was no difference in effectiveness between the
      high and low doses of captopril. In continuous therapy, captopril and the AII
      blocker had roughly equivalent efficacy. CONCLUSIONS: Both the ACE inhibitor and
      the AII blocker were effective treatments for established radiation nephropathy.
      The best results with the ACE inhibitor required continuous therapy, but could be
      achieved with a low dose of the drug.

PMID- 9572626
TI  - A fast and accurate treatment planning method for boron neutron capture therapy.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to test the applicability of
      conventional semi-empirical algorithms for the treatment planning of boron
      neutron capture therapy (BNCT). MATERIALS AND METHODS: Beam data of a clinical
      epithermal BNCT beam obtained in a large cuboid water phantom were introduced
      into a commercial treatment planning system (TPS). For the calculation of thermal
      neutron fluence distributions, the Gaussian pencil beam model of the electron
      beam treatment planning algorithm was used. A simple photon beam algorithm was
      used for the calculation of the gamma-ray and fast neutron dose distribution. The
      calculated dose and fluence distributions in the central plane of an
      anthropomorphic head phantom were compared with measurements for various field
      sizes. The calculation time was less than 1 min. RESULTS: At the normalization
      point in the head phantom, the absolute dose and fluence values agreed within the
      measurement uncertainty of approximately 2-3% (1 SD) with those at the same depth
      in a cuboid phantom of approximately the same size. Excellent agreement of within
      2-3% (1 SD) was obtained between measured and calculated relative fluence and
      dose values on the central beam axis and at most off-axis positions in the head
      phantom. At positions near the phantom boundaries, generally in low dose regions,
      local differences of approximately 30% were observed. CONCLUSIONS: A fast and
      accurate treatment planning method has been developed for BNCT. This is the first
      treatment planning method that may allow the same interactive optimization
      procedures for BNCT as applied clinically for conventional radiotherapy.

PMID- 9572625
TI  - Combined modality treatment of bone metastases: response of the rhabdomyosarcoma
      R1H of the rat to postoperative irradiation combined with local release of
      daunorubicin from acrylic cement.
AB  - Reconstruction techniques for pathological fractures caused by bone metastases
      often include acrylic cement to stabilise defects. The aim of this study was to
      test in a rodent model, whether outcome could be improved by local chemotherapy
      from an anticancer drug added to the acrylic cement. Tumour excision 17 days
      after transplantation into the femur was followed by fractionated irradiation.
      Supplementation of acrylic cement with daunorubicin led to a considerable
      reduction of TCD37% from 72.9 Gy (62.2-82.8) to 29.3 Gy (21.8-37.5) (P = 0.0007).
      Local chemotherapy diffusing from bone cement combined with postoperative
      radiotherapy was highly effective in the experimental system studied.

PMID- 9572627
TI  - Biological equivalence of stepping source versus wire source dosage according to
      the LQ model.

PMID- 9572628
TI  - The treatment of bladder cancer in the elderly.

PMID- 9572630
TI  - One thousand days until the target date for global poliomyelitis eradication.
AB  - On April 6, only 1000 days will remain until the end of 2000, the target date
      established by the World Health Assembly in 1988 for the eradication of
      poliomyelitis and included as a year 2000 goal by the World Summit for Children
      in 1990. Progress toward this goal has included elimination of endemic polio from
      the Western Hemisphere in 1991 and apparent elimination of endemic transmission
      in 1997 from both the Western Pacific and European (except Turkey and Tajikistan)
      regions of the World Health Organization (WHO). In addition, globally, reported
      polio cases have decreased >90% since 1988. These accomplishments underscore the
      feasibility of global eradication. All countries with endemic polio, except for
      Democratic Republic of Congo, Liberia, Sierra Leone, and Somalia, have conducted
      National Immunization Days, one of the key strategies advocated by WHO to achieve
      polio eradication.

PMID- 9572629
TI  - Tobacco use among high school students--United States, 1997.
AB  - Tobacco use is the single leading preventable cause of death in the United
      States. Approximately 80% of tobacco use occurs for the first time among youth
      aged <18 years, and the prevalence of cigarette smoking among adolescents
      increased during the early 1990s. To determine prevalence rates of cigarette,
      smokeless tobacco (chewing tobacco or snuff), and cigar use for U.S. high school
      students, CDC analyzed data from the 1997 Youth Risk Behavior Survey (YRBS). This
      report summarizes the results of the analysis, which indicate that the prevalence
      of current cigarette smoking among U.S. high school students increased from 27.5%
      in 1991 to 36.4% in 1997 and that, in 1997, 42.7% of students used cigarettes,
      smokeless tobacco, or cigars during the 30 days preceding the survey.

PMID- 9572631
TI  - Progress toward poliomyelitis eradication--African Region, 1997.
AB  - In 1988, the World Health Assembly established the goal of eradicating
      poliomyelitis worldwide by 2000. To achieve this goal, the World Health
      Organization (WHO) promotes the implementation of specific strategies.
      Eradicating polio from the African continent is one of the remaining major
      challenges to achieving global eradication by the target date. This report
      summarizes progress in the African Region of WHO in 1997 with the implementation
      of polio eradication strategies, and suggests that polio eradication by 2000
      remains a feasible target.

PMID- 9572632
TI  - State differences in reported healthy days among adults--United States, 1993
      1996.
AB  - Traditional population health measures, such as infant mortality rates,
      vaccination rates, and average life expectancy, have emphasized morbidity and
      mortality. During the past decade, weighted indices of population health (e.g.,
      years of healthy life and disability-adjusted life-years), which combine life
      expectancy with aspects of health-related quality of life (HRQOL), have provided
      more comprehensive summary measures. To meet the need for a less complex measure
      that is more sensitive to local variations in population health, CDC developed
      the "healthy days" index. This HRQOL index tracks the number of healthy days
      (i.e., days when persons' physical and mental health were both good) during the
      preceding 30 days for a specific population. This report describes state
      differences for 1993-1996 in the mean number of healthy days reported by adults,
      including large differences within each state by level of formal education.

PMID- 9572633
TI  - Familial Mediterranean fever: from the clinical syndrome to the cloning of the
      pyrin gene.
AB  - Familial Mediterranean fever (FMF) is a genetic disorder, restricted to peoples
      originating in the Middle East. The clinical syndrome is characterized by
      shortlived febrile episodes, accompanied by inflammation in one of the serous
      membranes, resulting in peritonitis pleuritis or synovitis. In many untreated FMF
      patients, systemic amyloidosis developed. The clinical presentation of
      amyloidosis in FMF is nephropathic, progressing from proteinuria, nephrosis to
      renal failure and end stage renal disease. Continuous colchicine treatment, which
      was introduced in 1972, prevents most febrile-inflammatory attacks of FMF, and
      inhibits the development of amyloidosis in this otherwise fatal disease.
      Recently, the gene that causes FMF was cloned. It is called the pyrin gene and
      encodes the pyrin protein. Five missense mutations were found so far in the gene.
      These give rise to 5 amino acid substitutions, all of them in the carboxyterminal
      part of the pyrin protein. The pyrin protein is expressed solely in neutrophiles
      white blood cells which are found in large numbers in the inflammatory sites
      during FMF attacks. It seems that the role of the wild type of the pyrin protein
      is to inhibit inflammation that can be provoked by a minor insult. The mutated
      pyrin protein in FMF is probably unable to inhibit these unnecessary inflammatory
      events. Preliminary studies of phenotype genotype correlation are reported.

PMID- 9572634
TI  - Systemic lupus erythematosus in Denmark: clinical and epidemiological
      characterization of a county-based cohort.
AB  - A population based cohort of patients with systemic lupus erythematosus (SLE) was
      recruited from a for epidemiological purposes representative Danish region.
      Patients were ascertained from 4 different sources with a high degree of
      completeness as estimated by using capture-recapture analysis. The diagnosis was
      verified by means of case records, patient interviews, and clinical examinations.
      Patients were classified according to the 1982 revised ACR criteria as Definite
      SLE (D-SLE) fulfilling > or = 4 criteria and Incomplete SLE (I-SLE) with < 4
      criteria. As of January 1, 1995, the point prevalences of D-SLE and I-SLE were
      21.7 and 5.2 per 100000 respectively. The cohort comprised 98% white Europeans.
      The annual incidence of D-SLE increased from 1.0/100,000 to 3.6/100,000 during
      the study period 1980-94. D-SLE patients had clinical profiles comparable to
      other Western European study populations. The I-SLE subclass had milder disease
      manifested by lower criterial load and absence of cerebral and kidney
      involvement. Tissue and organ damage expressed as SLICC-score increased in the
      order of live I-SLE, live D-SLE, and deceased patients.

PMID- 9572635
TI  - The effect of glucocorticoids on fat and lean tissue masses in giant cell
      arteritis.
AB  - The aim of the present prospective study over a follow-up period of two years was
      to assess the influence of various doses of glucocorticosteroids on the total
      body fat and lean tissue masses and their regional distribution, using DXA
      technique, in twenty-four patients with giant cell arteritis (GCA). Treatment
      with glucocorticoids for two years, using high doses of prednisolone the first
      six months and lower doses thereafter, resulted in a significant increase in
      total body fat as well as in trunk fat expressed either as absolute values or as
      a proportion of body weight. The abnormal accumulation of fat mass remained also
      after switching to a low dose glucocorticoid schedule. There was no
      redistribution of fat from peripheral areas to central parts of the body and
      there was no depletion of lean tissue at peripheral sites.

PMID- 9572636
TI  - A placebo controlled crossover trial of subcutaneous salmon calcitonin in the
      treatment of patients with fibromyalgia.
AB  - The objective of this study was to evaluate the relative efficacy and
      tolerability of subcutaneously (s.c.) administered salmon calcitonin (sCT) in the
      treatment of patients with fibromyalgia. Eleven patients who fulfilled the
      American College of Rheumatology classification criteria for fibromyalgia were
      studied in a double-blind, crossover trial in which they alternatively received
      salmon calcitonin (100 IU s.c.) and isotonic saline (1 cc s.c.) for four weeks,
      with a four weeks wash-out period between the treatments. None of the 11 outcomes
      measures (seven analog scales, dolorimetry score, and three SIP scores) showed a
      significant improvement with sCT. The principal side effect observed with sCT was
      nausea in ten patients and erythema in four patients. These data suggest that sCT
      given at a dose of 100 IU daily for one month is not effective in the treatment
      of fibromyalgia.

PMID- 9572637
TI  - Evaluation of a structured multidisciplinary day care program in rheumatoid
      arthritis. A similar effect in newly diagnosed and long-standing disease.
AB  - The present study evaluated a multidisciplinary structured day-care programme in
      patients with rheumatoid arthritis of less than 2 years (n = 41) and more than 2
      years disease duration (n = 46). During the 3 week intervention, outcome measures
      reflecting disability (HAQ, SOFI), the patient's perception of disease and pain
      (VAS for patient's global assessment and pain), Ritchie articular index (RAI), a
      44 swollen joint count, and overall disease activity (DAS) improved significantly
      in the group as a whole. The improvements remained significant after 15 weeks and
      were of a similar magnitude in the patient groups with short and long disease
      duration. At week 3 and 15, the ACR and the EULAR criteria for individual
      response, for the total study group was fulfilled by 28% and 26%, and 36% and 52%
      respectively. Evaluation of a subgroup 6 weeks prior to admission indicated that
      the outcome measures were stable at the time of the intervention. Furthermore,
      administration of intraarticular glucocorticosteroids (GC) could only partly
      explain the observed improvement. This uncontrolled observational study supports
      that a multidisciplinary day-care rehabilitation program is beneficial and
      feasible for patients with rheumatoid arthritis of both short and long duration.

PMID- 9572638
TI  - Weighting for joint surface area improves the information provided by a reduced
      28-joint articular index of swollen joints.
AB  - The objective of our study was to examine whether weighting for joint surface
      area or recording of simultaneously tender and swollen joints increases the
      association of a reduced 28-joint articular index with clinical and outcome
      parameters. In a cross-sectional study we examined 61 consecutive outpatients
      with RA fulfilling the American Rheumatism Association 1987 revised criteria.
      Tender, swollen, and simultaneously tender and swollen joints were recorded. The
      association of 28- and 68-joint articular indices with clinical and outcome
      parameters were estimated with nonparametric correlation analyses. Weighting for
      joint surface yielded consistently increased correlation of clinical and outcome
      parameters with swollen and tender and swollen but not with tender joint counts.
      The correlation of the 28-joint articular and 68-articular indices with these
      parameters were similar. In conclusion, weighting for joint surface notably
      improves the information provided by swollen joint counts, whereas it does not
      appear to improve the information provided by tender joint counts.

PMID- 9572639
TI  - Double-negative (CD4-CD8-) TCRalphabeta+ cells in patients with systemic lupus
      erythematosus.
AB  - Massive accumulation of CD4-CD8-TCRalphabeta+ cells in secondary lymphoid organs
      is characteristic of lupus-prone MRL/lpr mice. However, the role of these double
      negative T cells (DNT) in human lupus patients receive only limited attention.
      Herein, we investigate the frequency of DNT in the peripheral blood mononuclear
      cells of forty seven Chinese patients with systemic lupus erythematosus (SLE) and
      forty four normal individuals. DNT were measured with dual-fluorescence flow
      cytometry. The results showed that DNT only constituted a very minor subset of
      lymphocytes both in patients and normals, it normally did not exceed 2% of the
      lymphocyte population. Compared with normal subjects, patients with SLE had
      slightly increased levels of DNT within the total lymphocyte population (0.66+/
      0.45% vs 0.51+/-0.33%) or within TCRalphabeta+ population (1.14+/-0.88% vs 0.88+/
      0.54%). The difference, however, did not reach statistical significance. The
      levels of DNT correlated neither with the titers of anti-DNA antibodies in sera
      nor with the presence of active and severe lupus nephritis in SLE patients.
      Longitudinal follow-up of six patients at the stages of active and inactive
      nephritis revealed similar levels of DNT in the same individual. The preliminary
      results suggest that circulating DNT do not appear to play a critical role in
      Chinese patients with SLE.

PMID- 9572640
TI  - Substance P receptor (NK1) gene expression in synovial tissue in rheumatoid
      arthritis and osteoarthritis.
AB  - The distribution of messenger RNA coding for substance P receptor (NK1) in
      rheumatoid synovia and the relationship between signal intensity of NK1 mRNA and
      clinical parameters of disease activity were investigated. The synovia from 10
      patients with rheumatoid arthritis (RA) and 7 patients with osteoarthritis was
      investigated by in situ hybridization histochemistry. In rheumatoid synovia,
      strong hybridization signal of NK1 mRNA was detected in 80% of the cells in both
      the lining layer and the interstitial layer. Moreover, the signal intensities of
      NK1 mRNA positively correlated with serum C-reactive protein levels and
      radiographic grade of joint destruction. These results provide histochemical
      evidence that rheumatoid synoviocytes strongly express NK1 gene, and the positive
      relation of the signal intensity of NK1 mRNA with CRP and radiographic severity
      suggests that the facilitation of NK1 gene expression in rheumatoid synovium
      relate the disease progression of RA.

PMID- 9572641
TI  - IL-10 gene promoter polymorphisms in rheumatoid arthritis.
AB  - IL-10 is an anti-inflammatory cytokine which may modulate disease expression in
      RA. Three dimorphic polymorphisms within the IL-10 gene promoter have recently
      been identified and appear to influence regulation of its expression. The 1082*A
      allele has been associated with low and the 1082*G allele with high in vitro IL
      10 production. We have analysed 117 unrelated Caucasoid RA patients and 119
      ethnically matched controls. No significant differences in the allele frequencies
      of the three polymorphisms were found between controls and RA patients. In
      contrast, a significant association between the 1082*A allele and the (-1082*A/
      819*C/-592*C) haplotype and IgA RF+ve/IgG RF-ve patients was observed. The
      association of genotypes encoding low IL-10 production with IgA RF in RA is
      incompatible with its suggested role in antibody isotype switching. IgA RF has
      been associated with severe RA and may thus be indirectly correlated with a
      genotype encoding low IL-10 production.

PMID- 9572643
TI  - A 15-year exercise program for rheumatoid vasculitis.
AB  - A rare case of rheumatoid vasculitis and responses to a 15-year supervised
      exercise program. This patient presented with significant impairment in mobility
      and physical work capacity. His exercise tolerance improved considerably and he
      benefited emotionally.

PMID- 9572642
TI  - An association between the natural course of shoulder joint destruction in
      rheumatoid arthritis and HLA-DRB1*0405 in Japanese patients.
AB  - To assess the association between HLA-DRB1 alleles and shoulder destruction due
      to rheumatoid arthritis (RA) in Japanese, we typed for HLA-DRB1 alleles in 100
      Japanese RA patients who could be classified into 5 groups: non-progressive (N)
      with normal radiographs; erosive (E) showing marginal erosion but no collapse;
      collapse (C) showing subchondral cysts followed by collapse; arthrosis-like (A)
      showing osteoarthrotic features; and the mutilating (M) showing mutilating bone
      destruction. The HLA-DRB1*0405 antigen frequency in N, E, C, A, and M types was
      55%, 61%, 33%, 71%, 100%, respectively. That in the M type (100%) was
      significantly higher than that in the others (the N, E, C, and A types; 57%).
      These findings suggest that the most severe shoulder joint destruction pattern in
      RA, the M type, is associated with HLA-DRB1*0405.

PMID- 9572644
TI  - Perforation of the sigmoid colon in a rheumatoid arthritis patient treated with
      methylprednisolone pulses.
AB  - We describe a 61 year-old caucasian male diagnosed with rheumatoid arthritis. He
      was started on methylprednisolone pulses because of a severe flare of symmetric
      polyarthritis while he was on weekly intramuscular methotrexate and low-dose oral
      prednisone. After the second pulse of methylprednisolone the patient suddenly
      developed severe abdominal pain with free air under the right hemidiaphragm in
      the chest roentgenogram. The emergency surgery revealed the perforation of a
      colonic diverticulum. We suggest that methylprednisolone pulses should be
      carefully used in those patients over 50 years of age and/or people with
      demonstrated or suspected diverticular disease.

PMID- 9572645
TI  - Carotid tenderness: an ominous sign of giant cell arteritis?
AB  - Giant cell (temporal) arteritis is a systemic vasculitis involving medium and
      large-sized vessels. Despite the high frequency of involvement of cranial
      arteries, pain on examination of the external carotid artery itself has been
      exceptionally reported. We describe 3 patients with biopsy-proven giant cell
      arteritis (GCA) and wincing pain on palpation over the external carotid. The
      presence of this sign may be a harbinger of the existence of severe vascular
      involvement in patients with GCA.

PMID- 9572646
TI  - Effects of intravenous immunoglobulins on disease activity and cytokine plasma
      levels in rheumatoid arthritis.

PMID- 9572647
TI  - Difference in pharmacological activity between CPH 82 and podophyllotoxin.

PMID- 9572648
TI  - Strategies for improving the outcome of patients with poor prognosis prostate
      cancers.

PMID- 9572649
TI  - Mechanistic versus empirical explanations and evidence-based medicine.

PMID- 9572650
TI  - A comprehensive clinical epidemiological theory based on the concept of the
      source person-time and four distinct study stages.
AB  - The medical community is forced to accelerate the move from opinion-based to
      evidence-based medicine, that is, to aim at basing all caring and clinical
      practice on empiri. A clear-cut epistemology would facilitate this process. In
      this article we present a comprehensive clinical epidemiological theory which can
      be used for validity issues in caring science, quality of life research,
      controlled clinical trials and compilations of uncontrolled evidence. The theory
      is based on four distinct stages that can be identified in a study, whereof the
      first is demarcation of the source person-time. A source person-time ('study
      base') can be identified for any study in all disciplines, giving an argument for
      using this concept as the common reference point for validity issues. Apart from
      identifying the source person-time, recovery of the actually observed person
      time, collection of data and calculation of an ('adjusted') effect parameter
      (e.g., incidence ratio) are additional stages of a study. When the source person
      time is demarcated confounding is introduced, when the actually observed person
      time is recovered misrepresentation, in the third stage misclassification and in
      the fourth analytical alteration of the parameter of effect. The concept of the
      source person-time can, in addition, link examination of validity in caring and
      clinical sciences to observational studies, thereby allowing the field to benefit
      from all theoretical achievements for preventing, handling and understanding
      systematic errors developed in epidemiology. We conclude it is possible to
      implement a common terminology of validity for all caring and medical sciences.
      Drawing causal inferences in these disciplines is not mechanical, it can never,
      for example, be done with statistical inference. Establishing a causal relation
      always includes an assessment of the magnitude and direction of systematic errors
      influencing the adjusted effect parameter. From the presented epistemology it
      follows that differences in validity from a case history to a large randomized,
      placebo-controlled and double-blinded study are quantitative rather than
      qualitative. This realization in turn opens up for a more refined discussion of
      when a decision is evidence-based rather than opinion-based.

PMID- 9572651
TI  - The Swedish National Care Programme for Anal Carcinoma--implementation and
      overall results.
AB  - The Swedish National Care Programme for Anal Carcinoma (SNCPAC) was instituted in
      order to create a uniform handling policy for anal cancer and thus to accrue a
      population-based material allowing unbiased analyses. This study evaluates the
      degree of implementation of the SNCPAC guidelines, and presents overall treatment
      results in a total of 356 patients with epidermoid cancer of the anus and the
      perianal region diagnosed in Sweden between 1985 and 1989. Primary treatment
      according to the guidelines was irradiation up to 40 Gy, Bleomycin was
      administered intramuscularly before the first 18 fractions. After a 3-week pause,
      radiotherapy was to be continued up to a dose of 60-64 Gy, if at least an almost
      complete response was achieved. Otherwise, the patient was recommended surgery
      within a week. The guidelines were applied in 90%, of cases where such treatment
      was possible. The 5-year tumour-specific survival rate was 72%. The survival rate
      was more favourable in perianal tumours (90%) than in anal canal tumours (68%, p
      < 0.01). The 5-year probability of having a preserved anus was 64% (anal
      canal/perianal 58%/91%, p < 0.001). Bleomycin did not appear to have any effect
      on treatment results. The care programme has had a rapid and almost complete
      nation-wide penetration, and h as created the desired uniformity allowing proper
      analyses. The treatment results also appear comparable with specialised referral
      centres.

PMID- 9572652
TI  - Effects of fractionated irradiation on the cytoskeleton and basal lamina in
      parotid glands--an immunohistochemical study.
AB  - Cytoskeletal, cytocontractile and basement membrane proteins were studied using
      the immunofluorescence technique in the parotid gland in female rats after half
      side fractionated megavoltage irradiation. The non-irradiated parallel-handled
      parotid glands served as controls. The qualitative expression of cytoskeletal
      proteins remained unchanged 10 days following irradiation compared to controls,
      i.e. cytokeratin was observed but not vimentin, desmin or GFAP (glial fibrillary
      acidic proteins). Six months after irradiation the cytokeratin expression
      adjacent to duct lumina was clearly stronger. Actin staining was more pronounced
      in the periphery of the acini. Ten days after irradiation no alterations of the
      basal lamina proteins, laminin and fibronectin, were detected. Six months post
      irradiation laminin deposits were detected in areas where the entire acini had
      degenerated and had been replaced by fibrosis. An increased expression of
      fibronectin was also observed in the stroma at that time, reflecting an increased
      fibrosis. In areas where the acini remained, laminin immunofluorescence was
      mainly found in basal laminae of normal thickness, but the mean diameter of the
      acini seemed to have increased. This indicates a regeneration of acini and a
      restructuring of the basal lamina of the parenchyma.

PMID- 9572654
TI  - Relative survival of cancer patients--a comparison between Denmark and the other
      Nordic countries.
AB  - The results of a Nordic collaborative project revealed that Danish cancer
      patients had a poorer prognosis than patients in the other Nordic countries for
      some major cancer sites. The present study was undertaken to further explore the
      differences in survival between Denmark and the other Nordic countries. All
      cancer cases diagnosed in the Nordic countries during 1958 to 1991/92 were
      included in the analysis. Relative survival and excess mortality were calculated
      for intervals in the first five years after diagnosis. Since the 1950s, the
      prognosis of cancer patients has improved in all the countries, but more
      moderately in Denmark. For cancers of the stomach, colon, rectum, breast
      (female), and prostate, the Danish patients had a markedly lower relative
      survival than the patients in the other countries. They also had the lowest
      proportion of localized tumours. It appears that Danish cancer patients are
      diagnosed at a later stage of disease than patients in the other Nordic
      countries.

PMID- 9572653
TI  - Neoadjuvant chemotherapy for extremity osteosarcoma--preliminary results of the
      Rizzoli's 4th study.
AB  - A neoadjuvant chemotherapy protocol (1/93-1/95) for extremity osteosarcoma
      preoperatively using high-dose methotrexate (HDMTX) as single agent per cycle and
      three different combinations of other drugs (CDP/IFO,CDP/ADM,IFO/ADM) is
      reported. The four drugs were used postoperatively as single agents. Treatment
      was uniform, but suspended earlier if total necrosis was attained. An improvement
      was found in the results of the previous study using only IFO postoperatively,
      with 16/119 patients (97%) avoiding amputation, and 38 (32%) attaining complete
      necrosis. At a 3-year (2-4 years) mean follow-up, 92 patients (76%) remained
      continuously disease-free, 2 died of chemotherapy-related toxicity and 25
      suffered relapse. Projected 3-year DFS also improved (75% vs. 60%; p = 0.04).
      Despite limb salvage, local recurrences (6.3%) and infections were few, although
      postoperative chemotherapy was restarted within a week. Therefore, until new
      effective drugs are found, expertise in using the four known drugs may improve
      cure rate and help to avoid amputation in almost all patients.

PMID- 9572655
TI  - Analysis of postoperative vaginal vault radiotherapy of stage I endometrial
      cancer with different radionuclides.
AB  - A total of 213 patients in stage I grade 1 endometrial cancer were treated
      postoperatively with either radium or caesium vaginal applicators. The rate of
      complication and the incidence of second malignancies were studied in both
      groups. The frequency of grades 2 and 3 vaginal complications was higher among
      patients treated with caesium applicators but not statistically significant. The
      observed number of second malignancies was significantly higher than expected in
      the radium-treated group, in which the observed number of second malignancies
      with distant location was also significantly higher than expected, which could
      not be found in the caesium group.

PMID- 9572656
TI  - Colonic cell proliferation in normal mucosa of patients with colon cancer.
AB  - Cell kinetics parameters have been analysed in colonic mucosa at different
      distances from a tumour in patients with colon carcinoma. Total cell number
      (TCN), 3H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index
      (GCI) and the distribution of labelled cells along the crypt column (cell
      position frequency plot) were determined in well-aligned crypts. Total cell
      number, GCI and the labelled cell position frequency plots were similar in
      different samples from the same individual. A negative linear correlation between
      TCN and TLI was observed. The analysis of the cell position plots showed two
      patterns 1) with a high concentration in the bottom fifth of the crypt and 2)
      with frequent labelled cells at high positions. Whereas a negative correlation
      between overall TLI and the percent contribution to the TLI of the lowermost
      fifth was seen, the correlation was positive for the next 3 fifths and labelling
      was absent in the last part of the crypt.

PMID- 9572657
TI  - Low detection rate of HPV in oral and laryngeal carcinomas.
AB  - The presence of human papillomaviruses (HPVs) in 38 oral and 16 laryngeal lesions
      (verrucous hyperplasia, carcinoma in situ and carcinomas) was investigated using
      the polymerase chain reaction (PCR) technique. All biopsies were fresh frozen and
      a set of consensus and type-specific primers was used for PCR detection and HPV
      typing. In oral biopsies a low proportion of HPV-positive cases was found,
      despite the sensitive techniques. Only one case out of 38, a carcinoma in situ
      was positive (2.6%). It is thought that this finding reflects a minimal presence
      of HPV in the oral lesions, but a transient role of virus in the induction of
      carcinomas cannot be ruled out. Differences in relation to other studies may be
      geographical and/or methodological. In laryngeal carcinomas (and dysplasias), 3
      out of 16 cases were HPV positive. This frequency (19%) concurs with most other
      studies.

PMID- 9572658
TI  - Incidence, etiologic aspects and clinicopathologic features in intrahepatic
      cholangiocellular carcinoma--a study of 51 cases from a low-endemicity area.
AB  - A total of 51 cases (19 males and 32 females) of intrahepatic cholangiocellular
      carcinoma (CCC) from a low-endemicity area of primary liver cancer was analyzed
      during the periods from 1958 to 1979 and from 1984 to 1991. The mean annual age
      adjusted incidence rate was 0.44 for males and 0.56 for females per 100,000
      inhabitants. CCC was diagnosed before death in only 31%. There was a female
      predominance in patients over 70 years of age (p < 0.05). At presentation,
      malaise (85%), weight loss (73%) abdominal pain (50%) and hepatomegaly (80%) were
      common. The median survival time from diagnosis was 2 months. The mean age at the
      time of death was 72 years (range 41-92). At autopsy, cholelithiasis was found in
      61% (81% in patients older than 70 years) and cirrhosis in 30% of patients.
      Cholelithiasis was more common in CCC (p < 0.01) than in hepatocellular carcinoma
      cases with the same mean age. Not one case of inflammatory bowel disease was
      found. The gross appearance of the tumor was predominantly massive (49%) or
      multinodular (35%). The most common histological features were tubular pattern of
      growth (82%) and abundant fibrous stroma. Metastases were particularly associated
      with the lymph nodes (41%), skeleton (26%) and lungs (16%).

PMID- 9572659
TI  - Angiocytotoxic therapy in human non-small cell lung cancer cell lines--advantage
      of combined effects of TNP-470 and SN-38.
AB  - The combined effects of TNP-470, a promising antiangiogenic agent, and SN-38, a
      camptothecin derivative, were evaluated in four human cultured cell lines derived
      from non-small cell lung cancer (NSCLC). Cytotoxicity experiments were determined
      by using a tetrazolium salt (MTT) assay. The inhibitory effects of TNP-470 on
      cell proliferation were dose related and the 50% inhibitory concentrations on
      these cell lines were 47.3-139.8 microM. Evaluation of drug interactions with
      isobologram and the combination index values showed that sequential exposure to
      SN-38 followed by TNP-470 produced synergistic effects in the four cell lines
      tested. Our findings suggest that such an angiocytotoxic chemotherapy might be
      promising for the treatment of NSCLC.

PMID- 9572660
TI  - Increased urinary polyamine excretion in unselected cancer patients related to
      host factors.
AB  - Unselected patients with solid malignant tumours were investigated in order to
      determine whether they displayed elevated urinary excretion of polyamines; and if
      so, whether polyamine excretion in such patients predicts disease progression, or
      is secondary to host and systemic factors. Thirty-eight male and female patients
      with generalized solid, mainly gastrointestinal, malignant tumours were
      investigated. Ten male patients operated on for infrarenal aortic aneurysms and
      15 otherwise healthy male and female patients hospitalized for minor surgical
      procedures served as reference patients, representing individuals with and
      without metabolic stress. Urine samples were collected from all patients during
      24 h for measurement of both total and individual excretion of polyamines during
      three consecutive days. Polyamine excretion was not significantly increased in
      cancer patients when compared by analysis of variance among the three patient
      groups. However, polyamine excretion was significantly elevated in both cancer
      and stressed, non-cancer patients compared with patients without stress (p <
      0.05). A multivariate analysis indicated that plasma protein and albumin
      concentrations, abnormal liver function tests and liver metastasis predicted
      variation in polyamine excretion in cancer patients (p < 0.01), but this was
      unrelated to survival. Our results demonstrate that increased polyamine excretion
      in cancer patients is related more to host factors than to tumour growth itself.

PMID- 9572661
TI  - Radiation therapy alone for growth hormone-producing pituitary adenomas.
AB  - We present our experience in the treatment of growth hormone (GH)-producing
      pituitary adenomas using irradiation alone. Between 1983 and 1991, 21 patients
      suffering from GH-secreting pituitary adenomas were treated with radiotherapy
      alone. Two bilateral opposing coaxial fields were used in 10 patients and in the
      remaining 11 a third frontovertex field was added. Treatment was given in 1.8-2
      Gy daily fractions and total dose ranged between 45 and 54 Gy. Treatment was
      given using a cobalt unit. Four patients treated with somatostatin prior to and
      14 patients treated after the end of radiotherapy experienced symptom relief for
      6-28 weeks. The 5-year actuarial rate of disease control was 72%. Five out of six
      failed patients had macroadenomas. Hypopituitarism was observed in 5/21 (24%)
      patients. Whereas RT alone is effective in the treatment of microadenomas, this
      is not true for large infiltrative macroadenomas.

PMID- 9572662
TI  - High-dose radiation therapy alone for inoperable non-small cell lung cancer-
      experience with prolonged overall treatment times.
AB  - The purpose of this study as to determine the impact of overall treatment time on
      long-term survival after high-dose radiation therapy alone for inoperable non
      small cell lung cancer (NSCLC). Between 1978 and 1990, 229 patients with stage I
      III disease and Karnofsky Performance Scores of 80-100 received a conventionally
      fractionated total dose of 70 Gy through a split-course technique. After a first
      treatment course of 40 or 50 Gy, a restaging was performed and only patients
      without any contraindications, such as newly diagnosed distant metastases or
      serious deterioration of performance status, were given a second course. In 83%
      of patients this break lasted for 4-6 weeks. Overall treatment time ranged
      between 7 and 24 weeks (median 12 weeks). Median follow-up time was 6.6 years
      (range 4.0-9.3 years). Actuarial overall survival rates at 2 and 5 years were 28%
      and 7% respectively. Complete radiological tumor response was observed in 31% of
      patients, and was found to be the strongest positive predictor of survival with 2
      and 5-year rates of 50% and 12% respectively compared with 17% and 4% for
      patients without complete response. Treatment duration was not found to be a
      significant prognostic factor in univariate or multivariate analysis. For overall
      treatment times of 7-11 weeks (n = 50), 12 weeks (n = 79) and > 12 weeks (n =
      100), 5-year survival was 4%, 6%, and 8%, respectively (p = 0.6). To conclude, in
      our experience and in contrast to other studies, prolonged overall treatment
      times in radiation therapy alone for inoperable NSCLC had no negative impact on
      long-term survival. It is hypothesized that accelerated tumor cell repopulation
      is absent in a significant number of these patients with the time-factor playing
      no apparent role for outcome of treatment.

PMID- 9572663
TI  - Haemolytic uraemic syndrome associated with bleomycin, epirubicin and cisplatin
      chemotherapy--a case report and review of the literature.

PMID- 9572664
TI  - Cisplatin, methotrexate and mitoxantrone in patients with metastatic or advanced
      urothelial cancer.

PMID- 9572665
TI  - Guidelines for the use of antiretroviral agents in pediatric HIV infection.
      Center for Disease Control and Prevention.
AB  - Although the pathogenesis of human immunodeficiency virus (HIV) infection and the
      general virologic and immunologic principles underlying the use of antiretroviral
      therapy are similar for all HIV-infected persons, there are unique considerations
      needed for HIV-infected infants, children, and adolescents, including a)
      acquisition of infection through perinatal exposure for many infected children;
      b) in utero exposure to zidovudine (ZDV) and other antiretroviral medications in
      many perinatally infected children; c) differences in diagnostic evaluation in
      perinatal infection; d) differences in immunologic markers (e.g., CD4+ T
      lymphocyte count) in young children; e) changes in pharmacokinetic parameters
      with age caused by the continuing development and maturation of organ systems
      involved in drug metabolism and clearance; f) differences in the clinical and
      virologic manifestations of perinatal HIV infection secondary to the occurrence
      of primary infection in growing, immunologically immature persons; and g) special
      considerations associated with adherence to treatment for children and
      adolescents. This report addresses the pediatric-specific issues associated with
      antiretroviral treatment and provides guidelines to health-care providers caring
      for infected infants, children, and adolescents.

PMID- 9572667
TI  - Demographic characteristics of persons without a regular source of medical care-
      selected states, 1995.
AB  - Having a regular source of medical care (i.e., a regular provider or site) is one
      of the strongest predictors of access to health-care services, which has been
      associated with greater use of preventive health services. This report summarizes
      state-specific data from the 1995 Behavioral Risk Factor Surveillance System
      (BRFSS) and examines demographic factors associated with not having a regular
      source of medical care among adults in the 10 states for which this information
      was available. The findings indicate that certain demographic characteristics are
      associated with lack of a regular source of medical care.

PMID- 9572666
TI  - Measles--United States, 1997.
AB  - During 1997, a provisional total of 138 confirmed measles cases was reported to
      CDC by local and state health departments, the lowest number of measles cases
      ever reported in 1 year and a 55% decrease from the previous record low of 309
      cases reported in 1995. This report describes the epidemiology of measles in the
      United States in 1997, which suggests that no endemic measles virus is
      circulating in the United States.

PMID- 9572668
TI  - Update: influenza activity--United States and worldwide, 1997-98 season, and
      composition of the 1998-99 influenza vaccine.
AB  - In collaboration with the World Health Organization (WHO), the WHO international
      network of 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
      surveillance for influenza in the United States and worldwide during the 1997-98
      influenza season and describes the composition of the 1998-99 influenza vaccine.

PMID- 9572669
TI  - Nosocomial Ralstonia pickettii colonization associated with intrinsically
      contaminated saline solution--Los Angeles, California, 1998.
AB  - From February 24 through March 15, 1998, a total of 22 respiratory tract cultures
      from 13 patients at Childrens Hospital Los Angeles (CHLA), California, were
      culture-positive for Ralstonia pickettii. Because of this unusual cluster of
      colonization, on March 16 the Los Angeles County Department of Health Services
      initiated an investigation. This report summarizes the findings of the
      investigation, which resulted in a recall of sterile sodium chloride solution
      that was contaminated with R. pickettii.

PMID- 9572670
TI  - Expression of mRNAs for neurotrophins (NGF, BDNF, and NT-3) and their receptors
      (p75NGFR, trk, trkB, and trkC) in human peripheral neuropathies.
AB  - The steady-state mRNA levels of NGF, BDNF and NT-3, and the mRNA levels of their
      receptors p75NGFR, trk, trkB, and trkC were examined in various human peripheral
      neuropathies, to determine the correlation with myelinated fiber pathology and T
      cell and macrophage invasions in the diseased nerves. Steady state levels of
      p75NGFR mRNAs were significantly elevated in nerves with axonal pathology. In
      contrast, steady state levels of trkB and trkC mRNA levels were diminished. trk
      mRNA was not detected in the human nerves. The NGF, BDNF, and NT-3 mRNA levels
      were elevated in the diseased nerves. The increase in BDNF and NT-3 mRNA levels
      were proportional to the extent of invasion of the nerves by T cells and
      macrophages, but did not directly correlate with axonal nor demyelinating
      pathology, thus suggesting that inflammatory cell invasions are involved in the
      regulation of BDNF and NT-3 mRNA expressions. These neurotrophin and their
      receptor gene expressions in the diseased human nerves would be regulated by an
      underlying pathology-related process, and could play a role in peripheral nerve
      repair.

PMID- 9572671
TI  - Effects of arginine vasopressin and atriopeptin on chloride uptake in cultured
      astroglia.
AB  - Ion and water homeostasis in the CNS is subjected to a neuroendocrine control
      exerted by neuropeptides formed within the brain. In order to gain information on
      this neuroendocrine control of Cl- homeostasis, 36Cl- uptake was measured in
      cultured Type-I astrocytes exposed to the neuropeptides [Arg8]Vasopressin (AVP),
      and atriopeptin (AP) and to various Cl- transport modifiers. AVP increased while
      AP decreased 36Cl- uptake of cultured astrocytes in a dose-dependent manner. Both
      effects became statistically significant at greater than 10(-9) M concentration
      of the peptides. For the appearance of the effects at least 30-min exposure was
      necessary. AVP and AP extinguished each other's effect by almost stochiometric
      manner. When administered together with AVP, the VIA vasopressin receptor
      antagonist "Manning compound" inhibited, while V2 vasopressin receptor agonist
      did not influence the 36Cl- uptake-increasing effect of AVP. However, bumetanide,
      a specific inhibitor of Na+-K+-2Cl- cotransport, inhibited the effect of
      vasopressin and also inhibited the 36Cl- uptake of AVP non-treated, control
      cells. Our findings suggest that brain Cl- homeostasis is controlled by
      neuroendocrine system in the CNS.

PMID- 9572672
TI  - Relationship between 2,5-hexanedione concentrations in nerve, serum, and urine
      alone or under co-treatment with different doses of methyl ethyl ketone, acetone,
      and toluene.
AB  - To ascertain the relationship among 2,5-hexanedione (2,5-HD) concentrations in
      nerve, serum and urine, rats were injected subcutaneously with 2.6 mmol/kg 2,5-HD
      alone, or together with 2.6 or 13.0 mmol/kg of methyl ethyl ketone, acetone and
      toluene. 2,5-HD concentrations in sciatic nerve (NC), serum (SC) and urine (UC)
      were determined, and the linear regression between each two of NC, SC, and UC
      were calculated. There was good correlation between NC and SC, SC and UC in the
      2,5-HD alone group, and good correlation between NC and SC in the co-treated
      groups. Co-treatment solvent had little effect on the relationship between SC and
      NC. 13.0 mmol/kg co-treated solvent tended to decrease the regression
      coefficients compared with 2.6 mmol/kg co-treated solvent. These results show
      that SC can be used in estimating NC in the 2,5-HD alone or co-treated groups,
      and UC can be used in estimating SC in the 2,5-HD alone group.

PMID- 9572673
TI  - Histochemical, immunohistochemical, and electron microscopy study of the caudal
      portion of the chicken intestinal nerve of Remak.
AB  - In order to deepen our knowledge of the different components of the chicken
      intestinal nerve of Remak (I.N.R.), we have studied it by means of histochemical,
      immunohistochemical and electron microscopy techniques to distinguish the
      different neurotransmitters. We have found cholinergic cell bodies, as well as
      acetylcholinesterase (AChE) positive neuronal fibers, forming part of the web
      that constitutes the I.N.R. in its caudal portion, with a higher density of
      neuronal bodies in the ganglia. We also observed catecholaminergic neuronal
      bodies and fibers, located fundamentally in the periphery of the nerve, and a low
      density of catecholaminergic cell bodies. With respect to the vasoactive
      intestinal peptide (VIP) and substance P (SP) positive peptidergic innervation,
      we found more abundant neuronal bodies positive for the V.I.P. than for S.P.
      Electron microscopy corroborated the results observed under the optic microscope,
      showing the various types of vesicles containing different neurotransmitters.

PMID- 9572674
TI  - Differential inhibition by hyperammonemia of the electron transport chain enzymes
      in synaptosomes and non-synaptic mitochondria in ornithine transcarbamylase
      deficient spf-mice: restoration by acetyl-L-carnitine.
AB  - Sparse-fur (spf) mouse is the ideal animal model to study the neuropathology of
      congenital ornithine transcarbamylase (OTC) deficiency. Our current hypothesis
      implies that an ammonia-induced depletion of energy metabolism in the spf mouse,
      could be due to a reduction in the activities of the enzymes of the electron
      transport chain and a treatment with acetyl-L-carnitine could normalize this
      abnormality. We also hypothesized that there might be a differential degree of
      inhibition in synaptosomal and non-synaptic mitochondria, for the enzymes of the
      electron transport chain, caused by congenital hyperammonemia. We have therefore
      measured the activities of NADH-cytochrome C oxidoreductase, succinate cytochrome
      C oxidoreductase and cytochrome C oxidase in synaptosomes and non-synaptic
      mitochondria, isolated from spf mice and CD-1 controls with and without acetyl-L
      carnitine treatment. Our results indicate a significant reduction (19-34%) in the
      activities of these complexes in synaptosomes in untreated spf mice, whereas in
      non-synaptic mitochondria, there was a tendency for the activities to decrease.
      Acetyl-L-carnitine treatment enhanced these activities (15-64%) for all the three
      enzyme complexes and its effect was more prominent on succinate cytochrome C
      oxidoreductase activity (64%). These studies point out that: (a) ammonia-induced
      disturbances in the energy metabolism could be more pronounced in neuronal
      mitochondria, and (b) the effect of acetyl-L-carnitine on the restoration of
      cerebral ATP in hyperammonemia could be through an enhancement of the activities
      of various electron transport chain enzymes.

PMID- 9572675
TI  - Platelet MAO-B activity and serotonin content in patients with dementia: effect
      of age, medication, and disease.
AB  - This study aimed at determining the effect of drug therapy, age and type of
      dementia on biological markers. Both platelet monoamine oxidase type B (MAO-B)
      activity and serotonin content of 57 demented patients and 20 control subjects
      were determined. Platelet MAO-B activity was measured using [14C]tyramine as
      substrate. Serotonin content was determined by HPLC-EC method. Increased platelet
      serotonin content and platelet count was found in patients with dementia compared
      to controls. A positive correlation was experienced between platelet MAO-B
      activity, platelet serotonin content and age. Platelet MAO-B activity was higher
      in the haloperidol treated group, compared with patients treated with
      anxyolitics. The main original finding of the present study is that platelet
      serotonin content is increased in demented patients with delusions compared to
      dementia without complications (p = 0.006). It seems, that platelet MAO-B
      activity is influenced mainly by drug therapy, while serotonin content rather
      reflects clinical characteristics in dementia.

PMID- 9572676
TI  - Ammonia and manganese increase arginine uptake in cultured astrocytes.
AB  - Recent work has suggested a possible role for nitric oxide (NO) in the
      development of hepatic encephalopathy (HE). In this study, we examined the effect
      of ammonia and manganese, factors implicated in the pathogenesis of HE, on the
      transport of arginine (a precursor of NO) into primary cultures of astrocytes.
      Treatment with 5 mM ammonia for 1-4 days produced a maximal (53%) increase in L
      arginine uptake at 3 days when compared to untreated cells. Kinetic analysis
      following 4-day treatment with 5 mM ammonia revealed an 82% increase in the Vmax
      and a 61% increase in the Km value. Similar analysis with 100 microM manganese
      showed a 101% increase in Vmax and a 131% increase in the Km value. These results
      suggest that both manganese and ammonia alter L-arginine uptake by modifying the
      transporter for arginine. A decrease of 32% in the non-saturable component of L
      arginine transport was also observed following treatment with ammonia. When
      cultures were treated separately with 5 mM ammonia and 100 microM manganese for 2
      days, the uptake of L-arginine increased by 41% and 57%, respectively. Combined
      exposure led to no further increase in uptake. Our results suggest that ammonia
      and manganese may contribute to the pathogenesis of HE by influencing arginine
      transport and thus possibly NO synthesis in astrocytes.

PMID- 9572678
TI  - Chronic lithium treatment decreases brain phospholipase A2 activity.
AB  - Chronic lithium administration decreases the turnover of arachidonic acid (AA) in
      several brain phospholipids. This suggests that lithium may attenuate
      phospholipase A2 (PLA2) activity in brain. We now report effects of chronic
      lithium treatment on PLA2 activity in postnuclear supernatant from rat brain:
      Enzyme activity was determined by two assay methods, radiometric and
      fluorometric, and measured the release of the fatty acid on the second acyl
      position (sn2) from choline and ethanolamine phospholipids. PLA2 activity in
      brain postnuclear supernatant from rats chronically treated with lithium in the
      diet was significantly decreased (20-50%) when compared with controls. In vehicle
      or lithium-treated rats, PLA2 activity was not significantly augmented or
      attenuated by the addition of calcium chelators, divalent cations or LiCl
      supplementation (1.0 mM) to postnuclear supernatant. These results suggest that a
      major therapeutic effect of lithium is to attenuate brain PLA2 activity involved
      in signal transduction.

PMID- 9572677
TI  - Different effects of opiate withdrawal on dopamine turnover, uptake, and release
      in the striatum and nucleus accumbens.
AB  - The purpose of these experiments was to further characterize changes in
      dopaminergic function that follow withdrawal from chronic opiate treatment.
      Withdrawal after treatment to a maximum dose of 120 mg/kg of morphine did not
      alter dopamine concentrations in the substantia nigra, ventral tegmental area,
      striatum, or nucleus accumbens; but did decrease concentrations of DOPAC and the
      ratio of DOPAC to dopamine in the lateral striatum and nucleus accumbens. Uptake
      of tritiated dopamine was diminished for withdrawn slices obtained from the
      striatum with no effect observed for tissue from the nucleus accumbens. Deficits
      of in vitro release of tritiated dopamine also occurred following withdrawal,
      with the nucleus accumbens being sensitive to dependence produced by a lower dose
      of morphine. In conclusion, opiate withdrawal produces a complex pattern of
      effects on dopaminergic function that is specific for the striatum and nucleus
      accumbens.

PMID- 9572679
TI  - Enzymatic release of Zn2+-glycerophosphocholine cholinephosphodiesterase from
      brain membranes by glycosylphosphatidylinositol-specific phospholipases and its
      regulation.
AB  - Enzymatic conversion of glycosylphosphatidylinositol (GPI)-linked Zn2+
      glycerophosphocholine phosphodiesterase was investigated. The activity of
      glycosylphosphatidylinositol-specific phospholipase-D (GPI-PLD), based on the
      conversion of amphiphilic form of phosphodiesterase into hydrophilic form,
      showing an optimum pH of about pH 6.6, increased continuously until 60 min. The
      activity of membrane-bound GPI-PL, based on the formation of hydrophilic form of
      phosphodiesterase, exhibiting an optimum pH of 7.4, increased up to 30 min, and
      reached a plateau. Inhibition studies indicate that while GPI-PLD activity was
      generally sensitive to ionic bio-detergents, it was not inhibited by myristoyl
      glycerol, a neutral detergent. Meanwhile, the membrane-bound GPI-PL was not
      affected remarkably by these detergents except that myristoyl glycerol expressed
      a modest increase of activity of membrane bound GPI-PL. In addition, the membrane
      bound GPI-PL appeared to be enhanced by by suramin or oleic acid, which strongly
      inhibited GPI-PLD. From this results, it is suggested that in brain there may be
      two phospholipases responsible for the conversion of membrane-bound GPI-anchors
      to hydrophilic forms, and that this conversion might be regulated by endogenous
      lipids.

PMID- 9572680
TI  - Mycobacterium leprae binds to a 25-kDa phosphorylated glycoprotein of human
      peripheral nerve.
AB  - Mycobacterium leprae, the causative agent of leprosy, specifically invades and
      destroys the peripheral nerve, which results in the main clinical manifestation
      of the disease. Little is known about the bacteria-nerve protein interaction. We
      show in the present work that M leprae binds to a 25 kDa glycoprotein from human
      peripheral nerve. This protein is phosphorylatable and it binds to lectins which
      have alpha-mannose specificity. This M leprae-protein interaction could be of
      importance in the pathogenesis of leprosy.

PMID- 9572682
TI  - Effect of interstitial and/or systemic delivery of tirapazamine on the
      radiosensitivity of human glioblastoma multiforme in nude mice.
AB  - The purpose of this study was to investigate the feasibility and the efficacy of
      administering tirapazamine by a slow-releasing polymer disc that was implanted
      interstitially into a U251 (human glioblastoma multiforme) tumor grown in nude
      mice. Tumor-bearing animals, with a tumor nodule 0.8 cm3 in size, were
      distributed to groups receiving combinations of empty or drug-containing polymer
      implants in the tumor or contralateral leg, intraperitoneal (i.p.) drug, and/or
      irradiation. The drug (i.p.) alone (14 mg/kg x6) or in combination with tumor
      drug implant (2 mg) did not significantly increase the tumor volume doubling time
      compared to that of control animals. Given with 12 Gy of irradiation in twice a
      day 2-Gy fractions, combined i.p. drug and tumor drug implant significantly
      delayed tumor growth compared to irradiation alone, which was not achieved with
      either drug treatment alone added to irradiation. Toxicity, as manifested by
      transient weight loss, was primarily seen in animals receiving radiation and i.p.
      tirapazamine. These results indicated that a slow-releasing tirapazamine disc can
      be produced and the addition of an interstitially implanted tirapazamine disc
      further increased the effectiveness of i.p. tirapazamine.

PMID- 9572681
TI  - Elevated nerve growth factor levels in the synovial fluid of patients with
      inflammatory joint disease.
AB  - A novel pH shock extraction procedure was used to measure nerve growth factor
      (NGF) levels in both normal and inflamed synovial fluids using a sensitive and
      specific two-site enzyme linked immunosorbant assay. To date no data is available
      on NGF levels in normal synovial fluids. Synovial fluids were taken from 5 normal
      volunteers, 12 patients with rheumatoid arthritis and 10 patients with other
      inflammatory arthropathies. The mean +/- SEM NGF concentration in normal synovial
      fluids was 95 +/- 33.2 pg/ml (range 39.1-143.1 pg/ml), whereas the mean NGF
      concentration in the synovial fluids taken from patients with rheumatoid
      arthritis was 532.5 +/- 123.8 pg/ml (range 152-1686 pg/ml). The mean NGF
      concentration in patients with other inflammatory arthropathies was also raised
      (430.6 +/- 90 pg/ml; range 89-1071 pg/ml). The NGF concentrations were
      significantly higher in the synovial fluids from both inflamed groups (ANOVA p <
      0.05) compared to normals. Raised levels of NGF in synovial fluid may contribute
      directly to joint inflammation via activation of inflammatory cells.

PMID- 9572683
TI  - Optimal scheduling of interleukin-12 and fractionated radiation therapy in the
      murine Lewis lung carcinoma.
AB  - Interleukin-12 (IL-12), a naturally occurring cytokine, has demonstrated
      antitumor activity in several murine solid tumors. The Lewis lung carcinoma was
      used to study the most effective scheduling of recombinant murine interleukin-12
      (rmIL-12) administration with fractionated radiation therapy. The effect of the
      schedule of rmIL-12 administration alone or along with a 1- or 2-week
      fractionated radiation therapy regimen was examined. Beginning rmIL-12 prior to
      or at the same time as radiation therapy and extending rmIL-12 through the
      radiation regimen and beyond produced the longest tumor growth delays. Those
      treatment regimens which were most effective against the primary tumor were also
      most effective in decreasing the number of lung metastases on day 20. To further
      assess the immunotherapeutic effects from rmIL-12 administration, the efficacy of
      rmIL-12 with fractionated radiation therapy delivered to a right hind-limb tumor
      was measured as tumor growth delay in an unirradiated left hind-limb tumor. There
      was some difference in the tumor growth delay between the unirradiated tumor in
      the animals bearing an irradiated tumor in the contralateral leg, and the tumors
      in animals receiving rmIL-12 only. Recombinant murine granulocyte-macrophage
      colony stimulating factor (rmGM-CSF) was also an antitumor agent active against
      the Lewis lung carcinoma and produced an additive effect in combination with
      fractionated radiation therapy in this tumor. rmIL-12 was a radiation sensitizer
      in the Lewis lung carcinoma. When rmIL-12 (45-microg/kg) and rmGM-CSF (45
      microg/kg) were administered together with fractionated radiation therapy, a
      marked increase in tumor growth delay resulted. This treatment combination also
      nearly ablated lung metastases on day 20 in these animals. These results may
      serve as a useful guide in developing clinical protocols, including rmIL-12 and
      fractionated radiation therapy.

PMID- 9572684
TI  - Radiation therapy and breast reconstruction.
AB  - Mastectomy will continue to play a substantial role in the treatment of breast
      cancer, because many women either are not candidates for or do not desire to have
      breast conservation. Many patients treated with mastectomy will desire
      reconstruction, and many of these will be advised to receive adjuvant
      radiotherapy, which has been shown to increase overall survival in certain high
      risk patients. There continues to be considerable controversy regarding the
      compatibility of radiation therapy and breast reconstruction due to increased
      complications and decreased cosmetic outcome. These can be minimized by careful
      modern surgical and radiation techniques, and in most cases the result is
      acceptable, including for reconstructions with prosthetic implants as well as
      autogenous myocutaneous flaps.

PMID- 9572685
TI  - Comparison of MRI- and CT-based post-implant dosimetric analysis of transperineal
      interstitial permanent prostate brachytherapy.
AB  - The purpose of this work was to investigate how a recently developed MRI-based
      post-implant dosimetric analysis technique for ultrasound guided transperineal
      interstitial permanent prostate brachytherapy (TIPPB) compared with the currently
      accepted CT-based technique. The study was based upon 3-mm MRI and CT scans of 15
      patients who had received either 125I or 103Pd implantation. All images were
      acquired on post-operative day 1 and within 1 hr of each other. Prostate volumes
      were determined by the same physician. Sources were digitized and calculations
      performed using an in-house treatment planning system with a nearest neighbor
      seed sorting routine and AAPM TG43 formalism. Prostate volume, geometric source
      distribution spread (rcom), dose volume histogram (DVH), and tumor control
      probability (TCP) calculations were performed from both image sets. Differences
      in source localization were evaluated by comparing source spread and prescription
      isodose volumes. Differences in dosimetric analysis were evaluated through
      prostate-specific DVH and TCP comparisons. Prostate volume as determined from MRI
      was larger than that of CT by an average of +9.1% (R = 0.70). Calculated rcom was
      smaller by an average of -0.9 mm (R = 0.81). Isodose volumes at 80, 90, 100, and
      150% of the prescription dose differed by an average of +2.5, +2.9, -2.9, and
      +4.8%, respectively (R = 0.97, 0.98, 0.98, and 0.91). Percentage volume of the
      prostate encompassed by 80, 100, and 150% of the prescription dose differed by an
      average of -0.9, -0.9, and -0.1%, respectively (R = 0.34, 0.35, and 0.35). TCP
      differed by an average of -0.8% (R = 0.37). The results of this study further
      support our initial findings that MRI may be used to reliably localize the
      implanted sources for TIPPB. This study also demonstrated that MRI-based post
      implant dosimetric analysis is possible. However, it is evident that differences
      in prostate localization from MRI to CT can result in significantly different
      assessments of prostate volume coverage. There is clearly a need to further
      quantify the differences between these two imaging modalities in this application
      and address whether greater accuracy in describing the dose-volume relationship
      based on improvements in visualization of the prostate gland from MRI will
      translate into improved correlation with treatment outcome.

PMID- 9572686
TI  - Consolidative 32P after second-look laparotomy for ovarian carcinoma.
AB  - We report our experience with consolidative 32P after second-look laparotomy.
      Forty-three patients received consolidative 32P after platinum-based chemotherapy
      and a negative (39 patients, 91%) or positive (4 patients) second-look
      laparotomy. Thirty-one patients (72%) initially had stage III (30 patients) or
      stage IV (1 patient) disease; 28 patients (65%) had grade 3 tumors. Patients had
      follow-up from 3.5 to 14.9 years (median, 7.7 years); no patient was lost to
      follow-up. The 5-year rates of control of disease within the abdomen (local
      control) for the overall group and the subset of patients with stage II-IV
      disease and a negative second-look laparotomy were 65% and 69%, respectively. The
      corresponding 5-year survival rates were 78 and 81%, respectively. Multivariate
      analyses revealed that tumor found at second-look laparotomy significantly
      influenced the likelihood of local control and cause-specific survival. Acute
      side effects included cellulitis (1 patient) and ileus (3 patients). Two patients
      (5%) experienced severe late complications; both experienced small bowel
      obstruction that necessitated surgical intervention. Consolidative 32P appears to
      reduce the risk of recurrence and improve survival after negative second-look
      laparotomy. The risk of significant complications is low.

PMID- 9572687
TI  - The fate of 10-year clinically recurrence-free survivors after definitive
      radiotherapy for T1-3N0M0 prostate cancer.
AB  - We recently reported the outcome of 168 patients treated with pelvic
      lymphadenectomy and definitive radiation therapy. This report is a subanalysis of
      those patients (pts) who were clinically without evidence of disease (NED) 10
      years after a negative staging pelvic lymphadenectomy and definitive radiation
      therapy for prostate cancer. One hundred of our original cohort of 168 patients
      had at least ten year follow-up. 76 patients had pathologically negative lymph
      nodes and had not received hormonal therapy. Forty-two N0 patients with
      sufficient follow-up were alive and clinically NED 10 years post-operatively.
      Distribution by disease stage at diagnosis was: Stage A2: 12 pts; Stage B: 19
      pts; Stage B2/C: 6 pts; Stage C: 5 pts. Median follow-up was 13.3 years, with a
      minimum follow-up of 10 years. Of the 42 patients clinically NED at 10 years, 5
      pts died subsequently without PSA data, remaining clinically NED a median of 13 y
      3 m postoperatively; 37 patients were alive and without evidence of disease off
      all therapy at 10 years post-operatively. Bone scans were performed on 8 of the 9
      patients with PSA over 4.0 ng/ml or on hormonal therapy. These revealed a single
      patient with diffuse but asymptomatic bone metastases. Ultrasound-guided sextant
      biopsies were performed on one 78-year-old patient with elevated PSA 19 years
      post-operatively, revealing an asymptomatic local recurrence. Patients who
      survive clinically NED for 10 years have a low likelihood of clinical failure,
      even in the presence of PSA values between 4.0 and 10 ng/ml. In these patients,
      PSA trends are of greater utility than absolute values.

PMID- 9572688
TI  - Human papillomavirus is present in some cases of childhood penile lichen
      sclerosus: an in situ hybridization and SP-PCR study.
AB  - Lichen sclerosus (LS) is a skin disease that may affect both sexes at all ages
      and at any site. Its etiology remains unknown. The observation of focal
      koilocytotic-like changes in the stratum malpighii in prepuce samples of LS in
      children prompted us to investigate the presence of HPV-DNA. Twenty-three
      paraffin-embedded samples of LS lesions from children aged 4 to 14 years were
      studied using nested-PCR and in situ hybridization (ISH). Twelve out of 23 cases
      amplified HPV-DNA (8 cases corresponded to HPV-DNA type 6; 2 cases each to HPV
      DNA types 16 and 18). ISH detected HPV sequences in the nuclei of koilocytotic
      and some parakeratotic cells in 13 cases (9/13 also HPV-DNA positive by PCR). Our
      results demonstrated the presence of HPV-DNA in roughly 70% of cases of LS of the
      prepuce in children. We highlight the observation of koilocytotic-like changes in
      the prepuce and its association with HPV. The possible pathogenetic significance
      between the virus and the lesion is not settled.

PMID- 9572689
TI  - Acute hemorrhagic edema of childhood (AHE)
AB  - Four patients with acute hemorrhagic edema (AHE) of childhood are presented. Two
      patients had associated pulmonary tuberculosis. AHE of childhood is a benign
      condition, characterized by inflammatory edema and ecchymotic purpura in a target
      or cockade pattern. Histology of the skin lesions shows typical leucocytoclastic
      vasculitis and the condition has therefore been considered a variant of Henoch
      Schonlein purpura (HSP). However, because of its benign course, AHE should be
      considered as a separate entity.

PMID- 9572690
TI  - Palmoplantar eccrine hidradenitis: three new cases and review.
AB  - Palmoplantar eccrine hidradenitis (PEH) is characterized by painful erythematous
      papules and nodules of abrupt onset on the soles of young individuals. The
      histologic hallmark is a predominant neutrophilic infiltrate surrounding the
      eccrine gland apparatus. A total of 28 cases have been published since 1988, with
      a broad variation in the age of patients, symptomatology, associated diseases,
      clinical course, and histologic features. These different histologic pictures
      have resulted in several names for this entity, including idiopathic plantar
      hidradenitis, neutrophilic eccrine hidradenitis, recurrent palmoplantar
      hidradenitis in children, and idiopathic palmoplantar hidradenitis. We present
      three cases of this disorder and review the literature on the varying
      symptomatology, clinical course, and histology that have led to the myriad of
      names for this disease.

PMID- 9572691
TI  - Cutaneous polyarteritis nodosa in a child.
AB  - Cutaneous polyarteritis nodosa (CPAN) is a benign form of vasculitis of small and
      medium-size arteries with a recurrent but benign course without systemic
      involvement. This entity is very rare in children, with about 45 cases described
      in the literature we reviewed. Herein we report a 10-year-old girl with typical
      CPAN. Trigger factors such as streptococcal infection were not detected. Of four
      episodes over the last 2 years, only one required treatment with a moderate-sized
      oral dose of prednisone. In diagnosing CPAN, it is necessary to rule out systemic
      polyarteritis nodosa, which is also rare in children, as well as other
      panniculitides and vasculitides.

PMID- 9572692
TI  - Bullous pemphigoid in infancy: case report and literature review.
AB  - We report a 2-month-old girl who developed bullous pemphigoid on her hands and
      feet shortly after receiving her routine immunizations. Infantile bullous
      pemphigoid has a clinical presentation distinct from bullous pemphigoid seen in
      older children and should be included in the differential diagnosis of blisters
      involving the hands and feet. Our patient responded well to topical
      corticosteroid therapy.

PMID- 9572693
TI  - Coexistence of incontinentia pigmenti and neonatal herpes simplex virus
      infection.
AB  - We present a female infant with classic clinical and histologic features of stage
      I incontinentia pigmenti with coexistent neonatal herpes simplex virus infection.
      The diagnosis of a heritable cutaneous condition does not exclude the possibility
      of a coexistent infection and, given the similar clinical presentation of
      neonatal vesicular eruptions, accurate diagnoses may require skin biopsy and
      culture.

PMID- 9572694
TI  - Cutaneous myiasis caused by Dermatobia hominis.
AB  - We report a case of myiasis caused by larvae of Dermatobia hominis in a 12-year
      old boy. The infestation was acquired in Uruguay and was characterized by a
      single, large, inflammatory, nodular lesion located on the scalp. The lesion was
      accompanied by local pruritus and pain as well as diffuse headache and regional
      lymphadenopathy. From the lesion a single larva in stage III, of noteworthy size,
      was removed. Very few pediatric cases of myiasis due to D. hominis have been
      reported in the literature. Furthermore, as far as we know, just one adult case
      of myiasis caused by D. hominis acquired in Uruguay has been published.

PMID- 9572695
TI  - Cervicofacial hemangioma and a minor sternal malformation: inclusion in PHACES
      syndrome?
AB  - Hemangiomas are frequent in childhood, but those associated to dysmorphic
      anomalies are rare. We report a young girl with hemangiomas of the face, neck,
      and upper trunk, severe laryngeal dyspnea, and sternal atrophic skin without
      sternal nonunion, probably corresponding to a minor form of PHACES syndrome.

PMID- 9572696
TI  - Fatal Pseudomonas septicemia and vasculitis in a premature infant.
AB  - A characteristic vasculitis is an uncommon but well-recognized complication of
      severe Pseudomonas aeruginosa infection in the neonate. Although it is one of the
      most common gram-negative organisms responsible for overall nosocomial infection,
      it is a rare cause of intrauterine or intrapartum infection of the newborn. We
      describe a fatal Pseudomonas aeruginosa infection occurring in a very premature
      infant with widespread skin necrosis. Although this organism is relatively
      uncommon in the neonate, premature infants are at increased risk of infection,
      with a significant associated mortality. Early recognition and treatment are
      therefore very important.

PMID- 9572697
TI  - An intriguing case of LEOPARD syndrome.
AB  - We report a 9-year-old boy affected by LEOPARD syndrome, who also had ichthyosis,
      axillary freckling, two cafe au lait spots, and one neurofibroma. The diagnosis
      of LEOPARD syndrome has been made on clinical grounds, whereas the ichthyosis and
      neurofibroma have been histologically confirmed. The analogies between LEOPARD
      syndrome and neurofibromatosis have been discussed. Finally, we maintain this
      case is an example of the multiple lentigines syndrome/LEOPARD syndrome spectrum.

PMID- 9572698
TI  - A double-blind, randomized, placebo-controlled trial of eutectic
      lidocaine/prilocaine cream 5% (EMLA) for analgesia prior to cryotherapy of warts
      in children and adults.
AB  - Liquid nitrogen cryotherapy is an effective treatment modality for verrucae in
      children. However, sometimes the pain of the procedure is too much for the young
      child. In such instances the availability of an effective topical anesthetic
      would be of tremendous benefit. Warts are usually present on hardened skin, that
      is, the palms, periungual areas, and soles. In a double-blind, randomized,
      placebo-controlled, single-center, parallel-group trial with one visit, children
      (6-18 years old) and adults (>18 years old) had 2.5 g of lidocaine/prilocaine
      cream 5% applied under an occlusive dressing to the wart and a 1 to 2 mm area
      surrounding it 1 hour prior to liquid nitrogen cryotherapy. In both age groups
      the warts were subdivided by location-hardened skin areas versus nonhardened skin
      sites. The topical anesthetic was then removed and cryotherapy applied for 5 to
      10 seconds. The pain of cryotherapy was assessed by the patient on a visual
      analogue scale (VAS) immediately after the cryotherapy and 4 and 8 hours later.
      There was no statistically significant difference in the pain of cryotherapy
      experienced following the application of active cream (n = 64) and placebo (n =
      64). Exploratory subgroup analysis by wart location showed promising results for
      lidocaine/prilocaine cream 5% over placebo in children with warts on hardened
      skin sites (palms and soles). The topical anesthetic was safe and generally well
      tolerated. Lidocaine/prilocaine cream 5% may provide some anesthesia in children
      receiving cryotherapy when the wart is on the palms or soles. Further studies are
      needed to better understand the site and age specificity of the anesthetic
      properties of lidocaine/prilocaine cream 5% when used to reduce the pain
      experienced during cryotherapy of warts.

PMID- 9572699
TI  - Cleansers, moisturizers, and talcs: patterns of use among children of low
      socioeconomic level.
AB  - The use of cosmetics (cleansers, moisturizers, and talcs) was investigated in 200
      infants and children of low socioeconomic level with and without skin disease.
      For children with atopic dermatitis, mothers preferred to use unscented soap.
      Lubricating or hydrating creams were widely used in children without skin
      disease. Talc and mineral oil were significantly more frequently used in infants
      than in children. Both of these products are potentially harmful and represent an
      unnecessary expense for families with a survival-level budget. Dermatologists
      should discourage their use.

PMID- 9572700
TI  - What syndrome is this? Menkes' kinky-hair syndrome.

PMID- 9572701
TI  - Keratotic papules on the palm of a 12-year-old boy.

PMID- 9572702
TI  - Pulmonary hemorrhage associated with Henoch-Schonlein purpura.

PMID- 9572703
TI  - Infantile perianal pyramidal protrusion: a marker of constipation?

PMID- 9572704
TI  - Identical twins with perioral dermatitis.

PMID- 9572705
TI  - Evaluation of the effectiveness of childhood generalized pustular psoriasis
      treatment in 30 cases.

PMID- 9572707
TI  - Proceedings of the 1997 meeting of the Society for Pediatric Dermatology.

PMID- 9572706
TI  - Lymphomatoid papulosis in childhood with exclusive acral involvement.

PMID- 9572708
TI  - Autoantibodies and common viral illnesses.
AB  - OBJECTIVES: To review the literature about common autoantibodies produced in
      association with viral infection. METHODS: Medline review of the medical
      literature published in English. RESULTS: Common viral infections are often
      associated with low-titer, polyspecific autoantibodies. However, high-titer
      antinuclear antibodies, double-stranded DNA antibodies, anticardiolipin
      antibodies, and other subtype antibodies may be found. Hepatitis C and B virus,
      human immunodeficiency virus, and parvovirus B19 appear to be associated with
      autoantibodies more commonly than other viruses. CONCLUSIONS: Transient
      autoantibodies resulting from viral infections are not uncommon. Clinical and
      laboratory follow-up over time will help distinguish between connective tissue
      disease and self-limited illness.

PMID- 9572709
TI  - Posterior tibial neuropathy from ruptured Baker's cyst.
AB  - OBJECTIVES: To increase awareness of entrapment neuropathy caused by rupture of
      Baker's cyst. METHODS: A patient with psoriatic arthritis, ruptured Baker's cyst,
      and entrapment neuropathy is reported and the literature on this complication is
      reviewed. RESULTS: Nerve entrapment caused by rupture of Baker's cyst is rare.
      Neurological examination and demonstration of Baker's cyst by Color Doppler
      Duplex Ultrasound (CDDU) help in making the diagnosis. Nerve Conduction Study
      (NCS) may confirm the diagnosis of posterior tibial nerve entrapment.
      CONCLUSIONS: Peripheral nerve entrapment should be considered in patients with
      Baker's cysts and loss of sensation along the plantar aspect of the foot or other
      neurological symptoms or findings.

PMID- 9572710
TI  - Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved
      in toxicity.
AB  - OBJECTIVES: To provide an update of the current knowledge of the mechanism of
      action of low-dose methotrexate (MTX) in the treatment of patients with
      rheumatoid arthritis (RA), with an emphasis on the mechanisms involved in
      toxicity. We also considered strategies currently used to prevent or decrease
      toxicity of MTX. METHODS: We reviewed the literature dealing with the subjects of
      MTX treatment of RA, the mechanisms of action of low-dose MTX regarding efficacy
      and toxicity, and strategies used to prevent or decrease MTX toxicity. RESULTS:
      MTX is a fast working and effective second-line antirheumatic agent (SLA). Its
      use is limited mainly because of side effects. The mechanisms of action regarding
      efficacy and toxicity are probably determined by different metabolic pathways.
      Recent data indicate that the antiinflammatory effect of MTX is mediated by
      adenosine. However, MTX side effects can only partly be explained by folate
      antagonism and may also depend on its action on other related metabolic pathways.
      The latter include the homocysteine-methionine-polyamine pathway and purine
      metabolism. Variants in these metabolic routes (ie, the C677T mutation in the
      methylene-tetrahydrofolate reductase [MTHFR] gene), may predispose to the
      development of side effects. Currently the most promising strategy to decrease or
      prevent toxicity of MTX is concomitant prescription of folic acid or folinic
      acid. Other strategies are currently under investigation. CONCLUSIONS: MTX
      benefits a majority of RA patients. Approximately 30% of patients, however,
      abandon treatment because of drug-related side effects. Folic acid or folinic
      acid likely reduces MTX toxicity. More data, however, are needed to evaluate a
      potential detrimental effect on the antirheumatic efficacy of MTX.

PMID- 9572711
TI  - Reiter's syndrome among Asian shipboard immigrants: the case of The Golden
      Venture.
AB  - OBJECTIVE: To assess the incidence of Reiter's syndrome aboard The Golden
      Venture, a ship carrying illegal immigrants from China to the United States.
      METHODS: After identification of an index case, we conducted telephone interviews
      with medical staff at immigrant detention centers in Pennsylvania, New York, and
      Virginia. When a potential case was identified at one facility, we performed a
      site inspection, reviewing the medical records of all detainees and performing
      histories and physicals on all those with joint and/or ocular complaints.
      RESULTS: We identified two patients, both HLA B27 positive, with Reiter's
      syndrome. The observed incidence (0.87%) approximated the predicted incidence but
      may have underestimated the actual incidence. We review the history of shipboard
      Reiter's syndrome, and discuss the pathogenic roles of HLA B27 and particular
      infectious agents. CONCLUSION: Continued transportation of illegal immigrants
      from China and other parts of the world is likely to result in occasional
      clusters of Reiter's syndrome. Physicians treating immigrant populations should
      remain aware of the possibility of reactive arthritis.

PMID- 9572712
TI  - Progressive sensorineural hearing impairment in systemic vasculitides.
AB  - OBJECTIVES: A large series of patients with various forms of systemic vasculitis
      were evaluated to analyze the prevalence of progressive sensorineural hearing
      loss (PSNHL), its characteristics and evolution, and the effects of different
      therapies. METHODS: A total of 673 patients were questioned about the presence of
      subjective audiovestibular disturbances. Of those, 80 subjects complained of
      subjective audiological disturbances and underwent oto-rhino-laryngological and
      audiovestibular evaluation. Those patients with progressive hearing impairment
      were selected and studied carefully. RESULTS: A PSNHL was observed in 14
      patients. The hearing loss was bilateral and asymmetrical in most subjects. It
      was usually sensorineural, with a cochlear lesion. Unsteadiness was the most
      frequent vestibular symptom and canal paresis or palsy was noted in most
      patients. Systemic corticosteroids and cyclophosphamide were useful treatments;
      in unresponsive patients, satisfactory results were obtained with methotrexate
      and plasma exchange. CONCLUSIONS: PSNHL is a rare complication of systemic
      vasculitis, but occasionally is one of the presenting symptoms. Its clinical
      evolution is variable, but timely clinical assessment and treatment can
      positively affect prognosis.

PMID- 9572713
TI  - High incidence of malignancies in patients with dermatomyositis and polymyositis:
      an 11-year analysis.
AB  - OBJECTIVES: Dermatomyositis and polymyositis (DM/PM) are associated with
      neoplasms. The aim of the present study is to compare our experience in Israel
      with other published data. METHODS: Thirty-five adult patients with DM/PM,
      admitted to Sheba Medical Center during the 11-year interval between 1984 and
      1994, were studied for the prevalence and features of malignant diseases.
      Patients with DM/PM alone and with DM/PM and malignancy were identified by using
      the hospital computer system. The manifestations of DM/PM and features of the
      malignant diseases were abstracted from the patients' charts. The presence or
      absence of malignancy and the type of cancer were verified in the National Cancer
      Registry. RESULTS: There were 15 men and 20 women. The mean age at the onset of
      the disease was 53 +/- 18 years. A total of 15 had PM and 20 DM. Malignancies
      occurred in four patients with PM (27%) and in nine with DM (45%) a frequency
      12.6 times higher than in the general population. In six patients, the malignancy
      and the DM/PM were diagnosed simultaneously; in four before and in three after
      the appearance of the DM/PM. Hematologic, gastrointestinal, breast, ovarian, and
      lung tumors, malignant melanoma, and metastatic carcinoma of unknown primary were
      found among our patients. Eight DM/PM patients with malignancy died during the
      study period of infection, pulmonary embolism, and tumor spread. CONCLUSIONS: Our
      study found that DM/PM is associated with high rates of malignancy and mortality.

PMID- 9572714
TI  - Epidemiology of rheumatoid arthritis in Finland.
AB  - OBJECTIVES: To review the work pertaining to rheumatoid arthritis (RA) morbidity
      in Finland and to compare the data with that available from other countries.
      METHODS: Extensive investigations in Finland of the epidemiology of RA, based on
      nationwide registers designed primarily for administrative purposes and on
      extensive population studies, frequently in combination. RESULTS: According to
      several surveys with somewhat different study designs, the prevalence of
      clinically significant RA is about 0.8% of the adult Finnish population. Five
      national health interviews from a 30-year period have revealed figures about 50%
      higher, but with no clear change in prevalence. The incidence of clinically
      significant RA is about 40 per 100,000 of the adult population, which is in
      accordance with the prevalence figures. The mean age at diagnosis increased by
      7.6 years from 1975 to 1990. Between 1978 and 1980, 5.8% of the severe disability
      in the adult Finnish population was attributable to RA. Some evidence suggests
      that severe disability resulting from RA diminished during the 1980s, possibly
      because of joint replacement surgery. CONCLUSIONS: Monitoring sickness insurance
      statistics is a useful means of following the epidemiology of RA.

PMID- 9572715
TI  - Comparisons of head direction cell activity in the postsubiculum and anterior
      thalamus of freely moving rats.
AB  - Single cells in the rat anterior thalamic nucleus (ATN) and postsubiculum (PoS)
      discharge as a function of the rat's directional heading in the horizontal plane,
      independent of its location. A previous study that compared cell firing during
      clockwise and counterclockwise head turns concluded that ATN 'head direction'
      (HD) cell discharge anticipates the rat's future directional heading, while PoS
      HD cell discharge is in register with the rat's current directional heading
      (Blair and Sharp [1995] J Neurosci 15:6260-6270). In the current study we extend
      these findings by using a different method of analysis. HD cells in the ATN and
      PoS were first characterized by three different measures: peak firing rate, range
      width, and information content. We then examined how these measures varied when
      cell firing was aligned with past (negative time shift) or future (positive time
      shift) head direction of the rat. We report that all three measures were
      optimized when ATN cell firing was aligned with the animal's future directional
      heading by about +23 msec. In contrast, PoS HD cell firing was optimized when
      cell firing was aligned with the rat's past head direction by about -7 msec. When
      the optimal value was plotted as a function of the amount of time spikes were
      shifted relative to head orientation, the mean ATN function was shifted to the
      right of the PoS function only at negative time shifts; at positive time shifts
      the two functions overlapped. Analysis of two recording sessions from the same
      cell indicated that each cell in a particular brain area is 'tuned' to a specific
      time shift so that all cells within a brain area are not uniformly tuned to the
      same time shift. Other analyses showed that the clockwise and counterclockwise
      tuning functions were not skewed in the direction of the head turn as postulated
      by Redish et al. ([1996] Network: Computation in Neural Systems 7:671-685) and
      Blair et al. ([1997] J Neurophysiol 17:145-159). Additional analysis on episodes
      when the rat happened to continually point its head in the preferred direction
      indicated that HD cell firing undergoes little adaptation. In the Discussion, we
      argue that these results are best accounted for by a motor efference copy signal
      operating on both types of HD cells such that the copy associated with the PoS HD
      cells is delayed in time by about 30 msec relative to the copy associated with
      ATN HD cells.

PMID- 9572716
TI  - Baclofen infused in rat hippocampal formation impairs spatial learning.
AB  - Recent studies show that baclofen, a selective GABA(B) agonist, impairs different
      kinds of learning. In the present study we investigated the effect of
      microinfused baclofen into the hippocampus of male Wistar rats, on the
      performance in the Morris water maze. Rats of 8-10 weeks of age were implanted
      with cannulae aimed bilaterally at the hippocampal formation. Baclofen (1 microl
      of 0.2 mM, 2.0 mM, and 20.0 mM) or sterilized saline was microinfused 1 h before
      each daily session (3 trials/session, 1 session/day) for 4 days. On the fifth
      day, the animals did not receive drug or saline injections and the retention of
      the location of the escape platform was tested in a 30 s free swim trial. Results
      from the free swim trial indicate that the doses of baclofen used during training
      affected the ability of the rats to swim to the target quadrant. Although no
      significant difference compared with the saline group was observed, the
      experimental rats showed a more generalized swim trajectory in the area of the
      target and both adjacent quadrants. Moreover, 1 microl of 20.0 mM baclofen also
      impaired the acquisition. We suggest that baclofen has an impairing action on
      spatial learning, although more studies should be conducted to reach a more
      precise conclusion.

PMID- 9572717
TI  - Lesions of perirhinal cortex produce spatial memory deficits in the radial maze.
AB  - Rats with bilateral electrolytic lesions of perirhinal cortex (PRC) or sham
      control (SHAM) lesions were tested in spatial reference and working memory tasks
      in the radial arm maze. In experiment 1, one arm of the maze was baited and
      always located in a fixed position relative to the extra-maze environment. PRC
      lesioned animals made a significantly greater number of errors than did SHAM
      animals during initial training in this reference memory task and exhibited a
      delay-dependent impairment on trial 5 in a series when a delay period of 5, 60,
      120, or 240 s was inserted between trials 4 and 5. In experiment 2, when a second
      group of the animals was tested on the standard radial arm maze working memory
      task, the performance of the PRC group was markedly impaired relative to
      controls. These data demonstrate that electrolytic PRC lesions result in a
      deficit in both spatial reference and spatial working memory tasks. These effects
      are interpreted as being consistent with the idea that PRC plays an important
      role in episodic memory processes. These processes may include the storage of
      information, which is required for the performance of spatial tasks.

PMID- 9572718
TI  - Spatial mapping takes time.
AB  - The experiment tested the prediction that spatial mapping takes time and asked
      whether time use is reflected in the overt behavior of a performing animal. The
      study examines this question by exploiting the expected behavioral differences of
      control rats and rats with hippocampal formation damage induced with fimbria
      fornix (FF) lesions on a spatial navigation task. Previous studies have shown
      that control rats use a mapping strategy, in which they use the relative
      positions of environmental cues to reach places in space, whereas FF rats use a
      cue-based strategy, in which they are guided by a single cue or their own body
      orientation. Therefore, control and FF rats were overtrained on a complex
      foraging task in which they left a burrow to retrieve eight food pellets hidden
      around the perimeter of a circular table. The control rats retrieved the food
      pellets in order of their distance from the burrow, took direct routes to the
      food, and made few errors, all of which suggested they used a spatial strategy.
      The FF rats were less likely to retrieve food as a function of its distance, took
      a circular path around the perimeter of the table, and made many errors,
      suggesting they used a cue-based strategy. Despite taking shorter routes than the
      FF rats, the control rats had proportionally slower response speeds. Their slow
      response speeds support the hypothesis that spatial mapping takes time and that
      mapping time is reflected in behavior. The results are discussed in relation to
      their relevance to spatial mapping theory, hippocampal function, and the
      evolution of foraging strategies.